Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration.

The Cochrane database of systematic reviews

Cochrane review: AREDS-type antioxidant supplements slow progression to late AMD in people with existing disease but do not prevent onset in healthy eyes.


Effect of Omega-3 Fatty Acids, Lutein/Zeaxanthin, or Other Nutrient Supplementation on Cognitive Function: The AREDS2 Randomized Clinical Trial.

In older AREDS2 participants with AMD, lutein/zeaxanthin (with or without omega-3s) did not improve cognitive function over 5 years—an important null result.


Senolytics decrease senescent cells in humans: Preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease.

First-in-human senolytic trial: dasatinib+quercetin cleared senescent cells in adipose tissue and skin within 11 days and lowered circulating SASP factors (IL-1α, IL-6, MMP-9/-12) in diabetic kidney disease.


Effects of intermittent senolytic therapy on bone metabolism in postmenopausal women: a phase 2 randomized controlled trial.

Phase 2 RCT: intermittent dasatinib+quercetin did not reduce bone resorption overall in postmenopausal women (CTx −4.1% vs −7.7% control); exploratory benefit was confined to the high-senescent-cell-burden subgroup.

no-difference-cue: "did not reduce" | favorable-cue: "benefit"


Effects of quercetin supplementation on lipid profile: A systematic review and meta-analysis of randomized controlled trials.

Critical reviews in food science and nutrition

Meta-analysis of RCTs found no clinically relevant lipid effects overall; only the ≥500 mg/day for ≥4 weeks subgroup showed triglyceride reduction (−24.5 mg/dL) alongside a slight total-cholesterol rise (+3.6 mg/dL).


Senolytic therapy in mild Alzheimer's disease: a phase 1 feasibility trial.

Phase 1 trial (n=5): intermittent dasatinib+quercetin was safe and feasible in early Alzheimer's disease, with exploratory biomarker signals only.


Effects of quercetin supplementation on glycemic control among patients with metabolic syndrome and related disorders: A systematic review and meta-analysis of randomized controlled trials.

Meta-analysis in metabolic-syndrome populations found no significant effect of quercetin on fasting glucose, insulin, or HOMA-IR at usual doses.

no-difference-cue: "no significant effect"


Magnesium Bisglycinate Supplementation in Healthy Adults Reporting Poor Sleep: A Randomized, Placebo-Controlled Trial.

RCT (n=155): 250 mg elemental magnesium as bisglycinate improved insomnia severity versus placebo at 4 weeks (ISI −3.9 vs −2.3, p=0.049; small effect, d=0.2), with greater response in low-dietary-magnesium participants.


The effect of magnesium supplementation on primary insomnia in elderly: A double-blind placebo-controlled clinical trial.

Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences

RCT (n=46): 500 mg magnesium/day for 8 weeks improved insomnia severity, sleep efficiency, and sleep-onset latency in elderly adults with primary insomnia, while raising serum melatonin and lowering cortisol.


Effects of topical copper tripeptide complex on CO2 laser-resurfaced skin.

Randomized split-face study (n=13): topical copper tripeptide after CO2 laser resurfacing gave no objective benefit over control for erythema, wrinkles, or skin quality, though patient-reported satisfaction was higher (p=0.04).


Liposomes as Carriers of GHK-Cu Tripeptide for Cosmetic Application.

Formulation study showing liposomal encapsulation can carry GHK-Cu into skin, addressing the peptide's recognized stratum-corneum penetration bottleneck.


Are We Ready to Measure Skin Permeation of Modern Antiaging GHK-Cu Tripeptide Encapsulated in Liposomes?

Methods study on reliably measuring skin permeation of liposome-encapsulated GHK-Cu, underscoring that delivery remains the field's open problem.


Dose-response relationship between cocoa flavanols and human endothelial function: a systematic review and meta-analysis of randomized trials.

Meta-analysis of 18 intervention arms found cocoa flavanols improved flow-mediated dilation by +1.17% (95% CI 0.76–1.57), with an optimal effect near 710 mg flavanols per day.


Cocoa Extract Supplementation and Risk of Type 2 Diabetes: The Cocoa Supplement and Multivitamin Outcomes Study (COSMOS) Randomized Clinical Trial.

In 18,381 COSMOS participants, daily cocoa extract did not reduce incident type 2 diabetes over a median 3.6 years (HR 1.04, 95% CI 0.91–1.20)—an important null result.


A randomized, double-blind, placebo-controlled trial of oral Matricaria recutita (chamomile) extract therapy for generalized anxiety disorder.

In 57 adults with mild-to-moderate generalized anxiety disorder, 8 weeks of apigenin-standardized chamomile extract reduced anxiety scores significantly more than placebo (p = 0.047)—the main human efficacy signal for apigenin, at far lower doses than capsules provide.


Absorption, distribution, metabolism and excretion of apigenin and its glycosides in healthy male adults.

Human pharmacokinetic study: free apigenin was poorly absorbed (about 0.5% of intake recovered in urine as metabolites), while chamomile-type glycoside forms were absorbed far better (up to about 34%).


A Randomized Controlled Clinical Trial in Healthy Older Adults to Determine Efficacy of Glycine and N-Acetylcysteine Supplementation on Glutathione Redox Status and Oxidative Damage.

All-in-One Longevity Formulation;Glycine Powder

In healthy older adults, glycine plus N-acetylcysteine (GlyNAC) restored glutathione redox status and reduced oxidative damage—support for the combination, not glycine alone.


Associations between Acute Exposures to PM(2.5) and Carbon Dioxide Indoors and Cognitive Function in Office Workers: A Multicountry Longitudinal Prospective Observational Study.

Environmental research letters : ERL [Web site]

In a year-long real-world multicountry office study, acute increases in indoor CO2 and PM2.5 were associated with slower response times and lower cognitive throughput.


A single-blind field intervention study of whether increased bedroom ventilation improves sleep quality.

In real bedrooms, increasing ventilation lowered CO2 and improved sleep quality; deep sleep was significantly shorter under low-ventilation conditions.


Window/door opening-mediated bedroom ventilation and its impact on sleep quality of healthy, young adults.

Opening a bedroom window or door (lowering CO2) was associated with better sleep quality and next-day freshness in healthy young adults.


Myo-inositol effects in women with PCOS: a meta-analysis of randomized controlled trials.

Meta-analysis of 9 RCTs (247 cases, 249 controls) found myo-inositol lowered fasting insulin (SMD −1.02 µU/mL, p = 0.009) and HOMA-IR (SMD −0.585, p = 0.041) versus control in PCOS.

favorable-cue: "lowered fasting insulin"


Antenatal dietary supplementation with myo-inositol for preventing gestational diabetes.

Cochrane review of 7 RCTs (1,319 pregnant women): antenatal myo-inositol may reduce gestational diabetes (RR 0.53, 95% CI 0.31–0.90) and hypertensive disorders of pregnancy (RR 0.34), but evidence certainty was low.


Anti-aging and brightening effects of a topical treatment containing vitamin C, vitamin E, and raspberry leaf cell culture extract: A split-face, randomized controlled trial.

In a split-face randomized trial, a topical vitamin C + E formulation improved clinical signs of facial aging and skin brightness versus control.


A Combination of Nicotinamide and D-Ribose (RiaGev) Is Safe and Effective to Increase NAD(+) Metabolome in Healthy Middle-Aged Adults: A Randomized, Triple-Blind, Placebo-Controlled, Cross-Over Pilot Clinical Trial.

A small placebo-controlled crossover trial found a nicotinamide-plus-D-ribose blend safely raised the blood NAD+ metabolome in healthy middle-aged adults; endpoints were biomarkers only.


Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD(+) in healthy middle-aged and older adults.

Nicotinamide riboside (1,000 mg/day for 6 weeks) raised blood NAD+ by about 60% and was well tolerated, with exploratory signals for lower blood pressure and aortic stiffness.


DMPC-Based Liposomal Vesicles for Encapsulation and Controlled Release of NMN and Matrigel in Sarcopenia Therapy.

International journal of molecular sciences

Liposomal NMN delivery has been demonstrated only in cell and animal models; human pharmacokinetic superiority over plain NMN remains unverified.


Muscle-strengthening activities are associated with lower risk and mortality in major non-communicable diseases: a systematic review and meta-analysis of cohort studies.

Across cohort studies, about 30-60 minutes per week of muscle-strengthening activity was associated with roughly 10-20% lower risk of all-cause mortality, cardiovascular disease, total cancer and diabetes.


Histidine-containing dipeptides reduce central obesity and improve glycaemic outcomes: A systematic review and meta-analysis of randomized controlled trials.

Obesity reviews : an official journal of the International Association for the Study of Obesity

Meta-analysis of 23 randomized trials found histidine-dipeptide (carnosine/anserine) supplementation reduced waist circumference by about 3.5 cm and HbA1c by 0.76% versus control.


Histidine-containing dipeptide supplementation improves delayed recall: a systematic review and meta-analysis.

Meta-analysis of 10 RCTs found carnosine/anserine supplementation improved delayed recall by about 1.5 points on the Wechsler memory scale, with no effect on global cognitive screens.

no-difference-cue: "no effect" | favorable-cue: "improved"


Effects of Anserine/Carnosine Supplementation on Mild Cognitive Impairment with APOE4.

In 54 older adults with mild cognitive impairment, 12 weeks of anserine plus carnosine improved global Clinical Dementia Rating scores, with the benefit concentrated in APOE4 carriers.

unfavorable-cue: "impairment" | favorable-cue: "improved"


Effects of Carnosine Supplementation on Cognitive Outcomes in Prediabetes and Well-Controlled Type 2 Diabetes: A Randomised Placebo-Controlled Clinical Trial.

A 2025 placebo-controlled trial extended carnosine's glucose-control research program to neurocognitive outcomes in adults with prediabetes and well-controlled type 2 diabetes.


Pycnogenol(®) French maritime pine bark extract in randomized, double-blind, placebo-controlled human clinical studies.

A manufacturer-affiliated review of 39 randomized, double-blind, placebo-controlled trials (2,009 participants) summarizes Pycnogenol's human evidence across cardiovascular, joint, cognitive and other outcomes.


Effect of pine bark extract (Pycnogenol) on symptoms of knee osteoarthritis.

In 100 patients with knee osteoarthritis, 150 mg/day for 3 months improved WOMAC symptom and pain scores and reduced analgesic use versus placebo.


A systematic review and meta-analysis of the effects of pycnogenol on plasma lipids.

Journal of cardiovascular pharmacology and therapeutics

A dedicated meta-analysis found small favorable effects of Pycnogenol on plasma LDL and HDL cholesterol.


Efficacy of L-arginine and Pycnogenol ® in the treatment of male erectile dysfunction: a systematic review and meta-analysis.

A systematic review and meta-analysis found Pycnogenol, mainly as an adjunct with L-arginine, improved erectile-function scores versus control.


The effects of grape seed extract supplementation on cardiovascular risk factors, liver enzymes and hepatic steatosis in patients with non-alcoholic fatty liver disease: a randomised, double-blind, placebo-controlled study.

BMC complementary medicine and therapies

In 50 NAFLD patients, 520 mg/day for 2 months significantly improved insulin resistance, lipids, liver enzymes, and blood pressure versus placebo.


Grape seed extract supplementation in non-alcoholic fatty liver disease.

International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition

500 mg/day of proanthocyanidins for 2 months lowered IL-6 and malondialdehyde and raised antioxidant enzymes and quality-of-life scores in 50 NAFLD patients.


Grape seed polyphenol extract and cognitive function in healthy young adults: a randomised, placebo-controlled, parallel-groups acute-on-chronic trial.

400 mg/day for 12 weeks produced no consistent cognitive benefit, acute or chronic, in 60 healthy young adults — an honest null.


Vitis Vinifera Seed Extract Versus Micronized Purified Flavonoid Fraction for Patients with Chronic Venous Disease: A Randomized Noninferiority Trial.

A head-to-head randomized trial tested grape seed extract against the standard venoactive drug MPFF in chronic venous disease.


Effects of hesperidin in orange juice on blood and pulse pressures in mildly hypertensive individuals: a randomized controlled trial (Citrus study).

In 159 mildly hypertensive adults, sustained hesperidin-enriched orange juice for 12 weeks dose-dependently reduced systolic and pulse pressure and lowered homocysteine.


The effect of hesperidin supplementation on inflammatory markers in human adults: A systematic review and meta-analysis of randomized controlled clinical trials.

Meta-analysis of 6 RCTs (n=296) found hesperidin reduced the adhesion molecule VCAM-1 by about 22.8 ng/L, with no significant overall CRP effect.

no-difference-cue: "no significant overall crp effect"


Betaine supplementation decreases plasma homocysteine in healthy adult participants: a meta-analysis.

Across 5 RCTs at 4 g/day or more, betaine lowered plasma homocysteine by a pooled 1.23 µmol/L versus placebo.


Betaine for nonalcoholic fatty liver disease: results of a randomized placebo-controlled trial.

In 55 biopsy-proven NASH patients, 20 g/day for 12 months did not improve steatosis, disease activity, or fibrosis versus placebo — a well-conducted negative trial.


Betaine Supplementation Moderately Increases Total Cholesterol Levels: A Systematic Review and Meta-Analysis.

Meta-analysis of 6 RCTs found betaine at 4 g/day or more modestly raises total cholesterol (+0.34 mmol/L pooled), with LDL, HDL, and triglycerides unchanged.


Betaine supplementation fails to improve body composition: a systematic review and meta-analysis.

Systematic review and meta-analysis found no effect of betaine on body weight, BMI, fat mass, or fat-free mass — an honest null for a popular claim.


Decoding Betaine: A Critical Analysis of Therapeutic Potential Compared with Marketing Hype-A Narrative Review.

A critical review contrasts betaine's genuine methyl-donor biochemistry with overstated supplement marketing claims.


Effect of pneumatic compression device and stocking use on symptoms and quality of life in women with lipedema: A proof-in-principle randomized trial.

Adding pneumatic compression to compression garments improved leg circumference, bioimpedance, pain, and quality of life more than garments alone in women with lipedema.


Late-night salivary cortisol for the diagnosis of Cushing syndrome: a meta-analysis.

Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists

Late-night salivary cortisol screens for Cushing syndrome with pooled 92% sensitivity and 96% specificity across 7 studies (947 patients).


Cortisol awakening response and psychosocial factors: a systematic review and meta-analysis.

Across 147 studies, the cortisol awakening response correlated positively with job and general life stress and negatively with fatigue, burnout, and exhaustion.


Reduction in fine particulate air pollution and mortality: Extended follow-up of the Harvard Six Cities study.

American journal of respiratory and critical care medicine

Each 10 µg/m³ higher long-term PM2.5 was associated with 16% higher all-cause and 28% higher cardiovascular mortality, and cities that reduced PM2.5 saw mortality fall (RR 0.73).

unfavorable-cue: "higher cardiovascular mortality" | favorable-cue: "reduced pm2.5 saw mortality"


Five Years of Accurate PM(2.5) Measurements Demonstrate the Value of Low-Cost PurpleAir Monitors in Areas Affected by Woodsmoke.

International journal of environmental research and public health

Consumer-grade low-cost optical sensors maintained accurate PM2.5 tracking over five years of field use in wildfire-smoke-affected regions.


Measuring for change: A multi-centre pre-post trial of an air quality feedback intervention to promote smoke-free homes.

Providing households with PM2.5 monitoring plus feedback led 66% of 86 homes to reduce indoor PM2.5, by a median of 4.1 µg/m³ (−19%).


Development of Low-Cost Air Quality Stations for Next Generation Monitoring Networks: Calibration and Validation of PM(2.5) and PM(10) Sensors.

Properly calibrated low-cost optical particle sensors achieved good agreement with reference instruments in field deployments.


Current Evidence of Acetyl-L-Carnitine Use in Mood Disorders-: A Systematic Review and Meta-Analysis.

Meta-analysis of 10 trials (809 participants) confirmed a significant antidepressant effect versus placebo, comparable to standard antidepressants with fewer adverse effects.


Acetyl L-carnitine (ALC) treatment in elderly patients with fatigue.

In elderly patients with fatigue, acetyl-L-carnitine reduced physical and mental fatigue versus placebo and improved MMSE scores (+3.4 vs +0.5).


Delaying the mitochondrial decay of aging with acetylcarnitine.

Annals of the New York Academy of Sciences

Mechanistic review proposing that acetylcarnitine (with or without lipoic acid) counteracts age-related mitochondrial decay; the supporting evidence is largely preclinical.


Modern approach to topical treatment of aging skin.

Review of topical antioxidants for aging skin: alpha-lipoic acid regenerates cutaneous vitamin C, vitamin E and glutathione pools and inhibits NF-κB-driven inflammatory signaling.


Systematic Review and Meta-Analysis of L-Methylfolate Augmentation in Depressive Disorders.

Adjunctive L-methylfolate modestly improved antidepressant response versus placebo (RR 1.25 for HAMD-17 response; SMD −0.38), supporting the 15 mg/day trial findings.


Astaxanthin and meclizine extend lifespan in UM-HET3 male mice; fisetin, SG1002 (hydrogen sulfide donor), dimethyl fumarate, mycophenolic acid, and 4-phenylbutyrate do not significantly affect lifespan in either sex at the doses and schedules used.

The NIA Interventions Testing Program's rigorous multi-site mouse lifespan study found fisetin did not significantly extend lifespan at the dose and schedule tested - a key non-replication of the 2018 lifespan finding.


Effect of fisetin supplementation on inflammatory factors and matrix metalloproteinase enzymes in colorectal cancer patients.

In a double-blind RCT of 37 colorectal cancer patients on chemotherapy, fisetin 100 mg/day for 7 weeks significantly lowered plasma IL-8 and hs-CRP versus placebo.


Fisetin Prolongs Therapy Window of Brain Ischemic Stroke Using Tissue Plasminogen Activator: A Double-Blind Randomized Placebo-Controlled Clinical Trial.

Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis

Adding fisetin to delayed rt-PA stroke treatment in a double-blind RCT improved neurological scores and reduced MMP-2, MMP-9 and CRP.


New agents that target senescent cells: the flavone, fisetin, and the BCL-X(L) inhibitors, A1331852 and A1155463.

The 2017 mechanistic study that identified fisetin as a senolytic, showing it selectively induces apoptosis in senescent murine and human cells.


A Nutraceutical Containing Chlorogenic Acid and Luteolin Improves Cardiometabolic Parameters in Subjects with Pre-Obesity: A 6-Month Randomized, Double-Blind, Placebo-Controlled Study.

In a 6-month double-blind RCT in pre-obesity, a chlorogenic acid + luteolin nutraceutical (150 mg/day) improved weight, HbA1c/HOMA-IR, lipids, carotid intima-media thickness and endothelial function.


Ergothioneine levels in an elderly population decrease with age and incidence of cognitive decline; a risk factor for neurodegeneration?

Biochemical and biophysical research communications

Cross-sectional analysis found blood ergothioneine declines significantly after age 60 and is lower in people with mild cognitive impairment than in age-matched controls.


Interventions for rosacea based on the phenotype approach: an updated systematic review including GRADE assessments.

A 2019 GRADE-assessed systematic review rated azelaic acid among the topicals with high-certainty evidence for papulopustular rosacea.


Association of Office and Ambulatory Blood Pressure With Mortality and Cardiovascular Outcomes.

In an 11,135-person international cohort with median 13.8-year follow-up, each 20 mmHg higher nighttime systolic pressure was associated with 23% higher all-cause mortality and 36% higher cardiovascular-event risk, independent of office readings.

unfavorable-cue: "higher all-cause mortality"


Ambulatory blood pressure monitoring, European guideline targets, and cardiovascular outcomes: an individual patient data meta-analysis.

In a 14,230-patient pooled analysis of 14 cohorts, more of the day spent within guideline 24-hour ambulatory targets was associated with roughly half the mortality (HR 0.57) and less than a third of the cardiovascular-event risk (HR 0.30).


Screening for Hypertension in Adults: US Preventive Services Task Force Reaffirmation Recommendation Statement.

The US Preventive Services Task Force reaffirmed a Grade A recommendation for hypertension screening and advises confirming the diagnosis with ambulatory or home blood-pressure measurement before starting treatment.


Prognostic significance of visit-to-visit variability, maximum systolic blood pressure, and episodic hypertension.

Visit-to-visit variability and episodic peaks in systolic pressure predicted stroke and coronary events independently of average blood pressure, establishing variability as a risk marker in its own right.


Randomized placebo-controlled study of the memory effects of pomegranate juice in middle-aged and older adults.

The American journal of clinical nutrition

In 261 adults aged 50–75, daily pomegranate juice for 12 months kept visual memory performance stable while the placebo group declined.


Effect of the mitophagy inducer urolithin A on age-related immune decline: a randomized, placebo-controlled trial.

In 50 adults, 1,000 mg/day of urolithin A for 4 weeks expanded naive-like CD8+ T cells and remodeled immune-cell metabolism, countering markers of age-related immune decline — using the purified metabolite, not pomegranate extract.


Evidence for the effectiveness of pomegranate supplementation for blood pressure management is weak: A systematic review of randomized clinical trials.

A counterpoint systematic review judged the evidence that pomegranate supplementation lowers blood pressure to be weak and low-quality.


Randomized Crossover Trial Evaluating Detoxification of Tobacco Carcinogens by Broccoli Seed and Sprout Extract in Current Smokers.

A broccoli seed and sprout extract increased detoxication of tobacco-derived carcinogens in current smokers in a randomized crossover trial.


Protective effects of sulforaphane against toxic substances and contaminants: A systematic review.

Phytomedicine : international journal of phytotherapy and phytopharmacology

A systematic review found sulforaphane consistently upregulates detoxication and antioxidant-response pathways, supporting protection against toxic substances and contaminants.


Randomized Phase II Clinical Trial of Sulforaphane in Former Smokers at High Risk for Lung Cancer.

Cancer prevention research (Philadelphia, Pa.)

A Phase II randomized trial moved sulforaphane into a cancer-prevention setting, testing it in former smokers at high risk for lung cancer.


Efficacy and tolerability of sulforaphane in the therapeutic management of cancers: a systematic review of randomized controlled trials.

A systematic review of randomized trials in oncology settings found sulforaphane generally tolerable, with supportive but not definitive efficacy signals.


Commonly Used Dose of Montmorency Tart Cherry Powder Does Not Improve Sleep or Inflammation Outcomes in Individuals with Overweight or Obesity.

At a commonly used powder dose, Montmorency tart cherry did not improve sleep or inflammation outcomes in adults with overweight or obesity — a null randomized result.


Nutritional Modulation of Sleep Latency, Duration, and Efficiency: A Randomized, Repeated-Measures, Double-Blind Deception Study.

Medicine and science in sports and exercise

A rigorously double-blinded, repeated-measures randomized study put tart cherry and other nutritional sleep aids to a stringent test of effects on sleep latency, duration, and efficiency.


L-Carnitine treatment reduces severity of physical and mental fatigue and increases cognitive functions in centenarians: a randomized and controlled clinical trial.

In 66 centenarians, 2 g/day for 6 months reduced physical and mental fatigue, increased muscle mass (+3.8 vs +0.8 kg), reduced fat mass, and improved cognitive function versus placebo.


Beneficial effects of l-carnitine supplementation for weight management in overweight and obese adults: An updated systematic review and dose-response meta-analysis of randomized controlled trials.

A dose-response meta-analysis of randomized trials found modest weight loss (about −1.1 kg) with small BMI and fat-mass reductions, with the greatest effect near 2 g/day.


Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis.

Landmark human-and-animal work showing gut microbes convert dietary L-carnitine into TMAO, which promoted atherosclerosis — the mechanistic basis of the long-term safety debate.


The Effects of L-Carnitine Supplementation on Weight Loss, Glycemic Control, and Cardiovascular Risk Factors in Patients With Type 2 Diabetes: A Systematic Review and Dose-response Meta-Analysis of Randomized Controlled Trials.

A systematic review and meta-analysis reported improved glycemic control and cardiovascular risk factors with L-carnitine supplementation in type 2 diabetes.


Association of gamma-glutamyltransferase levels with total mortality, liver-related and cardiovascular outcomes: A prospective cohort study in the UK Biobank.

In 293,667 UK Biobank participants, high-normal GGT was associated with a 3.25-fold higher rate of liver-related mortality and a 1.43-fold higher rate of cardiovascular mortality.

unfavorable-cue: "higher rate of liver-related mortality"


Serum gamma-glutamyltransferase, oxidized LDL and mortality in the elderly.

Aging clinical and experimental research

In 1,038 elderly adults followed for a median of 9 years, serum GGT independently predicted all-cause mortality, with oxidized LDL amplifying the risk.


γ-Glutamyltransferase Variability and the Risk of Mortality, Myocardial Infarction, and Stroke: A Nationwide Population-Based Cohort Study.

In a nationwide population cohort, greater visit-to-visit GGT variability independently predicted higher risks of mortality, myocardial infarction and stroke.

unfavorable-cue: "higher risks of mortality"


Antiaging efficacy of a retinaldehyde-based cream compared with glycolic acid peel sessions: A randomized controlled study.

Over 8 weeks, a retinaldehyde cream reduced crow's-feet wrinkle depth comparably to a series of glycolic-acid peels (STm −7.61%, P = 0.0007).


The efficacy and safety of multilamellar vesicle containing retinaldehyde: A double-blinded, randomized, split-face controlled study.

In a double-blind split-face trial (n = 23), a multilamellar-vesicle retinaldehyde cream produced objective improvements in wrinkle depth, elasticity and hydration versus the control side after 8 weeks.


The Clinical Efficacy and Tolerability of a Novel Retinaldehyde Serum with Firming Peptides to Improve Skin Texture and Signs of Photoaging.

A retinaldehyde-plus-peptides serum improved skin texture and signs of photoaging with good tolerability in a 2024 clinical study.


Evidence for the Efficacy of Over-the-counter Vitamin A Cosmetic Products in the Improvement of Facial Skin Aging: A Systematic Review.

The Journal of clinical and aesthetic dermatology

A systematic review of over-the-counter vitamin A cosmetics found measurable improvement in facial skin aging, with retinaldehyde among the better-evidenced OTC retinoids.


The Efficacy of Saffron in the Treatment of Mild to Moderate Depression: A Meta-analysis.

A meta-analysis of randomized trials found saffron significantly better than placebo and not significantly different from standard antidepressants for mild-to-moderate depression.


Saffron therapy for the treatment of mild/moderate age-related macular degeneration: a randomised clinical trial.

Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie

In a double-blind placebo-controlled crossover trial (n = 100), saffron 20 mg/day for 3 months improved visual acuity and multifocal ERG latency in mild-to-moderate AMD, with benefits additive to AREDS supplements.


Influence of saffron supplementation on retinal flicker sensitivity in early age-related macular degeneration.

Investigative ophthalmology & visual science

In a randomized trial (n = 25), saffron 20 mg/day for 3 months improved focal electroretinogram amplitude versus placebo in early AMD.


Long-term insulin resistance is associated with frailty, frailty progression, and cardiovascular disease.

Journal of cachexia, sarcopenia and muscle

In a prospective cohort of older adults, a chronically insulin-resistant trajectory was associated with frailty, frailty progression and cardiovascular disease.


Association between different insulin resistance surrogates and all-cause mortality in patients with coronary heart disease and hypertension: NHANES longitudinal cohort study.

In an NHANES longitudinal cohort of patients with coronary heart disease and hypertension, insulin-resistance surrogates including HOMA-IR predicted all-cause mortality.


Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease.

In 10,061 post-MI patients with hs-CRP ≥2 mg/L, canakinumab 150 mg reduced recurrent cardiovascular events (HR 0.85) but caused more fatal infections, with no difference in all-cause mortality.


Biomarkers of Vascular Inflammation for Cardiovascular Risk Prognostication: A Meta-Analysis.

A meta-analysis found that vascular-inflammation biomarkers including hs-CRP improve cardiovascular risk prognostication.


A hypotensive protocol of inspiratory muscle strength training: Systematic review and meta-analysis with trial sequential analysis.

Journal of clinical hypertension (Greenwich, Conn.)

Meta-analysis of 12 RCTs (n=386) found inspiratory muscle strength training lowered systolic blood pressure by about 7.9 mmHg and diastolic by 3.8 mmHg, with trial sequential analysis judging the blood-pressure findings conclusive.


Inspiratory muscle strength training lowers blood pressure and sympathetic activity in older adults with OSA: a randomized controlled pilot trial.

Journal of applied physiology (Bethesda, Md. : 1985)

In a randomized trial of 25 older adults with obstructive sleep apnea, inspiratory muscle strength training lowered systolic blood pressure by about 8.8 mmHg and reduced muscle sympathetic nerve activity.


Updates in inspiratory muscle training for older adults: A systematic review.

Systematic review of 13 studies finding that 4-8 weeks of inspiratory muscle training improved cardiac autonomic control, cerebrovascular responses, balance, blood pressure and endothelial function in older adults.


The Omega-3 Index and relative risk for coronary heart disease mortality: Estimation from 10 cohort studies.

Across 10 cohort studies, each 1-SD (about 2.1%) higher Omega-3 Index was associated with 15% lower fatal CHD risk, equivalent to roughly 30% lower risk at an index of about 8% versus 4%.


ω-3 Polyunsaturated Fatty Acid Biomarkers and Coronary Heart Disease: Pooling Project of 19 Cohort Studies.

Pooling 19 cohorts (45,637 participants), each 1-SD higher blood EPA/DHA biomarker level was associated with about 9-13% lower risk of fatal coronary heart disease.


The association of biomarkers of iron status with mortality in US adults.

Nutrition, metabolism, and cardiovascular diseases : NMCD

In NHANES III (n=12,258, up to 18 years of follow-up), ferritin and transferrin saturation within the normal range were not associated with all-cause, cardiovascular, or cancer mortality.

no-difference-cue: "were not associated"


A Population-Based and Clinical Cohort Validation of the Novel Consensus Definition of Metabolic Hyperferritinemia.

The Journal of clinical endocrinology and metabolism

Population and clinical cohorts validated a consensus definition of 'metabolic hyperferritinemia', linking elevated ferritin to fatty-liver and cardiometabolic-risk phenotypes.


Effects of nattokinase on blood pressure: a randomized, controlled trial.

Hypertension research : official journal of the Japanese Society of Hypertension

In 86 adults with pre-hypertension or stage-1 hypertension, nattokinase 2,000 FU/day for 8 weeks lowered systolic blood pressure by 5.6 mmHg and diastolic by 2.8 mmHg versus placebo.


Nattokinase Supplementation and Cardiovascular Risk Factors: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Meta-analysis of 6 RCTs (n=546) found nattokinase reduced systolic blood pressure by about 3.5 mmHg and diastolic by 2.3 mmHg, with mixed lipid signals at low doses.


Inulin-type fructans supplementation improves glycemic control for the prediabetes and type 2 diabetes populations: results from a GRADE-assessed systematic review and dose-response meta-analysis of 33 randomized controlled trials.

Meta-analysis of 33 RCTs (n=1,346) found inulin-type fructans lowered fasting glucose by about 0.60 mmol/L and HbA1c by 0.58% in prediabetes and type 2 diabetes subgroups.

favorable-cue: "lowered fasting glucose"


Safety and efficacy of trehalose in amyotrophic lateral sclerosis (HEALEY ALS Platform Trial): an adaptive, phase 2/3, double-blind, randomised, placebo-controlled trial.

In the HEALEY ALS platform trial - the largest human test of trehalose to date - trehalose was well tolerated but showed no evidence of efficacy.


Clinical Use of Curcumin in Depression: A Meta-Analysis.

Journal of the American Medical Directors Association

Meta-analysis of 6 RCTs found curcumin significantly reduced depressive symptoms versus placebo when used as adjunct therapy.

favorable-cue: "significantly reduced depressive"


Memory and Brain Amyloid and Tau Effects of a Bioavailable Form of Curcumin in Non-Demented Adults: A Double-Blind, Placebo-Controlled 18-Month Trial.

The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry

In 40 non-demented adults, 18 months of Theracurmin (90 mg twice daily) improved verbal memory (effect size 0.63) and reduced amyloid/tau PET signal in the amygdala and hypothalamus versus placebo.


A phase I study investigating the safety and pharmacokinetics of highly bioavailable curcumin (Theracurmin) in cancer patients.

Human pharmacokinetic study showing the highly bioavailable Theracurmin formulation achieves markedly higher plasma curcumin levels than standard curcumin powder.


Liver Injury Associated with Turmeric-A Growing Problem: Ten Cases from the Drug-Induced Liver Injury Network [DILIN].

Drug-Induced Liver Injury Network case series of 10 turmeric-associated liver injuries, most involving high-bioavailability products combined with piperine.


Cystatin C estimated glomerular filtration rate and all-cause and cardiovascular disease mortality risk in the general population: AusDiab study.

In a general-population cohort, cystatin C-based eGFR independently predicted all-cause and cardiovascular mortality.


Cystatin C for predicting all-cause mortality and rehospitalization in patients with heart failure: a meta-analysis.

Meta-analysis: elevated cystatin C was associated with worse all-cause mortality and rehospitalization outcomes in patients with heart failure.


A Greater Flavonoid Intake Is Associated with Lower Total and Cause-Specific Mortality: A Meta-Analysis of Cohort Studies.

Across 16 cohorts and 462,194 adults, higher flavonoid intake was associated with 13% lower all-cause and 15% lower cardiovascular mortality; the cancer-mortality association was not significant.

favorable-cue: "lower cardiovascular mortality"


High diversity of dietary flavonoid intake is associated with a lower risk of all-cause mortality and major chronic diseases.

In 124,805 UK Biobank participants, the widest flavonoid diversity was associated with 6–20% lower all-cause mortality and lower incidence of several major chronic diseases.

favorable-cue: "lower all-cause mortality"


The Effect of Antioxidant Polyphenol Supplementation on Cardiometabolic Risk Factors: A Systematic Review and Meta-Analysis.

Across 281 RCTs (17,126 participants), polyphenol supplements modestly improved cardiometabolic markers—catechins lowered systolic blood pressure ~1.6 mmHg, anthocyanins improved lipids, curcumin improved glucose handling.


Polyphenol Health Effects on Cardiovascular and Neurodegenerative Disorders: A Review and Meta-Analysis.

International journal of molecular sciences

Some polyphenols improved specific cardiovascular-risk and cognitive markers, but the authors judged the data too inconsistent for definitive prevention recommendations.


The Effects of an Oral Taurine Dose and Supplementation Period on Endurance Exercise Performance in Humans: A Meta-Analysis.

Meta-analysis of 10 studies: oral taurine improved endurance exercise performance with a small-to-moderate effect.


Profiling inflammatory and oxidative stress biomarkers following taurine supplementation: a systematic review and dose-response meta-analysis of controlled trials.

Dose-response meta-analysis of controlled trials: taurine supplementation reduced inflammatory and oxidative-stress biomarkers.


Oral Muvalaplin for Lowering of Lipoprotein(a): A Randomized Clinical Trial.

Randomized trial: the first oral small-molecule Lp(a) inhibitor muvalaplin lowered Lp(a), showing a needle-free option is feasible.


Removal of metals and assimilable organic carbon by activated carbon and reverse osmosis point-of-use water filtration systems.

Water Purification (Reverse Osmosis & Ultrafiltration)

In controlled bench testing, point-of-use RO removed >95% of manganese and uranium and >98% of calcium, magnesium, iron, and copper, while activated carbon was generally ineffective for metals.


Removal of perfluoroalkyl and polyfluoroalkyl substances from tap water by means of point-of-use treatment: A review.

Review: RO, ion exchange, and granular activated carbon are the leading point-of-use PFAS-removal technologies, though real-world performance and maintenance are understudied.


Reduced risk estimations after remediation of lead (Pb) in drinking water at two US school districts.

Modeling across 664 remediated schools estimated that filtration and lead-plumbing fixes materially cut the share of students predicted to exceed 5 µg/dL blood lead (from ~11.2% on average).


Blood Lead Levels Among Children Aged <6 Years - Flint, Michigan, 2013-2016.

MMWR. Morbidity and mortality weekly report

CDC surveillance found the probability of elevated blood lead in Flint children rose after the 2014 water-source switch—a case study in why drinking-water contaminant control matters.


Action spectrum for melatonin regulation in humans: evidence for a novel circadian photoreceptor.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Blue-Light Management & Circadian Lighting

Identified short-wavelength blue light near 460 nm as the most potent part of the visible spectrum for suppressing human melatonin — the mechanistic basis for evening blue-light blocking.


Associations of regular glucosamine use with all-cause and cause-specific mortality: a large prospective cohort study.

Regular glucosamine use was associated with 15% lower all-cause mortality (HR 0.85) and 18% lower cardiovascular mortality among 495,077 UK Biobank participants — observational, so it cannot prove cause.


Pterostilbene on metabolic parameters: a randomized, double-blind, and placebo-controlled trial.

Evidence-based complementary and alternative medicine : eCAM

High-dose pterostilbene lowered blood pressure by 7.8/7.3 mmHg but raised LDL cholesterol by 17.1 mg/dL on monotherapy — a safety signal for this formula's resveratrol analog.

unfavorable-cue: "raised ldl" | favorable-cue: "lowered blood pressure"


Effects of Magnesium Supplementation on Blood Pressure: A Meta-Analysis of Randomized Double-Blind Placebo-Controlled Trials.

Across 34 double-blind RCTs, magnesium at about 368 mg/day lowered systolic blood pressure by 2.0 mmHg and diastolic by 1.8 mmHg.


A meta-analysis of low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B as markers of cardiovascular risk.

Circulation. Cardiovascular quality and outcomes

In a meta-analysis of 233,455 people, apoB was the strongest lipid risk marker (relative-risk ratio 1.43 vs 1.34 for non-HDL-C and 1.25 for LDL-C), beating LDL-C by 12%.


Role of apolipoprotein B in the clinical management of cardiovascular risk in adults: An Expert Clinical Consensus from the National Lipid Association.

National Lipid Association expert consensus recommends apoB measurement to refine cardiovascular risk, especially in people with diabetes, obesity, high triglycerides or discordant LDL-C.


Exercise Interventions for the Prevention and Treatment of Sarcopenia. A Systematic Umbrella Review.

The journal of nutrition, health & aging

Umbrella review of exercise trials identifies resistance-based training, including blood flow restriction, as an effective countermeasure against age-related muscle loss.


Effect of resveratrol on C-reactive protein: An updated meta-analysis of randomized controlled trials.

Across 35 RCTs, resveratrol lowered hs-CRP by 0.40 mg/L and CRP by 0.31 mg/L, with the strongest effects at 500 mg/day or more for at least 10 weeks.


Long-term effects of resveratrol on cognition, cerebrovascular function and cardio-metabolic markers in postmenopausal women: A 24-month randomised, double-blind, placebo-controlled, crossover study.

Clinical nutrition (Edinburgh, Scotland)

Over 24 months, 75 mg twice-daily resveratrol improved overall cognitive performance by 33% versus placebo and enhanced cerebral blood flow and insulin sensitivity in postmenopausal women — a single-cohort result awaiting replication.


Glucose-lowering effect of berberine on type 2 diabetes: A systematic review and meta-analysis.

Across 37 RCTs (n=3,048) in type 2 diabetes, berberine lowered fasting glucose by about 0.82 mmol/L and HbA1c by about 0.63% without increasing hypoglycemia — though the underlying trials were mostly small and of variable quality.


Efficacy of berberine in patients with type 2 diabetes mellitus.

In a pilot RCT, berberine 0.5 g three times daily lowered HbA1c from 9.5% to 7.5% over 3 months — comparable to metformin in the parallel arm — with transient gastrointestinal effects in about a third of patients.


Vitamin D(3) and marine ω-3 fatty acids supplementation and leukocyte telomere length: 4-year findings from the VITamin D and OmegA-3 TriaL (VITAL) randomized controlled trial.

The American journal of clinical nutrition

In a VITAL randomized substudy of about 1,000 adults, vitamin D3 2,000 IU/day significantly slowed leukocyte telomere attrition over 4 years (roughly 140 bp preserved vs placebo) — the first large RCT signal on a biological-aging marker, from an ancillary analysis that needs replication.


Oral supplementation with liposomal glutathione elevates body stores of glutathione and markers of immune function.

A 1-month open-label pilot (n=12) found liposomal glutathione raised whole-blood GSH about 40% and PBMC GSH about 100%, cut plasma 8-isoprostane about 35%, and raised NK-cell cytotoxicity up to about 400% — small, uncontrolled and industry-funded.


Glutathione as an oral whitening agent: a randomized, double-blind, placebo-controlled study.

In a 4-week RCT (n=60), oral glutathione 500 mg/day lowered skin melanin index at all six measured sites but beat placebo significantly at only two — a modest, short-term effect with no follow-up.


Glutathione as a skin whitening agent: Facts, myths, evidence and controversies.

Indian journal of dermatology, venereology and leprology

A critical review found only two small human RCTs of oral glutathione for skin lightening, rating the evidence weak and long-term safety — especially of intravenous use — unestablished.


Randomized trial of a portable HEPA air cleaner intervention to reduce asthma morbidity among Latino children in an agricultural community.

Environmental health : a global access science source

In a 12-month RCT (n=75 children with poorly controlled asthma), bedroom and living-room HEPA cleaners missed the primary asthma-control endpoint but were associated with roughly 55–57% lower risk of poorly controlled episodes in secondary analyses — an honestly mixed result.


Individual- and Household-Level Interventions to Reduce Air Pollution Exposures and Health Risks: a Review of the Recent Literature.

A systematic review found portable air cleaners consistently reduce indoor particle exposure with some subclinical cardiovascular benefits, while health-outcome trials of gas-phase (VOC) interventions remain sparse.


Novel glucose-sensing technology and hypoglycaemia in type 1 diabetes: a multicentre, non-masked, randomised controlled trial.

In this 241-patient RCT, flash glucose monitoring cut time spent in hypoglycemia by 38% versus fingerstick self-monitoring in adults with well-controlled type 1 diabetes.


The efficacy of using continuous glucose monitoring as a behaviour change tool in populations with and without diabetes: a systematic review and meta-analysis of randomised controlled trials.

The international journal of behavioral nutrition and physical activity

Across 25 RCTs (n=2,996), CGM as a behavior-change tool produced modest glycemic improvements (HbA1c −0.28%, time in range +7.4%), driven mostly by participants with diabetes, with no significant effect on weight or BMI.

no-difference-cue: "no significant effect" | favorable-cue: "improvements"


The efficacy of a daily self-weighing weight loss intervention using smart scales and e-mail.

In this 91-person RCT, daily smart-scale weighing with email feedback produced −6.55% body weight at 6 months versus −0.35% in controls (42.6% vs 6.8% achieved ≥5% loss).


Is self-weighing an effective tool for weight loss: a systematic literature review and meta-analysis.

Self-weighing improved weight loss when embedded in multi-component programs (−1.7 to −3.4 kg) but showed no effect as stand-alone advice (−0.5 kg, ns) in the one trial testing it.


Validation of the Body Scan(®), a new device to detect small fiber neuropathy by assessment of the sudomotor function: agreement with the Sudoscan(®).

The Body Scan's foot electrochemical skin conductance detected small-fiber neuropathy with 0.91 sensitivity and 0.97–0.99 specificity versus the hospital-grade Sudoscan reference (n=147)—a rare device-specific clinical validation.


Body composition using bioelectrical impedance: Development and validation of a predictive equation for fat-free mass in a middle-income country.

DXA-referenced BIA equations explained >80% of fat-free-mass variance at group level, illustrating why consumer impedance readings suit trends but remain error-prone for individuals.


Evaluation of a Handheld Gluten Detection Device.

Across 13 spiked food matrices, a handheld gluten sensor detected gluten reliably at ≥20 ppm (5.9% failure) with 3.6% false positives, but was unreliable at 5 ppm and in pasta matrices.


Benefits From and Barriers to Portable Detection of Gluten, Based on a Randomized Pilot Trial of Patients With Celiac Disease.

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association

In this randomized pilot, celiac patients rated a portable gluten sensor an acceptable aid to gluten-free-diet adherence and quality of life, while citing cost, capsule supply, and false-result anxiety as barriers.


Accidental ingestions in children with peanut allergy.

The Journal of allergy and clinical immunology

In a prospective cohort of 252 children with peanut allergy, accidental exposures occurred at 14.3% per year, and most moderate-to-severe reactions were managed without epinephrine.


Efficacy and cost-effectiveness of nurse-led care involving education and engagement of patients and a treat-to-target urate-lowering strategy versus usual care for gout: a randomised controlled trial.

Nurse-led treat-to-target care achieved serum urate <360 µmol/L in 95% of gout patients versus 30% with usual care at 2 years (RR 3.18), and was cost-effective—evidence that monitoring-guided urate control works.


Nurse-supported self-monitoring of serum urate by gout patients using a treat-to-target approach: a feasibility study.

In this 24-week feasibility study, 32 gout patients self-measured serum urate at home with a point-of-care meter with 93% adherence and 75% reaching the urate target—direct but early evidence for home monitoring.


An analytical comparison between point-of-care uric acid testing meters.

Four commercial point-of-care urate meters showed good usability and precision against LC-MS, with meter-versus-laboratory correlations of R²≈0.76–0.81—serviceable for trending, not diagnosis.


Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial.

Over 3 years in 212 patients, placebo knees lost −0.31 mm of joint space while glucosamine sulfate knees lost only −0.06 mm (ns), with WOMAC symptoms improving on glucosamine versus slight worsening on placebo.


Glucosamine and lower mortality and cancer incidence: Selection bias in the observational studies.

D-Glucosamine;Osteo Bi-Flex (Triple Strength + Joint Shield)

A methodological critique argues the lower mortality and cancer incidence attributed to glucosamine in observational cohorts are inflated by selection and healthy-user bias—longevity claims remain unproven.


Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children.

The Cochrane database of systematic reviews

Cochrane review of 31 RCTs (8,672 participants): probiotics cut the risk of C. difficile-associated diarrhea during antibiotic use by 60% (1.5% vs 4.0%; RR 0.40, moderate certainty).


Probiotics for preventing acute upper respiratory tract infections.

Cochrane update: probiotics reduced the number of people diagnosed with at least one acute upper respiratory infection (RR 0.76) and shortened episodes by about 1.2 days.


Efficacy of Single-Strain Probiotics Versus Multi-Strain Mixtures: Systematic Review of Strain and Disease Specificity.

Systematic review of 65 RCTs (10,863 participants): multi-strain mixtures were not significantly more effective than single strains within the same indication in most cases.


Systematic review and meta-analysis: Multi-strain probiotics as adjunct therapy for Helicobacter pylori eradication and prevention of adverse events.

United European gastroenterology journal

Meta-analysis: multi-strain probiotic adjuncts improved H. pylori eradication rates and reduced antibiotic-associated side effects.


Akkermansia muciniphila supplementation in patients with overweight/obese type 2 diabetes: Efficacy depends on its baseline levels in the gut.

12-week RCT in overweight/obese type 2 diabetes (n=58): no overall between-group benefit, but significant weight, fat-mass and HbA1c reductions in participants with low baseline gut Akkermansia.


Pasteurized Akkermansia muciniphila Muc(T) for weight loss maintenance in people with overweight and obesity: a controlled randomized trial.

Randomized controlled trial: pasteurized A. muciniphila MucT supported weight-loss maintenance in people with overweight and obesity.


Pasteurized Akkermansia muciniphila HB05 (HB05P) Improves Muscle Strength and Function: A 12-Week, Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

12-week RCT: pasteurized A. muciniphila strain HB05 improved muscle strength and function versus placebo.


The effects of inulin-type fructans on cardiovascular disease risk factors: systematic review and meta-analysis of randomized controlled trials.

Meta-analysis of 55 RCTs (n=2,518): inulin-type fructans produced small LDL cholesterol (-0.14 mmol/L) and triglyceride (-0.06 mmol/L) reductions, with GRADE certainty rated low to very low.


Inulin-induced improvements on bowel habit and gut microbiota in adults with functional constipation: findings of a randomized, double-blind, placebo-controlled study.

Randomized double-blind placebo-controlled trial: 12 g/day inulin improved stool frequency and abdominal symptoms in functional constipation and modulated gut microbiota.


Dietary nitrate provides sustained blood pressure lowering in hypertensive patients: a randomized, phase 2, double-blind, placebo-controlled study.

Pivotal RCT in hypertensive patients (n=68, 4 weeks): daily nitrate-rich beetroot juice lowered clinic BP by 7.7/2.4 mmHg and 24-h ambulatory BP by 7.7/5.2 mmHg, improved endothelial function ~20%, with no tachyphylaxis.


Nitrate Derived From Beetroot Juice Lowers Blood Pressure in Patients With Arterial Hypertension: A Systematic Review and Meta-Analysis.

Meta-analysis of 7 RCTs in hypertension (n=218): beetroot-juice nitrate lowered systolic BP by 4.95 mmHg (GRADE moderate); diastolic effect not significant.


Dietary Nitrate Supplementation and Exercise Performance: An Umbrella Review of 20 Published Systematic Reviews with Meta-analyses.

Umbrella review of 20 meta-analyses (180 studies, n=2,672): nitrate improved time-to-exhaustion (SMD 0.33), muscular endurance (SMD 0.48) and peak power (SMD 0.25), best at >=6 mmol/day, though underlying review quality was often low.


Dietary Polyphenol and Methylsulfonylmethane Supplementation Improves Immune, DAMP Signaling, and Inflammatory Responses During Recovery From All-Out Running Efforts.

In healthy adults, an MSM-plus-polyphenol supplement blunted immune, damage-associated (DAMP) and inflammatory signaling during recovery from exhaustive running - a combination formula, not MSM alone.


Systematic Review and Meta-Analysis on Using Acupressure to Promote the Health of Older Adults.

Journal of applied gerontology : the official journal of the Southern Gerontological Society

Meta-analysis of trials in older adults found acupoint acupressure improved outcomes including sleep and quality of life - evidence for the targeted technique, not for spike mats specifically.


Human brain (7)Li-MRI following low-dose lithium dietary supplementation in healthy participants.

7Li-MRI showed that low-dose lithium dietary supplements measurably increase human brain lithium in healthy volunteers - direct proof that supplement doses reach the brain.


Different pharmacokinetics of lithium orotate inform why it is more potent, effective, and less toxic than lithium carbonate in a mouse model of mania.

In a mouse model, lithium orotate showed distinct pharmacokinetics with roughly 10-fold greater potency and lower toxicity than lithium carbonate - preclinical only, not confirmed in humans.


A toxicological evaluation of lithium orotate.

Regulatory toxicology and pharmacology : RTP

A formal toxicological evaluation characterized the safety profile of the lithium orotate salt itself, which remains far less studied than prescription lithium carbonate.


A Survey Exploring People's Experiences With Lithium Bought as a Supplement: Une enquête sur l'expérience des personnes avec le lithium en supplément.

Canadian journal of psychiatry. Revue canadienne de psychiatrie

A 2025 survey of people self-using over-the-counter lithium supplements found perceived mood and cognitive benefits alongside substantial knowledge gaps about dosing and safety.


Long term outcomes of hyperbaric oxygen therapy in post covid condition: longitudinal follow-up of a randomized controlled trial.

Symptomatic and quality-of-life gains from a randomized hyperbaric oxygen trial in post-COVID condition were maintained at roughly one-year follow-up.


Safety of Topical Non-steroidal Anti-Inflammatory Drugs in Osteoarthritis: Outcomes of a Systematic Review and Meta-Analysis.

Systematic safety review found topical NSAIDs cause mainly mild local skin reactions with far fewer gastrointestinal and systemic adverse events than oral NSAIDs, supporting their preferential use in older adults.


Efficacy and safety of topical capsaicin in the treatment of osteoarthritis pain: A systematic review and meta-analysis.

Meta-analysis of 8 RCTs (n=498) found topical capsaicin superior to placebo for osteoarthritis pain (SMD −0.84) but rated certainty low to very low, with application-site burning common (number-needed-to-harm 3).


Topical capsaicin for pain management: therapeutic potential and mechanisms of action of the new high-concentration capsaicin 8% patch.

Mechanism review explaining how repeated capsaicin application depletes substance P and reversibly 'defunctionalizes' TRPV1-expressing pain fibers, producing localized analgesia with minimal systemic absorption.


A comparison of transdermal over-the-counter lidocaine 3.6% menthol 1.25%, Rx lidocaine 5% and placebo for back pain and arthritis.

Double-blind RCT (n=87): an over-the-counter-strength lidocaine patch was non-inferior to the prescription 5% patch and superior to placebo for back pain and arthritis.


Comparison of the effectiveness and tolerability of lidocaine patch 5% versus celecoxib for osteoarthritis-related knee pain: post hoc analysis of a 12 week, prospective, randomized, active-controlled, open-label, parallel-group trial in adults.

Randomized active-controlled trial found the lidocaine 5% patch produced WOMAC pain improvement comparable to celecoxib 200 mg/day for knee osteoarthritis, with better tolerability.


Effect and safety profile of topical lidocaine on post-surgical neuropathic pain and quality of life: A systematic review and meta-analysis.

Meta-analysis found topical lidocaine reduces post-surgical neuropathic pain and improves quality of life.


Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis.

Landmark meta-analysis of neuropathic-pain pharmacotherapy places lidocaine plasters among second-line options for peripheral neuropathic pain, with a favorable safety profile.


Cutaneous application of menthol 10% solution as an abortive treatment of migraine without aura: a randomised, double-blind, placebo-controlled, crossed-over study.

International journal of clinical practice

Topical Menthol (Cooling Counterirritant)

Randomized triple-blind crossover trial (n=35, 118 attacks): a 10% menthol solution applied to the head and neck beat placebo on 2-hour pain-free and pain-relief endpoints.


Topical menthol increases cutaneous blood flow.

Human randomized physiology study showing topical menthol dose-dependently increases skin blood flow across the treated area, a plausible contributor to its analgesic effect.


Potentiation of warfarin anticoagulation associated with topical methyl salicylate.

Topical Methyl Salicylate + Menthol (Medicated Patch)

Case report: percutaneous absorption of topical methyl salicylate potentiated warfarin anticoagulation, a flag for users on blood thinners.


From Chemical Burn to Below Knee Amputation: Amputation Secondary to Application of Over-the-Counter Topical Analgesic With Menthol and Methyl Salicylate.

Case report: misuse of an occlusive menthol/methyl-salicylate topical caused a severe chemical burn culminating in amputation — a rare but sobering misuse risk.


Association of habitual glucosamine use with risk of cardiovascular disease: prospective study in UK Biobank.

Osteo Bi-Flex (Triple Strength + Joint Shield)

In ~466,000 UK Biobank participants, habitual glucosamine use was associated with about 15% fewer cardiovascular events and 22% lower cardiovascular death — observational, not causal.


Randomized trial of glucosamine and chondroitin supplementation on inflammation and oxidative stress biomarkers and plasma proteomics profiles in healthy humans.

In a small randomized crossover trial (n=18), glucosamine plus chondroitin lowered serum CRP by 23% versus placebo, supporting an anti-inflammatory mechanism.


Randomised, Double-Blind, Parallel, Placebo-Controlled Study of Oral Glucosamine, Methylsulfonylmethane and their Combination in Osteoarthritis.

Glucosamine + Chondroitin (+ MSM);MSM (OptiMSM)

In 118 patients, glucosamine and MSM each beat placebo, and the combination reduced pain and swelling most (pain index 1.7 to 0.36, p<0.001) over 12 weeks.


Methylsulfonylmethane: Applications and Safety of a Novel Dietary Supplement.

Review of MSM's mechanisms (sulfur donor, NF-kB inhibition, antioxidant effects) and safety: GRAS status, well tolerated up to about 6 g/day with mild GI effects.


Beauty from within: Oral administration of a sulfur-containing supplement methylsulfonylmethane improves signs of skin ageing.

International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition

In a placebo-controlled trial, oral MSM improved expert-graded signs of skin aging such as wrinkles and texture.


Modified-Release Phosphatidylcholine (LT-02) for Ulcerative Colitis: Two Double-Blind, Randomized, Placebo-Controlled Trials.

Two large phase 3 trials (466 induction, 150 maintenance patients) found modified-release phosphatidylcholine no better than placebo in ulcerative colitis; the induction trial was stopped early for futility.


Lecithin for dementia and cognitive impairment.

Cochrane review of 12 randomized trials found no clear clinical benefit of lecithin for Alzheimer's disease, Parkinsonian dementia, or subjective memory problems.


Lecithin Alleviates Memory Deficits and Muscle Attenuation in Chinese Older Adults and SAMP8 Mice.

Advanced science (Weinheim, Baden-Wurttemberg, Germany)

A nationwide cohort plus embedded RCT and mouse work linked lecithin intake to protection against combined sarcopenia and mild cognitive impairment via a PGC1a-FNDC5/irisin pathway — preliminary and unreplicated.


Choline: an essential nutrient for public health.

Reviews choline's essential roles — acetylcholine synthesis, hepatic VLDL export and methyl donation — and human deficiency consequences such as fatty liver and muscle damage.


Omega-3 long chain fatty acid "bioavailability": a review of evidence and methodological considerations.

This review considers the bioavailability of different forms of omega-3 long chain polyunsaturated fatty acids (n-3 LC-PUFA), including ethyl esters (EEs), free fatty acids (FFAs), triacylglycerols (TAGs) and phospholipids (PLs).


Steady-state bioavailability of prescription omega-3 on a low-fat diet is significantly improved with a free fatty acid formulation compared with an ethyl ester formulation: the ECLIPSE II study.

The systemic bioavailability of free fatty acid (FFA) forms of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) compared with ethyl ester (EE) forms is dependent on the presence of intestinal lipases and is highest during consumption of high-fat meals.


A Randomized, Open-Label, Single-Dose, Crossover Study of the Comparative Bioavailability of EPA and DHA in a Novel Liquid Crystalline Nanoparticle-Based Formulation of ω-3 Acid Ethyl Ester Versus Omacor® Soft Capsule among Healthy Adults.

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are well known for their capacity to lower triglyceride levels, but the clinical effectiveness is hindered by limited bioavailability and patient adherence.


Analysis of the efficacy, safety, and regulatory status of novel forms of creatine.

Studies have indicated that CM is not degraded during normal digestion and that nearly 99% of orally ingested CM is either taken up by muscle or excreted in urine.


Bioavailability, Efficacy, Safety, and Regulatory Status of Creatine and Related Compounds: A Critical Review.

In 2011, we published a paper providing an overview about the bioavailability, efficacy, and regulatory status of creatine monohydrate (CrM), as well as other "novel forms" of creatine that were being marketed at the time.


Absolute Oral Bioavailability of Creatine Monohydrate in Rats: Debunking a Myth.

Our objective was to determine the oral bioavailability of CM and the influence of dose on oral absorption.


Oral bioavailability of the antioxidant astaxanthin in humans is enhanced by incorporation of lipid based formulations.

Astaxanthin is also available as a food supplement, but, like other carotenoids, is a very lipophilic compound and has low oral bioavailability.


Nutraceutical Potential of Astaxanthin in Muscle Metabolism, Exercise Adaptation, and Obesity.

Emerging evidence highlights the importance of optimized delivery strategies to enhance AX bioavailability and mitochondrial targeting.


Characterization and quantitation of a zinc-binding ligand in human milk.

Weanling rats fed supplemental picolinic acid absorbed significantly more dietary zinc and gained significantly more weight than rats fed an unsupplemented diet.


[Zinc and chronic enteropathies].

The disease is related to the malfunctioning of intestinal absorption of zinc and can be treated by administering pharmacological doses of zinc orally.


Studies on the bioavailability of zinc in humans: intestinal interaction of tin and zinc.

We have explored the tin/zinc interaction using the change-in-plasma-zinc-concentration method with a standard dosage of 12.5 mg of zinc as zinc sulfate in 100 ml of Coca-Cola.


US Pharmacopeial Convention safety evaluation of menaquinone-7, a form of vitamin K.

Menaquinone-7 has greater bioavailability than other forms of vitamin K, which has led to increasing sales and use of menaquinone-7 supplements.


MK-7 and Its Effects on Bone Quality and Strength.

MK-7 has higher efficacy due to its higher bioavailability and longer half-life than other vitamin K homologs.


Cis and trans isomers of the vitamin menaquinone-7: which one is biologically significant?

Recently, several studies have indicated that an adequate intake of menaquinone-7 (MK-7) offers numerous health benefits.


The study of bioavailability and endogenous circadian rhythm of menaquinone-7, a form of vitamin K2, in healthy subjects.

A simple and rapid LC-APCI-MS/MS method for the determination of MK-7 in human plasma with single liquid-liquid extraction (LLE) extraction and 4·5-min analysis time has been developed and validated.


Silybin and the liver: from basic research to clinical practice.

Results indicate that the bioavailability of silybin phytosome is higher than that of silymarin and is less influenced by liver damage; silybin does not show significant interactions with other drugs and at doses < 10 g/d has no significant side effects.

no-difference-cue: "no significant side effects"


Silybin phytosome attenuates cerebral ischemia-reperfusion injury in rats by suppressing oxidative stress and reducing inflammatory response: In vivo and in silico approaches.

High-performance liquid chromatography was used to carry out bioavailability studies of SIBP.


Epigallocatechin gallate: Phytochemistry, bioavailability, utilization challenges, and strategies.

It is susceptible to lower stability, lesser bioavailability, and lower absorption rate due to various environmental, processing, formulations, and gastrointestinal conditions of the human body.


Absorption, metabolism, bioactivity, and biotransformation of epigallocatechin gallate.

However, the poor bioavailability of EGCG restricts its use.


Tea Polyphenol Epigallocatechin Gallate and the Gut-Health Axis: Unraveling Structural Characteristics, Metabolic Pathways, and Systemic Benefits.

However, the direct absorption of EGCG is limited due to its low oral bioavailability, with a substantial portion reaching the colon where it interacts extensively with gut microbiota.


Human absorption and metabolism of oleuropein and hydroxytyrosol ingested as olive (Olea europaea L.) leaf extract.

To quantify the bioavailability and metabolism of oleuropein and hydroxytyrosol when taken as OLE, nine volunteers (five males) aged 42.8 ± 7.4 years were randomized to receive either capsulated or liquid OLE as a single lower (51.1 mg oleuropein, 9.7 mg hydroxytyrosol) or higher (76.6 mg oleuropein, 14.5 mg hydroxytyrosol) dose, and then the opposite strength (but same formulation) a week later.


Oral Bioavailability and Metabolism of Hydroxytyrosol from Food Supplements.

Bioavailability studies with olive oils showed that HT is bioavailable from its free form and from conjugated forms such as oleuropein and its aglycone.


Metabolism and Bioavailability of Olive Bioactive Constituents Based on In Vitro, In Vivo and Human Studies.

The present critical review aimed to gather all scientific data of the past two decades regarding the absorption and metabolism of the foremost olive compounds, specifically of the phenylalcohols hydroxytyrosol (HTyr) and tyrosol (Tyr) and the secoiridoids oleacein (Olea), oleocanthal (Oleo) and oleuropein (Oleu).


Insights on the Use of α-Lipoic Acid for Therapeutic Purposes.

Data suggests that ALA has a short half-life and bioavailability (about 30%) triggered by its hepatic degradation, reduced solubility as well as instability in the stomach.


(R)-α-lipoic acid oral liquid formulation: pharmacokinetic parameters and therapeutic efficacy.

Indeed, phenomena such as reduced solubility, lack of gastric stability and hepatic degradation determine a bioavailability of around 30% and a short half-life of ALA.


Age and gender dependent bioavailability of R- and R,S-α-lipoic acid: a pilot study.

Despite this rationale for benefiting human health, little is known about age-associated alterations in absorption characteristics of LA, or whether the commercially available racemic mixture of LA (R,S-LA) is equally as bioavailable as the naturally occurring R-enantiomer.


A Randomized, Double-Blind, Two-Treatment, Two-Period, Crossover Study Investigating the Systemic Bioavailability of a Novel Cocrystal Ubiquinol Formulation Compared with a Ubiquinone Formulation in Healthy Adults.

Clinical studies indicate that different CoQ10 formulations have different absorption rates, highlighting research comparing their systemic bioavailability.


Increased bioavailability of ubiquinol compared to that of ubiquinone is due to more efficient micellarization during digestion and greater GSH-dependent uptake and basolateral secretion by Caco-2 cells.

The oral bioavailability of ubiquinol recently has been reported to be greater than that of ubiquinone in healthy adults.


The Cocrystal of Ubiquinol: Improved Stability and Bioavailability.

Compared to the oxidized form, ubiquinol has a much higher biological absorption and better therapeutic effect.


Physiologically-Based Pharmacokinetic Modeling of the Postbiotic Supplement Urolithin A Predicts its Bioavailability Is Orders of Magnitude Lower than Concentrations that Induce Toxicity, but also Neuroprotective Effects.

Solubility and dissolution kinetics are determined experimentally.


The potent in vitro antioxidant ellagitannins from pomegranate juice are metabolised into bioavailable but poor antioxidant hydroxy-6H-dibenzopyran-6-one derivatives by the colonic microflora of healthy humans.

However, the bioavailability of ellagitannins, including punicalagin, has not been previously described in humans.


Metabolism of antioxidant and chemopreventive ellagitannins from strawberries, raspberries, walnuts, and oak-aged wine in humans: identification of biomarkers and individual variability.

However, the microbial metabolite 3,8-dihydroxy-6H-dibenzo[b,d]pyran-6-one (urolithin B) conjugated with glucuronic acid was detected along the fractions F3-F5 in all of the subjects, independently of the consumed foodstuff.


Bioavailability of US commercial magnesium preparations.

The purpose of this study was to measure the bioavailability of four commercially-available preparations of magnesium, and to test the claim that organic salts are more easily absorbed.


L-Threonic Acid Magnesium Salt Supplementation in ADHD: An Open-Label Pilot Study.

Objective: Attention-deficit/hyperactivity disorder (ADHD) is estimated to affect up to 5% of adults worldwide.


Pharmacokinetics of β-Alanine Using Different Dosing Strategies.

The aim of this study is to objectify and understand the variation in plasma pharmacokinetics of a single oral β-alanine dose supplemented as either a fixed or a weight-relative dose (WRD) in an anthropometric diverse sample.


Genetic factors involved in modulating lutein bioavailability.

However, the bioavailability of the orally consumed lutein largely depends on its gastrointestinal absorption and subsequent metabolism which is in turn governed by various intrinsic and extrinsic factors.


Nutraceutical approach to enhance lutein bioavailability via nanodelivery systems.

Its bioavailability following consumption, however, depends on its rate of degradation.


Lutein and Zeaxanthin and Their Roles in Age-Related Macular Degeneration-Neurodegenerative Disease.

These carotenoids are concentrated by the action of specific binding proteins such as StARD3, which binds lutein, and GSTP1, which binds zeaxanthin and its dietary metabolite, mesozeaxanthin.


Improved Oral Absorption of Quercetin from Quercetin Phytosome®, a New Delivery System Based on Food Grade Lecithin.

Many beneficial properties have been described for quercetin, so much effort has been directed into overcoming the major drawbacks of this natural compound-its poor solubility and low oral absorption.


Does Encapsulation Improve the Bioavailability of Polyphenols in Humans? A Concise Review Based on In Vivo Human Studies.

Nevertheless, their bioactivity can be compromised due to their low bioavailability.


Plant-Derived Polyphenols in Cancer Therapy: Bridging Molecular Mechanisms and Bioavailability Toward Clinical Translation.

The clinical translation of polyphenols is still constrained by poor bioavailability, fast metabolism, low aqueous solubility and inefficient pharmacokinetic characteristics, which lead to insufficient systemic exposure and therapeutic efficacy despite strong preclinical data.


Bioavailability of magnesium diglycinate vs magnesium oxide in patients with ileal resection.

Patients who have undergone ileal resection are at risk for developing magnesium depletion/deficiency because of poor absorption and decreased intake as well as increased endogenous losses.


Intestinal Absorption and Factors Influencing Bioavailability of Magnesium-An Update.

Information on the bioavailability of the essential mineral Mg2+ is sparse.


Study of magnesium bioavailability from ten organic and inorganic Mg salts in Mg-depleted rats using a stable isotope approach.

Literature data on the bioavailability of various Mg forms provide scarce information on the best Mg salt to be used in animal and human supplementation.


Flavanol Bioavailability in Two Cocoa Products with Different Phenolic Content. A Comparative Study in Humans.

This study was aimed at assessing the absorption and metabolism of polyphenols in two soluble cocoa products: a conventional (CC) and a flavanol-rich product (CC-PP).


Influence of sugar type on the bioavailability of cocoa flavanols.

The beneficial effects of cocoa on vascular function are mediated by the absorption of monomeric flavanols into the circulation from the small intestine.


Bioavailability of flavan-3-ols and procyanidins: gastrointestinal tract influences and their relevance to bioactive forms in vivo.

There is considerable interest in the bioavailability of flavan-3-ols such as tea catechins and cocoa-derived procyanidin components of the diet and their bioactivity in vivo.


Pharmacokinetic properties and drug interactions of apigenin, a natural flavone.

Areas covered: This review summarizes and the absorption, distribution, metabolism and excretion (ADME) properties of apigenin, and drug-drug interaction of apigenin.


Flavones: Food Sources, Bioavailability, Metabolism, and Bioactivity.

The absorption and metabolism of flavones are also reviewed, in particular the intestinal absorption of both O- and C-glycosides.


Intestinal transport of dipeptides in man: relative importance of hydrolysis and intact absorption.

In each intestinal segment, amino acid absorption rates were significantly greater from the test solutions containing the same amount of amino acids in dipeptide than in free form(as high as 185% increase).


Investigating Genetic Determinants of Plasma Inositol Status in Adult Humans.

We aimed to investigate potential genetic regulation of circulating MI status and to evaluate correlation of MI concentration with other metabolites.


Myo-Inositol and Its Derivatives: Their Roles in the Challenges of Infertility.

Under physiological conditions, the MYO/DCI ratio is maintained at 40:1 in plasma.


Safety and efficacy of long-term nicotinamide mononucleotide supplementation on metabolism, sleep, and nicotinamide adenine dinucleotide biosynthesis in healthy, middle-aged Japanese men.

Obesity and aging are major risk factors for several life-threatening diseases.


Nicotinamide Mononucleotide Supplementation: Understanding Metabolic Variability and Clinical Implications.

Recent years have seen a surge in research focused on NAD+ decline and potential interventions, and despite significant progress, new discoveries continue to highlight the complexity of NAD+ biology.


Emerging strategies, applications and challenges of targeting NAD+ in the clinic.

Here, we summarize safety, bioavailability and efficacy data from NAD+-related clinical trials, focusing on aging and neurodegenerative diseases.


Exploring Secondary Amine Carnosine Derivatives: Design, Synthesis, and Properties.

However, carnosine's bioavailability in humans is lower than that in other mammals.


Acute preexercise supplementation of combined carnosine and anserine enhances initial maximal power of Wingate tests in humans.

However, upon oral ingestion, carnosine is readily degraded in human plasma by the highly active serum carnosinase-1 (CN1).


Non-hydrolyzed in digestive tract and blood natural L-carnosine peptide ("bioactivated Jewish penicillin") as a panacea of tomorrow for various flu ailments: signaling activity attenuating nitric oxide (NO) production, cytostasis, and NO-dependent inhibition of influenza virus replication in macrophages in the human body infected with the virulent swine influenza A (H1N1) virus.

In this article, the types of protection of carnosine in its bioavailable non-hydrolyzed forms in formulations are considered against reactive oxygen radical species-dependent injury, peroxynitrite damage, and other types of viral injuries in which impaired immune responses to viral pathogens are usually involved.


Review of the pharmacokinetics of French maritime pine bark extract (Pycnogenol®) in humans.

The basis for any in vivo activity is the bioavailability of constituents and metabolites of the extract.


Pycnogenol: a blend of procyanidins with multifaceted therapeutic applications?

As many studies indicate, pycnogenol components are highly bioavailable.


Bioactivity of dietary polyphenols: The role of metabolites.

However, polyphenols have a low oral bioavailability mainly due to an extensive biotransformation mediated by phase I and phase II reactions in enterocytes and liver but also by gut microbiota.


Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies.

Bioavailability differs greatly from one polyphenol to another, so that the most abundant polyphenols in our diet are not necessarily those leading to the highest concentrations of active metabolites in target tissues.


Interactions between gut microbiota and polyphenols: A mechanistic and metabolomic review.

However, due to their complex constituents and weak absorption, a convincing explanation for their remarkable bioactivity remains elusive for a long time.


The biological fate and bioefficacy of citrus flavonoids: bioavailability, biotransformation, and delivery systems.

Citrus flavonoids have limited bioavailability after oral administration, leaving the major part unabsorbed and persisted in the colon.


The Intestinal Fate of Citrus Flavanones and Their Effects on Gastrointestinal Health.

Evidence also indicates that they may impact the intestinal microbiome and are metabolized by the microbiota as well, thereby affecting their bioavailability.


Drug delivery and formulation development of hesperidin: a systematic review.

However, the clinical application of hesperidin is limited by its poor solubility, low bioavailability, and stability issues.


Effects of betaine on performance and body composition: a review of recent findings and potential mechanisms.

Betaine consumed from food sources and through dietary supplements presents similar bioavailability and is metabolized to di-methylglycine and sarcosine in the liver.


Safety of pyrroloquinoline quinone disodium salt as a novel food pursuant to Regulation (EC) No 258/97.

Information on the absorption, distribution, metabolism and excretion of PQQ in animals and humans is limited.


Safety assessment of a novel, dietary pyrroloquinoline quinone disodium salt (mnemoPQQ®).

Pyrroloquinoline quinone (PQQ), a potent coenzyme antioxidant naturally occurring in foods, has been demonstrated to protect brain cells by enhancing the expression of nerve growth factors (NGF) and NGF receptors, and suppressing the fibril formation and aggression of amyloid β.


Kinetics, pharmacokinetics, and regulation of L-carnitine and acetyl-L-carnitine metabolism.

Carnitine homeostasis is maintained by absorption from diet, a modest rate of synthesis, and efficient renal reabsorption.


Low Bioavailability and High TMAO Production: Novel Insights Into Acetylcarnitine and Carnitine Metabolism.

The food supplement acetylcarnitine is marketed for use in neurological support; however, research on its bioavailability and metabolic fate has been limited.


Folic acid and L-5-methyltetrahydrofolate: comparison of clinical pharmacokinetics and pharmacodynamics.

Studies comparing L-5-methyl-THF and folic acid have found that the two compounds have comparable physiological activity, bioavailability and absorption at equimolar doses.


Pharmacokinetics of Sodium and Calcium Salts of (6S)-5-Methyltetrahydrofolic Acid Compared to Folic Acid and Indirect Comparison of the Two Salts.

(6S)-5-Methyltetrahydrofolic acid ((6S)-5-Methyl-THF) salts and folic acid may differ in their abilities to raise plasma (6S)-5-Methyl-THF levels.


Fisetin-In Search of Better Bioavailability-From Macro to Nano Modifications: A Review.

As secondary plant metabolites, polyphenols are abundant in fruits and vegetables.


Fisetin: hormesis accounts for many of its chemoprotective effects.

Since these findings indicate that fisetin may have the potential to induce multi-system chemoprotective effects, it indicates the need to better clarify the absorption and bioavailability of fisetin and ways to enhance its efficiency.


Molecular mechanisms and therapeutic perspectives of luteolin on diabetes and its complications.

It regulates intestinal microenvironmental homeostasis, lipogenesis and catabolism, and the absorption of carbohydrates.


Administration of Pure Ergothioneine to Healthy Human Subjects: Uptake, Metabolism, and Effects on Biomarkers of Oxidative Damage and Inflammation.

After oral administration, ET is avidly absorbed and retained by the body with significant elevations in plasma and whole blood concentrations, and relatively low urinary excretion (<4% of administered ET).


Gene knockout and metabolome analysis of carnitine/organic cation transporter OCTN1.

The metabolome analysis of blood and several organs indicated complete deficiency of a naturally occurring potent antioxidant ergothioneine in octn1 ( -/- ) mice among 112 metabolites examined.


Effect of mushroom diet on pharmacokinetics of gabapentin in healthy Chinese subjects.

This study also investigated the concentrations of ergothioneine in plasma at baseline and following mushroom consumption.


Nutritional and Pharmacological Significance of Pomegranate (Punica granatum L): A Comprehensive Narrative Review.

While evidence supports the promising bioactivity of pomegranate compounds, their clinical application is hindered by low and variable bioavailability, inconsistent dosing and formulations, and limited data on adverse effects largely due to interindividual differences in gut microbiota metabolism of punicalagin into urolithins.


Soy protein isolate does not affect ellagitannin bioavailability and urolithin formation when mixed with pomegranate juice in humans.

We investigated the effect of mixing soy protein isolate and pomegranate juice (PJ) on the bioavailability and metabolism of ellagitannins (ETs) in healthy volunteers.


Bioavailability of Glucoraphanin and Sulforaphane from High-Glucoraphanin Broccoli.

The percentage of sulforaphane excreted in 24 h relative to the amount of glucoraphanin consumed varies among volunteers from 2 to 15%, but does not depend on the broccoli genotype.


Bioavailability of Sulforaphane Following Ingestion of Glucoraphanin-Rich Broccoli Sprout and Seed Extracts with Active Myrosinase: A Pilot Study of the Effects of Proton Pump Inhibitor Administration.

Gastric acidity appears to attenuate GR bioavailability, as evidenced by more SF and its metabolites being excreted after participants started taking omeprazole.


Broccoli or Sulforaphane: Is It the Source or Dose That Matters?

This review evaluates the current state of knowledge regarding the relationships between formulation (e.g., plants, sprouts, beverages, supplements), bioavailability and efficacy, and the doses of glucoraphanin and/or sulforaphane that have been used in pre-clinical and clinical studies.


Unraveling Anthocyanin Bioavailability for Human Health.

This review considers the bioavailability of health-protective anthocyanin pigments from foods, in light of the multiple molecular structures and complicated traffic patterns taken by anthocyanins both as flavonoid metabolites and as phenolic acid metabolites within the body.


Polyphenols and Human Health: The Role of Bioavailability.

Although an increasing number of trials have shown a correlation among polyphenol consumption and a reduction in risk factors for chronic diseases, discrepancies in explaining their positive effects have been found in terms of the bioavailability.


Anthocyanin-Rich Purple Plant Foods: Bioavailability, Antioxidant Mechanisms, and Functional Roles in Redox Regulation and Exercise Recovery.

Particular attention is given to their bioavailability and the challenges associated with their chemical stability, metabolism, and food matrix interactions.


Pharmacokinetics of L-carnitine.

In humans, the endogenous carnitine pool, which comprises free L-carnitine and a range of short-, medium- and long-chain esters, is maintained by absorption of L-carnitine from dietary sources, biosynthesis within the body and extensive renal tubular reabsorption from glomerular filtrate.


Carnitine and acylcarnitines: pharmacokinetic, pharmacological and clinical aspects.

The homeostasis of carnitine is multifaceted with concentrations achieved and maintained by a combination of oral absorption, de novo biosynthesis, carrier-mediated distribution into tissues and extensive, but saturable, renal tubular reabsorption.


Intestinal formation of trans-crocetin from saffron extract (Crocus sativus L.) and in vitro permeation through intestinal and blood brain barrier.

Trans-crocetin, a saffron metabolite originating from the crocin apocarotenoids, has been shown to exert strong NMDA receptor affinity and is thought to be responsible for the CNS activity of saffron.


Nanotechnological Approach to Increase the Antioxidant and Cytotoxic Efficacy of Crocin and Crocetin.

Their use as therapeutic agents is strongly compromised by a scarce stability, poor absorption, and low bioavailability.


Saffron carotenoids (crocin and crocetin) binding to human serum albumin as investigated by different spectroscopic methods and molecular docking.

Serum albumin has been known as the most important transporter of many drugs in the body that affects their disposition, transportation, and bioavailability.


Plasma changes in micronutrients following a multivitamin and mineral supplement in healthy adults.

To estimate the micronutrient (riboflavin, folate, vitamin C, vitamin B(12), iron, zinc and copper) bioavailability in healthy adults from a multi-micronutrient dietary supplement to assess the possible influence on it by the tablet disintegration properties and by the relative intestinal permeability of subject.


Pharmacokinetic Analyses of Liposomal and Non-Liposomal Multivitamin/Mineral Formulations.

Recent research supports previous contentions that encapsulating vitamins and minerals with liposomes help improve overall bioavailability.


Liposomal Mineral Absorption: A Randomized Crossover Trial.

The purpose of this analysis was to determine if a novel liposomal delivery mechanism improves mineral absorption from an MVM product.


Polyphenols: food sources and bioavailability.

The health effects of polyphenols depend on the amount consumed and on their bioavailability.


Seven days of oral taurine supplementation does not increase muscle taurine content or alter substrate metabolism during prolonged exercise in humans.

This study examined 1) the plasma taurine response to acute oral taurine supplementation (T), and 2) the effects of 7 days of T on muscle amino acid content and substrate metabolism during 2 h of cycling at approximately 60% peak oxygen consumption (VO2peak).


Plasma and platelet taurine are reduced in subjects with insulin-dependent diabetes mellitus: effects of taurine supplementation.

Plasma and platelet taurine concentrations were assayed in 39 patients with insulin-dependent diabetes mellitus (IDDM) and in 34 control subjects matched for age, sex, and both total and protein-derived daily energy intake.


Liposomal Formulation for Oral Delivery of Cyclosporine A: Usefulness as a Semisolid-Dispersion System.

This study aims to understand the process and mechanism of oral drug absorption from liposomes and to verify the usefulness of liposomal formulation for poorly soluble drugs.


New oral liposomal vitamin C formulation: properties and bioavailability.

In the paper, we present the new liposomal formulation of vitamin C free of harmful organic solvents.


Bioavailability of resveratrol.

This paper reviews our current understanding of the absorption, bioavailability, and metabolism of resveratrol, with an emphasis on humans.


Trans-Resveratrol Oral Bioavailability in Humans Using LipiSperse™ Dispersion Technology.

The primary hindrance towards resveratrol's therapeutic efficacy is its traditionally poor oral bioavailability.


Metabolism and pharmacokinetics of resveratrol and pterostilbene.

Beneficial properties of resveratrol and pterostilbene, a dimethyl ether analog of resveratrol, have attracted increasing interest in recent years.


Beneficial Effects of Spermidine on Ovarian Function, Gut Microbiota Composition, and Associated Metabolic Changes.

The results showed that dietary spermidine-rich feed significantly increased spermidine absorption and affected the metabolism of spermine and putrescine in the intestines.


Research progress on pharmacological effects and bioavailability of berberine.

However, factors such as poor solubility, low permeability, P-glycoprotein (P-gp) efflux, and hepatic-intestinal metabolism result in BBR having a low bioavailability (< 1%), which restricts its application in clinical settings.


Berberine as a multi-target therapeutic agent for obesity: from pharmacological mechanisms to clinical evidence.

Notably, BBR metabolites demonstrate pharmacological activity comparable to or exceeding that of the parent compound.


The Quest to Enhance the Efficacy of Berberine for Type-2 Diabetes and Associated Diseases: Physicochemical Modification Approaches.

Its poor bioavailability resulting from low intestinal absorption coupled with its efflux by the action of P-glycoprotein is, however, the major limitation.


Vitamin D bioavailability: state of the art.

Surprisingly, there is very little data on factors that affect absorption of this fat-soluble vitamin, although it is acknowledged that dietary vitamin D could help to fight against the subdeficient vitamin D status that is common in several populations.


Intestinal absorption of vitamin D: a systematic review.

Vitamin D is frequently prescribed as a supplement, yet its absorption remains poorly understood.


Comparison of the Effect of Daily Vitamin D2 and Vitamin D3 Supplementation on Serum 25-Hydroxyvitamin D Concentration (Total 25(OH)D, 25(OH)D2, and 25(OH)D3) and Importance of Body Mass Index: A Systematic Review and Meta-Analysis.

Two previous meta-analyses showed smaller differences between vitamin D3 and vitamin D2 in raising serum 25-hydroxyvitamin D [25(OH)D] and a consistently high heterogeneity when only including daily dosing studies.


A review of the potential benefits and limitations of oral glutathione supplementation.

Glutathione (GSH) plays an important role in the antioxidant defense and body detoxification system.


Glucosamine.

Following absorption of an oral dose, glucosamine is incorporated into plasma proteins during first-pass metabolism, resulting in 26% bioavailability.


Differentiation of patented crystalline glucosamine sulfate from other glucosamine preparations will optimize osteoarthritis treatment.

Only pCGS is given as a highly bioavailable once-daily dose (1500 mg), which consistently delivers the plasma levels of around 10 μmol/L required to inhibit interleukin-1-induced expression of genes involved in the pathophysiology of joint inflammation and tissue destruction.


Absorption, distribution and mechanism of action of SYSADOAS.

This review examines the data supporting oral absorption and body distribution of SYSADOA, and discusses their mechanism of action.


Clinical pharmacokinetics of N-acetylcysteine.

After an oral dose of N-acetylcysteine 200 to 400 mg the peak plasma concentration of 0.35 to 4 mg/L is achieved within 1 to 2 hours.


Next-Generation Microencapsulation Technologies for Probiotic Protection and Precision Delivery.

However, their therapeutic potential is limited by poor survival during oral delivery due to gastric acid, bile salts, and pathological gut conditions.


Natural sources and encapsulating materials for probiotics delivery systems: Recent applications and challenges in functional food development.

In addition to this, this paper also comprehensively discusses the factors affecting the probiotics viability and evaluation of successful release and survival of probiotics under simulated gastric, intestinal conditions as well as bile, acid tolerant conditions.


A thiolated oxidized guar gum and sodium alginate dual-network microspheres with enhanced gastric acid resistance and mucoadhesion for delivery of probiotics.

Probiotics offer numerous beneficial functions for human bodies, while the low survival rate under gastric acid and short retention time in the intestine are the major obstacles to their utilization.


A purified membrane protein from Akkermansia muciniphila or the pasteurised bacterium blunts colitis associated tumourigenesis by modulation of CD8+ T cells in mice.

Gut microbiota have been linked to inflammatory bowel disease (IBD) and colorectal cancer (CRC).


Introducing inulin-type fructans.

Supported by the results of a large number of animal studies and human nutrition intervention trials, the claim 'inulin-type fructans enhance calcium and magnesium absorption' is scientifically substantiated, but different inulin-type fructans have probably a different efficacy (in terms of effective daily dose), the most active product being the oligofructose-enriched inulin.


Fiber and prebiotics: mechanisms and health benefits.

The health benefits of dietary fiber have long been appreciated.


Pharmacokinetics of Nitrate and Nitrite Following Beetroot Juice Drink Consumption.

As BR juice can naturally contain both NO3 - and NO2 - the objective of this study was to evaluate the individual effects of NO3 - and NO2 - consumed from BR on plasma [NO3 -]/[NO2 -] and their subsequent effects on various cardiovascular measures.


Ageing modifies the oral microbiome, nitric oxide bioavailability and vascular responses to dietary nitrate supplementation.

This study evaluated whether changes in the oral microbiome in response to dietary nitrate and antiseptic mouthwash treatments were related to changes in nitric oxide bioavailability and vascular function.


Beetroot juice versus chard gel: A pharmacokinetic and pharmacodynamic comparison of nitrate bioavailability.

Here, we compare the plasma pharmacokinetics of NO3-, nitrite (NO2-), and total nitroso species (RXNO) following oral ingestion of either NO3- rich beetroot juice (BR) or chard gels (GEL) with the associated changes in blood pressure (BP).


Ultramicronized N-palmitoylethanolamine associated with analgesics: Effects against persistent pain.

Naïve PEA is a large particle size lipid molecule with low solubility and bioavailability.


Palmitoylethanolamide (PEA) as a Potential Therapeutic Agent in Alzheimer's Disease.

According to this view, preclinical studies indicate that PEA, especially in micronized or ultramicronized forms (i.e., formulations that maximize PEA bioavailability and efficacy), could be a potential therapeutic agent for the effective treatment of different pathologies characterized by neurodegeneration, (neuro)inflammation, and pain.


Effects of Palmitoylethanolamide on Neurodegenerative Diseases: A Review from Rodents to Humans.

The properties of PEA, especially of its micronized or ultra-micronized forms maximizing bioavailability and efficacy, have sparked a series of innovative research to evaluate its possible application as therapeutic agent for neurodegenerative diseases.