Effects Of Long-term Vitamin Research Articles

The effect of long-term vitamin E and C therapy on coronary microvascular endothelial function in patients with coronary disease: A prospective randomized trial Marco V. Wainstein, Jason Ganz, Dominik Behrendt, James C. Fang, Jason Morrow, Peter Ganz, Andrew Selwyn, Scott Kinlay. Brigham and Women's Hospital, Boston, MA, Linus Pauling Institute, Corvallis, OR

The effect of long-term vitamin E and C therapy on coronary microvascular endothelial function in patients with coronary disease: A prospective randomized trial Marco V. Wainstein, Jason Ganz, Dominik Behrendt, James C. Fang, Jason Morrow, Peter Ganz, Andrew Selwyn, Scott Kinlay. Brigham and Women's Hospital, Boston, MA, Linus Pauling Institute, Corvallis, OR

Supplementation with vitamin E but not with vitamin C lowers lipid peroxidation in vivo in mildly hypercholesterolemic men

Although the use of vitamin E supplements has been associated with a reduction in coronary events, assumed to be due to lowered lipid peroxidation, there are no previous long-term clinical trials into the effects of vitamin C or E supplementation on lipid peroxidation in vivo. Here, we have studied the long-term effects of vitamins C and E on plasma F2-isoprostanes, a widely used marker of lipid peroxidation in vivo. As a study cohort, a subset of the “Antioxidant Supplementation in Atherosclerosis Prevention” (ASAP) study was used. ASAP is a double-masked placebo-controlled randomized clinical trial to study the long-term effect of vitamin C (500 mg of slow release ascorbate daily), vitamin E (200 mg of d-α-tocopheryl acetate daily), both vitamins (CellaVie®), or placebo on lipid peroxidation, atherosclerotic progression, blood pressure and myocardial infarction (n = 520 at baseline). Lipid peroxidation measurements were carried out in 100 consecutive men at entry and repeated at 12 months. The plasma F2-isoprostane concentration was lowered by 17.3% (95% CI 3.9–30.8%) in the vitamin E group (p = 0.006 for the change, as compared with the placebo group). On the contrary, vitamin C had no significant effect on plasma F2-isoprostanes as compared with the placebo group. There was also no interaction in the effect between these vitamins. In conclusion, long-term oral supplementation of clinically healthy, but hypercholesterolemic men, who have normal vitamin C and E levels with a reasonable dose of vitamin E lowers lipid peroxidation in vivo, but a relatively high dose of vitamin C does not. This observation may provide a mechanism for the observed ability of vitamin E supplements to prevent atherosclerosis.

Oral vitamin C and endothelial function in smokers: short-term improvement, but no sustained beneficial effect

OBJECTIVESTo test the hypothesis that antioxidant therapy would improve endothelial function in smokers.BACKGROUNDSeveral studies have documented a beneficial effect of short-term oral or parenteral vitamin C on endothelial physiology in subjects with early arterial dysfunction. Possible long-term effects of vitamin C on endothelial function, however, are not known.METHODSWe studied the effects of short- and long-term oral vitamin C therapy on endothelial function in 20 healthy young adult smokers (age 36 ± 6 years, 8 male subjects, 21 ± 10 pack-years). Each subject was studied at baseline, 2 h after a single dose of 2 g vitamin C and 8 weeks after taking 1 g vitamin C daily, and after placebo, in a randomized double-blind crossover study. Blood samples were analyzed for plasma ascorbate levels and endothelial function was measured as flow-mediated dilation of the brachial artery, using high resolution ultrasound. Nitroglycerin-mediated dilation (endothelium-independent) was also measured at each visit.RESULTSAt baseline, plasma ascorbate level was low in the smokers (42 ± 21 μmol/liter; normal range, 50 to 150 μmol/liter), increased with vitamin C therapy after 2 h to 120 ± 54 μmol/liter (p < 0.001) and remained elevated after eight weeks of supplementation at 92 ± 32 μmol/liter (p < 0.001, compared with placebo). Flow-mediated dilation, however, increased at 2 h (from 2.8 ± 2.0% to 6.3 ± 2.8%, p < 0.001), but there was no sustained beneficial effect after eight weeks (3.9 ± 3.2%, p = 0.26). Nitroglycerin-mediated dilation was unchanged throughout.CONCLUSIONOral vitamin C therapy improves endothelial dysfunction in the short term in healthy young smokers, but it has no beneficial long-term effect, despite sustained elevation of plasma ascorbate levels.

Effects of Long-Term Vitamin E and Butylated Hydroxytoluene Supplemented Diets on Murine Intestinal and Hepatic Antioxidant Enzyme Activities

Effects of Long-Term Vitamin E and Butylated Hydroxytoluene Supplemented Diets on Murine Intestinal and Hepatic Antioxidant Enzyme Activities

Effects of long-term vitamin E supplementation in alcoholic cirrhotics.

Alcohol ingestion promotes lipoperoxidation and alters cellular antioxidant mechanisms. Alpha-tocopherol levels decrease in alcoholics as severity of liver damage increases. The aim of this protocol was to study the effects of a long-term oral 500 mg vitamin E daily supplementation in decompensated ambulatory alcoholic cirrhotics. 67 subjects were included in this double blind trial; 33 patients received vitamin E and 34 patients received placebo tablets of identical appearance during 1 year. Each month, the patients were seen by a nurse practitioner who was in charge of detecting alcohol ingestion and checking adherence to treatment. Every 3 months, the patients underwent a medical examination, and blood samples were taken for clinical laboratory analysis and serum vitamin E measurement. Alpha-tocopherol levels were significantly lower in patients with more severe liver disease. This difference was not significant when vitamin E levels were corrected by cholesterol. Oral supplementation significantly increased serum vitamin E levels in the experimental group. Alcohol ingestion and hospitalization rates were similar in both groups. Life table analysis did not show significant differences in mortality between the two groups. Vitamin E supplementation with adequate doses of an alpha-tocopheryl acetate formulation during 1 year did not influence hepatic laboratory parameters, mortality or hospitalization rates of decompensated alcoholic cirrhotics, although serum levels of the vitamin significantly increased.

Learning behaviour in chronic vitamin E-deficient and-supplemented rats: radial arm maze learning and passive avoidance response

The effects of long-term vitamin E deficiency and supplementation on learning behaviour were investigated. Rats were fed vitamin E-deficient [VE(-)], -supplemented [VE(+)], or control standard food beginning after the age of 4 weeks. They were trained in an eight-arm radial maze learning task at the age of 17 months, and in a step-through passive avoidance response (PAR) task at the age of 25 months. In the radial maze task, both VE(-) and VE(+) animals required as many trials to reach the learning criterion as control animals. Scopolamine injection (0.25-0.5 mg/kg) after acquisition of the task decreased the number of correct choices dose-dependently; however, the degree of the drug effect on VE(-) and VE(+) rats did not differ from that on control rats. On the other hand, VE(-) animals showed significantly lower rate of avoidance response and VE(+) animals tended to show higher rate of avoidance response in the PAR task than did control animals. These results suggest that long-term vitamin E deficiency or supplementation does not influence general ability to acquire and maintain memory tasks in rats, but that it may affect learning behaviour, depending on the kind of task in which animals were trained.

Variations in the level of transferrin and SGP-2 mRNAs in Sertoli cells of vitamin A-deficient rats

Stage-specific levels and long-term effects of vitamin A deficiency on transferrin and sulfated glycoprotein-2 (SGP-2) mRNAs were analyzed in normal rats and in rats fed a vitamin A-deficient diet for 49 days (49 day VAD) and 77 days (77 day VAD). Histological sections of testes from these animals were hybridized in situ with single stranded 3H-labeled RNA probes complementary to the transferrin and SGP-2 (clusterin) mRNAs prepared from specific cDNAs subcloned in the SP65 vector. In all cases the probes were visualized and quantified by radioautography. Vitamin A deficiency (49 day VAD rats) differentially affected the levels of these mRNAs by increasing significantly the level of SGP-2 transcripts and decreasing the level of transferrin mRNA. However, in both cases the stage-specific pattern characteristic of the normal testes remained cyclic indicating that the specific interactions between germ cells and Sertoli cells may play an important role in modulating the cyclic activities of Sertoli cells. The data also indicated that dividing spermatocytes, secondary spermatocytes and steps 13-14 spermatids were associated with Sertoli cells expressing high levels of transferrin mRNA, while steps 7, 8 and particularly 19 spermatids were associated with Sertoli cells expressing high levels of SGP-2 mRNA. In contrast to the shorter term, a longer term of vitamin A deficiency (77 day VAD rats) produced a significant decrease in the levels of both transferrin and SGP-2 mRNAs.

Alterations in rat epidermis provoked by chronic vitamin D deficiency.

Long-term effects of vitamin D deficiency on epidermis were studied using histometric techniques, [3H]thymidine incorporation into DNA (labeling index), estimation of epidermal acid phosphatase activity, and one-dimensional gel electrophoresis of keratin proteins. The decrease in epidermal thickness due to a reduced number of granular cell layers and a lower level of epidermal acid phosphatase activity were observed in vitamin D-deficient rats. The number of nuclei in the basal layer was increased. No changes in labeled index due to chronic vitamin D deficiency or to 'single injection of 1,25-dihydroxycholecalciferol to vitamin D-deficient rats were observed. A comparative study of the keratin composition revealed differences in the keratin polypeptide pattern: vitamin D-deficient epidermis specifically lacked two low-molecular-weight components and presented several quantitative differences among other keratin polypeptides. The changes in epidermal morphology and metabolism that took place with vitamin D deficiency were independent of plasma calcium levels because similar modifications were present in vitamin D-deficient but normocalcemic rats (fed a diet rich in calcium and supplemented with lactose). These findings suggest that vitamin D may be one of the important factors for maintaining normal epidermal structure and metabolism through an effect on cell differentiation and formation of granular cell layers. They offer the possibility of using epidermal modification as an additional marker of vitamin D deficiency.

Effects of long-term vitamin E deficiency and restoration on rat hepatic peroxisomes

Effects of vitamin E deficiency and its restoration on biochemical characteristics of hepatic peroxisomes were studied. Rats were maintained on the vitamin E-deficient diet for 25 weeks and then on a diet supplemented with vitamin E for 5 weeks. Blood hemolysis by hydrogen peroxide and lipid peroxidation in the liver increased markedly in vitamin E-deficient rats. The former returned to the control level after the resupplying of vitamin E, but the latter did not. Of liver peroxisomal enzymes, the activities of catalase, d-amino-acid oxidase and urate oxidase decreased in vitamin E-deficient rats. On the other hand, activities of fatty acyl-CoA oxidase and carnitine acetyltransferase increased significantly in vitamin E-deficient rats. All activities of these peroxisomal enzymes were restored to the control levels in vitamin E-supplmented rats. The activities of the mitochondrial, lysosomal and microsomal enzymes tested showed no apparent change except that the change of mitochondrial palmitoyltransferase was shown to be similar to that of peroxisomal fatty acid oxidation. These results were also supported by cell fractionation techniques. Following the methods of aqueous polymer two-phase systems, the characteristics of peroxisomal surface membranes altered in respect of their hydrophobicity, but not in respect of the surface charge of peroxisomal membranes. These results indicate that peroxisomal functions, especially those of the fatty acid oxidation system, change their activities more sensitively than other intracellular organelles in response to the condition of vitamin E deficiency.

Effects of long-term vitamin D deficiency and response to vitamin D repletion in the mature and aging male and female rat

This study investigated the sex- and age-related alterations in calcium homeostasis in 39- to 82-week-old rats raised from weaning on a vitamin D deficient (−D) diet. It was found that vitamin D deprivation decreased the life span of male, but not female, rats. Female −D animals exhibited a study increase in serum calcium with age of 39 to 82 weeks, although circulating calcium of −D animals never reached normocalcemic levels. There was no attenuation of the secondary hyperparathyroidism. Serum calcium of −D males was significantly lower than that of age-matched females at all ages when sufficient males were alive to make the comparison. Serum parathyroid hormone levels were decreased in −D females when serum clacium was elevated to hypercalcemic levels by calcium injection. Similarly, administration of vitamin D 3 or 1,25-dihydroxyvitamin D 3 elevated serum calcium and depressed parathyroid hormone in 14- and 22-month-old −D females. These animals also exhibited increased intestinal calcium binding protein content. Administration of vitamin D 3 or dihydroxyvitamin D 3 repaired renal adenylate cyclase refractoriness to parathyroid hormone. The sex- and diet-related alterations in serum phosphorus that were found at earlier ages disappeared by 67 weeks of age. Serum calcitonin was elevated in mature and aging +D males and females and −D females relative to younger animals. In −D males, calcitonin levels were less markedly elevated. The results of this study indicate that there are several important sex differences related to the regulation of calcium homeostasis in mature and aging rats. In addition, it was found that mature (14 month) and old (22 month) chronically −D female rats were able to respond to repletion with dihydroxyvitamin D 3 or vitamin D within 10 days.

Effects of vitamin D metabolites and analogues on renal function.

The long-term effects of vitamin D analogues and metabolites on renal function were assessed in 24 patients with and without chronic renal failure. Treatment for periods of 5-45 months did not adversely affect renal function in 10 of 11 patients with stable renal function, although transient hypercalcaemia did cause transient rises in plasma creatinine. Of 13 patients with progressive renal failure before treatment, vitamin D-like compounds or the vehicle used for their administration may have accelerated renal failure in 3 patients independently of changes in plasma calcium or phosphate. Particular difficulties in assessing the effects of vitamin D-like compounds in progressive renal disease are discussed.