Which are the consequences if any of a vitamin E deficiency? Is a vitamin E deficiency syndrome in

Fråga: Which are the consequences if any of a vitamin E deficiency? Is a vitamin E deficiency syndrome in man described? What is known on fat malabsorption and vitamin E deficiency especially in connection with cystic fibrosis?

Sammanfattning: "As conclusion we would like to quote from Bieri (19):

""After fifty years of research on the role of vitamin E in health and disease, we know that patients with genetic diseases or congenital defects which cause malabsorption can develop vitamin E deficiency with associated symptoms. These are the only medical conditions where there is a consensus that vitamin E has a proven therapeutic role.

Many other clinical problems for which the vitamin is sometimes prescribed used further study to provide more convincing evidence of efficacy. Healthy persons recieve an adequate intake of vitamin E in a balanced diet that meets other nutritional needs. Use of supplementary vitamin E by such individuals has not been shown to confer any additional health or fitness benefits"". An additional full-text information is available by request."

Svar: MECHANISM OF ACTION. Vitamin E is one of the principal defense mechanisms against oxidizing agents in the body. Tocopherol plays a very important role in the membrane protecting system of free radical scavengers (1-4).

VITAMIN-E DEFICIENCY. Vitamin-E deficiency is very uncommon. One recognized condition is hemolytic anemia in premature babies (1,4). In children with severe congenital vitamin E malabsorption secondary to abetalipoproteinemia and associated steatorrhoea, a neurological deficiency syndrome can be detected after 18 to 24 months (4). In contrast, at least 10 to 20 years of fat malabsorption appear to preceed neurologic symptoms in adults with vitamin E deficiency (5). However in patients with a very severe fat malabsorption, there have been cases reported with clinical symptoms of vitamin-E deficiency, obtained in much shorter time (6-10).

Vitamin E deficiency can be established in many different clinical conditions with chronic malabsorption. In children the most common conditions are congenital cholestatic hepatobiliary diseases, cystic fibrosis (CF), abetalipoproteinemia, congenital liver diseases or biliary atresia. In adults, cystic fibrosis, Crohn´s disease and short bowel syndrome are known causes of vitamin E deficiency (5). It may also occur in acquired intestinal malabsorption (8) and blind loop syndrome (9).

VITAMIN-E DEFICIENCY SYNDROME. The vitamin E deficiency syndrome varies widely and there have been great difficulties to reach a general agreement on its characteristics. Haemolytic anemia in premature infants (11).

The commonest syndrome of vitamin E deficiency is the neurological one (4, 6-10, 12-14). The characteristic abetalipoproteinemia neurological syndrome, with ophthalmoplegia, retinal pigmentary degeneration, spinocerebellar ataxia, peripheral neuropathy and myopathy has been described, also in other vitamin E deficiency states, with similar clinical picture (7,9). The most frequent symptoms are: areflexia, ataxia, impaired position sense, impaired vibration sense, muscle weakness, nystagmus, loss of touch and pain sensation, slurring of speech and dysarthria (4, 6-9, 14).

The retinal changes associated with vitamin E deficiency are described as a pigmentary degeneration similar to retinitis pigmentosa (quoted in 13). The visual symptons reported include diminished night vision, visual field constriction, loss of visual acuity - and pathological electroretinogram and visual -evoked response (6,10,13).

VITAMIN E REPLACEMENT. The normal adult serum levels of tocopherol range from 12-36 umol/L (0.8 to 1.5 mg/dl), and the diet contents vary from 3 to 30 IU (1 mg dl-alpha tocopherylacetate = 1 IU; 1 mg d-alpha-tocopherol = 1.49 IU). Supplementation of fat soluble vitamins including vitamin E is a general recommendation from CF treatment centers (15).

Vitamin E must, however, be administered rationally. In abetalipoproteinemia very large oral doses of about 100 mg/kg/day must be given in order to achieve an adequate vitamin E levels (4). In patients with greatly reduced small- intestinal concentrations of bile salts, who are unable to absorb an oral preparation, intramuscular administration will probably be needed to achieve normal serum concentrations.

Patients with uncomplicated CF could be treated with a soluble oral preparation of alpha-tocopheryl acetate. Normal serum vitamin E concentrations could generally be achieved after one month on a dose of 10 mg/kg/day. Thereafter a lower dose of 200 mg/day (which is considered as DDD (16)) appeared sufficient to maintain concentrations within the normal range (6).

A low serum or plasma selenium concentration per se is not an indication for selenium supplementation in CF, although such has been suggested (cf 17). A contraindiciation for selenium supplementation may exist in patients deficient in both vitamin E and selenium, as it is suggested that selenium toxicity is enhanced in the presence of vitamin E deficiency (cf 17) because toxicity occurs at a lower level of selenium administration.

THERAPEUTIC USE OF VITAMIN-E. In addition to severe malabsorption there are in two clinical situations, where the administration of vitamin E is suggested. In other retrolental fibroplasia which could occur in premature infants exposed to high oxygen partial pressure the administration of vitamin E in the first hours could be of help. Very high doses, 100 mg/kg/day (which achieve serum levels between 1.2 and 4.6 mg/100 ml) are recommended, but could not give a complete protection (18,19). The other clinical situation is the hemolyticalanemia in the premature associated with vitamin E deficiency (18). However the therapeutic effect of vitamin E in these conditions is not convincingly documented according to (19).

ADVERSE DRUG REACTIONS. Very high dose of tocopherol are relatively free of adverse effects. Diarrhoea and intestinal cramps have been reported daily doses of 3200 IU of vitamin E (20). Worsening of hypertension, and reduced intestinal absorption of vitamins A and K have been suggested in a review article (21). The same source (21) quotes that vitamin E supplementation has been associated with suppression of some immune parameters. A high dose of (1 g/day) vitamin E has been reported to induce a hamorrhagic state in a patient taking warfarin and clofibrate (cf 20). This apparently increased effect of the anticoagulant does not seem to have been followed up since the original report in 1974. For most people, doses of 200 to 600 mg alpha-tocopherol daily appear to be innocuous, but we do not have sufficient information over a lifetime to say that such supplements are totally safe (19).

In addition to the use of vitamin E as supplementation in malabsorption states, the compound is also very popular on indications that are not scientifically documented like increase of sexual performance in the man, improvement of peripheral circulation and improvement of general well being. 1 Klinisk kemi. Laurell, 1976, 3rd ed, 124-125 2 Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG: Selenium: biochemical role as a component of glutathione peroxidase. Science 1973; 179: 588-590 3 Mills CF: Biochemical roles of trace elements. In: Nutrition in health and disease and international development. Symposia from the XII international congress of nutrition. 1981, Alan R Liss Inc, New York, p 179-188 4 Muller DPR, Lloyd JK, Wolff OH: Vitamin E and neurological function. Lancet 1983; I: 225-227 5 Sokol RJ: Vitamin E deficiency in adults. Ann Intern Med 1984; 100: 769-770 6 Willison HJ, Muller DPR, Matthews S, Jones S, Kriss A, Stead RJ, Hodson ME, Harding AE: A study of the relationship between neurological function and serum vitamin E concentrations in patients with cystic fibrosis. J Neurol Neurosurg Psychiatry 1985; 48: 1097-1102 7 Bye AME, Muller DPR, Wilson J, Wright VM, Mearns MB: Symptomatic vitamin E deficiency in cystic fibrosis. Arch Dis Child 1985; 60: 162-164 8 Weder B, Meienberg O, Wildi E, Meier C: Neurologic disorder of vitamin E deficiency in acquired intestinal malabsorption. Neurology 1984; 34: 1561-1565 9 Brin MF, Fetell MR, Green PHA, Kayden HJ, Hays AP, Behrens MM, Baker H: Blind loop syndrome, vitamin E malabsorption, and spinocerebellar degeneration. Neurology 1985; 35: 338-342 10 Larsen PD, Mock DM, O´Connor PS: Vitamin E deficiency associated with vision loss and bulbar weakness. Ann Neurol 1985; 18: 725-727 11 Phelps DL: Vitamin E: Where do we stand. Pediatrics 1979; 63: 933-935 12 Stead RJ, Muller DPR, Matthews S, Hodson ME, Batten JC: Effect of abnormal liver function on vitamin E status and supplementation in adults with cystic fibrosis. Gut 1986; 27: 714-718 13 Messenheimer JA, Greenwood RS, Tennison MB, Brickley JJ, Ball CJ: Reversible visual evoked potential abnormalities in vitamin E deficiency. Ann Neurol 1984; 15: 499-501 14 Harrison´s princi