Pharma & drug development

Turning to turmeric

Turmeric has long been used as a natural remedy, and many studies seem to back that up. However, a recent review has suggested that many of the apparent benefits are bad science. Abi Millar finds out more.

Turmeric has long been thought to have medicinal properties. A popular home remedy in various parts of the world (not least in India, where it is sometimes applied to wounds to speed recovery), it has been credited variously as an antioxidant, an anti-inflammatory, an anti-coagulant and a natural defense against Alzheimer’s disease and various cancers.

Whether or not you believe the internet naturopaths who proclaim it ‘the most powerful herb on the planet’, it wouldn’t be too much of a stretch to suggest this is no ordinary spice. And the evidence seems to go beyond folklore: if you search PubMed for curcumin, turmeric’s most well-known component, you’ll find nearly 10,000 studies referencing the compound. Since 1995, over $150 million in federal funding has been allocated to projects exploring its possible benefits.

Implications in medicine

One study, for instance, found clinical evidence that curcumin might be used as a therapy for mild depression. Another found that curcumin might be more effective in controlling arthritis than arthritis drugs. Still another found the chemical could improve insulin sensitivity, which has implications for diabetes.

However, a widely reported review, published in the Journal of Medicinal Chemistry in January, cast doubt on these findings, claiming that counter to popular belief, curcumin has no demonstrable health benefits.

“To our knowledge, [curcumin] has never been shown to be conclusively effective in a randomized, placebo-controlled clinical trial for any indication,” wrote the authors, who are based at the University of Minnesota, Brigham and Women’s Hospital and the University of Illinois at Chicago.

So does their paper represent a decisive blow for turmeric research, or is the truth more complex than that? And what does this mean for the various research teams intent on turning turmeric into a drug?

A chemical con artist

According to the researchers, there are two big problems with curcumin. The first is that it is a ‘chemical con artist’ – it belongs to a class of molecule known as pan-assay interference compounds (PAINS), which comprise about 5-12% of compounds and often give false readings on drug screening tests.

Curcumin employs a litany of strategies to cloud the test results. For instance, it might interfere with proteins or incandesce under ultraviolet lights. From an outside perspective, these kind of deviant behaviours look just the same as a positive reaction and – if you haven’t ruled out all possible modes of interference – can lead you to see what you want to see.

The other problem is that curcumin is highly unstable and hard to absorb. It reacts with a range of different compounds, and tends to disintegrate under physiological conditions. This makes its hard to determine its bioavailability, although studies have shown that rats absorb less than 1% of the curcumin they eat.

Having picked apart several studies in the field, the authors arrived at a damning conclusion: essentially that the field of turmeric research is rife with misinterpretation. What is more, curcumin lacks any of the characteristics you would typically want in a drug candidate – chemical stability, high water solubility and low toxicity to name a few.

“At first, curcumin appeared to offer great potential for the development of a therapeutic,” wrote the authors. “Unfortunately, no form of curcumin, or its closely related analogues, appears to possess the properties required… The in vitro interference properties of curcumin do, however, offer many traps that can trick unprepared researchers into misinterpreting the results of their investigations.”

Not a panacea

It appears, then, that curcumin is not the panacea that many have hoped. Many media outlets interpreted this finding as an indictment of the spice itself – the headline in Time, for instance, reads ‘Turmeric may not be a miracle spice after all’, while Quartz went for ‘Forget what you’ve heard: Turmeric seems to have zero medicinal properties’.

The researchers, however, have a rather more nuanced message. Lead author Kathryn M Nelson, of the University of Minnesota, points out that we have to differentiate between turmeric and its supposedly active component.

“There’s a lot of evidence that turmeric itself does something good for you – it’s been used in natural remedies for a long time,” she says. “But this focus on this one phytocomopound that’s easily isolated is a mistake, because there’s no evidence from a chemical standpoint that it can do anything for you.”

In short, curcumin is not the active component of turmeric, and any research focusing on curcumin specifically is likely to lead you down a dead end.

“What that active component is may not even be one thing you could distill down – it could be the complex mixture,” says Nelson. “What we suggest is that a more holistic view needs to be taken with turmeric research to find out which parts could be therapeutic.”

Separating science from hype

One promising contender is TAI-LCx, a newly identified component deriving from the essential oils of the root. In 2015, translational biopharmaceutical company Botanisol was awarded a $225,000 grant to explore its potential as an anti-inflammatory. The aim is to create a drug that lacks the health risks of NSAIDs.

“We are looking to develop an anti-inflammatory agent that is safer than currently available treatments,” says David Gang, Washington State University professor and Botanisol chief science officer. “We expect that patients experiencing pain, such as that associated with osteoarthritis, would be able to take an TAI-LCx-based drug much like they do current NSAIDs, either orally or in a cream applied to the skin over the affected area. It will not need to be injected like the biologics are.”

This research builds on a 2010 study, albeit in rats, which found that turmeric essential oils could ease inflammation in the joints. If that finding is replicated in people, it could mean turmeric is useful for arthritis after all – it just won’t be because of the curcumin.

“We have known for a very long time that curcumin is not the most important anti-inflammatory compound in turmeric,” says Gang. “That information is what led to the our work to identify other compounds in turmeric that might be responsible for the potent anti-inflammatory properties of whole turmeric powder. We think we are on track to identify the really important anti-inflammatory agent, or agents, from turmeric, and our results suggest that there might be more than one active compound.”

Evidently, all is not lost for turmeric research. It may not be long until we see the first turmeric-based drug, and it is likely that folk wisdom contains a sizeable grain of truth. In the meantime, however, we need to be careful to separate the science from the hype.

“I think it would be naïve to think there’s one plant that can cure 15 really serious and different maladies,” says Nelson. “There’s a lot of indications for turmeric that people have suggested it could be good for, and it may not be good for all of them – it may be useful for a smaller set of things once we can investigate what the therapeutic components are. People have to be ready for that.

This article appears in the April 2017 edition of Pharma Technology Focus

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