Dietary phenylalanine requirements during early and late gestation in healthy pregnant women

Abstract

Background: Phenylalanine is an indispensable amino acid and, via tyrosine, is the precursor for the neurotransmitters dopamine, norepinephrine, and epinephrine. Currently, dietary requirements for phenylalanine during pregnancy are unknown.

Objectives: This study's aim was to determine phenylalanine requirements (in the presence of excess tyrosine) during early and late gestation using direct amino acid oxidation (DAAO; with l-[1-13C]phenylalanine) and indicator amino acid oxidation (IAAO; with l-[1-13C]leucine).

Methods: Twenty-three healthy women (age: 30.4 ± 3.1 y, mean ± SD) were studied at a range of phenylalanine intakes (5.5-30.5 mg · kg-1 · d-1 in early and late pregnancy using DAAO, and 2.5-30.5 mg · kg-1 · d-1 in late pregnancy using IAAO) for a total of 76 study days. Test intakes were provided as 8 isocaloric and isonitrogenous meals with 1.5 g · kg-1 · d-1 protein and energy at 1.7 times the measured resting energy expenditure. Breath samples were analyzed on an isotope ratio mass spectrometer for 13C enrichment. Phenylalanine requirement was determined using a 2-phase linear regression crossover model to identify a breakpoint in 13CO2 production (representing the mean requirement) in response to phenylalanine intakes.

Results: Phenylalanine requirement during early pregnancy was determined to be 15 mg · kg-1 · d-1 (95% CI: 10.4, 19.9 mg · kg-1 · d-1); during late pregnancy, it was determined to be 21 mg · kg-1 · d-1 by DAAO (95% CI: 17.4, 24.7 mg · kg-1 · d-1) and IAAO (95% CI: 10.5, 32.2 mg · kg-1 · d-1).

Conclusions: Our results suggest a higher requirement (40%) for phenylalanine during late pregnancy than during early pregnancy. Moreover, the early pregnancy requirements are higher than the previous adult male requirement (9.1 mg · kg-1 · d-1; 95% CI: 4.6, 13.6 mg · kg-1 · d-1), although the 95% CIs overlap. Both DAAO and IAAO methods provided similar breakpoints in late pregnancy, showing that the DAAO method was appropriate even though low phenylalanine intakes could not be tested. These results have potential implications for gestation stage-specific dietary phenylalanine recommendations in future.This trial was registered at clinicaltrials.gov as NCT02669381.

Keywords: amino acid requirements; phenylalanine; pregnancy; stable isotopes; tyrosine.

FIGURE 1

Estimated average requirement of phenylalanine in early gestation using the direct amino acid oxidation method in healthy pregnant women. Biphase linear regression crossover analysis of l-[1-¹³C]phenylalanine tracer oxidation (F¹³CO₂, µmol · kg⁻¹ · h⁻¹) was used to determine the phenylalanine requirement using the mixed and regression procedure in SAS (SAS/STAT version 9.4). Phenylalanine requirements were determined to be 15 mg · kg⁻¹ · d⁻¹ (R² = 0.87; 95% CI: 10.4, 19.9 mg · kg⁻¹ · d⁻¹; n = 9, individual study days = 26). Dashed line indicates the mean requirement.

FIGURE 2

Estimated average requirement of phenylalanine in late gestation using the direct amino acid oxidation method in healthy pregnant women. Biphase linear regression crossover analysis of l-[1-¹³C]phenylalanine tracer oxidation (F¹³CO₂, µmol · kg⁻¹ · h⁻¹) was used to determine the phenylalanine requirement using the mixed and regression procedure in SAS (SAS/STAT version 9.4). Phenylalanine requirements were determined to be 21 mg · kg⁻¹ · d⁻¹ (R² = 0.79; 95% CI: 17.4, 24.7 mg · kg⁻¹ · d⁻¹; n = 9, individual study days = 25). Dashed line indicates the mean requirement.

FIGURE 3

Estimated average requirement of phenylalanine in late gestation using the indicator amino acid oxidation method in healthy pregnant women. Biphase linear regression crossover analysis of l-[1-¹³C]leucine tracer oxidation (F¹³CO₂, µmol · kg⁻¹ · h⁻¹) was used to determine the mean phenylalanine requirement using the mixed and regression procedure in SAS (SAS/STAT version 9.4). Phenylalanine requirements were determined to be 21 mg · kg⁻¹ · d⁻¹ (R² = 0.37; 95% CI: 10.5, 32.2 mg · kg⁻¹ · d⁻¹; n = 13, individual study days = 25). Dashed line indicates the mean requirement.

FIGURE 4

Plasma concentrations of phenylalanine and tyrosine in early pregnancy in response to graded phenylalanine intakes in healthy pregnant women. Linear regression analysis of (A) phenylalanine concentrations (R² = 0.78) and (B) tyrosine concentrations (R² = 0.03; mean ± SD: 48.8 ± 8.7) (n = 9, individual study days = 26).

FIGURE 5

Plasma concentrations of phenylalanine and tyrosine in late pregnancy (when employing the direct amino acid oxidation method) in response to graded phenylalanine intakes in healthy pregnant women. Linear regression analysis of (A) phenylalanine concentrations (R² = 0.82) and (B) tyrosine concentrations (R²  = 0.009; mean ± SD: 55.5 ± 11.2 ) (n = 9, individual study days = 25).

FIGURE 6

Plasma concentrations of phenylalanine and tyrosine in late pregnancy (when employing the indicator amino acid oxidation method) in response to graded phenylalanine intakes in healthy pregnant women. Linear regression analysis of (A) phenylalanine concentrations (R² = 0.79) and (B) tyrosine concentrations (R² = 0.023; mean ± SD: 58.3 ± 11.6) (n = 13, individual study days = 25).