Resveratrol

Authors:

Arrigo FG Cicero, Massimiliano Ruscica

Findings:

Preclinical models suggest resveratrol has neuroprotective effects via antioxidant, anti-inflammatory, and cell signaling pathways (e.g., SIRT1, AMPK). Human randomized clinical trials indicate resveratrol may improve cerebral blood flow, cerebral vasodilator responsiveness, some cognitive test performances (e.g., memory retention), perceived fatigue, and potentially slow the decline of Aβ40 levels in cerebrospinal fluid and plasma in specific populations, although cognitive effects were not consistently observed across all cited studies and dosages.

Participants:

Preclinical models: aged mice, rat models (AD-like pattern, vascular dementia, chronic mild stress, old rats, late middle-age rats), in vitro rat hippocampal H19-7 neuronal cells. Human studies cited involved: young healthy humans (N=60, aged 18-30), obese adults, overweight older adults, individuals with mild-to-moderate AD (N=119), type 2 diabetes adult patients, post-menopausal women, patients with mild cognitive impairment (MCI).

Dosage:

Preclinical models: 100 mg/kg (intraperitoneal injection, mice), 30 mg/kg/day (rats, 8 weeks), 20 mg/kg/day (rats, chronic), 75 μM (in vitro). Human trials cited used: single oral doses of 250 mg and 500 mg trans-resveratrol; 75 mg daily (6 weeks); 200 mg/day (with 320 mg quercetin, 26 weeks); dose escalation from 500 mg once daily to 1000 mg twice daily (52 weeks); single doses of 75 mg, 150 mg, or 300 mg. Dose-dependent increase in CBF noted; maximum improvement in cerebral vasodilator responsiveness observed with 75mg dose in one study.

Study Quality Assessment:

The text describes itself as a review aiming to critically review available evidence. It cites human evidence derived from randomized clinical trials (RCTs), including double-blind, placebo-controlled, crossover, and parallel-groups designs. Specific methods mentioned in cited studies include near-IR spectroscopy, magnetic resonance imaging (MRI), and transcranial Doppler ultrasound. Sample sizes (N=60, N=119) and study durations (28 days, 6 weeks, 14 weeks, 26 weeks, 52 weeks) are mentioned for some cited trials. Limitations acknowledged in the discussion include resveratrol's low oral bioavailability and the need for long-term RCTs with adequate dosages and improved bioavailability formulations.

All Effects:

Authors:

Stephen D Anton

Findings:

Supplementation with 1000 mg/day of resveratrol for 90 days selectively improved psychomotor speed (Trail Making Test part A) compared to 300 mg/day and placebo groups. No significant effects were observed in other cognitive domains tested (visual attention, working memory, verbal fluency, semantic memory). The findings offer modest support for further research.

Participants:

N = 32 sedentary, overweight older adults (age range: 65–93 years, M age = 73.34 years). Participants were healthy, community-dwelling, nonsmokers, with BMI 25–34.9 kg/m2, MMSE >24, and sedentary (<120 min moderate activity/week).

Dosage:

Participants randomized to placebo, 300 mg/day resveratrol, or 1000 mg/day resveratrol, taken as one capsule twice daily (morning and evening) for 90 days.

Study Quality Assessment:

Double-blind, Phase IIa randomized, placebo-controlled trial (N=32) over 90 days. Used intention-to-treat analysis and analysis of covariance. Cognitive function assessed with a test battery (Trail Making, Digits Forward/Backward, Erikson-Flanker, COWA, HVLT-R, Task Switching). Adherence measured by pill counts. Limitations acknowledged: small sample size, homogenous sample (race/ethnicity), short duration (90 days), limited generalizability (sedentary, overweight older adults), inability to rule out effects of other polyphenols in the product. Funding sources (NIH, foundations) and one author's conflict of interest (consultant for product provider) disclosed.

Authors:

Sonia L Ramírez-Garza

Findings:

Resveratrol (RV) bioavailability depends on dose, formulation, particle size, food matrix, repeated dosing, circadian variation, and gut microbiota. RV supplementation is generally safe up to 5g/day, though doses ≥2.5g may cause GI issues; excretion is rapid (mainly within 4 hours). RV shows potential for modulating neuroinflammation (e.g., in AD) and improving antioxidant capacity, but results are conflicting regarding benefits for Type 2 Diabetes, cardiovascular markers, endothelial function, and cognitive performance, likely due to variations in study design, dosage, and participant characteristics.

Participants:

Review covers trials involving healthy subjects, patients with Alzheimer's disease, Type 2 Diabetes, Friedreich ataxia, colorectal cancer, high cardiovascular risk, or undergoing peritoneal dialysis, as well as overweight/obese individuals (some with specific conditions like impaired glucose tolerance, NAFLD, borderline hypertension), and post-menopausal women.

Dosage:

Review covers trials using various doses, including single doses (e.g., 30mg, 40mg, 75mg, 250mg, 270mg, 400mg, 5g) and daily doses ranging from 75mg to 5g (e.g., 75mg/day, 80mg/day, 150mg/day, 450mg/day, 1g/day, 1-2g/day, 2.5g/day, 3g/day, 5g/day). Some studies used escalating doses (e.g., 500mg/day up to 1000mg twice daily) or multiple doses per day (e.g., 25-150mg six times/day, 2000mg twice daily). Co-administration with piperine (20mg) or EGCG (282mg/day) was also studied. Micronized RV (SRT501) was tested at 5g/day.

Study Quality Assessment:

The review summarizes results from human clinical trials conducted in the last decade. Specific trials mentioned include designs like Phase I, Phase II, randomized, double-blind, placebo-controlled, crossover, open-label, single-dose, multiple-dose, parallel-group, and controlled intervention studies. Sample sizes (n) are listed for individual studies in tables. Some studies are noted as 'rated class II because more than two primary outcomes were designated'. Potential confounding factors like dose, administration medium, participant health status, gut microbiota, age, gender, lifestyle, and interactions with medications (e.g., metformin) are mentioned as reasons for contrasting results. Funding sources and conflicts of interest for the review authors are declared.

All Effects:

Authors:

McDermott M.P.

Findings:

Meta-analysis indicated that postmenopausal women performed significantly worse than pre- and perimenopausal women on delayed verbal memory tasks, and significantly worse than perimenopausal women on phonemic verbal fluency tasks, although effect sizes were small. Both peri- and postmenopausal women showed a significantly increased risk (odds ratios ranging from 1.3 to 4.3 depending on stage and measure) of depressive symptoms (measured by CES-D ≥ 16) and diagnosis of Major Depression (measured by structured clinical interviews) compared to premenopausal women.

Participants:

Review of observational studies involving premenopausal, perimenopausal, and postmenopausal women (midlife women). Exclusion criteria included surgical menopause and special populations (e.g., breast cancer, psychiatric disorders). Included studies involved women with mean ages ranging from approximately 40 to 52 years and varied in racial/ethnic composition.

Study Quality Assessment:

Systematic review and meta-analysis following PRISMA guidelines. Searched PubMed for observational studies (cross-sectional for cognition, longitudinal for mood) using specific MeSH terms and inclusion/exclusion criteria. Data extraction independently conducted by two reviewers. Fixed effects models used for meta-analysis to estimate overall standardized effect sizes (SES) for cognition and log odds ratios for depression. Some included studies adjusted for covariates (e.g., age, education, race, site, health status, mood symptoms), but adjustments varied. Limitations acknowledged include the small number of studies included (four for cognition, four for mood), potential lack of generalizability beyond included studies, differences in menopausal staging criteria and data reporting across studies, and inability to use random effects models.

All Effects:

Findings:

Out of ten included studies, three found significant improvements in some cognitive measures with resveratrol, two had mixed findings, and five found no effect. Meta-analysis showed significant effects on delayed recognition (SMD, 0.39) and negative mood (SMD, -0.18). Conclusions suggest resveratrol might improve select cognitive measures, but the literature is inconsistent and limited.

Participants:

Adults (healthy and clinical populations). Specific analyses included n=166 and n=163 participants.

Study Quality Assessment:

Systematic literature review and meta-analysis of randomized controlled trials. Used Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Assessed risk of bias using the Cochrane Collaboration Risk of Bias tool. Assessed quality of evidence using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). Included studies generally had low risk of bias and were of moderate or high quality. Pooled analyses based on n=3 studies (n=166 participants) for delayed recognition and n=3 studies (n=163 participants) for negative mood.

All Effects: