April 5, 2023

Preventing Frailty in Elders

Can vitamin D, essential fats, and exercise lower risk?
While single interventions may have little effect, stacking interventions may yield more benefits.


Gagesch M, Wieczorek M, Vellas B, et al. Effects of vitamin D, omega-3 fatty acids and a home exercise program on prevention of pre-frailty in older adults: the DO-HEALTH randomized clinical trial. J Frailty Aging. 2023;12(1):71-77.

Study Objective

To determine if, over a 3-year period, vitamin D3, omega-3 fatty acids, and a simple home exercise program, alone or in combination, contribute to prefrailty and frailty in robust older adults.

Key Takeaway

In generally healthy and active older adults without major comorbidities, a combination of supplemental vitamin D3, marine omega-3s, and a simple home exercise program may help to reduce the risk of developing prefrailty.


Multicenter, randomized, double-blind, placebo-controlled trial


The study included 1,137 adults, robust at baseline; 56.5% were women, mean age was 74.3 (±4.0) years, mean body mass index (BMI) was 26.1 kg/m2 (±4.0), and 432 (38%) were living alone. Participants reported a mean physical activity volume of 40.3 (±32.9) metabolic equivalent of task–hours (MET-hrs) per week and a mean physical performance score of 11.3 points (±1.1) on the short physical performance battery (SPPB; score range: minimum 0; maximum 12 points). 


In total, there were 8 different groups (2x2x2 factorial design): 

  1. Vitamin D3 (2,000 IU/d) + omega-3 fatty acids (1 g/d) + simple home exercise program (SHEP)
  2. Vitamin D3 (2,000 IU/d) + omega-3 fatty acids (1 g/d) + sham exercises
  3. Vitamin D3 (2,000 IU/d) + placebo oil + SHEP
  4. Vitamin D3 (2,000 IU/d) + placebo oil + sham exercises
  5. Placebo vitamin D3 + omega-3 fatty acids (1 g/d) + SHEP
  6. Placebo vitamin D3 + omega-3 fatty acids (1 g/d) + sham exercises
  7. Placebo vitamin D3 + placebo oil + SHEP
  8. Control

All supplements were administered orally once per day, and the duration of the intervention was 3 years. Vitamin D was in the form of D3 stabilized with dl-alpha-tocopherol, 2.5 pro mill. Omega-3 fatty acids were in a 1:2 ratio of eicosapentaenoic acid (EPA) to docosahexaenoic acid (DHA). The study does not mention the placebo for vitamin D3. The placebo for omega-3 fatty acids was a capsule filled with sunflower oil. The sham exercises were stretching exercises that did not provide a training effect. SHEP was unsupervised training for 30 minutes 3 times per week. 

Study Parameters Assessed

Frailty and prefrailty status were operationalized using the 5 domains of the Fried physical frailty phenotype assessment. Grip strength, subjective fatigue affecting quality of life, involuntary weight loss greater than 4.5 kg or 5% of body weight in 1 year, low gait speed less than or equal to 0.65 m/s, and low activity level constituted the 5 domains. 

Primary Outcome Assessed

Incidence of frailty and prefrailty

Key Findings

The key findings were odds ratios of categorization between robust health and prefrailty. Odds ratios (OR, 95% CI) of becoming prefrail over the 3-year follow-up comparing the individual treatment effects were:

  • 0.81 (0.62–1.07; P=0.13) for receiving vitamin D3 vs no vitamin D3
  • 0.84 (0.64–1.11; P=0.22) for receiving omega-3s vs no omega-3s
  • 0.89 (0.67–1.16; P=0.38) for receiving SHEP vs no SHEP

For the combined treatment effects, the odds ratios (OR, 95% CI) of becoming prefrail over the 3-year follow-up were:

  • 0.69 (0.46–1.01; P=0.06) for receiving vitamin D3 plus omega-3s vs no vitamin D3 and omega-3s
  • 0.75 (0.51–1.10; P=0.14) for receiving omega-3s plus SHEP vs no omega-3s and SHEP
  • 0.72 (0.49–1.06; P=0.10) for receiving vitamin D3 plus SHEP vs no vitamin D3 and SHEP
  • 0.61 (0.38–0.98; P=0.04) for receiving all 3 treatments combined vs placebo


The DO-HEALTH study was funded by the Seventh Framework Program of the European Commission (grant agreement 278588), the University of Zurich (Chair for Geriatric Medicine and Aging Research), DSM Nutritional Products, Roche, NESTEC, Pfizer, and Streuli. Open Access funding was provided by University Zurich. The authors declare no conflicts of interest.

Practice Implications & Limitations

Increased attention is being placed on simple and accessible lifestyle modifications that contribute to health outcomes consistent with vibrant humans. This awareness is helmed by the emerging field of circadian biology, which often reminds us that modern human existence contrasts starkly with the conditions of our ancestors that shaped our bodies and minds. This includes concepts that better align to our hardwired predispositions, with the goal of promoting health and happiness throughout life, including older age. Recommendations, such as consistently getting good-quality sleep,1 spending time in nature,2 receiving morning sunlight exposure,3 eating nutrient-dense whole foods,4 investing time each day to move the body,5 and reducing screen time6 are quickly becoming practices many are working into their daily and weekly routines.

Interestingly, as with numerous realities of the human experience, an individual’s ability to respond to stimuli may be strongest while young. In its youth, the body easily responds to normal dietary glucose;7 vision is the rule rather than the exception;8 feet rarely hurt outside of injury.9 As bodies age, resilience to some common experiences deteriorates. Wounds may become chronic or take longer to heal;10 challenges are associated with both gaining and losing weight;11 movement may be limited due to pain and concern around falls;12 acquiring, preparing, and consuming healthy food can be challenging.13 Insofar as anyone is able to influence decline, there are choices to make and suggestions we can give patients that limit the slide into frailty and preserve health span longer into the future. 

This study was likely underpowered to detect any effect of exercise, as there was likely little difference in the actual amount of exercise done by the intervention vs the placebo groups.

Choosing these protocols based on research can be challenging as many of these areas are limited by the time, duration, power, and quality of the existing body of research, and yet healthcare providers are looking for ways to help patients stave off prefrailty and, later, frailty, as long as possible.

This study examined whether taking vitamin D and omega-3 fatty acids and participating in a home-exercise program could help prevent prefrailty and frailty in older adults. The study included 1,137 people who were healthy and not frail at the beginning of the study. Over 3 years, 61% of these people became prefrail, but the study found that vitamin D, omega-3 fatty acids, and the home-exercise program by themselves did not statistically significantly reduce the risk of becoming prefrail. However, when all 3 treatments were combined, there was a lower risk of becoming prefrail compared to taking a placebo. Only 2.6% of people in the study became frail; thus, the study did not have enough power to show if the treatments were effective in preventing frailty, as the authors note. 

Overall, the study suggests that a combination of vitamin D, omega-3 fatty acids, and home exercise may help prevent prefrailty in older adults. The authors discussed adherence to the assigned study protocol in a prior publication. They found that adherence was less than ideal, particularly for the exercise group, with only 61.8% of participants reporting having performed the unsupervised exercise routine 3 or more times per week. Given that participants in the intervention arm may have over-reported their adherence to the regime and that placebo participants had a moderate-to-high level of activity at baseline, this study was likely underpowered to detect any effect of exercise, as there was likely little difference in the actual amount of exercise done by the intervention vs the placebo groups. 

The strongest practice implications may be that the protocols were not personalized or adapted to the individual, which is excellent for research but of less application in clinical practice. Of interest is that vitamin D alone did not reduce the risk of prefrailty status. Neither did movement or omega-3 fatty acid consumption. However, the combination did have statistically significant effects. In clinical practice, vitamin D may be dosed to reach a therapeutic target level of sufficiency or optimal levels. Omega-3 fatty acid intervention may be supplemented to a therapeutic target level, but they’re more commonly recommended at dosages consistent with the conditions that the individual patient may have. As an example, the recommendation for individuals with hypertriglyceridemia might be 4 grams EPA+DHA.14 Finally, 30 minutes of exercise 3 times per week is well below the 150 minutes of moderate-intensity activity per week recommended by the Centers for Disease Control and Prevention. Outside of personalizing recommendations, healthcare practitioners may rely on this research to help educate patients that single interventions are not always optimal and stacking interventions may be more useful to improve health span and reduce prefrailty status.

Based on this research, healthcare providers should encourage patients to enjoy sunlight safely, eat fatty fish (eg, sardines, mackerel, anchovies, salmon, herring), and engage in movement that is comfortable to the body, as these practices may offer benefits. Our bodies can safely manufacture vitamin D endogenously in meaningful amounts by spending time outside with skin exposed to the sun;15 omega-3s are commonly consumed, often from fish, as part of a healthy diet; everyday light movement, similar to what our ancestors may have engaged in (eg, gardening, doing household chores) benefits the body and mind.16,17 When diet and lifestyle cannot suffice, adding a supplementation and exercise program similar to this study may offer benefits. 

Categorized Under


  1. Ramar K, Malhotra RK, Carden KA, et al. Sleep is essential to health: an American Academy of Sleep Medicine position statement. J Clin Sleep Med. 2021;17(10).
  2. White MP, Alcock I, Grellier J, et al. Spending at least 120 minutes a week in nature is associated with good health and wellbeing. Sci Rep. 2019;9(1).7730
  3. National Institute of General Medical Sciences. Circadian rhythms. National Institute of General Medical Sciences website. https://nigms.nih.gov/education/fact-sheets/Pages/Circadian-Rhythms.aspx. Accessed March 28, 2023.
  4. Elizabeth L, Machado P, Zinöcker M, Baker P, Lawrence M. Ultra-processed foods and health outcomes: a narrative review. Nutrients. 2020;12(7):1955.
  5. Szychowska A, Drygas W. Physical activity as a determinant of successful aging: a narrative review article. Aging Clin Exp Res. 2022;34(6)1209-1214.
  6. Pedersen J, Rasmussen MGB, Sørensen SO, et al. Effects of limiting digital screen use on well-being, mood, and biomarkers of stress in adults. npj Mental Health Res. 2022;1(14):1-10.
  7. Shou J, Chen PJ, Xiao WH. Mechanism of increased risk of insulin resistance in aging skeletal muscle. Diabetol Metab Syndr. 2020;12:14.
  8. Magnus E, Vik K. Older adults recently diagnosed with age-related vision loss: readjusting to everyday life. Act Adapt Aging. 2016;40(4):296-319.
  9. Menz HB, Dufour AB, Casey VA, et al. Foot pain and mobility limitations in older adults: the Framingham Foot Study. J Gerontol A Biol Sci Med Sci. 2013;68(10):1281-1285.
  10. Alam W, Hasson J, Reed M. Clinical approach to chronic wound management in older adults. J Am Geriatr Soc. 2021;69(8):2327-2334.
  11. Coker RH, Wolfe RR. Weight loss strategies in the elderly: a clinical conundrum. Obesity. 2017;26(1):22-28.
  12. Hicks C, Levinger P, Menant JC, et al. Reduced strength, poor balance and concern about falls mediate the relationship between knee pain and fall risk in older people. BMC Geriatr. 2020;20(1):94.
  13. Robinson SM. Improving nutrition to support healthy ageing: what are the opportunities for intervention? Proc Nutr Soc. 2017;77(3):257-264.
  14. Skulas-Ray AC, Wilson PWF, Harris WS, et al. Omega-3 fatty acids for the management of hypertriglyceridemia: a science advisory from the American Heart Association. Circulation. 2019;140(12):e673-e691.
  15. Alfredsson L, Armstrong BK, Butterfield DA, et al. Insufficient sun exposure has become a real public health problem. Int J Environ Res Public Health. 2020;17(14):5014.
  16. Scott TL, Masser BM, Pachana NA. Positive aging benefits of home and community gardening activities: older adults report enhanced self-esteem, productive endeavours, social engagement and exercise. SAGE Open Med. 2020;8:2050312120901732.
  17. Koblinsky ND, Meusel LAC, Greenwood CE, Anderson ND. Household physical activity is positively associated with gray matter volume in older adults. BMC Geriatr. 2021;21(1).