The Natural Health Products Regulations (NHPR) were developed in response to a demand from Canadians. They wanted access to high quality natural health products (NHPs) that were safe, effective and respected traditional forms of health and healing. Previously, the regulatory system focussed on conventional medicines and was not appropriate for NHPs. This changed in January 2004 when a specific regulatory approach for NHPs came into effect. The NHPR were developed following extensive national consultations hearing from Canadians and based on the recommendations of an Expert Advisory Committee.

The NHPR have been in place for over two decades and there have been many changes made to both how the NHPR are implemented and the regulatory environment in which they exist. The last five years have been particularly dynamic with many changes proposed and implemented. This article will provide an update on three key areas: Red Tape Reduction Initiative, Plain Language Labelling, and Cost Recovery.

Red Tape Reduction Initiative

Though based on an act of Parliament from 2015, the Red Tape Review was announced by the Secretary of the Treasure Board in July 2025. This cross federal government initiative “requires all departments to review their regulations and propose measures to eliminate burden, such as removing outdated rules, reducing duplication with provincial regulations, and streamlining processes”. Red Tape is defined as “unnecessary and overly complicated regulations” with this review intended to “support economic growth, improved efficiency, and make it easier for Canadians and businesses to interact with government services”.

In response, Health Canada and the Public Health Agency of Canada published a report presenting 42 initiatives either completed, almost completed or that should be completed in the next 2 years.

Regarding NHPs, Health Canada has committed to reducing regulatory burden by introducing a simpler registration process, and adopting a flexible, risk-based approach to monitoring. There is a plan to table amendments that support more flexible labelling requirements (see Plain Language Labelling below) and to move Health Canada oversight, when appropriate, from post market to premarket.

More information about the Health Canada/PHAC report can be found at: https://www.canada.ca/en/services/health/publications/health-system-services/report-red-tape-reduction.html

Plain Language Labelling (PLL)

Since their inception, the NHPR contained provisions required for NHP labels developed through extensive consultations. However, the federal government, launched three years of closed-door consultations with stakeholders on labelling. This culminated in 2021, when Health Canada published a public consultation initiative to include NHPs within a broader Over-the-Counter medicine labelling initiative called Plain Language Labelling. Health Canada’s stated aim for this process was to “address poor communication of key information on health products label that can lead to in correct purchases and preventable harm”. These proposed labelling changes fell within four basic areas:

• inclusion of a mandatory table format for product information
• clarifying existing allergen labelling requirements to include priority food allergens
• clearly and prominently displayed label text, and
• allowing for civic addresses to be replaced with websites for company contact information.

So, the Plain Language Labelling initiative, did not focus on simplifying the language of labels.

Major concerns were raised by many stakeholders not only about the effectiveness of these changes in reducing risk and supporting informed choice but also the decision to prioritise these changes over other more serious issues and the feasibility of their implementation. In addition, concerns were raised about how seriously Health Canada took the feedback provided over the previous years of closed-door and open consultation.

Despite these stakeholder concerns, Health Canada moved ahead with a slightly modified approach which was passed into law in July 2022. Recognising that these new regulations would require extensive changes to NHP labels, Health Canada required implementation of the changes for new products to be done within 3 years and, for existing NHPs, required label changes to be made within 6 years.

A more detailed description can be found in a previous ISURA articles: Improved Labelling for Natural Health Products – The Final Regulations.

While these new labelling regulations have not changed, in the face of significant lobbying and push back from stakeholders notably the NHP industry, Health Canada modified the implantation timeline with a temporary compliance exemption. This allows companies to follow the previous labelling requirements for NHPs licensed between June 21, 2025 and June 21 2028. While this compliance exemption is in place, Health Canada has committed to work with industry as part of the Red Tape Reduction Initiative to address issues and to introduce “flexible labelling requirements through targeted regulatory amendments”. This will be part of the Reducing Red Tape initiative identified above.

Cost Recovery

 Cost recovery is a mechanism by which a regulator can charge fees to either completely or partially cover their costs for operating a regulatory framework. Currently a cost recovery system exists in Canada for all approved medicines with the exception of NHPs. Food regulatory programs are also not subject to cost recovery. In May 2023, Health Canada posted a proposed approached with suggested fees. This proposed framework would apply to NHP product licence applications, NHP site licence applications, and post-market activities captured under a fee called Right to Sell (RTS). These fees would apply to any organisation with a Health Canada regulatory requirement such as sponsors, manufacturers, distributors and importers of NHPs. The framework also included a mitigation for small businesses, performance standards for Health Canada with penalties if the standards are not met, and the creation of a new category: Class III novel applications not defined in regulation or guidance documents. The initial, proposed implementation date for the framework was April 1, 2025, with an estimated annual cost to industry of $100.8M.

More details together with a comparison with key international jurisdictions can be found in a previous ISURA article: Comparing NHP Regulations from Canada and Australia.

In April 2024, in response to consultation and following focussed workshops with key stakeholder groups, Health Canada posted an updated approach for the Cost Recovery initiative with a modified fee scale. The basic approach was to focus on recovering costs for existing program activities and postponing system improvements such as the use of IT systems, quality review of submissions and audit functions; strengthening the review of efficacy date for products making claims for strengthening diseases; strengthening oversight of online advertising; and increasing capacity for processing and education. It is estimated that this would reduce annual costs from $100.8M to $51.1M. None of the proposed system improvements are predicted by government to have an impact on review times, costs, or other metrics of improvement. In addition, pertinent details were lacking including how references to clinical terms would be defined, how strengthened compliance would be administered, and challenges with past education programs would be addressed.

This modified approach would:

• Lower the fee setting ratio, or the portion of costs included in the fee charged to industry versus that paid by taxpayers, for the first 4 years:
• Phase in fees over a 7-year period based on a coming into force on December 1, 2025;
• Remove the proposed Class III- Novel category; and
• Reduce the number of fee categories associated with annual site licensing from 5 to 3.

The current cost recovery document can be found at:

https://www.canada.ca/en/health-canada/services/drugs-health-products/natural-non-prescription/regulation/cost-recovery/revisions-proposed-fees.html

Following the spring 2025 federal election, this initiative was paused but not officially abandoned. A proposed start date of December 1, 2025 was the last implementation date posted publicly. However, as of November 2025, this implementation date has been delayed until an unspecified future date while a reassessment is completed.

Final Thoughts

When the Natural Health Products Regulations were developed and implemented in the early 2000s they were rather unique with few international examples from which to learn. Much has changed in the past couple of decades and, in hindsight, some things could have been done differently. At their core the NHPR are solid. Many of the problems facing the public today are related to the government’s interpretation of the wording of the regulations and its implementation of them over the past decade than the regulations themselves.

Under the Red Tape Reduction Initiative, the opportunity exists to again make the Canadian approach a global gold standard. This could include:

• Using IT and online functions to replace the current complicated people and paper heavy process.
• Leveraging existing initiatives to streamline the number of inspections of NHP manufacturing sites.
• Developing a public system, much like food nutrition programs, for communicating both the benefits and appropriate use of NHPs.
• Working with international partners to reflect a global marketplace.

The possible changes outlined in the red tape reduction report are only in play due to the strong advocacy of the Canadian Health Food Association and from NHP companies. In addition, recent changes in government priorities have left a number of loose ends, notably around cost recovery and the new labelling requirements which are now in law. While the Red Tape Reduction Initiative provides an opportunity to effectively resolve these loose ends, the NHP community must remain vigilant to ensure that government remains committed to tangible positive improvements in the sector and for Canadians.

About the author:

Michael Smith trained as a pharmacist and as a naturopathic doctor. He is recognized internationally as an expert in natural health products and complementary & alternative medicine. For more than 10 years, he worked in senior regulatory positions at the then Natural Health Products Directorate, Health Canada, and the Therapeutic Goods Administration in Australia. In addition to his international work as a consultant, he is an Adjunct Professor at the National Center for Natural Products Research at the University of Mississippi, USA and an Adjunct Associate Professor at the National Centre for Naturopathic Medicine at Southern Cross University, Australia. He is a member of ISURA’s Scientific Advisory Committee.

Download a PDF version of this article: Here

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