Special Care Foundation founder Dr. Gregory K. Ogilvie has been an integral part of confirming research on the healing properties of docosahexaenoic acid. DHA or docosahexaenoic acid is an omega-3 fatty acid. Most commonly expressed from salmon and other cold water fatty fish, recent research indicates that deep ocean algae maybe a more potent source. Algae based DHA is usually absent of the toxins sometimes found in the cold water fish that feed on it.
The latest cancer research, which includes that done through the Special Care Foundation, has found that DHA significantly impacts cancer patients by reducing its ability to grow or spread.
Since our bodies only produce small amounts of DHA, we must get the amounts we need from our diet and supplements. Most people in the Western world do not get enough DHA in their daily diet. Women, men, cats, and dogs with cancer can all benefit from quality sources of DHA.
Cancer is a major cause of morbidity and mortality in dogs, cats and women worldwide.The ultimate goal for the treatment of malignancies is to eliminate all evidence of cancer resulting in a cure. With high-grade malignancies, this is usually accomplished with a combination of surgery, chemotherapy, radiation, and more recently, molecular approaches of cancer therapy. Despite decades of intense effort and billions of dollars of expenditure, cures for high-grade cancers have remained challenging. Fortunately, new knowledge about new and older therapeutic agents such as the long chain fatty acid of the n-3 series, docosahexaenic acid (DHA), has resulted in improved quality and quantity of life.
Many referring veterinarians in San Diego County have noted that the medical, surgical and radiation oncologists associated with California Veterinary Specialists (CVS)Angel Care Cancer Center are using DHA to enhance the effect of chemotherapy and radiation therapy as an adjuvant therapy to prevent cancer progression and spread of cancer throughout the patient’s body. The information below supports the following hypothesis and conclusion:
• Many cancer patients can benefit from DHA supplementation. DHA should be algae based and not derived from fish oil due to the potential of heavy metal and organophosphates (a chemical used for killing insects and small animals that damage crop) contamination. Small dogs and cats should receive 200mg once daily, medium sized dogs should receive 200mg twice daily, large breed dogs should receive 200mg three times daily and giant breeds should receive 200mg four times daily.
• DHA should be administered to cancer patients to enhance the effectiveness of chemotherapy and radiation therapy.
• DHA should be prescribed to reduce the toxicity of radiation therapy.
• Antioxidants such as vitamin E and C should not be administered to cancer patients receiving DHA, radiation therapy and some chemotherapeutic agents as they will reduce response to therapy.
DHA AND CANCER PREVENTION BY DELAY
The use of fatty acids such as docosahexaehoic acid at the CVS Angel Care Cancer Center is designed to enhance disease free interval (time without any evidence of cancer), survival and quality of life after surgery by reducing the rate of cancer development or incidence. This concept, known as ‘cancer prevention by delay’ has recently been recognized and is an important mechanism behind the successes of several therapeutic agents including (Lippman and Hong, 2002):
• Tamoxifen that has been shown to significantly diminish the risk of human breast cancer,
• Retinoids and interferon-alpha to reduce the risk head and neck cancer in dogs, cats and people, and
• Nonsteroidal anti-inflammatory drugs to delay or reduce the development of colorectal cancer in human beings, transitional cell carcinomas in dogs and cats, and squamous cell carcinomas in dogs and possibly cats.
The delay of cancer growth and development, also known as clinical cancer chemoprevention, is a valuable clinical tool until permanent or absolute cancer prevention can be achieved. DHA is a valuable agent to delay the occurrence of cancer and can only be understood by exploring its value as a cancer chemopreventative and as an agent to enhance the effect of radiation and chemotherapy.
DHA AND CANCER: THE EVIDENCE
For the last decade, laboratories in France, Colorado and now at Angel Care Cancer Center in California have been involved in the search for dietary lipids associated with a delay in cancer relapse. Dietary lipids such as DHA appear to influence the growth of many types of cancer including breast and prostatic cancer. (Franceschi et al., 1995; Braga et al., 1997, Fay et al., 1997, Thompson et al., 1996). From a cohort of women treated for localized presentations of breast cancer, the group in France used adipose tissue sampled during surgery as a biomarker of past dietary intake of polyunsaturated fatty acids (Bougnoux et al., 1994). They found elevated n-3 fatty acids, especially DHA to be associated with a higher metastasis-free survival, suggesting that these fatty acids could potentially delay metastasis by decreasing tumor growth or development.
Furthermore, using a case control approach comparing the fatty acid composition of adipose breast tissue obtained at the time of the surgical removal of either malignant or benign breast tumors, the French group found both alpha linoleic acid and DHA to be positively associated with a decreased risk of having breast cancer (Maillard et al., 2002). They also explored the role of n-3 PUFA on mammary tumor growth using the experimental system of mammary tumors in rats Because fatty acids are substrates for lipid peroxidation processes, the group in France studied the effects of n-3 fatty acids on tumor growth in interaction with anti- or pro-oxidant compounds. They found that dietary n-3 fatty acids in the form of fish oil that contain docosahexaenoic acid inhibited tumor development. Furthermore, this tumor growth inhibition was most evident in the absence of the antioxidant vitamin E. Inhibition of tumor growth was even greater when the n-3 fatty acids were given in the presence of pro-oxidants (Cognault et al., 2000). Such effects were not found when the lipid diet was low in fatty acids. These data suggested that oxidized n-3 fatty acids have an inhibiting role on tumor growth and emphasize the importance of the interaction of anti- and pro-oxidant compounds with n-3 fatty acids. There is a growing body of data based on our work as well as work done by others that suggests the effect of n-3 fatty acids such as DHA seem to involve several steps of tumor formation. N-3 fatty acids such as DHA:
i. Inhibit tumor vessel formation (angiogenesis)
ii. Inhibit cell proliferation in several epithelial cell lines.
iii. Enhance the rate of tumor cell death
iv. Induce lipid peroxidation (process whereby free radicals steel electrons from the lipids in cell membranes, resulting in cell damage and increased production of free radical) which enhances the efficacy of radiation and chemotherapy induced cancer cell death; this effect is diminished or reduced dramatically with vitamin E.
v. Suppress the expression of cyclooxygenase-2 in tumors therefore decreasing cancer cell proliferation.
vi. Suppression of NF kappa B activation and bcl-2 expression thus allowing apoptosis (a process causing cancer cell death) of cancer cells
DHA AND CHEMOTHERAPY
Dietary lipids such as DHA have been suggested to modify the sensitivity of tumors to ROS-generatinganticancer drugs which is the reason it is incorporated into the treatment regimen of some patients at Angel Care Cancer Center. For example, when dogs with lymphoma were treated with doxorubicin chemotherapy and a diet supplemented with n-3 fatty acids in the form of fish oils, there was a direct correlation between the level of docosahexaenoic acid in the blood and improved disease free interval (Ogilvie et al, 2000). Another study using the same randomized study design was used to assess at the efficacy of n-3 fatty acids in combination with doxorubicin chemotherapy to improve the disease free interval in dogs with hemangiosarcoma, a highly metastatic, rapidly fatal malignancy. There was a statistically significant positive correlation between the n-3 fatty acids and disease free interval (Richardson et al, In press). A similar approach was used in rats bearing autochthonous, NMU-induced mammary tumors. We found that dietary supplementation with fish oil or DHA increased the sensitivity of mammary tumors to anthracyclines, compared with dietary supplementation with saturated fatty acids (de Poncheville et al., 2000). Since DHA is the most polyunsaturated of the polyunsaturated fatty acids, lipoperoxydation is suspected to be a likely molecular mechanism implied in the enhancement of the response of the cancer cells to cytotoxic drugs. Addition of vitamin E to the diet provided to mammary tumor bearing rats abolished the enhancing effect of DHA on tumor sensitivity to anthracyclines. (de Poncheville et al, 2000). In all studies done to date, there has been no clinically significant toxicity other than transient gastrointestinal distress linked to the dietary change (Ogilvie et al, 2000, McNiel et al, 1999, Swaim et al, 1989). Therefore, based on the safety and efficacy profile of n-3 fatty acids, it seems reasonable to further define the efficacy of n-3 fatty acids, especially docosahexaenoic acid for the treatment of spontaneously occurring cancer in dogs with the intent to provide evidence for its use in randomized human clinical trials.
DHA AND RADIATION THERAPY
Radiation therapy is currently the most effective treatment for many localized malignancies including those within the nasal cavity. Research is underway at Angel Care Cancer Center to identify methods to maximize efficacy of radiation while minimizing the adverse effects associated with radiation therapy. Among the agents being evaluated to minimize the normal tissue damage are long chain polyunsaturated fatty acids of the n-3 series such as docosahexaenoic acid and eicosapentaenoic acid, which readily are incorporated into cell membranes and ameliorate inflammation and carbohydrate dyshomeostasis. In a study involving 12 dogs with histologically confirmed malignant carcinomas of the nasal cavity, dogs were randomized to receive isocaloric amounts of a diet supplemented with menhaden fish oil including DHA (experimental diet) or an otherwise identical diet supplemented with corn oil (control diet). Megavoltage radiation was delivered to all dogs. The data in that study suggested that feeding a diet supplemented with fish oil and arginine is associated less toxicity and enhanced quality of life in dogs with nasal cancer.
Tumor sensitisation to radiation by polyunsaturated fatty acids has been investigated. Vartak et al. (1997) (1998) studied the in vitro response of a chemically-induced rat malignant astrocytoma cell line to radiation after the cell culture medium was supplemented with gamma-linoleic acid (GLA) or long chain n-3 PUFA (EPA or DHA), and found that n-3 PUFAs enhanced radiation-induced cell cytotoxicity. Colas et al (2003) documented enhanced radiosensitivity of rat autochthonous mammary tumors by dietary docosahexaenoic acid.
Whether dietary n-3 fatty acids can lead to enhanced sensitivity of tumor tissue in the absence of a similar increase in the radiosensitivity of non-tumor tissue remains a critical issue. Several studies have suggested that PUFAs do not sensitize normal tissues to radiation. For example, since ionizing radiation generate ROS, we initiated a study to determine whether dietary DHA might sensitize mammary tumors to irradiation using a model where mammary tumors were induced by N-methylnitrosourea (NMU) in Sprague-Dawley rats. In the study, we showed that dietary DHA sensitized mammary tumors to radiation. The addition of vitamin E inhibited the beneficial effect of DHA, suggesting that this effect might be mediated by oxidative damage to the peroxidizable lipids (Colas et al, 2003).
Appel, MJ, Van Garderen-Hoetmer, AM. and Woutersen, RA. Effects of dietary conjugated linoleic acid on pancreatic carcinogenesis in rats and hamsters. Cancer Res 54, 2113-2120, 1994.
Aro A, Mannisto S, Salminen I, Ovaskainen ML, Kataja V, Uusitupa M. Inverse association between dietary and serum conjugated linoleic acid and risk of breast cancer in postmenopausal women. Nutr Cancer 2000;38(2):151-7
Banni, S and Martin, JC. Conjugated linoleic acid and metabolites. In: Trans fatty acids in human nutrition,. JL. Sébédio (ed.), Dundee: The oily press, 1998, pp. 261-302.
Bougnoux, P. (1999) n-3 polyunsaturated fatty acids and cancer. Curr. Opin. Clin. Nutr. Metab. Care, 2, 121–126
Bougnoux, P., Koscielny, S., Chajes, V., Descamps, P., Couet, C. & Calais, G. (1994) Alpha-linolenic acid content of adipose breast tissue: a host determinant of the risk of early metastasis in breast cancer. Br. J. Cancer, 70, 330–334