Oral choline increases choline metabolites in human brain

Abstract

Choline, a precursor of acetylcholine and phosphatidylcholine, is largely obtained from the diet. Animal studies demonstrate increased choline metabolites in brain following oral administration. Several proton magnetic resonance spectroscopy (¹H-MRS) reports differ as to whether similar increases are observable in human subjects. This study was designed to minimize intra-subject variance and thereby maximize the ability to determine if a significant increase in brain choline can be detected after choline ingestion. ¹H-MRS was performed continuously for 2.5 h on 11 healthy young males following choline ingestion. Nine of the original subjects returned for identical scans without choline ingestion. Following oral choline, there was a statistically significant increase in the choline signal (Cho) measured from the left putamen, representing choline-containing compounds, as measured against creatine (Cr) or N-acetylaspartate (NAA). The mean increase in Curve maxima (C_max) is 6.2% for Cho/Cr and 3.0% for Cho/NAA. The Mean Time to C_max (T_max) was approximately 2 h after ingestion. A 3–6% increase in Cho by MRS likely corresponds to a 10–22% increase in phosphocholine, similar to findings in animal studies. In conclusion, a significant increase in choline-containing compounds in human brain can be detected by ¹H-MRS after choline ingestion in young subjects.

Introduction

Choline is a constituent of the neurotransmitter acetylcholine, as well as the cell membrane components phosphatidylcholine (PtdCho) and sphingomyelin. Very little choline is synthesized in brain. Rather, brain choline is obtained through dietary intake (Zeisel, 1992, Klein et al., 1993), with plasma choline transported across the blood-brain barrier by facilitated diffusion (Cornford et al., 1978, Millington and Wurtman, 1982, Klein et al., 1991, Löffelholz et al., 1993). Numerous studies in animals consistently observe an increase in choline and its metabolites in brain after choline administration. The amount of increase varies somewhat, depending upon the route of administration (intravenous, intraperitoneal, intra-arterial or oral), the amount given, the time period after administration, and the technique used to measure choline-containing compounds, but it generally ranges from 25 to 400% (Wecker and Dettbarn, 1979, Wecker and Schmidt, 1980, Millington and Wurtman, 1982, Mooradian, 1988, Klein et al., 1990, Klein et al., 1991, Klein et al., 1992, Klein et al., 1998). Our early studies, using proton magnetic resonance spectroscopy (¹HMRS) to non-invasively measure choline uptake in human subjects, showed increased choline in proportions similar to those seen for choline-containing compounds in animal studies (Cohen et al., 1995). However, subsequent studies show variable results, including some small increases that did not reach statistical significance (Tan et al., 1998, Dechent et al., 1999).

Whether human brain is dependent on choline uptake to the extent suggested in animal studies is important for understanding cholinergic regulation in psychiatric and neurologic disorders and aging. MRS studies can estimate the concentration of cytosolic choline-containing compounds in vivo in human brain. However, the variance between measurements in the same subject taken at different times may obscure changes in metabolite resonances. Consequently, we have performed a study designed to minimize intra-subject variance to determine if increases seen in the choline resonance in MRS studies are significant.