Carnitine Deficiency and OAT Metabolites

[jpredsoxdude00]

I have recently posted in the genetics forums regarding carnitine transporter SNPs and I am doing more research into carnitine.

A NutrEval I had done a couple of years ago revealed <dl Lactic Acid and ketones in the urine. From what I understand, ketones require carnitine for formation, however this site seems to claim that they use elevated ketones to diagnose carnitine deficiency: http://www.beyondmthfr.com/organic-acid-test-an-essential-tool-for-gut-methylation-problems/

I have also read that carnitine supplementation reduced plasma lactic acid levels, however it seems possible that the body may be using lactic acid for energy if the fatty acid metabolism is impaired, making lactate levels low. My pyruvic acid levels were high-normal.

Does anybody have any insight regarding this?

 

[Isaiah 58:11]

The science behind this is way over my head, but maybe my test results will help you puzzle it out?

I have urine ketones (anywhere from 15 to 160 mg/dl) with some frequency and a carnitine deficiency that shows up when the acyl/free ratio is tested.

My doctor says the urine ketones are caused by mitochondrial dysfunction. Of course, carnitine deficiency causes mitochondrial dysfunction...

When I take acetyl-l carnitine I no longer look deficient on labs, but I still end up with ketones in my urine. I saw a post somewhere here on PR just this morning saying that ALCAR is the wrong form to use if you want to affect Acetyl-CoA and that fumarate is of greater benefit. So it is possible that if I took the correct form of carnitine it would solve the problem.

I see on my only organic acids test that my pyruvic acid was low at 0. I am not sure if I was taking ALCAR then, but I think so.

I hope this sheds light in some way. I have been trying to type and post this for hours... I don't know what causes this but my ketones were about 80 at noon; they seem to very clearly go higher as I feel worse. It is common for this stage to be followed by muscle breakdown and a result of the darkest color on the strip if I think to test.

 

[jpredsoxdude00]

@Isaiah 58:11 this is interesting. Some science says ketones formation requires adequate carnitine levels, but other things I have read also state that excess ketones can be a sign of lower carnitine levels. My L-Carnitine Fumarate arrives tomorrow, so I will see if I notice anything when taking it. I have a hunch that carnitine deficiency may be another of the so-called "great pretenders".

I have not had carnitine levels tested before and the ketones were found on NutrEval and randomly when my symptoms were acting up and a doctor ordered a urine test (they were looking for blood sugar issues, which turned up with reactive hypoglycemia when a 3-hour Glucose Tolerance Test with Insulin was performed.). Carnitine deficiency can be linked to hypoglycemia, but as far as it being related to reactive hypoglycemia specifically, only one study links the two: https://www.ncbi.nlm.nih.gov/pubmed/6406707.

Do you have blood sugar issues and/or reactive hypoglycemia?

 

[Isaiah 58:11]

I do have blood sugar problems. Growing up I had hypoglycemia and had to go to the school nurse for a snack mid-morning. I hated juice and candy and such as it would make me ill. That has shown up at times on labs as an adult, sometimes low, sometimes normal but my normal baseline has crept up and my doctor interprets that as insulin resistance with some of my other labs.

I do not know if I have ever had reactive hypoglycemia.Years ago I described to a doctor what happened/happens after I eat and he said, "Well if that happened before you ate we would bring you in and test you before and after a great big plate of spaghetti." So I always assumed he though it sounded like hypoglycemia, though he probably didn't have much idea that it could occur after eating. Now I mostly just have major brain fog without the sleepiness and nausea after eating, but glucometer looks fine.

On the other hand, there is evidence I have been swinging high as well. I don't really understand it. On a day when I am hungry and feel like eating carbs I can eat a pile of biscuits and gravy (this is an unusual meal) and have a postprandial reading of 85. Other days I have felt fat, sluggish, and gross and end up with postprandial glucose off something like a single piece of Ezekiel bread that will be something like 114. At one point my HBA1c actually came back high.

Interestingly, carnitine improves insulin sensitivity in Type-2 diabetics so this is probably all related.

I was told to take lysine for EBV and have gone on and off of it a few times over the years; I can't see that it makes a difference with these issues even when taking supportive methylation vitamins. I have been shown to be deficient in methionine as well which makes sense (carnitine-wise, overlooking the fact that I crave and eat meat and shouldn't be low in these things at all), but when I have labs done in conjunction with supplementation my carnitine doesn't change. Instead, glutathione rockets into a 'high' lab reading.

I wonder if we are so toxic that methionine is all turned to cysteine instead of carnitine to mop up a mess? That is my leading theory. Or, could it be that a functioning carnitine cycle is perceived as so dangerous that it is shunted into glutathione as a sort of storage? Maybe it is only my own body that works this way... It is probably something else entirely; I have no idea how these systems really work, I only have the internet's For Dummies version in my very damaged brain.

How high do your urine ketones get @jpredsoxdude00 ? Does your diet matter at all? I seem to get them going high after about 12 hours without a good source of carbs. I can't really figure out how dieters take days of extremely low carbs to get trace mounts of ketones and I will have them shoot through the roof if I accidentally have a low-carb breakfast after macaroni, cake, and ice cream the night before. Aren't most people's livers still providing sugar at that point? And why can't I seem to use the ketones at all? When I have used a body composition calculator I see that I often lose about up to 2 pounds per day - mostly of lean mass.

 

[alicec]

From what I understand, ketones require carnitine for formation, however this site seems to claim that they use elevated ketones to diagnose carnitine deficiency:

Carnitine is required to transport fatty acids into the mitochondrion where they are broken down by beta oxidation to acetylCoA and fed into the Kreb's cycle to harvest their energy.

AcetylCoA must condense with oxaloacetate for the Kreb's cycle to proceed and in conditions where oxaloacetate is low, such as fasting or low insulin in diabetes, and the liver has depleted its glycogen stores, the liver converts acetylCoA to ketones. These are sent to the periphery where they can be converted to acetylCoA and used for energy in place of glucose.

Here and here are articles which give detail.

That website makes a lot of dubious claims. If we look for example at primary carnitine deficiency, ketones are low or absent.

There seem to be contradictory claims about the effect of carnitine on lactate but at least in some circumstances carnitine lowers lactate. There seems no doubt that carnitine deficiency can cause lactic acidosis and that the treatment for this is carnitine infusion.

 

[alicec]

Chris Masterjohn has just put together a series on ketones that you may find interesting.

Here are the links to the web page versions:

• This is How Ketogenesis Works | MWM 2.32
• This is How We Burn Ketones for Energy | MWM 2.33
• This is Why We Make Ketones | MWM 2.34
• Ketone Homeostasis During Fasting | MWM 2.35
• Ketoacidosis: The Dark Side of Ketones | MWM 2.36
• Inuit Genetics Show Us Why Evolution Does Not Want Us In Constant Ketosis | MWM 2.37