Cellular Longevity Complex

CLINICAL STUDIES ON THE FOLLOWING INGREDIENTS:

Urolithin A

Urolithin A, A Gut Microbiome Derived Compound Improves Mitochondrial Health And Muscle Performance

Abstract

Urolithin A (UA) is a natural gut microbiome derived metabolite generated upon consumption of foods rich in the ellagitannins such as berries, pomegranates, and walnuts. UA can naturally be produced only by 30-40% of the population who have the appropriate gut microflora needed to convert dietary precursors into UA. UA has been shown to stimulate mitophagy and improve muscle function in pre-clinical models and to improve mitochondrial health in older adults.

Purpose: To determine the effects of UA supplementation on physical performance and mitochondrial health in middle-aged healthy adults.

Methods: Healthy middle-aged adults (n = 88, between 40-64 years) were randomly assigned to 3 different supplementation groups. Each group was provided with either UA (500 mg/day), UA (1000 mg/day) or a placebo for 4 months. The effect of supplementation was investigated on muscle strength (isokinetic peak torque), physical performance (six-minute walk test), exercise capacity (peak VO2) and biomarkers of mitochondrial health (from muscle biopsies and blood plasma). Long term safety and compliance were also assessed.

Results: The average age of participants in each group was not significantly different; 51 + 7 yrs in UA 500 mg/day group vs. 52 + 6 yrs in UA 1000 mg/day group vs. 54 + 6 yrs in placebo group. Average peak torque in the knee flexors was significantly increased in both UA 500 mg/day (+12.0%, p < 0.05 compared with placebo) and UA 1000 mg/day groups (+9.8%, p < 0.05 compared with placebo). At the highest dose of 1000 mg/day, UA increased peak VO2 (~10%, p = 0.058) compared to placebo. The UA 1000 mg/day group showed a significant increase from baseline in physical performance during the six-minute walk test, with an increased mean distance of 33.43 m (p < 0.05). Muscle proteomics showed UA elevated levels of protein involved in mitophagy and oxidative phosphorylation, markers of improved mitochondrial quality and respiratory capacity. In the plasma, UA reduced acylcarnitines and C-reactive protein levels, indicating higher mitochondrial efficiency and reduced inflammation at the systemic level.

Conclusion: Direct calibrated supplementation with UA is an appealing nutritional strategy to deliver health benefits on muscle function, physical performance, and mitochondrial health.

Source: Singh, Anurag1; Bailey, David M.1; Werner, Emily2. Urolithin A, A Gut Microbiome Derived Compound Improves Mitochondrial Health And Muscle Performance: 335. Medicine & Science in Sports & Exercise 54(9S):p 77, September 2022. | DOI: 10.1249/01.mss.0000875996.82777.91

Orally Administered Urolithin A Is Safe And Modulates Muscle And Mitochondrial Biomarkers In Elderly

Abstract

Background: Age associated muscle and physical decline that leads to frailty and sarcopenia has become a significant public health concern. This has fueled a growing interest to identify novel interventions that can mitigate the process of muscle aging. Urolithin A (UA), is a natural metabolite derived from ellagitannins, compounds found in pomegranates, nuts and berries. UA has been shown to improve mitochondrial function by stimulating mitophagy, resulting in enhanced exercise capacity that was observed in two separate models of age-related decline in muscle function (Nature Medicine 22, 879–888 (2016). Objective: To investigate the safety of UA and its impact on biomarkers in a first-in-human Phase 1 clinical trial in elderly.

Methods: A single center, multi-part (single and 4-week multiple ascending doses) Phase I, double-blind, randomized, placebo controlled study in 60 healthy elderly subjects was conducted (NCT02655393). All of the subjects were between 61 to 85 years of age and sedentary with a BMI range of 18–32 kg/m2. The subjects modified their diet to exclude pomegranates, berries and nuts as well as dietary supplements for the duration of the study. Plasma samples and muscle biopsies from the vastus lateralis muscle were collected to investigate the effects of UA on the plasma metabolomics profile and the skeletal muscle transcriptome..

Results: The primary endpoint of safety was successfully met as no serious or product related non-serious adverse effects were recorded. No clinically significant changes were observed in a battery of safety tests (vital signs, physical examination, ECG, serum biochemistry, haematology and urinalysis), indicating a favourable safety profile for UA in humans. The impact of UA on plasma and muscle biomarkers following a 4-week dosing were assessed, and this revealed that UA modulated both genes and metabolites linked to mitochondrial and muscle function.

Conclusion: UA is well tolerated and has an attractive safety profile when orally administered in single and multiple doses to elderly. Importantly, UA is bioavailable in both human plasma and muscle and modulated biomarkers of muscle and mitochondrial function. Our results hold promise for the use of advanced dietary interventions involving UA to manage mitochondrial and muscle health during aging.

Source: A. Singh, P. Andreux, W. Blanco-Bose, D. Ryu, P. Aebischer, J. Auwerx, C. Rinsch, ORALLY ADMINISTERED UROLITHIN A IS SAFE AND MODULATES MUSCLE AND MITOCHONDRIAL BIOMARKERS IN ELDERLY, Innovation in Aging, Volume 1, Issue suppl_1, July 2017, Pages 1223–1224, https://doi.org/10.1093/geroni/igx004.4446

Urolithin A enhances muscle performance in elderly and positively impacts biomarkers linked to cellular health

Abstract

Background: Aging is associated with decline in mitochondrial function and reduced exercise capacity. Urolithin A (UA) is a natural gut metabolite shown to stimulate mitophagy and improve muscle function in aged animals, and induce mitochondrial gene expression in elderly.

Purpose: Investigate if oral administration of UA improved walking distance (6MWT), muscle fatigue resistance in hand (FDI) and leg (TA) muscles, and had an impact on plasma biomarkers.

Method: We conducted a randomized, double-blind, placebo-controlled study (NCT03283462) in elderly subjects (65-90 yrs.) supplemented daily with 1000mg UA or placebo for 4 months. 128 subjects were screened and 66 randomized. 6MWT and ATPmax via MRS were assessed at baseline and at 4 months. Muscle fatigue tests and plasma analysis of biomarkers were assessed at baseline, 2 and 4 months. Results: UA significantly improved muscle endurance (i.e., change in number of muscle contractions from baseline) in two different muscles (hand: PL 11.6 ±147.5, UA 95.3 ± 115.5; and leg: PL 5.7± 127.1, UA 41.4 ±65.5) compared with placebo at 2-months. Plasma levels of several acylcarnitines, ceramides and C-reactive-protein were decreased by UA at the end-of study. 6MWT distance (PL 42.5 ± 73.3 m, UA 60.8± 67.2 m) and ATPmax increased in both groups from baseline (PL 13.7±31.4%, UA19.4± 56.8%) with UA supplemented group exhibiting greater improvements, although these were not statistically different between groups.

Conclusion: UA supplementation improved muscle endurance, metabolic and inflammatory plasma biomarkers after 2-months, suggesting that UA can have a positive impact on muscle and cellular health in the elderly.

Source: Sophia Liu, David Marcinek, Urolithin A enhances muscle performance in elderly and positively impacts biomarkers linked to cellular health, Innovation in Aging, Volume 5, Issue Supplement_1, 2021, Page 671, https://doi.org/10.1093/geroni/igab046.2529

Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults

Summary

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.

Source: Anurag Singh, Davide D’Amico, Pénélope A. Andreux, Andréane M. Fouassier, William Blanco-Bose, Mal Evans, Patrick Aebischer, Johan Auwerx, Chris Rinsch, Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults, Cell Reports Medicine, Volume 3, Issue 5, 2022, 100633, ISSN 2666-3791, https://doi.org/10.1016/j.xcrm.2022.100633.

Effect of urolithin A on the improvement of vascular endothelial function depends on the gut microbiota

Abstract

Background: Urolithin A (UA) is a metabolite produced by gut microbiota from ingested ellagic acid. Although the effect of ellagic acid intake on vascular endothelial function (VEF) improvement has been reported, the effect of UA intake on VEF improvement remains obscure. In addition, UA has been reported to improve the intestinal barrier function, and UA may have improved VEF by gut microbiome alteration.

Objective: In this study, we conducted a clinical trial to explore and analyze the effects of UA intake on vascular endothelial function (VEF) and characteristics of the intestinal environment, such as gut microbiome profiling and organic acid composition.

Methods: A placebo-controlled, randomized, double-blinded, parallel group trial was conducted on participants who could metabolize small amounts of UA from ellagic acid (non-UA producers) and had relatively poor VEF. VEF was assessed using the flow-mediated vasodilatation (FMD) score. Participants were administered placebo, UA 10 mg/day, or UA 50 mg/day for 12 weeks. FMD was measured and fecal samples were collected at 0, 4, 8, and 12 weeks of treatment. Gut microbiome analysis and organic acid level measurements were performed to evaluate the effects of UA intake on the intestinal environment. This clinical trial is publicly registered at the UMIN-CTR, trial number: UMIN000042014.

Results: The gut microbiota of the UA 50 mg/day group showed a significant increase in alpha diversity (Faith’s phylogenetic diversity). Four and nine microbial genera were significantly altered in the UA 10 mg/day and UA 50 mg/day groups, respectively (p < 0.05, not corrected). Participants whose FMD scores improved with UA intake had poor baseline FMD values as well as a low Bacillota/Bacteroidota ratio.

Conclusion: Urolithin A intake alters the gut microbiota and improves their alpha diversity. In addition, the effect of UA on VEF correlated with the individual gut microbiota. Our results have practical implications for a new approach to providing healthcare that focuses on intestinal environment-based diet therapy.

Source: Nishimoto Y, Fujisawa K, Ukawa Y, Kudoh M, Funahashi K, Kishimoto Y and Fukuda S (2023) Effect of urolithin A on the improvement of vascular endothelial function depends on the gut microbiota. Front. Nutr. 9:1077534. doi: 10.3389/fnut.2022.1077534

Nicotinamide mononucleotide (NMN)

Nicotinamide mononucleotide (NMN) intake increases plasma NMN and insulin levels in healthy subjects

Summary

Introduction: Nicotinamide adenine dinucleotide (NAD+) is a coenzyme of the NAD+-dependent protein deacetylase sirtuin-1 (SIRT1). An increase in NAD+ concentration induces SIRT1 activation that results in various health benefits. Since nicotinamide mononucleotide (NMN) is a precursor of NAD+, NMN ingestion is expected to have multiple health benefits such as alleviation of aging, lifestyle-related and neurodegenerative diseases, through the activation of SIRT1. In this study, we aimed to determine the effects of daily NMN ingestion on plasma levels of NMN and NAD+.

Methods: Healthy volunteers received 250 mg of NMN once a day in the morning (n = 11) for 12 weeks, and the plasma concentrations of NMN and NAD+ were measured monthly. Physiological and laboratory tests were performed within 2 h after lunch (at 2 pm) before and during NMN administration.

Results: Oral administration of NMN increased the plasma concentrations of NMN and NAD+, and the postprandial serum insulin levels. The elevation levels of NMN and insulin varied widely among individuals. No adverse symptoms were observed in the participants.

Conclusions: Oral administration of NMN elevates plasma levels of NMN and NAD+, and postprandial serum insulin levels.

Source: Yamane T, Imai M, Bamba T, Uchiyama S. Nicotinamide mononucleotide (NMN) intake increases plasma NMN and insulin levels in healthy subjects; Clinical Nutrition ESPEN, 2023; 56, 83-86. DOI: 10.1016/j.clnesp.2023.04.031

Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners: a randomized, double-blind study

Abstract

Background: Recent studies in rodents indicate that a combination of exercise training and supplementation with nicotinamide adenine dinucleotide (NAD+) precursors has synergistic effects. However, there are currently no human clinical trials analyzing this.

Objective: This study investigates the effects of a combination of exercise training and supplementation with nicotinamide mononucleotide (NMN), the immediate precursor of NAD+, on cardiovascular fitness in healthy amateur runners.

Methods: A six-week randomized, double-blind, placebo-controlled, four-arm clinical trial including 48 young and middle-aged recreationally trained runners of the Guangzhou Pearl River running team was conducted. The participants were randomized into four groups: the low dosage group (300 mg/day NMN), the medium dosage group (600 mg/day NMN), the high dosage group (1200 mg/day NMN), and the control group (placebo). Each group consisted of ten male participants and two female participants. Each training session was 40–60 min, and the runners trained 5–6 times each week. Cardiopulmonary exercise testing was performed at baseline and after the intervention, at 6 weeks, to assess the aerobic capacity of the runners.

Results: Analysis of covariance of the change from baseline over the 6 week treatment showed that the oxygen uptake (VO2), percentages of maximum oxygen uptake (VO2max), power at first ventilatory threshold, and power at second ventilatory threshold increased to a higher degree in the medium and high dosage groups compared with the control group. However, there was no difference in VO2max, O2-pulse, VO2 related to work rate, and peak power after the 6 week treatment from baseline in any of these groups.

Conclusion: NMN increases the aerobic capacity of humans during exercise training, and the improvement is likely the result of enhanced O2 utilization of the skeletal muscle.

Sources: Jiaqi Zhang, Eric Tsz-Chun Poon & Stephen Heung-Sang Wong. (2025) Efficacy of oral nicotinamide mononucleotide supplementation on glucose and lipid metabolism for adults: a systematic review with meta-analysis on randomized controlled trials. Critical Reviews in Food Science and Nutrition 65:22, pages 4382-4400. DOI: 10.1186/s12970-021-00442-4

The efficacy and safety of β-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial

Abstract

In animal studies, β-nicotinamide mononucleotide (NMN) supplementation increases nicotinamide adenine dinucleotide (NAD) concentrations and improves healthspan and lifespan with great safety. However, it is unclear if these effects can be transferred to humans. This randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial included 80 middle-aged healthy adults being randomized for a 60-day clinical trial with once daily oral dosing of placebo, 300 mg, 600 mg, or 900 mg NMN. The primary objective was to evaluate blood NAD concentration with dose-dependent regimens. The secondary objectives were to assess the safety and tolerability of NMN supplementation, next to the evaluation of clinical efficacy by measuring physical performance (six-minute walking test), blood biological age (Aging.Ai 3.0 calculator), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), and subjective general health assessment [36-Item Short Form Survey Instrument (SF-36)]. Statistical analysis was performed using the Per Protocol analysis with significant level set at p = 0.05. All 80 participants completed the trial without trial protocol violation. Blood NAD concentrations were statistically significantly increased among all NMN-treated groups at day 30 and day 60 when compared to both placebo and baseline (all p ≤ 0.001). Blood NAD concentrations were highest in the groups taking 600 mg and 900 mg NMN. No safety issues, based on monitoring adverse events (AEs), laboratory and clinical measures, were found, and NMN supplementation was well tolerated. Walking distance increase during the six-minute walking test was statistically significantly higher in the 300 mg, 600 mg, and 900 mg groups compared to placebo at both days 30 and 60 (all p < 0.01), with longest walking distances measured in the 600 mg and 900 mg groups. The blood biological age increased significantly in the placebo group and stayed unchanged in all NMN-treated groups at day 60, which resulted in a significant difference between the treated groups and placebo (all p < 0.05). The HOMA-IR showed no statistically significant differences for all NMN-treated groups as compared to placebo at day 60. The change of SF-36 scores at day 30 and day 60 indicated statistically significantly better health of all three treated groups when compared to the placebo group (p < 0.05), except for the SF-36 score change in the 300 mg group at day 30. NMN supplementation increases blood NAD concentrations and is safe and well tolerated with oral dosing up to 900 mg NMN daily. Clinical efficacy expressed by blood NAD concentration and physical performance reaches highest at a dose of 600 mg daily oral intake. This trial was registered with ClinicalTrials.gov, NCT04823260, and Clinical Trial Registry - India, CTRI/2021/03/032421.

Source: Yi, L., Maier, A.B., Tao, R. et al. The efficacy and safety of β-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial. GeroScience 45, 29–43 (2023). https://doi.org/10.1007/s11357-022-00705-1

A single oral supplementation of nicotinamide within the daily tolerable upper level increases blood NAD+ levels in healthy subjects

Abstract

A decrease in nicotinamide adenine dinucleotide (NAD+) levels is a hallmark of aging in multiple species, including humans. Our previous clinical trial showed that supplementation of 200 mg nicotinamide, a form of vitamin B3, increased blood NAD+ levels. Here we report a clinical trial to assess the efficacy of a lower and a higher dose nicotinamide on increasing NAD+ levels. Blood NAD+ levels were evaluated before and after treatment of 100 mg nicotinamide, 500 mg nicotinamide, or water only. The three treatment arms were tested in the same cohort of 5 healthy adults. Oral supplementation of 500 mg nicotinamide led to a significant increase in blood NAD+ after 12 h and showed a trend of increase after 48 h (P = 0.056), whereas 100 mg nicotinamide or water intake only did not change the NAD+ levels in the same subjects. Blood lipidome analysis showed that the levels of 277 lipid species significantly changed after 12 h among 1463 species detected, while no changes were detected at 0 h among the 3 groups. These lipid changes largely reflected the difference between the nicotinamide supplemented groups and the water control group. Together with our previous results, this study shows that oral supplementation of nicotinamide within the daily tolerable upper level is an effective way to transiently increase NAD+ levels and affect the composition of blood lipids.

Source: Takashi K. Ito, Tomohito Sato, Yusuke Takanashi, Zinat Tamannaa, Takuya Kitamoto, Keiichi Odagiri, Mitsutoshi Setou, A single oral supplementation of nicotinamide within the daily tolerable upper level increases blood NAD+ levels in healthy subjects, Translational Medicine of Aging, Volume 5, 2021, Pages 43-51, ISSN 2468-5011, https://doi.org/10.1016/j.tma.2021.09.001.

Nicotinamide mononucleotide: a potential effective natural compound against insulin resistance

Summary

Recently, a study published in Science by Yoshino et al.1 reported on a randomized, placebo-controlled, double-blind clinical trial to examine the effects of a 10-week nicotinamide mononucleotide (NMN) administration on human metabolism in 25 postmenopausal overweight or obese women with prediabetes. It revealed positive effects of NMN on insulin sensitivity, insulin signalling, and tissue remodelling in skeletal muscle.

Source: Roos, J., Zinngrebe, J. & Fischer-Posovszky, P. Nicotinamide mononucleotide: a potential effective natural compound against insulin resistance. Sig Transduct Target Ther 6, 310 (2021). https://doi.org/10.1038/s41392-021-00723-z

Effects of Nicotinamide Mononucleotide Supplementation on Muscle and Liver Functions Among the Middle-aged and Elderly: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Abstract

Introduction: Nicotinamide Mononucleotide (NMN) has gained attention as a precursor to Nicotinamide Adenine Dinucleotide (NAD+) in recent years, commonly utilized in anti-aging therapies. The anti-aging effects of NMN on muscle and liver functions in middleaged and elderly people are still unclear.

Objective: Based on available randomized controlled trials, we conducted a meta-analysis to evaluate the impact of NMN on muscle and liver functions in middle-aged and elderly individuals.

Methods: We conducted searches on three electronic databases (PubMed, Embase, Web of Science) for randomized controlled trials involving NMN interventions in middle-aged and elderly populations. Through the Cochrane Handbook, we assessed the specific methodological quality. All statistical analyses were obtained by Stata15, and statistical significance was set as P<0.05.

Results: There were 412 participants from 9 studies in this meta-analysis. Based on changes in gait speed (SMD: 0.34 m/s, 95%CI [0.03, 0.66] p = 0.033), NMN had significant effects on muscle mass. Moreover, NMN had a better effect on ALT (SMD: -0.29 IU/L, 95%CI [-0.55, -0.03] p = 0.028). Subgroup analysis indicated that administering a small dose of NMN exerted the most prominent impact on Homeostasis Model Assessment-Insulin Resistance (HOMA-IR).

Conclusion: NMN has positive efficacy in enhancing muscle function, reducing insulin resistance and lowering aminotransferase levels in middle-aged and elderly individuals. NMN is an encouraging and considerable drug for anti-aging treatment.

Source: Wang J, Wang L, Wang T, Zhang Y, Zhou A, Wang Z, Xiong Z. Effects of Nicotinamide Mononucleotide Supplementation on Muscle and Liver Functions Among the Middle-aged and Elderly: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Volume 26, Issue 13, 2025, Published on: 23 August, 2024, Page: [2141 - 2152], Pages: 12, DOI: 10.2174/0113892010306242240808094303

Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women

Synthesis of nicotinamide adenine dinucleotide (NAD+) decreases during aging, which is thought to limit the activity of enzymes that require it for their catalytic activity. Studies in animals indicate that replenishment of cellular NAD+ can have beneficial effects on aging and age-related diseases, but the situation in humans is less clear. Yoshino et al. report the effects of supplementation with the NAD+ precursor nicotinamide mononucleotide in overweight or obese postmenopausal women with prediabetes (see the Perspective by Hepler and Bass). The treatment improved insulin sensitivity in muscle, although a change in NAD+ content was not detected. The treatment also increased the expression of platelet-derived growth factor b. The results support potential therapeutic action of NAD+ supplementation in humans, but how various NAD+ precursors are processed in specific tissues remains to be fully explored.

Source: Mihoko Yoshino et al., Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science 372,1224-1229(2021). DOI:10.1126/science.abe9985

The efficacy and safety of β-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial

Abstract

Source: Yi L, Maier AB, Tao R, Lin Z, Vaidya A, Pendse S, Thasma S, Andhalkar N, Avhad G, Kumbhar V. The efficacy and safety of β-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial. Geroscience. 2023 Feb;45(1):29-43. doi: 10.1007/s11357-022-00705-1. Epub 2022 Dec 8. PMID: 36482258; PMCID: PMC9735188.

Chronic nicotinamide mononucleotide supplementation elevates blood nicotinamide adenine dinucleotide levels and alters muscle function in healthy older men

Abstract

Preclinical studies have revealed that the elevation of nicotinamide adenine dinucleotide (NAD + ) upon the administration of nicotinamide mononucleotide (NMN), an NAD + precursor, can mitigate aging-related disorders; however, human data on this are limited. We investigated whether the chronic oral supplementation of NMN can elevate blood NAD + levels and alter physiological dysfunctions in healthy older participants. We administered 250 mg NMN per day to aged men for 6 or 12 weeks in a placebo-controlled, randomized, double-blind, parallel-group trial. Chronic NMN supplementation was well tolerated and caused no significant deleterious effect. Metabolomic analysis of whole blood samples demonstrated that oral NMN supplementation significantly increased the NAD + and NAD + metabolite concentrations. There were nominally significant improvements in gait speed and performance in the left grip test, which should be validated in larger studies; however, NMN exerted no significant effect on body composition. Therefore, chronic oral NMN supplementation can be an efficient NAD + booster for preventing aging-related muscle dysfunctions in humans.

Source: Igarashi, M., Nakagawa-Nagahama, Y., Miura, M. et al. Chronic nicotinamide mononucleotide supplementation elevates blood nicotinamide adenine dinucleotide levels and alters muscle function in healthy older men. npj Aging 8, 5 (2022). https://doi.org/10.1038/s41514-022-00084-z

Resveratrol

A Resveratrol and Polyphenol Preparation Suppresses Oxidative and Inflammatory Stress Response to a High-Fat, High-Carbohydrate Meal

A supplement containing resveratrol and muscadine polyphenols prior to a high-fat high-carbohydrate meal significantly reduced multiple indices of oxidative and inflammatory stress.

Abstract

Background: High-fat, high-carbohydrate (HFHC) meals are known to induce oxidative and inflammatory stress, an increase in plasma endotoxin concentrations, and an increase in the expression of suppressor of cytokine signaling-3 (SOCS-3).

Hypothesis: The intake of a nutritional supplement containing resveratrol and muscadine grape polyphenols reduces HFHC meal-induced oxidative and inflammatory stress and stimulates the activity of the antioxidant transcription factor, NF-E2-related factor-2 (Nrf-2), and its downstream targets.

Methods: Ten normal, healthy subjects were given a 930-kcal HFHC meal either with placebo or with the supplement. Indices of oxidative stress, inflammation, Nrf-2 binding activity, the concentrations of endotoxin (lipopolysaccharide) and lipoprotein binding protein (LBP), and the expression of toll-like receptor 4 (TLR-4), CD14, IL-1β, TNFα, SOCS-3, Keap-1, NAD(P)H:quinone oxidoreductase-1 (NQO-1), and GST-P1 were measured.

Results: The intake of the supplement suppressed the meal-induced elevations of plasma endotoxin and LBP concentrations, the expression of p47phox, TLR-4, CD14, SOCS-3, IL-1β, and Keap-1, while enhancing Nrf-2 binding activity and the expression of NQO-1 and GST-P1 genes.

Conclusion: A supplement containing resveratrol and muscadine polyphenols suppresses the increase in oxidative stress, lipopolysaccharide and LBP concentrations, and expression of TLR-4, CD14, IL-1β and SOCS-3 in mononuclear cells after an HFHC meal. It also stimulates specific Nrf-2 activity and induces the expression of the related antioxidant genes, NQO-1 and GST-P1. These results demonstrate the acute antioxidant and antiinflammatory effects of resveratrol and polyphenolic compounds in humans in the postprandial state.

Source: Ghanim H, Sia CL, Korzeniewski K, Lohano T, Abuaysheh S, Marumganti A, Chaudhuri A, Dandona P. A resveratrol and polyphenol preparation suppresses oxidative and inflammatory stress response to a high-fat, high-carbohydrate meal. J Clin Endocrinol Metab. 2011 May;96(5):1409-14. doi: 10.1210/jc.2010-1812. Epub 2011 Feb 2. PMID: 21289251; PMCID: PMC3085195.

Resveratrol supplementation reduces ACE2 expression in human adipose tissue

Abstract

Angiotensin converting enzyme-2 (ACE2) is the cell-surface receptor enabling cellular entry of SARS-CoV-2. ACE2 is highly expressed in adipose tissue (AT), rendering AT a potential SARS-CoV-2 reservoir contributing to massive viral spread in COVID-19 patients with obesity. Although rodent and cell studies suggest that the polyphenol resveratrol alters ACE2, human studies are lacking. Here, we investigated the effects of 30-days resveratrol supplementation on RAS components in AT and skeletal muscle in men with obesity in a placebo-controlled cross-over study. Resveratrol markedly decreased ACE2 (~40%) and leptin (~30%), but did neither alter angiotensinogen, ACE and AT1R expression in AT nor skeletal muscle RAS components. These findings demonstrate that resveratrol supplementation reduces ACE2 in AT, which might dampen SARS-CoV-2 spread in COVID-19.

Source: de Ligt M, Hesselink MKC, Jorgensen J, Hoebers N, Blaak EE, Goossens GH. Resveratrol supplementation reduces ACE2 expression in human adipose tissue. Adipocyte. 2021 Dec;10(1):408-411. doi: 10.1080/21623945.2021.1965315. PMID: 34402717; PMCID: PMC8381800.

The protective effects of resveratrol on social stress-induced cytokine release and depressive-like behavior

Abstract

Social stress is a risk factor for psychiatric disorders, however only a subset of the population is susceptible while others remain resilient. Inflammation has been linked to the pathogenesis of psychosocial disorders in humans and may underlie these individual differences. Using a resident-intruder paradigm capable of revealing individual differences in coping behavior and inflammatory responses, the present study determined if resveratrol (RSV; 0, 10, 30mg/kg/day) protected against persistent stress-induced inflammation in socially defeated rats. Furthermore, the antidepressant efficacy of RSV was evaluated using the sucrose preference test. Active coping rats were characterized by more time spent in upright postures and increased defeat latencies versus passive coping rats. Five days after defeat, flow cytometry revealed enhanced stimulation of proinflammatory proteins (IL-β, TNF-α) in spleen cells of passive rats as compared to active coping and controls, an effect that was blocked by both doses of RSV. Furthermore, only passive coping rats exhibited increased proinflammatory proteins (IL-1β, TNF-α, GM-CSF) in the locus coeruleus (LC), a noradrenergic brain region implicated in depression. Notably, only 30mg/kg RSV blocked LC neuroinflammation and importantly, was the only dose that blocked anhedonia. Alternatively, while stress had minimal impact on resting cytokines in the dorsal raphe (DR), RSV dose-dependently reduced DR cytokine expression. However, this did not result in changes in indoleamine 2,3-dioxygenase activity or serotonin levels. Taken together, these data suggest that social stress-induced depressive-like behavior evident in passive coping rats may be driven by stress-induced neuroinflammation and highlight natural anti-inflammatory agents to protect against social stress-related consequences.

Source: Finnell JE, Lombard CM, Melson MN, Singh NP, Nagarkatti M, Nagarkatti P, Fadel JR, Wood CS, Wood SK. The protective effects of resveratrol on social stress-induced cytokine release and depressive-like behavior. Brain Behav Immun. 2017 Jan;59:147-157. doi: 10.1016/j.bbi.2016.08.019. Epub 2016 Aug 31. PMID: 27592314; PMCID: PMC5154920.

Antioxidative Stress Mechanisms behind Resveratrol: A Multidimensional Analysis

Abstract

Over the past decade, oxidative stress was shown to be a key factor for various diseases. The term “antioxidant” also rapidly gained attention worldwide, viewed as beneficial in disease prevention. Resveratrol (RSV), a natural polyphenol, is a plant antitoxin formed in response to harmful environmental factors such as infection and injury. This antitoxin is found in grapes, strawberries, peanuts, or herbal medicines and exhibits many pharmacological effects involved in antitumor, anti-inflammatory, antiaging, and antioxidation stress mechanisms. Recently, numerous in vitro and in vivo experiments have shown that RSV harbors antioxidative stress properties and can be used as an antioxidant. Here, we review the free radical scavenging ability, antioxidant properties, signaling pathways, expression and regulation of antioxidant enzymes, and oxidative stress-related diseases associated with RSV.

Source: Gu, Tongyu, Wang, Nianmin, Wu, Tong, Ge, Qi, Chen, Liang, Antioxidative Stress Mechanisms behind Resveratrol: A Multidimensional Analysis, Journal of Food Quality, 2021, 5571733, 12 pages, 2021. https://doi.org/10.1155/2021/5571733

Resveratrol ameliorates physical and psychological stress-induced depressive-like behavior

Abstract

Objectives: Depression is a mental disorder that profoundly affects all aspects of life, but currently, antidepressants have some problems with their effectiveness and side effects. Resveratrol is a compound that has the ability to regulate the hypothalamic-pituitary-adrenal axis. This study aimed to determine resveratrol's effect on physical and psychological stress-induced depressive-like behavior.

Methods: Mice were divided into control, physical stress, psychological stress groups. Treatment was conducted with fluvoxamine 20 mg/kg and resveratrol 20, 40, and 80 mg/kg for seven days. The depressive-like state was evaluated using a forced swim test (FST), tail suspension test (TST), and open field test (OFT).

Results: Physical stress and psychological stress induction increase the immobility time on FST and TST. Besides, there is an increase in time in central on OFT, which indicates an anxiety or mental illness-like behavior. However, the OFT examination on sniffing, rearing, grooming, and crossing behavior did not show a significant difference. Resveratrol 80 mg/kg and fluvoxamine 20 mg/kg were significantly reduced immobility time at TST compared to the physical stress group. While in psychological stress, resveratrol 80 mg/kg tended to decrease immobility time but not significant. A significant increase in time in central duration was seen in the resveratrol 40 mg/kg compared to the psychological stress. Stress induction causes increased amygdala corticotrophin-releasing factor (CRF) mRNA expression. However, neither resveratrol nor fluvoxamine affected amygdala CRF mRNA expression.

Conclusions: Resveratrol ameliorates depressive-like behavior induced by physical and psychological stress.

Source: Ardianto, Chrismawan & Budiatin, Aniek & Sumartha, Budi & Nurrahmi, Nurrahmi & Rahmadi, Mahardian & Khotib, Junaidi. (2021). Resveratrol ameliorates physical and psychological stress-induced depressive-like behavior. Journal of basic and clinical physiology and pharmacology. 32. 335-340. 10.1515/jbcpp-2020-0437.

Cellular Longevity Complex

CLINICAL STUDIES ON THE FOLLOWING INGREDIENTS:

Urolithin A

Urolithin A, A Gut Microbiome Derived Compound Improves Mitochondrial Health And Muscle Performance

Abstract

Orally Administered Urolithin A Is Safe And Modulates Muscle And Mitochondrial Biomarkers In Elderly

Abstract

Urolithin A enhances muscle performance in elderly and positively impacts biomarkers linked to cellular health

Abstract

Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults

Summary

Effect of urolithin A on the improvement of vascular endothelial function depends on the gut microbiota

Abstract

Nicotinamide mononucleotide (NMN)

Nicotinamide mononucleotide (NMN) intake increases plasma NMN and insulin levels in healthy subjects

Summary

Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners: a randomized, double-blind study

Abstract

The efficacy and safety of β-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial

Abstract

A single oral supplementation of nicotinamide within the daily tolerable upper level increases blood NAD+ levels in healthy subjects

Abstract

Nicotinamide mononucleotide: a potential effective natural compound against insulin resistance

Summary

Effects of Nicotinamide Mononucleotide Supplementation on Muscle and Liver Functions Among the Middle-aged and Elderly: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Abstract

Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women

The efficacy and safety of β-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial

Abstract

Chronic nicotinamide mononucleotide supplementation elevates blood nicotinamide adenine dinucleotide levels and alters muscle function in healthy older men

Abstract

Resveratrol

A Resveratrol and Polyphenol Preparation Suppresses Oxidative and Inflammatory Stress Response to a High-Fat, High-Carbohydrate Meal

Abstract

Resveratrol supplementation reduces ACE2 expression in human adipose tissue

Abstract

The protective effects of resveratrol on social stress-induced cytokine release and depressive-like behavior

Abstract

Antioxidative Stress Mechanisms behind Resveratrol: A Multidimensional Analysis

Abstract

Resveratrol ameliorates physical and psychological stress-induced depressive-like behavior

Abstract

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