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