Medical Hypotheses (2004) 62, 871875

http://intl.elsevierhealth.com/journals/mehy

Nutrition, evolution and thyroid hormone levels a link to iodine deciency disorders?
Wolfgang Kopp*
Diagnostikzentrum Graz, Mariatrosterstrasse 41, 8043 Graz, Austria
Received 17 February 2004; accepted 23 February 2004

Summary An increased iodine requirement as a result of signicant changes in human nutrition rather than a decreased environmental iodine supply is suggested to represent the main cause of the iodine deciency disorders (IDD). The pathomechanism proposed is based on the fact that serum concentrations of thyroid hormones, especially of trijodothyronine (T3), are dependent on the amount of dietary carbohydrate. High-carbohydrate diets are associated with signicantly higher serum T3 concentrations, compared with very low-carbohydrate diets. While our Paleolithic ancestors subsisted on a very low carbohydrate/high protein diet, the agricultural revolution about 10,000 years ago brought about a signicant increase in dietary carbohydrate. These nutritional changes have increased T3 levels signicantly. Higher T3 levels are associated with an enhanced T3 production and an increased iodine requirement. The higher iodine requirement exceeds the availability of iodine from environmental sources in many regions of the world, resulting in the development of IDD. c 2004 Elsevier Ltd. All rights reserved.

Introduction
Iodine deciency disorders (IDD) is a term used to denote all the effects of iodine deciency on growth and development. It is widely held that a decient dietary intake of iodine substrate represents the main cause of IDD: an inadequate iodine supply precludes the synthesis of sufcient amounts of thyroid hormone [1]. Other factors that may play a role in the development of IDD are goitrogens, such as certain vegetable foodstuffs, trace elements, bacterial and chemical water pollutants and genetic factors [2]. A deciency of the soil is thought to cause the decient iodine supply. It has been suggested that
*

a depletion of the soil has arisen from the distant past through glaciation, compounded by the leaching effect of snow, water, and heavy rainfall, which removes iodine from the soil. This deciency of the soil is thought to lead to iodine deciency in all forms of plant life and cereal grown in the soil [1]. But apart from a low iodine intake, there may be another, more important factor responsible for the problem: an increased iodine requirement due to signicant changes in human nutrition during the last 10,000 years. There is some evidence in favour of this assumption: Serum levels of thyroid hormones, especially of trijodothyronine (T3), are dietary dependent, or more precisely, they are dependent on the amount of dietary carbohydrate.

Fax: +43316466925. E-mail address: wk@dzg.at.

0306-9877/$ - see front matter c 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.mehy.2004.02.033

872 A high-carbohydrate nutrition is associated with signicantly higher levels of T3, compared with very low-carbohydrate diets. Our Palaeolithic ancestors subsisted on a very low-carbohydrate/high-protein diet during a long period of human evolution, a diet that is associated with signicantly lower T3 levels. Beginning with the agricultural revolution about 10,000 years ago, a dramatic increase in dietary carbohydrate has occurred. The addition of considerable amounts of carbohydrate to a low-carbohydrate diet is associated with a signicant increase in T3 concentrations. Increased T3 concentrations are associated with a higher iodine requirement, that in many regions of the world exceeds the availability of sufcient amounts of iodine from environmental sources.

Kopp til refeeding [9]. In a study by Barrow and Snook [10], an amount of 30 g of carbohydrate in a calorie-reduced mixed diet was associated with T3 concentrations 36% below base line. T3 levels remained depressed throughout diet (12.922.4 weeks, with a mean of 18.1 weeks). Thus, diets containing no carbohydrate, like for instance diets consisting of fat only [4,5], protein only [5], or protein and fat [4], or diets with a very low carbohydrate content [3,911], are associated with T3 levels up to 50% lower than that associated with a mixed or high-carbohydrate diet. Decreased T3 levels were shown to remain unchanged during the duration of carbohydrate restriction (between 4 days and several months) [4,5,911]. The sharp decline in T3 levels as a result of very low carbohydrate diets is not associated with a reduction in the resting oxygen uptake, or symptoms of functional hypothyroidism (cold intolerance, dry skin, increased need for sleep). Despite decreased T3 concentrations, basal TSH levels are normal or even mildly decreased [4,5,9]. The lack of clinical symptoms, together with normal or mildly decreased TSH levels suggest that the organism does not suffer from a deprivation in thyroid hormone in association with carbohydrate restriction [9,12]. The reasons for these alterations in thyroid hormone levels due to carbohydrate restriction are not completely cleared up. It seems that the lowered T3 levels result from a diminished peripheral conversion of T4 to T3: while under normal conditions, a sizeable fraction of T4, perhaps as much as 3040%, is converted to T3 peripherally, in starvation and carbohydrate restriction, there is a shift in the conversion of T4 from T3 to rT3. Since reverse T3 does not have any signicant hormonal action, this results in a net decrease in hormonal activity [7,12]. In reverse, T3 formation is enhanced when a certain amount of carbohydrate is added to a low-carbohydrate diet, indicating that the metabolization of dietary carbohydrate is a thyroid hormone consuming process. What is the physiological signicance of these diet-induced alterations in thyroid hormone metabolism? There can be no doubt that it is dependent on the starting point we choose to look at things: starting out from a high-carbohydrate nutrition, a reduction of T3 concentrations to approximately 50% as a result of a carbohydrate restriction is astonishing, but since this decrease is not associated with signs of hypothyroidism, the clinical relevance is questionable. A look at the phenomenon from the other end yields a different picture: a very low-carbohydrate

Thyroid hormone levels and nutrition

It is well established that serum levels of thyroid hormones are dietary dependent. Several studies have shown that under isocaloric conditions, variations of diet composition can drastically alter peripheral thyroid hormone metabolism [37]. This has been demonstrated rst in studies on starvation: under total fasting conditions, serum T3 starts to decline within 24 h to reach a plateau approximately 50% below control levels within about 46 days, while reverse T3 (rT3) levels increase and thyroxin (T4) shows little or no effect [3,59]. Further studies proved that this decline in serum T3 is not due to starvation, but results from a reduction in dietary carbohydrate: an isocaloric substitution of fat and/or protein for carbohydrate in a mixed diet was shown to decrease serum T3 concentrations similar to those induced by fasting [4,5,8]. While refeeding (after starvation) with fat and/ or protein has no signicant effect on decreased T3 levels [3,5,8], refeeding with carbohydrate leads to increasing T3 concentrations. The magnitude of this increase is dependent on the amount of carbohydrate, with 50 g of glucose partially [6] and about 160 g of glucose fully restoring T3 to control levels [5,7,8]. Very low carbohydrate diets are associated with signicantly lower T3 concentrations. In an normocaloric diet containing less than 20 g of carbohydrate, T3 concentrations declined and reached a plateau approximately 50% below control levels, and stayed unchanged during a 4 week period un-

Nutrition, evolution and thyroid hormone levels diet is associated with, from this point of view, normal serum thyroid and TSH levels. The addition of signicant amounts of carbohydrate to this diet leads to a signicant increase in serum T3 and a decrease in rT3 levels. These alterations in hormone metabolism are associated with an enhanced thyroid hormone production and, accordingly, with an increasing iodine requirement. Exactly, this may have occurred 10,000 years ago with the onset of agriculture, when our ancestors replaced their high-protein/low-carbohydrate diet with a diet containing increasing amounts of carbohydrate and decreasing amounts of protein.

873 decreased TSH levels becomes quite understandable: these are levels associated with a diet, our ancestors had genetically adapted to during a very long period of human evolution. Thus, these levels must be regarded as normal from an evolutionary point of view.

Agriculture signicant changes in human nutrition and in thyroid hormone levels

Beginning about 10,000 years ago agriculture began to develop. The agricultural revolution brought a sharp increase in the consumption of plant food, particularly of cereals which were high in starch. The industrial revolution, and especially the development of high-speed steel roller mills in the 19th century offered the possibility to grind cereals very nely, thereby removing almost all of the brous indigestible material, and increasing the yield and palatability. At the same time, potatoes and rened sugar were introduced into western diets [1318]. Since the end of 19th century, the consumption of sugar has increased steadily and has now reached 70 kg/150 lb per capita/per year in most western countries [19]. Thus, the carbohydrate content of human nutrition has increased during the millennia, with the current high-carbohydrate nutrition representing the culmination of dietary changes. There can be no doubt that these increasing amounts of dietary carbohydrate must have signicantly altered serum T3 levels during the past 10,000 years. From an evolutionary point of view, serum T3 levels may have increased by a factor of 1.5 since the introduction of starchy foods and of sugar into human nutrition.

Palaeolithic nutrition and thyroid hormone levels

Signicant changes in human nutrition have occurred during human evolution. While in our primate ancestors, carbohydrates in the form of fruits and berries were an important part of their diet, the diet of bipedal hominids became increasingly carnivorous. Early hominids like the Australopithecines, who lived between 3 and 4 million years ago as well as Homo habilis, who appeared about 2.5 million years ago, were scavengers. They subsisted on a mixed diet, consisting of vegetable materials as well as meat from carcasses that were left by true predators. Homo erectus, who appeared about 1.5 million years ago and Homo sapiens who appeared about 500,000 years ago were hunters, who consumed large amounts of meat, and some amounts of carbohydrate in the forms of roots, fruits, tubers, nuts, grains and seeds. Especially during the ice ages when large parts of the world had little vegetation, our ancestors lived on an abundance of animal protein and only minimal amounts of carbohydrates. Most of the wild plants such as roots, berries, nuts, tubers, and leafy vegetables were brous and contained small amounts of glucose only. The amount of carbohydrate eaten may have been as little as 10 g a day, especially during the ice ages [1318]. Thus, during a very long period of human evolution, our ancestors subsisted on a diet high in protein and very low in carbohydrate. In consideration of the relation between dietary carbohydrate and thyroid hormone concentrations, this Palaeolithic nutrition must have been associated with T3 levels signicantly lower than those associated with later high-carbohydrate diets. In this context, the seemingly inappropriate association of low T3 values and normal or even

A link to IDD?
While other factors may play an additional role, iodine deciency undoubtedly is the main cause of IDD. In many regions of the world, the environmental iodine supply is not sufcient to meet the iodine requirement in humans. What is the reason for this imbalance between iodine requirement and iodine supply? Is it really a depletion of the soil as a result of glaciation, as has been proposed? Granted that a depletion of the soil has occurred during the ice ages, this must have been a very slow and long-lasting process. There can be no doubt that a period of several 100,000

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Kopp Other potential consequences of these alterations in thyroid hormone levels should be subject of future investigations.

References
[1] De Groot LJ, Larsen PR, Hennemann G. The thyroid and its diseases. 6th ed. Churchill Livingstone Inc.; 1996. p. 71144. [2] Thilly CH, Vanderpas JB, Bebe N, Ntambue K, Contempre B, Swennen B, et al. Iodine deciency, other trace elements and goitrogenic factors in the etiopathogeny of iodine deciency disorders (IDD). Biol Trace Elem Res 1992;32:22943. [3] Danforth Jr E, Horton ES, OConnell M, Burger AG, Ingbar SH, Braverman L, et al. Dietary-induced alterations in thyroid hormone metabolism during overnutrition. J Clin Invest 1979;64:133647. [4] Otten KJ, Henneman G, Docter R, Visser TJ. The role of dietary fat in peripheral thyroid hormone metabolism. Metabolism 1980;29:9305. [5] Azizi F. Effect of dietary composition on fasting-induced changes in serum thyroid hormones and thyrotropin. Metabolism 1977;27:93542. [6] Burman KD, Diamond RC, Harvey GS, OBrien JT, Georges LT, Bruton J, et al. Glucose modulation of alterations in serum jodothyronine concentrations induced by fasting. Metabolism 1979;28:2919. [7] Spaulding SW, Chopra IJ, Sherwin RS, Lyall SS. Effect of caloric restriction and dietary composition on serum T3 and reverse T3 in man. J Clin Endocrinol Metab 1976;42:197200. [8] Serog P, Apfelbaum M, Autissier N, Baigts F, Brigant L, Ktorza A. Effects of slimming and composition of diets on VO2 and thyroid hormones in healthy subjects. Am J Clin Nutr 1982;35:2435. [9] Phinney SD, Bistrian BR, Wolfe RR, Blackburn GL. The human metabolic response to chronic ketosis without caloric restriction: physical and biochemical adaptation. Metabolism 1983;32:75768. [10] Barrows K, Snook JT. Effect of a high-protein, very-lowcalorie diet on resting metabolism, thyroid hormones, and energy expenditure of obese middle-aged women. Am J Clin Nutr 1987;45:3918. [11] Matzen LE, Kvetny J. The inuence of caloric deprivation and food composition on TSH, thyroid hormones and nuclear binding of T3 in mononuclear blood cells in obese women. Metabolism 1989;38:55561. [12] Kohler PO. Endocrinology and metabolism. In: Stein JH, editor. Internal medicine. Boston: Little, Brown and Company; 1983. p. 1755. [13] Garn SM. What did our ancestors eat? Nutr Rev 1989;47:33745. [14] Sponheimer M, Lee-Thorp JA. Isotopic evidence for the diet of an early hominid, Australopithecus africanus. Science 1999;283:36870. [15] Lee RB, Vore I. Man the hunter. Chicago: Aldie; 1968. [16] Eaton SB, Konner M. Paleolithic nutrition. A consideration of its nature and current implications. New Engl J Med 1985;312:2839. [17] Gaulin SJC, Konner M. On the natural diet of primates, including humans. In: Wurtman RJ, Wurtman JJ, editors. Nutrition of the brain, vol. 1. New York: Raven Press; 1977. p. 18.

Figure 1 Graphic description of the pathomechanism proposed.

years is sufciently long enough to ensure an adequate adaptation of the human metabolism to decreasing amounts of dietary iodine [20]. Thus, this mechanism does not plausibly explain the current imbalance in iodine metabolism. In contrast to this scenario, a more recent and quick increase in iodine requirement, caused by an enhanced thyroid hormone production as a result of increasing amounts of dietary carbohydrate, is well suited to explain the phenomenon of an inadequate adaptation of us humans to the environmental iodine supply (Fig. 1). The iodine content of the soil, that presumably has been sufcient during pre-agricultural periods, is not sufcient anymore to meet the increased requirement in many parts of the world, necessitating supplementation [21]. The dependency of humans on starchy food in practically all regions of the world makes IDD a global phenomenon.

Conclusions
Substantial evidence is presented that signicant changes in human nutrition during the agricultural and industrial revolution must have altered thyroid hormone levels, resulting in an increased iodine requirement. The mechanism described is well suited to explain the development of IDD as a result of these alterations.

Nutrition, evolution and thyroid hormone levels

[18] Brand-Miller JC, Colagiuri S. The carnivore connection: dietary carbohydrate in the evolution of NIDDAM. Diabetologia 1994;37:12806. [19] Putnam JJ, Allshouse JE. Food consumption, prices, and expenditures, 19701997. Washington DC: Economic Research service, US Department of Agriculture; 1999.

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[20] Rendel JM. The time scale of genetic changes. In: Boyden SV, editor. The impact of civilisation on the biology of man. Canberry: Australian National University Press; 1970. p. 2747. [21] Hetzel BS. Iodine deciency disorders (IDD) and their eradication. Lancet 1983;2:11269.