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haidut

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Another great example of "synchronicity" (Synchronicity - Wikipedia) happened today. Two separate but related studies, with similar organisms, popped up today in my mailbox. One of them (at UCDavis) shows that the redox status in favor of oxidation, and thus high reactive oxygen species (ROS), can spur limb regeneration in tadpoles. The other one (at Tufts) showed that administering progesterone locally to the site of amputation for just 24 hours induces an actual limb regrowth over a period of 9 months. Unfortunately, I can't see much information on the progesterone dosage except that a solution containing a concentration of 500mcg/ml (0.05%) was used. This is quite low and most progesterone products on the market provide at least 1% or more, so pretty much any topical progesterone product should be able to replicate the design study.
Needless to say, the studies corroborate each other since progesterone is powerful pro-metabolic chemical that shifts the redox balance in favor of oxidation and increased ROS. The study with progesterone did not look into whether the effects of progesterone are due to increased ROS, but not many other plausible explanations are available.
Interestingly, the first study showed that if ROS levels are low then administering hydrogen peroxide H2O2 is sufficient to induce the limb regrowth. They used H2O2 topically and in low concentrations of about 50 uM/L. This is indeed not a very high amount as oral H2O2 protocols for cancer published on various websites typically call for 150mg H2O2 taken up to 4 times daily. The important thing to note is that the treatment in the study was for just 24 hours. Longer treatment resulted in interference with limb regeneration. And if people are wary of administering H2O2 (orally or topically), the same effects of increasing ROS (systemically) could probably be achieved by using low dose DHEA, as it has a very similar pro-ROS effects.
Low Dose DHEA Powerfully Shifts The Redox Status Towards Oxidation

Another interesting aspect of both studies is that the regeneration involves modulation of electrical currents, which supports the idea DNA is likely NOT the master controller of an organism's shape but the electrical fields this organism generates. In other words, both studies corroborate the idea of so-called morphogenetic fields, which Peat has mentioned and we have discussed previously on the forum.
Electrical Fields, Not Dna, May Shape The Look Of An Organism
Perhaps even more importantly, both studies recognize the role of the regeneration process in virtually all aspects of health and disease, especially degenerative disease like cancer. As Peat said, organisms with high regenerative potential do not develop cancer and quickly transform even transplanted cancer into healthy tissues. In light of the studies below, this can now be rephrased into "organisms with high metabolism do not develop cancer".
Adaptive substance, creative regeneration: Mainstream science, repression, and creativity
"...With aging, the regenerative process declines, and the process of tissue rebuilding slows. Against a background of reduced regenerative ability, tissue growth sometimes produces tumors, rather than renewed healthy tissue. When tumors are grafted onto the amputated tail stump of a salamander, which has good regenerative ability, the tumor is transformed into a tail, by its envirornment, or morphogenic field. The "cancer problem" is essentially the problem of understanding the organizing forces of the organism. The aging problem is another aspect of the same problem."

The first study clearly shows that redox status (i.e. metabolism) controls the morphogenetic fields. The more oxidized the state, the more easily the organism regrows limbs. So, in practical terms a combination of progesterone and DHEA (which Peat has been recommending recently) may be able to combine the design of both studies. I guess it would have to be rubbed on the amputation site, perhaps several times in a 24 period to ensure extended maintenance of the necessary concentrations used in the study. Depending on the specific health of the person trying this, if the progesterone/DHEA does not generate enough ROS by itself then adding uncouplers like methylene blue, higher dose aspirin, quinones, etc could help resolve any remaining issues with reduced redox status and insufficient ROS.

@Such_Saturation @aguilaroja

Early redox activities modulate <i>Xenopus</i> tail regeneration
Early bioelectric activities mediate redox-modulated regeneration
"...Reactive oxygen species (ROS) and electric currents modulate regeneration; however, the interplays between biochemical and biophysical signals during regeneration remain poorly understood. We investigate the interactions between redox and bioelectric activities during tail regeneration in Xenopus laevis tadpoles. We show that inhibition of NADPH oxidases-mediated production of ROS, or scavenging or blocking their diffusion into cells, impairs regeneration and consistently regulate the dynamics of membrane potential, transepithelial potential (TEP) and electric current densities (JI) during regeneration. Depletion of ROS mimics the altered TEP and JI observed in the non-regenerative refractory period. Short-term application of hydrogen peroxide (H2O2) rescues (from depleted ROS) and gains (from refractory period) regeneration, TEP increase and JI reversal. H2O2 is thereby necessary for and sufficient to induce regeneration and to regulate TEP and JI. Epistasis assays show that voltage-gated Na+ channels act downstream of H2O2 to modulate regeneration. Altogether, these results suggest a novel mechanism for regeneration via redox-bioelectric orchestration."

Exploring the Role of Redox and Bioelectric Players in Tissue Regeneration - Egghead

"...Regeneration of a lost limb is arguably one of the seven wonders of biology. While you can’t grow a new arm, a humble tadpole can grow a new tail in a week. Seeking a better understanding of limb regeneration, Min Zhao, professor of dermatology and ophthalmology at the University of California, Davis, and graduate student Fernando Ferreira (also at University of Minho, Portugal) are studying the relationship of redox players, like oxygen and hydrogen peroxide, with bioelectricity, including membrane potential and electric currents, to pinpoint how a tadpole can regrow an amputated tail."

"...“When we started this study we already knew – from decades old evidencethat electric currents were important for a successful regeneration, especially in amphibians; however, no evidence existed about ROS (reactive oxygen species) until very recently,” Zhao said. Ferreira used cutting edge technology, an optical based probe called the optrode, that allowed him to measure the flux of oxygen around a wound or amputation. Immediately after injury, oxygen enters the wounded area and fuels the generation of reactive oxygen species, including molecules such as hydrogen peroxide, creating a hypoxic environment, the researchers found. This stabilizes the activity of a molecule called hypoxia-inducible factor, which influences electric currents that control the movement of cells into the wound."

"...The research conducted by the team has one key and novel takeaway message: redox and bioelectric activities interact during the regeneration process. Tadpoles have a great capacity to regenerate, except during a well-defined period of metamorphosis. Interestingly, fine tuning of the redox and bioelectric states in this refractory period unleashes regeneration, opening hope that regeneration might be induced in mammals as well. The end goal for Zhao’s team is to be able to exploit redox and electric signals, perhaps by topical creams and eye drops, to enhance wound healing and regenerate damaged tissues."

https://www.cell.com/cell-reports/fulltext/S2211-1247(18)31573-0
Scientists Got Adult Frogs to Regrow Limbs. It's a Step Toward Human 'Regeneration' - D-brief
"...Millions of people live with amputated limbs that are gone forever. But that might not be the case in the future. For the first time, scientists have shown that adult frogs can regrow amputated legs. They say the approach can work in humans, too. “There is no reason that human bodies can’t regenerate,” said Tufts University biologist Michael Levin, who led the new research."

"...The trigger the team found is progesterone, the sex hormone involved in the female menstrual cycle, pregnancy and breastfeeding. The scientists applied the compound to frogs’ amputated back legs with a wearable bioreactor device for 24 hours. Then they watched as the limb regenerated. Frogs that did not receive the progesterone treatment developed cartilaginous spikes at the amputation site, whereas ones that wore the hormone delivering bioreactor for one day regrew a paddle-shaped appendage. Differences between the frogs were visible within a few weeks, Levin and team revealed today in the journal Cell Reports. Within about six months the regenerated limbs stopped growing, but the development had progressed to the point where under typical growth, fingers and toes appear. The regrown limbs had increased bone volume and density, bundles of well-organized nerve fibers and major blood vessels — all of which translated to frogs with regrown limbs that could move and swim with activity levels that were indistinguishable from frogs with intact legs. The research shows that spurring regeneration in vertebrate animals is possible and paves the way for similar work in mammals and eventually humans. “We may be able to induce the body to do what it does best, build complex organs,” Levin said. “The potential scope is huge.”
 
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tca300

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" In the 1950s a magazine article described the regeneration of a finger-tip when the wound was kept enclosed. Decades later, friends (one a child, the other a man in his forties) had accidental amputations of a finger-tip, down to the cuticle so that no visible nail remained. The boy's mother fitted his finger with the tube from a ballpoint pen, and the man used an aluminum cigar tube as his "bandage." Within a few weeks, their fingers had regenerated to their normal shape and length. I think the closed environment allows the healing tissues to be exposed to a high concentration of carbon dioxide, in equilibrium with the carbon dioxide in the capillaries, and to a humid atmosphere, regulated by the osmotic or vapor pressure of the living tissues. " - Ray Peat
 

ilikecats

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@tca300 wheres that from? It’s my first time reading it, very interesting. @haidut have you seen any reports of people regrowing finger tips with urea paste? I believe visionofstrength made the claim that that’s possible and it’s been done before but he never cited any studies or even any documented anecdotes. I always thought it was fascinating though.
 

tankasnowgod

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This is excellent, @haidut ! Wondering, do you think this has the potential to restore foreskin in those of us who have been circumcised? And do you you think the topical progesterone/DHEA combo would be best suited for that? I had the idea of using Androsterone and 11KDHT before with no results (although, I was very inconsistent with application). Maybe even a routine like Progesterone/DHEA topically in AM, Methelyene Blue in PM?

In addition to topical application, I would guess that all systemic efforts to raise metabolism would only improve results, or cut down time to see them. Thoughts?
 

haidut

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@tca300 wheres that from? It’s my first time reading it, very interesting. @haidut have you seen any reports of people regrowing finger tips with urea paste? I believe visionofstrength made the claim that that’s possible and it’s been done before but he never cited any studies or even any documented anecdotes. I always thought it was fascinating though.

I have not heard of urea paste reports but I have heard of reports about completely sealed fingers (as a result of high CO2) and also of partial regrowth under electrical stimulation with low frequency EMF. I think the urea can also work as it has similar effects to CO2.
 

haidut

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This is excellent, @haidut ! Wondering, do you think this has the potential to restore foreskin in those of us who have been circumcised? And do you you think the topical progesterone/DHEA combo would be best suited for that? I had the idea of using Androsterone and 11KDHT before with no results (although, I was very inconsistent with application). Maybe even a routine like Progesterone/DHEA topically in AM, Methelyene Blue in PM?

In addition to topical application, I would guess that all systemic efforts to raise metabolism would only improve results, or cut down time to see them. Thoughts?

I think progesterone/DHEA in a 1:1 ratio could be tried. I would not do higher than 1:1 ratio on the penis to avoid the anti-androgenic effect, but if you add some androsterone, or another strong androgen then probably 2:1 or even 3:1 raio can be used. Personally, I would first try a once daily dose of 10mg topically in 1:1 ratio, for 2-3 weeks. Skipping a day here and there probably won't matter much and if it works the effects should still be visible. The studies above said results were visible after 3-4 weeks but the full regrowth took 9 months in the frog case. Since you are not regrowing a bone then hopefully less time will be needed to see results.
 

Wagner83

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I wonder if all scars and tissues recover much better and faster if they are wrapped up properly.
 
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Fractality

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I wonder if a similar approach (prog/dhea) would regenerate damaged heart muscle or other organs?
 

haidut

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I wonder if a similar approach (prog/dhea) would regenerate damaged heart muscle or other organs?

Of course, that's probably the main reason Peat recommends progesterone for heart issues. Up until the 1970s progesterone was known as not so much the "female" hormone but as the most potent antifibrotic endogenous chemical in humans. Most organ failure is preceded by fibrosis, especially organs like heart, liver and kidneys.
 

Lilac

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" In the 1950s a magazine article described the regeneration of a finger-tip when the wound was kept enclosed. Decades later, friends (one a child, the other a man in his forties) had accidental amputations of a finger-tip, down to the cuticle so that no visible nail remained. The boy's mother fitted his finger with the tube from a ballpoint pen, and the man used an aluminum cigar tube as his "bandage." Within a few weeks, their fingers had regenerated to their normal shape and length. " - Ray Peat

Notice how Ray never brags? Nothing like "I read the article, and I told the people what to do and saved the day! Hurray for me!"
 

Fractality

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Of course, that's probably the main reason Peat recommends progesterone for heart issues. Up until the 1970s progesterone was known as not so much the "female" hormone but as the most potent antifibrotic endogenous chemical in humans. Most organ failure is preceded by fibrosis, especially organs like heart, liver and kidneys.

What about ischemic tissue? I didn't see any mention of that in RP's article.
 

haidut

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What about ischemic tissue? I didn't see any mention of that in RP's article.

Same. Ischemia is usually due to clots and progesterone thins the blood almost as well as aspirin. Not to mention it is cabonic anhydrase inhibitor so it increases CO2 and thus tissue oxygenation.
 

Fractality

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Same. Ischemia is usually due to clots and progesterone thins the blood almost as well as aspirin. Not to mention it is cabonic anhydrase inhibitor so it increases CO2 and thus tissue oxygenation.

Wow that's cool, the current medical standard belief is that once there is dead heart tissue, there is nothing that can be done.
 

haidut

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Wow that's cool, the current medical standard belief is that once there is dead heart tissue, there is nothing that can be done.

Peat has spoken about this many times, and of course disagrees. I have personally seen cases of complete reversal or end stage cirrhosis so it is quite obvious recovery is possible at least in cases of liver disease. There are published cases of reversal of heart failure as well, so that song being sang by doctors is just a bow to the organ transplant industry in return for some kind of kickbacks.
Leakiness, aging, and cancer
"...Saturated fats are protective against free radical damage and can reverse liver fibrosis. Thyroid hormone protects against excess estrogen, and can prevent or reverse fibrosis of the heart. Antiestrogens are widely effective against vascular leakage. Thyroid, progesterone, and testosterone are among the most effective natural antiestrogens, and they are curative in many conditions that involve vascular leakage. Progesterone and pregnenolone have been called the antifibromatic steroids, and it has been used to treat many inflammatory and fibrotic diseases, including cancer."
 

Cirion

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This is freakin' cool thanks for the post, very interesting. I am both surprised and not at the same time. I'm in the process of reading Nates' book F*** portion control and he talks in great lengths about the fact that the body actually trends towards health, not destruction, IF the building blocks are provided (hormones, good nutrition, etc). In that context, it makes perfect sense that the body can and will regrow even limbs given the right tools.

@tankasnowgod very cool man that you're considering the possibility of regrowth of the foreskin. I had not considered this possibility, but in light of regrowing limbs, why not? If you ever find something that works I would love to hear about it (You going to try the DHEA/progesterone combo out?), definitely post about your experience. I am also saddened that I was circumcised as a baby, and would love to find a way to regrow. There actually are methods out there that supposedly can regrow the foreskin (daily stretching) I tried those for a while but it was painful and tedious so I stopped. Some people have claimed to regrow the skin after as long as 3 years of this process, but manipulating hormones somehow seems like a smarter/easier/less painful method. I think the stretching method works because it also stimulates growth (but through stretching, not hormone manipulation), and also kind of provides a high CO2 environment because most of the stretching methods also provide an enclosure to the tip (so that is in line with covering the tip of a partially amputated finger) so it kind of makes sense how it could work that way. So maybe you will still need to cover it up as much as you can ("ManHood" company in canada sells things you can cover your tip with) I'm somewhat lucky in that I have SOME foreskin left, maybe 25% of it, so I think it's well in the realm of possibility for me to do so. If you find a way, it'll be a huge boon for alot of us guys!
 
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tankasnowgod

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I think progesterone/DHEA in a 1:1 ratio could be tried. I would not do higher than 1:1 ratio on the penis to avoid the anti-androgenic effect, but if you add some androsterone, or another strong androgen then probably 2:1 or even 3:1 raio can be used. Personally, I would first try a once daily dose of 10mg topically in 1:1 ratio, for 2-3 weeks. Skipping a day here and there probably won't matter much and if it works the effects should still be visible. The studies above said results were visible after 3-4 weeks but the full regrowth took 9 months in the frog case. Since you are not regrowing a bone then hopefully less time will be needed to see results.

Excellent! Just ordered some CortiNon, gonna give this a go.
 
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