Effects of whey and soy protein supplementation on inflammatory cytokines in older adults: a systematic review and meta-analysis.

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• Nutritional strategies such as whey and soy protein supplementation may be regarded as safe and effective to attenuate adverse changes in muscle mass with ageing, however need to be considered alongside individual dietary intake and health status.
• Consider optimising protein intake and quality of protein through diet as an alternative or first line strategy.

Introduction

• A decline in muscle mass and physical capacity, known as sarcopenia, may start in the fourth decade with accumulation of adiposity, resulting in elevated circulating proinflammatory cytokines.
• Systematic and local elevation of oxidative stress and reactive oxygen species accumulation may accelerate age-related muscle wasting, however may be mitigated with antioxidant nutrients.
• This SR and MA evaluated whey and soy proteins effects on interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α) and C-reactive protein (CRP) in older adults.

Methods

SR followed PRISMA guidelines, was registered on PROSPERO and included 31 RCT studies published in English between 2004-21. Intervention group received soy/whey supplements and comparator group received a placebo; circulating levels of CRP, IL-6 and/or TNF-α were assessed. MA used random-effects to calculate the pooled effects. Overall quality of evidence was rated as moderate.

Results

Males and females with a mean age 50 - 80 years were included. Whey protein:

• IL-6 levels were reduced significantly (Number of studies (k) = 12, Mean Difference (MD): −0·79, 95 % Confidence Interval (CI): −1·15, −0·42, p< 0.01), however, high heterogeneity was observed (I2 = 96 %).
• Treatment duration ≤ 8 weeks showed a significant reduction in serum CRP (k = 4, MD: –0·30, 95 % CI: –0·39, –0·21, I2 = 0 %) compared with > 8 weeks (k = 6, MD: 0·13, 95 % CI: –0·13, 0·40, I2 = 9 %), whereas TNF-α and IL-6 remained unaltered.
• Individuals with sarcopenia and pre-frailty displayed a significant reduction of IL-6 (k = 3, MD: –0·98, 95 % CI: –1·56, –0·39, I2 = 0 %) but no benefits were observed for CRP or TNF.

Soy protein:

• There was a significant reduction in TNF-α (k = 6, MD: −0·16, 95 % CI: −0·26, p<0·05).
• The addition of isoflavones demonstrated a significant decrease in TNF-α (k = 5, MD: –0·20, 95 % CI: –0·31, –0·08, I2 = 34 %) but an increase in CRP (k = 7, MD: 0·53, 95 % CI: 0·12, 0·94), however high heterogeneity was observed in the latter (I2 = 91 %).

Conclusion

• The study found a significant reduction in IL-6 following whey protein with effects augmented in those with frailty and sarcopenia and a significant reduction in TNF-α following soy protein with effects augmented by additional soy isoflavones, possibly due to antioxidant effects.

• Consider whey and/or soy protein supplementation in older adults particularly those reported with pre-frailty and sarcopenia as an effective and safe strategy to attenuate low-grade inflammation and associated risks.
• Soy isoflavones may have additional antioxidant benefits for older adults although further research is needed to confirm this due to high heterogeneity found.

Future research could:

• Evaluate other factors which influence the inflammatory profile such as nutrient density, vitamins and minerals supplementation and exercise.
• Include those with co-morbidities and healthy populations with placebo comparator groups.
• Evaluate dose and type of soy isoflavones on circulating inflammatory markers and the effect of combined whey and soy protein.