Carnitine = more fatigue

[Leopardtail]

Did I mention fatigue?

My muscles have developed and so become structurally stronger, presumably on the muscle-fibre level. However, I still have the classic problem of being unable to sustain activity for long without getting physically exhausted (i.e. muscle pain and inability to continue) and later suffering PEM. This is probably due to the underlying mitochondrial abnormalities.

Better lateral thinking - yes, I think I can relate to that. Maybe not entirely down to carnitine but a general result of fixing the gut? I can hold more thoughts in my mind at a time now and work with them, perhaps. Not sure about that though. Still get brain fog after a while. Could be mitos again.

BTW low-carb diets are now being shown to be better at modifying cholesterol than low-fat ones, such as in this meta-analysis.

Off-topic - sorry.

Hi MeSci,

all interesting stuff (re off topic).

Sorry no you were quite specific about energy! I was very fogged earlier, having a bad day.

I suspect that we suffer multiple issues affecting brain function - and that what ails each of us most will do most good when fixed. Carnitine has a wide range of effects, thanks for the research link from De Meier. I can't comment with your level of authority on the gut related items since I had inflammation with very little in the way of dysbiosis - I suspect because my stomach acid remained normal.

The Acetyl form of carnitine acts as an analogue of AcetylCholine (research papers on PubMed for that). That neurotransmitter is considered by some (no idea of the strength of science) to improve alert lateral thinking and creative approaches. I do know that when my diabetes has caused hypoglycaemia of the correct severity to elevate AC that my thoughts did become very lateral and creative if I retained reasonable mental function.

My major cause of brain fog was blood volume. At one point ME/CFS crashed my Insulin response, and I also retained no water I drank irrespective of blood sugars. That meant I had to have two litres saline to fix the issue. My brain function and stamina immediately returned to normal, as did my ability to filter noise. I got full fours hours of 'brain strain' research done in a continuous burst. The improvement was stunning and continued until I passed water.

B.

 

[S.A.]

Hi S.A.,

LCF allows a lot of processes to continue. It was fundamental for me to be able to put on 50 pounds of muscle. I had to eat a bit more. With my weight stabilized, at most are adjustments as things reorganize, I'm back down to the same 1500 calories I've always been on but not putting on water and if I'm careful, not putting on fat. I can say that there is all that much difference. Maybe I burn 100 calories a day more. That is all too easy to eat that much more and then some. Its a vey subtle difference. It does transport fats to the mitochondria and that is the normal way things work. It isn't that suddenly it goes into high gear just burning fat for no reason. It just feels like more energy at the beginning while the body is adjusting. I found a whole capsule too much to start with. If a person starts with perhaps 1/8 to 1/4 of a capsule and if that is comfortable increase. Of those who have this CFS/FMS about 90% have to have the fumarate to be effective and the other 10% have to have the ALCAR to be effective. Some people are not short on it and have no effect at all. Some need more biotin to get it going and for some it is D-ribose that is needed. I know that is a lot of variations, but that is one branch of these things. Since it can start additional layers of healing be careful and note any changes for folate and/or potassium. Rebalancing is often needed after this is started.

That's a good point to watch out for the rebalancing. We got back the 3rd nutraEval since starting treatment and his folate and potassium were both still low even tho he's on so much folate, b12, and b6. Oh and potassium but apparently not enough. That could be a reason for the highs and lows. I also don't have him on biotin. I had taken him off the b complex after the hives (not flush) reaction to increasing niacin and hadn't started trying to titrate the other b vitamins individually.

 

[aaron_c]

Hi Yall,

I know this is an old thread, but I have recently run into the same problem of L-Carnitine and Carnitine-Fumarate causing a somewhat dramatic increase in fatigue.

I have another theory as to why carnitine might make one tired: Inhibition of Glutamate-induced NMDA excitation.

Carnitine prevents glutamate toxicity through increasing binding affinity of glutamate for metabotropic glutamate receptors (as opposed to ionotropic glutamate receptors like NMDA receptors that, in my limited understanding, are how glutamate causes problems). In any case, one way or another the activation of these metabotropic receptors prevents glutamate-induced excitotoxicity [1].

Theoretically, this could also explain why Star-Anise experienced an increase in appetite: Glutamate stimulation of mGluR5 receptor (a metabotropic receptor ie the kind that carnitine helps glutamate attach to) increases appetite in rats.

Assuming this theory holds up and the carnitine is just restoring the brain towards balance, then over time we should get used to the lower NMDA stimulation, and carnitine should stop making us tired. I tested this on myself two or so months ago, and indeed, this is what happened over the course of...I think some number of days. Maybe a week? (Sorry, I didn’t keep notes.) I still take it both to give me energy (too much carnitine now gives me insomnia...as it should, I suppose) and to help me sleep (which it does, when taken in the right amount).

If it helps at all, my thoughts on fatigue that gradually disappears came from experience I (and others) have had with molybdenum. Molybdenum makes a number of people tired when they first take it, with the symptom gradually disappearing over the course of maybe two weeks(?) or so. This occurs--or so the theory goes--because a deficiency of molybdenum prevents sulfite oxidase (SUOX) from converting sulfites into sulfates. The sulfites, in turn, react with cystine to form S-sulfocysteine (SSC), a glutamate analog [3]. But in spite of the fact that the molybdenum is returning the SSC levels back to where they should be, it initially makes people tired to have less glutamatergic signalling. If the theory is right. (I am sorry that I don't know where I read this theory. Unfortunately, the phoenixrising thread that I first read about molybdenum fatigue on got lost when they re-did the web site a few years ago.)

[1] Metab Brain Dis. 2002 Dec;17(4):389-97. Prevention of ammonia and glutamate neurotoxicity by carnitine: molecular mechanisms. Llansola M1, Erceg S, Hernández-Viadel M, Felipo V. <http://www.ncbi.nlm.nih.gov/pubmed/12602515>

[2] Front Endocrinol (Lausanne). 2013; 4: 103. Published online 2013 Aug 15. doi: 10.3389/fendo.2013.00103 PMCID: PMC3744050. Glutamate and GABA in Appetite Regulation. Teresa C. Delgado <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3744050/>

[3] Adv Exp Med Biol. 2013;776:13-9. doi: 10.1007/978-1-4614-6093-0_2. Molybdenum cofactor deficiency: metabolic link between taurine and S-sulfocysteine. Belaidi AA1, Schwarz G. <http://www.ncbi.nlm.nih.gov/pubmed/23392866>

 

[Johnmac]

I got both fatigue & anxiety from LCF, & on Fred's advice switched to liquid carnitine, which I could titrate slowly up from low doses. Now on a whopping 2 mg. But no sfx like with the LCF. Some of us are like this.

 

[aaron_c]

sfx?

 

[Johnmac]

Sfx = side-effects.

 

[nuclearbeaver]

Johnmac, I've been doing Fredd's Methylation Protocol and have had the same experience - increased fatigue and 'anxiety' on L-Carnintine Fumarate. You're the first person I've read as saying you have that experience with this supplement. I'm finding the fatigue unmanageable and the 'anxiety' really difficult. I saw on another thread the advice to lower rather than eliminate the supplement. I'm at 250mg a day at the moment so I intend to drop down tomorrow to 125mg and hopefully I'll get some relief.

I tried adding in TMG which helped a bit but the 'anxiety' and fatigue are still unmanageable, so I will definitely drop the dose down.

A question for you - what does the 'anxiety' feel like? I am only using the term because everyone else labels it anxiety. For me, I have a feeling of being agitated, strongly driven, adrenalised and angry - angry like I want to argue and get in a fight with someone. I would never use the term 'anxiety' to explain this feeling so I don't know if I'm feeling what other people do. It's also like someone is holding the contents of my lower abdomen and shaking it. Is this anything like the 'anxiety' you get on this supplement?

 

[Crux]

L-carnitine is another nitric oxide donor (NO). Great for athletes.

If someone is having negative side effects from it, they might already be producing NO to fight infections, etc.

If that is the case, adding more NO donors can cause inflammation, neurological symptoms, etc.

 

[Johnmac]

My symptoms were agitation/anxiety & exhaustion simultaneously. The agitation was a kind of "don't want to be here, don't want to even be in my body" kind of thing (not suicidal tho). I couldn't think of anything I could do or anything I could be with that would make me feel better.

I rectified this on Freddd's advice by switching to liquid carnitine, which I could titrate up from very low doses. Here's my understanding of how to titrate:

Put 98 drops of water in a small glass. Put 1 drop of liquid carnitine in.

Take 1 drop of that solution & put it in a glass of water. That gives you a 100mcg dose.

Drink that on an empty stomach. Do that 3 times a day.

Next day do the same, but add one extra drop to one dose. Day 3 add one extra drop to 2 doses - etc. So you double the overall dose every 3 days.

If you want to speed up the titration, you can take the drops hourly.

Keep the original solution in the frig for the day. Discard at the end of the day.

If you get anxious, drop back to the original dose. Then when it abates, increase by 1 drop a day.

After several months to a year of 'feathering', you end up stable on 1 to 2-3 doses a day.


Too much carinitine = anxiety

Too little carnitine = depression


This is what Fred wrote about this:

The anxiety-depression/despair set of symptoms is a tip-off. That is a frequent variation of how people react. It usually happens when their AdoCbl-Carnitine end of things has been more deficient than the MeCbl-Metafolin side. Things are more hung up on the ATP side than the methylation side... The Jarrow liquid carnitine is free-base and generally works for both ALCAR and LCF needing people. The carnitine takes effect quickly... The anxiety appears on the uphill. increasing serum level, and the depression is on the drop down after peak. You may have a reaction at 200mcg or not until 20mg or who knows... Since you have verified that you get the depression and the anxiety at opposite ends of the carnitine period in the body and that is a pattern I recognize with the solution being to find the balance point and titrate slowly up from there... The despair/depression appear to be the CNS carnitine crash with the anxiety at the start of the increase in carnitine. In others I have talked with there was a balance point. The DQ has to be taken regularly and managed for steadiness and balance. The anxiety is high carnitine (relatively) and the depression is the low carnitine.

...I know that is a tiny dose. Some people are terribly sensitive. You can usually increase 50% to 100% daily until you get that first "hit". Then typically the daily dose can increase 25% as long as it is comfortable to do so. I know it seems tiny but somewhere between 100mcg and 1mg most hypersensitives hit the effect. If not, one just keeps going. A 25% per day increase is often unperceivable, which is just fine. Eventually it gets where it needs to be.

[And when I hit some anxiety]: Cut back the dose by about 25% and continue. That way you probably won't go to the depression, then let it level out and then titrate by a small amount again after a couple of days.

Also the drop can be put into a spoon of water, just enough to make sure you get the bulk of it into your stomach.

You do drink all of whatever you dilute into. The purpose is not dilution which is why you threw me. The If you put a drop or 2 drops or 32 drops into a spoon and then into your mouth, how much will reach the stomach? I don't know. If you put it in an ounce or more of water and drink it, the drop that remains won't make any difference.

Johnmac, I've been doing Fredd's Methylation Protocol and have had the same experience - increased fatigue and 'anxiety' on L-Carnintine Fumarate. You're the first person I've read as saying you have that experience with this supplement. I'm finding the fatigue unmanageable and the 'anxiety' really difficult. I saw on another thread the advice to lower rather than eliminate the supplement. I'm at 250mg a day at the moment so I intend to drop down tomorrow to 125mg and hopefully I'll get some relief.

I tried adding in TMG which helped a bit but the 'anxiety' and fatigue are still unmanageable, so I will definitely drop the dose down.

A question for you - what does the 'anxiety' feel like? I am only using the term because everyone else labels it anxiety. For me, I have a feeling of being agitated, strongly driven, adrenalised and angry - angry like I want to argue and get in a fight with someone. I would never use the term 'anxiety' to explain this feeling so I don't know if I'm feeling what other people do. It's also like someone is holding the contents of my lower abdomen and shaking it. Is this anything like the 'anxiety' you get on this supplement?

Quite a few others have experienced this (carnitine is famous for it). 125mg would have been way too much for most of us.

I found that continuing on small doses of carnitine was better than stopping carnitine.

 

[nuclearbeaver]

Thanks for that info, Johnmac! The other thing that I seem to have different is that the agitation/frustration/highly driven doesn't start immediately, it slowly gets stronger over several days. Most people seem to have a reaction the same day they take it.

I haven't had depression as a result of the carnitine but along with the agitated/frustrated/driven feeling I feel almost no emotion at all.

Can anyone else describe what their experience of 'anxiety' was like while on carnintine? I'd be curious to hear.

 

[Johnmac]

Thanks for that info, Johnmac! The other thing that I seem to have different is that the agitation/frustration/highly driven doesn't start immediately, it slowly gets stronger over several days. Most people seem to have a reaction the same day they take it.

I haven't had depression as a result of the carnitine but along with the agitated/frustrated/driven feeling I feel almost no emotion at all.

Can anyone else describe what their experience of 'anxiety' was like while on carnintine? I'd be curious to hear.

Mine generally built over a few days too. Then took a few days (sometimes longer) to dissipate.

 

[Tammy]

Ditto to what everyone said about the harmful affects of carnitine...............BEWARE of carnitine.

 

[Ninan]

@Leopardtail
I just noticed that ALCAR seems to take a toll on my adrenals. Something I definitely don't need. I have candida issues and problems with allergies so I eat very low carb but can D-ribose work as well as sugar for helping the adrenals while taking ALCAR?

 

[Ninan]

Btw: Precisely how does ALCAR stress the adrenals? Through which mechanism, any ideas?

 

[stridor]

@Ninan
I tried ALCAR 4 times and it was a disaster Fog, fatigue and dark mood and thinking. I am on hydrocortisone and really don't have enough adrenal function for this to affect. All I am trying to say is that carnitine can impact more than just adrenals.
It was a mystery to me at the time. Intuitively, I knew that carnitine was going to be integral to my recovery and I could not understand why it would slam me down.
Even after I came here I was was "carnitine shy" for quite a while and held off. But the difference was amazing. Taking l-carnitine fumerate instead was an important step for me.

 

[aaron_c]

Precisely how does ALCAR stress the adrenals?

Hi Ninan.

Glutamate stimulates the synthesis of steroid hormones by the adrenals, and some of the supplements you will find for "adrenal fatigue" work through this mechanism. As I said above, carnitine increases the affinity of glutamate for metabotropic glutamate receptors. One study found that an agonist of GRM2 and GRM3 (metabotropic glutamate receptors) decreased aldosterone and cortisol production in adrenocortical cancer cells in vitro [1]. So I think this could explain why carnitine slows down your adrenals.

As I said above, my experience has been that carnitine stops causing fatigue after roughly a week or two--but I'm only speaking for myself.

[1] Glutamate receptors and the regulation of steroidogenesis in the human adrenal gland: the metabotropic pathway. http://www.ncbi.nlm.nih.gov/pubmed/24080311

 

[Ninan]

Hi Ninan.

Glutamate stimulates the synthesis of steroid hormones by the adrenals, and some of the supplements you will find for "adrenal fatigue" work through this mechanism. As I said above, carnitine increases the affinity of glutamate for metabotropic glutamate receptors. One study that found that an agonist of GRM2 and GRM3 (metabotropic glutamate receptors) decreased aldosterone and cortisol production in adrenocortical cancer cells in vitro [1]. So I think this could explain why carnitine slows down your adrenals.

As I said above, my experience has been that carnitine stops causing fatigue after roughly a week or two--but I'm only speaking for myself.

[1] Glutamate receptors and the regulation of steroidogenesis in the human adrenal gland: the metabotropic pathway. http://www.ncbi.nlm.nih.gov/pubmed/24080311

I see. Thanks for the explanation, @aaron_c Sounds right. Maybe I'll try it again when my adrenals are a bit happier.

 

[Oberon]

I got both fatigue & anxiety from LCF, & on Fred's advice switched to liquid carnitine, which I could titrate slowly up from low doses. Now on a whopping 2 mg. But no sfx like with the LCF. Some of us are like this.

To add myself as a secondary case study to this I also went through the same cycle of first trying LCF (Doctor's Best) and then changing to Liquid Carnitine (Jarrow). After taking LCF my anxiety, agitation, and irritability skyrocketed. To confirm this I tried it a few times uncomfortably.

I then switched to the Liquid Carnitine at the same dosage level rather than titrating and the only side effects experienced were increased hunger and slight irritability. For the first while my energy levels had a major increase, but this levelled off after a month or so.

 

[bigmillz]

@Ninan
I tried ALCAR 4 times and it was a disaster Fog, fatigue and dark mood and thinking. I am on hydrocortisone and really don't have enough adrenal function for this to affect. All I am trying to say is that carnitine can impact more than just adrenals.
It was a mystery to me at the time. Intuitively, I knew that carnitine was going to be integral to my recovery and I could not understand why it would slam me down.
Even after I came here I was was "carnitine shy" for quite a while and held off. But the difference was amazing. Taking l-carnitine fumerate instead was an important step for me.

Ran into your post from a search and I think I'm having the same issue. I started with LCF and it didn't seem to be doing much, so after a week I switched to ALCAR. it felt like rocket fuel at first, but I've noticed increasing fatigue and moodiness, especially after the 2nd 500mg dose everyday.

LCF did the trick for you? What dose did you start at?

 

[stridor]

@bigmillz
Freddd says that we are more-or-less in 2 camps here. Most of us respond better to LCF but a sizable minority do better with ALCAR.
If you had a (+) response to ALCAR then play around with the dose before you move on. I started on 500 mg and had to cut back to 250 mg of LCF. I do not do well when I take 500 mg like some others. I don' t know whether the 2 forms are equivalent in terms of dosing (suspect they may be) but I would be wiped out if I tried taking a gram a day.