Each year in the U.S. alone, at least 2 million people are infected with antibiotic-resistant bacteria, and more than 23,000 die as a result, according to the U.S. Centers for Disease Control and Prevention. In addition, many more people die as a result of complications due to these infections.
In a new guidance for industry issued Dec. 11, 2013, FDA urged food producers to phase out “the use of medically important antimicrobials in animals for food production purposes, such as to enhance growth or improve feed efficiency.” Additionally, FDA plans to phase in veterinary oversight for the use of these drugs in animals for therapeutic uses only.
This change comes in part due to concerns of overuse of antibiotic drugs leading to antimicrobial-resistant bacteria. The agency requested pharmaceutical companies respond in the next three months with their plans to sign on to the revisions voluntarily, and then the companies will have a three-year transition period to comply with FDA’s recommendations.
In the meantime, consumers are looking for ways to protect themselves from illness in the first place. According to a 2012 study published in the Journal of the American Medical Association, immune health was one of the top three reasons consumers took supplements in the past two years, above concerns including “pain relief,” “weight control” or “reducing heart attacks,” said Richard Mueller, CEO of Biothera, Eagan, MN.
Keeping the Lead
While seasonal cold and flu challenges remain an immediate concern for many dietary supplement consumers, suppliers stressed the “best offense is a strong defense” message to promote their immune support ingredients.
InterHealth Nutraceuticals, Benicia, CA, promotes its Aller-7 proprietary blend of seven herbal extracts for daily immune and respiratory health. In concert with a balanced diet, “Aller-7 promotes respiratory health and normal breathing seasonally and all year round,” said Paul Dijkstra, CEO, InterHealth.
Aller-7 contains an Ayurvedic-inspired blend of: Indian gooseberry, or amla, (Phyllanthus emblica); haritaki (Terminalia chebula); bedda nut tree/bahera (Terminalia bellerica); Indian walnut bark (Albizia lebbeck); ginger root (Zingiber officinale); Indian long pepper (Piper longum); and black pepper (Piper nigrum).
“Consumers are really taking their health seriously, wanting to manage their immune and respiratory health on a year-round basis, not just in the moment,” said Mr. Dijkstra. “Ingredients such as Aller-7 that have been shown to be beneficial for immune and respiratory health may grow in popularity for consumers looking for a lifestyle change and to address their health management directly.”
Strong clinical support for nutritional ingredients continues to play a leading role in nutraceutical manufacturers’ formulation strategies. Companies invest heavily in research to demonstrate product efficacy as well as safety in order to make supported claims and to win consumer confidence.
The immune category’s rapid increase “parallels new research, which uncovers more and more effects of the immune system on the body, and therefore new markets for supplements,” said Bryan Rodriguez, global product manager, Lonza, Basel, Switzerland.
Lonza recently announced the results of a study on ResistAid, its proprietary arabinogalactan extract from the larch tree, published in the October 2013 Journal of the American College of Nutrition. The trial included 75 healthy adults who received either 1.5- or 4.5-gram doses of ResistAid or placebo for 60 days; midway through the treatment period, subjects received tetanus and influenza vaccines and their serum antigenic responses were measured at day 45 and day 60 of the study. The results showed ResistAid’s ability to increase the antibody response to the tetanus vaccine even in adults taking the lower dose, paving the way for “new potential avenues for formulation, as less of the ingredient is required to elicit an immune response,” said Mr. Rodriguez.
Horphag Research, Geneva, Switzerland, also announced new research that supports the immune health claims for its Pycnogenol supplement. The study showed Horphag’s antioxidant plant extract from French maritime pine tree bark combined with well-established immune support nutrients vitamin C and zinc to be effective in shortening the duration of the common cold as well as lessening the seven “pillar” symptoms: runny nose, nasal obstruction, sore throat, sneezing, high temperature, cough and general discomfort.
“Studies show that Pycnogenol can scavenge both hydroxyl radicals and superoxide anions, extend the lifetime and increase the antioxidant function of the ascorbate radical and increase the activity of other internal antioxidant systems, namely superoxide dismutase, glutathione peroxidase and catalase,” said Carolina Burki, director of product development, Horphag Research.
A growing segment of the immune nutritionals market includes products made from yeast. Biothera manufactures Wellmune WGP, a natural beta 1,3/1,6 glucan derived from a proprietary strain of yeast shown in nine human studies—eight of which are published in peer-reviewed journals to date—to “boost key immune cells that help keep the body healthy, without over-stimulating the immune system,” the company’s Mr. Mueller explained.
After consumption, the Wellmune yeast ingredient works through the gastrointestinal tract where it is transported to immune organs throughout the body. “While in the immune organs, immune cells called macrophages digest Wellmune into small fragments and slowly release them over a number of days. The fragments bind to neutrophils via complement receptor 3 (CR3), which are the most abundant immune cells in the body. In fact, neutrophils account for 40-60% of all immune cells. Wellmune primes and strengthens the key immune function of neutrophils that now more quickly move throughout the body,” Mr. Mueller said.
The beta-glucan ingredient has been tested in double-blinded, placebo-controlled studies involving marathoners, medical students and other individuals with active lifestyles, which found that Wellmune reduces incidence of upper respiratory tract infection symptoms and improves a sense of well-being. Wellmune’s most recently published study involved more than 180 men and women and compared beta-glucan supplementation with placebo for the incidence of upper respiratory tract infection (URTI) for 28 days after completing a marathon. Participants reported a statistically significant 37% reduction in the number of cold and flu symptoms.
Another popular beta-glucan formulation backed by strong science is Embria Health Sciences’ EpiCor, a proprietary fermented baker’s yeast ingredient. Previously published studies demonstrated EpiCor’s positive effects on increasing secretory immunoglobulin A (sIgA), an antibody produced in the body’s mucosal linings that plays a major role in the body’s defense against invading pathogens.
In addition to promoting sIgA, another 2008 study published in the online, peer-reviewed Open Nutrition Journal showed EpiCor’s ability to balance the immune system by reducing immunoglobulin E (IgE), another type of antibody responsible for triggering allergic responses and other unhelpful-when-overactive immune system reactions. In this study, 25 healthy adults took 500 mg of EpiCor or placebo for five weeks. At the trial’s end, participants in the EpiCor group showed increased sIgA levels and decreased IgE relative to the placebo, suggesting immune balancing effects. Participants taking EpiCor also reported fewer health ailments overall, including a reduction in seasonal allergy symptoms.
As antibiotics provide an effective means to kill bacteria, many companies in the nutraceutical arena are promoting “good” bacteria to support the immune system. In the last several years, pre- and probiotics have taken off as a burgeoning number of studies back their efficacy in supporting gut and immune health. According to a recent report published by Transparency Market Research, worldwide demand of probiotics was worth $27.9 billion in 2011 and is projected to increase to $44.9 billion in 2018, growing at a compound annual growth rate (CAGR) of 6.8% from 2013 to 2018.
Normal intestinal function and colonic integrity are “two points critical to maintaining digestive and immune health,” according to Patrick Luchsinger, nutrition marketing manager of Ingredion Incorporated, Westchester, IL.
Ingredion manufactures NutraFlora soluble prebiotic fibers, called short-chain fructooligosaccharides (scFOS) that are not digested by salivary or digestive enzymes, but instead feed beneficial strains of bacterial, particularly Bifidobacteria and Lactobacilli, species that produce short chain fatty acids (SCFA).
“SCFA promote protective effects on the gut and host, such as increased gut integrity, enhanced immunity through pathogen inhibition, reduction of putrefactive substances, improved normal bowel function and improved nutrient metabolism and absorption,” Mr. Luchsinger explained.
In addition to prebiotic fibers that feed healthy gut bacteria, probiotic formulae provide consumers with live “good” bacteria to enhance healthy immune function. Taken as a whole, research results on probiotics and immune function appear to be mixed and highly dependent on the strain, formulation and study design. Thus, many companies have been hesitant to make immune health claims, but the answer is for manufacturers to focus on strain-dependent methods of delivery and back their claims with strong science, said Michael Bush, senior vice president, Ganeden Biotech, Mayfield Heights, OH.
One difficulty with probiotics is making sure the beneficial bacteria reach the intended target—the intestinal tract, and “certain strains can’t survive in various states” of the digestive process, Mr. Bush noted. GanedenBC30 (Bacillus coagulans GBI-30, 6086) is a spore-forming bacterium that protects the beneficial material through the manufacturing process and during the trip through the digestive tract.
From the Mouths of Babes
As research continues to support the use of probiotics for gut health and immunity, new strains of beneficial bacteria with other applications continue to be discovered. For example, the mouth is the first step in the digestive process and can provide the first line of defense against illness. Streptococcus salivarius, available commercially as BLIS K12 from Stratum Nutrition, St. Charles, MO, works locally in the oral cavity by producing bacteriocin-like inhibitory substances (BLIS) that crowd out harmful bacteria such as S. pyogenes and promote oral health, resulting in a decreased risk of cavities, reduction of halitosis (bad breath) and immune system support.
A study published in 2012 in the peer-reviewed International Journal of General Medicine involving 82 children showed an impressive reduction in pharyngeal infections (sore throats attributed to “bad” strep and/or tonsillitis) and otitis media episodes (ear infections). Of the 82 study participants, 65 of the children had a recent diagnosis of recurrent strep and 17 did not. Study designers assigned 45 of the recently sick kids to 90 days treatment with a slow-release lozenge-like tablet containing five billion colony-forming units (CFU) of S. salivarius K12, with the remaining 20 children serving as a control group. The 17 healthy kids served as an untreated control group. After the 90-day treatment period, the 41 children who completed the K12 treatment showed a 90% reduction in their recurrent strep infections and a 40% decline in acute otitis media.
Even more impressively, the oral probiotic treatment had persistent protective effects, even after its administration was ceased. During the 6-month follow-up period after taking the K12 oral tablet, subjects reported a 65% reduction in throat and ear infection compared to the previous year. Additionally, the study administrators reported no adverse events for the participants taking BLIS K12 and the high rate of compliance shows a promising delivery method for children who may be adverse to swallowing pills.
Medicinal mushrooms and related proprietary formulae comprise another growing area of the immune nutraceuticals market. With a long history of use in Traditional Chinese Medicine (TCM) and other folk medicine, researchers today are discovering more about fungi’s ability to modulate immune function and applications for human health.
Popular mushroom varieties leveraged for their immune health benefits include reishi (Ganoderma lucidum), shiitake (Lentinula edodes), maitake (Grifola frondosa), and turkey tail (Coriolus or Trametes versicolor).
Mushroom mycelial biomass, and specifically metabolites present in mushroom mycelium, “contain much information on defense that could benefit us,” said David Law, president and CEO, Gourmet Mushrooms, Inc., Sebastopol, CA.
“Since the fungal DNA is close to mammalian DNA, much of the information from the fungal metabolites may support our immune functions by aiding intercellular signaling,” explained Mr. Law.
Therapeutic mushrooms contain beta-glucans, like the previously mentioned nutritional yeast ingredients, in addition to other active compounds such as alpha-glucans, enzymes, prebiotics and antioxidants. These bioactive components serve to modulate cytokine (hormone messengers that produce most of the biological effects in the immune system) activity. One major source of cytokines is T lymphocytes, cells that can recognize specific foreign pathogens while also distinguishing normal tissue during an autoimmune episode.
Specific T lymphocytes, also called helper T cells, produce the majority of the body’s two types of cytokines: Th1 and Th2. While Th1 cytokines produce the proinflammatory response the body needs to fight invading immune challenges and perpetuate autoimmune responses, Th2 cytokines serve an anti-inflammatory purpose that balances the immune system to avoid unnecessary damage. An ideal immune response would provide a balance of the proper Th1 and Th2 cytokines to fight the threat effectively, which is a strong focus of Gourmet Mushrooms’ research.
“The cytokine profiles of our immune system are modified or supported by fungi,” said Mr. Law. The company formulates mushroom blends that include different morphology such as gilled fungus, polypores, jelly fungus and sclerotia that help the TH1/TH2 shift in human immune systems due to infection or circadian effects.
“Each mushroom variety is programmed to deal with pathogens unique in its habitat,” Mr. Law explained. So, for example, antiviral properties are most sought after for cold and flu protection. However, care must be taken not to over-stimulate the immune system to create an adverse effect, he added. Historically, the most devastating influenza pandemics such as the 1918 flu outbreak and the H1N1 viruses of recent years devastated many with strong immune functions.
“The over activity of immune responses of young bodies was the main culprit as the cause of death,” Mr. Law noted. “The very young and the elderly had a higher rate of recovery. We have to be careful to make sure that we do not formulate a product that may increase immune responses in the wrong direction.”
Going forward, Mr. Law predicted increasing attention paid to mushrooms’ health benefits and development of mushroom-containing functional or medicinal food, citing fungi’s prebiotic properties that help support a sound microbiome (balanced gut environment) in the system.
Other manufacturers like NutraGenesis, LLC, Brattleboro, VT, are already capitalizing on mushrooms’ immune health benefits by formulating nutritional ingredients with fungi, at times combined with herbal preparations. NutraGenesis cited MaitakeGold 404 and WellBody365 as its two leading patented immune support formulas.
WellBody365 combines maitake mushroom extract with Sensoril, a multi-patented ashwagandha (Withania somnifera) extract that increases the body’s resistance to stress, according to Felicia Tempesta, marketing coordinator, NutraGenesis. Ashwagandha, often called Indian ginseng, has a well-documented history of use as an adaptogen (a substance used to restore balance in the body and reduce overall stress) in Ayurvedic medicine. The combination of the maitake extract’s immune modulating properties with ashwaganda’s adaptogenic abilities make WellBody365 a multifunctional immune support solution for everybody, according to Ms. Tempesta.
In one study performed at the University of Louisville by renowned immunologist and beta-glucan expert Dr. Vaclav Vetvicka, mice supplemented with WellBody365 showed reduced corticosterone (the mouse equivalent of the cortisol stress hormone in humans) levels and enhanced immune function in stressed and non-stressed conditions compared to mice fed a normal diet that did not include the nutraceutical. In a separate human clinical trial, participants taking Sensoril showed a significant reduction in stress (a 69.9% decrease) and cortisol levels (down by 24.2%).
In addition, ongoing human clinical trials at the Memorial Sloan-Kettering Research Hospital found the dosage of maitake mushroom extract used in WellBody365 “increased lymphocyte activity and cytokine levels for enhanced immune system function,” said Ms. Tempesta. As a result of these trials, the maitake extract received an Investigational New Drug (IND) number, she added.
Evidence Wins Out
While the immune support category for nutraceuticals continues to grow in the face of increasing healthcare costs, environmental challenges and everyday stress, savvy consumers will continue to gravitate toward science-based, effective supplement solutions.
“Dietary supplements containing efficacious nutraceutical ingredients are in increasing demand by consumers who seek natural solutions to help support their health and wellness,” said Bruce Abedon, PhD, director of scientific affairs, NutraGenesis. “By educating consumers to the benefits that all-natural dietary supplements can provide (without side effects common to pharmaceuticals), dietary supplement products can provide increased wellness for a growing portion of the population.”