The gut flora or microbiota is undoubtedly crucial to the digestive process. However, there is growing interest in the role of the gut microbiota as an environmental factor influencing propensity for cardiometabolic disease. Studies have implicated the gut microbiota in susceptibility to obesity and insulin resistance; germ-free mice fed a high-fat, high-carbohydrate Western-style diet were protected against diet-induced obesity, glucose intolerance and insulin resistance.(1)
More recently, research has linked dietary lipid intake, the gut microbiota and increased risk for atherosclerosis.(2,3) Cholesterol-rich foods, such as egg yolks, contain phosphatidylcholine which is hydrolysed by phospholipase enzymes to release choline. The gut microbiota then convert choline to trimethylamine (TMA), which undergoes oxidation in the liver to trimethylamine N-oxide (TMAO), released into the plasma (Figure
In mice susceptible to atherosclerosis fed a diet supplemented with phosphatidyl choline, there was an increase in plasma levels of TMAO concomitant with increased atherosclerotic plaque development. Mechanistically, increased dietary choline was associated with suppression of multiple macrophage scavenger receptors which protect against atherosclerosis.3 These data therefore implicate excess dietary choline as an emerging modifiable risk factor for cardiovascular disease, mediated by the gut microbiota.
These findings may be relevant in the light of the recent FOCUS paper
(4), which showed an association between egg yolk consumption and carotid plaque burden. Individuals consuming 3 or more eggs per week had a significantly higher plaque burden that those with reduced consumption. This suggests that egg yolk consumption should be reduced or avoided in high-risk individuals with established cardiovascular disease. Consumption of a large egg (which equates to about 200 mg of dietary cholesterol) not only increases the susceptibility of low-density lipoproteins (LDL) to oxidation, but also increases postprandial lipaemia, and potentiates the adverse effects of dietary saturated fat.(5) Additionally, egg consumption effectively halves postprandial clearance of atherogenic chylomicron remnants,(6) which implies a need to re-consider egg yolk consumption in individuals with cardiometabolic disease, including those with diabetes. Indeed, in observational studies, regular egg consumption was associated with increased risk of new-onset diabetes, cardiovascular disease and all-cause mortality.(7,8) These epidemiological data, together with the FOCUS paper, provide a strong rationale for a prospective randomized trial comparing the effects of consumption of eggs or egg white-based substitutes on hard clinical outcomes.
Currently, international guidelines are inconsistent in their consideration of dietary cholesterol. There are also misconceptions that because of the efficacy of statins in lowering plasma total cholesterol and LDL cholesterol, consideration of dietary cholesterol is less relevant in statin-treated patients. Yet even with intensive statin therapy, there remains about 70% residual cardiovascular risk.(9)
Even in the absence of hard outcomes data, the R3i believes that the accumulating evidence base supports the hypothesis that egg yolk consumption represents a hidden modifiable contributor to residual vascular risk which merits re-evaluation in international guidelines.
1. Bäckhed F. Programming of host metabolism by the gut microbiota. Ann Nutr Metab 2011;58 Suppl 2:44-52.
2. Rak K, Rader DJ. The diet-microbe morbid union. Nature 2011;472:40-1.
3. Wang Z, Klipfell E, Bennett BJ et al. Gut flora metabolism of phosphatidylcholone promotes cardiovascular disease. Nature 2010;472:57-63.
4. Spence JD, Jenkins DJA, Davignon J. Egg yolk consumption and carotid plaque. Atherosclerosis 2012;224:469-73.
5. Spence JD, Jenkins DJA, Davignon J. Dietary cholesterol and egg yolks: Not for patients at risk of vascular disease. Can J Cardiol 2010;26:e336-9.
6. Cesar TB, Oliveira MR, Mesquita CH, Maranhao RC. High cholesterol intake modifies chylomicron metabolism in normolipidemic young men. J Nutr 2006;136:971-6.
7. Hu FB, Stampfer MJ, Rimm EB et al. A prospective study of egg consumption and risk of cardiovascular disease in men and women. JAMA 1999;281:1387-94.
8. Djousse L, Gaziano JM. Egg consumption in relation to cardiovascular disease and mortality: The Physician’s Health Study. Am J Clin Nutr 2008;87:964-9.
9. Cholesterol Treatment Trialists’ (CTT) Collaboration, Baigent C, Blackwell L, Emberson J et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet 2010;376:1670-81.