The Effect of Probiotics on Health Outcomes in the Elderly: A Systematic Review of Randomized, Placebo-Controlled Studies.

Probiotics appear to be efficacious in modifying gut microbiota composition in healthy older adults and have moderate effects on immune function.


Impact of probiotics and prebiotics in the modulation of the major events of the aging process: A systematic review of randomized controlled trials.

Overall, most interventions resulted in improvements in certain parameters when compared to control (glucose homeostasis, cognitive function, frailty phenotype, gut microbiota profile, immune parameters), while others remained unvariable.


Lactobacillus gasseri KS-13, Bifidobacterium bifidum G9-1, and Bifidobacterium longum MM-2 Ingestion Induces a Less Inflammatory Cytokine Profile and a Potentially Beneficial Shift in Gut Microbiota in Older Adults: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study.

The probiotic maintained CD4+ lymphocytes and produced a less inflammatory cytokine profile possibly due to the changes in the microbial communities, which more closely resembled those reported in healthy younger populations.


Effects of Soluble Corn Fiber Alone or in Synbiotic Combination with LGG and the Pilus-Deficient Derivative GG-PB12 on Fecal Microbiota, Metabolism, and Markers of Immune Function: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study in Healthy Elderly (Saimes Study).

We also found significant positive effects on the immune response, evidenced by a decrease of the pro-inflammatory cytokine IL-6.


Effects of OLL2712 on Memory Function in Older Adults with Declining Memory: A Randomized Placebo-Controlled Trial.

The present study suggests that OLL2712 ingestion has protective effects against memory function decline in older adults.


Probiotics, Prebiotics, Lactoferrin, and Combination Products for Prevention of Mortality and Morbidity in Preterm Infants: A Systematic Review and Network Meta-Analysis.

Only multiple-strain probiotics were associated with reduced all-cause mortality compared with placebo (risk ratio [RR], 0.69; 95% CI, 0.56 to 0.86; risk difference [RD], -1.7%; 95% CI, -2.4% to -0.8%).

favorable-cue: "associated with reduced"


Do probiotics mitigate GI-induced inflammation and perceived fatigue in athletes? A systematic review.

Probiotic supplementation, specifically at a minimum dosage of 15 billion CFUs daily for a duration of at least 28 days, may contribute to the reduction of perceived or actual fatigue.


Thirty Years of Lactobacillus rhamnosus GG: A Review.

Furthermore LGG is able to produces both a biofilm that can mechanically protect the mucosa, and different soluble factors beneficial to the gut by enhancing intestinal crypt survival, diminishing apoptosis of the intestinal epithelium, and preserving cytoskeletal integrity.


Effect of pasteurized Akkermansia muciniphila MucT on insulin sensitivity, body composition, and GLP-1 production in subjects with metabolic syndrome: impact of low baseline gut Akkermansia levels.

The primary endpoint of whole-body insulin sensitivity (Matsuda index) did not differ after 4-months of daily administration of capsules containing 30 billion cells of pasteurizedMucT compared to placebo in the intention-to-treat subjects.


A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice.

We demonstrated that Amuc_1100, a specific protein isolated from the outer membrane of A. muciniphila, interacts with Toll-like receptor 2, is stable at temperatures used for pasteurization, improves the gut barrier and partly recapitulates the beneficial effects of the bacterium.


Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology.

A. muciniphila is associated with a healthier metabolic status and better clinical outcomes after CR in overweight/obese adults.


Akkermansia muciniphila, a New Generation of Beneficial Microbiota in Modulating Obesity: A Systematic Review.

Although there are studies that support the protective effect of this strategy, the effects on the prevention of obesity on humans are not clear yet and need more investigation.


Probiotics, Prebiotics, Synbiotics, Postbiotics, and Obesity: Current Evidence, Controversies, and Perspectives.

Bifidobacterium and Lactobacillus strains are still the most widely used probiotics in functional foods and dietary supplements, but next generation probiotics, such as Faecalibacterium prausnitzii, Akkermansia muciniphila, or Clostridia strains, have demonstrated promising results.


Action and function of Akkermansia muciniphila in microbiome ecology, health and disease.

A. muciniphila is particularly effective in increasing mucus thickness and increasing gut barrier function.


Akkermansia muciniphila: paradigm for next-generation beneficial microorganisms.

The causal evidence derived from a variety of animal models performed in different laboratories and recently was also recapitulated in a human proof-of-concept trial.


Akkermansia muciniphila: a promising target for the therapy of metabolic syndrome and related diseases.

Its specialization in mucin degradation makes it a key microorganism that maintains intestinal mucosal barrier function.


Extracellular Vesicles from Child Gut Microbiota Enter into Bone to Preserve Bone Mass and Strength.

colonization with GM from children (CGM) but not from the elderly (EGM) prevents decreases in bone mass and bone strength in conventionally raised, ovariectomy (OVX)-induced osteoporotic mice.


Akkermansia muciniphila Protects Against Antibiotic-Associated Diarrhea in Mice.

Pasteurized Akk or Amuc_1100 significantly decreased the diarrhea status score and colon injury of AAD model mice.


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

Thirty-three trials involving 1346 participants were included. Overall, ITF supplementation could significantly reduce concentrations of fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), fasting insulin (FINS) and homeostasis model assessment-insulin resistance (HOMA-IR).


Assessing the effects of inulin-type fructan intake on body weight, blood glucose, and lipid profile: A systematic review and meta-analysis of randomized controlled trials.

ITF intake lowers blood glucose, total cholesterol, and TAG in the people with diabetes, and they may benefit from addition of inulin into their diets, but the underlying mechanisms responsible for these effects are inconclusive.


The effects of chicory inulin-type fructans supplementation on weight management outcomes: systematic review, meta-analysis, and meta-regression of randomized controlled trials.

Chicory ITF significantly reduced body weight [mean difference (MD): -0.97 kg; 95% CI: -1.34, -0.59); n = 1184] compared with placebo.


Milk Powder Co-Supplemented with Inulin and Resistant Dextrin Improves Glycemic Control and Insulin Resistance in Elderly Type 2 Diabetes Mellitus: A 12-Week Randomized, Double-Blind, Placebo-Controlled Trial.

For the MPCIR group, systolic blood pressure (BP) and diastolic BP are reduced significantly by 5.45 and 4.56 mm Hg (p < 0.001, vs placebo group), respectively.

favorable-cue: "blood pressure (bp) and diastolic bp are reduced"


Impact of prebiotic supplementation on T-cell subsets and their related cytokines, anthropometric features and blood pressure in patients with type 2 diabetes mellitus: A randomized placebo-controlled Trial.

The present study showed several beneficial effects of oligofructose-enriched inulin on the improvement of the glycemic status, lipid profile, and immune markers in patients with T2DM.


Oligofructose-enriched inulin improves some inflammatory markers and metabolic endotoxemia in women with type 2 diabetes mellitus: a randomized controlled clinical trial.

In women with type 2 diabetes and suboptimal daily dietary fiber intake, oligofructose-enriched inulin may help to modulate some inflammatory markers.


Inulin controls inflammation and metabolic endotoxemia in women with type 2 diabetes mellitus: a randomized-controlled clinical trial.

Inulin-supplemented patients exhibited a significant decrease in FBS (8.5%), HbA1c (10.4%), fasting insulin (34.3%), homeostasis model assessment of insulin resistance (HOMA-IR) (39.5%), hs-CRP (35.6%), TNF-α (23.1%), and LPS (27.9%) compared with the maltodextrin group (p < 0.05).

favorable-cue: "decrease in fbs (8.5%), hba1c"


The effects of sodium butyrate and inulin supplementation on angiotensin signaling pathway via promotion of abundance in type 2 diabetes; A randomized, double-blind, placebo-controlled trial.

Intervention had significant effects on inflammatory and oxidative stress parameters and led to improvement of hypertension. However, further investigations are needed to make concise conclusions.


Prebiotics may reduce serum concentrations of C-reactive protein and ghrelin in overweight and obese adults: a systematic review and meta-analysis.

Meta-analysis showed reduction in serum concentrations of ghrelin (-37.17 pg/mL; 95%CI = -69.62, -4.73; P = 0.025) and CRP (SMD [standardized mean difference] = -0.31; 95%CI = -0.58, -0.04; P = 0.027) after supplementation of inulin-type fructans.


Effectiveness of inulin intake on indicators of chronic constipation; a meta-analysis of controlled randomized clinical trials.

We found a significant overall effect of inulin on stool frequency (DEM = 0.69, 95%CI: 0.04, 1.34), stool consistency (Bristol scale) (DEM = 1.07, 95% CI: 0.70, 1.45), transit time (DEM = -0.57, 95% CI: -0.99, -0.15) and hardness of stool (RR = 0.42, 95% CI: 0.26, 0.70). Pain and bloating do not improve with inulin intake.


Effect of consumption of chicory inulin on bowel function in healthy subjects with constipation: a randomized, double-blind, placebo-controlled trial.

Consumption of OraftiInulin significantly increased stool frequency compared to placebo (median 4.0 [IQR 2.5-4.5] versus 3.0 [IQR 2.5-4.0] stools/week, p = 0.038).


Microbiota benefits after inulin and partially hydrolized guar gum supplementation: a randomized clinical trial in constipated women.

Consumption of I-PHGG produced clinical results comparable to placebo in constipated females, but had additional protective effects on gut microbiota by decreasing the amount of pathological bacteria of the Clostridium genera.

no-difference-cue: "comparable to placebo" | favorable-cue: "protective"


Inulin-type fructans improve active ulcerative colitis associated with microbiota changes and increased short-chain fatty acids levels.

Fructans significantly reduced colitis in the high-dose group, with 77% of patients showing a clinical response versus 33% in the low-dose group


Prebiotics in irritable bowel syndrome and other functional bowel disorders in adults: a systematic review and meta-analysis of randomized controlled trials.

Prebiotics do not improve gastrointestinal symptoms or QoL in patients with IBS or other FBDs, but they do increase bifidobacteria. Variations in prebiotic type and dose impacted symptom improvement or exacerbation.


A combination of prebiotic short- and long-chain inulin-type fructans enhances calcium absorption and bone mineralization in young adolescents.

Calcium absorption was significantly greater in the fructan group than in the control group at 8 wk (difference: 8.5 +/- 1.6%; P < 0.001) and at 1 y (difference: 5.9 +/- 2.8%; P = 0.04).


Inulin-type fructans and bone health: state of the art and perspectives in the management of osteoporosis.

given in combination with isoflavones, they may have a potential for maintaining or improving the bone mass of human subjects, by modulating the bioavailability of phyto-oestrogens.


The efficacy of daily snack replacement with oligofructose-enriched granola bars in overweight and obese adults: a 12-week randomised controlled trial.

replacing daily snacks for 12 weeks with oligofructose-supplemented granola bars does not differentially affect energy intake, body weight and body composition compared with a control bar. However, there was an indication that appetite was lower after oligofructose bar consumption.


Effects of β-glucan and inulin consumption on postprandial appetite, energy intake and food consumption in healthy females: A randomized controlled trial.

Both dietary fibres significantly reduced the VAS scores of hunger, prospective food consumption and desire to eat, and increased satiety compared with the control group.


The Nitrate-Independent Blood Pressure-Lowering Effect of Beetroot Juice: A Systematic Review and Meta-Analysis.

Overall, SBP (-3.55 mm Hg; 95% CI: -4.55, -2.54 mm Hg) and DBP (-1.32 mm Hg; 95% CI: -1.97, -0.68 mm Hg) were significantly lower in the beetroot juice-supplemented groups than in the control groups.


Medium-term effects of dietary nitrate supplementation on systolic and diastolic blood pressure in adults: a systematic review and meta-analysis.

However, the effect was only significant when measured in resting clinical settings as no significant changes in BP were observed using 24-h ambulatory and daily home monitorings.

no-difference-cue: "no significant changes"


Ageing modifies the effects of beetroot juice supplementation on 24-hour blood pressure variability: An individual participant meta-analysis.

The pooled effect of beetroot juice on all BP outcomes was not significant. Beetroot juice ingestion determined a significant decrease in nocturnal systolic BP variability in subjects aged less than 65 y (2.8 mmHg, -4.5 -1.0, p = 0.002)

favorable-cue: "decrease in nocturnal systolic"


Efficacy of dietary nitrate-rich beetroot juice supplementation in patients with chronic obstructive pulmonary disease (COPD): A systematic review and meta-analysis.

A pooled analysis from eight included trials showed no significant difference between dietary nitrate-rich beetroot juice and placebo in systolic blood pressure, diastolic blood pressure, heart rate, 6-min walk test, cycling ergometry endurance time, and maximum rate of oxygen consumption (VO).

no-difference-cue: "no significant difference"


Effectiveness of dietary inorganic nitrate for lowering blood pressure in hypertensive adults: a systematic review.

There is insufficient evidence to support or refute the use of inorganic nitrate for any effect on blood pressure at this time.


Beetroot juice and exercise: pharmacodynamic and dose-response relationships.

However, 140 and 280 ml BR reduced the steady-state oxygen (O2) uptake during moderate-intensity exercise by 1.7% (P = 0.06) and 3.0% (P < 0.05), whereas time-to-task failure was extended by 14% and 12% (both P < 0.05), respectively, compared with PL.


Beetroot Juice Supplementation Improves High-Intensity Intermittent Type Exercise Performance in Trained Soccer Players.

Six days of BR ingestion effectively improves high-intensity intermittent type exercise performance in trained soccer players.


Flavonoid-rich apples and nitrate-rich spinach augment nitric oxide status and improve endothelial function in healthy men and women: a randomized controlled trial.

Compared to control, all treatments resulted in higher flow-mediated dilatation (P<0.05) and lower pulse pressure (P<0.05), and apple and spinach resulted in lower systolic blood pressure (P<0.05).


Dietary nitrate modulates cerebral blood flow parameters and cognitive performance in humans: A double-blind, placebo-controlled, crossover investigation.

Dietary nitrate modulated the hemodynamic response to task performance, with an initial increase in CBF at the start of the task period, followed by consistent reductions during the least demanding of the three tasks utilised. Cognitive performance was improved on the serial 3s subtraction task.


Incremental Doses of Nitrate-Rich Beetroot Juice Do Not Modify Cognitive Function and Cerebral Blood Flow in Overweight and Obese Older Adults: A 13-Week Pilot Randomised Clinical Trial.

The findings of this pilot study showed that cognitive function and CBF were not affected by supplementation with NO-rich beetroot juice for 13 weeks


Performance and Health Benefits of Dietary Nitrate Supplementation in Older Adults: A Systematic Review.

Six studies reported improvements in CV health (blood pressure and blood flow), while six found no improvement.

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


Effects of short-term dietary nitrate supplementation on blood pressure, O2 uptake kinetics, and muscle and cognitive function in older adults.

Dietary nitrate supplementation reduced resting blood pressure and improved Vo(2) kinetics during treadmill walking in healthy older adults but did not improve walking or cognitive performance.

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


Acute dietary nitrate supplementation enhances compensatory vasodilation during hypoxic exercise in older adults.

Following BR consumption, compensatory vasodilation did not change in young (13.7 ± 3.3%, P = 0.81) adults but was substantially augmented in older adults (11.4 ± 2.1%, P < 0.01).


Acute effect of dietary nitrate on forearm muscle oxygenation, blood volume and strength in older adults: A randomized clinical trial.

In summary, a single dose of a beetroot-based gel speeds up muscle O2 resaturation, increases blood volume and improves recovery of handgrip strength after handgrip exercise in older adults.


Short-term beetroot juice supplementation improves muscle speed and power but does not reduce blood pressure or oxidative stress in 65-79 y old men and women.

This was accompanied by 5 ± 11% and 7 ± 13% increases in maximal knee extensor speed (Vmax) and power (Pmax), respectively.


Effects of Palmitoylethanolamide (PEA) on Nociceptive, Musculoskeletal and Neuropathic Pain: Systematic Review and Meta-Analysis of Clinical Evidence.

However, the results are downgraded due to the high heterogeneity of the studies (I2 = 99%), and the funnel plot suggests publication bias.


Micronized palmitoylethanolamide/trans-polydatin treatment of endometriosis-related pain: a meta-analysis.

the administration of micronized palmitoylethanolamide/trans-polydatin (400 mg/40 mg) twice a day for three months provided a clinically relevant improvement of chronic pelvic pain and dysmenorrhea while improving deep dyspareunia to a limited degree.


A double-blind randomized placebo controlled study assessing safety, tolerability and efficacy of palmitoylethanolamide for symptoms of knee osteoarthritis.

The study demonstrated that palmitoylethanolamide may be a novel treatment for attenuating pain and reducing other associated symptoms of knee osteoarthritis.


Oral Palmitoylethanolamide Treatment Is Associated with Reduced Cutaneous Adverse Effects of Interferon-beta1a and Circulating Proinflammatory Cytokines in Relapsing-Remitting Multiple Sclerosis.

Patients with MS receiving um-PEA perceived an improvement in pain sensation without a reduction of the erythema at the injection site. A significant improvement in QoL was observed.


Palmitoylethanolamide versus a nonsteroidal anti-inflammatory drug in the treatment of temporomandibular joint inflammatory pain.

These data suggest that PEA is effective in treating TMJ inflammatory pain.


Effectiveness of the association micronized N-Palmitoylethanolamine (PEA)-transpolydatin in the treatment of chronic pelvic pain related to endometriosis after laparoscopic assessment: a pilot study.

A marked decrease in dysmenorrhoea, dyspareunia and pelvic pain was observed in all groups, and the association between N-Palmitoylethanolamine and transpolydatin resulted to be more effective than placebo (P<.001).


N-of-1 Randomized Trials of Ultra-Micronized Palmitoylethanolamide in Older Patients with Chronic Pain.

A small statistically significant effect in favor of um-PEA was seen at the mixed method analyses in two patients (effect size equal to 8% of the baseline pain).


Micronized palmitoylethanolamide reduces the symptoms of neuropathic pain in diabetic patients.

Statistical analysis (ANOVA) indicated a highly significant reduction in pain severity (P < 0.0001) and related symptoms (P < 0.0001) evaluated by Michigan Neuropathy Screening instrument, Total Symptom Score, and Neuropathic Pain Symptoms Inventory.


Palmitoylethanolamide in Fibromyalgia: Results from Prospective and Retrospective Observational Studies.

PEA introduction after 3 months of therapeutic regimen with DLX + PGB provided a significant improvement in pain symptoms, with a further reduction in the number of TPs and significant reduction in pain, compared to combined DLX + PGB only (p < 0.0001 for TPs and Visual Analog Scale comparisons).


Palmitoylethanolamide, a naturally occurring disease-modifying agent in neuropathic pain.

palmitoylethanolamide, a member of the N-acylethanolamine family which is produced from the lipid bilayer on-demand, is capable of exerting anti-allodynic and anti-hyperalgesic effects by down-modulating both microglial and mast cell activity


Palmitoylethanolamide dampens neuroinflammation and anxiety-like behavior in obese mice.

PEA directly counteracted inflammation and mitochondrial dysfunction in a PPAR-alpha-dependent manner since the pharmacological blockade of the receptor reverted its effects.


N-palmitoylethanolamide Prevents Parkinsonian Phenotypes in Aged Mice.

These findings propose this strategy as a valid approach to prevent neurodegenerative diseases associated with old age.


Prophylactic Palmitoylethanolamide Prolongs Survival and Decreases Detrimental Inflammation in Aged Mice With Bacterial Meningitis.

Our findings suggest that prophylactic PEA can counteract infection associated detrimental responses in old animals. Accordingly, PEA treatment slowed the onset of infection symptoms and prolonged the survival of old infected mice.

unfavorable-cue: "detrimental" | favorable-cue: "slowed"


Efficacy evaluation of standardized Boswellia serrata extract (Aflapin) in osteoarthritis: A systematic review and sub-group meta-analysis study.

BS supplementation significantly reduced VAS (MD: -10.71; p<0.00001), LFI (MD: -2.99; p<0.00001), WOMAC-pain (MD: -10.69; p<0.0001), WOMAC-stiffness (MD: -5.49; p<0.00001), and WOMAC-function (MD: -10.69; p<0.00001) scores compared to control therapy.


Efficacy of curcumin and Boswellia for knee osteoarthritis: Systematic review and meta-analysis.

Both curcuminoid and boswellia formulations were statistically significantly more effective than placebo for pain relief and functional improvement.


Frankincense: systematic review.

The evidence for the effectiveness of B serrata extracts is encouraging but not compelling.


Efficacy and Safety of Aflapin, a Novel Boswellia serrata Extract, in the Treatment of Osteoarthritis of the Knee: A Short-Term 30-Day Randomized, Double-Blind, Placebo-Controlled Clinical Study.

Post-trial, VAS, LFI, WOMAC pain, WOMAC stiffness, WOMAC function, and total WOMAC scores decreased in the Aflapin group by 45%, 40.9%, 44.4%, 66.3%, 44.4%, and 48%, respectively.


A Standardized Boswellia serrata Extract Improves Knee Joint Function and Cartilage Morphology in Human Volunteers with Mild to Moderate Osteoarthritis in a Randomized Placebo-Controlled Study.

SN13108F supplementation is safe, and it mitigates joint pain and improves musculoskeletal function and cartilage morphology in KOA.


Efficacy and Safety of Boswellia serrata and Apium graveolens L. Extract Against Knee Osteoarthritis and Cartilage Degeneration: A Randomized, Double-blind, Multicenter, Placebo-Controlled Clinical Trial.

Oral administration of the nutraceutical resulted in prolonged symptomatic relief with reduced pain, stiffness, and swelling.


Effect of a combination of C. longa and B. serrata extracts on hand osteoarthritis. Results of a double-blind, randomized, placebo-controlled, multicenter trial.

CBTIL relieves pain in patients with hand osteoarthritis. Together with its safety, this clinically relevant symptomatic effect suggests that CBTIL may be an alternative to oral NSAIDs and analgesics for managing symptomatic hand osteoarthritis.


Evaluation of the effect of Elaeagnus angustifolia alone and combined with Boswellia thurifera compared with ibuprofen in patients with knee osteoarthritis: a randomized double-blind controlled clinical trial.

Consumption of E. angustifolia fruit extract either alone or in combination with Boswellia oleo-gum resin extract could decrease pain and improve function in patients with knee osteoarthritis comparable to ibuprofen.


Efficacy and tolerability of Boswellia serrata extract in treatment of osteoarthritis of knee--a randomized double blind placebo controlled trial.

All patients receiving drug treatment reported decrease in knee pain, increased knee flexion and increased walking distance. The frequency of swelling in the knee joint was decreased.


Boswellic acids in chronic inflammatory diseases.

The mechanism of this action is due to some boswellic acids. It is different from that of NSAID and is related to components of the immune system. The most evident action is the inhibition of 5-lipoxygenase.


Boswellic acids: biological actions and molecular targets.

Approaches in order to elucidate the molecular mechanisms underlying the biological effects of BAs identified 5-lipoxygenase, human leukocyte elastase, toposiomerase I and II, as well as IkappaB kinases as molecular targets of BAs.


Boswellia serrata: an overall assessment of in vitro, preclinical, pharmacokinetic and clinical data.

boswellic acids failed to inhibit leukotriene formation in human whole blood, and pharmacokinetic data revealed very low concentrations of AKBA and KBA in plasma, being far below the effective concentrations for bioactivity in vitro.


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

Glu, MSM and their combination significantly improved signs and symptoms of osteoarthritis compared with placebo.


Systematic review of the nutritional supplements dimethyl sulfoxide (DMSO) and methylsulfonylmethane (MSM) in the treatment of osteoarthritis.

The data from the more rigorous MSM trials provide positive but not definitive evidence that MSM is superior to placebo in the treatment of mild to moderate OA of the knee.


Effects of dietary supplements on patients with osteoarthritis: A systematic review and network meta-analysis.

In the WOMAC pain score, the SUCRA of passion fruit peel extract was 91% (mean difference [MD]: -9.2; 95% confidence interval [CI]: [-16.0, -2.3]), followed by methylsulfonylmethane (89%)


A randomized controlled trial evaluating methylsulfonylmethane versus placebo to prevent knee pain in military initial entry trainees.

Three grams of MSM administered daily did not provide significant improvements in the 5 KOOS subscales or the 6 POMS subscales at 30 days or 60 days.


Dietary Ingredients as an Alternative Approach for Mitigating Chronic Musculoskeletal Pain: Evidence-Based Recommendations for Practice and Research in the Military.

Recommendations were made against the use of collagen, creatine, devil's claw, l-carnitine, methylsulfonylmethane, pycnogenol, willow bark extract, and vitamin E.


Efficacy and safety of a supplement combination on hand pain among people with symptomatic hand osteoarthritis an internet-based, randomised clinical trial the RADIANT study.

There were no significant differences in symptomatic relief between the two groups over 12 weeks. These findings do not support the use of the supplement combination for treating hand pain in people with HOA.

no-difference-cue: "no significant differences"


The "MESACA" study: methylsulfonylmethane and boswellic acids in the treatment of gonarthrosis.

Although the combined administration of MSM and BA in the treatment of gonarthrosis was not shown to be more efficacious than placebo in the management of the clinical and functional picture, it significantly reduced patients need for anti-inflammatory drugs.


Effects of Methylsulfonylmethane (MSM) on exercise-induced oxidative stress, muscle damage, and pain following a half-marathon: a double-blind, randomized, placebo-controlled trial.

MSM supplementation attenuated post-exercise muscle and joint pain at clinically, but not statistically significant levels.


Influence of methylsulfonylmethane on markers of exercise recovery and performance in healthy men: a pilot study.

MSM, especially when provided at 3.0 grams per day, may favorably influence selected markers of exercise recovery.


Methylsulfonylmethane inhibits NLRP3 inflammasome activation.

MSM significantly attenuated NLRP3 inflammasome activation in lipopolysaccharide-primed macrophages, although it had no effect on NLCR4 or AIM2 inflammasome activation.


Methylsulfonylmethane: Applications and Safety of a Novel Dietary Supplement.

As a Generally Recognized As Safe (GRAS) approved substance, MSM is well-tolerated by most individuals at dosages of up to four grams daily, with few known and mild side effects.


Methylsulfonylmethane for treatment of low back pain: A safety analysis of a randomized, controlled trial.

MSM has no effects on WBC, platelets, Hb, total bilirubin, AST, ALT, creatinine weight, DBP, or SBP in this study.


A multicentered, open-label trial on the safety and efficacy of methylsulfonylmethane in the treatment of seasonal allergic rhinitis.

Day 7 upper and total respiratory symptoms were reduced significantly from baseline (p < 0.01 and p < 0.005, respectively).


Self-Administered Acupressure for Probable Knee Osteoarthritis in Middle-Aged and Older Adults: A Randomized Clinical Trial.

In this randomized clinical trial, SAA with a brief KHE program was efficacious and cost-effective in relieving knee pain and improving mobility in middle-aged and older adults with probable knee OA.


Self-Acupressure for Older Adults With Symptomatic Knee Osteoarthritis: A Randomized Controlled Trial.

Self-administered acupressure is superior to usual care in pain and physical function improvement for older adults with knee OA. The reason for the benefits is unclear, and the placebo effect may play a role.


Acupressure effect on sleep quality: A systematic review and meta-analysis.

Comparison with the sham group (7 trials with 385 patients) yielded low heterogeneity and an overall effect of 13%-19% improvement in the PSQI score (MD = -3.41, 95% CI -4.08, -2.75; I = 12%).


Efficacy of Auricular Acupressure for Chronic Low Back Pain: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

The encouraging evidence of this study indicates that it is recommended to provide auricular acupressure to patients with chronic low back pain.


Effect of acupressure on postpartum low back pain, salivary cortisol, physical limitations, and depression: a randomized controlled pilot study.

Participants in the intervention group had significantly lower levels of LBP intensity, daily activity limitations, physical activity limitations, and postpartum depression than those in the control group.


Clinical Evidence for Association of Acupuncture and Acupressure With Improved Cancer Pain: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis found that acupuncture and/or acupressure was significantly associated with reduced cancer pain and decreased use of analgesics, although the evidence level was moderate.


Acupressure for Cancer-Related Fatigue in Elderly Cancer Patients: A Randomized Controlled Study.

Acupressure can be recommended as an integrative treatment for cancer-related fatigue because it is effective, easy to use, tolerable and does not cause serious side effects.


Management of Fatigue in Adult Survivors of Cancer: ASCO-Society for Integrative Oncology Guideline Update.

yoga, acupressure, and moxibustion helped to manage CRF after completion of treatment.


Effects of Acupressure on Anxiety: A Systematic Review and Meta-Analysis.

Our meta-analysis suggests that acupressure can alleviate anxiety.


Effects of acupressure on anxiety: a systematic review and meta-analysis.

Acupressure seems to be effective in providing immediate relief of pretreatment anxiety among adults, and has a medium effect size.


Mindfulness-based stress reduction with acupressure for sleep quality in breast cancer patients with insomnia undergoing chemotherapy: A randomized controlled trial.

Acupressure and combined therapy outperformed MBSR in improving sleep quality.


Acupuncture for insomnia.

Due to poor methodological quality, high levels of heterogeneity and publication bias, the current evidence is not sufficiently rigorous to support or refute acupuncture for treating insomnia.


The effectiveness of auricular acupressure on pain management during labor: A systematic review and meta-analysis of randomized controlled trials.

Effective labor pain relief, better labor pain perception, and the lack of adverse effects support the use of auricular acupressure.


Regular use of acupressure mats reduces perceived stress at subjective but not psychophysiological levels: Insights from a three-week relaxation training.

training with an acupressure mat yielded no superior effects compared with an active control condition in healthy young students.


Lithium deficiency and the onset of Alzheimer's disease.

Replacement therapy with lithium orotate, which is a Li salt with reduced amyloid binding, prevents pathological changes and memory loss in AD mouse models and ageing wild-type mice.


Lithium in the prevention of suicide in mood disorders: updated systematic review and meta-analysis.

Lithium was more effective than placebo in reducing the number of suicides (odds ratio 0.13, 95% confidence interval 0.03 to 0.66) and deaths from any cause (0.38, 0.15 to 0.95).


Lithium as a Treatment for Alzheimer's Disease: A Systematic Review and Meta-Analysis.

Lithium significantly decreased cognitive decline as compared to placebo (standardized mean difference = -0.41, 95% confidence interval = -0.81 to -0.02, p = 0.04, I2 = 47% , 3 studies, n = 199).


Comparative efficacy, tolerability and acceptability of donanemab, lecanemab, aducanumab and lithium on cognitive function in mild cognitive impairment and Alzheimer's disease: A systematic review and network meta-analysis.

On the Mini-Mental State Examination, lithium significantly outperformed donanemab, aducanumab and placebo. On the Alzheimer's Disease Assessment Scale-cognitive subscale, the efficacy of all active drugs was significantly higher than placebo.


Relationship between suicide mortality and lithium in drinking water: A systematic review and meta-analysis.

A significant relationship was found between the lithium concentration in drinking water and reduced suicide mortality (OR= 0.42; 95% CI: 0.27-0.67; p-value <0.01).

favorable-cue: "reduced suicide mortality"


Disease-modifying properties of long-term lithium treatment for amnestic mild cognitive impairment: randomised controlled trial.

The present data support the notion that lithium has disease-modifying properties with potential clinical implications in the prevention of Alzheimer's disease.


Clinical and biological effects of long-term lithium treatment in older adults with amnestic mild cognitive impairment: randomised clinical trial.

Participants in the placebo group displayed cognitive and functional decline, whereas lithium-treated patients remained stable over 2 years.


Microdose lithium treatment stabilized cognitive impairment in patients with Alzheimer's disease.

This data suggests the efficacy of a microdose lithium treatment in preventing cognitive loss, reinforcing its therapeutic potential to treat AD using very low doses.


Revisiting global cognitive and functional state 13 years after a clinical trial of lithium for mild cognitive impairment.

This data set suggests that older adults with amnestic MCI who had been treated with lithium during a previous randomized controlled trial had a better long-term global cognitive outcome than those from a matched sample who did not receive the intervention.


Low Dose Lithium Treatment of Behavioral Complications in Alzheimer's Disease: Lit-AD Randomized Clinical Trial.

Low-dose lithium was not efficacious in treating agitation but was associated with global clinical improvement and excellent safety.


Association of Lithium in Drinking Water With the Incidence of Dementia.

Long-term increased lithium exposure in drinking water may be associated with a lower incidence of dementia in a nonlinear way; however, confounding from other factors associated with municipality of residence cannot be excluded.

favorable-cue: "associated with a lower"


Lithium treatment and risk of dementia.

Persons who purchased lithium at least once had an increased rate of dementia compared with persons not exposed to lithium (relative risk, 1.47; 95% confidence interval, 1.22-1.76). For persons who continued to take lithium, the rate of dementia decreased to the same level as the rate for the general population.


Association Between Lithium Use and Risk of Alzheimer's Disease.

when we restricted the analyses to patients with bipolar disorder to minimize potential confounding by indication, lithium was not associated with Alzheimer's disease risk (aOR = 1.36; 95% CI, 0.89-2.09), and there were no apparent trends of greater risk with increasing duration or dose.


Lithium in drinking water and suicide mortality.

In replicating and extending previous results, this study provides strong evidence that geographic regions with higher natural lithium concentrations in drinking water are associated with lower suicide mortality rates.


Lithium in Public Drinking Water and Suicide Mortality in Portugal: Initial Approach.

Unlike most international studies regarding natural lithium levels and suicide risk, no inverse relation was found in Portugal.


Lithium Promotes Longevity through GSK3/NRF2-Dependent Hormesis.

We demonstrate that lithium extends lifespan in female and male Drosophila, when administered throughout adulthood or only later in life.


Neuroprotective effects of lithium: implications for the treatment of Alzheimer's disease and related neurodegenerative disorders.

The putative neuroprotective effects of lithium rely on the fact that it modulates several homeostatic mechanisms involved in neurotrophic response, autophagy, oxidative stress, inflammation, and mitochondrial function.


Cognitive enhancement of healthy older adults using hyperbaric oxygen: a randomized controlled trial.

There was a significant group-by-time interaction in global cognitive function post-HBOT compared to control (p=0.0017). The most striking improvements were in attention (net effect size=0.745) and information processing speed (net effect size=0.788).


The effect of hyperbaric oxygen therapy on the pathophysiology of skin aging: a prospective clinical trial.

The study indicates, for the first time in humans, that HBOT can significantly modulate the pathophysiology of the skin aging in a healthy aging population. The demonstrated mechanisms include angiogenesis and senescent cell clearance.


Hyperbaric oxygen therapy: future prospects in regenerative therapy and anti-aging.

HBOT affects physiological processes at the genetic level by altering gene expression, delaying cell senescence, and assisting in telomere length enhancement.


Rejuvenation Through Oxygen, More or Less.

In a recent report, a small clinical trial employing 60 sessions of intermittent hyperbaric oxygen therapy (HBOT) studying old humans resulted in increased mean telomere length of immune cells including B cells, natural killer cells, T helper, and cytotoxic T lymphocytes.

favorable-cue: "increased mean telomere"


Hyperbaric oxygen therapy can diminish fibromyalgia syndrome--prospective clinical trial.

HBOT in both groups led to significant amelioration of all FMS symptoms, with significant improvement in life quality.


Hyperbaric oxygen induces late neuroplasticity in post stroke patients--randomized, prospective trial.

The results indicate that HBOT can lead to significant neurological improvements in post stroke patients even at chronic late stages.


Efficacy of hyperbaric oxygen therapy for diabetic foot ulcers: An updated systematic review and meta-analysis.

Hyperbaric oxygen therapy increased the healing rate of diabetic foot ulcers (relative risk, 1.901; 95% CI = 1.484-2.435, p < 0.0001), shortened the healing time (MD = -19.360; 95% CI = -28.753~-9.966, p < 0.001), and reduced the incidence of major amputation (relative risk, 0.518, 95% CI = 0.323-0.830, P < 0.01).


The role of hyperbaric oxygen therapy in the treatment of diabetic foot ulcers: a systematic review with meta-analysis of randomized controlled trials on limb amputation and ulcer healing.

The present review offers evidence that adjuvant HBOT decreases risk of major amputation while promoting wound healing when combined to standard treatment in the management of DFU.


Hyperbaric Oxygen Therapy for Patients With Sudden Sensorineural Hearing Loss: A Systematic Review and Meta-analysis.

In this systematic review and meta-analysis, HBOT as part of a combination treatment was significantly associated with improved hearing outcomes in patients with SSNHL over control treatments.


Hyperbaric oxygen therapy for late radiation tissue injury.

HBOT also carries a risk of adverse events, including an increased risk of a reduction in visual acuity (usually temporary) and of ear barotrauma on compression.


Effects of Hyperbaric Oxygen Therapy on Long COVID: A Systematic Review.

Most studies found that HBOT can improve quality of life, fatigue, cognition, neuropsychiatric symptoms, and cardiopulmonary function. Although HBOT has shown some benefits for long COVID symptoms, further rigorous large-scale RCTs are required to establish precise indications, protocols, and post-treatment evaluations.


Interventions for the management of long covid (post-covid condition): living systematic review.

No compelling evidence was found to support the effectiveness of other interventions, including, among others, vortioxetine, leronlimab, combined probiotics-prebiotics, coenzyme Q10, amygdala and insula retraining, combined L-arginine and vitamin C, inspiratory muscle training, transcranial direct current stimulation, hyperbaric oxygen


Relative efficacy and safety of topical non-steroidal anti-inflammatory drugs for osteoarthritis: a systematic review and network meta-analysis of randomised controlled trials and observational studies.

Of all topical NSAIDs, diclofenac patches were most effective for OA pain (SMD=-0.81, 95% CI -1.12 to -0.52) and piroxicam was most effective for functional improvement (SMD=-1.04, 95% CI -1.60 to -0.48) compared with placebo.


Topical Diclofenac Solution for Osteoarthritis of the Knee: An Updated Meta-Analysis of Randomized Controlled Trials.

In comparison to the vehicle control, the mean differences for WOMAC pain, stiffness, and physical function subscales, as well as pain on walking, were all statistically significant in favor of topical diclofenac solution.


Randomized controlled trial of diclofenac sodium gel in knee osteoarthritis.

At week 12, the DSG group had significant decreases versus the vehicle group in mean WOMAC pain (P = 0.01), mean WOMAC physical function (P = 0.001), and mean global rating of disease (P < 0.001).


Diclofenac sodium gel in patients with primary hand osteoarthritis: a randomized, double-blind, placebo-controlled trial.

Diclofenac sodium gel decreased pain intensity scores by 42%-45%, total AUSCAN scores by 35%-40%, and global rating of disease by 36%-40%.


Efficacy and safety of diclofenac sodium 2% topical solution for osteoarthritis of the knee: a randomized, double-blind, vehicle-controlled, 4 week study.

Significantly greater reductions in least-squares mean (standard error) WOMAC pain scores were observed for diclofenac-treated (-4.4 [0.4]) versus vehicle-treated patients (-3.4 [0.4]) at the final visit (p = 0.040).


Topical diclofenac patch in patients with knee osteoarthritis: a randomized, double-blind, controlled clinical trial.

The active treatment group showed a significant improvement in pain, Lequesne's Index, and the physician's and patient's global assessment of efficacy.


Efficacy of topical diclofenac diethylamine gel in osteoarthritis of the knee.

On the primary outcome, average pain on movement over Days 1-14, diclofenac gel was significantly superior to placebo gel.


Systematic review of topical diclofenac for the treatment of acute and chronic musculoskeletal pain.

The effectiveness of topical diclofenac was also demonstrated in chronic musculoskeletal pain but with a higher NNT (worse) compared with acute pain.


Management of Acute Pain From Non-Low Back, Musculoskeletal Injuries : A Systematic Review and Network Meta-analysis of Randomized Trials.

Topical NSAIDs, followed by oral NSAIDs and acetaminophen with or without diclofenac, showed the most convincing and attractive benefit-harm ratio for patients with acute pain from non-low back, musculoskeletal injuries.


Topical diclofenac therapy for osteoarthritis: a meta-analysis of randomized controlled trials.

Topical diclofenac appears to be effective in both pain relief (standard mean differences (SMD) = 0.40; 95 % confidence interval (CI) 0.19 to 0.62; P = 0.0003) and function improvement (SMD = 0.23; 95 % CI 0.03 to 0.43; P = 0.03) when compared with the control group.


Topical analgesics for acute and chronic pain in adults - an overview of Cochrane Reviews.

Topical Diclofenac (NSAID Gel);Topical Lidocaine;Topical Methyl Salicylate + Menthol (Medicated Patch)

In chronic musculoskeletal conditions with assessments over 6 to 12 weeks, topical diclofenac and ketoprofen had limited efficacy in hand and knee osteoarthritis, as did topical high-concentration capsaicin in postherpetic neuralgia.


Efficacy and safety of topical NSAIDs in the management of osteoarthritis: Evidence from real-life setting trials and surveys.

In real-life studies, topical and oral NSAIDs demonstrate an equivalent effect on knee pain over 1 year of treatment, with fewer adverse events due to lower systemic absorption of topical NSAIDs compared with oral NSAIDs.


Comparison of the Efficacy and Safety of Ketoprofen Plaster and Diclofenac Plaster for Osteoarthritis-Related Knee Pain: A Multicenter, Randomized, Active-Controlled, Open-Label, Parallel-Group, Phase III Clinical Trial.

After 3 weeks of treatment, the least squares mean change from baseline in knee pain intensity scores during walking was -35.9 (95% CI, -39.7 to -32.2) in the ketoprofen group and -31.7 (95% CI, -35.5 to -27.9) in the diclofenac group, with noninferiority found (least squares mean difference, -4.2; 95% CI, -9.6 to 1.1).


The use of topical diclofenac for pain in osteoarthritis of the knee: a review.

Findings imply that topical diclofenac sodium is an efficacious and safe method of pain control in patients with OA of the knee.


Capsaicin for osteoarthritis pain.

Capsaicin treatment efficacy (vs. placebo) for change in VAS pain score was moderate, at 0.44 (95% CI 0.25-0.62) over 4 weeks of treatment.


Systematic review of topical capsaicin for the treatment of chronic pain.

The relative benefit from topical capsaicin 0.025% or plaster compared with placebo was 1.5 (1.1 to 2.0) and the number needed to treat was 8.1 (4.6 to 34).


The relative efficacy of topical non-steroidal anti-inflammatory drugs and capsaicin in osteoarthritis: a network meta-analysis of randomised controlled trials.

Current evidence indicates that topical NSAIDs and capsaicin in licensed doses may be equally effective for pain relief in OA.


Efficacy of symptomatic control of knee osteoarthritis with 0.0125% of capsaicin versus placebo.

The respective mean difference of VAS and total WOMAC score in the capsaicin group vs. the placebo group was statistically significant (p < 0.05).


The analgesic efficacy of topical capsaicin is enhanced by glyceryl trinitrate in painful osteoarthritis: a randomized, double blind, placebo controlled study.

The study showed that topical capsaicin and glyceryl trinitrate have an analgesic effect in painful osteoarthritis.


Civamide cream 0.075% in patients with osteoarthritis of the knee: a 12-week randomized controlled clinical trial with a longterm extension.

Significance in favor of civamide cream 0.075% was achieved for the TWA for all 3 co-primary efficacy variables: WOMAC pain (p = 0.009), WOMAC physical function (p < 0.001), and SGE (p = 0.008).


Capsicum pain plaster in chronic non-specific low back pain.

The study unequivocally achieved the target criterion with a rate of responders in the capsicum group of 60.8% against 42.1% in the placebo group (p = 0.0219).


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

a weak recommendation for use and proposal as second line for lidocaine patches, capsaicin high-concentration patches, and tramadol


The Effectiveness and Safety of Topical Capsaicin in Postherpetic Neuralgia: A Systematic Review and Meta-analysis.

This demonstrated high efficacy of topical capsaicin application and implies that capsaicin could result in pain reduction.


The efficacy of topical 8% capsaicin patches for the treatment of postsurgical neuropathic pain: a systematic review.

The random-effects pooled-analysis denotes an overall Cohen's d of 1.09 (95% CI: 0.58-1.56; < 0.001).


Evidence of effectiveness of herbal medicinal products in the treatment of arthritis. Part I: Osteoarthritis.

meta-analysis was restricted to data from studies of three HMPs: topical capsaicin, avocado-soybean unsaponifiables, and the Chinese herbal mixture SKI306X showed benefit in the alleviation of osteoarthritic pain.


The Treatment of Topical Drugs for Postherpetic Neuralgia: A Network Meta-Analysis.

Lidocaine, high-concentration capsaicin, and aspirin/diethyl ether (ADE) had a higher possibility of bringing pain relief than placebo.


Systematic review and network meta-analysis of the efficacy and safety of lidocaine 700 mg medicated plaster vs. pregabalin.

LMP was found to be similar to pregabalin in reducing pain in all populations but had a better adverse events profile.


Pharmacotherapy and non-invasive neuromodulation for neuropathic pain: a systematic review and meta-analysis.

a weak recommendation for capsaicin 8% patches, capsaicin cream, and lidocaine 5% plasters as second-line recommendation


EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision.

with level A evidence in support of tricyclic antidepressants (TCA), pregabalin, gabapentin, tramadol and opioids (in various conditions), duloxetine, venlafaxine, topical lidocaine and capsaicin patches (in restricted conditions).


Topical Lidocaine for Chronic Pain Treatment.

Topical lidocaine has been approved by health authorities for the treatment of post-herpetic neuralgia in a number of countries, and studies present some degree of evidence of its efficacy and safety in postsurgical pain, diabetic peripheral neuropathy, carpal tunnel syndrome, chronic lower back pain and osteoarthritis.


Topical pain management with the 5% lidocaine medicated plaster--a review.

The risk of systemic adverse events and pharmacokinetic interactions with concomitant medication is minimal owing to low systemic exposure.


Lidocaine 5% medicated plaster: a review of its use in postherpetic neuralgia.

The lidocaine 5% medicated plaster has a direct local action with low systemic exposure and is effective in the treatment of patients with PHN.


5% Lidocaine Medicated Plaster for the Treatment of Postherpetic Neuralgia: A Review of the Clinical Safety and Tolerability.

The 5% lidocaine medicated plaster demonstrated good short- and long-term tolerability with low systemic uptake (3 ± 2%) and minimal risk for systemic adverse drug reactions (ADRs).


5% lidocaine medicated plaster in elderly patients with postherpetic neuralgia: results of a compassionate use programme in France.

Lidocaine plaster treatment resulted in a significant mean reduction of one concomitant PHN treatment per patient in the overall efficacy population analysed at the end of the observation (p < 0.001).


Lidocaine 5%-medicated plaster (Versatis) for localised neuropathic pain: results of a multicentre evaluation of use in children and adolescents.

Benefit was recorded for 79 patients (69%); 32 patients were recorded as receiving no benefit and data were unavailable for 4 patients, and 7 patients reported minor skin reactions.

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


Topical lidocaine patch therapy for myofascial pain.

Mean improvements for average pain intensity (7, 14, and 28 days), general activity (7 and 28 days), mood and sleep (7, 14, and 28 days), walking (14 and 28 days), and ability to work, relationships, and enjoyment of life (28 days) were significant (P < 0.05).


Conclusions: chronic pain studies of lidocaine patch 5% using the Neuropathic Pain Scale.

Significant reduction in the intensity of commonly reported pain qualities in patients with neuropathic and non-neuropathic chronic pain due to low-back pain, osteoarthritis, post-herpetic neuralgia, and painful diabetic neuropathy were achieved.


Topical therapies in the management of chronic pain.

In patients with neuropathic pain, topical forms of both capsaicin and lidocaine have been shown to be useful in the treatment of postherpetic neuralgia and diabetic peripheral neuropathic pain.


Comprehensive Review of Topical Analgesics for Chronic Pain.

There is evidence to support the use of topical NSAIDs, high concentration topical capsaicin, and topical lidocaine for various painful conditions.


Risk of systemic toxicity with topical lidocaine/prilocaine: a review.

All 12 clinical trials evaluating the safety of EMLA in either the pediatric or adult population generally followed dosing and administration guidelines set by the manufacturer and reported clinically insignificant plasma levels of methemoglobin, lidocaine, prilocaine, and their respective metabolites.


Efficacy and safety profile of a topical methyl salicylate and menthol patch in adult patients with mild to moderate muscle strain: a randomized, double-blind, parallel-group, placebo-controlled, multicenter study.

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

The primary efficacy analysis (SPID8 with movement) indicated that patients receiving the active patch experienced significantly greater pain relief (approximately 40%) than those patients receiving a placebo patch (mean [SD], 182.6 [131.2] vs 130.1 [144.1]; P = 0.005).


Menthol-Based Topical Analgesic Induces Similar Upper and Lower Body Pain Pressure Threshold Values: A Randomized Trial.

A menthol-based topical analgesic increased PPT (decreased pain sensitivity) overall (P = .05; 11.6% [2.4%]; d = 1.05) and PPT was higher (P < .0001; 31.5%-44.2%; d = 1.03-1.8) for lower versus upper body locations.


A randomized, double-blind comparison shows the addition of oxygenated glycerol triesters to topical mentholated cream for the treatment of acute musculoskeletal pain demonstrates incremental benefit over time.

Patients in both groups experienced statistically significant pain relief on Day 8 over baseline, with the MC plus OGT-treated group reporting statistically significantly greater pain relief than the MC group (P = 0.016).


Delayed-Onset Muscle Soreness and Topical Analgesic Alter Corticospinal Excitability of the Biceps Brachii.

Topical Menthol (Cooling Counterirritant)

These findings suggest that DOMS reduced corticospinal excitability and after the administration of menthol-based topical analgesic, there was a reduction in pain, which was accompanied by increased corticospinal inhibition.


The effect of either topical menthol or a placebo on functioning and knee pain among patients with knee OA.

The menthol intervention resulted in significant reductions in pain during the TUG, TCS, Up stairs, and Down stairs tasks. The placebo condition did not result in any significant changes in pain during the functional tasks.


A comparison of topical menthol to ice on pain, evoked tetanic and voluntary force during delayed onset muscle soreness.

Compared to ice, the topical menthol-based analgesic decreased perceived discomfort to a greater extent and permitted greater tetanic forces to be produced.


A cetylated fatty acid topical cream with menthol reduces pain and improves functional performance in individuals with arthritis.

One week of treatment with a topical cream consisting of cetylated fatty acids and menthol was similarly effective for reducing pain and improving functional performance in individuals with arthritis of the knee, elbow, and wrist.


The role and mechanism of action of menthol in topical analgesic products.

Menthol is a selective activator of transient receptor potential melastatin-8 (TRPM8) channels and is also a vasoactive compound. As a topical agent, it acts as a counter-irritant by imparting a cooling effect and by initially stimulating nociceptors and then desensitizing them.


The distinctive role of menthol in pain and analgesia: Mechanisms, practices, and advances.

Under pathological situation, menthol activates TRPM8 to attenuate mechanical allodynia and thermal hyperalgesia following nerve injury or chemical stimuli.


Menthol pain relief through cumulative inactivation of voltage-gated sodium channels.

We found that low concentrations of menthol cause analgesia in mice, relieving pain produced by a Na(+) channel-targeting toxin. We conclude that menthol is a state-selective blocker of Nav1.8, Nav1.9, and TTX-sensitive Na(+) channels, indicating a role for Na(+) channel blockade in the efficacy of menthol as topical analgesic compound.


Topical analgesics in the management of acute and chronic pain.

Currently, limited evidence is available to support the use of other topical analgesics in acute and chronic pain.


Topical Treatments and Their Molecular/Cellular Mechanisms in Patients with Peripheral Neuropathic Pain-Narrative Review.

For topical amitriptyline, menthol, and gabapentin, evidence comes from case reports and case series.


Topical therapies for knee osteoarthritis.

Many studies with a low level of evidence have reported some pain mitigation using the rest of aforementioned topical therapies.


Topical Analgesic Improved or Maintained Ballistic Hip Flexion Range of Motion with Treated and Untreated Legs.

Since menthol-based topical analgesics (TopAnalg) suppress pain, they may increase stretch thresholds improving ROM.


Improvement of Pain and Function After Use of a Topical Pain Relieving Patch: Results of the RELIEF Study.

Topical Methyl Salicylate + Menthol (Medicated Patch)

At day 14, TG pain severity score and pain interference score decreased (49% and 58.1%, respectively).


Study to determine the efficacy and onset of Bonipar, a topical analgesic for the management of acute and chronic musculoskeletal pain.

The success rates of achieving a 50 % pain reduction with Bonipar were found to be non-inferior to those treated with diclofenac.


Penetration capacity and local anti-inflammatory effect of a methyl salicylate gel with turpentine essence, camphor, and menthol for the symptomatic local treatment of muscular and joint pains.

The results showed that approximately 0.8% of the total applied methyl salicylate penetrated the skin with a time-dependent concentration increase.


A clinical and mechanistic study of topical borneol-induced analgesia.

Investigation of the actions of topical borneol and menthol revealed mechanistic differences between borneol- and menthol-induced analgesia and indicated that borneol exhibits advantages over menthol as a topical analgesic.


Topical analgesic added to paraffin enhances paraffin bath treatment of individuals with hand osteoarthritis.

The PTA group had greater improvement over the 12 treatment sessions for their pain at rest (t = 2.92, p < 0.05) and with movement (t = 4.73, p < 0.05) than the PO group.


Systematic review of efficacy of topical rubefacients containing salicylates for the treatment of acute and chronic pain.

Topical salicylate was significantly better than placebo (relative benefit 3.6, 95% confidence interval 2.4 to 5.6; number needed to treat 2.1, 1.7 to 2.8).


Diffusion modelling of percutaneous absorption kinetics. Predicting urinary excretion from in vitro skin permeation tests (IVPT) for an infinite dose.

Good linear IVIVRs for ethyl and glycol salicylates were obtained, but the IVIVR for methyl salicylate was poor, perhaps because of topical stimulation of local skin blood flow by methyl salicylate.


Herbal medicinal products or preparations for neuropathic pain.

There was insufficient evidence to determine whether nutmeg or St John's wort has any meaningful efficacy in neuropathic pain conditions.


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

Osteo Bi-Flex (Triple Strength + Joint Shield)

The 106 patients on placebo had a progressive joint-space narrowing, with a mean joint-space loss after 3 years of -0.31 mm (95% CI -0.48 to -0.13). There was no significant joint-space loss in the 106 patients on glucosamine sulphate: -0.06 mm (-0.22 to 0.09).


Glucosamine sulfate use and delay of progression of knee osteoarthritis: a 3-year, randomized, placebo-controlled, double-blind study.

Long-term treatment with glucosamine sulfate retarded the progression of knee osteoarthritis, possibly determining disease modification.


Effects of glucosamine, chondroitin, or placebo in patients with osteoarthritis of hip or knee: network meta-analysis.

Compared with placebo, glucosamine, chondroitin, and their combination do not reduce joint pain or have an impact on narrowing of joint space.


Effect of glucosamine and chondroitin sulfate in symptomatic knee osteoarthritis: a systematic review and meta-analysis of randomized placebo-controlled trials.

Oral supplementation with glucosamine or chondroitin sulfate reduces pain in knee OA. However, there is no additional effect using both therapeutic agents in combination for the management of symptomatic knee OA.

no-difference-cue: "no additional effect" | favorable-cue: "reduces pain"


The Efficacy and Safety of Disease-Modifying Osteoarthritis Drugs for Knee and Hip Osteoarthritis-a Systematic Review and Network Meta-Analysis.

Glucosamine and chondroitin yielded statistically significant but clinically questionable long-term benefit on structure and symptoms, though both had favorable safety profiles.


Glucosamine and chondroitin sulfate as therapeutic agents for knee and hip osteoarthritis.

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

On the basis of the results of recent randomised controlled trials and meta-analyses, we can conclude that glucosamine sulfate (but not glucosamine hydrochloride) and chondroitin sulfate have small-to-moderate symptomatic efficacy in OA, although this is still debated.


Effects of glucosamine and chondroitin sulfate supplementation in addition to resistance exercise training and manual therapy in patients with knee osteoarthritis: A randomized controlled trial.

Manual therapy and resistance exercise training are effective in the management of knee osteoarthritis, however, glucosamine and chondroitin sulfate supplementation for 4 weeks showed no additional benefits.

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


Comparison of Glucosamine-Chondroitin Sulfate with and without Methylsulfonylmethane in Grade I-II Knee Osteoarthritis: A Double Blind Randomized Controlled Trial.

combination of glucosamine-chondroitinsulfate-methylsulfonylmethane showed clinical benefit for patients with knee OAK ellgren-Lawrence grade I-II compared with GC and placebo.


Structure-modifying effects of chondroitin sulfate in knee osteoarthritis: an updated meta-analysis of randomized placebo-controlled trials of 2-year duration.

These results demonstrate that chondroitin sulfate is effective for reducing the rate of decline in minimum joint space width in patients with knee OA.


Symptom and structure modification in osteoarthritis with pharmaceutical-grade chondroitin sulfate: what's the evidence?

It increases type II collagen and proteoglycan synthesis in human articular chondrocytes and is able to reduce the production of some pro-inflammatory factors and proteases, to reduce the cellular death process, and improve the anabolic/catabolic balance of the extracellular cartilage matrix (ECM).


[Use of ARTRA MSM FORTE in patients with knee osteoarthritis: Results of a randomized open-label comparative study of the efficacy and tolerability of the drug].

Analysis of the results showed a significant decrease in pain on VAS in both groups. Reduced pain intensity was observed by the end of the first month of therapy and remained throughout the follow-up.


Effect of a glucosamine-based combination supplement containing chondroitin sulfate and antioxidant micronutrients in subjects with symptomatic knee osteoarthritis: A pilot study.

the tested glucosamine-based combination supplement is likely to have a beneficial effect on pain and other symptoms associated with knee OA.


Glucosamine and Chondroitin Use and Mortality Among Adults in the United States from 1999 to 2014.

Despite glucosamine and chondroitin use appearing to be inversely associated with mortality in the minimally adjusted models, no association was observed in multivariable models (glucosamine: HR = 1.02; 95% confidence interval [CI]: 0.86-1.21, chondroitin: HR = 1.04, 95% CI: 0.87-1.25).


OARSI guidelines for the non-surgical management of knee osteoarthritis.

Treatments of uncertain appropriateness for specific clinical sub-phenotypes included acupuncture, avocado soybean unsaponfiables, chondroitin, crutches, diacerein, glucosamine, intra-articular hyaluronic acid, opioids (oral and transdermal), rosehip, transcutaneous electrical nerve stimulation, and ultrasound.


Using the Rise and Fall of Oxidative Stress and Inflammation Post-Exercise to Evaluate the Effect of Methylsulfonylmethane Supplementation on Immune Response mRNA.

This study is the first to demonstrate significant effects with lower MSM doses (0.5-1.0 g/d) compared to previous work using higher doses (3 g/d).


Evaluating the Impacts of Methylsulfonylmethane on Allergic Rhinitis After a Standard Allergen Challenge: Randomized Double-Blind Exploratory Study.

All MSM treatment courses significantly reduced visual analog scale average nasal symptoms in a longitudinal comparison across all participants, with low-dose treatments decreasing symptoms by 53.72% (P=.001), and an acute 12-g dose decreasing symptoms by 22.49% (P=.03).


Methylsulfonylmethane and boswellic acids versus glucosamine sulfate in the treatment of knee arthritis: Randomized trial.

On the basis of these preliminary data, we could support the efficacy of the MSM in association with BA in the treatment of OA.


Nutraceutical Approach to Chronic Osteoarthritis: From Molecular Research to Clinical Evidence.

a great interest has been applied to nutraceutical supplements, which include a heterogeneous class of molecules with great potential to reduce inflammation, oxidative stress, pain, and joint stiffness and improve cartilage formation.


Dietary Thiols: A Potential Supporting Strategy against Oxidative Stress in Heart Failure and Muscular Damage during Sports Activity.

We will mainly focus on six natural antioxidants: glutathione, taurine, lipoic acid, sulforaphane, garlic and methylsulfonylmethane.


Delayed-Release Phosphatidylcholine Is Effective for Treatment of Ulcerative Colitis: A Meta-Analysis.

The meta-analysis of 3 RTCs with 160 included patients with ulcerative colitis verified that PC improved the rate of remission (OR = 9.68), as well as clinical (OR = 30.58) and endoscopic outcomes (OR = 36.73).


Phosphatidylcholine for steroid-refractory chronic ulcerative colitis: a randomized trial.

The primary end point was achieved in 15 of 30 (50%) phosphatidylcholine recipients and in 3 of 30 (10%) placebo recipients (difference, 40% [95% CI, 19% to 61%]; P = 0.002).


Retarded release phosphatidylcholine benefits patients with chronic active ulcerative colitis.

Induction of clinical remission (CAI < or = 3) as the primary outcome variable was attained by 16 (53%) patients in the phosphatidylcholine treated group compared with three (10%) in the placebo group (p<0.00001).


Delayed release phosphatidylcholine in chronic-active ulcerative colitis: a randomized, double-blinded, dose finding study.

We found a saturable dose response of rPC in the treatment of chronic-active ulcerative colitis with effective doses >or=1 g per day; doses of 3 and 4 g seem to be superior in achieving remission.


Mucosal protection by phosphatidylcholine.

In three clinical trials, when missing mucus PC in UC was supplemented by an oral, delayed release PC preparation, the inflammation improved and even resolved after a 3-month treatment course.


Activity of essential phospholipids (EPL) from soybean in liver diseases.

Clinical studies, primarily from European and Asian countries, have shown improvement in subjective symptoms; clinical, biochemical and imaging findings; and histology in liver indications such as fatty liver of different origin, drug hepatotoxicity, and adjuvant in chronic viral hepatitis and hepatic coma.


II. Veterans Affairs Cooperative Study of polyenylphosphatidylcholine in alcoholic liver disease.

PPC treatment for 2 years did not affect progression of liver fibrosis. A trend in favor of PPC was seen for transaminases and bilirubin (in subgroups).


New concepts of the pathogenesis of alcoholic liver disease lead to novel treatments.

PPC was beneficial in patients with alcoholic hepatitis, and it opposed fibrosis in heavy drinkers and decreased aminotransferases in patients with hepatitis C.


Polyene Phosphatidylcholine Ameliorates High Fat Diet-Induced Non-alcoholic Fatty Liver Disease Remodeling Metabolism and Inflammation.

PPC supplementation significantly mitigated liver steatosis and improved glucose tolerance and insulin sensitivity in HFD mice, which was accompanied by declined levels of hepatic triglyceride, serum triglyceride, low density lipoprotein, aspartate aminotransferase, and alanine aminotransferase.


Inhibiting SCAP/SREBP exacerbates liver injury and carcinogenesis in murine nonalcoholic steatohepatitis.

Supplementation with phosphatidylcholines significantly improved liver injury and ER stress induced by SCAP deletion.


Randomised trial of chronic supplementation with a nutraceutical mixture in subjects with non-alcoholic fatty liver disease.

The trial failed to demonstrate any efficacy on relevant physiopathological markers, but its protocol and results may be useful to design future studies with natural compounds.

no-difference-cue: "failed to demonstrate"


Choline supplements: An update.

Extensively used as food supplements, they have been shown to represent an effective strategy for boosting memory and enhancing cognitive function.


Phosphatidylcholine supplementation in pregnant women consuming moderate-choline diets does not enhance infant cognitive function: a randomized, double-blind, placebo-controlled trial.

Phosphatidylcholine supplementation of pregnant women eating diets containing moderate amounts of choline did not enhance their infants' brain function.


Pathways of acetylcholine synthesis, transport and release as targets for treatment of adult-onset cognitive dysfunction.

Controlled clinical studies denied clinical usefulness of choline and lecithin (phosphatidylcholine)


ABCA7 variants impact phosphatidylcholine and mitochondria in neurons.

Supplementation with CDP-choline increased phosphatidylcholine synthesis, reversed these abnormalities and normalized amyloid-β secretion and neuronal hyperexcitability-key Alzheimer's features that are exacerbated by ABCA7 dysfunction.


Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk.

Increased plasma levels of TMAO were associated with an increased risk of a major adverse cardiovascular event (hazard ratio for highest vs. lowest TMAO quartile, 2.54; 95% confidence interval, 1.96 to 3.28; P<0.001).


Trimethylamine N-oxide is associated with long-term mortality risk: the multi-ethnic study of atherosclerosis.

Higher TMAO levels associated with higher risk of all-cause mortality [hazard ratio (HR): 1.12, 95% confidence interval (CI): 1.08-1.17], CVD mortality (HR: 1.09, 95% CI: 1.00-1.09), and death due to kidney failure (HR: 1.44, 95% CI: 1.25-1.66) per inter-quintile range, but not deaths due to cancer or dementia.


Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease.

Three metabolites of the dietary lipid phosphatidylcholine--choline, trimethylamine N-oxide (TMAO) and betaine--were identified and then shown to predict risk for CVD in an independent large clinical cohort.


Validation of the Withings ScanWatch as a Wrist-Worn Reflective Pulse Oximeter: Prospective Interventional Clinical Study.

In a prospective validation against arterial blood-gas co-oximetry under controlled hypoxia, a wrist-worn reflective oximeter showed a bias of only 0.98% (95% CI 0.65-1.32).


Performance of Wearable Pulse Oximetry During Controlled Hypoxia Induction: Instrument Validation Study.

Wearable pulse oximetry maintained instrument validity during controlled hypoxia induction, supporting its use for trend monitoring.


Racial Bias in Pulse Oximetry Measurement.

Occult hypoxemia (true SaO2 below 88% despite an SpO2 of 92-96%) occurred nearly three times more often in Black than in White patients (11.7% vs 3.7% of measurements).


Routes of chloroform exposure and body burden from showering with chlorinated tap water.

Risk analysis : an official publication of the Society for Risk Analysis

After a normal shower, breath chloroform rose to 6-21 µg/m³, and the dermal dose absorbed during showering was approximately equal to the inhaled dose.


Ingestion, inhalation, and dermal exposures to chloroform and trichloroethene from tap water.

Human biomonitoring confirmed that ingestion, inhalation, and dermal contact with tap water all contribute meaningfully to chloroform body burden, so showering is not a trivial exposure route.


Chloronitramide anion is a decomposition product of inorganic chloramines.

A previously unknown chloramine by-product was detected in US drinking-water systems serving over 100 million people, highlighting how poorly characterized chloramine-era disinfection by-products remain.


Using TENS for pain control: the state of the evidence.

Mechanistic review: TENS acts through gate-control modulation and endogenous opioids, but effects are symptomatic and short-lived, and repeated use can induce opioid tolerance.


Management of chronic pain associated with temporomandibular disorders: a clinical practice guideline.

An international BMJ guideline suggests TENS among the non-drug options for chronic temporomandibular disorder pain - one of the few recent guidelines to endorse it for a specific condition.


Effect of High-Dose Omega-3 Fatty Acids vs Corn Oil on Major Adverse Cardiovascular Events in Patients at High Cardiovascular Risk: The STRENGTH Randomized Clinical Trial.

In 13,078 high-risk patients (STRENGTH), 4 g/day EPA+DHA carboxylic acids showed no cardiovascular benefit over corn oil (HR 0.99), with more atrial fibrillation in the omega-3 group.


Regular use of fish oil supplements and course of cardiovascular diseases: prospective cohort study.

In 415,737 UK Biobank participants, regular fish-oil use was associated with higher incident atrial fibrillation (HR 1.13) in people without cardiovascular disease, yet with slower progression to adverse events in those with existing disease.

unfavorable-cue: "associated with higher"


Nicotinamide for Skin Cancer Chemoprevention.

In a propensity-matched cohort of 33,822 veterans, oral nicotinamide use was associated with about 16% lower skin-cancer risk - observational support for, not proof of, the randomized chemoprevention signal.


Topical 8% glycolic acid and 8% L-lactic acid creams for the treatment of photodamaged skin. A double-blind vehicle-controlled clinical trial.

In a 22-week double-blind vehicle-controlled trial of 74 patients, an 8% glycolic acid cream modestly but significantly improved overall photodamage severity and sallowness versus vehicle (P<.05).


Glycolic acid treatment increases type I collagen mRNA and hyaluronic acid content of human skin.

Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.]

In a controlled human skin study with biopsy confirmation, topical glycolic acid increased type I collagen mRNA and epidermal/dermal hyaluronic acid, indicating dermal remodeling beyond surface exfoliation.


Humidification of indoor air for preventing or reducing dryness symptoms or upper respiratory infections in educational settings and at the workplace.

The Cochrane database of systematic reviews

Across 13 studies with over 4,500 participants, indoor-air humidification gave low-certainty benefit for dry-eye symptoms (OR 0.54) but little effect on dry nose or skin, and no included study reported respiratory-infection outcomes.


Indoor air humidity, air quality, and health - An overview.

International journal of hygiene and environmental health

Review synthesizing evidence that low indoor humidity drives dryness symptoms of eyes, skin and airways and raises infection susceptibility, supporting a roughly 40-60% RH target band.


Seasonality of Respiratory Viral Infections.

Review of animal and human data showing low humidity and temperature enhance respiratory-virus stability in aerosols and impair host mucosal immune defense, explaining winter seasonality.


Indoor air humidity revisited: Impact on acute symptoms, work productivity, and risk of influenza and COVID-19 infection.

Updated analysis linking mid-range indoor humidity to fewer acute dryness symptoms, better work productivity, and lower modeled influenza and COVID-19 risk.


Use of sunscreen and risk of melanoma and non-melanoma skin cancer: a systematic review and meta-analysis.

Systematic review and meta-analysis supporting a protective association between sunscreen use and melanoma and non-melanoma skin cancer, while noting confounding in the observational data.


Multicenter evaluation of a topical hyaluronic acid serum.

A multicenter clinical evaluation found a topical hyaluronic acid serum measurably improved skin hydration and visible signs of aging.


Oral Hyaluronan Relieves Wrinkles and Improves Dry Skin: A 12-Week Double-Blinded, Placebo-Controlled Study.

In a double-blind placebo-controlled trial of 40 adults, 120 mg/day oral hyaluronan for 12 weeks significantly improved wrinkle scores, stratum-corneum water content, TEWL and elasticity (industry-funded).


Oral hyaluronan relieves wrinkles: a double-blinded, placebo-controlled study over a 12-week period.

Clinical, cosmetic and investigational dermatology

A second independent double-blind placebo-controlled trial confirmed that 12 weeks of oral hyaluronan significantly reduces wrinkles versus placebo.


Preventive effect of foam rolling on muscle soreness after exercise: A systematic review and meta-analysis.

Journal of bodywork and movement therapies

Meta-analysis of 16 RCTs (n=515): foam rolling moderately reduces post-exercise muscle soreness at 24 h (SMD -0.53) and 48 h (SMD -0.77), with little immediate effect.


Effect of whole-body vibration training on bone mineral density in older adults: a systematic review and meta-analysis.

Meta-analysis of 7 RCTs (n=202): BMD benefit was significant only at the total femur (g=0.28) and null at the femoral neck and lumbar spine; certainty rated low.


Effects of whole-body vibration training with different frequencies on the balance ability of the older adults: a network meta-analysis.

Network meta-analysis: whole-body vibration improves balance in older adults, with frequency-dependent effects.


Efficacy of a Naturally Calcium and Magnesium-Rich Mineral Water on Musculoskeletal Fragility: A Randomized, Double-Blind Controlled Trial.

Double-blind RCT (n=98, adults over 50): daily calcium/magnesium-rich mineral water cut falls by 82% at 6 months and improved appendicular muscle mass over 12 months — tested bottled mineral water, not drops.


Effectiveness of wearable activity trackers to increase physical activity and improve health: a systematic review of systematic reviews and meta-analyses.

Biometric Wearables (Sleep, HRV & Recovery)

Umbrella review of 39 meta-analyses (163,992 participants): trackers add roughly 1,800 steps/day and 40 min/day of walking with about 1 kg weight loss — enough for the authors to recommend them.


A Validation of Six Wearable Devices for Estimating Sleep, Heart Rate and Heart Rate Variability in Healthy Adults.

Six-device lab validation against polysomnography/ECG: Oura and WHOOP were the strongest for sleep and HR/HRV, but multi-stage sleep classification reached only about 50-64% agreement across devices.


Apple watch accuracy in monitoring health metrics: a systematic review and meta-analysis.

56-study meta-analysis: Apple Watch heart rate is accurate (mean bias -0.12 bpm) and step counts acceptable, but energy-expenditure estimates failed validity thresholds in every subgroup.


A validation study of the WHOOP strap against polysomnography to assess sleep.

WHOOP agreed with polysomnography on 89% of epochs for sleep vs. wake (95% sleep sensitivity) and overestimated total sleep time by only about 8 minutes.


Accuracy of the wearable activity tracker Garmin Forerunner 235 for the assessment of heart rate during rest and activity.

Garmin wrist heart rate was accurate at rest (r=0.997) and during running (r 0.85-0.91) but degraded during low-intensity cycling (r about 0.27-0.46).


Usability and Accuracy of a Smartwatch for the Assessment of Physical Activity in the Elderly Population: Observational Study.

Garmin vívoactive step counts matched hand-tallied counts almost perfectly (ICC 0.98) in adults aged 70-90 during real-life walks.


The Sleep of the Ring: Comparison of the ŌURA Sleep Tracker Against Polysomnography.

Early Oura validation (n=41): 96% sensitivity for detecting sleep but only 48% specificity for wake, with REM overestimated by about 17 minutes — staging has improved with newer algorithms.


Wearable activity trackers for promoting physical activity: A systematic meta-analytic review.

International journal of medical informatics

44-trial review: trackers increase daily steps and weekly moderate-to-vigorous activity but do not reduce sedentary time; effects are larger with professional support.


Heart Rate Variability-Guided Training for Enhancing Cardiac-Vagal Modulation, Aerobic Fitness, and Endurance Performance: A Methodological Systematic Review with Meta-Analysis.

International journal of environmental research and public health

Meta-analysis: adjusting training by morning HRV improved vagal HRV indices more than fixed plans (SMD 0.50), but VO2max and performance advantages were small and not significant.


Interventions Using Wearable Activity Trackers to Improve Patient Physical Activity and Other Outcomes in Adults Who Are Hospitalized: A Systematic Review and Meta-analysis.

Across 15 studies (n=1,911), wearable-tracker interventions significantly increased objectively measured physical activity in hospitalized and rehabilitation patients.


Association of Cardiorespiratory Fitness With Long-term Mortality Among Adults Undergoing Exercise Treadmill Testing.

In 122,007 adults (1.1 million person-years), mortality fell monotonically with cardiorespiratory fitness — elite vs. low fitness HR 0.20, with no upper limit of benefit observed.


Effects of creatine supplementation on memory in healthy individuals: a systematic review and meta-analysis of randomized controlled trials.

Meta-analysis of 8 RCTs: creatine improves memory modestly overall (SMD 0.29), with the largest effect in adults aged 66-76 (SMD 0.88).


Creatine monohydrate for lean mass, strength, and bone density in postmenopausal women: a systematic review and meta-analysis.

Journal of the International Society of Sports Nutrition

Meta-analysis of 7 RCTs (n=608): in postmenopausal women, creatine at 5 g/day or more plus resistance training raised leg-press strength (+7.5 kg 1RM), with no bone-density effect and adverse events similar to placebo.

favorable-cue: "raised leg-press strength"


International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine.

Position stand: creatine monohydrate is the most effective ergogenic nutritional supplement for high-intensity exercise and lean mass, with an extensive safety record.


The Effects of Massage Guns on Performance and Recovery: A Systematic Review.

Journal of functional morphology and kinesiology

A systematic review of 11 trials (most with moderate risk of bias) found massage guns improve short-term flexibility and recovery but do not improve — and may transiently impair — strength, power, and agility.

no-difference-cue: "do not improve" | favorable-cue: "improve"


Under the Gun: Percussive Massage Therapy and Physical and Perceptual Recovery in Active Adults.

A 5-minute massage-gun application after strenuous lower-body exercise improved perceptual and physical recovery outcomes in active adults.


Effects of percussive massage therapy on fascia echo intensity and fascia thickness in firefighters with chronic non-specific low back pain: a randomized controlled trial.

BMC complementary medicine and therapies

In firefighters with chronic low back pain, percussive massage produced ultrasound-documented reductions in thoracolumbar fascia thickness and echo intensity, a stiffness surrogate.


Investigating the effects of percussion massage therapy on pain, functionality, muscle diameter, and proprioception in ındividuals with ACL reconstruction: a randomized controlled trial.

Adding percussion massage to a structured exercise program after ACL reconstruction improved range of motion, pain, function, balance, and quality of life versus exercise alone in a small randomized trial.


The effects of astaxanthin supplementation on obesity, blood pressure, CRP, glycemic biomarkers, and lipid profile: A meta-analysis of randomized controlled trials.

Across 14 randomized trials, astaxanthin slightly raised HDL-C and lowered CRP only at high doses or longer durations, with no significant effects on weight, blood pressure, glycemic markers, or other lipids.

no-difference-cue: "no significant effects" | favorable-cue: "lowered crp"


Effects of Astaxanthin Supplementation on Fatigue, Motor Function and Cognition: A Meta-Analysis of Randomized Controlled Trials.

A meta-analysis of randomized trials reported that astaxanthin supplementation improved fatigue and selected cognitive and motor outcomes.


Zinc lozenges and the common cold: a meta-analysis comparing zinc acetate and zinc gluconate, and the role of zinc dosage.

Across 7 randomized trials (n=575), zinc lozenges providing more than 75 mg/day elemental zinc shortened common-cold duration by about 33%, with no added benefit above roughly 100 mg/day.


A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8.

Archives of ophthalmology (Chicago, Ill. : 1960)

In 3,640 at-risk older adults followed about 6 years, high-dose zinc (80 mg) combined with antioxidant vitamins reduced progression to advanced age-related macular degeneration (OR 0.72).


Lutein + zeaxanthin and omega-3 fatty acids for age-related macular degeneration: the Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial.

In 4,203 participants, adding lutein/zeaxanthin or omega-3s to the AREDS formulation gave no further protection against advanced AMD, and lowering the zinc dose made no apparent difference.

no-difference-cue: "no apparent difference"


Selenium and coenzyme Q(10) improve the systemic redox status while reducing cardiovascular mortality in elderly population-based individuals.

A KiSel-10 biomarker analysis found combined selenium and CoQ10 improved systemic redox status in parallel with the trial's reduced cardiovascular mortality.


Increased SIRT1 Concentration Following Four Years of Selenium and Q(10) Intervention Associated with Reduced Cardiovascular Mortality at 10-Year Follow-Up-Sub-Study of a Previous Prospective Double-Blind Placebo-Controlled Randomized Clinical Trial.

Four years of selenium plus CoQ10 raised concentrations of SIRT1, a longevity-associated deacetylase, in association with reduced cardiovascular mortality at 10-year follow-up.

favorable-cue: "reduced cardiovascular mortality"


Selenium and Coenzyme Q(10) Supplementation and Sex Differences in Cardiovascular Mortality Results from a Prospective Randomized Double-Blind Placebo-Controlled Trial in Elderly People Low in Selenium.

A KiSel-10 sex-stratified analysis found the cardiovascular survival benefit of selenium plus CoQ10 was greater — and appeared later — in women than in men.


Micronutrient Supplementation to Reduce Cardiovascular Risk.

Journal of the American College of Cardiology

A JACC systematic review placed selenium plus CoQ10 among the few micronutrient interventions with randomized cardiovascular-outcome data.


The effect of vitamin MK-7 on bone mineral density and microarchitecture in postmenopausal women with osteopenia, a 3-year randomized, placebo-controlled clinical trial.

Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA

Despite a 65% fall in undercarboxylated osteocalcin, 375 µg/day MK-7 for 3 years did not improve bone mineral density, turnover markers, or microarchitecture in postmenopausal women with osteopenia.


Effect of Menaquinone-7 (MK-7) Supplementation on Anthropometric Measurements, Glycemic Indices, and Lipid Profiles: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

A 2025 meta-analysis of randomized trials found MK-7 supplementation modestly improved some glycemic indices and lipid measures.


The influence of white noise on sleep in subjects exposed to ICU noise.

In a small polysomnography experiment, white noise attenuated the arousals caused by recorded ICU noise, showing that acoustic masking works in loud environments.


Noise as a sleep aid: A systematic review.

Across 38 studies, the GRADE quality of evidence that continuous noise improves sleep was rated very low — contradicting its widespread use — with possible negative effects on sleep and hearing.


Auditory and non-auditory effects of noise on health.

An authoritative review concluding that environmental noise disturbs sleep and contributes to the burden of cardiovascular disease.


Efficacy and safety of milk thistle preventive treatment of anti-tuberculosis drug-induced liver injury: A protocol for systematic review and meta-analysis.

Prophylactic milk thistle lowered the incidence of anti-tuberculosis drug-induced liver injury in a randomized trial.


Tea Consumption and All-Cause and Cause-Specific Mortality in the UK Biobank : A Prospective Cohort Study.

Among ~498,000 UK Biobank participants followed a median 11.2 years, drinking 2–3 cups of tea daily was associated with 13% lower all-cause mortality (HR 0.87, 95% CI 0.84–0.91), an observational association that cannot prove cause.

favorable-cue: "lower all-cause mortality"


Coffee and Green Tea Consumption and Cardiovascular Disease Mortality Among People With and Without Hypertension.

Journal of the American Heart Association

Green tea consumption was associated with lower cardiovascular disease mortality in cohort analyses that included people with hypertension.


Hepatotoxicity with High-Dose Green Tea Extract: Effect of Catechol-O-Methyltransferase and Uridine 5'-Diphospho-glucuronosyltransferase 1A4 Genotypes.

A human pharmacogenetic study indicating that COMT and UGT genetic variability helps explain individual susceptibility to green tea extract liver injury.


Efficacy and safety of antioxidant treatment with α-lipoic acid over 4 years in diabetic polyneuropathy: the NATHAN 1 trial.

In the 4-year NATHAN 1 trial, ALA improved neuropathy symptoms but did not significantly improve the primary neuropathy-impairment composite, leaving disease modification unproven.

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


The effect of alpha-lipoic acid on inflammatory mediators: a systematic review and meta-analysis on randomized clinical trials.

A meta-analysis of 19 RCTs found ALA significantly lowered CRP, IL-6, and TNF-α, though with very high heterogeneity across studies.

favorable-cue: "significantly lowered crp"


The effects of light therapy on sleep problems: A systematic review and meta-analysis.

In a meta-analysis of 53 studies (n=1,154), light therapy improved sleep problems overall (g~0.39), with effects for insomnia (g~0.47), circadian-rhythm sleep disorders (g~0.41), and dementia-related sleep disturbance (g~0.30).


Light therapy in insomnia disorder: A systematic review and meta-analysis.

Systematic review and meta-analysis supporting light therapy as an effective intervention for insomnia disorder.


Efficacy and safety of coenzyme Q10 in heart failure: a meta-analysis of randomized controlled trials.

In a meta-analysis of 33 randomized heart-failure trials, coenzyme Q10 lowered all-cause mortality (RR 0.64) and heart-failure hospitalization (RR 0.50) and improved ejection fraction and 6-minute walk distance, with moderate GRADE certainty for key outcomes.


Coenzyme Q10 for heart failure.

Cochrane review rated the evidence for coenzyme Q10 in heart failure as low to very low certainty and called for larger trials, tempering more optimistic meta-analyses.


High-dose ubiquinol supplementation in multiple-system atrophy: a multicentre, randomised, double-blinded, placebo-controlled phase 2 trial.

In a multicentre double-blind phase 2 RCT (n=139), high-dose ubiquinol (1,500 mg/day) slowed functional decline in multiple system atrophy (UMSARS part 2 difference -1.7 vs placebo) and was well tolerated.


Ubiquinol Ameliorates Endothelial Dysfunction in Subjects with Mild-to-Moderate Dyslipidemia: A Randomized Clinical Trial.

Randomized trial in which ubiquinol improved endothelial function in people with mild-to-moderate dyslipidemia.


Reference ranges of handgrip strength from 125,462 healthy adults in 21 countries: a prospective urban rural epidemiologic (PURE) study.

Journal of cachexia, sarcopenia and muscle

Grip-Strength Dynamometer;Hand Grip Dynamometer Pro

PURE normative study providing age- and sex-specific grip-strength reference ranges from 125,462 healthy adults in 21 countries.


Validity and reliability of Squegg device in measuring isometric handgrip strength.

European review for medical and pharmacological sciences

Validation study finding a consumer Bluetooth dynamometer (Squegg) measures isometric grip strength with acceptable validity and reliability against a clinical reference device.


Handgrip strength measurement protocols for all-cause and cause-specific mortality outcomes in more than 3 million participants: A systematic review and meta-regression analysis.

Clinical nutrition (Edinburgh, Scotland)

Meta-regression of measurement protocols across more than 3 million participants found that how grip strength is measured materially affects its prognostic estimates, supporting standardized testing.


Melasma Treatment: An Evidence-Based Review.

American journal of clinical dermatology

An evidence-based dermatology review counts topical tranexamic acid among the supported options for melasma, while noting most trials are short and heterogeneous.


Nonvalidated Home Blood Pressure Devices Dominate the Online Marketplace in Australia: Major Implications for Cardiovascular Risk Management.

In an audit of 972 devices from 59 online sellers, only about 5.5% of devices on international e-commerce sites had passed accuracy validation, so most home BP monitors sold online are unvalidated.


Effects of whole-body electromyostimulation on health indicators of older people: Systematic review and meta-analysis of randomized trials.

Across 13 randomized trials in adults over 60, whole-body EMS produced a large improvement in sarcopenia composite score versus controls (effect size 1.44).


Whole-body electromyostimulation and protein supplementation favorably affect sarcopenic obesity in community-dwelling older men at risk: the randomized controlled FranSO study.

In sarcopenic-obese older men, 16 weeks of whole-body EMS plus protein raised handgrip strength (+1.9 kg versus control) and reduced body fat (-2.1%) without adverse effects.


The effectiveness of neuromuscular electrical stimulation on pain, function, and quadriceps muscle strength in adults with patellofemoral pain: A systematic review and meta-analysis.

Adding NMES to exercise improved knee function (SMD 3.74) and quadriceps strength (SMD 0.53) in patellofemoral pain, but certainty of evidence was rated very low and it did not beat exercise alone for pain relief.


A Systematic Risk Assessment and Meta-Analysis on the Use of Oral β-Alanine Supplementation.

A safety meta-analysis found oral beta-alanine had no adverse effects on clinical blood, liver or kidney markers; transient paresthesia (tingling) was the only consistent side effect.


The absorption of orally supplied beta-alanine and its effect on muscle carnosine synthesis in human vastus lateralis.

Human muscle-biopsy work showed orally supplied beta-alanine is absorbed and taken up by skeletal muscle, where it increases carnosine synthesis, the basis of chronic dosing protocols.


β-Alanine supplementation improves fractional anisotropy scores in the hippocampus and amygdala in 60-80-year-old men and women.

In a 10-week randomized trial in 60-80-year-olds, beta-alanine improved hippocampal and amygdala fractional anisotropy on DTI, an early hint of central effects whose cognitive meaning is unproven.


Effect of carnosine or beta-alanine supplementation therapy for prediabetes or type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials.

A 2025 meta-analysis of randomized trials evaluated carnosine or beta-alanine supplementation for glycemic control in prediabetes and type 2 diabetes, an emerging and still-preliminary research direction.