Effect of Vitamin D Supplementation, Omega-3 Fatty Acid Supplementation, or a Strength-Training Exercise Program on Clinical Outcomes in Older Adults

Bischoff‐Ferrari, Heike A.; Vellas, Bruno; Rizzoli, René; Kressig, Reto W.; Silva, José António Pereira da; Blauth, M.; Felson, David T.; McCloskey, Eugène; Watzl, Bernhard; Hofbauer, Lorenz C.; Felsenberg, Dieter; Willett, Walter C.; Dawson‐Hughes, Bess; Manson, JoAnn E.; Siebert, Uwe; Theiler, Robert; Staehelin, Hannes B.; Molino, Caroline de Godoi Rezende Costa; Chocano-Bedoya, Patricia; Abderhalden, Lauren A; Egli, Andreas; Kanis, John А.; Orav, E. John

doi:10.1001/jama.2020.16909

Cited by 201 publications

(218 citation statements)

References 47 publications

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“…There was also no beneficial effect from vitamin D seen in relation to specific CVDs, including heart failure in the main ViDA study, (39) in an ancillary study to the VITAL trial, (48) and in relation to blood pressure in the DO-HEALTH study. (41) The latter result is consistent with an individual patient data meta-analysis. (49) The effect of vitamin D on arterial function, a risk factor for CVD, (50) has been studied in the ViDA study.…”

Section: Baseline Characteristicssupporting

confidence: 84%

“…The number of participants with severe vitamin D deficiency [25(OH)D <25 nmol/L] in each study was only 32 (1%) in the CAPS, 161 (3%) in the ViDA, 486 (2%) in the VITAL, and 153 (7%) in the DO‐HEALTH studies, whereas insufficiency (25(OH)D <50 nmol/L), respectively, was 248 (11%), 1534 (30%), 3625 (14%), and 841 (39%). These numbers were estimated from published data for the CAPS, (33 ) VITAL, (40 ) and DO‐HEALTH studies, (41 ) and the actual number for observed 25(OH)D in the ViDA trial. ( 39 ) The mean increase in 25(OH)D during follow‐up in the vitamin D group was 69 nmol/L in the ViDA study—more than twice as high as in the other three studies.…”

Section: Published Resultsmentioning

confidence: 99%

“…To date, only four studies have published results: CAPS, ViDA, VITAL, and DO-HEALTH. Table 2 summarizes some key baseline characteristics for the CAPS, (33) ViDA, (39) VITAL, (40) and DO-Health (41) studies, along with results for both primary and secondary outcomes and from ancillary studies to the ViDA and VITAL trials.…”

Section: Recent Mega Trials Of Vitamin D Supplementationmentioning

confidence: 99%

“…Other current mega trials-CAPS, DO-HEALTH, TIPS-3, and D-Health-have falls as a secondary outcome (Supplemental Table S1), whereas the DO-HEALTH study has recently reported that vitamin D does not improve the Short Physical Performance Battery score. (41) Further publications from these studies should provide final clarity about whether vitamin D helps to prevent falls by community-living people and to reduce the rate of falls by people living in care homes. (57) The ViDA study is the only recent mega trial to report on fractures as an outcome.…”

Section: Musculoskeletal and Mental Functionmentioning

confidence: 99%

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Is There Proof of Extraskeletal Benefits From Vitamin D Supplementation From Recent Mega Trials of Vitamin D?

Scragg

Sluyter

2021

JBMR Plus

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Scientific interest in possible extraskeletal effects of vitamin D first appeared in the 1930s soon after the structure of vitamin D was characterized, and increased in the 1980s with the development of assays of 25-hydroxyvitamin D status as a marker of vitamin D status, which in observational epidemiological studies was shown to be inversely associated with many nonskeletal diseases. This resulted in the start of seven large randomized controlled trials (n > 2000 participants in each) of vitamin D supplementation giving higher doses than previously used. The intervention periods in these trials collectively started in 2009 and continued to 2020. They have recruited participants, mostly of both sexes and over the age of 50 years, from many countries and have given either daily or monthly doses of vitamin D. Collectively, the trials have a wide range of outcomes with the main focus on the prevention of cancer, cardiovascular disease, and fractures, besides many other outcomes. The findings of four trials have been published, and they have shown that vitamin D supplementation does not prevent hard-disease endpoints, such as cardiovascular disease, cancer, fractures, or falls, aside from a possible beneficial effect against cancer mortality. In contrast, beneficial effects were seen for intermediate outcomes such as BMD of spine and hips, arterial function, and lung function, especially in people with vitamin D deficiency. The finding of a benefit primarily in people with vitamin D deficiency, if confirmed by the other trials, would support a population approach to preventing vitamin D deficiency using fortification rather than the high-risk approach of screening for deficiency combined with supplementation. The findings on other outcomes from the three published trials, along with the findings from the four unpublished trials, are expected within the next 2 to 3 years to clarify the role of vitamin D supplementation in preventing nonskeletal disease.

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Section: Baseline Characteristicssupporting

confidence: 84%

Section: Published Resultsmentioning

confidence: 99%

Section: Recent Mega Trials Of Vitamin D Supplementationmentioning

confidence: 99%

Section: Musculoskeletal and Mental Functionmentioning

confidence: 99%

See 2 more Smart Citations

Is There Proof of Extraskeletal Benefits From Vitamin D Supplementation From Recent Mega Trials of Vitamin D?

Scragg

Sluyter

2021

JBMR Plus

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“…On the other hand, the recent STRENGTH (Statin Residual Risk Reduction with Epanova in High CV Risk Patients with Hypertriglyceridemia) trial, evaluating the effect of Epanova ® 4 g daily compared to placebo (corn oil) on reducing the risk of major adverse cardiovascular events in 13,086 patients on optimal statin therapy with mixed dyslipidemia and at high risk for CV disease, was stopped early due to its low likelihood of demonstrating a benefit [ 104 ]. Finally, an RCT of krill oil, i.e., omega 3 mostly as phospholipids, carried out in 242 patients with severe hypertriglyceridemia, was also stopped after 12 of the programmed 46 weeks because of a strong placebo effect and the very recent Bischoff et al publication reported no significant differences in improvement in systolic and diastolic blood pressure of older adults given 1 g/d of algal oil (330 mg of EPA and 660 mg DHA) [ 105 ]. Finally, a very recent trial of 930 mg/d EPA and 660 mg/d DHA vs. corn oil given to elderly patients failed to prove benefits [ 106 ].…”

Section: Dietary Fats: Why We Need Them?mentioning

confidence: 99%

Fatty Acids and Cardiovascular Risk. Evidence, Lack of Evidence, and Diligence

Visioli

Poli²

2020

Nutrients

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One of the most controversial areas of nutrition research relates to fats, particularly essential fatty acids, in the context of cardiovascular disease risk. A critical feature of dietary fatty acids is that they incorporate into the plasma membrane, modifying fluidity and key physiological functions. Importantly, they can reshape the bioavailability of eicosanoids and other lipid mediators, which direct cellular responses to external stimuli, such as inflammation and chronic stress conditions. This paper provides an overview of the most recent evidence, as well as historical controversies, linking fat consumption with human health and disease. We underscore current pitfalls in the area of fatty acid research and critically frame fatty acid intake in the larger context of diet and behavior. We conclude that fundamental research on fatty acids and lipids is appropriate in certain areas, but the rigor and reproducibility are lacking in others. The pros and cons are highlighted throughout the review, seeking to guide future research on the important area of nutrition, fat intake, and cardiovascular disease risk.

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Vitamin D₃ to Treat COVID-19

Leaf

Ginde

2021

JAMA

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Biological activity of vitamin D and its metabolites include, among other properties, potent antimicrobial and antiinflammatory effects in vitro. 1 In animal models, administration of vitamin D metabolites attenuates a variety of acute organ dysfunction, including acute lung injury. 2 Observational data from patient cohorts support the potential therapeutic application of these findings. 3 Specifically, lower circulating levels of vitamin D metabolites are independently associated with worse outcomes in patients with acute illness, including patients with coronavirus disease 2019 (COVID-19). 4 These multiple lines of evidence in support of a potential therapeutic role for vitamin D generated enthusiasm over the past decade for testing whether administration of large doses of vitamin D might improve outcomes in various groups of patients, including those with critical illness. The Correction of Vitamin D Deficiency in Critically Ill Patients (VITdAL-ICU) study was a multicenter randomized clinical trial that tested the effect of vitamin D 3 administration (540 000 IU) vs placebo in 475 critically ill patients with vitamin D deficiency, defined as 25-hydroxyvitamin D (25[OH]D) less than or equal to 20 ng/mL. The primary end point, hospital length of stay, was similar between the groups, although hospital mortality (a secondary end point) was lower in patients who received vitamin D 3 vs placebo among those with severe vitamin D deficiency (defined as 25[OH]D ≤12 ng/mL). 5 The Vitamin D to Improve Outcomes by Leveraging Early Treatment (VIOLET) trial sought to examine the effect of the same dose of vitamin D 3 (540 000 IU) vs placebo on 90-day mortality in 3000 critically ill patients with vitamin D deficiency, but was stopped early for futility after enrollment of 1360 patients demonstrated very low likelihood for benefit. 6 Randomized clinical trials testing vitamin D 3 administration as a therapeutic strategy for disease prevention in other settings have yielded similarly null results. 7-9 The COVID-19 pandemic has spurred renewed interest in vitamin D to address viral replication and hyperinflammation that have a major role in the pathogenesis of severe COVID-19. In addition to known antimicrobial and anti-inflammatory effects, vitamin D metabolites also have direct action on angiotensin-converting enzyme 2 (ACE2), which serves as the cell surface entry receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Vitamin D metabolites upregulate ACE2 expression in pulmonary microvascular endothelial cells in animal models of acute lung injury. 10 Although enhanced expression of ACE2 could theoretically increase viral entry into cells, it may paradoxically have ben

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Effect of Vitamin D Supplementation, Omega-3 Fatty Acid Supplementation, or a Strength-Training Exercise Program on Clinical Outcomes in Older Adults

Cited by 201 publications

References 47 publications

Is There Proof of Extraskeletal Benefits From Vitamin D Supplementation From Recent Mega Trials of Vitamin D?

Is There Proof of Extraskeletal Benefits From Vitamin D Supplementation From Recent Mega Trials of Vitamin D?

Fatty Acids and Cardiovascular Risk. Evidence, Lack of Evidence, and Diligence

Vitamin D₃ to Treat COVID-19

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Effect of Vitamin D Supplementation, Omega-3 Fatty Acid Supplementation, or a Strength-Training Exercise Program on Clinical Outcomes in Older Adults

Cited by 201 publications

References 47 publications

Is There Proof of Extraskeletal Benefits From Vitamin D Supplementation From Recent Mega Trials of Vitamin D?

Is There Proof of Extraskeletal Benefits From Vitamin D Supplementation From Recent Mega Trials of Vitamin D?

Fatty Acids and Cardiovascular Risk. Evidence, Lack of Evidence, and Diligence

Vitamin D3 to Treat COVID-19

Contact Info

Product

Resources

About

Vitamin D₃ to Treat COVID-19