Sid Shastri, MSc07.26.10
CoQ10 has become one of the most important nutrients in the nutrition industry, far beyond its original role as an esoteric, "specialty" antioxidant. The mitochondrial star used to be only a single-entity product, but it is now an anchor ingredient in a variety of formulations ranging from sports nutrition to cognitive health.
Recently, the CoQ10 community marked a special moment as it celebrated the 6th International Coenzyme Q10 Association symposium (May 27th-30th, 2010), held in Brussels, Belgium. This biennial event is a rare opportunity to learn from researchers around the world on the latest breakthroughs in CoQ10, including topics related to mitochondrial bioenergetics, metabolic, and neurological aspects.
Parkinsonism & Huntington’s disease
One of the highlights of the symposium was a presentation by neuroscientist Dr. Flint Beal, Department of Neurology and Neuroscience at Weill Medical College of Cornell University. His research includes authoring or co-authoring more than 300 scientific articles, as well as serving on the editorial board of seven journals. Dr. Beal presented some of his group’s most recent findings on mitochondrial dysfunction and neurodegenerative diseases, specifically involving animal models of Parkinson’s and Huntington’s disease to compare ubiquinol and conventional CoQ10.
In one of the animal models, they utilized a neurotoxin called MPTP, which induces effects in the brain that are analogous to clinical and biochemical changes seen in patients with Parkinson’s disease. Administration of the MPTP caused the formation of alpha synuclein aggregates, which are a major pathological hallmark found in Parkinson’s disease. The rodents treated with CoQ10 (both ubiquinone—the oxidized form of CoQ10—and ubiquinol forms) had significantly less formation of these aggregates. Additionally, the scientists noted that the ubiquinol form resulted in higher plasma levels and exerted a greater neuroprotective effect against the damaging effect of MPTP.
Another nutrient that Dr Beal’s group investigated was creatine, the naturally-occurring alpha amino acid derivative. In the form of phosphocreatine, it can be an ATP (energy) buffer that can be critical for tissues with high energy requirements like the brain and muscle. Utilizing mouse models of Parkinson’s disease (MPTP) and Huntington’s disease (3-NP and transgenic model), the scientists tested CoQ10 and creatine, separately and in combination. The research revealed that the combination of CoQ10 and creatine (ratio of 1:2) exerted additive neuroprotective effects against both MPTP, 3-NP, and transgenic models of neurodegeneration. While CoQ10 and creatine are involved in different energetic pathways, the experimental research indicates a promising possibility for future studies of the combination.
CoQ10 & Heart Dysfunction
Cardiologists eagerly anticipated the lecture from Dr. Peter Langsjoen, based in Texas. He discussed his experiences during the last four years with ubiquinol and patients at his clinic. An initial group of subjects with end stage congestive heart failure (NYHA Class IV) were being given an average of 450 mg per day of ubiquinone. Despite the supplemental ubiquinone, blood values were a mean of 1.6 mcg/mL plasma. Distilling decades of experience in cardiology, Dr. Langsjoen pointed out that the blood values necessary for a beneficial effect continue to be recalibrated higher. In 1980, the therapeutic value was thought to require x>1.0 mcg/mL CoQ10 of plasma. By 1990, that value was 2.5 mcg/mL of plasma. Their most recent work indicates that blood values in excess of 3.5 mcg/mL of plasma are sought for therapeutic effect.
In the hopes of improving their cardiovascular health, these Class IV CHF patients were then switched over to the ubiquinol form. The results showed a dramatic increase in bioavailability, achieving desired therapeutic plasma values only with the ubiquinol. Based on the initial data, Dr. Langsjoen expanded the number of patients on ubiquinol. And for a variety of markers associated with cardiovascular function, ranging from plasma CoQ10 levels to ejection fraction, the ubiquinol showed better benefit with less amounts required. For instance, ejection fractions were at more than 41% for ubiquinone and 48% for ubiquinol; NYHA Class on ubiquinol was 1.6, while subjects on ubiquinone were at 2.5. As these positive effects were observed, they have administered the ubiquinol to approximately another 300 patients. In the future, work by Dr. Langsjoen will look at 200 mg of ubiquinol twice daily with meals, with exclusion of greater than 300 IUs per day of vitamin E (as tocopherol may antagonize absorption).
Tales of Tails & Genes
Often, the CoQ10 molecule is described as having a polar region (benzoquinone or benzoquinol) and a flat, non-polar/hydrophobic region called the “tail.” The tail is a decaprenylated side chain, and in mammals only CoQ9 and CoQ10 are found (the former only in rodents). One of the poster presentations by a group of scientists led by University of Granada (Spain) evaluated the effects of CoQ10, CoQ2 and idebenone (which has a 10 carbon side chain as opposed to a 50 carbon chain for CoQ10) in oxidative stress and energetics. This novel in vitro experiment was conducted on fibroblast cells from patients that were known to have a primary CoQ10 deficiency, which is a pathogenic mutation on any of the CoQ genes. Other patients with mitochondrial genetic mutations independent of the CoQ biosynthesis pathway are considered a secondary deficiency.
Looking at this model is relevant, as researchers have noted an increase in the number of patients with mitochondrial disorders showing a deficiency of CoQ. The scientists determined that the short tailed version of CoQ10 (CoQ2) and idebenone were not able to replace the function of CoQ10 in the mitochondrial respiratory chain. In other words, the tail is not simply an appendage but rather an indispensable component of the CoQ10 molecule.
Genetics Research & CoQ10
The increasing sophistication of our understanding of CoQ10 can be seen from the works of Dr. Schmelzer and her team of researchers at the University of Kiel in Germany. These molecular scientists have published numerous studies investigating the effects of CoQ10 (both ubiquinone and ubiquinol) on gene expression in many different in vitro (murine and human cells) and in vivo models.
Of the series of studies they’ve published, one of their original publications showed CoQ10 exerted an anti-inflammatory presence against a known inflammatory agent called lipopolysaccharide. Further research from the group involved an in vivo experiment (SAMP1, an accelerated aging rodent model) where they detected the presence of redox-sensitive genes, specifically ubiquinol-dependent gene networks that are involved in inflammation and lipid metabolism. In the same study, the research also indicated that, in comparison to ubiquinone, ubiquinol supplementation was more effective at increasing total CoQ10 levels in the liver.
At the conference, the German researchers presented their latest findings of a clinical investigation involving 53 subjects administered 150 mg ubiquinol per day. Isolated monocytes were sampled from the subjects to conduct stringent microarray review. It was learned that there are ubiquinol-dependent genes in the NFkB (a pivotal pro-inflammatory protein complex) and PPAR-α signaling pathways (PPAR-α is strongly involved in lipid metabolism), again providing evidence that ubiquinol reduces the inflammatory process. Metabolically, the 150 mg per ubiquinol per day was able to show significant reduction effects on serum LDL Cholesterol.
New Faces & The Future
Only at a conference like this might you learn of things like genetic mutation causing CoQ10 deficiencies or the structural importance of the CoQ10 tail. The CoQ10 universe continues to expand, and I met with many new scientists—some of whom are just beginning to serve years, if not decades, for this association. But one member in particular provided the leadership for the conference: Dr Gian Paolo Littarru, from Marche Polytechnic University (Ancona, Italy). Dr Littarru’s research in CoQ10 spans more than 40 years and his efforts were central to the success of this symposium.
About the author: Sid Shastri is the product development manager for Kaneka Nutrients. He holds a degree in human biodynamics from the University of California Berkeley. In 2004, Mr. Shastri earned his master’s of science degree in human nutrition from the University of Bridgeport.
