Vitamin D supplementation protects against reductions in plasma 25-hydroxyvitamin D induced by open-heart surgery: Assess-d trial.

Low vitamin D (serum or plasma 25-hydroxyvitamin D (25(OH)D)) is a global pandemic and associates with a greater prevalence in all-cause and cardiovascular mortality and morbidity. Open-heart surgery is a form of acute stress that decreases circulating 25(OH)D concentrations and exacerbates the preponderance of low vitamin D in a patient population already characterized by low levels. Although supplemental vitamin D increases 25(OH)D, it is unknown if supplemental vitamin D can overcome the decreases in circulating 25(OH)D induced by open-heart surgery. We sought to identify if supplemental vitamin D protects against the acute decrease in plasma 25(OH)D propagated by open-heart surgery during perioperative care. Participants undergoing open-heart surgery were randomly assigned (double-blind) to one of two groups: (a) vitamin D (n = 75; cholecalciferol, 50,000 IU/dose) or (b) placebo (n = 75). Participants received supplements on three separate occasions: orally the evening before surgery and either orally or per nasogastric tube on postoperative days 1 and 2. Plasma 25(OH)D concentrations were measured at baseline (the day before surgery and before the first supplement bolus), after surgery on postoperative days 1, 2, 3, and 4, at hospital discharge (5-8 days after surgery), and at an elective outpatient follow-up visit at 6 months. Supplemental vitamin D abolished the acute decrease in 25(OH)D induced by open-heart surgery during postoperative care. Moreover, plasma 25(OH)D gradually increased from baseline to day 3 and remained significantly increased thereafter but plateaued to discharge with supplemental vitamin D. We conclude that perioperative vitamin D supplementation protects against the immediate decrease in plasma 25(OH)D induced by open-heart surgery. ClinicalTrials.gov Identifier: NCT02460211.

Multi-vitamin supplementation blunts the circulating IL-6/IL-10 ratio increase after knee arthroplasty: A randomized, double-blind, placebo controlled study.

Circulating interleukin (IL)-6 and IL-10 concentrations can be elevated following the surgically induced trauma of total knee arthroplasty (TKA). An exaggerated increase in IL-6 relative to IL-10 (i.e., IL-6/IL-10 ratio) associates with trauma severity and indicative of pro-inflammatory predominance. Although various vitamins and minerals alter individual IL-6 and IL-10 concentrations in the blood, surprisingly, it is unknown if a multi-vitamin supplement alters the IL-6/IL-10 ratio during the systemic inflammatory response following TKA. The objective of this study was to identify if a multi-vitamin with mineral supplement taken prior to alters the circulating IL-6/IL-10 ratio following total knee arthroplasty (TKA). This study consisted of a randomized, double-blind, placebo controlled design. Twenty-one subjects undergoing elective, primary, unilateral TKA were randomly assigned to a placebo (PL, n = 11) or multi-vitamin with mineral supplement (MV, n = 10). Supplements were taken daily starting approximately 6-weeks prior to surgery. Supplements were not taken the day of surgery or during inpatient care 2-days after surgery. Circulating IL-6, IL-10, high-sensitivity CRP (hsCRP), vitamin C (ascorbic acid (AA)), vitamin D (25-hydroxyvitamin D (25(OH)D)), and vitamin E (α-tocopherol (αT)) concentrations were measured in fasting blood draw samples obtained ~6-weeks prior to surgery (and before starting supplementation), the morning of surgery, and 24-hours and 48-hours after surgery. MV supplementation tended to increase serum 25(OH)D and significantly increased plasma AA and plasma αT before surgery without mitigating the post-operative IL-6 and hsCRP increases. However, the post-operative increase in the serum IL-6/IL-10 ratio after surgery was significantly blunted in the MV group. Based on these findings, we conclude that a multi-vitamin with mineral supplement taken daily for several weeks before surgery might reduce the pro-inflammatory predominance after TKA. Future research confirming or refuting the novel data presented herein is needed.

Serum cytokines and muscle strength after anterior cruciate ligament surgery are not modulated by high-doses of vitamins E (α- and γ-tocopherol's) and C.

The purpose of this investigation was to identify if supplemental vitamin E (consisting of α- and γ-tocopherol's) and C modulate serum cytokine and muscle strength following an ACL injury and surgery. Subjects were randomly assigned to one of two groups: (1) placebo (n=14) or (2) vitamins E (α-[600m g RRR-α-tocopherol, αT] and γ-[600 mg of RRR-γT]) and C (1000 mg ascorbic acid, AA) (EC; n=15). Supplements were taken daily starting ∼2-wk prior to and concluding 16-wk after surgery. Fasting blood samples were obtained and single-leg peak isometric force measurements were performed at baseline (prior to supplementation), before surgery (∼120-min - blood draw only), and 8-wk, 12-wk, and 16-wk after surgery. αT, γT, AA, and cytokines were measured in each blood sample, and peak isometric force was measured on the injured and non-injured legs separately at each testing session. An exercise protocol consisting of repetitive knee and hip extension and flexion contractions to exhaustion was performed on the injured limb at 16-wk. Vitamin E and C supplementation significantly (all p<0.05) increased plasma αT (∼40%), γT (∼160%), and AA (∼50%) concentrations. Serum cytokine concentrations, peak isometric force, and time to exhaustion during the exercise protocol were not significantly different between groups. Based on these findings, we conclude that vitamin E and C supplementation increases their endogenous levels without minimizing muscular weakness or modulating serum cytokine concentrations after ACL surgery.

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.

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.

γ-Tocopherol-rich supplementation additively improves vascular endothelial function during smoking cessation.

Oxidative stress and inflammation persist years after smoking cessation thereby limiting the restoration of vascular endothelial function (VEF). Although short-term smoking cessation improves VEF, no studies have examined co-therapy of antioxidants in combination with smoking cessation to improve VEF. We hypothesized that improvements in γ-tocopherol (γ-T) status during smoking cessation would improve VEF beyond that from smoking cessation alone by decreasing oxidative stress and proinflammatory responses. A randomized, double-blind, placebo-controlled study was conducted in otherwise healthy smokers (22 ± 1 years; mean ± SEM) who quit smoking for 7 days with placebo (n=14) or γ-T-rich supplementation (n=16; 500 mg γ-T/day). Brachial artery flow-mediated dilation (FMD), cotinine, and biomarkers of antioxidant status, oxidative stress, and inflammation were measured before and after 7 days of smoking cessation. Smoking cessation regardless of supplementation similarly decreased plasma cotinine, whereas γ-T-rich supplementation increased plasma γ-T by seven times and its urinary metabolite γ-carboxyethyl hydroxychroman by nine times (P<0.05). Smoking cessation with γ-T-rich supplementation increased FMD responses by 1.3% (P<0.05) beyond smoking cessation alone (4.1 ± 0.6% vs 2.8 ± 0.3%; mean ± SEM). Although plasma malondialdehyde decreased similarly in both groups (P<0.05), plasma oxidized LDL and urinary F2-isoprostanes were unaffected by smoking cessation or γ-T-rich supplementation. Plasma TNF-α and myeloperoxidase decreased (P<0.05) only in those receiving γ-T-rich supplements and these were inversely related to FMD (P<0.05; R=-0.46 and -0.37, respectively). These findings demonstrate that short-term γ-T-rich supplementation in combination with smoking cessation improved VEF beyond that from smoking cessation alone in young smokers, probably by decreasing the proinflammatory mediators TNF-α and myeloperoxidase.

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.

Vitamins E and C modulate the association between reciprocally regulated cytokines after an anterior cruciate ligament injury and surgery.

OBJECTIVE: : The purpose of this study was to identify the influence of vitamin E and C supplementation on inflammatory cytokines and the association between reciprocally regulated cytokines after anterior cruciate ligament surgery. DESIGN: : A double-blind, placebo-controlled study was conducted in men undergoing anterior cruciate ligament surgery who were randomly assigned to one of two groups (n = 10/group): (1) antioxidant (vitamins E and C) or (2) matching placebos starting ∼2 wks before (baseline) and concluding 3 mos after surgery. Plasma inflammatory cytokines were measured in fasting blood draw samples before and after anterior cruciate ligament surgery. RESULTS: : Plasma interleukin (IL) 1ß concentrations were double at 3 mos after surgery compared with baseline. Plasma IL-1ß increased to a greater (P < 0.05) extent relative to IL-4 in the placebo group (mean ± SE slope, 18.87 ± 0.68; r = 0.97) than in the antioxidant group (mean ± SE slope, 4.84 ± 0.42; r = 0.89). Similarly, the relative increase in IL-1ß to IL-2 was greater (P < 0.05) in the placebo (mean ± SE slope, 2.70 ± 0.21) than in the antioxidant (mean ± SE slope, 1.08 ± 0.23) group. CONCLUSIONS: : Vitamins E and C were ineffective in ameliorating the increases in IL-1ß but altered associations between reciprocally regulated cytokines after anterior cruciate ligament surgery.

Antioxidant supplementation lowers circulating IGF-1 but not F(2)-isoprostanes immediately following anterior cruciate ligament surgery.

Interleukin (IL)-10 is an anti-inflammatory cytokine that suppresses pro-inflammatory cytokines. We previously demonstrated that supplementation with vitamins E and C ameliorated the increase in IL-10 immediately following anterior cruciate ligament (ACL) surgery in the absence of other cytokine perturbations. Since both oxidative stress and insulin-like growth factor-1 (IGF-1) can modulate IL-10 concentrations, the mechanisms for these changes warranted further investigation. Our objective was to evaluate the mechanism for the IL-10 decrease following ACL surgery. This study consisted of randomized, double-blind, placebo-controlled experimental design. Subjects were randomly assigned to daily supplementation with either: (i) antioxidants (AO; vitamins E [alpha-tocopherol] and C [ascorbic acid]; n = 10); or (ii) matching placebos (PL; n = 10). Supplementation started approximately 2 weeks prior to surgery (baseline) and concluded 3 months after surgery. Subjects provided six fasting blood samples at: (i) baseline; (ii) immediately pre-surgery (Pre); (iii) 90 min; (iv) 72 h; (v) 7 days; and (vi) 3 months post-surgery. alpha-Tocopherol, ascorbic acid, F(2)-isoprostane and IGF-1 concentrations were measured in each blood sample. At 90 min relative to other times, plasma F(2)-isoprostane concentrations were significantly (P < 0.05) elevated in both groups, while at 90 min IGF-1 was significantly (P < 0.05) lower in the AO compared to the PL group. The changes in IGF-1 at 90 min relative to baseline were correlated (P < 0.0001) with the changes in IL-10. The decrease in IL-10 observed in the AO group is likely dependent on the decrease IGF-1 since lipid peroxidation was unchanged between the two groups.

Vitamin E and C supplementation does not ameliorate muscle dysfunction after anterior cruciate ligament surgery.

Muscle atrophy and weakness are predominant impairments after anterior cruciate ligament (ACL) surgical repair. We tested the hypothesis that vitamin E and C supplementation will improve recovery from ACL injury. Men undergoing elective ACL surgery were randomly assigned to twice-daily supplements of either antioxidants (AO; vitamins E and C, n=10) or matching placebos (n=10) from 2 weeks before until 3 months after surgery. Each subject provided several fasting blood draws, two muscle biopsies from the thigh muscle of the injured limb, and strength and thigh circumference measurements of the lower limbs. Muscle atrophy was apparent in both groups before and several days after surgery. Compared with baseline measurements, peak isometric force of the injured limb increased significantly (P<0.05) by 3 months postsurgery in both treatment groups; however, AO supplementation did not augment these strength gains. By contrast, baseline plasma ascorbic acid concentrations correlated (r=0.59, P=0.006) with subsequent improvement in the strength of the injured limb. In summary, vitamin E and C supplementation was ineffective in potentiating the improvement in force production by the injured limb; however, baseline vitamin C status was associated with beneficial outcomes in strength, suggesting that long-term dietary habits are more effective than short-term supplements.

Modulation of inflammation by vitamin E and C supplementation prior to anterior cruciate ligament surgery.

Muscle atrophy commonly follows anterior cruciate ligament (ACL) injury and surgery. Proinflammatory cytokines can induce and exacerbate oxidative stress, potentiating muscle atrophy. The purpose of this study was to evaluate the influence of prior antioxidant (AO) supplementation on circulating cytokines following ACL surgery. A randomized, double-blind, placebo-controlled trial was conducted in men undergoing ACL surgery, who were randomly assigned to either: (1) AO (200 IU of vitamin E (50% d-alpha-tocopheryl acetate and 50% d-alpha-tocopherol) and 500 mg ascorbic acid), or (2) matching placebos (PL). Subjects took supplements twice daily for 2 weeks prior to and up to 12 weeks after surgery. Each subject provided five blood samples: (1) baseline (Bsl, prior to supplementation and approximately 2 weeks prior to surgery), (2) presurgery (Pre), (3) 90 min, (4) 72 h, and (5) 7 days postsurgery. Following surgery, inflammation and muscle damage increased in both groups, as assessed by increased circulating IL-6, C-reactive protein, and creatine kinase. During AO supplementation, plasma alpha-T and AA increased while gamma-T concentrations decreased significantly (P< 0.05). At 90 min the AO group displayed a significant decrease in AA, an inverse correlation between AA and (interleukin) IL-8 (r(2)= 0.50, P< 0.05), and a significantly lower IL-10 response than that of the PL group. IL-10 was significantly elevated at 90 min and 72 h in the PL group. In summary, our findings show that circulating inflammatory cytokines increase and AO supplementation attenuated the increase in IL-10 in patients post-ACL surgery.