Dietary Luteolin Reduces Proinflammatory Microglia in the Brain of Senescent Mice

Dietary luteolin reduced age-related proinflammatory microglia activity in the brains of senescent mice.

Does dietary luteolin reduce microglia activity in the brain of senescent mice?

Hypothesis: Feeding aged mice a diet with luteolin would reduce microglia activity.

Adult (3-6 months) and aged (22-24 months) mice were fed either a control diet (AIN-93M) or a diet supplemented with luteolin (6 g/kg) for 4 weeks. They were then injected with either saline or lipopolysaccharide (LPS). Microglia were isolated and stained for MHC class II, IL-1β, and IL-6 for flow cytometry.

In saline-treated mice on a control diet, aging increased the proportion of microglia staining for MHC class II (from <3% in adults to 23% in aged), IL-1β (from <2% in adults to 25% in aged), and IL-6 (from <2% in adults to 25% in aged). In saline-treated aged mice fed luteolin, these proportions were reduced by nearly half to 12% for MHC class II, 13% for IL-1β, and 12% for IL-6. Luteolin also significantly reduced IL-1β and IL-6 staining in LPS-treated adult mice, but not in aged mice.

A diet supplemented with luteolin inhibited brain microglia activity during aging and also inhibited activation by LPS in adult mice. Luteolin may inhibit neuroinflammation and improve cognition in healthy aged individuals by constraining brain microglia.

The study did not investigate the effects of luteolin on LPS-treated aged mice for IL-1β and IL-6, as the reduction was not significant in this group.


Neuroprotective effects of flavone luteolin in neuroinflammation and neurotrauma

Luteolin, a natural compound, shows promise in protecting the brain by reducing inflammation and oxidative stress in various neurological conditions.

What are the neuroprotective effects of the flavone luteolin in neuroinflammation and neurotrauma?

Hypothesis: The authors hypothesize that luteolin, a natural polyphenol, exhibits neuroprotective effects by suppressing neuroinflammatory responses and related mechanisms.

This is a short review article. Data was collected from publications in PubMed using keywords such as 'luteolin and mast cells', 'neuroinflammation', 'neurodegenerative diseases', and 'TBI'.

Luteolin suppresses systemic and neuroinflammatory responses, including in COVID-19. It exhibits neuroprotective effects by suppressing immune cell activation (e.g., mast cells) and the release of inflammatory mediators. Luteolin also suppresses neuroinflammatory responses, activation of microglia and astrocytes, oxidative stress, and the severity of neuroinflammatory diseases like Alzheimer's, Parkinson's, multiple sclerosis, and TBI pathogenesis.

Luteolin can improve cognitive decline and enhance neuroprotection in neurodegenerative diseases, TBI, and stroke.

This is a review article, summarizing existing research rather than presenting new experimental data. The specific limitations of the reviewed studies are not detailed.


Dietary flavanols improve cerebral cortical oxygenation and cognition in healthy adults

Dietary flavanols can enhance brain oxygenation and improve cognitive function in healthy young adults, especially during demanding tasks.

Do dietary flavanols improve cerebral cortical oxygenation and cognition in healthy adults?

Hypothesis: The study hypothesized that flavanol intake would lead to faster and greater brain oxygenation responses and improved cognitive performance, with similar vascular mechanisms underlying both peripheral and cerebral effects.

This was a randomized, double-blind, within-subject acute study involving healthy young adults. The study measured brain oxygenation responses to hypercapnia and cognitive performance under varying demands after flavanol intake.

Flavanol intake resulted in faster and greater brain oxygenation responses to hypercapnia. It also led to higher cognitive performance, but only when cognitive demand was high. Individual analyses showed that participants who benefited from flavanols during hypercapnia also benefited in the cognitive challenge.

Dietary flavanols improve cerebral cortical oxygenation and cognition in healthy young adults, particularly under high cognitive demand. The findings support the hypothesis that similar vascular mechanisms are involved in both the peripheral and cerebral effects of flavanols.

The abstract does not explicitly state limitations, but it suggests the importance of further studies combining physiological and graded cognitive challenges.


Cocoa Flavanol Supplementation and Exercise: A Systematic Review

Cocoa flavanols may help with exercise-induced oxidative stress and metabolism, but don't seem to boost athletic performance directly.

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

What are the effects of cocoa flavanol (CF) intake on exercise performance, recovery, and exercise-induced changes in vascular function, cognitive function, oxidative stress, inflammation, and metabolic parameters?

Hypothesis: It has been suggested that cocoa flavanol intake may improve exercise performance and recovery due to its antioxidant, anti-inflammatory, and vascular function-improving capacities.

A systematic review was conducted by searching two electronic databases (Pubmed and Web of Science) for human studies combining CF intake and exercise up to March 28, 2017. Studies were included if the exact amount of CFs was specified. The methodological quality and bias of the 13 included studies were assessed using the Dutch Cochrane center's checklist for randomized controlled trials.

Acute, sub-chronic (2 weeks), and chronic (3 months) CF intake reduced exercise-induced oxidative stress. Acute CF intake reduced and tempered exercise-induced blood pressure increases in obese participants. Acute and sub-chronic CF intake altered fat and carbohydrate metabolism during exercise. Acute and sub-chronic CF intake did not show ergogenic effects in athletes, but chronic CF intake improved mitochondrial efficiency in untrained participants. Combining sub-chronic CF intake and exercise training improved cardiovascular risk factors and vascular function.

Cocoa flavanol intake may improve vascular function, reduce exercise-induced oxidative stress, and alter fat and carbohydrate utilization during exercise, but it does not appear to affect exercise performance. Evidence regarding CF's effects on exercise-induced inflammation, platelet activation, and synergistic effects with exercise training on oxidative stress, inflammation, and fat/glucose metabolism is limited.

The review found scarce evidence on the effect of CF on exercise-induced inflammation and platelet activation. There was also a lack of evidence on the synergistic effects of CF and exercise training on oxidative stress, inflammation, and fat and glucose metabolism.


Pycnogenol, French maritime pine bark extract, improves endothelial function of hypertensive patients

Pycnogenol supplementation may help reduce the required dose of blood pressure medication and improve endothelial function in mildly hypertensive patients.

Does Pycnogenol, a French maritime pine bark extract, improve endothelial function and reduce the need for antihypertensive medication in patients with hypertension?

Hypothesis: The study hypothesized that Pycnogenol supplementation would improve endothelial function and allow for a reduction in the dose of calcium antagonist medication in hypertensive patients.

A placebo-controlled, double-blind, parallel group study was conducted with 58 patients diagnosed with hypertension. Patients received either 100 mg of Pycnogenol or a placebo daily for 12 weeks. Endothelial function markers (endothelin-1, 6-keto prostaglandin F1a, nitric oxide, angiotensin II) and the required dose of nifedipine were measured.

Pycnogenol supplementation significantly reduced the dose of the calcium antagonist nifedipine. Endothelin-1 concentrations significantly decreased in the Pycnogenol group compared to placebo, while 6-keto prostaglandin F1a concentrations were significantly higher. Nitric oxide levels increased in both groups but not significantly, and angiotensin II concentrations were lowered more in the placebo group. Heart rate, electrolytes, and blood urea nitrogen remained unchanged in both groups. Mild and transient side effects were observed in both groups, with no significant difference in their rates.

Supplementation with Pycnogenol may be beneficial for mildly hypertensive patients, as it helped reduce the dose of nifedipine and improved certain markers of endothelial function.

The abstract does not explicitly state limitations beyond the observed side effects being mild and transient, and the non-significant changes in nitric oxide and angiotensin II.


Pilot Study of Tart Cherry Juice for the Treatment of Insomnia and Investigation of Mechanisms

Tart cherry juice may help older adults with insomnia sleep longer and more efficiently, possibly by affecting tryptophan metabolism and inflammation.

Can tart cherry juice improve insomnia confirmed by polysomnography in older adults, and is tryptophan availability a potential mechanism?

Hypothesis: Montmorency tart cherry juice will improve insomnia as measured by polysomnography, and this improvement may be linked to increased tryptophan availability through the inhibition of indoleamine 2,3-dioxygenase (IDO).

A placebo-controlled, balanced crossover study was conducted with subjects over 50 years old experiencing insomnia. Participants were randomized to receive either placebo or tart cherry juice (240 mL twice daily) for 2 weeks, separated by a 2-week washout period. Sleep was assessed using polysomnography and 5 validated questionnaires. Serum levels of indoleamine 2,3-dioxygenase (IDO), the kynurenine-to-tryptophan ratio, and prostaglandin E2 were measured. In vitro experiments stimulated Caco-2 cells with interferon-gamma to measure the ability of cherry juice procyanidin to inhibit IDO. The content of procyanidin B-2 and other major anthocyanins in the cherry juice was also determined.

Out of 11 randomized subjects, 8 completed the study after 3 were excluded due to sleep apnea. The completers showed an increase in sleep time by 84 minutes on polysomnography (P = 0.0182) and an increase in sleep efficiency on the Pittsburgh Sleep Quality Index (P = 0.03) when consuming cherry juice. Other questionnaires did not show significant differences. Serum kynurenine-to-tryptophan ratio and prostaglandin E2 levels both decreased (both P < 0.05). In vitro, cherry juice procyanidin B-2 dose-dependently inhibited IDO.

Tart cherry juice increased sleep time and sleep efficiency in older adults with insomnia. The procyanidin B-2 in cherry juice inhibited IDO, which may increase tryptophan availability and reduce inflammation, potentially contributing to the observed improvements in insomnia.

The study had a small sample size of 8 completers, which may limit the generalizability of the findings. Three subjects were excluded due to sleep apnea, indicating that the results may not apply to individuals with this condition.


affron a novel saffron extract improves mood in healthy adults over 4 weeks

A daily dose of 28mg of affron, a saffron extract, improved mood and reduced stress and anxiety in healthy adults with low mood.

Can a saffron extract (affron) improve mood, stress, anxiety, and sleep quality in healthy adults with self-reported low mood?

Hypothesis: Saffron extract (affron) will improve mood, stress, anxiety, and sleep quality in healthy adults.

This was a 4-week randomized, double-blind, placebo-controlled trial with 128 healthy adults who self-reported low mood. Participants were assigned to receive either 28mg/day of affron, 22mg/day of affron, or a placebo. Mood was assessed using POMS and PANAS questionnaires, DASS-21 scale, and sleep quality was monitored using the PSQI.

The 28mg/day dose of affron significantly decreased negative mood and symptoms related to stress and anxiety, showing a significant difference compared to placebo on the POMS Total Mood Disturbance scale. The 22mg/day dose did not show a treatment effect.

A 28mg/day dose of affron can increase mood and reduce anxiety and stress in healthy adults with self-reported low mood, without reported side effects.

The main limitations of this study were the self-reporting nature of both the screening process for participants and the outcome measures.


Effect of Saffron Versus SSRIs in Treatment of Depression and Anxiety: A Meta-analysis of Randomized Controlled Trials

Saffron appears to be as effective as SSRIs for depression and anxiety, with fewer side effects.

What is the comparative effectiveness of saffron versus selective serotonin reuptake inhibitors (SSRIs) in treating depression and anxiety?

Hypothesis: Saffron, a natural remedy, may have comparable antidepressant and anxiolytic properties to SSRIs.

A systematic review and meta-analysis was conducted by searching PubMed, Embase, Scopus, Web of Science, and the Cochrane database up to April 31, 2023. Randomized controlled trials (RCTs) comparing saffron with SSRIs in adults with depression or anxiety were included. Random-effects meta-analysis calculated standardized mean differences (SMDs) for continuous outcomes and risk ratios (RRs) for binary outcomes.

Meta-analysis of 8 studies on depression showed a nonsignificant difference between saffron and SSRIs in reducing depressive symptoms (SMD = 0.10). Four studies on anxiety also showed a nonsignificant difference between saffron and SSRIs in reducing anxiety symptoms (SMD = 0.04). Participants receiving saffron experienced fewer adverse events compared to the SSRI group (risk difference: -0.06).

Saffron may be a potential alternative to SSRIs for reducing depressive and anxiety symptoms, with the added benefit of fewer adverse events.

Further research with larger sample sizes and diverse populations is needed to validate these findings and investigate factors influencing treatment response.


Lutein and Zeaxanthin Supplementation Improves Dynamic Visual and Cognitive Performance

Lutein and zeaxanthin supplementation improved visual and cognitive function and reduced eye strain in children aged 5-12.

Can supplementation with lutein and zeaxanthin improve visual and cognitive performance in preadolescent children?

Hypothesis: Supplementation with lutein and zeaxanthin will improve visual and cognitive outcomes in preadolescent children, similar to findings in adults.

Sixty children (5-12 years old) were randomized in a 2:1 ratio to receive either gummies with 10 mg lutein and 2 mg zeaxanthin (LZ) or placebo for 180 days in a double-blind, placebo-controlled trial. Primary endpoint was macular pigment optical density (MPOD), with secondary endpoints including serum L and Z, BDNF, critical flicker fusion (CFF), eye strain/fatigue (VAS), sleep habits (CSHQ-A), and Creyos Health cognitive domains. Safety was monitored via physical exams, vital signs, lab tests, and adverse event tracking.

The LZ group showed significant increases in MPOD starting at day 42 and at all subsequent visits compared to placebo. Significant increases in serum lutein, reduced eye strain and fatigue, and improved cognitive performance (focus, episodic memory and learning, visuospatial working memory) were observed at days 90 and 180 in the LZ group. By day 180, the LZ group also showed significant increases in processing speed (CFF), attention, visuospatial processing, and serum Z and BDNF levels compared to placebo. No safety concerns were reported.

Supplementation with lutein and zeaxanthin in preadolescent children increased MPOD, serum L, Z, and BDNF levels, which were associated with improved visual and cognitive performance and reduced eye strain and fatigue. The supplement was safe and well tolerated.

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


Effects of a Lutein and Zeaxanthin Intervention on Cognitive Function: A Randomized, Double-Masked, Placebo-Controlled Trial

Targeted Organ-Support Nutrients;Lutein and Zeaxanthin

Lutein and zeaxanthin supplements may improve memory, reasoning, and attention in young adults.

Can supplementation with lutein (L) and zeaxanthin (Z) improve cognitive function in young, healthy adults?

Hypothesis: The study hypothesized that L + Z supplementation would improve cognitive function in young adults, based on previous findings in older adults.

Fifty-one young, healthy adults (age 18-30) were randomized into an active supplement group (n=37) or a placebo group (n=14). Macular pigment optical density (MPOD) and cognitive function, measured using the CNS Vital Signs platform, were assessed every four months over a one-year supplementation period.

Supplementation with L + Z significantly increased MPOD over the year compared to placebo. This daily supplementation and the increase in MPOD led to significant improvements in spatial memory, reasoning ability, and complex attention, beyond what could be attributed to practice effects.

Lutein and zeaxanthin supplementation can increase central nervous system xanthophyll levels and improve cognitive function in young, healthy adults.


Ubiquinol in patients with severe sepsis or septic shock: a randomized, double-blind, placebo-controlled pilot trial

Oral ubiquinol can increase CoQ10 levels in septic patients, but this pilot study did not show improvements in mitochondrial function or clinical outcomes.

no-difference-cue: "did not demonstrate"

Can exogenous ubiquinol increase plasma CoQ10 levels and improve mitochondrial function in patients with severe sepsis or septic shock?

Hypothesis: The provision of exogenous ubiquinol will increase plasma CoQ10 levels and improve mitochondrial function in patients with severe sepsis or septic shock, given previous findings of decreased CoQ10 in septic shock.

This was a randomized, double-blind, placebo-controlled pilot trial conducted at a single hospital. 38 adult patients (19 in each group) with severe sepsis or septic shock received either 200 mg enteral ubiquinol or placebo twice daily for up to seven days. Blood samples were collected at baseline, 12, 24, 48, and 72 hours to measure CoQ10 parameters (total, relative to cholesterol, oxidized, and reduced CoQ10) as the primary outcome, and secondary outcomes included vascular endothelial, inflammatory, and mitochondrial injury biomarkers, as well as clinical outcomes. Repeated measures models were used for group comparisons.

The ubiquinol group showed a significant increase in total CoQ10 levels, CoQ10 levels relative to cholesterol, and levels of oxidized and reduced CoQ10 compared to the placebo group. No differences were observed between the two groups for any of the secondary outcomes, including vascular endothelial biomarkers, inflammatory biomarkers, mitochondrial injury biomarkers, or clinical outcomes.

Oral ubiquinol administration successfully increased plasma CoQ10 levels in patients with severe sepsis or septic shock. However, this pilot trial did not demonstrate an improvement in mitochondrial function or clinical outcomes.

This was a pilot trial, and further research is needed to determine if ubiquinol administration can lead to improved clinical outcomes in this patient population.


Effect of Dietary Pyrroloquinoline Quinone Disodium Salt on Cognitive Function in Healthy Volunteers

Daily PQQ supplementation improved multiple aspects of cognitive function in healthy middle-aged to elderly individuals over 12 weeks.

Does daily supplementation with pyrroloquinoline quinone disodium salt (mnemoPQQ®) improve cognitive function in healthy middle-aged to elderly Japanese volunteers?

Hypothesis: Pyrroloquinoline quinone (PQQ) disodium salt will improve cognitive function, including memory, attention, judgment, and cognitive flexibility, in healthy middle-aged to elderly individuals due to its antioxidant activity and effects on mitochondrial activation, nerve cell protection, and amyloid β suppression.

This was a 12-week randomized, double-blind, placebo-controlled, parallel-group clinical investigation. 64 healthy Japanese male and female volunteers aged 40 to less than 80 years were randomly assigned to receive either 21.5 mg/day of mnemoPQQ® or a placebo. Cognitive performance was assessed using Cognitrax as the primary outcome, and the forgetfulness questionnaire (DECO) and Mini-Mental State Examination-Japanese (MMSE-J) as secondary outcomes.

58 subjects completed the study (31 placebo, 27 mnemoPQQ®). The mnemoPQQ® group showed significant improvements in Cognitrax's cognitive function domain scores for "composite memory", "verbal memory", "reaction time", "complex attention", "cognitive flexibility", "executive function", and "motor speed" compared to the placebo group. DECO and MMSE-J scores also significantly improved in the mnemoPQQ® group. No adverse events were observed.

Supplementation with PQQ disodium salt is useful for improving memory, attention, judgment, and overall cognitive function in middle-aged to elderly individuals who perceive age-related forgetfulness.


Resistance training and creatine supplementation on oxidative stress, muscle strength and quality of life in older adults

Resistance training improves antioxidant defense, muscle strength, and quality of life in older adults, and creatine supplementation further enhances muscle strength gains.

What is the effect of resistance training (RT) with creatine monohydrate supplementation (CS) on oxidative stress markers (8-OHdG, MDA, GPX, TAC), muscle strength, and quality of life in older adults?

Hypothesis: The study hypothesized that RT with CS would improve oxidative stress markers, muscle strength, and quality of life in older adults.

Forty-five non-athlete older men and women (mean age 68.1 ± 7.2 years) were randomly assigned to three groups: RT with creatine supplementation (RT + CS), RT with placebo (RT + P), and a control group. The RT protocol involved three sessions per week for 10 weeks. The RT + CS group received 0.1 g/kg body weight of creatine daily, while the RT + P group received an equivalent amount of starch. Fasting blood samples were collected before and after the 10-week intervention to measure oxidative stress markers. Muscle strength and quality of life were also assessed.

After 10 weeks, both training groups (RT + CS and RT + P) showed a significant decrease in MDA and 8-OHDG, and a significant increase in GPX and TAC (p = 0.001 for all). Creatinine levels increased in the RT + CS group (p = 0.014). Quality of life and muscle strength improved in both experimental groups (p = 0.001), with muscle strength changes being more pronounced in the RT + CS group compared to the RT + P group (p < 0.05).

Regular resistance training is a suitable non-pharmacological method to enhance the antioxidant system, muscle strength, and quality of life in older adults. While the role of creatine on the antioxidant system and quality of life in older adults is not definitively established, creatine supplementation alongside RT can significantly increase muscle strength gains.

The study noted that there are no definite findings on the specific role of creatine on the antioxidant system and quality of life in older adults based on this research.


The Additive Effects of Creatine Supplementation and Exercise Training in an Aging Population: A Systematic Review

Creatine supplementation combined with exercise may offer additive benefits for muscle strength, function, and lean mass in older adults, particularly women, but more research is needed for bone, cognition, and optimal dosing.

Does creatine supplementation combined with exercise provide additive improvements in skeletal muscle, bone, and mental health compared to exercise alone in healthy older adults?

Hypothesis: The hypothesis was not explicitly stated, but the review aimed to assess if creatine supplementation combined with exercise results in additive benefits over exercise alone in an aging population.

This systematic review utilized PubMed, CINAHL, and Web of Science databases to identify randomized controlled trials. Studies included creatine supplementation combined with exercise in an aging population, adhering to predetermined inclusion and exclusion criteria. Two independent reviewers screened titles, abstracts, reviewed full-text articles, and performed quality assessments using the Physiotherapy Evidence Database scale.

Seventeen studies were reviewed, suggesting that additive ergogenic creatine effects on upper/lower body strength, functional capacity, and lean mass in older adults may require continuous daily low-dose creatine with at least 12 weeks of resistance training. Potential increases in regional bone mineral density of the femur might require at least 1 year of creatine supplementation combined with moderate resistance training. No additive effects of creatine over exercise alone were found for mental health indices. Benefits were more consistent in older women than men.

Creatine monohydrate is safe for older adults. While creatine with moderate- to high-intensity exercise may improve skeletal muscle health in an aging population, more studies are needed to determine effective dosing and duration for combined effects on bone and cognition.

The abstract does not explicitly state limitations of the systematic review itself, but it highlights the need for additional long-term clinical trials to determine effective dosing and duration paradigms for bone and cognition.


Taurine as a biomarker for aging: A new avenue for translational research

Taurine levels decrease with age, and this deficiency may contribute to aging and age-related diseases, suggesting taurine supplementation could be beneficial.

Does taurine shortage act as a driver and biomarker of aging, and what is its impact on a healthy lifespan?

Hypothesis: The study by Singh et al. proposed that taurine shortage is a driver and biomarker of aging, and that early-life taurine insufficiency is linked to functional abnormalities in organs associated with age-related illnesses.

The authors conducted a lifespan examination of various organisms, including mice, to assess the effects of taurine supplementation. They also analyzed multi-omics datasets (RNA sequencing, metabolomics) across different species after oral taurine supplementation combined with other interventions.

The abstract states that Singh et al. investigated taurine shortage as a driver and biomarker of aging and its impact on a healthy lifespan. It also notes that taurine deficiency in the elderly and the potential benefits of taurine supplements were considered, with a decrease in taurine concentration possibly due to loss of endogenous synthesis. The study analyzed the impacts of taurine supplementation and multi-omics data.

The abstract suggests that taurine deficiency may contribute to the aging process and age-related illnesses, and that taurine supplementation could offer benefits. The study by Singh et al. explored taurine's role as a biomarker and driver of aging.

The abstract does not explicitly state any limitations of the study by Singh et al. or the review itself.


New Functions and Potential Applications of Amino Acids

Amino acids have diverse newly discovered functions with potential applications in digestion, muscle health, sleep, metabolism, immunity, and disease diagnosis.

What are the newly discovered functions and potential applications of various amino acids?

Hypothesis: Not applicable; this review article summarizes existing research on amino acid functions and applications rather than testing a specific hypothesis.

This is a review article summarizing recent discoveries regarding amino acid functions and potential applications. It compiles information on glutamate, branched-chain amino acids (BCAAs), glycine, alanine, glutamine, cystine, and theanine.

Oral glutamate stimulates the cephalic phase response and is recognized by specific systems in the stomach and intestines. Monosodium glutamate enhances gastric secretion in a vagus-dependent manner. BCAAs decrease muscle pain and are considered beneficial for aging. Glycine ingestion before bedtime improves subjective sleep quality. Alanine and glutamine accelerate alcohol metabolism, while cystine and theanine prevent colds. The balance of amino acids in the blood may serve as a diagnostic indicator for disease risk, such as cancer.

Newly discovered functions of amino acids, including their roles in digestion, muscle health, sleep, metabolism, immune function, and disease diagnosis, are expected to offer solutions to various health issues.

This abstract does not describe specific limitations of the reviewed studies or the review itself. It presents a summary of potential benefits without detailing study designs, sample sizes, or statistical significance.


Acetyl-L-carnitine Slows the Progression from Prefrailty to Frailty in Older Subjects: A Randomized Interventional Clinical Trial

Acetyl-L-carnitine supplementation may help slow the progression of prefrailty in older adults by improving cognitive function and physical performance.

Does Acetyl-L-carnitine (ALCAR) affect the progression from prefrailty to frailty in older patients?

Hypothesis: The study aims to evaluate the effect of ALCAR in pre-frail older patients, suggesting a potential beneficial effect.

This was a randomized, observational, double-blind, placebo-controlled study involving 92 subjects. Participants received either oral ALCAR (1.5 g twice daily) or a placebo for 3 months, followed by a 3-month follow-up period. Measurements included C-reactive protein (CRP), serum-free carnitine, acetylcarnitine, Mini-Mental State Examination (MMSE) scores, 6-minute walking distance, and HDL cholesterol.

After treatment, the ALCAR group showed a decrease in CRP and an increase in serum-free carnitine, acetylcarnitine, MMSE scores, and 6-minute walking distance. Compared to the placebo group, the ALCAR group exhibited a decrease in HDL cholesterol and CRP, and an increase in MMSE score and 6-minute walking distance.

ALCAR treatment delays the incidence and severity of degenerative disorders in prefrail older subjects, improving memory and cognitive processes.


Regulation of structural and functional synapse density by L-threonate through intraneuronal magnesium

L-threonate directly increases magnesium inside neurons, leading to more synapses and improved cognitive function, which explains why it's a key component of L-TAMS.

Does L-threonate directly elevate intraneuronal magnesium and regulate synapse density, and why is magnesium alone ineffective for enhancing learning and memory?

Hypothesis: The study aims to understand the unique role of threonate, specifically if it acts directly to elevate intraneuronal Mg2+ and mediates the therapeutic effects of L-TAMS.

The researchers investigated the effects of threonate in cultured hippocampal neurons and human neural stem cell-derived neurons. They measured intracellular Mg2+ concentration, NR2B-containing NMDAR expression, mitochondrial membrane potential (ΔΨm), and functional synapse density. They also examined the role of glucose transporters (GLUTs) in mediating threonate's effects and measured CSF threonate levels after oral L-TAMS treatment.

Threonate is naturally present in CSF, and oral L-TAMS elevated CSF threonate. In cultured hippocampal neurons, threonate treatment directly increased intracellular Mg2+ concentration. Threonate also upregulated NR2B-containing NMDAR expression, boosted mitochondrial membrane potential (ΔΨm), and increased functional synapse density. These effects were unique to threonate and mediated through glucose transporters (GLUTs). Threonate was equally effective at upregulating synapse density in human neural stem cell-derived neurons.

Threonate directly elevates intraneuronal magnesium and regulates structural and functional synapse density through glucose transporters, explaining its essential role in L-TAMS for promoting cognitive abilities.


Effect of omega-3 fatty acids on cardiovascular outcomes: a systematic review and meta-analysis

Omega-3 fatty acids reduce cardiovascular risks, with EPA monotherapy showing greater benefits but also increased risks of bleeding and atrial fibrillation.

What are the effects of omega-3 fatty acids, specifically EPA and EPA+DHA, on fatal and non-fatal cardiovascular outcomes?

Hypothesis: The study aimed to determine the effectiveness of omega-3 FAs on cardiovascular outcomes and examine potential variability between EPA monotherapy and EPA+DHA therapy.

A meta-analysis of 38 randomized controlled trials was conducted, including 149,051 participants. The trials were stratified by EPA monotherapy and EPA+DHA therapy. Random-effects rate ratios (RRs) with 95% confidence intervals were estimated, and the certainty of evidence was rated using GRADE. Key outcomes included cardiovascular mortality, non-fatal cardiovascular outcomes, bleeding, and atrial fibrillation (AF).

Omega-3 FAs were associated with reductions in cardiovascular mortality (RR, 0.93), non-fatal myocardial infarction (MI) (RR, 0.87), coronary heart disease events (CHD) (RR, 0.91), major adverse cardiovascular events (MACE) (RR, 0.95), and revascularization (RR, 0.91). EPA monotherapy showed greater reductions for cardiovascular mortality (RR, 0.82), non-fatal MI (RR, 0.72), and CHD events (RR, 0.73) compared to EPA+DHA (cardiovascular mortality RR, 0.94; non-fatal MI RR, 0.92; CHD events RR, 0.94). Omega-3 FAs increased incident AF (RR, 1.26), and EPA monotherapy was associated with a higher risk of total bleeding (RR, 1.49) and AF (RR, 1.35).

Omega-3 fatty acids reduced cardiovascular mortality and improved cardiovascular outcomes. The cardiovascular risk reduction was more prominent with EPA monotherapy than with EPA+DHA.

The abstract states 'None' for limitations.


Effect of Omega-3 Dosage on Cardiovascular Outcomes: An Updated Meta-Analysis of Interventional Trials

Omega-3 fatty acid supplementation can reduce the risk of certain cardiovascular events, with greater benefits potentially seen at higher doses.

What is the effect of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids on cardiovascular disease (CVD) prevention, and how does dosage influence this effect?

Hypothesis: The study implicitly hypothesizes that EPA/DHA supplementation will reduce the risk of cardiovascular events and that this effect may be dose-dependent.

This study is a random effects meta-analysis and meta-regression of randomized controlled trials (RCTs) involving EPA/DHA supplementation and cardiovascular outcomes. It included RCTs published before August 2019, covering outcomes such as myocardial infarction (MI), coronary heart disease (CHD) events, CVD events, CHD mortality, and fatal MI. The Grading of Recommendations Assessment, Development, and Evaluation framework was used to assess the strength of evidence.

Forty studies with 135,267 participants were included. Supplementation was associated with a reduced risk of MI (RR, 0.87), CHD events (RR, 0.90), fatal MI (RR, 0.65), and CHD mortality (RR, 0.91). No significant reduction was observed for overall CVD events (RR, 0.95). The protective effect was found to be dose-dependent for CVD events and MI.

Supplementation with EPA and DHA is an effective lifestyle strategy for CVD prevention, and the protective effect likely increases with dosage.

The abstract does not explicitly state limitations of the study, but as a meta-analysis, it is dependent on the quality and reporting of the included individual studies.


Oral Alpha Lipoic Acid Treatment for Symptomatic Diabetic Peripheral Neuropathy: A Randomized Double-Blinded Placebo-Controlled Study

Oral alpha-lipoic acid taken twice daily for six months can improve symptoms of diabetic peripheral neuropathy.

Can oral alpha-lipoic acid (ALA) treatment improve symptoms of diabetic peripheral neuropathy (DPN)?

Hypothesis: Oral 600mg ALA twice daily over 6 months will be effective in treating patients with DPN.

This was a prospective, single-center, double-blinded, placebo-controlled study. 200 DPN patients were randomized to receive either oral 600mg ALA twice daily (n=100) or placebo (n=100) for 6 months. Outcomes including vibration perception threshold (VPT), neurological symptom score (NSS), neurological disability score (NDS), and visual analog scale (VAS) for pain were assessed at baseline, 1, 3, and 6 months.

At baseline, there were no significant differences between the groups. In subsequent visits (1, 3, and 6 months), ALA-treated patients showed significantly better results across almost all outcome parameters (NSS, NDS, VAS, VPT). Mild nausea was reported in 6 patients, and no patients discontinued treatment.

Oral 600mg ALA twice daily for 6 months is an effective, safe, and tolerable treatment for DPN.

The study was a single-center design, which may limit the generalizability of the findings.


Effect of adjunctive L-methylfolate 15 mg among inadequate responders to SSRIs in depressed patients

Certain biological and genetic markers may identify depressed patients who are more likely to respond to adjunctive L-methylfolate when SSRIs are insufficient.

Can specific biological and genetic markers predict the antidepressant efficacy of adjunctive L-methylfolate 15 mg in depressed patients who have not adequately responded to SSRIs?

Hypothesis: The study hypothesized that specific biological and genetic markers would influence the antidepressant efficacy of adjunctive L-methylfolate 15 mg compared to placebo in patients with SSRI-resistant major depressive disorder.

This was a double-blind, randomized, placebo-controlled trial using a sequential parallel comparison design. Outpatients with SSRI-resistant MDD received L-methylfolate 15 mg/d for 60 days, or placebo for 30 days followed by L-methylfolate 15 mg/d for 30 days, or placebo for 60 days. The primary response measure was the 28-Item Hamilton Depression Rating Scale (HDRS-28), and the effects of baseline biological and genetic markers on treatment response were evaluated.

Seventy-five patients were enrolled. Patients with specific biological markers (BMI ">=" 30 kg/m², elevated high-sensitivity C-reactive protein or 4-hydroxy-2-nonenal, low S-adenosylmethionine/S-adenosylhomocysteine ratio) and genetic markers at baseline showed significantly greater pooled mean change from baseline on the HDRS-28 with L-methylfolate versus placebo. Most combinations of baseline biological and genetic markers also predicted significantly greater reductions in pooled mean change from baseline in HDRS-28 scores with L-methylfolate versus placebo.

Biomarkers related to inflammation or metabolism and genomic markers associated with L-methylfolate synthesis and metabolism may help identify patients with SSRI-resistant depression who could benefit from adjunctive L-methylfolate 15 mg therapy.

This was a post hoc analysis, and confirmatory studies are needed to validate these findings.


A randomized controlled trial comparing myoinositol with metformin versus metformin monotherapy in PCOS

Adding myoinositol to metformin improves menstrual regularity and quality of life in women with PCOS more than metformin alone, but other hormonal and metabolic markers are not significantly different.

Does a combination of metformin with myoinositol and d-chiro-inositol offer superior benefits compared to metformin monotherapy in women with PCOS?

Hypothesis: The study implicitly hypothesizes that the combination therapy will exert more beneficial effects in PCOS due to the insulin-sensitizing properties of myoinositol and d-chiro-inositol.

This was a 6-month randomized controlled trial involving overweight and obese women with PCOS aged 18-35. Participants were randomized into two groups: 27 received metformin monotherapy, and 26 received metformin with myoinositol and d-chiro-inositol. Various parameters including menstrual cycle duration, anthropometric measures, hormonal profiles, metabolic markers, and quality of life scores were assessed at baseline and after 6 months.

Menstrual cycle regularity improved in both groups, with significantly greater improvement in the myoinositol combination group (p < .001). The PCOS Questionnaire (PCOSQ) score also showed significant improvement in the myoinositol-based therapy group (p < .001). Pregnancy rates were similar between both groups, and no statistically significant differences were observed in other hormonal or metabolic parameters.

Adding myoinositol to metformin provides additional benefits in improving menstrual cycle regularity and quality of life for women with PCOS.

The abstract does not explicitly state limitations of the study.


Comparison of two insulin sensitizers, metformin and myo-inositol, in women with PCOS

Metformin and myo-inositol similarly improve insulin sensitivity, BMI, and menstrual cycles in women with PCOS.

no-difference-cue: "no significant differences" | favorable-cue: "improve"

What are the comparative effects of metformin and myo-inositol on clinical and metabolic features in women with PCOS?

Hypothesis: Insulin-sensitizer agents like metformin and inositols improve endocrine and metabolic aspects of PCOS, and this study aims to compare their effects.

Fifty women with PCOS, insulin resistance (HOMA-IR >2.5) and/or hyperinsulinemia, were randomized to receive either metformin (1500 mg/day) or myo-inositol (4 g/day) for 6 months. Researchers evaluated insulin secretion, BMI, menstrual cycle length, acne, and hirsutism at baseline and after treatment. Insulin resistance was defined as HOMA-IR >2.5, and hyperinsulinemia was defined by AUC for insulin after a glucose load above the laboratory's normal cutoff.

Both treatment groups showed similar improvements. Insulin sensitivity improved in both groups. BMI significantly decreased, and the menstrual cycle normalized in approximately 50% of the women. No significant changes were observed in acne or hirsutism.

Metformin and myo-inositol are both useful in women with PCOS for lowering BMI, ameliorating insulin sensitivity, and improving menstrual cycles, with no significant differences between the two treatments.


Betaine supplementation modulates betaine concentration by MTHFR genotype in healthy active males

Betaine supplementation boosts betaine and lowers homocysteine in active men, with MTHFR genotype potentially influencing betaine levels.

Does betaine supplementation increase betaine concentration and alter amino acid profiles in physically active males, and is this affected by MTHFR genotype and dose?

Hypothesis: Betaine supplementation will increase betaine concentration and alter amino acid profiles in relation to MTHFR genotype and dose in physically active males.

This study used a randomized placebo-controlled cross-over design. Blood samples were collected before and after each supplementation period to analyze serum for amino acid profile, homocysteine, betaine, choline, and trimethylamine N-oxide (TMAO) concentrations. A washout analysis included participants who started with betaine (n=20).

Betaine concentration significantly increased from 4.89 µg/mL to 17.31 µg/mL after supplementation, with a greater increase in MTHFR T-allele carriers compared to CC. Homocysteine concentration decreased from 17.04 µmol/L to 15.44 µmol/L, and TMAO concentrations non-significantly increased from 0.27 µg/ml to 0.44 µg/ml. No differences were found in amino acid profile or choline concentrations. Serum betaine concentrations returned to baseline after a 21-day washout.

Betaine supplementation increased betaine and decreased homocysteine concentrations in healthy active males, but did not affect amino acid profile or choline concentrations. The increase in betaine concentrations may be dependent on MTHFR genotype.

The abstract does not explicitly state limitations, but the non-significant increase in TMAO and the lack of dose-response analysis could be considered implicit limitations.


The Effect of a Multivitamin and Mineral Supplement on Immune Function in Healthy Older Adults: a randomized controlled trial

A multivitamin supplement improved vitamin C and zinc levels and self-reported health in older adults, but did not change measured immune function.

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

Can a multivitamin and mineral (MVM) supplement improve immune function in healthy older adults?

Hypothesis: Taking a multi-vitamin and mineral supplement (MVM) could improve immune function in individuals 55 and older.

Healthy older adults were randomized to receive either an MVM supplement (RedoxonVI) or an inactive placebo daily for 12 weeks. Researchers measured blood mineral and vitamin status (vitamin C, zinc, vitamin D), immune function (bacterial killing, neutrophil phagocytic activity, reactive oxygen species), immune status (salivary IgA, plasma cytokine/chemokine levels), and self-reported health status before and after treatment.

MVM supplementation improved blood vitamin C and zinc status, as well as self-reported health status. However, it did not alter measures of immune function, immune status, or vitamin D levels.

MVM supplementation may benefit healthy older adults by improving vitamin C and zinc status and self-reported health, but it did not show changes in measured immune function or status in this study.

The study suggests that further development of functional assays and larger study populations are needed to better detect specific changes in immune function after supplementation in healthy older adults.


Effect of Zinc Supplementation in Children on Diarrhea Attacks: A Randomized Controlled Trial

Daily zinc supplementation for four months reduced the occurrence and severity of diarrhea in young children.

Does daily zinc supplementation for 4 months affect the incidence and severity of diarrheal morbidity in children aged 6 months to less than 5 years old?

Hypothesis: The study aims to assess the effect of daily zinc supplements on the incidence and severity of diarrheal morbidity in children.

A randomized controlled trial was conducted on 140 apparently healthy children aged 6 months to less than 5 years old. Children were randomly assigned to either a zinc supplementation group (70 children) or a placebo group (70 children) for 4 months. Serum zinc levels were measured at baseline, and a questionnaire was used during follow-up to record the occurrence of diarrhea.

The mean age of participants was 25.26 ± 15.7 months, and the mean baseline serum zinc was 51.08 μg/dL, with 70% of children having low baseline serum zinc. The cumulative incidence of diarrhea, the number of diarrhea episodes per child, and the frequency of stools per day significantly decreased in the zinc group. The risk ratio for diarrhea was 0.79 (95% CI: 0.64 to 0.97).

Daily zinc supplementation for 4 months reduced the incidence and severity of diarrhea in children.


Selenium and Coenzyme Q Intervention Prevents Telomere Attrition, with Association to Reduced Cardiovascular Mortality

Selenium and coenzyme Q10 supplementation may help preserve telomere length and reduce cardiovascular mortality in older adults with low selenium.

favorable-cue: "associated with reduced"

Does long-term supplementation with combined selenium and coenzyme Q10 prevent telomere attrition and reduce cardiovascular mortality in elderly individuals with low selenium levels?

Hypothesis: The study aimed to determine if selenium and coenzyme Q10 supplementation could prevent telomere shortening and decrease cardiovascular mortality.

This was an explorative sub-study of a double-blind, placebo-controlled, randomized trial. 118 Swedish citizens aged 70-80 years with low selenium levels were included. Participants received either active treatment (selenium and coenzyme Q10) or placebo for 4 years, with a 10-year follow-up. Leukocyte telomere length (LTL) was measured at baseline and after 42 months using PCR.

At 42 months, the active treatment group showed less shortening of LTL (+0.019) compared to the placebo group (-0.129), a significant difference (p = 0.02). Analyzing individual changes in LTL also showed a significant difference (p < 0.001). Subjects who died later had significantly shorter LTL at 42 months (0.791) than survivors (0.941) (p = 0.01), and there was a significant difference in LTL change based on cardiovascular mortality (p = 0.03).

Supplementation with selenium and coenzyme Q10 was associated with the preservation of leukocyte telomere length, which in turn was associated with reduced cardiovascular mortality.


Selenium and coenzyme Q10 interrelationship in cardiovascular diseases

Supplementing with selenium and coenzyme Q10 may improve cardiovascular outcomes in elderly individuals, potentially by enhancing antioxidant capacity.

What is the potential role of selenium deficiency and selenium intervention in atherosclerotic heart disease, and how does it interrelate with coenzyme Q10?

Hypothesis: Selenium deficiency may lead to reduced anti-oxidative capacity, influencing the prognosis of atherosclerotic disease. Combining selenium and coenzyme Q10 may offer a theoretical advantage in intervention due to their anti-oxidative properties.

This is a short review discussing the potential role of selenium deficiency and intervention trials in atherosclerotic heart disease. It also presents the interrelationship between selenium and coenzyme Q10 and discusses clinical results from an intervention study using both substances in an elderly population.

Selenium intake in Europe is often at the lower margin of recommendations, potentially leading to deficient anti-oxidative capacity in conditions like atherosclerotic disease. Increased oxidative stress is demonstrated in ischemic heart disease and heart failure. A clinical intervention study in an elderly population using both selenium and coenzyme Q10 showed a reduction in cardiovascular mortality, improved cardiac function by echocardiography, and lower NT-proBNP concentrations in the active treatment group compared to placebo.

Selenium deficiency may contribute to atherosclerotic disease due to reduced anti-oxidative capacity. Supplementation with both selenium and coenzyme Q10 in an elderly population demonstrated benefits including reduced cardiovascular mortality, improved cardiac function, and lower myocardial wall tension.

The review does not specify the exact details, sample sizes, or statistical significance of the discussed intervention studies. It also does not quantify the observed reductions or improvements.


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

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

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

Does L-carnitine reduce morbidity and mortality in patients who have experienced an acute myocardial infarction?

Hypothesis: The study implicitly hypothesizes that L-carnitine, compared to placebo or control, will reduce adverse cardiovascular outcomes such as mortality, ventricular arrhythmias, angina, heart failure, and reinfarction in patients with acute myocardial infarction.

A systematic review and meta-analysis was conducted, including 13 controlled trials with a total of 3629 participants. The researchers searched Ovid MEDLINE, PubMed, and Embase databases for studies published between May 1, 2012, and August 31, 2012. The effects of L-carnitine versus placebo or control on mortality, ventricular arrhythmias (VAs), angina, heart failure, and reinfarction were evaluated.

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

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

The abstract does not explicitly state limitations of the meta-analysis, but it suggests that further large randomized controlled trials are warranted, implying a need for more robust evidence.


Magnesium Supplementation and Blood Pressure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Magnesium supplementation can help lower blood pressure, especially in people with high blood pressure or low magnesium levels, but more research is needed due to study variability.

What is the effect of magnesium supplementation on blood pressure in both hypertensive and normotensive populations?

Hypothesis: The study aimed to explore the relationship between magnesium supplementation and blood pressure.

A systematic review and meta-analysis of 38 randomized controlled trials, involving 2709 participants, was conducted. Studies had a duration of at least 4 weeks, with elemental magnesium doses ranging from 82.3 mg to 637 mg (median 365 mg) and a median intervention period of 12 weeks. Mean differences of changes in blood pressure were calculated using a random effects meta-analysis, and a cubic spline regression model was used for dose-response analysis.

Magnesium supplementation reduced systolic blood pressure by -2.81 mm Hg and diastolic blood pressure by -2.05 mm Hg overall. Greater reductions in systolic blood pressure were observed in hypertensive individuals on BP-lowering medication (-7.68 mm Hg) and individuals with hypomagnesemia (-5.97 mm Hg). Diastolic blood pressure also saw greater reductions in these groups (-2.96 mm Hg and -4.75 mm Hg, respectively). No statistically significant effect was found in normotensive groups, and no dose-response relationship was identified.

Magnesium supplementation has a beneficial effect on reducing blood pressure, particularly in populations with hypertension and hypomagnesemia. However, the high heterogeneity across studies suggests that these effects should be interpreted with caution.

The study identified high heterogeneity across the included trials. Further larger, well-designed studies are needed to assess higher magnesium doses and refine the dose-response relationship, as well as to identify optimal supplementation strategies for specific subpopulations.


The Effects of Magnesium Supplementation on Blood Pressure Among Type 2 Diabetes Patients: a meta-analysis

Magnesium supplementation can help lower blood pressure in people with type 2 diabetes, especially with higher doses or longer durations.

Does magnesium supplementation affect blood pressure and obesity measures in patients with type 2 diabetes mellitus?

Hypothesis: The study aimed to evaluate the effects of magnesium supplementation on blood pressure and obesity measures in type 2 diabetes patients.

A meta-analysis of randomized clinical trials (RCTs) was conducted by searching major electronic databases (Web of Science, Cochrane library, PubMed, Scopus) up to October 15, 2019. Outcomes were pooled using a random-effects model and expressed as weighted mean differences (WMD) with 95% confidence intervals (CI). Heterogeneity, sensitivity analysis, and publication bias were also assessed.

Pooling five RCTs showed that magnesium supplementation did not significantly affect body weight (WMD: -0.01 kg), BMI (WMD: -0.07), or waist circumference (WMD: 0.12). However, pooling seven RCTs showed a significant reduction in systolic blood pressure (WMD: -5.78 mmHg) and diastolic blood pressure (WMD: -2.50 mmHg). Subgroup analysis indicated that magnesium supplementation for more than 12 weeks, at doses higher than 300 mg/day, or in inorganic forms, significantly decreased both systolic and diastolic blood pressure.

Magnesium supplementation has beneficial effects on blood pressure in type 2 diabetes patients, independent of body weight status.

The study suggests that further investigations are needed to provide more reliable evidence.


beta-alanine supplementation to improve exercise capacity and performance: a systematic review and meta-analysis

"beta"-alanine supplementation can improve exercise capacity and performance, especially for exercise lasting 0.5-10 minutes and when co-supplemented with sodium bicarbonate.

What are the effects of "beta"-alanine supplementation on exercise capacity and performance?

Hypothesis: The study aimed to systematically review and meta-analyze existing evidence to determine the effects of "beta"-alanine supplementation on exercise capacity and performance.

This systematic review and meta-analysis followed PRISMA guidelines. Researchers searched PubMed, Google Scholar, and Web of Science for double-blinded, placebo-controlled studies on chronic "beta"-alanine supplementation and exercise measures in healthy participants. Cross-over designs were excluded. A 3-level mixed effects model was used to analyze effect sizes from 70 exercise measures across 40 studies and 1461 participants.

A significant overall effect size of 0.18 (95% CI 0.08 to 0.28) was found for "beta"-alanine supplementation. Exercise duration significantly moderated effect sizes (p=0.004), as did exercise type within the 0.5-10 minute timeframe (p=0.013). Greater effect sizes were observed for exercise capacity (0.4998) compared to performance (0.1078) in this timeframe. Training status, intermittent/continuous exercise, and total "beta"-alanine ingested did not significantly moderate effects. Co-supplementation with sodium bicarbonate showed the largest effect size (0.43).

"beta"-alanine supplementation has a significant overall effect on exercise capacity and performance, with exercise duration and type being significant modifying factors. These findings can help individuals make informed decisions about using "beta"-alanine based on their exercise modality.


Effect of Beta-Alanine Supplementation on Maximal Intensity Exercise in Trained Young Males: A Meta-Analysis

Beta-alanine supplementation can enhance maximal exercise performance in trained young men, especially with specific durations and dosages.

Does beta-alanine supplementation improve maximal intensity exercise performance in trained young males?

Hypothesis: Beta-alanine supplementation will improve exercise performance by buffering hydrogen ions and delaying fatigue through increased intramuscular carnosine synthesis.

This systematic review and meta-analysis searched six databases for randomized, double-blinded, placebo-controlled trials published up to August 10, 2023. Included studies investigated chronic beta-alanine supplementation in trained males aged 18-40 years, evaluating maximal or supramaximal intensity exercise lasting 0.5-10 minutes. A total of 18 studies, 18 exercise protocols, and 15 outcome measures from 331 participants were analyzed.

A significant overall effect size of 0.39 (95% CI [0.09, 0.69], p = .01) was observed in favor of beta-alanine supplementation. Significant effects were noted at 4 weeks of supplementation (effect size 0.34, 95% CI [0.02, 0.67], p = .04), for maximal efforts lasting 4-10 minutes (effect size 0.55, 95% CI [0.07, 1.04], p = .03), and with a high beta-alanine dosage of 5.6-6.4 g per day (effect size 0.35, 95% CI [0.09, 0.62], p = .009).

Beta-alanine supplementation significantly improves maximal intensity exercise performance in trained young males, particularly with 4 weeks of supplementation, for efforts lasting 4-10 minutes, and at dosages of 5.6-6.4 g per day.

The abstract does not explicitly state limitations of the meta-analysis itself, but rather provides insights for future research and practical applications.


The effect of menaquinone-7 supplementation on vascular calcification in patients with diabetes: a randomized controlled trial

Menaquinone-7 supplementation did not reduce vascular calcification in patients with type 2 diabetes and cardiovascular disease, and may have slightly increased active calcification.

Does menaquinone-7 supplementation decrease vascular calcification in patients with type 2 diabetes and cardiovascular disease?

Hypothesis: Menaquinone-7 supplementation, compared to placebo, will decrease vascular calcification in people with type 2 diabetes and known cardiovascular disease.

This was a double-blind, randomized, placebo-controlled trial. Participants with type 2 diabetes and cardiovascular disease were assigned to receive either 360 µg/d menaquinone-7 (MK-7) or placebo for 6 months. Femoral arterial calcification was measured at baseline and 6 months using 18F-NaF PET scans (target-to-background ratios, TBRs) for active calcification and conventional CT scans for calcification mass. Dephosphorylated-uncarboxylated matrix Gla protein (dp-ucMGP) concentrations were also measured.

35 patients were assigned to the MK-7 group (33 completed) and 33 to the placebo group (27 completed). After 6 months, TBR tended to increase in the MK-7 group compared with placebo (0.25; P = 0.06), though not significantly. Log-transformed CT calcification mass did not increase in the intervention group compared with placebo (0.50; P = 0.18). MK-7 supplementation significantly reduced dp-ucMGP compared with placebo (-205.6 pmol/L). No adverse events were reported.

Menaquinone-7 supplementation tended to increase active calcification as measured by 18F-NaF PET activity, but had no effect on conventional CT calcification. Further research is needed to interpret 18F-NaF PET activity.

The study found a non-significant trend towards increased active calcification with MK-7, and the interpretation of 18F-NaF PET activity requires further investigation.


Effect of vitamin K supplementation on arterial stiffness in vitamin K-deficient kidney transplant recipients

Vitamin K supplementation in kidney transplant recipients improved vitamin K status and prevented arterial stiffness progression, but did not change calcification propensity.

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

Does vitamin K supplementation affect serum calcification propensity and arterial stiffness in vitamin K-deficient kidney transplant recipients?

Hypothesis: Vitamin K deficiency likely contributes to progressive vascular calcification and stiffness in kidney transplant recipients, suggesting that supplementation might improve these outcomes.

This was a single-center, randomized, double-blind, placebo-controlled trial involving 40 vitamin K-deficient kidney transplant recipients. Participants were randomized 1:1 to receive either vitamin K2 (menaquinone-7, 360 μg/day) or placebo for 12 weeks. The primary endpoint was serum calcification propensity (T50), and secondary endpoints included arterial stiffness (pulse wave velocity [PWV]) and vitamin K status (dp-ucMGP).

Vitamin K supplementation did not significantly affect calcification propensity (change in T50 vs baseline +2.3 ± 27.4 minutes for vitamin K vs +0.8 ± 34.4 minutes for placebo; P= .88). However, it prevented the progression of PWV (change vs baseline -0.06 ± 0.26 m/s for vitamin K vs +0.27 ± 0.43 m/s for placebo; P= .010). Vitamin K status significantly improved with supplementation (change in dp-ucMGP vs baseline -385 pmol/L for vitamin K vs +39 pmol/L for placebo; P< .001), though most patients remained vitamin K-deficient.

Vitamin K supplementation did not alter serum calcification propensity but prevented the progression of arterial stiffness in vitamin K-deficient kidney transplant recipients. This suggests that vitamin K may have vascular effects independent of calciprotein particles.

The study was a single-center trial and, despite improved vitamin K status, most patients remained vitamin K-deficient, indicating that the dose or duration might not have been sufficient to fully correct the deficiency or impact calcification propensity. The abstract also suggests the need for longer-term intervention studies.


Effect of carnosine on lipid profile, fasting blood glucose, HbA1C and insulin resistance: a meta-analysis of randomized controlled trials

Carnosine supplementation may help lower HbA1C levels, but it does not appear to impact other markers of glucose metabolism or lipid profile.

Does carnosine supplementation affect lipid profile, fasting blood glucose, HbA1C, and insulin resistance?

Hypothesis: Carnosine supplementation may improve glucose disorders and dyslipidemia.

A meta-analysis of randomized controlled trials (RCTs) was conducted by searching MEDLINE/PubMed, Scopus, and Web of Science up to June 2019. The search used Medical Subject Heading and keywords. Combined effect sizes were calculated as weighted mean difference (WMD) using a random-effects model, and heterogeneity was assessed with Cochran's Q test and I .

Four RCTs, involving 184 participants, were analyzed. Carnosine intervention significantly reduced HbA1C levels (WMD: -0.92 %, 95 % CI: -1.20, -0.63, I:69 %). However, combined results from four studies with 183 participants showed no significant reduction in triglycerides (WMD: -14.46 mg/dl, 95 % CI: -29.11, 0.19, I:94 %). No significant changes were observed for HOMA-IR, Cholesterol, fasting blood sugar, or HDL-C.

Carnosine supplementation decreases HbA1C but does not significantly affect HOMA-IR, Cholesterol, fasting blood sugar, triglycerides, or HDL-C.

The study notes that future research with larger sample sizes, varied carnosine doses, and population-specific subgroups is needed to confirm and strengthen these findings.


Physiological Bases for the Superiority of Apolipoprotein B as a Marker of Cardiovascular Risk

ApoB is a better indicator of heart disease risk than LDL-C because it directly measures the number of harmful particles, which is more accurate than measuring only the cholesterol within them.

What are the physiological mechanisms that make apolipoprotein B (apoB) a superior marker of cardiovascular risk compared to low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol?

Hypothesis: The review posits that specific physiological mechanisms related to the nature, number, and cholesterol content of atherogenic apoB lipoprotein particles explain why apoB is a more accurate marker of cardiovascular risk.

This is a narrative review that outlines the physiological mechanisms. It discusses the nature and relative numbers of different apoB particles, the mechanisms governing the number of very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) particles, and the mechanisms governing the cholesterol mass within these particles. It also briefly outlines major apoB dyslipoproteinemias.

The review explains that LDL particles are typically the primary determinants of cardiovascular risk. It details how concentrations of triglycerides and LDL-C can obscure this relationship. It further clarifies that the total number of apoB particles, except in cases of dysbetalipoproteinemia, determines cardiovascular risk. The review highlights that the discordance between the cholesterol mass within apoB particles (measured as LDL-C or non-HDL-C) and the actual number of apoB particles (measured as apoB) is responsible for apoB's superior predictive power.

Apolipoprotein B (apoB) is a more accurate marker of cardiovascular risk than LDL-C or non-high-density lipoprotein cholesterol due to specific physiological mechanisms related to the number and cholesterol content of atherogenic apoB lipoprotein particles. This review provides a physiological framework for healthcare providers to understand this superiority.

This is a review article and does not present new experimental data or a meta-analysis of existing studies. It focuses on explicating known physiological mechanisms.


Non-HDL-cholesterol and apolipoprotein B compared with LDL-cholesterol in cardiovascular disease risk assessment

Non-HDL-cholesterol and apolipoprotein B may be better indicators of heart disease risk than LDL-cholesterol, especially in certain individuals.

What are the measurement, potential role, utility, and current status of non-HDL-cholesterol and apolipoprotein B compared with LDL-cholesterol in atherosclerotic cardiovascular disease (ASCVD) risk assessment?

Hypothesis: The authors hypothesize that non-HDL-cholesterol and apolipoprotein B (apoB) may be superior to LDL-cholesterol in predicting ASCVD risk, particularly in certain patient populations.

This study is a review of existing literature, examining the measurement, potential role, utility, and current status of non-HDL-cholesterol and apoB in comparison to LDL-cholesterol for ASCVD risk assessment.

LDL-cholesterol is a primary therapeutic target for ASCVD, but its estimation via the Friedewald equation has limitations, and direct measures are not standardized. Non-HDL-cholesterol includes remnant cholesterol and is independent of triglyceride variability, but it is affected by non-specificity bias of direct HDL-cholesterol methods. ApoB measures the number of atherogenic lipoproteins, and its methods are standardized, though it incurs an additional cost. Non-HDL-cholesterol and apoB are more accurate than LDL-cholesterol in individuals with hypertriglyceridemia, in non-fasting samples, and in those with very low LDL-cholesterol. Evidence suggests non-HDL-cholesterol and apoB are superior to LDL-cholesterol in predicting ASCVD risk and are designated as secondary targets in some guidelines.

Non-HDL-cholesterol and apolipoprotein B offer advantages over LDL-cholesterol in ASCVD risk assessment, particularly in specific patient groups, and accumulating evidence supports their superiority in predicting ASCVD risk.

The review does not present new experimental data or specific quantitative comparisons from a single study, but rather synthesizes existing evidence.


Lipoprotein(a) and Cardiovascular Disease

High lipoprotein(a) levels are causally linked to increased cardiovascular disease risk, but more research is needed to confirm treatment benefits.

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

Does high lipoprotein(a) (Lp(a)) concentration causally increase the risk of ischemic cardiovascular disease, and does it represent an unmet medical need?

Hypothesis: The review implicitly hypothesizes that high Lp(a) concentrations are causally linked to increased cardiovascular disease risk and may represent an unmet medical need requiring treatment.

This is a narrative review summarizing evidence from mechanistic, observational, and large genetic epidemiologic studies regarding the causality of high Lp(a) concentrations in cardiovascular disease. It also discusses Lp(a) measurement methods and future treatment options.

Evidence from mechanistic, observational, and genetic studies supports a causal role of Lp(a) in the development of cardiovascular disease, including coronary heart disease, peripheral arterial disease, aortic valve stenosis, and likely ischemic stroke. High Lp(a) concentrations predict 2- to 3-fold increases in risk for myocardial infarction, peripheral arterial disease, and aortic valve stenosis. High Lp(a) concentrations are present in 10%-20% of the population, affecting an estimated >1 billion individuals worldwide.

High lipoprotein(a) concentrations are causally linked to an increased risk of cardiovascular diseases such as myocardial infarction, peripheral arterial disease, and aortic valve stenosis. Standardized Lp(a) measurements are crucial, and randomized cardiovascular outcome trials are necessary to confirm causality and evaluate the clinical benefit of Lp(a)-lowering therapies.

The review highlights the need for randomized cardiovascular outcome trials to provide final evidence of causality and assess the clinical benefit of novel Lp(a) lowering therapies, indicating that current evidence, while strong, is not definitive for treatment decisions.


Elevated Lipoprotein(a) and Risk of Atrial Fibrillation

Elevated lipoprotein(a) is associated with an increased risk of atrial fibrillation, partly independent of its effects on atherosclerotic cardiovascular disease.

Does elevated lipoprotein(a) (Lp[a]) increase the risk of atrial fibrillation (AF), and is this association independent of atherosclerotic cardiovascular disease (ASCVD)?

Hypothesis: The study investigated the role of Lp(a) in AF and whether it is independent of ASCVD.

The study analyzed measured and genetically predicted Lp(a) levels in relation to 20,432 cases of incident AF in the UK Biobank (N = 435,579). Mendelian randomization analyses were also conducted using summary-level data for AF from publicly available genome-wide association studies (N = 1,145,375).

In the UK Biobank, each 50 nmol/L increase in Lp(a) was associated with an increased risk of incident AF (measured Lp[a]: HR: 1.03; genetically predicted Lp[a]: OR: 1.03). Mendelian randomization analyses replicated this effect (OR: 1.04 per 50 nmol/L Lp[a] increase). Only 39% of Lp(a) risk was mediated through ASCVD, suggesting an independent influence on AF.

The findings suggest that Lp(a) is a potential causal mediator in the development of AF, with effects extending across myocardial tissues and partly independent of its known effects on ASCVD. Ongoing clinical trials for Lp(a)-lowering therapies should evaluate effects on AF prevention.


C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women

Adding C-reactive protein to standard lipid screening can better identify postmenopausal women at risk for cardiovascular events.

Can measuring markers of inflammation improve the prediction of cardiovascular event risk?

Hypothesis: Measurement of markers of inflammation, in addition to traditional risk factors, will improve the prediction of cardiovascular event risk.

A prospective, nested case-control study was conducted among 28,263 apparently healthy postmenopausal women over a mean follow-up of three years. Researchers assessed the risk of cardiovascular events associated with baseline levels of various markers, including high-sensitivity C-reactive protein (hs-CRP), serum amyloid A, interleukin-6, soluble intercellular adhesion molecule type 1 (sICAM-1), homocysteine, and lipid measurements. Cardiovascular events included death from coronary heart disease, nonfatal myocardial infarction or stroke, or the need for coronary-revascularization procedures.

Hs-CRP was the strongest univariate predictor of cardiovascular events, with a relative risk of 4.4 for women in the highest versus lowest quartile. Other significant univariate predictors included serum amyloid A (3.0), sICAM-1 (2.6), interleukin-6 (2.2), homocysteine (2.0), total cholesterol (2.4), LDL cholesterol (2.4), apolipoprotein B-100 (3.4), HDL cholesterol (0.3), and the ratio of total cholesterol to HDL cholesterol (3.4). Prediction models incorporating inflammation markers and lipids were significantly better than lipid-only models (P<0.001). Hs-CRP and serum amyloid A were significant predictors even in women with LDL cholesterol below 130 mg/dL. In multivariate analyses, only hs-CRP (relative risk 1.5) and the ratio of total cholesterol to HDL cholesterol (relative risk 1.4) independently predicted risk.

Adding C-reactive protein measurement to lipid-based screening may improve the identification of individuals at risk for cardiovascular events.

The study was conducted in apparently healthy postmenopausal women, which may limit generalizability to other populations. The follow-up period was a mean of three years, which might not capture long-term risks.


Inflammation, Cholesterol, Lipoprotein(a), and 30-Year Cardiovascular Outcomes in Women

Measuring inflammation and cholesterol markers can predict long-term cardiovascular risk in women, supporting earlier and longer-term prevention strategies.

How useful are high-sensitivity C-reactive protein (CRP), low-density lipoprotein (LDL) cholesterol, and lipoprotein(a) levels for predicting cardiovascular risk over 30 years in women?

Hypothesis: The study aimed to determine if baseline levels of high-sensitivity CRP, LDL cholesterol, and lipoprotein(a) can predict long-term cardiovascular risk in women, given their established utility in shorter-term predictions and the importance of early-life intervention.

This study measured baseline levels of high-sensitivity CRP, LDL cholesterol, and lipoprotein(a) in 27,939 initially healthy U.S. women, who were then followed for 30 years. The primary end point was a first major adverse cardiovascular event, a composite of myocardial infarction, coronary revascularization, stroke, or cardiovascular death. Adjusted hazard ratios and 95% confidence intervals were calculated across quintiles of each biomarker, along with 30-year cumulative incidence curves adjusted for age and competing risks.

During 30 years, 3662 first major cardiovascular events occurred among participants with a mean baseline age of 54.7 years. Increasing baseline levels across quintiles of high-sensitivity CRP, LDL cholesterol, and lipoprotein(a) all predicted 30-year risks. The adjusted hazard ratios for the primary end point comparing the top to the bottom quintile were 1.70 for high-sensitivity CRP, 1.36 for LDL cholesterol, and 1.33 for lipoprotein(a). Each biomarker independently contributed to overall risk, and models combining all three biomarkers showed the greatest risk spread.

A single combined measure of high-sensitivity CRP, LDL cholesterol, and lipoprotein(a) levels at baseline in initially healthy U.S. women is predictive of incident cardiovascular events over a 30-year period. These findings support extending primary prevention strategies for atherosclerotic events beyond traditional 10-year risk estimates.


Omega-3 fatty acids and mortality in patients referred for coronary angiography

Higher levels of omega-3 fatty acids EPA and DHA in red blood cells are linked to lower all-cause and cardiovascular mortality in patients undergoing coronary angiography.

Do omega-3 fatty acids protect from cardiovascular disease mortality?

Hypothesis: The study hypothesized that erythrocyte omega-3 fatty acids would be associated with mortality in patients referred for coronary angiography.

Erythrocyte omega-3 fatty acid proportions were measured at baseline in 3259 participants of the Ludwigshafen Risk and Cardiovascular Health Study (LURIC) using the HS-Omega-3 Index method. Cox proportional hazards regression was used to investigate associations of omega-3 fatty acid proportions with mortality.

During a median follow-up of 9.9 years, 975 patients (29.9%) died, with 614 patients (18.8%) dying from cardiovascular causes. Proportions of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were inversely associated with all-cause and cardiovascular mortality, even after adjusting for conventional cardiovascular risk factors. The strongest association was for EPA, with a hazard ratio (HR) of 0.89 (0.83-0.96) per increase of one standard deviation. Evidence for a non-linear relationship between EPA and mortality was also observed.

EPA and DHA were associated with reduced mortality in the LURIC study, independent of other risk factors. The association between EPA and mortality appeared to be non-linear.

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


Glycated haemoglobin, diabetes, and mortality in men in the EPIC-Norfolk cohort

Higher HbA1c levels are continuously linked to increased mortality risk in men, even in those without diagnosed diabetes, suggesting a need for broader preventive efforts.

Does glycated haemoglobin (HbA1c) concentration predict death from cardiovascular and all causes in men?

Hypothesis: The study aims to examine the value of HbA1c as a predictor of mortality.

This was a prospective population study conducted within the Norfolk cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Norfolk). It included 4662 men aged 45-79 years who had baseline HbA1c measurements between 1995-1997 and were followed up until December 1999. Mortality from all causes, cardiovascular disease, ischaemic heart disease, and other causes was assessed.

Men with known diabetes had increased mortality from all causes (relative risk 2.2), cardiovascular disease (relative risk 3.3), and ischaemic disease (relative risk 4.2) compared to men without known diabetes. This increased risk in diabetic men was largely explained by HbA1c concentration. HbA1c was continuously related to subsequent all-cause, cardiovascular, and ischaemic heart disease mortality across the entire population, with the lowest rates observed in those with HbA1c concentrations below 5%. A 1% increase in HbA1c was associated with a 28% increase in the risk of death, independent of other risk factors. Even after excluding men with known diabetes, HbA1c >=7%, or a history of myocardial infarction or stroke, this effect remained (relative risk 1.46). While 18% of the population excess mortality risk associated with HbA1c >=5% occurred in men with diabetes, 82% occurred in men with concentrations of 5%-6.9%.

Glycated haemoglobin concentration appears to explain most of the excess mortality risk associated with diabetes in men and acts as a continuous risk factor across the entire population distribution. Preventive strategies should consider not only individuals with established diabetes but also the potential to reduce the population distribution of HbA1c through behavioral interventions.


Contrasting associations of insulin resistance with diabetes, cardiovascular disease and all-cause mortality in the elderly: PROSPER

In older adults, insulin resistance predicts diabetes but does not significantly predict cardiovascular disease or mortality.

Does insulin resistance, measured by fasting insulin and HOMA-IR, predict incident cardiovascular disease (CVD) and diabetes in older people, and do these associations differ in strength?

Hypothesis: Insulin resistance is commonly proposed as a precursor to both type 2 diabetes and cardiovascular disease.

The study used data from the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) cohort, specifically 4,742 older individuals (70-82 years) without diabetes at baseline who had HOMA-IR measurements. Participants were followed for 3.2 years for incident diabetes and 8.6 years for all-cause mortality, CHD deaths, and fatal/non-fatal CVD events. Cause-specific Cox proportional-hazards models were fitted using multivariable models to assess associations.

Higher HOMA-IR was associated with incident diabetes, with a hazard ratio (HR) of 4.80 (95% CI 3.14, 7.33) when comparing extreme thirds after adjustment. However, HOMA-IR in the top third was not associated with all-cause mortality (HR 1.02, 95% CI 0.90, 1.17), CHD mortality (HR 1.03, 95% CI 0.79, 1.36), or fatal/non-fatal CVD (HR 0.94, 95% CI 0.74, 1.20). Similar results were observed when fasting insulin was used as the exposure.

The data support insulin resistance as a predictor of diabetes in later life. However, this pathway appears to be of negligible importance to cardiovascular disease outcomes in the elderly.

The abstract does not explicitly state limitations beyond the scope of the study, but it implies that the findings regarding CVD in the elderly might be surprising given common proposals.


Total plasma homocysteine level and risk of cardiovascular disease: a meta-analysis of prospective cohort studies

Higher homocysteine levels are moderately associated with an increased risk of cardiac events and ischemic stroke.

Does total plasma homocysteine level increase the risk of cardiovascular disease?

Hypothesis: The role of homocysteine as a cardiovascular disease risk factor is controversial, with conflicting results from different study types.

This meta-analysis synthesized data from 14 published prospective cohort studies. Average relative risks (ARRs) were calculated using fixed and random effect models. The study also assessed for publication and selection bias and the impact of individual studies on the ARR.

No evidence of publication bias (P =.62) or heterogeneity (P =.56) was found. The ARR for cardiac events was 1.49 (95% CI: 1.31-1.70), and for ischemic stroke, it was 1.37 (95% CI: 0.99-1.99). Age and duration of follow-up did not significantly alter these ARRs.

Hyperhomocysteinemia is associated with a moderate increase in the risk of a first cardiovascular event, independent of age and follow-up duration.

The abstract does not explicitly state limitations of the meta-analysis itself, beyond acknowledging the prior controversy and potential for reverse causality bias in case-control studies.


Time-dependent associations between iron and mortality in hemodialysis patients

Maintaining specific iron levels and administering moderate intravenous iron doses may improve survival in hemodialysis patients, but high ferritin levels are often confounded by malnutrition-inflammation.

What is the independent association between iron indices or administered intravenous iron and survival in maintenance hemodialysis (MHD) patients, considering their time-varying nature?

Hypothesis: The associations between moderately high levels of serum ferritin, iron, iron saturation ratio, or administered intravenous iron and all-cause and cardiovascular death in MHD patients are confounded by the time-varying effects of malnutrition-inflammation-cachexia syndrome (MICS).

Time-dependent Cox regression models were used to analyze prospectively collected data from a 2-year historical cohort (July 2001 to June 2003) of 58,058 MHD patients from DaVita dialysis clinics in the United States. Adjustments were made for case mix, administered intravenous iron and erythropoietin doses, and surrogates of MICS.

Serum ferritin levels between 200 and 1200 ng/ml, serum iron levels between 60 and 120 microg/ml, and iron saturation ratio between 30 and 50% were associated with the lowest all-cause and cardiovascular death risks. Administered intravenous iron up to 400 mg/mo was associated with improved survival, while doses >400 mg/mo tended to be associated with higher death rates. The association between serum ferritin levels >800 ng/ml and mortality appeared to be mostly due to MICS confounding.

Optimal ranges for serum ferritin (200-1200 ng/ml), serum iron (60-120 microg/ml), and iron saturation ratio (30-50%) are associated with the lowest mortality risks in MHD patients. Intravenous iron doses up to 400 mg/mo are linked to improved survival, but higher doses may increase death rates. The link between high ferritin (>800 ng/ml) and mortality is largely explained by MICS.

The study design cannot definitively determine if the observed associations between moderate doses of intravenous iron and improved survival are causal or due to selection bias by indication. Clinical trials are needed to clarify this.


Thyroid antibody status, subclinical hypothyroidism, and the risk of coronary heart disease

Thyroid antibody status does not independently predict coronary heart disease risk in individuals with subclinical hypothyroidism.

Does thyroid autoimmunity, specifically the presence of thyroid peroxidase antibodies (TPOAbs), independently affect the risk of coronary heart disease (CHD) in individuals with subclinical hypothyroidism?

Hypothesis: The study aimed to compare the CHD risk in subclinical hypothyroidism with and without TPOAbs to determine if thyroid autoimmunity independently affects CHD risk.

A MEDLINE and EMBASE search from 1950 to 2011 was conducted to identify prospective cohorts reporting baseline thyroid function, antibodies, and CHD outcomes. Individual data from 38,274 participants across six cohorts were analyzed for CHD mortality, and 33,394 participants from four cohorts for CHD events.

Among 38,274 adults, 1691 (4.4%) had subclinical hypothyroidism, with 775 (45.8%) of these having positive TPOAbs. Compared with euthyroid individuals, age- and gender-adjusted risks of CHD mortality in subclinical hypothyroidism were similar for those with and without TPOAbs (HR 1.15 vs HR 1.26). Similarly, risks of CHD events did not differ by TPOAb status (HR 1.16 vs HR 1.26). Risks of CHD mortality and events increased with higher thyrotropin levels, but within each thyrotropin stratum, risks did not differ by TPOAb status.

The risk of coronary heart disease associated with subclinical hypothyroidism did not differ based on thyroid peroxidase antibody status. This suggests that biomarkers of thyroid autoimmunity do not provide independent prognostic information for CHD outcomes.


Hair cortisol, perceived stress, and resilience as predictors of coronary arterial disease

Hair cortisol levels show a small, inverse association with coronary artery disease risk, but perceived stress and resilience do not independently predict it.

Can hair cortisol concentration (HCC), perceived chronic stress, and resilience predict the risk of coronary arterial disease (CAD)?

Hypothesis: Hair cortisol concentration (HCC) and perceived chronic stress are associated with CAD risk, and psychological and physiological resilience measures may also play a role.

This was a cross-sectional study of 24 participants. The researchers assessed the risk of CAD associated with HCC and perceived chronic stress (Perceived Stress Score), controlling for age, diabetes, hypertension, dyslipidemia, and obesity. They also evaluated CAD risk with the simultaneous inclusion of psychological and physiological resilience measures (CD-RISC, DHEA-S) in fully adjusted Poisson regression models.

Hair cortisol concentration (HCC) was significantly associated with CAD (incident rate ratio 0.99, confidence interval 0.98-1.00, p = 0.01), but the association was weak and inverse. This association was less pronounced than with dyslipidemia and age. Perceived Stress Score was not significantly associated with CAD. The association between HCC and CAD remained significant after including a combined resiliency score, but resilience itself was not independently significantly associated with CAD.

Hair cortisol concentration (HCC) contributes a small amount to CAD risk in an average-risk population, even after adjusting for multisystem resilience. Perceived stress and resilience measures were not independently significant predictors of CAD in this study.

The study was cross-sectional and involved a small sample size of 24 participants. The magnitude of the association between HCC and CAD was weak and inverse.


ApoB-containing lipoproteins: count, type, size, and risk of coronary artery disease

Total apoB particle count is the primary indicator of atherosclerotic risk, with Lp(a) providing additional independent predictive value, while particle type or size offers little extra insight.

Does the type or size of apoB-containing lipoprotein particles add predictive value for coronary artery disease (CAD) beyond the total apoB concentration?

Hypothesis: The study implicitly hypothesizes that the type or size of apoB particles might offer additional predictive value for CAD beyond the total apoB particle count.

A prospective analysis was conducted on 207,368 UK Biobank participants without prior atherosclerotic disease, diabetes, or active lipid-lowering therapy. Multivariable-adjusted Cox regression models were used to assess the association between incident CAD and nuclear magnetic resonance-measured apoB-P, concentrations of individual lipoprotein classes (VLDL, LDL), size subclasses, average particle diameter, and immunoassay-measured lipoprotein(a) [Lp(a)].

A one standard deviation (SD) increase in apoB-P was associated with a 33% higher CAD risk (HR: 1.33). VLDL particles showed a higher per-particle risk (HR per 100 nmol/L: 1.22) compared to LDL (HR per 100 nmol/L: 1.07), but this difference was balanced when considering relative particle abundance (LDL 91% vs VLDL 9% of total apoB-P), resulting in respective HR per 1-SD of 1.09 for LDL and 1.24 for VLDL. Particle diameter or size subclasses were not associated with CAD after apoB-P adjustment. Lp(a) showed a robust association even after apoB-P adjustment (HR: 1.18) and provided independent prognostic value for CAD (AUC: 0.769 vs 0.774, P < .001).

The total count of apoB-containing lipoprotein particles most accurately reflects lipid-related atherosclerotic risk, and this risk is largely unaffected by the major particle type (VLDL, LDL) or size. An elevated count of Lp(a) adds additional risk, suggesting that assessing atherogenic risk from dyslipidemia is best done by considering both apoB-P and Lp(a) concentrations.


The benefits of measuring the size and number of lipoprotein particles for cardiovascular risk prediction: a meta-analysis

Measuring the number and size of lipoprotein particles provides additional insights into cardiovascular risk beyond traditional cholesterol measurements.

unfavorable-cue: "increased cardiovascular risk" | favorable-cue: "associated with decreased"

What is the cardiovascular risk (CVR) associated with LDL and HDL particle size and number, as measured by nuclear magnetic resonance (NMR) spectroscopy, compared to conventional total cholesterol measurements?

Hypothesis: The study aims to assess the CVR associated with LDL and HDL particle size and number, suggesting these metrics may offer additional insights beyond conventional total cholesterol measurements.

A systematic review and meta-analysis were conducted using MEDLINE and Scopus databases for studies published before January 1, 2019. Included studies were cohort and case-control designs with adult patients, where HDL-P, LDL-P, HDL-Z, and/or LDL-Z were measured by NMR spectroscopy, and cardiovascular events were outcome variables with risk expressed as odds or hazard ratios. A meta-analysis was performed for four LDL and five HDL exposure variables, considering both highest versus lowest quartile and 1-standard deviation increment measures.

The review included 24 studies. An increased number of LDL particles was directly associated with CVR, with a 28% risk increase per standard deviation increment. LDL particle size was inversely associated with CVR, showing an 8% risk reduction per standard deviation increment. The number of small LDL particles increased CVR by 12% per standard deviation increase. Both HDL particle number and size were inversely associated with CVR.

A larger number of LDL particles and smaller LDL particle size are associated with increased cardiovascular risk. Conversely, an increasing number and size of HDL particles are associated with decreased risk. Larger HDL particle size provided greater protection, though this finding was inconsistent across studies.

The abstract does not explicitly state limitations of the study, but it notes that the relationship between larger HDL particle size and greater protection was inconsistent between studies.


Elevated serum uric acid and risk of cardiovascular or all-cause mortality: a meta-analysis

Higher serum uric acid levels are linked to a lower risk of cardiovascular death in hemodialysis patients.

favorable-cue: "associated with a lower"

Does elevated serum uric acid (SUA) increase the risk of cardiovascular or all-cause mortality in maintenance hemodialysis patients?

Hypothesis: The meta-analysis aimed to determine if higher SUA values are a risk factor for cardiovascular or all-cause mortality in maintenance hemodialysis patients, given inconsistent results from previous studies.

A meta-analysis was conducted by searching Pubmed, Embase, and the Cochrane library up to August 31, 2020, for longitudinal studies investigating the association between elevated SUA and cardiovascular or all-cause mortality risk in maintenance hemodialysis patients. Pooled adjusted hazard ratios (HR) and 95% confidence intervals (CI) were calculated using a random-effects model. Ten studies with 264,571 hemodialysis patients were included.

Patients with the highest SUA levels had a decreased risk of cardiovascular mortality (HR = 0.72, 95% CI 0.59-0.87) compared to those with the lowest SUA, after adjusting for confounders. For every 1 mg/dl increase in SUA, the overall risks of all-cause and cardiovascular mortality decreased by 6% (HR = 0.94, 95% CI 0.90-0.99) and 9% (HR = 0.91, 95% CI 0.89-0.94), respectively.

Elevated SUA levels are strongly and independently associated with a lower risk of cardiovascular mortality in maintenance hemodialysis patients.

The study suggests that more designed studies, especially randomized controlled trials, are needed to definitively determine if high SUA levels are an independent risk factor for all-cause mortality in hemodialysis patients.


Impact of Cardiorespiratory Fitness on All-Cause and Disease-Specific Mortality

Biometric Wearables (Sleep, HRV & Recovery)

Higher cardiorespiratory fitness is strongly linked to a lower risk of death from all causes and specific diseases.

What is the impact of cardiorespiratory fitness (CRF) on all-cause and disease-specific mortality?

Hypothesis: The hypothesis is that cardiorespiratory fitness (CRF) is inversely related to all-cause and disease-specific mortality.

This is a review article that synthesizes evidence regarding cardiorespiratory fitness (CRF) and mortality, focusing on advances since 2009. It examines studies that used various methods to assess CRF, including directly measured maximal oxygen uptake (VO2max), estimated exercise tests, and non-exercise prediction equations.

Cardiorespiratory fitness (CRF) has consistently emerged as a strong, independent predictor of all-cause and disease-specific mortality over the past three decades. The inverse relationship between CRF and mortality has been observed despite variations in CRF assessment methods.

Cardiorespiratory fitness (CRF) is a powerful prognostic indicator for all-cause and disease-specific mortality. The American Heart Association advocates for its routine assessment as a clinical vital sign.

The abstract does not explicitly state limitations of the review itself, but it notes that the evidence for CRF's prognostic value exists despite a wide variation of methods used to assess CRF in the studies reviewed.