Metformin's real power may be in the gut

In continuation of my uodate on metformin 

For decades,physicians and scientists thought metformin, the leading type 2 diabetes medication taken by millions worldwide, mainly targets the liver to suppress glucose production. But a new Northwestern University study in mice has found this "wonder drug" instead focuses primarily on the gut, acting to prevent glucose levels rising in the blood by driving glucose utilization inside cells lining the intestine.

The body relies on glucose as a fast and versatile fuel, but too much glucose can lead to insulin resistance and ultimately damage blood vessels and organs. The study found metformin slows mitochondrial energy production in gut cells, forcing the intestine to metabolize extra sugar.

"Metformin essentially helps the intestine suck the glucose out of the bloodstream, which further highlights that the gut plays a major role in regulating blood sugar levels," said corresponding author Navdeep Chandel, professor of biochemistry and molecular genetics at Northwestern University Feinberg School of Medicine.

The study is published in Nature Metabolism.

The study builds off findings from previous work in Chandel's lab, which found metformin lowers blood sugar by blocking a specific part of the cell's energy-making machinery called mitochondrial complex I, a key enzyme in cellular respiration.

The new study furthers that work by pinpointing the specific tissue targeted by metformin. The findings suggest directing drugs or supplements to the gut could be an effective strategy for controlling blood sugar, Chandel said.

Chandel is also the David W. Cugell, MD, Professor of Medicine (Pulmonology and Critical Care), Biochemistry and Molecular Genetics and an investigator with the Chan Zuckerberg Initiative. The study's first author is Zach Sebo, a postdoctoral fellow in the Chandel lab who will soon start his own research group at the University of Kansas School of Medicine.

"Our study suggests that revisiting assumptions about metformin's mechanism may offer a more detailed understanding of how it works," Sebo said.

https://en.wikipedia.org/wiki/Metformin

Metformin's real power may be in the gut

Daily coffee drinking may slow biological aging of people with major mental illness

In continuation of my update on coffee

Drinking a maximum of 3–4 cups of coffee a day may slow the "biological" aging of people with severe mental illness, by lengthening their telomeres—indicators of cellular aging—and giving them the equivalent of 5 extra biological years, compared with non-coffee drinkers, finds research published in BMJ Mental Health.

But no such effects were observed beyond this quota, which is the maximum daily intake recommended by several international health authorities, including the NHS and the US Food and Drug Administration.

Telomeres sit at the end of chromosomes and perform a role similar to the plastic tips on the end of shoelaces. While telomere shortening is a natural part of the aging process, it seems to be accelerated in those with major psychiatric disorders, such as psychosis, schizophrenia, and bipolar disorder, note the researchers.

Study details and participant information

Telomeres are sensitive to environmental factors, including, possibly, diet. And coffee, when drunk in moderation, has been associated with various health benefits, prompting the researchers to explore whether it might influence the rate at which telomeres shorten in people with major mental ill health.

They included 436 adult participants from the Norwegian Thematically Organized Psychosis (TOP) study, recruited between 2007 and 2018: 259 had schizophrenia; the rest (177) had affective disorders, including bipolar disorder and major depressive disorder with psychosis.

Participants were asked how much coffee they drank every day and were grouped into four categories: zero (44); 1–2 cups; 3–4 cups (110); and 5 or more cups. And they were asked whether they smoked, and if so, for how long they had done so.

Participants who drank 5+ cups a day were significantly older than those who drank none or 1–2 cups a day. And those with schizophrenia drank significantly more coffee than those with an affective disorder.

Coffee intake is associated with telomere length in severe mental disorders, BMJ Mental Health (2025). DOI: 10.1136/bmjment-2025-301700

Daily coffee drinking may slow biological aging of people with major mental illness