Antioxidants in coffee may block cancer progression

Coffee packed an unexpected “perk” among patients with mostly metastatic colorectal cancer (CRC): drinking coffee significantly prolonged overall survival (OS) in a large group of CRC patients and the more coffee patients drank, the greater the benefit, a phase III, randomized controlled trial found.

After a median follow up of 5.4 years (Interquartile Range (IQR), 3.2-6.3 years), drinking coffee in the 3 months prior to study enrolment reduced the risk of disease progression and death, with each one-cup per day increase in coffee consumption leading to a 5% lower risk of disease progression at a Hazard Ratio (HR) of 0.95 (95% CI, 0.91-1.00; P=0.04) and a 7% lower risk of death at a HR of 0.93 (95% CI, 0.89-0.98; P=0.004), Christopher Mackintosh, MLA, Phoenix, Arizona, and colleagues reported in JAMA Oncology.

Median OS was 36% longer at 39 months, with a HR of 0.64 (95% CI, 0.46-0.87), for patients who consumed at least 4 cups of caffeinated coffee a day compared with 31 months for those who did not drink coffee (P=0.01), researchers added.

Similarly, progression-free survival (PFS) was 22% longer at a HR of 0.78 (95% CI, 0.59-1.05) for patients who consumed 4 or more cups of coffee a day compared with non-coffee drinkers, they noted.

“[C]offee’s anticancer effects may be related to biologically active constituents of coffee that have been shown to have antioxidant, anti-inflammatory, and antiangiogenic effects,” Mackintosh and colleagues observed.

“T]his is the first…study, to our knowledge, to show a protective effect of coffee consumption in patients with advanced or metastatic CRC [although f]urther research is needed to elucidate the specific mechanism driving these associations,” they acknowledged.

CALGB Trial

A total of 1171 patients with advanced or metastatic CRC were included in this particular analysis. Patients had previously been enrolled in the Cancer and Leukemia Group B (CALGB) which was designed to determine whether cetuximab (Erbitux, Eli Lilly) or bevacizumab (Avastin, Roche) was the optimal biologic to be used together with a concurrent standard chemotherapy backbone.

“Patients were required to have had no previous treatment for advanced or metastatic disease,” the authors pointed out, “[and p]atients who consented completed a diet and lifestyle survey within the first month of enrollment,” they noted.

Patients were asked to describe their usual consumption habits of either caffeinated or decaffeinated coffee and total caffeinated coffee intake was categorized as never or less than 1 cup a day; 2 to 3 cups a day, or 4 or more cups a day. Decaffeinated coffee intake was categorized as never or less than 1 cup a day or 1 cup a day or 2 or more cups a day.

Almost 98% of patients in the current analysis had metastatic CRC, as the authors pointed out.

Compared to those who never drank coffee, OS was 18% longer at a HR of 0.82 (95% CI, 0.67-1.00) among patients who drank 2 to 3 cups of coffee a day.

“Higher total coffee intake was also associated with improved PFS,” researchers noted, PFS again being 18% longer at a HR of 0.82 (95% CI, 0.68-0.99) for patients who drank 2 to 3 cups of coffee a day compared with non-coffee drinkers and 22% longer at a HR of 0.78 (95% CI, 0.59-1.05) for those who drank at least 4 cups of coffee a day.

Outcomes were also largely improved whether patients drank caffeinated or decaffeinated coffee, researchers continued.

For coffee drinkers who consumed at least 2 cups of decaffeinated coffee a day, OS was 36% longer at a HR of 0.64 (95% CI, 0.43-0.95; P=0.002) compared with those who never drank coffee while PFS was 25% longer at a HR of 0.75 (95% CI, 0.52-1.09; P=0.05).

It is noteworthy that OS was extended to an identical extent among those who drank at least 2 cups of decaffeinated coffee a day and those who drank at least 4 cups of caffeinated coffee a day.

Interestingly, although OS was significantly improved among those who drank at least 4 cups of caffeinated coffee a day, no significant association was seen between consumption of caffeinated coffee and PFS at a HR of 0.85 (95% CI, 0.62-1.17; P=0.15).

The authors also noted that the association between increasing coffee consumption and a longer PFS interval was stronger in female than in male patients as was the association between improved OS in patients with a body mass index of less than 25 compared to those with a BMI of at least 25, they added.

As the authors pointed out, a recent analysis of the UK Biobank study also found an inverse association between coffee consumption and all-cause mortality in the general population and this association held true for all types of coffee including instant, ground and decaffeinated coffee.

These findings suggest that noncaffeine constituents of coffee may play a role in this inverse association, as investigators suggested. As the authors themselves pointed out, coffee is actually the largest source of dietary antioxidants in the United States.

“Studies have implicated high oxidative stress in CRC development and metastases,” investigators observed.

“As such, a greater consumption of antioxidants could potentially slow the development of such cancers,” they suggested.

Commenting on the study, Erikka Loftfield, PhD, National Cancer Institute, Rockville, Maryland and colleagues— and the lead author of the UK Biobank analysis—pointed out that although coffee consumption has been reported to improve survival in patients with stage III CRC, “Mackintosh et al are the first to extend this observation to metastatic disease,” they observed. The editorialists also suggested that the potential link between coffee drinking and outcomes in CRC patients is “biologically plausible.”

“Coffee contains more than a thousand chemical compounds and many, including caffeine, chlorogenic acid, and cafestol have known bioactive activity with antioxidant and anti-inflammatory potential,” they pointed out. Furthermore, a cup of coffee tends to increase gut motility which in turn decreases the transit time carcinogens may linger in the gut.

The same compounds in coffee may also favorably interact with gut microbiota.

“Given the lack of evidence that coffee is harmful and, on the contrary, the mounting evidence that it may be beneficial, coffee is a seemingly good candidate for testing its health effects in randomized clinical trials,” as the editorialists suggested.

And, while they acknowledged that randomized clinical trials of coffee drinking are challenging to carry out for a number of reasons, “incorporating coffee drinking into treatment strategies for patients with CRC has practical appeal [although] such recommendations require further research,” they said.

Limitations to the analysis include the fact that most study participants who consumed coffee while being treated for cancer probably consumed coffee before being diagnosed with cancer so that findings don’t allow the authors to tease out whether coffee consumption acts directly on active tumors or whether coffee drinkers develop less aggressive tumors than non-coffee drinkers.

  1. Each one-cup per day increase in coffee consumption led to a 5% lower risk of disease progression and a 7% lower risk of death in patients with mostly metastatic colorectal cancer compared to patients who never drank coffee.

  2. Significant associations between overall survival and progression-free survival were seen with both caffeinated and decaffeinated coffee consumption, suggesting that noncaffeine constituents such as antioxidants in coffee may slow disease progression in advanced CRC.

Pam Harrison, Contributing Writer, BreakingMED™

Macintosh had no conflicts of interest to disclose but many of his co-investigators did which are listed in the publication.

The editorialists had no conflicts of interest to disclose.

Cat ID: 23

Topic ID: 78,23,730,16,23,192,925