NAC protects from lung emphysema but induces lung adenocarcinoma in mice | Hacker News Reader

NAC protects from lung emphysema but induces lung adenocarcinoma in mice

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30 pointsbirriel17 comments

There is mounting evidence that anti-oxidant supplements are cancer promoting (or perhaps more accurately, ‘deprotecting’). A lot of this data is in animal models, but there is also a bit of high quality controlled trial data. The best example is probably that vitamin E increases the risk of prostate cancer (https://jamanetwork.com/journals/jama/fullarticle/1104493).

Proponents will argue endlessly that it isn’t the right formulation of vitamin E and nitpick trial flaws, but taken as a whole the data is pretty clear. Eating AO rich foods is fine, but I would not take a supplement.

You might think it’s a nitpick, but vitamin E is a fat soluble vitamin that usually coexists with other fat soluble vitamins. Taking any one of A,D,E,K without the others can cause problems.

That supports your concept of eating nutrient dense food. But I also think supplements can help a lot when done wisely (but most supplementation is probably not done wisely).

> Proponents will argue endlessly that it isn’t the right formulation of vitamin E and nitpick trial flaws […]

Vitamin E is not a single vitamin but is a group of eight different vitamins with different properties. Detrimental effects of large doses of α-tocopherol that was used in the study have long been implicated and cautioned about.

Need to take the literature as a whole. One can always postulate more complicated causal relationships and caveats, but in the end the question is should a random person take Vitamin E tomorrow? The answer is clearly no, for me.

A useful tool is Mendelian randomization. This looks for disease phenotypes that differ between people with different levels of vitamin E which is genetically determined. This is perfectly 'natural' vitamin E, not even a supplement.

https://bmcmedicine.biomedcentral.com/articles/10.1186/s1291... No clear association with cancer risk apparent, but seemed to increase bladder cancer risk with a large effect size.

https://www.ahajournals.org/doi/full/10.1161/JAHA.121.022567 Doesn't protect against stroke.

https://www.sciencedirect.com/science/article/abs/pii/S01974... Doesn't protect against Alzheimer's disease

It's a similar issue with Vitamin C, particularly intravenous vitamin C. Whenever a proper trial is done, it shows either not much, or harm (very significant harm recently: https://www.nejm.org/doi/full/10.1056/NEJMoa2200644).

> Need to take the literature as a whole.

The literature as a whole has not yielded conclusive results on either side of the fence yet. There are studies that have found benefecial effects of a supplement XYZ intake, and there are also studies that have found detrimental effects of the same XYZ supplement intake. We still have a poor understanding of how the body chemistry works and have an even poorer understanding of synergies or interrelationships between the intake of different «molecules». Moreover, how a particular chemical compound is going to affect to a random indiviual also largely depends on their overall health, age, sex, lifestyle and dietary habbits and a wide range of other compounding factors.

> … should a random person take Vitamin E tomorrow? The answer is clearly no, for me.

I am not advocating random people to start voraciously ingesting random things, however, the answer to such a question is far being clear. The short answer is «we don't know».

δ-tocopherol, for example, has no currently known biological role in the human body, therefore it will most likely undergo a safe passage in one's digestive tract and leave the body unharmed and without harming the body in the process. Most supplements will either give one a diarrhea or leave them constipated. Sometimes intermittently both. Lethal outcomes of the dietary supplement ingestion are not entirely unknown albeit are exceedingly rare.

There is a significant number of people out there, however, who start taking a supplement ABC expecting to develop supernatural abilities (e.g. grow a tail, acquire clairvoyance, learn the spell of casting a fireball or propel their endowment into unseen before highs) and, when nothing happens after 2-3 days, they become very disappointed or even disgruntled.

> This looks for disease phenotypes that differ between people with different levels of vitamin E which is genetically determined.

The Mendelian randomisation of the received/studied results is perfectly fine at the analytical stage of the study, however it is never a starting point of a new study. On the subject vitamin E specifically, the vast majority of studies use megadoses of α-tocopherol (400 IU or higher) that is not found anywhere in nature thus rendering study results inconclusive at best or useless at worst to the point that now most vitamin E studies can now be classified as pointless and junk, or as an easy way to obtain a research grant to later state that the study results are inconclusive and a further research is necessary.

The first study from your list, for example, focuses on measuring levels of vitamin E (only sketchily mentioning α-tocopherol levels) without quoting dietary sources (from food only or from food + supplemented?) across a random selection of samples from a blood test bank. The second study coyly mentions that «… diet‐derived antioxidants were used, which included vitamin E (α‐tocopherol and γ‐tocopherol) …» without specifying their respective sources (food or food + supplement). The third study is behind the Elsevier paywall and does not provide any meaningful details in the abstract.

One of the very first studies of vitamin E that has raised an alarm about potential harm of large doses of α-tocopherol was a Finnish one that followed a group of Finnish smokers over a succession of approximately 15 years AND supplemented them with large doses of α-tocopherol (not an abstract «vitamin E»!) throughout the entire study. The result of the study was an increased mortality across the study cohort which has been prescribed to misfortunes of the α-tocopherol intake. Yet, we still don't have a understanding of via which specific metabolical or chemical pathways α-tocopherol may influence the tumor development in the human body.

> This is perfectly 'natural' vitamin E, not even a supplement.

There is no such a thing as a «perfectly natural vitamin E» as «vitamin E» is a collective classification term for a cluster of up to 8 chemical compounds (α-, β-, γ-, δ-tocopherols and d-α-, d-β-, d-γ-, d-δ-tocotrienols) the concentration of which varies wildly across different food sources. For example, the red palm oil is unusually rich in tocotrienols whereas the soybean oil has them in nowhere near concentrations. α-tocopherol is also widely used as an officially approved food additive E306 (tocopherol) / E307 (α-tocopherol) which means that a unsuspecting broad population is exposed to an inadvertant larger intake of α-tocopherol as opposed to getting from natural source only.

So… it is complicated and far from being clear.

I’m getting the sense that the control system here is pretty tight. In that, any intervention that causes cells to change, divide, or die… pretty much causes statistically more cancer.

(As does eating barbecue, but is that not also an intervention of sorts?)

I’m sure we can fix that bug in our project of curing so much pain.

I used to think we’d be testing nanobots in patients by now, so what do I know? But I don’t think we’ve found the mutation/metabolism/mitosis sweet spot.

Save us, something we haven’t tried yet! Maybe it’s still CRISPR, and I’m just talking impatiently.

Mice most commonly die due to cancer, so it's a pretty obvious outcome when by inhibiting one type of cancer we let the animal die with another type of cancer.

There are treatments that extend mouse lifespan in experiments though, see my comment history.

For complementary medical diets for the treatment of cancer the idea is to reduce inflammation in the microenvironment around the tumor. Most complementary medicine anti-cancer diets promote high anti-oxidant, low inflammation foods and supplement regimens which include antioxidants such as NAC.

Patients on such regimens (which also included traditional chemotherapy) generally showed significantly improved survival rates compared to the control which just had the chemotherapy.

https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1524-4741....

NAC should be taken with vitamin C in a 1:3 ratio as far as I recall to avoid the development of kidney stones. So, if you get 600mg of NAC, you need 1.8g of vitamin C, which is way too much. There was a study showing mitochondrial damage of viatmin doses higher than 500mg, so your max daily NAC intake should be 167mg, which is too little to do anything as NAC alone... Or maybe supplement with a kidney stone breaker such as Chanka Piedra. Supplements are such a messy business!

I'm not sure why it would be problematic to take dosages of 2g or more of vitamin C?

Well, there was a study ("a study finds"). Anyway, jokes aside, I can dig it out, but, in general, if something is good, then taking more of it does not increase its benefits. On the contrary, every nutrient has a range, which could also vary from a person to a person, below or above those thresholds you not only are not receiving any benefits, but you can also be doing damage. Have you heard the saying "too much of a good thing"? From "kale has good nutrients", we're not selling kilos of kale juice, which, for sure, has tons of detriments especially on their pitiful thyroids!

For example, a lot of people don't know it, but vitamin C increases your blood sugar. Not to mention the other type of kidney issues with too much vitamin C.

NAC gets used by some CF patients to do topical lung treatments because people with CF have an excess of glutathione internally to their cells and a shortage on the surface, so they seek to address the surface shortage which is easier than figuring out what causes the imbalance and addressing that.

My thinking is that cells hoard it internally to buffer against deadly chemical derangement, so it's of limited use to add more to the surface.

It seems likely that cancer operates somewhat similarly.

Can anyone translate the amount of NAC the mice got into human terms? Or how the amounts given to COPD patients or the like compares to what OTC supplements have?

The article was published in 10-2019. The only reference to 'mg' (not milligrams) I can find was for magnesium chloride. Good question. The amount may be relevant, eg too much niacin, liver trouble. Too little, pellagra. Etc.

I remember Dr Seheult (of medcram) taking somewhere between 600-1200mg (daily) of NAC during the early covid pandemic. Perhaps he's posted an update on the subject.

Edit: the FDA was aiming to regulate NAC (to Rx only) in 2020-2021, resulting in Jarrow (a large producer) discontinuing it from their product line. It became difficult to find for several months, from any producer, anywhere. Many outlets removed it from inventory.

I've not read or heard anything lately. Maybe the FDA has been sidetracked with other efforts to regulate something of equal or greater evil. Rx hotdogs maybe. Prescription cigarettes. Pfizer Transfats, or... pfas marmalade.

NAC is back on Amazon, so whatever happened may have stopped.

You can buy Doctor's Best NAC pretty much everywhere.

> the risk of developing lung adenocarcinoma was increased, possibly by weakening of the tumorigenesis-barrier effect of cell senescence

The proposed mechanism of why there is an increase in lung adenocarcinoma makes sense to me:

Because of NAC and its antioxidant effects, cells were living longer in these mice; much longer than usual. While predictably, this caused lower rates of lung emphysema, it had an adverse effect of increased cancer risk due to messing with harmony of cell cycle arrest (cellular senescence).

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