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Gut microbes live symbiotically within the human digestive tract and play important roles in host defense, immunity, and nutrient processing and absorption. This diverse community is unique to each person and influenced by both acute and chronic dietary exposures to various food sources.
Nutrients such as phosphatidylcholine (also known as lecithin), choline, and L-carnitine are abundant in animal-derived products such as red meat, egg yolk and full-fat dairy products. When consumed, these nutrients are processed by gut bacteria resulting in the release of various metabolites including TMA (trimethylamine) into the blood. TMA is then transported to the liver where it is converted into TMAO (trimethylamine N-oxide) which has been shown to regulate various physiological processes involved in the development of atherosclerosis.
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One of the earliest manifestations of endothelial dysfunction is nitric oxide (NO) deficiency, which promotes atherosclerosis. ADMA (asymmetric dimethylarginine) and SDMA (symmetric dimethylarginine), its structural isomer, are metabolites of L-arginine, an amino acid that is catalyzed to L-citrulline and NO by nitric oxide synthase (NOS).
Both ADMA and SDMA have distinct pathophysiologies and manifestations. ADMA is a competitive inhibitor of NOS thereby reducing NO production and promoting endothelial dysfunction. SDMA also interferes with NO production, but does so indirectly by reducing the cellular availability of arginine. ADMA is primarily cleared through enzymatic degradation in the bloodstream and identifies subclinical cardiovascular disease. Conversely, SDMA is primarily excreted in the urine and identifies reduced renal function.
Omega-3 and omega-6 fatty acids are polyunsaturated long chain fatty acids (PUFA) required by the body for proper functioning, normal growth and the formation of neural synapses and cellular membranes. Omega-3 and -6 fatty acids are considered “essential” and obtained primarily from dietary sources.
Three of the most important omega-3 fatty acids are eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA). Omega-3 fatty acids are primarily obtained from food sources, such as oily fish. They have antioxidant1, anti-inflammatory and anti-thrombotic effects, and can help to reduce triglyceride levels. Two of the most important omega-6 fatty acids are arachidonic acid (AA) and linoleic acid (LA). Omega-6 fatty acids are obtained from animal sources and plant oils, and have pro-inflammatory and pro-thrombotic properties at high levels.
The GlycoMark® test is a surrogate marker to detect frequent and high glycemic excursions in diabetic patients and measures blood levels of 1,5 anhydroglucitol (1,5-AG), a glucose-like sugar found in food.
When blood glucose levels are well controlled, most circulating 1,5-AG is reabsorbed in the kidneys instead of being excreted in the urine. In healthy individuals, circulating levels of 1,5-AG are high, with median values exceeding 20 µg/mL.
However, when blood glucose levels are high, 1,5-AG reabsorption is blocked and a majority is excreted in the urine. Blood glucose spikes of greater than 180 mg/dL result in 1,5-AG loss in the urine. Individuals with type 2 diabetes have low circulating levels of 1,5-AG2,4. Unlike HbA1c testing, which measures an individual’s average glucose over a 2-3 month period, the GlycoMark® test reveals more recent deteriorations in glucose control.
Adiponectin is an abundant hormone released by adipocytes (or fat cells), commonly referred to as an adipokine. Adiponectin plays a large metabolic role in the body, participating in the regulation of glucose levels, insulin sensitivity and lipid catabolism. Adiponectin also helps support proper endothelial functioning and has multiple anti-inflammatory properties, including inhibiting the transformation of macrophages to foam cells, one of the first steps of atherosclerosis.
Unlike other adipokines, adiponectin levels are lower in obese individuals. As adipocytes become larger with weight gain, they release less adiponectin. Among healthy individuals, women typically have higher adiponectin levels than men, and adiponectin levels tend to decrease as a person ages.
OxLDL measures protein damage due to the oxidative modification of the ApoB subunit on LDL cholesterol. The oxidation of LDL cholesterol is one of the first steps in the development of atherosclerosis. Briefly, LDL-C enters the artery wall where it becomes oxidized. OxLDL is then recognized by scavenger receptors on the macrophages which engulf OxLDL, resulting in foam cell formation, vascular inflammation and the initiation of atherosclerosis.