GAD stands for glutamic acid decarboxylase, and this is a major enzyme in the synthesis of GABA, which is one of the major inhibitory neurotransmitters in the body. I like to explain it to my patients as the off switch for the nervous system. GAD and GABA are mostly present in nerve cells, but interestingly enough, GAD is also found in the pancreas. GABA is stored in the islet beta cells that produce insulin, and it’s been known for a while that because of this, antibodies to GAD are a predictor of risk and progression to the autoimmune form of diabetes.
In this episode, we cover:
3:08 What Chris ate today
5:48 What are GAD65 antibodies?
9:17 The predictive value of GAD antibodies
18:03 What to do if you produce antibodies
Steve Wright: Good morning, good afternoon, or good evening. You are listening to the Revolution Health Radio Show. I’m your host, Steve Wright, co-author at SCDlifestyle.com.
If you’re struggling with digestive issues, poor sleep, high stress, maybe some mood swings or energy issues, or even chronic nasal congestion, I want to let you know that Chris has put together a program that’s just for you. It’s called 14Four.me. What this is is a 14-day healthy lifestyle reset program. It’s for someone like you who’s dealing with those issues, who wants to do the different pieces that Chris talks about that go into great health. I’m talking about diet, sleep, movement, and stress. Now, trying to tackle all these issues one at a time can be daunting, and so Chris has put them together in a step-by-step, hand-holding formula, where you can basically build these habits into your daily lifestyle. It’s really helpful when starting healthy lifestyle habits that you have a program to follow, so that’s what Chris did when he created 14Four.me. If you haven’t checked it out yet, I would highly encourage it.
With me is integrative medical practitioner, healthy skeptic, and New York Times bestselling author, Chris Kresser. Chris, how’s your day going?
Chris Kresser: It’s going pretty good, especially because you sound like a big-shot radio host over there!
Steve Wright: Well, you know, who knows? We could go on from here.
Chris Kresser: Yeah, we made some big changes in our audio setup. We’re trying to get closer and closer to broadcast quality. I think we’re nearly there. The last methylation podcast with Amy was on the new equipment, and now we have Steve set up, so hopefully you’re enjoying it, all you listeners out there.
Steve Wright: Yeah, leave us some feedback. Let us know what’s working and what’s not working, but I have to say I think I’m sounding a little better.
Chris Kresser: I think you are, too. These are the same mics used on much bigger radio shows like Radiolab and This American Life. I’ve been working with this guy who has just been so generous with his time and helping us to get this all set up, and I’ve learned a lot in the process! So yeah, hopefully you’re enjoying it.
Steve Wright: Awesome. Well, before we get into today’s podcast question — and for listeners, if you’d like your question answered by Chris, make sure you go to ChrisKresser.com/PodcastQuestion and submit it there — but before we actually get into today’s question, Chris, people are dying to know, as always, what have you been eating all day?
What Chris Ate Today
Chris Kresser: Let’s see. For breakfast, we had scrambled eggs, sauerkraut, and sweet potato hash browns. And for lunch, I had some leftover ground beef with some leftover pressure-cooked-in-broth collard greens and a little bit of mashed yuca.
Steve Wright: Nice.
Chris Kresser: With butter.
Steve Wright: How do you make that mashed yuca?
Chris Kresser: You cut the yuca into quarters, and then you try to get the hard kind of thread that goes through the whole thing, and you take that out. You don’t need to. You can mash it and get it out later. Then you cut them into chunks. Then you boil it for at least 20 to 25 minutes, and that’s important to reduce the toxin load because raw yuca, cassava, or manioc, as it’s known, is toxic and goitrogenic, and so you need to boil it first. And of course, you need to boil it to mash it, too. So then you boil it and you drain it and you mash it, and you can add ghee or butter or something like that. There’s a recipe on my website called yuca al mojo, I think, and that will give you the details on how to do it. Yuca con mojo, I think. It’s a Cuban recipe.
Steve Wright: Awesome. And for those of us who love bacon, you can just put bacon in there, too, probably.
Chris Kresser: Yeah. The mojo is not so much of a mashed one. It’s usually chunks, but it’s soft and you can mash it from there if you want.
Steve Wright: Awesome. Well, let’s roll on to today’s question.
Chris Kresser: Great. Yeah, this question is from Ruth. Let’s give it a listen.
Question from Ruth: Hi, Chris. My question is about autoimmune type 1 diabetes. I’m wanting to know if someone’s presenting with elevated GAD65 antibodies — so developing the disease — is there anything, in your opinion, that can be done to reverse or stop the progression to full-on type 1 diabetes? I find it really frustrating that there’s so much information about type 2 diabetes and reversing type 2, and I just wondered whether there was anything that could be done for type 1 diabetes. Thank you.
What Are GAD65 Antibodies?
Chris Kresser: OK. Well, thanks, Ruth, for sending us that question. Let’s start by talking a little bit about what GAD65 antibodies are. GAD stands for glutamic acid decarboxylase, and this is a major enzyme in the synthesis of GABA, which is one of the major inhibitory neurotransmitters in the body. I like to explain it to my patients as the off switch for the nervous system. GAD and GABA are mostly present in nerve cells, but interestingly enough, GAD is also found in the pancreas. GABA is stored in the islet beta cells that produce insulin, and it’s been known for a while that because of this, antibodies to GAD are a predictor of risk and progression to the autoimmune form of diabetes. In autoimmune diabetes, the body attacks insulin-producing cells or even insulin itself in some cases, which then leads to insulin deficiency, and that’s why people with type 1 diabetes or type 1.5 diabetes, which we’re going to talk about in a second, end up needing to take insulin in many cases because their body is not producing the appropriate amount of insulin because of this autoimmune attack.
Insulin deficiency, of course, can also occur in the later stages of type 2 diabetes, which is not autoimmune. In that case, it happens as a result of inflammation and metabolic changes that eventually lead to a destruction of the beta cells that produce insulin. And so in the very kind of end stage of type 2 diabetes, patients will often require insulin, but that’s not typically from an autoimmune cause. Type 1 diabetes, which is usually juvenile onset and appears during childhood, is autoimmune, and that involves, as I just said, the body attacking the insulin-producing cells, and you get an insulin deficiency and have to take insulin as a result. But there’s another type of diabetes that has been referred to as type 1.5 because it kind of has characteristics of both type 1 and type 2 diabetes. Another term for it is latent autoimmune diabetes in adults, or LADA. What happens here is it’s an adult onset of autoimmune diabetes. So rather than coming on in childhood like type 1 diabetes does, it comes on later in life and has many of the same characteristics of type 1 diabetes in that it’s an autoimmune condition and it leads to destruction of the beta cells and a reduction in the production of insulin.
Steve Wright: So the only difference between 1 and 1.5 is just the time in which it strikes or becomes activated?
Chris Kresser: There are some other differences as well, and there’s some heterogeneity in terms of how it manifests, so it doesn’t always look the same. Some people are kind of closer to the type 2 presentation, and other people are closer to the type 1 presentation, but yeah, that’s the gist of it. Typically type 1 diabetes has been strictly juvenile onset, but type 1.5 is adult onset.
What Is the Predictive Value of GAD Antibodies?
The important question here is, what is the predictive value of GAD antibodies? If somebody does a test and it comes back positive for GAD antibodies, how much does that tell us about the likelihood that they will go on to develop type 1.5 diabetes or type 1 if they’re getting this test when they’re a child? Well, it turns out that GAD antibodies, even by themselves, do have moderate predictive value, but when you combine them with other antibodies like islet antigens insulin, or IAA, or IA-2 antibodies or zinc transporter antibodies, the predictive value goes up significantly. For example, some models show that having three positive antibodies implies a risk of between about 50% and 85% over five years that the patient will develop the clinical signs of type 1.5 diabetes or 65% to 85% chance over 10 years. So with three positive antibodies, that’s a relatively high chance that within 10 years you would develop the clinical signs of type 1.5 diabetes. However, there are a few studies that put it even higher than that. I saw one model that estimated that 100% of people with three positive antibodies will go on to develop the onset of autoimmune diabetes within five years. So, one antibody appears to be moderately predictive. With three antibodies, the risk is anywhere between 50% and 100% in five years, depending on what study you look at.
However, — and I think this is a relatively big however — we have to remember who the population is that is studied. In these studies where they’re looking at people who test positive for the antibodies and then following them over a course of time and checking to see if they develop the clinical signs of diabetes, this is typically an industrial population either in the US or Europe. They are people that are probably overall eating a pretty crappy diet because we know that that’s the default for most people in the industrialized world. They’re probably not getting enough exercise. They’re probably not getting enough sleep. They’re not taking care of themselves in the same way that, hopefully, all of you who are listening to this show are. We know that those kinds of environmental factors play a very strong role in the onset and progression of autoimmune disease, so for me, it stands to reason that the predictive value of these antibodies may be lower in a population of people where they’re really taking care of themselves and following all the best practices that we talk about on this show and I write about on the blog. Unfortunately, we don’t have any data on that. It would be great if we had a prospective study of people with these antibodies who were eating a paleo type of diet and living a paleo type of lifestyle and were followed for 10 years, but we don’t have that study, and we’re not likely to anytime soon.
Steve Wright: Now, are these antibodies all related to the pancreas or beta cells? Because you mentioned many of them.
Chris Kresser: Yeah, they’re all related to the pancreas or insulin-producing cells. As I mentioned earlier, some much smaller number of people actually produce antibodies to insulin itself. That’s much less common. But all these antibodies relate to the production of insulin or that system. GAD is also found in other places, though, like the brain. GAD antibodies are not exclusive to the pancreas or the function of the pancreas. As I mentioned before, GAD is present mostly in nerve cells and the central nervous system and the brain, but in this case, they are often a marker of potential for type 1.5 diabetes or type 1 diabetes, especially in the presence of these other antibodies.
Steve Wright: I’m no diabetes expert, but I’ve never heard of some of these. How often are these ever done in a clinical setting?
Chris Kresser: It’s getting more common, but you’re right; you’re not going to find them on your typical blood panel with your primary care doctor. GAD antibodies are part of the Cyrex Array 5, which is their multiple autoimmune reactivity panel, where they screen for antibodies to a number of different tissues. And the reason that panel can be a good idea in some cases is just for the reasons that we’re discussing. The production of antibodies to a particular tissue usually precedes the development of disease in that tissue or system by several years and even up to a decade or more. So if you identify the production of antibodies early on, then you have a much better chance of intervening and preventing the development of disease as you go.
Now, there’s unfortunately very little research on whether onset can be prevented because this isn’t really the specialty of conventional medicine, as we all know, i.e. prevention. Conventional medicine is much better at intervening at the far other side of the disease spectrum, when disease has already manifested and become quite severe. I really would love to see more research on, like I mentioned before, studying people who are really taking care of themselves and determining what changes people can make to prevent the onset. What we have now is just theories, and I think there are theories that are based on evidence and research, and we’re going to talk about some of those suggestions shortly, but we don’t know with 100% certainty. We can’t make any guarantees.
Steve Wright: And just for listeners, Chris, I don’t know if most people understand the difference between having an actual disease diagnosis and the level of destruction that happens from the initial onset of the ability to detect that there is some autoimmune activity. Could you just really quickly go over that?
Chris Kresser: Yeah, that’s a good question. Autoimmunity means the production of antibodies to a particular tissue. Autoimmune disease refers to a disease state that is a result of autoimmunity, a result of the production of those antibodies. You can have autoimmunity without having autoimmune disease. An example would be with Hashimoto’s, which is the autoimmune disease that is caused by production of antibodies to the thyroid or tissues in the thyroid. Only about — well, I say ‘only.’ This may sound high or low to you. I’m not sure. It’s not true that everyone that produces antibodies to their thyroid will go on to develop clinical hypothyroidism. In fact, I think in most of the papers I’ve seen, it’s between 20% and 30% of people who develop antibodies will actually ever go on to have hypothyroidism. That tells us that the production of antibodies to tissue doesn’t always lead to frank tissue destruction to a level that would cause clinical disease. It’s important to understand that distinction because it means that if you intervene early enough, you may be able to arrest the progression from just the mere production of antibodies to the destruction of that tissue that the antibodies are tagging.
What to Do If You Produce Antibodies
Let’s talk a little bit about what I would recommend in this situation if you see that you’re producing antibodies to a particular tissue, because although we don’t have proof that this will arrest the development of autoimmune disease, there is a lot of research that suggests that autoimmunity is triggered or exacerbated by a whole bunch of different factors, like intestinal permeability and poor nutrition, lack of exercise, inadequate stress management, lack of sleep or poor quality sleep, environmental toxins. I just read a really fascinating study, for example, showing that people with mercury amalgams who had positive thyroid antibodies, when they took out their mercury amalgams, their thyroid antibodies went down significantly just from removing the mercury from their mouth. And then there are chronic infections and a whole bunch of other influences. So there are a lot of things in our environment that we’re exposed to that can trigger or exacerbate autoimmunity and autoimmune disease, so in our work with patients, this is what we focus on. These are things we’ve talked about a lot, so I’m not going to go into detail on each category. I’m just going to give you some of the things to focus on, and then if you need more detail, you can check out the book and other podcast episodes and the blog, of course, and the free eBooks we have on the site.
In terms of diet, of course, you want to focus on a nutrient-dense paleo type of diet, but you might also want to consider an autoimmune protocol, especially if you think you have sensitivity to things like nightshades or eggs or dairy products. You may want to consider something like the Wahls protocol, which was developed by Dr. Terry Wahls for her in her own experience dealing with MS, autoimmune disease, a pretty miraculous response for her. It took her from being in a wheelchair to being able to walk and speak. I just saw her at Paleo f(x) a couple of weekends ago, and she was presenting there, as she often does. Pretty incredible results just by switching to a nutrient-dense, low-toxin, anti-inflammatory diet.
You’d probably want to test for food intolerances using something like Cyrex Array 3 or Cyrex Array 4. They have a new screen, Array 10, and we’ve been using it a little bit, but the jury is still out for me on that test and its value. Maybe we can talk about that a little more.
Steve Wright: Does that mean that the jury has come to a decision or at least a quasi-decision with regards to Array 3 and 4 with Cyrex food sensitivities? Because we’ve talked about those in the past.
Chris Kresser: Yeah, well, my feeling about those, I think Cyrex Array 3 is pretty reliable and accurate in terms of gluten sensitivity, and generally most foods that contain gluten don’t really have a ton of nutritional value anyway, and they’re not something that I think people should be really focusing on in their diet even if they aren’t gluten intolerant. The downside of removing gluten from your diet is not that big, and I think it’s the most advanced test for gluten intolerance out there, and we use it. I like it.
Array 4 is looking at cross-reactivity to other proteins, like eggs and dairy and other kind of alternative grains, non-gluten grains and things like yeast and coffee. There’s a whole debate about whether cross-reactivity even exists. I don’t want to go into that now, but I’ll just say that we use Array 4 as kind of a springboard for elimination/provocation testing. In other words, if someone tests positive for eggs, we won’t tell them, OK, that’s it. You have to avoid eggs for the rest of your life, no matter what. We’ll say, OK, let’s test this out. Avoid eggs for 60 days, 30 days. Add them back in and see if you notice any symptoms or if we see any changes in your labs, and if we do, well, then you probably should avoid them. If we don’t then I’m not convinced that they will need to avoid them, especially after we address the underlying issues. And that’s kind of how we’re using Array 10 as well as this point. If it comes back and says, OK, raw strawberries are off the menu. Well, let’s test that out before you completely avoid that food for the rest of your life. I think that’s generally how this testing should be used.
Gut health, of course, is another huge concern with autoimmunity. People like Dr. Alessio Fasano believe that leaky gut is a precondition to developing autoimmune disease in the first place, so getting tested for SIBO, gut infections and inflammation, intestinal permeability, emphasizing gut-healing foods, eating plenty of fermentable fibers and fermented foods and maybe even using commercial prebiotics and probiotics are all something to consider. And you can check out my free eBook on gut health at ChrisKresser.com to get started if you’re new to that.
Stress management. This is something we’re always talking about, but it can really not be emphasized enough. It’s crucial for immune health, and unfortunately it’s often overlooked. There are so many studies that show that the onset of autoimmune disease is associated with stress. We live, many of us, in a pretty stressful environment, so this is something that people really struggle with, but it’s really important to take some steps. 14Four, of course, that was one of the main reasons I did that program, was to give people some resources and tools to help them get started with these kinds of things.
The same is true for sleep. It’s crucial for immune regulation. Thirty percent of Americans are sleeping fewer than 6 hours a night, and most of us need 7 to 8 hours to function properly.
And physical activity. Not just getting enough exercise, but sitting less. Not sitting for hours and hours every day. Punctuating that sitting, if you have to sit, with frequent breaks, walking more, doing some high-intensity activity, and avoiding overtraining.
Again, 14Four is an excellent option. If you’re new to this and you want to nail your diet, stress management, sleep, physical activity, and even gut health, that will get you on the right track.
Finally, supporting T regulatory cell function. T regulatory cells, or Tregs as they’re often called, play a very important role in balancing and regulating the immune system. There are a number of things that you can do to support the Tregs, including normalizing your vitamin D levels, making sure they’re in the right range, boosting your glutathione levels through a nutrient-dense diet and supplementation, increasing your butyrate levels, which is a short-chain fatty acid that promotes T regulatory cell function and reduces inflammation. Things like curcumin, particularly bioavailable forms, like a liposomal curcumin, that’s anti-inflammatory and promotes T regulatory cell function.
And then if you have maybe all three of the antibodies, which would suggest a very high likelihood of developing autoimmune diabetes, you might consider something like low-dose naltrexone as a prophylactic. We did a show on low-dose naltrexone not too long ago, so you could give that a listen and talk to your doctor about it.
All right, Steve, that’s it for this episode. I hope it was helpful, and we’ll see everybody in a couple of weeks.
Steve Wright: Yeah, I appreciate it, Chris, appreciate all the research that you do. I know the listeners do, as well. For everybody who’s listening and you’re wondering what Chris is researching, what articles he’s reading, things that might not make it onto the RHR Show or onto his blog, he publishes all that stuff on social media. So if you haven’t yet, go to Facebook.com/ChrisKresserLAc and give him a follow and Twitter.com/ChrisKresser. Thanks for listening, and as we mentioned before, this podcast is created for you and also by you, so go to ChrisKresser.com/PodcastQuestion to submit your questions.