A 41-yr-old woman with primary biliary cirrhosis developed weakness and wasting in proximal muscles, areflexia, and decreased proprioceptive and vibratory sensation. Investigations revealed law serum levels of vitamin E and
electromyographic and muscle biopsy changes consistent with a neuropathy. Sural nerve histology demonstrated axonal dystrophy with patchy demyelination. These features closely resemble a neurologic syndrome associated with chronic
cholestatic liver disease and vitamin E deficiency in children. Adults with
chronic cholestasis may also be susceptible to neurologic damage from prolonged malabsorption of vitamin E.

We describe a 14-year-old boy who was severely debilitated by the neurological
syndrome associated with vitamin E deficiency secondary to chronic cholestatic
liver disease. In addition to the usual neurological deficits described with
this deficiency, the patient had severe bulbar weakness and vision loss which we attribute to the degree and duration of his vitamin E deficiency. Vitamin A
deficiency may have contributed to his visual disturbance. Early recognition of
vitamin E deficiency is important, as the neurological and visual disorders
which result are treatable.

Early administration of vitamin E to low birth weight (less than 1500 g) infants
results in alleviation of the symptoms of retinopathy of prematurity and a
lowered incidence of intraventricular hemorrhage. If vitamin E is given to
children with cholestatic liver disease (orally or parenterally) before 3 years
of age, neurological symptoms such as areflexia, ataxia, and sensory neuropathy are prevented or reversed. Restitution of neurological function is more limited in children ages 5-17 years even after prolonged therapy. Vitamin E is also useful in prevention of neuropathy and retinopathy associated with
abetalipoproteinemia and cystic fibrosis. Blood levels of tocopherol are often
low in subjects with hemolytic anemias. Administration of vitamin E to
G-6-P-D-deficient subjects increased hemoglobin levels, and decreased the number of irreversibly sickled cells in sickle-cell anemia subjects. Most trials have indicated that administration of vitamin E for 6 months or more to subjects with intermittent claudication results in longer walking distance and improved blood flow. Vitamin E reduces platelet aggregation, platelet adhesion to collagen, and platelet thromboxane production. Prostacyclin production is generally enhanced. The significance of these effects to thrombotic diseases. Epidemiological studies have indicated that subjects with higher blood levels of vitamin E have lower risk of death from ischemic heart disease and cancer, a lower risk of breast cancer, and a lower incidence of infections.

A well-defined degenerative neurological condition has been associated with
cholestatic liver disease in children. This syndrome, heralded by gait and limb
ataxia, areflexia, and proprioceptive and vibratory sensory loss, has also been
observed in abetalipoproteinemia (Bassen-Kornzweig syndrome), cystic fibrosis,
and intestinal malabsorption states. A significant body of evidence suggests
that vitamin E (alpha-tocopherol) deficiency is in large part responsible for
this condition. In this article, a patient manifesting this syndrome is
reported, and the current status of the vitamin E deficiency state is reviewed.

A case of fatal familial intrahepatic cholestasis (Byler disease) developed a
neuromuscular syndrome similar to that in experimental vitamin E deficiency and
abetalipoproteinemia, and died of hepatic and cardiac failure. Serum vitamin E
level was extremely low. Autopsy revealed intrahepatic cholestatic cirrhosis
without obliterative lesions in the bile duct system and marked splenomegaly
with splenoma-like nodules. The other pathological lesions were considered to be due to chronic vitamin E deficiency as follows:1. Mitochondrial changes
especially of the hepatocyte and cardiac muscle. 2. Cardiomyopathy. 3. Myopathy. 4. Vasculopathy. 5. Systemic lipofuscinosis. 6. Lesions of the reproductive and endocrine organs. 7. Kyphoscoliosis and pes cavus. 8. Systemic neuroaxonal dystrophy with peripheral neuropathy.

A progressive neurologic syndrome developed in six children with longstanding
cholestatic liver disease. The neurologic abnormalities included areflexia, gait
disturbance, decreased proprioceptive and vibratory sensation, and paresis of
gaze. Serum vitamin E concentrations were uniformly low. Neuropathological
studies carried out in two of the three fatal cases revealed degeneration of the
posterior column, selective loss of large-caliber, myelinated axons in
peripheral nerve, and spheroids in the gracile and cuneate nuclei. These lesions
are similar to those found in animals with experimentally induced vitamin E
deficiency. We therefore speculate that the neurologic syndrome in these
children may be the result of chronic vitamin E malabsorption.

Several uncertainties remain with respect to the role of intake of fat and/or
total energy in the aetiology of cancer of the colon-rectum. Between 1992 and
1996, 1953 subjects with cancer of the colon-rectum (median age = 62 years) and 4154 hospital controls were interviewed in six Italian areas. The validated
food-frequency questionnaire included questions on 78 foods and recipes, and
specific questions on individual fat intake pattern. Significant trends of
increasing colorectal cancer risk with increasing intake emerged for bread and
pasta, cakes and desserts, and refined sugar. Most vegetables, including pulses, were inversely associated with cancer of the colon and rectum. High fruit intake was associated only with a reduction of rectal cancer. Total energy intake was directly associated with colorectal cancer risk. Among macronutrients, a high intake of starch and saturated fat seemed to lead to an increased risk of
cancer. High intakes of polyunsaturated fatty acids (chiefly derived from olive
oil and seed oils) showed a marginal inverse association with colorectal cancer
risk. Among micronutrients, beta-carotene, vitamin E and calcium showed the most consistent inverse associations. An excess of energy intake, particularly from refined bread and pasta, can be an unfavourable feature of the Mediterranean diet with respect to colorectal cancer risk, especially in the presence of sedentary life.

BACKGROUND: Higher blood levels of alpha-tocopherol, the predominant form of vitamin E, have been associated in some studies with a reduced risk of lung
cancer, but other studies have yielded conflicting results. To clarify this
association, we examined the relationship between prospectively collected serum alpha-tocopherol and lung cancer in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study cohort. METHODS: The ATBC Study was a randomized, clinical trial of 29 133 white male smokers from Finland who were 50-69 years old and who had received alpha-tocopherol (50 mg), beta-carotene (20 mg), both, or neither daily for 5-8 years. Data regarding medical histories, smoking, and dietary factors were obtained at study entry, as was a serum specimen for baseline alpha-tocopherol determination. alpha-Tocopherol measurements were available for 29 102 of the men, among whom 1144 incident cases of lung cancer were diagnosed during a median observation period of 7.7 years. The association between alpha-tocopherol and lung cancer was evaluated with the use of multivariate proportional hazards regression. RESULTS: A 19% reduction in lung cancer incidence was observed in the highest versus lowest quintile of serum alpha-tocopherol (relative risk = 0.81; 95% confidence interval = 0. 67-0.97). There was a stronger inverse association among younger men (<60 years), among men with less cumulative tobacco exposure (<40 years of smoking), and possibly among men receiving alpha-tocopherol supplementation. CONCLUSIONS: In the ATBC Study cohort, higher serum alpha-tocopherol status is associated with lower lung cancer risk; this relationship appears stronger among younger persons and among those with less cumulative smoke exposure. These findings suggest that high levels of alpha-tocopherol, if present during the early critical stages of tumorigenesis, may inhibit lung cancer development.

In contrast to the decreasing trends observed in most countries, gastric-cancer
mortality has remained at about the same level in Mexico throughout the last 40
years. As part of a study carried out in the metropolitan area of Mexico City,
an assessment of nutrient intake and gastric cancer is presented here. The study population comprised 220 cases of gastric cancer and 752 population-based controls. Our results showed 70 to 80% reduction in the risk of developing this tumor, associated with the intake of polyunsaturated fat, fiber and vitamin E; and this effect was independent of the histological type of the tumor (i.e., intestinal or dif use). On the other hand, an increased risk of gastric cancer was related to the consumption of saturated fat (OR(Q4vs.Q1) = 4.37, 95% CI 1.89-10.12) and, cholesterol (OR(Q4vs.Q1) = 2.39, 95% CI 1.23-4.64), but such effects were restricted to the intestinal type of gastric cancer. In the whole study population, mono-unsaturated fat intake increased the risk for gastric cancer, and a marginally significant increasing trend was observed for protein consumption. The findings from this study add information about the role of specific nutrients in the etiology of gastric cancer. Copyright 1999 Wiley-Liss,
Inc.

To examine the protective role of dietary antioxidants (carotenoids, vitamin C,
vitamin E, glutathione, and flavonoids) in lung cancer risk, a case-control
study involving 541 cases of lung cancer and 540 hospitalized controls was
carried out in Uruguay. The relevant variables were energy adjusted using the
residuals method and then categorized in quartiles. Adjusted odds ratios (ORs)
for antioxidants were calculated through unconditional logistic regression. With
the exception of lycopene and vitamin C, the remaining antioxidants were
associated with significant reductions in risk of lung cancer. Of particular
interest was the inverse association between dietary glutathione and lung cancer [OR of quartile with highest intake compared with lowest quartile = 0.42, 95% confidence interval (CI) = 0.27-0.63]. Also, carotenoids and vitamin E were
associated with significant reductions in risk of lung cancer (OR = 0.43, 95% CI
= 0.29-0.64 for total carotenoids and OR = 0.50, 95% CI = 0.39-0.85 for vitamin
E). A joint effect for high vs. low intakes of beta-carotene and glutathione was
associated with a significant reduction in risk (OR = 0.32, 95% CI = 0.22-0.46).
It could be concluded that dietary antioxidants are associated with a
significant protective effect in lung carcinogenesis and that the inverse
association for glutathione persisted after controlling for total vegetables and
fruits.