This episode of the podcast features Dr. Dan Stickler, Neurohacker Collective’s medical director. He is the cofounder of the Apeiron Center for Human Potential and the Apeiron Academy. Disheartened by our current “sick care” approach to health, Dr. Stickler created Human Potential Medicine- an integrated, biospherical systems-approach that combines the scientific grounding and expertise of modern medicine with leading-edge genetic/epigenetic science and neuro-psychophysiological modalities to expand human capacity. He discusses the foundations of cognitive chemistry and the nutrients the brain needs for optimal performance.

Show Notes

0:00 Intro
1:39 Foundations of cognitive chemistry - what nutrients the brain needs
4:45 Micronutrient deficiency
8:03 Brain nutrients: Amino Acids
9:24 The role of amino acids in neurochemistry
12:00 The role of micronutrients
13:36 Mineral-depleted soil impacts micronutrient profiles in organic farming
18:02 The relevance of nitric oxide
20:23 Key things people can do to get foundational amino acids
22:33 Proteins to avoid
24:33 Amino acid testing
25:27 Sufficiency on a vegetarian diet
27:39 Essential amino acids
28:46 Plant sources of complete proteins
30:20 Evaluating supplements based on goal of optimal health, not ‘natural vs synthetic’
32:33 Synthetic chemicals with meaningful health benefits
39:44 How to do science comprehensively well
41:22 From science to sensemaking
43:30 The limitations of pharmaceutical drug development through clinical trials
46:52 Cognitive chemistry foundations: fats
48:15 Role of cholesterol
53:06 Trans fats and oxidized fats
57:07 Oxidized cholesterol
1:00:52 Good dietary sources of omega-3s
1:05:30 omega-3s from consuming animal products
1:09:03 Chronic disease and inflammation
1:10:11 Wild caught and grass fed vs commercially raised animals
1:11:34 Sources for evaluating omega-3, omega-6, and fatty acids
1:16:16 Micronutrients
1:17:55 Magnesium
1:18:46 Copper and selenium
1:23:33 Iron
1:31:06 Micronutrient product lines
1:35:38 Choline
1:38:25 Lecithin

Connect with Dr. Dan Stickler:

• The Ironman Executive podcast
• @IronmanExecutiv
• Apeiron Center
• Apeiron Center for Human Potential - facebook
• linkedin

Links from the Episode:

• Empty Harvest - Bernard Jensen
• Vegan Bodybuilding & FItness
• Mark’s Daily Apple
• Robb Wolf
• Bariani Olive Oil
• 6 Tips to Buying Better Olive Oil
• Adulterated or Fake Olive Oil
• Is it safe to cook with olive oil?
• Is it a Good Idea to Cook with Olive Oil?
• Nutritionfacts.org
• Head Strong - Dave Asprey
• Know Your Fats! - Mary Enig
• The Zone Diet - Barry Sears
• Walsh Research Institute
• Metagenics
• Thorne Research
• XYMOGEN
• Gaia Herbs

Transcript

Daniel S: Okay, welcome to the Neurohacker Collective podcast. My name is Daniel Schmachtenberger. I work here in research and development. We are delighted to have Dr. Daniel Stickler with us today who has joined the team not that long ago as our new medical director. He is also the medical director of Apeiron Academy and Apeiron Health Centers. Dan has a really fascinating background in medicine starting out as a surgeon, getting into bariatric surgery and then getting into lifestyle from there and getting into all things, health, wellness, anti-aging medicine, cenegenics, hormone optimization and then deeply into genomics.

Applied genomics and epigenomics has a great platform for training practitioners and how to do genetic assessment and nutrigenomic work and like that. He happens to be one of the few medical doctors in the United States that has done a really deep dive into nootropics and cognitive chemistry and in the integrative psychiatry but on the performance optimization rather than on the disease management side of psychological and cognitive wellbeing. He created a great course in nootropics, which is how we connected.

Dan, it is a delight to have you here today.

Dan Stickler: It's great to be here.

Daniel S: What we're doing is this particular podcast will be the first part of a three-part series on cognitive chemistry. For those who are listening who are interested, there's a lot of things for cognitive enhancement that are outside of chemistry. We can do EEG neurofeedback which then could talk about. We have many people who will talk about. We can do meditation stuff. We'll have a whole series on sleep. There's a lot of things that are relevant to the cognitive space but we really want to dive in on understanding all the foundations of cognitive chemistry. We're into this three-part series together with Dr. Stickler.

The first one that we'll do today is on the foundations of cognitive chemistry which is what nutrients the brain needs to do all the things that it does well and how to make sure we're getting those and what kinds of toxins, pathogens, issues can affect cognition and how to avoid those and like that. The second part that we will be doing soon will be on nootropics and smart drugs and specific cognitive enhancement supplemental chemistry. Then the third one will be on more advanced topics that people usually do in relationship to a medical practitioner so specifics to how you can do cognitive chemistry more dialed into you based on genomics and based on assessing hormones, assessing neurotransmitters, those kinds of topics. This should be a really fun three-part series. We dive in today with foundations because we really want people to do the more advanced work and supplemental work on a healthy strong foundation. This is our goal for the day.

Dan, if we take the model of the Chinese medicine model, we look at excess and deficiency. We can have issues from deficiency. What are the nutrients that we need to get enough of for the brain and nervous system and associated physiology to work well where if we have any kind of deficiency, then we can problems. Then what are the things we can have access of either excess of a nutrient that we need like sugar or copper or whatever or toxins that we really shouldn't be in the body and all toxins that aren't being excreted well, pathogens which were a living subset of toxins.

I think if we look at the model of what are the toxicities we want to avoid and decrease, what are deficiencies that we want to increase and then what are the regulatory issues whether we're talking about from a genetic or sleep or mindset or et cetera, like regulatory dynamics. I think maybe that will be a good model for us to explore. Does that sound good?

Dan Stickler: Yeah. That's like a textbook you're talking about there.

Daniel S: All right, we won't get all of it for sure.

Dan Stickler: Yeah. That would be several hours of conversation to address the deep dive into those. I think keeping it to the more common areas that most people are familiar with probably will be the best way to go with that.

Daniel S: Let's start with deficiency nutrients. Just to clarify, when we're talking about deficiency, we're talking not clinical deficiency meaning someone has low enough levels of vitamin D, they have Ricketts or if they have low enough levels of vitamin C, they have Scurvy. Between optimum levels and a full on disease state is a pretty big room for suboptimal and so we want to talk about what are optimal ranges for various nutrients that are needed for not just health in general but specifically cognitive and psychologic health. If people are new coming to this, what are the foundations of nutrition that are relevant for brain health and chemistry?

Dan Stickler: Well, I think it would be best to start off by clarifying deficiencies and excesses. Some of the nutrients have a very narrow spectrum of deficiency and excess that they're very narrowly focused into a range of optimal. Bruce Ames did a really good job of talking about micronutrients and his triage theory of them. I think it applies well from what I've seen in clinical practice where the body has two different mechanisms at work. You have the everyday function, the survival function where it's using certain nutrients and they're allocated to the everyday survival. Then in the background of that, we also have long-term survival and long-term aspects of DNA repair and monitoring and things like that.

When we get deficient, we may not have overt signs of deficiency because it's being triaged so they're taking the limited amount of nutrient that we have, the body does this and allocates it to the things that we need for our daily survival. We may not be aware of this ongoing deficiency if some micronutrient or a macronutrient even that could be impairing long-term survival benefits. Looking at it from a symptomatology standpoint, it's vague when we go with symptoms. What we want to look at is, what are the items that are really significant that we need to get in every day to maintain not only that daily aspect but also that long-term survival piece.

Daniel S: Yup. Long-term survival and optimization obviously go together. Because if we have enough calcium in the blood for all the critical calcium ion channel stuff that has to happen daily but we're moving slowly into osteopenia where some of the reserves are decreasing. We're also moving into suboptimal function even though we're still asymptomatic.

Dan Stickler: Yeah. We have systems in place. The body is capable of making many things but we also have essential nutrients and then we have what we call conditionally essential nutrients which are nutrients that the body can make but under stressors or increased demand, the body can't keep up with these so we need to get those into our diet in some way.

Daniel S: Do you think amino acids are a good place to start for brand new print?

Dan Stickler: Yeah. It's a great place to start. I mean, we deal with amino acids. The body is capable of making most of the amino acids but we also have the essential amino acids which the body can't make. We're one of the few organisms on this planet that can't make all of the proteins that we need in our body. We have to have certain amino acids that are going to be able to be taken in a diet that we're not capable of making but we need to survive. Having a good balance of that intake of protein is essential. Proteins have different biologic values when it comes to the amount of essential amino acids that are present in them.

We see a lot of issues with people who have low protein intake that are vegetarian and so it's not that the vegetarian aspect is in any way negative. It's something you want to pay attention to because you will need to supplement certain things to maintain adequate nutrition especially of cognitive function in that situation.

Daniel S: For those who don't know, what is the role of amino acids in neurochemistry?

Dan Stickler: Well, the amino acids are the building blocks of all proteins and there's these proteins can take the form of receptors, they can take the form of neuromodulators. There's a building blocks of what we require in order to function in an optimal state. When we don't have that ability to build it, it's just like you're building a house and you have all of the essential pieces to build that house but the nails are missing. You can have all of the additional wood and you can have excess of bricks and everything like that but if you're missing the nails or the mortar, then you're not going to have a solid structure. Then it goes the same with neurochemistry. If you don't have all of these nutrients that are there to balance out and make everything that's needed, you're going to end up with deficiencies.

Daniel S: I think specific, simple, interesting point for people is that the brain has a lot of different signaling chemicals, peptides and endorphins and neurohormones and the neurotransmitters that many of us are used to hearing off. Dopamine and serotonin are the most commonly heard of happiness related kind of psychiatric hormones … I mean, transmitters are both made directly from key amino acids. Tryptophan converts into serotonin and then melatonin to sleep and dopamine …

Dan Stickler: Tyrosine.

Daniel S: … or tyrosine, I mean, dopamine from tyrosine [inaudible 00:11:09]. This means if someone is not either getting enough dietary amino acids. They're not getting enough protein or they're not breaking it down or absorbing or assimilating it. They literally don't have the building blocks necessary for key neurotransmitters.

Dan Stickler: Right. I mean, you've got a look at it from the total system standpoint too. Do they have the mechanisms in place to utilize these amino acids as well? You've got to not only have that precursor piece but you've got to have the steps in between to get to that final output. We've seen some issues with that with some of the tyrosine hydroxylase deficiencies where you can get adequate amino acids but you're not actually converting it into the dopamine in the end result.

Daniel S: We'll move from amino acids for a minute, what are some of the micronutrients that are necessary to convert amino acids into neurotransmitters?

Dan Stickler: I think it's important to really define the micronutrients. The micronutrients are the vitamins and minerals that are required and most of time, these are required as co-factors. They're required in those steps that I was talking about of going from the tyrosine to the dopamine. What are you going to need in there? What pieces might be deficient that could impair that? B6 is a common micronutrient. It's a common deficiency that we see. It can be a rate-limiting step in the creation of neurotransmitters in the brain when we have deficiencies. Vitamin D also another one, B12 another one, magnesium, copper, zinc, these are all micronutrients that are fairly common as far as deficiencies are concerned.

In the American diet, we talk about how balanced our diets are and everything but are food chain has become very deficient in these micronutrients. A lot of people will say, "Well, I'm going to get all of my micronutrients from food." Then fortunately, when you look at the micronutrient content of the food that we're eating today relative to 50 years ago, there's significant deficiencies in those micronutrients that we had historically had plenty of.

Daniel S: Since that maybe unfamiliar for a lot of people, why is it that even if someone is eating healthy food, they're eating raw produce or cooked but fresh produce, even organic, they might have less micronutrients than specifically why is that such a big deal for minerals?

Dan Stickler: Well, for minerals, it can be pretty substantial or soils are becoming depleted and that's where most of the micronutrients of the foods that we consume are coming from and you see it. We really focus on organic foods and we're all excited about organic foods in the health components of organic foods. Much of the organic farming can result in even greater deficiencies in the micronutrient profiles of foods of the vegetables. Nathan, can't think of his last name but he's the big researcher in the nitric oxide. I had a conversation with him. We were talking about the nitric oxide content of kale and beets and things like that.

He had done a study on organic versus commercially farmed and found that there was a significant deficiency in nitrates in the kale that was organic relative to the commercially farmed because in the commercial farming, they were adding nitrates to the soil. That's what the plants we're using. We have to understand that it's not just the fact that we're eating a plant but we have to understand that the environment that the plant grows in is going to be essential in the micronutrient component that that plant contains that we essentially get.

Then we've got the aspect of glyphosate with the commercially farm stuff which is a heavy metal key lighter which means it binds up to metals which are micronutrients. The minerals, it will bind them to the point where we can absorb them so it will take out positive cat-ionic micronutrients like copper, zinc, selenium. Those kinds of things will be bound up so that we can absorb them. You've got to look at the bigger picture of everything when we're talking about getting these micronutrients from food and understand truly what you're getting and what you're not.

Daniel S: I think when I first started studying health and nutrition, the book Empty Harvest by Bernard Jensen is one of the first ones that I read where he …

Dan Stickler: Great book, yeah.

Daniel S: … went deep into the effects of modern agriculture and modern cropping and et cetera on soil health and the decrease micro biome of the soil, the decreased humic and folic acid content as well as decreased trace minerals and of course, that comes through into the plants. For those who've studied it, they know. For those who don't, traditional agriculture typically puts three primary nutrients into the soil, NPK, so the critical things, potassium, nitrogen, phosphorus that the soil absolutely has to have to grow plants. The other 72 plus trace minerals and all of the micro biome and et cetera that are necessary are not going in there. It can get very deficient in that.

You just brought up one of the very few examples that might be possible of if someone's doing organic where there are not getting nitrogen up high enough, you might actually be low in nitrate. I'd be super curious to see the sample size and where he was sampling from on organics, because obviously someone can do organic where they are not getting nitrogen or potassium or phosphorus high enough. In general, if they turning stuff back over and putting it back into the soil, the likelihood that things other than those three are much higher is going to be high.

Dan Stickler: I think he actually sampled from three different states, organic farms from three separate states, right on what the use of the farm was or anything like that.

Daniel S: With regard to organic, obviously, more nutrients from a more comprehensive set of fertilizers than three minerals is one goal but really the much bigger goal is avoiding the pesticides, herbicides, fungicide they put on. I would buy organic and supplement nitric oxide any day, wouldn't you?

Dan Stickler: Yeah. I actually take beet root crystals to boost my nitric oxide levels.

Daniel S: Since we're touching on it, in case people don't know what is the relevance of nitric oxide?

Dan Stickler: Nitric oxide is one of my favorite nutrients all together. It has three really different separate components. You have the neuronal nitric oxide which exist predominantly in the brain and you're dealing with it working as a neurotransmitter. It works as a free radical scavenger but it can also swing the other way and create these peroxynitrites if you're not balanced and keeping it in a really homeostatic state. Then we have the inducible nitric oxide which has a lot to do with the help of our immune function.

Then we have the endothelial nitric oxide which is something that really is a solid predictor of long-term cardiac risk. It has to do with our ability to … of our vessels to really be resilient when it comes to blood pressure changes and things like that, post-ischemic events, those kinds of things.

Daniel S: As far as the peripheral nerves go, one of the fun things where I think many people heard about nitric oxide first is part of its neurotransmitter role is involved in transmitting sensations of pleasure. Nitric oxide deficiency and then had only a copper may together.

Dan Stickler: Well, on top of that, people who don't respond to erectile dysfunction drugs. They are almost always deficient in nitric oxide. You boost their nitric oxide, a lot of times they don't need the erectile dysfunction drugs and those that aren't responding, you give them a boost of nitric oxide. Sure enough, they start responding to the drugs.

Daniel S: Right. We didn't bother selling it but we made a really fun cocktail of that PDE-4, PDE5 inhibitors and nitric oxide boosters and all that fun stuff.

Dan Stickler: Yeah.

Daniel S: Coming back to protein and amino acids for a minute, amino acids are the building block of protein. They are foundational for making neurotransmitters. They're also foundational for making just structure everywhere including neural tissue structure. As far as foundations go, because we can supplement and so obviously, for dopamines and catecholamines is why we have the DLPA and the N-Acetyl tyrosine and the quality of it. To just have foundational amino acids efficiency, what are some key things people can do?

Dan Stickler: Well, truly supplementation if you're not taking complete proteins in the diet and that's the key. First and foremost, take complete proteins in the diet. I mean, you're talking about proteins that are more complete would be things like a whey protein concentrate or an egg protein. You can get complete proteins with vegetable sources but they usually have to have added pieces to them. You have to have quite a variety of vegetables to get all of the essential amino acids in there because vegetables are notorious for missing certain essential pieces.

If you mix it up really well and … I mean, it really takes some good planning as a vegetarian or a vegan has to really plan well with the vegetables that they take throughout a day so that they can create that complete mix of these essential amino acids or they will be missing certain once like missing the nails for the house. I mean, you could have all these great material to build the house but without those nails, you're not going to have a solid structure. That's what happens in the body when you're missing one of those key pieces. Tyrosine is a big one. There's not really much toxicity with amino acids.

I mean, you can have … the body will tend to take the amino acids and through gluconeogenesis, it will actually create carbohydrates out of them. It will just break them down if you have an excess of the amino acids. You're not really at risk for getting excess but it's very common to get deficiencies in the amino acids. That's why supplementing with the amino acids either in a protein powder or in a supplement that's very directed at the mix that's required for the brain like qualia gives you that baseline that at least keeps you above that deficiency threshold.

Daniel S: Are there any particular proteins that you suggest people avoid or that they might want to avoid?

Dan Stickler: I don't prefer the soy proteins. I know this isn't going to gain me any favors of the vegetarian community but the soy protein, soy just contains too many things that are potentially toxic to the body. I mean, you're talking about the lectin contents. You're talking about the SERMS, the estrogen receptor modifiers. Those kinds of things which I've seen some very negative impacts from those. The argument goes both ways. You talk about red mean and you talk about the carcinogens and the toxicities that are associated with that. It's always a balancing act between these two. I fall in that mid-range where I like the eggs and seafood as my primary protein sources.

They give a pretty complete mix with those. When you're dealing with specialty diets that are not really conducive to the human physiology, they're not ideal for the human physiology. You're going to have to get some of those based nutrients from somewhere else. I have quite a few vegetarian clients. When I'm with them though, I actually set up their regimen base on what their primary food intakes are. I do end up supplementing them a little bit more with the other end of the spectrum and the paleo and Atkins style eaters. I mean, I'm dealing more with mitigating toxicities and inflammation. It's not like, okay, well there's a perfect diet that is ideal, you've got to balance that between individual preferences that people have.

Daniel S: Now, for people who are wanting to dial it in more and know if a diet they're on is really working well for them, do you do amino acid testings? Do you know if amino acids or something like that to get a sense of where people's amino acid profile is?

Dan Stickler: I used to do those. The amino acids … I mean, unless you're looking at a glaring deficiency on those tests, it's not that helpful. The meal you had the night before is really going to affect what you're seeing in the blood. It's just the test by itself looking at adequacy. It's more of just looking at the history and the current lifestyle habits. I'd rather have people document their food intake for two weeks than spend the money on amino acid test in general.

Daniel S: Regarding sufficiency with protein for different body types. There are obviously some people who went vegan, felt healthy for a while and then started feeling like they run into some challenges. Other people felt less healthy right away, other people felt healthier enduringly. There's obviously how someone does it. There's also genetics that are involved and other physiologic factors that are involved, speak to that.

Dan Stickler: The first thing I know with most people that go into vegetarian diet is that they generally thrive initially. They're all about it. A lot of it has to do with the calorie restriction. Low calorie intake is pretty common with the vegetarian diet and people feel really good on that. They also feel good because they're getting rid of some toxicities that they're going to get from the meats but vegetables have their own sets of toxins as well.

What I find is, and it goes back to that triage theory of micronutrients, is it's not a complete diet. We're omnivores by physiology and we require certain nutrients. You can do well, you can thrive for a long time on the vegetarian diet if you're monitoring those micronutrients and making sure you're supplementing the risks for deficiencies. What happens is over time and it may take 10, 12 years of being on the diet, I've seen people that went 15 years before their health really collapsed. That triage theory is that background stuff, it's really required for long-term health and optimal thriving. It's put on the back burner and just does not function well.

The overt stuff that you're going to pay attention to, you're going to feel bad and you're going to see that but you're not really paying attention to that deep stuff that is all about long-term thriving. Like I said, it's not that you shouldn't do it, it's just more of really paying attention to the fact that this is going on and making sure you're doing things to mitigate that potential outcome.

Daniel S: Just to clarify and wrap up a few things for people, essential amino acid is an amino acid we have to get from food. Other amino acids are ones that our body can create from the essential amino acids. Complete protein contains all the essential amino acids, eight of them, our body has 23 or so primary amino acids that are involved.

Some proteins like eggs have all 23 or most of them because it's everything necessary to make a little creature, right?

Dan Stickler: Right.

Daniel S: It has a particularly easy time providing all the amino acids if the body is having a hard time converting them for other deficiency reasons, which is why some people do particularly well with those like beyond complete proteins. Most plants, they all have amino acids but they don't necessarily have all eight essential amino acids, most of the time, they don't. If you get a wide variety of different legumes, beans, nuts, seeds, grains, you're going to get different amino acids profiles from each. Where people get amino acids from food, pretty wide variety is relevant.

Of the few plant sources of complete proteins, if you're not taking extracts like a brown rice protein which represents 1 or 2% of the total brown rice, the algaes are particularly unique source.

Dan Stickler: Okay.

Daniel S: I think it's worth mentioning if people do Spirulina, Chlorella blue green algae, they're just kind of micronutrient dense across so many categories detox and-

Dan Stickler: Yeah. They have much more than that even, I mean, those are awesome.

Daniel S: Yeah.

Dan Stickler: Good supplement.

Daniel S: I do know a lot of people who are doing kind of vegetarian vegan super food oriented diets, algaes, bee pollen things that are very nutrient dense, amino acids dense or something they oftentimes supplement as a food source with. If someone wants to learn more about protein and amino acids and getting enough amino acids on a plant-based diet, I'll just recommend real quick. I think there's a website called veganbodybuilding.com that has a lot of good resources and a lot of athletes have kind of really dialed that in.

If people are wanting something closer to Paleo side, what would you say as a good best resource for people?

Dan Stickler: I like Mark's Daily Apple and Robb Wolf's website. They're biased. You're going to get bias on either end of what you're doing.

Daniel S: Yeah.

Dan Stickler: There's not really a good place to go for a nice balance of saying, "This is fine but here do this."

Daniel S: Right.

Dan Stickler: We deal with like I said when we're dealing with it, we have people who are Paleo, Atkins, Ketogenic, vegan, vegetarian so we have the full spectrum of clientele. Here's the thing that people tend to be very judgmental about foods and supplements even. People will say, "I'm not going to take a synthetic medication but I'm okay taking any of these natural or herbal." I think we need to step back from that and realize that really, what's the ultimate goal? The ultimate goal is to achieve optimal health and really within an environment that's sustainable.

When I look at supplements, when I look at medications, when I look at foods, I look at it as input to the body and when you do that, you're not labeling it according to source or anything like that. You look at it as an input. Okay, is that input sustainable in the environment? Great. Does that input achieve the results that I'm looking for and does that input create any side effects that might not be desirable?

Instead of saying, is it natural? Is it synthetic? Start saying, let's look at the input and get rid of the judgment around what you're dealing with. Some people say, "I don't want anything that's like this herbal voodoo stuff," and others will say, "I don't want any of this synthetic voodoo stuff." It's not a matter of that and I respect people's opinions on that. I had a guy the other day that really said, "I respect what you're saying but if it comes down to an equal opportunity or equal outcomes or they're pretty close, I prefer to go with something more natural." I said, "Yeah. I believe that too and I definitely would do that but I'm not going to hesitate to at least suggest something that may not be natural, that may give a better benefit," and give them the pros and cons of that.

Daniel S: Give me an example of a synthetic chemical that you think has the positive way for meaningful health benefits.

Dan Stickler: Synthetic chemical?

Daniel S: Mm-hmm (affirmative).

Dan Stickler: One of the medications that we use is metformin, okay, Glucophage. It has very positive results in multiple areas. You're talking about boosting mucus production in the gut which boost the bacteroides bacteria in the gut, really shifts gut outcomes. It upregulates AMPK in the cell which is one of our major targets for health is AMPK activation. We have a synthetic drug that is about five cents a day that really will help mitigate many of the long-term negative impacts of aging.

On the flipside of that, we have berberine which creates a similar response. Berberine is derived from, I think, it's from goat rue which is a pretty simple herbal to use and it can be used with the similar outcome. It's not quite strong as the metformin but then when we look back at it, metformin was … it's an extract of the French lilac. Even though it's synthetic, it's mimicked from a natural product that was used for several hundreds of years for the treatment of diabetes to help mitigate blood sugar issues.

In that situation, if I have somebody that's in a higher risk for blood sugar issues trying to get the weight under control, working with gut health, I'm going to suggest the metformin in those situations over the berberine just because it's a stronger outcome. If they say, "I really don't want to do anything synthetic," then, I'll go with the berberine. We have plenty of really amazing synthetic chemicals that have positive outcomes in the human body.

I've had discussions with people about natural versus man-made and I said, "I really like riding in a car, I'd prefer that over a horse," but you go with the technology, you go with the things that advance. Why would you go with the car over the horse? It's going to get me there faster and it's a much more comfortable ride but it's man-made versus the natural components so why do we look at the bodies in a different way than that?

Daniel S: I'm going to double click on this one because I think it's actually fun and important topic. In an area like the transportation, even getting on a horse typically people are thinking about a saddle in a bit and things that are man-made, right? Bareback is pretty uncomfortable. Even domesticating the horse, you can say was outside of some definition of natural. Then, most people are pretty happy with a car and even an airplane. That doesn't mean that they aren't without side effects, right? If we look at the whole system here and we see side effects to the environment, roads suck, right?

Dan Stickler: Yeah.

Daniel S: In terms of roads cutting up ecosystems, in terms of local microclimate warming, in terms of the asphalt, in terms of the fossil fuels, right, like they suck. If this issue that when we optimize for one element, one metric in a complex system, it's oftentimes that the expense of a lot of other metrics we are measuring.

Dan Stickler: Yeah.

Daniel S: If we consider health measured by cholesterol and LDL then statins are definitely just good for you, if your LDL is high but they might also be neurotoxic and hepatotoxic but we're not measuring for that. I think one of the reasons that a lot of people prefer natural and I would agree with this and by natural they mean arising in the evolutionary environment, is in evolutionary environment everything was co-evolving so it was factoring all of those things, right? A lot of things have to be co-factored or would have been selected for because it was really the kind of emergent property of all those factors together. It might have been millions of metrics.

If we evolved with some plans or with some animals reading them over the course of millions of years, there's a pretty good chance that all of those things have been well-factored by the selection process itself.

Dan Stickler: Mm-hmm (affirmative).

Daniel S: We make some new shit, we test three or four metrics. It does well on those, it might suck on like a thousand other metrics and we don't know. If one of the metrics we're testing in, say, longevity like with metformin, longevity is a metric that probably relates to the whole set of other metrics, right? It's like a selection criteria.

Dan Stickler: The whole network. Yeah.

Daniel S: But might it like put off of some kind of fucked epigenome for the kids, we don't know. We haven't done that level of assessment yet, probably not. In general, when we think of natural versus synthetic we are thinking about things that went through an evolutionary comprehensive selection process. I think it's a good bias but it's just an initial rule of some bias, right?

Then, we want to go deeper and say, "There's plenty of plants that can kill us," and they're very natural, hemlock is a very natural product. Then there are, whether we're talking metformin or methylene blue or whatever, there's a bunch of synthetic things that happen to interact with our chemistry in a really kind of comprehensively positive way. Maybe not every day but most foods aren't good every day.

Yeah. We think about it quite similarly biasing towards things that have already gone through an evolutionary selection process and knowing that what it takes to really understand the effects of a thing is fairly comprehensive.

Dan Stickler: Mm-hmm (affirmative). Yeah. I mean, just like the berberine though I mean, you take the berberine and it was a fairly recent use of the berberine. You weigh that against the fact that the metformin is actually been used longer than the berberine in most cases. Then we have things like Bacopa monnieri. You talk about something that was just extraordinary, I mean, one of the oldest Ayurvedic probably one of the first herbal treatments ever documented was bacopa and they combined bacopa with Gotu kola and Cardamom and mixed it Gee and gave it to everybody for stress reduction. Why they do that? It worked. It was used for centuries and now we're just now coming around from modern life and saying, "Wow, this bacopa is pretty amazing stuff."

Yeah, from an evolutionary standpoint, that was there all along. We ignored it because it was Ayurvedic medicine. Modern medicine is just like, that's just voodoo, that's old stuff but now we're coming around and saying, "Wow, this stuff really worked."

Daniel S: I'll just share this because the audience might find it interesting. Doing science is a non-trivial process. If you want to really do good science comprehensively and most of what we think of as science is not comprehensive. We can do something like phase three FDA approval clinical trials on a statin to show that it does lower LDL. That doesn't mean that it's actually good for health, right? It means that it was good for that metric. Of course, we'll see Biaxin and Premarin and so many drugs get pulled from the market after tens of thousands of people die or that we just deal with the side effects and maybe we say the benefits are worth the side effects but we're not looking at things that could have been comprehensively much better had we gone up line.

To do science means, well, which metrics do you study? Which metrics are going to be affected? Maybe millions, right? We're only going to look at a few. Like with all of our ingredients in quality right now, Dan and I are working together on doing meta-analysis and we have some other people on the team doing meta-analysis of all the ingredients.

If we just look at all of this formal scientific literature, we might have several hundreds of studies per ingredient that look at different metrics in different kinds of audiences, what was done in sick populations or in healthy or in young or in older male or female.

Actually making sense of that is nontrivial. Then you have stuff like what Chinese medicine found to work empirically for 5,000 years but we don't have formal science on it yet but we have a huge apocryphal data or what say body builders or elite athletes or different groups kind of their self-experimentation or quantified self have found has worked. I almost think of science has two narrow way of thinking about what we need to do, or think of it as sense making.

How do we actually take all of the data, the confidence margins on the data? What part of it it looks at and put it all together and really makes sense of health and wellbeing? That's really what we, like, I'd say that's at the core of what neurohackers focused on over the next little bit is how do we scale our capacity to do sense making and wellbeing so that we really know what works, what doesn't work, what does work even mean, what work at the expense of what, what could work comprehensively better across the space of meaningful health interventions and practices.

Dan Stickler: That's one of the things that drew me to Neurohacker in the first place was I've been using a bunch of cognitive nootropic enhancement supplementation for years in my clients and we got about 50/50 mix of responses. I actually was developing my own powder for a while but I was following a lot of the same rules that all these other companies did is I would find a study that said, "Hey, this ingredient works really well for this outcome and this ingredients works really well for this outcome." Great, so I've put in 10 ingredients that work on 10 different processes but never really paid attention to the interaction of each of those with each other.

That number one impressed me with the ingredients research done on Neurohacker but more so was the fact that I was getting over 95% of my clients taking the quality that were reporting positive outcomes which prior to that, it was about 50/50 of people saying, "Hey, this stuff really worked," or "I didn't feel anything different with it." When I'm seeing this really high response rate, I mean, that's what prompts me to reach out to you guys in the first place and want to get an interview with you to talk about the product because it just blew me away with what I was hearing from subjective feedback from my clients.

Daniel S: For the people who are listening, I think that what are doing here is barely scratching at the surface of what needs to happen and what we want to do. When you think about the fact that to take a pharmaceutical drug through FDA trials is in the vicinity of a billion dollars and it's gotten down to about a half a billion dollars for some, some are still more than that but then when you factor all the ones that fail in phase one or phase two trials, it might be well over a billion dollars total cost to those that make it. It doesn't mean that they actually cure anything. They're mostly symptomatic treatment, mostly with side effects and it doesn't even mean that they're actually better than nothing at all five years down the road when we end up pulling, when some of them get pulled.

There are a few that are great. Antibiotics that had a very useful applications that's been limited, of course, they've also had huge blowback wrongly utilized. The new category of immuno-oncology is pretty awesome but almost everything in cancer therapy up until this point was pretty sub-awesome. Part of why we don't know how to deal with autoimmune disease, we don't know how to deal with neurodegenerative disease, we don't know how to deal with cancer well is if the cause isn't acute and obvious and it's more complex. It's a hard thing to figure out.

There's a whole different process medicine has to take. I won't go down this road too far because then I'll do a whole podcast on this sometime. In the same way that understanding all the complex causation feeding into a disease is there's a lot involved. To understand the effective chemistry on the body and especially mixed chemistries on the body is actually fairly involved.

There's a lot of things to study. We paid as much attention as we could to thinking through whole pathways, the entire acetylcholine regulation pathway. The whole dopamine regulation pathway and where the rate limiting factors would be. If we open that up, what are all the pathways that are known of that would be affected, what the next rate limiters would be, where might there be toxicity, how do we make sure that that doesn't happen?

Then, how to actually assess all that further, right? We're doing trials, Dan and I are working on clinical trials but clinical trials really just say, "Does this thing do something on a finite set of metrics more than the placebo does." It doesn't say what is everything happening, right? The fact that we think of clinical trials as a gold standard, so if there's a bell crib of effect, why do these people get great effects and these people got shitty effects and that was only on whatever metrics. What about the gazillion other metrics? What about the longer term metrics?

How do we create much more comprehensive methods of sense making systems as complex as human biology? This is really at the heart of our mission here.

Dan Stickler: I think we're coming up on with all the metrics we're starting to look at. We're coming up on a really exciting time in this bio information age, with the quantified self stuff and everybody wearing it and contributing their genetic data and their lab work and all of this information into the cloud, into these bio informatics systems. I think we're truly starting to, I mean, we're really just scratching the surface of what the potential is going to be. It's exciting.

Daniel S: Definitely. We might do a whole podcast on AI and bioinformatics in the future of diagnosis but coming back to cognitive chemistry foundation so protein amino acids, I think we did a good initial start on that. What about fats? Fatty acids, good fats, bad fats, necessary fats, sourcing of fats and cholesterol and their relationship to the brain.

Dan Stickler: It's hard to, again, be judgmental in fats. I'm back to the good and bad. It just drives me crazy that people call it good cholesterol and bad cholesterol. Number one, they call it cholesterol is a misnomer. I mean, LDL and HDL, they're lipoproteins. They're significantly more than just cholesterol but we've got them classified as cholesterol. The LDL though, I mean, people look at it as bad cholesterol and it's a truly wonderful cholesterol. Low density lipoproteins, LDL, they transport fats all over our body for use in really healthy functions.

There are different types of the LDL and you can classify that on a particle test which is important to do but to classify LDL as all bad cholesterol and all HDL is good is really not accurate. Again, just get rid of the judgment on that and understand what you're looking-

Daniel S: For those who don't know, like what does LDL do that's useful? You mentioned to transport fats but I don't think most people know the role that it has in, say, hormones. They are in hormone pathways or what the brain is made up of.

Dan Stickler: Yeah. Cholesterol is a core in LDL's transport cholesterol as well so they're taking cholesterol around … our brain has a ton of cholesterol in it or every cell wall in our body is made up of fats and cholesterol. This LDL is transporting this stuff around and delivering it. Our hormones. Our hormones, the core component of hormones that they're produced from is cholesterol. Vitamin D is made from cholesterol. We've got all of these really beneficial aspects of cholesterol and yet we put people on these low cholesterol diets which are basically killing them because you're limiting an essential thriving type of nutrient that shouldn't be classified that way.

There are good and bad but most of the time, the good and bad are related more so to your individual genetics and how your body responds to it. You look at the French and Mediterranean paradox and they consume significantly more fat. The Mediterraneans alone consumes 40% to 50% of their calories and fat and have the lowest heart disease rate. Why is that? One, genetics and two, they consume the majority of their cholesterol in the forms of olive oil or fats in the form of olive oil. Almost 50% of their calories, they drink almost a liter a week of olive oil in a classic Mediterranean dietary pattern.

A liter a week of olive oil, I try to get that and I think it's of highly beneficial from an epigenetic standpoint. These things impact not only the direct utilization of these fats in creation of hormones and other lipoproteins throughout the body but they also alter epigenetic expressions. They can change gene expression. omega-3s and olive oil both, mono unsaturated fats and omega-3s, they are wonderful about how they change gene expression in a very positive way in people.

omega-6s and saturated fats, they can be good for some people but they can also be significantly problematic in people. It just depends on the individual. omega-3s and mono unsaturated fats typically pretty good across the board but not the omega-6s and the saturated fats. That's why it's important to understand your body's response to those because it can have a profound difference in the body's outcome with the intake of those kind of nutrients.

Everybody groups fat into one macronutrient and we don't. It should never been classified that way. You've got to look at fats as separate macronutrients. You have saturated fat, you have Omega 9, omega-6 and omega-3s and look at them from that macronutrient standpoint rather than looking at them as fats as a general recommendation.

Daniel S: Okay. I'm going to ask you a bunch of questions in there.

Dan Stickler: Okay.

Daniel S: You mentioned a pretty high amount of olive oil intake and so I imagine that's going to be an actionable step. Some people follow up with, is all olive oil created equal?

Dan Stickler: No. I'll have to send you the link that you can put in the podcast but there's a really good evaluation of olive oils. In United States, apparently, the rule is that you can still call it extra virgin olive oil and still add certain amounts of vegetable oil to it. It also happens in a lot of the European olive oils that are shipped into the United States. You've got to get it number one from a very reputable source and you want to make sure that you're getting it in a dark bottle.

People are afraid to cook with extra virgin olive oil because of the smoke point but I've spent some time in Italy with some dieticians in Italy and looked at the studies on cooking with extra virgin olive oil and unless you're deep frying with it and using it over several days in the deep fryer, you're not going to really get the rancidity to it that can create problems with the oxidation of the olive oil or the oxidation of the fats in the olive oil. You're still pretty good to go ahead and stir fry with it. You can cook on higher heat with it without the risk of significant problems.

Daniel S: I think this is a point that maybe not everyone knows, in terms of saying bad fats, there are certain kinds of fats that I think everyone really want to avoid. Trans fat like definitely and oxidized fats.

Dan Stickler: Yup.

Daniel S: You want to describe those categories, I mean a little bit?

Dan Stickler: Yeah. I mean, the trans fats, it's a fat that the body is incapable of utilizing in any way. It's like a foreign material to the body. You want to talk about synthetic, that is truly synthetic. The body is incapable of, in any way, using it and it gets stored in the body unfortunately. It's just like any of the organotoxins that we have. We store those in the fat cells in our body but trans fats are very similar, they get stored and for years we've used Crisco which was this pure trans fat paste that we use in everything before we realized that it was really creating all the health problems that are happening.

When fats get oxidized and what happens is a double bond within the fat itself will get hit with a free radical. That free radical will add an oxygen to that double bond and that creates what we call a rancid fat or an oxidized fat. Those are ones that the body recognizes and says, "Oh, this is foreign material, this is bad, this is an invader. I've got to wall it off," and they're the ones who get put into the walls of the vessels.

Daniel S: Particularly, rancid fats are the ones that have a higher carcinogenic load?

Dan Stickler: Yes.

Daniel S: If people understand that trans-fat basically means a hydrogenated fat, some kind of unsaturated fat, they had a hydrogen added so this is your margarine Crisco vegetable shortening. When you take anything that says partially hydrogenated soy bean oil, all of that should be kind of rigorously avoided.

I don't think you can eat fast food and avoid it so that's a good point. Fat that is damaged by hydrogenation should be avoided. Oxidized, so this typically happens when you're cooking particularly sensitive fats at too high temperature. You notice there are some fats that are so sensitive like fish oil or flax oil that you're keeping in the fridge all the time because they can oxidize even at room temperature over a long enough period.

Many people like to, if they're going to have their fat in touch with the pan, right, if they're going to have it at that heat, just go straight to a healthier saturated fat like coconut oil or butter or palm oil. What are your thoughts on that?

Dan Stickler: Like I said, I found that the studies on the extra virgin olive oil does not create a significant amount of oxidation even with the high heat. I used to be the big proponent of, don't use extra virgin olive oil for high heat cooking but then when the data started coming out on and I started speaking with a lot of the Italian dieticians and we looked at the data, the research data, on what it takes to truly oxidize the extra virgin olive oil, I realized that it's not only the temperature but the time.

Daniel S: Yup.

Dan Stickler: That is something that I think a lot of people missed is that they're looking at, oh, it's the high heat. It's the high heat plus the time of exposure that high heat is important.

Daniel S: Fast stir fry is going to be different than a long simmering process?

Dan Stickler: Yes.

Daniel S: I would actually love to see that data if you can send it to me and then I'll even link it in this podcast if we can.

Dan Stickler: Perfect.

Daniel S: Because I still am of the mindset that cooks with coconut oil or a saturated fat that has a much harder time oxidizing because it's all double bonds.

Dan Stickler: Yeah.

Daniel S: I'd be interested to see them.

Dan Stickler: Yup.

Daniel S: Thank you. We mentioned that cholesterol is obviously necessary. There's also issues of oxidized cholesterol.

Dan Stickler: Yeah.

Daniel S: How does that happen?

Dan Stickler: Any fat can oxidize. It's free radicals. Anytime you have a double bond and a double bond can get oxidized by an oxygen free radical because it's circulating around looking for a place to really get a donor electron there. It's looking around for these potential sites and double bonds are the clear target. The fats, the double bonds in the fats are easy pickings for these free radicals.

Anytime something is oxidizing, I mean, it's just not a natural process anymore. Once that oxidation occurs, the body looks at it and says, "Okay, there's something wrong with this and I have to do something to react to it." Any oxidation process is going to create an inflammatory response. It's going to create some type of protective response from the body.

Daniel S: When you take particularly sensitive fats and cholesterols, right, some of the highly poly unsaturateds like that are in fish and that are in good DHA-free range eggs, do you cook them differently factoring that?

Dan Stickler: The biggest thing to consider is that how much free radical production a person typically has. This goes back to looking at the whole picture of things rather than going straight to this and saying, "Okay. This is a good or a bad thing." You look at the overall picture so why do people get a negative response from a fat that's consumed that could potentially oxidize? You could eat really healthy fats and not consume oxidized fats or trans fats. If you're generating a lot of free radicals, you're going to create your own inside your body, anyway.

What you want to do is you want to mitigate all the processes that are involved if you can. You minimize the inflammation, you minimize the free radical production as much as you can. I don't think free radical scavenging is the best way to go, in general, because the body does a pretty good job of controlling free radicals in most people and the people who would benefit most from free radical scavengers are really the couch potatoes that are just not really concerned about their health and they're not going to take supplements to begin with. The ones that are eating healthy that are generally taking supplements are the ones that typically don't need the free radical scavengers because you're not producing as many free radicals from the inflammation altogether.

Daniel S: As people are starting to understand that hormones remain from fat and cholesterol, it's a big deal, right? People's testosterone, their estrogen, their progesterone, their adrenal hormones are made from fat and cholesterol. Most of the actual tissue of their brain, right, the white matter in their brain, myelin, et cetera is fat and cholesterol based.

Dan Stickler: Mm-hmm (affirmative).

Daniel S: They start to recognize what a critical thing this is. You mentioned olive oil and particularly sources that are reputable in terms of probably being not sprayed so organic extra virgin stone pressed dark glass bottle, I don't know about you, I usually get very on this brand I think it's one of the better ones I've found-

Dan Stickler: It is. I'll send you that link so you can post it but it's one of the top rated ones.

Daniel S: Yeah. What are sources for omegas that are going to be good dietary sources for people?

Dan Stickler: One of the best sources of omega-3s, you're talking omega-3s, correct? The best sources of the omega-3s would be the fish. For the non-animal sources of omega-3s then you're going to lean more towards the algae sources which are really … we've talked about this before but something about the charge on the surface of the particle that is different with the algal source versus the animal source that gives it a better quality. I meant to look that up before we talk and I forgot to get the results on it.

The EPA and DHA are the main omega-3s that we're going to get. Vegetable sources and non-animal sources of omega-3s are almost exclusively ALA, the linoleic acids. The ALA, it requires the body to convert that ALA into EPA first. One, we have to make sure that we have the genetics to be able to do that conversion. Two, that enzyme that does the conversion competes with arachidonic acid so it's competing with some omega-6s as well. That's why that omega-6, omega-3 balance is so important because if you have way high levels of omega-6, you don't have the enzymes to really adequately convert ALA and even take EPA into DHA.

Let's clarify what EPA and DHA really are. EPA is the omega-3 that’s responsible for really the anti-inflammatory effect of omega-3s. DHA is really one of the top brain health and cardiac health forms of omega-3. The process requires the conversion of EPA into DHA. A lot of people will take high dose EPA but not be able to convert it very well because of the fact that their enzymes are occupied with so much omega-6. It's important to keep that balance. I think that's why we've always recommended that keeping the balance of omega-6 to omega-3 in the diet is four to one or less. I actually prefer to keep it as close to two to one or one to one possible in clients because it really does make a huge difference in inflammation.

Our American diet is dealing with 15 to 20 to one omega-6 to omega-3 so our ability to even create DHA from exogenous sources is almost nil when we're looking at that situation.

Daniel S: Why are we getting so much omega-6 relative to omega-3? Then, talk more about the relationship of omega-6 and omega-3 to inflammation and prostaglandins?

Dan Stickler: The main reason we get it, it's the American diet. We eat a lot of fried foods. We consume a lot of vegetable oils in just about everything that we take in. Those vegetable oils are very high in omega-6. You talk about the fat content in commercially raised meats like beef, you're going to get a high omega-6 level in that as well.

Daniel S: When you say vegetable oil, so that people understand, you don't mean olive oil here and you don't mean flax oil? You mean specifically canola oil, sunflower, safflower, corn oil-

Dan Stickler: Corn oil. The-

Daniel S: The cheap ones that are used in commercial shit.

Dan Stickler: Right.

Daniel S: Yeah, right.

Dan Stickler: There's really good charts online about the omega-6, omega-3 and mono unsaturated fat content of oils. If you do a Google search, there's plenty of them that come up to give you a good idea of what the balance between them are. Like avocado oil. Avocado oil is a pretty good oil too. It's got a lot of mono unsaturated fat as well. Go ahead.

Daniel S: You were saying that we get omega-6 from those vegetable oils too much? We also get too much of it from meat. If you talk about cattle, you can get one for one omega-3 to omega-6 in certain kinds of cattle raised in certain ways but it might be-

Dan Stickler: Right.

Daniel S: -up to 50 to one in other cattle. Can you speak to that a little bit?

Dan Stickler: It's no different than the kind of diet we eat affects our composition. You are what you eat, that's essential. The same goes with the meats that we consume. When we consume animal products, we're going to get the net result of what that animal consumed. There are certain grass fed cows tend to have a little bit higher omega-3s and mono unsaturated fats. You will get grain fed cows that will have very high omega-6 and very little omega-3s. Then you have cows raised on this special clover up in Scotland that will give you huge doses of omega-3s in the meat just because of what they're consuming.

We have to look at what we're consuming. This goes the same with fish, I mean, you at look at farm salmon versus wild caught. You're getting the same amount of omega-3s. Everybody is excited, well, it's the same omega-3 content but that ratio of their omega-3 to the omega-6 is hugely different in the two. Where you're talking about twice the amount, I mean, you go from 10% of the fat in farmed salmon is omega-3 and over 20% of the fat in wild caught salmon is omega-3. That percentage makes a big difference.

A lot of this comes down to the production of prostaglandins and prostacyclins. You can create pro inflammatory or anti-inflammatory and they're the main inflammatory … what we call cytokines in the body. They're out there attacking inflammation and they're healthy for us. They're a good thing. They're out there to respond to things that are happening in our environment and protect us from it. They have different responses to what happens when they interact.

Some of them will create great amounts of inflammation and some of them will create very, almost anti-inflammatory responses when they interact. The prostaglandins and prostacyclins that are made from omega-3s are typically anti-inflammatory whereas the ones that are made from omega-6s are pro inflammatory. The way this works is the cytokines are lipoproteins so there's a protein structure and then you attach a fatty tail to it and those fatty tails are almost like a grab bag. It's like you have this mix of omega-6 and omega-3s that you reach into the bag and you pull one out.

If you're 20 to 1 omega-6 to omega-3, you're going to pullout an omega-6 20 times for every one that you pullout of the omega-3.If you're down to a one to one, it's going to be a one to one pull, 50/50 chance of what you're going to pull from that grab bag to create that lipoprotein, that cytokine, that's going to be either pro inflammatory or anti-inflammatory.

Daniel S: That it's clear for everybody, most chronic disease involve pro inflammatory conditions so we see various kind of inflammatory chemicals, cytokines and other chemicals elevated for some period of time before the disease manifests symptomatologically. We're talking about everything from diabetes to cancer, to heart disease, to autoimmune disease, to neurodegenerative disease or mostly situations where inflammations was supposed to be acute and go away and where inflammation was chronic over a long period of time then disease states evolve.

You're saying that the omega-6 to omega-3 ratio is one of the deep things to pay attention to dietarily for overall inflammation which has been one of the major indicators for likelihood for chronic diseases most of the times.

Dan Stickler: Right. The inflammation is the key to health. It is one of the true holy grails of health is keeping the inflammation in check. It's not that all inflammation is bad but typically chronic inflammation is going to be.

Daniel S: Right. With regard to animal products, you mentioned farm versus wild caught and with regard to cows you mentioned grass fed not being as good as on the clover that's probably seasonal only in some small part of the world. Is it fair to say that if people are going to make one step, if they hadn't already made this, getting off of any kind of factory farmed animal product and making sure that they're at least getting free range organic hormone free sources is going to be a pretty huge step and then finding out specific sourcing within that will be the next step?

Dan Stickler: Yeah. We could go into an entire podcast on the commercially raised animals, about all of the negative impact that can be experience from that not only from the health of the meat but the sustainability of the whole process. The glyphosate that's in the feed that goes into these animals, I mean, we're getting implications from that as well. The grass fed more organic, I mean, definitely is going to make a difference in our health and it's going to make a difference in the health of the environment by supporting that. That whole process is a very positive win-win across the board.

Daniel S: As far as the healthy fats and health cholesterols go that are relevant to foundation of cognitive chemistry, we're talking about more omega-3s and more omega-3 relative to omega-6 so less of the omega-6 from conventional commercial animal products and vegetable oils. More omega-3 from all sources in particularly good EPA and DHA sources. This is wild caught fish and wild flax fed chicken eggs and things like that.

Dan Stickler: Yup.

Daniel S: Then olive oil well sourced, avocado, coconut, nuts, seeds anything worth saying about those?

Dan Stickler: You got to be careful with the seeds. I've seen a lot of my clients that get their omega-6 to omega-3 ratio kind of mixed up by eating too much nut and too much in the way of nuts in a specific kind. I had a woman the other day that was … she was consuming a lot of almonds and when we looked at the amount of omega-6 in her diet, 24% of her omega-6 was coming from her almonds.

Daniel S: Right.

Dan Stickler: She had about a nine to one ratio. For her, all we did was switch her to macadamia nuts. The macadamia nuts have a pretty high mono unsaturated fat content. They just replaced that omega-6 with monos. What it did is it actually reduced the omega-6 to omega-3 ratio because she took out that one factor there, the omega-6.

Daniel S: Or she could have went to walnuts to get the three up.

Dan Stickler: Exactly.

Daniel S: Yeah. Is there a good source that you recommend for people to be able to see omega-3, omega-6 content, and other fatty acid content in various foods?

Dan Stickler: I typically just do a Google search of those, nutritionfacts.org which is … they've had a lot of grief lately but it's got some good information on the … like we'll use that when we're looking at how much beta sitosterol in specific foods. They're very in depth with what I do with analyzing the foods. You can search and say, "Okay, what's that food highest in omega-6s," and it will give you the list. You can pick nuts, you can pick oils. That's a pretty decent source.

I found some errors in their work but overall, at least, it gives you a pretty good idea, it's not that far off.

Daniel S: As we're talking about fats and cholesterol, there's maybe nobody currently who has been a stronger proponent for the value of fats and cholesterol than Dave Asprey and specifically-

Dan Stickler: Absolutely.

Daniel S: -with this new book "Head Strong". Some people will do better on it than other people but I was actually really impressed reading that book with a good overview of a lot of health topics I thought that it was. I think that's another resource that if you're wanting to learn more about different kinds of fats and fats that are likely to do better for them, it's a good resource.

Dan Stickler: There's a book by [Barbara Innis 01:14:44], Innis I think. It's been years since I read it but it is the bible of fats. If you're a biohacker and you really want the details of fats, that is the true bible of fats. It is in depth dive into how fats work in the body, detailing all of the chemical processes that are involved in the body.

I ordered the book off Amazon years ago and I couldn't figure out why the book was like 200 bucks. It was a textbook, I mean, it was a textbook that was that thick and it's been one of my favorite reads of any books that I've had on the fats. She did a wonderful job-

Daniel S: What's it called?

Dan Stickler: It's called, "Know Your Fats" I think is the name of it. Let m just look it up here.

Daniel S: The guy that did all the original work on eicosanoid modulation, that was the zone diet wasn't it?

Dan Stickler: Yeah, it was it. It's "Know Your Fats" by Mary Enig, E-N-I-G. Yeah, she's just written a wonderful book. I keep going back to it frequently. It's from 2000. It's an old book but man, she knew their stuff back then even.

Daniel S: As we're still on the nutrition topic because there's a lot of little tendrils. We've talked a little bit about amino acids, we've talked a bit about fatty acids. For brain cognitive health, let's talk a little bit about micronutrients.

Dan Stickler: Okay.

Daniel S: Vitamins, minerals, phytochemicals.

Dan Stickler: Yeah. I tend to, really, I'm one of the guys that leans towards low level of supplementation for micronutrients, for the vitamins and minerals. Just because we have such a depleted diet and it's really hard to get that full mix of nutrients and a low dose of a multivitamin is generally a pretty good outcome that I've seen. I've seen people come in and we found micronutrient deficiencies clearly symptomatic on certain areas and we put them on a low-dose multivitamin. I haven't seen any toxicities with it but if a vitamin says, "Take four of these a day," I take two. Because I eat a pretty balanced diet overall, pretty nutrient rich diet I think but I still take a multivitamin just because of that triage factor that I don't want to be deficient in selenium because I'm not eating enough Brazil nuts.

Daniel S: Right.

Dan Stickler: If I were going after it, I mean, I can't tell you how many days in a year I eat Brazil nuts and still, there's not a whole lot of selenium you're going to find in other foods. We see copper deficiencies in people which are pretty common and that's critical for thyroid conversion into active forms. Zinc, a very common deficiency, magnesiums.

Daniel S: Let's take copper and zinc as a fine example. Magnesium is pretty straightforward. Deficiency is almost ubiquitous and toxicity is pretty much unheard of, right? Like, more magnesium is just a good idea.

Dan Stickler: Yup.

Daniel S: It's a pretty safe way to go. I'm a particularly big fan of topical magnesium, magnesium oil because it's rate limited GI absorption. Have you played with that?

Dan Stickler: I haven't, my wife has and she really likes it. She uses it for sleep purposes and it works really well for her.

Daniel S: Yeah. There's lots of different ways to get magnesium. The reason we use magnesium bound to [inaudible 01:18:37] magnesium 3 [inaudible 01:18:38] quality specifically because of the research of it have a unique capacity to elevate central nervous system levels. Copper and zinc are interesting example because they're both absolutely essential nutrients but they can also be problematic within fairly narrow ranges. If you haven't done testing first like they're tricky ones for me, right.

Dan Stickler: They are.

Daniel S: You want to talk about that for a minute?

Dan Stickler: Yeah. There's two that we pay most of our attention to on our clinical practice and it is copper and it is selenium. Those are two that require, I mean, they have a very narrow spectrum of optimal levels and it's very easy to over supplement. I see a lot of people going to functional medicine practitioners getting selenium supplementation and they generate toxicities that can create significant problems for them.

Copper, you get too much copper and you're getting into high blood pressure. I see women with menstrual issues when they get too much copper. You can get schizophrenia and hallucinations with copper. There's a pretty diverse spectrum of symptoms that can be indications of copper toxicity. You can also see it with deficiencies.

Daniel S: Right.

Dan Stickler: You can get psychological issues with deficiencies just as you get it on the opposite end of it, you get the psychiatric symptoms as well.

Daniel S: The work of Dr. Pfeiffer that led to Dr. Walsh's work in kind of orthomolecular psychiatry, copper and zinc were right at the heart of it, right? Kryptopyrroluria and histamine disorder and methylation disorder, that was actually some of the work that when I first came across it really got me into the space, because they had such tremendous work reversing schizophrenia and-

Dan Stickler: Right.

Daniel S: -even psychopathy, sociopathy like pretty serious things through very simple methods, right? Like chelating copper and giving zinc and people's hydroxylase balance, their dopamine to norepinephrine balance, they were just different people now they had impulse control. I find this fascinating from a jurisprudence point of view, right, because if someone is acting violently because they have damaged hardware and they don't know about it, is that a punishment or is that a … give proper medicine, right?

What could be possible for the world if we didn't have a lot of people that were in low-grade psychopathology because it seems like people in low-grade psychopathology because of stress and childhood trauma and poor programming but also because their physiology just pretty tweaked out of balance.

Dan Stickler: Yeah.

Daniel S: We're not talking fully diagnosable DSM psychopathology, we're talking subclinical generalized anxiety disorder, subclinical PTSD. When you look at the copper-zinc thing, I love to send people to functional medicine docs who've been trained in Walsh.

Dan Stickler: Yeah.

Daniel S: I've been hearing many things but to get that assessment, what do you think of that?

Dan Stickler: Yeah. I love the Walsh protocol. I think it really adds significant value. Dr. Walsh is brilliant. His whole work on methylation and the copper and the zinc aspects of health, I think he's pioneered that. He's well-known in the functional medicine community but he's not that well-known. He's not that self-promoter that's out there really building up a reputation for himself. Among the functional medicine practitioners and other ones that have gone and done his training have had really amazing outcomes with their clients.

Daniel S: I'll just let everybody here know that one of the things that we're working on, we're still early in the stages of it is being able to curate all of the functional medicine, integrated medicine doctors that are trained in kind of integrative psych work and put them all online so that people who want to go get deeper work done can actually go find docs that are well-trained and then help promote the training deeper to those networks.

It's one of the big reasons we partner with them to help us with that is beyond what we could do as a company that goes direct to consumer. How can we really help the field of integrative psychopharmacology, psychiatry be advanced so that there are good solutions available to more people.

Okay. There are a lot of supplements, multivitamins that are iron free or copper free for this reason. Menstruating women usually it's not an issue, with iron at least, but hemochromatosis is not that uncommon, would you recommend that if people haven't done any testing that they go for a multi that is iron and copper free until they find out or is this based on gender, menstruation? How do you navigate that one?

Dan Stickler: Typically, like I said, I typically tell them to go with half dose of what's recommended on those and getting a low enough level. Iron is tricky, not quite as tricky as the copper but the iron can be pretty tricky because hemochromatosis is probably the most common genetic mutation in the U.S. population as far as the white Anglo-Saxon population. It's pretty common especially in the Eastern Appalachian Region. We see a lot of it. It doesn't manifest until 40's in males, a little later in females because if they're menstruating they keep it under control. If you identify it early, you can prevent any significant organ damage and keep the treatment going.

Iron is one of those things. I see more iron deficiency than I see any risk of overload. I can tell you I have just a peeve with people who crunch ice. I know about pica with iron deficiency. I used to do gastric bypass surgery, weight loss surgery and pica was very common in people that weren't taking their multivitamins.

Pica is an iron deficiency and you have this desire to … and it works in the brain and it's this desire to eat something that crunches. One of the most common desires is to eat dirt. I had a patient in my office that said, I picked up a handful of dirt and it took everything within me to resist taking a bite of it.

I mean that iron deficiency, think about that. I mean, it plays a significant role in behavior.

Daniel S: Now pica is a term from veterinary medicine. It's animals that were fed a diet that was deficient in certain minerals started eating wood or anything they could because they're craving minerals.

Dan Stickler: Stool.

Daniel S: Right. Because in animal husbandry they had such a clear insight in what the animals were being fed and they had full control over it where we don't in human medicine and then being healthy had economic benefits, I think veterinary medicine led the way in a lot of areas of nutrition.

With regard to the eating ice thing is that well … I've heard this a million times but never looked up myself is the impulse to eat ice correlated with iron deficiency an actual well correlated thing?

Dan Stickler: I don't know what the research is on it. You read about it and you say, ice crunching is common with that, but I saw it. That was one of the questions I would ask and I did 3,000 gastric bypasses. I had a lot of patients that I was taking care of. I would ask them if they were crunching ice. That was one of the common questions I would ask at followup and I followed them up long term. Sure enough, I had plenty of them that were crunching ice and they quit taking their multivitamin or they quit taking. We actually had to put them on a separate iron supplement, most of the gastric bypass patients.

The ones who quit taking it, ice crunching was very common and as soon they get iron levels back up they stopped.

Daniel S: Iron specifically, not other minerals?

Dan Stickler: Well. I mean, we saw it associated directly with the iron supplementation not the multivitamin itself. We were doing a multivitamin and we had a separate supplementation for iron with them and when they would quit taking the iron that was where we saw it.

Daniel S: Now, many people who are listening who are not working with a functional medicine doc already or an integrative doc, when they do their iron labs, they might just be looking at iron and maybe TIBC and hemoglobin, some basic things but they're probably not looking at, say, ferritin. They might not see anemia but they might so dealing with suboptimal iron levels or utilization. Can you say …

Dan Stickler: Well, I mean, serum iron is about the most useless test you can get. I mean, it doesn't give much value to outcome. I mean, you want to get that ferritin level. You want to know total iron stores of the body and it's just a little bit more expensive.

It's funny. I laugh about the fact that we get all these tests that physicians really have no idea what they're testing in a lot of cases. You ask somebody what a TIBC is and they're like, "I'm not really sure." "What does it indicate?" "Well, I don't know."

We see it with MCV on the CBC, it's a common test everybody gets, but a lot physicians and clinicians just don't really know what it is because it hasn't been something that they focused on. For us we focus on these outcomes. One of the funniest ones is free T3 uptake or RT3 uptake. You ask physicians what it means and you get varying responses of what it's indicative of and what it's testing.

We get a lot of these tests that we really just get the test and it's usually part of a package deal so we don't pay attention to it because we're looking at this other test. We get so tunnel vision when it comes to testing that we're looking at the major things that jump out. Before you know it, you're writing WNL on every lab requisition which means within normal limits. We joked about it in functional medicine saying we never looked because you just … I've seen people that had WNL written on a lab result in significantly abnormal labs that were showing up on there.

Daniel S: Right. Okay, maybe in our third session when we get into advanced topics, we'll come back to which labs are actually worth running for cognitive chemistry and then where people can go to get those.

Micronutrients, you were saying you like multi-supplementation, low level, any particular thing, any particular product line you recommend for people or things to look at?

Dan Stickler: I don't really want to promote any particular line for sure because there's quite a few good ones. You look out there and you've got … I don't even want to name them because I'll leave somebody out there that has really good product.

Generally, just the functional medicine docs have a pretty good finger on the pulse of this. They can give you pretty good …

Daniel S: For people who don't know here. If they're buying it at [longs 01:31:06] or bonds or something, the chance that it's good is small. If they're buying one that their chiropractor carries or their doctor carries, Metagenics, Thorne, Xymogen whatever, the chances are higher that the ingredients are well-sourced.

Dan Stickler: Right.

Daniel S: Yeah.

Dan Stickler: That goes the same with supplements. I mean, you want to get a company that really is sourcing really good quality organic independently-tested product. I mean, I think that's important too is independent testing because a lot of product will come from China and it's not that the China product has anything wrong with it. I found companies would say we do in-house testing for contaminations in the product. Well, you know what, they probably aren't really doing that. I mean, some do but the ones that will get a batch of product in like one of the companies I use they actually sent it out. If I send them a request and I say, in your 5HTP what's the contamination of a peak X. Peak X is what caused the eosinophilia in tryptophan years ago.

They'll ask me the batch number and they'll send me a report from an independent lab of the batch as it came in. That is good quality and that's why I stick with that company.

Herbal companies like Gaia Herb. I mean, they're locally source. They're actually here in Asheville. I've seen their facility. It's a wonderful facility. Their standards are very high. We used them quite a bit.

Daniel S: When it comes to just broad spectrum, a lot of people might not know, but if you're going to even take a mineral like say magnesium. Magnesium can be in the form of a lot of different forms. It can be bound to a bunch of amino acids. It can be found to a bunch of vitamins and they can all have different benefits and be differentially uptaken for different systems of the body. Not only do we have 72 plus trace minerals and how many ever different vitamins within phytochemical content.

For just that baseline supplementation, what you're mentioning with the multi, I'm a pretty big fan of the complex green super food powders as a way to just make sure that people are augmenting their diet with pretty wide plant-sourced nutrient profiles. Then I'm a pretty big fan of rotating them. What are your thoughts on that?

Dan Stickler: The thing phytosterols, lotus phytosterols and for me, I don't consume a great deal of vegetables. Those green powders are great. I'll put them in my protein shakes.

You can't use them as a replacement. I mean, they say, their equivalent is like six servings a day. No, it doesn't work quite that way. At least, it gives you those phytonutrients that are essential.

Now, phytonutrients, one thing to understand about phytonutrients is phytonutrients are toxins. They're toxic to the body. Enough of a dose of them and they can kill you, but their beneficial because they're toxins. This is a hormetic effect, hormesis, where we take low-dose toxins so that it up regulates our body's detoxification system. When the detox enzymes are exposed to low levels of toxins they up regulate and that's beneficial because it keeps the body on guard and it keeps it healthy and it's like training the soldiers. It's constant training for them by getting those phytonutrients in there.

Daniel S: I think it's important to say … someone can say well, I'm getting enough toxins from being in the house with volatile organic compounds and eating glyphosate and maybe like Cheetos do that for me instead of phytochemicals. Not all things that are stressors are hermetic. Some things we have evolved mechanisms to up regulate in response to, like chemicals from plants were part of our evolutionary environment. As opposed to chemicals that we really don't even have an evolved detox mechanism for and so the body really just goes into overload trying to deal with it rather than hormetic up regulation.

Dan Stickler: Right, a huge difference in the two.

Daniel S: Any other just like baseline notes on micronutrients that people should know?

Dan Stickler: One thing we didn't go into is choline.

Daniel S: Yeah, talk about it.

Dan Stickler: Yeah. I mean, we see a lot of people that have the potential from a genetic standpoint of choline deficiencies and require choline supplementation. It's a common genetic variant. I mean I don't want to call it a mutation because it's not a mutation. It's not uncommon for people to have the inability to create enough choline on a daily basis. Supplementation is essential in these and there're various forms that you can get that are important to understand.

Daniel S: Food sources, if someone was going for it.

Dan Stickler: Well, one of the greatest is that egg yolk. Egg yolk and one of my least favorite foods is live, very good source of choline. Runny egg yolks, when you cook an egg yolk, if it's not running, you're going to get about a third of the choline from that, but the egg yolk itself in a liquid egg yolk you're going to get a pretty good dose of the choline. The rest of the stuff is pretty minor contribution of choline. The body can make choline.

When you can make it and you adequate numbers to make it, it's not a big deal. When you're very active and things like that, you're going to have to get some choline and if you don't like runny egg yolks then supplementation is your next best choice.

Daniel S: For people who don't know, why is choline relevant?

Dan Stickler: Choline is a very ubiquitous nutrient because it's involved in so many processes. Acetyl-choline, so choline combines with this acetyl co-A to form acetylcholine and it is the most ubiquitous neurotransmitter that we have. I mean it's not only responsible for neurotransmission in the brain, but also the neuromuscular junctions. It's what the nerves tell our muscles to fire. They're being told by acetylcholine. It's really an essential substance to have in our bodies at adequate levels.

Daniel S: Yeah, motor process, sensory process, memory processing, speed of cognition.

Dan Stickler: I mean, you name it, it's involved in some cognitive aspect but also in every motor aspect too.

Daniel S: Yeah. Choline is a precursor for acetylcholine. It's one of the key things. Also, in the liver as a lipotropic factor that processes fats and lots of other beneficial things.

You mentioned eggs and liver. What you think about lecithin? If someone wanted to do a basic supplement.

Dan Stickler: I'm not a big fan of lecithin. In general, I think there's some toxicities themselves to the lecithin on the gut lining. It is a toxin to the gut lining. I mean, low dose is typically okay, but too much lecithin can lead to some leaky gut issues in some people, it's not everybody. It really is a toxic substance to the enterocytes and you can get gap junction leaks and everything by abnormal reactions to the lecithin.

Daniel S: What are your thoughts on sourcing and its involvement in that?

Dan Stickler: Soy is the common source that we're going to run into with the lecithin. You have to wonder about that though. I mean, when you're talking about something that's such an isolated chemical or substance, how much contamination of the source are you going to get in that. I don't think it's that great of an issue. The soy lecithin itself like you heard me say earlier, I'm not a big fan of soy. People just tend to not react well to the lecithin and I don't think it matters whether it's a soy or something. I think it's more just related to the lecithin itself.

Daniel S: As far as getting into the natural supplementation, I won't dive into the topic now. Obviously, optimizing the acetylcholine pathway is the foundation of nootropics, so maybe next video we'll dive into that. That's everything from choline donors to acetyl donors to acetylcholine esterase inhibitors to the recetams that modulate the acetylcholine uptake, that whole thing.

Dan Stickler: One thing I do want to mention about the choline though is I run the genetics on people with their choline production. When I see deficiencies, especially in females that have had kids, I'll ask them if they had any problems breastfeeding because a newborn requires in the first couple weeks really high-dose choline in the breast milk. Women that had genetic variance don't produce as much choline.

Now, it's okay if they're supplementing with a multivitamin that has choline in it. They can generally get enough from that, but if they're not then they will be told that their baby is not thriving on the breast milk or that they need to supplement bottle feedings. Sure enough, I've had probably 30, 40% of the women that had choline variance that indicated reduction of choline that they had trouble, they were told that their breast milk wasn't helping their child, their newborn.

Daniel S: That's fascinating.

Dan Stickler: Yeah. I mean, all they needed to do was supplement with the choline and it probably would have taken care of the issue.

Daniel S: I think we are at time. We just got through some categories of nutrition for foundation of nutrients brain needs. We didn't get into microbiome yet. We didn't get into toxicity or other things, but it's a big topic. We had already tried to chunk it. Next time we'll still go to nootropics and smart drugs and then on to advance topics, but we might come back if you're open to it in the future and do say neuroinflammation and toxicity and microbiome and other things in the future.

Dan Stickler: That'd be cool, yeah. We can write a book on this stuff. You know that.

Daniel S: I'm down. I think that will be fun. Getting the program together of more advanced training for docs is the part that I'm most excited about so the people actually have resources to go to.

Dan Stickler: Yeah.

Daniel S: Everybody stay tuned. We're working on that. If you have any ways of helping, feel free to contact us. Then, this was fun. I'm looking forward to the next one, which we'll do and post soon. I'll try and get the links for the books that were mentioned in here and put them in the notes. Thank you very much for the time.

Dan Stickler: Thank you, it's wonderful.

Daniel S: This was fun.

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