Vitamin D Supplementation, Glycemic Control, and Insulin Resistance in Prediabetics: A Meta-Analysis.

Diabetes prevention is a public health priority. Vitamin D supplementation may help prevent the development of diabetes in persons at increased risk. We performed a meta-analysis of controlled clinical trials that assessed glycemic outcome measures among adults at risk for type 2 diabetes, including prediabetes, overweight, or obesity. We searched PUBMED/ MEDLINE, CINAHL, and Google Scholar databases for trials published prior to April 2017. Placebo-controlled clinical trials with random allocation to vitamin D with or without calcium supplementation were selected. Data collection included country, study design, inclusion criteria, sample size, form, and dose of vitamin D, supplementation interval, control group, duration, participant characteristics, comorbidities, baseline and follow-up serum 25-hydroxyvitamin D [25(OH)D] concentration, and available outcome measures [glycosylated hemoglobin (HbA1c), fasting plasma glucose, plasma glucose after 2-hour oral glucose tolerance test, and homeostatic model assessment of insulin resistance (HOMA-IR)]. Data synthesis was conducted using random-effect models (PROSPERO registration no. CRD42017055326). Twenty-eight trials, representing 3848 participants, met the eligibility criteria. Compared with the control group, vitamin D supplementation significantly reduced HbA1c level by -0.48% (95% CI, -0.79 to -0.18), fasting plasma glucose level by -0.46 mmol/L (95% CI, -0.74 to -0.19), and HOMA-IR level by -0.39 (95% CI, -0.68 to -0.11). Subgroup analysis revealed that the effects of vitamin D supplementation on different glycemic measures were influenced by age, calcium coadministration, vitamin D deficiency, serum 25(OH)D level after supplementation, and duration of supplementation. Vitamin D supplementation and improved vitamin D status improved glycemic measures and insulin sensitivity and may be useful as part of a preventive strategy for type 2 diabetes.

The Association between Serum 25(OH)D Status and Blood Pressure in Participants of a Community-Based Program Taking Vitamin D Supplements.

BACKGROUND: Vitamin D deficiency is a risk factor for hypertension. METHODS: We assessed 8155 participants in a community-based program to investigate the association between serum 25-hydroxyvitamin D (25(OH)D) status and blood pressure (BP) and the influence of vitamin D supplementation on hypertension. Participants were provided vitamin D supplements to reach a target serum 25(OH)D > 100 nmol/L. A nested case-control study was conducted to examine the effect of achieving physiological vitamin D status in those who were hypertensive and not taking BP-lowering medication, and hypertensive participants that initiated BP-lowering medication after program entry. RESULTS: At baseline, 592 participants (7.3%) were hypertensive; of those, 71% were no longer hypertensive at follow-up (12 ± 3 months later). There was a significant negative association between BP and serum 25(OH)D level (systolic BP: coefficient = -0.07, p < 0.001; diastolic BP: coefficient = -0.1, p < 0.001). Reduced mean systolic (-18 vs. -14 mmHg) and diastolic (-12 vs. -12 mmHg) BP, pulse pressure (-5 vs. -1 mmHg) and mean arterial pressure (-14 vs. -13 mmHg) were not significantly different between hypertensive participants who did and did not take BP-lowering medication. CONCLUSION: Improved serum 25(OH)D concentrations in hypertensive individuals who were vitamin D insufficient were associated with improved control of systolic and diastolic BP.

The Effect of Improved Serum 25-Hydroxyvitamin D Status on Glycemic Control in Diabetic Patients: A Meta-Analysis.

Background: Type 2 diabetes is a global health concern, with an increased prevalence and high cost of treatment. Objective: The aim of this systematic review and meta-analysis was to determine the effect of vitamin D supplementation and improved vitamin D status on glycemia and insulin resistance in type 2 diabetic patients. Data Source: We searched PUBMED/Medline, Cumulative Index to Nursing and Allied Health, and Cochrane Library (until January 2017). Study Selection: Prospective clinical trials were selected evaluating the impact of vitamin D supplementation on glycosylated hemoglobin (HbA1c), serum fasting plasma glucose (FPG), and homeostatic model assessment of insulin resistance (HOMA-IR) in diabetic patients. Data Extraction and Synthesis: We used a random-effects model to synthesize quantitative data, followed by a leave-one-out method for sensitivity analysis. The systematic review registration was CRD42017059555. From a total of 844 entries identified via literature search, 24 controlled trials (1528 individuals diagnosed with type 2 diabetes) were included. The meta-analysis indicated a significant reduction in HbA1c [mean difference: -0.30%; 95% confidence interval (CI): -0.45 to -0.15, P < 0.001], FPG [mean difference: -4.9 mg/dL (-0.27 mmol/L); 95% CI: -8.1 to -1.6 (-0.45 to -0.09 mmol/L), P = 0.003], and HOMA-IR (mean difference: -0.66; 95% CI: -1.06 to -0.26, P = 0.001) following vitamin D supplementation and significant increase in serum 25-hydroxyvitamin D levels [overall increase of 17 ± 2.4 ng/mL (42 ± 6 nmol/L)]. Conclusions: Vitamin D supplementation, a minimum dose of 100 µg/d (4000 IU/d), may significantly reduce serum FPG, HbA1c, and HOMA-IR index, and helps to control glycemic response and improve insulin sensitivity in type 2 diabetic patients.

Vitamin D status is associated with disease activity among rheumatology outpatients.

UNLABELLED: The co-existence of high prevalence of vitamin D inadequacy among Canadians and high prevalence of systematic autoimmune rheumatic diseases (SARDs) raise the question on relationship between the two situations. OBJECTIVE: To determine vitamin D status in known cases of common SARDs and compare to those with non-autoimmune diseases; further, to evaluate the impact of vitamin D on disease activity in rheumatoid arthritis (RA) cases. METHODS: In a retrospective case-control study design, we evaluated 116 patients in a community clinic classified in two groups, CONTROL GROUP: patients with non-rheumatic disease (n = 56), and Case group: those with rheumatic diseases (n = 60). We compared plasma vitamin D status (25(OH)D), indicators of disease activity and other potential confounders. Further, we determined factors associated with disease activity in RA cases. RESULTS: The plasma 25(OH)D was significantly lower in Case group (64.8 ± 29.8) compared to CONTROL GROUP (86.8 ± 37.7). High number of SARDs outpatients 56%) had considerably low plasma 25(OH)D concentration. RA cases with low plasma 25(OH)D had over five times higher risk of disease activity (OR = 5.15 95% CI 1.16, 22.9; p = 0.031). CONCLUSION: Inadequate vitamin D status in SARDs cases, along with considerably strong association with disease activity in RA cases, indicate the need for proper evaluation of vitamin D status in this clinical population. Moreover, appropriate training should be given to the patients to ensure the intake of the recommended amount of vitamin D per day through diet or supplement.

Vitamin D insufficiency and bone mineral status in a population of newcomer children in Canada.

BACKGROUND: Low levels of circulating vitamin D are more likely to be found in those with darker skin pigmentation, who live in areas of high latitude, and who wear more clothing. We examined the prevalence of vitamin D deficiency and inadequacy in newcomer immigrant and refugee children. METHODS: We evaluated circulating vitamin D status of immigrant children at the national level. Subsequently, we investigated vitamin D intake, circulating vitamin D status, and total body bone mineral content (TBBMC) in newcomer children living in Saskatchewan. RESULTS: In the sample of newcomer children in Saskatchewan, the prevalence of inadequacy in calcium and vitamin D intakes was 76% and 89.4%, respectively. Vitamin D intake from food/supplement was significantly higher in immigrants compared to refugees, which accords with the significant difference in serum status. Circulating vitamin D status indicated that 29% of participants were deficient and another 44% had inadequate levels of serum 25(OH)D for bone health. Dietary vitamin D intake, sex, region of origin, and length of stay in Canada were significant predictors of serum vitamin D status. RESULTS for TBBMC revealed that 38.6% were found to have low TBBMC compared to estimated values for age, sex, and ethnicity. In the regression model, after controlling for possible confounders, children who were taller and had greater circulating vitamin D also had greater TBBMC. Nationally, immigrant children, particularly girls, have significantly lower plasma 25(OH)D than non-immigrant children. INTERPRETATION: Newcomer immigrant and refugee children are at a high risk of vitamin D deficiency and inadequacy, which may have serious negative consequences for their health.

Effect of exercise training combined with isoflavone supplementation on bone and lipids in postmenopausal women: a randomized clinical trial.

We determined the effects of 2 years of exercise training and soy isoflavone supplementation on bone mass and lipids in postmenopausal women provided with calcium and vitamin D. Women were randomized to four groups: exercise training (Ex); isoflavone supplementation (Iso: 165 mg/d [105 mg/d aglycone equivalent]); combined Ex and Iso (ExIso); and placebo (control). Exercise included resistance training (2 days/week) and walking (4 days/week). Our primary outcomes were lumbar spine and hip bone mineral density (BMD). Secondary outcomes included hip geometry, tibia and radius speed of sound (SOS), dynamic balance (6 m backward tandem walking), blood lipids, mammography, and endometrial thickness. A total of 351 women (Ex = 86, Iso = 90, ExIso = 87, control = 88) were randomized, with 298 analyzed at 2 years (Ex = 77, Iso = 76, ExIso = 72, control = 73). There was a significant interaction for total hip BMD (p < 0.001) such that ExIso had a greater rate of decrease (absolute change [95% confidence interval] = -0.018 [-0.024, -0.012] g/cm(2) ) than either the Ex or Iso groups alone (-0.005 [-0.01, 0.001] and -0.005 [-0.011, 0.001] g/cm(2) , respectively). There were no differences between groups for changes in lumbar spine BMD and minimal significant changes in hip geometric properties and bone SOS. Exercise groups improved dynamic balance as measured by a decrease in backward tandem walking time over 6 m (p = 0.017). Isoflavone groups decreased low density lipoproteins (Iso: -0.20 [-0.37, -0.02] mmol/L; ExIso: -0.23 [-0.40, -0.06] mmol/L; p = 0.003) compared to non-isoflavone groups (Ex: 0.01 [-0.16, 0.18] mmol/L; control: -0.09 [-0.27, 0.08] mmol/L) and had lower adverse reports of menopausal symptoms (14% versus 33%; p = 0.01) compared to non-isoflavone groups. Isoflavone supplementation did not increase endometrial thickness or abnormal mammograms. We conclude exercise training and isoflavone supplementation maintain hip BMD compared to control, but these two interventions interfere with each other when combined. Isoflavone supplementation decreased LDL and adverse events related to menopausal symptoms.

The vitamin D status of Canadians relative to the 2011 Dietary Reference Intakes: an examination in children and adults with and without supplement use.

BACKGROUND: The 2011 Dietary Reference Intakes (DRIs) for vitamin D use 25-hydroxyvitamin D [25(OH)D] concentrations to define vitamin D deficiency (<30 nmol/L), the Estimated Average Requirement (40 nmol/L), and the Recommended Dietary Allowance (RDA; 50 nmol/L). The Canadian population has not yet been assessed according to these recommendations. OBJECTIVE: We determined the prevalence of meeting DRI recommendations and the role of vitamin D supplement use among Canadians aged 6-79 y. DESIGN: Plasma 25(OH)D from a representative sample of Canadians in the Canadian Health Measures Survey-Cycle 1 (n = 5306) were used. Supplement use was assessed by household interview. Concentrations of 25(OH)D were compared in supplement users and nonusers by season and race. RESULTS: Overall, 5.4%, 12.7%, and 25.7% of the participants had 25(OH)D concentrations below the 30-, 40-, and 50-nmol/L cutoffs, respectively. In white Canadians, plasma 25(OH)D concentrations ranged from an undetectable percentage with concentrations <30 nmol/L in summer to 24.5% with concentrations <50 nmol/L in winter; the corresponding values ranged from 12.5% to 53.1% in nonwhite Canadians. Supplement users had significantly higher 25(OH)D concentrations than did nonusers, and no seasonal differences were found. In nonsupplement users, the prevalence of 25(OH)D concentrations <50 nmol/L in winter was 37.2% overall and was 60.7% in nonwhites. CONCLUSIONS: One-quarter of Canadians did not meet the RDA, but the use of vitamin D supplements contributed to a better 25(OH)D status. Nonwhite Canadians had the highest risk of not achieving DRI recommendations. More than one-third of Canadians not using supplements did not meet the RDA in winter. This suggests that current food choices alone are insufficient to maintain 25(OH)D concentrations of 50 nmol/L in many Canadians, especially in winter.

Barriers to healthful eating and supplement use in lower-income adults.

PURPOSE: We investigated barriers to healthful eating and vitamin/mineral supplement use among groups at risk for low nutrient intakes, particularly those with low income. METHODS: Twelve focus groups (73 participants) and 11 key informant interviews were conducted in Saskatoon, Saskatchewan. Focus group participants represented a diverse population. Key informants included health professionals and personnel from community-based organizations who worked in a low-income area. Focus group meetings and key informant interviews were audiotaped and transcribed; thematic coding was used to identify key concepts. RESULTS: The focus groups and interviews revealed five themes on barriers to healthful eating and to the use of vitamin/mineral supplements: knowledge, income, accessibility, health, and preferences. Key informants were aware of the barriers, and were able to see not only individual and family reasons but also societal influences. CONCLUSIONS: The study results provide valuable information for focusing efforts on reducing barriers to healthful eating and to appropriate vitamin/mineral supplement use.

Despite mandatory fortification of staple foods, vitamin D intakes of Canadian children and adults are inadequate.

Vitamin D is largely obtained through sun-induced skin synthesis and less from dietary sources, but during Canadian winters, skin synthesis is non-existent. The objective of this study was to estimate vitamin D intakes in Canadians from food sources. Data used in this study included food intakes of Canadians reported in the 2004 Canadian Community Health Survey Cycle 2.2 (CCHS 2.2), a nationally representative sample of 34,789 persons over the age of 1 year. The mean+/-SD dietary intake of vitamin D from food of Canadians was 5.8+/-0.1 microg/day, with males 9-18 years having the highest mean intakes (7.5+/-0.2 microg/day) and females 51-70 years having the lowest intakes (5.2+/-0.3 microg/day). Males in all age groups had higher intakes than females and White Canadians had higher vitamin D intakes than Non-Whites in most age sex groups. Milk products contributed 49% of dietary vitamin D followed by meat and meat-alternatives (31.1%). The majority of Canadians consume less than current recommended intake of vitamin D from food. Consideration should be given to strategies to improve vitamin D intake of Canadians by increasing both the amount of vitamin D added to foods and range of foods eligible for fortification.

Socio-economic status and vitamin/ mineral supplement use in Canada.

BACKGROUND: The link between diet quality and socio-economic status (SES) may extend to the use of vitamin/ mineral supplements. This article examines factors related to Canadians' use of such supplements, with emphasis on associations with household income and education. DATA AND METHODS: The data are from the 2004 Canadian Community Health Survey-Nutrition (n = 35,107). The prevalence of vitamin/mineral supplement consumption during the previous month was recorded. Supplement use at the national level was estimated by age/sex groups, SES and chronic conditions. Logistic regression was used to determine significant associations between socio-economic factors and vitamin/mineral supplement use. Estimates of usual calcium intake from food and from food plus supplements were obtained using SIDE-IML. RESULTS: The prevalence of supplement use was significantly higher in females than in males in all age groups 14 or older. Age, being female, high household income and education, and being food-secure were positively associated with supplement use. Supplement use substantially increased the percentage of the population, particularly older adults, meeting the Adequate Intake level for calcium. INTERPRETATION: The reported use of vitamin/mineral supplements varies by age, sex and SES. The relatively low prevalence of use among Canadians of low SES is similar to findings from American studies. These individuals, already at risk for inadequate intake from food, do not make up the difference with vitamin/ mineral supplements.

A randomized controlled trial of the effects of flaxseed lignan complex on metabolic syndrome composite score and bone mineral in older adults.

A randomized double-blind placebo controlled study design was used to assess the effects of flaxseed lignan complex supplementation during exercise training on a metabolic syndrome composite score and osteoporosis risk in older adults. A total of 100 subjects (>or=50 years) were randomized to receive flaxseed lignan (543 mg.day-1 in a 4050 mg complex) or placebo while completing a 6 month walking program (30-60 min.day-1, 5-6 days.week-1). Fasting serum glucose, triacylglycerol (TAG), high-density lipoprotein (HDL) cholesterol, low-density lipoprotein cholesterol, total cholesterol, interleukin-6, and tumor necrosis factor-alpha were measured every 2 months, while body composition, bone mineral density, and resting blood pressure were assessed at baseline and at 6 months. A composite Z score of 6 risk factors for metabolic syndrome (fasting glucose, HDL cholesterol, TAG, abdominal adiposity, blood pressure, and inflammatory cytokines) was calculated at baseline and at 6 months. Men taking placebo increased metabolic syndrome composite Z score (p < 0.05), but there were no changes in the other groups. A significant group x sex x time interaction was noted for TAG (p = 0.017) and diastolic blood pressure (p = 0.046), with men taking flaxseed lignan decreasing diastolic blood pressure relative to men taking placebo, and men taking placebo increasing TAG relative to men taking flax lignan. There were no differences between groups for change in bone measures, body composition, lipoproteins, or cytokines. Males taking the flaxseed lignan complex reduced metabolic syndrome score relative to men taking placebo, but a similar trend was not seen in females. Flaxseed lignan had no effect on bone mineral density or content, body composition, lipoproteins, glucose, or inflammation.

Many adult Canadians are not meeting current calcium recommendations from food and supplement intake.

The objective of this study was to determine trends in calcium intake from foods of Canadian adults from 1970-1972 to 2004. We compiled the calcium intake of adults (aged >or=19 years) from foods from Nutrition Canada (1970-1972; n = 7036); 9 provincial nutrition surveys (1990-1999; n = 16 915); and the 2004 Canadian Community Health Survey 2.2 (n = 20 197). Where possible, we used published confidence intervals to test for significant differences in calcium intake. In 2004, the mean calcium intake of Canadians was below Dietary Reference Intake recommendations for most adults, with the greatest difference in older adults (>or=51 years), in part because the recommended calcium intake for this group is higher (1200 mg) than that for younger adults (1,000 mg). The calcium intake of males in every age category was greater than that of females. Calcium intake increased from 1970 to 2004, yet, despite the introduction of calcium-fortified beverages to the market in the late 1990s, increases in calcium intake between 1970 and 2004 were modest. Calcium intakes in provinces were mostly similar in the 1990s and in 2004, except for women in Newfoundland and Labrador, who consumed less, especially in the 1990s, and for young men in 2004 in Prince Edward Island, who consumed more. When supplemental calcium intake was added, mean intakes remained below recommended levels, except for males 19-30 years, but the prevalence of adequacy increased in all age groups, notably for women over 50 years. The calcium intake of Canadian adults remains in need of improvement, despite fortification and supplement use.

Is calcium supplementation a risk factor for cardiovascular diseases in older women?

Low intake of dietary calcium is related to bone loss and fragility fracture in older adults, especially postmenopausal women. Contradictory findings have been reported from studies that investigated the association between calcium supplementation and hypertension and the risk of stroke and cardiovascular disease. Misinterpretation of findings from studies that are not primarily designed to address these issues might overshadow the benefits of dietary calcium. Until well-designed studies address the current uncertainties, the possible detrimental effect (e.g., hypercalcemia and its complications) of higher-than-recommended calcium intake should be balanced against the likely benefits of calcium on bone, particularly in elderly women.

Does the effect of soy phytoestrogens on bone in postmenopausal women depend on the equol-producing phenotype?

Plant-derived phytoestrogens are considered to be an alternative therapy for the prevention and control of bone loss in postmenopausal women. However, there are contradictory findings among clinical studies in the efficacy of soy isoflavones on bone metabolism in postmenopausal women. Inter-individual differences in gut bacteria metabolism of isoflavones to produce equol (the equol-producing phenotype) might partly explain these discrepancies. Among several trials in this area of research, few studies took the equol-producing phenotype into consideration, and those studies support the importance of this phenotype in the effect of soy isoflavones on bone health among post-menopausal women. Greater consideration of the equol-producing phenotype in the design of studies investigating the effect of soy isoflavones on bone health of postmenopausal women may provide more useful information.

Calcium supplementation trials and bone mass development in children, adolescents, and young adults.

The development of bone mass during childhood through young adulthood is an important determinant of bone health later in life, and calcium is the major building block. Most randomized, double-blind, placebo-controlled trials of calcium supplementation have been done in girls; however, calcium supplementation in boys has been investigated in recent studies. Positive short-term effects on bone measures during growth has been shown in boys and girls, particularly in weight-bearing appendicular bone, although the lifelong effect is not certain.