This ISURA research study has just been published in the journal Metabolites. Read on for the abstract:

Background/Objectives: Berberine is a naturally occurring compound found in several plants and has been traditionally used for its various health benefits. However, its poor bioavailability limits its therapeutic potential. Berberine LipoMicel^® is a novel micellar formulation of berberine, microencapsulated within an emulsified matrix, designed to enhance bioavailability and bioactivity. This study aims to evaluate its safety, ensuring that improved bioavailability does not introduce new safety concerns. Methods: To assess its safety, a randomized, double-blind, placebo-controlled crossover study with a minimum 4-week washout period was conducted in 19 healthy participants over 30 days. The participants received 1000 mg of the treatment daily (i.e., 2 capsules/d), and their capillary blood was analyzed every week to monitor for changes in established safety markers related to liver and kidney function, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TB), creatinine, fasting glucose (GLU), HbA1c, and various electrolytes. Additionally, potential side effects were recorded through the collection of weekly health questionnaires to determine treatment tolerability. Results: Compared to placebo, no statistically significant changes in any of the safety markers related to liver or kidney health were detected. Within-group analysis revealed a significant reduction of total cholesterol (TC) in females after 30 days of Berberine LipoMicel^® treatment. Although not significant, both male and female participants showed a noticeable improvement in the mean AST, potentially signaling a hepatoprotective effect. As for tolerability, no adverse events were reported by any of the participants. Conclusions: Based on these findings, despite higher bioavailability of berberine in a newly formulated delivery system (LipoMicel^®), the treatment was found to be safe and well tolerated by human participants, with no significant deviations in blood chemistry that would indicate safety concerns over a period of 30 days.

Full article at Metabolites 2025, 15(4), 240; https://doi.org/10.3390/metabo15040240

This ISURA research study has just been published in the journal Pharmaceutics. Read on for the abstract:

Background: Silymarin, a flavonoid complex, and the main bioactive component of milk thistle (Silybum marianum), is known for its hepatoprotective properties but suffers from poor bioavailability due to its low solubility and extensive first-pass metabolism. Method: This study aimed to evaluate the pharmacokinetics and tolerability of a novel micellar milk thistle formulation designed to enhance silymarin absorption, compared to an unformulated/standard milk thistle product, in a small-scale human bioavailability trial. In a randomized, double-blinded, crossover study, 16 healthy participants received a single dose of either the micellar formulation (LipoMicel Milk Thistle; LMM) or the standard formulation (STD) at a total daily dose of 130 mg silymarin. Blood concentrations were measured over 24 h, and key pharmacokinetic parameters—maximum plasma concentration (C_max), time to reach maximum concentration (T_max), and area under the curve (AUC)—were calculated. Tolerability and safety were assessed through adverse event monitoring during the study period. Results: Results demonstrated a significant increase in bioavailability with the micellar formulation, with 18.9-fold higher C_max (95% CI: 1.9–30.7 ng/mL vs. 74.4–288.3 ng/mL; p = 0.007) and 11.4-fold higher AUC_0–24 (95% CI: 7.40–113.5 ng·h/mL vs. 178–612.5 ng·h/mL; p = 0.015). T_max was 0.5 (95% CI: 0.5–4.0) hours for the micellar formulation versus 2.5 (95% CI: 0.5–8.0) hours for the standard product (p = 0.015) indicating faster absorption of LMM. The standard formulation exhibited a significantly longer mean residence time compared to the LMM formulation (95% CI: 4.4–7.5 h vs. 2.8–4.2 h; p = 0.015). Conclusions: No adverse events or significant safety concerns were observed in either group. Compared to the standard, the micellar formulation showed superior pharmacokinetic outcomes, suggesting it may enhance silymarin’s clinical efficacy in liver health.

Full article at Pharmaceutics 2025, 17(7), 880; https://doi.org/10.3390/pharmaceutics17070880

This ISURA research study has just been published in the journal Nutrients. Read on for the abstract:

Background: Crystalline glucosamine sulfate (cGS) claims to be a stabilized form of glucosamine sulfate with a defined crystalline structure intended to enhance chemical stability. It is proposed to offer pharmacokinetic advantages over regular glucosamine sulfate (rGS) which is stabilized with potassium or sodium chloride. However, comparative human bioavailability data are limited. Since both forms dissociate in gastric fluid into constituent ions, the impact of cGS formulation on absorption remains uncertain. This pilot study aimed to compare the bioavailability of cGS and rGS using a randomized, double-blind, crossover design. Methods: Ten healthy adults received a single 1500 mg oral dose of either cGS or rGS with a 7-day washout between interventions. Capillary blood samples were collected over 24 h. Glucosamine and its metabolite concentrations were quantified by Liquid Chromatography-High Resolution Mass Spectrometry (LC-HRMS), and pharmacokinetic parameters—including maximum concentration (Cmax), time to reach Cmax (Tmax), and area under the curve (AUC)—were calculated. Results: Mean AUC0–24, Cmax, Tmax, and T½ values for glucosamine and glucosamine-6-sulfate (GlcN-6-S) were comparable between cGS and rGS. Although the AUC0–24 for glucosamine was modestly higher with rGS (18,300 ng·h/mL) than with cGS (12,900 ng·h/mL), the difference was not statistically significant (p = 0.136). GlcN-6-S exposure was also similar between formulations (rGS: 50,700 ng·h/mL; cGS: 50,600 ng·h/mL), with a geometric mean ratio of 1.39, a delayed Tmax (6–8 h) and longer half-life, consistent with its role as a downstream metabolite. N-acetylglucosamine levels remained stable, indicating potential homeostatic regulation. Conclusions: This pilot study found no significant pharmacokinetic advantage of cGS over rGS. These preliminary findings challenge claims of cGS’ pharmacokinetic superiority, although the small sample size limits definitive conclusions. Larger, adequately powered studies are needed to confirm these results.

Full article at Nutrients 2025, 17(15), 2491; https://doi.org/10.3390/nu17152491

This ISURA pilot study has just been published in the International Journal of Molecular Sciences. Read on for the abstract:

We investigated the pharmacokinetic pathway of berberine and its metabolites in vitro, in Caco-2 cells, and in human participants following the administration of dihydroberberine (DHB) and micellar berberine (LipoMicel^®, LMB) formulations. A pilot trial involving nine healthy volunteers was conducted over a 24 h period; blood samples were collected and subjected to Ultra High-Performance Liquid Chromatography–High Resolution Mass Spectrometry (UHPLC-HRMS) analyses to quantify the concentrations of berberine and its metabolites. Pharmacokinetic correlations indicated that berberrubine and thalifendine follow distinct metabolic pathways. Additionally, jatrorrhizine sulfate appeared to undergo metabolism differently compared to the other sulfated metabolites. Moreover, berberrubine glucuronide likely has a unique metabolic pathway distinct from other glucuronides. The human trial revealed significantly higher blood concentrations of berberine metabolites in participants of the DHB treatment group compared to the LMB treatment group—except for berberrubine glucuronide, which was only detected in the LMB treatment group. Similarly, results from in vitro investigations showed significant differences in berberine metabolite profiles between DHB and LMB. Dihydroberberine, dihydroxy-berberrubine/thalifendine and jatrorrhizine sulfate were detected in LMB-treated cells, but not in DHB-treated cells; thalifendine and jatrorrhizine-glucuronide were detected in DHB-treated cells only. While DHB treatment provided higher blood concentrations of berberine and most berberine metabolites, both in vitro (Caco-2 cells) and in vivo human studies showed that treatment with LMB resulted in a higher proportion of unmetabolized berberine compared to DHB. These findings suggest potential clinical implications that merit further investigation in future large-scale trials.

Full article at Int. J. Mol. Sci. 2024, 25(11), 5625; https://doi.org/10.3390/ijms25115625

A new ISURA-led research study has been published in the journal Nutrients. Here is the abstract:

The aim of this pilot study was to evaluate and compare bioavailability and safety of two Vitamin D₃ formulations (softgels) in healthy adults, at single daily doses of 1000 and 2500 IU, over a 60-day period. A total of 69 participants were initially screened for eligibility in a double-blind randomized study with a four-arm parallel design; 35 participants were randomized to treatment groups: (1) standard Vitamin D₃ 1000 IU (STD1000), (2) micellar Vitamin D₃ 1000 IU (LMD1000), (3) standard Vitamin D₃ 2500 IU (STD2500), and (4) micellar Vitamin D₃ 2500 IU (LMD2500). Serum Vitamin D concentrations were determined through calcifediol [25(OH)D] at baseline (=before treatment), at day 5, 10, and 15 (=during treatment), at day 30 (=end of treatment), and at day 45 and 60 (=during follow-up/post treatment). Safety markers and minerals were evaluated at baseline and at day 30 and day 60. The pharmacokinetic parameters with respect to iAUC were found to be significantly different between LMD1000 vs. STD1000: iAUC(5–60): 992 ± 260 vs. 177 ± 140 nmol day/L; p < 0.05, suggesting up to 6 times higher Vitamin D₃ absorption of LMD when measured incrementally. During follow-up, participants in the LMD1000 treatment group showed approx. 7 times higher Vitamin D₃ concentrations than the STD1000 group (iAUC(30–60): 680 ± 190 vs. 104 ± 91 nmol day/L; p < 0.05). However, no significant differences were found between the pharmacokinetics of the higher dosing groups STD2500 and LMD2500. No significant changes in serum 1,25(OH)₂D concentrations or other biochemical safety markers were detected at day 60; no excess risks of hypercalcemia (i.e., total serum calcium > 2.63 mmol/L) or other adverse events were identified. LMD, a micellar delivery vehicle for microencapsulating Vitamin D₃ (LipoMicel^®), proved to be safe and only showed superior bioavailability when compared to standard Vitamin D at the lower dose of 1000 IU. This study has clinical trial registration: NCT05209425.

Full Article at Nutrients 2024, 16(11), 1573; https://doi.org/10.3390/nu16111573

Researchers and scientists at ISURA successfully submited a metabolite profile of fish oil omega-3 fatty acids to Metabolites.

This study evaluated the differences in the metabolite profile of three n-3 FA fish oil formulations in 12 healthy participants: (1) standard softgels (STD) providing 600 mg n-3 FA; (2) enteric-coated softgels (ENT) providing 600 mg n-3 FA; (3) a new micellar formulation (LMF) providing 374 mg n-3 FA. The pharmacokinetics (PKs), such as the area under the plot of plasma concentration (AUC), and the peak blood concentration (Cmax) of the different FA metabolites including HDHAs, HETEs, HEPEs, RvD1, RvD5, RvE1, and RvE2, were determined over a total period of 24 h. Blood concentrations of EPA (26,920.0 ± 10,021.0 ng/mL·h) were significantly higher with respect to AUC0-24 following LMF treatment vs STD and ENT; when measured incrementally, blood concentrations of total n-3 FAs (EPA/DHA/DPA3) up to 11 times higher were observed for LMF vs STD (iAUC 0-24: 16,150.0 ± 5454.0 vs 1498.9 ± 443.0; p ≤ 0.0001). Significant differences in n-3 metabolites including oxylipins were found between STD and LMF with respect to 12-HEPE, 9-HEPE, 12-HETE, and RvD1; 9-HEPE levels were significantly higher following the STD vs. ENT treatment. Furthermore, within the scope of this study, changes in blood lipid levels (i.e., cholesterol, triglycerides, LDL, and HDL) were monitored in participants for up to 120 h post-treatment; a significant decrease in serum triglycerides was detected in participants (~20%) following the LMF treatment; no significant deviations from the baseline were detected for all the other lipid biomarkers in any of the treatment groups. Despite a lower administered dose, LMF provided higher blood concentrations of n-3 FAs and certain anti-inflammatory n-3 metabolites in human participants—potentially leading to better health outcomes. Full Article at Metabolites 2024, 14(5), 265; https://doi.org/10.3390/metabo14050265

Researchers and scientists with ISURA recently published a study that investigated a new berberine delivery system to confirm higher bioavailability and improved absorption in healthy volunteers.

Berberine is a plant-origin quaternary isoquinoline alkaloid with a vast array of biological activities, including antioxidant and blood-glucose- and blood-lipid-lowering effects. However, its therapeutic potential is largely limited by its poor oral bioavailability. The aim of this study was to investigate the in vitro solubility and Caco-2 cell permeability followed by pharmacokinetic profiling in healthy volunteers of a new food-grade berberine delivery system (i.e., Berberine LipoMicel®). X-ray diffractometry (XRD), in vitro solubility, and Caco-2 cell permeability indicated higher bioavailability of LipoMicel Berberine (LMB) compared to the standard formulation. Increased aqueous solubility (up to 1.4-fold), as well as improved Caco-2 cell permeability of LMB (7.18 × 10−5 ± 7.89 × 10−6 cm/s), were observed when compared to standard/unformulated berberine (4.93 × 10−6 ± 4.28 × 10−7 cm/s). Demonstrating better uptake, LMB achieved significant increases in AUC0–24 and Cmax compared to the standard formulation (AUC: 78.2 ± 14.4 ng h/mL vs. 13.4 ± 1.97 ng h/mL, respectively; p < 0.05; Cmax: 15.8 ± 2.6 ng/mL vs. 1.67 ± 0.41 ng/mL) in a pilot study of healthy volunteers (n = 10). No adverse reactions were reported during the study period. In conclusion, LMB presents a highly bioavailable formula with superior absorption (up to six-fold) compared to standard berberine formulation and may, therefore, have the potential to improve the therapeutic efficacy of berberine. The study has been registered on ClinicalTrials.gov with Identifier NCT05370261. Full Article at: Pharmaceutics; doi: 10.3390/pharmaceutics15112567

Researchers and scientists with ISURA recently published a pilot study that compared different formulations of quercetin with respect to variations in absorption.

Abstract: This study aimed to evaluate the blood concentrations of quercetin in healthy participants after the administration of different formulations in single- and multiple-dose phases. Ten healthy adults (males, 5; females, 5; age 37 ± 11 years) participated in a diet-controlled, crossover pilot study. Participants received three different doses (250 mg, 500 mg, or 1000 mg) of quercetin aglycone orally. In the single-dose study, blood concentrations (AUC_0–24 and C_max) of standard quercetin were compared with those of LipoMicel®—a food-grade delivery form of quercetin. In the multiple-dose study, blood concentrations of formulated quercetin were observed over 72 h, after repeated doses of LipoMicel (LM) treatments. The AUC_0–24 ranged from 77.3 to 1128.9 ng·h/ml: LM significantly increased blood concentrations of quercetin by 7-fold (LM 500) compared to standard quercetin, when tested at the same dose, over 24 h (); LM administered at a higher dose (LM 1000) achieved 15-fold higher absorption (); LM tested at half a dose of standard quercetin increased concentration by approx. 3-fold (LM 250). Quercetin blood concentrations were attained over 72 h. The major metabolites measured in the blood were methylated, sulfate, and glutathione (GSH) conjugates of quercetin. Significant differences in concentrations between quercetin conjugates (sulfate vs. methyl vs. GSH) were observed (). Data obtained from this study suggest that supplementation with LipoMicel® is a promising strategy to increase the absorption of quercetin and its health-promoting effects in humans. However, due to the low sample size in this pilot study, further research is still warranted to confirm the observations in larger populations.

Full Article at: https://doi.org/10.1155/2023/9727539

The Natural Health Products Research Society of Canada held its 19th annual conference – returning to Montreal, for a third time, for this year’s event. The University of Quebec in Montreal (UQAM) hosted the event. The conference opened with a reception at the Montreal Botanical Gardens and most of the presentations were held at the university’s downtown campus.

As in previous years, this conference brought together researchers from across the Canadian and international Natural Health Products (NHP) community with participants coming from academia, practitioner groups, industry, and government. Organisations represented included the American Botanical Council, Office of Dietary Supplements at the National Institutes of Health in the United States, the Canadian Health Food Association, Health Canada and the Council for Responsible Nutrition. The conference continued the tradition of presenting research and scientific information of the highest quality covering a wide range of topics including NHPs in health aging; NHP industry innovation; the regulation opportunities for NHP research and the challenges faced in obtaining consistent laboratory tests.

Recognising her immense contribution in the areas of botany, ecology and the importance of indigenous knowledge, the society honoured Dr. Nancy Turner, Emeritus Professor at the University of Victoria with this year’s Dr. Neil Towers Award. Her keynote lecture captured studies in these areas as well as the milestones of her career and professional life. This year, the Dr. Rogers’s sponsored presentation made by Dr. Paul Spagnuolo, from the University of Guelph, who presented his work exploring the metabolic modulation by avocado-derived bioactives in improving cancer outcomes.

As a key player in Canada, ISURA not only was a platinum sponsor but played an active role in the conference with ISURA Scientific Advisory Committee members: Dr. Mary Hardy and Michael Smith, chairing sessions on NHPs in Cancer and NHP industry innovation respectively. In addition, Dr. Hardy together with Dr. Julia Solnier, acted as judges for the student posters and presentations. Together with Lisa Lange from the Natural and Non-Prescription Health Products Directorate, Health Canada and Sonia Parmar from the Canadian Health Food Association, Michael Smith participated in a panel discussion on NHP regulation talking about the role of international regulation.

A highlight of the conference was the session sponsored by ISURA and titled New Frontiers in NHP Analysis. The session and panel discussion were chaired by Dr. Hardy and Michael Smith with two global leaders of the NHP sector, Dr. Robin Marles and Dr. Joe Betz as participants. Bringing their experience from both academia and government, Drs Marles and Betz shared their insights into challenges and opportunities in the area of NHP analysis ad product quality.

More information on the conference and society can be found at www.nhprs.ca

Dr John Thor Arnason, Michael Smith and Dr Julia Solnier

Dr Julia Solnier, Dr Paul Spagnuolo, and Dr John Thor Arnason

Michael Smith and Dr Julia Solnier