Although the direct effect of nutritional supplements on the effectiveness of cancer immunotherapy has yet to be clinically evaluated, the impact of nutrition, particularly micronutrients, on immune cell function (that is, immunonutrition) is central to the success of any cancer treatment (Calder PC et al 2002b; Chandra RK 1999). Several nutrients are able to modulate immune response and counteract inflammatory processes. Zinc, omega-3 fatty acids, and glutamine all act differently to modulate immune response, but all appear to have the potential to protect against cancer progression (Grimble RF 2001).
Immunonutrition has gained recognition as an adjuvant cancer therapy and should be an integral part of cancer immunotherapy, particularly against cancers associated with chronic inflammation (Philpott M et al 2004), as it has beneficial effects on patient outcomes, enhances the immune response, and improves the prognosis of cancer patients (Chermesh I et al 2004).
Cells of the immune system that are essential for the success of cancer vaccines include:
- Dendritic cells
- CD4 T cells (lymphocytes)
- CD8 T cells (lymphocytes)
- B cells (lymphocytes)
- Natural killer (NK) cells
Micronutrients that have been established as being essential to the optimal function of these immune cells include zinc, vitamins C and E, folic acid, and glutamine (Calder PC et al 1999; Calder PC et al 2002b).
Zinc. Zinc supplements improve immune cell function (Ibs KH et al 2003; Prasad AS et al 2002). Indeed, diets lacking in zinc are linked to reduced CD4 and CD8 T-cell function (Chandra RK 1999). While deficiencies in zinc also compromise the function of natural killer cells, macrophages, and neutrophils (Ibs KH et al 2003), this impairment of the immune system can be reversed by dietary zinc supplements (Chandra RK 1999; Ibs KH et al 2003). Zinc supplements should, however, be carefully monitored, as excessive intake (over 100 mg per day) is counterproductive and reverses any benefits seen with the suggested doses of 20 to 50 mg per day (Calder PC et al 2002b; Hercberg S et al 1998; Kohn S et al 2000).
Zinc supplements of 50 mg a day improve the structure of Langerhans’ cells (a type of dendritic cell found in the skin epidermis) by endowing them with a more dendritic (or finger-like) structure that improves their mobility and thus their ability to pick up antigens and transport them to lymphocytes (Kohn S et al 2000).
Astragalus. Astragalus, an herb used for centuries in Asia, has exhibited immune-stimulatory effects. Astragalus potentiates lymphokine-activated killer cells (Chu 1988). One study found that astragalus could partially restore depressed immune function in tumor-bearing mice (Cho 2007a), while another concluded that “…astragalus could exhibit anti-tumor effects, which might be achieved through activating the…anti-tumor immune mechanism of the host” (Cho 2007b).
Antioxidants (Vitamins C and E). Supplementing the diet of colorectal cancer patients with high doses of vitamin E (750 mg per day) for two weeks increased lymphocyte numbers and improved the lymphocytes’ ability to produce messengers (interleukin-2 and interferon gamma) that are associated with the type of immune response required to destroy cancer cells (Malmberg KJ et al 2002). Therefore, high-dose vitamin E supplements may be considered to support the use of cancer vaccines and immunotherapy. Long-term supplementation at lower doses of 100 to 200 mg a day has improved immune function (Calder PC et al 2002b; Pallast EG et al 1999).
Vitamin C supplements also improve immune function and protect lymphocytes against damage (Lenton KJ et al 2003; Schneider M et al 2001).
Folic Acid. Deficiencies in folic acid impair the immune system by reducing the ability of CD8 T cells to divide and increase in number (Courtemanche C et al 2004). In addition, low levels of folic acid lead to genetic instability in lymphocytes and increased cell death, or apoptosis (Courtemanche C et al 2004; Duthie SJ et al 1998). However, the impairment of lymphocyte function can be restored by folic acid supplements (Courtemanche C et al 2004).
Vitamin B12. Vitamin B12 plays a key role in immune function, as B12 deficiencies in humans lead to low numbers of CD8 T cells and impair the activity of natural killer cells (Tamura J et al 1999). These cells are essential for the cytotoxic arm of the immune system, which in turn is essential for destroying cancer cells. Supplementing with B12 restores CD8 T-cell numbers and natural killer cell activity (Tamura J et al 1999).
Vitamin B6. Deficiencies in vitamin B6 impair the immune system and are associated with a reduced ability of lymphocytes to produce messengers (cytokines) required for sustained immune activation (Doke S et al 1998).
Selenium. Selenium supplements (100 mcg a day) improve immune cell function by increasing the cells’ ability to produce messengers (cytokines) associated with the type of immune responses required to clear tumor cells (Broome CS et al 2004).
Glutamine. Glutamine supplements (30 grams a day) sustain immune cell function (Yoshida S et al 1998). Clinical studies have shown glutamine supplements to be particularly effective in counteracting immunosuppression associated with surgery (Calder PC et al 1999; O'Riordain MG et al 1996), and thus to be of benefit to patients undergoing an immunotherapy/vaccination regimen after surgical removal of the tumor.
Ginseng. The medicinal herb ginseng improves immune cell function (Larsen MW et al 2004). Of particular importance to the successful use of cancer vaccines is the recently reported ability of ginseng products to drive the development of dendritic cells that are essential for successful cancer vaccination (Takei M et al 2004).
Melatonin. Melatonin hormone supplements (20 mg a day, at bedtime) improve lymphocyte function and have been tested in clinical studies of blood cancers (El-Sokkary GH et al 2003; Lissoni P et al 2000).
Garlic. Garlic extracts boost the activity of natural killer cells against tumor cells (Hassan ZM et al 2003).
Mushroom Extracts (AHCC). Extracts from various mushrooms boost immune cell function (Kidd PM 2000). In particular, active hexose correlated compound (AHCC) improves the function of natural killer cells and confers benefits to liver cancer patients after surgical removal of the tumor (Matsui Y et al 2002).
PSK. PSK, which is a specially prepared polysaccharide extract from the mushroom Coriolus versicolor, has been studied extensively in Japan where it is used as a non-specific biological response modifier to enhance the immune system in cancer patients (Koda 2003; Noguchi 1995; Yokoe 1997). PSK suppresses tumor cell invasiveness by down-regulating several invasion-related factors (Zhang 2000). PSK has been shown to enhance NK cell activity in multiple studies (Ohwada 2006; Fisher 2002; Garcia-Lora 2001; Pedrinaci 1999).
Reishi. The active constituents of Reishi mushroom include polysaccharides, a unique protein named LZ-8, and triterpenes (Bao 2001; Xu 2011; Yeh 2010). Among its broad-spectrum immune-boosting effects are the following:
- Reishi promotes specialization of dendritic cells and macrophages, which are essential in allowing the body to react to new threats, vaccines, and cancer cells (Cao 2002; Lai 2010; Jan 2011; Ji 2011; Chan 2005).
- Reishi’s effects on dendritic cells have been proven to boost the response to tetanus vaccine; the mushroom’s proteins are also under investigation as “adjuvants” to emerging cancer DNA vaccines and other immune-based cancer treatments (Lai 2010; Chu 2011; Lin 2011; Zhu 2012).
- Reishi polysaccharide triggers growth and development of bone marrow, where most immune cells are born; following bone marrow eradication by chemotherapy, Reishi increased production of both red and white blood cells (Zhu 2007). Reishi polysaccharides provide immune-boosting function to circulating cancer-killing white blood cells of various types (Xu 2011).
- Reishi increases numbers and functions of virtually all cell lines in the immune system, such as natural killer cells, antibody-producing B cells, and the T cells responsible for rapid response to a new or “remembered” antigen (Jan 2011; Wang 2012; Jeurink 2008).
Laboratory and animal studies confirm that Reishi stimulates an appropriate anticancer immune response while quashing a cancer-promoting inflammatory one. A few small human studies have demonstrated Reishi's ability to enhance immune function in patients with advanced cancers (Wang 1997; Ooi 2000; Gao 2003).
Omega-3 Fatty Acids. The ratio of omega-3 and omega-6 polyunsaturated fatty acids (PUFA) modulates the inflammatory response. Inflammatory cells typically contain high levels of arachidonic acid and low levels of omega-3 PUFA (Calder PC 2002, 2002a). Increasing omega-3 fatty acid intake antagonizes arachidonic acid levels in inflammatory cell membranes, and decreases the amount of arachidonic acid that is available for production of pro-inflammatory arachidonic acid-derived mediators (Calder PC 2003).
Omega-3 PUFA may have indirect immunomodulatory activity mediated through tumor necrosis factor-alpha (TNF-a) and nuclear factor-kappa beta (NF-?B) production (Babcock TA et al 2002). Administration of omega-3 fatty acids before and after surgery (prior to immunotherapy) may have a favorable effect on outcome by lowering the magnitude of inflammatory response and preventing immune suppression (Weiss G et al 2002). Fatty fish such as salmon, mackerel, tuna, and herring are good sources of long-chain omega-3 PUFA.