Sex and menopausal status influence human dietary requirements for the nutrient choline

Abstract

Background: Although humans require dietary choline for methyl donation, membrane function, and neurotransmission, choline can also be derived from the de novo synthesis of phosphatidylcholine, which is up-regulated by estrogen. A recommended Adequate Intake (AI) exists for choline; however, an Estimated Average Requirement has not been set because of a lack of sufficient human data.

Objective: The objective of the study was to evaluate the dietary requirements for choline in healthy men and women and to investigate the clinical sequelae of choline deficiency.

Design: Fifty-seven adult subjects (26 men, 16 premenopausal women, 15 postmenopausal women) were fed a diet containing 550 mg choline x 70 kg(-1) x d(-1) for 10 d followed by <50 mg choline x 70 kg(-1) x d(-1) with or without a folic acid supplement (400 microg/d per randomization) for up to 42 d. Subjects who developed organ dysfunction during this diet had normal organ function restored after incremental amounts of choline were added back to the diet. Blood and urine were monitored for signs of toxicity and metabolite concentrations, and liver fat was assessed by using magnetic resonance imaging.

Results: When deprived of dietary choline, 77% of men and 80% of postmenopausal women developed fatty liver or muscle damage, whereas only 44% of premenopausal women developed such signs of organ dysfunction. Moreover, 6 men developed these signs while consuming 550 mg choline x 70 kg(-1) x d(-1), the AI for choline. Folic acid supplementation did not alter the subjects' response.

Conclusion: Subject characteristics (eg, menopausal status) modulated the dietary requirement for choline, and a daily intake at the current AI was not sufficient to prevent organ dysfunction in 19 of the subjects.

FIGURE 1

Study design. The choline content of the baseline, depletion, and repletion diets is indicated. Subjects who developed organ dysfunction when fed the low-choline depletion diet were fed graded increasing intakes of choline for 10 d each until signs of organ dysfunction resolved: 137.5 mg choline · 70 kg⁻¹ · d⁻¹ [25% of the Adequate Intake (AI)], 275 mg choline · 70 kg⁻¹ · d⁻¹ (50% of the AI), 412.5 mg choline · 70 kg⁻¹ · d⁻¹ (75% of the AI), and finally 550 mg choline · 70 kg⁻¹ · d⁻¹ (100% of the AI). The baseline diet provided 400 dietary folate equivalents (DFE)/d. The choline-depletion and -repletion diets provided 100 DFE/d. On day 11, the subjects were randomly assigned to receive a placebo or a 400-μg folic acid supplement for the remainder of the study.

FIGURE 2

The number of subjects whose choline status returned to normal at each dietary choline intake. The subjects were treated as described in the legend for Figure 1. There was considerable variation in dietary choline requirements between the subjects. Those who manifested signs of organ dysfunction in response to the baseline or low-choline diet (depletion phase) became replete after graded increases in choline intakes were fed and signs of organ dysfunction resolved, if stopping rules did not dictate immediate advancement to a 100% or ad libitum repletion diet.