Satiating Effect of a Ketogenic Diet and Its Impact on Muscle Improvement and Oxidation State in Multiple Sclerosis Patients

Abstract

Background: It was previously established that Multiple sclerosis (MS) generates energy alterations at the mitochondrial level related to the loss of muscle mass. Ketone bodies, mainly beta-hydroxybutyrate (BHB), re-establish this energy alteration causing satiety, changes in body composition and a decrease in hormone-dependant hunger, such as ghrelin. The aim of this study was to establish possible improvements in body composition and the level of oxidation in patients with MS, by means of the satiating effect of a ketogenic diet.

Methods: A pilot study was carried out with 27 MS patients who were given a Mediterranean isocaloric and ketogenic diet for 4 months. Anthropometric measurements, as well as satiety and hunger perception (VAS scale), were taken. In addition, BHB and paraoxonase 1 (PON1), as an oxidation marker, were measured by spectrophotometric automated assays, and ghrelin was determined by an enzyme immunoassay in the serum. All measurements were taken before and after the intervention.

Results: A significant increase in satiety perception at lunch and dinner and of BHB in the blood was obtained. Hunger perception decreased significantly at lunch and dinner with similar levels of ghrelin. In addition, an important increase in lean mass and PON1 was observed. To our knowledge, this is the first study addressing improvements in body composition, oxidation state and metabolism in MS patients, based on the satiating effect of a Mediterranean isocaloric diet.

Conclusion: A ketogenic diet increases lean mass and decreases inflammation and oxidation possibly as a consequence of an increase in satiety and decrease in hunger in MS patients.

Keywords: ghrelin; ketogenic diet; multiple sclerosis; paraoxonase 1; satiety; β-hydroxybutyrate.

Figure 1

Changes in muscle and fat percentage and PON1 (paraoxonase 1) levels in serum. (A) N = 27; Body composition measurements were taken using the Faulkner method; Wilcoxon signed-rank test showed a significant increase in muscle mass (p = 0.003). (B) N = 27; Body composition measurements were taken using the Faulkner method; Wilcoxon signed-rank test showed a significant decrease in fat mass (p = 0.000). (C) N = 27; The PON1 activity was measured by using 4-Nitrophenyl acetate; Wilcoxon signed-rank test showed a significant increase in PON1 (p = 0.000).

Figure 2

The effects of the ketogenic diet on different organs. (A) The beta-hydroxybutyrate (BHB) ketone body changes the way energy is used in the brain, increasing medium-chain triglycerides (MCT)1 and MCT4 in the astrocytes, which are part of the blood-brain barrier (BBB) and decreasing glucose transporter 1 (GLUT1) of the blood vessels of the BBB, being responsible for transporting ketone bodies and glucose, respectively, to the Central Nervous System (CNS). Ketone bodies have anabolic and anti-catabolic activity in the skeletal muscle. Finally, ghrelin joins its specific receptor (GHS1a) within the CNS, activating the Y neuropeptide. (B) Possible effects of the ketogenic diet on different organs y molecules (PON1). After the intervention, an increase in BHB production was observed. In addition, the increased perception of satiety during lunch and dinner raises the possibility that this increase will be greater in these temporal intervals (2:00 p.m and 9.30 p.m) depending on the time of administration of coconut oil. Regarding ghrelin, fasting levels are maintained as before the start of the intervention. However, depending on the interaction with the production of ketonic bodies already described, the production could decrease coinciding with the increase of BHB (2:00 p.m and 9.30 p.m). These two associated processes may explain the increase in muscle and the decrease in fat. Both aspects would be related to a better metabolic profile, evidenced by the higher production of PON1 in the liver as an anti-inflammatory marker.