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PubMed1982

Synthesis and biological activity of vitamin D2 3 beta-glucosiduronate and vitamin D2 3 beta-sulfate: role of vitamin D2 conjugates in calcium homeostasis.

To ascertain the physiologic function of vitamin D2 conjugates in calcium homeostasis, we synthesized vitamin D2 3 beta-glucosiduronate and vitamin D2 3 beta-sulfate in pure form and tested their biological activity in vitamin D deficient rats fed a low calcium diet. Vitamin D2 3 beta-glucosiduronate was active in promoting calcium transport in the intestine at a dose of 100 pmol per rat. It increased calcium mobilization from bone and soft tissue at a dose of 1000 pmol per rat. This conjugate was less active than equimolar doses of vitamin D2. These results demonstrate that vitamin D2 3 beta-glucosiduronate can be utilized by the rat as a source of vitamin D. In contrast, vitamin D2 3 beta-sulfate was biologically inert. It failed to increase calcium transport in the duodenum of vitamin D deficient rats except at the highest doses tested (greater than 100,000 pmol/rat). It was similarly ineffective in increasing calcium mobilization from bone and soft tissue. Our results lead us to conclude that vitamin D2 3 beta-glucosiduronate is probably utilized by the rat after hydrolysis to the free sterol; on the contrary, the sulfate is not biologically active except at the highest doses tested.

Animals↗
PubMed1985

Effects of different levels of vitamin B-6 supplementation on vitamin B-6 concentrations in human milk and vitamin B-6 intakes of breastfed infants.

Vitamin B-6 has been reported to vary in concentration in human milk in response to changes in maternal intake of the vitamin. This study examined the effects of such changes on the breastfed infants' intake of vitamin B-6. Lactating mothers received 0, 2.5, 10.0 or 20.0 mg pyridoxine X HCl (PN X HCl) for 3 consecutive days in addition to dietary sources. Dietary intakes of vitamin B-6 (mean = 1.8 +/- 0.2 mg/day) were similar among the four groups. Vitamin B-6 was determined in milk samples from each feeding and milk intakes of infants were estimated by test-weighing. Nonsupplemented mothers had lower vitamin B-6 in their milk (93 +/- 8 micrograms/L) and vitamin B-6 intake of their infants was lower (0.06 +/- 0.01 mg/day) compared to other groups. Maternal supplementation with 2.5, 10.0 or 20.0 mg PN X HCl was paralleled by vitamin B-6 levels in milk of 192 +/- 16, 247 +/- 25 and 413 +/- 45 micrograms/L, respectively, and by vitamin B-6 intakes of breastfed infants of 0.12 +/- 0.02, 0.22 +/- 0.02 and 0.28 +/- 0.03 mg/day, respectively. When maternal intakes of vitamin B-6 approximated 20.0 mg/day, breastfed infants were unlikely to receive the current RDA of 0.3 mg vitamin B-6/day.

Adult↗
PubMed2005

High-dose oral vitamin C partially replenishes vitamin C levels in patients with Type 2 diabetes and low vitamin C levels but does not improve endothelial dysfunction or insulin resistance.

Endothelial dysfunction is a hallmark of Type 2 diabetes related to hyperglycemia and oxidative stress. Nitric oxide-dependent vasodilator actions of insulin may augment glucose disposal. Thus endothelial dysfunction may worsen insulin resistance. Intra-arterial administration of vitamin C improves endothelial dysfunction in diabetes. In the present study, we investigated effects of high-dose oral vitamin C to alter endothelial dysfunction and insulin resistance in Type 2 diabetes. Plasma vitamin C levels in 109 diabetic subjects were lower than healthy (36 +/- 2 microM) levels. Thirty-two diabetic subjects with low plasma vitamin C (<40 microM) were subsequently enrolled in a randomized, double-blind, placebo-controlled study of vitamin C (800 mg/day for 4 wk). Insulin sensitivity (determined by glucose clamp) and forearm blood flow in response to ACh, sodium nitroprusside (SNP), or insulin (determined by plethysmography) were assessed before and after 4 wk of treatment. In the placebo group (n = 17 subjects), plasma vitamin C (22 +/- 3 microM), fasting glucose (159 +/- 12 mg/dl), insulin (19 +/- 7 microU/ml), and SI(Clamp) [2.06 +/- 0.29 x 10(-4) dl x kg(-1) x min(-1)/(microU/ml)] did not change significantly after placebo treatment. In the vitamin C group (n = 15 subjects), basal plasma vitamin C (23 +/- 2 microM) increased to 48 +/- 6 microM (P < 0.01) after treatment, but this was significantly less than that expected for healthy subjects (>80 microM). No significant changes in fasting glucose (156 +/- 11 mg/dl), insulin (14 +/- 2 microU/ml), SI(Clamp) [2.71 +/- 0.46 x 10(-4) dl x kg(-1) x min(-1)/(microU/ml)], or forearm blood flow in response to ACh, SNP, or insulin were observed after vitamin C treatment. We conclude that high-dose oral vitamin C therapy, resulting in incomplete replenishment of vitamin C levels, is ineffective at improving endothelial dysfunction and insulin resistance in Type 2 diabetes.

Administration, Oral↗
PubMed1995

Effects of vitamin B12, folate, and vitamin B6 supplements in elderly people with normal serum vitamin concentrations.

In a prospective, multicentre, double-blind controlled study, the effect of an intramuscular vitamin supplement containing 1 mg vitamin B12, 1.1 mg folate, and 5 mg vitamin B6 on serum concentrations of methylmalonic acid (MMA), homocysteine (HCYS), 2-methylcitric acid (2-MCA), and cystathionine (CYSTA) was compared with that of placebo in 175 elderly subjects living at home and 110 in hospital. Vitamin supplement and placebo were administered eight times over a 3-week period. Vitamin supplement but not placebo significantly reduced all four metabolite concentrations at the end of the study in both study groups. The maximum effects of treatment were usually seen within 5-12 days. Initially elevated metabolite concentrations returned to normal in a higher proportion of the vitamin than of the placebo group: 92% vs 20% for HYCS; 82% vs 20% for MMA; 62% vs 25% for 2-MCA; and 42% vs 25% for CYSTA. The response rate to vitamin supplements supports the notion that metabolic evidence of vitamin deficiency is common in the elderly, even in the presence of normal serum vitamin levels. Metabolite assays permit identification of elderly subjects who may benefit from vitamin supplements.

Aged↗
PubMed1980

The effects of vitamin C, vitamin B6, vitamin B12, folic acid, riboflavin, and thiamin on the breast milk and maternal status of well-nourished women at 6 months postpartum.

The effects of vitamin supplements and/or diet on the vitamin levels in milk of women were determined at 6 months postpartum. Six subjects consumed a daily supplement (Natalins, Mead-Johnson) in addition to a well-balanced diet--supplemented group, and six subjects consumed only a well-balanced diet--nonsupplemented group. The subjects expressed milk for 3 days at 4-hr intervals, 0, 4, 8, and 12 hr after awakening or taking their vitamin supplement. A 4-day diet record, fasting blood sample, and 24-hr urine samples were collected on each subject at 6 months postpartum. Nutrient intake from diet alone did not differ significantly between the two groups except for riboflavin intake which was significantly higher in the supplemented group. The nutritional status of all women indicated excellent dietary intakes, which vitamin supplementation did not alter significantly. Milk concentration of vitamin B6, vitamin B12, folate, thiamin, riboflavin, and vitamin C, did not differ significntly between groups. Thiamin, vitamin B12, and vitamin B6 concentration in the milk did appear to plateau during the day. Vitamin supplementatin at 6 months postpartum did not affect the breast milk concentration or the nutritional status of well-nourished women.

Ascorbic Acid↗
PubMed1989

Relationship of vitamin A and vitamin E intake to fasting plasma retinol, retinol-binding protein, retinyl esters, carotene, alpha-tocopherol, and cholesterol among elderly people and young adults: increased plasma retinyl esters among vitamin A-supplement users.

We studied the relationships of supplemental and total vitamin A and supplemental vitamin E intake with fasting plasma biochemical indicators of vitamin A and vitamin E nutritional status among 562 healthy elderly people (aged 60-98 y) and 194 healthy young adult (aged 19-59 y) volunteers. All subjects were nonsmokers. For the young adults, plasma retinol was significantly greater in males than in females (p less than 0.01); retinol was not related to supplemental vitamin A intake for either group. Fasting plasma retinyl esters demonstrated a significant increase with vitamin A supplement use. For supplemental vitamin A intakes of 5001-10,000 IU/d, a 2.5-fold increase over nonusers in fasting plasma retinyl esters was observed for elderly people (p less than 0.05) and a 1.5-fold increase for young adults (p greater than 0.20). For elderly people, greater fasting plasma retinyl esters were associated with long-term vitamin A supplement use (greater than 5 y) and biochemical evidence of liver damage. Elderly people who take vitamin A supplements may be at increased risk for vitamin A overload.

Aged↗
PubMed1999

Dietary vitamin E and beta-carotene sources influence vitamin A and E storage in young rats fed marginal and adequate vitamin E.

The effects of two vitamin E levels (30 and 75 IU/kg diet) and the interrelation of two vitamin E sources [dl-alpha-tocopheryl acetate (dl-alpha-TA) and d-alpha-tocopheryl acid succinate (d-alpha-TAS)] and three vitamin A sources [retinyl palmitate (RP), all-trans synthetic beta-carotene (SBC), and natural beta-carotene (NBC)] were studied. Dietary vitamin A sources provided 4,000 IU/kg. Twelve groups of Fischer 344 rats (10/group) were fed designated diets for eight weeks. For RP, SBC, and NBC, the increase in each vitamin E source from a marginal to an adequate dietary level caused a significant increase in liver and heart alpha-tocopherol. Among rats fed diets with an adequate level of vitamin E, d-alpha-TAS was not as effective as dl-alpha-TA in increasing liver alpha-tocopherol levels. Plasma retinol was lower in rats fed d-alpha-TAS than in those fed dl-alpha-TA. Among rats fed diets with an adequate level of dl-alpha-TA, those fed SBC had significantly higher liver and heart alpha-tocopherol concentrations than did all other groups (p < 0.05). Liver retinol equivalents for rats fed NBC were approximately 66% lower than those in rats fed SBC or RP (p < 0.05). The roles of the two vitamin E sources in alpha-tocopherol metabolism are not equivalent. These data indicate that vitamin A source influences the magnitude of the tissue vitamin A and E changes in response to the two vitamin E sources.

Animals↗
PubMed1988

Vitamin concentrations in very low birth weight infants given vitamins intravenously in a lipid emulsion: measurement of vitamins A, D, and E and riboflavin.

Because total parenteral nutrition with vitamins added to the glucose-amino acid mixture is often associated with a reduction in blood levels of vitamin A (retinol) during the routine treatment of many very low birth weight (VLBW) infants (less than 1500 gm), and because retinol losses in the plastic delivery system can be prevented by adding the vitamins to an intravenous lipid emulsion, seven VLBW infants with a mean birth weight of 900 gm (range 450 to 1360 gm) were given 40% of a unit dose vial, per kilogram of body weight, of a multivitamin preparation (M.V.I. Pediatric) (280 micrograms retinol; 160 IU vitamin D; 2.8 mg tocopherol; 0.68 mg riboflavin) in a lipid emulsion, Intralipid. After treatment with the intralipid-vitamin mixture for 19 to 28 days, plasma vitamin A (retinol) concentrations increased significantly from 11.0 +/- 0.76 (mean +/- SEM) before intralipid to 19.2 +/- 0.97 micrograms/dl after the intralipid-vitamin mixture (p less than 0.01); 25-hydroxyvitamin D concentrations increased from an initial value of 12.6 +/- 2.6 to 20.2 +/- 1.9 mg/dl (p less than 0.01); alpha-tocopherol concentrations increased from an initial value of 0.31 +/- 0.06 to 2.44 +/- 0.13 mg/dl (p less than 0.01); and riboflavin levels increased from 64.1 +/- 7.8 ng/ml to concentrations between 20 and 100 times the initial level. Erythrocyte riboflavin levels increased from 71.8 +/- 14 initially to 166 +/- 41 ng/gm hemoglobin, and erythrocyte flavin-adenine dinucleotide levels increased similarly from 972 +/- 112 initially to 2005 +/- 294 ng/gm hemoglobin. These results show that the addition of M.V.I. Pediatric to Intralipid decreases the extensive in vivo loss of retinol and is associated with an increase in plasma retinol concentrations in VLBW infants. The daily doses of vitamins D (160 IU/kg) and E (2.8 mg/kg) appear sufficient, but the dose of vitamin A (280 micrograms/kg) is insufficient to raise blood levels of all infants into the normal range. The current dose of riboflavin is excessive and may be harmful.

Erythrocytes↗
PubMed1988

The vitamin A activity of beta-carotene in growing pigs. 1. Effect of a supplementation of a grain soya bean meal diet with vitamin A or beta-carotene on the liver vitamin A storage.

In 3 experiments with a total of 113 growing pigs, supplements of 1,000 to 9,000 IU vitamin A or 2 to 100 mg beta-carotene to vitamin A and beta-carotene free grains soyabean-meal-diets were tested. The liver samples were taken by biopsy or after slaughtering. The error of biopsy sampling was defined in preliminary experiments. The initial liver vitamin A depots were checked by slaughtering of 5 piglets of each group. The vitamin A content was analyzed by the anhydromethod or fluorometrically. In all 3 experiments, the different vitamin or provitamin intake did not influence feed intake and growth at any time. Highly significant linear relations were found between the intake of vitamin A or beta-carotene and the storage in the liver. Due to the higher relative liver weight, younger animals had a lower vitamin A concentration in this organ. Related to the tested beta-carotene dose of 2, 4, 8, 50 and 100 mg/kg feed, a vitamin A activity of 360, 320, 290, 130 and 80 micrograms retinol equivalents per mg beta-carotene was found. The conversion of beta-carotene into vitamin A decreases inversely to the beta-carotene intake. The vitamin A activity of synthetic beta-carotene which is higher than the beta-carotene analyzed in feedstuffs is discussed.

Animal Feed↗
PubMed1979

The effects of vitamin C, vitamin B6, and vitamin B12 supplementation on the breast milk and maternal status of well-nourished women.

The effects of vitamin supplements and/or diet on the levels of vitamin C, vitamin B6, and vitamin B12 in milk and blood of lactating women were determined. At the end of gestation, subjects were divided into two lactation groups: supplemented (10 subjects) and nonsupplemented (seven subjects). Milk samples were collected from 5 to 7 days and 43 to 45 days postpartum. Fasting blood samples were drawn at 8 and 46 days postpartum for vitamin C, B6, and B12 status measurements. Dietary records of all foods consumed by the subject were kept for 4 days at 1 and 6 weeks postpartum. The vitamin B6 level in breast milk of the unsupplemented group of mothers was significantly lower (P less than 0.05) than the supplemented group of women at 5 to 7 days postpartum. Vitamin B12 concentration in milk of nonsupplemented mothers at 43 to 45 days postpartum was significantly lower (P less than 0.05) than the supplemented group of women at 43 to 45 days postpartum. None of the milk values or the maternal blood levels measured in the women was less than published norms for vitamin C, vitamin B6, and vitamin B12.

Ascorbic Acid↗
PubMed1985

Demonstration that the vitamin D metabolite 1,25(OH)2-vitamin D3 and not 24R,25(OH)2-vitamin D3 is essential for normal insulin secretion in the perfused rat pancreas.

It has previously been shown that vitamin D deficiency impairs arginine-induced insulin secretion from the isolated, perfused rat pancreas (Science 1980; 209:823-25). Since vitamin D is known to be metabolized to 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) and 24R,25-dihydroxyvitamin D3 (24,25[OH]2D3), it is essential to clarify which vitamin D metabolite has the important role of enhancing insulin secretion. In this report, a comparison is made of the relative efficacy of 3-wk repletion with vitamin D3 (980 pmol/day), 1,25(OH)2D3 (39 pmol/day or 195 pmol/day), and 24,25(OH)2D3 (650 pmol/day) on arginine-induced insulin secretion from the isolated, perfused rat pancreas; in this experiment, the daily caloric intake of the animals receiving vitamin D or its metabolites was controlled by pair feeding to the caloric intake of the vitamin D-deficient rats. 1,25(OH)2D3 repletion was found to completely restore insulin secretion to the levels seen in vitamin D3-replete, pair-fed controls in both the first and second phases, while 24R,25(OH)2D3 only partially improved insulin secretion, and then only in the first phase. Changes of both serum calcium levels and dietary caloric intake after vitamin D metabolite administration are concluded to play a lesser role on the enhancement of insulin secretion, since, in a separate experiment, vitamin D-deficient rats with normal serum calcium levels did not show recovery of insulin secretion equivalent to the vitamin D-replete animals under conditions of dietary pair feeding. These results suggest that 1,25(OH)2D3 but not 24,25(OH)2D3 plays an essential role in the normal insulin secretion irrespective of the dietary caloric intake and prevailing serum calcium levels.

24,25-Dihydroxyvitamin D 3↗
PubMed2000

Antioxidant vitamin and mineral supplements for age-related macular degeneration.

BACKGROUND: It has been proposed that antioxidants may prevent cellular damage in the retina by reacting with free radicals produced in the process of light absorption. OBJECTIVES: The objective of this review is to assess the effects of antioxidant vitamin and/or mineral supplementation on the progression of age-related macular degeneration. SEARCH STRATEGY: The Cochrane Eyes and Vision Group specialised registered, the Cochrane Controlled Trials Register - Central, MEDLINE, the Science Citation Index, and the reference lists of relevant articles were searched. Investigators of included studies were contacted. The most recent searches were performed in December 1999. SELECTION CRITERIA: All randomised trials comparing an antioxidant vitamin and/or mineral supplement (alone or in combination) to control in people with age-related macular degeneration were included. DATA COLLECTION AND ANALYSIS: The reviewer extracted data and assessed trial quality. Due to the small number of trials identified, and variable methods of collecting and presenting outcome data, no statistical summary measure was calculated. MAIN RESULTS: Four published, two unpublished and two ongoing trials were identified. Published trials to date have been small and results inconsistent. Adverse effects and quality of life for people with age-related macular degeneration have not been addressed. REVIEWER'S CONCLUSIONS: The question as to whether people with age-related macular degeneration should take antioxidant vitamin or mineral supplements to prevent progression of the disease has not been answered by research to date. The results of ongoing trials are awaited.

Antioxidants↗
PubMed2001

Comparison of antioxidant efficacy of vitamin E, vitamin C, vitamin A and fruits in coronary heart disease: a controlled trial.

OBJECTIVE: To determine the efficacy of various antioxidant vitamins and a major dietary source of antioxidants (fruits) we performed a randomized controlled trial. METHODS: 175 successive patients with coronary heart disease (CHD) presenting to our centre were recruited and using a Latin-square design divided into five groups of 35 each. The groups were matched for age, lifestyle and dietary variables, clinical diagnosis and drug treatment status. None of the patients was on lipid-lowering drugs. Supplemental vitamins were stopped for one month before study began and American Heart Association Step II dietary advice was given to all. At baseline, total cholesterol, triglycerides, HDL and LDL cholesterol and lipid peroxide measured as thiobarbaturic acid reactive substances (TBARS) were determined. Group I received placebo capsules; Group II vitamin E 400 units/day; Group III vitamin C 1,000 mg; Group IV vitamin A 25,000 IU; Group V received 400 gm of fruit daily. Lipids and lipid peroxide levels were determined at 30 days follow-up. RESULTS: Response rate in various groups varied form 86% to 91%. No significant changes in total, HDL, LDL cholesterol and triglyceride levels were seen in Groups I, II, III and IV (paired t-test p > 0.05). In Group V there was a significant decrease in total cholesterol (-7.8 +/- 11.1%), and LDL cholesterol (-11.2 +/- 25.4%) and increase in HDL cholesterol (+12.9 +/- 20.1%) (paired t-test p < 0.01). Lipid peroxide levels decreased significantly in all the treatment groups (p < 0.01). This decrease was the highest in Group II (vitamin E; -36.4 +/- 17.7%) as compared to Group III (vitamin C -19.8 -/+ 10.8%); Group IV (vitamin A -5.4 +/- 17%) and Group V (fruits -13.1 +/- 12.0%). CONCLUSIONS: All the antioxidant vitamins and fruits significantly decrease lipid peroxide levels and oxidant load in CHD patients. However, fruits are the best choice as they also favourably modify the lipid profile.

Antioxidants↗
PubMed1993

The effect of formula versus breast feeding and exogenous vitamin K1 supplementation on circulating levels of vitamin K1 and vitamin K-dependent clotting factors in newborns.

The influence of breast or formula feeding together with that of a single supplementation of vitamin K1 at birth, on the vitamin K1 level and vitamin K-dependent clotting factors were studied in 65 breast and 15 formula fed infants. All breast fed newborns without supplementation (n = 25) had very low serum vitamin K1 at weeks 1 and 6. Oral vitamin K supplementation (n = 22) or i.m. (n = 18) at birth resulted in high serum levels at week 1, while at week 6 the effect had disappeared. Formula fed infants had vitamin K1 values within the normal adult range at all study points. The low serum levels of vitamin K1 were not associated with haemorrhagic disorders or coagulation abnormalities. The mean values of vitamin K1 in maternal sera at weeks 1 and 6 were 2.3 nmol/l and 1.8 nmol/l and in breast milk 2.7 nmol/l and 2.0 nmol/l respectively. No correlation existed between the values in breast milk and maternal serum. To maintain serum levels of vitamin K1 within the adult physiological range, repeated administration of low doses is needed in breast fed newborns beyond 1 week of age.

Breast Feeding↗
PubMed1995

The effect of excessive dietary vitamin A on performance and vitamin E status in swine fed diets varying in dietary vitamin E.

A study was conducted to evaluate the effects of high dietary vitamin A on vitamin E status and performance of growing-finishing pigs fed diets supplemented with varying levels of vitamin E. Treatments consisted of corn-soybean meal-based diets supplemented with retinyl acetate to provide 2,000 or 20,000 IU of vitamin A/kg of diet and with DL-alpha-tocopheryl acetate to provide 0, 15, or 150 IU of added vitamin E/kg in a 2 x 3 factorial arrangement. The trial involved 84 crossbred pigs (26 kg initial BW) allotted to pens of two pigs each (one gilt, one barrow). Serum was obtained from all pigs on d 0, 3, 7, 21, 35, 63, and 77 of the 83- or 90-d feeding period. Tissue samples (liver, leg, and neck muscle, backfat, and leaf fat) were collected from one pig (barrow) in each pen at the end of the feeding period. Average daily gain and gain:feed were .93 kg and .30, respectively, without treatment differences (P > .10). Serum alpha-tocopherol increased linearly (P < .01) by d 3 with increasing level of dietary vitamin E supplementation. High dietary vitamin A resulted in a small decrease (P < .01) in serum alpha-tocopherol on d 3, but serum alpha-tocopherol concentration was not affected (P > .10) on other days. Tissue alpha-tocopherol increased linearly (P < .001) as dietary vitamin E increased in all tissues examined. No consistent evidence was found to indicate that a high level of dietary vitamin A interfered with performance or with blood serum or tissue alpha-tocopherol concentrations in growing-finishing swine.

Animal Feed↗