Sean Moloughney11.01.08
As the human immune system confronts more environmental toxins and stressors today than in years past, consumers are looking for safe, simple and effective ways to support the body's natural defenses and prevent illness.
With more than 36,000 U.S. deaths and 200,000 hospitalizations attributed to influenza each year, direct and indirect costs of the average flu season amount to approximately $10 billion. The World Bank estimated that a severe influenza pandemic would cost the U.S. more than $600 billion, potentially leading to a major global recession.
Many experts believe the world is closer to such a pandemic today than at any other time since 1968, which witnessed the last of the previous century's three major outbreaks. Vaccination has been the primary means of prevention, but the market for natural ingredients is showing healthy development.
"The Natural Marketing Institute's (Harleysville, PA) 2008 Health & Wellness Trends Report indicates that immune health ranks near the top in both consumer interest and purchasing activity-both in natural and mass-market channels," said Cheryl Sturm, director of marketing, Embria Health Sciences, Ankeny, IA. "This across-the-board acceptance of, and demand for, immune products is no surprise."
The growing, perceived need for these products is due in part to an increasing prevalence of autoimmune diseases and consumer need to alleviate stress. About 87% of people say they already consume or are interested in consuming foods and beverages that improve immune system function, according to the International Food Information Council Foundation 2008 Food & Health Survey.
But do products live up to their hype? And which ingredients are actually backed by valid clinical data?
Of late, government and consumer groups have begun targeting companies that make dubious claims on products related to immune support. Airborne and its creator, second-grade teacher Victoria Knight McDowell, have taught the industry a valuable lesson. Touting a lone-and later-learned bogus-clinical trial, Airborne's effervescent health formula, which contains vitamins A and C, zinc and selenium, promised to "boost your immune system to help your body combat germs."
The Bonita Springs, FL-based company got a boost of its own following an appearance on the "Oprah Winfrey Show" as word of mouth spread across the U.S. But the public soon learned the company's trial was actually conducted without any doctors or scientists. Facing FTC investigation and class action lawsuits, Airborne agreed to pay back $30 million to consumers who made as many as six product purchases.
According to David Law, president and CEO, Gourmet Mushrooms, Sebastopol CA, "Airborne had been too aggressive in blurring the line between health foods and drugs. Some health food products in the market do have data examining ex vivo immune responses and anecdotal evidence. But companies should be careful not to market a health food product as a drug."
The Center for Science in the Public Interest (CSPI) also urged FDA in July to halt structure/function claims on food labels, citing products such as Kraft's Crystal Light Immunity Berry Pomegranate, which claims that its vitamins A, C and E will help "maintain a healthy immune system."
In its complaint, the nonprofit nutrition watchdog also referenced Green Giant Immunity Boost, a General Mills product, which contains frozen broccoli, carrots, pepper strips and seasoning. According to CSPI, "While it's a perfectly healthy food, there is no evidence to support the claim that the product 'supports a healthy immune system,' or provides the promised 'immunity boost.'" Additionally, CSPI highlighted products from Dole, Minute Maid, Sunsweet and Welch's as touting unrealistic claims.
Rich Mueller, president and CEO of Eagan, MN-based Biothera, said it's true that while some major companies have recognized the potential of this market, they haven't completely followed through. "The problem in the industry that's emerging is a lot of companies are jumping on this opportunity without changing their product, or putting ingredients in their product that actually boost the immune system. And consumer groups are taking them to task for that."
Valid clinical research then becomes critical for the future of the immune support market. Biothera, a biotechnology company, manufactures Wellmune WGP, a GRAS (Generally Recognized as Safe) yeast-based (beta-glucan) ingredient. The company has compiled several studies-published in peer-reviewed journals-that support its efficacy.
According to Don Cox, PhD, vice president of research and development with Biothera, Wellmune WGP primes key immune cells, including macrophages and neutrophils (types of white blood cells), to quickly identify and kill foreign challenges. The product engages the body's natural defenses to promote health, wellness and vitality, he said.
In a single-blind, random, crossover study, 54 firefighters were given Wellmune WGP or placebo for 14 days, followed by a three-day washout period and another 14-day treatment period. Results indicated a strong statistical trend favoring the use of Wellmune WGP for the prevention of upper respiratory tract infections (URTI), as 48% of the firefighters experienced URTI while taking the placebo, compared to only 37% for the Wellmune group.
In another double-blind, placebo-controlled study conducted during the cold season, 40 healthy subjects, ages 18 to 65, were treated daily with either 250 mg of Wellmune WGP or a placebo for 90 days. Those who received Wellmune WGP reported: no incidence of medically verified fever; an increase in general health markers, including physical energy and emotional well-being; and no need to take a "sick day" off of work or school.
With two other recent studies demonstrating Wellmune's effectiveness in dealing with stress-related health challenges, such as mental and physical fatigue, Mr. Cox, said, "We're building a compelling picture that our ingredient supports the immune system, and maintains and improves overall physical health."
"We have a unique opportunity to impact immune health from the nutritional intervention perspective," he added. "Whether used as a supplement or in food or beverages, we can work on preventing a problem before it occurs."
Embria Health Sciences has also compiled substantial clinical evidence supporting its GRAS ingredient EpiCor, a complex yeast fermentate, created through a proprietary process.
One recent study published in the online, peer-reviewed Open Nutrition Journal, showed that EpiCor supports the formation of healthy red blood cells, while also supporting mucosal defense and anti-inflammatory activity. For this study, 25 healthy participants received 500 mg of EpiCor or placebo for five weeks. Results showed an increase in the volume of red blood cells, as well as a mild increase in secretory immunoglobulin A (sIgA), an antibody that protects mucosal surfaces from pathogens. Participants taking EpiCor also showed an increase in levels of the anti-inflammatory cytokine interleukin-10 (IL-10).
Previous studies have also shown EpiCor's positive impact on the immune system, including a double-blind, placebo-controlled human trial involving 232 subjects during the winter flu season in the Midwest. Participants received 500 mg of the supplement and researchers measured incidence and severity of URTIs. Compared to placebo, the EpiCor supplemented group showed a reduction in incidence of 21% and duration of 14%.
Overall, many companies have been cautious when making claims on specific areas of health, according to Trina O'Brien, marketing and public relations manager at GTC Nutrition, Golden, CO. Still, many manufacturers are finding a path to immune support-through the stomach.
"Prebiotic fiber ingredients, such as GTC's NutraFlora short-chain fructooligosaccharides (scFOS), are often incorporated into products touting immune health claims," Ms. O'Brien stated. "Prebiotics are uniquely able to fuel the growth of beneficial microflora, which naturally help boost the body's defenses."
In tandem with prebiotics, researchers have conducted comprehensive analyses on probiotics and their effect on immunity. "Probiotics are more important than multi-vitamins and should be taken daily," said Dr. S.K. Dash, president, UAS Laboratories, Eden Prairie, MN. "But all probiotics are not the same."
UAS has 40 years of research to support the superiority of its super strain L. acidophilus DDS-1 and DDS-Probiotics, he said. Its most recent study, conducted at the National Medical University in Ukraine, showed an increase in the intensity of intestinal lipid peroxidation, suggesting the role of probiotic bacteria in maintaining immune and intestinal pro- and anti-inflammatory control.
Tim Gamble, vice president, Sales and Marketing, Nutraceutix, Inc., Redmond, WA, said research involving his company's Immunobiotix probiotic tablets demonstrates the product's ability to enhance phagocytosis (the process by which a cell engulfs foreign matter) by supporting monocytes and neutrophils. The tablets include a proprietary blend of natural probiotic organisms and incorporate the company's patent-pending BIOtract technology, which delivers live organisms past harsh stomach acids and into the intestinal tract.
Ganeden Biotech, Mayfield Heights, OH, also supplies its custom probiotic GanedenBC30, and works with customers "to ensure their labeling claims are backed by our science," said Julia Boyd, business development coordinator with Ganeden.
"There is a growing body of evidence to suggest that many immune disorders and allergies are caused by imbalances in the intestinal microflora," Ms. Boyd noted. "With additional research, it may be possible to address these issues."
Isabelle Champi, human nutrition brand manager for Institut Rosell-Lallemand, Montreal, Quebec, Canada, said her company has focused its research on the expression of selected probiotic strains on cytokines, which play a central role in the immune system as chemical messengers between cells.
One study involving an animal model of bacterial infection (E. coli challenge in rats) showed that two-week preventive treatment with the company's ProbioKid formula (a synbiotic formula combining FOS and the probiotic strains Lactobacillus Rosell-52, Bifidobacteria Rosell-71 and Bifidobacteria Rosell-33) significantly affected the animals' health and immune status. "Weight loss following E. coli infection was decreased as compared to control, showing improved resistance against infection," she said. "Levels of pro-inflammatory cytokines decreased while anti-inflammatory levels increased."
Staying in the stomach, colostrum is another promising ingredient that has been used to balance intestinal microflora. Mothers produce colostrum during the first few days after giving birth. It is rich in antibodies and lactoferrin, as well as immunoglobulins, insulin-like growth factor (IGF) and transforming growth factor (TGF). Bovine colostrum-based immune milk products have demonstrated effectiveness in targeting infectious diseases.
At odds with increased consumption of probiotics, is what many view as the overuse of antibiotics. Studies suggest that half of the estimated 100 million antibiotic prescriptions written for respiratory tract infections in the U.S. are unnecessary. Bad reactions to antibiotics, mostly allergic ones, send people to U.S. emergency rooms more than 140,000 times each year, according to a government team at the Centers for Disease Control and Prevention (CDC).
According to Brien Quirk, technical director, Draco Natural Products, San Jose, CA, doctors and patients have recognized the overuse of antibiotics, which is "causing the development of very scary disease-resistant organisms like Methicillin-Resistant Staphylococcus aureus (MRSA) and H157 E. coli, for which few remaining, heavy-hitting and toxic antibiotics are left."
"The narrow action of most antibiotics, combined with the increasing problems of bacterial resistance does not leave the pharmaceutical industry strong in this area," said Gitte Jensen, PhD, research director, with Klamath Falls, OR-based NIS Labs, a contract research lab that focuses on natural products and their role in immune support. "There is huge potential for a large number of natural products that may have broader mechanisms of action, such as direct anti-bacterial effects, combined with support of innate immune mechanisms."
NIS Labs has solidified a number of research protocols pertaining to the testing of anti-inflammatory properties of natural products, according to Dr. Jensen. "We have developed a panel of in vitro testing of the migratory behavior of inflammatory polymorphonuclear (PMN) cells from human blood samples. We conduct a complex test panel, where we examine the spontaneous migratory behavior of the PMN cells, which reflects one aspect of immune surveillance. In parallel, we also examine altered migratory behavior in response to bacterial presence, versus inflammatory mediators produced by the body itself."
She noted that, at times, products might positively support immune surveillance but also inhibit migration in response to inflammatory mediators. "This may help suggest that a product, when consumed, may support normal immune defense mechanisms, but inhibit parts of an inflammatory cascade," she said. Overall, "The natural products industry must tread wisely; claims must be backed by proper research," she advised.
Lonza, Allendale, NJ, recently launched ResistAid, an all-natural, multifunctional product that contains the soluble polysaccharide arabinogalactan and bioactive flavonoids derived from larch tress. According to Bryan Rodriguez, technical marketing and scientific affairs manager at Lonza, larch arabinogalactan's mechanisms of action include effects on lactic acid-producing bacteria or bacterial constituents on immune cells, the production of short chain fatty acids (SCFA) and binding to SCFA receptors on leucocytes, but also direct effects on components of the immune system.
Interestingly, Mr. Rodriguez noted, several "immune-enhancing" herbs contain significant amounts of arabinogalactan, such as Echinacea purpurea, Baptisia tinctoria or Thuja occidentalis, and researchers speculate this is one of the main immune-activating principles in these herbs.
For years echinacea has been widely used as a supplement for immune health. "Echinacea has good studies for respiratory tract infections like bronchitis associated with the common cold in children," said Draco's Mr. Quirk. "The public still perceives echinacea to be helpful for the common cold even though the mainstream media has cast doubt with some poorly designed negative studies using lower than normal dosages of unapproved preparations."
Meanwhile, newer ingredients are emerging on the scene. Nick Falk, business development director, Marinova Pty Ltd, a biotechnology company based in Cambridge, Australia, said researchers recently completed a two-arm open label pilot study of the company's Marinova Extract, a fucoidan and polyphenol rich seaweed extract. The study involved five healthy patients, who received 100 mg (clinical dose) or 1000 mg (safety test dose) of Maritech Extract.
The study compared baseline in vivo and ex vivo changes of antioxidant levels and various immune cell functions over a four-week period. In the short-term (three days) the extract caused a spike in immune cell activity, specifically for B Cells (CD19), cytotoxic T cells, monocytes and natural killer cells. In the long-term (daily dose for 28 days) activity levels of monocytes and granulocytes increased significantly.
"There are very few ingredients that have been able to demonstrate both short-term and long-term effectiveness," said Mr. Falk. "It's very strong immune data." Results are expected to be published this year in the peer-reviewed journal Alternative and Complementary Medicine.
Looking at the broader picture, many experts have acknowledged a rise in prevalence of immune disorders. Gourmet Mushrooms' Mr. Law said the proliferation of novel industrial molecules from pesticides, plastics, food additives and other compounds has contributed to such an increase. "The pro-inflammatory and anti-inflammatory functions of our immune cells are off balance due to constant environmental assaults," he said.
Immune support has been one of the key selling points for mushrooms, according to Mr. Law, and his company emphasizes the use of its products in the modulation of internal cellular communications.
"Mushroom extracts are botanicals with strong consumer awareness for immune health since there is ample research and actual applications in countries like Japan, South Korea and China," said Draco's Mr. Quirk.
Recent research published on Active Hexose Correlated Compound (AHCC), an ingredient derived from the hybridization of several subspecies of medicinal mushrooms, shows it may stimulate the immune system and help the body respond to a broad spectrum of infectious threats. AHCC is manufactured by Amino Up Chemical Company in Sapporo, Japan and distributed in the U.S. by Maypro Industries, which sells AHCC to several leading supplement companies, including Quality of Life Laboratories, a subsidiary of Maypro.
The scientific review analyzed outcomes from in vivo studies and reported that AHCC activates important immune white blood cells, including macrophages, natural killer cells and lymphokine activated killer (LAK) cells following foreign challenges such as influenza virus, avian influenza (bird flu), MRSA, Klebsiella pnuemoniae and Candida albicans. Ongoing research is examining AHCC's ability to impact T cells related to cellular immunity and determining if AHCC supplementation can serve as a beneficial vaccine adjuvant for the flu shot.
In addition to the overuse of antibiotics and rising environmental toxicity, Steve Siegel, Ecuadorian Rainforest, LLC, Belleville, NJ, said poor nutrition and increasingly stressful, on-the-go lifestyles play significant roles in diminishing the immune system's effectiveness. "Individuals wishing to live a healthy lifestyle should incorporate a variety of fruits and vegetables into their daily diet," he said. "Ecuadorian Rainforest supplies a colorful variety of ingredients derived from 'whole food' sources to meet these demands."
The company offers a range of products that contain optimal amounts of vitamin A, which has been shown to fight off infections, according to Mr. Siegel. Ecuadorian also supplies vitamin C-rich foods. "Vitamin C has been shown to support a healthy immune system by assisting the body's natural ability to heal itself," he noted.
Alongside efficacy, safety will continue to be a critical market factor. For example, Canada's number one selling cold and flu remedy, COLD-fX-derived from North American ginseng-from CV Technologies, Edmonton, Alberta, Canada, is currently intended for adults and children 12 years of age and older. But a recent randomized, double-blind, placebo-controlled study published in the journal Pediatrics demonstrated its safety in younger children too. Of 75 children recruited for this trial (ages 3 to 12), 46 developed a URTI and were assigned to receive acute three-day treatments with either placebo or COLD-fX. Both were well tolerated with no significant adverse reactions.
Ironically, these findings come at a time when drug companies that make non-prescription cold and cough medicines say they will stop marketing over-the-counter drugs to children under the age of 4. This pledge recently coincided with an extensive federal review of whether the drugs are safe and effective for children under 12. Americans spend an estimated $300 million on non-prescription children's cold remedies every year.
With more than 36,000 U.S. deaths and 200,000 hospitalizations attributed to influenza each year, direct and indirect costs of the average flu season amount to approximately $10 billion. The World Bank estimated that a severe influenza pandemic would cost the U.S. more than $600 billion, potentially leading to a major global recession.
Many experts believe the world is closer to such a pandemic today than at any other time since 1968, which witnessed the last of the previous century's three major outbreaks. Vaccination has been the primary means of prevention, but the market for natural ingredients is showing healthy development.
"The Natural Marketing Institute's (Harleysville, PA) 2008 Health & Wellness Trends Report indicates that immune health ranks near the top in both consumer interest and purchasing activity-both in natural and mass-market channels," said Cheryl Sturm, director of marketing, Embria Health Sciences, Ankeny, IA. "This across-the-board acceptance of, and demand for, immune products is no surprise."
The growing, perceived need for these products is due in part to an increasing prevalence of autoimmune diseases and consumer need to alleviate stress. About 87% of people say they already consume or are interested in consuming foods and beverages that improve immune system function, according to the International Food Information Council Foundation 2008 Food & Health Survey.
But do products live up to their hype? And which ingredients are actually backed by valid clinical data?
Claims in Question
Of late, government and consumer groups have begun targeting companies that make dubious claims on products related to immune support. Airborne and its creator, second-grade teacher Victoria Knight McDowell, have taught the industry a valuable lesson. Touting a lone-and later-learned bogus-clinical trial, Airborne's effervescent health formula, which contains vitamins A and C, zinc and selenium, promised to "boost your immune system to help your body combat germs."
The Bonita Springs, FL-based company got a boost of its own following an appearance on the "Oprah Winfrey Show" as word of mouth spread across the U.S. But the public soon learned the company's trial was actually conducted without any doctors or scientists. Facing FTC investigation and class action lawsuits, Airborne agreed to pay back $30 million to consumers who made as many as six product purchases.
According to David Law, president and CEO, Gourmet Mushrooms, Sebastopol CA, "Airborne had been too aggressive in blurring the line between health foods and drugs. Some health food products in the market do have data examining ex vivo immune responses and anecdotal evidence. But companies should be careful not to market a health food product as a drug."
The Center for Science in the Public Interest (CSPI) also urged FDA in July to halt structure/function claims on food labels, citing products such as Kraft's Crystal Light Immunity Berry Pomegranate, which claims that its vitamins A, C and E will help "maintain a healthy immune system."
In its complaint, the nonprofit nutrition watchdog also referenced Green Giant Immunity Boost, a General Mills product, which contains frozen broccoli, carrots, pepper strips and seasoning. According to CSPI, "While it's a perfectly healthy food, there is no evidence to support the claim that the product 'supports a healthy immune system,' or provides the promised 'immunity boost.'" Additionally, CSPI highlighted products from Dole, Minute Maid, Sunsweet and Welch's as touting unrealistic claims.
Rich Mueller, president and CEO of Eagan, MN-based Biothera, said it's true that while some major companies have recognized the potential of this market, they haven't completely followed through. "The problem in the industry that's emerging is a lot of companies are jumping on this opportunity without changing their product, or putting ingredients in their product that actually boost the immune system. And consumer groups are taking them to task for that."
Yeast's Rising Importance
Valid clinical research then becomes critical for the future of the immune support market. Biothera, a biotechnology company, manufactures Wellmune WGP, a GRAS (Generally Recognized as Safe) yeast-based (beta-glucan) ingredient. The company has compiled several studies-published in peer-reviewed journals-that support its efficacy.
According to Don Cox, PhD, vice president of research and development with Biothera, Wellmune WGP primes key immune cells, including macrophages and neutrophils (types of white blood cells), to quickly identify and kill foreign challenges. The product engages the body's natural defenses to promote health, wellness and vitality, he said.
In a single-blind, random, crossover study, 54 firefighters were given Wellmune WGP or placebo for 14 days, followed by a three-day washout period and another 14-day treatment period. Results indicated a strong statistical trend favoring the use of Wellmune WGP for the prevention of upper respiratory tract infections (URTI), as 48% of the firefighters experienced URTI while taking the placebo, compared to only 37% for the Wellmune group.
In another double-blind, placebo-controlled study conducted during the cold season, 40 healthy subjects, ages 18 to 65, were treated daily with either 250 mg of Wellmune WGP or a placebo for 90 days. Those who received Wellmune WGP reported: no incidence of medically verified fever; an increase in general health markers, including physical energy and emotional well-being; and no need to take a "sick day" off of work or school.
With two other recent studies demonstrating Wellmune's effectiveness in dealing with stress-related health challenges, such as mental and physical fatigue, Mr. Cox, said, "We're building a compelling picture that our ingredient supports the immune system, and maintains and improves overall physical health."
"We have a unique opportunity to impact immune health from the nutritional intervention perspective," he added. "Whether used as a supplement or in food or beverages, we can work on preventing a problem before it occurs."
Embria Health Sciences has also compiled substantial clinical evidence supporting its GRAS ingredient EpiCor, a complex yeast fermentate, created through a proprietary process.
One recent study published in the online, peer-reviewed Open Nutrition Journal, showed that EpiCor supports the formation of healthy red blood cells, while also supporting mucosal defense and anti-inflammatory activity. For this study, 25 healthy participants received 500 mg of EpiCor or placebo for five weeks. Results showed an increase in the volume of red blood cells, as well as a mild increase in secretory immunoglobulin A (sIgA), an antibody that protects mucosal surfaces from pathogens. Participants taking EpiCor also showed an increase in levels of the anti-inflammatory cytokine interleukin-10 (IL-10).
Previous studies have also shown EpiCor's positive impact on the immune system, including a double-blind, placebo-controlled human trial involving 232 subjects during the winter flu season in the Midwest. Participants received 500 mg of the supplement and researchers measured incidence and severity of URTIs. Compared to placebo, the EpiCor supplemented group showed a reduction in incidence of 21% and duration of 14%.
Probiotics
Overall, many companies have been cautious when making claims on specific areas of health, according to Trina O'Brien, marketing and public relations manager at GTC Nutrition, Golden, CO. Still, many manufacturers are finding a path to immune support-through the stomach.
"Prebiotic fiber ingredients, such as GTC's NutraFlora short-chain fructooligosaccharides (scFOS), are often incorporated into products touting immune health claims," Ms. O'Brien stated. "Prebiotics are uniquely able to fuel the growth of beneficial microflora, which naturally help boost the body's defenses."
In tandem with prebiotics, researchers have conducted comprehensive analyses on probiotics and their effect on immunity. "Probiotics are more important than multi-vitamins and should be taken daily," said Dr. S.K. Dash, president, UAS Laboratories, Eden Prairie, MN. "But all probiotics are not the same."
UAS has 40 years of research to support the superiority of its super strain L. acidophilus DDS-1 and DDS-Probiotics, he said. Its most recent study, conducted at the National Medical University in Ukraine, showed an increase in the intensity of intestinal lipid peroxidation, suggesting the role of probiotic bacteria in maintaining immune and intestinal pro- and anti-inflammatory control.
Tim Gamble, vice president, Sales and Marketing, Nutraceutix, Inc., Redmond, WA, said research involving his company's Immunobiotix probiotic tablets demonstrates the product's ability to enhance phagocytosis (the process by which a cell engulfs foreign matter) by supporting monocytes and neutrophils. The tablets include a proprietary blend of natural probiotic organisms and incorporate the company's patent-pending BIOtract technology, which delivers live organisms past harsh stomach acids and into the intestinal tract.
Ganeden Biotech, Mayfield Heights, OH, also supplies its custom probiotic GanedenBC30, and works with customers "to ensure their labeling claims are backed by our science," said Julia Boyd, business development coordinator with Ganeden.
"There is a growing body of evidence to suggest that many immune disorders and allergies are caused by imbalances in the intestinal microflora," Ms. Boyd noted. "With additional research, it may be possible to address these issues."
Isabelle Champi, human nutrition brand manager for Institut Rosell-Lallemand, Montreal, Quebec, Canada, said her company has focused its research on the expression of selected probiotic strains on cytokines, which play a central role in the immune system as chemical messengers between cells.
One study involving an animal model of bacterial infection (E. coli challenge in rats) showed that two-week preventive treatment with the company's ProbioKid formula (a synbiotic formula combining FOS and the probiotic strains Lactobacillus Rosell-52, Bifidobacteria Rosell-71 and Bifidobacteria Rosell-33) significantly affected the animals' health and immune status. "Weight loss following E. coli infection was decreased as compared to control, showing improved resistance against infection," she said. "Levels of pro-inflammatory cytokines decreased while anti-inflammatory levels increased."
Staying in the stomach, colostrum is another promising ingredient that has been used to balance intestinal microflora. Mothers produce colostrum during the first few days after giving birth. It is rich in antibodies and lactoferrin, as well as immunoglobulins, insulin-like growth factor (IGF) and transforming growth factor (TGF). Bovine colostrum-based immune milk products have demonstrated effectiveness in targeting infectious diseases.
Antibiotics
At odds with increased consumption of probiotics, is what many view as the overuse of antibiotics. Studies suggest that half of the estimated 100 million antibiotic prescriptions written for respiratory tract infections in the U.S. are unnecessary. Bad reactions to antibiotics, mostly allergic ones, send people to U.S. emergency rooms more than 140,000 times each year, according to a government team at the Centers for Disease Control and Prevention (CDC).
According to Brien Quirk, technical director, Draco Natural Products, San Jose, CA, doctors and patients have recognized the overuse of antibiotics, which is "causing the development of very scary disease-resistant organisms like Methicillin-Resistant Staphylococcus aureus (MRSA) and H157 E. coli, for which few remaining, heavy-hitting and toxic antibiotics are left."
"The narrow action of most antibiotics, combined with the increasing problems of bacterial resistance does not leave the pharmaceutical industry strong in this area," said Gitte Jensen, PhD, research director, with Klamath Falls, OR-based NIS Labs, a contract research lab that focuses on natural products and their role in immune support. "There is huge potential for a large number of natural products that may have broader mechanisms of action, such as direct anti-bacterial effects, combined with support of innate immune mechanisms."
NIS Labs has solidified a number of research protocols pertaining to the testing of anti-inflammatory properties of natural products, according to Dr. Jensen. "We have developed a panel of in vitro testing of the migratory behavior of inflammatory polymorphonuclear (PMN) cells from human blood samples. We conduct a complex test panel, where we examine the spontaneous migratory behavior of the PMN cells, which reflects one aspect of immune surveillance. In parallel, we also examine altered migratory behavior in response to bacterial presence, versus inflammatory mediators produced by the body itself."
She noted that, at times, products might positively support immune surveillance but also inhibit migration in response to inflammatory mediators. "This may help suggest that a product, when consumed, may support normal immune defense mechanisms, but inhibit parts of an inflammatory cascade," she said. Overall, "The natural products industry must tread wisely; claims must be backed by proper research," she advised.
Herbs & Extracts
Lonza, Allendale, NJ, recently launched ResistAid, an all-natural, multifunctional product that contains the soluble polysaccharide arabinogalactan and bioactive flavonoids derived from larch tress. According to Bryan Rodriguez, technical marketing and scientific affairs manager at Lonza, larch arabinogalactan's mechanisms of action include effects on lactic acid-producing bacteria or bacterial constituents on immune cells, the production of short chain fatty acids (SCFA) and binding to SCFA receptors on leucocytes, but also direct effects on components of the immune system.
Interestingly, Mr. Rodriguez noted, several "immune-enhancing" herbs contain significant amounts of arabinogalactan, such as Echinacea purpurea, Baptisia tinctoria or Thuja occidentalis, and researchers speculate this is one of the main immune-activating principles in these herbs.
For years echinacea has been widely used as a supplement for immune health. "Echinacea has good studies for respiratory tract infections like bronchitis associated with the common cold in children," said Draco's Mr. Quirk. "The public still perceives echinacea to be helpful for the common cold even though the mainstream media has cast doubt with some poorly designed negative studies using lower than normal dosages of unapproved preparations."
Meanwhile, newer ingredients are emerging on the scene. Nick Falk, business development director, Marinova Pty Ltd, a biotechnology company based in Cambridge, Australia, said researchers recently completed a two-arm open label pilot study of the company's Marinova Extract, a fucoidan and polyphenol rich seaweed extract. The study involved five healthy patients, who received 100 mg (clinical dose) or 1000 mg (safety test dose) of Maritech Extract.
The study compared baseline in vivo and ex vivo changes of antioxidant levels and various immune cell functions over a four-week period. In the short-term (three days) the extract caused a spike in immune cell activity, specifically for B Cells (CD19), cytotoxic T cells, monocytes and natural killer cells. In the long-term (daily dose for 28 days) activity levels of monocytes and granulocytes increased significantly.
"There are very few ingredients that have been able to demonstrate both short-term and long-term effectiveness," said Mr. Falk. "It's very strong immune data." Results are expected to be published this year in the peer-reviewed journal Alternative and Complementary Medicine.
Cause & Effect(iveness)
Looking at the broader picture, many experts have acknowledged a rise in prevalence of immune disorders. Gourmet Mushrooms' Mr. Law said the proliferation of novel industrial molecules from pesticides, plastics, food additives and other compounds has contributed to such an increase. "The pro-inflammatory and anti-inflammatory functions of our immune cells are off balance due to constant environmental assaults," he said.
Immune support has been one of the key selling points for mushrooms, according to Mr. Law, and his company emphasizes the use of its products in the modulation of internal cellular communications.
"Mushroom extracts are botanicals with strong consumer awareness for immune health since there is ample research and actual applications in countries like Japan, South Korea and China," said Draco's Mr. Quirk.
Recent research published on Active Hexose Correlated Compound (AHCC), an ingredient derived from the hybridization of several subspecies of medicinal mushrooms, shows it may stimulate the immune system and help the body respond to a broad spectrum of infectious threats. AHCC is manufactured by Amino Up Chemical Company in Sapporo, Japan and distributed in the U.S. by Maypro Industries, which sells AHCC to several leading supplement companies, including Quality of Life Laboratories, a subsidiary of Maypro.
The scientific review analyzed outcomes from in vivo studies and reported that AHCC activates important immune white blood cells, including macrophages, natural killer cells and lymphokine activated killer (LAK) cells following foreign challenges such as influenza virus, avian influenza (bird flu), MRSA, Klebsiella pnuemoniae and Candida albicans. Ongoing research is examining AHCC's ability to impact T cells related to cellular immunity and determining if AHCC supplementation can serve as a beneficial vaccine adjuvant for the flu shot.
In addition to the overuse of antibiotics and rising environmental toxicity, Steve Siegel, Ecuadorian Rainforest, LLC, Belleville, NJ, said poor nutrition and increasingly stressful, on-the-go lifestyles play significant roles in diminishing the immune system's effectiveness. "Individuals wishing to live a healthy lifestyle should incorporate a variety of fruits and vegetables into their daily diet," he said. "Ecuadorian Rainforest supplies a colorful variety of ingredients derived from 'whole food' sources to meet these demands."
The company offers a range of products that contain optimal amounts of vitamin A, which has been shown to fight off infections, according to Mr. Siegel. Ecuadorian also supplies vitamin C-rich foods. "Vitamin C has been shown to support a healthy immune system by assisting the body's natural ability to heal itself," he noted.
Alongside efficacy, safety will continue to be a critical market factor. For example, Canada's number one selling cold and flu remedy, COLD-fX-derived from North American ginseng-from CV Technologies, Edmonton, Alberta, Canada, is currently intended for adults and children 12 years of age and older. But a recent randomized, double-blind, placebo-controlled study published in the journal Pediatrics demonstrated its safety in younger children too. Of 75 children recruited for this trial (ages 3 to 12), 46 developed a URTI and were assigned to receive acute three-day treatments with either placebo or COLD-fX. Both were well tolerated with no significant adverse reactions.
Ironically, these findings come at a time when drug companies that make non-prescription cold and cough medicines say they will stop marketing over-the-counter drugs to children under the age of 4. This pledge recently coincided with an extensive federal review of whether the drugs are safe and effective for children under 12. Americans spend an estimated $300 million on non-prescription children's cold remedies every year.
