Coenzyme Q10 More information

A Continuation of the Review of Essential Functions and Clinical Trials

Research suggests a role for CoQ10 in conditions related to oxidative stress.

Hypertension

The benefits of CoQ10 supplementation in hypertensive patients with deficiencies of succinate dehydrogenase CoQ10 reductase activity were investigated by Yamagami et al. [26, 27] The researchers proposed that improving bioenergetics by repleting CoQ10 deficiency states may reduce blood pressure. After repletion of CoQ10 stores, they reported an increase in the specific activity of CoQ10 with reductions in systolic and diastolic pressure in selected patients.

Other investigators studied the effects of CoQ10 supplementation on both untreated and treated hypertensive patients, reporting statistically significant reductions in systolic and diastolic pressure in the majority of patients. In a double-blind, placebo-controlled study involving 20 hypertensive subjects with low serum CoQ10 concentrations, Greenberg et al. [4] reported significant reductions in diastolic and systolic blood pressure from the administration of CoQ10 in doses of 33.3 mg three times daily compared to placebo.

In a randomized, double-blind trial of hypertensive patients with coronary artery disease (CAD), the effects on blood pressure and insulin resistance of CoQ10 (60 mg twice daily) was compared to vitamin B complex. [28] After an eight-week period, reductions were reported in the following indices: systolic and diastolic blood pressure; lipid peroxidase; fasting and 2-hour plasma insulin; blood glucose; and serum triglyceride levels. Moreover, an increase in high density lipoprotein (HDL)-cholesterol and vitamins A, C, and E, and beta carotene serum concentrations in the CoQ10 treated group were observed. However, an increase in vitamin C and beta carotene serum concentrations were the only changes seen in the vitamin B complex group.

In an open-label study, doses of CoQ10 to maintain a serum level >2.0 µg/mL were added to standard antihypertensive drug therapy in 109 symptomatic patients with essential hypertension. The average daily dose of CoQ10 was 225 mg. Gradual improvements in functional and clinical status were observed within the first six months necessitating a decrease in antihypertensive drug therapy. Fifty-one percent of the patients were able to use 1 3 fewer reduce antihypertensive drugs. Overall, NYHA functional class improved from a mean of 2.40 to 1.36 (p<0.001).[29]

In an uncontrolled study, the antihypertensive effects of CoQ10 in doses of 50 mg twice daily were studied in 26 patients with essential hypertension after a wash-out period following the discontinuation of all antihypertensive medications. After supplementation for 10 weeks, both diastolic and systolic blood pressure were significantly reduced (p<0.001) and serum CoQ10 concentrations were increased. In addition, serum total cholesterol decreased and serum HDL-cholesterol increased significantly.30 Although available human data suggest a possible adjunctive role of CoQ10 in essential hypertension, additional controlled studies are needed.

Myocardial Protection in Open Heart Surgery/ Arrhythmias:

In a randomized, placebo-controlled trial, 40 patients undergoing elective coronary artery bypass graft (CABG) received either CoQ10 150 mg daily for seven days prior to surgery or a placebo. The serum concentrations of creatine kinase (CK) and malondialdehyde (MDA), post-operative markers of oxidative damage, in the treatment group were significantly lower than in the control group during the recovery period (p<0.05). In addition, there was a significantly lower incidence of ventricular arrhythmias as well as a lower mean dose of dopamine required to maintain stable hemodynamics in the treatment group.[31]

The myocardial protective effects of CoQ10 were evaluated in patients with low serum CoQ10 concentrations, low cardiac index (CI), and low left ventricular ejection fraction (LVEF) in a placebo-controlled trial by Judy et al.32 The CoQ10 treatment group received doses of 100 mg daily for 14 days prior to CABG surgery and 30 days after surgery. Presurgical CoQ10 supplementation increased both serum and myocardial CoQ10 concentrations during surgery and myocardial ATP. CI and LVEF were significantly improved (p <0.01) after cardiac cooling in the CoQ10 group compared to the placebo group. The recovery course was 3 5 days and uncomplicated in the CoQ10 group, and 15 30 days and complicated in the placebo-control group. The authors concluded that the administration of CoQ10 may improve surgical recovery and lessen the magnitude of surgical insult in heart surgery.

Investigation of the use of intravenous and intracoronary CoQ10 administration was conducted to evaluate the direct-scavenging, free-radical activity of CoQ10 in a controlled trial of 24 patients undergoing cardiac valve replacement. The myocardial protective effects of CoQ10 in 12 patients were compared against an equal number of control subjects. In the CoQ10 group, plasma MDA and cardiac isoenzyme CK (CK-MB) concentrations were significantly lower. Erythrocyte superoxide dismutase (SOD) activity indicative of hydroxyl radical scavenging was significantly higher in the CoQ10 group compared to controls. The authors concluded that CoQ10 plays a protective role during cardiac valve replacement by directly scavenging hydroxyl radicals, thus acting as an antioxidant and membrane stabilizer. [3]

Doxorubicin Cardiotoxicity Prophylaxis:

Doxorubicin (Adriamycin) is an anthracycline used in cancer chemotherapy. Since doxorubicin inhibits CoQ10-dependent enzymes, pretreatment with CoQ10 may mitigate its cardiotoxic effects. Proposed mechanisms of cardioprotection involve the inhibition of doxorubicin-induced lipid peroxidation and scavenging free radicals.[4] Therefore, CoQ10 may have a potential role in the prevention of doxorubicin-induced cardiotoxicity.

Cortes et al.[34] studied the early detection of cardiotoxicity in doxorubicin-treated patients, using CoQ10 in doses of 50 mg. daily. The mean systolic interval (STI) increased gradually with increasing cumulative doses of doxorubicin in the control group. However, the mean STI improved, or shortened, with increasing cumulative doses of doxorubicin (200 500 mg./m[2]) in the CoQ10 group, resulting in a decreased incidence of cardiac dysfunction. Further studies are warranted to establish the role of CoQ10 in doxorubicin-induced cardiotoxicity.

Cancer

Numerous studies have noted the incidence of CoQ10 deficiency in a variety of cancers including breast, lung, prostate, pancreatic and colon cancer.[35-37] In an open-label study of 32 breast cancer patients with metastases to axillary lymph nodes, 90 mg./day of CoQ10 plus high-dose antioxidant therapy with vitamin C, vitamin E, beta carotene, selenium, and omega-3 and omega-6 fatty acids were given in addition to conventional surgery and chemotherapy. During the 18-month study period, none of the patients showed signs of further metastases and six of the 32 patients had partial tumor regression.38,39 Further research by these same investigators on three of these six patients, with doses of CoQ10 increased to 390 mg./day, documented remission throughout the 3 5 year study.[4]

Periodontal Disease

Decreased serum and gingiva levels of CoQ10 have been documented in patients with periodontal disease.[41-43] In fact, a small double-blind placebo-controlled trial conducted by Wilkinson et al. found CoQ10 50 mg./day for 21 days to significantly improve several clinical aspects of periodontal disease, including inflammation, pocket depth, and tooth mobility.[44]

Immune Modulation

Studies have demonstrated that the degree of CoQ10 deficiency is correlated with the severity of immune compromised diseases. Patients with acquired immune deficiency syndrome (AIDS) showed statistically significant lower CoQ10 serum concentrations than AIDS-related complex (ARC) patients, who in turn had lower levels than healthy subjects.[45] A clinical case series of eight adult patients treated with 60 mg./day of CoQ10 reported significant increases in serum IgG levels over 1 4 months.[46]

An open, non-comparative pilot study of 14 healthy adults treated with 100 mg./day of CoQ10 for two months showed significant increases in T4/T8 ratios, indicating stimulation of the immune system.[47] Further investigation evaluating the effectiveness of CoQ10 in the treatment of immune deficiency diseases is warranted.

Neurodegenerative Diseases

Research suggests a strong correlation between human myotonic dystrophic conditions and defects in mitochondrial functions, energy metabolism, and oxidative damage.[48] In two double-blind, placebo-controlled trials in patients with progressive muscular dystrophy or neurogenic atrophic disease, treatment with CoQ10 in doses of 100 mg./day for three months was associated with improvements in cardiac output and stroke volume in addition to subjective improvements in exercise tolerance, leg pain, and fatigue. [49]

Formulations and Dosage

Exogenous supplies of CoQ10 are found in foods such as fish and fish oils, organ meats and germ of whole grains. However, in some cases dietary intake may be inadequate to meet the body s needs. The average diet is estimated to provide approximately 10 mg./day of CoQ10.

Commercially available CoQ10 is produced by the fermentation of beets and sugar cane, using special strains of yeast. Dosage forms currently available include powder-filled capsules, powder-based tablets, softgel capsules, fully solubilized softgel capsules, chewable wafers, intravenous solution, and intra-oral spray. Assessment of the bioavailability of various dosage formulations demonstrated that the fully solubilized softgel capsule (Q-gel) achieved the highest serum CoQ10 concentration.[50]

Doses of 30 60 mg./day (approximately 1 mg./kg of body weight) are generally recommended to prevent CoQ10 deficiency and to maintain normal serum concentrations of 0.7 1.0 µg/mL. However, thera-peutic doses of 100 200 mg./day are advocated for the treatment of chronic heart disease. These higher doses may achieve serum concentrations of 2.0 3.0 µg/mL, reported by some investigators to have a positive impact on cardiovascular health. Doses used in the treatment of breast cancer range from 90 390 mg./day (TABLE 2). Divided doses are recommended to minimize adverse effects when doses exceed 100 mg/day. Maximum absorption of CoQ10 can be achieved if taken with meals that contain fat.[51]

Adverse Effects

Documented adverse effects associated with the use of CoQ10 in humans have been minor and include epigastric discomfort (0.39%), appetite suppression (0.23%), nausea (0.16%) and diarrhea (0.12%).[4] These complaints are dose-related and minimized with dose reduction and/or dose division. Higher than usual doses exceeding 300 mg./day have been associated with elevated serum LDH and SGOT levels, however no hepatic toxicity has been observed. Late night administration has also been reported to cause insomnia.[51]

Drug Interactions

The concomitant administration of CoQ10 with 3 hydroxy 3 methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors has been shown to interfere with the endogenous synthesis of CoQ10. HMG-CoA reductase inhibitors block the synthesis of mevalonic acid, a precursor to cholesterol and to CoQ10. Watts et al. demonstrated a significant inverse relationship between CoQ10 levels and the dose of simvastatin (p<0.001). However, the clinical significance of these findings has not been determined and the need for CoQ10 supplementation when using these agents has not been adequately studied.[52,53]

Table 2 CoQ10 Recommended Intake
Disease	Usual Doses
Cardiovascular Chronic Heart Failure Stable Angina Hypertension Cardiotoxicity Cardiac Surgery/Arrhythmia	100 200 mg. 150 200 mg. 100 200 mg. 50 mg. 100 200 mg.
Miscellaneous Breast Cancer Periodontal Disease Immunocompromised	90 390 mg. 50 mg. 100 mg.

Beta-blockers have shown to decrease endogenous serum CoQ10 levels by inhibiting CoQ10-dependent enzymes.[51] Furthermore, CoQ10 supplementation has been reported to reduce insulin requirements in diabetes mellitus. Additionally, some oral hypoglycemic agents including glyburide, acetohexamide, and tolazamide have also been shown to decrease endogenous CoQ10 levels. Therefore, diabetic patients taking CoQ10 may require dosage adjustments of hypoglycemic agents.[54]

Caution should also be exercised with the concomitant use of CoQ10 and warfarin due to the potential antagonism of anticoagulant activity, based on the structural similarity of CoQ10 to vitamin K. Case reports have documented decreases in the International Normalized Ratio (INR) in warfarin-stabilized patients after administration of CoQ10.[55] Clinicians should therefore be aware of this potential interaction and monitor INR closely. (See TABLE 3.)

Table 3 Drug Interactions with CoQ10
Drug	Effect	Mechanism of Action
HMG-CoA Reductase Inhibitors	Decreases Endogenous CoQ10 Levels	Blocks Pathway to Produce CoQ10
Beta-Blockers	Decreaces Endogenous CoQ10 Levels	Inhibits Enzymes to Produce CoQ10
Warfarin	Decreases INR	CoQ10 Structurally Similar to Vitamin K Increase Clotting Factors.*
Oral Hypoglycemics (glyburide, acetohexamide, tolazamide)	Decreases Endogenous CoQ10 Levels	Inhibits Enzymes That Produce CoQ10
*Recommendations: Monitor INR

Contraindications

No data have evaluated the safety or toxicity of CoQ10 during pregnancy, lactation or childhood. Therefore, its use is not recommended in these patient populations. All natural products carry the potential for allergic reactions, however, to date, none have been reported with the use of CoQ10.[56]

References:

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Zhou M, Zhi Q, et al. Effects of coenzyme Q10 on myocardial protection during cardiac valve replacement and scavenging free radical activity in vitro. J Cardiovasc Surg (Torino) 1999;40(3):355-61.
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Available Pharmaceutical Grade Coenzyme Q10

Co Q10 200 mg. with Vit. E 400 IU. (30 WAFERS)

Research has confirmed deficiencies of CoQ10 in significant numbers of patients with: Heart Disease, Cancer, Diabetes Mellitus, Obesity, Hypertension, Periodontal Disease, AIDS and ARC,. While supplemental CoQ10 has been given to deficient patients, symptoms have improved; however, in most studies, relatively low doses (30-100 mg. daily) have been used.

Co Q10 100 Mg. with Tocotrieol E (30 Softgels)

Hypoallergenic. This semi-essential nutrient is a potent antioxidant and coenzyme, critical to the successful production of bioenergy via the electron transport system in the cell.

Co Q10 100 Mg. with Tocotrieol E (60 Softgels)

Hypoallergenic. This semi-essential nutrient is a potent antioxidant and coenzyme, critical to the successful production of bioenergy via the electron transport system in the cell.

Co Q10 Plus 100 mg. (30 Softgel)

Co-Q 10 is a co-enzyme, which has antioxidant properties, is important for coronary health and has beneficial effect on many other functions.

Each capsule contains: Coenzyme Q-10 100 mg., Vitamin E (natural E as mixed Tocopherols) 100 IU., Rice Brand oil 185 mg., Yellow beeswax 20mg., Beta Carotene 7 mg.

A necessary enzyme in the body located in the mitochondria of cells, and found mostly in the cardiac muscle tissue, as well as skeletal muscle tissue, liver, kidney and reproductive organs. It is important in the formation of ATP (adenosine triphosphate) which produces energy at the cellular level in the body and is essential for cardiac performance.

Assists in preventing heart disorders including, cardiomyopathy, myocardial ischemia, angina, hypertension and congestive heart failure.
Powerful antioxidant properties.
Co-Q 10 Plus is contained in a base of rice brand oil, rich in Tocotrienols, which helps maintain healthy cholesterol levels, with added Vitamin E and Beta Carotene.
May enhance the immune system.
Co-Q 10 works synergistically with vitamin E for better results.

Co-Q 10 Plus contains Rice Brand Oil, which is significantly better for transport and absorption than dry based materials. It is rich in important Tocotrienols, which are a very important part of the Vitamin E family, with a unique isoprene” tail.

Vitamin E has been shown in numerous studies to be important in cardio-vascular health and have beneficial antioxidant properties.

Desiccant pads are included, as in all Montiff s highest quality products, to insure optimal freshness.

Deficiencies have been reported in patients with cardiac disorders, cancer, hypertension, diabetes mellitus, periodontal disease, muscular dystrophy and AIDS.

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