Coenzyme Q10 in sepsis patients

Relation

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

Study objective

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

Draft

Prospective, randomized study

Participant

Investigators examined consecutive patients admitted to the intensive care unit of a university 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 study, which included 31 men and 9 women. The mean age of the intervention group was 47.8 ± 22 years, while the mean age of the control group was 55.6 ± 19.4 years. Baseline inflammatory and oxidative markers between groups were not significantly different.

Inclusion criteria were:

• Alter ≥18 Jahre
• Vorliegen von 2 oder mehr der 4 Kriterien des systemischen Entzündungsreaktionssyndroms (SIRS):

1. Herzfrequenz >90 Schläge/Min
2. Atemfrequenz >20 Atemzüge/min oder Kohlendioxidpartialdruck (PaCO₂) < 32 mmHg
3. Verdacht auf oder bestätigte Infektion: weiße Blutkörperchen (WBC) > 12.000 Zellen/mm³oder < 4.000 Zellen/mm³oder > 10 % unreife (Banden-)Zellen
4. APACHE (Acute Physiologic Assessment and Chronic Health Evaluation) II erzielt bei der Aufnahme mehr als 15 Punkte. Der APACHE II-Score ist eine Berechnung von Labor- und klinischen Befunden zur Schätzung der Sterblichkeit auf der Intensivstation.¹

Exclusion criteria were:

• Koagulopathie, definiert als INR (international normalized ratio) >2
• Aktuelle Verwendung von Coenzym Q10 oder anderen Antioxidantien

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

Study parameters assessed

Participants received either 100 mg of coenzyme Q10 (ubiquinone) and standard sepsis care or standard sepsis care alone twice daily for 7 days. Standard care for sepsis includes early resuscitation within the first 6 hours of admission, diagnostic tests to identify the causative organisms, and broad-spectrum antibiotic therapy followed by microbiological testing.

Primary outcome measures

Primary endpoints were changes in inflammation as measured by interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) concentrations. Primary endpoints also included oxidative damage as assessed by malondialdehyde (MDA) and glutathione peroxidase. The researchers measured these markers at baseline, day 3, and 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 procedure lasted only 7 days, patients remained in the hospital until they were satisfactorily discharged or until they died. Therefore, secondary outcomes included length 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 insights

Two of the 4 inflammatory markers showed improvements.

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

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

Secondary endpoints: Coenzyme Q10 did not change SOFA or SAPS-II scores during the 7-day study period. The length of stay in the intensive care unit did not differ significantly between the two groups.

Practice implications

This study provides a modest intervention with modest results for a population that at first glance does not appear to be entirely relevant to outpatient clinical practice. Regardless of these characteristics, there may be some nuanced takeaways for those engaged in naturopathic practice.

Coenzyme Q10 is often used in neurological cases with the understanding that it can support mitochondrial function and in turn improve clinical outcomes, especially when a deficiency is identified or suspected. This study brings further awareness to the role of mitochondrial function in immunocompromised individuals, another population potentially prone to CoQ10 deficiency.^2-4

Treatment of patients with sepsis often focuses on macrocirculatory resuscitation through treatment with fluids and/or blood transfusions and/or inotropes.⁵Unfortunately, in all cases it is not enough to achieve blood flow to the tissue. Cells must be able to utilize energy substrates to properly form adenosine triphosphate (ATP). If this is not the case, cytopenic hypoxia can result and partial or complete organ failure can result. CoQ10 is known to play an essential role in the electron transport chain. In particular, it serves as a carrier of electrons from complexes I and II to complex III. Cellular respiration in the mitochondria can be impaired when this mechanism is disrupted, resulting in reduced intracellular ATP production.

One feature of this study that may be noticeable to practitioners is the fairly low dose of CoQ10 used in these sick patients; 200 mg of CoQ10 may be a common, typical daily dose, although not on the low side, used in outpatient care. Treatment of mitochondrial myopathies can begin with dosages of 400 mg per day.⁶In the Q-SYMBIO study, 420 patients with chronic heart failure of NYHA (New York Heart Association) functional class III or IV received 300 mg of CoQ10 daily plus standard therapy in the active group.⁷Other clinical studies have used much higher doses of CoQ10 in various patient populations, including 1,200 mg and 2,400 mg in patients with Parkinson's disease⁸and up to 3,000 mg in patients with amyotrophic lateral sclerosis (ALS).⁹

Second, the description of Coenzyme Q10 in the paper suggests the use of ubiquinone compared to the reduced form of ubiquinol, which might also catch the eye of a practitioner. This feature is particularly interesting because a previous pilot study used ubiquinol 200 mg twice daily in a similar patient population.¹⁰Ubiquinol is thought to increase plasma levels of ubiquinone better than ubiquinone itself.¹¹The lead author confirmed that ubiquinone was used in this study and administration (oral or nasogastric tube) depended on the patient's ability.

Systemic infections, such as those present in the population studied, often require heroic interventions, as implied by the ICU admission in this study. However, the practice implications relevant to out-of-hospital care may be the use of CoQ10 in those patients most at risk of sepsis complications. The Centers for Disease Control and Prevention highlights a few patient populations at greatest risk, including those age 65 and 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.¹²Considering mitochondria as a target for intervention in the early treatment of sepsis and potentially preventing immune system dysregulation is an attractive finding from a study like this. Considering that the dosage range of oral administration is wide, higher dosages may be required to achieve the intended clinical results. Future studies will undoubtedly expand our understanding of the use of CoQ10 and other nutrients to support mitochondria in immune-dependent diseases such as sepsis.

Disclosure of Conflicts of Interest

The author is an employee of Integrative Therapeutics, which profits from sales of Coenzyme Q10 products.