The Vascular Benefits of Mitochondrial-Targeted Antioxidants

Vascular impairments are the cause of many modern-day ailments. Heart disease, atherosclerosis, cognitive decline, stroke — all can be tied in some way to a reduced ability of blood vessels to carry blood and oxygen throughout the body. In general, this is referred to as endothelial dysfunction (the endothelium is the inner layer of our blood vessels that regulates the ability to relax, or vasodilate).

Another vascular disease where endothelial dysfunction is prominent is called peripheral artery disease, or PAD. PAD is characterized by the buildup of plaque in leg arteries and a narrowing of the blood vessels, which reduces blood flow to lower extremities. This buildup in plaque can be attributed, in large part, to endothelial dysfunction. Reduced leg blood flow is problematic, and individuals with PAD have reduced exercise capacity and lower leg pain during physical activity.

One potential cause of PAD and the associated endothelial dysfunction is oxidative stress. Oxidative stress is a state where our body is producing a greater number of cell-damaging oxygen free radicals (reactive oxygen species or ROS) than our antioxidant system can handle. People with PAD may have a higher production of ROS and reduced antioxidant capacity. In particular, the mitochondria are proposed to be a major source of vascular ROS, especially in people with PAD.

If the mitochondria are the source of these “toxic” ROS that cause endothelial dysfunction and other PAD-related symptoms, then it seems logical that targeting the mitochondria with a molecule that has antioxidant properties could be beneficial for reducing oxidative stress and improving endothelial function.

Enter MitoQ. MitoQ is a compound that has been gaining attention and renown in the research world, particularly in the areas of cardiovascular physiology/disease. A mitochondrial-targeted antioxidant, MitoQ is able to cross the mitochondrial membrane, get inside the mitochondria, and “scavenge” excess ROS production within these cellular powerhouses.

By reducing excess ROS production, MitoQ can improve vascular health and function. This is because ROS negatively impact endothelial function by reducing bioavailability of nitric oxide (NO) — a molecule our body produces that is essential for proper vasodilation of blood vessels, among other beneficial properties. Excess ROS and oxidative stress are a major cause of endothelial dysfunction in a variety of diseases.

How MitoQ works. Source:

The efficacy of MitoQ for vascular health has been demonstrated in humans. A study published in 2018 gave healthy adults MitoQ supplements for 6-weeks, and found that it lowered oxidative stress, improved endothelial function and reduced arterial stiffness. This was in adults who, being categorized as “healthy”, likely had minimal baseline dysfunction or stiffness. Pretty promising.

Another MitoQ study, just published in the American Journal of Physiology: Heart and Circulatory Physiology, looked at whether this antioxidant compound could improve endothelial function in people with PAD. An important topic since, if effective, MitoQ could reduce disease burden not just in PAD, but a variety of vascular disorders.

Participants in this study (5 men and 6 women who were 66 years of age on average) with PAD were given an acute dose of MitoQ (80g) or a placebo in a randomized, crossover design. Baseline measurements included blood draws to assess total antioxidant capacity, levels of a specific antioxidant called superoxide dismutase (SOD), and levels of oxidative stress by measuring a compound called malondialdehyde (MDA). This would assess how effective MitoQ was at increasing antioxidant capacity and reducing oxidative stress.

Arterial stiffness was measured in the central arterial tree (using carotid to femoral pulse-wave velocity), the lower limb vasculature (using carotid to ankle pulse-wave velocity), and the arm (using carotid to radial pulse-wave velocity). Increased pulse-wave velocity is a marker of elevated arterial stiffness, which can contribute to cardiovascular disease risk.

Endothelial function in the brachial and popliteal (behind the knee) artery was assessed using flow-mediated dilation (FMD), which tests the ability of the vessels to dilate in response to a large increase in blood flow.

Other important outcomes included exercise capacity (maximal walking time and distance) and time to onset of leg pain during the walking test — an indicator of exercise tolerance. Before, during, and after exercise, a technique called NIRS was used to measure skeletal muscle tissue oxygenation (saturation) and oxygen utility.

All of these measures were repeated 40-minutes after MitoQ ingestion (or 40-minutes after the placebo).

MitoQ Improves Vascular Function

The first thing to note is that the supplement was well-tolerated by all participants (no side effects) — a seemingly trivial result but important if we are talking about clinical application. You can’t get people to take something that causes negative side effects.

After consuming MitoQ, both measures of endothelial function (brachial and popliteal artery FMD) improved. This suggests that the upper limb and lower limb vasculature were afforded benefits from MitoQ.

Average (top) and individual (bottom) values for brachial and popliteal artery FMD after placebo (PL) and MitoQ (MQ)

Participants were able to walk longer and further after MitoQ, and they were also able to walk longer before experiencing leg pain. So, it appears that MitoQ also improves exercise capacity and tolerance.

Antioxidant levels also increased. SOD concentration increased after MitoQ, while total antioxidant capacity was not significantly changed. MDA, the marker of oxidative stress used in this study, didn’t significantly change either.

Average (top) and individual (bottom) results for walking time, distance, and time to leg pain (COT) after placebo (PL) and MitoQ (MQ0

Other measures that didn’t change: systolic and diastolic blood pressure, all three measurements of pulse-wave velocity (arterial stiffness), resting HR, and oxygen saturation/utilization.

The last result sticks out — exercise capacity and tolerance improved without any apparent change in the muscle’s ability to receive or extract (utilize) oxygen. This seems to suggest some other mechanism is working to improve exercise capacity. However, the only muscle measured in this study was the gastrocnemius, and it’s very likely that other muscles that weren’t measured may have improved oxygen utilization after MitoQ.

A Mito Cure?

This study gives us more interesting data on the promising effects of MitoQ — extending findings to a clinical population with PAD. In this disease, MitoQ may improve endothelial function, antioxidant capacity (at least SOD), and increase exercise capacity. These are all important outcomes for PAD patients, but in any disease state really.

Even though arterial stiffness didn’t improve, I don’t think that means a lot in the context of this study. Typically, arterial stiffness is caused by structural changes in the vasculature that occur over a long period of time. Therefore, we may not expect stiffness to change much after acute antioxidant supplementation. A supplementation period of 6 weeks or more may be needed — and is supported by the chronic supplementation study I cited earlier (in which stiffness was reduced).

Should YOU take MitoQ?

I’m not sure I can give a definitive answer, especially just relying on these two studies (out of the hundreds that have been done on MitoQ…maybe a review is in order). It’s available as an over-the-counter supplement, so anyone can buy it. However, I think the data are mixed on whether healthy people can actually benefit from antioxidant supplementation. Furthermore, if you’re engaged in exercise training, there is even evidence that antioxidant supplementation may be harmful. Sure, ROS can be detrimental at high amounts, but some are required for cell signaling and adaptive responses. It’s not always a case of “less is better.”

In the case of dysfunction and disease, however, I think that mitochondrial-targeted (hence more “specific”) antioxidants hold a big potential for a variety of diseases that are characterized by mitochondrial dysfunction, oxidative stress, and inflammation (i.e. most diseases). Where less specific antioxidants like vitamin C and E have failed, MitoQ may hold more promise.

More data will come out as this “supplement” gains more attention, and it will be interesting to see the stories written and expanded upon in this rapidly-developing research area.

No, this post was NOT sponsored by MitoQ, but if they’d like to sponsor this blog, feel free to reach out 🙂

Studies cited:

Rossman MJ, Santos-parker JR, Steward CAC, et al. Chronic Supplementation With a Mitochondrial Antioxidant (MitoQ) Improves Vascular Function in Healthy Older Adults. Hypertension. 2018;71(6):1056–1063.

Park SY, Pekas EJ, Headid RJ, et al. Acute mitochondrial antioxidant intake improves endothelial function, antioxidant enzyme activity, and exercise tolerance in patients with peripheral artery disease. Am J Physiol Heart Circ Physiol. 2020;319(2):H456-H467.

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