Fatty acid status in adolescents: interplay between diet and genes

Both quantity and quality of dietary fatty acid (FA) intake have been associated with several non-communicable diseases in humans, such as cardiovascular disease, cancer, neurologic disorders, inflammatory and auto-immune diseases. Pathophysiologic mechanisms underlying these associations are currently not completely understood. However, through their function as lipid mediator and modulator of gene transcription, FA might interfere in and modulate the disease processes. FA intake is one of the determinants of the FA serum status, which ultimately determines these effects. Other factors, such as the genetic variants of certain genes, sex, body composition, etc, which influence the metabolism of the FA, have been shown to play a role as well. The general aim of this thesis was to further elaborate the current knowledge on the influence of dietary FA intakes and its interaction with polymorphisms in the FADS1 and LIPC gene, on the FA serum status in the healthy population. This insight could help us to identify possible mechanisms to modulate the FA serum status and as such help to prevent or treat the non-communicable diseases, mentioned above. Although most of these diseases usually manifest in adulthood, cardiometabolic risk factors may already appear at younger age and may track into adulthood. As such, this thesis focused on adolescents and was imbedded in the ‘Healthy Lifestyle in Europe by Nutrition in Adolescence Cross-Sectional Study’ (HELENA-CSS), which had as main objective to obtain reliable and comparable data on nutrition- and health-related parameters in a sample of 3528 European adolescents (aged 12.5-17.5 years). In a first study, the usual FA intake and its main food sources were described in this adolescent population and the variation in intake as a function of non-dietary factors, such as sex, age, body composition, sexual maturation, socio-economic status and physical activity was explored. Compared to the recommendations of the Food and Agriculture Organization, almost all adolescents had an excessive intake of saturated fatty acids (SFA) (99.8%) and an inadequate intake of n-3 FA (>50%). In general, girls had a more beneficial FA intake pattern; however, the differences between sexes disappeared in the older aged adolescents (15-17.5 years) except for the poly-unsaturated fatty acid (PUFA) intake, which continued to be higher in the older adolescent female population. Furthermore, chronological age was a stronger determinant of FA intake than sexual maturation and no differences in fat intake were observed as a function of maternal education level or body composition, measured as BMI z-score or body fat percentage. In the male population, fat and fatty acid intake was inversely related to their level of physical activity. The main contributors to total fat, SFA, mono-unsaturated fatty acids (MUFA) and PUFA intake were meat, dairy products and cakes/pies/biscuits. Generally, meat was a slightly higher contributor in boys whilst cakes, pies and biscuits as well as nuts and seeds seemed to be of higher importance in girls. Another study indicated that, although adolescents with a better overall dietary quality had higher levels of total fat intake and SFA than their counterparts with a less beneficial dietary pattern, they derived their fat intake from more recommended food sources. In particular a higher consumption of dairy products and lower consumption of snacks and sauces was observed in adolescents with a Diet Quality Index for Adolescents (DQI-A) score in the upper quartile. In a second study, the influence of specific food intake on the serum phospholipid (PL) FA concentration was investigated by exploring the correlations and the amount of variance that was explained by these nutritional factors. It was demonstrated that the percentage of variation in PL FA serum levels due to dietary intake varied from 14.2% for n-3 FA to 7.0% for total MUFA. For arachidonic acid (AA) and linoleic acid (LA) this was respectively 10.8% and 10.7%. This indicated that dietary intake is indeed a factor of considerable importance on the FA serum status but that other determinants also interfere such as the homeostatic control mechanisms and a wide array of genetic, environmental and life-style factors. In a final study the influence of genetic predisposition on the PL FA serum status was explored. In the HELENA study population it was demonstrated that genetic variability in the rs174546 single nucleotide polymorphism (SNP) of the FADS1 gene, encoding for the Δ5-desaturase, was associated with higher serum PL concentrations of LA and α-linolenic acid (ALA) and lower levels of AA and eicosapentaenoic acid (EPA). In the LIPC gene, the minor allele of the rs1800588, resulting in a lower activity of hepatic lipase, was associated with higher levels of stearic acid. Furthermore, an interaction effect between the rs1800588 SNP and dietary LA intake as well as between this SNP and estimated VO2max on the serum PL AA levels was demonstrated. Overall, these findings indicated that the dietary FA intake influences the FA serum status by its direct effect as source or precursor of certain FA, but that it also exerts an important role by the interaction with certain genes. This interplay between diet and genes demonstrated that individuals with a certain genetic background would require different amounts of individual FA to achieve the same biological effect and thus might benefit from so called “personalized nutrition”. Moreover, it can be concluded that other factors such as the global dietary pattern and the physical activity of an individual are of importance and that it remains essential to further encourage compliance to these general public health guidelines. More specifically, attention should be drawn to higher intakes of n-3 LCPUFA and lower intakes of SFA in adolescent age. Nevertheless, these findings were subject to some limitations, such as the lack of accuracy of the estimated FA intake, the variation in international recommendations, not being able to correct for alcohol intake and smoking habits, the limited comparability to other studies assessing lipid pools other than phospholipids and the limited number of genetic variants that have been analysed. As such, future studies should be extended to the investigation of other polymorphisms in the LIPC and FADS genes as well as to other genes; and the gene-environment effect on hard endpoints, such as the development of the above mentioned diseases, should be assessed. Moreover, in dietary intervention and supplementation studies, genetic variability should be considered. Also, in supplementation studies it should be examined whether pharmaceutical doses of FA may have adverse effects. Ultimately, based on such results we might be able to deduce in what form and combination, as supplement or via the diet, we need to supply these nutrients to obtain maximal health benefit with minimal risk.