Wheat toxicity

And btw...STOP WHEAT In polyglandular autoimmune thyroiditis (hypothyroidism), melatonin levels were naturally found to be low particularly when more fatigue was observed by the study participants. The more fatigue, additionally, the more auto-antibodies were found associated with more organs. The adrenals were attacked in addition to the ovaries, thyroid and/or TPO (thyroid peroxidase). It is not clear precisely the relationship between thyroid function, melatonin and auto-antibodies here... In trials looking at simple hypothyroidism, often melatonin levels are fine or mildly shifted. In the case where multiple glands/organs are affected, the melatonin effects appear more significant. I never realized we could make auto-antibodies to our adrenals. But the medical literature is chock full of stories of auto-antibodies produced against nearly ANYTHING in our bodies -- including our p450 enzymes and even...(!!) mitochondria (our little nuclear ATP powerhouses). ??Can we possibly produce auto-antibodies to our pineal? Or calcify it to rock or pebble? Why not? I believe we could... Wheat as you aware is not only a common food allergen, but it increases gene expression (62 in this trial detected) of a variety of stress hormones, cytokine-chemokinemediated immunity, and the interleukin pathway, and MMPs (metalloproteinases) (prior post on the FUNGENUT study). Does wheat trigger the increased production of auto-antibodies? Absolutely. Hypothyroidism is a common autoimmune manifestation of silent celiac disease, in other words wheat intolerance. Other organs or tissues frequently 'burnt to a toast' include: Fingers/Rheumatoid; Wrists/CTS; Knees/osteoarthritis; Gallbladder/biliary dz; Insulin receptors/Type 2 Diabetes; Pancreas/Type 1 Diabetes; Ovaries/infertility; Spit glands/Sjogrens; Myelin/MS; et cetera. How about Muscles/fibromyalgia? The Brain?? Consideration of complete wheat cessation is necessary I believe to prevent burning out multiple organs (including the coronary vasculature). [The fatigue syndrome in autoimmune thyroiditis with polyglandular activation of autoimmunity][Article in Czech] Zamrazil V et al.Vnitr Lek. 1998 Aug;44(8):456-60. The authors compared in a group of 118 patients with autoimmune thyroiditis and a positive antibody titre against ovaries the grade of fatigue with the presence of organ specific and nonspecific autoantibodies in the peripheral blood stream, antibodies against EBV and CMV, immunoglobulin concentrations, biochemical parameters of the lipid metabolism, glucose tolerance, ion balance and melatonin and serotonin levels. Patients with autoimmune thyroiditis were differentiated according to the degree of fatigue into three groups: 38 with fatigue typical for CFS (chronic fatigue syndrome), 30 with occasional fatigue and 50 without the feeling of

fatigue. Fatigue of the CSF type was characterized by a significantly higher incidence of autoantibodies against the adrenals and a higher cholesterol level. Increased fatigue of the patients was associated with a lower melatonin level, a higher serotonin level and a lower M/S ratio as compared with patients without fatigue. In other indicators no differences were found. Fatigue in CFS could be associated, similarly as in autoimmune endocrinopathies, with impaired immunoendocrine regulation. In autoimmune thyroiditis, regardless of the concomitant presence of fatigue, in addition to antibodies against thyroid peroxidase most frequently antibodies against the ovaries were detected. PMID: 10358448

Modern Wheat: Staff of Life or... Staff of Cancer? Death?

Admittedly, stopping wheat was the last part of TYP regimen that I embraced. It's also perhaps the H-A-R-D-E-S-T. Wheat is ubiquitious as a convenient and delicious food component (which makes up the largest tier of the USDA food pyramid and a half-tier of the Harvard healthy eating pyramid). Don't we need wheat for life? Well, after nearly one month now of (near) complete wheat cessation (cheated with 1-2 chocolate croissants aaannnnddd... a few beers, irresistible bread pudding and slices of Ezekiel), I have to say, there is life after wheat. No one died. No one had seizures or delirium tremens. No one even puked. Now my kids are a different story -- they still occasionally whine when they don't get their pizza, PB&J or penne pasta from Pasta Pomodoro, our (former) favorite restaurant. It turns out that potential replacements do exist (on earth)! Whole Foods Market (aka $$$ 'Whole WALLET') does have a gluten-free pizza shell in the frozen gluten-free area that is purportedly tasty. Rice noodles or mung bean noodles just are the same as penne pasta . . . How about a suitable vehicle for peanut butter & jelly. . . ? we're still figuring that out... any thoughts are welcome! Why are Wheat-grains so filthy and abominable in the Track Your Plaque plan for atherosclerosis stabilization and regression? Sounds so blasphemous doesn't it? Like cursing food of the gods? Wheat helped potentially grow the Roman empire (by supplying their soldierclass with a convenient portable energy source) and build world wonders like the Egyptian pyramids 3rd century BC. In modern times, why does it represent so many chronic diseases and ailments? Wheat is currently linked to all the below conditions. Acute sudden death does not generally occur (nor does anaphylaxis or other fatal reactions like scurvy or beri beri) however the death is chronic, very very slow, mildly painful, taking decades. --celiac sprue --'silent' celiac sprue --autoimmune diseases -- most arthritis syndromes (?even OA/DJD), Type 1 diabetes, Hashimoto's hypothyroidism, Grave's hyperthyroidism, lupus, multiple sclerosis, ?asthma --infertility --PCOS --NASH/NAFLD

--gallbladder disease --primary biliary --lymphoma --colon cancer --pancreatic cancer, other cancers --eczema, acne, psoriasis --systemic inflammation --et cetera Can our daily bread be causing cancer? People are in disbelief that the staff of life can be the strongest factor in (!!) infertility and crippling arthritis... 'Don't we need fiber?' as if I've suggested something sacreligious. 'Aren't we supposed have whole grains at every meal?' I used to feel the same way too until I was witness to testimonials. I'm more of a true believer now for complete wheat cessation after hearing not only amazing stories that Dr. Davis has frequently blogged about at HEARTSCANBLOG but witnessing some personal amazing stories from people who have stopped wheat completely in their lives for only 2 to 4 weeks.

decrease or elimination of 30-50 units insulin daily reduction in pain from arthritis decrease or cessation of pain and arthritis medications improvement in vitality, energy and youthfulness acne improvement or resolution skin showing glowing clarity and smoothness, eczema-free easy weight loss 10-15 lbs (women) or 20-30 lbs (men who typically start with more lean tissue mass than women) chronic pain syndromes improvement in neuropathic pain syndromes hypertension decrease or normalization

Many parts of the TYP plan promote heart protection as well as cancer prevention. Wheat cessation is just one part of this ultimate optimum health guarantee. Other critical components which clinical studies have shown to promote prevention and regression of cancer include: --fish oil omega-3 PUFAs EPA + DHA (high dose and ultra high dose) --elimination of pro-inflammatory omega-6 polyunsaturated fatty acids (cheap industrial veggie oils like safflower, sunflower, cottonseed, canola, etc) --excessive fructose (the carb in fruit and starches like corn) --elimination of trans fats and fructose/high-fructose-corn-syrup --normalization and optimization of steroid hormones: vitamins A/D/E/K2, B-complex, C, micronutrients (Zn, MAGNESIUM, Se, Cu, etc), Estrogen, Progesterone, Testosterone, DHEA, Thyroid, et cetera --daily exercise/movement/play + occasional intensive bursts ('sex' counts!)

--OPTIMISM Wheat, the staff of slow painful death... and cancer. Stop wheat products now for elite health and fitness. Consider trying wheat cessation for 1-2 wks -- you may be surprised by the results just as I was!

Eden: Liver = Heart

HOOVERPHONIC: Eden

Which Samurai with his spunky spiky haired-side kick deftly defeats PLAQUE?

Eating is definitely a sensory activity that starts with the brain-- have you heard that saying 'eating with your eyes'? Have you ever given your liver much thought while you consuming your meals or snacks? Ever wonder where does the food go before it hits the bloodstream? In fact, the human liver is the largest internal organ comprising of 3 lobes and receives all the blood after a meal from the stomach and intestines via the portal vein. How does the body sense abundance in the environment? Through the eyes? No... ye ol' LIVER... If food (quantity and quality and composition) serves as one of the cues from our external physical environment, then the liver and the PPAR receptors located there there are the sensors of the degree of energy abundance/scarcity. What elements are essential for life outside of air? Food -- water -- light.... Similarly, what senses light? It is likely that VDR (vitamin D receptor) plays an equally important and parallel role. Abundant sunlight for most countries near the equator typically signals abundant food/energy. Vitamin D does rev up energy, productivity, and *hey* fertility! Naturally it follows that the skeletal muscles are the sensor for muscle movement and certainly the PPAR receptors in skeletal muscle do a great deal to command the balance of energy demand and supply/thermogenesis.

What might the holy trinity of human energy look like? mTOR--PPAR--VDR ? How might it have been shaped in our 'evolutionary heritage'...??? (thanks for the term Grey Whale!) Well, we certainly know a lot of about what contribute's to this trinity's dysregulation... 1. Lean-muscle-and movement-deficiency 2. Wheat/grains consumption (including excessive fruit/FRUCTOSE too) 3. Vitamin D3/sunlight deficiency

Even statins improve this trinity... by activating (!!) PPAR ... This special antiinflammatory and MMP-stabilizing effect occurs specifically at the macrophage level and for plaque, this translates directly to the surface, volume and core of plaque atheroma. The pleiotropic benefits of statins can now be attributed to a direct activation of PPAR on macrophages via the MAPK pathway.

Paumelle R, Staels B. Peroxisome proliferator-activated receptors mediate pleiotropic actions of statins.Circ Res. 2007 May 25;100(10):1394-5. No abstract available. (see Diagram: Cross-talk of statins/ PPARs in the antiatherogenic properties of statins -- PDF here) PMID: 17525375 Yano M, Matsumura T, et al. Statins activate peroxisome proliferator-activated receptor gamma through extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase-dependent cyclooxygenase-2 expression in macrophages. Circ Res. 2007 May 25;100(10):1442-51. PMID: 17463321 Paumelle R, Staels B, et al. Acute antiinflammatory properties of statins involve peroxisome proliferator-activated receptor-alpha via inhibition of the protein kinase C signaling pathway. Circ Res. 2006 Feb 17;98(3):361-9. PMID: 16397146 Landrier JF, Thomas C, et al. Statin induction of liver fatty acid-binding protein (L-FABP) gene expression is peroxisome proliferator-activated receptor-alpha-dependent. J Biol Chem. 2004 Oct 29;279(44):45512-8. PMID: 15337740 Verreth W, De Keyzer D, et al. Rosuvastatin (INCREASES mRNA of PPAR-GAMMA AND) restores superoxide dismutase expression and inhibits accumulation of oxidized LDL in the aortic arch of obese dyslipidemic mice. Br J Pharmacol. 2007 Jun;151(3):347-55. PMID:

17384667 Roglans N, Sanguino E, et al. Atorvastatin treatment induced peroxisome proliferatoractivated receptor alpha expression and decreased plasma nonesterified fatty acids and liver triglyceride in fructose-fed rats. J Pharmacol Exp Ther. 2002 Jul;302(1):232-9. PMID: 12065722 Sanguino E, Roglans N, et al. Atorvastatin reverses age-related reduction in rat hepatic PPARalpha and HNF-4. Br J Pharmacol. 2005 Aug;145(7):853-61. PMID: 15912134

In historical texts (ie, the Bible), the liver was actually considered 'the heart.' And, in the ancient days, harm to the liver was actually worse than to the heart. How were they so wise (without high tech ALT/AST tests or abdominal u/s) ??! For warriors, the liver was an easier, bigger target to hit than the smaller heart. We often neglect this fantastic vital organ. Interestingly, when the trinity is disrupted, this organ becomes metabolically deranged even before the heart.

Here are the liver's awesome functions and roles:

first pass effect = all blood during digestion is maximized to flow through the liver. Perhaps this is the role after meal apertifs, Greek grappe or (!! YUM)aged port have -- they relax, increase Vagal communications to the GI system to further shunt blood flow to the stomach and intestines for digestion

cytochrome P450 -- detox's, purifies everything we eat including plant toxins and exogenous chemicals like drugs (explains why oral estrogen can worsen HDLs whereas topical/transdermal estrogen improves and RAISES HDLs by bypassing the liver route)

cytochrome P450 activates and processes everything we eat including all food components and neutraceuticals (vitamin D3, essential fatty acids, protein)

energy sensor (carbs, fats, proteins, alcohol, caffeine, etc -- all my favorite food groups)

ultimate CONTROLLER in the financial as well as airtraffic sense because the liver contains the highest concentration of PPAR receptors: alpha, gamma, and D-E-L-T-A (aka beta)

producer of lipoproteins which are the energy 'traffickers' for the immune system, skeletal muscles and even brain (which relies on ketones/fatty acids when blood glucose (BG) is naturally lower)

producer of TGs -- the lipoprotein fraction where carbohydrate-energy (dietary carb +/- fat) is bundled into for transport to the rest of the body (including clogging up the heart tissues and arteries). Recall that TGs is the second RISK FACTOR most highly associated with plaque. First is... fasting insulin levels.

regulates and synthesizes cholesterol which is the template of EVERY nuclear steroid (and some aromatases, desaturases, and cyt P450 are under the control of VitaminD3) -- steroids like testosterone, estrogen, cortisol -- and composes the structural backbone/shell of every cell in our body and in particular the brain/nervous system which is comprised nearly entirely of cholesterol and fats (should pregnant moms eat 'low fat'? do pregnant moms want braindeficient, cognitively-challenged children?)

vitally crucial for producing mannose-binding lectin (MBL) which is an activator of our host defenses in the innate broad-spectrum non-specific immune system (which fights virus, bacteria, and other foreign invaders including FRUCTOSE attached to our own cells) ; 'fruct-osylated-cells' aint good... sounds pretty bad eh? indeed VERY BAD

first organ to become unhappy when carbohydrates are excessive ('fatty liver', NAFLD, NASH, etc); see diagram above

one of the most prized organ meats and delicacy (in indigenous cultures and our household with a little soy sauce and honey) highly valued for its nutritional content of metabolically-active and heart protective Vitamins K2, D3, A, E and other essential nutrients and minerals.

In a recent Circulation article, researchers are elucidating the important role of Von Willebrand factor (VWF) in acute coronary syndromes (ACS).
"von Willebrand factor (VWF) plays a pivotal role in platelet adhesion and aggregation at sites of high shear rates (eg, in coronary arteries that have stenotic or ruptured atherosclerotic plaque lesions). Numerous studies have investigated the relationship between VWF plasma levels and thromboembolic cardiovascular events. In contrast to the rather weak association in the general population, in patients with preexisting vascular disease, VWF is significantly predictive for adverse cardiac events, including death. Likewise, VWF typically rises during the course of acute coronary syndrome, and the extent of this VWF release is an independent predictor of adverse clinical outcome in these patients. Various lines of evidence indicate that VWF is not only a marker but also actually an important effector in the pathogenesis of myocardial infarction. This central role of VWF in thrombogenesis has made it a promising target for research into new antiplatelet therapies that specifically inhibit VWF (AND BLAH BLAH BLAH... DRUGS)..."

How is VWF related to the thrombosis and clotting effects in our blood vessels? Obviously there is a healthy balance. Those with VWF deficiency have bleeding gums, mucus membranes and bleeding under the skin. Is the liver involved? It appears the liver is involved in everything! Platelets require the intervention of a blood protein known as Von Willebrand factor (vWF), which facilitates platelet adhesion to the sub-endothelial matrix of damaged, exposed endothelium. When the liver is aged, i.e. metabolically/oxidatively affected, a corresponding increase in vWF occurs intrahepatically (see below). Can this also occur systemically? To the coronary arteries? Or carotids? If we keep the endothelium of one of our most vital organs, the liver, happy... clear and uncongested, then endothelium elsewhere is likely to be protected as well. Prevent hardening of the liver, and you'll prevent hardening of the arteries. Reverse liver damage, and you'll reverse artery damage. Timing as usual makes a difference. Even young-obese children are displaying NASH/NAFLD and early changes in myocardial structure such as diastolic dysfunction/heart failure. The below changes including the increase in vWF from the endothelium in the liver blood circulation sounds a lot like instigation of arteriosclerosis of the liver...

Love your liver... and both hearts will appreciate it... Ways to maximize liver function and productivity: ** Movement, play, movement, work, intervals of intensity, play, grow your muscles... especially with our children. 'The family that plays together, stays together...and doesn't have heart attacks together,' quoted by a member at my CF gym ** Complete Wheat/Grain avoidance and minimal fruit ** Adequate vitamin D3 (achieve: 25(OH)D 60-70 ng/ml) Old age and the hepatic sinusoid. Anat Rec (Hoboken). 2008 Jun;291(6):672-83. Le Couteur DG, et al. Morphological changes in the hepatic sinusoid with old age are increasingly recognized. These include thickening and defenestration of the liver sinusoidal endothelial cell, sporadic deposition of collagen and basal lamina in the extracellular space of Disse, and increased numbers of fat engorged, nonactivated stellate cells. In addition, there is endothelial up-regulation of von Willebrand factor and ICAM-1 with reduced expression of caveolin-1. These changes have been termed age-related pseudocapillarization (SOUNDS TO ME LIKE CALCIFICATIONS AND ARTERIOSCLEROSIS). The effects of old age on Kupffer cells are inconsistent, but impaired responsiveness is likely. There are functional implications of these aging changes in the hepatic sinusoid. There is reduced sinusoidal perfusion, which will impair the hepatic clearance of highly extracted substrates. Blood clearance of a variety of waste macromolecules takes place in liver sinusoidal endothelial cells (LSECs). Previous studies indicated either that aging had no effect, or reduced the endocytic capacity of LSECs. However, a recent study in mice showed reduced endocytosis in pericentral regions of the liver lobules. Reduced endocytosis may increase systemic exposure to potential harmful waste macromolecules such as advanced glycation end products. Loss of fenestrations leads to impaired transfer of lipoproteins from blood to hepatocytes. This provides a mechanism for impaired chylomicron remnant clearance and postprandial hyperlipidemia associated with old age. Given the extensive range of substrates metabolized by the liver, age-related (I.E. METABOLIC DEREGULATION) changes in the hepatic sinusoid and microcirculation have important systemic implications for aging and age-related diseases. PMID: 18484614

Wheat: Raises Insulin and Upregulates 'Bad' Genes

Can our food alter gene expression?

Absolutely so! As Hippocrates once said, 'Let food by thy Medicine... and Medicine thy Food.' I'm sure he didn't mean medications as they exist now as chemicals or benzene rings (derived from petroleum) mass synthesized in factories for global consumption. The below FUNGENUT study recently showed the importance of how different sources of carbohydrate containing foods immediately changes gene expression in our favorite organ -- the omentum -- the stubborn fat lying on our bellies -- yes, the one covering up your those fabulous 6-pack abs. (Diagram: Ludwig, D. (2002) JAMA ) In a small group of subjects, 2 diets (Rye-Pasta -- mildly lower in GI; Oat-WheatPotato -- high GI carbs) were compared for 3 months. At the end no change in weight or insulin resistance, insulin levels, or glucose concentrations occurred. The profile for insulin (1st phase) secretion mildly improved in the Rye-Pasta group. Interestingly, other than showing that wheat sucks (and perhaps oat and potato) gene expression was entirely affected by simple changes in carbohydrate content and the Glycemic Index (GI measures how long and how fast glucose enters the blood stream after consumption). Rye (endosperm) bread has a GI (glycemic index) of approximately 60-70. Pasta's GI is about 60-70 as well (depending on the type and how al dente/not-overcooked).

Wheat bread on the other hand is about 90-100 (close to pure glucose). Oats about 70 and potatoes 80-100 (without cream or butter which slows the uptake of starches into the stomach blood circulation which would effectively lower the GI). American Russet potato even exceeds glucose, 110 (!wow).

CARBOHYDRATE COMPOSITION OF FOOD PROVIDE MOLECULAR EFFECTS AND LOWGI CARBS DOWNREGULATE 'BAD' GENES: "Prior microarray studies found differences in gene expression between overweight and lean individuals (2) and after energy restriction (3); however, changes in the ratio of fat to carbohydrate did not alter gene expression (3). The study by Kallio et al makes a significant contribution to the literature by demonstrating the potentially major effects of dietary composition on gene regulation, independent of energy intake and body weight. Two specific findings concerning the low-insulin-response diet merit particular attention: the down-regulation of both hormone-sensitive lipase (HSL) and TCF7L2. " "HSL, a key enzyme in the release of fatty acids from adipose tissue, has been

proposed to affect body weight and metabolic variables. Mice made deficient in HSL by genetic manipulation are resistant to genetic- or diet-induced obesity (4, 5). Women carrying an allele associated with decreased HSL activity have lower fasting and simulated insulin concentrations, and men with this allele have lower nonesterified fatty acid concentrations (6)..." "The transcription factor TCF7L2 is the strongest known genetic predictor of type 2 diabetes. A microsatellite within intron 3 of this transcription factor occurs with increased frequency in individuals with type 2 diabetes, which corresponds to an estimated population attributable risk of 21% (7)..." "The present study (BELOW) has direct implications concerning our understanding of the dietary glycemic index (GI). The GI is a system for classifying carbohydratecontaining foods according to how blood glucose concentrations change in the postprandial period (reviewed in reference 8). High-GI meals produce greater postprandial insulin concentrations and C-peptide excretion than do nutrientcontrolled low-GI meals. Observational and interventional studies have linked GI to the risk of obesity, diabetes, heart disease, and cancer, although the topic remains much debated. One factor contributing to this ongoing controversy is the relative paucity of data regarding the relevant molecular mechanisms. If differences in insulin secretion mediate the genetic effects observed by Kallio et al, similar effects would be expected to occur with both low-GI and high-GI diets. This possibility is supported by a human study and several rodent studies, which showed potentially beneficial changes in the expression of HSL and other relevant genes with a low-GI diet (8, 9)." Contrastingly, the high-GI wheat (+oat+potato) diet upregulated 62 genes including those associated with: -- Stress -- Oxidative damage -- Impaired immunity So... high carb diet translates to... the equivalence of a STRESS RESPONSE. The authors discuss in more depth the results from the FUNGENUT Study..."Interestingly, the 12-wk oat-wheat-potato diet seemed to especially activate genes responding to stress. The oxidative stress pathway, interleukin pathway, and inflammation mediated by the chemokine and cytokine signaling pathway were also activated. Moreover, the present data suggest that the oatwheat-potato diet, which induced repeated high insulin responses, can provoke alterations in immune status and inflammation. It is well established that adipose tissue has a role in inflammation (39). Cross-sectional epidemiologic data suggest that whole grains and a low-glycemic-index diet may reduce systemic inflammation in women with T2DM (40). Up-regulation of gene expression for serum and

glucocorticoid-regulated kinase suggests activation of the glucocorticoid axis, which can occur in response to various stress stimuli (cytokines, aldosterone, growth factors, oxidative stress, heat shock protein activation, and glucocorticoids) (41). Activation of the pituitary-adrenal glucocorticoid axis may be involved in the pathogenesis of the metabolic syndrome (42)."
Dietary carbohydrate modification induces alterations in gene expression in abdominal subcutaneous adipose tissue in persons with the metabolic syndrome: the FUNGENUT Study. Kallio P, et al. Am J Clin Nutr. 2007 May;85(5):1169-70. Department of Clinical Nutrition, Food and Health Research Centre, University of Kuopio, Kuopio, Finland. BACKGROUND: Diets rich in whole-grain cereals and foods with a low glycemic index may protect against type 2 diabetes, but the underlying molecular mechanisms are unknown. OBJECTIVE: The main objective was to test whether 2 different carbohydrate modifications-a rye-pasta diet characterized by a low postprandial insulin response and an oat-wheatpotato diet characterized by a high postprandial insulin response--affect gene expression in subcutaneous adipose tissue (SAT) in persons with the metabolic syndrome. DESIGN: We assessed the effect of carbohydrate modification on SAT gene expression in 47 subjects [24 men and 23 women with a mean (+/-SD) age of 55 +/- 6 y] with the features of the metabolic syndrome in a parallel study design. The subjects had a mean (+/-SD) body mass index (kg/m(2)) of 32.1 +/- 3.8 and a 2-h plasma glucose concentration of 8.0 +/- 2.3 mmol/L. Adipose tissue biopsies were performed, and oral-glucose-tolerance tests and other biochemical measurements were conducted before and after the intervention. RESULTS: We detected 71 down-regulated genes in the rye-pasta group, including genes linked to insulin signaling and apoptosis. In contrast, the 12-wk oat-wheatpotato diet up-regulated 62 genes related to stress, cytokine-chemokinemediated immunity, and the interleukin pathway. The insulinogenic index improved after the rye-pasta diet (P=0.004) but not after the oat-wheat-potato diet. Body weight was unchanged in both groups. CONCLUSIONS: Dietary carbohydrate modification with rye and pasta or oat, wheat, and potato differentially modulates the gene expression profile in abdominal subcutaneous adipose tissue, even in the absence of weight loss. PMID: 17490981

These wonderful graphs from Finland researchers illustrate how the toxic effects of grain sources of carbohydrates occur when wheat and rye are fed to healthy volunteers. Above a glucose blood concentration of 150 mg/dl (=8.3 mmol/L), glucose starts to cause changes in protein folding and glycosylating proteins and tissues. Diabetes micro-vascular complications like eye/kidney/nerve ending damage are related to toxic concentrations of glucose. Imagine sugar coating the organs over time. The higher the concentration, the longer the duration, the more thicker and more damaging the sugar coating. Insulin is controlled by several factors. Food is one of the most potent controllers, with carbohydrates and their respective GIs raising insulin levels the most. Excessive insulin induces in

flammation, which can progress and cause arterial stiffness, high blood pressure, Metabolic Syndrome, obesity, and also heart disease. Longevity has been associated with lower insulin levels. The below trial demonstrates the direct relationship in 18-year old men between fasting insulin and the existence of cardiovascular markers. The curves for low or no GI foods have no peaks and in comparison are relatively flat. Without a surge in insulin, inflammation is kept at bay. Foods with no or little GI: -- Non-starchy vegetables -- Protein (tofu, meat, fish, etc) -- Monounsaturated fat -- Omega-3 PUFA -- Saturated fat The Track Your Plaque goal for nearly all metabolic and cardiovascular goals is NORMAL. Therefore the optimal range for insulin is as low as possible less than 5 10 mIU/L. The goal for glucoses pre-meal is less than 83 (=4.6mmol/L) and after meals less than 110 to 120 (=6.1 to 6.67mmol/L).
Relationship between fasting insulin and cardiovascular risk factors is already present in young men: the Verona Young Men Atherosclerosis Risk Factors Study. Bonora E, et al. Eur J Clin Invest. 1997 Mar;27(3):248-54. The associations between fasting plasma insulin concentration and risk factors for cardiovascular disease were examined in 979 18-year-old men participating in the Verona Young Men Atherosclerosis Risk Factors Study, a cross-sectional population-based study. Body mass index (BMI), waist-to-hip ratio (WHR), plasma triglycerides and uric acid concentrations, and blood pressure values significantly increased, and the high-density lipoprotein (HDL)-total cholesterol ratio decreased, across quartiles of fasting insulin. Total and low-density lipoprotein cholesterol, concentrations did not change significantly with the increase in fasting insulin levels. After adjustment for BMI, WHR, smoking, alcohol intake and physical activity, only plasma triglycerides significantly increased across insulin quartiles (F = 7.1; P less than 0.001). However, systolic blood pressure and uric acid were close to statistical significance (P = 0.06-0.07). Multiple linear regression analysis confirmed that plasma insulin was independently correlated with plasma triglycerides and, to a lesser extent, with blood pressure and uric acid concentration. This analysis pointed out that BMI was a stronger independent predictor of all cardiovascular disease risk factors than fasting insulin. When subjects were categorized according to the number of metabolic and haemodynamic disorders occurring within the same individual, subjects with multiple disorders (i.e, three or four) had higher plasma insulin levels than those with none or few disorders, even after adjusting for BMI, WHR and behavioural variables (F = 4.0; P less than 0.01). These results indicate that hyperinsulinaemia is already associated with a cluster of cardiovascular disease risk factors in young adulthood, the strongest independent association being with plasma triglycerides. PMID: 9088862

Wheat: Is It Evil Or Just in the Context of Vitamin D and EPA+DHA Deficiency?

I love Gladiator (yes, it's one of my all time f-a-v-e movies, next to When Harry Met Sally)... the first scene is mesmerizing... he's watching the flax and wheat fields glowing with gold, fearless in the face of death. In the dawn of time, ancient wheat probably did not cause as many autoimmune and silent/non-silent celiac diseases (or ?autism or ?coronary artery disease) as the present day. Why? In the Gladiator days, for one, sunscreen did not exist! Secondly, most people worked and warriored outdoors. Toiling in the sun, hand laundering clothes, baking bread on outdoor hearths, practicing swordplay, gathering berries, fishing, preparing crops, hunting gamey-flesh (which BTW gamey-meat and grass-fed beef are enriched in EPA+DHA, much like fatty deep sea fish/fish oil), and other noble chores in the bright sunshine (because candles were scarce). All day long 24/7... Does having enough sunlight and vitamin D give us more power to tolerate gluten and not develop damaging self-destructive auto-antibodies? It's unlikely we'll know in any good RCT (randomized controlled trials). No drug company will put up lettuce $$ to determine that good ol' cheap FREE UVB unblocked-sunshine is going to trump their $2-3/day drug (or super-sized vitamin D analogue) in a head-to-head trial. That's just absurd. And they're not stupid... because they pay staticians a lot of lettuce to figure that out for them. Psoriasis is another celiac condition (incl autoimmune). What are the pharmacological treatments? UVB lightbox 5-10min weekly as needed and topical vitamin D derivatives in creams/ointments (and a couple of toxic Immunosuppressive injections like Enbrel for instance which has a side effect of c-an-c-e-r). New diagnostic techniques for celiac disease (widely used in Europe) are being employed now (check this out here). Years ago Dr. Davis figured out the value and power of oral administration of natural Vitamin D3. The recently published study impressively validates his work. Effective tratment: Vitamin D3 (+ gluten-free lifestyle/diet plan)
Am J Med. 1978 Dec;65(6):1015-20. Osteomalacia and celiac disease: response to 25-hydroxyvitamin D3. Hepner GW, Jowsey J, Arnaud C, Gordon S, Black J, Roginsky M, Moo HF, Young JF. In this 54 year old woman with celiac disease, osteomalacia developed while she was on a gluten-free diet which had caused regression of her steatorrhea. She was not responsive to large doses of parenterally administered dihydrotachysterol (fake foreign synthetic vitamin D version) and calcium, but she was responsive to the oral administration of

25-hydroxyvitamin D3 (25-OHD3 = natural). The data suggest that 25-OHD3 is the treatment of choice for patients with vitamin D deficiency due to intestinal malabsorption. PMID: 742623

Effective treatment: Fish oil! Fish oil has been shown to be hugely beneficial due to its impressive autoimmune immunemodulating and skin-stabilizing benefits. Anything anti-inflammatory helps (like antioxidants with high ORAC scores). Fasting creates lower systemic bodily inflammation -- yes the MONKS know what they are doing. In TYP, the practice of intermittent fasting is a fast way to success.
Br J Dermatol. 2005 Oct;153(4):706-14. Diet and psoriasis: experimental data and clinical evidence. Wolters M. Psoriasis is considered as a T-cell-mediated inflammatory skin disease which is characterized by hyperproliferation and poor differentiation of epidermal keratinocytes. While susceptibility to psoriasis is inherited, the disease is influenced by environmental factors such as infections and stress. Diet has been suggested to play a role in the aetiology and pathogenesis of psoriasis. Fasting periods, low-energy diets and vegetarian diets improved psoriasis symptoms in some studies, and diets rich in n-3 polyunsaturated fatty acids from fish oil also showed beneficial effects. All these diets modify the polyunsaturated fatty acid metabolism and influence the eicosanoid profile, so that inflammatory processes are suppressed. Some patients with psoriasis show an elevated sensitivity to gluten. In patients with IgA and/or IgG antigliadin antibodies the symptoms have been shown to improve on a gluten-free diet. The active form of vitamin D, 1,25dihydroxyvitamin D(3), exhibits antiproliferative and immunoregulatory effects via the vitamin D receptor (HOW ABOUT TAKING VITAMIN D3 ORALLY DAILY??), and thus is successfully used in the topical treatment of psoriasis. In this review, dietary factors which play a role in psoriasis are assessed and their potential benefit is evaluated. Furthermore, the risk of drug-nutrient interactions in psoriasis therapy is discussed (WHAT THEY'RE SAYING IS WHEAT-CESSATION IS KEY TO PREVENTING PROGRESSION AND TO REVERSING PSORIASIS). PMID: 16181450

(These are many of the same strategies in TYP of course)

Are all autoimmune conditions (including Grave's and the frequently diagnosed Hashimoto's thyroiditis) just silent or non-silent celiac disease? Why are wheat/gluten antibodies implicated so often? Why is Vitamin D deficiency and a lack of dietary EPA+DHA commonly associated with celiac conditions (and autism and coronary artery disease)? And improve these

conditions? Which came first? The chicken or the egg?? Does maternal health and in utero environments affect not only the fetus, but even the following generation as they do in rat experiments? At least TrackYourPlaque provides answers.... Including the below... --Optimize your vitamin D3 level (25)OHD = 60 ng/ml --Optimize your fish oil EPA + DHA 3000 mg daily (supplements + dietary fish, shellfish, pasture-fed protein -- see last study) (or more if you have elevated Lp(a) > 30 mg/dl) --Wheat-cessation program (yes.. that's all pasta, noodles, mac-n-cheese, bread, cereal, croissants (omg very hard), crackers, cookies, even soy sauce, etc) --Optimize optimism (vitamin 'O')

Clin Rheumatol. 2006 Mar;25(2):240-5. Association of systemic and thyroid autoimmune diseases.Bir E, Szekanecz Z, Czirjk L, Dank K, Kiss E, Szab NA, Szucs G, Zeher M, Bodolay E, Szegedi G, Bak G. OBJECTIVE: There are few large cohort studies available on the association of systemic and thyroid autoimmune diseases. In this study, we wished to determine the association of Hashimoto's thyroiditis (HT) and Graves' disease (GD) with systemic autoimmune diseases. METHODS: One thousand five hundred and seventeen patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc), mixed connective tissue disease (MCTD), Sjgren's syndrome (SS) and polymyositis/dermatomyositis (PM/DM) were included in the study. The HT and GD were diagnosed based on thorough clinical evaluation, imaging and fine-needle aspiration cytology (FNAC). The frequency of HT and GD in these diseases was assessed. In addition, 426 patients with HT or GD were assessed and the incidence of SLE, RA, SSc, MCTD, SS and PM/DM among these patients was determined. Prevalence ratios indicating the prevalences of GD or HT among our autoimmune patients in comparison to prevalences of GD or HT in the general population were calculated. RESULTS: Altogether 8.2% of systemic autoimmune patients had either HT or GD. MCTD and SS most frequently overlapped with autoimmune thyroid diseases (24 and 10%, respectively). HT was more common among MCTD, SS and RA patients (21, 7 and 6%, respectively) than GD (2.5, 3 and 1.6%, respectively). The prevalences of HT in SLE, RA, SSc, MCTD, SS and PM/DM were 90-, 160-, 220-, 556-, 176- and 69-fold higher than in the general population, respectively. The prevalences of GD in the same systemic diseases were 68-, 50-, 102-, 76-, 74- and 37-fold higher than in the general population, respectively. Among all thyroid patients, 30% had associated systemic disease. In particular, 51% of HT and only 16% of GD subjects had any of the systemic disorders. MCTD, SS, SLE, RA, SSc and PM/DM were all more common among HT patients (20, 17, 7, 4, 2 and 2%, respectively) than in GD individuals (2, 5, 5, 1, 2 and 1%, respectively). CONCLUSION: Systemic and thyroid autoimmune diseases often overlap with each other. HT and GD may be most common among MCTD, SSc and SS patients. On the other hand, these systemic diseases are often present in HT subjects. Therefore it is clinically important to screen patients with systemic autoimmune diseases for the co-existence of thyroid disorders. PMID: 16247581

Biomed Pharmacother. 2007 Feb-Apr;61(2-3):105-12. Dietary omega-3 fatty acids for women. Bourre JM. This review details the specific needs of women for omega-3 fatty acids, including alpha linoleic acid (ALA) and the very long chain fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Omega-3 fatty acid (dietary or in capsules) ensures that a woman's adipose tissue contains a reserve of these fatty acids for the developing fetus and the breast-fed newborn infant. This ensures the optimal cerebral and cognitive development of the infant. The presence of large quantities of EPA and DHA in the diet slightly lengthens pregnancy, and improves its quality. Human milk contains both ALA and DHA, unlike that of other mammals. Conditions such as diabetes can alter the fatty acid profile of mother's milk, while certain diets, like those of vegetarians, vegans, or even macrobiotic diets, can have the same effect, if they do not include seafood. ALA, DHA and EPA, are important for preventing ischemic cardiovascular disease in women of all ages. Omega-3 fatty acids can help to prevent the development of certain cancers, particularly those of the breast and colon, and possibly of the uterus and the skin, and are likely to reduce the risk of postpartum depression, manic-depressive psychosis, dementias (Alzheimer's disease and others), hypertension, toxemia, diabetes and, to a certain extend, age-related macular degeneration. Omega-3 fatty acids could play a positive role in the prevention of menstrual syndrome and postmenopausal hot flushes. The normal western diet contains little ALA (less than 50% of the RDA). The only adequate sources are rapeseed oil (canola; CAVEAT THIS ALSO CONTAINS OMEGA6'S WHICH IS PRO-INFLAMMATORY WHEN EXCESSIVE), walnuts and socalled "omega-3" eggs (similar to wild-type or Cretan eggs). The amounts of EPA and DHA in the diet vary greatly from person to person. The only good sources are fish and seafood, together with "omega-3" eggs. PMID: 17254747

Asia Pac J Clin Nutr. 2003.12 Suppl:S38 Feeding regimes affect fatty acid composition in Australian beef cattle. Mann NJ, Ponnampalam EN, Yep Y, Sinclair AJ. Background - There is growing evidence that red meat contributes significantly to the intake of omega 3 long chain PUFA in western diets. The type of feeding regime used in animal production, can influence the lipids in red meat due to the fatty acid composition of the feed. Pasture feed being relatively rich in a-linolenic acid (18:3 n3), while grain is relatively rich in linoleic acid (18:2n-6). Objective - To determine the effect on beef fatty acid profile of varying length of grain feeding compared with grass feeding. Design - Samples of rump, strip loin and blade cuts were obtained from eighteen

cattle from each of three feeding regimes (pasture fed, short term grain feeding STGF, and long term grain feeding LTGF). All samples were analysed in triplicate as lean tissue only, using a standard chloroform - methanol extraction and capillary column gas-chromatograph fatty acid quantification. Outcomes - Total fat, saturated and monounsaturated fatty acids were all significantly higher in the LTGF animals. The grass fed animals had higher levels of omega 3 PUFA in all three cuts, with combined EPA + DHA reaching levels in blade and strip loin that would meet Australian Food Standards classification as a ' source' of omega-3, with the rump cut reaching this level in the STGF group also. Rump from the grass fed animals was a relatively rich source of EPA + DHA and would qualify as a 'good source' of omega 3. Conclusions - This study was able to show that pasture feeding of Australian cattle maximises omega-3 PUFA content and minimizes trans 18:1 fatty acid levels relative to grain feeding. Furthermore, LTGF results in elevated total fat and saturated fat content relative to STGF or grass feeding in lean cuts of Australian beef. PMID: 15023647

Wheat: Would You Give Your Kids Crack?

Often the comments on Dr. Davis' HeartScanBlog are as insightful as his revolutionary ideas and core concepts. One vital core concept is wheat-cessation. From the entry 'I gained 30lbs from one cracker', Anne said... "Wheat protein contains a number of opioid peptides which can be released during digestion. Some of these are thought to affect the central and peripheral nervous systems. When I gave up gluten, I felt much worse for a few days. This is a very common reaction in those who stop eating gluten cold turkey." May 23, 2008

Fukudome S, et al. Opioid peptides derived from wheat gluten: their isolation and characterization. FEBS Lett. 1992 Jan 13;296(1):107-11. Four opioid peptides were isolated from the enzymatic digest of wheat gluten. Their structures were Gly-Tyr-Tyr-Pro-Thr, Gly-Tyr-Tyr-Pro,Tyr-Gly-Gly-Trp-Leu and Tyr-Gly-Gly-Trp, which were named gluten exorphins A5, A4, B5 and B4, respectively. The gluten exorphin A5 sequence was found at 15 sites in the primary structure of the high molecular weight glutenin and was highly specific for deltareceptors. The structure-activity relationships of gluten exorphins A were unique in that the presence of Gly at their N-termini increased their activities. Gluten exorphin B5, which corresponds to [Trp4,Leu5]enkephalin, showed the most potent activity among these peptides. Its IC50 values were 0.05 microM and 0.017 microM, respectively, on the GPI and the MVD assays. PMID: 1309704

It's hard to give up wheat for most of us on the 'spectrum'... kinda like giving up narcotics (opioids). The withdrawal won't kill you like alcohol (seizures, DTs) or benzo withdrawal (seizures), but opioid, tobacco, and caffeine cessation share similar characterics with that of wheat cessation. For one, wheat digestion releases several feel-good chemicals called opioid peptides which provide a temporary sensation of satisfaction and satiation (basically a carb dose-dependent 'high'). Studies demonstrate that wheat can actually deliver equivalent doses of morphine (see below). The wheat chemicals are extremely short-lived and their quick drop in the blood concentrations leads to cravings for more wheat/carbs that can be difficult to control.... in fact they can be downright all-consuming and overwhelming for some (even those who work out like mad creatures *heh*). Add in insulin surges and subsequent metabolic derangement and you've got a formula for an endless cycling of unsatisfying-feeding/craving. One of the most potent wheat opioid peptides B5 causes 'man-boobs' (as referenced by Kramer ala Seinfeld).
Fanciulli G, et al. Gluten exorphin B5 stimulates prolactin secretion through opioid receptors located outside the blood-brain barrier. Life Sci. 2005 Feb 25;76(15):17139. PMID: 15698850

It's enough to make you hear voices 'eat me' 'EAT ME'. Here's the link with schizophrenia, one of many neuropsych conditions which are related to toxic effects of wheat and opioid peptides. Can food make you crazy? Apparently for many humans, yes.
J Hum Nutr. 1980 Apr;34(2):107-12. Diet (gluten) and schizophrenia. Ross-Smith P, Jenner FA. Four aspects of clinical evidence for an association between gluten and schizophrenia are examined. The scientific evidence for the role of gluten is set out. Finally, reference is made to other dietary approaches. PMID: 6989901 Peptides. 1984 Nov-Dec;5(6):1139-47. Demonstration of high opioid-like activity in isolated peptides from wheat gluten hydrolysates. Huebner FR, Lieberman KW, Rubino RP, Wall JS. Because of a possible relationship between schizophrenia and celiac disease, a condition in some individuals who are sensitive to wheat gluten proteins in the diet, there has been interest in observations that peptides derived from wheat gluten proteins exhibit opioid-like activity in in vitro tests. To determine the origin of the peptides exhibiting opioid activity, wheat proteins were fractionated by size (gel filtration), by charge differences (ion exchange chromatography) and by differences in hydrophobicity (reversed-phase HPLC). These fractions were hydrolyzed by pepsin or pepsin and trypsin and the resulting peptides separated by gel filtration chromatography. The separated peptides were tested for opioid-like activity by competitive binding to opioid receptor sites in rat brain tissue in the presence of tritium-labeled dihydromorphine. The peptides showed considerable differences in activity; while some peptides exhibited no activity, 0.5 mg of the most active peptides were equivalent to 1 nM of morphine in the

binding assay. The most active peptides were derived from the gliadin fraction of the gluten complex. PMID: 6099562

Would you feed your children crack-cocaine?

(yes, I admit we do when we don't plan ahead)

'Trigger' foods we avoid because they make us fall off the proverbial band wagon... --Pepperidge farm GOLDFISH crackers --Wheat thins --Any breakfast cereal (hardly do we shop the inner aisles anymore) --Trader Joe's frozen chocolate chip cookies

Why is wheat associated with so many autoimmune conditions? The opioid peptides from wheat appear to trigger 'civil wars' and 'civil unrest' between the immune system and different organs in our bodies (including the Thyroid -- which HeartHawk is currently discussing)? Not only are wheat opioid peptides implicated in wreaking havoc on the immune system, but also in causing inordinate amounts of inflammation. And . . . inflammation leads to lymphoma (see end), cancer, and heart/vascular disease.
Manifestations of silent celiac disease (predominantly extra-intestinal): Dermatitis herpetiformis Anemia Autoimmune disorders (incl Hashimoto's, Grave's, Sjgrens, Type 1 DM, Biliary cirrhosis, Psoriasis Crohn's, Addison's) Osteoporosis Neurological disorders Epilepsy with cerebral calcification Neuropathy Cerebellar ataxia Chorea Infertility/subfertility Non-alcoholic fatty liver disease (NAFLD) Unexplained chronic hypertransaminasemia

The above list originates from the below review article (full text here). If primary focal points of celiac-related inflammation leads to lymphoma (see last citation), then can silent asymptomatic celiac disease also cause heart disease? I believe so and that is why Dr. Davis' assertion for a wheat-cessation program as critical component in the plaque regression process. Are you getting tired of the 'low-fat' mantra? It's interesting how cholesterol and fat has yet to be blamed as the cause for cancer like they have for everything else.... HHhhhmmmm..... Does cholesterol really kill us? What is causing the rise in the conditions listed above? Including autism as well (see next to the last citation)? Has the culprit always been wheat-c-a-r-b-o-h-y-d-r-a-t-e-s? These scientists Ch'ng et al note a phenomenal explosion in the presentation of celiac conditions (silent and non-silent) in the last 30yrs. Is it coincidental this mirrors changes in the pathetic SAD (standard American diet) and low-fat 'paradigm shift' to an over-reliance on wheat and whole-grains? (Is whole-grains just wholecr**p?) The celiac researchers report that most individuals with celiac disease have subtle or NO SYMPTOMS at all. In fact many test false negatively secondary to the changes in immunity (reduced IgA). Can treatment change the natural course or prevent autoimmune conditions (like Hashimoto's and Grave's disease)? Here at TYP, we strongly believe complete wheat withdrawal reverses many things. Including heart disease! These scientists summarize how research supports the improvement of many non-silent celiac disorders and the significant correction and resolution in auto-antibodies associated with Thyroid conditions.

Ventura et al 39 found that diabetes- and thyroid-related antibodies tended to disappear following a gluten-free diet (11.1% at diagnosis, 5.6% at 6 months and none at 12 or 24 months follow-up for diabetes related antibodies and 14.4%, 11.1%, 6.6% and 2.2% for thyroid related antibodies, respectively) Identifying and treating CD in high-risk patients should confer benefit in reducing complications such as malabsorption, infertility, osteoporosis and lymphoma.95,96

Ch'ng CL, Jones MK, Kingham JG. Celiac disease and autoimmune thyroid disease. Clin Med Res. 2007 Oct;5(3):184-92. Celiac disease (CD) or gluten sensitive enteropathy is relatively common in western populations with prevalence around 1%. With the recent availability of sensitive and specific serological testing, many patients who are either asymptomatic or have subtle symptoms can be shown to have CD. Patients with CD have modest increases in risks of malignancy and mortality compared to controls. The mortality among CD patients who comply poorly with a gluten-free diet is greater than in compliant patients.The pattern of presentation of CD has altered over the past three decades. Many cases are now detected in adulthood

during investigation of problems as diverse as anemia, osteoporosis, autoimmune disorders, unexplained neurological syndromes, infertility and chronic hypertransaminasemia of uncertain cause. Among autoimmune disorders, increased prevalence of CD has been found in patients with autoimmune thyroid disease, type 1 diabetes mellitus, autoimmune liver diseases and inflammatory bowel disease. Prevalence of CD was noted to be 1% to 19% in patients with type 1 diabetes mellitus, 2% to 5% in autoimmune thyroid disorders and 3% to 7% in primary biliary cirrhosis in prospective studies. Conversely, there is also an increased prevalence of immune based disorders among patients with CD.The pathogenesis of coexistent autoimmune thyroid disease and CD is not known, but these conditions share similar HLA haplotypes and are associated with the gene encoding cytotoxic T-lymphocyteassociated antigen-4. Screening high risk patients for CD, such as those with autoimmune diseases, is a reasonable strategy given the increased prevalence.Treatment of CD with a gluten-free diet should reduce the recognized complications of this disease and provide benefits in both general health and perhaps life expectancy. It also improves glycemic control in patients with type 1 diabetes mellitus and enhances the absorption of medications for associated hypothyroidism and osteoporosis. It probably does not change the natural history of associated autoimmune disorders. PMID: 18056028

Kawashti MI, Amin OR, Rowehy NG. Possible immunological disorders in autism: concomitant autoimmunity and immune tolerance. Egypt J Immunol. 2006;13(1):99-104. Autism is a pervasive developmental disorder that affect children early in their life. Immunological disorders is one of several contributing factors that have been suggested to cause autism. Thirty autistic children aged 3-6 years and thirty non-autistic psychologicallyfree siblings were studied. Circulating IgA and IgG autoantibodies to casein and gluten dietary proteins were detected by enzyme-immunoassays (EIA). Circulating IgG antibodies to measles, mumps and rubella vaccine (M.M.R) and cytomeglovirus were investigated by EIA. Results revealed high seropositivity for autoantibodies to casein and gluten: 83.3% and 50% respectively in autistic children as compared to 10% and 6.7% positivity in the control group. Surprisingly, circulating anti-measles, anti-mumps and antirubella IgG were positive in only 50%, 73.3% and 53.3% respectively as compared to 100% positivity in the control group. Anti-CMV IgG was positive in 43.3% of the autistic children as compared to 7% in the control group. It is concluded that, autoimmune response to dietary proteins and deficient immune response to measles, mumps and rubella vaccine antigens might be associated with autism, as a leading cause or a resulting event. Further research is needed to confirm these findings. PMID: 17974154

Hoggan R. Considering wheat, rye, and barley proteins as aids to carcinogens. Med Hypotheses. 1997 Sep;49(3):285-8. The increased incidence of lymphoma in celiac sprue (CS) is well documented, and the risk of developing this malignancy is 40-100-fold greater than in the general population. The author believes that gluten may also be at the root of lymphomas in asymptomatic and latent celiac sprue, as well. Among the 2030% of the population which has the HLA factors most common in celiac, increased intestinal permeability leads to absorption of macromolecular peptides with opioid activity,

which derive from pepsin digests of wheat. The presence, in the bloodstream, of these peptides may increase the risk of lymphomas for the entire hereditary group, which includes CS. Several processes contribute to the effect that is herein hypothesized, including opioid attachment at the hypothalamic-pituitary-adrenal axis (HPA), and subsequent downregulation of production of natural killer cells. This may offer an explanation for our longstanding awareness that there is an 'impaired lymphocyte reactivity against tumor cells in patients with coeliac disease' which may also apply to first-degree relatives with the same HLA markers. PMID: 9293475

Why is Vitamin A used together with Vitamin D? Why are they found in potent quantities together in nature (ie, fish liver, oily fish, salmon, oysters, trout, catfish, egg yolk, zooplankton, butter, pate, fish eggs/roe/caviar, breastmilk)? All the best foods in life... (breastmilk -- my kids were really into that stuff). Pasture-raised cows indeed produce butterfat brimming with a wealth of cardioprotective vitamins K2, A, D and E! I wonder why?? A synergistic effect has been observed for nearly all benefits studied. This makes absolute sense since they exist co-dependently physically located in the nucleus of our cells.

Synergistic cardioprotection of Vitamin D3 and retinoic acid protect against hypertrophy of neonatal rat cardiac myocytes induced by endothelin Synergistic anti-proliferative effective of vit D derivatives and 9-cis-retinoic acid on neuroblastoma cells Synergism between vit D derivative and retinoids on skeletal cells Synergistic inhibition of prostate cancer cell lines by vit D analogues and a retinoid Synergistic terminal differentiation of leukemia cells by Vitamin D3 and retinoic acid

Cardioprotective Effects of Vitamin A

(RA=retinoic acid is the carboxylic acid of vitamin A) (All-trans-retinoic acid (ATRA) is the primary active metabolite of vitamin A) (9-Cis retinoic acid, a metabolite of vitamin A, is the most potent ligand of RXR) Wu J 1996: Vitamin D3 and retinoic acid protect against hypertrophy of neonatal rat cardiac myocytes induced by endothelin Zhou MD 1995: Retinoid-dependent pathways suppress myocardial cell hypertrophy by minimizing alpha-adrenergic receptor-dependent hypertrophy Kang, Leaf 1995: All-trans-retinoic acid protects against cardiac arrhythmias induced by ischemia, adrenaline-like stimulants de Paiva 2003: Retinoic acid at small physiological doses remodeled damaged heart issue in adult rats Wang 2003: All-trans-retinoic acid prevented remodeling in cultured rat cells and cardiac hypertrophy induced by angiotensin II

Worley JR 2003: 9-cis-retinoic acid prevent MMP-9 in human monocyte-like cells de Paiva 2005: Retinoic acid supplementation attenuates ventricular modeling postmyocardial infarction in rats Preston 2005: All-trans retinoic acid elicits inhibition of serontonin-induced changes in cultured human smooth muscle cells (took cells from human subjects with idiopathic pulmonary arterial hypertension who often demonstrate low serum levels of RA and 13-cis-RA compared with healthy controls) Choudray 2007: All-trans-retinoic acid in pressure overloaded rats (by aortic band) prevented systolic and diastolic dysfunction and change in cardiac structure by inhibiting the rennin-angiotensin system. Choudray 2008: All-trans-retinoic acid prevents angiotensin II and mechanical stretch induced ROS generation cardiomyocyte cell death Mercader 2006: with retinoic acid remodeling of WAT in mice, increased thermogenesis in skeletal muscle, triggered reduction in body weight, reduction in visceral fat, improved glucose tolerance

Consider for supercharging your TYP program: Vitamin A (Natural)

Dose of Vitamin A: 5,000 to 10,000 IU** daily in the morning with food Use Natural only Side effects: Rare (unless high dose or synthetic analogue and/or vitamin D deficient -- hepatitis, hypertriglyceridemia, osteoporosis, joint aches) Food Sources: Bioavailability increases with presence of fat, fiber, protein, acidity, being heated (for vegetables; for fish, least amount of cooking maintains activity). Animal sources include liver and organ meat, red meat, whole fish, fish oils, cod liver oil, egg yolk, butter, dairy products, and breastmilk. Dark green vegetables, yellow and red fruits (excluding citrus) and vegetables, and red palm oil are rich sources of retinoids and carotenoids. Teratogenic (with high dose or synthetic analogues) -- Avoid supplementation without MD supervision if pre-conceiving, pregnant. **Caveat: Discuss with your physician prior to starting -- If you already at the TYP goal for vitamin D 25(OH)D 50 - 60 ng/ml, then consider reducing your vitamin D dose by 25-50% and re-checking the vitamin D status 25(OH)D 6-8 weeks later to verify that the 25(OH)D has not increased excessively (supratherapeutic levels). Both A and D are fat-soluble vitamins, co-factors and synergize each other's respective actions and I believe blood concentrations (like the addition of other steroid nuclear receptor agonists increases Vitamin D blood concentrations, and... vice versa. Yes...The latter has been demonstrated anecdotally. Rare studies also confirm this phenomenon). Therefore, it's prudent to reduce vitamin D supplementation if you begin vitamin A supplementation... and t-r-a-c-k i-t . :)

Astaxanthin (Natural)

Dose of Astaxanthin: 1.5 to 2 mg daily in the morning with food

Use Natural only

(Synthetic Astaxanthins are used commercially in farmed salmon, trout and other aquaculture; these fake analogues are apparently made from benzene/petrochemicals; avoid all un-natural vitamins if possible. A synthetic betacarotene, Lurotin by BASF, was shown to increase cancer, heart attacks, and mortality in clinical human trials.)

Side effects: Rare (limited human trials but so far none reported). Less joint aches, wrinkles, cancer, H.pylori dyspepsia, infections, male infertility, etc. Food sources: Microalgae, yeast, wild salmon (especially wild sockeye), wild rainbow trout, krill, shrimp, shellfish.

Cardiovascular risk modulators and telomere length reducers:

Vitamin D deficiency (25(OH)D less than 50 ng/ml) Oxidative stress Psychological stress (ie, sleep deprivation) Hypertension Estrogen deficiency Sedentary during leisure time Insulin resistance (ie, NAFLD, cardiac steatosis, metabolic syndrome, PCOS) Type 2 Diabetes Type 1 Diabetes Obesity Homocysteine Smoking (All of the above are modifieable factors in the TrackYourPlaque program)

Fuster JJ, Andrs V. Circ Res. 2006 Nov 24;99(11):1167-80. Telomere biology and cardiovascular disease. Richards JB, Valdes AM, Gardner JP, Paximadas D, Kimura M, Nessa A, Lu X, Surdulescu GL, Swaminathan R, Spector TD, Aviv A. Higher serum vitamin D concentrations are associated with longer leukocyte telomere length in women. Am J Clin Nutr. 2007 Nov;86(5):1420-5. Aviv A. Hypothesis: pulse pressure and human longevity. Hypertension. 2001 Apr;37(4):1060-6. W. Browner, et al. The genetics of human longevity. The American Journal of Medicine, Volume 117, Issue 11, Pages 851-860. Kenyon C. The plasticity of aging: insights from long-lived mutants. Cell. 2005 Feb 25;120(4):449-60. Njajou OT, Cawthon RM, Damcott CM, Wu SH, Ott S, Garant MJ, Blackburn EH, Mitchell BD, Shuldiner AR, Hsueh WC. Telomere length is paternally inherited and is associated with parental lifespan. Proc Natl Acad Sci U S A. 2007 Jul 17;104(29):12135-9. Haussmann MF, Mauck RA. Telomeres and longevity: testing an evolutionary hypothesis. Mol Biol Evol. 2008 Jan;25(1):220-8. Richards JB, et al. Homocysteine levels and leukocyte telomere length. Atherosclerosis. 2008 Feb 14; [Epub ahead of print] Cherkas LF, et al. The association between physical activity in leisure time and leukocyte telomere length. Arch Intern Med. 2008 Jan 28;168(2):154-8.

Control Insulin (Part Two)

Briefly, the history of insulin and its relationship to atherosclerosis: Stout RW. Insulin and atheroma. 20-yr perspective. Diabetes Care. 1990 Jun;13(6):631-54. Review. PMID: 2192848 Department of Geriatric Medicine, Queen's University of Belfast, Northern Ireland.
Many clinical studies have shown an increased insulin response to oral glucose in patients with ischemia of the heart, lower limbs, or brain. Hyperinsulinemia also occurs in patients with angiographically proved atherosclerosis without ischemia and thus appears to be related to arterial disease and not to be a nonspecific response to tissue injury. Fasting insulin levels and insulin responses to intravenous stimuli, including glucose, tolbutamide, and arginine, are normal, suggesting a gastrointestinal factor may be involved in the increased insulin response to oral glucose. In patients with atherosclerosis, insulin sensitivity appears to be normal or enhanced with respect to both glucose and lipid metabolism. Five population studies have shown that insulin responses to glucose are higher in populations at greater risk of cardiovascular disease. Many of the hyperinsulinemic populations also had upper-body obesity, hypertriglyceridemia, lower high-density lipoprotein (HDL) levels, and hypertension. These prospective studies support an independent association between hyperinsulinemia and ischemic heart disease, although their results differ in detail. Hyperinsulinemia is associated with raised triglyceride and decreased HDL cholesterol levels. Total and low-density lipoprotein (LDL) cholesterol is less closely related to hyperinsulinemia. Upper-body adiposity is associated (in separate studies) with coronary heart disease, diabetes, hyperinsulinemia, and hypertriglyceridemia. Insulin and blood pressure are closely related in both normotensive and hypertensive people. Although obesity and diabetes are often found in hypertensive people, hyperinsulinemia also occurs in nonobese nondiabetic hypertensive people. Thus, hyperinsulinemia is closely associated with a cluster of cardiovascular risk factors, i.e., hypertriglyceridemia, low HDL levels, hypertension, hyperglycemia, and upper-body obesity. There is a possibility that insulin has a role in the sex differences in ischemic heart disease incidence and their absence in diabetes, but additional work is required for its clarification. Long-term treatment with insulin results in lipid-containing lesions and thickening of the arterial wall in experimental animals. Insulin also inhibits regression of diet-induced experimental atherosclerosis, and insulin deficiency inhibits the development of arterial lesions. Insulin stimulates lipid synthesis in arterial tissue; the effect of insulin is influenced by hemodynamic factors and may be localized to certain parts of the artery. In physiological concentrations, insulin stimulates proliferation and migration of cultured arterial smooth muscle cells but has no effort on endothelial cells cultured from large vessels. Insulin also stimulates cholesterol synthesis and LDL binding in both arterial smooth muscle cells and monocyte macrophages.

Despres JP et al showed in the below study how elevated fasting insulin blood levels was closely associated to the presence of ischemic heart disease. The higher the concentration of insulin, the greater the odds ratio. And additionally they found other factors compounded the risk of heart disease:

--High Triglyercides --High Total/HDL ratio (in other words, low HDL) --High Apolipoprotein B

Desprs JP, Lamarche B, Maurige P, Cantin B, Dagenais GR, Moorjani S, Lupien PJ.Hyperinsulinemia as an independent risk factor for ischemic heart disease.N Engl J Med. 1996 Apr 11;334(15):952-7. PMID: 8596596

Figure. Odds Ratios for Ischemic Heart Disease according to Plasma Insulin and Triglyeride Concentrations, Total:HDL Cholesterol Ratios, and Apolipoprotein B Concentrations. Insulin was measured after subjects had fasted for 12 hours. The median TG concentration (150 mg/dl [1.7mmol/L]), total:HDL ratio (6.0), and apoplipoprotein B concentration (119 mg/dl) were used to define men with either low levels (below the 50th percentile) or high levels (at or above the 50th percentile) for these variables. The results of tests of multiplicative interactions did not reach signficance at the 0.05 level for any of the combinations. P values are for comparisons with the reference group, which was assigned an addos ratio of 1.0. To convert values for insulin to picomoles per liter, multiply by 6.

The researchers Lemarche et al have done a great deal of research examining 'nontraditional risk factors '(see Table 2) and also showed the same link between insulin

and associated ischemic heart disease.

Lamarche B, Tchernof A, Maurige P, Cantin B, Dagenais GR, Lupien PJ, Desprs JP. Fasting insulin and apolipoprotein B levels and low-density lipoprotein particle size as risk factors for ischemic heart disease. JAMA. 1998 Jun 24;279(24):1955-61. (Full PDF here) PMID: 9643858

In fact, their results uncovered the fact that the largest odds ratio between traditional (LDL, TG, HDL) and nontraditional (small dense LDL, apo B and fasting insulin) fell to the Hyperinsulinemia risk factor. So high fasting insulin correlated stronger with the presence of evidence of coronary artery disease than than LDLcholesterol. Triglyericides (TGs) even associated to a higher degree than LDLcholesterol. HHmmmm? Why do we always call LDL the 'bad' cholesterol? It appears that TGs is a bad character, indeed it appears TGs are the worse cholesterol out of all the traditional risk factors! Dr. Davis has pursued a lower TG goal lower than 'traditional' guidelines for many years. Current 'conventional' cardiovascular advice aims for TGs less than 150 however the Track Your Plaque program advocates an aggressive TG goal of 'normal' less than 60. Is the 'LDL-cholesterol hypothesis' completely bunk? Shouldn't Triglyerides be known as the 'lousy/bad' cholesterol? Is this why statin-monotherapy fail to prevent signficant mortality and morbidity

caused by plaque in heart disease and strokes? The TYP goals for regression of ischemic heart disease are 60-60-60-60 (TG-HDLLDL-25(OH)D). Many achieve this and beyond -- HDLs 80-90s and TGs 25-50s in the program! And Elevated Fasting Insulin goal is not just less than 12 mU/L as discussed in the 2nd study above but at TYP the goal for regression is normal fasting insulin levels less than 5-10 mU/mL (30-60 pmol/L). Is this why the Track Your Plaque program controls plaque comprehensively and trumps all 'conventional' cardiology programs by controlling triglycerides and insulin by a multifaceted strategy? --Vitamin D3 --Wheat and grain cessation --Exercise --Weight loss to achieve normal BMI --High/ultra-high dose fish oil EPA+DHA --Hormone optimization (estrogen, testosterone, DHEA, etc) --Vitamins K2/E/A --Et cetera Conclusions by the above authors Lamarche, et al:
'Beyond the mechanisms underlying the atherogenicity of hyperinsulinemia, hyperapobetalipoproteinemia, and small, dense LDL, and irrespective of whether these mechanisms share common paths, results of the present study suggest that the risk of IHD is increased substantially when these metabolic abnormalities cluster. The synergistic contribution of the nontraditional cluster of risk factors to IHD risk and the fact that almost 1 of every 2 IHD cases had these abnormalities simultaneously reflect the multifactorial etiology of IHD. It also emphasizes the importance of defining the risk of IHD based on more than 1 risk factor. There are a number of critical issues that have to be considered before any decision can be made toward the measurement of these nontraditional risk factors on a routine basis. Among others, results of this prospective case-control study will have to be confirmed through larger population-based studies, as the relatively low number of IHD cases allowed only a gross assessment of risk. The relatively large CIs associated with the estimated risk in some of the subgroups reflect this phenomenon. Population reference values such as those used for LDL-C, triglycerides, and HDL-C also will be needed before critical levels of fasting insulin, apolipoprotein B levels, and LDL particle size or density at which a person becomes

at greater risk for IHD are identified. Means to achieve effective treatment of the nontraditional risk factors is also a critical issue that deserves a great deal of scrutiny before decisions can be made toward use of these variables in the risk management of IHD. There are data to suggest that LDL particle size can be modulated by changes in plasma triglyceride levels.41 Studies have shown that triglyceride-lowering therapy with fibric acid derivatives can lead to a significant increase in LDL particle size.42-43 There is also a large body of evidence demonstrating that LDL particle size, apolipoprotein B level, and insulin resistance and/or hyperinsulinemia can be effectively altered by diet and exercise-induced weight loss.44-45 Thus, the ability to favorably modify the nontraditional risk factors by diet, exercise, and appropriate pharmacotherapy provides further support for the use of these risk factors in the management of IHD risk...'

Lawlor DA, Fraser A, Ebrahim S, Smith GD. Independent associations of fasting insulin, glucose, and glycated haemoglobin with stroke and coronary heart disease in older women. PLoS Med. 2007 Aug;4(8):e263. PMID: 17760500 Full PDF here: Editor's Summary
Background: Narrowing of the vessels that take blood to the heart and brain is a common form of cardiovascular diseasei.e., a disorder of the heart and blood vessels. It is a major cause of illness and death. By starving the heart and brain of oxygen, this condition causes coronary heart disease (CHD; heart problems such as angina and heart attacks) and strokes. A major risk factor for CHD and strokes is diabetes, a common chronic disease characterized by high levels of sugar (glucose) in the blood. In people who don't have diabetes, the hormone insulin controls blood-sugar levels. Insulin, which is released by the pancreas after eating, instructs insulin-responsive muscle and fat cells to absorb the glucose (released from food) from the bloodstream. In the very early stages of type 2 diabetes (the commonest type of diabetes, also called adult onset or noninsulin-dependent diabetes), muscle and fat cells become unresponsive to insulin, so blood-sugar levels increase. This is called insulin resistance. The pancreas responds by making more insulin. As a result, people with insulin resistance have high blood levels of both insulin (hyperinsulinemia) and glucose (hyperglycemia). Eventually, the insulin-producing cells in the pancreas start to malfunction, insulin secretion decreases, and type 2 diabetes is the result.

Conclusions:
'Our findings indicate that amongst older women without diabetes and with fasting glucose levels in the normal range, fasting insulin is a stronger predictor of CHD and stroke risk than are fasting glucose or HbA1c.' In addition, the results demonstrated a 'positive linear association between fasting insulin and CHD and stroke events is consistent with findings from the Atherosclerosis Risk in

Communities study (SEE LAST CITATION), in which there was a positive linear association with CHD events that remained after adjustment for other CHD risk factors amongst women, but not amongst men [27]. A metaregression analysis of 17 prospective studies, primarily conducted in men and younger age groups than the current study, found a pooled relative risk of CHD per 50 pmol/l of insulin of 1.18 (95% CI 1.081.29) [9], which is consistent with our fully adjusted association with CHD (our results equate to 1.13 [95% CI 1.011.27] per 50 pmol/l of insulin). Overall the evidence suggests a modest positive association between fasting insulin and CHD events in women and men. Fasting insulin may exert its effect on cardiovascular risk via a direct impact on endothelial function [28,29].'

CRACK DOWN on insulin... CRACK DOWN on plaque (and cancer)... Hunger will disappear away as well. Part of insulin's purpose is to drive energy into cells for storage. Insulin drives hunger as well. (...and mainly the consumption of carbs drive insulin secretion) You will realize the benefits of low blood insulin and will often 'forget' to eat without prompting from this powerful hormone. You'll hunger for other things... vitality, movement, effortless-boundless ENERGY.

Importance of controlling triglycerides and insulin: INSULIN ==> TG/HDL ratio ==> SMALL DENSE LDL Zavaroni I, Dall'Aglio E, Alpi O, Bruschi F, Bonora E, Pezzarossa A, Butturini U. Evidence for an independent relationship between plasma insulin and concentration of high density lipoprotein cholesterol and triglyceride. Atherosclerosis. 1985 Jun;55(3):259-66. PMID: 3893447 [PubMed - indexed for MEDLINE] Ghiselli G, Bon GB, Soldan S, Avogaro P. Regulatory function of glucose and insulin on high-density lipoprotein cholesterol in normolipidemic subjects. Metabolism. 1994 Nov;43(11):1332-7. PMID: 7968586 [PubMed - indexed for MEDLINE] Cominacini L, Garbin U, Davoli A, Campagnola M, De Santis A, Pasini C, Pastorino AM, Bosello O. High-density lipoprotein cholesterol concentrations and postheparin hepatic and lipoprotein lipases in obesity: relationships with plasma insulin levels. Ann Nutr Metab. 1993;37(4):175-84.

PMID: 8215234 [PubMed - indexed for MEDLINE] Laws A, King AC, Haskell WL, Reaven GM. Relation of fasting plasma insulin concentration to high density lipoprotein cholesterol and triglyceride concentrations in men. Arterioscler Thromb. 1991 Nov-Dec;11(6):1636-42. PMID: 1931867 [PubMed - indexed for MEDLINE] Stalder M, Pometta D, Suenram A. Relationship between plasma insulin levels and high density lipoprotein cholesterol levels in healthy men. Diabetologia. 1981 Dec;21(6):544-8. PMID: 7040144 [PubMed - indexed for MEDLINE] Tchernof A, Lamarche B, Prud'Homme D, Nadeau A, Moorjani S, Labrie F, Lupien PJ, Desprs JP. The dense LDL phenotype. Association with plasma lipoprotein levels, visceral obesity, and hyperinsulinemia in men. Diabetes Care. 1996 Jun;19(6):629-37. PMID: 8725863 [PubMed - indexed for MEDLINE] Laws A, Reaven GM. Evidence for an independent relationship between insulin resistance and fasting plasma HDL-cholesterol, triglyceride and insulin concentrations. J Intern Med. 1992 Jan;231(1):25-30. PMID: 1732395 Katzel LI, Coon PJ, Rogus E, Krauss RM, Goldberg AP. Persistence of low HDL-C levels after weight reduction in older men with small LDL particles. Arterioscler Thromb Vasc Biol. 1995 Mar;15(3):299-305. PMID: 7749838 McNamara JR, Jenner JL, Li Z, Wilson PW, Schaefer EJ. *** Change in LDL particle size is associated with change in plasma triglyceride concentration. Arterioscler Thromb. 1992 Nov;12(11):1284-90. PMID: 1420088 Folsom AR, Szklo M, Stevens J, Liao F, Smith R, Eckfeldt JH. ** A prospective study of coronary heart disease in relation to fasting insulin, glucose, and diabetes. The Atherosclerosis Risk in Communities (ARIC) Study. Diabetes Care. 1997 Jun;20(6):935-42. PMID: 9167103

Control Insulin, Control Plaque... (And Cancer)

Controlling insulin reaps many rewards. As the previous article suggests, insulin is an ancient hormone ubiquitous in all animals -- from worms to humans -- with classic/nonclassic responsibilities including (see Table 1). Some of these actions are beneficial like Thermogenesis, however many of the others are detrimental in the great majority of situations: --low potassium --raised heart rate --increased uric acid (ie, gout) --increased clotting --CNS stimulation (ie, anxiety, epression, ADHD) --prevention of fat from being liberalized for energetic uses We require only tiny, neglible amounts of insulin for thermogenesis and shuttling of energy (glucose) into muscles and liver for storage. In fact, increased energy expenditure is exponentially increased when insulin resistance is kept at bay. What is insulin resistance (IR)? It is like being at a rock concert (or Hannah Montana venue with screaming little girls everywhere) where temporary hearing loss is induced by inclement noise pollution. As soon as the volume returns to a low level, hearing resumes. Shut insulin down by going grainfree, carb-restricted, intermittent fasting and exercising, then inflammatory responses and processes are cut off. The same research demonstrated that men and women have blunted energy expenditure when the 'volume of insulin' is dialed exceptionally high. And for us women, we may even have a 'negative' energy output (in other words 'storage') with energy expenditure during the presence of insulin resistance... huhhh??! Talk about an exceedingly 'thrifty' gene... *urgh* Insulin-resistant gals gain weight with exercise... how exceedingly unfair. This actually is a common phenomenon and very discouraging for women trying to lose weight and fight an uphill battle as they eat per conventional medical advice 'low fat'/high-carbohydrate/insulin-inducing diets (USDA 'whole grain' pyramidal nonsense).

Degrees of IR can also be effectively cranked down by (Isharwal S, et al. Dietary nutrients and insulin resistance in urban Asian Indian adolescents and young adults.Ann Nutr Metab. 2008;52(2):145-51.): --normal BMI achievement --reduction of pro-inflammatory omega-6 oils --increase of anti-inflammatory omega-3 EPA+DHA oils (ie, cod liver, fish oil, pasture-fed milk, meat, eggs, etc) And of course...wheat avoidance, grain elimination, carb restriction, intermittent fasting and exercise. Excessive insulin (ie, hyperinsulinemia) leads to the below changes (see below diagram): --inflammation --generation of TGs and small dense atherogenic LDL --conversion from fatty streaks to plaque --plaque growth --increased adipose tissue mass (Obesity, Metablic Syndrome, PCOS) --accumulation of Triglycerides in non-adipocytes --nonalcoholic steatohepatitis (fatty liver/NAFLD) --pancreatic beta-cell failure (fatty pancreas, insulin resistance) --dilated cardiomyopathy (myocyte (heart cell) stiffening and diastolic dysfunction) --arterial stiffening --blood glucose spikes --expansion of visceral fat (belly fat colonies) --fatty liver, fatty pancreas, fatty gallbladder, fatty heart --Diabetes Type 2 --strokes, heart attacks --cancer (see end)

So... when insulin becomes rampant and uncontrolled like ex-KGB-satellites gaining prominence and power to control global McMafia-like franchises for cocaine, opioid, and crack trafficking, then world and global economies are undoubtedly affected. Whole human systemic organ functions become dominated by hyperinsulinemia, leading to all sorts of dysfunction and energy dysregulation. Why rely on primitive petrol... when nuclear power exists?

Fig 1. Lipotoxicity in humans originates from excessive release of free fatty acids from hypertrophied adipocytes in obese persons. Organ exposure to high levels of free fatty acids causes lipid droplets to accumulate within the cytosol of nonadipose tissues in proximity to mitochondria (white arrows, bottom).By-products of cytosolic triglyceride accumulation and of lipid metabolism may lead to organ dysfunction and failure. McGavock JM, Victor RG, Unger RH, Szczepaniak LS. Adiposity of the heart, revisited. (Full PDF here.) Ann Intern Med. 2006 Apr 4;144(7):517-24. Review. PMID: 16585666

The inflammation associated with insulin is akin to the oxidative damage that occurs when soft materials like rubber or plastic is left outside exposed to the elements. Over time, the rubber hardens and becomes inelastic and rigid, easily breaking with any shear force. Sort of like running a high-powered hose made out of glass, right? With the elimination of inflammatory influences, human tissues can return to their original soft, elastic, pliable states. This includes endothelium, heart blood vessels, contractile tissues like our heart and skeletal muscles... even our oral gum tissues! Reversal occurs when insulin is shut down.

The previous review of the research eloquently illustrates the special properties that dictate this ancient 'reactive' hormone. Insulin is one of the few hormones that is controlled by consumed 'substrates'.... What is in charge of turning insulin on and off? What are substrates of insulin? C-A-R-B-O-H-Y-D-R-A-T-E-S. Found in our daily meals and snacks! What we consume indeed dictates what we are (biochemically speaking). Food composition directly lowers or raises insulin concentrations. Various other factors of course determine how quick and how sustained hyperinsulinemia occurs (exercise, weight loss, skeletal muscle dominance, size and location of visceral fat colonies (ie, 'belly' is 'bad') but in essence our food controls blood insulin levels. If what we put in our mouth dictates are insulin levels, then equally powerful is what we don't... In other words, processes like starvation, skipping meals, random eating, intermittent fasting and going low-carb or restricted-carb are ways to reduce and control insulin. Consumption of adequate protein and fats and fiber control insulin release as well. Take powerful control over plaque and inflammatory processes by shutting insulin secretion off. At Track Your Plaque the Paleo grain-free diet produces the best plaque-busting results. Consider the complete avoidance of all wheat and grains: --wheat --wheat products (incl cereal, pasta, noodles, bread, crackers, pita, tortilla) --buckwheat --bulgur (cracked wheat) --barley --rye --oat (except oat bran) --quinoa --rice --corn (incl popcorn, grits, cornmeal, tortilla, chips) --couscous

--amaranth --millet --sorghum --triticale --et cetera Consume most of the carbohydrates from non-starchy vegetables and raw nuts/seeds and low-GI fruit like berries. Controlling insulin not only controls CAD but also controls cancer... Is 'whole grains' just promoting 'whole C-A-N-C-E-R'? As well as 'whole CORONARY ARTERY DISEASE'? --breast cancer --prostate cancer --colon cancer --pancreatic cancer

Berstein LM. Endocrinology of the wild and mutant BRCA1 gene and types of hormonal carcinogenesis. Future Oncol. 2008 Feb;4(1):23-39. Review. PMID: 18240998 Hede K.Doctors seek to prevent breast cancer recurrence by lowering insulin levels. J Natl Cancer Inst. 2008 Apr 16;100(8):530-2. PMID: 18398091 Barnard RJ.Prostate cancer prevention by nutritional means to alleviate metabolic syndrome. Am J Clin Nutr. 2007 Sep;86(3):s889-93. Review.PMID: 18265484 Park JH.Inhibition of colon cancer cell growth by dietary components: role of the insulinlike growth factor (IGF) system. Asia Pac J Clin Nutr. 2008;17 Suppl 1:257-60. PMID: 18296350 Tenenbaum A, et al. Does the lipid-lowering peroxisome proliferator-activated receptors ligand bezafibrate prevent colon cancer in patients with coronary artery disease? Cardiovasc Diabetol. 2008 Jun 19;7(1):18. PMID: 18565233 Pisani P. Arch Physiol Biochem. 2008 Feb;114(1):63-70. Hyper-insulinaemia and cancer, meta-analyses of epidemiological studies. Background: A substantial body of evidence links sex hormones, diet, excess body weight and physical activity to the risk of developing cancer at several sites common in affluent countries. The hypothesis that high circulating levels of insulin could be the underlying factor increasing cancer risk has been proposed. Epidemiological studies on markers of hyper-insulinaemia and cancer are reviewed and summarized. Methods: Studies of cancers of the colon and rectum, pancreas, breast, and endometrium examining the association with blood levels of C-peptide, insulin, glucose, glycated haemoblobin (HbA1c) were searched in PubMed. Multivariate, adjusted relative risks (RR) and their 95% confidence intervals were abstracted and summarized by meta-analyses. Results: Most of the studies identified were cohorts that relied on measurements obtained at baseline or assessed in blood stored at low temperature several years before the onset of cancer. The meta-analyses showed excess risks of colorectal and pancreatic cancers associated with higher levels of circulating C-peptide/insulin and with markers of glycaemia. Significant heterogeneity was found among four epidemiological studies of

endometrial cancer and C-peptide giving a summary RR compatible with no association. Overall breast cancer risk was significantly higher in the upper categories of Cpeptide/insulin, however, the excess derived entirely from retrospective studies. Conclusion: Current evidence suggests that subjects who develop colorectal and pancreatic cancers have increased pre-diagnostic blood levels of insulin and glucose. PMID: 18465360

Ancient Insulin... Modern Metabolic Chaos and Cancer

When the Russian empire fell, civil, political, financial chaos ensued. A new book titled McMafia recently came out. The author Misha Glenny recently appeared on Charlie Rose to discuss what his investigative reporting illuminated over the last few years. He made interesting comments about how the ex-KGB were suddenly in essence 'forced' to command new 'mafia-like' outposts after the regime was reordered (or dysregulated). Naturally, the public could not rely on the state for policing. Who was more sophisticated and trained? Real mafia or the governmentsponsored with access to the latest research, gadgets, military surveillance and satellite technology? Actually, that may be a difficult one to answer... Naturally, a new order was created and in fact so well the author reports that they now run dominant global operations (demonstrating strong entrepreneurial spirit! and franchise facets!). Similar derangement (and 'reconfiguration' of diseased organs) occurs when carbohydrates are introduced to human metabolism...Chaos, inflammation, blood thickening, increased heart rate, lower TSH, higher cortisol (more neuropsych issues; sodium retained), high uric acid (UA;gout), high blood pressure, decreased vagal tone (more anxiety), vascular tone goes down the drain (leading to plaque an arterial stiffness). Cancer...? Coronary artery disease...? Even mental derangement (like PMS, ADHD, depression)? Kinda like putting water in your gas tank... Need a little humidity and moisture for petrol/gasoline to flow, however if excessive water mixes in, the engine and carburetor will eventually be ruined.

Approximately ten years ago, Ferrannini et al wrote a revised canon for insulin actions entitled 'Insulin: New Roles for an Ancient Hormone.' Insulin not only has several responsibilities including the process of transporting energy (glucose) into muscles and the liver, but also has many other actions when excessive and over-represented and un-directed. Insulin is an ancient peptide hormone and evolutionarily tightly conserved -- expressed in tissues of all species vertebrate and non-vertebrate... including C.elegans the longevity worm-model. What is the downstream effect of insulin on worms? Shortened lifespan. The funny thing about this peptide hormone is that there is no direct central controller. It is like a de-centralized satellite KGB agent. No pituitary or hypothalamic hormone flips insulin 'on' or 'off'. The authors wrote insulin's 'release is driven by its substrate, with no apparent central integration.'

Insulin: new roles for an ancient hormone. Ferrannini E, et al. Eur J Clin Invest. 1999 Oct;29(10):842-52. Recent research has greatly expanded the domain of insulin action. The classical action of insulin is the control of glucose metabolism through the dual feedback loop linking plasma insulin with plasma glucose concentrations. This canon has been revised to incorporate the impact of insulin resistance or insulin deficiency, both of which alter glucose homeostasis through maladaptive responses (namely, chronic hyperinsulinaemia and glucose toxicity). A large body of knowledge is available on the physiology, cellular biology and molecular genetics of insulin action on glucose production and uptake. More recently, a number of newer actions of insulin have been delineated from in vitro and in vivo studies. In sensitive individuals, insulin inhibits lipolysis and platelet aggregation. In the presence of insulin resistance, dyslipidaemia (HIGH TGs, LOW HDLs, HIGH apoB, HIGH Lp(a)), hyper-aggregation and anti-fibrinolysis may create a prothrombotic milieu. Preliminary evidence indicates that hyperinsulinaemia per se may be pro-

oxidant both in vitro and in vivo. Insulin plays a role in mediating diet-induced thermogenesis, and insulin resistance may therefore be implicated in the defective thermogenesis of diabetes. In the kidney, insulin spares sodium and uric acid from excretion; in chronic hyperinsulinaemic states, these effects may contribute to high blood pressure and hyperuricaemia. Insulin hyperpolarises the plasma membranes of both excitable and non-excitable tissues, with consequences ranging from baroreceptor desensitisation to cardiac refractoriness (prolongation of QT interval). Under some circumstances insulin is vasodilatory-the mechanism involving both the sodium-potassium pump and intracellular calcium transients. Finally, by crossing the bloodbrain barrier insulin exerts a host a central effects (sympatho-excitation, vagal withdrawal, stimulation of corticotropin releasing factor), collectively resembling a stress reaction. Description and understanding of these new roles, their interactions, the interplay between insulin resistance and hyperinsulinaemia, and their implications for cardiovascular disease have only begun. PMID: 10583426

The insulin receptor: a new ANTI-CANCER target for peroxisome proliferator-activated receptor-gamma (PPARgamma) and thiazolidinedione-PPARgamma agonists. Costa V, et al. Endocr Relat Cancer. 2008 Mar;15(1):325-35. The peroxisome proliferator-activated receptor-gamma (PPARgamma) is a member of the nuclear hormone receptor superfamily. Ligand activation of PPARgamma is associated with differentiation and inhibition of proliferation in the normal and malignant cells. Herein, we studied the effects of PPARgamma and the PPARgamma agonists thiazolidinediones (TZDs) on the insulin receptor (IR), a cell membrane tyrosine kinase receptor protein, whose role is of paramount importance in mediating the metabolic and growth-promoting effects of the peptide hormone insulin. Overexpression of the PPARgamma1 in human hepatocellular (HepG2) cells was associated with decreased IR gene transcription and protein expression levels, and these reductions were more evident in the presence of TZDs. Since no PPARgamma response elements were identified on the IR promoter, we postulated that PPARgamma adversely affects the IR gene transcription by perturbing the assembly and stability of the transcriptionally active multiprotein-DNA complex identified previously, which includes the high-mobility group A1 protein, the ubiquitously expressed transcription factor (Sp1), the CAAT enhancer-binding protein (C/EBPbeta), and, in some cell lines, the developmentally regulated activator protein-2 (AP-2) transcription factor. Using glutathione S-transferase pull-down assays combined with electrophoretic mobility shift assay and chromatin immunoprecipitation, we demonstrated that by interacting with Sp1, C/EBPbeta, and AP-2, PPARgamma can prevent Sp1/AP-2 proteinprotein association and inhibit binding of Sp1 and C/EBPbeta to DNA, thus reducing IR gene transcription. Our results demonstrate that IR is a new target gene of PPARgamma, and support a potential use of TZDs as anti-proliferative agents in selected neoplastic tissues overexpressing IRs. PMID: 18310298

Wheat: Raises Insulin and Upregulates 'Bad' Genes

Can our food alter gene expression? Absolutely so! As Hippocrates once said, 'Let food by thy Medicine... and Medicine thy Food.' I'm sure he didn't mean medications as they exist now as chemicals or benzene rings (derived from petroleum) mass synthesized in factories for global consumption. The below FUNGENUT study recently showed the importance of how different sources of carbohydrate containing foods immediately changes gene expression in our favorite organ -- the omentum -- the stubborn fat lying on our bellies -- yes, the one covering up your those fabulous 6-pack abs. (Diagram: Ludwig, D. (2002) JAMA )

In a small group of subjects, 2 diets (Rye-Pasta -- mildly lower in GI; Oat-WheatPotato -- high GI carbs) were compared for 3 months. At the end no change in weight or insulin resistance, insulin levels, or glucose concentrations occurred. The profile for insulin (1st phase) secretion mildly improved in the Rye-Pasta group. Interestingly, other than showing that wheat sucks (and perhaps oat and potato) gene expression was entirely affected by simple changes in carbohydrate content and the Glycemic Index (GI measures how long and how fast glucose enters the blood stream after consumption). Rye (endosperm) bread has a GI (glycemic index) of approximately 60-70. Pasta's GI is about 60-70 as well (depending on the type and how al dente/not-overcooked).

Wheat bread on the other hand is about 90-100 (close to pure glucose). Oats about 70 and potatoes 80-100 (without cream or butter which slows the uptake of starches into the stomach blood circulation which would effectively lower the GI). American Russet potato even exceeds glucose, 110 (!wow).

CARBOHYDRATE COMPOSITION OF FOOD PROVIDE MOLECULAR EFFECTS AND LOWGI CARBS DOWNREGULATE 'BAD' GENES: "Prior microarray studies found differences in gene expression between overweight and lean individuals (2) and after energy restriction (3); however, changes in the ratio of fat to carbohydrate did not alter gene expression (3). The study by Kallio et al makes a significant contribution to the literature by demonstrating the potentially major effects of dietary composition on gene regulation, independent of energy intake and body weight. Two specific findings concerning the low-insulin-response diet merit particular attention: the down-regulation of both hormone-sensitive lipase (HSL) and TCF7L2. " "HSL, a key enzyme in the release of fatty acids from adipose tissue, has been proposed to affect body weight and metabolic variables. Mice made deficient in HSL by genetic manipulation are resistant to genetic- or diet-induced obesity (4, 5). Women carrying an allele associated with decreased HSL activity have lower fasting and simulated insulin concentrations, and men with this allele have lower nonesterified fatty acid concentrations (6)..." "The transcription factor TCF7L2 is the strongest known genetic predictor of type 2 diabetes. A microsatellite within intron 3 of this transcription factor occurs with increased frequency in individuals with type 2 diabetes, which corresponds to an estimated population attributable risk of 21% (7)..." "The present study (BELOW) has direct implications concerning our understanding of the dietary glycemic index (GI). The GI is a system for classifying carbohydratecontaining foods according to how blood glucose concentrations change in the postprandial period (reviewed in reference 8). High-GI meals produce greater postprandial insulin concentrations and C-peptide excretion than do nutrientcontrolled low-GI meals. Observational and interventional studies have linked GI to the risk of obesity, diabetes, heart disease, and cancer, although the topic remains much debated. One factor contributing to this ongoing controversy is the relative paucity of data regarding the relevant molecular mechanisms. If differences in insulin secretion mediate the genetic effects observed by Kallio et al, similar effects would be expected to occur with both low-GI and high-GI diets. This possibility is supported by a human study and several rodent studies, which showed potentially

beneficial changes in the expression of HSL and other relevant genes with a low-GI diet (8, 9)." Contrastingly, the high-GI wheat (+oat+potato) diet upregulated 62 genes including those associated with: -- Stress -- Oxidative damage -- Impaired immunity So... high carb diet translates to... the equivalence of a STRESS RESPONSE. The authors discuss in more depth the results from the FUNGENUT Study..."Interestingly, the 12-wk oat-wheat-potato diet seemed to especially activate genes responding to stress. The oxidative stress pathway, interleukin pathway, and inflammation mediated by the chemokine and cytokine signaling pathway were also activated. Moreover, the present data suggest that the oatwheat-potato diet, which induced repeated high insulin responses, can provoke alterations in immune status and inflammation. It is well established that adipose tissue has a role in inflammation (39). Cross-sectional epidemiologic data suggest that whole grains and a low-glycemic-index diet may reduce systemic inflammation in women with T2DM (40). Up-regulation of gene expression for serum and glucocorticoid-regulated kinase suggests activation of the glucocorticoid axis, which can occur in response to various stress stimuli (cytokines, aldosterone, growth factors, oxidative stress, heat shock protein activation, and glucocorticoids) (41). Activation of the pituitary-adrenal glucocorticoid axis may be involved in the pathogenesis of the metabolic syndrome (42)."
Dietary carbohydrate modification induces alterations in gene expression in abdominal subcutaneous adipose tissue in persons with the metabolic syndrome: the FUNGENUT Study. Kallio P, et al. Am J Clin Nutr. 2007 May;85(5):1169-70. Department of Clinical Nutrition, Food and Health Research Centre, University of Kuopio, Kuopio, Finland. BACKGROUND: Diets rich in whole-grain cereals and foods with a low glycemic index may protect against type 2 diabetes, but the underlying molecular mechanisms are unknown. OBJECTIVE: The main objective was to test whether 2 different carbohydrate modifications-a rye-pasta diet characterized by a low postprandial insulin response and an oat-wheatpotato diet characterized by a high postprandial insulin response--affect gene expression in subcutaneous adipose tissue (SAT) in persons with the metabolic syndrome. DESIGN: We assessed the effect of carbohydrate modification on SAT gene expression in 47 subjects [24 men and 23 women with a mean (+/-SD) age of 55 +/- 6 y] with the features of the metabolic syndrome in a parallel study design. The subjects had a mean (+/-SD) body mass index (kg/m(2)) of 32.1 +/- 3.8 and a 2-h plasma glucose concentration of 8.0 +/- 2.3 mmol/L. Adipose tissue biopsies were performed, and oral-glucose-tolerance tests and other biochemical measurements were conducted before and after the intervention. RESULTS: We detected 71 down-regulated genes in the rye-pasta group, including genes linked to insulin signaling and apoptosis. In contrast, the 12-wk oat-wheat-

potato diet up-regulated 62 genes related to stress, cytokine-chemokinemediated immunity, and the interleukin pathway. The insulinogenic index improved after the rye-pasta diet (P=0.004) but not after the oat-wheat-potato diet. Body weight was unchanged in both groups. CONCLUSIONS: Dietary carbohydrate modification with rye and pasta or oat, wheat, and potato differentially modulates the gene expression profile in abdominal subcutaneous adipose tissue, even in the absence of weight loss. PMID: 17490981

These wonderful graphs from Finland researchers illustrate how the toxic effects of grain sources of carbohydrates occur when wheat and rye are fed to healthy volunteers. Above a glucose blood concentration of 150 mg/dl (=8.3 mmol/L), glucose starts to cause changes in protein folding and glycosylating proteins and tissues. Diabetes micro-vascular complications like eye/kidney/nerve ending damage are related to toxic concentrations of glucose. Imagine sugar coating the organs over time. The higher the concentration, the longer the duration, the more thicker and more damaging the sugar coating. Insulin is controlled by several factors. Food is one of the most potent controllers, with carbohydrates and their respective GIs raising insulin levels the most. Excessive insulin induces in

flammation, which can progress and cause arterial stiffness, high blood pressure, Metabolic Syndrome, obesity, and also heart disease. Longevity has been associated with lower insulin levels. The below trial demonstrates the direct relationship in 18-year old men between fasting insulin and the existence of cardiovascular markers. The curves for low or no GI foods have no peaks and in comparison are relatively flat. Without a surge in insulin, inflammation is kept at bay. Foods with no or little GI: -- Non-starchy vegetables -- Protein (tofu, meat, fish, etc) -- Monounsaturated fat -- Omega-3 PUFA -- Saturated fat The Track Your Plaque goal for nearly all metabolic and cardiovascular goals is NORMAL. Therefore the optimal range for insulin is as low as possible less than 5 10 mIU/L. The goal for glucoses pre-meal is less than 83 (=4.6mmol/L) and after meals less than 110 to 120 (=6.1 to 6.67mmol/L).
Relationship between fasting insulin and cardiovascular risk factors is already present in young men: the Verona Young Men Atherosclerosis Risk Factors Study. Bonora E, et al. Eur J Clin Invest. 1997 Mar;27(3):248-54. The associations between fasting plasma insulin concentration and risk factors for cardiovascular disease were examined in 979 18-year-old men participating in the Verona Young Men Atherosclerosis Risk Factors Study, a cross-sectional population-based study. Body mass index (BMI), waist-to-hip ratio (WHR), plasma triglycerides and uric acid concentrations, and blood pressure values significantly increased, and the high-density lipoprotein (HDL)-total cholesterol ratio decreased, across quartiles of fasting insulin. Total and low-density lipoprotein cholesterol, concentrations did not change significantly with the increase in fasting insulin levels. After adjustment for BMI, WHR, smoking, alcohol intake and physical activity, only plasma triglycerides significantly increased across insulin quartiles (F = 7.1; P less than 0.001). However, systolic blood pressure and uric acid were close to statistical significance (P = 0.06-0.07). Multiple linear regression

analysis confirmed that plasma insulin was independently correlated with plasma triglycerides and, to a lesser extent, with blood pressure and uric acid concentration. This analysis pointed out that BMI was a stronger independent predictor of all cardiovascular disease risk factors than fasting insulin. When subjects were categorized according to the number of metabolic and haemodynamic disorders occurring within the same individual, subjects with multiple disorders (i.e, three or four) had higher plasma insulin levels than those with none or few disorders, even after adjusting for BMI, WHR and behavioural variables (F = 4.0; P less than 0.01). These results indicate that hyperinsulinaemia is already associated with a cluster of cardiovascular disease risk factors in young adulthood, the strongest independent association being with plasma triglycerides. PMID: 9088862

Movement with a little intensity, vitamin D/A/E/K, fish oil, seafood/grassfed meat, omega-3 eggs, wheat-free (semidairy/legume-free), low carb is the only way to go. It's not hard. At ALL. In fact, it's purely incomprehensibly curious to NOT engage in this T.Y.P. HEDONIA-lifestyle.

Plaque, Plaque, and... More Plaque Reversal

"Remodelling of alveolar bone involves interaction between osteoblasts and osteoclasts. Osteoblasts, under the influence of osteotropic hormones (vitamin D3, PTH and retinoic acid), produce MMPs which appear to function in the removal of soft tissue that precludes access of osteoclasts to the mineralized tissue surface.... Although there is strong evidence for the involvement of MMPs in the resorption of bone and in the inflammation-mediated destruction of periodontal tissues, the role of MMPs in the remodelling of mature soft connective tissues remains equivocal."
Sodek J, Overall CM. Matrix metalloproteinases in periodontal tissue remodelling. Matrix Suppl. 1992;1:352-62. Review. PMID: 1480060

------------------------

Boyd LD, Lampi KJ. Importance of nutrition for optimum health of the periodontium. J Contemp Dent Pract. 2001 May 15;2(2):36-45. Review. PMID: 12167932 Link HERE *good review*

Figure. Activation mechanisms of MMP-2. The full-length MMP-2 can be activated in two ways. Proteolytic activation of MMP-2 by MT1-MMP/TIMP or by other proteases occurs by removal of the autoinhibitory propeptide domain (left arrow) resulting in an active truncated MMP-2. The presence of oxidative stress (ONOO-) and cellular glutathione (GSH) causes the S-gluathiolation of the critical cysteine residue in the propeptide domain, disrupting its binding to the catalytic Zn2+ ion, resulting in an active full-length enzyme. MMP, matrix metalloproteinase; ONOO-, peroxynitrite; TIMP, tissue inhibitor of metalloproteinase. Chow AK, et al. Acute actions
and novel targets of matrix metalloproteinases in the heart and vasculature. Br J Pharmacol. 2007 Sep;152(2):189-205.

Recently we moved and lost our housekeepers. I've been in the double-dog dumps ever since... So to say the cleaning of the house has been neglected is a very grave understatement. Last week I devoted an inordinate amount of time scouring the calcium deposits off all the toilets in the house... it took so long so I had a long time to think. Why (??!) did I wait so long? Why did I let this thing go?? The work was so much harder and and tougher than had I just kept up with routine maintenance weekly. Right? (Also have spent time weighing the benefits of hiring professionals again) My girlfriends love using CLR (above ad) but I hesitate using such a strong

cleaning solvent on the toilets not just for the environmental impact but also the corrosive effects on the pipes (not withstanding other effects such as melting my corneas and the first 2 layers of my skin -- rubber gloves are mandatory). As I was really getting into the scrubbing and facing the challenge of getting back an immaculate white and tidy bowl, I thought is this what my nazi-Dental Hygienist thinks every time she sees me as she sharpens her metal instruments for scraping tartar and plaque off the teeth? A few years ago I was diagnosed with gum disease with pockets of '4' and '5' and told that implants and antibiotic treatment et cetera might be required some day. When you have periodontal disease, extra cleanings (btw are NOT covered by insurance) and deep scaling/root planing (yes it's as nasty as it sounds) are required to control plaque with the hopes of reducing inflammation and further damage. Gum disease actually involves similar processes that atherosclerosis/heart disease involves, including destruction by excessive MMPs. On the surface of atherosclerotic plaques in our blood vessels, MMPs are found. Destabilization of plaque has been related to overactivity of MMPs. The above article demonstrates the value of vitamin D3 and vitamin A (retinoic acid) and PTH in ameliorating gum disease and correcting the balance between building (osteoblastic activity) and cutting (osteoclastic activity) of our mature gum soft tissues. Interestingly these agents, Vitamins D3 and A, also have incredible plaquebusting benefits in the Track Your Plaque program for CAD regression and eradication. Dr. Davis demonstrated the value of Vitamin D3 in shrinking plaque in coronary arterties and heart disease reversal.

My gum disease now has reversed. I've attributed all the benefits to a lowinflammatory diet (ie rich in good oils, protein, veggies and low low carb), exercise, A-N-D vitamins D3, A and high dose EPA + DHA fish oil. At the end of sumer last year, surprisingly, my lab 25(OH)D3 was extremely low (after being in the sun daily for hours with the kids at the pool). Correction of vitamin D deficiency was one component of improving periodontal disease (obtaining blood levels of 50-60 ng/ml). Happily, at my last visit to the dentist, my gums were given a clean bill of health. Nearly all the pockets were '3's and a few '4's now. The '5's had disappeared and I was told I could return to a normal bi-annual cleaning schedule again (and no more out-of-pocket cleanings). The throbbing that I once felt in the gums are gone too. Other MMP inhibitors include Doxycline (part of the tetracycline family of drugs). It is a prescription drug which is used in the treatment of periodontal disease and gingival inflammation but has also demonstrated some value in atherosclerosis and preventing heart failure remodeling. PERIOSTAT is a brandname Doxycline indicated by the FDA for treatment of gum disease.

 Tessone A, et al. Effect of matrix metalloproteinase inhibition by doxycycline on myocardial

healing and remodeling after myocardial infarction. Cardiovasc Drugs Ther. 2005 Dec;19(6):38390. PMID: 16435072

Chow AK, Cena J, Schulz R. Acute actions and novel targets of matrix metalloproteinases in
the heart and vasculature. (see above Figure) Br J Pharmacol. 2007 Sep;152(2):189-205. Epub 2007 Jun 25. Review. PMID: 17592511

I wish I could stick vitamin D in all my toilets everyday... *heh* Dietrich T, et al. Association between serum concentrations of 25-hydroxyvitamin D and
gingival inflammation. Am J Clin Nutr. 2005 Sep;82(3):575-80. PMID: 16155270

Rickets -- a profound vitamin D deficiency condition which frequently involves signficant dental disease (because vitamin D plays a vital role in calcification of teeth and remodeling of soft gum tissues). Chaussain-Miller C, et al. Dentin structure in familial hypophosphatemic rickets: benefits of
vitamin D and phosphate treatment. Oral Dis. 2007 Sep;13(5):482-9. PMID: 17714351

Yamamoto T. Diagnosis of X-linked hypophosphatemic vitamin D resistant rickets.

Acta Paediatr Jpn. 1997 Aug;39(4):499-502. Review. PMID: 9316300

Chaussain-Miller C, et al. Dental abnormalities in patients with familial hypophosphatemic

vitamin D-resistant rickets: revention by early treatment with 1-hydroxyvitamin D. J Pediatr. 2003 Mar;142(3):324-31. PMID: 12640383

Dental insurances allow one extra covered dental cleaning during pregnancy. Studies show that the pregnancy-state increases the risk of periodontal disease (likely secondary to cortisol, inflammation, insulin? vitamin D and EPA/DHA deficiency? I would presume). Prevention with an extra cleaning is therefore now advocated. Isn't that interesting? Pregnancy may significantly deplete vitamin D stores (unless replenished) -- in order to construct enough progesterone and estrogen which are also steroidal hormones for supporting the pregnant state. Both pregnancy and lactation also reduce the mother's stores of EPA+DHA in her brain and heart in order to supply the growing fetus/baby's brain and heart. Did you know that a baby's brain is 70% of its birth weight? And did you know that breastmilk is a rich source of 'fish oil' EPA + DHA ! This researcher believes that maternal imprinting can affect CAD risk later in life. By not consuming enough good oils during conception and pregnancy, are we affecting our children later in life? He strongly believes fish oil may protect and even prevent CAD and diabetes in children when maternal EPA and DHA are adequately provided. Das UN. A perinatal strategy to prevent coronary heart disease. Nutrition. 2003 Nov-Dec;19(11-12):1022-7. Review. PMID: 14624957

 Cern H, et al. Acta Univ Palacki Olomuc Fac Med. 1990;125:173-9. Periodontium and vitamin
E and A in pregnancy.

The evaluation of the clinical condition of periodontium by means of the epidemiological indexes and the level of oral hygiene in two weeks intervals in the course of physiological pregnancy in 39 women in good general health revealed the maximum of inflammatory changes of periodontium in the 8th month of pregnancy with the amelioration shortly before delivery. Simultaneous follow-up of the physiological levels of vitamin E and A in four weeks intervals showed the decline of the mean levels of both vitamins in the course of the 8th month and their marked elevation shortly before delivery; therefore remains questionable, if this elevation reaching over their physiological range, contributes to the amelioration of the condition of periodontium observed at the same time. PMID: 2150274

Phenytoin is a drug that increases the liver metabolism of certain drugs and hormones, including Vitamin D and Vitamin A. Seizure and other individuals taking Phenytoin can be at risk not only for osteoporosis but also gum disease (and heart disease and many over conditions) due to subsequently low vitamin D levels. (Isotretinoin is a synthetic vitamin A) Norris JF, Cunliffe WJ. Phenytoin-induced gum hypertrophy improved by isotretinoin. Int J
Dermatol. 1987 Nov;26(9):602-3. No abstract available. PMID: 2965113

Lucchesi JA, et al. Severe phenytoin-induced gingival enlargement associated with

periodontitis. Gen Dent. 2008 Mar-Apr;56(2):199-203; quiz 204-5, 224. PMID: 18348382

Hall EE. Prevention and treatment considerations in patients with drug-induced gingival
enlargement. Curr Opin Periodontol. 1997;4:59-63. Review. PMID: 9655022

Sobaniec H, et al. Antioxidant activity of blood serum and saliva in patients with periodontal
disease treated due to epilepsy. Adv Med Sci. 2007;52 Suppl 1:204-6. PMID: 18229666

Vitamin A is also helpful for reversing gum disease in a condition called PapilonLefevre syndrome. Nazzaro V, et al. Papillon-Lefvre syndrome. Ultrastructural study and successful treatment
with acitretin. Arch Dermatol. 1988 Apr;124(4):533-9. PMID: 2965550

When I think about inflammation and the crucial role fish oil plays in maintaining healthy hearts and minds.... I am not shocked to find out it also regulates healthy gums and oral health. Friends on the TYP forum on the other hand will be shocked that I've reduced my dose of fish oil (slightly) since our family started drinking grass-raised cow milk which is rich in EPA+DHA, CLA, vitamins A D3 E and K2. I love fish oil for all its amazing benefits. Here is more evidence for its healing properties on gingival inflammation (and the hypothesized relationship with vascular inflammation).

 Fish oil reduces tooth loss mainly through its anti-inflammatory effects?
Hamazaki K, et al. Med Hypotheses. 2006;67(4):868-70.

Competing at several steps of arachidonic acid metabolism, n-3 fatty acids reduce production of highly active prostaglandins and leukotrienes and exert anti-inflammatory effects. They are also experimentally shown to be anti-osteoporotic. Periodontitis is responsible for most tooth loss in adult populations. If enough n-3 fatty acids are provided, periodontitis with alveolar bone resorption may be controlled, and tooth loss may be prevented. In fact, n-3 fatty acid administration lowered prostaglandin E(2) production, tooth movement and alveolar bone resorption in animal experiments. Aggression, which may be related with tooth loss, was also controlled with fish oil. Our cross-sectional data supported our hypothesis. We recruited 256 men (22-59 y of age) and 95 women (22-66 y), counted the numbers of their remaining teeth, and analyzed the fatty acid composition of the total phospholipid fraction of RBCs. The beta-coefficient of the numbers of remaining teeth and EPA concentrations in the fraction was 0.89 (per 1% EPA, p=0.007) after adjustment for 9 possible confounding factors. Long-term intervention studies with fish oil planned in the future should be able to test our hypothesis by just adding another very simple endpoint in those studies: tooth loss during the intervention period. This hypothesis may explain the linkage between periodontitis/tooth loss and coronary heart disease. PMID: 16759817

Campan P, et al. [Polyunsaturated omega-3 fatty acids in the treatment of experimental

human gingivitis] Bull Group Int Rech Sci Stomatol Odontol. 1996 Feb-Mar;39(1-2):25-31. French. PMID: 8720373 Kesavalu L, et al. Omega-3 fatty acid effect on alveolar bone loss in rats. J Dent Res. 2006 Jul;85(7):648-52. PMID: 16798867

Kesavalu L, et al. Omega-3 fatty acid regulates inflammatory cytokine/mediator messenger

RNA expression in Porphyromonas gingivalis-induced experimental periodontal disease. Oral Microbiol Immunol. 2007 Aug;22(4):232-9. PMID: 17600534

Requirand P, et al. Serum fatty acid imbalance in bone loss: example with periodontal
disease. Clin Nutr. 2000 Aug;19(4):271-6. PMID: 10952799

Iwami-Morimoto Y, Yamaguchi K, Tanne K. Influence of dietary n-3 polyunsaturated

fatty acid on experimental tooth movement in rats. Angle Orthod. 1999 Aug;69(4):365-71. PMID: 10456605

Nutritional factors play the same important roles in parallel organs in our body. Perhaps proper vitamins/food and fish oil everyday will not only keep the doctor away... But also my nazi-hygienist! :) If only the same were true for all other types of housekeeping. (Thanks go out to Mr.California for his super-RICH ideas. You deserve an 'S'

emblazoned on your chest for sharing your fascinating cardiovascular-related thoughts and insights.)

Passion for Eradication

(Part One) Why does TYP (Track Your Plaque) work? Several components of the program demonstrate success where 'conventional' therapy stops short. "Why does conventional therapy stop short?" is also a good question. I've pondered this... and really have few answers. Some of the best, brightest minds work on improving conventional peer-reviewed consensus guidelines. Is the mob mentality massively misinformed? I dunno... However history demonstrates that the herd happens to be often wrong when quantum leaps of thinking and theories occur... (as in playing with lead leads to retardation, H. pylori causes cancer, 'the earth is round', energy travels at the speed of light, e=mc2, etc). Unfortunately, evidence-based medicine requires clinical trials. How much resources are required for trials? Well, for a good RCT (randomized controlled trial) much much much LETTUCE $$$$$$$ is mandatory. Without deep pockets from Pharma and good favor from the NIH, few can achieve the outcomes typically generated from Pharma. This is currently a sad reality for science. And a minor obstruction for progress? On the blogs and TYP website, members consistently report drops in EBT scan scores and improvement in all their lipid and lab measurements. I am always impressed by the dramatic decrease in plaque-growing risk factors like lipoprotein(a) and other factors that are achieved on a frequent basis. In a soon to be released version (I call it 'TYP 2.0'), members can share (if they choose) their scan changes and lab results (likened to myspace/facebook....). The value is that we often learn from each other--both mistakes and achievements. What does TYP track? ---periodic scans ---lab monitoring ---frequent fingerstick monitoring (glucose, lipids, etc) Why is tracking crucial?

Because plaque growth is multi-factorial. Like soccer or football, both offensive as well as defensive strikes are necessary to effectively eradicate plaque. Would you go into a competitive sports match without a good game plan? Without a coach? Without knowing who you are playing against? There are a few universal truths out there. I know that I'm more preoccupied with my NEXT meal... than my 'last meal'. Fugguhdabout my MTV ! I want my F O O D N E T W O R K !!!! As a nation (I am not alone), we care more about food than heart protection. I'm guilty... I can't resist Giada . . . and her RACK . . . of lamb. Or Tyler . . . and his BEEF, C A K E recipes!! Or Nigella and her luscious TARTS ! And naked chef Jamie and his homegrown pumpkins Although I pay for car insurance, I still regularly pay out of pocket for its maintenance. Mainly out of fear as well. Will my car manufacturer's warranty be voided if I dare get my oil changes at a non-Honda dealership?! But are there really any guarantees? When I first delved into the waters of TYP... I was frankly S H O C K E D. I trolled PubMed and found nearly hundreds of studies that backed up every facet of the TYP strategy. How did Dr. Davis assemble his plan???!! The TYP program is the only program of the many I've investigated over the years which offers complete protection of the heart, where unfortunately current conventional therapies still are short. Our National Treasure is... our DR. Davis. He appears to love ciphers and mysteries. He (and his team) are constantly working on the puzzle of what grows plaque and how to effectively and maximally eradicate it for a lifetime. Here is actually one of my favorite websites which defines treatment across the United States for all endocrinology issues. The AACE was only created a few yrs ago (1991 to be exact) but they are highly advanced and respected. The diabetes lipid guidelines are a little more updated than the dyslipidemia and atherogenesis guidelines--they list the factors that TYP targets-- and offer some solutions (see page 44) but again a strategy that has totalitarian striking front against plaque is lacking (partly again due to a paucity of highly-funded RCTs). Where does current conventional therapy lead us? It is a fact that statins do work. See pg 43-45. Any

statin will reduce the risk of a first or second coronary event by 22 to 55% in 3 to 5 yrs (of a clinical trial). That is decent heart protection. But, what about the rest of the 45 to 78% ?? Actually, I am very grateful for the first landmark trials using statins. Pravastatin (from Bristol Myers) was the FIRST and therefore created the history and body of evidence that we have so far. As mentioned earlier, trials are expensive to run (and with the statistician being the most highly paid *ha haaa*). What the trials really have demonstrated is that the course of heart disease can not only be changed, heart protection is a STRONG possibility with adjunct therapy. In TYP, heart protection is in fact not only a possibility or faint dream, it's a reality. It's reliable. (Not something the fairy godmother promised) My mechanic can't even guarantee that!

Passion For Eradication: Part Deux

Why does TYP (Track Your Plaque) work? (Part 2) Seminal articles published much earlier than Dr. Davis Track Your Plaque tome provided a framework for which success could be elaborated upon... yet none of these progressively written testaments yielded solid, concrete solutions such as Dr.Daviss TYP program. The program he devised is actually dynamic.... changing with progress, newly eludicated outcomes and observations from the literature and experience. Constantly evolving and improving the program, Dr. 'D' shares his thoughts liberally on his HeartScanBlog as well as on comprehensive updates on the TrackYourPlaque website. Heart disease is being reversed on a daily basis with his powerful TrackYourPlaque plan. Members and participants (and myself) often wonder on the TYP forum and HeartScanBlog when will Dr. Davis be awarded the Nobel... The coronary risk factors have all been discovered and discussed in major medical journals by well-known experts in the field for a decade now, but a complete package of viable solutions (and manners of identification of heart disease) have seemed to fail to come to fruition in national consensus guidelines that would effectively improve care in primary and secondary cardiovascular disease prevention. Why?

Beyond bandaid-statins and common coronary surgeries, which do little to correct underlying disease processes, what exists that actually works? Why is coronary artery disease still the #1 killer in America... and strokes #3? Why aren't these stats changing (and seem to get worse, especially for women)? Why is CAD not being broadly reversed with the huge resources and high-tech approaches currently available in our great country?? Because Dr. Davis emphasizes the use of a convenient, low-radiation diagnostic tool --- the EBT heart scans --- to guide and dictate therapy, the only plan and protocol for effective plaque reversal that has a true TRACK record of success is of course TY-P. Is seeing is not believing when plaque is present? Usually unfortunately... affirmative... (unless you're symptomatic with anginal pain or erectile dysfunction (future blog topic)). TYP optimizes each and every risk factor identified at this time (in addition to 'new' risk factors that Dr.Davis may find emerging later). Predicting potential penetrating plaque-producers (now... say that 10x) is the key to knowing what elements you are dealing with. These are subsequently quenched... For a lifetime
Proatherogenic mechanisms and progression pattern from initial artery injury through clinically manifest disease

Lists of potential CAD risk factors were discussed for the past 10 years:
Pahor M, Elam MB, Garrison RJ, Kritchevsky SB, Applegate WB. Emerging noninvasive biochemical measures to predict cardiovascular risk. Arch Intern Med. 1999 Feb 8;159(3):237-45. See diagram (above) and summary of CV risk factors (below)

Oparil S, Oberman A. Nontraditional cardiovascular risk factors. Am J Med Sci. 1999 Mar;317(3):193-207. Frishman WH. Biologic markers as predictors of cardiovascular disease. Am J Med. 1998 Jun 22;104(6A):18S-27S. Harjai KJ. Potential new cardiovascular risk factors: left ventricular hypertrophy, homocysteine, lipoprotein(a), triglycerides, oxidative stress, and fibrinogen. Ann Intern Med. 1999 Sep 7;131(5):376-86. Gonzalez MA, Selwyn AP. Endothelial function, inflammation, and prognosis in cardiovascular disease. Am J Med. 2003 Dec 8;115 Suppl 8A:99S-106S.

These physicians above all have brought up a variety of coronary risk factors which are strong nasty plaque-builders. They did an immense service by listing new variables in the equation for heart disease. In addition, Drs. McCarron and Oparil et al demonstrated in a controlled trial that a comprehensive nutrition program was spectacularly powerful in lowering BP, insulin, glucose, LDL, LDL/HDL ratio, homocysteine and other drivers of heart disease. McCarron DA, Oparil S, et al.
Comprehensive nutrition plan improves cardiovascular risk factors in essential hypertension. Am J Hypertens. 1998 Jan;11(1 Pt 1):31-40.

The below publication from 2002 was produced from the AACE , the venerable group of brilliant forward-thinking experts which I mentioned earlier (updated

recently in 2006 to take into account the Heart Protection Study and other landmark trials). The American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the Diagnosis and Treatment of Dyslipidemiaand Prevention of Atherogenesis 2002 (Amended Version) The first thing that blew me away about these guidelines was the demonstration of the utilization of CT scan scoring is on Table 16 on p.195 for an evaluation of a CAD patient case study (although I believe truly 'normal' is a zero score). Back in 2002 even CT scan results provided value to the AACE as a standard of practice for detecting high risk heart disease and the presence of plaque. Wow. Isnt that interesting? Back in 2002... This is why I like the AACE Personally, in my opinion the pictures also are fantastic. Please see if you're into the pathogenesis of pro-atherogenic lipoproteins:

Fig 1, 2, 3 on p.175 Fig 4 on p.176 Fig 5 on p.180

The AACE also identified the below Risk Factors for Coronary Artery Disease (Table S-1 on pg.166) which enumerate the same ones listed in the above medical journal articles.
Coronary Risk Factors High total cholesterol or LDL-C Small, dense LDL Low HDL-C Hypertriglyceridemia Advancing age Type 2 diabetes mellitus Hypertension Obesity Cigarette smoking Family history of CAD Increased levels of Lp(a) lipoprotein Factors related to blood clotting, including increased levels of fibrinogen and PAI-1 Hyperhomocysteinemia Certain markers of inflammation, including C-reactive protein

And this is why I really REALLY like the AACE:

1. Other risk factors for heart disease were additionally identified -- PCOS, hypothyroidism, SLE/lupus, Cushing's disease, etc (common theme: inflammation, insulin resistance) 2. A moderate, lower-carb diet is favored over a typically AHA high-carb diet (on p.196; first 1-2 paragraphs) for a patient with elevated triglyerides (which is 50% of all Americans according to the NHANES data, although I'd predict that would probably be about 70% now) 3. Can the AACE top their already prescient anti-atherogenesis guidelines?? Absolutely... A brief cost-benefit analysis (on p.196 Fig 6) of the resources conserved when cardiac events, surgeries and hospitalizations are successfully averted with lifestyle/medical/nutritional therapy. Does this remind you of Heart Hawk's incredible cost-analysis report??

The AACE are surprisingly one of the most progressive group of classic, systemic heart disease and prevention experts (btw they are not Cardiologists wonder why is that?). So who... can possibly... trump the AACE?? Who seems to be scientifically... divinely inspired... Dr. Davis certainly seems to possess otherworldy genius. Not only has he assembled the best plan to strategically reduce all plaque growth and eradicate plaque by tackling each and every one of these risk factors identified so far (and then some!), but he has also taken the art of medicine to a practical and do-able level for any person concerned about heart disease. By encouraging discussion, empowerment and pro-activism, the solutions are transparent and T-YP-ically reachable. And the community to fully engage in the TYP program is about to be advanced to the next level... TYP 2.0! Can you find that elsewhere I must ask? A brief review of the TYP Strategy: Plaque-Builders
----------Blood pressure

TYP Strategy
--------------------------

TYP Goals To Reduce EBT Score

-----------------

L-Arginine, Vitamin D3, exercise, Normalization: BP = IBW, weight loss, carb restriction, 110/70 Pulse 60 cocoa extracts, etc Supplementation of D3 (cholecalciferol in oil gel capsules) Wheat elimination, carb Normalization: 25(OH)D3 = 60 ng/ml Small LDL less than

Vitamin D3 Deficiency Presence of Small LDL

restriction, Niacin, Vitamin D3, Oat bran, Intermittent Fasting, etc Wheat elimination, increased intake good oils/fats, high dose fish oil, Vitamin D3, Vitamin B3 (niacin), etc

10% (LDL less than 60 mg/dl)

Elevated TG

TG less than 60 mg/dl

Low HDL

See above, strength training, carbohydrate restriction, dietary oils/fats, etc

HDL 60 mg/dl or higher

Lipoprotein(a)

See Lp(a) TYP Report, Niacin, Vitamin D3, high dose fish oil, Carb restriction, L-carnitine, Normalization: Lp(a) less coQ10, raw nuts, DHEA, than 30 mg/dl Estrogen, Testosterone, adequate good oils/fat, etc Normalization: Vitamins B6, B12, Folic acid, Homocysteine less Wheat elimination, Estrogen, etc than 8.0 Aspirin, fish oil, raw nuts, carb restriction, exercise, smoking cessation, etc Normalization

Homocysteine

Fibrinogen

Normalization: Wheat elimination, Carb Abnl Glucose, Premeal glucose less restriction, Exercise, IBW, Vitamin Hyperinsulinemia,Type 2 than 85 mg/dl; Insulin D3, high dose fish oil, raw nuts, Diabetes, Type 1 Diabetes less than 5-10 uIU/L Magnesium, Estrogen, etc (A1C 5.0%) Metabolic syndrome (including Central Obesity, NAFLD, Cardiac Steatosis, Same As Above PCOS, Acanthosis Nigricans) Estrogen Deficiency Testosterone Deficiency Antioxidant Deficiencies Thyroid Disorder Normalization: ALT, AST less than 40 (Normal Echo)

Bio-identical HRT, Vitamin D3, etc Normalization Replacement, Vitamin D3, etc Normalization

Diet/supplementation of Vitamin Normalization K2, C, E, A, D3, etc Replacement, Vitamin D3, Normalization: TSH 0.2

Magnesium, Calcium, etc

- 2.0 mIU/L

Oxidative Stress, Inflammation

Above strategies, exercise training, yoga, meditation, Natural Vitamins, improvement of Normalization: CRP sleep (quantity, quality), mental less than 3.0 stress reduction, high dose Vitamin O, etc Normalization: Cr less BP and glucose normalization, than 0.8-1.0 Vitamin D3, high dose fish oil, Microalbuminuria less address Lp(a)/Homocysteine, etc than 20 ug/mg Normalization: Prevention of dissection and expansion See TYP

Chronic Kidney Disease

Abdominal/Thoracic Aortic All the above, BP normalization, Aneurysm, Valvular Vitamin D3, etc Disease Other CAD Risk Factors Identified under TrackYourPlaque.com

Who are the true warriors of the earth? Those with Lp(a)?

--Individuals resistance to common infections, colds, cancers --Postmeno women (reduced estrogen) --African Americans and Africans (natives, fishing tribes along the Nile, and Saharan residents including Cleopatra's descendants)

Are the Lp(a) carriers superior with their resistance against scurvy, vitamin C deficiency, superiority against cancers/infections? Are these the mythical warrior race? The Amazonians? Do they survive short-term life-sentences with no consequences...as long as they follow a 'warrior lifestyle'? --meat, milk, blood, organ meats, fish, seafood?

--no grains? no refined carbs... ? --frequent high intensity battle, training? --frequent intermittent fasting? --stress control -- control of Type A and Type D tendencies? It would appear so to me... WCCA guy brings up Rath's theory on the TYP forum regarding multiple DNA breaks with scurvy and any other nutritional deficiencies to increase the DNA variations that would bring about EVOLUTION. Tx for Lp(a) per Rath: --high dose vit C (ascorbic acid) --Proline --Lysine Where are sources of Vitamin C if vegetation and tubers are scarce? --adrenal glands/duodenum -- the highest source of Vitamin C found in nature in the animal kingdom Where are the food sources rich in Lysine? --abalone, fish, caviar, mollusks, meat, eggs, pork, poultry, soy (tofu, defatted soy flour, isolated soy protein), eggs, fermented dairy (particularly parmesan), nuts, spirulina, fenugreek seed, soaked legumes, cheese (blue, camembert, gruyere -yea stinkier the better) Unfortunately when Lp(a) is uncontrolled, dysregulation of vascular beds occurs, ie ED, retinopathy, neuropathy, retinopathy, retinal strokes, carotid disease, coronary disease, peripheral vascular disease and erectile dysfunction. Lp(a) may be uncontrolled with non-adherence with a warrior-race lifestyle ala '300' movie about love & war -- where less than 10% BF-RIPPED-low Lp(a)-abs 'n pecs dominate -enjoy Lena Headey uncensored... or Breaking Benjamin's BLOW ME AWAY)
Egyptian researchers: El-Latif MA, Makhlouf AA, Moustafa YM, Gouda TE, Niederberger CS, Elhanbly SM. Diagnostic value of nitric oxide, lipoprotein(a), and malondialdehyde levels in the peripheral venous and cavernous blood of diabetics with erectile dysfunction. Int J Impot Res. 2006 Nov-Dec;18(6):544-9. Epub 2006 Apr 20. PMID: 16625232 More insights from researchers on Egyptian populations demonstrating a difference in male v. female babies: AbouGhalia AH, Khater LM, Abd El-Wahed MA, El-Badrawy MF. Lipoprotein (a) and lipid profile in neonates from mothers with three different types of diabetes mellitus.

Clin Biochem. 2003 Oct;36(7):563-9. PMID: 14563451 MetSyn also shown to be dangerous combination with Lp(a) as recognized by this researcher from Cairo, Egypt: Wassef GN. Lipoprotein (a) in android obesity and NIDDM: a new member in 'the metabolic syndrome'. Biomed Pharmacother. 1999 Dec;53(10):462-5. Review. PMID: 10665339 Ancient wheat afflicted ancient Egyptians as it afflicts us now: Nerlich AG, Rohrbach H, Zink A. [Paleopathology of ancient Egyptian mummies and skeletons. Investigations on the occurrence and frequency of specific diseases during various time periods in the necropolis of Thebes-West] Pathologe. 2002 Sep;23(5):379-85. Epub 2002 Aug 21. German. PMID: 12376865

Valentine RJ, Grayburn PA, Vega GL, Grundy SM. Lp(a) lipoprotein is an independent, discriminating risk factor for premature peripheral atherosclerosis among white men. Arch Intern Med. 1994 Apr 11;154(7):801-6. PMID: 8147686 Valentine RJ, Kaplan HS, Green R, Jacobsen DW, Myers SI, Clagett GP. Lipoprotein (a), homocysteine, and hypercoagulable states in young men with premature peripheral atherosclerosis: a prospective, controlled analysis. J Vasc Surg. 1996 Jan;23(1):53-61, discussion 61-3. PMID: 8558743 Tesch GH. (Australian kidney dept -- excellent -- oxLDL and Lp(a)-- immune system brilliance) Role of macrophages in complications of type 2 diabetes. Clin Exp Pharmacol Physiol. 2007 Oct;34(10):1016-9. Review. PMID: 17714088 Cheng SW, Ting AC, Wong J. Lipoprotein (a) and its relationship to risk factors and severity of atherosclerotic peripheral vascular disease. Eur J Vasc Endovasc Surg. 1997 Jul;14(1):17-23. PMID: 9290555 Dahln GH, Srinivasan SR, Stenlund H, Wattigney WA, Wall S, Berenson GS. The importance of serum lipoprotein (a) as an independent risk factor for premature coronary artery disease in middle-aged black and white women from the United States. J Intern Med. 1998 Nov;244(5):417-24. PMID: 9845858 Deepa R, Mohan A, Rema M, Haranath SP, Saravanan G, Mohan V. Lipoprotein(a) in South Indian type 2 diabetic subjects in relation to diabetic vascular complications. J Assoc Physicians India. 2002 May;50(5):657-61. PMID: 12186119 Paultre F, Pearson TA, Weil HF, Tuck CH, Myerson M, Rubin J, Francis CK, Marx HF, Philbin EF, Reed RG, Berglund L.

High levels of Lp(a) with a small apo(a) isoform are associated with coronary artery disease in African American and white men. Arterioscler Thromb Vasc Biol. 2000 Dec;20(12):2619-24. PMID: 11116062 Parlavecchia M, Pancaldi A, Taramelli R, Valsania P, Galli L, Pozza G, Chierchia S, Ruotolo G. Evidence that apolipoprotein(a) phenotype is a risk factor for coronary artery disease in men les than 55 years of age. Am J Cardiol. 1994 Aug 15;74(4):346-51. PMID: 8059696 Bostom AG, Cupples LA, Jenner JL, Ordovas JM, Seman LJ, Wilson PW, Schaefer EJ, Castelli WP. Elevated plasma lipoprotein(a) and coronary heart disease in men aged 55 years and younger. A prospective study. JAMA. 1996 Aug 21;276(7):544-8. PMID: 8709403 Jenkins AJ, Rowley KG, Lyons TJ, Best JD, Hill MA, Klein RL. Lipoproteins and diabetic microvascular complications. Curr Pharm Des. 2004;10(27):3395-418. Review. PMID: 15544524 Asakawa H, Tokunaga K, Kawakami F. Comparison of risk factors of macrovascular complications. Peripheral vascular disease, cerebral vascular disease, and coronary heart disease in Japanese type 2 diabetes mellitus patients. J Diabetes Complications. 2000 Nov-Dec;14(6):307-13. PMID: 11120454 Ghorbanihaghjo A, Javadzadeh A, Argani H, Nezami N, Rashtchizadeh N, Rafeey M, Rohbaninoubar M, Rahimi-Ardabili B. Lipoprotein(a), homocysteine, and retinal arteriosclerosis. Mol Vis. 2008 Sep 15;14:1692-7. PMID: 18806883 Funatsu H, Shimizu E, Noma H, Mimura T, Hori S. Association between serum lipoprotein (a) level and progression of non-proliferative diabetic retinopathy in Type 2 diabetes. Acta Ophthalmol. 2008 Aug 11. [Epub ahead of print] PMID: 18700887

Melatonin has been on my mind...ever since Dr. D got me turned on to it here a little while ago. I know several people who take it and TOTALLY swear by it for insomnia. How can this hormone have such far-reaching benefits and effects? It's used for: --jet lag --inducing hGH secretion --hypertension --breast cancer prevention --oxidative damage protection --insomnia --vasculature un-responsiveness (relaxation/constriction with ACh or adrenaline) --migraine prevention

--modulation of behavior and sleep patterns in autistic children --natural aromatase inhibitor -- prevents excessive conversion of Testosterone to Estradiol (E2) and Androstenedione to Estrone (excessive Estrone (E1) is not good -'storage' form of estrogen in our adipose tissues and linked to promotion of cancer...and ??perhaps heart disease?) Melatonin also is the master hormone behind skin changes in amphibians and reptiles. How about us humans? You know how teenagers get all moody and starting staying up late and waking up late? And how they may transform from sweet kids to stinky Twilight sulkiness? Melatonin drops as sexual maturation occurs and this may lead to disrupted sleep cycles. This researcher and author of the textbook Dev Bio notes that Melatonin is the suspected hormone that allows human metamorphosis to occur: "The various morphological and behavioral changes of puberty are due to the actions of these hormones on the various target tissues. As in metamorphosis, there appears to be a maturation-inhibiting hormone whose activity decreases to permit the reactivation of development. In humans, this hormone is probably MELATONIN, whose serum concentration decreases as that of LH rises (Waldhauser and Dietzel, 1985)."

So who may experience dysregulation of Melatonin? Which came first...the chicken or the egg? Dysregulation of the hypothalamus/pituitary/pineal axis with wheatassaults, in utero maternal vitamin D deficiency and/or neonatal/developmental EPA-DHA deficiency? Are we epigenetically pushing our species into extinction? The medical literature shows that many types of individuals are deficient in melatonin in the diurnal secretion that normally occurs at night -- in the pitch black inkiness of the night as nature intended (of course unless the full moon is shining). Normally melatonin starts to rise at 7pm and peaks at 2am then gradually falls again by dawn. Seasonal rhythms obviously exist also. Anciently controlled tides that we may not even be conscious of. In Scotland, scientists have recently shown how "Melatonin acts directly on anterior-pituitary cells, and these then relay the photoperiodic message back into the hypothalamus to control neuroendocrine output...(to trigger increases in TSH which subsequently signals activation of T3 (active thyroid hormone from T4) for increased metabolism and reproduction)...In mammals this provides the missing link between the pineal melatonin signal and thyroid-dependent seasonal biology (Hazlerigg Curr Biol. 2008 Aug 5;18(15):114752). --Autistic spectrum children -- they tend to also display a genetic polymorphism, a

deletion for the gene encoding the last enzyme for the making of Melatonin --Individuals with coronary artery disease --Type 2 diabetes with cardiac autonomic neuropathy (stiff heart rate variability (HRV)) --Wernicke-Korsakoff syndrome -- ie, brain-damage due to malnourishment -- seen in gastric bypass and alcoholics --Sleep deprived individuals, swing shift workers, travel involving time zone shifts --Hyperthyroid, hypothyroid (higher melatonin secretion but also higher elimination in the urine found) --Environmental lighting conditions, drugs and other disease states: "Patients with alcoholism, migraine, postoperative pinealoma, panhypo-pituitarism, hereditary dystonia and schizophrenics on propranolol exhibited a decreased amplitude of their diurnal rhythm of melatonin." (Wetterberg L J Neural Transm Suppl. 1978; (13):289-310.) --Fibromyalgia 31% less compared with healthy controls --Alcohol consumption lowers Melatonin secretion 20% (HHHhhhmmmm...Patrone's+PEET*s apparently is a bad combo for my melatonin??? darn; don't worry -- light intake's fine) --Obstructive sleep apnea

We are certainly learning a lot about the how all hormones are inter-related in the body. Like life, one disjointed connection can lead to impaired connections downstream. Are there ways to repair and strengthen the misconnected parts? I'm here at TYP...so I certainly believe in the plasticity of our bodies (and I aint referring to the wonders of silicon *wink*). Thoughtful-mindfulness...meditation, prayer, yoga, tai-chi, massage, day-spa visits all achieve a level of control that is exerted on our 'third eye', the tiny pineal gland (see above; courtesy of here). I read a TIME magazine article ~2-3 yrs about how Buddhist monks were able to activate and light up parts of the brain on PET scans that normally are not associated with neural activity. They meditated (and according to the Dalai Lama teachings that I've read, this involves heightened awareness and enlightened empathy). Is this related to the Pineal Gland? Are there mechanisms that exist for synergizing our Pineal (found in the 3rd ventricle of the brain) with the rest of the brain, body and our deep unconsciousness? (like syncing an iPod to the computer?)

I dunno...but certainly other forms of meditation have been shown in small trials to result in significantly higher melatonin secretion from the Pineal Gland. Like a power nap an adequate night's slumber, how can plain old brain-power power up and protect our Pineal Gland? Apparently in very very very potent ways...! Maybe this justifies my addiction to day spas and yoga? Tranquility is so super addictive. Are we hard-wired for tranquility? Yes, I believe so once we are plugged into it.

Plaque-Busting Benefits of Yoga and Meditation --"Experienced meditators practising either TM-Sidhi or another internationally well known form of yoga showed significantly higher plasma melatonin levels in the period immediately following meditation compared with the same period at the same time on a control night." (Sali A. Acute increases in night-time plasma melatonin levels following a period of meditation. Biol Psychol. 2000 May;53(1):6978.) --"Yogic practices for 3 months resulted in an improvement in cardiorespiratory performance (orthostatic tolerance, heart rate, BP, respiratory rate, dynamic lung function (such as forced vital capacity, forced expiratory volume in 1 second, forced expiratory volume percentage, peak expiratory flow rate, and maximum voluntary ventilation) and psychologic profile. The plasma melatonin also showed an increase after three months of yogic practices. The systolic BP, diastolic BP, mean arterial pressure, and orthostatic tolerance did not show any significant correlation with plasma melatonin. However, the maximum night time melatonin levels in yoga group showed a significant correlation (r = 0.71, p less than 0.05) with well-being score. Effects of Hatha yoga and Omkar meditation on cardiorespiratory performance, psychologic profile, and melatonin secretion. Sawhney RC J Altern Complement Med. 2004 Apr;10(2):261-8.)

Coronary/Vasculature Relationship and Role of Melatonin Two publications from Northwestern med school recently reviewed the melatonin and the receptors that it binds and modulates: MT1, MT2, MT3. In one, the authors described the broad spectrum effects of Melatonin on a variety of organ systems (Masana MI Front Biosci. 2003 Sep 1;8:d1093-108. Molecular pharmacology, regulation and function of mammalian melatonin receptors). Like adrenaline (ie, NE/EPI) that binds beta- or alpha-receptors in various locations in our bodies, the end result can be inhibiting or stimulating activity; the physiological function

depends on the location of the receptors as well. Likewise with Melatonin and the MT series, location and type of receptors determines function. Melatonin receptors affect every organ system: CNS (brain), hypothalamic-pituitary-pineal-thyroidgonadal axis, cardiovascular, and immunity. The second article below describes inhibitory and activating effects of MT receptors. Functional MT1 and MT2 melatonin receptors in mammals. Dubocovich ML, Markowska M. Endocrine. 2005 Jul;27(2):101-10. Melatonin, dubbed the hormone of darkness, is known to regulate a wide variety of physiological processes in mammals. This review describes well-defined functional responses mediated through activation of high-affinity MT1 and MT2 G proteincoupled receptors viewed as potential targets for drug discovery. MT1 melatonin receptors modulate NEURONAL FIRING, ARTERIAL VASOCONSTRICTION, cell proliferation in cancer cells, and REPRODUCTIVE AND METABOLIC FUNCTIONS. Activation of MT2 melatonin receptors phase shift circadian rhythms of neuronal firing in the suprachiasmatic nucleus, inhibit dopamine release in retina, INDUCE VASODILATION and inhibition of leukocyte rolling in arterial beds, and ENHANCE IMMUNE RESPONSES. The melatonin-mediated responses elicited by activation of MT1 and MT2 native melatonin receptors are dependent on circadian time, duration and mode of exposure to endogenous or exogenous melatonin, and functional receptor sensitivity. Together, these studies underscore the importance of carefully linking each melatonin receptor type to specific functional responses in target tissues to facilitate the design and development of novel therapeutic agent. (OF COURSE! LET'S MAKE A PROFITABLE DRUG! ESP WHEN A CHEAP NATURAL ORIGINAL ALREADY EXISTS AND IS WIDELY AVAILABLE) PMID: 16217123

Coenzyme Q10 and the Ubiquinone System

I've been cleaning the house today and noticed BOY how much garbage and junk quickly accumulates. Often it's painful to face the facts... and the havoc and entropy! You know... it's like the ol' coyboys in my favorite Western movies who needed a few shots of WHISKEY to take away the PAIN when the bullets were taken out of the wounds...

YIKES. I have to admit I can't stand house cleaning. Allergic is a good word. I don't have asthma any longer (thanks to TYP and therapeutic doses of Vitamin D3) but I'm still allergic... CAN'T STAND IT. Some of my best friends and neighbors have let their 'professional' help go recently (with the increase in costs from PETROL etc)... I let mine go a year ago after we moved... Boy... can you spell M-I-S-E-R-Y...??? Occasionally I'll do this trick and invite my most Martha-Stewart-girlfriends over for dinner. I figure they can SHAME me into cleaning... of course it works and the house will be sparkling clean for about 10minutes... Unfortunately sometimes I invite my friends over and I get busy and fail to have time to clean. I just hope that I can get them liquored up and blur their vision to the dirt rings in the toilet and the dust accumulating... NNNNAAAWWWWTTTT... they DON'T IMBIBE... what was I thinkin??!

How can a family of 6 generate so much waste? And one cat? And several house spiders? For one, I've been losing some hair (though reversing after stopping my DARN synthetic hormone LNg for birth control) so... yeah go ahead make the dog comparisons... I admit I shed... Long hairs ALL OVER THE DARN HOUSE. How does our mammalian bodies handle waste and garbage? Is it pollution? Or does everything to some extent get recycled??? Co Q10 helps with recycling of crucial antioxidants and vitamins in our mitochondria and membranes. Coenzyme Q10 is a crucial component of the TrackYourPlaque program. Other benefits include: --Counters the depletion of Co Q10 that occurs with Statin use --Reduces Lipoprotein (a) 12% -- Check out the TYP Report --Recycles our natural antioxidants like Vitamin E, Glutathione, etc --Reverses heart failure --Plays an critical role in anti-aging, neuroprotection, cardioprotection and reduction in hyperinsulinemia/diabetes/MetSyn

Curr Neurovasc Res. 2005 Dec;2(5):447-59. The emerging role of coenzyme Q-10 in aging, neurodegeneration, cardiovascular disease, cancer and diabetes mellitus.Dhanasekaran M, Ren J.

Division of Pharmaceutical Sciences, School of Pharmacy, University of Wyoming, Laramie, WY 82701, USA. Coenzyme Q (ubiquinone, 2-methyl-5,6-dimethoxy-1,4-benzoquinone), soluble natural fat quinine, is crucial to optimal biological function. The coenzyme Q molecule has amphipathic (biphasic) properties due to the hydrophilic benzoquinone ring and the lipophilic poly isoprenoid side-chain. The nomenclature of coenzyme Q-n is based on the amount of isoprenoid units attached to 6-position on the benzoquinone ring. It was demonstrated that coenzyme Q, in addition to its role in electron transport and proton transfer in mitochondrial and bacterial respiration, acts in its reduced form (ubiquinol) as an antioxidant. Coenzyme Q-10 functions as a lipid antioxidant regulating membrane fluidity, recycling radical forms of vitamin C and E, and protecting membrane phospholipids against peroxidation. The antioxidant property, high degree of hydrophobicity and universal occurrence in biological system, suggest an important role for ubiquinone and ubiquinol in cellular defense against oxidative damage. Coenzyme Q-10 is a ubiquitous and endogenous lipid-soluble antioxidant found in all organisms. Neurodegenerative disorders, cancer, cardiovascular diseases and diabetes mellitus and especially aging and Alzheimer's disease exhibit altered levels of ubiquinone or ubiquinol, indicating their likely crucial role in the pathogenesis and cellular mechanisms of these ailments. This review is geared to discuss the biological effect of coenzyme Q with an emphasis on its impact in initiation, progression, treatment and prevention of neurodegenerative, cardiovascular and carcinogenic diseases. PMID: 16375724

Other illuminating references:

Ernster L, Forsmark-Andre P. Ubiquinol: an endogenous antioxidant in aerobic organisms. Clin Investig. 1993;71(8 Suppl):S60-5. Review. PMID: 8241707 [PubMed - indexed for MEDLINE] James AM, Smith RA, Murphy MP. Antioxidant and prooxidant properties of mitochondrial Coenzyme Q. Arch Biochem Biophys. 2004 Mar 1;423(1):47-56. Review. PMID: 14989264 [PubMed - indexed for MEDLINE] Mohora M, Katona E, Dinu V. Pro- and antioxidant functions of quinones in mammalian cells. Rom J Intern Med. 1999 Jan-Mar;37(1):3-14. Review. PMID: 15523940 [PubMed - indexed for MEDLINE] Albano CB, Muralikrishnan D, Ebadi M. Distribution of coenzyme Q homologues in brain.

Neurochem Res. 2002 May;27(5):359-68. PMID: 12064350 [PubMed - indexed for MEDLINE] Shults CW. Coenzyme Q10 in neurodegenerative diseases. Curr Med Chem. 2003 Oct;10(19):1917-21. Review. PMID: 12871093 [PubMed - indexed for MEDLINE] Ernster L, Dallner G. Biochemical, physiological and medical aspects of ubiquinone function. Biochim Biophys Acta. 1995 May 24;1271(1):195-204. Review. PMID: 7599208 [PubMed - indexed for MEDLINE] Littarru GP, Tiano L. Bioenergetic and antioxidant properties of coenzyme Q10: recent developments. Mol Biotechnol. 2007 Sep;37(1):31-7. Review. PMID: 17914161 [PubMed - indexed for MEDLINE] Navas P, Villalba JM, de Cabo R. The importance of plasma membrane coenzyme Q in aging and stress responses. Mitochondrion. 2007 Jun;7 Suppl:S34-40. Epub 2007 Mar 16. Review. PMID: 17482527 [PubMed - indexed for MEDLINE] Siemieniuk E, Skrzydlewska E. [Coenzyme Q10: its biosynthesis and biological significance in animal organisms and in humans] Postepy Hig Med Dosw (Online). 2005;59:150-9. Review. Polish. PMID: 15928598 [PubMed - indexed for MEDLINE] Ernster L, Forsmark P, Nordenbrand K. The mode of action of lipid-soluble antioxidants in biological membranes. Relationship between the effects of ubiquinol and vitamin E as inhibitors of lipid peroxidation in submitochondrial particles. J Nutr Sci Vitaminol (Tokyo). 1992;Spec No:548-51. Review. PMID: 1297809 [PubMed - indexed for MEDLINE] Pobezhimova TP, Voinikov VK. Biochemical and physiological aspects of ubiquinone function. Membr Cell Biol. 2000;13(5):595-602. Review. PMID: 10987383 [PubMed - indexed for MED INE] Beyer RE. An analysis of the role of coenzyme Q in free radical generation and as an antioxidant. Biochem Cell Biol. 1992 Jun;70(6):390-403. Review. PMID: 1333230 [PubMed - indexed for MEDLINE] Nohl H, Gille L, Staniek K. The biochemical, pathophysiological, and medical aspects of ubiquinone function. Ann N Y Acad Sci. 1998 Nov 20;854:394-409. Review. PMID: 9928447 [PubMed - indexed for MEDLINE] Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol. 2007;39(1):44-84. Epub 2006 Aug 4. Review. PMID: 16978905 [PubMed - indexed for MEDLINE] Nohl H, Gille L, Kozlov AV. Antioxidant-derived prooxidant formation from ubiquinol. Free Radic Biol Med. 1998 Oct;25(6):666-75. PMID: 9801066 [PubMed - indexed for MEDLINE] Merlo Pich M, Castagnoli A, Biondi A, Bernacchia A, Tazzari PL, D'Aurelio M, Parenti Castelli G, Formiggini G, Conte R, Bovina C, Lenaz G. Ubiquinol and a coenzyme Q reducing system protect platelet mitochondrial function of transfusional buffy coats from oxidative stress. Free Radic Res. 2002 Apr;36(4):429-36. PMID: 12069107 [PubMed - indexed for MEDLINE]

Shults CW. Therapeutic role of coenzyme Q(10) in Parkinson's disease. Pharmacol Ther. 2005 Jul;107(1):120-30. Epub 2005 Apr 21. Review. PMID: 15963354 [PubMed - indexed for MEDLINE] Wold LE, Muralikrishnan D, Albano CB, Norby FL, Ebadi M, Ren J. Insulin-like growth factor I (IGF-1) supplementation prevents diabetes-induced alterations in coenzymes Q9 and Q10. Acta Diabetol. 2003 Jun;40(2):85-90. PMID: 12861406 [PubMed - indexed for MEDLINE] Rauchov H, Drahota Z, Lenaz G. Function of coenzyme Q in the cell: some biochemical and physiological properties. Physiol Res. 1995;44(4):209-16. Review. PMID: 8789639

The richest food sources of natural Coenzyme Q10: --Organ meats: heart, liver, etc --Fish, seafood, mollusks --Meat: grass fed meat, poultry

Saturated Fats as Potent Anti-Atherogenic Drugs

I hope we are not still scarred by the long onslaught of ingrained sat-fat nonsense over the last few decades?

LAURIC ACID (12C MEDIUM-CHAIN SATURATED FATTY ACID) ASSOCIATED WITH RELATIVELY HIGHER HDL2b AND LOWER HDL3c In the previous entry, conclusions from the same research below was discussed. They went further and looked at the lipoprotein subfractions including HDL2b and HDL3c. Mensink et al found that the higher the phospholipid transfer protein (PLTP) activity and the lower the cholesterol ester transfer protein (CETP) activity, the higher the relative abundance of HDL2b, the regression particle, and the lower the HDL3c, a small dense atherogenic particle. Lauric acid produced the highest ratio of PLTP to CETP activity when compared with the control, palmitic or oleic diets after 6-weeks. Their assessment was "It is now clearly established that CETP and PLTP can modulate the size distribution of serum lipoprotein fractions. On the one hand, CETP can replace lipoprotein cholesteryl esters by hydrolyzable triglycerides which are derived from the triglyceride-rich lipoproteins, favoring the emergence of small-

sized LDL, pre-beta-HDL and small-sized alpha-HDL [40]. On the otherhand, PLTP has been shown to promote the formation of both pre-beta-HDL and large-sized alpha-HDL through an inter-HDL fusional mechanism [40]. In the present study, no significant differences in the size distribution of either HDL or LDL fractions were observed in sera from subjects consuming either of the three experimental diets... Despite the absence of modifications of the size distribution of HDL, significant relationships between lipid transfer activities andthe relative abundance of HDL subpopulations were observed among (INDIVIDUAL) subjects consuming the same, standardized diet. Overall, CETP correlated positively with small HDL, but negatively with large HDL, whereas opposite tendencies were observed with PLTP that correlated negatively with small HDL, but positively with the large ones (ie, HDL2b)." Variations in serum cholesteryl ester transfer and phospholipid transfer activities in
healthy women and men consuming diets enriched in lauric, palmitic or oleic acids. Lagrost L, Mensink RP, Guyard-Dangremont V, Temme EH, Desrumaux C, Athias A, Hornstra G, Gambert P. Atherosclerosis. 1999 Feb;142(2):395-402. Email for PDF.

BALANCE OF CETP AND PLTP NECESSARY Minimization and maximization, respectively, as the Mensink study showed. What are the dangers of artificially inhibiting CETP and ignoring PLTP activity? What are the dangers of raising only HDL3c (small dense atherogenic HDL) and lowering HDL2b (the regressive, large/fluffy HDL)??! The story of Torcetrapib...an extremely unhappy unending... Well...for one Pfizer is now out of the lipid-heart-disease business (Lipitor RIP 2011 when it goes generic). Read the TYP report on this CETP-inhibitor and the surprising outcome HERE. Pfizer's $20B Torcetrapib HDL-raising drug unfortunately failed big time (in low-fat, low cholesterol, low saturated fat populations). Not only was an increase of 50% in total HDL observed in humans but also coronary regression was demonstrated in animal studies. Oddly this curious drug was associated with nearly double the deaths in the single human morbidity/mortality trial. Are animal brains as functional or large as human brains? What is the purpose of cholesterol? Are

humans brains not laden with cholesterol? In fact 23% of the whole body pool of cholesterol is found in the brain and central nervous system. Although the brain only weighs 2.1% of our total weight, the cholesterol content is the highest compared with any other tissue (23 mg chol/gram). How much cholesterol is in an egg yolk? A measly ~200 mg. Barely enough to support or maintain a smidgeon of your SUPER SAVANT BRAIN. And we're told to have no more than an egg a day? Can you spell autism? Well... probably neither can the great-grandchildren of the geniuses who proposed these low-cholesterol indictments. How many more generations will be affected by the policies propagating the low-fat hypothesis? Are we de-evolving as a species *hint....WALL*E *?
Thematic review series: Brain Lipids. Cholesterol metabolism in the central nervous system during early development and in the mature animal. Journal of Lipid Research, Vol. 45, 1375-1397, August 2004.

BIOACTIVE LIPIDS -- BEST BALANCE -- BETTER THAN Torcetrapib Fish oil EPA + DHA and seafood naturally lower CETP activity (preventing cholesterol transfer) and power up PLTP (moving phospholipids out of lipoprotein fractions). I had a hard time locating any VAP/NMR data on effects of fish oil components EPA and DHA, but two studies below demonstrate the outcome of EPA and DHA ingestion in depleting phospholipids out of LDL and HDL particles. (1) Small supplements of N-3 fatty acids change serum low density lipoprotein composition by decreasing phospholid and apolipoprotein B concentrations in young adult women. Terpstra AH et al. Eur J Nutr. 1999 Feb;38(1):20-7. (2) The effect of dietary n-3 polyunsaturated fatty acids on HDL cholesterol in Chukot residents vs Muscovites. Astakhova T et al. Lipids. 1991 Apr;26(4):261-5.
Native Chukot Peninsula residents, in contrast to Muscovites, consume a diet rich in n-3 polyunsaturated fatty acids. This dietary peculiarity is reflected in differences in plasma lipid and apolipoprotein contents. The Chukot residents have lower contents of total cholesterol, triglyceride, LDL (low density lipoprotein) cholesterol and apolipoprotein B, but higher HDL (high density lipoprotein) cholesterol levels than do Muscovites. The apolipoprotein A-I levels were identical in both groups. A higher HDL cholesterol to apolipoprotein A-I ratio was determined in the coastline Chukot residents (0.52 +/- 0.01) than in Muscovites (0.43 +/- 0.01; p less than 0.01). In contrast to Muscovites, the coastline Chukot residents also had higher n-3 and lower n-6 polyunsaturated fatty acid percentages in plasma and erythrocyte lipids, and lower phosphatidylcholine and higher sphingomyelin or phosphatidylethanolamine levels in HDL2b and HDL3. The higher HDL cholesterol levels in the plasma of the coastline Chukot residents appears to reflect the higher cholesterol-scavenging capacity of their HDL. We conclude from this

study that the regular consumption of dietary n-3 polyunsaturated fatty acids by the coastline Chukot residents decreased LDL cholesterol transfer from plasma to peripheral cells, and enhanced cholesterol efflux from cellular membranes toward HDL.

A WONDERFUL COMPREHENSIVE REVIEW THAT I *HEART* Nagao K, Yanagita T. Bioactive lipids in metabolic syndrome. Prog Lipid Res. 2008 Mar;47(2):127-46.
"This review explores the physiological functions and molecular actions of bioactive lipids, such as n-3 polyunsaturated fatty acids, conjugated fatty acids, sterols, medium-chain fatty acids (LIKE SATURATED FAT LAURIC, CAPRIC, CAPROIC, CAPRYLIC ACIDS), diacylglycerols and phospholipids, in the development of metabolic syndrome. Dietary bioactive lipids suppress the accumulation of abdominal adipose tissue and lipids in the liver and serum, and alleviate hypertension and type 2 diabetes through the transcriptional regulation of lipid and glucose metabolism. "

[DRUM ROLL...] DIETARY SATURATED FATTY ACIDS ACT LIKE NIACIN Fatty acids including saturated fatty acids also bind PUMA-G and HM74 receptors. This is the receptor family that Niacin binds to and exerts its potent abilities to regress plaque (raise HDL2b 200-300%, lower TGs 40-60%) and evoke its anti-inflammatory effects. See Table 1 full list of the range of ketone body and the saturated fatty acids and their relative receptor affinities. Taggart A, Waters MG et al. (D)-beta-Hydroxybutyrate inhibits adipocyte lipolysis via the nicotinic acid receptor PUMA-G. J Biol Chem. 2005 Jul 22;280(29):26649-52. Full 'accelerated publication' PDF here. Other fatty acids which bind this astounding receptor PUMA-G are in listing of decreasing potency: --Hydroxy-butyrate (ketone bodies associated with exercise training and intermittent fasting) --Lactate (by-product of anaerobic exercise, strength training, intense exercise like CALIfornication) --Acetate (C2), Proprionate (C3) --Decanoate (C10) = caprylic acid, a medium chain saturated fatty acid (MC SFA) --Heptanoic acid (C7) -- Butyrate (C4) = short chain saturated fatty acid from butter oil and produced by gut flora from

ingested fiber like oat bran, pectin, etc --Octanoate (C8) = capric acid, MC SFA --Pentanoic acid (C5) --Hexanoate (C6) = caproic acid, MC SFA --Nicotinic acid (niacin, SLO-NIACIN, NIASPAN) -- binds with high affinity to HM74 mainly

Why do we love lauric acid at the Track Your Plaque forum??? I think Phil and I are currently the biggest fans...

Lauric acid lowers Lp(a)... particularly in men (44%; non-statistically significant). See below Table.

Temme EH, Mensink RP, Hornstra G. Comparison of the effects of diets enriched in lauric, palmitic, or oleic acids on serum lipids and lipoproteins in healthy women and men. Full PDF here. Am J Clin Nutr. 1996 Jun;63(6):897903. PMID: 8644684

Lauric acid also raises HDL -- the plaque regression subfraction (and cancer protective particle). Please see Table 5 -- at the top. In a short six-weeks, lauric acid increased total HDL by: -- 16.7% for men (baseline: HDL = 1.26 mmol/L = 48.7 mg/dl) which appears to correlate well with Lp(a) reduction! Though hard to tell with Lp(a) varying in the deviations and this study population too small for any significance or actual comparisons. -- 5.6% for women (baseline quite higher already than the men and also achieved TYP goals 60-60-60: HDL = 1.58 mmol/L = 61.1 mg/dl; TG=82.3 mg/dl which is pretty close)

In the below research conducted by the same group, they found that "Nevertheless, lipid transfer activities correlated significantly with the relative abundance of HDL2b, HDL2a, HDL3b, and HDL3c with phospholipid transfer activities. In general,

serum phospholipid transfer protein (PLTP) activity correlated positivly with HDL cholesterol after the dietary interventions...serum PLTP activity, as measured as the rate of radiolabeled phosphatidylcholine transferred from liposomes toward serum HDL, was significantly higher with the lauric acid diet (23.5+/2.6%) than with the palmitic acid diet (22.5+/-2.5%) (P = 0.0013)."

Lagrost L, Mensink RP, Guyard-Dangremont V, Temme EH, Desrumaux C, Athias A, Hornstra G, Gambert P. Variations in serum cholesteryl ester transfer and phospholipid transfer activities in healthy women and men consuming diets enriched in lauric, palmitic or oleic acids. Atherosclerosis. 1999 Feb;142(2):395-402.

Food sources rich in lauric acid are:

unrefined coconut oil (40-50%) unrefined palm oil butter oil (greenpastures.com) -- contains also butyrate (ligand for the niacinreceptor), CLA, Vitamin K2, LDL-lowering Plant Sterols, Vitamin A/D/E, omega3 ALA, etc human breastmilk (not my highest recommendation *wink*) (umbellularia californica seeds and flowers... probably other herbal seeds too but haven't had time to verify)

Cardiovascular risk modulators and telomere length reducers:

Vitamin D deficiency (25(OH)D less than 50 ng/ml) Oxidative stress Psychological stress (ie, sleep deprivation) Hypertension Estrogen deficiency Sedentary during leisure time Insulin resistance (ie, NAFLD, cardiac steatosis, metabolic syndrome, PCOS) Type 2 Diabetes Type 1 Diabetes Obesity Homocysteine Smoking (All of the above are modifieable factors in the TrackYourPlaque program)

Fuster JJ, Andrs V. Circ Res. 2006 Nov 24;99(11):1167-80. Telomere biology and cardiovascular disease. Richards JB, Valdes AM, Gardner JP, Paximadas D, Kimura M, Nessa A, Lu X, Surdulescu GL, Swaminathan R, Spector TD, Aviv A. Higher serum vitamin D concentrations are associated with longer leukocyte telomere length in women. Am J Clin Nutr. 2007 Nov;86(5):1420-5. Aviv A. Hypothesis: pulse pressure and human longevity. Hypertension. 2001 Apr;37(4):1060-6.

W. Browner, et al. The genetics of human longevity. The American Journal of Medicine, Volume 117, Issue 11, Pages 851-860. Kenyon C. The plasticity of aging: insights from long-lived mutants. Cell. 2005 Feb 25;120(4):449-60. Njajou OT, Cawthon RM, Damcott CM, Wu SH, Ott S, Garant MJ, Blackburn EH, Mitchell BD, Shuldiner AR, Hsueh WC. Telomere length is paternally inherited and is associated with parental lifespan. Proc Natl Acad Sci U S A. 2007 Jul 17;104(29):12135-9. Haussmann MF, Mauck RA. Telomeres and longevity: testing an evolutionary hypothesis. Mol Biol Evol. 2008 Jan;25(1):220-8. Richards JB, et al. Homocysteine levels and leukocyte telomere length. Atherosclerosis. 2008 Feb 14; [Epub ahead of print] Cherkas LF, et al. The association between physical activity in leisure time and leukocyte telomere length. Arch Intern Med. 2008 Jan 28;168(2):154-8.

The Fructose Index is the New Glycemic Index

I stumbled upon an interesting editorial recently in the American Journal of Clinical Nutrition from Dr. Richard Johnson's group, entitled "How Safe is Fructose for Persons With or Without Diabetes?" It was a response to a meta-analysis in the same journal pronouncing fructose safe up to 90 grams per day. That's the amount in eight apples or four cans of soda. Not quite what our hunter-gatherer ancestors were eating! The editorial outlined the case against excessive fructose, which I feel is quite strong. That led me to another, more comprehensive paper from Dr. Johnson's group, which argues that the amount of fructose found in a food, which they call the "fructose index", is more relevant to health than the food's glycemic index. The glycemic index is a measure of the blood sugar response to a fixed amount of carbohydrate from a particular food. For example, white bread has a high glycemic index because it raises blood sugar more than another food containing the same amount of carbohydrate, say, lentils. Since chronically elevated blood sugar and its natural partner, insulin resistance, are part of the metabolic syndrome, it made sense that the glycemic index would be a good predictor of the metabolic effect of a food. I believed this myself for a long time. My faith in the concept began to erode when I learned more about the diets of healthy traditional cultures. For example, the Kitavans get 69% of their calories from high-glycemic index carbohydrates (mostly starchy root vegetables), with little added fat-- that's a lot of fast-digesting carbohydrate! Overweight, elevated insulin and other symptoms of the metabolic syndrome are essentially nonexistent. Throughout Africa, healthy cultures make dishes from grains or starchy tubers that are soaked, pounded, fermented and then cooked. The result is a pile of mush that is very easily absorbed by the digestive tract, which is exactly the point of going through all the trouble. The more I thought about the glycemic index and its relationship to insulin resistance and the metabolic syndrome, the more I realized there is a disconnect in the logic: elevated post-meal glucose and insulin do not necessarily lead to chronically elevated glucose and insulin. Here's what Dr. Mark Segal from Dr. Johnson's group had to say:

We suggest that the [glycemic index] is better aimed at identifying foods that stimulate insulin secretion rather than foods that stimulate insulin resistance. The underlying concept is based on the principle that it is the ingestion of foods that induce insulin resistance that carries the increased risk for obesity and cardiovascular disease and not eating foods that stimulate insulin secretion. Well said! I decided to take a look through the literature to see if there had been any trials on the relationship between a diet's glycemic index and its ability to cause satiety (fullness) and affect weight. I found a meta-analysis from 2007. Two things are clear from the paper: 1) in the short term, given an equal amount of carbohydrate, a diet with a low glycemic index is more satiating (filling) than one with a high glycemic index, leading to a lower intake of calories. 2) this effect disappears in the long-term, and the three trials (1, 2, 3) lasting 10 weeks or longer found no consistent effect on caloric intake or weight*. As a matter of fact, the only statistically significant (p less than 0.001) weight difference was a greater weight loss in one of the high-glycemic index groups! As I've said many times, the body has mechanisms for maintaining weight and caloric intake where they should be in the long term. As long as those mechanisms are working properly, weight and caloric intake will be appropriate. The big question is, how does the modern lifestyle derail those mechanisms? Dr. Johnson believes fructose is a major contributor. Table sugar, fruit, high-fructose corn syrup and honey are all roughly 50% fructose by calories. Total fructose consumption has increased about 19% in the U.S. since 1970, currently accounting for almost one eighth of our total calorie intake (total sugars account for one quarter!). That's the average, so many people actually consume more. Fructose, but not starch or its component sugar glucose, causes insulin resistance, elevated serum uric acid (think gout and kidney stones), poorer blood glucose control, increased triglycerides and LDL cholesterol in animal studies and controlled human trials. All of these effects relate to the liver, which clearly does not like excessive fructose (or omega-6 oils). Some of these trials were conducted using doses that are near the average U.S. intake. The effect seems to compound over time both in humans and animals. The overweight, the elderly and the physically unfit are particularly vulnerable. I find this pretty damning. Drs. Johnson and Segal recommend limiting fructose to 15-40 grams per day, which is the equivalent of about two apples or one soda (choose the apples!). They also recommend temporarily eliminating fructose for two weeks, to allow the body to recover from the negative long-term metabolic adaptation that can persist even when intake is low. I think this makes good sense. The glycemic index may still be a useful tool for people with poor glucose control, like type II diabetics, but I'm not sure how much it adds to simply restricting carbohydrate. Reducing fructose may be a more effective way to address insulin resistance than eating a low glycemic

index diet. *Here was the author's way of putting it in the abstract: "Because of the increasing number of confounding variables in the available long-term studies, it is not possible to conclude that lowglycaemic diets mediate a health benefit based on body weight regulation. The difficulty of demonstrating the long-term health benefit of a satietogenic food or diet may constitute an obstacle to the recognition of associated claims." In other words, the data not supporting our favorite hypothesis is an obstacle to its recognition. You don't say?

Isn't it fascinating how thyroid hormone and D3 hormone are interrelated. ---When D3 hormone (sunlight) is lacking, thyroid function suffers ---When thyroid hormone is lacking, a high D3 dose fails to increase 25(OH)D much.... ---When thyroid hormone is NOT lacking, high dose D3 causes a large increase in 25(OH)D (in normal euthryoid controls) it all sounds very familiar to me... :)

Vitamin D3 stalls thyroid cancer, one case report:

Endocr J. 2005 Oct;52(5):613-6. Links Vitamin D3 treatment for locally advanced thyroid cancer: a case report.Morishita M, Ohtsuru A, Kumagai A, Namba H, Sato N, Hayashi T, Yamashita S. Department of Molecular Medicine, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Japan. There are many intricacies in the surgical treatment of locally advanced thyroid cancer, including the medical management of the remaining functional organ and any cosmetic impairments, which are sometimes very difficult to manage and eventually carry a relatively high morbidity and mortality. Here, we report on a case of a 65-year-old female with an extremely locally-advanced thyroid cancer involving both lobes of the thyroid, blood vessels, trachea and esophagus. Despite the severity of her condition, oral administration of vitamin D3 (alphacalcido) has stalled both the tumor growth and further increases of serum thyroglobulin (Tg) level, and has led to a good preservation of quality of life for the last two years. Several reports have previously demonstrated the efficacy of vitamin D3 to inhibit the proliferation of thyroid cancer cell lines in vitro, but clinical evidence has been limited so far. Therefore, this case report provides important evidence for the effectiveness of vitamin D3 therapy against advanced thyroid cancers. PMID: 16284441 [PubMed - indexed for MEDLINE]

Fish oil benefits Medical Research News Published: Sunday, 30-Dec-2007 It's good news that we are living longer, but bad news that the longer we live, the better our odds of developing late-onset Alzheimer's disease. Many Alzheimer's researchers have long touted fish oil, by pill or diet, as an accessible and inexpensive "weapon" that may delay or prevent this debilitating disease. Now, UCLA scientists have confirmed that fish oil is indeed a deterrent against Alzheimer's, and they have identified the reasons why. Reporting in the current issue of the Journal of Neuroscience, now online, Greg Cole, professor of medicine and neurology at the David Geffen School of Medicine at UCLA and associate director of UCLA's Alzheimer Disease Research Center, and his colleagues report that the omega-3 fatty acid docosahexaenoic acid (DHA) found in fish oil increases the production of LR11, a protein that is found at reduced levels in Alzheimer's patients and which is known to destroy the protein that forms the "plaques" associated with the disease. The plaques are deposits of a protein called beta amyloid that is thought to be toxic to neurons in the brain, leading to Alzheimer's. Since having high levels of LR11 prevents the toxic plaques from being made, low levels in patients are believed to be a factor in causing the disease. Alzheimer's is a debilitating neurodegenerative disease that causes memory loss, dementia, personality change and ultimately death. The national Alzheimer's Association estimates that 5.1 million Americans are currently afflicted with the disease and predicts that the number may increase to between 11 million and 16 million people by the year 2050. The researchers examined the effects of fish oil, or its component DHA, in multiple biological systems and administered the oil or fatty acid by diet and by adding it directly to neurons grown in the laboratory. "We found that even low doses of DHA increased the levels of LR11 in rat neurons, while dietary DHA increased LR11 in brains of rats or older mice that had been genetically altered to develop Alzheimer's disease," said Cole, who is also associate director of the Geriatric Research Center at the Veterans Affairs Medical Center. To show that the benefits of DHA were not limited to nonhuman animal cells, the researchers also confirmed a direct impact of DHA on human neuronal cells in culture as well. Thus, high levels of DHA leading to abundant LR11 seem to protect

against Alzheimer's, Cole said, while low LR11 levels lead to formation of the amyloid plaques. Fish oil and its key ingredient, omega-3 fatty acids (found in fatty fish like salmon), have been a mainstay of alternative health practitioners for years and have been endorsed by the American Heart Association to reduce the risk of cardiovascular disease. Fatty acids like DHA are considered "essential" fatty acids because the body cannot make them from other sources and must obtain them through diet. Years of research have shown that DHA is the most abundant essential fatty acid in the brain, Cole said, and that it is critical to fetal and infant brain development. Studies have also linked low levels of DHA in the brain to cognitive impairment and have shown that lower levels may increase oxidative stress in the brains of Alzheimer's patients. Based on the positive results, the National Institutes of Health is currently conducting a large-scale clinical trial with DHA in patients with established Alzheimer's disease. For those patients, Cole said, it may be too late in the disease's progression for DHA to have much effect. But he is hopeful that the NIH will conduct a large-scale prevention clinical trial using fish oil at the earliest stages of the disease - particularly because it is unlikely that a pharmaceutical company will do so, since fish oil in pill form is readily available and inexpensive. Still to be determined, he said, "is what the optimal dose should be. It could be that a smaller amount might be helpful, especially in a place like the south of France, where people are already on a Mediterranean diet." Here in the United States, though, where fish consumption is not very high, the dose may need to be higher. "There's a deficiency of DHA to begin with," Cole said, "and this may contribute to the low LR11 seen in many Alzheimer's patients." http://www.ucla.edu/ This is for the person asking about Alzheimer's.

The benefits from dietary fat and protein sourced from grass- and clover-fed cows include hitting my favorite family of metabolic and proliferative switches in the mammalian kingdom... PPAR -- alpha gamma and delta! Not only does

consumpation of dietary protein like beef and whey dairy protein activate mTOR and indirectly PPAR-delta, a natural fatty acid called conjugated linoleic acid (CLA) found only in the meat and milk of pasture-fed cows like the ones in the picture also directly binds PPAR receptors. Like many mysteries and secrets revealed by my MILFy buff girlfriends, CLA grows muscle to be defined, lean, and tight. Body fat significantly decreases and minimizes (but it aint a miracle -- you still need to work a little, ie lift and pump and eat right). What girl (or TYPer) wouldn't want that? Additionally CLA reduces cancer and reduces proliferation. CLA is produced by the bacteria in the bellies of ruminants who consume grass or clover (not hay or grains). Food sources of CLA (and Vits K2, D3, A, Butyric acid, EPA, DHA) : --pasture-fed cowmilk (at most good health food stores: Organic Pastures $6.99/qt) --raw pasture-fed cowmilk (see above --contains 'Wulzen Factor' = heat-labile stigmasterol which is an unsaturated plant sterol which lowers cholesterol) --pasture-fed cowmilk cheese, butter, raw butter oil --pasture-fed goat milk, dairy products Protein sources with CLA (and DHA+EPA/aka 'fish oil'): --pasture-fed beef --pasture-fed lamb --pasture-fed sheep --pasture-fed goat --pasture-fed bison, wild bison --wild deer, elk, antelope

Of course I like CLA because also it potently binds and activates PPAR -- all of them. Alpha, gamma and beta/delta. This is why my muscles feel so wonderful and grow well (after like... some strain and pain... scrubbing those plaquey-toilets at home). CLA raises muscle mass with resistance training in humans and reduces weight in the obese humans (and in rats):

Lowery LM, et al. Conjugated linoleic acid enhances muscle size and strength gains in novice bodybuilders. Med Sci Sports Exerc. 30(5):S182, 1998. Pinkoski C, et al. The effects of conjugated linoleic acid supplementation during resistance training. Med Sci Sports Exerc. 2006 Feb;38(2):339-48. Tarnopolsky MA, Safdar A. The potential benefits of creatine and conjugated linoleic acid as adjuncts to resistance training in older adults. Appl Physiol Nutr Metab. 2008 Feb;33(1):213-27. Review. Blankson H, et al. Conjugated linoleic acid reduces body fat mass in overweight and obese humans. J Nutr. 2000 Dec;130(12):2943-8. Gaullier JM, et al. Six months supplementation with conjugated linoleic acid induces regional-specific fat mass decreases in overweight and obese. Br J Nutr. 2007 Mar;97(3):550-60. Gaullier JM, et al. Supplementation with conjugated linoleic acid for 24 months is well tolerated by and reduces body fat mass in healthy, overweight humans. J Nutr. 2005 Apr;135(4):778-84. Gaullier JM, et al. Conjugated linoleic acid supplementation for 1 y reduces body fat mass in healthy overweight humans. Am J Clin Nutr. 2004 Jun;79(6):1118-25. Risrus U, et al. Conjugated linoleic acid (CLA) reduced abdominal adipose tissue in obese middle-aged men with signs of the metabolic syndrome: a randomised controlled trial. Int J Obes Relat Metab Disord. 2001 Aug;25(8):1129-35. Eyjolfson V, et al. Conjugated linoleic acid improves insulin sensitivity in young, sedentary humans. Med Sci Sports Exerc. 2004 May;36(5):814-20. Liu LF, et al. Combined effects of rosiglitazone and conjugated linoleic acid on adiposity, insulin sensitivity, and hepatic steatosis in high-fat-fed mice. Am J Physiol Gastrointest Liver Physiol. 2007 Jun;292(6):G1671-82. Park Y, et al. Changes in body composition in mice during feeding and withdrawal of conjugated linoleic acid. Lipids. 1999 Mar;34(3):243-8.

Muller et al studied how if human vascular cells also may carry CLA as ruminant tissues do... guess what he found? Mller A, et al. Detection of conjugated dienoic fatty
acids in human vascular smooth muscle cells treated with conjugated linoleic acid. Biochim Biophys Acta. 2005 Dec 15;1737(2-3):145-51.

"Conjugated linoleic acids (CLA) have attracted scientific interest due to their potential beneficial effects on atherosclerosis. Recent studies demonstrated that conjugated metabolites of CLA are found in tissues of CLA-fed animals and cultured cells treated with CLA. This observation has gained in importance since it has recently been shown that these metabolites of CLA exert specific biological activities...Examination of fatty acid composition of total cell lipids ...revealed a significant isomer-specific formation of conjugated metabolites of CLA such as CD16:2, CD20:2 and CD22:2 in human coronary artery smooth muscle cells treated with various CLA isomers. Different CD16:2/CLA ratios between various CLA isomers as observed in the present study indicate that fatty acid metabolism is differently

affected by the configuration of the double bonds. In conclusion, the observation from the present study suggests that the effects of CLA in vascular cells might not only be mediated by CLA itself but also by its conjugated metabolites."

Of course synthetic CLA is artificially created with hydrogenated cheap industrial veggie oils which is not likely to be as beneficial (longterm) as naturally derived CLA from whole foods.

RELATED LINKS:

Higher concentrations of vitamin E, CLA, long change omega-3 fatty acids in pasture fed cow milk. Leiber F, et al. A study on the causes for the elevated n-3 fatty acids in cows' milk of alpine origin. Lipids. 2005 Feb;40(2):191-202. PMID: 15884768

Grain (corn) feeding lowers CLA and content of other important nutrients like Butyric acid (4-carbon fatty acid) in the fat of cow milk. Stockdale CR, et al. Influence of pasture and concentrates in the diet of grazing dairy cows on the fatty acid composition of milk. J Dairy Res. 2003 Aug;70(3):267-76. PMID: 12916820

Beef meat considered a source of 'omega-3s' EPA/DHA when pasture fed. Mann NJ, et al. Feeding regimes affect fatty acid composition in Australian beef cattle. Asia Pac J Clin Nutr. 2003;12 Suppl:S38. PMID: 15023647

Ponnampalam EN, et al. Effect of feeding systems on omega-3 fatty acids, conjugated linoleic acid and trans fatty acids in Australian beef cuts: potential impact on human health. Asia Pac J Clin Nutr. 2006;15(1):21-9. PMID: 16500874

Cardioprotective Effects of Vitamin A

(RA=retinoic acid is the carboxylic acid of vitamin A) (All-trans-retinoic acid (ATRA) is the primary active metabolite of vitamin A) (9-Cis retinoic acid, a metabolite of vitamin A, is the most potent ligand of RXR)

Wu J 1996: Vitamin D3 and retinoic acid protect against hypertrophy of neonatal rat cardiac myocytes induced by endothelin Zhou MD 1995: Retinoid-dependent pathways suppress myocardial cell hypertrophy by minimizing alpha-adrenergic receptor-dependent hypertrophy Kang, Leaf 1995: All-trans-retinoic acid protects against cardiac arrhythmias induced by ischemia, adrenaline-like stimulants de Paiva 2003: Retinoic acid at small physiological doses remodeled damaged heart issue in adult rats Wang 2003: All-trans-retinoic acid prevented remodeling in cultured rat cells and cardiac hypertrophy induced by angiotensin II Worley JR 2003: 9-cis-retinoic acid prevent MMP-9 in human monocyte-like cells de Paiva 2005: Retinoic acid supplementation attenuates ventricular modeling postmyocardial infarction in rats Preston 2005: All-trans retinoic acid elicits inhibition of serontonin-induced changes in cultured human smooth muscle cells (took cells from human subjects with idiopathic pulmonary arterial hypertension who often demonstrate low serum levels of RA and 13-cis-RA compared with healthy controls) Choudray 2007: All-trans-retinoic acid in pressure overloaded rats (by aortic band) prevented systolic and diastolic dysfunction and change in cardiac structure by inhibiting the rennin-angiotensin system. Choudray 2008: All-trans-retinoic acid prevents angiotensin II and mechanical stretch induced ROS generation cardiomyocyte cell death Mercader 2006: with retinoic acid remodeling of WAT in mice, increased thermogenesis in skeletal muscle, triggered reduction in body weight, reduction in visceral fat, improved glucose tolerance

Luminations: Coronary Luminology, Lipids, Laughs

Nakashima et al admit that "Despite the fact that millions of dollars have been spent over the last 50 years on atherosclerosis research, little is known about the development of early human atherosclerosis. There are several reasons why the research on early human atherosclerosis has not advanced. First, human atherosclerosis develops very slowly and at different rates from individual to individual, and it is difficult to distinguish between lesion initiation and progression. Second, a thickened intima is present in human arteries before atherosclerosis develops, but whether this intima forms the precursor for the later more advanced lesion is not fully understood. Third, the relationship between extracellular lipids and macrophages has not been clarified (UUUMMM... yeah hyper-reduction of human cholesterol may indeed lead to cancer -- see the SEAS trial... or J-Litt or IMPROVE-IT or hey...very SHARP mono-statinators...). It is generally believed that extracellular lipids are derived from foam cell death, but there are several examples that show that extracellular lipid occurs independently of macrophage cell death. Finally, there are no good animal models for the study of early atherogenesis. The

morphological features of early atherosclerosis are different between humans and laboratory animal models, and it may be somewhat misleading to extrapolate the results obtained from animal models, to humans." (though rabbits are very cute and so are indeed are we, we aren't evolved exactly like herbivores) Thus...more Animal Pharm facts!

What we are certain of though is that HDL2 -- the large puffy HDLs -- are strongly associated with plaque regression, centenarian-lives/longevity, and cancer reduction (Michalaki et al Mol Cell Biochem. 2005 Jan;268(1-2):19-24). How can we achieve higher HDL2, these wonderfully big ghetto-fab puff-daddies? Cholesterol Intake on HDL2 and Reduction of Small Dense LDL Olson et al researchers examined the effects of (!!)Cholesterol and (!!)Saturated fats on HDL2 (good) and HDL3 (bad) particle sizes. Schonfeld G, Patsch W, Rudel LL, Nelson C, Epstein M, Olson RE.
Effects of dietary cholesterol and fatty acids on plasma lipoproteins. J Clin Invest. 1982 May;69(5):1072-80. PMID: 7068846

ABSTRACT..... The effects of dietary cholesterol and fatty acids on low density and high density lipoproteins (LDL and HDL) were studied in 20 young men. After 2-3 wk of evaluations on ad lib. diets (Latin for eating without controls), basal diets, which consisted of 15% protein, 45% carbohydrates, 40% fat, and 300 mg/day of cholesterol, were given for 4-5 wk (Basal). The ratio of dietary polyunsaturated to saturated fatty acids (P/S) for different groups of subjects were 0.25, 0.4, 0.8, or 2.5. 750 and 1,500 mg/d of cholesterol were added to the basal diets as 3 and 6 eggs, respectively. RESULTS Total cholesterol and LDL cholesterol (READ: MORE SMALL DENSE LDL -'BAD') were lower in all subjects on the basal diets than on the ad lib. diets... Thus, both the cholesterol contents and P/S ratios of diets were important in determining LDL levels... On the diet with low P/S ratio (this means lowest PUFA proportion, highest S-A-T-UR-A-T-E-D FATS), HDL2 rose (good), whereas this effect was absent on diets with high P/S ratios. CONCLUSION The response of LDL to dietary manipulations is consonant with epidemiologic data relating diets high in cholesterol and saturated fat to atherogenesis (NO... NOT TRUE. Mono-statinators rot...substitute the words 'carbohydrates' and 'carbohydrates' respectively...cholesterol does not kill...

Carbs/whole-grains do). The response of HDL2, however, is opposite to that of its putative role as a negative risk factor. Further work is needed to clarify this interesting paradox (THE EDITORS LIKELY MADE THE AUTHORS PUT THIS IN... TRANSLATION, WE'RE COMPLETELY BEFUDDLED BY THESE RESULTS). Highest Sat Fats and Cholesterol Promote HDL2 Concordant with Regression In addition to showing the HIGHEST INCREASE in HDL2 and the DEEPEST DROP in HDL3, Olson et al also discovered that the highest sat-fat ratios (4:1) produced the LOWEST apo B, HIGHEST apoA-I/apoA-II and LIGHTEST FLUFFIEST LDL-CHOL (see table III, IV, V). WOW. All good things. Sounds regressive to me. Quite (accidentally) awesome for these scientists from Washington and St Louis Med Schools out in Misery. Dr. Olson also authored a quite profoundly articulate paper entitled "Is it wise to restrict fat in the diets of children?" a few years after the above sat-fat discoveries. Brave scientist. Differences Between Moderate vs. High Cholesterol Intake Did the authors find a clinical difference between Cholesterol intake of 750 mg/day vs. 1500 mg/day? Of course! 1500mg per day (6 eggs) of cholesterol yielded lower apo B (bad) (102 mg/dl vs. 92 mg/dl) and VLDL (very bad stuff)(68 mg/dl vs. 48 mg/dl). The best total HDLs for any of the subgroups studied was: highest sat fats and highest cholesterol 1500mg/day -- 52 mg/dl vs. 50 mg/dl (3 eggs/750mg/d). Without a doubt, the most optimal HDL2/HDL3 ratio was achieved with the highest sat fat ratio and the highest cholesterol intake 1500mg/d 6 eggs daily (see Table). So... How do we achieve higher HDL2? Like a little piggy, I'm laughing all the way to the market to buy cholesterol/eggs *grin* If we take lessons learned from these 20 young men...If our diet consists of 40% fats and our caloric intake is ~2000 cal/day -- fats could comprise approximately (0.40 x 2000) = 800 cal/day. Fats are 9 cal/g -- this amount is equivalent to about 88 grams fat total. (Protein 15% 75 grams; Carbs 45% 225 grams OMG -- too much carbs)

A portion of the fat would be MUFA (monounsaturated) and small amounts PUFA (olive oil, fish oil, GLA, chocolate, nuts, nut butters, veggies, etc) and a certain ratio of saturated fats. Add also the cholesterol equivalent of 6 eggs = 1500 mg cholesterol daily. One Tablespoon of Fat contains approx 13-15 grams fat. SATURATED SFA include butter, butter oil, ghee, virgin coconut oil, MCTs, lard, egg yolks, grass-fed meat, seafood, fish, mollusks, etc. (using omega-3 eggs adds in lutein 8x more per egg and fabulous DHA!) One large AA omega-3 egg contains about 4.5 grams fat of which 1.5 grams saturated Individual Genetic Variations The Missouri authors did point out that increases in LDL varied significantly among the male subjects. Like responses to Lp(a) reduction, it appears genetics and dietgene interaction may play a large part. In the above trial, carb intake was extremely high and as we aware carbs modulate apo B and sdLDL (and HDL2). The meat used in the trial were from a 'local meat processor' in Missouri. Perhaps back then in the 1980s, the EPA + DHA content was already depleted from common meat sources. Many factors (high carbs high carbs high carbs, no EPA DHA, Cholesterol insufficiency) exist that may explain how the baseline HDLs of these young healthy robust mid-western study participants was only in the mid-40s. Curiously, apo E polymorphisms and other genetic influences (like PPAR-d a g) may be major players for the optimum diet for regression and fat intake. Pang et al studied apo E patterns in Hong Kong and noticed that carriers of E2 had the best highest apo E levels compared with homozygous apo E3. Other observations were that "Apolipoprotein E (apo E) allele frequencies were: epsilon2 8.7%, epsilon3 80.4% and epsilon4 10.9% with the genotype having a significant effect on plasma apo E concentration (p less than 0.001). Lipoprotein(a) levels were higher in women than men (geometric mean 15.2 versus 10.2 mg/dL, p less than 0.05) and in women with FSH above versus below 40 IU/L (185 versus 136 mg/L, p less than 0.05)." It's not clear to me yet how to discern our apo E polymorphisms without genetic testing and what is the precise diet-gene interaction because optimally the studies would consider the effects of a no-grains/Paleo diet, and unfortunately few take this stance in the medical literature.

Eggs on the other hand appear great! Perhaps the fox know best...

Effect of egg yolk feeding on the concentration and composition of serum lipoproteins in man. Beynen AC, Katan MB. Atherosclerosis. 1985 Feb;54(2):157-66.

The effect of egg yolk consumption on the composition of LDL and on the concentration of HDL subclasses was studied in healthy subjects. Six volunteers consumed a diet low in cholesterol for 10 days and then daily added 6 egg yolks to their diet for another 10 days; the experiment was repeated 1 year later with the same subjects. Egg yolk consumption caused the cholesterol intake to increase by 1600 mg/day, and the fat intake by 7 energy % at the expense of carbohydrates; this increase was due almost exclusively to monounsaturated fatty acids. RESULTS: Upon egg yolk feeding the mean level of serum total cholesterol rose by 13%; the bulk of this rise was due to LDL cholesterol, which increased by 21% (READ: REDUCTION IN sdLDL). VLDL and IDL cholesterol decreased by 19 and 11% (good), and serum total triglycerides by 17% (great). Marked relative increases of 35 (very good) and 36% (very very good) were seen in the cholesterol level of the HDL subfractions with densities of 1.0551.075 g/ml (HDL1) and 1.075-1.100 g/ml (HDL2), respectively. The HDL2/LDL cholesterol ratio increased by 16% (VERY VERY GOOD). No change in cholesterol in HDL3 (d greater than 1.100 g/ml) was observed (GOOD!). The increase in cholesterol in HDL isolated by density gradient ultracentrifugation significantly exceeded the increase in cholesterol in heparin-Mn2+ soluble HDL. This suggests the formation of apo E-containing HDL, i.e. HDLc, which has HDL density but is not soluble in heparin-Mn2+. (? translation please?...Is Krauss in the house?) The composition of the LDL particles was significantly altered; the core became enriched in esterified cholesterol at the expense of triglycerides, and the ratio of core components to surface components increased by 7%. (read again: elimination of sdLDL and rise in round, puffy fluffy LDL particles *cheers!*) PMID: 3986015

The Leaky Gut

The Gastro-intestinal (GI) tract is the main frontier between us and the environment. It is where nutrition, water, minerals become absorbed to sustain life. However, it also serves as a barrier against ingested toxins like pathogenic bacteria and viruses. In fact 70% of the lymphatic tissue in the body is associated with the GI tract. This system is referred as the Gut Associated Lymphoid Tissue (GALT).

In order to function properly, the GI tract must be able absorb the appropriate materials the body requires while shielding harmful toxins. The intestines contain numerous finger like microscopic projections called villi. The purpose of the villi is to absorb the needed elements. Furthermore, their finger like projections also allow for increased surface area for a larger absorptive capacity.

At a closer view, the epithelial cells of the villi are joined together by proteins called Tight Junctions. These junctions serve as a selective barrier between the cells. Moreover, the tight junctions are comprised of several types of proteins and their supportive scaffolding. 90% of the matter that is absorbed into the body comes through the cells themselves. This process is referred as a transcellular pathway. The other 10% is absorbed between the cells called the paracellular pathway. Disease occurs when the tight junctions become "leaky" allowing pathogens to enter by the paracellular pathway. When this occurs, the GALT immune system will become activated. However, during this stimulation, the GALT system may produce antibodies which cross react with native proteins. Thus, autoimmune diseases may occur like Type I Diabetes Mellitus which is an autoimmune disease against the beta cells of the pancreas. This leads to decreased insulin production by the pancreas. Type II Diabetes Mellitus is due to insulin resistance.

Vitamin D

Vitamin D had been related to the class of Inflammatory Bowel Diseases (IBD) such as Crohn's Disease and Ulcerative Colitis. Symptoms of IBD can be diarrhea, GI bleeding, kidney stones, arthritis, weight loss, and others. A study in the American Journal of Gastroenterology, Oct, 2008 showed: " in both Crohn's disease (CD) and ulcerative colitis (UC) patients, vitamin D deficiency was independently associated with having increased disease activity scores compared to those with normal levels of Vitamin D. Vitamin D deficient CD patients, but not UC patients, had worse quality of life when compared to patients who were not Vitamin D deficient." I found a very interesting article by Juan Kong, et al, 2008 regarding the leaky gut

and Vitamin D (1). The researchers looked at the role of the Vitamin D Receptor (VDR) in the intestines of mice with and without the expression of VDR receptors. What they found was that mice without VDR expression in their intestines:

had impaired cellular healing whereas Vitamin D supplementation increased cellular migration for the healing process the Tight Junctions (TJ) were more susceptible to damage whereas Vitamin D supplementation increased the expression of TJ proteins VDR lacking mice lost more weight and developed more symptoms like GI bleeding and dehydration than VDR + mice, just like IBD patients.

Thus Vitamin D is important for Tight Junction strengthening and cellular healing in the intestines. This may be one mechanism of how Vitamin D supplementation (sunlight or softgels) decreases the risk of autoimmune diseases.

Type I Diabetes Mellitus (Type I DM) Type I DM is, an autoimmune disease, is now being linked to the GI system as a possible origin to the disease. Recent studies cite the protein Zonulin as an inciting factor for Type I DM. (2,3) Zonulin is an enzyme that increases intestinal permeability by breaking down the Tight Junction structure. One study showed that in Type I Diabetics, 41% had abnormally high Zonulin levels compared to controls. (2) Moreover, testing in the pre-diabetic phase (3.5 +/- 0.9 years prior to the onset of Type I DM), showed elevated zonulin levels that were detected in 70% of the patients.

Celiac Disease Celiac Disease is the autoimmune disease of the GI system due to gluten sensitivity. Gluten is the protein found in wheat. Gliadin is the inciting element which is the alcohol soluble fraction of gluten. (4) In addition, Gliadin stimulates the immune system which then produces inflammatory chemicals called cytokines like TNFalpha and Interleukins. Celiac disease leads to the symptoms of abdominal bloating and diarrhea. However, iron deficiency is now the most common clinical presentation. (5) And 50% of the patients do not have significant diarrhea. (5) The disease is estimated to be 1% of the population. (6) However, this may be grossly underestimated as screening is not commonly performed and is not 100% sensitive.

Celiac disease can cause folate deficiency (causing anemia), Vitamin K deficiency (causing bleeding), and Vitamin D deficiency (leading to bone disease). (5) The occurs due to the fact that the villi of the intestine are eroded leading to decreased ability of absorption. Congestive Heart Failure At rest, the GI system is the most heavily perfused organ in the body. Moreover, a GI tract that is not appropriately perfused with oxygen (blood), may lead to a leaky gut. An intestinal system that is more permeable may allow more toxins like bacteria or bacterial particles into the systemic circulation. Gram negative bacteria contain an endotoxin called lipopolysaccharide (LPS). The LPS of E coli has been associated with Crohn's Disease. (12) Invasive E coli can disrupt the Tight Junction proteins and increase production of inflammatory cytokines. Both of which lead to increased intestinal permeability. One study showed examined patients with congestive heart failure and their correlation with LPS levels and the TNF-alpha.(6) The patients with peripheral edema had higher LPS and TNF-alpha levels which were normalized with intensive diuretic therapy. Thus, poor cardiac output and bowel edema will lead to decreased GI perfusion and increased intestinal permeability. This process allows more toxins to bypass the cellular tight junctions like LPS.

Excessive Exercise Brocke-Utne, et al did a study on 89 randomly selected exhausted runners who required admission to the medical tent for treatment in the 1986 Comrades Marathon. (7) They found that 81% had endotoxin levels above the toxic level of 0.1 ng/ml. "Those runners completing the race in less than 8 hours had a significantly lower average endotoxin value than those taking longer than 8 hours." Patients with CHF can develop bowel ischemia during exercise. (11) Non-steroidal Anti-inflammatory Drugs (NSAIDs) NSAIDs like ibuprofen can cause damage on the GI tract by decreasing prostaglandin production. They also increase intestinal permeability. An article this month reveals "the prevalence of NSAIDs-induced small intestinal injury is higher than had been expected. Recent studies show that more than 50% of patients taking NSAIDs have some mucosal damage in the small intestine." (8) Furthermore, NSAIDs increase intestinal permeability to a greater extent than controls in patients with Inflammatory Bowel Disease. (9) Both NSAIDs and aspirin increase GI permeability during prolonged exercise. (10)

Summary In summary, the GI tract is a selective barrier towards the environment by absorbing nutrients and shielding the body of toxins. However, a increase in intestinal permeability (through the paracellular pathway) by gluten, heart failure, excessive NSAID use, and other toxins can increase the risk of disease. One study in mice reveals that Vitamin D can strengthen the tight junctions and possibily lower the risk of morbidity. It is my feeling that the future of medicine will see the gut, diet, and the silent crisis of Vitamin D deficieny as a central focus on disease prevention and treatment. As seen in my previous post, there is a linkage of Celiac Disease to Schizophrenia. Other associations of Celiac Disease are as follows below:

Definite associations with Celiac Disease (wheat sensitivity) are (5)

Dermatitis herpetiformis IgA deficiency Type 1 diabetes Autoimmune thyroid disease Sjgrens syndrome Microscopic colitis Rheumatoid arthritis Downs syndrome IgA nephropathy

Possibile associations are: (5)

Congenital heart disease Recurrent pericarditis Sarcoidosis Cystic fibrosis Fibrosing alveolitis Lung cavities Pulmonary hemosiderosis Inflammatory bowel disease Autoimmune hepatitis Primary biliary cirrhosis Addisons disease Systemic lupus erythematosus Vasculitis Polymyositis Myasthenia gravis Schizophrenia

1) Kong J, Zhang Z, Musch MW, Ning G, Sun J, Hart J, Bissonnette M, Li YC: Novel role of the vitamin D receptor in maintaining the integrity of the intestinal mucosal barrier.

Am J Physiol Gastrointest Liver Physiol. 2008 Jan;294(1):G208-16 2) Sapone A, de Magistris L, Pietzak M, Clemente MG, Tripathi A, Cucca F, Lampis R, Kryszak D, Carten M, Generoso M, Iafusco D, Prisco F, Laghi F, Riegler G, Carratu R, Counts D, Fasano A: Zonulin upregulation is associated with increased gut permeability in subjects with type 1 diabetes and their relatives. Diabetes. 2006 May;55(5):1443-9. 3) Sapone A, de Magistris L, Pietzak M, Clemente MG, Tripathi A, Cucca F, Lampis R, Kryszak D, Carten M, Generoso M, Iafusco D, Prisco F, Laghi F, Riegler G, Carratu R, Counts D, Fasano A:Zonulin upregulation is associated with increased gut permeability in subjects with type 1 diabetes and their relatives. Diabetes. 2006 May;55(5):1443-9. 4) Green PHR, Cellier C: Celiac Disease. N Engl J Med 357:1731, October 25, 2007 5) Farrell, RJ, Kelly, CP: Celiac Sprue. N Engl J Med, Vol. 346, No. 3. January 17, 2002 6) Krack A, Sharma R, Figulla HR, Anker SD: The importance of the gastrointestinal system in the pathogenesis of heart failure. Eur Heart J. 2005 Nov;26(22):2368-74. 7) Brock-Utne JG, Gaffin SL, Wells MT, Gathiram P, Sohar E, James MF, Morrell DF, Norman RJ: Endotoxaemia in exhausted runners after a long-distance race. S Afr Med J. 1988 May 7;73(9):533-6. 8) Higuchi K, Umegaki E, Watanabe T, Yoda Y, Morita E, Murano M, Tokioka S, Arakawa T: Present status and strategy of NSAIDs-induced small bowel injury. J Gastroenterol. 2009 Jul 1. 9) Kerckhoffs AP, Akkermans LM, de Smet MB, Besselink MG, Hietbrink F, Bartelink IH, Busschers WB, Samsom M, Renooij W: Intestinal Permeability in Irritable Bowel Syndrome Patients: Effects of NSAIDs 10) Lambert GP, Boylan M, Laventure JP, Bull A, Lanspa S: Effect of aspirin and ibuprofen on GI permeability during exercise.Int J Sports Med. 2007 Sep;28(9):722-6. Epub 2007 Apr 13 Dig Dis Sci. 2009 Mar 3. 11) Krack A, Richartz BM, Gastmann A, Greim K, Lotze U, Anker SD, Figulla HR: Studies on intragastric PCO2 at rest and during exercise as a marker of intestinal perfusion in patients with chronic heart failure. Eur J Heart Fail. 2004 Jun;6(4):403-7 12) Maiko Sasaki,et al: Invasive Escherichia coli are a feature of Crohns disease. Laboratory Investigation (2007) 87, 10421054

Dr. Davis pokes fun at the concept of a Wheat Deficiency Syndrome:

Flat abdomenRapid weight loss High energy less mood swings Better sleep Diminished appetite Reduced blood sugar Reduced blood pressure Reduced small LDL and total LDL Increased HDL Reduced triglycerides Reduced C-reactive protein and other inflammatory measures

" So if you want to feel better, rid your body of the "Healthy Grains" that we are being brain washed with that are so good for us. This means foregoing the pastas, cereals, baked goods, breads, crackers, etc.