Approximately 37% of today’s health-minded consumers are concerned about immunity, according to the 2007 HealthFocus Trend Report. The Internet is filled with immune-boosting promises in support of both health and profit. It is well established that undernutrition contributes to increased incidence of infection, decreased nutrient absorption, and elevated morbidity and mortality (Scrimshaw, 2003). On the other side of health, there are numerous acute and chronic diseases that, in part, may be the result of overnutrition or imbalanced nutrition that stimulates or prompts excessive expression of various components of the immune system, which contributes to inflammatory responses.

Healthy inflammation is localized and desirable. It is a typical, short-term—yet critical—response following injury and trauma that ultimately leads to tissue repair. Unhealthy inflammation is systemic and, if undetected for prolonged periods, may progress to affect organ systems. Systemic inflammation may trigger an array of metabolic disorders. This protracted response is characterized by a low-grade inflammation of adipose and other critical tissues, also known as a low-grade inflammatory response syndrome (Hotamisligil, 2006; Bastard et al., 2006; Cave et al., 2008).

Emerging clinical evidence suggests that fat cells (adipocytes), once thought to be metabolically inert, may represent dynamic sources of pro-inflammatory, metabolically active substances such as cytokines and reflect a potent dysregulation of the delicate metabolic homeostasis (De Lorenzo et al., 2007). Abnormal production of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), interleukin-1 beta (IL-1β), leukotriene B4 (LTB4), leptin, and numerous other inflammatory mediators, also called adipokines when secreted by adipocytes in white adipose tissue, lead to insulin resistance, increased blood pressure, and subsequent development of secondary illnesses.

Many of these secondary illnesses associated with obesity may reflect increased macrophage infiltration in adipose tissue. Macrophage infiltration is a classic inflammatory response. Yet the apparent excessive recruitment of macrophages by select chemoattractant proteins overexpressed in adipose tissue and the insufficient production of anti-inflammatory adipokines, such as adiponectin, proxisome proliferator-activated receptor-γ (PPAR-γ), and visceral adipose tissue-derived serine protease inhibitor, may be critical mechanisms that trigger pathophysiological processes involved in the preceding metabolic disorders.

The pharmaceutical industry targets many of these processes as approaches to inhibit the inflammatory processes. Could nutritional modulation elicit similar effects? Could the concept of “pharmanutrition,” also known as “immunonutrition,” decrease systemic inflammatory processes by down-regulating exaggerated pro-inflammatory responses, improve metabolism, and reduce the risk of chronic disease? With a few important caveats, the answers to these questions may involve nutritional intervention.

Animal models and human clinical studies indicate omega-3 polyunsaturated fatty acids and some monounsaturated fatty acids, through a cascade of events, can down-regulate production of pro-inflammatory cytokines, inhibit macrophage infiltration into adipose tissue, and favorably alter adiponectin levels via PPAR-γ activation (Cave et al., 2008). Animal studies indicate caloric restriction also down-regulates expression of pro-inflammatory genes while up-regulating anti-inflammatory genes (Fernandes, 2008). These kinds of studies also suggest dietary soy protein, magnesium, and zinc may have similar anti-inflammatory effects. In addition, these and other nutrients may function to selectively protect immune cells, maintain physical barriers, and support antibody production (Maggini et al., 2007).

Metabolic syndrome, diabetes, and cardiovascular diseases are co-morbidities of obesity. These serious healthcare conditions may be mediated through organ-dysfunctional and chronic inflammation (Cave et al., 2008) and may well represent opportunities for aggressive nutrition and food science interventions that target the immune system and associated inflammatory signaling pathways. The food industry has the opportunity to leverage the pharmanutrition concept and develop products that could decrease the inflammatory process while reducing obesity-associated morbidities.

References for the studies mentioned above are available from the authors.

by Roger Clemens, Dr.P.H.,
Contributing Editor 
Special Projects Advisor, ETHorn, La Mirada, Calif. 
[email protected]

by Peter Pressman, M.D.,
Contributing Editor 
Attending Staff, Internal Medicine, Cedars-Sinai Medical Center, Los Angeles, Calif. 
[email protected]