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basmwklz OP t1_j95qa3x wrote

Abstract: >Pharmacological vitamin C (VC) is a potential natural compound for cancer treatment. However, the mechanism underlying its antitumor effects remains unclear. In this study, we found that pharmacological VC significantly inhibits the mTOR (including mTORC1 and mTORC2) pathway activation and promotes GSK3-FBXW7-mediated Rictor ubiquitination and degradation by increasing the cellular ROS. Moreover, we identified that HMOX1 is a checkpoint for pharmacological-VC-mediated mTOR inactivation, and the deletion of FBXW7 or HMOX1 suppresses the regulation of pharmacological VC on mTOR activation, cell size, cell viability, and autophagy. More importantly, it was observed that the inhibition of mTOR by pharmacological VC supplementation in vivo produces positive therapeutic responses in tumor growth, while HMOX1 deficiency rescues the inhibitory effect of pharmacological VC on tumor growth. These results demonstrate that VC influences cellular activities and tumor growth by inhibiting the mTOR pathway through Rictor and HMOX1, which may have therapeutic potential for cancer treatment.

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AllanfromWales1 t1_j95r1p4 wrote

And non-pharmacological Vitamin C? Should I just stop eating fruit and veg and just take supplements instead?

−7

crazyhadron t1_j95rozz wrote

Replying to AllanfromWales1 (#1,869,527)

>Pharmacological vitamin C (VC) is a potential natural compound for cancer treatment.

Pretty sure they are the same thing (abscorbic acid). Chemistry's chemistry, whether it be from a fruit or from someone's lab

−1

Knute5 t1_j95sf8g wrote

Norman Cousins was saying as much decades ago.

14

RepresentativeFox149 t1_j95sgix wrote

Replying to AllanfromWales1 (#1,869,527)

Emphasis added.

“The intracellular VC concentration is strictly regulated in order to maintain levels of 80–100 μM in the plasma [2, 3]. However, intravenous injection bypasses this strict regulation, allowing specific VC concentrations to be maintained within a specified period, thereby providing a pharmacological basis for its therapeutic application [4]. Several pioneering studies have demonstrated the efficacy of pharmacological VC in improving the survival of patients with advanced cancers [5, 6]. In contrast, two randomized double-blind controlled trials failed to demonstrate any benefit of VC against advanced malignant disease [7, 8]. Therefore, the route of administration is important for high-dose VC to have a therapeutic effect, and only intravenous administration results in sufficiently high plasma and urine concentrations to allow potential antitumor activity [9].”

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Niceotropic t1_j95t7vb wrote

To be clear, you're not missing anything, there is no difference between "pharmacological vitamin C" and vitamin C. They are both ascorbic acid.

The motivations for using this obfuscating term are unsupported in the text and make no sense.

70

laserinlove t1_j95u29x wrote

Replying to AllanfromWales1 (#1,869,527)

The authors are using the term pharmacological to refer to plasma concentrations that are only achievable by IV administration.

Per the authors, the body regulates Vitamin C to 80-100uM so you can't just consume more of it. IV administration however gets around the natural intestinal absorption limits.

So unless you plan to shoot up your supplements, this doesn't seem applicable to typical person just yet. Though I must say I'm imagining a funny skit where we see what appears to be a drug den of people shooting up and it's a bunch of natural herbalist types cooking up and injecting vitamin c from a pile of oranges.

28

RepresentativeFox149 t1_j95ukh9 wrote

Replying to Niceotropic (#1,869,728)

Emphasis added.

“The intracellular VC concentration is strictly regulated in order to maintain levels of 80–100 μM in the plasma [2, 3]. However, intravenous injection bypasses this strict regulation, allowing specific VC concentrations to be maintained within a specified period, thereby providing a pharmacological basis for its therapeutic application [4]. Several pioneering studies have demonstrated the efficacy of pharmacological VC in improving the survival of patients with advanced cancers [5, 6]. In contrast, two randomized double-blind controlled trials failed to demonstrate any benefit of VC against advanced malignant disease [7, 8]. Therefore, the route of administration is important for high-dose VC to have a therapeutic effect, and only intravenous administration results in sufficiently high plasma and urine concentrations to allow potential antitumor activity [9].”

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TheCrimsonSteel t1_j95utvd wrote

Replying to Still-WFPB (#1,869,612)

Looks like the other big thing was giving it by IV so they could get to concentrations that would normally capped by the body's regulation mechanisms?

2 or 3 comments up another Redditor breaks down the difference

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johanvondoogiedorf t1_j95wucj wrote

What the hell is pharmacological vitamin c and does it know normal vitamin c

245

shiny_brine t1_j967hy2 wrote

Replying to AllanfromWales1 (#1,870,053)

To simplify a very complex system, there are four main uptake paths for VC (passive diffusion, facilitated diffusion, active transport and recycling through the kidneys). Difference subsystems (brain, lungs, heart, muscles etc.) can each tolerate different levels of vitamin C and regulate levels through the use of different uptake paths. These levels are lower than the levels discussed in the paper obtained through intravenous means. If the body were exposed to long term high levels as discussed in the paper, there would be concerns of damage to many of the systems that need to regulate much lower levels. If one where to ingest large doses it would mostly go through the recycle system and be removed by the kidneys before it would get to the sub-systems.

3

thirdtimenow t1_j96afwf wrote

Interesting this goes some to explaining why people heal from cancer doing IV drips.

−3

asapfroggx t1_j96dz6u wrote

so Linus Pauling was at least partially correct…

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xlews_ther1nx t1_j96gj9h wrote

I'm pretty sure I saw a doc on this like 15 years ago on Netflix.

3

Innundator t1_j96ievd wrote

Replying to Niceotropic (#1,870,184)

Your argument is that there should be no differentiation between a rock containing iron, and an actual hammer composed entirely of iron. Because it'd be confusing to call them both anything but iron.

The difference between a pharmacological dose and what's found in an orange is many orders of magnitude, which warrants a new term.

7

pdxmhrn t1_j96k67v wrote

I know some of these words

5

Time8u t1_j96r9dw wrote

Replying to Innundator (#1,871,963)

No new term is needed. It should be called "intravenous" vitamin C. Calling it "pharmacological" is a way of making something that is concrete and simple abstract instead and whoever came up with it is intentionally trying to make this appear more sophisticated than it actually is.

17

Kailaylia t1_j96rxtv wrote

Replying to Niceotropic (#1,869,728)

>They are both ascorbic acid.

Most likely, in this case.

However, there are many forms of "pharmacological vitamin C". For example, calcium ascorbate, ascorbates of various other minerals, liposomal vitamin C and ascorbyl palmitate.

1

CrateDane t1_j96s3pv wrote

Replying to KetosisMD (#1,869,605)

Well, Rapamycin mainly inhibits mTORC1, while this seems to target RICTOR for degradation and thus preventing assembly of mTORC2. So they would have complementary roles if you wanted inhibition of both complexes.

7

Kailaylia t1_j96txc2 wrote

Replying to Amesenator (#1,871,668)

>Liposomal-encapsulated Ascorbic Acid: Influence on Vitamin C Bioavailability and Capacity to Protect Against Ischemia–Reperfusion Injury
>
>The data indicate that oral delivery of 4 g of vitamin C encapsulated in liposomes produces circulating concentrations of vitamin C that are greater than unencapsulated oral but less than intravenous administration

8

guystarthreepwood t1_j96tye4 wrote

Replying to Appropriate_Banana (#1,871,255)

Preface: it has been a minute since I studied these systems in detail, this is the jist of it. Vitamine c is a redox active molecule existing in an equilibrium between reduced and oxidized forms tending to favor the reduced form. Ascorbic acid (reduced vitamin c) gets oxidized by taking on a single electron from a radical (molecule with an unpaired electron) to form oxidized vitamin c. If it is exposed to oxygen or other oxidants for long periods of time it will exist largely in the oxidized form and end up being a prooxidant rather than antioxidant in order to re-establish the equilibrium. Your body is able to reduce oxidized vitamin c via various intracellular antioxidants (glutathione etc) but that initial exposure will produce some ROS.
Also in cell culture, there's often a high concentration of free iron floating around (5mM) which is totally unnatural. The free iron/vitamin c combo is able to create a Fenton reaction and produce huge amounts of ROS.

8

Innundator t1_j96y7ye wrote

Replying to Time8u (#1,872,733)

You should tell the people doing the research! You're obviously more aware of how things work than they are, and that they haven't heard from you yet is really a travesty of science.

Why are you hiding your brilliance from the world

−9

Pretty-Theory-5738 t1_j973pod wrote

Replying to Niceotropic (#1,870,184)

Technically you could also deliver a low dose intravenously as well, so that’s not really a complete descriptor either. A more clear descriptor for a lay audience might be “high dose intravenous”.

But this actually still misses a small nuance, which can be understood once we know the context of how scientists tend to use the jargon of “pharmacological dose”. In bio research, we use this term mainly in contrast with “biological dose”. A biological dose refers to something relatively within the range of what could occur naturally within the body, through food consumption and/or the body’s creation of that chemical, depending on which chemical we’re talking about.

A ‘pharmacological dose’ is something significantly higher than what would occur naturally in the body. In this case with vitamin C, it’s more possible to achieve a “pharmacological dose” through IV (although with many other chemicals you can achieve a “pharmacological” dose orally if there’s not much restriction on absorption). Anyways, the point is that even saying “high dose” is not fully informative, because the scientist could be referring to just a high ‘biological dose’. Saying pharmaceutical dose gives a nod to the relative scale of the dose that we’re talking about.

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Jaredlong t1_j9765gr wrote

Let's revise the adage to "An orange a day, keeps the doctor away."

1

Still_Maverick_Titan t1_j97sxdj wrote

I have no idea what any of this means but it sounds awesome and gives me hope for the future.

1

basementreality t1_j97vgw8 wrote

Replying to [deleted] (#1,872,737)

IRC Rapamycin is a drug given to organ transplant recipients that is also used by people trying to extend lifespan. It has been shown in studies to extend the lifespan of pretty much every organism it has been tested on.

It's mechanism of action is too complicated for me to recal but there are lots of explanations online.

It's a super interesting molecule that has a very interesting history as it was discovered next to a statue on Easter Island.

11

Xw5838 t1_j981yy0 wrote

Replying to someone_actually_ (#1,874,449)

Just like William Colby with bacterial immunotherapy before it even had a name. Ignored then vindicated.

And back in the 70's Pauling found that intravenous Vitamin C significantly extended the lifespans of cancer patients in studies.

The Mayo Clinic in a fake attempt to "replicate" the findings only used the pill version of Vitamin C in their own study to the tune of around 10 grams. The results were negative and they crowed that Vitamin C doesn't work. And that was that.

Other researchers though who properly replicated the findings got positive results.

Now the science behind it is that Vitamin C produces Hydrogen Peroxide in cancer cells which basically shreds them via oxidation because they don't have as much catalase in them like normal cells which neutralizes the H202.

As for why doctors don't prescribe it to all cancer patients. It's obvious. Vitamin C can't be patented. So there's no money in it.

7

wickzer t1_j98a3k7 wrote

Or is this lack of vitamin c induces mTOR... Etc? Which makes sense, nutrient depletion is bad... But less impressive of a finding.

0

Darkhorseman81 t1_j98ihjn wrote

Vitamin C regulates TET2, a gene that regulates epigenetic quality control in the blood.

It is so efficient, if you get a loss of function mutation of TET2, Vitamin C can replace its function, weirdly enough.

I'm on my phone so it's a hassle to link studies, but type Leukemia tet Vitamin C into a search engine. Some pop up pretty easily.

Vitamin C alone can treat some forms of Leukemia.

Some, not all. Don't expect it to be a miracle cure or anything.

It's weird, but ancient humans had the ability to produce Vitamin C from Glucose. Over time, through mutations and silenced genes, we became Vitamin C auxotrophs, requiring it from the diet.

The way we evolved our bodies do not stock pile it like oil and fat soluble vitamins, because we used to make what we needed on demand; there was no need.

Now, we use what we need in the moment and excrete the rest.

The loss of this Vitamin C producing capability lead to epigenetic instability. Means we can mutate and evolve faster, but also means we are more prone to cancer and dysfunction.

I've added a 24 hour slow release Vitamin C in its native form to a muscle wastage and anti aging protein powder I'm working on.

1

Darkhorseman81 t1_j98ivtb wrote

Replying to [deleted] (#1,872,678)

Mega dose is stupid. The body uses what it needs in the moment and excretes the rest.

Slow release Vitamin C, 24 hour slow release, is what you need.

Ancient humans had genes to produce their own constant low supply Vitamin C. These genes were lost or silenced.

This has lead to loss of epigenetic quality control, particularly in blood. As Vitamin C regulates a quality control gene called TET2, which is related to DNMT DNA methyltransferases.

Means we can mutate more and evolve quicker, but makes us more predisposed to cancer, oxidative damage, and dysfunction.

When we were monkeys eating lots of fruit, almost constantly, I guess our body thought it was a good trade-off.

Now with drought flood drought flood levels of Vitamin C in the modern diet, it's lead to epigenetic chaos.

Deficiency in Queuine, unpredictable Vitamin C and Folate levels leads to aberrant oxidation states in Tetrahydrobiopterin, for starters.

Loss of Mitohormensis, as one of a million things this leads to.

20

NutrientBrief t1_j98l9og wrote

Interesting, always glad to see more research on vitamin C in preventing and treating cancer!

−1

discretion t1_j98x25t wrote

Replying to Xw5838 (#1,876,402)

This can't be true, can it? Oncologists everywhere are so beholden to pharmaceutical companies that they won't prescribe vitamin C intravenously? This sounds like a thing I would've heard of by now, a vast global conspiracy to deny cancer patients across the globe a simple and cheap cure.

11

fullmetalmuumuu t1_j997k68 wrote

More evidence supporting Linus Paulings claims about vitamin C and cancer. I wonder if the medical industry will continue to lie about vitamin C, like they did when Pauling first made claims about it?

0

Daaru_ t1_j99rwsw wrote

Replying to discretion (#1,879,421)

It's like the plot of Dallas Buyers' Club, if any research suggests that something expensive is better then it will be used regardless of how efficacious it is. It's not black and white like a conspiracy and instead varying shades of grey. Vitamin C gave mixed results without toxicity instead of chemotherapy drugs giving mostly positive results with toxicity being a common side effect, so the latter is more medically sound for treating the issue for doctors. You learn pretty quickly that many doctors accept harmful side effects if the issue is treated at the expense of the patients.

1

ManWithTheAd t1_j99ymy2 wrote

Meachanistic studies aren‘t worth much. Better to have studies in living humans and measure hard endpoints like cancer incidence and mortality.

2

erebos290696 t1_j9a0js8 wrote

I swear if Linus Pauling or whichever Nobel prize winner it was turns out to be right on this.

−1

erebos290696 t1_j9a0txa wrote

Replying to fanghornegghorn (#1,874,990)

It has several functions which include immunosuppression and fungicide.

The immunosuppressive effects allowed it to be used in organ transplants I believe. And the low rate of cancer in patients using it, lead to the discovery of the mTOR pathway. And it's use in cancer treatment.

I think. Verify everything I've said as it's been a minute since I learned this.

0

SaltZookeepergame691 t1_j9a94us wrote

Replying to discretion (#1,879,421)

No, it is not true. There are some elements of truth (eg, the patentability of vitamin C [and any unpatentable agent] does hinder research, but that ignores that a lot of research is done/funded by not-for-profit/governmental agencies around the world), but it is not a 'global conspiracy' to suppress a miracle cure.

I think it's also worth pointing out that enthusiasm in medicine in general is pretty tempered because with vitamin C we've been here quite a lot before. Eg, IV doses were heavily promoted by some fringe medics as being a revolutionary cure (ie, reducing death by nearly 90%) in sepsis ICU patients, but we now know that risk of death is at the very least not decreased and in is often increased by high doses. I think IV vitamin C is a difficult sell to funders, when there are many such potential avenues to investigate. There is some promising preclinical evidence, eg in this study, and it may be that there will be a new wave of trials as that evidence accumulates to convince people.

7

rdizzy1223 t1_j9am8x9 wrote

Replying to cjankowski (#1,871,222)

That isn't all it means, it means it needs to be administered via IV, it will not reach blood serum levels high enough if you take it orally, regardless of how much you take, you are just wasting it.

2

cjankowski t1_j9atjki wrote

Replying to rdizzy1223 (#1,884,516)

That isn’t inherent to the term (which also applies to cell culture studies) - pharmacologic ascorbate typically just means > 1 mM, which yes is only possible in human serum via IV

2

vipw t1_j9ecjbh wrote

Replying to rdizzy1223 (#1,884,555)

In a palliative setting, it makes a lot of sense to use treatments with fewer side effects even if the effectiveness is worse.

The cytotoxic chemotherapy drugs have truly horrible side effects.

1