Determining the factors that control food web interactions is a key issue in ecology. The empirical relationship between nutrient loading (total phosphorus) and phytoplankton standing stock (chlorophyll a) in lakes was described about 30 years ago and is central for managing surface water quality. The efficiency with which biomass and energy are transferred through the food web and sustain the production of higher trophic levels (such as fish) declines with nutrient loading and system productivity, but the underlying mechanisms are poorly understood. Here we show that in seston (fine particles in water) during summer, specific ω3-polyunsaturated fatty acids (ω3-PUFAs), which are important for zooplankton, are significantly correlated to the trophic status of the lake. The ω3-PUFAs octadecatetraenoic acid, eicosapentaenoic acid (EPA) and docosahexaenoic acid, but not α-linolenic acid, decrease on a double-logarithmic scale with increasing total phosphorus. By combining the empirical relationship between EPA-to-carbon content and total phosphorus with functional models relating EPA-to-carbon content to the growth and egg production of daphnids, we predict secondary production for this key consumer. Thus, the decreasing efficiency in energy transfer with increasing lake productivity can be explained by differences in ω3-PUFA-associated food quality at the plant-animal interface.