The Lowdown on CoQ10 and Ubiquinol Supplementation


This blog post is a companion to a video. To watch the video, click here.


A coenzyme is a small molecule that cannot by itself catalyze a reaction but can help enzymes to do so. Vitamins B1, B2, and B6 are coenzymes, for example.


First isolated in bovine mitochondria in 1957, Coenzyme Q10 (1,4-benzoquinone), also called ubiquinone because it is found in virtually every cell in the human body, henceforth, CoQ10 is an essential lipid component of the mitochondrial electron transport chain (ETC), which is present in the inner mitochondrial membrane. It is found in highest concentrations in tissue with high-energy turnover, like the heart, brain, liver, and kidneys[1]. It is produced de novo in humans and is produced by all cells. It is composed of an isoprene chain that contains more subunits in more developed animals (e.g. E. coli have CoQ8, mice have CoQ9 and CoQ10, we have CoQ10).


There, CoQ10 transports electrons from complexes I and II to complex III to provide energy for proton translocation to the intermembrane space[2]. Its presence is necessary for cellular respiration and ATP production.


These ETC complexes are efficiently organized into respiratory complexes to limit electron leakage to oxygen, which would result in the development of reactive oxygen species. Mitochondrial CoQ10 may associate in discrete groups dedicated to either NADH-coupled or FADH2-coupled electron transport[3].


Mitochondrial complex I depends on the CoQ redoxc state[4]; the reduced from of CoQ (CoQH2) produces complex I-specific ROS production that extends life in small organisms[5]. Other mitochondrial activities, such as the dihydroororate dehydrogenase, beta-oxidation of fatty acids, and mitochondrial glyecerol-3-phosphate dehydrogenase, also increase the synthesis of CoQH2[6].


CoQ10 is a scavenger of free radicals produced during oxidative phosphorylation of the inner mitochondrial membrane. It also provides antioxidant protection to all cell membranes and plasma lipoproteins. It has been proposed that the ratio of NAD(P)H:quinone oxidoreductase q (NQO1) functions as a redox-sensitive switch to regulate the response of cells to changes in their redox environment[7].


DEFICIENCY


1. Very rarely, heterogenous genetic conditions concerning COQ genes or genes involved in mitochondrial functions can produce CoQ10 deficiency[8]. Symptoms of CoQ10 deficiency are varied (eyes, hearing, kidney function, ataxia, etc.), though a muscle or skin biopsy can easily diagnose the condition.


THE BRAIN


1. A water-soluble version of CoQ10 called Ubisol-Q 10 was used to potently inhibit the development of Alzheimer’s disease among transgenic rodents[9].

2. A nanoemulsion of CoQ10 (that was 80% more bioavailable) was also used to slow the progression of Parkinson’s disease among rodents[10].

3. MitoQ (a branded, absorbable form of CoQ10) was shown to sharply reduce disease progression in a rodent model of ALS.


STEROIDOGENESIS


1. While supplementing CoQ10 does not improve steroidogenesis, it does protect animals from declines in steroidogenesis after exposure to chemical toxicants, likely due to its neutralization of free radicals[11].


OXIDATIVE STRESS


1. The antioxidant function of CoQ10 is integral to maintaining the integrity of the plasma membrane, which it does by reducing vitamins C and E, and by preventing ceramide-mediated apoptosis[12].

a. Ceramide-mediated apoptosis is a regulator of the lifespan of animals[13][14].

2. A meta-analysis of 17 studies found that supplementation with CoQ10 did not alter nitric oxide level, glutathione, catalase activity, or glutathione peroxidase activity. However, it did decrease malondialdehyde and increase total antioxidant capacity (TAC)[15].

3. Patients with Down syndrome have naturally low CoQ10 levels and high pro-inflammatory cytokine expression. A team of Italian researchers has discovered that treatment with CoQ10 reduced the pro-inflammatory status of the patients and reduces the rate of DNA damage[16].

4. In those who have diseases associated with hyperactive immune systems, CoQ10 supplementation (up to 500 mg/day) significantly reduced C-reactive protein (CRP), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-a) – 2 of the most damaging pro-inflammatory cytokines[17].

5. In another study, supplementing with CoQ10 most significantly reduced IL-6 levels[18].

6. In metabolic disease, while CRP and IL-6 may not be reduced, tumor necrosis factor alpha (TNF-a) is lowered by CoQ10 supplementation[19].

7. In rheumatoid arthritics, supplementing 100mg/day of CoQ10 lowered plasma TNF-a levels[20].

8. While CoQ10 supplementation does not lower CRP, it does lower TNF alpha levels in humans[21].


CARDIOVASCULAR DISEASE


1. In the Q-SYMBIO trial, 300mg of CoQ10 given to 420 patients suffering from chronic heart failure over a two-year period significantly improved symptoms and reduced cardiac events[22].

a. Later, it was show that the treatment increased the elderly cohorts IGF-1 and IGFBP-1[23].

2. Over a 4-year treatment period, a large Swedish cohort exhibited less cardiovascular mortality not only during the trial period but also 10 years later, when given CoQ10 and selenium[24].

3. Low dose CoQ10 monotherapy reduced systolic blood pressures[25].

4. CoQ10 lowers lipid peroxidation of LDL particles by encouraging vitamin E (alpha tocopherol) to act as an anti-oxidant to LDL particles rather than a pro-oxidant[26].

5. Prophylactic treatment with CoQ10 pre-cardiac surgery improved patient outcomes, specifically reducing the need for ionotropic drugs post-surgery and reducing the rates of arrythmias[27].

6. A 12-week trial showed that CoQ10 supplementation reduced serum triglycerides in diabetic patients[28].

7. Shocking, CoQ10 supplementation has been shown to lower lipoprotein (a) but not other lipid metrics (other than triglycerides, in diabetics)[29].

8. CoQ10 supplementation significantly but minorly reduces systolic blood pressure in people with metabolic diseases[30].

9. CoQ10 has been shown to attenuate left ventricular remodeling following myocardial infarction, potentially due to its reduction in angiotensin-converting enzyme (ACE)[31].

10. A meta-analysis found that patients with heart failure had lower mortality and higher exercise capacity after supplementing with CoQ10[32].


STATINS


Statins impair HMG-CoA reductase, the enzyme involved in the synthesis of cholesterol as well as the synthesis of CoQ.


1. Myopathy due to statins is thought to be due to a reduction in CoQ10 and selenoprotein levels[33], in fact, supplementation with CoQ10 and selenium reverses some of the myopathy[34].

2. CoQ10 supplementation has been shown to improve endothelial dysfunction in type 2 diabetics treated with statin[35]s.

3. CoQ10 supplementation has been shown to reverse the worsening of left ventricular diastolic function induced by statins[36].


KIDNEYS


1. Although it is unclear whether antioxidants can reduce the progression of chronic kidney disease[37], rodent studies show the reduced form (ubiquinol) has a protective effect on kidney disease.

2. Among patients undergoing dialysis, those given 1200 mg of CoQ10 exhibited lower F2-isoprostane in their plasma, indicating lower oxidative stress[38].


AGING


1. Transgenic mice lacking one allele of the COQ7 gene are exceptionally long-lived despite having average CoQ10 levels[39].

2. In a model of transgenic, senescence-prone mice (samp1), mitochondrial levels of CoQ10 associated positively with longevity[40].

3. Supplementing with the reduced form (ubiquinol) has been shown to reduce senescence in rodents[41].

4. CoQ10 has been shown to counteract telomere shortening and extend lifespan in stressed, small organisms[42].

5. Supplementation with CoQ10 and selenium in elderly Swedes significantly increased IGF-1 and IGFBP-1 levels, potentially explaining its protective role on cardiovascular morbidity[43]. Note that increasing protein consumption past the age of 60, as recommended by Valter Longo, is mainly due to this need for increased IGF-1[44]. Fascinatingly, ACE inhibition increases IGF-1 levels in the elderly[45].


THE ELDERLY


1. Among the elderly, concentrations of CoQ10 in plasma are associated with physical activity, cholesterol concentrations, and lower lipid oxidative damage[46].

2. Elderly people given CoQ10 and selenium over a 4-year-period exhibit improvements in quality of life[47].


FERTILITY


1. CoQ10 levels in seminal fluid are considered a marker of the health of sperm[48], as oxidative stress is among the major determinants for the health of sperm.

2. Supplementation with CoQ10 has been shown to improve semen and sperm parameters across studies[49][50][51].


SUPPLEMENTATION


1. The EU has approved the reduced from of CoQ10 (CoQ10H2) for the treatment of primary CoQ10 insufficiency, although patients with secondary insufficiency may fail to respond[52].

2. In horses, 1g of ubiquinol increased plasma CoQ10 concentrations 2-5x, and levels persisted for 2 weeks after discontinuation. The effects on semen quality persisted for 4 weeks after discontinuation[53].


MitoQ


1. MitoQ is ubiquinol attached to a lipophilic triphenylphosphonium cation. The cation is intended to allow ubiquinol to enter the mitochondria of the cell. The cited study shows that certain MitoQ variants (e.g. those with a 15 carbon aliphatic chain) are better able to enter the mitochondria than others[54].

2. It is thought that MitoQ’s effects are mostly due to the antioxidant action of quinol in the mitochondria. It is effective against lipid peroxidation but likely not effective against hydrogen peroxide. At very high doses, toxicity has been shown in mice. Interestingly, long-term administration of MitoQ in mice does not cause a consequent adaptive reduction in endogenous antioxidant gene expression, and is also not converted to the pro-oxidant superoxide in vivo[55].


DOSING


1. CoQ10 appears to be safely tolerated in humans a high as 2.4 grams per day[56]. Doses as high as 3g have been used for shorter trials[57].


RECOMMENDATIONS

1. For ubiquinol, consider Qunol Mega CoQ10 Ubiquinol: https://amzn.to/3ioyV7p

2. For MitoQ: https://amzn.to/3queRUe

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