Dr Todd Myers and Dr Jeffrey Langston, Toxicologists from the Analytical Toxicology Division at USAMRICD tell Steve Johnson about the potential of their recent work on diet, and its effect on nerve agent toxicity


Eating for victory! Introduction


The last ten years have seen huge sums of money and some incredible breakthroughs in the development of medical countermeasures for CBRN agents. In the race to find the correct pill or injection to protect the warfighter, almost no time has been spent considering his diet and how it might potentially exacerbate or attenuate the effect of toxicity. Imagine how interested you would be if someone offered to double your chance of dying from a nerve agent exposure, or conversely double your chance for surviving, simply through diet change! While this is not to suggest that a diet change would be the appropriate response to an acute exposure, it is to question whether we have been thinking smartly about how a patient’s metabolism pre and post exposure can either work for or against their recovery. Recent ground-breaking research from US Army Medical Research Institute of Chemical Defense (USAMRICD) demonstrates that, in laboratory rats, diet can potently modify toxicity, resulting from acute or repeated soman exposure. It is likely that such effects extend to the human condition as well. Indeed, in their book A Higher form of killing, Harris and Paxman (1982) reported that exposure of German factory workers to low levels of tabun (GA) was so common that most workers at some time or another were intoxicated by tabun and would exhibit constricted pupils as one obvious sign. Eventually, all workers at Dyhernfurth were given extra milk and fat rations because it was observed that this diet offered increased resistance to these effects. Despite this fact being known, research into this has been virtually non-existent. Yet we do have evidence that poor diet can have a deleterious effect, and even that putting the body into a ketogenic state through fasting or a high-fat diet can control seizures.


Langston-Myers testing


In order to generate some empirical data about the effect of diet, Myers and Langston constructed an experiment to evaluate the role of diet composition on nerve agent toxicity. Four diets were selected and administered to rats for 28 days prior to the nerve agent exposure. They were then administered a single LD50 dose of soman, appropriate to their body weight.


The four diets used were a standard rodent diet, a choline-enriched diet, a glucose-enriched diet, and a ketogenic (high-fat, low-carbohydrate) diet. Body weight was recorded throughout the study. Toxic signs and survival were evaluated at key times for up to 72 hours following soman exposure. Upon exposure, differences in soman toxicity as a function of diet became apparent within the first hour, with mortality in the glucose-enriched diet group reaching 80% and exceeding all other groups (in which mortality ranged from 0 to 7%). By 48 hours after exposure, mortality was 100% in the glucose- enriched diet group. Incredibly, this is twice the expected mortality - a huge impact. The standard and choline diets behaved as expected, with mortality averaging about 50%. But even more incredibly the survival in the ketogenic group was 87% - a sizable improvement in survival.


In a second study, they


systematically replicated these results by examining the effects of these same four diets on repeated exposure to soman. Soman doses of 0.4 to 0.5 LD50 were administered three to five consecutive days per week for three weeks, resulting in a cumulative dose of up to 627 ug/kg, or 5.7 LD50. This repeated-dosing regimen was selected to induce significant toxicity and characterise differences in the rate of onset of soman toxicity, the degree of toxicity, and the rate and degree of recovery. At the end of dosing, survival approximated 55% in the standard and


choline diet groups, but was much higher in the ketogenic diet group wherein it equalled 90%. Once again, rats fed the glucose-enriched diet succumbed at much lower doses and all were dead after a cumulative dose of only 352 ug/kg, about half that administered to the other three diet groups. To provide an additional point of comparison, the dose producing 10% mortality in the ketogenic diet group was seven-fold greater than that in the glucose-enriched diet group. Similarly, the LD10 in the standard diet group was four-fold greater than that in the glucose-enriched diet group. These findings are of considerable significance because, in a mass-casualty scenario, even small shifts in toxicity could save lives. Across both studies, several other measures were recorded and the results corroborated the different diets’ effects upon survival. For example, clinical signs of nerve agent toxicity typically include salivation, tremor, and convulsions and these symptoms were greatly reduced in the ketogenic diet group, relative to all other groups following acute soman exposure. Body weight loss was also largely prevented in the ketogenic diet group relative to all other diet groups under acute and repeated soman exposure. Perhaps most importantly, Myers and Langston used a sensitive behavioural test in which rats could escape or avoid an aversive stimulus (mild electric shock) by moving from one compartment to another (shuttle box avoidance). Following acute nerve agent exposure, rats fed the ketogenic diet performed the task better than rats fed the standard diet. In the repeated-dosing experiment, the performance of rats fed the glucose-enriched diet showed severe impairments at much lower cumulative doses than any other. Likewise, the choline and standard diet groups exhibited performance impairments well before any such


CBRNe South America 2012, 13-14 March, Rio De Janeiro, Brazil. More information on www.icbrnevents.com 32 CBRNe WORLD February 2012 www.cbrneworld.com


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