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    What is Berberine? Benefits, Dosage, and Risks

    What is Berberine? Benefits, Dosage, and Risks
    September 19, 2022 Vitality Pro

    What is Berberine? Benefits, Dosage, and Risks

    Berberine is an alkaloid found in certain berries, grapes, tree turmeric, and Goldenseal. Traditional Chinese Medicine has utilised this powerful plant compound for centuries. Today, ancient wisdom is increasingly being validated as researchers discover the key mechanisms driving this potent alkaloid’s ability to promote health and prevent age-related disease.

    What is Berberine?

    Berberine is an alkaloid that has a long history of use in Traditional Chinese Medicine. Most found in plants and fungi, alkaloids like berberine are nitrogen-based compounds known to have a wide range of physiological and psychoactive effects.

    Although it has origins in the far East, Western consumers have likely seen berberine on the shelves at local health and grocery stores– typically as 100% berberine, or as the supplement Golden Seal. Berberine can also be found in certain berries, grapes, and tree turmeric. Eating a diet rich in such plants and fungi may improve your exposure to this powerful alkaloid. However, a berberine supplement or extract is likely the best way to achieve therapeutic doses.

    According to a 2013 published in the academic journal China Life Sciences, berberine appears to have a “harmonious distribution” across key biological targets for the treatment of various chronic diseases. Researchers further note this makes the botanical compound an ideal therapeutic for conditions like type 2 diabetes, hyperlipidemia, heart disease, and inflammation.

    More recently, a 2021 paper published in the peer-reviewed journal Frontiers in Cellular and Infection Microbiology notes clinical trials show berberine “elicits clinical benefits at standard doses and has low toxicity“. Additional studies are needed, however, to better understand the health benefits and potential side effects of long-term use. For more information, see Potential Health Benefits of Berberine and Potential Health Risks and Side Effects below.

    Overview of Potential Benefits and Risks

    Berberine Benefits and Risks

    Disclaimer: Always consult your health care professional prior to making changes in your diet or exercise regimen, including whether to use supplements like berberine. Pregnant women, women who are nursing, and children must always consult a physician prior to taking supplements or medications.

    As a chemical class, alkaloids are known to have pronounced physiological and psychoactive effects. Some alkaloids create a stimulating effect, like those found in caffeine and nicotine. Alkaloids may also act as a sedative, like morphine. Still others may be psychotropic and produce hallucinogenic experiences, like lysergic acid diethylamide (LSD)– an alkaloid synthesized from the fungus, ergot.

    As with the alkaloids mentioned above, berberine appears to induce various physiological effects on the human body. One key difference: Berberine does not function as a stimulant, sedative, or psychoactive compound. In other words, a berberine supplement will not cause a perceivable feeling of some kind. Moreover, many centuries of use indicate berberine has immense potential therapeutic value with very little potential for harm.

    Below is a summary of both health benefits and potential risks and side effects of berberine.

    Overview of potential berberine health benefits:

    • Improved Gut Health & Digestion
    • Reduced Inflammation
    • Diabetes Treatment and Prevention
    • Reduced Insulin Resistance and Metabolic Disease Prevention
    • Obesity Prevention
    • Prevention of Liver Disease
    • Prevention of Cardiovascular Disease
    • Treats Diarrhea
    • Respiratory Disease Prevention
    • Prevention of Neurodegenerative Disease

    Overview of potential berberine risks and side effects:

    • Berberine is known to have an outstanding safety profile
    • Side effects may include cramping, diarrhea, flatulence, constipation and stomach pain
    • Berberine may also have an adverse interaction with certain prescription medications. Always consult your physician prior to use.

    How Does Berberine Work?

    Berberine is known to impact a wide range of cellular targets. These targets are like “on/off” switches for cellular activity. They can be proteins, nucleic acids, or any other structure or network within the body.

    Aptly named, these structures are often “targeted” by medical interventions. For example, things like medical devices and chemical compounds (both synthetic and plant-derived) are often designed to interact with these cellular targets to effect certain desirable outcomes. And in the field of longevity science specifically, such devices and chemicals are used to target any biological system that has the potential to safely extend lifespan while reducing the risk of age related disease.

    As cited above, berberine’s “harmonious distribution” across various essential biological targets appears to be its key mechanism of action. These targets include:

    • Insulin Receptors: By interacting with insulin receptors, berberine is thought to create new insulin receptors, improve insulin uptake, reduce insulin resistance, and curb the adverse health effects associated with diabetes.*
    • Low-density Lipoprotein (LDL) Receptors: By interacting with LDL receptors, berberine appears to reduce LDL “bad” cholesterol and corresponding risk of heart disease and stroke in the latter half of life.*
    • AMPK Pathway: AMPK is an enzyme often referred to as a “pathway” for its role in controlling certain aspects of cellular activity. By increasing AMPK pathway activation, berberine appears to help control cell growth, promote cellular autophagy, and reduce the incidence of inflammation and cancer related to cell death.*
    • Mitochondrial ATP Production: Adenosine triphosphate (ATP) is a critical chemical synthesized during everyday food metabolism and cardiovascular activity. Berberine appears to assist in this process while also helping to mitigate its toxic byproducts.*
    • Brown Fat Tissue: Brown adipose tissue is a unique type of body fat that becomes activated in times of extreme cold. Brown fat cells have more mitochondria compared to ordinary white fat cells, the latter being what most people think about when it comes to weight loss. Those extra mitochondria generate added body heat, which ultimately requires the body to burn more calories. In mice and animal studies, researchers have identified berberine as a potential obesity prevention tool for its ability to activate the calorie-burning power of brown fat.*

    This sweeping distribution and activity seems to enable berberine to deliver several beneficial actions. Anti-inflammatory, anti-diabetic, pro-cardiovascular, and potentially even anti-cancer benefits are among the most well researched.

    In addition to affecting these targets, berberine also appears to have potent antioxidant potential. Studies suggest this plant-derived alkaloid scavenges and neutralizes reactive oxygen species (ROS) by up-regulating two pathways that control cell survival signals: P13K/AKT/Bcl-2, and Nrf2/HO-1. That’s a key finding, as ROS are capable of causing cellular damage and disrupting healthy biological function. Over time, aggregate damage from ROS is believed to be a leading contributing factor to cancer, respiratory disease, neurodegenerative disease, and other age-related illnesses.

    *More information and study citations are provided in the Potential Health Benefits of Berberine and Potential Health Risks and Side Effects sections below.

    Berberine Dosages and Supplements

    Disclaimer: Always consult your health care professional prior to making changes in your diet or exercise regimen, including whether to use supplements containing berberine.

    When supplementing with berberine, there are a couple key factors to consider:

    • Common dosages range from 500mg to 1500mg daily, taken on an empty stomach
    • The body clears berberine quickly, so it’s recommended that dosage be spread out over the course of the day (e.g. 500mg three times daily, for a total of 1500mg)

    Berberine supplements are most commonly available as capsules, fluid tinctures, and as topical creams. In addition to 100% berberine formulations, the following foods and supplements are also known to be a good source of this potent alkaloid:

    • European barberry
    • Goldenseal
    • Goldthread
    • Oregon grape
    • Phellodendron (Amur cork tree)
    • Tree turmeric

    Potential Health Benefits of Berberine

    Improved Gut Health & Digestion

    Berberine elicits several responses in the gastrointestinal (GI) tract, which may set the stage for the many beneficial health effects noted downstream. To better understand this phenomenon, it helps to understand how the GI tract functions.

    The GI tract is often referred to as an organism of its own. The GI tract is composed of various types of microbiota, or microorganisms. These include helpful microbes, like bacteria, that aid in food digestion and nervous system function. The GI tract may also become home to harmful microbes, like parasites, that scavenge nutrients and can wreak havoc on holistic health.

    Maintaining balance and functionality within the GI tract is key, and that’s where berberine shines. In a 2017 animal study published in the peer-reviewed journal Metabolism, researchers found berberine to promote the growth of a special kind of bacteria that produces a chemical called butyrate.

    Butyrate is a fatty acid that plays a key role in metabolism and, as the researchers note, “enters the blood and reduces blood lipid and glucose levels”. This makes berberine a significant potential catalyst for not only energy production, but also the prevention of diseases typically associated with over-abundance of blood lipids and glucose– namely, cardiovascular disease and diabetes.

    Berberine’s potential anti-inflammatory and anti-cancer properties also seem to stem from interactions in the GI tract. In another animal study published by Frontiers in Pharmacology in 2017, researchers found berberine to regulate several key inflammatory factors. These include the anti-inflammatory cytokine IL-10 and tumor necrosis factor TNF-alpha. In addition to reducing low-grade inflammation, researchers also noted berberine may be essential in the “improvement of gut-derived hormones” that fortify intestinal walls and promote overall GI health.

    Reduced Inflammation

    As noted above, the anti-inflammatory effects of berberine begin in the GI tract. Additionally, several studies indicate berberine has an anti-inflammatory effect beyond the walls of the gut. In such cases, researchers, believe this mechanism of action is directly related to the alkaloid’s ability to reduce symptoms of inflammatory conditions and disease, like cardiovascular disease and metabolic disorders.

    One of the most comprehensive reviews on berberine was published by the European Society of Clinical Nutrition and Metabolism (ESPEN) in the online journal Clinical Nutrition. Twelve independent, randomly-controlled trials were reviewed in this 2020 meta-analysis. By measuring markers of systemic inflammation, like C-reactive protein (CRP), researchers found significant reductions in body weight, body mass index, waist circumference, and free flowing CRP levels among individuals treated with berberine. At the conclusion of the analysis, researchers note that berberine treatment may have also attenuated the symptoms experienced by those individuals with metabolic disorders.

    Diabetes Treatment and Prevention

    Berberine also appears to be a potential anti-diabetic compound. As early as 1988, berberine studies have shown the alkaloid’s ability to reduce blood glucose levels in patients with type-2 diabetes.

    As noted above, animal and human studies demonstrate berberine’s ability to promote healthy gut bacteria while also reducing inflammation. Both of these effects, it turns out, are also important when it comes to preventing insulin resistance and the development of diabetes.

    In an animal study published by the peer-reviewed journal OxiMed & Cellular Longevity in 2018, researchers note that an imbalance of gut bacteria combined with systemic inflammation are two key drivers of type-2 diabetes. Unlike juvenile diabetes, type-2 diabetes develops over time as the body becomes less efficient– and eventually incapable– of utilizing blood sugar. There is no cure, but weight loss and managing blood sugar are key components of living healthily with type-2 diabetes.

    Berberine appears to help with both. In the OxiMed & Cellular Longevity study referenced above, researchers note that berberine promotes the metabolism of glucose by balancing gut bacteria, increasing the expression of enzyme PI3K, and increasing expression of the protein GLUT2. This is important for two distinct groups of people.

    For individuals who currently have type-2 diabetes, berberine may help manage blood sugar and slow the progression of the disease. For those interested in promoting longevity and healthspan, berberine may help to prevent metabolic disorders like type-2 diabetes from developing in the first place.

    Reduced Insulin Resistance and Metabolic Disease Prevention

    In addition to promoting glucose metabolism, berberine also appears to reduce insulin resistance through antioxidant activity. This is a key insight into berberine’s potential anti-diabetic properties.

    Normally, diabetes is characterized by a progressive reduction in the body’s response to insulin (insulin resistance). When cells become resistant toward this essential hormone, glucose (sugar) can no longer be efficiently transferred from bloodstream to cells. Rather than being used for energy, sugar is left in the bloodstream and may cause several adverse health conditions over time. Excess body fat, high blood pressure, hypertension, and increased risk of cardiovascular disease and stroke are just a few examples of the metabolic diseases that can develop as a result of insulin resistance.

    Interestingly, insulin resistance is a primary condition that causes the development of type-2 diabetes. In other words, individuals do not have to be diabetic to develop insulin resistance and experience the adverse health effects of metabolic disease. As such, berberine appears to be a therapeutic alkaloid for not only treating diabetes symptoms specifically, but also for preventing metabolic diseases through mid and latter years of life.

    Obesity Prevention

    Berberine also appears to prevent obesity. This is likely a downstream effect of the GI, anti-inflammatory, and anti-diabetic health benefits explored in the sections above. Specifically:

    • In the GI tract, berberine promotes the production of butyrate, a fatty acid known to enter the blood stream and reduce blood lipids and glucose levels.*
    • In a 2020 meta-analysis of 12 independent studies, individuals treated with berberine experienced reductions in body weight, body mass index, and waist circumference.*
    • As an anti-diabetic, berberine appears to prevent insulin resistance and the metabolic diseases it causes.*

    *For study citations, please see Gut, Inflammation, and Diabetes sections above.

    Obesity has many contributing factors, which is why the vast distribution of berberine may help. By addressing a variety of factors ranging from blood lipids to insulin and inflammation, berberine appears to provide a multi-pronged approach to obesity prevention.

    Berberine also appears to improve the metabolic health of animals on a high fat diet. In a 2016 animal study published by Obesity Facts, researchers found that mice treated with berberine exhibited less weight gain, endogenous insulin production, and insulin resistance compared to the control group.

    Moreover, berberine appears to recruit and activate a unique type of fatty tissue called brown adipose tissue. In a 2019 study published by the journal Cell Death & Disease, berberine was found to promote the formation and activation of brown fat in both mice and human models.

    Recent studies on obesity and weight management have identified brown fat as a potential key to healthy weight management. That’s because brown fat has more mitochondria than ordinary fat, is used during thermogenesis (metabolism and heat production), and increases total energy (calorie) expenditure. Thus, increasing brown fat causes a corresponding increase in total daily calorie burn.

    All else being equal, this increased energy expenditure may cause a calorie deficit in which calories burned exceeds calories consumed throughout the day. And that’s critical to weight management, as health experts agree: Weight loss is all about maintaining a calorie deficit over time, and weight management requires eating just enough calories to sustain individual daily activity. By activating brown fat, berberine appears to assist with both.

    Prevention of Liver Disease

    As noted, a key aspect of berberine’s wide ranging health benefits seems to come from its vast distribution across various important biological targets. These include cellular mitochondria, AMPK pathway, and insulin and LDL receptors. Interestingly, berberine distribution occurs most predominantly in the liver, where it appears to exert specific and localized effects.

    Most notably, a 2016 study published by Scientific Reports in conjunction with the journal Nature found berberine to “significantly reduce inflammation, fibrosis, and levels of peroxides” in liver tissues of mice. As a result, mice treated with berberine exhibited a reduction in the mechanisms of lipid metabolism that ultimately drive liver disease. Commenting on the study, researchers note that berberine represents a serious potential therapeutic agent for preventing hepatic steatosis, or fatty liver disease, in both alcoholic and non-alcoholic individuals.

    Prevention of Cardiovascular Disease

    As cited above, berberine shows great therapeutic potential for improving gut health, digestion, inflammation, obesity, liver health, and various aspects of diabetes and metabolic disease. Not surprisingly, these outcomes appear to cause downstream effects that may also improve cardiovascular health.

    In 2015 article published by the peer-reviewed journal Chronic Diseases and Translational Medicine, researchers cite new and novel research documenting berberine’s many positive effects on the cardiovascular system. These include anti-heart failure, anti-hypertension, anti-hyperlipidemia, and anti-platelet aggregation. Notably, berberine appears to:

    • Reduce the risk of heart failure by preventing ventricular fibrillation (abnormal heart rhythm)
    • Increase cardiac output in heart failure models (a study design that specifically observes the impact of certain chemicals and drugs on hearts, as they fail in real time)
    • Relax the muscles of the heart, including the endothelium (inner membrane) and smooth muscle tissues
    • Reduce the incidence of irregular heart beat, or heart arrhythmia

    Researchers conclude the paper by acknowledging that, although berberine has been utilized in Traditional Chinese Medicine for more than 2,500 years, “recent discoveries have provided novel evidence that [berberine] may be considered a promising tool to counteract cardiovascular disorders”.

    Perhaps most powerful is a 2021 meta analysis published by the peer-reviewed journal Frontiers in Pharmacology that summarizes the “pharmacological research progress” of berberine and the prevention of cardiovascular disease. In it, researchers summarize an overwhelming amount of evidence that demonstrates berberine’s ability to improve heart and cardiovascular health. This includes prevention and treatment of the following:

    • Arrhythmia, or irregular heartbeat
    • Atherosclerosis, or cholesterol buildup in arterial walls
    • Hyperlipidemia, or high levels of fat in the blood (like cholesterol)
    • Hypertension, or high blood pressure
    • Ischemic heart disease, or coronary heart disease, in which blood flow to heart muscle is restricted
    • Myocarditis and cardiomyopathy, or inflammation and disease, respectively
    • Heart Failure

    Treats Diarrhea

    As a common alkaloid utilized by Traditional Chinese Medicine, Berberine has been used to treat gastrointestinal issues for over 2,000 years. Modern research has since validated this ancient wisdom, as demonstrated by a 2020 meta-analysis published by the journal Therapeutic Advances in Gastroenterology. In it, researchers examine 38 randomized controlled trials involving more than 3,900 participants.

    Results indicate berberine effectively treats diarrhea when used alone or in conjunction with antibiotics, especially when administered for 7 to 3 days.

    Alleviates Skin Diseases

    Berberine also appears to effectively treat two common skin conditions: Atopic dermatitis (eczema) and psoriasis.

    Atopic dermatitis (eczema)
    Atopic dermatitis, commonly known as eczema, is characterized by skin inflammation, rashes along the arms and knees, and itchiness. In an animal study published in 2021, researchers found berberine to treat atopic dermatitis by functioning as an anti-inflammatory while also alleviating itching, skin irritation, and other symptoms of eczema.

    Psoriasis
    Psoriasis is a condition characterized by the accumulation of skin cells that build up into itchy, dry patches. In a 2019 study published in the journal Cell Death and Disease, researchers found berberine to inhibit the expression of psoriasis by down-regulating the intracellular pathways responsible for its spread. Although more research is needed to identify the exact mechanisms of action, the study authors close the paper by acknowledging berberine “may serve as a potential therapeutic option for patients with psoriasis”.

    Respiratory Disease Prevention

    Recently, scientists have begun to closely examine the role of berberine in preventing respiratory diseases like chronic obstructive pulmonary disease (COPD), asthma, pulmonary fibrosis, and lung cancer. Research is limited, as this is a new and emerging area of study. However, researchers believe berberine has potential to help treat or prevent respiratory diseases by acting as an anti-inflammatory.

    In a 2007 study published by International Journal of Clinical and Experimental Medicine, researchers identify a key mechanism of action that explains how berberine might treat respiratory disease. By suppressing the inflammatory cytokines responsible for causing pulmonary (lung) inflammation, researchers believe berberine may someday play a vital role in treating and preventing various forms of lung disease.

    Prevention of Neurodegenerative Disease

    Neurodegenerative diseases like Alzheimer’s, Parkinson’s, and Huntington’s affect an estimated 50 million Americans each year. Worldwide, the United Nations estimates that number to be closer to 1 billion people. Such diseases are characterized by a progressive loss of nervous system function, which may manifest as severe impairments to speech, mobility, or cognitive function. Despite major advancements in technology and treatment, neurodegenerative diseases are often fatal, especially in under-developed regions.

    In the last decade, an increasing number of animal and human studies have linked all neurodegenerative diseases with a common risk factor: Reactive oxygen species (ROS). ROS are produced anywhere the body utilizes oxygen. That makes the brain especially vulnerable, as it continually demands large amounts of oxygen to function. Although more research is needed, consensus among leading researchers is that oxidative stress is a “key modulator in neurodegenerative disease“. But how?

    One way is by functioning as an AMPK agonist, or trigger. By targeting and activating the AMPK pathway, researchers believe berberine can prevent several conditions that contribute to neurodegenerative diseases, including:

    • Oxidative stress
    • Neuroinflammation
    • Mitochondrial disorders
    • Autophagy disorders
    • Disruption of neurovascular units

    Moreover, the study cited above also indicates that berberine’s AMPK activation causes several downstream effects that may also prevent neurological decline. Specifically, AMPK activation ignites several of the body’s oldest and most powerful survival circuits, including mTOR, SIRT1, and NF-KB pathways. Together, these circuits may help prevent neurological decline by alleviating chronic inflammation and preventing ROS damage throughout the life cycle.

    Potential Health Risks and Side Effects

    Berberine has been used for thousands of years in Traditional Chinese Medicine, and it is known to be exceptionally safe.

    Most common side effects include cramping, diarrhea, flatulence, constipation, and stomach pain.

    Nevertheless, Berberine may have an adverse interaction with certain prescription medications. For example, its effect on insulin may lead to unwanted interactions with medications designed to lower blood sugar levels. As with any change in your diet or nutrition regimen, always consult your physician prior to taking a berberine supplement.

    Conclusion: Berberine Brings Harmony, Encourages Healthy Aging

    Traditional Chinese Medicine has utilized berberine for centuries to promote health and treat various ailments. Today, a growing body of animal and human research supports this powerful plant compound’s effectiveness in treating and preventing a variety of conditions, ranging from diabetes to heart, lung, liver, and neurodegenerative diseases.

    Harmonious distribution, wide reaching health benefits, and an outstanding safety profile make berberine an essential addition to any health regimen.