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Aging and Immunity
(16 Immunity Enhancers At A Glance)We live in a world of entropy.

Entropy is the tendency of complex structures to gradually decay or break down with time. Entropy is one of the brute facts of existence. It is codified as one of the basic laws of physics: the second law of thermodynamics, which governs both living and inanimate matter. We humans normally call the process of entropy aging. The anti-aging movement is literally an anti-entropy movement. Modern science has discovered that we can at least slow down entropy through various means such as exercise, proper diet, nutrient supplements and anti-aging drugs.

Unfortunately for us, there is a whole micro-universe of agents of entropy who are literally out to get us - to accelerate our entropic decay. We call them germs and cancer cells. A host of viruses, bacteria, fungi, parasites, worms and cancer cells are ready to invade our bodily turf and wreak havoc with our cells, tissues and organs, leading to disease or even the ultimate entropy - death.

Fortunately for us, we are endowed with a superb, multifaceted, synergistically interacting defense force - our immune system. This amazing defense force can, in principle, defeat any entropic germ science has yet discovered. There is virtually no germ known to be 100% lethal. Even the dreaded Ebola fever virus is usually only lethal to 70-90% of those it infects, before their immune system saves the unlucky 10-30%.

Unfortunately, there are many minor and some major forces of entropy that can weaken, even destroy our immune system's ability to successfully defend us.

One of the most common entropic immune weakeners is malnutrition: malnutrition is the commonest cause of immunodeficiency worldwide, and Nutritional deficiencies are seen in at least one-third of the elderly in industrialized countries. Overeating and obesity, now epidemic in the Western world, also decrease immune function. Stress is also a major assault on immune health. Indeed, the stress hormones cortisol/corticosterone are sometimes used in experiments to weaken the immune system. Perhaps the most inevitable entropic weakener of our immune vigor is aging itself. aging is known to bring about adverse changes in almost every aspect of our immune power. Aging is associated with a decline in immune function that leads to an increased incidence of infection, cancer, and autoimmune disease. Age-related changes in immunity primarily involve alterations in T cell function.

A program consisting of various vitamins, minerals, hormones and anti-aging supplements will cover virtually all the areas - nutritional, stress and aging - that are known to weaken the immune system. Experimental results from in-vitro (test tube), animal and human studies have shown an amazing ability of these anti-entropic biochemicals to repair immune damage, often restoring the measured immune parameter to youthful, healthy levels.

Immunology 101

Immunity may be defined as resistance to our protection from disease. There are two primary divisions of our immune function: innate immunity and acquired immunity.

Innate immunity results from general processes, rather than processes directed at specific disease organisms.

Human natural immunity makes us resistant to such diseases as animal paralytic viral infections, hog cholera, cattle plague and canine distemper.

Acquired immunity results from the response of T cells and B cells (T-and B-lymphocytes) to specific invaders: viruses, bacteria, toxins, animal hair, etc. T and B lymphocytes are both activated by foreign antigens. Antigens are proteins or large polysaccharide molecules that help immune cells recognize self and other - i.e. germs, toxins, foreign tissue, etc. T lymphocytes are the basis of cell-mediated immunity (CMI) and B lymphocytes are the basis for humoral immunity.

When B cells are stimulated by a foreign antigen they react by transforming into a plasma cell, which then manufactures specific antibodies - proteins specifically tailored to link up with the activating antigen. Antibodies can inactivate the invading organism in four different ways, including agglutination, precipitation, neutralization and lysis. However, these antibody powers are weak and rarely serve to completely repel a foreign invader.

The real power of antibodies comes through activating the complement system, which consists of about 20 interacting enzymes/proteins. When antibodies attach to antigens, they create antigen-antibody complexes, which activate the complement system. The complement proteins can inactivate germs in a multitude of ways. One of the most important occurs when complement proteins attach to the antigen-antibody complex. This new immune complex causes neutrophils and macrophages to ingest the germ to which the antigen is attached. Neutrophils and macrophages (phagocytes) can ingest and digest germs even with antigen-antibody complexes to identify the germs, but the complement/antigen-antibody complex sends them into a feeding frenzy.

With this brief introduction to the immune system, we can now proceed to the exciting research which shows the way to immune rejuvenation. Immunoscience has shown that it's (usually) never too late to restore immune activity to more vigorous, balanced and youthful levels.


Vitamin A: The anti-infective vitamin

Vitamin A, or retinol, is a fat-soluble vitamin that is essential for innate (non-specific) immunity. Vitamin A is necessary for the health of the epithelial (mucous-secreting) cells that line the mouth, nose, throat, stomach, intestines, lungs and urogenital tract, due to its role in mucopolysaccharide production . Without adequate Vitamin A, epithelial cells dry up and harden, then becoming more easily penetrated by bacteria and parasites. The epithelial cells provide one of the chief barrier functions of innate immunity. Also, Vitamin A-deficient epithelial cells don't secrete lysozyme, the enzyme that digests bacteria. Vitamin A was dubbed the anti-infective vitamin in 1928 when two British researchers published a review of human and animal research linking Vitamin A deficiency to impaired resistance to infection.

In a 1994 review article on Vitamin A and immunity, R.D. Semba concluded that Vitamin A deficiency is an immunodeficiency disorder which results in widespread changes in immunity, including pathological impairment of mucous membranes, impaired antibody responses to antigen challenges, alterations in lymphocyte subgroups (ratios of T4, T8 and CTL cells), and altered T and B cell functions. Semba noted that Vitamin A is an immune enhancer that has been shown to increase lymphocyte clonal proliferation responses to antigens and mitogens, increase antibody responses to T cell-dependent antigens, inhibit programmed cell death (apoptosis), and restore the health and function of damaged mucous membranes.

Mega-nutrient pioneer M.D., Robert Atkins considers Vitamin A to reinforce the immune system's resistance to any infectious disease, even AIDS. He reports that some scientists suggest that even a modest Vitamin A supplement of 13,000 to 20,000 IU/day may slow AIDS disease advance. People with AIDS are much more likely than healthy people to have low levels of Vitamin A, even when Vitamin A intake is adequate. Atkins notes that doctors can predict life expectancy of AIDS patients just by measuring Vitamin A blood levels.

High dose Vitamin A supplementation is controversial, as Vitamin A can build up in the liver to toxic levels. In a review of Vitamin A toxicity, Hathcock and colleagues report that in adults, Vitamin A toxicity at supplemental intakes of less than 50,000 IU daily for long periods is rare. They state that ...reports of vitamin A toxicity in adults with supplemental intakes <[less than] 50 000 IU/day mainly involve persons with unusually high dietary intakes or with confounding medical conditions, such as liver disease, malnutrition, or use of drugs or alcohol. They also note birth defects have occurred in pregnant women taking 25,000 IU/day. However, even more recent evidence has suggested that intakes over 10,000 IU Vitamin A/day in pregnant women increases the risk of birth defects, so it is now commonly recommended that women who are pregnant, or who are expecting or trying to get pregnant limit their supplemental preformed (i.e. not counting carotenoids) Vitamin A intake to 5,000 IU/day. For most other reasonably healthy adults, a daily Vitamin A supplement of 10 - 20,000 IU will probably be safe and effective. ( I have used 20 - 50,000 IU Vitamin A daily for 31 years with no signs of toxicity.) Chronic toxicity signs and symptoms include hair loss, anemia, bone pain, brittle nails, dry mucous membranes, edema, fatigue, fever, headache, enlarged liver, insomnia, irritability, muscle pain and stiffness, skin rash or scaliness, vomiting and weight loss.

Some researchers report that getting more than about 6,000 IU of vitamin A itself from food and supplements increases the risk of fractures in people over 50. Beta carotene is safe for your bones, though high doses (more than in a basic multi) may increase the risk of lung cancer in smokers.


Vitamin C: More may be better

Vitamin C (ascorbate or ascorbic acid) is the subject of a massive amount of experimental and clinical research. In a 1984 review article, long time Vitamin C researcher R. Anderson labeled Vitamin C an immunostimulatory, anti-inflammatory, anti-allergic vitamin. Anderson stated that Vitamin C is essential to promote optimal migration of neutrophils and macrophages to infection sites. He notes that high serum levels of Vitamin C increase neutrophil mobility and lymphocyte transformation. Neutrophils and macrophages secrete toxic oxidants - superoxide, hydrogen peroxide, hypochlorite and hydroxyl radicals - to kill germs. Unfortunately, these oxidants leak out of the neutrophils/macrophages, damaging them and surrounding tissue, promoting excessive inflammation, unless neutralized by adequate antioxidants such as Vitamin C. Anderson also reports that Vitamin C enhances neutrophil microbial killing action by multiple chemical pathways. Anderson also notes that many experiments show Vitamin C to enhance T lymphocyte reactivity to mitogens in humans and animals. Vitamin C also lessens allergic reactions at high doses through inactivating histamine.

A 1993 study with 20 healthy adults found that Vitamin C given at a dose of 60 mg/Kg (e.g. 4200 mg Vitamin C for a 70 Kg adult) increased natural killer (NK) cell activity against tumor cells by 129-231%. NK activity peaked 8 - 24 hours post-dose.

In a 1997 follow-up study, the same dose of Vitamin C was used in 55 patients suffering toxic chemical exposure, which often decreases NK activity. Vitamin C increased NK activity 300 to 1000 % in 43 (78%) of the test subjects. Lymphocyte proliferation responses to T and B cell mitogens were also restored to normal in the same 78% of subjects.

In a review of Vitamin C's effect on cold symptom alleviation, H. Hemila noted that there was a 19% decrease in symptom severity in cold studies that used 1 gm Vitamin C/day, with a 29% reduction in symptom severity in studies that used 2 - 4 gm Vitamin C/day. Hemila also commented that ...the diet of our ancestors contained 0.4 - 2g/day of vitamin C, which indicates that such amounts are not unfamiliar to human physiology, i.e. they are not pharmalogical Vitamin C is a cheap and safe nutrient; several of the suspected side effects of fairly large amounts are unfounded.... none of the intervention trials has revealed any significant side effects of the vitamin.

In a 1987 review of Vitamin C safety, J.Rivers reports that most of the alleged dangers of Vitamin C, such as B12 destruction, iron overload in healthy people, mutagenicity and oxalate formation, are simply not shown by the evidence. He does caution, however, that chronic stone-formers, patients with kidney impairment or on hemodialysis should not ingest large Vitamin C doses. He also points out that people who are genetically susceptible to iron overload (hemochromatosis and hemosiderosis) may be adversely affected by long-term high dose Vitamin C.

The available evidence suggests that for most reasonably healthy adults 2 - 10 gm Vitamin C/day, divided into at least 4 doses, should be a safe and effective immune enhancer. If diarrhea or severe gas develops, reduce dosage.

Vitamin E: The antioxidant immunostimulant

Vitamin E is the chief fat soluble antioxidant in human tissues - it is the lipid soluble, chain-breaking free radical scavenger that protects cell membranes. When Vitamin E sacrifices itself to protect polyunsaturated fats in cell membranes, it becomes the tocopheroxyl free radical. This free radical Vitamin E is then reduced back to Vitamin E by Vitamin C. Thus, Vitamin C and Vitamin E act synergistically to protect membranes from lipid auto-oxidation and play a key role in protecting phagocytes from damage by self-generated free radicals, since immune cells have a high percentage of easily oxidised fatty acids in their membranes. Phagocyte membrane auto-oxidation is a major immune problem - so much so that neutrophils typically die from oxidant auto-oxidation after killing just 3 - 20 bacteria.

A study from Cambridge University, published in the Lancet in 1996, for in-stance, found that among men with heart disease, 400 to 800 IU of E supplements a day for an average of 1.5 years substantially reduced the risk of heart attack, but not death rates. (Later, however, the researchers reanalyzed the data and did find that vitamin E markedly reduced deaths from coronary artery disease.)

A 1991 experiment found that 800 mg synthetic Vitamin E given to healthy people for 60 days before undergoing an eccentric exercise test prevented the exercise-induced rise in IL1, a major inflammatory cytokine involved in over-strenuous exercise muscle damage. Vitamin E also reduced IL6 production, a cytokine that suppresses cell-mediated immunity.

In a 1988 review of Vitamin E safety, Bendich and Machlin looked at all the human double-blind and large population Vitamin E supplementation studies published since 1975. They stated that ... the toxicity of vitamin E is low and ... the vitamin is not mutagenic, carcinogenic, or teratogenic.... few side effects have been reported, even at doses as high as 3200 mg/day (3200 IU/day). Thus, a daily supplement of 200 - 800 IU natural Vitamin E (as Vitamin E succinate, mixed tocopherols, or d-alpha/gamma tocopherol) is a reasonable, safe, immunoenhancing dose for most people.

Vitamin B6: RDA is too low

B6 has widespread effects on immune function in animal studies. B6 deficiency leads to thymus atrophy and lymphocyte depletion in lymph nodes and spleen in monkeys, dogs, rats and chickens. In animals B6 deficiency leads to reduced antibody production, delayed type hypersensitivity reaction, T cell cytotoxicity (germ-killing), and reduced response of lymphocytes to T cell mitogens . Depletion of B6 in humans decreases antibody production and reduces blood lymphocyte levels.

B6 is necessary for the production of cysteine, the rate-limiting amino acid for production of glutathione, a critical cell and immune biochemical. Glutathione prevents the activation of nuclear factor kappa B (NFKB) by reducing intracellular oxidant load. NFKB activates inflammatory cytokine production, especially immunosuppressive IL6. A vegetarian diet, typically low in both cysteine and B6, can be expected to be anti-immune health at least through this pathway.

Scientists aren't sure why high blood levels of vitamin B6 protect against colon and colorectal cancers, but some scientists report that individuals who have high levels of B6 have less chance of having damaged DNA, which can lead to cancer.

B6 dosages of 100 mg or less are generally considered safe. A 50 - 100 mg B6 supplement is thus a reasonable way to increase immunocompetence. B6 is best taken with other B vitamins.

CoQ10 or idebenone?

Coenzyme Q10 (CoQ10) is absolutely critical to life. No mitochondrial production of ATP bioenergy can be produced without it. And without ATP there is no life. CoQ10 is also an important antioxidant. Lester Packer, a leading antioxidant researcher, believes CoQ10 is one of the 5 main cellular antioxidants that mutually reinforce and regenerate each other. Immune cells generate massive levels of oxidants which often poison themselves and surrounding cells. Also, high oxidant levels lead to increased inflammatory cytokine activity, and excessive inflammatory activity suppresses immunity.

CoQ10 is an effective antioxidant only in its reduced, i.e. non-oxidised form. Weiland and colleagues report that (idebenone), a synthetic [Co] Q10 derivative, is known to have greater antioxidative capacity than [Co] Q10, which is not restricted to the reduced form of the molecule. In our experiments, idebenone was far more effective than Q10 in preventing oxygen radical-mediated damage to microsome lipid and proteins.... idebenone is non-toxic to humans and has been used successfully in the therapy of patients suffering from a variety of neurological disorders.

A supplement of at least 100 mg CoQ10 and and/or 90 mg idebenone is a safe and useful immune booster.


Garlic

Garlic is one of the most medicinal plants in the world. The extracts of Allium sativum bulb and compound preparation possess pharmacodynamic properties. Garlic is used as a carminative, aphrodisiac, expectorant, and stimulant. It has been respected for decades for its anti-cancer actions, circulatory effects, antimicrobial actions, and its effects on hypertension and digestive/skin disorders.

The extract of garlic was found to have a significant protective action against a fat induced increase in serum cholesterol and plasma fibrinogen and in fibrinolytic activity. There are two main medical ingredients which produce the garlic health benefits: allicin and diallyl sulphides. However the antioxidant properties of garlic compounds are represented in four main chemical classes, alliin, allyl cysteine, allyl disulfide, and allicin, prepared by chemical synthesis or purification. Several studies have revealed and characterized a molecular mechanism by which allicin blocks certain groups of enzymes. The role of allicin in warding off infection and strengthening the immune system may be particularly valuable in light of the growing bacterial resistance to antibiotics. It is unlikely that bacteria would develop resistance to allicin because this would require modifying the very enzymes that make their activity possible.
Recent research from Pennsylvania State University suggests that the natural chemicals found in garlic can suppress tumours, and may even help to prevent cancer. Meanwhile, scientists at the Chelsea and Westminster Hospital, in London, have discovered that taking garlic during pregnancy reduces the risk of pre-eclampsia (raised blood pressure and protein in urine).

A recent study also finally confirmed that there is something in the "garlic for colds" theory after all. The study, carried out by Peter Josling, a chemist and founder of the Garlic Centre, based in East Sussex, shows that a new type of garlic supplement, Allimax, which contains high doses of allicin, can help strengthen the immune system and minimise the effects of the common cold.

When 146 volunteers were monitored over a three-month period, it was shown that the group taking a daily garlic capsule (containing 180mg of allicin) had only 24 colds in all, compared to 65 colds in the placebo- taking control group. The garlic group also recovered three times as quickly. "This study proves that allicin has powerful antiviral and antibacterial properties," says Josling.


As with almost anything, there are a few people who are allergic to or otherwise intolerant of garlic. Low level allergies can result in heartburn, flatulence, etc. If you suspect you might have an allergy to garlic consult your doctor or a qualified allergy specialist. Symptoms of garlic allergy include skin rash, temperature and headaches. Also, garlic could potentially disrupt anti-coagulants, so it's best avoided before surgery.

Dosages for whole garlic clove are 2 to 4 grams per day of fresh, minced garlic clove (each clove is approximately 1 gram). Dosages for capsules or tablets of freeze-dried garlic standardized to 1.3% alliin or 0.6% allicin: 600 to 900 mg daily.



Glutamine

Glutamine is highly in demand throughout the body. It is used in the gut and immune system extensively to maintain optimal performance. 60% of free-form amino acids floating in skeletal muscles is L-glutamine. L-glutamine plays a very important role in anabolic metabolism, and it appears to be a very important nutrient for anybody interested in maintaining or building lean muscle tissue.

Since the body relies on glutamine as cellular fuel for the immune system, scientific studies have shown that glutamine supplementation can minimize the breakdown of muscle tissue and improve protein metabolism. Its effects on replenishing the body after stress or trauma have been shown in Europe where it is commonly given to patients in hospitals. Glutamine's cell-volumizing effects have also been shown in several studies. A study done in 1995 by LSU College of Medicine showed that a surprisingly small oral dose of 2 grams of glutamine raised GH levels more than 4X over that of a placebo. Age did not diminish the response of the volunteers who ranged in age from 32 to 64 years.

Glutamine is the primary source of energy for the various cells of the immune system. Strenuous exercise, viral and bacterial infections, and stress in general cause glutamine depletion that starves the immune cells. Up to 40 grams per day can be used to sustain the immune systems of AIDS or cancer patients undergoing bone marrow transplantation. Very ill patients suffer both a decrease in glutamine levels and muscle loss. The use of glutamine has been documented to aid the survival of severely ill surgical and burn patients. It also speeds up wound and burn healing and improves recovery in general.

In addition, glutamine is a substrate for glutathione, an amino acid which acts as one of our master antioxidants and helps enhance the immune function. Large doses of glutamine stimulate the immune response even under heavy stress.

Other supplemental benefits of glutamine include: improving brain function; stabilizing blood sugar; helping heart function; maintaining the health and functioning of the gut lining; decreasing alcohol cravings; decreasing sugar cravings; helping with with wound healing; helping maintain proper acid/alkaline balance; possible cancer benefits.

There are no side effects associated with L-glutamine, because it is a nutrient naturally occurring in the body. Reports of an upset stomach are associated with ingesting a great deal of glutamine, using smaller doses is recommended if this occurs. Dosages of 2-5 grams (twice daily) on an empty stomach is sufficient for healthy sedentary people to boost immune system function

Zinc: Thymic rejuvenator

Zinc is a trace mineral often in short supply in the diet. As mentioned previously, a 1993 study of elderly adults found their zinc intake 40% below the 1980 U.S. RDA. Bogden and colleagues reported that greater than 90% of healthy elderly subjects had zinc intake below the RDA. Zinc deficiency is hardly a rare phenomenon.

Zinc is essential for the integrity of the thymus gland and for cell-mediated immunity. The thymus incorporates zinc into the inactive form of thymulin, a thymic hormone, creating active thymulin (ZnFTS). ZnFTS is necessary for the maturation and differentiation of stem cells into mature T cells. T lymphocyte responsiveness to mitogens is increased by zinc. Mocchegiani and coworkers reported that 90 days of zinc supplementation in mice caused a regrowth of atrophied thymus, with renewal of both hormone-secreting cells and T cell-processing cortex cells. An increase in natural killer cell activity also occurred.

Extremely high zinc doses (300 mg/day) can reduce the copper level in the body and be immunosuppressive , but 50 mg or less daily doses are generally considered safe. A 20 - 50 mg daily zinc supplement as zinc orotate, zinc monomethionine, or zinc ascorbate is a generally safe and useful immune booster.

Selenium: IL2 enhancer

The trace mineral selenium (Se) is best known for its role in activating the crucial antioxidant enzyme glutathione peroxidase (GSHPx) . Se-GSHPx uses glutathione (GSH) to break down hydrogen peroxide into water and oxygen, protecting cells from oxidant molecules that are produced from immune activation. GSHPx activity in liver and plasma and serum is very sensitive to body selenium levels. GSHPx/GSH are key antioxidant factors necessary to minimize the activation of NFKB, the nuclear factor that activates excessive production of oxidants and inflammatory cytokines, which are immunosuppressive at excessive levels. Diminished Se-status and excessive NFKB activation is a major factor in moving HIV-infected people into full-blown AIDS.

Selenium is a potentially toxic mineral causing symptoms, including nausea, diarrhea, fatigue, nerve damage, hair loss and nail changes. Selenium expert R. Passwater notes that organic forms of selenium are toxic at levels in the vicinity of 3,500 micrograms (3.5 milligrams) daily. Inorganic forms of selenium may be toxic at one-third that level. However, intakes up to 200 mcg/day are generally considered safe, and Passwater notes many Japanese average 600mcg daily, and Greenlanders may ingest 1300mcg/day. A supplement of 100-200 mcg Selenium/day, as selenium yeast, selenomethione, or sodium selenite/selenate, should be an excellent booster of cell-mediated immunity which declines with age.


Acetyl-L-Carnitine: Not just a nootropic

Acetyl L-Carnitine is a nootropic nutrient familiar to life extension enthusiasts. It is used to regenerated age-related deficits in mitochondrial function, as well as to enhance brain levels of the key neurotransmitter acetylcholine. Yet recent reports suggest Acetyl L-Carnitine to be an enhancer of cell-mediated immunity as well. Jirillo and colleagues gave either placebo or 2gm Acetyl L-Carnitine/day for 30 days to 20 active pulmonary tuberculosis patients.

In a 1989 book on stress, immunity and aging, two studies with Acetyl L-Carnitine were included. One study found a reduced decline of macrophage phagocytic and cytotoxic capabilities in aged rats treated long-term with Acetyl L-Carnitine The other study reported an increase in PHA mitogen induced T lymphocyte proliferation in elderly people treated with Acetyl L-Carnitine . Immune rejuvenation can now be added to Acetyl L-Carnitine's potential for mitochondrial and neuroendocrine regeneration. 1 gm Acetyl L-Carnitine twice daily is a safe and useful dose for all three.

Resveratrol: PGE2 inhibitor
Resveratrol is a phenolic compound that contributes to the antioxidant potential of red wine, where trans-Resveratrol concentrations may reach 15 mg/L . According to Fremont, major biological activities of Resveratrol include inhibition of membrane lipid peroxidation (important for optimal phagocyte activity), free radical scavenging, alteration of eicosanoid (prostaglandin) synthesis, anti-inflammatory and anticancer activity . Trans-Resveratrol in combination with vitamin C and/or E was more effective in protecting cells from oxidant stress than was any of the three antioxidants alone. The results of the experiment showed Resveratrol was not only antioxidant and antimutagen, but could also reduce oxidant-caused cell death . Resveratrol was shown to inhibit production of nitric oxide and tumor necrosis factor alpha (TNF-A) by lipopolysaccharide-stimulated Kuppfer cells. Kuppfer cells are macrophages fixed in place in the liver. Their chronic overproduction of No and TNF-A due to chronic infection can cause severe liver damage .

Perhaps Resveratrol's most important property is its ability to inhibit cyclooxygenase-2 (CoX-2) . Prostaglandin E2 (PGE2) is the chief inflammatory prostaglandin. PGE2 is produced from arachidonic acid (a polyunsaturated fatty acid) via the CoX-2 pathway. Macrophage- and splenocyte-derived PGE2 levels are greatly increased with age. Furthermore, PGE2 favors production of Th2-associated cytokines (IL-4 and IL-5) while suppressing Th1-associated cytokines (IL-2 and IFN-G), a pattern analogous to immune senescence. Inhibition of cyclooxygenase can restore PGE2 levels to normal.

In addition, trans-Resveratrol has been shown to modulate the activity of polymorthonuclear leukocytes (PMN) - mainly neutrophils. Trans-Resveratrol interfered with the release of inflammatory mediators by activated PMN. Excessive release of inflammatory mediators by germ-stimulated neutrophils inhibits cell-mediated immunity.

In a study using commercial grape juice with trans-Resveratrol added at a level of 4 mg/litre consumption of the beverage by healthy subjects for 4 weeks led to positive effects on platelet aggregation and thromboxane production, compared to no such effect in those drinking the same commercial grape juice without added Resveratrol. This experiment proved 1) that trans-Resveratrol is absorbed in biologically active quantities; and 2) the dose of trans-Resveratrol provided by the spiked grape juice was only 2 mg - therefore even modest quantities of trans-Resveratrol have significant biological activity. As an immune synergist with C and E, 5 - 40 mg/day of trans-Resveratrol may be a useful part of any immune program.

Additional good news is that resveratrol may also be effective in fighting other human amyloid-related diseases such as Huntington's, Parkinson's and prion diseases. Studies by a group at the Institut National de la Santé et de la Recherche Médicale in Paris, France headed by Christian Néri have recently shown that resveratrol may protect neurons against amyloid-like polyglutamines, a hallmark of Huntington's disease.


Pyritinol: Pro-immune nootropic

Pyritinol, also known as pyrithioxine or dipyridoxine disulphide, is almost identical to vitamin B6, but it has no B6 activity. Pyritinol has been used to treat dyslexia, post-stroke states, cerebral trauma, attention deficit disorder, etc. since 1961. Pyritinol has been shown to be a powerful antioxidant, quenching the most toxic free radical, the hydroxl radical, formed through interaction of superoxide and hydrogen peroxide : All three of these oxidants are secreted by activated neutrophils and macrophages to kill germs. As Pavlik and Pilar remark in their report on Pyritinol's antioxidant activity: The most dangerous [kind] of oxygen radicals is the hydroxyl radical that can attack proteins, lipids, nucleic acids and actually, almost any molecule of a living cell: Unfortunately, the human body has no enzymatic defense against hydroxyl radicals, as it does for superoxide and hydrogen peroxide. Vitamin C and cholesterol are the two main hydroxyl quenchers for humans.

A 1991 report cites oxygen radicals as the main cause of damage in viral influenza in mice, and points out that in viral disease such as viral hepatitis, AIDS, dengue fever, measles and herpes diseases, the virus damage to cells was minimal. The main damage to cells is actually caused by the oxygen radicals released by activated neutrophils and macrophages. The researchers examined neutrophils/macrophages in influenza-infected mouse lungs and found an 800% increase in superoxide production compared to non-infected control mice. The researchers noted that superoxide is not particularly toxic to many cells and pathogens, and that it was more likely the hydroxyl radicals generated from superoxide/hydrogen peroxide release by the lung neutrophils/macrophages that was causing the lung damage. Thus, Pyritinol, along with vitamin C, may have a useful role in fighting viral disease by quenching hydroxyl radicals.

A 1993 Pyritinol study found that Pyritinol enhanced neutrophil mobility . Not only is the neutrophil ability important for getting them to infection sites, it's important to help them survive and leave infection sites. Anderson remarks that antioxidants [that quench hydroxyls] such as ascorbate [and Pyritinol] may prevent immobilization of inflammatory cells [neutrophils/macrophages] by inhibiting auto-oxidation of the cell membrane. These cells, especially neutrophils, therefore may enter the inflammatory zone, phagocytose [eat germs] and depart without contributing to the development of chronic inflammation. Normally, neutrophils are quickly immobilized at infection sites in massive numbers (they comprise 60% of white blood cells), where they die from self-poisoning by their own secreted oxidants, then becoming (collectively) the pus that forms in wounds. Thus vitamin C and Pyritinol have the potential to increase the useful germ killing power of neutrophils, while reducing the inflammatory damage they inflict on wound sites or inflamed tissue (as in rheumatoid arthritis, which Pyritinol is used to treat.

Pyritinol is a very well tolerated drug, with only occasional skin rash or gastric upset noted as side effects. Pyritinol should only be used with physician monitoring by rheumatoid arthritis sufferers, as there are occasionally side effects from Pyritinol in rheumatoid arthritis patients. A daily dose of 100-300 mg Pyritinol should serve as a generally safe and effective antioxidant, nootropic immune booster.

Thymus extract: Tonic for the aging thymus gland

The thymus gland is the master gland for cell mediated immunity. T lymphocytes are processed in the thymus cortex to mature them into the various T cell types, and to destroy T cells that might attack the body . The thymus gland also secretes various hormones, including zinc-thymulin, thymosin, thymopoietin, and thymus humoral factor . Unfortunately, the thymus tends to atrophy early in life, usually by age 20, and with advancing age, the thymus turns from a well-structured organ to a few sparse lymphoid lobules within a fat tissue. . As noted earlier, vitamin A can help regrow thymus structure, and zinc can re-activate zinc-thymulin secretion. Thymic extracts may serve to regenerate thymic structure and replace the variety of thymic hormones, since properly prepared thymus extracts contain the whole range of the polypeptide hormones.

Since animal experiments and human research have found no single thymic hormone to be capable of performing all the immune-optimizing functions induced by the whole family of thymic hormones, a pharmacologically balanced thymus peptide mixture is both more natural, and more likely to be safe and effective, than any one thymic hormone.

DHEA: Cell mediated immune booster

DHEA (dehydroepiandrosterone) is an adrenal steroid hormone that decreases radically with age. DHEA levels peak around age 25, decrease 60% by age 50-60, and drop to 20% of maximum by age 70 . DHEA is antiglucorticoid (anti-cortisol), due to its down-regulation of glucocorticoid (GC) receptors . Since GCs are immunosuppressive (4,70,71), DHEA's immunostimulant role is due at least in part to its counter-regulatory action opposing GC action. Thus Khorram and colleagues note: The 4-fold increase in DHEAS/cortisol ratio in response to a 50 mg dose of DHEA as seen in our age-advanced male cohort may thus be viewed as favorable adrenal hormone milieu for up-regulating immune function.

Both human and animal studies show similar effect of DHEA in boosting immune function. Perhaps the most important benefit of DHEA is increasing IL2 output in aging individuals. Khorram and co-workers reported a 50% increase in IL2 output in mitogen-stimulated T cells in DHEA-treated aged men . IL2 is the basis for the cell-mediated TH1 type immunity that declines with age . Suzuki and colleagues also noted the DHEA-stimulated increase in IL2 production, with increased cytotoxic effect, in human T cells treated with typical youthful blood of DHEA . They also point out that ...DHEA represents the only naturally occurring hormone to up-regulate IL2 secretion.

DHEA has also prevented thymus gland involution in mice treated with the synthetic GC dexamethasone. DHEA has increased both numbers and cytotoxic activity of natural killer cells in humans. Administration of 200 mg/day of DHEA for 3-6 months significantly reduced corticosteroid requirements in patients with lupus erythematosus.

A reasonable DHEA dose for women would be 5-25 mg/day, with 25-50 mg/day being a more suitable male dose. 7-keto DHEA doses of 12.5-50 mg for women, or 25-100 mg for men, would also be a reasonable immune-boosting doses.

Melatonin: More than a sleeping pill

Melatonin is a hormone produced by the pineal gland (a small gland inside the brain) that decreases with aging. Melatonin's most widely known role is in regulating the sleep-wake cycle, and has been widely used as a sleeping pill since the 1990s. Melatonin secretion peaks around age 10, drops to half its peak level by age 25, one-fourth peak level by 35, and drops to 10% peak level by age 50. Melatonin is a powerful hydroxyl radical scavenger, and is more than twice as effective as vitamin E at scavenging peroxyl radicals.

While melatonin does aid sleep in a certain group of people whose biological clocks are out of kilter, researchers found it doesn't promote sleep among the most common users of the supplement -- those suffering from jet lag or weary shift workers.

Melatonin expert P. Rozencwaig believes that although melatonin is generally non-toxic, certain people should not use melatonin. His list includes pregnant women, women trying to get pregnant; manic depressives or schizophrenics; normal children; severe autoimmune disorder cases (rheumatoid arthritis, lupus, etc.); and those with immune cancers such as leukemia or lymphoma.

Conclusion

Either we must negate entropy, or entropy will negate us! A weak immune system is typical of normal' old age, and leads to the sickness, debility and death that is typical of normal old age. The 16 supplements discussed in this article provide us with the ammunition needed to vanquish the microbial and cancerous agents of entropy, as much as it's in our power, and to maintain a youthful (powerful and effective) immune system well into old age.

You don't have to be a victim - the choice is yours! And since each of the supplements has many pro-immune effects, even a small subset of the 16, such as DHEA, melatonin, garlic, glutamine and zinc, may provide significant immune benefits. Take as many of the 16 supplements as you see fit - they all provide general health and anti-aging benefits, beyond their immune enhancing effects.

16 Immunity Enhancers At A Glance

Vitamin A - 5000-20,000mg IU Breakfast or lunch
5000 IU (Women pregnant or attempting pregnancy)

Vitamin C - 500-2000mg 4-6 times daily

Vitamin E - 200-800 IU Daily with fat-containing meal

Vitamin B6 - 25-50mg Breakfast and lunch
(take with 10-100mg B1, B2, B3, B5)

CoQ10 - 100-200mg With fat-containing breakfast or lunch

Glutamine - 2-5g (2 times daily) AM and PM on empty stomach

Garlic - 1.3% alliin or 0.6% allicin: 600 to 900 mg daily.

Idebenone - 30-60mg Breakfast and lunch

Zinc - 20-50mg Breakfast or lunch

Selenium - 100-200mcg Breakfast or lunch

Acetyl L-carnitine - 1000mg AM and PM on empty stomach

Resveratrol - 5-20mg Breakfast and lunch

Pyritinol - 100mg 1-3 times daily

7-Keto DHEA - 12.5-50mg (women) Upon arising

7-Keto DHEA - 25-100mg (men) Upon arising

Melatonin - 2-6mg Bedtime

Thymus Extract - Dosage varies depending on mixture


비타민 A,
비타민 C,
비타민 E,
비타민 B6,
코엔자임 Q10,
글루타민,
마늘,
Idebenone,
아연,
셀레늄,
아세틸 L 카르니틴,
베라 트롤,
Pyritinol,
7 케토 DHEA,
멜라토닌,
흉선 추출물

• More articles on our Immune System
• Answering Your Questions About Immunity

Reference Sources: James South, MA, Susan McHilley, ND, Matthew Kendall, ND