Thiamin is essential in carbohydrate metabolism and nerve function. Severe thiamin deficiency results in the nerve and heart disease beri beri. Less severe deficiency results in non-specific signs: malaise, loss of weight, irritability, and confusion.
Low thiamin status has been reported in alcoholics, older adults, HIV/AIDS patients, subjects with malaria, and pregnant women with prolonged nausea and vomiting in pregnancy. The presentation of thiamin deficiency is variable, apparently affected by such factors as age, calorific (especially carbohydrate) intake, and presence/ absence of other micronutrient deficiencies.
The classic syndrome resulting from thiamin deficiency in humans is beriberi. This disease is prevalent in Southeast Asia, where polished rice is the dietary staple. It appears to be associated with the consumption of diets rich in highly digestible carbohydrates, but marginal or low in micronutrients. The general symptoms of beriberi are anorexia, cardiac enlargement, lassitude, muscular weakness, burning of the skin, loss of knee and ankle jerk responses (with subsequent foot and wrist droop), and breathlessness on exertion. Beriberi occurs in three clinical types. Dry (or neuritic) beriberi occurs primarily in adults; it is characterized by peripheral neuropathy consisting of symmetrical impairment of sensory and motor nerve conduction affecting the arms and legs. Wet (oedematous) beriberi (also called cardiac beriberi) involves as its prominent signs oedema, tachycardia, and congestive heart failure. Infantile (or acute) beriberi occurs in breastfed infants of thiamin-deficient mothers, most frequently at 2–6 months of age. It has a rapid onset and may have both neurologic and cardiac signs, with death due to heart failure usually within a few hours. Their mothers typically show no signs of thiamin deficiency.
Thiamin is absorbed in the upper small intestine by active transport and passive diffusion. Most of the thiamin in serum is bound to protein, chiefly albumin. About 90% of the total thiamin in blood is contained in red blood cells. Thiamin uptake and secretion appears to be mediated by the thiamin transporters. The adult human stores only 25–30 mg thiamin, most of which is in skeletal muscle, heart, brain, liver, and kidneys.
The turnover of thiamin varies between tissues, but is generally high. Thiamin in excess of that which binds in tissues is rapidly excreted. With an estimated half-life of 10–20 days in humans, thiamin deficiency states can deplete tissue stores within a couple of weeks. Studies with fasting and undernourished soldiers have shown that food restriction increases the rate of thiamin excretion (1). Thiamin is excreted in the urine and small amounts of the vitamin have also been reported to be lost in sweat (2).
Thiamin is generally well tolerated. Most of the available information relating to its toxic potential is for thiamin hydrochloride. Up to 300 mg/day) are used therapeutically (for example, to treat frank beriberi, Wernicke–Korsakoff syndrome, etc.) in humans without adverse reactions.
SOURCES OF THIAMIN
Thiamin is widely distributed in foods, but most contain only low concentrations of the vitamin. The richest sources are yeasts (e.g., dried brewer’s and baker’s yeasts) and liver (especially pork liver); however, cereal grains comprise the most important sources of the vitamin. Whole grains are typically rich in thiamin; however, the vitamin is distributed unevenly in grain tissues. The greatest concentrations of thiamin in grains are typically found in the thin layer between the germ and the endosperm (the starchy interior) and the germ. The starchy interior is quite low in the vitamin. Therefore, milling to degerminate grain to remove the highly unsaturated oils associated with the germ to produce a product that will not rancidify and so, has a longer storage life, significantly reduces the thiamin content. In foods derived from plants, thiamin occurs predominantly as free thiamine. In contrast, thiamin occurs in animal tissues almost entirely (95–98%) in phosphorylated forms, the predominant form (80–85%) being the coenzyme thiamin diphosphate, also called thiamin pyrophosphate (TPP).
Thiamin is susceptible to destruction by several factors including neutral and alkaline conditions, heat, oxidation, and ionizing radiation. It is stable at low pH (pH <7), but decomposes when heated, particularly under non-acidic conditions. Protein-bound thiamin, found in animal tissues, is more stable to such losses. Thiamin is stable during frozen storage; substantial losses occur during thawing, however, mainly due to removal via drip fluid.
Thiamin in foods can be limited by several naturally occurring compounds, including sulphites which react with it and enzymes that destroy it. Caffeic, chlorogenic and tannic acids found in certain fruits react with thiamin to yield a non-absorbable form.
FUNCTIONS OF THIAMIN
Thiamin is an essential cofactor for five enzyme complexes involved in carbohydrate and fatty acid metabolism. Each of these requires thiamin in the form of TPP which serves as a classic coenzyme with binding facilitated by magnesium, which is therefore essential for enzyme activity. A rare genetic defect in one thiamin enzyme facilitated complex results in the condition called maple syrup urine disease which presents in infants as lethargy, seizures, and, ultimately, mental retardation. The condition can be detected by the maple syrup odour of the urine, which results from the presence of the ketoacid leucine. Some cases respond to high doses (10–200 mg/day) of thiamin.
Thiamin has a vital role in nerve function, and the signs of thiamin deprivation are mainly neurologic ones. Thiamin has been identified in the mammalian brain, in synaptic membranes, and in cholinergic nerves. Brain concentrations tend to be resistant to changes with thiamin deprivation suggesting some degree of homeostatic control in that organ. Thiamin deprivation has been shown to cause oxidative stress, alter neurotransmitter metabolism, and cause dysfunction of the blood–brain barrier (3).
The neurologic function of thiamin is thought to involve its essential role in the metabolism of glucose, on which the brain depends for its energy source. However, should the brain become deprived of thiamin, brain ATP levels remain unaffected probably due to the recruitment of γ-aminobutyric acid (GABA), which in addition to its role as a neurotransmitter may also yield energy under these conditions. This may explain the anorexia characteristic of thiamin deficiency, as increased GABA flux has been shown to inhibit feeding in animals. It has been suggested that thiamin may be involved the synthesis of myelin. Several neurologic conditions have indicated key roles of thiamin in nervous function.
This psychosis includes severely impaired retentive memory and cognitive function, apathy and confabulation. It is caused by thiamin insufficiency with excessive alcohol consumption (4). Signs range from mild confusion to coma. Chronic alcohol consumption can lead to thiamin deficiency in two ways: by reducing thiamin intake due to the displacement of foods rich in thiamin (and other nutrients) by alcohol; and by impairing thiamin absorption and utilization and, probably, the cellular uptake of the vitamin. The risk of Wenicke–Korsakoff syndrome is not limited to heavy alcohol users. The thiamin-responsive syndrome has been diagnosed in non-alcoholic patients with nausea and sickness in pregnancy or undergoing dialysis.
Comparisons of Alzheimer’s disease patients and healthy controls have revealed modest (20%) reductions in the TPP contents of patients’ brains, but dramatic differences in the brain activities of TPP-dependent enzymes (5). It has been suggested that these associations reflect genetic variations in genes encoding portions of one or more of these enzymes. A limited number of small trials have been conducted to test the therapeutic value of thiamin for Alzheimer’s disease; results have been inconclusive.
Limited studies have suggested that patients with Parkinson’s disease may have lower cerebrospinal fluid levels of free thiamin, and reduced activities of thiamin dependent enzymes that are also inhibited by dopamine oxidation products, which are known to be elevated in Parkinson’s disease (6,7).
Diabetic vascular complications appear to involve insufficiencies of thiamin and thiamin dependent enzymes which serve to down regulate intracellular glucose levels, thus avoiding cellular damage. Diabetic subjects have been found to have lower circulating thiamin levels and lower thiamin dependent enzyme activities in erythrocytes than healthy controls (8,9). Supplementation has been shown to prevent diabetic cardiomyopathy and neuropathy and been found effective in preventing vascular dysfunction, oxidative stress, and proteinuria in subjects with type 2 diabetes (10-12). Therefore, it has been suggested that diabetes may appropriately be considered a thiamin-deficient state.
In women with diabetes in pregnancy, maternal thiamin deficiency correlates with abnormally high infant body weight (13). Thiamin deficiency has been implicated in cases of sleep apnoea and sudden infant death syndrome (SIDS). While this relationship is not elucidated, it would appear reasonable to expect thiamin to have a role in maintaining the brainstem function governing automatic respiration.
Widespread thiamin depletion in Cuba was reported in 1992–1993 during an epidemic of optic and peripheral neuropathy that affected some 50,000 people in a population of 11 million (14). A large portion (30–70%) of both the cases and the apparently unaffected population showed signs of low thiamin status. The incidence of new cases subsided with the institution of multivitamin supplementation. Still, it is not clear that thiamin deficiency, while widespread in that population, was the cause of the epidemic of neuropathy.
Thiamin deficiency, in developed society, stems mostly from excessive alcohol intake.
A number of similarities exist between fibromyalgia (FM) and thiamin deficiency. They include irritability, frequent headaches, unusual fatigue, muscle tenderness upon pressure palpitation, muscular weakness, irritable bowel syndrome, and sleep disturbances (14). Studies published in JACN have demonstrated abnormalities of thiamin metabolism in FM (15).
Thiamin deficiency manifests as symptoms of coronary heart failure and, therefore, may worsen existing heart failure. Congestive heart failure patients may be at increased risk for thiamine deficiency as a result of diuretic-induced urine thiamin excretion, disease severity, malnutrition, and advanced age. These authors found increased urinary losses of thiamin were predictive of improved thiamin status and concluded thiamin supplementation may be protective in the clinical setting (16).
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