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UV photoprotection by combination topical antioxidants vitamin C and vitamin E.

BACKGROUND: Virtually all plants and animals protect themselves from the sun using vitamins C and E. OBJECTIVE: The purpose of this study was to see if a combination of topical vitamins C and E is better for UV protection to skin than an equivalent concentration of topical vitamin C or E alone. METHODS: We developed a stable aqueous solution of 15% L-ascorbic acid (vitamin C) and 1% alpha-tocopherol (vitamin E). We applied antioxidant or vehicle solutions to pig skin daily for 4 days. We irradiated (1-5x minimal erythema dose) control- and antioxidant-treated skin using a solar simulator with a 295-nm band-pass filter. On day 5, we measured antioxidant protection factor, erythema, sunburn cells, and thymine dimers. RESULTS: The combination of 15% L-ascorbic acid and 1% alpha-tocopherol provided significant protection against erythema and sunburn cell formation; either L-ascorbic acid or 1% alpha-tocopherol alone also was protective but the combination was superior. Application during 4 days provided progressive protection that yielded an antioxidant protection factor of 4-fold. In addition, the combination of vitamins C and E provided protection against thymine dimer formation. CONCLUSION: Appreciable photoprotection can be obtained from the combination of topical vitamins C and E. We suggest that these natural products may protect against skin cancer and photoaging.

Animals↗

Plasma total homocysteine response to oral doses of folic acid and pyridoxine hydrochloride (vitamin B6) in healthy individuals. Oral doses of vitamin B6 reduce concentrations of serum folate.

Plasma total homocysteine response was compared in four groups of healthy individuals given orally divided doses of vitamin supplementations for a duration of 5 weeks. The vitamin supplements; A, 0.3 mg folic acid; B, 120 mg vitamin B6; C, combination of 0.3 mg folic acid and 120 mg vitamin B6 or D, 0.6 mg folic acid reduced the concentrations of plasma total homocysteine 20, 17, 32 and 24%, respectively. However, the intergroup comparisons did not show a significant difference in the effects of vitamin supplements. Multivariate analysis with correction for differences in pre-supplement values indicated a significant effect of vitamin B6 supplementation on plasma total homocysteine and serum folate. Our data show that plasma total homocysteine concentrations are reduced with low to medium divided doses of folic acid alone or in combination with vitamin B6.

Administration, Oral↗

[The vitamin A supply of laying hens including during rearing. 2. Effect of varied vitamin A supplementation of mixed feed in rearing on production in the laying period].

In six experiments with laying hybrids the influence of a varied nutritive beta-carotene and vitamin A supply during rearing on the performance in the laying period was tested. Basal rations poor in carotene without vitamin A supplementation in the rearing period diminished feed intake and laying performance in the laying period, retarded the beginning of intensive laying and increased feed expenditure per 100 g egg if the feed for laying hens contained less than 5000 IU vitamin A per kg. Relations between varied vitamin A supply and the performance parameters of the laying performance could not be proved if chick and young hen feed with maize even without vitamin A supplement or if rearing feed with approximately 2500 IU vitamin A or laying hen feed greater than 5000 IU vitamin A supply were used.

Analysis of Variance↗

Response of vitamin B-6 content of muscle to changes in vitamin B-6 intake in men.

Previous reports indicated that in growing rats the vitamin B-6 pool in muscle was relatively stable during deficiency but increased in response to increased vitamin B-6 intake. To determine whether human muscle would show a similar response 10 college-aged males received a low vitamin B-6 diet (1.76 mumol/d) for 6 wk followed by 6 wk on a self-selected diet supplemented with 0.98 mmol pyridoxine HCl/d. During depletion, excretion of pyridoxic acid rapidly adjusted to approximate the intake. Plasma pyridoxal phosphate concentrations at the end of the baseline, depletion, and supplementation periods were 81 +/- 51, 9 +/- 3, and 455 +/- 129 nmol/L, respectively, whereas muscle concentrations were 21 +/- 9, 20 +/- 4, and 25 +/- 7 nmol/g, respectively and total vitamin B-6 in muscle was 28 +/- 10, 27 +/- 4, and 35 +/- 10 nmol/g, respectively. These data provide further confirmation that the vitamin B-6 pools in skeletal muscle are resistant to depletion. They also demonstrate that in humans with constant body weight, vitamin B-6 supplementation is not associated with marked increases in vitamin B-6 in muscle.

Adult↗

Vitamin A supplementation and dietary vitamin A in relation to the risk of xerophthalmia.

We examined the effect of 60-mg (200,000-IU) supplements of vitamin A administered every 6 mo on the incidence of xerophthalmia among preschool children who were free of eye symptoms and signs of vitamin A deficiency. We also prospectively studied the relationship of dietary vitamin A intake with the same endpoint. After 18 mo of follow-up, 400 children developed xerophthalmia during 80,104 child-periods of follow-up. Vitamin A supplementation only modestly reduced the risk of xerophthalmia (relative risk 0.88, 95% confidence interval 0.72-1.07, P = 0.19). On the other hand, total dietary vitamin A intake was strongly associated with reduced risk of xerophthalmia; the multivariate relative risk when children in extreme quintiles were compared was 0.38 (95% confidence interval 0.19-0.74; P for trend over quintiles = 0.002). These results emphasize the need for further data on factors that modify the bioavailability of large-dose vitamin A supplements. Increased consumption of inexpensive vegetables and fruits is highly likely to reduce significantly the risks of vitamin A deficiency, including nutritional blindness in developing countries.

Child↗

Assessment of vitamin A status by the deuterated-retinol-dilution technique and comparison with hepatic vitamin A concentration in Bangladeshi surgical patients.

Hepatic stores of vitamin A were estimated in 31 Bangladeshi surgical patients (15 males and 16 females) by the deuterated-retinol-dilution (DRD) technique and by analysis of the vitamin A concentration of a liver biopsy specimen obtained during previously scheduled abdominal surgery. Patients ranged in age from 21 to 65 y and had an average body mass index (BMI: in kg/m2) of 17.7 +/- 3.4. They received 0.753 mumol [2H4]retinyl acetate/kg body wt orally 9-11 d before surgery. Hepatic vitamin A reserves were estimated according to Furr et al (Am J Clin Nutr 1989;49:713-6) by using a single plasma isotopic-ratio measurement (18-25 d postdose). Estimated mean hepatic vitamin A stores were similar by both techniques, 0.110 +/- 0.072 mmol (by DRD) compared with 0.100 +/- 0.067 mmol (by biopsy). Regression analysis was used to compare results of the DRD and biopsy techniques. A significant linear relation was found between the two techniques (r = 0.75, P < 0.0001), and the least-squares regression line was not significantly different from y = x (P = 0.09). The results indicate that the DRD technique provided a very good estimate of hepatic vitamin A reserves for this population. However, a wide prediction interval was observed for estimates of hepatic vitamin A reserves for individual subjects. Thus, further refinement of the prediction model is necessary to improve estimates of hepatic vitamin A reserves for individual subjects.

Abdomen↗

Dietary calcium and vitamin D intake in elderly women: effect on serum parathyroid hormone and vitamin D metabolites.

In this study, the effect of dietary calcium and vitamin D on serum parathyroid hormone and vitamin D metabolites was measured in 376 free-living women aged 65-77 y. Mean calcium intake in both groups was close to the recommended dietary allowance of 800 mg/d. Mean vitamin D intake in the 245 women not taking vitamin D supplements was 3.53 microg/d (141 IU/d), which is below the recommended dietary allowance of 5 microg/d (200 IU/d). To test the hypothesis that vitamin D is more important than calcium in reducing serum parathyroid hormone, the source of dietary calcium intake was subdivided into milk, which is fortified with vitamin D, and nonmilk sources. The serum parathyroid hormone concentration was inversely correlated with calcium intake derived from milk (r = -0.20, P < 0.01) but not from nonmilk sources (r = -0.06). Furthermore, serum calcidiol correlated with milk calcium intake (r = 0.35, P < 0.001) but not with nonmilk calcium intake (r = 0.10). Multivariate analysis showed a significant effect of season on serum calcidiol but not on serum parathyroid hormone. Serum parathyroid hormone was inversely correlated with serum calcidiol (r = -0.33, P < 0.001) and the regression predicted that mean serum parathyroid hormone would be reduced in the elderly to concentrations considered normal in the young when serum calcidiol is 122 nmol/L (49 ng/mL); this would require a much higher recommended dietary allowance for vitamin D than 5 microg/d (200 IU/d).

Aged↗

Vitamin E, vitamin C, and exercise.

Exercise increases the generation of oxygen free radicals and lipid peroxidation. Strenuous exercise in a person who is unconditioned or unaccustomed to exercise will induce oxidative damage and result in muscle injury. However, aerobic exercise training strengthens the antioxidant defense system by increasing superoxide dismutase. Vitamin C and, especially, vitamin E are shown to decrease the exercise-induced increase in the rate of lipid peroxidation. No ergogenic effects of either vitamin C or E have been shown. Vitamin E was shown to significantly increase circulating neutrophils in older, but not younger, subjects performing eccentric exercise that causes an increase in skeletal muscle damage. In addition to its effect in augmenting the neutrophil response to eccentric exercise, vitamin E causes a greater increase in circulating creatine kinase activity, perhaps indicating increased skeletal muscle repair. Increased vitamin E intake has been associated with enhanced glucose tolerance and insulin action as well as improved lipoprotein status. Future research should examine the combined effects of exercise training and vitamins E and C on these health-related outcomes.

Adult↗

Vitamin C and vitamin E supplement use and bladder cancer mortality in a large cohort of US men and women.

Some epidemiologic studies suggest that use of vitamin C or vitamin E supplements, both potent antioxidants, may reduce the risk of bladder cancer. The authors examined the association between use of individual vitamin C and vitamin E supplements and bladder cancer mortality among 991,522 US adults in the Cancer Prevention Study II (CPS-II) cohort. CPS-II participants completed a self-administered questionnaire at enrollment in 1982 and were followed regarding mortality through 1998. During follow-up, 1,289 bladder cancer deaths occurred (962 in men and 327 in women). Rate ratios were adjusted for age, sex, cigarette smoking, education, and consumption of citrus fruits and vegetables. Regular vitamin C supplement use (>or=15 times per month) was not associated with bladder cancer mortality, regardless of duration (rate ratio (RR) = 0.91, 95% confidence interval (CI): 0.68, 1.20 for <10 years' use; RR = 1.25, 95% CI: 0.91, 1.72 for >or=10 years' use). Regular vitamin E supplement use for >or=10 years was associated with a reduced risk of bladder cancer mortality (RR = 0.60, 95% CI: 0.37, 0.96), but regular use of shorter duration was not (RR = 1.04, 95% CI: 0.77, 1.40). Results support the hypothesis that long-duration vitamin E supplement use may reduce the risk of bladder cancer mortality.

Adult↗

The calcium and vitamin D status in an elderly female population and their response to administered supplemental vitamin D3.

Recent reports have implicated the importance of impaired calcium absorption, inadequate dietary vitamin D, and low serum vitamin D levels in the genesis of metabolic bone diseases in the elderly. This study evaluated the dietary intakes of calcium and Vitamin D, calcium absorption, and serum 25 hydroxycholecalciferol (25 OH D) levels in a population of women (mean age 83 yrs) compared to healthy volunteers (mean age 35 yrs). Dietary intakes of both calcium and vitamin D and serum 25 OH D levels were found to be comparable in both groups. Calcium absorption was normal in the subjects studied and did not change significantly after two 2-week periods of oral supplementation with vitamin D3 in doses of 500 I.U./day and 10,000 I.U./day, although the serum 25 OH D levels rose significantly and comparably in both groups. Thus other etiological factors may play relevant roles in the causation of bone diseases in the elderly and unless deficient dietary or serum vitamin D levels are demonstrated, empirical supplementation with vitamin D should not be undertaken. The differences of the above findings from previously published data are discussed.

Absorption↗

Effect of chronic immobilization stress on tissue distribution of vitamin A in rats fed a diet with adequate vitamin A.

The effect of consecutive daily immobilized stress on the metabolism of vitamin A was studied in rats by following changes in tissue distribution of the vitamin for 14 days. Male rats, fed a diet with adequate vitamin A, were subjected to 4 hours of daily immobilization for 1, 3, 7, 10 or 14 days. Ponderal growth was completely abolished, and serum vitamin A fell markedly. The amount of vitamin A in liver, testes and kidney decreased after the first period of restraint. On the other hand, the amount of vitamin A in adrenal glands increased gradually and reached a maximum (+62.3%) on the 7th day. In conclusion, this experiment showed that daily intermittent immobilization provoked a marked change in distribution of vitamin A in tissues.

Animals↗

Vitamin C nutriture has little short-term effect on vitamin E concentrations in healthy women.

To determine whether the postulated sparing effect of vitamin E by ascorbic acid (AA) is important for human nutrition, we studied vitamin E status in 20 healthy pre-menopausal women (age 20-43 y) with high or low vitamin C intakes for 6 wk in a live-in metabolic unit. The experimental diet contained no fruits and vegetables and provided 5 mg/d of AA (Recommended Dietary Allowance = 60 mg/d), 3 mg/d of alpha-tocopherol (RDA = 10 mg/d) and 42 g/d of tocopherol-stripped safflower oil to increase the vitamin E requirement. Half of the subjects revived a daily AA supplement of 495 mg (high AA group). A biochemical ascorbate deficiency was attained in the low AA group as indicated by plasma AA concentrations that reached the lower limit of normal by study d 15. Oral doses (20 mg) of hexadeuterated RRR-alpha-tocopherol acetate (d6-alphaT) were given daily to all subjects on d 15-21. Measures of vitamin E status included d6-alphaT and unlabeled alpha-tocopherol concentrations in plasma, platelets, buccal cells and adipose. The levels of unlabeled alpha-tocopherol decreased over time in plasma and platelets and were unchanged for buccal cells and adipose, but were not significantly affected by AA intake. Likewise, the rise and fall of plasma and platelet d6-alpha T, and measures of lipid peroxidation, were not affected by AA intake. Although vitamin C nutriture did not significantly affect vitamin E status within the 6-wk time period of this experiment, further study of this question is warranted, because some of the present results indicate a trend toward sparing of tissue tocopherol by high AA intake.

Adipose Tissue↗

Supplementation with vitamin C, vitamin E or beta-carotene influences osmotic fragility and oxidative damage of erythrocytes of zinc-deficient rats.

Dietary zinc deficiency in rats causes increased osmotic fragility of their erythrocytes. In this study, the influence of supplementary antioxidants (vitamin C, vitamin E or beta-carotene) on osmotic fragility, oxidative damage and components of the primary defense system of erythrocytes of zinc-deficient rats was investigated. Indicators of hemolysis in vivo were also examined. Five groups of 12 male rats were force-fed a zinc-adequate diet (control rats), a zinc-deficient diet or a zinc-deficient diet enriched with vitamin C, vitamin E or beta-carotene. Compared with the control rats, the rats fed the zinc-deficient diet without supplementary antioxidants had greater red blood cell osmotic fragility, higher concentrations of thiobarbituric acid-reactive substances and alanine, higher glutathione S-transferase activity, lower concentration of glutathione and activity of glutathione peroxidase as well as lower activity of superoxide dismutase in plasma (P < 0.05). Supplementation with antioxidants generally improved osmotic fragility in zinc-deficient rats without influencing zinc concentration or alkaline phosphatase activity in plasma, indicators of zinc status. At some of the hypotonic saline concentrations tested, vitamin C and beta-carotene significantly affected osmotic fragility. The zinc-deficient rats fed a diet without supplementary antioxidants had significantly higher concentrations of alanine in erythrocytes than the zinc-deficient rats supplemented with vitamin C, vitamin E or beta-carotene and had significantly higher levels of thiobarbituric acid-reactive substances in erythrocytes than the rats supplemented with beta-carotene. There was no indication of hemolysis in vivo in rats fed zinc-deficient diets. The results show that supplementary antioxidants decrease osmotic fragility and oxidative damage of erythrocytes in zinc-deficient rats.

Alanine↗

Weekly vitamin A and iron supplementation during pregnancy increases vitamin A concentration of breast milk but not iron status in Indonesian lactating women.

Studies on the effect of vitamin A and iron supplementation during pregnancy on maternal iron and vitamin A status postpartum are scarce. We investigated whether retinol and iron variables in breast milk and in serum postpartum were enhanced more with weekly vitamin A and iron supplementation during pregnancy than with weekly iron supplementation. During pregnancy, subjects were randomly allocated to two groups and received either (n = 88) a weekly supplement of iron (120 mg Fe as FeSO(4)) and folic acid (500 microg) or (n = 82) the same amount of iron and folic acid plus vitamin A [4800 retinol equivalents (RE)]. Transitional milk (4-7 d postpartum) had higher (P < 0.001) concentrations of retinol and iron than mature milk (3 mo postpartum). Compared with the weekly iron group, the weekly vitamin A and iron group had a greater (P < 0.05) concentration of retinol in transitional milk (as micromol/L) and in mature milk (as micromol/g fat). Although serum retinol concentrations approximately 4 mo postpartum did not differ significantly, the weekly vitamin A and iron group had significantly fewer (P < 0.01) subjects with serum retinol concentrations < or = 0.70 micromol/L than the weekly iron group. Iron status and concentrations of iron in transitional and mature milk did not differ between groups. We have shown that weekly vitamin A and iron supplementation during pregnancy enhanced concentrations of retinol in breast milk although not in serum by approximately 4 mo postpartum. However, no positive effects were observed on iron status and iron concentration in breast milk.

Adolescent↗

Long-term diuretic therapy in hypertensive patients: effects on serum homocysteine, vitamin B6, vitamin B12, and red blood cell folate concentrations.

BACKGROUND: The effects of chronic diuretic use on serum homocysteine and its metabolic cofactors vitamin B6, vitamin B12, and red blood cell (RBC) folate have not been well studied. METHODS: Blood samples from 17 hypertensive patients receiving long-term diuretic therapy and 17 hypertensive patients not taking diuretics were analyzed for serum homocysteine, vitamin B6, vitamin B12, and RBC folate. RESULTS: The mean serum homocysteine concentration for patients taking diuretics (17.87 +/- 1.72 micromol/L) was significantly higher than the mean serum homocysteine concentration for patients not taking diuretics (10.31 +/- 0.99 micromol/L). The mean RBC folate concentration for patients taking diuretics (281.01 +/- 17.56 ng/mL) was significantly lower than the mean RBC folate concentration for patients not taking diuretics (430.85 +/- 28.58 ng/mL). Serum vitamin B6 and vitamin B12 concentrations were not significantly different between the two groups. CONCLUSIONS: Chronic diuretic use is associated with a significant increase in serum homocysteine concentration, a significant decrease in RBC folate concentration, and no significant change in concentrations of vitamins B6 and B12.

Diuretics↗

Vitamin B6, vitamin C, and carpal tunnel syndrome. A cross-sectional study of 441 adults.

As part of an ongoing study of carpal tunnel syndrome (CTS) in industry, we measured plasma concentrations of pyridoxal 5'-phosphate (PLP, a measure of vitamin B6 status) and total ascorbate (ASC, a measure of vitamin C status) in 441 adult volunteers from six industries and a university exercise study. In the entire study group and in non-vitamin users (n = 218), there were no significant differences in mean plasma PLP or ASC concentrations between controls (neither symptoms nor slowing), subjects with symptoms only, subjects with median nerve slowing only, or subjects with CTS (symptoms + slowing). In male non-vitamin users (n = 137), there were significant inverse univariate associations between plasma PLP concentration and the prevalence of pain, the frequency of tingling and nocturnal awakening, and the Phalen test result. In this same subgroup, the ASC/PLP ratio was directly associated with the prevalence of pain and nocturnal awakening, and with the frequency of pain, tingling, and nocturnal awakening. In multivariate analyses, plasma ASC concentration predicted more median nerve slowing and confirmed CTS, and vitamin or vitamin interaction variables were independent predictors of 20 CTS-related outcomes. These multivariate relationships often occurred only after adjustment for age, gender, body mass index, serum alkaline phosphatase activity, or tobacco use. We conclude that there are significant relationships between plasma vitamin levels and both components of CTS (specific symptoms and median nerve slowing). The interaction between plasma PLP and ASC appears to be particularly important with respect to symptoms.

Adult↗

Regulation of renal vitamin D hydroxylase activity in vitamin D deficient rats.

The regulation of renal mitochondrial 1-hydroxylase activity in chronic vitamin D deficiency was studied in male rats. These rats were born of mothers who had been raised from weaning (21 days) on a vitamin D deficient diet and who had no detectable serum 1,25-dihydroxycholecalciferol (1,25-(OH)2D) at the time their offspring were weaned (28 days). In the pups, renal mitochondrial 1-hydroxylase activity was undetectable before the 3rd week of life even though the animals were severely hypocalcemic from birth. The 1-hydroxylase activity first became detectable at 26 days of age, rapidly reached a maximum at day 34, then decreased to become undetectable again by 65 days. Throughout this time serum calcium concentration was less than 5.0 mg/dL and serum parathyroid hormone (PTH) concentration, measured by a midmolecule radioimmunoassay, was two- to five-fold greater than that found in vitamin D replete rats. 1-Hydroxylase activity could be restored in the +65-day-old animals by administration of a single dose of 2.5 micrograms vitamin D3. Enzyme activity was detected within 24 h, was maximal at 72 h, and returned to undetectable levels by 96 h after administration of the vitamin. Serum 1,25-(OH)2D which was undetectable before administration of the vitamin D3, was 108 and 458 pg/mL at 16 and 40 h, respectively, after the injection. The serum concentration of this metabolite then decreased progressively to 80 pg/mL by 6 days. 24-Hydroxylase activity first became detectable 48 h after vitamin D administration, increased to a maximum at 96 h, and thereafter decreased to become undetectable by 7 days.(ABSTRACT TRUNCATED AT 250 WORDS)

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗

Plasma Ca influences vitamin D metabolite levels as rats develop vitamin D deficiency.

The hypocalcemia that accompanies vitamin D deficiency is a major obstacle to proper interpretation of the role(s) of vitamin D metabolites in Ca-sensitive tissues. This paper describes the development and complete characterization of a dietary regimen with which normocalcemia was maintained in rats throughout the development of vitamin D deficiency. Normal weanling rats were fed diets containing 0.8% Ca, 0.5% P, and vitamin D3 (group A), or vitamin D-deficient diets containing 0.8% Ca and 0.5% P (group B); 2.0% Ca and 1.25% P (group C); or 2.0% Ca, 1.25% P, and 20% lactose (group D) for 19 wk. Group D rats were normocalcemic and normophosphatemic with normal parathyroid hormone (PTH) levels throughout the study. In contrast, from 4-19 diet wk, groups B and C were hypocalcemic with elevated PTH. Initially, plasma 25-hydroxyvitamin D3 [25(OH)D3] levels decreased most rapidly, and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] levels decreased least rapidly in group B rats, such that plasma 25(OH)D3 levels were reduced to 200-300 pg/ml before a decrease in 1,25(OH)2D3 levels was observed. However, vitamin D metabolite levels were similar in groups B, C, and D from 4-19 wk. Duodenal active Ca transport mirrored changes in plasma 1,25(OH)2D3 levels and was abolished after 10 wk. The results also suggested that vitamin D may not be necessary for normal bone mineralization since tibia mineral content and plasma alkaline phosphatase levels were similar in normocalcemic groups A and D throughout the study.

Animals↗