Search Results (45)

Background/Objectives Sports-related musculoskeletal injuries remain a major challenge in physically active populations, with substantial interindividual variability in susceptibility and recovery that cannot be fully explained by biomechanics or genetics alone. Epigenetic mechanisms, including DNA methylation, histone modifications, and non-coding RNAs, provide a dynamic interface through which mechanical loading, inflammation, and metabolic signals regulate gene expression during tissue adaptation and repair. This narrative review synthesizes current evidence on “epigenetically active” dietary supplements and their potential relevance to sports injuries, focusing on methyl donors, polyphenols, omega-3 fatty acids, vitamin D, and redox-active nutrients. Methods Targeted searches of PubMed, Scopus, and Web of Science (2000–2026) were performed using epigenetics-, injury-, exercise-, and supplementation-related terms, prioritizing mechanistic and translational evidence. Results Available data indicate that these compounds can influence molecular mechanisms implicated in musculoskeletal recovery. However, human evidence is largely derived from peripheral tissues and indirect molecular markers, with limited clear linkage to clinically significant injury outcomes such as injury incidence, severity, or return-to-play timelines. Accordingly, these nutrients are best viewed as modulators of recovery-related biology rather than as direct therapeutic agents. Conclusions This review highlights a notable translational gap between mechanistic plausibility and clinical evidence and discusses practical implications for sports nutrition from a personalized perspective. Future research priorities include tissue-relevant epigenetic assessments, integration of multi-omics approaches, and longitudinal trials incorporating injury endpoints. Nutritional epigenomics, therefore, represents a promising avenue to support musculoskeletal health while underscoring the need for rigorous clinical validation. Full article

Methyl-donor nutrients, including folate, vitamin B12, vitamin B6, choline, betaine, and methionine, play indispensable roles in one-carbon metabolism and govern key processes such as DNA methylation, nucleotide synthesis, and genomic maintenance. Yet despite decades of research, their relationship with cancer remains paradoxical and frequently misunderstood. Much of the confusion arises from an overreliance on epidemiological studies that use cancer incidence as a late-stage endpoint, thereby obscuring how the biological actions of methyl donors differ fundamentally across the continuum from precancerous lesions to established tumors. By synthesizing evidence from mechanistic studies, precancerous lesion research, and early-stage carcinogenic models, this review suggests that adequate methyl-donor availability may be protective during the earliest phases of cancer development. However, these same nutrients may later become substrates hijacked by neoplastic cells to fuel rapid proliferation, maintain oncogenic methylation programs, and enhance tumor progression in established malignancies and high-risk populations. Therefore, this review proposes a reframing that methyl donors may not be evaluated merely as protective or harmful, but rather as context-dependent modifiers whose influence is shaped by timing, metabolic status, and the underlying biology of the target tissue. Such a shift is promising for advancing precision nutrition and the prevention or targeted suppression of cancer. Full article

In animals and humans, nutrients influence signaling cascades, transcriptional programs, chromatin dynamics, and mitochondrial function, collectively shaping traits related to growth, immunity, reproduction, and stress resilience. This review synthesizes evidence supporting nutrient-mediated regulation of DNA methylation, histone modifications, non-coding RNAs, and mitochondrial biogenesis, and emphasizes their integration within metabolic and developmental pathways. Recent advances in epigenome-wide association studies (EWAS), single-cell multi-omics, and systems biology approaches have revealed how diet composition and timing can reprogram gene networks, sometimes across generations. Particular attention is given to central metabolic regulators (e.g., PPARs, mTOR) and to interactions among methyl donors, fatty acids, vitamins, and trace elements that maintain genomic stability and metabolic homeostasis. Nutrigenetic evidence further shows how genetic polymorphisms (SNPs) in loci such as IGF-1, MSTN, PPARs, and FASN alter nutrient responsiveness and influence traits like feed efficiency, body composition, and egg quality, information that can be exploited via marker-assisted or genomic selection. Mitochondrial DNA integrity and oxidative capacity are key determinants of feed conversion and energy efficiency, while dietary antioxidants and mitochondria-targeted nutrients help preserve bioenergetic function. The gut microbiome acts as a co-regulator of host gene expression through metabolite-mediated epigenetic effects, linking diet, microbial metabolites (e.g., SCFAs), and host genomic responses via the gut–liver axis. Emerging tools such as whole-genome and transcriptome sequencing, EWAS, integrated multi-omics, and CRISPR-based functional studies are transforming the field and enabling DNA-informed precision nutrition. Integrating genetic, epigenetic, and molecular data will enable genotype-specific feeding strategies, maternal and early-life programming, and predictive models that enhance productivity, health, and sustainability in poultry production. Translating these molecular insights into practice offers pathways to enhance animal welfare, reduce environmental impact, and shift nutrition from empirical feeding toward mechanistically informed precision approaches. Full article

This review article focuses on the role of choline in ovarian follicular development, regulated by nutrient–epigenetic interactions. Choline, a key feed additive, participates in DNA methylation and steroid hormone synthesis via its methyl donor function. However, its role in follicular hierarchy and maturation is unclear. Research lacks an understanding of species-specific choline metabolism, follicular fluid methylation dynamics, and toxicity thresholds. This study combines animal nutrition, epigenetics, and reproductive endocrinology. Using in vitro follicle culture models, metabolomics analysis, and cytochrome P450 family 19 subfamily A member 1 (CYP19a1) methylation site screening, it reveals that choline regulates follicle hierarchy through the betaine-S-adenosylmethionine (SAM) pathway. Proper dietary choline reduces homocysteine (HCY) and boosts CYP19a1 demethylation, enhancing theca cell estradiol (E₂) production and accelerating follicle maturation. In contrast, inadequate or excessive choline causes mesoderm-specific transcript (MEST) gene methylation abnormalities or trimethylamine N-oxide (TMAO)-mediated β-oxidation inhibition, increasing follicle atresia. A phenomenon of steroidogenic factor 1 (SF-1) methylation has been observed in poultry, showing that choline affects offspring egg-laying persistence by altering the adrenal–ovarian axis DNA methylation imprint. Future research should establish a precise choline supply system based on the HCY/TMAO ratio in follicular fluid and the CYP19a1 methylation map to improve animal reproduction. Full article

Methyl groups can be obtained either from the diet (labile methyl groups) or produced endogenously (methylneogenesis) via one-carbon (C1-) metabolism as S-adenosylmethionine (SAM). The essential nutrients folate and choline (through betaine) are metabolically entwined to feed their methyl groups into C1-metabolism. A choline-deficient diet in rats produces a 31–40% reduction in liver folate content, 50% lower hepatic SAM levels, and a doubling of plasma homocysteine. Similarly, folate deficiency results in decreased total hepatic choline. Thus, sufficient intakes of both folate and choline (or betaine) contribute to safeguarding the methyl balance in the body. A significant amount of choline (as phosphatidylcholine) is produced in the liver via the SAM-dependent phosphatidylethanolamine methyltransferase. Experimental studies using diets deficient in several methyl donors have shown that supplemental betaine was able to rescue not only plasma betaine but also plasma folate. Fasting plasma homocysteine concentrations are mainly determined by folate intake or status, while the effect of choline or betaine on fasting plasma homocysteine is minor. This appears to contradict the finding that approximately 50% of cellular SAM is provided via the betaine-homocysteine methyltransferase (BHMT) pathway, which uses dietary choline (after oxidation to betaine) or betaine to convert homocysteine to methionine and then to SAM. However, it has been shown that the relative contribution of choline and betaine to cellular methylation is better reflected by measuring plasma homocysteine after a methionine load test. Choline or betaine supplementation significantly lowers post-methionine load homocysteine, whereas folate supplementation has a minor effect on post-methionine load homocysteine concentrations. This review highlights the interactions between folate and choline and the essentiality of choline as a key player in C1-metabolism. We further address some areas of interest for future work. Full article

Choline has been recognized as an essential nutrient involved in various physiological functions critical to human health. Adequate daily intake of choline has been established by the US National Academy of Medicine in 1998, considering choline requirements for different ages, sex differences and physiological states (e.g., pregnancy). By serving as a precursor for acetylcholine and phospholipids, choline is important for cholinergic transmission and the structural integrity of cell membranes. In addition, choline is involved in lipid and cholesterol transport and serves as a methyl donor after oxidation to betaine. Extracellular choline is transported across the cell membrane via various transport systems (high-affinity and low-affinity choline transporters) with distinct features and roles. An adequate dietary intake of choline during pregnancy supports proper fetal development, and throughout life supports brain, liver, and muscle functions, while choline deficiency is linked to disease states like fatty liver. Choline has important roles in neurodevelopment, cognition, liver function, lipid metabolism, and cardiovascular health. While its signaling role has been considered mostly indirect via acetylcholine and phosphatidylcholine which are synthesized from choline, emerging evidence supports a role for choline as an intracellular messenger acting on Sigma-1R, a non-opioid intracellular receptor. These new findings expand the cell signaling repertoire and increase the current understanding of the role of choline while warranting more research to uncover the molecular mechanisms and significance in the context of GPCR signaling, the relevance for physiology and disease states. Full article

Epigenetic modifications act as crucial regulators of gene activity and are influenced by both internal and external environmental factors, with diet being the most impactful external factor. On the other hand, cellular metabolism encompasses a complex network of biochemical reactions essential for maintaining cellular function, and it impacts every cellular process. Many metabolic cofactors are critical for the activity of chromatin-modifying enzymes, influencing methylation and the global acetylation status of the epigenome. For instance, dietary nutrients, particularly those involved in one-carbon metabolism (e.g., folate, vitamins B12 and B6, riboflavin, methionine, choline, and betaine), take part in the generation of S-adenosylmethionine (SAM), which represents the main methyl donor for DNA and histone methylation; α-ketoglutarate and ascorbic acid (vitamin C) act, respectively, as a co-substrate and cofactor for Ten-eleven Translocation (TET), which is responsible for DNA demethylation; and metabolites such as Acetyl-CoA directly impact histone acetylation, linking metabolism of the TCA cycle to epigenetic regulation. Further, bioactive compounds, such as polyphenols, modulate epigenetic patterns by affecting methylation processes or targeting epigenetic enzymes. Since diet and nutrition play a critical role in shaping epigenome functions and supporting human health, this review offers a comprehensive update on recent advancements in metabolism, epigenetics, and nutrition, providing insights into how nutrients contribute to metabolic balance, epigenome integrity maintenance and, consequently, disease prevention. Full article

Betaine, a naturally occurring compound primarily derived from sugar beet by-products, has attracted increasing attention for its multifaceted roles in human and animal nutrition. Acting as both an osmolyte and a methyl group donor, betaine contributes to cellular hydration, methylation balance, antioxidant defense, and metabolic regulation. This review provides a comprehensive overview of betaine’s biological functions and its health-promoting effects across species. In humans, betaine supports hepatic function, cardiovascular health, renal protection, and physical performance, mainly by modulating homocysteine metabolism, lipid profiles, and oxidative stress. In animal production systems, it enhances growth, feed efficiency, reproductive performance, and resilience to heat stress, with species-specific applications in monogastrics, ruminants, aquaculture species, and companion animals. The review also explores the molecular mechanisms underlying betaine’s effects, including epigenetic regulation and mitochondrial function, and presents updated evidence on its biosynthesis, bioavailability, and nutrient interactions. Furthermore, the use of betaine derived from agro-industrial by-products aligns with the principles of the circular economy, promoting the sustainable reuse of valuable compounds within the agri-food chain. Despite promising findings, further research is needed to standardize effective dosages and clarify species-specific responses under different physiological and environmental conditions. Overall, betaine emerges as a promising and sustainable functional ingredient with wide-ranging applications in nutrition and health. Full article

Telomere attrition is a hallmark of cellular aging, influenced by oxidative stress, chronic inflammation, and metabolic dysregulation. Emerging evidence suggests that dietary patterns rich in plant-based, minimally processed foods may influence telomere dynamics, potentially extending healthspan. This narrative review synthesizes current literature on the molecular mechanisms by which specific nutrients—such as antioxidants, polyphenols, omega-3 fatty acids, and methyl donors—affect telomere length and telomerase activity. Conversely, high consumption of ultra-processed foods (UPFs) has been associated with accelerated telomere shortening and dysfunction, likely due to increased oxidative stress, inflammation, and nutrient deficiencies. We propose a tiered dietary intervention model including preventive, therapeutic, and regenerative phases, tailored to individual aging trajectories and physiological statuses. This model emphasizes the consumption of whole plant foods, functional bioactives, and the reduction of UPFs to preserve telomere integrity. Implementing such dietary strategies may offer a viable approach to mitigate age-related cellular decline and promote healthy aging. Full article

Guanidinoacetic acid (GAA) has been used in ruminant feeding, but it is still unclear whether the exogenous addition of methyl donors, such as methionine (Met), can enhance the effects of GAA. This study investigated the effects of dietary GAA alone or combined with Met on beef cattle growth performance and explored the underlying mechanisms via blood analysis, liver metabolomics, and transcriptomics. Forty-five Simmental bulls (453.43 ± 29.05 kg) were assigned to three groups for 140 days: CON (control), GAA (0.1% GAA), and GAM (0.1% GAA + 0.1% Met), where each group consisted of 15 bulls. Compared with the CON group, the average daily gain (ADG) and feed conversion efficiency (FCE) of the two feed additive groups were significantly increased, and the digestibility of neutral detergent fiber (NDF) was improved (p < 0.05). Among the three treatment groups, the GAM group showed a higher rumen total volatile fatty acids (TVFAs) content and digestibility of dry matter (DM) and crude protein (CP) in the beef cattle. The serum indices showed that the contents of indicators related to protein metabolism, lipid metabolism, and creatine metabolism showed different increases in the additive groups (p < 0.05). It is worth noting that the antioxidant indexes in the serum and liver tissues of beef cattle in the two additive groups were significantly improved (p < 0.05). The liver metabolites related to protein metabolism (e.g., L-asparagine, L-glutamic acid) and lipid metabolism (e.g., PC (17:0/0:0)) were elevated in two additive groups, where Met further enhanced the amino acid metabolism in GAM. In the two additive groups, transcriptomic profiling identified significant changes in the expression of genes associated with protein metabolism (including PIK3CD, AKT3, EIF4E, HDC, and SDS) and lipid metabolism (such as CD36, SCD5, ABCA1, APOC2, GPD2, and LPCAT2) in the hepatic tissues of cattle (p < 0.05). Overall, the GAA and Met supplementation enhanced the growth performance by improving the nutrient digestibility, serum protein and creatine metabolisms, antioxidant capacity, and hepatic energy and protein and lipid metabolisms. The inclusion of Met in the diet was shown to enhance the nutrient digestibility and promote more efficient amino acid metabolism within the liver of the beef cattle. Full article

Background: Prenatal alcohol exposure (PAE) can reduce fetal growth and cause neurodevelopmental disability. Prenatal choline supplements attenuate PAE-induced behavioral and growth deficits; however, the underlying mechanisms are unknown. Alcohol alters nutrient metabolism and potentially increases nutrient needs. Here, we investigate how alcohol affects choline metabolism in the maternal–fetal dyad and the role of supplemental choline. Methods: Pregnant C57BL/6J mice were assigned to one of four groups: alcohol-exposed (3 g/kg alcohol/day) or control +/− 100 mg/kg choline daily from embryonic day (E)8.5–17.5. We performed an exploratory hypothesis-generating analysis of targeted metabolomics on choline-related metabolites in the maternal liver, plasma, placenta, and fetal brain at E17.5 and Spearman correlation analyses to determine their association with gestational and fetal growth outcomes. Results: Although choline levels were largely unaffected by alcohol or choline, alcohol increased many lipid products in the CDP–choline pathway; this was not normalized by choline. Alcohol increased placental CDP–ethanolamine and reduced the maternal hepatic SAM/SAH ratio as well as dimethylglycine and the serine/glycine ratio across the dyad, suggesting a functional insufficiency in methyl donor pools. These outcomes were rescued by supplemental choline. Correlation analyses among choline metabolites and fetal growth outcomes suggest that maternal plasma methionine, serine, and the serine/glycine ratio may be predictive of maternal–fetal choline status. Conclusions: The increased hepatic lipid synthesis that characterizes chronic alcohol exposure may draw choline into phospholipid biosynthesis at the expense of its use as a methyl donor. We propose that PAE increases choline needs, and that its supplementation is necessary to fulfill these competing demands for lipid and methyl use. Full article

Background/Objectives: Folate and B12, among other B vitamins, are methyl donors and contribute to multiple DNA methylation processes. Maternal deficiency of these nutrients may be associated with impaired fetal growth, affecting the nutritional status and adiposity of the newborn. This study aimed to describe maternal folate and B12 status throughout pregnancy and evaluate its association with neonatal nutritional status. Methods: We studied 90 healthy pregnant women and their babies from the prospective OBESO cohort (Mexico City). Serum folate and B12 concentrations were measured (ELISA) in the first and third trimesters of pregnancy. Deficiency was considered if serum folate was <4 ng/mL, red blood cell folate (RBC) < 151 ng/mL, active B12 < 40 pmol/L, and total B12 < 203 pg/mL). Maternal supplementation of these nutrients was recorded. Newborn assessment (24–72 h) included weight (BW), length (L), waist circumference (WC), and fat mass percentage (%FM; air-displacement plethysmography). Newborn nutritional status indexes were computed and interpreted (BMI/age and length/age) (term-WHO, preterm-Intergrowth). Mean differences, correlations, and multiple linear and logistic regressions were performed (SPSS v. 29). Results: One-third of women had total vitamin B12 deficiency at the end of pregnancy; no folate deficiency was observed. High doses for both folic acid and B12 supplementation were identified in the third trimester (2057.04 ± 2100.74 μg/d and 7.35 ± 4.56 μg/d). Higher first- and third-trimester maternal active B12 concentrations predicted higher WC and reduced the risk of LBW. Higher first-trimester Thcy levels increased the risk of stunting. Higher third-trimester total B12 and folate concentrations predicted higher WC; the latter was associated with higher FM% at birth. Conclusions: Maternal folate, B12, and Thcy levels influence newborn nutritional status alterations, including adiposity markers. It is vital to guarantee an optimal and balanced maternal B-complex status throughout pregnancy. Full article

Globally, cognitive impairment (CI) is the leading cause of disability and dependency among the elderly, presenting a significant public health concern. However, there is currently a deficiency in pharmacological interventions that can effectively cure or significantly reverse the progression of cognitive impairment. Methyl donor nutrients (MDNs), including folic acid, choline, and vitamin B12, have been identified as potential enhancers of cognitive function. Nevertheless, there remains a dearth of comprehensive research investigating the connection between the dietary intake of MDNs and CI. In our study, we comprehensively assessed the relationship between MDNs’ dietary intake and CI in older adults, utilizing 16S rRNA gene sequencing to investigate the potential underlying mechanisms. The results showed an obvious difference in the methyl-donor nutritional quality index (MNQI) between the dementia (D) group and the dementia-free (DF) group. Specifically, there was a lower MNQI in the D group than that in the DF group. For the gut microbiome, the beta diversity of gut flora exhibited higher levels in the high methyl-donor nutritional quality (HQ) group as opposed to the low methyl-donor nutritional quality (LQ) group, and lower levels in the D group in comparison to the DF group. Subsequently, we performed a correlation analysis to examine the relationship between the relative abundance of microbiota, the intake of MDNs, and Montreal Cognitive Assessment (MoCA) scores, ultimately identifying ten genera with potential regulatory functions. Additionally, KEGG pathway analyses suggested that the one-carbon metabolism, chronic inflammation, and DNA synthesis potentially serve as pathways through which MDNs may be promising for influencing cognitive function. These results implied that MDNs might have the potential to enhance cognitive function through the regulation of microbiota homeostasis. This study offers dietary recommendations for the prevention and management of CI in the elderly. Full article

Pregnancy represents a stage during which maternal physiology and homeostatic regulation undergo dramatic change and adaptation. The fundamental purpose of these adaptations is to ensure the survival of her offspring through adequate nutrient provision and an environment that is tolerant to the semi-allogenic foetus. While poor maternal diet during pregnancy is associated with perturbed maternal adaptations during pregnancy, the influence of paternal diet on maternal well-being is less clearly defined. We fed C57BL/6 male mice either a control (CD), low protein diet (LPD), a high fat/sugar Western diet (WD) or the LPD or WD supplemented with methyl donors (MD-LPD and MD-WD, respectively) for a minimum of 8 weeks prior to mating with C57BL/6 females. Mated females were culled at day 17 of gestation for the analysis of maternal metabolic, gut, cardiac and bone health. Paternal diet had minimal influences on maternal serum and hepatic metabolite levels or gut microbiota diversity. However, analysis of the maternal hepatic transcriptome revealed distinct profiles of differential gene expression in response to the diet of the father. Paternal LPD and MD-LPD resulted in differential expression of genes associated with lipid metabolism, transcription, ubiquitin conjugation and immunity in dams, while paternal WD and MD-WD modified the expression of genes associated with ubiquitin conjugation and cardiac morphology. Finally, we observed changes in maternal femur length, volume of trabecular bone, trabecular connectivity, volume of the cortical medullar cavity and thickness of the cortical bone in response to the father’s diets. Our current study demonstrates that poor paternal diet at the time of mating can influence the patterns of maternal metabolism and gestation-associated adaptations to her physiology. Full article

Choline is an essential nutrient, with high requirements during fetal and postnatal growth. Tissue concentrations of total choline are tightly regulated, requiring an increase in its pool size proportional to growth. Phosphatidylcholine and sphingomyelin, containing a choline headgroup, are constitutive membrane phospholipids, accounting for >85% of total choline, indicating that choline requirements are particularly high during growth. Daily phosphatidylcholine secretion via bile for lipid digestion and very low-density lipoproteins for plasma transport of arachidonic and docosahexaenoic acid to other organs exceed 50% of its hepatic pool. Moreover, phosphatidylcholine is required for converting pro-apoptotic ceramides to sphingomyelin, while choline is the source of betaine as a methyl donor for creatine synthesis, DNA methylation/repair and kidney function. Interrupted choline supply, as during current total parenteral nutrition (TPN), causes a rapid drop in plasma choline concentration and accumulating deficit. The American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) defined choline as critical to all infants requiring TPN, claiming its inclusion in parenteral feeding regimes. We performed a systematic literature search in Pubmed with the terms “choline” and “parenteral nutrition”, resulting in 47 relevant publications. Their results, together with cross-references, are discussed. While studies on parenteral choline administration in neonates and older children are lacking, preclinical and observational studies, as well as small randomized controlled trials in adults, suggest choline deficiency as a major contributor to acute and chronic TPN-associated liver disease, and the safety and efficacy of parenteral choline administration for its prevention. Hence, we call for choline formulations suitable to be added to TPN solutions and clinical trials to study their efficacy, particularly in growing children including preterm infants. Full article