Supplemental vitamin D increases serum cytokines in those with initially low 25-hydroxyvitamin D: a randomized, double blind, placebo-controlled study.

The purpose of this study was to determine if vitamin D status before supplementation influences the cytokine response after supplemental vitamin D. Forty-six reportedly healthy adults (mean(SD); age, 32(7) y; body mass index (BMI), 25.3(4.5) kg/m(2); serum 25-hydroxyvitamin D (25(OH)D), 34.8(12.2) ng/mL) were randomly assigned (double blind) to one of three groups: (1) placebo (n=15), or supplemental vitamin D (cholecalciferol) at (2) 4000 (n=14) or (3) 8000IU (n=17). Supplements were taken daily for 35days. Fasting blood samples were obtained before (Baseline, Bsl) and 35-days after (35-d) supplementation. Serum 25(OH)D, 1,25-dihydroxyvitamin D (1,25(OH)D), cytokines, and intact parathyroid hormone with calcium were measured in each blood sample. Supplemental vitamin D increased serum 25(OH)D (4000IU, ≈29%; 8000IU, ≈57%) and 1,25(OH)D (4000IU, ≈12%; 8000IU, ≈38%) without altering intact parathyroid hormone or calcium. The vitamin D metabolite increases in the supplemental vitamin D groups (n=31) were dependent on initial levels as serum 25(OH)D (r=-0.63, p<0.05) and 1,25(OH)D (r=-0.45, p<0.05) at Bsl correlated with their increases after supplementation. Supplemental vitamin D increased interferon (IFN)-γ and interleukin (IL)-10 in subjects that were vitamin D insufficient (serum 25(OH)D<29ng/mL) compared to sufficient (serum 25(OH)D⩾30ng/mL) at Bsl. We conclude that supplemental vitamin D increase a pro- and anti-inflammatory cytokine in those with initially low serum 25(OH)D.

Vitamin D sufficiency associates with an increase in anti-inflammatory cytokines after intense exercise in humans.

The purpose of this study was to identify the influence of vitamin D status (insufficient vs. sufficient) on circulating cytokines and skeletal muscle strength after muscular injury. To induce muscular injury, one randomly selected leg (SSC) performed exercise consisting of repetitive eccentric-concentric contractions. The other leg served as the control. An averaged serum 25(OH)D concentration from two blood samples collected before exercise and on separate occasions was used to establish vitamin D insufficiency (<30ng/mL, n=6) and sufficiency (>30ng/mL, n=7) in young, adult males. Serum cytokine concentrations, single-leg peak isometric force, and single-leg peak power output were measured before and during the days following the exercise protocol. The serum IL-10 and IL-13 responses to muscular injury were significantly (both p<0.05) increased in the vitamin D sufficient group. The immediate and persistent (days) peak isometric force (p<0.05) and peak power output (p<0.05) deficits in the SSC leg after the exercise protocol were not ameliorated with vitamin D sufficiency. We conclude that vitamin D sufficiency increases the anti-inflammatory cytokine response to muscular injury.

Circulating pro-inflammatory cytokines are elevated and peak power output correlates with 25-hydroxyvitamin D in vitamin D insufficient adults.

The purpose of this study was to identify circulating cytokines, skeletal muscle strength, and peak power output in young adults with contrasting serum 25-hydroxyvitamin D (25(OH)D) concentrations. Serum 25(OH)D, inflammatory cytokines, muscle strength, and peak power output were, therefore, measured in young adults (25-42 years). Data were collected during the winter to avoid the seasonal influence on serum 25(OH)D. After serum 25(OH)D concentration measurements, subjects were separated into one of two groups: (1) vitamin D insufficient [serum 25(OH)D ≤32 ng/mL, n = 14], or (2) vitamin D sufficient [serum 25(OH)D >32 ng/mL, n = 14]. Following group allocation, serum 25(OH)D concentrations were significantly (p < 0.05) lower and pro-inflammatory cytokines [interleukin (IL)-2, IL-1ß, tumor necrosis factor-α, and interferon-γ] were significantly (all p < 0.05) greater in vitamin D insufficient adults. An anti-inflammatory cytokine (i.e., IL-10; p > 0.05), peak isometric forces (p > 0.05), and peak power outputs (p > 0.05) were not significantly different between vitamin D groups. However, peak power outputs correlated with serum 25(OH)D concentrations in vitamin D insufficient (r = 0.55, p < 0.05) but not in vitamin D sufficient adults (r = -0.27, p = 0.36). Based on these data, we conclude that vitamin D insufficiency, in part, could result in pro-inflammatory stress without altering muscular strength or function in young adults. Future research investigating the causality of the correlation between low-serum 25(OH)D and peak power output in young adults is required.

Supplemental vitamin D enhances the recovery in peak isometric force shortly after intense exercise.

BACKGROUND: Serum 25-hydroxyvitamin D (25(OH)D) concentrations associate with skeletal muscle weakness (i.e., deficit in skeletal muscle strength) after muscular injury or damage. Although supplemental vitamin D increases serum 25(OH)D concentrations, it is unknown if supplemental vitamin D enhances strength recovery after a damaging event. METHODS: Reportedly healthy and modestly active (30 minute of continuous physical activity at least 3 time/week) adult males were randomly assigned to a placebo (n = 13, age, 31(5) y; BMI, 26.9(4.2) kg/m2; serum 25(OH)D, 31.0(8.2) ng/mL) or vitamin D (cholecalciferol, 4000 IU; n = 15; age, 30(6) y; BMI, 27.6(6.0) kg/m2; serum 25(OH)D, 30.5(9.4) ng/mL) supplement. Supplements were taken daily for 35-d. After 28-d of supplementation, one randomly selected leg performed an exercise protocol (10 sets of 10 repetitive eccentric-concentric jumps on a custom horizontal plyo-press at 75% of body mass with a 20 second rest between sets) intended to induce muscle damage. During the exercise protocol, subjects were allowed to perform presses if they were unable to complete two successive jumps. Circulating chemistries (25(OH)D and alanine (ALT) and aspartate (AST) aminotransferases), single-leg peak isometric force, and muscle soreness were measured before supplementation. Circulating chemistries, single-leg peak isometric force, and muscle soreness were also measured before (immediately) and after (immediately, 1-h [blood draw only], 24-h, 48-h, 72-h, and 168-h) the damaging event. RESULTS: Supplemental vitamin D increased serum 25(OH)D concentrations (P < 0.05; ≈70%) and enhanced the recovery in peak isometric force after the damaging event (P < 0.05; ≈8% at 24-h). Supplemental vitamin D attenuated (P < 0.05) the immediate and delayed (48-h, 72-h, or 168-h) increase in circulating biomarkers representative of muscle damage (ALT or AST) without ameliorating muscle soreness (P > 0.05). CONCLUSIONS: We conclude that supplemental vitamin D may serve as an attractive complementary approach to enhance the recovery of skeletal muscle strength following intense exercise in reportedly active adults with a sufficient vitamin D status prior to supplementation.

Higher serum 25-hydroxyvitamin D concentrations associate with a faster recovery of skeletal muscle strength after muscular injury.

The primary purpose of this study was to identify if serum 25-hydroxyvitamin D (25(OH)D) concentrations predict muscular weakness after intense exercise. We hypothesized that pre-exercise serum 25(OH)D concentrations inversely predict exercise-induced muscular weakness. Fourteen recreationally active adults participated in this study. Each subject had one leg randomly assigned as a control. The other leg performed an intense exercise protocol. Single-leg peak isometric force and blood 25(OH)D, aspartate and alanine aminotransferases, albumin, interferon (IFN)-γ, and interleukin-4 were measured prior to and following intense exercise. Following exercise, serum 25(OH)D concentrations increased (p < 0.05) immediately, but within minutes, subsequently decreased (p < 0.05). Circulating albumin increases predicted (p < 0.005) serum 25(OH)D increases, while IFN-γ increases predicted (p < 0.001) serum 25(OH)D decreases. Muscular weakness persisted within the exercise leg (p < 0.05) and compared to the control leg (p < 0.05) after the exercise protocol. Serum 25(OH)D concentrations inversely predicted (p < 0.05) muscular weakness (i.e., control leg vs. exercise leg peak isometric force) immediately and days (i.e., 48-h and 72-h) after exercise, suggesting the attenuation of exercise-induced muscular weakness with increasing serum 25(OH)D prior to exercise. Based on these data, we conclude that pre-exercise serum 25(OH)D concentrations could influence the recovery of skeletal muscle strength after an acute bout of intense exercise.

Different doses of supplemental vitamin D maintain interleukin-5 without altering skeletal muscle strength: a randomized, double-blind, placebo-controlled study in vitamin D sufficient adults.

BACKGROUND: Supplemental vitamin D modulates inflammatory cytokines and skeletal muscle function, but results are inconsistent. It is unknown if these inconsistencies are dependent on the supplemental dose of vitamin D. Therefore, the purpose of this study was to identify the influence of different doses of supplemental vitamin D on inflammatory cytokines and muscular strength in young adults. METHODS: Men (n = 15) and women (n = 15) received a daily placebo or vitamin D supplement (200 or 4000 IU) for 28-d during the winter. Serum 25-hydroxyvitamin D (25(OH)D), cytokine concentrations and muscular (leg) strength measurements were performed prior to and during supplementation. Statistical significance of data were assessed with a two-way (time, treatment) analysis of variance (ANOVA) with repeated measures, followed by a Tukey's Honestly Significant Difference to test multiple pairwise comparisons. RESULTS: Upon enrollment, 63% of the subjects were vitamin D sufficient (serum 25(OH)D ≥ 30 ng/ml). Serum 25(OH)D and interleukin (IL)-5 decreased (P < 0.05) across time in the placebo group. Supplemental vitamin D at 200 IU maintained serum 25(OH)D concentrations and increased IL-5 (P < 0.05). Supplemental vitamin D at 4000 IU increased (P < 0.05) serum 25(OH)D without altering IL-5 concentrations. Although serum 25(OH)D concentrations correlated (P < 0.05) with muscle strength, muscle strength was not changed by supplemental vitamin D. CONCLUSION: In young adults who were vitamin D sufficient prior to supplementation, we conclude that a low-daily dose of supplemental vitamin D prevents serum 25(OH)D and IL-5 concentration decreases, and that muscular strength does not parallel the 25(OH)D increase induced by a high-daily dose of supplemental vitamin D. Considering that IL-5 protects against viruses and bacterial infections, these findings could have a broad physiological importance regarding the ability of vitamin D sufficiency to mediate the immune systems protection against infection.