Find out what the latest research has shown in terms of the pathogenesis and etiology of Parkinson’s. What are some of the predisposing factors? What are some of the things to look out for that can be causative? And what kind of clues might those things give us in terms of treatment?
Parkinson’s is obviously a neurological, neurodegenerative condition. If you’ve been following my work, listening to this show for any length of time, you’ll know that I spend a lot of time thinking and talking about the gut-brain axis. Whenever we talk about any kind of brain condition, we always have to look at the gut. And vice versa. If we’re talking about gut condition, we have to look at the health of the brain. That’s because the gut and the brain exists in this axis that’s interrelated and bidirectional. So the gut affects the brain and the brain affects the gut. This can give us, again, some clues in terms of what to look for whenever we’re dealing with a condition that manifests anywhere on this axis. It turns out there is actually a lot of research, most of it fairly recent, that makes a strong connection between gut dysfunction and Parkinson’s.
In this episode, we cover:
6:25 The latest Parkinson’s research and what to look for
13:34 Is Parkinson’s an autoimmune condition?
23:22 Parkinson’s treatment
Steve Wright: Good morning, good afternoon, and good evening. You are listening to the Revolution Health Radio show. I’m your host, Steve Wright, co-author at SCDlifestyle.com. This episode of RHR is brought to you by 14Four.me. Now if you haven’t heard of this 14-day healthy lifestyle reset program that Chris has put together, you’ll want to listen in for a little bit here. This program is really meant for somebody who’s still struggling with their digestion, maybe they’re struggling with acne, maybe a little weight gain, or any one of these nagging lifestyle symptoms. 14Four is the program for you. Basically, it’s 14 days with four different areas of focus. That includes diet, sleep, stress, and movement. If you listen to this show at all, you know that these are very important topics for your overall well-being, from recovering from weight gain to leading a healthy lifestyle. The problem typically is actually implementing them in your life and doing them all at the same time. So that’s what 14Four does. I urge you to go check it out at 14Four.me. With that said, with me is integrative medical practitioner, healthy skeptic, and New York Times bestselling author, Chris Kresser. Chris, how’s your day?
Chris Kresser: It’s great. It’s beautiful, cloudless sky here in California. It’s a little chilly, but a gorgeous day. How about you?
Steve Wright: My day is going great. It’s a ridiculous snowstorm out there, but I got my new tea kettle right here.
Chris Kresser: Oh, very nice. It’s very nice. I like it. I’m having some kukicha, or twig tea, at the moment.
Steve Wright: Oh my gosh. I was about to brag about my blend of turmeric and yerba mate, but you just stole the show, man.
Chris Kresser: No, no. Twig tea is green tea. Most green tea comes from the leaves of the plant, but this is from the stem or the twigs. It’s a lot lower in caffeine. It has kind of an earthier flavor. It’s one of my preferred afternoon beverages because it doesn’t jack me up like stronger caffeine would, but it gives me a nice little lift.
Steve Wright: I didn’t even know there was such a thing as twig tea. See? That’s why I love doing this show.
Chris Kresser: You learn something every day. And I’ve got my favorite new cup. Can you see it?
Steve Wright: Oh, I see it! Is that a Christmas gift?
Chris Kresser: I made it as Christmas gifts for other people, and I had to give myself one too. Other people in my family. So pictures of Sylvie all around the cup.
Steve Wright: Sylvie has officially made the show.
Chris Kresser: Yeah, she has. We have a good show planned today. It’s a question about Parkinson’s disease, which is a—there’s some really interesting new research coming out. It’s a tricky disorder to work with, no doubt. It sounds like Anthony’s doing a lot of the right things, which we’ll hear about in a second. But I’m going to give him and the rest of the listeners hopefully some new ideas for some things to focus on, and just kind of summarize some of what the latest research is telling us. Let’s hear from Anthony. We’ll go from there.
Anthony: Hi, Chris. This is Anthony DiClementi from Chicago. I’m a big fan of your show. Thank you for doing what you’re doing. Please keep it up. My question is this. It’s actually about my dad. My father has been experiencing some Parkinsonian symptoms now for the past few years. His mother is in the process of passing away after dealing with Parkinson’s herself. We have done a number of interventions that have helped, ranging from introducing the ubiquinol form of CoQ10 at 300 mg/day. We’ve also gotten him doing B12 shots, taking the bioactive form of folate and B6, along with some B12 lozenges and omega-3 supplements, and some other things that we found to be helpful. He’s also taking acetyl-L-carnitine, the Memory Pro product. Some of that has helped. It’s slowed the progression, but it hasn’t necessarily reversed things. He was always a really strong guy. The past five or ten years, he’s experienced a very steep physical and cognitive decline. My question is, what protocol do you use with your patients that are expressing Parkinsonian-like symptoms when haven’t yet been diagnosed with Parkinson’s? Because you want to try to intervene before it progresses to that point. Is there a way that you could recommend us finding a good physician to help with this in the Chicagoland area? Thank you so much for your time. I really appreciate this. We’ve really tried to do everything we can in our power from a dietary and supplemental perspective. We’ve decreased his protein intake significantly, trying to get him to eat more vegetables. Then we’ve got him on those supplements that I mentioned plus some more. But anything you can share would be very, very helpful, particularly in terms of the protocol that you use and finding a good physician for us to work with. Thank you so much, Chris. I really appreciate it.
Steve Wright: Before Chris gets into this, if you want to be Anthony, if you would like advice like this from Chris on your situation or what you’re doing, make sure you go to ChrisKresser.com/podcastquestion. This radio show is brought to you by you and for you, so make sure you do that. All right, Chris. Take it away.
Chris Kresser: All right. As I mentioned, a lot of the things that Anthony and his family are doing are definitely good ideas and things that can be really helpful. I’m just going to mention a few other things. I’m going to talk a little bit more about what the latest research has shown in terms of the pathogenesis and etiology of Parkinson’s. In other words, what are some of the predisposing factors? What are some of the things to look out for that can be causative? And what kind of clues might those things give us in terms of treatment?
The latest Parkinson’s research and what to look for
Parkinson’s is obviously a neurological, neurodegenerative condition. If you’ve been following my work, listening to this show for any length of time, you’ll know that I spend a lot of time thinking and talking about the gut-brain axis. Whenever we talk about any kind of brain condition, we always have to look at the gut. And vice versa. If we’re talking about gut condition, we have to look at the health of the brain. That’s because the gut and the brain exists in this axis that’s interrelated and bidirectional. So the gut affects the brain and the brain affects the gut. This can give us, again, some clues in terms of what to look for whenever we’re dealing with a condition that manifests anywhere on this axis. It turns out there is actually a lot of research, most of it fairly recent, that makes a strong connection between gut dysfunction and Parkinson’s. For example, constipation has been shown to precede the development of the somatic motor symptoms of Parkinson’s disease for several years. We have studies showing that the intestinal microbiome, the gut flora, is altered in Parkinson’s disease and is directly related to motor phenotype. So the specific kind of type of microbiome presentation relates to the different ways that Parkinson’s manifests. We know that the abundance of particular phyla of bacteria in the stool of Parkinson’s patients—we see an abundance of certain types of bacteria, rather, in the stool of Parkinson’s patients versus controls. There is even some experimental evidence in animals that altering the balance of these bacteria can have an effect in terms of treatment. We know that Parkinson’s patients have significantly greater intestinal permeability, i.e. their guts are more leaky than patients without Parkinson’s. We know that intestinal permeability in Parkinson’s patients is correlated with markers of oxidative stress and endotoxin exposure, like exposure to lipopolysaccharide.
Finally, there’s quite a lot of research correlating Parkinson’s with small intestinal bacterial overgrowth (SIBO). I’ve mentioned this before, but one study detected SIBO in 25% of Parkinson’s patients. Another study found even higher prevalence of SIBO in Parkinson’s disease versus controls. So 55% of the patients with Parkinson’s had SIBO versus 20% of controls, which is, by the way, a pretty high percentage for controls. Another study found an even bigger difference. It was 54% in Parkinson’s with SIBO versus just 8% of controls. And Parkinson’s patients with SIBO have much worse motor function than Parkinson’s patients without it. We know that eradication of SIBO in Parkinson’s patients results in an improvement in motor function. And for some reason, probably related to motility via the gut-brain axis and the vagus nerve, the relapse rate of small intestinal bacterial overgrowth in Parkinson’s patients is unfortunately very high. It’s 44% even at just six months after treatment. The relapse rate for SIBO in general is quite high, but it’s even higher for Parkinson’s patients. That probably is because of that bidirectional connection between the gut and the brain. In other words, SIBO is making Parkinson’s worse or contributing to Parkinson’s, but Parkinson’s is probably contributing to SIBO as well via perhaps a reduction in gut motility. So when you put all that together, it’s a pretty strong relationship between digestive and gut function and the risk of developing Parkinson’s disease, and also just exacerbating it if it’s already present.
Steve Wright: That’s just another reason why I want to keep pooping on a daily basis. I did not know that connection.
Chris Kresser: Yeah, one of many reasons. This show, we can almost sound like a broken record sometimes, because just about any condition that we talk about at this point has a strong correlation to gut health, you know, the gut microbiota, the intestinal barrier, and SIBO. And really, that’s good news. Because from a functional medicine perspective, we’re always—you know, a patient might walk through my door. Let’s say two different patients. They might have very different symptoms. But as a functional medicine practitioner, I know that I need to be really looking at the same basic systems for most patients. Like, I’m looking at the gut, I’m looking at the HPA axis, I’m looking at oxygen deliverability and blood sugar regulation, I’m looking at methylation. These are all the underlying mechanisms that tend to be at the root of most modern disease, regardless of whether we’re talking about diabetes, cardiovascular disease, autoimmunity or neurodegenerative conditions like Parkinson’s and Alzheimer’s. So it actually really simplifies things in a way, if you’re approaching things from a functional medicine perspective.
One more aspect of gut health, but also just immune function that’s linked to Parkinson’s, is gluten intolerance. There’s a fair amount of literature suggesting that gluten intolerance, non-celiac gluten sensitivity, especially when it is connected, when transglutaminase 6 (tTG6) antibodies are present. Transglutaminase 6 is an enzyme that has a lot of activity in the brain. And in patients who are gluten intolerant who also produce antibodies to transglutaminase 6, when they eat gluten, their body essentially attacks this transglutaminase 6 enzyme in the brain and causes neurodegeneration. This is present in some patients with Parkinson’s. Gluten, therefore, can contribute to and exacerbate Parkinson’s if a person is gluten intolerant. Cyrex Array 3 is the best test available right now for testing reactions against the full wheat proteome, not just gluten, but other proteins in wheat. They also run antibodies to transglutaminase-2, -3, and -6. So this can be helpful. I don’t think I’ve had a Parkinson’s patient with tTG6 antibodies, but I’ve had certainly a lot of children on the autism spectrum and other people with neurodegenerative, neurological disorders test positive for antibodies to various epitopes of gliadin, agglutinin or wheat germ agglutinin (WGA) and also tTG6. There’s a very close correlation between that and their symptom presentation.
Is Parkinson’s an autoimmune condition?
Steve Wright: Is this a good chance to ask a question? If gluten is causing potential reactions to the brain, is Parkinson’s, in your opinion, an autoimmune condition?
Chris Kresser: Well, it’s interesting that you ask that. I don’t know. It has some characteristics that could be—you know, autoimmunity may play a role. Actually, one of the things I was going to talk about next was low-dose naltrexone (LDN) as a potential therapy for Parkinson’s. I’ll just skip to that now. Because the fact that low-dose naltrexone seems to work in some cases may actually suggest that there is autoimmunity present or autoimmunity may play a role in Parkinson’s. We know that LDN halts progression in some cases of multiple sclerosis, and it’s been used more recently with other neurodegenerative conditions like Parkinson’s and amyotrophic lateral sclerosis (ALS), which is Lou Gehrig’s disease. These conditions are still not that well-understood in terms of their etiology, but there is some evidence that suggests an autoimmune mechanism, which could explain why low-dose naltrexone works.
For those who aren’t familiar with LDN and haven’t heard me talk about it in the past, there are a few mechanisms of action of LDN. One is that it promotes T regulatory cell function. The T regulatory cells are cells that help balance and regulate immune function. That’s why LDN tends to work so well in autoimmunity. But LDN also reduces central nervous system inflammation, and we know that Parkinson’s is characterized by both inflammation and oxidative damage in the central nervous system in the brain. So that’s another reason that LDN might work for Parkinson’s. LDN is also a prokinetic, which means that it increases intestinal motility. It’s being used by people who are on the front line of SIBO treatment, like Dr. Mark Pimentel at Cedars-Sinai, for patients who don’t respond to typical SIBO treatment because their motility is impaired. Or let’s say they do respond, like they get rid of SIBO, but it comes back. They relapse because their motility is slowed down, which means the cleansing peristaltic wave doesn’t happen, which means they’re much more likely to get bacterial overgrowth in the first place. LDN is being used as a prokinetic to promote better motility and reduce the chances of relapse for SIBO therapy. And because, as I mentioned, Parkinson’s is related to SIBO, and Parkinson’s patients have a high probability of relapsing for SIBO, then LDN could be effectively used as a prokinetic in Parkinson’s treatment.
There’s a researcher, Dr. Hong at the National Institutes of Health, who believes that Parkinson’s and MS are caused by overactivated microglial cells, which are the immune cells, killer cells in the brain, which in turn, causes chronic brain inflammation. And we have evidence that low-dose naltrexone (LDN) significantly inhibits brain inflammation, neuroinflammation. So I wouldn’t call Parkinson’s like a straight up autoimmune disease in the way that we understand other autoimmune diseases like MS and celiac, but I would say that there is enough evidence that it does have some characteristics of autoimmunity, and may respond therefore to some of the same kinds of dietary, supplement, and perhaps medication and lifestyle interventions that autoimmune disease responds to.
So there’s another whole piece here to look at in terms of etiology and treatment. It’s iron overload. I’ve spoken a lot about this in the past. In fact, I gave a talk on iron overload at the Ancestral Health Symposium. I think it was 2012 or 2013, I can’t recall. The talk is available online for free. I think if you search for “Chris Kresser iron overload”, you’ll find it. What I argued in that talk is that there’s a lot of evidence that high-normal and just slightly elevated iron levels, which are completely ignored in the conventional medical establishment, can actually be a pretty serious risk factor for a number of different diseases, including things like Parkinson’s disease. We know that iron is a catalyst of oxidative damage. It’s a free radical, so it causes oxidative stress and inflammation. You know, all of the tissues in the body are sensitive to that, but some of the tissues that are the most sensitive would include the liver, the heart, the pancreas, and, of course, the brain and the small organs in the brain. So iron has been strongly implicated in several neurodegenerative disorders, including Parkinson’s disease.
I read a paper not too long ago that went as far as saying that the underlying pathogenic event in oxidative stress in the brain is cellular iron mismanagement. I test everyone who comes into my practice for iron—you know, they get a full iron panel. We’re testing for iron deficiency and for iron overload. In my patient population at least, who is typically on a Paleo diet, eating red meat and a lot of other iron-rich foods, iron deficiency is actually fairly rare. Worldwide, iron deficiency is a huge problem. Two billion people around the world suffer from it. If you were to look at the general population in the US, you’d find that iron deficiency is a much bigger problem than iron overload, especially in women. But in my patient population, iron overload is actually fairly common.
So one of the things that you want to look for, especially if you’re a man, is iron overload. You would be looking at markers like serum iron, iron saturation, total iron-binding capacity (TIBC) and unsaturated iron-binding capacity (UIBC), and ferritin as a starting place. If those numbers are indicative of iron overload, then you’ll want to look into an iron reduction protocol, which could include things like blood donation. That’s phlebotomy. Removal of blood is the most effective way of reducing your iron levels. Reducing your consumption of the most iron-rich foods, which unfortunately are some of the healthiest foods to eat, like organ meats and shellfish. You want to avoid high doses of vitamin C and HCL because they both significantly increase iron absorption. Bad news here: alcohol also significantly increases iron absorption. So sitting down to a meal of liver and onions with a glass of wine and taking some HCL capsules and vitamin C beforehand would definitely not be a good idea if you have iron overload.
Steve Wright: What if you’re strapped to a table and you’re currently bloodletting? Is it okay then?
Chris Kresser: Right. Then you should make sure to cook that meal in a cast iron skillet that’s really old and visibly flaking off before you do that. Yeah. Definitely check out that presentation if you’re curious about this, because there’s a lot more detail in there about how to approach this. We don’t have time to go into it today, but that’s definitely something you want to consider. The reason I said it’s more of an issue in men is that—and postmenopausal women, I should say—premenopausal women, women who are still menstruating, lose a little bit of iron each month in the menses. They’re a lot less likely to develop iron overload in the first place. But men, obviously that’s not happening. We just accumulate iron as we go through our lifetime. In most cases, we have a very intelligent mechanism for storing the appropriate amount of iron. Let’s say I eat liver. The cells in the intestine and other signaling cells or signaling molecules will kind of check in with my body and see how much iron I have stored. If I’ve got enough iron, then I just won’t absorb any of the iron from the liver; I’ll just excrete it. But there are a lot of different genetic mutations that can interfere with that iron-sensing function, and some people just go on absorbing more iron even if they have enough stored. Those are the people who are likely to develop iron overload. So it is more common in men. But when women enter menopause and stop the monthly menstruation, the rate of iron overload starts to equalize with men and postmenopausal women.
Steve Wright: This is just a side tangent. If people still can’t figure out how to get their liver, like the people who don’t have iron overload, for those of you who still can’t figure out liver consumption, EPIC Bar—I don’t know if you saw this, Chris—just came out with a liver beef bar.
Chris Kresser: Awesome.
Steve Wright: As far as I can tell, after several taste testings with myself and other people, it tastes better than all the other EPIC bars they’ve made so far. So check that out.
Chris Kresser: Cool. No, I didn’t know that. That’s a good tangent. Anything that can help people eat liver is always a good tangent. Let’s see.
A couple more things I want to cover before we finish, in terms of potential things to try. Curcumin is a compound that’s found in turmeric in the diet. It protects against inflammation and oxidative damage. It crosses the blood-brain barrier and is neuroprotective in several different neurological disorders. It’s really quite remarkable in its effects on a lot of different brain disorders. However, most oral forms of curcumin are poorly absorbed. If you eat a lot of turmeric, it might taste good if you like turmeric or if you drink it in your tea like Steve’s doing. It’s definitely a great thing to do, but you’re not going to absorb huge amounts of bioavailable curcuminoids, which are the active compounds. There have been a number of forms that have been introduced in recent years that have much better absorption. Things like the BCM-95 form, Theracurmin, the Longvida form, and then most recently, liposomal forms of curcumin. I think liposomal delivery is probably the best for a lot of these nutrients that can be difficult to absorb. We’ve been using liposomal curcumin more in our practice recently. I’ve seen some pretty good results. I’ve taken it myself, along with other forms of curcumin. I think the liposomal form probably works best. That’s something to consider.
Steve Wright: Do you have a brand there?
Chris Kresser: The Seeking Health brand is pretty good for liposomal curcumin. Then Longvida, L-O-N-G-V-I-D-A. It’s not a brand. It’s a patented form or delivery system. A lot of different supplement brands use Longvida. You can just search for Longvida. They have their own website. Then on the Longvida site, it shows what different brands contain the Longvida form. That’s one way to do it too. The last thing is the ketogenic diet. You know, I recently wrote a whole series about carbs and the pros and cons of low-carb diets. In one of the posts, we talked about when very low-carb diets are appropriate and effective. One of those situations was, of course, neurodegenerative conditions, which we’ve talked about before. Ketone bodies that we produce, if you’re on a ketogenic diet, bypass defects in mitochondrial complex I activity. These defects in mitochondrial complex I have been implicated in Parkinson’s disease. So ketone bodies can bypass that and promote more normal cellular metabolism. There’s very little research in actual human beings on the effects of ketogenic diet on Parkinson’s. But there is a very small study, with only seven patients, that showed that 28 days of ketogenic diet improved Parkinson’s, as measured by a disease rating scale that’s often used to subjectively determine disease activity.
Then we have some animal and in vitro studies that have shown benefits with a ketogenic diet. But of course, we need more research ideally to really show that this is effective. However, it’s a safe thing to try I think if it’s done responsibly, especially compared to some other drugs. And if you put together an approach that includes testing for and then treating any gut issues, like SIBO or intestinal permeability or dysbiosis, if you test for gluten intolerance and remove gluten from the diet, if you test for iron overload and then get iron levels back to normal, if you consider perhaps low-dose naltrexone as a way of reducing CNS inflammation and promoting T regulatory cell function, if you use something like liposomal curcumin to reduce oxidative damage and neuroinflammation, and then you try a period of time on a ketogenic diet, I think that could be a pretty effective strategy altogether. All of it is relatively low risk in terms of side effects and potential complications, compared to some of the drug treatments that are available. I hope this was helpful, Anthony, and gives you some ideas to focus on. I hope for those others that are listening, who have a family member or a friend who’s affected by Parkinson’s, this gives you some things to think about.
Steve Wright: I think it’s an amazing approach you just laid out there, Chris. I hope this really helps Anthony. One question. I know we’re out of time here, but I feel like it’s worth asking for people out there. What about some S-acetyl glutathione or some intravenous glutathione in a case like this?
Chris Kresser: Great question. Maybe I misread the question. I thought he had mentioned glutathione, but it’s possible that he didn’t. Glutathione would definitely be helpful. Glutathione and curcumin together can be really effective, a kind of one-two punch in terms of addressing oxidative stress and inflammation. Glutathione, of course, is the master antioxidant in the cells. We know that glutathione is depleted in several different conditions, like autoimmune diseases. It’s also depleted by numerous aspects of the modern lifestyle, like not sleeping enough, stress, not exercising enough, and poor diet of course. That’s because a lot of the precursors of glutathione, we know, especially from the recent NHANES Nurses’ Health Study data that just came out, that almost half of the population is deficient in most of the antioxidant vitamins, like vitamin A, vitamin C, vitamin D, and vitamin E. When I test people for glutathione status, it’s extremely common to see markers for both a high need and demand for glutathione, and also inadequate intracellular levels of glutathione. So yeah, liposomal glutathione, again, is probably my favorite way of taking glutathione. But you can also use precursors like alpha-lipoic acid and N-acetylcysteine. Whey protein is a good precursor for glutathione, if you tolerate that. Fresh fruits and vegetables in the raw form are a good source of glutathione as well. Exercise upregulates glutathione production. Stress reduction is important for glutathione. Great question, Steve.
Steve Wright: Thanks. I can’t remember if Anthony mentioned it or not, but I felt like that was a good thing to add in there.
Chris Kresser: It’s important. You’re right.
Steve Wright: All right.
Chris Kresser: That’s it.
Steve Wright: Thanks, everybody, for listening to this show. Like I mentioned earlier, go to ChrisKresser.com/podcastquestion to get help for you or your loved ones on the show. In-between episodes, if you’re wondering—for instance, I didn’t know about this new Nurses’ Health Study that Chris just mentioned. It’s probably because I don’t check Facebook enough, and when I’m on Facebook, I don’t go to Facebook.com/ChrisKresserLAc enough to see what Chris is reading and the new studies that are coming out. If you’re on social media, whether you’re a Twitter or a Facebook person, make sure you check him out in either place. Twitter.com/ChrisKresser. Thanks, Chris.
Chris Kresser: Thanks, Steve. Thanks, everyone. See you next time.