In this episode, you will hear from biohacker Joe Cohen on how to biohacking your genes can help boost your health and energy levels.
In case, you’ve never heard the word “biohacker” before, don’t worry, this isn’t about installing computer chips in your brain or anything like that. It’s just about using technology to enhance your health. And specifically, in this episode, Joe is going to talk about how to biohack fatigue.
You will learn about
- What Joe believes are the root causes of fatigue
- What biohacking really is
- How to biohack fatigue
- A system of marijuana like molecules in your body and how it influences your energy levels
- The most important neurotransmitter in the brain for energy
- What the most important genes are when it comes to fatigue and energy levels
I highly recommend Joe’s SelfDecode service to analyze your genes. I use it myself. You can sign up here: Sign Up For SelfDecode HERE
(Note: That is my affiliate link for the service. I only endorse things I actually believe in, so my recommendation here stands whether or not you use my affiliate link. If you use it, I make a small commission, at no extra expense to you, so you’re helping to support the work I do — like bringing you interviews with people like Joe Cohen. But if you prefer not to support my work and use my affiliate link for any reason, feel free to go directly to his website www.selfdecode.com.)
WARNING: This episode has lots of technical science in it, and Joe presumes the listener has a solid understanding of physiology. If you do not have a solid background in studying health, you may find some of this interview difficult to understand. If you do have a strong background in studying health, you will likely enjoy this interview a lot. 🙂
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Watch the interview here
How to biohack fatigue and your genes, show notes.
How Joe biohacked his own body and overcome years of fatigue (1:35)
How root causes can vary from person to person (3:44)
How going through the process of finding your root causes can help you fix your challenges (5:59)
Why most tools for studying your genes can be confusing (7:13)
What biohacking actually is (9:38)
Why the limbic system has an influence on fatigue (12:17)
What the connection between the hypothalamus, lateral hypothalamus, and orexin is (15:10)
How fatigue can be caused by low hormones (17:10)
What the neural structure and neurotransmitters of fatigue are (17:48)
How the cannabinoid system influences the limbic system (19:12)
What the cannabinoid system really is and how to biohack fatigue with it (23:18)
The relationship between orexin and the endocannabinoid system (31:01)
How stress and anxiety decrease the endocannabinoid system (32:10)
How stress impact serotonin receptors (34:02)
How to biohack fatigue by lowering inflammation (35:08)
How high levels of ATP can keep your orexin system from shutting down (37:37)
How to biohack fatigue with exercise and why it is important for energy (38:14)
What light does to your body and energy levels (41:21)
What the most important genes are with relation to fatigue and energy levels (44:41)
How nicotine can support wakefulness (46:48)
How the adenosine gene can work against you (48:53)
How the P- genes influences your energy levels and mitochondrial health (50:53)
How an imbalanced endocannabinoid system can influence your weight (53:43)
How the circadian genes function and how they can cause fatigue (1:00:19)
What BDNF is, and how it helps you sleep better after exercise (1:02:11)
What Selfdecode is, and how you can use it to understand your health better (1:03:51)
So, let me read Joe's bio here on his website.
At the age of 25, Joe was sick broke and unemployable. Since biohacking himself from sickness in mid-2013, Joe has become an investor and entrepreneur, founding Selfhacked and Selfdecode. Selfdecode is your personal digital health coach that combines data from genetics, blood tests, and symptoms, to render personalized health recommendations.
Joe is the owner and main writer at Selfhacked.
Joe also consults with high-profile executives, self-hackers, and companies, and is writing a book about optimizing health.
So, with that said. Joe is there anything that I missed that you would like to add to that?
Joe Cohen: No. You pretty much got it.
Ari Whitten: Okay, cool.
Joe Cohen: You’ve got it all there.
Ari Whitten: Cool. So, you biohacked yourself in 2013, and you were sick, broke, and unemployed. Talk to me a little bit about that.
Joe Cohen: Yeah, basically, when in 2013 mean, I made a big breakthrough in mid-2013. But before that, I just had this a myriad of health issues starting from adolescence. So, as long as I can remember, at 13 already I was like, I’d eat something I’d get tired or I was just tired in the day. And then, as I got older, it started getting worse. But I was eating healthier, being healthier, I was mitigating a lot of it. And at the age of 24 and 25, it's just it just caught up with me.
It was ... I was trying some different diets, and I was actually trying high-fat diet and I did horrible. It caused, I had a meltdown from it.
Ari Whitten: Was this high fat Keto?
Joe Cohen: No, it wasn't keto and I don't want to necessarily dis high fat, guys because I do have a higher fat diet now. I wouldn't say it's as high as my experiment throughout, it's just trying to add fat to everything.
But, in and I do think you need a... It depends on the person's genes and things that. But, and there are states. I wasn't in the state where I was ready for that.
And so, basically, I was also eating foods that were - at the time I didn't even know it - but they were causing inflammation for me. And that combination of inflammation from food and just a mismatch in my lifestyle and diet and when I was supposed to be doing, it just caused...
And I was doing a lot of other things, I was going to school it, basically, caused me to flunk out of that semester. I just failed all my courses. I was... And then I was just, ”Damn, I need to fix myself here, this is, I can't let this... I’ve got to get to the root cause of everything.”
I was already reading on blogs and different things back then, trying to understand what was happening. But the issue is, that nobody was really telling you what the root causes. They would talk about the root cause and then maybe you'll say toxins, mold, or whatever it is...
If you don't understand the biological mechanisms, you're not going to understand what suits what person. Because one guy would be talking about mold, I won't say his name. But we all know who it is.
Ari Whitten: At least those of us familiar with biohacking.
Joe Cohen: Yeah. One guy’s talking about mold, and I’m looking at him and I’m saying, ”I really believe that mold is his issue. But how do I know it's my issue?”
Ari Whitten: Yeah.
Joe Cohen: The only way you can know... The only way you can know, okay who's the issue is what? Is to understand the nuts and bolts of the body, and then understand what's happening.
And so, I came to the realization that I’m not going to fix these problems by listening necessarily to broad recommendations. One guy will say, this one guy will say that. You need to have some mechanisms as well to know, ”okay you're sensitive to mold, and now I know why you're sensitive to mold. But I don't have these genes, or I don't have these symptoms that show that I have the same problems as you. What would help me?”
And that's when I started embarking on really understanding the differences between what the difference between me and let's say Dave Asprey. And now, actually, I could say after three and a half years of really being engrossed - I can tell you exactly what the biological differences are between me and Dave Asprey.
My system is built in XYZ way and I can go through the nuts and bolts, and I can, based on his symptoms and based on what I know about him, I can tell you what his system is. And then it is going to be different recommendations based on his system in my system.
Ari Whitten: Got ya. And so, through this process, you figured out what was going wrong with you and then you figured out how to fix it.
Joe Cohen: Yes, through this process I figured out the nuts and both of my system. Now I understand exactly from receptors, from the brain parts, from the physical parts, what is going on.
And I also tied it back into the lifestyle and dietary agents that may be problematic for these factors.
And once you understand the factors, or if you understand first what the agents are, you can also infer what the factors are, the nuts and bolts that are causing the issues.
Ari Whitten: Cool.
Joe Cohen: And also obviously your genes are able to help you once if you have an idea. Especially, if you have an idea. You can go both ways.
Number one is if you have an idea what the problem is you can start to look at your genes and say, ”Are any of these genes a problem?”
Number two is, you could look at your genes and say ”Huh, let's make sense maybe because I’m having all these symptoms.”
Ari Whitten: Got ya.
Joe Cohen: I was phase two. Phase one was Selfhacked... I first need to figure this out. And I would research something and I’d say, ”What, I might as well put this online!”
Ari Whitten: Yeah.
Joe Cohen: I did research and writing and then what I realized was, there's this whole genetic world exploding and we have all this information, but these tools that I was using were just beyond bad .it wasn't even bad, it was beyond bad. They weren't giving you information, it was a very tiny subset of genes, there's here's ten genes and absolutely no information, no references, and anything that they did give you...
I was just... This is complex the studies are actually less complex than what they're telling me because the studies at least give you a broad picture. They're giving you a slight snapshot, and this is just gibberish.
Ari Whitten: Yeah.
Joe Cohen: That's when I started to think about doing genetics. And so, I started... First, my idea was to build a program, to at least give people content that they can understand. Give them contents that they can understand. I kept on, okay, well we're only giving a thousand genes. I want to give all the genes. And then it got more complex, and then I'm, ”Okay, we need to simplify it, and then give it to people in different ways.”
So we've been working on this for about a year and a half, and we're building out a whole variety of tools that people can biohack fatigue and themselves in all manners.
More comprehensive, more curated content people understand it better, and also combine it with recommendations people know what to do with that information.
And also, you need to combine it with blood tests, symptoms, and another the health data like a symptom checklist, I can know what pathways in your body are not working. And based on that it's, ”okay, this pathway is not working we can compare it to your genes, there is a whole list of supplements for that pathway, if we want to make it this complete biohacking suite, where either biohackers, or other individuals, or functional medicine doctors can come and really understand what's going on, and also have targeted recommendations for individuals.
Ari Whitten: Beautiful. So, I want to get into that more the nuts and bolts around how genes interact with different lifestyle interventions, how that influences on specifically energy levels and fatigue, how it all ties in.
But real quick, just as a quick side point you have mentioned biohacking a couple of times. Obviously, you and I both know what that is, but not everybody knows what that is. Some people get scared off by that term, and some people think it's installing microchips into your body, and stuff like that.
So, can you just do a quick explanation of what biohacking is for people?
Joe Cohen: Well, I guess there's no standardized definition but I can give you what my take is on it. It's basically, it's basically, taking your health into your own hands to a certain extent, and it's it's using a broader set of tools than you would normally think of as, okay, the normal set of tools; you go to a doctor they either give you a drug or they don't. So, it's using a broader set of tools which includes lifestyle, diet supplements, or and for some people drugs as well, and testing it out on yourself and seeing how it works for you.
In my definition, I think there are smarter biohackers who will try to understand the issue first, and then unless they do this as a profession, like myself, where I just I feel I need to try everything. I don't necessarily recommend that to other people because you will get side effects. Especially if... I'll try high doses sometimes I'll do reckless things.
But, if you're just a consumer or someone who wants to just live a normal life, it makes sense you have a more targeted biohacking approach where you try things that have a higher probability of getting the results you want.
And the results of biohacking is to perform better and either the end results are you're happier your mood is better, you have more energy, you just can you let you get more out of life.
Ari Whitten: Yeah, for anyone that was scared off by the term biohacker, I just want to point out that if you are interested in using lifestyle strategies to improve your health, or your energy level, or your lifespan, you are a biohacker by this definition.
Joe Cohen: Exactly.
Ari Whitten: so, don't be scared off by that term. With that said and understanding your background, your frame of reference, and the approach paradigm that you take to this talk to me a little bit about the main causes of fatigue, and why somebody would be lacking energy.
Joe Cohen: Ok, yeah. So, with any issue that I come across, you want to look at a bigger picture first. Because if someone has fatigue and then they have eight other symptoms, then it's going to completely change the game, rather than if someone just has fatigue. I can tell you in my clients, I have a questionnaire and I give them a list of symptoms, and that allows me to see if a certain system is broken, and that I call the limbic system.
The limbic system is a group of organs in the brain. The hypothalamus, the thalamus, the amygdala, the cingulate, and the hippocampus. These are these are parts of the the limbic system.
The limbic system basically is your emotional system and it's also it's also very involved with wakefulness. You want to see if someone's limbic system is just off. If their limbic system is off then it's going to be a different set of reasons why they're fatigued.
I'll just give you a quick list of things how someone would know they have a limbic system problem.
So are they getting fatigued after meals number one and or chronic fatigue? Both of them can be a problem. Brain fog, how is their processing speed?
Do they also have anxiety?
Do they have OCD, or problems letting those thoughts, or thinking about the future too much?
Are they getting hypoglycemic?
Do they have gut problems?
Do they procrastinate a lot?
Do they have problems with motivation?
Do they have cold hands or feet?
And do they have poor deteriorating memory?
Inability to tolerate stress?
Low blood pressure?
And a lot of these people also feel tired but wired at night.
Those are some of the main clusters of symptoms that you see with people who have a deranged limbic system.
Now, the interesting thing is, actually, that...
So as part of the limbic system is very, the reason why it is a system is because it is very intertwined. And if one thing is not working the whole system can be out of whack.
The hypothalamus is going to connect to the hippocampus and everything is very interconnected. The center central part of the limbic system, I would say, are is in the hypothalamus - that's the central part - and in the hypothalamus, there's another central part it's called the lateral hypothalamus.
The whole hypothalamus is important. But I say it’s a relatively recent discovery that I haven't mentioned this anywhere is the lateral hypothalamus was actually the most important, and I knew about it for a while because I had a post on orexin.
You type in orexin, it's going to be a top, one of the top results on google. I wrote that post in 2014, actually, and the orexin system is based on a lot lateral hypothalamus. I realized orexin was matching up to all these symptoms.
Now, it turns out those at the lateral hypothalamus, which is the base for orexin, it basically interacts with all of these symptoms. Even cold hands or feet, gut problems. There's a connection there's a pretty direct connection between the lateral hypothalamus and all of these problems.
The answer is that to understand the mechanism fatigue, it's orexin is this peptide that is, basically, a neurotransmitter where you have this set of neuron in the lateral hypothalamus and the neurotransmitter is just a chemical that transmits signals from one neuron to another, in order to communicate. It's just an interneuron communication messenger.
If the lateral hypothalamus which is causing the communication, and the lateral hypothalamus is in case you have fatigue is not working and often there's a cluster of symptoms because it happens to me. The lateral hypothalamus is responsible for everything.
Now, if somebody just has fatigue, without all the rest of these issues, it means that it might not be a lateral hypothalamic issue it might just be that the person has a general mitochondrial issue.
They just don't have the energy.
It could just be there's a hormonal issue, they just have really low testosterone or really low pregnenolone or there could be something more specific going on. But if these cluster of symptoms that I spoke about, then it means that the lateral hypothalamus and the limbic system general is going to be impacted.
Then the question becomes for what causes of those issues?
Shall I go into that now?
Ari Whitten: Yeah, by all means. Unless you want to, I guess there's a point of divergence here. You can either go down more specifics on the limbic system or give more of an overview of the other potential causes. Wherever you want to go.
Joe Cohen: Well if I first wanted to go with just the neural structure and the neurotransmitters of fatigue. Just so people get a general understanding and how to contrast that maybe with other types of fatigue, that again if you just sent me an energy problem, or for example if the circadian rhythm.
If your if your circadian rhythm is completely messed up, and it might not be a problem necessarily in your lateral hypothalamus.
By the way, the circadian rhythm as it's a is based in the hypothalamus, in the suprachiasmatic nucleus. Those areas are very close together. The hypothalamus is a tiny part of the brain, and there's obviously communication there. But if someone's circadian rhythm is terrible, or if they're just not sleeping. Their sleep quality is terrible. It's obviously going to be a different problem.
They usually won't get necessarily the full cluster of other symptoms.
I think now the question is, ”well, what causes these limbic system problems?” And if I have to choose one area, one receptor or one system, it's more of a system instead of one particular receptor.
I would say, and this is I actually haven't told any non-clients this yet. I haven't really I haven't put it out that much. It is the cannabinoid system.
(If you want to know more about the cannabinoid system and how that causes fatigue, go read the article How Stress Causes Fatigue (Hint: It’s Not Just “Adrenal Fatigue”) and How To Eliminate Stress)
Ari Whitten: Ah, cool. I’m glad you brought that up because I saw your recent posts on that. I was going to ask you...
Joe Cohen: Exactly. My recent post. But it's hard to communicate everything in writing, I think this podcast is or webinars. If you get to talk about this, the interesting thing is nobody has ever mentioned really the cannabinoid system in any meaningful way and dealing with in these issues in general.
I mean, maybe they talk about pot or something, or pot can help you live in this way... Or CBD becomes big...
Ari Whitten: yeah, it is usually talked about in the context of just CBD... And what is cool about your recent article is you're talking about it there's this whole system, and there are lots of things that affect it. It's not just... It can be a CBD deficiency
Joe Cohen: Yeah exactly. You're not. It's not a CBD deficiency, although CBD can help the system in a variety of ways.
People don't even know exactly why CBD is working for people, they just say, ”Oh, it's good.” They see correlations. CBD... And it's interesting, but when you don't understand that the cannabinoid system is the root cause, CBD just becomes another supplement.
And also, I’m actually experimenting with the substance that I don't see anyone else taking because I understand the mechanisms, and I have only taken it one and it has a very interesting effect.
Ari Whitten: What’s that?
Joe Cohen: and I don't want to recommend, I could mention it here but I don't want to recommend it yet.
Ari Whitten: Well, It is too much of a teaser what you just said, all that without telling us what it is.
Joe Cohen: Okay. Beta-caryophyllene.
Ari Whitten: Never heard of it.
Joe Cohen: yeah it's the most, it's the only full agonist for the cb2 receptor. And the cb2 receptors is mainly non-psychoactive. It doesn't give you all those cannabinoid effects, but it's a very potent anti-inflammatory. And it's something that gave me very, very unique effects that were generally positive. And the question is, how dosing, sourcing the product, who should take this product?
And I don't want to give advice on that now.
Ari Whitten: Sure...
Joe Cohen: But I think that the interesting thing is in the research, there is only a few full agonist for the cb2 receptor the cannabinoid 2 receptor, and that's one of them. When they test it on the study this one is actually way more effective.
Talking about they'll use research chemicals and in order to see the full effect of things, but usually the research chemical is not something that [inaudible]. They usually have some synthetic chemical or some weird chemical that often caused a lot of side effects. That is the thing with Beta-caryophyllene.
I haven't researched a full side effect profile or anything like that. But what I do know is that it is found in a lot of plans and all spices pretty much. I know it's not necessarily going to kill me or anything like that.
Ari Whitten: Let me let me just interrupt you real quick if I can. I know that some people who maybe don't have a strong background in science probably feel overwhelmed right now with talk of CB receptors and cb1 cb2 and the endocannabinoid system. Can you zoom out for a minute and talk a little overview of what that system is all about? How can you use that to biohack fatigue?
Joe Cohen: Yeah, when I realized, you cannot compare... Once I was doing research on the cannabinoid system and the interesting thing is before I get into that, the reason I focused on the cannabinoid system is a few things; number one is, I was just reading passively about cannabinoid system here and there, there's this thing in my brain passing by, and one of the genes I found that was that one of my bad genes happens to be a cannabinoid one receptor gene.
For me, it was only two percent of the population has that variety. I said, ”Okay, this is relatively uncommon” and again, I knew what the cannabinoid system did and then I started looking at clients with that gene I realized most clients have that gene too and it you wouldn't predict it from just chance for anything, because it's not that common in the population.
Now, most clients would have one copy and that could cause some problem. I had two copies, so for me, it was way worse. That feeds into a call leptin sensitivity or just sensitivity to a lot of different agents.
Going into the cannabinoid system, one thing that I was researching was, ”Ok, where are these cannabinoid receptors most concentrated. Turns out, they're most concentrated in the limbic system, and the hypothalamus, even more in a lateral hypothalamus.
And the cannabinoid system and the orexin system are so intertwined, actually, which is something that again It's more of a relatively recent finding I haven't really discussed it too in-depth on the blog.
Basically, this whole paper does, I reckon that's the paper in the post, it's just talking about the interconnection between the cannabinoid and orexin system, and this [Inaudible] references and things like that.
Ari Whitten: okay
Joe Cohen: It is very, very intertwined and pretty much everything orexin does has an effect on, in some way on the cannabinoid system too. They're very closely it related. In the research, they will say there is a co-localization of these receptors, which means that these two receptors are found in the same neurons often. If you look at these functions of orexin, if you look at the functions of the cannabinoid, they happen to be very similar.
I’m giving one example of the Beta-caryophyllene that I noticed - and again I think it's a matter of dosing - the time that I took it... That night I was extremely awake and the interesting thing is... Normally, if I’m awake, and I don't get that much sleep the next day I feel crap. It's well, I’m not getting enough sleep I understand I’m not feeling great.
This time I got six hours of sleep, I didn't even notice at all. Zero. And that was a very interesting effect that I found. But it's something that, again, I have to experiment more with, I have to verify and see if, just to make sure.
The cb1 receptor is more psycho-activist cb2 receptors means the function is a potent anti-inflammatory.
Here's another thing was very interesting, the way the body works is a chain, is one connection goes to another connection. And we discuss orexin, is very intertwined with the cannabinoid system, and the cannabinoid system is very intertwined with the immune system, and the gut.
The people are also having immune system issues, and they're also having gut problems and things like that.
For example, something that I noticed is that I’m th1 th-17 dominant. What that means is there are T cells, there are kinds of lymphocytes, it's white blood cells, lymphocytes T-cells, T-helper-cells and certain subsets of T helper cells. [Inaudible] th1 and th17 is what I noticed is that I am th1 and th17 dominant, from which means that have high levels of these cells. And the most potent ways to suppress these cells is actually through the cannabinoid system. That's where the immune system meets the cannabinoid system, meets orexin, and they're all closely intertwined because as you know, inflammation inhibits orexin.
Ari Whitten: Right.
Joe Cohen: and again, orexin is closely tied with the cannabinoid system. Interestingly, actually, inflammation increases the cannabinoid receptors in order to counteract the inflammation.
That's how the body works. You have inflammation, the body says ”we need to take this down, let's increase the cannabinoid receptors” that they're more sensitive and that we can decrease inflammation. Which is interesting also, because for example, if I've been pretty strict with my diet for six months or something. Pretty decent I have breaks here and there, but what was interesting is, I kept it for six months.
That wasn't being healthy, I wasn't doing things that were with support my cannabinoid system.
And then I just said, ”let me just try, whatever, this thing that I know I will react to.”
I got such a strong reaction that I realized it was because my cannabinoid your system was not increased, where is let's say three and a half years ago, I would have eaten it, I had more problems, but I wouldn’t have noticed it as much. Because, again, the body can compensate.
[Inaudible] is inflammation it's going to increase the cannabinoid system, and my cannabinoid system, I just let the ball go and it wasn't and...
I'll give you one example of how I let the ball go. One thing that increases the cannabinoid system - there's actually a bunch of chemicals that or natural ways to increase it - one is butyrate. I stopped taking hi-maize or those kinds of things and those actually increase the cannabinoid system, the cb1 receptors. And a variety of other things that I was doing then was not increasing my receptors.
At the same time, I didn't have inflammation for a long time my cannabinoid receptors were low, Plus genetic susceptibilities, boom just complete chaos.
I was, ”Whoa! I've never felt this, I've never felt this tired, or it wasn't it was... I never felt so little motivation in the last year, or in the past three and a half years. That's something very interesting.
Okay, but getting back to it...
Ari Whitten: Real quick. The relationship of that the cannabinoid system to orexin, is is there is there a fairly simple relationship that can be summarized? Is there a direct effect of stimulating the cannabinoid system does so and so to the orexin? And can that help you biohack fatiue, directly?
Joe Cohen: Stimulating the cannabinoid system does stimulate orexin.
Ari Whitten: OK.
Joe Cohen: There is no simple... The other thing is, you might... It might be a little tricky because if you smoke pot you get tired. That's because of other reasons though, not because of orexin.
And I actually think that...I suspect that for example, you smoke pot at night you will go to sleep, generally speaking, most people go to sleep. You'll wake up feeling tired the next day. It's not improving the sleep quality in some ways, and some of that might be because orexin is being activated, it’s having a very significant impact in your circadian rhythm. It's causing phase delays in your circadian rhythm, and yeah... I think... But it does stimulate orexin.
Ari Whitten: OK. Got ya. Okay to zoom out... We're talking about causes of fatigue. First one limbic system issues, and then the second one I guess somewhat related to this still is the cannabinoid system.
Joe Cohen: Yeah, okay. That's also where... One day it feeds into one of the root cause of fatigue which would be anxiety or stress. If you're stressed out for a while, either acutely or chronically, it actually decreases the cannabinoid receptors.
Ari Whitten: Okay. So, stress and anxiety directly impact on the cannabinoid...
Joe Cohen: It directly decreases the cannabinoid receptors. It makes you less sensitive to the natural cannabinoids within your system.
Ari Whitten: How is that going to impact on energy levels and fatigue?
Joe Cohen: First of all, stress can kind of... If you have lower levels of orexin, again, orexin is going to is going to be responsible for motivation, cognitive function, memory, just all these things, or just energy.
The orexin, basically, impacts all these energy systems. If your orexin system is not functioning, if the lateral hypothalamus is not functioning, if the limbic system, in general, is not functioning, it will cause fatigue.
If you have excess anxiety or lots of stress it will feed into the orexin system, and it'll cause the reduction in your orexin system overall. And this is probably other... Other... For example, it's probably other mechanisms by which it can cause fatigue.
Another thing is I would say with stress is the impact on the serotonin receptors.r though there's 5-HT1A 5-HT2A, 5-HT2C.
Selfdecode has these genes actually. And the interesting thing is, again, I piece information from multiple threads. One day I’m reading something about the HTR2A gene - which is a serotonin receptor gene - and I’m reading...
”Wow, this has to do with chronic fatigue syndrome.” People with chronic fatigue syndrome more likely to have fatigue, more likely to have chronic fatigue syndrome. And actually, there is a connection between serotonin receptors and anxiety as well, and wakefulness as well.
I would say, I’m still looking into all the exact connections there, but there's definitely some effects when it comes to anxiety on the cannabinoid system, on the serotonin system. And yeah, I say that's what anxiety has to do with it.
Then inflammation is going to be another very significant cause. Inflammation is known in the research to just suppress orexin straight out.
Ari Whitten: Yeah.
Joe Cohen: Especially when the inflammation is combined with carbohydrates. I’m a believer that if you just take in carbohydrates you shouldn't be getting tired.
Ari Whitten: Yeah.
Joe Cohen: If you have some inflammation, or if you have mitochondrial issues, then you will get tired, you might get tired with inflammation.
I would say I’m a test case for that. We get extremely tired from small amounts of carbohydrates.
Ari Whitten: Still?
Joe Cohen: Even without any immune stimulants. Again for example...
Ari Whitten: Is that still the case, Joe? Or...
Joe Cohen: No. Not at all. No, I can have as many carbohydrates as I wanna, I don't get tires.
Ari Whitten: Okay good.
Joe Cohen: I mean, the point I... I have to be careful in the sense that I can't take carbohydrates that will cause inflammation for me. Because it happens to be that most of the foods of carbohydrates also have many immune stimulants. They're basically...
Carbohydrates are found in plants and plants contain the immune stimulants. So it's hard for people to differentiate, ”Am I getting tired from carbohydrates? Am I getting tired from the lectins and other immune stimulants in these foods?
I do fine with unlimited carbohydrates. I mean, there's a limit though because there is a very limited amount of carbohydrates I can eat. Basically, raw honey the only, and certain varieties of it, are the only type of carbohydrate that I don’t get fatigued from.
Ari Whitten: Wow.
Joe Cohen: Meaning that's the only one that doesn't have the immune stimulants that interact negatively with my body. If I want to eat a hundred grams of honey I can, but again, you don't want to eat 200 grams of honey. This doesn't work. I haven't tried higher limits, but I know, if I ate 50 grams of carbs when I was getting inflammation, I would be floored.
I even tried--- I'll tell you it was one point where I just tried five grams of glucose and I was well I’m really tired.
Ari Whitten: Wow.
Joe Cohen: That's nothing. So, yeah definitely... Carbohydrates, you have to look at again first principles, nuts, and bolts, what is going to call us with suppression of orexin. Carbohydrates, inflammation, and what's called, energy-related molecules in the hypothalamus – no, lateral hypothalamus.
They have done studies on this too with ATP. When there is ATP if you have enough energy in the lateral hypothalamus your brain... You will your orexin system will not shut down, even with when there is glucose present.
Now, if you don't have energy or there's inflammation, which will deplete the energy there, glucose will make you tired. That's why you have to look at the whole system. You have to see... Okay, somebody's getting tired, are they also getting inflammation? Do they have mitochondrial issues? Things like that.
And, something that you speak about and it's really important, exercise. If you're not exercising, you will have mitochondrial issues.
Ari Whitten: Yeah. Pretty much guaranteed.
Joe Cohen: Yeah. Exercise will stimulate all these genes that are important for energy production, things like that. And through that mechanism, that will, it'll help with your hormones, and things like that, it will reduce inflammation, and through these indirect mechanisms - many of them - exercise will help with energy production and being more awake for most people.
Now, there are some people who have exercise intolerance, different ball game, though.
Ari Whitten: Yeah. Okay, main causes give me give me the overview of the main causes that we've talked about so far. The limbic system, cannabinoid system, inflammation.
Joe Cohen: Yeah, let me break it up in letting me [Inaudible] it in different ways. One is, here in the brain is this fatigue happening, or within your neurotransmitters and that's the lateral hypothalamus, the general limbic system, and orexin. That is the main system, and histamine is another system within the brain but it feeds in very closely with an orexin.
Just to simplify, it is basically, orexin is the most important thing. And then the question is, what receptors or what pathways in the body are interacting with the system? By far the cannabinoid system is the most important and then you have other things as well Serotonin receptors, some things like that.
Then it's going to the general health, we're having a less inflammation but that gets into, what are... What would I say are the biggest causes of the orexin system and limbic system not working, or these receptors not working. And that is sleep a lot of people have sleep problems either they're not sleeping enough or their sleep quality is not great.
[Inaudible] and the other one was going to be inflammation, and an overactive nervous system, a lot of stress. Those are the root factors that are causing these biological factors to not work and I discussed inflammation why that causes fatigue.
Anxiety really destroys the cannabinoid system, and it can affect the serotonin receptors, and the circadian rhythm is very close to the lateral hypothalamus and that, again, linked very closely with wakefulness, and then sleep.
Now, there're other things, of course, that are very important. For example, you discussed light - the importance of light. Obviously, for example, light will increase orexin. It'll go through the suprachiasmatic nucleus from your eyes to the suprachiasmatic nucleus and again it will affect the whole hypothalamus, increase dopamine receptors, there's a drd2 receptor that your dopamine can help with wakefulness, modafinil increases dopamine, things like that. Amphetamines, dopaminergic, and on Selfdecode we have the drd2 receptor... Some people's receptors are not working that well, that feeds into fatigue and especially light aspect.
I hadn't seen... The thing is actually, something that's very interesting, is what how the sun interacts with the cannabinoid system in an indirect way... So when somebody is getting outside in the sun, getting light, the sun potently increases nitric oxide. And you can feel it if you haven't gotten sun in a long time. You go in the sun you get this burst of nitric oxide, and it is very relaxing.
Ari Whitten: Yeah.
Joe Cohen: That's what a burst of nitric oxide feels like, it has this sedating effect, and it increases blood flow throughout your body. Nitric oxide actually increases the cannabinoid receptors in a sense. Again, it's... Everything in the body is really interconnected.
In that sense, the sun can increase the cannabinoid receptors. I’m not sure if light directly can increase the cannabinoid receptors, but I know it increases the dopamine d2 receptors. And that again that will interact with wakefulness systems as well. No question at all.
Ari Whitten: The thing is that it's not all about mold.
Joe Cohen: No, that's exactly... But we do know that light does increase orexin so that would be how light would increase wakefulness. But if you're out in the light and you're getting sun, you're going to increase your dopamine d2 receptors, you're going to increase orexin, there's the nitric oxide, you're going to help your cannabinoid system. That's going to be really important.
I could put lack of light or lack of sun in causing these kinds of issues because of those pathways.
Ari Whitten: Yeah.
Joe Cohen: You talk about exercise. I would say exercise is just extremely diverse in what it can do. It's just doing a lot of little things that are helping, again.
Ari Whitten: Also stimulates the nitric oxide element.
Joe Cohen: It also stimulates, exactly. Increases blood flow, nitric oxide, all these things. And just a bunch of these mechanisms are going to help you in different ways.
Then nutrition as far as that it's going to be carbs. If your mitochondria are not working as well as they should, if you are having inflammation or stuff like that, or if you just keep tons of carbs.
Everybody's going to have a different carb tolerance for different reasons.
Ari Whitten: Right. Okay, I want to get into... More directly your wheelhouse around genetics. And I want people to really get this concept of how a gene analysis tool such as Selfdecode can actually translate into them doing certain things in their life, which positively impacts their life, or enhance their health or energy.
Talk to me a little bit about what are some of the most important genes. I know you've already mentioned a bunch of them, but can you just give me an overview of, maybe the top five, or ten genes along with what information they will get from analyzing them? And then how does that translate into maybe different interventions that can be used to benefit their life?
Joe Cohen: Yeah definitely. Basically, there's a... When it comes to fatigue there could be a variety of genes doing different things. But as far as the cannabinoids we have we have individual pages and different ways to view the information that an individual can look at.
You can also see if you have less common varieties of certain genes they'll pop up as red, and then you can click an information button and see what that means for you. It'll give you a real specific information for you.
For example, when I found the cannabinoid receptor one gene, there was one snp that was. We also give importance levels. One snp was, had a lot of research on it. And we'll give it a higher importance. CNR one it is called and then the CNT2 for the cannabinoid receptor two.
You want to see... Would be looking at... You can either look at individual genes or you can look at we combine genes or snps together in certain packs you can look at. It'll be circadian rhythm, sleep, things that.
I discussed the drd2. There's also nicotinic receptors that can interact wakefulness. For example, and also cognitive function as well. The nicotinic receptors also increase wakefulness as nicotine does. Nicotine increases orexin, it also increases the cannabinoid system through a variety of means which is very interesting.
I actually do well with nicotine, and I do well with it, obviously, increase wakefulness but we very interesting to see that it increases the cannabinoid system too.
Ari Whitten: Yeah, that is interesting. I've actually, as far as stimulants go, I’m much preferring nicotine to caffeine.
Joe Cohen: Yeah, for sure. Same here.
Ari Whitten: Just to clarify for people. I’m not talking about smoking cigarettes I’m talking about nicotine gum.
Joe Cohen: Yeah, yeah.
Ari Whitten: [Crosstalk] I just picturing me smoking cigarettes to get a stimulant effect from it.
Joe Cohen: Exactly. Yeah, I don't eat... Yeah, I don't need to smoke cigarettes. I mean, the harmful effects of cigarettes are, obviously, the toxins released from burning the tobacco.
Ari Whitten: Yeah.
Joe Cohen: That's almost all of it. Nicotine is not a pure saint. They're... Any drug, there is going to be some side effects. But pretty much, it's... There is way more benefits and drawbacks. But I do have a comprehensive post on that.
Nicotine and galantamine if you wanted to go that route, there are the alpha 7 and alpha 4 nicotinic receptors. And these are... These heavily influence wakefulness and working memory. And these.
There's a whole bunch of genes that I look at. There's, they are called CHRNA. And then there are three, five, seven.
You'd want to look at those genes in terms of, they might have... If you're having some working memory issues or wakefulness issues, some of those might have some effect.
Another one is a very interesting one is the ADA gene. The adenosine deaminase gene. It basically it's an enzyme that takes [Inaudible] and creates adenosine. Sorry, it takes adenosine and creates inosine. And when that... If it's not working that well, you're going to have a buildup of adenosine.
Ari Whitten: Yeah. Which is going to lead to fatigue.
Joe Cohen: Which is going to lead to fatigue, yeah. The way that the what another aspect of the fatigue system is when adenosine... Basically, as you burn energy throughout the day, adenosine builds up. And for a guy like me, adenosine is going to build up quicker because I’m not converting that adenosine to inosine.
Ari Whitten: Because of the activity of your ADA.
Joe Cohen: Yeah, it's lower activity, the end result of that and the studies are if people sleep less they're going to be more tired the next day. Because, again, they just have more adenosine in their system, they're probably going to be more tired in general, I mean.
But if your system is working, you're not going to be tired. We can't just blame fatigue on a gene, but it does have, it definitely is associated with cognitive performance and fatigue the next day, if you don't sleep well.
That was a very interesting gene that I found, and it's not that common. Five percent of the population will have one of those variations or five to ten percent. You might want to check that one, the ADA gene.
There are different fixes. For each gene that we have, we have fixes. How can you increase this gene? How can you decrease it? And what are natural ways? We have a variety different tools to see how you can modulate these genes.
Another one would be... This is actually a very popular one as far as athletic performance, is P-Delta. P- is actually one of the critical systems that differentiate between people. And in general, if we want to walk back a little, the nuclear receptors and the transcription factors - as they call them - it's just, transcription factors a gene that reads that causes the expression of a lot of other genes.
And these systems are going to have broad effects on the body, and this is one of the ways I categorize people as well. Different P-’s people will have either low or high levels and me to look at P-Alpha, P-Delta and P-Gamma those are the three main ones.
Then there's PGC 1 alpha or the genes called [inaudible]
Ari Whitten: And all of this tie into to mitochondrial health and mitochondrial biogenesis.
Joe Cohen: Yeah, exactly. Fat-burning, mitochondrial health, things like that, and just energy production in general. P-Gamma it's more anti-inflammatory and I have low levels. Bulletproof is going to have high levels of P-Gamma which means that if he takes in omega-6 he's going to gain weight because of Omega 6...
Ari Whitten: By the way, did you just refer to Dave Asprey as bulletproof?
Joe Cohen: Yeah, bulletproof.
Ari Whitten: Is that his name?
Joe Cohen: That's what I call him.
Ari Whitten: Cool! Ok, sorry go ahead.
Joe Cohen: he is a good guy to talk about because a lot of people know him, and he's very vocal about is his health history. You can, if you listen if you read about him, or whatever, you can see ”okay what is this guy talking about?” He has a lot of very specific recommendations, which I think are very suited for his biology.
For example, he will say our omega-6 is bad. The answer is, omega-6 actually can help activate the cannabinoid system and it also help activate P-Gamma, And I was thinking, I don't do that badly with omega-6, I actually think I do pretty well.
Ari Whitten: Yeah, I think the same. I mean, I went through... Many years ago I went through a phase where I was avoiding them like the plague and I thought that omega-6s were the devil. But now I actually eat quite a lot of nuts and seeds and I find that I react very well to them.
Joe Cohen: Yeah, exactly. And for me, I mean I I react to most plant-based foods. I don't do well with nuts and seeds, but if I just take the oils, I mean, I generally don't I don't react negatively to them. And in general more positive. The reason for me is because I have lower P-Gamma, lower cannabinoid system - and by the way part of the cannabinoid system, again they're also very interconnected - the cannabinoid system actually activates P-Gamma. It’s this whole web and to both the cannabinoid and the P-Gamma cause increased waking.
When they give people something to block the cannabinoid receptors, they lose weight, and again that's why it's part of it a lot of my clients tells me, ”I can't gain weight.” And the answer, ”You're never going to gain weight if your cannabinoid system is not working.” And they don't understand, they don't understand the in-depth mechanism.
What I could say is it, obviously, if you can't gain weight and you're having these limbic system problems, I can tell you for sure your cannabinoid system broken. Whereas somebody... Then you have these people who say I can't lose weight and that's obviously also a very large section of people the question is, why are these people different? How are they different? One person is saying I can't I can't gain weight, one person is saying I can't lose weight.
It has to do with the P-Gamma and the cannabinoid system.
Yeah... Basically... Yeah... Let's see where are we going... As far as people in... And these are also anti-inflammatory systems. What I noticed is when people are... When it's easy for people to gain weight, those people generally have less issues with inflammation in a lot of ways, which was a very interesting thing that I realized early on. I just didn't understand why.
That has to do with P-Gamma, a lot of it has to do with P-Gamma. Again, the cannabinoid system and you can check for routines with P-Gamma, you can check for genes for P-Delta, P-Alpha, and a lot of these transcription factors actually compete with one another. If you have high levels of P-Delta and it will compete with the other one, the other P-s in general.
What will increase generally in all of them, is the PGC-1-Alpha and that will help mitochondrial function. That's something that generally everybody does well with, but there are genes for that, there are genes for the other P-s as I said. Now, P-Delta is that... Those they found that some P-Delta genes, you're eight times more likely to be an extreme athlete, or perform better at athletics, and things like that.
That's because it helps with energy production and stuff like that.
Ari Whitten: By the way, on that note, there was a compound that I was interested in called [Inaudible] [crosstalk].
Joe Cohen: I have a post on that, actually, I think.
Ari Whitten: Yeah I saw it... It looks to me it has some really fascinating effects and I do see quite a lot of people taking it.
Joe Cohen: But there are risks.
Ari Whitten: Yeah, but then there's the cancer issue and that's what has stopped me from taking it. But I’m very curious about how somebody with fatigue due to mitochondrial dysfunction would do with something like that.
Joe Cohen: That's, I mean, that's an interesting question. I think with fatigue for mitochondrial function they'll want to focus on the PGC1Alpha. Really going selective with the P-Delta is going to crowd out some other things, that again gets to P-... For example, if your P-Delta dominant you're going to crowd out the P-gamma, P-Alpha and those are also really beneficial.
What happens with P-Delta is more specific for athletic performance and things like that. And I can't imagine that some negative side effects will occur.
Kind of the same with the cannabinoid system, it's not, there's no such thing as one thing that's just great all around generally speaking. The fact that I had lower cannabinoid system allowed me to be very muscular without really working out. And also, again, it also interacts with AMPK. P-Gamma is going to interact with AMPK and SIRT1 which is the energy production pathways and mitochondrial enhancement pathways.
For example, people won’t know it, but with SIRT1 and the AMPK can actually give it to P-Gamma.
Ari Whitten: Oh, interesting.
Joe Cohen: And some people can have higher levels of that... And that was interesting too because I noticed that had some genes that were associated with higher sirt1, which was very interesting because I’m ”Well, SIRT1 is great. Why am I still having... Why am I genetically not able to, whatever eat, normal food ?” And the answer is that that pathway can actually inhibit the anti-inflammatory P-Gamma pathway.
Ari Whitten: Interesting.
Joe Cohen: So, yeah.
Ari Whitten: Give me maybe three more genes
Joe Cohen: Again, there are the sirts. The SIRT1, SIRT3. Those are going to have to do with energy production and PSR1, actually, is a gene that has to... It’s associated with high-orexin. Again, you want to see, what your snps are there.
There is PDE4D gene. Which is, again, if you have high levels of that it can cause decreased cyclic AMP and that can cause decreased energy and fatigue. They found that PDE4 inhibitors can increase wakefulness after fatigue... Yes, there's something... Whether it is sleeping less. So, that's something that's going to have to do with wakefulness.
The adrenergic receptors, the beta and alpha adrenergic receptors, are going to have to do with fatigue and also keen to related to athletic performance as well. It is kind of, how your adrenaline system is working, and that's also going to feed into a fat burning system. But might not be good in some other ways. It's going to contribute to activation of your nervous system. But that's ADRA2A and ADRB1.
Then there are circadian genes. Again, the circadian rhythm really interacts with the wakefulness system, it has to... Actually, in the sleep research, the researchers believe there are two systems. There is the circadian system and there's a one is a build-up system where adenosine is building up. And you're getting more and more tired, but then there's this circadian wakefulness system that's stopping you from going to sleep. And but then all of a sudden that drops off at a certain time if your circadian rhythm... And then you get really tired.
Ari Whitten: It allows adenosine to hit you.
Joe Cohen: Exactly, exactly. It allows the adenosine to hit you. It's this wakefulness system.. The circadian rhythm definitely interacts with the whole orexin and wakefulness system it has to. Looking at your circadian rhythm genes, sometimes you'll see different genes for that, different people will do well... Will do poorly with circadian rhythm stuff because of those genes. Those genes...
We have in our snp analyzer we have packs. You can look at whole packs and it'll give you genes associated with different issues. We also have a search feature, now, we have in the database you can do disease... You can pick a disease and if you do all the genes and snps related to that disease.
But if you want me to just name you a couple it would be pers PER3, PER2, PER1, which stands for period which is part of the circadian system, as well as clock genes. These are going to be important for the circadian system as well. Something that I think is really important also for sleep quality is BDNF gene. BDNF is actually part of the reason why exercise helps you sleep better, and with wakefulness in general.
Again, exercise kind of that indirect thing often has all these indirect actions. It'll increase metabolism, increased energy buildup during the day which will help increase your sleep quality, exercise will also... Yeah like you said, with some nitric oxide. So, all these indirect pathways. But the most important for sleep is that it increases BDNF
Ari Whitten: And tell people what BDNF is just they know.
Joe Cohen: BDNF is this neurotrophic, it's just basically steroids... Neurotransmitter steroids for the brain. A neuropeptide that increases the growth of neurons and it does a lot of other the things in the body as well. It increases metabolism, it's associated with weight loss and things like that. That's why through the BDNF pathway you're going to have a lot of different effects. For example, people with certain genes, certain variations they have less... I actually have one of those... My sleep quality is not going to be as good. So, that may seem more... That and the ADAA gene is definitely contributing to my need for more sleep, or just seven and a half - eight hours, which is people these days don’t want to get.
Ari Whitten: Yeah, sure. Cool I mean, you just gave it a ton of different stuff. But just to recap and summarize so people can grasp all of this stuff that you just went over. Basically, there are these different genes that they will have, kind of varying degrees of. They may have good variations of that particular gene, or not good variations when it comes to circadian rhythm genes, or genes associated with AMPK and the P-s and pgc-1 alpha and mitochondrial function, and the ability of mitochondria to produce energy, BDNF, the sirts, all of these different layers, and if you go into Selfdecode, what happens from there?
Joe Cohen: Okay. There are a few ways you can find stuff from Selfdecode. Number one is, if there's any gene you want to look at, you can go to... Once you have your stuff uploaded you can just go to, selfdecode.com/gene/ you just put the gene name in.
Now, for some of them it'll be you know clock it'll be pretty it'll be fine but genes actually have different names and not always will it click, but it's stuff ADA, P-D, BDNF will actually work. PRD2 will work. So. A lot of them will work - not all of them will work - but we do have a search feature that you can search for the genes.
You could also you can search for them in this reporting system. Which... There are a few different ways of few different search features you can do in the system. But beyond that, there's a snp analyzer. What we call a snp analyzer that groups the snps together in different ways. In addition, there's different gene packs that we put together that, for example, I'll have my ”Joe’s favorite genes” if you click on ”Joe's favorite genes”, it will have a lot of... It will have the genes that I mentioned here, for example.
But we have different categories of genes. Let's say for neurotransmitters, that's a different way you can look at it. The other way is... Yeah, and then, within the system, you can look at there's a feature that will give you a list of your bad snps. And then while you're looking around, you can bookmark the snps.
We also have a recommendation system which we, basically, scan through all the potentially problematic genes and then we say ”Okay, these are the potential problematic genes.” We have a massive database of chemicals, and we categorize them as whether it's beneficial, natural, and you can see the beneficial, natural, substances that interact with your genes. And then, if you look at that you could say, ”Oh, this is interesting I should do more research on this chemical and see does it make sense for my biology?”
And you can also click on the ”see interactions” and they'll show you all the genes that it's interacting with, and you can just click on the gene. We're implementing a whole bunch of new systems that constantly make it simpler. For example, once one small thing is... Right now, you could click on the genes but something that relatively simple to do is show you show you whether each chemical is increasing a certain gene, or decreasing a certain gene, within the picture. Then you have this broad picture you see ”sod2 increasing.”
That's something that we're constantly making it more simple for somebody to upload their genes. And then just, and also we're making it, we're making the recommendation system way more accurate by including symptoms. Now, we're working on systems that include other things; symptoms, blood tests, and pathways.
Basically, I give you a checklist, you check out, you check things off, and then will I can figure out which pathways are not working and we can weigh that into the recommendations. Same with genes, and we can... Another thing is, we can we... Have to once we weigh a lot of more a lot more factors, it's going to, basically, keep on getting more accurate. Now, it's still good in the sense that you can look at it and say, ”ah that's an interesting, let me explore this a lot more.” And it's gonna... It's that substance to interact with most of your genes the most number of genes that might be problematic. That’s... Looking at the recommendation system.
It also gives you toxins to stay away from. You can also... There's also a recommendation system for if you're concerned about a certain disease, let's say whatever it is, you can type it in we have a whole disease database and they'll give you all the snps related to that disease all the genes. You can click on all the snps, all the genes, it'll show you which one... Which variations are risky, which ones are less common. They'll give you, and then you can see all the chemicals that have the most interaction with those diseases.
You can do... You can search for a given disease or you can search for just, in general, you know what do my genes have to say about your all my genes but which chemical beneficial chemical interactions most my genes? If you're looking for something specific, you want to look at more a gene pack where we categorize genes by a certain category. [crosstalk]
Ari Whitten: I've actually been in there. I mean I've seen you have packs related to, for example, detoxification and you'll rank somebody like... How do your genes deal with various toxins? How do you do with methylation? The exact supplement for methylation. How are you as far as your propensity for a fat gain? You know...
Joe Cohen: Exactly. We have... Yeah, exactly. Those are part of the snp analyzers. We actually have a few different. One pack is just giving you genes, and one pack is giving you grades and maybe conclusions. Now, we are working on making that system more accurate, but at the very least, you're getting some idea, and you're also getting a list of snps and genes are associated with those kinds of things. You can click on the individual one and just if something... If you want to explore something more, we give you the tools to do that. That's a good thing...
Ari Whitten: Nice, awesome. Yes well thank you much this has been a pleasure chatting with you and I also want to mention the people I've been into Selfdecode, I bought it myself, and it's phenomenal. I highly recommend that you go do that, thank you, Joe, it's been an absolute pleasure talking to you and thanks for sharing much interesting ideas around how to improve your energy levels.
Joe Cohen: Awesome. Yeah, was great talking to you.
Ari Whitten: Yeah likewise.