Antioxidant rich foods (tea, chocolate, berries etc.) increase risk of some cancers

[TomBAvoider]

This is a pretty disturbing study - especially relevant to most on this board, as most probably take in more of these antioxidants rich foods than the average population. I do all of it (green rather than black tea, cacao powder rather than chocolate), I take in a ton of berries, and generally F&V, nuts, coffee etc. 

As I've repeatedly mentioned over the years, it's not just anti-oxidants, there is such a thing as *too many* polyphenols in the diet - and we are prime candidates for this danger. 

Gut biome strikes again. It's one of those "can't win" situations I'm afraid. That's why personalized medicine is so key - one of the reasons we take in so many F&V and nuts and berries and so on, is because large studies show benefits at the population levels. But as an individual, you may be guarding against the wrong thing - on balance perhaps it makes sense for someone who is prone to poor vascular function to take in polyphenols from cacao. But if you happen to have good vascular function (naturally low LDL cholesterol etc.), you may be better off cutting out things like cacao and instead watching your intake of antioxidant foods as you have a different vulnerability. If you have naturally low cholesterol, you don't need to ingest functional foods that lower LDL cholesterol - there is always some price to pay. Pay the price of the insurance for what you are actually vulnerable to - it doesn't make sense to pay insurance for hurricanes in CA and earthquake in FL - it doesn't benefit you and depletes your budget. Same here. Personalized medicine can't come soon enough... although it won't be here for the forseeable future - too late for anyone reading this board, sadly. 

Antioxidant-rich foods like black tea, chocolate, and berries may increase risk for certain cancers, new study finds

"What's in this flora that makes colon cancer spread so quickly? A close analysis identified the culprit: gut flora that produces metabolites, aka "antioxidants", which are found in high concentrations in foods such as black tea, hot chocolate, nuts and berries. Tellingly, when the scientists fed mice an antioxidant-rich diet, their gut flora accelerated p53's cancer-driver mode. This finding is of particular concern to those patients with a family history of colorectal cancer.

"Scientifically speaking, this is new territory. We were astonished to see the extent to which microbiomes affect cancer mutations—in some cases, entirely changing their nature," shared Ben-Neriah. Looking towards the future, those at high-risk of colorectal cancer may want to screen their gut-flora more frequently and think twice about the foods they digest, antioxidant and otherwise."

[Saul]

8 minutes ago, TomBAvoider said:

This is a pretty disturbing study - especially relevant to most on this board, as most probably take in more of these antioxidants rich foods than the average population. I do all of it (green rather than black tea, cacao powder rather than chocolate), I take in a ton of berries, and generally F&V, nuts, coffee etc. 

As I've repeatedly mentioned over the years, it's not just anti-oxidants, there is such a thing as *too many* polyphenols in the diet - and we are prime candidates for this danger. 

Gut biome strikes again. It's one of those "can't win" situations I'm afraid. That's why personalized medicine is so key - one of the reasons we take in so many F&V and nuts and berries and so on, is because large studies show benefits at the population levels. But as an individual, you may be guarding against the wrong thing - on balance perhaps it makes sense for someone who is prone to poor vascular function to take in polyphenols from cacao. But if you happen to have good vascular function (naturally low LDL cholesterol etc.), you may be better off cutting out things like cacao and instead watching your intake of antioxidant foods as you have a different vulnerability. If you have naturally low cholesterol, you don't need to ingest functional foods that lower LDL cholesterol - there is always some price to pay. Pay the price of the insurance for what you are actually vulnerable to - it doesn't make sense to pay insurance for hurricanes in CA and earthquake in FL - it doesn't benefit you and depletes your budget. Same here. Personalized medicine can't come soon enough... although it won't be here for the forseeable future - too late for anyone reading this board, sadly. 

Antioxidant-rich foods like black tea, chocolate, and berries may increase risk for certain cancers, new study finds

 "What's in this flora that makes colon cancer spread so quickly? A close analysis identified the culprit: gut flora that produces metabolites, aka "antioxidants", which are found in high concentrations in foods such as black tea, hot chocolate, nuts and berries. Tellingly, when the scientists fed mice an antioxidant-rich diet, their gut flora accelerated p53's cancer-driver mode. This finding is of particular concern to those patients with a family history of colorectal cancer.

"Scientifically speaking, this is new territory. We were astonished to see the extent to which microbiomes affect cancer mutations—in some cases, entirely changing their nature," shared Ben-Neriah. Looking towards the future, those at high-risk of colorectal cancer may want to screen their gut-flora more frequently and think twice about the foods they digest, antioxidant and otherwise."

Hmmmm.....

No information on the size of the study, whether it was conducted on humans or mice, no "p< [whatever]" information

Seems unlikely to have been done in humans -- the kind of tests they were using require informed consent.  And mice are much more prone to cancer than humans.

  --  Saul

[Dean Pomerleau]

The article Tom discusses is from Nature [1]. It is a pretty low-level mechanistic study, involving isolated (mice) cells and genetically mutant mice - a long way from humans.

I'd take it with a big pinch of salt, since recent meta-analyses of human studies e.g. [2][3] have found a consistent inverse relationship with dietary antioxidant intake and cancer, including specifically colorectal cancer [2]. Interestingly, Tom's study seems to predict that antioxidants will specifically promote cancer in the colon, but study [4] found an antioxidant-rich diet to be associated with reduce colon cancer risk, but higher rectal cancer risk.

Again it's a proponderence of evidence situation. I'm not stopping my intake of antioxidant-rich foods, or holding my breath for personalized medicine.

--Dean

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[1] Nature (2020) Published: 29 July 2020

The gut microbiome switches mutant p53 from tumour-suppressive to oncogenic

Eliran Kadosh, Irit Snir-Alkalay, Avanthika Venkatachalam, Shahaf May, Audrey Lasry, Ela Elyada, Adar Zinger, Maya Shaham, Gitit Vaalani, Marco Mernberger, Thorsten Stiewe, Eli Pikarsky, Moshe Oren & Yinon Ben-Neriah 

Abstract
Somatic mutations in p53, which inactivate the tumour-suppressor function of p53 and often confer oncogenic gain-of-function properties, are very common in cancer1,2. Here we studied the effects of hotspot gain-of-function mutations in Trp53 (the gene that encodes p53 in mice) in mouse models of WNT-driven intestinal cancer caused by Csnk1a1 deletion3,4 or ApcMin mutation5. Cancer in these models is known to be facilitated by loss of p533,6. We found that mutant versions of p53 had contrasting effects in different segments of the gut: in the distal gut, mutant p53 had the expected oncogenic effect; however, in the proximal gut and in tumour organoids it had a pronounced tumour-suppressive effect. In the tumour-suppressive mode, mutant p53 eliminated dysplasia and tumorigenesis in Csnk1a1-deficient and ApcMin/+ mice, and promoted normal growth and differentiation of tumour organoids derived from these mice. In these settings, mutant p53 was more effective than wild-type p53 at inhibiting tumour formation. Mechanistically, the tumour-suppressive effects of mutant p53 were driven by disruption of the WNT pathway, through preventing the binding of TCF4 to chromatin. Notably, this tumour-suppressive effect was completely abolished by the gut microbiome. Moreover, a single metabolite derived from the gut microbiota—gallic acid—could reproduce the entire effect of the microbiome. Supplementing gut-sterilized p53-mutant mice and p53-mutant organoids with gallic acid reinstated the TCF4–chromatin interaction and the hyperactivation of WNT, thus conferring a malignant phenotype to the organoids and throughout the gut. Our study demonstrates the substantial plasticity of a cancer mutation and highlights the role of the microenvironment in determining its functional outcome.

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[2] Crit Rev Oncol Hematol. 2019 Jun;138:70-86.

Dietary total antioxidant capacity and risk of cancer: a systematic review and meta-analysis on observational studies

Mohammad Parohan 1, Alireza Sadeghi 2, Seyed Reza Khatibi 3, Morteza Nasiri 4, Alireza Milajerdi 5, Mahmoud Khodadost 6, Omid Sadeghi 7

Abstract
Background: Recent studies have shown that dietary total antioxidant capacity (D-TAC) may affect risk of cancer; however, findings are conflicting. Hence, we aimed to summarize the current evidence on the association between D-TAC and risk of cancer.

Methods: We searched the online databases of PubMed, ISI Web of Science, Scopus, ProQuest, Science Direct and Embase until October 2018 using relevant keywords. To pool data, fixed- or random-effects models were used where appropriate.

Results: In total, 19 studies including 8 prospective and 11 case-control studies with 721429 individuals and 16159 cases of cancer were included in the current systematic review and meta-analysis. Combining 15 effect sizes from 6 prospective and 8 case-control studies revealed a significant inverse association between D-TAC (obtained from ferric reducing antioxidant power (FRAP)) and risk of cancer (combined effect size: 0.86, 95% CI: 0.81-0.92, P < 0.001). Such inverse association was also seen for D-TAC obtained from other methods including trolox equivalence antioxidant capacity (TEAC) (combined effect size: 0.80, 95% CI: 0.70-0.90, P < 0.001), total radical trapping antioxidant parameter (TRAP) (combined effect size: 0.69, 95% CI: 0.62-0.78, P < 0.001) and oxygen radical absorbance capacity (ORAC) (combined effect size: 0.72, 95% CI: 0.52-1.00, P = 0.04). In addition, a significant non-linear association was found between D-TAC (based on FRAP and TRAP) and cancer risk (P-nonlinearity<0.001). Based on linear dose-response meta-analysis, a-10 mmol/day increase in FRAP and a-5 mmol/day increase in TRAP and TEAC were associated with 9%, 17% and 14% reduction in risk of cancer, respectively. Furthermore, D-TAC was inversely associated with risk of colorectal (combined effect size: 0.82, 95% CI: 0.75-0.89, P < 0.001), gastric (combined effect size: 0.63, 95% CI: 0.53-0.73, P < 0.001), and endometrial cancer (combined effect size: 0.78, 95% CI: 0.69-0.89, P < 0.001).

Conclusions: Diet with high antioxidant capacity might have protective effects against cancer.

PMID: 31092388 DOI: 10.1016/j.critrevonc.2019.04.003

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[3] Eur J Nutr. 2019 Sep;58(6):2175-2189. doi: 10.1007/s00394-019-01922-9. Epub 2019 Feb 11.

Dietary total antioxidant capacity and mortality from all causes, cardiovascular disease and cancer: a systematic review and dose-response meta-analysis of prospective cohort studies

Mohammad Parohan 1, Javad Anjom-Shoae 1, Morteza Nasiri 2 3, Mahmoud Khodadost 4 5, Seyed Reza Khatibi 6, Omid Sadeghi 7 8

Abstract
Purpose: No conclusive information is available about the association between dietary total antioxidant capacity (DTAC) and risk of mortality. Current meta-analysis of prospective cohort studies was done to summarize available findings on the association between DTAC and risk of death from all-cause, cancer and cardiovascular diseases (CVDs).

Methods: Online databases were searched to detect relevant publications up to January 2018, using relevant keywords. To pool data, either fixed-effects or random-effects model was used. Furthermore, linear and non-linear dose-response analyses were also done.

Results: In total, five prospective studies were included in the current systematic review and meta-analysis. In a follow-up period of 4.3-16.5 years, there were 38,449 deaths from all-cause, 4470 from cancer and 2841 from CVDs among 226,297 individuals. A significant inverse association was found between DTAC and all-cause mortality (combined effect size: 0.62, 95% CI 0.60-0.64). Such finding was also seen for cancer (combined effect size: 0.81, 95% CI 0.75-0.88) and CVD (combined effect size: 0.71, 95% CI 0.63-0.82) mortality. Findings from linear dose-response meta-analysis revealed that a 5 mmol/day increment in DTAC based on ferric reducing antioxidant power (FRAP) and oxygen radical absorbance capacity (ORAC) was associated with 7% and 15% lower risk of all-cause mortality, respectively. Based on findings from non-linear dose-response meta-analysis, a significant reduction in risk of all-cause mortality was seen when increasing FRAP from 2 to 12 mmol/day (P-nonlinearity = 0.002) and ORAC from 5 to 11 mmol/day (P-nonlinearity < 0.001).

Conclusions: Adherence to diet with high total antioxidant capacity was associated with decreased risk of death from all-cause, cancer and CVDs

PMID: 30756144 DOI: 10.1007/s00394-019-01922-9

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[4] PLoS One. 2015 Nov 13;10(11):e0142995. doi: 10.1371/journal.pone.0142995. eCollection 2015.

Dietary Total Antioxidant Capacity and Colorectal Cancer in the Italian EPIC Cohort

Marilena Monica Vece 1 2, Claudia Agnoli 2, Sara Grioni 2, Sabina Sieri 2, Valeria Pala 2, Nicoletta Pellegrini 3, Graziella Frasca 4, Rosario Tumino 4, Amalia Mattiello 5, Salvatore Panico 5, Benedetta Bendinelli 6, Giovanna Masala 6, Fulvio Ricceri 7 8, Carlotta Sacerdote 8, Vittorio Krogh 2

Abstract

Background: Colorectal cancer is the third most common cancer worldwide. Diet has been hypothesized as involved in colorectal cancer etiology, but few studies on the influence of total dietary antioxidant intake on colorectal cancer risk have been performed.

Methods: We investigated the association between colorectal cancer risk and the total antioxidant capacity (TAC) of the diet, and also of intake of selected antioxidants, in 45,194 persons enrolled in 5 centers (Florence, Naples, Ragusa, Turin and Varese) of the European Prospective Investigation into Cancer and Nutrition (EPIC) Italy study. TAC was estimated by the Trolox equivalent antioxidant capacity (TEAC) assay. Hazard ratios (HRs) for developing colorectal cancer, and colon and rectal cancers separately, adjusted for confounders, were estimated for tertiles of TAC by Cox modeling, stratifying by center.

Results: Four hundred thirty-six colorectal cancers were diagnosed over a mean follow-up of 11.28 years. No significant association between dietary TAC and colorectal cancer incidence was found. However for the highest category of TAC compared to the lowest, risk of developing colon cancer was lower (HR: 0.63; 95% CI: 0.44-0.89, P trend: 0.008). By contrast, increasing TAC intake was associated with significantly increasing risks of rectal cancer (2nd tertile HR: 2.09; 95%CI: 1.19-3.66; 3rd tertile 2.48 95%CI: 1.32-4.66; P trend 0.007). Intakes of vitamin C, vitamin E, and ß-carotene were not significantly associated with colorectal cancer risk.

Conclusions: Further prospective studies are needed to confirm the contrasting effects of high total antioxidant intake on risk of colon and rectal cancers.

PMID: 26565695 PMCID: PMC4643904 DOI: 10.1371/journal.pone.0142995