Novel Nutritional Immune Formula Maintains Host Defense Mechanisms

Military combat and training stress induce immune changes that increase the risk of infection and ultimately influence soldiers' performance and readiness. Strenuous military training/assessment provides a uniform stress and the opportunity to evaluate nutritional strategies to minimize stress-induced immune changes that predispose soldiers to infection. Immunological changes and effects of a novel nutritional immune formula (NNIF) were examined prospectively in a double-blind, controlled study of 200 soldiers attending Special Forces Assessment and Selection School. Immune function was measured by skin delayed-type hypersensitivity, lymphocyte phenotyping, mitogenic proliferative responses, and granulocyte function. Approximately 50% of soldiers completed the study (control, n = 57; NNIF, n = 50). Several stress-induced lymphocyte changes were observed (decreased mitogen-induced proliferation, T and total lymphocytes, and interferon-γ-producing lymphocytes and increased percentage of neutrophils). NNIF modified several changes, including delayed-type hypersensitivity responses (NNIF, 78%; control, 59%; p

Introduction

The relationship among immunity, physical and/or psychological stress, and increased risk of infectious diseases has been the focus of investigations in recent years.1-5 Military stress (crowding, sleep deprivation, strenuous activity, malnutrition, psychological/physical pressure, and deployment) was shown to impair immune function and increase susceptibility to infection.6"11 This stress may contribute to higher rates of respiratory infections among military trainees, compared with civilian populations,12'14 thereby decreasing military readiness. Military training scenarios provide an opportunity to characterize stress-induced immune dysfunction and to evaluate strategies to improve trainee immune status.15

It has been shown that immune cell changes can predispose a person to respiratory tract infections16 and the decline in lymphocyte function can influence the susceptibility to infection.17 Previous studies noted immune cell changes resulting from military stress.7,9,18,19 Similarly, nutrient deficiencies can also cause immune cell changes.20-22

Nutrition has been linked to cellular pathways essential for effective immune function,20,23 and administration of selected supplemental nutrition may attenuate stress-induced immune changes. Several reviews have summarized the impact of individual nutrient deficiencies and their influence on immune function.20,24,25 For example, zinc deficiency reduced effective immune function, whereas supplemental zinc improved immune system responsiveness.26 Plasma zinc levels decline among soldiers participating in intensive military training,27 as a result of elevated urinary excretion, although the decline is not classified as an "overt" nutrient deficiency.28 Soldiers may benefit from selected supplemental nutrition to meet the demands of increased metabolism for optimal immune function, thereby improving soldiers' readiness.

During training, soldiers experience oxidative stress.29 Free radical accumulation can result in tissue injury, delayed wound healing, and increased susceptibility to infectious diseases.30 Immune cells modulate free radical oxidation using concentrated antioxidants.31 Antioxidants play a role in proper function of immune cells (i.e., neutrophils) and help prevent oxidative stress and immune function decline.32'35 In a previous study, the diets of soldiers were supplemented with a combination of antioxidants and food to attenuate oxidative stress. Soldiers participating in Special Forces Assessment and Selection School (SFAS) whose diets were supplemented with a mixture of anti- ' oxidants (n = 50/group) experienced modest attenuation of the stress-induced dysfunction (mitogen-induced lymphocyte proliferation).15

Dietary lipids may influence soldiers' physical readiness by providing an energy source to meet increased physical demands and may also influence immune function.36 Random reesterification of medium-chain fatty acids with long-chain fatty acids yields structured triacylglycerols or structured lipids that retain characteristics of both fatty acids. Feeding fish oil-derived structured triacylglycerol, containing medium-chain triacylglycerol, to patients undergoing surgery resulted in fewer infections in this susceptible population.37 Structured triacylglycerols have also been shown to increase the absorption of fat-soluble nutrients important for immune function.38,39

The gastrointestinal tract contains many immune cells and can be influenced by nutrition. For example, fermentable car-, bohydrates maintain gut/immune health and are substrates for bifidobacteria and other beneficial bacteria.40 Mounting evidence suggests that fermentable carbohydrates are also beneficial to the immune system and general gastrointestinal health.41,42

This study characterized immune cell changes that occur during physically and psychologically stressful military training (SFAS) and assessed the immunological effects of a novel nutritional immune formula (NNIF). Ingredients included nutrients known to affect immune function, i.e., vitamins, antioxidants, minerals, fructooligosaccharides, structured lipids, taurine, and carnitine. The comparison formula was an isoenergetic, isonitrogenous, control formula.

Methods

Subjects

Two hundred male U.S. Army soldiers (19-36 years of age; mean, 26.4 years) volunteered to participate in this study. Soldiers participating in the 21-day SFAS course were recruited from the April 1996 and October 1996 classes conducted by the U.S. Army John F. Kennedy Special Warfare Center and School (Fort Bragg, North Carolina). SFAS is designed to assess a soldier's physical, emotional, and mental stamina, to predict success potential in Special Forces training. Before entering SFAS, soldiers were screened for physical and medical fitness; only those deemed "healthy" (defined as the absence of any physical limitation, injury, illness, or chronic disease) were allowed to participate. Volunteers were informed of the study purpose and potential risks and benefits and signed an informed consent form before participation. The study was performed in accordance with the Helsinki Declaration of 1975 and the 1983 revision and was approved by the Human Use Review Committee, U.S. Army Research Institute of Environmental Medicine.

Soldiers participating in SFAS were not allowed to consume nutritional supplements during the course. Tobacco use by soldiers, although allowed, was not evaluated as a study variable. Soldiers were also allowed to consume nonprescription antiinflammatory and analgesic medications, dispensed by the medical clinic, as needed.

Design

This prospective, double-blind, controlled study randomized subjects to receive control formula or NNIF. Subjects enrolled during the first 2 days of the SFAS course, during a period of administrative activities (mild stress). On day 3 (baseline, study day O), between 4:00 a.m. and 6:00 a.m., subjects were weighed and blood samples were collected. Subjects consumed control formula or NNIF and recorded food and fluid intakes daily from baseline (study day O) through 19 days of strenuous military training (Fig. 1).

A second blood sample was collected on study day 17, between 4:00 a.m. and 6:00 a.m. Subjects were weighed, and a delayed-type hypersensitivity (DTH) test was administered by one physician. All DTH skin test indurations were measured by the same physician, -36 hours after administration (Fig. 1).

Formulas, Diets, and Body Weights

Control formula and NNIF (similar in appearance and taste) were manufactured by Ross Products Division, Abbott Laboratories (Columbus, Ohio), in accordance with good manufacturing practices. Soldiers consumed 237 mL ( 1,500 kJ, 360 kcal) of formula twice daily. The formulas contained similar amounts of energy, fat, and carbohydrate but with differing amounts of nutrients reported to affect immune function or to be important for energy metabolism (Table 1). The study formulas were typically dispensed by study personnel; subjects immediately consumed their formula and returned the emptied can. Subjects also consumed normal military rations, consisting primarily of "meals, ready to eat." Body weight was measured at baseline and study end, using a calibrated, digital, electronic, battery-powered scale (accurate to 0.1 kg).

Blood Sample Collection