Publication: A cell-based evaluation of a NEAA formulation as a non-bioactive control for activation and stimulation of muscle protein synthesis

Research Impact:  In scientific research it is important to include control conditions in good study design in order to answer the research question effectively. In the case of dietary or nutrition studies, often a no feeding or placebo group is included. However, in many cases, dietary compounds are likely to be more bioactive at the physiological level than nothing at all. In the case of protein, if researchers are trying to establish if a protein has a particular bioactivity, the European Food Safety Authority (EFSA) has stated that to establish bioactivity, all proteins should be compared against another protein source which has the same nitrogen component (isonitrogenous) rather than less appropriate controls such as no calorie placebos or other macronutrients such as carbohydrates. Therefore, we undertook to develop a negative control which was isonitrogenous to milk derived protein hydrolysates for use in our studies. We know that essential amino acids (EAA) are potent stimulators of muscle protein synthesis (MPS) which has an impact on muscle hypertrophy, however non-essential amino acids (NEAA) do not stimulate MPS . We developed a formulation which matched the amino acid content of milk derived proteins, minus the EAA component, comprised only of NEAAs. This study evaluated the effect of an isonitrogenous NEAA formulation on MPS using a cell based model and compared it to a bioactive protein hydrolysate. What we found is that this formulation did not stimulate or result in increased MPS in skeletal muscle cells, whereas our comparator protein hydrolysate increased MPS in our model. This establishes the isonitrogenous NEAA formulation as an excellent negative control for use in future protein supplementation MPS studies.

Patel, B., Pauk, M., Amigo-Benavent, M., Nongonierma, A.B., Fitzgerald, R.J., Jakeman, P.M. and Carson, B.P., 2019. A cell-based evaluation of a non-essential amino acid formulation as a non-bioactive control for activation and stimulation of muscle protein synthesis using ex vivo human serum. BioRxiv, p.713768. DOI: 10.1371/journal.pone.0220757