Accurate Education – CoQ10

Coenzyme Q10 (CoQ10)

 

CoQ10 – Neurobiology

CoQ10 has a fundamental role in cellular bioenergetics as a cofactor in the mitochondrial electron transport chain and is essential for the production of ATP. While most of the beneficial effects of CoQ10 are attributed to  energy production, the functions of CoQ10 go beyond the mitochondria. CoQ10  is a potent lipophilic antioxidant; it protects intra- and extra-cellular components from free radical damage. A potent antioxidant, CoQ10 also recycles and regenerates other antioxidants such as Vitamin E (tocopherol) and Vitamin C (ascorbate). Additionally, CoQ10 is involved in cell signaling and gene expression.

 

CoQ10 – Deficiency

 Susceptibility to CoQ10 deficiency appears to be greatest in cells that are metabolically active (such as cells in the heart, immune system, gingiva, and gastric mucosa), since these cells have the highest requirements for CoQ10. CoQ10 deficiencies may be due to genetic variations, mitochondrial diseases, aging-related oxidative stress (See Antioxidants and Oxidative Stress), and treatment with medications such as statins for treating elevated cholesterol. Many cardiovascular diseases, fibromyalgia, diabetes, cancer, and muscular and  neurodegenerative disorders have been associated with low CoQ10 levels.

 
CoQ10 is synthesized in the liver but is also provided by dietary intake from foods and/or dietary supplements. The effect of diet is of particular importance, since CoQ10 has a relatively long circulatory half-life (approx. 24-48 hours), and dietary intake may contribute up to 25% of the total amount of plasma CoQ10. While dietary contributions of CoQ10 to plasma levels are relatively small compared to liver biosynthesis, supplementation is effective in increasing plasma CoQ10 levels. However, it does appear that tissues levels of CoQ10 can reach a saturation level where additional supplementation with CoQ10 does not further increase tissue levels.
 

CoQ10 – Diet and Absorption

Diet

Dietary CoQ10 is naturally found in both forms: CoQ10 (ubiquinone) and its reduced form, H2CoQ10 (ubiquinol), with large amounts present in heart, chicken leg, herring, and trout. The daily intake from food is estimated to be 3–5 mg CoQ10 a day.

 

CoQ10 contents in foods (Total CoQ10 (μg/g wet weight):

Meats:

Beef:

Beef Sirloin (30)
Beef tenderloin (26)

Pork:

Sirloin (14)
Heart (118)
Liver (54)

Chicken:

Chest (16)
Heart (123)
liver (116)

 

Fish:
Salmon (7.6)
Eel (7.4)
Squid (3.8)

 

Vegetables:
Chinese cabbage  (2.7)
Eggplant (2.2)
Parsley (26)

 

 

Absorption of CoQ10 from the GI Tract

CoQ10 absorption is a complex process and is dependent upon active and passive transport mechanisms. Intestinal absorption is 3-times faster if CoQ10 is administrated with food. CoQ10 is absorbed slowly from the small intestine because it has a high molecular weight and is not very water soluble. Once absorbed, ubiquinone is converted to ubiquinol, both then pass into the lymphatics, and finally to the blood and tissues. CoQ10 absorption and bioavailability vary greatly depending on the form of CoQ10 ingested. CoQ10 may be slightly better absorbed in oil-based forms and gel-caps may be preferred as they contain a liquid form of Coenzyme Q10, which is also thought to be better absorbed and utilized than powdered forms.

 

CoQ10 as ubiquinone is poorly absorbed following oral ingestion necessitating use of high dosages of ubiquinone in order to obtain the desired physiological effects. The reduced form of CoQ10, ubiquinol, has been shown to have better bioavailability, with a  4.7-fold increase in plasma ubiquinol compared to a  single oral ingestion of ubiquinone at a dosage of 300 mg, and a 10-fold increase following 28 days of treatment with ubiquinol vs. ubiquinone. However, the efficiency of absorption decreases as the dose increases. 

 

CoQ10  –  Drug Interactions

Drug- CoQ10 Interactions That Lower CoQ10 Levels

(or Drugs that Suggest Potential Benefit of Supplementation with CoQ10

 

Statins

Cholesterol-lowering drugs such as atorvastatin (Lipitor), lovastatin (Mevacor), and pravastatin (Prevachol) inhibit the enzyme HMG-CoA reductase, an enzyme required for synthesis of cholesterol as well as CoQ10, resulting in decreased blood levels of CoQ10.

 

Beta blockers

Beta blockers such as propranolol (Inderal) and metoprolol (Toprol), have been shown to inhibit CoQ10-dependent enzymes.

 

Others

Phenothiazines (promethazine/phenergan & haldol) and tricyclic antidepressants (Elavil/amitriptyline & doxepin) have also been shown to inhibit CoQ10-dependent enzymes.

 

Drug- CoQ10 Interactions Where CoQ10 Affects Other Drugs

Insulin

CoQ10 may affect blood sugar levels. Caution is advised in people with diabetes or low blood sugar, and in those taking drugs, herbs, or supplements that affect blood sugar. CoQ10 may improve beta-cell function in the pancreas and enhance insulin sensitivity, which may reduce insulin requirements in diabetic patients.

 

 

Side Effects

CoQ10 treatment is safe, even at the highest doses cited in the literature. Most clinical trials have not reported significant adverse effects that necessitated stopping therapy and CoQ10 is likely safe when up to 3,000 milligrams is taken by mouth daily for up to eight months in healthy people.  However, CoQ10 should be used cautiously in high doses over a long period of time. CoQ10 should also be used cautiously in  people with liver problems. Doses of greater than 300 milligrams daily may affect levels of liver enzymes.

 

Gastrointestinal System

Side effects involve the gastrointestinal system and may include nausea, diarrhea, appetite suppression, heartburn and epigastric discomfort. In large studies the incidence of gastrointestinal side-effects is less than 1%.

 

Bleeding

CoQ10 may increase the risk of bleeding. Caution is advised in people with bleeding disorders or taking drugs that may increase the risk of bleeding. Dosing adjustments may be necessary.Use cautiously in people who are taking coumadin (warfarin.) because CoQ10 may reduce the effectiveness of coumadin. Also, CoQ10’s antiplatelet effect may increase the risk of bleeding.

 

CoQ10 – Measurement of CoQ10 Levels

 
Measuring levels of CoQ10 may identify individuals most likely to benefit from supplementation therapy. Also, during supplementation it may be advised to monitor plasma CoQ10 levels to ensure dosing effectiveness,  especially because the variable bioavailability between commercial formulations and known inter-individual variation in CoQ10 absorption.
 
CoQ10 is lipophilic and transported in lipoprotein particles in the circulation. It is not surprising therefore that plasma CoQ10 correlates positively with plasma total cholesterol and LDL-cholesterol. It has been proposed that the ratio of CoQ10 to LDL levels be evaluated for a more accurate assessment of blood levels.

 
“Normal” CoQ10 levels range from 0.40 to 1.91 μmol/l (0.34–1.65μg/ml)

Dosing
In most cases, supplementation with CoQ10, preferably the ubiquinol form, the daily dose advised is 100-200 mg 2-3 times a day. CoQ10 dosing appears to be safe and well tolerated at doses up to 1,200 mg/day  for adults. Side effects have been reported to be no more common at doses up to 1,200 mg/day than at 60 mg/day. Steady-state plasma concentrations at these dosage levels generally range from 5 to 10 μg/ml.

 

Blood Levels

The plasma threshold for the uptake of CoQ10 appears to be different for different tissues. Higher than ‘normal’ levels of plasma CoQ10 appear necessary to facilitate tissue uptake and allow transfer of CoQ10 across the blood brain barrier. In one study with congestive heart failure patients, it was reported that those with a plasma CoQ10 value of 2.4 lg/mL (2.780 lmol/L) showed the highest benefit. In another study with CHF patients, it was reported that a blood CoQ10 concentration of at least 3.5 lg/mL (4.054 lmol/L) appeared to be necessary before any therapeutic benefit from CoQ10 supplementation could be expected. The plasma threshold appears to be much higher for neurodegenerative diseases such as Huntington’s and Parkinson’s, based upon the CoQ10 dosages required to achieve clinical response.

 

Plasma CoQ10 levels as high as 10.7 μM have been reached following supplementation with solubilised formulations of ubiquinol. High levels have been tested without adverse effects and may be safe, but the data for intakes above 1200 mg/day are not sufficient for a confident conclusion of safety. Plasma CoQ10 concentrations plateau at a dose of 2400 mg/day.

 

Plasma CoQ10 status is highly dependent upon the concentration of lipoproteins which are the major carriers of CoQ10 in the circulation, with approximately 58% of total plasma CoQ10 being associated with low-density lipoprotein or LDL fraction. Because of its dependence upon both dietary intake and lipoprotein concentration, plasma CoQ10 levels may not truly reflect tissue levels. It has been suggested that plasma CoQ10 levels should be expressed as a ratio to either total plasma cholesterol or LDL cholesterol in order to be of diagnostic value.

 

CoQ10 Formulations

CoQ10 in its pure form is a crystalline powder that is insoluble in water and has limited solubility in lipids, so it is therefore poorly absorbed. CoQ10 products currently available on the market include powder-based compressed tablets, chewable tablets, powder-filled hard-shell capsules and softgels containing an oil suspension. The  presence of fat may promote better absorption of CoQ10. In addition, several solubilized formulations of CoQ10 in softgel and liquid forms have become available in recent years. While there are many dosage forms available, the major issue concerning their effectiveness is based on how well they are absorbed.
 
Among both solubilized and non-solubilized formulations of CoQ10, ubiquinol is superior to ubiquinone and solubilized formulations are superior to non-solubilized formulations.

 

CoQ10 as Ubiquinol

While the efficiency of absorption decreases as the dose increases, higher doses provide substantially higher blood levels, especially with ubiquinol which is better absorbed than ubiquinone. At a daily dose of 300 mg ubiquinol oil suspension for 4 weeks, plasma ubiquinol concentration reach high levels of 8.413 lmol/L, an 11- fold increase over baseline, remarkably higher compared with results obtained with powder-based CoQ10 formulations in the form of ubiquinone.

 

The highest increase in plasma CoQ10 concentration is obtained using solubilized CoQ10 as ubiquinol at a doses of 300-600 mg/day, and these values are higher than those obtained with much larger doses of CoQ10 (up to 3000 mg) as ubiquinone. When the daily dosage is administered in two divided doses, the response to both ubiquinone and ubiquinol is even higher, reflecting the fact that absorption of CoQ10 is at least in part based on transporters which may be overwhelmed with single daily dosing.

 

Incidentally, high doses of Vitamin E, if taken along with CoQ10, may interfere with CoQ10 absorption and thus result in lower plasma CoQ10 concentrations.

 

CoQ10 as Ubiquinone

With ubiquinone dosing over a range of 30 mg to 3000 mg/day,  plasma concentrations tend to plateau at around 2400 mg with no further increase at 3000 mg. Plasma concentrations are markedly higher for the solubilized formulations of ubiquinone as compared with powder-based non-solubilized formulations but not as high as with ubiquinol.

 

CoQ10 – Addiction

CoQ10 – Arthritis (Osteoarthritis)

CoQ10 – Cancer

CoQ10 – Cardiovascular Disease

Oxidative stress plays a central role in the development of cardiovascular diseases including coronary artery disease (CAD), congestive heart failure (CHF) and high blood pressure (hypertension).
 

CoQ10 & Coronary Artery Disease

Oxidative stress contributes significantly to the development of coronary artery disease (CAD). The plasma levels of CoQ10 and certain other antioxidants tend to be lower in CAD and higher levels of plasma CoQ10 are associated with a reduced risk of CAD. CoQ10 supplements at a dose of 150 mg/day or higher have been shown to decrease oxidative stress and increase antioxidant enzyme activity including superoxide dismutase (SOD) in patients with CAD. Research supports the potential cardioprotective benefit  of supplementing with CoQ10. It has been estimated that a plasma CoQ10 concentration of about 0.70 μmol/L) is an optimal cut-off point to predict the mortality of patients with chronic heart failure.

 

CoQ10 inhibits the oxidation of protein, DNA, cell membrane lipids and also the oxidative breakdown (peroxidation) of lipoprotein lipids, especially low-density lipoproteins (LDLs), present in the circulation. This reduction of LDL peroxidation reduces the development of atherosclerosis (hardening of the arteries) that leads to increassed risk of heart attacks and strokes. Dietary supplementation with CoQ10  has a direct anti-atherogenic effect of minimizing atherosclerosis in the aorta and it appears to reduce the risk of fatal heart attacks.

 

CoQ10 & Congestive Heart Failure (CHF)

 
Heart failure is characterized by impaired cardiac muscle contraction (myocardial contractility) due to energy depletion in the mitochondria that has been associated with low CoQ10 levels. Supplementation with CoQ10 can result in improving the quality of life of cardiac patients by improving myocardial contractility. Patients with moderate to severe CHF often have limited clinical improvement and fail to achieve adequate plasma CoQ10 levels (>2.5 mcg/ml) on supplemental CoQ10 (ubiquinone) at dosages up to 900 mg/day.  It is thought that the intestinal edema (swelling) in these patients may impair ubiquinone absorption. In one study, when these patients were changed to supplementing with ubiquinol (450-900 mg/day), follow-up plasma CoQ10 levels, clinical status, and cardiac functions all improved.

 

CoQ10 & High Blood Pressure
There is evidence that CoQ10 may lower blood pressure and some researchers believe CoQ10 supplementation may reduce the need to take multiple antihypertensive drugs. Mitochondria produce reactive oxygen species that may contribute to vascular dysfunction and the regulation of blood pressure and vascular tone. CoQ10 as well as alpha-lipoic acid and acetyl-L-carnitine reduce oxidative stress and improve mitochondrial function.

 

A recent meta-analysis of clinical trials investigating the use of CoQ10 for high blood pressure noted blood pressure reduction without significant side effects in all 12 trials, regardless of whether CoQ10 was given alone or as an adjunct to standard antihypertensive medication. While further studies are needed to confirm the clinical usefulness of CoQ10, alpha-lipoic acid and acetyl-L-carnitine as antihypertensive therapy, in some cases it would be reasonable to recommend these agents as an adjunct to conventional antihypertensive therapy.

 

CoQ10 – Central Sensitivity,  Oxidative Stress & Pain

See publications below

Dental

Periodontal Disease

 

CoQ10 – Depression

There is now good evidence that major depression is accompanied by oxidative stress and systemic inflammation, both of which contribute to symptoms of depression. CoQ10 has neuroprotective properties, protecting neurons and brain cells against central neurotoxic damages from oxidative stress. Deficiency of plasma CoQ10, a strong antioxidant that resists mitochondrial damage by oxidative stress, may comtribute to depression. Moreover,  plasma CoQ10 levels are significantly lower in depressed patients than in normal controls. In one study, more than half of the depressed patients had plasma CoQ10 values that were lower than the lowest plasma CoQ10 value detected in patients without depression. Furthermore, up to 15% of depressed patients are resistant to treatment for depression and evidence indicates that oxidative stress and low plasma CoQ10 levels  are involved in treatment resistant depression (TRD).
 
Research has also demonstrated increased levels of C-reactive protein (CRP, a biomarker for  inflammation) and pro-inflammatory agents (cytokines, e.g. interleukins, interferon-γ (IFNγ) and tumor necrosis factor-α (TNFα), in patients with depression. Inflammatory responses are accompanied by an induction of oxidative stress pathways. Likewise, depression is accompanied by evidence of oxidative stress, such as increased levels of polyunsaturated fatty acid peroxidation, indicating oxidative damage by free radicals. Furthermore, depression is associated with nerve degeneration (neurodegeneration) and reduced nerve regeneration in the brain, both factors that are caused by neuroinflammatory processes.


Additional research indicating that depression is accompanied by a significantly decreased antioxidant status has demonstrated lower antioxidant levels of zinc, vitamins E and C, and glutathione peroxidase in patients with depression. It is reasonably safe to propose that low CoQ10 levels would contribute to depression and that supplementation with CoQ10 and other mitochondrial agents, such as lipoic acid and acetyl-L-carnitine may offer clinical benefit (See Lipoic Acid and Acetyl-L-Carnitine).
 

Depression and Cardiovascular Disorders

A low CoQ10 syndrome in major depression also offers another explanation for the high comorbidity between cardiovascular disorders and depression. It is now well established that major depression is a significant risk factor to coronary artery disease (CAD) and that the comorbidity between depression and CAD results in an increased cardiovascular mortality.

 

CoQ10 – Diabetes

Many studies suggest a central role for oxidative stress in the development of this multifaceted metabolic disorder and has resulted in the use of antioxidants including CoQ10 as complementary therapeutic agents. Serum CoQ10 levels are often decreased in type 2 diabetic patients and may be associated with diabetic polyneuropathy and subclinical diabetic cardiomyopathy, reversible by CoQ10 supplementation.
 

CoQ10 – Dry Mouth

A study published in 2011 in which sixty-six patients were given either ubiquinol or ubiquinone orally at a dosage of 100 mg/day or a placebo for 1 month revealed that both forms significantly improved dry mouth symptoms.

CoQ10 – Endometriosis

 

CoQ10 – Chronic Fatigue Syndrome (CFS)

Coenzyme Q10 Plus NADH Supplementation

A recent 8-week, randomized, double-blind placebo-controlled study evaluated the benefits of oral CoQ10 (200 mg/day) plus NADH (20 mg/day) supplementation with CFS and found significant improvement of fatigue and a number of biochemical parameters improved. According to this study, the CoQ10 plus NADH combination induced a significant reduction of fatigue, decrease in oxidative damage, improvement of mitochondrial function, and enhancement of energy, suggesting a potential role of these agents in managing CFS.

 

Coenzyme Q10, Statins and CFS

Since statins significantly decrease plasma CoQ10, CFS should be regarded as a relative contraindication for treatment with statins without CoQ10 supplementation.

 

CoQ10 – Fibromyalgia (FM)

Recent studies demonstrate that mitochondrial dysfunction and oxidative stress are implicated in the severity of clinical symptoms in FM. Moreover, in addition to the presence of oxidative stress, FM is also characterized by  inflammatory responses including pro-inflammatory cytokine production. In association with these findings, reduced levels of CoQ10, increased levels of mitochondrial free radicals (superoxide), and increased levels of lipid peroxidation in blood mononuclear cells from FM patients. These findings argue strongly for the potential benefit of CoQ10 supplementation as a means of treating FM symptoms.
 
Multiple studies have demonstrated reduced symptoms of FM with CoQ10 suppementation.  CoQ10 supplementation (300 mg/day) reduces pain, tenderness, fatigue, morning tiredness and improves non-restful sleep in FM. Oxidative stress has been found to correlate with headache symptoms in fibromyalgia and CoQ10 treatment can be effective for treating headache in FM. Studies have demonstrated improvement of FM symptoms within 3 months and persisting with continued treatment for 9 months or longer.

CoQ10 – Headaches (Migraine)

It is believed that oxidative stress and lipid peroxidation (LPO) play a role in the development of migraine by regulating cerebral blood flow and energy metabolism which may trigger migraine attacks. Mitochondria are believed to be involved in the cause of migraines, although a direct link has not been identified. In addition, the inflammatory component of migraines may produce oxygen free radicals, consuming CoQ10 and inducing CoQ10 deficiency. Oxidative stress has been found to correlate with headache symptoms in fibromyalgia (FM) and CoQ10 treatment showed a remarkable improvement in headache in FM.
 
Coenzyme Q10 is effective for both classic migraine (with aura) and common migraine (without aura) with few significant side-effects. In one study, 61.3% of the patients in the study achieved at least a 50% reduction in frequency of migraine attacks by the end of the four-month trial, at a dose of CoQ10 150 mg per day. There were no side-effects noted. As with most migraine preventives, it takes five to 12 weeks to achieve more than a 50% reduction.
 
Another small study of 20 adult patients with migraine without aura were followed for 60 days of dosing C0Q-10 at 200 mg/day showed significant improvement in frequency and severity of headaches with no significant side effects.
 

Pediatric and Adolescent Migraine
A study evaluating 1550 migraine patients (3 to 22 years old).identified 32.9% having CoQ10 levels below the reference range. Patients with low CoQ10 were given 1 to 3 mg/kg per day of CoQ10 in liquid gel capsule formulation. At follow-up in 3 months, total CoQ10 levels improved and both headache frequency and headache disability improved.

 

CoQ10 – Interstitial Cystitis
 

CoQ10 – Obesity

 

CoQ10 – Pain

Treatment of CoQ10 decreased pain-related hypersensitivity.
 

CoQ10 – Diabetic Peripheral Neuropathy (DPN)

Diabetic peripheral neuropathy (DPN) is a serious complication of both type 1 and type 2 diabetes, affecting up to 50% of diabetic patients. It can precede findings of elevated blood sugar in some cases. Many patients initially experience tingling or pain in their toes, feet or fingers. This pain is often accompanied by hyperalgesia, a heightened sense of pain in response to mechanical or thermal stimulation or allodynia, a painful sensation in response to stimulation such as light touch which would not normally be perceived as painful. Over time, pain often subsides and is replaced by diminished or loss of sensation.

 

In DPN, nerves have increased lipid peroxidation (see above) along with reduced levels of CoQ10. Supplementation with CoQ10 has been shown to reduce lipid peroxidation and increase levels of CoQ10 along with an improvement in the pain. A twelve weeks study of treatment with ubiquinone 400mg/day improved clinical outcome and nerve conduction in 24 patients with diabetic neuropathy without significant adverse events.

 

Despite multiple popular articles promoting the use of CoQ10 in DPN. there is a laxk of definitive research to confirm CoQ10 benefits for DPN. Nevertheless, it is considered a safe treatment option that may warrant clinical trials to establish effectiveness.

 

CoQ10 – Statins (Medications used to reduce cholesteral such as Lipitor)