A reader from the U.S. Army writes:

“I would like to know how I volunteer for experimentation as a test subject in the field of gene therapy? Who do I contact? Where do I get more information? Sir, I would really appreciate your help. I have for a long time now thought that gene reprogramming and therapy have awesome potential for all of us who seek to obtain our greatest strength and our best bodies.”

Research teams from the Walter Reed Army Institute of Research (Washington, DC 20307-5100) have reported use of liposomes and the Shigella virus to deliver DNA for gene therapy. Also a major program to invent vaccines and “bioscavengers” that will counter Biological Warfare agents is underway at the Army Medical Research Institute of Infectious Diseases (Fort Detrick, Frederick, MD). Therefore, both institutions have the expertise and facilities required for gene therapy experiments. Short description of these and other Army research facilities can be found at the Battelle web site.

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Introduction

I would like to review some of the developments in performance enhancement as they relate to the armed forces, since this subject is not well understood by civilians. Mesomorphosis readers will know that use of ergogenic agents usually gets a “bad rap” in the news media. It seems we are always hearing about athletes who have tried to win by taking prohibited doping substances. In other words, cheaters.

However, all is fair in war, and some of the same substances that could cause problems if used recreationally can also save your life in combat. As one author observed in an article on ephedrine, “Aside from health risks, the ethical concerns of using ergogenic aids banned by sport regulatory bodies are of no relevance to military operations” [Bell1998].

Military Policy

U.S. Defense Technology Objectives are spelled out in planning documents available at the Defense Technical Information Center. The DTO document for 1998 includes these objectives (FY = fiscal year):

FY1998: Develop recommendations for an operational doctrine for pharmacological intervention to counter fatigue and sleep loss in military operations, improving the performance of personnel experiencing 72 hours without sleep by 35%.

FY1999: Provide joint guidance for commanders, integrating knowledge of sleep loss, melatonin, shift work schedules, and performance decrements for conducting rapid deployments and sustained operations to reduce performance decrements by 25%.

Use of ergogenic agents is official policy in the military. Of course this is not the only means of improving performance. In fact it is fairly minor compared to other factors. Nevertheless it is official, and millions of dollars are budgeted each year to improve knowledge about and supply of ergogens.

Nor is this solely a U.S. phenomenon. Canada’s Defence and Civil Institute of Environmental Medicine (DCIEM) reports that:

Studies of the effects of nutritional and/or pharmacological treatments demonstrated significant performance enhancement effects caused by creatine, and the combination of caffeine and ephedrine. … Ergogenic aid research will evaluate the effects of modafinil and dichloroacetate treatments on exercise performance.

In fact, there is no military force that does not use medications and nutrients to improve performance. To eschew such aids would be to give the performance edge to the enemy. A 1986 conference on Biochemical Enhancement of Performance brought together scientists and physicians from all the NATO countries to compare notes on substances as novel as Delta-Sleep-Inducing-Peptide and as old as methamphetamine sulfate.

The Navy

The Naval Health Research Center Special Operations Division is described as follows:

The NHRC Special Operations Division, composed of exercise physiologists, exercise biochemists, nutritionists, and statisticians, works with the special forces community on a daily basis to study the efficacy of physical training, nutritional and ergogenic interventions. Nutritional strategies include carbohydrate loading and supplementation, creatine supplementation, and hyperhydration. Guidelines for applying these interventions have been published and distributed to special operations commanders and medical officers.

In 1997 a team of NHRC researchers under the direction of Dr. H.W. Goforth conducted a survey of Navy SEALs to determine their supplement use. They found that 78% of the SEALs has consumed at least one supplement in the previous year, and 66% had used three or more supplements. Only 57% who had taken supplements to enhance muscle mass and power thought they had been effective. Adverse effects reported were nausea and other gastrointestinal effects.

Notably, the SEALs reported that their sources of information were friends (79%), team members (63%) and magazines (49%). Only 24% had received information on supplements from a health care provider. The authors observed: “This finding suggests that the Navy medical community should take a proactive role in providing accurate scientific information on the risks and benefits that can occur with nutritional supplement use.”

The Army

The Army has a special interest in reducing the effects of chronic physical stress. Much of the research on performance enhancement is conducted at the U.S. Army Research Institute of Environmental Medicine in Natick, MA 01760-5007. They have a Performance Enhancing Ration Components Program (PERC) underway, with the objective “to demonstrate that specific natural food constituents, like carbohydrates and caffeine, can enhance physical and mental performance of soldiers in the field.” Goals of the PERC program are:

• Provide extra energy and delay fatigue.
• Improve response time and decision-making.
• Minimize performance decrements under stress.
• Enhance situational awareness.
• Maximize unit success.

Here is a brief description of the program:

This program is not intended to develop a new ration but rather to provide supplemental ration components for currently fielded rations. These new developmental ration components are intended to improve performance of soldiers exposed to the many stressors associated with military operations such as rapid deployment, environmental extremes, sustained and continuous operations and extreme physical demands. This program involves scientists from many different disciplines, including food technologists, biochemists, dietitians, physiologists and psychologists.

To date several laboratory and field studies have been conducted with promising results. In one laboratory study, a carbohydrate beverage was tested with volunteers from a Special Forces unit that ran for several hours on a treadmill. When a soldier received the carbohydrate beverage while running he could continue for 16% longer than when a placebo beverage was administered.

Another possible PERC ingredient is an amino acid found in most protein foods, tyrosine, which may prevent some of the adverse effects of exposure to environmental stresses such as cold and high altitude. Other amino acids and also antioxidants may enhance immune function.

You can read the entire article from Warrior magazine.

The Air Force

The skill and performance of individuals — especially pilots — are critical to the success of Air Force missions, and therefore this service has taken the lead in assessment and prediction of cognitive and psychomotor abilities [King1995].

In 1997, the Air Force Research Laboratory was established to administer the various research environments. However, human performance research continues to be the main concern of the Armstrong Aerospace Medical Research Laboratory, located at the Wright-Patterson air base in Ohio and at the Brooks air base in Texas. A special concern of researchers at this laboratory is the circadian timing system (the biology underlying fatigue), especially the brain processes involved in regulating adaptation to changes in state from sleep to waking to arousal. For example, a study of air traffic controllers [Luna1997] found:

Safety concerns have been raised because the air traffic controllers (ATCs) often carry an acute sleep debt onto the night-shift where they have little active work to do as they sit in the dark at the nadir of their circadian rhythms. … Recent studies indicate that ATC performance declines on the night-shift and that ATCs may be falling asleep while on-duty.

To counter this sort of problem, an alertness monitoring system is being developed. As we’ll see in future parts of this series, pharmacological solutions are also being investigated.

A second area of research is aimed at finding electrophysiological measures of “cognitive overload.” In other words, determining when more information is arriving than can be processed, and devising ways of dealing with such problems. Solutions may be be found in improved interfaces, but also in finding ways to improve cognition.

Nutrition and Dietary Supplements

So much for the generalities. We know now that study and use of ergogenic substances is official policy in the military, that it is pursued in all branches of the armed forces, and for that matter in all major armed forces world-wide. Now lets begin a survey of some of the specific substances considered for use.

The Losers

Military research is as valuable for showing us what doesn’t work as for showing what does. Here are three examples of substances for which claims of efficacy have been made, but they showed no benefits when put to the test.

• Ginseng.  A research team from Canada’s DCIEM provided volunteers with ginseng capsules designed to provide doses of either 8 or 16 mg/kg of their body weight per day. In other words, a man weighing 220 pounds would be taking either 0.8 or 1.6 grams per day — a substantial dose. The volunteers consumed ginseng daily for a week and then exercised on a stationary bicycle (ergometer). Measurements were made of blood glucose, lactate, etc. The data showed “There is no ergogenic effect of ingesting the ginseng saponin extract” [Morris1996].
   
• Choline.  Choline is a precursor of acetylcholine, a neurotransmitter. It has been suggested [Conlay1992] that under conditions of strenuous exercise the level of acetylcholine could be depleted, and that supplementation of choline could enhance performance under these conditions.Researchers at USARIEM and North Carolina University worked with 14 Army Rangers on this experiment. The rangers drank a liquid containing either placebo or 8 grams of choline and after a 1/2 hour rest they walked for 20 kilometers on treadmills (about 4 hours), wearing 65 pound rucksacks. Halfway through the walk, another ration of choline or placebo was consumed. Immediately after the hike, tests were conducted to determine time-to-exhaustion, squat strength, perceived exertion, marksmanship, short-term memory, mood states, lactate, glucose, CPK, lipid and plasma choline. The choline levels were not depleted in the placebo group, and no advantage was observed in taking choline [Warber1997].
   
• Chromium Picolinate. Trent and Thieding-Cancel studied nearly 100 men and women who had been referred for exceeding the Navy’s percent body fat standards of 22% fat for men or 30% for women. Each person took a capsule per day containing a placebo or else 400 micrograms of chromium picolinate. At the end of 16 weeks the chromium group did not show superior fat loss compared to the placebo group, nor did they have a greater increase in lean body mass. Conclusion: “Chromium picolinate was ineffective in enhancing body fat reduction in this group and could not be recommended as an adjuvant to Navy weight-loss programs in general.” A more recent report shows chromium is useless for building muscle: “Chromium picolinate supplementation has no effect in the augmentation of changes in body composition or muscle size or function when used during a resistance training program by older men” [Campbell1999]. In fact, in this latter experiment, the subjects taking placebo made superior strength gains!

^{Worth Investigating}

Following are some of the areas in nutrition and supplementation that either show promise or for which definite benefits have been established.

• Zinc. Miyamura et al. reported studying thirty Army men engaged in a month-long training exercise that simulated war operations. During this time they consumed fresh, nutritionally adequate food (A rations). Dietary intake was monitored. During the month the soldiers lost weight, serum zinc levels declined, and urinary zinc excretion increased. Weight loss was positively correlated with the zinc loss. The authors note that “The depressed serum zinc concentration could not be explained by the parameters measured.” Therefore it looks like supplementation with the right amount of zinc may improve the health and performance of soldiers under these intense conditions.
• Creatine. (Caution!) Creatine is a proven ergogen. Those not familiar with its effects can read the review on this site by Richard Kreider of the University of Memphis, or a more rigorous essay by the same author from the Journal of Exercise Physiology. Unfortunately, Dr. Kreider minimizes the risks involved in creatine use. As he has received large grants from Experimental and Applied Sciences (EAS), a distributor of creatine, and since Krieder’s findings are used in EAS advertising, he can not be considered objective. A much better review of possible adverse effects of creatine use is the recent paper by Mark Tarnopolsky of McMaster University [Juhn1998].If your physical exercise is limited to workouts at the gym, then creatine can help you. However, it has no value for endurance type exercise like running or hiking long distances [Balsom1993]. Moreover, adverse effects such as gastrointestinal upset and cramping are more likely to show up during endurance exercise. Since military maneuvers often require endurance, the utility of this ergogen for the armed forces is limited. It will probably be useful for soldiers who are vegetarians and for those whose duties involve a greater strength than endurance component.

What is Oxygen Deficit?The concept of oxygen deficit was introduced by Scandinavian physiologists Krogh and Lindhard [Krogh1920]. It is the oxygen cost of work performed, compared to the actual oxygen consumed, less the resting VO2 (oxygen consumption). Jan Karlsson later observed that oxygen deficit was about the same regardless of whether exercise time was 2 or 15 minutes. Based upon this observation, Norwegian physiologist Jon Medbø has suggested that accumulated oxygen deficit could be used as a measure of anaerobic capacity, defined as the greatest anaerobic energy production an individual can obtain at any exercise performed to exhaustion [Medbo1988, Medbo1996]. Some of the assumptions used in determining anaerobic capacity have been criticized by Jen Bangsbo of Denmark (summarized in the October 1996 issue of Canadian Journal of Applied Physiology), but consensus seems to be that it is a valuable metric in studies involving repeated bouts of the same type of exercise. In particular, once the maximum anaerobic capacity of a person is known, then scientists can assess the impact of performance enhancing substances, by having the person consume the substance and repeat the exercise test.

Dr. Ira Jacobs and coworkers at the DCIEM examined a group of two dozen volunteers, half of whom consumed 20 g/day creatine for 5 days, and half of whom received a placebo. Maximum accumulated oxygen deficit (MAOD) tests were given before, after, and 7 days after treatment. Twelve of the 14 subject who took creatine had an increased MAOD, while there was no significant increase in controls. The MAOD remained at a higher level 7 days after the 5 day supplementation period. Time to exhaustion was also significantly increased in the creatine group [Jacobs1997].

This means that in most subjects, creatine increased the maximum capacity for anaerobic work. It also shows that there are some people who are non-responders to creatine supplementation.

An additional benefit of creatine has been discovered by a research team from USARIEM, Boston University, and Harvard [Montain1998, Smith1998]. The amount of phosphocreatine (an energy substrate) that is present in the muscles of middle aged people is significantly less than that younger adults, accounting for some of the differences in strength between the two groups. When a group of men and women with average age 30, and another group with average age 58 were given creatine for 5 days, phosphocreatine levels rose in the young group by 15%, but they rose by 30% in the older group. The final average levels in both groups were exactly the same. So this means that creatine supplementation can eliminate one source of age-related weakness.

• Glycerol. It is known that consuming glycerol with water increases the amount of water retained in the body — a state called hyperhydration [Freund1995]. This has led to speculation that glycerol may be effective in reducing water loss during undersea dives in cold water [Arnall1993]. However, it was found to have no effect. Another hypothesis was that glycerol might improve sweating responses to hot temperatures and thus help cool people down. In this case also it was found to be ineffective [Latzka1997]. What we’re left with is that glycerol can help increase and retain water in the body. This can be an aid during runs, forced marches, and any situation where dehydration might occur.
• Tyrosine. The jury is in on tyrosine, and it’s a winner. Report after report has shown tyrosine to be effective at reducing performance problems due to stress — whether that stress is caused by environmental factors such as cold or high altitude, or by lack of sleep, or by pain and emotional stressors.The reason tyrosine works is because it is a precursor for the catecholamine neurotransmitters dopamine (and DOPA, which is an acronym for 3,4-DihydrOxyPhenylAlanine), epinephrine and norepinephrine. When you take a large amount of tyrosine, it saturates an enzyme called tyrosine hydrolase. The result is acceleration of catecholamine synthesis.Under normal conditions, having more of these neurotransmitters won’t do you a lot of good, but when you’re stressed your neurons have to work overtime to pump out the catecholamines, especially norepinephrine. After a while, the supply can’t keep up with the demand, and you experience a behavioral and cognitive deficit. In other words, you become depressed, lethargic, you forget things, and you have trouble maintaining attention. This state is fairly common in war, and in fact it is one reason for the “softening up” round-the-clock bombardment such as took place in Desert Storm.Tyrosine comes to the rescue in this situation by boosting catecholamine synthesis back to near-normal levels. Moreover, it has secondary effects like reducing cortisol production (cortisol is a catabolic hormone) and improving mood. Figure 1 shows the effect of tyrosine on corticosterone in rats. This is directly analogous to a reduction of cortisol in humans.
  Figure 1: Tyrosine reduces corticosterone resulting from acute stress (source: Reinstein1985).In a pioneering experiment, Louis Banderet from USARIEM and Harris Lieberman from the Massachusetts Institute of Technology exposed 23 Army volunteers to conditions of cold and hypoxia (low oxygen levels) typical of conditions in mountainous terrain. Each subject received either a placebo or else 100 mg/kg of tyrosine. The exposure was for 4 1/2 hours, during which time the subjects were tested for mood, drowsiness, performance of various tasks involving mental acuity, etc. Later, there was a “crossover” in which subjects previously taking placebo took tyrosine, and vice-versa. The results were consistent: tyrosine reduced symptom intensities and performance impairments, with absolutely no side effects (see Figure 2).
  Tyrosone improves symptoms of environmental stress (source: Banderet1989).As a further test of tyrosine’s efficacy, 36 members of Seal Team 2 volunteered to try tyrosine in Winter Warfare training, from January to March in Alaska. Either 6 grams of tyrosine or a placebo were consumed by the men, who were then exposed to temperatures as low as -22° C (-10° F). The authors of the report [Schrot1994] write: “On average the subjects who consumed placebo showed performance decrements on acquisition and memory tasks following cold exposure, while the subjects who consumed tyrosine had test scores comparable to those obtained under baseline conditions.“Dosing. Doses of up to 150 mg/kg have been used in the experiments on humans, with no adverse effects. In other words, if you weigh 100 kilograms (220 pounds), you could take 15 grams at a time. Tyrosine competes with other amino acids to cross the blood-brain barrier, so it should be taken in the absence of protein for maximum effect [Wurtman1987]. Eating it with carbohydrates increases the effect. In some of the experiments, tyrosine powder was mixed with apple sauce. Note that in the Seal Team experiment, doses of 6 grams were used.The ideal way to take tyrosine would be in a special candy bar. In fact, the U.S. Army is reportedly designing such a ration which also contains caffeine.
  Figure 3: Tyrosine raises catecholamine levels
  (source: Agharanya1981).

Conclusion

“Future military operations will present unprecedented challenges. Combat is likely to be intensive, quick-paced, and fought day and night. Dramatic sleep loss, altered work-rest cycles, uncertainty, and misinformation will also be commonplace. Troops are also likely to be rapidly deployed to environments very different from that to which they are acclimated.”
Biochemical Enhancement of Performance, (NATO publication).

While the nature of warfare is changing to depend more on the skills of the individual soldier, the pressures on individuals are also increasing. Methods of enhancing performance and overcoming performance impairments are part of the equation now, as much as training and screening of staff. In Part 1 of this series, we’ve seen that performance enhancement is officially sanctioned and mandated, and we’ve reviewed some of the research on nutritional aspects. Next month we’ll look at techniques like “carb loading” that involve physiological manipulation. Then, in Part 3, we’ll review some of the pharmacological approaches being investigated, not only by U.S. forces, but also by the Brits, Canadians, French and the Russians.

References

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