Effects of a diet based on the Dietary Guidelines on vascular health and TMAO in women with cardiometabolic risk factors

Authors: KRISHNAN, SRIDEVI - University Of California, Davis; Gertz, Erik; ADAMS, SEAN - University Of California, Davis; Newman, John; PEDERSEN, THERESA - University Of California, Davis; Keim, Nancy; Bennett, Brian

Submitted to: Nutrition Metabolism and Cardiovascular Disease
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/8/2021
Publication Date: 9/20/2021
Citation: Krishnan, S., Gertz, E.R., Adams, S.H., Newman, J.W., Pedersen, T.L., Keim, N.L., Bennett, B.J. 2021. Effects of a diet based on the Dietary Guidelines on vascular health and TMAO in women with cardiometabolic risk factors. Nutrition Metabolism and Cardiovascular Disease. 32(1):210-219. https://doi.org/10.1016/j.numecd.2021.09.013.
DOI: https://doi.org/10.1016/j.numecd.2021.09.013

Interpretive Summary: Problem: The CDC reports that about 1 in 4 deaths in the US is from heart disease. While it is important to study how best to manage and cure heart disease, it is equally, if not more, important to understand how to prevent it. The health of blood vessels that carry nutrients to all body tissues is a large part of heart health. Diet is an important lifestyle aspect that can cause, make worse, or prevent heart disease. The Dietary Guidelines for Americans publishes, once every 5y since 1980, diet advice that can help prevent heart disease. This diet advice is in the form of recommended servings of different foods in order to meet all nutrient requirements, while limiting intake of some foods that need to be consumed in moderation. And yet, the diet prescribed by the guidelines has not been rigorously tested to verify if it does work as intended. Accomplishment: Here, we studied the effect of eating a diet, which is based on the dietary guidelines for 8 weeks, in comparison to eating a diet that is considered a 'typical' American diet. Primarily, the study focused on measuring blood vessel health (endothelial function), and small molecules (in particular, Trimethylamine oxide or TMAO) that originate from the gut microbes with supposed ability to worsen blood vessel health (among other adverse effects). We also calculated a 10-y risk for heart disease incidence, using an established index (called the Framingham risk score). These were measured before and after the study, which was done in 44 women, who were overweight/obese and had at least 1 risk factor for developing heart disease in the future. The women also maintained body weight, so that whatever change occurs in their heart health, is due to changing diet, but not due to weight loss. Following the diet recommended by the dietary guidelines for Americans, there was a reduction in the calculated 10-y heart disease risk score, but there were no changes in measures of TMAO or blood vessel health. Contribution of accomplishment to solving the problem. Following the Dietary Guidelines only for 8-weeks, in women who continued to remain overweight or obese, did not affect blood vessel health, but hinted at reduction in 10-y risk for heart disease, probably by affect other factors that cause heart disease. This suggests that the dietary guidelines need to be tested in longer studies, and with both men and women, and with and without weight loss, to see which approach helps reduce heart disease risk the most.

Technical Abstract: Background: Endothelial dysfunction is an early indicator of cardiovascular disease, and recent evidence suggests circulating trimethylamine oxide (TMAO) is capable of inducing endothelial dysfunction. Objective: The objective was to determine whether consumption of a diet patterned after the 2010 Dietary Guidelines for Americans (DGA), as compared to a typical American Diet (TAD), would improve endothelial function, reduce cardiovascular disease risk, and plasma TMAO concentrations. Methods: A randomized, double-blind, 8-wk controlled feeding intervention was conducted in overweight/obese women selected based on indices of insulin resistance and/or dyslipidemia. Women were randomly assigned to a DGA or TAD group (n = 22/group). The TAD diet was based on average adult intake from the NHANES 2009–2010. EndoPAT was used to measure endothelial function (reactive hyperemia index (RHI) measure of endothelial function) and augmentation index (AI@75) – measure of arterial stiffness) at wk0 (baseline, pre-intervention) and wk8 of diet intervention. Plasma samples were collected to measure parameters required to calculate Framingham risk score (FRS), vascular age, and TMAO and its precursor metabolites (choline, carnitine and betaine) concentrations. Results: FRS was lower in DGA at wk8 compared to wk0 (DGA wk8: 4.8 ± 0.6% vs. DGA wk0: 6.1 ± 1.0%, p = 0.032). TAD wk8 value (4.1 ± 0.4, p = 0.337), did not differ from DGA wk8 value. nor were TAD wk0 vs. wk8 different. The same was true for vascular age (DGA wk0: 54.2 ± 4.0 vs. wk8: 50.5 ± 3.1 (p = 0.051), vs. TAD wk8: 47.7 ± 2.3). There were no significant changes in RHI or AI@75 between groups or weeks. Plasma TMAO concentrations were not different between the DGA and TAD diets. Conclusion: Consumption of a diet based on the 2010 Dietary Guidelines for Americans for 8 weeks did not improve endothelial function or reduce plasma TMAO, and any changes in 10-y risk score was likely not due to the effect of diet on endothelial function.