Coenzyme Q10 (CoQ10) is the only lipid-soluble antioxidant produced by the body and plays both a direct and indirect role in protecting cells against oxidative damage. Not only does CoQ10 prevent the generation of free radicals and therefore the oxidative modification of proteins, lipids, and DNA, but it also regenerates other antioxidants including alpha lipoic acid and vitamins C and E. The amount of endogenously produced CoQ10 diminishes naturally as we age (our capacity to make CoQ10 appears to peak around the age of 25); levels are also reduced as a consequence of extreme exercise and is depleted in a number of health conditions, and by a number of pharmaceuticals. The fundamental consequence of low CoQ10, in addition to poor energy production, is an increased vulnerability to oxidative stress-induced cell damage. Nutritional intervention to raise levels in an individual at risk from low CoQ10 – or increased need of – is therefore necessary to prevent the negative impact this could have.
Mitochondria and the electron transport chain
CoQ10 is a vital component in the production of ATP (adenosine triphosphate), our energy currency, required to carry out all physiological and metabolic processes. ATP is made by the mitochondria, via a series of 5 protein complexes (the electron transport chain) embedded in the highly folded ‘cristae’ of folds of the inner membrane of the mitochondria. Electrons, produced from the reduction of ubiquinone to ubiquinol, are passed between the first three complexes in the chain, with the 5th complex responsible for the final step of the ATP production and so the levels of CoQ10 available to the mitochondria directly affect the efficiency of energy generation. Disruption of the process compromises oxidative phosphorylation, leading to decreased levels of cellular ATP production. Mitochondrial dysfunction and high oxidative cell damage is a key feature in the onset and progression of neurodegenerative diseases. As a result, there is significant interest in exploring the use of CoQ10 for the potential treatment of neurodegenerative disorders, which appears to be an increasingly promising neuroprotectant to slow progression of Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and other neurodegenerative disorders.
Major hallmarks in the pathophysiology of Parkinson’s disease are cellular energy depletion and oxidative stress, leading to cellular dysfunction and death. The neurotoxin precursor N-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) is, for example, used in animal models to induce Parkinsonism through the inhibition of the first complex of the mitochondrial electron transporter chain which leads to a loss of both dopamine and dopaminergic axons, which can subsequently be rectified upon CoQ10 supplementation.  Thus the recognition that MPTP can induce a Parkinsonian syndrome by inhibiting mitochondrial complex I activity supports the role of mitochondrial dysfunction in Parkinson’s disease onset and subsequent studies have observed significantly lower levels of CoQ10 in the mitochondria of Parkinson’s patients when compared to age and sex-matched controls. In addition, a decrease in complex I activity in studies of patients with Parkinson’s disease has also been demonstrated. 
Parkinson’s is a progressive disease; established drug treatments can help slow, but not halt disease progress and often come with side effects. In 2002, a small study published findings suggesting that taking 1,200 mg/day of CoQ10 (as oxidised ubiquinone) may benefit those with early Parkinson’s disease. This randomised placebo-controlled, double-blind trial enrolled eighty subjects with early Parkinson’s disease (who did not require treatment for their disability) and randomly assigned them to receive placebo or coenzyme CoQ10 at doses of 300, 600, or 1200 mg/d. Less disability developed in subjects assigned to CoQ10 than in those assigned to placebo, and the benefit was greatest in subjects receiving the highest dose.  This study gathered much excitement, resulting in a follow-on phase III trial that recruited more than 600 participants who were randomly assigned to receive placebo or CoQ10 at doses 1200 mg/d or 2400 mg/d. The trial was, however, stopped early because although CoQ10 levels increased, there was some worsening of symptom severity reported in the CoQ10 groups compared to placebo as determined by the Unified Parkinson’s Disease Rating Scale (UPDRS).  The findings of this latter study were finally published in 2014 with two additional, relatively small studies published in the interim also failing to report any significant benefit from ubiquinone intervention in early Parkinson’s disease. [5,6] It would be reasonable to assume at this point that CoQ10 intervention offers little or no benefit for those suffering with early Parkinson’s – until we consider that these trials all used the oxidized ubiquinone form of CoQ10. In contrast, more recent evidence suggests that the reduced, ubiquinol form of CoQ10 may, unlike ubiquinone, offer benefits for Parkinson’s patients.
Ubiquinol, the electron-rich (reduced) form of CoQ10, wasn’t available in supplements until 2006. It is not only more absorbable than conventional CoQ10 (ubiquinone) but also exhibits better neuroprotective effects than the ubiquinone form: 200 mg/kg/day of ubiquinol has been demonstrated to be more effective in an MPTP-induced mouse model of Parkinson’s disease than the same dose of the oxidised form of CoQ10. Thus, the most recent study published in 2015 may offer hope for Parkinson interventions. Indeed, in this randomised, double-blind, placebo-controlled pilot trial, participants were recruited to receive 300 mg/day of ubiquinol (rather than ubiquinone) or placebo for 48 weeks or 96 weeks. Participants were divided into two groups: Parkinson’s disease experiencing wearing off (a situation where levodopa no longer seems to work as effectively as it used to – (Group A)), and early Parkinson’s disease, without levodopa (Group B). Participants took 300 mg of ubiquinol or placebo per day for 48 weeks (Group A) or 96 weeks (Group B). Supplementation with ubiquinol increased plasma levels of total CoQ10 as much as ten times compared to baseline, while placebo treatment did not. Interestingly, the UPDRS scores decreased in the ubiquinol group of individuals with Parkinson’s disease experiencing wearing off but not in the group with early Parkinson’s not receiving treatment with levodopa, indicating that ubiquinol may be effective in treating Parkinson’s disease, perhaps by reversing mitochondrial abnormalities characteristic of Parkinson’s disease, but less so for preventing the progress of the condition. The number of subjects in this Phase II trial were small, however, and a larger clinical study will be needed to support this early data.
CoQ10 and dementia
CoQ10, along with a number of other nutrients, micronutrients and metabolic enzymes known to be essential for substrate metabolism, substrate utilisation and energy transfer are known to reduce with age. A reduction in the body’s natural antioxidant defence system renders cells susceptible to oxidative mitochondrial decay, which is a major contributor to both ageing and neural degeneration. Indeed, the oxidants generated by mitochondria appear to be the major source of the oxidative lesions that accumulate with age and may predispose an individual to cognitive decline and/or dementia. One of the neuropathological features of Alzheimer’s disease is, for example, the deposition of senile plaques containing beta-amyloid (β-amyloid). The antioxidant ability of CoQ10 to reduce intracellular deposition of b-amyloid in rodent studies [9,10] has exciting potential for Alzheimer’s disease, which involves a chronic inflammatory response associated with both brain ‘insult’ as well as β-amyloid associated pathology. For example, β-amyloid inhibits the proliferation of neural stem cells working via phosphatidylinositol 3-kinase (PI3K). This pathway modulates neuronal cell survival in Alzheimer’s disease, and animal models show that CoQ10 functions to restore amyloid β-inhibited proliferation of neural stem cells by activating the PI3K pathway. In addition, not only does CoQ10 treatment result in decreased levels of amyloid-β protein precursor (AβPP), decreased plaque area and numbers, but CoQ10-treated mice also show improved cognitive performance. Whilst experimental studies have shown the neuroprotective effects of CoQ10, the expansion of such findings in human studies is, however, still limited: a 2012 randomized clinical trial with 400 mg CoQ10 three times/day for 16 weeks in 78 patients with mild to moderate Alzheimer’s disease resulted in higher CoQ10 levels but did not show any significant beneficial effects on biomarkers for Alzheimer’s disease, including β-amyloid. Yet CoQ10 levels in individuals with dementia are clearly lower than individuals without dementia. In platelets obtained from patients with Alzheimer’s disease, complex I activity has been found to be increased, complex IV activity decreased, and plasma concentrations of CoQ10 also decreased. A recent (2014) study showed an inverse association between serum CoQ10 levels and disabling dementia, implying that increasing serum CoQ10 levels may have a beneficial effect on prevention of dementia. The lack of observed benefits in human studies of CoQ10 intervention in dementia may be similar to that of Parkinson’s studies using ubiquinone; more studies utilising ubiquinol are needed to clarify the true potential of CoQ10 in dementia.
Take home message
Oxidative mitochondrial decay or mitochondrial dysfunction with abnormal energy metabolism are both major contributors to neural degeneration; the oxidants generated by mitochondria appear to be the major source of the oxidative lesions that accumulate with age and may predispose an individual to neurodegenerative conditions. CoQ10 levels are directly correlated with increasing age and low levels observed in a number of neurodegenerative conditions. Animal studies support the use of CoQ10 as a modifier of the impact of oxidative stress but what appears increasingly clear is that simply raising levels of CoQ10 (as ubiquinone) in humans doesn’t necessarily result in positive clinical outcomes, whereas they have been reported in trials using the reduced form – ubiquinol. Since ubiquinol is an antioxidant and is required for ATP production, practitioners need to be aware of the potential role of this supplement over standard CoQ10 products.
VESIsorb® Ubiquinol-QH from Igennus Healthcare Nutrition is the most advanced CoQ10 supplement available in the UK. VESIsorb® is a clever delivery system which mimics the natural transport system of the intestine using a patented colloidal technology that converts ubiquinol into a water-soluble nutrient, in effect pre-digesting it into tiny water-soluble particles that pass easily through the unstirred water layer barrier into the gut cells where it is fast-tracked into the bloodstream. VESIsorb® has been shown to raise CoQ10 levels to double the levels required to have a therapeutic impact, acting twice as fast and lasting up to six times longer than the same dose of a product without VESIsorb® delivery.
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