Drinking any amount of alcohol likely increases the risk of dementia, suggests the largest combined observational and genetic study to date, published online in BMJ Evidence Based Medicine.

Even light drinking -- generally thought to be protective, based on observational studies -- is unlikely to lower the risk, which rises in tandem with the quantity of alcohol consumed, the research indicates.

Current thinking suggests that there might be an 'optimal dose' of alcohol for brain health, but most of these studies have focused on older people and/or didn't differentiate between former and lifelong non-drinkers, complicating efforts to infer causality, note the researchers.

To try and circumnavigate these issues and strengthen the evidence base, the researchers drew on observational data and genetic methods (Mendelian randomization) from two large biological databanks for the entire 'dose' range of alcohol consumption.

These were the US Million Veteran Program (MVP), which includes people of European, African, and Latin American ancestry, and the UK Biobank (UKB), which includes people of predominantly European ancestry.

Participants who were aged 56-72 at baseline, were monitored from recruitment until their first dementia diagnosis, death, or the date of last follow-up (December 2019 for MVP and January 2022 for UKB), whichever came first. The average monitoring period was 4 years for the US group, and 12 for the UK group.

Alcohol consumption was derived from questionnaire responses -- over 90% of participants said they drank alcohol -- and the Alcohol Use Disorders Identification Test (AUDIT-C) clinical screening tool. This screens for hazardous drinking patterns, including the frequency of binge drinking (6 or more drinks at a time).

In all, 559,559 participants from both groups were included in observational analyses, 14,540 of whom developed dementia of any type during the monitoring period:10,564 in the US group; and 3976 in the UK group. And 48,034 died: 28,738 in the US group and 19,296 in the UK group.

Observational analyses revealed U-shaped associations between alcohol and dementia risk: compared with light drinkers (fewer than 7 drinks a week) a 41% higher risk was observed among non-drinkers and heavy drinkers consuming 40 or more drinks a week, rising to a 51% higher risk among those who were alcohol dependent.

Mendelian randomization genetic analyses drew on key data from multiple large individual genome-wide association studies (GWAS) of dementia, involving a total of 2.4 million participants to ascertain lifetime (rather than current) genetically predicted risks.

Mendelian randomization leverages genetic data, minimizing the impact of other potentially influential factors, to estimate causal effects: genomic risk for a trait (in this case, alcohol consumption) essentially stands in for the trait itself.

Three genetic measures related to alcohol use were used as different exposures, to study the impact on dementia risk of alcohol quantity, as well as problematic and dependent drinking.

These exposures were: self-reported weekly drinks (641 independent genetic variants); problematic 'risky' drinking (80 genetic variants); and alcohol dependency (66 genetic variants).

Higher genetic risk for all 3 exposure levels was associated with an increased risk of dementia, with a linear increase in dementia risk the higher the alcohol consumption.

For example, an extra 1-3 drinks a week was associated with a 15% higher risk. And a doubling in the genetic risk of alcohol dependency was associated with a 16% increase in dementia risk.

But no U-shaped association was found between alcohol intake and dementia, and no protective effects of low levels of alcohol intake were observed. Instead, dementia risk steadily increased with more genetically predicted drinking.

What's more, those who went on to develop dementia typically drank less over time in the years preceding their diagnosis, suggesting that reverse causation -- whereby early cognitive decline leads to reduced alcohol consumption -- underlies the supposed protective effects of alcohol found in previous observational studies, say the researchers.

They acknowledge that a principal limitation of their findings is that the strongest statistical associations were found in people of European ancestry, because of the numbers of participants of this ethnic heritage studied. Mendelian randomisation also relies on assumptions that can't be verified, they add.

Nevertheless, they suggest that their findings "challenge the notion that low levels of alcohol are neuroprotective."

And they conclude: "Our study findings support a detrimental effect of all types of alcohol consumption on dementia risk, with no evidence supporting the previously suggested protective effect of moderate drinking.

"The pattern of reduced alcohol use before dementia diagnosis observed in our study underscores the complexity of inferring causality from observational data, especially in aging populations.

"Our findings highlight the importance of considering reverse causation and residual confounding in studies of alcohol and dementia, and they suggest that reducing alcohol consumption may be an important strategy for dementia prevention."

Read more …Think light drinking protects your brain? Think again

Date:
Source:
The Lancet
Summary:
The STEP UP trials revealed that a 7.2 mg dose of semaglutide led to greater weight loss than the currently approved 2.4 mg dose. Nearly half of participants lost 20% or more of their body weight, while also improving metabolic health. Side effects were mostly mild and temporary. Researchers say this could reshape obesity treatment if confirmed in longer-term studies.

FULL STORY


High-Dose Semaglutide Redefines Weight Loss
A higher semaglutide dose could revolutionize obesity treatment with bigger weight loss and lasting health benefits. Credit: Shutterstock

A higher weekly dose of semaglutide (7.2 mg) can significantly improve weight loss and related health outcomes in adults living with obesity, including those with type 2 diabetes (T2D), according to the results of two large-scale, international phase 3 clinical trials. The findings, published in The Lancet Diabetes & Endocrinology journal, suggest that a higher dose of semaglutide offers a promising new option for people with obesity, including those with T2D, who have not achieved sufficient weight loss with existing treatments.

The STEP UP and STEP UP T2D clinical trials are the first to investigate whether increasing the dose of semaglutide from the currently approved dose of 2·4 mg to 7·2 mg is safe and leads to additional weight reduction. Trial participants were randomized to receive either the higher 7·2 mg dose of semaglutide, the currently approved 2.4 mg dose, or placebo over 72 weeks. All participants -- regardless of treatment group -- received lifestyle interventions such as dietary counseling and increased physical activity recommendations.

In adults without diabetes, a 7·2 mg dose of semaglutide led to an average weight loss of nearly 19%, surpassing the 16% loss seen with 2·4 mg and 4% with placebo. Nearly half of the participants on the higher dose lost 20% or more of their body weight, with about one-third losing at least 25%. Participants also experienced improvements in waist circumference, blood pressure, blood sugar, and cholesterol levels, all key factors in reducing obesity-related health risks. Similarly, in adults with obesity and T2D, the 7·2 mg dose resulted in an average 13% weight loss compared to 10% with 2.4 mg and 3.9% with placebo, along with significant reductions in blood sugar levels and waist size.

Both trials reported that the higher dose of semaglutide was safe and generally well tolerated. Gastrointestinal side effects like nausea and diarrhea, and some sensory symptoms like tingling, were the most common. However, most side effects were manageable, resolved over time, and did not lead to participants dropping out of the trial. No increase in serious adverse events or severe hypoglycemia was observed with the higher dose.

By delivering greater weight reduction and metabolic benefits while maintaining a favorable safety profile, the authors say this higher dose could help more people reach their health goals and reduce the burden of obesity-related complications worldwide. However, they highlight that further research is needed to fully understand the long-term benefits and risks.


Story Source:

Materials provided by The Lancet. Note: Content may be edited for style and length.


Journal Reference:

  1. Sean Wharton, Paula Freitas, Jøran Hjelmesæth, Maria Kabisch, Kristian Kandler, Ildiko Lingvay, Maria Quiroga, Julio Rosenstock, W Timothy Garvey. Once-weekly semaglutide 7·2 mg in adults with obesity (STEP UP): a randomised, controlled, phase 3b trial. The Lancet Diabetes, 2025; DOI: 10.1016/S2213-8587(25)00226-8[1]

Cite This Page:

The Lancet. "This new semaglutide dose helped nearly half of patients lose 20% body weight." ScienceDaily. ScienceDaily, 4 October 2025. <www.sciencedaily.com/releases/2025/10/251004092913.htm>.

The Lancet. (2025, October 4). This new semaglutide dose helped nearly half of patients lose 20% body weight. ScienceDaily. Retrieved October 4, 2025 from www.sciencedaily.com/releases/2025/10/251004092913.htm

The Lancet. "This new semaglutide dose helped nearly half of patients lose 20% body weight." ScienceDaily. www.sciencedaily.com/releases/2025/10/251004092913.htm (accessed October 4, 2025).

RELATED STORIES


Semaglutide Melts Fat—but May Quietly Strip Away Your Strength[2]

July 15, 2025 — Semaglutide, a popular anti-obesity drug, may come with a hidden cost: significant muscle loss, especially in women and older adults. A small study found that up to 40% of weight loss from ...

Hormone Therapy Supercharges Tirzepatide, Unleashing Major Weight Loss After Menopause[3]

July 13, 2025 — Postmenopausal women struggling with weight loss may find a powerful solution by combining the diabetes drug tirzepatide with menopause hormone therapy. A Mayo Clinic study revealed that this dual ...

Weight Loss Linked to Nerve Cells in the Brain[4]

May 27, 2025 — Scientists at the University of Gothenburg have pinpointed a group of nerve cells in the brain stem that appear to be responsible for semaglutide’s appetite- and weight-controlling powers—without ...

Semaglutide Treats Liver Disease in Two Thirds of Patients[5]

Apr. 30, 2025 — A groundbreaking international trial has found that semaglutide, a drug best known for treating diabetes and obesity, can also reverse a dangerous liver disease called MASH in nearly two-thirds of ...

Semaglutide Reduced Cardiovascular Events by 20% in Certain Adults[6]

Nov. 13, 2023 — Semaglutide reduced cardiovascular events by 20% in adults with overweight or obesity and established cardiovascular disease who do not have diabetes, according to new research.   Semaglutide is ...

Scientists Claim That Overeating Is Not the Primary Cause of Obesity[7]

Sep. 13, 2021 — A perspective article challenges the 'energy balance model,' which says weight gain occurs because individuals consume more energy than they expend. According to the authors, ...

TRENDING AT SCITECHDAILY.com[8]


Incredible Images Show Antibiotics Shattering Deadly Bacteria’s Armor[9]

The Nearest Alien Civilization Could Be 33,000 Light-Years Away[10]

Earth May Not Be So Special After All, New Study Finds[11]

Ultra-Processed Food Addiction Is Surging in Middle Age Adults[12]

Read more …This new semaglutide dose helped nearly half of patients lose 20% body weight

A key switch for cellular energy balance has been discovered in cells: it could potentially become the target of new therapies for diseases ranging from Parkinson's to rare disorders caused by defects in the cell's powerhouses, the mitochondria. The switch is called phosphatase B55 (PP2A-B55alpha) and regulates the balance of mitochondria. Experts from Università Cattolica, Rome campus, and Roma Tre Universty have observed that, by reducing its activity, it's possible to attenuate the motor symptoms of Parkinson's in a preclinical model of the disease.

This is the result of a study published in Science Advances, led by Francesco Cecconi, Full Professor of Biochemistry at the Department of Basic Biotechnological Sciences, Intensive Care and Perioperative Medicine at the Università Cattolica, and conducted by Valentina Cianfanelli, Associate Professor at the Department of Science at Roma Tre University and Principal Investigator of the Young Researchers Project at the Gynecological Oncology Unit of Fondazione Policlinico Universitario Agostino Gemelli IRCCS.

Background

Mitochondria are highly complex cellular organelles, vital for cell survival. They are responsible for producing the energy cells need to survive. Their integrity is associated with several diseases, both widespread, such as Parkinson's, and rare, so-called mitochondrial diseases, which can affect various parts of the body, from muscles to eyes to the brain. Inside cells, there is a delicate balance between old or damaged mitochondria that must be eliminated and new ones that must replace them. In some diseases, however, this balance is disrupted, and if mitochondria are lost in excess, or if damaged organelles accumulate in the cell and are regularly not eliminated, the very survival of the cell is endangered.

In the case of Parkinson's disease, for example, the loss of mitochondria also plays a role in the death of dopaminergic neurons that underlies the disease.

The Study

Experts have discovered that B55 plays a key role in regulating mitochondrial homeostasis.

"On the one hand," Professor Cecconi explains, "it promotes the removal of damaged mitochondria by stimulating mitophagy, a selective process for removing inefficient and potentially dangerous organelles. On the other, B55 acts as a controller of mitochondrial biogenesis, stabilizing the main promoter of new mitochondrial formation.

In this way, B55 not only promotes the degradation of damaged mitochondria, but also prevents excessive production of new organelles, thus maintaining a dynamic balance between mitochondrial elimination and synthesis. It is of great interest," the expert emphasizes, "that both these effects depend on the functional interaction between B55 and Parkin, a central protein in mitophagy mechanisms, implicated in Parkinson's disease.

Professor Cecconi and Cianfanelli explain: it is no coincidence that in our research, using animal models of Parkinson's disease (Drosophila, the fruit flies), "we observed that by reducing B55 levels we can improve both the motor defects and the mitochondrial alterations typical of the disease." This effect requires the presence of the Parkin factor and acts primarily on mitochondrial biogenesis.

The idea could be to develop small molecules capable of penetrating the brain and selectively acting on dopaminergic neurons, counteracting their death.

More generally, a 'universal' drug that regulates the action of B55 could be developed for various mitochondrial diseases characterized by mitochondrial loss, including some mitochondrial myopathies and neurodegenerative diseases, Professor Cecconi explains. Furthermore, the deregulation of mitochondrial quality and number also underlies the plasticity of tumor cells and their ability to resist therapies, so controlling B55 could become a promising approach in oncology.

This is why "our future studies will aim to identify safe molecules and therapeutic strategies to modulate B55 in preclinical and human cellular models, especially in order to analyze the effect of its regulation on other neurodegenerative and mitochondrial diseases," they conclude.

Read more …Hidden cellular “power switch” could transform Parkinson’s treatment

More Articles …