That fourth cup of coffee is fine. Probably.

The average American consumes about 300 milligrams of caffeine daily—but scientists know surprisingly little about when your next cup of coffee becomes unsafe, James Hamblin reports for The Atlantic.

Caffeine isn't just a morning ritual—it's a drug used for everything from reviving newborns to inducing seizures, Hamblin writes. But research is inconsistent on how many cups of coffee are one too many.

One widely cited daily limit is 400 milligrams, which "comes from sources like [FDA] and the International Food Information Council," according to Hamblin. That's about four eight-ounce cups of coffee, or one Starbucks Venti's worth. But caffeine is one of America's most-consumed drugs; many people drink more than one Venti's worth of coffee daily.

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What's more, not all cups of coffee are created equal in terms of caffeine—some companies are marketing hyper-strong coffee, with names like "Black Insomnia" and "Death Wish." Black Insomnia claims the brew has 702 milligrams of caffeine in a single 12-ounce cup. "That's around five times as much as a home-brew, and three times as much as Starbucks' dark roast," Hamblin writes.

The range of caffeine-infused beverages prompted some researchers to question where the 400 milligram-cap comes from and whether it should be taken seriously.

Esther Myers, a specialist in systematic research reviews at International Life Sciences Institute who has been examining the health effects of caffeine, sought to address that lack of evidence. In the most comprehensive review of caffeine safety to date, Myers looked at 700 studies to identify the most reasonable limit for caffeine consumption.

Myers concluded that the 400-milligram cap is a safe maximum for healthy adults, but pregnant women should stay below 300 milligrams. "Above those levels the team found evidence of links to everything from depression and dysphoria (general unhappiness) to anxiety to hypertension to higher proportions of sperm with DNA damage," Hamblin writes.

However, Myers said the research doesn't mean 500 milligrams of caffeine is unsafe for everyone. "There's a great deal of inter-individual variability in how people respond to caffeine," she explained. "That's one of the research gaps. We need to better identify differences and identify people who are more sensitive."

In fact, according to Hamblin, one of the main takeaways from Myers' research is that we know relatively little about the health effects of caffeine. For instance, the research team noted that more studies are needed on how caffeine affects adults with other health issues, as well as how timing and frequency of caffeine consumption influence its effects.

"The best dose-guidance for now is this broad estimate about what not to do," Hamblin concludes. "For most people, 400 milligrams is almost certainly safe, but not necessarily good" (Hamblin, The Atlantic, 4/26).

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