Before digging into the results of the summarized study, it’s worth taking a look at what the available research suggests about the health effects of drinking coffee in general.

Large cohort studies and meta-analyses of observational studies from 2012 to 2021 have fairly consistently found that coffee drinking is associated with a lower risk of all-cause mortality and CVD mortality, as well as lower risk of mortality from certain other specific causes, like cirrhosis.^[1]^[2]^[3]^[4]^[5]^[6]^[7]^[8]^[9] Lower risks of cancer mortality have also been reported, but somewhat inconsistently.^[2]^[4]^[5]^[6]^[7]^[8] These risks tend to be lowest in people who drink 2 to 4 cups per day.^[1]^[2]^[3]^[4]^[5]^[6]^[7]^[8]^[9]

One 2019 meta-analysis was designed to more precisely investigate the relationship between coffee and mortality by examining intake in 0.5-cup increments.^[4] Here’s what that study found:

Drinking anywhere from 1.5 to 6 cups of coffee per day was associated with a lower risk of all-cause mortality and CVD mortality.
Drinking 3.5 cups of coffee per day was associated with the lowest risk of all-cause mortality.
Drinking 2.5 cups of coffee per day was associated with the lowest risk of CVD mortality.
Drinking 1 to 2.5 cups of coffee per day was associated with a lower risk of cancer mortality risk, though only by a small amount (3%–4%).

A 2017 umbrella review of meta-analyses on coffee and various health outcomes found that coffee consumption was generally associated with a 17% to 19% lower risk of all-cause and CVD-related mortality.^[9] Consistent with these results, in one of the more recent meta-analyses, the researchers recruited participants from the U.S. and found that CVD mortality risk was lowest (approximately 17%–18% lower) in people who drank 3 to 4 cups of coffee per day.^[5]

One important caveat when interpreting this research is that, unfortunately, many studies do not explicitly define whether a cup of coffee is 8 oz (240 mL), like a cup of water, or 4 oz, the more traditional cup of coffee. The summarized study and the 2015 U.S. dietary guidelines define a cup of coffee as 8 oz. Those same guidelines state that consumption of up to 5 cups per day can be part of a healthy diet.^[7] Conversely, some studies define a cup as much smaller volume, such as 4 oz (120 mL)^[5] and 3.4 oz (100 mL).^[6] In these studies, the risks were lowest at 3 to 4 cups, which would translate into approximately 1.5 to 2 cups if 8 oz is considered the standard.^[5]^[6]

That said, mortality risks tend to be lowest at approximately 1.5 to 4 cups of coffee per day, though there is some variation, and mortality risks do appear to be fairly similar between 1.5 to 6 cups per day.^[4]

One interesting finding in the summarized study was that caffeinated and decaffeinated coffee both showed similarly protective associations. In line with this, the researchers in 5 of 6 studies found that both caffeinated coffee and decaffeinated coffee consumption were associated with lower mortality risks, both to a fairly similar degree.^[2]^[3]^[7]^[4]^[8]^[1] Furthermore, one large cohort study found a lower mortality risk in people who drank brewed coffee (i.e., from grounds) and those who drank instant coffee, though brewed coffee appeared to be associated with a slightly lower risk than instant.^[7]

Equipped with this background, it’s now appropriate to explore the unique finding of the summarized study, that all-day coffee drinking did not show the same protective associations as morning coffee drinking.

Coffee consumption can plausibly increase CVD risk via its caffeine content because caffeine can disrupt sleep and poor sleep has been associated with increased oxidative stress, inflammation, and blood pressure, among other detrimental effects.^[10]^[11] However, this potential detriment only applies to caffeinated coffee, whereas in the summarized study, drinking decaffeinated coffee all day was not associated with a lower risk of CVD. One hypothesis that might explain this phenomenon is that there could be a beneficial effect from the anti-inflammatory compounds that coffee contains, like chlorogenic acid or trigonelline,^[12] and specifically in the morning, when inflammation levels tend to be higher.^[13]^[14] Alternatively, it’s possible that because only 2% of participants drank decaffeinated coffee all day, there just wasn’t enough data to uncover a benefit. As a result, it’s probably too early to rule out whether drinking decaffeinated coffee all day has the same protective associations as drinking coffee in the morning.

Finally, given that a focus of the summarized study was CVD risk, it’s worth exploring some potential contexts in which coffee has been suggested to negatively affect CVD risk. In some studies, including a number of randomized controlled trials, drinking coffee has been reported to increase LDL-C and blood pressure.^[15] Both of these changes would be expected to increase CVD risk. How can these findings be reconciled with the evidence as a whole?

There’s a simple explanation for the connection to LDL-C: coffee can increase LDL-C if it’s made without a filter, such as with a French press (cafetiere). Lipids (e.g., cafestol) that are filtered out of paper-filtered coffee can otherwise increase LDL-C if they are not filtered out.^[16] This is why coffee made with a filter generally does not increase LDL-C. For more detail on the lipid-raising effect of unfiltered coffee, check out this Editor’s Pick from December 2024.

With respect to blood pressure, a 2024 cohort study with a 10-year follow-up period found no differences in blood pressure between coffee drinkers and coffee nondrinkers, regardless of whether blood pressure was measured in home, in a doctor's office, or while ambulatory.^[17] In fact, some research suggests that coffee drinkers have lower blood pressure.^[18] Some research suggests that caffeine can cause an increase in blood pressure in the short term, especially in people who are not habituated to caffeine, but this probably doesn’t reflect the effect of regularly consuming coffee because tolerance is able to develop if caffeine intake isn’t excessive.^[19] Therefore, the evidence does not clearly support a negative effect of regular coffee consumption on blood pressure.

🔍 Digging Deeper: Genetic variability in caffeine metabolism

Genetic factors can play a role in the health effects of caffeine, and by extension, coffee consumption, but what specific effects do they have?

To examine the effects of genetics on caffeine, it’s useful to understand how caffeine is metabolized. There are specific enzymes in the body that metabolize caffeine, and there are several variants of the genes that produce those enzymes. One enzyme, cytochrome P450 1A2, which is responsible for approximately 95% of caffeine metabolism, is coded by the CYP1A2 gene. Different variants of this gene can cause people to be slow, intermediate, or fast metabolizers of caffeine. The current evidence shows that variants in the CYP1A2 gene may influence how much caffeine people habitually consume. This is likely because faster metabolizers need more caffeine to experience the same stimulant effects and, similarly, because slow metabolizers are more prone to experiencing negative side effects from caffeine, such as anxiety.

CYP1A2 gene variants also seem to predict caffeine’s effect on exercise performance, and current evidence indicates that caffeine improves performance in fast and intermediate metabolizers, but not in slow caffeine metabolizers, possibly because the ergogenic metabolites of caffeine (e.g., paraxanthine, theophylline) are generated more readily in faster metabolizers. This phenomenon is explored in detail in this Editor’s Pick from 2023.

It’s also been hypothesized that slower caffeine metabolizers might be at an increased risk of cardiometabolic conditions like hypertension and heart disease if they drink too much coffee.^[20]^[21] However, current evidence from the strongest available research suggests that caffeine-metabolizing gene variants do not influence the effect of coffee consumption on cardiovascular disease risk^[22] or all-cause mortality.^[7]

Does when you drink coffee influence its health benefits? Original paper