A randomized, placebo-controlled trial of vitamin D supplementation to improve glycaemia in overweight and obese African Americans.

AIMS: Vitamin D deficiency may increase the risk for type 2 diabetes. African Americans tend to have poor vitamin D status and increased risk of diabetes, but effects of vitamin D supplementation on components of diabetes risk have not been tested in this group. This study was conducted to determine whether vitamin D supplementation improves insulin secretion, insulin sensitivity and glycaemia in African Americans with prediabetes or early diabetes. METHODS: In this randomized, placebo-controlled trial, we examined the effect of 4000 IU/day vitamin D(3,) on glycaemia and contributing measures including insulin secretion, insulin sensitivity and the disposition index over 12 weeks in 89 overweight or obese African Americans with prediabetes or early diabetes. Outcome measures were derived from oral glucose tolerance testing. RESULTS: Mean plasma 25-hydroxyvitamin D was about 40 nmol/l in the placebo and vitamin D groups at baseline and increased to 81 nmol/l with supplementation. Insulin sensitivity decreased by 4% in the vitamin D group compared with a 12% increase in the placebo group (p = 0.034). Insulin secretion increased by 12% in the vitamin D group compared with a 2% increase in the placebo group (p = 0.024), but changes in the disposition index were similar across groups. There was no effect of supplementation on post-load glucose or other measures of glycaemia. CONCLUSIONS: Supplementation with 4000 IU/day vitamin D(3) successfully corrected vitamin D insufficiency and had divergent effects on insulin secretion and sensitivity with no overall effect on disposition index or glycaemia. In this study, vitamin D supplementation for 3 months did not change the pathophysiology of prediabetes in overweight and obese African Americans.

Activation of the calcium sensing receptor stimulates gastrin and gastric acid secretion in healthy participants.

UNLABELLED: In 17 adults on a fixed metabolic diet, an 11-day course of cinacalcet increased serum gastrin and basal gastric acid output, but not maximal gastric acid output, compared with a placebo. These findings indicate that the calcium sensor receptor plays a role in the regulation of gastric acid. INTRODUCTION: Gastric acid secretion is a complex process regulated by neuronal and hormonal pathways. Ex vivo studies in human gastric tissues indicate that the calcium sensing receptor (CaR), expressed on the surface of G and parietal cells, may be involved in this regulation. We sought to determine whether cinacalcet, a CaR allosteric agonist, increases serum gastrin and gastric acid secretion. METHODS: Seventeen healthy adults with normal gastric acid output were placed on an 18-day metabolic diet. On day 8 (baseline), participants were given cinacalcet (15 then 30 mg/day) or placebo for 11 days. Changes in gastric acid output, serum gastrin, and other measures were compared in the two groups. RESULTS: Changes in serum gastrin and basal acid output (adjusted for baseline body weight) were significantly more positive in the cinacalcet group compared with placebo (P = 0.004 and P = 0.039 respectively). Change in maximal acid output was similar in the two groups (P = 0.995). As expected, cinacalcet produced significant decreases in serum PTH (P < 0.001) and ionized calcium levels (P = 0.032), and increases in serum phosphorus levels (P = 0.001) and urinary calcium (P = 0.023). CONCLUSIONS: This study provides in vivo evidence that activation of the CaR increases serum gastrin levels and basal gastric acid secretion in healthy adults.

Calcium supplement and bone medication use in a US Medicare health maintenance organization.

This study was conducted to determine the prevalence of the use of calcium supplements and of prescription medications to prevent or treat osteoporosis in men and women in a large New England Medicare Health Maintenance Organization (HMO). A two-page diet, medication use and medical history questionnaire was sent to a random sample of 9000 out of 82 985 members and 2932 (32.6%) responded. Over 97% of the participants were Caucasian and 64.7% were female. The mean ages of the men and women were 74.4+/-5.8 and 74.6+/-6.2 years, respectively. Sixty-nine percent of the men and 59% of the women consumed two or fewer servings of dairy foods per day. Calcium supplement use was more prevalent among the women than the men (66.8% vs 24.9%, p<0.001). Men and women with higher dairy food intakes were more likely to take calcium supplements than were those with lower dairy intakes. Prescription bone medications (including bisphosphonates, raloxifene and calcitonin) were used currently by 17.5% of the women and 2.3% of the men ( p<0.001). An additional 16.2% of the women currently took estrogen. Among the women, bone medication use did not change with age but estrogen use declined with increasing age. Among women age 80+ years, 15.6% used bone medications and 4.9% took estrogen. According to a national survey, more than half the US Caucasian female population over age 80 years has bone density low enough to warrant treatment under current guidelines. Based on the results of this survey, many elderly men and women may benefit from increased utilization of calcium supplements and bone-active medications.

Calcium and vitamin D supplements reduce tooth loss in the elderly.

PURPOSE: Oral bone and tooth loss are correlated with bone loss at nonoral sites. Calcium and vitamin D supplementation slow the rate of bone loss from various skeletal sites, but it is not known if intake of these nutrients affects oral bone and, in turn, tooth retention. SUBJECTS AND METHODS: Tooth loss was examined in 145 healthy subjects aged 65 years and older who completed a 3-year, randomized, placebo-controlled trial of the effect of calcium and vitamin D supplementation on bone loss from the hip, as well as a 2-year follow-up study after discontinuation of study supplements. Teeth were counted at 18 months and 5 years. A comprehensive oral examination at 5 years included assessment of caries, oral hygiene, and periodontal disease. The odds ratio (OR) and 95% confidence interval (CI) of tooth loss were estimated by stepwise multivariate logistic regression. Initial age (mean +/- SD) of subjects was 71 +/- 5 years, and the number of teeth remaining was 22 +/- 7. RESULTS: During the randomized trial, 11 of the 82 subjects (13%) taking supplements and 17 of the 63 subjects (27%) taking placebo lost one or more teeth (OR = 0.4; 95% CI: 0.2 to 0.9). During the 2-year follow-up period, 31 of the 77 subjects (40%) with total calcium intake of at least 1000 mg per day lost one or more teeth compared with 40 of the 68 subjects (59%) who consumed less (OR = 0.5; 95% CI: 0.2 to 0.9). CONCLUSION: These findings suggest that intake levels of calcium and vitamin D aimed at preventing osteoporosis have a beneficial effect on tooth retention.

Vitamin D status of an outpatient clinic population.

Vitamin D insufficiency contributes to bone loss and fracture risk. Low 25-hydroxyvitamin D (25OHD) levels are common in elderly people and in housebound and hospitalized patients. This study was conducted to assess wintertime 25OHD levels in relation to self-reported vitamin D supplement use in an outpatient thyroid clinic population. We assessed the medical history, vitamin D intake from milk and supplements, and serum 25OHD levels in 231 women and 41 men who attended a Thyroid Clinic between January and March, 1999. Of the 272 outpatients, 13.6% had 25OHD levels <40 nmol/l and 53.3% had levels below 80 nmol/l. Fewer than 15% of the patients consumed more than 200 IU per day of vitamin D from milk. Vitamin D supplement use was a positive determinant of serum 25OHD concentration (P < 0.001). For example, among the largest homogenous subset of patients, Caucasian women (n = 137), 30% of the unsupplemented women, and 65% of those taking 400 lU/day of vitamin D had levels of 25OHD as high as 80 nmol/l. Other significant determinants of 25OHD levels were race, weight, milk intake, and recent southern travel. Thyroid disorder, serum TSH level, and age were not predictors of serum 25OHD concentration. In conclusion, at their current dietary vitamin D intake levels, most patients at this latitude will need vitamin D supplements in the wintertime.

Effect of withdrawal of calcium and vitamin D supplements on bone mass in elderly men and women.

BACKGROUND: Supplementation with calcium and vitamin D reduces bone loss and prevents fractures in elderly people, but it is not known whether any lasting benefit remains if the supplements are discontinued. OBJECTIVE: The objective was to determine whether gains in bone mineral density (BMD) induced by calcium and vitamin D supplementation persist after supplement withdrawal. DESIGN: Two-hundred ninety-five healthy, elderly men and women (aged >/=68 y) who had completed a 3-y randomized, placebo-controlled trial of calcium and vitamin D supplementation were followed for an additional 2 y during which no study supplements were given. BMD was measured by dual-energy X-ray absorptiometry, and biochemical variables related to calcium metabolism and bone turnover were measured. RESULTS: In the 128 men, supplement-induced increases in spinal and femoral neck BMD were lost within 2 y of supplement discontinuation, but small benefits in total-body BMD remained. In the 167 women, there were no lasting benefits in total-body BMD or at any bone site. Consistent with the observations on BMD, the bone turnover rates in both men and women (as measured by serum osteocalcin concentrations) returned to their original higher concentrations within the same 2-y period. CONCLUSION: Discontinued calcium and vitamin D supplementation has limited cumulative effect on bone mass in men and women aged >/=68 y.

Associations of the collagen type Ialpha1 Sp1 polymorphism with five-year rates of bone loss in older adults.

The collagen type Ialpha1 Sp1 (ColIA1) polymorphism has been associated with reduced bone mineral density (BMD) and increased prevalence of osteoporosis. This study examines associations of the ColIA1 genotype with BMD and 5-year rates of change in BMD in elderly men and women. The 243 subjects, aged 65 years and older, were participants in two consecutive studies lasting a total of 5-years. BMD of the total body, femoral neck, and lumbar spine were made by dual-energy X-ray absorptiometry (DXA). The distribution of the genotypes (155 in the SS genotype, 79 in Ss, and 9 in ss) was proportionately similar to those reported by others. Baseline BMD did not differ significantly at any skeletal site. Unadjusted 5-year percent changes in BMD differed significantly by genotype only at the total body (P = 0.009), where the change was -0.29+/-0.21 (SEM) in the SS genotype, -0.60+/-0.25 in the Ss genotype, and -3.01+/-0.72 in the ss genotype. This 9.4% increase in bone loss of the ss genotype relative to the SS genotype was reduced to an 8.9% increase after adjustment for sex, age, weight, and supplementation group. Results at the femoral neck were directionally similar, but not statistically significant. No effect of genotype on change in spine BMD was observed. In conclusion, bone loss from the total body was significantly greater in elderly men and women who were homozygous for the s allele compared with heterozygotes and SS homozygotes. This finding suggests a possible explanation for the association of the ColIA1 polymorphism with increased rates of osteoporotic fracture, but should be interpreted with caution because of the small number of subjects in the unfavorable ss genotype.

Plasma 25-hydroxyvitamin D responses of younger and older men to three weeks of supplementation with 1800 IU/day of vitamin D.

OBJECTIVE: The objective of this study was to compare changes in plasma 25-hydroxyvitamin D (25(OH)D) levels of younger and older men after three weeks of oral vitamin D supplementation. METHODS: Nine younger men (22 to 28 years) and nine older men (65 to 73 years) with self-reported vitamin D intakes below 200 IU/d were enrolled in February and randomized to 1800 IU/d of ergocalciferol (vitamin D2, n=11) or to a control group (n=7) and followed for three weeks. Blood was collected at baseline, and after one, two and three weeks for measurement of plasma concentrations of total 25(OH)D, 25(OH)D2 and 25(OH)D3. RESULTS: In both the younger and older supplemented men, 25(OH)D2 and total 25(OH)D concentrations increased significantly during the study, whereas values of these metabolites did not change in younger or older control subjects. No group showed significant changes in 25-hydroxyvitamin D3. There was a significant interaction between age group and supplement group, suggesting that the effect of vitamin D2 supplementation on changes in 25(OH)D2 changes with age. The mean increase in 25(OH)D2 was greater in the younger supplemented men than in the older supplemented men (37+/-9 nmol/L vs. 19.5 nmol/L, p=0.027), and this accounted for their significantly greater increase in total 25(OH)D. CONCLUSION: These data are consistent with an age-related decline in the absorption, transport or liver hydroxylation of orally-consumed vitamin D.

The association of oral contraceptive use with plasma 25-hydroxyvitamin D levels.

OBJECTIVE: This analysis was conducted to compare wintertime 25-hydroxyvitamin D (25OHD) levels of young women who did and did not use oral contraceptives (OC). METHODS: The subjects were 66 Caucasian women aged 20 through 40 recruited from the Boston area. Plasma 25OHD was measured in February or March and again 1 year later. Other measurements included height, weight and vitamin D intake from diet and supplements. RESULTS: The initial mean 25OHD level of the 26 OC users was 41% higher than those of nonusers before adjustment for age and vitamin D intake (83 +/- 40 (sd) nmol/L compared with 59 +/- 22), and 39% higher after adjustment (p = 0.003). Five women who discontinued OC use during the year following their initial measurement all had decreases in their 25OHD levels (mean change was -25.5 +/- 17.7 (SD) nmol/L), whereas levels in women whose OC use or non-use was constant did not change. CONCLUSION: OC use increases circulating levels of 25OHD, and should be considered when interpreting values obtained for clinical evaluation or nutrition research.

PIP: This study was conducted to compare wintertime hyroxyvitamin D (250HD) levels among 66 young Caucasian women between ages 20 and 40 years from the Boston area who did and did not take oral contraceptives (OCs). Plasma 250HD was measured within a 2-month period and again after 1 year. Other measurements taken were height, weight, and intake of vitamin D from diet and supplements. The study demonstrated that the 250 HD levels of women who use OCs were as much as 24.1 nmol/l higher than those of non-OC users. This 41% difference decreased to 39% after adjustment for age and intake of vitamin D. All 5 women who discontinued OC use in the year after their initial measurement had reduced 250HD levels, while levels in the women whose OC use or non-use was constant remained unchanged throughout the study period. There were no significant associations between 250HD levels and ethinyl estradiol dosage, type of OC, or duration of use. In conclusion, OC use increases the circulating levels of 250HD of premenopausal adult women and should be taken into consideration when interpreting values obtained for clinical evaluation or nutrition research.

Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older.

BACKGROUND: Inadequate dietary intake of calcium and vitamin D may contribute to the high prevalence of osteoporosis among older persons. METHODS: We studied the effects of three years of dietary supplementation with calcium and vitamin D on bone mineral density, biochemical measures of bone metabolism, and the incidence of nonvertebral fractures in 176 men and 213 women 65 years of age or older who were living at home. They received either 500 mg of calcium plus 700 IU of vitamin D3 (cholecalciferol) per day or placebo. Bone mineral density was measured by dual-energy x-ray absorptiometry, blood and urine were analyzed every six months, and cases of nonvertebral fracture were ascertained by means of interviews and verified with use of hospital records. RESULTS: The mean (+/-SD) changes in bone mineral density in the calcium-vitamin D and placebo groups were as follows: femoral neck, +0.50+/-4.80 and -0.70+/-5.03 percent, respectively (P=0.02); spine,+2.12+/-4.06 and +1.22+/-4.25 percent (P=0.04); and total body, +0.06+/-1.83 and -1.09+/-1.71 percent (P<0.001). The difference between the calcium-vitamin D and placebo groups was significant at all skeletal sites after one year, but it was significant only for total-body bone mineral density in the second and third years. Of 37 subjects who had nonvertebral fractures, 26 were in the placebo group and 11 were in the calcium-vitamin D group (P=0.02). CONCLUSIONS: In men and women 65 years of age or older who are living in the community, dietary supplementation with calcium and vitamin D moderately reduced bone loss measured in the femoral neck, spine, and total body over the three-year study period and reduced the incidence of nonvertebral fractures.

Rates of bone loss in postmenopausal women randomly assigned to one of two dosages of vitamin D.

We conducted a study to determine whether increasing vitamin D intake above the recommended dietary allowance (RDA) of 5.0 micrograms (200 IU)/d reduces bone loss in healthy postmenopausal women residing at latitude 42 degrees N. In this double-blind, randomized 2-y trial, we enrolled 247 healthy ambulatory postmenopausal women who consumed an average of 2.5 micrograms (100 IU) vitamin D/d in their usual diets. The women were given either 2.5 micrograms (100 IU) or 17.5 micrograms (700 IU) vitamin D/d. All women received 500 mg supplemental calcium per day as citrate malate. Duplicate hip and spine and single whole-body scans were performed by dual-energy x-ray absorptiometry at 6-mo intervals selected to flank the periods when 25-hydroxycholecalciferol (calcidiol) concentrations are highest (summer/fall) and lowest (winter/spring). Plasma calcidiol and serum osteocalcin were measured in these seasons in year 1. Both treatment groups lost bone mineral density from the femoral neck, but the 17.5-micrograms group lost less than (-1.06 +/- 0.34%; mean +/- SE) the 2.5-micrograms group (-2.54 +/- 0.37%, P = 0.003). Seventy percent of the benefit each year occurred in winter/spring and 30% in summer/fall. Changes in spinal and whole-body bone densities did not differ by treatment group and were minimal after 2 y. Serum osteocalcin and plasma calcidiol (2.5-micrograms group only) fluctuated with season. In conclusion, in healthy, calcium-supplemented, postmenopausal women residing at latitude 42 degrees N, an intake of 5.0 micrograms (200 IU) vitamin D/d is sufficient to limit bone loss from the spine and whole body but it is not adequate to minimize bone loss from the femoral neck.(ABSTRACT TRUNCATED AT 250 WORDS)

Caffeine and bone loss in healthy postmenopausal women.

The effects of caffeine consumption on rates of change in bone mineral density (BMD) were examined in 205 healthy, nonsmoking, postmenopausal women. BMD of the spine and total body were measured by dual-energy x-ray absorptiometry, and dietary intakes by food-frequency questionnaire. Among women with calcium intakes above the median (744 mg/d), 1-y rates of bone change--adjusted for years since menopause, body mass index, physical activity, and baseline BMD--did not differ by caffeine intake. However, among women consuming less calcium, those with the highest caffeine intakes (> 450 mg/d) had significantly more bone loss (ANCOVA, P < 0.05) than did women consuming less caffeine (0-171 and 182-419 mg/d). Percent change in BMD by lowest to highest tertile of caffeine consumption was 0.26 +/- 2.74, 0.70 +/- 2.70, and -1.36 +/- 2.70 at the spine and -0.19 +/- 1.24, 0.23 +/- 1.23, and -0.68 +/- 1.25 at the total body. Daily consumption of caffeine in amounts equal to or greater than that obtained from about two to three servings of brewed coffee may accelerate bone loss from the spine and total body in women with calcium intakes below the recommended dietary allowance of 800 mg.

Coordinated strategies for controlling micronutrient malnutrition: a technical workshop.

Participants in a November 1991 workshop concluded that coordinated strategies for controlling malnutrition due to iodine, iron, vitamin A and other micronutrients deficiencies are technically feasible and should be given consideration in planning control efforts. Coordinated surveys involving clinical, biochemical and dietary assessment of multiple micronutrients are feasible. Multiple fortification is also possible using such vehicles as salt, processed rice or sugar. Supplementation efforts can be integrated with existing health care programs. Food-based strategies are also effective. The best examples have been community-based and have included a strong nutrition and health education component designed to change food consumption patterns, improve food preservation and preparation practices, and link income-generating activities with food production activities. Successful coordinated efforts will require a strong political commitment and a supportive infrastructure. Specific recommendations include the formation of national coordinating bodies for micronutrient deficiency control, establishment of a micronutrient information network and expansion of technical exchange and training.

Effect of aluminium on mineralization of rat third molar in vitro.

Crl: COBS rat third-molar explants were cultured for 12 days in either 0.6 X 10(-2), 4 X 10(-2) or 6 X 10(-2) mM aluminium, or for 12 days with exposure to 13 X 10(-2) mM Al at different 6-day intervals. Total protein, alkaline phosphatase, calcium and phosphorous were measured to evaluate cell viability and the degree of mineralization. Al in concentrations above 4 X 10(-2) mM significantly reduced the Ca and P content of explants cultured for 12 days. Explants exposed to 13 X 10(-2) mM Al for the first 6 days had less Ca and P than those exposed for the last 6 days of culture. Haematoxylin and eosin-stained sections of explants showed no gross abnormalities.

In vivo and in vitro study of the effects of vitamin A deficiency on rat third molar development.

We have examined the effect of in vivo vitamin A status on subsequent rat third molar formation and mineralization in an in vitro organ culture system. Vitamin A deficiency imposed during an eight-day in vitro period caused effects very similar to those of vitamin A deficiency imposed on rats in vivo. Analysis of the data also demonstrates that retinoic acid is capable of reversing the interference in mineralization of third molars induced by vitamin A deficiency in the organ culture system.

Effects of vitamin A deficiency on rat incisor formation.

Vitamin A deficiency (A-) is known to cause morphologic changes in tooth structures. However, its effects on glycosaminoglycan (GAG) distribution in dental pulp, and the role of retinoic acid (RA) in altering these effects are not clearly defined. Tissue changes induced by vitamin A deficiency and RA administration were evaluated histologically in incisors of rats fed on one of 3 different diets: a) vitamin A sufficient (A+); b) vitamin A deficient (A-); and c) vitamin A deficient supplemented with retinoic acid (A-/RA). Four weeks after the onset of vitamin A deficiency, all rats were killed and their 4 continuously erupting incisors evaluated histologically. A- rats had altered dentine and pulp with disrupted histodifferentiation of pulpal mesenchymal cells to normal odontoblasts. The frequency of these abnormalities in dentine and pulp was lower in A-/RA rats. The enamel organ was unremarkable in the 4-week deficient period. Using special stains, we noted that pulpal GAG accumulation in A- and A-/RA rats was limited to the lingual area, while in A+ rats, GAG were distributed throughout. These data suggest that vitamin A deficiency affects histodifferentiation of pulpal mesenchymal cells to odontoblasts, as well as GAG distribution in pulp. RA administration reduces the A- changes and therefore, appears to have some activity in dentinogenesis.

Organ culture study of effect of vitamin-A-deficiency on rat third molar development.

A culture procedure for rat third molars suitable for nutritional-developmental studies is described. Unerupted third molars from 12-day-old rats were cultured in BGJb media containing 20 per cent rat serum and supplemented with 25 mM HEPES buffer, 25 mg ascorbic acid, 20 mg L-glutamine, 12 mg penicillin G and 10 mg streptomycin sulphate per 100 ml of media. Molars were cultured at the liquid-gas interphase using a 50 per cent O2, 45 per cent N2, 5 per cent CO2 gas mixture at 10 lb-psig (pounds per square inch guage). Molar cultures were maintained successfully for 9-14 days without evidence of necrosis, although they developed at a slower rate than in vivo. Molars cultured in 50 per cent O2 compared to those cultured in 21 per cent O2 for periods of 2, 4, 6 and 8 days had higher values for protein, alkaline phosphatase (AP), Ca, P and Ca/P. Vitamin-A-deficiency gave lower values for AP, Ca, P, Ca/P, 45Ca, 35S and [14C]-proline uptake. Histologically, A - molars had atrophic ameloblasts, some foci of squamous metaplasia and abnormal keratin formation. Thus, deficiency of vitamin A imposed during in-vitro development of rat third molars retarded dentinogenesis and interfered with early mineralization of enamel and dentine.

Interaction of vitamin A deficiency and excess fluoride in calcification of rat bones and teeth.

Using a 2 X 2 factorial design, we evaluated the possible interaction of vitamin A deficiency and excess fluoride in rat dentin and bone. Simultaneous presence of excess fluoride plus vitamin A deficiency resulted in a significant decrease in bone fluoride concentration compared to the presence of excess fluoride alone. Vitamin A deficiency alone significantly reduced calcium concentration in dentin formed during the deficient period.