The inexpensive supplement L-carnitine has been found in multiple studies of patients with diabetes or fatty liver disease to greatly amplify the beneficial effects of improved diet and lipase-blocker drugs such as orlistat (Alli). It appears the supplement has low risks of side effects while significantly improving many blood test results including total cholesterol, LDL cholesterol, triglycerides, fasting blood glucose, fasting insulin, HbA1C (a marker for glycation damage to proteins used to indicate long-term glucose levels), liver function tests including AST and ALT, and inflammation tests including C-Reactive Protein and Tumor Necrosis Factor alpha.
L-Carnitine for Fatty Liver Disease Patients
One double blind study compared L-carnitine versus placebo in patients with fatty liver diseases, also known as nonalcholic steatohepatitis.
OBJECTIVES: Nonalcoholic steatohepatitis (NASH) is a known metabolic disorder of the liver. No treatment has been conclusively shown to improve NASH or prevent disease progression. The function of L-carnitine to modulate lipid proﬁle, glucose metabolism, oxidative stress, and inﬂammatory responses has been shown. The aim of this study was to evaluate the effects of L-carnitine’s supplementation on regression of NASH.
METHODS: In patients with NASH and control subjects, we randomly dispensed one 1g L-carnitine tablet after breakfast plus diet and one 1g tablet after dinner plus diet for 24 weeks or diet alone at the same dosage and regimen. We evaluated liver enzymes, lipid proﬁle, fasting plasma glucose, C-reactive protein (CRP), tumor necrosis factor (TNF)-α, homeostasis model assessment (HOMA)-IR, body mass index, and histological scores.
RESULTS: At the end of the study, L-carnitine-treated patients showed signiﬁcant improvements in the following parameters: aspartate aminotransferase (P = 0.000), alanine aminotransferase (ALT) (P = 0.000), γ-glutamyl-transpeptidase (γ-GT) (P = 0.000), total cholesterol (P = 0.000), low-density lipoprotein (LDL) (P = 0.000), high-density lipoprotein (HDL) (P = 0.000), triglycerides (P = 0.000), glucose (P = 0.000), HOMA-IR (P = 0.000), CRP (P = 0.000), TNF-α (P = 0.000), and histological scores (P = 0.000).
CONCLUSIONS: L-carnitine supplementation to diet is useful for reducing TNF-α and CRP, and for improving liver function, glucose plasma level, lipid proﬁle, HOMA-IR, and histological manifestations of NASH.
L-Carnitine for Diabetes Patients
In the double-blind placebo study for diabetes patients, Orlistat (Alli) was used to block absorption of dietary fat intake in both test groups at dosages of 120mg three time per day. One group took a placebo and the other L-carnitine at 2g once per day. The results showed that the L-carnitine supplemented group benefited from much greater improvements in many of the blood test results versus those taking only the Orlistat.
The association of orlistat plus L-carnitine was better than orlistat in improving body weight, glycemic and lipid profile, insulin resistance, and inflammatory parameters and no significant adverse events were recorded. We think that these positive effects can be due to the synergistic effects of these two drugs.
The over-the-counter weight loss drug Alli is a lower dosage version of Orlistat in 60mg capsules. One of the big obstacles for using Alli for weight loss is digestive upset complaints including excessive flatulence, oily stools, and sometimes uncontrollable defecation. This tends to be a problem for people with high-fat diets or those with little fiber in their diets. The article Losing Weight With Alli (Orlistat), Without Yellow Orange Goo discusses measures that a Alli user can take to reduce the risk of these side effects. This study of Orlistat plus L-carnitine suggests that adding L-carnitine to the program rather than using higher dosages of Alli may be a less expensive and lower risk way to achieve weight loss effects. That’s because doubling the per-meal dosage of Alli from 60mg to 120mg tends to only boost fat blocking from 25% to 30% but in doing so makes it much more likely the patient will experience digestive side effects that may make the therapy unworkable. The L-carnitine, by contrast, does not block more fat absorption but instead appears to work by helping the body to better metabolize fats as energy sources for mitochondria.
L-Carnitine Helps Increase LDL Particle Size and Lower Atherosclerosis Risk
In 2009, researchers in Italy reported that a study of 80 diabetic patients using either simvastatin or simvastatin plus L-carnitine showed that L-carnitine helps increase the size of the LDL cholesterol particles in the blood. This is beneficial to cardiovascular health because small dense LDL has a tendency to punch through the endothelial lining of blood vessels and trigger a buildup of atherosclerotic plaque as the body attempts to repair the damage. People with diabetes, the related metabolic syndrome, obesity, and fatty liver disease all have a higher risk for atherosclerotic plaque buildup, so this benefit of L-carnitine is a major bonus for them.
Therapeutic modulation of low-density lipoprotein (LDL) size could be of benefit in reducing the risk of cardiovascular events in diabetic patients. This study evaluated the efficacy of L-carnitine on the size of LDL particles in type 2 diabetes mellitus patients treated with simvastatin. Eighty diabetic patients were randomly assigned to 1 of 2 treatment groups for 3 months. The 2 groups received either simvastatin monotherapy 20 mg (n = 40) or L-carnitine 2 g/d and simvastatin 20 mg (n = 40). The following variables were assessed at baseline; after washout; and at 1, 2, and 3 months of treatment: body mass index, fasting plasma glucose, glycosylated hemoglobin, total cholesterol, LDL cholesterol, LDL subclasses, LDL size, high-density lipoprotein cholesterol, triglycerides, apolipoprotein A-1, and apolipoprotein B-100. After 12 weeks, comparing the 2 groups, we observed a decrease in fasting plasma glucose (1.45 vs 0.61 mmol/L, P < .001) and an increase in glycosylated hemoglobin (0.2% vs 0.4%, P < .05). Moreover, there was a decrease in total cholesterol (2.07 vs 1.45 mmol/L, P < .001), LDL (1.65 vs 1.29 mmol/L, P < .001), triglycerides (1.36 vs 0.41 mmol/L, P < .001), apo B-100 (49 vs 9 g/L, P < .001), and small-sized LDL proportion (10.8% vs 4.9%, P < .001), whereas LDL particle size increased (6 vs 3 A, P < .001) and HDL increased (0.2 vs 0.11 mmol/L, P < .001). We observed that patients treated with carnitine and simvastatin showed a reduction in small-sized LDL proportion and an increase in LDL particle size.
How Carnitine Works
There’s not a clear consensus to every aspect of how carnitine works in the body, but pretty much every explanation includes some mention of how it helps shuttle fatty acids into the mitochondria in each cell where they can be consumed to produce energy usable by the rest of the cell.
Without sufficient quantities of carnitine to help move fatty acids through mitochondrial membranes, the mitochondria cannot efficiently use fatty acids as fuel sources. This might explain why glucose levels and blood lipids fall when carnitine supplements are used. Consider that glucose is another fuel source for the mitochondria. If the fatty acids can’t be used well, they build up in the blood and then something else has to supply the energy. The body may adapt to this dysfunctional state by releasing glucose for the mitochondria to use as their fuel supply to make up for how they are unable to use the fatty acids.
While I have not been able to find any papers that explain the observed effects on LDL cholesterol size and am not expert enough in biochemistry to be sure about this explanation, it may have to do with the smaller fatty acids in the blood being more likely to penetrate mitochondrial membranes than larger ones when there is enough carnitine available to help shuttle them through. So if the smaller fatty acids are being used up rapidly as a fuel sources when there is adequate carnitine, you would then expect to see the proportion of small fatty acids in the blood decrease. Hopefully some intrepid researchers will investigate this further in the future to determine if it really does work this way, or if that’s already been done perhaps a reader can leave a comment to an article on this topic for further clarification.
Carnitine Improves Blood Sugar and Lipids in Diabetes
Carnitine is a small amino acid-derived molecule used by cells to shuttle fats into mitochondria, where they are burned for energy.57,58 Diabetic tissue, especially cardiac muscle, can accumulate lipids that impair function.59,60 Both aging and obesity reduce carnitine levels, contributing to mitochondrial aging and loss of metabolic control.61 That makes carnitine a very appealing supplement for its ability to promote mitochondrial health and fat/sugar utilization before problems arise.58,62
One gram of L-carnitine orally three times daily over 12 weeks significantly lowered fasting blood sugar in middle-aged adults with type 2 diabetes.
Human carnitine studies in diabetes are compelling. Given intravenously to insulin-resistant diabetics, L-carnitine or acetyl-L-carnitine improved insulin sensitivity, glucose uptake and effective utilization from the bloodstream, while improving efficiency of energy utilization.58,63 One gram of L-carnitine orally three times daily over 12 weeks significantly lowered fasting blood sugar in middle-aged adults with type 2 diabetes.64
Even if you don’t have diabetes or fatty liver disease, there may be good benefits for carnitine supplements. Consider for instance that chronic fatigue, chronic pain, and neurodegenerative disease conditions are often associated with mitochondrial dysfunction that saps the energy reserves of the body. Researchers have found that carnitine and lipoic acid supplements can help improve symptoms for all of these conditions because of the beneficial effect on the mitochondria.
Summary of Carnitine Benefits and Dosing Suggestions
Carnitine is available in several amino acid forms including the basic L-carnitine, acetyl L-carnitine, and propionyl L-carnitine. There is also a less common form known as acetyl L-carnitine arginate which is claimed to offer even more benefits for brain health, but the evidence for this is limited and it is one of the more expensive forms. There are various combinations of these forms, too. One of the most novel is the Life Extension Optimized Carnitine with Glycocarn product that combines the acetyl L-carnitine, proprionyl L-carnitine, and acetyl L-carnitine arginate forms all into one capsule.
L-carnitine is the form most often found in large skeletal muscles and the heart. Some research suggests that L-carnitine helps to improve male fertility by boosting sperm quality. L-carnitine is believed to help metabolic function throughout the body, including the muscles and brain. It also helps to build muscle mass and drop fat mass, benefits that are important for just about anybody in their 40s and older.
Probably the most widely discussed form is acetyl L-carnitine as it is thought to be somewhat better absorbed in the digestive tract and to be more beneficial for brain health and yet is generally little more expensive than L-carnitine.
While bioavailability of L-carnitine from the diet is quite high (see Dietary L-Carnitine), absorption from oral L-carnitine supplements is considerably lower. Supplemental L-carnitine is mainly absorbed by passive diffusion (1). According to one study, bioavailability of L-carnitine from oral supplements (0.5-6 gram dosage) ranges from 14%-18% of the total dose (5). Less is known regarding the metabolism of the acetylated form of L-carnitine, acetyl-L-carnitine (ALCAR); however, bioavailability of ALCAR is thought to be higher than L-carnitine. The results of in vitro experiments suggest that ALCAR is partially hydrolyzed upon intestinal absorption (10). In humans, administration of 2 grams of ALCAR per day for 50 days increased plasma ALCAR levels by 43%, suggesting that some acetyl-L-carnitine is absorbed without hydrolysis or that L-carnitine is reacetylated in the enterocyte (5).
The acetyl form is thought to be preferable for the body to make the neurotransmitter acetylcholine that is particularly important for memory. The supply of acetylcholine often dwindles in older people, possible due to a mixture of reasons such as elevated acetylcholinesterase (an enzyme that breaks down acetylcholine) and dwindling supplies of acetyl-L-carnitine.
The proprionyl L-carnitine form is often recommended for patients with intermittent claudication or vascular insufficiency as it appears to be more effective at improving blood flow, walking ability, and pain in such patients. The evidence for this form being more beneficial for its circulatory benefits appears to be significant.
There appears to be no strong data as to problems combining these forms, so you should feel free to cautiously try each form and note the differences in cost and effect for your use. L-carnitine generally is the least expensive form, acetyl L-carnitine is slightly more expensive, and proprionyl L-carnitine and acetyl L-carnitine arginate are the most expensive.
Divided dosages up to around 3g per day generally seem to have little risk of side effects. It is often recommended to take carnitine supplements by themselves apart from food to help aid in absorption, but this probably does increase the risk of digestive side effects such as cramping, bloating, diarrhea, and nausea. Generally, however, it is thought that these side effects are minimal unless a person consumes more than around 5g per day.
Some people report an energizing effects from carnitine supplements, so you should experiment and evaluate whether the supplement might keep you awake. To get started, it’s probably best to start taking carnitine supplements in the mornings after waking up and before eating breakfast. Some advise never consuming carnitine supplements past 3pm or around 6 to 8 hours before sleep. In my view, there are simply too many variables for each person to make such blanket statements. I’ve been told that some using carnitine have found that 500mg of acetyl L-carnitine at dinner or even bedtime does not impede sleep. In short, any time you use a supplement you should take some notes on your usage and effects on your sleep, energy, mood, and health so that you can better understand how that supplement affects you personally. Carnitine is no different than many other potentially energizing supplements in this regard.
I’d suggest you start with either L-carnitine or acetyl L-carnitine at 500mg once per day for a week in the mornings before breakfast to evaluate for side effects. Then try the other form at 500mg per day for a week, again looking for side effects. Then take one of each per day for a couple of weeks at which point you can start monitoring for changes in your blood test results and adjust upwards or downwards as desired. Because proprionyl L-carnitine is generally much more expensive, I’d probably only use this if intermittent claudication or vascular insufficiency are problems you are experiencing. You should be reasonably unlikely to have severe side effects if you take four to six 500mg capsules spread throughout the day in doses of no more than 1g total at a time.
I’d strongly recommend you combine carnitine supplements with some form of alpha lipoic acid (ALA). These supplements appear to work vastly better together than alone, even if you use smaller total doses to save money. For example, taking 500mg of L-carnitine with 300mg of ALA and a second dose of 500mg of acetyl L-carnitine with 300mg of ALA each day is likely going to work better overall than higher dosages of any one of these supplements. The R form of ALA is the active form, the S form is inactive. Products with more of the R form generally are more effective.
Those with neurodegenerative diseases or mitochondrial health problems is likely to especially benefit from combined carnitine plus lipoic acid supplementation. This 2008 research study out of China examined the effect in patients with Parkinson’s Disease:
Mitochondrial dysfunction and oxidative damage are highly involved in the pathogenesis of Parkinson’s disease (PD). Some mitochondrial antioxidants/nutrients that can improve mitochondrial function and/or attenuate oxidative damage have been implicated in PD therapy. However, few studies have evaluated the preventative effects of a combination of mitochondrial antioxidants/nutrients against PD, and even fewer have sought to optimize the doses of the combined agents. The present study examined the preventative effects of two mitochondrial antioxidant/nutrients, R-–lipoic acid (LA) and acetyl-L-carnitine (ALC), in a chronic rotenone-induced cellular model of PD. We demonstrated that 4-week pretreatment with LA and/or ALC effectively protected SK-N-MC human neuroblastoma cells against rotenone-induced mitochondrial dysfunction, oxidative damage and accumulation of -synuclein and ubiquitin. Most notably, we found that when combined, LA and ALC worked at 100–1000-fold lower concentrations than they did individually. We also found that pretreatment with combined LA and ALC increased mitochondrial biogenesis and decreased production of reactive oxygen species through the up-regulation of the peroxisome proliferator-activated receptor- coactivator 1 as a possible underlying mechanism. This study provides important evidence that combining mitochondrial antioxidant/nutrients at optimal doses might be an effective and safe prevention strategy for PD.
Probably the most potent form of lipoic acid around at present is the Na-RALA form which is a sodium salt combined with R form of ALA. It is also the most expensive, but not outrageously so given that its much higher bioavailability means you can use smaller doses.
There are also several formulas that combine acetyl L-carnitine and alpha lipoic acid into one capsule or tablet. These may be particularly useful for older people, those who don’t like to swallow a lot of pills, or people who want to take both supplements frequently throughout the day. A few of them also included additional ingredients beyond the carnitine and lipoic acid that should further improve benefits such as boosting energy levels and mitochondrial health.
Robert Crayhon’s “The Carnitine Miracle”
Although the studies mentioned in this article are relatively recent, carnitine has been known for much more than a decade as a nutrient offering substantial wide-ranging benefits to health. In his book The Carnitine Miracle: The Supernutrient Program That Promotes High Energy, Fat Burning, Heart Health, Brain Wellness and Longevity, author Robert Crayhon gave the general public a great deal of information on the benefits and properties of carnitine in a readily accessible form more a decade ago. A helpful and highly detailed review of this book can be found at Energy, Health and Mental Agility — The Carnitine Miracle: The Supernutrient Program that Promotes High Energy, Fat Burning, Heart Health, Brain Wellness, and Longevity by Robert Crayhon.
The Amazon reviews for this book tend to be either extremely positive or negative. Most of the reviews are strongly positive and include testimonials of major benefits from carnitine supplements including major weight loss, improved energy levels, and lowered LDL cholesterol. But there are a few very negative reviews that say carnitine didn’t help at all, generally without offering much of any detail.
My guess is that the people it didn’t help at all probably either didn’t use it at appropriate dosages for long enough time or that they have other health issues that have symptoms similar to low carnitine levels but either do not have low carnitine themselves or are also missing some other nutrient that is needed to make effective use of carnitine. That is readily possible given that weight gain, high blood lipids, and low energy can be caused by a vast number of entirely different reasons. While some possible reasons have nothing at all to do with carnitine, others are directly connected to how it is used in the body. For example, low levels of omega 3 fatty acids could impede the effectiveness of carnitine. It’s interesting to note that many studies have cited modern farmed beef products are missing most of the omega 3 fatty acids that used to be found in grass-feed beef common in the 1950s and earlier. Similar observations have been made about farm-raised fish and seafood products versus wild fish and seafood. Thus a person who eats a lot of modern farmed beef but little wild fish could find they have enough carnitine but not enough omega 3 fatty acids to help it work to its full potential and as a result, adding more carnitine isn’t going to help. It’s also possible that some people fighting obesity, diabetes, and elevated blood lipids are using statin drugs that deplete the body of CoQ10 needed for mitochondria to operate properly. Thus perhaps the readers who didn’t benefit from the carnitine needed to take more omega 3 fatty acids and CoQ10 to enable carnitine to do its job.
Carnitine Biochemisty and Food Sources
Carnitine is found in two forms, the D and L forms, just like is common for many amino acids and similar biochemicals. The L form is the active form found in foods in small quantities. Although carnitine is often called an amino acid supplement, technically it is not because it is missing a chemical component (NH2) found in amino acids. Humans can synthesize small quantities of it from from the essential amino acids lysine and methionine. In practice, this can mean that a dietary deficiency of either lysine or methionine can lead to a marked deficiency of carnitine. Common amino acid profile blood tests do not measure carnitine but do measure lysine and methionine.
Common food sources of carnitine include animal meats, particularly from sheep and cows. Dairy products such as milk, cheese, and ice cream have much lower quantities of carnitine. Fish and poultry products including meats and eggs are poor sources of carnitine, but do have some. Plants are mostly devoid of significant quantities of carnitine except for certain fatty plants such as avocados and tempeh. Even so, a medium sized avocado has only about 2mg of carnitine compared to the roughly 87mg to 99mg you would find in about a quarter pound (about 113 grams) of cooked ground beef.
According to Robert Crayhon’s book, it is thought that the diets of ancient humans that hunted probably contained 500mg or more of carnitine per day but that modern humans are often only getting 30mg to 50mg per day. The US National Institutes of Health estimates that adults eating a healthy mix of animals meats and vegetables are probably getting around 60 to 180 milligrams of carnitine per day, but vegetarians likely only get around 10 to 12 milligrams. A helpful chart showing carnitine in some common foods can be found at What foods provide carnitine?
As carnitine levels are highly variable in foods, it would take eating about one to two pounds of beef to get 500mg of carnitine. This is not practical for most people. Additionally, the high concentrates of omega-6 fatty acids in most beef and animals meats have deleterious effects on health. Thus for most people, it is probably most practical to get consistent and adequate carnitine from supplements.
Carnitine and Carnosine: Different Compounds With Some Important Similarities
Some confuse carnitine with carnosine due to the similar names. The two are chemically different as carnosine is a dipeptide formed from the amino acids beta-alanine and histidine. In actual practice, there are a number of common properties to the two distinct compounds, however. Both function as antioxidants to reduce oxidative damage to cells. There is evidence that both act to oppose aging processes, but the mechanisms are somewhat different. Carnosine is particularly well known for its ability to directly reduce glycation to proteins that occurs when sugars bind to and damage them, a process that is commonly associated with the accelerated aging involving diabetes and metabolic syndrome. Carnitine, by contrast, appears to act more indirectly on glycation by helping mitochondria to run on long chain fatty acid fuel sources and thereby making it possible for cells to have adequate energy to operate without needing elevated glucose levels that can lead to diabetes and metabolic syndrome and their accompanying rapid glycation damage.
Another important similarity between the two is that vegetarian diets tend to result in increased risk of deficiencies of both carnitine and carnosine because plants are poor sources for both. Thus vegetarians in particular are likely to benefit from supplementation with these two natural compounds. Although there are many benefits to eating a diet of mostly plant foods, the chronic lack of carnitine and carnosine are likely major reasons behind findings that vegetarians often have shorter lifespans than omnivores who eat a mix of meats and plants. For the vegetarians reading this article, I’d urge you to consider adding both carnitine and carnosine supplements to your nutritional program.
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