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Thiamin (also spelled thiamine) is a water-soluble B vitamin, previously known as vitamin B1 or aneurine (1). Isolated and characterized in the 1930s, thiamin was one of the first organic compounds to be recognized as a vitamin (2). Thiamin occurs in the human body as free thiamin and as various phosphorylated forms: thiamin monophosphate (TMP), thiamin triphosphate (TTP), and thiamin pyrophosphate (TPP), which is also known as thiamin diphosphate.
Thiamin pyrophosphate (TPP) is a required coenzyme for a small number of very important enzymes. The synthesis of TPP from free thiamin requires magnesium, adenosine triphosphate (ATP), and the enzyme, thiamin pyrophosphokinase.
Pyruvate dehydrogenase, α-ketoglutarate dehydrogenase, and branched chain ketoacid (BCKA) dehydrogenase each comprise a different enzyme complex found within cellular organelles called mitochondria. They catalyze the decarboxylation of pyruvate, α-ketoglutarate, and branched-chain amino acids to form acetyl-coenzyme A, succinyl-coenzyme A, and derivatives of branched chain amino acids, respectively; all products play critical roles in the production of energy from food (2). In addition to the thiamin coenzyme (TPP), each dehydrogenase complex requires a niacin-containing coenzyme (NAD), a riboflavin-containing coenzyme (FAD), and lipoic acid.
Transketolase catalyzes critical reactions in another metabolic pathway known as the pentose phosphate pathway. One of the most important intermediates of this pathway is ribose-5-phosphate, a phosphorylated 5-carbon sugar required for the synthesis of the high-energy ribonucleotides, ATP and guanosine triphosphate (GTP). It is also required for the synthesis of the nucleic acids, DNA and RNA, and the niacin-containing coenzyme NADPH, which is essential for a number of biosynthetic reactions (1, 3). Because transketolase decreases early in thiamin deficiency, measurement of its activity in red blood cells has been used to assess thiamin nutritional status (2).
Beriberi, the disease resulting from severe thiamin deficiency, was described in Chinese literature as early as 2600 B.C. Thiamin deficiency affects the cardiovascular, nervous, muscular, and gastrointestinal systems (2). Beriberi has been termed dry, wet, or cerebral, depending on the systems affected by severe thiamin deficiency (1).
The main feature of dry (paralytic or nervous) beriberi is peripheral neuropathy. Early in the course of the neuropathy, "burning feet syndrome" may occur. Other symptoms include abnormal (exaggerated) reflexes as well as diminished sensation and weakness in the legs and arms. Muscle pain and tenderness and difficulty rising from a squatting position have also been observed. Severely thiamin deficient individuals may experience seizures.
In addition to neurologic symptoms, wet (cardiac) beriberi is characterized by cardiovascular manifestations of thiamin deficiency, which include rapid heart rate, enlargement of the heart, severe swelling (edema), difficulty breathing, and ultimately congestive heart failure.
Cerebral beriberi may lead to Wernicke's encephalopathy and Korsakoff's psychosis, especially in people who abuse alcohol. The diagnosis of Wernicke's encephalopathy is based on a "triad" of signs, which include abnormal eye movements, stance and gait abnormalities, and abnormalities in mental function that may include a confused apathetic state or a profound memory disorder termed Korsakoff's amnesia or Korsakoff's psychosis. Thiamin deficiency affecting the central nervous system is referred to as Wernicke's disease when the amnesic state is not present and Wernicke-Korsakoff syndrome (WKS) when the amnesic symptoms are present along with the eye movement and gait disorders. Most WKS sufferers are alcoholics, although it has been observed in other disorders of gross malnutrition, including stomach cancer and AIDS. Administration of intravenous thiamin to WKS patients generally results in prompt improvement of the eye symptoms, but improvements in motor coordination and memory may be less, depending on how long the symptoms have been present. Recent evidence of increased immune cell activation and increased free radical production in the areas of the brain that are selectively damaged suggests that oxidative stress plays an important role in the neurologic pathology of thiamin deficiency (4).
Causes of thiamin deficiency
Thiamin deficiency may result from inadequate thiamin intake, increased requirement for thiamin, excessive loss of thiamin from the body, consumption of anti-thiamin factors in food, or a combination of these factors.
Inadequate consumption of thiamin is the main cause of thiamin deficiency in underdeveloped countries (2). Thiamin deficiency is common in low-income populations whose diets are high in carbohydrate and low in thiamin (e.g., milled or polished rice). Breast-fed infants whose mothers are thiamin deficient are vulnerable to developing infantile beriberi. Alcoholism, which is associated with low intake of thiamin among other nutrients, is the primary cause of thiamin deficiency in industrialized countries.
Conditions resulting in an increased requirement for thiamin include strenuous physical exertion, fever, pregnancy, breast-feeding, and adolescent growth. Such conditions place individuals with marginal thiamin intake at risk for developing symptomatic thiamin deficiency. Recently, malaria patients in Thailand were found to be severely thiamin deficient more frequently than non-infected individuals (5). Malarial infection leads to a large increase in the metabolic demand for glucose. Because thiamin is required for enzymes involved in glucose metabolism, the stresses induced by malarial infection could exacerbate thiamin deficiency in predisposed individuals. HIV-infected individuals, whether or not they had developed AIDS, were also found to be at increased risk for thiamin deficiency (6). The lack of association between thiamin intake and evidence of deficiency in these HIV-infected individuals suggests that they had an increased requirement for thiamin. Further, chronic alcohol abuse impairs intestinal absorption and utilization of thiamin (1); thus, alcoholics have increased requirements for thiamin.
Excessive loss of thiamin may precipitate thiamin deficiency. By increasing urinary flow, diuretics may prevent reabsorption of thiamin by the kidneys and increase its excretion in the urine (7, 8), although this remains quite controversial. Individuals with kidney failure requiring hemodialysis lose thiamin at an increased rate and are at risk for thiamin deficiency (9). Alcoholics who maintain a high fluid intake and urine flow rate may also experience increased loss of thiamin, exacerbating the effects of low thiamin intake (10).
Anti-thiamin factors (ATF)
The presence of anti-thiamin factors (ATF) in foods also contributes to the risk of thiamin deficiency. Certain plants contain ATF, which react with thiamin to form an oxidized, inactive product. Consuming large amounts of tea and coffee (including decaffeinated), as well as chewing tea leaves and betel nuts, have been associated with thiamin depletion in humans due to the presence of ATF. Thiaminases are enzymes that break down thiamin in food. Individuals who habitually eat certain raw freshwater fish, raw shellfish, and ferns are at higher risk of thiamin deficiency because these foods contain thiaminase that normally is inactivated by heat in cooking (1). In Nigeria, an acute neurologic syndrome (seasonal ataxia) has been associated with thiamin deficiency precipitated by a thiaminase in African silkworms, a traditional high-protein food for some Nigerians (11).
|Recommended Dietary Allowance (RDA) for Thiamin|
|Life Stage||Age||Males (mg/day)||Females (mg/day)|
|Infants||0-6 months||0.2 (AI)||0.2 (AI)|
|Infants||7-12 months||0.3 (AI)||0.3 (AI)|
|Adults||19 years and older||1.2||1.1|
A cross-sectional study of 2,900 Australian men and women, 49 years of age and older, found that those in the highest quintile of thiamin intake were 40% less likely to have nuclear cataracts than those in the lowest quintile (13). In addition, a recent study in 408 U.S. women found that higher dietary intakes of thiamin were inversely associated with five-year change in lens opacification (14). However, these cross-sectional associations have yet to be elucidated by studies of causation.
Because thiamin deficiency can result in a form of dementia (Wernicke-Korsakoff syndrome), its relationship to Alzheimer's disease and other forms of dementia have been investigated. A case-control study in 38 elderly women found that blood levels of thiamin, thiamin pyrophosphate (TPP), and thiamin monophosphate (TMP) were lower in those with dementia of Alzheimer's type (DAT) compared to the those in the control group (15). Interestingly, several investigators have found evidence of decreased activity of the thiamin pyrophosphate-dependent enzymes, α-ketoglutarate dehydrogenase and transketolase, in the brains of patients who died of Alzheimer's disease (16). Such findings are consistent with evidence of reduced glucose metabolism found on PET scans of the brains of Alzheimer's disease patients (17). The finding of decreased brain levels of TPP in the presence of normal levels of free thiamin and TMP suggests that the decreased enzyme activity is not likely a result of thiamin deficiency but rather of impaired TPP synthesis (18, 19). Presently, there is only slight and inconsistent evidence that thiamin supplements are of benefit in Alzheimer's disease. A double-blind, placebo-controlled study of 15 patients (ten completed the study) reported no beneficial effect of 3 grams of thiamin/day on cognitive decline over a 12-month period. In 1993, a preliminary report from another study claimed a mild benefit of 3 to 8 grams of thiamin/day in DAT, but no additional data from that study are available (20). A mild beneficial effect in patients with Alzheimer's disease was reported after 12 weeks of treatment with 100 milligrams/day of a thiamin derivative (thiamin tetrahydrofurfuryl disulfide), but this study was not placebo-controlled (21). A recent systematic review of randomized, double- blind, placebo-controlled trials of thiamin in patients with DAT found no evidence that thiamin was a useful treatment for the symptoms of Alzheimer's disease (22).
Severe thiamin deficiency (wet beriberi) can lead to impaired cardiac function and ultimately congestive heart failure (CHF). Although cardiac manifestations of beriberi are rarely encountered in industrialized countries, CHF due to other causes is common, especially in the elderly. Diuretics used in the treatment of CHF, notably furosemide (Lasix), have been found to increase thiamin excretion, potentially leading to marginal thiamin deficiency. A number of studies have examined thiamin nutritional status in CHF patients and most found a fairly low incidence of thiamin deficiency, as measured by assays of transketolase activity. As in the general population, older CHF patients were found to be at higher risk of thiamin deficiency than younger ones (23). An important measure of cardiac function in CHF is the left ventricular ejection fraction (LVEF), which can be assessed by echocardiography. One study in 25 patients found that furosemide use, at doses of 80 mg/day or greater, was associated with a 98% prevalence of thiamin deficiency (24). In a randomized, double-blind study of 30 CHF patients, all of whom had been taking furosemide (80 mg/day) for at least three months, intravenous (IV) thiamin therapy (200 mg/day) for seven days resulted in an improved LVEF compared to IV placebo (25). When all 30 of the CHF patients in that study subsequently received six weeks of oral thiamin therapy (200 mg/day), the average LVEF improved by 22%. This finding may be relevant because improvements in LVEF have been associated with improved survival in CHF patients (26). However, conclusions from studies published to date are limited due to small sample sizes of the studies, lack of randomization in some studies, and a need for more precise assays of thiamin nutritional status. Presently, the role of thiamin supplementation in maintaining cardiac function in CHF patients remains controversial.
Thiamin deficiency has been observed in some cancer patients with rapidly growing tumors. However, research in cell culture and animal models indicates that rapidly dividing cancer cells have a high requirement for thiamin (27). All rapidly dividing cells require nucleic acids at an increased rate, but some cancer cells appear to rely heavily on the TPP-dependent enzyme, transketolase, to provide the ribose-5-phosphate necessary for nucleic acid synthesis. Thiamin supplementation in cancer patients is common to prevent thiamin deficiency, but Boros et al. caution that too much thiamin may actually fuel the growth of some malignant tumors (28), suggesting that thiamin supplementation be reserved for those cancer patients who are actually thiamin deficient. Presently, there is no evidence available from studies in humans to support or refute this theory. However, it would be prudent for individuals with cancer who are considering thiamin supplementation to discuss it with the clinician managing their cancer therapy.
A varied diet should provide most individuals with adequate thiamin to prevent deficiency. In the U.S. the average dietary thiamin intake for young adult men is about 2 mg/day and 1.2 mg/day for young adult women. A survey of people over the age of 60 found an average dietary thiamin intake of 1.4 mg/day for men and 1.1 mg/day for women (12). However, institutionalization and poverty both increase the likelihood of inadequate thiamin intake in the elderly (29). Whole grain cereals, legumes (e.g., beans and lentils), nuts, lean pork, and yeast are rich sources of thiamin (1). Because most of the thiamin is lost during the production of white flour and polished (milled) rice, white rice and foods made from white flour (e.g., bread and pasta) are fortified with thiamin in many Western countries. A number of thiamin-rich foods are listed in the table below along with their thiamin content in milligrams (mg). For more information on the nutrient content of foods, search the USDA food composition database.
|Lentils (cooked)||1/2 cup||0.17|
|Peas (cooked)||1/2 cup||0.21|
|Long grain brown rice (cooked)||1 cup||0.19|
|Long grain white rice, enriched (cooked)||1 cup||0.26|
|Long grain white rice, unenriched (cooked)||1 cup||0.04|
|Whole wheat bread||1 slice||0.10|
|White bread, enriched||1 slice||0.11|
|Fortified breakfast cereal||1 cup||0.5-2.0|
|Wheat germ breakfast cereal||1 cup||4.47|
|Pork, lean (cooked)||3 ounces*||0.72|
|Brazil nuts||1 ounce||0.18|
|Spinach (cooked)||1/2 cup||0.09|
|Egg (cooked)||1 large||0.03|
*3 ounces of meat is a serving about the size of a deck of cards
Thiamin is available in nutritional supplements and for fortification as thiamin hydrochloride and thiamin nitrate (30).
The Food and Nutrition Board did not set a tolerable upper level (UL) of intake for thiamin because there are no well-established toxic effects from the consumption of excess thiamin in food or through long-term oral supplementation (up to 200 mg/day). A small number of life threatening anaphylactic reactions have been observed with large intravenous doses of thiamin (12).
Reduced blood levels of thiamin have been reported in individuals with seizure disorders (epilepsy) taking the anticonvulsant medication, phenytoin, for long periods of time (31). 5-Fluorouracil, a drug used in cancer therapy, inhibits the phosphorylation of thiamin to thiamin pyrophosphate (TPP) (32). Diuretics, especially furosemide (Lasix), may increase the risk of thiamin deficiency in individuals with marginal thiamin intake due to increased urinary excretion of thiamin (8). Moreover, chronic alcohol abuse is associated with thiamin deficiency due to low dietary intake, impaired absorption and utilization, and increased excretion of the vitamin (1).
The Linus Pauling Institute supports the recommendation by the Food and Nutrition Board of 1.2 mg of thiamin/day for men and 1.1 mg/day for women. A varied diet should provide enough thiamin for most people. Following the Linus Pauling Institute recommendation to take a daily multivitamin/multimineral supplement, containing 100% of the Daily Values (DV), will ensure an intake of at least 1.5 mg of thiamin/day.
Older adults (65 years and older)
Presently, there is no evidence that the requirement for thiamin is increased in older adults, but some studies have found inadequate dietary intake and thiamin insufficiency to be more common in elderly populations (29). Thus, it would be prudent for older adults to take a multivitamin/multimineral supplement, which will generally provide at least 1.5 mg of thiamin/day.
Written in September 2002 by:
Jane Higdon, Ph.D.
Linus Pauling Institute
Oregon State University
Updated in June 2007 by:
Victoria J. Drake, Ph.D.
Linus Pauling Institute
Oregon State University
Reviewed in June 2007 by:
Christopher Bates, D.Phil.
Honorary Senior Scientist
Formerly Head of Micronutrient Status Research
MRC Human Nutrition Research
Elsie Widdowson Laboratory
Copyright 2000-2013 Linus Pauling Institute
The Linus Pauling Institute Micronutrient Information Center provides scientific information on the health aspects of dietary factors and supplements, foods, and beverages for the general public. The information is made available with the understanding that the author and publisher are not providing medical, psychological, or nutritional counseling services on this site. The information should not be used in place of a consultation with a competent health care or nutrition professional.
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