Does essential amino acid supplementation cause insulin resistance?

Study under review: Effect of essential amino acid supplementation and aerobic exercise on insulin sensitivity in healthy older adults: A randomized clinical trial.

Aging is often characterized by a progressive loss of muscle mass and strength (a phenomenon called sarcopenia^[1]) and an increase in body fat^[2] levels. This combination of sarcopenia and excess fat mass has been termed sarcopenic obesity^[3], and has been associated with a number of negative health effects, including insulin resistance^[4].

There are many causes^[5] of sarcopenic obesity in older adults, including physical inactivity, excessive energy intake, hormonal changes, insufficient protein intake, and chronic inflammation, while interventions^[6] for its prevention and treatment include regular physical activity and an increase in protein/amino acid intake. These interventions can help improve many of the underlying causes that lead to sarcopenic obesity as laid out in Figure 1.

Although higher protein intakes have consistently been found to exert positive effects^[7] on body composition, it has been suggested that a high protein intake may increase the risk of insulin resistance. This is because (i) amino acids, especially branched chain amino acids (i.e. leucine, isoleucine, and valine) and their metabolites, have been found^[8] to accumulate in the blood of obese, compared to lean, people, and have been identified as predictors^[9] of insulin resistance, (ii) in vitro animal data have demonstrated that leucine can impair^[10] insulin-mediated glucose uptake, and (iii) an excess of amino acids in the blood in response to amino acid infusion has been found to reduce^[11] the insulin-induced removal of glucose from the blood into tissues in humans.

With the above in mind, a chronically high intake of protein/amino acids could, theoretically, worsen age-related insulin resistance, and potentially lead to type 2 diabetes. Consequently, older adults could be promoting improvements in insulin sensitivity through regular physical activity, and, at the same time, counteracting these improvements through an increase in essential amino acid intake. However, although this hypothesis may, theoretically, make sense, there is currently no available scientific research directly examining it. The study under review aimed to fill this knowledge gap by investigating the effects of aerobic exercise alone, essential amino acid (EAA) supplementation alone, or the combination of the two on insulin sensitivity in healthy older adults.

Aging is often characterized by a progressive loss of muscle mass and an increase in fat mass (i.e. sarcopenic obesity), which may potentially contribute to the development of insulin resistance. Lifestyle changes to prevent or treat sarcopenic obesity and the associated insulin resistance include regular physical activity and higher protein intakes. However, a high intake of dietary amino acids may promote insulin resistance, thereby counteracting the beneficial effects of exercise. As no research directly examining this hypothesis has been conducted to date, the study under review aimed to fill this gap by investigating the effects of aerobic exercise alone, essential amino acid (EAA) supplementation alone, or the combination of the two on insulin sensitivity in healthy older adults.