Restoration of GULO functionality in humans?

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Restoration of GULO functionality in humans?

Post Number:#1  Post by whitenoise » Thu Oct 11, 2018 7:59 am

Hi guys,

This has been asked before, but if not I thought I would throw this idea out. Do you know whether someone out there there is research going on to restore the Vitamin C GULO defect in humans? I've read about a couple of succesful experiments in guniea pigs, but no-one appears to taking the next step. I'm no chemist, scientist or biologist, but couldn't some time of 'project' or research group be setup from intelligent, liked-minded individuals with this goal in mind? A evaluation of the current research, some funding (possibly from kickstarter or some other crowd funding project) be at least a start to this idea?

Now this would be all quite controversial, since should this 'project' be successful, then this would have massive ramifications on many industries and the general public. That scene from the film 'Chain Reaction' comes to mind where the key to making cheap, clean electricity from hydrogen (sea water) is discovered and before this 'secret' is posted on the internet the inventors are mostly murdered by the CIA. Yes its a film and its all fiction, but I'm sure someone like this would not be tolerated well by the powers that be.

I'd be interested to know what people think? Is this all a pipe dream? Unfeasible? Or would it take the right set of individuals/circumstances to at least start on this quest?

Oh and I've just realised this is my first post here, so I guess I should say hello! Perhaps a bit deep for my first post! ;)

Some examples I mentioned:
https://www.ncbi.nlm.nih.gov/pubmed/18764764
https://www.ncbi.nlm.nih.gov/pubmed/14962674
https://evolutionnews.org/2013/08/a_simple_propos/
https://adc.bmj.com/content/archdischil ... 8.full.pdf

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Re: Restoration of GULO functionality in humans?

Post Number:#2  Post by pamojja » Sat Oct 13, 2018 3:43 pm

Welcome whitenoise,



Interesting paper. The first time I heard a thesis why the GULU gene silenced in humans:

Considerable controversy exists over the role of ascorbic acid in maintaining health and resisting a wide variety of diseases including cancer. It has been contended that the evolutionary loss of ascorbic acid synthesis capability in man has enhanced the occurrence of numerous chronic diseases and was essentially a maladaptive alteration which initially was well tolerated because early man lived in a habitat which supplied foods with amounts of vitamin C equivalent to what they normally may have synthesized. However, as humans migrated into habitats with less availability of vitamin C, the adverse aspects of the loss of ascorbic acid synthesizing capability came to be demonstrated (1,2). In contrast, this paper proposes that the loss of an ability to synthesize ascorbic acid in humans, far from being a neutral or totally negative mutation, may have been a critical preadaptation which markedly enhanced the survival of early man with a G-6-PD deficiency living in a malarial infested environment. [emphasis added]

What survival advantage might this have imparted? The paper explains,

It is proposed that the loss of ability by humans to synthesize ascorbic acid may have markedly enhanced the survival opportunities of early man living in a malarial infested environment. This hypothesis is based on biomedical evidence which indicates that glucose-6-phosphate dehydrogenase (G-6-PD) deficient individuals display enhanced sensitivity to ascorbic acid induced hemolysis which has been fatal at sufficiently hiqh doses and that the G-6-PD deficient trait has been selected for in malarial environments.


Makes completely sense to someone like me who almost died from 7 malaria fits.

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Re: Restoration of GULO functionality in humans?

Post Number:#3  Post by ofonorow » Mon Oct 15, 2018 2:38 pm

Good post(s) !

I wish Van Carmen was still with us. He was a joy. Van was convinced (among other ideas) that the spice cinnamon mimimic'd the missing 4th enzyme needed to produce ascorbate out of glucose. (The enzyme that is missing because of the GULO defect. Genes code for proteins. Enzymes are proteins).

His idea was that you could live without vitamin C if you took cinnamon. (I hope that experiment isn't the reason he is no longer contributing at the forum :(

But the eventual answer is to revive the GULO gene to its pre-defect/mutation state. If the mutation is fixed in the mother's egg, than all descendants would have the correct gene. There is probably no way to change all of our cells, or the liver cells where it matters, etc. So any fix will be in the egg (or zygote - to account for father's contribution.)

So what is the "correct" gene - genes can be long strings of nucleic acids...

From a forum that discussed GULO among geneticists, after the genome was mapped, we learned that our GULO defect is ancient, and that different primates (without the ability to make ascorbate) had many variations. I think the estimate was that humans first lost the ability about 3 million years ago, so there may have been mutations on the mutation. Further mutations would have no evolutionary effect (unless it accidentally activated the GULO gene) so the question of what the "correct" gene looks like is open.

A little birdie tells me that the non profit vitamin C foundation may be in for a small "windfall" of donations, and if we have enough to establish a laboratory, looking at GULO genetic engineering will be added to our list

Added

So if the GULO mutation hadn't "won out" then, we'd all make vitamin C, ergo any GPD Deficiency tendency would have died out.
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Re: Restoration of GULO functionality in humans?

Post Number:#4  Post by Johnwen » Mon Oct 15, 2018 3:56 pm

Here we go on this subject again and once again the subject of LP(a) is not being looked at, One item I will post shows that mice that normally produce their own V-C that are genetically altered not to produce it, start showing lesions forming rapidly when they start being deprived of an intake of V-C. They begin to develop lesions in their blood vessels caused by a break down of their cellular matrix.
The same fact that those life forms who do not produce their own V-C because of this so called Genetic Defect are producing LP(a) when those that do, don’t.
It’s also the reason Pauling and Rath targeted the LP(a) molecule in their studies and cures.

Lipoprotein(a) is primarily found in humans and sub-human primates and the emergence of the apo(a) gene was dated to about 40 million years ago, about the time of the divergence of the Old World and New World monkeys. This date coincides with the loss of endogenous ascorbate (vitamin C) synthesis, through a mutation of the gene for gulonolactone-oxidase (Gulo) in the ancestor of man. This fact led to the hypothesis that these two evolutionary events may have been connected. The loss of endogenous ascorbate synthesis rendered our ancestors susceptible to scurvy, a condition characterized by the impairment of collagen synthesis and ensuing loss of connective tissue integrity with hemorrhagic blood loss being the most frequent cause of death.


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4447075/

https://www.ncbi.nlm.nih.gov/pmc/articl ... 8-0325.pdf

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1853362/

So one can see there is a trade off From V-C to LP(a) Now the question is if one is successful in reactivating the V-C production what will happen to the production of LP(a). Will it disappear or will it return with a vengeance and claim it’s stake and go rouge and start doing damage??
I think one can see caution is the word when messing with Mother Nature!! :oops:
To steal ideas from one person is plagiarism. To steal from many is
research!

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Re: Restoration of GULO functionality in humans?

Post Number:#5  Post by whitenoise » Wed Oct 17, 2018 6:43 am

Some interesting replies, don't have the time at the moment to read these in depth, but hope the exchange of ideas and chat continues!

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Re: Restoration of GULO functionality in humans?

Post Number:#6  Post by ofonorow » Sun Oct 21, 2018 10:55 am

Johnwen is right!
I think one can see caution is the word when messing with Mother Nature!! :oops:


I don't know if the original post was a "set up" or just the universe talking... But it turns out (as I have just learned) that there is a group (or are groups) who believe the have a way to un-mutate GULO. They are EXCITED, because humans on their program are keeping vitamin C levels high, without supplementing vitamin C. I've been told that they even have avoided sickness/flu.

So before I share my response regarding their proposed mechanism, I am also excited that a major economic interest (e.g. the market is all human beings on earth) is aligning with what Pauling has said, and we have been saying since 1996. The right amount of vitamin C can make you live longer and feel better.

These group(s) recognized that to sell their product, humans must be made aware of our GULO genetic defect, which prevents us from making our own vitamin C, of experiments in vitamin C knockout mice which illustrate that giving back (supplementing) vitamin C increases the mouse lifespan by 3 times, etc. etc.

And to their credit, they know they will be attacked (given the economics of medicine - feeding on the sick) and part of the reason to contact our Foundation is to help get their ducks in a row.

Thomas Levy has been on the product, and he told me he thinks this may be the most important development in vitamin C in the past 20 years. Dr. Levy has allowed me to post and refer to a set of slides he now uses in his lectures. The last few slides are dedicated to overcoming the GULO defect, Find Endogenous Vitamin C Production with GULO near the end of https://vitamincfoundation.org//pdfs/LevySlides.pdf

The "Stop Codon" idea may be correct (They are promising to send me that papers on this) but per the following, I think other explanations are more likely. I have learned to keep an open mind. Here is a portion of my email to that group...



ofonorow wrote:Understanding why (and how) a gene is expressed in different types of cells is key to understanding if the GULO mutation can be overcome.

So my reservation about the validity of the STOP CODON is that there are about 33,000 STOP CODONS, and the ones we care about are located in liver (and possibly kidney) tissues.

What would happen if ascorbate could be made in EVERY cell? Who knows? GULO exists in the DNA of every cell, but is only expressed in certain tissues.

The other problem is the geneticists forum dedicated to GULO a few years back had the sequences of the nucleic acids in the GULO defect diagrammed, like a tree... The GULO mutation mutated over time! From the DNA mapping, of our, and primate, genomes, it was obvious there was a common ancestor, perhaps 3 million years ago (from memory Pauling guessed 3 to 30 million years ago based on the rate of mutations.)

It was easy to see that as the evolutionary tree split, there were small changes in GULO among the dependent species. The geneticists called GULO an "ancient" mutation. (And for any person doubting the theory of evolution, the changes in GULO over time/species discussion/diagram, was strong evidence. I may go looking for that forum again.)

The point is that the GULO gene evolved and exists in most animals over eons. If it mutated in most animals, that strain died out. In our case, it mutated, we survived, but the now-bad GULO gene and may have continued to mutate. Just overcoming a STOP codon doesn't guarantee we are returning to what nature intended.

If however, the technology you shared with me can target GULO, while exciting as heck, my thoughts immediately go to whether the technology can be applied to Telomerase!

Vision: vitamin C to have "healthy years" and telomerase to extend the life span.

Another theory is that the hard-to-pronounce 4th enzyme (you did a great job Bill) may be partially produced, such that adding a molecule or enzyme turns the partial 4th enzyme into the complete enzyme , right in the liver where it should be made. In theory, this would create an active enzyme (without really altering the GULO mutation). We have had forum posters citing literature (such as olive leaf or oil, cinnamon, etc.) that was supposed to do this.

You mentioned perhaps some DHA preservation as possibly creating the increased vitamin C level effect, but the body already does this - converts DHA back to AA, usually with glutathione and/or vitamin E, etc.

DHA has a very short half life in the blood before an enzyme (or the order of catalyse) deactivates it. The enzyme has a long name based on DHA.. and another explanation could be that what you are doing is inactivating that enzyme, leading to more DHA (which is vitamin C by the way). The problem with this, in theory, is more oxidative stress. More vitamin C in the blood/urine, but more stress. (And according to chemist Boyd Haley, there is a test for oxidative stress, based on the glutathione content inside cells. This blood assay should be part of the clinical experiments).
Owen R. Fonorow, Orthopath® (Orthomolecular Naturopath)
® is a trademark of the Institute for Orthomolecular Studies

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Re: Restoration of GULO functionality in humans?

Post Number:#7  Post by whitenoise » Thu Oct 25, 2018 10:28 am

This is very interesting information indeed Owen, thanks for posting this in this thread. Like you said, obviously karma that I started this post :) I've just opened up your pdf and its very interesting. I'm currently reading the pubmed study that is mentioned on the last couple of slides.

My only concern is the economic aspect you mention. Obviously this is a big thing, and if where possible to correct this mutation then I'm sure people (who are aware of the problem) would be willling to pay lots of money to correct this. However, is this the correct approach? In a sense the rich get richer, and the poor get poorer, to coin a phrase. However something like this requires research, development, peoples time, materials and lab space, so there would be a cost in this. So I glad that they have contacted the Foundation to get advice here.

Surprising to hear about Thomas Levy on the 'product', he's been keeping that quiet ;) But I agree this could be potientally a very exciting time!

You mention about Telomerase, I know a little about this, and the possiblity of doing what you said is wow. However in order to get my knowledge more up-to-speed, do you recommend any good books/reading on this subject?

Regarding the group(s) that are talking about this, is it possible to join this as I would very interested to keep abreast of their current developments.

Finally. thanks for the info, and I look forward to more updates!

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Re: Restoration of GULO functionality in humans?

Post Number:#8  Post by ofonorow » Thu Oct 25, 2018 2:51 pm

You mention about Telomerase, I know a little about this, and the possibility of doing what you said is wow. However in order to get my knowledge more up-to-speed, do you recommend any good books/reading on this subject?


Telemore TImebombs by Park is an excellent way to come up to speed. Amazon or we have it https://inteligentvitaminc.com/cart/index.php?main_page=product_info&cPath=4&products_id=66



Regarding the group(s) that are talking about this, is it possible to join this as I would very interested to keep abreast of their current developments.



I am speaking with people who I believe are in league with Dr. Levy, and they mention "other groups" moving on the basis of the same research, perhaps in another direction. The people I spoke with promised me the basic research papers (not clear if published) and I am still waiting.
Owen R. Fonorow, Orthopath® (Orthomolecular Naturopath)
® is a trademark of the Institute for Orthomolecular Studies

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Re: Restoration of GULO functionality in humans?

Post Number:#9  Post by whitenoise » Sat Oct 27, 2018 5:57 am

I have downloaded the book your recommended Owen and will add it to my reading list, thanks.

If you could me, and others, updated on this topic that would be great as I'm interesting in these current developments.

Also, I shall certainly look more into Hydroxytyrosol as mentioned by the PubMed study.

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Re: Restoration of GULO functionality in humans?

Post Number:#10  Post by whitenoise » Sun Nov 11, 2018 11:25 am

Any news/updates on this topic Owen?

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Re: Restoration of GULO functionality in humans?

Post Number:#11  Post by pamojja » Sun Nov 11, 2018 3:27 pm

Wow. So interesting. Therefore it's actually not Olive leaf or fruit, but concentrated hydroxytyrosol at 45 mg for 8 weeks that doubled vitamin C serum levels. The best about that is, that's an amount that can even be get from diet, since raw black olives contain in average 65.93 mg/100 g!

However, wikipedia gives the caution to check the ingredient label of any salted olives:

However, it was found that black olives, such as common canned variety, containing iron(II) gluconate contained little hydroxytyrosol, as iron salts are catalysts for its oxidation.[2]

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Re: Restoration of GULO functionality in humans?

Post Number:#12  Post by johnyascorbate » Mon Nov 12, 2018 3:33 pm

This is very exciting stuff. What does everyone think about the possibility of making the body produce its own Vitamin C. How much will the body be able to produce? Is it cheaper than just buying ascorbic acid?

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Re: Restoration of GULO functionality in humans?

Post Number:#13  Post by confused1 » Tue Nov 13, 2018 7:44 am

However, it was found that black olives, such as common canned variety, containing iron(II) gluconate contained little hydroxytyrosol, as iron salts are catalysts for its oxidation.[2]

The iron gluconate is added to give the olives a uniform black color. Green olives provide a similar amount of hydroxytyrosol with no iron gluconate.

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Re: Restoration of GULO functionality in humans?

Post Number:#14  Post by pamojja » Tue Nov 13, 2018 8:22 am

johnyascorbate wrote:This is very exciting stuff. What does everyone think about the possibility of making the body produce its own Vitamin C. How much will the body be able to produce? Is it cheaper than just buying ascorbic acid?


Am less excited after asking myself the same questions and reading the actual study:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5219601/

These results indicate a physiologically relevant antioxidant function for dietary HT due to its vitamin C saving effect.


They didn't even think about Gulu functionality as a possible explanation, much less testing for it! Therefore those ideas of Dr. Levy - with all my respect - are nothing more than wild speculations. Just think about how much, just as an example, quitting to smoke could raise vitamin C in serum due to it's vitamin C sparing effect? That also nobody would take to mean the Gulu defect has significantly improved.

The subjects showed low levels of vitamin C at baseline (ranging from 8.4 to 48.6 µmol/L). Intake of the HT supplement increased the serum concentration of vitamin C by 2-fold at T4 (P<0.001), and the levels were sustained for the following 4 weeks (T8).


In average HT raised serum vitamin C from an average of 23.4 to 46.4 after 4 weeks, and not increasing much further than 47.8 micromol/l after 8 weeks. And do take a look at this actual graph: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5219601/figure/f0005/ Most participants of this study had been terribly deficient, except in 2 subject. And as far as discernible from that graph, in exactly those 2 somewhat sufficient subjects serum levels didn't increase any!

So my meanwhile conclusion from this study is, there seems to be indeed a vitamin C sparing effect with 45 mg/d of hydrotyrosol, but only in the highly deficient. With really no indication till now, that it would restore Gulu functionality at such a dose, beside an obvious vitamin C sparing effect.

Consider that according to an other New Zealand study vitamin C mega-dosers (~ 20 g/d) consistently show serum levels even above 400 micromol/L! I very strongly doubt due to everything said that such high levels could ever reached with hydrotyrosol, even when supplementing in Grams per day.

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Re: Restoration of GULO functionality in humans?

Post Number:#15  Post by johnyascorbate » Wed Nov 14, 2018 1:35 pm

You make some very good points, pamojja.


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