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From ... in Biology —

Vitamin B1 Is Vital to Protect Against Infectious Disease

Vitamin B1 Is Vital to Protect Against Infectious Disease

STORY AT-A-GLANCE

While a limited number of drugs have been enlisted in the treatment of severe coronavirus (SARS-CoV-2) infection, a number of nutritional supplements have risen to the forefront for their apparent usefulness. In addition to quercetin , zinc and vitamins C and D, vitamin B1 (thiamine) may be vital to protect against infectious respiratory illness. Thiamine is also part of Dr. Paul Marik's sepsis treatment, which calls for 1,500 milligrams (mg) of intravenous ascorbic acid every six hours, 200 mg of thiamine every 12 hours and 50 mg of hydrocortisone every six hours. Sepsis, as you may have heard, is a major contributor in infiuenza deaths in general, and a primary cause for COVID-19 deaths specifically. In one clinical trial, Marik, [formerly] a critical care doctor at Sentara Norfolk General Hospital in East Virginia, showed his treatment reduced sepsis-related mortality nearly fivefold. More recent research, published online January 9, 2020, found Marik's sepsis protocol lowered mortality in pediatric patients as well. At the 30-day mark, controls and the hydrocortisone-only groups had a mortality rate of 28% while the treatment group had a mortality rate of just 9%.

Vitamin C, Thiamine and Steroids Have Synergistic Effects

All three ingredients in Marik's sepsis protocol have synergistic effects, which seems to be why it's so effective. Vitamin C is well-known for its ability to prevent and treat

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infectious diseases on its own. Infiuenza, encephalitis and measles have all been successfully treated with high-dose vitamin C, and previous research has shown it effectively lowers proinfiammatory cytokines and C-reactive protein. Vitamin C and corticosteroids, however, have been shown to work synergistically. This was demonstrated in a study by Marik in collaboration with John Catravas, Ph.D., a pharmacology researcher at Old Dominion University, and others, in which endothelial cells from lung tissue were exposed to lipopolysaccharide — a type of endotoxin found in patients with sepsis — in the absence or presence of ascorbic acid and hydrocortisone. Interestingly, when either vitamin C or the steroid was administered in isolation, very little improvement in endothelial barrier function occurred. When administered together, however, the infection was successfully eradicated and the cells were restored to normal. The addition of thiamine (vitamin B1) is also important. Not only is thiamine required for metabolism of some of the metabolites of vitamin C, thiamine deficiency syndrome (beriberi) has many similarities to sepsis, and thiamine deficiency is relatively common in critically ill patients. As noted in a 1955 study, thiamine deficiency is also prevalent in pulmonary tuberculosis, and the more severe the case, the more severe the thiamine deficiency. Studies have also shown thiamine can be helpful for a long list of diseases and disorders, including mitochondrial disorders, heart failure, delirium, thyroid fatigue and Hashimoto's (a thyroid autoimmune disorder). These and other health effects may help explain why thiamine works so well in conjunction with vitamin C and hydrocortisone for sepsis. You can learn more about Marik's sepsis protocol in “ Vitamin C — A Game Changer in Treatment of Deadly Sepsis ,” along with commonsense recommendations for how to

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lower your risk of sepsis in the first place. You can also review Marik's PowerPoint presentation, “ Hydrocortisone, Ascorbic Acid and Thiamine for the Treatment of Severe Sepsis and Septic Shock ,” presented at the 2020 Critical Care Reviews meeting in Australia.

Thiamine Deficiency Implicated in Severe Infections

Thiamine deficiency has also been implicated in severe infections specifically. A 2016 study in the journal Psychosomatics sought to investigate this by looking at 68 patients with Korsakoff syndrome, a memory disorder caused by severe thiamine deficiency. While thiamine deficiency is often the result of alcohol misuse, it's also associated with chronic infections, poor nutrition and/or malabsorption. As explained by the Alzheimer's Association, “Thiamine helps brain cells produce energy from sugar. When levels fall too low, brain cells cannot generate enough energy to function properly.” In the Psychosomatics study, they found that 35 of 68 Korsakoff patients suffered severe infections during the acute phase of the illness, including meningitis, pneumonia and sepsis. According to the authors, “Infections may be the presenting manifestation of thiamine deficiency.”

Thiamine Helps Regulate Your Immune Function

Another study published in 2018 found thiamine helps limit Mycobacterium tuberculosis (MTB) by regulating your innate immunity. According to this paper:

“... vitamin B1 promotes the protective immune response to limit the survival ofMTB within macrophages and in vivo through regulation of peroxisomeproliferator-activated receptor γ (PPAR-γ).
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Vitamin B1 promotes macrophage polarization into classically activatedphenotypes with strong microbicidal activity and enhanced tumor necrosisfactor-α and interleukin-6 expression at least in part by promoting nuclearfactor-κB signaling.In addition, vitamin B1 increases mitochondrial respiration and lipid metabolismand PPAR-γ integrates the metabolic and infiammatory signals regulated byvitamin B1 ... We demonstrate that vitamin B1 enhances anti-MTB activities inmacrophages and in vivo by down-regulating PPAR-γ activity.Our data demonstrate important functions of thiamine VB1 in regulating innateimmune responses against MTB and reveal novel mechanisms by which vitaminB1 exerts its function in macrophages.”

The Link Between Thiamine Deficiency and Fever

Thiamine deficiency is also associated with the development of high fever, and according to a letter to the editor, “Is Parenteral Thiamin a Super Antibiotic?” published in the Annals of Nutrition & Metabolism in 2018, thiamine injections are “likely to eradicate microbial infections” causing the fever. The authors cite some clinical case reports in which thiamine injections were able to reverse a number of acute illnesses in which high fever was a factor, including one case where the patient presented with high fever, headache and asphyxia (feelings of suffocation), and another where a comatose patient had high fever and severe pneumonia.

“... another laborer with much milder pneumonia, 38°C fever with few rales inthe left lung died within 24 h, although a full dose of penicillin G was used, butno thiamin was given,”

the authors note.

“This sharp contrast between the two cases made such a deep impression thatit was strongly remembered. Fifty-six years later, it became a life-savingsuggestion for a critical case with fatal viral pneumonia.”
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The authors go on to detail an even more remarkable case involving a 38-year-old Chinese woman who was brought to the hospital with high fever (39 to 40 degrees C), pain, swollen legs and bloody sputum. Laboratory testing showed she was anemic and had low platelets, severe pneumonia, femoral thromboses and heart failure. She also tested positive for hepatitis C.

“An exhaustive identification study revealed that the pathogen of herpneumonia was diagnosed to be an unknown kind of virus,”

the authors note.

“Pulmonary lesions were extremely severe, strange, and rare with multiple smallperforations in the left lung ...After 12 days of immunoglobulin, anti-viral, antithrombotic, and antipyreticmedication, she was about to die when her family promptly carried her home ...At home, thiamin 200 mg and VB complex 1 ampule (containg thiamin 10 mg,ribofiavin 2 mg, niacinamide 30 mg, pyridoxin 2 mg, pantothenic acid 1 mg)were injected thrice daily.Temperature returned to normal after 2 days and leg edema disappeared in 5days ... After 58 days, she was checked in the Beichen Hospital ... The resultsrevealed a normal heart; hepatitis C negative ... less effusion in the left thoraciccavity; pleural thickness especially on the left side but no adhesion. Lungperforation was absent ... She thereafter enjoyed excellent health without anysign of embolism or pneumonia recurrence.”

About 10 months after her initial hospitalization, she underwent a second follow-up, which revealed normal blood counts and electrocardiography. Her lungs also looked completely normal on X-rays, “with no thickening or adhesion of pleura except for a few texture thickenings in the lungs.” According to the authors, this case made them wonder whether thiamine might be “a super antibiotic.” “It seemed to be surely so and was emerging to be a powerful alternative in the event of antibiotics failing,” they said.

Thiamine Deficiency Might Impact Pandemics

The World Health Organization has also published information about the importance of thiamine and how to prevent deficiency during major emergencies. According to WHO:

“Thiamine deficiency occurs where the diet consists mainly of milled whitecereals, including polished rice, and wheat fiour, all very poor sources ofthiamine. Thiamine deficiency can develop within 2-3 months of a deficientintake and can cause disability and death.”

Other evidence suggests thiamine insuficiency or deficiency can develop even faster than that, perhaps as quickly as two weeks, as its half-life in your system is only nine to 18 days. The WHO report also points out that “Thiamine deficiency occurs sporadically in people who are socially isolated, suffer loss of appetite and self-neglect” — a point that is particularly pertinent in current circumstances of global “shelter in place” requirements. What's more:

“The requirement of thiamine is increased when carbohydrates are taken inlarge amounts and is raised during periods of increased metabolism, forexample, fever, muscular activity, hyperthyroidism and also during pregnancyand lactation. A diet based on polished rice is high in carbohydrates whichaugments the thiamine requirement and is compounded by a low thiaminecontent.”

Aside from rice, junk food of all kinds tends to be loaded with carbohydrates as well, which could necessitate a higher-than normal thiamine intake to prevent side effects of thiamine deficiency. In adults, thiamine deficiency is divided into two primary types: Dry beriberi (thiamine deficiency with peripheral neuropathy) — Polyneuropathy with paraesthesia of the extremities (especially the legs), reduced knee jerk and other tendon refiexes, progressive severe weakness and wasting of muscles, and greatly increased susceptibility to infections.

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Wet beriberi (thiamine deficiency with cardiomyopathy) — Edema (especially of the legs, but also the trunk and face), high cardiac output, ventricular failure, sinus rhythm, dilatation of arterioles, depressed erythrocyte and leukocyte transketolase, elevated serum lactate and pyruvate, and pulmonary congestion with pleural effusions; death from congestive heart failure may occur abruptly. By dramatically increasing susceptibility to infections, thiamine deficiency could potentially have the ability to impact the spread of just about any pandemic infectious disease.

The Importance of Thiamine in Septic Shock

With regard to sepsis — which is a primary reason why people die from COVID-19 — thiamine may be of vital importance. In a Journal of Thoracic Disease article with the evocative title, “Do Not Forget to Give Thiamine to Your Septic Shock Patient!” the authors stress that:

“[Thiamine] is a water-soluble vitamin that is an indispensable constituent ofcellular metabolism. A lack of this vitamin can, therefore, be potentially life-threatening ... Thiamine diphosphate, also known as thiamine pyrophosphate(TPP) ... is the most important and active form of this vitamin ...Thiamine pyrophosphate ... acts in concomitance with magnesium to expeditevarious mitochondrial oxidative decarboxylation reactions.Thiamine pyrophosphate is necessary as a cofactor for branched-chainketoacid dehydrogenase complex essential for the metabolism of the branched-chain amino acids and for two critical complexes required for the mitochondrialsynthesis of adenosine triphosphate (ATP): pyruvate and 2-oxoglutaratedehydrogenase (α-ketoglutarate) complexes ...Also, TPP serves as a coenzyme for transketolase, a cytosolic enzymeimplicated in the pentose phosphate pathway that functions in maintaining cell
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redox status through the production of NADPH (reduced nicotinamide adeninedinucleotide phosphate) and glutathione ...Lack of thiamine leads to alterations in intermediate metabolism that end-up inlactic acidosis ...Thiamine deficiency is also prevalent in septic shock patients, with ratesranging from 20% to 70% depending on the cutoff value used to define thepresence of thiamine deficiency. Lack of thiamine reduces the fiux of pyruvateto the Krebs cycle, thus increasing lactate production by altering the aerobicmetabolism.In a prospective, observational study, Donnino et al. investigated therelationship between thiamine levels and lactic acidosis in 30 septic shockpatients ...After excluding patients with abnormal liver function tests, the authorsobserved a significant negative correlation between thiamine concentrationsand lactic acidosis, implying a potential association between thiamine levelsand lactic acidosis in septic shock patients with normal liver function.Thus, the possibility that by decreasing the activity of pyruvate dehydrogenasecomplex, thiamine deficiency can contribute to increased production of lacticacid in critically ill septic patients exists.”

The authors cite additional research strongly suggesting “the administration of thiamine is advantageous in septic shock patients with severe thiamine deficiency (thiamine level ≤ 7 nmol/L).” Considering the safety of thiamine, even at high doses, the authors stress that “septic shock patients should be given thiamine ... without waiting for the results of thiamine level.” The European Society for Clinical Nutrition and Metabolism guidelines for patients in intensive care situations are 100 to 300 mg of thiamine per day “during the first three days in the ICU for all patients with suspected thiamine deficiency.”

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In cases of septic shock, however, dosages of 500 mg may be required. According to “Do Not Forget to Give Thiamine to Your Septic Shock Patient!”:

“Because anaphylaxis has been reported in rare instances, guidelines in theUnited Kingdom have recommended that thiamine should be administered over15- to 30-minute interval in a mixture of saline solution or dextrose, with theintention of averting potential adverse reactions.”

Vitamins C, D, Thiamine and Magnesium for Critical Illness

A 2018 report in Intensive Care Medicine also focuses on thiamine — here in conjunction with vitamins C and D. It cites research showing septic shock patients with thiamine deficiency who were given thiamine had far lower mortality (13%) than those who did not receive it (46%). They were also far less likely to suffer kidney failure. Like thiamine, acute vitamin C deficiency is very common during critical illness yet tends to go unnoticed. As noted in this report, “Acute vitamin C deficiency may contribute to hypotension, exaggerated infiammation, capillary leakage, microcirculatory compromise, oxidative organ injury, and impaired immune defense and wound healing.” Vitamin D deficiency is also common, and can worsen illness and increase the risk of death from acute illness. According to the authors of this report:

“Preliminary data using novel methods suggest that glutathione and glutamatepathway metabolism, which are important for redox regulation andimmunomodulation, are affected by vitamin D status ...The VITdAL-ICU study (n = 475) did not find a difference in the length of hospitalstay between groups, but there was a significant reduction in mortality in thepredefined subgroup of patients with severe vitamin D deficiency. The mostrecent meta-analysis concludes that vitamin D in the ICU may be associatedwith mortality reduction.”
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Surprisingly, magnesium has not been given much, if any, attention in all this. It may be just as important for the prevention and treatment of infection, however, seeing how magnesium is required for the activation of both thiamine and vitamin D.

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