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L-Carnitine: A Fat-Loss Myth or Supplement Staple?

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L-Carnitine: A Fat-Loss Myth or Supplement Staple?

Is L Carnitine a fat loss myth or a supplement staple? Find out what science has to say about the benefits of L-Carnitine supplementation in this article.
Sometimes there is a chemical so central to a process in human physiology that it would defy logic that supplementing the amount or function of the molecule should do anything other than make our health better.

Certainly, the example of creatine monohydrate and the benefits of creatine supplementation on not only muscle mass and strength, but also bone density, neurological function, and other vital processes is an obvious demonstration.

Insofar as fat loss is considered, a number of key molecules have been investigated, such as ketones, beta-2 and beta-3 agonists, specific fatty acids, monoacylglycerides and diacylglycerides, and various hormones.

Yet, in the process of transporting free fatty acids from the cytosol (insides) of a cell to the mitochondria where fatty acids are “burned” to generate energy (ATP) and heat, there is one key molecule— L-carnitine.1

L-carnitine acts like the hostess at a restaurant, escorting you to your table.

Free fatty acids are either taken up from the bloodstream or released from fat stores in metabolically active cells (e.g., skeletal muscle, heart) into the cytosol (cell’s “insides”).

In the absence of L-carnitine, the fatty acids would pretty much stand around or get converted into stored fat.

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It is similar to walking into a restaurant when the hostess is on break— you end up standing around in clusters, while some wander to a random table or just leave without “fueling up.”

For purists, L-carnitine’s action relative to beta-oxidation occurs between the outer and inner mitochondrial membrane, but let’s keep it simple for clarity’s sake.

The Need for Carnitine
Much like creatine, L-carnitine can be made in many tissues, so healthy people tend to have “enough” L-carnitine. As the “L” form suggests, carnitine is an amino acid, so the body is able to convert precursor amino acids (L-lysine and L-methionine) to L-carnitine in the kidney, liver, and brain.

However, there are recognized cases of carnitine deficiency. Also, endogenous (in the body) production can only produce a limited amount, so the diet is the primary source of L-carnitine in omnivores, sourced primarily from meat; red meat has the highest concentration, with poultry and fish containing much less.

Vegans are nearly dependent upon endogenous production, accounting for 90 percent of their total L-carnitine. This sounds very similar to creatine’s story, if you are familiar with that. Also, when L-carnitine supplies are low, the kidneys will work harder to pull back any that spills into urine so it is not excreted.1

Why Supplement L-carnitine?
So, is there any need to supplement L-carnitine? Certainly, there are people who have been identified with L-carnitine deficiency, often due to transporter issues (difficulty getting L-carnitine into cells, or absorbing it from the diet).2

Additionally, newborns and infants may have a greater need for L-carnitine. But what about athletes, or healthy adults looking to lose fat? Initially, the answer appears to be “no.”3 Certainly, L-carnitine has not made a splash as a stand-alone product in the supplement market; it is not a banned substance; and there aren’t even any celebrity endorsers.

Numerous studies have shown conflicting results, with many showing no added benefit from supplementing L-carnitine during a dieting phase.

Before tossing out L-carnitine, consider whether the studies have looked at conditions that might be relevant to athletes or specific diets. Could it be similar to creatine, where strength gains are not so spectacular in sedentary people, so L-carnitine would require an increase in fatty acid oxidation or impaired absorption?

L-carnitine has had a positive effect when used in combination with certain drugs. Sibutramine, a drug no longer available on the market, was an effective weight-loss drug with metabolism-boosting effects and also acted as an appetite suppressant; its structure shares features with amphetamine.

In a yearlong study, subjects given L-carnitine (2 grams per day) in addition to sibutramine lost approximately four more pounds over the course of a year, compared to those given only sibutramine.4 Additionally, fat cell-derived hormones called adipokines— leptin and adiponectin— changed consistent with better metabolic health.

Another one-year study using L-carnitine, this time in association with the drug (now over-the-counter) Alli (orlistat) also showed not only great fat loss (again, about four pounds more), but also signs of better insulin sensitivity and reduced inflammation.5

Orlistat blocks the digestion and absorption of dietary fat, which may reduce the absorption of L-carnitine from the gut. It is also possible that the reduced calories absorbed with orlistat may make the body more dependent on using stored fat. Regardless, these two studies (lasting one year) both showed similar results.

So, does L-carnitine work for fat loss? It may, but it doesn’t seem to be quick, and may be dependent on other conditions for a relevant effect in these examples.

Health Benefits
L-carnitine is not just a weight-loss supplement— it also has been shown to have benefits in lowering blood sugar and improving the cholesterol profile in type 2 diabetics.6 In fact, there is a litany of health conditions where L-carnitine could or has shown to offer benefits.

Peripheral vascular disease, erectile dysfunction, cardiovascular disease, dementia and memory issues, kidney disease and exercise performance are all areas where L-carnitine holds potential as a therapeutic agent.7

Diets in most L-carnitine studies have focused primarily on calorie restriction, but what about low-carb diets? An extreme example is the ketogenic diet, such as that prescribed for children with epilepsy and maintained for decades. Certain medications can interfere with L-carnitine’s production or excretion, making a deficiency more likely.

Further, the exaggeratedly high concentration of fatty acids and ketones produced with this diet are capable of raising the “acyl- versus free” L-carnitine ratio. This is a rough measure of the adequacy of L-carnitine in the mitochondria, and when the ratio becomes too high, it suggests that the body is not capable of handling the demands of all the fat being used for calorie burning.

Though it is not universal, a fair percentage of those on a ketogenic diet become L-carnitine deficient (absolute or relative), and demonstrate better control of epileptic events, as well as respond better to medication when supplemented with L-carnitine.8

In calorie-restricted diets, the value of L-carnitine is less certain. However, commonly reported consequences of low-fat diets are fatigue and poor appetite control. In fact, it appears that lowering fatty acid oxidation may contribute to overeating.9

One possible solution to try may be to ensure that fatty acid oxidation (calorie burning) is optimized by supplementing L-carnitine, as many of the dietary sources of L-carnitine may not be appropriate food choices for a low-fat diet.

A study of individuals with metabolic syndrome comparing L-carnitine-supplemented subjects (where L-carnitine was administered intravenously) to a control group showed that L-carnitine reduced hunger and fatigue, as well as improved weight loss and metabolic changes, during very low-calorie dieting.10

Is it possible that even healthy people may be deficient without cause or symptoms? Well, though it seems a stretch, in a screening study looking for genetic anomalies in healthy adult volunteers, L-carnitine deficiency was detected and a genetic cause was determined.11

There was only one case, but this was out of a group of only 80 subjects. In addition to low L-carnitine (due to a heterozygote transporter mutation), elevated 3-methylhistidine was present, suggesting elevated muscle breakdown.

Again, all volunteers were initially screened and found to be healthy and without symptoms, by standard exams. This individual would likely be offered treatment similar to symptomatic L-carnitine deficiency cases, that being L-carnitine supplementation.

So, L-carnitine probably helps with weight loss, just not quickly or by itself. It has other health benefits, perhaps better expressed when consumed as acetyl-L-carnitine or propionyl-L-carnitine. Perhaps it even aids in athletic performance, especially when training increases the stimulus for increased or prolonged fatty acid oxidation.12

Unfortunately, best results require combining a considerable (~80 grams) load of carbohydrates to “push” the L-carnitine into the skeletal muscle and increase muscle stores, as well as increasing energy expenditure.13

Adverse Effects
Unfortunately, all is not rosy with L-carnitine. During the last decade, reports have arisen of a metabolite produced by gut bacteria digesting L-carnitine (and choline) called TMA. TMA is further metabolized into a chemical called TMAO (trimethylamine N-oxide) and circulates through the bloodstream.14

Researchers looking for a link between red meat-based diets and cardiovascular disease discovered that high levels of TMAO were associated with a higher risk of cardiovascular disease. Other studies suggested a link to kidney failure, diabetes, and certain cancers.

Suddenly, a cloud looms over the fate of L-carnitine. However, it is also known that TMAO is also present in high concentration in seafood, which is associated with a positive (beneficial) cardiovascular effect. Further, though TMAO may be involved in harmful processes, it is also involved in protective functions.

Steak and Seafood are a good source of l carnitine

Clearly, there is much to be learned about this simple molecule.

So, what is a person to do? L-carnitine is present in the diet, and produced by the body, and its controversial metabolite has beneficial as well as potentially adverse effects. The conversion of L-carnitine and choline to TMAO happens in the gut bacteria.

Some are exploring the various bacteria present in the gut to see if probiotics may reduce the TMAO conversion. Patients with deficiency of L-carnitine production or transport are treated lifelong with high-dose supplementation.

Unfortunately, no one has reported on the cardiovascular health of this group. It is too cloudy to give a firm recommendation for or against L-carnitine supplementation. Its benefits are likely slow and require another agent working alongside for weight loss, and the athletic benefit is not conclusively proven.

However, there is promise, as well as health benefits for important organs such as the heart and brain. If consuming L-carnitine, it would be wise to limit the daily intake to that used in studies (4 grams per day or less). Further, it will reduce the amount that reaches the gut bacteria if it is taken in divided doses of one gram.


References
Reuter SE, Evans AM. Carnitine and acylcarnitines: pharmacokinetic, pharmacological and clinical aspects. Clin Pharmacokinet 2012;51:553-72.
Magoulas PL, El-Hattab AW. Systemic primary carnitine deficiency: an overview of clinical manifestations, diagnosis, and management. Orphanet J Rare Dis 2012 Sep 18;7:68(6 pp). doi: 10.1186/1750-1172-7-68.
Brass EP. Carnitine and sports medicine: use or abuse? Ann NY Acad Sci 2004;1033:67-78.
Derosa G, Maffioli P, et al. Effects of combination of sibutramine and L-carnitine compared with sibutramine monotherapy on inflammatory parameters in diabetic patients. Metabolism 2011;60:421-9.
Derosa G, Maffioli P, et al. Orlistat and L-carnitine compared to orlistat alone on insulin resistance in obese diabetic patients. Endocr J 2010;57:777-86.
Vidal-Casariego A, Burgos-Peláez R, et al. Metabolic effects of L-carnitine on type 2 diabetes mellitus: systematic review and meta-analysis. Exp Clin Endocrinol Diabetes 2013;121:234-8.
University of Maryland Medical Center. Carnitine (L-carnitine). https://umm.edu/health/medical/altmed/supplement/carnitine-lcarnitine, accessed August 31, 2015.
Neal EG, Zupec-Kania B, et al. Carnitine, nutritional supplementation and discontinuation of ketogenic diet therapies. Epilepsy Res. 2012 Jul;100(3):267-71.
Leonhardt M, Langhans W. Fatty acid oxidation and control of food intake. Physiol Behav 2004;83:645-51.
Zhang JJ, Wu ZB, et al. L-carnitine ameliorated fasting-induced fatigue, hunger, and metabolic abnormalities in patients with metabolic syndrome: a randomized controlled study. Nutr J 2014 Nov 26;13:110(11 pp). doi: 10.1186/1475-2891-13-110.
Guo L, Milburn MV, et al. Plasma metabolomic profiles enhance precision medicine for volunteers of normal health. Proc Natl Acad Sci USA 2015 Aug 17. [Epub, ahead of print]
Huang A, Owen K. Role of supplementary L-carnitine in exercise and exercise recovery. Med Sport Sci 2012;59:135-42.
Stephens FB, Wall BT, et al. Skeletal muscle carnitine loading increases energy expenditure, modulates fuel metabolism gene networks and prevents body fat accumulation in humans. J Physiol 2013;591:4655-66.
Ufnal M, Zadlo A, et al. TMAO: A small molecule of great expectations. Nutrition 2015 Jun 1. [Epub, ahead of print]
 
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