How Supplements Affect Mitochondrial Energy Production

Matthew asked about a variety of supplements that affect mitochondrial health and wanted to just review briefly the supplements' mechanism of action, of how they influence mitochondria. For example, ubiquinol, PQQ, acetyl-L-carnitine, alpha-lipoic acid, and any others.

We'll start with carnitine. L-carnitine is produced in the body from lysine and methionine. It's found in a lot of foods, particularly high in meat products. L-carnitine is important. It plays an important role in being a transporter for fatty acids into the mitochondria. That's its major role. It's forming a transporter to allow fatty acids into the mitochondria so they can be used as an energy source.

It also plays a role in detoxifying potentially toxic metabolites. If you have a buildup of too many acetyl residues, then it can become a little bit toxic. That's not usually a problem unless someone's doing a complete ketogenic diet and maybe they have some other metabolic problems on top of that. But generally, you're not going to get a buildup of too many of those acetyl groups. Those acetyl groups are used for other things like epigenetic regulation as well. The L-carnitine does play a role in that detoxification, but I don't think that's a big mechanism of action.

L-carnitine's also involved in stabilizing cell membranes, and it plays a role in, of course, ketone production, fatty acid synthesis, anything that's involved in energy production using fatty acids. There's been a variety of intervention studies. A lot of them have been small, looking at carnitine supplementation in the range of 1 to 4 g a day along with carbohydrates. It seems as though this helps because insulin—when you eat carbohydrates, you increase insulin—helps L-carnitine get into muscle cells. It kind of helps with some of the muscle effects of L-carnitine. The study showed that women that took it had an increase in muscle mass, and they also had improvements in cognitive function. There's been a meta-analysis looking at L-carnitine supplementation showing that people that were overweight and/or obese had reductions in body weight and waist size and total amount of body fat.

The other supplement is ubiquinol. This is CoQ10. It's found in oxidized form or in reduced form, so ubiquinol versus ubiquinone. Ubiquinol is a little more bioavailable, but both can do the job. CoQ10 is a coenzyme. It's found in our mitochondria. It's important for passing electrons in our mitochondria to make energy. It plays a role in the oxidative status of mitochondria. Statins inhibit the ability to make ubiquinol, make CoQ10 in the body. That is very, very important and is why people that are using statins should be supplementing with a ubiquinol or a ubiquinone supplement as well.

And then alpha-lipoic acid, it's a thioctic acid. It's a short-chain fatty acid that's produced in the mitochondria. It's also found in a variety of foods like broccoli, spinach, potatoes, tomatoes, Brussels sprouts. There's some animal-derived dietary sources as well, including liver, particularly organ meat and some red meat as well. It is a cofactor involved in your mitochondrial energy production, and it's involved in mitochondrial biogenesis, which is the growth of new mitochondria. It plays a role in metabolism, mitochondrial metabolism.

It's also got very strong antioxidant capabilities. It can neutralize free radicals, which are produced by the mitochondria. It plays a role in regenerating vitamin C. Once vitamin C is oxidized, it can be reduced and used again. It does the same thing for glutathione and the same thing for vitamin E. It plays a role in basically prolonging the half-life of these antioxidants like vitamin C and vitamin E and glutathione so that they can be used over and over again.

I mentioned it plays a role in energy metabolism. It also has anti-inflammatory effects as well as chelating some metal ions. It's known to bind some ions like iron and copper, reducing their availability to participate in producing free radicals, particularly with respect to iron. A lot of free iron can be very oxidative and cause a lot of oxidative stress. It plays a role in that and also reduces advanced glycation end products.

There's a variety of clinical studies showing that it helps people with, for example, diabetes that have high advanced glycation end products, which play a role in neuropathy and a variety of—in the eyes and the kidneys. Just the high levels of glucose will lead to advanced glycation end products, which then damage tissues. Alpha-lipoic acid sort of negates that response. It prevents the formation of those advanced glycation end products. It also plays a role in skin aging as well.

PQQ is one of the main last supplements we're going to talk about. PQQ cannot be synthesized in the body. It has to be obtained through diet. It's found in fermented products, a lot of fermented foods. It's also found in some fruits and vegetables, milk and eggs. It's a compound that has been identified to play an enzymatic role in a variety of enzymes that are converting NADH to NAD+. It plays a role in NAD metabolism.

There's been some studies we've talked about in the past on PQQ supplementation reducing C-reactive protein, reducing IL-6, reducing oxidative biomarkers like lipid oxidation in plasma. It's also been shown to improve mitochondrial oxidation as well as improve cognitive performance and endurance in some small studies. There's a lot of very small studies on this. I would say it's not like large studies have been done and it's clear PQQ is going to improve things. These are very small studies. There's just not a lot of information available. It's still a work in progress, and I would say it's promising, but you never know. You might get some larger studies and it's not repeatable, right? It's still something I would say take with a grain of salt.

And then omega-3, of course, has an effect on mitochondria as well. Mitochondrial membranes are composed of a high proportion of DHA. Omega-3 plays a role in mitochondrial health as well.