What do we know about the biological roles of Coenzyme Q10 (CoQ10) in the brain? What is the relevance of CoQ10 to brain function? CoQ10 is a vitamin-like lipid-soluble molecule that is essential for mitochondrial ATP energy production. The brain uses inordinate amounts of energy. Accordingly, CoQ10 is important to brain function [Mantle & Hargreaves 2025].
Guest author Dr. Iain P. Hargreaves is a Senior Lecturer in Clinical Biochemistry at Liverpool John Moores University. His research focuses on mitochondrial function, oxidative stress, and CoQ10 supplementation and metabolism.
Moreover, CoQ10 functions as a potent antioxidant. In the brain, CoQ10 protects lipids and mitochondrial membranes against damage by harmful free radicals [Mantle & Hargreaves 2025]. CoQ10’s biological functions are critical in the brain. The neuronal cells need mitochondrial ATP production. They need protection against oxidative stress. It is noteworthy that both mitochondrial dysfunction and oxidative damage are involved in the pathogenesis of age-related neurodegenerative disorders, e.g., Alzheimer’s disease, amyotrophic lateral sclerosis, multiple system atrophy, and Parkinson’s disease [Mantle, Heaton, & Hargreaves 2022].
Is There a Rationale for Supplementary CoQ10 in Neurological Diseases?
Theoretically, given CoQ10’s role in mitochondrial energy production and antioxidant defense, it should be beneficial to use supplemental CoQ10 in neurological disorders. Studies show depleted levels of CoQ10 in the blood of Alzheimer’s patients, multiple system atrophy patients, and Parkinson’s patients [Mantle & Hargreaves 2022, table 1].
In addition, endogenous CoQ10 synthesis declines in ageing individuals. Lower CoQ10 concentrations may contribute to diminished neuronal energy generation and to increased vulnerability to oxidative damage. The decline in endogenous CoQ10 synthesis strengthens the argument for CoQ10 supplementation [Mantle & Hargreaves 2022].
How Does Supplementary CoQ10 Get to the Brain?
Delivering supplementary CoQ10 to the brain is a big challenge. The reason is that the blood–brain barrier restricts the entry of many substances, including CoQ10, to the brain.
What is the Blood-Brain Barrier? Why Does it Block the Entry of CoQ10?
Basically, the blood-brain barrier (BBB) is an interface that protects the brain from potentially harmful substances. The BBB is tightly regulated.
CoQ10 molecules are quite large molecules. They are too large to diffuse passively across the BBB. This makes it difficult if not impossible for supplementary CoQ10 to reach human brain tissue. To get from the blood to brain tissue, supplementary CoQ10 would need the help of an active transport protein. To date, researchers have not identified any transporters that actively carry CoQ10 across the human BBB [Mantle & Hargreaves 2025].
Thus, there does not exist any clinical trial evidence that oral CoQ10 supplements increase CoQ10 levels in human brain tissue. At present, researchers do not have any no suitable techniques to monitor directly the CoQ10 concentrations in the human brain in vivo. They cannot assess directly whether supplementary CoQ10 crosses the human BBB and reaches human brain tissue [Mantle, Cufflin, Dewsbury, and Hargreaves 2025].
What Is the Difference Between Animal BBB and Human BBB?
Some animal studies do show increased brain CoQ10 levels associated with supplementation. However, this difference between animal studies and human studies may reflect the fact that animal blood-brain barriers are less restrictive than human blood-brain barriers. The BBB in rodents seem to be more permeable than the BBB in humans. This is an important point to keep in mind [Mantle & Hargreaves 2025].
What Is the Difference Between the BBB and the Blood-CSF Barrier?
Yes, this is an important distinction to make. CoQ10 supplementation in humans may result in somewhat increased levels of CoQ10 in cerebrospinal fluid (CSF). This, however, does not correspond to increased CoQ10 levels in the brain tissue itself, which is where more CoQ10 is needed [Mantle & Hargreaves 2025].
What Do BBB Model Systems Show?
Wainwright et al have used an in vitro BBB model system to investigate CoQ10 access to the brain. In their 2D porcine endothelial monolayer cell model, CoQ10 was transported from the blood side to the brain side of the barrier by lipoprotein-associated transcellular transport via interactions with the SR-B1 (Scavenger Receptor) and RAGE (Receptor for Advanced Glycation End products)
receptors [Wainwright, Hargreaves et al 2020].
However, Wainwright et al observers that the CoQ10 then simultaneously flow back to the blood side via the LDLR (low-density lipoprotein receptor) transporter. Thus, the result was no net accumulation of CoQ10 in brain tissue [Wainwright, Hargreaves et al 2020].
When Wainwright et al used using para-aminobenzoic acid (PABA) to induce a deficiency of CoQ10 in the model BBB, they saw that the BBB became leakier. It had disrupted tight junctions and poorer integrity. The leakier BBB did permit increased net CoQ10 transport from the blood side to the brain side [Wainwright, Hargreaves et al 2020].
Are There Alternative Ways to Deliver CoQ10 to Human Brain Tissue?
Intranasal drug delivery involves direct delivery of suitable drugs into the brain provides a mechanism by which drugs can be transported along the olfactory and trigeminal nerves. This method effectively bypasses the BBB. The intranasal delivery route has been effective for the administration of some prescription drugs. But, to date, there have not been any clinical studies of the intranasal administration of CoQ10 [Mantle, Cufflin, Dewsbury, and Hargreaves 2025].
What Does Research on CoQ10 and Neurological Diseases Show?
There are have been some promising results in animal models. However, randomized controlled clinical trials of supplementary CoQ10 for patients with Alzheimer’s disease, amyotrophic lateral sclerosis, and Parkinson’s disease have mostly not shown significant clinical benefit. The explanation may be that supplemental CoQ10 does not reach neuronal tissues, at least not in sufficient concentrations [Mantle & Hargreaves 2022].
Conclusions: CoQ10 and Blood-Brain Barrier
Clearly, CoQ10 is important for brain health.
CoQ10 has an important biological role to play in neuronal energy generation and in antioxidant defense.
Improving the delivery of exogenous CoQ10 to the brain tissue may lead to clinical benefits in patients with neurodegenerative diseases.
Sources
Mantle D, Heaton RA, Hargreaves IP. Coenzyme Q10, ageing and the nervous system: An overview. Antioxidants. 2022;11(1):2.
Mantle D, Hargreaves IP. Mitochondrial dysfunction and neurodegenerative disorders: role of nutritional supplementation. Int J Mol Sci. 2022 Oct 20;23(20):12603.
Mantle D, Hargreaves IP. Coenzyme Q10 and the blood-brain barrier: An overview. J Clin Med. 2025;14(8):2748.
Mantle D, Cufflin N, Dewsbury M, Hargreaves IP. Blood-brain barrier and neuronal model systems for studying CoQ10 metabolism. Antioxidants (Basel). 2025 Dec 28;15(1):41.
Wainwright L, Hargreaves IP, Georgian AR, Turner C, Dalton RN, Abbott NJ, Heales SJR, Preston JE. CoQ10 deficient endothelial cell culture model for the investigation of CoQ10 blood-brain barrier transport. J. Clin. Med. 2020;9:3236.
The information presented in this review article is not intended as medical advice. It should not be used as such.
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