Berberine vs. Berberine HCl: Understanding the Differences and Benefits

Berberine is a compound found in several plants, including the Berberis species, and has been used for centuries in traditional Chinese and Ayurvedic medicine. Known for its bright yellow color and potent health benefits, berberine has gained popularity in the Western world for its ability to support metabolic health, cardiovascular function, and more.

When exploring supplements, you might encounter both "berberine" and "berberine HCl" on labels, leading to confusion about their differences and which form is best for your needs. This article explains the differences between berberine and berberine HCl, highlighting their distinctions, benefits, and how to choose the right one for you.

Oregon Grape Root (Mahonia aquifolium) contains the naturally occuring alkaloid berberine.

What is Berberine?

Berberine is an alkaloid, a class of naturally occurring compounds often noted for their pharmacological effects. It is extracted from the roots, bark, and stems of various plants, including plants of the Berberis species like goldenseal (Hydrastis canadensis), Oregon grape (Mahonia aquifolium), and barberry(Berberis vulgaris) Berberine is traditionally used to treat gastrointestinal issues, infections, and more recently, for its potential to regulate blood sugar levels, support weight management, and improve heart health.

What is Berberine HCl?

Berberine HCl (hydrochloride) is the hydrochloride salt form of berberine. This form is created by combining berberine with hydrochloric acid to enhance its solubility and ability to be absorbed in the body. The addition of hydrochloric acid doesn't significantly alter the properties of berberine but makes it easier for the body to absorb and utilize. Most berberine supplements in the market are in the form of berberine HCl due to its improved absorption rate.

Comparing Berberine and Berberine HCl

  • Bioavailability: The primary difference between berberine and berberine HCl lies in their bioavailability. Berberine HCl is more readily absorbed by the body, making it potentially more effective, especially for metabolic and cardiovascular health support.

  • Usage and Benefits: Both forms of berberine offer similar health benefits, including supporting blood sugar regulation, cardiovascular health, and anti-inflammatory and antimicrobial properties. The choice between the two often comes down to the bioavailability and how well your body can utilize the compound.

  • Side Effects and Tolerance: Berberine and berberine HCl can cause some gastrointestinal discomfort, especially at higher doses. Due to its higher absorption, berberine HCl might lead to more pronounced effects, both in terms of benefits and potential side effects.

How to Choose Between Berberine and Berberine HCl

When deciding between berberine and berberine HCl, consider the following factors:

  • Health Goals: If you're looking for maximum efficacy, particularly for metabolic and cardiovascular support, berberine HCl might be the better choice due to its enhanced bioavailability.

  • Digestive Sensitivity: If you have a sensitive stomach, start with a lower dose to assess tolerance, regardless of the form you choose.

  • Quality and Purity: Look for supplements from reputable brands that offer transparency about sourcing, manufacturing practices, and third-party testing to ensure product purity and potency. If you’re curious about exploring a trusted source for high-quality organic herbs, I often source herbs from Starwest Botanicals and Mountain Rose Herbs.

  • Sensitivities to Additives: When selecting a berberine or berberine HCl supplement, it's important to be aware of potential sensitivities to additives. Some supplements may contain fillers, binders, or other additives that could cause adverse reactions in sensitive individuals. Opting for high-quality, pure formulations with minimal additives can help mitigate this risk and ensure better tolerance.

Whole Herb Supplements vs. Single Ingredient Extracts

When considering the use of berberine, individuals also have the option to take it as a single constituent supplement or opt for the whole herbs (Hydrastis canadensis, Mahonia aquifolium, Berberis vulgaris) that naturally contain the berberine compound. This choice presents an interesting consideration between whole herb supplements and single-ingredient extracts.

Whole Herb Supplements: These supplements contain the entire range of compounds found in the plant, not just berberine. The philosophy behind whole herb supplements is based on the belief that all the components in a plant work together synergistically, potentially offering a more balanced effect. For example, using an Oregon Grape Root tincture would provide not only berberine but also other alkaloids and compounds contained in the plant. This holistic approach is thought to mirror the traditional use of these plants in herbal medicine, where the whole plant's properties are utilized for healing.

Single Ingredient Extracts: In contrast, single ingredient extracts, such as berberine supplements, focus on isolating and delivering a high concentration of berberine alone. This allows for precise dosage and targeted therapy, particularly for conditions where berberine's specific effects are desired. For those interested in the specific benefits of berberine, such as its impact on blood sugar levels or cholesterol, a single ingredient extract might be preferred for its potency and direct action. Below are some trusted examples that I recommend to my patients.

Choosing between whole herb supplements and single ingredient extracts depends on individual preferences, the desired therapeutic outcome, and considerations of how the body responds to herbal complexes versus single compounds. Some may prefer the targeted approach of single ingredient extracts, while others might lean towards the holistic benefits of whole herb supplements, valuing the natural balance and synergy of compounds found in the entire plant.

Is Berberine Effective?

Berberine has been a subject of interest in the health and wellness community for its potential therapeutic benefits. Its effectiveness spans across various conditions, making it a versatile addition to the natural health toolkit. Let's look at the areas where berberine shows promising results.

Berberine for Canker Sores

Anyone who's experienced the discomfort of canker sores knows how welcome an effective remedy would be. Berberine steps into this arena with a gel formulation that has been observed to alleviate the pain, redness, and size of these pesky oral nuisances. Its application not only soothes but also accelerates the healing process, offering a natural solution to those seeking relief.

Research Highlights: Some clinical research shows that applying a gel containing berberine 5 mg/gram four times daily for 5 days can reduce pain by 26% and ulcer size by 30% when compared with placebo in patients with minor recurrent canker sores. (7)

Berberine for Diabetes Management

Diabetes management is a complex journey involving blood sugar regulation. Berberine introduces a natural approach, with oral intake showing a potential to modestly lower blood sugar levels in diabetic individuals. This suggests that berberine could be a helpful supplement in the treatment of diabetes, alongside conventional treatments.

Research Highlights: Berberine moderately reduces blood sugar levels in people with type 2 diabetes, especially when used with other common diabetes medicines. Some studies have found that taking berberine, about 500 mg two or three times a day for a few months, can help lower blood sugar levels, diabetes associated blood markers, and might work as well as some diabetes drugs like metformin or rosiglitazone (12). Another large meta-analysis showed that when people added berberine to their usual diabetes drugs and made healthy lifestyle changes, they saw even better improvements in their blood sugar levels. (9)

Cholesterol and Blood Pressure

Hyperlipidemia, characterized by elevated levels of cholesterol and other lipids, poses significant health risks. Berberine's ability to potentially lower total cholesterol, LDL ("bad") cholesterol, and triglycerides highlights its role in promoting heart health. Moreover, when used alongside the blood pressure medication amlodipine, berberine may enhance blood pressure reduction, offering a complementary strategy for managing hypertension.

Research Highlights: Clinical research shows that taking berberine orally, alone or in combination with other ingredients, reduces total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides, and increases high-density lipoprotein (HDL) cholesterol (8)(4). In individuals with hypertension a meta-analysis shows that taking berberine 0.9 grams daily in combination with amlodipine for 2 months reduces systolic blood pressure by 5 mmHg and diastolic blood pressure by 2 mmHg when compared with amlodipine alone (9).

Addressing PCOS Symptoms

Polycystic ovary syndrome (PCOS) affects many aspects of health, including hormonal balance and metabolic function. Berberine's impact on PCOS is multifaceted: it may improve cholesterol and triglyceride levels, reduce testosterone levels, and even influence body composition, as indicated by a lower waist-to-hip ratio. These benefits suggest that berberine could be a valuable component of a holistic PCOS management plan.

Research Highlights: Berberine may improve some metabolic characteristics in women with PCOS and insulin resistance. Clinical research in patients with PCOS and insulin resistance shows that taking berberine 500-550 mg 2-3 times daily for 3 to 6 months reduces fasting plasma glucose, markers of insulin resistance, total cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, testosterone levels, body mass index, waist-to-hip ratio, acne severity, and markers of inflammation when compared with placebo or baseline. Berberine also seems to increase high-density lipoprotein (HDL) cholesterol and sex hormone binding globulin (SHBG) levels (11)( 2).

How to Take Berberine Safely

While berberine presents a beacon of hope for various health conditions, understanding its safety profile is crucial for informed usage. Let's explore the safety considerations, common side effects, and special precautions associated with berberine to ensure it is taken safely and effectively.

General Safety and Side Effects

For most adults, taking berberine orally is considered safe within the recommended dosages. It has been used without significant issues in doses of up to 1.5 grams daily for up to six months. However, like many supplements, it may come with some digestive side effects, including diarrhea, constipation, gas, and upset stomach. These are common and often mild, but they're important to keep in mind, especially for those with sensitive digestive systems.

When it comes to topical application, berberine is also considered possibly safe for short-term use in adults. This provides a comforting option for those looking to use berberine externally, such as for canker sores.

DOSING SUMMARY:

Dosing: Orally- Berberine has been used safely in doses up to 1.5 grams daily for 6 months. Topically - Berberine ointment has been applied with apparent safety for up to 20 days.

Possible Side Effects: Diarrhea, constipation, gas, and upset stomach.

Special Precautions & Warnings

While berberine offers many potential benefits, certain groups should exercise caution or avoid it altogether:

  • Pregnancy: Berberine is likely unsafe during pregnancy. It has the ability to cross the placenta, posing a risk to the developing fetus. There have been instances where exposure to berberine led to kernicterus, a serious form of brain damage, in newborns.

  • Breastfeeding: Nursing mothers should also steer clear of berberine. It can pass into breast milk and potentially harm the nursing infant.

  • Newborns and Children: Berberine may interfere with the liver's ability to process bilirubin, a byproduct of red blood cell breakdown. This is especially concerning in infants with high bilirubin levels, where it could exacerbate the risk of brain damage. Safety has not been established with children.

Understanding Berberine's Interactions with Medications and Supplements

Berberine has been shown to have several interactions with various medications and supplements. It's crucial to be aware of these interactions to avoid adverse effects and ensure the safe use of berberine.

Major Interactions to Note

  • Cyclosporine: Berberine can slow down the breakdown of cyclosporine in the body, potentially amplifying its effects and side effects. It's advised not to combine these two.

Moderate Interactions

  • Medications Metabolized by the Liver: Berberine may alter the speed at which the liver processes certain drugs, including those metabolized by Cytochrome P450 enzymes (CYP2C9, CYP2D6, CYP3A4). This could modify the effectiveness and side effects of these medications.

  • Diabetes Medications: Since berberine can lower blood sugar, combining it with antidiabetic drugs might lead to hypoglycemia. Close monitoring of blood sugar levels is essential.

  • Blood Pressure Medications: Berberine's potential to lower blood pressure could be compounded when taken with antihypertensive drugs, risking excessively low blood pressure.

  • Blood Clotting Medications: Some animal studies have found that berberine may slow blood clotting. This might increase the risk of bruising and bleeding when taken with anticoagulant or antiplatelet drugs.

  • Sedatives: Given berberine's sedative properties, using it alongside CNS depressants might result in excessive sleepiness or breathing difficulties.

Interactions with Supplements

  • Blood Pressure-Lowering Supplements: Theoretically, berberine might enhance the hypotensive effect of supplements like andrographis, L-arginine, and niacin, potentially causing blood pressure to drop too much.

  • Blood Sugar-Lowering Supplements: Similar to its interaction with diabetes medications, berberine combined with supplements like bitter melon or chromium could excessively lower blood sugar.

  • Blood Clotting Supplements: Berberine might slow down the process of blood clotting. Taking additional supplements that slow blood clotting, such as ginkgo or garlic, with berberine might heighten the risk of bleeding.

  • Sedative Supplements: Using berberine with supplements that have sedative effects, like melatonin or valerian, could lead to increased drowsiness or slowed breathing.

  • Probiotics: Berberine's antibacterial properties might affect probiotics, potentially diminishing their effectiveness.

Given these interactions, it's important for individuals considering berberine, especially those on medication or using other supplements, to consult with a healthcare provider. This ensures personalized advice and safe integration of berberine into your health regimen, taking into account its interactions with other substances.

Ethical Sourcing of Berberine

Berberine is naturally found in several plants. These plants have been used in traditional medicine across different cultures for centuries, highlighting berberine's long-standing therapeutic role. When choosing a berberine supplement, considering the source is important.

Ethnobotanical and Environmental Considerations

Ethnobotany is the study of how different cultures use plants for various purposes, such as medicine, food, clothing, and rituals. It explores the relationship between people and plants, uncovering traditional knowledge and practices that have been passed down through generations. This field helps us understand the cultural significance of plants and their role in traditional medicine, conservation, and sustainable use.

Because berberine is highly coveted for its therapeutic benefits, the increasing demand has raised environmental concerns, particularly regarding the sustainable harvesting of berberine and the conservation of these plants. Ethical sourcing and environmental stewardship are crucial to ensure that the benefits of berberine are available for future generations. As a Naturopathic doctor who readily uses and prescribes herbs, I always consider this aspect and urge my patients to do the same when it comes to selecting herbs for therapeutic use.

Berberine: Key Takeaways

Berberine stands out as a potent and therapeutic herb, celebrated for its wide array of health benefits. However, its power also demands a degree of mindfulness and respect as with taking any sort of medicine.

Like all herbs with significant medicinal properties, berberine interacts with the body in complex ways, capable of influencing many physiological processes and interacting with medications and supplements. This underscores the importance of using berberine with an informed mindset, recognizing its potential while also acknowledging the need for obtaining appropriate and reliable information to harness its benefits safely and effectively.

Both berberine and berberine HCl offer significant health benefits, particularly for metabolic and cardiovascular health. The choice between the two primarily hinges on the issue of absorption, with berberine HCl generally being more easily absorbed by the body.

When selecting a supplement, consider your specific health needs, potential sensitivity, and the quality of the product. As with any supplement, it's wise to consult with a healthcare professional before adding berberine or berberine HCl to your regimen, especially if you have underlying health conditions or are taking medications.


Resources:

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  2. An Y, Sun Z, Zhang Y, Liu B, Guan Y, Lu M. The use of berberine for women with polycystic ovary syndrome undergoing IVF treatment. Clin Endocrinol (Oxf). 2014 Mar;80(3):425-31. doi: 10.1111/cen.12294. Epub 2013 Aug 9. PMID: 23869585.

  3. Berberine. Altern Med Rev. 2000 Apr;5(2):175-7. PMID: 10767672.

  4. Blais JE, Huang X, Zhao JV. Overall and Sex-Specific Effect of Berberine for the Treatment of Dyslipidemia in Adults: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials. Drugs. 2023 Apr;83(5):403-427. doi: 10.1007/s40265-023-01841-4. Epub 2023 Mar 21. PMID: 36941490.

  5. Imanshahidi M, Hosseinzadeh H. Pharmacological and therapeutic effects of Berberis vulgaris and its active constituent, berberine. Phytother Res. 2008 Aug;22(8):999-1012. doi: 10.1002/ptr.2399. PMID: 18618524.

  6. Janeczek M, Moy L, Lake EP, Swan J. Review of the Efficacy and Safety of Topical Mahonia aquifolium for the Treatment of Psoriasis and Atopic Dermatitis. J Clin Aesthet Dermatol. 2018 Dec;11(12):42-47. Epub 2018 Dec 1. PMID: 30666279; PMCID: PMC6334833.

  7. Jiang XW, Zhang Y, Zhu YL, Zhang H, Lu K, Li FF, Peng HY. Effects of berberine gelatin on recurrent aphthous stomatitis: a randomized, placebo-controlled, double-blind trial in a Chinese cohort. Oral Surg Oral Med Oral Pathol Oral Radiol. 2013 Feb;115(2):212-7. doi: 10.1016/j.oooo.2012.09.009. Epub 2012 Dec 12. PMID: 23246229.

  8. Kong W, Wei J, Abidi P, Lin M, Inaba S, Li C, Wang Y, Wang Z, Si S, Pan H, Wang S, Wu J, Wang Y, Li Z, Liu J, Jiang JD. Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins. Nat Med. 2004 Dec;10(12):1344-51. doi: 10.1038/nm1135. Epub 2004 Nov 7. PMID: 15531889.

  9. Lan J, Zhao Y, Dong F, Yan Z, Zheng W, Fan J, Sun G. Meta-analysis of the effect and safety of berberine in the treatment of type 2 diabetes mellitus, hyperlipemia and hypertension. J Ethnopharmacol. 2015 Feb 23;161:69-81. doi: 10.1016/j.jep.2014.09.049. Epub 2014 Dec 10. PMID: 25498346 (listed twice, same details).

  10. Rabbani GH, Butler T, Knight J, Sanyal SC, Alam K. Randomized controlled trial of berberine sulfate therapy for diarrhea due to enterotoxigenic Escherichia coli and Vibrio cholerae. J Infect Dis. 1987 May;155(5):979-84. doi: 10.1093/infdis/155.5.979. PMID: 3549923.

  11. Wei W, Zhao H, Wang A, Sui M, Liang K, Deng H, Ma Y, Zhang Y, Zhang H, Guan Y. A clinical study on the short-term effect of berberine in comparison to metformin on the metabolic characteristics of women with polycystic ovary syndrome. Eur J Endocrinol. 2012 Jan;166(1):99-105. doi: 10.1530/EJE-11-0616. Epub 2011 Oct 21. PMID: 22019891.

  12. Zhang Y, Li X, Zou D, Liu W, Yang J, Zhu N, Huo L, Wang M, Hong J, Wu P, Ren G, Ning G. Treatment of type 2 diabetes and dyslipidemia with the natural plant alkaloid berberine. J Clin Endocrinol Metab. 2008 Jul;93(7):2559-65. doi: 10.1210/jc.2007-2404. Epub 2008 Apr 8. PMID: 18397984.

  13. Zeng XH, Zeng XJ, Li YY. Efficacy and safety of berberine for congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol. 2003 Jul 15;92(2):173-6. doi: 10.1016/s0002-9149(03)00533-2. PMID: 12860219.

Medical Disclaimer: The content provided on this blog, including text, graphics, images, and other material, is for informational purposes only and is not intended to be a substitute for professional medical advice, diagnosis, or treatment. The information on this blog is not intended to replace a one-on-one relationship with a qualified healthcare professional and is not intended as medical advice. Please consult your healthcare provider before making any changes to your health regimen.

 

Are you interested in using herbal therapies to support your health? Let’s connect!

Dr. Linda Nykin, ND

Dr. Linda Nykin is a Naturopathic Doctor and Functional Medicine Practitioner specializes in helping women heal their metabolic health, gut health, hormone issues, and complex chronic diseases. She empowers individuals to become their own healers through education, coaching, and personalized wellness strategies that align with their unique life circumstances and health goals.

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