by Ali Le Vere, Green Med Info:

Thiamin may be the missing link to treating autoimmune disease and autonomic dysfunction. Although deficiencies in this vitamin have long been considered eradicated, case studies show supplementation with this nutrient improves fatigue in autoimmune patients in a matter of hours to days

One of the common threads uniting disparate autoimmune disease labels, irrespective of diagnosis, is the debilitating fatigue that plagues patients. Although methylated B vitamins have been given ample fanfare, vitamin B1, or thiamin, has garnered far less attention in communities that emphasize the holistic management of autoimmune disease.

Functions of Thiamin

One of eight essential B vitamins, thiamin is a water-soluble vitamin that functions in the conversion of food into energy (1). The active form of thiamin, known as thiaminpyrophosphate or thiamin diphosphate, is an essential cofactor in both the citric acid cycle and pentose phosphate pathway, two enzyme-mediated pathways of carbohydrate metabolism (1). The citric acid cycle, for example, also known as the Kreb’s cycle, is a central metabolic pathway in the mitochondria that participates in the oxidative degradation of monosaccharides and other nutrients, which generates cellular energy currency in the form of adenosine triphosphate (ATP) to be used in a myriad of energy-demanding cellular reactions (1).

Inhibition of the two main enzymes of the Kreb’s cycle for which thiamin is a cofactor, pyruvate dehydrogenase complex (PDH) and alpha-ketoglutarate dehydrogenase (alpha-KGDH), leads to decreased brain levels of ATP (1). Suppression of brain ATP levels impairs degradation of dopamine in the prefrontal cortex, disrupts synthesis of the nerve-insulating myelin sheath, prevents production of the neurotransmitter acetylcholine, and reduces levels of the major inhibitory neurotransmitter gamma aminobutyric acid (GABA), which collectively leads to delirium, delusions, hallucinations, and cognitive impairment (1).

The transketolase enzyme of the cytosol-based pentose phosphate pathway (PPP), on the other hand, also requires thiamin as a cofactor (1). Transketolase converts glucose-6-phosphate into both ribose-5-phosphate and reduced nicotinamide adenine dinucleotide phosphate (NADPH), the latter of which is required to donate hydrogen atoms in chemical reactions that produce particular neurotransmitters, steroids, amino acids, fatty acids, and the master antioxidant of the body, glutathione (1). Given its centrality to these biochemical pathways which generate energy for the entire organism, the effects of thiamin deficiency are all-encompassing.

The Re-Emergence of Thiamin Deficiency Disorders

The relationship between food and berberi, the classical syndrome of thiamin deficiency, was first discovered by Japanese naval surgeon Takaki in the late nineteenth century, who found that nearly two-thirds of his crew were stricken with berberi after a long voyage. Two years later, when he loaded another warship with dry milk and meat, he noticed that a much smaller percentage of the crew succumbed to berberi, such that “Takaki concluded that the disease was caused by a lack of nitrogenous food in association with excessive intake of non-nitrogenous food” (2).

In addition to impaired reflexes, peripheral neuropathy, edema, cardiovascular abnormalities and hypesthesia, or a diminished capacity for physical sensation, signs of autonomic dysfunction such as sinus tachycardia, vasovagal syncope, mitral valve prolapse, hypotension, sweating, dermographia, and attention deficit are a prominent part of the clinical expression of berberi (2, 3). Other extreme manifestations of thiamin deficiency include Wernicke’s encephalopathy, which includes signs such as ataxia, weakness, paralysis, cognitive impairment, apathy, significant spatial and temporal disorientation, and problems with movement in the muscles around the eyes such as ocular palsies, nystagmus, and opthalmoplegia (1). These symptoms are caused by lesions in brain areas including the hypothalamic nuclei, tectal plate, periventricular nuclei, thalamus, pontine tegmentum, and abducens and oculomotor nuclei, and untreated, lead to coma and death (1).

Korsakoff’s psychosis is often a progression of Wernicke’s encephalopathy (4), and includes symptoms such as amnesia, decreased initiative, and confabulation, which means distorted, fabricated, or misinterpreted memories. Although thiamin deficiency, and its extreme incarnations in particular such as Wernicke’s encephalopathy and Korsakoff’s psychosis, is considered a medical emergency, 80% of the time these diagnoses are made during autopsy (5), mainly due to low index of suspicion, and the nonspecific clinical signs of these syndromes (1).

Although the benefit of thiamin in these classical syndromes of thiamin deficiency, which were recorded as far back as the ninth century, is uncontested, milder forms of thiamin deficiency often elude diagnosis. Marginal thiamin deficiency presents with vague symptomatology, including fatigue, irritability, abdominal pain, frequent headaches, and a decline in growth rate in children (6). The World Health Organization states, in fact, that, thiamin deficiency is a clinical diagnosis confirmed upon improvement with thiamin administration:

The symptoms of mild thiamin deficiency are vague and can be attributed to other problems, so that diagnosis is often difficult…The symptoms of mild thiamin deficiency clinically improve by the administration of thiamin.(7)

In the minds of conventional providers, deficiency diseases have been eradicated in the industrialized world; however, unbeknownst to the medical establishment, it is our Western diets that are facilitating the re-emergence of these diseases considered long-abolished:

Perhaps, in the light of more modern knowledge, it is possible to state that high simple carbohydrate malnutrition can cause symptoms of early beriberi. Since beriberi conjures up an unacceptable concept in the mind of many modern physicians it is probable that it would not be considered in differential diagnosis. It is very likely that many of the poorly understood symptomatology seen today that responds to nutrient therapy is caused by a mixture of marginal classic nutritional diseases, including beriberi, pellagra and scurvy.(2)

Efficacy of Thiamin in Inflammatory Bowel Disease

Especially encouraging are the results of a small open-label pilot study of thiamin use in patients with inflammatory bowel diseases (IBD), including Crohn’s disease and ulcerative colitis, who presented with fatigue and lingering extra-intestinal symptoms despite their diseases being characterized as quiescent or in remission (8). Patients, all of whom had normal thiamin levels at the commencement of the study, were treated orally with 600 milligrams per day of thiamin, with additional doses in increments of 300 mg per day for those cases in which regression of fatigue was not considered satisfactory, up to a total of 1,500 mg per day (8). In other words, the dose was defined empirically, with calibration based upon subject weight and according to symptomatic remission.

All but two of the twelve patients exhibited a complete regression of fatigue, and in the remaining two, near complete regression was observed (8). Moreover, one hundred percent of patients reported complete regression of symptoms associated with fatigue (8). Impressively, the majority of patients also displayed improvements in intestinal function, with marked reductions in the number of diarrhetic episodes (8).

Notably, in one of the series of case studies presented, fatigue disappeared completely after intramural thiamin injection, and authors mention that “within 20 days, the patient regained complete wellness” (8). This study confirmed findings by Magee and colleagues, who found that consumption of thiamin-rich foods decreases disease activity in patients with ulcerative colitis (9).

Effect of Thiamin in Hashimoto’s Thyroiditis

Another series of case reports published in The Journal of Alternative and Complementary Medicine chronicles the use of thiamin in patients with Hashimoto’s thyroiditis who had persistent symptoms such as fatigue, depression, anxiety, sleep disruption, impaired memory and concentration, dry skin, and cold intolerance despite normal thyroid parameters (10). Patients, all of whom exhibited normal blood levels of thiamin and TPP prior to treatment, were administered either 600 mg per day of oral thiamin or 100 mg per mL of thiamin administered parenterally every four days, depending on weight (10).

In the two patients given oral thiamin, complete regression of fatigue occurred within 3 to 5 days, whereas fatigue regressed within 6 hours in the patient given intramuscular thiamin therapy (10). Although case studies rank low on the hierarchy of evidence-based data, and underscore the need for higher quality research, the mechanism linking functional thiamin deficiency to autoimmune-based fatigue is so plausible that the study authors assert:

While further studies are necessary to confirm our findings, we strongly believe that our observations represent an important contribution to the relief of many patients.(10)

Reasons Underlying Thiamin Deficiency in Autoimmunity

As indicated by the IBD pilot study in which all patients exhibited normal levels prior to treatment, yet still responded favorably to thiamin supplementation, tests of thiamin and thiamin pyrophosphate (TPP), the active form of thiamin, may be of no value in identifying functional thiamin deficiency (8).

Normal serum levels of thiamin and TPP, in fact, indicate normal thiamin absorption by the small intestine (8). Researchers instead attribute the symptoms of thiamin deficiency that appeared in these autoimmune patients in both studies to either structural enzymatic defects or to dysfunction of the vitamin B1 active intracellular transport mechanism from the blood to the mitochondria (8). Administration of large quantities of vitamin B1, on the other hand, is able to circumvent this abnormality:

The administration of large quantities of vitamin B1 orally increases the concentration in the blood to levels in which the passive transport restores the normal glucose metabolism. The glucose metabolism of all organs goes back to normal values and fatigue disappears.(8)

As an alternative explanation, one author in the New England Journal of Medicine proposes that a deficiency in activity of one thiamin transporter can cause another to pick up the slack when high doses of thiamin are administered. This occurs because one member of the solute carrier (SLC) gene family of transporter proteins, which possess structural similarity, can substitute for the function of another.

In other words, at large doses, thiamin can induce expression of the solute carrier gene family member SLC19A2, which encodes the human thiamin-only transporter 1 (hTHTR1), in order to compensate for defects in SLC19A3, which encodes the human thiamin and biotin transporter 2 (hTHTR2) (11). Increasing the concentration of blood thiamin also augments the chances that it crosses the blood brain barrier (BBB) to correct neurological deficits, since thiamin penetration of the BBB occurs via passive diffusion, an energy-independent process, when there is a surplus of thiamin available (12).

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