An inverse relationship between saturated fatty acid (SFA) intake and Lp(a) concentration has been observed; however, there has been no quantification of this effect. The objective was to determine if SFA consumption alters Lp(a) levels among adults without atherosclerotic cardiovascular disease (ASCVD). A systematic review and meta-analysis of randomized controlled trials contrasting a lower SFA diet(s) with a higher SFA diet(s) among adults without ASCVD was conducted. PubMed, Cochrane Central Register of Clinical Trials, ClinicalTrials.gov, and Web of Science databases and registers were searched through October 2023. The standardized mean difference in Lp(a) between diets lower vs. higher in SFA (percent of energy [%E]) was determined using random-effects meta-analysis. Analyses were also conducted to examine the effect of replacing SFA with carbohydrates (CHO), monounsaturated (MUFA), polyunsaturated (PUFA), or trans fatty acids (TFAs). In total, 6,255 publications were identified in the systematic search. Twenty-six publications reporting 27 randomized controlled trials, including 1,325 participants and 49 diet comparisons, were included. The mean difference in SFA between lower vs. higher SFA diets was 7.6% E (3.7% - 17.8% E). After lower SFA diets, Lp(a) concentration was higher (SMD 0.14 [95%CI: 0.03, 0.24]) compared to higher SFA diets. Subgroup analyses showed higher Lp(a) following diets where SFA was replaced by CHO (trials=8, n=539; SMD 0.21 [95%CI: 0.02, 0.40]) or TFAs (trials=8, n=300; SMD 0.32 [95%CI: 0.17, 0.48]). No differences in Lp(a) were observed when MUFA (trials=16, n=641; SMD 0.04 [95%CI: -0.08, 0.16]) or PUFA (trials=8, n=415; SMD 0.09 [-0.04, 0.22]) replaced SFA. Lower SFA diets modestly increase Lp(a) compared to higher SFA diets among individuals without ASCVD. This effect appeared to be driven by replacement of SFA with CHO or TFA. Research investigating the atherogenicity of diet induced Lp(a) changes is needed to inform dietary management of lipid/lipoprotein disorders. (PROSPERO Registration number: CRD42020154169).

Recently, there is growing usage of prebiotics and probiotics as dietary supplements due to their purported health benefits. AG1^® (AG1) is a novel foundational nutrition supplement which contains vitamins, minerals, phytonutrients, wholefood concentrates, adaptogens, and functional mushrooms. AG1 could be classified as a synbiotic because it contains traditional and non-traditional prebiotics (e.g., inulin and phytonutrients) as well as lactic-acid-producing probiotics. The purpose of this study was to employ the Simulator of Human Intestinal Microbial Ecosystem (SHIME^®) model, which measures various aspects of gastrointestinal fermentation, to investigate the synbiotic effects of AG1. The SHIME experiment quantified gas production, changes in pH, and byproducts of carbohydrate and protein fermentation at baseline, 1, 24, and 48 h following the administration of AG1 or a blank control. The results indicated that AG1 significantly increased (p < 0.05; 41.9% increase) the production of total short-chain fatty acids (SCFAs) including acetate (p = 0.001; 49.0% increase) and propionate (p < 0.001; 70.8% increase). Regarding non-carbohydrate fermentation byproducts, AG1 produced a small but significant increase in ammonium production (p = 0.02; 5.1% increase) but did not promote significant branched-chain SCFA production. These data suggest fermentation occurred in a transplanted human colonic microbiota and these processes were enhanced by the AG1 nutritional supplement. Ultimately, AG1 showed preclinical evidence as a synbiotic given the significant increases in total SCFA production, acetate, propionate, and other metabolic byproducts of fermentation.

While traditional multivitamin and mineral (MVM) supplements generally come in tablet form, new powder forms of MVM supplements are available with theoretically higher bioavailability relative to tablet MVM supplements. The purpose of this study was to assess the bioaccessibility and bioavailability of minerals (magnesium (Mg), zinc (Zn), calcium (Ca), and potassium (K)) in a tablet MVM supplement compared to a novel powder Foundational Nutrition supplement (AG1^®), containing minerals, vitamins, phytochemicals, and pre-/probiotics, in the upper gastrointestinal tract. The tablet MVM supplement was specifically formulated for this study, with matched mineral contents and identical chemical structures. The adapted Simulator of the Human Intestinal Microbial Ecosystem (SHIME^®) model was used to assess the bioaccessibility and bioavailability of soluble minerals using a simulated upper gastrointestinal tract and dialysis membrane to mimic human digestion and absorption. The bioaccessibility was assessed at the end of the stomach and duodenum. The bioaccessibility and bioavailability were assessed at 1, 2, and 3 h following dialysis. The preliminary soluble mineral analysis of the tablet (crushed to a powder) and AG1 powder demonstrated significantly higher (p < 0.05) soluble fractions of Zn and Ca, but lower Mg in the AG1 powder vs. the tablet. The total soluble mineral percentages at the stomach and duodenum end were all significantly higher for the AG1 powder vs. the tablet (p < 0.05). Mg, Ca, and Zn were more (p < 0.05) bioaccessible and bioavailable in the powder compared to the tablet during the small intestine simulation. The bioaccessible fraction of K was higher (p < 0.05) only at 3 h for the tablet vs. the powder. These preclinical data demonstrate that the AG1 powder has superior dissolution and disintegration characteristics compared to the tablet, leading to increased bioaccessibility and bioavailability in vitro.

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.

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.

More than 57% of US adults take dietary supplements, with the most common being daily multivitamins. Daily multivitamins are typically formulated in a pill or tablet form; however, new options, including powder form that can be mixed with water, are being utilized to increase bioavailability. While limited data are available, the theory is that multivitamin tablets must be adequately dissolved before entering the small intestine for assimilation, while powders come pre-dissolved before consumption, which theoretically ensures enhanced bioavailability. Our aim was to investigate the bioaccessibility and bioavailability of minerals (magnesium (Mg), zinc (Zn), calcium (Ca), and potassium (K)) using a novel foundational nutrition supplement called AG1 compared to a multivitamin tablet. AG1 contains vitamins and minerals comparable to multivitamin tablets but also includes prebiotics, probiotics, and phytonutrients. We employed the adapted Simulator of Human Intestinal Microbial Ecosystem (SHIME^®) model to assess the bioaccessibility and bioavailability of this study’s products using a simulated stomach and small intestine physiological environment equipped with a dialysis membrane (methylcellulose) to emulate absorption. Luminal contents were collected at the end of the stomach, duodenum, and 1-, 2-, and 3 h after small intestine absorption simulation (dialysis) to assess bioaccessibility. The dialysis solution was measured at 1-, 2-, and 3 h to assess bioavailability. A significantly higher (p < 0.05) percentage of the total amount of all minerals given at the baseline was present at the end of the stomach and duodenum portion for the powder form vs. the tablet. There was a significantly higher % maximal concentration (C_max), bioavailability, and bioaccessibility for Mg, Ca, and Zn for AG1 vs. the tablet. These preclinical data demonstrate that a greater proportion of minerals in AG1 enter the small intestine, have a higher C_max, and several are more bioaccessible and bioavailable than a tablet multivitamin in vitro.