Exercise before Fasting Kick-starts Ketosis

This post originally appeared as my weekly newsletter, which you can sign up for HERE.

Fasting for weight loss is extremely popular. However, there are many other benefits of fasting that are independent of losing fat, including the proposed effects on healthspan and lifespan. While a lot of data have been gathered in animal models, there is good evidence that fasting activates several “pro-longevity” pathways in the body which make our cells more resilient, clear out damaged proteins, and improve overall metabolic health. 

Many benefits of fasting may also be related to the production of ketones during fasting. Ketones are formed by our liver when the body is in a fat-burning state and insulin is low, and can be used by our brain and other tissues as an “alternative” energy source. Ketones have also been shown to act as signaling molecules, activating similar pathways as fasting. For this reason, there is a growing literature on using the ketogenic diet, fasting, and exogenous ketones (all of which elevate levels of blood ketones) to leverage the metabolic and (potential) lifespan-enhancing benefits.

Fasting is a great way to elevate blood ketones, as is a ketogenic diet. However, exercise is also a potent activator of ketosis and perhaps better and more effective than fasting. This is because exercise rapidly depletes liver glycogen and therefore, “switches” the body to a fat-burning state which continues into the post-exercise window — something known as “post-exercise ketosis.”

The question then becomes whether stacking interventions could be a more effective way to promote and sustain ketosis?

A new study published in the journal Medicine and Science in Sports and Exercise (MSSE) was interested in this question. Specifically, the goal of this study was to determine how a 36-hour fast influences the production of beta-hydroxybutyrate (BHB, which is categorized as a ketone) and how performing intense exercise at the beginning of this fast would influence ketone production.


Brief study methods

20 young individuals took part in this study (11 men and 9 women with an average age of 26.) In a randomized order, participants complete two different arms of the study:

– Fasting only intervention: 36-hour water-only fast

– Fasting + exercise intervention: 36-hour water-only fast with a bout of high-intensity treadmill exercise at the beginning of the fast

It is worth noting the type of exercise performed in this study, which was intense treadmill running at 70% of participant’s heart rate reserve until they had burned about ~600 calories — the amount contained in the pre-fast standardized meal provided to all participants. The exercise was designed to burn glucose/glycogen as the primary fuel source.

At the start of the fast (hour 0), 12, 24, and 36 hours, levels of blood BHB, insulin, and glucagon were measured, as were psychological measures such as hunger, thirst, stomach discomfort, and mood.

Results

– The exercise + fasting condition resulted in a larger area-under-the-curve (AUC) for BHB — indicating a greater total exposure to elevated ketones throughout the fast

– The exercise + fasting condition expedited the time taken to achieve ketosis by ~3.5 hours (participants entered ketosis quicker when exercising before the fast)

– No differences in insulin AUC were observed between conditions, but exercise + fasting resulted in a larger glucagon AUC

– Hunger, thirst, and stomach discomfort were similar for both conditions

– Participants reported feeling more “depressed” during the non-exercise condition vs. the exercise + fasting condition


The first thing to note about these findings is the general observation of how long into a fast it takes to achieve clinical levels of ketosis — which are defined as levels of BHB >0.5 millimolar (mM.) In this study, on average, it took participants ~21 hours to reach this threshold. For those interested in how fasting affects ketones, this data is useful because it informs how long one might need to fast to boost blood ketones to this level or above. Granted, one’s usual diet and physical activity, as well as many other factors, will drastically influence the magnitude and timing of ketone production in the body.

In the exercise condition, it took only ~17.5 hours to reach a BHB level of 0.5mM, and BHB levels were 43% greater throughout the entire fast compared to a fast without exercise. If you want to put your body into ketosis quicker, it seems like exercising before you start your fast is the way to do it. Furthermore, it doesn’t seem like exercise elevates hunger levels or mood any more than a 36-hour fast with no exercise and may reduce your “depressive” symptoms during the fast (thanks, endorphins!)

There are many ways to build upon this study and several questions that remain. For instance, how does exercise placed at different time points during a fast affect ketone levels? Would the results be the same if one exercised midway through the fast or rather, ended a 36-hour fast with a bout of exercise?

Many protocols can work for achieving ketosis and trying to enhance the metabolic adaptations of fasting and exercise. My routine typically lends itself to ending my fast (or rather my bout of time-restricted feeding) with exercise. This will usually be about 10-12 hours after my last meal (dinner). Then, I’ll continue to fast for about 2-3 hours before eating breakfast/lunch. While I’m not sure what my levels of ketones are during this protocol, measuring is something I’ve considered and may do in the near future as an n=1 experiment.

Thanks for reading.

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