Coenzyme Q10

Coenzyme Q10 is also called ubiquinone, because it is ubiquitous in the human body, found in the membranes of all of our cells.  In a 2018 randomized, double-blind, placebo-controlled trial, Zhang et al.¹ looked at coenzyme Q10 supplementation in 40-61 year old Chinese people with high cholesterol to see which of several risk factors for cardiovascular disease might be improved.  The dosage was 120 mg/day for 24 weeks; 60 mg twice a day after meals.  This intervention resulted in lower blood pressure after 12 and even lower after 24 weeks, compared to baseline, and also lower triglycerides and LDL cholesterol by 24 weeks.  All of the 101 participants who completed the intervention started out with at least two of the four characterizations of dyslipidemia:  high total cholesterol, LDL cholesterol, or triglycerides, or low HDL cholesterol.  Anyone with total cholesterol over 309 mg/dL or triglycerides over 395 mg/dL was not selected to participate, nor was anyone taking any drugs to lower blood pressure, cholesterol, or blood sugar.  They found that systolic and diastolic blood pressure were both lowered by more than 6%, or 9 mm Hg systolic and 6 mm Hg diastolic from an average of 167 over 103 at baseline in the intervention group, and the effects of diet and physical activity were taken into account and found to not be a factor.  The participants had been chosen from those expressing no plans for dietary or exercise modifications during the 24 weeks of the study.  A lowering of LDL cholesterol and triglycerides were not yet seen at 12 weeks, but by 24 weeks LDL cholesterol had been reduced by more than 6%, and triglycerides had been reduced by more than 12%.  Again, neither of these was affected by diet or exercise when the adjustment was performed.  The authors conclude that coenzyme Q10 may be a good choice for people wanting to reduce their risk of cardiovascular disease since it is something that is naturally produced by the body as compared to statins, which they point out have been shown to actually reduce coenzyme Q10 levels.²

 

A 2007 study by Hershey et al.³ aimed to see if CoQ10 could help with migraines in 10-17 year olds found to have low levels of it.  The participants were all migraine patients at their headache clinic.  They found that a third of the 1550 patients they tested were below .5 μg/mL for CoQ10.  75% of them had levels below 0.7 μg/mL.  They added CoQ10 supplementation to the treatment plans of all those who tested below 0.700 μg/mL, at a dose of 1 to 3 mg/kg per day.  On average the 252 patients who followed up were tested again after 97 days, and it was found that their CoQ10 levels had risen from .5 to 1.20 ± 0.59 μg/mL in a reference range of 0.21 to 1.77 μg/mL.  They reported fewer headaches and rated them as not as severe on the pediatric migraine disability assessment.  46% of the participants reported half as many headaches as they had experienced previously, and on average they went from having headaches 19.2 days per month with a range of 10 to 29 days per month down to 12.5 days per month with a range of 2 to 23 days per month.  The authors mention that other studies have had similar results in adults.  One had used a dose of 150 mg per day⁴ and another had used 150 mg twice a day with a placebo comparison.⁵  They conclude with a call for longer term studies to investigate whether patients’ levels might eventually stabilize after they have received supplementation for long enough, speculating that perhaps the treatment could be ended at some point without resulting in a return of severity of symptoms.

In a double-blind RCT, Nachvak et al. (2019) compared 100 mg/day coenzyme Q10 to placebo in rheumatoid arthritis patients for two months.  The study took place in Iran.  The severity of the rheumatoid arthritis being experienced by the study participants was evaluated with a validated tool called the DAS-28 (Vander Cruyssen et al., 2005).  22 participants completed the Nachvak et al. (2019) study in the intervention group and another 22 in the placebo group.  No adverse effects were reported.  The intervention group showed statistically significant improvement compared to placebo on the DAS-28 as well as on the counts of both swollen joints and tender joints.  As insight into the mechanism of effectiveness, the authors note that levels of serum MMP-3 (matrix metalloproteinase) were also significantly lower in the intervention group compared to placebo.  Serum MMP-3 has been found to be a marker for rheumatoid arthritis activity in synovial tissue (Kobayashi et al., 2007).

 

Nachvak et al. (2019) mentioned that they had conducted a previous study, and I was able to find this one as well (Abdollahzad et al., 2015).  The intervention was the same; a double-blind RCT compared 100 mg/day coenzyme Q10 to placebo in rheumatoid arthritis patients for two months.  Again they had 22 participants in the intervention group and another 22 in the placebo group.  This time they found that the intervention group saw an improvement in two of the markers they looked at, a significant decrease in both serum malondialdehyde (MDA) and serum tumor necrosis factor alpha (TNF-α).  Blocking TNF-α with infusions of monoclonal antibodies against is effective for improving disease activity in rheumatoid arthritis patients (Elliott et al., 1994).  Abdollahzad et al. (2015) had been looking to find a nutritional product that would have the same effect. 

 

I also looked at another study (Hosoe et al., 2007) that Abdollahzad et al. (2015) had cited when they mentioned that daily coenzyme Q10 supplementation would continue contributing to increasing serum levels over the course of two weeks, at which point it would level off and maintain the new higher level for as long as supplementation was continued.  I found this really interesting, so I took a look at the graphs that Hosoe et al., (2007) provided showing the results of their study, which had given ubiquinol, the reduced form of coenzyme Q10 (ubiquinone) at various dosages to healthy participants, either as a single dose (150 or 300 mg) or daily for four weeks (placebo, 90, 150, or 300 mg).  The graphs showed plasma ubiquinol, and they looked similar in shape for the different doses, they just went up higher for higher doses.  What I found interesting was that for the single dose, the plasma levels went up to a sharp peak about six hours after ingestion, and then dropped down to an intermediate level where they stayed for the rest of the day before gradually falling over the second day.  The levels were still elevated compared to baseline at 48 hours after ingestion, the last measurement that was taken for the single dose groups.  For the four week daily groups, the levels were measured on days 0 (prior to ingestion), 1, 14, 28, and 42, in the mornings, prior to the daily dose.  On the graphs, the levels look at lot higher on day 14 than they had been on day 1, which was similar to the the levels seen in the single dose graph.  On day 28 they were even a little higher.  This was the last day that they took the daily dose.  On day 42, two weeks after they had stopped taking the ubiquinol, their levels were still elevated compared to baseline, about where the single dose group had been after two days.  Again, the higher dose graphs had a similar shape, they were just higher.  Six months after the last dose, they measured plasma ubiquinol levels in 11 of the participants who had been taking 300 mg/day, and found that they were back at baseline.  The authors take this as indication that the supplementation regimen had not interfered with the body’s ability to make its own ubiquinol. 

 

Getting back to rheumatoid arthritis, ginger supplementation (1500 mg/day for 12 weeks) was also shown to result in significant improvement on the DAS-28 score, by Aryaeian et al. (2019).  This was a double-blind, placebo-controlled RCT with 63 participants.  I was wondering what they would use for placebo, since ginger is a pretty pungent herb.  Turns out they put the placebo capsules into a box of ginger powder for two weeks so they would smell like ginger.  The study also found significant effects on expression of several genes they were looking at to see if they could be involved in the mechanism of effectiveness. 

 

References

 

Abdollahzad, H., Aghdashi, M. A., Asghari Jafarabadi, M., & Alipour, B. (2015). Effects of Coenzyme Q10 Supplementation on Inflammatory Cytokines (TNF-α, IL-6) and Oxidative Stress in Rheumatoid Arthritis Patients: A Randomized Controlled Trial. Archives of Medical Research, 46(7), 527–533. 

 

Aryaeian, N., Shahram, F., Mahmoudi, M., Tavakoli, H., Yousefi, B., Arablou, T., & Jafari Karegar, S. (2019). The effect of ginger supplementation on some immunity and inflammation intermediate genes expression in patients with active Rheumatoid Arthritis. Gene, 698, 179–185. 

 

Elliott, M. J., Maini, R. N., Feldmann, M., Kalden, J. R., Antoni, C., Smolen, J. S., Leeb, B., Breedveld, F. C., Macfarlane, J. D., Bijl, H., & et. al. (1994). Randomised double-blind comparison of chimeric monoclonal antibody to tumour necrosis factor alpha (cA2) versus placebo in rheumatoid arthritis. Lancet (London, England), 344(8930), 1105–1110. 

 

Hosoe, K., Kitano, M., Kishida, H., Kubo, H., Fujii, K., & Kitahara, M. (2007). Study on safety and bioavailability of ubiquinol (Kaneka QH ™) after single and 4-week multiple oral administration to healthy volunteers. Regulatory Toxicology and Pharmacology, 47(1), 19–28. 

 

Kobayashi, A., Naito, S., Enomoto, H., Shiomoi, T., Kimura, T., Obata, K., Inoue, K., & Okada, Y. (2007). Serum levels of matrix metalloproteinase 3 (stromelysin 1) for monitoring synovitis in rheumatoid arthritis. Archives of Pathology & Laboratory Medicine, 131(4), 563–570. 

 

Nachvak, S. M., Alipour, B., Mahdavi, A. M., Aghdashi, M. A., Abdollahzad, H., Pasdar, Y., Samadi, M., & Mostafai, R. (2019). Effects of coenzyme Q10 supplementation on matrix metalloproteinases and DAS-28 in patients with rheumatoid arthritis: a randomized, double-blind, placebo-controlled clinical trial. Clinical Rheumatology, 38(12), 3367–3374. 

 

Vander Cruyssen, B., Van Looy, S., Wyns, B., Westhovens, R., Durez, P., Van den Bosch, F., Veys, E. M., Mielants, H., De Clerck, L., Peretz, A., Malaise, M., Verbruggen, L., Vastesaeger, N., Geldhof, A., Boullart, L., & De Keyser, F. (2005). DAS28 best reflects the physician’s clinical judgment of response to infliximab therapy in rheumatoid arthritis patients: validation of the DAS28 score in patients under infliximab treatment. Arthritis Research & Therapy, 7(5), R1063–R1071.

 

Zhang P, Yang C, Guo H, et al. Treatment of coenzyme Q10 for 24 weeks improves lipid and glycemic profile in dyslipidemic individuals. Journal of clinical lipidology. 2018;12(2):417. 

Banach M, Serban C, Ursoniu S, et al. Statin therapy and plasma coenzyme Q10 concentrations—A systematic review and meta-analysis of placebo-controlled trials. Pharmacological Research. 2015;99:329-336. 

Hershey AD, Powers SW, Vockell A-LB, et al. Coenzyme Q10 Deficiency and Response to Supplementation in Pediatric and Adolescent Migraine. Headache: The Journal of Head & Face Pain. 2007;47(1):73-80. 

Rozen T, Oshinsky M, Gebeline C, et al. Open label trial of coenzyme Q10 as a migraine preventive. Cephalalgia. 2002;22(2):137-141. 

Sándor PS, Di Clemente L, Coppola G, et al. Efficacy of coenzyme Q10 in migraine prophylaxis: a randomized controlled trial. Neurology. 2005;64(4):713-715.