Tips archive

timing

Take vitamin D3 with fat, not water

D3 is fat-soluble. Absorption studies show ~30% higher serum 25(OH)D when co-ingested with the largest fatty meal of the day, versus fasted. Same principle applies to K2 and E.

timing

Magnesium in the evening, not the morning

Magnesium supports GABA activity and sleep architecture. Taking it 1-2 hours before bed captures the sleep benefit. Morning dosing wastes that effect and may cause daytime drowsiness.

combination

D3 without K2 may misdirect calcium

D3 raises calcium absorption. K2 (MK-7 preferred) helps direct that calcium to bone rather than arteries. Human hard-endpoint data is modest but plausible, K2 costs pennies, worth the hedge.

dose reality check

Most berberine RCTs use 500 mg three times daily

The blood glucose and lipid effects of berberine are reproducible at 1500 mg/day total, split across meals. Single-dose 500 mg products deliver about a third of that exposure. Read labels carefully.

biomarker

HOMA-IR is cheaper and often more useful than fasting glucose alone

HOMA-IR uses fasting glucose and fasting insulin together to estimate insulin resistance. Most primary care panels omit insulin. Order it. Insulin resistance shows up years before fasting glucose does.

behavior

Zone 2 three hours a week outperforms any NAD+ product on VO2max

Zone 2 training reliably raises VO2max in older adults over months, an outcome no supplement has come close to matching. If you can only do one thing for longevity, this is that thing.

debunk

The Blue Zones age validation problem

Recent analyses show many centenarian claims in Blue Zones regions lack birth records or come from pension-fraud-affected regions. The dietary conclusions drawn from them are weaker than the popular narrative implies.

study spotlight

NIH ITP 2024: rapamycin extended lifespan, most others didn't

The Interventions Testing Program tests longevity candidates in genetically diverse mice across three labs. Rapamycin has extended lifespan repeatedly. NMN, resveratrol, curcumin, and most polyphenols have not.

combination

Iron blocks polyphenol absorption

Iron and polyphenols (curcumin, resveratrol, EGCG, quercetin) bind in the gut. Separate them by 2-3 hours. Coffee and tea polyphenols also inhibit non-heme iron absorption meaningfully.

dose reality check

Curcumin is only useful in bioavailability-enhanced form

Standard curcumin is under 1% bioavailable. Look for products with piperine, phytosome (Meriva), micronized (Longvida), or nano-particle formulations. Otherwise most of your capsule leaves in feces.

biomarker

The Omega-3 Index is one of the strongest mortality predictors

An 8%+ Omega-3 Index (percentage of EPA+DHA in red blood cell membranes) associates with roughly 5 years longer life expectancy vs under 4%. Home fingerstick tests are cheap.

timing

Creatine timing barely matters, dosing consistency does

The old post-workout dogma is largely gone. What matters is taking 3-5 g/day every day. Whether you take it with breakfast, dinner, or in a workout shake is roughly equivalent.

behavior

Sleeping in a 65-67 F (18-19 C) room measurably improves sleep quality

Body temperature drops during sleep. A cooler ambient temperature supports that drop. Both objective sleep architecture and subjective quality improve at these temperatures.

study spotlight

The PEARL rapamycin trial found no functional benefit at 1 year

PEARL is the largest human longevity-dosed rapamycin RCT so far. Primary outcome (lean muscle mass) did not improve. Some secondary outcomes suggested modest benefit. Not a slam-dunk positive.

combination

NAD+ precursors and CD38 inhibitors are commonly paired

CD38 consumes NAD+ and rises with age. Apigenin and quercetin inhibit CD38 in animals. Pairing an NAD+ precursor with a CD38 inhibitor is a common longevity stack, though human evidence for the pairing is preclinical.

dose reality check

Fish oil oxidation is common in mass-market products

Oxidized fish oil provides less benefit and may be pro-inflammatory. Tested by independent lab products with low peroxide values, and refrigerated liquid formulations, are more reliable.

behavior

Sauna 4-7 sessions per week associates with lower cardiovascular mortality

Finnish cohort data (Laukkanen 2015) shows a strong dose-response between sauna frequency and lower all-cause and cardiovascular mortality. Observational, but the effect size is very large.

debunk

Antioxidant supplements do not prevent cancer

Large trials (ATBC, CARET, SELECT) showed antioxidant supplementation, at pharmacological doses, did not reduce cancer incidence and in some cases increased it. Diet-based antioxidants are different from megadoses.

biomarker

ApoB is a better cardiovascular risk marker than LDL-C

ApoB counts the number of atherogenic particles. LDL-C measures cholesterol carried in them. Two people with the same LDL-C can have very different ApoB. Ask for ApoB by name.

combination

Statin plus CoQ10 has thin RCT evidence but a plausible rationale

Statins reduce endogenous CoQ10 synthesis. Whether that matters clinically is debated. Meta-analyses of CoQ10 supplementation in statin users show mixed results on muscle symptoms. Low-cost hedge if symptoms present.

study spotlight

The MILES trial: metformin altered gene expression, but so does exercise

Metformin in older adults shifted muscle gene expression toward a youthful pattern. But another arm of the same research group showed metformin blunted the exercise adaptation response. Tradeoffs.

timing

Berberine before high-carb meals blunts postprandial glucose

Taking berberine 15-30 minutes before a meal that contains starch reduces the postprandial glucose peak more than after-meal dosing. Practical for people using berberine for glycemic control.

dose reality check

Ashwagandha needs to be a standardized extract, not raw powder

The RCTs showing anxiolytic and cortisol effects use KSM-66 or Sensoril extracts standardized to withanolides. Generic root powder from bulk suppliers is much weaker per gram and inconsistently characterized.

behavior

Grip strength is one of the strongest single mortality predictors past 60

PURE study (140k adults, 17 countries) found grip strength was a stronger predictor of cardiovascular mortality than systolic blood pressure. Cheap to measure. Resistance training raises it.

debunk

Collagen peptides are not magically absorbed intact

Collagen peptides are digested to amino acids and small dipeptides like proline-hydroxyproline. Some intact dipeptides do reach circulation. But the marketed idea that oral collagen directly becomes skin collagen is oversimplified.

combination

Coffee blunts iron absorption significantly

Drinking coffee within one hour of an iron-containing meal or iron supplement can reduce iron absorption by 60% or more. Space them by 1-2 hours. Same for tea.

biomarker

GrimAge is the best-validated epigenetic clock so far

Among the family of epigenetic age clocks (Horvath, Hannum, PhenoAge, GrimAge), GrimAge shows the strongest correlations with hard endpoints like all-cause mortality and time-to-death. But it is still a research tool.

study spotlight

The DO-HEALTH trial: multi-nutrient supplementation, mostly null

DO-HEALTH tested vitamin D, omega-3, and strength exercise in 2000+ older adults. Modest positive effect from exercise. Small effect on infection rate from omega-3. No effect on most other endpoints.

timing

Melatonin dose does not need to be high

Sleep-onset improvement occurs at 0.3-0.5 mg. Common OTC doses of 3-10 mg raise serum melatonin to 50x physiological levels, which may worsen next-day residual effects. Low dose is often more effective.

dose reality check

Third-party testing means one specific product batch, not the brand

USP, NSF, and Informed Choice certifications apply to specific batches or product lines. A brand can have some certified products and some uncertified. Verify the exact product, not just the brand.

behavior

Late caffeine cuts deep sleep even when you fall asleep fine

Caffeine up to 6 hours before bed reduces slow-wave sleep and total sleep time by measurable amounts, even in people who report no subjective sleep disturbance. Half-life is 5-7 hours in most adults.

combination

Magnesium and zinc compete for absorption at high doses

Separate high-dose zinc (over 30 mg) from magnesium by at least 2 hours. At typical multivitamin doses (10-15 mg zinc, 100-200 mg magnesium) this matters much less.

study spotlight

The VITAL trial: vitamin D reduced cancer mortality in select subgroups

VITAL was a 26,000-person, 5-year RCT of 2000 IU/day D3 and 1 g/day omega-3. Cancer mortality reduction in extended follow-up. No effect on cardiovascular events, no effect on fracture in D3 arm.

biomarker

Fasting insulin is more informative than fasting glucose in early metabolic dysfunction

By the time fasting glucose is elevated, insulin resistance is often years advanced. Fasting insulin rises first. A fasting insulin under 5 uIU/mL is a reasonable target for metabolic health.

debunk

Alkaline water does not detoxify or change blood pH

Blood pH is tightly regulated at 7.35-7.45 regardless of water intake. Alkaline water may briefly affect urinary pH. That is not a longevity mechanism. Marketing claims outpace evidence considerably.

behavior

The single best inflammation marker to track is hs-CRP

High-sensitivity C-reactive protein above 3 mg/L associates with elevated cardiovascular risk. Below 1 mg/L is optimal. Chronic elevation without acute infection is worth investigating.

combination

Vitamin C blunts strength gains when taken pre-workout in high doses

High-dose vitamin C (over 1 g) taken before resistance training blunts the training-induced adaptation, likely by reducing helpful reactive oxygen signaling. Take vitamin C at other times of day.

dose reality check

Rhodiola RCTs mostly use SHR-5 extract, standardized to rosavins and salidrosides

Generic rhodiola root products vary wildly in active content. Trials of adaptogenic effects use SHR-5 or comparable standardized extracts. Look for standardization to 3% rosavins and 1% salidrosides.

timing

Time-restricted eating is not more effective than caloric restriction, but easier

Recent RCTs (TREAT, TREAT-Diabetes) show 16:8 time-restricted eating produces weight and metabolic changes similar to isocaloric standard eating. The value is adherence, not metabolic magic.

study spotlight

REDUCE-IT: high-dose EPA cut cardiovascular events, EPA+DHA in STRENGTH did not

REDUCE-IT used 4 g/day of pure EPA ester (icosapent ethyl) and cut major cardiovascular events by 25%. STRENGTH used EPA+DHA carboxylic acid at similar total dose and showed no benefit. The difference is not fully explained.

supplementation

Magnesium was tested with fluoxetine in 40 adults with depression

This randomised study tested magnesium as an add-on to fluoxetine in 40 outpatients aged 18 to 50 years with depression in Makassar, Indonesia. Twenty participants continued fluoxetine alone for 6 weeks and 20 received fluoxetine plus 350 mg of oral magnesium once daily.

supplementation

A post hoc analysis examined 60 days of NMN in 80 healthy adults

This was a post hoc analysis of a randomised, double-blind clinical trial in healthy middle-aged participants. The parent trial compared daily nicotinamide mononucleotide at 300, 600 or 900 mg with placebo for 60 days. The analysis included 80 people with a mean age of 49.4 years.

supplementation

The largest human evidence base of any longevity molecule: 92 of 137 RCTs pos...

A systematic review pulled every published randomised controlled trial on pure resveratrol and found 137 studies covering 104 unique RCTs and more than 4,800 people.

supplementation

In 23 normal-weight adults, hydrolysed jaboticaba powder increased urinary urolithin excretion by up to 69% over 48 hours

This randomised crossover clinical trial studied 23 normal-weight adults after a single 3 g capsule dose of jaboticaba peel and seed powder. Participants received either non-hydrolysed powder or acid-hydrolysed powder, separated by a 14-day washout.

supplementation

A trial established urolithin A's human evidence base

This is the trial that established urolithin A's human evidence base. Run by Amazentis (the company behind Mitopure) with academic co-authors including Johan Auwerx at EPFL, it registered as NCT03464500.

supplementation

RIPE compares 300 mg and 1,000 mg/day resveratrol with placebo for 24 months

RIPE is one of the longer-duration resveratrol trials on record. It compares 300 mg per day and 1,000 mg per day against placebo for 24 months, with cognitive and physical performance as primary endpoints, in older ad...

supplementation

The mechanism marketed as the longevity effect: 11 RCTs pooled show no signif...

This is the single most important paper for anyone deciding whether to buy resveratrol as an anti-aging supplement.

mechanism

A companion meta-analysis assessed NMN and metabolic outcomes

This review, led by researchers at the University of Hong Kong and Chinese University of Hong Kong, is the companion meta-analysis to Zhang et al.

research

The foundational 2017 paper from NIH's National Institute on Aging that first...

This is the original identification study behind the fucoidan-SIRT6 story. Researchers at the National Institute on Aging (part of NIH), working with the University of Eastern Finland and Ireland's Teagasc Food Resear...

mechanism

A meta-analysis included 12 NMN RCTs with 513 participants

Zhang, Poon, and Wong screened 4,049 records and included 12 randomised controlled trials with 513 total participants.

supplementation

A review tabulated resveratrol's inflammatory and immune endpoints in human trials

This is a table-heavy review of what resveratrol has actually done to inflammatory markers and immune endpoints in human trials.

mechanism

A systematic review evaluated NMN's effects on physical performance and safety

Wen and colleagues reviewed randomised controlled trials testing NMN's effect on physical performance and safety. The review's stated purpose was to evaluate both effect and safety profile of NMN supplementation.

supplementation

Higher dietary spermidine intake over one year tracked with better liver and cardiometabolic markers in 2,664 adults, without proving cause

This longitudinal analysis used baseline and one-year data from 2,664 PREDIMED-Plus participants who were older, overweight or obese, and had metabolic syndrome. It assessed dietary spermidine intake with a semi-quantitative food-frequency questionnaire rather than assigning a spermidine supplement.

supplementation

A pilot tested creatine with resistance training in colorectal-cancer survivors

This pilot trial tested whether creatine monohydrate could be added to a hybrid resistance-training programme for people previously treated for colorectal cancer.

research

Fisetin and training were tested in 44 obese men

Forty-four obese adult men completed a 12-week, four-arm randomised trial of placebo, fisetin alone, concurrent interval resistance-aerobic training with placebo, or the same training with fisetin. Fisetin was given at 200 mg/day.

supplementation

Nicotinamide riboside was tested for 4 weeks in people with psoriasis

This placebo-controlled study examined nicotinamide riboside (NR) in people with mild-to-moderate psoriasis. Participants received oral NR 500 mg twice daily or matching placebo for four weeks, with blood collected before and after supplementation.

supplementation

In 44 men with obesity, taurine plus exercise improved reported adipokines and body composition after 12 weeks, but the trial was small

This supplement-blinded, randomised, placebo-controlled trial allocated 44 men with obesity, defined as BMI at least 30 kg/m2, to four groups of 11: placebo control, taurine alone, exercise plus placebo, or exercise plus taurine. Taurine was given at 3 g/day for 12 weeks.

research

In 52 adults with autism, quercetin did not significantly outperform placebo on the main social-responsiveness comparison after 60 days

This randomised, triple-blind, placebo-controlled trial assigned 52 adults with autism spectrum disorder to quercetin or placebo for 60 days. Social Responsiveness Scale scores, WHO Quality of Life domains and other clinical measures were assessed at baseline, 30 days and 60 days.

supplementation

Omega-3 was tested during weight loss in 34 peri- or postmenopausal women

This pilot study randomised 34 peri- or postmenopausal women with body mass index at least 28 kg/m² to 3.25 g/day of omega-3 fatty acids or placebo during a behavioural weight-loss intervention. Median weight change was 10% below baseline.

supplementation

In 70 radiotherapy patients with head and neck cancer, ALA cut severe oral mucositis from 41.3% to 16.7%

This randomised controlled study enrolled 70 people with head and neck cancer receiving definitive radiotherapy. Participants took oral alpha-lipoic acid (ALA), 600 mg twice daily, or placebo throughout radiotherapy.

supplementation

Polyphenol mixture containing 133 mg resveratrol raised LDL cholesterol 9.5% ...

The PolyPAUSE trial gave 90 mildly hypercholesterolemic postmenopausal women a daily polyphenol mixture for 8 weeks: ellagitannins plus ellagic acid at 312 mg, resveratrol at 133 mg, and isoflavones at 166 mg. A 4-week washout and an 8-week placebo period followed. 78 women completed. The lipid results run in two directions at once.

supplementation

Meriva lowered gastric mucosal IL1β at 6 months in 50 high-risk patients

This double-blind phase IIa trial enrolled people in Puerto Rico and Honduras with Helicobacter pylori-negative gastric premalignant conditions: multifocal atrophic gastritis or gastric intestinal metaplasia. Fifty of 110 screened participants were randomised 1:1 to 1,000 mg/day of the curcumin formulation Meriva or placebo for 6 months; 48 completed the trial.

supplementation

Coenzyme Q10 and taurine were tested in 24 adolescent soccer players

This randomised, double-blind, placebo-controlled trial assigned 24 male under-19 soccer players, mean age 17.9 years, to placebo, coenzyme Q10, or taurine for 14 days. Each group had eight participants. The coenzyme Q10 dose was 300 mg/day. Taurine was given at 4 g/day plus 4 g before each of three 90-minute soccer-match simulations.

supplementation

Magnesium oxide was tested for 12 months in 247 adults with type 2 diabetes

This 12-month randomised, double-blind, placebo-controlled trial evaluated magnesium oxide in adults with type 2 diabetes, HbA1c at least 7.0%, and creatinine clearance above 30 mL/min. The 247 participants in the intention-to-treat analysis received magnesium oxide 500 mg, providing 302 mg elemental magnesium (n=118), or placebo (n=129).

supplementation

In 103 older adults, 16 weeks of high-speed resistance training improved seve...

This six-arm randomised trial assigned 103 community-dwelling older adults, mean age 68.2 years, to elastic-band or water-based high-load, velocity-intentional resistance training, each with creatine or placebo, or non-training control with creatine or placebo. Training lasted 16 weeks, three 60-minute sessions per week. Creatine intake was 3 g daily.

supplementation

In a 40-person pilot, krill oil raised the omega-3 index; pain findings were ...

This 12-week double-blind, randomised, placebo-controlled pilot enrolled 40 community-dwelling adults aged 60 years or older with moderate chronic musculoskeletal pain. Participants received either 4 g/day of krill oil, providing 1,288 mg EPA plus DHA, or placebo.

supplementation

Spermidine was well tolerated for 13 weeks in 40 older adults after vaccination

This double-blind, randomised, placebo-controlled pilot enrolled 40 healthy adults older than 65 years after their third SARS-CoV-2 vaccine dose. Participants took 6 mg of oral spermidine daily for 13 weeks. The abstract reports that supplementation was well tolerated.

supplementation

Taurine was tested with a conditioning protocol in 20 elite male wrestlers

This double-blind crossover study tested taurine alongside post-activation performance enhancement in 20 elite male wrestlers. Each athlete completed three sessions: control with neither supplementation nor the conditioning protocol, the protocol with sucrose placebo, and the protocol with taurine.

supplementation

In 11 young men, 1,200 mg/day NMN reduced some exercise-induced inflammatory ...

Eleven untrained men, mean age 22.8 years, completed a randomised, placebo-controlled, counterbalanced crossover study. They took placebo or NMN at 1,200 mg/day for 7 days, separated by a 3-week washout, then performed blood-flow-restriction resistance exercise. Multiple muscle biopsies were taken before and after exercise.

supplementation

EPA plus DHA were tested for 30 months in 240 statin-treated coronary patients

This secondary analysis used a randomised trial of 240 patients with stable coronary artery disease who were taking statins. Participants received 3.36 g/day of EPA plus DHA or no supplement for 30 months.

supplementation

Nicotinamide riboside was tested for 12 weeks in 42 adults with mild cognitive impairment

This phase II pilot was a 12-week, double-blind, randomised, placebo-controlled study of nicotinamide riboside in adults with amnestic mild cognitive impairment. Forty-two participants completed treatment: 22 received nicotinamide riboside and 20 placebo.

supplementation

A phase 3 trial compared immunonutrition with standard nutrition in 203 bladder-cancer patients

SWOG S1600 was a multicentre, double-blind phase 3 trial at 13 US academic and community sites. It randomised 203 adults with bladder cancer scheduled for radical cystectomy to standard oral nutrition or an immunonutrition drink containing added l-arginine, omega-3 fatty acids, and dietary nucleotides. Drinks were taken three times daily for 5 days before and after surgery.

supplementation

A trial compared alpha-lipoic acid, pregabalin and their combination in 151 adults

This 12-week, phase IV multicentre trial enrolled 151 people with type 2 diabetes and painful diabetic peripheral neuropathy. Participants were allocated 1:1:1 to alpha-lipoic acid (ALA) 480 mg/day, pregabalin 150 mg/day, or their combination. The primary endpoint was change from baseline in visual analogue scale pain score.

supplementation

This was not a curcumin trial: 10 infected eastern indigo snakes received SLU...

Curcumin appears in this abstract only among treatments that had previously failed to eliminate Cryptosporidium serpentis in eastern indigo snakes. The intervention tested here was SLU-2633, a triazolopyridazine analogue, not curcumin. Ten naturally infected eastern indigo snakes were randomly divided into two groups of five.

supplementation

A 12-week trial compared 2 diets in 40 adults with rheumatoid arthritis

This 12-week dietary randomised trial enrolled 40 adults with rheumatoid arthritis in Ireland. Twenty were assigned to a Mediterranean diet and 20 to the Irish Healthy Eating Guidelines. Dietary Inflammatory Index scores were calculated from food diaries, with the energy-adjusted index, e-DII, as the main reported dietary measure.

supplementation

In 18 healthy adults, flaxseed and corn oil did not show a consistent post-me...

This double-blind, randomised four-way crossover trial tested acute inflammatory responses to meals with different fat sources. Eighteen healthy adults ate isocaloric 706 kcal test meals containing 40 g fat from butter, coconut oil, flaxseed oil or corn oil. Blood was collected for six hours after each meal.

supplementation

In 72 healthy adults, 1.1 g/day omega-3 from krill oil raised plasma EPA and ...

This double-blind randomised trial compared krill oil with fish oil in 72 healthy adults, including 53 women and 19 men. Thirty-six participants received each product for 12 weeks. Both groups received 1.1 g/day of omega-3 fatty acids.

supplementation

High-dose DHA was tested for 24 months in 365 older adults without dementia

This phase IIa trial tested high-dose DHA in adults aged 55-80 years without dementia who had low dietary DHA intake. The 24-month study at the University of Southern California was randomised, double-blind and placebo-controlled. Of 739 people screened, 365 were randomised: 181 to the LP arm and 184 to the no-LP arm.

supplementation

A 2-year pilot tested resveratrol plus TA-65 in 120 healthy adults

The PBAR pilot trial followed 120 healthy people with a mean age of 71.7 ± 4.6 years for two years. It primarily aimed to develop a trial-design method based on NT-proBNP-derived "proBNPage", a surrogate for biological age. Participants were assigned to coenzyme Q10 100 mg twice daily plus selenium 100 mcg, resveratrol 350 mg twice daily plus TA-65 100 U, or placebo.

supplementation

A 7-day pilot tested 3.50 g and 8.75 g/day omega-3 in 84 severe-pneumonia patients

This pilot study sought a tolerable omega-3 dose for enterally fed patients with severe community-acquired pneumonia. Eighty-four patients were randomly assigned to a control group or experimental groups receiving 3.50 g or 8.75 g/day of EPA plus DHA for seven days.

supplementation

Creatine was tested for 6 months in 50 people with Down syndrome

This double-blind trial enrolled 50 people with Down syndrome and compared oral creatine with dextrose placebo. Creatine was given at 20 g/day for 5 days, then 5 g/day for 6 months. Dual-energy X-ray absorptiometry measured body composition, while renal and hepatic laboratory markers were checked at baseline and six months. After 6 months, the creatine group had a significa...

supplementation

In 16 haemodialysis patients, 6 weeks of creatine in dialysate raised circula...

A small placebo-controlled pilot examined creatine added to dialysate during haemodialysis. Sixteen patients aged 27 to 78 years completed the study, including nine women. Four sequential groups received 0.5, 1.0, 1.5 or 2.0 mmol/L creatine in dialysate for 6 weeks; within each group, block randomisation allocated creatine or placebo in a 3:1 ratio. The main outcomes were p...

supplementation

A single 2,000 mg magnesium-oxide dose did not raise short-term systemic expo...

This randomised, open-label pharmacokinetic study examined absorption after a single oral dose of magnesium oxide in 24 healthy men aged 18-45 years. Twelve received 750 mg and 12 received 2,000 mg. Serum magnesium was measured from baseline through 12 hours, and the investigators calculated Cmax, Tmax and AUC0-12.

supplementation

Omega-3 was tested around bariatric surgery in 58 patients

This triple-blind randomised trial enrolled 58 people undergoing bariatric surgery, 81% of them women, with mean age 38.2 years and mean body mass index 41.1 kg/m². Participants received 2,000 mg/day of EPA plus DHA or sunflower-oil placebo for 90 days: 15 days before surgery and 75 days afterwards.

supplementation

A 12-day pilot tested lutein, zeaxanthin and omega-3 in 16 adults

This randomised, non-blinded, controlled pilot enrolled 16 adults, 10 men and six women, with a mean age of 31.38 years. After a 7-day washout, nine participants took lutein plus zeaxanthin at 12 mg/day for 12 days. Seven took the same carotenoid supplement plus 900 mg/day omega-3, providing 540 mg EPA and 360 mg DHA.

supplementation

Omega-3 was tested for 6 months in 102 dry-eye patients with a low omega-3 index

Investigators randomised 102 people with dry eye and an omega-3 index below 4%. Participants received omega-3 capsules or olive-oil placebo twice daily for six months. Each omega-3 capsule contained 325 mg eicosapentaenoic acid and 175 mg docosahexaenoic acid; participants took four capsules at each dosing time.

research

A 500 mg/day quercetin bar reduced acute mountain-sickness prevalence from 25...

A double-blind, placebo-controlled trial tested quercetin prophylaxis during rapid ascent in 110 healthy lowland men aged 20-40 years. Participants travelled from 440 m to 3,048 m for six days and then to 3,750 m.

supplementation

Intravenous magnesium sulfate was tested in 265 cardiac-surgery patients

This single-centre, double-blind, randomised, placebo-controlled trial tested perioperative intravenous magnesium sulfate in adults having coronary artery bypass grafting and/or valvular surgery. Patients with prior atrial arrhythmias or severe renal dysfunction were excluded.

supplementation

Omega-3 intake was examined against 5 serum markers in 510 older adults with metabolic syndrome

This analysis used 510 older Spanish adults with metabolic syndrome from PREDIMED-Plus. It examined whether reported habitual omega-3 intake tracked five serum markers related to atrial-fibrillation pathways over 5 years: NT-pro-BNP, high-sensitivity troponin T, C-reactive protein, PICP and 3-nitrotyrosine.

supplementation

Krill oil had higher 72-hour EPA+DHA bioavailability than fish oil, but krill meal and fish…

This crossover trial in 15 healthy subjects compared 72-hour bioavailability of EPA+DHA from krill oil (1,400 mg EPA+DHA), krill meal (1,102 mg), and fish oil (1,455 mg). The incremental area under the curve for plasma phospholipid EPA+DHA was significantly higher after krill oil (89.08%) than after fish oil (59.15%, P=0.003) or krill meal (44.97%, P<0.001).

supplementation

4 g/day purified EPA (icosapent ethyl) reduced cardiovascular events by 25% in statin-treated…

REDUCE-IT randomized 8,179 statin-treated patients with elevated triglycerides (135-499 mg/dL) to 4 g/day icosapent ethyl (purified EPA ethyl ester) or mineral oil placebo. Over 4.9 years median follow-up, the primary composite endpoint (cardiovascular death, nonfatal MI, nonfatal stroke, coronary revascularization, or unstable angina) occurred in 17.2% vs 22.0% (HR 0.75, 95...

supplementation

Higher Omega-3 Index (EPA+DHA in red blood cells) was associated with 34% lower all-cause…

The Framingham Heart Study Offspring cohort (n=2,500, mean age 66, free of CVD at baseline) was followed for 7 years. The Omega-3 Index (EPA+DHA as percentage of red blood cell membrane fatty acids) was measured at baseline.

supplementation

4 g/day EPA+DHA carboxylic acid (Epanova) showed no cardiovascular benefit vs corn oil and was…

STRENGTH randomized 13,708 statin-treated patients with high cardiovascular risk and hypertriglyceridemia to 4 g/day of omega-3 carboxylic acid (EPA+DHA, Epanova) or corn oil placebo. The primary composite endpoint (CV death, nonfatal MI, nonfatal stroke, coronary revascularization, unstable angina) occurred in 12.0% vs 12.2% (HR 0.99, 95% CI 0.90-1.09, P=0.84).

research

Two-year multivitamin supplementation slowed biological aging measured by DNA methylation…

An analysis led by Mass General Brigham investigators found that daily multivitamin supplementation over two years was associated with slowing of biological aging as measured by DNA methylation age (DNAmAge). This is one of the first long-duration RCTs to use epigenetic clocks as a primary endpoint for a common supplement.

research

Largest single-cell aging atlas to date reveals aging is synchronized across organs, not…

A 7-million-cell atlas mapping aging across 21 organs revealed that aging is a synchronized, body-wide process. This is the largest single-cell study of aging to date. The finding that aging proceeds in a coordinated fashion across organs has implications for supplement design: interventions targeting a single pathway in one tissue may be insufficient if the aging process is...

research

In a cohort of 4,260 health enthusiasts, a delayed-release calcium-alpha-ketoglutarate plus…

Researchers led by Brian K. Kennedy analyzed 4,260 individuals who purchased saliva-based DNA epigenetic tests between 2020 and 2025 and completed detailed lifestyle and supplement questionnaires. Seventy-one percent of the cohort reported supplement use.

research

In 26 hospitalized patients with COVID-19 ARDS, Wharton’s Jelly MSCs were well tolerated but…

Torres and colleagues report the COVIDMES multicenter Phase I/II pilot trial of Wharton’s Jelly-derived mesenchymal stromal cells in hospitalized patients with moderate-to-severe COVID-19 ARDS. Twenty-six patients were enrolled and 25 received two intravenous doses: 13 received 1×10^6 viable cells per kilogram and 12 received placebo.

research

A one-month randomized vegan diet intervention shifted inflammatory pathways and slowed…

Karbacher and colleagues analyzed genome-wide DNA methylation after a one-month randomized, isocaloric vegan versus meat-rich diet intervention in 48 healthy adults. The vegan group showed more differentially methylated positions in promoter regions linked to cancer-related pathways, cell growth, mTOR, and Hippo signaling.

research

Loneliness, depression, and stress were each associated with faster epigenetic aging across 22…

Guo and colleagues reviewed 22 studies of psychological adversity and DNA-methylation age acceleration from midlife onward. Fifteen studies met the review’s high-quality classification. The pooled associations were consistent for second-generation clocks, especially PhenoAge and GrimAge.

research

PUBLIC REACTION: Bryan Johnson says data on sleeping with a partner are mixed and asks…

On 11 August 2026, Bryan Johnson posted that data on sleeping with a partner are mixed: some people sleep better and others do not. He asked followers to describe their experience. The post responds to public discussion of his separate sleeping arrangements and his emphasis on maximizing sleep scores.

research

27 studies (n=597) found hydrogen supplementation improved lower-limb explosive power and…

A 2024 meta-analysis of 27 publications (597 participants) evaluated molecular hydrogen supplementation for physical performance. H2 improved lower-limb explosive power (SMD=0.30, p=0.018, I2=0%), reduced rating of perceived exertion during exercise (SMD=-0.37, p=0.009, I2=58.0%), and reduced blood lactate (SMD=-0.37, p=0.001, I2=22.0%).

research

13 RCTs (n=757) found hydrogen-rich water reduced total cholesterol by 6.71 mg/dL and LDL by…

A 2026 systematic review and meta-analysis analyzed 13 RCTs (n=757 participants) of hydrogen-rich water in adults with BMI >=25. HRW significantly reduced total cholesterol (WMD: -6.71 mg/dL, 95% CI: -10.38 to -3.04, p<0.001) and LDL-C (WMD: -3.21 mg/dL, 95% CI: -6.31 to -0.10, p=0.043). Effects on triglycerides and HDL-C were not significant.

research

6 months of hydrogen-rich water preserved telomere length and increased TET2 expression in…

40 adults aged 76.0 +/- 5.6 years were randomized to drink 0.5 L/day of hydrogen-rich water (15 ppm H2) or control water for 6 months. The HRW group preserved telomere length (baseline 0.99 +/- 0.15, follow-up 1.02 +/- 0.26) while controls showed shortening (baseline 0.92 +/- 0.27, follow-up 0.79 +/- 0.15), treatment-by-time interaction p=0.049.

supplementation

Meta-analysis of 5 RCTs (n=236) found urolithin A supplementation improved 6-minute walk test…

This systematic review and meta-analysis pooled 5 randomized controlled trials (total n=236 participants) examining urolithin A supplementation and muscle health outcomes. The review was registered with PROSPERO and used Cochrane RoB 2 for risk of bias and GRADE for certainty. Quantitative meta-analysis was possible only for the 6-minute walk test (6MWT).

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Berberine 1g/day for 6 months reduced body fat and liver fat in 337 adults with obesity and…

The BRAVO trial randomized 337 diabetes-free adults with obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) to 1g/day berberine or placebo for 6 months across 11 Chinese hospitals. Mean age was 41.8 years, 65.6% male. The primary outcome was relative percentage change in visceral fat area. The trial was analyzed by intention-to-treat.

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Metformin increased antioxidant signaling and reduced lipid peroxidation in rat neurons…

Jorge Arriagada and colleagues studied metformin in primary fetal rat hippocampal neurons exposed to soluble amyloid-beta oligomers. Cultures received metformin at 2.5 mM for 24 hours before a 6-hour exposure to amyloid-beta oligomers at 500 nM. Metformin promoted nuclear accumulation of Nrf2 and preserved the Nrf2/KEAP1 profile under amyloid stress.

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Early-life sugar rationing was linked to lower adult cancer incidence, longer leukocyte…

Chen Zhu and Weilong Zhang used the abrupt end of United Kingdom sugar rationing in September 1953 as a natural experiment. They studied 64,761 UK Biobank participants born from 1951 to 1956. Participants whose first 1,000 days fell under rationing had lower adult cancer incidence at several sites.

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PUBLIC REACTION: Johnson says he is energized by debate after the Ross Douthat interview; the…

On 18 August 2026, Bryan Johnson wrote that he is energized to see Don’t Die being processed by society. He referred to public discussion of living longer and disease-free lives after Ross Douthat’s New York Times interview. The post contains no new measurement, intervention, dose, adverse event, or outcome.

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A stacked DNA-methylation survival model trained in the Framingham Heart Study outperformed…

Muthukumar Yugan Gogul, Karthikeyan Vijayakumar, and Gwang-Won Cho present a stacked survival model built from DNA-methylation data in the Framingham Heart Study. Five complementary survival models were fused with a neural-network meta-learner.

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Across 16 RCTs and 492 adults, creatine monohydrate improved memory (SMD = 0.31, 95% CI 0.18…

Chen Xu and colleagues pooled 16 randomised controlled trials covering 492 adults aged 20.8 to 76.4 years. All trials used creatine monohydrate. Doses across the included studies ranged from 3 g/day to 20 g/day, plus weight-based dosing at 0.3 g/kg/day. Durations ranged from a single 7.5-hour test window to 18 months.

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Across 35 RCTs and 1,192 participants, creatine raised lean body mass by 0.68 kg overall (95%…

Felipe Delpino and colleagues searched PubMed, SPORTDiscus, Web of Science and Scopus to May 2022 and pooled 35 RCTs covering 1,192 participants. Animal studies and disease-specific populations were excluded. The outcome was lean body mass. Subgroup analyses split results by age, sex and exercise type.

supplementation

In 45 young vegetarian adults, 5 g/day of creatine for 6 weeks improved both backward digit…

Caroline Rae and colleagues tested 45 young adult vegetarians in a double-blind, placebo-controlled, cross-over trial. The dose was 5 g/day of oral creatine monohydrate. The duration was six weeks per arm. Two outcomes were measured: working memory by backward digit span, and non-verbal intelligence by Raven's Advanced Progressive Matrices. Creatine improved both.

supplementation

Pooling 12 studies with 177 creatine and 263 control participants, creatine raised serum…

Elham Kabiri Naeini and colleagues searched PubMed, Scopus, Web of Science and Google Scholar for human studies published from January 2000 to March 2025. Twenty-one studies entered the systematic review. Twelve entered the serum-creatinine meta-analysis, covering 177 creatine-group and 263 control participants.

supplementation

In 8 pooled RCTs with 225 healthy participants, creatine improved memory performance with SMD…

Konstantinos Prokopidis and colleagues screened 7,277 unique publications and included 10 RCTs in the systematic review, 8 of which entered the meta-analysis. Those 8 trials covered 225 healthy participants: 122 on creatine, 118 on placebo, 74 male and 151 female. Doses ran from about 2.2 g/day to 20 g/day. Durations ran from 5 days to 24 weeks.

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In 58 adults with long COVID, nicotinamide riboside 2000 mg/day raised NAD+ within 5 weeks but…

Chao-Yi Wu and colleagues ran a single-centre, double-blind, placebo-controlled trial in Boston between August 2021 and September 2023. Fifty-eight community-dwelling adults with long COVID were randomised 2:1 after a placebo lead-in. Thirty-seven took nicotinamide riboside for 20 weeks. Twenty-one took placebo for 10 weeks and then nicotinamide riboside for 10 weeks.

supplementation

A triple-blind RCT in 97 children found combined omega-3 plus omega-9 lowered HOMA-IR and…

Ninety-seven children aged 8 to 17 with overweight or obesity and insulin resistance (HOMA-IR >3.0) were randomized to omega-3 (n=32), omega-9 (n=34), or combined omega-3 plus omega-9 (n=31) at 1.8 g/day for 3 months, followed by a 2-month follow-up. The primary outcome was change in HOMA-IR from baseline to end of treatment.

supplementation

A 12-week RCT in 90 adults found a multi-component nutraceutical containing berberine lowered…

Ninety adults with low-to-moderate cardiovascular risk and elevated LDL-C were randomized to NUT2 (n=45) or placebo (n=45) for 12 weeks, with both groups receiving standardized dietary advice. NUT2 is a proprietary multi-component nutraceutical; berberine appears among its components but the formulation was tested as a whole, not as isolated berberine.

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In 6,053 people, distinct HLA-II haplotypes were linked to Alzheimer disease risk, centenarian…

Daniel Alvarez Sirvent and colleagues fine-mapped seven independent HLA-II haplotypes in 6,053 people: 443 cognitively healthy centenarians, 3,219 population controls, and 2,391 people with Alzheimer disease. Three haplotypes overlapped prior Alzheimer disease or lifespan signals.

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Phase 3 (N=725) survodutide 3.6/6.0 mg weekly cut body weight ~12-13% vs 5.4% placebo at 76…

The SYNCHRONIZE-1 trial randomized 725 adults with obesity without diabetes 1:1:1 to weekly subcutaneous survodutide 3.6 mg, 6.0 mg, or placebo for 76 weeks. Survodutide is a dual GLP-1/glucagon receptor agonist from Boehringer Ingelheim, licensed from Zealand Pharma.

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L-taurine did not improve fatigue in decompensated cirrhosis; only a post hoc subgroup without…

Open-label RCT in 220 adults with decompensated cirrhosis and clinically significant fatigue, published in Hepatology Communications in 2026. Patients took 1000 mg/day L-taurine plus standard care or standard care alone for 12 weeks; 202 completed.

mechanism

Registered spermidine xerostomia trial NCT07035626 is still recruiting, N=58 estimated, no…

This is a registered trial only. Xingchen Peng at West China Hospital registered a spermidine trial for prevention of radiation-induced dry mouth in head and neck cancer patients. Enrollment 58, estimated. Study started 2025-06-25 and the registry status is still RECRUITING. No resultsSection exists on ClinicalTrials.gov.

supplementation

SmartAge: 12-month spermidine 0.9 mg/day did not improve memory in 100 older adults with…

SmartAge tested wheat-germ spermidine 0.9 mg/day versus microcrystalline cellulose in 100 adults (mean age 69) with subjective cognitive decline over 12 months. The primary endpoint was mnemonic discrimination on the Mnemonic Similarity Task. Between-group difference −0.03, 95% CI −0.11 to 0.05, P = 0.47. Secondary cognitive outcomes and hippocampal volume did not differ.

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Daily multivitamin improved global cognition 0.07 SD over 3 years in 2,262 older adults; cocoa…

COSMOS-Mind randomized 2,262 adults (mean age 73, 60% female) to cocoa extract, a daily multivitamin, both, or neither for three years. The multivitamin arm improved global cognition by 0.07 SD versus placebo (p=0.007). Memory and executive function composites also favored the multivitamin. The cocoa extract arm showed no benefit on global cognition (0.03 SD, p=0.28).

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In 127 Asian Indian adults with prediabetes, 24 weeks of metformin increased leukocyte…

Surya Prakash Bhatt, Shivam Pandey, and Anoop Misra randomized 127 North Indian adults aged 30 to 60 years with prediabetes to metformin 500 mg twice daily or placebo for 24 weeks. Both groups received lifestyle counseling. The trial was participant-blinded and outcome-assessor-blinded. Of 127 randomized participants, 112 completed the protocol.

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240 mg/day ginkgo over 6.1 years did not reduce dementia or Alzheimer's incidence in 3,069…

The Ginkgo Evaluation of Memory study randomized 3,069 community-dwelling adults aged 75+ with normal cognition or mild cognitive impairment to standardized ginkgo extract EGb 761 at 120 mg twice daily or placebo, median follow-up 6.1 years. Dementia incidence was not reduced: hazard ratio 1.12 (95% CI 0.94-1.33) - a point estimate in the wrong direction.

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N=80, 24 weeks: dulaglutide 0.75 mg weekly cut glycaemic variability (CV 39.45% to 35.05%)…

Open-label randomised trial in 80 adolescents aged 10-18 with transfusion-dependent beta-thalassaemia diabetes uncontrolled on metformin. Dulaglutide 0.75 mg subcutaneous weekly vs basal-bolus insulin for 24 weeks. Primary endpoint glucose coefficient of variation fell from 39.45% to 35.05% with dulaglutide (p<0.001) and rose from 39.85% to 43.26% with insulin (p<0.001).

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Ketogenic MCT drink 30 g/day improved recall, fluency, naming and trail-making in MCI over 6…

BENEFIC randomized adults with mild cognitive impairment to a ketogenic MCT drink (15 g twice daily) or placebo for six months; 39 and 44 participants were analyzed. Free and cued recall (p=0.047), category fluency (p=0.024), naming (p=0.033) and Trail-Making Test errors (p=0.017) all improved versus placebo.

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N=78: plasma LL-37 was 47.1 ng/L at AHI >= 15 vs 75.3 ng/L at AHI < 15 — a biomarker…

Observational study in 78 participants (58 obstructive sleep apnea patients, 20 healthy controls). Plasma LL-37 measured 75.3 +/- 29.3 ng/L in the AHI < 15 group vs 47.1 +/- 18.3 ng/L in the AHI >= 15 group — roughly 37% lower with more severe apnea.

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B vitamins slowed whole-brain atrophy from 1.08% to 0.76%/year in MCI; 53% slower when…

VITACOG randomized 271 adults aged 70+ with mild cognitive impairment to folic acid 0.8 mg, vitamin B12 0.5 mg and vitamin B6 20 mg daily, or placebo, for 24 months. In the MRI subset, annual whole-brain atrophy was 0.76% per year in the B-vitamin group versus 1.08% in placebo (95% CIs 0.63-0.90 and 0.94-1.22).

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Among healthy adults aged 65 or older, a self-selected vegan diet reduced protein intake and…

Jacintha Domić and colleagues randomized 72 healthy adults aged 65 years or older to a self-selected vegan diet, a habitual omnivorous diet, or a vegan diet combined with resistance exercise for 12 weeks. The study used MRI, DXA, deuterium oxide, and muscle-protein-synthesis measures.

supplementation

Omega-3 plus inositol matched N-acetylcysteine for mood symptoms in emotionally dysregulated…

Open-label randomized trial in youth aged 5-17 with emotional dysregulation, with and without autism traits. One arm took omega-3 fatty acids plus inositol: 1020 mg EPA plus 1000-2000 mg inositol daily. The other took N-acetylcysteine 1800-2700 mg daily. Duration was 6 weeks. Both groups improved modestly on mania and depression.

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Multi-author review of NAD+ supplementation trials: safety is consistent, bioavailability and…

Early findings from clinical trials of NAD+ precursors showed promise for slowing aging and fighting Alzheimer's disease, with some trials reporting improvements in memory, physical movement, and metabolic health. This is significant because Alzheimer's disease has no effective disease-modifying treatment, and NAD+ precursors (NMN, NR) are widely available as supplements.

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In 202 older adults, 12 weeks of self-directed bright daytime light was feasible and…

Débora B Constantino and colleagues recruited 202 adults aged 63 to 92 years in Amsterdam, Bologna, and Tartu. After a two-week baseline with wearables and diaries, participants were randomized to 12 weeks of self-implemented indoor light supplementation using a lamp above 8,000 melanopic EDI or to no intervention. A two-week reassessment followed.

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Across three cohorts, older-looking brain connectivity was linked to poorer cognition…

Kanhao Zhao and colleagues evaluated a functional-connectivity brain-aging index in three cohorts. The discovery cohort included 674 adults, the replication cohort 444, and an independent multi-omics cohort 344. The index was the age-bias-corrected difference between predicted and chronological brain age.

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LongevityBench found that compact aging-focused language models matched or exceeded larger…

Alex Zhavoronkov and colleagues introduced LongevityBench, an open benchmark with 17 tasks across five biodata domains, and tested 18 frontier AI systems from six developer teams. They also fine-tuned five aging-focused Longevity-LLMs ranging from 0.6 to 9 billion parameters. No single model dominated every task.

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Alpha-lipoic acid 1,800 mg/day plus letrozole raised ovulation per cycle from 71.9% to 92.2%…

Researchers at Menoufia University Hospitals randomized 151 infertile women with polycystic ovary syndrome 1:1 to letrozole alone (n=76) or letrozole plus alpha-lipoic acid 1,800 mg/day (n=75) for up to three cycles. Ovulation per cycle occurred in 92.2% of ALA cycles versus 71.9% of letrozole-only cycles (p=0.035). Mono-ovulation rate was 72.3% versus 60.1% (p=0.014).

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In 57 youth with migraine, 12 weeks of omega-3 raised blood EPA and DHA but did not improve…

Nutrients published a quasi-randomized, double-blind, placebo-controlled pilot from the University of North Carolina. Fifty-seven children and adolescents aged 10-17 with migraine received daily omega-3 (340 mg EPA + 510 mg DHA) or coconut oil placebo for 12 weeks; 44 completed.

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Severe periodontitis and tooth loss were associated with roughly 1 to 2 extra years on several…

Chen, Wang, Romandini and Michaud analysed 1,926 adults aged 50 years and older from the 1999–2002 National Health and Nutrition Examination Survey. They compared periodontal status and edentulism with four DNA-methylation clocks. Stage III or IV periodontitis was associated with 2.12 additional PhenoAge years, 1.48 Hannum years and 1.35 GrimAge2Mort years after adjustment.

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In 232 adults with type 2 diabetes, oral semaglutide lowered HbA1c and weight over 24 months…

Baldassarre and colleagues assessed oral semaglutide in routine care over 24 months in 232 adults with type 2 diabetes. Mean HbA1c fell by 0.8 percentage points and weight by 5.7 kg. Forty-four percent reached the combined target of HbA1c at or below 7% and at least 5% weight loss. Treatment persistence at 24 months was 68.5%.

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Resveratrol 500 mg/day for 180 days improved periodontal healing in 38 smokers; a dental…

Evidence-based Dentistry published a commentary on a double-blind, placebo-controlled trial by Lucchesi et al. (Clin Oral Invest 2025). Thirty-eight adult smokers with Stage III or IV, Grade C periodontitis received full-mouth ultrasonic debridement plus either systemic resveratrol 500 mg/day or placebo for 180 days, 19 per group. Follow-up ran 12 months.