A diet high in polyunsaturated fatty acids, especially omega 3s, have been shown to be negatively associated with cancer development

 Dietary fatty acids have been recognized as influential factors in the activation of carcinogenic events or disease progression and have been associated with a direct connection to breast cancer prevention.

PUFAs differentially inhibit mammary tumor development by inflicting modifications to the morphology of cell membranes, and influencing signaling pathways, gene expression and apoptosis.

The human body is unable to synthesize long-chain polyunsaturated fatty acids (PUFAs) Omega 3 DHA, docosahexaenoic, and EPA, Eicosapentaenoic acid and Omega 6 Arachidonic Acid at a reasonable rate and therefore, supplementation is required through dietary sources or nutritional supplements. The recommended daily nutritional dose is 2,000 mg EPA+DHA, while therapeutic dosing is 4,000-6,000 milligrams of EPA+DHA per day.

 Omega Three Fatty Acids and the Tumor Microenvironment

1. Supports Normal Inflammation Control by lowering COX 2, LOX5, PGE2, IL1, IL6,TNFa, CRP.
   • Increased inflammation contributes to cancer development, progression and metastasis.
   • Increased inflammation is linked to cancer related pain, fatigue, depression and cognitive impairment.
   • Increased inflammation is linked to cancer related hypercoagulation and risk of thromboembolism
   • Supporting Normal Inflammation control has a wide impact on the behavior of tumor cells and on safety and quality of life for cancer patients and survivors.
2. Promotes Expression of M1 Type Tumor Associated Macrophages (TAMs).
   • Type M1 TAMs promote tumor regression, inflammation control and immune activation by promoting tumor infiltration by antigen presenting dendritic cells and cytotoxic T cells.
3. Inhibits VEGF (Vascular Endothelial Growth Factor) and Promotes Normal Control of Angiogenesis .
   • VEGF promotes the development of new blood vessels to the tumor cells. Inhibition of VEGF and the development of capillaries inhibits tumor growth and profession as well as metastasis.
      
4. Down regulates tumor promoter Protein Kinase C isoenzymes,
   • A group of enzymes that link multiple cellular processes responsible for regulation of tumorigenesis, cell cycle progression and metastasis.
5. Inhibits Collagenase,
   • A proteolytic enzyme that breaks down the ECM (Extracellular Matrix) and allows invasion of tumor cells into tissues and blood vessels, leading to progression, invasion and metastasis.
6. Promotes Normal Apoptosis signaling.
   • Cancer cells lose the ability to initiate apoptosis, the normal process in which a cell recognizes itself as aberrant and self destructs. The inhibition of normal apoptotic signaling in malignant cells is a hallmark  of the tumor microenvironment permissive of uncontrolled growth, persistence and immortality due to loss of normal regulation.
7. Lowers Bcl2 and Ras oncogenes.
   • These genes inhibit normal apoptosis and promote tumor growth and progression.
8. Acts as a Chemo-sensitizer
   • Working synergistically to enhance therapeutic effect of chemotherapy drugs. DHA has a potential to specifically chemo-sensitize tumors.
   • Tumour cells can be made more sensitive to chemotherapy than non-tumor cell when membrane lipids are enriched with DHA
   • Incorporating DHA during treatment reduces adverse effects of chemotherapy.
   • DHA can improve the outcome of chemotherapy when highly incorporated into cell membranes.
9. Acts as a Radio-sensitizer.
   • By promoting normal membrane structure and function and by influencing the tumor microenvironment DHA acts synergistically to potentiate therapeutic effects of radiotherapy on tumor cells.
10. Promotes Healthy 16-OH Estrogen metabolism.
    • Estrogen can be metabolized through multiple pathways. The promotion of 16-Hydroxylation of estrogen produces estrogen metabolites that are not pro-carcinogenic. Omega 3 Fatty Acids promote healthy estrogen metabolism.
11. Inhibits Platelet Aggregation and Thrombin Formation.
    • Abnormal hyper-coagulation, increased platelet aggregation and thrombus formation are hallmarks of the tumor microenvironment. Control of platelet aggregation and thrombus formation reduces the risk of life threatening and adverse  thrombotic events.  40% of all cancer patients are at risk for the formation of thromboembolisms.  Omega 3 Fatty Acids reduce this risk.
12. Promotes Normal Cell Membrane Functions and Receptor Binding
    • A healthy flexible cell membrane built of omega 3 fatty acids promotes an enhancement of all membrane functions, normalizing and optimizing normal and therapeutic physiology.
13. Increases expression of Tumor Suppressor Gene PTEN.
    • Increased expression of tumor suppressor genes leads to enhanced control over carcinogenesis,  tumorigenesis and metastatic progression.
14. Inhibits Multi Drug Resistance.
    • Tumor cells can quickly become resistant to therapeutic anti-neoplastic agents thus decreasing and shortening the efficacy of treatments.
15. Inhibits cachexia preserves muscle mass and bone mass (inhibits proteolysis inducing factor)
    • Loss of bone mass (osteopenia) and loss of muscle mass (sarcopenia) are risk factors of aging and of the cancer physiology.  Maintaining bone mass and muscle mass are crucial to robust healthy function and quality of life.
16. Supports normal mood regulation.
    • Depression and anxiety are common in cancer patients. Support of balanced mood allows cancer patients deep and restful sleep, improved quality of life and increased coping capacity and resilience in the face of stress.

Cautions and Contraindications

• Patient on anticoagulant medications
• Patients with thrombocytopenia and known hypo-coagultion clotting disorders
• Pre and Post Surgical patients (72 hours)
• Patients with seafood allergies

How to Measure Omega 3 Fatty Acid Status

Serum or Plasma Omega 3 Fatty Acid ratios. LABCORP Omega 3-6 Fatty Acids, Quest Diagnostics Omegacheck, Boston HeartLab Fatty Acid Balance, Cleveland HeartLab Omegacheck, Genova Diagnostics Essential and Metabolic Fatty Acids, Great Plains Comprehensive Fatty Acids, OmegaQuant Omega3 Index.

Selected References

 Azrad M, Turgeon C, Demark-Wahnefried W. Current evidence linking polyunsaturated Fatty acids with cancer risk and progression. Front Oncol. (2013) 3:224.

 Bartsch H, Nair J, Owen RW. Dietary polyunsaturated fatty acids and cancers of the breast and colorectum: emerging evidence for their role as risk modifiers. Carcinogenesis. (1999) 20:2209–18.

 Bournoux, P. Et al. Improving outcome of chemotherapy of metastatic breast cancer by DHA: Phase II Trial, Br.J Cancer 2009 Dec 15:101(12):1978-85

 Shweta Tiwary   Altered Lipid Tumor Environment and Its Potential Effects on NKT Cell Function and Tumor Immunity.  Front Immunol.10.3389/fimmu.2019.02187

 Zanoaga O, Jurj A, Raduly L, Cojocneanu-Petric R, Fuentes-Mattei E, Wu O, et al. Implications of dietary omega-3 and omega-6 polyunsaturated fatty acids in breast cancer.  Exp Ther Med. (2018) 15:1167–76. 10.3892/etm.2017.5515