New insights on the role of omega-3, vitamin D and exercise in reducing the risk of pre-frailty in older adults

By:  Talking Nutrition Editors



  • Advances in medicine have led to a growing population of elderly individuals, and as a result, the prevalence of age-related malnutrition and frailty is becoming an increasing concern
  • Suboptimal nutrition and increased immobility in the elderly is associated with an increased risk of developing frailty and non-communicable diseases.1  However, evidence exploring these links is scarce and limited.
  • Discover the latest findings from the DO-HEALTH randomized clinical trial and supporting literature, demonstrating how supplementation with vitamin D and omega-3 fatty acids, alongside increased exercise could reduce the development of pre-frailty in robust, generally healthy and active older adults.

The frailty syndrome explained

As the global aging population increases, so does the age-related medical syndrome known as frailty. The term “frailty” or “being frail” refers to a clinically recognizable state of increased vulnerability resulting from an age-associated decline in physical function, such that the ability to cope with every day activity is compromised. Today, around 10% of people aged over 65 live with frailty – and this rises to 25-50% for those aged over 85.2

Frailty is often characterized by unintentional weight loss (including reduced muscle mass and strength), slow walking speed and fatigue (exhaustion and low physical activity), which reduces the quality of life of many older adults and poses a significant strain to healthcare systems.3,4 As such, lowering the risk of the onset of frailty with low-cost interventions, such as medical nutrition solutions and increased exercise, could transform the lives of many older adults at risk of developing this age-related condition. Although literature suggests exercise and nutrients such as vitamin D and omega-3 fatty acids could reduce the occurrence of frailty5,6,7,8, evidence is scarce, limited and often lacks validation from randomized controlled trials. Read on to learn about a new research analysis of the DO-HEALTH randomized clinical trial, which aimed to investigate the links between essential nutrients and exercise on the incidence of pre-frailty and frailty in a large cohort of robust older adults.

New insights: preventing age-related pre-frailty 

A new study by Gagesch et al., has shown – for the first time – the combined role of vitamin D, omega-3 fatty acids and exercise in decreasing the risk of pre-frailty.9 The study utilized data from the DO-HEALTH trial, a three-year, double-blind, randomized controlled clinical trial comprising 2,157 participants aged 70 and over. Participants were split into groups receiving 2000 IU/day of vitamin D3, 1 g/day of omega-3s comprising eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) at a ratio of 1:2, a simple home exercise program (SHEP) involving 30 minutes of strength-training exercise three times a week, alone or in combination, or placebo.

Over the course of the trial, frailty status was assessed at baseline and annually according to the five features of the physical frailty phenotype – weakness, fatigue, involuntary weight loss, low gait speed and low activity level.10  Zero of the five domains were classified as robust, whereas participants with one or two domains were classified as being pre-frail, and those with three or more domains as frail. Around 50% of the participants were categorized as robust at baseline and were included in the analysis. Of the robust participants at baseline, 61.2% became pre-frail over the three-year follow up period and 2.6% became frail. 

Findings revealed that the odds ratio (OR)* of developing pre-frailty for each individual intervention were 0.81, 0.84 and 0.89 for vitamin D, omega-3 and SHEP, respectively, compared to placebo. While these data indicate that each individual intervention could not significantly reduce occurrence of pre-frailty, a definite trend for reduced OR, and thus reduced risk, was observed in each group. Most importantly, the study shows that the combination of all three interventions significantly reduced the occurrence of pre-frailty with an OR of 0.61 compared to the placebo group. This highlights the importance of the additive effect of the three strategies in reducing the risk of pre-frailty.

Gagesch and team next assessed the effect of each intervention on frailty, but as limited participants became frail (2.6%), the study could not accurately determine the odds of frailty and was therefore unable to detect beneficial effects extending from pre-frailty to frailty. Nevertheless, analysis potentially indicated that omega-3 either alone – or in combination with vitamin D – may be helpful in reducing the OR of becoming frail.

dsm-firmenich’s Senior Scientist, Ines Warnke (nutritionist by training) comments: “The study indicates that vitamin D, omega-3s and exercise are an important combination for reducing the risk of the onset of pre-frailty. Optimal vitamin D status is difficult to achieve through diet alone, especially for the elderly as they require higher intakes of this vitamin. It is therefore advisable that the elderly population are regularly screened for the risk of pre-frailty, frailty, and vitamin D deficiency, so that supplementation can be administered to individuals with insufficient nutrient status. Ines continues: “Aside from vitamin D and reducing polypharmacy, a major contributor to the pathogenesis of frailty11, the study highlights that omega-3 supplementation and regular exercise should also be taken into consideration when trying to prevent the occurrence of pre-frailty. On top of this, there is evidence suggesting that B-vitamins, lutein, and zeaxanthin – among many more micronutrients - are important for maintaining health in the elderly, and as such, the nutritional status of elderly individuals should be closely monitored.” 12,13 dsm-firmenich’s Senior Manager in Health and Wellness, Marco Turini also notes: “In fact, some countries are already implementing similar techniques, with Switzerland recommending that all adults aged over 65 take a daily supplemental vitamin D dose of 800 IU.” 14

Is a healthy lifestyle key to healthy aging?

Physical activity and nutritional status of the elderly are crucial modifiable factors that can have a wider impact on health and quality of life. Exercise has been shown to reduce inflammation and increase protein synthesis in muscles, which improves muscle strength – reducing the occurrence of frailty syndrome.15 On the other hand, suboptimal nutrition is a contributing component to the prevalence and severity of non-communicable diseases, including cardiovascular, cognitive, musculoskeletal, immune, metabolic and ophthalmological functions.16 Malnutrition is more prevalent in elderly populations and in the UK, it is estimated that over 10% of people aged over 65 are malnourished, with this figure rising to 54% in certain parts of the world.17,18

dsm-firmenich’s lead scientist , Carole Springett (dietician by training), comments on why malnutrition is increasingly prevalent among the elderly: “As we age, several physiological changes occur and these can have negative implications on nutritional status.19 For example, our senses can become impaired, including the sense of taste and smell, leading to reduced appetite. Also, a loss of vision and hearing as we age can impair mobility, which can in turn impact our ability to go food shopping and cook meals. Moreover, poor oral health and dental problems can lead to inflammation and difficulty chewing food. All these factors can increase the risk of malnutrition in the elderly.”

Several studies have shown that a healthy diet and adequate nutrient intake can help reduce the risk of malnutrition and promote healthy aging. One such study exploring the role of nutrition in the elderly has shown that certain diets are associated with superior nutritional status, quality of life and increased survival among older adults. Such foods include low-fat dairy products, fruits, whole grains, poultry, fish and vegetables, and lower intake of meat, fried foods, sweets, high-energy drinks and added fats.20 Another study investigating the role of nutrition in a cohort of elderly adults with age-related vulnerabilities, including frailty, found that an intervention with customized nutritional support could significantly reduce the risk of mortality and other adverse clinical outcomes.21

Important findings from a recent review assessing the available literature on nutrition and healthy aging in Asia-Pacific regions found that optimal nutrition status needs to be met before reaching an elderly age and before the consequences of malnutrition-related diseases arise.22 As such, when diet alone is not enough to reach the required levels of nutrition, micronutrient supplements for adults, before reaching an elderly age, could help to reduce the outcome of malnutrition-related illness.

Looking for innovative ways to support elderly individuals? 

dsm-firmenich can support customers looking to create medical nutrition solutions for the elderly, with science-backed high-quality products that are insight-led. Click here to learn more about our tailored medical nutrition solutions.

*Odds Ratio (OR) was used to measure the relative occurrence of frailty. An OR<1 indicates that the intervention reduced occurrence of frailty compared to placebo (the smaller the OR the greater the effect).

Published on

23 March 2023


7 min read

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  1. Inui et al., The Role of Micronutrients in Ageing Asia: What Can Be Implemented with the Existing Insights. Nutrients. 13(7):2222 (2021).
  2. Understanding Frailty. Available at: What is frailty? | Age UK [last accessed Feb 2023].
  3. Lewis, E. et al. The prevalence and characteristics of frailty by frailty phenotype in rural Tanzania. BMC Geriatr 18, 283 (2018). 
  4. Morley et al., Frailty consensus: a call to action. J Am Med Dir Assoc. 14(6):392-7 (2013).
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  10. Fried et al., Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 56(3):M146-56 (2001).
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  13. Murphy, CH. et al., Plasma lutein and zeaxanthin concentrations associated with musculoskeletal health and incident frailty in The Irish Longitudinal Study on Ageing (TILDA). Experimental Gerontology. 171: 112013 (2023).
  14. Gordon-Seymour, N. Swiss government recommends high vitamin D intake for those over 65. Nutra Ingredients. Last updated 21st February 2022. Available at: Swiss government advises high vitamin D intake for over 65s ( [last accessed: 14th March 2023].
  15. Aguirre LE, Villareal DT. Physical Exercise as Therapy for Frailty. Nestle Nutr Inst Workshop Ser. 83:83-92 (2015). 
  16. Inui et al., The Role of Micronutrients in Ageing Asia: What Can Be Implemented with the Existing Insights. Nutrients. 13(7):2222 (2021).
  17. Malnutrition, Age UK. Available at Malnutrition information and support | Age UK [Last accessed: February 2023].
  18. Krishnamoorthy et al., Prevalence of malnutrition and its associated factors among elderly population in rural Puducherry using mini-nutritional assessment questionnaire. J Family Med Prim Care. 7(6):1429-1433 (2018).
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  22. Inui et al., The Role of Micronutrients in Ageing Asia: What Can Be Implemented with the Existing Insights. Nutrients. 13(7):2222 (2021).

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