The present population-based study comprising 665 middle-aged subjects showed that serum levels of both n-3 and n-6 PUFA, relative to total fatty acids, were associated with lipoprotein particle concentrations and sizes. Longitudinal changes in these fatty acid proportions paralleled various changes in lipoprotein particle numbers and sizes. This appears to be the first study showing longitudinal association between changes in serum PUFA levels and lipoprotein particle concentrations in a population consuming their habitual diet. The baseline results of the present study are in line with the previous cross-sectional study of 1098 men conducted by Choo et al. .
Previously, Motoyama et al. found in the population-based large study that n-6 and n-3 PUFAs were inversely related to serum triglycerides which are carried by VLDL . VLDL lipoprotein has been found to associate with increased cardiovascular risk . In line with the previous study by Choo et al.  higher n-6 PUFA concentration at baseline associated with smaller VLDL particle size and concentration in the present study. However there was not a clear association between n-3 PUFAs and VLDL particles at baseline. In addition, the strongest longitudinal correlations were found for the negative associations between n-6 PUFAs and VLDL particle concentration and size. Small low-density lipoprotein particles have been shown to be a cardiovascular risk factor predicting coronary artery disease and events [16–18]. In the present study, there was not a difference in LDL particle sizes between n-3 tertiles at baseline and the difference between n-6 PUFA tertiles was only modest. However, the present findings suggest that the change of PUFA levels, especially n-6 PUFAs, associate positively with the change of LDL particle size. Increased circulating levels of n-3 and n-6 PUFAs may contribute to favorable non-HDL (LDL and VLDL) particle changes.
Serum PUFA concentrations showed an association with mean HDL particle size at baseline. In addition, the change of n-3 PUFAs correlated with the change in HDL particle size. The FinnTwin-study suggested that a higher consumption of n-3 PUFA was related to changes in HDL subspecies toward a larger mean particle size in men . That association remained significant in analyses controlling for genetic and environmental influences and for confounding factors like BMI, smoking and physical activity. Here we were able to control for additional potential confounding factors which yielded consistent findings with the FinnTwin-study.
The serum concentrations of fatty acids are generally regarded as markers of dietary intake although adiposity and genetics may contribute . We did not assess the macronutrient dietary intake from this population. In the population-based Kuopio Ischemic Heart Disease (KIHD) study dietary intake of PUFAs correlated with serum PUFAs (r = 0.50) . The KIHD study was performed in an area in close proximity of this study area and subjects in both KIHD and in this study share similar socio-demographic characteristics. The Cardiovascular Risk in Young Finns Study provided consistent findings about the relationship between dietary intake and serum levels of PUFAs as quantified by NMR spectroscopy . We assume that serum PUFA levels in the present study primarily reflect dietary intake of PUFAs. It is possible that most pronounced change in the dietary habits was the change in fat quality. In the lake area of this study population, the potential increased intake of n-3 PUFAs was most likely from the lean white fish . However, these assumptions cannot be confirmed based on these data because we did not have the measurement of diet.
The observational nature of this study, with only two health checkups and missing dietary intake information may be taken as a limitation. However, the present study represents a general population with several years of follow-up and with measurements of the circulating lipoprotein particle profile as well as PUFAs conducted for all baseline and follow-up samples at the same time.
In conclusion, at the population level, the 6-year relative increases in serum levels of both n-3 and n-6 PUFAs are associated with concurrent favorable changes in the lipoprotein particle profile among men and women with a mean age of 46 years.