Ketogenic diets and pain

Abstract

Ketogenic diets are well established as a successful anticonvulsant therapy. Based on overlap between mechanisms postulated to underlie pain and inflammation, and mechanisms postulated to underlie therapeutic effects of ketogenic diets, recent studies have explored the ability for ketogenic diets to reduce pain. Here we review clinical and basic research thus far exploring the impact of a ketogenic diet on thermal pain, inflammation, and neuropathic pain.

Keywords: Taxol; chronic constriction injury; glucose; hypoalgesia; inflammation; ketones; metabolismc; neuropathic pain.

Figure 1

Temperature-response curves from hotplate tests in rats on two differing ketogenic diets. Top X-axes indicate plate temperature, those on the bottom indicate days on diet. A) Rats on control diet or a 6.6:1 ketogenic diet. B) Rats on control diet or a 3.0:1 ketogenic diet. Both diets produced significant hypoalgesia. Number of subjects was 18-20. *p<0.05 **p<0.01, ***p<0.001 versus control diet. Adapted from published work.

Figure 2

Elevated ketones and reduced glucose without thermal hypoalgesia. Rats were fed on a 6.6:1 ketogenic diet for one day before daily hotplate testing commenced (A). Separate groups of rats were used for sampling of tail whole blood (B, C). *p<0.05, ***p<0.001 versus control diet. Adapted from published work.

Figure 3

Thermal hypoalgesia without reduced glucose. Rats were on a 3.0:1 ketogenic diet for 70 days before daily hotplate testing (A). Separate groups of rats were used for sampling of tail whole blood (B,C). #p=0.055, *p<0.05, **p<0.01, ***p<0.001 versus control diet. Adapted from published work.

Figure 4

Effects of a 6.6:1 ketogenic diet on experimental inflammation in juvenile rats. Left: schematic of the subcutaneous injection of complete Freunds’ adjuvant between the tori of a rat hindpaw. Middle: hindpaw swelling was significantly reduced in animals on a ketogenic diet. Right: plasma extravasation was significantly reduced in animals on a ketogenic diet. Adapted from published studies.

Figure 5

A ketogenic diet has little effect on neuropathic pain due to sciatic nerve constriction injury in mice. All data are from the hindpaw ipsilateral to the sham or actual surgery. The ketogenic diet was 6.6:1. Number of subjects is 10-11. *p<0.05 versus sham surgery. Unpublished data.

Figure 6

Ketogenic diets have little effect in rats on the neuropathic pain due to the chemotherapy drug paclitaxel. Baseline measurements were taken just prior to injections. Number of subjects is 12 in all groups. *p<0.05 versus vehicle. Unpublished data.