Artikel over de rol van DHA / Omega3

Docosahexeanoic Acid in Cancer Prevention and Therapy: The Silver Bullet?

Gregory K. Ogilvie, DVM, Diplomate ACVIM (Specialties of Internal Medicine, Oncology) and Philippe Bougnoux, MD Angel Care Cancer Center, California Veterinary Specialists, 100 North Rancho Santa Fe Rd., Suite 133, San Marcos, CA (Ogilvie and Laboratoire Nutrition, Crossance et Cancer INSERM 0211, IFR 120, Université François Rabelais, Tours, France (Bougnoux)

 

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 in expenditures, cures for high grade cancers have remained elusive. Fortunately, new knowledge about new and older therapeutic agents such as the long chain fatty acid of the n-3 series, docosahexaenoic 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 Angel Care Cancer Center, California Veterinary Specialists (CVS), are being treated with DHA to enhance the effect of chemotherapy and radiation therapy as an adjuvant therapy to prevent cancer progression and metastasis. These same caring veterinarians have often asked:

• Should all cancer patients be treated with DHA?
• Should DHA be administered to cancer patients to enhance the efficacy of chemotherapy and radiation therapy?
• Should DHA be prescribed to reduce the toxicity of radiation therapy?
• Should antioxidants such as vitamin E be administered to cancer patients receiving DHA?
• Should they be taking DHA?

 

DHA AND CANCER PREVENTION BY DELAY

The use of fatty acids such as DHA at the CVS Angel Care Cancer Center is designed to enhance disease free interval, survival and quality of life after surgery by reducing the rate of cancer development or incidence. This concept, known as 'cancer prevention by delay,' (Lippman and Hong, 2002) has recently been recognized and is an important mechanism behind the successes of several therapeutic agents including:

Tamoxifen, which has been shown to significantly diminish the risk of human breast cancer;

Retinoids and interferon-alpha to reduce the risk of head and neck cancer in dogs, cats and people;

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. The value of DHA as an agent to delay the occurrence of cancer 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, our 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 prostate 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 NMU-induced 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-/pro-oxidant compounds. They found that dietary n-3 fatty acids in the form of fish oil that contains DHA 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. The data suggested that oxidized n-3 fatty acids have an inhibiting role on tumor growth and emphasize the importance of the interaction of anti-/pro-oxidant compounds with n-3 fatty acids. There is a growing body of data based on our work as well as work does 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 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 of cancer cells.

 

DHA AND CHEMOTHERAPY

Dietary lipids such as DHA have been suggested to modify the sensitivity of tumors to ROS-generating anticancer 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 DHA in the blood and improved disease free interval (Ogilvie et al, 2000). Another study using the same randomized study design was used to assess 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, lipoperoxidation 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 diet provided to mammary tumors bearing rats abolished the enhancing effect of DHA on tumor sensitivity to anthracyclines. (de Poncheville et al, 2000). In all studies performed 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 DHA, for the treatment of spontaneously occurring cancer in dogs with the intent to provide evidence for its use in randomized human clinical trials.

  

For references: http://www.cvsangelcare.com/html/ac_dha.htm