Accurate Education – CoQ10

Coenzyme Q10 (CoQ10)

Coenzyme Q10 (CoQ10) is an essential compound found naturally in virtually every cell in the human body. CoQ10 is essential for energy production in cell mitochondria, where energy is produced from oxygen and other essential nutrients. CoQ10 also functions as an antioxidant and has been shown to modulate gene expression. Dietary supplementation to raise CoQ10 levels has been shown to have multiple beneficial effects in many different conditions. Diet supplements of CoQ10 come in two forms, ubiquinone and ubiquinol.

 

See:

Accurate Supplements

 

See Also:

Antioxidants and Oxidative Stress

Fibromyalgia – CAM Treatment

Headaches – CAM Treatment

Mitochondrial Dysfunction

 

Purchasing Supplements

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“I realized that if my thoughts immediately affect my body, I should be careful about what I think. Now if I get angry, I ask myself why I feel that way. If I can find the source of my anger, I can turn that negative energy into something positive.”

– Yoko Ono

Coenzyme Q10 (CoQ10)

Overview

Coenzyme Q10 (CoQ10), is an essential compound found naturally in virtually every cell in the human body. Adequate amounts of CoQ10 are necessary for cellular health; it is present in cell membranes, blood, and in both high- and low-density lipoproteins. Because of its ubiquitous presence in nature and its quinone structure, CoQ10 is known as ubiquinone.  CoQ10 functions like a vitamin, but it is not considered a vitamin because unlike vitamins it is synthesized in the liver. Coenzyme Q10 (CoQ10) is an essential part of the energy producing mechanism inside every cell in which food is converted to energy for muscle contraction and other vital cellular functions. CoQ10 may help with heart-related conditions such as  coronary artery disease, high blood pressure and preventing blood clot formation and may also benefit certain medical conditions including fibromyalgia and chronic fatigue syndrome.

 

CoQ10 has an essential role in mitochondrial function as part of the cellular system that produces energy from nutrients and oxygen. CoQ10 also has potent antioxidant benefits. These two functions are the main arguments for clinical use of CoQ10 as a supplement. Recent studies also indicate that CoQ10 affects the expression of genes involved in cellular communication and metabolism, suggesting that some of the effects of CoQ10 supplementation may also be due to this property.

(See Antioxidants and Oxidative Stress)

 

Dietary supplementation to increase CoQ10 levels has been shown to provide multiple beneficial effects. CoQ10 treatment does not cause serious side effects and new formulations have been developed that increase CoQ10 absorption and tissue distribution.  As such, oral supplementation with CoQ10 is a frequent antioxidant strategy in many diseases and may provide a significant symptomatic benefit. 

 

One concern sometimes voiced is whether or not supplementing with CoQ10 may negatively affect the body’s own production of CoQ10. Fortunately, several studies have shown that this is not the case. Even at very high levels of ubiquinol supplementation greater than a 1000 milligrams/day  – natural production by the liver remains unaffected. The safety profile for ubiquinol is excellent: even at very large doses, no adverse effects or drug interactions have ever been found or reported.

 

CoQ10 – Ubiquinone vs Ubiquinol

CoQ10 can be found in two forms: its oxidized form CoQ10 (ubiquinone) and its reduced form, H2CoQ10 (ubiquinol). The pharmacokinetic profile of ubiquinone is identical to that of ubiquinol except that the rate of gastrointestinal (GI) absorption of ubiquinol is much greater. Once ingested, ubiquinone is slowly absorbed in the GI tract due to its hydrophobicity and relatively large molecular weight. Ubiquinone is converted to ubiquinol in the gut wall prior to its lymphatic transport into the blood circulation. Once absorbed, the circulating form of CoQ10 in the blood is about 95% ubiquinol, regardless of whether one supplements with ubiquinone or ubiquinol.  The elimination half-life of ubiquinol is about 24-48 hours. 

 

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 deficiency may result from:

  1. Impaired synthesis due to nutritional deficiencies
  2. Genetic or acquired defect in synthesis or utilization
  3. Increased tissue needs associated with illness or disease processes
  4. Reduced production of CoQ10 associated with advancing age

 

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.

 

Other possible drug interactions with CoQ10 include: ACE Inhibitors (such as enalapril), blood pressure medications, calcium-channel blockers (such as diltiazem), fibric acid derivatives, doxorubicin, nitrate and warfarin (coumadin).

 

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

The periodontal diseases, gingivitis and periodontitis, are oral inflammatory conditions of infectious nature. Gingivitis is a reversible inflammatory reaction that leads to plaque accumulation, whereas periodontitis is a destructive, non-reversible condition resulting in loss of tooth connective tissue attachment to bone which ultimately leads to loss of the involved teeth.

 

Periodontitis is an inflammatory disease process that is the direct result of accumulation of subgingival plaque . The bacteria associated with this plaque cause tissue destruction directly by releasing toxic products and indirectly by activating local defense systems, i.e. inflammation. The toxic molecules believed to trigger the inflammatory response include free radicals and reactive oxygen species (ROS). Periodontal bacteria can induce ROS overproduction which causes collagen and periodontal cell breakdown. When ROS are scavenged by antioxidants, it can reduce collagen degradation. There is evidence that CoQ10, as an antioxidant, may reduce this damage in diseased gingiva and effectively suppress advanced periodontal inflammation.

 

CoQ10 is used routinely, both topically and systemically, by many dentists and periodontists as an adjunctive treatment for periodontitis, alone or in combination with other synergistic antioxidants including vitamins C and E. Because gingivitis leads to periodontits, CoQ10 supplementation along with scaling and root planing can prevent periodontitis by reducing gingival inflammation. The use of topical CoQ10, such as Perio-Q (CoQ) gel, may also have a potential additive effect.

 

 

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)

Chronic fatigue syndrome (CFS) is a serious and complex chronic illness with no known cause, diagnostic test, or universally effective treatment. It is characterized by prolonged and relapsing fatigue that results in significant disability, often for years.  The cause of CFS is unclear; however, inflammation, oxidative stress, mitochondrial dysfunction and CoQ10 deficiency have been well documented in CFS and likely contribute to the fatigue. Plasma CoQ10 levels are significantly reduced in patients with CFS and levels correlate with severity of some of the symptoms of CFS including concentration and memory disturbances which appear to correlate with very low CoQ10 levels (<390 mcg/L).

 

Coenzyme Q10 Plus NADH Supplementation

NADH is a mitochondrial coenzyme that stimulates energy production by replenishing depleted cellular stores of ATP. The NAD + / NADH ratio plays an major role in regulating intracellular oxidative status and therefore reflects the function of the metabolic state. Given the major contributions of NADH and CoQ10 in maintaining normal cellular energy production, especially during increased oxidative stress and conditions of inflammation, supplementation with both agents represents a potentially effective means of treating fatigue.

 

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)

Statins are medications used for the treatment of elevated cholesterol to reduce risk of coronary artery disease and to prevent stroke. Their mechanism of action is the inhibition of cholesterol synthesis by inhibiting the co-enzyme HMG-CoA) reductase. However, because both cholesterol and CoQ10 synthesis depend on HMG-CoA reductase, statins are also likely to reduce levels of CoQ10.

 

An important factor contributing to statin related myopathy may be genetic susceptibility to muscle disorders. It has been reported that a 2.33–2.58 fold increase in the relative risk of statin intolerance is associated with polymorphisms (variants) in the CoQ2 gene. Also, recent research has identified a genetic variant associated with a liver enzyme, the CYP2D6*4 polymorphism, which is associated with a reduction of statin metabolism and has been linked to statin-induced muscle effects.

 

Side effects associated with statins commonly include muscle complaints, including myopathy (impaired muscle function), myalgia (muscle pain) and muscle injury which are thought to be due to a deficiency of CoQ10 in muscle mitochondria. Research confirms that statins reduce CoQ10 levels in blood and that supplementation with CoQ10 increases these levels. However, research regarding the benefit of statin therapy on CoQ10 levels in muscle has been conflicting. Some studies show that CoQ10 may counteract the muscle aches associated with taking statins and other studies indicate CoQ10 improves fatigue associated with physical exercise. 

CoQ10 – Supplement Formulations

 

CoQ10 – Bioavailability

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 following single oral ingestion of ubiquinone at a dosage of 300 mg, and a 10-fold increase following 28 days of treatment.  Since ubiquinone is converted to ubiquinol in the body once ingested, supplementation with ubiquinol provides the same benefits as with ubiquinone but requires smaller doses.

 

CoQ10 Supplements
There are many different brands of CoQ10 supplement available, and their formulations can differ widely in respect to whether they contain reduced (ubiquinol) or oxidised CoQ10 (ubiquinone), whether they are dry powder capsules or CoQ10 dispersed in oil, and whether they contain surfactants and emulsifiers, such as lecithin and polysorbate 80 to improve absorption. There is a significant difference in bioavailability of the various brands and formulations of CoQ10 supplement.

 

Commercial coenzyme Q10 (CoQ10, ubiquinone) formulations often have poor intestinal absorption. The relative bioavailability of CoQ10 has been shown in National Institutes of Health-funded clinical trials to be increased by its delivery system. Solubilized formulations of CoQ10 (both ubiquinone and ubiquinol) have superior bioavailability.

 

CoQ10, bioavailability is known to be influenced by modality of administration, with higher plasma levels reached by administration of the same amount divided in multiple doses. Product types with soft gels containing oils or triglyceride mediums show better bioavailability in comparison with the crystalline, powdered form of Coq10.

 

Higher plasma CoQ10 concentrations are necessary to facilitate uptake by peripheral tissues and also the brain. Most bioavailability studies have evaluated plasma CoQ10 levels rather than mitochondrial levels, but new analogues have been developed designed to to enhance mitochondrial uptake, including mitoquinone-Q (Mito-Q) in which ubiquinol is attached to another molecule that facilitates its absorption into the mitochondria. Similar agents using Vitamin E, lipoic acid and other antioxidants are being invsatigated. Unfortunately there are no recent definitive, conclusive studies that compare the bioequivalence of different brands head-to-head.

 

Most importantly, there is also a significant difference in absorption of CoQ10 from supplements between individuals, ranging up to 29% difference. These variations between product and individual absorptions highlight the need to monitor plasma CoQ10 concentrations during supplementation.

 

At this date it appears that the best options for supplementing with CoQ10 are:

(1) Ubiquinol rather than ubiquinone

(2) Solubilized or colloidal formulas

(3), Take the supplement with meals and divide daily doses into 2-3 doses/day

(4)  Monitor blood levels

(5) Consider mitochondrial formulations but it is not practical to monitor mitochondrial levels to confirm benefit.

 

 Note: Brands labeled only as Coq10 are ubiquinone and are usually oil suspensions, powders or soft gels and are not solubilized

 

CoQ10 – Quality Control
Because CoQ10 has a rather complicated chemical structure and possesses several physical properties, such as low melting point, hydrophobic nature, and light sensitivity, it does not favor large-scale commercial production and highly sophisticated techniques need to be employed at all production stages to obtain a high quality product. For this reason, it would make sense to avoid off-brand labels when purchasing CoQ10 supplements and to be particularly wary of deals that appear disproportionately inexpensive.

 

What appears to be the most popular and the brand with the best reputation for ubiquinol quality is the Kaneka brand.

 

 

Reference Publications

CoQ10 –  Overview

  1. CoQ10 – Brief Summary
  2. Coenzyme Q10 Therapy
  3. Impact of Oral Ubiquinol on Blood Oxidative Stress and Exercise Performance
  4. Therapeutic use of coenzyme Q10 and coenzyme Q10-related compounds and formulations. – PubMed – NCBI
  5. Primary and secondary coenzyme Q10 deficiency: the role of therapeutic supplementation. – PubMed – NCBI
  6. Novel Therapeutic Targets in Depression and Anxiety – Antioxidants as a Candidate Treatment

 

CoQ10 – Ubiquinone vs Ubiquinol

  1. What’s the Difference Between Ubiquinone and Ubiquinol?

 

CoQ10 – Dosing and Safety

  1. Risk assessment for coenzyme Q10 (Ubiquinone). – PubMed – NCBI
  2. Safety assessment of coenzyme Q10 (Kaneka Q10) in healthy subjects: a double-blind, randomized, placebo-controlled trial. – PubMed – NCBI 
  3. Study on safety and bioavailability of ubiquinol (Kaneka QH) after single and 4-week multiple oral administration to healthy volunteers – 2007

 

CoQ10 – Measurement of CoQ10 Levels

  1. Coenzyme Q10 – Is There a Clinical Role and a Case for Measurement?
  2. Biochemical Assessment of Coenzyme Q10 Deficiency
  3. Biochemical Diagnosis of Coenzyme Q10 Deficiency – 2014
  4. Plasma coenzyme Q10 response to oral ingestion of coenzyme Q10 formulations 2007

 

CoQ10 – Cardiovascular

  1. Co-enzyme Q10 supplementation for the primary prevention of cardiovascular disease. – PubMed – NCBI
  2. Coenzyme Q10 supplementation reduces oxidative stress and increases antioxidant enzyme activity in patients with coronary artery disease. – PubMed – NCBI
  3. Effects of coenzyme Q10 supplementation on inflammatory markers (high-sensitivity C-reactive protein, interleukin-6, and homocysteine) in patients … – PubMed – NCBI
  4. Supplemental ubiquinol in patients with advanced congestive heart failure. – PubMed – NCBI
  5. The Relationship between Coenzyme Q10, Oxidative Stress, and Antioxidant Enzymes Activities and Coronary Artery Disease
  6. Reduced Cardiovascular Mortality 10 Years after Supplementation with Selenium and Coenzyme Q10 for Four Years – 2015
  7. Bioenergetic and antioxidant properties of coenzyme Q10- recent developments. 2007 – PubMed – NCBI
  8. CoQ10 and L-carnitine for Statin Myalgia?
  9. Effect of Combined Treatment with Alpha Lipoic Acid and Acetyl- L-Carnitine on Vascular Function and Blood Pressure in Coronary Artery Disease Patients – 2009
  10. Lipid lowering nutraceuticals in clinical practice – position paper from an International Lipid Expert Panel – 2017
  11. Effects of a Combined Nutraceutical on Lipid Pattern, Glucose Metabolism and Inflammatory Parameters in Moderately Hypercholesterolemic Subjects – 2017

 

CoQ10 – Central Sensitivity,  Oxidative Stress & Pain

  1. A newly identified role for superoxide in inflammatory pain. 2004
  2. Roles of Reactive Oxygen and Nitrogen Species in Pain – 2011
  3. Microglial Inhibitory Mechanism of Coenzyme Q10 Against Aβ (1-42) Induced Cognitive Dysfunctions – Possible Behavioral, Biochemical, Cellular, and Histopathological Alterations – 2016
  4. Spinal glial activation and oxidative stress are alleviated by treatment with curcumin or coenzyme Q in sickle mice

CoQ10 – Depression

  1. Lower plasma Coenzyme Q10 in depression – a marker for treatment resistance and chronic fatigue in depression and a risk factor to cardiovascular disorder in that illness
  2. Novel Therapeutic Targets in Depression and Anxiety – Antioxidants as a Candidate Treatment

 

CoQ10 – Dental: Periodontal Disease

  1. Role of coenzyme Q10 as an antioxidant and bioenergizer in periodontal diseases 2010
  2. Clinical evaluation of topical application of perio-Q gel (Coenzyme Q10) in chronic periodontitis patients – 2012
  3. A comparative evaluation of topical and intrasulcular application of coenzyme Q10 (Perio Q™) gel in chronic periodontitis patients: A clinical study- 2014
  4. Effectiveness of CoQ10 Oral Supplements as an Adjunct to Scaling and Root Planing in Improving Periodontal Health -2015

  

CoQ10 – Diabetes

  1. Supplementation of Coenzyme Q10 among Patients with Type 2 Diabetes Mellitus – 2015
  2. The effects of coenzyme Q10 supplementation on cardiometabolic markers in overweight type 2 diabetic patients with stable myocardial infarction – 2016

CoQ10 – Dry Mouth

  1. Effects of coenzyme Q10 on salivary secretion. 2011 – PubMed – NCBI

 

CoQ10 – Fatigue & Chronic Fatigue Syndrome

  1. Coenzyme Q10 deficiency in myalgic encephalomyelitis:chronic fatigue syndrome (ME:CFS) is related to fatigue, autonomic and neurocognitive symptoms… – PubMed – NCBI
  2. Does Oral Coenzyme Q10 Plus NADH Supplementation Improve Fatigue and Biochemical Parameters in Chronic Fatigue Syndrome?
  3. The role of mitochondrial dysfunctions due to oxidative and nitrosative stress in the chronic pain or chronic fatigue syndromes and fibromyalgia patients – 2013

 

CoQ10 – Fatty Liver Disease

  1. The Emerging Role of Disturbed CoQ Metabolism in Nonalcoholic Fatty Liver Disease Development and Progression – 2015

 

CoQ10 – Fibromyalgia

  1. Benefits of Coenzyme Q10 | Fibromyalgia Natural Relief
  2. Can coenzyme q10 improve clinical and molecular parameters in fibro… – PubMed – 2013
  3. Coenzyme Q10 Regulates Serotonin Levels and Depressive Symptoms in Fibromyalgia Patients – 2013
  4. Effect of coenzyme Q10 evaluated by 1990 and 2010 ACR Diagnostic Criteria for Fibromyalgia and SCL-90-R – 2013
  5. Fibromyalgia: unknown pathogenesis and a “chicken or the egg” causa… – PubMed – 2012
  6. NLRP3 inflammasome is activated in fibromyalgia: the effect of coen… – PubMed – 2014
  7. Oral coenzyme Q10 supplementation improves clinical symptoms and re… – PubMed – 2012
  8. Oxidative stress and mitochondrial dysfunction in fibromyalgia. – PubMed – 2010
  9. Is Inflammation a Mitochondrial Dysfunction-Dependent Event in Fibromyalgia?
  10. Mitochondrial myopathy presenting as fibromyalgia -a case report – 2012
  11. Oxidative Stress Correlates with Headache Symptoms in Fibromyalgia – Coenzyme Q10 Effect on Clinical Improvement
  12. Fibromyalgia Syndrome in Need of Effective Treatments – 2015
  13. Role for a water-soluble form of CoQ10 in female subjects affected by fibromyalgia. A preliminary study. – PubMed – NCBI

 

CoQ10 – Headaches (Migraine)

  1. A randomized, double-blinded, placebo-controlled, crossover, add-on study of CoEnzyme Q10 in the prevention of pediatric and adolescent migraine. – PubMed – NCBI
  2. Coenzyme Q10 deficiency and response to supplementation in pediatric and adolescent migraine. – PubMed – NCBI
  3. Improvement of migraine symptoms with a proprietary supplement containing riboflavin, magnesium and Q10 – Dolovent – 2015
  4. Open label trial of coenzyme Q10 as a migraine preventive. – PubMed – NCBI
  5. Oxidative Stress Correlates with Headache Symptoms in Fibromyalgia – Coenzyme Q10 Effect on Clinical Improvement
  6. Coenzyme Q-10 and migraine – a lovable relationship. The experience of a tertiary headache center – 2015
  7. Efficacy of coenzyme Q10 in migraine prophylaxis – a randomized controlled trial. – 2005

 

CoQ10 – High Blood Pressure

  1. Blood pressure lowering efficacy of coenzyme Q10 for primary hypertension (Review)
  2. Effect of Combined Treatment with Alpha Lipoic Acid and Acetyl- L-Carnitine on Vascular Function and Blood Pressure in Coronary Artery Disease Patients – 2009

 

CoQ10 – Inflammation

  1. Can coenzyme Q10 supplementation effectively reduce human tumour necrosis factor-α and interleukin-6 levels in chronic diseases? – 2017
  2. Effects of Coenzyme Q10 on Markers of Inflammation – A Systematic Review and Meta- Analysis – 2017

CoQ10 – Mitochondria

  1. Effect of Coenzyme Q10 supplementation on mitochondrial electron transport chain activity and mitochondrial oxidative stress in Coenzyme Q10 defici… – PubMed – NCBI
  2. Mitochondrial myopathy presenting as fibromyalgia -a case report – 2012
  3. The Mitochondrial Antioxidants MitoE2 and MitoQ10 Increase Mitochondrial Ca2+ Load upon Cell Stimulation by Inhibiting Ca2+ Efflux from the Organelle – 2008
  4. Mitochondria-targeted agents – Future perspectives of mitochondrial pharmaceutics in cardiovascular diseases – 2014
  5. Mitochondrial biogenesis- pharmacological approaches. – PubMed – NCBI

 

CoQ10 – Obesity

  1. Evaluation of antioxidant systems (coenzyme Q10 and total antioxidant capacity) in morbid obesity before and after biliopancreatic diversion

 

CoQ10 – Diabetic Peripheral Neuropathy

  1. Diabetic neuropathic pain development in type 2 diabetic mouse model and the prophylactic and therapeutic effects of coenzyme Q10
  2. The effect of ubiquinone in diabetic polyneuropathy: a randomized double-blind placebo-controlled study. – PubMed – NCBI
  3. Mechanisms of disease – The oxidative stress theory of diabetic neuropathy – 2008

 

CoQ10 – Statins

  1. Coenzyme Q(10) and statin myalgia: what is the evidence? – PubMed – NCBI
  2. Coenzyme Q10 Supplementation for the Treatment of Statin Induced
  3. Effect of coenzyme q10 on myopathic symptoms in patients treated with statins. – PubMed – NCBI
  4. Effects of coenzyme Q10 supplementation (300 mg:day) on antioxidation and anti-inflammation in coronary artery disease patients during statins therapy
  5. Effects of ubiquinone (coenzyme Q10) on myopathy in statin users. – PubMed – NCBI
  6. Pharmacogenetics of Statin-Induced Myopathy – A Focused Review of the Clinical Translation of Pharmacokinetic Genetic Variants
  7. Protective effects of coenzyme Q10 and L-carnitine against statin-induced pancreatic mitochondrial toxicity in rats – 2017
  8. Effects of coenzyme Q10 supplementation (300 mg:day) on antioxidation and anti-inflammation in coronary artery disease patients during statins therapy. – 2013
  9. CoQ10 and L-carnitine for Statin Myalgia?
  10. CYP2D6*4 polymorphism is associated with statin-induced muscle effects. 2007 – PubMed – NCBI

 

CoQ10 – Liposomal Product Formulations

  1. Getting into the brain – liposome-based strategies for effective drug delivery across the blood–brain barrier – 2016

Emphasis on Education

 

Accurate Clinic promotes patient education as the foundation of it’s medical care. In Dr. Ehlenberger’s integrative approach to patient care, including conventional and complementary and alternative medical (CAM) treatments, he may encourage or provide advice about the use of supplements. However, the specifics of choice of supplement, dosing and duration of treatment should be individualized through discussion with Dr. Ehlenberger. The following information and reference articles are presented to provide the reader with some of the latest research to facilitate evidence-based, informed decisions regarding the use of conventional as well as CAM treatments.

 

For medical-legal reasons, access to these links is limited to patients enrolled in an Accurate Clinic medical program.

 

Should you wish more information regarding any of the subjects listed – or not listed –  here, please contact Dr. Ehlenberger. He has literally thousands of published articles to share on hundreds of topics associated with pain management, weight loss, nutrition, addiction recovery and emergency medicine. It would take years for you to read them, as it did him.

 

For more information, please contact Accurate Clinic.

 

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