Vitamin neuropathy

Rice bran is the richest natural source of B-complex vitamins. Considerable amounts of thiamin (Bl), riboflavin (B2), niacin (B3), pantothenic acid (B5) and pyridoxin (B6) are available in rice bran (Table 17.1). Thiamin (Bl) is central to carbohydrate metabolism and kreb s cycle function. Niacin (B3) also plays a key role in carbohydrate metabolism for the synthesis of GTF (Glucose Tolerance Factor). As a pre-cursor to NAD (nicotinamide adenine dinucleotide-oxidized form), it is an important metabolite concerned with intracellular energy production. It prevents the depletion of NAD in the pancreatic beta cells. It also promotes healthy cholesterol levels not only by decreasing LDL-C but also by improving HDL-C. It is the safest nutritional approach to normalizing cholesterol levels. Pyridoxine (B6) helps to regulate blood glucose levels, prevents peripheral neuropathy in diabetics and improves the immune function. 

The cause of pruritus is unknown, although several mechanisms have been proposed. Vitamin A is known to accumulate in the skin and serum of patients with CKD, but a definite correlation with pruritus has not been established. Histamine may also play a role in the development of pruritus, which may be linked to mast cell proliferation in patients receiving hemodialysis. Hyperparathyroidism has also been suggested as a contributor to pruritus, despite the fact that serum PTH levels do not correlate with itching. Accumulation of divalent ions, specifically magnesium and aluminum, may also play a role in pruritus in patients with CKD. Other theories that have been proposed include inadequate dialysis, dry skin, peripheral neuropathy, and opiate accumulation.43... 

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... 

Prognosis is more favorable in the pyridoxine-respon-sive patients. Patients who respond to large doses of vitamin B6 (250-500 mg/day for several weeks) have the best prognosis. Efficacy of treatment usually is reflected in a reduction of blood homocystine and methionine to normal or near-normal levels. Since supplementation with pyridoxine can cause a deficiency of folic acid, the latter should be given (2-5 mg daily) at the same time. Any patient receiving pyridoxine should be monitored carefully for any signs of hepatotoxicity and for a peripheral neuropathy (see Ch. 36). 

Much of the toxicological interest in cyanide relating to mammals has focused on its rapid lethal action. However, its most widely distributed toxicologic problems are due to its toxicity from dietary, industrial, and environmental factors (Way 1981, 1984 Gee 1987 Marrs and Ballantyne 1987 Eisler 1991). Chronic exposure to cyanide is correlated with specific human diseases Nigerian nutritional neuropathy, Leber s optical atrophy, retrobulbar neuritis, pernicious anemia, tobacco amblyopia, cretinism, and ataxic tropical neuropathy (Towill etal. 1978 Way 1981 Sprine etal. 1982 Beminger et al. 1989 Ukhun and Dibie 1989). The effects of chronic cyanide intoxication are confounded by various nutritional factors, such as dietary deficiencies of sulfur-containing amino acids, proteins, and water-soluble vitamins (Way 1981). 

Supplemental doses of pyridoxine hydrochloride (vitamin B6), 50 mg/ day, are recommended to prevent the peripheral neuropathy associated with isoniazid administration. 

Common but usually transient side effects are lethargy, incoordination, blurred vision, higher cortical dysfunction, and drowsiness. At concentrations greater than 50 mcg/mL, phenytoin can exacerbate seizures. Chronic side effects include gingival hyperplasia, impaired cognition, hirsutism, vitamin D deficiency, osteomalacia, folic acid deficiency, carbohydrate intolerance, hypothyroidism, and peripheral neuropathy. 

The nervous system is the most sensitive target for cyanide toxicity, partly because of its high metabolic demands. High doses of cyanide can result in death via central nervous system effects, which can cause respiratory arrest. In humans, chronic low-level cyanide exposure through cassava consumption (and possibly through tobacco smoke inhalation) has been associated with tropical neuropathy, tobacco amblyopia, and Leber s hereditary optic atrophy. It has been suggested that defects in the metabolic conversion of cyanide to thiocyanate, as well as nutritional deficiencies of protein and vitamin B12 and other vitamins and minerals may play a role in the development of these disorders (Wilson 1965). 

Vitamin deficiency can cause a megaloblastic anemia of the same type seen in folate deficiency (discussed in Chapter 17). In a patient with megaloblastic anemia, it is important to determine the underlying cause because Bjj defidency, if not corrected, produces a peripheral neuropathy owing to aberrant fatty acid incorporation into the myelin sheets associated with inadequate methylmalonyl CoA mutase activity. Excretion of methylmalonic acid indicates a vitamin Bjj deficiency rather than folate. 

The molecules that constitute vitamin Be are quite safe and there is no established UL. However, the ingestion of industrial doses of pyridoxine, 2-6 g/day for 2 0 months, is known to have caused sensory ataxia and sensory peripheral neuropathy. The senses of touch, temperature, and pain may be altered. Recovery may be slow and incomplete. 

Vitamin Bn deficiency Deficiency, although rare, results in two serious problems megaloblastic anaemia (which is identical to that caused by folate deficiency) and a specific neuropathy called Bi2-associated neuropathy or cobalamin-deficiency-associated neuropathy (previously called, subacute combined degeneration of the cord). A normal healthy adult can survive more than a decade without dietary vitamin B12 without any signs of deficiency since it is synthesised by microorganisms in the colon and then absorbed. However, pernicious anaemia develops fairly rapidly in patients who have a defective vitamin B12 absorption system due to a lack of intrinsic factor. It results in death in 3 days. Minot and Murphy discovered that giving patients liver, which contains the intrinsic factor, and which is lightly cooked to avoid denaturation, cured the anaemia. For this discovery they were awarded the Nobel Prize in Medicine in 1934. 

Isoniazid is bactericidal against growing M. tuberculosis. Its mechanism of action remains unclear. (In the bacterium it is converted to isonicotinic acid, which is membrane impermeable, hence likely to accumulate intracellu-larly.) Isoniazid is rapidly absorbed after oral administration. In the liver, it is inactivated by acetylation, the rate of which is genetically controlled and shows a characteristic distribution in different ethnic groups (fast vs. slow acetylators). Notable adverse effects are peripheral neuropathy, optic neuritis preventable by administration of vitamin Be (pyridoxine) hepatitis, jaundice. 

Myopathy and neuropathy Colchicine myoneuropathy appears to be a common cause of weakness in patients on standard therapy who have elevated plasma levels caused by altered renal function. It is often unrecognized and misdiagnosed as polymyositis or uremic neuropathy. Proximal weakness and elevated serum creatine kinase are generally present, and resolve in 3 to 4 weeks following drug withdrawal. Maiabsorption of vitamin B-f2- Colchicine induces reversible malabsorption of vitamin B-12, apparently by altering the function of ileal mucosa. 

However, vitamin B12 also plays a role in the conversion of methionine to S-adenosylmethionine which could explain the neuropathy that results from vitamin B12 deficiency. 

CNS toxicity occurs because isoniazid has structural similarities to pyridoxine (vitamin Be) and can inhibit its actions. This toxicity is dose-related and more common in slow acetylators. Manifestations include peripheral neuropathy, optic neuritis, ataxia, psychosis and seizures. The administration of pyridoxine to patients receiving INH does not interfere with the tuberculostatic action of INH but it prevents and can even reverse neuritis. Hematological effects include anaemia which is also responsive to pyridoxine. In some 20% of patients antinuclear antibodies can be detected but only in a minority of these patients drug-induced lupus erythematosus becomes manifest. 

Pyridoxine is indicated in vitamin B deficiency, for the treatment of some pyridoxine responsive anemia s and for isoniazid-induced neuropathy. It may relieve symptoms of pellagra when niacin fails. Long-term administration of large doses may produce neurotoxicity manifesting itself in progressive peripheral sensory neuropathy. 

Severe cyanocobalamin (vitamin B12) deficiency results in pernicious anemia that is characterized by megaloblastic anemia and neuropathies. The symptoms of this deficiency can be masked by high intake of folate. Vitamin B12 is recycled by an effective enterohep-atic circulation and thus has a very long half-hfe. Absorption of vitamin B12 from the gastrointestinal tract requires the presence of gastric intrinsic factor. This factor binds to the vitamin, forming a complex that... 

The effects of most vitamin B overdoses have not been documented, although large dosages of pyridoxine have been reported to cause peripheral neuropathies. Ataxia and numbness of the hands and feet and impairment of the senses of pain, touch, and temperature may result. Excessive niacin intake may result in flushing, pruritus, and gastrointestinal disturbances. These symptoms are due to niacin s ability to cause the release of histamine. Large dosages of niacin can result in hepatic toxicity. 

As well as being implicated as a hepatotoxin, the antitubercular drug isoniazid may also cause peripheral neuropathy with chronic use. In practice, this can be avoided by the concomitant administration of vitamin B6 (pyridoxine). 

Vitamin B6 (pyridoxine, pyridoxamine, and pyridoxal) has the active form, pyridoxal phosphate. It functions as a cofactor for enzymes, particularly in amino acid metabolism. Deficiency of this vitamin is rare, but causes glossitis and neuropathy. The deficiency can be induced by isoniazid, which causes sensory neuropathy at high doses. 

Electroencephalographic abnormalities associated with vitamin B therapy have been reported (SEDA-15, 412 18). Tingling of the fingertips, faintness, and dizziness have been observed. Peripheral neuropathy has been reported (19). Tingling in the orofacial region has been attributed to a neuropathic effect, but this could have been due to vasodilatation. 

A neuropathy caused by clioquinol (iodochlorohydroxyquin, chinoform) and enhanced by the formation of a clioquinol ferric chelate which initiates lipid peroxidation, leads to complete degeneration of retinal neuroblasts within a day. Vitamin E has a potent protective action against the effects of the chelate [75]. Peroxidative damage to DNA in rat brain, induced by methyl ethyl ketone peroxide, a potent initiator of lipid peroxidation, was inhibited by addition of vitamin E to the diet of rats [76]. 

Vitamin B12 is a biologically active corrinoid, a group of cobalt-containing compounds with macrocyclic pyrrol rings. Vitamin B12 functions as a cofactor for two enzymes, methionine synthase and L-methylmalonyl coenzyme A (CoA) mutase. Methionine synthase requires methylcobalamin for the methyl transfer from methyltetrahydrofolate to homocysteine to form methionine tetrahy-drofolate. L-methylmalonyl-CoA mutase requires adenosylcobalamin to convert L-methylmalonyl-CoA to succinyl-CoA in an isomerization reaction. An inadequate supply of vitamin B12 results in neuropathy, megaloblastic anemia, and gastrointestinal symptoms (Baik and Russell, 1999). 

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