Show Notes
A molecule that is cleared from your blood in 90 minutes should not still be changing your biology weeks later. That mismatch is the whole story of alpha lipoic acid.
Somewhere in a lab, a group of old, tired rats, the rat equivalent of a sedentary 75 year old human, were given a single compound and started moving around their cages like young animals again. One of the scientists joked that they got up and danced the Macarena. That compound sits on pharmacy shelves everywhere, labeled as an antioxidant. In this solo deep dive, Dr. Ravi Kumar goes to the actual literature to find out what alpha lipoic acid really does inside your cells, and admits that when he looked it up himself, he had it almost completely backwards.
The pharmacokinetics are what break the simple antioxidant story. Oral lipoic acid has a half-life of roughly 30 minutes and is essentially gone from the bloodstream within an hour and a half. The amount of direct free radical mopping a dose like that could do, spread across trillions of cells, is trivial. The math does not work. What does work is hormesis. A brief oxidative nudge from the molecule pulls a cellular fire alarm called NRF2, a master regulator that switches on hundreds of your own genes for antioxidant production, detoxification, and repair, and those genes keep working long after the lipoic acid itself has cleared. Lipoic acid is not the firefighter. It is the person who pulls the alarm.
There is a second alarm too. AMPK, the master fuel gauge inside every cell, is the switch that a lot of the benefits of fasting and exercise run through. Lipoic acid flips that same switch in muscle and liver, telling cells to burn fat, take up sugar, and build more mitochondria. In the hypothalamus it does the opposite, quieting AMPK down, which turns out to reduce appetite.
Unlike vitamin C, humans never lost the ability to make this molecule. An enzyme called lipoic acid synthase builds it from scratch inside your mitochondria, where it becomes the swinging arm on pyruvate dehydrogenase that physically passes fuel through the door into the Krebs cycle. Without it, the fuel piles up outside and the furnace goes cold. That production capacity declines with age, disease, and metabolic stress, which is why researchers call lipoic acid conditionally essential rather than essential.
The clearest human evidence is in diabetic neuropathy. Germany has approved lipoic acid as thioctic acid for this indication for decades, and the randomized trials go back to ALADIN in 1995, with the follow-up Sydney trial landing on 600 milligrams a day of oral lipoic acid as the sweet spot for benefit and tolerability. Dr. Kumar is careful to size the rest of the evidence honestly. The weight loss data is real but modest, a trial of 360 obese adults found the higher dose group lost about 2% more weight than placebo over 20 weeks, nowhere near what the GLP-1 medications do. The dancing-rat rejuvenation study was in rats, not people. And there are real cautions: lipoic acid can stack with glucose-lowering drugs, and in genetically susceptible people, especially those of East Asian descent, it carries a rare risk of insulin autoimmune syndrome.
His bottom line is that lipoic acid reduces the damage from diabetes without fixing the diabetes, and that for most people the better first move is protecting their own production with movement and real food.
Episode Resources
- Dr. Ravi Kumar’s Website
- Dr. Ravi Kumar on LinkedIn
- The Dr Kumar Discovery on YouTube
- The Dr Kumar Discovery on Apple Podcasts
- The Dr Kumar Discovery on Spotify
In this episode, you will discover:
- The 90 minutes versus weeks problem: Oral lipoic acid has a half-life of about 30 minutes and is cleared from your blood within an hour and a half, yet its effects can persist for days or weeks, which is the clue that it is not working the way the label says
- It is a signal, not a scrubber: The benefit comes less from personally neutralizing free radicals and more from acting as a tiny controlled stress that switches on your own defense genes
- NRF2, the foreman of your defense department: A brief oxidative nudge activates NRF2, which turns on hundreds of your own genes for antioxidants, detoxification, and repair that keep working long after the molecule is gone
- Your body already makes it: Unlike vitamin C, we never lost the gene, and an enzyme called lipoic acid synthase builds lipoic acid from scratch inside your mitochondria
- The swinging arm on the furnace door: Lipoic acid is the arm on pyruvate dehydrogenase that physically passes pyruvate into the Krebs cycle, which makes it essential for turning food into energy
- Why it becomes conditionally essential: Your ability to make it falls as mitochondria decline with age, disease, and metabolic stress, which explains exactly who benefits from supplementing and who does not
- Where it comes from in food: The richest sources are the most mitochondria-dense tissues, organ meats like kidney, heart, and liver, plus chloroplast-rich dark leafy greens such as spinach and broccoli
- AMPK, the exercise impersonator: Lipoic acid flips the same cellular fuel gauge that fasting and exercise flip, and quiets it in the hypothalamus, which is where the appetite effect comes from
- The strongest clinical evidence: ALADIN in 1995 and the Sydney trial support 600 milligrams a day for the burning and tingling of diabetic neuropathy, and Germany has approved it as thioctic acid for decades
- The R form matters: Cheap supplements are often a fifty-fifty mix of the natural R form and a synthetic S form your body does not use well, so look for R lipoic acid, R alpha lipoic acid, R-LA, or sodium R lipoate
- Timing and dose: Food significantly blunts absorption, so take it on an empty stomach 30 to 60 minutes before a meal, and treat 600 milligrams a day as the evidence-based ceiling
- Two sulfurs, one rare risk: The reactive sulfur pair can trigger insulin autoimmune syndrome, also called Hirata disease, a risk that is much more common in people of East Asian descent
Key Takeaways
- Alpha lipoic acid is not really the antioxidant the bottle says it is. It is a hormetic molecule, a small controlled stress that wakes up your own defenses instead of doing the work for you
- The pharmacokinetics give it away. A half-life of about 30 minutes and clearance within 90 cannot explain effects that last days to weeks, so the mechanism has to be signaling, not direct chemistry
- NRF2 is the main alarm it pulls, switching on hundreds of antioxidant, detoxification, and repair genes. AMPK is the second, pushing muscle and liver toward burning fat, taking up sugar, and building mitochondria
- In its reduced form, lipoic acid recharges spent vitamin C and vitamin E and regenerates glutathione and coenzyme Q10, sitting one rung up the ladder from the rest of the antioxidant crew
- Your mitochondria already make lipoic acid using lipoic acid synthase, and it is bolted onto pyruvate dehydrogenase as the arm that feeds fuel into the Krebs cycle. Production declines with age and metabolic stress, which makes it conditionally essential
- Diabetic neuropathy is where the human evidence is strongest. ALADIN in 1995 showed intravenous lipoic acid reduced symptoms over three weeks, and the Sydney trial confirmed 600 milligrams a day orally. The long-term picture is more mixed, because lipoic acid reduces the damage from diabetes without fixing the diabetes
- The weight loss effect is real but small. A randomized trial of 360 obese adults found about 2% more weight lost than placebo over 20 weeks, nowhere near what GLP-1 medications achieve
- If you supplement, get the form, timing, and dose right: R lipoic acid or sodium R lipoate, on an empty stomach 30 to 60 minutes before a meal, at or below 600 milligrams a day, since higher doses tend to cause nausea. A biotin-containing multivitamin is a cheap hedge on long-term high-dose use
- Two cautions matter. Lipoic acid lowers blood sugar and can stack with insulin and other glucose-lowering drugs, and in genetically susceptible people, disproportionately those of East Asian descent, it can trigger insulin autoimmune syndrome, or Hirata disease
- If you are young and metabolically healthy, your own production is likely enough. Protect it with the boring free stuff: move your body, do not smoke, do not drown your cells in constant sugar, and eat the greens and organ meats that carry it naturally
Transcript
[00:00 –> 01:27] Dr. Ravi Kumar: So a group of researchers took a bunch of old, tired rats, the rat equivalent of a sedentary 75 year old human, and fed them a single compound called alpha lipoic acid. Within a few weeks, those old rats were moving around their cages like young, spry little rats again. One of the scientists joked that the old rats got up and danced the Macarena. Now, if you buy this same supplement, alpha lipoic acid, it’s basically sold to you as an antioxidant. And that is true, it is an antioxidant, it’s actually a very powerful antioxidant, but when you swallow it, it’s gone from your blood within an hour and a half. So how does something that disappears in an hour and a half wake up an aging human body for weeks like it did in those rats? And should we be taking this supplement? Those are the questions that I’m gonna answer in this episode. So let’s get into it. My name is Dr. Ravi Kumar. I’m a neurosurgeon in search of the causes of human illness and the solutions that help us heal and thrive. I want you to join me on a journey of discovery as I turn over every stone in search of the roots of disease and the mysteries of our resilience. The human body is a mysterious and miraculous machine with an amazing ability to self heal. Let us question everything and discover our true potentials. Welcome to the Dr Kumar Discovery.
[01:30 –> 02:26] Dr. Ravi Kumar: Okay, so before we talk about alpha lipoic acid and whether we should be taking it or not, I want to give you a quick disclaimer. This podcast is for informational purposes only, and it isn’t meant to diagnose or treat any medical condition. My aim here is to bring clarity to complex health topics so you can think more clearly about your health and make informed decisions with your own healthcare provider. I believe knowledge is power, and I want to empower you to take an active role in your own health journey. Also, should say that this podcast is separate from my role as assistant professor at UNC. Okay, so I know that some of you are probably thinking, alpha lipoic acid, isn’t that just another antioxidant in a bottle? Another pill that the supplement industry wants to sell me? And honestly, a long time, that’s pretty much how I thought about it too. I had filed it away in my mind, next to all the other antioxidants, as may be useful, but nothing special. Nothing that I would go out of my way to find, buy, and take.
[02:27 –> 03:18] Dr. Ravi Kumar: But when I actually went to the literature and looked it up myself, I found out that I had it almost completely backwards. So stick with me, because the story behind alpha lipoic acid is very interesting, and possibly very biologically useful. So let’s start with the most basic question. What is alpha lipoic acid? Well, chemically, it’s a small sulfur containing molecule. You’ll also see it called thioctic acid, or just lipoic acid, or on some labels, ALA. The most important part, the business end of this molecule, is a tiny ring with two sulfur atoms, and they sit right next to each other. And these two sulfur atoms are the workhorses that produce almost everything interesting about this molecule, both the good things and the potentially risky things. Now here’s the part most people never hear. Your body actually makes alpha lipoic acid.
[03:19 –> 04:17] Dr. Ravi Kumar: Its actual day job, the reason your body evolved to make it at all, is to be a permanent part of the machinery used to make energy inside your mitochondria. This is how it works. When you eat carbohydrates, your body basically breaks those carbohydrates down into glucose, and glucose gets converted to pyruvate. Pyruvate is basically processed fuel sitting at the door of your biochemical furnaces. Pyruvate dehydrogenase is an enzyme that acts as the gatekeeper at that door. It takes pyruvate and feeds it into the Krebs cycle, which is the furnace inside your mitochondria that produces most of the energy that keeps you alive. And lipoic acid is the little swinging arm on that gatekeeper that physically passes the fuel through the door and into the furnace. So think about what that means. Without lipoic acid, the ability to feed fuel into your furnace is hampered. The fuel piles up outside and the furnace goes cold.
[04:18 –> 05:09] Dr. Ravi Kumar: This is not some optional nice to have antioxidant. At the most fundamental level, lipoic acid is essential for turning your food into energy. And it does equally important jobs on a couple of other mitochondrial enzymes too. One that turns amino acids into energy, and another key step in the Krebs cycle. Alpha lipoic acid is, in a very real sense, one of the most important molecules that makes you a functioning, energy producing organism. Now, this raises an obvious question. If lipoic acid is so essential, and if your body needs it to make energy, then surely your body makes most of what it needs. And it actually does. This is the big difference from some of the other nutrients I’ve covered on this show. If you listened to my episode on vitamin C, The Vitamin C Paradox, you’ll remember that we humans actually lost the gene to make our own vitamin C millions of years ago.
[05:09 –> 06:25] Dr. Ravi Kumar: And now, we are completely dependent on our diet to get it. Lipoic acid is the opposite. We never lost the ability to make lipoic acid. Deep in your mitochondria, you have an enzyme called lipoic acid synthase that builds lipoic acid from scratch. So if you make your own, why would anyone ever want to supplement with it? And this is a question that you should ask with any non food based supplement. And in this case, alpha lipoic acid does have a very compelling and interesting biochemical story that might lead us to want to supplement with it. Here’s the first thing. The lipoic acid your body makes does not float around freely. The moment it’s made, it gets bolted directly onto those mitochondrial enzymes that we just talked about, and it stays there doing its gatekeeper job. Your body makes just enough to run the machinery, and essentially none of it spills out into your bloodstream as free lipoic acid. So the pool of lipoic acid that acts as a roving antioxidant, the kind that people are chasing when they buy the supplement and take it, is a completely separate pool. And historically, that free pool of alpha lipoic acid came from one place: food. And this is where the evolutionary picture gets very interesting. So where do you find lipoic acid in food?
[06:25 –> 07:24] Dr. Ravi Kumar: Well, turns out the richest sources are exactly the tissues that are densely packed with mitochondria. We’re talking about organ meats, like kidney, heart, liver. For almost all of human history, when our ancestors killed an animal, they did not toss out the organs. They actually ate them first. They were the most prized part of that kill. And they were eating, without knowing it, the most mitochondrial rich, lipoic acid rich tissue available. And on the plant side, the best sources are the parts that are rich in the plant equivalent of mitochondria, which is the chloroplasts. So we’re talking about dark leafy greens like spinach and broccoli. So the ancestral human, eating nose to tail and eating their greens, was getting a steady trickle of free lipoic acid that most of us simply don’t get today. Now, another thing to consider is that there’s good evidence that your ability to make lipoic acid declines the older you get, because the number and health of your mitochondria declines as you age.
[07:25 –> 08:18] Dr. Ravi Kumar: Researchers have a phrase for a nutrient like this. It’s called conditionally essential, meaning your body makes plenty of it when you’re young and healthy. But under certain conditions, like aging, metabolic stress, disease, your own production may no longer keep up with demand. And insufficient lipoic acid production can throw a real monkey wrench into the system. In a world of constant sugar, the very furnace that lipoic acid was built to feed gets choked out by the inability to get the fuel into the furnace in the first place. Now keep that concept in the back of your mind, because it’s gonna explain almost everything about who actually benefits from taking this molecule. Okay, so let’s talk about free lipoic acid. This is the antioxidant story. Because we have to understand the popular version that sells supplements, before I can show you why it’s actually incomplete. Lipoic acid has one very special trick.
[08:18 –> 09:16] Dr. Ravi Kumar: Most antioxidants only work in one neighborhood of the body. Vitamin C, for instance, works in the watery spaces, the blood and inside the cells. Vitamin E works in the fatty spaces, like your cell membranes. Lipoic acid works in both. It’s comfortable in water and in fat, and that earned it a nickname decades ago called the universal antioxidant. And it has a second trick that connects directly back to my vitamin C episode. Remember how I described vitamin C as a firefighter that neutralizes a free radical and then gets recharged so it can go back and do the work again? Well, one of the things that recharges vitamin C is lipoic acid. Lipoic acid, in its reduced form, can hand electrons back to spent vitamin C and vitamin E, and also regenerate glutathione and coenzyme Q10. So lipoic acid does not just put out fires itself, it sits one rung up the ladder and recharges the whole antioxidant crew.
[09:17 –> 10:31] Dr. Ravi Kumar: People call this the antioxidant network. It’s a really elegant system for regenerating antioxidant capacity. And for a long time, this was the entire pitch for lipoic acid. It was a universal antioxidant that recharged everything, so if you took it, you’d mop up your free radicals everywhere in your body. It was a beautiful story, but there was just one problem with it. When you actually measure what happens when someone swallows a capsule, the whole story falls apart. So when you take oral lipoic acid, your body absorbs only a fraction of it, and it clears the rest of it out of your bloodstream almost immediately. The half-life is something like 30 minutes. And pharmacokinetic studies show the same thing again and again. It peaks in your bloodstream after oral intake, and then it’s gone. So that poses a conundrum. We’re told that lipoic acid is a powerful antioxidant that protects your whole body, but it’s present at meaningful levels for about an hour and a half after you take it. The amount of direct free radical mopping that a dose like that could possibly do, spread out across trillions of cells in your body, is honestly trivial. The math just doesn’t work. And yet, that rat study that I opened up with in the corresponding human data shows effects that last for days and weeks.
[10:31 –> 11:31] Dr. Ravi Kumar: So how can something that’s cleared in an hour and a half from your bloodstream give weeks or days of effect? Well, there’s a powerful reframe here, and let me tell you about it. Lipoic acid may not work mainly by being an antioxidant at all. It may work by being a tiny, controlled stress. Let me explain what I mean, because this idea called hormesis is one of the most important concepts in all of health. And once you see it, you will see it everywhere. Hormesis is the principle that a small dose of something stressful makes you stronger. It is the cellular version of what doesn’t kill you makes you stronger. Exercise, for example, is hormesis. When you lift a weight, you cause tiny bits of damage and stress in your muscle, and your body responds by rebuilding it stronger than before. A vaccine is also a hormesis. A tiny, harmless exposure trains your immune system to be ready. The stress is not the bad part. The stress is the signal that then makes you stronger. So what does lipoic acid do when you take it orally?
[11:32 –> 12:49] Dr. Ravi Kumar: Well, it gives your cells a brief, mild, oxidative nudge, and that nudge trips an alarm. Specifically, it activates a protein called NRF2. I want you to think of NRF2 as the foreman of your cell’s entire defense department. Normally, the foreman sits quietly and lets his workers work. But when it smells smoke, even a little bit of smoke, NRF2 springs into action and switches on hundreds of your own genes. These are genes like glutathione, or other genes that build antioxidant systems, or manage detoxification and repair. Do you see the difference here? In my vitamin C episode, vitamin C is the firefighter. It runs into the building, puts out the fire with its own hands. Lipoic acid is not really the firefighter. Lipoic acid is the guy who pulls the fire alarm. It does not put out much of the fire itself. It wakes up the entire fire department, which are your own genes, your own enzymes, and then they do the work, and they keep working long after lipoic acid is gone from your body. That is how a molecule that vanishes in less than two hours after oral supplementation can change your biology for weeks. So it’s not the actual antioxidant function that helps you, it’s the wake up to the whole antioxidant and repair system.
[12:49 –> 13:54] Dr. Ravi Kumar: And there’s a second alarm that it pulls, which matters enormously for metabolism. There’s a master fuel gauge inside every one of your cells called AMPK or AMP kinase. When your cellular fuel runs low during fasting, during exercise, AMPK flips on and tells the cell to start burning fat, take up sugar, or build more mitochondria, it is the switch that a lot of the benefits of fasting and exercise run through. And lipoic acid flips that same switch. In your muscles and liver, it nudges AMPK in the direction of burning fuel and pulling sugar out of the bloodstream, which again is not lipoic acid doing the work directly, it’s lipoic acid impersonating the signal of exercise and fasting, and letting your own machinery respond. So when you hear me say it’s a hormetic molecule, this is what I mean. It does not hand your body a finished product. It hands your body a message. And the message is, time to get stronger. So now that you understand the real mechanism, the clinical evidence is gonna make a lot more sense.
[13:54 –> 15:04] Dr. Ravi Kumar: Because if lipoic acid works by tuning up tired, stressed mitochondria and waking up your own defenses, then the people who should benefit most are those whose mitochondria are under the most stress. And there’s no better example of this than diabetes. The single strongest body of evidence for lipoic acid, by far, is in diabetic neuropathy. That is the nerve damage, the burning, tingling, numbness, and pain in feet and hands that develops in many people with long standing diabetes. As a neurosurgeon, I’ve seen up close what chronically high blood sugar does to nerves. It is, at its core, a story of oxidative stress and failing mitochondria inside the nerve cell, which is exactly the kind of fire that lipoic acid is built to address. And this is not a fringe theory. In Germany, lipoic acid, under the name thioctic acid, has been an approved prescription treatment for diabetic neuropathy for decades. And lipoic acid’s effect on diabetic neuropathy has been studied in a long series of properly randomized controlled trials. The first big one was called ALADIN, and it was published in 1995.
[15:04 –> 16:20] Dr. Ravi Kumar: And it found that intravenous lipoic acid over three weeks reduced symptoms of diabetic neuropathy. A follow-up study called the Sydney trial confirmed that oral lipoic acid, at 600 milligrams per day, hit the sweet spot and offered great benefit with great tolerability. The longer term picture is a bit more mixed, and this makes sense because lipoic acid is reducing the oxidative damage from diabetes, but it’s not fixing the diabetes. That is something you have to do with diet and lifestyle. And a couple of trials showed that when lipoic acid was used long term, you didn’t see the benefits that you saw when you used it short term. So how do I read all of this together? Well, lipoic acid, especially at 600 milligrams a day, fairly reliably reduces the symptoms of diabetic neuropathy in the short to medium term, particularly that burning and tingling sensation that you get from diabetic neuropathy. And it’s remarkably safe. Whether it dramatically halts the long term march of the disease is less certain. So it may not be a slam dunk, but for a condition where other options are mostly drugs that just numb the pain, a safe molecule that may actually address the underlying mitochondrial stress is worth a serious conversation with your doctor.
[16:21 –> 17:24] Dr. Ravi Kumar: And lipoic acid may have effects upstream for dealing with blood sugar and weight, which makes sense given the AMPK story I told you about. In the muscle, lipoic acid helps move sugar out of the blood and into the cell. A study in the Journal of Diabetes back in 1996 showed it enhanced insulin stimulated glucose uptake in insulin resistant muscles. And human work has echoed that it can modestly improve insulin sensitivity. And there’s an appetite effect with lipoic acid, which is something that I was really surprised to find. Remember that fuel gauge AMPK that we were just talking about? Well, in your muscles, lipoic acid nudges it on. But in a specific part of your brain called the hypothalamus, it does the opposite. It quiets AMPK down, and that turns out to reduce appetite. A paper in Nature Medicine in 2004 showed that lipoic acid caused profound weight loss in rodents by reducing how much they ate and increasing how much energy they burned, working right through that hypothalamic switch.
[17:24 –> 18:32] Dr. Ravi Kumar: Now, before you run out and buy lipoic acid as a weight loss drug, let me just be clear with you. The human weight loss data is real, but is very modest. A randomized trial of 360 obese adults found that the higher dose group lost about 2% more weight than the placebo group over 20 weeks. That’s not nothing, but it’s not magic, and it’s nowhere near what the new GLP-1 medications can do. The way I think about this is lipoic acid is not a weight loss drug. It’s a metabolic tune up that might give a small nudge in the right direction, mostly in people who are already metabolically stressed. Which brings us all the way back to those dancing rats that I talked about in the very beginning of the show. That work came largely out of a lab studying why mitochondria decay as we age. The researchers took old rats and gave them lipoic acid together with another mitochondrial nutrient called acetyl-L-carnitine. And then in a paper published in 2002, they reported that the old animals had better functioning mitochondria, less oxidative stress, better memory on tests, and an increase in ambulatory activity.
[18:33 –> 19:37] Dr. Ravi Kumar: The old sluggish rats started moving around like younger animals. Now, these are rats, not people. And I always wanna be careful not to oversell an animal study. But the reason it fits so beautifully is the mechanism that we already talked about in this episode. Old mitochondria are exactly the tired, stress system that a hormetic wake up call is most likely to help. The lipoic acid is not pouring new energy into that rat. It’s sending an old, dimmed down system the signal to switch its defenses and its fuel burning back on. And notice the pairing. Lipoic acid plus acetyl-L-carnitine, which shuttles fats for energy burning into the mitochondria. That is not random. Lipoic acid wakes up the furnace, and then the carnitine helps shuttle the fat into that furnace to burn more energy. Alright. So I hope all that made decent sense, and if it didn’t, don’t worry about it. We’re gonna move on to the practical part, and I think a lot of this should pull together for you. So should you be taking alpha lipoic acid?
[19:37 –> 20:33] Dr. Ravi Kumar: Well, the answer is, it depends. I would say first, if you are fairly healthy or young, your own mitochondria are making what you need. And the most sensible thing you can do is to protect that production. That means the boring free stuff. Move your body, don’t smoke, don’t drown your cells in constant sugar, and eat the foods that carry natural lipoic acid and support the whole system, like dark leafy greens and organ meats, if you’re willing to eat them. You should be living your life the way you envisioned your great ancestors lived, and in that setting, you most likely won’t need to take lipoic acid, just as they didn’t need to take it. Now, if you’re in a figurative metabolic hole and need a boost, lipoic acid may help. So here’s what you need to know about supplementing. First is the form. The lipoic acid your body makes is one specific mirror image version of the molecule, and it’s called the R form.
[20:34 –> 22:02] Dr. Ravi Kumar: A lot of cheap supplements are a fifty-fifty mix of the natural R form and a synthetic S form that your body does not make and does not use well. So look for R lipoic acid or R alpha lipoic acid. It can sometimes even be labeled as R-LA, or sodium R lipoate. All of these will be the versions that match what your body actually produces and tends to be better absorbed. The second thing is timing. Food significantly blunts absorption, so it’s best taken on an empty stomach 30 to 60 minutes before a meal. Third is the dose. The number that has the most clinical evidence behind it is that 600 milligrams a day from the neuropathy trials. That’s a reasonable evidence based ceiling for most people. Going higher than that will most likely cause you a little bit of nausea. And then one thing to take note of is that lipoic acid looks structurally similar to the vitamin biotin, and may compete with it a little bit. So if you’re taking high doses of lipoic acid long term, a biotin containing multivitamin is a cheap way to cover your bases. Now, I wouldn’t be doing my job if I didn’t give you some cautions, and there are a couple things that you should know about. First, because lipoic acid lowers blood sugar, if you are diabetic and on insulin or other glucose lowering medications, it can stack on top of those drugs and push your sugar too low. So that’s a conversation that you should have with your doctor if you fall into this category.
[22:03 –> 22:57] Dr. Ravi Kumar: And the second caution ties right back to those two sulfur atoms that I told you to remember about at the beginning of the episode. If you forgot about them, that’s okay. But here’s why they’re important. There is a rare condition called insulin autoimmune syndrome, also called Hirata disease. And in this condition, the body starts making antibodies against its own insulin. And those antibodies can cause unpredictable, sometimes severe drops in blood sugar. And it turns out that compounds containing reactive sulfur groups can trigger it in people who are genetically susceptible. Lipoic acid, with its two sulfurs, is one of those triggers. Since the mid 2000s, a growing stream of case reports, mostly out of Japan, Korea, and Italy, have documented people developing this autoimmune low blood sugar after starting lipoic acid. The genetic susceptibility is much more common in people of East Asian descent.
[22:57 –> 24:16] Dr. Ravi Kumar: So this is a real, but uncommon example of how the same supplement can carry a very different risk profile depending on your ancestry. It shouldn’t be a reason for everyone to be afraid of lipoic acid, because the vast majority of people tolerate it just fine. It is a reason to know your body, to start low on the dosage, and to take any episodes of shaking, sweating, or confusion very seriously, especially if you have East Asian heritage, or a personal or family history of autoimmune diseases. Okay, so if you take one message away from this episode, let it be this. Alpha lipoic acid is not really the antioxidant that the bottle says it is. It is something much more interesting. It is a hormetic molecule, a tiny controlled stress that does not fight your battles for you, but instead pulls the alarm and wakes up your own defenses and your mitochondria. That is why it shines exactly where mitochondria are under the most strain, like the diabetic nerve, the aging body, the inflamed brain, and also why it does very little for young, healthy people who are already metabolically healthy. It is not a magic pill, but it can be very useful in the right situations. And with that said, I wanna say one more thing.
[24:17 –> 25:09] Dr. Ravi Kumar: All these benefits that you see from lipoic acid can likely be gotten from real lifestyle changes. I’m talking about boring free ones, like movement, real food, not bathing your cells in sugar all day. Supplementing with alpha lipoic acid, when it makes sense, should be a small assist on top of a life that is already designed to optimize your biological health. Okay, so that’s the pod, folks. I hope you enjoyed it. If you found this helpful, please do me a favor and share it with someone that you care about. Maybe a parent who’s getting older and wants their energy back, or maybe a friend with diabetes who’s struggling with burning diabetic neuropathy, or maybe someone who’s tired of taking pills without understanding what they actually do. And if you haven’t done it already, please leave me a quick review on Apple Podcasts. It really helps the show grow. Okay, folks. Cheers, and I’ll see you next time.