~Immune Enhancement, Part 2 - Trace Elements

TRACE ELEMENTS

It is now understood that trace elements are essential, not only for their direct antioxidant activity, but also for their role as cofactors for a number of antioxidant enzymes. Wound-healing and immune function are highly dependent on adequate levels of trace elements, as well as vitamin levels. Dietary supplements of (some) trace elements are crucial to compensate for mineral-depleted soils providing much of the food we eat. Trace elements are greatly affected by what are called heavy metals--typically aluminum, arsenic, cadmium, lead, and mercury. Zinc is particularly susceptible to the effects of cadmium, a ubiquitous heavy metal.

Chowdhury et al. (1987) showed that in mice relatively low levels of cadmium would decrease NK cell activity and that this could be reversed by zinc. This led Chowdhury et al. to state: "Human civilization and a concomitant increase in industrial activity has gradually redistributed many toxic metals from the earth's crust to the environment and increased the possibility of human exposure. Among the various toxic elements, heavy metals cadmium, lead, and mercury are especially prevalent in nature due to their high industrial use. These metals serve no biological function and their presence in tissues reflects contact of the organism with its environment. They are cumulative poison." Heavy metals are basically poisonous to enzyme systems overall and should be removed from the body if present in excess by chelation or detoxification. Trying to overpower the action of heavy metals by taking extra nutrients to antagonize them is not advised (see Heavy Metal Toxicity protocol).

Zinc. The trace element zinc has many roles in basic cellular function. These include DNA replication, RNA transcription, cell division, and cell activation. Zinc is a specific activator of T-cells, T-cell division, and other immune cells (Prasad et al. 1997). Zinc also functions as an antioxidant and stabilizes membranes. Zinc-deficient patients display reduced resistance to infection, and Scott et al. (2000) found that in the parasite-infected host (in this case mice), any zinc deficiency results in better survival of the parasite. Thus, zinc is known to play a pivotal role in the efficiency of the entire immune system. In our diet, zinc and protein are linked, so that protein deficiency of any kind will inevitably result in zinc deficiency. Zinc is present in high-protein foods such as meat, oysters, nuts, and seeds. Zinc's importance in many aspects of the immune system, from skin barrier to lymphocyte gene regulation, may be based on its importance in cellular function.

Immune dysfunction and susceptibility to infection have been observed in zinc-deficient human subjects. A study investigated the production of cytokines and characterized the T-cell subpopulations in three groups of mildly zinc-deficient subjects (Prasad 2000). These included head and neck cancer patients, healthy volunteers found to have a dietary deficiency of zinc, and healthy volunteers in whom a zinc deficiency was induced by dietary means.

Prasad (2000) demonstrated that zinc status affects cytokine levels, but has no effect on the anti-inflammatory cytokines. Production of interleukin-2 and gamma-interferon was decreased even when the zinc deficiency was mild. Natural killer cell activity was also decreased in zinc-deficient subjects. T-cell formation was decreased even in mildly zinc-deficient subjects. The study demonstrates the crucial role of zinc in promoting specific immune responses.

Zinc is not only seen to be an important regulator of immunity but has also been found clinically to be an excellent mineral to take in the event of viral illness, such as the common cold. There have been contradictory studies in this regard, but a double-blind placebo-controlled trial published by Prasad (2000) was positive. It showed a very significant reduction in overall duration of cold symptoms (50%), cough (50%), and nasal discharge (30%) at a dose of 12.8 mg of zinc in a lozenge taken every 2-3 hours while awake. However, pro-inflammatory cytokine levels did not change significantly in this study. Zinc must be taken as a lozenge at the start of the cold symptoms to be effective.

Copper, Manganese, and Selenium. In addition to zinc, copper, manganese, and selenium act as cofactors of antioxidant enzymes to protect against oxygen free radicals produced during oxidative stress (Leung 1998). Although all are essential, selenium is found to be most deficient in traumatized patients. In recent years, the benefits of selenium have been recognized by researchers as an effective protector against certain cancers, such as breast, lung, liver, urogenital, colorectal, prostate, and ovarian cancer, by removing harmful lipids and hydroperoxides from the body. In addition to being a regulator of enzyme reactions, selenium acts with vitamin E, and the two are intricately interwoven as antioxidants in the glutathione regeneration cycle. Cell-mediated immunity is impaired by this pair's deficiency.

A copper deficiency will impair lymphocyte response to antigen stimulants and also impairs cell-mediated immunity. Copper is an important cofactor in many of the body's enzyme reactions, including the antioxidant splitting enzyme superoxide dismutase, and again may be deficient in our diet. Once again, however, an excess of this nutrient may be toxic.

Manganese is also involved in many antioxidant functions, but it has been found in levels that are too high in some patients on home parenteral nutrition. It is also involved in the generation of glutathione, an important antioxidant.

A convenient way of obtaining most of the nutrients needed for healthy immune function is to take 3 tablets 3 times daily of the 89-ingredient Life Extension Mix. One capsule daily of Life Extension Booster provides additional amounts of the nutrients that protect immune system cells against damaging free radicals.

A number of studies have shown that the combination of zinc and selenium enhances immunity in the elderly. A pioneering study published in the Lancet (Chandra 1992) found that seniors taking modest doses of a multivitamin/multimineral supplement containing zinc and selenium showed a general reduction in infection and required antibiotics for significantly fewer days annually. A more recent study brings the effect of these two minerals into sharper focus. This well-designed study (randomized, placebo-controlled, double-blind) found that seniors taking zinc and selenium had significantly fewer infections over a 2-year period, but that vitamin supplementation alone did not have a major effect (Girodon et al. 1997). The zinc and selenium supplement cut the number of infections by nearly two-thirds compared to placebo. A follow-up study demonstrates that seniors supplemented with zinc and selenium show improved antibody response to the flu vaccine (Girodon et al. 1999).

PROBIOTICS

Probiotics are natural substances that can be taken by humans to enhance the bacterial flora of the intestinal tract. The better-known probiotic is Lactobacillus acidophilus that is found in live yogurt cultures and can be helpful in combating yeast and other organisms that should not be in the GI tract. Arunachalam et al. (2000) have found Bifidobacterium lactis (1.5 1011 units) in low-lactose milk consumption by healthy elderly subjects improves immune function after 6 weeks as measured by enhanced levels of alpha-interferon and phagocytic cell capacity. In one animal study, Perdigon et al. (1988) showed a strong response to L. acidophilus, L. bulgaricus, and L. casei via the oral route. In general, probiotics are known for their ability to create a positive environment in the human GI tract for enhanced immunity, appropriate gut flora balance, and enhanced nutrient formation for enterocytes (cells of the intestinal wall) (Chiang et al. 2000; Gill et al. 2001a; 2001b).

Lactoferrin. Lactoferrin can be considered a prebiotic, that is, a substance that when ingested suppresses the formation of antagonistic bacteria, thereby promoting the production of probiotics, such as acidophilus. Will Brink (2000) wrote an article in Life Extension Magazine on lactoferrin that reviews the literature on this substance, which is a fraction of whey protein. Although many of the studies are on animals, lactoferrin is present naturally in many mucous membrane secretions in the human, suggesting an innate human immune enhancing function (Nishiya et al. 1982). Brink suggests that the apo-form of lactoferrin is the best. It appears to act partially by increasing the production of probiotics, such as L. acidophilus, and, at least in animal studies, inhibits pathogenic bacterial growth, such as Escherichia coli, Staphylococci, and Helicobacter pylori (Wada et al. 1999).

FATS

The kind of fat that we eat will determine the balance of proinflammatory and anti-inflammatory hormones and messengers. In addition, the structure of all our cells will be determined by the amounts of saturated versus unsaturated fat in our diet. The omega-3 series dietary fatty acids (polyunsaturated or PUFAs) are rapidly incorporated into cell membranes, and profoundly influence biological responses. These lipids influence membrane stability, membrane fluidity, cell mobility, the formation of receptors, binding of ligands to their receptors, activation of intracellular signaling pathways either directly or through the formation of eicosanoids, gene expression, and cell differentiation. For the most part, in the Western world we are oversupplied with saturated fats that lead to the expression of inflammatory messengers, rigid cell walls, and fatty deposits in the arteries.

In terms of immune system function, most studies show that dietary intake of linoleic acid (LA) has a strong growth-promoting effect on many rodent tumors, whereas fatty acids, such as alpha-linolenic and eicosapentaenoic acids (EPAs) are recognized as cancer chemo-preventive (Penturf et al. 1997). However, Sauer et al. (2001), writing on the mechanism for the antitumor and anticachectic effects of n-3 fatty acids, stated: "In general, eicosanoids [prostaglandins] formed from the omega-3 fatty acids are much less potent in causing biological responses than those formed from the omega-6 fatty acids, including stimulation of cytokine production and inflammatory responses. In well-controlled clinical studies, consumption of omega-3 fatty acids has resulted in reduction of cardiovascular diseases including arrhythmias and hypertension, protection from renal disease, improvement in rheumatoid arthritis, improvement in inflammatory bowel diseases, reduced episodes of rejection, and protection from infection."

Teasing out the different effects of fats on the immune system is in a state of transition, no doubt due to the widely differing effects that different fats can have on different cells, and on the membrane structure of all cells.

OTHER FACTORS

Other factors that influence immunity are manifold. Chandra et al. (1991) have identified multiple factors that can predispose to immune dysfunction in the elderly--living alone, physical or mental disability, recent loss of spouse or significant other, use of multiple medications, poverty, and high alcohol consumption. The emotional and social factors should not be taken lightly. We have already discussed the impact of GI integrity and thinning of the bowel wall as a significant factor in immune response.

Continued . . .


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