Tolerance of high-dose (3,000 mg/day) coenzyme Q10 in ALS

Ferrante, Kimberly L.; Shefner, Jeremy M.; Zhang, H.; Betensky, Rebecca A.; O'Brien, Margaret; Yu, Haijing; Fantasia, M. A.; Taft, J; Beal, M. Flint; Traynor, Bryan J.; Newhall, Kristyn; Donofrio, Peter D.; Caress, James B.; Ashburn, C.; Freiberg, Barbara Loggan; OʼNeill, Christine; Paladenech, Connie; Walker, Tracey; Pestronk, Alan; Abrams, Berenice; Florence, J.; Renna, Renee; Schierbecker, Jeanine; Malkus, Betsy; Cudkowicz, Merit

doi:10.1212/01.wnl.0000187070.35365.d7

Cited by 143 publications

(85 citation statements)

References 8 publications

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“…Treatment for conditions such as hypercholesterolemia, congestive heart failure, mitochondrial disorders, statin-induced CoQ depletion, and for enhancing exercise tolerance have used dosage similar to the low dose supplemented in the current study (Beal 1999;Rosenfeldt et al 2003Rosenfeldt et al , 2007Marcoff and Thompson 2007 ), whereas the high-CoQ dose can be related to doses used in clinical trials for the treatment of Parkinson's disease (Shults and Haas 2005) or Alzheimer's disease (trial NCT00117403), and doses up to 3,000 mg/day have been examined for short periods and determined to be void of toxic effects (Ferrante et al 2005). The highCoQ dose used in our study was beneficial for spatial learning and memory when used for a short period of time; when used lifelong, a similar dose led to significant deleterious effects (Sumien et al 2009).…”

Section: Discussionmentioning

confidence: 99%

Coenzyme Q10 supplementation reverses age-related impairments in spatial learning and lowers protein oxidation

Shetty

Forster

Sumien

2012

AGE

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Coenzyme Q10 (CoQ) is widely available as a dietary supplement and remains under consideration as a treatment for age-associated neurodegenerative conditions. However, no studies have determined if supplementation, initiated relatively late in life, could have beneficial effects on mild functional impairments associated with normal brain aging. Accordingly, the current study assessed the effect of CoQ intake in older mice for which cognitive and psychomotor impairments were already evident. Separate groups of young (3.5 months) and relatively old mice (17.5 months) were fed a control diet or a diet supplemented with low (0.72 mg/g) or high (2.81 mg/g) concentrations of CoQ for 15 weeks. After 6 weeks, the mice were given tests for spatial learning (Morris water maze), spontaneous locomotor activity, motor coordination, and startle reflex. Age-related impairments in cognitive and psychomotor functions were evident in the 17.5-month-old mice fed the control diet, and the low-CoQ diet failed to affect any aspect of the impaired performance. However, in the Morris water maze test, old mice on the high-CoQ diet swam to the safe platform with greater efficiency than the mice on the control diet. The old mice supplemented with the highCoQ diet did not show improvement when spatial performance was measured using probe trials and failed to show improvement in other tests of behavioral performance. Protein oxidative damage was decreased in the mitochondria from the heart, liver, and skeletal muscle of the high-CoQ-supplemented mice and, to some extent, in the brain mitochondria. Contrasting with the deleterious effect of long-term CoQ supplementation initiated during young adulthood previously published, this study suggests that CoQ improves spatial learning and attenuates oxidative damage when administered in relatively high doses and delayed until early senescence, after agerelated declines have occurred. Thus, in individuals with age-associated symptoms of cognitive decline, highCoQ intake may be beneficial.

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Section: Discussionmentioning

confidence: 99%

Coenzyme Q10 supplementation reverses age-related impairments in spatial learning and lowers protein oxidation

Shetty

Forster

Sumien

2012

AGE

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“…Coenzyme Q10, a cofactor in the electron transfer chain, is also a scavenger of free radicals in lipid and mitochondrial membranes, and is thought to improve energy production by the mitochondrial membrane and the cell. Although the administration of high doses (up to 3,000 mg) of CoQ10 plus vitamin E (1,500 mg) to ALS patients was found to be generally safe, no clinical benefit was detected (41). Edaravone, a potent scavenger of free radicals that is approved in Japan for the treatment of ALS, was tested in 20 Japanese patients in a small double-blind study (145).…”

Section: Therapeutic Approaches To Alsmentioning

confidence: 99%

Redox Modifier Genes and Pathways in Amyotrophic Lateral Sclerosis

Carter

Anklesaria

Choi

et al. 2009

Antioxidants & Redox Signaling

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Enhanced redox-stress caused by neuroinflammation, mitochondria, and NADPH oxidases has been hypothesized to play critical roles in disease progression of amyotrophic lateral sclerosis (ALS). However, distinguishing whether the redox-stress observed in ALS is due to a primary defect in cellular reactive oxygen species metabolism=catabolism, or is a secondary consequence of neuroinflammation, has been difficult and the issue remains a matter of debate. Emerging evidence suggests that defects in genes that regulate NADPH oxidases may account for at least some forms of ALS. NADPH oxidases are key signaling complexes that influence cellular responses to growth factors and cytokines. In this context, NADPH oxidase-derived reactive oxygen species exert spatial control over the redox-dependent activation of certain pro-inflammatory receptors. Understanding the biology of how NADPH oxidases control cell signaling may help to clarify how genetic determinants of ALS lead to dysregulated pro-inflammatory signaling. This review provides a framework for understanding endosomal signaling through NADPH oxidases and potential mechanisms whereby gene defects in various forms of ALS may influence this cellular process and lead to motor neuron degeneration. Lastly, this review discusses past and current efforts to treat ALS using antioxidant therapies, as well as the limitations and advantages of each of these approaches. Antioxid. Redox Signal. 11, 1569-1586.

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“…Reported adverse gastrointestinal effects: nausea, upset stomach and vomiting, during clinical trials showed that, because no dose-response relationship was defined, the gastrointestinal effects are not related with the active ingredient [8,9]. 1,200 mgCoq10 taken daily produces no adverse side effects and levels as high as 3,000 mg/day were tested without adverse effects; although at this level there is no adequate product safety information [9][10][11]. Taken orally, Coq10 in a crystalline form is poorly absorbed.…”

Section: Pharmacokinetic Parameters Of Coq10mentioning

confidence: 99%

The Role of Coenzyme Q10 Supplementation with Statin Drug Use and Chronic Diseases

Peres¹,

Foss²,

Pereira³

2017

J Infect Dis Preve Med

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Patients with chronic diseases exhibit a deficiency of Coenzyme Q10 (Coq10). Also, there is no doubt lowering cholesterol medication, statin drugs will "reduce the natural levels of CoQ10 in the body" Known to have antioxidant effects, Coq10 is essential for the proper functioning of adenine triphosphate (ATP) energy production in the cells. There is medical literature with positive recommendations for Coq10 supplementation with statin drugs. Unfortunately, because of controversial studies cited in the literature, there exists misinformation about the benefits of Coq10 supplementation in patients taking statins. Thus, the objective this mini-review is to discuss the beneficial role Coq10 supplementation provided to individuals taking statins and to encouraging doctors and health professionals to prescribe Coq10. Some of the negative feedback stems from the low bioavailability of oral Coq10 supplements. However, newer sublingual Coq10 supplementation formulas are much more absorbable. Additionally, solubilized CoQ10 in oil formulations show enhanced bioavailability. Coq10 protects the mitochondria and low levels of Coq10 produce mitochondrial dysfunction, reducing adenine triphosphate production. Various chronic diseases respond positively to Coq10 supplementation. Systematic reviews and clinical trials show persons taking statin medication have deficient levels of Coq10 and Coq10 supplementation decreases the negative side effects of statins. Unfortunately, many clinicians do not understand that the statin drugs block the rate-controlling enzyme of the mevalonate pathway, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMG-CoA reductase) whose detrimental consequences are broader than muscle-related adverse events. Providing significant improvement in endothelial function, Coq10 supplementation has been shown, also, to be efficacious in persons with heart failure. We argue in our medical communities; a perceptual shift is urgently needed, providing a positive approach to Coq10 supplementation with statin drug users and chronic disease patients.

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Tolerance of high-dose (3,000 mg/day) coenzyme Q10 in ALS

Cited by 143 publications

References 8 publications

Coenzyme Q10 supplementation reverses age-related impairments in spatial learning and lowers protein oxidation

Coenzyme Q10 supplementation reverses age-related impairments in spatial learning and lowers protein oxidation

Redox Modifier Genes and Pathways in Amyotrophic Lateral Sclerosis

The Role of Coenzyme Q10 Supplementation with Statin Drug Use and Chronic Diseases

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