Blood coagulation in diabetes is known to be increased (1,2). Because levels of n-3 and n-6 polyunsaturated fatty acids (PUFAs) influence the parameters of blood coagulation, the aim of this study was to determine the effects of n-3 PUFA supplementation on coagulation and fibrinolytic factors in type 2 diabetic subjects. While it is not clear what the appropriate intake ratio of n-6 to n-3 PUFAs should be for diabetic subjects, it is known that the dietary intake ratio of n-6 to n-3 PUFAs is roughly 4:1 in Japanese subjects (3).
Ten subjects (six women and four men, average age 59.6 years) with type 2 diabetes participated in this study as inpatients. Their average BMI and HbA1c values were 20.9 ± 3.8 kg/m2 and 10.8 ± 1.1%, respectively. Their daily energy intake during the course of the study was 1,490 ± 166 kcal. After 2 weeks on the control diet, our subjects were placed on a diet in which 5 g linseed oil was added (in salads, miso soup, etc., without heating) in exchange for 5 g cooking oil. The ratio of PUFAs to saturated fatty acids in the subjects’ prestudy and study diets were 1.2 and 1.6, respectively, while the ratios of n-6 to n-3 PUFAs in their prestudy and study diets were 3.6 and 1.5, respectively. Blood samples were collected before and 14 days after initiation of the study. Plasmin α2-plasmin inhibitor complex (PPI) level and plasminogen activator inhibitor-1 (PAI-1) activity in plasma was measured using a latex photometric immunoassay, while thrombin antithrombin III complex (TAT) level was measured using an enzyme-linked immunoassay. Differences in these parameters obtained at the start and end of the study were analyzed using a paired t test; values were considered to be significant if the P value was <0.05. Values are expressed as the mean ± SD.
After 2 weeks on a linseed oil–supplemented diet, PPI level, PAI-1 activity, and TAT level fell significantly (0.72 ± 0.19 vs. 0.47 ± 0.14 μg/ml, P = 0.0009; 73.3 ± 37.5 vs. 51.6 ± 25.0 ng/ml, P = 0.02; and 9.6 ± 9.1 vs. 2.5 ± 1.1 ng/ml, P = 0.04; respectively).
Boberg et al. (4) reported that PAI-1 activity was increased in type 2 diabetic subjects after supplementation of their diet with 10 g eicosapentaenoic acid. Kelly et al. (5) reported that a diet containing flaxseed oil (60% α-linolenic acid) did not alter indexes of blood coagulation, i.e., bleeding time, prothrombin time, and partial prothrombin time. Chan et al. (6) showed that altering the dietary n-6–to–n-3 PUFA ratio had no effect on bleeding time. Our results, on the other hand, showed that a diet-induced reduction in the n-6–to–n-3 PUFA ratio affected parameters of blood coagulation and fibrinolysis. Finally, Freese et al. (7) reported that supplemental α-linolenic acid from vegetable oil and eicosapentaenoic and docosahexaenic acids from a marine source had similar effects on hemostatic factors. In conclusion, our results showed that PPI level, PAI-1 activity, and TAT level were significantly reduced in type 2 diabetic subjects that had their n-6–to–n-3 PUFA ratio lowered by dietary means.
