Safety Evaluation and Concerns of Natural Products in Traditional Medicine

1.0 Introduction

Traditional medicine systems have served as the cornerstone of healthcare for centuries in many cultures, particularly across Asia, Africa, and South America. These systems rely heavily on natural products—plants, minerals, and animal-derived substances—for the treatment and prevention of disease (World Health Organization, 2013). In recent decades, there has been a notable global resurgence in the use of traditional remedies, fueled by cultural continuity, dissatisfaction with conventional therapies, and a growing preference for holistic and “natural” approaches to health (Bent, 2008).

The widespread perception that natural products are inherently safe because they are “natural” has contributed to their increasing use in both self-medication and integrative clinical practice (Ernst, 2004). However, this assumption often fails to account for the complex chemical profiles of natural remedies, the variability in preparation, and the lack of standardized dosing, which may lead to serious adverse effects. Indeed, several high-profile cases of toxicity, contamination, and herb-drug interactions have shifted attention toward the importance of rigorous safety evaluations (Posadzki et al., 2013).

Emerging evidence underscores the therapeutic benefits of plant-based compounds, including their antioxidative and anti-inflammatory properties. For instance, Adegbesan et al. (2021) demonstrated that ORAL CELLGEVITY® improves antioxidant parameters and mitigates oxidative damage in diabetic models. Similar antioxidant and anti-proliferative effects have been observed in studies involving compounds such as diphenyl diselenide (Edema et al., 2023) and protocatechuic acid (Onah et al., 2024), which have shown protective roles against chemically induced carcinogenesis.

Natural products used in traditional medicine include a wide range of materials, such as herbs (e.g., Panax ginseng, Curcuma longa), resins (e.g., frankincense), animal-based substances (e.g., snake venom in TCM), and mineral derivatives (e.g., arsenic trioxide in Ayurvedic Rasashastra). Many of these agents contain pharmacologically active compounds that exert therapeutic effects but may also induce toxicity, especially in sensitive populations or under chronic exposure (Wachtel-Galor & Benzie, 2011). Recent studies have shown that water extracts from Momordica charantia significantly reduce oxidative and colonic inflammation, suggesting a protective role in gut health (Omiyale et al., 2024b).

Complementary and alternative medicine (CAM) practices often rely on these natural products in forms that bypass formal drug approval pathways. Unlike pharmaceutical drugs, which undergo rigorous safety, efficacy, and quality control testing, many natural products are sold as dietary supplements, making them subject to significantly less regulatory scrutiny (Marcus & Grollman, 2002). This discrepancy contributes to a knowledge gap in terms of safety profiles, contraindications, and interaction potential.

Furthermore, traditional remedies may be prepared using varied extraction methods (e.g., decoctions, tinctures, powders) that influence their chemical composition and bioavailability (Ekor, 2014). These inconsistencies complicate the identification of active principles and the prediction of pharmacokinetic behavior. Even within a single plant species, factors such as geographic origin, harvest season, soil composition, and post-harvest processing can alter chemical profiles dramatically (Liu et al., 2021).

For example, recent advances have identified the bioenhancing properties of novel protein-based delivery systems using natural compounds in cancer treatment (Ogunjobi et al., 2025). This review aims to provide a comprehensive and evidence-based analysis of the safety concerns surrounding natural products commonly used in traditional medicine. Key topics include intrinsic toxicity, contamination and adulteration, quality control deficiencies, herb-drug interactions, and misuse stemming from misinformation. It also explores the methodologies used in modern pharmacovigilance and toxicology to assess and manage risks associated with these products.

Given the increasing integration of traditional and natural remedies into global health systems, a thorough understanding of these safety issues is essential for healthcare providers, researchers, and consumers alike. Responsible use, combined with scientific evaluation and regulatory oversight, is critical to maximizing the therapeutic potential of natural products while minimizing their risks. Some studies have even reported that combinations of antioxidants found in traditional preparations may prevent atherogenic dyslipidemia and enhance glycemic control in metabolic disorders (Ogunlabi et al., 2020; Omiyale et al., 2024a).

Figure 1. Mechanistic Overview of Safety Concerns Associated with Natural Products: This schematic illustrates the major safety challenges linked to natural products commonly used in traditional medicine and dietary supplements. Central to the diagram is a representation of natural product formulations surrounded by five key hazard categories: (1) Intrinsic toxicity, due to complex chemical compositions and the presence of inherently toxic phytochemicals (e.g., pyrrolizidine alkaloids in comfrey, ephedrine in ephedra); (2) Herb–drug interactions, which may alter pharmacokinetics or pharmacodynamics of concurrent medications, such as increased bleeding risk when combined with anticoagulants; (3) Misuse, including unsupervised self-medication, overdosing, and substitution for prescribed therapies, often driven by misinformation; (4) Contamination and adulteration, involving exposure to heavy metals, microbial toxins, or undeclared synthetic drugs like sildenafil or corticosteroids; and (5) Lack of standardization, contributing to unpredictable dosing and inconsistent therapeutic effects. These factors collectively increase the risk of organ toxicity, poor therapeutic outcomes, and adverse interactions, underscoring the need for rigorous safety evaluation, regulatory oversight, and informed clinical use.

The resurgence of interest in traditional medicine and natural products globally is driven by a combination of cultural beliefs, accessibility, and skepticism toward synthetic pharmaceuticals. While natural products offer significant therapeutic potential, their safety remains a pressing concern, particularly when used in unregulated or unsupervised contexts. Traditional formulations often comprise multiple bioactive compounds with poorly understood pharmacodynamics and pharmacokinetics, posing unique safety challenges. This review comprehensively addresses the key concerns related to the safety of natural products and suggests methods for rigorous scientific evaluation and risk mitigation.

2.0 Intrinsic Toxicity, Chemical Complexity, and Toxicological Concerns of Natural Products

 Natural products, widely regarded as reservoirs of therapeutic agents, are inherently complex and biologically potent. Unlike synthetic pharmaceuticals which are often composed of a single active ingredient, natural remedies typically consist of mixtures containing dozens to hundreds of phytochemicals. These constituents can interact synergistically, additively, or antagonistically, thereby complicating both efficacy and safety assessments. Importantly, the therapeutic effect and toxicity of many plant-based treatments often stem from the same bioactive compounds, emphasizing the necessity for rigorous toxicological scrutiny.

2.1 Chemical Complexity and Dual Bioactivity

The multi-component nature of herbal preparations presents a significant challenge in toxicological profiling. The same compound may mediate both beneficial and harmful effects depending on the dosage, route of administration, bioavailability, individual metabolic variation, and co-administration with other agents. This dual-edged nature necessitates careful standardization and dosing.

2.2 Case Studies of Toxic Natural Products

A variety of traditional remedies, despite their long-standing use, have been implicated in serious toxicological outcomes:

• Comfrey (Symphytum spp.) Comfrey contains pyrrolizidine alkaloids (PAs), which are hepatotoxic and genotoxic. Chronic use has been linked to hepatic veno-occlusive disease, liver fibrosis, and hepatic failure. The FDA has warned against internal use due to these risks (Edgar et al., 2011).
• Ephedra (Ephedra sinica) Rich in ephedrine-type alkaloids, Ephedra exhibits potent sympathomimetic effects. It has been associated with hypertension, myocardial infarction, stroke, and seizures, prompting the U.S. FDA to ban its inclusion in dietary supplements in 2004 (Haller & Benowitz, 2000).
• Aconitum spp. (e.g., Aconite) Used in Traditional Chinese Medicine for analgesia and inflammation, aconitine and related alkaloids in these plants are potent neurotoxins and cardiotoxins. They can induce fatal arrhythmias, convulsions, and paralysis if improperly processed or overdosed (Chan, 2002).
• Gossypol; A polyphenolic aldehyde extracted from unrefined cottonseed oil, historically explored as a male contraceptive. Chronic ingestion can result in hypokalemia, infertility, and hepatotoxicity (Coutinho, 2002).
• Germander (Teucrium chamaedrys) Formerly promoted for weight loss and gastrointestinal ailments, Germander contains furan–containing diterpenoids that are hepatotoxic, leading to acute liver failure and subsequent regulatory bans (Larrey et al., 1992).
• Kava (Piper methysticum) Commonly used for anxiety and sleep disorders, Kava has been linked to idiosyncratic hepatotoxicity, possibly due to glutathione depletion and cytochrome P450 enzyme interference. Cases of severe liver damage led to market restrictions in several countries (Teschke & Lebot, 2011).
• Aristolochia spp. (Aristolochic Acids) Aristolochic acids are potent nephrotoxins and carcinogens, implicated in aristolochic acid nephropathy (AAN) and upper urinary tract cancers. Their irreversible renal and DNA-damaging effects have led to widespread bans (Debelle et al., 2008).
• Camphor; Traditionally used topically or internally for colds and inflammation, even small ingested doses of camphor can cause seizures, respiratory depression, and neurological toxicity, especially in children (Love et al., 2004).

3.0 Extrinsic Contamination and Adulteration of Natural Products

In addition to intrinsic toxicity, the safety profile of natural products is often compromised by extrinsic factors during various stages of their lifecycle — from cultivation and harvesting to processing, packaging, and marketing. These risks arise from environmental contamination, poor manufacturing practices, and intentional adulteration. Such issues pose serious threats to consumer health and undermine the credibility of natural product-based therapeutics. Major categories of extrinsic hazards include:

1. Heavy Metal Contamination

Heavy metals such as lead (Pb), mercury (Hg), cadmium (Cd), and arsenic (As) are frequently detected in traditional medicines, especially in certain Ayurvedic, Siddha, and Unani formulations. These contaminants may arise from:

• The intentional inclusion of metal-based preparations (e.g., bhasmas),
• Contaminated soil or irrigation water,
• Unsanitary storage containers and utensils during preparation.

A landmark study found that 20% of Ayurvedic products purchased online contained heavy metals exceeding safety thresholds. Chronic exposure to these metals is associated with neurotoxicity, nephrotoxicity, hematologic disorders, and carcinogenesis (Saper et al., 2004). In children, even low-level lead exposure can impair cognitive development.

2. Microbial and Fungal Contamination

Poor hygienic conditions during post-harvest handling, storage, or packaging can lead to microbial contamination. Fungi such as Aspergillus flavus and Aspergillus parasiticus thrive under warm and humid conditions and produce aflatoxins, among the most potent naturally occurring hepatocarcinogens. Chronic aflatoxin B₁ exposure has been linked to liver cancer, particularly in regions with high hepatitis B prevalence, due to synergistic effects.

Additionally, bacterial contamination (e.g., Salmonella spp., E. coli, Staphylococcus aureus) in powdered herbal supplements poses a risk of gastrointestinal infections and systemic illness, especially in immunocompromised individuals.

3. Synthetic Adulterants in Herbal Supplements

Adulteration of natural products with undeclared pharmaceutical ingredients is an increasingly reported global issue. Some products marketed for sexual enhancement, weight loss, or pain relief have been found to contain:

• Corticosteroids (e.g., dexamethasone)
• Phosphodiesterase-5 (PDE5) inhibitors (e.g., sildenafil)
• Anorectics (e.g., sibutramine)
• Nonsteroidal anti-inflammatory drugs (NSAIDs)

These adulterants are often added to enhance efficacy deceptively but can cause severe adverse effects including hypertension, stroke, cardiac events, liver damage, and drug-drug interactions. Regulatory agencies such as the U.S. FDA frequently publish warnings and recalls related to such contamination.

4. Misidentification and Substitution of Plant Species

Botanical misidentification—either accidental or due to deliberate economic motives—can result in the inclusion of toxic plant species or incorrect plant parts. A tragic example involves the substitution of Stephania tetrandra with Aristolochia fangchi in a weight-loss preparation. The latter contains aristolochic acids, which are potent nephrotoxins and carcinogens, leading to aristolochic acid nephropathy (AAN) and upper urinary tract cancers in affected individuals (Debelle et al., 2008).

Such events underscore the critical need for botanical authentication using:

• Morphological analysis
• Phytochemical fingerprinting (e.g., HPLC, TLC)
• DNA barcoding, which offers precise species-level identification even in powdered or processed materials.

5. Lack of Standardization and Quality Control

Unlike synthetic pharmaceuticals, natural products often fall outside the scope of stringent regulatory oversight and standardized manufacturing protocols. This lack of harmonized quality assurance poses significant challenges for safety, efficacy, reproducibility, and consumer confidence. Natural product variability is influenced by numerous biological and technical factors that remain largely unregulated in many jurisdictions.

1. Batch-to-Batch Variability

One of the most critical issues in natural product use is inconsistency in active compound concentrations across different product batches. This variability arises from several factors:

• Seasonal variation: Phytochemical content can change depending on the plant’s growth stage, time of harvest, and local climate.
• Geographical origin: Soil composition, altitude, and environmental stressors affect metabolite profiles.
• Post-harvest processing: Differences in drying techniques, storage conditions, and extraction methods further influence the final product.

This lack of consistency hampers dose standardization, making it difficult to achieve predictable pharmacokinetics and pharmacodynamics. As a result, therapeutic effects may vary widely, and toxicity risks may be inadvertently increased.

For example, ginsenosides in Panax ginseng can vary more than tenfold depending on cultivation and processing methods, significantly altering its pharmacological profile (Christensen, 2009).

2. Mislabeling, Adulteration, and Fraud

Numerous market analyses have revealed widespread issues with product mislabeling and intentional adulteration:

• Botanical products may be misidentified, either through human error or economic adulteration (i.e., substitution with cheaper species).
• DNA barcoding studies have shown that a significant number of commercial herbal products either contain undeclared ingredients or lack the labeled botanical species entirely (Newmaster et al., 2013).
• Products have also been found contaminated with allergens, toxins, heavy metals, or undeclared synthetic pharmaceuticals, posing serious public health threats.

Such fraudulent practices not only diminish efficacy but also endanger users through allergic reactions, drug interactions, or unexpected toxic effects.

Example: In a survey of herbal supplements in North America, nearly 60% contained substituted or contaminated ingredients, including potential allergens not listed on the label (Newmaster et al., 2013).

3. Lack of Pre-Market Safety and Efficacy Evaluation

In many countries, especially under dietary supplement regulations, natural products are not required to undergo pre-market safety or efficacy evaluations. For instance, in the United States, the Dietary Supplement Health and Education Act (DSHEA) of 1994 exempts supplements from rigorous FDA oversight:

• Manufacturers are not required to demonstrate safety or efficacy before marketing.
• Products can be sold until adverse events or misbranding issues are detected post-market.
• Only minimal oversight exists unless serious public health concerns emerge.

This regulatory gap allows under-tested or ineffective products to reach consumers, particularly in markets where natural products are assumed to be inherently safe due to their traditional use or natural origin.

4. Call for Harmonized Global Standards

Recognizing these risks, the World Health Organization (WHO) has urged the global adoption of standardized quality control measures. Key recommendations include:

• Good Agricultural and Collection Practices (GACP): Standardizing cultivation, harvesting, and post-harvest handling to ensure consistent raw materials.
• Good Manufacturing Practices (GMP): Enforcing hygienic, controlled, and validated production protocols to prevent contamination and variability.
• Validated analytical methods: Use of chromatography (HPLC, GC-MS), spectroscopy (NMR, IR), and molecular techniques (DNA barcoding) for accurate botanical identification and active ingredient quantification.

The WHO’s Traditional Medicine Strategy (2014–2023) and monographs provide a blueprint for national and international agencies to strengthen quality assurance systems for herbal medicines.

4.0. Herb–Drug Interactions

Herb-drug interactions are a major concern in integrative medicine, as natural products can modulate drug metabolism, absorption, and action through pharmacokinetic and pharmacodynamic mechanisms. These interactions may reduce drug efficacy, enhance toxicity, or precipitate adverse clinical outcomes.

1. Pharmacokinetic Interactions (Affecting ADME: Absorption, Distribution, Metabolism, Excretion)

• St. John’s Wort Induces CYP3A4, CYP2C9, CYP2C19, and P-gp, leading to enhanced metabolism and reduced plasma levels of many drugs, such as:
  • Cyclosporine → risk of graft rejection
  • Indinavir (HIV therapy) → viral breakthrough
  • Oral contraceptives → unintended pregnancy
  • Anticoagulants → thrombosis (Izzo & Ernst, 2009)
  • Grapefruit Juice Inhibits intestinal CYP3A4 and organic anion transporting polypeptides (OATPs), increasing systemic concentrations of drugs such as: Calcium channel blockers (e.g., felodipine), Statins (e.g., simvastatin), Immunosuppressants. This can lead to toxicity, including rhabdomyolysis, hypotension, and organ damage (Bailey et al., 2013).
• Ginseng (Panax spp.) Reports suggest it may antagonize warfarin, potentially via modulation of coagulation pathways or hepatic metabolism, although evidence is inconsistent.
• Cranberry (Vaccinium macrocarpon) Has been reported to potentiate warfarin activity in some studies via CYP2C9 inhibition, while other reports found no interaction. These inconsistencies highlight the need for individualized monitoring (Rindone & Murphy, 2006).

2. Pharmacodynamic Interactions (Affecting Receptor-Level or Physiologic Actions)

• Sedative Herbs (e.g., valerian, kava, passionflower): Potentiate the effects of central nervous system depressants, such as benzodiazepines and barbiturates, resulting in excessive sedation, respiratory depression, or prolonged anesthesia.
• Bleeding Risk Potentiators (e.g., garlic, ginkgo, ginseng): Can increase the risk of spontaneous or drug-induced bleeding when used with anticoagulants (e.g., warfarin, aspirin) by altering platelet aggregation, fibrinolysis, or vascular tone.

A. Misinformation and Improper Use

 Public perception often equates “natural” with “safe,” fostering widespread self-medication, over-reliance on anecdotal evidence, and the circulation of misleading health claims, especially online. This contributes to improper use and serious safety lapses:

1. Sources and Impacts of Misinformation

• Unregulated Online Platforms: Health blogs, forums, and social media channels often promote unverified therapeutic claims, including treatments for cancer, infections, and chronic diseases.
• Celebrity and influencer endorsements may lack scientific backing and contribute to viral misinformation.
• Language barriers and low health literacy further impair the ability to distinguish credible sources.

B. Common Misuse Patterns

• Overdosing: Many users assume higher doses of herbal remedies will increase efficacy, ignoring potential toxicity.
• Polyherbal Self-Medication: Concurrent use of multiple herbs and supplements increases the risk of interactions and unanticipated side effects.
• Discontinuation of Prescribed Therapies: Some patients replace evidence-based therapies with unproven natural alternatives, leading to disease progression (e.g., cancer, HIV, hypertension).

C. Regulatory and Educational Needs

• Labeling requirements should include potential interactions, side effects, and dosage instructions.
• Public education campaigns are essential to combat misinformation and promote evidence-based use.
• Healthcare providers must be trained to routinely ask about supplement use, document it, and provide informed counseling.

Example: A 2020 survey found that over 40% of patients using herbal supplements did not disclose their use to healthcare providers, increasing the likelihood of preventable adverse events and interactions (Walji et al., 2020).

5.0. Safety Evaluation Methods for Natural Products

Ensuring the safety of natural products requires a multifaceted evaluation approach that integrates preclinical and clinical methods, advanced analytical technologies, and post-market surveillance. Unlike conventional pharmaceuticals, many natural products lack comprehensive safety data due to regulatory exemptions or the historical assumption of safety. To mitigate risk and promote evidence-based use, robust methodologies must be applied across all stages of development and distribution.

A. In Vitro Toxicology

In vitro assays provide rapid, cost-effective means of evaluating the cytotoxicity, genotoxicity, and enzyme modulation potential of natural compounds:

• Cytotoxicity assays: e.g., MTT, LDH release, and Trypan Blue exclusion tests are used to evaluate cell viability.
• Genotoxicity tests: e.g., Ames test (mutagenicity), Comet assay (DNA strand breaks), and micronucleus tests.
• CYP enzyme modulation: High-throughput assays assess inhibition or induction of cytochrome P450 enzymes (especially CYP3A4, CYP2D6, CYP2C9), critical for predicting herb-drug interactions.

Example: Ethanolic extracts of Hypericum perforatum (St. John’s Wort) have demonstrated potent induction of CYP3A4 in hepatocyte cultures, mirroring in vivo drug interaction profiles.

B. In Vivo Animal Studies

Animal models remain the cornerstone of systemic toxicity assessment:

• Acute toxicity: Assessed through LD₅₀ determination to estimate the lethal dose in rodents.
• Subacute and chronic studies: Evaluate long-term effects, target organ toxicity, reproductive toxicity, and carcinogenicity.
• NOAEL (No Observed Adverse Effect Level) and LOAEL (Lowest Observed Adverse Effect Level) values guide safe dosing thresholds in humans.

However, ethical concerns and species-specific metabolic differences highlight the need to complement in vivo models with alternatives like organoids and 3D cultures.

C. Clinical Trials

Clinical studies are essential to establish tolerability, dosage range, safety margins, and adverse event frequency in humans. These trials must:

• Use standardized extracts to ensure reproducibility,
• Include diverse populations for assessing age-, sex-, and comorbidity-based effects,
• Monitor for drug–herb interactions.

Despite their necessity, such trials are often lacking due to limited commercial incentives, especially for non-patentable plant extracts.

Example: A randomized controlled trial on Kava extract in generalized anxiety disorder showed efficacy but raised safety concerns due to transaminitis, emphasizing the need for liver function monitoring (Sarris et al., 2013).

D. Pharmacovigilance

 Post-market surveillance is critical for identifying rare or delayed adverse effects not detected in pre-market testing:

• The WHO’s VigiBase and national systems (e.g., FDA’s MedWatch, EudraVigilance) collect spontaneous reports from healthcare providers and consumers.
• Adverse event databases support signal detection, regulatory decisions, and label updates.

However, underreporting remains a major challenge—especially in the case of over-the-counter supplements.

E. Advanced Analytical Tools 

High-resolution analytical platforms are essential for compound identification, quality assurance, and adulterant detection:

• HPLC, LC-MS, GC-MS: Used for quantitative and qualitative profiling of active ingredients, contaminants, and adulterants.
• NMR spectroscopy: Enables structural elucidation of unknown phytoconstituents.
• DNA barcoding: Provides species-level authentication, critical for identifying mislabeling or substitution in processed herbal products.

Example: DNA barcoding helped identify the presence of Aristolochia fangchi in mislabeled slimming supplements, linking it to aristolochic acid nephropathy outbreaks (Debelle et al., 2008).

6.0. Recommendations for Safe Use of Natural Products

To ensure the safe and effective use of natural products, a set of best-practice guidelines must be observed by consumers, healthcare providers, manufacturers, and regulators. These recommendations aim to balance therapeutic promise with safety assurance.

A. Disclose Supplement Use to Healthcare Providers

Patients should routinely inform physicians and pharmacists of all natural products they use, including teas, tinctures, capsules, and topicals. This information is crucial for:

• Avoiding drug interactions,
• Diagnosing unexplained symptoms,
• Guiding therapeutic decisions.

Survey Data: Over 40% of users of complementary therapies do not disclose supplement use to providers, increasing the risk of adverse outcomes (Walji et al., 2020).

B. Choose GMP-Certified Products from Reputable Manufacturers

Consumers should prioritize products that:

• Adhere to Good Manufacturing Practices (GMP),
• Provide standardized dosing and third-party testing,
• List full ingredient profiles, including excipients and extraction solvents.

Reputable companies often publish Certificates of Analysis (CoAs) verifying purity and potency.

C. Avoid Self-Treatment for Chronic or Serious Conditions

Herbal therapies should not be used as alternatives to proven treatments for chronic illnesses like cancer, diabetes, cardiovascular disease, or autoimmune conditions without clinical guidance. Doing so risks:

• Disease progression,
• Delayed diagnosis,
• Herb–drug interactions that alter treatment efficacy.

Case Example: Patients replacing antiretroviral therapy with herbal remedies have experienced viral rebound and disease progression (Mills et al., 2005).

D. Exercise Caution in Special Populations

Certain groups are more vulnerable to toxicity and interactions:

• Pregnant and lactating women: Potential teratogenic and hormonal effects.
• Children: Immature metabolic systems and dose sensitivity.
• Older adults: Polypharmacy, reduced hepatic/renal clearance.
• Patients on multiple medications: Increased risk of interactions.

E. Report Adverse Events

Consumers and professionals are encouraged to report adverse reactions to:

• National pharmacovigilance centers (e.g., MedWatch in the U.S.),
• Product manufacturers, and
• Online portals linked to WHO’s VigiBase.

This feedback loop enhances post-market surveillance, informs regulatory decisions, and protects future users.

7.0 Conclusion

While traditional medicine and natural products offer therapeutic value, their safety is often compromised by intrinsic toxicity, contamination, and lack of standardization. The belief that “natural” means “safe” overlooks the complex risks associated with these remedies. Strengthening scientific evaluation, regulatory oversight, and public awareness is essential. A balanced, evidence-based approach is needed to integrate natural products into modern healthcare without endangering patient safety.

References

1. Adegbesan, B. O., Ogunlabi, O. O., Olawale, O. O., Edema, A. A., & Onasanya, O. O. (2021). ORAL CELLGEVITY® improves antioxidant parameters and stalls damages in STZ-diabetic rat pancreas. FUW Trends in Science & Technology Journal, 6(1), 127–131. e-ISSN: 2408-5162; p-ISSN: 2048-5170
2. Bailey, D. G., Dresser, G. K., & Arnold, J. M. (2013). Grapefruit–medication interactions: Forbidden fruit or avoidable consequences? Canadian Medical Association Journal, 185(4), 309–316.
3. Bent, S. (2008). Herbal medicine in the United States: review of efficacy, safety, and regulation. Journal of General Internal Medicine, 23(6), 854–859.
4. Chan, T. Y. (2002). Aconite poisoning. Clinical Toxicology, 40(3), 291–296.
5. Coutinho, E. M. (2002). Gossypol: A contraceptive for men. Contraception, 65(4), 259–263.
6. Debelle, F. D., Vanherweghem, J. L., & Nortier, J. L. (2008). Aristolochic acid nephropathy: a worldwide problem. Kidney International, 74(2), 158–169.
7. Edema, A.A., Onah, C.N., Oloyede, A.A., & Adaramoye, O.A. (2023). Biochemical and Pharmacological Properties of Diphenyl Diselenide Against DMBA-Induced Mammary Tumorigenesis in Wistar Rats. International Journal of Toxicology, 42(1), 66.
8. Edgar, J. A., Colegate, S. M., & Boppré, M. (2011). Pyrrolizidine alkaloids in food: A spectrum of potential health consequences. Food Additives & Contaminants Part A, 28(3), 308–324.
9. Ekor, M. (2014). The growing use of herbal medicines: issues relating to adverse reactions and challenges in monitoring safety. Frontiers in Pharmacology, 4, 177.
10. Ernst, E. (2004). The risk–benefit profile of commonly used herbal therapies: Ginkgo, St. John’s Wort, Ginseng, Echinacea, Saw Palmetto, and Kava. Annals of Internal Medicine, 136(1), 42–53.
11. Haller, C. A., & Benowitz, N. L. (2000). Adverse cardiovascular events from dietary supplements containing ephedra alkaloids. New England Journal of Medicine, 343(25), 1833–1838.
12. IARC Working Group. (2012). Aflatoxins. In Chemical Agents and Related Occupations. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, 100F, 225–248.
13. Izzo, A. A., & Ernst, E. (2009). Interactions between herbal medicines and prescribed drugs: an updated systematic review. Drugs, 69(13), 1777–1798.
14. Larrey, D., Vial, T., Pauwels, A., et al. (1992). Hepatitis after germander (Teucrium chamaedrys) administration: Another instance of herbal medicine hepatotoxicity. Annals of Internal Medicine, 117(2), 129–132.
15. Liu, Y., Zhang, L., Song, H., & Guo, D. (2021). Metabolomics of traditional Chinese medicine: Current status and future perspectives. Chinese Medicine, 16(1), 1–17.
16. Love, J. N., Howell, J. M., & Litovitz, T. L. (2004). Camphor toxicity: Development of a triage algorithm. American Journal of Emergency Medicine, 22(7), 537–540.
17. Mahady, G. B. (2001). Ginkgo biloba for the prevention and treatment of cardiovascular disease: a review of the literature. Journal of Cardiovascular Nursing, 16(4), 21–32.
18. Marcus, D. M., & Grollman, A. P. (2002). Botanical medicines—the need for new regulations. New England Journal of Medicine, 347(25), 2073–2076.
19. Müller-Lissner, S. A. (2005). Safety aspects of laxatives. Drug Safety, 28(6), 531–544.
20. Ogunjobi, T. T., Nebolisa, N. M., Ajayi, R. O., Euba, M. I., Musa, A., Inusah, A.-H. S., Adedayo, F., Jamgbadi, O. F., Afuape, A. R., Edema, A. A., Echesi, S. A., Obasi, D. E., Abdul, S. O., & Adeyanju, S. A. (2025). Novel mechanism for protein delivery in breast cancer therapy: A public health perspective. European Journal of Sustainable Development Research, 9(2), em0283.
21. Ogunlabi, O. O., Adegbesan, B. O., Edema, A. A., Ademiluyi, S. T., & Ogundele, O. O. (2020). Treatment with Cellgevity® improves glycemic index and prevents atherogenic dyslipidemia in a type 2 diabetic rat model. LASU Journal of Health Sciences, 3(1).
22. Ogunlakin, A.D., Olanrewaju, A.A., Ojo, O.A., Akinwumi, I.A., Ambali, O.A., Otitoju, A., … & Sonibare, M.A. (2024). Synthesis, Antioxidant, and Antidiabetic Potentials of (Z)-((dimethylcarbamothioyl)thio)((1,1,1-trifluoro-4-oxo-4-phenylbut-2-en-2-yl)oxy) zinc hydrate. Comparative Clinical Pathology, 33(6), 949–959.
23. Omiyale, O., Awolade, R., Oyetade, O., Onuh, K., Chiemela, D., Odunlade, G., Shodipe, O., Demola, M., Agbanobi, M., Edema, A., & Ayeni, O. (2024a). Inflammation and Cancer: The Most Recent Findings. Journal of Health Science and Medical Research, 43(1), Article ID: 20241082.
24. Omiyale, O.C., Edu, Z., Nebolisa, N.M., Asebebe, A.B., Obasi, D.E., Edema, A.A., Abdul, S.O., Divine, U., Edem, P., & Ojo, B.O. (2024b). Water Extraction of Plant (Momordica charantia) Reduced Oxidative and Colonic Mucosal Inflammation in Colitic Male Balb/c Mice. Int. J. Adv. Biol. Biomed. Res. 2024, 12(3), 300-318
25. Onah, C.N., Edema, A.A., Adefisan, A.O., Oloyede, A.A., & Adaramoye, O. (2024). Protocatechuic Acid (PCA) Protects Against 7,12-Dimethylbenz(a)anthracene (DMBA)-Induced Mammary Gland Carcinogenesis in Wistar Rats via Antioxidative, Anti-inflammatory, Apoptotic, and Anti-proliferative Pathways. International Journal of Toxicology, 43(1), 112.
26. Posadzki, P., Watson, L. K., & Ernst, E. (2013). Adverse effects of herbal medicines: an overview of systematic reviews. Clinical Medicine, 13(1), 7–12.
27. Rindone, J. P., & Murphy, T. W. (2006). Does cranberry juice increase the INR? The Annals of Pharmacotherapy, 40(3), 520–523.
28. Sarris, J., et al. (2013). Kava in the treatment of generalized anxiety disorder: a double-blind randomized placebo-controlled study. Journal of Clinical Psychopharmacology, 33(5), 643–648.
29. Teschke, R., & Lebot, V. (2011). Proposal for a kava quality standardization code. Food and Chemical Toxicology, 49(10), 2503–2516.
30. S. FDA. (2021). Dietary Supplements. Available at: https://www.fda.gov/food/dietary-supplements
31. S. Food and Drug Administration. (2023). Tainted Products Marketed as Dietary Supplements. Available at: https://www.fda.gov/drugs/medication-health-fraud/tainted-products-marketed-dietary-supplements
32. Wachtel-Galor, S., & Benzie, I. F. (2011). Herbal Medicine: Biomolecular and Clinical Aspects. CRC Press.
33. Walji, R., Boon, H., Barnes, J., et al. (2020). Consumer use and disclosure of natural health products: a population survey. Canadian Journal of Public Health, 111(3), 402–410.
34. World Health Organization. (2013). WHO Guidelines on Good Agricultural and Collection Practices (GACP) for Medicinal Plants. WHO, Geneva.
35. World Health Organization. (2013). WHO Guidelines on Good Manufacturing Practices (GMP) for Herbal Medicines. WHO Press.
36. World Health Organization. (2014). WHO Traditional Medicine Strategy: 2014–2023. Geneva: WHO.