The Effect of Boosting Dietary Lactobacillus and Phytochemical Rich Foods on Biomarkers of Longevity—A Phase II Randomised Placebo Controlled Trial
Abstract
1. Introduction
2. Materials and Methods
2.1. Participants
2.2. Randomisation and Masking
2.3. Procedures
2.4. End Points
2.5. Statistical Analysis
3. Results
3.1. Mean Grip Strength
3.2. Inflammation Measured via the Neutrophil to Lymphocyte Ratio (NLR)
3.3. Testosterone
3.4. Adverse and Other Events
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
| BMI | Body Mass Index |
| CI | Confidence Intervals |
| EGCG | Epigallocatechin gallate |
| GS | Grip Strength |
| IRAS | Integrative Research Application system |
| NLR | Neutrophil to Lymphocyte Ratio |
| PRS | Phytochemical Rich Supplement |
| P | Placebo |
| PB | Probiotic |
| PCA | Prostate Cancer |
| ROS | Reactive Oxygen Species (ROS) |
| SD | Standard Deviation |
References
- Finkel, T.; Holbrook, N.J. Oxidants, oxidative stress and the biology of ageing. Nature 2000, 408, 239–247. [Google Scholar] [CrossRef]
- López-Otín, C.; Blasco, M.A.; Partridge, L.; Serrano, M.; Kroemer, G. The hallmarks of aging. Cell 2013, 153, 1194–1217. [Google Scholar] [CrossRef] [PubMed]
- Buonacera, A.; Stancanelli, B.; Colaci, M.; Malatino, L. Neutrophil to lymphocyte ratio: An emerging marker of the relationships between the immune system and diseases. Int. J. Mol. Sci. 2022, 23, 3636. [Google Scholar] [CrossRef]
- Roberts, H.C.; Denison, H.J.; Martin, H.J.; Patel, H.P.; Syddall, H.; Cooper, C.; Sayer, A.A. A review of the measurement of grip strength in clinical and epidemiological studies: Towards a standardised approach. Age Ageing 2011, 40, 423–429. [Google Scholar] [CrossRef]
- Cheung, C.L.; Nguyen, U.S.; Au, E.; Tan, K.C.B.; Kung, A.W.C. Association of handgrip strength with chronic diseases and multimorbidity: A cross-sectional study. Age 2013, 35, 929–941. [Google Scholar] [CrossRef]
- Bohannon, R.W. Grip strength: An indispensable biomarker for older adults. Clin. Interv. Aging 2019, 14, 1681–1691. [Google Scholar] [CrossRef] [PubMed]
- Parra-Soto, S.; Pell, J.P.; Celis-Morales, C.; Ho, F.K. Absolute and relative grip strength as predictors of cancer: Prospective cohort study of 445 552 participants in UK Biobank. J. Cachexia Sarcopenia Muscle 2022, 13, 325–332. [Google Scholar] [CrossRef] [PubMed]
- Wilson, O.; Wojcik, K.M.; Kamil, D.; Gorzelitz, J.; Butera, G.; Matthews, C.E.; Jayasekera, J. The associations of muscle-strengthening exercise with recurrence and mortality among breast cancer survivors: A systematic review. Int. J. Behav. Nutr. Phys. Act. 2024, 21, 100. [Google Scholar] [CrossRef]
- Thomas, R.; Williams, M.; Aldous, J. Multiple biological mechanisms for the potential influence of phytochemicals on physical activity performance: A narrative review. Nutraceuticals 2023, 3, 353–365. [Google Scholar] [CrossRef]
- Thomas, R.; Kenfield, S.A.; Yanagisawa, Y.; Newton, R.U. Why exercise has a crucial role in cancer prevention, risk reduction and improved outcomes. Br. Med. Bull. 2021, 139, 100–119. [Google Scholar] [CrossRef]
- Zitzmann, M. Testosterone, mood, behaviour and quality of life. Andrology 2020, 8, 1598–1605. [Google Scholar] [CrossRef]
- Chiu, H.T.; Shih, M.T.; Chen, W.L. Examining the association between grip strength and testosterone. Aging Male 2020, 23, 915–922. [Google Scholar] [CrossRef]
- Shin, J.H.; Park, Y.H.; Sim, M.; Kim, S.-A.; Joung, H.; Shin, D.-M. Serum level of sex steroid hormone is associated with diversity and profiles of human gut microbiome. Res. Microbiol. 2019, 170, 192–201. [Google Scholar] [CrossRef] [PubMed]
- Matsushita, M.; Fujita, K.; Motooka, D.; Hatano, K.; Hata, J.; Nishimoto, M.; Banno, E.; Takezawa, K.; Fukuhara, S.; Kiuchi, H.; et al. Firmicutes in gut microbiota correlate with blood testosterone levels in elderly men. World J. Mens Health 2022, 40, 517–525. [Google Scholar] [CrossRef] [PubMed]
- Ammar, A.; Turki, M.; Chtourou, H.; Hammouda, O.; Trabelsi, K.; Kallel, C.; Abdelkarim, O.; Hoekelmann, A.; Bouaziz, M.; Ayadi, F.; et al. Pomegranate supplementation accelerates recovery of muscle damage and soreness and inflammatory markers after a weightlifting training session. PLoS ONE 2016, 11, e0160305. [Google Scholar] [CrossRef] [PubMed]
- Gonçalves, A.C.; Gaspar, D.; Flores-Félix, J.D.; Falcão, A.; Alves, G.; Silva, L.R. Effects of functional phenolics dietary supplementation on athletes’ performance and recovery: A review. Int. J. Mol. Sci. 2022, 23, 4652. [Google Scholar] [CrossRef]
- Malaguti, M.; Angeloni, C.; Hrelia, S. Polyphenols in exercise performance and prevention of exercise-induced muscle damage. Oxidative Med. Cell. Longev. 2013, 2013, 825928. [Google Scholar] [CrossRef]
- Braakhuis, A.J.; Somerville, V.X.; Hurst, R.D. The effect of New Zealand blackcurrant on sport performance and related biomarkers: A systematic review and meta-analysis. J. Int. Soc. Sports Nutr. 2020, 17, 25. [Google Scholar] [CrossRef]
- Davis, J.M.; Murphy, E.A.; Carmichael, M.D.; Zielinski, M.R.; Groschwitz, C.M.; Brown, A.S. Curcumin effects on inflammation and performance recovery following eccentric exercise-induced muscle damage. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2007, 292, R2168–R2173. [Google Scholar] [CrossRef]
- Jäger, R.; Mohr, A.E.; Carpenter, K.C.; Kerksick, C.M.; Purpura, M.; Moussa, A.; Townsend, J.R.; Lamprecht, M.; West, N.P.; Black, K.; et al. International society of sports nutrition position stand: Probiotics. J. Int. Soc. Sports Nutr. 2019, 16, 62. [Google Scholar] [CrossRef]
- Imperatrice, M.; Cuijpers, I.; Troost, F.J.; Sthijns, M.M. Hesperidin functions as an ergogenic aid by increasing endothelial function and decreasing exercise-induced oxidative stress and inflammation, thereby contributing to improved exercise performance. Nutrients 2022, 14, 2955. [Google Scholar] [CrossRef]
- Huang, W.C.; Chiu, W.C.; Chuang, H.L.; Tang, D.-W.; Lee, Z.-M.; Wei, L.; Chen, F.-A.; Huang, C.-C. Effect of curcumin supplementation on physiological fatigue and physical performance in mice. Nutrients 2015, 7, 905–921. [Google Scholar] [CrossRef]
- Trombold, J.R.; Reinfeld, A.S.; Casler, J.R.; Coyle, E.F. The effect of pomegranate juice supplementation on strength and soreness after eccentric exercise. J. Strength. Cond. Res. 2011, 25, 1782–1788. [Google Scholar] [CrossRef]
- Cermak, N.M.; Gibala, M.J.; van Loon, L.J.C. Nitrate supplementation’s improvement of 10-km time-trial performance in trained cyclists. Int. J. Sports Nutr. Exerc. Metab. 2012, 22, 64–71. [Google Scholar] [CrossRef]
- Jones, A. Dietary nitrate supplementation and exercise performance. Sports Med. 2014, 44, 35–45. [Google Scholar] [CrossRef]
- Bhattacharya, S.O.; Mandal, S.K.; Akhtar, M.S.; Dastider, D. Phytochemicals in the treatment of arthritis: Current knowledge. Int. J. Curr. Pharm. Res. 2020, 12, 1–6. [Google Scholar] [CrossRef]
- Zeng, L.; Yang, T.; Yang, K.; Yu, G.; Li, J.; Xiang, W.; Chen, H. Efficacy and safety of curcumin and Curcuma longa extract in the treatment of arthritis: A systematic review and meta-analysis of randomised controlled trials. Front. Immunol. 2022, 13, 891822. [Google Scholar] [CrossRef]
- Tian, Z.; Zhang, X.; Sun, M. Phytochemicals mediate autophagy against osteoarthritis by maintaining cartilage homeostasis. Front. Pharmacol. 2021, 12, 795058. [Google Scholar] [CrossRef] [PubMed]
- Arcanjo, N.O.; Andrade, M.J.; Padilla, P.; Rodríguez, A.; Madruga, M.S.; Estévez, M. Resveratrol protects Lactobacillus reuteri against H2O2-induced oxidative stress and stimulates antioxidant defences through upregulation of the dhaT gene. Free Radic. Biol. Med. 2019, 135, 38–45. [Google Scholar] [CrossRef]
- Davinelli, S.; Scapagnini, G. Interactions between dietary polyphenols and aging gut microbiota: A review. Biofactors 2022, 48, 274–284. [Google Scholar] [CrossRef] [PubMed]
- Alves-Santos, A.M.; Sugizaki, C.S.A.; Lima, N.; Naves, M.M.V. Prebiotic effect of dietary polyphenols: A systematic review. J. Funct. Foods 2020, 74, 104169. [Google Scholar] [CrossRef]
- Al Azzaz, J.; Al Tarraf, A.; Heumann, A.; Barreira, D.D.S.; Laurent, J.; Assifaoui, A.; Rieu, A.; Guzzo, J.; Lapaquette, P. Resveratrol favors adhesion and biofilm formation of Lacticaseibacillus paracasei subsp. paracasei strain ATCC334. Int. J. Mol. Sci. 2020, 21, 5423. [Google Scholar] [CrossRef]
- Scazzocchio, B.; Minghetti, L.; D’Archivio, M. Interaction between gut microbiota and curcumin: A new key of understanding for the health effects of curcumin. Nutrients 2020, 12, 2499. [Google Scholar] [CrossRef]
- Morrison, D.J. Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism. Gut Microbes 2016, 7, 189. [Google Scholar] [CrossRef] [PubMed]
- Gross, G.; Jacobs, D.M.; Peters, S.; Possemiers, S.; van Duynhoven, J.; Vaughan, E.E.; van de Wiele, T. In vitro bioconversion of polyphenols from black tea and red wine/grape juice by human intestinal microbiota displays strong interindividual variability. J. Agric. Food Chem. 2010, 58, 10236–10246. [Google Scholar] [CrossRef] [PubMed]
- Sugimura, Y.; Yang, Y.; Kanda, A.; Mawatari, A.; Tamada, Y.; Mikami, T.; Nakaji, S.; Ihara, K. Association between gut microbiota and muscle strength in Japanese general population of the Iwaki Health Promotion Project. Microorganisms 2024, 12, 622. [Google Scholar] [CrossRef]
- Barton, W.; Penney, N.C.; Cronin, O.; Garcia-Perez, I.; Molloy, M.G.; Holmes, E.; Shanahan, F.; Cotter, P.D.; O’Sullivan, O. The microbiome of professional athletes differs from that of more sedentary subjects in composition and particularly at the functional metabolic level. Gut 2018, 67, 625–633. [Google Scholar] [CrossRef]
- Lee, M.C.; Ho, C.S.; Hsu, Y.J.; Huang, C.C. Live and heat-killed probiotic Lactobacillus paracasei PS23 accelerated the improvement and recovery of strength and damage biomarkers after exercise-induced muscle damage. Nutrients 2022, 14, 4563. [Google Scholar] [CrossRef]
- Di Dio, M.; Calella, P.; Cerullo, G.; Pelullo, C.P.; Di Onofrio, V.; Gallè, F.; Liguori, G. Effects of probiotics supplementation on risk and severity of infections in athletes: A systematic review. Int. J. Environ. Environ. Res. Public Health 2022, 19, 11534. [Google Scholar] [CrossRef] [PubMed]
- Ale, E.C.; Binetti, A.G. Role of probiotics, prebiotics, and synbiotics in the elderly: Insights into their applications. Front. Microbiol. 2021, 12, 631254. [Google Scholar] [CrossRef]
- Kim, C.S.; Cha, L.; Sim, M.; Jung, S.; Chun, W.Y.; Baik, H.W.; Shin, D.-M.; Cha, L. Probiotic supplementation improves cognitive function and mood with changes in gut microbiota in community-dwelling older adults: A randomized, double-blind, placebo-controlled, multicenter trial. J. Gerontol. A Biol. Sci. Med. Sci. 2021, 76, 32–40. [Google Scholar] [CrossRef]
- Rahman, S.O.; Bariguian, F.; Mobasheri, A. The potential role of probiotics in the management of osteoarthritis pain: Current status and future prospects. Curr. Rheumatol. Rep. 2023, 25, 307–326. [Google Scholar] [CrossRef]
- Tangestani, H.; Boroujeni, H.K.; Djafarian, K.; Emamat, H.; Shab-Bidar, S. Vitamin D and The Gut Microbiota: A Narrative Literature Review. Clin. Nutr. Res. 2021, 10, 181–191. [Google Scholar] [CrossRef]
- Thomas, R.; Williams, M.; Sharma, H.; Chaudry, A.; Bellamy, P. A double-blind, placebo-controlled randomised trial evaluating the effect of a polyphenol-rich whole food supplement on PSA progression in men with prostate cancer—The U.K. NCRN Pomi-T study. Prostate Cancer Prostatic Dis. 2014, 17, 180–186. [Google Scholar] [CrossRef] [PubMed]
- Thomas, R.; Kenfield, S.A.; Williams, M.; Newton, R.U.; Aldous, J.; Mitra, A.; Fazili, Z. Increasing Phytochemical-rich Foods and Lactobacillus Probiotics in Men with Low-risk Prostate Cancer—A Randomised, Double-blind, Placebo-controlled Trial. Eur. Urol. Oncol. 2026, 9, 193–198. [Google Scholar] [CrossRef] [PubMed]
- Faul, F.; Erdfelder, E.; Lang, A.-G.; Buchner, A. G*Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav. Res. Methods 2007, 39, 175–191. [Google Scholar] [CrossRef] [PubMed]
- Thomas, R.; Williams, M.; Aldous, J.; Yanagisawa, Y.; Kumar, R.; Forsyth, R.; Chater, A. A randomised, double-blind, placebo-controlled trial evaluating concentrated phytochemical-rich nutritional capsule in addition to a probiotic capsule on clinical outcomes among individuals with COVID-19—The UK Phyto-V Study. COVID 2022, 2, 433–449. [Google Scholar] [CrossRef]

| Category (n = 208) | PRS+P (n = 103) | PRS+PB (n = 105) | Statistical Difference |
|---|---|---|---|
| Average age (74.2 years) | 76 | 73 | p = 0.02, 95% CI 1–6 years |
| Baseline grip strength | 31.1 kg | 36.4 kg | p = 0.03, 95% CI 3.9–4.8 |
| Age range (50–91 years) | 50–89 | 50–91 | NS |
| BMI (Kg/m2) | 27.2 | 27.5 | NS |
| White | 100 (97%) | 102 (97%) | NS |
| Non-white | 3 | 3 |
| Baseline | 4 Months | Percentage Score Difference Using Mixed Two-Way ANOVA Baseline vs. 4 Months | |
|---|---|---|---|
| Grip strength PRS+P (n = 103) | 31.1 kg (±8.7) | 33.7 (±9.1) | Mean Difference = 2.5 Kg (8%), p < 0.001, 95% CI 1.8–3.4). |
| Grip strength PRS+PB (n = 105) | 36.4 (±7.3) | 40.8 (±7.6) | Mean Difference = 4.4 Kg (11%), p < 0.001, 95% CI 3.6–5.2). |
| PRS+P (n = 103) | PRS+PB (n = 105) | Mean Difference (Mixed Two Way ANOVA) | |
|---|---|---|---|
| Grip strength change from baseline to 4 months | 2.5 Kg ±1.8–3.4 | 4.4 Kg ±3.6–5.2 | 2.5 Kg (57%), p < 0.001, 95% CI 0.8 to 3.0). |
| Serum testosterone at 4 months | 13.02 nmol/L ±6.99 | 14.75 nmol/L ±4.76 | 1.73 ng/L (12%) (p = 0.046, 95% CI 0.23 to 3.33). |
| Lymphocyte to neutrophil ratio change from baseline to 4 months | +0.39 | −0.41 | 0.79 (p = 0.04. 95% CI 0.03–1.53) |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2026 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.
Share and Cite
Thomas, R.J.; Williams, M.; Aldous, J.W.F.; Kenfield, S.A.; Newton, R.U. The Effect of Boosting Dietary Lactobacillus and Phytochemical Rich Foods on Biomarkers of Longevity—A Phase II Randomised Placebo Controlled Trial. J. Ageing Longev. 2026, 6, 35. https://doi.org/10.3390/jal6020035
Thomas RJ, Williams M, Aldous JWF, Kenfield SA, Newton RU. The Effect of Boosting Dietary Lactobacillus and Phytochemical Rich Foods on Biomarkers of Longevity—A Phase II Randomised Placebo Controlled Trial. Journal of Ageing and Longevity. 2026; 6(2):35. https://doi.org/10.3390/jal6020035
Chicago/Turabian StyleThomas, Robert J., Madeleine Williams, Jeffrey W. F. Aldous, Stacey A. Kenfield, and Robert U. Newton. 2026. "The Effect of Boosting Dietary Lactobacillus and Phytochemical Rich Foods on Biomarkers of Longevity—A Phase II Randomised Placebo Controlled Trial" Journal of Ageing and Longevity 6, no. 2: 35. https://doi.org/10.3390/jal6020035
APA StyleThomas, R. J., Williams, M., Aldous, J. W. F., Kenfield, S. A., & Newton, R. U. (2026). The Effect of Boosting Dietary Lactobacillus and Phytochemical Rich Foods on Biomarkers of Longevity—A Phase II Randomised Placebo Controlled Trial. Journal of Ageing and Longevity, 6(2), 35. https://doi.org/10.3390/jal6020035

