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Keto-flu, Ketogenesis, and Carb-tolerance: Part 1

A summary of our research: Ketogenic supplements

Low-carb diets and ketogenic diets are becoming increasingly popular for both lifestyle reasons and for the improvement of health and performance. However, there is little evidence for the superiority of keto- vs less restrictive low-carb approaches in the research. Greater carbohydrate restriction does provide additional benefits for some outcome measures like glucose, triglycerides (TG), and high-density lipoprotein cholesterol (HDL-c). There are also specific benefits from keto-diets and the levels of blood ketones they produce, including reduced inflammation, inhibited tumour growth (n some cancers), reduction in neurodegeneration, and increased metabolic flexibility.

But, despite the benefits and popularity of keto, there is surprisingly little consensus in the published research on what nutritional ketosis (NK) actually is!

There is also a complete lack of research on the time taken to achieve the common benchmark of nutritional ketosis ( ≥ 0.5 mmol/L  beta-hydroxybutyrate (BOHB)) and on the symptoms of carbohydrate-withdrawal commonly described in mainstream media as ‘keto-flu’. Dietary supplements and methods to improve ketonaemia (blood ketone levels), time-to-NK, and symptoms of carbohydrate withdrawal and mood during keto-induction are similarly not well understood.

Throughout my masters and doctoral research, my team and I provided, for the first time, a synthesis of research related to the time it takes for people to achieve ketosis and highlighted that there were no studies that had specifically evaluated adverse effects specifically during keto-induction.


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Key Findings:

  • Medium chain triglycerides (MCTs) resulted in fewer symptoms of Keto-flu when compared to control oil.
  • The amount of carbohydrate restriction only had a trivial effect on increasing symptoms of keto-flu.

Which supplements are ketogenic?

Our review on the use of supplements to initiate ketosis showed that there is a clear ketogenic effect of supplementing with medium-chain triglycerides (MCTs) and possibly an even greater effect resulting from shorter-chain fatty acids like butyric acid, although this is by no means proven.  However, the ketogenic effect of other supplements was unclear. It was also clear that although not increasing ketogenesis directly (i.e. the internal creation of ketones in the body), there was a clear and substantial effect of exogenous ketone supplements on ketone levels and that any inhibition of internal ketone production by exogenous ketones, is minimal.1

Do MCTs result in faster ketosis with fewer side-effects?

To understand the effect of increased ketonaemia on the time take to achieve ketosis and on symptoms of carbohydrate withdrawal, and mood, we performed a randomised controlled trial comparing the use of MCTs in a ‘classic’ ketogenic diet providing at least 80% calories from fat to a control diet (with the same amounts of all macronutrients) but supplemented with a long-chain dominant fat (sunflower oil) as a control.2

MCT supplementation resulted in higher BOHB at all time-points, and faster time-to-ketosis, but these results failed to reach statistical significance.

BOHB in a keto-diet with MCT or Sunflower Oil

Symptoms of keto-flu overall were greater in the control group, except for abdominal pain, which occurred with greater frequency and severity in the MCT-supplemented diet (a known side-effect of high-dose MCT supplementation.

Note that in this study we used 30 ml of MCT [2 x Tbsp.] three times per day!

There was also a likely benefit on symptoms of keto-flu from taking MCT but the effect on mood was unclear.

Symptoms of keto-induction (Keto-Flu) in a keto-diet using either MCT or Sunflower Oil

References

1.          Balasse EO, Neef MA. Inhibition of ketogenesis by ketone bodies in fasting humans. Metabolism. 1975;24(9):999-1007.

2.          Harvey CJdC, Schofield GM, Williden M, McQuillan JA. The effect of medium chain triglycerides on time to nutritional ketosis and symptoms of keto-induction in healthy adults: a randomised controlled clinical trial. J Nutr Metab. 2018;2018:9.

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