A recent investigational study published by Koeth et al. in the journal Nature Medicine1 examined levels of a compound called trimethylamine-N-oxide (TMAO) in relationship to microbial metabolism of carnitine in the gut. The researchers cite very recent, limited research suggesting TMAO may be a risk factor for cardiovascular disease. They then provocatively propose that carnitine consumption may increase cardiovascular risk in some individuals due to increasing TMAO levels following microbial metabolism of the compound.
The authors report the intestinal bacterial flora of people who consume red meat, a source of dietary carnitine, was conducive to TMAO production in the presence of carnitine, whereas vegetarians produced little to no TMAO under the same circumstances. They concluded that alterations in the intestinal microbiota associated with meat consumption may promote the formation of TMAO from dietary carnitine, and therefore suggested that the carnitine content of red meat may be one of the reasons it is linked to heart disease.
Following publication of this study, mainstream media outlets propagated misleading headlines blaming carnitine for heart disease without explaining that these findings were very preliminary and that red meat consumption was required for the observed effect. Life Extension® members are well aware of the potential health threats associated with red meat consumption, such as exposure to saturated fats and advanced glycation end products,4 and many already consume a heart-healthy, plant-based diet such as the Mediterranean diet.
These deceptive media headlines have generated concern that supplemental forms of L-carnitine may be detrimental to heart health. This notion flies in the face of numerous published, peer-reviewed studies showing L-carnitine promotes cardiovascular health in a variety of ways. The media's effort to generate headlines has undermined decades of scientific research on the heart-health benefits of carnitine.
Ironically, days after publication of the Koethe et al. carnitine article, a new meta-analysis of the research on carnitine and heart health was published by researchers from Mayo Clinic. This large systematic review provides strong evidence for carnitine's benefits in heart health. This article examined 13 controlled trials that enrolled, collectively, 3629 participants, representing the largest, most powerful scientific review of carnitine's cardiovascular benefits to date.2
The authors of the Mayo Clinic study found carnitine supplementation was associated with a 27% reduction in all-cause mortality, a 65% reduction in ventricular arrhythmias, and a 40% reduction in angina symptoms in patients who had experienced a heart attack. These effects were thought to occur through multiple mechanisms, including improved energy metabolism in the mitochondria, decreased ischemia, and enhanced left ventricle function.2
The authors describe carnitine as an inexpensive therapy with an "excellent safety profile" which could potentially be used in patients with angina or who are at risk for angina after suffering from a heart attack. Based on the results of this meta-analysis, the authors suggest L-carnitine as a potential future therapy for heart attack and secondary coronary prevention and treatment, including angina. The scientists state: "Further study with large randomized controlled trials of this inexpensive and safe therapy in the modern era is warranted." Unfortunately they also note: "However, a large trial may never be performed because L-carnitine is an over-the-counter supplement available to the public, which decreases the potential revenue compared with a synthesized [pharmaceutical] product."2
Carnitine's benefits are well-established and Life Extension® has written about them at length over the years. The next several paragraphs describe some of the key health benefits associated with carnitine.
The heart muscle uses fat as its primary energy source. Carnitine is a fat-transporting compound that is absolutely essential for normal heart function.5 Over time, the decline of carnitine plays a role in the weakening of the heart's muscles.6
People with heart muscle damage due to heart attacks or heart failure have especially low carnitine levels.7-9 Fortunately, carnitine supplementation has proven to be remarkably effective in fighting and even reversing the heart-weakening effects of that drop in carnitine levels.6
In one study, 160 male and female heart attack survivors between 39 and 86 years old received either 4 grams/day of L-carnitine or a placebo for 12 months.10 The patients taking L-carnitine experienced significantly favorable decreases in heart rate and blood pressure; they also had improved blood lipid profiles. Most importantly, those supplementing with carnitine had a dramatically reduced death rate compared to those not taking carnitine. Patients taking carnitine had a death rate of just 1.2% in the entire year, while 12.5% of control patients died, with the majority of deaths attributed to repeat heart attacks.10
L-carnitine supplementation also prevents the progression of heart muscle damage in people with congestive heart failure and improves exercise tolerance in people who develop chest pain (angina) with exertion.7 In one study, 55% of patients experienced improvement in their standard heart failure classification.7
People with angina, an early sign of impaired blood flow (ischemia) to the heart muscle, benefited from carnitine supplements. A natural carnitine derivative (propionyl-L-carnitine), at a dose of 500 mg, 3 times daily, increased the average time patients could exercise without EKG signs of ischemia by an impressive 450%.17 That result indicated improved blood flow to heart muscle cells following ischemia, an effect amply demonstrated in animal studies.11,12
Carnitine also increases concentrations of nitric oxide, which helps endothelial cells relax and increase blood flow, an effect that can help lower blood pressure.13-15 Three weeks of supplementation with 2 grams of L-carnitine improved blood flow by 17% during the critical after-meal period in a group of people fed a high-fat meal; placebo patients had a 12% decrease in blood flow.16 And a daily 6-gram intravenous dose of propionyl-L-carnitine for one week improved walking distance in people with peripheral arterial disease by 28%.17
As obesity rates skyrocket, more and more Americans are developing type II diabetes as a result, producing a syndrome called "diabesity."18,19
Since carnitine helps the mitochondria utilize energy, it plays a critical role in reducing the occurrence and impact of diabesity.20 Recent studies show that in addition to helping the mitochondria burn fat as energy, carnitine is also vital for removing waste products from mitochondria.21,22 This is important because we now recognize that the buildup of mitochondrial waste products is one of the most important contributors to insulin resistance, which further promotes high blood sugar and obesity.23
Obesity and aging contribute to low carnitine levels, which compromises mitochondrial performance and increases insulin resistance, promoting further obesity and carnitine reduction. Restoring carnitine levels to their youthful values is an effective way to break this deadly cycle.21
Human volunteers who took L-carnitine 3 grams/day for 10 days had favorable changes in body composition.24 Supplemented patients used their fat for energy, burning it 22% faster than control patients, without any increase in muscle protein breakdown. In another study, using 2 grams/day for 6 months, demonstrated a loss of total fat mass of 4 pounds, with a gain in lean muscle mass of 8.4 pounds.25
Animal studies confirm and extend these findings, showing that propionyl-L-carnitine decreases body weight gain, food intake, and fat composition while improving insulin resistance.20
Carnitine also has multiple favorable effects on elevated blood sugar and insulin resistance, the hallmarks of type II diabetes.22 Animals fed a high fat diet develop the same symptoms and signs that humans do: obesity, insulin resistance, abnormal lipid profiles, and liver damage, which are known as metabolic syndrome. Just 4 weeks of treatment with L-carnitine reversed all of those abnormal parameters.18,26-28
Similar effects have been found in diabetic humans. Two grams of L-carnitine twice daily for 10 days improved insulin sensitivity and reduced insulin levels.29 L-carnitine supplementation of two grams/day caused a significant reduction in plasma free fatty acids, which contribute to insulin resistance.30 Three grams/day were shown to reduce simulated after-meal blood sugar spikes from 157 mg/dL to 132 mg/dL (oral glucose tolerance test).31 A significant number of studies document the deadly impact of elevated after-meal glucose levels.
Research suggests that a specific form of carnitine, called propionyl-L-carnitine (PLC), plays an important role in protecting the function and health of endothelial cells.32-34 Studies also indicate that PLC may act as a nutritional corrective agent, relieving clinical symptoms of cardiovascular conditions such as peripheral arterial disease, angina, coronary artery disease, cardiomyopathy, intermittent claudication, ischemic heart disease, atherosclerosis, and congestive heart failure.35-42 PLC appears to be more potent than L-carnitine in improving vascular function.43
PLC passes across the mitochondrial membrane to supply L-carnitine directly to the mitochondria, the energy-producing organelles of all cells. This is important because heart muscle cells and endothelial cells burn fatty acids rather than glucose for 70% of their energy. By contrast, most cells generate 70% of their energy from glucose and only 30% from fatty acids.44
Carnitine deficiency has been associated with congestive heart failure.51 PLC supplementation has been reported to increase exercise capacity, optimize energy production, and reduce ventricular size in patients with congestive heart failure.38
The myocardium, the muscular substance of the heart, comprises cells called cardiomyocytes. A study of cardiomyocytes found that PLC helped to correct an imbalance between the production and utilization of adenosine triphosphate (ATP), the energy currency used throughout the body. This suggests that PLC may improve cardiac performance by improving energy metabolism and optimizing ATP levels.45
An animal study suggests PLC may help to prevent or decrease the severity of atherosclerosis. In rabbits fed a high-cholesterol diet, which normally induces endothelial dysfunction and subsequent atherosclerosis, supplementation with PLC resulted in reduced plaque thickness, markedly lower triglyceride levels, and reduced proliferation of foam cells, thereby preventing the progression of atherosclerosis.41
PLC has been shown to have a protective role against vascular cell inflammation that other carnitines do not. When rodents were exposed to irritating chemicals, PLC protected their vascular cells from this source of damage, but L-carnitine and acetyl-L-carnitine did not, leading the study authors to support "a specific protective role of PLC in the vascular component of the inflammatory process."33
PLC improves endothelial function by increasing nitric oxide production in animals with normal blood pressure and in animal models of hypertension. The increased nitric oxide production induced by PLC is related to its antioxidant properties; PLC reduces reactive oxygen species and increases nitric oxide production in the endothelium in the presence of superoxide dismutase (SOD) and catalase.46
Oxygen-deprived endothelial cells produce large amounts of free radicals. Laboratory findings suggest that PLC protects these cells during periods of oxygen deprivation. When blood flow is restored, PLC also allows the cells to regain their lost energy charge much faster.34
An animal study indicates that PLC prevents abnormal heart muscle function associated with diabetes. The researchers found that PLC significantly increased both fatty acid and glucose utilization while restoring cardiac muscle function. These findings suggest PLC prevents diminished cardiac function associated with diabetes, possibly by promoting a favorable shift in glucose and fatty acid metabolism.47
The totality of these numerous studies contradicts the report that carnitine in red meat diets increases atherosclerosis risk.
As part of a thorough evaluation of this issue, Life Extension's Health Advisors spoke to a representative sample of 115 customers who supplement with carnitine and inquired as to their experience with the compound. Not surprisingly, not one member reported having a cardiovascular event such as a heart attack or stroke after initiation of carnitine supplementation. On the contrary, many customers reported their cardiovascular health improved after they started supplementing with carnitine. Although there are limitations to anecdotal reports, actual Life Extension customers using carnitine for health purposes nevertheless reported a variety of benefits (full names not disclosed for confidentiality purposes):
Despite the media attention given to the study published in Nature Medicine by Koeth et al., caution must be used when applying the results to cardiovascular risk. Life Extension® has carefully examined this study and identified the following factors with this study that are summarized below.
For more information about carnitine or free guidance on a health regimen that is right for you, please contact a Life Extension® Health Advisor at 1-800-226-2370.
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