As many know, metformin is the number one prescription medication for type-2 diabetes. The patent for the name-brand of this patent medicine, Glucophage®, expired years ago and as a result generic-brand competition (metformin) brought this patent medicine’s price down so that it’s relatively inexpensive, especially when compared with nearly any other medication still covered by a patent.
Mainstream medical research has found other uses for this unnatural molecule, including (but not limited to) lipid, blood pressure, and insulin resistance lowering effects, anti-cancer effects, improvement of polycystic ovarian syndrome (PCOS), combatting Alzheimer’s disease, and extending lifespan in mice.
Surprising guests on the metformin bandwagon
Some proponents of natural therapies – including, surprisingly, two nationally and internationally circulated health magazines – have climbed on the metformin bandwagon, writing articles about the ‘health benefits’ of metformin, and even advocating that otherwise healthy people take this patent medicine every day as a preventive. They admit that there are known side effects, but write that these are few, and that the benefits outweigh the risks.
If there aren’t any natural treatment alternatives that are as effective, or more effective, than a patent medicine or other unnatural molecule – especially in serious or life-threatening situations – then the use of a patent medication of course makes sense. But when there are natural alternatives that work just as well or better, the rule is – and always should be – to ‘Copy Nature’.
Human bodies are formed from the molecules of planet Earth, and powered by the energies of this planet. Bodily health is best cared for with those same molecules and energies! Those are the ones likely to be the best ‘fit’, and to cause the least trouble. The longer unnatural molecules are used, the more likely they are to cause trouble. Using them for preventive reasons when we are healthy is especially foolish.
Tracing the botanical background of metformin
Metformin had its origin in botanical medicine, as do many modern patent medicines, which are deliberately altered to unnatural forms so they can be patented. It was initially derived from the plant Galega officinalis, or ‘goat’s rue’, also known as French lilac.1 One of the main constituents of these plants is guanidine, known from its use as a herbal medicine in medieval Europe. Besides treating plague, worms, St. Vitus Dance, and snake bites, folklore also suggests it was used in the treatment of blood sugar problems in animals.2 Metformin and other similarly derived patent medicines known as biguanides owe their origins to these plants.
Galega’s ability to affect high blood sugar was rediscovered in 1918, but the actual herb was too toxic for human use.3
The patent medicine metformin was first synthesized from it in the 1920s as a way of lowering blood sugar, but then abandoned in favour of research into the development of insulin and patent medicines that could be used to treat diabetes. The blood-sugar-lowering properties of metformin were again rediscovered in the 1940s and the first clinical trial was finally published in 1957.
Metformin has since become one of the most popular blood-sugar-lowering patent medicines in use 4 and is considered the ‘first-line’ patent medicine for treating type-2 diabetes. It’s also used to treat polycystic ovarian syndrome (PCOS), non-alcoholic fatty liver disease (NAFLD), and gestational diabetes, each of which involves elevations in blood sugar. While the way it works is still not well understood, in general it reduces the production of glucose by the liver, reducing blood sugar by 25% in up to 90% of its users. 5
But enough about the basics! Let’s move on to the various adverse effects of metformin use, and briefly mention the natural treatments that work as well – and often better – with fewer adverse effects.
The painful side effect that could kill you
One of the most serious adverse effects of metformin is lactic acidosis. This painful side effect is considered a rare but life-threatening complication of the therapy. Increased blood acidity and build-up of lactate occurs when cells receive too little oxygen, or become hypoxic. Because metformin is eliminated through the kidneys, it should never be used in patients with renal impairment, ironically a frequent complication from diabetes itself. Clinical practice guidelines recommend caution in using it for any patient with a glomerular filtration rate (GFR) of less than 60ml per minute and avoiding its use in any patient with a GFR that’s less than 30ml per minute. 6
In one Canadian study, the rate of occurrence of lactic acidosis was reported at nine cases per 100,000 person years for metformin exposure, 7 though some studies have reported it as high as 30 cases per 100,000 person years. Regardless of incidence, it has a high mortality rate: up to 50% of cases of lactic acidosis are fatal.8
Metformin associated lactic acidosis can even occur in patients who have no previous history of renal impairment, and in young people. While most reported cases occur in the elderly, cases involving young people without chronic kidney disease have been published.9 It’s also associated with overdose and there are some reports of suicide attempts using metformin.10 Lactic acidosis is a serious complication no matter the age of the victim and care should be taken to rule out any possible contraindications for the use of metformin.
Hormone havoc could be in your future
Research studies have reported metformin’s effects on a variety of hormones, including a reduction in testosterone in men and lowering of thyroid stimulating hormone (TSH) in both men and women.
In a small study involving 12 men taking 850mg of metformin twice daily for two weeks, researchers discovered a significant decrease in levels of total testosterone, free testosterone and 17-hydroxyprogesterone, as well as an increase in sex hormone binding globulin (SHBG) and DHEA-S. There weren’t any changes noted in fasting blood sugar or insulin levels, LH, FSH, blood pressure, or weight. Because the study length was limited to two weeks, researchers concluded that more study would be needed to determine the long-term effects of metformin
on testosterone and other androgen levels. 11
Similar androgen-lowering effects have been seen in women with PCOS, 12 a condition in which androgen levels rise for reasons as yet unknown.
TSH was lowered significantly in those who were hypothyroid and on metformin for at least a year. This effect occurred in hypothyroid individuals taking L-thyroxine (T4) with metformin, and hypothyroid individuals who took no L-thyroxine. It also happened to individuals with normal thyroid function who took this patent medicine. The researchers concluded that thyroid function should be re-evaluated in patients on metformin six to 12 months after therapy begins.13 Other studies have found similar results.14,15
But a recent study involving 828 individuals with normal thyroid function who were taking metformin also concluded that metformin did not affect their TSH levels.16 Since this study and prior studies partially conflict, it’s best to know your own thyroid status if you decide to use metformin.
And if you’re a man, check your testosterone and free testosterone levels before starting metformin – if you decide to do so – and again a few weeks later.
The metformin ‘belly bomb’ hits in 20-30% of cases
Digestive disturbances are the most commonly reported side effects of metformin, affecting 20-30% of those taking it. These side effects can be dose-related and reducing the dose often reduces symptoms. The symptoms most reported are gas, diarrhoea, stomach cramps, abdominal swelling, indigestion, and incomplete or infrequent bowel movements.17 Late onset diarrhoea is not an uncommon side effect, even after taking metformin without ill effect for many years.18
There are various theories about how metformin causes so much digestive disturbance. It’s been suggested that it may increase the intestinal secretion of serotonin, change the levels of ‘incretins’ (gastrointestinal hormones that reduce blood sugar by increasing insulin output) and their effect on blood-sugar metabolism, or that it contributes to malabsorption of bile acids.19 But none of these theories fully explain metformin’s adverse effects on digestion.
Look out for the low blood sugar link
Metformin can cause hypoglycaemia, though many people taking it aren’t aware of this potential side effect. Drops in blood sugar are more likely after intense exercise, missing a meal, or taking too high a dose.
Metformin is reported to be a rare cause of hypoglycaemia as compared to the sulfonylureas (other patent medications prescribed for type-2 diabetes), which are three times more likely to result in low blood sugar.20
Metformin can rob your body of critical vitamin B12
Metformin is known to reduce the absorption of vitamin B12 and folate acid in the gastrointestinal tract. Specifically, it’s thought to suppress ‘intrinsic factor’ the substance made in the stomach that’s necessary for vitamin B12 absorption in the ileum, the last part of the small intestine. One study looked at this process in 14 individuals who had taken metformin for three months. But when additional oral calcium supplementation was taken, the malabsorption was reversed.21
In a study of 152 diabetic outpatients on metformin, researchers looked at plasma homocysteine, vitamin B12, and folate levels. After six months researchers found a significant decline in vitamin B12 levels in the patients taking metformin as compared to a control group that was not taking this patent medicine. While there was no difference in folate levels, there was a variable effect on plasma homocysteine levels that depended on the amount and length of time metformin was taken. The researchers concluded that, for patients on long-term therapy with metformin, there’s a significant effect on the absorption of vitamin B12 and additional supplementation is warranted.22
Using data taken from adults over the age of 50 participating in the National Health and Nutrition Examination Survey (NHANES) from 1999-2006, researchers looked at the amount of vitamin B12 needed to restore diabetic patients on metformin to adequate levels. The amount of vitamin B12 contained in many standard multiple vitamins (6mcg) wasn’t adequate. Even worse, the study reported that while supplemental vitamin B12 did improve the vitamin B12 levels in diabetic patients not on metformin therapy, the levels didn’t improve in diabetic individuals taking this patent medicine.
The majority of individuals who were both not diabetic and not on metformin had an increase in vitamin B12 levels when taking a standard multivitamin. The researchers suggested higher amounts of vitamin B12 may be more effective in overcoming vitamin B12 deficiency in diabetic patients currently taking metformin.23
A subsequent randomized, placebo-controlled study found that the vitamin B12 deficiency not only persisted (was not transitory) but worsened over time. There was a small decrease in folate levels detected and the decline in both vitamin B12 and folate levels ultimately was associated with higher homocysteine levels.
The continuing and persistent decline in vitamin B12 levels in patients was a significant new finding in this study. Vitamin B12 deficiency has been associated with macrocytic anaemia, neuropathies and, most significantly, changes in mental function.24
Could metformin lead to heart failure?
Using metformin in patients with vascular conditions who are at risk for heart attack or heart failure is somewhat controversial even in ‘conventional’ medicine. While many recommend it as a safe therapy, there are also those who recommend caution. For example, it’s known that metformin has a damaging effect on vitamin B12, folate, and possibly homocysteine levels, and may increase the risk of heart attack in some patients.
Taking calcium blockers, using diuretics, and drinking alcohol can also affect the absorption and effect of metformin in the body.
Berberine matches or beats metformin’s performance
As I mentioned earlier, if there aren’t any natural treatment alternatives that work as well as (or better than) a patent medicine using a patent medication makes sense; especially if the condition is serious or life threatening. But otherwise it’s always best to ‘Copy Nature’. So what are the preferred natural alternatives to metformin? The botanical berberine stands out as the obvious number one alternative. Berberine is safer and equal to or superior to metformin in the following ways:
For treatment of type-2 diabetes, insulin resistance and the high lipid levels resulting from insulin resistance, berberine is equal (in blood sugar and insulin resistance regulating effect) or superior (in lowering high lipids) to metformin. (For details, see Nutrition & Healing, November 2010.)
Although allergy to anything at all is possible, including berberine, there’s little to no reported incidence of the long list of potential side effects of metformin when using berberine including headache, dizziness, tiredness, cardiovascular reactions, taste disturbances, acute infection of the nose, throat and sinuses (berberine is also a ‘natural antibiotic’), trouble breathing, flu-like symptoms, depletion of vitamin B12 and folate, anaemia caused by these vitamin depletions (‘megaloblastic anaemia’) or low blood sugar.
As noted above, lactic acidosis is a rare but sometimes life-threatening adverse effect of metformin. Berberine does not cause lactic acidosis!
Berberine beats in cholesterol control too
In treatment of polycystic ovarian syndrome, berberine was found superior to metformin in reducing total cholesterol, triglycerides, LDL-cholesterol, waist circumference, and waist-to-hip ratio. Berberine was again equal to metformin in improving fasting blood sugar and insulin resistance, as well as an increase in HDL cholesterol and SHBG levels. (For details, see Nutrition & Healing, February 2013.)
While metformin appears to significantly decrease total and free testosterone, berberine’s effects may be the opposite. One animal study reported that berberine increased testosterone output from testicular cells in oxygen-deprived circumstances. While doing this, berberine administration may also slow prostate cancer progression!
Berberine is a ‘5a-reductase inhibitor’, but a gentler natural one than patent medicines sold for the same effect. While tests done for Tahoma Clinic clients show that patent medicines routinely over-inhibit this enzyme, thus increasing risk of more aggressive prostate cancer (see the December 2012 Nutrition & Healing), so far not one man tested at Tahoma Clinic has had this effect with berberine. And berberine has not been reported to lower TSH levels.
Avoid digestive disturbances with ‘belly-friendly’ berberine
As noted in Nutrition & Healing, February 2013, 20-30% of those taking metformin report excess intestinal gas, diarrhoea, stomach cramps, abdominal swelling, indigestion, and incomplete or infrequent bowel movements.
Berberine LOWERS homocysteine levels
By contrast, when taken alone for blood-sugar regulation, berberine is associated with a very low incidence of digestive disorders. But when patent medicines for the treatment of blood sugar problems are taken together with berberine, the rate of digestive disturbance becomes significant (Nutrition & Healing, November 2010). The response of researchers has been to decrease the amount of berberine taken, but since berberine alone causes very few problems a more reasonable approach would be to remove the patent medicines instead!
Berberine has not been reported to cause low blood sugar, vitamin B12 or folate deficiency, raise homocysteine levels, or increase the risk of heart attacks. In fact, as noted in Nutrition & Healing February 2013, berberine actually lowers – not raises – homocysteine levels, and has been reported superior to placebo in improving heart function in individuals with congestive heart failure, as well as being useful for treating heart rhythm problems. (Metformin wasn’t tried, however, as noted above; while there’s disagreement, many think metformin actually worsens heart problems.)
Fight Alzheimer’s and repair nerve damage naturally
Some metformin enthusiasts point to a couple of relatively recently reported effects of metformin. Research has found that this patent medicine may have the potential to help prevent Alzheimer’s disease and treat cancer. But of course research tells us that berberine appears to be just as good, or even better, than metformin in these areas, too!
As reported in Nutrition & Healing, February 2013, berberine inhibits cholinesterase, a principal target of many current anti-Alzheimer’s patent medicines approved by the medical authorities. One animal study has already found that berberine suppresses brain cell’s inflammatory response to beta amyloid, a major factor in Alzheimer’s dementia.25
A second animal study – done with mice genetically engineered to develop human-style Alzheimer’s disease – found that berberine reduced both the damage caused by beta amyloid, and the amount of cognitive impairment.26 These animal studies were building on earlier research that had already shown berberine significantly reduces beta-amyloid production in cultured human brain cells.27
Other animal studies have found that berberine may help repair peripheral nerve damage. Animals with sciatic nerve damage were given berberine by injection; within a month, there was a noticeable regrowth of the damaged sciatic nerve.28 In the same publication, the researchers reported that berberine stimulated increased growth of dendrites, the very thin extensions branching out from the main body of a nerve cell which transmit information in and out. Metformin hasn’t been reported to have these effects!
As good as berberine may turn out to be against Alzheimer’s disease, there are at least three other natural therapies that may actually prevent Alzheimer’s disease in humans, and one that’s even been shown to reverse it in experimental animals!
Testosterone (for men) and oestrogen (for women), lithium, and curcumin (from turmeric) all significantly reduce Alzheimer’s disease risk. In addition, researchers at the University of California at Irvine have shown that niacinamide completely reverses the symptoms of early Alzheimer’s in experimental animals genetically engineered to develop the human variety of
Two natural substances could help keep cancer at bay
Metformin has been reported to have anti-cancer effects. And, as you may have already guessed, so has berberine! As you read in the Nutrition & Healing, February 2013 issue, berberine appears to inhibit breast cancer cell metastasis, kill the MCF-7 line of breast cancer cells, and inhibits the spread (metastasis) of melanoma cells from skin to many other organs, which is how melanoma usually becomes a killer. It also has effects against certain oral cancers, and inhibits the growth of prostate cancer cells.
Other research not included in that issue of Nutrition & Healing (but easily findable at ‘PubMed’ for those interested) has found that berberine is effective against bladder cancer cells, certain types of ovarian cancer cells, thyroid cancer cells, colon cancer cells, neuroblastoma and glioblastoma (brain cancers) cells, and cholangiocarcinoma (gallbladder-liver cancer) cells.
But berberine has competition as an up-and-coming natural and safe anti-cancer agent. Tocotrienols (the more active forms of the vitamin E family) have been shown to inhibit the growth of colon, skin, lung, liver, breast and prostate cancer cells (see Nutrition & Healing, January 2014 for details and footnotes). Tocotrienols may even slow the growth of pancreatic cancer! (See Nutrition & Healing, August 2013.)
Berberine ‘Bonus Points’
Berberine also protects against osteoporosis and is a major natural antibiotic, with activity against a wide spectrum of pathogenic (‘bad guy’) bacteria, including some strains of MRSA. Berberine has the ability to kill Helicobacter pylori, the bacterium known to cause gastric erosion, ulceration, and even stomach cancer. One group of researchers reported – using DNA testing of animal intestinal bacteria – that berberine “got rid of ‘bad guy’ bacteria, but didn’t interfere with the good guys”!
Berberine also can improve the platelet count in a very hard to treat disease, idiopathic cytopenic purpura (ITP). (Details – and footnotes – can be found in Nutrition & Healing, January 2014.) Metformin has not been reported to have any of these effects.
Metformin falls flat in the face of berberine
Although metformin is less dangerous than many patent medicines, it still has many more adverse effects than berberine, and its reach – both for treatment and prevention – isn’t as great. When we add in (for various preventive reasons mostly) testosterone for men, oestrogen for women, lithium (low dose, of course), turmeric, niacinamide, and the tocotrienols, I can’t think of a single reason to use metformin at all.
If you can think of a reason, please send me a note, along with footnotes! (I’m always happy to learn.) Your note – along with my thoughts – will be in a future newsletter.
As always, make sure to check with a doctor skilled and knowledgeable in natural medicine to make sure if any or all of the natural items mentioned above are a ‘fit’ for you!
Wishing you the best of health,
Dr. Jonathan V. Wright
Nutrition & Healing
Vol. 8, Issue 3 – March 2014
Full references and citations for this article are available in the downloadable PDF version of the monthly Nutrition and Healing issue in which this article appears.
Thanks to Dr. Ronald Steriti N.D. for locating nearly all of the research reports for this article, and to Dr. Lauren Russel, N.D. for organization of the data.