As we’ve learned throughout this editorial series on immune health, there are many ways we may become vulnerable to illness and many ways we may fortify our bodies against it. Herbs have a long history of use in a variety of cultures, the most notable of which include India’s Ayurvedic system of medicine and Traditional Chinese Medicine (TCM). In July we learned about adaptogenic herbs and how they support the endocrine system to manage stress and improve sleep, which plays an important role in our immune health. This month, to close our series, WholeFoods talked to experts to understand various herbs on the market and their overall role in immune health.

Herbs and the Immune SystemDavid Winston RH (AHG), founder and president, Herbalist & Alchemist, Washington, NJ explains that herbs can function in different ways to stimulate the immune system. “Some herbs stimulate the surface immune system (what in TCM is called the Wei Qi, which from a western perspective would include macrophages, phagocytes, monocytes and neutrophils),” he says. “These herbs are immune stimulants used to deal with acute infectious illness.” Herbs that stimulate the surface immune systems, says Winston, include echinacea, elderberry or flower and andrographis.

Winston also describes two different types of internal (specific) immune response; cell mediated and humoral. “Cell mediated which includes the T lymphocytes (Th1 T lymphocytes, T helper cells, T suppressor cells, T cytotoxic cells and Lymphokines) protects against viruses, fungi, protozoans and intracellular bacteria,” Winston says. “Herbs that promote cell mediated immune response include reishi (Ganoderma), usnea, myrrh, garlic, lomatium and Chinese honeysuckle flower.”

The humoral (immune globulin) mediated response, explains Winston, includes the B lymphocytes as well as the Th2 T lymphocytes and protects against extracellular bacteria, amoebas, some viruses and allergens. “Herbs that stimulate humoral immunity include elderberry, echinacea, basil, thyme,” he says. “Herbs that inhibit excessive TH 2 T lymphocyte activity include turmeric, gotu kola, dan shen, baikal skullcap, bupleurum and boswellia.”

Winston also describes what he calls the immune reservoir, a concept he created based on the idea in TCM of the body’s ability to mount an appropriate response. It helps illustrate where immune response will occur from. “While there is not an actual ‘immune reservoir,’ the bone marrow, gut immune system and intestinal microbiome correlate most closely as an anatomical ‘immune reservoir,’” he explains. “Immune potentiators such as reishi, astragalus, maitake, cordyceps, turkey tail, codonopsis, chaga, and licorice are useful for strengthening overall immune response. Many herbs [such as licorice, ashwagandha, Asian and American ginseng, reishi, maitake, astragalus, cordyceps] that affect the immune reservoir also act as immune amphoterics, which are herbs that normalize immune response whether it is hypoactive, hyperactive or both.”

Synergy and FormatMost if not all of the herbal formulations on your shelves contain multiple herbs. There is good reason for this. “The use of a single herb (simples) is almost unknown throughout the world’s great herbal medical systems,” says Winston. “ Skillfully combining herbs creates synergy (1+1 = 3 or 4 or 5). There is also anti-synergy or antagonism (1+1 =1). So just throwing a bunch of herbs together is not the answer. You need to understand how each herb works, how to use other herbs to enhance absorption, decrease toxicity and affect multiple pathways of activity so there is a multiplicity of actions all encouraging the body toward health.”

Rachel Kilroy, brand manager, Solaray Herbs, Park City, UT, for example, describes how one herb in particular can enhance other herbs in a formula. “Goldenseal, one of the most popular herbs in the U.S., appears to have the ability to increase the efficacy of other herbs,” she explains. “This is why it is often combined with echinacea. Goldenseal contains a golden yellow alkaloid known as berberine, researched for its potential anti-adherent effect on bacteria. In addition, berberine may support increased macrophage activity. Macrophages are immune cells that act as scavengers...detecting, destroying and removing pathogens from the body.”

The way we consume herbs is also important. Liquid forms such as tinctures as well as liquid and dry herbal extracts that can be consumed in capsules or tablets each have something to offer users. As far as tinctures go, absorption is a key benefit. “Tinctures are alcohol and water extracts,” explains Winston. “Alcohol is absorbed sublingually, as well as directly via the gastric mucosa. This means there is no need to digest it as with a capsule or tablet. Alcohol increases absorption by 30% or more.”

Considering the enhanced absorption via mucosal membranes, tinctures or liquid extracts (which are a more concentrated version of the herb) can be taken in smaller doses. “In the case of the bioactive elderberry anthocyanins, a significantly lower dose can yield the same desired immune benefits if dissolved or absorbed within the mouth (i.e., dissolvable tablets, chewables, liquids, etc.) versus encapsulated and swallowed whole,” explains Ryan Reisman, marketing and communications writer, Himalaya Herbal Healthcare, Sugar Land, TX.

Of course, that does not mean dry extracts are inferior, just different. In fact, some herbs are better as a dry extract “Basically, the perception of absorption is closely tied to supplements in liquid form,” says Shaheen Majeed, president, Sabinsa Worldwide, based in East Windsor, NJ. “Major marketing companies know this well when they sell to consumers but it’s not always an inherent property of particular ingredients, especially herbs.”

Because of this perception, some manufacturers might use harsh excipients to force solubility in herbs that aren’t easily soluble, he explains. “For easily soluble herbs a liquid delivery form makes sense, this may give the product an optimal absorption factor vs. delivering it in a regular capsule,” he continues. “However, most capsule formulations can also achieve some great absorption, and its cost will certainly be less and may be more consumer friendly as well.”

In fact, when it comes to extracts, dry and liquid are just different forms of the same thing, says Neil E. Levin, CCN, DANLA, senior nutrition education manager, NOW, Bloomingdale, IL. “Dry herbal extracts are actually the liquid extracts that have been dehydrated or spray dried onto a starch base, so they really would have much the same properties as an extract that is still in the liquid state,” he explains. “Additionally, many dry extracts are standardized, providing additional assurances of quality and efficacy over non-standardized liquids. Absorption and bioavailability typically depend on the form of the extract inside the capsule.”

Other manufacturers are providing the whole herb in dry form rather than extracted. “For us, we’re bringing in the whole herbs and drying them, sterilizing them with a very special process so that we don’t degrade any of the actives or colors or flavor components so that it meets the clean standards for GMP — so it’s not contaminated with lysteria or E. coli — but we then powder it,” explains Randy Kreienbrink, vice president of marketing, BI Nutraceuticals, based in Rancho Dominguez, CA. “So it is a natural powder and our customers buy it as a powder and then they can put them in tablets, capsules and powder mixes or nutritional bars, or rehydrate into liquid-like juices.”

While extracts isolate an active compound of an herb, whole herb formulations, because they reduce the entire herb to a powder, provide the fibrous portions of the herb as well as its naturally-occurring actives.
Skillfully combining herbs creates synergy. There is also anti-synergy or antagonism.

— David Winston, RH, Herbalist & Alchemist
Ultimately, the best form depends on both the type of herb as well as consumer preference. For example, not all liquid extracts are particularly appetizing. “For this reason, liquid softgels and capsules are also available,” says Kilroy. “In my opinion, the best form is always the form that you are most comfortable taking every day.”

Immune FavoritesAndrographis.“Andrographis paniculata also called Kalmegh or ‘King of Bitters’ is traditionally used in Ayurvedic and Chinese medicine,” explains Trisha Sugarek MacDonald, BS, MS, senior director of research & development/national educator, Bluebonnet Nutrition Corp., Sugar Land, TX. “The entire herb possesses various health-supporting activities [but] when isolated in its purest form, it has been shown in the literature and throughout history to possess special pharmacological activities like anti-platelet, anti-hyperglycemic, analgesic, antithrombotic, thrombolytic, antipyretic and antibacterial properties.”

Indeed, randomized placebo-controlled trials have found andrographis to be both effective for reducing the incidence of the common cold as well as acute relief. One study of 109 healthy students administered either placebo or 25 mg of andrographis (specifically ParActic by HP Ingredients, based in Brandenton, FL) found that for the first month, no significant difference existed between groups but during the second and third month, only 30% of those taking the herb had incidence of the common cold compared to 62% in the placebo group (1). Another trial studied 158 adults already exhibiting cold symptoms. Those given 200 mg of andrographis per day for five days experienced a significant decrease in the intensity of symptoms compared to placebo (1). According to Levin, this kind of activity is due to the herb’s enhancement of T-Cell and Natural Killer Cell activity.

Echinacea.A very popular herbal product, particularly for immune health, echinacea is a perennial herb native to the midwestern region of North America. “Echinacea was one of the basic antimicrobial herbs of the mid 1800s through the early 1900s,” says Sugarek MacDonald. “In the early 1900s echinacea became popular in both Europe and America as an herbal medicine for a variety of applications including the common cold, coughs, flus, infections and wound-healing.”

Research has shown efficacy for the herb in immune health support. In one randomized, double-blind placebo-controlled study, for example, 95 subjects with early symptoms of cold or flu were randomly assigned to drink several cups of echinacea tea every day for five days or placebo (2). After 14 days, participants filled out a self-scoring questionnaire measuring the efficacy, number of days the symptoms lasted, and number of days for change. Results of the questionnaire showed that those drinking tea felt better more quickly than placebo.

There was also a meta-analysis of 14 clinical trials that found echinacea reduced the odds of developing the common cold by 58% as well as the duration of a cold by 1 – 4 days (3). “Echinacea is considered an adaptogen and is utilized to stimulate the body’s natural response in the immune system,” explains Sugarek MacDonald. “It has been shown to inhibit hyaluronidase, an enzyme that when activated destroys the protective fortification between cells and allows pathogens to gain access to the body. The herb stimulates T-cells and activates macrophages that destroy foreign intracellular invaders. Echinacea increases levels of properdin, a naturally-occurring metabolite that increases cellular resistance to infection.”

The most notable species used in supplement products areEchinacea purpureaandE. angustifolia, attributing to the great variety of echinacea products on the market, but also the variation in efficacy across products. “The great variety of products — and the fact that the strength of active compounds can vary based on part of plant used, environmental factors, and processing variations — makes it difficult to legitimately compare and combine studies in reviews and meta-analyses,” says Levin. This does not mean you should be less confident about selling echinacea, just that some varieties are more effective and have more consistent results.Echinacea purpureais considered by many to be the ideal form. For example, in GermanyEchinacea purpurea, particularly the above-ground portion of the plant, is approved to treat colds, upper respiratory tract infections, urinary tract infections, and slow-healing wounds (4). However, the root of another species, calledEchinacea pallidais approved for the treatment of flu-like infections.

Elderberry.According to Sugarek MacDonald, Elderberries (Sambucus nigra) are members of the Caprifoliaceae (Honeysuckle) family that are grown predominantly in Europe and parts of the United States. They have a long history of use, like all herbs, utilized by Native Americans who made tea from the elderberry flower to help support respiratory issues. “Elderberry provides vitamins A and C, as well as anthocyanins, which are potent free radical scavengers,” says Levin. While both the berries and flowers can be used, the berry, according to the University of Maryland Medical Center, outranks the likes of blueberries, cranberries, goji berries, and blackberries in total flavonol content, which has antioxidant properties that may help prevent damage to the body’s cells (5).

“By donating electrons to free radicals, they can neutralize them thus preventing oxidative damage to cells, tissue and organs,” says Sugarek MacDonald, explaining the function of free radicals. She adds, “Additionally, elderberry constituents neutralize the activity of hemagglutinin spikes (i.e., the increase of a substance that causes red blood cells to agglutinate) found on the surface of several viruses. These spikes, when deactivated, inhibit certain viruses from piercing cell walls or entering cells to replicate, thus resulting in reduced infectivity of certain pathogens.”

Myers agrees, citing anthocyanins, quercetin and rutin as the compounds that interfere with viruses. “Plus, they activate the body’s own antiviral ‘police force’ of phagocytes to move toward any cells that are under attack,” she adds.

Indeed, the herb’s potential antibacterial and antiviral activities were demonstrated in a study of liquid cultures using an extract at concentrations of 5%, 10%, 15% and 20% (6). At 10%, the extract decreased the growth of against Gram-positive bacteria of S. pyogenes, group C and G Streptococci, and the Gram-negative bacterium B. catarrhalis by 70%. Against viral pathogens, MDCK cells infected with the IV strains B/Massachusetts/71 (B/Mass) and A/Thailand/KAN-1/2004 (KAN-1, H5N1) were incubated for 48 hours in the presence of elderberry extract, which was found to produce “a clear reduction of foci size for B/Mass compared to the untreated control,” meaning that it reduced the spread of the virus within the cell culture.
Your immune system isn’t a magic switch you can simply flip on with the right supplement. — Ryan Reisman, Himalaya Herbal Healthcare
A very recent and now oft-cited randomized, double-blind, placebo-controlled study on elderberry supplementation was published in Nutrition in 2016 (7). The study involved 312 economy class passengers travelling overseas from Australia on a seven-hour minimum flight, less than 12-hour stopover and a minimum of four days spent at the destination. Participants took either placebo of a capsule of elderberry extract twice a day for 10 days prior to travel, then three capsules per day one day prior to departure until five days after arriving at their destination. Subjects were evaluated at baseline (–10 days), before travel (–2 days) and after travel (+4/5 days), as well as recording cold symptoms in a daily diary. Results showed that while the extract did not significantly reduce the occurrence of illness during travel (though fewer subjects in the experimental group did fall ill), the duration and severity of symptoms was significantly smaller in the experimental group. On average, those taking the elderberry extract that did get sick were sick for two days fewer than the placebo group.

“This randomized, double-blind placebo-controlled clinical trial provided strong evidence for the efficacy of an elderberry extract produced through a unique process called Holistic Membrane Extraction,” says Melanie Bush, director of science and QC communications, Artemis International, based in Ft. Wayne, IN. This is a proprietary solvent-free process of extraction that delivers a whole-fruit matrix with the necessary phytonutrients to support immune health.

Astragalus.Used in TCM for thousands of years, astragalus is an adaptogenic herb with anti bacterial and anti-inflammatory properties. Recent Chinese research also suggests that it may be an antioxidant as well (8). “Astragalus membranaceus and its root, Radix astragali, were and are still to this day, commonly used for medicinal purposes,” explains Sugarek MacDonald. “Its Chinese name, Huang Qi, means ‘yellow leader,’ which is fitting considering the plant’s natural golden color and its stature for use in Traditional Chinese and Japanese Kampo Medicine.”

“A flurry of new research confirms this herb’s immune stimulating properties and suggests that it may also ease infection-related inflammation. Astragalus directly stimulates macrophage activity, promotes dendritic cell maturation, and significantly reduces interleukin-6 production,” says Jay Levy, director of sales, Wakunaga of America Co., Ltd., Mission Viejo, CA. “Interleukin-6 (IL-6) is a substance produced by T-cells and macrophages that acts as either a pro-inflammatory or anti-inflammatory agent according to the body’s needs.”

As an adaptogen, astragalus is also ideal for long term maintenance. “Unlike many other herbs that support the immune system, astragalus can be taken on a daily basis,” says Kilroy. For example, Levin describes an adaptogen formula (NOW Immune Renew) that combines astragalus with a high beta-glucan proprietary mushroom blend consisting of an organic mycelium biomass, which he says can be used daily throughout the year.

Mushrooms.When it comes to immune health, mushrooms are gaining momentum in the market, says Olagne, citing cordyceps and chaga as two types that are popular. Part of their appeal is that most mushrooms are rich in beta-glucans. We discussed beta-glucans in a proprietary baker’s yeast earlier in our immune health series framed around the topic of digestive health and the immune system (9). “Beta-glucans are believed to act as prebiotics, nourishing certain probiotics such as Bifidobacteria,” says Levin.

“Glucan receptors have been identified on various immune cells,” adds Kilroy. “Immune cells ingest the beta-glucan, which nourishes them and makes them stronger.”

Mushrooms commonly found in immune formulas include maitake, reishi and shiitake. These fungi, says Levy, are rich in a variety of compounds including beta-glucan, lentinan — which helps fight infection — and active hexose correlated compound (AHCC), an immuno-modulating compound which he says increases the body’s antibody response to the flu vaccine, improving its effectiveness.
Absorption and bioavailability typically depend on the

form of the extract inside the capsule.

— Neil E. Levin, CCN, DANLA, NOW
Kilroy explains that reishi is particularly packed with plant compounds that include glycoproteins, triterpenoids and ergosterols. “All of these compounds are pre-cursors to beta-glucans — polysaccharide fibers that stimulate and feed white blood cells,” she says. “We all know how important white blood cells are to our immune system!”

Olive Leaf.The first botanical mentioned in the Bible, says Majeed, olive leaves have been used medicinally for a very long time and modern science now attributes this to the compound oleuropein. The leaves of the trees themselves are known to be resistant to insect and microbial attacks, explains Sugarek MacDonald and have therefore been extensively studied scientifically for their antimicrobial activities.

In vitro and in animal studies, oleuropein has been shown to be effective against numerous microorganisms, such as retroviruses, coxsackie viruses, influenza, parainfluenza and some bacteria (10). “Research suggests that olive leaf constituents interact with the protein of virus particles and reduce the infectivity and inhibit replication of viruses,” explain the authors of an article detailing botanical remedies to cold and flu (10).

Oregano.Certainly an herb you are familiar with, oil of oregano is known as a powerful antibacterial and antimicrobial agent. “The most potent and perfect blend of active compounds in oregano are carvacrol and thymol, and because of this, have been the focus of most of the research on this herb,” says Myers. Kilroy agrees, though she adds that research into its ability to support the immune system has shown that higher carvacrol content in the oil achieves better results.

Garlic.“Allicin, one of the immune-stimulating nutrients in garlic, is released when you cut, chop or crush the cloves,” explains Sugarek MacDonald. “This active constituent not only stimulates our body’s own immune response by activating immune cells like macrophages and killer T-cells that go after foreign invaders, it also acts as a potent antifungal/ antimicrobial/anti bacterial by getting rid of foreign invaders itself.” In vitro studies, she adds, show garlic’s ability to fight Gram-negative and Gram-positive bacteria species such as:Escherichia, Salmonella, Staphylococcus, Streptococcus, Klebsiella, Proteus, Bacillus, ClostridiumandMycobacterium tuberculosis.

Garlic supplements are processed in various ways, depending on the company. One of the foremost manufacturers of garlic supplements is Wakunaga of America Co., Ltd., which ages the garlic in carefully controlled conditions for 20 months. According to the firm, this converts harsh and unstable organosulfur compounds into mild and effective ones such as allicin and sulfides.

Levy cites a randomized, placebo-controlled trial conducted by the University of Florida, which studied the company’s aged garlic extract (AGE) on healthy adults between 21 and 50 years of age over 90 days during cold and flu season (11). While those assigned AGE did not demonstrate a significant reduction in the occurrence of sickness, there was a significant reduction in the severity of symptoms and length of illness. “According to the researchers, this was because AGE boosted the number of T-cells, especially natural killer (NK) cells,” explains Levy. “Earlier research found that taking supplemental AGE for six months significantly increased the number and activity of NK cells in patients with advanced cancers (liver, pancreatic, and colon).”

Another type of garlic supplement is fermented black garlic, whose active compound is called S-Allycysteine. “The fermentation process really changes the whole composition of the garlic,” explains Nitesh Khakhar, sales manager, HealthAid America, Sunnyvale, CA. “It makes it so much more potent, it has a greater nutrients and antioxidant profile.”

Bigger PictureAs we close our editorial series on immune health, it’s important to reflect on what we’ve learned. While there are so many wonderful products on the market, our immune health cannot be sustained on supplements alone. It’s important to educate customers who seek immune support that they should develop a regimen that includes eating well, physical activity and dietary supplements for extra support.

“Your immune system isn’t a magic switch you can simply flip on with the right supplement,” says Reisman. “Your body has a very symbiotic relationship with the pathogens that challenge your immunity.”

You likely see it often, the sniffling patron seeking symptom relief or a “cure” that doesn’t exist. Getting sick is easy. “An ounce of prevention is worth a pound of cure… you’ve heard it a million times, but how does it practically relate to illness prevention?” posits Sugarek MacDonald. “Following a lifestyle that is intended for wellness will go a long way toward preventing illness, as you will be supporting the body to function at an optimal level.” The immune system is a profoundly diverse and fascinating force in our bodies and we should treat it with respect because it is only as good as we are to ourselves.WF

References
  1. “Paractin: Scientific Breakthrough for Bone, Joint and Muscle Health.” WholeFoods Magazine. https://wholefoodsmagazine.com/multimedia/ebooks/paractin-scientific-breakthroughs/ 2016.
  2. G.F. Lindenmuth and E.B. Lindenmuth. “The Efficacy of Echinacea Compound Herbal Tea Preparation on the Severity and Duration of Upper Respiratory and Flu Symptoms: A Randomized, Double-Blind Placebo-Controlled Study.” The Journal of Alternative and Complementary Medicine. 6(4): 327-334. 2004. https://doi.org/10.1089/10755530050120691
  3. S.A. Shah, et al. “Evaluation of echinacea for the prevention and treatment of the common cold: a meta-analysis.” The Lancet. 7(7): 473-480. 2007.
  4. “Echinacea.” University of Maryland Medical Center. http://www.umm.edu/health/medical/altmed/herb/echinacea, Accessed July 20, 2017.
  5. “Elderberry.” University of Maryland Medical Center. http://www.umm.edu/health/medical/altmed/herb/elderberry, Accessed July 20, 2017.
  6. C. Kravitz, et al. “Inhibitory activity of a standardized elderberry liquid extract against clinically-relevant human respiratory bacterial pathogens and influenza A and B viruses.” BMC Complement Altern Med. 11(16). 2007. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3056848/, Accessed July 20, 2017.
  7. E. Tiralongo, et al. “Elderberry Supplementation Reduces Cold Duration and Symptoms in Air-Travellers: A Randomized, Double-Blind Placebo-Controlled Clinical Trial .” Nutrients. 8(4), 182. 2016. http://www.mdpi.com/2072-6643/8/4/182/htm, Accessed July 20, 2017.
  8. “Astralagus.” University of Maryland Medical Center. http://www.umm.edu/health/medical/altmed/herb/astragalus, Accessed July 20, 2017.
  9. S. Krawiec. “Follow Your Gut to Better Immune Health.” WholeFoods Magazine. https://wholefoodsmagazine.com/supplements/features-supplements/follow-your-gut-to-better-immune-health/ 40(6): 43. 2017.
  10. M. Rokas and J. Jurenka. “Colds and Influenza: A Review of Diagnosis and Conventional, Botanical, and Nutritional Considerations.” Alternative Medicine Review. 12(1). 2007. http://www.altmedrev.com/publications/12/1/25.pdf, Accessed July 20, 2017.
  11. S.S. Percival. “Aged Garlic Extract Modifies Human Immunity.” The Journal of Nutrition. 146(2): 433S-436S. 2016. http://jn.nutrition.org/content/146/2/433S.long, Accessed July 20, 2017.
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Published in WholeFoods Magazine September 2017