It’s an exciting time to be alive for genetic underperformers such as myself. As you will learn, we don’t need elite genetics to gain an edge in life. If we follow a few simple rules, we’re a long step in the right direction.
A brief introduction to genes as I learned from Professor Sapolsky in his book Behave.
A gene doesn’t decide when to be copied into RNA to create a protein that increases the number of serotonin receptors, the promoter does. Genes are transcribed (photocopied) into RNA by a promoter. There is a specific signal that precedes the RNA being copied from DNA. The old dogma was that a gene decided when it is turned on. A gene is like a recipe, and the old dogma is like saying a recipe decides when to bake a chocolate cake. Here’s how it works.
Transcription Factor (TF) > Promoter > DNA RNA > Protein, and the protein does a function.
The transcription factor (TF) decides when the promotor goes into the DNA to copy the blueprint into RNA to make a protein to do work. The question is, what signals the TF?
An example, if a mother smells her newborn baby, odorant molecules from the newborn actives receptors in the mother’s nose, which signals the transcription factor (TF) to copy the DNA recipe, creating the RNA, which in turn creates the protein enzymes that produce more oxytocin. More oxytocin promotes and transcribes the entire process again to activate milk letdown for the newborn. All this occurs from just a smell. I find that absolutely fascinating.
Another example, if blood glucose level drops fast or too low, TFs activate hypothalamic neurons that stimulate receptors in the nose that respond to the smell of food such as, “mmmm, hamburger!” So, we’re primed to eat. Genes are so cool!
What about muscle building? Well, testosterone binds to androgen receptors in muscles, this activates a cascade of TFs that increase protein synthesis enlarging the cell. What is TF? Muscle damage from lifting weights. However, without optimal hormesis and nutrition, not much muscle building will occur.
What about androgen thieves? Well, estrogen mimics such as microplastics and xenoestrogen, build too high signalling TFs that code for DNA building enzymes that create extra sex hormone-binding globulin SHBG, which binds to free testosterone and INACIVATES IT—like a swarm of locusts—super wasteful.
Another example of genes on performance is: Effect of caffeine on exercise performance.
A study was conducted of competitive male athletes (n =101) completing a 10 km cycling trial with the intake of either 0, 2, or 4 mg of caffeine per kilogram body mass. Individuals with the (A;A) genotype showed decreased cycling time by 3% (mean ± SEM) versus placebo. No effects were seen in individuals with the (A;C) genotype at any caffeine level.
However, athletes with the (C;C) genotype exhibited a 13.7% increase in cycling time. These results illustrate that equivalent amounts of caffeine may enhance performance in (A;A) individuals and diminish performance in (C;C) individuals. How well do you perform with caffeine?
- A:A = Slightly better performance, but not by much.
- A:C = No difference.
- Interestingly, C:C experienced a significant drop in performance.
As you can see, genes influence performance. Not only physical performance but antioxidant, detox, inflammation, and brain performance. If we supply gene fuel to all genes and enzymes, all our systems will be working. If we have slow genes, we can supply more gene fuel to speed them up. However, we can also increase their speed by getting our omega-6-3 ratio back to where our ancient genes and expect them to be.
Catechol-o’methyltransferase (COMT), this gene demands a lot of respect because it clears out dopamine, noradrenaline (norepinephrine), estrogen and its mimics, catechols and their mimics. Damn! This is a HUGE load and causes a lot of potential downstream issues if it’s not working or sleepy.
When this gene isn’t working it can cause catecholamine toxicity. Catecholamine toxicity is one reason why we need to keep this gene working.
- It destroys heart cells producing ‘infarct-like’ myocardial necrosis. R
- Similar to the brain but not full-blown necrosis, it kills brain cells, stress-induced norepinephrine, dopamine, and epinephrine (adrenaline) were toxic to neurons. R
Here are the vitamins needed to fuel this gene, including some up and downstream genes: Biopterin recycling (BH4) and optimal levels of NADPH (precursor B3), Iron, SAMe, B6, B2, magnesium, B1, vitamin C, copper, PQQ (redox factor) and PAPS (derivative of adenosine monophosphate that is phosphorylated at the 3′ position and has a sulphate group attached).
The three commonly known catechols are epinephrine (adrenaline), norepinephrine, and dopamine. However, here are some catechol mimics.
Coffee – having one too many cups of coffee could overload this gene because it’s slow/sleepy, lacking cofactors, estrogen is too high, or too many catechols coming in daily. So, the gene responds by going supernova, and people blame caffeine.
However, it’s likely the gene is coughing and spluttering because it’s overloaded and feeling jittery and anxious for no reason we blame caffeine, but it’s not caffeine in that situation.
More catechol sources:
Black tea, chocolate, and coffee have catechols, which can burden this gene.
Mimics, any compound having a catechol structure, like catechol-containing flavonoids, are targets of COMT and are capable of inhibiting enzyme function (either directly or through competition).
Some flavonoids include quercetin, rutin, luteolin, EGCG, and they’re in some fruits and veggies too.
If you’re not feeling good, you might want to consider that, well shit, my genes are overloaded—OR—my genes don’t have adequate fuel to keep them working—OR—I have a slow COMT gene—OR—I have an up or downstream gene issue.
Holy crap, what do I do? Read more here
Issue #1: COMT and overproduction of estrogen.
Having a fast COMT SNP is helpful because it’s clearing out estrogens fast, just don’t let it go to sleep, keep the gene fuel supplied to the gene so it can do its job. However, someone with a slow/sleepy COMT gene needs to be careful and might need to work with a coach or functional Dr to dial this in. Also, don’t forget that it’s clearing out catechols and its mimics, this will burden the gene.
Two more issues, the first is pain and inflammation. If your cells have above housekeeping levels of inflammation, or you’re like me before Jan 2018, you have pain that you just live with popping pain meds, the more pain, the more estrogen that’s produced, and it’s wasting your DHEA and testosterone:
As pictured above, when pain and or inflammation is high, it hyperactivates PGE2 (and PGE2 signals pain and inflammation), and PGE2 hyperactivates the aromatase enzyme producing an excess of estrogen. This becomes a positive feedback loop stimulating COX2 to produce more PGE2 (more pain and inflammation), and more and more estrogen – A Positive Feedback Loop.
In the introduction, I introduced the omega-6 metabolite arachidonic acid (AA), and how it’s super aggressive and acts like a swot team. In complete contrast, the omega-3 metabolite EPA is the resolver of inflammation and a powerful cell protector and healer.
Dr William Lands discovered in the ’70s that the omega-3 offspring, EPA, was at least 5-fold less potent as an anti-inflammatory and pain signal than arachidonic acid (AA), the omega-6.
It now comes down to simple math. If you have a high omega-6 ratio, say 20:1, then here is the problem:
Think about this, Dr William Lands discovered in the 70s:
- EPA slow the inflammatory reaction down by a factor of 5
- Current Government nutritional guidelines = 20/1 or HIGHER
- If you have a 1/1 ratio, you’re superhuman at a cellular level.
What this means is:
If your ratio is 20/1 or HIGHER, and knowing that AA is 5 times more potent as a pain/inflammation signal, let’s do the math:
5 x 20 = 100 more inflammatory and pain signalling and 100 times more likely to have alarm and avoidance and 100 times more likely to reach for pain meds.
The second issue: the more weight you carry, more specifically, the higher your body fat is, the more aromatase enzymes you have, meaning the more estrogen you’re making wasting DHEA and testosterone.
Issue #2: On a health kick slamming supplements could crash this gene.
Someone with a slow/sleepy COMT on a health kick might think green tea or EGCG is a good idea for fat loss or any number of COMT slowing agents outlined above. In five hours, they might feel like crap because lots of supplements and foods contain catechols that compete for metabolism by the COMT gene, so stress levels and inflammation are building, and the PFC goes offline. We have a great idea to have more coffee for a pick-me-up, but maybe that’s not a smart idea.
- Supply adequate vitamins and minerals
- Eliminate excessive stress as best we can
- Rebuild our cells with superior building materials, so they work faster and protect us from inflammation.
As I have mentioned before, my genes are certainly not elite; however, they now function as though I have elite genetics.
To your genetic success.