The Dark Side Of Metformin: A “Longevity Wonder Drug” That Promises to Extend Life For A Nickel A Pop.

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February 2019 update from Ben: please go listen to my podcast with Jay Campbell, in which we discuss updates on the information provided below, particularly:

The fear of lactic acidosis happening was based on a study from the 1940s in a massively compromised patient cohort. These patients were in end-stage renal failure and also obese and diabetic. We must be mindful that correlation does not equate to causation. While metformin has been contraindicated in moderate and severe renal impairment, the reported incidence of lactic acidosis in clinical practice has proved to be very low (fewer than 10 cases per 100,000 patients).

The studies on metformin and cardiovascular risk were also performed on a thoroughly compromised patient population group of morbidly obese diabetics who were using anywhere from 6-9 grams of metformin per day – three to five times the recommended and commonly used dose. Other studies show it’s actually the opposite: that metformin may actually reverse mitochondrial dysfunction!

Regarding B12: both B12 and folate are incredibly simple compounds to supplement with, and can easily be stacked with a metformin protocol to avoid these deficiency issues.

There have also been studies out of Taiwan showing that metformin taken by diabetics for long periods of time (12 years or longer) can nearly double the risk of Alzheimer’s and Parkinson’s, but – similar to the studies on lactic acidosis – this study involved heavy use for extended periods of time.

Regarding liver toxicity, it turns out that these issues with metformin occur in people who already have a compromised liver.

Next comes the potential impact that metformin may have on exercise performance. In the study “Impact of metformin on peak aerobic capacity”, it was shown that metformin can significantly decrease VO2 max (–2.7%), peak heart rate (–2.0%), peak ventilation (–6.2%), peak resting energy expenditure (–3.0%), and actual exercise duration (–4.1%). While these reductions were certainly slight, and potentially non-significant for the average exercise enthusiasts, they do suggest that for a professional athlete (especially a professional endurance athlete), the use of metformin may spell the difference between a 1st place finish and not even making the podium!

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Finally, there’s the concern that metformin causes GI upset. But this seems to happen only in people with bacterial imbalances disc and, based on recent studies, may occur because metformin is working directly to favorably alter the microbiota. Research has shown that metformin can indeed alter the gut composition in a favorable manner by increasing levels of several different short-chain fatty acid (SFCA) bacteria and by decreasing inflammation in the gut in a manner that actually increases insulin sensitivity and lowers blood glucose! However, one newer study from September 2018 does suggest that metformin causes an “increase in abundance of opportunistic pathogens and further triggers the occurrence of side effects associated with the observed dysbiosis”. 

I’ll sum it up here: don’t use metformin if you have liver and kidney issues, and definitely don’t overdose with metformin. If you get gut discomfort while using metformin, consider waiting it out to see if your gut flora becomes balanced and your symptoms subside, which typically takes 8 to 12 weeks, and proceed with caution if you have any prexisting gut issues due to potential for bacterial imbalances in the gut flora. If you use metformin, supplement with vitamin B12 and, if you’re a woman, monitor your folate levels and consider supplementation with a good multivitamin that contains a natural form of folate like methyltetrahydrofolate (MTHF). Finally, if you’re a professional athlete or aerobic performance is very high on the totem pole for you, I’d avoid metformin.


The modern supplement market is chock full of miracle pills, wonder potions, and injections that will “make you look and feel 10 years younger”. And the advertisements can be alluring – as far back as human memory can reach, long-lasting youthfulness has infatuated scientists, witch doctors, explorers and average Joes alike.

Just look at the number of legends surrounding the fabled Fountain of Youth. And even though the age of intrepid explorers and rogue buccaneers searching for those aforementioned waters of life has passed, the obsession with the underlying idea of immortality remains (this intriguing immortality section of Vice is a perfect example). After all, who doesn’t want to live longer and enjoy lasting health?

Unfortunately, for the entire race of man, a seemingly unending list of bacteria, viruses, neurological disorders, and fatal conditions assail the human body day in and day out. Of late, as I become increasingly disenchanted with the often unhealthy pursuit of a six pack-abs, mutant lungs and ripped biceps, I’ve instead turned myself into a student of anti-aging and longevity tactics that can actually help to stave off these assailants and allow you to live longer and feel really good doing it…tactics that include:

-Basic strategies outlined in books such as Blue Zones by Dan Buettner, including high wild plant intake, avoidance of packaged foods, calorie restriction, social support, family, gratitude (my own recent obsession) and relationships.

-Intermittent fasting, cyclic ketogenesis, protein-sparing modified fasts, and other forms of caloric and selective macronutrient restriction like I discuss here.

-Strategic use of “hormetic” stressors, including hyperoxygenation, wild plant and herb consumption, pulsing molecular hydrogen, beta-hydroxy butyrate and ketone supplementation for longevity, cold thermogenesis and cryotherapy, heat and sauna, UVA and UVB radiation.

-Little known stem cell enhancing and stem cell supporting nutrients and foods, including colostrum, chlorella, curcumin, marine phytoplankton, aloe vera, coffeeberry fruit extract and moringa (stay tuned for a podcast coming soon on many of these superfoods and the best way to find them).

-Stem cell transplants, along with peptides, prolotherapy, platelet rich plasma injections and placenta delivery options to mimic the anti-aging effects of stem cells (just watch this recent Weekly Roundup to see me injecting pig placenta and cow thymus into my own butt cheeks).

-Blood transfusions from umbilical or placental sources to simulate fascinating research in which the blood from young mice injected into old mice caused a significant anti-aging effect.

-The sweet spot between excess growth hormone and enough growth hormone to maintain anabolism as one ages, including strategies such as bioidentical hormone replacement therapy, colostrum, dairy extracts, injectable growth hormone precursors and growth hormone pulsing compounds and more.

-Upregulating intake of activators of “sirtuins”, a family of genes that increase the efficiency of an organism to fight stress like excess heat or lack of food maintaining its power of natural defense, maximize the chances of survival of an organism, increase longevity and health if remaining activated, and deemed as “longevity genes” because they lower risk of diseases causing old age. These include blueberry, dark chocolate, green tea and resveratrol.

-Biohacks and strategies that address mitochondrial degradation, mitochondrial aging, and excessive formation of reactive oxygen species (ROS’s), including Pau D’ Arco bark tea, NAD injections and supplements, fenugreek, fish oil, CoEnzyme Q10, glutathione injections and supplements and other potent antioxidants, all of which can serve as compounds that specifically limit or mitigate mitochondrial damage.

But in today’s article, in particular, I want to hone in on one of the most prevalent of the conditions that threatens longevity today…

…specifically diabetes (and overall dysregulation in blood sugar in general).

This is, in my opinion, one of the biggest leading causes of chronic disease and aging in humans. As a matter of fact, my brilliant friend, surgeon and longevity physician Dr. Peter Attia has said in the past in this fascinating interview on the eight keys to longevity that “…the name of the game is glucose disposal. Can you maintain a low average level of glucose and a low variance of glucose and a low area under the curve of insulin?”

In other words, despite any other anti-aging measures you pursue, if fluctuations in blood sugar or high blood sugar overall are left untreated, it can lead to a life cut short, depriving you of the long years that you could have with your family and friends. Sadly, just last week a new CDC report revealed that more than 100 million Americans have diabetes or “pre”-diabetes (basically pre-diabetes is chronically elevated blood sugar).

I would know.

For example, according to my 23andme genetic testing results, I have a 27% higher risk for Type II diabetes compared to the general population. That’s one of the major reasons why, in the past, I’ve published articles like “The Ultimate Guide To Biohacking Your Blood Sugar Levels“, one of the more comprehensive articles I’ve written on exercises, workouts and biohacks to lower your blood sugar levels. It’s also why I have a keen interest in so-called caloric restriction mimetic drugs, supplements and herbs, including rapamycin, MitoQ, resveratrol, pterostilbene, beta-hydroxybutyrate, along with other ketones and additional traditional blood sugar stabilizing nutrients such as fenugreek, bitter melon extract, ceylon cinnamon and apple cider vinegar.

Not surprisingly, pharmacologists and the pharmaceutical industry have developed robust chemical defenses that counteract the longevity-inhibiting effect of diabetes, and potentially go above and beyond blood sugar regulation when it comes to anti-aging. One such chemical defense has been the darling of health news, and you’ve no doubt heard of it.

It’s called metformin.

Metformin was the subject of a recent article I tweeted entitled “Forget The Blood Of Teens. This Pill Promises To Extend Life For A Nickel A Pop”.

In that article, it is reported how Tim Ferriss, in his recent book Tools of Titans, estimates that at least a dozen of the billionaires, icons, and world-class performers in the book take metformin. A member of the anti-aging panel at the Vatican, Robert Hariri, cofounder and president of genetic sequencing pioneer Craig Venter’s Human Longevity Cellular Therapeutics and Ray Kurzweil, of Singularity fame, along with Ned David, cofounder of Silicon Valley startup Unity Biotechnology (which is developing its own anti-aging drugs) all also take metformin.

But is metformin all it’s cracked up to be? Are the host of longevity physicians and anti-aging researchers who are now popping this pill making a big mistake? Are there safer alternatives? In this article, you’ll discover the answers, along with the little-known dark side to metformin.

Enter Metformin

Metformin has been one of the most popular prescriptions for diabetes over the past couple decades. It belongs to the biguanide compound family, which, as a group, has been used to treat diabetes since the 1950’s. While they don’t necessarily alter insulin secretion, they do improve insulin sensitivity to reduce blood glucose levels. Metformin is particularly effective at improving glycemic control, and also has a low risk of hypoglycemia. It exerts its glucose-lowering effect primarily by inhibiting hepatic gluconeogenesis (which you’ll hear more about further on) and by opposing the action of glucagon.

Metformin has a wide array of benefits that often go beyond the treatment of diabetes. One study observed its effect on nonalcoholic fatty liver disease (NAFLD) compared to vitamin E treatment or prescriptive diet. Over the course of the 12-month study, the control groups were given either vitamin E or treated with a prescriptive, weight-reducing diet. The physiological factors measured were liver enzymes, insulin resistance, parameters of the metabolic syndrome, and histology. All three groups experienced certain improvements, such as weight loss. But the effects in the metformin group were greater, and they experienced significant decreases in liver fat, necroinflammation (inflammation and cell death due to disease), and fibrosis (the thickening or scarring of tissue, particularly connective tissue, due to disease or physical stress).

Another study demonstrated the effectiveness of metformin and lifestyle (low-calorie, low-fat diet plus 150 minutes of moderate physical activity per week) on the prevention of type 2 diabetes. The lifestyle intervention treatment was the most effective, reducing the incidence of diabetes by 58%. The metformin was not quite as effective, but still powerful, with a significant reduction in diabetes incidence of 31%.

Metformin is so effective at preventing and treating diabetes because of its effect on gluconeogenesis, which occurs predominantly in the liver, and the consequent effect on hyperglycemia. Gluconeogenesis is the biosynthesis of glucose from sources other than glycogen, and is sometimes referred to as endogenous glucose production. This process requires carbon molecules and it gets the necessary carbon from pyruvate, lactate, glycerol, and the amino acids alanine and glutamine. Lactate is metabolized in what’s called the Cori Cycle as an anaerobic byproduct of glycolysis that the liver turns back into more glucose.

Metformin treatment can reduce hepatic (liver) glucose output by 0.7 mg per kilogram per minute and the amount of glucose produced from lactate by 0.2 mg per kilogram per minute (lactate contributes to about 60% of overall glucose production). Combining the effect on both processes, metformin reduces total hepatic glucose output by approximately 75%, making it a powerful tool against hyperglycemia. It also inhibits mitochondrial respiration (which is responsible for ATP/cellular energy production), and by so doing, forces an increase in glycolysis to generate energy. Glycolysis is the process that triggers carbohydrate/sugar metabolism to produce pyruvate which can be used either in aerobic or anaerobic respiration, as conditions require. So by forcing the body to revert from mitochondrial energy production to glycolysis, metformin further helps to reduce hyperglycemia.

The effects of metformin extend beyond the liver though. For example, it can have a significant inhibitory effect on the absorption of ingested glucose through the intestine, which would seem to make it a great treatment to take following a carbohydrate-heavy meal. At the same time, the metformin that settles in the intestine results in an increased utilization of glucose in the blood by the digestive tract. The highest concentration of metformin is found in various parts of the intestine, and because biguanides like metformin stimulate greater insulin sensitivity, there’s an insulin-mediated glucose utilization in the intestines that doesn’t occur anywhere else. One study even observed the drug’s effect on the suppression of intestinal polyp formation in mice, and found that it might act, in the future, as a chemopreventive agent for colorectal cancer.

Metformin is also associated with reduced risk of cancer in general by inhibiting mTOR (mammalian target of rapamycin). MTOR is a complex that regulates protein synthesis when the body has an abundance of nutrients and energy, notably, carbohydrates and insulin; it increases energy production, but also, naturally, creates more waste and junk products. It’s sometimes necessary to repair muscle tissue and improve certain aspects of cognition, but then its levels need to be checked and lowered to increase longevity and decrease cancer risk and inflammation.

When mTOR levels are elevated for extended periods, it increases what’s called “angiogenesis”, the process by which new blood vessels form from existing ones. This process allows cancer to grow and spread. Elevated mTOR levels also cause Type 1 T-helper cells to stimulate greater macrophage activity as an immunological response, which, in turn, increases intestinal inflammation. By allowing insulin levels to stay low by increasing the body’s sensitivity to deal with carbohydrates and sugars, metformin prevents mTOR levels from being raised too much or too often, which contributes to longevity and life-long health.

Hence metformin’s recent rise to fame as the next new potent anti-aging drug – a drug many physicians, anti-aging researchers and Silicon Valley executives are now popping like candy.

The Dark Side Of Metformin

Metformin seems like a pretty powerful tool. So what’s the problem?

Well, turns out that there’s all kinds of problems with metformin. In recent years, evidence has accumulated that metformin may not be all it’s cracked up to be. Or even if it does what it claims to do, it also has a number of adverse side effects, and up until now, pharmaceutical companies have just sugar-coated the drug’s effects.

For example, biguanides like metformin increase the generation of lactate, which can enter the circulation and produce lactic acidosis. The study “Fatty acids revert the inhibition of respiration caused by the antidiabetic drug metformin to facilitate their mitochondrial β-oxidation” describes this metformin effect on lactate production. But before getting into that, a quick note on phenformin. Phenformin is another member of the biguanide family and was a popular medication for diabetes starting in the 1950’s, but was withdrawn from clinical use in the 1970’s once it was discovered that it caused severe lactic acidosis. And even though phenformin is associated with a 10- to 20-fold greater incidence of lactic acidosis than its relative, metformin’s effects are still significant.

Despite being the most commonly prescribed drug for the treatment of type II diabetes for more than five decades, the bioenergetic mechanisms underlying metformin activity remain largely unknown. This ignorance of the inner workings of the drug have triggered many endeavors to uncover how exactly it works – but the results are often contradictory. The study “Cardiovascular and metabolic effects of metformin in patients with type 1 diabetes (REMOVAL): a double-blind, randomized, placebo-controlled trial” found that while metformin may play a very wide role in managing cardiovascular risks, it doesn’t necessarily improve glycemia, and it had no average effect on insulin requirement. In fact, while there were two deaths in the placebo group, there were five among the patients allocated to metformin.

But, the cardiovascular risk management also falls under scrutiny under certain conditions. True, metformin may be beneficial when used on its own. But, according to the study “Reappraisal of Metformin Efficacy in the Treatment of Type 2 Diabetes”, when combined with sulphonylurea (another common antidiabetic medication), metformin can actually result in an increased risk of cardiovascular complications and all-cause mortality. Studies are inconclusive at the time being, but the drug has been shown to have no proven efficacy against microvascular complications. And the possibility that metformin is not effective shouldn’t be dismissed out of hand. After all, the first molecule of this type, phenformin, did induce cardiovascular risk, and pharmacologically speaking, there’s little difference between phenformin and metformin.

All that to say, the specific efficacy of metformin to prevent death or cardiovascular disease has not been proven beyond reasonable doubt by current studies. So metformin may not be the best comparator for evaluating hypoglycemic drugs – and that’s not even the end of the story.

Metformin can also cause a deficiency of vitamin B-12 levels. The study “Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency” observed this effect. While the drug did cause reported improvements in cardiovascular morbidity and mortality (but, as you’ve seen, that’s already been called into question), it stimulated vitamin B-12 malabsorption. Decreased B-12 concentrations can cause increased homocysteine concentrations, which is, surprise, an independent risk factor for cardiovascular disease, particularly among individuals with type 2 diabetes. During the 52 months of the study, the placebo group experienced an increase in vitamin B-12 concentrations, while the metformin group experienced an average 19% decrease in B-12 concentrations, a decrease which continues to grow over time. While the lower B-12 concentrations were not a novel idea, the progressive nature was – they can result in macrocytic anemia, neuropathy, and mental changes, potentially making metformin a dangerous treatment to use.

Another study, “Metformin and Exercise in Type 2 Diabetes”, determined the effects of metformin on the metabolic response to sub-maximal exercise, the effect of exercise (relevant to activity patterns of type 2 diabetics) on plasma metformin concentrations, and the interaction between metformin and exercise on the response to a standardized meal. There is evidence that suggests that the benefits of exercise and metformin aren’t cumulative. In a study whose results were noted in this one, the reductions in diabetic risk were similar in a lifestyle that combined metformin and lifestyle modifications to the metformin or lifestyle alone groups. And in fact, the two adjustments may have contradictory effects on diabetes. First, metformin reduces blood glucose levels. But exercise tends to increase levels of glucagon, the hormone that deals with low blood sugar. When the two are combined, glucagon concentrations become significantly higher as the body tries to compensate for the effect of metformin. Second, by increasing the heart rate, metformin has the potential to lower some patients’ selected exercise intensity, which means it could lead to the prescription of lower exercise workloads than are commonly recommended. So, the combination of exercise and metformin, both common prescriptions for diabetics, is likely less effective at lowering the glycemic response to a meal than metformin alone.

There have even been a handful of reports of metformin-induced hepatotoxicity (toxicity in the liver). In a case of nonalcoholic liver disease, metformin was pegged as the cause of jaundice, nausea, fatigue, and unintentional weight loss, two weeks after initiating treatment, due to abnormalities in liver enzymes caused by the drug. Another case involved a 73-year old Japanese woman who experienced fatigue, jaundice, nausea, vomiting, anorexia, and abdominal pain due to severe hepatotoxicity that resulted from metformin.

I recently asked Dr. Dallas Clouatre, a well-established author and consultant in the alternative and complementary medicine and nutrition field and my guest on the podcast episode How Low-Fat Diets Make You Fat (the same author who, incidentally, introduced me to the potent alternative to metformin I’m going to fill you in on briefly), and here’s what he had to say:

“My thoughts on metformin are that it is interesting but over-hyped. Keep in mind that it works primarily on the liver (30% of glucose clearance from meals) and not on the peripheral tissues (70% of glucose clearance). It likely does promote a longer “health span” given that lowering insulin and IGF-1 along with mTOR, typical of caloric restriction and of those who naturally live to extreme old age, is usually a good thing. Of course, any item that keeps insulin levels low along with keeping blood glucose in the low-normal range will lower mTOR. Downsides of metformin include reduced efficacy with advancing age, reduced efficacy with prolonged use, and GI-tract issues in some individuals. Given that rehabilitation of the mitochondrial electron transport Complex I is a normal function of a good night’s sleep, for me, it is difficult to suggest the chronic intake of a drug that works by gumming up a natural process of the body.”

So where does this all leave metformin?

Despite the 20 years of positive clinical observations on metformin, these recent studies and the information above, in my opinion, have called its efficacy and overall health benefits into question. Perhaps it’s time to broaden the horizons and look to natural alternatives that can have very similar antidiabetic, blood sugar stabilizing and longevity-enhancing effects as metformin, but without the unpleasant side effects. 

Exit Metformin: Enter A Natural Dietary Approach To Blood Sugar Stabilization & Anti-Aging

The movement to a dietary approach to medicine has been gaining momentum for a long while now, and for good reason. When you hear of stories like that of Dr. Terry Wahls, who healed herself of a chronic progressive neurological disorder – secondary multiple sclerosis – by shifting to a nutrient-dense, high-fat diet, it’s difficult not to see the benefits of good eating.

Then there are the people who inhabit the western region of China on the slopes of the Himalayas – Bama County. This place is famous for the longevity of its inhabitants. In the year 2000, there were at least 79 men and women over one hundred years old, and still in good health, among a population of fewer than 230,000 people. That’s 3.52 centenarians per ten thousand people, the highest concentration anywhere in the world.

The residents, and some medical researchers attribute their long lives to a plant known locally as “shilianhua”, and known in English as the “rock lotus” or the “stone lotus”. For hundreds of years, it’s been used both as food and as a medicinal herb in the Bama region to treat a variety of conditions. And it has massive longevity benefits.

Only two mechanisms have been shown to be successful in promoting longevity, like that of the Bama region people, in higher organisms. The first lowers the levels of insulin and insulin-like growth factor 1. The second restricts calories, which usually has, as one result, a reduction of circulating insulin levels. The rock lotus influences both of these mechanisms; it also reportedly improves liver function. It’s been found that the rock lotus reduced blood sugar levels, which causes the reduction in insulin levels and relief of diabetic symptoms. In fact, it can reduce blood sugar levels by up to 30%, helping people in China and elsewhere to take their health into their own hands.

Another similar wild plant is bitter melon, also known as “goya” in Japan.

Bitter melon has only positives, as far as I am concerned. It’s fresh on my mind. At the time that I’m writing this article, I just returned from New York City, where I had the pleasure to spend quite a bit of time with Chef David Bouley, a world-famous Japanese cuisine expert who frequently travels to Asia to study what food consumption and dietary habits allow areas such as Okinawa to be such longevity hotspots. And one of the large bags of tea he brought back with him and gave to me was comprised of the same compound they ate in copious quantities before nearly every meal – you guessed it – bitter melon extract. 

But I already knew of bitter melon. I’ve personally been using it in the form of a potent tiny capsule called Kion Lean – a combination of the aforementioned rock lotus extract and bitter melon extract – to manage my postprandial blood glucose levels for nearly three years.

Taxonomically known as Momordica charantia, bitter melon may be an effective alternative to biguanides from metformin in controlling blood sugar levels and regulating blood pressure. Although the precise mechanism by which it works (whether it’s through regulation of insulin release or altered glucose metabolism and its insulin-like effect) is not known, bitter melon naturally contains antidiabetic compounds like charantin, vicine, and polypeptide-p, plus some other health-boosting components like antioxidants.

Bitter melon is a popular treatment for diabetes and similar conditions among the indigenous people of Asia, South America, India, and East Africa. As noted earlier, it’s known particularly well in Okinawa, Japan. Okinawa, like the Bama County, is one of the world’s “blue zones”, an area where the people group lives unusually long, and it’s also where some of the longest-lived people on the planet live.

In places like Okinawa, almost every part of the bitter melon has been used in traditional medicine, including the fruit, leaves, vines, seeds, and roots. It’s used to treat everything from microbial infections to digestive issues, stimulate menstruation, heal wounds, reduce inflammation and fevers, deal with hypertension, and it’s even been used as a laxative and emetic. It also activates cellular machinery to regulate energy production (particularly AMP-activated protein kinase) and the way fats are processed by the liver.

Centuries of oral consumption have demonstrated that bitter melon is both safe and effective. And on top of all those other conditions, according to a number of animal studies, it can even reduce insulin resistance and protect against diet-induced hyperglycemia and hyperinsulinemia. It should be noted, though, that commercially-sold varietals are not nearly as effective as wild bitter melon. One study observed the effects of bitter melon on diabetic rats. Specifically, they used an aqueous extract powder of fresh, unripe melons, and found that a dose of 20 mg per kilogram of body weight reduced fasting blood glucose levels by 48%. That rivals the effects of another popular synthetic medication, glibenclamide. And, compared to synthetic drugs like glibenclamide and metformin, the melon doesn’t show any kind of hepatotoxicity or nephrotoxicity (toxicity in the kidneys).

Part of the reason bitter melon is so effective is likely its effect on GLP-1 secretion. GLP-1 is glucagon-like peptide-1, a peptide released from what are called L-cells, which increase in density along the length of the intestines. It helps to raise insulin levels as a part of the incretin effect, a hormonal response that effects insulin secretion following oral glucose ingestion.

A study was done to examine the role of bitter melon extract in this process, nd found that through bitter taste receptors and/or a PLC β 2-signaling pathway, the melon stimulated GLP-1 release, which contributes, at least in part, to the antidiabetic activity of bitter melon through the incretin effect.

Now, before you think that by supplementing your diet with bitter melon, your insulin levels will get too high, it’s important to note that insulin levels that are regulated by GLP-1 are either reduced or, in some cases, completely absent in people suffering from diabetes. Considering that, and the fact that GLP-1 has an extremely short half-life due to rapid inactivation, it’s not likely that your insulin levels will become abnormally high by using the melon. In all likeliness, your insulin count will rise and settle at a relatively normal level. However, further studies will need to be performed to confirm this.

And there’s more.

Bitter melon, specifically a wild species called Momordica charantia Linn var. abbreviata ser., can also treat inflammation due to various diseases. Wild bitter melon and bitter melon extracts were used in a study to inhibit macrophage activity, which is a part of your natural immunological response to stress, disease, and tears in body tissues. The lipopolysaccharide (LPS)-stimulated macrophages that were targeted responded to both extracts, but especially to the wild variety of the melon, resulting in much-reduced inflammation.

As you may already know, insulin resistance is closely related to chronic inflammation induced by things like tumor necrosis factor-α (TNF- α), a compound that seeks out and destroys cancerous cells. But before jumping into the importance of TNF- α, you should memorize this chemical: triterpene 5β, 19-epoxy-25-methoxy-cucurbita-6.23-diene-3β, 19-diol – or, for short, EMCD. It’s purified from a wild species of bitter melon that was thought to activate AMP-activated protein kinase (AMPK), which itself is thought to repress TNF- α-induced inflammation.

When it was tested alongside a compound extracted from green tea that’s also reported to be anti-inflammatory, EMCD showed more obvious anti-inflammatory activity, but not by activating AMPK. It actually inhibited the activation of the IkB kinase, an important aspect of pro-inflammatory signaling, and thus, the melon extract mitigated inflammation tied to diabetes. Since inflammation is connected to shorter life spans and greater risk of conditions like cardiovascular diseases, you should definitely look into adding wild bitter melon to your diet or supplement cabinet as an anti-inflammatory strategy too.

Want more interesting reading on bitter melon extract? Check out these links:


The world of pharmacology is vast and complex, and full of drugs for every disease, infection and disorder you can think of. But the side effects that often go hand-in-hand with them almost make them not worth using. Next time you see a bottle of prescription medicine like metformin, look at the side effects label. It can be alarming (for example, some medicines for dealing with skin-level allergic reactions list freakin’ death as a possibility).

You shouldn’t have to run the risk of dying of a reaction to medication for something like diabetes or even skin irritation to attain better health and live longer. And that’s what makes natural dietary approaches and extracts as elegant as bitter melon so effective. 

Before jumping on the metformin bandwagon, I’d recommend you review the research above in full, and you consider doing exactly what I do – I follow all blood sugar stabilizing exercise practices I outline here and I restrict all carbohydrates until the end of the day – instead eating a wide variety of wild plants, high amounts of natural, healthy fats and moderated amounts of protein.

Finally, as a fantastic addition to the use of bitter melon extract via the capsule supplement I will highlight below, I am also a huge advocate of a daily shot of vinegar or a shot of vinegar before each meal (see the latest study released just last week entitled “Vinegar intake reduces body weight, body fat mass, and serum triglyceride levels in obese Japanese subjects.“) and also the equivalent of at least two teaspoons of Ceylon cinnamon per day (see just a smattering of the research on Ceylon cinnamon here). I occasionally also dig up Oregon grape root (which grows like a weed in my backyard) and steep the root in tea that I can sip on or use in smoothies, because Oregon grape root contains another potent blood sugar lowering agent that acts similarly to metformin: berberine (also available in supplement form should you not have a pocketknife, a teapot, and some Oregon grape root nearby).

Then, just before dinner, I pop two tiny capsules of Kion Lean, which contains both – you guessed it – rock lotus and wild bitter melon extract.

So what do the rock lotus and wild bitter melon in Kion Lean have in common that promote fat burning, liver health (and of course, anti-aging)?

The answer involves caloric restriction and insulin.

As you’ve just learned, two basic mechanisms have been shown to be successful in promoting longevity in higher organisms. The first mechanism lowers the levels of insulin and insulin-like growth factor 1 (IGF-1). The second mechanism restricts calories, which usually has, as one result, a lowering of circulating insulin levels. Rock lotus influences both of these mechanisms. According to a Jutendo Medical University of Japan clinical trial, rock lotus improves liver function and fatty liver. This action resembles that of compounds known to reduce insulin levels as an aspect of improved blood glucose control.

Wild bitter melon is similarly health promoting. For example, it has been found that extracts of the wild bitter melon activate cellular machinery to regulate energy production (technically AMPK-activated protein kinase) and the way that fats are handled by the liver. Activation of this metabolic pathway is important to aging. It is sometimes referred to as “exercise in a bottle” because activation of AMPK is an aspect of the benefits derived from exercise. The effect of an extract from the wild genotype of bitter melon called Glycostat® has proved to be more powerful than others on the market and much more consistent in producing positive results.

In short, rock lotus and Glycostat® work better in combination. Both promote better blood sugar control with less insulin. Both promote healthy blood pressure. Both support healthy liver function. And both mimic changes in cellular energy metabolism typical of caloric restriction.

In tandem, these two compounds work like gang-busters to regulate blood sugar levels after my evening carbohydrate-laden meal, and, as you’ve just learned, can set you on your path to becoming a centenarian yourself, all while enjoying phenomenal health without the nasty side effects of metformin. You can click here to try Kion Lean now, and I’d recommend using it exactly as I do – two capsules before any carbohydrate rich meal. It’s that simple.

Do you have questions, thoughts or feedback about metformin or my alternative of choice, bitter melon extract? Leave your comments below and I will reply. 

Ask Ben a Podcast Question

33 thoughts on “The Dark Side Of Metformin: A “Longevity Wonder Drug” That Promises to Extend Life For A Nickel A Pop.

  1. Ira Goodman MD says:

    What about trans dermal metformin to reduce gi side effects?

  2. Justin says:

    Thank you for the great article and your informative podcast. Have you revised your opinion on this since posting? Peter Attia seems to think that dosing is quite important for Metformin. He recommends very low doses taken irregularly (I believe once a week). I am curious to hear what you think of his latest podcast with Nir Barzilai.

  3. Laura F says:

    Would Kion Lean be helpful in managing hypoglycemia, or just hyperglycemia? I also have low blood pressure. Just want to make sure it would still be effective and not harmful in any way. Thank you!

    1. I am not a doctor and this is not to be taken, interpreted or construed as medical advice. Please talk with a licensed medical professional about this. These are just my own personal thoughts and not a prescription or a diagnosis or any form of health care whatsoever. Primarily hyperglycemia though.

  4. Tayler says:

    Hey Ben,

    Love the podcast. I’ve recently purchased a bottle of Kion lean. I take 2 capsules before dinner. I’ve noticed some nausea and diarrhea. Even threw up one time. Anyone else ever complain about this?

    Let me know your thoughts. Thank you!

    1. Tayler, I have not heard this before! Can you please email [email protected] so we can gather more information? Thank you!

  5. alicia says:

    Hello Ben,

    LOVE your podcasts. I learn so much. Question on the Kion Lean. I am a female, age 53, post menopause, in good shape, work out, but a little fat bulge collecting at the waistline line. I eat Paleo-ish….not super strict, but rarely sugar or carbs, or things that spike insulin. Trying to loose the little fat bulge. Since I don’t eat carb rich meals, would KION LEAN be of any value for me? It would be worth the money if it burned up fat. I have tried fat burners, but they are too strong and give me the jitters.. I would greatly appreciate you view on this. You men can burn up fat almost without trying! Lol. Thank you so much for your time. Keep up the great content rich podcasts.

    1. It is wonderful for the liver as as general tonic, and also as a digestif…so yes!

      1. alicia says:

        Thank you for your time! I plan to order a bottle soon then and see how it does with the fat burning. I also tried your protocol this morning for a light aerobic workout in a fasted state with some caffeine and then a cold shower for about 3 minutes. Is that long enough? You didn’t mention the length of time for the workout or the shower and I would like to know what you think for a female, 53.

  6. Pheobe says:

    As a 60 year old woman I battle blood sugar dysregulation every day but I manage it through diet and exercise. About 16 years ago an MD I used to consult scared me into trying Metformin. It almost killed me. One of the dirty little secrets they don’t tell you is that (in my opinion) the serious potential adverse reaction to Metformin that produces lactic acidosis is highly under-reported. I experienced the symptom referred to as Kussmaul’s breathing and when I reported this to my doctor he said that wasn’t possible as LA only occurs in .01% of patients. Well, I fired him right then and there and quit taking the Metformin. It took a couple of weeks to recover and after researching it thoroughly I found lots of data from hospital emergency rooms indicating to me that it is not as rare as they say. And, no, I am not in one of the categories that puts you at risk, such as hepatic insufficiency.

  7. Lisel Larson says:

    Metformin helps with weight loss – can MPX 100 do the same?


  8. Tim says:

    The MPX100 is waaaaaay over priced. Jarrow has a bitter melon product for $15; 1500 mg for two tabs.

  9. Tim says:

    The MPX100 is waaaaaay over priced. Jarrow has a bitter melon product for $15; 1500 mg for two tabs.

  10. Mike says:

    Nahhhh. Nice try with the flagrant non peer reviewed study blasted in your nonaquating vomit of information. Ughhh. Just take take berberine. Metformin too many side effects as any physician knows if treating more than 100 people. Plant based berberine at pharmaceutical grade as good if not better in reducing A1C. Same mg per meal just to make it easier. That’s the only go too instead of metformin. I love metrformins effects lot of truth above on stating the physiological relationship. I’ll give you that. But your Mellon ball or whatever. Nah bro. Berberine. Dr whiitterkrrs or any brand. I’ve seen the digits on all my patients why risk horrible diarrhea and lactic acid build up in the leg where you feel like you got Nancy cariganed evrrytime you go to bed. Ughh. From one exp intergrative Practitioners point of view who does this on the reg. Berberine. Same 500mg dose before a meal. And A1c money.

  11. Michael Karlin says:

    Hi Ben, can you comment on some of the side effects of taking bitter melon (some which seem can be serious) and what you do (if anything) to cycle / minimize such side effects? Thank you!

    1. There are zero side effects from moderate dosages. Folks in Okinawa have been consuming for thousands of years.

      I am not a doctor and this is not to be taken, interpreted or construed as medical advice. Please talk with a licensed medical professional about this. These are just my own personal thoughts and not a prescription or a diagnosis or any form of health care whatsoever.

  12. Brenda Nabi says:

    Hi Ben,

    I am pre-diabetic and went off Metformin because they thought I was allergic to it. I was not but remained off of it because of many articles such as yours holding me back. It is hard to know what to do.

  13. larry says:

    anyone diagnosed with t2d the goal is to lower bg so taking metformin is good but only then take additional steps….jack kruse stuff helped my dawn phen plus this article

  14. Celeste says:

    Would this Longevity Formula have an effect on high blood pressure, currently controlled by low salt diet and diuretic?

    1. No issues with high blood pressure for the fixes I’ve recommended in the article. There is a lot you can do for high blood pressure including:

      I am not a doctor and this is not to be taken, interpreted or construed as medical advice. Please talk with a licensed medical professional about this. These are just my own personal thoughts and not a prescription or a diagnosis or any form of health care whatsoever.

      If you prefer a more direct, customized approach, I'd be happy to help you via a personal one-on-one consult. Just go to and then choose a 20 or 60-minute consult, whichever you'd prefer. I can schedule ASAP after you get that. Additionally, if I'm "out of your price range" (yes, yes, I know I can be a spendy guy to access) I have a team of coaches I've personally trained who can help you here:…

  15. Dan S says:

    Well researched Ben but I do sense a bit of cognitive bias here. Metformin is essentially an herbal extract from the French lilac and like bitter melon was used as a traditional treatment in T2D. They both also work through similar mechanisms – AMPk activation and GLP-1 expression, similar to berberine. Bitter melon has also been shown to have a risk of hepatotoxicity in animal studies. I would guess that if bitter melon and even berberine were studied in humans as extensively as metformin then we would see a very similar side effect profile. As to the assertion regarding the pharmaceutical companies, they have no interest whatsoever in metformin, its off patent – they would not even fund the TAME study to look at healthspan effects for metformin. I am not saying that one substance is any better or worse than another but instead of looking at something as synthetic or natural, look at a systems based analysis, classify them as a body input and analyze outcome without the shroud of bias.

    1. Ben says:

      Metformin activates AMPK by creating a mitochondrial energy deficiency state much the same mechanism as does berberine. These two, therefore are alike. Bitter melon, to the contrary, has 70 or more active ingredients, some of which activate the liver and others that act directly on GLUT receptors and cell insulin receptors. This is not like metformin at all. Glykon itself has performed tests for cellular receptor activation using hepatocytes and cardiomyocytes and has two patent applications advancing through the USPTO related to these findings.

      The risk of hepatotoxicity from bitter melon in humans essentially in nonexistent. These so-called findings involved ripe fruit, which no one uses and which contains compounds not found in the immature fruit.

      Comments on bitter melon toxicity are akin to comments on chocolate toxicity based on dogs. Just as chocolate is toxic to canines, but not to humans, bitter melon is a birth control for male dogs, but obviously not for humans — witness China and India. Much population control from bitter melon there? As for the liver, PubMed lists 100 articles on the beneficial effects of bitter melon on the organ. Bitter melon is considered to be hepatoprotective. Typical of such articles:

      J Ethnopharmacol. 2006 Nov 24;108(2):236-42. Epub 2006 May 26.

      Some toxicological studies of Momordica charantia L. on albino rats in normal and alloxan diabetic rats.

  16. Frank says:

    I just started taking Berberine recently. Would it be okay to take Berberine and MPX100 together?

    1. YES, it is OK, but a bit redundant and not necessary to take both in my opinion.

  17. Angela Eckard says:

    Hi Ben,

    I’m a big fan and follower of your podcast! Do you know if MPX100 can be used while pregnant or breastfeeding in an otherwise normal person? Thank you!


    1. I am not a doctor and this is not to be taken, interpreted or construed as medical advice. Please talk with a licensed medical professional about this. These are just my own personal thoughts and not a prescription or a diagnosis or any form of health care whatsoever. But I have personally seen no contraindications for bitter melon or rock lotus during pregnancy.

  18. TJ says:

    Great article. Any recommendations for getting off of metformin? Can it be quit cold turkey or do I need to wean myself off?

    1. I am not a doctor and this is not to be taken, interpreted or construed as medical advice. Please talk with a licensed medical professional about this. These are just my own personal thoughts and not a prescription or a diagnosis or any form of health care whatsoever. But if it were me, I'd use some of the options I've written about above: bitter melon, ceylon cinnamon, vinegar, etc.

  19. bob says:

    Where did you find your health risk for diabetes on 23and me?…

    1. Export the results to a website like Promethease!

  20. excellent article Ben on all the issues around Metformin. I use it to help get folks off insulin and sulfonylureas but ultimate goal is heal the body and gut. Yes it can be done!

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