Thiamine deficiency in alcoholics

Thiamin deficiency in alcoholics may be caused by decreased intake, reduced absorption, and impaired ability to use ihe absorbed vitamin. The ataxia and ocular symptoms associated with the deficiency in alcoholics are known as Wernicke s disease. Vitamin therapy can provide relief from nystagmus within a few hours of treatment and from ataxia within several weeks. The treatment of alcoholics also involves the supply of other nutrients lacking in the diet, such as folate, vitamin B12, and protein. Left imtreated, patients suffering from Wernicke s disease continue to develop Korsakoff s psychosis, which involves amnesia and confusion. Only about 25% of patients with Korsakoff s psychosis can be completely cured by thiamin treatment, which must be continued for a few weeks or months. The two conditions just described constitute the Wemicke-Korsakoff syndrome. The S5mdrome was named after two researchers. Karl Wernicke, a German, noted impaired or paralyzed eye movements and imstable walking and disorientation in his patients, most of whom were alcoholics. Polyneuropathy, a weakness of the hands, calves, and feet, was also noted. Sergei Korsakoff, a Russian, observed amnesia and confusion and an inability to learn new names or tasks in alcoholic patients. 

The incidence of thiamine deficiency in alcoholics is 30-80% (Homewood and Bond, 1999). Factors that promote thiamine deficiency in alcoholics include poor thiamine intake, decreased activation of thiamine to thiamine pyrophosphate(TPP), decreased hepatic storage, decreased intestinal thiamine transport and impairment of thiamine absorption (see Table 14.3) (Breen et al, 1985 Hoyumpa, 1980). Although thiamine is stored in various sites, including skeletal muscles, heart, kidneys and brain, the Uver remains the main storage site. Due to the reasons cited above, hepatic thiamine content may be reduced by 73% in patients with severe, chronic alcoholic liver disease. In addition, ethanol has been shown to promote thiamine release from the liver (Hoyumpa, 1980). 

Martin, P.R., Singleton, C.K., and Hiller-Sturmhofel, S., 2003. The role of thiamine deficiency in alcoholic brain disease. Alcohol Research Health. 27 134-142. 

Thiamin is a water-soluble vitamin. The RDA of thiamin for the adult man is 1.5 mg. The vitamin is present in a variety of foods of plant and aiumal origin, as well as in yeast. The populations most at risk of developing a deficiency are chronic alcoholics in Western countries and those with an overdeptendence on polished rice as a staple in underdeveloped nations. The consumption of large amounts of raw seafood can also induce the deficiency. Thiamin deficiency in humans is called beriberi. The disease occurs in a variety of forms and causes different problems in infants, adults, and alcoholics. 

Many alcoholics such as Al Martini develop thiamine deficiency because alcohol inhibits the transport of thiamine through the intestinal mucosal cells. In the body, thiamine is converted to thiamine pyrophosphate (TPP). TPP acts as a coenzyme in the decarboxylation of a-keto acids such as pyruvate and a-ketoglutarate (see Fig. 8.11) and in the utilization of pentose phosphates in the pentose phosphate pathway. As a result of thiamine deficiency, the oxidation of a-keto acids is impaired. Dysfunction occurs in the central and peripheral nervous system, the cardiovascular system, and other organs. 

Wernicke Korsakoff syndrome (WKS) is the neurological disorder most clearly linked to thiamine deficiency in humans. WK develops in a subset of chronic alcoholics, who are vitamin deficient because so many calories are consumed as alcohol instead of normal diet, and a diet rich in carbohydrates increases the metabolic demand for thiamine. Thiamine dependent enzymes were diminished in the brains of patients who died with WKS, but not in alcoholic controls (Butterworth et al., 1993). Transketolase in fibroblasts from those patients who develop WKS syndrome binds TPP more avidly than the control lines. The Km was nearly ten times higher in patients with WKS. Thus, these patients have an abnormahty of transketolase that would be clinically unimportant if the diet was adequate (Blass and Gibson, 1977, 1979). The latter demonstrate a predisposing biochemical mutation to a neurological diseases that is only revealed by inadequate diet. 

Table 14.3 Possible causes of thiamine deficiency in chronic alcoholism...

Clinical manifestations of thiamine deficiency develop in only a small fraction of alcoholics and other chronically malnourished people. Do some patients have an inborn predisposition to developing neurologic disease with thiamine deficiency Four alcoholics with the disease were shown to have a cellular defect in the enzyme transketolase (Blass and Gibson, 1977). The defective enzyme bound thiamine pyrophosphate with only 5-10% of the normal avidity. Presumably, this represents a genetically determined structural mutation in transketolase. When diet is adequate, the genetic abnormality would be clinically silent, but with the stress of marginal thiamine intake, affected individuals would more readily develop disease. 

Strangely, cellular ThDP levels are 2-3 times lower in humans than in rodents, and this is also true for the brain (Gangolf et al. 2010a). This is probably linked to very low circulating thiamin levels in humans, possibly because intestinal thiamin absorption is less efficient. This would explain the higher sensitivity of humans to thiamin deficiency, in particular in association with alcohol consumption partial inhibition of intestinal thiamin uptake by alcohol would be sufficient to critically affect thiamin absorption. 

Levy, S., Herve, C., Delacoux, E., and Erlinger, S., 2002. Thiamine deficiency in hepatitis C virus and alcohol-related liver diseases. Digestive Diseases and Sciences. 47 543-548. 

The majority of cases of WE involve a combination of the effects of both alcohol and thiamine deficiency in the resulting neuropathology. 

Wernicke s encephalopathy. This is most frequent clinical manifestation of thiamine deficiency in developed countries. It is frequently associated with alcoholism and other conditions impairing nutrition. This neuropsychiatric disorder is characterized by eye muscle paralysis, abnormal posture and gait, and impaired cognitive functions. Progressive deterioration of WE patients ends with KorsakofFs psychosis with manifestation of amnesia, stupor and loss of conceptual functions. 

Sgouros, X., Baines, M., Bloor, R.N., McAuley, R., Ogrmdipe, L., and Willmott, S., 2004. Evaluation of a clinical screening instrument to identify states of thiamine deficiency in inpatients with severe alcohol dependence syndrome. Alcohol and Alcoholism. 39 227-232. 

Apart from some conflicting therapeutic cltiims there is, however, little if any, convincing evidence of an associated thiamine deficiency in this condition. Goodhart and Sinclair [28] found that the levels of cocarboxylase in the blood were normal in four out of the five patients studied by them, the fifth patient, in whom a low level was found, being also an alcohol addict. Martin [29] carried out pyruvate tolerance tests following the intravenous injection of pyruvate to a series of diabetic subjects and concluded that pyruvate metabolism was normal. Thompson, Butterfield and Kelsey-Fry [30] reported on the blood pyruvate levels in glucose-insulin tests performed on a series of diabetic patients with and without neuropathy, and found that the levels were no higher in patients with neuropathy than in the other diabetics. 

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. 

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. 

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... 

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. 

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. 

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. 

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. 

Thiamine deficiency may also develop In alcoholics due to poor nutrition and poor absorption of thiamine In the gastrointestinal tract. 

In chronic alcoholics, thiamine deficiency may manifest as Wernicke-Korsakoff syndrome, which Is characterized by a constellation of unusual neurologic disturbances. Including amnesia, apathy, and nystagmus. 

Inadequate nutrition and conditions which are complicated by malabsorption may lead to thiamine deficiency. Beriberi, a diet-deficiency disease, is especially prevalent in those parts of the East where the diet consists mainly of polished rice. The disease is characterized by neuritis but may also lead to serious heart failure. Recovery is prompt when adequate amounts of vitamin B1 are restored to the diet. Severe deficiency as can occur in alcoholics may lead to Wernicke s encephalopathy, often accompanied by Korsakoff s syndrome. Care should be taken with intravenous substitution with thiamine in these cases to prevent serious complications like vascular collapse with hypotension, respiratory distress or an-gioedema. 

Severe thiamine vitamin Bf) deficiency results in beriberi. The symptoms can include growth retardation, muscular weakness, apathy, edema, and heart failure. Neurological symptoms, such as personality changes and mental deterioration, also may be present in severe cases. Because of the role played by thiamine in metabolic processes in all cells, a mild deficiency may occur when energy needs are increased. Since thiamine is widely distributed in food, beriberi is rare except in communities existing on a single staple cereal food. The disease does occur with some frequency in alcoholics, whose poor diet may lead to an inadequate daily intake of thiamine. 

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