Can Probiotics Cure a Hangover?
Probiotics seem to be everywhere these days. They are marketed for numerous health issues, from irritable bowel syndrome and vaginal yeast infections to life-threatening disorders like the bacterial infection Clostridium difficile.
The new probiotic drink is made of genetically engineered bacteria meant to help people feel better the day after drinking.
While the probiotic gummies that you'll find in supermarkets may not do much for you, good clinical evidence does support the C. difficile treatment, known as a fecal transplant, despite a recent setback, and there are always new probiotic regimens entering the scene. One emerging such treatment targets the hangover.
The Lowdown
You read that right – although "hangover" is a loaded term, according to ZBiotics, the company that's developing the product. The popular understanding of a hangover implies a collection of symptoms like a headache and fatigue, many of which result simply from dehydration and low-quality sleep. But those aren't the problems that the new product, a genetically engineered form of a common bacterial species, was developed to confront.
"Dehydration and poor sleep have actually always been pretty simple to deal with by having a good breakfast and some caffeine," notes ZBiotics founder and microbiologist Zack Abbott. Instead, the product targets acetaldehyde, a chemical that accumulates in the body if more than small amounts of alcohol are consumed.
Normally, body cells produce an enzyme that converts acetaldehyde into harmless acetic acid. But the enzyme becomes overwhelmed if you drink more than a little alcohol, or if you have a certain genetic deficiency.
A new probiotic drink aims to neutralize a chemical that builds up in the body after drinking alcohol.
(Zbiotics)
"I started ZBiotics with the hypothesis that if we used edible probiotic bacteria to make enzymes, and chose applications in which the enzymes these microbes make would be useful directly in the gut after you eat them, we could create all sorts of beneficial products," says Abbott. "I started with alcohol with the idea that we can augment the body's natural ability to digest its nasty byproduct, acetaldehyde, helping people feel better the day after drinking."
Next Steps
Based on the premise that the engineered bacteria augments a natural body function, ZBiotics had the product "sampled by thousands of beta-testers," including ZBiotics personnel, with "almost unanimously positive feedback," says Abbott.
"We are working on future scientifically controlled testing for publication."
ZBiotics is to set to launch on the market next week as a probiotic supplement, a category that does not require FDA approval. But some observers are troubled over whether the new product is attempting to serve a medical function without going through the standard drug testing process.
"I am skeptical of any new alternative product that is not FDA approved, has not undergone rigorous double-blind placebo control testing and adverse effects evaluation, and cites anecdotes as evidence of its efficacy," warns Heather Berlin, a cognitive neuroscientist and assistant professor of psychiatry at Icahn School of Medicine at Mount Sinai, in New York.
Abbott acknowledges that his product still needs to undergo rigorous study. "We are working on future scientifically controlled testing for publication," he says, noting that the company was "founded and [is] run by people with backgrounds in academic research."
Open Questions
Moving beyond the need for proper testing, Berlin has an additional concern: will a "hangover"-blocking substance cause people to drink more alcohol, or mask important physiological sensations like thirst?
"If that negative feeling is obscured, they may not [rehydrate], which can cause numerous adverse effects," Berlin says.
As for excessive drinking, there is a treatment on the market that does the opposite of Zbiotics. Disulfiram, commonly given to alcohol abusers, inhibits the very enzyme that ZBiotics supplements, causing acetaldehyde to accumulate especially fast. This makes drinking a pretty miserable experience.
But Abbott says his product would not interfere with disulfiram.
"[Zbiotics] is about enjoying the special moments in life where alcohol happens to be involved, but isn't the main focus."
"Disulfiram globally inhibits the enzyme throughout the entire body, including the liver, creating a massive amount of acetaldehyde at once, making the person ill immediately and forcing them to stop drinking right away," Abbott explains, whereas his product exerts its effects in the gut, and is really only helpful the next day. Thus, timing is everything; the probiotic would not change the experience at the moment of drinking.
"ZBiotics isn't about going out and ripping shots all night," Abbott says. "It's about enjoying the special moments in life where alcohol happens to be involved, but isn't the main focus. Weddings, celebrations, weekends with friends. And wanting to do that enjoyably while being safe and responsible at the same time."
The Cellular Secrets of “Young Blood” Are Starting to Be Unlocked
The quest for an elixir to restore youthful health and vigor is common to most cultures and has prompted much scientific research. About a decade ago, Stanford scientists stitched together the blood circulatory systems of old and young mice in a practice called parabiosis. It seemed to rejuvenate the aged animals and spawned vampirish urban legends of Hollywood luminaries and tech billionaires paying big bucks for healthy young blood to put into their own aging arteries in the hope of reversing or at least forestalling the aging process.
It was “kind of creepy” and also inspiring to Fabrisia Ambrosio, then thousands of miles away and near the start of her own research career into the processes of aging. Her lab is at the University of Pittsburgh but on this cold January morning I am speaking with her via Zoom as she visits with family near her native Sao Paulo, Brazil. A gleaming white high rise condo and a lush tropical jungle split the view behind her, and the summer beach is just a few blocks away.
Ambrosio possesses the joy of a kid on Christmas morning who can't wait to see what’s inside the wrapping. “I’ve always had a love for research, my father was a physicist," she says, but interest in the human body pulled her toward biology as her education progressed in the U.S. and Canada.
Back in Pittsburgh, her lab first extended the work of others in aging by using the simpler process of injecting young blood into the tail vein of old mice and found that the skeletal muscles of the animals “displayed an enhanced capacity to regenerate.” But what was causing this improvement?
When Ambrosio injected old mice with young blood depleted of EVs, the regenerative effect practically disappeared.
The next step was to remove the extracellular vesicles (EVs) from blood. EVs are small particles of cells composed of a membrane and often a cargo inside that lipid envelope. Initially many scientists thought that EVs were simply taking out the garbage that cells no longer needed, but they would learn that one cell's trash could be another cell's treasure.
Metabolites, mRNA, and myriad other signaling molecules inside the EV can function as a complex network by which cells communicate with others both near and far. These cargoes can up and down-regulate gene expression, affecting cell activity and potentially the entire body. EVs are present in humans, the bacteria that live in and on us, even in plants; they likely communicate across all forms of life.
Being inside the EV membrane protects cargo from enzymes and other factors in the blood that can degrade it, says Kenneth Witwer, a researcher at Johns Hopkins University and program chair of the International Society for Extracellular Vesicles. The receptors on the surface of the EV provide clues to the type of cell from which it originated and the cell receptors to which it might later bind and affect.
When Ambrosio injected old mice with young blood depleted of EVs, the regenerative effect practically disappeared; purified EVs alone were enough to do the job. The team also looked at muscle cell gene expression after injections of saline, young blood, and EV-depleted young blood and found significant differences. She believes this means that the major effect of enhanced regenerative capacity was coming from the EVs, though free floating proteins within the blood may also contribute something to the effect.
One such protein, called klotho, is of great interest to researchers studying aging. The name was borrowed from the Fates of Greek mythology, which consists of three sisters; Klotho spins the thread of life that her sisters measure and cut. Ambrosio had earlier shown that supplementing klotho could enhance regenerative capacity in old animals. But as with most proteins, klotho is fragile, rapidly degrading in body fluids, or when frozen and thawed. She suspected that klotho could survive better as cargo enclosed within the membrane of an EV and shielded from degradation.
So she went looking for klotho inside the EVs they had isolated. Advanced imaging technology revealed that young EVs contained abundant levels of klotho mRNAs, but the number of those proteins was much lower in EVs from old mice. Ambrosio wrote in her most recent paper, published in December in Nature Aging. She also found that the stressors associated with aging reduced the communications capacity of EVs in muscle tissue and that could be only partially restored with young blood.
Researchers still don't understand how klotho functions at the cellular level, but they may not need to know that. Perhaps learning how to increase its production, or using synthetic biology to generate more copies of klotho mRNA, or adding cell receptors to better direct EVs to specific aging tissue will be sufficient to reap the anti-aging benefits.
“Very, very preliminary data from our lab has demonstrated that exercise may be altering klotho transcripts within aged extracellular vesicles" for the better Ambrosio teases. But we already know that exercise is good for us; understanding the cellular mechanism behind that isn't likely to provide additional motivation to get up off the couch. Many of us want a prescription, a pill that is easy to take, to slow our aging.
Ambrosio hopes that others will build upon the basic research from her lab, and that pharmaceutical companies will be able to translate and develop it into products that can pass through FDA review and help ameliorate the diseases of aging.
Podcast: Should Scientific Controversies Be Silenced?
The "Making Sense of Science" podcast features interviews with leading medical and scientific experts about the latest developments and the big ethical and societal questions they raise. This monthly podcast is hosted by journalist Kira Peikoff, founding editor of the award-winning science outlet Leaps.org.
The recent Joe Rogan/Spotify backlash over the misinformation presented in his recent episode on the Covid-19 vaccines raises some difficult and important bioethical questions for society: How can people know which experts to trust? What should big tech gatekeepers do about false claims promoted on their platforms? How should the scientific establishment respond to heterodox viewpoints from experts who disagree with the consensus? When is silencing of dissent merited, and when is it problematic? Journalist Kira Peikoff asks infectious disease physician and pandemic scholar Dr. Amesh Adalja to weigh in.
Dr. Amesh Adalja, Senior Scholar, Johns Hopkins Center for Health Security and an infectious disease physician
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Kira Peikoff was the editor-in-chief of Leaps.org from 2017 to 2021. As a journalist, her work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and two young sons. Follow her on Twitter @KiraPeikoff.