The human tri-peptide GHK and tissue remodeling.

The human peptide GHK and its copper complex GHK-Cu play a broad role in tissue repair and regeneration, with benefits for skin, hair, and various internal tissues.

What role does the human tri-peptide GHK and its copper complex GHK-Cu play in tissue remodeling?

Hypothesis: The human tri-peptide GHK and its copper complex GHK-Cu activate various processes involved in tissue remodeling, including cell chemoattraction, anti-inflammatory actions, protein synthesis, and cell proliferation.

This abstract reviews existing literature on the human peptide GHK and its copper complex GHK-Cu, summarizing their known biological activities related to tissue remodeling.

GHK and GHK-Cu activate several remodeling-related processes: chemoattraction of repair cells, anti-inflammatory actions (e.g., suppressing free radicals, increasing superoxide dismutase), increased protein synthesis (e.g., collagen, elastin), and increased proliferation of fibroblasts and keratinocytes, nerve outgrowth, angiogenesis, and hair follicle size. GHK-Cu has been shown to stimulate wound healing in various models and in humans. Controlled studies on aged skin demonstrated that GHK-Cu tightens skin, improves elasticity and firmness, reduces fine lines, wrinkles, photodamage, and hyperpigmentation. Additionally, GHK-Cu improves hair transplant success, protects hepatic tissue, blocks stomach ulcer development, and heals intestinal ulcers and bone tissue.

The human tri-peptide GHK and its copper complex GHK-Cu are involved in a wide array of biochemical processes that regulate tissue remodeling, demonstrating beneficial effects in wound healing, skin rejuvenation, and protection/healing of various tissues.

The abstract does not present new experimental data but rather summarizes existing findings, without providing specific details on study designs, sample sizes, or quantitative outcomes for many of the mentioned effects.


Randomized, placebo-controlled, double blind study on the clinical efficacy of a cream containing 5% alpha-lipoic acid related to photoageing of facial skin.

A 5% alpha-lipoic acid cream significantly reduced skin roughness and improved other signs of photoageing on facial skin over 12 weeks.

Does a cream containing 5% alpha-lipoic acid (LA) improve criteria associated with photoageing of facial skin compared to an identical cream without LA?

Hypothesis: A cream containing 5% LA will show beneficial effects on photoageing skin.

Thirty-three women, with a mean age of 54.4 years, participated in a randomized, placebo-controlled, double-blind study. For 12 weeks, half of each participant's face was treated twice daily with a 5% LA cream, and the other half with a control cream. Assessments included self-evaluation, clinical evaluation, photographic evaluation, and laser profilometry, with profilometry performed at the start and end of treatment.

All four assessment methods showed a statistically significant improvement on the LA-treated side of the face. Laser profilometry, the most objective method, showed an average decrease in skin roughness of 50.8% on the LA-treated side, compared to 40.7% on the placebo-treated side (P < 0.001).

Treatment for 12 weeks with a cream containing 5% LA improves clinical characteristics related to photoageing of facial skin.

The abstract does not explicitly state limitations of the study.


Indoor CO2 concentrations and cognitive function: A critical review.

Elevated indoor CO2 and poor ventilation can affect cognitive function, with pure CO2 impacting decision-making and reduced ventilation slowing cognitive speed.

What is the current understanding of the relationship between indoor CO2 concentrations and cognitive function?

Hypothesis: The review does not state a specific hypothesis, but rather aims to summarize existing findings regarding the cognitive impact of CO2.

This critical review summarized results from 37 experimental studies. These studies used objective cognitive tests and manipulated CO2 concentrations either by adding pure CO2 or by adjusting ventilation rates. A subset of these studies meeting objective criteria for strength and consistency was further analyzed.

Studies with varied designs suggested that both adding pure CO2 and adjusting ventilation rates can affect multiple cognitive functions. In a subset of strong and consistent studies, pure CO2 at common indoor concentrations only affected high-level decision-making in non-specialized populations, as measured by the Strategic Management Simulation battery. Lower ventilation and the accumulation of indoor pollutants, including CO2, were found to reduce the speed of various cognitive functions but did not affect accuracy.

While both pure CO2 and reduced ventilation (with accompanying pollutants) can impact cognitive function, the specific effects differ. Pure CO2 primarily affects high-level decision-making, whereas lower ventilation and pollutant accumulation tend to reduce cognitive speed without affecting accuracy. Inconsistencies in findings highlight the need for more standardized research methods.

Major confounding factors in the reviewed studies include variations in cognitive assessment methods, study designs, individual and populational differences among subjects, and uncertainties in exposure doses.


Exposure to Air Pollution in Rural Malawi: Impact of Cooking Methods on Blood Pressure and Peak Expiratory Flow.

Cooking outdoors with charcoal significantly reduces exposure to PM2.5 compared to cooking indoors with wood in rural Malawi, potentially mitigating respiratory symptoms.

What is the impact of different cooking methods (wood vs. charcoal) and locations (indoor vs. outdoor) on air pollution exposure, blood pressure, and peak expiratory flow in women in rural Malawi?

Hypothesis: The study implicitly hypothesizes that cooking with wood, especially indoors, will lead to higher PM2.5 exposure and potentially negative health outcomes compared to cooking with charcoal or outdoors.

The study used static and personal PM2.5 measurements with a miniature monitor (RTI MicroPEM) to characterize exposure among women cooking with wood and charcoal indoors and outdoors in rural Malawi. Blood pressure and peak expiratory flow rate (PEFR) were also measured.

Mean PM2.5 concentrations 1m from cookstoves were 1338 µg/m3 for wood and 31 µg/m3 for charcoal. Mean personal PM2.5 exposures were 706 µg/m3 for wood and 94 µg/m3 for charcoal. Personal indoor PM2.5 exposures were 3.3 times greater than outdoor for wood and 1.7 times greater for charcoal. Six out of eight participants had PEFR below 80% of expected prior to exposure. Reductions in PEFR were observed for participants cooking with wood indoors. Five out of eight participants reported breathing difficulties, coughing, and eye irritation when cooking with wood, with less severe symptoms for charcoal.

Exposure to PM2.5 was substantially reduced by cooking outdoors with charcoal. Simple interventions like cooking outside and minimizing time near stoves could reduce risks of respiratory and cardiovascular diseases.

The study involved a small number of participants (eight women) and did not explicitly state the duration of the exposure measurements or the follow-up period for health outcomes. It also noted that both wood and charcoal have negative environmental and health impacts.


Bladder cancer and exposure to water disinfection by-products through ingestion, bathing, showering, and swimming in pools.

Long-term exposure to trihalomethanes (THMs) from chlorinated water, through drinking, showering/bathing, and swimming, is associated with an increased risk of bladder cancer.

Is bladder cancer risk associated with exposure to trihalomethanes (THMs) through ingestion of water, and through inhalation and dermal absorption during showering, bathing, and swimming in pools?

Hypothesis: The authors hypothesized that bladder cancer risk would be associated with exposure to THMs through various routes, including ingestion, inhalation, and dermal absorption.

A case-control study was conducted in Spain between 1998 and 2001, involving 1,219 bladder cancer cases and 1,271 controls. Lifetime personal information on water consumption and water-related habits was collected and linked with THM levels in geographic study areas.

Long-term THM exposure was associated with a twofold bladder cancer risk, with an odds ratio of 2.10 for average household THM levels of >49 versus <=8 micro g/liter. Ingestion exposure of >35 micro g/day had an odds ratio of 1.35 compared to not drinking chlorinated water. The odds ratio for duration of shower or bath weighted by residential THM level was 1.83 for the highest compared with the lowest quartile. Swimming in pools was associated with an odds ratio of 1.57.

Bladder cancer risk was associated with long-term exposure to THMs in chlorinated water at levels commonly found in industrialized countries.

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


Evidence: adds magnesium and calcium

Many EU countries regulate drinking water hardness, calcium, or magnesium, but these regulations are inconsistent and often not based on current health research.

How do European Union countries regulate calcium and magnesium in drinking water, and is this regulation aligned with current scientific evidence regarding health impacts?

Hypothesis: The abstract does not explicitly state a hypothesis, but it implies that current regulations for calcium and magnesium in drinking water in EU countries may not adequately reflect scientific evidence on health effects.

The study involved a summary of the situation regarding drinking water quality regulations in 28 European Union countries, focusing on calcium and magnesium content or total hardness.

The current EU Drinking Water Directive does not include limits for hardness, calcium, or magnesium. However, 12 EU member states regulate these parameters through law, and 7 countries use technical guidance. Several countries also provide educational information to the public. The regulations across most countries are not based on current research and are not comparable, with some providing recommended ranges and others mandatory minimum or maximum limit values.

Current drinking water quality regulations in most EU countries regarding calcium and magnesium are not consistently based on up-to-date scientific research and lack comparability. This information is intended to aid in the implementation of the revised EU Directive.

The abstract does not explicitly state limitations of the study itself, but it highlights the limitation of current regulations not being based on current research.


Evidence: conductive Earth contact

Connecting with the Earth through grounding may influence inflammation, immune responses, and wound healing by altering white blood cell counts and inflammatory molecules.

What are the physiological and health effects of electrically conductive contact of the human body with the Earth's surface (grounding or earthing)?

Hypothesis: Grounding an organism produces measurable differences in the concentrations of white blood cells, cytokines, and other molecules involved in the inflammatory response, and can influence outcomes of studies on inflammation, wound healing, and tumorigenesis.

The report synthesizes multi-disciplinary research findings and presents several hypotheses based on current research results and understanding of electronic aspects of cell and tissue physiology, cell biology, biophysics, and biochemistry. It also references studies using delayed onset muscle soreness as an experimental injury to monitor immune responses under grounded versus ungrounded conditions.

Electrically conductive contact with the Earth produces intriguing effects on physiology and health, relating to inflammation, immune responses, wound healing, and prevention and treatment of chronic inflammatory and autoimmune diseases. Grounding reduces pain and alters the numbers of circulating neutrophils and lymphocytes, and affects various circulating chemical factors related to inflammation.

Grounding appears to offer a new perspective for studying inflammation and is an important, often overlooked, factor in experimental animal studies that can influence outcomes related to inflammation, wound healing, and tumorigenesis.

The report primarily informs researchers and alerts them to potential factors, rather than presenting new experimental data. It also highlights the need for researchers to consider the length of time and degree of grounding, implying these are often overlooked.


Evidence: tracks indoor relative humidity

Indoor relative humidity between 40-60% is associated with better COVID-19 outbreak outcomes compared to humidity levels outside this range.

Does indoor relative humidity modulate the spread and severity of COVID-19 outbreaks?

Hypothesis: Indoor climate, particularly relative humidity (RH), may be a more relevant modulator of COVID-19 outbreaks than outdoor conditions, with intermediate RH (40-60%) associated with better outcomes.

The study combined population-based COVID-19 statistics and meteorological measurements from 121 countries. Epidemiological data were rigorously processed to reduce bias. A computational workflow was developed and experimentally validated to estimate indoor conditions based on outdoor weather data and standard indoor comfort conditions.

The analysis showed robust and systematic relationships between regional COVID-19 outbreaks and indoor relative humidity. Specifically, intermediate RH (40-60%) was robustly associated with better COVID-19 outbreak outcomes compared to RH below 40% or above 60%.

Indoor conditions, particularly indoor relative humidity, modulate the spread and severity of COVID-19 outbreaks.


Evidence: bright light entrains circadian rhythm

Bright light therapy effectively reduces depression symptoms and increases treatment response rates in adults with seasonal affective disorder.

Is bright light therapy (BLT) effective in treating seasonal affective disorder (SAD) in adults?

Hypothesis: The study implicitly hypothesizes that bright light therapy (BLT) will be superior to placebo (dim light or sham/low-density negative ion generators) in treating seasonal affective disorder (SAD).

This meta-analysis systematically searched for randomized, single- or double-blind clinical trials comparing BLT (≥1,000 lx) against dim light (≤400 lx) or sham/low-density negative ion generators. Primary outcome was post-treatment depression score, and secondary was treatment response rate. Only first-period data from crossover trials were used.

Nineteen studies were included. BLT was superior to placebo for depression ratings with a standardized mean difference of -0.37 (95% CI: -0.63 to -0.12) across 18 studies (610 patients). For response to active treatment, BLT had a risk ratio of 1.42 (95% CI: 1.08-1.85) across 16 studies (559 patients). No publication bias was found, but moderate heterogeneity and a moderate-to-high risk of bias were noted.

Bright light therapy (BLT) is an effective treatment for seasonal affective disorder (SAD).

The available evidence comes from methodologically heterogeneous studies with small-to-medium sample sizes, and there was a moderate-to-high risk of bias.


Evidence: inhibits plasmin, reduces melanin

Tranexamic acid effectively treats melasma through various delivery methods, with oral TXA being most potent but having side effects, and topical TXA being well-tolerated.

What are the various delivery methods of tranexamic acid (TXA) for treating melasma, and how effective are they compared to traditional treatments?

Hypothesis: The study aims to characterize the efficacy of different TXA delivery methods for melasma treatment.

A comprehensive review of the literature was conducted using PubMed and Embase in May 2022. The search terms used were 'tranexamic acid' and 'melasma'. Forty-six articles were included in the review.

Oral, intralesional, and topical TXA were found to be safe and effective treatments for melasma, with overall improvement in MASI scores. Oral TXA was the most effective, particularly for refractory melasma, but was associated with gastrointestinal upset and menstrual irregularities. Intralesional injections and microneedling with topical TXA were effective alternatives. Topical TXA alone was the least effective but showed better tolerability than hydroquinone.

Tranexamic acid, delivered orally, intralesionally, or topically, is an effective treatment for melasma, with oral administration being the most potent despite side effects. Topical TXA is better tolerated than hydroquinone.

The pro-thrombotic nature of oral TXA must be considered before prescribing. The review did not specify the exact number of patients experiencing side effects or the specific MASI score improvements for each method.


Evidence: reduces nighttime noise exposure

Transportation noise, especially at night, significantly increases cardiovascular disease risk by disrupting sleep, elevating stress, and causing oxidative stress.

What are the indirect, nonauditory cardiovascular health effects of transportation noise?

Hypothesis: Transportation noise, particularly at night, increases cardiovascular morbidity and mortality by causing sleep fragmentation, elevated stress hormones, and increased oxidative stress, which can lead to vascular dysfunction, inflammation, and hypertension.

This review provides an updated overview of epidemiological research on transportation noise and cardiovascular risk factors and disease. It also includes mechanistic insights from clinical and experimental studies, discusses potential effects on vascular dysfunction, oxidative stress, and inflammation in humans and animals, and explains underlying pathomechanisms. Current and future noise mitigation strategies are also described.

Epidemiological studies show that transportation noise increases the risk for cardiovascular morbidity and mortality, with strong evidence for ischemic heart disease, heart failure, and stroke. Nighttime traffic noise leads to sleep fragmentation, shortened sleep, elevated stress hormones, and increased oxidative stress in the vasculature and brain. These factors promote vascular dysfunction, inflammation, and arterial hypertension, thereby increasing cardiovascular risk. The World Health Organization estimates that traffic-related noise in Western Europe results in at least 1.6 million healthy life years lost annually.

Transportation noise is a significant cardiovascular risk factor, primarily through indirect, nonauditory mechanisms involving sleep disruption, stress hormone elevation, and oxidative stress, leading to vascular dysfunction, inflammation, and hypertension.

The abstract does not explicitly state limitations of the review itself, but rather summarizes the existing evidence and mechanisms.


NAD metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized controlled trial

Nicotinamide Mononucleotide (NMN);NAD⁺ Activation Stack (NMN + Resveratrol + Pterostilbene)

NMN supplementation safely increased NAD metabolism in healthy middle-aged adults and showed a non-significant trend towards reducing arterial stiffness.

Does long-term nicotinamide mononucleotide (NMN) supplementation influence biochemical and metabolic health parameters, including NAD metabolism and arterial stiffness, in healthy middle-aged adults?

Hypothesis: The study implicitly hypothesized that NMN supplementation would prevent the reduction of NAD levels and potentially alleviate aging-related diseases, as observed in animal studies.

A 12-week randomized, double-blind, placebo-controlled, parallel-group clinical trial was conducted with 36 healthy middle-aged participants. Participants received either 125 mg NMN or placebo twice daily.

Serum nicotinamide levels were significantly higher in the NMN group compared to the placebo group. Pulse wave velocity, an indicator of arterial stiffness, tended to decrease in the NMN group, but this difference was not statistically significant between the two groups. NMN supplementation at 250 mg/day was well tolerated with no adverse events.

NMN supplementation safely and effectively elevated NAD metabolism in healthy middle-aged adults. While NMN showed potential in alleviating arterial stiffness, this effect was not statistically significant in this study.

The study noted that while arterial stiffness tended to decrease, no significant difference was found between the two groups, suggesting a potential limitation in statistical power or effect size for this specific outcome.


Regular Supplementation With Resveratrol Improves Bone Mineral Density in Postmenopausal Women: A Randomized, Placebo-Controlled Trial

Daily resveratrol supplementation may help slow bone loss in the spine and hip of postmenopausal women.

Can resveratrol supplementation improve bone health in postmenopausal women?

Hypothesis: Resveratrol supplementation will improve bone health in postmenopausal women, possibly through circulatory benefits in bone tissue, given its phytoestrogen properties and bone-protective effects observed in rodent models.

The RESHAW trial was a 24-month randomized, double-blind, placebo-controlled, two-period crossover intervention. Postmenopausal women received 75 mg of resveratrol twice daily or a placebo. The study evaluated effects on cognition, cerebrovascular function, bone health, cardiometabolic markers, and well-being.

After 12 months, resveratrol supplementation increased bone density in the lumbar spine by +0.016 g/cm and in the neck of the femur by +0.005 g/cm compared to placebo. This was accompanied by a 7.24% reduction in C-terminal telopeptide type-1 collagen levels. The femoral neck T-score improved by +0.070, reducing the 10-year probability of major and hip fracture risk. The bone-protective benefit was greater in women with poor bone health biomarker status and in those who supplemented with vitamin D plus calcium.

Regular supplementation with 75 mg of resveratrol twice daily has the potential to slow bone loss in the lumbar spine and femoral neck in postmenopausal women without overt osteoporosis.


Effects of Spermidine Supplementation on Cognition and Biomarkers in Older Adults With Subjective Cognitive Decline: A Randomized Clinical Trial

A 12-month daily spermidine supplement did not improve memory or biomarkers in older adults with subjective cognitive decline, though exploratory findings suggest possible benefits for verbal memory and inflammation.

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

Does longer-term spermidine supplementation affect memory performance and biomarkers in older adults with subjective cognitive decline?

Hypothesis: Spermidine supplementation will show beneficial effects on memory performance and biomarkers in older adults with subjective cognitive decline, based on prior animal studies and preliminary human evidence.

This was a 12-month randomized, double-masked, placebo-controlled phase 2b trial (SmartAge trial) conducted at a single academic clinical research center in Germany. One hundred participants aged 60 to 90 years with subjective cognitive decline were randomly assigned (1:1) to receive either 0.9 mg/d of a spermidine-rich wheat germ extract or placebo (microcrystalline cellulose). The primary outcome was the change in mnemonic discrimination performance from baseline to 12 months, assessed by the Mnemonic Similarity Task. Secondary outcomes included other neuropsychological, behavioral, and physiological parameters, with safety also assessed.

A total of 100 participants (51 in the spermidine group, 49 in the placebo group; mean age 69 years; 49% female) were included in the analysis. Over 12 months, no significant changes were observed in mnemonic discrimination performance (between-group difference, -0.03; 95% CI, -0.11 to 0.05; P = .47) or secondary outcomes. Exploratory analyses suggested possible beneficial effects on inflammation and verbal memory. Adverse events were balanced between the groups.

Longer-term spermidine supplementation (0.9 mg/d) did not significantly improve memory or biomarkers in older adults with subjective cognitive decline compared to placebo. Exploratory findings on verbal memory and inflammation require validation in future studies, potentially with higher dosages.

The study was a monocenter trial, and the dosage of spermidine (0.9 mg/d) might have been insufficient to elicit significant effects. The observed beneficial effects on verbal memory and inflammation were exploratory and require further validation.


Rejuvant, a potential life-extending compound formulation with alpha-ketoglutarate and vitamins, conferred an average 8 year reduction in biological aging

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

A supplement called Rejuvant® was associated with an average 8-year reduction in biological age in a small study.

Can Rejuvant®, an alpha-ketoglutarate based formulation, reduce biological aging in humans?

Hypothesis: The researchers hypothesized that Rejuvant® could delay and/or reverse biological aging, extending healthspan and lifespan.

This was a retrospective analysis of DNA methylation age in 42 individuals. Participants took Rejuvant® for an average of 7 months. DNA methylation testing was performed at baseline and at the end of the treatment period.

Individuals showed an average decrease in biological aging of 8 years. A large majority of participants experienced a decrease in their biological age. Rejuvant® appeared to offer additional benefits to chronologically and biologically older individuals.

Rejuvant® is an intriguing candidate to affect human aging, demonstrating a nearly 8-year reversal in biological age in individuals taking it for 4 to 10 months. Further testing, especially in a placebo-controlled design, is required.

The study was a retrospective analysis and lacked a placebo-controlled design, which is noted as a requirement for continued testing.


The Effect of Berberine Supplementation on Glycemic Control and Inflammatory Biomarkers in Metabolic Disorders: An Umbrella Meta-analysis

Berberine supplementation may help improve blood sugar control and reduce inflammation in adults with metabolic disorders.

Does berberine supplementation improve glycemic control and inflammatory biomarkers in individuals with metabolic disorders?

Hypothesis: The study aimed to clarify inconsistent findings from previous meta-analyses regarding berberine's effects on glycemic parameters and inflammatory markers.

This umbrella meta-analysis systematically searched PubMed, Embase, Web of Science, Scopus, and Google Scholar for relevant meta-analyses published up to April 2023.

Berberine supplementation significantly reduced fasting blood glucose (ES: -0.77 and -0.65), hemoglobin A1C (ES: -0.57), HOMA-IR (ES: -1.04 and -0.71), insulin (ES: -1.00 and -0.63), IL-6 (ES: -1.23), TNF-α (ES: -1.04), and CRP (ES: -0.62 and -1.70).

Berberine supplementation appears effective in improving glycemic parameters and inflammatory markers in adults.

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


Efficacy of vitamin D supplementation on cancer mortality: systematic review and individual patient data meta-analysis

Vitamin D3 (Cholecalciferol);Targeted Organ-Support Nutrients

Daily vitamin D supplementation may reduce cancer mortality, but bolus dosing does not show the same benefit.

no-difference-cue: "did not significantly reduce" | favorable-cue: "reduction in cancer mortality"

Does vitamin D supplementation affect cancer mortality in the general population and prognosis in cancer patients?

Hypothesis: The study aims to evaluate the effect of vitamin D supplementation on cancer mortality and prognosis.

A systematic review and meta-analysis of 14 randomized, placebo-controlled trials (RCTs) with 104,727 participants (2015 cancer deaths) was conducted. Individual patient data (IPD) from 7 RCTs (94,068 participants) were also analyzed. Subgroup analyses were performed based on dosing regimen (daily vs. bolus) and other factors like age, sex, BMI, ethnicity, baseline vitamin D, adherence, and cancer-related factors.

The main meta-analysis of 14 RCTs showed a non-significant 6% reduction in cancer mortality (RR: 0.94 [0.86-1.02]). Subgroup analysis revealed a 12% lower cancer mortality in trials with a daily dosing regimen (RR: 0.88 [0.78-0.98]), but no reduction in trials using a bolus regimen (RR: 1.07 [0.91-1.24]). The IPD meta-analysis confirmed the overall finding (RR: 0.93 [0.84; 1.02]). Post-hoc analysis of daily dosing trials suggested adults aged ">= 70 years (RR: 0.83 [0.77; 0.98]) and subjects initiating vitamin D before cancer diagnosis (RR: 0.87 [0.69; 0.99]) benefited most. Data on baseline 25-hydroxyvitamin D levels and non-Hispanic White adults were insufficient.

Overall, vitamin D supplementation did not significantly reduce cancer mortality in the main meta-analysis. However, daily vitamin D administration, unlike bolus supplementation, was associated with a 12% reduction in cancer mortality.

The study noted insufficient data on baseline 25-hydroxyvitamin D levels and limited inclusion of non-Hispanic White adults in the trials, which prevented drawing conclusions for these subgroups.


A Collagen Supplement Improves Skin Hydration, Elasticity, Roughness, and Density: a Randomized, Placebo-Controlled, Blind Study

A collagen-based drinkable supplement improved several objective measures of skin health and aging in women over 35.

Does a drinkable nutraceutical containing collagen peptides and other micronutrients improve skin aging and skin health parameters?

Hypothesis: The drinkable nutraceutical ELASTEN will improve skin hydration, elasticity, roughness, and density compared to a placebo.

This was a randomized, placebo-controlled, blind study involving 72 healthy women aged 35 years or older. Participants were divided into two groups: 36 received the nutraceutical (2.5 g collagen peptides, acerola fruit extract, vitamin C, zinc, biotin, vitamin E complex) and 36 received a placebo for twelve weeks. Skin assessments were performed using corneometry for hydration, cutometry for elasticity, silicon skin replicas with PRIMOS for roughness, and skin sonography for density. The verum group was followed for an additional four weeks without the product to assess the sustainability of effects.

The test product significantly improved skin hydration, elasticity, roughness, and density. Statistically significant differences were observed between the verum group and the placebo group for all tested parameters. These positive effects were largely retained during the four-week follow-up period. Subjective assessments by participants were consistent with the measured effects, and the nutraceutical was well tolerated.

The drinkable nutraceutical ELASTEN significantly improves objective parameters of skin aging and health, including hydration, elasticity, roughness, and density, with sustained effects after product cessation.


GlyNAC supplementation in older adults improves glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation and insulin resistance

All-in-One Longevity Formulation;Glutathione;Glycine Powder;GlyNAC (Glycine + N-Acetylcysteine)

GlyNAC supplementation in older adults improved several markers of aging and health, but these benefits decreased after stopping the supplement.

What are the effects of GlyNAC supplementation and withdrawal on various health markers in older adults, including glutathione levels, oxidative stress, mitochondrial function, inflammation, and insulin resistance?

Hypothesis: GlyNAC supplementation in older adults will improve naturally-occurring glutathione deficiency, mitochondrial impairment, oxidative stress, and insulin resistance, similar to observations in aged mice.

This was a 36-week open-label pilot clinical trial involving eight older adults (OAs) and eight young adults (YAs). All participants underwent an initial pre-supplementation study. YAs were then released, while OAs received GlyNAC supplementation for 24 weeks, followed by a 12-week GlyNAC withdrawal period. Measurements included red blood cell (RBC) glutathione, mitochondrial fuel-oxidation (MFO), plasma biomarkers for oxidative stress, inflammation, endothelial function, glucose, and insulin, as well as gait speed, grip strength, 6-minute walk test, cognitive tests, genomic damage, glucose production and muscle protein breakdown rates, and body composition.

GlyNAC supplementation for 24 weeks in older adults corrected RBC-GSH deficiency, oxidative stress, and mitochondrial dysfunction. It also improved inflammation, endothelial dysfunction, insulin resistance, genomic damage, cognition, strength, gait speed, and exercise capacity, while lowering body fat and waist circumference. However, these benefits declined after stopping GlyNAC supplementation for 12 weeks.

GlyNAC supplementation for 24 weeks in older adults was well tolerated and demonstrated improvements across multiple health parameters, including reduced oxidative stress, corrected glutathione deficiency, improved mitochondrial function, decreased inflammation, insulin resistance, endothelial dysfunction, and genomic damage, as well as enhanced strength, gait speed, cognition, and body composition. These findings suggest GlyNAC could be a simple and viable method to promote health in aging humans, warranting further investigation.

This was a pilot trial with a small sample size (eight older adults) and an open-label design, which may limit the generalizability and strength of the findings.


Leukocyte telomere length, cancer incidence and all-cause mortality among Chinese adults

Longer telomeres are linked to a higher risk of cancer but a lower risk of non-cancer related death in Chinese adults.

unfavorable-cue: "increased risk" | favorable-cue: "reduced risk"

What is the association between leukocyte telomere length and the risk of cancer incidence and all-cause mortality in a large prospective cohort of Chinese adults?

Hypothesis: The study aims to investigate the association of leukocyte telomere length with risk of cancer incidence and all-cause mortality.

Relative telomere lengths were quantified using quantitative real-time PCR in genomic DNA from peripheral blood samples of 26,540 middle-aged or older Chinese adults. Hazard ratios (HRs) and 95% confidence intervals (CIs) for cancer and deaths by quintiles of telomere length were calculated using Cox proportional hazards regression, adjusted for age, sex, and other potential confounders.

After baseline, 4,353 persons developed cancer and 7,609 died. Participants with the longest decile of telomeres had a 26% higher risk of total cancer incidence compared to the shortest decile. Longer telomeres were associated with a lower risk of all-cause mortality (HR = 0.93), noncancer death (HR = 0.81), and specifically, death from chronic obstructive pulmonary disease and pneumonia (HR = 0.79) and digestive diseases (HR = 0.60).

Longer telomeres are associated with an increased risk of overall cancer development and several specific cancer types, but also with a reduced risk of noncancer-related death.


DNA methylation GrimAge strongly predicts lifespan and healthspan

Epigenetic Age (DNA-Methylation Clock) Testing;Comprehensive Blood-Biomarker Testing

A new DNA methylation-based biomarker, DNAm GrimAge, accurately predicts lifespan and various age-related health conditions.

Can plasma protein levels be estimated using DNA methylation (DNAm) levels, and can these estimates be combined into a robust predictor of lifespan?

Hypothesis: The study implicitly hypothesizes that DNAm levels can be used to estimate plasma protein levels, and that these estimates, along with other DNAm-based factors, can form a powerful predictor of lifespan and healthspan.

The researchers developed seven DNAm-based estimators for plasma proteins, including plasminogen activator inhibitor 1 (PAI-1) and growth differentiation factor 15. These estimators, along with a DNAm-based estimator of smoking pack-years, were consolidated into a composite biomarker called DNAm GrimAge. They also created AgeAccelGrim by adjusting DNAm GrimAge for chronological age. The predictive ability of DNAm GrimAge and AgeAccelGrim was validated using large-scale data from thousands of individuals.

DNAm GrimAge strongly predicted time-to-death (P=2.0E-75), time-to-coronary heart disease (P=6.2E-24), and time-to-cancer (P=1.3E-12). It also showed a strong relationship with fatty liver/excess visceral fat from CT data and age-at-menopause (P=1.6E-12). AgeAccelGrim was significantly associated with comorbidity count (P=3.45E-17). Age-adjusted DNAm PAI-1 levels were associated with lifespan (P=5.4E-28), comorbidity count (P=7.3E-56), and type 2 diabetes (P=2.0E-26). These biomarkers also showed expected relationships with healthy diet and educational attainment.

DNAm GrimAge and its components are powerful epigenetic biomarkers that strongly predict lifespan and healthspan, outperforming existing epigenetic clocks. These biomarkers are expected to have applications in human anti-aging research.


The Gut Microbiome, Aging, and Longevity: A Systematic Review

The gut microbiome changes significantly with age, showing higher diversity and specific functional shifts in older adults, especially the oldest-old.

What are the aging-associated alterations in the diversity, composition, and functional features of the gut microbiota?

Hypothesis: The gut microbiome undergoes extensive changes across the lifespan, and age-related processes may influence the gut microbiota and its related metabolic alterations.

This systematic review identified 27 empirical human studies focusing on normal and successful aging to summarize current literature on age-related changes in gut microbiota diversity, composition, and functional features.

Alpha diversity of microbial taxa, functional pathways, and metabolites was higher in older adults, especially the oldest-old, compared to younger individuals. Beta diversity distances significantly differed across developmental stages and between oldest-old and younger-old adults. Older adults showed reduced pathways for carbohydrate metabolism and amino acid synthesis. Oldest-old adults had functional differences, including greater potential for short-chain fatty acid production and increased butyrate derivatives, compared to young-old adults.

Older adults, particularly the oldest-old, exhibit distinct gut microbiota characteristics, including higher alpha diversity and specific functional differences like increased short-chain fatty acid production, which may offer insights into age-related processes.

A definitive interpretation of the findings is limited by the cross-sectional design of the published reports included in the review.


Complications of Diabetes and Metrics of Glycemic Management Derived From Continuous Glucose Monitoring

Continuous glucose monitoring metrics, especially Time in Range, are associated with diabetes complications and may offer better insights than HbA1c alone.

What is the relationship between continuous glucose monitoring (CGM)-derived metrics of glycemic variability and diabetes-related complications?

Hypothesis: The study implicitly hypothesizes that CGM-derived metrics, beyond HbA1c, are associated with diabetes complications and can provide insight into short-term glucose fluctuations.

A systematic review was conducted by searching PubMed and Embase databases from January 1, 2010, to August 22, 2020. The search terms included 'type 1 diabetes', 'type 2 diabetes', 'diabetes-related microvascular and macrovascular complications', and 'measures of glycaemic variability'. Studies not using CGM or involving non-diabetic, acutely unwell, pregnant participants, or those using insulin pumps were excluded. The final review included 34 publications out of 1636 identified records, encompassing 20852 participants (663 with T1D and 19909 with T2D).

Glycemic variability and low time in range (TIR) were associated with all studied microvascular and macrovascular complications of diabetes. Higher TIR was specifically linked to a reduced risk of albuminuria, retinopathy, cardiovascular disease mortality, all-cause mortality, and abnormal carotid intima-media thickness. Peripheral neuropathy was primarily associated with the standard deviation of blood glucose levels (SD) and mean amplitude of glycemic excursions (MAGE).

The evidence supports an association between diabetes complications and CGM-derived measures of intraday glycemic variability. Time in range (TIR) was the most consistent measure, suggesting its growing importance in clinical practice.

More longitudinal studies and trials are needed to confirm these associations, especially for type 1 diabetes, where data are limited.


Heart Rate Variability and Risk of All-Cause Death and Cardiovascular Events in Patients With Cardiovascular Disease: A Meta-Analysis

Biometric Wearables (Sleep, HRV & Recovery);Heart-Rate-Variability & Autonomic Tools

Lower heart rate variability is linked to a higher risk of death and cardiovascular problems in people with heart disease.

What is the association between heart rate variability (HRV) and the risk of all-cause death or cardiovascular events in patients with cardiovascular disease (CVD)?

Hypothesis: Lower heart rate variability (HRV) is associated with a higher risk of cardiovascular events and mortality.

A meta-analysis of 28 cohort studies involving 3,094 participants was conducted. Four databases (PubMed, MEDLINE, Embase, and Cochrane Central Register of Controlled Trials) were searched to extract adjusted hazard ratios (HR) from eligible studies with a follow-up of at least 1 year.

Lower HRV was associated with a higher risk of all-cause death (pooled HR 2.27, 95% CI: 1.72, 3.00) and cardiovascular events (pooled HR 1.41, 95% CI: 1.16, 1.72). Subgroup analysis showed a significant pooled HR for all-cause death in patients with acute myocardial infarction (AMI) but not heart failure. For cardiovascular events, the pooled HR was significant for patients with AMI and acute coronary syndrome, but not for those with coronary artery disease and heart failure. Both time and frequency domains of HRV were significantly associated with risk.

Lower heart rate variability is significantly associated with an increased risk of all-cause death and cardiovascular events in patients with cardiovascular disease, particularly in those with acute myocardial infarction and acute coronary syndrome.

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


Sauna use as a lifestyle practice to extend healthspan

Contrast Therapy Systems (Sauna + Cold + Light);Infrared & Traditional Saunas

Regular sauna use may improve health and longevity by inducing beneficial physiological adaptations to heat.

What are the physiological responses and health benefits associated with sauna use, and how might it extend healthspan?

Hypothesis: Repeated sauna use, through mild hyperthermia and thermoregulatory responses, may optimize the body's response to heat and extend healthspan.

This is a review article that synthesizes findings from observational, interventional, and mechanistic studies on sauna use. It describes sauna practices, physiological responses to heat stress, molecular mechanisms, health benefits, and concerns.

Sauna use involves short-term passive exposure to high temperatures (45 °C to 100 °C), inducing mild hyperthermia and a thermoregulatory response involving neuroendocrine, cardiovascular, and cytoprotective mechanisms. Repeated use acclimates the body to heat, likely via hormesis. Large prospective cohort studies show strong dose-dependent links between sauna use and reduced morbidity and mortality.

Sauna use appears to be a probable means to extend healthspan by eliciting beneficial physiological and molecular responses, as supported by various studies showing reduced morbidity and mortality.

This review article does not present new experimental data but rather summarizes existing research. Specific limitations of the reviewed studies are not detailed in the abstract.


Effect of Repeated Low-Level Red-Light Therapy for Myopia Control in Children: a Multicenter Randomized Controlled Trial

Photobiomodulation (Red & Near-Infrared Light)

Repeated low-level red-light therapy significantly slows myopia progression in children with no observed adverse effects.

Does repeated low-level red-light (RLRL) therapy effectively and safely control myopia progression in children?

Hypothesis: The study implicitly hypothesized that RLRL therapy would be more effective than single-vision spectacles (SVS) alone in controlling myopia progression in children, as measured by changes in axial length and spherical equivalent refraction (SER), without significant adverse events.

This was a multicenter, randomized, parallel-group, single-blind clinical trial involving 264 children aged 8 to 13 with myopia. Participants were randomized to either the intervention group (RLRL treatment plus SVS) or the control group (SVS only). RLRL therapy involved a desktop device emitting 650-nm red light for 3 minutes per session, twice daily, 5 days per week, administered at home. Primary outcomes were changes in axial length and SER measured over 12 months.

Among 246 children analyzed, the 12-month axial elongation was 0.13 mm for the RLRL group and 0.38 mm for the SVS group. SER progression was -0.20 D for the RLRL group and -0.79 D for the SVS group. The differences between groups were 0.26 mm in axial elongation and -0.59 D in SER progression, favoring the RLRL group. No severe adverse events, functional visual loss, or structural damage were observed.

Repeated low-level red-light therapy is a promising alternative treatment for myopia control in children, demonstrating good user acceptability and no documented functional or structural damage.

The abstract does not explicitly state limitations of the study.


Effects of Organic Light-Emitting Diodes on Circadian Rhythm and Sleep

Blue-Light Management & Circadian Lighting

OLED light at 3,000 K may be slightly less disruptive to deep sleep and late-night melatonin levels than LED light at the same color temperature.

Do OLED and LED lights at a color temperature of 3,000 K differentially affect melatonin profile, sleep, and vigilance compared to dim light?

Hypothesis: The study investigates the effects of OLED and LED at 3,000 K on melatonin, sleep, and vigilance, following previous findings that OLED at 4,000 K caused less melatonin phase delay than LED.

Twenty-four healthy subjects (27.5±5.1 years) were exposed to OLED, LED, or dim light (DL) from 17:30 to 24:00 in a randomized order with a 1-week interval. Saliva samples were collected hourly from 18:00 to 24:00 for melatonin analysis. Polysomnography (PSG) and a psychomotor vigilance test (PVT) were also conducted.

Melatonin onset time was significantly delayed by both OLED and LED compared to DL, with no significant difference between OLED and LED. The mean melatonin level at 24:00 was lower under LED than DL, but there was no significant difference between OLED and DL. The percentage of slow wave sleep (N3) was significantly lower in LED than in OLED.

Evening light exposure can suppress late-night melatonin secretion and disturb deep sleep, with these effects being slightly worse under LED than OLED at a color temperature of 3,000 K.

The study design involved a specific exposure duration (17:30 to 24:00) and a single color temperature (3,000 K), which may limit generalizability to other light conditions or durations.


Long-term exposure to air pollution and mortality in Scotland: a register-based individual-level longitudinal study

Long-term exposure to common air pollutants is linked to increased mortality from various physical and mental health conditions.

What is the association between long-term exposure to multiple ambient air pollutants and all-cause and cause-specific mortality from both physical and mental illnesses?

Hypothesis: The study implicitly hypothesizes that long-term exposure to air pollutants is associated with increased all-cause and cause-specific mortality, including mental/behavioral health outcomes.

This study used individual-level administrative data from the Scottish Longitudinal Study (SLS) for 202,237 individuals aged 17 and older, followed between 2002 and 2017. The SLS dataset was linked to annual concentrations of NO2, SO2, PM10, and PM2.5 pollution at 1 km2 spatial resolution using residential postcodes. Survival analysis was applied to assess the association between air pollution and all-cause, cardiovascular, respiratory, cancer, mental/behavioral disorders/suicides, and other-causes mortality.

Higher all-cause mortality was associated with increasing concentrations of PM2.5, PM10, NO2, and SO2. NO2, PM10, and PM2.5 were also associated with cardiovascular, respiratory, cancer, and other-causes mortality. Specifically, the mortality hazard from respiratory diseases increased by 1.062 per 1 μg/m3 increase in PM2.5, 1.025 per 1 μg/m3 increase in PM10, and 1.013 per 1 μg/m3 increase in NO2. Mortality from mental and behavioral disorders was associated with a 1.042 higher hazard per 1 μg/m3 increase in SO2.

The study revealed an association between long-term (16-year) exposure to ambient air pollution and all-cause and cause-specific mortality. The results suggest that policies and interventions to enhance air quality could reduce mortality from cardio-respiratory, cancer, and mental/behavioral disorders in the long term.


Drinking water source and exposure to regulated water contaminants in the California Teachers Study cohort

Water Purification (Reverse Osmosis & Ultrafiltration)

Even with average contaminant levels below regulatory limits, drinking water exposures vary significantly among California women based on their demographics and neighborhood characteristics.

What are the drinking water sources and exposures to regulated water contaminants among participants in the California Teachers Study cohort?

Hypothesis: The study implicitly hypothesizes that there may be variations in drinking water sources and contaminant exposures across different demographic and neighborhood subgroups within the California Teachers Study cohort, even if average levels are below regulatory limits.

The study linked geocoded addresses of 115,206 California Teachers Study participants (1995-1996) to Community Water System (CWS) service area boundaries and monitoring data. Average concentrations (1990-2015) of arsenic, uranium, nitrate, gross alpha (GA), five haloacetic acids (HAA5), total trihalomethanes (TTHM), trichloroethylene (TCE), and tetrachloroethylene (PCE) were computed. Generalized linear regression was used to estimate geometric mean ratios of CWS exposures across demographic subgroups and neighborhood characteristics. Self-reported drinking water source and consumption from a 2017-2019 follow-up were also described.

Medians of average concentrations for all contaminants were below regulatory limits. For example, arsenic was 1.03 µg/L, uranium 3.48 µg/L, GA 2.21 pCi/L, nitrate 0.54 mg/L, HAA5 8.67 µg/L, and TTHM 12.86 µg/L. Among participants who lived within a CWS boundary and reported their water source (2017-2019), approximately 74% reported municipal, 15% bottled, 2% private well, 4% other, and 5% did not know/missing. Black, Hispanic, and Native American participants had higher average arsenic, uranium, GA, and nitrate concentrations compared to non-Hispanic white participants. Participants in higher socioeconomic status (SES) quartiles had lower arsenic, uranium, GA, and nitrate, but higher HAA5 and TTHM. Non-metropolitan participants had higher arsenic, uranium, and nitrate, while metropolitan participants had higher HAA5 and TTHM.

While average water contaminant levels were generally below regulatory limits in this large cohort of California women, significant heterogeneity in exposures was observed across sociodemographic subgroups and neighborhood characteristics. These data will be used for future assessments of drinking water exposures and disease risk.

The abstract does not explicitly state limitations, but it implies that the study focuses on describing exposures and will be used for future assessments, suggesting it is not a health outcomes study itself.


Self-Reported Sleep Duration and Quality and Cardiovascular Disease and Mortality: A Dose-Response Meta-Analysis

Sleep Optimization & Circadian Systems;Nasal-Breathing Sleep Tape

Sleeping more than 8 hours per night is linked to an increased risk of death and cardiovascular problems.

What is the association between self-reported sleep duration and quality and the risk of cardiovascular disease and mortality?

Hypothesis: The study hypothesized that sleep duration and quality may be associated with cardiovascular harm and mortality.

A systematic review, meta-analysis, and spline analysis of prospective cohort studies were conducted. Data from identified studies in MEDLINE and EMBASE were extracted. Linear and nonlinear dose-response meta-analysis models, along with DerSimonian-Laird random-effects models of risk ratios, were used to analyze the data.

Seventy-four studies with 3,340,684 participants were reviewed. Self-reported sleep duration >8 hours was associated with an increased risk of all-cause mortality: 1.14 for 9 hours, 1.30 for 10 hours, and 1.47 for 11 hours. No significant difference was found for sleep <7 hours, and similar patterns were observed for stroke and cardiovascular disease mortality. Subjective poor sleep quality was associated with coronary heart disease (risk ratio 1.44) but not with mortality or other outcomes.

Divergence from the recommended 7 to 8 hours of sleep is associated with a higher risk of mortality and cardiovascular events. Longer sleep durations may be more strongly associated with adverse outcomes compared to shorter sleep durations.


Senolytic drugs: from discovery to translation

All-in-One Longevity Formulation;Fisetin Senolytic Capsules;Quercetin Capsules

Senolytic drugs, which clear aging cells, show promise in preclinical studies for treating many age-related diseases, with human trials currently underway.

What are senolytic drugs and what is their potential for treating age-related dysfunction and diseases?

Hypothesis: Senolytic drugs, by selectively clearing senescent cells, can delay, prevent, or alleviate various age-related disorders and conditions.

This abstract reviews the discovery of senolytic drugs and summarizes findings from preclinical models and early pilot human trials.

The first senolytic drugs (Dasatinib, Quercetin, Fisetin, Navitoclax) were discovered using a hypothesis-driven approach. In preclinical models, senolytics alleviated over 40 conditions, including frailty, cancers, and various organ system disorders. Early human pilot trials suggest senolytics decrease senescent cells, reduce inflammation, and alleviate frailty.

Senolytics show promise in preclinical models for treating numerous age-related conditions by targeting senescent cells. Early human trials are encouraging, but more extensive clinical trials are needed before widespread use.

The abstract notes that it is too early for senolytics to be used outside of clinical trials, indicating that current human data are preliminary and further research is required.


Cellular Senescence: A Translational Perspective

Targeting senescent cells with senolytic drugs shows promise for treating age-related diseases and chronic conditions by removing harmful cells.

unfavorable-cue: "harmful" | favorable-cue: "alleviating"

The abstract does not explicitly state a question, but it investigates the role of cellular senescence in aging and chronic diseases and the potential for therapeutic intervention.

Hypothesis: The abstract implies a hypothesis that targeting senescent cells by inhibiting their pro-survival pathways (SCAPs) could alleviate senescence-associated conditions.

The authors used a hypothesis-driven approach to discover Senescent Cell Anti-apoptotic Pathways (SCAPs) and subsequently identified senolytic agents based on these pathways. These agents were then tested in pre-clinical models.

Senescent cells accumulate with aging and in chronic diseases, contributing to inflammation, metabolic dysregulation, and other pathologies through the SASP. Delaying or reducing senescent cell burden is linked to improved outcomes. The discovery of SCAPs led to the identification of senolytic agents that alleviate multiple senescence-related phenotypes in pre-clinical models.

Cellular senescence plays a significant role in aging and chronic diseases. Senolytic agents, which target SCAPs and induce senescent cell apoptosis, show promise in pre-clinical models for alleviating senescence-related conditions and are being translated into clinical interventions.

The abstract does not explicitly state limitations of the study. It mentions that senolytic agents are 'beginning the process of being translated into clinical interventions,' implying that human clinical data is still emerging or not yet available.


Effect of Urolithin A Supplementation on Muscle Endurance and Mitochondrial Health in Older Adults: A Randomized Clinical Trial

Urolithin A (Mitopure);Pomegranate Ellagitannin Extract

Daily urolithin A supplementation improved muscle endurance and certain cellular health biomarkers in older adults, but did not significantly impact walking distance or maximal ATP production.

no-difference-cue: "did not significantly improve" | favorable-cue: "improved muscle"

Does oral urolithin A supplementation improve 6-minute walk distance, muscle endurance, and biomarkers of mitochondrial and cellular health in older adults?

Hypothesis: Urolithin A, a natural gut microbiome-derived metabolite, will improve muscle function and mitochondrial health in older adults, based on its known effects in animals and its ability to induce mitochondrial gene expression in humans.

This was a double-blind, placebo-controlled randomized clinical trial involving 66 adults aged 65 to 90 years. Participants were randomized to receive either 1000 mg daily oral urolithin A or placebo for 4 months. Muscle fatigue tests and plasma biomarker analysis were conducted at baseline, 2 months, and 4 months. Six-minute walk distance and maximal ATP production were assessed at baseline and 4 months. An intention-to-treat approach was used for analysis.

Urolithin A significantly improved muscle endurance in the first dorsal interosseus (FDI) and tibialis anterior (TA) muscles at 2 months compared to placebo. Plasma levels of several acylcarnitines, ceramides, and C-reactive protein decreased with urolithin A at 4 months compared to placebo. There was no significant improvement in the 6-minute walk distance or maximal ATP production in the hand muscle with urolithin A supplementation compared to placebo. No statistical differences in adverse events were observed between the groups.

Urolithin A supplementation was safe and well tolerated. While it did not significantly improve 6-minute walk distance or maximal ATP production, it did improve muscle endurance and plasma biomarkers, suggesting a potential to counteract age-associated muscle decline. Further research is needed to confirm these findings.

The study did not find significant improvements in primary endpoints like 6-minute walk distance and maximal ATP production, indicating that the observed benefits might be limited or require further investigation.


Evaluating the Impact of Urolithin A Supplementation on Running Performance, Recovery, and Mitochondrial Biomarkers

Urolithin A supplementation may aid recovery and improve aerobic capacity in male endurance runners, but it did not directly enhance running performance in this study.

Does Urolithin A (UA) supplementation improve running performance, recovery, and mitochondrial biomarkers in competitive male distance runners?

Hypothesis: UA supplementation will improve muscle strength, endurance, and mitochondrial health biomarkers, suggesting it may be an effective ergogenic aid in competitive male distance runners.

This was a double-blind, parallel-group, placebo-controlled clinical trial. 42 competitive male distance runners (27.2 ± 1.0 years) were randomized to receive either 1000 mg/day UA (n = 22) or placebo (n = 20) for 4 weeks during an altitude training camp. Physiological outcomes, including body composition, hemoglobin mass, running economy, and maximal aerobic capacity, were measured at baseline and after 4 weeks. Weekly downhill running bouts were performed, with capillary blood samples collected to assess inflammation (CRP) and muscle damage (CK). A subset of athletes completed a 3000 m time trial (n = 11 PL, n = 11 UA) or had skeletal muscle biopsies (n = 9 PL, n = 11 UA) pre/post supplementation to assess performance and explore muscle proteome and mitochondrial function.

Running performance (3000 m time trial) was not significantly improved in either group (UA: p = 0.116, PL: p = 0.771). However, UA supplementation significantly lowered ratings of perceived exertion (RPE, p = 0.02) and reduced indirect markers of post-exercise muscle damage (CK, total area under the curve p < 0.0001) following the 3000 m time trial compared with placebo. While there was no statistically significant time × treatment interaction for aerobic capacity (p = 0.138), UA supplementation showed a large within-group increase in maximal aerobic capacity (5.4 ± 0.9%, p = 0.009), compared to a smaller increase in the PL group (3.6 ± 1.3%, p = 0.098). Proteomic screening revealed UA upregulated mitochondrial pathways and downregulated inflammatory pathways, and led to a medium effect for increased markers of mitophagy without changes in mitochondrial function.

Four weeks of daily UA supplementation facilitates recovery by downregulating inflammatory pathways and indirect markers of muscle damage. Despite reductions in perceived exertion and increased aerobic capacity, UA supplementation did not further enhance performance in highly trained male endurance athletes.

The study did not find a statistically significant improvement in 3000m running performance or a significant time x treatment interaction for aerobic capacity, despite some positive within-group changes and effects on recovery markers.


Sulforaphane, found in broccoli sprouts, may help manage type 2 diabetes by reducing liver glucose production and improving blood sugar control.

Can gene expression profiling identify clinically relevant treatment options for type 2 diabetes?

Hypothesis: Sulforaphane, identified through gene expression profiling, may reverse the disease signature of type 2 diabetes in the liver and improve glucose control.

Researchers analyzed coexpression networks and genetic data to identify a disease signature for type 2 diabetes in liver tissue. They then screened 3800 drug signatures to find compounds that could reverse this signature. Sulforaphane's effects on glucose production were tested in hepatic cells and diabetic animals. Finally, obese patients with dysregulated type 2 diabetes were given concentrated broccoli sprout extract (containing sulforaphane) to assess its impact on fasting blood glucose and HbA1c.

Sulforaphane suppressed glucose production in hepatic cells by activating NRF2 and decreasing gluconeogenesis enzyme expression. It reversed the disease signature in diabetic animal livers and reduced exaggerated glucose production and glucose intolerance to a similar extent as metformin. In obese patients with type 2 diabetes, sulforaphane, delivered as concentrated broccoli sprout extract, reduced fasting blood glucose and glycated hemoglobin (HbA1c).

Gene expression profiling can identify clinically relevant treatment options. Sulforaphane reduces hepatic glucose production and improves glucose control in patients with type 2 diabetes, suggesting it may be a useful treatment.

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


Sulforaphane Delays Fibroblast Senescence by Curbing Cellular Glucose Uptake, Increased Glycolysis, and Oxidative Damage

Sulforaphane delays cell aging by reducing sugar uptake and metabolism, which lessens cellular damage.

How does sulforaphane (SFN) delay fibroblast senescence, and what is the connection between Nrf2 activation, glucose metabolism, and oxidative damage in this process?

Hypothesis: Sulforaphane (SFN) delays fibroblast senescence by activating Nrf2, which in turn curbs cellular glucose uptake and glycolysis, thereby reducing oxidative damage.

The study investigated the effects of sulforaphane (SFN) on senescence in human MRC-5 and BJ fibroblasts. Researchers observed changes in glucose metabolism, hexokinase-2 expression, 6-phosphofructo-2-kinase, glucose-6-phosphate dehydrogenase, thioredoxin-interacting protein expression, and clearance of transglutaminase cross-linked proteins.

SFN activated Nrf2 and delayed senescence in human MRC-5 and BJ fibroblasts. Senescence was associated with increased glucose metabolism through glycolysis, leading to mitochondrial dysfunction and oxidative damage. SFN delayed senescence by decreasing glucose metabolism, exhibiting a caloric restriction mimetic-like activity, and reducing oxidative damage to cell protein and DNA. This was linked to increased thioredoxin-interacting protein, decreased hexokinase-2 and 6-phosphofructo-2-kinase, and increased glucose-6-phosphate dehydrogenase. SFN also enhanced the clearance of transglutaminase cross-linked proteins, which typically increase in senescence.

Sulforaphane delays fibroblast senescence by curbing cellular glucose uptake and glycolysis, mimicking caloric restriction, and reducing oxidative damage. This mechanism involves the modulation of key enzymes and proteins involved in glucose metabolism and protein clearance.


Antioxidant and anti-inflammatory effects of curcumin/turmeric supplementation in adults: a meta-analysis of randomized controlled trials

Turmeric/curcumin supplementation can reduce inflammation and improve antioxidant status in adults.

Does turmeric/curcumin supplementation impact inflammatory and oxidative balance in adults?

Hypothesis: Turmeric and its bioactive compound, curcumin, may affect inflammatory and oxidative balance in the body.

This systematic review and meta-analysis searched major databases (PubMed, Scopus, Web of Science, Cochrane Library, Google Scholar) up to October 2022 for randomized controlled trials (RCTs). The main outcomes included inflammatory markers (CRP, TNF-α, IL-6, IL-1β) and oxidative stress markers (TAC, MDA, SOD activity). Weighted mean differences (WMDs) were reported, with p-values < 0.05 considered significant. Sixty-six RCTs were included in the final analysis.

Turmeric/curcumin supplementation significantly reduced CRP (WMD: -0.58 mg/l), TNF-α (WMD: -3.48 pg/ml), and IL-6 (WMD: -1.31 pg/ml). No significant change was found for IL-1β (WMD: -0.46 pg/ml). Supplementation also significantly enhanced TAC (WMD = 0.21 mmol/l), reduced MDA levels (WMD = -0.33 µmol/l), and increased SOD activity (WMD = 20.51 u/l).

Turmeric/curcumin supplementation significantly reduces several inflammatory markers and improves antioxidant activity.


Profiling Inflammatory Biomarkers following Curcumin Supplementation: An Umbrella Meta-Analysis of Randomized Clinical Trials

Curcumin supplementation significantly reduces key inflammatory biomarkers like CRP, IL-6, and TNF-.

favorable-cue: "significantly reduces key inflammatory"

What is the overall effect of curcumin supplementation on inflammatory biomarkers?

Hypothesis: Curcumin supplementation will reduce inflammatory biomarkers, despite inconsistencies in previous meta-analyses.

This umbrella meta-analysis systematically searched PubMed, Scopus, Embase, Web of Science, and Google Scholar until March 20, 2022. It included meta-analysis studies on curcumin's effects on inflammatory biomarkers with corresponding effect sizes and confidence intervals. A random-effects model was used, and the GRADE system evaluated evidence certainty.

A meta-analysis of ten studies with 5,870 participants showed significant decreases in C-reactive protein (CRP) (ES = -0.74), interleukin 6 (IL-6) (ES = -1.07), and tumour necrosis factor (TNF-) levels (ES = -1.92) after curcumin supplementation. Greater effects on CRP and TNF- were observed in trials with a mean age >45 years and a sample size >300 participants.

Curcumin is a promising agent for reducing inflammation and may serve as an adjunctive therapeutic approach for diseases linked to elevated inflammatory biomarkers.

The abstract does not explicitly state limitations of the umbrella meta-analysis itself, beyond acknowledging previous inconsistencies in findings.


Effects of Quercetin on Blood Pressure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Quercetin supplementation, especially at doses of 500 mg/day or more, may help reduce both systolic and diastolic blood pressure.

Does quercetin supplementation affect blood pressure?

Hypothesis: The evidence regarding quercetin's effects on blood pressure has been inconclusive, so this meta-analysis aims to assess its impact.

A systematic review and meta-analysis of placebo-controlled randomized controlled trials were conducted. Databases including PUBMED, Cochrane Library, Scopus, and EMBASE were searched up to January 31, 2015. Meta-analysis used either fixed-effects or random-effect models, with effect size expressed as weighted mean difference (WMD) and 95% CI.

The meta-analysis included 7 trials with 9 treatment arms and 587 patients. Quercetin supplementation significantly reduced systolic BP (WMD: -3.04 mm Hg) and diastolic BP (WMD: -2.63 mm Hg). For doses ">="500 mg/day, significant reductions were observed in systolic BP (WMD: -4.45 mm Hg) and diastolic BP (WMD: -2.98 mm Hg). Doses "<"500 mg/day did not show a significant effect on either systolic BP (WMD: -1.59 mm Hg) or diastolic BP (WMD: -0.24 mm Hg), though indirect comparison tests between doses were not significant.

Quercetin supplementation has a statistically significant effect in reducing blood pressure, with this effect possibly limited to or greater with dosages of ">"500 mg/day.

The abstract does not explicitly state limitations of the study, but it does call for further studies to investigate clinical relevance and potential application as an add-on therapy.


Effect of quercetin supplementation on plasma lipid profiles, blood pressure, and glucose levels: a meta-analysis

Quercetin supplementation can lower blood pressure and may improve some lipid markers with longer-term use.

Does quercetin supplementation affect plasma lipid profiles, blood pressure, and glucose levels in humans?

Hypothesis: The study aimed to summarize evidence regarding the effects of quercetin supplementation on plasma lipid profiles, blood pressure, and glucose levels in humans.

A meta-analysis of randomized controlled trials was conducted. MEDLINE, Embase, and Scopus databases were searched from inception to July 2018. A random-effects model was used for data analysis, expressing continuous variables as weighted mean differences (WMDs) and 95%CIs. Subgroup and sensitivity analyses, as well as publication bias analyses, were also performed.

Seventeen trials with a total of 896 participants were included. Quercetin significantly lowered systolic blood pressure by -3.09 mmHg and diastolic blood pressure by -2.86 mmHg. No significant changes were observed in overall lipid profiles or glucose concentrations. However, subgroup analyses showed significant changes in high-density lipoprotein cholesterol and triglycerides in trials with a parallel design where participants consumed quercetin for 8 weeks or more.

Quercetin intake significantly decreased blood pressure in humans. Additionally, high-density lipoprotein cholesterol and triglycerides levels were significantly changed in participants who consumed quercetin for 8 weeks or more in trials with a parallel design.

The abstract does not explicitly state limitations of the meta-analysis itself, but notes that previous clinical trials reported conflicting results.


Does green tea catechin enhance weight-loss effect of exercise training? a meta-analysis of randomized trials

Adding green tea to exercise training provides only a small additional benefit for weight and fat reduction, with no extra benefit for lipid profiles.

Does green tea ingestion combined with exercise training enhance weight loss and improve lipid profiles in overweight and obese individuals compared to exercise training alone?

Hypothesis: The study aims to explore if green tea ingestion coupled with exercise training has an effect on body composition and lipid profile in overweight and obese individuals.

This systematic review and meta-analysis searched PubMed, Web of Science, and Scopus for randomized-controlled trials. Included studies compared the effect of green tea plus exercise training (EX+GT) versus exercise training alone (EX+P) in overweight or obese participants. Ten randomized trials met the inclusion criteria out of 1,015 retrieved studies.

EX+GT showed a small and consistent effect on weight (SMD = -0.30), BMI (SMD = -0.33), and fat reduction (SMD = -0.29) compared to EX+P. However, EX+GT had no greater effect on improving lipid profiles, including triglyceride (SMD = -0.92), LDL (SMD = -1.44), HDL (SMD = 0.56), and total cholesterol (SMD = -0.54).

Green tea may offer a minimal additive benefit to exercise-induced weight loss. However, it does not appear to provide additional benefits for lipid profile improvement when combined with exercise training.

The abstract does not explicitly state limitations of the meta-analysis itself, but notes that further investigations are warranted regarding green tea's effect on lipid profiles.


Effect of green tea consumption on body weight and body composition; systematic review and meta-analysis

Green tea and its extracts do not significantly impact body weight in overweight or obese adults, and their minor effect on body fat percentage is not clinically meaningful.

Does green tea consumption or its extracts (caffeine and catechins) affect body weight and body composition in overweight or obese adults?

Hypothesis: Caffeine and catechins in green tea may have a thermogenic effect that promotes weight and body fat loss.

A systematic review and meta-analysis of randomized controlled trials (RCTs) published between 2000 and 2013 was conducted. Studies included were parallel-group, randomized, double-blind, with a minimum 12-week follow-up, in healthy individuals aged 18 or older with a BMI of 25-40 kg/m2. Data was analyzed using the random effects model with a 95% confidence interval, and statistical significance was set at p < 0.05. Homogeneity was assessed using the I2 index.

Out of 154 retrieved studies, five were included in the quantitative analysis. No statistically significant mean difference was found for weight loss in Asian individuals (-0.81 kg), Caucasians (-0.73 kg), or the sample as a whole (-0.78 kg). Similarly, no statistically significant decrease was observed in BMI for Asian individuals (-0.65), Caucasians (-0.21), or the overall sample (-0.31 kg), nor for waist circumference (0.08 cm) or hip circumference. A small, statistically significant decrease in fat mass percentage (FM%) was found for the overall sample (-0.76), but not for Asian individuals (-0.76) or Caucasians (-0.76) as subgroups.

Green tea or its extracts do not have a statistically significant effect on the weight of overweight or obese adults. While a small, statistically significant decrease in the percentage of fat mass was observed, this effect is not considered clinically relevant.

The statistically significant effect on fat mass percentage was not clinically relevant. The meta-analysis included only five studies in its quantitative analysis.


Effects of Astaxanthin Supplementation on Oxidative Stress

Astaxanthin may have some antioxidant effects in humans, particularly at higher doses and shorter durations, but the overall evidence is unclear.

What is the antioxidant activity of astaxanthin in humans?

Hypothesis: The study implicitly hypothesizes that astaxanthin supplementation has an antioxidant effect in humans.

A systematic review and meta-analysis was conducted using six databases, covering studies from 1948 to 2015. Nine randomized controlled trials were included in the systematic review.

Meta-analysis showed a borderline significant antioxidant effect of astaxanthin between intervention and control groups, specifically a malondialdehyde-lowering effect for lipid peroxidation. When compared to baseline in intervention groups, astaxanthin significantly decreased plasma malondialdehyde (SMD -1.32 μmol/L) and isoprostane (SMD -3.10 ng/mL), and increased superoxide dismutase (SMD 1.57 U/mL) and total antioxidant capacity (SMD 0.77 mmol). High doses (≥20 mg/day) of astaxanthin showed significant antioxidant effects, while low doses (<20 mg/day) did not. An antioxidant effect was observed after a 3-week intervention, but not after 12-week or 3-month interventions.

The antioxidant effect of astaxanthin on humans is unclear.

The data included in the meta-analysis were insufficient. The antioxidant effect was not observed after longer intervention durations (12-week or 3-month).


Astaxanthin supplementation impact on insulin resistance, lipid profile, blood pressure, and oxidative stress: a triple-blind randomized clinical trial

Astaxanthin supplementation may improve insulin resistance, lipid profiles, and oxidative stress in infertile women with PCOS.

What is the effect of astaxanthin (ASX) supplementation on lipid profile, insulin resistance (IR), blood pressure (BP), and oxidative stress (OS) levels in infertile women with polycystic ovarian syndrome (PCOS)?

Hypothesis: Astaxanthin (ASX) supplementation may have therapeutic benefits for polycystic ovarian syndrome (PCOS) patients, potentially improving lipid profile, insulin resistance, blood pressure, and oxidative stress.

This was a triple-blind randomized clinical trial involving 58 infertile women with PCOS. Participants were randomly assigned to receive either a placebo or ASX (2 × 6 mg/day) for 8 weeks. Blood serum samples were collected before and after the intervention to evaluate fasting insulin (FI), fasting blood glucose (FBS), oxidative stress markers (malondialdehyde [MDA], superoxide dismutase [SOD], and total antioxidant capacity [TAC]), and lipid profiles. Insulin resistance indices were calculated, and blood pressure was assessed at the start and end of the study.

After 8 weeks, ASX consumption led to significant reductions in fasting blood sugar, HOMA-IR, FI, MDA, low-density lipoprotein-cholesterol, and TC/HDL-C. Conversely, ASX significantly increased TAC, HDL-C, and QUICKI. After adjusting for baseline values of age, BMI, and biochemical parameters, QUICKI and FI showed non-significant values, while other findings remained unchanged.

Astaxanthin appears to be an effective and safe supplement that improves insulin metabolism, lipid profile parameters, and oxidative stress in infertile PCOS patients.


Ergothioneine promotes longevity and healthy aging in male mice

Daily ergothioneine supplementation extended lifespan and improved multiple markers of healthy aging in male mice.

Can ergothioneine (ERGO) supplementation promote longevity and prevent age-related impairments like frailty and cognitive decline in male mice?

Hypothesis: The researchers hypothesized that daily oral supplementation of ERGO would extend lifespan and mitigate age-related impairments in male mice.

Male mice were given daily oral supplementation of ERGO (4-5 mg/kg/day) dissolved in drinking water from 7 weeks of age until the end of their lives. Lifespan, frailty, and cognitive impairment were assessed. Additionally, the effects of ERGO on the lifespan and non-frailty span of Caenorhabditis elegans were investigated. Plasma biomarkers, hippocampal neurogenesis, TDP43 protein aggregation, and microglial phenotype were also examined.

ERGO supplementation remarkably extended the lifespan of male mice and increased the life and non-frailty spans of C. elegans. At 88 weeks of age, the ERGO group showed significantly lower age-related declines in weight, fat mass, and movement velocities compared to controls. ERGO suppressed age-related increases in plasma biomarkers such as chemokine ligand 9, creatinine, symmetric dimethylarginine, urea, asymmetric dimethylarginine, quinolinic acid, and kynurenine. ERGO also rescued age-related impairments in learning and memory, which was associated with suppressed decline in hippocampal neurogenesis, reduced TDP43 protein aggregation, and promotion of microglial M2 phenotype.

Ingestion of ERGO may promote longevity and healthy aging in male mice, potentially through multiple biological mechanisms including improved physical parameters, reduced inflammatory and metabolic biomarkers, enhanced cognitive function, and beneficial effects on brain health.

The study was conducted in male mice and Caenorhabditis elegans, so the findings may not directly translate to humans. The specific mechanisms underlying all observed effects require further elucidation.


Ergothioneine: an underrecognised dietary micronutrient required for healthy ageing?

Ergothioneine, an antioxidant found in certain foods, is linked to better health outcomes in older adults and may be an essential nutrient for healthy aging.

Should ergothioneine be considered a conditionally essential micronutrient for healthy aging?

Hypothesis: The authors hypothesize that dietary ergothioneine plays critical roles in healthy aging and the prevention of cardiometabolic disease, suggesting it may be a conditionally essential micronutrient.

This is a review article that synthesizes existing evidence regarding ergothioneine's physiological functions, its role as a cellular antioxidant and cytoprotectant, and its associations with health outcomes in humans and animals.

Ergothioneine is acquired from the diet via the SLC22A4 transporter, which also reabsorbs it in the kidney. It acts as an antioxidant, chelates metals, and may regulate Nrf2 activity. Genetic knockout of SLC22A4 increases susceptibility to oxidative stress. In humans, blood levels decline after age 60, and lower levels are linked to faster cognitive decline. High plasma ergothioneine is associated with reduced cardiovascular and overall mortality risks.

The evidence reviewed suggests critical roles for dietary ergothioneine in healthy aging and preventing cardiometabolic disease, supporting the consideration of ergothioneine as a conditionally essential micronutrient.

The abstract does not explicitly state limitations of the reviewed studies or the review itself, but it does mention 'outstanding research questions in the field'.


Olive leaf extract effect on cardiometabolic profile among adults with prehypertension and hypertension: a meta-analysis

Olive leaf extract may help reduce systolic blood pressure, LDL, and inflammatory markers, but more research is needed to confirm its overall cardiometabolic benefits.

What is the effectiveness of olive leaf extract on cardiometabolic profiles among adults with prehypertension and hypertension?

Hypothesis: The study hypothesized that olive leaf extract would improve cardiometabolic profiles in prehypertensive and hypertensive individuals.

This systematic review and meta-analysis included five randomized clinical trials with 325 patients aged 18-80 years. Data from Cochrane, Medline, Embase, and trial registries were analyzed using random effects models to estimate mean differences and 95% confidence intervals for continuous outcomes. Primary outcomes were changes in systolic and diastolic blood pressure, while secondary outcomes included lipid profile, glucose metabolism, inflammatory markers, and kidney/liver functions.

A daily dose of 500 mg of olive leaf extract significantly reduced systolic BP by -5.78 mmHg over at least 8 weeks compared to placebo, but had no significant effect on diastolic BP. A 1,000 mg daily dose of olive leaf extract versus captopril reduced LDL by -6.00 mg/dl. The 500 mg daily dose also reduced inflammatory markers IL-6 by -6.83 ng/L, IL-8 by -8.24 ng/L, and TNF-alpha by -7.40 ng/L compared to placebo. No significant changes in systolic or diastolic BP were found for 1,000 mg/day of a combined formulation or 1,000 mg/day of olive leaf extract alone versus placebo.

Olive leaf extract may reduce systolic blood pressure, LDL cholesterol, and inflammatory biomarkers. However, the limited number of participants in the included trials prevents a robust conclusion regarding its overall effects on cardiometabolic profiles.

The main limitation is the small number of participants across the included trials, which may affect the robustness of the conclusions.


Clustering according to urolithin metabotype explains variability in cardiovascular risk biomarkers in individuals consuming pomegranate: a randomized clinical trial

Pomegranate extract significantly improved several cardiovascular risk biomarkers, but only in individuals with the UM-B urolithin metabotype.

Do different urolithin metabotypes (UM-A, UM-B, UM-0) influence the effects of pomegranate extract (PE) consumption on cardiovascular risk biomarkers in healthy overweight-obese individuals?

Hypothesis: The study hypothesized that interindividual variability in ellagitannin metabolism, specifically urolithin metabotypes, might explain the controversial lipid-lowering properties of pomegranate.

A double-blind, crossover, dose-response, randomized, placebo-controlled trial (POMEcardio) was conducted with 49 healthy overweight-obese participants (BMI > 27 kg/m). Participants consumed either one (dose-1, 160 mg phenolics/day) or four (dose-2, 640 mg phenolics/day) PE capsules or placebo daily for two 3-week test phases, separated by a 3-week washout period. Eighteen cardiovascular risk biomarkers were measured.

UM-B individuals had the highest baseline cardiovascular risk. After dose-2, UM-B subjects showed significant dose-dependent decreases in total cholesterol (-15.5%), LDL-cholesterol (-14.9%), small LDL-cholesterol (-47%), non-HDL-cholesterol (-11.3%), apolipoprotein-B (-12%), and oxidized LDL-cholesterol (-24%). These effects were partially correlated with urolithin production and increased Gordonibacter levels. Three (50%) UM-0 individuals became urolithin producers after PE consumption.

Urolithin metabotype clustering suggests a personalized effect of ellagitannin-containing foods like pomegranate extract on cardiovascular risk biomarkers, particularly in UM-B individuals. This personalized effect may explain the previously controversial benefits of pomegranate.

The abstract does not explicitly state limitations, but it does suggest that further research is needed on the specific role of urolithins and the microbiota associated with each urolithin metabotype.


Gene expression changes in colon tissues following intake of an ellagitannin-containing pomegranate extract: a randomized clinical trial

Pomegranate extract may modulate gene expression in colon tissues of colorectal cancer patients, but in vivo effects are complex and differ from in vitro observations.

Can dietary polyphenols, specifically ellagitannins from pomegranate extract, modify gene expression in colon tissues of colorectal cancer patients?

Hypothesis: Ellagitannins, ellagic acid, and their urolithin metabolites can modify gene expression in colon cells, suggesting they might have a similar effect in human colon tissues.

Thirty-five colorectal cancer patients were supplemented daily with 900 mg of an ellagitannin-containing pomegranate extract for 5-35 days. Gene expression in normal and cancerous colon tissues was evaluated before (biopsies) and after (surgical specimens) supplementation. Tissues from 10 control patients (no supplementation) were also analyzed to account for interindividual variability and the impact of the experimental protocol on gene expression.

The study found a large, gene- and tissue-specific interindividual variability and an impact of the experimental protocol on gene expression, with some genes induced (MYC, CD44, CDKN1A, CTNNB1), some repressed (CASP3), and others unaffected (KRAS). Despite these issues, pomegranate extract consumption was significantly associated with a counterbalance effect in the expression of CD44, CTNNB1, CDKN1A, EGFR, and TYMs. These effects were not linked to urolithin metabotypes or levels of urolithins and ellagic acid in colon tissues.

The intake of an ellagitannin-containing pomegranate extract modulated the impact of the experimental protocol on gene expression in a gene- and tissue-specific manner in colorectal cancer patients. However, these in vivo effects did not reproduce previously observed in vitro effects, highlighting the challenges in translating in vitro findings to in vivo human studies.

The study observed significant gene- and tissue-specific interindividual variability and an impact of the experimental protocol on gene expression, which complicated the interpretation of results. The in vivo effects did not align with prior in vitro findings, indicating the difficulty of demonstrating in vivo the in vitro results.


Effects of Grape Seed Proanthocyanidin Extract on Vascular Endothelial Function in Prehypertension: a Randomized Controlled Study

High-dose grape seed extract may help lower blood pressure and improve vascular elasticity in middle-aged Japanese adults with prehypertension, especially non-smokers.

What are the effects of grape seed proanthocyanidin extract (GSPE) on blood pressure and vascular endothelial function in middle-aged Japanese adults with prehypertension?

Hypothesis: The study hypothesized that GSPE consumption would improve blood pressure and vascular endothelial function in middle-aged Japanese adults with prehypertension.

A randomized, double-blind, placebo-controlled study was conducted on 6 men and 24 women aged 40-64 years with prehypertension. Participants were randomized to receive either 200 mg/day GSPE, 400 mg/day GSPE, or placebo for 12 weeks. Blood pressure, brachial flow-mediated dilation (FMD), and other cardiovascular parameters were measured at baseline and after 4, 8, and 12 weeks.

After 12 weeks, the high-dose GSPE group (400 mg/day) showed a significant decrease in mean systolic blood pressure (SBP) by 13 mmHg. FMD did not change in any group. In a post-hoc analysis of non-smoking participants, the high-dose group also showed significant improvements in mean SBP, diastolic blood pressure (DBP), stiffness parameter β, distensibility, incremental elastic modulus (Einc), and pulse wave velocity (PWV) after 12 weeks. Changes in Einc and PWV from baseline to 12 weeks were significantly greater in the high-dose group compared to the placebo group.

Consumption of high-dose GSPE (400 mg/day) may help maintain vascular elasticity and normal blood pressure in middle-aged Japanese adults with prehypertension, particularly in non-smokers.

The study's primary analysis did not find changes in FMD, and some significant findings were from an ad hoc analysis of a subgroup (non-smokers). The sample size was relatively small (30 participants).


Silybum marianum (milk thistle) and silymarin as a potential therapeutic plant in metabolic syndrome: a review

Milk thistle and its component silymarin show promise for treating metabolic syndrome due to their various health benefits.

What are the potential therapeutic effects of Silybum marianum (milk thistle) and its main component silymarin in metabolic syndrome?

Hypothesis: Silybum marianum and silymarin may exhibit beneficial effects on various components of metabolic syndrome due to their antioxidant, lipid-lowering, antihypertensive, antidiabetic, antiatherosclerotic, anti-obesity, and hepatoprotective properties.

This is a review article that summarizes existing animal and human studies on the effects of Silybum marianum in metabolic syndrome and identifies its underlying mechanisms of action.

The review found that Silybum marianum exhibits antioxidant, lipid-lowering, antihypertensive, antidiabetic, antiatherosclerotic, anti-obesity, and hepatoprotective effects, which are relevant to the management of metabolic syndrome.

Silybum marianum and its main component silymarin show potential as a therapeutic plant for metabolic syndrome due to their diverse beneficial effects.

This is a review and does not present new experimental data. The specific limitations of the individual studies reviewed are not detailed in the abstract.


Citrus polyphenol hesperidin stimulates nitric oxide production while improving endothelial function and reducing inflammatory markers in metabolic syndrome

Hesperidin improves blood vessel function and reduces inflammation in people with metabolic syndrome, potentially through its metabolite hesperetin stimulating nitric oxide production.

Does hesperetin stimulate nitric oxide production from vascular endothelium, and does oral hesperidin therapy improve endothelial function and reduce inflammatory markers in individuals with metabolic syndrome?

Hypothesis: Hesperetin, a citrus flavonoid metabolite, may stimulate nitric oxide production and improve vascular function, while oral hesperidin therapy may improve endothelial function and reduce inflammatory markers in subjects with metabolic syndrome.

Cellular mechanisms of hesperetin were studied in bovine aortic endothelial cells (BAEC) in primary culture. A randomized, placebo-controlled, double-blind, crossover trial was conducted in 24 individuals with metabolic syndrome, who received oral hesperidin (500 mg once daily for 3 weeks) or placebo. Brachial artery flow-mediated dilation and circulating inflammatory biomarkers were measured.

In BAEC, hesperetin acutely stimulated phosphorylation of Src, Akt, AMP kinase, and endothelial NO synthase, leading to NO production, which required H2O2. Hesperetin pretreatment reduced monocyte adhesion to BAEC and vascular cell adhesion molecule-1 expression induced by TNF-α. In the clinical study, hesperidin treatment increased flow-mediated dilation (10.26% vs. 7.78% with placebo) and reduced concentrations of high-sensitivity C-reactive protein, serum amyloid A protein, and soluble E-selectin.

Hesperetin has vasculoprotective actions, including stimulating NO production and reducing inflammation in endothelial cells. Oral hesperidin treatment improves endothelial dysfunction and reduces circulating inflammatory markers in individuals with metabolic syndrome.

The clinical trial was exploratory with a small sample size (n=24) and a relatively short intervention period (3 weeks).


Flavonoid apigenin is an inhibitor of the NAD+ ase CD38: implications for cellular NAD+ metabolism

The flavonoid apigenin can inhibit the enzyme CD38, leading to increased NAD+ levels and improved metabolic health in obese mice.

Can CD38 be pharmacologically inhibited to increase NAD+ levels and improve metabolic health?

Hypothesis: Inhibiting CD38 will increase cellular NAD+ levels, activate sirtuins, decrease protein acetylation, and improve metabolic syndrome parameters.

The study investigated the role of CD38 in regulating protein acetylation via NAD+ levels and sirtuin activity. It characterized quercetin and apigenin as CD38 inhibitors. Cell cultures were treated with apigenin to observe changes in NAD+ levels and protein acetylation. Obese mice were administered apigenin to assess its effects on NAD+ levels, protein acetylation, and glucose and lipid homeostasis.

CD38 regulates global protein acetylation through changes in NAD+ levels and sirtuin activity. Pharmacological inhibition of CD38 by apigenin resulted in higher intracellular NAD+ levels in cell cultures. Treatment of cell cultures with apigenin decreased global acetylation, as well as the acetylation of p53 and RelA-p65. Apigenin administration to obese mice increased NAD+ levels, decreased global protein acetylation, and improved several aspects of glucose and lipid homeostasis.

CD38 is a novel pharmacological target for treating metabolic diseases through NAD+-dependent pathways, with apigenin demonstrating efficacy as a CD38 inhibitor.


Inhibition of CD38 and nicotinamide riboside ameliorate neuroinflammation by increasing NAD

Inhibiting CD38 or supplementing with nicotinamide riboside can reduce brain inflammation by increasing NAD levels.

Does CD38 directly affect neuroinflammation by regulating brain NAD levels?

Hypothesis: CD38-mediated neuroinflammation is linked to NAD consumption, and boosting NAD through CD38 inhibition and nicotinamide riboside (NR) supplementation will suppress neuroinflammation.

The study investigated the effect of CD38 deletion, CD38 inhibition with apigenin or 78c, and NAD supplementation with nicotinamide riboside (NR) on lipopolysaccharide (LPS)-induced neuroinflammation in mice. They also used cell culture experiments with primary astrocytes and microglia to assess LPS-induced inflammatory responses.

LPS injection increased CD38 expression in the hippocampus. CD38 deletion decreased LPS-induced inflammatory responses and glial activation. Pre-administration of apigenin or NR increased NAD levels and suppressed cytokine/chemokine induction, glial activation, and neurodegeneration after LPS. In cell culture, apigenin, NAD, NR, or 78c suppressed LPS-induced inflammatory responses in astrocytes and microglia. All tested compounds suppressed the NF-κB signaling pathway in microglia.

CD38-mediated neuroinflammation is linked to NAD consumption, and increasing NAD levels through CD38 inhibition or NR supplementation directly suppresses neuroinflammation in the brain.