Metformin, Berberine, or Inositol for PCOS?
By Amy Medling, founder of PCOS Diva
The question of whether to choose metformin, berberine, or inositol for treatment of Polycystic Ovary Syndrome (PCOS) comes up a lot. Doctors often reflexively choose the pharmaceutical (metformin), and many have had great success with suppressing their PCOS symptoms with the drug. Others choose the natural supplement route of taking berberine and/or inositol since they are proven to work as well with none of the side effects common to metformin and tackle the root of the syndrome. So, what are these substances and how do they compare? Here is your breakdown of metformin, berberine, and inositol, how they each work, and what you could expect.
Inositol
What is inositol?
Inositol is a class of B-vitamins that naturally occur in many of the foods we consume such as fruits, legumes, vegetables, nuts, buckwheat, and beans. Two of the 9 forms of inositol (MYO and D-Chiro) have special insulin sensitizing capabilities and are important “second messengers” for insulin receptors.
How does inositol work?
Inositol helps to improve your insulin balance and reduce insulin resistance. MYO (MI) and D-Chiro (DCI) inositols are critical players in insulin signaling, and the disruption in this signaling, due to a lack of one or the other, leads researchers to believe that inositol is a key component in insulin resistance. Unfortunately, women with PCOS often have a breakdown in this process. Our bodies have difficulty converting inositol from our food into MYO and DCI, or we excrete too much DCI and cannot produce enough to replace it. This causes the breakdown in insulin processing. This situation is even more likely if you have first-degree diabetic relatives.
As you may know, insulin resistance (IR) triggers increased testosterone. IR and high testosterone are common symptoms in women with PCOS, which cascade into a host of hormone related health issues ranging from difficulty with fertility to acne and hair loss. Studies have shown that women with PCOS who take an inositol supplement each day will reduce their insulin resistance, improve their hormone levels, and have more regular menstrual cycles. Inositol supplementation also supports normal lipid (blood fat) levels and promotes egg quality in women trying to become pregnant. In addition, inositol is a lipotropic agent which helps your body remove fats from your organs and blood. While inositol is most thought of for restoring menstrual cycles and fertility, replacing clomiphene or metformin, current research promises a role well beyond these symptoms.
For more about MYO inositol, read, “7 Benefits of Myo- Inositol for PCOS”
For more about D-Chiro inositol, read, “Uncovering the Secrets of D-chiro- inositol for PCOS”
Combination of MYO & D-chiro inositol
As with so many things in your body, it is all about balance. The natural ratio of MYO to DCI in your plasma is 40:1. The goal is to maintain that ratio for optimal performance. Adding too much of one or the other will throw off your balance and then you are back to square one. Studies show that, “MI/DCI in a combination reproducing the plasma physiological ratio (40:1), represents a promising alternative in achieving better clinical results, by counteracting PCOS at both systematic and ovary level.” In fact, a recent study revealed that,
“Myo-inositol+D-chiro-inositol showed significantly better results in terms of weight reduction, resumption of spontaneous ovulation, and spontaneous pregnancy than metformin in polycystic ovary syndrome patients.”
In addition, women with PCOS undergoing IVF may especially benefit. One study found that, “only the combined therapy was able to improve oocyte and embryo quality as well as pregnancy rates.” So in summary, “The combined administration of MI and DCI in physiological plasma ratio (40:1) should be considered as the first line approach on PCOS overweight patients, being able to reduce the metabolic and clinical alteration of PCOS and, therefore, reduce the risk of metabolic syndrome.” In fact, the greatest benefit to controlling insulin resistance no matter your weight comes with the balanced (40:1 ratio) and combined use of MYO & D-chiro inositols. I choose to take Ovasitol for many reasons including that it comes in the 40:1 ratio. For more about Ovasitol, read, “Why I (Still) Take Ovasitol.”
Are there any side effects to taking inositol?
The short answer is no. Occasionally, at a very high dose of MYO, one may experience mild GI side effects such as nausea, gas or diarrhea. It should not interact with your other medications or supplements. During pregnancy and while breastfeeding, you may continue taking inositol, and studies show that it may reduce gestational diabetes. As always, please consult your healthcare team before beginning any medication or supplement.
Berberine:
What is berberine?
Berberine is a compound which can be extracted from many different plants including goldenseal, Oregon grape, barberry, yellow root, and philodendron. Due to its bitter taste, it is typically taken in capsule form.
How does berberine work?
Insulin– Berberine may be best known for its ability to manage insulin levels. Berberine works in your body on a molecular level. One of its main functions is to activate AMPK, an enzyme which regulates metabolism. Tests show that berberine consistently lowers fasting glucose, fasting insulin, post-prandial glucose, and HbA1c.
In addition, berberine outperforms Metformin at regulating insulin without many of the gastrointestinal side effects that come with the drug. In fact, berberine also out performs Metformin in the reduction of cardiovascular risk factors including waist circumference, waist-to-hip ratio, and dyslipidemia, triglycerides, total and LDL cholesterol, and increasing HDL cholesterol. What’s even better is that berberine is normoglycemic, which means that it only reduces blood sugar levels if they are elevated.
Androgen Regulation– Berberine has been shown to improve insulin resistance in theca and granulosa cells in a similar way to metformin, and therefore, researchers believe, it has the same androgen production regulation effects without the side-effects of metformin. This is of particular concern to women with PCOS because hyperandrogenism is responsible for many of PCOS’s most challenging symptoms including hirsutism (excessive hair growth), acne (particularly on the face, back and chest), and acanthosis nigricans (areas of hyperpigmented, velvety plaques typically found in the underarm, neck, and groin areas).
Acne– Research demonstrates that due to its antilipogenic effect on the sebaceous glands, berberine is considered a safe, well-tolerated, and effective choice in people with moderate to severe acne. Studies have shown an improvement in acne by as much as 45% after only 4 weeks. In fact, use of berberine is proven to speed the healing of scars and prevent future outbreaks of acne.
Gut Health– Berberine has demonstrated significant capabilities in improvement of gut health due to its antimicrobial activity. Studies demonstrate that the supplement will enrich short-chain fatty acid (SCFA)-producing bacteria which leads to improvement in gut barrier functions, alleviating inflammation, or creating an unwelcoming environment for pathogens, which may also help to improve obesity and insulin resistance-related metabolic abnormalities.
A Word of Caution
Berberine is generally considered to be safe and well tolerated, but there are a few cautions to consider. High doses of berberine may cause poor intestinal uptake resulting in cramping and diarrhea. To prevent discomfort, take the recommended daily dosage throughout the day, not all at once. Berberine may interact with antibiotics such as azithromycin and clarithtomycin. Berberine may limit uptake of metformin. Berberine is not safe to take during pregnancy. It likely crosses the placental barrier and may harm the baby. Berberine is not safe to take when nursing because it can be transferred to the baby in breast. Be cautious if you take other prescription medications such as antidepressants, beta-blockers, or immunosuppressants because berberine can alter the levels of those medications in your bloodstream.
For more about berberine for PCOS, read, “Exciting New Treatment for PCOS – Berberine.” 
Metformin
Metformin is a pharmaceutical drug commonly prescribed to treat diabetes and pre-diabetes. Doctors also often prescribe it as treatment for PCOS.
How Metformin Works:
Metformin works through a variety of mechanisms. First, it alters the gut microbiome. The gut microbiome has been found to be critical to insulin/glucose regulation. Low grade generalized inflammation in fat tissues or in the liver is an important factor in insulin resistance, a condition common to PCOS. The wrong intestinal bacteria are a major source of inflammatory particles derived from the “wrong” bacteria, which can cause inflammation both within the bowel itself, in the liver, in fat tissue, and across the entire body. With the wrong bacteria present in the gut, the protective mucous coating of the inside lining of the gut, produced by a species of bacteria call Akkermansia, is absent, and the result is damage to the lining cells of the gut, and to the body as a whole. Certain cells in the gut walls, called Paneth cells, produce antimicrobial peptides. Metformin appears to increase the abundance of Akkermansia bacteria, thereby promoting the protective mucous coating and supporting the function of the important Paneth cells.
Metformin also appears to work by creating low grade damage to mitochondria, the energy producing factories of cells. By creating this mild damage, the pathways for fat burning and cellular rejuvenation are stimulated, which can lead to more effective glucose regulation.
The Concerns with Metformin:
Though it can have its place, it never cures insulin resistance or diabetes, doesn’t seem to improve fertility success or ovulation, and doesn’t give meaningful weight loss.
In terms of facilitating success with IVF, when directly compared with berberine, berberine yielded more successful IVF babies than did metformin when used with patients with PCOS.
The most common side effect of metformin is nausea and gastrointestinal symptoms stemming from its use. Metformin also depletes the body of Vitamin B12 and other nutrients. A shortage of B12 is associated with nerve pain, cognitive dysfunction, and anemias. B12 is also critical for many of the detoxification pathways and for DNA stability.
It is now well recognized that metformin is an endocrine disruptor. That means that it is a chemical which acts as an abnormal hormone-like substance, creating different and unexpected symptoms and effects throughout the body.
Finally, in early 2020, the US Food & Drug Administration issued a recall of metformin ER because the agency’s testing showed N-Nitrosodimethylamine (NDMA) above the acceptable intake limit in certain lots.[i] NDMA is believed to cause cancer.
For more about metformin and PCOS, read, “What You Don’t Know About Metformin.”
What works better for PCOS – metformin, inositol, or berberine?
Metformin v. Inositol
Studies conducted within the last decade all point to inositol as a natural treatment to symptoms of insulin resistance, with the latest research proving an efficacy similar to metformin for PCOS patients. Even with similar dosages, you are not as likely to have adverse reactions to inositol than you would with metformin.
For more about using metformin v. inositol, read, “Myo-Inositol vs Metformin for PCOS.”
Metformin v. Berberine
Studies indicate that berberine outperforms metformin and without the side effects and with the added anti-inflammatory, immunity boosting, and cholesterol lowering benefits. In one study [1], researchers compared berberine to the conventional medication metformin. After three months, both the berberine and metformin groups saw improvements in insulin, body weight and testosterone. The berberine group outperformed metformin in reduction of waist circumference and free androgen index. In a 2014 study [2], 150 infertile women with PCOS were assigned to three treatment groups: metformin, berberine and placebo during three months prior to IVF. Both the berberine and metformin groups saw improvements in insulin, glucose, testosterone, and free androgen index. The berberine group achieved more live births had fewer side effects compared to metformin.
Final Word on Metformin, Berberine, or Inositol for PCOS
There is no single correct answer. The right supplement or drug for you is entirely dependent upon your body’s unique chemistry. Talk to your doctor about your alternatives. Be ready to educate them about inositol and berberine though. Many doctors default to pharmaceuticals because that is how they are trained.
Regardless of whether you choose inositol, berberine, or metformin, it cannot be your only line of treatment. All research indicates that the first line of treatment of PCOS is a PCOS-friendly diet and lifestyle.
Amy Medling, best-selling author of Healing PCOS and certified health coach, specializes in working with women with Polycystic Ovary Syndrome (PCOS), who are frustrated and have lost all hope when the only solution their doctors offer is to lose weight, take a pill, and live with their symptoms. In response, Amy founded PCOS Diva and developed a proven protocol of supplements, diet, and lifestyle programs that offer women tools to help gain control of their PCOS and regain their fertility, femininity, health, and happiness.
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