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).

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.

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 .

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.

Molecular hydrogen modulates brain glutamate/GABA-glutamine cycle in overweight humans.

Introduction: We evaluated whether 12-week intake of molecular hydrogen (H2) in 5 overweight adults (3 women; age: 50.2 ±11.9 years, body mass index: 29.4 ±2.1 kg/m2) affects brain levels of the glutamate-glutamine-GABA cycle, critical amino acid neurotransmitters in the mechanism of neuronal activation during appetite regulation. Methods: A 1.5-T single-voxel proton magnetic resonance spectroscopy was used to assess the tissue concentrations of relevant metabolites. Results: The mean glutamate and glutamate-plus-glutamine levels at the posterior cingulate gyrus decreased significantly during the study; this was accompanied by a significant drop in GABA levels at left prefrontal white matter, and glutathione levels at anterior cingulate gyrus. No changes in the brain metabolites were found in the comparable group of overweight individuals (n = 4, 2 women; age: 41.0 ±13.9, BMI 26.8 ±1.3 kg/m2) followed-up in the past without this treatment. Conclusions: We showed a possible hydrogen-driven upregulation of neurotransmitters involved in appetite stimulation leading to hunger suppression and weight loss. Further studies analyzing appetite-controlling metabolic pathways affected by H2 would require monitoring of additional biomarkers of satiation and satiety during different feeding regimens.

Individual nutrients and serum klotho levels in adults aged 40-79 years.

Several dietary factors (including adherence to the Mediterranean diet or higher nut intake) seem to positively affect circulating antiaging Klotho protein levels; yet, a description of possible relationships between individual nutrients and Klotho activity has not been evaluated. We analyzed the association of dietary intake of individual macro- and micronutrients and nonnutritive food components with circulating Klotho levels in a sample of 40- to 79-year-old US adults. Data from the 2015-2016 National Health and Nutrition Examination Survey were analyzed. Nutrient/food component intakes were calculated in relation to total energy intake using the nutrient density method, and available pristine serum samples were analyzed for serum Klotho concentrations. The final study sample consisted of 2637 participants (mean age 59.0 ± 10.7 years; 52% women). Higher Klotho concentrations were found with higher intake of carbohydrates (p < .001), total sugars (p < .001), dietary fibers (p < .001), vitamin D (p = .05), total folates (p = .015), and copper (p = .018). The results of the regression analysis with a crude model showed significant associations among five nutrients/food components (carbohydrates, alcohol, total sugars, dietary fibers, and niacin) and soluble Klotho levels across the sample. After adjusting the models for age and gender, the nutrient/food component-Klotho association remained significant for carbohydrates, total sugars, and alcohol (p < .05). Dietary exposure to individual nutrients and nonnutritive food components appears to be associated with Klotho activity; however, additional research is needed to investigate the relationship between cause and effect in diet composition-Klotho interplay.

The Effects of Hydrogen-Rich Water on Blood Lipid Profiles in Clinical Populations: A Systematic Review and Meta-Analysis.

Over the last two decades, a plethora of disease models and human studies have confirmed the beneficial effects of molecular hydrogen (H2), a simple biotherapeutic gas. Recent small-scale studies evaluating the effects of hydrogen-rich water (HRW) on various metabolic conditions pointed to advantageous effects of HRW in regulating blood lipid profiles. However, to the best of the authors' knowledge, no systematic review and/or meta-analysis (SRMA) were published considering HRW consumption and lipid/lipoprotein status. Therefore, the aim of this SRMA was to assess the effects of HRW consumption on blood lipid panel in clinical populations. The search strategy was designed using PRISMA guidelines, and the databases PubMed/Medline, Web of Science, and Scopus were explored from inception until 4 October 2022. A total of seven studies satisfied all the eligibility criteria and were included in SRMA. The results for the pooled meta-analysis showed a significant reduction in total cholesterol, low-density lipoprotein, and triglycerides after HRW intake (p = 0.01), with small to moderate effects (pooled SMD = -0.23 (from -0.40 to 0.05); pooled SMD = -0.22 (from -0.39 to 0.04); pooled SMD = -0.38 (from -0.59 to 0.18), respectively). Our findings indicate that drinking HRW can significantly improve lipid status in the clinical populations. Additional studies are warranted to further validate this connection.

"Heads Up" for Creatine Supplementation and its Potential Applications for Brain Health and Function.

There is emerging interest regarding the potential beneficial effects of creatine supplementation on indices of brain health and function. Creatine supplementation can increase brain creatine stores, which may help explain some of the positive effects on measures of cognition and memory, especially in aging adults or during times of metabolic stress (i.e., sleep deprivation). Furthermore, creatine has shown promise for improving health outcome measures associated with muscular dystrophy, traumatic brain injury (including concussions in children), depression, and anxiety. However, whether any sex- or age-related differences exist in regard to creatine and indices of brain health and function is relatively unknown. The purpose of this narrative review is to: (1) provide an up-to-date summary and discussion of the current body of research focusing on creatine and indices of brain health and function and (2) discuss possible sex- and age-related differences in response to creatine supplementation on brain bioenergetics, measures of brain health and function, and neurological diseases.

Guanidinoacetic acid in human nutrition: Beyond creatine synthesis.

Guanidinoacetic acid (GAA) is a nutrient that has been used in human nutrition since the early 1950s. Recommended for its role in creatine biosynthesis, GAA demonstrated beneficial energy-boosting effects in various clinical conditions. Dietary GAA has also been suggested to trigger several creatine-independent mechanisms. Besides acting as a direct precursor of high-energy phosphagen creatine, dietary GAA is suggested to reduce blood glucose concentration by acting as an insulinotropic food compound, spare amino acid arginine for other metabolic purposes (including protein synthesis), modulate taste, and perhaps alter methylation and fat deposition in various organs including the liver. GAA as a food component can have several important metabolic roles beyond creatine biosynthesis; future studies are highly warranted to address GAA overall role in human nutrition.

Cataloguing guanidinoacetic acid content in nutritional supplements.

Guanidinoacetic acid (GAA, also known as glycocyamine or guanidinoacetate) is a naturally occurring alpha amino acid derivative and newly recognized dietary compound obtainable by different foods and nutritional supplements. Anecdotal evidence suggests that the GAA exposure from supplements might be a major source of GAA supply, out-competing other food sources for several orders of magnitude. This original technical paper summarizes information about GAA levels in different nutritional supplements, as derived from the U.S. National Institutes of Health dietary supplement database.