Linda Ohr

Linda Milo Ohr

Strengthening the immune system has definitely been on my mind as of late. My preschooler has brought home four colds in the span of three months. A relative of mine was recently diagnosed with West Nile virus. And in addition to numerous flu reports, my son’s school has also reported cases of whooping cough and hand-foot-mouth disease.

Baby Yogurt is one of Horizon Organic’s products that contains fructooligosaccharides and promotes its health benefits.

Environmental factors, stress, and poor nutrition can compromise people’s immune system, making them more susceptible to various ailments, such as a cold or the flu. It is rare to find someone who actually enjoys being sick, so it seems natural that consumers would look for ways to stay healthy and strengthen their immune system.

Consumers are now finding an increasing number of immune-enhancing foods and supplements on store shelves. Cereal, tea, soup, and orange juice boast immune-enhancing properties. Consumers purchase these not only in hopes of preventing the onslaught of ailments, but also to lessen the duration of them as well.

Vitamins, minerals, fiber, and probiotics are some of the immune-enhancing ingredients found in these products. While exact mechanisms behind some of their benefits are unclear, research continues to uncover beneficial relationships between these and the immune system. With innovative ingredients such as these, formulators have an arsenal of immune-boosting ingredients to use in product development. Here is a look at some reported immune-enhancers.

Vitamins and Minerals
Vitamins C, E, zinc, and selenium are widely used in immune-enhancing products. Essentials Immunity Defense, an orange juice introduced by Tropicana, Bradenton, Fla., in early 2004, for example, contains all of these nutrients. A more recent product, ImmuneWise from Hain-Celestial, is a cereal that contains a mixture of whole grain oats, flakes and blueberries, and is fortified with vitamins C and E, selenium and green tea extract.

Vitamins C, E, selenium, and zinc are often used in immune-enhancing products because of their antioxidant properties. “Basically, these are all very powerful antioxidants, especially vitamin E and C,” says Ram Chaudhari, Sr. Executive Vice President and Chief Scientific Officer, Fortitech, Schenectady, N.Y. “They scavenge free radicals and improve the overall inflammatory aspect of a cell.” Stopping inflammation of the intestinal lining of the body is key to enhancing immunity, emphasizes Chaudhari. “Absorption of nutrients is hindered if the intestinal lining is inflamed. Proper nutrition leads to proper health.”

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Two recent studies have shown the immune benefits of vitamin E and selenium in humans. Vitamin E supplementation reduced the risk of upper respiratory tract infections in elderly residents of nursing homes (Meydani et al., 2004). Researchers gave nursing-home residents 200 IU of supplemental vitamin E or placebos daily for one year. According to the researchers, “significantly fewer persons in the vitamin E group contracted one or more respiratory tract infections.” Most of the benefits were related to a reduction in occurrences of the common cold.

Increased selenium intake was found to improve immune function in adults, according to research at the University of Liverpool and the Rowett Research Institute in the UK (Broome et al., 2004). Selenium supplements boosted the cellular immune response through an increased production of interferon gamma and other cytokines, an earlier peak T cell proliferation, and an increase in T helper cells, said researchers. They noted that their data indicated that when the body contains low levels of selenium, it could have impaired immune status and find it more difficult to combat viruses.

When using vitamin E, vitamin C, selenium or zinc, there are no specific intake levels set for immune benefits. “For vitamin E, we generally see levels of 200–300 IU. Vitamin C intake levels are around 100–150 mg in order to fight adverse conditions. These are generally accepted nontoxic levels,” says Chaudhari. “Zinc is around 15 mg and selenium around 40–50 micrograms. These levels seem to work very well and are widely used in food products.”

Probiotics
Yogurt and cultured drinks are the most common vehicles for probiotics and their immune-enhancing benefits. For example, Dannon’s DanActive™ is a cultured dairy drink that is touted to help naturally strengthen your body’s defense system.” The beverage contains Streptococcus thermophilus, Lactobacillus bulgaricus, and the company’s exclusive strain of Lactobacillus casei.

“Immune effects observed with probiotics include immune enhancing effects (better activation of immune function), down-regulation effects (as seen with reducing inflammation), and impact on maturation of immune cells leading to healthier programming of the immune system to discourage allergy development,” states Mary Ellen Sanders, consultant, Dairy & Food Culture Technologies, Centennial, Colo.

Sanders elaborates on the proposed mechanisms behind probiotics’ immune effects.

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• Immune activity enhancement. It appears that live bacteria, or in some cases bacterial components (ssDNA, cell walls) can specifically interact with immune sensing cells, resulting in a plethora of measured ex vivo activities, including increased activity of phagocytic cells, increased activity of tumor killing cells, increased levels of certain cytokines, and increases in pathogen-specific immunoglobulins.

• Reducing gut inflammation. It appears that probiotics can react with certain immune cells, which causes them to increase levels of certain anti-inflammatory cytokines (observed in animal models). Interestingly, different strains of probiotics behave differently in this regard.

• Improved programming of the immune system to a less allergic system. The hypothesis is that exposure early in life to the right types of microbes can help balance the Th1/Th2 ratios. A profile high in Th2 is correlated with allergies. Infants have high Th2 levels. Within the first 6 months of life, if proper development occurs, there is a shift to a Th1 profile. If this doesn’t occur, the infant is at higher risk of developing allergies. Exposure to microbes is apparently one trigger that causes this shift to occur.

“Recommended probiotic intake levels are the intake levels tested and found to have an effect,” stresses Sanders. “Since many studies don’t test different intake levels, we are stuck concluding that the effects are present with the levels tested, but we don’t know if lower levels are adequate. Some studies have shown dose dependency, others haven’t.”

Prebiotics
Inulin, oligofructose, and fructooligosaccharides (FOS), also known as prebiotics, benefit immunity as well. “The exact mechanisms are still unclear, however, human and animal studies have shown that inulin is able to boost the immune response of humans by decreasing severity and duration of disease, decreasing incidence of tumors, and working synergistically with certain vaccinations,” explains John Martin, Project Leader, Orafti Active Food Ingredients, Malvern, Pa. Research presented at a 2004 Orafti Research Conference showed that prebiotic supplementation with inulin in rats significantly increased the production of secretory IgA (immunoglobulins including antibodies) as well as reduced the numbers of tumors in the colon.

“The most notable research was conducted by Saavedra (2002) on 123 children, 4–24 months old, showing that oligofructose decreased the symptoms associated with diarrhea, medical visits associated with diarrhea, day-care absenteeism, episodes of cold symptoms, and need for antibiotics for respiratory illness,” says Martin. “Inulin and oligofructose blends have also been shown to significantly increase IgG antibody levels in humans after measles vaccination.”

Inulin is used extensively in many functional foods and dietary supplements as a method to promote a healthy immune system. Orafti offers Raftilose® and Raftiline®, short- and long-chain inulin, respectively. Raftilose®Synergy1 is a special combination of oligofructose and inulin which maximizes calcium absorption.

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A short-chain FOS (scFOS®), NutraFlora® (GTC Nutrition, Golden, Colo.) can currently be found in six dairy products promoting immune benefits. Horizon Organic, Longmont, Colo., offers yogurt for babies, children, and adults, as well as a fruit smoothie. Luv’n Baby Yogurt and Naturally Nutritious Yogurt from Mountain High, Englewood, Colo., are marketed for many health benefits including a strengthened immune system.

ScFOS fosters the growth of bacterial species that benefit health through their growth, activity, and metabolic products, says Linda Douglas, Scientific Affairs Manager, GTC Nutrition. “Perhaps the most interesting aspect of an immunefunction effect from including NutraFlora in the diet is an increase in immune structures called Peyer’s patches. Peyer’s patches reside in the gastrointestinal tract and contain specialized cells called intraepithelial lymphocytes (IEL). These structures, which are a part of the immune system, are known as gut-associated lymphoid tissue (GALT). The abundance of GALT and the amount of immunoglobulin secreted into the gastrointestinal system make the GI tract the largest immune-function organ in the body. The GALT is also important because it is the body’s primary interface to the outside world. When NutraFlora is provided in the diet, the number of Peyer’s patches increases. Further, the activity of the IELs, which decreases during Salmonella infection, is maintained.”

Douglas recommends a daily dose in the range of 3 g or more of NutraFlora for appropriate immune-system modulation. “We typically see dosages of approximately 1–5 g/serving, depending on the application.”

Arabinogalactan
Larch arabinogalactan, a natural compound found in the Larix genus of trees, has been shown to stimulate the human immune response in adults. “Arabinogalactan yields a non-specific response, increasing the front line defenders of the immune system. It supports the body’s natural immune system by increasing the number and/or activity of key cells involved in the immune response, specifically lymphocytes and monocytes, which are white blood cells,” explains Bryan Rodriguez, Applications Specialist, Larex, White Bear Lake, Minn. “These effects have been seen in in vitro, in vivo and ex vivo clinical designs.”

Rodriguez adds that once a cell becomes infected, arabinogalactan also has an effect on NK cell activity. This is the cell that destroys infected cells. “These results have been consistent across the six human clinical studies we have conducted to date. Generally, the benefits can be seen at an intake level of 1.5 g/day.”

A study conducted by Larex looked at the effects of arabinogalactan on 500 children age 3–12. The children drank arabinogalactan-fortifed beverages for 12 weeks. “We actually saw some trends with reduction in the duration of illness and the number of illnesses. Not only does this study show the effect of arabinogalactan, it also exhibits its ease of use,” says Rodriguez. The study had a greater than 90% completion rate, indicating that incorporation of arabinogalactan did not negatively affect the sensory characteristics of the beverage.

ImmunEnhancer™ AG, offered by Larex, is FDA approved as a direct food additive and GRAS affirmed. “It is not limited when it comes to applications, which can include soups, meal replacement bars, teas, and beverages,” says Lori Siegler, Marketing Manager. “ImmunEnhancer  can be formulated into hot or cold products. It is very stable and there are no issues with pH.”

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Oat Beta-Glucan
Beta-glucan was shown to speed up the immune response in research conducted at the Dept. of Surgery at Rhode Island Hospital and Brown University (Tsikitis et al., 2004). Work showed that beta-glucan enhanced the ability of certain human immune cells to navigate to the site of a bacterial infection.

According to the researchers, beta-glucan, provided by Biopolymer Engineering, Inc., Eagan, Minn., binds to receptors (CR3) on neutrophils, the most abundant type of innate immune cell in the body, and benefits the host defense in two ways. One is increased killing capacity of the neutrophils, and the other is migration or chemotaxis to the site of an infection or challenge. Neutrophils are attracted to the site of an infection by blood proteins called chemoattractants and are among the first cells of the body to respond to a challenge due to infection or injury.

“Priming the neutrophils with beta-glucan increases their ability to sense complement fragments emanating from the site of an infection,” said Jonathan Reichner, Associate Professor of Surgery at Rhode Island Hospital and Associate Director of the Pathobiology Graduate Program at Brown University. “As a result, beta-glucan helps neutrophils locate the bacterial mother lode within an infected tissue. This more rapid response to infection results in faster microbial clearance and healing.”

Botanicals
According to the American Botanical Council (ABC), there are a handful of herbs with proven safety that can help improve the body’s immune functions. These include echinacea, elderberry, and the Chinese herb andrographis.

Studies on echinacea indicate that it can diminish the symptoms and duration of colds and flu. ABC founder and Executive Director Mark Blumenthal notes that although some recent clinical trials on echinacea have not confirmed its effectiveness, others have. One recent Canadian clinical trial on an echinacea extract (Echinilin®, Natural Factors, Burnaby, British Columbia, Canada; sold in the U.S. as Echinamide™), showed that the herbal extract lowered respiratory tract symptoms in people with colds (Goel et al., 2004).

In a recent Norwegian study, scientists were able to demonstrate that patients receiving elderberry extract (Sambucol®, Razei Bar, Jerusalem, Israel) recovered from the flu four days earlier than patients in the control group (Zakay-Rones et al., 2004). The study revealed that the elderberry extract shortened the duration of flu types A and B by four days, in the randomized, double-blind, placebo-controlled study. Symptoms were also made less severe, with no significant side effects reported.

In addition to echinacea and elderberry, andrographis is an herb with pronounced benefits for the immune system, says Blumenthal. A recently published review of 11 clinical trials showed that andrographis is safe and effective in treating upper respiratory tract infections associated with colds and flus (Coon et al., 2004).

“Unfortunately,” adds Blumenthal, “despite its good record of being scientifically documented for its safety and benefits, it has not yet become popular in the United States, although it is available from a few manufacturers.”

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Colostrum
Colostrum is the first milk produced by the cow for her calf. It contains high levels of bioactive components, which are thought to be beneficial for the immune system. These include immunoglobulins, growth factors, and lactoferrin.

According to New Zealand-based Fonterra, the company has seen sales of colostrum rise significantly in key Asian markets, especially following the outbreak of severe acute respiratory syndrome (SARS).

Fonterra reported in 2003 that the SARS virus boosted Chinese market demand for colostrum by more than five times forecasted figures. Although colostrum has yet to be a mainstream ingredient in the U.S., it is popping up in products outside of Asia. In early 2004, for example, Bomba, an Austrian energy drink maker, introduced SOL(e)UTION, a soft drink made of natural juices and enriched with colostrum.

New Immunity Ingredient
A new ingredient benefiting immunity was introduced at the IFT Food Expo® last year. OptiNutrin™, offered by NutraGenesis, Brattleboro, Vt., is a proprietary glucan protein complex. The ingredient is being marketed under a strategic alliance with Flavor & Fragrance Specialties, a Mahwah, N.J.–based flavor company.

According to NutraGenesis President, Suzanne McNeary, GRAS-affirmed OptiNutrin has been substantiated to support healthy immune function for good health and well-being. She explains that the ingredient stimulates various aspects of cellular immunity, mainly by increasing macrophage activity.

“There is a significant amount of peer-reviewed science on the therapeutic effects, in particular the immunopotentiating benefits of the active ingredients found in OptiNutrin. A lot of the research that has been done on the biologically active polysaccharides and glucan-protein complexes such as those found in OptiNutrin focuses on these compounds being able to enhance or potentiate host resistance by stimulating the immune system, which may result in a variety of therapeutic effects.”

The suggested daily usage level for OptiNutrin is 5–10 mg/day. For food or beverage products where the consumer is likely to consume multiple servings in the course of a day, the suggested daily usage range may be distributed over several servings.

The ingredient is virtually odorless and flavorless at the suggested dosage levels, as well as being water soluble and heat stable, making the product suitable for a variety of hot and cold beverages such as bottled waters and juices, cereals, baked goods, bars, confections, and meal replacements. McNeary states that OptiNutrin can be declared as a natural flavor in the ingredients panel or as mushroom extract.

The immunity market is entering exciting times. It is still a young area with potential for growth. These ingredients stand to help boost one’s immunity. Here’s to a healthy 2005!

by LINDA MILO OHR
Contributing Editor, Chicago, Ill.
[email protected]

About the Author

Linda Milo Ohr, Contributing Editor, Nutraceuticals column
[email protected]
Linda Ohr

References

Broome, C.S., McArdle, F., Kyle, J.A.M., Andrews, F., Lowe, N.M., Hart, C.A., Arthur, J.R., and Jackson, M.J. 2004. An increase in selenium intake improves immune function and poliovirus handling in adults with marginal selenium status. Am. J. Clin. Nutr. 80: 154-162.

Coon J.T. and Ernst, E. 2004. Andrographis paniculata in the treatment of upper respiratory tract infections: A systematic review of safety and efficacy. Planta Medica. 70: 293-296.

Goel, V., Lovlin, R., Barton, R., Lyon, M.R., Bauer, R., Lee, T.D., and Basu, T.K. 2004. Efficacy of a standardized Echinacea preparation (Echinilin™) for the treatment of the common cold: a randomized, double-blind, placebo-controlled trial. J. Clin. Pharm. Ther. 29: 75-83.

Meydani, S.N., Leka, L.S., Fine, B.C., Dallal, G.E., Keusch, G.T., Singh, M.F., and Hamer, D.H. 2004. Vitamin E and respiratory tract infections in elderly nursing home residents. A randomized controlled trial. J. Am. Med. Assn. 292: 828-836.

Tsikitis, V.L., Albina, J.E., and Reichner, J.S. 2004. Beta-glucan affects leukocyte navigation in a complex chemotactic gradient. Surgery 136: 384-389.

Zakay-Rones, Z., Thom, E., Wollan, T., and Wadstein, J. 2004. Randomized study of the efficacy and safety of oral elderberry extract in the treatment of influenza A and B virus infections. J. Intl. Med. Res. 32: 132-140.