Supplementation In Older Adults Research Articles

Improvements to mood, stress and loneliness following 12-week multivitamin supplementation in older adults: a randomised, placebo-controlled, trial.

Research has indicated the potential for multivitamin-mineral (MVM) supplementation to improve aspects of wellbeing and cognitive function in older adults via a range of biological mechanisms. However, outside of cognitive function and mood, this research rarely assesses other outcomes that are pertinent to the daily lives of older adults. The current study aimed to investigate the effectiveness of a MVM supplement on meaningful outcomes of everyday functioning in older adults. This randomised, double-blind, placebo-controlled, parallel groups trial investigated the effects of 12-week MVM supplementation on measures of wellbeing, mood, and memory; physical health and activity; and social interaction and loneliness. Outcomes were measured at baseline and after 12 weeks in a sample of 228 (124 female) older adults ( > 70 years). MVM supplementation had no effect on the primary outcome of wellbeing (p = 0.29 in males, p = 0.421 in females), but led to increased feelings of friendliness in females (p = 0.045). In males, following MVM, there were lower levels of prolonged stress reactivity (p = 0.007), lower overall stress reactivity (p = 0.019), and lower emotional loneliness (p = 0.042). This study provides novel evidence of increased friendliness and decreased stress reactivity and loneliness following MVM supplementation in older adults. These findings support the exploration of broader functions pertinent to aspects of daily living in older adults. Sex differences in response highlight the importance of exploring effects in men and women separately and support a recommendation for the inclusion of diverse samples in future research that are representative of the population.

Personalized approaches to the prescription of protein-based oral nutritional supplements in older adults: A scoping review

Personalized approaches to the prescription of protein-based oral nutritional supplements in older adults: A scoping review

Resistance Training and Nutritional Supplementation in Older Adults with Sarcopenia after Acute Disease: A Feasibility Study.

Resistance exercise and protein supplementation are recognized as effective treatment strategies for age-related sarcopenia; however, there are limited data on their feasibility, tolerability, and safety. The primary outcome of this study was feasibility, evaluated through the 15-item TELOS (Technological, Economics, Legal, Operational, and Scheduling) feasibility components and by recruitment, retention, and consent rates. Tolerability was measured by examining permanent treatment discontinuation, treatment interruption, exercise dose modification, early termination, rescheduling of missed sessions, losses to follow-up, attendance, and nutritional compliance. Safety was evaluated using the parameters provided by the European Medicines Agency, adapted for exercise interventions. Thirty-two subjects were recruited (average age 81.6 [SD 9.3] years). The TELOS components were assessed before the intervention; out of 15 questions relevant for successful implementation, 4 operational needs answers required specific actions to prevent potential barriers. The recruitment rate was 74%. Eleven patients (34.4%) had permanent treatment interruption (retention rate = 65.6%). Patients attended a mean of 23 (SD 12.0) exercise sessions, with a mean of 56 (SD 32.6) nutritional compliances. A total of 21 patients (65.6%) experienced adverse events unrelated to the intervention, while 7 patients (21.9%) presented adverse reactions to strength exercise. The main barriers to feasibility were operational components and recruitment challenges. Although the intervention was generally safe, the high rate of probable adverse effects, unrelated to the intervention but associated with the individual's baseline health condition, may affect adherence to treatment programs of this kind.

Evaluating the Role of Probiotics, Prebiotics, and Synbiotics Supplementation in Age-related Musculoskeletal Disorders in Older Adults: A Systematic Review.

The aim of this systematic review is to evaluate musculoskeletal changes in response to prebiotics, probiotics, or synbiotics supplementation in older adults or in animal models of aging musculoskeletal disorders. A comprehensive search was conducted on electronic databases, including PubMed/Medline, Cochrane, and Web of Science until April 2024. The quality assessment of clinical trials was conducted using the Cochrane Collaboration tool and for animal studies, the SYRCLE's tool was used. Our literature search resulted in 652 studies. After removing duplicates and screening the articles based on their titles and abstracts, we assessed the full text of 112 articles, which yielded 20 clinical trials and 30 animal studies in our systematic review. Most of human and animal studies reported an improvement in physical performance, a decrease in frailty index, and a lower reduction in bone mineral density in the intervention groups. Body composition tends to increase in muscle ratio, muscle mass, and reduce in appendicular lean mass and muscle atrophy. Also, the intervention induced bone turnover and mineral absorption, significantly increasing Ca, P, and Mg absorption and short-chain fatty acid concentration. Additionally, levels of inflammatory markers such as IL1, IL6, IL17, T helper 17, and TNF-α exhibited a decreasing trend, while an increase in IL10 and IFN-γ was observed. Prebiotics, probiotics, or synbiotics supplementations could effectively improve the physical performance and muscle strength and reduce the risk of bone loss and frailty in the elderly.

The Effect of β-Hydroxy-β-Methylbutyrate on Muscle Strength and Functional Outcomes in Older Adults

Nutritional intervention is increasingly being recognized as playing an important role in functional status. The supplementation with β‑hydroxy-β-methylbutyrate (HMB), which is a metabolite of an essential amino acid, may be an effective nutritional intervention to improve muscle strength and functionality in older adults. The aim of this narrative review was to present an updated overview of the effects of HMB supplementation in older adults, specifically on muscle strength and functional outcomes. A PubMed database search was performed and only randomized controlled trial studies were included. More than half of the 14 analyzed studies reported that HMB supplementation improved muscle strength and other functional outcomes. HMB supplementation has demonstrated some promising effects on muscle strength and functional outcomes in older adults with different conditions of health and physical activity.

Association of Plasma n-3 Polyunsaturated Fatty Acid Levels and the Prevalence of Frailty in Older Adults: A Cross-Sectional Analysis of UK Biobank.

Circulating levels of n-3 polyunsaturated fatty acids (PUFAs) have been associated with frailty among Koreans (a population with a high intake of fish), but whether this association exists in Western populations with low fish intake is unknown. The present study examined the hypothesis that the prevalence of frailty was inversely associated with plasma levels of n-3 PUFAs, with the intake of oily fish, and with fish oil supplementation in older adults in the United Kingdom. UK Biobank including 79 330 adults aged ≥65 years with dietary data, and 18 802 participants with plasma fatty acid data were used. Frailty was defined using the Cardiovascular Health Study index, plasma levels of n-3 PUFAs were measured by nuclear magnetic resonance, and intake of oily fish and/or fish oil supplements was collected via food frequency questionnaire. Frailty prevalence was inversely associated with n-3 PUFA levels [odds ratios (OR) per SD: 0.86, 95% confidence interval (CI) 0.79-0.94; p < .001], with oily fish intake (never vs ≥2 servings per week; OR 0.59, 95% CI 0.52-0.68, p < .001), and with the use of fish oil supplements (OR 0.72; 95% CI 0.66-0.78; p < .001) after adjusting for confounding factors. All 3 exposures were also associated with each frailty criterion, particularly low physical activity and walking pace. Inverse associations between plasma n-3 PUFA levels and measures of frailty suggest that higher intakes of oily fish or the use of fish oil supplements may help prevent frailty in older adults in the United Kingdom.

Tolerability of glutamine supplementation in older adults: a double-blind placebo-controlled randomized clinical trial.

In this double-blind placebo-controlled randomized investigation, we assessed the tolerability of glutamine in older adults recruited from three daycare centers. The relevance of studying glutamine supplementation in elderly patients lies in its potential to provide a well-tolerated intervention. Glutamine, a crucial amino acid, plays a vital role in various physiological processes, including immune function and protein synthesis. Understanding its impact on older adults is essential, given the potential implications for their health and well-being. Participants received a daily dose of 12.4 g of oral effervescent glutamine (EGln group) or maltodextrin (placebo group) for 60 days. Fifteen patients from each group completed the study. The mean ages were 77.0±9.1 and 79.0±6.9 years for the EGln and placebo groups, respectively. We evaluated body mass index, aminogram, hemogram, plasma levels of glucose, prealbumin, albumin, urea, creatinine, uric acid, C-reactive protein, vitamin D, calcium, sodium, potassium, and the plasma activities of aspartate aminotransferase and alanine aminotransferase. Notably, we quantified a broad array of inflammatory markers and growth factors providing a holistic understanding of the potential effects of glutamine supplementation. The results demonstrated that oral glutamine did not induce significant changes in any evaluated parameters, and no adverse effects were reported. This finding suggested that the dosage of glutamine used in this study was well-tolerated and safe. This information contributes to the broader understanding of glutamine supplementation, emphasizing its safety and supporting its potential as a viable intervention for maintaining health in aging individuals.

Whey Protein Supplementation in Older Adults With Type 2 Diabetes Undergoing a Resistance Training Program: A Double-Blind Randomized Controlled Trial.

This study aims to analyze the effect of whey protein (WP) supplementation on glycemic control, muscle strength, quality of life, and body composition in older adults with non-insulin-dependent diabetes undergoing a resistance training program. A double-blind, placebo-controlled, randomized study was carried out with older adults with Type 2 diabetes. Body composition, food intake, muscle strength, glycemic profile, markers of renal function, cardiopulmonary capacity, and quality of life were evaluated. Older adults were randomized into a supplementation group with 33g of WP consumed twice a week on days of resistance training for 12weeks supplemented group and a placebo group. In total, 39 older adults were randomized into two groups, 19 in the supplement group and 20 in the placebo group. Both groups showed improvement in muscle strength, with the WP group failing to exceed that of the control group. WP supplementation slightly increased blood urea compared with the placebo group (p = .05), but values remained within normal limits. The group that used WP showed a small improvement in mental health, according to the 12-Item Short-Form Health Survey questionnaire, but without clinically important improvements. Both groups showed improvements in muscle strength and mass, regardless of supplementation, showing that resistance exercises performed twice a week can contribute to the nonprogression of sarcopenia in older adults with Type 2 diabetes. More studies are needed to determine the safe and effective amount of supplementation to improve muscle strength without renal impairment in older adults with diabetes.

Improved Muscle Mass and Function With Protein Supplementation in Older Adults With Sarcopenia: A Meta-Analysis.

: To systematically review the effects of protein supplementation in older adults with sarcopenia. : A systematic literature search was conducted in PubMed, Cochrane Library, and Embase databases until May 2023. The inclusion criteria were as follows: (1) randomized controlled trials with a quantitative study design; (2) studies with a study group of older adults with sarcopenia; (3) studies comparing muscle mass, muscle strength, and performance of older adults with sarcopenia after protein supplementation; and (4) studies published up to May 2023. : Six retrospective comparative studies, including 715 patients, met the inclusion criteria. The nutritional supplementation group exhibited significant improvement in appendicular skeletal muscle mass (standardized mean difference [SMD]=0.41; 95% confidence interval [CI], 0.24-0.58; p<0.001; I2=1%), while handgrip strength (SMD=0.37; 95% CI, -0.32-1.07; p=0.29; I2=94%) and Short Physical Performance Battery (SPPB) (SMD=0.35; 95% CI, -0.47-1.18; p=0.40; I2=94%) showed a tendency for improvement. : Nutritional supplementation with protein increased appendicular muscle mass in older adults with sarcopenia and improved handgrip strength and SPPB scores.

39 An audit of Vitamin D status in acute medical patients over the age of 65

Abstract Background Vitamin D is an essential nutrient for older adults in maintaining bone health, prevention and treatment of osteoporosis. It plays a fundamental role in preventing fractures. Vitamin D is seasonal, meaning it is not made during winter, and in summer is subject to the variable sunlight available in Ireland. The Department of Health Guidance in 2020 recommended adults over 65 years should be supplemented with 15 micrograms of Vitamin D daily. 55.5% of adults over 65 years have insufficient/deficient vitamin D levels in winter. The aim of the audit was to highlight the significance of routine Vitamin D testing and its management in all acute medical patients over 65 years. Methods A prospective audit of 50 patients aged over 65 years was conducted between December 2022 and March 2023. The data collected were Vitamin D serology results, the presence and type of Vitamin D supplement prescribed, whether the Vitamin D level was mentioned in discharge letters, and if any patient presented with osteoporotic fractures. Results 48% of older adults were not on any Vitamin D supplement. 64% had insufficient Vitamin D levels of which 32% were truly deficient. Of those insufficient/inadequate of Vitamin D, 44% were not on any Vitamin D. Additionally, only 18% of Vitamin D results were mentioned in medical discharge letters. Overall, 30% of older adults presented with fractures and yet 10% of those were not on Vitamin D. Conclusion The audit highlighted the lack of Vitamin D supplementation in older adults. The results revealed insufficient monitoring of Vitamin D levels leading to deficiencies and correlating with presentations with fractures. All of this is detrimental to the older adult population. Highlighting the vital role of Vitamin D in bone health among clinicians and improving communication with colleagues are important areas for improving practice.

Vitamin D supplementation for depression in older adults: a meta-analysis of randomized controlled trials.

In older adults, depression is associated with several other clinical problems such as cognitive impairment and low quality of life. Several studies have evaluated the relationship between vitamin D and depression in older adults; however, the results have been controversial thus far. This study aimed to investigate the effects of vitamin D supplementation on depressive symptom improvement among individuals aged ≥60 years with or without a diagnosis of depression or depressive symptoms based on a meta-analysis of randomized controlled trials (RCTs). RCTs were identified to analyze the relationship between vitamin D supplementation and depressive symptoms. MEDLINE, CENTRAL, Embase, and PsycINFO were systematically searched for relevant articles published from inception to November 2022. RCTs that evaluated the effect of vitamin D supplementation in participants aged ≥60 years compared to placebo were included. A random effects model was used in this meta-analysis because of the differences between the included RCTs. The quality of the RCTs was assessed using Risk of Bias 2. Seven trials were included in the analyses. The primary outcome of pre-post score changes included five trials with a total of 752 participants. The secondary outcome of post-intervention score included all seven trials with a total of 4,385 participants. No significant improvement in depressive symptoms in either pre-post score changes [standardized mean difference (SMD) = -0.49; 95% confidence interval (CI) -1.07-0.09; p = 0.10] or post-intervention score (SMD = -0.10; 95% CI -0.28-0.07; p = 0.25) was found. Vitamin D supplementation in older adults was not associated with an improvement in depressive symptoms. More studies in older adults are needed to evaluate the association between vitamin D supplementation and depression.

Chronic mitochondria-targeted antioxidant supplementation in older adults alters circulating factors to improve endothelial cell function

Age-related vascular endothelial dysfunction, characterized by reduced nitric oxide (NO) bioavailability, is mediated in part by excess production of mitochondrial reactive oxygen species (mtROS). Excess mtROS also oxidizes circulating lipids (i.e., low-density lipoprotein [LDL]) to promote endothelial dysfunction with aging. We recently showed that 6-weeks of treatment with the mitochondria-targeted antioxidant MitoQ (MQ) (20 mg/day) improved endothelial function in vivo in older adults. The improvements in endothelial function with MQ were mediated by reduced mtROS and associated with lower plasma levels of oxidized LDL (oxLDL). However, the complete mechanisms by which MQ improves endothelial function, and if MQ-related decreases in oxLDL are mechanistically involved, remain unknown. PURPOSE. To determine if chronic MQ supplementation-mediated changes in the circulating milieu contribute to improvements in endothelial cell (EC) function and the mechanistic role of reductions in oxLDL. METHODS. Plasma samples were obtained 24 h after the last dose from 19 older adults (mean±SEM: 67±1 yrs; 11 women) who completed our crossover design pilot trial to assess the efficacy of 6-weeks of MQ vs. placebo (PLA) treatment for improving endothelial function. Using an ex vivo model of endothelial function, acetylcholine (Ach)-stimulated NO bioavailability (DAR-4M-AM) was quantified in human aortic ECs (HAECs) following exposure to plasma collected after each phase of the study (MQ and PLA). The role of mtROS production (MitoSOX) in plasma-mediated changes in HAEC function was also assessed. To elucidate the role of lower oxLDL with MQ treatment on HAEC function, physiological levels of oxLDL were ‘added back’ to plasma collected from subjects after MQ treatment at a concentration corresponding to the average reduction after MQ (14 ng/mL). To determine if lower oxLDL with MQ treatment improves HAEC function through a reduction in binding to the oxLDL receptor LOX-1, HAECs were subjected to LOX-1 blocking antibodies prior to plasma exposure under the 3 experimental conditions (PLA; MQ; MQ + oxLDL [‘add back’]) in a subset of subjects (N=9; 67±1 yrs; 5 women). RESULTS. Ach-stimulated NO bioavailability was higher (PLA: 1.0±0.05; MQ: 1.24±0.08; P=0.0002) and mtROS was lower (PLA: 1.0±0.09; MQ: 0.76±0.08; P=0.003) in HAECs exposed to plasma collected from subjects after MQ treatment compared to PLA. Normalizing oxLDL (‘add back’) abolished the effects of MitoQ treatment. LOX-1 blockade modulated Ach-stimulated NO and mtROS production to levels comparable to (P&gt;0.98) or lower than (P&lt;0.047) MQ in all 3 groups, respectively. CONCLUSIONS. Chronic MQ supplementation in older adults alters circulating factors by decreasing plasma oxLDL to reduce oxLDL-LOX-1 signaling-mediated mtROS production and improve EC function. These findings extend insight into the mechanisms by which mitochondria-targeted antioxidant treatment improves endothelial function with aging. 1R21AG049451-01A1 (DRS); 5T32DK007135-46 (KOM); K01DK115524-01A1 (MJR) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The effect of resveratrol supplementation on biomarkers of liver health: A systematic review and meta-analysis of randomized controlled trials.

This study aimed to evaluate the effect of resveratrol on liver biomarkers in adult participants, using systematic review and meta-analysis of randomized controlled trials. PubMed, Scopus, Web of Science and Cochran Library was searched, up to October 2021. The pooled effects were calculated using a random-effects model and expressed as weighted mean difference and 95% confidence interval. The methodological quality of studies as well as certainty of evidence were assessed by standard tools. Thirty-seven relevant trials were found. Although overall analysis found no significant change, subgroup analysis showed a significant improvement in alanine aminotransferase (ALT; -7.79 U/L) and glutamyl transferase (-6.0U/L) in patients with liver disorders, and ALT (-2.22 U/L) in younger adults; however, high-dose supplementation (>1,000 mg/day) appeared to increase alkaline phosphatase concentration (+5.07 U/L). ALT also increased in older adults (+2.33 U/L) following resveratrol supplementation. We found resveratrol did not have a significant effect on liver health in the general population. However, resveratrol could be effective in patients with liver disorders. Our findings also suggest that high-dose resveratrol administration and supplementation in older adults should be performed with caution. Further high-quality clinical trials are also needed to firmly establish the clinical efficacy of resveratrol.

Exercise and Protein Supplementation Recommendations for Older Adults With Sarcopenic Obesity: A Meta-Review.

This systematic meta-review evaluated the effects of exercise with and without protein interventions on muscle strength and function in older adults with sarcopenic obesity. PubMed, Cochrane Database of Systematic Reviews, Cumulative Index to Nursing and Allied Health Literature, Scopus, and SPORTDiscus databases were searched through February 2021 for relevant systematic reviews and meta-analyses with aerobic, resistance, and/or combined training interventions with and without protein supplementation in older adults ≥ 65years with sarcopenic obesity. This meta-review showed that exercise with and without protein supplementation improved body composition (i.e.,decreased percentage body fat) and functional outcomes (i.e.,gait speed and grip strength). Because the current literature is limited, determining the effects of exercise and combined protein supplementation in this population requires further investigation. In the meantime, protein recommendations should align with general sarcopenia recommendations. Based upon available findings, tentative exercise recommendations to optimize health outcomes in this population are proposed.

Editorial introductions.

Editorial introductions.

Medium‐chain fatty acids in combination with a multidomain lifestyle intervention in Alzheimer’s disease prevention: Protocol design to study implementation

AbstractBackgroundAlzheimer’s disease (AD) neuropathology begins 20 to 30 years before clinical diagnosis. Thus, there is an opportunity to implement strategies to prevent the progression of AD. Insulin resistance in the brain causes a disruption in glucose utilisation. Medium‐chain fatty acids (MCFA) are readily available substrates for the synthesis of ketone bodies (KB), which are an alternative brain fuel not controlled by insulin. A constant supply of KB may close the energy gap in the AD‐prone brain, and in doing so prevent or delay symptom onset, or protect the brain from further degeneration. There is increasing evidence that multidomain lifestyle interventions with dietary components significantly impact cognitive decline. Yet, these interventions have not considered the effects MCFA supplementation, to ensure sufficient energy for the brain.MethodThis is a phase II placebo‐controlled, randomised double‐blind 24‐month intervention trial of MCFA supplementation within the AUstralian‐multidomain Approach to Reduce dementia Risk by prOtecting brain health With lifestyle intervention (AU‐ARROW) study, to investigate the additive effect of MCFA supplementation in older adults at increased risk of AD. A total of 124 participants will be recruited aged 60‐79 years, with subjective cognitive decline. Participants will be randomised 1:1 into either the intervention or placebo groups and will consume 3 daily doses at 15mL per dose of either MCFA or placebo supplement whilst continuing the AU‐ARROW protocol, which includes dietary education, physical activity, brain training, and health education.ResultThe primary outcomes involve statistical assessment of cognition, blood ketone body levels, and brain glucose utilisation. At baseline, and every 6 months, participants will have fasting blood samples collected. At baseline, 12, and 24 months, participants will undergo cognitive assessments. At baseline and 24 months, participants will undergo fluorodeoxyglucose positron emission tomography scans to determine brain glucose utilisation.ConclusionThe final protocol is expected to maximise data collection and analyses. Combined with AU‐ARROW, it will allow for a) the implementation of MCFA supplementation guidelines in a plan to reduce cognitive decline and risk of AD, b) the determination of effects of MCFA consumption on neuroimaging and blood‐based biomarkers, and c) the comparison of between subject differences.

Factors influencing thirst perception during the consumption of oral nutritional supplements in older adults

Oral Nutritional Supplements (ONS) are often used as a strategy to aid nutrient adequacy in older adults. Research has highlighted that thirst increases with ONS consumption. This, combined with older adults’ tendency for diminished thirst, may contribute to reduced ONS adherence. This study investigated how alterations in viscosity, protein content, and sweetness of ONS impact thirst perception after ONS consumption.Seventy-two older adults (mean age 71 ± 4 years, 27 men, 45 women) evaluated four ONS of varying protein contents, four ONS of varying sweetness, and four ONS of varying viscosities over three days, one day per ONS set. Each ONS was consumed over three sips (10 mL each). After three sips the panellists recorded their thirst, mouth-dryness, ‘prospective water consumption’, appetite (Visual Analogue Scales), and liking (9-point hedonic scale). Salivary flow was recorded at the start of each visit. ONS osmolality was also measured.Most panellists had diminished thirst and low salivary flow. Each ONS was hypertonic and those highest in protein had significantly higher osmolality. Thirst, mouth-drying, and ‘prospective water consumption’ were not significantly different following consumption of different ONS. Significant differences between cohort subgroups were observed. Non-denture wearers had higher ratings for ‘prospective water consumption’ compared to denture wearers. Those who needed regular reminders to drink water were significantly thirstier and had higher ratings for mouth-drying and ‘prospective water consumption’ than those who do not. Female panellists had lower liking for ONS, than males.

Effects of leucine-rich protein supplements in older adults with sarcopenia: A systematic review and meta-analysis of randomized controlled trials

ObjectivesThis study examined whether leucine-rich protein supplements improve muscle strength, mass, and performance in sarcopenic older adults. MethodsWe searched PubMed-Medline, Embase, and Cochrane Library databases for randomized controlled trials comparing leucine-rich protein supplements with a control intervention in sarcopenic older adults. A pairwise meta-analysis using a fixed-effects model was performed. The primary outcome of interest was muscle strength regardless of the measures used. Effect sizes were computed as standardized mean differences (SMDs) with 95% confidence intervals (CIs). ResultsSix randomized controlled trials including a total of 699 participants were retrieved. Leucine-rich protein supplements improved participants’ overall muscle strength, mass, and performance compared to the control group (SMD = 0.939; 95% CI, 0.440–1.438; P < 0.001). As the primary outcome, muscle strength improved significantly in the leucine group (SMD = 0.794; 95% CI, 0.104–1.485; P = 0.024). ConclusionLeucine-rich protein supplements improve muscle strength in sarcopenic older adults. They may be suggested in nutritional treatment of sarcopenia.

High-dose versus standard-dose vitamin D supplementation in older adults with COVID-19 (COVIT-TRIAL): A multicenter, open-label, randomized controlled superiority trial.

BackgroundVitamin D supplementation has been proposed as a treatment for Coronavirus Disease 2019 (COVID-19) based on experimental data and data from small and uncontrolled observational studies. The COvid19 and VITamin d TRIAL (COVIT-TRIAL) study was conducted to test whether a single oral high dose of cholecalciferol (vitamin D3) administered within 72 hours after the diagnosis of COVID-19 improves, compared to standard-dose cholecalciferol, the 14-day overall survival among at-risk older adults infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).Methods and findingsThis multicenter, randomized, controlled, open-label, superiority trial involved collaboration of 9 medical centers in France. Patients admitted to the hospital units or living in nursing homes adjacent to the investigator centers were eligible if they were ≥65 years, had SARS-CoV-2 infection of less than 3 days, and at least 1 COVID-19 worsening risk factor (among age ≥75 years, SpO2 ≤94%, or PaO2/FiO2 ≤300 mm Hg). Main noninclusion criteria were organ failure requiring ICU, SpO2 ≤92% despite 5 L/min oxygen, life expectancy <3 months, vitamin D supplementation >800 IU/day during the preceding month, and contraindications to vitamin D supplements. Eligible and consenting patients were randomly allocated to either a single oral high-dose (400,000 IU) or standard-dose (50,000 IU) cholecalciferol administered under medical supervision within 72 hours after the diagnosis of COVID-19. Participants and local study staff were not masked to the allocated treatment, but the Steering Committee and the Data and Safety Monitoring Board were masked to the randomization group and outcome data during the trial. The primary outcome was 14-day overall mortality. Between April 15 and December 17, 2020, of 1,207 patients who were assessed for eligibility in the COVIT-TRIAL study, 254 met eligibility criteria and formed the intention-to-treat population. The median age was 88 (IQR, 82 to 92) years, and 148 patients (58%) were women. Overall, 8 (6%) of 127 patients allocated to high-dose cholecalciferol, and 14 (11%) of 127 patients allocated to standard-dose cholecalciferol died within 14 days (adjusted hazard ratio = 0.39 [95% confidence interval [CI], 0.16 to 0.99], P = 0.049, after controlling for randomization strata [i.e., age, oxygen requirement, hospitalization, use of antibiotics, anti-infective drugs, and/or corticosteroids] and baseline imbalances in important prognostic factors [i.e., sex, ongoing cancers, profuse diarrhea, and delirium at baseline]). The number needed to treat for one person to benefit (NNTB) was 21 [NNTB 9 to ∞ to number needed to treat for one person to harm (NNTH) 46]. Apparent benefits were also found on 14-day mortality due to COVID-19 (7 (6%) deaths in high-dose group and 14 (11%) deaths in standard-dose group; adjusted hazard ratio = 0.33 [95% CI, 0.12 to 0.86], P = 0.02). The protective effect of the single oral high-dose administration was not sustained at 28 days (19 (15%) deaths in high-dose group and 21 (17%) deaths in standard-dose group; adjusted hazard ratio = 0.70 [95% CI, 0.36 to 1.36], P = 0.29). High-dose cholecalciferol did not result in more frequent adverse effects compared to the standard dose. The open-label design and limited study power are the main limitations of the study.ConclusionsIn this randomized controlled trial (RCT), we observed that the early administration of high-dose versus standard-dose vitamin D3 to at-risk older patients with COVID-19 improved overall mortality at day 14. The effect was no longer observed after 28 days.Trial registrationClinicalTrials.gov NCT04344041.

Cost-effectiveness of vitamin D3 supplementation in older adults with vitamin D deficiency in Ireland

BackgroundThis study investigated the cost-effectiveness of vitamin D3 supplementation in older adults in Ireland, with year-round vitamin D deficiency (serum 25-hydroxyvitamin D concentration <30 nmol/L) (13% of Irish adults), from...