Effects of trace element and/or vitamin supplementation on vitamin and mineral status, free radical metabolism and immunological markers in elderly long term-hospitalized subjects. Geriatric Network MIN. VIT. AOX

A randomized double-blind trial was performed in order to assess the efficacity of differing combinations of antioxidant nutrients on biochemical parameters of vitamin and trace element status, immunological parameters and free radical metabolism in elderly long term hospitalized subjects. A total of 756 institutionalized elderly subjects were recruited in 26 nursing homes in different areas of France. Four groups were constituted, receiving daily, for 1 year, either vitamins (beta-carotene, 6 mg; vitamin C, 120 mg; and vitamin E, 15 mg), trace elements (zinc, 20 mg and selenium, 100 micrograms), trace elements associated with vitamins, or a placebo. Biochemical indicators of trace elements and vitamin status and free radical parameters were measured before and after 6 months and 1 year of supplementation. Some immunological markers were investigated initially and after 6 months of supplementation on a subsample of 134 subjects. Mean plasma levels of alpha-tocopherol, gamma-tocopherol, vitamin C, alpha-carotene, beta-carotene and copper increased significantly after 6 months of supplementation in groups receiving vitamins alone or associated with trace elements. Serum selenium concentrations were significantly increased at 6 months of supplementation, and serum zinc only after one year in the trace element groups. Serum lycopene levels were significantly decreased by trace element supplementation. A significant increase in Se-glutathione peroxidase (GPx) levels was observed in groups receiving trace elements alone or associated with vitamins. No effect was noted on superoxide dismutase (SOD) activity or TBARs production. No effect of supplementation was found for in vitro lymphocyte proliferative responses or most lymphocyte subsets, except for a significantly lower percentage of CD2 subsets observed in groups receiving mineral supplementation either alone or associated with vitamins. A significant difference in CD19 subsets was found in groups receiving trace elements. Mean IL-1 production was significantly higher after 6 months of supplementation in the vitamin groups.     

Trace element and vitamin concentrations and losses in critically ill patients treated with continuous venovenous hemofiltration

OBJECTIVES: To measure the blood concentrations of a number of trace elements and vitamins in critically ill patients and examine their elimination by continuous venovenous hemofiltration (CVVH). SETTING: Intensive care unit of a tertiary institution. DESIGN: Prospective, controlled, clinical study. PATIENTS: Eight critically ill patients requiring renal replacement therapy, nine patients requiring intensive care treatment but not requiring renal replacement therapy, and nine healthy controls. INTERVENTIONS: Measurement of trace element and vitamin concentrations in blood and ultrafiltrate. MEASUREMENTS AND MAIN RESULTS: Compared with normal volunteers, critically ill patients requiring CVVH had significantly lower median blood concentrations of vitamin C, vitamin E, selenium, and zinc. During the first 24 hrs of CVVH, there were no changes in the trace element and vitamin concentrations in blood, nor were there differences between pre- and postfilter samples. Micronutrient losses in the ultrafiltrate were small or undetectable except for Vitamin C, chromium, and copper. Compared with normal volunteers, critically ill patients not requiring CVVH also had significantly lower median blood concentrations of vitamin C, vitamin E, selenium, and zinc. There were no differences between the two critically ill groups. CONCLUSIONS: The clinical significance of the reductions in blood concentrations of selenium, zinc, vitamin C, and vitamin E in critically ill patients and the ultrafiltrate losses of Vitamin C, copper, and chromium remains unclear.     

A primary prevention trial using nutritional doses of antioxidant vitamins and minerals in cardiovascular diseases and cancers in a general population: the SU.VI.MAX study--design, methods, and participant characteristics. SUpplementation en VItamines et Minéraux AntioXydants

The SUpplementation en VItamines et Minéraux AntioXydants (SU.VI.MAX) Study is a randomized, double-blind, placebo-controlled, primary-prevention trial designed to test the efficacy of daily supplementation with antioxidant vitamins (vitamin C, 120 mg; vitamin E, 30 mg; and beta-carotene, 6 mg) and minerals (selenium, 100 microg; and zinc, 20 mg) at nutrition-level doses (one to three times the daily recommended dietary allowances) in reducing several major health problems in industrialized countries, especially the main causes of premature death, cancers and cardiovascular diseases. The present report describes the design, implementation, and baseline characteristics of participants in this 8-year cohort study, which started in 1994 in France; 12,735 eligible subjects (women aged 35-60, and men aged 45-60) were included in 1994 and will be followed for 8 years. Participants undergo a yearly visit consisting, every other year, of either biological sampling or clinical examination. They also regularly provide information on health events and dietary intake by filling out computerized questionnaires using the Minitel Telematic Network. Data on baseline characteristics of the participants suggest that the present sample is close to the national population in terms of geographic density, socioeconomic status, and the distribution of various major risk factors for the diseases under study. The choice of the study population should allow the results of this trial to apply to adult populations of both sexes in France and other industrialized countries.     

Developmental follow-up of 6-7 year old children of mothers employed during their infancies

The "SUpplementation en VItamines et MinérauxAntioXydants" (SU.VI.MAX) study is a randomized double-blind, placebo-controlled, primary prevention trial designed to test the efficacy of daily supplementation with antioxidant vitamins (vitamin C, 120 mg; vitamin E, 30 mg; and beta-carotene, 6 mg) and minerals (selenium, 100 micrograms; and zinc, 20 mg), at nutritional doses (one to three times the daily recommended dietary allowances), in reducing the frequency of major health problems in industrialized countries, and especially the main causes of premature death (cancers and cardiovascular diseases). The study involves 12,735 eligible subjects (women aged 35 to 60 years; men aged 45 to 60 years) included in 1994 in France. They will be followed up for 8 years. The objectives and the specific design of this intervention study are linked to its public health aim. The targeted population is the general population (not simply high-risk subjects) and the antioxidant agents tested are being administered at a level which is not pharmacologic and which may be attained by dietary intake of natural sources of these micronutrients and/or enriched foods. The amounts we are testing in the SU.VI.MAX study are those which, in observational studies have been associated with the lowest risk of diseases. This report presents the rationale and discusses the justification of the design, doses and combination of antioxidant micronutrients chosen in the SU.VI.MAX study.     

Age-associated problems in nutrition

From the chapters described so far, it is apparent that human beings may suffer many kinds of physiological declines during aging process. However, nutritional problems due to the physiological declines could be resolved by establishment of good eating patterns, intake of nutritionally balanced diet, appropriate nutrient supplementation of vitamins as well as minerals, and good nutrition program coupled with a regular exercise as mentioned in each chapters. Here is a Short Summary from the nutritional point of view for a longer, healthier, and more vital life. The balanced diet; especially the diet enhanced by vitamins E and B6 and trace mineral zinc is helpful for the elderly to prevent the declines in the immune system. The foods rich in vitamin D and calcium; they may help to prevent the elderly from osteoporosis. The foods with low fat, dietary cholesterol and sodium; these foods may be recommended for not only the elderly but also younger people to reduce the risk of cardiovascular disease. The good quality of diet; it is important for the elderly to avoid the monotonous diet because of their appetite declines.     

Vitamins E plus C and interacting conutrients required for optimal health. A critical and constructive review of epidemiology and supplementation data regarding cardiovascular disease and cancer

Antioxidants are crucial components of fruit/vegetable rich diets preventing cardiovascular disease (CVD) and cancer: plasma vitamins C, E, carotenoids from diet correlate prevalence of CVD and cancer inversely, low levels predict an increased risk of individuals which is potentiated by combined inadequacy (e.g., vitamins C + E, C + carotene, A + carotene); self-prescribed rectification of vitamins C and E at adequacy of other micronutrients reduce forthcoming CVD, of vitamins A, C, E, carotene and conutrients also cancer; randomized exclusive supplementation of beta-carotene +/- vitamin A or E lack benefits except prostate cancer reduction by vitamin E, and overall cancer reduction by selenium; randomized intervention with synchronous rectification of vitamins A + C + E + B + minerals reduces CVD and counteracts precancerous lesions; high vitamin E supplements reveal potentials in secondary CVD prevention. Plasma values desirable for primary prevention: > or = 30 mumol/l lipid-standardized vitamin E (alpha-tocopherol/cholesterol > or = 5.0 mumol/mmol); > or = 50 mumol/l vitamin C aiming at vitamin C/vitamin E ratio > 1.3-1.5; > or = 0.4 mumol/l beta- (> or = 0.5 mumol/l alpha+ beta-) carotene. CONCLUSIONS: In CVD vitamin E acts as first risk discriminator, vitamin C as second one; optimal health requires synchronously optimized vitamins C + E, A, carotenoids and vegetable conutrients.     

Procoagulant and proinflammatory activity in acute coronary syndromes

Free-living elderly people aged > or = 65 y were recruited to assess riboflavin and vitamin B-6 intakes and status and the effect of riboflavin supplementation on biochemical indicators of these 2 vitamins. The status of riboflavin (erythrocyte glutathione reductase activation coefficient; EGRAC) and vitamin B-6 (plasma pyridoxal-5'-phosphate; PLP) were determined in a total sample of 92 subjects, from whom dietary intake data were obtained by using the diet history method (n = 83). Although dietary intakes of both vitamins were considered to be adequate according to current reference values, abnormal EGRAC and plasma PLP values were identified in 49% and 38% of subjects, respectively, with 21% having suboptimal status for both nutrients. A subgroup of subjects from the initial sample (n = 45) was assigned in a double-blind manner to receive either 1.6 or 25 mg riboflavin or placebo daily for 12 wk. In those subjects with a baseline EGRAC or plasma PLP value falling outside the currently accepted threshold value for adequacy, low-dose riboflavin supplementation improved status of the limiting nutrient significantly (P<0.0001 and P = 0.020 for EGRAC and plasma PLP responses, respectively). We conclude that a high proportion of healthy elderly people may have suboptimal status for these nutrients despite apparently adequate dietary intakes. Furthermore, we showed that riboflavin supplementation at physiologic doses corrects biochemical abnormalities of not only EGRAC, but also plasma PLP, confirming the biochemical interdependency of these vitamins and suggesting that riboflavin is the limiting nutrient.     

Vitamin requirements for the treatment of hyperhomocysteinemia in humans

We have previously shown that a modest vitamin supplement containing folic acid, vitamin B-12 and vitamin B-6 is effective in reducing elevated plasma homocysteine concentrations. The effect of supplementation of the individual vitamins on moderate hyperhomocysteinemia has now been investigated in a placebo-controlled study. One hundred men with hyperhomocysteinemia were randomly assigned to five groups and treated with a daily dose of placebo, folic acid (0.65 mg), vitamin B-12 (0.4 mg), vitamin B-6 (10 mg) or a combination of the three vitamins for 6 wk. Folic acid supplementation reduced plasma homocysteine concentrations by 41.7% (P < 0.001), whereas the daily vitamin B-12 supplement lowered homocysteine concentrations by 14.8% (P < 0.01). The daily pyridoxine dose did not reduce significantly plasma homocysteine concentrations. The combination of the three vitamins reduced circulating homocysteine concentrations by 49.8%, which was not significantly different (P = 0.48) from the reduction achieved by folate supplementation alone. Our results indicate that folate deficiency may be an important cause of hyperhomocysteinemia in the general population.     

Consequences of hyperhomocyst(e)inemia on vascular function in atherosclerotic monkeys

Moderate elevation of plasma homocyst(e)ine is associated with increased risk for atherosclerotic vascular disease. In a previous study, we observed impaired vascular function in nonatherosclerotic monkeys with moderate hyperhomocyst(e)inemia. In this study, we tested the hypothesis that dietary intervention to lower plasma homocyst(e)ine corrects vascular dysfunction in atherosclerotic monkeys. Cynomolgus monkeys were fed an atherogenic diet that produces both hypercholesterolemia and moderate hyperhomocyst(e)inemia. After 17 months, the atherogenic diet was supplemented with B vitamins (5 mg folic acid, 400 micrograms vitamin B-12, and 20 mg vitamin B-6 daily) for 6 months. Total plasma homocyst(e)ine decreased from 12.8 +/- 2.8 to 3.5 +/- 0.3 mumol/L (n = 9; mean +/- SE; P < .01) after vitamins were added to the diet, but plasma cholesterol remained elevated (522 +/- 63 versus 514 +/- 41 mg/dL; P > .05). In response to intra-arterial infusion of collagen, blood flow to the leg decreased by 30 +/- 3% and 38 +/- 5%, respectively, before and after vitamin supplementation (P > .05). In vivo responses of resistance vessels to endothelium-dependent vasodilators (acetylcholine or ADP) were impaired at baseline and did not improve after vitamin supplementation. In carotid artery studied ex vivo, relaxation to low doses of acetylcholine improved after vitamin supplementation, but maximal relaxation remained impaired. Ex vivo thrombomodulin anticoagulant activity was threefold higher in monkeys fed the atherogenic diet (with or without B vitamins) than in normal monkeys (P < .05). We conclude that normalization of plasma homocyst(e)ine is insufficient to restore normal vascular function in atherosclerotic monkeys with persistent hypercholesterolemia and that atherosclerosis, with or without hyperhomocyst(e)inemia, is associated with elevated thrombomodulin activity.     

Serum beta-carotene and antioxidant micronutrients in children with cancer. The 'Cancer in Children and Antioxidant Micronutrients' French Study Group

Serum antioxidant vitamins A (retinol) and E (alpha-tocopherol), beta-carotene, zinc and selenium for 418 children with newly diagnosed malignancy were compared with those of 632 cancer-free controls. Incident cancer cases and controls were 1-16 years old and recruited in 1986-1989. Age- and sex-adjusted serum concentrations of retinol, beta-carotene and alpha-tocopherol were significantly inversely associated with cancer. In similar models, the odds ratio (OR) comparing the highest with the lowest quintile was 2.06 (95% confidence interval [CI] 1.40-3.02) for retinol, 3.87 (95% CI: 2.54-5.90) for beta-carotene, 2.15 (95% CI: 1.48-3.10) for alpha-tocopherol, 1.29 (95% CI: 0.75-2.23) for selenium, and 1.94 (95% CI: 1.17-2.23) for zinc. The cancer sites that were associated with serum beta-carotene were, in general, leukaemia, lymphoma, central nervous system, bone and renal tumours. Moreover, leukaemia was associated with low mean serum levels of retinol, selenium and zinc. Subjects with lymphoma, bone and renal tumours also had lower mean retinol and alpha-tocopherol levels than controls. Brain tumour patients had low vitamin E levels. Low serum values of antioxidant vitamins were associated with childhood neoplasm occurrence. Some site-specific effect was reported. Low peripheral nutrient levels are not considered as cancer promoters but rather as an impairment of the body's defence mechanism occurring during the cancer-related metabolic and nutritional disturbances and inflammation processes.     

A double-blind, placebo-controlled, dose-ranging safety evaluation of single-dose intravenous dolasetron in healthy male volunteers

The safety and tolerability of dolasetron mesylate, a potent and selective 5-HT3 receptor antagonist, were evaluated after single intravenous doses in healthy male volunteers. In this double-blind, placebo-controlled, randomized, phase I study, 80 subjects received either placebo or dolasetron in escalating doses (0.6 to 5.0 mg/k). Subjects were monitored for adverse events, vital sign and laboratory alterations, and changes in electrocardiographic (ECG) intervals and electroencephalographic (EEG) patterns. Overall, the percentage of subjects reporting adverse events was similar in those receiving dolasetron (44/64; 68.8%) or placebo (10/16; 62.5%); most adverse events were mild in severity. Subjects receiving dolasetron reported a higher incidence of central nervous system (headache and dizziness/lightheadedness), gastrointestinal (increased appetite and nausea), and visual adverse events and taste alterations. No clinically significant changes in laboratory variables were observed. Transient and asymptomatic ECG changes (small mean increases in PR interval and QRS complex duration versus baseline) were noted in several subjects at 1 to 2 hours after infusion at doses > or = 3.0 mg/kg. Transient, mild blood pressure decreases were observed in five subjects, including one on placebo. Dolastron mesylate was well tolerated in single intravenous doses up to 5.0 mg/kg in healthy male volunteers. Clinical studies of the drug are ongoing for antiemetic indications.     

Blood vitamins, mineral elements and inflammation markers as risk factors of vascular and non-vascular disease mortality in an elderly population

BACKGROUND: The need for protecting agents against degenerative processes of the body has been proposed to be especially high in elderly people. In order to evaluate the prognostic value of various biochemical factors in ageing the associations of blood concentrations of several vitamins, mineral elements and some other suggested risk factors with vascular and non-vascular mortality were studied in an elderly population. METHODS: A large health survey with complete clinical evaluation was carried out in the City of Turku in 1982-1983. A random sample of 344 community-living elderly individuals aged 65 years or older, stratified into four age groups, was studied. During the 13 years follow-up 225 subjects had died. Calcium, magnesium, copper, ceruloplasmin, zinc, selenium, iron, ferritin, transferrin, alpha-tocopherol, retinol, folate, vitamin B12, malondialdehyde, orosomucoid and insulin levels were analysed from the blood specimens. The relations between the compounds measured and relative mortality risks during the 13-year follow-up were analysed by Cox proportional hazards model adjusting for other known risk factors. RESULTS AND CONCLUSIONS: High concentrations of serum copper, orosomucoid and insulin were associated with increased risk of vascular mortality. The relative risks within the subjects of the highest tertile of serum concentrations were 2.2 for copper, 1.8 for orosomucoid, and 1.8 for insulin when adjusted for many confounding risk factors. Low serum vitamin B12 concentrations appeared to be significantly (P = 0.01) associated with increased vascular mortality. The associations were essentially not more significant when adjusted only for age. Contrary to earlier observations concentrations of serum magnesium, selenium, alpha-tocopherol, iron and its binding proteins or plasma and erythrocyte folate were not associated with increased mortality risk when adjusted for confounding risk factors. The authors suggest that in elderly subjects these elements and compounds are at the most weak, and probably non-independent risk factors for vascular mortality.     

Selenium (Se) deficiency in women with ovarian cancer undergoing chemotherapy and the influence of supplementation with this micro-element on biochemical parameters

A clinical study was undertaken to evaluate the influence of a preparation containing selenium and vitamins with antioxidant properties (Protecton Zellaktiv from Smith Kline Naturarznei-Germany) on: (a) concentration of Se in serum and hair, (b) activity of glutathione peroxidase (GSH-Px), and (c) concentration of malondialdehyde (MDA) in serum, before and during supplementation. Women undergoing chemotherapy for ovarian cancer received selenium during three months at a daily dose of 200 micrograms. The results were compared with controls not receiving selenium supplementation. Administration of selenium significantly increased the serum and hair concentrations of selenium in the study group. After three months of supplementation the activity of GSH-Px was significantly higher in the study group. After one month of supplementation a difference in the concentration of MDA between the study and control groups was found. On the basis of the present results the administration of selenium in patients with ovarian cancer undergoing multi-drug chemotherapy is recommended.     

Role of the microbiology laboratory in the diagnosis of lower respiratory tract infections

A randomized, double-blind trial was undertaken to measure the effects of zinc supplementation on catch-up growth in severe protein-energy malnutrition, with particular reference to linear growth. One hundred forty-one children between the ages of 6 mo and 3 y were enrolled after admission to a nutritional rehabilitation unit in Dhaka, Bangladesh, and randomly assigned to receive elemental zinc by mouth, 1.5 mg/kg for 15 d, 6.0 mg/kg for 15 d, or 6.0 mg/kg for 30 d, and thereafter they were followed for a total of 90 d. Anthropometric outcome measures included change in knee-heel length, midupper arm circumference, subscapular and triceps skinfold thicknesses, and change in height-for-age, weight-for-age, and weight-for-height z scores. Higher zinc doses were not associated with significant change in any anthropometric measurement, but mortality was significantly greater in children who received high-dose zinc (6.0 mg/kg) initially as opposed to those who received low-dose zinc supplementation (1.5 mg/kg) (Yates-corrected chi-square P value of 0.033 and a risk ratio of 4.53; 95% CI: 1.09 < risk ratio < 18.8). We conclude that there is no benefit to using high-dose zinc supplementation regimens and that they could contribute to increased mortality in severely malnourished children.     

Improvement of epileptic seizure control with treatment of obstructive sleep apnoea

Modified LDL, caused by many factors, is associated with increased atherogenisity. In many modified LDLs, it is recognized that LDL oxidation occurs in vivo, and oxidized LDL demonstrates enhanced cellular uptake by macrophage scavenger receptor, foam cell formation. In vitro, iron and zinc are necessary for oxidized LDL and lipid peroxisides, and considering these elements to participate in vivo, particularly hyperlipidemia. In fact, hyperlipidemia with high serum levels iron or zinc concentration is a risk factor of coronary heart disease. Further, the possibility of selenium insufficiency accelerated lipid peroxisides in vivo, because glutathione peroxidase (GSHPx), the antioxidant effect, includes selenium, and GSHPx hyperproduction are recognized in atherosclerotic lesion. It is known that oxidized LDL are more excessive in hyperlipidemia, so hyperlipidemia may suffer more from trace element status in vivo. Enzymes and hormones, influencing lipid metabolism, are necessary for many trace elements their activation. Trace elements may therefore, be important in several stage of lipid metabolism.     

Fine-needle aspiration biopsy findings in a case of follicular dendritic cell tumor

OBJECTIVES: To measure blood selenium concentration and glutathione peroxidase (GSH-Px) activity and serum concentrations of vitamin A and alpha-tocopherol, and to determine the correlation between blood selenium concentration and GSH-Px activity of llamas fed alfalfa hay. DESIGN: Mean (+/- SD) serum vitamin A and alpha-tocopherol concentrations, blood selenium concentrations, and GSH-Px activity were calculated from 9 sequential blood samples collected from llamas fed a diet of alfalfa hay. ANIMALS: 15 clinically normal llamas (8 males, 7 females) between 10 and 14 months of age. PROCEDURE: Llamas were fed alfalfa hay for 40 days prior to sample collection and then for the duration of the trial. Vitamin E, selenium, and concentrations of vitamin A precursors were measured in the hay. Blood samples were collected on days 0, 6, 7, 9, 13, 20, 42, 64, and 98. Blood selenium concentrations were measured, using an inductively coupled spectrometric method. Blood GSH-Px activity was measured with a spectrophotometer, using a modification of a previously described assay. Isocratic high-performance liquid chromatography with florescent detection was used to determine serum alpha-tocopherol and vitamin A concentrations. RESULTS: The alfalfa hay contained 0.2 mg/kg of selenium, 5 mg/kg of vitamin E, and 0.9 mg/kg of vitamin A precursors. The mean (+/- SD) blood selenium concentration and GSH-Px activity were 0.179 +/- 0.032 micrograms/ml and 25.76 +/- 6.53 mU NADPH oxidized/min/mg of Hb, respectively, with a correlation coefficient of 0.97. The mean (+/- SD) concentrations for serum alpha-tocopherol and vitamin A were 128.1 +/- 41.7 and 74.8 +/- 5.5 micrograms/dl, respectively. CONCLUSIONS: Blood selenium concentrations in llamas are highly correlated to GSH-Px activity. Blood selenium concentrations in llamas appear to be similar to other domestic ruminants and diets containing 0.2 mg/kg of selenium appear to provide an adequate dietary source. The concentrations of vitamin A precursors and vitamin E in the hay were below currently recommended dietary levels for llamas, and alfalfa hay appears to provide an unreliable source of vitamins A and E in this species. Further studies are required to determine optimal dietary concentrations and to substantiate a reference range for these vitamins in llamas.     

Concentrations of selected vitamins and selenium in bison cuts

We analyzed individual cuts from clod (Triceps brachii), ribeye (Longissimus thoracis), top round (semimembranosus), and top sirloin (Gluteus medius) from 12 fed bison bulls for content of selected vitamins and selenium. The bulls came from producers in the United States and Canada and had consumed concentrate diets plus hay free choice for at least 180 d. The mean nutrient concentrations of all of the bison cuts combined were as follows (per 100 grams of wet weight): .045 mg thiamin, .253 mg vitamin B6, 2.131 microg vitamin B12, no detectable vitamin C, .848 microg vitamin A, .047 mg alpha-tocopherol, .013 mg tau-tocopherol, and 25.464 microg selenium. The nutrient content values did not differ (P > .05) among the cuts of meat. Cuts from individual bulls were different (P < .05) with regard to alpha- and tau-tocopherols, selenium, and vitamin A but not with regard to thiamin, vitamin B6, and vitamin B12. Nutrient concentrations, with the exception of one nutrient, of five bison from the same producer were similar. Great variation was observed between the alpha- and tau-tocopherols, selenium, and vitamin A contents among bison bulls but not among cuts of meat.     

Benefit of oral zinc supplementation as an adjunct to zidovudine (AZT) therapy against opportunistic infections in AIDS

Zinc is perhaps the most important trace element for immune function. Congenital or acquired zinc deficiencies are associated with immune abnormalities and increased susceptibility to infectious diseases. AIDS subjects suffer from reduced zinc bioavailability, more severe in stage IV than in stage III. Such zinc deficiency causes, among other effects, a profound reduction in the biological activity of one of the thymic hormones, thymulin (zinc-facteur-timique-serique, ZnFTS). With these premises, zinc sulphate was administered orally at a daily dose of 200 mg for 30 days to AZT-treated stage III subjects with generalized lymphadenopathy (17 subjects) and stage IV subgroup C1 (12 subjects) AIDS patients. 18 stage III subjects with generalized lymphoadenopathy and 10 stage IV subgroup C1 subjects treated only with AZT served as controls. Zinc sulphate supplementation of stage III and in stage IV C1 patients was followed by an increase or a stabilization in the body weight and an increase of the number of CD4+ cells and the plasma level of active zinc-bound thymulin. The frequency of opportunistic infectious episodes in the 24 months following entry into the study was reduced after zinc supplementation in stage IV C1 subjects (11 infections vs 25 in controls) and delayed in stage III zinc-treated subjects (1 infection/24 months vs 13 infections/24 months in controls). The effect of zinc on opportunistic infections is restricted to infections due to Pneumocystis carinii and Candida, whereas no variations have been observed in the frequencies of cytomegalovirus and toxoplasma infections. These data may support the benefit of zinc as an adjunct to AZT therapy in AIDS pathology.     

Development and evaluation of peptide-based prolyl oligopeptidase inhibitors--introduction of N-benzyloxycarbonyl-prolyl-3-fluoropyrrolidine as a lead in inhibitor design

Different supplementation schemes to build iron stores in female Indonesian adolescents were investigated. Subjects were 273 high-school girls allocated randomly to four treatment groups. During a 3-mo period one group received 60 mg Fe, 750 micrograms retinol, 250 micrograms folic acid, and 60 mg vitamin C per day; a second group received 60 mg Fe, 6000 micrograms retinol, 500 mg folic acid, and 60 mg vitamin C once a week; a third group received 120 mg Fe and the same amount of the other three micronutrients as the second group once a week; and a fourth group received only placebos. All subjects were dewormed and supplement allocation was double blind. Blood samples were collected at baseline, after 2 and 3 mo of supplementation, and 6 mo after the last supplement. After 2 mo of supplementation, groups supplemented weekly and daily showed similar significant improvements (P < 0.001) in hemoglobin and retinol concentrations, and supplementation for 3 instead of 2 mo did not significantly increase these two indicators. After 3 mo, the increase in ferritin was approximately equal to 27 micrograms/L in the daily and 14-15 micrograms/L in the weekly groups (P < 0.001), the latter having a final concentration of 42-45 micrograms/L. At 6 mo postsupplementation there were no significant differences among daily and weekly groups, but the ferritin concentration was still approximately equal to 10-12-micrograms/L higher (P < 0.001) than in the placebo group. The group supplemented weekly with 60 mg Fe complained less about side effects than the other supplemented groups (P < 0.05). Weekly supplementation with 60 mg Fe and 6000 micrograms retinol for 3 mo was optimal for improving the iron status of the adolescents for approximately equal to 9 mo.     

Attenuation of gossypol cytotoxicity by cyclic AMP in a rat liver cell line

We showed previously that supplementation for 30 d with 800 IU (727 mg) vitamin E/d did not adversely affect healthy elderly persons. We have now assessed the effects of 4 mo of supplementation with 60, 200, or 800 IU (55, 182, or 727 mg) all-rac-alpha-tocopherol/d on general health, nutrient status, liver enzyme function, thyroid hormone concentrations, creatinine concentrations, serum autoantibodies, killing of Candida albicans by neutrophils, and bleeding time in 88 healthy subjects aged >65 y participating in a double-blind, placebo-controlled trial. No side effects were reported by the subjects. Vitamin E supplementation had no effect on body weight, plasma total proteins, albumin, glucose, plasma lipids or the lipoprotein profile, total bilirubin, alkaline phosphatase, serum aspartate aminotransferase, serum alanine aminotransferase, lactate dehydrogenase, serum urea nitrogen, total red blood cells, white blood cells or white blood cell differential counts, platelet number, bleeding time, hemoglobin, hematocrit, thyroid hormones, or urinary or serum creatinine concentrations. Values from all supplemented groups were within normal ranges for older adults and were not significantly different from values in the placebo group. Vitamin E supplementation had no significant effects on plasma concentrations of other antioxidant vitamins and minerals, glutathione peroxidase, superoxide dismutase, or total homocysteine. There was no significant effect of vitamin E on serum nonspecific immunoglobulin concentrations or anti-DNA and anti-thyroglobulin antibodies. The cytotoxic ability of neutrophils against Candida albicans was not compromised. Thus, 4 mo of supplementation with 60-800 IU vitamin E/d had no adverse effects. These results are relevant for determining risk-to-benefit ratios for vitamin E supplementation.