Antioxidants have shown toxicity to cells, even differential for cancer and normal cells.
Hydrophobic lipophilic antioxidants in non-physiological concentrations are always toxic for cells excepting cells that are able to accumulate them, for example, Ito cells. Cancer cells often have an ability to do it too and in general it is appropriate to them to accumulate low-molecular antioxidants for non-specific defence.
Hi Krishnanand,
Yes, overdosing certain AO under special circumstances can lead to the generation of free radicals. This can happen in a direct (Vit E, eg) or indirect (Vit C, eg.) manner.
Vit C increases the intestinal absorption of iron and other metals, and these metals have pro-oxidative effects on lipids.
Carr and Frei, Does vitamin C act as a pro-oxidant under physiological conditions?
The FASEB Journal, 1999, 1007-1024
A good overview on different nutrition relevant AO and their pro-oxidative capacity is provided in this review:
Rietjens et al. The pro-oxidant chemistry of the natural antioxidants vitamin C, vitamin E, carotenoids and flavonoids, Environmental Toxicology and Pharmacology, 2002, 321-333
All mentioned possible pro-oxidative properties of AO are only observed after supplementation or fortification. Unprocessed and natural food have never shown this pro-oxidative effects.
Yeh, also it's well-known redox-paradox when under pro-oxidant conditions antioxidant supplementation resulted in increase of pro-oxidant activity
Could too much anti-oxidant impede oxidative phosphorylation in the mitochondria? I imagine the concentrations required for this would be very high, and maybe these other things daria and olivier mentioned would occur first.
Hi Daria, u look nice.
u commented well but how ? not answered well, i mean how they are toxic....though it is beneficial also....i want more....
What type of ao are you talking about? Ao have more than one type of classes depending on mechanism of action.
Good point Krishnanand !
I agree with Apurva K., because Ao have different chemical stucture and also mecanism of action.
I didn't talk that AO have just negative effects. But, as to pro-oxidant effects of AO, especially vitamins, you can read these reviews, for example:
Carr A, Frei B. Does vitamin C act as a pro-oxidant under physiological conditions?FASEB J. 1999 Jun;13(9):1007-24.
Podmore ID, Griffiths HR, Herbert KE, Mistry N, Mistry P, Lunec J. Vitamin C exhibits pro-oxidant properties.Nature. 1998 Apr 9;392(6676):559.
Pearson P, Lewis SA, Britton J, Young IS, Fogarty A. The pro-oxidant activity of high-dose vitamin E supplements in vivo.BioDrugs. 2006;20(5):271-3.
Poljsak B, Raspor P. The antioxidant and pro-oxidant activity of vitamin C and trolox in vitro: a comparative study.J Appl Toxicol. 2008 Mar;28(2):183-8.
Rietjens IM, Boersma MG, Haan Ld, Spenkelink B, Awad HM, Cnubben NH, van Zanden JJ, Woude Hv, Alink GM, Koeman JH. The pro-oxidant chemistry of the natural antioxidants vitamin C, vitamin E, carotenoids and flavonoids. Environ Toxicol Pharmacol. 2002 Jul;11(3-4):321-33.
Also, it was proved in clinical trials that AO treatment doesn't have benefits in treatment of cardiovascular decease and in some cases this therapy results in decrease of life span and increase of mortality:
For example
Thomson MJ, Puntmann V, Kaski JC. Atherosclerosis and oxidant stress: the end of the road for antioxidant vitamin treatment? Cardiovasc Drugs Ther. 2007 Jun;21(3):195-210.
I think that chemical structure of true antioxidants (I mean its ability to be reduced and oxidized) determines its pro-oxidant potential under non-physiological conditions
As to cancer cells - the same situation - in some cases AO is good and anti-cancer, in other ones - AO supplementation results in stimulation of cancer progression.
Example, of course
Sakagami H, Satoh K, Hakeda Y, Kumegawa M. Apoptosis-inducing activity of vitamin C and vitamin K. Cell Mol Biol (Noisy-le-grand). 2000 Feb;46(1):129-43.
I think that one also should consider the stability of the antioxidants during treatments. In many cases reseraches detect effect of not compound itself, but effects of degradations products. For example, Vit C (Ascornbate) is very unstable and demonstrated rapid degradation to DHA and later on to other toxic compounds. Similar picture is true for the other low molecular weight antioxdants. Moreover, high artificail antixoidants level (after tretament) may lead to disturbtion of internal antioxidant machinery. This may lead to toxic effect after degradation of exteranl antioxidants.
Good luck!
Some antioxidants have powerful pro-oxidant activities; this mostly depends on the concentration and availability of other factors like trace elements (Cu, Zn, Fe) in free form, or any substance that potentially has the ability to participate in Oxidation-Reduction reactions in the biological system.
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