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Long-chain acylcarnitine deficiency in CFS. Potential involvement of altered carnitin

Dolphin

Senior Member
Messages
17,567
Australian study just out
Authors: Stephanie E Reuter & Allan M Evans

Title: Long-chain acylcarnitine deficiency in chronic fatigue syndrome patients. Potential involvement of altered carnitine palmitoyltransferase-I activity

Journal: Journal of Internal Medicine

Date: 2011

Abstract:

Objective:  The underlying aetiology of chronic fatigue syndrome is currently unknown; however, in light of carnitines critical role in mitochondrial energy production, it has been suggested that chronic fatigue syndrome may be associated with altered carnitine homeostasis. This study was conducted to comparatively examine full endogenous carnitine profiles in chronic fatigue syndrome patients and healthy controls.

Design:  A cross-sectional, observational study.

Setting and subjects:  Forty-four patients with chronic fatigue syndrome and 49 age- and gender-matched healthy controls were recruited from the community and studied at the School of Pharmacy & Medical Sciences, University of South Australia.

Main outcome measures:  All participants completed a fatigue severity scale questionnaire and had a single fasting blood sample collected which was analysed for L-carnitine and 35 individual acylcarnitine concentrations in plasma by LC-MS/MS.

Results:  Chronic fatigue syndrome patients exhibited significantly altered concentrations of C8:1, C12DC, C14, C16:1, C18, C18:1, C18:2 and C18:1-OH acylcarnitines; of particular note, oleyl-L-carnitine (C18:1) and linoleyl-L-carnitine (C18:2) were, on average, 30-40% lower in patients than controls (p<0.0001). Significant correlations between acylcarnitine concentrations and clinical symptomology were also demonstrated.

Conclusions: It is proposed that this disturbance in carnitine homeostasis is a result of a reduction in carnitine palmitoyltransferase-I (CPT-I) activity, possibly due to the accumulation of omega-6 fatty acids previously observed in this patient population. It is hypothesised that the administration of omega-3 fatty acids in combination with L-carnitine would increase CPT-I activity and improve chronic fatigue syndrome symptomology.
 

Dolphin

Senior Member
Messages
17,567
Carnitine is the one supplement I know has helped me. I know from stopping initially because of cost (until I found cheaper sources) and then temporarily supply issues.
This was at a dosage of 3g/day (3000mg/day). I reckon a lot of people take less and may not then give it a fair. Sometimes it is sold at 250mg or even 100mg tablets. When I first got it, it was 100mg tablets so I was taking 30 tablets a day. If I hadn't known about the Pliopys study, I wouldn't have taken that dose.

The full text of:
Vermeulen RCW, Scholte HR. Exploratory open label, randomized study of acetyl- and
propionylcarnitine in chronic fatigue syndrome. Psychosom Med 2004; 66(2): 276-282.
is at:
http://www.cfids-cab.org/cfs-inform/CFStreatment/vermeulen.scholte04.pdf

Results: Clinical global impression of change after treatment showed considerable improvement in 59% of the patients in the acetylcarnitine group and 63% in the propionylcarnitine group, but less in the acetylcarnitine plus propionylcarnitine
group (37%). Acetylcarnitine significantly improved mental fatigue (p=.015) and propionylcarnitine improved general fatigue (p=.004). Attention concentration improved in all groups, whereas pain complaints did not decrease in any group. Two weeks after treatment, worsening of fatigue was experienced by 52%, 50%, and 37% in the acetylcarnitine, propionylcarnitine, and combined group, respectively. In the acetylcarnitine group, but not in the other groups, the changes in plasma carnitine levels
correlated with clinical improvement.
I think the fact that people got worse when they stopped taking it is extra evidence that it was helping. I remember reading that the authors thought what had happened was the patients had got used to a higher level of functioning with the carnitine which they couldn't maintain without it.
 

Dolphin

Senior Member
Messages
17,567
The authors try to link the findings with viral e.g. XMRV, research:
Whilst the cause of this proposed impairment of mitochondrial fatty acid oxidation in chronic fatigue syndrome patients is unknown, it is possible that this may be linked to the recent finding that chronic fatigue syndrome is associated with an increase in the incidence of viral infection [2, 3, 9]. Previous research has indicated that viral infection may result in altered fatty acid oxidation [48] and therefore it is
feasible that the condition may be triggered by a viral infection which leads to a disruption in free fatty acid and carnitine homeostasis, thereby impacting on the clinical condition of these patients. This hypothesis warrants further investigation.

==============
I was reading it and wondering how relevant the findings were - the carnitines looked a bit random (not that I'm an expert on the different ones).

So I thought this was very interesting:
The findings of a previous study by Maes et al [36] further support our hypothesis. In their study, endogenous levels of fatty acids were examined in 22 chronic fatigue syndrome patients and 12 healthy controls and it was demonstrated that chronic fatigue syndrome was accompanied by increased levels of omega-6 poly-unsaturated fatty acids and mono-unsaturated fatty acids. Interestingly, of the fatty acids measured by Maes et al [36] for which the corresponding acylcarnitine was quantified in the present study (C14, C16, C16:1, C18, C18:1, C18:2), for 5 of the 6 cases there was a significant reduction in acylcarnitine levels and an increase in corresponding free fatty acid levels (C14, C16:1, C18, C18:1 & C18:2). In fact,
when our findings are linked with those of Maes et al [36], it can be speculated that the ratio of free fatty acid to acylcarnitine for these acyl groups is approximately 2- to 3-fold higher in chronic fatigue syndrome patients than in healthy controls, indicating a substantial disruption in fatty acid/carnitine homeostasis in these patients. This may be due to either: (1) a reduction in the activity of AcylCoA synthase required for the
conversion of free fatty acid to AcylCoA; or (2) reduced activity of CPT-I. As CPT-I is the rate-controlling enzyme in mitochondrial fatty acid oxidation [37], it is hypothesised, based on these findings, that a reduction in CPT-I activity contributes to the symptomology of chronic fatigue syndrome.
 

glenp

"and this too shall pass"
Messages
776
Location
Vancouver Canada suburbs
Thank you so much for posting this.

I am told that it is not allowed here in Canada. I have to buy it under the table- and the date has been erased. If anyone knows how I might get it please let me know. I have tried getting it online but they say its not legal to send it to Canada. I pay $55 for the only one i can find under the table here - Natures Design Acetyl-L-Carnitine 60-v caps 500 mg-- with the date rubbed off

I just sent the link to the abstract to Health Canada - will see what their reply is. I explained that it is a recommended treatment for CFS and we have to buy it illegally

glen
 

Dolphin

Senior Member
Messages
17,567
These days I take acetyl l-carnitine and l-carnitine. I find acetyl l-carnitine is the one that tends to be available as powder - it's cheaper as powder. I get that in the UK. iherb.com and puritan's pride have good prices for l-carnitine. Canada must be very strict - I didn't know any countries were strict about carnitine (one hears it about some other things e.g. hormones, Gingko Biloba, etc).
 

justy

Donate Advocate Demonstrate
Messages
5,524
Location
U.K
Thanks for posting this Dolphin. I found out that my carnitine levels where low when i had Mitochondrial testing done. I have Acetyl - l -carnitine in powder form but havent started taking it yet. Its good to be reminded of it though and will try and speed up ther introduction of my supplements. I always have a problem as i am a bit phobic about taking new things as i have had severe reactions drugs, supplements and homeopathy.

Why would it be so strictly controlled in Canada?
 

Dolphin

Senior Member
Messages
17,567
Hey dolphin why do you take both forms?
This Dutch study:
http://www.cfids-cab.org/cfs-inform/....scholte04.pdf
found that
"Acetylcarnitine significantly improved mental fatigue (p=.015) and propionylcarnitine improved general fatigue (p=.004)."
I think I have read this before from other studies (not CFS).

From what I can make out, taking propionylcarnitine (which I may have only seen offered once and I think was dear) is somewhat like taking l-carnitine. The Pliopys et al study used l-carnitine only.
is a bit like taking l-carnitine.

But then I have the dilemma that the combined group in the Dutch study didn't do so well:
Clinical global impression of change after treatment showed considerable improvement in 59% of the patients in the acetylcarnitine group and 63% in the propionylcarnitine group, but less in the acetylcarnitine plus propionylcarnitine
group (37%).
 

richvank

Senior Member
Messages
2,732
Hi, all.

I would like to note that there have been several studies published about carnitine levels in ME/CFS, and most show low carnitine.
For what it's worth, the explanation for this in the GD-MCB hypothesis is that it is known that some carnitine normally comes in
from meat in the diet, and some is synthesized in the body. The latter requires methylation reactions, starting with the amino
acid lysine. There is a partial block of the methylation cycle in ME/CFS, producing a deficit in methylation capacity. Among
the many effects of this is a deficit in synthesis of carnitine.

Supplementing L-carnitine or acetyl-L-carnitine can provide benefit to some PWCs, but it is temporary, because it does not
address the fundamental problem, which is the partial block in the methylation cycle. Treatment to lift this partial block has
the potential to restore normal synthesis of carnitine as well as restoring many other biochemical pathways to normal. More information on this is
available at www.cfsresearch.org by clicking on CFS/M.E. and then on my name.

Best regards,

Rich
 

Dolphin

Senior Member
Messages
17,567
Thanks for pointing out Rich how you feel carnitine fits into the model you propose.

Supplementing L-carnitine or acetyl-L-carnitine can provide benefit to some PWCs, but it is temporary, because it does not
address the fundamental problem, which is the partial block in the methylation cycle.
Temporary is an ambiguous word here. I have generally sustained the higher level of functioning when continuing to take it.
 

August59

Daughters High School Graduation
Messages
1,617
Location
Upstate SC, USA
I think I had this test done when I wen to Mayo Clinic. It had several "high-lows" that I questioned, but they explained that they were looking for very specific "high-low" models that represented a genetic abnormality?

I'll have to dig out and look. Thanks
 

richvank

Senior Member
Messages
2,732
Thanks for pointing out Rich how you feel carnitine fits into the model you propose.

Temporary is an ambiguous word here. I have generally sustained the higher level of functioning when continuing to take it.

Hi, Dolphin.

Yes, "temporary" is ambiguous here. What I meant was that it is not a permanent fix. One has to keep taking it to experience the benefit, as you wrote.

Also, some PWCs don't experience a benefit at all from supplementing carnitine. I think the reason for that is that there are other problems beside low carnitine that are limiting the ability of their mitochondria to produce ATP at normal rates. I think that these other problems stem also from the partial block in the methylation cycle and the depletion of glutathione. They include oxidative stress, buildup of toxins which block enzymes and act as adducts on DNA, increase in calcium and lactic acid, decrease in magnesium, and deficiencies in production of coenzyme Q10 and creatine, both of which also require methylation for their synthesis within the body. All of these have been documented by lab testing, all of them are known to be produced by this fundamental cause, and all are known to hinder mitochondrial function. Dr. Myhill has been able to help mito function in quite a few patients with her mito support package, which includes carnitine, co Q10, magnesium, B vitamins and D-ribose. However, I think that lifting the methylation cycle partial block is a more fundamental approach that has the potential to correct the root cause, and be a permanent fix. A small number of PWCs have found it to be so, but most are not completely recovered after doing this treatment. There appear to be some stubborn impediments to restoring the methylation cycle function and glutathione levels completely. I think that pathogens and perhaps toxins are the main suspects.

Best regards,

Rich
 

Chris

Senior Member
Messages
845
Location
Victoria, BC
Hi, Canadians; Acetyl l-Carnitine is available in Canada, but only as a prescription drug--at very high price--I paid over $100 for I think 100 capsules of 500 mg. each. Your doctor may or may not be familiar with the stuff... Mine was not. The deal was reached apparently between a previous minister of health and a drug company. This is the world we live in, and it will get worse, not better, with the pressure from Codex Alimentarium.. Chris
 

Snow Leopard

Hibernating
Messages
5,902
Location
South Australia
Wow. Acetyl l-Carnitine is being sold in powder forum in Australia on ebay for around 5-10c per gram shipped. I haven't tried it in high (3g/day) doses.
 

Dolphin

Senior Member
Messages
17,567
For anyone in Europe, myprotein.co.uk has it for UK50.99 for 1kg (=1000g) or 5.099p per g (it is slightly dearer for 250g and 500g sizes) plus postage (free in UK for orders over 40 it seems). They have recently set themselves up that they are designed for Europe (price will be in Euro etc - it may end up being slightly dearer but one should see before buying).

Note: I have no financial interest in the company. The general trick is to look out for powder form and it's much cheaper.
 

Cort

Phoenix Rising Founder
More carnitine - this time from the Far East - this was a writeup from the 2007 Conference

http://phoenix-cfs.org/old_site/IACFS07II%20BrainGenes.htm

Hirohiko Kuratsune - Brain Session Summary

BRAIN DYSFUNCTION IS A KEY ABNORMALITY FOR UNDERSTANDING THE STATE OF CHRONIC FATIGUE SYNDROME

First Dr. Kuratsune pointed out several abnormal central nervous system findings that he thinks play a central role in CFS. Chief among these are reduced blood flows and reduced acetyl-carnitine uptake in areas of the brain (prefrontal cortices, anterior cingulate, cerebellum) involved in autonomic nervous system functioning, sleep and concentration, pain and motivation. Since acetyl-carnitine plays an important role in the synthesis of several neurotransmitters, reduced acetyl-carnitine uptake could be associated with reduced activity seen in thosel parts of the brain where it is found. He noted that low serotonergic activity in a specific area of the anterior cingulate produces pain. He believes this suggests that a similar problem in another part of the anterior cingulate could produce the fatigue in CFS. After this summary he presented his hypothesis regarding CFS.

A Hypothesis: The Neuro-molecular Mechanisms Leading to Chronic Fatigue

Dr. Kuratsune believes CFS starts with physical/chemical/biological stressors that perhaps in combination with inherited vulnerabilities cause an injury to the central nervous system (CNS). This CNS dysfunction causes the immune system to pump out cytokines (IFN/TGF-B) that disrupt serotonin activity in the brain and alter HPA axis functioning. Altered HPA axis functioning causes reduced acetyl-carnitine uptake in the brain and this further impairs neurotransmission, particularly in the anterior cingulate, basal ganglia and brainstem. This leads to profound fatigue, memory problems, autonomic nervous system problems (orthostatic intolerance, gastrointestinal discomfort) and the consequent circulation, breathing, muscle and temperature regulation problems in CFS. Immune dysfunction results in pathogen reactivation which further exacerbates the immune problems and via cytokine production further disrupts the central nervous system.
 

Cort

Phoenix Rising Founder
Carnitine is the one supplement I know has helped me. I know from stopping initially because of cost (until I found cheaper sources) and then temporarily supply issues.
This was at a dosage of 3g/day (3000mg/day). I reckon a lot of people take less and may not then give it a fair. Sometimes it is sold at 250mg or even 100mg tablets. When I first got it, it was 100mg tablets so I was taking 30 tablets a day. If I hadn't known about the Pliopys study, I wouldn't have taken that dose.

The full text of:
is at:
http://www.cfids-cab.org/cfs-inform/CFStreatment/vermeulen.scholte04.pdf


I think the fact that people got worse when they stopped taking it is extra evidence that it was helping. I remember reading that the authors thought what had happened was the patients had got used to a higher level of functioning with the carnitine which they couldn't maintain without it.

How funny that was in the Journal of Psychosomatic MEdicine
 

Dolphin

Senior Member
Messages
17,567
Plioplys & Plioplys

Neuropsychobiology. 1997;35(1):16-23.

Amantadine and L-carnitine treatment of Chronic Fatigue Syndrome.
Plioplys AV, Plioplys S.

Chronic Fatigue Syndrome Center, Department of Research, Mercy Hospital Chicago, Ill 60616, USA.

Abstract

Carnitine is essential for mitochondrial energy production. Disturbance in mitochondrial function may contribute to or cause the fatigue seen in Chronic Fatigue Syndrome (CFS) patients. Previous investigations have reported decreased carnitine levels in CFS. Orally administered L-carnitine is an effective medicine in treating the fatigue seen in a number of chronic neurologic diseases. Amantadine is one of the most effective medicines for treating the fatigue seen in multiple sclerosis patients. Isolated reports suggest that it may also be effective in treating CFS patients. Formal investigations of the use of L-carnitine and amantadine for treating CFS have not been previously reported. We treated 30 CFS patients in a crossover design comparing L-carnitine and amantadine. Each medicine was given for 2 months, with a 2-week washout period between medicines. L-Carnitine or amantadine was alternately assigned as fist medicine. Amantadine was poorly tolerated by the CFS patients. Only 15 were able to complete 8 weeks of treatment, the others had to stop taking the medicine due to side effects. In those individuals who completed 8 weeks of treatment, there was no statistically significant difference in any of the clinical parameters that were followed. However, with L-carnitine we found statistically significant clinical improvement in 12 of the 18 studied parameters after 8 weeks of treatment. None of the clinical parameters showed any deterioration. The greatest improvement took place between 4 and 8 weeks of L-carnitine treatment. Only 1 patient was unable to complete 8 weeks of treatment due to diarrhea. L-Carnitine is a safe and very well tolerated medicine which improves the clinical status of CFS patients. In this study we also analyzed clinical and laboratory correlates of CFS symptomatology and improvement parameters.

I'm just making excuses now but perhaps with more than 8 weeks treatment there could have been improvement in some of the other areas. Anyway 12 out of 18 areas isn't bad!