Disinfection by-products in drinking water and risk of colorectal cancer: a population-based cohort study

High levels of trihalomethanes in drinking water may increase the risk of proximal colon cancer in men.

Is there an association between long-term exposure to trihalomethanes (THMs) in drinking water and the incidence of colorectal cancer in humans?

Hypothesis: The study implicitly hypothesizes that long-term exposure to THMs, known rodent carcinogens, may be associated with an increased risk of colorectal cancer in humans, despite inconclusive prior evidence.

This population-based cohort study assessed the association of long-term THM exposure with colorectal cancer incidence in 58,672 men and women from two cohorts. Exposure was determined by combining residential history with drinking water-monitoring data, categorizing participants into no exposure, low exposure (<15 µg/L), and high exposure (≥15 µg/L). Incident colorectal cancer cases were identified using the Swedish National Cancer Register.

Over an average follow-up of 16.8 years (988,144 person-years), 1913 colorectal cancer cases were identified. High THM concentrations (≥15 µg/L) were associated with an increased risk of colorectal cancer in men (hazard ratio = 1.26). This association was statistically significant for proximal colon cancer in men (hazard ratio = 1.59) but not for distal colon or rectal cancer. No overall association was observed in women.

The results suggest that disinfection by-products, specifically THMs in drinking water, may be a possible risk factor for proximal colon cancer in men, even at concentrations lower than those in most previous studies.

The abstract does not explicitly state limitations of the study, but it notes that evidence in humans for carcinogenicity associated with disinfection by-products is still inconclusive, implying the need for further research.


Assessment of drinking water safety in the Netherlands using nationwide exposure and mortality data

Higher magnesium in drinking water was linked to lower coronary heart disease mortality, while higher calcium and water hardness were linked to increased cardiovascular disease mortality.

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

Are there associations between drinking water quality parameters (nitrate, water hardness, calcium, magnesium) and mortality from cardiovascular diseases (including coronary heart disease) and colorectal cancer in the Netherlands?

Hypothesis: The study aims to explore associations, suggesting an underlying hypothesis that such associations might exist, given public concern about long-term intake health risks.

A cohort of 6,998,623 Dutch residents aged 30 or older, living at the same address for at least five years as of January 1, 2008, was created using national administrative databases. Drinking water concentrations from 2000-2010 were used as exposure indicators. Age-stratified Cox proportional hazards models were applied to analyze associations between water quality parameters and cause-specific mortality.

A 10 mg/L increase in magnesium was associated with a reduced risk for coronary heart disease mortality (HR: 0.95, 95% CI: 0.90, 0.99). A 100 mg/L increase in calcium was associated with an increased risk for cardiovascular disease mortality (HR: 1.08, 95% CI: 1.03, 1.13). A 2.5 mmol/L increase in water hardness was associated with an increased risk for cardiovascular disease mortality (HR: 1.06, 95% CI: 1.01, 1.10). An elevated risk for coronary heart disease mortality was observed at calcium concentrations below 30 mg/L, but no overall exposure-response relation was found for calcium. No other statistically significant associations were found for other combinations of water quality parameters and causes of death.

This explorative study identified a protective effect of magnesium against coronary heart disease mortality and an increased risk of cardiovascular disease mortality associated with calcium concentration and water hardness in drinking water.

The study is explorative, and while it identified associations, it did not establish causality. The abstract does not explicitly state other limitations.


High Content of Lead Is Associated with the Softness of Drinking Water and Raised Cardiovascular Morbidity

This review aims to assess the link between lead in drinking water, especially soft water, and cardiovascular disease.

Does lead content in drinking water, particularly soft water, correlate with increased cardiovascular morbidity in human populations?

Hypothesis: Low levels of magnesium and calcium (soft water) may increase lead leaching from pipes and enhance lead absorption, thereby increasing the risk of cardiovascular pathologies.

This study is a review that evaluates existing evidence for an association between lead exposure from drinking water and cardiovascular endpoints in human populations.

The abstract does not present new numerical results or specific findings from the review itself, but rather states the purpose of the review.

The abstract does not provide a conclusion as it describes the intent of the review rather than its findings.

The abstract does not explicitly state limitations of the review, but as a review, its findings are dependent on the quality and availability of the existing literature.


Earthing: health implications of reconnecting the human body to the Earth's surface electrons

Connecting with the Earth's electrons through earthing may improve sleep and reduce pain.

What are the health implications of reconnecting the human body to the Earth's surface electrons?

Hypothesis: The hypothesis is that direct physical contact with the Earth's surface electrons, a practice known as earthing or grounding, may promote physiological changes and improve well-being, and that the modern disconnect from this contact may contribute to physiological dysfunction and unwellness.

This paper is a review of existing earthing research. It synthesizes findings from various studies on the effects of direct physical contact with the Earth's surface electrons on human health.

Emerging scientific research suggests that direct physical contact with the Earth's electrons promotes physiological changes and subjective reports of well-being. Specific benefits mentioned include better sleep and reduced pain.

Reconnecting with the Earth's electrons through earthing (grounding) appears to be a simple, easily accessible, and potentially clinically significant modality for improving health, including better sleep and reduced pain.

The abstract does not explicitly state limitations of the reviewed research. It primarily focuses on presenting the positive findings and potential of earthing.


Susceptibility of an Airborne Common Cold Virus to Relative Humidity

The survival of airborne common cold virus (HRV-16) is significantly higher when aerosols are in a solid, effloresced state or within a specific humidity range, compared to a liquid, deliquesced state.

How does relative humidity (RH) affect the viability of airborne human rhinovirus-16 (HRV-16), and what mechanism underlies this dependence?

Hypothesis: The 'efflorescence/deliquescence divergent infectivity' (EDDI) model accurately predicts the RH-dependent survival of airborne human rhinovirus-16 (HRV-16).

The efflorescence and deliquescence RH of aerosols nebulized from a protein-enriched saline carrier fluid, simulating human respiratory fluid, were measured. The RH range of the aerosols' hygroscopic hysteresis zone was found to be 38-68%. Carrier fluid containing HRV-16 was nebulized into sub-hysteresis (effloresced/solid) or super-hysteresis (deliquesced/liquid) zone air before transitioning the RH into the intermediate hysteresis zone. Surviving fractions (SFs) of the virus were measured 15 minutes post nebulization. SFs were also measured for aerosols introduced directly into the sub-hysteresis, super-hysteresis, and hysteresis zones without transition.

For transitioned aerosols in the hysteresis zone, SFs were higher for effloresced aerosols (0.17 ± 0.02) than for deliquesced aerosols (0.005 ± 0.005). For non-transitioned aerosols, SFs were 0.18 ± 0.06 in the sub-hysteresis zone, 0.05 ± 0.02 in the super-hysteresis zone, and 0.20 ± 0.05 in the hysteresis zone, showing a V-shaped SF/RH dependence.

The EDDI model's prediction of enhanced survival in the hysteresis zone for effloresced carrier aerosols was confirmed. The viability of airborne HRV-16 is significantly influenced by the effloresced or deliquesced state of the aerosol, with higher survival observed when aerosols are in an effloresced state or within the hysteresis zone.

The study used a simulated human respiratory fluid and measured survival at a single time point (15 minutes post nebulization).


Blue-Light Therapy for Seasonal and Non-Seasonal Depression: A Systematic Review and Meta-Analysis

Blue-light therapy's effectiveness for seasonal and non-seasonal depression remains unproven based on current evidence.

Does blue-light therapy effectively and safely treat seasonal and non-seasonal major depressive disorder (MDD) compared to active and inactive control conditions?

Hypothesis: The study aimed to determine the efficacy and safety of blue-light therapy for seasonal and non-seasonal MDD.

A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted by searching Web of Science, EMBASE, Medline, PsycInfo, and Clinicaltrials.gov. Data was extracted by two independent reviewers. The primary outcome was the difference in endpoint scores on the SIGH-SAD or SIGH-ADS, while secondary outcomes included response (≥ 50% improvement) and remission rates.

Nine RCTs (347 participants) were included, with seven focusing on seasonal MDD and two on non-seasonal MDD. A meta-analysis found no evidence for blue-light efficacy compared to inactive conditions (mean difference = 2.43; 95% CI, -1.28 to 6.14) and no differences compared to active conditions (mean difference = -0.11; 95% CI, -2.38 to 2.16). There were also no significant differences in response and remission rates. Blue-light therapy was generally well-tolerated.

The efficacy of blue-light therapy for treating seasonal and non-seasonal MDD is not yet proven.

Future trials need to be of longer duration, include larger sample sizes, and standardize light therapy parameters more effectively.


Efficacy of light therapy versus antidepressant drugs in major depressive episodes: a meta-analysis

Combining light therapy with antidepressants is more effective than antidepressants alone for major depressive episodes, and light therapy alone is comparable to antidepressants alone.

no-difference-cue: "no significant difference" | favorable-cue: "effective"

This meta-analysis examines the efficacy of light therapy (LT) compared to antidepressant drugs (AD) and their combination (LT + AD) in treating major depressive episodes.

Hypothesis: The study aims to determine if light therapy, alone or in combination with antidepressants, is as effective or more effective than antidepressant drugs alone for major depressive episodes.

A systematic review and weighted random effect meta-analysis was conducted on randomized controlled trials directly comparing light therapy and antidepressant drugs, as well as their combination. Seven independent populations, totaling 397 participants with moderate to severe major depressive episodes, were included. The median intervention duration was 5 weeks.

The superiority of LT + Placebo compared to AD + Placebo was not statistically significant (SMD = 0.19; p = 0.17). However, the combination of LT + AD was superior to AD + Placebo (SMD = 0.56; p < 0.001). This superiority was also observed in patients with non-seasonal depression (SMD = 0.55; p = 0.005). Heterogeneity between studies was low (I = 0%, 18.41%, and 39.23%), and no publication biases were found.

No significant difference was observed between light therapy alone and antidepressant drugs alone. The combination of light therapy and antidepressant drugs showed clear superiority. Therefore, both light therapy monotherapy and the combination therapy may be considered first-line treatments for seasonal and non-seasonal depression.

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


Comparative efficacy and safety of tranexamic acid for melasma by different administration methods: a network meta-analysis

Oral tranexamic acid combined with routine topical agents is the most effective treatment for melasma, with oral TA alone showing faster short-term effects.

What are the comparative efficacy and safety of different administration methods of tranexamic acid (TA) for treating melasma?

Hypothesis: The study aims to compare the efficacy and safety of various TA administration methods for melasma.

A network meta-analysis was conducted by collecting research from PubMed, EMBASE, Cochrane Library, and Web of Science. The severity of melasma was evaluated using the Melasma Area Severity Index (MASI), and the curative effect was assessed by comparing the change in MASI (ΔMASI) after treatment with different TA administration methods at specific time points.

At Weeks 4, 8, 12, and the last follow-up, oral TA combined with routine topical agents (oTA + RTA) showed a higher ΔMASI than intradermal TA (iTA), topical TA (tTA), and microneedling TA (MNsTA), with statistical significance. At Week 8, oral TA (oTA) had a statistically significantly higher ΔMASI than iTA. Compared to placebo, oTA showed statistically significant differences at Week 4, while tTA, iTA, and MNsTA showed statistically significant differences starting from Week 8.

Among the various TA administration methods, oTA + RTA has the best effect on melasma. In the short term, oTA's curative effect is better than iTA's, and its onset time is faster than tTA, iTA, and MNsTA. In the long run, the curative effect of TA alone is independent of the administration mode.


Effectiveness of laser and topical tranexamic acid combination therapy in melasma: a meta-analysis

Combining laser therapy with topical tranexamic acid is an effective treatment for melasma, with fractional CO2 laser and daily TXA showing the best results.

Does the topical application of tranexamic acid (TXA) increase the efficacy of laser therapy in treating melasma?

Hypothesis: The combination of laser therapy and topical tranexamic acid will be more effective in treating melasma compared to laser therapy alone.

A meta-analysis was conducted by systematically searching PubMed/MEDLINE, Cochrane Central, Google Scholar, Scopus, and the International Clinical Trials registry. Two independent reviewers screened articles using the Covidance database per PRISMA guidelines. Clinical improvement was measured using the Melasma Area of Severity Index (MASI) or modified MASI (mMASI). Nine studies describing the combined use of topical tranexamic acid with various laser therapies were included.

The combination of laser therapy and topical TXA significantly decreased the MASI score (P < 0.0001). Subgroup analyses indicated that fractional CO2 laser was the most effective laser type, and a regimen of monthly laser plus twice daily topical TXA was most effective in decreasing MASI/mMASI scores.

Combining topical tranexamic acid and laser therapy is an effective and safer treatment option for treatment-resistant melasma. Specifically, monthly fractional CO2 laser combined with daily topical tranexamic acid showed high effectiveness and safety.

The abstract does not explicitly state any limitations of the meta-analysis itself, such as heterogeneity among studies or publication bias.


WHO Environmental Noise Guidelines: Environmental Noise and Cardiovascular and Metabolic Effects: A Summary

Exposure to road traffic noise is associated with an increased risk of ischemic heart disease.

What are the effects of environmental noise exposure on the cardio-metabolic systems?

Hypothesis: The study aimed to update the current state of evidence and assess its quality regarding the effects of environmental noise exposure on cardio-metabolic systems.

A systematic review was conducted, identifying 600 references published between January 2000 and August 2015 on noise from road, rail, air traffic, and wind turbines. Sixty-one studies with exposure-response information were used for meta-analyses and quality assessment using GRADE. The most comprehensive evidence was available for road traffic noise and Ischemic Heart Diseases (IHD), combining results from 7 longitudinal studies.

Combining 7 longitudinal studies, a Relative Risk (RR) of 1.08 (95% CI: 1.01-1.15) per 10 dB (L) was found for the association between road traffic noise and the incidence of IHD. The quality of this evidence was rated as high. Evidence for other associations like transportation noise with stroke, diabetes, and obesity was limited, with quality rated from moderate to very low.

There is high-quality evidence linking road traffic noise to an increased risk of Ischemic Heart Disease. More and higher quality longitudinal studies are needed for a comprehensive assessment of noise exposure's impact on the cardiovascular and metabolic system, especially for outcomes like stroke, diabetes, and obesity.

Many studies on traffic noise and hypertension were cross-sectional and had a high risk of bias. Only a few studies reported on associations between transportation noise and stroke, diabetes, and/or obesity, and the quality of evidence for these was rated from moderate to very low.


Long-term exposure to traffic noise and mortality: a systematic review and meta-analysis

Long-term road traffic noise may be weakly associated with ischemic heart disease mortality, but evidence for other mortality outcomes and traffic noise sources is generally weak.

Does long-term exposure to road, rail, and aircraft traffic noise affect non-accidental and cardiovascular mortality?

Hypothesis: The study aimed to update the evidence base regarding the association between long-term traffic noise exposure and mortality outcomes.

A systematic review and meta-analysis were conducted following PRISMA guidelines, searching PubMed, Scopus, Web of Science, and EMBASE for literature published between January 1, 2000, and October 5, 2020. Thirteen studies were selected, and risk estimates were converted to per 10 dB higher L for each traffic source. Inverse-Variance heterogeneity (I-Vhet) meta-analysis was used to pool risk estimates, with sensitivity and subgroup analyses performed.

For road traffic noise, the pooled relative risk (RR) per 10 dB higher L for non-accidental mortality was 1.01 (95% CI: 0.98, 1.05), for CVD mortality was 1.01 (95% CI: 0.98, 1.05), for ischemic heart disease (IHD) mortality was 1.03 (95% CI: 0.99, 1.08), and for stroke mortality was 1.05 (95% CI: 0.97, 1.14). A possible threshold of 53 dB was visually suggested for CVD-related mortality from road traffic noise. Pooled estimates for aircraft noise were based on fewer studies and varied by outcome.

Evidence for long-term exposure to traffic noise on mortality remains weak, with the exception of the association between road traffic noise and IHD mortality. The overall quality of evidence was generally very low to low, except for CVD or IHD mortality, which was rated as moderate.

The overall quality of evidence for most meta-analyses was rated as very low to low. Pooled estimates for aircraft noise were based on fewer studies.


Effects of taurine supplementation following eccentric exercise in young adults

Taurine supplementation may help reduce muscle damage and oxidative stress and improve strength after eccentric exercise, but it does not affect inflammation.

no-difference-cue: "does not affect" | favorable-cue: "improve"

What are the effects of taurine supplementation on muscle performance, oxidative stress, and inflammation after eccentric exercise in young adult males?

Hypothesis: The study hypothesized that taurine supplementation would affect muscle performance, oxidative stress, and inflammation response after eccentric exercise.

Twenty-one male participants were randomly assigned to either a placebo (n=10) or taurine (n=11) group. After 14 days of supplementation, subjects performed eccentric exercise of the elbow flexors. Blood samples and muscle performance measurements were taken on days 1, 14, 16, 18, and 21 to analyze performance, muscle damage, oxidative stress, and inflammatory markers.

Taurine supplementation increased strength levels and thiol total content, while decreasing muscle soreness, lactate dehydrogenase, creatine kinase activity, and oxidative damage (xylenol and protein carbonyl). However, antioxidant enzymes (superoxide dismutase, catalase, gluthatione peroxidase) and inflammatory markers (tumor necrosis factor, IL-1β, and IL-10) were not altered compared to the placebo group.

Taurine supplementation may improve performance and reduce muscle damage and oxidative stress after eccentric exercise, but it does not appear to decrease the inflammatory response.

The abstract does not explicitly state limitations of the study.


L-carnitine in the secondary prevention of cardiovascular disease: systematic review and meta-analysis

L-carnitine may reduce mortality, ventricular arrhythmias, and angina after a heart attack, but more research is needed.

favorable-cue: "reduction in all-cause mortality"

What are the effects of L-carnitine compared with placebo or control on morbidity and mortality in patients who have experienced an acute myocardial infarction?

Hypothesis: The study implicitly hypothesizes that L-carnitine may reduce morbidity and mortality outcomes following an acute myocardial infarction.

A systematic review and meta-analysis of 13 controlled trials (N=3629) was conducted. The trials compared L-carnitine to placebo or control and were identified through searches of Ovid MEDLINE, PubMed, and Embase databases. Outcomes assessed included mortality, ventricular arrhythmias (VAs), angina, heart failure, and reinfarction.

L-carnitine was associated with a 27% reduction in all-cause mortality, a 65% reduction in ventricular arrhythmias, and a 40% reduction in the development of angina. There was no significant reduction in the development of heart failure or myocardial reinfarction.

L-carnitine is associated with a reduction in all-cause mortality, ventricular arrhythmias, and anginal symptoms in patients who have experienced an acute myocardial infarction.

The abstract does not explicitly state limitations of the meta-analysis itself, but it does suggest that further large randomized controlled trials are warranted.


Examining oxidative stress as a mechanistic link between sleep irregularity and cardiovascular risk

Oxidative stress links irregular sleep and increased cardiovascular risk in young adults with chronic anxiety, and antioxidants may help improve blood pressure control.

unfavorable-cue: "increased cardiovascular risk" | favorable-cue: "improve"

Does oxidative stress mediate the link between sleep irregularity and impaired vascular function and blood pressure control in young adults with chronic anxiety?

Hypothesis: The study hypothesized that impairments in vascular function and blood pressure control associated with sleep irregularity in young adults with chronic anxiety are driven by elevations in oxidative stress.

Twenty-five young adults (24 ± 4 yr) with generalized anxiety disorder (GAD) or elevated GAD symptoms were divided into high and low total sleep time irregularity (TSTI) groups based on wrist-worn accelerometry. Oxidative stress (whole blood superoxide levels), vascular function (exercise-induced flow-mediated dilation), and blood pressure control (cardiovagal baroreflex sensitivity) were measured in both groups after acute supplementation with either antioxidants (alpha-lipoic acid, vitamin C, and vitamin E) or a placebo.

The high TSTI group showed significantly greater oxidative stress, lower vascular function, and lower blood pressure control. Antioxidant supplementation significantly improved oxidative stress and blood pressure control in the high TSTI group. Vascular function improved significantly with antioxidant supplementation, independent of the group.

Oxidative stress is a key mechanism linking sleep irregularity and cardiovascular disease risk in young adults with chronic anxiety. Antioxidant supplementation reduced oxidative stress and normalized blood pressure control differences between groups, suggesting its role as a mediator.


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

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

Regular glucosamine use is associated with a lower risk of death from all causes and specific diseases like cancer, CVD, respiratory, and digestive diseases.

What are the associations between regular glucosamine use and all-cause and cause-specific mortality?

Hypothesis: The study aimed to evaluate the associations of regular glucosamine use with all-cause and cause-specific mortality.

This population-based prospective cohort study included 495,077 participants from the UK Biobank, recruited from 2006 to 2010 and followed through 2018. Researchers calculated hazard ratios (HRs) and 95% CIs for all-cause and cause-specific mortality using Cox proportional hazards models, adjusting for potential confounding variables.

During a median follow-up of 8.9 years, 19,882 all-cause deaths were recorded. Regular glucosamine use was associated with lower all-cause mortality (HR 0.85), CVD mortality (HR 0.82), cancer mortality (HR 0.94), respiratory mortality (HR 0.73), and digestive mortality (HR 0.74). The inverse association with all-cause mortality appeared stronger in current smokers.

Regular glucosamine supplementation was associated with lower mortality from all causes, cancer, cardiovascular disease, respiratory disease, and digestive diseases.


Genetically predicted glucosamine and longevity: A Mendelian randomization study

Genetically predicted higher glucosamine levels are associated with increased lifespan, particularly for mothers.

unfavorable-cue: "associated with increased"

What is the effect of genetically predicted glucosamine on male and female lifespan?

Hypothesis: The study hypothesized that genetically predicted glucosamine would be associated with longevity.

A two-sample Mendelian randomization (MR) study was conducted using genetic data from the MRC-IEU consortium for 461,384 individuals. Five genetic variants were identified as instrumental variables for genetically predicted glucosamine. Genetic associations of these variants with parental longevity (combined parental age at death, mother's age at death, father's age at death) were obtained. The inverse-variance weighted method was used to estimate the effect of a 1-standard deviation (SD) increase in genetically predicted glucosamine on parental longevity.

A 1-SD increase in genetically predicted glucosamine was associated with higher odds of combined parental age at death (odds ratio, 2.64) and maternal age at death (odds ratio, 1.73). No association was found with paternal age at death (odds ratio, 1.32). Sensitivity analyses did not find evidence of pleiotropic effects.

Lifelong higher levels of glucosamine may increase life expectancy, with positive effects specifically associated with maternal age at death. The sex-specific findings require further investigation.

The abstract does not explicitly state limitations beyond suggesting further investigation for the sex-specific finding.


Glucosamine/Chondroitin and Mortality in a US NHANES Cohort

Regular use of glucosamine/chondroitin supplements is associated with a lower risk of death from all causes and cardiovascular disease in US adults.

Does regular consumption of glucosamine/chondroitin affect overall and cardiovascular (CVD) mortality in US adults?

Hypothesis: Previous studies suggest an association between glucosamine/chondroitin intake and mortality, leading to the hypothesis that regular consumption may be linked to lower mortality rates in a national US sample.

This study analyzed combined data from 16,686 participants in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2010, linked with the 2015 Public-use Linked Mortality File. Cox proportional hazards models were used to assess the association between glucosamine/chondroitin use and all-cause and CVD mortality.

During a median follow-up of 107 months, there were 3366 total deaths (20.17%), with 674 (20.02%) attributed to CVD. Participants taking glucosamine/chondroitin for a year or longer (3.94% of the sample) showed a 39% reduction in all-cause mortality (HR = 0.61) and a 65% reduction in CVD mortality (HR = 0.35) after adjusting for age. After further adjustment for age, sex, race, education, smoking status, and physical activity, the association remained significant, with a 27% reduction in all-cause mortality (HR = 0.73) and a 58% reduction in CVD mortality (HR = 0.42).

Regular intake of glucosamine/chondroitin is associated with lower all-cause and CVD mortality in a national US cohort. These findings are consistent with previous studies in other populations.

The study design was observational, which means it cannot establish a causal link between glucosamine/chondroitin intake and reduced mortality. Prospective studies are needed to confirm these findings.


Glycine and N-Acetylcysteine (GlyNAC) supplementation in older adults improves glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, physical function, and aging hallmarks: A randomized clinical trial

GlyNAC supplementation in older adults can reverse several age-related health declines, including oxidative stress and mitochondrial dysfunction.

unfavorable-cue: "impaired" | favorable-cue: "improves"

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

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

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

Compared to young adults, older adults exhibited glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, insulin resistance, multiple aging hallmarks, and impaired physical function. GlyNAC supplementation in older adults for 16 weeks improved or corrected these defects, while the placebo did not. GlyNAC was safe and well-tolerated.

GlyNAC supplementation in older adults is an effective nutritional supplement that improves and reverses multiple age-associated abnormalities, including glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, insulin resistance, and impaired physical function, thereby promoting health in aging humans.


GlyNAC supplementation in mice increases length of life by correcting glutathione deficiency, oxidative stress, mitochondrial dysfunction, abnormalities in mitophagy and nutrient sensing, and genomic damage

GlyNAC supplementation extended the lifespan of mice by 24% and corrected several age-related cellular defects.

Can GlyNAC supplementation increase lifespan and improve age-associated defects in mice?

Hypothesis: GlyNAC supplementation will increase longevity by correcting glutathione deficiency, oxidative stress, and mitochondrial dysfunction.

The study evaluated the effect of GlyNAC supplementation versus a placebo in C57BL/6J mice. Researchers measured the length of life and assessed age-associated glutathione deficiency, oxidative stress, mitochondrial dysfunction, abnormal mitophagy, nutrient-sensing, and genomic damage in the heart, liver, and kidneys.

Mice supplemented with GlyNAC lived 24% longer than control mice. GlyNAC supplementation also improved or corrected impaired glutathione synthesis, glutathione deficiency, oxidative stress, mitochondrial dysfunction, abnormal mitophagy, nutrient-sensing, and genomic damage.

GlyNAC supplementation can increase lifespan and improve multiple age-associated defects in mice, providing a proof-of-concept for its potential as a nutritional supplement to enhance lifespan and healthspan.

This study was conducted in mice, and the findings may not directly translate to humans. Further investigation is warranted.


Higher spermidine intake is linked to lower mortality: a prospective population-based study

The American Journal of Clinical Nutrition

Higher dietary intake of spermidine is associated with a lower risk of all-cause mortality in humans.

unfavorable-cue: "associated with increased" | favorable-cue: "associated with a lower"

Is there an association between dietary spermidine intake and mortality in humans?

Hypothesis: Spermidine administration is linked to increased survival in several animal models, suggesting a potential association between dietary spermidine content and mortality in humans.

This prospective community-based cohort study included 829 participants aged 45-84 years, with diet assessed by repeated dietitian-administered food-frequency questionnaires in 1995, 2000, 2005, and 2010. All-cause mortality was tracked between 1995 and 2015, during which 341 deaths occurred. The association was also independently validated in the Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk (SAPHIR) Study.

All-cause mortality (deaths per 1000 person-years) decreased across thirds of increasing spermidine intake from 40.5 to 23.7 and 15.1. The age-, sex-, and caloric intake-adjusted 20-year cumulative mortality incidence was 0.48, 0.41, and 0.38 for the lowest, middle, and highest thirds of spermidine intake, respectively. The age-, sex-, and caloric ratio-adjusted HR for all-cause death per 1-SD higher spermidine intake was 0.74, and 0.76 after further adjustments. The difference in mortality risk between the top and bottom third of spermidine intakes was similar to that associated with a 5.7-year younger age.

Higher spermidine intake is linked to lower all-cause mortality in humans, providing epidemiologic support for the concept that spermidine-rich nutrition is associated with increased survival.

The study design is observational, which means it can show correlation but not causation. While adjustments were made for various factors, unmeasured confounding cannot be entirely ruled out.


Towards personalized NMN supplementation: nicotinamide adenine dinucleotide (NAD) concentration

NMN supplementation increases NAD levels and may improve physical function and quality of life, but individual responses vary greatly, suggesting personalized dosing is beneficial.

What is the optimal dose of NMN supplementation to improve blood NAD concentration and related health markers in adults aged 40-65?

Hypothesis: NMN supplementation will increase blood NAD concentration in a dose-dependent manner, and this increase will be associated with improvements in health markers.

This was a post-hoc analysis of a double-blinded clinical trial with 80 healthy adults aged 40-65. Participants received a placebo or daily doses of 300 mg, 600 mg, or 900 mg NMN for 60 days. Blood NAD concentration, blood biological age, HOMA-IR, 6-minute walk test, and SF-36 survey were measured at baseline and after supplementation.

NMN supplementation resulted in a significant dose-dependent increase in NAD concentration, with a large coefficient of variation (29.2-113.3%) within groups. The increase in NAD was associated with improvements in the 6-minute walk test distance and the SF-36 score. The median effective dose of NAD for the 6-minute walk test was 15.7 nmol/L and for the SF-36 score was 13.5 nmol/L.

NMN supplementation increases NAD concentration in a dose-dependent manner, which is associated with improved walking distance and quality of life. Due to high interindividual variability, monitoring NAD concentration is important for personalized NMN dosing.

The study noted a high interindividual variability in NAD concentration changes after NMN supplementation, indicating that a single optimal dose may not apply to everyone.


Potential Modulation of Inflammation by Probiotic and Omega-3 Supplementation in Elderly with Chronic Low-Grade Inflammation: A Randomized, Placebo-Controlled Trial

A combined probiotic and omega-3 supplement increased anti-inflammatory markers in elderly individuals, but did not significantly reduce hs-CRP.

no-difference-cue: "did not significantly reduce"

Can a combined probiotic and omega-3 supplement reduce low-grade inflammation in elderly individuals?

Hypothesis: The novel combination of a multi-strain probiotic and omega-3 supplements will reduce low-grade inflammation, as measured by high-sensitivity C-reactive protein (hs-CRP), in elderly participants.

This was a proof-of-concept, randomized, placebo-controlled, parallel study involving 76 community-dwelling elderly participants (median age 71.0 years). Participants received either the dual supplement (n=37) or a placebo (n=39) for eight weeks. Hs-CRP, cytokine levels, and intestinal permeability were assessed at baseline and after the intervention.

No significant difference was observed for hs-CRP between the dual supplement group and placebo. However, supplementation led to significant increases in the anti-inflammatory marker IL-10 and increased levels of valeric acid.

Probiotic and omega-3 dual supplementation exerts modest effects on inflammation, as evidenced by increased IL-10 and valeric acid, and may have potential as a non-pharmacological treatment for low-grade inflammation in the elderly.

The study did not find a significant reduction in the primary outcome measure, hs-CRP, suggesting the effects on inflammation might be modest or require different markers.


Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study

Pasteurized Akkermansia muciniphila supplementation is safe and may improve insulin sensitivity, cholesterol, and other metabolic markers in overweight/obese insulin-resistant individuals.

Can daily oral supplementation with Akkermansia muciniphila improve metabolic parameters in overweight/obese insulin-resistant human volunteers?

Hypothesis: Supplementation with A. muciniphila will be safe, well-tolerated, and improve metabolic parameters in overweight/obese insulin-resistant individuals, given its negative correlation with obesity-related disorders in previous studies.

This was a randomized, double-blind, placebo-controlled pilot study. 40 overweight/obese insulin-resistant volunteers were enrolled, with 32 completing the trial. Participants received daily oral supplementation of 10^10 A. muciniphila bacteria (either live or pasteurized) or a placebo for three months. Primary endpoints included safety, tolerability, and metabolic parameters (insulin resistance, circulating lipids, visceral adiposity, body mass), while secondary outcomes were gut barrier function (plasma lipopolysaccharides) and gut microbiota composition.

Daily oral supplementation of 10^10 A. muciniphila (live or pasteurized) for three months was safe and well tolerated. Compared to placebo, pasteurized A. muciniphila improved insulin sensitivity by 28.62%, reduced insulinemia by 34.08%, and decreased plasma total cholesterol by 8.68%. Pasteurized A. muciniphila also slightly decreased body weight by 2.27 kg, fat mass by 1.37 kg, and hip circumference by 2.63 cm compared to baseline. Additionally, A. muciniphila reduced blood markers for liver dysfunction and inflammation, while the overall gut microbiome structure remained unaffected.

This proof-of-concept study demonstrates that supplementation with A. muciniphila is safe, well-tolerated, and improves several metabolic parameters in overweight/obese insulin-resistant individuals.

The study was a single-center pilot study with a relatively small number of participants completing the trial (32 out of 40 enrolled).


Prebiotic Inulin Supplementation and Peripheral Insulin Sensitivity in adults at Elevated Risk for Type 2 Diabetes: A Pilot Randomized Controlled Trial

Inulin supplementation did not improve peripheral insulin sensitivity in adults at risk for type 2 diabetes.

unfavorable-cue: "elevated risk" | no-difference-cue: "did not improve"

Does inulin supplementation improve glucose metabolism and reduce the risk of type 2 diabetes in adults at elevated risk?

Hypothesis: The study aimed to determine the efficacy of inulin supplementation to improve glucose metabolism and reduce type 2 diabetes risk.

Adults at risk for type 2 diabetes (n=24, BMI: 31.3 ± 2.9 kg/m², age: 54.4 ± 8.3 years) were enrolled in a 6-week controlled feeding trial. Participants consumed either 10 g/day of inulin or 10 g/day of maltodextrin (placebo). Assessments included peripheral insulin sensitivity, fasting glucose, insulin, HOMA-IR, in vivo skeletal muscle substrate preference, copy number, intestinal permeability, and endotoxin concentrations.

Participant retention was 92%. Fasting insulin concentrations showed a reduction with inulin (Δ-2.9) compared to an increase with placebo (Δ2.3), but this was attenuated after adjusting for baseline differences. HOMA-IR reduction with inulin (Δ-0.40) remained significant after adjusting for baseline values, compared to an increase with placebo (Δ0.27). Gut 16s increased with inulin supplementation (Δ3.1e) and decreased with placebo (Δ-8.9e). Despite these changes, inulin supplementation did not improve peripheral insulin sensitivity.

Inulin supplementation did not improve peripheral insulin sensitivity in adults at elevated risk for type 2 diabetes, despite some observed changes in fasting insulin, HOMA-IR, and gut 16s. These findings suggest that larger investigations into inulin and insulin sensitivity in this population may not be warranted.

The study was a pilot trial with a small sample size. There was a baseline difference in fasting insulin between the groups.


Beetroot Juice and Exercise Capacity: A Systematic Review and Meta-Analysis

Beetroot juice supplementation can improve exercise capacity and lower blood pressure in individuals with COPD.

Does beetroot juice supplementation improve exercise capacity and cardiovascular parameters in patients with chronic obstructive pulmonary disease (COPD)?

Hypothesis: Beetroot juice supplementation will improve exercise capacity and cardiovascular parameters in COPD patients, with potential differences in effects based on study design (parallel vs. crossover trials).

A systematic review and meta-analysis was conducted by searching Scopus, Lilacs, PubMed, Embase, Web of Science, CENTRAL, and Science Direct databases up to December 30, 2024. Two independent reviewers extracted data on participant characteristics, supplementation protocols, exercise capacity, and cardiovascular parameters from studies on nitrate-rich beetroot juice in COPD patients. Data synthesis involved subgroup and sensitivity analyses, meta-regression, and stratified random effects meta-analyses. Risk of bias was assessed using RoB2, and evidence certainty with GRADE methodology.

Twelve studies involving 357 participants were included. Beetroot juice significantly improved exercise capacity (standardized mean difference [SMD], 0.31). Stratified analysis showed greater benefits in parallel RCTs (SMD, 0.52) compared to crossover trials (SMD, 0.06). BJ also reduced systolic blood pressure by 5.33 mmHg and diastolic blood pressure by 3.01 mmHg.

This meta-analysis provides strong evidence that beetroot juice improves exercise capacity and key cardiovascular parameters in COPD patients. Stratifying results by study design addressed previous methodological limitations, establishing a reliable foundation for clinical application.

The abstract does not explicitly state limitations of the current meta-analysis, but it does suggest the need for standardized long-term studies to confirm findings and elucidate dose-response relationships.


Therapeutic potential of beetroot juice in peripheral artery disease (review of the nitrate–nitrite–NO pathway)

Beetroot juice may improve several markers of cardiovascular health and exercise performance relevant to peripheral artery disease.

What are the potential therapeutic effects of beetroot juice (BRJ) in the management of peripheral artery disease (PAD)?

Hypothesis: Beetroot juice, rich in nitrate and betaine, may offer therapeutic benefits for PAD by increasing nitric oxide (NO) bioavailability through the nitrate-nitrite-NO pathway, thereby improving blood flow and other physiological functions.

This is a review article that explores the potential therapeutic effects of beetroot juice in PAD management by examining existing evidence related to its bioactive compounds and their mechanisms of action, particularly the nitrate-nitrite-NO pathway.

The review indicates that beetroot juice can improve exercise performance, lower blood pressure, improve endothelial function, enhance skeletal muscle microvascular function, and improve central autonomic nervous system function.

Beetroot and its rich bioactive compounds show promise as a novel supportive therapy for improving peripheral artery disease.

The abstract does not explicitly state any limitations of the review itself, but rather focuses on the potential benefits of beetroot juice.


Impact of dietary nitrate supplementation on exercise capacity and cardiovascular parameters: a systematic review and meta-analysis

Dietary nitrate supplementation may lower blood pressure and improve exercise capacity during pulmonary rehabilitation, but its short-term impact on exercise capacity is inconsistent.

Does dietary nitrate supplementation improve exercise capacity and cardiovascular parameters in individuals with respiratory disease?

Hypothesis: Dietary nitrate supplementation, often from beetroot juice, may enhance exercise performance and endothelial function in people with respiratory disease.

A systematic review and meta-analysis was conducted by searching PubMed, CINAHL, MEDLINE (Ovid), Cochrane, and Embase for clinical trials up to March 2021. Two independent authors screened and extracted data from studies evaluating dietary nitrate supplementation's efficacy on cardiovascular parameters and exercise capacity in chronic respiratory conditions. Eleven studies (two randomized controlled trials, nine crossover trials) with 282 participants were included after full-text review.

Pooled analysis showed dietary nitrate supplementation reduced systolic blood pressure by -3.39 mm Hg, diastolic blood pressure by -2.20 mm Hg, and mean arterial pressure by -4.40 mm Hg. It increased walk distance in the context of pulmonary rehabilitation (standardized mean difference 0.47), but no effect was found in short-term studies (standardized mean difference 0.08).

Dietary nitrate supplementation may beneficially affect blood pressure and enhance exercise capacity when combined with pulmonary rehabilitation. However, short-term studies do not consistently show a benefit on exercise capacity.

The review included a relatively small number of studies (11) and participants (282). Only one large study (n=122) was conducted in the context of pulmonary rehabilitation, while others were single-dose or short-term.


Effectiveness and safety of non-steroidal anti-inflammatory drugs and opioid treatment for knee and hip osteoarthritis: network meta-analysis

Topical diclofenac is a safer and effective first-line option for knee osteoarthritis, while some oral NSAIDs are effective but carry higher risks, and opioids generally offer more harm than benefit.

unfavorable-cue: "increased adverse event risk" | favorable-cue: "benefits"

What are the effectiveness and safety profiles of different NSAID, opioid, and paracetamol preparations and doses for knee and hip osteoarthritis pain and physical function?

Hypothesis: The study aimed to identify effective and safe drug options at their lowest possible doses for osteoarthritis.

This was a systematic review and network meta-analysis of 192 randomized trials, comprising 102,829 participants, published in English with at least 100 patients per group. The trials evaluated NSAIDs, opioids, or paracetamol for osteoarthritis. Data on pain, physical function, and safety outcomes were extracted and assessed for bias. Bayesian random effects models were used for network meta-analysis, comparing active treatments to oral placebo.

Five oral preparations (diclofenac 150 mg/day, etoricoxib 60 and 90 mg/day, rofecoxib 25 and 50 mg/day) had a ≥99% probability of exceeding the minimal clinically relevant pain reduction. Topical diclofenac (70-81 and 140-160 mg/day) had a ≥92.3% probability, while all opioids had a ≤53% probability of achieving this pain reduction. Increased risk of dropouts due to adverse events was observed in 18.5% of oral NSAIDs, 0% of topical NSAIDs, and 83.3% of opioids. An increased risk of any adverse event was found in 29.8% of oral NSAIDs, 0% of topical NSAIDs, and 89.5% of opioids. Oxymorphone 80 mg/day showed the highest risk for dropouts due to adverse events (51%) and any adverse event (88%).

Etoricoxib 60 mg/day and diclofenac 150 mg/day appear to be the most effective oral NSAIDs for osteoarthritis pain and function, but may not be suitable for long-term use or patients with comorbidities due to increased adverse event risk. Topical diclofenac 70-81 mg/day is effective and generally safer, making it a potential first-line treatment for knee osteoarthritis. The harms of opioid treatment for osteoarthritis likely outweigh its clinical benefits.

The abstract does not explicitly state limitations of the study beyond the inherent risks associated with certain treatments for specific patient populations.


The topical 5% lidocaine medicated plaster in localized neuropathic pain: a reappraisal of the clinical evidence

Lidocaine Pain Relief Patch;Topical Lidocaine

The 5% lidocaine medicated plaster is an effective and safe first-line treatment for localized neuropathic pain, especially beneficial for vulnerable patients.

What is the current clinical evidence regarding the efficacy and safety of the topical 5% lidocaine medicated plaster for localized neuropathic pain (LNP)?

Hypothesis: The review aims to provide an updated overview of the clinical evidence for the 5% lidocaine medicated plaster in treating LNP.

This review synthesized clinical evidence from randomized, controlled, and open-label clinical studies, real-life daily clinical practice, and case series.

The 5% lidocaine medicated plaster effectively relieves pain in postherpetic neuralgia. A large open-label controlled study indicated it is as effective as systemic pregabalin in postherpetic neuralgia and painful diabetic polyneuropathy, with better tolerability. Patients using the plaster synchronously experienced improved analgesia and fewer side effects. The plaster provides continued benefit for up to 7 years and is effective in other LNP conditions. Minor application-site reactions are common, with minimal risk of systemic adverse events or drug-drug interactions.

The 5% lidocaine medicated plaster is efficacious and safe for LNP, offering particular clinical benefit for elderly and/or medically compromised patients due to its low incidence of adverse events, although further well-controlled studies are needed.

The review acknowledges that further well-controlled studies are warranted despite the current evidence.


Topical capsaicin (high concentration) for chronic neuropathic pain in adults

Capsaicin Pain Relief Cream;Topical Capsaicin

High-concentration topical capsaicin offers some pain relief for certain neuropathic conditions, but the overall benefit is modest and the evidence quality is low.

What is the efficacy and tolerability of topically applied, high-concentration (8%) capsaicin in chronic neuropathic pain in adults?

Hypothesis: High-concentration (8%) capsaicin patches, applied as a single dose, will provide sustained pain relief for chronic neuropathic pain by rapidly desensitizing cutaneous nociceptors, with benefits lasting approximately 12 weeks.

This systematic review updated a previous review by searching CENTRAL, MEDLINE, Embase, clinical trials registries, and a pharmaceutical company's website up to June 10, 2016. It included randomized, double-blind, placebo-controlled studies of at least 6 weeks' duration using high-concentration (5% or more) topical capsaicin for neuropathic pain. Two independent reviewers extracted data on efficacy (Patient Global Impression of Change, pain intensity reduction of at least 30% or 50%) and adverse events, and assessed study quality. Pooled analysis used dichotomous data to calculate risk ratio and numbers needed to treat (NNT). The quality of evidence was assessed using GRADE.

Eight studies involving 2488 participants were included. For postherpetic neuralgia, about 10% more participants reported much or very much improvement with high-concentration capsaicin than 'active' placebo at 8 and 12 weeks (NNT 8.8 and 7.0 respectively; moderate quality evidence). Similarly, about 10% more participants achieved at least 30% or 50% pain intensity reduction (NNT 10-12; very low quality evidence). For painful HIV-neuropathy, one study showed 27% improved with capsaicin vs 10% with 'active' placebo at 12 weeks, and about 10% more participants had at least 30% pain reduction (NNT 11; very low quality evidence). One study on peripheral diabetic neuropathy also reported about 10% more participants improved at 8 and 12 weeks. Local adverse events were common, but serious adverse events were similar between active treatment (3.5%) and control (3.2%).

High-concentration topical capsaicin provided moderate or substantial pain relief for postherpetic neuralgia, HIV-neuropathy, and painful diabetic neuropathy in a greater proportion of participants compared to control. However, the quality of evidence was moderate to very low, and the additional proportion of beneficiaries was not large. For those who did benefit, improvements in sleep, fatigue, depression, and quality of life were observed.

The quality of evidence for efficacy outcomes was downgraded due to sparse data, imprecision, possible effects of imputation methods, and susceptibility to publication bias. Efficacy outcomes were inconsistently reported across studies, leading to incomplete data for most analyses. One study was judged at high risk of bias due to small size.


Efficacy of Palmitoylethanolamide for Pain: A Meta-Analysis

Palmitoylethanolamide (PEA) shows promise for pain reduction, but more rigorous research is needed to confirm its benefits and safety.

Does palmitoylethanolamide (PEA) effectively reduce pain in randomized, controlled trials?

Hypothesis: The researchers hypothesized that PEA would be an effective analgesic agent for treating pain.

This meta-analysis systematically reviewed randomized, controlled trials from PubMed and Embase investigating PEA's effect on pain scores. The primary outcome was the weighted mean difference in visual analog pain scales comparing PEA to inactive controls. Ten studies with 786 PEA patients and 512 controls were identified, with eight trials included in the meta-analysis.

PEA treatment resulted in a significantly greater pain reduction compared to inactive control conditions, with a weighted mean difference of 2.03. Factors such as placebo control, blinding, concomitant treatments, and PEA duration or dose did not influence its measured efficacy. All-cause dropout was non-significantly lower in the PEA group.

PEA may be a useful and generally well-tolerated treatment for pain in research populations. However, more well-designed, randomized, placebo-controlled trials are needed to confirm its efficacy and identify potential adverse events.

The meta-analysis was based on a relatively small number of trials with varied pain conditions and trial designs. The overall quality of the underlying studies and the assessment of side effects were often poor.


Dietary supplements for treating osteoarthritis: a systematic review and meta-analysis

High-Bioavailability Curcumin;Pycnogenol Pine Bark Extract;D-Glucosamine;Boswellia Serrata Extract;MSM (Methylsulfonylmethane);Osteo Bi-Flex (Triple Strength + Joint Shield);Glucosamine + Chondroitin (+ MSM);MSM (OptiMSM)

While some dietary supplements may offer short-term pain relief for osteoarthritis, their long-term effectiveness is not clinically important, and the quality of evidence varies.

What is the efficacy and safety of dietary supplements for patients with osteoarthritis?

Hypothesis: The study implicitly hypothesized that some dietary supplements would demonstrate efficacy and safety in treating osteoarthritis.

This was an intervention systematic review with random effects meta-analysis and meta-regression. Researchers searched MEDLINE, EMBASE, Cochrane Register of Controlled Trials, Allied and Complementary Medicine, and Cumulative Index to Nursing and Allied Health Literature from inception to April 2017. They included randomized controlled trials comparing oral supplements with placebo for hand, hip, or knee osteoarthritis.

Of 20 supplements in 69 studies, 7 (collagen hydrolysate, passion fruit peel extract, curcumin, pycnogenol, and L-carnitine) showed large (>0.80) and clinically important effects for short-term pain reduction. Six others (undenatured type II collagen, avocado soybean unsaponifiables, methylsulfonylmethane, diacerein, glucosamine, and chondroitin) showed statistically significant but unclear clinical importance for pain. Only green-lipped mussel extract and undenatured type II collagen had clinically important effects on pain at medium term, with no supplements showing long-term clinically important effects. Chondroitin showed statistically significant but not clinically important structural improvement (effect size -0.30). Safety outcomes were similar between supplements and placebo, except for diacerein. The overall analysis indicated moderate and clinically meaningful short-term effects on pain and function, though evidence quality was very low.

Some supplements showed large short-term treatment effects for osteoarthritis pain and function, while widely used supplements like glucosamine and chondroitin had small or no clinically important effects. No supplements demonstrated clinically important effects on pain and function at medium-term and long-term follow-ups. The quality of evidence varied widely.

The quality of evidence ranged from very low to high, and the overall analysis for short-term effects was based on very low quality evidence. Some supplements with large treatment effects had a limited number of studies and participants.


Efficacy of methylsulfonylmethane (MSM) in osteoarthritis pain of the knee: a pilot clinical trial

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

MSM may help reduce pain and improve physical function in people with knee osteoarthritis over a short period.

Does methylsulfonylmethane (MSM) reduce pain and improve physical function in individuals with knee osteoarthritis?

Hypothesis: The study implicitly hypothesizes that MSM will be beneficial for arthritis symptoms, specifically pain and physical function in knee osteoarthritis.

This was a randomized, double-blind, placebo-controlled pilot clinical trial. Fifty men and women aged 40-76 with knee osteoarthritis pain were randomized to receive either 3g of MSM twice daily (6g/day total) or a placebo for 12 weeks. Outcomes measured included the WOMAC visual analogue scale (pain, stiffness, physical function, total symptoms), patient and physician global assessments, and SF-36 for quality of life.

Compared to placebo, MSM significantly decreased WOMAC pain and physical function impairment. No significant changes were observed in WOMAC stiffness or aggregated total symptoms scores. MSM also improved the ability to perform activities of daily living as assessed by the SF-36.

MSM (6g/day) improved symptoms of pain and physical function during the 12-week intervention without major adverse events.

The benefits and safety of MSM in managing osteoarthritis and its long-term use cannot be confirmed from this pilot trial.


Self-Administered Acupressure for Chronic Low Back Pain: A Randomized Controlled Pilot Trial

Self-administered acupressure shows promise for reducing pain and fatigue in people with chronic low back pain.

Can self-administered acupressure reduce fatigue, pain, sleep problems, and disability in individuals with chronic low back pain (CLBP)?

Hypothesis: Self-administered acupressure, specifically relaxing and stimulating types, will improve fatigue, pain, sleep, and reported disability in individuals with CLBP.

A randomized pilot trial (N=67) assigned participants to six weeks of either relaxing acupressure, stimulating acupressure, or usual care. Outcomes measured included fatigue (Brief Fatigue Inventory), pain (Brief Pain Inventory), sleep (Pittsburgh Sleep Quality Index), and reported disability (Roland Morris Scale). An intent-to-treat analysis using general linear models was performed.

Baseline characteristics were similar across all groups. Both acupressure groups showed positive improvement in pain compared to usual care, with pain reduced by 35-36%. Stimulating acupressure also led to improved fatigue compared to usual care. Minimal adverse events were reported, primarily due to applying too much pressure.

This pilot study suggests that self-administered acupressure may be effective in reducing pain and fatigue in individuals with chronic low back pain.

This was a small pilot study, which limits the generalizability of the findings.


Low-dose lithium uptake promotes longevity in humans and metazoans

All-in-One Longevity Formulation;Lithium Orotate (low-dose)

Low levels of lithium in drinking water are associated with lower mortality in humans and extend the lifespan of roundworms.

Does low-dose lithium exposure affect mortality in metazoans and humans?

Hypothesis: Low-dose lithium exposure may affect mortality in both metazoans and mammals.

The study used weighted regression analysis on a large Japanese observational cohort to identify effects of tap water-derived lithium uptake on overall mortality. Separately, Caenorhabditis elegans (roundworms) were exposed to comparable lithium concentrations, and their mortality was quantified.

In humans, an inverse correlation was found between drinking water lithium concentrations and all-cause mortality in 18 Japanese municipalities, involving 1,206,174 individuals. Exposure to a comparably low concentration of lithium chloride extended the lifespan of C. elegans.

Long-term low-dose exposure to lithium may have anti-aging capabilities and decreases mortality in evolutionarily distinct species.

The abstract does not explicitly state limitations of the study.


Hyperbaric oxygen therapy increases telomere length and decreases immunosenescence in isolated blood cells: a prospective trial

Hyperbaric oxygen therapy significantly increased telomere length and reduced senescent cell percentages in various immune cells in healthy older adults.

favorable-cue: "significantly increased telomere"

Does hyperbaric oxygen therapy (HBOT) affect telomere length and senescent cell concentrations in healthy aging adults?

Hypothesis: Repeated intermittent hyperoxic exposures, such as certain HBOT protocols, may induce regenerative effects that could impact telomere length and cellular senescence.

Thirty-five healthy adults, aged 64 and older, received 60 daily HBOT exposures. Whole blood samples were collected at baseline, after 30 and 60 sessions, and 1-2 weeks post-HBOT. Peripheral blood mononuclear cells (PBMCs) were analyzed for telomere length and senescence.

Telomere length in T helper, T cytotoxic, natural killer, and B cells increased significantly by over 20% after HBOT. B cell telomere length showed the most significant increase, rising by 25.68% at session 30, 29.39% at session 60, and 37.63% post-HBOT. There was a significant decrease in senescent T helper cells by -37.30% post-HBOT and senescent T-cytotoxic cells by -10.96% post-HBOT.

Hyperbaric oxygen therapy (HBOT) may induce significant senolytic effects in aging populations, including increasing telomere length and clearing senescent cells.

The study involved a specific HBOT protocol and a relatively small sample size of healthy, independently living adults, which may limit generalizability.


Topical NSAIDs for chronic musculoskeletal pain in adults

In studies lasting 6 to 12 weeks, topical diclofenac and topical ketoprofen were significantly more effective than carrier for reducing pain; about 60% of participants had much reduced pain.


Efficacy and safety of different topical diclofenac formulations for knee osteoarthritis: a meta-analysis

Topical diclofenac formulations (gel, solution, patch) significantly improve pain and function in knee osteoarthritis compared to placebo. All formulations were well-tolerated.


High-concentration topical capsaicin used to treat postherpetic neuralgia, HIV-neuropathy, and painful diabetic neuropathy generated more participants with moderate or substantial levels of pain relief than control.


Individual responses to topical ibuprofen gel or capsaicin cream for painful knee osteoarthritis: a series of n-of-1 trials

Mean pain reduction was 1.2 on ibuprofen and 1.6 on capsaicin... 59% of people displayed a greater response to one treatment over the other.


Review of lidocaine patch 5% studies in the treatment of postherpetic neuralgia

In patients with PHN, the lidocaine patch 5% has demonstrated relief of pain and tactile allodynia with a minimal risk of systemic adverse effects... recommended as a first-line therapy.


Topical lidocaine for neuropathic pain in adults

In all but one study, evidence indicated that lidocaine was better than placebo for some measure of pain relief. Clinical experience also supports efficacy in some patients.


Comparison of diclofenac gel, ibuprofen gel, and ibuprofen gel with levomenthol for topical treatment of musculoskeletal pain

Topical Menthol (Cooling Counterirritant);Topical Methyl Salicylate + Menthol (Medicated Patch)

Both ibuprofen/levomenthol and diclofenac gels provided superior global pain relief compared with ibuprofen gel, with a shorter median time to significant pain relief. Only ibuprofen/levomenthol gel provided cooling for up to 2 hours.


Efficacy and safety of topical diclofenac/menthol gel for ankle sprain: a randomized, double-blind, placebo- and active-controlled trial

No significant improvement was observed with topical 1% diclofenac/3% menthol gel compared with placebo, 1% diclofenac, or 3% menthol gel in treating pain from ankle sprain.

no-difference-cue: "no significant improvement"


Topical non-steroidal anti-inflammatory drug use for acute musculoskeletal pain: a scoping review

Topical Methyl Salicylate + Menthol (Medicated Patch)

Findings suggest topical NSAIDs may be effective and well tolerated for managing acute musculoskeletal pain; interventions included ketoprofen gel, methyl salicylate/1-menthol patch, and diclofenac epolamine patch.


Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis (GAIT)

For patients with moderate-to-severe knee pain, the glucosamine–chondroitin combination produced a significantly higher response than placebo (79.2% vs 54.3%, P=0.002).


Combined chondroitin sulfate and glucosamine for painful knee osteoarthritis: a non-inferiority trial versus celecoxib (MOVES)

Chondroitin sulfate plus glucosamine matched celecoxib, cutting WOMAC pain ~50% at 6 months with a good safety profile.


Chondroitin for osteoarthritis (Cochrane systematic review of 43 trials)

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

Chondroitin (alone or with glucosamine) was better than placebo for osteoarthritis pain in short-term trials, with a lower risk of serious adverse events.


Efficacy and safety of 5-Loxin (AKBA-enriched Boswellia serrata) for osteoarthritis of the knee

Osteo Bi-Flex (Triple Strength + Joint Shield)

Both doses of 5-Loxin produced clinically and statistically significant improvements in osteoarthritis pain and function, with reduced cartilage-degrading MMP-3.


Aging-associated decline of phosphatidylcholine synthesis is a malleable trigger of natural mitochondrial aging

Ectopic boosting of phosphatidylcholine via diet restored late-life mitochondrial integrity in nematodes and reinstated metabolic resilience in human cell cultures — identifying PC decline as a malleable driver of mitochondrial aging.


Ageing-induced alterations in lipid/phospholipid profiles of brain and liver mitochondria

In aged rat brain mitochondria the phosphatidylcholine content decreased and respiration was significantly impaired in old animals.


Assessment of Total Choline Intakes in the United States (NHANES)

Suboptimal intakes of choline are prevalent: only about 11% of Americans aged 2+ achieved the adequate intake for choline.


Combined chondroitin sulfate and glucosamine for painful knee osteoarthritis: a multicentre, randomised, double-blind, non-inferiority trial versus celecoxib

In the MOVES trial, glucosamine plus chondroitin had efficacy comparable to celecoxib in reducing pain, stiffness and functional limitation after 6 months in painful knee osteoarthritis, with a good safety profile.


Effectiveness and safety of glucosamine and chondroitin for the treatment of osteoarthritis: a meta-analysis of randomized controlled trials

Journal of Orthopaedic Surgery and Research

A meta-analysis of randomized controlled trials found glucosamine improved stiffness outcomes and chondroitin relieved pain and physical function versus placebo in osteoarthritis.


The efficacy of curcumin in relieving osteoarthritis: A meta-analysis of meta-analyses

Pooling 11 meta-analyses, curcuminoid supplementation significantly reduced VAS and WOMAC pain scores and improved joint mobility and stiffness in osteoarthritis patients.


Efficacy and safety of curcumin therapy for knee osteoarthritis: A Bayesian network meta-analysis

A Bayesian network meta-analysis concluded curcumin, alone or combined, has good clinical efficacy and safety for knee osteoarthritis.


Evaluation of the analgesic effect of α-lipoic acid in treating pain disorders: A systematic review and meta-analysis of randomized controlled trials

A systematic review and meta-analysis of RCTs found alpha-lipoic acid reduced stabbing pain, burning, paraesthesia and numbness versus placebo in diabetic polyneuropathy by both oral and intravenous routes.


Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a meta-analysis

This meta-analysis found alpha-lipoic acid (600 mg/day) over 3 weeks safely and significantly improved neuropathic symptoms and deficits to a clinically meaningful degree in symptomatic diabetic polyneuropathy.


Acetyl-L-carnitine improves pain, nerve regeneration, and vibratory perception in patients with chronic diabetic neuropathy: an analysis of two randomized placebo-controlled trials

A pooled analysis of two randomized placebo-controlled trials showed acetyl-L-carnitine alleviated symptoms, particularly pain, and improved nerve fiber regeneration in established diabetic neuropathy.


Effects of omega-3 fatty acids on chronic pain: a systematic review and meta-analysis

This systematic review and meta-analysis found omega-3 supplementation produced a clinically meaningful, time-dependent reduction in chronic pain, particularly at moderate doses.

favorable-cue: "reduction in chronic pain"


Omega-3 polyunsaturated fatty acids and the treatment of rheumatoid arthritis: a meta-analysis

This meta-analysis found omega-3 PUFAs above 2.7 g/day for over 3 months significantly reduced NSAID consumption in rheumatoid arthritis patients.


Treatment of osteoarthritis with Pycnogenol. The SVOS (San Valentino Osteo-arthrosis Study)

In the randomized SVOS study, Pycnogenol reduced osteoarthritis symptoms and cut anti-inflammatory drug use by 58% versus 1% with placebo.

favorable-cue: "reduced osteoarthritis symptoms"


Review on Sustained Relief of Osteoarthritis Symptoms with a Proprietary Extract from Pine Bark, Pycnogenol

Across three clinical studies, pine bark extract (Pycnogenol) relieved pain, improved stiffness and mobility, and spared NSAID use in osteoarthritis patients.


Quercetin in men with category III chronic prostatitis: a preliminary prospective, double-blind, placebo-controlled trial

In a double-blind placebo-controlled trial, the bioflavonoid quercetin was well tolerated and provided significant symptomatic improvement in most men with chronic pelvic pain syndrome.


A meta-analysis of the analgesic effects of omega-3 polyunsaturated fatty acid supplementation for inflammatory joint pain

Supplementation with omega-3 PUFAs for 3–4 months reduces patient reported joint pain intensity, minutes of morning stiffness, number of painful and/or tender joints, and NSAID consumption. The results suggest that omega-3 PUFAs are an attractive adjunctive treatment for joint pain associated with rheumatoid arthritis, inflammatory bowel disease, and dysmenorrhea.

favorable-cue: "reduces patient reported joint pain"


Marine Oil Supplements for Arthritis Pain: A Systematic Review and Meta-Analysis of Randomized Trials

The standardized mean difference suggested a favorable effect on pain (−0.24; 95% CI −0.42 to −0.07). A significant effect was found in patients with rheumatoid arthritis; the evidence was of moderate quality in rheumatoid arthritis patients.


Effects of Oral Alpha-Lipoic Acid Treatment on Diabetic Polyneuropathy: A Meta-Analysis and Systematic Review

ALA treatment had favorable effects on diabetic sensorimotor peripheral neuropathy by reducing sensory symptoms, and it resulted in a dose-dependent response relative to the placebo for the total symptom score and the global satisfaction score.


Acetyl-L-carnitine in the treatment of peripheral neuropathic pain: a systematic review and meta-analysis of randomized controlled trials

Compared with placebo, ALC significantly reduced VAS scores of peripheral neuropathic pain patients (MD 1.20; 95% CI 0.68–1.72). The current evidence suggests that ALC has a moderate effect in reducing pain measured on VAS in PNP patients with acceptable safety.


Acetyl-L-carnitine for the treatment of diabetic peripheral neuropathy

ALC reduced pain more than placebo, measured on a 0- to 100-mm VAS (MD −9.16, 95% CI −16.76 to −1.57); at doses greater than 1500 mg/day, ALC reduced pain more than placebo (MD −14.93, 95% CI −19.16 to −10.70).


The role of diet and non-pharmacologic supplements in the treatment of chronic neuropathic pain: A systematic review

Regarding diabetic peripheral neuropathy, our review supports the use of alpha-lipoic acid, acetyl-l-carnitine, and vitamin D. Dietary interventions, vitamins, and nutritional supplementation are playing an increasingly important role in the management of neuropathic pain.


Magnesium in Migraine Prophylaxis—Is There an Evidence-Based Rationale? A Systematic Review

This systematic review provides Grade C (possibly effective) evidence for prevention of migraine with magnesium. Prophylactic treatment of migraine by means of high levels of magnesium dicitrate (600 mg) seems to be a safe and cost efficient strategy in clinical use.


Effects of Intravenous and Oral Magnesium on Reducing Migraine: A Meta-analysis of Randomized Controlled Trials

Oral magnesium significantly alleviated the frequency and intensity of migraine (ORs = 0.20 and 0.27). Intravenous and oral magnesium should be adapted as parts of a multimodal approach to reduce migraine.


Coenzyme Q10 supplementation for prophylaxis in adult patients with migraine—a meta-analysis

CoQ10 supplementation reduced the duration of headache attacks compared with the control group, and reduced the frequency of migraine headache (MD −1.52; 95% CI −2.40 to −0.65). CoQ10 appears to have beneficial effects in reducing duration and frequency of migraine attack.


Nutritional Interventions in the Management of Fibromyalgia Syndrome

Among nonpharmacological strategies for fibromyalgia (characterized by widespread chronic pain), clinical trials with vitamin D, magnesium, iron and coenzyme Q10 supplementation show promising results.


Creatine supplementation in fibromyalgia: a randomized, double-blind, placebo-controlled trial

Creatine supplementation increased intramuscular phosphorylcreatine content and improved lower- and upper-body muscle function in fibromyalgia patients. These findings introduce creatine supplementation as a useful dietary intervention to improve muscle function in fibromyalgia patients.


Effect of vitamin D supplementation in chronic widespread pain: a systematic review and meta-analysis

Pooled results demonstrated a significantly lower VAS in chronic widespread pain patients who received vitamin D treatment compared with those who received placebo (MD 0.46; 95% CI 0.09–0.89). We conclude that vitamin D supplementation is able to decrease pain scores and improve pain.


Does vitamin D supplementation alleviate chronic nonspecific musculoskeletal pain? A systematic review and meta-analysis

We found no effect of vitamin D supplementation (SMD 0.004; 95% CI −0.248 to 0.256) on pain in chronic nonspecific musculoskeletal pain patients—a balancing finding indicating benefit is most likely where baseline vitamin D status is low.

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


Palmitoylethanolamide in the Treatment of Chronic Pain: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials

PEA was found to reduce pain scores relative to comparators in a pooled estimate, with a standardized mean difference of 1.68 (95% CI 1.05 to 2.31). The results suggest that PEA is an effective and well-tolerated treatment for chronic pain.


Efficacy of Palmitoylethanolamide for Pain: A Meta-Analysis

PEA was associated with significantly greater pain reduction compared to inactive control conditions (WMD 2.03, 95% CI 1.19–2.87, P < 0.001). PEA may be a useful treatment for pain and is generally well tolerated.


Effectiveness of Boswellia and Boswellia extract for osteoarthritis patients: a systematic review and meta-analysis

BMC Complementary Medicine and Therapies

Boswellia and its extract may relieve the pain (VAS WMD −8.33; 95% CI −11.19 to −5.46) and stiffness and improve joint function. Boswellia and its extract may be an effective and safe treatment option for patients with osteoarthritis.


Dietary supplements for treating osteoarthritis: a systematic review and meta-analysis

Boswellia serrata extract, curcumin, pycnogenol and L-carnitine demonstrated large and clinically important effects for pain reduction at short term; supplements provided moderate and clinically meaningful treatment effects on pain and function in osteoarthritis at short term.


Methylsulfonylmethane Improves Knee Quality of Life in Participants with Mild Knee Pain: A Randomized, Double-Blind, Placebo-Controlled Trial

The total Japanese Knee Osteoarthritis Measure scores at 12 weeks differed significantly between the MSM and placebo groups (p = 0.046). MSM oral consumption improved both knee and systemic health conditions in participants who experienced mild knee pain.


Efficacy of methylsulfonylmethane supplementation on osteoarthritis of the knee: a randomized controlled study

BMC Complementary and Alternative Medicine

Patients with osteoarthritis of the knee taking MSM for 12 weeks showed an improvement in pain and physical function (WOMAC total score difference 15.0 mm; p = 0.03).


Effectiveness and safety of glucosamine and chondroitin for the treatment of osteoarthritis: a meta-analysis of randomized controlled trials

Oral chondroitin is more effective than placebo on relieving pain and improving physical function; glucosamine showed an effect on the stiffness outcome in patients with knee and/or hip osteoarthritis.


Association of Pharmacological Treatments With Long-term Pain Control in Patients With Knee Osteoarthritis: A Systematic Review and Meta-analysis

Associations with decreases in pain were found for glucosamine sulfate (SMD −0.29; 95% CrI −0.49 to −0.09); the association with pain improvement remained significant for glucosamine sulfate when trials at high risk of bias were excluded.


Efficacy and safety of the combination of glucosamine and chondroitin for knee osteoarthritis: a systematic review and meta-analysis

Archives of Orthopaedic and Trauma Surgery

The combination of glucosamine and chondroitin showed a statistically significant advantage in total WOMAC score versus placebo (MD −12.04). The combination is effective and superior to other treatments in knee osteoarthritis to a certain extent.


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

Following treatment with Pycnogenol patients reported an improvement of WOMAC index (p < 0.05) and a significant alleviation of pain by visual analogue scale (p < 0.04); the placebo had no effect. Pycnogenol improves symptoms and is able to spare NSAIDs.

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


Treatment of osteoarthritis with Pycnogenol. The SVOS (San Valentino Osteo-arthrosis Study)

The global WOMAC score decreased by 56% (p < 0.05) in the Pycnogenol group versus 9.6% in placebo, and use of analgesic drugs decreased by 58% in the treatment group versus 1% under placebo.


Therapeutic effects of saffron (Crocus sativus L) on female reproductive system disorders: A systematic review

Retrieved studies indicated that saffron can alleviate the symptoms of patients suffering from dysmenorrhea and premenstrual syndrome, particularly due to phytochemical ingredients such as crocin, crocetin, and safranal.


Tart Cherry Supplementation and Recovery From Strenuous Exercise: A Systematic Review and Meta-Analysis

International Journal of Sport Nutrition and Exercise Metabolism

Tart cherry supplementation had a small beneficial effect in reducing muscle soreness (ES −0.44) and a moderate beneficial effect on recovery of muscular strength (ES −0.78). Consumption of a tart cherry supplement can aid aspects of recovery from strenuous exercise.


Efficacy and safety of tart cherry supplementary citrate mixture on gout patients: a prospective, randomized, controlled study

Participants taking the tart cherry citrate mixture experienced fewer gout flares than those in the sodium bicarbonate group (p < 0.05) and had lower C-reactive protein at week 12, suggesting tart cherry may reduce inflammation in gout.


Oral resveratrol in adults with knee osteoarthritis: A randomized placebo-controlled trial (ARTHROL).

At 3 months, the mean reduction in knee pain was -15.7 (95% confidence interval (CI), -21.1 to -10.3) in the resveratrol group and -15.2 (95% CI, -20.5 to -9.8) in the placebo group (absolute difference -0.6 [95% CI, -8.0 to 6.9]; p = 0.88).


Resveratrol supplementation improves functional performance in knee osteoarthritis by upregulating sirtuin 1: a randomized study.

Resveratrol treatment significantly reduced pain intensity and WOMAC scores, while increasing OKS scores, ROM, gait velocity, HGS, and overall SPPB performance (p < 0.05).

favorable-cue: "significantly reduced pain"


A comprehensive insight into effects of resveratrol on molecular mechanism in rheumatoid arthritis: A literature systematic review.

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease, which is characterized by massive pain and destruction of synovial joints, leads to bone erosion, damage to cartilage, and disability.


Effects of vitamin D supplementation in endometriosis: a systematic review.

Quantitative synthesis of human studies showed no significant effect of vit D intake for dysmenorrhea (2 studies, 44 vit D vs 44 placebo, mean -0.71, 95% CI -1.94, 0.51) and non-cyclic pelvic pain (2 studies, 42 vit D vs 38 placebo, mean 0.34, 95% CI -0.02, 0.71).

no-difference-cue: "no significant effect"


Antioxidant vitamins supplementation reduce endometriosis related pelvic pain in humans: a systematic review and meta-analysis.

These findings suggest that antioxidant vitamins may alleviate pain in endometriosis patients by reducing inflammation.


Astrocytic spermidine insufficiency contributes to enhanced pain sensitivity associated with ApoE4.

Mechanistically, spermidine suppressed Nos2 expression by inhibiting the NF-κB pathway in astrocytes, thereby alleviating neuropathic pain.


Spermidine ameliorates osteoarthritis via altering macrophage polarization.

However, the specific protective mechanism of SPD in osteoarthritis (OA) remains unclear.


Effectiveness and safety of glucosamine and chondroitin for the treatment of osteoarthritis: a meta-analysis of randomized controlled trials.

Given the effectiveness of these symptomatic slow-acting drugs, oral chondroitin is more effective than placebo on relieving pain and improving physical function.


Efficacy and safety of the combination of glucosamine and chondroitin for knee osteoarthritis: a systematic review and meta-analysis.

Our study confirmed that the combination of glucosamine and chondroitin is effective and superior to other treatments in knee osteoarthritis to a certain extent.


Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis.

Exploratory analyses suggest that the combination of glucosamine and chondroitin sulfate may be effective in the subgroup of patients with moderate-to-severe knee pain.


Chondroitin for osteoarthritis.

The benefit was small to moderate with an 8 point greater improvement in pain (range 0 to 100) and a 2 point greater improvement in Lequesne's index (range 0 to 24), both seeming clinically meaningful.


Efficacy of Probiotics in Irritable Bowel Syndrome: Systematic Review and Meta-analysis.

For abdominal pain, there was low certainty in the evidence for a benefit of Saccharomyces cerevisae I-3856 and Bifidobacterium strains, and very low certainty for combination probiotics, Lactobacillus, Saccharomyces, and Bacillus strains.


Efficacy of Probiotics for Irritable Bowel Syndrome: A Systematic Review and Network Meta-Analysis.

B.coagulans exhibited the highest probability to be the optimal probiotic specie in improving IBS symptom relief rate, as well as global symptom, abdominal pain, bloating, and straining scores.


Systematic review with meta-analysis: the efficacy of prebiotics, probiotics, synbiotics and antibiotics in irritable bowel syndrome.

Particular combinations of probiotics, or specific species and strains, appeared to have beneficial effects on global IBS symptoms and abdominal pain, but it was not possible to draw definitive conclusions about their efficacy.


Beetroot juice is more beneficial than sodium nitrate for attenuating muscle pain after strenuous eccentric-bias exercise.

These data suggest that BTJ supplementation is more effective than SN for attenuating muscle pain associated with EIMD, and that any analgesic effects are likely due to phytonutrients in BTJ other than nitrate, or interactions between them.


The effect of acute beetroot juice consumption prior to climbing on lower-body isokinetic and isometric strength, aerobic power, and muscle soreness among mountain climbers.

The results revealed a statistically significant decrease in DOMS in the gastrocnemius muscles 24 hours post-descending in the BRJ group compared to the control group (p = 0.003, pEta2 = 0.204).


The Effect of Nitrate-Rich Beetroot Juice on Markers of Exercise-Induced Muscle Damage: A Systematic Review and Meta-Analysis of Human Intervention Trials.

Pressure pain threshold was greater with beetroot juice 48 (SMD: 0.58, p = 0.03) and 72 h post-exercise (SMD: 0.61, p = 0.02).


Use of kersetin and fisetin flavonoids in combination with pregabalin and gabapentin in the treatment of neuropathic pain.

Fisetin Senolytic Capsules;Quercetin Capsules

Based on these findings; it is possible to say that quercetin and fisetin are potential agents that can be used alone or in combination with other effective treatments to alleviate neuropathic pain.


Analgesic Effects of Fisetin, Peimine, Astaxanthin, Artemisinin, Bardoxolone Methyl and 740 Y-P and Their Influence on Opioid Analgesia in a Mouse Model of Neuropathic Pain.

The results of our research clearly indicate that substances that inhibit all three MAPKs provide pain relief and improve opioid effectiveness, especially if they additionally block NF-κB, such as peimine, inhibit NF-κB and activate PI3K, such as fisetin, or activate Nrf2, such as astaxanthin.


Urolithin A improves mitochondrial health, reduces cartilage degeneration, and alleviates pain in osteoarthritis.

Furthermore, Urolithin A reduced disease progression in a mouse model of OA, decreasing cartilage degeneration, synovial inflammation, and pain.


Urolithin A alleviates neuropathic pain and activates mitophagy.

We showed that the autophagy flow was blocked in the spinal dorsal horn of the chronic constriction injury (CCI) mice when the most obvious pain behavior occurs.


Efficacy and Safety of Curcumin and Curcuma longa Extract in the Treatment of Arthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trial.

Curcumin and Curcuma longa Extract may improve symptoms and inflammation levels in people with arthritis.


Effect of curcumin on rheumatoid arthritis: a systematic review and meta-analysis.

Inflammation levels and clinical symptoms in patients with rheumatoid arthritis can be improved by curcumin supplementation.


The efficacy of curcumin in relieving osteoarthritis: A meta-analysis of meta-analyses.

The results strongly support curcuminoid supplementation in relieving pain, improving joint mobility and stiffness, and shortening medication usage of OA patients.


The Adjunctive Effect of Quercetin on Postoperative Pain Management Following Cesarean Section: A Randomized Controlled Study.

These findings suggest Quercetin may serve as a safe, effective adjunct in multimodal pain management protocols for cesarean delivery.


Therapeutic potential of senolytic agent quercetin in osteoarthritis: A systematic review and meta-analysis of preclinical studies.

A random-effects meta-analysis was performed on six studies using the Osteoarthritis Research Society International (OARSI) scoring system, revealing that quercetin significantly improved OA cartilage OARSI scores (SMD, -6.30 [95% CI, -9.59 to -3.01]; P = 0.0002; heterogeneity: I2 = 86%).


A Multicenter, Randomized, Double-Blinded, Placebo-Controlled Clinical Trial to Evaluate the Efficacy and Safety of a Krill Oil, Astaxanthin, and Oral Hyaluronic Acid Complex on Joint Health in People with Mild Osteoarthritis.

These findings suggest that FP-MD is well tolerated and can be effectively used to address joint pain in patients diagnosed with mild osteoarthritis, the main symptom of this condition.


Astaxanthin supplement improves clinical outcomes, quality of life, and inflammatory factors in patients with rheumatoid arthritis: a randomized clinical trial.

However, no significant differences in the pain intensity and CRP levels were found after controlling for confounding factors (P > 0.05).

no-difference-cue: "no significant differences"


Impact of olive leaf extract on pain management and functional improvement in elderly patients with knee osteoarthritis: A randomized controlled trial.

The intervention groups showed significantly more significant reductions in mean pain scores than the control group (p < 0.05).


Double-blind placebo-controlled trial of hydroxytyrosol of Olea europaea on pain in gonarthrosis.

The group administered hydroxytyrosol showed significant improvement in the Japanese Orthopedic Association score (pain measurement index) and the visual analog scale score compared to the placebo group.


Pomegranate extract alleviates disease activity and some blood biomarkers of inflammation and oxidative stress in Rheumatoid Arthritis patients.

Compared with the placebo group, POMx supplement significantly reduced the score of DAS28 (P<0.001) which could be related to the decrease in swollen (P<0.001) and tender joints (P=0.001) count, pain intensity (P=0.003) and ESR levels (P= 0.03).


The effect of pomegranate juice on clinical signs, matrix metalloproteinases and antioxidant status in patients with knee osteoarthritis.

Significant decreases in Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) total score (P = 0.01), stiffness score (P = 0.00) and physical function score (P = 0.01) were observed in PJ group after the intervention.


Pomegranate use to attenuate bone loss in major musculoskeletal diseases: an evidence-based review.

This evidence-based review highlighted the potential of pomegranate extract being used for treating bone loss in osteoporosis, osteoarthritis and rheumatoid arthritis.


The Effect of Hesperidin and Diosmin Individually or in Combination on Metabolic Profile and Neuropathy among Diabetic Patients with Metabolic Syndrome: A Randomized Controlled Trial.

Oral supplementation of hesperidin and diosmin was associated with improvement in metabolic syndrome and diabetic neuropathy and the combination of both was superior in efficacy.


Evaluation of a preemptive intervention regimen with hesperidin methyl chalcone in delayed-onset muscle soreness in young adults: a randomized, double-blinded, and placebo-controlled trial study.

Preemptive HMC supplementation may be beneficial for boosting physical performance and for the amelioration of clinical parameters related to DOMS, including pain on muscle palpation, increased blood CPK levels, and muscle strength and proprioceptive deficits, without causing adverse effects.


Is a Combination of Diosmin and Hesperidin Effective on Swelling, Pain, and Range of Motion After Total Knee Arthroplasty?

Using a diosmin and hesperidin combination in the postoperative period after TKA surgery reduces extremity swelling and pain during rest and movement, increases the degree of knee flexion, and does not cause an increase in complications.

favorable-cue: "reduces extremity swelling and pain"


Luteolin: A promising natural agent in management of pain in chronic conditions.

The data reviewed strongly support luteolin's promising benefits in pain management and raise the need for further clinical trials that can establish its role in clinical practice.


Dietary supplements for treating osteoarthritis: a systematic review and meta-analysis.

Pycnogenol Pine Bark Extract;MSM (Methylsulfonylmethane);MSM (OptiMSM)

No supplements were identified with clinically important effects on pain reduction at long term.


Randomized double-blind crossover study of the efficacy of a tart cherry juice blend in treatment of osteoarthritis (OA) of the knee.

To assess the efficacy of tart cherry juice in treating pain and other features of knee osteoarthritis (OA).


Montmorency tart cherry (Prunus cerasus L.) supplementation accelerates recovery from exercise-induced muscle damage in females.

There was also a trend for lower DOMS (p = 0.070) and for higher PPT at the rectus femoris (p = 0.071) in the MC group.


Significant Effect of Crocin on the Gene Expression of MicroRNA-21 and MicroRNA-155 in Patients with Osteoarthritis.

The current treatment aims to alleviate pain and inflammation and improve the quality of life.


Immunoregulatory Effects of Krocina™, a Herbal Medicine Made of Crocin, on Osteoarthritis Patients: A Successful Clinical Trial in Iran.

Osteoarthritis (OA) is the major cause of joint pain and disability.


Coenzyme Q10 supplementation for prophylaxis in adult patients with migraine-a meta-analysis.

CoQ10 appears to have beneficial effects in reducing duration and frequency of migraine attack.


Efficacy of CoQ10 as supplementation for migraine: A meta-analysis.

However, CoQ10 was more effective than placebo in reducing migraine days/month (P < 0.00001) and migraine duration (P = 0.009).


Efficacy of coenzyme Q10 in migraine prophylaxis: a randomized controlled trial.

CoQ10 was superior to placebo for attack-frequency, headache-days and days-with-nausea in the third treatment month and well tolerated; 50%-responder-rate for attack frequency was 14.4% for placebo and 47.6% for CoQ10 (number-needed-to-treat: 3).


Acetyl-L-carnitine for the treatment of diabetic peripheral neuropathy.

ALC reduced pain more than placebo, measured on a 0- to 100-mm VAS (MD -9.16, 95% CI -16.76 to -1.57; three studies; 540 participants; P = 0.02; I² = 56%; random-effects; very low-certainty evidence; a higher score indicating more pain).


Acetyl-L-carnitine in the treatment of peripheral neuropathic pain: a systematic review and meta-analysis of randomized controlled trials.

The current evidence suggests that ALC has a moderate effect in reducing pain measured on VAS in PNP patients with acceptable safety.


Palmitoylethanolamide and acetyl-L-carnitine act synergistically with duloxetine and pregabalin in fibromyalgia: results of a randomised controlled study.

Fibromyalgia (FM) is characterised by a form of debilitating pain that is unresponsive to standard analgesics.


Magnesium in Migraine Prophylaxis-Is There an Evidence-Based Rationale? A Systematic Review.

This systematic review provides Grade C (possibly effective) evidence for prevention of migraine with magnesium.


Effects of Intravenous and Oral Magnesium on Reducing Migraine: A Meta-analysis of Randomized Controlled Trials.

Intravenous magnesium reduces acute migraine attacks within 15 - 45 minutes, 120 minutes, and 24 hours after the initial infusion and oral magnesium alleviates the frequency and intensity of migraine.


High Dosage Omega-3 Fatty Acids Outperform Existing Pharmacological Options for Migraine Prophylaxis: A Network Meta-Analysis.

Current pharmacologic prophylactic strategies for migraine have limited efficacy and acceptability, with relatively low response rates of 40% to 50% and limited safety profiles.


Effect of omega-3 polyunsaturated fatty acids supplementation for patients with osteoarthritis: a meta-analysis.

Supplementation of n-3 PUFAs is effective to relieve pain and improve joint function in patients with OA.


Effect of Anti-Inflammatory Diets on Pain in Rheumatoid Arthritis: A Systematic Review and Meta-Analysis.

The main conclusion is that anti-inflammatory diets resulted in significantly lower pain than ordinary diets (-9.22 mm; 95% CI -14.15 to -4.29; p = 0.0002; 7 RCTs, 326 participants).

favorable-cue: "significantly lower pain"