Vitamin C and Immuno-Oncology
blogs.sciencemag.org
blogs.sciencemag.org
High-dose vitamin C enhances cancer immunotherapy https://stm.sciencemag.org/content/12/532/eaay8707/
Takeaways:
Oral Vitamin C and intravenous Vitamin C have vastly different pharmacokinetics and effects on cancer.
- Low dose vitamin C (oral) is anti-oxidant and may attenuate chemotherapy:
Chemosensitizing effect of vitamin C in combination with 5-fluorouracil in vitro https://www.ncbi.nlm.nih.gov/pubmed/12929582 "only a high concentration of vitamin C increased the cytotoxicity of 5-FU"
Ascorbic acid attenuates antineoplastic drug 5-fluorouracil induced gastrointestinal toxicity in rats by modulating the expression of inflammatory mediators https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5598240/
- High dose vitamin C (intravenous) is pro-oxidant
- High dose vitamin C (intravenous) alone slows tumor growth
- High dose vitamin C (intravenous) combined with immunotherapy has a synergistic effect
High dose vitamin C (intravenous) also synergizes with chemotherapy and spares healthy cells https://stm.sciencemag.org/content/6/222/222ra18
If you are in chemotherapy or immunotherapy, stay away from low doses of oral anti-oxidant supplements such as Vitamin C.
You can see all the oral studies here: https://shorturl.at/mvxy4
You can see all the IV studies here: https://shorturl.at/bn019
The results of the research will be published soon...
You can see all the oral studies here: https://bit.ly/3ct2q4u
You can see all the IV studies here: https://bit.ly/2Th9ud5
Vitamin C pharmacokinetics: implications for oral and intravenous use https://www.ncbi.nlm.nih.gov/pubmed/15068981?dopt=Abstract
- single study
- on mice
- hasn't been replicated
- purely speculative mechanism of action (How exactly is Vitamin C helping? They don't know!)
I have a different perspective, however. As someone who is expected to die of cancer within a few years, even early/flawed research is of interest. Especially with the cognitive impairments I feel from chemotherapy, I find it challenging to wade through all of the ideas and opinions to get to information that's useful in guiding decisions about my treatment.
In particular, this thread acquainted me with jcims's life experiences. I take his statements at face value and believe that he's indeed spent countless hours researching various treatment possibilities. That he is left with the belief that vitamin C has promise as a treatment option gives me cause to further explore the relevant science. I lack the time, energy, and knowledge to investigate the plethora of options/speculation, so I greatly appreciate when another credible person points me in a direction that's worthy of greater attention.
This doesn't mean I'm planning to ask my oncologist about vitamin C or pursue this as a treatment option at this time. :) It just gives me a promising area of further exploration and I'll see where it leads me.
From this thread, I also gained reinforcement (in part through pazimzadeh's summary, below) of my understanding that taking vitamin C oral supplements during chemotherapy is ill-advised. I'd come across this guidance before, but have been reminded of it by this article and this discussion.
So, my request to you is to please not discourage posts such as this article here on Hacker News. If you prefer to not have your "time wasted [by] this stuff" then please don't click on such articles or please suffer in silence. Or, better yet, post your summary of the research's limitations, as you've done here. (That is, your summary is useful, but your first line saddened me, as I appreciated having my time "wasted" by this article and the subsequent discussion. I hope others here do not heed your request.)
Edit: minor editing to simplify. (I realize this post is still rather wordy, please forgive.)
It took me a little while to sort it out, but I've come to the conclusion that these (mostly young) doctors are so incredibly leveraged in their position by student loans and sunk cost into their education that they simply cannot risk anything outside of the prescribed approach to care for a patient...particularly one where there is generally a foregone conclusion as to the outcome. I initially raged against them individually, but now I see them as scared children and my hatred is directed towards the system that creates this fear. Should I encounter this situation again, my first goal will be to find a doctor with a terminal illness themselves and see if we can't forge a new path together.
None of the 'standard of care' therapies for, in our case, ovarian cancer are guaranteed to be effective...they simply have hazard ratios that are more favorable than the rest. So, quite literally, doctors are already guessing as to what to do next once you are in a recurrent cancer setting (even before, really).
On top of that there is a mountain of clinical evidence that high dose intravenous vitamin C (IVC) has an incredibly low risk of adverse events in healthy patients and there have been clinical trials and case studies indicating that it improves quality of life in cancer patients undergoing chemotherapy. Evidence that IVC actually has a therapeutic benefit in killing cancer is starting to emerge, but definitely needs work to meet the standard of testing that is generally mandated for something to become standard of care.
So now we're in this weird local minima of scientific interest in a potential therapy. Nobody that I've seen is seriously suggesting that IVC is an effective monotherapy against any kind of cancer. But there is growing evidence that it is a safe and effective adjunct therapy to increase quality of life and potential outcomes for many patients. Unfortunately, clinical trials are expensive and most oncology teams are not interested in results that haven't specifically tested the cancer that they specialize in. So you are left with waiting for someone to explore the enormous graph of specific cancer treatment settings and apply this trial. In other words, it's not coming to a theater near you any time soon.
Meanwhile people are dying because the current treatments are not working, and finding a doctor with the guts to explore these options with a willing and educated patient is, in my personal experience, next to impossible.
This quite reasonably makes most doctors very cautious during the process. To the point where significant studies on exercise have been done to verify it’s still safe.
An extreme example would be if a suicidal patient asked their therapist to put a bullet in their head rather than give them an antidepressant, should the patient be free to ask for this and should the therapist be obligated to fulfill this request? It's a question of what is ethical and that goes beyond your own agency. You are free to put a bullet in your own head, or find your own source of vitamin C, but you can't put that ethical dilemma on the doctor and expect a result.
Cancer may feel like a sentient adversary at times, but it’s just genetic instability (volatility?) combined with suppressed apoptosis, self-sustaining growth/replication signaling, immune evasion and angiogenesis to sustain large populations.
This results in an evolutionarily supercharged population of non-functional cells that out-compete normal cells until a major system is disrupted. The nature of a specific cancer cell is going to be informed by the primary source, so while they frequently share characteristics they aren’t the same and don’t generally respond to the same treatments. Saying that eating fruit and elevating blood pH is going to make them all go away is pretty absurd...it didn’t work out for Steve Jobs. Even if the pH thing was generally true, the tumor microenvironment would quickly adapt to foster a locally acidic pH.
IMHO an assisted human immune system will be the ultimate answer to cancer.
I do agree that biopsies of encapsulated tumors are a terrible idea. But once the cat is out of the proverbial bag in stage III/IV think they are useful.
I have been involved in natural healing for over 30 years. I have seen countless people cure cancer. I know this is not something HN crowd welcomes, and that is unfortunate. Cancer has been solved a long long time ago. Grape fasting, aronia fasting, combined with periods of dry fasting + specific herbs + kidney glandulars can heal pretty much every disease known to man. Cancer included.
Chemo is barbaric, but it has kept people alive.
If they have data on different therapies, they are not guessing. The data might not be perfect, but it's all we have, so it guides clinical decisions.
On top of that there is a mountain of clinical evidence that high dose intravenous vitamin C (IVC) has an incredibly low risk of adverse events in healthy patients and there have been clinical trials and case studies indicating that it improves quality of life in cancer patients undergoing chemotherapy.
I think we have different definitions of "mountain of clinical evidence". There is more data to back up the standard of care than the use of vitamin C.
I'm sorry but there are cases where they are definitely guessing and will sometimes admit as much. It's an educated guess but if you ask a doc to, for example, strongly justify why they selected one of the three approved PARP inhibitors for an ovarian cancer therapy, you're going to see a little of that uncertainty in living color.
The burden is on the patient to be their own advocate and parse through the various opinions (and their own research) to decide on the best treatment choices, with the assistance and guidance of the experts. Because despite them being experts, they have insufficient time to research and understand all of factors that are applicable to an individual's situation. (For example, in at least one matter, I proposed a significant change to the treatment plan and my oncologist agreed with the underlying logic and we made the change. Had I not mentioned it, it wouldn't have happened.)
It seems like there are a few bounds within which a doctor, and the healthcare system (including insurance companies), are prepared/allowed to vary treatment. I imagine some patients, especially those with potentially terminal conditions, are interested in treatment options that fall outside of those bounds.
(Perhaps if one's cancer follows one of the most normal/common paths, then blindly following standard of care is sufficiently wise. I'm not sure how often this is the case, but my impression is that there is great variation even within cancers of the same general type.)
To be sure, it would take a non-trivial time investment on their part. However, many doctors (though not all) seem entirely blind to anything they are not familiar with already, even if there would be reasonable scientific basis. There can be a level of pride there.
Thus, MDs are disincentivized from being creative or innovative outside of pure research settings.
Except "everyone else does it this way" is quite literally an acceptable definition of "reasonable"...
We've definitely lost the cowboy culture that basically cured leukemia. I don't know if that is a good thing or not. Trump's new FDA law allows for some more experimentation but it's not clear it'll work.
Hopefully, the new FDA personalized precision medicine approach will allow for individual treatment that can still be aggregated into clinical trials. I think there are a lot of re-purposing experiments going on with AI/big data that should translate into preclinical work and possible new clinical trials.
Also as I mentioned above, there are very few trials for 'cancer', they are almost all disease-specific because the oncologists want to know how it's going to affect their specific situation. This multiplies the surface area that needs covered in a trial, increasing the cost (and delay).
Allowing patients, particularly terminal ones, to make informed decisions on treatment that hasn't been approved is morally correct in my opinion and definitely a way forward. Ideally each little 'experiment' would be tracked in some way to start creating enough of a sample size to draw some statistical conclusions. This could then drive interest in running a full set of trials on the therapy.
Then at his normal oncologist, a brand-new drug was recommended that only worked on cancers caused by NTRK gene fusion - but my dad would have had to get a third biopsy to confirm that and get the prescription. Why didn't they get enough material the first or second time? Nobody could say. Every step of the treatment process was done piecemeal and ultimately my dad was in no condition to get yet another biopsy. I wish there was some process by which he could've just gotten the damn pills in the off chance there was a response.
>I don't know if there was anything else I could have done
This is a terrible feeling, I know it well.
This all makes sense if you're looking at trials as a way to determine if a therapy works. If you're looking at them as a way to access experimental medicine, however, it is pretty disappointing.
In other words, I suspect the emotions you're detecting are probably exhaustion and annoyance, and any genuine fear is most likely going to be that they fear for your outcome should you deviate from what they believe to be the best course of action.
I can assure you that my wife and I received orders of magnitude more nonsense from friends, family, colleagues and random assholes in the mall that saw her headscarf. The amount of unsolicited packages and potions we received at our doorstep from anonymous people over the course of her treatment puts anything that I brought to her doctor to shame.
>I'm sure in the modern era, when they are just trying what they know is the best researched, best chance they know for a successful path for you or your loved ones, they are beyond sick of hearing your alternative theses assembled from mommy blogs and witch doctors.
I get it. I really do as I personally was asked repeatedly to 'just try this' random bullshit for my wife all the time. There's a huge gap between sprinkling lion's mane mushroom on your eggs and seeking treatment for my wife's hyperglycemia that put her solidly in the diabetic category. Endocrinology wouldn't treat it because she didn't show elevated A1C, but I had nobody in my wife's corner to explain why A1C isn't a good signal when you're severely anemic and getting transfusions every other week. Google 'hyperglycemia cancer progression' with a 'site:gov' to keep it from NIH and other government agencies. There's a GIANT FUCKING SIGNAL that elevated blood glucose increases cancer progression, but I couldn't find a single doctor to even listen. To them it's all equivalent bullshit.
Maybe it's not fear then. Maybe it's apathy. I'm not sure that's better.
Today everyone, even doctors, knows that high blood sugar levels increase the odds of cancer AND diabetes. That's why everyone and his dog is taking metformin and why that drug is almost always the first ingredient included in "life extension" cocktail drug tests.
But: High glucose levels do not cause diabetes. Diabetes causes high glucose levels. Once they go up you need treatment as you either have no insulin or are producing not enough and need to mediate that. Both are diabetes.
Ding ding ding. My wife's blood glucose levels went from normal 90's range to averaging around 120 over the summer to averaging close to 200 last December. Her liver had a heavy disease burden, and my understanding based on my own research (because none of her doctors would address it) is that this can affect insulin sensitivity, which in turn can cause elevated blood sugar. This does not seem to be a dominant effect, however, and can go the other way as well.
When it does create hyperglycemia though, it also creates an unfortunate feedback loop in that the elevated blood sugar levels can increase the cancer progression, compounding the effect.
But guess what, nobody will bite. I had to go to some weird third party service to get a prescription and spend weeks going back and forth with oncology and endocrinology to get anyone to comment on it. Oncology said NFW with zero rationale and endo said a small starter dose with regular monitoring for lactic acidosis due to compromised liver function.
https://www.nature.com/articles/s41467-018-07857-9
Reducing blood glucose and A1c levels may be a good idea for other reasons, but it won't cure cancer.
I make no judgement on the validity of your request. From my point of view, people have been banging on about IV vitamin C therapy in cancer for years but never actually done a properly powered double blind randomised placebo controlled trial to show that it works. We can complain about lack of funding, obstructive medical systems etc, but if some people really think IV vitamin C is the best thing since sliced bread then they would find a way to get the trial done.
I'm pretty confident IVC will end up at least as part of palliative care. Nobody is going to fund trials for it for adjunct cancer therapy because onc docs want to see trials for their specific cancer and given it's not even a candidate for monotherapy it's just not going to get the investment.
Self-serving because, naturally, the reason that your requests are met with poor regard isn't because there's something wrong with the request, but because something is wrong with the person receiving it. But that's okay; that's the nature of human opinion and subjectivity. You can accuse me of the same, of course - oh, and will. I'm sure this thread will go from Zero to Malpractice in 6.4 seconds.
But wrong:
You're going to ignore this sentence, but dear god, do I want to burn it into your eyeballs, and the eyeballs of every person reading this: I care. The vast majority of my colleagues care. The vast majority of nurses care. The vast majority of everyone you meet in the hospital cares. They've been there, either themselves, or with a loved one; have been there in the past, or are there now, whether or not they disclose that to you. They give a shit.
When we work with someone that is suffering and dying, we care. We hurt. And when, god help us, there's a chance we can actually help and reduce that suffering, be it for the patient or their family, and they take that away from us, we hate them a little. We hate them for making us care, and making us watch and experience and share this suffering when maybe we didn't have to.
When a patient says, "You know, it's really important to us that we explore (dubious option X)", it puts up our radar for "oh fuck, this is going to suck." And the more the patient goes down that road, the more we know they're going to veer away from care that's at least have some evidentiary basis to support it working, the more we know we have to go down the fucking drain with them.
Not that long ago we had a lady on our IM service who'd had a promptly diagnosed, treatable, resectable local cancer... 18 months ago. 18 months of quack bullshit later, she came in to us because of the severity of her constipation, because that cancer arose near her intestines, and had now matted and infiltrated them. She and her family were proof to all conversations regarding reality: she just needed IV nutrition of the appropriate sort, because the problem wasn't that the cancer had utterly invaded her GI tract, it was that she needed the right vitamins! Our nutritionist couldn't come up with the miracle combination of IV nutrition for her, because she kept deteriorating (of course she did.) The family wouldn't allow painkillers, because those worsen constipation, and of course, they refused to acknowledge this constipation was because of her rampant cancer they opted to leave untreated, not because of some magic nutritional deficiency. Which means no opiates - because any minute now we're going to cure that constipation with the magic vitamin.
So we had to listen to her scream, then moan, then quietly writhe. For days. While the family insisted we just find the right vitamin. Until the family insisted we try spoon-feeding her, because there just isn't the right IV feed for her. We refused. They fed her themselves. This lady who hasn't passed stool in two-odd weeks promptly vomited, aspirated, and within a few hours was in the ICU for a chemical pneumonitis.
We got to watch her die. We got to visit every-day. We got to try to gladhand the family and give them bland cliches because we didn't want them to hurt more. We didn't want to rub it in that they killed their mother.
But we got to watch it. In detail. I had the dismal, terrible pleasure of pronouncing her dead.
I'm not afraid of the terribly scary management of a vitamin C infusion in a terminal patient. I'm hurt. I'm pained. I suffer every time I have to watch preventable misery and death because a patient and/or their loved one's are busy chasing Google MD's endless font of nonsense. And because I'm not a goddamned robot, I dislike suffering, and those people that force me through more.
Surprisingly, doctors take a lot of solace in "we did what we could for her. We made it as painless as possible. We gave her as many days as we could." That means a lot. And when it's taken away from us, holy shit, do we hate it.
This was pretty stream-of-consciousness. I'm not editing it, and I'm not coming back to it, so if anyone bothers responding, know it's not for me.
I find it odd that you're focussing on making people understand that many in your profession care. It has been my experience that most health care providers… care.
Let's suppose that health care is like any other profession - let's say it's just like programming, something most people understand deeply on here.
We all know programmers who care and programmers who don't care. The best programmers I know are the ones who care, are competent, but also able and willing to have their understanding of the subject matter challenged. They're not married to their craft - they keep the right distance to excel at it.
The worst ones I know are those who care just as much, but are utterly incompetent. The ones who are so deep into it that they literally cannot see any other way. To them, everything is clear and obvious. They're willing, enthusiastic and overjoyed to be working. And they're wrong. There is not a codebase they touch where every hour of work they put in produces ten or twenty times as much work for others, later on.
I think caring about your craft is a force multiplier and it's a necessary one. You don't want a mindless drone who doesn't give a damn about either your health or your codebase, no matter how competent they are. To care means to have a vital part of you engaged in such a way that all that you could bring to the table does get there. But it has to be lightly held and accepting of being challenged.
You care. I get it. But that doesn't mean everybody cares. (Again, really struggling here to not respond in kind with examples of people I have met who clearly did not care.) And even if everybody did care - some people are actually more useless the more they care.
But - it's up to the customers (or patients) to navigate that landscape. There has to be a mutual understanding that all parties involved are just human and can make mistakes. Our understanding of health care moves forward and things that are standard care today had to be invented, sometimes just a few years ago, often replacing things that used to be just as firmly a standard, before. Challenging what is accepted practice should be a healthy part of this interaction.
There's a limit to how many people care. There is a limit to how useful it is that people care. There is a limit to how effective you can be for your patients when you walk around with a chip on your shoulder, thinking that people just don't get how much you care.
I'll freely admit that I could be self-serving in this. I didn't call into question the legitimacy of what I was seeking, only the response I got. Without dragging you through the whole process I'll say that I spent a year getting educated as best i could and 5-6 months gathering information on four adjunct therapies that I wanted her oncologist to consider adding to her existing plan. The two primary ones were this one (IVC) and the use of metformin to help manage her slowly elevating hyperglycemia. I wasn't forceful, I didn't 'sneak anything in' and I tried to avoid any outright conflict because my wife loved her doc, and I do believe her doc loved her.
As far as me being wrong, it's entirely possible, but I don't believe we're seeing my argument the same way. I do believe you care, and I do believe my wife's doc cared for her. Hell her doc cried more in our meetings than my wife did. But I care too, and while I'm not a doctor I'm also not a fucking moron. I'm a reasonably intelligent person that is tremendously invested in ensuring my wife gets the best care possible and that we maximize her quality and quantity of life as best we can. I easily have a thousand hours of crash course research and self-education into the underlying molecular genetics and microbiology...which granted pales in comparison to what MDs have, but it's not mommy blogs. I also educated myself on the various historical treatment approaches for cancer, why they went out of practice, present day standard of care and reviewed applicability and inclusion/exclusion criteria for hundreds of clinical trials around the world. I spoke with about a dozen principal investigators and 30-40 trial coordinators from MD Anderson, MSK, Johns Hopkins, Cleveland Clinic and a couple hospitals in the Netherlands and Germany. I had conversations with numerous drug and device manufacturers and actually got access to a few off-label drugs through Care Oncology (never used). I brought everything I thought would help my wife to her doctor and got zero consideration in return. No explanation, no real research into what I was suggesting, just 'not standard of care' and handwavey concerns around potential negative impacts to her therapy.
Why did I get this result? It's entirely possible she seriously considered what I asked for, maybe she spent a whole week doing her own follow-up research on my suggestions and came to the conclusion that we arrived at, but fuck me if it didn't feel like anything more than a dismissal with prejudice.
So I'm trying to find a way to reconcile that behavior with what I do feel was her care for my wife. And the only thing I can come up with is that the system she is operating under doesn't allow for her to take any risks...regardless of the patients willingness to do so. It's also possible that she's just scared that she's already on a razor's edge and anything weird coming in will not work in my wife's favor. Goes back to my fear statement, but in a different way. That said, sometimes you have to leap to survive, my wife's doc never leaped, and my wife did not survive.
About two years ago I started punctuating stressful work meetings with 'come on folks, we're not saving lives here'. It never occurred to me before to be honest, but i started out of respect of the decisions that I saw doctors making every day in my wife's care and the care of others. It's not an enviable position in my eyes, kind of hard to win when you're in oncology, and I do appreciate the fact that people sign up for it every day. I just want to get some of these bugs out of the system and empower people to have some agency in their own care. Maybe it doesn't work out, but at least they have the option to try.
Trying random things that "might work" is a great way to get hit with a malpractice case.
That being said I think you're making a huge unfounded leap in interpreting their responses. What you're describing sounds like me on a customer support call when presented with evidence that my diagnosis of a software issue was wrong. My mind races, goes back to first principles (small words), I sit up and dial up my professionalism. I also can't help but wonder as to the reliability of the customer. I'm the expert in my software! Who's more likely to be wrong?
It's a tough situation in software, I literally cannot imagine what it's like when someone's life is on the line.
Best wishes, and I hope you get the best medical care possible.
Please just trust me when I say that's not it. I could be wrong in my assessment, sure, but they are definitely not thinking about how to incorporate anything I suggest into treatment. It's pure 'get this guy to shut up'.
Thank you for the kind wishes.
https://medicalxpress.com/news/2020-02-high-doses-vitamin-im...
Mice produce l-Ascoribic Acid already, where humans cannot.
I would argue that guinea pigs would be a much better model, because guinea pigs, like humans don't manufacture their own vitamin C.
I would argue that testing any vitamin C therapy on animals that product their own l-ascorbic acid is a waste of time.
Maybe Linus Pauling was indeed on to something (https://en.wikipedia.org/wiki/Linus_Pauling ) with his idea of high dose IV vitamin C: skipping the article as it seems to take political positions ("But if this work makes some headlines of the “Linus Pauling was right” sort, don’t believe them") and using Wikipedia as a source instead:
Pauling's work on vitamin C in his later years generated much controversy. He was first introduced to the concept of high-dose vitamin C by biochemist Irwin Stone in 1966. After becoming convinced of its worth, Pauling took 3 grams of vitamin C every day to prevent colds.[13] Excited by his own perceived results, he researched the clinical literature and published Vitamin C and the Common Cold in 1970. He began a long clinical collaboration with the British cancer surgeon Ewan Cameron in 1971 on the use of intravenous and oral vitamin C as cancer therapy for terminal patients.[143] Cameron and Pauling wrote many technical papers and a popular book, Cancer and Vitamin C, that discussed their observations. Pauling made vitamin C popular with the public[144] and eventually published two studies of a group of 100 allegedly terminal patients that claimed vitamin C increased survival by as much as four times compared to untreated patients
(...)
medical establishment concluded that his claims that vitamin C could prevent colds or treat cancer were quackery.[13][151] Pauling denounced the conclusions of these studies and handling of the final study as "fraud and deliberate misrepresentation",[152][153] and criticized the studies for using oral, rather than intravenous vitamin C[154] (which was the dosing method used for the first ten days of Pauling's original study
I think we are forgetting the most important result there: vitamin C IV in high doses fights cancer.
No, that's wrong. Vitamin C IV in high doses makes certain chemotherapy work better to fight cancer. And does so in a way that Pauling wouldn't have been able to predict, his mechanism of action would imply that it would reduce the effectiveness of the chemotherapy.
see also "living proof" a New Zealand 60-minutes segment