I Feel Good: Ingredients and Immunity

By Kimberly J. Decker, Contributing Editor

Ten years ago, when Stuart Reeves, Ph.D., started examining the immune effects of products at Embria Health Sciences, he had a memorable exchange with an academic immunologist. She said, You know, youre going to find that immunologists are beginning to look at digestion and nutrition, and nutritionists are beginning to look at immunology, because they are a lot more linked than we thought they were," recalls the director of research and development at the Ankeny, IA, company. And she was absolutely right."

So linked are nutrition and immunity that the relationship has captured the attention of researchers, clinicians and the consuming public, whose interest has turned immune-enhancing foods and beverages into one of the fastest-growing sectors of the functional-food category. Manufacturers keen to get in on the action need grounding in the basics of immune function, and in the compounds and ingredients that help it function better.

All systems go

If Joe Consumer doesnt fully grasp immunitys intricacies, hes in good company. The scientific community is still teasing out immunitys mechanics. As the bodys defense against foreign invasion, the immune system is often likened to a castle whose moats, ramparts and battalions provide successive layers of defense. Barriers like skin and mucous membranes, as well as the cough reflex and enzymes in tears and sebum, provide  innate" immunity, a first line that acts without specificity against pathogens, antigens and other non-self" substances. Phagocytes called natural killer (NK) cells also rove the bloodstream, indiscriminately scavenging what they identify as foreign.

When the innate defenders fail, the next layer of immunity kicks in. This cell-based, or adaptive, response comprises the action of white blood cells known as B and T lymphocytes. The former produce antibodies that bind to antigens and ultimately destroy them, while the latter go after the antigens themselves, and also release cytokines that help control the immune response. In theory, this layered setup protects us from illness and infection. In practice, it often falls short or overreaches. Any number of culprits cause the immune response to fail, including genetics, pollution, oxidizing free radicals, aging and everyday stressors. Anything that stresses you stresses your immune system," says Cheryl Sturm, marketing director, Embria Health Sciences. Everybody deals with stress in a slightly different way. So every one of us has a personal immunity balance point."

Diet is crucial to striking this balance. Just eating a well-balanced diet of vegetables, fruits, whole grains and everything else were supposed to eat is the most-critical thing," says Kevin Mehring, global business director for dietary supplements and immune health, Danisco Health and Nutrition, Madison, WI.

The bottom line is that our gastrointestinal tract is a large immune organ," says Mehring. The gut mediates anywhere from 70% to 80% of immunity. Gastrointestinal mucosa, stomach acid and intestinal enzymes all participate in this interaction. But our natural gut florathe beneficial bacteria adapted to inhabit our gastrointestinal (GI) tracts and aid in digestionalso play a role.

Gut instincts

The microflora in your digestive system talk to your immune system," Reeves explains. Theres increasing work showing that the diet that you eat can change that microflorathe bacteriain your digestive system. And if you change the population, then you change the conversation." Consuming beneficial probiotics, including lactic acid bacteria and bifidobacteria, appears to turn that conversation in an immuno-positive direction.

Probiotics out-compete pathogens like Clostridium and E. coli for space and nutrition in the gut to grow. This lowers the incidence of illnessas does probiotics ability to alter gut pH to a level inhospitable to intruders. Probiotics also directly affect immune healthboth innate and adaptiveby triggering proliferation of the cells that produce immunoglobulin A (IgA), an important mucosal antibody, and of T cells and natural killer cells.

Probiotics have proven in clinical trials to reduce the number and duration of respiratory tract infections and dental caries in children, and are linked to the prevention of acute diarrhea in children and travelers diarrhea in adults. How they do this isnt entirely clear. We understand that when you take probiotics, you see changes in a few key biomarkers," notes Mehring. I think whats not understood is what is happening with probiotics on a very specific level to cause that change. The absolute mode of action is not as well understood as wed like it to be."

One thing we do understand is that probiotic benefits are strain-specific. Were talking about a microorganism that is a living being with a genetic makeup," Mehring says. What is it about this specific probiotic strain that makes it more likely to impact something like atopic eczema, versus another in the same genus and species that shows no impact, or maybe even a better impact?"

Consider Daniscos probiotic strains Lactobacillus rhamnosus HN001 and Bifidobacterium lactis HN019. There are multiple studies that have looked at these strains separately and in combination for the immune-related condition atopic eczema," Mehring says, and what they showed is that the HN001 had a very positive impact on lessening the severity in children, but the HN019 did not show a positive impact."

Similarly, Mike Bush, vice president, business development, Ganeden Biotech, Inc., Mayfield Heights, OH, notes that, though his company markets a number of probiotic strains closely related to its flagship Bacillus coagulans GBI30608, they do very different things," he says. They metabolize different carbohydrates very differently. They germinate at different temperatures. They produce different levels of lactic acid. So these are very closely related strains that have, in some cases, very different characteristics or mechanisms of action."

Finding an application and processing regimen that allows the probiotic cultures to survive is also key to producing a specific immune result. Typically, when were working with foods, were hoping that consumers, on a daily basis, can consume anywhere between 500 million and 2 billion CFU," Bush says. Those sound like huge numbers, but in the context of some probiotic-fortified products, where youre looking at 10 billion or maybe 50 billion CFU per day," he notes, theyre utterly achievable.The biggest threats to probiotics are pH, moisture and heat. Yogurt and fermented dairy products are preferred probiotic vehicles because they present an ideal environment for the cultures, and the cool storage conditions keep dormant cells from germinating before conditions are right. Youre putting something like cottage cheese, ice cream or yogurt in a refrigerator," Mehring says. So, in essence, youre controlling temperature all through the supply chain."

While refrigerated dairy is common, Bush notes his company has launched a probiotic-boosted tea, as well as muffins, bars and convenience foods. Their organism is a spore-former, so it is exceptionally heat, acid, bile and pressure tolerant," he says.

Feeding the troops

Probiotics need a steady source of nutrition to maintain their well-being. That nutrition source is a prebiotic, typically a fermentable soluble fiber.

While traditional dietary sources of prebiotic fibers include inulin, oats, soybeans, barley and other plant materials, some single out galactooligosaccharides (GOS) derived from dairy as the model prebiotic. According to Lorraine Niba, Ph.D., marketing manager, Americas, FrieslandCampina Domo, Paramus, NJ, GOS delivers a three-part package of immunity support. By serving as a fermentation substrate for probiotics, it encourages their proliferation in the colon. Secondly," she says, this increase in population helps inhibit adherence by pathogens to the colonic mucosa." Thirdly, by yielding short-chain fatty acids as a fermentation byproduct, GOS lowers colonic and fecal pH, further depleting pathogenic bacterial levels," she says.

One GOS, in powder and clear syrup forms, is designed for use in infant foods, beverages, dairy products, bakery products and nutritional bars. Its water-soluble at room temperature, and neither its structure nor its effectiveness is impacted by typical processing conditions such as heat or acid treatment," Niba says. Odorless and colorless with clarity in solution, its innocuous in most formulations, and 2.5 grams per serving suffice to qualify a product for a prebiotic claim.

Another prebiotic fiber gaining notice is larch arabinogalactan, or LAG, harvested from larch trees. LAG shores up immunity by feeding probiotic bacteria, serving as a source of the short-chain fatty-acid fermentation products that lower gut pH, and working directly on the immune system.

Brian Rodriguez, technical marketing and scientific affairs manager, Lonza Inc., Allendale, NJ, notes that pretreatment of human peripheral blood mononuclear cells with LAG correlates with enhancement of natural killer cell cytotoxicity, apparently through the action of cytokines. In cell culture," he explains, LAG induced an increased release of interferon gamma (IFN gamma), tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6). It was found that the IFN gamma was most responsible for the observed enhancement of NK cytotoxicity."

Lonza uses a water-extraction method to produce its LAG ingredient, notes Rodriguez. Its highly branched structure makes it readily soluble in hot or cold water, and it maintains stability over a wide temperature and pH range. The company processes the ingredient to minimize odor and flavor, and any remaining woody note," as he characterizes it, succumbs easily to flavor adjustment at typical use levels. (Studies suggest delivering 1.5 to 4.5 grams per day to achieve immune benefits.) The ingredient contains the polyphenolic flavonoids taxifolin and quercetin. These have been shown to display a wide range of biochemical properties, including antioxidant and chemoprotective effects," he says.

Oxidation detox

Oxidation weakens the bodys natural defenses, so its no surprise that protecting against oxidation strengthens immunity.

If you dont have enough oxidative protection," notes Ram Chaudhari, Ph.D., FACN, CNS, senior executive vice president and chief scientific officer, Fortitech, Inc., Schenectady, NY, then you deplete immune capacity and trigger inflammation, where cells are slowly going to give up their natural defense." He cites good, old-fashioned vitamins and minerals as bulwarks against that damage. Carotenoids, vitamin C and vitamin E improve the capacity of innate immune cells to fight off infection and goose the proliferation of T-cells. Vitamin D is a membrane antioxidant that boosts innate immunity and protects against bacterial infection, he adds. And the antioxidant minerals copper, zinc and selenium regulate redox-sensitive transcription factors, while also affecting cytokines. Physiological amounts of zinc have reduced morbidity and mortality associated with respiratory and diarrheal diseases in developing countries, he notes.

Many botanicals also demonstrate antioxidant and immunoprotective behavior. Grape-derived ingredients, such as extracts of seeds and skin, contain potent polyphenolic antioxidants and may exhibit antiviral and antibacterial properties. Grape seed proanthocyanidins may affect immune functions by increasing natural killer cell cytotoxicity and lymphocyte proliferation," notes Cecily Hawkins, associate scientist, H.I.T.S., Wild Flavors, Inc., Erlanger, KY. Studies show that green tea may increase lymphocyte proliferation, prevent inflammation and act against viruses and bacteria. Shiitake mushrooms are rich in beta-glucans that bind to lymphocyte surfaces and activate macrophages, T-helper cells, natural killer cells and other effector cells, she says. Shiitake may also increase production of IgA.

One patented blend of grape skin, grape seed, shiitake and green tea extracts standardized to 25% polyphenols and rich in antioxidant compounds protect the body from the damaging effects of free-radicals," Hawkins notes. Clinical testing shows the product reduces the duration and severity of symptoms associated with the common cold. Clinical studies settle on 1.76 grams, taken twice daily with 100 mg of vitamin C, as effective in reducing symptoms of the common cold. Depending on the application," she says, you can typically use the full dose per serving." Its a dry, water-soluble powder suited for use in enhanced waters, juices, smoothies, shots, bars and frozen treats, she says. Its process- and condition-stable, although it does contribute a dark-purple color and noticeable astringency to formulations.

Masking flavors can usually take care of the off notes, Hawkins says. Our flavor chemists have produced two new flavors that fit with the blends inherent taste profile," she says. One is a natural wild cherry flavor and the other is a natural Pinotage wine flavor."

Flame throwers

Among oxidations less-desirable side effects is inflammation. Yet inflammation is also a crucial step in the immune response. Inflammation, in the right place at the right time, is a definite good thing," Reeves says. Its a sign that the immune system is bringing everything to bear on a problem. If youve got a cold or flu, youre going to get inflammation in some of your nasal passages and your lungs, and this is the immune system doing what its supposed to do to fight off an infection."

Its when this inflammatory response goes into overdrive for no good reason that problems like allergies and autoimmune disorders result. Balance is key. Some foods and ingredients, and the compounds within them, help restore immunitys balance by modulating the inflammatory response. What the right natural product can do," Reeves says, is not attack the symptoms, but attack the root cause, which is this imbalance in the immune system."

One such product begins as bakers yeast (Saccharomyces cerevisiae), which undergoes aerobic fermentation during its growth. The yeast is added to a nutrient broth of proteins, fiber, vitamins, minerals and antioxidants, and the whole mix is subjected to a second, anaerobic fermentation. When yeast is deprived of oxygen," Sturm explains, it fights back by excreting metabolites. So we take that whole broth that has the beneficial parts of the yeast, the metabolites and all the nutrient content, and we dry the whole thing down to a very complex group of substances that actually becomes a single ingredient."

It affects an immune response, Reeves says, by altering the flow of information" to and from the immune cells lining the gut. And once you start interacting with those cells," he says, you can start changing the messages being sent." Human clinical trials showed that subjects taking the product had significantly fewer colds and cases of the flu, and those they had were of shorter duration. He attributes this to the products ability to boost levels of IgA. Theyve also linked the product to stimulation of natural killer cell and B cell activity.

In some of the work that weve done, weve actually shown that we can raise certain immune markers and suppress others in the same person at the same time," Sturm says. Thats what substantiates the balance claim."

The ingredient is heat-stable and has a three-year shelf life. The dried powder is dispersiblenot solublein beverages. At higher concentrations, it contributes a golden-brown hue to products, but in a tea or citrus drinkor in a baked goodthe effect would go unnoticed. GRAS in all foods and beverages at up to 3 grams, the ingredient has demonstrated effectiveness in adults at much lower dosesaround 500 mg, Sturm says.

Another yeast-derived immune balancer not only defends against outside invaders, it can be considered an immune modulatora compound that helps restore normal immune function, whether too high or too low," says Rich Mueller, president and CEO, Biothera, Eagan, MN. A gluco 1,3/1,6 polysaccharide harvested from the cell walls of a proprietary strain of yeast, the product works by activating immune cells called neutrophils to more quickly recognize and kill foreign intruders," he says. It does this without overstimulating the immune system.

The product is available in both soluble and dispersible forms. Mueller notes that both are stable to the heat, pH, chemical and pressure conditions typical to food and beverage processing, withstanding even UHT sterilization and retorting. A 200-mg daily dose, which can be incorporated into a typical 8-oz. beverage serving, demonstrates efficacy in most adults, he says.

Omega factor

Yeast fermentates arent the only ingredients that modulate inflammation associated with the immune response. The omega-3s docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), both long-chain polyunsaturated fatty acids (lc PUFAs), have a major influence on the immune system in that they are anti-inflammatory," notes James Elliott, Ph.D., director, nutrition science affairs, DSM Nutritional Products, Inc., Parsippany, NJ.

Our bodies metabolize DHA and EPA to messenger molecules called eicosanoids and lessen inflammation. Since many diseases, such as heart disease, have as their mechanism a constant state of inflammation," Elliott says, this is a protective mechanism that keeps the immune system in balance."

A high degree of unsaturation makes long-chain omega-3s readily oxidizable. In use, omega-3 lc PUFA oils should be handled to reduce exposure to oxygen as much as is practical," Elliott says. This means incorporating into foods and beverages without excessive aeration that would accelerate oxidation," he notes. Metal ions, such as those contained in salts or in water used for formulation or production, can also compromise stability. Many DHA and EPA producers formulate their ingredients with antioxidants to stanch oxidation, after first removing any oxidized lipids from the unprocessed oils. Food matrices that protect the omega-3s from exposure to air, and packaging that reduces oxygen permeability, also increase shelf life.

Manufacturing DHA and EPA from fish oils processed to eliminate the oxidized lipids, aldehydes and ketones that promote oxidation, off odors and off flavors optimize immune-effectiveness by removing objectionable molecules and stabilizing against further oxidation," says Elliot.

Anthony Palmieri, market segment head, DSM, says they outfit some of their dry omega-3 ingredients with a patented beadlet technology that protects micro-sized active particles in a water-soluble shell. These small particles can then be more readily absorbed," he says.

Diane Hnat, senior technical marketing manager, DSM, notes that manufacturers should remain cognizant of the GRAS levels approved for the intended use. The level of EPA to mitigate inflammation for any particular individual might be well above what can be dosed into a single serving of food," she says. As well, since PUFAs are macronutrients, not micronutrients, the impact not only on the taste of the finished product but their effects on texture are also important to note. Major reformulation of a product might be needed to emulsify the oil or rebalance the mouthfeel."

Thats a lot to keep in mind. But the bottom line for immune-enhancing productsindeed, for any food that claims a functional benefitis results. Unless consumers ultimately feel better themselvesor at least believe they dothey wont come back for a second serving.

Kimberly J. Decker, a California-based technical writer, has a B.S. in consumer food science with a minor in English from the University of California, Davis. She lives in the San Francisco Bay Area, where she enjoys eating and writing about food. You can reach her at [email protected].

Probiotic Appeal

Consumers clearly have immunity on the brain. With outbreaks of everything from SARS and swine flu to pertussis and food poisoning heating up headlines, one need only hint at the prospect of the next global pandemic to put people on the defensive. Food and beverage manufacturers are responding to increased consumer demand for products that deliver immune health benefits," says Rich Mueller, president and CEO, Biothera, Eagan, MN. We believe that media coverage of pandemics like West Nile virus, bird flu and H1N1 in recent years has played a major role in educating consumers about the importance of immune health to their overall health."

In fact, Mueller says, a 2008 survey by the International Food Information Council (IFIC), Washington, D.C., found that 87% of consumers have a current or future interest in products that improve immune-system function. In addition to the IFIC data," he continues, a 2009 Nestlé survey found that mothers identified immunity as the most-important benefit for their two- to five-year-olds." He also notes that a 2010 prediction from SPINS, Schaumburg, IL, was, The recent flu scare still weighs heavily on consumers minds and products that give the immune system an extra boost will continue to do well."

With health-care costs on the rise, the prospects for such products look even better. Getting sick exacts a heavy toll, and consumers wager that paying a little more upfront for a food or drink that can ward off sickness may shield them from paying a lot more in treatment and lost productivity later on. Cheryl Sturm, marketing director, Embria Health Sciences, Ankeny, IA, attributes this thinking to the trend toward prevention that were seeing." According to the Health and Wellness Trends database study from the Natural Marketing Institute, Harleysville, PA, consumers cite boosting the immune system as the No. 1 thing they can do to prevent illness. Not only do they feel good about that, but theyre buying into this prevention-over-treatment regimen," she says. They may not understand all the complexities of the immune system, but they know that keeping it healthy is something proactive that they can do."