BackgroundDietary supplements that combine vitamins, minerals, phytonutrients, prebiotics, and probiotics have gained popularity among health-oriented consumers seeking convenient ways to fill nutritional gaps and support gut health.MethodsThis randomized, double-blind, placebo-controlled crossover study examined the effects of two weeks of the nutritional supplement (AG1®) on gut microbial composition, nutritional adequacy, and tolerability. Twenty resistance-trained men (n = 10; 26.4 ± 6.5 y) and women (n = 10; 26.9 ± 5.3 y) supplemented daily with either AG1® or placebo (PL) for 14 days. Following a 2-week washout, participants crossed over to the other condition. Participants provided stool samples for gut microbial composition analysis, completed the Digestion-associated Quality of Life Questionnaire (DQLQ), and completed a 24-h dietary intake assessment at the beginning and end of each 14-day supplementation period. Outcomes were analyzed using repeated-measures and multivariate statistical approaches for dietary intake, gut microbiota, metabolomics, and questionnaire data.ResultsAG1® did not produce large, global shifts in microbial alpha or beta diversity, supplementation was associated with selective enrichment of key bacterial taxa commonly linked to gut health, including Lactiplantibacillus plantarum, Lacticaseibacillus rhamnosus, and Bifidobacterium animalis. AG1® supplementation significantly improved nutritional adequacy by increasing the total number of micronutrient Estimated Average Requirements (EARs) met compared to placebo (2.8; p = 0.0011), with no significant differences in digestive quality of life between groups (p = 0.777). Vitamins A, C, and E were the most common nutrient gaps filled by AG1 supplementation.ConclusionsTwo weeks of AG1® supplementation improved micronutrient adequacy in healthy resistance-trained adults by reducing nutrient gaps. Supplementation also selectively enriched key beneficial gut microbial taxa and putative microbial functional without inducing major disruptions to overall community structure. Importantly, AG1® was well tolerated and did not negatively impact digestion-associated quality of life.Clinical trial registrationClinicalTrials.gov, identifier: NCT06521424.

Background/objectives:Nutrient interactions in multi-ingredient supplements may influence micronutrient absorption and bioavailability, yet pharmacokinetic data exploring these interactions remains generally limited. This clinical trial assessed the acute absorption phase of key micronutrients in AG1, a comprehensive nutritional supplement containing vitamins, minerals, probiotics, and phytochemicals. Methods:In a randomized, double-blind, placebo-controlled crossover trial 16 healthy adults (8 males and 8 females) consumed a single serving (13 g) of AG1 or a taste- and appearance-matched placebo mixed in water, following a 10-h overnight fast. Each condition was separated by a 1-week washout period. Blood samples were collected 0 (baseline), 30, 60, 90, 120, 180, 240, 360, and 480 min post-ingestion. Plasma concentrations of folate, calcium, zinc, vitamin C, biotin, nicotinamide, pyridoxine, riboflavin, thiamine, and hesperidin were measured. The absorption phase was generally characterized using area under the curve (AUC0-480 min), Cmax, and Tmax. Safety and tolerability were assessed throughout the study. Statistical analysis included repeated-measures ANOVA and paired t-tests. Results:AG1 significantly increased AUC0-480 min values (p < 0.05) for all measured nutrients except pyridoxine which revealed a weak trend (p = 0.1205). Both AG1 and placebo were well tolerated, with no serious adverse events reported. Conclusion:Acute consumption of AG1 resulted in measurable increases in circulating levels of most of the tested micronutrients, indicating effective absorption. These findings suggest that AG1 may influence nutrient status in healthy adults. Clinical trial registration:Clinicaltrials.gov, identifier NCT06316700.

Nutrient interactions in multi-ingredient supplements may influence absorption and bioavailability, yet pharmacokinetic data in this context remains limited. This clinical trial assessed the post-prandial absorption kinetics of key micronutrients in AG1, a comprehensive supplement containing vitamins, minerals, probiotics, and phytonutrients. In a randomized, double-blind, placebo-controlled crossover trial 16 healthy adults (8 males and 8 females) consumed a single serving (13g) of AG1 or a taste- and appearance-matched placebo mixed in water, following a 10-hour overnight fast. Each condition was separated by a 1-week washout. Blood samples were collected pre-consumption and at 30, 60, 90, 120, 180, 240, 360, and 480 minutes post-ingestion. Plasma concentrations of folate, calcium, zinc, vitamin C, biotin, nicotinamide, pyridoxine, riboflavin, thiamin, and hesperidin were measured. Area under the curve (AUC 0-480 min ) was used to assess nutrient absorption. Safety and tolerability were assessed throughout the study. Statistical analysis included repeated measures ANOVA and paired t-tests. AG1 significantly increased AUC 0-480 min values (p<0.05) for all measured nutrients except pyridoxine which revealed a strong trend (p = 0.075) and hesperidin (p = 0.224). Both AG1 and placebo were well tolerated, with no serious adverse events reported. Acute consumption of AG1 resulted in measurable increases in circulating levels of most of the tested micronutrients, indicating effective absorption and bioavailability. These findings support the potential of AG1 to contribute meaningfully to nutritional status and overall health.

Background In a multistage series of experiments designed to assess the efficacy of AG1® supplementation, we performed a randomized controlled clinical trial to assess the effects of daily AG1 consumption on clinical blood safety parameters in healthy adults over 12 weeks.Methods A randomized, triple-blind, placebo-controlled parallel clinical trial was conducted in 120 healthy adults (41 ± 10 years). Participants agreed to maintain their usual diet for the entire study (assessed by ASA24®). Participants were randomly assigned to consume AG1 powder (13 g) or a placebo powder (maltodextrin, matched for appearance and taste) mixed in 8 oz of water for 12 weeks. Fasting blood samples were collected at baseline (PRE) and following 12 weeks of daily supplementation (POST) of their assigned treatment to assess markers of renal, hepatic, metabolic, and overall health [Complete Blood Count (CBC), Comprehensive Metabolic Panel (CMP), lipid panel, clinical hematological markers]. Self-reported adverse events were also monitored to assess the incidence rates of other potential side effects.Results Of the participants randomized, 105 adults completed PRE and POST blood testing (41 ± 10 years; n = 28 males). There were no significant differences in the participants’ dietary intake outside of the assigned treatments. Two-way (treatment group × time) ANCOVAs revealed no significant (p > 0.05) effects on any clinical blood safety markers with no adverse events reported for either treatment.Conclusions AG1® consumption over 12 weeks did not adversely affect renal, hepatic, or other safety markers in healthy adults. Additionally, no adverse events were reported.

Background Inadequate intake of micronutrients is common even among active, resistance-trained individuals. Supplementation with a foundational nutrition supplement (AG1®) may promote adequate intake of key micronutrients, close nutrient gaps, and improve diet quality.Methods In a randomized, double-blind, placebo-controlled crossover design, this study evaluated the effect of daily AG1 supplementation on nutritional adequacy in 20 resistance-trained men (n = 10; 26.4 ± 6.5 y; 174.5 ± 9.8 cm; 85.8 ± 9.6 kg; 10.3 ± 7.9 y resistance training experience [RTE]) and women (n = 10; 26.9 ± 5.3 y; 163.8 ± 8.7 cm; 66.1 ± 13.0 kg; 9.1 ± 5.4 y RTE). Participants supplemented daily with AG1 or placebo for 14 days. Following a 2-week washout, participants crossed over to the other condition. Participants completed a 24-hour dietary intake assessment at the start (baseline) and end of each 14-day supplementation period (endpoint) using the Automated Self-Administered 24-Hour Dietary Assessment Tool (ASA24®). Nutrient gaps were defined as the difference between an individual’s reported dietary intake and established dietary targets [the Estimated Average Requirements (EARs) for specific nutrients]. Sixteen micronutrients were included in the assessment based on the following criteria: micronutrients were present in the study product, could be measured by ASA24®, and had an EAR. The combined nutrient gap score was determined by adding the nutrient intakes that met the EAR, with each micronutrient meeting the EAR counting as 1, for a total maximum score of 16. Nutrient values from AG1 or placebo were added to the respective endpoint diets, and a nutrient gap score was computed to determine the impact of each treatment. Data were analyzed using 2-way analysis of variance and Fishers’s LSD test for multiple comparisons.Results All 20 participants completed baseline and endpoint recalls and were included in the nutrient gap analysis. At baseline, the AG1 and placebo groups met 13.9 ± 2.5 and 12.8 ± 2.8 out of 16 nutrient EARs, respectively with no significant difference between groups (p > 0.05). Following the intervention, AG1 significantly increased the total number of EARs met compared to placebo [2.8 (95% CI: 1.1, 4.4); p = 0.0011]. Within the AG1 group, 1.4 (95% CI: 0.3, 2.5) nutrient gaps were closed on average compared to −0.2 (95% CI: −1.3, 0.9) in the placebo group. Vitamins A, C, and E were the most common nutrient gaps filled by AG1 supplementation.Conclusions AG1® consumption significantly improved nutrient adequacy by reducing nutrient gaps in healthy resistance-trained adults.

Modulation of the human gut microbiome has become an area of interest in the nutraceutical space. We explored the effect of the novel foundational nutrition supplement AG1® on the composition of human microbiota in an in vitro experimental design. Employing the Simulator of Human Intestinal Microbial Ecosystem (SHIME®) model, AG1® underwent digestion, absorption, and subsequent colonic microenvironment simulation under physiologically relevant conditions in healthy human fecal inocula. Following 48 h of colonic simulation, the gut microbiota were described using shallow shotgun, whole genome sequencing. Metagenomic data were used to describe changes in community structure (alpha diversity, beta diversity, and changes in specific taxa) and community function (functional heterogeneity and changes in specific bacterial metabolic pathways). Results showed no significant change in alpha diversity, but a significant effect of treatment and donor and an interaction between the treatment and donor effect on structural heterogeneity likely stemming from the differential enrichment of eight bacterial taxa. Similar findings were observed for community functional heterogeneity likely stemming from the enrichment of 20 metabolic pathways characterized in the gene ontology term database. It is logical to conclude that an acute dose of AG1 has significant effects on gut microbial composition that may translate into favorable effects in humans.

Background This study aimed to examine the effect of a commercially available multi-ingredient powder (AG1 (R)) on the gut microbiome and assess the impact of AG1 (R) on GI tolerability and other clinical safety markers in healthy men and women. Methods Using a double-blind, randomized, two-arm, placebo-controlled, parallel design, we examined a 4-week daily supplementation regimen of AG1 (R) vs. placebo (PL). Fifteen men and 15 women provided stool samples for microbiome analysis, questionnaires for digestive quality of life (DQLQ), and completed visual analog scales (VAS) and Bristol stool charts to assess stool consistency and bowel frequency before and after the 4-week intervention. Participant's blood work (CBC, CMP, and lipid panel) was also assessed before and after the 4-week intervention. Alpha diversity was determined by Shannon and Chao1 index scores and evaluated by a two-way ANOVA, beta diversity in taxonomic abundances and functional pathways was visualized using partial least squares-discriminant analyses and statistically evaluated by PERMANOVA. To identify key biomarkers, specific feature differences in taxonomic relative abundance and normalized functional pathway counts were analyzed by linear discriminant analysis (LDA) effect size (LEfSe). Questionnaires, clinical safety markers, and hemodynamics were evaluated by mixed factorial ANOVAs with repeated measures. This study was registered on clinicaltrials.gov (NCT06181214). ResultsAG1 (R) supplementation enriched two probiotic taxa (Lactobacillus acidophilus and Bifidobacterium bifidum) that likely stem from the probiotics species that exist in the product, as well as L. lactis CH_LC01 and Acetatifactor sp900066565 ASM1486575v1 while reducing Clostridium sp000435835. Regarding community function, AG1 (R) showed an enrichment of two functional pathways while diminishing none. Alternatively, the PL enriched six, but diminished five functional pathways. Neither treatment negatively impacted the digestive quality of life via DQLQ, bowel frequency via VAS, or stool consistency via VAS and Bristol. However, there may have been a greater improvement in the DQLQ score (+62.5%, p = 0.058, d = 0.73) after four weeks of AG1 (R) supplementation compared to a reduction (-50%) in PL. Furthermore, AG1 (R) did not significantly alter clinical safety markers following supplementation providing evidence for its safety profile. Conclusions: AG1 (R) can be consumed safely by healthy adults over four weeks with a potential beneficial impact in their digestive symptom quality of life.

Research examining the changes in muscle oxygen saturation across multiple sets of resistance exercise is limited. The purpose of this study was to describe the physiological response of muscle oxygenation parameters during upper-body resistance exercise and examine the differential effects of relevant participant characteristics on resistance training performance and muscle oxygen saturation dynamics. Sixty-one recreationally trained men (n = 44; 21.8 ± 2.6 years) and women (n = 17; 20.2 ± 1.8 years) completed five-repetition maximum sets of barbell bench presses at a load equal to 75% 1-RM with a 2 min rest interval. Muscle oxygen saturation (SmO2) dynamics within the anterior deltoid were monitored using a portable near-infrared spectroscopy sensor. The percent change in SmO2 (∆%SmO2), the muscle oxygen re-saturation rate (SmO2RecSlope), and the highest measured SmO2 value during recovery periods (SmO2Peak) were measured. Two-way (sex [men, women] x time [sets 1–5]) repeated measures analyses of variance (ANOVA) were performed on muscle saturation variables. To examine the effect of relevant controlling variables, separate analyses of covariance (ANCOVA) with repeated measures were also performed. No differences were seen with ∆%SmO2 across sets. The main effects for sets occurred for SmO2RecSlope, whereby a decline was noted on sets 4 and 5 (p = 0.001) compared to set 1. Additionally, SmO2Peak was the lowest on set 5 (p < 0.001) compared to all other sets. Moreover, body mass (p = 0.013), diastolic blood pressure (p = 0.044), and mean arterial pressure (p = 0.033) for ∆%SmO2 were the only significant covariates noted amongst the muscle oxygenation variables. In conclusion, no sex differences and only a few set differences in muscle oxygen saturation dynamics were seen without employing any covariates. Body mass, diastolic blood pressure, and mean arterial pressure were identified as factors that could influence observed responses.

Position Statement: The International Society of Sports Nutrition (ISSN) bases the following position stand on an analysis of the literature regarding the effects of β-Hydroxy-β-Methylbutyrate (HMB). The following 12 points have been approved by the Research Committee of the Society: 1. HMB is a metabolite of the amino acid leucine that is naturally produced in both humans and other animals. Two forms of HMB have been studied: Calcium HMB (HMB-Ca) and a free acid form of HMB (HMB-FA). HMB-FA appears to lead to increased appearance of HMB in the bloodstream when compared to HMB-Ca, though recent results are mixed. 2. The available safety/toxicity data suggest that chronic HMB-Ca and HMB-FA consumption are safe for oral HMB supplementation in humans up to at least one year. 3. There are no negative effects of HMB-Ca and HMB-FA on glucose tolerance and insulin sensitivity in humans. There may be improvements in glucose metabolism in younger adults. 4. The primary mode of action of HMB appears to be through its dual mechanism to enhance muscle protein synthesis and suppress muscle protein breakdown. HMB's activation of mTORC1 is independent of the leucine-sensing pathway (Sestrin2-GATOR2 complex). 5. HMB may help reduce muscle damage and promote muscle recovery, which can promote muscle growth/repair. HMB may also have anti-inflammatory effects, which could contribute to reducing muscle damage and soreness. 6. HMB consumption in close proximity to an exercise bout may be beneficial to increase muscle protein synthesis and attenuate the inflammatory response. HMB can provide a beneficial physiological effect when consumed both acutely and chronically in humans. 7. Daily HMB supplementation (38 mg/kg body weight) in combination with exercise training may improve body composition through increasing lean mass and/or decreasing fat mass with benefits in participants across age, sex, and training status. The most pronounced of these improvements in body composition with HMB have been observed in studies with robust resistance training programs and dietary control. 8. HMB may improve strength and power in untrained individuals, but its performance benefits in trained athletes are mixed and increase with an increase in study duration (>6 weeks). HMB's beneficial effects on athletic performance are thought to be driven by improved recovery. 9. HMB supplementation appears to potentially have a positive impact on aerobic performance, especially in trained athletes. The mechanisms of the effects are unknown. 10. HMB supplementation may be important in a non-exercising sedentary and aging population to improve muscle strength, functionality, and muscle quality. The effects of HMB supplementation with exercise are varied, but the combination may have a beneficial effect on the treatment of age-associated sarcopenia under select conditions. 11. HMB may be effective in countering muscle disuse atrophy during periods of inactivity due to illness or injury. The modulation of mitochondrial dynamics and lipid metabolism by HMB may be a potential mechanism for preventing disuse atrophy and aiding rehabilitation beyond HMB's effects on rates of muscle protein synthesis and degradation. 12. The efficacy of HMB in combination with certain nutrients may be enhanced under select conditions.

Metabolomics is a critical approach to fully understand the metabolic repercussions of a nutritional supplement on the gut microbiota. Here, a proof of principle study was conducted via a metabolomic survey of polar metabolites to explore the effect of AG1 on the metabolic output of the human gut microbiota, in vitro, using the Simulator of the Human Intestinal Microbial Ecosystem® (SHIME). Aliquots were isolated from the fecal slurry at baseline (0 h), 1 h, 24 h, and 48 h of colonic fermentation simulation. Chemical analysis at these timepoints detected a total of 165 metabolites with 57, 21, and 14 specific metabolites being significantly altered by AG1 relative to the blank controls at 1 h, 24 h, and 48 h, respectively. Many of these metabolites likely resulted from AG1 directly as a supplement, but several of these metabolites also likely arose specifically from microbial metabolism.

Nutritional interventions to reduce gastrointestinal (GI) permeability are of significant interest to physically active adults and those experiencing chronic health conditions. This in vitro study was designed to assess the impact of AG1, a novel synbiotic, on GI permeability following an inflammatory challenge. Interventions [AG1 (vitamins/minerals, pre-/probiotics, and phytonutrients) and control (control medium)] were fed separately into a human GI tract model (stomach, small intestine, and colon). In the colonic phase, the GI contents were combined with fecal inocula from three healthy human donors. GI permeability was evaluated with transepithelial electrical resistance (TEER) in a Caco-2 (apical)/THP1-Blue™ (basolateral) co-culture model. The apical side received sodium butyrate (positive control) or Caco-2 complete medium (negative control) during baseline testing. In the 24 h experiment, the apical side received colonic simulation isolates from the GI model, and the basolateral side was treated with Caco-2 complete medium, then 6 h treatment with lipopolysaccharide. TEER was assessed at 0 h and 24 h, and inflammatory markers were measured at 30 h in triplicate. Paired samples t-tests were used to evaluate endpoint mean difference (MD) for AG1 vs. control. TEER was higher for AG1 (mean ± SD: 99.89 ± 1.32%) vs. control (mean ± SD: 92.87 ± 1.22%) following activated THP1-induced damage [MD: 7.0% (p < 0.05)]. AG1 maintained TEER similar to the level of the negative control [−0.1% (p = 0.02)]. No differences in inflammatory markers were observed. These in vitro data suggest that acute supplementation with AG1 might stimulate protective effects on GI permeability. These changes may be driven by SCFA production due to the pre-/probiotic properties of AG1, but more research is needed.

Nutrient synergy refers to the concept that the combined effects of two or more nutrients working together have a greater physiological impact on the body than when each nutrient is consumed individually. While nutrition science traditionally focuses on isolating single nutrients to study their effects, it is recognized that nutrients interact in complex ways, and their combined consumption can lead to additive effects. Additionally, the Dietary Reference Intakes (DRIs) provide guidelines to prevent nutrient deficiencies and excessive intake but are not designed to assess the potential synergistic effects of consuming nutrients together. Even the term synergy is often applied in different manners depending on the scientific discipline. Considering these issues, the aim of this narrative review is to investigate the potential health benefits of consuming different nutrients and nutrient supplements in combination, a concept we define as nutrient synergy, which has gained considerable attention for its impact on overall well-being. We will examine how nutrient synergy affects major bodily systems, influencing systemic health. Additionally, we will address the challenges associated with promoting and conducting research on this topic, while proposing potential solutions to enhance the quality and quantity of scientific literature on nutrient synergy.

Synbiotics, a combination of prebiotics and probiotics, are growing in popularity, with consumers desiring improved gastrointestinal health. Prebiotics are non-digestible nutrients that can be metabolized by microbiota to exert a beneficial effect, while probiotics are live microorganisms that can also exert beneficial effects when consumed. Due to the rise in prebiotic and probiotic usage, there has been concern from some experts that not all synbiotics indicated for use as nutritional supplements are properly evaluated for their biological efficacy. AG1 is a novel foundational nutrition supplement that has been designed to exert a synbiotic effect. In its formulation, AG1 contains traditional prebiotics, phytonutrients from wholefood sources and botanical extracts, and two probiotics (Lactobacillus acidophilus UALa-01 and Bifidobacterium bifidum UABb-10). Alongside ingredients evidence that AG1 exerts synbiotic effects, efficacy testing was performed using the Simulator of Human Intestinal Microbial Ecosystem (SHIME®) model. Physical and metabolic evidence of fermentation were used to evaluate the success of AG1 as a synbiotic. Data from the SHIME® model showed a significant increase (p < 0.01) in the total amount of short chain fatty acids (SCFAs), specifically with significant increases in total acetate (p < 0.001) and propionate (p < 0.0001) production, as well as gas production. These results were expected, as both SCFAs and gas are the major byproducts of bacterial carbohydrate fermentation. These data suggest that AG1 exerts preclinical evidence of a synbiotic effect by human microbiota.

The measurement of intestinal permeability is important for diagnoses of diseases of the gastrointestinal tract, such as Crohn’s disease. The gold standard for measurement of intestinal permeability is the dual sugar absorption test, which measures the urinary or blood concentrations of two orally administered sugars, a monosaccharide and a disaccharide, over a period of time. The lining of the small intestine allows monosaccharides to cross into the bloodstream, but the larger disaccharide is not permitted to cross the intestine unless the barrier is compromised. The permeability of the lining is measured by a ratio between select monosaccharides and disaccharides, and this indicates the overall status of the small intestine. In order to study the effects of resistance exercise on intestinal permeability in human subjects, we developed a liquid chromatography tandem mass spectrometry (LC–MS/MS) method for the analysis of saccharides in blood plasma. The analytes included rhamnose, a monosaccharide not commonly found in food, and lactulose, a disaccharide. A trisaccharide, raffinose, was used as an internal standard. The method was robust, and had consistent reliability.

Nitric-oxide-stimulating dietary supplements are widely available and marketed to strength athletes and weightlifters seeking to increase muscle performance and augment training adaptations. These supplements contain ingredients classified as nitric oxide (NO) precursors (i.e., "NO boosters"). Endogenous NO is generated via a nitric oxide synthase (NOS)-dependent pathway and a NOS-independent pathway that rely on precursors including L-arginine and nitrates, with L-citrulline serving as an effective precursor of L-arginine. Nitric oxide plays a critical role in endothelial function, promoting relaxation of vascular smooth muscle and subsequent dilation which may favorably impact blood flow and augment mechanisms contributing to skeletal muscle performance, hypertrophy, and strength adaptations. The aim of this review is to describe the NO production pathways and summarize the current literature on the effects of supplementation with NO precursors for strength and power performance. The information will allow for an informed decision when considering the use of L-arginine, L-citrulline, and nitrates to improve muscular function by increasing NO bioavailability.

Background Systematic reviews and meta-analyses related to high-intensity functional training (HIFT) have been conducted. However, due to a restricted pool of available research, these investigations are often limited in scope. As such, a scoping review investigating the present literature surrounding the acute physiological response to HIFT-based exercise was chosen as a more appropriate structured review. Methodology A scoping review was conducted following Arksey and O’Malley’s framework. Three large scale databases were searched to reveal any article pertaining to HIFT and related exercise terminology. Results A total of 2,241 articles were found during the initial search. Following this, titles, then abstracts, and full-texts were reviewed to determine inclusion eligibility. A total of 60 articles which investigated a combined total of 35 unique HIFT workouts were included within this review. Conclusions A variety of physiological parameters and HIFT workouts have been examined. Markers of intensity (e.g., blood lactate concentrations, heart rate) have been most consistently assessed across all studies, and these support the idea that HIFT workouts are typically performed at high-intensity. In contrast, the inclusion of most other measures (e.g., hormonal, markers of inflammation and damage, energy expenditure, performance) has been inconsistent and has thus, limited the possibility for making generalized conclusions. Differences in study methodologies have further impacted conclusions, as different studies have varied in sample population characteristics, workouts assessed, and time points. Though it may be impossible to comprehensively research all possible HIFT workouts, consistent adoption of population definitions and workload quantification may overcome this challenge and assist with future comparisons.