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Can You Prevent Your Next Hangover By Using Thrive+?

A single rat study convinced a student majoring in religious studies to start a company and market a hangover solution. The scientific evidence behind the product is of very low quality.

The founder of a company marketing a hangover treatment called Thrive+ had this to say on the show BusinessMakers: “When you click on our ad because you’re interested in it, you get taken to our web page and you say, ‘oh, this is invented at Princeton and a Princeton neuroscience professor helped this with two Princeton professors with PhDs in Biological Engineering on the team’; we have a granted patent on it and did a study.  Once you really start getting into it you go, ‘oh wow, this is really convincing.’”

We will revisit this assertion at the end, as well as the qualifications of the people behind this product, but for now, Thrive+’s website beckons us with its soothing blue background and its lustrous product shots.

Thrive+ is actually a pair of products. The “After-Alcohol Aid” comes in pill form and is meant to reduce the symptoms of short-term alcohol withdrawal as well as to provide your liver with some assistance in metabolizing the drinks you just guzzled. Two to four capsules are said to do the trick. Its complement is a stout tub of “Oral Rehydration Solution”, which promises to be “more effective at rehydrating than even IV bag therapy”. Convinced yet?

Thrive+’s founder calls this product pair “sunscreen for alcohol”, and the central ingredient is a molecule known as dihydromyricetin (DHM).

The Chinese had all the panaceas

Many plants harbour DHM, most importantly Hovenia dulcis.

H. dulcis is also known as the Japanese raisin tree, and it bears mentioning that it has a long history in traditional Chinese medicine as (what else?) a panacea. It’s been used as a treatment for alcohol poisoning (which plays a role in this story), but also as a cure for fevers… and parasitic infections… and spasms. Also, it’s a laxative and it makes you pee a lot. Also, “the stem bark was introduced as a natural drug to treat rectal diseases.” I’m not sure I’d want tree bark “introduced” up there, but it never ceases to amaze me that seemingly every natural product indexed by ancient Chinese healers can take care of all possible symptoms.

The peduncles from H. dulcis have been studied in mice, for example. A study out of China concluded that its juice or vinegar may reduce the negative effects of alcohol on the liver. But because they only used 10 mice per group, it’s hard to conclude much from this experiment. What about DHM itself?

A quick look on Google Scholar shows numerous patents attached to this miraculous chemical: for the treatment of cancer, for promoting sleep, to combat skin ageing, for Alzheimer’s disease.

The problem with the molecule is that it shows poor bioavailability. This characteristic of a drug is a pillar of pharmacology. If you swallow a pill containing 500 mg of a painkiller, but only 10% of these molecules end up in your bloodstream to actually reach their target, the drug is said to have a very low bioavailability. DHM is reported as having “poor structural stability”: indeed, it degrades when exposed to the enzymes produced by your pancreas, to light, and importantly, to pepsin, one of the chief enzymes made by your stomach to digest food. So a pill containing DHM to help your hangover would have to somehow overcome these challenges.

But all this talk about DHM and Japanese raisin trees has not answered a critical question: what exactly is a hangover?

The throbbing headache of hangover science

A hangover rears its head when your blood alcohol level goes back to zero. How bad the hangover is depends on your blood alcohol level at the end of the evening, which itself varies according to time, weight, and sex.

The known contributing causes to a hangover include acetaldehyde, produced as an intermediate step when ethanol is metabolized; dehydration; low blood sugar; and the sleep disturbances resulting in being severely inebriated. Moreover, congeners—substances used to add colour and flavour to a drink—play a role in this cascade of events. Drinks that contain more congeners, like tequila and Bourbon whiskey, produce a stronger malaise the next day.

A comprehensive understanding of what happens inside the body during a hangover is still lacking in 2018, which makes hangovers a perplexing beast. That hasn’t stopped people from coming up with a seemingly inexhaustible list of “hangover cures”, many of which were indexed by Frank M. Paulsen from Wayne State University in the 1960s. This inventory includes juices, vitamins, steam baths, and one of my favourites: “a hot sweat over a live corpse.”

To this list, we can add DHM and Thrive+, and the story of how this product came about raises a number of skeptical red flags.

A rat study gave an epiphany to a religious studies major

Brooks Powell was studying religion as a sophomore at Princeton University when he stumbled upon a scientific paper after a bad hangover. This is the Shen paper, published in the Journal of Neuroscience in 2012. The researchers injected rats with ethanol, or with ethanol and DHM, and looked at their behaviour. They also allowed other rats to voluntarily consume water containing ethanol, or ethanol and DHM. And the results were quite interesting: the injections “counteracted acute alcohol intoxication and also withdrawal signs” and the water laced with DHM “greatly reduced ethanol consumption”. Quite prominently, the authors reported they used 315 rats, which sounds very impressive until you dig into the figures and realize that each experimental group was actually made up of a much smaller subset of this sum, with groups being as small as two rats.

Powell, however, was convinced he had stumbled upon the solution to hangovers (and possibly to alcohol dependency) and showed the paper to his neuroscience professor, eventually recruiting him for his fledgling company which would try to commercialize a product containing DHM and a few other molecules as a hangover cure-all. It may be reassuring that a Princeton University neuroscience professor would act as counsel during the development of this product, but I must point out that Dr. Samuel Wang’s laboratory does not study alcoholism or pharmacology. Rather, his interest lies in motor learning, autism, and optical imaging, with not a single paper published about alcohol metabolism or its effect on the brain.

A visit to Thrive+’s LinkedIn page reveals two of its employees as “integrative medicine” health professionals, which also does not bode well for scientific rigour.

The final product is marketed prominently next to the FDA logo, which may lead you to believe it’s been approved by the Food and Drug Administration; actually, its presence here signifies Thrive+ is being manufactured in a facility that is registered with the FDA, which is not the same thing.

One last question: are there any human studies?

The one human study hasn’t been peer-reviewed

This product has been tested in 19 men and 8 women. I know this, because it’s written in Powell’s patent application for Thrive+.

The result? A 50% decrease in hangover symptoms. However, there was no blinding involved, and no placebo. These volunteers got drunk and reported their feelings the next day. They came back, got drunk again but this time, took Thrive+, knowing what it was, and reported their feelings afterwards. The mere knowledge that this pill should cure your hangover can provoke a significant (though short-lived) placebo response, which this study cannot rule out.

Conclusion

Because the quality of the evidence with regards to Thrive+ and its main ingredient, dihydromyricetin, is so poor, I’m in no position to state with assurance whether the product works or not. Thrive+ is based on a prescientific tradition coupled with under-powered rodent studies and a pretty poor human trial that was never peer reviewed and published. The cost is fairly reasonable but, as far as risks are involved, a neuropharmacologist interviewed about this product voiced an interest in knowing if DHM actually puts a person at greater risk for seizures or convulsions, since its mechanism of action is shared with other drugs that are associated with this risk.

Brooks Powell is not the only one bringing DHM to market as a hangover treatment. Sisun Lee’s company, 82 Labs, has also released a nearly identical product called Morning Recovery, which adds taurine, a stimulant, to the mix.

When Dr. Edzard Ernst, known for his rigorous studies of alternative medicine, took a look at eight hangover cures and the randomized controlled trials they had been put through, he reported that, apart from two encouraging results from solo trials using small sample sizes and unvalidated scoring methods, there was no evidence of effectiveness. His 2005 conclusion still resonates today: “The most effective way to avoid the symptoms of alcohol-induced hangovers is thus to practise abstinence or moderation.”


@CrackedScience

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