Nutritional Approaches for Parkinson’s Disease with Dr. Heather Zwickey

Dr. Zwickey is the dean of research and graduate studies at the National University of Natural Medicine (NUNM), director of Helfgott Research Institute, and professor of immunology. In 2003, Dr. Zwickey launched the Helfgott Research Institute at NUNM, where she applies her immunology expertise to natural medicine. She studies the immunological mechanisms involved in nutrition, herbal medicine, acupuncture, and mind-body medicine. Her current area of focus is the inflammatory components of Parkinson's disease. Dr. Zwickey has used her expertise in program development to establish the School of Research and Graduate Studies at NCNM, and serves as its leader. She has developed Masters programs in Integrative Medicine Research, Nutrition, and Global Health.

Transcript

Dr. LS Hi, I'm Dr. Liz Sutherland from AARM, the Association for the Advancement of Restorative Medicine. My guest today is Dr. Heather Zwickey. Dr. Zwickey is an immunologist and NIH-funded researcher who teaches nationally and internationally about the effects of nutrition and natural therapies on the immune system. Today, she'll turn her expert lens to the topic of nutritional approaches to Parkinson's disease. Dr. Zwickey, thank you so much for being with us today.

Dr. HZ Thank you for having me.

Dr. LS Your expertise in neuroimmunology and nutrition make you I'd say, uniquely qualified to understand neuroinflammatory and neurodegenerative conditions. Is there a reason that you were drawn to focus on Parkinson's disease in particular?

Dr. HZ It's actually an interesting story. My focus had been nutrition and immunology, and I was contacted by a person with Parkinson's who had used nutrition to impact his disease course, and he wanted to know the why. Why was becoming vegan slowing down his disease progression? And so, he happened to have a foundation, and he was willing to fund the first bit of research that allowed me to dive into the role that nutrition played in Parkinson's disease.

Dr. LS Wow, that's a great story. So tell us about some of the fundamental nutritional approaches that clinicians can recommend to their patients with Parkinson's disease, to address neuroinflammation and neuroprotection.

Dr. HZ Certainly, and what I would say is that a lot of the nutrition research is emerging. We have new research coming out all the time. When I started in this field about 10 years ago, there was very little data around nutrition for Parkinson's, but now there's even review articles starting to appear. So as with any nutritional intervention, there are both things that need to be increased in people with Parkinson's, and things that need to decrease in people with Parkinson's, and they fall in some broad categories.

So let's talk about the ones that have the most evidence to begin with. Probably the first evidence came in around uric acid, and uric acid is an endogenous antioxidant, and there are certain foods that we eat that either increase production of uric acid, or decrease production of uric acid. As it turns out, uric acid is highly protective for Parkinson's. So people want to avoid foods that break down uric acid. Now, if you think about uric acid, probably the first thing you think about is gout, and you think about, well, you take cherries for gout, it breaks down uric acid, and that's exactly true. And so, you would avoid cherries for Parkinson's. Dairy breaks down uric acid, so avoiding dairy is critical in Parkinson's. And then there are some other fruits that people eat less of that tend to break down uric acid, things like pineapple and kiwi, but we worry most about the dairy.

And dairy is probably the second major area that has been focused upon for Parkinson's. Not only does dairy break down uric acid, dairy is also pesticide rich, and one of the things that's been shown in people with Parkinson's, is that pesticides are particularly problematic. Initially, we thought that pesticides were either causing neuro damage or being unable to be cleared, and so perhaps causing mitochondrial damage. Now there's evidence emerging that pesticides are actually killing off species of microbiota in the gut, and that that may be contributing to the role that dairy plays in Parkinson's, and that leads us to this question of whether or not people with Parkinson's should be eating primarily organic foods, foods that don't have pesticides and aren't going to have an effect on the gut microbiota.

Other food groups that we know play a role in Parkinson's are phenolic compounds, caffeine. So coffee and tea are beneficial for Parkinson's. In fact, the epidemiological data on green tea is some of the best out there. It shows that green tea can ward off Parkinson's for up to seven years. That's amazing. So increasing green tea consumption and yes, the caffeine makes a difference, as does the EGCG, so we're talking about caffeinated green tea here, but increasing green tea consumption is considered a positive thing. If somebody already has Parkinson's, there's less data. The data is better for the prevention of Parkinson's.

Then we've got things like micronutrients, and fats, and some of those areas, so let's address fats first. I think at this point, we're all aware that there are some good fats and there are some bad fats, and as you might imagine, the good fats, the omega-3s are protective in people with Parkinson's. In fact, there are studies now looking specifically at increasing omega-3s in Parkinson's, and as much as eight grams per day is needed in order to have an effect on disease course. A lot of studies that use low doses of omega-3s don't see any effect at all. So you actually have to use high doses of omega-3 to have effects on disease course.

And of course, then you want to eliminate trans fats, and trans fats are those fats that increase the shelf life of many products, and we tend to think that they've been eliminated from our food supply, but guess what? They haven't been. They're still in several crackers and cakes that you find on the shelves, and they're in things like hot cocoa. So you have to pay attention to where the trans fats are hiding out.

The other thing is the micronutrients, and from a micronutrient perspective, we're finding that people with Parkinson's tend to have low considerations of B vitamins, and remember that vitamin B6 is involved in the synthesis of dopamine. So we have to make sure that the dopamine that can be produced, is being produced, so making sure that B6 is there, and B9 and B12 have also been shown to be important in Parkinson's. We know that vitamin D is important in Parkinson's. However, I would say that the vitamin D data is interesting because we show that people with Parkinson's tend to have low vitamin D levels, but honestly, everybody has low vitamin D levels, so we have to take some of these correlations with a grain of salt. Is the low vitamin D causing the Parkinson's, or is it associated simply because everybody has low vitamin D?

Vitamin C has shown beneficial effects, specifically on differentiation of brain cells and synthesis of dopamine, and vitamin A is also important in the dopaminergic system, so all of the micronutrients really are important when it comes to Parkinson's. And when we look at the fact that again, Americans are low in their micronutrients, then doing some simple things like multivitamins, or increasing vitamin intake is important.

There's a couple more things. One is sugar, and I want to bring up sugar specifically because there are camps of researchers of Parkinson's that believe that both Parkinson's and Alzheimer's disease are a Type 3 diabetes, and this is when glucose, misregulation happens in the brain. And we see that when people, both with Alzheimer's and with Parkinson's, have spikes in their blood sugar, you see fast progression of neurodegeneration, and it makes sense, right? We know that glucose is responsible for increasing reactive oxygen species and increasing inflammation, so when you have those spikes happening in a neuroinflammatory process, you're going to increase neuroinflammation.

The other topic I was just going to bring up was alcohol, because there's been some research now into alcohol, in people with Parkinson's, and the data is mixed. In general, liquor is not so good for people with Parkinson's. Again, is it because of that sugar spike that we tend to get with liquor? However, when you get into things like red wine, where there are phenolic compounds, red wine in moderation has actually been shown to be good for people with Parkinson's, as has beer, but no hard alcohol and no white wine. So, it starts to get very nuanced as we get into diet, and all we've talked about so far are individual ingredients of a diet, not entire dietary patterns, mostly because most of the studies have not been done with dietary patterns, with looking at a Mediterranean diet versus a ketogenic diet, versus a vegetarian diet. Most of the studies at this point have focused on different elements of the diet.

Dr. LS Thank you for that highly comprehensive answer. I'm wondering when you have talked about how some nutrients can affect disease course, for example, the omega-3 fatty acids, what would a clinician expect to see in their patients? Would there be an improvement in motor symptoms? Would there be an improvement in dementia, or decreased likelihood of progression to dementia, for example?

Dr. HZ All of the above. We see that when people change their diet, now changing entire diet, as opposed to changing one ingredient of their diet, we see that A, their motor symptoms improve, and we've done a study of ketogenic diet for Parkinson's where we specifically added omega-3s, but we also stabilized blood glucose, and cut out alcohol and dairy products. But we saw that the gait, meaning G-A-I-T, the gait of people with Parkinson's, immediately improved within four weeks.

Dr. LS Wow.

Dr. HZ And people felt less brain fog, right? So the effect of nutrition is the whole system. The entire body responds, not just the brain, and why is that? Is it that nutrition is specifically having an effect on the substantia nigra in Parkinson's? To some degree, sure, because we know that some of the dopamine in the body is made in the substantia nigra, but you've got to remember that the microbiota is intimately involved in the production of dopamine. In fact, we think that if the microbiota is unhappy, you're not feeding it the right fuel, then you're not getting dopamine production in the gut, and you're also not getting all of the anti-inflammatory metabolites that those microbiota produce.

So if we feed you a diet now that is anti-inflammatory, and omega-3s are one of the best anti-inflammatory foods we can feed you, you give the microbiota something to digest to turn into resolvins, to turn into anti-inflammatory metabolites, and it slows down neuroinflammation. So yes, I would say that not only will a physician notice the difference, if the physician is doing the UPDRS, which is the Unified Parkinson's Disease Rating Scale, they'll immediately see improvements in their patients, but the patients tell us that they feel the difference.

Dr. LS That is so tremendously encouraging. As you've mentioned with the gut microbiome, it sounds like it has a kind of unique composition in people with Parkinson's. I'm not sure whether that's cause or effect in terms of the impact of pesticides. Do you have any opinion about that?

Dr. HZ It's a great question. Every time we talk about microbiota, we think about the chicken and egg question. Are we observing something that was causative, or it's the effect? My gut feeling, as it is, says that it is probably causative, however, I can't prove that. In animal models, we can show that it's causative, but in humans, we can't prove it. What I would say is that the gut data started coming out in 2015, there was a seminal paper, the author is Scheperjans, and I can't remember if it's Finland or Denmark, they showed that people with Parkinson's were missing Prevotella in their gut. It was depleted, and when Prevotella was depleted, there was an overgrowth of an enterobacteria, and this particular ratio of enterobacteria to Prevotella predicted gait difficulty. When they could reverse that ratio and bring Prevotella back, people were able to walk again. Now, I don't think at that point, any of us thought that the microbiota would be related to people's ability to walk, but it turns out that it is.

There has since been a paper that came out this last year that showed the exact opposite, specifically that Prevotella was overgrown in people with Parkinson's. Prevotella's overgrown, there were actually three species of microbes that were overgrown, not just Prevotella, and there were 10 species of microbes, specifically microbes that are responsible for producing anti-inflammatory metabolites that were undergrown. So what's going on here? Are these researchers at odds with each other?

The problem with microbiota research is that we don't even know if it's the same species of Prevotella that they were observing in Europe, that we observed in the United States in this study. We also don't know if there was a plasmid or some secondary DNA in the Prevotella in one of those studies that was actually causing the effect that we see. We don't know that the Prevotella is causative, or if it's effect, and because the microbiota work together in guilds, is it the absence of the Prevotella -- the researchers in Europe did not look at other species other than Prevotella, to see if it was actually the combination of species that was causing the gait difficulty? So there are lots of differences between the studies that suggest it's complicated, and the complications just make us need to do more research into how the microbiota is playing a role, but clearly it is playing a role.

Dr. LS Yeah. It seems like what should make news is what the microbiome is not involved with. It is so complex and far-reaching.

Dr. HZ Exactly. 

Dr. LS Have fecal microbiota transplants been shown to be helpful for people with Parkinson's, given the microbiota connection?

Dr. HZ Yes and no. Let me start with the yes. Fecal microbiota transplants, which I'll abbreviate, FMT, FMT is not an accepted treatment for Parkinson's. The people who have received fecal transplants also have C. diff. Interestingly, the people who have had C. diff and have had a fecal transplant have noticed their Parkinson's go away, 100%. It's amazing.

So a clinical trial was undertaken in Belgium in 2019, and the trial is set up where people are either given fecal matter from a healthy neurotypical donor, or they're given autologous fecal matter, their own fecal matter. And that trial is ongoing, and so we don't know the answer to that. Remember that in the age of COVID, all clinical trials have been suspended, so we're kind of in the midst of waiting for a lot of these trials to end so that we can see what the data says. But the short answer is in the case studies, it has been shown to be not only effective, it has been shown to be curative. In the clinical trial, we don't yet have a good answer.

Dr. LS Well, a lot of potential there, it sounds like. 

Dr. HZ And people with Parkinson's are so excited. 

Dr. LS Apparently, Parkinson's disease is the fastest growing neurological disorder in the world. Between 1990 and 2015, the number of people living with Parkinson's doubled to more than 6.2 million, and that number is predicted by 2040 to reach 12 million. The thing I found intriguing about this research is that even when analyses account for increasing age, which itself, as you know, is a risk factor for Parkinson's, Parkinson's still seems to be becoming more prevalent. What do you think is going on here?

Dr. HZ Yes, Parkinson's is one of the neurological diseases that is highly sensitive to environmental toxicity. We know that about 70% of Parkinson's is environmentally induced, and is that the environment killing off the microbiome? Most likely, yes, but we can't say for sure. So if we think about the toxicity of our environment and the number of things in our environment that have an impact on our microbiota, we see that diseases that are increasing, Parkinson's being one, autism being another, are the ones that have an environmental driver, not a genetic driver, and for certain, the epidemiological data points to pesticides as one of the major drivers of Parkinson's. The data out of the California Central Valley, where pesticides are sprayed, and often people have their windows open in the summertime and the pesticide goes right into the house and it's breathed, but more importantly, it goes into the water supply, and in the water supply now you're drinking concentrated pesticides.

It's not just pesticides, though. We know that heavy metals are having an impact. So think about the lack of environmental precautions that are taken in China and produce acid rain, and then that rain drips heavy metals onto our food supply on the West Coast. That is problematic. We look at where heavy metals are mined in the United States, around the Great Lakes region, for example, and you see concentrated Parkinson's around that area in Ohio, and Pennsylvania, and Upstate New York. 

We also know that BPA, bisphenol-A is also playing a role in that when we have used plastics that have BPA in them, we see that they can directly kill neurons. In addition, they can kill species of microbiota. So there's so many environmental toxins, that we are designed to clear those toxins from our body, and what we're seeing in people with Parkinson's is that they don't clear them quickly enough, such that they accumulate, likely are accumulating in the gut because people aren't pooping fast enough and then killing off species of microbiota. And indeed, in Parkinson's, we see that constipation shows up seven to 10 years prior to disease onset. And so again, if you're constipated, all of the chemicals from the environment are hanging out in your gut longer, and we're going to see different species of microbes exposed to different chemicals than in people who don't have Parkinson's.

Dr. LS You mentioned this is the time of COVID earlier, but it almost seems like we need a new definition of pandemic also to encompass these new types of vectors: political and economic trends, ultra-processed food, environmental changes, it's really getting more dangerous to be alive, it seems! 

Dr. HZ I think that one of the things, when we start talking about environmental toxicity, one of the things that can happen is we can start to feel overwhelmed and really be terrified of our food supply, and our air, and our water, and one of the things we know from microbiota research, specifically from the American Gut Projects out of the University of California, San Diego, is that we can also improve our microbiota by increasing our vegetable consumption, and our plant consumption overall. So not just vegetables, but nuts, and spices, and whole grain, and doing that acts as prebiotic, and it doesn't matter at that point what diet you're on, you see an increase of diversity in the gut microbiota, and you see an increase in all of the health outcomes, the ways that we would measure health outcome. So a decrease in cholesterol, and a decrease in BMI, and a decrease in blood glucose, and all of those things that are biomarkers for health do better when we increase the variety of plants that we consume.

Dr. LS The power of plants should never be underestimated, indeed.

Dr. HZ Indeed.

Dr. LS Is there anything else you would like to be sure we know?

Dr. HZ Yeah. The thing that I have found most surprising in the Parkinson's field, is how thirsty the patients are for this information. When I speak about nutrition and Parkinson's, people feel empowered when they know what foods they should eat and what foods they should avoid because it’s something they can do for themselves. And yet, I often hear physicians withholding that information because they don't want to stress out their patient with a complex dietary regimen that might be difficult. The patients are up for it. They will do whatever it takes to have an effect on their health, and we just need to empower them to do that.

Dr. LS That's fantastic, and thank you so much for this comprehensive, empowering and hopeful conversation.