Effects of coenzyme Q10 in early Parkinson disease: evidence of slowing of the functional decline

[SilentEchoes]

I've been doing a deep dive on mitochondrial DNA and the electron transport chain of the mitochondrial complex. I tested my mtDNA and I have a deficiency of the supercomplex II and III, this is a defect in the Krebs/TCA (citric acid) cycle.

If you're taking statins you might want to reevaluate this decision. “Mitochondria and the Future of Medicine” a chapter on mitochondrial involvement in neurodegeneration provides evidence that statins may be causal in many serious diseases such as ALS/MND, Parkinson’s Disease, Alzheimer’s disease, MS, etc. Statins block mevalonate synthesis, they lower levels of CoQ10, an essential compound for mitochondrial energy production, as well as lowering cholesterol. M. Flint Beal, a prominent neurologist, has spent years proving that CoQ10 has neuroprotective properties that might help diseases such as Parkinson’s and Huntington's and a growing body of scientific evidence supports his hypothesis. Research has established that mitochondria from platelets in patients with early, untreated Parkinson’s had reduced activities of Mitochondrial Complexes I, II and III.

There are conflicting opinions about CoQ10 supplementation. It's unlikely to harm you even at a higher dose of 1200 mg/d. Ubiquinol (CoQ10) is used in the ETC of mitochondria.

pubmed.ncbi.nlm.nih.gov/123...

[kevowpd]

might help diseases such as Parkinson’s and Huntington's and a growing body of scientific evidence supports his hypothesis

Really? Because a very high quality (n=600, basically unheard of in the PD world) study indicated that this wasn't the case at all.

jamanetwork.com/journals/ja...

[genesurf in reply to kevowpd]

Oh snap!

[chartist]

Yes, it has shown benefit in MSA also in this recent randomized double blind placebo controlled trial (May 2023) using 1500 mg/day of the more bioavailable form of CoQ10 called Ubiquinol :

ncbi.nlm.nih.gov/pmc/articl...

Here is a relevant quote from the RCT :

' Between June 26, 2018, and May 27, 2019, 139 patients were enrolled and randomly assigned to the ubiquinol group (n = 69) or the placebo group (n = 70). A total of 131 patients were included in the full analysis set (63 in the ubiquinol group; 68 in the placebo group). This study met the primary efficacy outcome (least square mean difference in UMSARS part 2 score (−1.7 [95% CI, −3.2 to −0.2]; P = 0.023)). The ubiquinol group also showed better secondary efficacy outcomes (Barthel index, Scale for the Assessment and Rating of Ataxia, and time required to walk 10 m). Rates of adverse events potentially related to the investigational drug were comparable between ubiquinol (n = 15 [23.8%]) and placebo (n = 21 [30.9%]). '

Considering that MSA response to CL is very poor at best, Ubiquinol seems worth considering and was well tolerated by the study participants.

Art

[Bolt_Upright in reply to chartist]

"Primary efficacy outcome

The LS mean changes in the UMSARS part 2 score from the baseline to 48 weeks were 5.4 in the ubiquinol group and 7.1 in the placebo group, which were significantly different (difference, −1.7; 95% confidence interval (CI), −3.2 to −0.2; P = 0.023) (Table 2 and Fig. 2A). The LS mean of the UMSARS part 2 score changes at each assessment (12, 24, 36, and 48 weeks) is shown in Fig. 2A and Table S1 in the Supplementary Appendix. Similar results were obtained in the PPS (Table S2 in the Supplementary Appendix)."

So... 1.7/7.1 = a 24% decrease in rate of decline?

Interesting charts:

UMSARS Charts

[chartist in reply to Bolt_Upright]

I find the dose and results interesting, given that nothing seems to move the needle much when it comes to MSA. It seems like if you have MSA, Ubiquinol should definitely be worth considering at a similar high dose and this is the highest dose of ubiquinol that I have seen used in humans and significantly higher than used in many older studies.

In MSA and PD, mitochondrial damage and or dysfunction is present and ubiquinol/CoQ10 is noted for restoring mitochondrial function and integrity. Melatonin also helps restore mitochondrial function and integrity in PwP at just 50 mg / day. Selenium is also mitochondrial beneficial. It seems reasonable to try and restore mitochondrial function in diseases where mitochondrial dysfunction is present. All three supplements have very good safety profiles at the respective dose that would be required.

MSA and PD have lower levels of CoQ10 in the cerebellar cortex while PwP also have lower CoQ10 levels in platelets and lymphocytes while patients with multiple system atrophy (MSA) showed decreased CoQ10 levels in the cerebellar cortex, serum/plasma, cerebrospinal fluid, and skin fibroblasts. Patients with Lewy body dementia (LBD) showed decreased cerebellar cortex CoQ10, and those with progressive supranuclear palsy (PSP) had decreased CoQ10 levels in the cerebrospinal fluid.

ncbi.nlm.nih.gov/pmc/articl...

Art

[Axter in reply to chartist]

You sure about "50" mg of melatonine?

[chartist in reply to Axter]

This is the PwP/melatonin study that used 50 mg of melatonin / day to improve mitochondrial function and return oxidative stress markers to healthy control levels :

hindawi.com/journals/omcl/2...

I take 132 mg/day of melatonin.

Art

[Sonshineman1 in reply to chartist]

Does that amount make you sleep a lot during the day

[chartist in reply to Sonshineman1]

No, that amount of melatonin doesn't, but I don't normally sleep during the day. When I first started high dose melatonin well over a decade ago, each time I increased my dose, it did make me sleepy the next day, but I am one of those that seems to adjust over a period of about two weeks or less, depending on how much I increase my dose. The highest I have gone is 180 mg/day.

Art

[Sonshineman1 in reply to chartist]

Thank you for that information

[Axter in reply to chartist]

In Italy I have never found melatonin preparations above 5mg.

[chartist in reply to Axter]

Yes, Europe generally offers melatonin as a prescription, in the US it is available over the counter from less than one mg up to 60 mg capsules that I am aware of. Here are some typical products :

amazon.com/s?k=60+mg+melato...

Art

[Shorebird in reply to chartist]

Hi Art,

Do you have a particular brand(s) of melatonin that you use/trust? In the US, since melatonin is available OTC / regulation of the ingredients can be an issue. Thank you!

[chartist in reply to Shorebird]

I don't have a brand that I would recommend. I have used many. I think Natrol is considered a good brand, but I have no idea what that is based on. My preference is for the type that dissolves in your mouth based mainly on the idea that melatonin can be absorbed at least partially through the mouth lining which may allow for better bioavailability while offering some protective effects to the mouth and esophagus. Melatonin normally has poor bioavailability estimated to be around 3% as discussed here :

ncbi.nlm.nih.gov/pmc/articl....

Here is a relevant quote :

' This cohort crossover study estimated pharmacokinetics of oral and iv melatonin, respectively in healthy volunteers. Bioavailability of oral melatonin was only 3 %. '

I think that melatonin may offer some of its benefits through gut microbiome manipulation which may at least partially explain how melatonin is able to do what it does at relatively low dose. If you figure that only 3% of your 50 mg dose is bioavailable, that is only 1.5 mg.

Art

[Shorebird in reply to chartist]

Thank you. 🙏🏼

[SilentEchoes in reply to Axter]

50 mg is the therapeutic dose. If you want to get crazy you can use suppositories at much higher dose. zetpilnutrition.com/product...

onlinelibrary.wiley.com/doi...

This article discusses melatonin in the 40-100 mg/dosage for AD and PD.

ncbi.nlm.nih.gov/pmc/articl...

I support this concept: Neurodegenerative diseases are chronic and progressive disorders characterized by selective destruction of neurons in motor, sensory, and cognitive systems. Despite their different origins, the majority of central and peripheral nervous system degenerative diseases (including Parkinson’s disease (PD), Alzheimer’s disease (AD), Huntington’s disease (HD), and amyotrophic lateral sclerosis) share the reduced capacity to maintain the balance between free radical formation and antioxidative mechanisms as a common critical factor.

link.springer.com/chapter/1...

I'm looking for the research article I read where melatonin suppository at a much higher dosage (500 mg- don't quote me) was shown to ameliorate MND. pubmed.ncbi.nlm.nih.gov/170...

This ties in nicely with my discussion of mtDNA damage in the electron transport chain in the mitochondrial complexes l-lV.

pubmed.ncbi.nlm.nih.gov/235...

It's my opinion (not medical advice) that coupling high dose melatonin with high dose CoQ10 would produce synergistic benefits.

pubmed.ncbi.nlm.nih.gov/356...

[chartist in reply to SilentEchoes]

I would tend to agree on the synergy aspect, but there is no study to confirm that idea.

Suppository melatonin was used in an ALS study years ago, and like the PD/melatonin study, it found that melatonin could return elevated oxidative stress levels to healthy control levels, which is important in both diseases.

Art

[SilentEchoes in reply to chartist]

They like to research one supplement at a time. There's the Healey study for ALS that's breaking this dogma.

[chartist in reply to SilentEchoes]

I have noticed in recent years a trend toward testing of more than one supplement at once to see if there is synergy between two supplements for a specific health issue. Here is an example :

ncbi.nlm.nih.gov/pmc/articl...

Here is a relevant study quote :

' These results identified a synergistic effect induced by combinational treatment with hesperidin and chlorogenic acid, which can regulate mitochondria and ATP production through the estrogen receptor pathway in MCF-7 cells. However, none of the treatments induced the generation of reactive oxygen species (ROS), suggesting that ROS likely plays no role in the observed pharmacological activities. Overall, our study sheds light on the adequacy of hesperidin and chlorogenic acid to serve as an adjunctive therapy when co-administrated with chemotherapy drugs in breast cancer patients. '

Melatonin + Andrographis/ Colorectal Cancer :

ncbi.nlm.nih.gov/pmc/articl...

A relevant study quote :

' RNA-sequencing analysis revealed candidate pathways and genes that mediated antitumor efficacy of MLT and Andro in CRC, among which autophagy pathway and related genes, including NR4A1, CTSL and Atg12, were found to be primarily responsible for the increased anticancer effect by the two natural products. In conclusion, our data reveal a potent and synergistic therapeutic effect of MLT and Andro in the treatment of CRC and provides a rationale for suppressing autophagy in cancer cells as a potential therapeutic strategy for CRC. '

Art

[chartist in reply to SilentEchoes]

This is the ALS study I was referring to that used 300 mg suppository melatonin in ALS patients for two years :

pubmed.ncbi.nlm.nih.gov/170...

Art

[Rustem]

Super interesting post. 🙏 May I ask you here, where I can do mitochondria DNA testing? And where is possible to get the explanation of the results?🙏❤️

[RonB1]

Where did you get tested for mtDNA?

[SilentEchoes]

mtDNA testing through Religen. It's called Mitoswab. I chose the 4x mtDNA. religendx.com/faq-mitoswab/