There is no comprehensive review of the evidence to support omega-3 polyunsaturated fatty acids (PUFAs) as a relatively safe and tolerable intervention. This study aimed to provide a meta-analytic and comprehensive review on the adverse effects of all kinds of ω-3 PUFA supplementation reported in randomized controlled trials (RCTs) in human subjects. A systematic review of RCTs published between 1987 and 2023 was carried out based on searches of 8 electronic databases. All RCTs that compared the adverse effects of ω-3 PUFAs containing eicosapentaenoic acid, docosahexaenoic acid, or both compared with controls (a placebo or a standard treatment) were included. The primary outcome was the adverse effects related to ω-3 PUFA prescription. A total of 90 RCTs showed that the ω-3 PUFA group, when compared with the placebo, had significantly higher odds of occurrence of diarrhea (odds ratio [OR] = 1.257, P = 0.010), dysgeusia (OR = 3.478, P < 0.001), and bleeding tendency (OR = 1.260, P = 0.025) but lower rates of back pain (OR = 0.727, P < 0.001). The subgroup analysis showed that the prescription ω-3 PUFA products (RxOME3FAs) had higher ω-3 PUFA dosages than generic ω-3 PUFAs (OME3FAs) (3056.38 ± 1113.28 mg/d compared with 2315.92 ± 1725.61 mg/d), and studies on RxOME3FAs performed more standard assessments than OME3FAs on adverse effects (63% compared with 36%). There was no report of definite ω-3 PUFA-related serious adverse events. The subjects taking ω-3 PUFAs were at higher odds of experiencing adverse effects; hence, comprehensive assessments of the adverse effects may help to detect minor/subtle adverse effects associated with ω-3 PUFAs. This study was registered at PROSPERO as CRD42023401169.

Malnutrition is prevalent in people with upper gastrointestinal (GI) cancers and is associated with shorter survival and poor quality of life. In order to effectively prevent or treat malnutrition, nutrition interventions must ensure appropriate energy provision to meet daily metabolic demands. In practice, the energy needs of people with cancer are frequently estimated from predictive equations which are not cancer-specific and are demonstrated to be inaccurate in this population. The purpose of this scoping review was to synthesize the existing evidence regarding energy expenditure in people with upper GI cancer. Three databases (Ovid MEDLINE, Embase via Ovid, CINAHL plus) were systematically searched to identify studies reporting on resting energy expenditure using indirect calorimetry and total energy expenditure using doubly labeled water (DLW) in adults with any stage of upper GI cancer at any point from diagnosis. A total of 57 original research studies involving 2,125 individuals with cancer of the esophagus, stomach, pancreas, biliary tract, or liver were eligible for inclusion. All studies used indirect calorimetry, and one study used DLW to measure energy expenditure, which was reported unadjusted in 42 studies, adjusted for body weight in 32 studies, and adjusted for fat-free mass in 13 studies. Energy expenditure in upper GI cancer was compared with noncancer controls in 19 studies and measured compared with predicted energy expenditure reported in 31 studies. There was heterogeneity in study design and in reporting of important clinical characteristics between studies. There was also substantial variation in energy expenditure between studies and within and between cancer types. Given this heterogeneity and known inaccuracies of predictive equations in patients with cancer, energy expenditure should be measured in practice wherever feasible. Additional research in cohorts defined by cancer type, stage, and treatment is needed to further characterize energy expenditure in upper GI cancer.

Nutrient profiling (NP) models are useful for characterizing the healthfulness of foods and for underpinning various nutrition-related public health strategies. Recently, there has been a rapid increase in the number of NP models developed by different organizations worldwide. A systematic review (SR) summarizing the key characteristics of NP models with applications in government-led nutrition policies was carried out in 2016 and published by Labonté et al. [4]. Given the continuous proliferation of NP models, the current study aimed to update this SR. Systematic searches were performed in databases of both the peer-reviewed (n = 7) and grey (n = 1) literature to identify publications related to NP published between May 2016 and September 2020. The full text of relevant publications was assessed independently by 2 reviewers to build a list of potential models. Each model was classified as "already identified in the original SR" or as "newly identified." The eligibility of the "newly identified" models, and of some models excluded from the previous SR because their details were not known at that time, were then assessed independently by 2 reviewers based on pre-established criteria. A total of 151 potential NP models were assessed for eligibility, of which 93 were "newly identified," 28 were originally excluded from the previous SR, and 30 were identified from additional online searches during the eligibility assessment stage. Twenty-six models met the inclusion criteria. Their most frequent applications were food labeling (n = 17) and regulation of food marketing to children (n = 7). They all included nutrients to limit, with sodium, saturated fat, and total sugars being the most frequently considered. Content or face validity testing was conducted for 11 (42%) of the included models. As NP models are increasingly used worldwide to support public health strategies, having an up-to-date resource listing them and detailing their characteristics is crucial. PROSPERO #CRD42021259041.

According to published meta-analyses, vitamin D exerts different beneficial effects in preventing and controlling risk factors associated with noncommunicable chronic diseases; however, the results are still conflicting. The purpose of this umbrella meta-analysis was to investigate the effect of vitamin D supplementation on low-density lipoprotein cholesterol, high-density lipoprotein (HDL) cholesterol, total cholesterol (TC), and triglyceride (TG) as components of the lipid profile. PubMed, Scopus, Web of Science, and Cochrane Database of Systematic Reviews were systematically searched for meta-analyses of randomized controlled trials. The umbrella meta-analysis followed the PRISMA guidelines. The random-effects model was employed to estimate the overall effect size (ES). Overall, 25 meta-analyses were included. In the standardized mean difference analysis, vitamin D significantly decreased TG (ES: -0.15; 95% CI: -0.23, -0.08; P ≤ 0.001) and TC levels (ES: -0.17; 95% CI: -0.23, -0.11; P ≤ 0.001) and increased HDL levels (ES: 0.08; 95% CI: 0.01, 0.15; P = 0.025). In the weighted mean difference analysis, vitamin D significantly decreased only TG levels (ES: -4.63 mg/dL; 95% CI: -7.70, -1.57; P = 0.003). The present study supports that vitamin D supplementation could be considered a beneficial adjuvant therapy in managing lipid profile levels, especially in individuals with vitamin D deficiency. This systematic review was registered in PROSPERO as CRD42022306334.

Vitamin A deficiency (VAD) increases risk for morbidity and mortality. Food-based approaches offer one strategy to improve vitamin A status. This systematic review assessed evidence of the effects of food-based approaches on the vitamin A status of women and children under 5 y. VAD was defined as clinical ocular symptoms, such as loss of vision, and/or retinol plasma or serum concentration <0.70 μmol/L. Searches on food-based approaches to improve vitamin A status were conducted for the period 2011-2022 on PubMed, CINHAL, Web of Science, and Google Scholar using PRISMA guidelines. English-language publications were included. Case studies, unpublished dissertations, and non-peer-reviewed studies were excluded. This review comprises 24 of 27,322 identified studies; 23 included studies focused on provitamin A carotenoids. There were 17,214 participants across the 24 studies with sample sizes ranging from 8 to 3571 individuals. Intervention studies spanned from 3 wk to 2 y. Fifteen (63%) studies were randomized control trials, 7 were cross-sectional, and 2 were longitudinal studies. Most studies (N = 21) used biochemical measurements, for example, serum retinol, to assess vitamin A status; other studies used clinical symptoms (for example, xerophtalmia) or dietary intake. Thirteen (54%) studies reported a statistically significant effect of food-based interventions (N = 8) or an association of diet (N = 5) on vitamin A status. This systematic review indicated that some food-based interventions improved vitamin A status, thus offering a safe and effective delivery mechanism for vitamin A. There appeared to be significant association between vitamin A status and consumption of foods with high concentrations of preformed vitamin A and provitamin A carotenoids. Differences across studies in regard to the period of evaluation, food approaches used, and statistical power may explain the lack of effectiveness of food-based approaches on vitamin A status in some studies.

Micronutrient deficiencies result in a broad range of adverse health and functional consequences, but the true prevalence of specific deficiencies remains uncertain because limited information is available from nationally representative surveys using recommended biomarkers. The present review compares various reported national deficiency prevalence estimates for nutrients and years where the estimates overlap for individual countries that conducted nationally representative surveys and explores possible reasons for any discrepancies discovered. Nationally representative micronutrient status surveys that were conducted since 2000 among preschool-aged children or women of reproductive age and included assessment of iron, vitamin A, or zinc status based on recognized biomarkers were considered eligible for inclusion, along with any modeled deficiency prevalence estimates for these same countries and years. There was considerable variation across different published prevalence estimates, with larger inconsistencies when the prevalence estimate was based on proxies, such as hemoglobin for iron deficiency and dietary zinc availability for zinc deficiency. Numerous additional methodological issues affected the prevalence estimates, such as which biomarker and what cutoff was used to define deficiency, whether the biomarker was adjusted for inflammation, and what adjustment method was used. For some country-years, the various approaches resulted in fairly consistent prevalence estimates. For other country-years, however, the results differed markedly and changed the conclusions regarding the existence and severity of the micronutrient deficiency as a public health concern. In conclusion, to determine micronutrient status, we consider the assessment of one of the recommended biomarkers in a population representative survey as the best available information. If indicated, results should be adjusted for inflammation and generally acceptable cutoffs should be applied to facilitate comparisons, although individual countries may also apply nationally defined cutoffs to determine when and where to intervene. Global consensus is needed on best practices for presenting survey results and defining the prevalence of deficiency.

The importance of nicotinamide adenine dinucleotide (NAD+) in human physiology is well recognized. As the NAD+ concentration in human skin, blood, liver, muscle, and brain are thought to decrease with age, finding ways to increase NAD+ status could possibly influence the aging process and associated metabolic sequelae. Nicotinamide mononucleotide (NMN) is a precursor for NAD+ biosynthesis, and in vitro/in vivo studies have demonstrated that NMN supplementation increases NAD+ concentration and could mitigate aging-related disorders such as oxidative stress, DNA damage, neurodegeneration, and inflammatory responses. The promotion of NMN as an antiaging health supplement has gained popularity due to such findings; however, since most studies evaluating the effects of NMN have been conducted in cell or animal models, a concern remains regarding the safety and physiological effects of NMN supplementation in the human population. Nonetheless, a dozen human clinical trials with NMN supplementation are currently underway. This review summarizes the current progress of these trials and NMN/NAD+ biology to clarify the potential effects of NMN supplementation and to shed light on future study directions.

Human milk (HM) is considered the best source of nutrition for infant growth and health. This nourishment is unique and changes constantly during lactation to adapt to the physiological needs of the developing infant. It is also recognized as a potential route of transmission of some viral pathogens although the presence of a virus in HM rarely leads to a disease in an infant. This intriguing paradox can be explained by considering the intrinsic antiviral properties of HM. In this comprehensive and schematically presented review, we have described what viruses have been detected in HM so far and what their potential transmission risk through breastfeeding is. We have provided a description of all the antiviral compounds of HM, along with an analysis of their demonstrated and hypothesized mechanisms of action. Finally, we have also analyzed the impact of HM pasteurization and storage methods on the detection and transmission of viruses, and on the antiviral compounds of HM. We have highlighted that there is currently a deep knowledge on the potential transmission of viral pathogens through breastfeeding and on the antiviral properties of HM. The current evidence suggests that, in most cases, it is unnecessarily to deprive an infant of this high-quality nourishment and that the continuation of breastfeeding is in the best interest of the infant and the mother.

Sexual and gender minorities have a higher risk for health and nutrition-related disparities across the life course compared to the heterosexual or cisgender population. Experiences of stigmatization and discrimination are associated with diminished mental health quality and psychological distress, which are risk factors for developing various eating disorders. Other nutrition disparities include increased risk for food insecurity, body dissatisfaction, and weight complications, such as those experienced by the transgender population in association with gender-affirming hormone therapies. Despite the need for tailored nutrition recommendations that address the unique needs of the lesbian, gay, bisexual, transgender, queer/questioning (LGBTQ+) community, there are currently no such guidelines in North America. The purpose of this review is to summarize major LGBTQ+ nutrition disparities and highlight the need for tailored recommendations. We examine the evidence on mental health and social disparities in this group, including vulnerabilities to disordered eating, food insecurity, and healthcare provider discrimination. Importantly, we identify a scarcity of literature on dietary concerns and nutrition care guidelines for LGBTQ+ groups, including studies that address intersectionality and differences among specific gender and sexual orientations. These gaps underline the urgency of prioritizing nutrition for LGBTQ+ health needs and for developing tailored public health nutrition recommendations for this underserved population. Our review suggests that future LGBTQ+ health and nutrition research agendas should include personalized and precision nutrition, social determinants of health, diet quality, body image, and healthcare provider cultural competency and responsiveness. Moreover, the current evidence on LGBTQ+ nutrition and health will be strengthened when research studies (including clinical trials) with robust methodologies amplify inclusion and representation of this community to elucidate health and nutrition disparities in sexual and gender minorities.

Dietary metabolomics is a relatively objective approach to identifying new biomarkers of dietary intake and for use alongside traditional methods. However, methods used across dietary feeding studies vary, thus making it challenging to compare results. The objective of this study was to synthesize methodological components of controlled human feeding studies designed to quantify the diet-related metabolome in biospecimens, including plasma, serum, and urine after dietary interventions. Six electronic databases were searched. Included studies were as follows: 1) conducted in healthy adults; 2) intervention studies; 3) feeding studies focusing on dietary patterns; and 4) measured the dietary metabolome. From 12,425 texts, 50 met all inclusion criteria. Interventions were primarily crossover (n = 25) and parallel randomized controlled trials (n = 22), with between 8 and 395 participants. Seventeen different dietary patterns were tested, with the most common being the "High versus Low-Glycemic Index/Load" pattern (n = 11) and "Typical Country Intake" (n = 11); with 32 providing all or the majority (90%) of food, 16 providing some food, and 2 providing no food. Metabolites were identified in urine (n = 31) and plasma/serum (n = 30). Metabolites were quantified using liquid chromatography, mass spectroscopy (n = 31) and used untargeted metabolomics (n = 37). There was extensive variability in the methods used in controlled human feeding studies examining the metabolome, including dietary patterns tested, biospecimen sample collection, and metabolomic analysis techniques. To improve the comparability and reproducibility of controlled human feeding studies examining the metabolome, it is important to provide detailed information about the dietary interventions being tested, including information about included or restricted foods, food groups, and meal plans provided. Strategies to control for individual variability, such as a crossover study design, statistical adjustment methods, dietary-controlled run-in periods, or providing standardized meals or test foods throughout the study should also be considered. The protocol for this review has been registered at Open Science Framework (https://doi.org/10.17605/OSF.IO/DAHGS).

Research on the effects of zinc supplementation on lipid profiles in people with type 2 diabetes mellitus (T2DM) has been inconsistent. This systematic review and meta-analysis was performed to summarize the current data on the effects of zinc supplementation on lipid profiles in patients with T2DM. Three online databases including PubMed, Scopus, and Web of Science were searched to find relevant studies published until September 2022. The exposure was zinc supplementation, and the outcomes were low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride (TG), and total cholesterol (TC). Fourteen randomized clinical trials consisting of 1067 patients were included in the statistical analysis. Significant improvement was observed in all 4 lipid profile components. Following zinc supplementation, a significant decrease was observed in TC (weighted mean difference [WMD]: -16.16; 95% confidence interval [CI]: -26.43, -5.89; P = 0.002), LDL (WMD: -6.18; 95% CI: -9.35, -3.02; P < 0.001), and TG (WMD: -13.08; 95% CI: -21.83, -4.34; P = 0.003). After analyzing 13 studies reporting HDL, a significant increase was seen (WMD: 3.76; 95% CI: 1.30, 6.22; P = 0.003). In a nonlinear dose-response analysis, a significant inverse association was observed between <12 wk zinc supplementation and TC, LDL, and TG (TC: WMD: -5, Pnonlinearity < 0.001; LDL: WMD: -5, Pnonlinearity = 0.07, TG: WMD: -16.5, Pnonlinearity = 0.006). Nonlinear dose-response analysis shows that the optimum elemental zinc dosage for the best response to the supplementation for TC, LDL, and TG are 120, 100, and 140 mg/d, respectively (TC: WMD: -5, Pnonlinearity < 0.001; LDL: WMD: -10, Pnonlinearity = 0.006, TG: WMD: -50, Pnonlinearity = 0.031). In conclusion, we found significant changes in all 4 components of the lipid profile through zinc supplementation in T2DM patients. Based on our findings, zinc supplementation may have profound favorable consequences on the lipid profile of T2DM patients, especially in the zinc-deficient group.

Accumulation of deoxyribonucleic acid (DNA) damage diminishes cellular health, increases risk of developmental and degenerative diseases, and accelerates aging. Optimizing nutrient intake can minimize accrual of DNA damage. The objectives of this review are to: 1) assemble and systematically analyze high-level evidence for the effect of supplementation with micronutrients and phytochemicals on baseline levels of DNA damage in humans, and 2) use this knowledge to identify which of these essential micronutrients or nonessential phytochemicals promote DNA integrity in vivo in humans. We conducted systematic literature searches of the PubMed database to identify interventional, prospective, cross-sectional, or in vitro studies that explored the association between nutrients and established biomarkers of DNA damage associated with developmental and degenerative disease risk. Biomarkers included lymphocyte chromosome aberrations, lymphocyte and buccal cell micronuclei, DNA methylation, lymphocyte/leukocyte DNA strand breaks, DNA oxidation, telomere length, telomerase activity, and mitochondrial DNA mutations. Only randomized, controlled interventions and uncontrolled longitudinal intervention studies conducted in humans were selected for evaluation and data extraction. These studies were ranked for the quality of their study design. In all, 96 of the 124 articles identified reported studies that achieved a quality assessment score ≥ 5 (from a maximum score of 7) and were included in the final review. Based on these studies, nutrients associated with protective effects included vitamin A and its precursor β-carotene, vitamins C, E, B1, B12, folate, minerals selenium and zinc, and phytochemicals such as curcumin (with piperine), lycopene, and proanthocyanidins. These findings highlight the importance of nutrients involved in (i) DNA metabolism and repair (folate, vitamin B12, and zinc) and (ii) prevention of oxidative stress and inflammation (vitamins A, C, E, lycopene, curcumin, proanthocyanidins, selenium, and zinc). Supplementation with certain micronutrients and their combinations may reduce DNA damage and promote cellular health by improving the maintenance of genome integrity.

Accumulation of hepatic triacylglycerol (TG) is highly associated with impaired whole-body insulin-glucose homeostasis and dyslipidemia. The summarized findings from human intervention studies investigating the effect of reduced dietary carbohydrate and increased fat intake (and in studies also increased protein) while maintaining energy intake at eucaloric requirements reveal a beneficial effect of carbohydrate reduction on hepatic TG content in obese individuals with steatosis and indices of insulin resistance. Evidence suggests that the reduction of hepatic TG content after reduced intake of carbohydrates and increased fat/protein intake in humans, results from regulation of fatty acid (FA) metabolism within the liver, with an increase in hepatic FA oxidation and ketogenesis, together with a concomitant downregulation of FA synthesis from de novo lipogenesis. The adaptations in hepatic metabolism may result from reduced intrahepatic monosaccharide and insulin availability, reduced glycolysis and increased FA availability when carbohydrate intake is reduced.