Metabolic inflexibility

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Update - October 2023

Since attending this conference, 10 years ago, at the date of this update, I have come to realise just how important it is for our bodies to run on ketones. This was a key point of the conference. Indeed, I now recommend the Paelo-Ketogenic diet for all my patients and have written a book and many webpages about this topic - see:

Reflections on Mitox Conference: 4 December, 2013

This conference, held at the John Radcliffe Hospital, Oxford, pertained to mitochondrial function in health and disease. To me the most interesting aspect of the conference was the idea of metabolic inflexibility. Clinically, I believe, this manifests itself where there is an inability to switch from metabolising carbohydrates to metabolising fats. This seems to be a feature of patients with CFS/ME who do not tolerate low carbohydrate diets. Clinically it appears they are unable to mobilise fat as a fuel source to the body. Of course, impaired fuel delivery will result in fatigue.

A paper presented by one of the speakers arose from experience in the Gulf War. Troops in the front line filled their ruck sacks with what they felt would be most important. Individual soldiers threw out their rations for ammunition. This meant many went for some days without food. One of the effects of this was severe mental fatigue and it was notable that most deaths from friendly fire resulted from soldiers in a state of starvation. Therefore, a team of scientists were commissioned by the military to look at foods that could sustain a soldier most efficiently in this situation. The budget for this piece of research was $10 million!

When fats are metabolised as a fuel they are first converted into ketones. So this team experimented by manufacturing beta hydroxybutyrate – a common ketone. This was then fed to trained athletes at the rate of 1.5 grams of beta hydroxybutyrate per kilogram of body weight per day, spread out in three separate meals. This was supplied in the form of drink which, we were told, tastes pretty disgusting. However, this had some interesting metabolic benefits.

On this ketone drink athletes were not hungry, and all lost weight. But despite this, their performance increased by 7%. This, for an elite athlete, is an astonishing improvement and will make the difference between an “also ran” and a “gold medal” performance! However, at a cost of £80 a day only a few could afford it.

Blood tests showed that glucose levels came down, as did triglycerides and cholesterol. Fatty liver was improved. Essentially, metabolic syndrome was reversed.

This study, therefore, shows there are clear benefits to be had when ketones are used as a fuel. The amount of ketones used in this study was a factor of ten higher than those available in the body when it switches into ketosis. Of course, the success of the Atkins diet can be explained by a switch into ketosis – people do not feel hungry, weight is lost. On the Atkins diet, metabolic syndrome is reversed.

What further helps makes this metabolic switch is exercise - I suspect just enough to switch into anaerobic metabolism is sufficient.

So whilst this was all very interesting, it still does not tell us how to ensure that CFS sufferers switch from carbohydrate to fat metabolism, especially when they can't exercise. However, what we do know is that practice makes perfect and those individuals who regularly consume a "low carb" diet more easily switch into fat burning than others. I suspect that modern diet, high in sugar and refined carbohydrate, means that people rarely make this metabolic switch and, therefore, it becomes increasingly difficult.

It may be that the 5:2 system of dieting helps us to exercise this metabolic mode. The idea here for the purposes of weight loss is to eat a constant amount of calories each day for 5 - 6 days in a week, for example 2000 calories daily, and then have one or two days of the week on a calorie intake reduced to a quarter of one’s usual – in the above example this would be 500 calories. If this is just done for a 24 hour window of time, then one continues to burn calories at the same rate and to achieve this one has to run down glycogen stores in the liver and switch into ketosis.

Other conditions which would trigger ketosis include thyrotoxicosis (so it is well worth getting thyroid function checked on the grounds that hypothyroidism would make it much more difficult to switch into ketosis) and fever (possibly some of the benefits of sauna'ing could be explained by this mechanism). I wonder if the business of getting hot, ie sauna'ing, facilitates this metabolic switch?

The above ties in with other clinical observations, such as that:

  • Diabetes is common in cases of mitochondrial disease;
  • Mitochondria function more efficiently when glucose levels are low;
  • High levels of glucose increase oxygen consumption but, paradoxically, levels of ATP fall. Incidentally humans generate 87.5 kg of ATP daily! This, of course, is achieved through efficient recycling.

Treatment of metabolic inflexibility

  1. Persist with the PK diet - see Diet, Detox and Die-off Reactions Expect to get worse for common problems and what to do about them.
  2. Avoid snacking - feeling hungry is a power stimulus to burn fat
  3. Check thyroid function - see Thyroid profile: free T3, free T4 and TSH
  4. Use niacinamide slow release 1500mgs daily - see Sales at Dr Myhill - Niacinamide B3 1500 mg 100 tablets
  5. Take chromium 2mgs daily for 2 months - see Sales at Dr Myhill - Chromium Picolinate 500mcg (100)
  6. Take berberine 500mgs three times daily - indeed berberine in these doses is of proven benefit in diabetes - see Efficacy of Berberine in Patients with Type 2 Diabetes
  7. Brief periods, 1-2 mins , of anaerobic exercise (to produce a lactic acid burn in muscles), repeated several times (interval training) will switch the body into fat burning (this is not for ME sufferers!). Furthermore it stays in a fat burning state for some hours subsequently.

For more detail on thyroid function issues, see

For more details on Diabetes, see:

For more detail on the right sort of exercise, see -

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