The Biochemistry of Laron Syndrome,
AND what to DO --- written for regular people.
Cells in our bodies take orders from other cells somewhere else. The communication is via substances.
It's not that different to any workplace, really, if people gave me an order AND a beer, I might be inclined to obey.
In the
Laron Syndrome situation, the orders have to do with growing. A chemical called Insulin-Like-Growth Factor ( IGF) is produced, binds to a receptor for I-G-F on target cells, and that sets up a chain of events.
The chain of events involve making protein and growing. As you might guess, that means MTORC1, our old friend, is involved up to his proverbial eyes. At least he would be, if everything were working properly.
But these Laron Syndrome people are 4 feet tall. Where's the Growth???
Obviously, there is a problem somewhere in the chain of command. It could be anywhere along the reaction sequence, but in the Laron population we know exactly the spot where things get messed up: it is in the
Receptor for IGF. And that receptor turns on MTORC1 downstream.
The Receptor is a protein.
That means there's a gene that makes it. And if it's messed up, you do not have to be a genius to guess that the
gene code has a mistake. What is that mistake? Who knows/cares. YOU cannot copy that in your life because YOU are not a mutant dwarf. ( That's a general statement, just in case, you
ahem actually
are a mutant dwarf, which is fine because that makes you a superior human.)
You CAN copy the effects downstream of the receptor instead.
This is how:
Additional investigation to gain insight into the “miraculous” combination of phenotypes exhibited in Laron Syndrome is ongoing. Rodent and Porcine models harboring GHR homolog knock out mutations also display dwarfism, decreased levels of serum IGF-I, increased longevity, and a lower predisposition to insulin resistance and cancer development, recapitulating some of the Laron Syndrome phenotypes3,4. Furthermore, as IGF-I levels can be modulated by diet and nutrition, Dr. Valter Longo believes that information obtained from research on Laron patients can eventually be used to generate a pill to prevent heart disease, cancer, and neurodegenerative diseases. He expects this within the next decade.
Want to wait for ten years to see IF the pill appears? Not me.
We can drop our IGF levels NOW.
The regulation of IGF-I by diet is complex. More than 20 years ago Thissen et al. showed that the plasma concentration of IGF-I drops steeply after a few days of fasting, due to the development of growth hormone (GH) resistance
What?? Starve for days??? Ok, Ok here is another way:
Fontana et al. [
38] persuaded six members of the Calorie Restriction Society to
reduce their protein intake from 24% to about 10% for three weeks. This resulted in plasma IGF-I falling from 194 ng/mL to 152 ng/mL. Therefore, protein restriction might be effective in reducing IGF-I.
Yeah. A Low Protein diet, specifically low in Leucine and Arginine is what it takes.
That means you have say Oatmeal and fruit, plus maybe a pineapple smoothie in almond milk for breakfast. NO WHEY. NO BCAA's.
It is not a hardship. In fact it tastes pretty good.
Run with a bean and tomato burrito for lunch, chips and hummus snack, and a vege dinner like some minestrone soup.
Get rid of meat, dairy, eggs & fish for
most of the meals you eat if you want to drop the IGF levels. Switch to light-medium endurance exercise to increase AMPK levels which inhibit MTORC1.
I ate my guts full everyday for 4 months, and averaged 5 pounds a month loss for 20 pounds cut. Easiest cut ever. BP dropped 20 points too. Cholesterol dropped too. So did inflammation markers. My CRP went down to 0.6 - yes,
ZERO point six.
I want to be practical here, because this is now going on to being a bona fide recommendation.
We NEED muscle as we age. It's OK to opt for a low protein diet most of the time in young adulthood, but people over 40 are losing mass, and need to work on keeping their muscle too. So periodically, I think we need to lift weights, and eat our protein, and stay strong, let us say for a 6 week stint? Maybe around Thanksgiving/Christmas, when there's a LOT of meat around, might be a good time for that.
But periodically, it's prudent to cut back, say for some weeks at a time, and just cruise along with
lighter endurance type exercise, and a
low protein-mostly plant intake. Lose a few pounds. Save a few bucks. Kill off some cancer cells.
The start of the year might be a good time for that, when everybody resolves to eat clean and lose weight.
How you organize it would be up to you. You could continue eating meat and just add in a couple interventions below, for instance. It wouldn't be as powerful, but there'd be benefit.
I just want to finish off with a list of cheap substances that block MTORC1, and will help suppress the bad stuff.
-
Curcumin and Black Pepper-
this breaks up MTORC1 into little broken bits, the most powerful intervention here.
Absolutely never
ever take this if you are building muscle. You will totally fail. While we are here, add on painkillers like Advil, Ibuprofen, Indomethacin, Olfen, Diclofenac, Ansaid, Aspirin, etc- all of those block the prostaglandin signal to build muscle and you will fail. All the interventions here would theoretically slow muscle gain, so you might want to watch them if your goal is to get mass back.
(Curcumin is in every form of Indian food. How many Olympic medals does India ever win? A billion people. Zero medals. Muscle growth inhibition. But what's going on with the
lifespan??) Anyway, guess what? That
same Curcumin is just as powerful at killing pain as all those expensive toxic pharmaceuticals, because they are hitting another similar biological pathway. So do a nice long run to drop your IGF and take the Curcumin after for the pain.
I get mine from Jamieson.
Don't buy Indian or Chinese Curcumin, they are putting Lead Chromate in it to make it look more yellow. POISON.
Jason Barron, you most likely think that's a great idea which is good for business, and who am I to stop you? Get yours anywhere you want!
- Epigallocatechin gallate -
Ok, forget pronouncing it. It's just
Green Tea, which tastes like muddy water.
Adding milk weakens the effect.
This is what you do- get yourself some nice Kenyan Black tea or English Breakfast, or Earl Grey ( Bergamot also kills cancer) or whatever you like, stick it in the cup with the Green Tea teabag. Brew both together, and you can get something drinkable.
Twinnings sells Green Tea with Peppermint. That isn't bad, just drink it without milk.
You need to hit MTORC1 every 4-6 hours with this suppressant. Not a hardship.
If you want to upgrade the power, use Matcha Tea.
https://medicalxpress.com/news/2018-08-matcha-green-tea-cancer-stem.html
They also found that the signaling pathways that promote cancer stem cells indicated that matcha "strongly affected mTOR signals, weakening components of the 40S ribosome." This raised the possibility that matcha could be used in place of chemical drugs such as rapamycin.
I'll be drinking that while the Pharmaceutical Industry comes up with the pill, and after they do, I'll still be drinking my tea.
-Fisetin-
Found in fruits, especially in Strawberries and Apples.
No hardship there. Soak em in strong salt water for ten minutes to neutralize the pesticides before you eat, and just rinse them off well in cold water first.
Fisetin, a natural flavonoid found in a variety of edible and medicinal plants, has been suggested to possess anti-tumor activity (
13,
22). Fisetin inhibits the proliferation, metastasis and invasiveness of lung cancer cells (
23,
24). A similar anti-tumor effect of fisetin has been observed in preclinical studies of colorectal cancer, prostate cancer, pancreatic cancer and melanoma (
25-
28), and it has been indicated that phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mechanistic target of rapamycin
(mTOR) may be the
target signaling pathway of fisetin
- Quercetin -
Found in Capers( yum) Red Onions, and to a lesser extent in things like cranberries. High concentrations in
Sorrel.
Quercetin blocks mTOR according to a German study, that says:
Several beneficial health effects are associated with the dietary uptake of this bioflavonoid, including alleviating effects on chronic inflammation and atherosclerosis. A variety of in vitro data indicate a possible use of quercetin for cancer treatment purposes through its interaction with multiple cancer-related pathways. Among these, recent data reveal that quercetin can inhibit mTOR activity in cancer cells. Inhibition of the mTOR signaling pathway by quercetin has directly been described
Just a brief note on Sorrel:
https://nutritionfacts.org/video/antioxidant-content-of-3139-foods/
It's a winner. By a country mile. You want this in your day, not just for the mTOR blockade.
- Sulphorophane -
Found in cruciferous vegetables like Cauliflower, Broccoli, Broccolini, Brussels Sprouts etc.
This compound is
potent. I'd rank it just below the Curcumin.
Look it up - you will be amazed at the chemistry.
It does not only work on mTOR, but has multiple powerful pathways that induce reversal of ageing, which I cannot go into here. We consume this stuff more than once a day,
everyday, here. One of the things it does is remove pro-carcinogenic particles in the bloodstream. Put it directly on a cancer cell culture, and it whacks them like it was a Big Pharma Toxic Chemo agent. Only, cheap, and without the toxic effect. Yeah. Your
blood becomes an anticancer agent when you eat the stuff.
Here, see for yourself:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4354933/
Chop up your veges raw, leave them for an hour or so, and THEN cook to get the max effect of the compound.
Curry the Broccoli with tumeric to get Curcumin into the dish for extra superpower. Stay away from the frozen stuff. They blanch it before freezing, and kill off the glucoraphanin enzyme that makes the sulforophane. There's a way around that but the post is already tooo long.
Again- just a reminder.
All these substances STOP effective muscle growth. If you are training for mass,
abstain from them during the process. Lift hard, Eat delicious Chicken Parmesan, and drink your whey every 6 hours. Your mTOR will skyrocket. Fuel your energy with something cheap and effective like potatoes or oats. Bear in mind the costs are including atheromatous disease, erectile dysfunction, kidney damage, enlarged heart, slowed cognition, neurodegenative diseases, etc.
But remember please, not to train like that for too long. If you are looking out for cancer, DON'T do it at all. Go with mobility/balance/endurance/skill or any other modality.
