Coffee, Tea, Cacao, Caffeinated Sodas & Breast Cancer: 5+ Cups/Day?! Study & Meta-Analysis Show, It May Take More Coffee Than Previously Thought to Ward Off Breast Cancer

While you don't have to bath in coffee, one cup per day is probably not enough to protect your mammary glands.

Initially today's SuppVersity post was just about coffee and breast cancer risk. Today, a couple of days and a hand full of news on other interesting papers that are piling up by dozens in my archive, I found that the paper has proliferated ;-o

Well, not exactly, but in conjunction with a recent meta-analysis on the potential anti-breast-cancer effects of coffee today's news certainly covers data from almost 380,000 women world-wide and will thus probably yield somewhat more reliable data on whatever relation may exist between a woman's coffee / caffeine consumption and her risk of developing breast cancer.

It takes Canadian women at least 5 cups of coffee to elicit significant reductions in breast cancer risk

Against that background, both the detailed 7-item sub-analysis of the data from the Women’s Diet and Health Study and the unique inclusion of information on the cytochrome P450 1A2 (CYP1A2; the enzyme that's responsible for the metabolism of caffeine) gene variant of the 25 to 74 year old women distinguish the soon-to-be-published epidemiological study by Elizabeth C. Lowcock and her Canadian (resident) who found that there is no general association with coffee and caffeine consumption on the one, and breast cancer risk on the other hand.

"[H]owever, a significant reduction in risk was observed with the highest category of coffee consumption [≥5 cups per day vs. never, multivariate-adjusted odds ratio (MVOR)=0.71, 95% confidence interval (CI): 0.51, 0.98]." (Lowcock. 2013)

Interestingly, the ~30% reduction in breast cancer risk the scientists observed in their cohort of Ontarian women, did not depend on the gene variant of the aforementioned caffeine metabolizing enzyme from the cytochrome P450 enzyme cascade. coffee consumption, but not total caffeine" (Lowcock. 2013) that's associated with a reduced risk of both estrogen receptor positive and post-menopausal breast cancers.

Figure 1: Multivariate-adjusted odds ratios for breast cancer and coffee, decaffeinated coffee and caffeine intake w/out correction for CYP1A2 (rs762551) genotype (Lowcock. 2013)

In conjunction with the actual data from the 7-item analysis, this observation supports the scientists hypothesis that it is "coffee consumption, but not total caffeine" (Lowcock. 2013) that's associated with a reduced risk of both estrogen receptor positive and post-menopausal breast cancers.

If that is true, i.e. if it's not the main active ingredient caffeine, but one of or the complete spectrum of polyphenols the dark brew has to offer, it seems logical that such an exuberant amount of coffee is necessary to benefit from the purported protective effects (remember we are still talking about associations of consumption and breast cancer incidence - not mechanisms) of coffee. Why? Well, despite the fact that a comparison on a mere weight-to-weight ratio is obviously overtly simplistic, the amount of whatever flavenoid or other ingredient may turn out to be responsible for the anti-cancer effect is almost certainly at least one, if not several magnitudes smaller than those 100-200mg of caffeine your "average" (whatever that may be today) cup of coffee has to offer.

2% risk reduction per two cups? Looks like more was really better.

The notion that "more helps more" is indeed supported by another a meta-analysis of 37 international studies, Wenjie Jiang, Yili Wu and Xiubo Jiang from the Medical College of Qingdao University in Shandong have conducted (Jiian. 2013).

Suggested read: "Only 'Real', Yet Not Decaffeinated Instant Coffee Increases Fatty Acid Oxidation. Plus: Revisited, Caffeine's Dose-Dependent Effect on the Exercise Induced Changes to the ratio of Testosterone to Cortisol" (read more)

According to the study, which is going to find it's way into one of the next issues of Gynecologic Oncology, the collective data of 966,263 study participants (59,018 breast cancer cases) does not warrant the conclusion that either coffee or caffeine consumption (yes vs. no) is associated with a significant reduction in breast cancer risk:

• coffee -- 3% risk reduction, p = 0.09
• decaffeinated coffee -- 2% risk reduction p = 0.55 
• caffeine - 1% risk reduction,  p = 0.73

In fact, the p-value, i.e. the probability that a result is mere coincidence, passes the magic p < 0.05 (meaning there is a <5% chance of the observed association being mere coincidence) hurdle only in postmenopausal coffee concessionaires, whose risk of developing breast cancer is 6% lower than that of their non-coffee guzzling peers.

What's particularly intriguing, though, is the fact that Jiang, Wu & Jiang found a linear dose-response relationship for breast cancer risk with coffee and caffeine, with

"the risk of breast cancer decreas[ing] by 2% (P=0.05) for every 2 cups/day increment in coffee intake, and 1% (P= 0.52) for every 200 mg/day increment in caffeine intake, respectively." (Jiang. 2013)

If we do the math this yield a 10% reduction in breast cancer risk for the 5 cups which gave the Canadian women a 30% edge over their non-coffee drinking peers.

In view of the fact that the number of people consuming this amount of coffee on a daily base (3% in the Women's Diet & Health Study) is in epidemiological terms comparatively low, the "small" deviation of 20% is nothing that would negate the existence of a surprisingly profound protective effect of coffee on the development of breast cancer.

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Bottom line: I don't want to be a spoilsport, but as a versed SuppVersity reader you should by now be aware that anything beyond 400-500mg of caffeine (for a woman, for a man maybe 500-600mg) can produce a couple of nasty heart and central nervous system related side effects in view of which the regular / chronic consumption of more than 5 cups of coffee is nothing I would suggest as a means of cancer protection. And since the currently available data does not confirm similar beneficial effects for decaffeinated coffee (see figure 1 red button for likely explanations), you should consider different means of breast cancer protection. Which means that would be? Well, ...

Even one cup of hot chocolate per week could help reduce your risk of developing breast cancer by 15% (learn more about the health effects of cacao & chocolate)

• cut your intake of caffeinated soft-drinks to zero and thus reduce your breast cancer risk (compared to drinking 2 cans per day) by 24% or a statistically hardly significant, but still worth mentioning -7% vs. consuming only one can per week (Lowcock. 2013)
• drink some black tea for a change, and achieve a 13% reduction in breast cancer risk with 3-5 cups per day (Lowcock. 2013)
• never pass on a delicious cup of cacao, even one cup of hot chocolate per week can decrease your breast cancer risk (due to the low number of cacao drinkers the -15% reduction is yet not significant, Lowcock. 2013)

• lose weight and visceral fat to avoid the +107% increase in breast cancer risk non-hispanic white women with a BMI >30kg/m² have compared to their non-obese fellow females (Connor. 2013)

If you work out and stick to a whole foods diet, that's about as much as you can do for the health of your mammary glands. Well,... maybe aside from taking synthetic estrogen and progestin combos to battle the symptoms of menopause (read more about this in the SuppVersity Facebook news).

References:

• Connor AE, Baumgartner RN, Pinkston C, Baumgartner KB. Obesity and Risk of Breast Cancer Mortality in Hispanic and Non-Hispanic White Women: The New Mexico Women's Health Study. J Womens Health (Larchmt). 2013 Mar 26.
• Jiang W, Wu Y, Jiang X. Coffee and caffeine intake and breast cancer risk: An updated dose-response meta-analysis of 37 published studies. Gynecol Oncol. 2013 Mar 24.
• Lowcock EC, Cotterchio M, Anderson LN, Boucher BA, El-Sohemy A. High Coffee Intake, but Not Caffeine, is Associated with Reduced Estrogen Receptor Negative and Postmenopausal Breast Cancer Risk with No Effect Modification by CYP1A2 Genotype. Nutr Cancer. 2013 Apr;65(3):398-409.

Only "Real", Not Decaffeinated Instant Coffee Increases Fatty Acid Oxidation. Revisited: Caffeine's Dose-Dependent Effects on Testosterone & Cortisol Response to Exercise

Image 1: Coffee is made of coffee beans! Hard to believe if you look at what remains of this precious superfood in a sachet with instant "coffee", right? But is instant, let alone "decaf" + instant really as bad as its rep?

Although I know that probably not everyone is going to agree with that, I personally believe that coffee is one of the few real "superfood"... if it still is coffee and not some sort of adulterated lifestyle drink with synthetic caffeine and coffee-aroma. Those of you who like to enjoy their morning coffee (or tea) with tiny dose of SuppVersity news, will probable remember the "Warding Off Holiday Weight Gain"-posts in which I already broached the issue of the metabolic benefits of real coffee. With a coffee and a caffeine arm, the said rodent study did yet not provide any clues about the benefits or downsides of "decaf", i.e. de-caffeinated coffee, the supposedly "healthier" alternative to the stimulating brown brew, which has once been a prerogative of kings and popes and has as of late been turned into a lifestyle drink by the clever marketing campaigns of Starbucks & Co.

Instant Defac before exercise? That does not make sense, right?

In their study, Donrawee Leelarungrayub, Maliwan Sallepan and Sukanya Charoenwattana from the Chiang Mai and Burapha Universities in Thailand tried to get to the bottom of the question of whether or not the acute ingestion of coffee (not caffeine or stimulant loaden pre-workout products) would exert any beneficial or detrimental effects on the energy utilization and antioxidant capacity of 26 healthy and normal-weight, but non-athletic (=mainly sedentary ;-) men. The subjects who were assigned to one out of three study groups

1. regular coffee - at a dose that would deliver 5mg/kg body weight (for a 70kg Thai this would be 350mg or 1-2 large cups of coffee)
2. decaffeinated coffee - at an identical dose, yet prepared with instant freeze dried decaffeinated  coffee from Expressor, Thailand
3. placebo - unfortunately the scientists do give any further information on the placebo group, other than stating that they received "no supplement", if this means that groups 1 and 2 ingested fluids, while group 3 did not, this would be a minor flaw in the study design

and performed a standardized exercise protocol on the treadmill where speed and slope were increased in three-minute intervals Directed VO2 and RER (respiratory exchange ration = measure of carbohydrate to fat oxidation; lower values indicate higher fat oxidation) were analysed automatically by the Breeze-Suit Software program.

Real men (and women) drink real coffee... at least if their goal is fat loss ;-)

The VO2 and RER values you see in figure 1 were taken, when the heart rate of the subjects had climbed to 80% of their maximal heart rate and could be interpreted as being indicative of what you would see during the high intensity phases of a short high intensity (yet not all out) interval training (HIIT) regimen. Unfortunately trial 1 (without coffee) and trial 2 (with coffee) were performed subsequently, it is thusly no wonder that the oxygen consumption increased and the RER dropped in all three conditions - a similar effect is seen, when you perform your "cardio" training after your resistance training sessions, when the decreased glucose availability forces your body to burn more fat.

Figure 1: Differences in VO2 consumption, respiratory exchange ratio (RER), blood glucose and malondialdehyde (MDA) in trial one (unsupplemented) vs. trial two (supplemented; data based on Leelarungrayub. 2012)

The statistical insignificance of the changes in the control and decaffeinated coffee group do yet suggest that the respective increases and decreases in the "real" coffee (with caffeine) group are independent of any kind of "priming" effect due to previous exercise - an assumption that is reinforced by the >4% higher post-exercise glucose levels (compared to the non-supplemented trial) in the caffeinated coffee trial and the oppositional decrease of the latter in the decaf and the control groups.

If you just want the antioxidant effects, decaffeinated coffee seems to be fine, though

What is yet somewhat unresting is the profound +71% increase in MDA levels in the regular coffee group. And while the change in total antioxidant capacity (TAC; not shown in figure 1) was not statistically significant in either of the groups, it is still quite telling that - all statistical shenanigan aside - the subject who consumed the decaffeinated coffee were the only ones, where the TAC values increased from the pre- (control) to the post (supplementation) test.

Image 2: If you still belive that temporary increases in testosterone build muscle and cortisol needs to be eradicated at all costs, you better (re-)read the Intermittent Thoughts

Whenever the topic "caffeine and exercise", it is more or less imperative that someone is going to ask about its effects on cortisol (and testosterone), thusly I would like to take this opportunity to briefly cite the results of one of the few studies which actually deals with the effects of different amounts of caffeine on the testosterone and cortisol responses to exercise: The study was conducted with 24 professional rugby players who were randomly assigned to receive 0, 200, 400 or 800mg of caffeine 1h before performing a standardized resistance training protocol (Beavan. 2008). Contrary to what bro-science has been suggesting for years (meanwhile many bros are aware of this study, so that this is about to change ;-) the ingestion of the lower doses 200mg and 400mg) of caffeine did not lead to statistically significant increases in cortisol, but blunted its decrease half-way into the workout. Against that background and in view of the fact that all three doses of caffeine increased the testosterone response to the workout (+15% increase in testosterone in the 200mg and 400mg group and an additional +21% in the 800mg group), the "small" amount of 200mg still appears to be the most prudent (and sustainable!) way to promote fatty acid oxidation (as shown in the study at hand) and exercise performance (by avoiding the potentially ergolytic drop in cortisol levels during the workouts). That the temporary increase in testosterone levels around workouts is not worth a penny, is something you, as an educated SuppVersity reader should be aware of, anyhow (if not re-read the Intermittent Thoughts on Building Muscle series, please)

If we assume that none, or at least only insignificant amounts of the other bioactive components of the coffee got lost during the decaffeination process, this is yet another clear-cut evidence that at least some of the discrepancies between various studies on the potential benefits and down-sides of coffee consumption could simply be attributed to the fact that many of the coffee-skeptics base their arguments on caffeine-only studies. A recent study from Horticulture and Food Research Institute of New Zealand, in which the researchers used a caffeine and diterpenoid rich Colombian coffee extract as a means to attenuated impairment in glucose tolerance, hypertension, cardiovascular remodeling, and nonalcoholic fatty liver disease without changing abdominal obesity and dyslipidemia in a rodent model of metabolic syndrome (Panchal. 2012), does yet prove that there are scientists who appreciate the value of complex natural nutrient matrices and start to exploit the value of (in the broadest sense) medicinal effects of whole foods instead of trying to isolate their allegedly "effective" ingredients.