Thoughts on ADHD, Metabolism, Genetics, and Diet…
So I’ve been challenged all my life by this undying curiosity of things, and how they work. I love diving into broken systems, discovering the connections, and testing hypotheses by just doing it.
Then, in early 2016, it was discovered that I have this genetic mutation which affects the production of the enzyme MTHFR. It turns out that not only do I have the mutation, I have one of the worse forms of it, of course.
So the programmer in me was driven to ask… what is the MTHFR enzyme? What does it do? What is it responsible for?
Looking at the above diagram, you see the MTHFR enzyme highlighted. As I’ve been LIVING in this world, I’ll build a bit of a narrative for you.
The MTHFR enzyme is the rate limiting enzyme in the the Folate Cycle. The Folate Cycle is all built around processing Folate (the naturally available version of Folic Acid) to THF, and then to Methylfolate. The Methylfolate is then used within the Methionine cycle to convert Homocysteine into Methionine. The other immediate exchange that occurs is the Methylfolate becomes THF once again.
Now when this process is gated, one of the immediately clear side-effects would be that more Homocysteine will be converted into Cysteine. Cysteine is one of the 16 non-essential amino acids … or, proteins, if you would rather. They’re non-essential because our amazing bodies have processes (what those in the field call “pathways”) for converting between them.
Now … our body doesn’t really have an intentional mechanic for dealing with excess protein so far as I can tell. From every indication I am able to suss out, excess protein effectively becomes “oxidative fodder” for other processes. So the world I envision here, is one where the excess protein in my system becomes slowly oxidized.
Interesting fact — while we need oxygen to survive, at a biological level, oxygen is poison! It’s stable, and it’s friendly! Fortunately, I’m good at absorbing the messaging shoved down my throat, and had ensured I included plenty of Calcium in my diet! Calcium, it seems, and Oxygen, will readily bond, with no other help from anything! Oxygen has 6 outer electrons, Calcium has 2. I bet the two get all lovey-dovey about an 8 electron shell. There’s a whole lot of math going on down in these depths… but anyway!
That’s right, Calcium will bond to Oxygen and protect you from it! GREAT! And the calcium is nice and non-reactive in general. Well. Mostly. See, as things get oxidized, they will likely also slowly get ionized.
Terminology… boy… that’s a big one. So. We’re going to segway for a minute…
Oxidization is the terminology used when a molecular compound has had a hydrogen atom exchanged for an oxygen atom. The molecular compound which has lost the oxygen is then said to have been reduced.
This very same process, when described in another way, is explained as followed:
Oxidization is a loss of electrons, reduction is a gain of electrons.
Ion, ionization, etc… it means an atom or molecule is negatively charged.
So deionized things are saturated in electrons, and ionized things are depleted of their electrons.
In so far as I can tell, this is the essential determining factor for if a material is considered useful by our bodies. Does it have electrons for us to use?
Ok — I think we’re caught up on terminology for the moment… back to the calcium.
It seems calcium… likes calcium. So the now ionized and oxidized cysteine, wrapped in calcium, starts floating around our bodies. But not just anywhere, no, not really. Because all of this oxidization happens within our cells. So the only way out is death. When cells die, they fall apart, and their bits are released into the interstitial fluid between the cells. Whatever the surrounding cells do not scavenge for themselves is eventually pushed into your lymph system.
The lymph system, it seems, does a pretty frightening double-duty. The thing we are all aware of, is that it is a large part of your endocrine system. Hormones are secreted into your lymph system to send long-range messages around the body. The other job is to get rid of now useless material.
That’s right, it’s combination biological postal service AND the cellular waste management service!
But what do you think happens, when this calcified, ionized, oxidized cysteine starts flowing into the lymph system? I suspect it starts to make a lot of friends. And slowly, these friends start blocking of segments of your lymph system.
This would then prevent areas of your body from receiving endocrine messages at the expected rate. It would also prevent the fat from those pathways from ever going anywhere else.
It … would make you … fat?
But doesn’t that … go in the face of everything we have ever been taught? I mean… SUGAR MAKES YOU FAT, RIGHT?! It’s the years and years of drinking sugar water that made me fat! EVERYONE KNOWS IT! … but here… here I have a pretty solid basis for a hypothesis which says that isn’t correct. And in fact, seems to suggest the opposite.
So I slowly start to pick things apart… there’s so many fronts, so if this is a little disjointed, I apologize. But the critical place to start, I feel, is energy.
If eating sugar isn’t what made me fat… and eating protein makes me fat… then maybe there’s another way to look at how I’m classifying my inputs, that will help me understand this all better.
So I dove down deep into metabolism, and I will try to summarize what I found, because I think it shows a fairly simple system that beats the hell out of the stupid dietary plate…
It all started with a question based on experiences I have had while undergoing treatment for ADHD, both intentional and incidental.
The first encounter I had with ADHD medication, was when I started a weight loss program, whose primary modality of operation was taking a stimulant and reducing all intake to liquids and protein, one small traditionally balanced meal a day.
The drug I was given is called Phentermine. You can see it’s shape here in the adjacent figure. I knew nothing of molecular structures at the time, but now… I find this drug very very interesting.
While on Phentermine, I excelled on multiple fronts. My relationship with my wife got better, I kicked ass at work, I contributed actively to my local user group, I gave conference talks. I felt alive, and for the first time felt like I could understand how anyone ever did anything other than go to work and go home and rest.
Then I took a break from the program for a while, gained weight, in retrospect, clearly got much more depressed and muddled. So I went and got myself a psychiatrist and got a prescription for Adderall.
Now the first few days of Adderall, at night, I would sit down, and just weep. I would cry and cry. The only thing I could express at the time, is it felt like it was from the joy and sadness around my now enabled mental state. I chocked it up to grieving for the life I could have had if I’d been treated sooner. I now see the event much differently, but that’s another post…
Adderall was absolutely transformative to me. The most concrete way I have ever found to describe ADHD is from my very first experience with the outside world after taking my very first dose of Adderall.
I walked into some craft store… JoAnne’s Fabrics, or similar, and I was on a mission. I had a thing I wanted to make, and I knew what I was looking for. I also knew this meant I was in for a long trip, because shopping, for me, as I had understood it at that point, was a very intensive process.
I say this now, because everything was different the moment I stepped into the store. Because … the world was no longer this expansive space of innumerable large number of individual things. I walked into an aisle, and all of the sudden, I could scan and determine if what I was looking for was present. Before, I would have to look at each thing to rule it out. Now… I could process collections of things.
But sure enough, eventually, the Adderall began causing anger problems. So it had to go. In comes Vyvance!
The Vyvance seemed to do really well. It carried me quite well for quite a while.
Unfortunately, for reasons I shall tactfully exclude, I lost the psychiatrist who prescribed me the Vyvance. The of the psychs he recommended I transition to, the one I followed up with, wanted instead to put me on some anti-psychotic which had reports of permanently changing brain chemistry — NO THANK YOU.
So I went on the hunt for a new psychologist all on my own, and found someone who specialized on ADHD in adults. Reiterating my life story, she has suspicions that I may have an underlying metabolic issue, and to ensure she doesn’t prescribe me something which harms more than it heals, I take a genetic test.
We discover two primary things:
- I have the double-whammy mutation of the MTHFR, meaning I only get 40–50% of the Methylfolate naturally that I should, and that then 50–60% more then available homocysteine will convert to cysteine instead of methionine.
- We discovered that the last medication I was placed on was very bad for my mental health.
Seeing no currently gating reason, I was placed back on Adderall to get a baseline for treatment with the new doctor. I also started taking Methylfolate as a vitamin suppliment, and found a “frufru” multivitamin which includes Methylfolate in addition to Folate. And about 14 days later… a great fog lifted.
The great fog lifted, and I could then see a very clear picture of what had just transpired over the last 6 months of my life. Looking back through it, seeing the stages of my mental health falling apart, my marriage shattered, my ability to work nearly broken beyond all repair… the crushing weight of it all. Of the magnitude of fuckupery that had transpired.
I cried, for what felt like… forever. Days. Weeks. I don’t even remember.
Over the next six to twelve months or so, I focus on trying to stabilize myself. Trying to bound my inputs and outputs. Where I consume energy, where I spend it. Lots of experiments with the inputs in innumerable combination, attempting to both find balance, and understand the levers that provide it.
I took a vacation at one point, went somewhere completely new, all expenses paid resort, all I had to do was relax. In the last few days, something changed in me physiologically. I can’t explain it any better than “it now took exponentially less effort to do anything.” It was like all of the resistance to anything was gone.
Once I got back though, slowly over time, I could feel this … urgency … building up. And I found that by taking “vacations” from the adderall, the urgency would go away. So the psych switched me to Evekeo. Evekeo, it seems, does not cause that similar sort of issue, for me.
Now, in order to show you the chemical difference between Adderall and Evekeo, we have to break down things a bit more.
Adderall is made up of two different types of amphetamine — Dextro, and Levo. The effective difference between them seems to be this: Dextroamphetamine seems to be able to cross the blood-brain barrier, while Levoamphetamine does not, or does so in lesser amounts — a point I have yet to be able to clarify.
Evekeo then has a stronger mix of bodily available amphetamine.
So I look at all of these structures, and I’m poking through wikipedia, and I stumble upon neuro metabolism, and how this thing called a trace amine is the rate limiter for neuro metabolism. Which drives me to make this:
I included Pseudoephedrine and Methamphetamine in the mix because … well … look at them!
And so if I pick this apart some more… why WOULD I like Evekeo more?
So it would suggest to me, looking at this, that maybe, what I don’t need, is more metabolism in my brain, but in my body! So how DO we make energy in our body? How does my mutated MTHFR impact it? Well, here’s what I’ve got so far…
Now, let me apologize, because that thing is a MESS, but … well ... welcome to the human body?
You can trace this all, and validate it, but the summary is this:
The human body seems to effectively have two power systems. I will delve into how they work below, but we’re going to start crossing modalities again, so it may get a little tricky.
From the outside, we have a few core inputs we require:
- Essential Vitamins (a.k.a. nutrients, as substrate for catabolic and anabolic reactions, and as targets for oxidative reactions, known as antioxidants)
- Essential Amino Acids (these are proteins, both fatty and not)
- Hydrogen (fuels some reactions, but most importantly, as water, soluble substances are dissolved into water, those substances are then free float around, thus enhancing the chances of spontaneous reactions)
- Carbon (Used to collect the Hydrogen into Methyl groups)
- Atmospheric Oxygen (O2) (To act as a source of electrons within an oxidative process when no better solution is around)
The first power system is the simplest. In the first step, it uses ATP (cellular potential energy) to convert Glucose (6C sugar ribosome) into 3C compounds, and produces 2 more ATP than you started with! This process is called Glycolysis. This process requires the following resources:
- NADH — Niacin (B3) based ADP structure
- FADH — Flavin (Riboflavin, B2) based ADP structure
That’s it for the simplest way to make ATP in the body. It consumes ATP and 6C ribosomes, and it produces ATP, Water, and 3C molecules. The NADH and FADH are recycled via the Citric Acid cycle, which we will talk about in just a moment here.
Now once we have these 3C compounds called pyruvate, or pyruvic acid, they’re sent into our cells, and the 3C compound is transformed into a 2C compound by a process called the Oxidative decarboxylation of pyruvate.
Oxidative decarboxylation of pyruvate turns the 3C pyruvate into 2C compound called Acetyl Coenzyme A, and in the process, recycles another NAD to NADH.
Finally we hit Oxidative phosphorylation, which takes NADH and Atmospheric Oxygen, and produces Water and ATP.
Now, this is a fairly simple process, but it’s intensive! The oxidation support required is tremendous. So to combat that, we have a secondary source of energy! Protein!
The way we process fatty acids, gives us a much less oxidatively stressful way to create power. Using an NADH and FADH, When you input a fatty acid, it pulls a 2C structure off of a fatty acid, skipping us right down to Oxidative phosphorylation. And as we have seen, recycling the NAD and FAD’s generally only requires resource availability of the nutrients needed.
So I have all of this in my head, and I go on vacation again, just doing what I do, and I come back… I haven’t CHANGED anything intentionally, but …. when I come back… I’m so much better.
Actually, to be fair, I’d gone pretty manic.
But I hadn’t changed anything! I kept taking my meds! I kept my behaviors as consistent as they could be. And then… a few dots began to connect.
When I go on vacation, I do change my behavior, if the circumstances are right. Because you see… when I stay in a hotel that has continental breakfast… I drink orange juice like water.
So I poked around at the idea more… and if you look at the chart and do the research yourself, you’ll find what I found: if your metabolism is busted, you’re also going to be hit when trying to even absorb any of these nutrients! And vitamin c, more specifically citric acid is critical in both recycling your NAD to NADH, which is one of the rate limiting controls to processing protein.
One last interesting note about NADH — the exchange that MTHFR performs? It requires an NADH to perform. So if you can’t recycle your NAD to NADH… well… you’ll just have to make more. But that’s going to be way out of line with what you’re going to get for natural resources. But what’s amazing about the question that makes me ask, this what I found:
Check out Caffeine! It looks a LOT like a piece of the NAD structure! There’s one other curious thing I can’t seem to trace down… the little scissor like carbon structures. Phentermine has one. THC has one with H3C’s attached. Topamax has two. Phenobarbital seems to have a potential one. I know I’ve seen them elsewhere too. Open to ideas there. May be nothing? Anyway … I need to wrap this up!
So when I go on vacation, I drink excessive vitamin c, which both works through the backlog of protein I have stored up from not creating enough Methylfolate, and I get additional support clearing out the old oxidative stress with the additional antioxidants.
Do not take stimulants and consume excessive amounts of Vitamin C if you value your connection to reality. That was a fun/scary day. I’d gotten it into my head that Vitamin C would fix it all, and drank … a lot of orange juice over an extended number of days. What put a stop to THAT was this experience:
I went to the bathroom, like normal. Flushed. Washed my hands. Flipped out the light before opening the door… and all the sudden, I couldn’t remember if I’d flushed. I thought it was odd as a one-off, but I found throughout the day… it was repeatable!
And at that same time, my mind was just racing. Big… expansive thoughts! Lots of the little connections that eventually lead to this post were formed. It was pretty crazy.
So that brings us to today. I see the body as a set of a few distinct metabolic systems. And I see metabolism as the physical process which enables the flow of electrons within our body, without killing us, like trying to pass an electrical current directly into our body tends to do.
I see mental and physical health as the expression of how well these metabolic cycles are operating, both independently, and in concert.
Because at the end of the day, it’s all about moving electrons. And moving electrons have a frequency. The frequency controls the speed at which a thing operates. So the body has to be in sync with itself, and the brain has to be in sync with itself, and then the body and the brain have to likely be within harmonic resonance from each other.
I believe the expression of mental illness comes from those frequencies being out of sync, and I now see the medications we prescribe, the food we eat, and the activities we engage in, as our levers to regulate our self-alignment.
I have a notion, that somewhere, buried in all of this, is a rubric which can be used to know when to prescribe which ADHD medication to a patient, based on gaining an understanding of their current metabolic imbalance.
But it has to be an integrated solution, because we eat and engage in lifestyle activities to compensate for biological imbalances. Drinking excessive amounts of alcohol triggers rapid cell death, which releases built up oxidative stressors. Listening to music is a form of biological meditation. It gives an external source to synchronize against. Pizza is my crack, because cheese and tomatoes are good sources of Vitamin C and Nicotine, and baked bread is an excellent source of Aceytl-Coenzyme A. So the diet I know is set up to accomodate my metabolic deficiencies.
More interestingly, I feel it would be fair to say, since introducing Methylfolate, I have been substantially less stable overall, but in my stable periods, I’ve been way more functional. But I’ve seen myself flip back and forth in behaviors, both for diet, and activities.
The MTHFR mutation meant I couldn’t methylate correctly. DNA Methylation is how we toggle gene expression. So if you cannot correctly toggle your DNA expression, the process of natural selection will get disrupted, and your body’s ability to repair itself will be impaired.
But thanks to the wonders of the human body… your genetics aren’t your destiny, they’re just the current state of things! See… every time your cells divide, they have to make a copy of your DNA. This is the simplest instance for mutations to be introduced, and the mechanic I see is wonderfully simple, taken from my own life: overwhelm or underwhelm required resources. DNA is made up of T, A, C, and G molecules. Cysteine is the C. The cysteine made because we couldn’t convert the homocysteine into methionine. So if you can affect the expected balance of TACG within the cell as it is copying, you can likely influence the result.
However, as you fix your inputs, very slowly, your body will be able to start experimenting again, toggling genes off and on, and what I suspect happens, is after I go long enough with a consistent set of inputs, my body is able to begin repairing, which shifts my requirements. But … I’m improving! So I become too terrified to change anything, because … it’s working! Right?!
But it isn’t working! Not any more! It worked. But now I’ve entered a new phase with new requirements.
So I think, to truly treat ADHD, we need to figure out which metabolisms need to be addressed, and tackle them with an understanding that EVERYTHING will change, over time.
What’s really funny, is now, reflecting on everything, I finally remember what it was that brought me to want to write in the first place.
I feel like when you break down the meds for ADHD (levoampheamine), their related “hard drug” forms (Methamphetamine) and the substances related to those (Pseudoephedrine), the differences are in balances of resources. CH3 groups are “readily available energy” — a simple reductive process away from being used. Ribosomes are “quickly available energy”. Nitrogenic compounds enhance cell death, which is promoting recycling of resources, and evolutionary cycles. Lone oxygen atoms, and oxygen bound with single hydrogen atoms, act as precursors for water to promote further stored resource usage. Look at Aspirin and Ibuprofen — they’re sugar, and precursors for water. I know it’s more complicated than that — two of the oxygens on aspirin are carboxyl groups, not free oxygen…
I feel like the rule seems to tease out to:
- If the patient has a solid nutritional foundation, and a well functioning lymph system, Adderall is probably to go to solution across the board, since it seems like it ends up with about the same amounts hitting the body and brain. I feel as though the anger problems I had on it were likely actually driven from a lack of resources to support the metabolic rate it drove. I was pretty unhealthy back then.
- If the patient does not have solid nutritional foundation, or their lymph system is having trouble (this is my new way of politely calling someone fat, I guess?) that ALSO needs to be addressed, WHILE addressing their baseline metabolic problem with traditional stimulants. I am fairly certain that calcified, oxidized cysteine builds up in the nooks and crannies of the lymph system, often settling in the head, causing the cranium to bulge. This is what I believe causes a further rift in brain/body metabolism, and I believe what has caused my recovery to be so difficult. Furthermore, I believe, to “think harder”, we scrunch our foreheads up, to create an excess of resources available to the blood/brain barrier, which creates the opportunity for the calcified bits to congregate and create new blockades. I feel this is the basis for what I now know as methylation markers. How do you treat this? Look at the other side of psychoactive drugs — the benzos, the anti-psychotics! Looking at them, where Amphetamines provide precursors for stimulants, benzos. And when you look at those, you see higher order nitrogenic compounds … fluorine, chlorine, sulfur, iodine. Cell killers. Lymph fluid promoters. Acidity creators. To loosen those calcium bonds, perhaps?
But more important than what this crazy lunatic thinks… what do you think? Is there anything to any of this?
