Gene expression in breast and adipose tissue after 12 months of weight loss and vitamin D supplementation in postmenopausal women.

Adipose tissue is involved in the etiology of postmenopausal breast cancer, possibly through increased sex steroid hormone production, inflammation, and altered adipokines. Vitamin D may affect these pathways but its effect on gene expression in different tissues has not been examined. Within a double-blind, 12-month placebo-controlled randomized trial, we compared 2000 IU/day oral vitamin D3 supplementation (N = 39) vs. placebo (N = 40) on the expression of 5 genes in breast and adipose tissue in overweight/obese postmenopausal women (50-75 years). All participants had serum 25-hydroxyvitamin D (25(OH)D) levels ≥ 10-<32 ng/mL ("insufficient") and concurrently completed a behavioral weight loss program. Random periareolar fine needle aspiration (RPFNA) and abdominal subcutaneous adipose tissue biopsies were performed at baseline and 12 months. Changes in expression of aromatase (CYP19A1), peroxisome proliferator-activated receptor gamma (PPARG), adiponectin (ADIPOQ), monocyte-chemoattractant protein 1 (MCP-1), and vitamin D receptor (VDR) were analyzed by qRT-PCR. Compared to placebo, 2000 IU vitamin D did not show significant effects on gene expression in breast or adipose tissue. Replete women (i.e., 25(OH)D ≥ 32 ng/mL; N = 17) showed a small decrease in MCP-1 expression compared to an increase among women who remained 'insufficient' despite supplementation (N = 12) (Replete:-1.6% vs. Non-replete: 61.2%, p = 0.015) in breast, but not adipose tissue. No statistically significant differences in gene expression were detected according to degree of weight loss. Vitamin D repletion during weight loss may have different effects on gene expression in breast and adipose tissue. Further research on the localized effects of vitamin D is needed to determine its effect on breast cancer risk.

Repletion of vitamin D associated with deterioration of sleep quality among postmenopausal women.

Reduced health-related quality of life (HRQOL), depressive symptoms and poor sleep quality are important health issues among postmenopausal women and may be associated with low vitamin D status. Overweight postmenopausal women, with serum 25-hydroxyvitamin D [25(OH)D] 10-32ng/m, were recruited in Seattle, WA (2010-2012) and randomly assigned to 12months of weight loss +2000IU oral vitamin D3/day or weight loss+daily placebo. The weight-loss program included a reduced-calorie diet and 225min/week of moderate-to-vigorous aerobic activity. Eight subscales of HRQOL were assessed by the MOS 36-Item Short-Form Health Survey. Depressive symptoms were assessed using the Brief Symptom Inventory-18, and sleep quality was assessed using the Pittsburg Sleep Quality Index (PSQI). Mean 12-month changes in HRQOL, depressive symptoms and sleep quality were compared between groups (intent-to-treat) using generalized estimating equations. Compared to placebo, women receiving vitamin D did not experience any significant change in depressive symptoms (p=0.78), HRQOL subscales (all p>0.05), or overall sleep quality (p=0.21). However, a greater magnitude of change in serum 25(OH)D was associated with an increased need to take medications to sleep (ptrend=0.01) and overall worse sleep quality (ptrend<0.01). Women who became vitamin D replete (≥32ng/mL) also showed a deterioration in total PSQI sleep quality score compared to women who remained <32ng/mL despite supplementation, even after adjusting for relevant covariates (Non-Replete: -5.7% vs. Replete: +6.2%, p<0.01). Vitamin D supplementation of 2000IU/d may result in overall worse sleep quality for postmenopausal women with low circulating vitamin D undergoing weight loss.

Effects of Vitamin D3 Supplementation on Lean Mass, Muscle Strength, and Bone Mineral Density During Weight Loss: A Double-Blind Randomized Controlled Trial.

OBJECTIVES: To compare the effects of 12 months of vitamin D3 supplementation with that placebo on lean mass, bone mineral density (BMD), and muscle strength in overweight or obese postmenopausal women completing a structured weight-loss program. DESIGN: Double-blind, placebo-controlled randomized clinical trial. SETTING: Fred Hutchinson Cancer Research Center, Seattle, Washington. PARTICIPANTS: Postmenopausal women aged 50 to 75 with a body mass index (BMI) of 25 kg/m(2) or greater and a serum 25-hydroxyvitamin D (25(OH)D) concentration between 10.0 and 32.0 ng/mL (insufficient) (N = 218). INTERVENTION: Oral vitamin D3 2,000 IU/d or placebo in combination with a lifestyle-based weight loss intervention consisting of a reduction of 500 kcal to 1,000 kcal per day and 225 min/wk of moderate- to vigorous-intensity aerobic exercise. MEASUREMENTS: Serum 25(OH)D, body composition, and muscle strength were measured before randomization (baseline) and at 12 months. Mean changes of the groups were compared (intention to treat) using generalized estimating equations. RESULTS: Change in 25(OH)D was significantly different between the vitamin D and placebo groups at 12 months (13.6 ng/mL vs -1.3 ng/mL, P < .001), but no differences in change in lean mass (-0.8 kg vs -1.1 kg, P = .53) or BMD of the spine (-0.01 g/cm(2) vs 0.0 g/cm(2) , P = .82) or right femoral neck (both -0.01 g/cm(2) , P = .49) were detected between the groups. Leg strength decreased in the vitamin D group but not in the placebo group (-2.6 pounds vs 1.8 pounds, P = .03). In women randomized to vitamin D, achieving repletion (25(OH)D ≥ 32 ng/mL) did not alter results. CONCLUSION: Vitamin D3 supplementation during weight-loss decreased leg strength but did not alter changes in lean mass or BMD in postmenopausal women with vitamin D insufficiency.

Effects of vitamin D supplementation during weight loss on sex hormones in postmenopausal women.

OBJECTIVE: The aim of the study was to compare the effects of vitamin D3 supplementation versus placebo on serum sex hormones in postmenopausal women completing a 12-month diet + exercise weight loss program. METHODS: Two hundred eighteen overweight or obese women (50-75 y) with serum 25-hydroxyvitamin D at least 10 to less than 32 ng/mL ("insufficient") were randomized to either weight loss + 2,000 IU/day oral vitamin D3, or to weight loss + daily placebo. Serum sex hormone-binding globulin, estrone, total, free, and bioavailable estradiol, and testosterone were measured by radioimmunoassay before randomization and at 12 months. Mean changes were compared between groups (intent-to-treat) using generalized estimating equations. RESULTS: The 12-month changes in sex hormone-binding globulin, estrone, total, free, and bioavailable estradiol, and testosterone did not differ between groups (all P > 0.05). However, a greater increase in serum 25-hydroxyvitamin D was associated with a greater increase in sex hormone-binding globulin (Ptrend = 0.01), and larger decreases in free and bioavailable estradiol (Ptrend = 0.04, Ptrend = 0.03, respectively). In post-hoc analyses, we compared women randomized to vitamin D whose serum 25-hydroxyvitamin D remained insufficient (n = 38), to women who became replete (25-hydroxyvitamin D ≥32 ng/mL; n = 53). Replete women showed greater reductions in bioavailable estradiol (-1.8 vs -0.7 pg/mL), free testosterone (-0.8 vs -0.3 pg/mL), and bioavailable testosterone (-1.8 vs -0.6 ng/dL), and a greater increase in sex hormone-binding globulin (10.6 vs 4.7 nmol/L) (all P < 0.05), even after adjusting for differences in total 12-month weight loss. CONCLUSIONS: Overall, 12-month changes in sex hormone did not differ between groups. However, vitamin D repletion was associated with greater reductions in sex hormones during weight loss, with a possible dose-dependent effect. Future studies should test higher doses and target circulating 25-hydroxyvitamin D levels when measuring such effects.

Effect of Vitamin D3 Supplementation in Combination with Weight Loss on Inflammatory Biomarkers in Postmenopausal Women: A Randomized Controlled Trial.

Obesity and vitamin D deficiency are associated with risk for several cancers, possibly through inflammation and adipokine-related pathways. Two hundred and eighteen postmenopausal women with BMI > 25 kg/m(2) and low serum 25-hydroxyvitamin D (25(OH)D; ≥10-<32 ng/mL), were randomized to 12 months of either (i) weight-loss intervention + 2000 IU/day oral vitamin D3 or (ii) weight-loss intervention + daily placebo. Serum adiponectin, leptin, TNFα, IL6, IL1ß, IL8, and IL10, were measured by immunoassay, and a composite inflammatory biomarker score calculated. Using generalized estimating equations, mean changes in outcomes were compared between arms (intent-to-treat), adjusted for possible confounders. Analyses were also stratified by weight-loss (gained/no weight-loss; <5%; 5% to 10%; ≥10%). At 12 months, there were no significant differences in analyte changes between arms. In stratified analyses, participants randomized to vitamin D3 who lost 5% to 10% of baseline weight, versus participants who gained weight/had no weight-loss, had significantly greater decreases in levels of IL6 compared with those randomized to placebo: absolute change -0.75 pg/mL (-17.2%), placebo versus -1.77 pg/mL (-37.3%), vitamin D, P = 0.004. Similar but attenuated results were observed for participants who lost ≥10% of baseline weight: -0.41 pg/mL (-13.6%), placebo versus -0.67 pg/mL (-17.3%), vitamin D, P = 0.02. Effects of vitamin D3 supplementation on levels of IL1ß were inconsistent when stratified by weight loss. There were no intervention effects on IL10, TNFα, IL8, the composite score, adiponectin, or leptin, when stratified by weight-loss. In conclusion, vitamin D3 supplementation in combination with weight-loss of at least 5% of baseline weight was associated with significant reductions in levels of IL6.

Vitamin D3 supplementation during weight loss: a double-blind randomized controlled trial.

BACKGROUND: Vitamin D deficiency is associated with obesity; whether repletion supports weight loss and changes obesity-related biomarkers is unknown. OBJECTIVE: We compared 12 mo of vitamin D3 supplementation with placebo on weight, body composition, insulin, and C-reactive protein (CRP) in postmenopausal women in a weight-loss intervention. DESIGN: A total of 218 overweight/obese women (50-75 y of age) with serum 25-hydroxyvitamin D [25(OH)D] ≥10 ng/mL but <32 ng/mL were randomly assigned to weight loss + 2000 IU oral vitamin D3/d or weight loss + daily placebo. The weight-loss intervention included a reduced-calorie diet (10% weight loss goal) and 225 min/wk of moderate-to-vigorous aerobic activity. Mean 12-mo changes in weight, body composition, serum insulin, CRP, and 25(OH)D were compared between groups (intent-to-treat) by using generalized estimating equations. RESULTS: A total of 86% of participants completed the 12-mo measurements. The mean (95% CI) change in 25(OH)D was 13.6 (11.6, 15.4) ng/mL in the vitamin D3 arm compared with -1.3 (-2.6, -0.3) ng/mL in the placebo arm (P < 0.0001). Changes in weight [-7.1 (-8.7, -5.7) compared with -7.4 (-8.1, -5.4) kg], body mass index (in kg/m(2): both -2.8), waist circumference [-4.9 (-6.7, -2.9) compared with -4.5 (-5.6, -2.6) cm], percentage body fat [-4.1 (-4.9, -2.9) compared with -3.5 (-4.5, -2.5)], trunk fat [-4.1 (-4.7, -3.0) compared with -3.7 (-4.3, -2.9) kg], insulin [-2.5 (-3.4, -1.7) compared with -2.4 (-3.3, -1.4) µU/mL], and CRP [-0.9 (-1.2, -0.6) compared with -0.79 (-0.9, -0.4) mg/L] [corrected] were similar between groups (all P > 0.05). Compared with women who achieved 25(OH)D <32 ng/mL, women randomly assigned to vitamin D who became replete (ie, 25(OH)D ≥32 ng/mL) lost more weight [-8.8 (-11.1, -6.9) compared with -5.6 (-7.2, -5.0) kg; P = 0.05], waist circumference [-6.6 (-9.3, -4.3) compared with -2.5 (-4.6, -2.0) cm; P = 0.02], and percentage body fat [-4.7 (-6.1, -3.5) compared with -2.6 (-3.9, -2.2); P = 0.04]. Among women with complete pill counts (97% adherence), the mean decrease in CRP was 1.18 mg/mL (46%) in the vitamin D arm compared with 0.46 mg/mL (25%) in the placebo arm (P = 0.03). CONCLUSIONS: Vitamin D3 supplementation during weight loss did not increase weight loss or associated factors compared with placebo; however, women who became replete experienced greater improvements. This trial was registered at clinicaltrials.gov as NCT01240213.