Atherosclerosis And Cardiovascular Disease
There are many nutritional preparations and supplements that have been studied in the context of cardiovascular disease. Here, we summarize the evidence for many of these supplements. The order in which the categories are listed in this Protocol is alphabetical. However, the lists of nutrients within each category are generally organized with those nutrients or supplements with the best evidence at the top of each list. Coenzyme Q10 (CoQ10) is a naturally occurring lipid-soluble antioxidant that plays an important role in cellular energy metabolism. A randomized placebo-controlled trial with 443 healthy, elderly, Swedish participants found 200 mg CoQ10 plus 200 mcg selenium daily for five years reduced cardiovascular mortality.12 The effect persisted at a 12-year follow-up, at which time 38.7% of those in the placebo group and 28.1% of those in the supplement group had died from cardiovascular causes. Analyses of the data showed patients with hypertension, diabetes, heart disease, and impaired functional capacity all benefited from CoQ10 plus selenium therapy.404 Several secondary studies based on data from this trial suggest mechanisms such as reduced oxidative stress, inflammation, and glycation405-407; improved cellular metabolism; and improvement in markers of aging408,409 may be partly responsible.
L-arginine, a conditionally essential amino acid found in protein-rich foods, has attracted attention for its ability to improve endothelial function and dilate blood vessels. L-arginine serves as a precursor for NO in the endothelium.410 It also enhances mitochondrial function, lowers oxidative stress, and reduces oxidized LDL levels.411,412 Multiple clinical trials have indicated L-arginine supplementation may have beneficial effects on blood pressure, GlycoMode metabolic wellness endothelial and microvascular function, glucose metabolism, insulin sensitivity, lipid profiles, and body weight and composition.410,413 However, findings have been inconsistent.411,412 In a meta-analysis of 22 randomized controlled trials involving a total of more than 1,100 subjects, L-arginine supplementation, at doses of 4 grams per day or higher for at least 24 weeks, was found to reduce systolic and diastolic blood pressures, with no additional benefit from doses higher than 9 grams per day. Lipoic acid, a naturally occurring antioxidant, serves as a coenzyme in metabolism of fats, carbohydrates, and proteins.
It can restore radical-scavenging capacity to other antioxidants like thioredoxin (an antioxidant protein), vitamin C, and glutathione, which in turn can recycle vitamin E. Lipoic acid also helps manage proper serum glucose levels in diabetic patients. Lipoic acid may be beneficial in individuals with conditions that increase cardiovascular risk. Propionyl-L-carnitine is a naturally produced derivative of L-carnitine that rapidly passes into cells to supply free L-carnitine, a much-needed factor for mitochondrial energy production. Clinical trials indicate propionyl-L-carnitine may relieve symptoms in individuals with peripheral artery disease. A large review examined findings from 12 randomized controlled trials with a combined total of 1,423 participants. The accumulated evidence showed propionyl-L-carnitine, at doses of 1-2 grams per day, increased maximum and pain-free walking distances by 26% and 31%, respectively, in those with intermittent claudication (pain while walking due to atherosclerosis in the legs) relative to placebo. Known best as supplements for combating osteoarthritis and joint pain, glucosamine and chondroitin may have benefits beyond these indications.
A growing body of observational evidence suggests glucosamine and chondroitin may have cardio-protective effects. Findings from a study that included data collected over a median of 8.9 years from 495,077 participants in the United Kingdom’s health resource databank (UK Biobank) suggested people taking glucosamine supplements for arthritis had a lower risk of death from cardiovascular disease, atherosclerosis, and heart attack and stroke.427 A previous study using the same database found glucosamine users were less likely to develop coronary artery disease or have a major cardiovascular event or stroke during seven years of monitoring.428 Chondroitin use was found in another study to be associated with 52% lower odds of heart attack during a 13-year period in people at high cardiovascular risk.429 Another observational study that used data from 38,021 adults in the United States who were followed for 15 years found that the use of glucosamine and chondroitin supplements was associated with a trend towards decreased cardiovascular mortality, but it did not reach statistical significance.430 Further rigorous investigations are necessary to elucidate the effects of glucosamine and chondroitin on cardiovascular health.
A meta-analysis of data from 17 randomized controlled trials investigating the effects of tomato or lycopene interventions on cardiovascular risk factors showed supplementing with tomato lowered LDL-cholesterol levels and improved endothelial function (measured as flow-mediated dilation), and lycopene supplementation reduced systolic blood pressure.437 For example, in a randomized placebo-controlled trial involving 36 patients with stable cardiovascular disease, adding 7 mg per day of lycopene to statin therapy for two months led to improved endothelial function.438 In another randomized controlled trial, 144 middle-aged participants were assigned to receive 20 mg lutein (another carotenoid), 20 mg lutein plus 20 mg lycopene, or placebo daily for eight weeks. Fish oil is rich in omega-3 polyunsaturated fatty acids (PUFAs), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). These omega-3 PUFAs work in part by suppressing inflammation, the main driver of atherosclerosis.243 One way they do this is through the action of derivatives known as specialized pro-resolving mediators, or SPMs. A number of controlled trials and meta-analyses have examined the potential role of omega-3 PUFA supplementation in cardiovascular disease prevention.