By Dónal P. O’Mathúna, PhD
Diabetes remains a serious health problem throughout the world. In the United States, its prevalence has increased by more than 50% over the last 10 years, and it is predicted to increase by another 165% over the next 50 years.1 Although diabetes occurs more commonly in older people, the increased incidence is expected to be most dramatic among working-age people, leading to huge social and economic implications. Currently, more than 17 million Americans have this condition, with the vast majority having Type 2 diabetes, for which obesity is a major determinant.
Treatment of diabetes and its complications costs the United States $132 billion annually. Cardiovascular disease is the principal complication, and the leading cause of death.2 In addition, diabetes is the leading cause of kidney failure, adult blindness, and amputations.1 While increasing physical activity and reducing calorie consumption remain important interventions in preventing and treating the condition, many people are looking to dietary supplements for additional help. Coenzyme Q10 (CoQ10) is one of the supplements commonly recommended for those with diabetes.
Mitochondrial Diabetes
A number of problems can underlie the development of Type 2 diabetes. Much research has focused on problems with insulin sensitivity in peripheral tissue, but there also can be dysfunction in the pancreatic beta-cells.3 One form of beta-cell dysfunction can be traced to mitochondrial problems, which have been cited as rationale for the potential beneficial effects of CoQ10. This connection originally was proposed based on observations that Type 2 diabetes appeared to be transmitted maternally.4
Although almost all genetic material is transmitted to offspring from both parents, all people receive a small amount of DNA exclusively from their mother’s mitochondria (mtDNA). Controlled studies have not supported the original hypothesis that all Type 2 diabetes is maternally transmitted, but at least some cases have been shown to be caused by mutations in mtDNA.4 Mitochondria are known to play a role in regulating insulin secretion in beta- cells. Also, while mitochondrial myopathies have been associated primarily with neurodegenerative diseases, diabetes often can be a complicating factor. A specific mtDNA mutation labeled 3243 leads to Type 2 diabetes and deafness.5 While its incidence among all diabetic patients is well under 1%, 1.5% of the Japanese general population carries the defect.4
Mechanism of Action
Mitochondria replenish the chemical energy of cells by generating a molecule called adenosine triphosphate (ATP). CoQ10 plays a vital role in a number of complexes involved in this process.6 The biochemical background for CoQ10 was reported in this newsletter recently.7 Administration of CoQ10 has thus been proposed to compensate for the effects of mtDNA mutations, which lead to fewer mitochondria and less mtDNA in those that are made. This has been shown to negatively affect glucose-stimulated insulin release.3 In addition, CoQ10 is a more powerful antioxidant than vitamin E and may be beneficial in diabetes as a means of reducing cardiovascular damage caused by free radicals and superoxide.2
Clinical Studies
The earliest clinical trial was conducted after several patients with Type 1 diabetes reported reducing their dose of insulin after initiating CoQ10 therapy. In a double-blind study, 34 subjects were randomly assigned to receive placebo or 100 mg CoQ10 daily.8,9 Subjects adjusted their insulin doses based on home monitoring of glucose levels. After 12 weeks, there were no significant differences between the groups in total insulin dose, overall glycemic control, cholesterol levels, or general well-being.
Another trial was conducted with subjects with the 3243 mutation in mtDNA.5 In addition to diabetes and a family history of Type 2 diabetes, symptoms included impaired hearing, mitochondrial encephalomyopathy, lactic acidosis, and recurrent headaches. This open study observed 11 subjects who received between 30 and 210 mg CoQ10 daily for 3-5 months. Subjects reported reductions in fatigue, heart palpitations, and leg paresthesia, all suggesting improvements in mitochondrial metabolism. However, no improvements were reported in glycemic parameters.
An open trial involved 76 subjects with the 3243 mtDNA mutation who presented with a family history of Type 2 diabetes, deafness, and various degrees of glucose intolerance.10 Fifty subjects received 150 mg CoQ10 daily for three years and 26 matched controls received no intervention. For the first three months, no significant differences existed between the two groups. After three years, the condition of the control group had progressively worsened while those receiving CoQ10 showed significantly less deterioration in insulin secretion (P < 0.02), deafness (P < 0.02), and exercise tolerance (P < 0.001). No significant differences were found for the incidence of diabetic retinopathy, nephropathy, neuropathy, or any other chronic diabetic symptom.
A randomized, double-blind, placebo-controlled trial enrolled 23 subjects with Type 2 diabetes.11 The active arm of the trial received 100 mg CoQ10 bid for six months. Serum CoQ10 levels rose more than threefold, but no significant differences were found in glycemic control, blood pressure, or lipid levels.
An additional study focused on the cardiovascular complications of Type 2 diabetes.12 Forty subjects with diabetes and dyslipidemia were randomly assigned to receive placebo or CoQ10 (100 mg bid) for 12 weeks. Peripheral circulation was assessed using brachial artery ultrasonography. Resting blood flow and endothelial function were significantly improved in those receiving CoQ10 (P = 0.005). No significant changes were found in serum glucose or lipid levels, antioxidant capacity, or blood pressure.
A study by the same research group randomly divided 74 Type 2 diabetes patients with dyslipidemia into four groups.13 Subjects received either fenofibrate (200 mg daily), CoQ10 (100 mg bid), fenofibrate plus CoQ10 (200 mg/200 mg daily), or placebo for 12 weeks. Fenofibrate is the most potent member of a class of drugs used to treat cardiovascular disease in high-risk patients, including diabetics. Those receiving CoQ10 alone had significantly reduced blood pressure, both systolic (P = 0.021) and diastolic (P = 0.048), and improved glycemic control as measured by reduced glycated hemoglobin (HbA1c) levels (P = 0.032). Fenofibrate alone significantly improved all serum lipid levels, but no significant lipid level changes were found with CoQ10 or either of the two other groups.
The same researchers randomly divided 80 Type 2 diabetes patients with dyslipidemia into the same four groups as above.2 Fenofibrate alone significantly increased HDL-cholesterol levels and lowered all other serum lipid levels (P < 0.001); glucose levels were unchanged. CoQ10 alone did not significantly change glucose, insulin, or any lipid levels. However, it did lower blood pressure and HbA1c levels (P < 0.05). In forearm vasodilatation tests, only the combined therapy led to normalized blood flow. Significant results were found with three of the four different agonists used in the vasodilation tests (P = 0.001, 0.016, 0.006).
Adverse Effects
No adverse effects were reported in the clinical trials discussed above. Other studies have reported mild adverse effects, primarily GI disturbances. The authors of one study recommended prudent monitoring of renal function of patients taking high CoQ10 doses after two of 15 subjects had abnormal urinalyses.14
Drug Interactions
CoQ10 is chemically similar to vitamin K and may have pro-coagulant activity, with four cases of decreased effectiveness of warfarin reported and thought to be related to CoQ10.15 The HMG CoA reductase inhibitors (statins) inhibit cholesterol and CoQ10 synthesis, leading to lower CoQ10 levels. Whether this is clinically significant is unknown. CoQ10 may have additive effects with other hypoglycemic or anti-hypertensive agents requiring caution and close monitoring.15
Formulation
CoQ10 supplements are formulated as oil-based capsules, powder-filled capsules, tablets, wafers, and soft-gel capsules containing microemulsions.16 The highly lipophilic nature of CoQ10 makes its absorption poor, highly variable, and strongly dependent on the contents of the stomach. It is best taken with food, especially fat-rich foods. Solubilized formulations have been found to have better bioavailability than powders.7
Conclusion
A relatively small number of trials have examined the effectiveness of CoQ10 supplementation in diabetes. The one trial with Type 1 diabetes found no benefit, and all other trials involved Type 2 diabetes. Cases of diabetes due to mtDNA mutations appear to respond well to CoQ10, although controlled trials are needed in this area. Results of controlled clinical trials with general forms of Type 2 diabetes have been somewhat variable. However, one research group has published three reports indicating improvements in glycemic control and cardiovascular parameters. The most significant improvements were found when CoQ10 was combined with fenofibrate.
Recommendation
Given the lack of adverse effects, CoQ10 can be recommended for patients with Type 2 diabetes even though a large number of studies have not been conducted in this area. There is evidence from other groups of patients that CoQ10 can be beneficial for vascular function and blood pressure.17 Given the importance of reducing cardiovascular complications in diabetes, this benefit alone warrants further study. Patients whose diabetes is already stabilized should have their glucose levels monitored if they begin using CoQ10. Practitioners should offer help in evaluating the quality of available brands, especially since these supplements can be costly. Patients should be actively monitored for potential adverse effects or drug interactions.
Dr. O’Mathúna is a lecturer at the School of Nursing, Dublin City University, Ireland.
References
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2. Playford DA, et al. Combined effect of coenzyme Q10 and fenofibrate on forearm microcirculatory function in type 2 diabetes. Atherosclerosis 2003;168:169-179.
3. Lamson DW, Plaza SM. Mitochondrial factors in the pathogenesis of diabetes: A hypothesis for treatment. Altern Med Rev 2002;7:94-111.
4. Alcolado JC, et al. Maternal transmission of diabetes. Diabetic Med 2002;19:89-98.
5. Suzuki Y, et al. Diabetes mellitus associated with 3243 mitochondrial tRNA(Leu(UUR)) mutation: Clinical features and coenzyme Q10 treatment. Mol Aspects Med 1997;18(Suppl):S181-S188.
6. Beal MF. Coenzyme Q10 administration and its potential for treatment of neurodegenerative diseases. Biofactors 1999;9:261-266.
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8. Andersen CB, et al. The effect of coenzyme Q10 on blood glucose and insulin requirement in patients with insulin dependent diabetes mellitus. Mol Aspects Med 1997;18(Suppl):S307-S309.
9. Henriksen JE, et al. Impact of ubiquinone (coenzyme Q10) treatment on glycaemic control, insulin requirement and well-being in patients with Type 1 diabetes mellitus. Diabet Med 1999;16:312-318.
10. Suzuki S, et al. The effects of coenzyme Q10 treatment on maternally inherited diabetes mellitus and deafness, and mitochondrial DNA 3243 (A to G) mutation. Diabetologia 1998;41:584-588.
11. Eriksson JG, et al. The effect of coenzyme Q10 administration on metabolic control in patients with type 2 diabetes mellitus. Biofactors 1999;9:315-318.
12. Watts GF, et al. Coenzyme Q10 improves endothelial dysfunction of the brachial artery in Type II diabetes mellitus. Diabetologia 2002;45:420-426.
13. Hodgson JM, et al. Coenzyme Q10 improves blood pressure and glycaemic control: A controlled trial in subjects with type 2 diabetes. Eur J Clin Nutr 2002;56: 1137-1142.
14. Shults CW, et al. Absorption, tolerability, and effects on mitochondrial activity of oral coenzyme Q10 in parkinsonian patients. Neurology 1998;50:793-795.
15. Coenzyme Q-10. Available at: www.naturaldatabase.com. Accessed on April 16, 2004.
16. Coenzyme Q10 (CoQ10). In: PDR for Nutritional Supplements. Montvale, NJ: Medical Economics; 2001:103-106.
17. Hodgson JM, Watts GF. Can coenzyme Q10 improve vascular function and blood pressure? Potential for effective therapeutic reduction in vascular oxidative stress. Biofactors 2003;18:129-136.
O'Mathuna DP. Coenzyme Q10 for diabetes. Altern Med Alert 2004;7(6):61-64.
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