Alcohol Consumption Abundant among animals in Natural World with Molly Gambhir

Drinking is a social activity! 😊 Some animals seem to be able to deal with the effects of alcohol better than humans.

Removing largest serving sizes of wine decreases alcohol consumption, study finds. Really!

Optical illusions or trompe l'oeil for thirsty pub visitors? Let's see how long it will take for paternalistic governments to jump on this excuse!

Perhaps, they should start serving smaller sizes of alcohol in the ivory tower. This may help to reduce the amount of frivolous scientific papers. Just a naughty thought! 😊

For how long will consumers be fooled? Or will it invite some greedy pub owners to exploit it like same price for less booze using the pretext health benefits? 😊

"When pubs, bars and restaurants in England removed their largest size of wine sold by the glass, consumers drank less alcohol"

Removing largest serving sizes of wine decreases alcohol consumption, study finds (article is embargoed until 1/18/2024)

Study shows promise of gene therapy for alcohol use disorder with dramatic results

Good news!

"... The study in nonhuman primates showed that implanting a specific type of molecule that induces cell growth effectively resets the brain’s dopamine reward pathway in animals predisposed to heavy drinking. The gene therapy procedure involves brain surgery, and may be useful in the most severe cases of alcohol use disorder. ...

The implanted virus is not harmful and carries a gene that codes for the protein known as glial-derived neurotrophic factor, or GDNF. It was injected in a specific area of the brain of a group of rhesus macaque monkeys that voluntarily and heavily drink ethanol diluted in water.  After four macaques underwent the procedure, researchers found their consumption dropped by more than 90% compared with a control group. ...

Veterinarians at the ONPRC used magnetic resonance imaging to guide the insertion of GDNF, using an adeno-associated virus in the ventral tegmental area of the brain. The adeno-associated virus is a single-stranded DNA virus that does not cause disease in its subject. The procedure is already used in adult patients with Parkinson’s disease and in children to treat a rare genetic disorder known as aromatic L-amino acid decarboxylase deficiency that, among other symptoms, causes difficulty with movement. ..."

From the abstract:

"Alcohol use disorder (AUD) exacts enormous personal, social and economic costs globally. Return to alcohol use in treatment-seeking patients with AUD is common, engendered by a cycle of repeated abstinence-relapse episodes even with use of currently available pharmacotherapies. Repeated ethanol use induces dopaminergic signaling neuroadaptations in ventral tegmental area (VTA) neurons of the mesolimbic reward pathway, and sustained dysfunction of reward circuitry is associated with return to drinking behavior. We tested this hypothesis by infusing adeno-associated virus serotype 2 vector encoding human glial-derived neurotrophic factor (AAV2-hGDNF), a growth factor that enhances dopaminergic neuron function, into the VTA of four male rhesus monkeys, with another four receiving vehicle, following induction of chronic alcohol drinking. GDNF expression ablated the return to alcohol drinking behavior over a 12-month period of repeated abstinence–alcohol reintroduction challenges. This behavioral change was accompanied by neurophysiological modulations to dopamine signaling in the nucleus accumbens that countered the hypodopaminergic signaling state associated with chronic alcohol use, indicative of a therapeutic modulation of limbic circuits countering the effects of alcohol. These preclinical findings suggest gene therapy targeting relapse prevention may be a potential therapeutic strategy for AUD."

Study shows promise of gene therapy for alcohol use disorder | OHSU News Already used to treat Parkinson’s disease, OHSU researchers found surgical treatment dramatically reduced chronic heavy drinking

GDNF gene therapy for alcohol use disorder in male non-human primates (no public access)

Fig. 2: AAV2-hGDNF delivery to the VTA.

Cheers to no hangovers! This new probiotic could reduce alcohol's negative effects

Good news! I toast to that! 🥂

"... scientists have developed a genetically modified probiotic that accelerates the metabolism of alcohol and safeguards the liver against alcohol-induced harm. The study was carried out on mice and suggests that this breakthrough might one day potentially alleviate hangover symptoms in humans, the researchers said. ...
The findings showed that the treatment reduced alcohol absorption and increased the mice’s alcohol tolerance. ...
Additionally, it reduced the severity and duration of their hangovers. The probiotic also led to lower levels of lipids and triglycerides in the mice’s livers, both of which contribute to alcohol-related liver damage. ..."

From the abstract:

"Alcohol is an essential drug in human life with multiple medical functions, but excessive alcohol intake, even a single episode of binge drinking, can cause serious damage. Reducing alcohol consumption or absorption is a direct way to alleviate the related harm. Alcohol is decomposed successively by alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) in the liver. Here, we produced a human ADH1B (hADH1B)-expressing probiotic, a recombinant Lactococcus lactis, that aimed to enhance alcohol degradation in the intestinal tract after oral administration. Our results showed that the oral hADH1B-expressing probiotic reduced alcohol absorption, prolonged the alcohol tolerance time, and shortened the recovery time after acute alcohol challenge. More importantly, the liver and intestine were protected from acute injury caused by alcohol challenge. Therefore, the engineered probiotic has the potential to protect organ damage from alcohol consumption. Furthermore, this engineered probiotic may have beneficial effects on alcohol-related diseases such as alcoholic fatty liver disease. ..."

Cheers to no hangovers! This new probiotic could reduce alcohol's negative effects

Oral Probiotic Expressing Human Ethanol Dehydrogenase Attenuates Damage Caused by Acute Alcohol Consumption in Mice (open access)

FIG 1 Preparation and characterization of oral recombinant probiotics for treatment of alcoholics.

A hormone shot helps mice sober up

Good news! I toast to that! 😊🍸

"Scientists found that giving mice a shot of a hormone called FGF21, which both mice and humans naturally produce in their livers in response to alcohol, helped mice recover from a drunken stupor, New Scientist reports. ...
But drunk mice that got a shot of FGF21 quickly regained their coordination and sobered up faster than their still inebriated counterparts. Next, the researchers learned that the hormone influenced a group of neurons in the brain that express a chemical neurotransmitter called noradrenaline. ... which could potentially be used to treat alcohol poisoning."

From the highlights and abstract:

"Highlights

• Hormone FGF21 counteracts alcohol-induced loss of consciousness and coordination

• Pharmacologic FGF21 accelerates recovery from alcohol-induced intoxication

• FGF21 exerts its sobering effect by activating the noradrenergic nervous system

Summary

Animals that consume fermenting fruit and nectar are at risk of exposure to ethanol and the detrimental effects of inebriation. In this report, we show that the hormone FGF21, which is strongly induced by ethanol in murine and human liver, stimulates arousal from intoxication without changing ethanol catabolism. Mice lacking FGF21 take longer than wild-type littermates to recover their righting reflex and balance following ethanol exposure. Conversely, pharmacologic FGF21 administration reduces the time needed for mice to recover from ethanol-induced unconsciousness and ataxia. FGF21 did not counteract sedation caused by ketamine, diazepam, or pentobarbital, indicating specificity for ethanol. FGF21 mediates its anti-intoxicant effects by directly activating noradrenergic neurons in the locus coeruleus region, which regulates arousal and alertness. These results suggest that this FGF21 liver-brain pathway evolved to protect against ethanol-induced intoxication and that it might be targeted pharmaceutically for treating acute alcohol poisoning."

A hormone shot helps mice sober up | Science | AAAS

FGF21 counteracts alcohol intoxication by activating the noradrenergic nervous system (open access)

Graphical abstract

Fetal alcohol spectrum disorders: When pregnant women drink alcohol

How serious? How underreported? What about awareness regarding this issue?

How much can male or other partners, friends, and family influence a pregnant woman to drink less, little, or no alcohol during pregnancy?

" ... One recent study found that about 7% of children receiving care for autism or ADHD likely had an undiagnosed FASD.  ..."

"... We do not know exactly how many people have fetal alcohol spectrum disorders (FASDs). Several different approaches have been used to estimate how many persons are living with FASDs in the population. ...
Using medical and other records, CDC studies have identified about 1 infant with FAS for every 1,000 live births in certain areas of the United States. The most recent CDC study analyzed medical and other records and found FAS in 0.3 out of 1,000 children from 7 to 9 years of age. ...
Few estimates for the full range of FASDs are available. ... experts estimate that the full range of FASDs in the United States and some Western European countries might number as high as 1 to 5 per 100 school children (or 1% to 5% of the population). ..."

Data & Statistics on FASDs | CDC

Credits: Johns Hopkins Bloomberg School of Public Health: Global Health NOW

Why younger generations are growing up sober in Western countries

Good news! Quite a contrast to the early 2000s! 

However, the article does not go into whether younger people use other substances instead, e.g. the better and often legalized availability of cannabis in many Western countries.

"Experimenting with alcohol – and drinking to excess – has long been seen as a rite of passage into adulthood, at least in Western cultures. From an early age, often before the legal age, alcohol is embraced as a social lubricant, a way to have fun, make friends and escape day-to-day realities. Few professional or social events are without some form of alcohol.  

But Gen Zers are taking it slow as they enter adulthood, either by not drinking at all, or drinking less often and in less quantity than older generations. The UK’s largest recent study of drinking behaviours showed in 2019, 16-to-25-year-olds were the most likely to be teetotal, with 26% not drinking, compared to the least likely generation (55-to-74-year-olds), 15% of whom didn’t drink. ...
The decline in youth drinking, according to experts, is remarkable and widespread in most high-income European countries, as well as the US, Australia and New Zealand. During lockdown, Gen Z Australians were most likely to have decreased their alcohol consumption, with 44% reporting they were drinking less – more than double the rate for any other generation. Rates of binge drinking among New Zealand’s young people have also dropped by more than half between 2001 and 2012, and have continued to drop since. ...
For example, concern about losing control and developing a drinking addiction is markedly heightened among young people. ...
When researching in the early 2000s, amid an era of heavy alcohol and party drug use, Pennay remembers young people discussing hedonistic abandon and their wish to switch off by “getting obliterated and having a good time”. It’s the opposite now ..."

Why Gen Zers are growing up sober curious - BBC Worklife A complex combination of outside pressures and information overload is driving young people to snub alcohol, far more than generations before them.

Credits: Johns Hopkins Bloomberg School of Public Health: Global Health NOW

Just 4 alcoholic drinks a week could contribute to cognitive decline

Concerning if confirmed! Even regular light and moderate consumption of beer or wine can cause harm according to this study. However, if the study is correct, would the prevalence of cognitive decline in the population be much larger than it actually is.

There are indeed some possible issues with this study: "The main limitations of the study include that χ and T2* can reflect changes in myelin as well as iron, alcohol use was self-reported, and MR estimates can be influenced by genetic pleiotropy."

So don't feel guilty yet drinking your next beer! Cheers!

"... The hypothesis driving the research arose from studies associating high brain iron levels with neurodegenerative diseases such as Alzheimer’s and Parkinson’s. Abnormal accumulations of iron in the brain have been detected in the brains of heavy alcohol drinkers ...
“In the largest study to date, we found drinking greater than seven units of alcohol weekly associated with iron accumulation in the brain,” ...
“Higher brain iron in turn linked to poorer cognitive performance. Iron accumulation could underlie alcohol-related cognitive decline.” ...
One unit of alcohol is defined here as 10 milliliters of pure alcohol. A big glass of wine, for example, could be anywhere from two to three units of alcohol, while a regular can of beer can contain between 1.5 and two units of alcohol. ...
“Alcohol suppresses hepcidin production, the major hormone-regulating iron homeostasis,” the researchers explained. “This suppression increases intestinal absorption of dietary iron and limits export of iron from hepatocytes.” ..."

Just 4 alcoholic drinks a week could contribute to cognitive decline

Associations between moderate alcohol consumption, brain iron, and cognition in UK Biobank participants: Observational and mendelian randomization analyses (open access)

Genes for Alcohol Use Disorder and Alzheimer’s Risk Overlap

Good news!

"... To answer these questions, Kapoor and his team looked at genetic data from about 700,000 families involved in the NIAAA’s Collaborative Studies on the Genetics of Alcoholism (COGA), as well as genetic variants and surveys about drinks per week from the UK Biobank dataset, then compared those to data from analyses of adult and fetal brains that determined how much RNA was transcribed from particular genes, and which genes were epigenetically silenced or expressed.

This multi-omic approach enabled the researchers to map to the level of changes in a single base pair ...
While the study’s meta-analysis of mutations revealed many genes associated with alcohol use, the team zeroed in on two genes associated with high alcohol consumption (measured in drinks per week), SPI1 and MAPT, because previous studies had linked them to neurodegenerative diseases. ..."

"... In this study, we use multi-omics approaches, to fine-map AUD [alcohol used disorder] and DPW [drinks per week] associations at single SNP resolution to demonstrate that rs56030824 on chromosome 11 significantly reduces SPI1 mRNA expression in myeloid cells and lowers risk for AUD and DPW. Our analysis also identifies MAPT as a candidate causal gene specifically associated with DPW. Genes prioritized in this study show overlap with causal genes associated with neurodegenerative disorders. ..."

Genes for Alcohol Use Disorder and Alzheimer’s Risk Overlap: Study | The Scientist Magazine® Genetic, transcriptomic, and epigenetic data reveal molecular mechanisms tying these disorders to each other and to immune disfunction.

Multi-omics integration analysis identifies novel genes for alcoholism with potential overlap with neurodegenerative diseases (open access)