Food-sourced guanidinoacetic acid and methylation cycle biomarkers in individuals aged one year and older: a population-based cross-sectional study.

PURPOSE: Several preliminary studies suggest dietary guanidinoacetic acid (GAA) might impact methyl group availability and/or methylation biomarkers, fueling ongoing debates. This study aimed to explore the relationship between dietary GAA intake and plasma indicators of the methylation cycle in individuals aged one year and older, using data from the 2001-2002 National Health and Nutrition Examination Survey (NHANES). METHODS: Dietary information was obtained from individuals who completed a 24-hour Dietary Recall, with total daily intake of GAA calculated by aggregating all relevant food items. Relevant variables related to the methylation cycle, such as red blood cell (RBC) folate and serum folate, vitamin B12, total homocysteine (tHCy), and methylmalonic acid (MMA), were identified from the NHANES 2001-2002 laboratory assessments. RESULTS: A total of 9,115 individuals (51.3% females) were included in the final analysis. Linear regression unveiled a significant association between higher GAA intake and diminished RBC folate (p < 0.001), serum folate (p < 0.001), and MMA levels (p = 0.007). It also revealed an elevation in tHCy levels with increased GAA intake (p < 0.001). These associations remained significant even after adjusting for demographic variables and dietary factors pertinent to the methylation cycle (p < 0.05). CONCLUSION: Our findings suggest that dietary exposure to GAA (resulting in conversion to creatine) could be considered a nutritional factor associated with the consumption of methyl groups in the general population.

Post-marketing surveilance study of creatine-guanidinoacetic acid safety in healthy adults.

A post-marketing surveillance study assessed the adverse events and possible risk of elevated homocysteine levels after the supplementation with creatine-guanidinoacetic acid mixture in apparently healthy adults. The participants were recruited through social media platforms and online discussion boards, with side effects and total plasma homocysteine (T-Hcy) levels evaluated regularly during a supplementation period of 6 months. Thirthy eight individuals (n = 38, 34.2% female) completed the evaluation period and were included in the final analyses. Serious side effects were absent. Two participants (5.3%) reported transitional nausea during the introductory weeks of the supplementation; no participants stopped the treatment. Baseline T-Hcy levels were 11.6 ± 3.1 µmol/L (95% confidence interval [CI], from 10.6 to 12.6). The intervention induced a mild reduction in T-Hcy levels across the monitoring period (p = 0.028), with T-Hcy levels after 1, 2, 3, and 6 months were 10.4 ± 3.0 µmol/L, 10.6 ± 2.9 µmol/L, 10.1 ± 2.7 µmol/L, and 9.3 ± 2.8 µmol/L, respectively. These findings suggest the overall tolerability of creatine-guanidinoacetic mixture in healthy adults, with homocysteine-increasing risk of no concern.

Molecular Hydrogen for Outpatients with COVID-19 (Hydro-COVID): A Phase 3 Randomised, Triple-Blinded, Pragmatic, Placebo-Controlled, Multicentre Trial.

Background. Due to its antioxidant, anti-inflammatory, anti-apoptosis, and anti-fatigue properties, molecular hydrogen (H2) is potentially a novel therapeutic nutrient for patients with coronavirus acute disease 2019 (COVID-19). We determined the efficacy and safety profile of hydrogen-rich water (HRW) to reduce the risk of COVID-19 progression. Methods: We also conducted a phase 3, triple-blind, randomised, placebo-controlled trial to evaluate treatment with HRW initiated within 5 days after the onset of signs or symptoms in primary care patients with mild-to-moderate, laboratory-confirmed COVID-19. Participants were randomised to receive HRW or placebo twice daily for 21 days. The incidence of clinical worsening and adverse events were the primary endpoints. Results: A total of 675 participants were followed up to day 30. HRW was not superior to placebo in preventing clinical worsening at day 14: in H2 group, 46.1% in the H2 group, 43.5% in the placebo group, hazard ratio 1.09, 90% confidence interval [0.90-1.31]. One death was reported at day 30 in the H2 group and two in the placebo group at day 30. Adverse events were reported in 91 (27%) and 89 (26.2%) participants, respectively. Conclusions: HRW taken twice daily from the onset of COVID-19 symptoms for 21 days did not reduce clinical worsening.

Associations between levels of physical activity and satisfaction with life among Norwegian adolescents: a cross-sectional study.

Background: A robust association between physical activity (PA) and satisfaction with life (SWL) has been established, wherein self-efficacy has been identified as a mediator across different populations. However, there is a need to further examine the relationship between PA and SWL and whether self-efficacy act a as mediator within different levels of PA among Norwegian adolescents. Thus, the objective of this study was to explore the relationship between levels of PA and SWL by testing for self-efficacy as a possible mediator. Methods: Cross-sectional data from the 2022 Norwegian Ungdata Survey was utilized. Data included demographics and various health data that was collected anonymously. The electronic survey took place in classrooms and was administered by the respective teacher. Permission to access and use data was approved by the Norwegian Agency for Shared Services in Education and Research (SIKT). Statistical analyses were conducted using the PROCESS macro by Andrew Hayes for SPSS software. Results: Descriptive findings revealed that girls reported lower self-efficacy than boys (14.2 vs. 15.5, with a maximum of 20) and lower SWL (6.8 vs. 7.6, with a maximum of 10). About one out of five girls and one out of seven boys reported no days of weekly PA, whereas 4% of girls and 9.5% of boys adhered to the PA-recommendation of 60-min of daily exercise. Associations between PA levels and SWL was mediated by self-efficacy (all p < 0.05), with the highest indirect effect (56.3%) revealed in the association between those adhering to the PA-recommendations and SWL. Conclusions: Norwegian girls reported more sedentary behavior, less PA, lower self-efficacy, and lower SWL than boys across all grade levels. Mediation analysis revealed that up to 56.3% of the enhancement in SWL among those adhering to 60-min of PA recommendations was explained by increased self-efficacy. Norwegian government and policymakers should promote initiatives and regulations focusing on higher levels of PA to foster a resilient adolescent population with higher individual beliefs and higher subjective wellbeing.

Decreased Cerebral Creatine and N-Acetyl Aspartate Concentrations after Severe COVID-19 Infection: A Magnetic Resonance Spectroscopy Study.

Background/Objectives: The aim of this study was to evaluate brain metabolism using MR spectroscopy (MRS) after recovery from Coronavirus disease (COVID-19) and to test the impact of disease severity on brain metabolites. Methods: We performed MRS on 81 individuals (45 males, 36 females, aged 40-60), who had normal MRI findings and had recovered from COVID-19, classifying them into mild (17), moderate (36), and severe (28) groups based on disease severity during the acute phase. The study employed two-dimensional spectroscopic imaging above the corpus callosum, focusing on choline (Cho), creatine (Cr), and N-acetylaspartate (NAA). We analyzed Cho/Cr and NAA/Cr ratios as well as absolute concentrations using water as an internal reference. Results: Results indicated that the Cho/Cr ratio was higher with increasing disease severity, while absolute Cho and NAA/Cr ratios showed no significant differences across the groups. Notably, absolute Cr and NAA levels were significantly lower in patients with severe disease. Conclusions: These findings suggest that the severity of COVID-19 during the acute phase is associated with significant changes in brain metabolism, marked by an increase in Cho/Cr ratios and a reduction in Cr and NAA levels, reflecting substantial metabolic alterations post-recovery.

Hydrogen as an innovative nootropic in health and disease.

Molecular hydrogen (H2, dihydrogen) is an antioxidant and signaling molecule with potent antioxidative, antiapoptotic, and anti-inflammatory properties. Despite the growing interest in H2 as a potential therapeutic agent, the evidence regarding its potential as a nootropic remains limited. Only a handful of studies on the human population have evaluated its effects, although there are suggestive indications of its efficacy. The present paper overviews H2's potential as a novel agent for improving cognitive functions in health and disease contexts, highlighting its mechanisms of action and areas for further investigation. Current evidence suggests that H2 improves executive function, alertness and memory in several clinical trials, from healthy young and elderly individuals to individuals with altered circadian rhythms, neurodegenerative disorders, and cancer. Further investigations are needed to confirm the potential positive effects of dihydrogen as a nootropic agent in both health and disease.

Association between dietary intake of creatine and female reproductive health: Evidence from NHANES 2017-2020.

The hormonal changes in women influence creatine dynamics, emphasizing its potential importance during menstruation, pregnancy, postpartum, menopause, and postmenopause. Yet, limited research explores creatine's impact on female reproductive health at the population level. Our study investigated the relationship between dietary creatine intake and reproductive health indices in US women using data from the 2017-2020 National Health and Nutrition Examination Survey (NHANES). We extracted a dataset containing females aged 12 years and above who provided details about their reproductive health and dietary habits. Daily creatine intake was quantified as a relative amount (mg per kg body mass) and did not include creatine from dietary supplements and pharmacological agents. A daily requirement for dietary creatine for healthy women was employed to classify respondents into two separate subpopulations: (1) suboptimal intake of creatine (<13 mg per kg body mass per day) or (2) recommended intake (dietary creatine ≥ 13 mg per kg body mass per day). A total of 4522 female participants from the NHANES study (age 44.5 ± 20.5 years) provided data on their reproductive health and dietary intake. The average daily creatine intake for the group was 10.5 ± 10.8 mg per kg body mass. The odds ratio for having irregular periods in women consuming ≥13 mg of creatine per kg body mass daily (recommended intake) compared to those with suboptimal intake was 0.75 (95% CI, from 0.66 to 0.86), indicating a significant association between higher intake of dietary creatine and lower risk of oligomenorrhea (p < .001). Moreover, women consuming less than 13 mg of creatine per kg body mass faced an increased risk of fetal macrosomia (OR 1.26; p = .04), pelvic infection (OR 1.68; p = .01), hysterectomy (OR 1.42; p < .001), oophorectomy (OR 1.54; p < .001), and receiving hormone replacement therapy (OR 1.26; p = .02). Consuming a creatine-rich diet has been linked to lower risks of reproductive issues in US women aged 12 and above. Those consuming ≥13 mg of creatine per kg body mass daily showed notably lower risks of irregular menstrual periods, obstetric conditions, and pelvic pathology. Further studies are needed to confirm these potential benefits.

The impact of six-week dihydrogen-pyrroloquinoline quinone supplementation on mitochondrial biomarkers, brain metabolism, and cognition in elderly individuals with mild cognitive impairment: a randomized controlled trial.

OBJECTIVES: To assess the impact of medium-term supplementation with dihydrogen and pyrroloquinoline quinone (PQQ) on mitochondrial biomarkers, brain metabolism, and cognition in elderly individuals diagnosed with mild cognitive impairment. DESIGN: A parallel-group, randomized, placebo-controlled, double-blind experimental design, maintaining a 1:1 allocation ratio between the experimental group (receiving the dihydrogen-producing minerals and PQQ) and the control group (receiving the placebo) throughout the trial. SETTING AND PARTICIPANTS: Thirty-four elderly individuals with mild cognitive impairment (mean age 71.9 ± 3.8 years; 28 females) voluntarily provided written consent to participate in this trial. Participants were assigned in a double-blind parallel-group design to receive either a dihydrogen-PQQ mixture (Alpha Hope®, CalerieLife, Irvine, CA) or placebo twice daily for a 6-week intervention period. METHODS: The primary endpoint was the change in serum brain-derived neurotrophic factor (BDNF) from baseline to the 6-week follow-up; secondary outcomes included cognitive function indices, specific metabolites in brain tissue, brain oxygenation, and the prevalence and severity of side effects. Interaction effects (time vs. intervention) were evaluated using two-way ANOVA with repeated measures and Friedman's 2-way ANOVA by ranks, for normally distributed data with homogeneous variances and non-homogeneous variances, respectively. RESULTS: Dihydrogen-PQQ resulted in a significant elevation in serum BDNF levels at the six-week follow-up (P = 0.01); conversely, no changes in BDNF levels were observed in the placebo group throughout the study duration (P = 0.27). A non-significant trend in the impact of interventions on BDNF levels was observed (treatment vs. time interaction, P = 0.14), suggesting a tendency for dihydrogen-PQQ to upregulate BDNF levels compared to the placebo. A significant interaction effect was observed for the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) scores in the orientation domain (P = 0.03), indicating the superiority of dihydrogen-PQQ over placebo in enhancing this cognitive aspect. Cerebral oxygenation saturation exhibited a significant increase following the administration of the dihydrogen-PQQ mixture, from 48.4 ± 7.2% at baseline to 52.8 ± 6.6% at 6-week post-administration (P = 0.005). In addition, brain N-acetyl aspartate levels significantly increased at seven out of thirteen locations post-intervention in participants receiving the mixture (P ≤ 0.05). CONCLUSIONS: Despite the limited number of participants included in the study for interpreting clinical parameters, the dihydrogen-PQQ mixture blend shows promise as a potential dietary intervention for enhancing mental orientation and brain metabolism in individuals with age-related mild cognitive decline.

Dietary creatine is associated with lower serum neurofilament light chain levels.

Low creatine availability may be linked to an elevated risk of neuronal damage, yet this association remains inadequately explored at the population level. Utilizing 2013-2014 National Health and Nutrition Examination Survey data, the current study found a negative correlation between dietary creatine intake and serum levels of neurofilament light chain (NfL; a biomarker for neuronal damage) in a cohort of 1912 individuals (52.2% females) aged 20-75 years. This inverse association persisted even after adjusting for other nutritional variables known to influence neuronal viability. The observed pattern, where increased dietary creatine intake was associated with reduced circulating NfL levels, suggests potential protective effects of creatine against neuronal injury.

Adherence to sleep recommendations is associated with higher satisfaction with life among Norwegian adolescents.

BACKGROUND: Sleep plays a crucial role in the health and well-being of adolescents; however, inadequate sleep is frequently reported in numerous countries. This current paper aimed to describe sleep duration, factors impacting sleep, consequences of insufficient sleep and satisfaction with life in Norwegian adolescents, stratified by sex and by adherence to the 8-hour sleep recommendation, and to examine potential associations between adherence to the 8-hours sleep recommendation and satisfaction with life. METHODS: This is a cross-sectional study using data from the Norwegian Ungdata Survey, collected in 2021. Adolescents from five Norwegian counties were included, comprising a total of 32,161 upper secondary school students. Study variables were collected through an electronic questionnaire administered during school hours and all data are anonymous. Descriptive data of sleep patterns are presented, and linear regressions were conducted adjusting for SES, perceived stress, physical activity level, over-the-counter analgesics use, grade level and screen time. RESULTS: 73% of adolescents did not adhere to the 8-hours of sleep recommendation per night, with similar results for girls and boys. 64% reported tiredness at school (minimum 1-2 days weekly) and 62% reported that screen time negatively affected their ability to sleep. 23% reported that gaming affected their sleep, with a higher prevalence in boys than girls. Satisfaction with life score was 7.0 ± 1.9 points (out of 10) for the total sample, with higher scores for boys (7.3 ± 1.8 points) than girls (6.9 ± 1.9 points). Regressions revealed a positive association with satisfaction with life (B = 0.31, 95% [0.15 to 0.48]) in adolescents adhering to sleep recommendation of 8h compared to the ones not adhering to the sleep recommendation. CONCLUSIONS: Most Norwegian adolescents fail to adhere to the 8-hours of sleep recommendation and the majority feel tired at school or during activities. More than half of adolescents reported that screen time negatively affected their ability to sleep. Adhering to the sleep recommendation was associated with higher life satisfaction. Our findings highlight the importance of sufficient sleep in adolescents, while future research is needed to examine other sleep related measures on adolescents´ satisfaction with life.

Eight-Week Creatine-Glucose Supplementation Alleviates Clinical Features of Long COVID.

Preliminary studies demonstrated beneficial effects of dietary creatine across different post-viral fatigue syndromes. Creatine is often co-administered with glucose to improve its potency yet whether glucose boost the efficacy of creatine in long COVID remains currently unknown. In this report, we investigate the effects of 8-wk creatine intake with and without glucose on patient-reported outcomes, exercise tolerance, and tissue creatine levels in patients with long COVID. Fifteen male and female long COVID adult patients (age 39.7±16.0 y; 9 women) with moderate fatigue and at least one of additional long COVID-related symptoms volunteered to participate in this randomized controlled parallel-group interventional trial. All patients were allocated in a double-blind parallel-group design (1 : 1 : 1) to receive creatine (8 g of creatine monohydrate per day), a mixture of creatine and glucose (8 g of creatine monohydrate and 3 g of glucose per day), or placebo (3 g of glucose per day) t.i.d. during an 8-wk intervention interval. Two-way ANOVA with repeated measures (treatment vs. time interaction) revealed significant differences in changes in total creatine levels between the groups, showing an interaction effect at two brain locations (right precentral white matter F=34.740, p=0.008; partial η2=0.72; left paracentral grey matter F=19.243, p=0.019; partial η2=0.88), with creatine and creatine-glucose outcompeted placebo to elevate creatine levels at these two locations. Several long COVID symptoms (including body aches, breathing problems, difficulties concentrating, headache, and general malaise) were significantly reduced in creatine-glucose group at 8-wk follow-up (p≤0.05); the effect sizes for reducing body aches, difficulties concentrating, and headache were 1.33, 0.80, and 1.12, respectively, suggesting a large effect of creatine-glucose mixture for these outcomes. Our preliminary findings suggest that supplying exogenous creatine with glucose could be recommended as an effective procedure in replenishing brain creatine pool and alleviating long COVID features in this prevalent condition.

Community-based interventions targeting multiple forms of malnutrition among adolescents in low-income and middle-income countries: protocol for a scoping review.

BACKGROUND: Adolescent malnutrition is a significant public health challenge in low-income and middle-income countries (LMICs), with long-term consequences for health and development. Community-based interventions have the potential to address multiple forms of malnutrition and improve the health outcomes of adolescents. However, there is a limited understanding of the content, implementation and effectiveness of these interventions. This scoping review aims to synthesise evidence on community-based interventions targeting multiple forms of malnutrition among adolescents in LMICs and describe their effects on nutrition and health. METHODS AND ANALYSIS: A comprehensive search strategy will be implemented in multiple databases including MEDLINE (through PubMed), Embase, CENTRAL (through Cochrane Library) and grey literature, covering the period from 1 January 2000 to 14 July 2023. We will follow the Participants, Concept and Context model to design the search strategy. The inclusion criteria encompass randomised controlled trials and quasi-experimental studies focusing on adolescents aged 10-19 years. Various types of interventions, such as micronutrient supplementation, nutrition education, feeding interventions, physical activity and community environment interventions, will be considered. Two reviewers will perform data extraction independently, and, where relevant, risk of bias assessment will be conducted using standard Cochrane risk-of-bias tools. We will follow the PRISMA Extension for Scoping Reviews checklist while reporting results. ETHICS AND DISSEMINATION: The scope of this scoping review is restricted to publicly accessible databases that do not require prior ethical approval for access. The findings of this review will be shared through publications in peer-reviewed journals, and presentations at international and regional conferences and stakeholder meetings in LMICs. SCOPING REVIEW REGISTRATION: The final protocol was registered prospectively with the Open Science Framework on 19 July 2023 (https://osf.io/t2d78).

Effects of HMB on Endurance Performance in a Healthy Population: A Systematic Review and Meta-Analysis.

ABSTRACT: Fernández-Landa, J, Todorovic, N, Santibañez-Gutierrez, A, Ostojic, SM, Calleja-González, J, Sekulic, D, and Mielgo-Ayuso, J. Effects of HMB on endurance performance in a healthy population: a systematic review and meta-analysis. J Strength Cond Res 38(4): e202-e210, 2024-ß-hydroxy-ß-methylbutyrate (HMB) has been used extensively as a dietary supplement for athletes and physically active people. However, the ergogenic effect of HMB supplementation on endurance performance is still unclear. Therefore, this systematic review and meta-analysis (SRMA) aimed to assess HMB supplementation on endurance performance and V̇O 2 max . This SRMA followed PRISMA guidelines. Three electronic databases were searched (PubMed/Medline, Web of Science [WOS], and Scopus) from inception until April 3, 2023. In this SRMA, human experimental trials, controlled with a placebo group, assessing the effect of HMB supplementation on endurance performance in a healthy population were included. The quality of the studies was assessed by the Physiotherapy Evidence Database (PEDro) scale. The study protocol was registered in the Prospective Register of Systematic Review (PROSPERO): CRD42022341790. Eleven studies involving 279 participants met the inclusion criteria. The results displayed a significant improvement on endurance performance (pooled standardized mean difference [SMD] = 0.58 [0.28-0.87]) and V̇O 2 max (pooled SMD = 0.58 [0.21-0.95]) after HMB ingestion. Moreover, after the exclusion of the studies not evenly distributed around the base of the funnel plot, the results continued to be significantly positive in endurance performance (pooled SMD = 0.38 [0.22-0.53]) and V̇O 2 max (pooled SMD = 0.25 [0.09-0.42]). In conclusion, HMB (3 g·d -1 ) ingestion during 2-12 weeks significantly improves endurance performance and V̇O 2 max .

Molecular nutrition in life course perspective: Pinpointing metabolic pathways to target during periconception.

Lifecourse nutrition encompasses nourishment from early development into parenthood. From preconception and pregnancy to childhood, late adolescence, and reproductive years, life course nutrition explores links between dietary exposures and health outcomes in current and future generations from a public health perspective, usually addressing lifestyle behaviours, reproductive well-being and maternal-child health strategies. However, nutritional factors that play a role in conceiving and sustaining new life might also require a molecular perspective and recognition of critical interactions between specific nutrients and relevant biochemical pathways. The present perspective summarises evidence about the links between diet during periconception and next-generation health and outlines the main metabolic networks involved in nutritional biology of this sensitive time frame.

Nutrition in a lifecourse perspective: From molecular aspects to public health approaches.

This Special Issue covers a variety of topics related to nutrition from a lifecourse perspective, addressing diet in sensitive periods (preconception, pregnancy and infancy/toddlerhood), in different contexts, spanning from molecular nutrition to settings and gatekeepers of diet in these sensitive periods. It highlights challenges and research gaps within the field.

Effects of six-month creatine supplementation on patient- and clinician-reported outcomes, and tissue creatine levels in patients with post-COVID-19 fatigue syndrome.

Dietary creatine has been recently put forward as a possible intervention strategy to reduce post-COVID-19 fatigue syndrome yet no clinical study so far evaluated its efficacy and safety for this perplexing condition. In this parallel-group, randomized placebo-controlled double-blind trial, we analyzed the effects of 6-month creatine supplementation (4 g of creatine monohydrate per day) on various patient- and clinician-reported outcomes, and tissue creatine levels in 12 patients with post-COVID-19 fatigue syndrome. Creatine intake induced a significant increase in tissue creatine levels in vastus medialis muscle and right parietal white matter compared to the baseline values at both 3-month and 6-month follow-ups (p < .05). Two-way analysis of variance with repeated measures revealed a significant difference (treatment vs. time interaction) between interventions in tissue creatine levels (p < .05), with the creatine group was superior to placebo to augment creatine levels at vastus medialis muscle, left frontal white matter, and right parietal white matter. Creatine supplementation induced a significant reduction in general fatigue after 3 months of intake compared to baseline values (p = .04), and significantly improved scores for several post-COVID-19 fatigue syndrome-related symptoms (e.g., ageusia, breathing difficulties, body aches, headache, and difficulties concentrating) at 6-month follow-up (p < .05). Taking creatine for 6 months appears to improve tissue bioenergetics and attenuate clinical features of post-COVID-19 fatigue syndrome; additional studies are warranted to confirm our findings in various post-COVID-19 cohorts.

Resistance Exercise and Creatine Supplementation on Fat Mass in Adults < 50 Years of Age: A Systematic Review and Meta-Analysis.

The combination of resistance exercise and creatine supplementation has been shown to decrease body fat percentage in adults ≥ 50 years of age. However, the effect on adults < 50 years of age is currently unknown. To address this limitation, we systematically reviewed the literature and performed several meta-analyses comparing studies that included resistance exercise and creatine supplementation to resistance exercise and placebo on fat mass and body fat percentage Twelve studies were included, involving 266 participants. Adults (<50 years of age) who supplemented with creatine and performed resistance exercise experienced a very small, yet significant reduction in body fat percentage (-1.19%, p = 0.006); however, no difference was found in absolute fat mass (-0.18 kg, p = 0.76). Collectively, in adults < 50 years of age, the combination of resistance exercise and creatine supplementation produces a very small reduction in body fat percentage without a corresponding decrease in absolute fat mass.