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 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 XX(X): 000-000, 2023-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 V̇O2 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 V̇O2 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 V̇O2 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 V̇O2 max.

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.

"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.

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.

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.

Effects of Creatine Monohydrate on Endurance Performance in a Trained Population: A Systematic Review and Meta-analysis.

BACKGROUND: There is robust evidence that creatine monohydrate supplementation can enhance short-term high-intensity exercise in athletes. However, the effect of creatine monohydrate supplementation on aerobic performance and its role during aerobic activities is still controversial. OBJECTIVE: The purpose of this systematic review and meta-analysis was to evaluate the supplementation effects of creatine monohydrate on endurance performance in a trained population. METHODS: The search strategy in this systematic review and meta-analysis was designed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and PubMed/MEDLINE, Web of Science, and Scopus databases were explored from inception until 19 May, 2022. Only human experimental trials, controlled with a placebo group, evaluating the effects of creatine monohydrate supplementation on endurance performance in a trained population were analyzed in this systematic review and meta-analysis. The methodological quality of included studies was evaluated using the Physiotherapy Evidence Database (PEDro) scale. RESULTS: A total of 13 studies satisfied all the eligibility criteria and were included in this systematic review and meta-analysis. The results for the pooled meta-analysis showed a non-significant change in endurance performance after creatine monohydrate supplementation in a trained population (p = 0.47), with a trivial negative effect (pooled standardized mean difference = - 0.07 [95% confidence interval - 0.32 to 0.18]; I2 = 34.75%). Further, after excluding the studies not evenly distributed around the base of the funnel plot, the results were similar (pooled standardized mean difference = - 0.07 [95% confidence interval - 0.27 to 0.13]; I2 = 0%; p = 0.49). CONCLUSIONS: Creatine monohydrate supplementation was shown to be ineffective on endurance performance in a trained population. CLINICAL TRIAL REGISTRATION: The study protocol was registered in the Prospective Register of Systematic Review (PROSPERO) with the following registration number: CRD42022327368.

Creatine consumption and liver disease manifestations in individuals aged 12 years and over.

Despite the overwhelming safety evidence concerning creatine intake in various settings, there is still incomplete information whether dietary creatine affects liver health at the population level. The main aim of this cross-sectional population-based study was to evaluate the association between creatine intake through regular diet and liver disease manifestations, including liver fibrosis and hepatic steatosis, among individuals aged 12 years and over, using open-source data from the 2017-2018 U.S. National Health and Nutrition Examination Survey (NHANES). A total of 9254 male and female participants of all ages were included in the 2017-2018 NHANES round. We extracted data from the total sample population for participants who provided dietary data for individual foods via dietary interviews and examination data from liver ultrasound transient elastography. The final study sample consisted of 5957 participants (mean age 44.7 ± 21.0 years; 50.1% women), and the mean dietary creatine intake across the study population was 0.88 ± 0.71 g/day. Liver fibrosis and cirrhosis were diagnosed in 1703 (28.7%) and 288 (4.8%) participants, respectively; hepatic steatosis was identified in 2595 (43.7%) individuals. Binary logistic regression with multivariable model adjusted for age, gender, family income to poverty ratio, body mass index, total energy intake, and alcohol consumption showed that consuming more creatine (≥2 g/day) did not significantly increase the risk of liver fibrosis (OR = 0.92, 95% CI 0.70-1.21, p = .57), cirrhosis (OR = 0.94, 95% CI 0.53-1.65, p = .82), or hepatic steatosis (OR = 0.77, 95% CI 0.59-1.02, p = .07), as compared to participants who ingested <1 g of creatine daily. Dietary exposure to creatine through a regular diet is not associated with an increase in disease manifestations in individuals 12 years and over; further research is warranted to address the effects of excessive creatine intake (≥5 g/day) through a regular diet on liver health at the population level.

Medium-chain triglycerides may improve memory in non-demented older adults: a systematic review of randomized controlled trials.

BACKGROUND: Ketosis has been exploited for its neuroprotective impact and treatment of neurological conditions via ketone production. Exogenous medium-chain triglyceride (MCT) supplementation may induce nutritional ketosis. The aim of this systematic review is to explore the effects of MCTs on memory function in older adults without cognitive impairment. METHODS: A systematic literature search of PubMed, Cochrane Library, Scopus, and Web of Science was employed from inception until April 2022 for randomized controlled trials (RCTs) in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, investigating the impact of MCT oils on components of memory. Risk of bias (RoB2) tool was utilized for quality assessment. RESULTS: Six trials were included for qualitative synthesis, in which two studies examined the effect of MCTs through a ketogenic meal. MCT supplementation compared to controls was associated with improved indices of memory function in 4 out of 6 studies, particularly working memory. A meta-analysis was not employed due to the low number of studies, therefore, a true effect measure of MCT supplementation was not explored. CONCLUSIONS: MCT supplementation may enhance working memory in non-demented older adults. These effects may be more prominent in individuals with lower baseline scores, from short and long-term supplementation. Further studies are warranted to confirm these findings in terms of optimal dose and MCTs composition, which may protect from memory decline during aging.

Malproduction of endogenous hydrogen gas in COVID-19.

The molecular footprints of COVID-19 occur everywhere, even reaching the family of biologically active gases and gasotransmitters. Besides nitric oxide and hydrogen sulfide, COVID-19 might also alter the homeostasis of dihydrogen (H2), another gaseous bioactive molecule produced endogenously by the human gut bacteria. Many studies have shown various alterations of the gut microbiota in patients with coronavirus disease 2019, including the lower abundance of hydrogen-producing bacteria that could instigate the shortage of hydrogen output. Since dihydrogen has many important bioactivities, including cytoprotective, antioxidant, anti-inflammatory, and antiapoptotic, its malproduction in COVID-19 might contribute to the disease progression and severity. On the other hand, replenishing dihydrogen by exogenous administration could be beneficial in COVID-19 for both patient- and clinical-reported outcomes. Assessing low dihydrogen along with H2 supplementation to restore normal levels could be thus combined via theranostic approaches to aid COVID-19 diagnosis and treatment.