Dietary Supplement Use During Chemotherapy and Survival Outcomes of Patients With Breast Cancer Enrolled in a Cooperative Group Clinical Trial (SWOG S0221)
"RESULTS There were indications that use of any antioxidant supplement (vitamins A, C, and E; carotenoids; coenzyme Q10) both before and during treatment was associated with an increased hazard of recurrence (adjusted hazard ratio [adjHR], 1.41; 95% CI, 0.98 to 2.04; P = .06) and, to a lesser extent, death (adjHR, 1.40; 95% CI, 0.90 to 2.18; P = .14). Relationships with individual antioxidants were weaker perhaps because of small numbers. For nonantioxidants, vitamin B12 use both before and during chemotherapy was significantly associated with poorer disease-free survival (adjHR, 1.83; 95% CI, 1.15 to 2.92; P < .01) and overall survival (adjHR, 2.04; 95% CI, 1.22 to 3.40; P < .01). Use of iron during chemotherapy was significantly associated with recurrence (adjHR, 1.79; 95% CI, 1.20 to 2.67; P < .01) as was use both before and during treatment (adjHR, 1.91; 95% CI, 0.98 to 3.70; P = .06). Results were similar for overall survival. Multivitamin use was not associated with survival outcomes."
use of any antioxidant supplement (vitamins A, C, and E; carotenoids; coenzyme Q10) both before and during treatment was associated with an increased hazard of recurrence
Dietary Supplement Use During Chemotherapy
This study supports what Daniel and others have said here many times. Chemotherapy often kills the cells by the creation of free radicals (oxidants) inside the cancer cells and this kills them. If the patient loads the cancer cells with anti-oxidants before the chemo then the cancer cells are protected against the effrects form these free radicals and don't die.
For nonantioxidants, vitamin B12 use both before and during chemotherapy was significantly associated with poorer disease-free survival
I cannot think of an explanation for the negative effects of B12.
Use of iron during chemotherapy was significantly associated with recurrence
Iron is extremely important for all cells to grow and function. As a result, the body can used both to fight and to fuel cancer.
I think that moving within safety as Daniel always advise and avoiding antioxidant adjuvants to chemo therapy.
The debate arises when doctors think that intravenous megadoses of vitamin C are antioxidants and not pro-oxidants as they really are. Some other molecules like curcumin or quercetin can also act as pro-oxidants in high doses if I'm not mistaken.
@manuone In my experience Curcumin works well with chemo. Intravenous has been used with good results a few days after chemo. Same with oral version. Actually, at this point I am in contact with someone with pancreatic cancer seeing good results and they use high dose Omega 3, high dose Curcumin, Metformin and Doxy around chemo to increase effectiveness.
As mentioned here https://www.cancertreatmentsresearch.com/modulating-the-yin-and-yang-energy-of-cells-to-fight-cancer-pro-oxidant-strategy/ the antioxidants I would be careful with and avoid during chemo are those like NAC, ALA, GSH, Vitamin E. The others I would just distance them some days away from chemo. Many of them known as anti-oxidants in the lab they are pro-oxidants in human body at cellular level in tumors.
Here is an example of a discussion on pro-oxidant mechanisms related to plant food constituents such as polyphenols due to e.g.
- dose and/or
- their interaction with metal ions e.g. Iron, Cooper ions and/or (often present in higher amount in cancer cells)
- pro-oxidant activity in a higher pH environment (which is the case for cancer cells):
In addition to the concentration of antioxidants, the presence of metal ions has been reported to play an important role. It was revealed that EGCG in the presence of transition metals causes oxidative damage to isolated and cellular DNA.53 Dietary antioxidants such as phenolics can display prooxidant activities in the presence of metal ions owing to their reducing capacity and forming chelates, such as with the transition metals iron and copper, which are important properties of these compounds in plants.3,47,48,53 The mechanism of the antioxidative action of natural compounds is considered as primary when antioxidants act directly on free radicals (-R-) by a scavenging process characterized by the donation of hydrogen atoms (resulting in the formation of -RH) or electrons (resulting in the formation of -R-).60–62 It is secondary, when the antioxidants absorb UV radiation or intervene in anti-oxidation processes as chelators of transition metal ion catalysts, act as deactivators of singlet oxygen (1O2) or convert hydroperoxides (ROOH) to non-radical species.60–63 However, the strong reducing power of antioxidants may also affect metal ions, especially Fe3+ and Cu2+, increasing their ability to form highly reactive hydroxyl radical concentrations, potentially harmful radicals, originating from peroxides via the Fenton (2) reaction.7,10Antioxidant (AH) + Fe3+(or Cu2+) → A•+ Fe2+(or Cu+) + H+(1)H2O2+ Fe2+(or Cu+) → •OH +O-H + Fe3+(or Cu2+)(2)
Such conditions could be problematic in organisms overloaded by iron as in the case of hemochromatosis,7 a disease characterized by increased iron absorption and storage from the diet. As a consequence, the metal chelating activity of several phenolics may result in the reduction of the prooxidant capacity of metal ions, however, phenolics may also act as prooxidants by chelating metals in a manner that maintains or increases their catalytic activity.48 In vitro, it has been shown that the pH influences oxidoreductions of phenolic compounds, suggesting that the pH of biological tissues could impact antioxidant/prooxidant activities of phenolics and their chelating activity. For example, a decrease in pH causes a reduced chelating effect of phenolics toward iron, possibly due to increased solubility of the complexes.48,64 The effect of pH could however be different for various phenolics. While at pH 7.4 certain phenolics have displayed prooxidant activities which at lower pH (5.8) were reported to possess antioxidant properties (e.g., γ-resorcyclic acid), others have exhibited antioxidant activities (e.g., hydrobenzoic acid).48,64
Antioxidant phenolics, when scavenging free radicals, can form less reactive phenoxyl radicals, which are stabilized by delocalization of unpaired electrons around the aromatic ring.11 However, even though these radicals are relatively stable, they can also display prooxidant activities inducing cellular damage (reviewed in ref. 53). It is well established that one of the chemopreventive mechanisms of polyphenols (or fruits and vegetables rich in antioxidants) against cancer development is the inhibition of initiation, the first step of carcinogenesis occurring following oxidative DNA damage leading to mutagenesis.27,65,66 In a recent review, the prooxidant activity of individual dietary polyphenols and their ability to induce mitochondrial dysfunction and consequently apoptosis has been suggested as a possible anticancer mechanisms.53
So I would really make the distinction between two groups of anti-oxidants. Putting everything into the same bucket would lead to loss of value.
Great information on how plant and other compounds may be antioxidant and some doses/situations and pro-oxidant in others. To add to that, I think we often want to allocate the role of a compound to antioxidant or pro-oxidant, but plant compounds often work on anti-cancer mechanisms unrelated to antioxidant status that have to do with gene regulation and cell signaling.
For example, EGCG influences VEGF, IGF1, PI3K, MMP etc and Curcumin influences PI3K, Akt, MAPK, p53 and others.
Of course, you know this, but I thought I would enter it into the conversation 🙂