Diabetes, Longevity/Healthspan, Time Restricted Eating

Conflicting Standards? Statins and/or Metformin plus Exercise

Fix your diet, take these medications, and get to the gym and exercise. It is a VERY common message, but there is more nuance to apply as well in order to get the desired effect.

This is where the concept of optimization by alternating various states comes into play. What signals are exercise and these medications sending to the body, and do they jive?

As our logo indicates, described briefly here, and as our metrics tool highlights, spending time in either end of biological spectrums can be advantageous.

Metformin is a drug commonly prescribed for diabetes; a condition of excess calories typically in the form of carbohydrates and associated downstream consequences. In the state of diabetes, the signal being sent to the body is to be in feast and growth mode. Metformin works to put the breaks on this and by a variety of mechanisms (not fully yet agreed upon by experts), causes an influence by shifting to mechanisms associated with caloric deficits, meaning fasting and recovery mode – essentially the brakes metabolically. People interested in longevity are also now taking metformin to get a boost applying these metabolic breaks as there is copious amounts of information showing the benefit. This is expected with my theory on optimization, utilizing both ends of the spectrum; fasting and feeding – growth and recovery.

Enter exercise. Much of the benefit from exercise is stressing the body to be able to keep up metabolically with higher demands. How does this square with taking a medication analogous to metabolic breaks when your body is under stress?

In summary, our findings show that metformin inhibits the increase in skeletal muscle mitochondrial respiration after 12 weeks of moderate to vigorous aerobic exercise training (AET) despite no differences between placebo and metformin on mitochondrial protein synthesis. Metformin also attenuated the increase in whole‐body insulin sensitivity and cardiorespiratory fitness (CRF) after AET. However, metformin did not inhibit other AET improvements, including telomere elongation, fasting insulin, 24‐hr mean glucose, and body composition. Our findings suggest that combining two healthspan extending treatments, metformin and exercise, may interfere with the improvement in some parameters of physiological function and do not interact synergistically.

Metformin inhibits mitochondrial adaptations to aerobic exercise training in older adults – Konopka – – Aging Cell – Wiley Online Library1

An older 2012 study also found “in summary, exercise training increased insulin sensitivity in individuals with prediabetes. Adding metformin to training did not accentuate improvements in insulin sensitivity, and it may have blunted the full effects of training.”2 Easy to sort out huh?

Lets add statins to the mix

Statins are slightly less used than water, as they are prescribed for high cholesterol. Millions of prescriptions every year are issued. There is much debate over whether cholesterol is a causal factor necessitating medications such as statins, but that is a debate for another post (or many rather – it is fascinating but very complex). Regardless, what side of the debate one takes, there is no disagreement that cholesterol is a vital substance in the human body. Cholesterol is part of the cell membrane, arguably the most important part of the cell. Muscle cells have a high demand for cell membrane maintenance in times of exercise as much repair is often needed. If we encourage people to exercise and take statins, is there potential harm?

caution should be exercised in prescribing statins and exercise therapy (ET), particularly in high-risk groups. A cavalier approach to this combined therapy may unnecessarily expose individuals at risk to side effects, resulting in discontinuation of the treatment and subsequent increased risk for CVD events

The Interaction Between Statins and Exercise: Mechanisms and Strategies to Counter the Musculoskeletal Side Effects of This Combination Therapy3

Stefanie Seneff is a researcher I trust on all things cholesterol and glyphosate (Roundup), she is simply top notch. This is quote from a peice on her website:

Muscle contraction itself causes potassium loss, which further compounds the leak problem introduced by the statins, and the potassium loss due to contraction contributes significantly to muscle fatigue. Of course, muscles with insufficient cholesterol in their membranes lose potassium even faster. Statins make the muscles much more vulnerable to acidosis, both because their mitochondria are dysfunctional and because of an increase in ion leaks across their membranes. This is likely why athletes are more susceptible to muscle damage from statins (Meador and Huey, 2010, Sinzinger and O’Grady, 2004): their muscles are doubly challenged by both the statin drug and the exercise.

How Statins Really Work Explains Why They Don’t Really Work.4

This information is presented not to suggest an immediate stoppage of your medication (please don’t do that without talking to your doc!), but rather to add a little context to how they work and what opportunities we may have to coordinate the signals we send our body. Exercise and metformin/statins can be less beneficial than without. Part of how I look at optimization is amplifying the signals we send, by food, environment, etc, with additional strategies that work on the downstream pathways. In this case, instead of just advising a prediabetic to fix their diet (helpful!) and take these drugs, we can work together to implement a plan that uses both ends of the feeding/fasting and exercise/recovery spectrums. Tactics like time-restricted eating, carbohydrate scheduling/reduction, and exercise timing can be personalized. Metformin increases a cellular signal called AMPK, the same AMPK that is upregulated in fasting or calorically restricted times, and the same AMPK activated during exercise. AMPK is downregulated in highly fed states. Knowing this a program that implements exercise in a fasted state (AMPK signal x2) could be better than having a standard American breakfast cereal/oatmeal (AMPK-) with metformin and exercise (AMPK+). I tend to think it is a good idea to use either the gas or the brake…not both:

If you would like to evaluate plans such as this, please reach out.

  1. https://onlinelibrary.wiley.com/doi/full/10.1111/acel.12880
  2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3241331/
  3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3241331/
  4. https://people.csail.mit.edu/seneff/why_statins_dont_really_work.html

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