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Originally Posted by hackskii Defencies in zinc and you will have low test levels too.
Zinc is also a natural aromatase inhibitor too, not to any extent I am sure but It is. |
A Cut & Paste on Zinc.
Aging and Immunity
By James South, MA
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 "ageing." The anti-ageing 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-ageing 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" (1), and "Nutritional deficiencies are seen in at least one-third of the elderly in industrialized countries." (2) Overeating and obesity, now epidemic in the Western world, also decrease immune function. (2) Stress is also a major assault on immune health. (2) Indeed, the stress hormones cortisol/corticosterone are sometimes used in experiments to weaken the immune system (3) Perhaps the most inevitable entropic weakener of our immune vigor is aging itself. Ageing 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.... Altered B cell function also occurs with aging...." (4)
Fortunately, modern science has discovered many nutrients, hormones and anti-aging drugs that we can use to combat the otherwise inevitable entropic destruction of our priceless immune health. Many different immune boosters are needed to optimize immune power throughout life, even into old age, because there are so many facets of immune function that decay with age. Immuno-suppressive PGE2 levels increase with age, even in healthy aged adults. (5) "One of the biological changes associated with aging is an increase in free radical formation with subsequent damage to [immune] processes." (5) Active thymulin, one of the most important thymus gland hormones for T cell activity, "disappears from blood circulation by the 5th - 6th decade in humans." (5) "... after primary immunization, antibody responses of aged individuals are characterized by lower, slower, and shorter responses than those observed in young subjects." (7) "Normal aging in human beings is associated with increased basal IL-6 [interleukin-6] production by lymphocytes .... Dysregulation of this cytokine with increased basal secretion has been proposed to contribute to ... age-associated diseases such as B cell lymphoma, osteoporosis, and Alzheimer's disease." (45) And these are just a few of the many immune parameters that weaken with age!
A program consisting of various vitamins, minerals, hormones and anti-aging drugs 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. In order to better understand the power of a pro-immune supplement program to restore immune health, it is first necessary to have a basic overview of our immune system.
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. (13)
Human natural immunity makes us resistant to such diseases as animal paralytic viral infections, hog cholera, cattle plague and canine distemper. (13)
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." (13)
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. (13)
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 protein C3a attaches 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." (13)
CMI, or T lymphocyte immunity, is partly independent from, but also interacts with, humoral immunity. T cells have receptors (TCR) on their surface that can react with foreign antigen. TCRs cannot recognise antigens directly. Macrophages must first attack and digest a given pathogen into protein (antigen) fragments. The macrophage then presents the antigen to the TCR of a nearby T lymphocyte. Until the TCR of a T cell is activated by a specific antigen, the T cell can potentially react to thousands of different antigens. Once a T cell is antigen activated, it begins reproducing itself by cloning. This is called "proliferation." The cloned T cell copies can now react only to the specific antigen (e.g. a Candida membrane protein), their progenitor first reacted to. This allows rapid production of massive numbers of T cells focused on destroying the specific pathogen currently threatening the body. Some of the activated T cells will become memory cells, (so also will some of the activated B cells), put in storage as a "rapid reaction force" should the same antigen show up again in the future. (13)
T cells occur in one of 3 forms: T helper cells (T4 or CD4+), T suppressor cells (T8 or CD8+), and cytotoxic T lymphocytes (CTL). T8 cells help reduce immune activity so that it doesn't go to excess. Ideally proper T8 activity prevents auto-immune disease. CTLs directly attack and destroy pathogens which have the antigen a CTL has been activated toward. (13)
T4 helper cells come in 2 varieties. Helper cell type 1 (TH1) is the booster/activator of cell-mediated immunity. Helper cell type 2 (TH2) is the activator of B cell antibody production. Both TH1 and TH2 cells do their helper/activator work through secretion of immune proteins called "cytokines" or "lymphokines." There are at least 17 different cytokines. TH1 cells produce interleukin-2 (IL2), interferon gamma (IFN-G), and tumor necrosis factor alpha (TNF-A). IL2 activates CTL, T8 cells, and natural killer cells. TH2 cells produce IL4, 5, 6, and 10. IL4 activates plasma cell antibody production and inhibits TH1 cells. (14)
"Immune senescence [aging] is characterized by specific cytokine changes that favor Th2 T-helper responses (antibody production, including auto [self] antibody production) while suppressing Th1 responses (cytotoxic T cell and macrophage activation, i.e. cell-mediated immunity." (15) TH1, cell-mediated immunity (CMI) is more effective (and youthful) immunity; TH2 antibody-dominated immunity is less effective and more troublesome, due to autoimmune disease (and typical of aged immunity). Unfortunately, the main stimulator of TH1 CMI is thymic hormones (16), yet thymic hormones decrease radically with aging. (6-9)
Another key determinant of immune power is the T4:T8 cell ratio. (17) Too many T8 cells tends to suppress CMI; not enough T8 cells allows CMI to run rampant, with possible damage to the body itself. The ideal T4:T8 ratio is about 2:1; less than 1:1 represents serious immune weakness. (17) Thymic hormones tend to normalize T4:T8 ratios in a broad range of conditions, including HIV infection, atopic dermatitis, chronic bronchitis, recurrent respiratory infections, viral hepatitis and rheumatoid arthritis. (17)
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.
Nutrient and the immune response
As noted previously, malnutrition is the main worldwide cause of immunodeficiency, and nutrient deficiencies are common in industrialized countries. A 1993 Detroit study of healthy, ambulatory elderly people found a mean zinc intake of 9mg/day, 40% below the 1980 U.S. RDA (recommended dietary allowance) of 15mg. Zinc levels in neutrophils and lymphocytes were significantly lower than those of control subjects (15). A Belgian study of selenium status in institutionalized adults found the daily selenium intake averaged only 40 mcg, less than the U.S. "safe and adequate" intake range of 50-200 mcg/day (18). In a study of immune function in elderly patients receiving nursing care as a result of stroke, but who had no active medical problems at the time of study, 22% were vitamin A-deficient and 48% were vitamin C-deficient (19). These results are typical of modern dietary studies, showing many people, especially the elderly, to be nutrient-deficient even by (modest) RDA standards, and RDA levels are far below so-called "optimum dietary allowance" or "therapeutic" nutrient levels.
Not surprisingly, therefore, even research studies using modest nutrient amounts have yielded positive immune-enhancing results. In a 1992 study Chandra gave elderly subjects a low-potency multivitamin/mineral supplement or placebo. The nutrient levels were set at 50-300% of the U.S. RDA. After 12 months, technical measures of immune response were enhanced in the supplement group. T-helper cell levels, natural killer cell activity, T cell proliferation in response to mitogens (artificial experimental antigens), and IL2 and IL2 receptor levels all increased significantly, with no change in the placebo group. And these technical measures of immune improvement were correlated with clinical benefits. The mean number of days of infectious illness was 23 for the supplement group vs. 48 for the placebo group. Antibiotics were used for a mean of 18 days in the supplement group vs. 32 days in the placebo group (20).
In another study 30 elderly patients were supplemented with vitamins A, C, and E or placebo. The supplement group got 8000 IU A, 100 mg C and 50 mg E. These levels are about 1 2/3 the 1980 U.S. RDA for each of these nutrients. " Following 28 days of supplementation with ... vitamins A, C and E there was a distinct improvement in cell-mediated immune function. In particular, the number of T cells, T4 cells and the T4:T8 ratio increased significantly. The responsiveness of lymphocytes to the mitogen PHA also increased significantly .... In contrast, no significant change was noted in the immune function of the placebo group." (19)
What these two modest-dose multi-nutrient studies show is that even low-level nutrient supplementation can provide immune enhancement, based both on technical measures of immune function, as well as clinical benefit in the Chandra study. They also show that a combination of nutrients may be synergistic, even though most published studies focus only on a single nutrient, hormone or drug to boost immunity. We shall therefore review a range of immune studies with various nutrients, hormones and anti-aging drugs, with the aim of compiling a comprehensive program to promote "super-immunity."
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 (21). 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. (21) 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. (22)
In a 1979 study, surgery patients were treated with Vitamin A for 7 days before surgery. They were given 300 - 450,000 IU Vitamin A/day. (The 1980 U.S. RDA for Vitamin A is 5000 IU) T lymphocyte counts were taken at 1 and 7 days post-surgery. T lymphocyte counts rose by day 7 in the Vitamin A group, while surgery patient controls not given Vitamin A suffered the usual post-surgical severe T cell immunosuppression. No Vitamin A-toxicity symptoms were observed in the Vitamin A patients. (23)
In 1973, Seifter and colleagues reported a thymotrophic action of Vitamin A in stressed mice. Animals were stressed for 3 or 7 days through partial-body cast. Control mice ate normal lab chow, while Vitamin A mice got extra Vitamin A one day in advance of stressing. "Non-stressed mice had thymus: body wt. ratios of 0.18; stressed mice values were 0.12, while stressed mice receiving vitamin A had values of 0.16. Vitamin A also speeded the rate of thymus weight recovery after the stress was removed. In non-stressed animals vitamin A elevated the thymus: body ratio to 0.22." Seifter thus concluded that Vitamin A had a thymus-protecting effect. (24)
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. (25)
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. (26)
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." (27) They also note birth defects have occurred in pregnant women taking 25,000 IU/day. (27) 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. (28) 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. (27)
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. (29) 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. (29)
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. (30)
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. (31)
In 1997 Prinz and coworkers reported the effects of 75 days of 1 gm Vitamin C supplementation during the winter season on 25 healthy university students. 20 similar control subjects got no Vitamin C. Serum antibody (IgA, IgM, IgG type antibodies) and complement protein C3 (which reacts with antigen-antibody complexes to stimulate neutrophil/macrophage antimicrobial activity) levels were measured on day 1 and day 75. There was no change in IgA levels in the Vitamin C group, while control IgA levels dropped 15%. For IgG, there was no change for controls, but a 15% increase for the Vitamin C group. For IgM levels, controls dropped 8% while the Vitamin C group rose 20%. For C3, controls lost 10%, while the Vitamin C group increased 15%. This experiment showed Vitamin C's ability to enhance neutrophil/macrophage microbe-killing. (32)
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." (33)
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. (34)
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". (35) 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. (35) 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 (35). 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 1998 study gave 30 women (average age 72) 1000 mg ASC and 200 mg Vitamin E daily for 16 weeks. 10 were healthy controls, 10 suffered from heart disease (CHD) and 10 had major depressive disorder (MDD). The study found a 60 - 70% drop in serum lipid peroxides in the MDD and CHD groups, and significant increases in neutrophil adherence, chemotaxis/migration and phagocytic activity in all 3 groups. The phagocytic index - how many germs a neutrophil can kill before dying itself - rose 260% in the controls, 225% in the MDD group, and 1000% in the CHD group. The vitamins also lowered superoxide production in all 3 groups - a good thing, as aging usually leads to a major increase in superoxide production in phagocytes. (37) Excessive neutrophil superoxide production shortens their germ-killing lives. The study also found a massive increase in lymphocyte proliferation in response to mitogen testing in all 3 groups. There was also a modest drop in serum cortisol in all 3 groups, especially large in the CHD group - cortisol being an immunotoxic stress hormone that often increases with aging. (37)
In 1990 Meydani and coworkers gave 32 healthy older adults either placebo or 800 mg synthetic Vitamin E for 28 days. They found that in the Vitamin E group 1) Vitamin E content of plasma, macrophages and lymphocytes was significantly increased; 2) there was a significant increase in delayed type hypersensitivity - a skin
test that measures cell-mediated immunity; 3) IL2 production and mitogen response to optimal doses of ConA were increased; and 4) PGE2 (an immunosuppressive prostaglandin) production and plasma lipid peroxides were reduced. The decreased PGE2 production was especially noteworthy, as PGE2 tends to increase in aged individuals. Lymphocytes from elderly people are more sensitive to the immunosuppressive effects of PGE2. Macrophages from healthy elderly people make more PGE2 than those from healthy young people, and PGE2 suppresses production of IL2, the most critical cytokine for T lymphocyte activity. (38)
In a 1998 study on mouse macrophages, Vitamin E was shown to increase macrophage adherence - the first step in macrophage migration to an infection site. Vitamin E also stimulated chemotaxis and random migration of macrophages - the two processes by which they get to infection sites. Vitamin E also significantly increased the macrophage phagocytic index - the ability of macrophages to ingest germs. Since macrophages are necessary to antigenically activate T lymphocytes, this Vitamin E increase in macrophage activity would presumably benefit cell-mediated immunity, as well. (35)
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. (12)
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)". (39) 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
A 1990 study of U.S. vitamin B6 intake found that 71% of men and 90% of women consumed less than the 1980 RDA for B6. (40) Yet even if most people got the RDA for B6 (2 mg), this would not necessarily be enough for optimum immune health, Karl Folkers, M.D., Ph.D., has published a biochemically-based methodology to establish a more realistic RDA for B6. Folkers noted that B6, in its active form of pyridoxal-5-phosphate, is required to activate a blood enzyme known as EGOT. The specific activity (SA) of EGOT could be correlated with varying B6-intake levels. Folkers discovered that a maximally B6-saturated EGOT enzyme SA is approximately 0.7. Folkers tested 17 people who had no overt B6 deficiency symptoms and determined their EGOT SA levels before and after B6 doses of 2, 25 and 50 mg. The initial mean EGOT SA level was 0.35. After 12 weeks of 2 mg B6, the SA level increased only slightly to 0.45. With a dose of 25 mg B6, EGOT SA rose to 0.64, but 6 of 13 subjects at that dose still had SA of only 0.5 - 0.6. At a dose of 50 mg for 7 subjects, every one showed a SA very close to 0.7, the "ideal" level. Folkers' research showed that even for "well" patients a more realistic B6 RDA is 25 - 50 mg.
In line with Folkers' ideas, Talbott and colleagues gave 11 elderly people 41 mg B6 daily for 4 months. 4 subjects got placebo. Immune measurements were made in all subjects before and after supplementation. After one and two months, plasma levels of active B6 increased about 500% in the B6 group, with no change in the placebo group. Lymphocyte proliferation in response to three different mitogens increased significantly. T4 helper cells increased in number in the B6 group, but not T8 suppressor cells. "These results suggest that improving B6 status is important in stimulating immunocompetence in the elderly." (42)
Folkers and colleagues conducted a study on the effects of CoQ10 and B6 on immune response. 200 mg CoQ10 and 300 mg B6 were given separately or together to 3 groups, ages 30 to 75. The B6-only group had significant increases in T4 helper cells, no change in T8 levels, and a significant increase in the T4:T8 ratio. This represented an increase in cell-mediated immunity. (43)
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. (44) 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 (42). Depletion of B6 in humans decreases antibody production and reduces blood lymphocyte levels. (42)
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. (44) A vegetarian diet, typically low in both cysteine and B6, can be expected to be anti-immune health at least through this pathway.
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. (45) And without ATP there is no life. (45) 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. (46) 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. (44)
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." (47)
Mouse macrophage activity was measured in a 1983 study that compared CoQ10 and idebenone. Macrophages taken from control mice, CoQ10-treated mice, and idebenone treated mice were tested for cytolytic (killing), cytostatic (germ-growth inhibiting) and hydrogen peroxide activity. The cytolysis score was 0.9% for the control group, 6% for the CoQ10 group, and 24% for the idebenone group. The cytostasis score was 0 for the controls, 53% for the CoQ10 mice, and 92% for the idebenone mice. Hydrogen peroxide release was 37 for the controls, 360 for the CoQ10 mice, and 211 for the idebenone mice. Note that the higher hydrogen peroxide levels of the CoQ10 mice, lead to less germ killing/inhibition than the lower hydrogen peroxide levels of the idebenone mouse macrophages. This demonstrates the point made earlier that excessive phagocyte oxidant release often impairs germ killing/inhibiting activity. The researchers also reported that idebenone increased antibody-dependent cell cytotoxicity compared to controls, but CoQ10 did not. (48)
As mentioned in the B6 section, Folkers tested immune responses to CoQ10 with and without B6. The experimental results showed increased T4 helper cells, no change in T8 cells, and increased T4:T8 ratio in both CoQ10 and CoQ10/B6 subjects. (A seriously decreased T4:T8 ration is one of the main immunologic aberrations in AIDS). In addition, blood levels of the antibody IgG increased in the CoQ10 and CoQ10/B6 subjects. Folkers concluded that: "These increased in IgG and T-4 lymphocytes with CoQ10 and vitamin B6 are clinically important for trials on AIDS, other infectious diseases, and on cancer." (43)
A supplement of at least 100 mg CoQ10 and and/or 90 mg idebenone is a safe and useful immune booster. My own immune program includes both CoQ10 and idebenone.
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. (15) Bogden and colleagues reported that greater than 90% of healthy elderly subjects had zinc intake below the RDA. (9) Zinc deficiency is hardly a rare phenomenon.
Zinc is essential for the integrity of the thymus gland and for cell-mediated immunity. (3) The thymus incorporates zinc into the inactive form of thymulin, a thymic hormone, creating active thymulin (ZnFTS). (3) ZnFTS is necessary for the maturation and differentiation of stem cells into mature T cells. (6) T lymphocyte responsiveness to mitogens is increased by zinc. (6) 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. (6) An increase in natural killer cell activity also occurred.
Saha and colleagues reported that zinc supplementation of hydrocortisone-treated aged mice augmented T lymphocyte response to interleukins 1 and 2 and several different mitogens an average of 100%. (3) In this experiment zinc did better than injected ZnFTS in aiding T cell activation.
Hadden lists the following effects of dietary zinc deficiency on immune function: (Zinc may be properly considered one of the most critical immunonutrients):
Boukaiba and co-workers performed a 16 week crossover study with 44 institutionalized elderly adults, using 20 mg zinc/day. The subjects were divided into a lean and average weight group. The zinc supplementation led to a significant increase of active (zinc-bound) thymulin in the lean group, with a smaller increase in the active thymulin level in the average weight group. (9) This was a biologically important result as inactive thymulin increases with age, and inactive thymulin inhibits the activity of zinc-active thymulin. (6)
Extremely high zinc doses (300 mg/day) can be immunosuppressive (49), 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. (Ed. - Remember that our T1-Melatomin contains 50 mg zinc per tablet, as well as Melatonin and Selenium).
Re: Spikes in LH 
Linear Mode
