Moderate choline intake lowers heart disease risk

A recent BMC Public Health study examines data from the National Health and Nutrition Examination Survey (NHANES) database to elucidate the association between atherosclerotic cardiovascular disease (ASCVD) and dietary choline.

Study: An inverse association of dietary choline with atherosclerotic cardiovascular disease among US adults: a cross-sectional NHANES analysis. Image Credit: Danijela Maksimovic / Shutterstock.com

What is choline?

Choline is an essential nutrient that is a precursor for several important biological molecules, including acetylcholine, which is a neurotransmitter involved in memory, mood, and muscle control. Choline is also a precursor for phosphatidylcholine and sphingomyelin, both of which are major phospholipids present within cell membranes.  

Choline has limited endogenous synthesis; therefore, it is crucial to consume dietary sources of choline to meet all physiological needs. Choline is concentrated in high-protein foods, including beef, fish, milk, eggs, cruciferous vegetables, legumes, and nuts.

Existing evidence on the relationship between choline and ASCVD is unclear. For example, some studies have shown that choline influences the trimethylamine N-oxide (TMAO) pathway, thereby increasing the risk of cardiac dysfunction, stroke, and heart failure. Comparatively, other studies have reported the beneficial role of choline in mitigating cardiac hypertrophy by regulating of metabolic remodeling.

Metabolic syndrome (MetS), which describes a cluster of conditions including atherogenic dyslipidemia, high fasting blood glucose levels, hypertension, and obesity that occur together, currently affects 20-30% of adults throughout the world. The presence of MetS increases the risk of ASCVD, as well as myocardial infarction, coronary heart disease, and stroke.

About the study

The key role of MetS in atherosclerosis progression warrants additional studies to elucidate how choline affects the development of this condition. To this end, the researchers of the current study examined how choline intake affects the risk of ASCVD in adults and the development of MetS.

The current cross-sectional study comprised 5,525 individuals from the NHANES database between 2011 and 2018. A total of 510 participants were grouped into the non-ASCVD group, whereas 5,015 individuals constituted the ASCVD group. A combination of univariate, multivariate, and logistic regression methods was used to analyze the results.

Study findings

No significant correlation was observed between choline intake and MetS. However, the likelihood of congestive heart failure and stroke was lower for individuals in the third quartile of choline intake. This effect was reversed when choline intake exceeded 342 mg/d, thereby augmenting the risk of ASCVD.

The adequate choline intake for beneficial effects was 244 mg/d for women and 367 mg/d for men. Sub-group analyses revealed that men experienced more protective effects through a high intake of choline.

In women, estrogen facilitates the synthesis of endogenous phosphatidylcholine, which could be responsible for the reduced incidence of organ dysfunction symptoms in pre-menopausal women as compared to men and post-menopausal women. This finding needs to be interpreted with caution, as no significance was observed for the interaction between choline intake and sex in the logistic analysis.

Choline plays a crucial role in the pathogenesis of several chronic diseases and neurodevelopment, as choline deficiency could lead to muscle damage and fatty liver. Data from the current study indicates that excessive choline intake did not correlate with an increased risk of stroke. The researchers hypothesize that the brain may limit the effects of excessive choline intake either by regulating its net absorption and release of choline or through rapid metabolism.

As compared to previous reports, the PREDIMED study observed that plasma choline was associated with an increased risk of heart failure. In other animal studies, atherosclerosis and heart failure were observed following supplementation with TMAO and choline.

Furthermore, the SURDIAGENE study reported the absence of a statistically significant association between heart failure and choline in type 2 diabetes patients. Thus, the ability of dietary choline to increase plasma TMAO levels could contribute to choline’s contradictory role in cardiovascular disease.

Conclusions

An inverse and non-linear association between choline and ASCVD was observed in American adults, with this effect less pronounced in males. Taken together, the study findings motivate the development of individual-specific dietary recommendations, which could reduce the risk of ASCVD.

One limitation of the present study is that choline intake data were obtained through a food types and quantities questionnaire. Thus, the calculation of choline intake from this data could be inaccurate due to heterogeneities regarding choline absorption and metabolism.

Another limitation is due to the lack of information on plasma TMAO levels, as direct causality between choline intake and TMAO could not be determined. The potential role of residual confounding factors was also not assessed.

Longitudinal studies are needed to establish causality between choline intake and ASCVD. Future studies should also assess the impact of excessive choline intake on cardiometabolic health.