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bola outbreaks have occurred in Africa on previous Ebola after being in contact with an Ebola sufferer. Tracking his
occasions without significant outbreaks in Europe, Asia, contacts is now also paramount to help prevent an outbreak in
Americas or Australia. Transmission does not occur the USA an unlikely scenario, but containment is by far and
easily and is mainly through exchange of bodily fluids. Personal away the best method at this stage. Unfortunately the survival
hygiene/poor diet and compromised immunity associated with rate once patients have contracted this particular strain of Ebola
squalid living conditions almost certainly play major roles in is only around about 50%. Some patients have been treated
disease transmission. As with most diseases personal hygiene with the plasma of patients (passive immunity by the contained
habits which are adequate under normal circumstances antibodies) who have recovered from Ebola but this carries the
may be inadequate when challenged with a large dose of distinct possibility of transmitting other serious diseases such
Ebola so countries outside of Africa should not necessarily as Hepatitis and AIDS not all patients treated by this method
consider themselves immune from a possible outbreak. This have survived but this method has worked for several health
phenomenon has been recognised by the CDC and government care workers. Other methods for producing the appropriate
in the USA who have sent many health care workers and troops antibodies are currently under intense development but will be
trained to assist in helping to contain and treat such epidemics very costly and an early phase 1 clinical trial on a proposed
and to follow up contacts of those who have or had the Ebola vaccine has demonstrated safety. However it will still be another
disease. To date thousands of Ebola victims have died in this 12 months before a phase 2 trial is completed and of course
current outbreak in West Africa and there is now a recent report there is no guarantee at this stage that it will be sufficiently
of a US citizen returning from West Africa who is critically ill with successful or safe in a much larger African population.
many clinicians currently use Vitamin C. Another clinical trial using IVC in septic shock is
now recruiting, with the IVC dose to be 66mg/kg/hour of
high dose IV Vitamin C for a variety peripheral intravenous Vitamin C infusion for 24 hour duration,
maximum total of 200 grams. This is the typical dose used
of acute viral infections, IV Vitamin C is now being used in in burns units ix. In cancer clinical trials IVC is typically used
humans with sepsis, and there are significant similarities at doses from 11.5 g/kg. In a clinical trial on IVC in ovarian
cancer by Ma et al.xi they used a dose-escalating protocol,
between Ebola and sepsis presentations. Vitamin C given with final dose of either 75 or 100 g per infusion depending on
intravenously to Ebola patients would seem to be a wise step. peak plasma concentration of each individual. The target peak
plasma concentration of ascorbate was 350 to 400 mg/dl (20 to
23mM). In the original clinical burns trial conducted in Japan
Given this knowledge it is apparent that the excessive by Tanaka et al.viii IVC was used at a dose of 66 mg/kg/hour
inflammatory cascade and pathological derangements of Ebola for 24 hours. This works out at approx. 100g IVC per 24 hours
in disrupting microcirculation share some common pathways for a typical patient. The vitamin C dramatically reduced the
with other derangements of immune response, such as septic resuscitation fluid requirements in the treatment group.
shock and severe burns.
So what has this got to do with Vitamin C? There are now Some Mechanisms of Vitamin C
many animal studies on the use of high dose Vitamin C in
experimentally induced septic shock. And now there are also
in septic shock (microcirculation
SUCCESSFUL human clinical trials of high dose intravenous disruption, also occurs in
Vitamin C in septic shock v with more recruiting and on the
way vi. In particular intravenous Vitamin C is known to rapidly severe burns)
repair the microcirculation in septic shock and rapidly restore
the response to vasoconstrictors vii. High dose intravenous These key points below are taken directly from Wilson et al vii:
Vitamin C has also been shown clinically to stabilise Sepsis is associated with mal-distribution of blood flow
microcirculation and dramatically reduce fluid resuscitation within organs and loss of microvascular control of tissue
requirements in severe burns viii, ix. So much so that high dose oxygenation, as well as with arteriolar hypo-responsiveness to
intravenous Vitamin C is now used routinely in these patients vasoconstrictors and vasodilators
in many burns units x. Given the common factor of disruption Tissue hypoxia may precipitate organ failure. Indeed,
of the micro-circulation in septic shock, burns and Ebola it is microvascular dysfunction is a strong predictor of death and
reasonable to suggest that high dose Vitamin C could also one-third of severe sepsis patients die of organ failure even
impact the course of an Ebola infection. An optimistic clinical when shock is prevented
expectation is that the natural course of the disease could be Sepsis and tissue hypoxia are also associated with increased
slowed significantly, enough for the infected host to mount an production of reactive oxygen species (ROS) and peroxynitrite
appropriate immune defence against the infection. In other that deplete antioxidant molecules and cause oxidative stress
words we would hope that high dose Vitamin C could buy time ROS modulate redox-sensitive intracellular signalling pathways
and also deal directly with some of the nastier consequences that control the expression of genes critical to the initiation
of Ebola infection. If this were the case then a lot of lives and perpetuation of sepsis; these genes encode proteins
could be saved. that synthesize inflammatory cytokines, increase blood
coagulation, and alter endothelial cells regulation of blood
Lets review some uses of Vitamin C in sepsis and burns and pressure and capillary blood flow
compare the similarities between them and Ebola infection.
Histamine
Ebola - Similarities with Sepsis?
Low plasma ascorbate has been demonstrated in infection and
critically ill patients. Multiple organ failure and survival in critically While there are obvious differences between an Ebola
ill patients has been inversely related to plasma ascorbate infection and a typical sepsis patient, the two do share
concentration xii. Also, plasma histamine levels are inversely some common pathological events. In both can be seen a
associated with plasma ascorbate levels xiii. Elevated histamine diffuse overproduction of a range of cytokines which are both
levels are associated with capillary leakage and shock. damaging to the microcirculation and serve to increase the
damage by further immune system recruitment. In both we see
a derangement of Nitric Oxide. In both we see systemic organ
failure and the development of shock.
Ebola specific mechanisms
Vitamin C has been show in vitro, in animals and in humans
These key points below are taken directly from Infection to interfere with sepsis signalling. It has been shown to
Mechanism of Genus Ebolavirus MicrobeWiki iv dramatically reduce the cytokine production in uncontrolled
The span of time from onset of symptoms to death is usually sepsis signalling, to normalise and stabilise NO levels and
between 6 and 16 days. By the second week of the infection, to dramatically reduce fluid lost from the microvasculature in
the patient will either experience a full recovery or undergo severely burned patients.
systemic multi-organ failure. Mortality rates are generally high,
ranging from 50-90% depending on the specific strain. The So at this stage, given the similarities, and given the
cause of death is normally due to hypovolemic shock or organ effectiveness of high dose Vitamin C in septic patients, it is a
failure. While haemorrhages can be severe and have been the reasonable assertion to suggest that it is worth a go in Ebola
calling card of this virus, they are actually present in fewer than patients. Wilson xii makes the point that for effectiveness in
half of patients
In the typical presentations of patients with sepsis Vitamin C is Given that many clinicians currently use high dose IV Vitamin
shown clearly to rapidly restore microcirculatory homoeostasis vii. C for a variety of acute viral infections, that IV Vitamin C is now
It is reasonable to expect these sorts of effects in Ebola being used in humans with sepsis, and that there are significant
infections. For a replication of the dramatic effects seen in similarities between Ebola and sepsis presentations, Vitamin C
sepsis the Vitamin C should be given intravenously in high dose, given intravenously to Ebola patients would seem to be a wise
at least in a dose seen to be effective in a sepsis clinical trial v. step. At least it may buy some time for the patient to minimise
As already stated some would not consider this dose to be high microvascular disruption and to make a recovery via normal
enough. Vitamin C is not toxic so a conservative dose in a life immune defence which will also be supported and stimulated
threatening situation such as Ebola infection may not be wise. by Vitamin C.
Barr viral infection. Med. Sci. Monit.. 2014 05; 20(): 725-32. PMID: Kressel J, Regnet T, Rosenberg A, Neurath MF, Molderings GJ, Raithel
24793092 M, Intravenous infusion of ascorbic acid decreases serum histamine
concentrations in patients with allergic and non-allergic diseases.
Yuan S, Drugs to cure avian influenza infection--multiple ways to
ii
Naunyn Schmiedebergs Arch. Pharmacol. 2013 May; (): . PMID:
prevent cell death. Cell Death Dis. 2013 10; 4(): e835. PMID: 24091678 23666445
Sullivan N, Yang ZY, Nabel GJ, Ebola virus pathogenesis: implications
iii
xiv
Sanchez A, Lukwiya M, Bausch D, Mahanty S, Sanchez AJ, Wagoner
for vaccines and therapies. J. Virol.. 2003 Sep; 77(18): 9733-7. PMID: KD, Rollin PE, Analysis of human peripheral blood samples from
12941881 fatal and nonfatal cases of Ebola (Sudan) hemorrhagic fever: cellular
Infection Mechanism of Genus Ebolavirus MicrobeWiki. https://
iv responses, virus load, and nitric oxide levels. J. Virol.. 2004 Oct; 78(19):
microbewiki.kenyon.edu/index.php/Infection_Mechanism_of_Genus_ 10370-7. PMID: 15367603
Ebolavirus xv
Levy R, Shriker O, Porath A, Riesenberg K, Schlaeffer F, Vitamin C
v
Fowler AA, Syed AA, Knowlson S, Sculthorpe R, Farthing D, DeWilde for the treatment of recurrent furunculosis in patients with imparied
C, Farthing CA, Larus TL, Martin E, Brophy DF, Gupta S, , Fisher BJ, neutrophil functions. J. Infect. Dis.. 1996 Jun; 173(6): 1502-5. PMID:
Natarajan R, Phase I safety trial of intravenous ascorbic acid in patients 8648230
with severe sepsis. J Transl Med. 2014 01; 12(): 32. PMID: 24484547 Yonemoto et al; Enhanced Lymphocyte Blastogenesis by Oral
xvi
Shimazaki S. Reduction of resuscitation fluid volumes in severely Johnston CS, Martin LJ, Cai X. Antihistamine effect of supplemental
xviii
burned patients using ascorbic acid administration: a randomized, ascorbic acid and neutrophil chemotaxis. J Am Coll Nutr. 1992
prospective study. Arch Surg. 2000 Mar;135(3):326-31. PMID: Apr;11(2):172-6
10722036 Siegel BV. Enhanced interferon response to murine leukemia virus by
xix
Kahn SA, Beers RJ, Lentz CW, Resuscitation after severe burn injury
ix ascorbic acid. Infect Immun. 1974 Aug;10(2):409-10. PMID: 4368679
using high-dose ascorbic acid: a retrospective review. J Burn Care Res. xx
Moens B, Decanine D, Menezes SM, Khouri R, Silva-Santos G,
2011; 32(1): 110-7. PMID: 21131846 Lopez G, Alvarez C, Talledo M, Gotuzzo E, de Almeida Kruschewsky
x
Sartor Z, Kesey J, Dissanaike S, The Effects of Intravenous Vitamin C R, Galvo-Castro B, Vandamme AM, Van Weyenbergh J, Ascorbic
on Point-of-Care Glucose Monitoring. J Burn Care Res. 2014 Aug; (): . acid has superior ex vivo antiproliferative, cell death-inducing
PMID: 25127026 and immunomodulatory effects over IFN- in HTLV-1-associated
myelopathy. PLoS Negl Trop Dis. 2012 07; 6(7): e1729. PMID: 22848768
Ma Y, Chapman J, Levine M, Polireddy K, Drisko J, Chen Q, High-
xi
vitamin C and zinc and effect on clinical conditions. Ann. Nutr. Metab..
2006 12; 50(2): 85-94. PMID: 16373990