P011 Effect size of vitamin-C on indices of sleep-quality, fatigue, endothelial-function, circulating HIF-1alpha and patient mortality: a systematic review

Background-Patients-with-untreated-or-undiagnosed-disordered-breathing have increased-risk-of-perioperative-complications. Increased-vitamin-C was-associated with-improved-quality-of-sleep. Furthermore, supplemental-vitamin-C has been associated with-reduced-fatigue, improved-endothelial-function, and regulation-of-HIF-1α-expression-and-reactive-oxygen-species(ROS). Administration of supplemental-vitamin-C-to-patients-treated-for-life-threatening-disease-states-with-excessive-ROS was associated-with-lowered-mortality. Since patients scheduled for elective-surgery have-a-risk of untreated-or-undiagnosed-sleep-disorder such as OSA; the hypothesis emerged that administering-supplemental-vitamin-C during the pre-operative period to people with high-STOP-BANG-scores maybe associated with lower-levels of perioperative-adverse-events. The objective of this study was to quantify the effect-sizes of vitamin-C for promoting sleep-quality, reducing-fatigue, regulating endothelial-function and circulating HIF-1α-expression, lowering mortality amongst people treated for life-threatening conditions associated with high-levels of ROS; and the impact of untreated-or-undiagnosed-OSA on peri-operative adverse-events. Methods-A Prospero-registered(ID 262766) systematic-review in accordance with the PRISMA-2020-statement was undertaken using Comprehensive-Meta-Analysis-software to quantify effect-sizes of vitamin-C and OSA on-patient-outcomes. Progress to date-Four-studies were identified examining-the-impact-of-higher-levels-of-vitamin-C on sleep-quality, Hedges’ g=0.384(95%CI-0.180-to-0.588),p<0.001. Eleven-studies were identified examining the impact-of-supplemental-vitamin-C on fatigue. Hedges’ g=0.484(95%CI-0.314-to-0.653), p<0.001. Five-studies explored the impact of supplemental-vitamin-C on improved-endothelial-function. Hedges’ g = 0.988(95%CI-0.516-to-1.461), p<0.001. Five-studies examined the-impact-of-supplemental-vitamin-C on reducing-HIF-1α-expresion. Hedges’g=4.282(95%CI-2.482-to-6.066), p<0.001. Sixty-seven studies comparing-the-impact of supplemental-vitamin-C on mortality, OR=0.706(95%CI-0.615-to-0.810), p<0.001. Fourteen-studies-compared the odds of perioperative-adverse-events amongst patients at high-risk-of-OSA with controls; OR = 2.687(95%CI-1.705-to-4.233), p<0.001). Intended Outcome and Impact-Statistically-and-clinically-significant-evidence was-observed-supporting the hypothesis that-the-biology-of-abnormal-sleep-states could be regulate-by supplemental-vitamin-C; and untreated-or-undiagnosed-OSA was associated with increased-perioperative-adverse events. Due to the-lack-of-clinical-equipoise regarding supplemental-vitamin-C promoting-healthy-sleep, regulate-the-pathological-impacts of intermittent-hypoxaemia and oxidative-stress, future-ethical-research will require all-eligible-subjects to-be-offered vitamin-C. Prospective-supplemental-vitamin-C-treated-groups could be compared with historic-controls; or standard pre-operative-care and standard pre-operative-care-plus supplemental-vitamin-C could be randomised according to surgical-centre to promote ethical-clinical-investigation. These experimental-design-considerations also have implications for improving-clinical-governance in the current-era-of-fiscal-restraint.

Combined Supplementation with Vitamin B-6 and Curcumin is Superior to Either Agent Alone in Suppressing Obesity-Promoted Colorectal Tumorigenesis in Mice

ABSTRACT Background Obesity increases the colorectal cancer risk, in part by elevating colonic proinflammatory cytokines. Curcumin (CUR) and supplemental vitamin B-6 each suppress colonic inflammation. Objectives We examined whether the combination of CUR and vitamin B-6 amplifies each supplement's effects and thereby suppress obesity-promoted tumorigenesis. Methods Male Friend Virus B (FVB) mice (4-week-old; n = 110) received 6 weekly injections of azoxymethane beginning 1 week after arrival. Thereafter, they were randomized to receive a low-fat diet (10% energy from fat), a high-fat diet (HFD; 60% energy from fat), a HFD containing 0.2% CUR, a HFD containing supplemental vitamin B-6 (24 mg pyridoxine HCl/kg), or a HFD containing both CUR and supplemental vitamin B-6 (C + B) for 15 weeks. Colonic inflammation, assessed by fecal calprotectin, and tumor metrics were the primary endpoints. The anti-inflammatory efficacy of the combination was also determined in human colonic organoids. Results HFD-induced obesity produced a 2.6-fold increase in plasma IL-6 (P < 0.02), a 1.9-fold increase in fecal calprotectin (P < 0.05), and a 2.2-fold increase in tumor multiplicity (P < 0.05). Compared to the HFD group, the C + B combination, but not the individual agents, decreased fecal calprotectin (66%; P < 0.01) and reduced tumor multiplicity and the total tumor burden by 60%–80% (P < 0.03) in an additive fashion. The combination of C + B also significantly downregulated colonic phosphatidylinositol-4,5-bisphosphate 3-kinase, Wnt, and NF-κB signaling by 31%–47% (P < 0.05), effects largely absent with the single agents. Observations that may explain how the 2 agents work additively include a 2.8-fold increased colonic concentration of 3-hydroxyanthranillic acid (P < 0.05) and a 1.3-fold higher colonic concentration of the active coenzymatic form of vitamin B-6 (P < 0.05). In human colonic organoids, micromolar concentrations of CUR, vitamin B-6, and their combination suppressed secreted proinflammatory cytokines by 41%–93% (P < 0.03), demonstrating relevance to humans. Conclusions In this mouse model, C + B is superior to either agent alone in preventing obesity-promoted colorectal carcinogenesis. Augmented suppression of procancerous signaling pathways may be the means by which this augmentation occurs.

Effect of Dietary or Supplemental Vitamin C Intake on Vitamin C Levels in Patients with and without Cardiovascular Disease: A Systematic Review

Atherosclerosis is a pro-oxidative and pro-inflammatory disease state, which is the underlying cause of most cardiovascular events, estimated to affect 5.2% of the Australian population. Diet, and specifically vitamin C, through its antioxidant properties can play a role in impeding the development and progression of atherosclerosis. This systematic review conducted comprehensive searches in Medline, Emcare, Scopus, PubMed, and Cochrane using key search terms for vitamin C, plasma vitamin C, supplementation, and cardiovascular disease (CVD). The results demonstrated that vitamin C supplementation resulted in a significant increase in vitamin C levels in populations with or without CVD, except for one study on the CVD population. It was also seen that the healthy population baseline and post-intervention vitamin C levels were high compared to the CVD population. However, further research is indicated for CVD population groups with varying baseline vitamin C levels, such as low baseline vitamin C, within a more representative elderly cohort in order to formulate and update vitamin C repletion guidelines.

Effects of Vitamin D3 Supplementation on Body Composition in the VITamin D and OmegA-3 TriaL (VITAL)

Context Although observational studies show inverse associations between vitamin D status and body weight/adiposity, there are few large randomized controlled trials (RCTs) investigating this relationship. Objective To determine whether vitamin D3 supplementation lowers weight or improves body composition. Design The VITamin D and OmegA-3 TriaL (VITAL) was a double-blinded, placebo-controlled RCT including 25,871 U.S. adults. This ancillary study was completed in a sub-cohort that underwent body composition assessments at baseline and 2-year follow-up (89% retention). Setting Harvard Clinical and Translational Science Center in Boston Participants 771 participants (men ≥50 and women ≥55 years) Interventions 2x2 factorial design of supplemental vitamin D3 (2000 IU/day) and/or omega-3 fatty acids (1 g/day) Main Outcome Measures Endpoints were 2-year changes in weight, body mass index (BMI), waist circumference, and total and/or regional fat and lean tissue measures determined by dual-energy X-ray absorptiometry. Effect modification by clinical variables and total and free 25-hydroxyvitamin D (25[OH]D) levels was explored. Results There were no effects of supplemental vitamin D3 versus placebo on weight, BMI, or measures of adiposity and lean tissue. Effects did not vary by sex, race/ethnicity, fat mass index, or baseline total or free 25(OH)D levels. Vitamin D3 supplementation did slightly improve body fat percentage in participants with normal BMI at baseline, but not in the overweight or obese (p for interaction=0.04). Conclusions Daily vitamin D3 supplementation versus placebo in the general older population did not improve weight or body composition. Whether supplemental vitamin D3 may benefit individuals with normal BMI warrants further study.

Distribution of injected fat-soluble vitamins in plasma and tissues of nursery pigs

Objective: The objective of this experiment was to investigate the effects of fat-soluble vitamin injection on plasma and tissue vitamin status in nursery pigs.Methods: A total of 16 pigs (initial body weight: 7.15±1.1 kg) were allotted to 2 treatments at d 7 post-weaning. Pigs were fed a corn-soybean meal-based basal diet with no supplemental vitamin A and i.m. injected with 300,000 IU of retinyl palmitate, 900 IU of d-α-tocopherol and 30,000 IU of vitamin D₃ with control pigs having no vitamin injection. Blood (d 0, 3, 7, and 14 post-injection) and tissue samples (liver, brain, heart, lung, and muscle; d 7 and 14 post-injection) were collected from pigs. Retinyl palmitate, retinol, and α-tocopherol concentrations were analyzed in plasma and tissues, while plasma was assayed for 25-hydroxycholecalciferol (25-OHD₃).Results: Plasma retinol and 25-OHD₃ concentrations increased by the vitamin injection from d 3 to 14 post-injection (p<0.05) whereas plasma retinyl palmitate was detected only in the vitamin treatment at d 3 and 7 post-injection (115.51 and 4.97 μg/mL, respectively). Liver retinol, retinyl palmitate, and retinol+retinyl palmitate concentrations increased by retinyl palmitate injection at d 7 and 14 post-injection (p<0.05) whereas those were not detected in the other tissues. The d-α-tocopherol injection increased α-tocopherol concentrations in plasma at d 3 and 7 post-injection (p<0.05) and in liver, heart (p<0.10), and muscle (p<0.05) at d 7 post-injection.Conclusion: Fat-soluble vitamin injection increased plasma status of α-tocopherol, retinol, retinyl palmitate and 25-OHD₃. As plasma levels decreased post-injection, vitamin A level in liver and vitamin E level in muscle, heart and liver increased. The α-tocopherol found in plasma after injection was distributed to various tissues but retinyl palmitate only to the liver.

Association Between Vitamin D and Hyperuricemia Among Adults in the United States

Background: Serum uric acid can act as a risk factor for cardiovascular disease (CVD) and as antioxidant defense. Vitamin D deficiency can activate the parathyroid to induce the release of parathyroid hormone, which was thought to increase serum uric acid level, and low vitamin D status may also be associated with risk of CVD. No known studies have explored the association between serum 25(OH) D, vitamin D intake, and HU for the American population.Methods: We extracted 15,723 US adults aged 20–85 years from the National Health and Nutrition Examination Survey (NHANES) in 2007–2014. All dietary intakes were evaluated through 24-h dietary recalls. Multivariable logistic regression analysis was performed to examine the associations after adjustment for confounders.Results: Compared to the lowest quintile (Q1), for males, adjusted odds ratios (ORs) of HU in Q2 to Q4 of serum 25(OH) D levels were 0.78 (95% CI, 0.65–0.93), 0.97 (0.81–1.16), and 0.72 (0.60–0.88); ORs in Q2–Q5 of total vitamin D intake were 0.83 (0.69–0.98), 0.69 (0.58–0.83), 0.66 (0.55–0.79), and 0.59 (0.48–0.71), respectively. In females, OR was 0.80 (0.66–0.97) of serum 25(OH) D for Q3, and ORs in Q5 of total vitamin D intake were 0.80 (0.65–0.98).Conclusions: Our findings indicated that the serum 25(OH) D intakes of dietary vitamin D, supplemental vitamin D, and total vitamin D were inversely associated with HU in males. In females, a lower risk of HU with higher serum 25(OH) D, dietary vitamin D, and total vitamin D intake was found, but with no association between supplemental vitamin D intake and the risk of HU.

VITamin D and OmegA-3 TriaL (VITAL): Effects of Vitamin D Supplements on Risk of Falls in the US Population

Context It is unclear whether vitamin D supplementation reduces risk of falls, and results from randomized controlled trials (RCTs) are conflicting. Objective The objective of this work is to determine whether 2000 IU/day of supplemental vitamin D3 decreases fall risk. Design VITamin D and OmegA-3 TriaL (VITAL) is a double-blind, placebo-controlled RCT including 25 871 adults, randomly assigned November 2011 to March 2014 and treated for 5.3 years (median). Setting This is a nationwide study. Participants Men 50 years or older and women 55 years or older (mean age, 67.1 years) without cancer or cardiovascular disease at baseline participated in this study. Interventions Interventions included vitamin D3 (cholecalciferol; 2000 IU/day) and/or omega-3 fatty acids (1 g/day) or respective placebos in a 2 × 2 factorial design. Main Outcome Measures Main outcome measures include 2 or more falls and falls resulting in a doctor or hospital visit. Results Baseline serum total 25-hydroxyvitamin D (25[OH]D) level was 77 nmol/L; characteristics were well-balanced between groups. Numbers of participants with 2 or more falls were similar between active and placebo groups (9.8% vs 9.4%). Over 5 years, there were no differences in the proportion having 2 or more falls (odds ratio [OR] = 0.97; 95% CI, 0.90-1.05, P = .50), falls resulting in a doctor visit (OR = 1.03; 95% CI, 0.94-1.13, P = .46), or resulting in a hospital visit (OR = 1.04; 95% CI, 0.90-1.19, P = .61) between groups. Results did not differ between those with baseline 25(OH)D less than 50 vs 50 nmol/L or greater or other cut points. Conclusion Daily supplemental vitamin D3 vs placebo did not decrease fall risk in generally healthy adults not selected for vitamin D insufficiency. This large RCT does not indicate that supplemental vitamin D should be used for primary prevention of falls in the US population.