Immune Function and Muscle Adaptations to Resistance exercise in Older Adults: Study Protocol for a Randomized Controlled Trial of a Nutritional Supplement

Richard A Dennis, Usha Ponnappan, Ralph L Kodell, Kimberly K Garner, Christopher M Parkes, Melinda M Bopp, Kalpana P Padala, Charlotte A Peterson, Prasad R Padala, Dennis H Sullivan, Richard A Dennis, Usha Ponnappan, Ralph L Kodell, Kimberly K Garner, Christopher M Parkes, Melinda M Bopp, Kalpana P Padala, Charlotte A Peterson, Prasad R Padala, Dennis H Sullivan

Abstract

Background: Immune function may influence the ability of older adults to maintain or improve muscle mass, strength, and function during aging. Thus, nutritional supplementation that supports the immune system could complement resistance exercise as an intervention for age-associated muscle loss. The current study will determine the relationship between immune function and exercise training outcomes for older adults who consume a nutritional supplement or placebo during resistance training and post-training follow-up. The supplement was chosen due to evidence suggesting its ingredients [arginine (Arg), glutamine (Gln), and β-hydroxy β-methylbutyrate (HMB)] can improve immune function, promote muscle growth, and counteract muscle loss.

Methods/design: Veterans (age 60 to 80 yrs, N = 50) of the United States military will participate in a randomized double-blind placebo-controlled trial of consumption of a nutritional supplement or placebo during completion of three study objectives: 1) determine if 2 weeks of supplementation improve immune function measured as the response to vaccination and systemic and cellular responses to acute resistance exercise; 2) determine if supplementation during 36 sessions of resistance training boosts gains in muscle size, strength, and function; and 3) determine if continued supplementation for 26 weeks post-training promotes retention of training-induced gains in muscle size, strength, and function. Analyses of the results for these objectives will determine the relationship between immune function and the training outcomes. Participants will undergo nine blood draws and five muscle (vastus lateralis) biopsies so that the effects of the supplement on immune function and the systemic and cellular responses to exercise can be measured.

Discussion: Exercise has known effects on immune function. However, the study will attempt to modulate immune function using a nutritional supplement and determine the effects on training outcomes. The study will also examine post-training benefit retention, an important issue for older adults, usually omitted from exercise studies. The study will potentially advance our understanding of the mechanisms of muscle gain and loss in older adults, but more importantly, a nutritional intervention will be evaluated as a complement to exercise for supporting muscle health during aging.

Trial registration: Clinicaltrials.gov identifier: NCT02261961, registration date 10 June 2014, recruitment active.

Figures

Figure 1
Figure 1
Study objectives for a randomized trial of a nutritional supplement designed to determine if immune function influences the ability of older adults to improve muscle mass, strength, function, and cellular adaptation to resistance exercise training.
Figure 2
Figure 2
Relationships between pretraining muscle molecular and cellular measures and percent strength gain after 12 weeks of high-intensity progressive resistance training of the thigh muscles for older adults (N = 7, Age 69 ± 6 yrs). (A). Pearson correlation between the number of macrophages and IGF1 mRNA. The number of macrophages staining positive for CD163 by immunohistochemistry were counted per myofiber. IGF1 mRNA was measured using quantitative real-time reverse transcriptase polymerase chain reaction. (B). Pearson correlation between the number of muscle macrophages and strength gain for knee extension. One outlier was excluded from these analyses due to having macrophage levels that were fourfold higher than the group average.
Figure 3
Figure 3
Proposed model for how a nutritional supplement promotes a shift in immune system function in older adults from a pro-inflammatory state (both at rest and in response to a bout of exercise) towards a state in which inflammation is dampened so that muscle growth in response to exercise training is supported. The supplement is proposed to augment muscle adaptation and performance gains from resistance training by altering macrophage and muscle cell phenotype through specific cytokines, growth factors, and signaling pathways.
Figure 4
Figure 4
Timeline for individual subject participation. Each individual will participate in the study for approximately one year. Participation will include consumption of a nutritional supplement or placebo twice daily for 42 weeks. During this time, subjects will also complete 12 weeks of resistance training followed by 26 weeks of post-training follow-up (that is, a detraining period). The particular procedures and assessments involved during each week of participation are listed. X/X denotes assessment of response to a single bout of exercise by collecting specimens before and after exercise for blood (1 hour) and muscle (72 hours). The scheduling timeline is approximate and can be extended based on the scheduling needs of the subjects and study staff.

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