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Mechanisms of vitamin deficiency in chronic alcohol misusers and the development of the Wernicke-Korsakoff syndrome.

The classic signs of vitamin deficiency only occur in states of extreme depletion and are unreliable indicators for early treatment or prophylaxis of alcoholic patients at risk. Post-mortem findings demonstrate that thiamine (vitamin B1) deficiency sufficient to cause irreversible brain damage is not diagnosed ante mortem in 80-90% of these patients. The causes of vitamin deficiency are reviewed with special attention to the inhibition of oral thiamine hydrochloride absorption in man caused by malnutrition present in alcoholic patients or by the direct effects of ethanol on intestinal transport. As the condition of the patient misusing alcohol progresses, damage to brain, liver, gastrointestinal tract, and pancreas continue (with other factors discussed) to further compromise the patient. Decreased intake, malabsorption, reduced storage, and impaired utilization further reduce the chances of unaided recovery. Failure of large oral doses of thiamine hydrochloride to provide an effective treatment for Wernicke's encephalopathy emphasizes the need for adequate and rapid replacement of depleted brain thiamine levels by repeated parenteral therapy in adequate doses.

Alcoholism↗

Nutritional factors and Alzheimer's disease.

Nutritional factors are integrally linked with Alzheimer's disease (AD). Although AD patients have no changes in energy metabolism, fluctuations in weight are fairly common. The potential role of vitamin B(12) and folate, with the production of hyperhomocysteinemia, in the pathophysiology of AD is explored. The role of free-radical damage in AD is discussed. It is stressed that alterations in dietary lipids may play an important role in cognitive defects in AD secondary to their effects on neuronal membrane lipids. More research is needed on the role of nutrition in the ongoing development of cognitive changes in AD.

Aged↗

Relation between vitamin D, physical performance, and disability in elderly persons.

BACKGROUND: The aim of this study was to evaluate the relationships between vitamin D, functional status, and disability in a sample of elderly, community-dwelling subjects. METHODS: Serum values of 25-hydroxyvitamin D (25[OH] D) and albumin were determined in all participants. Anthropometric measures were obtained, and body composition was assessed using dual-energy x-ray absorptiometry. Arm and leg isometric strength was tested. Reported disability was evaluated using a modified version of the Activities of Daily Living Scale and physical performance with the 6-minute walking test and two items of the Short Form 36 Health Survey Questionnaire (SF-36). RESULTS: A significantly higher prevalence of hypovitaminosis D, defined as level of 25(OH)D < 37.5 nmol/l, was observed in women than in men (55.4% and 35.1%, respectively; p <.001). In women, 25(OH)D was significantly associated with muscular strength and levels of physical function as assessed by SF-36. After adjusting for body mass index, albumin, appendicular fat-free mass, and season, muscle strength was still significantly lower in women with hypovitaminosis D than in those without. Women with reported disability showed significantly lower 25(OH)D values than those without. No relationship between muscular strength, physical function, or reported disability and 25(OH)D was found in men. CONCLUSIONS: In community-dwelling elderly women, 25(OH)D is related to muscular function and reported disability. Because of the high prevalence of hypovitaminosis D in the elderly population, this association seems to be clinically relevant.

Aged↗

Impaired immunity in vitamin A-deficient mice.

Vitamin A deficiency was produced in mice and was used to investigate the role of vitamin A in immune function. Cellular immunity, as measured by delayed-type hypersensitivity, diminished in early deficiency before weight and appetite changes occurred and declined further as the deficiency progressed. Humoral immunity, as measured by serum immunoglobulin M (IgM) responses to a protein antigen (hemocyanin), also declined. The kinetics of antibody production were unaffected by the deficiency. The T-cell number remained unchanged, but B-cell and macrophage numbers were increased in vitamin A--deficient mice. Surface expression of membrane glycoproteins (Thy-1, Lyt-1, Lyt-2, L3T4, IgM, Mac-1) was unchanged by the deficiency, as were lymphocyte numbers and distribution. The results suggest that vitamin A deficiency is associated with a functional immune system defect.

Animals↗

Vitamin A deficiency exacerbates methotrexate-induced jejunal injury in rats.

Two studies were conducted to investigate whether vitamin A-deficient rats were more susceptible to intestinal injury caused by methotrexate (MTX), since vitamin A deficiency alone causes only mild changes to jejunal structure and function. Weanling male rats were fed a vitamin A-deficient diet (-VA) for 40-42 d and compared to rats either pair-fed (PF) or with free access (+VA) to the same diet. Drinking water of PF and +VA rats was supplemented with 37.5 microg (Study 1) or 75 microg (Study 2) vitamin A (Rovimix A 500W)/d. Rats in each group received MTX (-VAMTX, PFMTX, +VAMTX) or vehicle. MTX administration reduced intestinal mucosal wet weight, protein and DNA concentrations, and sucrase and maltase activities in -VA and PF rats (P < 0.02). In Study 1, -VAMTX rats developed a severe jejunal enteropathy and had a higher incidence of diarrhea (P < 0.005), greater weight loss (P < 0.005), more disruption of villus architecture (P < 0.0001) and lower disaccharidase activity (P < 0.007) than PFMTX rats. Similar results were observed in Study 2. Liver retinol concentration (but no other variable) was greater in rats receiving 75 microg vitamin A/d (P < 0.001) than in those receiving 37.5 microg/d. The interaction of vitamin A deficiency and small intestinal injury may explain the efficacy of vitamin A supplementation in preventing childhood diarrheal disease mortality in developing countries, and highlights the need for ensuring adequate vitamin A status in people worldwide with diseases and/or treatments which may injure the gastrointestinal tract.

Administration, Oral↗

Functional biochemical and nutrient indices in frail elderly people are partly affected by dietary supplements but not by exercise.

A decline in dietary intake due to inactivity and, consequently, development of a suboptimal nutritional status is a major problem in frail elderly people. However, benefits of micronutrient supplementation, all-round physical exercise or a combination of both on functional biochemical and hematologic indicators of nutritional and health status in frail elderly subjects have not been tested thoroughly. A 17-wk randomized controlled trial was performed in 145 free-living frail elderly people (43 men, 102 women, mean age, 78 +/- 5.7 y). Based on a 2 x 2 factorial design, subjects were assigned to one of the following: 1) nutrient-dense foods, 2) exercise, 3) both (1) and (2) or 4) a control group. Foods were enriched with micronutrients, frequently characterized as deficient [25-100% of the recommended daily allowance (RDA)] in elderly people. Exercises focused on skill training, including strength, endurance, coordination and flexibility. Dietary intake, blood vitamin levels and nutritional and health indicators, including (pre)albumin, ferritin, transferrin, C-reactive protein, hemoglobin and lymphocytes were measured. At baseline, 28% of the total population had an energy intake below 6.3 MJ, up to a maximum of 93% having vitamin intakes below two thirds of the Dutch RDA. Individual deficiencies in blood at baseline ranged from 3% for erythrocyte glutathione reductase-alpha to 39% for 25-hydroxy vitamin D and 42% for vitamin B-12. These were corrected after 17 wk in the two groups receiving the nutrient-dense foods, whereas no significant changes were observed in the control or exercise group. Biochemical and hematologic indicators at baseline were within the reference ranges (mean albumin, 46 g/L; prealbumin, 0.25 g/L; hemoglobin, 8.6 mmol/L) and were not affected by any of the interventions. The long-term protective effects of nutrient supplementation and exercise, by maintaining optimal nutrient levels and thereby reducing the initial chance of developing critical biochemical values, require further investigation. Other indicative functional variables for suboptimal nutritional status, in addition to those currently selected, should also be explored.

Aged↗

Mass spectrometry methods for metabolic and health assessment.

Beginning in the mid 1960s, mass spectrometry was introduced in a few academic laboratories for the analysis of organic acids by gas chromatography-mass spectrometry. Since then, multiple-stage mass spectrometers have become available and many new applications have been developed. Major advantages of these new techniques include their ability to rapidly determine many different compounds in complex biological matrices with high sensitivity and in sample volumes of usually < 100 microL. A high sample throughput is further realized because extensive sample preparations are often not necessary. However, because the technical know-how is not yet widely available and significant experience is required for correct interpretation of results, these methods are being implemented slowly in routine clinical laboratories as opposed to research laboratories. Several of these new applications are considered with regard to clinical medicine.

Avitaminosis↗

DNA methylation and diet in cancer.

The studies reviewed here investigate the association between folate status and DNA methylation in cancer tissues. We evaluated tissue vitamin levels and global DNA methylation, a biomarker of neoplasia, in normal lung and lung cancer tissues. Lung squamous cell carcinoma tissues exhibited global DNA hypomethylation, with decreased folate and vitamin B-12 concentrations, and increased vitamin C concentrations, relative to matched uninvolved control tissues. Breast cancer tissues also had globally hypomethylated DNA and decreased vitamin B-12 and vitamin C levels, but folate concentrations were elevated in breast cancer tissues. Global DNA methylation status in buccal mucosal cells may reflect global methylation status in lung tissues, because there was a significant association between global DNA methylation in buccal mucosal cells and malignant tissues of the lung, but not between methylation in peripheral leukocytes and lung tissues. We found that global DNA hypomethylation, as assessed by a radiolabeled 5-methylcytosine technique, was associated with susceptibility for development of lung cancer, which is involved in the progression of the disease. DNA methylation was also associated with the development of squamous cell carcinomas in whites but not in blacks. Overall, these studies suggest that global DNA methylation patterns may vary depending on the type of cancer, that tissue vitamin levels are associated with global DNA methylation status and that ethnicity should be considered in studies of DNA methylation.

Age Factors↗