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Interview: Parkinson’s Disease, Acetyl-L-Carnitine, Alpha Lipoic Acid, CoQ10 and Melatonin

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Parkinson’s Disease, Acetyl-L-Carnitine, Alpha Lipoic Acid, CoQ10 and Melatonin
Oliver T. Phillipson, Ph.D.
School of Medical Sciences, University of Bristol
University Walk, Bristol BS8 1TD, UK
+44 117 9239228 / +44 117 9304263 (FAX)

“Management of the Aging Risk Factor for Parkinson's Disease,”
Neurobiol Aging, 2013 Oct 10. [Epub ahead of print] 50271

Kirk Hamilton: Can you share with us your educational background and current position?

Oliver T. Phillipson: I am a medical scientist with degrees in Medicine, Surgery and Physiology from Oxford
University, United Kingdom. After internships I took a PhD in neuroscience at University of London, followed
by postdoctoral position at the MRC Neurochemical Pharmacology Unit, Cambridge, UK, and then a travelling
Fellowship at the Karolinska Institute, Sweden. Then I took up a lectureship post at the University of Bristol
Medical School, where I remained undertaking further research into pathways controlling dopamine neurons in
the central nervous system with special reference to the clinical problems presented by schizophrenia and
Parkinson's disease. I am now 71, and retain a Visiting Fellowship at the University continuing a study of the
effects of aging on Parkinson's disease (PD). I have now accumulated 40 years experience in the neuroscience
underlying these clinical problems.

KH: What got you interested in studying the role of energy metabolism and Parkinson's disease?

OTP: There were many reasons which centre around the association of normal aging, mitochondrial
dysfunction, and abnormal energy metabolism with the condition of PD. Aging is the main risk factor for the
development and progression of the commonest form of the disease. Moreover many of the disease markers for
PD are also found in normal aging though in less severe form. This includes recent findings of under expressed
epigenetic signaling factors which control energy metabolism and antioxidant control. In some respects,
therefore, but not all, PD can be viewed as a severe aging process. Putting right these energy deficits resulting
from gene and mitochondrial dysfunction seen in both normal aging and PD, might therefore be an effective way
to reduce the impact of disease progression. Results from research into normal aging have yielded nutritional
methods by which this might be achieved.

KH: How may alpha lipoic acid, acetyl-L-carnitine, coenzyme Q10 and melatonin alter the pathophysiology
of PD?

OTP: The loss of dopamine neurons, traditionally the focus of concern, and more recently the accumulation of
the pathogenic misfolded protein alpha-synuclein, are the indirect consequence of this deeper energy deficit and
mitochondrial dysfunction producing severe oxidative stress. To summarize, this combination of supplements
(derived from research into normal aging), is known to improve energy metabolism, mitochondrial function and
reduce oxidative stresses which are known to be damaging to key elements of metabolic pathways important for
energy production. Perhaps more importantly they also improve the epigenetic expression of factors which
control the de novo biosynthesis of mitochondria and maintain their structural integrity, including the activity of
numerous essential component enzymes and enzyme complexes involved in the extraction of energy from
carbohydrate and fatty acid sources to produce energy rich phosphates, thus providing a more secure source of
fuel for a host of cellular functions. Lipoic acid, acety-L-carnitine and coenzyme Q10 influence different
components of these complex biochemical networks, working in synergy to support energy metabolism. This has
been shown to protect dopamine neurons and improve defenses against protein misfolding and inflammation,
thus reducing the risk of disease progression.

Reduction in nocturnal melatonin secretion is another important source of mitochondrial dysfunction whichaccompanies aging and replacement enhances antioxidant protection, particularly against reactive nitrogen species. More to the point, for the patient, melatonin replacement provides a better quality of sleep and hence quality of life the next day. This aspect has been specifically documented in the case of PD, which is usually accompanied by chronic insomnia.

KH: Have there been any trials using this combination of supplements?

OTP: Experience is limited to case history evidence thus far, and more such evidence is required before
launching larger trials.


My current advice for those wishing to employ these supplements is as follows:

1) Slow release melatonin, 2mg at night; Circadian (Neurim Pharmaceuticals) (prescription: family practioner).

2) Alpha lipoic acid 200-400mg per day and acetyl-L-carnitine 250-500mg per day, both taken together, starting
with the lower dose, right after a meal, and in divided dose for the higher dose.
 (OTC supplements; available in any reputable health food retailers).

3) Coenzyme Q10 200mg per day, rising slowly (month by month) until control is achieved, not exceeding
800mg maximum per day, in divided doses, then 200-400mg per day as maintenance dose / in divided doses.

4) Vitamin E (400IU once a day with coenzyme Q). (OTC)

5) Acetyl-L-carnitine 250mg at night. (OTC)

Please consult your family practitioner before starting this procedure.

KH: Can you tell us about other studies which have used these agents?

OTP: These nutrients have been used in the following manner in multiple trials:

- Alpha lipoic acid has been in clinical use for over 50 years treating retinopathy and peripheral
neuropathy associated with diabetes; also for hypertension, and for inflammation.

- Acetyl-L-carnitine has been used for over 20 years for treating Alzheimer’s' dementia and a variety of
peripheral neuropathies. Although efficacy for the former is debated, promising results have been found
in the latter, improving conduction velocity and relieving pain.

- Coenzyme Q10 has been trialed in PD, Huntingdon's disease, Alzheimer's, Friedreich's ataxia and
amyotrophic lateral sclerosis. The latest phase III trial has declared it to be ineffective for PD, although
safe when used as monotherapy. However, it appears essential as a component of the combination
suggested here, as melatonin alone or melatonin plus the lipoic acid/acetyl-L-carnitine combination is
not effective without coenzyme Q10. Only with the full combination indicated here does control of PD
progression occur. This is due to the essential role of CoQ in maintaining electron transport in the inner
membrane of mitochondria. However, without the backup of gene regulation, and improved extraction of
energy from nutritional sources provided by the other components, CoQ on its own seems insufficient to
control PD.

- Melatonin has been used safely for decades in the USA and is now generally available as a prescription
for insomnia. In the slow release formula it is said to mimic the natural nocturnal secretion profile.

KH: Were there any side effects?

OTP: I have personally taken these doses of the combined supplements to check on side effects, since I believe
that I should not recommend agents which I would not like to take myself. I can report that, although I have not
tried the very highest dose of CoQ for an extended period, all the others at the doses given are entirely without
adverse side effects in the long term in my case. Reports in the literature suggest that all these agents are well
tolerated, are apparently without ill effects and safe at these doses. Some reports describe gastrointestinal side
effects, although not significantly different from those in control groups, while laboratory tests reveal no signs of
toxicity. Perhaps the best testimony of safety is the decade’s long experience of safe use for all these

KH: Who is a candidate for this combination therapy?


OTP: At this stage the most suitable cases will be those in the early stages of PD (with symptoms for 5 years or less), whether or not they have started on, or responded to conventional therapy.

KH: How can the public or health professionals use this information?

OTP: The public can be confident that employing these methods to manage progression of PD is a low risk
procedure. They need to be aware that the greater risk they face is the risk of continued progression with
conventional treatment alone (100%). That is not a risk, it is a certainty! Although it is unknown at present how
many patients will respond favorably to this management, even if only 50% respond well, this would be an
improvement in the present situation facing patients. Subjects willing to proceed, (subject to approval by their
family practitioner), should be prepared to wait for up to a year before expecting an improved outlook, as the
biochemical changes induced work with a slow time course to repair the multiple cellular dysfunctions
underlying the symptoms of PD. This differs markedly from conventional pharmaceuticals, which usually yield
results in hours and days. The method is aimed at managing the deeper underlying disease process associated
with aging, and not directly the superficial symptoms, which only occur after a long period of latent developing
pathology. Since progression of disease proceeds slowly, use of these agents should be accompanied by some
form of record or diary keeping by patients (monthly at least) so that significant events are regularly monitored.
Health professionals may also wish to use a standard rating scale.



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Interesting. But it seems once a week a different researcher comes up with a different course of action. I'm afraid to start ONE in fear that another researcher comes up with a different, more exciting course to try. This one said you really need to do it for a year before you can expect any measurable response. In a years time, 50 other studies will pop up.

Which one to take????

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What is your opinion do you think it is safe to try?

As Dr. Phillipson says, this should first be discussed with your doctor. However, the supplements he mentions have all been studied extensively and found to be safe for human use, so unless your doctor states otherwise, they should not be harmful. Here is the abstract of Dr. Phillopson's review:



Neurobiol Aging. 2014 Apr;35(4):847-57. doi: 10.1016/j.neurobiolaging.2013.10.073. Epub 2013 Oct 10.
Management of the aging risk factor for Parkinson's disease. Abstract

The aging risk factor for Parkinson's disease is described in terms of specific disease markers including mitochondrial and gene dysfunctions relevant to energy metabolism. This review details evidence for the ability of nutritional agents to manage these aging risk factors. The combination of alpha lipoic acid, acetyl-l-carnitine, coenzyme Q10, and melatonin supports energy metabolism via carbohydrate and fatty acid utilization, assists electron transport and adenosine triphosphate synthesis, counters oxidative and nitrosative stress, and raises defenses against protein misfolding, inflammatory stimuli, iron, and other endogenous or xenobiotic toxins. These effects are supported by gene expression via the antioxidant response element (ARE; Keap/Nrf2 pathway), and by peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1 alpha), a transcription coactivator, which regulates gene expression for energy metabolism and mitochondrial biogenesis, and maintains the structural integrity of mitochondria. The effectiveness and synergies of the combination against disease risks are discussed in relation to gene action, dopamine cell loss, and the accumulation and spread of pathology via misfolded alpha-synuclein. In addition there are potential synergies to support a neurorestorative role via glial derived neurotrophic factor expression.

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Interesting. But it seems once a week a different researcher comes up with a different course of action. I'm afraid to start ONE in fear that another researcher comes up with a different, more exciting course to try. This one said you really need to do it for a year before you can expect any measurable response. In a years time, 50 other studies will pop up.

Which one to take????

You make a very good point indeed. I will say that all of the substances mentioned have been studied extensively in humans, and CoQ10, vitamin E, and melatonin have been studied specifically for PD. Assuming your doctor agrees, a one-year trial should not pose a risk.


You might like to read the entire review to help in decision-making:  http://www.neurobiologyofaging.org/article/S0197-4580%2813%2900525-3/fulltext

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Would this be in addition to sinemet, amantadine ect?

Yes, this would be in addition to PD drugs. None of the supplements mentioned replaces the PD medications.

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How do you determine the brand name supplement to take? Since this regime is supplements I want to make sure I get the right kind. I am going to discuss with MDS but after reading the articles I may try it.

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How do you determine the brand name supplement to take? Since this regime is supplements I want to make sure I get the right kind. I am going to discuss with MDS but after reading the articles I may try it.

I subscribe to ConsumerLabs, an independent agency that tests supplements. Here are some that have passed ConsumerLabs testing and are approved by them:



GNC Acetyl-L-carnitine 500

Jarrow Formulas Acetyl-L-carnitine 500

Twinlab Acetyl-L-carnitine 500 to 2000

Vitamin Shoppe Acetyl-L-carnitine 500


Alpha lipoic acid

Bluebonnet Alpha lipoic acid 600 mg

Natrol Alpha lipoic acid 600 mg

Natures Bounty Super Alpha lipoic acid 200

Solgar Alpha lipoic acid 200 mg


Vitamin E

GNC Natural E 400 IU

Life Extension Pure Natural Vitamin E 400 IU

Nature Made Vitamin E 400 IU

Puritan's Pride Premium Natural E 400 IU mixed tocopherols



CVS Pharmacy CoQ10 100 mg

Finest Nutrition (Walgreens) CoQ10 200 mg

GNC Preventive Nutrition CoQ10 200 mg

NOW Ubiquinol CoQH-CF 50 mg

Solgar Ubiquinol 100 mg


I hope this is helpful.

Edited by Kathrynne Holden, MS
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i have a concern with ALA, it is a weak chelator, it passes the BBB and theoretically it could redistribute mercury and other metals from amalgams into the brain.


does carnitine compete with L-DOPA for transport into the blood from the small intestine and also across the BBB?  That might be an issue in timing.


Appreciate your posting the article.

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Great questions!


Regarding ALA, in theory that could be true; however, in animal studies ALA has been shown protective in a number of circumstances. Here are a couple:


Mol Cell Biochem. 2010 Nov;344(1-2):231-9. doi: 10.1007/s11010-010-0547-x. Epub 2010 Aug 5.
Neuroprotective role of lipoic acid against acute toxicity of N-acetylaspartic acid.
Pederzolli CD1, Rosa AP, de Oliveira AS, Coelho JG, Becker Dda L, Dalazen GR, Moraes TB, Dutra-Filho CS.
Author information

N-Acetylaspartic acid (NAA) accumulates in Canavan disease, a severe inherited neurometabolic disorder clinically characterized by mental retardation, hypotonia, macrocephaly, and seizures. The mechanisms of brain damage in this disease remain poorly understood. Recent studies developed by our research group showed that NAA induces oxidative stress in vitro and in vivo in cerebral cortex of rats. Lipoic acid is considered as an efficient antioxidant which can easily cross the blood-brain barrier. Considering the absence of specific treatment to Canavan disease, this study evaluates the possible prevention of the oxidative stress promoted by NAA in vivo by the antioxidant lipoic acid to preliminarily evaluate lipoic acid efficacy against pro-oxidative effects of NAA. Fourteen-day-old Wistar rats received an acute administration of 0.6 mmol NAA/g body weight with or without lipoic acid (40 mg/kg body weight). Catalase (CAT), glutathione peroxidase (GPx), and glucose 6-phosphate dehydrogenase activities, hydrogen peroxide content, thiobarbituric acid-reactive substances (TBA-RS), spontaneous chemiluminescence, protein carbonyl content, total antioxidant potential, and DNA-protein cross-links were assayed in the cerebral cortex of rats. CAT, GPx activities, and total antioxidant potential were significantly reduced, while hydrogen peroxide content, TBA-RS, spontaneous chemiluminescence, and protein carbonyl content were significantly enhanced by acute administration of NAA. Those effects were all prevented by lipoic acid pretreatment. Our results clearly show that lipoic acid may protect against the oxidative stress promoted by NAA. This could represent a new therapeutic approach to the patients affected by Canavan disease.

Neurochem Int. 2012 Dec;61(7):1231-41. doi: 10.1016/j.neuint.2012.09.003. Epub 2012 Sep 17.
The oxidative damage and inflammation caused by pesticides are reverted by lipoic acid in rat brain.
Astiz M1, de Alaniz MJ, Marra CA.
Author information

We have previously demonstrated that the administration of low doses of dimethoate, glyphosate and zineb to rats (i.p. 1/250 LD50, three times a week for 5weeks) provokes severe oxidative stress (OS) in specific brain regions: substantia nigra, cortex and hippocampus. These effects were also observed in plasma. Lipoic acid (LA) is considered an "ideal antioxidant" due to its ability to scavenge reactive species, reset antioxidant levels and cross the blood-brain barrier. To investigate its protective effect we administered LA (i.p. 25, 50 and 100mg/kg) simultaneously with the pesticide mixture (PM) for 5weeks. After suppression of PM administration, we evaluated the restorative effect of LA for a further 5weeks. LA prevented OS and the production of nitrites+nitrates [NOx] caused by PM in a dose-dependent manner. The PM-induced decrease in reduced glutathione and ?-tocopherol levels in all brain regions was completely restored by LA at both high doses. PM administration also caused an increase in prostaglandins E(2) and F(2?) in brain that was reduced by LA in a dose-dependent fashion. Taking into account the relationship between OS, inflammation and apoptosis, we measured caspase and calpain activity. Only milli- and micro-calpain isoforms were increased in the PM-treated group and LA reduced the activities to basal levels. We also demonstrated that interrupting PM administration is not enough to restore the levels of all the parameters measured and that LA is necessary to achieve basal status. In our experimental model LA displayed a protective role against pesticide-induced damage, suggesting that LA administration is a promising therapeutic strategy to cope with disorders suspected to be caused by OS generators, especially in brain.



Regarding Acetyl-L-Carnitine, yes, it is an amino acid; however the amino acids of concern are the large neutral aminos leucine, isoleucine, valine, phenylalanine, tryptophan, tyrosine, methionine, and histidine. These utilize the same carriers in the small intestine as levodopa, and do compete with levodopa for absorption. Thankfully, acetyl-l-carnitine is not among these, you would not need to worry about timing.

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So in addition to all this, I gotta take vitamin D, zinc, fish oil, plus eat walnuts, blueberries, coconut oil, cinnamon......I'm stuffed, and I haven't even eaten breakfast! :-P

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LOL ! -- Well, I've never said weight gain would be EASY. No pain, no gain, as they say. :lol:

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thanks for your research, especially on AA competition with l-dopa, but ALA still would concern me since mice do not have metals in their mouth and it seems possible that continuous low doses of ALA may redistribute metals into the brain rather than remove them.  my concern may be entirely unfounded.  here's a reference on "do it yourself" chelation by andy cutler



this may be much ado  about nothing.

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You may be right about ALA. It has been so heavily studied in humans that it seems to be generally regarded as safe, but that isn't always the case -- and also, individual reaction may vary. You might post your question to Dr. Okun, for another opinion.

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Regarding the original study in this post, I don't know about the other supplements, but I have read that melatonin is not necessarily good or safe to take for long term. What do you know about this specifically?

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As far as I can tell there haven't been any long-term studies testing its safety for those with PD. It is generally regarded as safe when used in recommended doses (often this is 3 mg per day) in the short term. And there is an interesting Russian study that I would like to have in its entirety, but unfortunately only have the abstract:


Zh Nevrol Psikhiatr Im S S Korsakova. 2013;113(7 Pt 2):77-81.

[The use of melatonin in the treatment of chronic fatigue syndrome and circadian rhythm disorders in Parkinson's disease].
[Article in Russian]


Chronic fatigue syndrome (CFS), a specific asthenic condition, is identified in a half of patients with Parkinson's disease (PD). An aim of the study was to evaluate an effect of melatonin (melaxen) on the severity of CFS, affective disorders, quality of life and sleep disorders in 30 patients with early and late stages of PD. After treatment, there was a decrease by 21% (p<0,05) on the Parkinson fatigue scale. At the same time, the improvement of sleep, assessed by the PDSS, decrease in the state anxiety on the Spilberger's scale and improvement of quality of life on the PDQ-39 (p<0,05) were found. No significant differences in motor, cognitive autonomic disorders and depression level were noted compared to baseline. Therefore, melatonin, together with optimized antiparkinsonian treatment, can treat CFS, improve sleep and quality of life of PD patients.




So, my best answer is that so far I don't have data to say that long-term use is safe. I would discuss it with my neurologist and if s/he agreed, would probably give it three to six months, journaling any notable effects, good or bad.

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I am actually seriously considering this protacol. I have been exchanging emails with the author and it sounds reasonable . I plan on sharing his article with both my pcp and neurologist. I don't have any expectation tat they will agree, doctors sometimes can't look outside the box.

I am bit sure you can't answer this ? Openly in this forum if not perhaps you could answer privately. Given your experience and knowledge of pd and your expertise in the nutrition field. If you had pd would you try this?

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I have a strong tendency to use myself as my own personal guinea pig, keeping a journal of how a substance or lifestyle change affects me. So yes, I very likely would try this protocol, journaling my reactions if any, both positive and negative.


But I would not recommend that others follow my example. I would, however, definitely print the article and discuss it with your neurologist and PCP -- you never know until you ask!

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OK so I saw my neurologist yesterday and he said that folowing this procedure shouldnt hurt me.  He was actually very nice about it. I expected a scientific approach..... hasnt been studied ect ect.  Now I am interested in finding reliable supplements at a cheap price.  Any suggestions?

 You had given me a list before but I need Acetyl-L-carnitine in 250mg tabs

Any thoughts about where I can order or get reliable supplements?

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I generally check ConsumerLabs (an independent testing agency) for quality products. There were none shown that had 250 mg, but here are some that were listed:


Bluebonnet Acetyl-L-carnitine 500 mg

Doctor's Best Acetyl-L-carnitine 500 to 2000 mg

GNC Acetyl-L-carnitine 500 mg

Jarrow Formulas Acetyl-L-carnitine 500 mg

Vitacost HCL Acetyl-L-carnitine 500 mg


I don't know why they are not made in smaller amounts.

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Here are two that offer brands tested by ConsumerLabs, and have various discounts, sometimes free shipping, or other offers; but I have no personal knowledge of the companies themselves, and do not endorse them.





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It's probably my brain playing tricks on me again, but I'm having a hard time visualizing a time schedule for taking the supplements recommended in this protocol.  Could you clarify a bit for me?


First, as to item number 2:  (a) Does the protocol propose taking between 200-400 mg of Alpha Lipoic Acid and 250-500 mg of Acetyl-L-Carnitine with every meal (three times each day) (plus 250 mg of Acetyl-L-Carnitine at bedtime as noted in number 5)?   (B) What does the protocol mean by "in divided doses for higher dose?"  How much?  When?  I have read that as a supplement for weight training and athletic improvement, Acetyl-L-Carnitine seems to have its best response between 2,000 mg and 3,000 mg per day.  Even taking 500 mg, three time per day, plus 250 mg at bedtime, would put me under that range, so what dose would get divided?   ©  What would a sample dose and time schedule for these supplements look like?


Second, as to item number 3:   (a)  What is a divided dose of Co-10 and when would I take each?  Does this protocol recommend takeing Co-Q10 three times per day in equal doses, starting at 200 mg per day maximum (66.66 mg per dose), or is it recommending taking Co-Q10 twice a day at 100 mg each and then increasing to 800 mg max (400 mg twice a day)?   (B)  If Co-10 helps the body use Melatonin, Acetyl-L-Carnitine and Alpha Lipoic Acid, is it best to take Co-Q10 each time one of the other supplements is taken or does one dose taken once a day with Vitmain E cover the body's needs for 24 hours?  ©  Do I take Co-Q10 with food or not?


Thanks for your help.

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I have seen both my MDS and PCP and was very pleasantly surprise by their reaction to this approach. Both said to go ahead they didnt think it would hurt me and my PCP who has PD himself is going to try it.  I have a few supplement ?

Is it safe to assume that if Jarrow Acetyl-l-carnitine 500mg is approved by consumer labs that the 250mg version is ok?

Could you check consumer labs for any suggestions re:Circadin 2 mg slow release?

What is the difference between Q10 and Ubiquinol


You are such an important resource!!


THank you

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