CoQ4 is a functional substitute for CoQ10 and can be targeted to mitochondria
biorxiv.org
biorxiv.org
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
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.
[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5090656/ [2] https://doi.org/10.1016/j.cmet.2020.04.008
A. Other mitochondrial helping supplements
B. Forums which discuss such things?
I’ll start - I’ve heard good things about ALCAR, citrulline and d-ribose. Reddit’s r/nootropics is my preferred answer to B.
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.
Do you mean epigenetic methylation? As the cellular reprogramming techniques for example strive to reverse the current pattern of epigenetic methylation.
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.
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.
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…
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.
I've suffered from Longcovid since last year, and this seems to be something safe that I can try, with a possibility of positive result.
I will try 200-300mg instead
I'm not as old as him nor trying to do anti aging. Being >50 has different requirements.
I'm just healthmaxxing
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)
But like all FUD in the supplement industry, you do not need mega doses
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
Other than that, "more studies are needed":
https://health.clevelandclinic.org/what-is-coq10/
(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.)