Should You Supplement With Alpha-Lipoic Acid? - Rhonda Patrick

Okay, so the next question that was a deep dive was submitted by Olga, and Olga says, hi Rhonda, you mentioned that you're taking alpha-lipoic acid. Could you please explain the benefits and risks of supplementation? So alpha-lipoic acid, or ALA for short, it's an endogenous compound that is made in our mitochondria. It's also found in dietary sources including leafy greens. It's found in liver and in red meat. Um, it's best known for its role as a mitochondrial cofactor supporting energy production, through the Krebs cycle, where it helps convert nutrients into ATP. Beyond energy production, alpha-lipoic acid also has several other potential benefits on mitochondrial and cellular health.

So my mentor, the late Bruce Ames, was involved in showing a lot of the beneficial effects of alpha-lipoic acid on mitochondrial health. So from an antioxidant perspective, alpha-lipoic acid is unique in its ability to neutralize free radicals and regenerate other antioxidants. such as vitamin C, vitamin E, CoQ10, and glutathione, which sort of amplifies its overall impact on reducing oxidative stress because it's not just a direct antioxidant that can neutralize free radicals, it also regenerates other antioxidants in the body. This, this, this is critical for protecting mitochondrial integrity, particularly in conditions where there's high cellular stress, and it's one of the mechanistic reasons why alpha-lipoic acid is so beneficial for mitochondria.

It also has anti-inflammatory properties, which can indirectly support mitochondrial health by mitigating low-grade inflammation that contributes to cellular dysfunction over time. And it also interestingly has metal chelating capabilities. It can bind to some heavy metals like iron and copper, thereby preventing these from participating in oxidative reactions that can further damage cells. Iron is a big one because too much free iron can cause massive oxidative stress and be very, very damaging to mitochondria. And so, it's also thought that alpha-lipoic acid really has many different ways in which it is improving mitochondrial health through reducing oxidative stress, including binding up and chelating free iron that's also found within the cells as well.

Another really sort of intriguing aspect of alpha-lipoic acid is its role in reducing advanced glycation end products. So, AGEs, we've talked about these. In great detail in a number of Q&As. They're linked to aging and metabolic disease. So, advanced glycation end products form when there is a reaction between glucose and proteins and lipids. So, it can happen endogenously in the body, particularly if someone's eating a lot of refined sugar, for example. When that when you have blood glucose levels elevated in circulation, the glucose there reacts with collagen lining your blood vessels or collagen lining your myocardium or pericardium surrounding your heart, or interacts with LDL cholesterol lipids. And what happens is it stiffens things. It stiffens the proteins, the collagen.

This plays a role in hypertension. It plays a role in— Diabetes. Reducing cardiac compliance, right? It plays a role in the stiffening of our heart with age, or LDL, it plays a role in making it stiffer, more oxidized. If it interacts with other proteins in our body, it can affect the structure of it and the function of the protein. Also, it can interact with the lipid bilayer on cells and affect transport of nutrients and transport of proteins into the cell. Because the cell membrane becomes stiffer. So, advanced glycation end products, essentially, the point I'm trying to drive home here is they're very damaging. They also can be formed within exogenously. So, you can consume them in food that you're eating.

And, it's the same reaction, it's, you know, if you're heat— especially if heat is in the equation. So, something that has a lot of advanced glycation end products, for example, is bacon. If you fry bacon, on a frying pan or in a skillet, I mean, it's just astronomical levels of advanced glycation end products versus, for example, microwaving it. So, you can eat foods that also have advanced glycation end products. If you see that anything that's caramelized, like a caramelized thing, that's actually advanced glycation end products. I mean, it tastes great, but it's a reaction that's occurring between sugars and proteins, and also fats. And so, it's really another way that you get advanced glycation end products into your system.

So, back to alpha-lipoic acid, we're talking about the role of alpha-lipoic acid in negating advanced glycation end products. So, for example, there was a study in diabetic nephropathy patients. So, these are patients that have kidney problems, and typically those are linked to a lot of advanced glycation end products that have damaged the kidney. So, what was shown is that daily supplementation with 800 milligrams of alpha-lipoic acid was able to reduce serum levels of advanced glycation end products over 12 weeks. There's not a lot of evidence on this. So, I mean, these findings are sort of interesting and promising.

I do think it's important to approach alpha-lipoic acid supplementation within the broader context of overall mitochondrial health strategies, such as you want to, you want to basically do what you can to improve your mitochondria by eating healthy and regular physical activity, high-intensity interval training, for example. You know, these are things that are really good for the mitochondria, and this is just a supplement on top of that, right? All right. So peripheral neuropathy is also something that's connected to advanced glycation end products, typically found in patients with type 2 diabetes. It's a condition where the nerves, the peripheral nerves are damaged, and diabetes is really the major contributing factor for this.

There's evidence supporting alpha-lipoic acid being beneficial, but the evidence is mixed. So a meta-analysis of randomized controlled trials showed that alpha-lipoic acid improved sensory symptoms and demonstrated a dose-dependent response for total symptom scores and overall patient satisfaction. However, it had no significant effect on measures like muscle power or vibration perception threshold or nerve conduction. In contrast, a, a Cochrane review showed that ALA had no effect on nerve damage symptoms or impairment. So that said, given the roles of mitochondrial dysfunction, advanced glycation end products, in diabetic neuropathy. I do think alpha-lipoic acid's ability to improve mitochondrial function and reduce AGEs is pretty plausible.

And it might be more of a preventative measure rather than a treatment for someone that's already got established so much damage and neuropathy, right? It's kind of like, you know, if the ship is already sinking, it's already— it's kind of really hard to patch it up. But if you can prevent the ship from sinking, it's much easier to do that. So, that's how I think of it with alpha-lipoic acid. Unfortunately, a lot of studies that are done are not preventative. They're not giving people alpha-lipoic acid before they have neuropathy and then following them to see if they ever develop it, because that would really be the study that needs to be done. Diabetes, blood sugar regulation.

Studies investigating alpha-lipoic acid's impact on insulin sensitivity and glycemic control do have variable results. So, for instance, patients that have type 2 diabetes, there's studies showing that there's increased insulin sensitivity both acutely after alpha-lipoic acid infusion, and also 1 month after oral treatment. However, meta-analysis of randomized controlled trials using standard blood tests for glycemic markers did have mixed results. So, one meta-analysis showed no changes, while another meta-analysis had reduction— showed reductions in fasting blood glucose, reductions in HbA1c, reductions in insulin concentrations, and also other markers of insulin resistance. So, again, mixed results.

When you're, it probably comes down to a lot of factors: dose of alpha lipoic acid, disease progression, how how healthy are these individuals, right? So there's like a lot of a lot of factors here, and I do think it probably suggests that alpha lipoic acid's efficacy depends on the stage of metabolic dysfunction. I currently, you know, metabolically healthy, and so it's a lot easier for me to take alpha lipoic acid in hopes that it's going to. Improve my mitochondrial efficiency, it's going to improve mitochondrial health, it's going to improve the formation of advanced glycation end products will be lowered, all of those things, right? There's also some preliminary evidence that alpha-lipoic acid also affects blood lipids.

So ALA appears to have a modest but significant effect on lowering cholesterol. So there's a meta-analysis of multiple randomized controlled trials that found doses between 300 milligrams and 1,200 milligrams a day led to reductions in total cholesterol, so about almost 11 milligrams per deciliter reduction in total cholesterol, almost 11 milligram per deciliter reduction in LDL cholesterol, and about a 31 milligram per deciliter reduction in triglycerides. And this is across a range of different populations of people, across a range of different health statuses. So— I did find that data very interesting. ALA has also been shown to reduce inflammatory markers like TNF-alpha, IL-6, C-reactive protein.

Another meta-analysis of multiple randomized controlled trials found reductions in those inflammatory biomarkers. Again, there's not— there's enough data to at least get a meta-analysis, which is good, but it's not like this nutraceutical is as well studied as something like metformin, for example. In terms of safety, there's a systematic review and meta-analysis that pooled data from 71 different randomized controlled trials and found there's no increased risk of adverse events with alpha-lipoic acid supplementation. This is consistent across diverse subgroups, including people with diabetes, people with cardiovascular disease, people with neurological disorders, kidney impairment, even pregnancy.

Although I didn't take it during pregnancy, it's been shown to be safe with no adverse effects across a broad range of people. And so I really think that this sort of broad safety profile suggests that alpha-lipoic acid is safe. And, you know, what its efficacy is in these certain conditions is yet to be determined. Like I said, I do think that its effect on, for example, improving neuropathy or improving HbA1c might have to do with your disease status, right, as well as the dose that you're supplementing with. But I do think your metabolic health is an important factor in this equation as well. Daisy is asking what dose I take and what time of day. So, I take 600 milligrams of alpha-lipoic acid, and I usually take it before bed.

And another— it's been years since I've read this data, so maybe things have changed since then. I'll just take it with a grain of salt. But quite a while ago, over a decade ago, I remember I was doing a lot of research on alpha-lipoic acid. And I came across some data suggesting that unlike other supplements, when you're taking alpha-lipoic acid, typically alpha-lipoic acid, I mentioned it's found in foods, right? It's naturally occurring in foods. We also make it in our body. It's usually complex to protein when it's in foods. But when you take alpha-lipoic acid right after a meal, It does lower its bioavailability. For some reason, it complexes with the proteins and isn't absorbed quite as well, or something along those lines.

I don't, um, I don't know if it makes that big of a difference, but if you're really trying to eke out every last kind of benefit you can, you might want to take it a little bit after you've eaten more, more like maybe 3 hours or so after you've eaten. I actually don't do that. I take it with all of my supplements, and typically, I take those within an hour or 2 after I eat. Mike is asking in the chat how ALA would compare to benfotiamine in terms of combating advanced glycation end products. I think there might be more data if you had to choose between the 2 to go for alpha-lipoic acid. There's just a lot more data on it. It also has other benefits too that are very, I would say, very enticing, right?

I mean, the mitochondrial improvements, the chelating iron, in addition to the advanced glycation end products. And, in fact, there's a rapid-fire question I'm going to get to. I'll go ahead and answer it now. But, someone asked me why I stopped taking berberine. And, the reason is because I decided that alpha-lipoic acid does everything berberine does without without the risk of adverse problems with mitochondria and in fact improves mitochondria. So, I've gotten some of my data back and alpha-lipoic acid, I mean, my HbA1c, it did seem to lower my HbA1c. So, right now, my HbA1c was— the last I measured it was about a month ago or a month and a half ago actually, and it was 4.7. Which is pretty good. And the last time I had done it before the alpha lipoic acid, I think I was like 5, about 5. So, so I do, I do like the alpha lipoic acid.