Merged Antioxidant Supplements and Cancer Risk

blutoski

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blutoski
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I try to keep current on any new developments in immunology, and this study came across my study group yesterday:


Abstract:
Antioxidants are widely used to protect cells from damage induced by reactive oxygen species (ROS). The concept that antioxidants can help fight cancer is deeply rooted in the general population, promoted by the food supplement industry, and supported by some scientific studies. However, clinical trials have reported inconsistent results. We show that supplementing the diet with the antioxidants N-acetylcysteine (NAC) and vitamin E markedly increases tumor progression and reduces survival in mouse models of B-RAF- and K-RAS-induced lung cancer. RNA sequencing revealed that NAC and vitamin E, which are structurally unrelated, produce highly coordinated changes in tumor transcriptome profiles, dominated by reduced expression of endogenous antioxidant genes. NAC and vitamin E increase tumor cell proliferation by reducing ROS, DNA damage, and p53 expression in mouse and human lung tumor cells. Inactivation of p53 increases tumor growth to a similar degree as antioxidants and abolishes the antioxidant effect. Thus, antioxidants accelerate tumor growth by disrupting the ROS-p53 axis. Because somatic mutations in p53 occur late in tumor progression, antioxidants may accelerate the growth of early tumors or precancerous lesions in high-risk populations such as smokers and patients with chronic obstructive pulmonary disease who receive NAC to relieve mucus production.
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This is consistent with the body of literature to date. Both the biochemistry and in vitro research strongly imply that antioxidant supplementation carries a risk of increased cancer.

There are a few human studies that show the same effect, *but* those studies were not designed to look for that effect, and so I hesitate to say there are human studies that actually show this effect.

So, this is my question: does anybody on the list with the appropriate qualifications think I'm out to lunch by saying it's time to shift antioxidant supplementation from the 'what's the harm' category to the 'proven harmful' category?
 
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Based on a single study with mice? ???

No. It's still widely unproven.

Side note: don't you love how these studies put things in plain English :rolleyes:
 
bigred said:
Based on a single study with mice? ???
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I want to reiterate that I always try to fit any new study into the existing literature and sift for quality.

This is not the first study of its kind (mouse), and the authors are specifically measuring the cancer growth endpoint (as opposed to discovering a relationship after the fact) and concentrating on specific mechanisms they know are analogous to human physiology, so we put it in the 'accept' pile. At this point I and my immunology study group have consumed about 300 studies on this topic and we've put about 15 in the 'accept' pile. This is one of them.



bigred said:
No. It's still widely unproven.
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Just to clarify: do you mean unproven or disproven?



bigred said:
Side note: don't you love how these studies put things in plain English :rolleyes:
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I didn't understand that. Were you saying you think they're dumbing the abstract down so it's more publishable?
 
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I read an article a while back suggesting pretty much the same thing - that there is quite a fine natural balance in metabolising cells in vivo between the creation of free radicals and antioxidants, that varies according to context; e.g. free radical generation is thought to increase in response to cancer cell growth or other invasive growth (bacteria, viruses).

The gist was that cell biochemistry relating to free radicals and antioxidants was part of a complex homeostatic system and that ad-hoc input of large quantities of antioxidants might well be a disruptive influence on this system rather than than the generally beneficial influence assumed by many.
 
dlorde said:
I read an article a while back suggesting pretty much the same thing - that there is quite a fine natural balance in metabolising cells in vivo between the creation of free radicals and antioxidants, that varies according to context; e.g. free radical generation is thought to increase in response to cancer cell growth or other invasive growth (bacteria, viruses).

The gist was that cell biochemistry relating to free radicals and antioxidants was part of a complex homeostatic system and that ad-hoc input of large quantities of antioxidants might well be a disruptive influence on this system rather than than the generally beneficial influence assumed by many.
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Another candidate mechanism to explain how antioxidants increase cancer risk is that serum antioxidants could inhibit tumour surveillance - this is what the study I referenced in the OP was investigating. The effect would be strongest on individual cells rather than tumours, and this was their finding. (this is why it remains of interest to my immunology study group - tumour surveillance via oxidation is a function of a particular class of immune cells)
 
It's my understanding that "large quantities" was pretty much beyond the reach of even a supplemented normal diet, the equivalent of mercury poisoning from eating sushi. I would class antioxidants along with most vitamin supplements, mostly ineffective but harmful in (very) high dosages.

Blutoski - I'm curious. How does the surveillance via oxidation differentiate between tissues with radically (pun intended ;) ) different baseline ROS?
 
Katdai said:
It's my understanding that "large quantities" was pretty much beyond the reach of even a supplemented normal diet, the equivalent of mercury poisoning from eating sushi. I would class antioxidants along with most vitamin supplements, mostly ineffective but harmful in (very) high dosages.

Blutoski - I'm curious. How does the surveillance via oxidation differentiate between tissues with radically (pun intended ;) ) different baseline ROS?
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The white cells (NK) are acting directly on individual tumour cells, rather than tissues.
In conjunction with macrophages, they partly bind to them and excrete peroxide and other cytokines in very close proximity. This disrupts the target cell membrane and usually destroys most of the components of its cytoplasm.

The model is that antioxidants might be weakening the exposure, and more target cells survive.
 
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Katdai said:
It's my understanding that "large quantities" was pretty much beyond the reach of even a supplemented normal diet, the equivalent of mercury poisoning from eating sushi.
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Yes, that was careless of me; by 'large quantities' I meant the significant supplementation of a normal diet.

I would class antioxidants along with most vitamin supplements, mostly ineffective but harmful in (very) high dosages.
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I think it's less about the absolute amount, but more about how much is required to have a significant effect and whether that effect is likely to be advantageous or not.
 
James Watson published a theory paper on this about a year ago. It was controversial then and I'm guessing it still is today. But I think the premise is that cancer cells use antioxidants to stay alive. So treating cancer with antioxidants is counter productive. This says nothing about preventing cancer in the first place.
 
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I think this builds also on the more recent understanding of oxidative stress being a normal metabolic challenge, if you will, to the body. That is, it is a necessary process, and the regulatory and adaptive mechanisms in the body to mitigate this may be important and should not artificially/externally interfered with.

Will be interesting to see how subsequent research pans out.

~Dr. Imago
 
Oh cmon. The "experts" have been telling us for years how antioxidants are good...and they're NEVER wrong! After all, studies were done, and they're never wrong either!

Well I'm off to chew on some acai berries.
 
I have not seen one and I tend to look for science stuff as a semi-specialty. If you find one I will happily be absorbed into it!!
 
If you eat good whole foods with lots of fresh fruits and veggies, what in the world would you need anti-oxidant supplements for?

And if you eat junk food, why in the world would you think an anti-oxidant supplement would magically make that twinkie or Corn King deep fried bacon corn dog healthy?

The whole thing is ridiculous. If for some reason you can't get good nutritious food, then OK fine, supplements can help... sometimes. Otherwise forget it.
 
Red Baron Farms said:
If you eat good whole foods with lots of fresh fruits and veggies, what in the world would you need anti-oxidant supplements for?

And if you eat junk food, why in the world would you think an anti-oxidant supplement would magically make that twinkie or Corn King deep fried bacon corn dog healthy?
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Stupidity. It's all the rage.
 
The immediacy of the Now Generation.

Rather than eating a healthy diet;

... just take supplements marketed to sort that problem - even if you don't have a medical problem
... and then pop an anti-obesity pill to counter the weight you're gaining from that over eating
... then another pill to counter that GORD problem you don't even have since all it is indigestion you get from all that overeating
... then pop another pill to stave off the heart attack that is imminent from the weight gain and lack of exercise
... you now probably should take another series of pills to counteract the side effects all these other pills and supplements will cause
... then get some cosmetic surgery done to implant where muscles would have been had you done any exercise
... blame supermarkets and advertising for all your overeating
... blame Big Pharma for all the pills you're popping
... blame everyone else for the state you are in
 
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