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  • New
  • Open Access Icon
  • Research Article
  • 10.3390/nu18060890
Effects of Nicotinamide Mononucleotide Supplementation on Blood Pressure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
  • Mar 11, 2026
  • Nutrients
  • Mu Zhang + 9 more

Background/Objectives: High blood pressure remains a primary modifiable risk factor for cardiovascular disease. Nicotinamide mononucleotide (NMN) has emerged as a promising supplement; however, its efficacy with respect to blood pressure in humans is unclear. This meta-analysis systematically evaluated the effects of various NMN supplements on resting systolic blood pressure (SBP) and diastolic blood pressure (DBP) in adults with elevated blood pressure. Methods: A systematic literature search was conducted to identify eligible randomized controlled trials (RCTs) using the databases PubMed/MEDLINE, Scopus, Web of Science, and EBSCO from their inception to 13 December 2025. R software was used to combine the data from the included original trials using a common-effects model. Subgroup analyses were performed based on age, baseline body mass index, geographical location, intervention duration, NMN dosage, and baseline blood pressure. Results: A total of 349 participants from 10 RCTs with 11 intervention arms were included. Compared with the placebo, NMN supplementation was associated with a statistically significant but modest reduction in resting DBP (WMD, −2.15 mmHg; 95% CI: −3.68 to −0.61). In contrast, the reduction in resting SBP was not statistically significant. Notably, subgroup analyses revealed that NMN supplementation resulted in a significant reduction in SBP specifically among participants aged 60 years and older (WMD: −3.94 mmHg; 95% CI: −7.06 to −0.82). Conclusions: Our findings provide preliminary and suggestive evidence that NMN supplementation may be associated with a small reduction in resting DBP and a modest beneficial effect on resting SBP in adults aged 60 years and older. However, the potential of NMN as a viable candidate for early-stage blood pressure management requires confirmation through long-term, large-scale, high-quality RCTs in future clinical studies.

  • New
  • Open Access Icon
  • Research Article
  • 10.3390/nu18060891
Purified Diets Lacking Fermentable Fiber Reduce Microbial Diversity, Alter Epithelial Transcriptome, and Exacerbate Colitis
  • Mar 11, 2026
  • Nutrients
  • Emma Griffith Thomas + 9 more

Background/Objectives: Dietary fibers play key roles in shaping gut microbiome and intestinal homeostasis. While purified diets offer experimental precision and reproducibility in rodent models, they omit the complex mixture of fermentable and non-fermentable fibers found in grain-based chow diets. We hypothesized that excluding fermentable fiber impairs intestinal homeostasis by reducing microbial metabolites and altering the colonic epithelial transcriptome, thereby increasing susceptibility to inflammation. Methods: Wildtype male C57BL/6 mice were maintained on either a standard grain-based chow diet or a purified low-fat diet (LFD) containing 5% non-fermentable cellulose for ten weeks. Fecal microbiomes, short-chain fatty acid (SCFA) profiles, and colonic epithelial transcriptomes were analyzed. A separate group was challenged with dextran sodium sulfate (DSS) following a five-week dietary intervention to compare colitis severity between the two diet groups. Results: Relative to mice fed the grain-based chow, those consuming the purified LFD (containing only non-fermentable cellulose) showed decreased gut microbial diversity and significantly lower SCFA levels. These changes were accompanied by marked differences in colonic epithelial cell transcriptomes. In LFD-fed mice, the top upregulated gene networks included ribosomal pathways and MHC complex protein binding, suggesting increased growth and gut inflammation. The most downregulated pathways included mineral absorption, actin and tubulin binding, and membrane organelle assembly, indicating major alterations in cellular structure and transport. LFD-fed mice also exhibited increased colonic expression of S100a9, a gut inflammation biomarker, and more severe disease symptoms when challenged with DSS compared to chow-fed mice. Conclusions: Fermentable fibers are one of the factors contributing to intestinal homeostasis and mitigating the severity of ulcerative colitis.

  • New
  • Open Access Icon
  • Research Article
  • 10.3390/nu18060889
Maternal Immune Activation Leads to Mitochondrial Dysfunction and a Social Deficit in Offspring That Is Reversed by Nicotinamide Riboside
  • Mar 11, 2026
  • Nutrients
  • Arkadiy A Bazhin + 6 more

Background: Maternal immune activation (MIA) during pregnancy is a known risk factor for several neurodevelopmental and psychiatric disorders, including schizophrenia. In rodent models, MIA is commonly induced using polyinosinic/polycytidylic acid (Poly(I/C)), a viral mimetic that activates Toll-like receptor 3 (TLR3) signaling and elicits an inflammatory response in both the dam and the fetuses. MIA results in various behavioral abnormalities in offspring, including deficits in social interaction. Recent studies have shown that MIA decreases the ability to maintain mitochondrial membrane potential (ΔΨm), the electrical component of the electrochemical gradient required for ATP production and alters mitochondrial protein expression in brain tissue isolated from adult offspring. Methods: In the present study, we monitor ΔΨm non-invasively in vivo using a previously published bioluminescence probe in juvenile and adult MIA offspring. We then investigated gene expression in the medial prefrontal cortex of MIA offspring by analyzing a previously published RNA sequencing dataset in combination with MitoCarta3.0, a comprehensive inventory of genes involved in mitochondrial function. Finally, we tested the hypothesis that this mitochondrial dysfunction contributes to the behavioral deficits observed in MIA offspring. Results: We have observed impaired ΔΨm maintenance in juvenile MIA offspring that persists into adulthood. Also, we found that MIA alters the expression of many genes associated with mitochondrial energy production. We demonstrated that nicotinamide riboside, a precursor to NAD+ known to restore ΔΨm, significantly attenuates MIA-induced social interaction deficits. Conclusions: Together, these findings highlight mitochondrial function as a promising therapeutic target for symptoms associated with schizophrenia and support the potential for drug discovery aimed at enhancing mitochondrial health.

  • New
  • Open Access Icon
  • Research Article
  • 10.3390/nu18060886
Down Syndrome and Obesity Management: Lifestyle Observations Made in the Framework of the GO-DS21 Project and Clinical Recommendations
  • Mar 11, 2026
  • Nutrients
  • Maria Gomis-González + 5 more

Introduction/background: Individuals with Down syndrome (DS) face a higher and earlier risk of overweight and/or obesity than the general population, influenced by factors like limited physical activity, suboptimal diet, stress, and sleep disorders. Despite the impact these lifestyle factors can have, there is a significant lack of robust, evidence-based guidelines for managing overweight and obesity in these individuals, particularly for the adult population. Results: Based on findings from an observational study across three European sites, within the EU Horizon-2020 GO-DS21 project, in this short communication, we highlight some key insights for developing effective prevention and management strategies for overweight and obesity in people with Down syndrome. Conclusions: In general terms, effective overweight and obesity management demands a holistic approach, integrating tailored diet and physical activity and actively addressing co-occurring health conditions. Moreover, the active participation of the family and peers is crucial for promoting sustainable healthy habits and for enhancing the overall quality of life of people with Down syndrome.

  • New
  • Open Access Icon
  • Research Article
  • 10.3390/nu18060885
The ‘Schools Don’t Waste’ Program: A Theory-Informed Participatory Intervention to Reduce Plate Waste in Public School Canteens
  • Mar 11, 2026
  • Nutrients
  • Mariusz Jaworski + 1 more

Background/Objectives: Food waste in school canteens constitutes a significant environmental, organizational, and public health challenge. Despite numerous initiatives aimed at reducing plate waste, limited evidence exists on participatory interventions grounded in coherent theoretical frameworks and implemented in real school settings. This study aimed to evaluate the effects of the Schools Don’t Waste (SDW) program, a participatory, educational, and behavioral intervention based on the Needs-Based, Learner-Centered, Behaviorally Focused (NLB) model, in reducing visually assessed plate waste in primary school canteens. Methods: A quasi-experimental pre-post design without randomization was conducted in 37 public primary schools in Warsaw during the 2024/2025 school year. The intervention consisted of four stages: baseline plate waste assessment (T1), participatory roundtable meetings (T2), implementation of educational and organizational actions (T3), and post-intervention evaluation (T4). Plate waste was assessed using a standardized five-point visual scale. Differences between T1 and T4 were analyzed at the school level using the Wilcoxon signed-rank test. Implementation fidelity and its association with food waste reduction were explored using Spearman correlations. Results: A total of 4988 meals were assessed at baseline and 4080 at follow-up. Significant reductions were observed in the proportion of completely uneaten meals (Δ = −6.10 pp; p < 0.001; r = −0.67), meals with three-quarters uneaten (Δ = −5.76; p < 0.001), and meals with half uneaten (Δ = −7.97; p = 0.002). Overall uneaten meals decreased significantly (p = 0.004). Sixty-two percent of schools demonstrated measurable improvement, although fidelity indicators were not significantly correlated with outcomes. Conclusions: Participatory, low-cost interventions integrating educational and organizational components may effectively reduce plate waste in school settings, while structural and contextual factors appear to moderate intervention effectiveness.

  • New
  • Open Access Icon
  • Research Article
  • 10.3390/nu18060878
Nutrition-Related and Self-Rated Health Outcomes Among Lottery-Assigned Residents and Individuals Waitlisted for Subsidized Rental Units in Chinatown, Boston, MA
  • Mar 10, 2026
  • Nutrients
  • Ana Maafs-Rodríguez + 6 more

Background: Housing is a social determinant of health. In 2015, a lottery assigned low-income families from a waitlist to a new subsidized building (NSB) in Chinatown, Boston, MA. In 2019–2020, we explored associations between housing status (NSB or being on waitlist) and self-rated physical and mental health; household food insecurity (FI); weekly consumption of fruits/vegetables (FV), weekly consumption of soda, and monthly consumption of fast food. Methods: Surveys were sent to NSB (n = 95) and waitlist (n = 2498) households. Logistic and linear regressions explored associations between housing status and outcomes of interest. Models were adjusted for age, sex, Asian background, household size, education, income, employment and distance to the closest food store. Results: A total of 138 respondents completed the survey (NSB = 36, waitlist = 102). Groups were demographically similar. In terms of self-reported health, most respondents reported good/better physical health (Waitlist: 62%, NSB: 60%) and good/better mental health (Waitlist: 68%, NSB: 74%). FI was prevalent among both waitlist households (63%) and NSB households (56%). FV intake was similar among NSB households (13.5 times/week) compared to waitlist households (12.8 times/week). The NSB group reported similar soda consumption (1.7 times/week) compared to the waitlist group (2.3 times/week), along with similar fast-food consumption (NSB: 2.7 times/month, Waitlist: 3.7 times/month). We found no statistically significant associations between housing status and outcomes of interest after adjusting for covariates. Conclusions: In this small sample, outcomes were not significantly different between groups. Future studies should explore mechanisms through which NSB residence affects nutrition and health, particularly in minority populations.

  • New
  • Open Access Icon
  • Research Article
  • 10.3390/nu18050869
Vitamin D Status and Sepsis Outcomes: A PRISMA-Compliant Umbrella Review and Meta-Analysis
  • Mar 9, 2026
  • Nutrients
  • Gracia Castro-Luna + 3 more

Background: Vitamin D plays an important role in immune regulation, and vitamin D deficiency has been increasingly associated with susceptibility to infection and adverse outcomes in critically ill patients. Numerous systematic reviews and meta-analyses have examined the relationship between vitamin D status, vitamin D receptor (VDR) gene polymorphisms, and sepsis; however, the evidence remains fragmented. Objective: The aim of this work was to synthesize high-level evidence on the association between vitamin D deficiency, VDR gene polymorphisms, vitamin D supplementation, and sepsis-related outcomes through a PRISMA 2020-compliant umbrella review. Methods: An umbrella review of systematic reviews and meta-analyses published between 2014 and 2025 was conducted using PubMed, PubMed Central, and journal archives. Eligible studies included adult, pediatric, and neonatal populations and evaluated sepsis incidence, mortality, disease severity, secondary outcomes, and genetic associations. Data were synthesized qualitatively due to overlap of primary studies and heterogeneity. Conceptual forest plots and funnel plots were used to summarize evidence direction and potential publication bias. Results: Nineteen systematic reviews and meta-analyses encompassing over 300 primary studies were included. Vitamin D deficiency was consistently associated with an increased risk of sepsis, higher mortality, and greater disease severity across adult and pediatric populations. Stronger associations were observed in children and neonates, including higher PRISM III scores, increased need for mechanical ventilation, and longer hospital stays. VDR gene polymorphisms were modestly but consistently associated with increased sepsis susceptibility. In contrast, vitamin D supplementation did not demonstrate a consistent reduction in sepsis risk or mortality. Conclusions: Vitamin D deficiency is a robust marker of sepsis risk, severity, and poor prognosis, whereas current evidence does not support vitamin D supplementation as an effective treatment for established sepsis.

  • New
  • Open Access Icon
  • Research Article
  • 10.3390/nu18050871
The Clinical Implications of Ashwagandha (Withania somnifera L.) with a Special Reference to Side Effects—A Review
  • Mar 9, 2026
  • Nutrients
  • Kaj Winther

Ashwagandha (Withania somnifera L.) root powder and extracts have long been used in Ayurvedic medicine to improve sleep and anxiety. Recent scientific investigations into its efficacy have shown promise for relief from anxiety, insomnia and stress and for improving the immune system. It has also been suggested that oxygen uptake in the cardiovascular system, muscle strength, cognitive function, the reproductive system and the aging process significantly benefit from ashwagandha treatment. Since the herbal remedy is taken daily by millions of people in India, China and parts of the West, it is interesting that there are very few case reports of side effects directly attributed to the treatment, suggesting that the administration of ashwagandha preparations may be safe. Currently, neither the European Medicines Agency nor the FDA considers ashwagandha as a drug or general health supplement. Therefore, ashwagandha products are marketed in the West as dietary supplements so that users may be exposed to unscrupulous vendors. In this narrative/literature review, scientific findings from basic research and human clinical trials on herbal remedies, spanning the period from 1994 to date, were critically evaluated for the purpose of highlighting knowledge gaps to provide context for new research. Such investigations will provide evidence for the efficacy and safety of ashwagandha treatment, thus making the herbal preparations more accessible to a wider audience.

  • New
  • Open Access Icon
  • Research Article
  • 10.3390/nu18050875
Almond Consumption Improves Inflammatory Profiles Independent of Weight Change: A 6-Week Randomized Controlled Trial in Adults with Obesity
  • Mar 9, 2026
  • Nutrients
  • Ayodeji Adepoju + 4 more

Background: Obesity is characterized by chronic low-grade systemic inflammation that contributes to metabolic dysfunction. Diet is a modifiable factor that can help reduce this inflammation. Nuts such as almonds are rich in unsaturated fats, and antioxidant and anti-inflammatory micronutrients, which may work synergistically to attenuate obesity-related inflammation. Hence, the objective of this study was to investigate whether daily almond consumption improves systemic inflammatory and immune markers in adults with obesity. Methods: In this randomized controlled parallel-arm trial (ClinicalTrials.gov ID NCT05530499), 69 adults (age 30–45 years) with obesity (BMI 30–45 kg/m2) were assigned to consume either 57 g/day of almonds (n = 38) or an isocaloric snack (cookie; n = 31) for six weeks. Fasting serum inflammatory cytokines, innate immune cell counts, body weight, serum glucose, insulin, lipid profile, and alpha-tocopherol were measured at baseline and week six. Dietary intake, compliance, palatability, acceptance, and appetite ratings were also assessed. Primary outcomes were analyzed using linear mixed models and baseline-adjusted linear models. Results: Subjective compliance was high in both groups, with greater acceptance of almonds (p < 0.05); however, serum alpha-tocopherol did not change. Almond consumption significantly decreased serum IL-6, TNF-α, and IFN-γ over 6 weeks compared with the cookie group (p < 0.05). No significant group differences were observed for innate immune cell counts, body weight, appetite ratings, blood pressure, or serum fasting glucose, insulin, total cholesterol (C), LDL-C, and triglycerides over six weeks. The almond group also increased intakes of monounsaturated fat, fiber, alpha-tocopherol, magnesium, zinc, and manganese, and improved diet quality indices relative to the cookie group (p < 0.05). Conclusions: Daily almond consumption for six weeks improved inflammatory cytokine profiles in adults with obesity, without changes in body weight under free-living conditions. These findings support recommending almonds as part of healthy dietary patterns to help attenuate obesity-related inflammation.

  • New
  • Open Access Icon
  • Research Article
  • 10.3390/nu18050870
The Ergogenic Potential of Succinic Acid in Exercise Performance and Post-Exercise Recovery: A Systematic Review
  • Mar 9, 2026
  • Nutrients
  • Karol Jędrejko + 8 more

Background: Succinic acid plays a central role in human energy metabolism as a key intermediate of the Krebs cycle that releases energy accumulated as guanosine triphosphate (GTP). Through its conversion via succinate dehydrogenase (SDH), succinate directly links the Krebs cycle to oxidative phosphorylation (OXPHOS), contributing to adenosine triphosphate (ATP) production. Exercise induces pronounced changes in succinate concentrations in skeletal muscle, blood, and saliva, with responses influenced by training status, exercise modality, and intensity. Objective: This systematic review evaluated the effects of succinate-containing supplements or sole-ingredient succinic acid supplementation on exercise performance and post-exercise recovery in healthy trained individuals. Methods: The review was conducted in accordance with PRISMA guidelines. PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar were searched without date restrictions. Interventional studies assessing succinate-containing supplementation with outcomes related to exercise performance or recovery were included. Methodological quality was evaluated using the Cochrane Risk of Bias 2 tool. This study was registered in advance with the International Prospective Register of Systematic Reviews (PROSPERO, CRD420251237042). Results: Six studies involving 153 participants (mean age: 23 years) met the inclusion criteria. Five of the six included studies were rated as having a high risk of bias, while the only study judged to be at low risk of bias reported no beneficial effects on exercise performance outcomes. Supplementation protocols included daily doses of 300–2040 mg for up to 21 days and a single acute dose of 30 mg/kg, with most interventions administering succinate as part of multi-ingredient formulations rather than as an isolated compound. Three studies reported ergogenic effects in direct performance metrics, including improvements in maximal oxygen uptake, oxygen consumption, anaerobic threshold power, and total work performed. Two additional studies demonstrated favorable physiological adaptations indirectly relevant to exercise performance, including improved acid-base regulation, hematological markers related to oxygen transport, and antioxidant status, although validated performance outcomes were not assessed. Substantial heterogeneity and overall methodological limitations precluded meta-analysis. Conclusions: Current evidence suggests that succinate-containing supplements or sole-ingredient succinic acid supplementation may enhance direct performance outcomes such as aerobic performance, total workload, and indirect physiological markers, e.g., acid-base balance, hematological indicators and antioxidant capacity in healthy trained individuals. However, given that the majority of included studies were at high risk of bias and the only low-risk study reported no ergogenic effects, current evidence does not provide reliable support for performance-enhancing benefits of succinate supplementation. Interpretation is further limited by the predominant use of multi-ingredient formulations, making it difficult to isolate the effects of succinic acid. While biologically plausible mechanisms exist, well-controlled trials using isolated succinic acid are required before conclusions regarding efficacy can be drawn.