See also: MitoQ--a mitochondria-targeted antioxidant that aims to address CoQ10's inefficiencies.
https://pubmed.ncbi.nlm.nih.gov/17642004/
MitoQ is an orally active antioxidant that has the ability to target mitochondrial dysfunction. The agent is currently under development by Antipodean Pharmaceuticals Inc in phase II clinical trials for Parkinson's disease and liver damage associated with HCV infection. MitoQ has demonstrated encouraging preclinical results in numerous studies in isolated mitochondria, cells and tissues undergoing oxidative stress and apoptotic death. MitoQ aims to not only mimic the role of the endogenous mitochondrial antioxidant coenzyme Q10 (CoQ10), but also to augment substantially the antioxidant capacity of CoQ to supraphysiological levels in a mitochondrial membrane potential-dependent manner. MitoQ represents the first foray into the clinic in an attempt to deliver an antioxidant to an intracellular region that is responsible for the formation of increased levels of potentially deleterious reactive oxygen species. Results from the clinical trials with MitoQ will have important repercussions on the relevance of a mitochondrial-targeted approach.
Mitoq failed as a therapeutic option for primary mitochondrial disease. Now, it is sold OTC. As a patient with primary’s mitochondrial disease I have tried mitoq several times. Other than placebo effect, it did not work for me
There isn't a yes/no answer for this. The disease has no cure and it is progressive, so saying that it worked for me means that it helps me in my day-to-day (fatigue level, vitality, post-exercise recovery, etc), but that's it. I understand that this is highly subjective from the outside, but after trying hundreds of different things I have developed a sixth sense to know what works for me.
The most important thing is food. In my case, a lowish-carb diet (around 100 grams/day). Only tubers and rice. I also do 2 keto cycles of 4-6 weeks every year based on this study [1]. It is a pain to go through this, but it seems to do some good in the long run.
The second thing is exercise. A combination of weight training and HIIT works great. There is some science behind this. In short: satellite cells are mutation free. Weight training activates them and aerobics makes them "reproduce". This way, I can offset the replication advantage that mutant cells have ("clonal expansion", the force that makes the disease progressive).
Third, supplements.
Plain CoQ10 in some formulation that improve bio-availability (p.e. Jarrow's Q-absorb). 100-200 mg/day. I can't see additional benefits in larger doses.
Plain non-flush niacin (500 mg/day). There is a recent study for this [1] with actual human beings with the very same disease that I have.
I also take curcumin and several forms of magnesium daily. They both seem to work.
NMN (nicotinamide mononucleotide) and even just plain nicotinamide. Taking a large dose of nicotinamide (3g/day divided into 3 spaced-out doses) has resolved several relatively minor issues which I suspected were caused by some genetically caused mitochondrial deficiency. For example, I had some skin problems, including inflammation along the hairline, acne-like lesions on the neck and so-called "histamine intolerance" (inflammation-like red splotches). After a few weeks of taking nicotinamide all of these started clearing up and after a few months disappeared completely. Also I have higher and more even energy levels throughout the day.
One specific change that points at improved mitochondrial function is that I used to get shivering cold very easily, especially when wet. Not anymore! Just yesterday while walking for exercise I got surprised by a downpour and continued my walk soaking wet without any discomfort.
I’m going to have to look into this more. Thanks for sharing your experience. I’ve had a seemingly random skin rash that happens on my forehead and my neck and shoulders from time to time and I haven’t been able to figure out the cause of it, or even a name for it. It looks similar to pictures of what you describe as “histamine intolerance”.
Well, it's called histamine intolerance in the literature, but it's not really an intolerance in the sense of an allergy, it could more accurately called "excessive histamine build-up". The likely proximate cause is a deficiency in the enzyme (diamine oxidase) which breaks down excess histamine. This in turn has been linked to under-methylation, and mitochondria play a role in a lot of processes involving methylation. Alternatively, mitochondria are important in mitosis and cell-differenciation, and skin cells have a very short lifespan (high turn-over) so the skin is relatively sensitive to any kind of mitochondrial dysfunction. Yes, these are very vague connections, but what's very concrete is that taking nicotinamide has very visible and repeatable benefits for me, including eliminating the "histamine intolerance".
>> This in turn has been linked to under-methylation, and mitochondria play a role in a lot of processes involving methylation.
Do you mean epigenetic methylation?
As the cellular reprogramming techniques for example strive to reverse the current pattern of epigenetic methylation.
DAO deficiency can be a consequence of Copper deficiency, as DAO is a Copper enzyme.
Copper deficiency used to be considered rare, but give the rise in popularity of Zinc which prevents Copper and absorption and depletes Copper stores, it has bevone more common.
Hives is what that is, they come up in the evening. My cure was clearing yeast. One sneaky source is from those slightly fancy lettuce that sandwiches or meals often come from. Avoid that and all non organic bread. Work to heal your gut as it gets into the body from leaky gums and leaky gut.
PQQ (together with CoQ10), all B vitamins (B1 for Krebs cycle coenzymes, B2 for FAD+, B3 for NAD+), Niagen/NMN for NAD+, Acetyl L-Carnitine, R Alpha Lipoic Acid, Alpha-Ketoglutarate, AXA1125 for mitochondrial dysfunction (i.e. BCAA + glutamine + NAC + Arginine) etc.
Oral supplementation has low efficiency, but taking higher doses can compensate.
There are some formulations that purport to have higher bioavailability on a gram-for-gram basis according to trials, but their price is often high enough that it’s cheaper to take more of a generic CoQ10 than to buy an expensive formulation.
CoQ10 supplementation has resulted in insomnia for some. I triggered it with higher doses (600-900mg per day) before I realized what was happening. Dropping down to 300mg alleviated the insomnia after about a week, which I interpreted as meaning the supplement was doing something.
>> There are some formulations that purport to have higher bioavailability on a gram-for-gram basis according to trials, but their price is often high enough that it’s cheaper to take more of a generic CoQ10 than to buy an expensive formulation.
Isn't bioavailability ensured mainly by a liposomic form? Sinclair mentioned in podcasts that he is taking for example 1 gram of resveratrol with a pinch of jogurt (=fat) to increase bioavailability.
If you take a powder form capsule with a pinch of olive oil, shouldn't it increase its bioavailability? (to cheaply emulate a liposomic form)
I've bought a bunch of stuff of Bryan Johnsons supplement list (a reasonable amount, 8-9/day) and he recommends 100mg, not sure if he's researched that one properly but he's usually pretty open about it https://blueprint.bryanjohnson.co/#step-2-supplements
Strangely enough he is taking NR (nicotineamid riboside) rather than NMN, probably as there was recent evidence (including on HN) that NMN can evoke cancer (in those who are prone to cancer or already have it).
There are supplement formulations that are supposed to improve absorption, but I don’t know of their efficacy.
AFAIK heavy front end loading is the only current option and may have limited effectiveness, although empirically I can say that supplementation appears to reduce markers of oxidative stress in my bloodstream and is similar but less effective for my brother, and it seemed effective for my father. I have a suspicion that absorption might have a genetic component or may be dependant on other lifestyle factors, or perhaps dependant upon the generation mechanisms for oxidative stress itself.
IOTW YMMV and I’m not sure if supplemental CoQ10 is effective for everyone. It does seem to be safe, though, so there’s that.
I have no reason to believe that one brand is categorically better than another so I typically buy from someplace like puritans pride because of cost. Seems to work. From the website it’s cheaper than if you buy from their Amazon store.
But I wouldn’t call this a recommendation, more if a report of my choice and my reasoning.
I’m sure there are “better” options, but I don’t care if I have to ingest 200 mg of one brand to get the benefit I would get from 100mg of another brand, for 4x the price. In all I’d rather buy from a source that moves a lot of production and is less likely to be counterfeited or suffer from production inconsistencies.
But that’s just like, my unfounded and poorly considered opinion so…
I'll second the recommendation for Nootropics Depot. They're top notch with regard to testing (they run an ISO 17025 accreddited lab), and the owner frequently talks about the science of how various compounds work and interact on r/NootropicsDepot.
Animal organ meats, especially hearts, have the highest level of CoQ10 of any common dietary sources. I suspect quite a few common modern dietary deficiences are the result most people no longer eating the "whole animal".
ubiquinol is the reduced "active" form of coq10 ubiquinone and while ubiquinol can be much more expensive, studies seem to indicate in people older or ill where nutrition absorption may be far less than ideal, the "active" form is absorbed better
But like all FUD in the supplement industry, you do not need mega doses
I've probably already had that when consuming gram amounts of calcium carbonate.
The body's ability to recover is underrated.
The ECG's used by ambulance staff should be able to pick up the minute murmur in heart attacks, well having experienced something that could be described as one, highlights the vagaries in medical descriptions and the inability of portable ECG's to detect such a thing.
Little short of losing a limb, there's not much I havent been through, but the Police demonstrated their criminality years ago. Taxpayer funded entities in the UK, put the Nazi's to shame in terms of ingenuity.
I love conspiracy theories and conspiracy facts but I doubt that it’s big surgery lobby not wanting people to be more clotty. Bad Blood clots aren’t that uncommon, at all. Can be dangerous or not but they not rare by any means. I’m also not convinced on your mega dose theory.
That said, wanted to share that super glue was used in Vietnam War to close wounds. Also dermabond RX is krazy glue [1].
Also, this month I’ve caught and killed 12 raccoons. Not sure if you have them over there but they are vile disgusting disease vectors but very cute looking.
> I love conspiracy theories and conspiracy facts but I doubt that it’s big surgery lobby not wanting people to be more clotty.
View it however you like, the saying "you can lead a horse to water, but you cant make it drink" springs to mind, but do these two aforementioned chemicals only do blood clotting, or do they take part in other chemical reactions which may be good or bad for human health?
> Also, this month I’ve caught and killed 12 raccoons. Not sure if you have them over there but they are vile disgusting disease vectors
Dont know if you noticed but living on an island has meant alot of the dangerous animals and vectors were eradicated hundreds of years ago in the UK, and yet in a schadenfreude like manner, the UK and royals like Prince Philip and King Charles attempt to lead the world in animal conservation elsewhere in the world. The Frenchie called William The Conqueror had his uses!
That must annoy the Aussies amongst others, considering how many dangerous animals they have over there, but they do put up a good Monty Python Black Knight attitude to the situation.
https://www.youtube.com/watch?v=SI5nL8vZcl8
Most of the body’s daily requirement for CoQ10 is produced within the body. Some CoQ10 is ingested from food (typically 5 mg/day [5]). It is estimated that the daily requirement for CoQ10, from both endogenous bio-synthesis and food sources, is about 500 mg; this estimate is based on a total body quantity of about 2 mg of CoQ10 and based on an average turnover time of 4 days in tissue [5]. This estimate serves as the justification for the size of the dosage (typically 300 mg/day) that is used in many clinical trial studies.
As people mature into adulthood and begin to increase in age, the ability of the body to synthesise its own CoQ10 decreases; optimal human bio-synthesis occurs in the mid-twenties, with a continual gradual decline in tissue levels thereafter [6]. In addition to the normal aging process, CoQ10 levels have also been shown to be depleted in a number of disorders, particularly heart disease [7]. The synthesis of CoQ10 is a complex multistage process (governed by at least 13 genes), requiring a number of amino acids, vitamins, and trace element precursors and cofactors, deficiency of any of which can adversely affect normal CoQ10 production [8]. Nutritional supplementation with CoQ10 therefore provides a mechanism to maintain adequate levels within the body.
...The CoQ10 raw material comes in the structural form of polymorphic crystals [9]. CoQ10 in polymorphic crystalline forms will not be absorbed in the gastro-intestinal tract. CoQ10 can be absorbed only as individual molecules, as described in Section 4 of this article below [10]. The CoQ10 crystals must therefore be dissociated first into individual CoQ10 molecules.
...The first point of note is the difference in bioavailability between samples 01 and 02 of the study. Both samples contained 100 mg CoQ10 in identical ubiquinone form, in a soy carrier oil with identical excipient content and capsule specification; sample 01 (Myoqinon, Pharma Nord, Vejle, Denmark) had been subject to a patented thermal crystal dispersion process whilst sample 02 (from the same manufacturer) had not undergone this procedure. The respective mean AUC and Cmax values in the Lopez-Lluch study were 28.0 mg/L/48 h and 1.07 mg/L for sample 01, and 6.89 mg/L/48 h and 0.33 mg/L for sample 2. Failure to subject crystalline CoQ10 to crystal dispersion therefore reduced bioavailability by approximately 75%.
...Thus, the AUC for CoQ10 in ubiquinol form was approximately twice of that for ubiquinone, which had not been subjected to thermal crystal dispersion (sample 02), but was only 52% of that for ubiquinone that had been subjected to thermal crystal dispersion (sample 01). It should be noted that it is not possible to subject ubiquinol to the same crystal dispersion process as that described for sample 01; this is because of the differential stability of ubiquinone and ubiquinol. These data therefore demonstrate (i) the importance of CoQ10 crystal dispersion, the absence of which reduces bioavailability by some 75%; (ii) the fact that the relative bioavailability of ubiquinone and ubiquinol forms of CoQ10 depends on CoQ10 crystal dispersion status and carrier oil/excipient composition.
... The study therefore concluded that intestinal absorption of CoQ10 is highly variable among individuals, and is independent of the form of CoQ10 (ubiquinone/ubiquinol) administered. This is because the body is limited in how much CoQ10 it can absorb at a given time, and thus if an individual takes several 100 mg capsules together, some of the CoQ10 tends to be wasted
CoQ10 is a lipid soluble substance; therefore, the highest quality CoQ10 preparations have the CoQ10 dissolved in a well-suited carrier lipid (e.g., soy oil or palm oil).
The KISEL-10 study was a clinical trial that enrolled 443 senior citizens living in south-eastern Sweden. The study was designed as a randomized, double-blind, placebo-controlled clinical trial. The elderly study participants—average age of 78 years—took either 200 milligrams of coenzyme Q10 together with 200 micrograms of an organic high-selenium yeast preparation or matching placebos daily for 4 years
The cardio-protective effect of the combined daily supplementation with CoQ10 and selenium endure for several years beyond the period of intervention. A follow-up analysis showed that the significantly reduced risk of death from heart disease still held 12 years after the intervention
(Every solid potential benefit is larded through with how inconclusive the studies are. The only thing they're willing to actually say is that CoQ10 is probably harmless. I couldn't even find that much about CoQ4.)
https://pubmed.ncbi.nlm.nih.gov/17642004/ MitoQ is an orally active antioxidant that has the ability to target mitochondrial dysfunction. The agent is currently under development by Antipodean Pharmaceuticals Inc in phase II clinical trials for Parkinson's disease and liver damage associated with HCV infection. MitoQ has demonstrated encouraging preclinical results in numerous studies in isolated mitochondria, cells and tissues undergoing oxidative stress and apoptotic death. MitoQ aims to not only mimic the role of the endogenous mitochondrial antioxidant coenzyme Q10 (CoQ10), but also to augment substantially the antioxidant capacity of CoQ to supraphysiological levels in a mitochondrial membrane potential-dependent manner. MitoQ represents the first foray into the clinic in an attempt to deliver an antioxidant to an intracellular region that is responsible for the formation of increased levels of potentially deleterious reactive oxygen species. Results from the clinical trials with MitoQ will have important repercussions on the relevance of a mitochondrial-targeted approach.
See also also: SkQ Skulachev Ions https://en.wikipedia.org/wiki/SkQ