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.

Nicotinamide Mononucleotide (NMN);NAD⁺ Activation Stack (NMN + Resveratrol + Pterostilbene);All-in-One Longevity Formulation

Daily NMN supplementation up to 900 mg is safe and increases NAD levels, physical performance, and subjective health in middle-aged adults, with 600 mg showing the highest efficacy.

Can β-nicotinamide mononucleotide (NMN) supplementation increase NAD concentrations and improve health in middle-aged healthy adults, and what are its safety and efficacy at different doses?

Hypothesis: NMN supplementation will increase NAD concentrations and improve healthspan parameters in humans, similar to findings in animal studies, and will be safe and well-tolerated.

This was a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial. 80 healthy middle-aged adults were randomized to receive daily oral doses of placebo, 300 mg, 600 mg, or 900 mg NMN for 60 days. Blood NAD concentration was the primary outcome, while secondary outcomes included safety, tolerability, physical performance (six-minute walking test), blood biological age, HOMA-IR, and subjective general health (SF-36).

Blood NAD concentrations significantly increased in all NMN-treated groups at days 30 and 60 compared to placebo and baseline, with the highest concentrations in the 600 mg and 900 mg groups. No safety issues were observed, and NMN was well tolerated. Walking distance significantly increased in all NMN groups compared to placebo, with the longest distances in the 600 mg and 900 mg groups. Blood biological age increased in the placebo group but remained unchanged in NMN groups. HOMA-IR showed no significant differences, while SF-36 scores indicated significantly better health in all NMN groups compared to placebo.

NMN supplementation increases blood NAD concentrations and is safe and well tolerated at oral doses up to 900 mg daily in healthy middle-aged adults. Clinical efficacy, including improvements in physical performance and subjective health, appears highest at a dose of 600 mg daily.

The abstract does not explicitly state any limitations of the study.


The Safety and Antiaging Effects of Nicotinamide Mononucleotide in Human Clinical Trials: an Update.

Nicotinamide Mononucleotide (NMN);Intracellular NAD⁺ & Longevity Marker Testing

While NMN shows promise in animal and cell studies for antiaging, human clinical trial data is still largely pending.

What are the safety and antiaging effects of nicotinamide mononucleotide (NMN) in human clinical trials?

Hypothesis: NMN supplementation, by increasing NAD concentration, could mitigate aging-related disorders such as oxidative stress, DNA damage, neurodegeneration, and inflammatory responses in humans, similar to findings in cell and animal models.

This is a review article summarizing the current progress of human clinical trials investigating NMN supplementation and its effects, along with an overview of NMN/NAD biology.

The review notes that a dozen human clinical trials with NMN supplementation are currently underway. It highlights that in vitro/in vivo studies have demonstrated NMN supplementation increases NAD concentration and could mitigate aging-related disorders.

The review aims to clarify the potential effects of NMN supplementation and suggest future study directions, acknowledging that most existing evidence comes from cell or animal models, with human trial results still emerging.

Most studies evaluating the effects of NMN have been conducted in cell or animal models, leading to a concern regarding the safety and physiological effects of NMN supplementation in the human population.


Caloric restriction, resveratrol and melatonin: Role of SIRT1 and implications for aging and related-diseases

Nicotinamide Mononucleotide (NMN);NAD⁺ Activation Stack (NMN + Resveratrol + Pterostilbene);Trans-Resveratrol;All-in-One Longevity Formulation;Polyphenol Antioxidant Blend

Caloric restriction, resveratrol, and melatonin may combat aging and age-related diseases by activating sirtuins and scavenging free radicals.

What roles do caloric restriction, resveratrol, and melatonin play in aging and age-related diseases, particularly concerning sirtuin 1 (SIRT1) activation?

Hypothesis: Free radicals contribute to aging through oxidative damage, but also modulate signaling pathways like those related to sirtuins. Caloric restriction extends lifespan by inducing sirtuins. Resveratrol and melatonin, both sirtuin activators and free radical scavengers, may offer synergistic benefits for health and longevity.

This abstract is a review and does not describe specific experimental methods. It synthesizes existing research on caloric restriction, resveratrol, and melatonin.

Caloric restriction extends lifespan and improves healthspan, partly by inducing sirtuins. Resveratrol, a polyphenol, has antioxidant, antifungal, and sirtuin-activating properties. Melatonin, an endogenous free radical scavenger that declines with age, also activates sirtuins and has anti-inflammatory and circadian rhythm regulatory functions. Both melatonin and resveratrol are present in foods and may have synergistic effects.

Caloric restriction, resveratrol, and melatonin are implicated in modulating aging processes, partly through their effects on sirtuins, particularly SIRT1. Their presence in diet and potential synergistic actions suggest they could promote health and longevity.

This abstract does not present new experimental data or discuss specific limitations of the reviewed studies. It is a conceptual overview.


The Potential of Resveratrol to Act as a Caloric Restriction Mimetic Appears to Be Limited: Insights from Studies in Mice

NAD⁺ Activation Stack (NMN + Resveratrol + Pterostilbene);Trans-Resveratrol

Resveratrol's ability to mimic caloric restriction and provide significant health benefits in mice is largely unproven and inconsistent across studies.

Can resveratrol (RSV) mimic the effects of caloric restriction (CR) in mice to counteract age- and obesity-related diseases?

Hypothesis: It has been hypothesized that resveratrol (RSV) may counteract age- and obesity-related diseases similarly to caloric restriction (CR), potentially by activating molecular targets like SIRT1, AMPK, and PPARGC1A.

The authors conducted a systematic literature search on PubMed (on April 15, 2020) to identify trials that directly compared resveratrol (RSV) application to caloric restriction (CR) feeding in mice.

In most studies identified, mice supplemented with resveratrol (RSV) did not show significant reductions in body weight, glucose, or insulin. Some studies also reported that RSV and caloric restriction (CR) treatments affected molecular targets differently, and findings on their impacts varied between trials. While there might be a moderate effect of RSV on insulin sensitivity, data are inconsistent.

Current evidence does not fully support the use of resveratrol (RSV) to prevent or treat age- or obesity-related diseases, although it may moderately mimic some aspects of caloric restriction (CR) under certain circumstances.

The abstract notes that findings on resveratrol's effects vary between trials and that data are inconsistent, indicating a lack of clear, reproducible results across studies.


Cardioprotection and lifespan extension by the natural polyamine spermidine.

Spermidine supplementation improves heart health and extends lifespan in animal models, and higher dietary intake is linked to better cardiovascular outcomes in humans.

Can oral spermidine supplementation extend lifespan and provide cardioprotection in aging mice and rats, and is there a correlation with cardiovascular health in humans?

Hypothesis: The study hypothesized that oral spermidine supplementation would extend lifespan and exert cardioprotective effects by improving cardiac function and reducing hypertrophy, potentially through mechanisms involving autophagy and titin phosphorylation.

The study involved oral spermidine supplementation in mice to assess lifespan, cardiac hypertrophy, and diastolic function. Cardiac autophagy, mitophagy, mitochondrial respiration, and cardiomyocyte mechano-elastical properties were also examined, along with titin phosphorylation and inflammation. Mice lacking Atg5 in cardiomyocytes were used to investigate the role of autophagy. Dahl salt-sensitive rats on a high-salt diet were used to model hypertension-induced congestive heart failure, with spermidine feeding assessed for effects on blood pressure, hypertrophy, and diastolic function. In humans, dietary spermidine levels were assessed via food questionnaires and correlated with blood pressure and cardiovascular disease incidence.

Oral spermidine supplementation extended the lifespan of mice, reduced cardiac hypertrophy, and preserved diastolic function in old mice. It enhanced cardiac autophagy, mitophagy, mitochondrial respiration, and improved cardiomyocyte mechano-elastical properties, coinciding with increased titin phosphorylation and suppressed subclinical inflammation. Cardioprotection was not observed in mice lacking Atg5 in cardiomyocytes. In Dahl salt-sensitive rats, spermidine feeding reduced systemic blood pressure, increased titin phosphorylation, and prevented cardiac hypertrophy and diastolic dysfunction, delaying heart failure progression. In humans, high dietary spermidine levels correlated with reduced blood pressure and a lower incidence of cardiovascular disease.

Oral spermidine supplementation extends lifespan and provides cardioprotection in mice and rats, likely through mechanisms involving autophagy and titin phosphorylation. Higher dietary spermidine intake in humans is associated with better cardiovascular health.

The human data relies on correlations from food questionnaires, which may not establish causality. The study did not specify the exact doses of spermidine used in animal models or the specific dietary intake levels in humans.


Induction of autophagy by spermidine promotes longevity.

Spermidine (Wheat-Germ Extract);All-in-One Longevity Formulation;Cellular Senescence & Inflammation Panel

Spermidine extends lifespan and reduces oxidative stress by triggering autophagy through epigenetic changes in various organisms and human cells.

Does spermidine administration affect the lifespan of various organisms and human cells?

Hypothesis: The study investigates whether spermidine, a natural polyamine, can extend lifespan and inhibit oxidative stress by inducing autophagy.

Spermidine was administered to yeast, flies, worms, and human immune cells to observe its effect on lifespan. Its impact on oxidative stress was assessed in ageing mice. The study also examined the epigenetic effects of spermidine on histone H3 acetylation and the expression of autophagy-related transcripts in yeast, flies, worms, and human cells. The role of autophagy in polyamine-induced longevity was also investigated.

Spermidine administration significantly extended the lifespan of yeast, flies, worms, and human immune cells. It also potently inhibited oxidative stress in ageing mice. In ageing yeast, spermidine treatment inhibited histone acetyltransferases (HAT), leading to epigenetic deacetylation of histone H3, which suppressed oxidative stress and necrosis. Depletion of endogenous polyamines resulted in hyperacetylation, increased reactive oxygen species, early necrotic death, and reduced lifespan. The altered chromatin acetylation status led to significant upregulation of autophagy-related transcripts, inducing autophagy in yeast, flies, worms, and human cells. Enhanced autophagy was found to be crucial for polyamine-induced suppression of necrosis and increased longevity.

Spermidine administration promotes longevity across multiple species and in human cells by inducing autophagy, which is mediated by epigenetic deacetylation of histone H3 and suppression of oxidative stress and necrosis.


Krebs cycle intermediates regulate DNA and histone methylation: epigenetic impact on the aging process

Calcium Alpha-Ketoglutarate (Ca-AKG);All-in-One Longevity Formulation;Methylation & MTHFR Genetic Testing

Krebs cycle intermediates influence DNA and histone methylation, suggesting a link between metabolism, epigenetics, and aging.

How do Krebs cycle intermediates regulate DNA and histone methylation, and what is their epigenetic impact on the aging process?

Hypothesis: Age-related disturbances in Krebs cycle function induce stochastic epigenetic changes in chromatin structures, which promote the aging process.

This study is a review of existing literature concerning the epigenetic mechanisms by which Krebs cycle intermediates control DNA and histone methylation.

Krebs cycle intermediates can shape the epigenetic landscape of chromatin by regulating DNA and histone methylation. Specifically, 2-oxoglutarate (α-ketoglutarate) is an obligatory substrate for 2-oxoglutarate-dependent dioxygenases (2-OGDO), which include major enzymes for DNA and histone demethylation (TETs and JmjC demethylases). Conversely, succinate and fumarate, also Krebs cycle intermediates, are potent inhibitors of 2-OGDO enzymes. This balance of Krebs cycle reactions can affect the level of DNA and histone methylation and thus control gene expression.

Krebs cycle intermediates regulate DNA and histone methylation through their involvement with 2-oxoglutarate-dependent dioxygenases. Disturbances in Krebs cycle function may lead to epigenetic changes that contribute to the aging process.

This is a review article and does not present new experimental data. The proposed link between age-related Krebs cycle disturbances and stochastic epigenetic changes is a hypothesis based on existing evidence.


Alpha-Ketoglutarate dietary supplementation to improve health in humans

Calcium Alpha-Ketoglutarate (Ca-AKG);All-in-One Longevity Formulation

Alpha-ketoglutarate shows promise in animal studies for healthspan extension, but more recent human research is needed to confirm its benefits for aging and age-related diseases.

Can alpha-ketoglutarate (AKG) dietary supplementation improve health and treat age-related diseases in humans?

Hypothesis: The pleiotropic functions of AKG, including its roles as an antioxidant and in metabolic, epigenetic, and immune regulation, suggest it may extend human healthspan and treat age-related diseases.

This is a review article discussing the regulatory role of AKG in aging and its potential therapeutic use in humans. It references past studies in worms, mice, and a few human studies from the 1980s and 1990s.

Recent studies in worms and mice support the concept that AKG may extend healthspan. Older human studies suggested potential benefits of AKG in muscle growth, wound healing, and faster post-surgery recovery. However, there are no recently published human studies demonstrating AKG's role in treating aging and age-related diseases.

While AKG shows promise in animal models and older human studies suggested some benefits, further clinical studies are required to better understand its role in treating aging and age-related diseases in humans.

There is a lack of recently published human studies demonstrating the role of AKG in treating aging and age-related diseases.


The effect of Berberine on weight loss in order to prevent obesity: A systematic review

Berberine shows promise for obesity prevention and treatment by influencing gut bacteria, glucose, and fat metabolism.

What is the effect of Berberine on weight loss and obesity prevention?

Hypothesis: Berberine may be effective in managing obesity and its related metabolic consequences.

This systematic review critically overviewed experimental studies (in vitro, human, and animal) that evaluated Berberine's efficacy in obesity management and its metabolic effects.

In preclinical models, Berberine affected gut microbiota (reducing diversity at 100 mg/kg/day), inhibited α-glycosidase (200 mg/kg/day), and decreased adipocyte differentiation (150 mg/kg/day). It also inhibited hepatic gluconeogenesis and, when associated with Red Yeast Rice, decreased lipid levels in rats (40-380 mg/kg/day). Human studies confirmed gut microbe modulation (500 mg/day), beneficial impact on cholesterol absorption gene regulation (300 mg/day), and amelioration of glucose accumulation (1.0 g/day).

Berberine demonstrates an impact on obesity treatment and prevention through various mechanisms, including effects on gut microbiota, glucose metabolism, adipocyte differentiation, and lipid levels, as supported by both preclinical and human studies.

The abstract does not explicitly state any limitations of the systematic review itself.


Association between vitamin D supplementation and mortality: systematic review and meta-analysis

Vitamin D3 (Cholecalciferol);Targeted Organ-Support Nutrients;Smart Body-Composition Analysis

Vitamin D supplementation did not reduce overall mortality but was associated with a 16% reduction in cancer-related deaths.

Is vitamin D supplementation associated with lower mortality in adults?

Hypothesis: The study aimed to investigate if vitamin D supplementation is associated with lower mortality.

This systematic review and meta-analysis included 52 randomized controlled trials with 75,454 participants. The trials compared vitamin D supplementation to placebo or no treatment for mortality outcomes. Data extraction and quality assessment were conducted independently, and meta-analyses used fixed and random effects models to calculate risk ratios for death.

Vitamin D supplementation was not associated with all-cause mortality (risk ratio 0.98), cardiovascular mortality (0.98), or non-cancer, non-cardiovascular mortality (1.05). However, vitamin D supplementation significantly reduced the risk of cancer death (0.84). Subgroup analyses showed all-cause mortality was significantly lower in trials with vitamin D supplementation, but neither vitamin D nor vitamin D alone significantly reduced all-cause mortality.

Vitamin D supplementation alone was not associated with a reduction in all-cause mortality in adults. However, vitamin D supplementation was found to reduce the risk of cancer death by 16%.

The abstract does not explicitly state limitations of the study beyond the need for additional large clinical studies.


Daily oral supplementation with collagen peptides combined with vitamins improves skin elasticity and has a beneficial effect on joint and general wellbeing

A daily supplement with collagen peptides and other nutrients improved skin elasticity and joint health in a 90-day study.

Can daily oral supplementation with a liquid nutraceutical containing hydrolyzed fish collagen, vitamins, antioxidants, and other active ingredients improve skin texture and elasticity, and protect joint health?

Hypothesis: Daily oral supplementation with a liquid nutraceutical containing hydrolyzed fish collagen, vitamins, antioxidants, and other active ingredients could improve skin texture and elasticity, and have a protective effect on joint health.

A double-blind, randomized, placebo-controlled clinical trial was conducted over 90 days. 120 subjects were randomized to consume either the test product or a placebo daily. Skin elasticity was measured, and histological analysis of skin biopsies was performed. Self-perception questionnaires were used to assess skin hydration, elasticity, joint pain, and joint mobility.

Subjects consuming the test product showed a significant increase in skin elasticity (+40%) compared to placebo. Histological analysis revealed positive changes in skin architecture, including reduced solar elastosis and improved collagen fiber organization. Self-perception questionnaires confirmed subjects' perceptions of more hydrated and elastic skin. The test product also reduced joint pain by -43% and improved joint mobility by +39%.

Oral supplementation with collagen bioactive peptides combined with chondroitin sulphate, glucosamine, L-carnitine, vitamins, and minerals significantly improved clinical parameters related to skin aging and joint health.


Collagen supplementation in skin and orthopedic diseases: A review of the literature

Collagen supplementation may improve skin elasticity and hydration, reduce wrinkles, and enhance bone and joint health.

What are the beneficial effects of collagen consumption in the treatment of skin and orthopedic diseases?

Hypothesis: The study hypothesized that collagen supplementation would show beneficial effects on skin and orthopedic health.

This study was a literature review, synthesizing existing scientific evidence on the effects of collagen consumption.

Collagen supplementation was found to decrease wrinkle formation, increase skin elasticity, hydration, and collagen content, density, and synthesis. For orthopedic health, it increased bone strength, density, and mass, improved joint stiffness/mobility and functionality, and reduced pain.

Collagen supplementation demonstrates potential benefits for both skin and orthopedic health, addressing aging-related damage and issues from physical activity.

The abstract does not explicitly state any limitations of the review itself or the body of literature it synthesized.


Supplementing Glycine and N-Acetylcysteine (GlyNAC) in Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, and Aging Hallmarks: A Randomized Clinical Trial

All-in-One Longevity Formulation;Targeted Organ-Support Nutrients;Polyphenol Antioxidant Blend;Glutathione;Cellular Senescence & Inflammation Panel;Glycan-Based Inflammatory Age Testing;At-Home Food & Allergen Testing;Glycine Powder;GlyNAC (Glycine + N-Acetylcysteine)

GlyNAC supplementation in older adults can improve several age-related health issues, including glutathione deficiency, oxidative stress, and physical function.

Can GlyNAC supplementation improve glutathione deficiency, oxidative stress, mitochondrial dysfunction, insulin resistance, physical function, and aging hallmarks in older adults?

Hypothesis: Supplementing GlyNAC in older adults will improve glutathione deficiency, oxidative stress, mitochondrial dysfunction, insulin resistance, physical function, and aging hallmarks, similar to observations in aged mice.

A placebo-controlled randomized clinical trial was conducted with 24 older adults (OA) and 12 young adults (YA). OA were randomized to receive either GlyNAC (N=12) or an isonitrogenous alanine placebo (N=12) for 16 weeks. YA (N=12) received GlyNAC for 2 weeks. Participants were assessed before, after 2 weeks, and after 16 weeks for GSH concentrations, oxidative stress, mitochondrial function, inflammation, insulin resistance, physical function, and aging hallmarks.

Compared to young adults, older adults exhibited glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, insulin resistance, multiple aging hallmarks, and impaired physical function. GlyNAC supplementation in older adults, but not placebo, improved or corrected these observed defects.

GlyNAC supplementation for 16 weeks in older adults was safe, well-tolerated, and effectively improved and reversed multiple age-associated abnormalities, suggesting it can promote health in aging humans.


Telomere Length and All-Cause Mortality: A Meta-analysis

Telomere Support;Epigenetic Age (DNA-Methylation Clock) Testing

Shorter telomere length is linked to a higher risk of death from all causes, though the strength of this link varies with age and measurement methods.

Is there an association between telomere length and all-cause mortality?

Hypothesis: The study implicitly hypothesizes that shorter telomere length is associated with increased all-cause mortality risk, given the known association of telomere attrition with age-related diseases.

A meta-analysis was conducted using 25 cohort studies, including four unpublished cohorts from the Swedish Twin Registry (STR) and 21 published studies. The analysis included 12,083 individuals with 2517 deaths from STR studies and a total of 121,749 individuals with 21,763 deaths across all eligible studies. The association between telomere length and all-cause mortality risk was assessed, including stratified analyses by age.

In STR studies, a one standard deviation decrement in leukocyte telomere length corresponded to a 13% increased all-cause mortality risk. Individuals in the shortest telomere length quarter had a 44% higher hazard than those in the longest quarter. Across all eligible studies, a one standard deviation telomere length decrement was associated with a hazard ratio of 1.09. Individuals in the shortest telomere length quarter had a 26% higher hazard compared to the longest quarter. The hazard ratio was smaller in individuals over 80 years old.

Short telomeres are associated with an increased risk of all-cause mortality in the general population. However, heterogeneity in effect estimation was observed, which may be influenced by telomere length measurement techniques and age at measurement.

The study noted between-study heterogeneity in the meta-analysis, and suggested that telomere length measurement techniques and age at measurement contribute to this heterogeneity.


An epigenetic biomarker of aging for lifespan and healthspan

Epigenetic Age (DNA-Methylation Clock) Testing;Comprehensive Blood-Biomarker Testing;Intracellular NAD⁺ & Longevity Marker Testing;Methylation & MTHFR Genetic Testing;Optical Biomarker Scanning

A new epigenetic biomarker, DNAm PhenoAge, is a more accurate predictor of various aging-related health outcomes than previous methods.

Can a new epigenetic biomarker of aging, developed using composite clinical measures of phenotypic age, more accurately predict lifespan and healthspan outcomes compared to existing biomarkers?

Hypothesis: Incorporating composite clinical measures of phenotypic age, which capture differences in lifespan and healthspan, will identify novel CpGs and lead to a more powerful epigenetic biomarker of aging than those developed using chronological age alone.

The researchers developed a new epigenetic biomarker, DNAm PhenoAge, using an innovative two-step process. This biomarker was developed using data from whole blood. They then tested its correlation with age in various tissues and cells and performed an in-depth transcriptional analysis in sorted cells to understand associated pathways.

DNAm PhenoAge strongly outperformed previous measures in predicting various aging outcomes, including all-cause mortality, cancers, healthspan, physical functioning, and Alzheimer's disease. This biomarker correlated strongly with age in every tissue and cell tested. Increased epigenetic age relative to chronological age was associated with increased activation of pro-inflammatory and interferon pathways, and decreased activation of transcriptional/translational machinery, DNA damage response, and mitochondrial signatures.

DNAm PhenoAge is a single epigenetic biomarker of aging that effectively captures risks for diverse outcomes across multiple tissues and cells and provides insights into important aging pathways.


Gut microbiota: A player in aging and a target for anti-aging intervention

Glycan-Based Inflammatory Age Testing;Gut Microbiome Testing;AI Nutrition Tracking;At-Home Food & Allergen Testing

Changes in gut bacteria are linked to aging, and modifying these bacteria through diet, probiotics, or fecal transplants may offer anti-aging benefits.

What role does gut microbiota play in aging, and what is the therapeutic potential of microbiome-targeted interventions for anti-aging?

Hypothesis: The abstract suggests that age-related changes in gut microbiota contribute to aging processes, and that interventions targeting the microbiota could favorably affect host health and aging.

This is a review article summarizing recent research findings on the role of gut microbiota in aging processes and the therapeutic potential of microbiome-targeted interventions.

Aging is associated with alterations in gut microbiota composition, diversity, and function, potentially due to immunosenescence and inflammaging. Microbiota-targeted dietary and probiotic interventions have been shown to enhance antioxidant activity, improve immune homeostasis, suppress chronic inflammation, regulate fat deposition and metabolism, and prevent insulin resistance. Fecal microbiota transplantation has also demonstrated high effectiveness and safety in preventing and treating age-related conditions like atherosclerosis, type 2 diabetes, and Parkinson's disease.

Gut microbiota plays a significant role in aging processes, and microbiome-targeted interventions, including dietary changes, probiotics, and fecal microbiota transplantation, hold therapeutic potential for anti-aging medicine and the management of age-related pathologies.

As a review, this abstract does not present new experimental data or specific study limitations beyond what might be inherent in the reviewed literature. It summarizes existing findings without detailing the limitations of individual studies.


Continuous Glucose Monitoring and Physical Activity

International Journal of Environmental Research and Public Health

Continuous Glucose Monitoring (CGM);At-Home Urine Analysis;AI Nutrition Tracking

Continuous glucose monitoring helps people with diabetes manage blood sugar during physical activity and prevents low blood sugar events.

What are the benefits of continuous glucose monitoring (CGM) for people with diabetes, particularly in relation to physical activity, and what are the guidelines for its use?

Hypothesis: The authors hypothesize that CGM use can enhance the benefits of physical activity for people with type 2 diabetes and help prevent adverse events like hypoglycemia.

This is a narrative review that synthesizes existing information to provide recommendations and an overview of guidelines regarding CGM use and physical activity for people with diabetes.

The review notes that CGM use offers benefits such as increased time in range (TIR), optimized therapy, and improved documentation for diabetes management. For people with type 2 diabetes, physical activity improves glycemic control, glycemic variability, and reduces insulin resistance. The benefits of CGM are further increased when combined with physical activity, as CGM can help prevent adverse events like hypoglycemic events and nocturnal hypoglycemia after exercise.

CGM is a helpful tool for people with diabetes engaging in physical activity, as it can enhance the benefits of exercise and prevent adverse glycemic events.

This is a narrative review, which synthesizes existing literature rather than presenting new experimental data. Specific quantitative data or direct comparisons are not provided.


The impact of visit-to-visit heart rate variability on all-cause mortality

Comprehensive Blood-Biomarker Testing;Biometric Wearables (Sleep, HRV & Recovery);Heart-Rate-Variability & Autonomic Tools;Neurofeedback & Stress-Resilience Devices;Optical Biomarker Scanning;Smart Body-Composition Analysis

Both very low and very high heart rate variability between doctor visits are linked to a higher risk of death in people with atrial fibrillation.

What is the association between visit-to-visit heart rate variability (VVHRV) and all-cause mortality in patients with atrial fibrillation (AF)?

Hypothesis: The relationship between VVHRV and the prognosis of AF is uncertain, but previous studies suggest a correlation between VVHRV and adverse outcomes.

The study examined 3983 participants with AF from the AFFIRM study. VVHRV was measured using the standard deviation of heart rate (HRSD), and patients were divided into four quartiles based on HRSD. Cox proportional hazard regressions were used to estimate hazard ratios for all-cause mortality.

During an average follow-up of 3.5 years, 621 participants died. Both the lowest and highest quartiles of HRSD independently predicted an increased risk of all-cause mortality compared to the second and third quartiles, showing a U-shaped relationship. Specifically, the 1st quartile had hazard ratios of 2.28 (vs 2nd) and 2.23 (vs 3rd), while the 4th quartile had hazard ratios of 1.82 (vs 2nd) and 1.78 (vs 3rd).

In patients with AF, both lower and higher visit-to-visit heart rate variability are associated with an increased risk of all-cause mortality, forming a U-shaped curve.


Association between sauna bathing and fatal cardiovascular and all-cause mortality events

Contrast Therapy Systems (Sauna + Cold + Light);Infrared & Traditional Saunas;Cold Plunge & Ice-Bath Systems

More frequent and longer sauna bathing sessions are associated with a lower risk of cardiovascular and all-cause mortality in middle-aged men.

favorable-cue: "associated with a reduced"

What is the association between the frequency and duration of sauna bathing and the risk of sudden cardiac death (SCD), fatal coronary heart disease (CHD), fatal cardiovascular disease (CVD), and all-cause mortality?

Hypothesis: The study aims to investigate the association of sauna bathing with cardiovascular and all-cause mortality, as this relationship is currently unknown despite sauna bathing being linked to better hemodynamic function.

This was a prospective cohort study (Finnish Kuopio Ischemic Heart Disease Risk Factor Study) involving 2315 middle-aged men (42-60 years) from Eastern Finland. Baseline examinations were conducted from March 1, 1984, through December 31, 1989, and the frequency and duration of sauna bathing were assessed at baseline. Participants were followed for a median of 20.7 years.

During the follow-up, there were 190 SCDs, 281 fatal CHDs, 407 fatal CVDs, and 929 all-cause mortality events. Men who had 4 to 7 sauna sessions per week had a hazard ratio of 0.37 for SCD compared to those with 1 session per week, and similar inverse associations were found for CHD, CVD, and all-cause mortality. For duration, sessions lasting more than 19 minutes had a hazard ratio of 0.48 for SCD compared to sessions less than 11 minutes, with similar findings for fatal CHDs and fatal CVDs, but not for all-cause mortality.

Increased frequency of sauna bathing is associated with a reduced risk of sudden cardiac death, coronary heart disease, cardiovascular disease, and all-cause mortality. Longer duration of sauna bathing is also associated with reduced risks of SCD, fatal CHD, and fatal CVD.

The abstract does not explicitly state limitations of the study. It does suggest that further studies are warranted to establish the potential mechanism linking sauna bathing and cardiovascular health.


The effects of cold water immersion and active recovery on inflammation and cell stress responses in human skeletal muscle after resistance exercise

Contrast Therapy Systems (Sauna + Cold + Light);Cold Plunge & Ice-Bath Systems

Cold water immersion is not superior to active recovery for reducing muscle inflammation and stress after resistance exercise.

Does cold water immersion reduce inflammation and cellular stress in human skeletal muscle after resistance exercise more effectively than active recovery?

Hypothesis: The study implicitly tests the common assumption that cold water immersion reduces inflammation in skeletal muscle.

Nine active men performed unilateral lower-body resistance exercise on two separate days. After exercise, they either immersed their lower body in 10°C cold water for 10 minutes or cycled at a low intensity for 10 minutes (active recovery). Muscle biopsies were collected before, 2, 24, and 48 hours after exercise to assess inflammatory cells, pro-inflammatory cytokines, neurotrophins, and heat shock proteins.

Exercise increased intramuscular neutrophil and macrophage counts, MAC1 and CD163 mRNA expression, and the mRNA expression of several pro-inflammatory cytokines (IL1β, TNF, IL6, CCL2, CCL4, CXCL2, IL8, LIF). Neurotrophin expression (NGF and GDNF mRNA) also increased, and cytosolic αB-crystallin and HSP70 protein content decreased, with corresponding increases in cytoskeletal αB-crystallin and type II fiber staining. However, there were no significant differences in these inflammatory and stress responses between the cold water immersion and active recovery treatments.

Cold water immersion is not more effective than active recovery in minimizing inflammatory and cellular stress responses in human skeletal muscle after resistance exercise.

The study involved a small sample size of nine active men, and the findings may not be generalizable to other populations or exercise types.


Mechanisms and applications of the anti-inflammatory effects of photobiomodulation.

Contrast Therapy Systems (Sauna + Cold + Light);Photobiomodulation (Red & Near-Infrared Light);Red-Light Skin Therapy

Photobiomodulation uses red and near-infrared light to reduce inflammation by influencing cellular processes like energy production, antioxidant defenses, and gene expression.

What are the mechanisms and applications of the anti-inflammatory effects of photobiomodulation (PBM)?

Hypothesis: The abstract does not explicitly state a hypothesis, but rather reviews the known mechanisms and applications of PBM's anti-inflammatory effects.

This is a review article summarizing existing research on the mechanisms and applications of photobiomodulation (PBM). It discusses primary, secondary, and tertiary effects of light absorption, as well as observed outcomes in various cell types and animal models.

PBM's primary chromophores are cytochrome c oxidase and calcium ion channels. Secondary effects include increased ATP, a brief burst of reactive oxygen species (ROS), increased nitric oxide, and modulated calcium levels. Tertiary effects involve activation of transcription factors, leading to improved cell survival, proliferation, migration, and new protein synthesis. PBM exhibits a biphasic dose response, with low light levels stimulating and high levels inhibiting. PBM can produce ROS in normal cells but lowers ROS in oxidatively stressed cells and disease models, up-regulating anti-oxidant defenses. It activates NF-kB in normal cells but decreases inflammatory markers in activated inflammatory cells. PBM reduces inflammation in joints, traumatic injuries, lung disorders, and the brain, and has been shown to reduce M1 phenotype markers in activated macrophages, as well as reactive nitrogen species and prostaglandins in animal models.

Photobiomodulation (PBM) effectively reduces inflammation through multiple mechanisms, including modulation of mitochondrial activity, calcium levels, reactive oxygen species, and transcription factors. Its anti-inflammatory effects are reproducible across various tissues and disease models, making it a promising therapeutic approach for inflammatory disorders.

The abstract does not explicitly state limitations of the research reviewed or PBM itself, as it is a summary of known mechanisms and applications.


Systematic review of light exposure impact on human circadian rhythm.

Sleep Optimization & Circadian Systems;Blue-Light Management & Circadian Lighting

Even low levels of various light types, especially blue and violet light, can rapidly disrupt human circadian rhythms and melatonin production, informing future light pollution assessments.

What is the impact of light exposure on human circadian rhythm, and how can this information be used to develop an evaluation method for light pollution in life cycle assessment (LCA)?

Hypothesis: Mistimed light exposure disrupts the human circadian rhythm, potentially leading to health impacts, and a systematic review is needed to synthesize existing research to inform light pollution evaluation in LCA.

A systematic literature search was conducted using the concepts 'light' and 'circadian rhythm,' with additional terms 'melatonin' and 'rapid-eye-movement (REM) sleep.' The search yielded 128 articles. Data was collected and analyzed from these articles, with a focus on melatonin secretion (122 articles) and REM sleep (13 articles). Studies were categorized by light exposure type (specific vs. prevailing conditions). Quality criteria for further synthesis included a minimum sample size of 20 subjects and detailed light exposure information (spectrum/wavelength, illuminance/irradiance/photon density). This resulted in 13 qualified studies on melatonin and 2 on REM sleep for further analysis.

A two-hour exposure to blue light (460 nm) in the evening suppressed melatonin, with the maximum suppression occurring at the shortest wavelengths (424 nm, violet). Melatonin concentration recovered within 15 minutes after light cessation. Melatonin secretion and suppression decreased with age, but light-induced circadian phase advance was not impaired by age. Light exposure in the evening, at night, and in the morning affected the circadian phase of melatonin levels. Even long wavelengths (631 nm, red) and intermittent light exposures induced circadian resetting, and low light levels (5-10 lux) at night with eyes closed also induced a circadian response.

Light exposure significantly impacts human circadian rhythm, with blue and violet light being particularly effective at suppressing melatonin. The effects are rapid and can occur even with long wavelengths, intermittent exposure, and low light levels during sleep. This review provides a basis for developing an evaluation method for light pollution in life cycle assessment concerning human circadian impacts.

Many studies had small sample sizes (39 out of 128 studies had 10 or fewer subjects). The review focused primarily on adults in their twenties or thirties, with very few studies on children and elderly adults. The variety of methods used in individual experimental studies, including definitions of light exposure and outcomes, posed a challenge for synthesis.


Long-term exposure to ambient air pollution is a risk factor for trajectory of cardiometabolic multimorbidity: A prospective study in the UK Biobank.

Long-term exposure to air pollution increases the risk of developing cardiometabolic diseases, progressing to multimorbidity, and all-cause mortality, especially in certain vulnerable groups.

Does long-term exposure to ambient air pollution affect the onset, progression, and prognosis of cardiometabolic multimorbidity (CMM)?

Hypothesis: The study aims to investigate the association between air pollution and the trajectory of CMM, as this has not been previously studied.

This prospective analysis used data from the UK Biobank cohort, including 410,494 middle- and old-age participants. CMM was defined as the presence of at least two cardiometabolic diseases (type 2 diabetes, ischemic heart disease, or stroke). A multi-state model was used to analyze the association between air pollution and the trajectory of CMM.

During a median follow-up of 12.0 years, 56,877 participants developed a first cardiometabolic disease (FCMD), 8,616 developed CMM, and 22,423 died. Per interquartile range increase of fine particulate matter, the risks of transitioning from baseline to FCMD, FCMD to CMM, and baseline to all-cause mortality increased by 3%, 3%, and 5% respectively. The risk of transitioning from FCMD to all-cause mortality increased by 2%. For nitrogen dioxide, the corresponding increases were 3%, 6%, 4%, and 6%. Older participants, males, and individuals with excessive alcohol drinking and lower economic levels were more susceptible to these risks.

Exposure to air pollution may play a significant role in nearly all transition phases of CMM development. Clean air could serve as an upstream strategy to reduce both the initiation and progression of CMM, particularly in vulnerable populations.

The abstract does not explicitly state any limitations of the study.


Prevalence of exposure of heavy metals and their impact on health consequences.

Water Purification (Reverse Osmosis & Ultrafiltration)

Drinking water contaminated with heavy metals is a widespread problem causing significant health issues globally.

What is the global prevalence of heavy metal contamination in drinking water and its associated health hazards?

Hypothesis: The abstract does not explicitly state a hypothesis, but it implies that heavy metal contamination in drinking water is a significant health concern leading to various adverse health outcomes.

This article is a review that discusses the global contamination of drinking water with heavy metals, assesses associated health hazards, reviews the relationship between exposure limits and responses, and discusses acute and chronic poisoning symptoms and mechanisms.

Heavy metals such as arsenic, cadmium, nickel, mercury, chromium, zinc, and lead are present in drinking water above recommended limits. The predominant source of human exposure is contaminated drinking water, leading to health issues including cardiovascular disorders, neuronal damage, renal injuries, and increased risk of cancer and diabetes. The general mechanism of toxicity involves the production of reactive oxygen species and oxidative damage.

Consumption of heavy metal-contaminated water contributes to high morbidity and mortality rates globally due to the production of reactive oxygen species and subsequent oxidative damage, leading to various adverse health effects.

As a review article, this study synthesizes existing information and does not present new experimental data or specific quantitative findings on prevalence or health impacts.


A controlled trial to determine the efficacy of red and near-infrared light treatment in patient satisfaction, reduction of fine lines, wrinkles, skin roughness, and intradermal collagen density increase.

Photobiomodulation (Red & Near-Infrared Light);Red-Light Skin Therapy

Red and near-infrared polychromatic light treatment can improve skin complexion, feeling, roughness, and collagen density, but a broader spectrum did not offer additional benefits over red light alone.

Does polychromatic red and near-infrared light treatment improve skin feeling, appearance, and intradermal collagen density compared to controls?

Hypothesis: The study hypothesized that polychromatic light, covering a broader spectral region, would be favorable for skin rejuvenation and repair compared to narrower bandwidth light sources.

This was a prospective, randomized, and controlled study with 136 volunteers. 113 subjects were randomly assigned to four treatment groups, receiving either 611-650 nm or 570-850 nm polychromatic light twice a week for 30 sessions, normalized to approximately 9 J/cm² in the 611-650 nm range. These groups were compared to 23 controls. Data collected included blinded evaluations of clinical photography, ultrasonographic collagen density measurements, computerized digital profilometry, and patient satisfaction.

Treated subjects showed significantly improved skin complexion, skin feeling, skin roughness (assessed profilometrically), and ultrasonographically measured collagen density. Blinded clinical evaluation of photographs confirmed significant improvement in the intervention groups compared to the control group. Broadband polychromatic PBM did not show an advantage over the red-light-only spectrum.

Both novel polychromatic light sources demonstrated efficacy and safety for skin rejuvenation and increasing intradermal collagen when compared with controls. However, broadband polychromatic PBM did not offer an advantage over the red-light-only spectrum.

The abstract does not explicitly state limitations of the study.


Sleep duration and risk of all-cause mortality: a systematic review and meta-analysis.

Sleep Optimization & Circadian Systems;Blue-Light Management & Circadian Lighting;Nasal-Breathing Sleep Tape;Biometric Wearables (Sleep, HRV & Recovery);Neurofeedback & Stress-Resilience Devices

Sleeping more than 9 hours per night is associated with an increased risk of all-cause mortality, but this might be due to underlying health issues.

unfavorable-cue: "higher all-cause mortality" | no-difference-cue: "no significant association"

What is the association between sleep duration and the risk of all-cause mortality in adults?

Hypothesis: The study aimed to determine the association between sleep duration and all-cause mortality, with planned comparisons of sleep durations less than 7 hours and greater than 9 hours against a reference of 7-9 hours.

A systematic review and meta-analysis of cohort studies were conducted using MEDLINE, CENTRAL, EMBASE, and LILACS databases, along with other databases and unpublished literature. The risk of bias was assessed using a modified Cochrane Collaboration's tool. A random effects analysis was performed, with all-cause mortality as the primary outcome and risk difference (RD) with 95% confidence intervals as the effect measure. Comparisons were made between <7 hours of sleep versus 7-9 hours, and >9 hours of sleep versus 7-9 hours.

Thirty-nine studies were included in the qualitative analysis. For quantitative analysis, 19 studies compared <7 hours of sleep to 7-9 hours, and 18 studies compared >9 hours to 7-9 hours. Most studies showed a low risk of bias. The overall risk difference for all-cause mortality was 0.09 (95% CI 0.07-0.11) when comparing the >9 hours group to the 7-9 hours reference, favoring the reference group. No significant difference was found between the <7 hours group and the 7-9 hours reference group (RD 0.00, 95% CI 0.00-0.01).

There is a probable association between long sleep duration (>9 hours) and higher all-cause mortality. However, no significant association was found for short sleep duration (<7 hours) compared to the 7-9 hour reference.

The observed association between long sleep duration and higher mortality might reflect underlying systemic or neurological diseases that cause sleep fragmentation, deterioration in quality, and micro-awakenings, rather than long sleep duration itself being a direct cause.


Fisetin is a senotherapeutic that extends health and lifespan.

All-in-One Longevity Formulation;Fisetin Senolytic Capsules

Fisetin, a natural flavonoid, acts as a potent senolytic in mice and human tissues, reducing age-related pathology and extending lifespan when administered late in life.

Can flavonoids be identified that have more potent senolytic activity than previously known combinations, and can these extend health and lifespan?

Hypothesis: The researchers hypothesized that certain flavonoid polyphenols would exhibit potent senolytic activity, potentially surpassing existing treatments, and that this activity could translate into improved health and extended lifespan in animal models.

A panel of 10 flavonoid polyphenols was screened for senolytic activity using senescent murine and human fibroblasts. The most potent flavonoid, fisetin, was then tested in mice modeling a progeroid syndrome and in aged wild-type mice to assess its effects on senescence markers, age-related histopathology, disease markers, health span, and lifespan. Human adipose tissue explants were also used to evaluate the translatability of the results.

Fisetin was identified as the most potent senolytic among the 10 flavonoids tested. Acute or intermittent treatment with fisetin reduced senescence markers in multiple tissues in progeroid and old mice, indicating a 'hit-and-run' senolytic mechanism. Fisetin also reduced senescence in specific cell types within murine and human adipose tissue. In wild-type mice, late-life administration of fisetin restored tissue homeostasis, reduced age-related pathology, and extended both median and maximum lifespan.

The natural product fisetin possesses senotherapeutic activity in mice and human tissues. Intervention with fisetin late in life was sufficient to provide significant health benefits, suggesting its potential for translation into human clinical studies.

The study primarily used mouse models and human tissue explants, which may not fully reflect the complexity of human aging and disease. The specific mechanisms of fisetin's cell-type specificity were not fully elucidated.


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

Urolithin A (Mitopure);Pomegranate Ellagitannin Extract

Urolithin A supplementation improved muscle strength and exercise performance in middle-aged adults, along with markers of mitochondrial health.

Can Urolithin A improve muscle strength, exercise performance, and biomarkers of mitochondrial health in middle-aged adults?

Hypothesis: Targeting mitophagy to activate the recycling of faulty mitochondria during aging with Urolithin A will mitigate muscle decline.

This was a randomized, placebo-controlled trial where middle-aged adults received either Urolithin A (Mitopure) at two different doses or a placebo for 4 months. The study assessed muscle strength, aerobic endurance (peak oxygen consumption), physical performance (6-minute walk test), peak power output, plasma acylcarnitines, C-reactive proteins, and expression of proteins linked to mitophagy and mitochondrial metabolism in skeletal muscle.

Urolithin A intake led to significant improvements in muscle strength (approximately 12%). Clinically meaningful improvements were observed in aerobic endurance (peak oxygen consumption) and physical performance (6-minute walk test). However, there was no significant improvement in peak power output. Plasma acylcarnitines and C-reactive proteins were significantly lower with Urolithin A, and there was a significant increase in the expression of proteins linked to mitophagy and mitochondrial metabolism in skeletal muscle.

Urolithin A improves muscle performance, muscle strength, aerobic endurance, and physical performance, and positively impacts biomarkers of mitochondrial health and inflammation in middle-aged adults.


Evidence: sulforaphane reduces hepatic gluconeogenesis

Broccoli sprout extract did not significantly lower fasting blood glucose in all prediabetic individuals, but a subgroup with specific characteristics showed a more positive response linked to gut microbiota.

no-difference-cue: "did not meet" | favorable-cue: "reduction in fasting blood glucose"

Can sulforaphane, delivered as a broccoli sprout extract (BSE), reduce hepatic gluconeogenesis and improve fasting blood glucose in individuals with prediabetes?

Hypothesis: Sulforaphane, provided as a broccoli sprout extract, will reduce fasting blood glucose in individuals with prediabetes.

A randomized, double-blind, placebo-controlled trial was conducted with drug-naive individuals with prediabetes. Participants received either BSE (n=35) or placebo (n=39) once daily for 12 weeks. The primary outcome was a 0.3 mmol/l reduction in fasting blood glucose compared to placebo from baseline to week 12. Gastrointestinal side effects were monitored.

BSE did not meet the prespecified primary outcome of a 0.3 mmol/l reduction. The overall effect in individuals with prediabetes was a 0.2 mmol/l reduction in fasting blood glucose. Exploratory analyses identified a subgroup of individuals with mild obesity, low insulin resistance, and reduced insulin secretion who had a 0.4 mmol/l reduction. Gut microbiota analysis showed responders had a different gut microbiota composition, with a higher abundance of a Bacteroides-encoded transcriptional regulator linked to sulforaphane activation and serum concentration.

While BSE did not meet its primary endpoint for the overall prediabetes population, a subgroup of individuals with specific pathophysiological and gut microbiota characteristics showed a more pronounced reduction in fasting blood glucose. This suggests a combined influence of host pathophysiology and gut microbiota on the metabolic response to sulforaphane.

The primary outcome was not met for the overall study population. The findings regarding subgroups and gut microbiota are based on exploratory analyses and require confirmation in future trials.


Evidence: lowers CRP, IL-6, TNF-alpha

Curcumin supplementation can reduce several markers of inflammation in humans, but more research is needed to determine optimal usage.

Does curcumin supplementation effectively reduce systemic inflammatory mediators in humans?

Hypothesis: The study implicitly hypothesizes that curcumin, a known anti-inflammatory agent in preclinical research, will demonstrate efficacy in reducing systemic inflammatory mediators in humans.

This systematic review and meta-analysis searched Medline, CINAHL, EMBASE, Scopus, and Cochrane databases for randomized controlled trials from 1980 to May 2019. Eligible studies investigated dietary curcumin's effects on inflammatory mediators in humans not receiving anti-inflammatory treatment. Two authors independently screened articles, and evidence quality was appraised using the Quality Criteria Checklist for Primary Research. Thirty-two trials were included, and 28 were meta-analyzed using a random-effects model.

Pooled data from 28 meta-analyzed trials (N = 2,038 participants) showed that curcumin supplementation significantly reduced C-reactive protein (-1.55 mg/L), interleukin-6 (-1.69 pg/mL), tumor necrosis factor " (-3.13 pg/mL), IL-8 (-0.54 pg/mL), and monocyte chemoattractant protein-1 (-2.48 pg/mL). It also increased IL-10 (0.49 pg/mL), but had no effect on intracellular adhesion molecule-1.

Curcumin supplementation demonstrates anti-inflammatory effects by reducing several systemic inflammatory mediators and increasing IL-10. Further research is needed to optimize dose, duration, and formulation for chronic inflammation in humans.

The abstract does not explicitly state limitations of the review, but it does highlight that clinical evidence for curcumin remains inconclusive due to discrepancies regarding optimal dosage, duration, and formulation, suggesting these are areas needing further clarification.


Evidence: lowers systolic/diastolic blood pressure

Quercetin supplementation can lower both systolic and diastolic blood pressure depending on the individual's blood pressure status.

favorable-cue: "decreases blood pressure"

Does quercetin supplementation affect systolic and diastolic blood pressure?

Hypothesis: The meta-analysis aimed to summarize data on quercetin's impact on systolic blood pressure (SBP) and diastolic blood pressure (DBP) to clarify its effects.

A meta-analysis was conducted by searching Medline, EMBASE, and Web of Science databases for randomized controlled trials assessing quercetin's impact on blood pressure until May 2022. A random-effects model was used for data analysis, and subgroup analysis explored effects in (pre)hypertensive and normotensive adults. Ten trials with 841 participants were included.

Quercetin supplementation significantly decreased SBP in the mixed population by 2.38 mmHg and in the normotensive subgroup by 1.82 mmHg. It also significantly decreased DBP in the (pre)hypertensive subgroup by 3.14 mmHg.

Quercetin supplementation decreases blood pressure in both normotensive and (pre)hypertensive patients.

The abstract does not explicitly state any limitations of the meta-analysis.


Evidence: activates AMPK, reduces lipid absorption

Tea's health benefits may stem from reducing nutrient absorption and activating a key metabolic enzyme, AMPK.

What are the fundamental mechanisms by which tea consumption reduces body weight, alleviates metabolic syndrome, and prevents diabetes and cardiovascular diseases?

Hypothesis: The two major mechanisms for tea's beneficial effects are decreasing absorption of lipids and proteins in the intestine and activating AMP-activated protein kinase (AMPK) by tea polyphenols in the liver, skeletal muscle, and adipose tissues.

This study is a review of existing literature, proposing mechanisms based on previously published research.

The proposed mechanisms are: (i) reduced absorption of lipids and proteins in the intestine by tea constituents, leading to decreased calorie intake; and (ii) activation of AMP-activated protein kinase by bioavailable tea polyphenols in the liver, skeletal muscle, and adipose tissues. Activated AMPK would decrease gluconeogenesis and fatty acid synthesis while increasing catabolism.

Tea's beneficial effects on body weight and metabolic syndrome are likely mediated by reduced lipid and protein absorption and activation of AMPK. The relative importance of these mechanisms may vary with tea type and diet.

The study acknowledges that other mechanisms and the full health relevance of tea consumption's beneficial effects require further investigation.


Evidence: raises antioxidant capacity, lowers MDA

Astaxanthin supplementation improved markers of inflammation and oxidative stress, and enhanced ART outcomes in infertile women with endometriosis.

What is the effect of Astaxanthin (AST) on pro-inflammatory cytokines, oxidative stress (OS) markers, and early pregnancy outcomes in infertile women with endometriosis undergoing assisted reproductive techniques (ART)?

Hypothesis: The study hypothesized that Astaxanthin (AST) treatment would modulate inflammation and oxidative stress markers, and improve early pregnancy outcomes in infertile women with endometriosis undergoing ART.

This was a randomized, triple-blind, placebo-controlled clinical trial involving 50 infertile women with stage III/IV endometriosis who were candidates for ART. Participants received 6 mg of AST per day for 12 weeks. Blood serum and follicular fluid (FF) samples were collected before and after treatment to measure pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and OS markers (MDA, SOD, CAT, TAC). ART outcomes were also compared between the groups.

After AST therapy, the treatment group showed increased serum levels of TAC (398.661 vs. 364.746) and SOD (13.458 vs. 9.040), and decreased serum MDA (14.619 vs. 15.939). Significantly lower serum levels of IL-1β (4.515 vs. 6.8760), IL-6 (5.516 vs. 5.0543), and TNF-α (2.520 vs. 2.968) were also observed. Additionally, AST supplementation led to an improved number of oocytes retrieved (14.60 vs. 9.84), mature (MII) oocytes (10.48 vs. 6.72), and high-quality embryos (4.52 vs. 2.72).

AST pretreatment can modulate inflammation and oxidative stress in infertile patients with endometriosis, and improve ART outcomes after 12 weeks of therapy. These results suggest AST could be a potential therapeutic target for this patient population.


Evidence: plasma ergothioneine, cytoprotection

Higher levels of the metabolite ergothioneine are linked to a lower risk of heart disease, diabetes, and death.

What are the molecular events linking a healthy food pattern to reduced risk of cardiometabolic disease?

Hypothesis: Plasma metabolites associated with a health conscious food pattern (HCFP) will predict cardiometabolic disease and mortality.

Plasma levels of 112 metabolites were measured in 3236 participants from the Malmö Diet and Cancer study using liquid-chromatography mass-spectrometry. Participants had no history of cardiovascular disease or diabetes. Multivariable adjusted linear regressions identified metabolites associated with the HCFP. These biomarkers were then related to the risk of cardiometabolic disease and mortality using multivariable adjusted Cox proportional hazards models during long-term follow-up.

During a median follow-up of 21.4 years, 603 participants developed CVD, 362 developed diabetes mellitus, and 843 died. Five healthy dietary biomarkers were associated with the HCFP at baseline, and four of these predicted at least one of the studied endpoints. Ergothioneine was the metabolite most strongly connected to the HCFP and was associated with a lower risk of coronary disease (HR=0.85), cardiovascular mortality (HR=0.79), and overall mortality (HR=0.86) per 1 SD increment.

Higher plasma ergothioneine is an independent marker of lower risk of cardiometabolic disease and mortality, potentially influenced by a healthy dietary intake.

The study identified associations but did not establish causality between ergothioneine levels and reduced risk. The specific dietary components of the HCFP that induce higher ergothioneine were not detailed.


Evidence: oleuropein lowers BP and LDL

Olive leaf extract may help lower blood pressure and cholesterol in pre-hypertensive men.

What are the effects of a phenolic-rich olive leaf extract (OLE) on blood pressure and associated vascular and metabolic measures in pre-hypertensive males?

Hypothesis: The study hypothesized that a phenolic-rich olive leaf extract would favorably modify cardiovascular risk markers such as blood pressure, endothelial function, and plasma lipids.

This was a randomized, double-blind, controlled, crossover trial involving 60 pre-hypertensive males. Participants consumed either OLE (136 mg oleuropein; 6 mg hydroxytyrosol) or a polyphenol-free control daily for 6 weeks, followed by a 4-week washout period before switching to the alternate arm.

Compared to the control, OLE intake significantly lowered daytime SBP by 3.95 mmHg, 24-h SBP by 3.33 mmHg, daytime DBP by 3.00 mmHg, and 24-h DBP by 2.42 mmHg. OLE also reduced plasma total cholesterol by 0.32 mmol/L, LDL cholesterol by 0.19 mmol/L, triglycerides by 0.18 mmol/L, and interleukin-8 by 0.63 pg/ml. Other markers of inflammation, vascular function, and glucose metabolism were not affected.

The study concluded that olive leaf extract intake has hypotensive and lipid-lowering effects in pre-hypertensive males, supporting previous research.


Evidence: precursor to urolithins, mitophagy

Urolithins, derived from certain foods, show potential as therapeutic agents for various diseases and antiaging, partly by improving mitochondrial function.

What are the potential therapeutic roles and molecular mechanisms of urolithins, particularly urolithin A, in various diseases and antiaging?

Hypothesis: Urolithins, gut metabolites from ellagitannin-rich foods, possess various biological activities including cardiovascular protection, anti-inflammatory, anticancer, antidiabetic, and antiaging properties, mediated by several cellular mechanisms.

This is a comprehensive review of existing in vitro, in vivo, and clinical studies on urolithins, focusing on their biological effects, molecular pathways, and pharmacokinetics.

Urolithins exhibit beneficial effects in diseases like Alzheimer's, type 2 diabetes, liver disease, cardiovascular disease, and various cancers. Their mechanisms include inhibiting MDM2-p53 interaction, modulating the MAPK pathway, and suppressing NF-κB activity. Urolithin A's antiaging activity is linked to activating mitophagy and mitochondrial biogenesis. A clinical trial showed urolithin A is safe up to 2,500 mg/day and improves mitochondrial biomarkers in elderly patients.

Urolithins, particularly urolithin A, show promise as therapeutic agents due to their diverse biological activities and involvement in key cellular mechanisms, including mitophagy and mitochondrial biogenesis. Further clinical research is warranted.

The abstract does not explicitly state limitations of the reviewed studies or the review itself, but it emphasizes the need for further clinical trials.


Evidence: improves endothelial function, lowers BP

A specific grape seed extract improved markers of endothelial function in cells and lowered blood pressure in healthy human volunteers, also showing a positive effect on perceived stress.

What are the effects of a specific grape seed extract (GSEe) on vascular inflammation, vasodilation, and blood pressure in both in vitro and human models?

Hypothesis: The study hypothesized that GSEe, a standardized grape seed extract, would positively modulate endothelial function and blood pressure.

The study used an in vitro human umbilical vein endothelial cell (HUVEC) model to assess GSEe's effects on vascular inflammation and vasodilation markers. A randomized, double-blind, placebo-controlled clinical study was also conducted in healthy volunteers, with participants receiving 300 mg/day of GSEe tablets for 16 weeks, to investigate its benefits on blood pressure and mood.

In HUVEC cells, GSEe significantly reduced the secretion/release of soluble Inter-Cellular Adhesion Molecule-1 (sICAM) and endothelin-1. In healthy human volunteers, GSEe supplementation significantly modulated blood pressure, showing a more pronounced effect compared to placebo. This blood pressure modulation was observed in the male subgroup, where no placebo effect was noted, unlike in the female group. Additionally, GSEe showed a positive modulation on mood related to stress perception.

GSEe beneficially modulates endothelial functionality and blood pressure. It also relieved perceived stress, suggesting potential for mood comfort.


Evidence: improves liver enzymes, lipids

Silymarin supplementation may improve liver enzymes, lipid profiles, and liver histology in individuals with nonalcoholic fatty liver disease.

Does silymarin improve outcomes in patients with nonalcoholic fatty liver disease (NAFLD)?

Hypothesis: The study implicitly hypothesizes that silymarin, a hepatoprotective extract, may be effective in slowing NAFLD progression.

This meta-analysis included 26 randomized controlled trials with 2,375 patients. Data were extracted from PubMed, Embase, Cochrane Library, Web of Science, clinicaltrials.gov, and China National Knowledge Infrastructure. Continuous values were pooled using standard mean difference (SMD) and dichotomous values using odds ratio (OR). Heterogeneity was assessed with Cochran's Q test (Istatistic), and statistical significance was set at P<0.05.

Silymarin significantly reduced total cholesterol (TC), triglycerides (TG), LDL-C, FI, HOMA-IR, ALT, AST, fatty liver index, and fatty liver score. It also increased HDL-C and significantly improved hepatic steatosis based on liver histology. Specifically, ALT decreased by an SMD of -12.39, AST by -10.97, and hepatic steatosis showed an OR of 3.25 for improvement.

Silymarin can regulate energy metabolism, attenuate liver damage, and improve liver histology in patients with NAFLD.

The abstract states that the effects of silymarin will need to be confirmed by further research.


Evidence: lowers adhesion molecules, BP

Hesperidin 2S may offer cardiovascular benefits by reducing adhesion molecules and blood pressure, particularly in overweight individuals with a relatively healthy endothelium.

no-difference-cue: "did not improve" | favorable-cue: "benefits"

Does hesperidin 2S supplementation improve endothelial function in overweight individuals?

Hypothesis: Hesperidin, a citrus flavonoid, may exert beneficial effects on endothelial function due to its antioxidant and other biological properties.

This was a randomized, double-blind, placebo-controlled study where 68 overweight individuals received either 450 mg/d of hesperidin 2S or a placebo for 6 weeks. Researchers assessed flow-mediated dilation (FMD), soluble adhesion molecules (sVCAM-1, sICAM-1, sP-selectin), systolic blood pressure (SBP), and diastolic blood pressure (DBP) at baseline and after 6 weeks. Acute endothelial dysfunction was induced by a high-fat meal, with FMD and adhesion molecules measured postprandially. An exploratory analysis was also conducted in subjects with baseline FMD "3%.

No significant change in fasting or postprandial FMD was observed in the total study population after 6 weeks of hesperidin intake. However, there was a trend for a reduction in sVCAM-1, sICAM-1, sP-selectin, SBP, and DBP after 6 weeks of hesperidin treatment. In the exploratory analysis of subjects with baseline FMD ≥3%, hesperidin protected individuals from postprandial endothelial dysfunction (P = 0.050) and significantly downregulated sVCAM-1 and sICAM-1 (all P ≥0.030).

Six weeks of hesperidin 2S consumption did not improve basal or postprandial FMD in the overall study population, but showed a tendency to reduce adhesion molecules and blood pressure. In overweight and obese individuals with a relatively healthy endothelium (baseline FMD ≥3%), hesperidin 2S improved endothelial dysfunction after a high-fat meal and reduced adhesion molecules, suggesting cardiovascular health benefits.

The results reported were not adjusted for multiplicity. The significant findings regarding FMD and adhesion molecules were from an exploratory analysis in a subgroup of participants.


Evidence: inhibits CD38, raises NAD/Sirt3

Inhibition of CD38 with apigenin can reduce diabetic kidney disease by improving the NAD/NADH ratio and Sirt3 activity.

What role does CD38 play in the pathogenesis of diabetic kidney disease (DKD) and can its inhibition mitigate renal injuries?

Hypothesis: The researchers hypothesized that CD38 contributes to DKD pathogenesis by decreasing the NAD/NADH ratio and Sirt3 activity, and that inhibiting CD38 with apigenin would reduce renal injuries.

The study used Zucker diabetic fatty rats to investigate the effects of the CD38 inhibitor apigenin on renal injuries, CD38 expression, NAD/NADH ratio, and Sirt3 activity. Additionally, renal proximal tubular HK-2 cells cultured under high-glucose conditions were used to examine the impact of CD38 inhibition or knockdown on NAD/NADH ratio and Sirt3 activity.

Apigenin significantly reduced renal injuries, including tubulointerstitial fibrosis, tubular cell damage, and pro-inflammatory gene expression in diabetic rats. Apigenin also down-regulated CD38 expression and increased the intracellular NAD/NADH ratio and Sirt3-mediated mitochondrial antioxidative enzyme activity in the kidneys of diabetic rats. In HK-2 cells, both apigenin and CD38 knockdown increased the NAD/NADH ratio and Sirt3 activity under high-glucose conditions.

CD38 plays a crucial role in the pathogenesis of DKD by inhibiting Sirt3 activity and increasing mitochondrial oxidative stress in renal tubular cells. Inhibition of CD38 with apigenin can mitigate these effects and reduce renal injuries.


Evidence: inhibits neuroinflammation, ER stress

Luteolin improved memory and reduced brain inflammation and cellular stress in a mouse model of Alzheimer's disease.

Can luteolin improve memory deficits and reduce neuroinflammation in a triple-transgenic mouse model of Alzheimer's disease?

Hypothesis: Luteolin, a flavonoid with known anti-inflammatory and neuroprotective properties, will have beneficial effects on memory deficits and neuroinflammation in 3xTg-AD mice.

Triple-transgenic Alzheimer's disease (3xTg-AD) mice were treated with luteolin at doses of 20 or 40 mg/kg/day via intraperitoneal injection for 3 weeks. The study also used rat C6 glioma cells treated with luteolin (1 or 10 µM) to investigate its effects on LPS-induced cell proliferation, inflammatory cytokine release, and ER stress.

Luteolin treatment dose-dependently improved spatial learning and memory deficits in 3xTg-AD mice. This was accompanied by inhibition of astrocyte overactivation (GFAP), reduced neuroinflammation (TNF-α, IL-1β, IL-6, NO, COX-2, iNOS protein), and decreased expression of ER stress markers (GRP78, IRE1α) in brain tissues. In rat C6 glioma cells, luteolin dose-dependently inhibited LPS-induced cell proliferation, excessive inflammatory cytokine release, and an increase in the ER stress marker GRP78.

Luteolin is an effective agent for treating learning and memory deficits in 3xTg-AD mice, likely due to its inhibition of ER stress in astrocytes and subsequent reduction of neuroinflammation.

The study was conducted in a mouse model and rat glioma cells, which may not fully translate to human Alzheimer's disease. The specific mechanisms linking ER stress inhibition in astrocytes to improved memory were not fully elucidated.


Evidence: vascular flavanols, cognition

Daily multivitamin-mineral supplementation, but not cocoa extract, improved global cognition, memory, and executive function in older adults over three years.

Does daily administration of cocoa extract (500 mg/day flavanols) or a commercial multivitamin-mineral (MVM) improve cognition in older women and men?

Hypothesis: The study implicitly hypothesized that either cocoa extract or a multivitamin-mineral supplement would improve cognition in older adults.

COSMOS-Mind was a 3-year randomized two-by-two factorial trial involving 2262 participants (mean age 73 years; 60% women; 89% non-Hispanic White). Cognition was assessed annually by telephone using a global cognition composite score derived from multiple tests. The primary outcome was the change in this composite with 3 years of cocoa extract use, and a pre-specified secondary outcome was the change with 3 years of MVM supplementation. Treatment effects were also examined for executive function and memory, and in pre-specified subgroups.

Cocoa extract had no effect on global cognition (mean z-score = 0.03, 95% CI: -0.02 to 0.08; P = .28). Daily MVM supplementation resulted in a statistically significant benefit on global cognition (mean z = 0.07, 95% CI 0.02 to 0.12; P = .007). This MVM effect was more pronounced in participants with a history of cardiovascular disease (no history: 0.06, 95% CI 0.01 to 0.11; history: 0.14, 95% CI -0.02 to 0.31; interaction, nominal P = .01). MVM benefits were also observed for memory and executive function. The interaction between cocoa extract and MVM was not significant.

Cocoa extract did not benefit cognition in older adults. However, daily multivitamin-mineral supplementation for 3 years improved global cognition, episodic memory, and executive function in older adults, with a potentially greater benefit for those with cardiovascular disease.

Additional work is needed to confirm these findings in a more diverse cohort and to identify mechanisms for the MVM effects. The study population was predominantly non-Hispanic White.


Evidence: augments NO, vasodilation

Pycnogenol increases blood vessel dilation by boosting nitric oxide production in healthy young men.

What are the effects of Pycnogenol on endothelium-dependent vasodilation in humans?

Hypothesis: Pycnogenol, an antioxidant-rich extract, may enhance endothelial nitric oxide synthase expression and subsequent nitric oxide release, thereby augmenting endothelium-dependent vasodilation.

This double-blind, randomized, placebo and active drug study evaluated forearm blood flow (FBF) responses to acetylcholine (ACh) and sodium nitroprusside (SNP) in healthy young men. Participants received either 180 mg/day of Pycnogenol (n=8) or placebo (n=8) orally for 2 weeks. FBF was measured using strain-gauge plethysmography before and after treatment. The effect of an NO synthase inhibitor, N(G)-monomethyl-L-arginine, on Pycnogenol-induced FBF response was also assessed.

Neither placebo nor Pycnogenol altered forearm or systemic hemodynamics. Pycnogenol augmented the FBF response to ACh from 13.1 +/- 7.0 to 18.5 +/- 4.0 mL/min per 100 mL tissue (p<0.05), while placebo did not. SNP-stimulated vasodilation was similar before and after treatment in both groups. The NO synthase inhibitor N(G)-monomethyl-L-arginine completely abolished the Pycnogenol-induced augmentation of the FBF response to ACh.

Pycnogenol augments endothelium-dependent vasodilation by increasing nitric oxide production. This suggests Pycnogenol could be useful for treating diseases involving endothelial dysfunction.

The study was conducted on a small sample of healthy young men, which may limit the generalizability of the findings to other populations or conditions.


Evidence: promotes sleep quantity

Certain nutritional interventions like tart cherry juice, herbal supplements, kiwifruit, and protein can improve sleep in athletes and healthy adults, but more specific research is needed for athletic populations.

What nutritional interventions, foods, beverages, and supplements can improve sleep quality and quantity in athletes?

Hypothesis: Nutrition, including specific foods, beverages, and supplements, can improve sleep quality and quantity in athletes.

This narrative review used a semi-systematic approach to search six databases (PubMed, Scopus, CINAHL, EMBASE, SPORTDiscus, and Google Scholar) from inception to November 2020. The search focused on articles relevant to athletes and sporting environments. Due to limited athlete-specific research, inclusion criteria were expanded to include studies on nutritional interventions for sleep in otherwise healthy adults.

High glycemic index carbohydrates showed small benefits for sleep. Tart cherry juice promoted sleep quantity. Herbal supplements enhanced sleep quality. Kiwifruit and protein interventions improved both sleep quality and quantity.

Nutritional interventions are effective for improving sleep quality and quantity. However, more research is needed to determine optimal dose, source, and timing for athletes.

The review noted a paucity of sleep nutrition research specifically in the athlete population, necessitating the inclusion of studies on healthy adults. Further research is required to establish appropriate dosing, sources, and timing for athletes.


Evidence: improves sleep latency, duration

Saffron extract improved objective and subjective measures of sleep quality and duration in people with mild to moderate sleep disorders and anxiety.

Does saffron extract improve sleep quality in individuals with mild to moderate sleep disorders associated with anxiety?

Hypothesis: The study implicitly hypothesized that saffron extract would improve sleep quality, sleep latency, and sleep duration in subjects with mild to moderate sleep disorders associated with anxiety.

A randomized, double-blind, controlled study was conducted with 66 subjects experiencing mild to moderate sleep disorder associated with anxiety. Participants were randomized to receive either a placebo (maltodextrin) or 15.5 mg of saffron extract per day for 6 weeks. Objective sleep data was collected using actigraphy at baseline, mid-intervention, and end of intervention. Subjective sleep quality was assessed using the LSEQ and PSQI questionnaires, and quality of life was assessed with the SF-36 questionnaire.

After 6 weeks, saffron supplementation increased time in bed (actigraphy), improved ease of getting to sleep (LSEQ), and improved sleep quality, sleep latency, sleep duration, and global scores (PSQI). The placebo group showed no changes in these parameters.

Saffron extract may be a natural and safe nutritional strategy to improve sleep duration and quality.

The abstract does not explicitly state any limitations of the study.


Evidence: macular pigment, antioxidant

Carotenoids offer multiple health benefits, particularly for eye health, but more research is needed to confirm their efficacy across all areas.

What are the various health benefits of carotenoids, and what is the current state of evidence regarding their efficacy?

Hypothesis: The abstract does not state a specific hypothesis for a single study, but rather discusses existing evidence and the need for further research on carotenoids.

This abstract is a review of existing evidence and does not describe specific methods for a primary research study.

Carotenoids primarily act as antioxidants. Lutein and zeaxanthin form macular pigment in the eye, and lutein shows strengthening evidence for reducing the progression of age-related macular eye disease and cataracts. Carotenoids also show evidence for improving cognitive function and cardiovascular health, and may help prevent some cancers. However, large population-based supplementation studies have yielded mixed results for some carotenoids.

Carotenoids offer various health benefits, including antioxidant effects, eye health improvements (especially lutein for macular degeneration and cataracts), cognitive function, cardiovascular health, and potential cancer prevention. More research, including clinical studies, is needed to establish and confirm the specific health benefits of different carotenoids.

Large population-based supplementation studies have produced mixed results for some carotenoids, indicating a need for more research to confirm their health benefits.


Evidence: electron-transport cofactor

Ubiquinol supplementation may improve endothelial function in patients with heart failure with reduced ejection fraction.

Does ubiquinol improve peripheral endothelial function in patients with heart failure with reduced ejection fraction (HFrEF)?

Hypothesis: Ubiquinol improves peripheral endothelial function in patients with HFrEF.

This was a randomized, double-blind, placebo-controlled, crossover pilot study involving 14 patients with stable HFrEF. Patients received either ubiquinol 400 mg/day or placebo for 3 months, followed by a 1-month washout period and then crossover to the alternative treatment. Peripheral endothelial function was assessed using the reactive hyperemia index (RHI) and analyzed using the natural logarithm of RHI (LnRHI) before and after each treatment.

Peripheral endothelial function, as assessed by LnRHI, tended to improve with ubiquinol 400 mg/day for 3 months (p = 0.076). Original RHI values significantly improved with ubiquinol treatment (pre-RHI 1.57, post-RHI 1.74, p = 0.026), but not with placebo (pre-RHI 1.67, post-RHI 1.51, p = 0.198).

Ubiquinol 400 mg/day for 3 months significantly improved peripheral endothelial function in patients with HFrEF.

This was a pilot study with a small sample size (14 patients).


Evidence: promotes mitochondrial biogenesis

PQQ shows promise in preventing and treating pulmonary hypertension by improving mitochondrial function and reducing cellular proliferation and inflammation.

What are the effects of pyrroloquinoline quinone (PQQ) on cellular proliferation, apoptosis resistance, mitochondrial and metabolic alterations associated with pulmonary hypertension (PH)?

Hypothesis: The study hypothesizes that PQQ, known to promote mitochondrial biogenesis, may have beneficial effects on the cellular and mitochondrial dysregulations contributing to pulmonary hypertension.

Human pulmonary artery smooth muscle cells (HPASMCs), endothelial cells (PAECs), and primary cultured cardiomyocytes were exposed to hypoxia to induce a PH-like phenotype. Sprague Dawley rats were injected with monocrotaline (MCT) (60 mg/kg, SC, once) to induce pulmonary hypertension. PQQ treatment (2 mg/kg, PO, for 35 days) was administered to the MCT-treated rats.

PQQ treatment attenuated cellular proliferation and promoted apoptosis via a mitochondrial-dependent pathway. In HPASMCs, PQQ prevented mitochondrial and metabolic dysfunctions, improved mitochondrial bioenergetics, preserved respiratory complexes, and reduced insulin resistance. In MCT-treated rats, PQQ treatment (both preventive and curative) significantly attenuated the increase in right ventricle pressure and hypertrophy, reduced endothelial dysfunction and pulmonary artery remodeling, prevented cardiac fibrosis, improved cardiac functions, and reduced inflammation.

PQQ can attenuate mitochondrial and metabolic abnormalities in PASMCs and prevent the development of PH in MCT-treated rats, suggesting its potential as a therapeutic agent for PH.


Evidence: ATP/phosphocreatine energy buffer

Creatine supplementation combined with resistance training may help improve muscle and bone health in older adults and could be a treatment for frailty and cachexia.

What are the effects of creatine supplementation on indices of aging muscle and bone, and can it be justified for treating frailty and cachexia in older adults?

Hypothesis: Creatine monohydrate supplementation, especially with resistance training, may have favorable effects on aging muscle and bone, potentially making it a viable intervention for frailty and cachexia.

This is a narrative review that updates existing research on creatine supplementation's effects on aging muscle and bone, including bone turnover markers. It also presents a rationale for its use in treating frailty and cachexia in older adults.

The review indicates that creatine monohydrate supplementation, particularly when combined with resistance training, shows favorable effects on markers of aging muscle and bone. These musculoskeletal benefits suggest a potential role for creatine in addressing frailty and cachexia.

Creatine supplementation, especially with resistance training, appears to have beneficial effects on aging muscle and bone, providing a possible justification for its use in treating frailty and cachexia in older adults.

This is a narrative review, which synthesizes existing literature but does not present new experimental data. The specific details of the 'evidence' are not quantified within this abstract.


Evidence: conditionally essential amino acid

Taurine levels decline with age, and supplementing taurine improved health and longevity in animals, suggesting it may play a role in human aging.

Does taurine deficiency contribute to aging, and can taurine supplementation improve health span and life span?

Hypothesis: Taurine deficiency is a driver of aging, and its reversal through supplementation can increase health span and life span.

The study observed circulating taurine levels in aging mice, monkeys, and humans. It then investigated the effects of taurine supplementation on health span and life span in mice and monkeys. Mechanistic studies examined taurine's impact on cellular senescence, telomerase deficiency, mitochondrial dysfunction, DNA damage, and inflammaging. Human data correlated taurine concentrations with age-related diseases and measured taurine levels after acute endurance exercise.

Circulating taurine concentrations declined with aging in mice, monkeys, and humans. Taurine supplementation increased health span and life span in mice, and health span in monkeys. Mechanistically, taurine reduced cellular senescence, protected against telomerase deficiency, suppressed mitochondrial dysfunction, decreased DNA damage, and attenuated inflammaging. In humans, lower taurine concentrations correlated with several age-related diseases, and taurine concentrations increased after acute endurance exercise.

Taurine deficiency may be a driver of aging, as its reversal through supplementation increased health span in worms, rodents, and primates, and life span in worms and rodents. Clinical trials are warranted to investigate this in humans.

The study notes that human data showed correlations and an increase after exercise, but direct intervention trials in humans to assess taurine's impact on aging were not conducted. The findings in worms, rodents, and primates need to be confirmed in human clinical trials.


Evidence: collagen and methylation substrate

All-in-One Longevity Formulation;Glycine Powder

Glycine supplementation can reduce daytime sleepiness and fatigue and improve vigilance after acute sleep restriction, possibly by modulating SCN function.

no-difference-cue: "did not alter" | favorable-cue: "improves"

Does glycine improve daytime sleepiness, fatigue, and performance in sleep-restricted healthy subjects, and does it affect circadian rhythms?

Hypothesis: Glycine may improve sleep quality and reduce daytime sleepiness and fatigue, potentially by modulating circadian rhythms.

Healthy subjects with sleep restricted to 25% less than usual for three nights ingested 3g of glycine or placebo before bedtime. Daytime sleepiness and fatigue were assessed using a visual analog scale (VAS) and a questionnaire. Performance was evaluated using a PC performance test program. Additionally, plasma melatonin and the expression of circadian-modulated genes in the rat suprachiasmatic nucleus (SCN) were measured to assess effects on circadian rhythms.

In subjects given glycine, VAS data showed a significant reduction in fatigue and a tendency toward reduced sleepiness. The questionnaire also indicated improved daytime sleepiness and fatigue. PC performance tests revealed significant improvement in psychomotor vigilance. Glycine did not significantly affect plasma melatonin concentrations or the expression levels of clock genes like Bmal1 and Per2. However, a glycine-induced increase in neuropeptides arginine vasopressin and vasoactive intestinal polypeptide was observed in the light period.

Glycine improves daytime sleepiness and fatigue induced by acute sleep restriction and enhances psychomotor vigilance. While it did not alter the circadian clock directly, glycine modulated SCN function by increasing certain neuropeptides, which may indirectly contribute to its beneficial effects on sleepiness and fatigue.

The study involved acute sleep restriction and did not observe direct alterations in the circadian clock itself, suggesting an indirect mechanism for glycine's effects on sleepiness and fatigue.


Evidence: mitochondrial fatty-acid transport

Acetyl-l-carnitine shows limited and potentially chance-driven benefits for global clinical impression in Alzheimer's disease, but no clear objective benefits for cognition or function.

Is Acetyl-l-carnitine (ALC) clinically effective in treating people with dementia?

Hypothesis: The efficacy of ALC in cognitive decline remains unclear, with early studies suggesting benefit and later, larger studies not supporting these findings.

This review identified 11 double-blind, randomized trials comparing ALC with placebo in people with Alzheimer's disease. Data were extracted and analyzed using Revman 4.1 software, primarily focusing on completers. Outcomes assessed included cognitive effects, severity of dementia, functional ability, and clinical global impression.

Statistically significant treatment effects favoring ALC were observed at 12 and 24 weeks for the number of patients showing improvement as determined by Clinical Global Impression (OR 2.33 at 12 weeks, OR 3.91 at 24 weeks). However, no benefit was found at 52 weeks for Clinical Global Impression, nor for cognition, severity of dementia, or functional ability when measured continuously. There were no statistically significant differences in adverse events between ALC and placebo groups.

There is some evidence for ALC's benefit on clinical global impression, but no evidence from objective assessments in other outcome areas. The statistically significant results might be due to chance given the number of comparisons. Currently, there is no evidence to recommend ALC's routine use in clinical practice for dementia.

All included trials focused only on Alzheimer's disease, not other types of dementia. Methodological differences and assessment tools varied widely across early and later studies, making comparisons difficult. The statistically significant findings for clinical global impression might be due to chance given the multiple comparisons. The review primarily used completers' data rather than intention-to-treat.


Evidence: brain-penetrant magnesium

A supplement containing magnesium L-threonate, phosphatidylserine, and vitamins C and D improved memory and cognition in healthy Chinese adults, with older individuals showing more benefit.

Does MagteinPS, a formulation containing magnesium L-threonate, phosphatidylserine, and vitamins C and D, improve cognitive function in healthy Chinese adults?

Hypothesis: MagteinPS will effectively raise magnesium levels in the brain and neurons, leading to improved memory and cognition.

This was a double-blind, placebo-controlled study involving 109 healthy Chinese adults aged 18-65 years. Participants were randomly assigned to receive either 2 g/day of MagteinPS or a placebo (starch) for 30 days. Cognitive function was assessed using "The Clinical Memory Test" before and after the supplementation period.

Subjects receiving MagteinPS showed significant improvements over the control group in all five subcategories of "The Clinical Memory Test" and in overall memory quotient scores. Older participants demonstrated greater improvement compared to younger participants.

MagteinPS significantly improved memory and cognition in healthy Chinese adults.


Evidence: anti-inflammatory long-chain PUFAs

Omega-3 supplements (LCn3) may slightly reduce coronary heart disease risk and triglycerides, while plant-based omega-3 (ALA) may slightly reduce overall cardiovascular events and arrhythmia.

What are the effects of increased intake of fish- and plant-based omega-3 fats (LCn3 and ALA) on all-cause mortality, cardiovascular events, adiposity, and lipids?

Hypothesis: Omega-3 polyunsaturated fatty acids from oily fish (LCn3) and plants (ALA) may benefit cardiovascular health.

This systematic review included 86 randomized controlled trials (RCTs) with 162,796 participants, lasting at least 12 months. Trials compared supplementation or advice to increase LCn3 or ALA intake versus usual or lower intake. Data were extracted and validity assessed by two independent reviewers, with separate random-effects meta-analyses for ALA and LCn3 interventions and meta-regression for dose-response relationships.

Increasing LCn3 had little or no effect on all-cause mortality (RR 0.97), cardiovascular mortality (RR 0.92), cardiovascular events (RR 0.96), stroke (RR 1.02), or arrhythmia (RR 0.99). It may slightly reduce coronary heart disease mortality (RR 0.90, NNTB 334) and coronary heart disease events (RR 0.91, NNTB 167). Increasing ALA intake probably made little or no difference to all-cause mortality (RR 1.01), cardiovascular mortality (RR 0.96), coronary heart disease mortality (RR 0.95), and coronary heart disease events (RR 1.00). Increased ALA may slightly reduce risk of cardiovascular disease events (NNTB 500) and probably slightly reduces risk of arrhythmia (RR 0.73, NNTB 91). Increasing LCn3 reduced triglycerides by approximately 15% in a dose-dependent manner.

Increasing LCn3 slightly reduces the risk of coronary heart disease mortality and events, and reduces serum triglycerides. Increasing ALA slightly reduces the risk of cardiovascular events and arrhythmia.

The certainty of evidence for some outcomes, such as coronary heart disease mortality and events for LCn3, and cardiovascular disease events and arrhythmia for ALA, was low to moderate. Most LCn3 evidence came from supplement trials, and there was little evidence regarding the effects of eating fish.