Carnitine is a protein that is essential to the metabolisation of fat. It is an important supplement for the ketogenic diet, although there are as yet no substantive medical studies to demonstrate the validity of this.
The importance of carnitine in the ketogenic diet
Carnitine is a protein that is essential to the metabolisation of fat. Since the ketogenic diet has reduced protein and increased fat, a carnitine supplement may be important. The role of carnitine in the ketogenic diet is not well understood; some hospitals do not recognise any need for carnitine, some prescribe carnitine only when there is a measured "deficiency" and one or two prescribe carnitine as a routine supplement. We believe carnitine should be an integral part of any ketogenic diet even though there are as yet no substantive medical studies to demonstrate the validity of this; however, carnitine is not known to have any serious adverse side effects, and anything which potentially improves the effectiveness of the diet is worthwhile.
Carnitine can operate as a laxative. Since the ketogenic diet often causes constipation, this may be a useful side effect of carnitine.
Suggestions for the use of carnitine
The following suggestions are based on our personal experience - you should discuss the situation with your neurologist, recognising the he may not be aware of the latest thinking on carnitine.
Try a carnitine supplement (at 50mg/kg/day increasing to 100mg/kg/day), and observe whether this improves the effectiveness of the diet (less fits, or better ketones). Carnitine appears to be relatively fast acting, and the benefits should be observable within a few days.
If the supplement appears beneficial, then this can be traded either as improved fit control, or as a reduction in the stringency of the ketogenic diet.
Have the carnitine levels measured on a regular basis; if the ratio is more than 0.3, then you should increase the carnitine supplement under medical supervision until an appropriate ratio is obtained (note - the normal ratio for carnitine deficiency is taken as 0.4, so the objective is to get an excess of carnitine in comparison with a "normal" level.)
Do not rely on the carnitine levels as tested as anything more than an indication. It is difficult to test carnitine levels reliably.
Sodium valproate, an anti epileptic drug available under the brand names Covulex, Depakene, Depakote, Epilim, Epival, Valproate and Valrelease, is known to cause carnitine deficiency. If it is used in conjunction with the ketogenic diet, it is important to test for carnitine deficiency.
There are other reasons why sodium valproate should be treated with caution in conjunction with the ketogenic diet. It can lead to false readings of ketone levels, and interacts with a number of other anti-epileptic drugs, including Clonazapam, Lamictal and Phenobarbitol.
Carnitine and its metabolic role
Long chain fats are metabolised by the mitochondria within the cell. Carnitine is essential to this process, because fat by itself cannot penetrate the membrane of the mitochondria. Each molecule of fat has to be transported across the mitochondrial membrane by binding with a molecule of carnitine. After the fat has been metabolised in the mitochondria, and generated the energy rich ATP, the carnitine is again required to transport the waste product out of the mitochondria as an acyl-carnitine. Carnitine was first identified in 1905, although its metabolic role only began to be understood in the 1950s.
Chemically, carnitine is a quatery amine (the same chemical family that includes choline); its full chemical name is (R)-3-carboxy-2-hydroxy-N,N,N-tri-methyl-1-propanaminium hydroxide. Carnitine come in two forms (stereo-isomers), L-carnitine and D-carnitine. Stereo-isomers have exactly the same chemical formula and structure, except that the molecules of one form are a mirror image of the other. It is only L-carnitine which is the active chemical in the metabolic process, whereas D-carnitine has no effect.
Carnitine is rapidly excreted from the body - its half life is estimated at 17 hours. This means that carnitine must be replaced continuously. In the normal human, approximately 75% of the carnitine is obtained directly as a protein in food and the remaining 25% is synthesised by the body from other proteins in food. The dietary sources richest in carnitine are red meats, particularly lamb and beef. Dairy products contain some carnitine but, with the exception of avocados, vegetables and fruit contain little or no carnitine. The dietary intake of carnitine for optimal health is unknown. An unpublished analysis of hospitalised patients in the US showed dietary intake of between 2 milligrams and 300 milligrams daily while on hospital diet.
Types of carnitine
Carnitine is available both as a prescription drug and as a food supplement from health stores. It is important to understand the differences.
A prescription drug can only be marketed with government approval. To achieve this, the drug must be proven in clinical trials, and be manufactured in an approved manner. Nutritional food supplements or health food products, on the other hand, are not subject to the same rigorous requirements. One consequence is that the prescription version is much more expensive
In the case of carnitine, there is a further difference. Carnitine comes in the two stereo-isomer forms, L-carnitine and D-carnitine. It is only the L form which is biologically active. Some health food versions of carnitine are L-carnitine, and some are a mixture of the L- and the D- forms (DL-carnitine). Because it is much easier to make, DL-carnitine is often much cheaper. There is some evidence to suggest that D-carnitine may be harmful; there may also be some safety issues with the quality of some health food carnitine relating to the imported sources of the bulk chemical. The FDA has issued an Import Alert warning about DL-carnitine. The conclusion is that you should only use the prescription drug version.
Sigma Tau is an international healthcare company with headquarters in Rome and is Italy's largest pharmaceutical company. Sigma-Tau Pharmaceuticals, the US subsidiary, is located in Gaithersburg, Maryland.
Sigma Tau, markets Carnitor® which is the prescription drug form of L-carnitine. Carnitor® is available as an oral solution, as an injection and in tablet form.
The Sigma Tau web site has a lot of information on carnitine and is well organised, although it must be remembered that it is a commercial site.
Testing for carnitine deficiency
Symptoms of severe carnitine deficiency include muscle weakness, severe confusion and angina. Carnitine deficiency is usually distinguished as primary or secondary:
Primary deficiency is caused by some underlying problem, such as the decreased natural synthesis of carnitine in the body or the altered transport of carnitine across the muscle cellular membrane.
Secondary deficiency is due to a lack of carnitine in the diet or any state that causes abnormal loss or over utilisation of carnitine.
Almost by definition, the ketogenic diet may be expected to cause a secondary deficiency in carnitine. There are low levels of protein, so there will be a lack of carnitine in the diet, while the increased intake of fat will cause an abnormal demand for carnitine.
Testing for carnitine levels is difficult. The majority of carnitine is found in muscle tissue, but it is also found in the blood, liver, and kidney. Examination of muscle tissue levels yields the more accurate results, but sampling of muscle is an invasive procedure. As a result, blood serum levels are the preferred method of diagnosis in most cases. However, since approximately 98% of total body carnitine is found in muscle and tissue, serum levels can only measure the status of the remaining 2%, and it is known that there is not necessarily a good correlation between the carnitine levels in the blood serum and in other tissues.
Most laboratories that measure carnitine levels report both free carnitine (FC ie L-carnitine available for transporting fat) and total carnitine (TC ie the L-carnitine plus acyl-carnitine, the waste product after the body has used the L-carnitine). Carnitine deficiency is defined biochemically as abnormally low plasma levels of free carnitine (FC), less than 20µM/L at age greater than one week post term. Total carnitine levels in healthy individuals range from about 30-89 µM/L. The average TC level for a healthy male is approximately 59.3 ± 11.9µM/L and in females it is approximately 51.5 ± 11.6µM/L.
To overcome the problem that the blood plasma level may be an unreliable indicator, carnitine levels are usually quoted as the ratio of the acyl carnitine (AC ie the total carnitine TC minus the free carnitine FC) to the free carnitine (FC ie the L-carnitine). That is, the carnitine ratio is (TC-FC)/FC. A ratio that is greater than 0.4 is regarded as abnormal and as an indicator of deficiency. The logic of this is simply that the higher the ratio, the greater proportion of carnitine that is being used by the body, and hence the greater the likelihood that there is a deficiency.
The levels of carnitine obtained by testing should be treated with caution. The tests are not very reliable, and there is a lack of correlation between tissue and blood serum levels. If the results of testing are not what you expect, then it may be useful to have a second test - ie if the test was a blood serum test, then try a tissue test, and conversely.
The question, then, is how all this should interpreted in relation to the ketogenic diet. There are two problems:
The carnitine level we are presumably interested in is that in the brain tissue, and this may not be well correlated with carnitine levels in other tissue, nor with blood serum carnitine levels.
Because the metabolic process is so altered in the ketogenic diet, it does not follow that the acceptable carnitine ratio is necessarily the same as with a normal diet.
It may well be that an enhanced carnitine level is advantageous, either because it facilitates the metabolism of fat, or because it compensates for some deficiency in the brain.
Since carnitine appears to be a "safe " substance - like most vitamins - it would seem sensible to ensure that there is a sufficiency within the ketogenic diet. Also, because the ketogenic diet is likely to cause a carnitine deficiency, with potentially harmful side effects in terms of muscle weakness, confusion and angina, the carnitine ratio should be tested on a regular basis.
Infants and children: The recommended dosage of carnitine is 50 to 100 mg/kg/day (equivalent to 0.5ml/kg/day Carnitor® oral solution). Higher doses should be administered only with caution and only where clinical and biochemical considerations make it seem likely that higher doses will be of benefit. Dosage should start at 50mg/kg/day, and be increased slowly up to a maximum of 3g/day (30ml/day) while assessing tolerance and therapeutic response. Monitoring should include periodic blood chemistries, vital signs, plasma carnitine concentrations, and overall clinical condition. Carnitor® oral solution may be consumed alone or dissolved in drink or other liquid food. Doses should be spaced evenly throughout the day (every three or four hours) preferable during or following meals and should be consumed slowly in order to maximise tolerance.
Adults: The recommended dosage of carnitine is 1 to 3g/day for a 50kg subject (equivalent to 10 to 30ml/day of Carnitor® oral solution). Higher doses should be administered only with caution and only where clinical and biochemical considerations make it seem likely that higher doses will be of benefit. Dosage should start at 1gm/day, (10ml/day), and be increased slowly while assessing tolerance and therapeutic response. Monitoring should include periodic blood chemistries, vital signs, plasma carnitine concentrations, and overall clinical condition.
Carnitine appears largely benign, and there are no known counterindications.
Various mild gastrointestinal complaints have been reported during the long term administration of carnitine; these include transient nausea and vomiting, abdominal cramps, and diarrhoea. Sigma Tau suggest that gastrointestinal adverse reactions with Carnitor® oral solution dissolved in liquids might be avoided by a slow consumption of the solution or by a greater dilution.
Dosage with carnitine may also cause a fishy breath odour. This is caused by excess growth of intestinal flora promoted by carnitine in the gut. The odour may be reduced by increasing the bedtime dose and by spreading the other carnitine doses more regularly through the day. Diminishing the carnitine dose should also eliminate the odour, but it may be better to treat with a broad based antibiotic, so that the carnitine level can be maintained.
It is reported that DL-carnitine, which is sometime sold as a nutritional supplement, has been shown to cause a myasthenia (muscle weakness) type syndrome in some patients. This side effect has not been seen with the L-carnitine form, which is the prescription drug.
Other benefits of carnitine
Carnitine is one of the wonder biochemicals of the nineties, and is being recommended as a treatment for many things.
There are a few groups at particular risk of carnitine deficiency, these include chronic kidney failure patients on hemodialysis and patients with liver failure. Even some healthy subgroups may have additional needs for dietary carnitine. These include strict vegetarians, new-borns, pregnant women and women who are nursing infants.
Research suggests a potentially important role for L-carnitine in the treatment and possibly the prevention of some forms of cardiovascular disease. It was reported some time ago that supplemental carnitine can significantly reduce total blood lipids and derivatives (fats and fat like substances), a finding confirmed in recent years by Japanese researchers who reported that giving 900 milligrams per day of oral L-carnitine could notably reduce levels of blood triglycerides, which are among the lipids and derivatives implicated in cardiovascular disease.
Carnitine in the form of acetyl-L-carnitine is also being used as a treatment for Alzheimer’s disease. Acetyl-L-carnitine affects the cholinergic system, the dopaminergic and NMDA receptor systems; all these affect brain activity.
Like MCT oil, carnitine is being touted as a wonder additive by health food stores. Among the many claims for carnitine are that it reduces heart disease, promotes intelligence, slows the ageing process and can be used as a dieting agent. It is also being used as a supplement by athletes to enhance performance, on the basis that it promotes the metabolism of fat, and improves the efficiency of muscles.
Abstracts of recent papers on carnitine
return to Supplements for the ketogenic diet
(update 1.1: 18 July 2002)
(issue 1: 20 February 2000)