Supplement-based nutritional strategies to tackle frailty: A multifactorial, double-blind, randomized placebo-controlled trial Academic Article uri icon

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  • Background

    Sarcopenia plays a central role in the development of frailty syndrome. Nutrition and exercise are cornerstone strategies to mitigate the transition to frailty; however, there is a paucity of evidence for which dietary and exercise strategies are effective.


    This large, multifactorial trial investigated the efficacy of different dietary strategies to enhance the adaptations to resistance training in pre-frail and frail elderly.


    This was a single-site 16-week, double-blind, randomized, placebo-controlled trial conducted at the Clinical Hospital, School of Medicine - University of São Paulo, Sao Paulo, Brazil. Four integrated, sub-investigations were conducted to compare: 1) leucine vs. placebo; 2) whey vs. soy vs. placebo; 3) creatine vs. whey vs. creatine plus whey vs. placebo; 4) women vs. men in response to whey. Sub-investigations 1 to 3 were conducted in women, only. Two-hundred participants (154 women/46 men, mean age 72 ± 6 years) underwent a twice-a-week, resistance training program. The main outcomes were muscle function (assessed by dynamic and isometric strength and functional tests) and lean mass (assessed by DXA). Muscle cross-sectional area, health-related quality of life, bone and fat mass, and biochemical markers were also assessed.


    We observed that leucine supplementation was ineffective to improve muscle mass and function. Supplementation with whey and soy failed to enhance resistance-training effects. Similarly, supplementation with neither whey nor creatine potentiated the adaptations to resistance training. Finally, no sex-based differences were found in response to whey supplementation. Resistance exercise per se increased muscle mass and function in all sub-investigations. There were no adverse effects.


    Neither protein (whey and soy), leucine, nor creatine supplementation enhanced resistance training-induced adaptations in pre-frail and frail elderly, regardless of sex. These findings do not support the notion that some widely used supplement-based interventions can add to the already potent effects of resistance exercise to counteract frailty-related muscle wasting and dynapenia.

    Clinical trial registry


    Data sharing

    Data described in the manuscript will be made available upon request pending application.


  • Roschel, Hamilton
  • Hayashi, Ana Paula
  • Fernandes, Alan L
  • Jambassi-Filho, José Claudio
  • Hevia-Larraín, Victoria
  • de Capitani, Mariana
  • Santana, Davi A
  • Gonçalves, Lívia S
  • de Sá-Pinto, Ana Lúcia
  • Lima, Fernanda R
  • Sapienza, Marcelo T
  • Duarte, Alberto JS
  • Pereira, Rosa MR
  • Phillips, Stuart
  • Gualano, Bruno

publication date

  • August 2021