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Metformin Counteracts Benefits of Exercise

Ice baths stimulate mitochondrial repair, restore insulin sensitivity, & reverse Type 2 diabetes


Man holding continuous glucose monitor to camera
When Jason Kurchner stopped taking metformin, his insulin sensitivity improved and his blood glucose readings dropped down into the normal range.

Summary

  • Although metformin is a first-line treatment for Type 2 diabetes, patients who exercise, ice bath, and eat a low-glycemic index diet may fail to improve.

  • Clinical studies show that metformin counteracts the mitochondrial benefits of exercise.

  • Only after quitting metformin did Jason Kurchner's continuous glucose monitor register blood glucose readings that were in the normal range for an entire day.


Metformin Hurts Mitochondria


Metformin Blunts Mitochondrial Benefits of Exercise

A recent study estimated the cost of diabetes at almost $420 billion/year in the United States in 2022 (Parker et al. 2024). The average cost per patient in direct medical care for diabetes is more than $1000/month, and one of the most popular therapies is a drug called metformin. More than 90 million prescriptions for metformin are written every year, generating nearly $2 billion/yr in drug sales for its manufacturers.


It is no wonder that metformin has become so popular, given that clinical trials show efficacy for lowering blood glucose levels (Horakova et al. 2019). However, the mechanisms by which metformin acts remain uncertain, despite years of intensive research. According to a book quoted by the NIH, "metformin effectively lowers blood glucose levels by decreasing glucose production in the liver, diminishing intestinal absorption, and enhancing insulin sensitivity" (Corcoran & Jacobs 2023).


All of these mechanisms may be true, but they have nothing to do with the underlying cause of Type 2 diabetes -- mitochondrial injury. That is, metformin will mask the symptoms of Type 2 diabetes by interrupting mechanisms of glucose absorption and interfering with neoglucogenesis, but until recently few investigators bothered to ask "What effect metformin might have on mitochondria?"


That lack of curiosity in research is a serious problem, because according to a recent clinical study, metformin overcomes insulin resistance not by benefiting the mitochondria, but at their expense. A team of at Colorado State University in Fort Collins CO recruited more than two dozen participants at risk of Type 2 diabetes to study the effects of exercise and metformin in combination. Every participant was enrolled in a program of aerobioc exercise, but only half got metformin. The other half got a placebo.


After 12 weeks, the team discovered that metformin reverses the mitochondrial benefits of the exercise (Konopka 2018). The participants taking metformin experienced less improvement in cardiorespiratory fitness and whole‐body insulin sensitivity. Moreover, the group taking metformin experienced less improvement in mitochondrial respiration, compared to controls.


The results of the Colorado study agree with those of earlier studies that showed "adding metformin (to an exercise program) blunted the full effect of exercise training" (Malin et al. 2012) and that "the combination of short-term metformin treatment and an acute bout of exercise does not enhance insulin sensitivity" (Sharoff et al. 2010).


Addition of metformin (to a program of exercise) may attenuate the well-documented effects of exercise alone. - Sharoff et al. (2010)

Mitochondrial Therapy

In Ice Baths Mitochondrial Therapy I wrote about the beneficial effects of cold plunge therap on mitochondrial health, and the implications that may have for extending lifespan (i.e., reversing biological age). Like exercise, cold is a hormetic stressor -- i.e., a stress that temporarily impairs function, but stimulates the body to respond by becoming stronger.


Cold is to mitochondria like weightlifting is muscles. For a day or two after a strenuous workout, muscles will be sore and feel weak. That stress stimulates the body to build stronger muscles, in preparation for the next workout.


During cold exposure, the mitochondria must work extra hard to power thermogenesis. That load can produce reactive oxygen species that signal two therapeutic processes:


  1. mitophagy, which is the process by which your cells identify and destroy defective mitochondria, and

  2. mitobiogenesis, which is the process by which your cells make new mitochondria


After an heavy session of cold exposure, mitochondrial recovery can take several days, after which the mitochondria come back stronger. For example, when researchers subjected mice to 72 hours of cold air exposure, they found that the cold resulted "both degradation of mature mitochondria by mitophagy and synthesis of new mitochondria that led to a net increase in the total amount of mitochondria" (Yau et al. 2021).


The mitochondrial benefits can be so powerful that Cold Reverses Type 2 Diabetes. For example, author AJ Kay was diagnosed with full-on, uncontrolled Type 2 diabetes when her HbA1c was measured above 7%. She wrote about her reversal without metformin and without insulin in How Ketosis and Ice Baths Reversed My Type 2 Diabetes


What these studies reveal is that neither metformin or insulin can reverse the mitochondrial damage that is underlying cause of Type 2 diabetes. However, changes in diet (e.g., elimination of seed oils and reduction of carbohydrates), improved light hygiene (e.g., darker nights, lighter days), exercise, and cold plunge can restore mitochondrial health -- without either drug.


Type 2 Diabetes Reversed After Quitting Metformin

Jason Kurchner is a Morozko customer and a friend in his late 60's who has been very successful in business, only to discover that he'd let his health suffer. Eventually, I think every successful business person come to the realization that their own health is critical to both their professional and personal success. For Kurchner, a Type 2 diabetes diagnosis was part of that realization.


He resolved to increase his exercise, to eliminate processed foods from his diet, to reduce his consumption of high glycemic carbohydrates, to ice bath every day, and of course he consulted with his doctor so that he could embark on his metabolic restoration journey under the supervision of a qualified physician.


Like most medical doctors treating patients who present with symptoms of insulin resistance, Kurchner's doctor prescribed metformin, which is often the first line of treatment for hyperglycemia (high blood sugar). However, there is no medical school training that teaches doctors to avoid metformin for their patients who are committed to exercise. Few physicians have the time to keep up with the latest research findings, much less figure out how to translate those findings into practice.


So when Kurchner's blood glucose readings failed to improve in response to metformin, in exactly the way that this research would have predicted instead of discontinuing his dosage altogether, Kurcher's doctor doubled the dose.


But more metformin doesn't work.

It wasn't until I interviewed Ben Bikman, PhD that I realized my friend shouldn't be taking metformin at all. Bikman was the first person to point me towards the studies that show how metformin works in opposition to exercise, keeping the poor patient in a chronic state of mitochondrial injury despite his best efforts.


When I told Kurchner about my call with Bikman, he decided to go against his doctor's advice and quit taking the metforming immediately.


Continuous glucose monitor screenshot showing normal blood glucose
Jason Kurchner's continuous glucose monitor registered 94 mg/dL in the evening after he ate dinner -- his first blood glucose reading under 100 mg/dL ever.

He got better.


Less than six weeks later, he sent me a screenshot of his first blood glucose reading ever under 100 mg/dL. And what's more, he wasn't even fasting when he posted it.


You can see in his daily data that some of his blood glucose readings are still too high. For example, in the afternoon he almost reaches 140 mg/dL, which is in a range that could still be considered "pre-diabetic," depending on the context. However, there is nothing about his readings on this day that suggests he still meets the diagnostic criteria of Type 2 diabetes.


At the rate Kurchner is going, his doctor will some be able to pronounce him miraculously "cured" or what the doctor once thought was a chronic, degenerative disease requiring a lifetime of medication.


Medicine vs Health

You might think that if there were proven antidiabetic therapies available without drugs, then clinicians would no doubt be prescribing them. I've found that is rarely the case.


Clinical practices change too slowly, because the medical doctorate is not a research degree. It's a professional doctorate, like lawyers earn, and the continuing education industry for medical professionals is dominated by the pharmaceutical companies that profit from "educating" doctors about new drugs. That is, the $2 billion/year metformin industry emerged because the drug companies have the budget to market the new drug to clinicians who do not have the time (and in most cases the skills) to educate themselves.

 

Medical doctors would be wise to attend to the advantages of cold therapy for type 2 diabetes management, even if healing these patients would damage drug company sales. 

  

Most doctors and medical guidelines will advise Type 2 diabetic patients to make changes to their diet and patterns of exercise, knowing that their patients are unlikely to comply. What Kurchner's experience shows us is that even when patients make all the prescribed lifestyle changes, the drugs that physicians are taught to prescribe can undo all the benefits of those changes -- thus keeping the patient dependent on pharmaceutical purchases for the rest of their lives and wondering why everything their working so hard at isn't working.


References 

  • Corcoran C, Jacobs TF. Metformin. StatPearls Publishing; 2024. https://www.ncbi.nlm.nih.gov/books/NBK518983/

  • Konopka AR, Laurin JL, Schoenberg HM, et al. Metformin inhibits mitochondrial adaptations to aerobic exercise training in older adults. Aging Cell. 2019; 18:e12880.

  • Horakova O, Kroupova P, Bardova K, Buresova J, Janovska P, Kopecky J, Rossmeisl M. Metformin acutely lowers blood glucose levels by inhibition of intestinal glucose transport. Scientific reports. 2019 Apr 16;9(1):6156.

  • Malin SK, Gerber R, Chipkin SR, et al. Independent and combined effects of exercise training and metformin on insulin sensitivity in individuals with prediabetes. Diabetes Care. 2012 Jan;35(1):131-6. doi: 10.2337/dc11-0925.

  • Parker ED, Lin J, Mahoney T, Ume N, Yang G, Gabbay RA, ElSayed NA, Bannuru RR. Economic costs of diabetes in the US in 2022. Diabetes Care. 2024 Jan 1;47(1):26-43.

  • Sharoff CG, Hagobian TA, Malin SK, et al. Combining short-term metformin treatment and one bout of exercise does not increase insulin action in insulin-resistant individuals. Am J Physiol Endocrinol Metab. 2010 Apr;298(4): E815-23. doi: 10.1152/ajpendo.00517.2009.

  • Yau WW, Wong KA, Zhou J, Thimmukonda NK, Wu Y, Bay BH, Singh BK, Yen PM. Chronic cold exposure induces autophagy to promote fatty acid oxidation, mitochondrial turnover, and thermogenesis in brown adipose tissue. IScience. 2021 May 21;24(5).

 

About the Author

Thomas P Seager, PhD is an Associate Professor in the School of Sustainable Engineering at Arizona State University. Seager co-founded the Morozko Forge ice bath company and is an expert in the use of ice baths for building metabolic and psychological resilience.



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