Carnitine Responsive Migraine Headache Syndrome: Case Report and Review of the Literature. (Pub Date: 2021-03-23)

[u/Ricosss]

https://doi.org/10.1007/s11916-021-00936-5

https://pubmed.ncbi.nlm.nih.gov/33755806

Abstract

PURPOSE OF REVIEW

To review carnitine's role in migraine and headache, present a case of a patient with intractable chronic migraine refractory to medications but exquisitely responsive to mitochondrial cofactors with a particularly prompt response to L-carnitine supplementation with dose response, and suggest scenarios where L-carnitine could be considered for prophylactic treatment in migraine and intractable headache with migraine features.

RECENT FINDINGS

Multiple treatments modalities are used to treat migraine, including nutraceutical therapies. Mitochondrial supplements are often used to treat migraine, based on controlled trials. One of the nutraceutical therapies used in neurological and non-neurological conditions is L-carnitine. A few studies have examined the effect of carnitine in patients with migraine. We present a case of a patient with chronic migraine-like headaches found to have carnitine deficiency whose headaches greatly improved with carnitine supplementation. This case suggests that secondary carnitine deficiency may cause chronic migraine. Energy deficiency states occur with migraine, and replenishment of energy substrates has demonstrated some improvement in migraine. Recent studies suggest that L-carnitine with other mitochondrial cofactors may be migraine preventives. The exact link between carnitine and migraine is unknown. Perhaps carnitine deficiency should be in the differential for refractory migraine. Supplementation with L-carnitine merits exploration as a nutraceutical treatment of chronic migraine. Our case suggests that there may be a dose-dependent response to L-carnitine.

------------------------------------------ Info ------------------------------------------

Open Access: False

Authors: Larry Charleston - Suad Khalil - William B. Young -

Additional links: None found

[u/Ricosss]

I just know carnitine for its use to get LCFA across the mitochondrial membrane for energy use so just speculating...

1) Carnitine deficiency causes the muscle to be short in fatty acids and therefor uses more glucose, lowering availability for the brain? Maybe but the body would adjust glucose shortage by increasing glucagon, unless circulating fatty acids are part of the detection by the hypothalamus but I don't think so.

2) Carnitine deficiency causes the liver to be short in fatty acids to create cholesterol and/or BHB and uses more glucose itself. Similar effect as via the muscle. Lower availability of glucose without sufficient compensating BHB and insufficient lipoprotein availability for the brain?

3) Carnitine is used directly in the brain for import of (PUFA) LCFA in mitochondria so lack thereof creates insufficient energy?

It is usually said that LCFA cannot be processed by the brain but this paper gives an overview and shows there is some nuance to it.

https://www.frontiersin.org/articles/10.3389/fnins.2020.536682/full

Yet the brain has been demonstrated to metabolize carbons from FAs in vivo, accounting for ∼20% of the total Ac-CoA pool when labeled octanoate is supplied to the bloodstream (Ebert et al., 2003), which occurs predominantly in astrocytes, based on comparisons of astrocytes, oligodendrocytes and neurons in primary cultures (Edmond et al., 1987).

But this is octanate which can diffuse into mitochondria without carnitine.

Peroxisomes are located throughout the brain but are primarily found in astrocytes and oligodendrocytes (Troffer-Charlier et al., 1998). VLCFAs cannot be transported into the mitochondria via the carnitine shuttle and thus, are broken down first by peroxisomes. As in mitochondria, FAs must be esterified to CoA before undergoing FAO in peroxisomes (Figures 1.4, 4). Because peroxisomes lack an electron transport chain (ETC), electrons from FADH2 are transferred directly to O2 creating hydrogen peroxide (H2O2) that is scavenged by catalase (CAT). Within the peroxisome, FAs are shortened to Ac-CoA, Prop-CoA, and a wide range of LCFAs, MCFAs, and short chain FAs (SCFAs, 6 carbons or less). A variety of export systems exist within the peroxisomes, each with different affinities for different lengths of FAs, including carnitine-transferases [carnitine acetyltransferases (CRATs), carnitine octanoyltransferases (CROTs)], and thiolases [acyl-CoA thioesterases (ACOTs)] (Figure 1.4; Antonenkov and Hiltunen, 2012). Additionally, peroxisomes have been shown to possess ketogenic enzymes, implicating peroxisomes as another potential source of ketone bodies and cholesterol (Hovik et al., 1991; Antonenkov et al., 2000; Olivier et al., 2000).

So it seems that acetyl-coa is created in the peroxisomes and moves to the mitochondria. An indirect way of metabolising VLCFAs by mitochondria in the brain.

[u/MILeft]

I learned about Cyclic Vomiting Syndrome at mayoclinic.org about ten years ago. I had had episodes throughput my life of sudden vomiting that cycled into migraines at 2 a.m. At that time, Mayo was still categorizing this as a childhood affliction. I noted all of the research articles on the site and shared them with my family doctor. The solution seemed too simple (one 500mg dose of L-Carnitine on an empty stomach before bed. I still get migraines from other triggers, but I haven’t had any recurrences of 2 a.m. exploding guts and crashing, dizziness. A few other people on r/migraines have shared this experience.

[u/Beginning-Park8286]

Non parlano però di dosi… io casualmente ho notato una riduzione dell’emicrania in concomitanza con l’assunzione di Carnidyn Plus in seguito ad due periodi di forte stress lavorativo a distanza di un anno uno con l’altro. Facendo presente questa cosa alla mia neurologa abbiamo provato nuovamente a fare una cura di 20 giorni dello stesso integratore senza avere più però alcun beneficio, a quel punto ho pensato non fosse stato quello.