CoQ10: The State of the Science in Diabetes
Coenzyme Q10 (CoQ10) is a vital nutrient in the human body. CoQ10 is widely distributed in the human body and serves as a cofactor for the production of cellular energy in most human cells. As the name implies, a coenzyme is a factor that helps the function of an enzyme; enzymes are small proteins in the body that carry out nearly every chemical reaction. CoQ10 is made in our body and therefore for most people it is not essential to eat CoQ10 or take supplements, however CoQ10 status can become depleted because of various health conditions, medications and environmental factors.
How CoQ10 “Works”
The majority of cellular energy comes from the breakdown of glucose (sugar) or fat. Although this process occurs in several compartments inside of each cell, the final CoQ10-requiring processes occur inside of a small organelle called the mitochondria. The mitochondria is called the “powerhouse of the cell” because it rapidly moves, or shuttles, molecules which drives the production of cellular energy (a molecule called ATP). In people with diabetes, the level of glucose is greater than what each mitochondria can handle and as a result energy production inside of the cell can’t keep up with the demand, and the process stalls. Imagine a relay race where 50 runners are all trying to hand their batons to a single runner!
This phenomenon has been researched extensively by diabetes researcher Michael Brownlee. The availability of CoQ10 limits the speed at which glucose can be processed into energy by the cell. Without CoQ10, this energy gets misdirected and causes oxidation inside of the mitochondria. The oxidative reactions deplete important antioxidants contributing to the development of complications in some tissues. In this way, CoQ10 acts as an antioxidant.
This model of action and prevention of metabolic abnormalities by CoQ10 is supported by research in rare types of diabetes caused by genetic mutations in the mitochondria. In this genetic form of diabetes CoQ10 supplementation has been shown to be effective in reducing blood sugar and improving insulin secretion. While these findings do not necessarily apply to individuals without this genetic form of the disease, mitochondrial changes are present in other forms of diabetes too, as reviewed by Lamson and Plaza.
CoQ10 in Diabetes and Cardiovascular Disease
CoQ10 has been tested in clinical trials and found beneficial in several medical conditions that have relevance for a person with diabetes, including diabetes itself, insulin resistance, high blood pressure, congestive heart failure and endothelial dysfunction (an abnormality of the lining of blood vessels that reduces the ability of the vessel to open, or dilate, properly). CoQ10 has not been tested for prevention of many of these conditions; although improving blood vessel function may prevent high blood pressure and atherosclerosis of the vessels, prevention of atherosclerosis and hypertension has not been demonstrated by CoQ10 per se.
The most consistent research on CoQ10 is in the treatment of high blood pressure, with at least five clinical trials demonstrating improvements. One of my favorite descriptions of the potential of CoQ10 in hypertension is the article by Lansjoen et al. in which they describe their experience with the clinical use of CoQ10. In this article, the author described experience with over 109 patients with high blood pressure. Reductions in blood pressure were achieved allowing reductions in blood pressure medications in over half of the patients. The average CoQ10 dose used was 225 mg per day and the average treatment time was 4.4 months. As always, you should develop a plan you’re your physician before implementing any new treatment for high blood pressure because stopping blood pressure medications can result in dangerous spikes in blood pressure; CoQ10 appears to be beneficial in high blood pressure but it does not act rapidly and therefore monitoring by your physician is important to ensure safety.
Less research is available directly evaluating the effects of CoQ10 on blood sugar or insulin sensitivity. However a few studies do exist. The largest, best-designed study of CoQ10 in diabetes was performed by Hodgson et al. and published in 2002. It is important to note that although the reduction in both blood glucose and blood pressure was significant in this study, they were modest reductions: 6 mmHg in systolic blood pressure (the upper number), 3 mmHg reduction in diastolic blood pressure (the bottom number) and 0.4% reduction in hemoglobin A1c. The dose of CoQ10 in this study was 200 mg/day.
Congestive heart failure is a condition in which the heart no longer contracts with enough force to push out all of the blood that enters its chambers; medically this is referred to as a reduced ejection fraction. Because the heart is an energy-demanding organ, and because the force of contraction is reduced in congestive heart failure, several researchers have evaluated the effects of CoQ10 on force of contraction and general function in patients with heart failure - with mixed results.
o Khatta et al. studied 55 patients with congestive heart failure receiving CoQ10 (200mg/day) for six months and found no improvement in ejection fraction with only a minority of patients reporting improved symptoms .
o In an earlier study, Morisco et al. studied CoQ10 (200 mg/day versus placebo) for one year in 322 patients with congestive heart failure; reduced hospitalization rates and reduced rates of acute complications were among the positive results of this study .
o Finally Hofman-Bang et al. also studied CoQ10 in heart failure (100mg/day versus placebo) for a period of three months; improved exercise tolerance, ejection fraction and quality of life were among the reported positive results.
So, what’s the bottom line? CoQ10 requires more study in larger controlled trials to really establish the truth about its effects, however the available research suggests CoQ10 is likely beneficial for high blood pressure, may be beneficial for blood sugar regulation and appears to be helpful in congestive heart failure (if only by improving functional status and reducing hospitalization). Should you start taking CoQ10? Considering there are essentially no reported side effects of CoQ10 treatment and there appears to be benefit in multiple conditions that are common in people with diabetes, I frequently recommend that my patients do supplement with CoQ10. Unfortunately, CoQ10 is expensive and so the cost must always be balanced with the expected benefit.
I’ve Heard My Cholesterol Medication Depletes CoQ10? Should I Supplement?
Statin medications, commonly prescribed today for high cholesterol (and considered standard of care for cardiovascular protection in diabetes) do deplete CoQ10 levels in the body, however the significance of this reduction is unknown [17, 18]. The relationship between side effects of statin medications, long term cardiovascular health and CoQ10 has been poorly studied. In fact the medical community still does not have a good clinical trial that compares people on statins plus CoQ10 to patients on statins alone. This is unfortunate and, given the cost of both, desperately needed for both patient knowledge and physician practice.
o One study has evaluated whether blood levels of CoQ10 while on statin medications predict heart attack and other cardiac events; this study found no relationship between blood CoQ10 concentration and risk .
o A small, practice-based study evaluated the effects of CoQ10 on statin side effects. This study suggests CoQ10 may reduce side effects from statins, however patients had stopped their statin medications in this study and there was no control of patients who stopped statins and did not start CoQ10.
Although the data is still lacking regarding the significance of the reduction in CoQ10 by statin medications, I do recommend patients supplement CoQ10 when they use statin medications. It is important to note, some statin medications have an excellent track record for cardiovascular protection in patients who need them for cholesterol-lowering. They lower unhealthy, LDL cholesterol and some have anti-inflammatory effects; their benefit appears to stand despite lowering CoQ10 levels. My clinical observations suggest CoQ10 does help reduce muscle aches and fatigue associated with statin use and, until the research becomes more definitive, I will continue to recommend CoQ10 replacement.
Does the Form of CoQ10 Matter?
There are differences in absorption from different forms of CoQ10.
o A study by Singh et al. in 2005 suggested oil-based, softgel CoQ10 is more effective than crystalline CoQ10 at reducing markers of oxidative stress and raising CoQ10 levels.
o Ullman et al. compared the absorption of three different types of CoQ10 (Q-sorB, all Q, and Q Gel) and found near equivalence between all-Q and Q Gel, but both all-Q and Q Gel appeared superior to Q-sorB.
o Further study of the Q Gel formulation by Chopra et al. published in 2006 suggests the absorption of Q Gel is superior to oil-filled capsules or powder-based tablets; blood CoQ10 concentrations were 2-3 times greater from the Q Gel formulation.
Unfortunately neither patients nor physicians have good clinical trials that compare these different preparations on clinical measures like blood pressure and blood sugar control. In fact, many of the studies available were performed on crystalline, tablet preparations and although it is always tempting to purchase the newest and the best technology, sometimes sticking with the old faithful has its benefits.
Diabetes Action Funds New CoQ10 Research
Because of the need for more research, Diabetes Action is curently funding a study at Drexel University where Dr. Sinclair Smith is studying the use of CoQ10 supplements to improve circulation, energy utilization, and endurance in muscles of people with type 2 diabetes and mild PVD (peripheral vascular disease).
CoenzymeQ10 is an important cofactor for energy production in the human body and appears to offer benefits to cardiovascular health and function, including lowering blood pressure, improving exercise tolerance in patients with heart failure, possibly improving ejection fraction in heart failure, reducing hospitalization in heart failure and possibly improving blood sugar in patients with diabetes. Statin-class cholesterol-lowering medications deplete blood CoQ10 levels without question, however the effects of this depletion on cardiac health remain unknown. The preparation of CoQ10 does affect absorption, but it remains unknown how different preparations affect function and cardiac health.
In summary, CoQ10 may offer great benefit for cardiac health yet more research is needed to confirm the trials available to date and, for some patients, the cost of CoQ10 may be prohibitive. If the decision has to be made between purchasing a gym membership or buying CoQ10, I still recommend you go to the gym.
Ryan Bradley, ND, MPH February, 2007
1. Brownlee, M., The pathobiology of diabetic complications: a unifying mechanism. Diabetes, 2005. 54(6): p. 1615-25.
2. 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(5): p. 584-8.
3. 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: p. S181-8.
4. Lamson, D.W. and S.M. Plaza, Mitochondrial factors in the pathogenesis of diabetes: a hypothesis for treatment. Altern Med Rev, 2002. 7(2): p. 94-111.
5. Hodgson, J.M., 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(11): p. 1137-42.
6. Watts, G.F., et al., Coenzyme Q(10) improves endothelial dysfunction of the brachial artery in Type II diabetes mellitus. Diabetologia, 2002. 45(3): p. 420-6.
7. Eriksson, J.G., et al., The effect of coenzyme Q10 administration on metabolic control in patients with type 2 diabetes mellitus. Biofactors, 1999. 9(2-4): p. 315-8.
8. Burke, B.E., R. Neuenschwander, and R.D. Olson, Randomized, double-blind, placebo-controlled trial of coenzyme Q10 in isolated systolic hypertension. South Med J, 2001. 94(11): p. 1112-7.
9. Singh, R.B., et al., Effect of hydrosoluble coenzyme Q10 on blood pressures and insulin resistance in hypertensive patients with coronary artery disease. J Hum Hypertens, 1999. 13(3): p. 203-8.
10. Langsjoen, P., et al., Treatment of essential hypertension with coenzyme Q10. Mol Aspects Med, 1994. 15 Suppl: p. S265-72.
11. Khatta, M., et al., The effect of coenzyme Q10 in patients with congestive heart failure. Ann Intern Med, 2000. 132(8): p. 636-40.
12. Morisco, C., B. Trimarco, and M. Condorelli, Effect of coenzyme Q10 therapy in patients with congestive heart failure: a long-term multicenter randomized study. Clin Investig, 1993. 71(8 Suppl): p. S134-6.
13. Langsjoen, P.H. and A.M. Langsjoen, The clinical use of HMG CoA-reductase inhibitors and the associated depletion of coenzyme Q10. A review of animal and human publications. Biofactors, 2003. 18(1-4): p. 101-11.
14. Digiesi, V., et al., Coenzyme Q10 in essential hypertension. Mol Aspects Med, 1994. 15 Suppl: p. s257-63.
15. Yamagami, T., N. Shibata, and K. Folkers, Bioenergetics in clinical medicine. VIII. Adminstration of coenzyme Q10 to patients with essential hypertension. Res Commun Chem Pathol Pharmacol, 1976. 14(4): p. 721-7.
16. Hofman-Bang, C., et al., Coenzyme Q10 as an adjunctive in the treatment of chronic congestive heart failure. The Q10 Study Group. J Card Fail, 1995. 1(2): p. 101-7.
17. Ghirlanda, G., et al., Evidence of plasma CoQ10-lowering effect by HMG-CoA reductase inhibitors: a double-blind, placebo-controlled study. J Clin Pharmacol, 1993. 33(3): p. 226-9.
Miyake, Y., et al., Effect of treatment with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on serum coenzyme Q10 in diabetic patients. Arzneimittelforschung, 1999. 49(4): p. 324-9.
19. Stocker, R., et al., Neither plasma coenzyme Q10 concentration, nor its decline during pravastatin therapy, is linked to recurrent cardiovascular disease events: a prospective case-control study from the LIPID study. Atherosclerosis, 2006. 187(1): p. 198-204.
Langsjoen, P.H., et al., Treatment of statin adverse effects with supplemental Coenzyme Q10 and statin drug discontinuation. Biofactors, 2005. 25(1-4): p. 147-52.
21. Singh, R.B., et al., Effect on absorption and oxidative stress of different oral Coenzyme Q10 dosages and intake strategy in healthy men. Biofactors, 2005. 25(1-4): p. 219-24.
22. Ullmann, U., et al., A new Coenzyme Q10 tablet-grade formulation (all-Q) is bioequivalent to Q-Gel and both have better bioavailability properties than Q-SorB. J Med Food, 2005. 8(3): p. 397-9.
23. Chopra, R.K. and H.N. Bhagavan, On the bioequivalence and bioavailability of three coenzyme Q10 products. J Med Food, 2006. 9(1): p. 131-2; author reply 133-4.