What Your Brain Is Missing for Better Mood and Memory, with Dr. James Greenblatt

The statin low cholesterols, we see a memory cognitive decline and depression, but it's reversed if you stop the statin. I mean, I think there's still a black box warning on statins and cognitive decline.

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Welcome to the Feel Freaking Amazing podcast. I'm Wendie Trubow. Ed Levitan is joining us today, and we are having Dr. James Greenblatt back on the show. Because he continues to research and evolve and transform people's lives. So he is a pioneer in the field of functional and integrative medicine, board-certified psychiatrist, and has treated patients since 1988. He's been an international lecturer on scientific evidence for nutritional interventions in psychiatry and mental illness, and is the author of several books, including his newest one, "Finally Hopeful," and his upcoming one, "The Lithium Revolution." So James, thank you so much for being here today. I gotta be careful because we have a good friend named James James, and I call him Jamie. So if I call you Jamie, I apologize in advance, but welcome, James.

Or Jim.

Jim. I can call him Jim. I'll, I'll put him in.

Call me Jim, please.

Yeah. So welcome.

Good to be with you. Very exciting times in the field of functional medicine.

And I'm excited just because you're a local and we've known each other for a while and see each other on the conference stage. So it's really great to have you.

Yeah. Ditto.

Thank you.

So what was the impetus for this, for your two new books? Why did you do them?

Well, I think both were driven by the fact that what we've been saying in the integrative functional world for 30, 40 years now has the scientific evidence to support almost all of it. So there's no arguing. And if I could just work backwards, I mean, the lithium revolution was just kind of an "I told you so," because our community's been talking about lithium orotate for 30 years. And a major study came out of Harvard this year describing how lithium orotate only, none other form of lithium, was able to reverse the pathology of Alzheimer's in mice models. I mean, dramatic study.

Yeah, that's the— all the patients are coming out saying, what about the lithium?

At what dosing? Like, this is such a low-hanging fruit. What's the dosing?

Well, that's the question. So first part of the study was they did look at the brain bank. I assume that it was at the McLean Brain Bank. They looked at brains of people with Alzheimer's compared to normals and looked at 50 elements, lithium, was low. It was the only element low in the brains of Alzheimer's. Then the next part of the study, they have these mice models that are genetically bred to develop the neuropathology of plaques and tangles, you know, early in their life. So with that mice model, they spent many years looking at lithium, and, and it's stunning. They were able to demonstrate that lithium prevented the plaques and tangles if they gave lithium to the mice early. And then they were able to show that it reversed— it reversed the neuropathology. And they looked at lithium carbonate and other forms of lithium, but it was only the orotate that we've been talking about for 30 years. So we don't know how to translate that into human dosages. And I have my educated guess that these were in mice models, but pretty stunning.

Okay, Jim, like hypothetically speaking, if a human wanted to be on lithium, is there a downside to it then?

Well, what I've been answering people as— it's really been one of the most helpful tools in my practice as a psychiatrist is low-dose lithium as well as low-dose prescription lithium. A lot of the research is just how much we would get in our water and food supply. Okay, so we know that if you live in an area with high lithium in the water, you have lower rates of Alzheimer's and lower mortality. So those are micrograms per liter. And then depending on your diet and where you live, you might get 1 or 2 milligrams in your food supply. So I'm recommending that 2 to 5 milligrams is simple and safe. And rarely, I mean, 1 out of 1,000, you'd see a side effect, and that might be a headache or something mild. So I'm quite comfortable recommending, based on the literature, that 1 to 5 milligrams as a preventative dose for individuals. There are people with genetically, you know, higher rates of mental illness that might benefit from higher doses.

So what about the people who have confirmed early, early cognitive changes, mild cognitive impairment that we would say, okay, you're starting to develop dementia, potentially Alzheimer's. Is there a role for, for us to start presumptively giving them lithium? And I'm assuming it's not the 5 milligrams, it's a higher dose. But is there a role for that?

Well, there's— I believe there's a role and there's research to support it. A couple of research studies, a major one out of Brazil looked at that group, mild cognitive impairment, followed them for 4 years. 2 years was double-blinded, and it was low-dose prescription lithium, 150 to 300. So we have a few studies like that. So it's pretty clear that lithium has a role here, and we just need to kind of understand the dosages. But then, and The safety profile is pretty stunning for the low dose.

So for someone with mild cognitive impairment, like we have the lithium orotate, I want to say it's 5 milligrams in our practice as a supplement. So can we safely be giving that twice a day to people with mild cognitive impairment with no— I mean, this is so much lower than even what the study did.

Yeah.

Yeah, I absolutely think it's safe. And I think for some individuals, you'll notice a difference. Particularly if you're looking at all the other factors that we know that might contribute to cognitive decline, like homocysteine and things like that. So it's not the only path, but with work like the Bredesen Protocol, it can be kind of life-altering.

Well, that's what I was going to ask, because do people actually feel Like I have, I've definitely been using lithium, definitely not as much as you have by any means, but I've used lithium and I would say it's a rare occasion that people actually feel a difference.

Are you talking about cognitive impairment or, or emotional dysfunction?

Like, I mean, I don't use it often enough that I'm, I feel comfortable saying that. So it, it's one of those ones that I have in the back pocket, but I don't use it that often. But coming from somebody with a lot of clinical experience with it, do you actually see a difference, uh, in either mild cognitive impairment or with kids, um, at the lower doses?

Yeah, I mean, I think the symptoms to think about where I see a pretty dramatic difference is think of the concept of irritability. Think of road rage. Think of addiction. So the words irritability and impulsivity, when that's part of the equation, I'm pretty confident I can adjust a dose of lithium to see improvement. But you're right, for cognitive decline or memory, I mean, I don't see a difference. You know, I've been teaching this and I've doctors who've used it for whether it's people in the nursing home, And what they see is a calmness and decreased irritability. The preventative model for cognitive decline in the medication studies, you had to be on lithium for over a year before there was a difference. So we're talking about— and we know Alzheimer's is a progressive 20, 30-year course. But I think lithium fits in there as that kind of— one of these modifiable risk factors.

Does it confer any protection to, like, neuroprotective ability to lithium?

Once you get the book Lithium Revolution, once you Google it or get into this, it becomes this almost too good to be true micronutrient. I mean, it's pretty amazing. It increases BDNF. It helps dendrites grow. If you mix it in a test tube, it prevents the damage of neurons. It's just so critical for neuroproliferation and kind of these neurogenerative properties. It is truly just incredible.

Jim, I know you're behind the times now. Nobody uses Google anymore. It's all ChatGPT and AI.

I still use Google, thank you very much. I'm with you, Jim. Does lithium have any role in terms of, obviously for mood dysfunction, but what about when, you know, a lot of people come to our practice and they want to get off their antidepressants. Is there any role for lithium around helping them transition off antidepressants?

I think a minor role depending on the individual. I mean, I think the, The bigger step, we do a lot of work helping people taper off. Just a good functional medicine workup. You're going to find lots of deficiencies, mostly on the path of making serotonin. And it's just striking. As soon as you just replete the vitamin D and the B12 and the folate and the magnesium, all of a sudden, tapering becomes easier. And then lithium we use kind of to support coming off the medications, but by itself it would not be enough.

And then when you're using it to support coming off medications, what does that look like on the ground?

Well, I mean, the punchline is one of the things lithium does, it supports serotonin synthesis. So it supports GABA and serotonin, so it's calming. and it actually inhibits our excitatory neurotransmitters, glutamate and dopamine. So it's got this incredible balancing, but then the dose could be anywhere from 5 to 20 milligrams. But that's usually as they're closer to being off the SSRI.

What?

We got more listening questions because I want to find out what Finally Hoping is about.

You can change subjects.

We're good.

What's Finally Hopeful about?

Well, I mean, there's Finally Hopeful is the book. Sorry to get carried away on lithium. It does happen.

No, lithium is— we attach and then we go and then we come back and we play around.

Finally Hopeful, the best part I think is the title, is that it's just a path for patients and doctors to understand a functional medicine for psychiatry. So many of it is just stuff that we've talked about for years, but kind of relating it, as I said, with the lithium to research that has been published in the last few years. So it's hard for colleagues to argue with vitamin D and B12 and folate and amino acids all affecting depression. So it's a summary of kind of a functional medicine approach.

Colleagues argue all the time.

Well, they, they do. They do. It's easier when we can say things like, have you looked at the double-blind placebo-controlled trial?

Yes. Yes. But most, I mean, even, even talking to colleagues about getting red blood cell magnesium versus regular magnesium is a challenge. And we know that magnesium's an intracellular mineral then really should be checked in the red blood cell level versus the plasma level.

Right.

So it's a, it's a challenge to get people to look at what we feel is basics.

I'd like to go bigger picture, Jim. You're, I mean, it feels as though your life's work is about transforming people's experience of their mental health from one of suffering to one of ease and, and grace. Is that, first off, is that accurate?

Absolutely. I've been in the traditional, conventional inpatient psychiatry world seeing those with the most serious mental illness struggling, and then in the functional world. And I think my goal is to bridge those gaps so people can get some relief. Yes.

So what's the biggest difference that you see between what I would call the traditional model of approaching all type of psychiatric dysfunction or breakdown versus integrative and functional medicine? What would you say is the prime, prime distinctions?

Well, I think we can get it down to one word. I mean, symptomatic-based— well, that's a few words— symptomatic-based treatment. I mean, our traditional conventional model, if you have a symptom, let's say you're sad, someone calls you depressed. The mental health community, the prescribers have no thinking other than which medication. So they're just using medicines based on the symptom. And you and I and our mothers and grandmothers and everybody else on the planet knows there are probably 50 things that could contribute to your depression. But when we— it's funny, when we were in medical school, if there was a question on depression, we'd probably have to check the box like hypothyroid, B12. I remember even pancreatic cancer, whatever. There was all these things that we learned that we would look at for depression. And now when you get out, there's nothing that causes depression. It's just a deficiency of the medication. So anyways, long-winded, symptomatic-based is our current model, and that only breeds polypharmacy. One med doesn't work enough, you add the second or the third. And versus our functional world— functional psychiatry is now a word I feel good about using— is just looking deeper at root cause. It might not be the root cause of the illness because so much of this is genetically driven, but it could be the root cause of why treatments aren't effective.

Can you talk about the— you just made the statement that so much of this is genetically driven. What are you referring to when you say that?

Well, there are kind of two, two levels. You know, there's one, just one of the most important parts of my evaluation is three-generation family history and of psychiatric illness. And it might not be someone who was diagnosed and treated, but if Aunt Susie, you know, never got out of the house or was a hoarder, you know, that tells me something. Or Uncle Charlie was in prison. So I want to know that 3 generations of mood disorders, aggression, anxiety, addiction— addiction is probably the most commonly missed. And that we know tends to run in families. Most of our major illnesses are 40% to 60% genetically driven. So that's one level, to have family history of depression. And the second, more interesting— not more interesting, but something I've been more involved in the last few years is looking at kind of this world of genetics, nutrigenomics. So we can understand how you utilize vitamin D or B12 or folate, and you might need higher doses to maintain a level, or you might have pathways that you don't absorb certain micronutrients. So between the genetics of the micronutrients and the family history of psychiatric illness are kind of that genetic vulnerability.

Do you have a favorite test that you use to look at what are people's genetics likely putting them— well, I guess this kind of comes back to polypharmacy because right now we have a lot of patients requesting testing to understand what are they going to respond well to versus what are they not going to respond well to. Is that something you're using in your practice?

Yeah, for years I was fortunate to be around when these companies started, and for a couple of years before they were selling them, I was able to use them in my practice. So those are helpful tools. But the last couple of years I've been using the Intellect DNA platform. You're familiar with that one? It's very comprehensive and it's just well-referenced. It takes a lot of time and energy, but we look at thousands of genes to better understand what's going on. So that's been the platform I've used the last couple of years.

Is that just for psychiatric or is that also for functional medicine to look at? Are you a good methylator? Are you not a good— just basic genetics?

Yeah, they have many panels, medical, mental wellness, so many panels. They've been around for a while, but they're now beginning to get some traction in the mental health space. But it's mostly medical.

And where do amino acids play? What role do they play in depression and things like that?

Well, I think a very important role. Everyone's obsessed with getting protein right now. Starbucks puts a scoop in. And everyone in the gym. And I actually found by accident— I remember exactly where I was in the '90s. I ordered an amino acid test by accident. I never really heard of it. And all the amino acids were very low in someone that was eating steak and protein all day long. So I've just— in my assessment of depression, particularly in adults, looking at levels of amino acids, because those are the precursors of the brain neurotransmitters, are one of the essential tests that I think should be done on everyone. Never thought about that.

Okay. Talk to me about— this is on a different subject than amino acids. Everyone and their cousin is on a statin, which brings cholesterol down to minuscule levels, does that have any impact on people's experience of depression because they don't have the substrate to make what they need?

You're hitting on my favorite topics and we didn't even rehearse. So yeah, low cholesterol is, you know, I think one of the most misunderstood macronutrients out there. Um, it's a precursor to every steroid hormone, right? And vitamin D. So we need cholesterol. There's a subgroup of patients that we see in the psychiatric community that have genetically driven what I call very low cholesterol. These are total cholesterols. I've seen 60, 70, 120. And they're eating, you know, junk food. So it's not dietary. These individuals— and we have 30 years of research— high risk of aggressive violent behavior and suicide. Okay, those are very, very low cholesterol. The statin low cholesterols, we see a memory cognitive decline and depression, but it's reversed if you stop the statin. Right. I mean, I think there's still a black box warning on statins and cognitive decline. But talking about colleagues, Ed, you know, I have cardiologists where, like, I was seeing the kid with ADHD. The father was depressed and memory and cholesterol of, you know, 148. And the cardiologist, you know, wouldn't stop it or budge. But when the guy stops the statin, his mood gets better. So there's a pretty clear association between low cholesterol and cognitive health.

So how do you balance that? Because cardiovascular disease— so if you don't commit suicide, cardiovascular disease is one of the top reasons that will kill you, right? So how do you balance the— And I'm not asking to challenge, I'm really curious, like, how do we balance the cardiologist's desire to lower the cholesterol and the risk of— well, I know, I know, risk of, of heart attack or stroke with the mood. Yeah, I mean, and I have a couple patients who have had heart attacks and their cardiologist is pushing for their total cholesterol to be under 100.

And I'm like, I am just Under 100.

Under 100.

Well, yeah, go ahead, Ed.

No, I was gonna say, I mean, the right now there's even in functional medicine, there's a big trend to push cholesterol down. The thing that just like depression we were talking about, not all depression is the same, not all cholesterol is the same. So You've got to look at your— if they're putting plaque down, things like that, to really stratify. Is there an increase in heart disease? Because that's all we care about, right?

Yeah. I mean, you know, when patient— you know, the hardest part of patients put in the middle between, you know, two doctors. And I just— a couple docs with this very, very low cholesterol, you know, I've just sent them the articles. Most cardiologists don't care. I didn't realize they were actually trying to get it under 100. And my question has always been, you know, how low do they need to go to get the effects that they need? And I just don't know in terms of the cardiovascular literature.

Yeah, part of it, I'm definitely not up on the latest and greatest, but as far as I know, they don't actually care as much anymore about the numbers. They care that like how, how high do they put up the torvastatin? Is it 640 or 80? And they don't care as much about the number. They care just that it's at certain levels. So even though it's what I just, I found out a couple of years ago, which I didn't realize is 95% of any statin is benefit is in the first, like, 5, 10 milligrams, and everything else is just pushing the tiny bit of benefit. So it's very interesting. Anyways, I'm on tannin. What else should we know? What else should we ask?

Pivoting.

You know, I think the most important part of this book is, is, you know, everyone is different. I mean, I guess that's the core message in all of functional medicine. And certainly for depression. So just because your neighbor benefited from taking a vitamin or a supplement doesn't mean your depression will respond to that. So it's a path to help people see their differences and work with their doctors to get testing. Some of it is simple and inexpensive and covered by insurance. And so I think that's the biggest message that I trying to convey out there that everybody's different and we need to look objectively what that difference is.

So what would you say if, if somebody didn't have access to a functional medicine doctor, what would be the top 5 to 10 labs that you would recommend for somebody that doesn't feel great?

If, if we're talking about depression, let's go back to what we learned in medicals. Come in would be the vitamin D, significant implications for mental health. So vitamin D, B12, thyroid, iron, zinc, magnesium, and an MTHFR genetic test. I mean, I personally think— I think I got 6 there, but that could literally change the face of mental health treatment, particularly for those individuals in low socioeconomic groups who are maybe seeing a psychiatrist once a year for medication refill. I have docs that I've worked with in community mental health clinics where they're not allowed— psychiatrists and nurse practitioners— to do any testing.

Oh, that's possible.

They're told, you don't do testing. Your job is to prescribe. The PCPs can do any testing. Wow.

That's just amazing.

I'm going to keep my mouth shut.

I wonder where that came from. Anyways, big, big pharma that wants people to prescribe.

So that's a pretty short list, Jim. Like, honestly, that's not a— that's not a—

I asked for a short list.

Yeah, that's not a ridiculous amount of things. What about the role— I mean, so, you know, we live in the Northeast, and, and I was just thinking today, normally every Tuesday morning I go to my favorite park and I do a loop, and it's a 2.5-mile loop, and I love it. And I go once a week just because that's what works. But in the winter, like, you know, right now we have about 3 feet of snow on the ground and I am not going. So I'm not getting outside. I'm not moving the way I normally move. I'm at the gym and it's not as interesting, so I don't go as often. So how— what role does exercise and getting outside and sleep— is there some way to quantify like, okay, we can improve your depression by X percent if you do these things? And then you're left with some percent that you might need medication for.

Yeah, I mean, I think in kind of our lifestyle medicine hat, if we think of diet, sleep, and exercise, I mean, there's not better antidepressants out there. I mean, if you put optimizing sleep against an antidepressant, exercise has been shown to be as good as any medication. And certainly we know now we can say the research confirms ultra-processed foods affect depression. So absolutely, those lifestyle changes would be immense and support recovery. But for many people who are struggling with depression, I mean, the thought of exercising, the thought of eating healthy is challenging. But absolutely, those three Lifestyle factors are huge. And, you know, in the world as a psychiatrist, usually those would be second, um, to optimize the nutritional deficiencies first and then work on that. But for people in the community, people seeing their PCPs, that often should be the first step to make changes in someone who's struggling with, um, mood changes.

Thinking about that, like, how can we, how can we find people before they're in the place where they're too depressed to cook for themselves? You know, like how to intervene before they get that bad. Because sometimes, sometimes we don't see people for months and then they show up and they're that bad. And I was like, I wish you had come in a few months ago. I could have intervened earlier. So are there signs that people can point to to go, okay, I need to go in and see my provider? What are the things that people should be on the look for?

Well, I think going back to the family history, even though Patient A is no evidence of depression when you're seeing them, say they're 30-year-old, that family history would just kind of put a little star and would want to routinely look at some of these kind of risk factors. And again, some of the blood tests like B12, homocysteine is one of the most significant predictors of depression down the road. So if there's that family history, it might be, you know, just like we're going to monitor our lipid panel once a year or whatever you guys do as PCPs. As a psychiatrist, if there are risk factors, I'd want a yearly checkup of these known risks for depression.

What's your goal for the homocysteine level? Or where's the homocysteine level at which you start to be worried about risks for depression?

Well, I start thinking about it over 10. But I don't really— the patients we're seeing are 15, 20, 42s. Stuff like that. That's where we see significant deficiencies in the B vitamins associated with depression and dementia. And again, we've had that research for 25 years that elevated homocysteine is not only, I guess, predictive of heart disease, but predictive of depression and dementia. But there's no model of prevention in psychiatry.

Is there anything that we should ask you that we haven't asked you? Like, this has been very wide-ranging. Is there, is there anything that you're, that you wanna make sure that we tell the listeners or that we tell people?

Yeah.

Or where, where they can find you too, if they have more questions.

Sure. You know, my website, jamesgreenblattmd.com, has kind of my book and we're setting up courses for consumers around these topics so people can get more information. And, um, so that would be the easiest place to find me.

Amazing. Thank you. This has been, this has been amazing. It's always great to catch up and get the latest.

So yeah, nice talking to you. Keep up the good work, and there's a lot to do.

Yes. So for the listeners, thanks for listening. And for Dr. Greenblatt, Jim, thanks for being here. This was really cool.

Take care.

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