Millions of Americans take ginkgo biloba supplements to boost memory and prevent dementia. Studies have never found any solid evidence that ginkgo does any such thing, but it did not seem to be doing much harm.
But last month, scientists released the first government toxicology study of ginkgo biloba, which found that the extract — one of the top-selling herbal supplements in the country — caused cancer in lab animals, including an excessive number of liver and thyroid cancers, as well as nasal tumors.
The findings were somewhat surprising because ginkgo biloba has had a long and apparently benign history of human use. Although it has been associated with bleeding and cerebral hemorrhages in the elderly, there have generally been few reports of serious side effects.
The results of the study do not confirm that ginkgo biloba is dangerous to humans, but it is disturbing that the laboratory animals all tended to suffer the same sorts of injuries, said Cynthia Rider of the National Toxicology Program and the lead scientist of the ginkgo biloba study.
“We often see different targets depending on the sex of the animal or the species, finding one thing here and one thing there,” Dr. Rider said. “But with the ginkgo studies it was consistent across the sexes and the species. The liver was a target, the thyroid was a target, and the nose.”
“That consistency strengthens our conclusions,” she added.
The study concluded that there is clear evidence that ginkgo causes carcinogenic activity in the livers of mice and some evidence linking it to carcinogenic activity in rats’ thyroids.
The mice developed large numbers of multiple liver cancers, including a particularly aggressive type that is rarely seen in the rodents. The number of cancers exceeded the total in the comparison group. In some instances, the number of cancers exceeded the numbers ever seen in mice in the lab, the investigators said.
Officials with the American Herbal Products Association, a trade organization for companies that sell herbs and botanical products, and the American Botanical Council, a nonprofit group that publishes and educates people about medicinal plants, have sharply criticized the study, saying that the ginkgo extract used had a different chemical composition than the extract typically sold in the United States. The government scientists say they purchased it from a major supplier to American supplement companies.
More important, the critics questioned how applicable animal toxicity studies — long considered a mainstay in evaluating cancer risk — are to human health, and how the high doses often used in these studies relate to human consumption.
It is a valid criticism, as doses used in toxicology studies tend to be very high. In the new ginkgo study, mice were given up to 2,000 milligrams of extract per kilogram of body weight, or just over 900 milligrams per pound of body weight, five times a week. Doses sold for human consumption range from 30 to 120 milligrams, regardless of body size.
“This says nothing about toxicity in people, or what would be a safe dose in people,” said Steven Dentali, the trade association’s chief scientific officer. “It’s just a crude tool toxicologists have to determine if something is harmful. If it hurts the animals, maybe it hurts people.”
The Food and Drug Administration already bans ginkgo biloba from food and beverages, and the agency has repeatedly told drink manufacturers to remove ginkgo from its products.
Most recently, F.D.A. officials warned Stewart Brothers, a company in Hood River, Ore., that its juice drinks were “adulterated” with ginkgo, which it called an unsafe and unapproved additive, citing the new report. Several beverage companies, including Rockstar and Just Chill, have removed ginkgo biloba from beverages after receiving letters from the F.D.A.
But when it comes to supplements, the government has a different standard. A substance that is considered unsafe in food items or drinks can be legally sold as a supplement.
“We don’t review supplements before they go to market,” said Tamara Ward, an F.D.A. spokeswoman. “We get involved when there is a risk to the consumer, but manufacturers are responsible for making sure the products do not pose a risk to the consumer and for making sure claims are not misleading.”
The distinction has long rankled consumer advocates. The Center for Science in the Public Interest no longer regards ginkgo biloba as safe and is urging consumers to avoid it.
“The burden now shifts to industry to prove that it is safe,” said Michael F. Jacobson, executive director of the center. “There is no way to do a study in humans. You would need millions of people who take ginkgo biloba and millions who don’t, who all eat the same diet and have the same lifestyle. Government, industry and academia have all generally accepted animal studies as indicators of human risk.”
Moreover, he pointed out, several large clinical trials that followed thousands of elderly people to see if ginkgo biloba delayed cognitive decline failed to find any evidence that the extract was beneficial.
The studies included a large randomized controlled clinical trial of more than 3,000 people aged 75 years and older in the United States and a French study that included 2,820 people over age 70 who were followed for five years.
The F.D.A. is reviewing the new evidence from the toxicology study and could change its guidance in the future, Ms. Ward said.