Thiamine, alcoholism

Cessation of prolonged heavy alcohol abuse may be followed by alcohol withdrawal or life-threatening alcohol withdrawal delirium. Typical withdrawal symptoms are autonomic hyperactivity, increased hand tremor, insomnia and anxiety, and are treated with benzodizepines and thiamine. Alcoholism is the most common cause of thiamine deficiency and can lead in its extreme form to the Wernicke s syndrome that can be effectively treated by high doses of thiamine. 

The thiazole and pyrimidine heterocycles (33 and 32), as well as thiamin alcohol, can he salvaged from the bacterial growth medium and the kinases required for conversion of these precursors to biosynthetic intermediates have all been characterized (Figure 1HMP-P kinase catalyzes the iterative phosphorylation of... 

The thiamin (vitamin BO molecule contains a quaternary ammonium functionality and is thus badly absorbed. In healthy patients the necessary amounts of thiamin are absorbed thanks to an active transport mechanism coupled with ATP consumption. However, these mechanisms are rapidly saturable and easily inhibited, especially by chronic alcoholic consumption. As a consequence of the insufficient absorption of thiamin, alcoholism often entails Wernicke s encephalopathy (neurological disorders such as nystagmus, ocular motor nerve paralysis, memory losses, disorientation). The design of lipophilic prodrugs, able to reach the CNS by passive diffusion was then undertaken compounds like (a) and (b) result from lipophilic disulphide derivation of the open ring thiolate anion corresponding to thiamine (Fig. 33.39). 

Therapy. Thiamin is necessary for decarboxylation of alpha keto acid therefore, the requirement is proportional to the percentage of carbohydrate in the diet, approximately 0.5 mg/1,000 Kcal (RDA, 1980). The average adult daily intake is close to 0.8 mg, which suggests that some of the population might be marginal in this nutrient. Fortunately, fats and protein have a thiamin-sparing effect. Thiamin is not stored and various outside "stresses such as fever, hyperthyrodism, and trauma seem to influence the need for thiamin. Alcoholics with inadequate diets are particularly susceptible to thiamin deficiency. 

Thiamine forms the expected derivatives of the thia zole alcohol function, such as carboxyUc and phosphate esters. Eew reactions at the pyrimidine 4-amino function have been reported. Most of the usual conditions used for formation of amides, for example, lead to destmction of the thiazolium ring. 

O Nucleophilic addition of thiamin diphosphate (TPP) ylide to pyruvate gives an alcohol addition product. 

Fermenting baker s yeast also catalyzes the 1,4-addition of a formal trifluoroethanol-d1-synthon to a,/i-unsaturated aldehydes, to give optically active l,l,l-trifluoro-2-hydroxy-5-alka-nones52. Presumably, the mechanism involves oxidation of the alcohol to the corresponding aldehyde followed by an umpolung step with thiamine pyrophosphate and Michael addition to the a,/i-unsaturated aldehyde. For example, l,l,l-trifluoro-2-hydroxy-5-hexanone (yield 26%, ee 93%) is thus obtained from trifluoroethanol and l-bnten-3-one. 

Beri-beri or clinically manifest thiamin deficiency exists in several subforms infantile beri-beri and adult beri-beri. Infantile beri-beri occurs in exclusively breastfed infants of thiamin-deficient mothers. Adults can develop different forms of the disease, depending on their constitution, environmental conditions, the relative contribution of other nutrients to the diet as well as the duration and severity of deficiency. First of all, there is a so called dry or atrophic (paralytic or nervous) form, including peripheral degenerative polyneuropathy, muscle weakness and paralysis. Second, a wet or exudative (cardiac) form exists. In this form, typical symptoms are lung and peripheral oedema as well as ascites. Finally, there is a cerebral form, that can occur as Wernicke encephalopathy or Korsakoff psychosis. Tli is latter form mostly affects chronic alcoholics with severe thiamin deficiency. 

Wernicke s syndrome is a serious consequence of alcoholism and thiamine (vitamin Bx) deficiency. Certain characteristic signs of this disease, notably ophtalmoplegia, nystagmus, and ataxia, respond rapidly to the administration of thiamine but to no other-vitamin. Wernicke s syndrome may be accompanied by an acute global confusional state that may also respond to thiamine. Left untreated, Wernicke s syndrome frequently leads to a chronic disorder in which learning and memory are strongly impaired. This so-called Korsakoff s psychosis is characterized by confabulation, and is less likely to be reversible once established. 

The identification of co-occurring medical problems is an important element in detoxification (Naranjo and Sellers 1986). Good supportive care and treatment of concurrent illness, including fluid and electrolyte repletion, are essential (Naranjo and Sellers 1986). Administration of thiamine (50—100 mg/day po or im) and multivitamins is a low-cost, low-risk intervention for the prophylaxis and treatment of alcohol-related neurological disturbances. 

Thiamin deficiency can result in three distinct syndromes a chronic peripheral neuritis, beriberi, which may or may not be associated with heart ilure and edema acute pernicious (fulminating) beriberi (shoshin beriberi), in which heart failure and metabolic abnormalities predominate, without peripheral neuritis and Wernicke s encephalopathy with KorsakofPs psychosis, which is associated especially with alcohol and dmg abuse. The central role of thiamin diphosphate in... 

True. Excessive alcohol use can lead to serious damage to mental health. Depression, anxiety, delusions and negative changes in personality can occur. Korsakoff s psychosis occurs in some excessive users of alcohol. This form of dementia results in disorientation, loss of memory and lowered intellectual abilities. It is reversible in some sufferers through the administration of thiamine (vitamin Bj. 

Thiamine Vitamin B, a deficiency of which in alcoholics can lead to Wernicke-Korsakolf s syndrome. 

Thiamine deficiency results in early decreases in activity of the mitochondrial enzyme a-ketoglutarate dehydrogenase in brain. Wernicke s encephalopathy, also known as the Wernicke-Korsakoff syndrome is a neuropsychiatric disorder characterized by ophthalmoplegia, ataxia and memory loss. Wernicke s encephalopathy is encountered in chronic alcoholism, in patients with HIV-AIDS and in other disorders associated with grossly impaired nutritional status. The condition results from thiamine deficiency. 

Neuropathy can result from deficiency of vitamins or hormones. Alcoholics often obtain a large proportion of their caloric needs from ethanol, and hence become thiamine-deficient. Alcoholic neuropathy results from a combination of thiamine deficiency, which impairs... 

Koike, H., Iijima, M., Sugiura, M. et al. Alcoholic neuropathy is clinicopathologically distinct from thiamine-deficiency neuropathy. Ann. Neurol. 54 19-29,2003. 

Classic beri-beri, rarely seen in the United States and Europe, except in alcoholism (P4), is endemic in the Far East because of the prevalent diet of decorticated rice (F6). It occurs in two forms wet beri-beri, characterized by edema and cardiovascular symptoms (G6), and dry beri-beri with peripheral neuritis, paralysis, and atrophy of the muscles. Conditions which may predispose to deficiency by increasing thiamine requirements are pregnancy (see section 2.4), and lactation, hyperthyroidism, malignant disease, febrile conditions, increased muscular activity, high carbohydrate diets, and parenteral administration of glucose solutions. A constant supply of thiamine is required for optimal nutrition because storage in the liver and elsewhere is limited. Thiamine is synthesized by bacteria in the intestinal tract of various animals, but this is not a dependable source for man. 

The way in which thiamine participated in the oxidation of pyruvate became clearer when Lohmann and Schuster (1937) showed vitamin Bj to be present intracellularly as thiamine pyrophosphate. In yeast, decarboxylation of pyruvate yielded ethanal which was reduced by alcohol dehydrogenase to give ethanol. A cofactor was needed for this decarboxylation, co-carboxylase. Like the cofactor needed in animal cells for the decarboxylation of pyruvate, cocarboxylase was found to be identical to thiamine pyrophosphate. Vitamin Bj thus became the first vitamin whose intracellular function as a coenzyme had been established in vitro. Another aphorism therefore arose about vitamins—B vitamins are (parts of) coenzymes—an idea that was to be completely confirmed. 

Thiamine (Bj) Pyruvate dehydrogenase PDH MCC alcoholism (alcohol interferes... 

Thiamine deficiency is commonly seen in alcoholics, who may develop a complex of symptoms associated with Wernicke peripheral neuropathy and Korsakoff psychosis. Alcohol interferes with thiamine absorption from the intestine. Symptoms include ... 

Delirium tremens (the D.T.s ) resulting from alcohol withdrawal is slightly different in that it is usually preceded by the shakes, convulsions and occasionally by alcoholic hallucinosis - characterized by accusatory auditory hallucinations. As observed 60 years ago by Maurice Victor, an expert on alcohol problems, delirium tremens usually does not appear until day 3 or 4 following abrupt withdrawal from alcohol. The patient is generally malnourished and grossly deficient in vitamin Bj (thiamine) as the result of a diet consisting of little but alcohol. This deficiency ftirther compromises mental function. 

When the alcoholic first presents for treatment, his/her nutritional status should be fully assessed. Vitamin supplementation should always be a component of this treatment. In the emergency room setting, the alcoholic patient usually receives intravenous fluids containing magnesium, thiamine, and multivitamin supplements. The yellow-colored fluid is commonly called a banana bag or rally pack. A daily... 

Nutrient supplementation during alcohol detoxification includes thiamine, magnesium sulfate, folic acid, and a multivitamin. During the rehabilitation and continuing care stages of treatment for alcohol dependence, nutrient supplementation includes thiamine and a multivitamin. 

Substance-Induced Dementias. Substances of abuse can also cause dementia. The most common is alcohol-related dementia. Chronic alcoholism leads to dementia in several ways. The poor diet of the alcoholic causes a deficiency of certain essential nutrients such as thiamine. The alcoholic often suffers recurrent head injuries from falls or altercations. Alcohol-induced liver failure can expose the brain to toxic injury. Finally, the direct toxic effects of alcohol itself on the brain can lead to dementia. In addition to alcohol, the abuse of inhalants such as paint thinner and... 

Nutritional Deficiency-Related Dementias. We have already mentioned that chronic alcoholics are subject to thiamine deficiency that can cause dementia. It usually occurs only after heavy, prolonged abuse of alcohol. In developed countries, the other key nutritional concern is vitamin deficiency. Vitamin deficiency can surprisingly strike even those with a healthy diet. Such people are missing a vital protein, intrinsic factor, which would enable them to absorb it from their digestive tract. 

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