Coenzyme Q10
Ubiquinone
Coenzyme Q10 (CoQ10), also known as ubiquinone, is a naturally occurring anti-oxidant compound and is used for energy production within cells. It's manufactured in the heart, liver, kidney and pancreas. The body normally produces sufficient CoQ10, although some medications such as statins may interfere with this process and CoQ10 levels in the body may decline with age and heart disease. Only small amounts of CoQ10 are available from food, mainly beef and chicken. Consequently, dietary supplements are the most common way to increase the body's CoQ10 levels. After being absorbed into the body, more than 90% of CoQ10 is converted to its active form, known as (CoQH2-10) or ubiquinol. Ubiquinol has strong antioxidant properties. Conditions that cause oxidative stress on the body, like liver disease, decrease the ratio of ubiquinol to CoQ10.
In the body, blood levels of CoQ10 steadily rise from young adulthood through middle-age, peaking at around age 60, when levels then decrease — although they do not fall below levels of early adulthood. However, levels of CoQ10 in tissue of the brain, heart and pancreas do decrease with age. Perhaps of greater
significance though, is that, after age 60, the body seems to convert less CoQ10 into its active form (ubiquinol), resulting in a decreased ratio of ubiquinol to CoQ10 and indicating a higher level of oxidative stress.
Numerous conditions are now known to arise in which the body’s synthetic capacity is insufficient to meet CoQ10 requirements. Susceptibility to CoQ10 deficiency appears to be greatest in cells that are the most metabolically active, such as the brain and heart. Tissue deficiencies or subnormal serum levels of CoQ10 have been reported to occur in a wide range of medical conditions and decline with advancing age.
Given the central role of CoQ10 in mitochondrial function and cellular antioxidant protection, its clinical applications are extensive. There are many conditions where CoQ10 may offer benefit that there is little question that it should be considered a conditionally essential nutrient. The specific uses of CoQ10 include:
- General antioxidant
- Cardiovascular disease
- Cardiomyopathy
- Congestive heart failure
- Protection during cardiac surgery
- Hypertension
- Cancer
- Diabetes mellitus
- Male infertility
- Parkinson’s disease
- Friedreich’s ataxia
- Muscular dystrophy
- Immune function
Because of its role in enhancing immune function, CoQ10 has been considered as a possible anticancer agent. In one study, 32 women with breast cancer, who were classified as “high risk” because of tumor spread to the axillary lymph nodes, received 90 mg/ day of CoQ10, along with vitamins C and E, β-carotene, and essential fatty acids. In six of these women, the tumor became smaller. During the 18-month treatment period, none of the patients died (the expected number of deaths was four), and none showed signs of further distant metastases. Six patients had an apparent partial remission. In addition, patients receiving CoQ10 required fewer pain killers. In follow-up, a pilot study using this nutrient cocktail evaluated the survival of 40 patients with end-stage cancer over 9 years. Median survival of individuals receiving the CoQ10-containing nutrient cocktail was 40% longer than median predicted survival using the calculated Kaplan-Meier curve.
It is important to note that research in animals suggests that only a small amount of CoQ10 is actually absorbed, although it can still significantly increase CoQ10 blood levels. CoQ10, especially the dry dosage form (tablet or capsule), is best absorbed when fats or oils are present in the gastrointestinal tract , such as during a meal. The small amount of oil (typically less than 1 gram) in softgels and some other formulations may somewhat improve absorption, although not nearly as much as fat- or oil-containing meal, which could easily provide 5 to 40 grams of fats. If you see products marketed as "crystal-free" CoQ10 formulations, such as CoQsol-CF and Q-Best (Best Formulations), these are simply liquid CoQ10, meaning dry CoQ10 crystals have been dissolved, and typically, combined with oil to enhance absorption. For example, Q-Best contains liquid CoQ10 along with conjugated linoleic acid (CLA), flaxseed oil and
monoglycerides.
CoQ10 found in most supplements is in the oxidized state (ubiquinone), but once in the body it readily goes into the reduced state (ubiquinol), which is its active, anti-oxidant form. Ubiquinol predominates in the body. You can purchase supplements in which CoQ10 is already in the active ubiquinol state. Ubiquinol is sometimes referred to as CoQH-10 or CoQH2-10. Ubiquinol appears to have superior bioavailability to CoQ10. A small study in healthy volunteers comparing 200 mg of each ingredient in identical softgel capsules found that, after 4 weeks of daily treatment, each significantly raised blood levels of total CoQ10, but ubiquinol raised it 72% more than CoQ10.
Dosage
CoQ10:
The suggested daily dosage of CoQ10 varies widely and can range from 50 mg to 400 mg of CoQ10 or ubiquinol. It is best to determine your dosage based on amounts that have shown to be clinically effective (as described below) and based on the recommendations for you. Using CoQ10 to treat congestive heart failure should be considered an adjunct to, not a replacement for, other medications. A daily dose of 100 mg to 300 mg of CoQ10 is generally used. Be aware that improvement in symptoms may take more than one month. Don't suddenly stop taking CoQ10, because symptoms may worsen. Tapering off the supplement is recommended. CoQ10 in a daily dose of 300 mg may help prevent migraine headaches, but doesn't affect the severity or duration of migraines
once they begin. It can take up to three months to achieve the full migraine preventing benefits of CoQ10. For reducing muscle pain associated with statin use, a dose of 50 mg twice daily may be helpful.
For other diseases, the following daily doses have been used, although optimal dosage levels have not been determined: For reducing the risk of pre-eclampsia during pregnancy 200 mg; for hypertension 120 to 200 mg; for angina 150 mg; for reducing the likelihood of future heart problems in people who've had a first heart attack 120mg; for muscular dystrophy 100 mg; for mitochondrial encephalomyopathies 150 to 160 mg and sometimes higher; for increasing sperm motility 200 to 300 mg.
A very small Japanese study of eleven healthy elderly subjects given 100 mg per day of ubiquinol showed increases in self-assessed "vitality" and "mental health". This dose increased plasma concentrations of ubiquinol by four-fold and increased the ratio of ubiquinol to CoQ10. Interestingly, the effects were correlated with the increased ratio rather than the increased concentration.
A study in veterans with Gulf War illness found that taking 100 mg of CoQ10 (in oil from a softgel) daily for 3 to 4 months appeared to improve physical functioning and, among men, general self-rated health.
Divided dosing (taking two or three equally divided smaller doses instead of one large dose a day) is recommended when the total daily dose exceeds 100 mg. It is also recommended that you take CoQ10 with fatty meals to help increase absorption.
Safety
A study involving over 100 people with cardiomyopathy taking CoQ10 (100 mg daily, divided into three doses) for several years (some as long as 6 years) concluded that CoQ10 was safe. Doses as high as 1,200 mg per day (divided into four doses taken with meals and at bedtime) were used in a placebo-controlled study lasting 16 months which found CoQ10 to be safe and well tolerated. Because safety during pregnancy and lactation has not been established, CoQ10 should not be used during these times unless the potential clinical benefit outweighs the risks. CoQ10 is contraindicated in cases of known hypersensitivity. In a series of 5143 patients treated with 30 mg/ day of CoQ10, the following incidence of side effects was reported: Epigastric discomfort, 0.39% - Loss of appetite, 0.23% - Nausea, 0.16% - Diarrhea, 0.12%
Interactions
Cholesterol-lowering statin drugs such as lovastatin, rosuvastatin, and pravastatin inhibit the enzyme 3-hydroxy-3-methylglutaryl CoA reductase, which is required for biosynthesis of both cholesterol and CoQ10. Thus, administration of these drugs might compromise CoQ10 status by decreasing its synthesis, and statin-associated myopathy has been hypothesized to be related to a depletion of CoQ10. Although some trials demonstrated that statin therapy did reduce serum or muscle levels of CoQ whether or not this CoQ10 depletion caused the myopathy remains controversial. Given that statins are typically prescribed to lower cholesterol, with the intention being the prevention and treatment of cardiovascular disease, the concomitant use of Q10 seems well-justified.
The β-blockers propranolol and metoprolol were shown to inhibit CoQ10-dependent enzymes. The antihypertensive effect of these drugs might therefore be compromised in the long run by the development of CoQ10 deficiency. In one study, administration of 60 mg/ day of CoQ10 reduced the incidence of drug-induced malaise in patients receiving propranolol.
A number of phenothiazines and tricyclic antidepressants were also shown to inhibit CoQ10-dependent enzymes. It is therefore possible that CoQ10 deficiency might be a contributing factor to the cardiac side effects that are frequently seen with these drugs. In two clinical studies, supplementation with CoQ10 improved electrocardiographic changes in patients on psychotropic drugs.
Several case reports describing potential interactions between CoQ10 and warfarin have been reported. CoQ10 is structurally related to menaquinone (vitamin K2) and may have procoagulant effects. In each of these patients, the international normalized ratio (INR), which had been stable and therapeutic, fell below the therapeutic range within 2 weeks of beginning CoQ10 supplementation (as low as 30 mg/ day). The INR returned to the therapeutic range after CoQ10 was discontinued. It is recommended that the INR be monitored closely if these agents are to be used concomitantly. However, in a double-blind trial, administration of 100 mg/ day of CoQ10 for 4 weeks had no effect on the INR in 21 patients on long-term warfarin therapy. Thus, the sporadic case reports of an interaction between CoQ10 and warfarin might have been due to random fluctuations in INR values, rather than to CoQ10.
A dose of 100 mg or more of CoQ10 taken in the evening may cause mild insomnia in some individuals. Even if taken during the day, high-dose CoQ10 (300 mg) may also cause sleep problems, as suggested by a small study of veterans with Gulf War illness: 74% reported sleep problems before the study. This fell to 64% among those given 100 mg of CoQ10 daily but increased to 83% among those given 300 mg. If CoQ10 seems to cause insomnia, take it well before dinner time and consider reducing the dose.
Thyroid hormones can affect CoQ10 levels in the body; in hyperthyroidism (overactive thyroid) CoQ10 levels have been found
to be the lowest discovered in human diseases, while in hypothyroidism (underactive thyroid), CoQ10 levels tend to be elevated. Treatment of hyperthyroidism in children with metimazole (Tapazole) has been shown to normalize CoQ10 levels in the body. However, it is not known whether CoQ10 supplementation affects thyroid hormone levels and interactions between CoQ10 and medication for hypothyroidism, such as levothyroxine (Synthroid) have not been reported.