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Effects of whey and soy protein supplementation on inflammatory cytokines in older adults: a systematic review and meta-analysis.
Prokopidis, K, Mazidi, M, Sankaranarayanan, R, Tajik, B, McArdle, A, Isanejad, M
The British journal of nutrition. 2023;129(5):759-770
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Plain language summary
Reduced muscle mass and reduction in physical activity may lead to sarcopenia in older people. Age-related sarcopenia is associated with increased systemic low-grade inflammation and obesity. Protein supplementation is found to be beneficial in reducing circulating pro-inflammatory cytokines in old people. Previous research has shown that supplementation with isolated whey and soy protein reduces the levels of inflammatory cytokines in older adults. However, there is limited research on intact whey and soy protein supplementation in reducing age-related inflammation. This systematic review and meta-analysis investigated the effect of intact whey and soy protein on serum inflammatory markers such as C-reactive protein (CRP), Interleukin-6 (IL6) and TNF-α in older adults. The results of this meta-analysis show a significant reduction in circulating IL-6 and TNF-α levels after the supplementation with whey and soy protein. The addition of soy isoflavones resulted in a further decline in serum CRP levels. Subgroup analysis showed that the whey protein supplementation significantly improved sarcopenia and pre-frailty. Healthcare professionals can use the result of this systematic review and meta-analysis to understand the anti-inflammatory properties of intact whey and soy protein and soy isoflavones. However, further robust studies are required to assess the anti-inflammatory properties of whey and soy protein due to the high heterogeneity of included studies in this review.
Expert Review
Conflicts of interest:
None
Take Home Message:
- 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.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
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.
Clinical practice applications:
- 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.
Considerations for future research:
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.
Abstract
BACKGROUND AND AIMS Low-grade inflammation is a mediator of muscle proteostasis. This study aimed to investigate the effects of isolated whey and soy proteins on inflammatory markers. METHODS We conducted a systematic literature search of randomised controlled trials (RCT) through MEDLINE, Web of Science, Scopus and Cochrane Library databases from inception until September 2021. To determine the effectiveness of isolated proteins on circulating levels of C-reactive protein (CRP), IL-6 and TNF-α, a meta-analysis using a random-effects model was used to calculate the pooled effects (CRD42021252603). RESULTS Thirty-one RCT met the inclusion criteria and were included in the systematic review and meta-analysis. A significant reduction of circulating IL-6 levels following whey protein [Mean Difference (MD): -0·79, 95 % CI: -1·15, -0·42, I2 = 96 %] and TNF-α levels following soy protein supplementation (MD: -0·16, 95 % CI: -0·26, -0·05, I2 = 68 %) was observed. The addition of soy isoflavones exerted a further decline in circulating TNF-α levels (MD: -0·20, 95 % CI: -0·31, -0·08, I2 = 34 %). According to subgroup analysis, whey protein led to a statistically significant decrease in circulating IL-6 levels in individuals with sarcopenia and pre-frailty (MD: -0·98, 95 % CI: -1·56, -0·39, I2 = 0 %). These findings may be dependent on participant characteristics and treatment duration. CONCLUSIONS These data support that whey and soy protein supplementation elicit anti-inflammatory effects by reducing circulating IL-6 and TNF-α levels, respectively. This effect may be enhanced by soy isoflavones and may be more prominent in individuals with sarcopenia.
2.
Nutritional Interventions to Improve Asthma-Related Outcomes through Immunomodulation: A Systematic Review.
van Brakel, L, Mensink, RP, Wesseling, G, Plat, J
Nutrients. 2020;12(12)
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Asthma is a chronic inflammatory disease of the airways, with the infiltration of immune cells into the airways leading to localized inflammation and asthmatic symptoms. This review sought to establish whether nutritional interventions can help improve asthma and if this happens via regulation of the immune system. 28 studies were included that investigated the impact on both asthma and immunological parameters. The interventions include herbs (Nigella sativa, Crocus sativa, Boswellia serrata gum, Aegle marmelos), supplements (Vitamin E, soy isoflavones, tomato extract), weight loss and reduced-calorie diets, Vitamin D3, omega-3 fatty acids and whole-food approaches such as the Mediterranean diet. Half of the studies reported improvements in either asthma symptoms or immunological parameters. Two studies showed worsening. The herbal mixtures had the most consistent impact in both areas, followed by omega-3 fatty acids. Of interest here was that low to moderate dosages seemingly obtained wider-ranging improvements than higher dosages. The least evidence was found for vitamin D in the studies included. Overall only a couple of studies showed clinically relevant improvements and the authors insist that more research is needed before further nutritional interventions can be included in guidelines for asthma management. According to this review, the evidence for nutritional evidence for asthma management is still limited, in particular for those interventions where symptoms improvements correlate with beneficial immunological changes.
Abstract
Asthma is a chronic inflammatory disease of the airways, characterized by T-helper (Th) 2 inflammation. Current lifestyle recommendations for asthma patients are to consume a diet high in fruits and vegetables and to maintain a healthy weight. This raises the question of whether other nutritional interventions may also improve asthma-related outcomes and whether these changes occur via immunomodulation. Therefore, we systematically reviewed studies that reported both asthma-related outcomes as well as immunological parameters and searched for relations between these two domains. A systematic search identified 808 studies, of which 28 studies met the inclusion criteria. These studies were divided over six nutritional clusters: herbs, herbal mixtures and extracts (N = 6); supplements (N = 4); weight loss (N = 3); vitamin D3 (N = 5); omega-3 long-chain polyunsaturated fatty acids (LCPUFAs) (N = 5); and whole-food approaches (N = 5). Fifteen studies reported improvements in either asthma-related outcomes or immunological parameters, of which eight studies reported simultaneous improvements in both domains. Two studies reported worsening in either asthma-related outcomes or immunological parameters, of which one study reported a worsening in both domains. Promising interventions used herbs, herbal mixtures or extracts, and omega-3 LCPUFAs, although limited interventions resulted in clinically relevant results. Future studies should focus on further optimizing the beneficial effects of nutritional interventions in asthma patients, e.g., by considering the phenotypes and endotypes of asthma.