Effects of An Omega 3 Fatty Acid Supplement Consumption On Platelet Aggregation Tests in Patients Low Grade Lymphoproliferative Disorders.

Omega 3 fatty acids, when supplemented to cell culture or in the diet of tumor bearing animals, have been shown to sensitize mouse leukemias and lymphomas or multiple human solid tumor types to chemotherapy drugs. Enhanced chemosensitivity has been associated with suppression of nuclear factor kappa B (NFkB) activation and increased susceptibility to lipid peroxidation. Some investigators have expressed concerns over a possible bleeding diathesis related to the chronic consumption of these supplements.

We have initiated a pilot study in patients with low grade lymphoproliferative disorders to determine omega 3 fatty acids supplements tolerance; correlation of oral supplementation with incorporation of omega 3 fatty acids in blood cell membranes and in-vitro sensitivity of leukemia cells to chemotherapy. Omega 3 capsules, containing 1250 mg total oil, 60% of which is omega 3 were administered 3 times daily. Doses were escalated after the first month to 6 capsules per day and to 9 capsules after the second month, if there was good tolerance. As part of safety monitoring, platelet aggregation studies were done at base line and at 6 months, utilizing a Siemens Dade PFA-100 analyzer. Fatty acid composition of red blood cells was assessed using gas chromatography.

Eight patients with Chronic Lymphocytic Leukemia (Rai stage 0-1, no requiring therapy) have been accrued to date. Six of the 8 patients were also receiving aspirin at the time of study. A dose-related increase in the omega 3 fatty acid content of both red blood cells and leukocytes was documented. The total omega 3 content of red cells was about 80% over base line after 3 capsules per day for one month; after 6 capsules per day the total omega 3 content of erythrocytes was about 160% over baseline. The omega 3 content of leukocytes after supplementation was much more variable ranging from -0.5% to 280% over baseline after 3 capsules per day and 37% to 416% over baseline after 6 capsules per day. Baseline Collagen/ADP aggregation was within the normal range in all patients: mean 72.4 sec (range 59-110) (normal- 70-118), no significant changes were noted at 6 months: mean 69.2 sec (range: 59-85). Baseline Collagen/EPI aggregation was elevated in 2 patients (>300 sec), the remaining patients had normal values with a mean of 100.3 sec (normal range: 74-193). At 6 months, Collagen/EPI aggregation showed a mean value of 129.3 sec (range 110-158), representing a mean 29.6% increase over baseline. Omega3 fatty acid supplements were generally well tolerated. Currently, 6 patients are up to 6 capsules/day and 2 are at 9 capsules/day. Two patients had Grade I intermittent diarrhea (1 patient at 6 capsules/day); 1 patient noted hand bruising.

Clearly, humans can consume enough omega 3 supplements to elicit biological activity as shown by the increase in fatty acid content of erythrocytes and leukocytes. No changes in Collagen/ADP aggregation was noted after 6 months of supplementation. A mild increase in Collagen/EPI aggregation is reported, with values that remained within the normal range, even in patients also medicated with aspirin. Studies are in progress to determine effects on NFkB activity and lipid peroxidation.

No relevant conflicts of interest to declare.