1.
Impact of probiotics on muscle mass, muscle strength and lean mass: a systematic review and meta-analysis of randomized controlled trials.
Prokopidis, K, Giannos, P, Kirwan, R, Ispoglou, T, Galli, F, Witard, OC, Triantafyllidis, KK, Kechagias, KS, Morwani-Mangnani, J, Ticinesi, A, et al
Journal of cachexia, sarcopenia and muscle. 2023;14(1):30-44
-
-
-
-
Free full text
-
Plain language summary
Sarcopenia is a progressive skeletal muscle disorder involving accelerated loss of muscle mass, strength and function. It generally occurs in older age groups but can also be seen in younger people. Multiple factors contribute to the development of the condition. Besides nutritional management strategies, probiotics have recently caught the interest of researchers. As probiotics promote metabolic building activity, aid digestion and absorption and reduce muscle breakdown by favourably managing inflammation, they present great potential for the management of sarcopenia. This systematic review and meta-analysis explored the impact of probiotic supplementation on muscle mass, total lean mass and muscle strength in human adults. The review included 24 studies, with probiotics mainly from the Bifidobacteria or Lactobacilli family. The analysis concluded that probiotic supplementation improved muscle mass in comparison to placebos. It also significantly increased overall muscle strength in 6 randomized controlled trials, which was most obvious in age groups of 50 and above. However, no changes were seen concerning total lean mass. It appeared that longer studies, of >12 weeks or more, showed better outcomes in this review. Furthermore, Bifidobacteria species seemed to exhibit more favourable effects, and the authors also noted the beneficial results were more significant in Asian populations. Further research is needed to understand more about the underlying mechanism, best probiotics strains and the specifics of different demographic groups. This article yields a concise overview of sarcopenia, the nutritional aspects of the disease and how probiotics may be beneficial in disease management, strengthened with data from the review.
Expert Review
Conflicts of interest:
None
Take Home Message:
- This was a well-conducted meta-analysis based on its methodological approach that demonstrated that Lactobacillus and Bifidobacterium probiotic supplementation may contribute to improved muscle mass in younger adults and improved muscle strength in older adults.
- Bifidobacterium probiotic supplementation was associated with enhanced muscle mass in younger adults, a potential focus for those considering probiotic supplements.
- The duration of probiotic therapy matters, with longer-term (12 weeks or more) supplementation showing improvements in muscle mass and strength..
Evidence Category:
-
X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
-
B: Systematic reviews including RCTs of limited number
-
C: Non-randomized trials, observational studies, narrative reviews
-
D: Case-reports, evidence-based clinical findings
-
E: Opinion piece, other
Summary Review:
Introduction
This systematic review and meta-analysis evaluated the effect of probiotics on muscle mass, total lean mass and muscle strength in both young and older adults.
Methods
- The search encompassed PubMed, Scopus, Web of Science, and Cochrane Library databases, from inception up to June 2022; studies included spanned a period from 2013 to June 2022.
- The study adhered to Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines and included the Risk-of-Bias tool to assess study quality.
- The study focused on changes in muscle mass, total lean mass, and muscle strength.
- Inclusion criteria: randomised controlled trials (RCTs) with adult participants (>18 years); interventions involving any probiotics, and a control group receiving either no treatment or a placebo.
Results
- 24 RCTs were included (709 participants), with studies conducted in Europe, USA, and Asia. Intervention durations: ranged from 3 weeks to 12 months.
- Participants included overweight, untrained healthy and resistance-trained individuals, and those with specific conditions like metabolic syndrome and frailty.
- Body composition assessments were conducted using bioelectrical impedance (BIA) and/or dual-energy X-ray absorptiometry (DXA).
- Probiotic strains employed in the included studies varied, with Lactobacillus the most common, followed by Bifidobacterium; some combined both. 5 of 24 studies also used additional strains.
- Dosages: ranged from 2 × 10^9 to 11.2 × 10^10 colony-forming units (CFU).
- 4 out of 24 studies used fermented food products like cheese and noodles as sources of probiotics.
- 22 RCTs measured muscle mass and total lean mass; 6 RCTs measured global muscle strength.
- Probiotic supplementation (≥12 weeks) moderately increased muscle mass, with a standardised mean difference (SMD) of 0.42. This significant effect (95% CI: 0.10–0.74, P=0.009) was observed only in younger Asian adults (<50 years) after Bifidobacterium supplementation, based on a meta-analysis of 10 studies.
- Probiotic supplementation (≥12 weeks) significantly increased global muscle strength in older adults (>50 years; SMD: 0.69, 95% CI: 0.33–1.06, P = 0.0002).
- Probiotic supplementation showed no significant impact on lean mass (SMD: -0.03, 95% CI: 0.19 – 0.13, P = 0.69).
Conclusion
Probiotic supplementation, especially Lactobacillus and Bifidobacterium may have a positive impact on muscle mass and global strength
Clinical practice applications:
- Consumption of probiotics, mainly Lactobacillus and Bifidobacterium may contribute to improved muscle strength in older individuals (>50y).
- Consumption of Bifidobacterium strains was associated with improved muscle mass in younger individuals (<50y) in Asian countries, in a low number of studies (k=2).
- Bifidobacterium breve B-3 was associated with an improvement in muscle mass in older overweight individuals, although a causal relationship was not established.
- Probiotics may enhance muscle mass or strength by enhancing protein digestion and amino acid absorption for muscle synthesis and function.
- Considering an individual’s goals, a practitioner could consider probiotic supplementation as a complementary intervention when aiming to enhance muscle mass or strength .
Considerations for future research:
- Future research could focus on pinpointing which specific probiotic strains are most effective for muscle strength or muscle mass to tailor more precise interventions.
- Most studies did not exceed 12 weeks, highlighting the need for long-term research on probiotics sustained muscle impact.
- Future research could investigate the effects of probiotics across diverse demographic groups including different ages, sexes, and ethnic backgrounds to understand the impact in different populations.
- Delving deeper into the mechanisms by which probiotics influence muscle health could lead to targeted probiotic therapies that address specific physiological pathways.
- Finally, future research could explore how probiotics can be combined with other interventions, such as exercise or nutritional modifications, to synergistically improve muscle health and function.
Abstract
Probiotics have shown potential to counteract sarcopenia, although the extent to which they can influence domains of sarcopenia such as muscle mass and strength in humans is unclear. The aim of this systematic review and meta-analysis was to explore the impact of probiotic supplementation on muscle mass, total lean mass and muscle strength in human adults. A literature search of randomized controlled trials (RCTs) was conducted through PubMed, Scopus, Web of Science and Cochrane Library from inception until June 2022. Eligible RCTs compared the effect of probiotic supplementation versus placebo on muscle and total lean mass and global muscle strength (composite score of all muscle strength outcomes) in adults (>18 years). To evaluate the differences between groups, a meta-analysis was conducted using the random effects inverse-variance model by utilizing standardized mean differences. Twenty-four studies were included in the systematic review and meta-analysis exploring the effects of probiotics on muscle mass, total lean mass and global muscle strength. Our main analysis (k = 10) revealed that muscle mass was improved following probiotics compared with placebo (SMD: 0.42, 95% CI: 0.10-0.74, I2 = 57%, P = 0.009), although no changes were revealed in relation to total lean mass (k = 12; SMD: -0.03, 95% CI: -0.19 - 0.13, I2 = 0%, P = 0.69). Interestingly, a significant increase in global muscle strength was also observed among six RCTs (SMD: 0.69, 95% CI: 0.33-1.06, I2 = 64%, P = 0.0002). Probiotic supplementation enhances both muscle mass and global muscle strength; however, no beneficial effects were observed in total lean mass. Investigating the physiological mechanisms underpinning different ageing groups and elucidating appropriate probiotic strains for optimal gains in muscle mass and strength are warranted.
2.
Effects of an educational intervention on frailty status, physical function, physical activity, sleep patterns, and nutritional status of older adults with frailty or pre-frailty: the FRAGSALUD study.
Casals, C, Ávila-Cabeza-de-Vaca, L, González-Mariscal, A, Marín-Galindo, A, Costilla, M, Ponce-Gonzalez, JG, Vázquez-Sánchez, MÁ, Corral-Pérez, J
Frontiers in public health. 2023;11:1267666
-
-
-
-
Free full text
Plain language summary
Frailty and pre-frailty are associated with an increased risk of premature mortality. Factors involved in the development of frailty include physical activity, sleep and nutrition. The aim of this 6-month randomised controlled trial was to evaluate the effects of an educational programme on frailty, physical function, physical activity, sleep and nutritional status. 166 community-dwelling individuals aged 65 years or over with frailty or pre-frailty were randomised to either receive a health education programme consisting of 4 group sessions in the first month which included guidelines for physical activity, nutrition and cognitive training as well as the promotion of psychological and social wellbeing and 6 follow-up calls over 6 months or their usual healthcare (control). Compared to the control group, the intervention group had significant reductions in frailty score, exhaustion and fatigue score, increase in gait speed and improvements in various physical function tests. The intervention group also showed significant improvements in mini nutritional assessment compared to the control group although this was not associated with significant changes in anthropometric parameters. There was a significant increase in awakenings in the control group whilst this parameter did not change in the intervention group, whilst there were no changes in other sleep parameters. The authors concluded that the simplicity, affordability and effectiveness of the health education programme may contribute to healthy ageing.
Expert Review
Conflicts of interest:
None
Take Home Message:
To improve frailty and physical functioning, a comprehensive programme may be effective, which includes:
- Nutrition
- Physical exercise
- Cognitive training
- Promotion of social and psychological wellbeing.
Evidence Category:
-
X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
-
B: Systematic reviews including RCTs of limited number
-
C: Non-randomized trials, observational studies, narrative reviews
-
D: Case-reports, evidence-based clinical findings
-
E: Opinion piece, other
Summary Review:
Introduction
- Frailty and pre-frailty increase the risk of premature mortality but are reversible
- The aim of this study was to evaluate the effects of a health education programme on frailty status in frail or pre-frail older persons.
Methods
- Randomised controlled trial
- Participants: 166 community-dwelling individuals aged 65 years or over with frailty or pre-frailty living in Spain were enrolled, 163 completed the study (80 in intervention and 83 in control group)
- Four weekly group sessions which included guidelines for physical activity, nutrition and cognitive training as well as the promotion of psychological and social wellbeing and 6 follow-up calls over 6 months versus usual healthcare (control).
Results
- Baseline demographics: The educational group consisted of more women (p=0.001), had a younger average age (p=0.019), lower height (p=0.001) and a higher average education level (p=0.013) compared to the control group.
Effects on intervention group:
- Reductions in frailty score (p<0.05 vs baseline and change vs change in control group), with 30% of participants in the intervention group no longer being classified as frail or pre-frail in contrast to none in the control group
- Reductions in fatigue and exhaustion score (p<0.05 vs baseline and change vs change in control group)
- Increase in gait speed and improvements in various physical function tests (all p<0.05 vs baseline and change vs change in control group)
- Improvements in mini nutritional assessment (p<0.001 vs baseline and change vs change in control group)
- Improvement in sleep behaviour demonstrated by an increase in awakenings in the control group (p<0.05 vs baseline and change vs change in intervention group) whilst this parameter did not change in the intervention group.
No effects (vs control) on:
- Anthropometric parameters/unintended weight loss
- Other sleep parameters
- Physical activity expenditure and physical activity score
- Hand grip strength.
Conclusion
This affordable and simple health education programme is effective in reducing frailty in elderly and may contribute to healthy ageing.
Clinical practice applications:
- A comprehensive programme, encompassing not only nutrition, but also exercise, cognitive training and a focus on social and psychological wellbeing may be most effective in improving frailty and physical functioning
- Nutrition intervention, alongside other lifestyle interventions, may have benefits for nutritional status in older adults, even if this is not reflected in a change in anthropometric parameters, such as weight.
Considerations for future research:
- Studies with longer-term follow-up would help evaluate whether/for how long the benefits are sustained.
Abstract
INTRODUCTION The prevalence of frailty is increasing worldwide, emphasizing the importance of prioritizing healthy ageing. To address this, cost-effective and minimally supervised interventions are being sought. This study aimed to assess the impact of an educational program on frailty status, physical function, physical activity, sleep patterns, and nutritional status in community-dwelling older adults with at least 1 Fried's frailty criteria. METHODS A 6-month multicentre randomized controlled trial was conducted from March 2022 to February 2023 in 14 health centres located in Cadiz and Malaga, Spain. The educational intervention consisted of 4 group sessions and 6 follow-up phone calls spread over 6 months. The program focused on educating participants about frailty and its impact on health, providing guidelines for physical activity, healthy dietary habits, cognitive training, psychological well-being and social activities. A total of 163 participants, divided into control (n = 80) and educational groups (n = 83) were assessed before and after the intervention. RESULTS The results showed a significant group-time interaction in the physical function evaluated with a large effect on Short Physical Performance Battery score (η2p = 0.179, -0.1 [-1.2-1.0] points for control group vs. 1.0 [0.0-3.0] points for educational group, p < 0.001), and an effect on the 4-meter gait test ((η2p = 0.122, 0.5 [0.1-0.0] s for control group vs. -0.4 [-0.5- -0.3] s for educational group, p < 0.001), and the 5-repetition sit-to-stand test (η2p = 0.136, 1.0 [0.0-1.2] s for control group vs. -4.3 [-7.0- -2.3] for educational group, p < 0.001). Additionally, the use of accelerometers to assess physical activity, inactivity, and sleep patterns revealed a significant small effect in the number of awakenings at night ((η2p = 0.040, 1.1 [-0.5-3.4] awakenings for control group vs. 0.0 [-2.2-0.0] awakenings for educational group, p = 0.009). The findings also highlighted a significant medium effect regarding malnutrition risk, which was assessed using the Mini-Nutritional Assessment score (η2p = 0.088, -0.7 [-2.3-1.5] points for control group vs. 1.5 [-0.5-3.0] points for educational group, p < 0.001). DISCUSSION Thus, the 6-month educational program effectively improved physical function, sleep patterns, and nutritional status compared to usual healthcare attendance in community-dwelling older adults with frailty or pre-frailty. These findings underscore the potential of minimally supervised interventions in promoting a healthy lifestyle in this vulnerable population.
3.
Mediterranean diet and structural neuroimaging biomarkers of Alzheimer's and cerebrovascular disease: A systematic review.
Gregory, S, Pullen, H, Ritchie, CW, Shannon, OM, Stevenson, EJ, Muniz-Terrera, G
Experimental gerontology. 2023;172:112065
-
-
-
-
Free full text
-
Plain language summary
Nearly a million people in the UK have Alzheimer's disease, the most common type of dementia. Mediterranean diet (MedDiet) adherence is associated with healthy brain ageing, a reduced stroke risk, and a lower incidence of dementia. Seven studies were included in this review to evaluate the effects of MedDiet on hippocampal volume and white matter hyperintensity volume, predictors of stroke and dementia. This systematic review did not reveal any associations between MedDiet adherence and hippocampal volume. However, there was a significant negative relationship between MedDiet adherence and white matter hyperintensity volume in two of the studies included. It is necessary to conduct more robust studies to investigate the associations between MedDiet adherence and structural brain imaging findings and understand the mechanisms behind dementia and other cerebrovascular diseases. This study could provide healthcare professionals with valuable information about the effects of increased MedDiet adherence on brain health, including its potential to delay neurodegenerative disease progression.
Expert Review
Conflicts of interest:
None
Take Home Message:
Due to inconclusive results on the associations between MedDiet adherence and AD and cerebrovascular related structural neuroimaging findings, specific recommendations for the MedDiet cannot be made on the basis of this study until further research has been completed.
Evidence Category:
-
X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
-
B: Systematic reviews including RCTs of limited number
-
C: Non-randomized trials, observational studies, narrative reviews
-
D: Case-reports, evidence-based clinical findings
-
E: Opinion piece, other
Summary Review:
Background:
Changes in hippocampal volume (HV) and white matter intensity volume (WMIV) have been identified as structural neuroimaging biomarkers of neurodegenerative disease such as Alzheimer’s Disease (AD) and Cerebrovascular disease (CVD) respectively. Evidence has shown adherence to the Mediterranean Diet (MedDiet) has been associated with reduced risk for strokes. This review evaluated the MedDiet in relation to HV and WMIV.
Methods:
The review followed PRISMA guidelines and was registered on PROSPERO. Literature searching resulted in seven studies published between 2012 and 2022, which met the inclusion criteria. Six studies analysed cross-sectional data and one analysed longitudinal data. The NIH Quality Assessment Tool for Observational and Cross-Sectional Studies was used to assess risk of bias.
Overall, the studies were rated as low-risk of bias with details of the research question, participant group exposure and outcome variables included. Due to moderate to high heterogeneity in some studies, a meta-analysis was deemed unsuitable and narrative synthesis was conducted to present the results.
Results:
Mean participant age ranged from 53.19 to 80.3 years and volunteers were healthy or had subjective cognitive decline and a few participants had dementia (n=46).
Hippocampal Volume:
Four studies included 20,077 participants and found no significant associations between MedDiet adherence and hippocampal volume. All four studies were cross-sectional from larger cohort studies. To establish causative relationships longitudinal and RCT trials are required.
White Matter Hyperintensity Volumes:
Four studies included 1938 participants. Two studies found a significant negative association between MedDiet and WMHV, demonstrating higher Mediterranean Scores were associated with lower level of WHMV. The other two studies found no significant associations.
Although the review methodology with a piloted search strategy was considered a key strength, the lack of meta-analysis as planned in the a priori protocol, due to minimal eligible studies and high heterogeneity was a limitation as well as the restriction of brain imaging outcomes.
Conclusion:
Overall, these results are inconclusive on the associations between the MedDiet and HV and WMHV, and identify a gap in the knowledge, therefore further research such as RCT’s remains a priority to further understand the impact diet may have on neuroimaging markers of AD and CVD.
Clinical practice applications:
There were no significant associations between MedDiet adherence and HV, which was surprising given the evidence stating adherence to the MedDiet is associated with a lower incidence of dementia and stroke. However all four studies were cross-sectional studies and in order to detect causal associations, longitudinal and RCT’s are needed. Two studies did show a significant association between higher MedDiet adherence and lower WMHV, whereas two studies reported no significant associations.
Caution needs to be taken when recommending the MedDiet specifically for a reduction in HV and WMHV until further research has been undertaken.
Considerations for future research:
Future research should consider:
- larger cohorts and participants from the Mediterranean region where lifelong adherence to the MedDiet is more likely.
- looking at other risk factors to include obesity, lack of activity, poor sleep quality and stress.
- evaluating different socio-economic status, which has been shown to impact dietary behaviour.
- alternative imaging outcomes such as cortical thinning, PET amyloid and tau.
- . gold standard for methodology in particular dietary analysis and scanning and outcome derivation.
Abstract
Previous studies have demonstrated an association between adherence to the Mediterranean diet (MedDiet) and better cognitive performance, lower incidence of dementia and lower Alzheimer's disease biomarker burden. The aim of this systematic review was to evaluate the evidence base for MedDiet associations with hippocampal volume and white matter hyperintensity volume (WMHV). We searched systematically for studies reporting on MedDiet and hippocampal volume or WMHV in MedLine, EMBASE, CINAHL and PsycInfo. Searches were initially carried out on 21st July 2021 with final searches run on 23rd November 2022. Risk of bias was assessed using the NIH Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Of an initial 112 papers identified, seven papers were eligible for inclusion in the review reporting on 21,933 participants. Four studies reported on hippocampal volume, with inconclusive or no associations seen with MedDiet adherence. Two studies found a significant association between higher MedDiet adherence and lower WMHV, while two other studies found no significant associations. Overall these results highlight a gap in our knowledge about the associations between the MedDiet and AD and cerebrovascular related structural neuroimaging findings.
4.
Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults.
Singh, A, D'Amico, D, Andreux, PA, Fouassier, AM, Blanco-Bose, W, Evans, M, Aebischer, P, Auwerx, J, Rinsch, C
Cell reports. Medicine. 2022;3(5):100633
-
-
-
-
Free full text
Plain language summary
A gradual decline in muscle mass and strength with aging is natural, however, environmental factors such as diet and exercise dictate the trajectory of the decline. Exercise and healthy nutrition are the primary interventions to prevent and manage age-associated decline in muscle health and metabolic diseases. This study was designed as a proof-of-concept investigation of the efficacy of long-term oral supplementation with urolithin A (UA) on physiological endpoints in middle-aged adults. This study is a randomised, double-blind, placebo-controlled study. An overweight middle-aged population with a high body mass index and average physical endurance was selected for the study. Results showed improved lower-body muscle strength in the hamstring skeletal muscle at both doses of UA. Furthermore, it positively impacted aerobic endurance and physical-performance measures such as walking distance. Authors conclude that supplementation with UA is safe and increases circulating levels of UA.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Mitochondrial dysfunction is associated with ageing and linked to deterioration of skeletal muscle and sarcopenia. Improving mitochondrial health may therefore help to improve muscle health as we age.
- Previous studies have demonstrated improvements in muscle endurance with long term UA intake in older adults (1) and the study by Singh et al. supports these findings in middle-aged adults.
- For middle-aged clients who are noticing a decline in muscle strength, exercise performance, or a general increase in fatigue, taking 500-1,000 mg UA daily for two to four months could lead to noticeable improvements in symptoms.
- The compounds from which UA is derived are also found in polyphenol-rich plant foods including pomegranates, berries and walnuts, therefore consuming these foods may be useful dietary additions for the same purpose.
- These findings are likely to be relevant for younger populations too, as mitophagy, which is part of the action of UA, contributes to the removal and recycling of dysfunctional mitochondria, allowing healthier intact mitochondria to take their place.
Evidence Category:
-
X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
-
B: Systematic reviews including RCTs of limited number
-
C: Non-randomized trials, observational studies, narrative reviews
-
D: Case-reports, evidence-based clinical findings
-
E: Opinion piece, other
Summary Review:
- Urolithin A (UA) is a microbiome metabolite – known as a postbiotic - of elligitannins and polyphenolic compounds found in some plant foods including pomegratate, berries and walnuts.
- In animal models, UA has previously been shown to have a range of potential health benefits involving induction of mitophagy and on mitochondrial function, as well as on disease states including osteoarthritis, inflammatory bowel disease, cardiovascular disease, and neurodegenerative disorders.
- The current study sought to establish proof-of-concept of the efficacy and safety of long-term UA supplementation on physiological endpoints in middle-aged adults.
- The primary outcome was peak power output and secondary outcomes included a range of clinical and physiological parameters linked to muscle strength, exercise tolerance and physical performance.
- The study tested UA in 500mg and 1000 mg doses against placebo in a 3-arm randomized-controlled trial in n= 88 subjects aged 40-64y who were healthy, overweight (BMI 25.0-34.9 kg/m2), sedentary, and who had a low VO2max at study inclusion. 79 subjects completed the study.
- Subjects were assessed at baseline, midpoint (2 months) and endpoint (4 months). In addition to the UA intervention, subjects were asked to maintain low physical activity status for the duration of the trial, and avoid pomegranates and supplements known to influence muscle performance (high protein, CoQ10m vitamin B3 or L-carnitine).
- Though a difference in peak power output (primary outcome) was not observed, muscle strength improved by up to c. 12% with 500 mg daily UA (p=0.027). With 1000 mg UA daily, aerobic endurance improved by up to 15% (p=0.03), gait speed increased by 7% (p=0.004), and in the 6-minute walk test subjects improved by 7% (p=0.008) and walked on average more than 30 additional meters, indicating a clinically meaningful difference in mobility.
- In addition, subjects in the UA groups had improved biomarkers of cellular health. With 1000 mg UA daily, inflammation was reduced (CRP, p<0.05; IFN-γ and TNF-α, both p<0.05). In addition, biomarkers of mitochondrial efficiency were also improved with 500 mg UA daily, Iing increased protein levels related to improved mitophagy, and expression of genes belonging to mitochondria.
- UA was deemed as safe and well tolerated at both 500 mg and 1000 mg doses for 4 months’ administration.
- A strength of the study was that the groups were balanced for all physiological parameters at baseline. However, the ratio of females was 2:1, and ethnicity was mainly western European. This may limit interpretation of the findings.
- All authors except one are either employees, board members or members of the scientific advisory board of Amazentis SA, who both manufacture Mitopure, the UA supplement used, and who funded this trial.
Clinical practice applications:
- Mitophagy is an important step in improving mitochondrial health. This study demonstrates the potential of UA to activate this pathway.
- In healthy middle-aged adults who are overweight or obese, sedentary and with low physical performance, oral UA supplementation at a sufficient dose and duration may:
- increase muscle strength
- increase mitophagy proteins in human skeletal muscle, as well as various other mitochondrial markers
- increase exercise performance and aerobic exercise
- be a valuable intervention to consider in clients who are suffering from mitochondrial dysfunction
Considerations for future research:
- This study was exploratory and the sample size for some of the outcomes was very small and inadequate to demonstrate true statistical significance. Future studies of similar design are needed to confirm the findings
- Nevertheless, the study was well-structured with carefully elaborated markers. It could be used as a template for future studies.
Abstract
Targeting mitophagy to activate the recycling of faulty mitochondria during aging is a strategy to mitigate muscle decline. We present results from a randomized, placebo-controlled trial in middle-aged adults where we administer a postbiotic compound Urolithin A (Mitopure), a known mitophagy activator, at two doses for 4 months (NCT03464500). The data show significant improvements in muscle strength (∼12%) with intake of Urolithin A. We observe clinically meaningful improvements with Urolithin A on aerobic endurance (peak oxygen oxygen consumption [VO2]) and physical performance (6 min walk test) but do not notice a significant improvement on peak power output (primary endpoint). Levels of plasma acylcarnitines and C-reactive proteins are significantly lower with Urolithin A, indicating higher mitochondrial efficiency and reduced inflammation. We also examine expression of proteins linked to mitophagy and mitochondrial metabolism in skeletal muscle and find a significant increase with Urolithin A administration. This study highlights the benefit of Urolithin A to improve muscle performance.