Ethanol at the Crossroads

I. Ethanol: A Deuterium Depleted Nutrient?

My husband, winemaker Kristof Nils Anderson, and I own a small wine brand in Napa Valley. We hand-farm two, one-acre Cabernet Sauvignon plots without herbicide or pesticide use. I became acquainted with the research of Dr. Stephanie Seneff PhD, a Senior Research Scientist at the MIT Computer Science and Artificial Intelligence Laboratory, many years ago as a young mother reading about health and nutrition for my family. (Dr. Seneff wrote about sulfur deficiency in Wise Traditions for the Weston A. Price Foundation.)

My husband became an early supporter of The Monarch Challenge, advocating for “clean farming” in Napa and Sonoma vineyards. Dr. Seneff’s research, including Toxic Legacy, her book on the detrimental health and environmental effects of glyphosate, is foundational to ongoing advocacy for clean farming in the wine industry.

In early 2026, I wrote a speculative essay, “A New Way of Thinking About Wine: Wine and the Fourth Phase of Water,” in which I suggested that wine’s “matrix” might include the role ethanol plays in creating exclusion zone water, demonstrated to have health benefits. Because I cited a paper by Dr. Seneff on the critical role of sulfate in maintaining exclusion zone water, I forwarded my essay to her.

Much to my surprise, given how deeply immersed in research she is, she graciously read my essay and responded with her own fascinating, controversial argument for why organic wine consumed in moderation might benefit one’s health: she suspected that ethanol produced by microbes during fermentation is a valuable deuterium-depleted nutrient, and she shared the paper under review that supports this claim.

Like sugar, she said, ethanol is an excellent energy source because it can be converted to acetyl-CoA in just two enzymatic steps, both involving dehydrogenases, and each yielding one molecule of NADH, a carrier of deupleted protons. Should I wish to write an essay expanding on her idea, she said, she’d happily check it to make sure I got the science right. I accepted her challenge, and this essay is the result.

Endogenous Ethanol

Recent public health guidelines frame alcohol as a Group 1 carcinogen with no safe level of consumption (Anderson, et al., 2023). Data shows a doubling of alcohol-attributed cancer deaths in a three-decade period (1990-2023) (Chinmay, et al., 2026) despite per capita ethanol consumption rising only slightly, from 2.45 to 2.48 gallons of pure ethanol per person (Slater, et al., 2025). One wonders if some other factor is augmenting this detrimental outcome. (As it turns out, the data is not exactly as advertised.) (Frank, 2026.)

Far more interesting data, to me, concerns non-alcoholic fatty liver disease (NAFLD), the most common type of chronic liver disease worldwide and leading cause of liver transplants. Despite a 124.6% increase in cases of NAFLD from 1990-2021, and global prevalence of one in four people, the World Health Organization has not classified NAFLD as a priority non-communicable disease (Tang, et al., 2025). One can’t help wondering what is driving the surge in liver disease that is not caused by alcohol.

As the general population increasingly struggles with metabolic health (O’Hearn, et al., 2022 ), many readily accept the viewpoint that there is no safe amount of alcohol, quick to banish the important role that wine and beer have played in human culture and health since the birth of civilization. According to the 2025 Gallup poll (Saad, L., 2025), 54% of Americans polled say they drink alcohol on occasion, the lowest percentage since 1939, and 53% of those polled believe moderate drinking (one to two drinks a day) is bad for one’s health.

Many winemakers, who directly observe the natural power of fermentation, including its ability to preserve nutrients and make them more bioavailable, are disinclined to dismiss ethanol as an evolutionary misstep. The alcohol dehydrogenase (ADH) genes that code for enzymes involved in ethanol metabolism originated more than 400 million years ago, long before the first hominids stumbled upon overripe, fermenting fruits. (About 10-21 million years ago hominids developed a genetic mutation in the ADH4 enzyme allowing them to metabolize ethanol.) (Goldman, et al., 2025)

Ethanol is not foreign to human physiology; microbes living synergistically in the human gut produce small amounts of endogenous ethanol amounting to blood alcohol concentrations of 0.01–0.08 mg/dL (Sosa, 2023) that is readily converted into energy for the mitochondria (Chandel, 2021).

Just for kicks, I propose a more nuanced and controversial view of ethanol: that it is not inherently a poison, and the human body may, in fact, have evolved methods of using ethanol as a cellular nutrient. To some, this may seem like a matter of semantics, as there is a critical distinction between the small amount (3-4 grams a day) of endogenous ethanol a healthy body produces and a larger volume of beverage alcohol that can overwhelm metabolic pathways: 14 grams of ethanol in a standard alcohol drink in the United States (Stamation, 2025).

Driving my speculation is a new preprint, “Do Methylation Pathways Carry Microbially Derived Deuterium-Depleted Methyl Groups to Support Mitochondrial Heath? A Novel Hypthothesis,” (Seneff, et al., 2026) that suggests endogenous ethanol can act as a nutrient in an ancient biological partnership between humans and our gut microbiomes that is also a masterful defense system at the atomic level. To understand the elegance of this system, it’s necessary to look through the lens of deutenomics, the study of how the heavy hydrogen isotope deuterium (²H), impacts cell biology.

Deuterium: Bull in the Mitochondrial China Shop

It has been more than a few years since my last biology class, and I was an English major, so a refresher on quantum biology is in order (at least for me). Inside each cell, mitochondria transform nutrients from food into ATP, the energy cells can use, through a process called oxidative phosphorylation.

Mitochondria have two membranes. Nutrient derivatives—such as pyruvate, fatty acids, and acetate derived from ethanol—cross into the innermost compartment, known as the matrix. The citric acid cycle oxidizes carbon from these fuels after their conversion to acetyl-CoA, stripping away high-energy, negatively charged electrons.

Electrons then move along the inner membrane’s transport chain, pumping protons (positively charged hydrogen ions, H⁺) out into the space between the mitochondrion’s two membranes, creating an electrochemical gradient (Scitable).

Here’s where things really get wild: protons naturally want to flow back into the matrix and mainly do so by passing through an enzyme called ATP synthase that functions like a biological nanomotor spinning thousands of times per minute (Sommer, et al., 2008) The spinning nanomotor’s energy converts ADP into ATP, while complex IV of the electron transport chain separately reduces oxygen to create mitochondrial water (Ahmed, et al., 2023).

Everything in this loop works beautifully until deuterium (²H), an ungainly hydrogen isotope twice as heavy as protium (¹H) that contains both a proton and a neutron, tries to enter the mitochondrial matrix by passing through the delicate ATP synthase nanomotor. Dr. Seneff and colleagues propose that deuterium, with its extra neutron baggage and twice the atomic weight of light hydrogen, could muck things up royally, disrupting ATP synthase and causing oxidative stress by causing the nanomotors to stutter (Seneff, et al., 2025). In the literature of deutenomics, deuterium is often compared to a bowling ball hitting a delicate nanomotor.

Prior to reading Dr. Seneff’s work, I knew vaguely of deuterium from the movies. Deuterium is used to make “heavy water” (D₂O), which Nazi Germany wanted during World War II to use as a neutron moderator in building a nuclear weapon. The only commercial producer of heavy water was the Vemork hydroelectric plant in Norway. Norwegian resistance fighters sabotaged a ferry carrying steel drums of heavy water to Germany so that it sank in a fjord, therefore obstructing Germany’s race to create a nuclear bomb before the United States (Lobell, 2018).

Deuterium (atomic symbol D or ²H) is an isotope of hydrogen found naturally in sea water and in the human body at a blood serum concentration six times that of calcium (Seneff, et al., 2025). Today, heavy water is still used as a neutron moderator in nuclear reactors, in nuclear fusion research, to create solvents for nuclear magnetic resonance spectroscopy, and in biomedical tracing.

Whatever wisps of intrigue clung to deuterium in my memory from matinees with popcorn dissipated as I read more about its negative effect on cellular energy production. Deuterium homeostasis is the concept of keeping the body’s deuterium below an ideal threshold for metabolic health.  Experimental studies show that depleting deuterium in drinking water is correlated with inhibited cancer growth, improved brain and mood function, and metabolic health (Seneff, et al., 2025).

The Elegant Solution to Heavy Hydrogen: Microbially Derived Protons

Naturally, the human body has adapted numerous ways to keep deuterium out of mitochondria, since the heavy isotope sabotages energy production. One of these methods, proposed in the novel hypothesis by Seneff, Nigh, and Kryiakopoulos (Seneff, et al., 2026) involves microbially produced ethanol in the human gut.

The preprint mentions microbially derived ethanol in the context of the overlooked but crucial role the gut microbiome plays in providing deuterium-depleted, one-carbon units to the methylation pathways. The paper examines in depth the methylation and demethylation processes that deliver protons to the mitochondria, protecting ATP synthase nanomotors from damage by deuterium (Seneff, et al., 2026).

It proposes that beneficial microbes in the human gut break down fiber and produce hydrogen (¹H) that has lost 80% of the deuterium levels normally found in water. This “deupleted” hydrogen is reduced into metabolites such as ethanol, acetate, and butyrate. According to the paper, these microbially produced nutrients “are likely to be low deuterium nutrients, and, for this reason, all are likely vital for the health of the mitochondria in the host.” (Seneff, et al., 2026)

Endogenous ethanol, in this context, would not be a toxic metabolite but rather a nutrient contributing isotopically depleted hydrogen to metabolism. By outsourcing fermentation to beneficial microbes, the human body secures a continuous internal source of lightweight hydrogen.

The hydrogen molecules that later become part of NADH, the coenzyme that delivers electrons to the mitochondrial electron transport chain, are largely free of the heavy hydrogen (²H). Microbial ethanol production can be viewed as an evolutionary means of keeping deuterium out of the delicate ATP synthase nanomotors and out of water in the mitochondrial matrix.

Ethanol is metabolized into acetate in two steps: alcohol dehydrogenase (ADH) turns ethanol into acetaldehyde, and acetaldehyde dehydrogenase (ALDH2) turns acetaldehyde into acetate (Goldman, et al., 2025). The two reactions involved in ethanol metabolism yield two molecules of NADH, carriers of deuterium-depleted protons (Seneff, et al., 2026), and one molecule of acetate, which is easily converted into acetyl-Coenzyme A in the matrix, powering the citric acid cycle (Seneff, 2026).

Acetate can contribute carbon to the synthesis of butyrate, the favorite food of the colonocytes in the gut epithelium. This low-deuterium butyrate functions as both nutrient and shield, reinforcing the structural stitches of the blood-brain and intestinal barriers and suppressing local cellular inflammation (Seneff, et al., 2026).

Ethanol has long been viewed as a waste product, but it also serves as fuel in the mitochondria of yeast cells, especially under oxidative stress during fermentation. In another paper co-authored by Dr. Seneff, “Cancer, Deuterium, and Gut Microbes: A Novel Perspective,” (Seneff, et al., 2025) we see that fermenting, budding yeast cells convert glucose to ethanol, release it into the substrate, and later take it up again to fuel the citric acid cycle in their own mitochondria. Here, too, ethanol functions as a nutrient.

When yeast enzymes construct an ethanol molecule, they prefer pulling light hydrogen atoms from their surroundings because C-H and O-H bonds are easier to break than C-D and O-D bonds (containing deuterium). (Seneff, et al., 2026) This is known as the kinetic isotope effect. As a result, fermentation can lower the ratio of deuterium to protium in ethanol, depending on sugar, water, and fermentation conditions.

There’s only one small problem: yeast’s extensive isotopic fractionation may leave ethanol lower in deuterium than standard water, but wine, beer, and liquor are not considered low-deuterium foods; they contain both water and ethanol, and deuterium content has to be assessed separately (Lech, et al., 2025). Sensitive SNIF-NMR can measure naturally occurring deuterium isotope ratios in purified wine ethanol, to determine the geographical origin and water source of wine grapes and detect whether sugar or was added after fermentation (Viskic, et al., 2021).

Did I mention one small problem? Here’s another: As Dr. Seneff’s hypothesis points out, ethanol is broken down into deuterium-depleted fuel in the mitochondria by acetaldehyde dehydrogenase, but the toxic intermediary step acetaldehyde must be cleared first: “acetaldehyde is highly reactive, so ethanol is not an ideal nutrient for this reason (Seneff, et al., 2026).” Well, shoot. One can never have one’s cake and eat it too, I suppose.

And yet, some studies demonstrate that moderate consumption of alcohol has a positive effect on the output of microbially-derived nutrients generally. As a fascinating recent paper on alcohol and the gut microbiome (Melamed, et al., 2025) explains, “Moderate alcohol intake has been shown to alter gut microbial composition by increasing Bifidobacterium and A. muciniphila, while enhancing overall microbial diversity. It may also contribute to the production of gut-derived microbial anti-inflammatory metabolites, particularly SCFAs such as acetate, propionate, and butyrate.” (More about this later.)

Moderate alcohol consumption may also encourage production of polyunsaturated fatty acids (PUFAs). As the paper explains, both short chain fatty acids and polyunsaturated fatty acids can cross the gut barrier and mitigate inflammation, providing a positive connection between moderate alcohol consumption, the gut microbiome, and good health. Whatever the effects of moderate drinking may be, they are part of complex interrelationships, many of which remain entangled and poorly understood.

II. Why No One Seems Able to Hold Their Liquor Anymore

Too Much of a Good Thing: The NADH Bottleneck

The more I read about ethanol metabolism, the more paradoxical I find it, and that’s what makes it interesting. (Most accounts of ethanol metabolism are not interested in these paradoxes, preferring to focus on its status as a poison.) Consider this: ethanol is an excellent energy source, almost too good, because in both brain and liver, ethanol metabolism is prioritized over other carbon sources (Goldman et al., 2025).

The necessity of clearing the toxic intermediary, acetaldehyde, from cells is often pointed to as the reason that ethanol gets preferential treatment, temporarily shutting down the metabolism of fats, proteins, and carbohydrates. I’m not so sure.  It’s more like something signaled to the metabolism that Thanksgiving and Christmas just arrived, all rolled into one.

Imagine someone in a perfect state of health drinking an alcoholic beverage for the first time. Let’s say it’s Eve, in the Garden of Eden; the Serpent tempts her with a gin martini. She tastes it. It’s good.

In her body, ADH oxidizes ethanol to acetaldehyde, reducing one molecule of NAD+, an empty shuttle bus capable of picking up electrons and protons, into one molecule of NADH, a full shuttle bus ready to deliver high-energy electrons to the electron transport chain in the mitochondria (Goldman, et al., 2025).

Acetaldehyde is then oxidized into acetate by ALDH2, creating another NADH molecule full of high-energy electrons. The acetate is transported to tissues, where it can be converted into acetyl-CoA, the universal two-carbon entry molecule for cellular respiration, or even into butyrate, a short-chain fatty acid. There is a catch, though; unlike glycolysis, which can create a small amount of quick energy without oxygen, ethanol fuel depends on functional mitochondria and a steady oxygen supply (Goldman, et al., 2025).

Ethanol is a highly reduced molecule with many carbon-hydrogen bonds (C₂H₆O) and a dense repository of mobile electrons. In fact, in a direct-ethanol fuel cell or enzymatic fuel cell, the oxidation of ethanol by enzymes creates high-energy electrons that are stored in NADH; these can be electrochemically stripped off, causing the electrons to flow through a circuit to generate power (Ali, et al., 2022).

Freeing four electrons in two metabolic steps rapidly changes the NADH/NAD+ ratio, so that ethanol oxidation pauses the metabolism of fuels like fatty acids and glucose to use up the NADH reserve (Goldman, et al., 2025). In one study, an ethanol dose high enough to create a BAC of 0.08% in 30 minutes was given intravenously to participants who were studied over the course of four hours. In this six-person study, ethanol decreased total-body fat oxidation by 79%, protein oxidation by 39%, and almost completely halted the increase in carbohydrate oxidation normally seen after glucose infusion (Shelmet, et al., 1998).

If Eve stops with one martini, the NADH bottleneck will be short-lived; but let’s say the Serpent tempts Eve with a pitcher of martinis. The NADH bottleneck becomes gridlock, like a parking lot filled with so many honking Waymos full of passengers that no one can get in or out. The citric acid cycle stalls.

Ethanol clearance is not regulated in the same way glucose is, though it is constrained by enzyme activity, NAD+ availability, and mitochondrial NADH reoxidation. Once the cascade starts, thermodynamics pushes it forward, yielding NADH until the supply is cleared (Cederbaum, 2012). Imagine manning a food booth at a school carnival.  The soft serve machine gets stuck in the ON position, and you can’t turn it off. You begin filling cones and giving them away, as fast as you can. (This actually happened to me once.) It’s how I imagine ethanol metabolism.

Because of the gridlock, fatty acid synthesis accelerates, as the liver uses acetyl groups to form triglycerides. A person in this state may develop hypoglycemia, particularly if glycogen stores are low, and the high level of circulating acetate will inhibit the burning of stored fat. Mitochondrial stress generates reactive oxygen species that damage cellular proteins, lipids, and DNA. Acetaldehyde floods the cells and contributes to alcohol-related harm (Cederbaum, 2012).

The nasty, hungover feeling Eve will experience after drinking excessive amounts of beverage alcohol has multiple possible contributors (Mackus, et al., 2020). (Don’t do it, Eve!) This destructive wave of acetaldehyde is what most accounts of ethanol metabolism love to linger on. If you want to win any debate about ethanol, all you need to learn is one big word: acetaldehyde.

Much to my surprise, a medicinal chemist thought to slow acetaldehyde formation during heavy drinking by replacing hydrogen in alcohol with deuterium! He claimed that drinking a large cocktail made with his deuterated ethanol, called Ethanol-D, caused fewer unpleasant symptoms than a similar cocktail made with regular ethanol (Bettenhausen, 2021). (It was also quite expensive!) I suppose this is an example of picking one’s poison.

In Zurich, Switzerland, researchers developed an edible nanotech gel that they envision as a product consumed alongside alcohol, that causes a cascade of enzymatic reactions in the stomach, bypassing the liver, and converting ethanol to acetic acid without the intermediary acetaldehyde (ETH Zurich, 2024). Would you drink this? I wouldn’t. But it does suggest an interesting rabbit trail, investigating the interactions of ethanol and nanotech.

A person with a healthy metabolism may be able to handle occasional overindulgence, but a person with poor gut health and metabolic problems, whose citric acid cycle is already sluggish (for instance, one in four people with NAFLD), may be highly alcohol-intolerant. Ethanol metabolism looks like a toxin problem, but maybe it’s more of an energy problem. This helps explain the confounding disconnect I sometimes experience when talking to people about wine, which I view as part of a healthy diet in moderation.

Glyphosate, Gut Dysbiosis, and Ethanol Metabolism

Recall Dr. Seneff’s hypothesis that the gut microbiome is the crucial yet overlooked source of deuterium-depleted nutrients for mitochondria. Dr. Seneff refers to the microbiome as “an atomic sieve, ideally positioned near the entry point in the body for deuterium-containing food and water (Seneff, et al., 2025).” Bacterial enzymes, through the kinetic isotope effect, “prune” light hydrogen and shuttle it to the mitochondrial matrix. The deuterons that are left behind are captured by gut bacteria, attached to organic molecules, and excreted, thus maintaining a state of deuterium homeostasis (Seneff, et al., 2025).

Anyone who finds this hypothesis dubious might consider what happens in gut dysbiosis, when beneficial microbes have been wiped out by antimicrobials. Production of deuterium-depleted nutrients like acetate and butyrate, which microbes make through hydrogen gas recycling, stalls. The insufficient supply of butyrate stresses the colon cells, perhaps allowing deuterium into the mitochondrial intermembrane space and causing oxidative stress (Seneff, et al., 2025.) At the same time, endogenous ethanol production by opportunistic microbes ramps up!

In extreme cases of gut dysbiosis, a rare condition called auto-brewery syndrome can occur, in which a person’s own gut produces enough ethanol to intoxicate them. Excess endogenous alcohol production from microbial overgrowth has been tied to metabolic disease, including non-alcohol-associated fatty liver disease (NAFLD). In one study, participants with advanced liver disease had the highest endogenous blood alcohol concentration, which could be lowered experimentally with a round of broad-spectrum antibiotics (Goldman, et al., 2025).

Gut dysbiosis has become commonplace in modern life due to multiple factors, including environmental toxins like microplastics and heavy metals, antibiotics, modern diet, and I believe most of all, the widespread use of glyphosate in industrial agriculture. (Just walk into any Target and look at the rows of probiotic pills in candy-colored plastic bottles. Probiotics have become trendy.)

Glyphosate was deemed safe for humans because it works by inhibiting the EPSP synthase enzyme, paralyzing the shikimate pathway in plants (Seneff, 2022); its manufacturers apparently did not consider that this powerful antimicrobial also wipes out beneficial microbes in the human gut.

Gut dysbiosis caused by glyphosate, I believe, is a primary underlying factor in the negative health outcomes linked to moderate drinking, as well as NAFLD. In a new preprint, “Is Atherosclerosis Induced by Defective Methylation Pathways? A Role for Lipid Peroxidation in Protecting Mitochondria from Deuterium Overload,” (Seneff, 2026), Dr. Seneff proposes that gut dysbiosis underlies multiple pathologies linked to mitochondrial dysfunction, including the formation of plaques in the artery walls that sequester deuterium.

Dr. Seneff’s deutenomics framework turns the traditional model of inflammation upside down. In her model, the massive inflammatory response to pathogenic overgrowth is not just an attack mechanism, but also an emergency biophysical reclamation project designed to generate deuterium-depleted protons for the mitochondria when the gut’s primary proton-filtering system fails (Seneff, et al., 2026).

In an unbalanced gut microbiome, opportunistic bacteria like Clostridium and Salmonella multiply, flooding the intestines with hydrogen sulfide gas that is toxic to beneficial microbes. With the source of deupleted protons gone, host cells face ATP starvation and deuterium contamination. Immune cells such as neutrophils and macrophages respond to control the pathogens, upregulating the enzyme NADPH oxidase, which generates reactive oxygen species. NOX2 produces superoxide, which is converted to hydrogen peroxide (H₂O₂) by superoxide dismutase (Seneff, et al., 2026).

Dr. Seneff hypothesizes that this workaround provides a new source of quantum proton tunneling. The hydrogen peroxide can be detoxified through catalase or peroxidase reactions, producing two molecules of deuterium-depleted matrix water. This allows the ATP synthase nanomotors to run smoothly, despite the severe cellular damage in the gut caused by oxidative stress (Seneff, et al., 2026).

While a link between gut dysbiosis and liver disease is well-established, I don’t think anyone has considered it through the lens of Dr. Seneff’s work on deuterium overload. In a dysfunctional microbiome, endogenous ethanol production increases at the same time that ALDH2 enzymes crucial to ethanol metabolism degrade, leaving the body unable to clear highly reactive acetaldehyde. Hydrogen peroxide violently suppresses ALDH2’s mitochondrial clearance of acetaldehyde. What happens then?

ALDH2 is highly sensitive to oxidative stress. Hydrogen peroxide depletes mitochondrial glutathione and triggers lipid peroxidation. Reactive aldehydes directly bind to and inactivate ALDH2. According to Dr. Seneff, “ALDH2 deficiency impairs cellular energy by causing toxic aldehyde accumulation. This buildup damages the electron transport chain, reduces ATP synthesis, and creates oxidative stress, leading to decreased mitochondrial respiration, abnormal calcium handing, and mitochondrial structural damage (Seneff, 2026).”

Because oxidative stress shuts down normal mitochondrial oxidation of ethanol, the burden shifts to the peroxisomes and the enzyme catalase, which, in the presence of hydrogen peroxide, turns from a passive antioxidant into an active metabolic engine. Catalase uses the immune-derived hydrogen peroxide to oxidize endogenous ethanol into acetaldehyde right inside the peroxisome. Dr. Seneff hypothesizes that this reaction generates deuterium-depleted metabolic water inside the cell (Seneff, et al., 2026).

However, because mitochondrial ALDH2 has been inhibited, the cell still has no efficient way to turn the acetaldehyde into benign acetate. Accumulating acetaldehyde damages proteins, tears apart the gut barrier, and forces tissue to find an emergency workaround for the backlog of acetaldehyde. In this case, parallel non-oxidative ethanol metabolism produces additional metabolites but fails to clear the acetaldehyde (Goldman, et al., 2025).

Less than 1% of ethanol goes through non-oxidative metabolism in the liver and brain. Resulting metabolites, fatty acid ethyl esters (FAEEs), build up in the liver and pancreas; new studies propose that FAEEs, rather than acetaldehyde, contribute substantially to alcohol-induced liver injury (Goldman, et al., 2025.)

In cases of gut dysbiosis, the cell may shunt deuterated acetyl groups into fatty acid synthesis rather than into the citric acid cycle, locking heavy deuterium atoms into carbon backbones safely apart from the mitochondrial matrix. Further research is needed to explore the impact of FAEEs in the brain (Goldman, et al., 2025). Non-oxidative metabolism of ethanol is glossed over in most discussions of ethanol toxicity, but I find it particularly interesting; FAEE deposits in brain, heart, and liver tissue correlate most strongly with alcoholic disease.

I can only speculate whether these dangerous metabolites might be an emergency effort to sequester excess deuterium, much as arterial plaques are proposed deuterium traps in Dr. Seneff’s paper. If so, trading the oxidative toxicity of the catalase/acetaldehyde pathway for the membrane-stiffening deposits of fatty ethyl esters would be a drastic fallback.

Akkermansia Muciniphila: The Extraordinary Story of an Anti-Obesity Gut Microbe, Deuterium Depletion, and Red Wine Polyphenols

The gut microbe Akkermansia muciniphila is having a moment; maybe you’ve seen an Academy Award winning actress talking about A. muciniphila supplements for weight management on social media. The gut microbiome is well known to influence the endocrine and immune systems and to regulate appetite by stimulating the release of hormones like GLP-1 (which pharmaceuticals like Ozempic or Wegovy try to mimic).

In particular, A. muciniphila has been linked to reduced body mass, improved glucose tolerance, higher levels of anti-inflammatory macrophages, increased expression of cells coding for GLP-1 secretion, and greater GLP-1 concentration in the plasma. This invaluable microbe has an inverse relationship to metabolic disease, yet an estimated 18% of Americans have no detectable amounts of A. muciniphila in their gut microbiome (Zhou, et al., 2020).

The bioactive molecule involved in stimulating GLP-1 secretion was not known until the publication of the paper, “Akkermansia Muciniphila Secretes a Glucagon-Like Peptide-1-Inducing Protein That Improves Glucose Homeostasis and Ameliorates Metabolic Disease in Mice” (Yoon, et al., 2021). Researchers filtered the fluids surrounding the bacteria and found that A. muciniphila secretes a specific protein called P9 that interacts with enteroendocrine cells and triggers the beneficial metabolic hormone GLP-1 (Yoon, et al., 2021).

They tested their findings by giving pure P9 protein to mice eating a high-fat diet. The improvements in blood sugar, fat burning and weight control were dramatic. (Yoon, et al., 2021). There is yet another good reason you want A. muciniphila in your life: Dr. Seneff hypothesizes that A. muciniphila produce acetate and propionate that cross-feed other butyrate-producing bacteria in the microbiome, ultimately yielding deuterium-depleted nutrients to the colonocytes (Seneff, et al., 2025).

The primary food of A. muciniphila is the sulfomucin layer produced by goblet cells in the intestines. (“Muciniphila” means “mucus-loving,” so it’s important to suspend one’s capacity to be grossed out.) Sulfomucins are highly-sulfated forms of mucus that are resistant to bacterial degradation. A. muciniphila possesses specialized sulfatases that allow it to cut the sulfate groups off these sulfomucins in order to consume the underlying sugar backbone (Alarjani, et al., 2026).

A. muciniphila consumes the sulfomucins and converts them into small metabolites that are then fully metabolized by other microbes to produce carbon dioxide and hydrogen gas (that is likely very low in deuterium). Yet other microbes recycle the hydrogen gas into organic nutrients (deuterium-depleted), primarily short-chain fatty acids that are a source of fuel for the goblet cells. The metabolites simultaneously signal to the goblet cells to produce more fresh mucus in a beneficial nutritive cycle. Deuterium is safely packaged as waste into specialized molecules that can trap deuterium, such as histamine and bis-allylic carbon atoms (Seneff, et al., 2025) and excreted from the body in feces, maintaining deuterium homeostasis.

A breakdown of this ecosystem—where goblet cells produce less sulfomucin or A. muciniphila are not available to recycle it into deuterium-depleted short-chain fatty acids—would trigger a leaky gut barrier and mitochondrial dysfunction. Patients with alcohol use disorder (AUD) have an increased number of goblet cells and more active mucus production, paradoxically. Excess alcohol consumption damages the intestinal lining, signaling the gut to drastically ramp up its mucose production as a protective emergency response. Gut stem cells are signaled to create more mucus-secreting goblet cells and fewer nutrient-absorbing cells (Mellis, et al., 2022), which is obviously a disastrous long-term tradeoff.

Interestingly, an overgrowth of A. muciniphila is sometimes seen in connection with diseases such as Parkinson’s Disease (Seneff, et al., 2025) (Chiantera, et al., 2023) and even in cases of glyphosate exposure (Walsh, et al., 2023), combined with a deficiency of other microbes. In overgrowth situations, hydrogen generated when A. muciniphila metabolizes sulfomucin may be used by other microbes to reduce sulfate to hydrogen sulfide instead of converting carbon to acetate (Birg, et al., 2025). This would lead to a toxic microbiome environment; balance in a gut microbiome (and perhaps all things) is ideal.

Because A. muciniphila is an obligate anaerobe that thrives in a zero-oxygen atmosphere, it is highly-sensitive to reactive oxygen species. It has developed an extraordinary relationship with red wine polyphenols like resveratrol and anthocyanins, antioxidants that are able to clear out reactive oxygen species. Red wine polyphenols consistently trigger a significant "bloom" of A. muciniphila in the gut (Kemperman, et al., 2013  ) by creating a dense prebiotic substrate.

The bacteria possess special enzymes that break down complex wine phenols, unlocking metabolites that cells and other bacteria can use for fuel and anti-inflammatory protection (Rodriguez-Daza, et al., 2023 ). This is the most direct connection between moderate red wine consumption and metabolic health I’ve ever come across. Polyphenols also have mild antimicrobial effects, selectively inhibiting sulfur-reducing bacteria and maintaining a balanced microbiome.

Recent studies indicate that polyphenols induce goblet cell differentiation, increase mucus layer thickness, and reduce colitis. However, it remains unclear whether this is directly due to the polyphenols signaling the goblet cells or if A. muciniphila is also involved in signalling (Rodriguez-Daza, et al., 2022.) The beneficial relationship is clear: “Studies show that grape polyphenols stimulate the expression of the Muc2 gene, nudging your goblet cells to secrete a fresher, more robust layer of mucus. By increasing its primary food supply, the polyphenols indirectly build a luxurious ‘all-you-can-eat’ habitat specifically favoring Akkermansia over other bacterial competitors.” (Rodriguez-Daza, et al., 2023 ).

The story of A. muciniphila is an example of a beautifully attuned, complex, interconnected system. The good news is that gut dysbiosis can be reversed and metabolic health regained. Reversal of gut dysbiosis through polyphenol supplementation alone has been documented. Polyphenols are, of course, available in many non-alcoholic forms, such as cranberries, tea, pomegranates, and grapes.

Significantly more polyphenols are extracted during maceration and fermentation of grapes into wine, however. The free resveratrol in wine is 11.44 mg/L compared to 0.15 mg/L in grape juice (Pinheiro, et al., 2025). In one study, ascorbic acid, beta carotene and grape polyphenols were evaluated for their effect on A. muciniphila; only grape polyphenols stimulated the bloom of A. muciniphila. Analysis suggests that it is the poor bioavailability (!) of grape polyphenols that, paradoxically, makes them so beneficial to the bacteria (Van Buiten, et al., 2024).

Experiments in A. muciniphila supplementation are also ongoing, and in cirrhosis patients, the reintroduction of the beneficial bacteria is promising in that it downregulates hepatic fibrotic pathways. In a cirrhotic liver, inflammation and dense collagen deposits prevent mature hepatocytes from proliferating; at the same time, hepatic stem cells remain frozen in a weird kind of limbo, unable to differentiate and regenerate the liver.

A. muciniphila works by repairing the intestinal barrier and reducing the influx of endotoxins. Liver fibrosis has always been considered irreversible, despite the regenerative capacity of a healthy liver, yet these experiments show improvements in fibrosis (Oguri, et al., 2024).  It is interesting to consider how an influx of deuterium-depleted nutrients to the hepatic mitochondria might play a role in this improvement.

Rethinking Ethanol: The Siloed Approach in not Enough

We have considered how glyphosate-driven dysbiosis may destroy the gut microbiome’s ability to create light, deuterium-depleted fuel, impair ALDH2’s detoxification of acetaldehyde from endogenous ethanol, drain protective glutathione reserves, and weaken cell membranes, leaving them susceptible to the solvent properties of ethanol and a chronic inflammatory state. And that’s all before taking a first sip of beverage alcohol!

To add insult to injury, residual glyphosate in non-organic beverage alcohol made from grapes and grains farmed with glyphosate further intensifies the toxic effect of what might otherwise be a health-enhancing beverage in moderation. For a winemaking community that already picks fights when it comes to defining classical winemaking vs. natural winemaking, my argument will ruffle feathers.

And yet I’m suggesting a paradigm shift that should interest all wine drinkers and move the debate beyond winemaking technique and labels to health—of both body and industry. Wine, I’d argue, is a healthy person’s beverage. With fewer than 7% of Americans considered healthy according to cardiometabolic markers, (O’Hearn, et al., 2022 ) a shocking statistic, wine consumption has nowhere to go but down unless the trend reverses. Globally eliminating glyphosate (and ensuring it’s not replaced with something even more toxic) would help reestablish normal metabolic function, including the detoxification pathways needed to metabolize beverage alcohol in moderation.

In this speculative essay, I’ve proposed a nuanced and controversial view of ethanol: that it is not inherently a poison and may, in fact, have evolved as a cellular nutrient. My argument is that ethanol can be both an elegant evolutionary source of ultra-clean fuel and a poison when abused or consumed in large amounts, so its effect on the body is context-dependent.

It is worth examining how and when ethanol works constructively as a nutrient. The systemic toxicity we attribute to alcohol consumption today is enhanced, I believe, by exposure to the modern agrochemical glyphosate, which disrupts the body’s ability to safely clear metabolic intermediates.

Conventional siloed thinking—that all alcohol is poison, or that glyphosate is safe and effective because humans don’t possess a shikimate pathway—has led to an environment where elegant biological systems have been weaponized against us. Connecting quantum biology, environmental toxicology, and the gut-liver-brain axis allows one to appreciate the beauty of human metabolic pathways and to understand why our modern population is so increasingly intolerant of metabolic stressors, including wine, which might otherwise provide health benefits in moderation.

My positive experience as someone who enjoys organic wine in moderation does not negate the negative experiences of those who are alcohol intolerant or those who abuse alcohol or struggle with addiction, and vice versa. Unfortunately, I increasingly meet people who suffer from multiple syndromes who tell me they cannot metabolize alcohol; they are therefore primed to believe the paid, public-health “Buzzkill” propaganda on New York City subway cars stating reductively that “alcohol is a known carcinogen,” rather than considering how gut dysbiosis might paralyze ethanol-detoxification enzymes, create a toxic bottleneck, and upend deuterium homeostasis, inviting cancer. Some take the extreme view that alcohol should be banned. I believe in individual choice, along with complexity, nuance, and continued independent research as part of the discussion.

I am grateful to Dr. Seneff for her generosity in sharing her research, ideas, and speculations with non-scientists like me in her desire to find practical solutions, educate, and heal. I would also like to thank Dr. Seneff for reading this essay and for sharing an article from Nature Microbiology titled, “Akkermansia Muciniphila Secretes a Glucagon-Like Peptide-1-Inducing Protein that Improves Glucose Homeostasis and Ameliorates Metabolic Disease in Mice” and suggesting that I include relevant information in this essay.  Stephanie’s Substack is an excellent source of information about Dr. Seneff’s research, accessible to scientists and non-scientists alike.

This speculative essay was written by Jennifer Anderson, a writer and co-founder of KNA Wines Napa Valley. Jennifer has a BA in English from Wheaton College, an MA in English from University of California at Davis, and she was a Wallace Stegner Fellow at Stanford University from 2001-2003. Her short fiction has appeared in The Best American series.

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“First Off…(Notes From Production)” © 2020-2026. All rights reserved. I did not use generative AI in writing this essay. I did, however, find AI helpful as a search engine and research tool.