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We’ve talked previously about the health benefits of coffee and the antioxidant compounds responsible for it’s bitterness. To add to the “perks” of coffee consumption, a recent report in the Journal of Cancer Epidemiology Biomarkers & Prevention suggests that caffeine protects against breast cancer in women that have a BRCA1 gene mutation [1].

What is BRCA1? The acronym stands for breast cancer 1, early onset. The BRCA1 gene encodes a protein that plays a role in maintaining genomic stability and acts as a tumor suppressor. Approximately 5%-10% of breast cancer and ovarian cancer is hereditary and 30%-50% of these are due to DNA mutations in the genes BRCA1 and BRCA2 [2]. Women age 35-40 that carry the BRCA1 mutation are particularly susceptible with a risk between 45%-60% of developing breast cancer [2]. The absolute risk of cancer by age 70 is reported to be between 45% and 87% [3-4].

The authors of the report had previously evaluated the association between coffee consumption and the risk of breast cancer among women who had detrimental mutations in either BRCA1 or BRCA2. They observed a statistically significant reduction in the risk of breast cancer among women who consumed six or more cups of coffee per day compared to those who never drank coffee [5]. The association was only observed for BRCA1 and for caffeinated coffee.

Ninety-five percent of caffeine is metabolized in the human body by a member of the cytochrome P450 family of enzymes, CYP1A2, which stands for cytochrome P450, family 1, subfamily A, polypeptide 2. The cytochrome P450 proteins catalyze many reactions involved in drug metabolism and the synthesis of cholesterol, steroids and other lipids. CYP1A2 also metabolizes acetaminophen (Tylenol) and caffeine. Decreased enzyme activation and impaired caffeine metabolism is associated with a common A to C polymorphism in the CYP1A2 gene (meaning a genetic variation in an individual’s DNA sequence, in this case a specific A to C basepair substitution that alters the function of CYP1A2) [6].

In the present study, the authors examined whether the CYP1A2 genotype (meaning a person’s genetic makeup, in this case the difference in the CYP1A2 DNA sequence between individuals) modifies the association between a history of coffee consumption and the risk of breast cancer. A total of 411 BRCA1 mutation carriers (170 cases and 241 controls) and their coffee consumption habits were evaluated. The CYP1A2 genotype did not affect breast cancer risk. However, among women with at least one variant C allele (meaning an alternative DNA coding sequence) in CYP1A2, specifically the CYP1A2*1F allele (an A to C basebair substitution at a specific location in one or both copies of the DNA coding sequence for CYP1A2), those who drank coffee had nearly a 3-fold decrease in the risk of breast cancer compared with women who never drank coffee.

The authors suggest that mechanisms other than induction of CYP1A2 may account for the influence of caffeine on breast cancer risk. Coffee contains a number of biochemically active compounds including caffeine, phytoestrogens (including flavonoids) and other phytonutrients (including tocopherols). However, caffeine is the only major compound in coffee known to be metabolized by CYP1A2. Thus the authors attribute the decrease in breast cancer risk to prolonged caffeine exposure among individuals that are “slow metabolizers”.

Coffee is a major contributor to the total in vitro antioxidant capacity of the diet. An investigation of the quality of vitamin and polyphenolic antioxidants in beverages found that black tea contained the highest concentration of high-quality antioxidants, followed by coffee [7]. Here’s the breakdown:

This may be particularly relevant for women who carry the BRCA1 mutation as a decrease in the expression of genes involved in the antioxidant response has been shown for BRCA1-deficient cells [8].

A separate hospital-based, case-control study done last year evaluating the role of coffee in breast cancer etiology found among premenopausal women that consumption of caffeinated coffee was associated with a decrease in breast cancer risk [9]. The study included 1,932 women with primary, incident breast cancer and 1,895 controls. Women who consumed four or more cups of coffee per day experienced a 40% reduction in breast cancer risk. Although this study didn’t examine individual genetics, it is one of many demonstrating coffee’s protective effects against breast cancer.

It’s fascinating that impairment of caffeine metabolism coupled with high coffee consumption can result in a reduction in breast cancer risk for women who have an otherwise increased risk due to a BRCA1 gene mutation. The BRCA1 variant C allele isn’t common; in their previous study, the authors indicate that >95% of the mutations identified weren’t pathogenic [5]. Nevertheless, these results underscore the importance of addressing individual genetic variability in the metabolism when evaluating diet-disease associations.

References

1. Kotsopoulos et al. The CYP1A2 genotype modifies the association between coffee consumption and breast cancer risk among BRCA1 mutation carriers. Cancer Epidemiol Biomarkers Prev. 2007 May;16(5):912-6. DOI: 10.1158/1055-9965.EPI-06-1074
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2. Ferla et al. Founder mutations in BRCA1 and BRCA2 genes. Ann Oncol. 2007 Jun;18 Suppl 6:vi93-8.
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3. Antoniou et al. Risk models for familial ovarian and breast cancer. Genet Epidemiol. 2000 Feb;18(2):173-90.
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4. Ford et al. Risks of cancer in BRCA1-mutation carriers. Breast Cancer Linkage Consortium. Lancet. 1994 Mar 19;343(8899):692-5.
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5. Nkondjock et al. Coffee consumption and breast cancer risk among BRCA1 and BRCA2 mutation carriers. Int J Cancer. 2006 Jan 1;118(1):103-7.
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6. Sachse et al. Functional significance of a C–>A polymorphism in intron 1 of the cytochrome P450 CYP1A2 gene tested with caffeine. Br J Clin Pharmacol. 1999 Apr;47(4):445-9.
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7. Vinson et al. Vitamins and especially flavonoids in common beverages are powerful in vitro antioxidants which enrich lower density lipoproteins and increase their oxidative resistance after ex vivo spiking in human plasma. J Agric Food Chem. 1999 Jul;47(7):2502-4.
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8. Bae et al. BRCA1 induces antioxidant gene expression and resistance to oxidative stress. Cancer Res. 2004 Nov 1;64(21):7893-909.
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9. Baker et al. Associations between black tea and coffee consumption and risk of lung cancer among current and former smokers. Nutr Cancer. 2005;52(1):15-21.
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I love my coffee. Who doesn’t want (or need for all you coffee addicts out there) a cup of freshly brewed java to start their day? However, the bitterness of coffee is something most of us could do without.

Now chemists in Germany and the U.S. say they have identified the chemicals that are largely responsible for coffee’s bitterness. Their study, one of the most detailed chemical analyses of coffee bitterness to date, was presented this week at the 234th national meeting of the American Chemical Society [1].

Contrary to popular belief, only 15% of coffee’s perceived bitterness is due to caffeine [1]. In fact, coffee is a complex mixture of chemicals and an estimated 25 to 30 compounds have been thought to contribute to coffee’s bitter taste. Surprisingly, however, the chemists found that coffee’s bitterness is due to two main classes of compounds produced during the roasting process; chlorogenic acid lactones and phenylindanes. Both compounds are antioxidants and are not present in green, unroasted coffee beans.

During roasting, chlorogenic acid, a polyphenol in raw beans, is converted to chlorogenic acid lactones. Further roasting results in the breakdown of the lactones to phenylindanes. The lactones are responsible for the mild bitterness of light- to medium-roasted coffee, while the second breakdown product, phenylindanes, produce the harsh, bitter taste of dark-roasted coffee.

Chlorogenic acid lactones have been known for some time to be produced by the roasting process [2], but their role as a source of bitterness was not known until now. Perhaps more importantly, the identification of phenylindanes adds to the growing body of knowledge investigating the health benefits of coffee.

What you say? Health benefits?

Indeed, coffee consumption offers a number of potential health benefits. The results of epidemiological research suggest that moderate coffee consumption may help prevent type 2 diabetes mellitus [3-4], Parkinson’s disease [5] and liver disease [6]. Although coffee consumption has not been found to be associated with significantly increased cardiovascular disease risk, it is associated with increases in several cardiovascular disease risk factors, namely blood pressure [7] and plasma homocysteine [8]. Some individuals may be more vulnerable to the adverse effects of caffeine in coffee, including people with hypertension, children, adolescents and the elderly. Nevertheless, habitual intake of caffeinated beverages may prevent heart disease in the elderly.

It’s been suggested that this research on coffee bitterness will lead to a “better cup of joe”. However, I wouldn’t be too surprised if the the compounds that give coffee its bitter taste also turn out to be responsible for coffee’s health benefits.

Have any tips for a great cup of coffee? I’d love to hear them!

References

1. Battling Bitter Coffee: Chemists Identify Roasting As The Main Culprit. ScienceDaily 2007 Aug 22.
2. Farah et al. Effect of roasting on the formation of chlorogenic acid lactones in coffee. J Agric Food Chem. 2005 Mar 9;53(5):1505-13.
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3. Salazar-Martinez et al. Coffee consumption and risk for type 2 diabetes mellitus. Ann Intern Med. 2004 Jan 6;140(1):1-8.
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4. van Dam and Hu. Coffee consumption and risk of type 2 diabetes: a systematic review. JAMA. 2005 Jul 6;294(1):97-104.
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5. Ascherio et al. Prospective study of caffeine consumption and risk of Parkinson’s disease in men and women. Ann Neurol. 2001 Jul;50(1):56-63.
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6. Ruhl and Everhart. Coffee and tea consumption are associated with a lower incidence of chronic liver disease in the United States. Gastroenterology. 2005 Dec;129(6):1928-36.
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7. Noordzij et al. Blood pressure response to chronic intake of coffee and caffeine: a meta-analysis of randomized controlled trials. J Hypertens. 2005 May;23(5):921-8.
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8. Olthof et al. Consumption of high doses of chlorogenic acid, present in coffee, or of black tea increases plasma total homocysteine concentrations in humans. Am J Clin Nutr. 2001 Mar;73(3):532-8.
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In February 2007, researchers at Appalachian State University announced the results of a clinical study on the flavonoid quercetin at the Southeastern Regional Meeting of the American College of Sports Medicine, held in Charlotte, N.C. Their results showed that quercetin may help reduce illness and maintain mental performance in physcially stressed test subjects. I’ve written about the antioxidant quercetin in a previous article as an alternative to dichloroacetate (DCA), a chemotherapeutic agent that was recently shown to selectively inhibit cancer cell growth in lung, breast and brain tumor cells grown in culture and lung tumors grown in immunocompromisted rats.

In December 2005, the Defense Advanced Research Projects Agency (DARPA) awarded Appalachian State University 1.1 million to fund a two-year study of the effects of quercetin [1]. DARPA is seeking ways to maintain troop immune systems during times of physical and cognitive stress. Dr. David Nieman is the principal investigator of the study and a professor in the Department of Health, Leisure and Exercise Science at Appalachian State University. He has been investigating the influence of exercise and nutrition on the immmune system for the last 23 years.

The double-blind, randomized, placebo-controlled study provided 1,000 mg/day of high-purity quercetin, a polyphenol, plus niacin and vitamin C to aid in absorption, to 20 trained cyclists for five weeks. A second group of 20 cyclists received a placebo. Three weeks into the study, participants rode a bicycle to the point of exhaustion three hours per day for three days. Blood and tissue samples were collected and analyzed to track any physicological changes that occurred.

Only 5% of the group that received quercetin reported illness after being physically stressed, compared with 45% of the participants who received placebo. No adverse side effects were observed. Surprisingly, the immune-boosting properties of quercetin weren’t readily observable until after the three-day intense exercise period. Additionally, when given an alertness test, those participants that were given quercetin better maintained their ability to react after exhaustion.

Said Dr. Nieman [2]:

It appears that it takes significant stress to bring out quercetin’s infection-fighting properties. This all happened when athletes were under high oxidative stress, when stress hormones were high, and they were also undergoing muscle damage.

Nieman plans a follow-up study to see if quercetin has any benefits for people who are undergoing everyday mental stress.

More about quercetin can be found in these posts:

• Quercetin
• Alternative to Dichloroacetate

References

1. Defense Dept Funds $1.1 Million for Research. The College of Fine & Applied Arts, Appalicain State University. 2005 Dec 7.
2. Research at Appalachian State Indicates Natural Plant Substance Helps Reduce Illness in Physically Stressed Athletes; Findings May Have Military Application. Appalachian State University News. 2007 Feb 8.
3. Sampson et al. Flavonol and flavone intakes in US health professionals. J Am Diet Assoc. 2002 Oct;102(10):1414-20.
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