Immunity ingredients have generated significant buzz in the nutraceutical arena, not least because they address the geometrically increasing concerns of an aging-yet-active population.

Inflammation mitigation is a key benefit in many immunity ingredients, irrespective of its “chicken or egg” status in regards to disease. For instance, a raft of recent research points to strong connections between inflammation and obesity, but whether inflammation is one of the factors that alter metabolism and increase propensity for weight gain or whether one of the body’s reactions to obesity is to engage the inflammatory response is not yet clear. And, both are likely the case vis-à-vis a cascade effect. Nevertheless, alleviating inflammation will in turn aid the body’s immune response.

A number of immunity ingredients have received attention for having beneficial attributes across several platforms, targeting inflammation, digestive health, tumerogenesis and obesity, which itself leads to a myriad of pre-disease and disease states. Effective weight reduction and management can help prevent or mitigate symptoms of diabetes, cardiovascular disease, kidney disease and even reduce risk of cancer.

For a machine as complex as the human body, externally augmented immune function can originate from a number of sources. These sources are not only divisible into classes, such as oils (e.g., omegas), carbohydrates (e.g., prebiotic oligo- and polysaccharides, beta-glucans) and proteins (e.g., soy isoflavones, colostrum peptides), but a scattering of other compound types that include probiotic bacteria, minerals, vitamins, co-vitamins, co-enzymes and botanicals/phytochemicals.

Immunity Vitamins

Among the vitamins, while antioxidant vitamins A and E have demonstrated strong effect at helping the body ward off diseases and counter cellular stress at the DNA level due to oxidative damage, vitamin D is being investigated as an immune booster after a flood of studies indicate this hormone-like compound does a lot more than just build strong bones.

Writing in The FASEB Journal, Drs. Hector DeLuca and Margherita Cantorna pointed out that, “[The] vitamin D receptor is found in significant concentrations in the T-lymphocyte and macrophage populations. However, its highest concentration is in the immature immune cells of the thymus and the mature CD-8 T lymphocytes. The significant role of vitamin D compounds as selective immuno­suppressants is illustrated by their ability to either prevent or markedly suppress animal models of autoimmune disease.”

In addition to noting a link between vitamin D (and calcium) status and diseases, such as rheumatoid arthritis and lupus, Cantorna investigated “the possible treatment or prevention of inflammatory bowel disease by vitamin D.” DeLuca and a number of other researchers have been studying strong indications of vitamin D as a possible influence on helping to prevent diabetes.

Since minerals are involved in all of the thousands of metabolic reactions that keep the body functioning, it’s a given they are critical to immune support. But, two minerals with direct impact to consider are zinc and selenium. Zinc, especially in its gluconate form, while not a proven cure for the common cold, is one of the few interventions scientifically backed for significantly reducing the severity and duration of the persistent bug. Selenium is unique, in that it is the only dietary mineral that functions as an antioxidant. It is involved in cell-mediated immunity and is believed to help boost immune response.

Moreover, selenium deficiency has been connected to an increase in pro-inflammatory cytokines and simultaneous decrease in anti-inflammatory cytokines. In a study of supplementation with selenium-enriched yeast, the compound was able to modulate inflammatory interleukin-8. In another study of elderly patients, who are more susceptible to flu viruses, selenium-rich yeast supplementation boosted response of the immune cells known as lymphocytes. Six months of said supplementation actually brought the seniors in the study to the same lymphocyte response levels as healthy adults.

Multifunctional Immunity

In the category of lipid-sourced immunity boosters, omega-3 fatty acids rapidly built up a foundation of research that puts them in the near-panacea category, helping to protect against a number of disease states and conditions—from cardiovascular disease and cognitive function to depression and arthritis. For protein-derived immune ingredients, a wealth of research in recent years has pointed to a number of compounds in dairy products (besides vitamin D) that could support overall immune function.

Milk proteins, and shorter fractions thereof (milk peptides), have demonstrated antibacterial and antiviral abilities, as well as improved cognitive function and protection at the cellular level. Dairy proteins also have shown cholesterol-modulating effects that could reduce cardiovascular disease risk.

Another significant, and well-known, protein-based source of immune protection comes from soy. In fact, the connection between soy—specifically soy isoflavones—and health could be the most studied one of all. Thousands of bodies of research support a role for soy isoflavones in helping to protect the body against cardiovascular disease, kidney disease, certain cancers, hyperlipidemia and menopause. Genestein, one of the key isoflavones in soy, is known as an estrogen (specifically, estradiol) mimic; it enhances cytotoxic response and the production of cytokines from the immune cells.

New probiotic microbe strains, such as Lactobacillus casei shirota (developed by Yakult USA Inc. for its cultured beverage shots), are pushing the envelope for the category beyond general immunity and cancer-protective effects through digestive health into strengthening the system in the presence of diseases, such as Crohn’s. They even can help with a healthy smile, via keeping oral in­­fections at bay.

While the study of probiotic bacteria and health can be said to be as old as fermented milk, bench science in recent years has made great strides in backing folklore. Often associated with digestive health, probiotics are showing much more complicated immune-support capacity, including abilities to protect against winter colds and flu viruses, lung infections, and even asthma and allergies. Moreover, when combined with prebiotic fibers, such as fructo-oliggosaccharides, they can form a powerful protective shield against some common ailments.

Two clinical studies by Mario Cazzola, M.D., and colleagues of the University of Rome and published in 2010 in Therapeutic Advances in Respiratory Disease, showed, among young children given three months of probiotic-prebiotic supplement, a significant reduction of common winter diseases (specifically ear-nose-throat, bronchopulmonary or gastric), compared to placebo. Additionally, 40% fewer children “missed at least one day of school.”

Other probiotic systems have even shown immune protection for oral health and secondary infections. Probiotic strains developed specifically to balance that “Grand Central Station of bacteria,” the oral cavity, have been proven to counter the proliferation of unfriendly bacteria that lead to sore throat, ear infection and other upper respiratory infections. Research has shown that a healthy balance of bacteria in the mouth helps provide protection from oral and dental pathogens to the gums and teeth. Probiotic systems have been developed to produce unique enzymes that dissolve plaque on the teeth and neutralize the harmful and corrosive acids it produces.

Plant-based Immunity

Botanicals and carbohydrate-derived ingredients play a great role in building humans up to battle the bugs. Flavonoids and phenolic compounds, such as hydroxytyrosol from olives, and resveratrol and quercetin from red and purple fruits (grapes, berries, black carrots, etc.), are now being studied for more than their potent antioxidant factors. They have shown strong anti-inflammatory response, as well as antiviral actions that could indicate a capacity for protection against a number of common elements, such as colds and flu.

Spices have enjoyed a multi-century connection to immunity, with the ones enjoying prominence in the pantry holding equally high prominence in the pantheon of ancient Ayurvedic and Chinese medicine. Clove, chili pepper, nutmeg and turmeric are proven, strong antimicrobial and antiviral botanicals. Cinnamon also has been the subject of multiple studies that found it can help regulate blood sugar, specifically lowering the fasting blood glucose levels in persons with type 2 diabetes.

Licorice root—Glycyrrhiza glabra—has a long tradition of use as an aid for easing problems of the respiratory system. Highly bioactive components called glycyrrhizin and glycyrrhetin have proven anti-inflammatory activity, and other studies point to glycyrrhizin being an antiviral agent in that capacity. Though well-studied, these compounds have only recently been investigated as possible immune ingredients for food and beverage applications because of the strong and unique flavor notes of licorice. But, technology has allowed them to be isolated in a more purified form that could open the door to expanded usage.

Another side of plant-based immunity involves particular carbohydrate compounds. Beta-glucans and resistant starch are two key ingredients for enhanced immunity seeing lots of time under the microscope of late. According to Stig Bengmark, M.D., Ph.D., in a 2002 article in Current Opinion in Critical Care, “Approximately 70% of the immune system is localized in the gastro­intestinal tract: its glands, mucosa and mucosa-associated lymphoid system.” Bengmark explains that the gastrointestinal tract influences physical well-being via secretions of health-supporting and disease-preventing chemical factors. Short-chain fatty acids (SCFAs), stimulated by resistent starch, are studied examples of such factors.

Brouns and Kettlitz of the Cerestar Vilvoorde Research & Development Centre in Havenstraat, Vilvoorde, Belgium; and Eva Arrigoni of the Institute of Food Technology and Food Science in Zurich, Switzerland, concluded that the SCFAs duo-propionate and butyrate “have the potential to support the maintenance of a healthy gut and to reduce risk factors that are involved in the development of gut inflammation” and cancer.

According to the researchers, this further supports the role of butyrate, also stimulated by resistant starch, in the role of proliferation and maintenance of healthy colon cells. In turn, it also contributes to the mechanism for “regeneration of the diseased lining of the gut.” They also described how butyrate inhibits proliferation of precancerous cells at “specific points of potential tumor development.”

Another aspect of resistant starch’s impact on immune function noted by the researchers is that RS-generated SCFAs  “have shown the potential to modify a number of metabolic actions and steps in the cell cycle in a way that early events in the cascade of cancer development may be counteracted while stages of progression may be slowed down.”

The Immune-Stress Response

“The link between stress, immune suppression and many health problems—from the common cold to accelerated disease progression and increased mortality—is well-documented,” notes Major General (ret) John Parker, M.D. As a former Assistant Surgeon General and Commanding General of the U. S. Army Medical Research and Materiel Command, Parker saw the toll chronic physical and psychological stress can have on health.

Among immune-support ingredients, beta-glucans—specifically beta-1,3/1,6 glucans—are clinically proven to help strengthen immunity and protect against stress-related health challenges that can suppress the immune system. Beta-glucans are a natural carbohydrate derived from select strains of baker’s yeast. Foods, beverages and supplements can easily incorporate and deliver immune health benefits with such a beta 1,3/1,6 glucan as a functional ingredient, meeting market demand in a wide range of options.

“In a 2010 survey of primary grocery shoppers, immune support was considered as the third-highest benefit sought in food and beverage products,” notes Parker. “A beta 1,3/1,6 glucan can be an elegant solution to ‘energize’ the immune system response in a way that is safe and natural. It primes neutrophils, the largest population of immune cells that are part of the body’s natural defenses.” Noting that some immune boosters or stimulators could be harmful in the long-term, he adds, “Specific beta 1,3/1,6 glucans support immune function without overstimulating the immune system.”

According to Parker, research has shown that slight differences in molecular structure of different beta 1,3/1,6 glucans can affect biological activity. Similar to probiotics, each product must be evaluated upon its own unique attributes and performance. He recommends use of beta-glucan ingredients supported by comprehensive research inclusive of individualized molecular characterization, and those describing a well-understood mechanism of action, as well as supported by peer-reviewed clinical research that consistently demonstrates the studied health benefit.

“It is important to understand that clinical results from one proprietary strain of yeast are not transferable to another,” stresses Parker. “Likewise, regulatory approvals, such as GRAS under U.S. FDA regulations, and approvals in other countries around the world are not transferable from one beta 1,3/1,6 glucan to another.” (Marketers should note that kosher, halal, non-allergenic and GMO-free designations all must be earned for each respective strain as well, as is true for other ingredient classifications.)

A number of recently published clinical trials involving human subjects have explored specific beta 1,3/1,6 glucans and immune function in relation to the reduction of immune suppression associated with physical and lifestyle stress. Studies in high-stress populations consistently found specific beta 1,3/1,6 glucans improved overall physical health and reduced the incidence—and in some cases, the duration—of upper respiratory tract infections (URTI) in comparison to the placebo group.

“Because people feel better psychologically when they feel better physically, the studies also included use of the Profile of Mood States (POMS) psychological survey instrument and found that the beta 1,3/1,6 glucan subjects reported feeling better about their overall health vs. the placebo group,” reports Parker. The POMS survey employs 65 adjective-based in­­dicators of mood, scaled for intensity (0-4); specific combinations of the adjectives define the six mood-state factors: tension, vigor, fatigue, confusion, anger and depression.

“The results of the rigorous studies are statistically significant and consistent with data from the other clinical studies demonstrating the ability of the specific strain studied to naturally enhance immune responses during periods of both high physical and psychological stress,” continues Parker.

In one 90-day Lifestyle Stress study, 122 healthy volunteers taking 250mg of the beta 1,3/1,6 glucan daily experienced a 58% decrease in URTIs. They rated their overall well-being and vigor 9.5% and 11% higher, respectively, compared with a placebo group. A High Lifestyle Stress study among 150 subjects found that, compared with the placebo group, after four weeks those taking 250mg of the ingredient experienced a 42% increase in vigor; a 38% reduction in fatigue; a 19% reduction in tension; and a 15% reduction in stress-induced confusion.

“In a clinical study among marathoners, the runners reported a 67% decrease in URTI symptoms. Subjects taking the ingredient also reported a 22% increase in vigor; a 48% reduction in fatigue; a 38% reduction in tension; and a 38% reduction in confusion vs. the placebo group. Among 100 fourth-year medical students—another population under extreme stress—in comparison with placebo subjects, those taking the ingredient significantly reduced (18%) the total duration of URTI symptoms (198 days vs. 241 days),” Parker says.

The totality of immune-boosting ingredients available to processors of foods, beverages and supplements can be overwhelming. By focusing on the class and subclass of the ingredient desired for a formulation, and the desired protective effect, manufacturers have at their disposal a much broader arsenal to engage against microbes, viruses, free oxygen radicals and even just plain aging that all keep consumers from engaging their peak performance abilities as they meet the increasing challenges of 21st century living.