Euterpe oleracea Mart. (açaí) is a widely consumed botanical supplement marketed for antioxidant, anti-inflammatory, and antiproliferative properties. Despite its popularity, limited data exist on its ability to modulate drug-metabolizing enzymes and transporters—critical determinants of pharmacokinetic botanical-drug interactions. This study evaluated the cytotoxicity and induction potential of açaí extracts on cytochrome P450 (CYP450) enzymes and drug transporters using physiologically relevant in vitro models. Test samples included aqueous, acidic methanol, methanol, and ethanol extracts of açaí berry powder (Mountain Rose) and commercial capsules (Nature’s Way, Natrol), selected to reflect consumer products and enhance translational relevance. Cytotoxicity was assessed using CellTiter-Glo® luminescent assay in sandwich-cultured human hepatocytes. Induction of CYP1A2, CYP2B6, CYP3A4, P-glycoprotein (P-gp), and organic anion transporting polypeptides (OATP1B1/B3) was evaluated at the mRNA level via RT-qPCR in the same hepatocyte model. Functional transporter activity was assessed using intracellular probe accumulation assays in LS174T human colon carcinoma cells, a complementary model for preliminary screening. A time- and dose-dependent reduction in hepatocyte viability occurred with specific extracts, notably MRAC (acidic methanol), MRME (methanol), MRET (ethanol), and F4AC (acidic methanol, Natrol). However, none significantly induced CYP450 or transporter expression. Preliminary functional assays also showed minimal impact on P-gp and OATP activity. While preliminary, this study provides a comprehensive evaluation of açaí-mediated modulation of key pharmacokinetic pathways and underscores the need for rigorous assessment of botanical extracts to better predict potential botanical-drug interactions.

Demand for high-quality and standardized phytochemicals (botanicals) and plant extracts if rising in both the food and dietary supplement industries. Ensuring the authenticity of the plant raw materials used in botanical and dietary supplement manufacturing is an important step before processing raw materials. However, authenticating phytochemicals (botanicals) are challenging due to their unique characteristics, including geographical location, seasonal variations, environmental conditions, and plant diversity. These factors cause variability in properties, making consistent authentication methods difficult to establish. The current review is centered on the utilization of multisource and qualitative methods for authenticating the identity of botanical and food ingredients. This review highlights the integral role of various botanicals and plant extracts authentication methods such as micro/macroscopy, chromatography, and spectroscopy technology, including DNA-based approaches. Further summarizing the current state of knowledge and importance its potential contributions to the field of botanical ingredient authentication system. This study also highlights the plants used in dietary supplement categories of weight management, memory enhancement and blood sugar regulation and their adulteration/admixture. Furthermore, discusses considerations for selecting appropriate methods and optimization steps in the implementation and standardization of botanical and plant extract authentication. In addition, we discussed the challenges and opportunities associated with the implementation and standardization of botanical and plant extracts authentication system. The future of botanical authentication will be shaped by advances in molecular diagnostics such as targeted DNA barcoding, Next-Generation Sequencing (NGS), and chemometric integration with spectroscopic techniques which are set to greatly enhance accuracy, traceability, and global compliance in botanical product safety and quality.

Yeast beta-glucans demonstrate immune-modulating effects; however, few studies have explored the potential of yeast beta-glucans to enhance immune response to vaccination. This pilot study aimed to assess the adjuvant effect of a yeast beta-glucan supplementation on antibody titer response to influenza vaccination. Adults (n = 90; 70.7 ± 10.1 years) were recruited over two vaccination seasons and randomized to receive 500 mg of beta-glucan or placebo (500 mg cellulose) daily in a double-blind study design. Pre- and 4 wk post-vaccination serum influenza-specific antibody titers were assessed using an optimized Hemagglutination Inhibition (HI) assay. Plasma cytokines 24 h post-vaccination were quantified by immunoassay. Cold and flu symptoms, using the Modified Jackson Criteria, fever, and self-perceived fatigue were monitored daily. Linear mixed models were used to test for differences in the fixed effects of time, treatment, and their interactions. In season 1 (Fall 2022), despite a baseline suggesting seroprotection for the Influenza A (H3N2 A/Wisconsin/67/2005) in 92% of the beta-glucan group and 74% of the placebo group, the post-vaccination antibody titer response (Δ = 95.8) favored beta-glucan over placebo (p = 0.037). Influenza B/Austria/1359417/2021 antigen demonstrated poor detection; 7 of the 10 HI detectible antibody responses seen were in the beta-glucan group. In season 2 (Fall 2023), the Influenza A (H1N1 A/Victoria/4897/2022) antigen demonstrated poor detection (14%), which precluded further cohort analyses. Of the cytokines, interferon-gamma (IFN-γ) increased similarly in both groups after vaccination, not supporting the adjuvant action of beta-glucan at the cellular level. Reported cold and flu symptoms were low in both groups and did not differ. Overall, the findings suggest that yeast beta-glucan supplementation may elicit a greater change in antibody titer to seasonal influenza vaccination. However, confirmation is needed with a larger sample of older adults and with follow-up to assess protection from disease. Clinical trial registry number and website: https://clinicaltrials.gov/study/NCT05074303.

Vitamin E is an effective treatment for metabolic dysfunction-associated steatohepatitis (MASH) but associated with hemorrhagic complications when used for other indications. We aimed to determine the risk of developing iron deficiency during treatment of metabolic dysfunction-associated steatotic liver disease (MASLD) with vitamin E. Iron status was monitored prospectively in 20 people with MASLD treated with 200 – 800 IU/d vitamin E (https://clinicaltrials.gov/study/NCT01792115). To gain mechanistic insights liver histology, hepatic gene expression, hepatic 4-hydroxynonenal, haptoglobin genotype and plasma vitamin E levels were assessed. We found iron deficiency to occur in 11/20 subjects (55%) after a median 11 weeks (range 4-13) of vitamin E treatment, and anemia to occur in 6 of the 11 (30% of study population) after 23 weeks (16-36). Ferritin (84.5 ± 85.2 to 47.8 ± 54.9μg/L, p < 0.001) and mean corpuscular volume (MCV, 86.2 ± 4.9 to 84.3±4.3fL, p = 0.003) significantly decreased, with a concomitant rise in red-cell distribution width (RDW, 13.4 ± 1.3 to 14.4 ± 1.9%, p = 0.003). A gastrointestinal bleeding source was found in 75% of subjects with complete work-up. Iron deficiency occurred in all diabetics vs. 47% of non-diabetics (p 0.007). Iron deficiency risk was not associated with cirrhosis, platelet count, prothrombin time, haptoglobin genotype, or plasma vitamin E level. Changes in hepatic gene expression and oxidative stress were suggestive of an extrahepatic effect. Iron deficiency resolved with appropriate care even with continued vitamin E treatment. We conclude that occult gastrointestinal bleeding and iron deficiency were frequently observed during vitamin E treatment, possibly reflecting an effect on platelet function. Close monitoring is warranted during the first months of treatment, especially in diabetics and subjects with risk factors for gastrointestinal bleeding.

The scientific evidence supporting recommendations for dietary supplement use to prevent or treat coronavirus disease 2019 (COVID‑19) is not well‑established. This cohort study investigates the relationship between dietary supplement usage and COVID‑19 symptoms among 27,181 adults tested for COVID‑19. Using data from surveys following COVID‑19 testing, conducted by the University of Arkansas for Medical Sciences, associations between dietary supplement usage, symptomatology, and COVID‑19 status were explored. The prevalence of supplement consumption among symptomatic individuals was significant, with non‑Hispanic (NH)‑White individuals showing higher usage rates. Among those testing positive for COVID‑19, mainly asymptomatic cases, dietary supplement usage was increased (7.8%), suggesting a proactive approach to supplementation. Symptomatic individuals with confirmed COVID‑19 also showed heightened dietary supplement usage (37.9%), indicating a response to perceived therapeutic benefits. Notably, respiratory symptoms such as cough (46.2%), fever (31.4%), and shortness of breath (8.9%) correlated consistently with increased dietary supplement usage across different time points. Despite limitations such as varying test sensitivities and potential selection biases, this study offers valuable insights into individual health‑seeking behaviors during the pandemic. Findings emphasize the importance of targeted public health interventions and education to address disparities in dietary supplement usage and promote evidence‑based approaches to dietary supplementation. Further research is warranted to understand better the motivations and implications of dietary supplement usage in the context of the pandemic.

Modafinil (brand name Provigil®) is a Schedule IV (U.S.) drug used for the treatment of narcolepsy and sleep disorders. It is also known to be used recreationally. Analogs of modafinil, including adrafinil, remain unapproved and/or unscheduled. The lack of scheduling has made these analogs a popular target for recreational use and inclusion in dietary supplements. However, the use of controlled substances (or their analogs) without the care of a physician presents a public health risk. Preliminary nontargeted analyses in our laboratory revealed the presence of adrafinil in several dietary supplements, highlighting the need for an analytical method to identify modafinil analogs in supplements. A liquid chromatography high resolution mass spectrometry (LC-HRMS) method was developed and validated to quantitate modafinil, plus four novel unscheduled modafinil analogs: adrafinil, CRL-40,940, CRL-40,941, and N-methyl-4,4-difluoromodafinil. This method was then applied to four samples of products marketed as dietary supplements collected via undercover purchase. These four products were marketed as nootropics or cognitive enhancers and labeled to contain adrafinil. Adrafinil was found in all four samples. The identification of modafinil analogs in this context is important so that consumers are not, knowingly or unknowingly, consuming these active pharmaceutical ingredients in products marketed as dietary supplements.

The market for olive leaf dietary supplements is expanding rapidly and is valued at $437.15 million today. However, information on the control of these products is sketchy and the origin and variety of olives are rarely stated. The aim of this research was to validate a simple and rapid screening method for oleuropein determination in olive leaf dietary supplements. A matrix blank was prepared by removal of oleuropein from a mixture of dietary supplements and the matrix was then spiked with known concentrations to create a spiked matrix calibration curve in the range 5 - 40% oleuropein. Five replicate extractions and analyses of the matrix standards were carried out over 10 days. Precision was less than 6% RSD and linearity was demonstrated by the Fischer test. Extraction recovery was > 90% and there was a strong linear relationship between authentic and matrix standards. All tested products conformed to the label claim which was strongly correlated with total polyphenols measured by the Folin-Ciocalteau method. Antioxidant activity was measured by the DPPH assay and was found to be strongly correlated with total phenol content and oleuropein concentration.

Caffeic acid is a common phenolic acid found in coffee and numerous fruits and vegetables. Known for its antioxidant properties, it is widely used as a dietary supplement as part of a polyphenol mixture or as an extract in the form of a capsule or powder. It is also available in liquid form as a homeopathic supplement. Caffeic acid phenethyl ester (CAPE) is an active component of propolis produced by honey bees. Propolis extract is used as a supplement and is available in various forms. The present paper is a comprehensive review of the biomedical literature, showing that caffeic acid effects are hormetic and occur in numerous biological models and cell types for a broad range of endpoints including many aging-related processes. Hormesis is a biphasic dose/concentration response displaying a low concentration/dose stimulation and a high concentration/dose inhibition. Complex alternative search strategies for caffeic acid were used since publications rarely used the terms hormesis or hormetic. Evaluation of the data provides the first assessment of caffeic acid-induced hormetic concentration/dose responses and their quantitative features. Their mechanistic foundations, extrapolative strengths/limitations, and their biomedical, clinical, and public health implications are discussed. Suggestions for future research are presented.

The rampant use of antibiotics has led to the emergence of multidrug resistance and is often coupled with gut dysbiosis. To circumvent the harmful impact of antibiotics, probiotics have emerged as an effective intervention. However, while the new probiotics are being added to the list, more recently, the nature and role of their counterparts, viz. prebiotics, postbiotics and parabiotics have also drawn considerable attention. As such, intricate relationships among these gut-biotics vis-à-vis their role in imparting health benefits is to be delineated in a holistic manner. Prebiotic dietary fibers are selectively fermented by probiotics and promote their colonization in the gut. The proliferation of probiotics leads to production of fermentation by-products (postbiotics) which affect the growth of enteropathogens by lowering the pH and producing inhibitory bacteriocins. After completing life-cycle, their dead remnants (parabiotics e.g. exopolysaccharides and cell wall glycoproteins) also inhibit adhesion and biofilm formation of pathogens on the gut epithelium. These beneficial effects are not just endemic to gut but a systemic response is witnessed at different gut-organ axes. Thus, to decipher the role of probiotics, it is imperative to unravel the interdependence between these components. This review elaborates on the recent advancements on various aspects of these gut-biotics and the mechanism of potential attributes like anti-oxidant, anti-inflammatory, anti-neoplastic, anti-lipidemic and anti-hyperglycemic benefits.