Can we program or stimulate the immune system to perform better? If we could, it would solve many of the problems caused by viruses, other infections, and cancer. Unfortunately, though we can condition the immune system, stimulating it is not like training a watchdog. It is much more complex: There is no simple “on” or “off” button.
To protect us and keep us alive, our immunity adapts to constantly changing environmental influences and evolves in a manner based upon principles we are only just beginning to understand. Though we cannot yet program the immune system, there are ways to manage and enhance its functions. This chapter will discuss natural immune modulators and how to use them, including information on clinical advances that might in time help us enhance immunity against the modern viral plagues.
Immune modulators (immunomodulators) are substances that have regulating effects on the immune system. Researchers often use the term biological response modifiers interchangeably with immunomodulators. To allopathic medicine, immunomodulators include a variety of drugs that either down-regulate (suppress) or up regulate (increase) immune activity. These include steroids, interferon, and inosine, a substance that increases the effect of interferon and which has been studied in the treatment of herpes simplex virus.
From the alternative medicine perspective, natural immune modulators are thought to tune up the immune system and to reverse or prevent illnesses related to immunity, aging, and chronic infection.
Immune modulators have also been called immunostimulatants, immunoceuticals, and immunotics. This is a term with a familiar ring to its suffix in that it refers to pharmacologically produced substances like pharmaceutics (drugs) and nutraceutics (pharmacologically manufactured nutritional or herbal substances in more concentrated amounts than occur naturally). Immunotics, a term coined by Robert Rountree, M.D., is also semantically connected to probiotics (substances like acidophilus that support natural microflora) and antibiotics (medications that destroy bacteria including microflora) (Rountree 2000). Regardless of what term is used, the substances and medications in this chapter are immune-enhancing—stimulating—and boosting agents.
What Do Immune Modulators Boost? Until the 1990s, most of the research on natural immune-enhancing agents has focused on the treatment of cancer. From the results of this research, many of these agents were found to affect the immune system in a manner that also improved antiviral activity. The majority of the early research in the viral area was for the treatment of AIDS, later for herpes viruses and HBV, and now HCV. However, some of the knowledge gained from cancer and AIDS investigations can be applied to other viruses.
We know that immunomodulators increase NK cell activity, enhance B-cell and T-cell function, increase production of various cytokines, reduce pro-inflammatory cytokines, and promote macrophage activity. For the most part, they benefit all aspects of innate immunity. Some are also powerful antioxidants that scavenge cellular debris left by radiation and infection.
Keep in mind that though there are thousands of scientific studies on immune-modulating agents, and that a significant amount of clinical evidence indicates they improve immune activity, they are not sufficiently powerful to work alone in improving immune function. However, a synergy occurs when they are combined with other immune-enhancing agents, such as antioxidants, stress reduction techniques, and phytonutrients. Follow the entire viral immunity program in order to achieve the most benefits along these lines.
Who Needs an Immune Boost? This is easy to answer: in our postindustrial toxic world, everyone needs immune-enhancing. Those with chronic fatigue, all forms of chronic microbial infections including viruses, recurrent colds and flu, cancer, or allergies and asthma, all require immune modulation and most will benefit from these substances. Certain precautions may apply, so read about each immune modulator before you choose which one is best for your condition.
In our postindustrial toxic world, everyone needs immune-enhancing. Those with chronic fatigue, all forms of chronic microbial infections including viruses, recurrent colds and flu, cancer, or allergies and asthma, all require immune modulation and most will benefit from these substances.
From my clinical experience, all my patients with cancer, chronic fatigue syndrome, autoimmune disorders, recurrent infections, and chronic infections (including viral disease) have a disrupted immune system and benefit from immune enhancement. Additionally, immunological concerns are not only involved in diseased states, but are important to everyone exposed to the modern toxic environment—particularly urban dwellers. Given the number of factors that can disrupt the immune system, medicines that have the power to normalize it have enormous potential. To meet this need, many new immune-enhancing medications have been produced from naturally occurring substances, most of them previously used in traditional medicine.
In my clinical opinion, immune dysfunction is becoming increasingly common and may become one of our most serious health concerns. To meet this challenge, evaluating immune status should be a standard part of a regular physical examination. Currently only a complete blood count (CBC) is routinely taken, and only if significant deviations from normal are seen does a medical doctor even take notice. However, with the increasing incidence of immune system disorders and chronic infectious illnesses, as well as cancer, white blood cells should be looked at more closely.
If imbalances are present, or if the patient has symptoms indicating immune dysfunction (such as chronic fatigue or recurrent respiratory tract infections), then a comprehensive T-lymphocyte panel should be performed. By tracking abnormal immune cell levels or activity, such as is done with NK cells, you can judge the effectiveness of your immune enhancement regimen.
The following immune-modulating substances are those that have the best substantiating research behind them and a history of wide clinical use. However, no one knows exactly how they work in the body or the best way to take them to obtain the maximum results. Some companies have put several immune modulators together in one product, as there is some evidence that a synergistic affect occurs. They are all generally safe and there are no known contraindications for mixing them, except where noted.
Acemannan: Indigenous to Africa, but now found globally, there are over 200 known species of aloe. The best known is true or common aloe (Aloe vera, Aloe barbadensis). The raw gel has been used since the time of the Egyptians for the treatment of burns and cuts, and in India for intestinal infections and constipation. It is also considered to have anti-inflammatory properties.
Acemannan, an immune-enhancing mucopolysaccharide (a carbohydrate), is an extracted component found in the gel of the aloe vera leaf. Research has shown it to increase cytotoxic T-cell activity, stimulate macrophage function, and to release interleukin-1 from monocytes. Two prescription drugs have been developed from acemannan by Carrington Labs. Carrisyn, used as an immune stimulating adjunct with antiretroviral therapy in AIDS, has been shown to improve CD-4 counts. Carravet, a veterinary preparation, is used for the treatment of feline leukemia virus and fibrosarcoma (a connective tissue cancer of the bone or around muscles or nerves).
Manapol, also manufactured by Carrington, is a nonprescription oral acemannan concentrate that is used as an immune enhancer. A dose of 40 mg of Manapol is equivalent to 1 ounce of the fresh aloe gel and is taken by mouth in dosages from 80–240 mg daily. Aloe gel, if taken in high dosages, can cause loss of potassium due to diarrhea, but Manapol is considered safe to take in the recommended dosages and apparently does not have the laxative effect of the gel or dried pure concentrate. There are no known drug interactions with acemannan. It is a general immune system booster and is frequently found in combination formulas containing glucans and transfer factor, or with antioxidant vitamins and minerals.
Arabinogalactan: Another polysaccharide, arabinogalactan, is commonly found in nature in carrots, radishes, pears, black beans, corn, wheat, red wine, tomatoes, and coconuts. Several herbs already mentioned in this book also contain arabinogalactans, such as Echinacea purpurea, Baptista tinctoria, and Curcuma longa. The wood of the Western larch tree (Larix occidentalis), native to the Pacific Northwest, provides the raw material for the extraction of medicinal arabinogalactan.
Pharmaceutical-grade larch arabinogalactan is a fine, dry, white powder that readily dissolves in water; it has a slightly sweet taste due to the presence of two sugar molecules: galactose and arabinose. It is considered extremely safe and may even be given to children. There are no known side effects in the recommended dosages other than occasional intestinal gas and bloating due to fermentation by gut flora, and there are no known drug interactions.
Like acemannan, arabinogalactan has been primarily studied as a possible adjunctive anticancer agent. In laboratory studies it was shown to stimulate NK cell and macrophage activity. Larch arabinogalactan can be used as an immune modulator in acute and chronic viral diseases, chronic fatigue, and multiple sclerosis. Peter D'Adamo, N.D., naturopath and the author of Eat Right 4 Your Type, suggests that arabinogalactan acts synergistically with vitamin C (D'Adamo 1996). This combination makes sense because vitamin C appears to enhance the immune-stimulating function of polysaccharides by making them easier to absorb.
The dosage is 1–3 tablespoons (1 tablespoon equals 4–5 g) of the powder per day, mixed in juice or water, and buffered vitamin C may be added. Since it is a good source of fiber and exerts vigorous activity on intestinal flora, the “friendly” bacteria Bifidobacterium bifidum and Lactobacillus acidophilus may be mixed with larch arabinogalactan powder. In one study, these probiotic substances together caused an increase in B cells. For children, the dose of larch arabinogalactan is 1 teaspoon in juice, given in divided dosages 2–3 times per day.
Beta 1, 3-D Glucan: Beta-glucans are components of fungal cell walls and are commercially derived from mushroom species and common baker's yeast. Glucans and proteoglycans isolated from mushrooms also have promising immunoceutical potential. Extracts of cordyceps, a glucan-containing Chinese medicinal fungus, are one of the best of the immune-modulating substances for viral infections. Beta-glucans have been widely studied as biological response modifiers since the 1940s. They have considerable broad spectrum immune-enhancing effects, including tumor rejection, prevention of bacterial infection in postoperative cases, modification functions against certain fungal and parasitic infections, improved immunity in older people, and the treatment of viral diseases.
Beta 1, 3-D Glucan is a pure isolated polysaccharide compound extracted from the cell walls of baker's yeast (Saccharomyces cerevisiae). Like many of the other immune modulators discussed in this section, it stimulates innate immunity and is a powerful antioxidant. Its main activity is as a potent macrophage stimulant; its maximum peak of macrophage activity occurs 72 hours after ingestion. It is prepared as an intramuscular or intravenous medication, and can also be taken orally. The oral dosage range is from 100 mg daily for prevention up to 20 g (20,000 mg) during active infection.
It is considered safe and nontoxic; not only does it have no known drug interactions, beta glucan may help antimicrobial drugs work better. Since it is a pure compound, even though it is extracted from yeast, there are no reported allergic reactions among users with yeast or mold sensitivities.
Mushroom Immunoceuticals: A considerable amount of research has been done on more than fifty different mushroom species with potential immune-modulating properties. They have been known for their medicinal benefits in Asia for thousands of years. However, researchers only discovered the active beta-D-glucan component recently.
Of the many mushrooms studied, five chemicals have shown activity against human cancers: lentinan from the shiitake mushroom (Lentinus edodes); active hexose correlated compound (AHCC), also from shiitake; maitake D-fraction from the maitake mushroom (Grifola frondosa); schizophyllan from Schizophyllum commune; and various proteoglycans (PSK and PSP) from Coriolus versicolor.
The ones most commonly available on the American market are the trade combinations AHCC and MGM-3 (discussed below). Other mushroom extract combinations are also available, and research continues on new promising species. Though few have been researched for their effects on viruses, the significant enhancement of innate immune function they create warrants inclusion in an immune system rebuilding program.
MGM-3: Originally developed in Japan and researched by the internationally recognized immunologist Mamdooh Ghoneum, Ph.D., an expert on how the body's immune system fights cancer, MGM-3 is a patented blend of rice-bran hemicellulose B (a carbohydrate) and three different mushroom extracts including shiitake. This compound has been found to dramatically increase NK cell activity. Besides his work with cancer, Dr. Ghoneum, currently chief of research at Charles Drew University of Medicine and Science in Los Angeles, has also tested MGM-3 on HIV-1 and found it inhibits replication of the virus.
The recommended dosage is 3–4 g, three times daily for two weeks as a loading dose, and then 1–2 g, two times daily thereafter. A “loading dose” is a higher amount of a medication in the beginning of therapy in order to saturate the tissues and achieve adequate therapeutic blood levels of the medication. Once saturation levels are reached, a lower dosage is prescribed to maintain them.
AHCC: A cultured substance from hybridyzed mushrooms, AHCC contains hemicellulose, alpha 1, 4-glucan, and other substances. Like MGM-3, it is used extensively in Japan and Korea as a nutritional cancer preventative, and it is undergoing research as an adjunctive cancer medicine. The recommended daily dose is 6 g divided during the day.
Several anecdotal case reports on chronic hepatitis C involving these mushroom products are circulating on the Internet and indicate liver-protective effects and a reduction in viral load. There seem to be no scientific studies or clinical documentation to verify these claims, yet for those with HCV, including these products into your regimen may be of benefit, especially as there are no known side effects or toxicity associated with them.
GANODERMA: Ganoderma lucidum, the Chinese “mushroom of immortality” called ling zhi (in Japan, reishi) has been extensively studied in the laboratory for antiviral activity and is well known for its immune-modulating activity. My teacher of Chinese medicine, the late Dr. York Why Loo,1 kept a specimen of dried wild Chinese ling zhi in a jar for use in his old age. So revered by Chinese doctors is ling zhi that it is frequently pictured on their business cards or displayed in their shop windows as a sign of respect for its importance.
Several Japanese and Chinese studies indicate that the polysac-charide compounds found in ganoderma have antiviral activity against herpes simplex types 1 and 2. In traditional Chinese medicine, ganoderma is used for weakness and deficiency of the entire system and is thought to be a cardiotonic. It is safe to take, without any known contraindications.
CORDYCEPS: Dong chong xia cao (“winter worm, summer plant”) is a highly valued traditional Chinese medicine composed of the entire fungus, Cordyceps sinensis, and the dried body of the larvae of the moth on which it grows. It tonifies both yin and yang, thereby balancing the body, and it has anti-cancer, antimicrobial, sedative, anti-asthmatic, and adrenal gland-improving effects.
It has been studied extensively in China for its medicinal properties, and though once very expensive, commercial production has lowered its price dramatically. The Beijing Institute of Materia Medica of the Chinese Medical Academy in Beijing, China, found that the cultivated type has the same chemical constituents and is as effective as the naturally occurring form. In addition to its uses listed above, the Beijing researchers found cordyceps to have immune-modulating and anti-inflammatory activity.
Cordyceps increases interferon levels, tumor necrosis factor-alpha, and interleukin-1 and 2. It increases helper T cell counts, improves the helper-to-suppressor ratio, and stimulates NK-cell activity. In viral hepatitis it lowers ALT, increases albumin (a water-soluble protein), improves liver function, and reduces enlargement of the spleen and liver. This action reduces pressure on the portal vein, improves subjective symptoms, and dramatically improves stamina.
With these properties, cordyceps appears to be the ideal natural immune modulator for chronic viral disease. The dosage is 6–15 g of the dried herb made into a tea or 500–1,000 mg of the extract, three times daily, taken 10–20 minutes before food. It is safe even in very high dosages.
Caution: In traditional Chinese medicine, cordyceps is considered safe and may be taken over a long period of time. However, it is contraindicated in external conditions, i.e., it should not be used if fever is present, during an active cold or flu, or the acute phases of a reactivated virus.
Immune Products from Mother's Milk: Colostrum, a thin yellowish fluid, is the first pre-milk substance produced by the mammary glands of female mammals during the few days just after giving birth. It is through the colostrum that the mother passively donates her immunity to the newborn child. Not surprisingly, colostrum contains several immune-modulating products including immunoglobulins, lactoferrin, transfer factor, fibronectin, and growth factors.
Three of these are available commercially and are promising components in a viral immunity program: immunoglobulins, lactoferrin, and transfer factor. I have already discussed whey immunoglobulins, and recommended that you include cold-processed whey powder in your general dietary plan, for detoxification, and for general immune enhancement.
COLOSTRUM: Commercially prepared from dairy cattle, whole purified bovine colostrum can be added to the category of a supportive dietary supplement for an aging immune system and general immune deficiency. It is very safe to use and is taken in dosages ranging from 1–4 g daily on an empty stomach.
LACTOFERRIN: Lactoferrin, an abundant protein component of human colostrum, binds to iron. By binding to iron, lactoferrin makes iron less available for use by bacteria and other pathogenic microorganisms, including fungi and viruses, which use iron to promote their own growth. Lactoferrin's ability to regulate iron also influences T-cell, neutrophil, and monocyte proliferation, all essential components of the immune response. Iron-regulating strategies are also essential to normal growth and the control of the advancement of disease processes in the body.
Several studies support the premise that lactoferrin acts as a natural antibiotic and antifungal agent and that it has anti-cancer activity. Though lactoferrin is found in high amounts in human colostrum, its concentration in bovine colostrum is low, so a separate supplement of lactoferrin should be used. Lactoferrin is useful for fungal and bacterial co-infections in those with chronic viral diseases and to manage iron regulation in hepatitis. Dosages range from 250–750 mg, taken before bed, nightly.
TRANSFER FACTOR: Immunological information is passed from the mother to her child in the colostrum through the action of transfer factor. William Hennen, Ph.D., the father of the modern use of oral transfer factor, refers to it as “graduate level training for the immune system” (Hennen 2000). Transfer factor, along with antibodies in the colostrum and breast milk, passively confers some of the mother's cell-mediated immunity to the infant until it acquires its own. Infants have a very responsive innate immune system; they quickly react to foreign substances with high fever, for example.
But since they have not been exposed to environmental antigens, their adaptive immune responses to foreign substances are less reactive, making them highly susceptible to microbial infection. Mortality among infants and children under five years of age used to account for the greatest number of deaths in the pre-industrial era in the United States and Europe, and it continues to be today in the impoverished third world countries.
Originally discovered in the late 1940s, transfer factor has been the subject of intense investigation for its use as an immune stimulant. It is considered an essential component of the immune system. Most of the current transfer factor research has been conducted in Italy by Giancarlo Pizza, M.D., president of the International Transfer Factor Society. Dr. Pizza and his colleagues investigated treatments with HIV patients, chronic fatigue syndrome, prostate and bladder cancers, HHV-6, herpes simplex, and other viral conditions.
So far in this chapter I have discussed non-specific immune modulators that mainly stimulate innate immunity. Transfer factor (TF), to my knowledge, is the only naturally occurring immune modulator that can affect cell-mediated immunity. Steven J. Bock, M.D., says, “Transfer factor probably produces a trigger for T-cell recognition of antigen” (Bock 2000). He has found TF useful in allergic conditions, autoimmune disorders, and chronic viruses. TF also affects innate immunity by enhancing NK cell activity.
There are two types of transfer factor, unspecific and antigen-specific. Dr. Pizza's work is with antigen-specific transfer factor as prepared from extracts from white blood cells. Commercial antigen-specific transfer factor can be prepared in the laboratory and has activity against specific viruses, fungi, and other infectious microorganisms. Chisolm Biological Laboratories in South Carolina produces antigen-specific transfer factor products from the white blood cells of chickens for a variety of diseases, including hepatitis B and C, HHV-6 and other herpes viruses, as well as Candida and other fungal organisms.
Though there is no conclusive evidence that antigen-specific TF is better than unspecific transfer factor, this conclusion makes sense and I have recommended its use in patients with HCV, Lyme disease, and other infections. Antigen-specific transfer factor can be taken orally or by injection and is administered by a medical doctor or naturopathic physician.
Unspecific transfer factor is prepared from bovine colostrum and is available without a prescription or doctor's recommendation. It is taken orally and is considered very safe, even when taken over long periods of time, and it can be taken by elderly patients and infants as well. For viral infections, the recommended dose is three to five 200 mg capsules taken three times daily with water and away from food.
Caution: Though commercial colostrum, transfer factor, and lactoferrin are made from milk, they are highly purified and contain only small amounts of allergic milk proteins (albumin and gamma globulin) and lactose. Even if you are allergic to dairy or are lactose intolerant, you should be able to take these products. However, start very slowly with a fraction of the recommended dosage and gradually increase the dose. Whole colostrum contains more milk allergens than lactoferrin or transfer factor, so if you notice any allergic symptoms, discontinue immediately.
Nutrients and Herbs As Immune Modulators: Many herbs have immune-modulating effects. For viral conditions, the best known and most effective include echinacea and cat's claw. These herbs also have antiviral activity and are discussed in step 7, the chapter on natural antiviral medications. Many Chinese herbs have immune-enhancing and adaptogenic properties, such as astragalus and ginseng, and are included in step 8, the chapter on Chinese medicine.
Many nutrients also have immune-modulating effects, such as co-enzyme Q10, selenium, zinc, and vitamin B6, and have already been discussed in the chapter on antioxidants. However, one vitamin, folic acid, and a trace mineral, germanium, that I have not discussed, are worth mentioning here for their immune-enhancing properties.
FOLIC ACID: Folic acid, or folate, is necessary for DNA synthesis. It keeps homocysteine levels within normal range, and is used to make SAMe (S-adenosyl-L-methionine). The RDA for folic acid is 200 mcg daily and 800 mcg daily during pregnancy to prevent neural tube defects in the developing fetus. A foundational multivitamin formula and a diet rich in green leafy vegetables, mixed vegetable juices, and green drinks generally supply adequate folate. However, in cases of chronic viral infection, take 1–5 mg daily (1 mg = 1,000 mcg).
GERMANIUM: Germanium is a trace mineral that has been found to improve immunity. The main research was performed in Japan by Kazuhiko Asai, Ph.D., at the Germanium Research Institute in Tokyo; its use as a powerful antioxidant was later promoted by Stephen Levine, Ph.D., an international expert on free radical pathology and founder of Allergy Research Group in Hayward, California. Interestingly, germanium is found in shiitake mushrooms, so I generally prefer to use mushrooms rather than prescribing the mineral itself since it is very expensive. Organic germanium is available from Allergy Research as bis-carboxyethyl germanium sesquioxide; the recommended dosage is 275 mg, three times daily.
CAT'S CLAW: Cat's claw or Uña de Gato (Uncaria tomentosa) has anti-inflammatory properties and has been investigated for immunomodulating activity. Professor Hildebert Wagner of the University of Munich, one of the world's authorities on immune-modulating agents from plants such as echinacea, has found substantial immunomodulating activity in cat's claw.
Though research on cat's claw is still in the preliminary stages, one or two promising products based on it have recently entered the market. For one, C-Med-100 is a patented cat's claw extract standardized to 8 percent carboxyl-alkyl-esters with a recommended dose of 300 mg daily. The other, Saventaro, is an extract of the root standardized to contain 1.3 percent pentacyclic oxindole alkaloids. The recommended dosage is one 20 mg capsule, three times daily as a loading dose for the first ten days, then one capsule daily.
In general, those with any chronic illness or impaired immunity may benefit from immune modulators. One or more of the substances discussed in this chapter may be added to your daily supplement regimen and can be taken often with other vitamins or antioxidants, though they are best taken apart from food. Do not take all of them at one time. Experimenting on your own using immune-modulating medications is safe, but if you have a serious condition, you may find it better to consult a doctor who has experience in immunological disorders and the use of immune modulators.
In my clinical practice, I order a comprehensive lymphocyte panel that includes NK-cell counts and activity for all patients with chronic infections and any immunologically related disorder. I evaluate the number and activity of natural killer cells and the balance between helper and suppressor T cells. I then establish a regimen of immune modulators, along with other natural medications. Besides following improvement in symptoms, it is a good idea to have your NK-cell activity checked every three to six months until it returns to normal, then once a year thereafter until you are completely recovered.