Immune System Strengthening

Antioxidants and Coenzyme Q10

Because of their ability to scavenge free radicals, antioxidants are important immune-system boosters. Supplementation with antioxidants like vitamins C and E and the B vitamins may improve immune function (Grimble RF 1997), and supplementation with vitamin A stimulates antibody-mediated immune responses (Cantorna M et al 1995).

Vitamin E is a powerful fat-soluble antioxidant. It protects cellular membranes of the immune system and other cells by trapping free radicals and enhances the effectiveness of lymphocytes (Kaminogawa S et al 2004).

Vitamin C (ascorbic acid) is a key component of the immune system and antioxidant defense (Kagan VE et al 1991; Kagan VE et al 1992; Peters E et al 1993). It prevents the production of free radicals and reduces DNA damage in immune cells. Moreover, vitamin C downregulates the production of pro-inflammatory cytokines and participates in recycling vitamin E (Schwager J et al 1998).

B vitamins indirectly contribute to antioxidant defenses and have considerable influence on immune function. Vitamins B12 and B6 are cofactors in the creation of cysteine, a key component in glutathione synthesis. Deficiencies in B vitamins and vitamin E create abnormalities in the immune response (Murrary R et al 2000).

Lipoic acid is a potent antioxidant with antiviral, free-radical-quenching, and immune-boosting qualities. It is unusual because it is soluble in both fat and water (Kagan VE et al 1992) and active in both its oxidized and reduced form (Bustamante J et al 1998). Lipoic acid is able to regenerate other antioxidants such as vitamins C and E and raise glutathione levels significantly (Packer L et al 1995; Packer L et al 1997; Scholich H et al 1989; Fuchs J et al 1993).

Coenzyme Q10 (CoQ10) is synthesized from the amino acid tyrosine. It is present in high quantities in the heart muscle and has shown a wide range of benefits. It is an essential cofactor in the production of adenosine triphosphate, which is the primary source of energy for all the body's cells. Levels of CoQ10 decline naturally as humans age, which may be related to increased lipid peroxidation. CoQ10 is a powerful antioxidant and scavenger of free radicals. It inhibits lipid peroxidation and works synergistically with vitamin E (Alleva R et al 1995). CoQ10 has an important role in the stimulation of the immune system and improves several parameters of immune function (Folkers K et al 1985).

Whey protein. Whey protein is isolated from milk. The proteins in whey are very available to the body, and whey protein contains potent antioxidants. Its antioxidant activity is due to its high concentrations of glutamate and cysteine, which are precursors to glutathione (Walzem RL et al 2002). Whey also contains several substances that enhance the immune system, including the following:

• Beta-lactoglobulin, which modulates lymphatic responses (Guimont C et al 1997)
• Alpha-lactalbumin, which has a direct effect on B and T lymphocytes and has the ability to reduce oxidative stress
• Lactoperoxidase, which reduces toxic hydrogen peroxide (Sundberg J et al 1991; Ha E et al 2003)

Lactoferrin, a major component of whey protein, also acts as an antioxidant (Steijns JM et al 2000) and can inhibit the absorption of bacteria through the intestinal wall. Whey protein can activate natural killer cells (Nishiya K et al 1982). In the laboratory, lactoferrin inhibited metastasis of cancer cells in mice (Marshall K 2004) and increased IL-2 and natural killer activity (Watanabe A et al 2000).

Minerals

Metallic micronutrients such as copper, zinc (Prasad AS 2000), and selenium influence the activity of antioxidant enzymes and can reduce oxidative stress. Among children, deficiencies of zinc, copper, and selenium have been linked to immune deficiency and infection (Cunningham-Rundles S et al 2005).

Selenium is involved in several key metabolic pathways (Rotruck JT et al 1973; McKenzie RC et al 1998; McKenzie RC 2000). Glutathione peroxidase, the enzyme that recycles glutathione, depends on the presence of selenium for its antioxidant activity (Arthur JR 2003). Plant food is a major dietary source of selenium—for example, garlic is rich in selenium—while the highest concentration of dietary selenium occurs in meat.

Zinc deficiency is linked to impaired immune function, partly because of decreased T lymphocyte and B lymphocyte function. Zinc has shown the ability to decrease inflammation and the production of IL-2 (Tanaka S et al 2005). Copper and zinc together have been shown to stimulate internally produced antioxidants such as glutathione and superoxide dismutase (SOD) (Kuppusamy UR et al 2005).

For safety information on copper, zinc, and selenium, see Safety Caveats at the end of this chapter.

DHEA and Immune Function

Dehydroepiandrosterone, more commonly known as DHEA, is produced by the adrenal glands. DHEA has over 100 metabolites and is used by the body for estrogen and testosterone production.

Blood levels of DHEA rise until they peak in the third decade of life, then rapidly decline. Endocrinologists and anti-aging researchers have been focusing on this decrease in DHEA, which in turn produces a decline in other steroidal hormones.

Animal experiments suggest that DHEA has many biological effects, including anticancer, immune-enhancing, neurotrophic, and general anti-aging effects (Bovenberg SA et al 2005). A recently published review article of DHEA supplementation in men found convincing research showing positive effects of DHEA on the cardiovascular system, body composition, the skin, the central nervous system, sexual function, and the immune system (Saad F et al 2005).

On the cellular level, DHEA exerts its actions on peripheral target tissues either indirectly, following its conversion to androgens, estrogens, or both, or directly, as a steroid hormone (Perrini et al 2005). Lower DHEA levels are associated with decreased production of IL-2 and an increase in the presence of IL-6, which is a pro-inflammatory cytokine (Hammer F et al 2005). A study was performed on younger and older men to compare DHEA blood levels and peripheral blood mononuclear cells (PBMCs) in populations of varying ages. The results showed significant changes in sex steroid metabolism by human PBMCs with aging, which may represent a link to age-associated changes in the immune system (Hammer F et al 2005).

The immunomodulatory effects of DHEA in various autoimmune diseases have been studied. Relative reductions in DHEA have been noted in patients with rheumatoid arthritis, systemic lupus erythematosus, HIV and AIDS, sepsis, and trauma (Chen CC et al 2004).

Overall, DHEA blood levels have been used as diagnostic factors in evaluating immune senescence. Supplemental DHEA has been clinically valuable when used to restore youthful hormonal blood levels in aging, stressed, and immune-compromised individuals (Valenti G 2004).

One of DHEA's metabolites, 7-keto DHEA, has also been studied for its ability to support the immune system. A study at the Minnesota Applied Research Center and the Geriatric Research Education and Clinical Center in Minneapolis found that four weeks of 7-keto DHEA supplementation improved immune function in elderly men and women (Zenk JL 2004).

In this randomized, double-blind, placebo-controlled study, 22 women and 20 men over the age of 65 took either 100 mg of 7-keto twice daily or a placebo. Patients in the 7-keto group had a significant decrease in immune suppressor cells and a significant increase in immune helper cells. The 7-keto group also saw reductions in diastolic blood pressure and an increase in neutrophils, the first white blood cells to respond to infection.

Polyunsaturated Fatty Acids

Polyunsaturated fatty acids, such as the omega-3 fatty acids found in fish oil and flaxseed oil, have been studied for their anti-inflammatory action (Kaminogawa S et al 2004). Polyunsaturated fatty acid reduces the inflammatory response caused by TNF-alpha (Johnson J et al 1993; Pedersen BK et al 2000), discussed above.

Most people in the United States have an imbalance in the ratio of omega-3 fatty acids to omega-6 fatty acids because of diets high in animal fat and vegetable oils high in omega-6 (e.g., corn oil). This imbalance has been associated with inflammation (Calder PC 1997). The ratio can be improved by taking supplemental omega-3 fatty acids. Omega-3 fatty acids have also been shown to

• Counteract suppression of the cellular immune system (Pedersen BK et al 2000)
• Suppress TNF-alpha production and have an anti-inflammatory effect (Grimble RF et al 2002)

Probiotics

The gastrointestinal tract relies on live bacteria (microflora) to help support a robust immune response. These probiotic bacteria are important because they help prevent foreign bacteria and allergens from passing through the intestinal wall and are important to the overall health of the intestinal immune system (Marteau P et al 2001; Conway PL et al 1987; Robins-Brown R et al 1981). Probiotics are found in foods such as yogurt and kefir, which enhance the microflora in the gut by providing additional probiotic bacteria (Fuller R 1991; Isolauri E et al 2001). The most commonly used probiotic bacteria are lactobacillus and bifidobacterium, found in yogurts.

Probiotics also strengthen the intestinal immunological barrier. Lactobacillus stimulates natural immunity by improving phagocytic and natural killer immune cell activity (Kaminogawa S et al 2004).

Grape Seed Extract

Chemicals in grape seeds known as proanthocyanidins have potent antioxidant and immune-boosting properties (Ashraf-Khorassani M et al 2004; Bagchi D et al 1997; Bagchi D et al 1998). They increase the activity of internal antioxidants such as glutathione and SOD (Peng Q et al 2000).

The antioxidants in grape seed extract are twice as potent as vitamin E and four times as potent as vitamin C (Bagchi D et al 1997; Bagchi D et al 1998). In laboratory studies, proanthocyanidins increased the power of natural killer cells, enhanced the production of IL-2, and decreased production of IL-6 (Cheshier JE et al 1996).

Green Tea Extract

Green tea extract, which contains a class of compounds known as catechins, has become increasingly popular as scientists learn more about its antioxidant and free radical–scavenging abilities. One of the most potent catechins in green tea is epigallocatechin-3-gallate (Chen A et al 2002). Green tea extract is also rich in vitamins C and B (Hasegawa N et al 2002; Hasegawa R et al 1998).

Green tea has a positive influence on lipid metabolism and exerts anticancer effects. Green tea modulates the inflammatory processes and protects against DNA damage (Lin AM et al 1998). The catechins from green tea demonstrate considerable antioxidant activity (Chen A et al 2002) and are potent free radical scavengers (Zhong Z et al 2003; Jimenez-Lopez JM et al 2004).