Coenzyme Q10 in Sepsis Patients

Results from a prospective, randomized trial

By Corey B. Schuler, RN, MS, CNS, CNSC, DC

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Reference

Soltani R, Alikiaie B, Shafiee F, Amiri H, Mousavi S. Coenzyme Q10 improves the survival and reduces inflammatory markers in septic patients. Bratisl Lek Listy. 2020;121(2):154-158.

Study Objective

To assess the effect of coenzyme Q10 (CoQ10) on markers of inflammation, organ failure assessment, duration of intensive care unit (ICU) stay, and in-hospital mortality for patients in the early phase of sepsis receiving routine care plus CoQ10 compared to patients receiving only routine care

Design

Prospective, randomized trial

Participants

Investigators screened consecutive patients admitted to the ICU of a university-affiliated hospital in Isfahan, Iran, and randomly assigned 57 patients to either the control group (n=28) or the intervention group (n=29). Forty (N=40) patients (20 in each arm) completed the trial, which comprised 31 men and 9 women. Median age of the intervention group was 47.8±22 years, while the median age of the control group was 55.6±19.4 years. Baseline inflammatory and oxidative markers between the groups were not significantly different.

Inclusion criteria included:

  • Age ≥18 years
  • Having 2 or more of the 4 systemic inflammatory response syndrome (SIRS) criteria:
  1. Heart rate >90 beats/min
  2. Respiratory rate >20 breaths/min or partial pressure of carbon dioxide (PaCO2) <32 mmHg
  3. Suspected or confirmed infection: white blood cells (WBC) >12,000 cells/mm3, or <4,000 cells/mm3, or >10% immature (band) cells
  4. APACHE (Acute Physiologic Assessment and Chronic Health Evaluation) II score more than 15 at admission. APACHE II score is a calculation of laboratory and clinical findings to estimate ICU mortality.1

Exclusion criteria were:

  • Coagulopathy as defined as an INR (international normalized ratio) >2
  • Current use of CoQ10 or any other antioxidant

The trial also excluded patients who were unable to receive enteral medication, were pregnant, were currently participating in other studies, or had end-stage or do-not-resuscitate (DNR) orders.

Study Parameters Assessed

Participants received either 100 mg of CoQ10 (ubiquinone) twice daily for 7 days and standard care for sepsis or standard care for sepsis alone. Standard care for sepsis includes early resuscitation within the first 6 hours of admission, diagnostic studies to determine causative organisms, and broad-spectrum antibiotic therapy with follow-up microbiologic tests.

Primary Outcome Measures

Primary endpoints were changes in inflammation, as measured by levels of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α). Primary endpoints also included oxidative injury as determined by malondialdehyde (MDA) and glutathione peroxidase. Investigators measured these markers at baseline, on day 3, and on day 7 in both the intervention and control arms.

The in-hospital mortality rate was 20% for the CoQ10 group and 65% for the control group.

While the intervention was only for 7 days, patients remained hospitalized until they could be satisfactorily discharged or until death. Therefore, secondary outcome measures included duration of hospital stay and in-hospital mortality rate. Sequential Organ Failure Assessment (SOFA) score and Simplified Acute Physiology Score (SAPS II) were also secondary endpoints.

Key Findings

Two out of the 4 inflammatory markers showed improvements.

Decreases in TNF-α (P=0.003) and MDA (P=0.003) levels were seen on the 7th day in the group receiving CoQ10 when compared to the control group and to baseline.

IL-6 levels also were reduced versus baseline and between arms; however, this finding did not reach statistical significance (P=0.22). No change was seen in glutathione peroxidase over the 7-day study between the 2 groups. The in-hospital mortality rate was 20% for the CoQ10 group and 65% for the control group (P=0.01).

Secondary endpoints: CoQ10 did not change SOFA or SAPS II scores during the 7-day study period. Duration of ICU stay was not significantly different between the 2 groups.

Practice Implications

This study provides a modest intervention with modest results to a population that may not seem, at first glance, entirely relevant for ambulatory clinical practice. Notwithstanding those features, there may be some nuanced takeaways for those in natural medicine practice.

Coenzyme Q10 is often used in neurological cases with the understanding that it may support mitochondrial function and, in turn, improve clinical outcomes, especially when a deficiency is noted or suspected. This study brings further awareness to the role of mitochondrial function in immune-compromised individuals, another population that may have a tendency for CoQ10 deficiency.2-4

Managing patients with sepsis often focuses on macrocirculatory resuscitation through management with fluids and/or blood transfusion and/or inotropic agents.5 Unfortunately, getting circulation to tissues may not be sufficient in all cases. Cells must be able to utilize energy substrates to form adenosine triphosphate (ATP) properly. In the absence of this, cytopenic hypoxia may result, and partial or total organ failure can be the consequence. It is well known that CoQ10 plays an essential role in the electron transport chain. Specifically, it serves as the carrier of electrons from complexes I and II to complex III. Cellular respiration in the mitochondria can be compromised when this mechanism is disrupted, resulting in decreased intracellular ATP production.

One feature of this study that practitioners may notice is the rather low dose of CoQ10 used in these ill patients; 200 mg of CoQ10 may be a common, typical daily dose, if not on the low side, used in ambulatory care. Treatment of mitochondrial myopathies may begin at dosages of 400 mg per day.6 In the Q-SYMBIO trial, 420 patients with chronic NYHA (New York Heart Association) functional class III or IV heart failure received 300 mg of CoQ10 daily in the active group plus standard therapy.7 Other clinical trials have used much higher doses of CoQ10 in different patient populations, including 1,200 mg and 2,400 mg in patients with Parkinson's disease8 and up to 3,000 mg in patients with amyotrophic lateral sclerosis (ALS).9

Second, the description of CoQ10 in the publication suggests the use of ubiquinone versus the reduced-form ubiquinol, which may also catch a practitioner's eye. This feature is especially interesting since a previous pilot study used 200 mg of ubiquinol twice daily in a similar patient population.10 Ubiquinol is thought to elevate plasma levels of ubiquinone better than ubiquinone itself.11 The primary author confirmed ubiquinone was used in this study, and administration (oral or nasogastric gavage) depended on the patient's ability.

Systemic infections like the ones present in the population under study often require heroic interventions, as implied by admission to the ICU in this study. Yet, the practice implications relevant to nonhospital care may be the use of CoQ10 in those patients most at risk for sepsis complications. The Centers for Disease Control and Prevention highlight a few patient populations at greatest risk and includes those who are 65 years of age or older, those with chronic medical conditions, such as diabetes, lung disease, cancer, and kidney disease, those with weakened immune systems, and also those who have survived an episode of sepsis.12 Viewing mitochondria as a target of intervention in the early treatment of sepsis and potentially the prevention of immune dysregulation is an attractive takeaway from a study such as this. Also, reconsidering that the dosage range of oral administration is broad, higher dosages may be required to achieve intended clinical outcomes. Future trials will undoubtedly add detail to our understanding of the use of CoQ10 and other mitochondrial-support nutrients in immune-dependent conditions such as sepsis.

Conflict of Interest Disclosure

The author is employed by Integrative Therapeutics, which profits from the sale of coenzyme Q10 products.

About the Author

Corey B. Schuler, RN, MS, CNS, CNSC, DC, serves as director of clinical affairs for Integrative Therapeutics. He is a registered nurse and certified nutrition specialist and nutrition support clinician. He received his chiropractic doctorate from Northwestern Health Sciences University and his master of science in human nutrition from the University of Bridgeport, and is completing a family nurse practitioner program at Graceland University. He has additionally earned an executive master of business administration and an undergraduate degree in chemistry. Schuler authored a chapter in the textbook Integrative Medical Nutrition Therapy (Springer, 2020) and serves as an adjunct professor in nutrition and business programs. Schuler is based in Minnesota.

References

  1. APACHE II Score. MD Calc. https://www.mdcalc.com/apache-ii-score. Accessed November 12, 2020.
  2. Donnino MW, Cocchi MN, Salciccioli JD, et al. Coenzyme Q10 levels are low and may be associated with the inflammatory cascade in septic shock. Crit Care. 2011;15(4):R189.
  3. Dupic L, Huet O, Duranteau J. Coenzyme Q10 deficiency in septic shock patients. Crit Care. 2011;15(5):194.
  4. Coppadoro A, Berra L, Kumar A, et al. Critical illness is associated with decreased plasma levels of coenzyme Q10: a cross-sectional study. J Crit Care. 2013;28(5):571–576.
  5. Vincent JL. Current management of sepsis and septic shock. Signa Vitae. 2016;11(2):14-16.
  6. O'Ferrall E. Mitochondrial myopathies: treatment. UpToDate. https://www.uptodate.com/contents/mitochondrial-myopathies-treatment. Accessed November 12, 2020.
  7. Mortensen SA, Rosenfeldt F, Kumar A, et al. The effect of coenzyme Q10 on morbidity and mortality in chronic heart failure: results from Q-SYMBIO: a randomized double-blind trial. JACC Heart Fail. 2014;2(6):641-649.
  8. Parkinson Study Group QE3 Investigators, Beal MF, Oakes D, et al. A randomized clinical trial of high-dosage coenzyme Q10 in early Parkinson disease: no evidence of benefit. JAMA Neurol. 2014;71(5):543-552.
  9. Ferrante KL, Shefner J, Zhang H, et al. Tolerance of high-dose (3,000 mg/day) coenzyme Q10 in ALS. Neurology. 2005;65(11):1834-1836. 7
  10. Donnino MW, Mortensen SJ, Andersen LW, et al. Ubiquinol (reduced coenzyme Q10) in patients with severe sepsis or septic shock: a randomized, double-blind, placebo-controlled, pilot trial. Crit Care. 2015;19(1):275.
  11. Zhang Y, Liu J, Chen XQ, Oliver Chen CY. Ubiquinol is superior to ubiquinone to enhance coenzyme Q10 status in older men. Food Funct. 2018;9(11):5653-5659.
  12. Centers for Disease Control and Prevention. What is sepsis? Centers for Disease Control and Prevention. https://www.cdc.gov/sepsis/what-is-sepsis.html. Accessed November 12, 2020.