CoQ10 Levels Reduced In Septic Shock

The first report on the levels of CoQ10 in human subjects with septic shock was published online on August 9, 2011 in the journal Critical Care. Sepsis is an inflammatory state resulting from the spread of infectious agents in the bloodstream. Sepsis and septic shock are a major cause of illness and mortality in the USA, with over 215,000 deaths occurring each year. The finding in this study that CoQ10 is low in sepsis opens the possibility for potential therapeutic intervention as CoQ10 can be administered exogenously. 

 

Michael W Donnino, Michael N Cocchi, Justin D Salciccioli, Daniel Kim, Ali Naini, Catherine Buettner and Praveen Akuthota
Coenzyme Q10 levels are low and are associated with the inflammatory cascade in septic shock
Critical Care 2011; 15 (4): R189. [Epub ahead of print]


ABSTRACT

Introduction:
Mitochondrial dysfunction is associated with increased mortality in septic shock. Coenzyme Q10 (CoQ10) is a key cofactor in the mitochondrial respiratory chain but whether CoQ10 is depleted in septic shock remains unknown. Moreover, statin therapy may decrease CoQ10 levels but whether this occurs acutely remains unknown. We measured CoQ10 levels in septic shock patients enrolled in a randomized trial of simvastatin versus placebo.

Methods:
Post-hoc analysis of a prospective randomized trial of simvastatin versus placebo in patients with septic shock (ClinicalTrials.gov ID: NCT00676897). Adult patients with suspected or confirmed infection and the need for vasopressor support were included in the initial trial. For the current analysis, blood specimens were analyzed for plasma CoQ10 and low-density lipoprotein levels. The relationship between CoQ10 levels and inflammatory and vascular endothelial biomarkers was assessed using Pearson or Spearman correlations.

Results:
28 samples from 14 patients were analyzed. CoQ10 levels were low with a median of 0.49 (IQR: 0.26 – 0.62) as compared to healthy control patients (CoQ10 = 0.95 umol/L +/- 0.29; p < 0.0001). Statin therapy had no effect on plasma CoQ10 levels over time (p = 0.13). There was a statistically significant relationship between CoQ10 level and vascular cell adhesion molecule (VCAM) (r2 = 0.2; p = 0.008), tumour necrosis factor- (r2 = 0.28; p=0.004), interleukin (IL)-8 (r2 = 0.21; p= 0.015), IL-10 (r2= 0.18; p=0.025), E-selectin (r2= 0.17; p=-0.03), IL-1ra (r2 =0.21; p=0.014), IL-6 (r2=0.17; p=0.029), and IL-2 (r2=0.23; p=0.009). Adjusting for low-density lipoprotein (LDL) levels there was a statistically significant inverse relationship between CoQ10 and VCAM (r2 = 0.24; p = 0.01; Figure 3) and IL-10 (r2 = 0.24; p = 0.02).

Conclusions:
CoQ10 levels are significantly lower in patients with septic shock compared to healthy controls. CoQ10 is negatively associated with vascular endothelial markers and inflammatory molecules though this association diminishes when adjusting for LDL levels.

The complete article is available as a provisional PDF.

 

 

Vitamin C: A Potential Life-saving Treatment For Sepsis

Physicians caring for patients with sepsis may soon have a new safe and cost-effective treatment for this life-threatening illness. Research led by Dr. Karel Tyml and his colleagues at The University of Western Ontario and Lawson Health Research Institute have found that vitamin C can not only prevent the onset of sepsis, but can reverse the disease.

Sepsis is caused by a bacterial infection that can begin anywhere in your body. Your immune system goes into overdrive, overwhelming normal processes in your blood. The result is that small blood clots form, blocking blood flow to vital organs. This can lead to organ failure. Babies, the elderly and those with weakened immune systems are most likely to get sepsis. But even healthy people can become deathly ill from the disease.

According to Dr. Tyml, a professor at Western’s Schulich School of Medicine & Dentistry, patients with severe sepsis have a high mortality rate, nearly 40 percent, because there is no effective treatment.

“There are many facets to sepsis, but the one we have focused on for the past 10 years is the plugging of capillaries,” says Dr. Tyml. Plugged capillaries prevent oxygenation and the supply of life-supporting materials to your organ tissue and stop the removal of metabolic waste product. Plugged capillaries are seen in organs of septic patients. These organs may eventually fail, leading to multiple organ failure and death. Dr. Tyml’s lab was the first to discover this plugging by using intravital microscopy, a technique Dr. Tyml pioneered in Canada.

According to Dr. Tyml’s most recent publication, oxidative stress and the activated blood clotting pathway are the major factors responsible for the capillary plugging in sepsis. Through his research, Dr. Tyml has discovered that a single bolus of vitamin C injected early at the time of induction of sepsis, prevents capillary plugging. He has also found that a delayed bolus injection of vitamin C can reverse plugging by restoring blood flow in previously plugged capillaries.

“Our research in mice with sepsis has found that early as well as delayed injections of vitamin C improves chance of survival significantly,” explains Dr. Tyml. “Furthermore, the beneficial effect of a single bolus injection of vitamin C is long lasting and prevents capillary plugging for up to 24 hours post-injection.”

Dr. Tyml and his colleagues are eager to find appropriate support to move this research from the bench to the bedside to see if these findings translate to patients with sepsis.

The potential benefit of this treatment is substantial. “Vitamin C is cheap and safe. Previous studies have shown that it can be injected intravenously into patients with no side effects,” says Dr. Tyml. “It has the potential to significantly improve the outcome of sepsis patients world-wide. This could be especially beneficially in developing countries where sepsis is more common and expensive treatments are not affordable.”
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