Glycine, a Dispensable Amino Acid, Is Conditionally Indispensable in Late Stages of Human Pregnancy

Abstract

Background Recently, we showed that there are higher protein, lysine, and phenylalanine requirements in late stages of pregnancy compared with early stages. Animal studies have suggested an increased dietary need for specific dispensable amino acids in pregnancy; whether such a need exists in human pregnancies is unknown. Objective The objective of the current study was to examine whether healthy pregnant women at midgestation (20–29 wk) and late gestation (30–40 wk) have a dietary demand for glycine, a dispensable amino acid, using the indicator amino acid oxidation method and measurement of plasma 5-oxoproline concentrations. Methods Seventeen healthy women (aged 26–36 y) randomly received different test glycine intakes (range: 5–100 mg·kg−1·d−1) during each study day in midgestation (∼26 wk, n = 17 observations in 9 women) and late gestation (∼35 wk, n = 19 observations in 8 women). Diets were isocaloric with energy at 1.7 × resting energy expenditure. Protein was given as a crystalline amino acid mixture based on egg protein composition at current estimated average requirement (EAR; 0.88 g·kg−1·d−1). Breath samples were collected at baseline and isotopic steady state to measure oxidation of L-[1–13C]phenylalanine to 13CO2 (F13CO2). Plasma was collected at the sixth hour of the study day. Linear regression crossover analysis and simple linear regression were used to assess responses in F13CO2 and plasma 5-oxoproline concentrations to different glycine intakes. Results No statistically significant responses were observed in midgestation. However, in late gestation, lower glycine intakes resulted in higher rates of F13CO2 (suggesting low protein synthesis) with a breakpoint for phenylalanine oxidation at >37 mg glycine·kg−1·d−1 and higher plasma 5-oxoproline (suggesting low glycine availability) with a breakpoint >27 mg glycine·kg−1·d−1. Conclusions The findings suggest that glycine should be considered a “conditionally” indispensable amino acid during late gestation, especially when protein intakes are at 0.88 g·kg−1·d−1, the current EAR. This trial was registered at clinicaltrials.gov as NCT02149953.

Is It Time to Reconsider the U.S. Recommendations for Dietary Protein and Amino Acid Intake?

“…Thus, even the relatively high protein intake of 1.13 g/kg/d, supplying about 3 g glycine/d, coupled with glycine from biosynthesis, is unlikely to meet biological requirements for optimal function. In concordance, an IAAO study showed that glycine intakes less than 37 mg/kg/d result in increased phenylalanine oxidation among late gestation pregnant women [ 95 ] (see next section). Arguments for glycine supplementation have also been made based on the observation that tissue glycine levels are often lower than the glutathione synthase Michaelis constant (K m ) for glycine [ 96 ].…”

“…Yet, swine studies showed greater demand during pregnancy for the two dispensable amino acids glutamine and arginine, suggesting they were conditionally essential [ 130 ]. Rasmussen et al [ 95 ], tested glycine, a dispensable amino acid, using IAAO in the pregnant population during mid- and late gestation. During mid-gestation (~26 wks), a glycine-restricted diet did not affect whole-body protein synthesis, suggesting de novo glycine synthesis from interconversion of other amino acids such as serine was adequate for the maternal needs [ 95 ].…”

“…Rasmussen et al [ 95 ], tested glycine, a dispensable amino acid, using IAAO in the pregnant population during mid- and late gestation. During mid-gestation (~26 wks), a glycine-restricted diet did not affect whole-body protein synthesis, suggesting de novo glycine synthesis from interconversion of other amino acids such as serine was adequate for the maternal needs [ 95 ]. However, in late gestation, the restriction of glycine did impact whole body protein synthesis.…”

“…This would suggest the requirement for late gestation should be higher than these estimates. Rasmussen et al [ 95 ], advised the lower calculated value (>37 mg/kg/d) may be due to provision of total protein at 0.88 g/kg/d during the test. Inadequate provision of total nitrogen, which at 0.88 g/kg/d is the EAR, not the population-safe level of protein, may have impacted the de novo synthesis of glycine in later gestation when protein needs are higher.…”

Editorial: Beyond traditional roles for amino acids

“…Likewise, normalizing plasma glycine concentrations improves insulin sensitivity and thus, simple interventions such as dietary glycine supplementation may prove effective, although it is yet to be experimentally determined. Related to this is the fact that the simplest of amino acids from a structural point, glycine – a dispensable amino acid, has been shown to be a conditionally indispensable amino acid in infants in the past, and most recently in healthy pregnant women in later stages of pregnancy [9]. Thus, it is likely that in disease there is a dietary requirement for glycine and needs to be quantitatively confirmed in future.…”