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Modest and even severe vitamin D deficiency is widely prevalent around the world. There is consensus that a good vitamin D status is necessary for bone and general health. Similarly, a better vitamin D status is essential for optimal efficacy of antiresorptive treatments. Supplementation of food with vitamin D or using vitamin D supplements is the most widely used strategy to improve the vitamin status. Cholecalciferol (vitamin D3) and ergocalciferol (vitamin D2) are the most widely used compounds and the relative use of both products depends on historical or practical reasons. Oral intake of calcifediol (25OHD3) rather than vitamin D itself should also be considered for oral supplementation. We reviewed all publications dealing with a comparison of oral cholecalciferol with oral calcifediol as to define the relative efficacy of both compounds for improving the vitamin D status. First, oral calcifediol results in a more rapid increase in serum 25OHD compared to oral cholecalciferol. Second, oral calcifediol is more potent than cholecalciferol, so that lower dosages are needed. Based on the results of nine RCTs comparing physiologic doses of oral cholecalciferol with oral calcifediol, calcifediol was 3.2-fold more potent than oral cholecalciferol. Indeed, when using dosages ≤ 25 μg/day, serum 25OHD increased by 1.5 ± 0.9 nmol/l for each 1 μg cholecalciferol, whereas this was 4.8 ± 1.2 nmol/l for oral calcifediol. Third, oral calcifediol has a higher rate of intestinal absorption and this may have important advantages in case of decreased intestinal absorption capacity due to a variety of diseases. A potential additional advantage of oral calcifediol is a linear dose-response curve, irrespective of baseline serum 25OHD, whereas the rise in serum 25OHD is lower after oral cholecalciferol, when baseline serum 25OHD is higher. Finally, intermittent intake of calcifediol results in fairly stable serum 25OHD compared with greater fluctuations after intermittent oral cholecalciferol.

Almost two billion people are deficient in key vitamins and minerals, mostly women and children in low- and middle-income countries (LMICs). Deficiencies worsen during pregnancy due to increased energy and nutritional demands, causing adverse outcomes in mother and child, but could be mitigated by interventions like micronutrient supplementation. To our knowledge, this is the first systematic review that aimed to compile evidence from both efficacy and effectiveness trials, evaluating different supplementation interventions on maternal, birth, child health, and developmental outcomes. We evaluated randomized controlled trials and quasi-experimental studies published since 1995 in peer-reviewed and grey literature that assessed the effects of calcium, vitamin A, iron, vitamin D, and zinc supplementation compared to placebo/no treatment; iron-folic (IFA) supplementation compared to folic acid only; multiple micronutrient (MMN) supplementation compared to IFA; and lipid-based nutrient supplementation (LNS) compared to MMN supplementation. Seventy-two studies, which collectively involved 314 papers (451,723 women), were included. Meta-analyses showed improvement in several key birth outcomes, such as preterm birth, small-for-gestational age (SGA) and low birthweight with MMN supplementation, compared to IFA. MMN also improved child outcomes, including diarrhea incidence and retinol concentration, which are findings not previously reported. Across all comparisons, micronutrient supplementation had little to no effect on mortality (maternal, neonatal, perinatal, and infant) outcomes, which is consistent with other systematic reviews. IFA supplementation showed notable improvement in maternal anemia and the reduction in low birthweight, whereas LNS supplementation had no apparent effect on outcomes; further research that compares LNS and MMN supplementation could help understand differences with these commodities. For single micronutrient supplementation, improvements were noted in only a few outcomes, mainly pre-eclampsia/eclampsia (calcium), maternal anemia (iron), preterm births (vitamin D), and maternal serum zinc concentration (zinc). These findings highlight that micronutrient-specific supplementation should be tailored to specific groups or needs for maximum benefit. In addition, they further contribute to the ongoing discourse of choosing antenatal MMN over IFA as the standard of care in LMICs.

Background Use of nutritional supplementation is common in athletes at all levels of sport; however, no study to date has investigated both exercise behaviors and nutrition knowledge. To address this gap in knowledge, this cross-sectional study collected current data on aspects related to exercise behaviors and nutrition knowledge and practices in trained athletes in the United States.Methods Purposive sampling was utilized to recruit participants (n = 667) in the target population. Descriptive statistics were used to summarize data. A chi-square test of independence was performed to examine relationships between selected variables.Results Exercise sessions for respondents were 45–60 min (55.2%) or 90 min (29.4%) with multiple daily workout sessions performed 1–2 (38.5%) for 3–4 days per week (22.5%). Average intensity of cardio sessions was 5 RPE (33.2%) or 6–7 RPE (42.3%), with a similar distribution for strength-based sessions. All respondents reported regular cardio sessions, whereas 10.5% did not regularly engage in strength-based sessions. A majority reported average nutrition knowledge with limited knowledge on amino acids (33.8%) and minerals (32.5%) and advanced knowledge on protein (28.9%), pre-exercise nutrition (27.6%), and training nutrition (27.6%). The nutritional products used daily or often included caffeine (77.6%), electrolytes (55.1%), multi-vitamin (43.0%), and specific vitamins or minerals (46.3%). Products rarely or never used included herbal supplements (74.7%), amino acids (64.5%), and protein powder (50%). Energy gels or similar were used occasionally (48.6%). There was a significant relationship for all pairings of variables with lower level and frequency of soreness associated with higher frequency of recovery activities, higher level and frequency of soreness associated with higher intensity of exercise sessions, and a higher level of nutrition knowledge associated with higher implementation of nutritional focus before, during, and after exercise.Conclusions The present study provides valuable insight into athlete knowledge and behaviors related to exercise and nutrition and highlights the crucial role of knowledge in optimizing nutrition for athletes. These results can be used to inform areas of education needed to improve athletic performance.

Background Special Operations Forces (SOF) often operate in extreme heat, where sustained physical exertion may degrade cognition. Exercise-heat stress can reduce cerebral blood flow (CBF) and oxygenation, increasing the risk of catastrophic errors. While ketone monoesters, such as beta-hydroxybutyrate (BHB), may offer neuroprotective effects by improving CBF and energy metabolism, they have yet to be investigated in the context of hyperthermia. This study compared the effects of BHB to carbohydrate (CHO) on cognitive task performance during exercise-heat stress in endurance-trained individuals.Methods Using a randomized, double-blind, counterbalanced design, 17 male endurance-trained participants (age = 23.8 ± 5.y; VO2max = 58.6 ± 3.2 ml/kg/min) completed two experimental trials. Exercise was performed in a heat chamber (34°C, 45%RH) and included two 45-min treadmill bouts on a 5% grade at 50% velocity at VO2max while wearing a vest (20% body mass [BM]). Participants consumed 4 mg/kg BM of caffeine at the start of each experimental visit. Before each 45-min bout of exercise, participants ingested either 25 g BHB or 25 g CHO (Cluster DextrinTM). Cognitive performance was assessed pre-, mid-, and post-exercise using 60-s reaction time (RT), Object Hit-and-Avoid (OHA), 1-back, and 2-back tests. Change scores were calculated from baseline and were analyzed using repeated measures ANOVA. Holm-corrected post-hoc analyses were used for significant interactions or main effects (α = 0.05). Effect sizes were calculated as Cohen’s d.Results RT was unchanged across time and conditions. OHA accuracy increased over time (p < 0.01), but did not differ between conditions. Post hoc testing revealed that accuracy increased from pre- to mid-exercise (+2.4%, p = 0.01, d = 0.7), and from pre- to post-exercise (+2.6%, p = 0.01, d = 0.8). In the 1-back, a main effect of condition was observed for target accuracy (BHB > CHO +12.6%, p = 0.04, d = 0.9), with a significant interaction indicating greater improvements at post-exercise for BHB versus CHO in both target (+23.4%, p = 0.03, d = 0.9) and total accuracy (+3.3%, p = 0.03, d = 0.7). In contrast, target accuracy declined in CHO at post-exercise (−12.3%, p = 0.03, d = 1.0). For the 2-back, the BHB condition resulted in higher total accuracy (+2.2%, p = 0.03, d = 0.8) and target accuracy (+13.8%, p = 0.02, d = 0.3) compared to CHO.Conclusions BHB ingestion may benefit working memory during exercise-heat stress, as evidenced by performance on the 1-back and 2-back. However, no differences were observed in RT or OHA performance, suggesting the benefits of BHB supplementation may be task-specific and most evident during more complex cognitive tasks. These findings indicate that BHB may selectively support some relevant cognitive domains in extreme environments, such as those faced by SOF.

Coenzyme Q10 (CoQ10) is necessary for mitochondrial electron transport. Mutations in CoQ10 biosynthetic genes cause primary CoQ10 deficiency (PCoQD) and manifest as mitochondrial disorders. It is often stated that PCoQD patients can be treated by oral CoQ10 supplementation. To test this, we compiled all studies describing PCoQD patients up to May 2022. We excluded studies with no data on CoQ10 treatment, or with insufficient description of effectiveness. Out of 303 PCoQD patients identified, we retained 89 cases, of which 24 reported improvements after CoQ10 treatment (27.0%). In five cases, the patient's condition was reported to deteriorate after halting of CoQ10 treatment. 12 cases reported improvement in the severity of ataxia and 5 cases in the severity of proteinuria. Only a subjective description of improvement was reported for 4 patients described as responding. All reported responses were partial improvements of only some symptoms. For PCoQD patients, CoQ10 supplementation is replacement therapy. Yet, there is only very weak evidence for the efficacy of the treatment. Our findings, thus, suggest a need for caution when seeking to justify the widespread use of CoQ10 for the treatment of any disease or as dietary supplement.

Folate is a water‐soluble B‐vitamin and enzymatic cofactor that is necessary for the synthesis of purine and thymidine nucleotides and for the synthesis of methionine from homocysteine. Impairment of folate‐mediated one‐carbon metabolic pathways can result from B‐vitamin deficiencies and/or single nucleotide polymorphisms, and increases risk for pathologies, including cancer and cardiovascular disease, and developmental anomalies including neural tube defects. Although several well validated metabolic and genomic biomarkers for folate deficiency exist, our understanding of the biochemical and genetic mechanisms whereby impaired folate metabolism increases risk for developmental anomalies and disease is limited, as are the mechanisms whereby elevated folate intake protects against these pathologies. Therefore, current initiatives to increase folate intakes in human populations to ameliorate developmental anomalies and prevent disease, while effective, lack predictive value with respect to unintended adverse outcomes.

Low levels of vitamin D are a widespread global issue. This study aimed to determine the optimal vitamin D3 supplementation dose for healthy young adults by comparing the effectiveness of gradually increasing cholecalciferol doses over two years. Thirty-five volunteers participated in a two-season pilot study conducted from October to April to avoid sunlight-induced vitamin D3 synthesis. The participants used oil-based drops of cholecalciferol, increasing their dose from 1,000 to 2,000, 4,000, and then 8,000 IU daily for 60 days with a 30-day break. Supplementing with 1,000 IU/day raised vitamin D levels to the recommended range (above 75 nmol/l), but levels dropped below this range after a 30-day break. A dose of 2,000 IU/day maintained vitamin D levels within the recommended range, even after the break. Increasing the dose to 4,000 IU/day produced a rapid rise, though levels dropped more significantly after stopping supplementation. With 8,000 IU/day, both the rise and subsequent decline in vitamin D levels were more pronounced. Effective vitamin D supplementation in healthy young adults can be achieved with a daily dose of 2,000 IU during winter. However, 4,000 IU/day was more effective for maintaining levels above 100 nmol/l, supporting broader health benefits. Regular monitoring of [25(OH)D], calcium, and phosphorus levels is essential.

BackgroundMultiple sclerosis (MS) is a chronic immune-mediated neurodegenerative disorder of the central nervous system and a leading cause of disability among young adults. The disease exhibits considerable heterogeneity in clinical progression, with some patients experiencing more aggressive disease activity and a rapid decline in quality of life. Vitamin D plays a key role in immune regulation, and evidence suggests that its deficiency constitutes a significant environmental risk factor for immune-mediated conditions such as MS. While there are controversies regarding the role of serum 25(OH)D in MS as well as vitamin D3 supplements in controlling relapse and disability improvement during treatment. Therefore, our current meta-analysis aims to examine the relationship between serum 25(OH)D levels—and their modulation through supplementation—and multiple sclerosis.MethodsComprehensive literature review was performed from conception to November 17, 2025, employing various online databases including PubMed, Cochrane Library, Web of Science, and EMBASE. The relevant studies about MS and serum 25-hydroxyvitamin D (25(OH)D) level or vitamin D3 supplementation. This meta-analysis incorporated 40 research examining the correlation between serum 25(OH)D levels and multiple sclerosis, as well as 22 studies investigating the effects of vitamin D3 supplementation on multiple sclerosis.Results1) The 25(OH)D levels in patients with MS were significantly lower than those in healthy controls. In the analysis of disease subtypes, patients with relapsing-remitting MS (RRMS) had significantly higher 25(OH)D levels than those with secondary progressive MS (SPMS), but no significant difference was observed compared to patients with primary progressive MS (PPMS). Additionally, RRMS patients had significantly lower 25(OH)D levels during relapse than during remission. No significant seasonal fluctuation in 25(OH)D levels was observed in MS patients; 2) Multivariable-adjusted analysis comparing the highest versus lowest serum 25(OH)D categories revealed that higher serum 25(OH)D levels were associated with a lower risk of MS onset and lower disability scores (EDSS), but no significant association was found with disease activity. 3) In the intervention analysis, overall, vitamin D3 supplementation did not significantly reduce the annualized relapse rate (ARR) or improve EDSS scores. However, subgroup analysis indicated that high-dose vitamin D3 supplementation significantly reduced the ARR, whereas low-dose supplementation showed no such effect. Multivariable-adjusted analysis further confirmed that vitamin D3 supplementation was significantly associated with a reduced risk of MS relapse, and this benefit was similarly observed only in the high-dose supplementation group.ConclusionsThis systematic analysis confirms that patients with MS exhibit significantly lower serum 25(OH)D levels compared to healthy controls, with notable reductions observed during clinical relapses. A clear gradient exists across disease subtypes, with RRMS patients showing higher levels than those with SPMS. An inverse correlation was demonstrated between serum 25(OH)D levels and both the risk and severity of MS. Critically, while high-dose vitamin D3 supplementation is associated with a reduced ARR and overall relapse risk, neither supplementation compared to placebo nor dosage comparison significantly affected relapse rates during the study period or final disability scores. These findings suggest a complex, dose-dependent role of vitamin D in modifying relapse risk without a clear impact on short-term disability progression in established MS.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/login, identifier CRD420251273119.

L-serine plays an essential role in a broad range of cellular functions including protein synthesis, neurotransmission, and folate and methionine cycles and synthesis of sphingolipids, phospholipids, and sulphur containing amino acids. A hydroxyl side-chain of L-serine contributes to polarity of proteins, and serves as a primary site for binding a phosphate group to regulate protein function. D-serine, its D-isoform, has a unique role. Recent studies indicate increased requirements for L-serine and its potential therapeutic use in some diseases. L-serine deficiency is associated with impaired function of the nervous system, primarily due to abnormal metabolism of phospholipids and sphingolipids, particularly increased synthesis of deoxysphingolipids. Therapeutic benefits of L-serine have been reported in primary disorders of serine metabolism, diabetic neuropathy, hyperhomocysteinemia, and amyotrophic lateral sclerosis. Use of L-serine and its metabolic products, specifically D-serine and phosphatidylserine, has been investigated for the therapy of renal diseases, central nervous system injury, and in a wide range of neurological and psychiatric disorders. It is concluded that there are disorders in which humans cannot synthesize L-serine in sufficient quantities, that L-serine is effective in therapy of disorders associated with its deficiency, and that L-serine should be classified as a “conditionally essential” amino acid.

Background: Despite recent evidence demonstrating iron and folate supplementation reduces the risk of low birth weight and preterm births, synthesis of the evidence is not sufficient to understand their impacts in Africa. Method: MEDLINE, PsycINFO, Embase, Scopus, CHINAL, Web of Science, Cochrane databases, and Google Scholar were searched for the published and grey literature. Either iron-only, folate-only, or iron–folic acid (IFA) oral supplementation during pregnancy was the primary exposure/intervention. The focus of this review was low birth weight and preterm births in the African region. Qualitative synthesis, meta-analysis, and subgroup analysis were employed. Results: In the qualitative synthesis (n = 4), IFA supplementation showed a positive impact on reducing preterm birth. Additionally, the meta-analysis showed that IFA and iron-only supplementation reduced the odds of low birth weight by 63% (OR 0.37; 95% CI: 0.29, 0.48) and 68% (OR 0.32; 95% CI: 0.21 to 0.50), respectively. Conclusion: Both iron-only and IFA supplementation are effective in reducing the risk of low birth weight in Africa. There is also promising evidence suggesting a potential reduction in preterm births. Consequently, further research is needed, particularly targeting high-risk groups such as women residing in rural areas with limited support and low levels of literacy.