Could turmeric supplements cause liver injury in some people?

Seven of the 10 individuals identified as having liver injury following turmeric supplementation carried a specific human leukocyte antigen (HLA) allele, known as HLA-B*35:01, despite this normally existing in the population at a frequency of about 6-7%. HLA alleles are genes that code proteins that help the immune system recognize cells as either part of the body or as foreign objects, meaning they play a role in immunity or autoimmunity.

Hoofnagle said they could not say with certainty that all of the cases they discovered were due to turmeric, as many of the people they identified with liver injury were taking other drugs at the time. There did appear to be a particular risk for people with the HLA allele HLA-B*35:01, which needs further investigation.

“So, of our 10 cases, we could be wrong about several of them. So, it may be that this allele is absolutely necessary. We don’t know that when we look at the cases that had the allele and compare it to the three that didn’t, the cases with the allele had this classic, look, you see, whereas the ones that didn’t have the allele, they were a little bit different,” Hoofnagle said.

He and other authors are currently looking at conducting further research to better understand this allele and the mechanisms underpinning the heightened risk of liver injury they had observed.

One of the reasons why liver injury occurs in certain individuals could be that curcumin is a phenolic compound, which makes it a bioactive compound in the human body.

Previously, research has shown that people carrying this genetic variant were more likely to experience liver injury after using Polygonum multiflorum, an herb native to China and used in traditional Chinese medicine.

Hoofnagle explained that the use of green tea supplements, mostly in the form of weight loss supplements, had also been linked to liver injury.

“These other herbals that have been implicated also have phenols. So it’s beginning to kind of come together that something about phenols affects [carriers of] B*35:01 and makes it react in the liver,” he said.

Kristin Kirkpatrick, MS, registered dietician and a dietician at Cleveland Clinic told Medical News Today that it was important to consider the bigger picture when analyzing this data, and consider the other factors that can influence liver health:

“This study examined not only turmeric in a supplemental form but also the addition of piperine, which appeared to enhance bioavailability. The liver is the body’s TSA agent. You can’t move forward in the body without first being screened by this gatekeeper. Supplements make their first stop there, and therefore, the liver takes the brunt of the energy the body takes to break down, detoxify, and allow in or remove.”
— Kristin Kirkpatrick, MS

“In regards to liver injury, it’s estimated that potentially 1 in 3 individuals now have metabolic dysfunction-associated steatotic liver disease (MASLD) and the further along the disease is, the harder for the liver to do its job well. If it can’t detoxify efficiently, it’s more likely to experience injury,” Kirkpatrick said.

Hoofnagle said treating turmeric supplements as though they are as safe as turmeric used in food, which the majority of regulation since the 1970s has done, was a mistake. While acknowledging that turmeric has been used in Indian medicine for thousands of years, he pointed out this was mainly for digestive issues and that there was a difference between using some spice in a meal and taking a whole gram in a capsule every day.

“It’s a typical Western approach to traditional medicines. You try to find out what’s the active principle, and then the more the better, right? The higher the dose, the better. Well, that’s not true in biology. In biology, the correct dose is the correct dose. And if you go higher, all you have is more side effects,” he explained.

He said that this created regulation complications, as the FDA does not regulate herbal medicines.

“What I’m saying is, no, we’re not talking about a traditional medicine. We’re talking about a purified component that’s given in far higher doses. That’s a medicine. So I know it’s posed as an herb, but I would say, no, it’s a medicine. …[T]hat’s my attitude, that once you start messing with traditional medicines, you’re not dealing with them anymore […] when you start chemically modifying or extracting things, it’s not really a traditional medicine anymore,” he said.