By Austin Ulrich, PharmD, BCACP
Consultant Pharmacist, Greensboro, NC
SYNOPSIS: Data from a large, randomized trial that included 25,871 adults age 50 years or older indicated 2,000 daily units of vitamin D3 and 1 g daily of omega-3 fatty acid supplementation did not affect frailty.
SOURCE: Orkaby AR, Dushkes R, Ward R, et al. Effect of vitamin D3 and omega-3 fatty acid supplementation on risk of frailty: An ancillary study of a randomized clinical trial. JAMA Netw Open 2022;5:e2231206.
With an increasingly aging U.S. population, frailty is becoming a more urgent concern for many patients and healthcare practitioners. Frailty is defined as “a state of increased vulnerability to poor resolution of homeostasis following a stress.”1 It leads to several adverse health outcomes, including falls, disability, and delirium.1 Frailty is age-related, becoming more common as individuals age, with an estimated 25% to 50% of people older than age 85 years living with frailty. This condition tends to be associated with genetic and environmental factors that promote cumulative molecular and cellular damage. This leads to deteriorated physiologic reserve in multiple organ systems. Depending on individual physical activity levels and nutritional factors, the depleted physiologic reserve in these organ systems can cause frailty.1
Researchers theorized anti-inflammatory compounds, such as vitamin D3 and omega-3 fatty acids, could modify the trajectory of frailty.2 Certain deficiencies may contribute to frailty. For example, low levels of serum 25-hydroxyvitamin D are associated with frailty, possibly as a manifestation of suboptimal nutrition or direct effects on bone and muscle health.3
In a prespecified ancillary to the Vitamin D and Omega-3 (VITAL) trial, Orkaby et al tested the hypothesis that vitamin D3 and omega-3 fatty acid supplements would lower the risk of frailty. The authors of the VITAL trial enrolled community-dwelling adults, men age ≥ 50 years, and women age ≥ 55 years without cardiovascular disease (CVD) or cancer.4,5 Researchers recruited 25,871 patients in the United States from November 2011 to March 2014 and followed them through Dec. 31, 2017. Patients were randomized using a 2 × 2 factorial method to 2,000 units vitamin D3 daily and 1 g omega-3 fatty acids daily. The original purpose of the VITAL trial was to evaluate the effects of vitamin D3 and omega-3 fatty acid supplementation on CVD and cancer. However, in this analysis (conducted from Dec. 1, 2019, to March 30, 2022, Orkaby et al used the data to characterize patients’ condition according to the validated Rockwood frailty index (FI).6
In this frailty analysis, there were enough data on 25,057 patients to calculate an FI. Mean age at baseline was 67.2 years, and about half the cohort was women. The mean FI score was 0.109, and 12.7% of patients met criteria for frailty at baseline. After a median follow-up of five years, frailty scores increased to a mean of 0.121. The authors observed no significant changes in frailty score by vitamin D3 and omega-3 fatty acid supplementation status compared to placebo (-0.0002; P = 0.85 and -0.0001; P = 0.90, respectively). Similarly, investigators saw no changes with respect to the rate of change in mean frailty score and incident frailty. The authors concluded treatment with vitamin D3 or omega-3 fatty acids did not affect the rate of frailty change or incidence over time. These results do not support routine supplementation for frailty prevention in generally healthy community-dwelling older adults.
COMMENTARY
To date, no studies of the effects of dietary supplements on frailty have demonstrated benefit.7 The work by Orkaby et al is no exception, despite the large population size and rigorous study design. One limitation of the VITAL population is participants likely were healthier than the general population, highlighted by the lower rates of frailty observed in the study sample. In contrast to dietary supplements, the Mediterranean diet has demonstrated a reduction in frailty incidence for patients who are adherent.8 Although not demonstrated to reduce frailty risk, exercise is another widely recommended lifestyle intervention for older adults to improve overall health. Clinicians should continue to emphasize regular exercise for their patients, especially older adults. Clinicians also should consider encouraging older adults to follow the Mediterranean diet, particularly those at risk for frailty.
REFERENCES
1. Clegg A, Young J, Iliffe S, et al. Frailty in elderly people. Lancet 2013;381:752-762.
2. Vellas B, Sourdet S. Prevention of frailty in aging. J Frailty Aging 2017;6:174-177.
3. Artaza-Artabe I, Sáez-López P, Sánchez-Hernández N, et al. The relationship between nutrition and frailty: Effects of protein intake, nutritional supplementation, vitamin D and exercise on muscle metabolism in the elderly. A systematic review. Maturitas 2016;93:89-99.
4. Manson JE, Cook NR, Lee IM, et al. Marine n-3 fatty acids and prevention of cardiovascular disease and cancer. N Engl J Med 2019;380:23-32.
5. Manson JE, Cook NR, Lee IM, et al. Vitamin D supplements and prevention of cancer and cardiovascular disease. N Engl J Med 2019;380:33-44.
6. Searle SD, Mitnitski A, Gahbauer EA, et al. A standard procedure for creating a frailty index. BMC Geriatr 2008;8:24.
7. Eckstrom E, De Lima B. There is no magic pill to prevent frailty — You still have to eat your vegetables. JAMA Netw Open 2022;5:e2231147.
8. Kojima G, Avgerinou C, Iliffe S, Walters K. Adherence to Mediterranean diet reduces incident frailty risk: Systematic review and meta-analysis. J Am Geriatr Soc 2018;66:783-788.
Data from a large, randomized trial that included 25,871 adults age 50 years or older indicated 2,000 daily units of vitamin D3 and 1 g daily of omega-3 fatty acid supplementation did not affect frailty.
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