Thursday, July 7, 2011

Ketones and environmental toxicity

It is a well known fact that ketone bodies protect cells from oxidative stress and apoptosis (1,2,3,4,5). Because toxicity from different environmental toxic substances can be modulated by nutritional status, and specifically, dietary macronutrients, a ketogenic diet could reduce greatly the risk of several associated diseases. 

Soman is an extremely toxic substance which inhibits cholinesterase activity, having profound effects on the CNS. Increased exposure can ultimately lead to death. Langston and Myers (6) tested the influence of diet on soman toxicity in rats. For this purpose, rats were fed four different diets: standard (SD), choline-enriched (CH), glucose-enriched (GL) and a ketogenic diet (KD). The doses used in this study were 0.4-0.5 of the acute 24-h LD50. This dosing regimen was chosen to induce significant cumulative toxicity that would permit characterizing differences in the rate of onset of soman toxicity, the degree of toxicity, and the rate/degree of recovery from soman toxicity as a function of diet composition. Macronutrient composition (as percentage of total calories) was as follows (protein/carbohydrates/fat):

SD: 32.4/54.2/13.4
CH: 32.5/54.2/13.3
GL: 20.2/66.8/12.9
KD: 14.3/0.4/85.3

After 4 weeks, KD-fed rats and CH-fed rats weighted less than SD and GL. But this is not in what I am interested. Lets see how the different diets affected soman mediated toxicity.

From the graph, we can see a clear trend on survival among the different diet groups. 30% of the GL group died after the third administration of soman (0.4 LD50) and the remaining 70% died after the fourth administration of 0.5 LD50. At this cumulative dose (352ug/kg), only 10% of the SD group died, while all of the rats fed a KD and CH survived. When the cumulative dose was greater than 400ug/kg, we can see how the lines representing the CH and SD groups begin to fall. At this point, both groups had an approximate terminal survival value of 55%. In contrast, only one animal in the KD group died after the final soman administration (cumulative dose of 627ug/kg). 90% of KD-fed rats survived. 

Soman administration also reduced the body weight of exposed animals. For simplicity, I will only compare the GL and KD groups. CH and SD rats only lost weight in the last week of exposure, as well as through the recovery period (SD). Time vs. weight graphs are shown below (x represent soman/saline injection days; o represent non-injection days):

GL rats started to lose weight rapidly after soman exposure, compared to vehicle animals. This was evident as early as the second week. Now, lets compare the body weight on soman-exposed animals fed a KD.

KD rats showed little (non significant) weight loss after soman exposure. The only little difference observed was at the maximum cumulative dose.

The last parameter measured by the researchers was avoidance behaviour. Again, I will compare only the GL group with the KD group.

Rats fed an enriched glucose diet had disrupted avoidance performance during the initial 3 days of exposure to 0.4 LD50 of soman. During recovery, avoidance responses were recovered and then were completely supressed (at 0.5 LD50). In contrast, avoidance responses in the KD were only compromised during the final week of exposure. Although the CH group also maintained avoidance responses until the last week, performance in the KD was greater. 

Results were similar for the time spent in the aversive stimulus (AS) (in this case, a scrambled 1.0-mA shock with a frequency of 1.0Hz, 0.5s shock on/0.5 shock off). During the second week of exposure, GL rats failed to respond to the AS and they all died by the end of the week. Once again, KD rats performed the best. AS time was maintained during the entire exposure period. 

Summing up, the authors stated:

"Specifically, all KD animals survived a cumulative 5.0 LD50 dose of soman, whereas all glucose animals died following a cumulative 3.2 LD50 dose of soman. Not only was survival enhanced in KD animals, but there were also minimal differences in body weights compared to dietary controls injected with saline. Furthermore, KD animals exposed to soman exhibited few performance decrements on an avoidance task, and there were fewer instances of behavioral incapacitation in KD animals compared to the other diet groups."

Glucose feeding has shown to exacerbate toxicity from other substances, such as organophosphorus pesticide parathion (PS) (7,8). Interestingly, Slotkin et al. (9) showed that a high-fat ketogenic diet reversed the neurodevelopmental effects of neonatal PS exposure. 

Although the studies mentioned were done in rats, it seems plausible that the effects could be reproduced in humans. Judging by the results, a ketogenic diet could help treating as well as preventing environmentally mediated toxicity. 

ResearchBlogging.orgLangston JL, & Myers TM (2011). Diet composition modifies the toxicity of repeated soman exposure in rats. Neurotoxicology PMID: 21641933


  1. I wonder what would've happened had the glucose replaced fat instead of protein.

  2. What did the ketogenic diet consist of?

  3. Hi john,

    This was the KD used:

    The fatty acid profile, according to another study which used the same formula is given in the following table:

  4. Hey Lucas,

    Awesome study compilation. I posted the article on my facebook page - it's geared towards low-carb lifestyles and various health impacts (not limited to weight-loss). Check it out, and if you write more articles like this, feel free to give me a shout and I'll post em.