The effect of a ketogenic diet on the exercise induced immune response

Athletes are much concerned with their diets: good nutrition can*t make a bad
athlete good, but poor nutrition can make a good athlete worse. Therefore,
sports performance and nutrition are inseparably linked [1]. Recently, more and
more athletes are gaining interest in varying the amount of carbohydrates in
their diets. Concepts, such as "Train Low * Compete High" and a ketogenic diet
are used by both recreational and professional athletes. This concept means
training with a low carbohydrate status and competing with a high carbohydrate
status [2]. For athletes this means that they start a workout with a low
carbohydrate status. The idea is that this improves fat burning [3], and that
athletes are able to postpone glycogen use during an extensive exercise bout.
Athletes can get a low carbohydrate status by training in the evening, then no
dinner or a dinner with hardly any carbohydrates, followed by a training the
next morning, without breakfast. Another way to achieve a low carbohydrate
status, is to follow a (ketogenic) diet very low in carbohydrates during a
number of weeks.
The effect of a low carbohydrate diet on exercise performance is known [4]. A
low carbohydrate diet does not result in peak performance at high intensity,
compared to a high carbohydrate diet. However, a low carbohydrate diet does not
affect moderate intensity exercise performance [5].
Following a low carbohydrate diet could result in temporarily ketogenesis, in
other words, the athlete will use ketone bodies (Acetoacetate, acetone and *-
hydroxybutyrate) for the production of energy. Adapting to a low carbohydrate,
high fat diet takes 5 days [6], while adapting to a ketogenic diet takes two
weeks [7].
There are indications that ketones can have a positive effect on the immune
response. For example, *-hydroxybutyrate inhibits the activity of the NLRP3
inflammasome, causing it to release less cytokines [8]. A ketogenic diet is
known to have positive effects on persons with certain skin disorders and
epileptic attacks [9]. However, the effects of a ketogenic diet on the immune
response after exercise are unknown. In sports, a ketogenic diet can possibly
suppress the exercise induced immune response.
An immune response occurs during and after exercise in an athletes* body. This
immune response results in adaptation of the athletes* body to training, which
makes the athlete better and stronger, but it also results in a vulnerable time
frame directly after exercise, in which an athlete is more susceptible to
infection and diseases [10]. Nutrition could possibly influence this exercise
induced immune response.
But whether a low carbohydrate diet really leads to an altered immune response
after exercise has never been studied, even though many athletes follow such a
diet for shorter or longer periods of time. When athletes follow such a diet
for a longer period, they can really switch to ketogeneses, when they follow
such a diet for a shorter period/a few days, this diet would probably cause a
metabolic stress factor, which can influence the exercise induced immune
response as well [11].
Therefore, the aim of this research is to examine the influence of a ketogenic
diet on the exercise induced immune response.


1. Jeukendrup, A. and M. Gleeson, Sport nutrition: an introduction to energy
production and performance. 2010: Human Kinetics.
2. Burke, L.M., Fueling strategies to optimize performance: training high or
training low? Scand J Med Sci Sports, 2010. 20 Suppl 2: p. 48-58.
3. Cox, P.J., et al., Nutritional Ketosis Alters Fuel Preference and Thereby
Endurance Performance in Athletes. Cell Metab, 2016. 24(2): p. 256-68.
4. Burke, L.M., Re-Examining High-Fat Diets for Sports Performance: Did We Call
the 'Nail in the Coffin' Too Soon? Sports Med, 2015. 45 Suppl 1: p. S33-49.
5. Volek, J.S., T. Noakes, and S.D. Phinney, Rethinking fat as a fuel for
endurance exercise. Eur J Sport Sci, 2015. 15(1): p. 13-20.
6. Goedecke, J.H., et al., Metabolic adaptations to a high-fat diet in
endurance cyclists. Metabolism, 1999. 48(12): p. 1509-17.
7. Phinney, S.D., Ketogenic diets and physical performance. Nutr Metab (Lond),
2004. 1(1): p. 2.
8. Youm, Y.H., et al., The ketone metabolite beta-hydroxybutyrate blocks NLRP3
inflammasome-mediated inflammatory disease. Nat Med, 2015. 21(3): p. 263-9.
9. McNally, M.A. and A.L. Hartman, Ketone bodies in epilepsy. J Neurochem,
2012. 121(1): p. 28-35.
10. Nieman, D.C., Immune response to heavy exertion. J Appl Physiol (1985),
1997. 82(5): p. 1385-94.
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function. J Sports Sci, 2004. 22(1): p. 115-25.

To examine whether a short or longer period on a ketogenic diet leads to an
altered immune response after exercise.

A cross-over intervention study, with a total duration of 6 weeks. An athlete
follows a high, or low carbohydrate (ketogenic) diet. After 2 days a test day
takes place where the athlete performs an exercise test of 90 minutes, and
blood samples are taken at different time points. After that, the athlete still
follows the diet for another 12 days, after which he/she comes back again for
another identical test day. Then a 2 weeks wash-out period. After that, the
athlete follows the same protocol but then with the low (ketogenic), or high
carbohydrate diet.

The intervention consists of a custom diet that is followed for 2 weeks. After
2 days on the diet, a test day takes place and after 2 weeks on the diet
another test day takes place. The diet is low, or high in carbohydrates. With
low meaning under 10 En% from carbohydrates, and with high meaning more than 50
En% from carbohydrates. The protein intake will be set at ~15 En% in both
diets.

Burden: time investment (~31hours), following the prescribed diet (2x two
weeks), performing exercise tests (VO2max 1x and 90min exercise test 2x),
Blood, saliva, urinary and faeces samples.

Risks: Exercise tests will be intensive, however, athletes are used to that.
The diet could cause some discomfort. And blood withdrawals can lead to bruises
and discomfort (afterwards).