The infectious disease threats facing soldiers are multiple and vary with geography. In fact, during major wars, infectious diseases usually have accounted for more noneffective days than combat wounds or nonbattle injuries. Combined stressors may reduce the normal ability of soldiers to resist pathogens, may increase susceptibility to biological agents employed against them, and may reduce effectiveness of vaccines intended to protect them. Studies in multistressor environments, such as basic training and the Special Forces' assessment and selection course, demonstrated that higher energy intakes better sustained indices of immune status (even in the face of other stressors). Regardless of operational stressors, troops must be supplied with high quality foods that will enable them to sustain performance and that will counter an array of immunological impairments caused by a host of unknown stressors.

The request for a review of the role of nutrition in immune function and its application to military operations originated with Army scientists from the U.S. Army Research Institute of Environmental Medicine (USARIEM) and U.S. Army Medical Research and Materiel Command (USAMRMC). In December 1995, a subgroup of the Committee on Military Nutrition Research (CMNR) participated in a series of conference calls with USARIEM, USAMRMC, and CMNR staff to identify the key areas that should be reviewed and to solicit suggestions for participants who were active in the research fields of interest. On May 20–21, 1996, the CMNR convened a workshop with presentations from individuals with expertise in nutrition and immune function. The two days following the workshop, the committee met to review workshop papers, additional literature obtained by staff, and begin drafting their summary and recommendations.

Additional writing sessions were held September 18–19, 1996, January 29–30, 1997, and March 13–14, 1997.

The Committee on Military Nutrition Research (CMNR) was tasked with assessing the current state of knowledge about immune function to ascertain how military stresses (including food deprivation) could impact unfavorably upon these functions and to evaluate ongoing research efforts by USARIEM scientists to study immune status in Special Forces troops. The committee was asked to include in their response the answers to the following five questions: The speakers invited to the workshop were also asked to address these questions in their presentations and in their chapters.

1. What are the significant military hazards or operational settings most likely to compromise immune function in soldiers?
2. What methods for assessment of immune function are most appropriate in military nutrition laboratory research and what methods are most appropriate for field research?
3. The proinflammatory cytokines have been proposed to decrease lean body mass, mediate thermoregulatory mechanisms, and increase resistance to infectious disease by reducing metabolic activity in a way that is similar to the reduction seen in malnutrition and other catabolic conditions. Interventions to sustain immune function can alter the actions, nutritional costs, and potential changes in the levels of proinflammatory cytokines. What are the benefits and risks to soldiers of such interventions?
4. What are the important safety and regulatory considerations in the testing and use of nutrients or dietary supplements to sustain immune function under field conditions?
5. Are there areas of investigation for the military nutrition research program that are likely to be fruitful in the sustainment of immune function in stressful conditions? Specifically, is there likely to be enough value added to justify adding to operational rations or including an additional component?

• Many stressful conditions encountered by military personnel have immunological consequences.
• The military's use of prophylactic immunization provides sufficient benefits beyond risk to warrant continued development.
• Pharmacological agents such as aspirin, ibuprofen, and glucocorticoids, which modulate the effects of cytokines, can be used to minimize signs and symptoms of cytokine-induced acute-phase reactions and the nutrient losses that accompany them.
• Evidence to suggest that the administration of recombinant cytokines can modulate immune function in a desirable manner is limited.

• Field studies must be based on the results of prior experiments conducted in controlled laboratory and clinical settings.
• Total energy intake appears to play the greatest role in nutritional modulation of immune function.
• The nutritional status of soldiers should be optimized prior to deployment,
• Nutrients that appear to play a role in immune function include protein, iron, zinc, copper, and selenium; the B-group vitamins, especially, B₆ , B₁₂ , and folate; vitamin A and its precursor, β-carotene, vitamins C and E; the amino acids glutamine and arginine; and the polyunsaturated fatty acids.
• The effects of providing supplements of vitamins A, C and E, as well as certain polyunsaturated fatty acids and amino acids, prior to, during, or following infections are virtually unknown in young, healthy adult men.
• Excess iron as well as iron deficiency may compromise immune status.
• Glutamine has demonstrated potential for improving immune function in critical illness, but its usefulness in healthy populations is unknown.
• Risks associated with excess consumption of supplements are much more likely for some nutrients than for others. Toxicity and the potential for nutrient-nutrient interactions must be considered individually.

• Use medically appropriate and directed prophylactic medications and procedures to minimize the adverse effects of infectious agents. However, there appears to be no potential value at this time in administration of cytokines or anti-cytokines to healthy military personnel.
• Vigorous research efforts should be undertaken to create and evaluate militarily relevant oral vaccines.
• Military personnel should maintain good physical fitness via a regular, moderate exercise program as a means of sustaining optimum immune function.
• Use methods to minimize psychological stresses, including training, conditioning, and structured briefing and debriefing.
• In view of the compromised immune function noted in studies of Ranger trainees, individuals who have lost significant lean body mass should not be redeployed until this lean mass is regained.
• Nutritional anemias should be treated prior to deployment and individuals classified as anemic¹ and requiring iron supplements should not be deployed.
• Develop and implement nutrition education programs targeted at high-risk military groups, such as Special Forces troops and female soldiers, to communicate information regarding healthy eating habits and supplement use.

• General supplementation of military rations above MRDA levels for the purpose of enhancing immune function is NOT recommended.
• The preferred method of providing supplemental nutrients is through a ration component.
• Gain a better understanding of the prevalence of supplement use and abuse by personnel and make strong recommendations for their appropriate use or nonuse.
• Conduct research to determine the appropriate field measures (see Table S-2) for monitoring nutritionally induced immune responses, particularly the presence of acute-phase reactions and changes in immune function of the type and degree that are likely to occur as a result of the nutritional insults suffered by soldiers in typical deployment situations.
• Carefully design research protocols.
• Increase awareness of and potential military application of findings within the civilian research community regarding nutrition and immune function.

• Perform laboratory-based studies as recommended previously (IOM, 1997) to determine if an interleukin-6 (IL-6)—creatinine ratio (or some comparable measure) can be measured in single ''spot'' urine samples as an index of the 24-h excretion of IL-6 and determine if 24-h IL-6 excretion is, in turn, a reliable indicator of acute stress response.
• Develop and field test appropriate cytokine markers in urine and blood that are reflective of ongoing acute-phase reactions and of changes in immune status in multistress environments.
• Research conducted on the ability of nutrients to influence immune status should place priority on the antioxidant nutrients β-carotene and vitamins C and E.
• Keep apprised of research being conducted in the civilian sector on immune function in physically active women and consider conducting studies on military women in situations of deployment to augment the findings of civilian studies.
• The influence of iron status on the risk of infection requires further investigation. This is also an area of interest to the civilian medical community.

<><><><><><><><><><><><>

The committee's responses to the questions, conclusions, and recommendations from this report are included in Appendix L.