Some of you have been doing a ketogenic diet for a while. And some of you haven’t. And regardless of how long you have been doing your ketogenic diet, you may not have had very good ketone levels or may have of had higher ketones in the beginning and watched them plummet or become inconsistent without a reason you could figure out. And when you asked about it in forums and watched YouTube videos to learn why, the general consensus was something like, “You are just better (more) fat adapted. You are absorbing them better for fuel, and so there is less in the bloodstream to test. If you feel good, don’t worry about it.”

And that certainly may be the case. But something else might be going on that you need to be aware of, and it’s not something you will want to just ignore. Because ignoring it may have some longer-term health effects that I want you to be aware of and has nothing to do with what some people call “chasing ketones.”

The term “chasing ketones” comes from the low-carb world in general, in which people may not be using ketogenic diets primarily for psychiatric illness or neurological disorders. And don’t get me wrong, not everyone needs or wants to have higher ketone levels, and there are people who get wonderful and sustained psychiatric and neurological treatment effects without higher ketone levels that we would generally describe as therapeutic levels.

But for conditions in which higher levels may create better therapeutic outcomes, it does not make sense to not investigate a well-known reason they can go down, or just become inconsistent. I assure you, it is not always just a case of your body utilizing them more efficiently. Sometimes your body just can’t make them well anymore. Even though you have not changed a thing, and maybe you have nailed your ketogenic diet, and your dietician or nutritionist is telling you that you are doing everything right.

Enter a very important supplement well-known in the epilepsy world called L-Carnitine. Where carnitine depletion is carefully watched for and monitored. Why? Because in order for the fat you are burning off your body or the fat you are eating to turn into an actual ketone body, it has to be shuttled into a mitochondrial membrane. And that shuttle is carnitine-dependent.

Carnitine is an amino acid found in red meat. Carne means red in Latin. So it’s easy to remember the best sources to find it. But here is the thing. Even if you are eating what you would consider a lot of meat, you can run low. Meaning, if you have a lot of fatty acids to burn and make into energy sustaining ketone bodies for brain healing, your body may use up it’s stores of carnitine. And if you were vegan or vegetarian before (or even during) your ketogenic diet and avoiding red meat it is really something that needs to be assessed carefully before the construction of the diet and it’s management.

Luckily, your body can make some of its own carnitine from the amino acids lysine and methionine. Lysine gets methylated to form trimethyllysine (TML) using a methyl group from methionine. Through several enzymatic steps, with co-factors like vitamin C and B6, carnitine is produced. Notice that there are micronutrients involved in the construction of additional carnitine (so you have to be replete or at least not deficient or insufficient in these nutrients).

And pay attention when I tell you that lysine and methionine are essential amino acids, meaning they must come from the diet for biosynthesis to occur. So once again, we need to make sure that our vegan and vegetarian friends are getting adequate protein that is successfully being broken down into amino acids, and that the protein composition of their diet includes these important essential amino acids in sufficient amounts. But carnitine itself is not strictly essential, because once you have enough lysine, methionine, and the needed cofactors (vitamin C, iron, vitamin B6, niacin), your body can synthesize carnitine on its own. And that’s great! But you can still become insufficient or even deficient in carnitine while rocking your ketogenic diet.

You may think it takes really a long time to become depleted in carnitine. Or that it only happens in vegans and vegetarians. Or that it only happens in those hard-core, more restrictive ketogenic diet formulations like a 4:1 or 3:1 ratio like they give the kiddos with epilepsy.

And while those are logical assumptions, I can tell you confidently that is not the case in my experience in this field. And it is also documented in the research literature.

Our study revealed that 38.3% of adult patients with epilepsy following MAD [Modified Atkins Diet] experienced low free carnitine at some point through the course of diet therapy. 

Chu, D. Y., Ravelli, M. N., Faltersack, K. M., Woods, A. L., Almane, D., Li, Z., … & Felton, E. A. (2024). Hypocarnitinemia and its effect on seizure control in adult patients with intractable epilepsy on the modified Atkins diet. Frontiers in Nutrition, 10, 1304209.

And that occurred on a Modified Atkins Diet (MAD) which is considered one of the easiest and least restrictive forms of ketogenic diets, without limits on protein consumption. This unrestricted protein consumption should have insured a nice sufficient supply of carnitine for ketone production, assuming a diet with at least some red meat. But what was very important to note was that the people in the study who developed hypocarnitinemia (low carnitine levels) had more seizures than those who did not. And so I would wonder, or perhaps even be so bold as to argue, that if you are using a ketogenic diet for mental illness, you may also have poorly controlled symptoms as ketone levels go down due to insufficient carnitine availability. And in this study, people saw those carnitine levels start to go down in as little as a month.

Did your ketone levels go down and you started supplementing more MCT oil to get them back up? You may be masking a problem. In the liver, medium-chain fatty acids cross mitochondrial membranes independently of carnitine. Beta-oxidation produces acetyl-CoA, which fuels ketogenesis, leading to ketone bodies like acetoacetate and beta-hydroxybutyrate. Carnitine isn’t required for MCT oxidation or ketone production, even in its deficiency. So just because you make ketones on your MCT oil and those levels are measured in the blood, it doesn’t mean that you are not carnitine insufficient. You are relying on an exogenous ketone source with MCT. Not an endogenous one coming from your own production as we expect to be seen with sufficient carnitine levels.

Don’t care about your ketone levels? That’s cool. But you should care about your carnitine status. And I am going to tell you why. First we need to talk about the differences between a primary carnitine deficiency and a secondary carnitine deficiency. A primary one is genetic, and you would know about it a long time ago. You would not be rocking your ketogenic diet if you had a primary carnitine deficiency and it is in fact a contraindication for the diet that is ferreted out in childhood and identified. I am talking about a secondary carnitine deficiency. Untreated secondary carnitine deficiency can happen after being on a ketogenic diet or some other non‑genetic cause such as dialysis, malnutrition, or certain drugs (e.g., valproate or pivalate‑containing antibiotics)

And if you become low in carnitine, and brush it off by telling yourself that ketones have lowered because you are just using more of them, there can be health effects to pay that have nothing to do with your ketone availability or ketone levels or even whether you are doing a ketogenic diet at all. Because carnitine is used in a lot of really important processes in the body.

Untreated Secondary Carnitine Deficiency

So what can happen? A lot of things.

If you become ill, and are driven into a forced fasting state, but you don’t have enough carnitine on board to fuel your brain, that can be a big problem that may set you up for increased symptoms or possibly even relapse during your illness.

Some of you who felt amazing and full of energy in the beginning of your ketogenic diet may suddenly notice with your decrease in ketone production came more fatigue, weakness, and exercise intolerance. You may even be developing some chronic myopathy due to insufficient carnitine levels.

Carnitine deficiency may cause muscle necrosis, myoglobinuria, lipid-storage myopathy, hypoglycemia, fatty liver, and hyperammonemia with muscle aches, fatigue, confusion, and cardiomyopathy.

Bhupathiraju, S. N., & Hu, F. B. (2023, October). Carnitine deficiency. Merck Manual Professional Edition.

In fact, you can get a whole bunch of rather mysterious symptoms from just having a secondary carnitine deficiency. Symptoms that are being watched for and even expected in those with a primary carnitine deficiency, but are flying under the radar in our ketogenic diet crowds trying to utilize it as a treatment for mental illness. While significant liver or cardiac disease is less typical with secondary carnitine deficiency, I think ignoring that deficiency sets our body up unnecessarily for problems later down the road that may lead to manifestations of chronic disease. Or for my vulnerable populations using ketogenic diets as a treatment for mental illness, this may lead to more symptoms, limited treatment effects or even relapse.

You Can’t Out‑Keto a Carnitine Deficiency

Again, there are going to be those who suggest this blog post is somehow encouraging the stressful hobby of “ketone chasing” in lieu of just having good metabolic health and insulin sensitivity. And for those individuals I want to point out that pretending secondary carnitine deficiencies don’t exist can have negative effects on your own health goals, irrespective of whether you are using a ketogenic diet for mental illness or a neurological issue. Let’s go over why carnitine levels in this context still matter.

Carnitine supports fatty‑acid oxidation in insulin‑sensitive tissues such as skeletal muscle and the heart. When carnitine is insufficient, fatty‑acid oxidation is impaired, lipid intermediates build up, and this contributes to insulin resistance.

In view of the … beneficial effect of carnitine supplementation on glucose tolerance during insulin-resistant states, carnitine supplementation might be an effective tool for improvement of glucose utilization…

Ringseis, R., Keller, J., & Eder, K. (2012). Role of carnitine in the regulation of glucose homeostasis and insulin sensitivity: evidence from in vivo and in vitro studies with carnitine supplementation and carnitine deficiency. European journal of nutrition, 51(1), 1-18.

Also, you need to know that a carnitine deficiency could be why your triglyceride markers are not where you think the should be after being on your low carb or ketogenic diet so long.

Fasting triglyceride levels … were significantly increased in the low carnitine group compared to normal carnitine group.

Chu, D. Y., Ravelli, M. N., Faltersack, K. M., Woods, A. L., Almane, D., Li, Z., … & Felton, E. A. (2024). Hypocarnitinemia and its effect on seizure control in adult patients with intractable epilepsy on the modified Atkins diet. Frontiers in Nutrition, 10, 1304209.

When carnitine is low hepatic fatty acid oxidation is impaired, and more of the incoming fatty acids are re esterified to triglycerides rather than being oxidized. The liver then packages these triglycerides into VLDL particles and secretes them into the bloodstream, so you see higher fasting plasma triglycerides, mainly VLDL triglycerides, in people with low carnitine levels.

So if you have any interest in metabolic health at all, for any reason, and you are doing a ketogenic diet for that purpose, you need to at least be curious about your carnitine levels. Sure, maybe your ketones are lower because you just do low carb and don’t really moderate your protein. It could be they are low because all those low carb sweeteners are causing a cephalic insulin response. Or it could be you are walking around, and have been for months or even years, with a secondary carnitine deficiency that is working against your long-term health goals.

Bipolar Disorder and Carnitine

Also, you really need to know that a small number of people seem to be unusually sensitive to carnitine in the bipolar population. There are published case reports of individuals with bipolar disorder, not on ketogenic diets, who developed mania or psychosis shortly after starting acetyl‑L‑carnitine supplements, with symptoms settling once the supplement was stopped.

Other identified triggers for mania were brain stimulation, energy drinks, acetyl‑L‑carnitine, St. John’s wort, seasonal changes, hormonal changes and viral infections.

Cordeiro, C. R., Côrte-Real, B. R., Saraiva, R., Frey, B. N., Kapczinski, F., & de Azevedo Cardoso, T. (2023). Triggers for acute mood episodes in bipolar disorder: A systematic review. Journal of Psychiatric Research, 161, 237-260.

If you have bipolar disorder and you think you may need carnitine supplementation, this is something you need to keep in mind and ideally work with a knowledgeable practitioner around out of an abundance of caution.

Your Doctor Probably Isn’t Checking Your Carnitine Levels

And this gets me on another really important subject. Some of you have doctors who have agreed to monitor your medical ketogenic diet, that have no idea they should be ordering your carnitine panel to watch for this. As is often the case in the metabolic psychiatry world, at least at this stage, you will need to self-advocate. If they order the test, understanding you are on a medical diet in which competent monitoring requires it, they won’t necessarily know how to read it, or how to supplement you appropriately. And that is where it becomes very helpful to work with a dietician from the epilepsy world or a ketogenic professional who is trained and experienced in using ketogenic metabolic therapy for neurological and mental health populations.

Some of you are on medications, like Valproic Acid, and it always blows my mind that your prescribers are sometimes not even checking carnitine levels.

Valproic acid therapy may deplete carnitine stores by various mechanisms such as increased urinary excretion as valproylcarnitine, decreased renal tubular reabsorption, and decreased endogenous production.

Dahash, B. A., & Sankararaman, S. (2023). Carnitine deficiency. In StatPearls [Internet]. StatPearls Publishing.

So if you are on Valproic Acid as a mood stabilizer, even if you are not on a ketogenic diet, your prescriber is (as far as I can tell) supposed to routinely check your carnitine level. And some of you on this medication have gone to your prescriber, telling them you would like to do a ketogenic diet (which could further deplete already low carnitine stores). Often the response is they are just willy-nilly giving you the thumbs up, without even testing or understanding how carnitine is used and needed for successful ketone production.

And to add insult to injury, valproate-induced carnitine depletion contributes to hyperammonemia (think ammonia) and encephalopathy (confusion, decreased consciousness), sometimes even when liver tests are normal. This is a recognized, potentially dangerous complication of ongoing therapy or dosages that are simply too high (overdose).

Conclusion

So someone telling you that your ketones have dropped because “you’re just more fat adapted” may not be a helpful or adequate explanation when we know that a carnitine deficiency can quietly shut down fatty acid oxidation, blunt ketone production, raise triglycerides, worsen symptoms, and undermine the very therapy you are working so hard to do correctly. If you are using ketogenic therapy for neurological or psychiatric conditions, or even just for metabolic health, you owe it to yourself to check your carnitine status instead of assuming everything is fine because someone online told you not to worry.

Low carnitine levels can happen on a ketogenic diet. I just don’t want you to think your ketogenic diet is not working or stopped working for you, when really you just ran out of the very thing you needed more of to make ketones. And if you are one of those people that do need to “chase ketones”, monitoring your carnitine can make all the difference.

As can working with someone like me, in my online program, that walks you through every step and provides wonderful support and community for your healing journey.

Brain Fog Recovery Program

Because you have the right to know all of the ways that you can feel better.

References

Bhupathiraju, S. N., & Hu, F. B. (2023, October). Carnitine deficiency. Merck Manual Professional Edition. https://www.merckmanuals.com/professional/nutritional-disorders/undernutrition/carnitine-deficiency

Chu, D. Y., Ravelli, M. N., Faltersack, K. M., Woods, A. L., Almane, D., Li, Z., … & Felton, E. A. (2024). Hypocarnitinemia and its effect on seizure control in adult patients with intractable epilepsy on the modified Atkins diet. Frontiers in Nutrition, 10, 1304209. https://doi.org/10.3389/fnut.2023.1304209

Dahash, B. A., & Sankararaman, S. (2023). Carnitine deficiency. In StatPearls [Internet]. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK559041/

Evcimen, H., Mania, I., Mathews, M., & Basil, B. (2007). Psychosis precipitated by acetyl‑L‑carnitine in a patient with bipolar disorder. Primary Care Companion to the Journal of Clinical Psychiatry, 9(1), 71–72. https://doi.org/10.4088/PCC.v09n0114d

Goodison, G., Overeem, K., de Monte, V., & Siskind, D. (2017). Mania associated with self‑prescribed acetyl‑L‑carnitine in a man with bipolar I disorder. Australasian Psychiatry, 25(1), 13–14. https://doi.org/10.1177/1039856216658831

Longo N. Carnitine transport and fatty acid oxidation. Biochim Biophys Acta. 2016;1863(10):2422‑2435. https://doi.org/10.1016/j.bbamcr.2016.01.023

Nelson, D. L., Cox, M. M., & Hoskins, A. A. (2021). Lehninger principles of biochemistry (8th ed.). W. H. Freeman.

Patel, A. R., & Nagalli, S. (2020). Valproate toxicity. https://www.ncbi.nlm.nih.gov/books/NBK560898/

Pereyra, A. S., McLaughlin, K. L., Buddo, K. A., & Ellis, J. M. (2023). Medium-chain fatty acid oxidation is independent of l-carnitine in liver and kidney but not in heart and skeletal muscle. American Journal of Physiology-Gastrointestinal and Liver Physiology, 325(4), G287-G294. https://doi.org/10.1152/ajpgi.00105.2023

Ringseis, R., Keller, J., & Eder, K. (2012). Role of carnitine in the regulation of glucose homeostasis and insulin sensitivity: evidence from in vivo and in vitro studies with carnitine supplementation and carnitine deficiency. European journal of nutrition, 51(1), 1-18. https://doi.org/10.1007/s00394-011-0284-2

Rodrigues Cordeiro, C., et al. (2023). Triggers for acute mood episodes in bipolar disorder: A systematic review. Journal of Psychiatric Research, 161, 237–260. https://doi.org/10.1016/j.jpsychires.2023.03.008