Scientists discover strange link between vitamin D and pain

In continuation of my update on Vitamin D

Women with low vitamin D levels may face a more painful recovery after breast cancer surgery and could require significantly more opioid medication afterward, according to research published online in the journal Regional Anesthesia & Pain Medicine.

The findings suggest that breast cancer patients with vitamin D deficiency (below 30 nmol/L) might benefit from taking vitamin D supplements before undergoing a radical mastectomy.

Researchers say growing evidence points to vitamin D playing an important role in how the body senses and regulates pain. Scientists believe this may be connected to the vitamin's anti inflammatory properties and its effects on the immune system. Vitamin D deficiency is also frequently seen in people with breast cancer.

Study Examined Pain After Breast Cancer Surgery

To explore the connection, researchers carried out a prospective observational study at Fayoum University Hospital in Egypt between September 2024 and April 2025.

The study included 184 women with breast cancer who were preparing to have surgery to remove one breast. Half of the participants had vitamin D deficiency (below 30 nmol/L), while the other half had vitamin D levels above 30 nmol/L. The two groups were otherwise similar, with average ages of 44 and 42.

Doctors and nurses caring for the patients did not know their vitamin D status. All participants received the hospital's standard treatment before, during, and after surgery.

During the operation, patients were given fentanyl to control acute pain. After surgery, everyone received intravenous paracetamol every eight hours. Patients were also able to self administer tramadol, another opioid pain medication, by pressing a control button.

Patients With Low Vitamin D Needed More Opioids

Pain levels were recorded immediately after surgery and again at 6, 12, 18, and 24 hours later. Researchers also tracked nausea, vomiting, sedation levels, and length of hospital stay.

Patients with vitamin D deficiency were three times more likely to experience moderate to severe pain during the first 24 hours after surgery compared with patients who had adequate vitamin D levels.

Researchers noted that none of the patients in either group reported severe pain of 7 or higher on the standard 0 to 10 pain scale. The difference was entirely related to a higher number of patients experiencing moderate pain levels between 4 and 6.

The vitamin D deficient group also required more opioid medication. On average, these patients received 8 μg more fentanyl during surgery, which researchers described as a modest increase.

However, after surgery, the difference became much larger. Patients with low vitamin D used an average of 112mg more tramadol than those with sufficient vitamin D levels. The medication was patient controlled, with doses capped at 50mg per hour.

Vitamin D and Recovery Complications

Opioid medications can lead to side effects such as nausea, vomiting, drowsiness, and confusion. They also carry risks of dependence and addiction.

The study found postoperative nausea occurred more often among patients with vitamin D deficiency. Vomiting was only reported in the deficient group, although researchers said the difference was too small to be considered statistically significant.

The researchers acknowledged several limitations. Because the study was observational and conducted at a single medical center, it cannot prove that low vitamin D directly caused the increase in pain. The team also did not measure inflammatory markers that might explain how vitamin D influences pain. In addition, information about anxiety, depression, cancer stage, previous treatments, and sleep problems before surgery was not collected.

Even with those limitations, the researchers concluded, "Vitamin D deficiency is associated with a higher occurrence of moderate to severe postoperative pain and increased opioid consumption in patients undergoing unilateral modified radical mastectomy."

They added, "Preoperative vitamin D supplementation in breast cancer patients with vitamin D levels below 30 nmol/L may have a role in modulating postoperative pain."

https://rapm.bmj.com/content/early/2026/05/04/rapm-2025-107495

Scientists discover strange link between vitamin D and pain 

Scientists discover strange link between vitamin D and pain

In continuation of my update on Vitamin D 

Women with low vitamin D levels may face a more painful recovery after breast cancer surgery and could require significantly more opioid medication afterward, according to research published online in the journal Regional Anesthesia & Pain Medicine.

The findings suggest that breast cancer patients with vitamin D deficiency (below 30 nmol/L) might benefit from taking vitamin D supplements before undergoing a radical mastectomy.

Researchers say growing evidence points to vitamin D playing an important role in how the body senses and regulates pain. Scientists believe this may be connected to the vitamin's anti inflammatory properties and its effects on the immune system. Vitamin D deficiency is also frequently seen in people with breast cancer.

Study Examined Pain After Breast Cancer Surgery

To explore the connection, researchers carried out a prospective observational study at Fayoum University Hospital in Egypt between September 2024 and April 2025.

The study included 184 women with breast cancer who were preparing to have surgery to remove one breast. Half of the participants had vitamin D deficiency (below 30 nmol/L), while the other half had vitamin D levels above 30 nmol/L. The two groups were otherwise similar, with average ages of 44 and 42.

Doctors and nurses caring for the patients did not know their vitamin D status. All participants received the hospital's standard treatment before, during, and after surgery.

During the operation, patients were given fentanyl to control acute pain. After surgery, everyone received intravenous paracetamol every eight hours. Patients were also able to self administer tramadol, another opioid pain medication, by pressing a control button.

Patients With Low Vitamin D Needed More Opioids

Pain levels were recorded immediately after surgery and again at 6, 12, 18, and 24 hours later. Researchers also tracked nausea, vomiting, sedation levels, and length of hospital stay.

Patients with vitamin D deficiency were three times more likely to experience moderate to severe pain during the first 24 hours after surgery compared with patients who had adequate vitamin D levels.

Researchers noted that none of the patients in either group reported severe pain of 7 or higher on the standard 0 to 10 pain scale. The difference was entirely related to a higher number of patients experiencing moderate pain levels between 4 and 6.

The vitamin D deficient group also required more opioid medication. On average, these patients received 8 μg more fentanyl during surgery, which researchers described as a modest increase.

However, after surgery, the difference became much larger. Patients with low vitamin D used an average of 112mg more tramadol than those with sufficient vitamin D levels. The medication was patient controlled, with doses capped at 50mg per hour.

Vitamin D and Recovery Complications

Opioid medications can lead to side effects such as nausea, vomiting, drowsiness, and confusion. They also carry risks of dependence and addiction.

The study found postoperative nausea occurred more often among patients with vitamin D deficiency. Vomiting was only reported in the deficient group, although researchers said the difference was too small to be considered statistically significant.

The researchers acknowledged several limitations. Because the study was observational and conducted at a single medical center, it cannot prove that low vitamin D directly caused the increase in pain. The team also did not measure inflammatory markers that might explain how vitamin D influences pain. In addition, information about anxiety, depression, cancer stage, previous treatments, and sleep problems before surgery was not collected.

Even with those limitations, the researchers concluded, "Vitamin D deficiency is associated with a higher occurrence of moderate to severe postoperative pain and increased opioid consumption in patients undergoing unilateral modified radical mastectomy."

They added, "Preoperative vitamin D supplementation in breast cancer patients with vitamin D levels below 30 nmol/L may have a role in modulating postoperative pain.

https://rapm.bmj.com/content/early/2026/05/04/rapm-2025-107495

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

Scientists discover strange link between vitamin D and pain | ScienceDaily

New chemical kills 95% of termites without harming humans

Drywood termites are experts at staying out of sight. They live inside wooden structures, quietly feeding and expanding their colonies where homeowners may not notice them until damage is already underway. But their hidden lifestyle also depends on a vulnerable biological process: molting.

Researchers at the University of California, Riverside have shown that bistrifluron, a chemical that blocks the formation of new termite exoskeletons, can destroy drywood termite colonies by interfering with the insects' ability to grow. The findings were published in the Journal of Economic Entomology. In laboratory testing, the treatment killed about 95 percent of a colony without the mammal toxicity concerns linked to many traditional termite control methods.

A Safer Way To Target Termites

"This chemical is more environmentally friendly than ones traditionally used for drywood termite infestations," said Nicholas Poulos, corresponding author of the paper and a doctoral student in UCR's Department of Entomology. "It's specific to insects and can't harm humans."

The reason the chemical is so targeted comes down to the termite body plan. Humans have bones inside their bodies. Termites wear their support system on the outside in the form of an exoskeleton. That outer shell is built largely from chitin, a tough natural material also found in fungal cell walls, fish scales, and the beaks of squids and octopi.

For insects, chitin is essential. It gives the exoskeleton strength, helps shield the body, and provides anchoring points for muscles. When termites grow, they must shed their old exoskeleton and build a new one. Drywood termites go through this process about seven times during their lives.

Bistrifluron interrupts that step. Instead of poisoning termites in a broad, fast acting way, it prevents them from making the chitin they need for their next protective shell.

"Once the termites reach a certain stage, they have to molt. They cannot avoid that," said Dong-Hwan Choe, UCR entomology professor and senior paper author. "With a lethal dose of this chemical, they'll try to shed their old exoskeleton but won't have a new one ready to protect them."

Termites Spread the Treatment Themselves

The effect is not instant. The researchers saw that bistrifluron first made the termites less active and reduced their feeding. Over time, the chemical blocked successful molting, and the insects died.

The 2025 study tested three chitin synthesis inhibitors against the western drywood termite, Incisitermes minor. Bistrifluron worked faster than chlorfluazuron and noviflumuron at the tested rates. In one no choice test, bistrifluron produced 99 percent mortality over 60 days. In a choice test using a 0.1 percent rate, it produced 96 percent mortality over the same period.

The most important part may be how the chemical travels. After termites fed on treated wood, they passed material to other members of the colony. In transfer tests, even when only 5 percent of termites had been exposed, the groups reached 100 percent mortality by day 90. The study reported that food material moved from exposed donor termites to unexposed recipients within 24 to 48 hours.

That finding fits with newer UC Riverside work highlighting how western drywood termites share food and essential gut microbes through proctodeal trophallaxis, a mouth to anus feeding behavior that is difficult to observe because the insects live almost entirely inside wood. Those hidden social behaviors can make infestations hard to detect, but they may also help treatments spread once termites contact treated material.

"It's been successfully used on subterranean termites, which are also important structural pests," Choe said. "But native western drywood termites are also important, especially in California."

A Slower Collapse With Big Advantages

Once drywood termites consume the treated wood, the compound can move through the colony as termites interact. Full colony collapse takes roughly two months, making it slower than some conventional methods. But the tradeoff could be worth it: lower toxicity, more targeted action, and the potential for a localized treatment that does not require tenting an entire home.

"We believe this method of spot treatment can kill a larger colony and spread more easily than current termite control methods," Choe said. "You don't have to apply too much to get a very good result. The chitin synthesis inhibitors show promise as localized treatment for drywood termites."

Traditional fumigation remains a major burden for homeowners. It can be toxic, disruptive, and stressful. People often have to bag food, leave the house, and wait before returning. It also does not prevent termites from coming back later.

"Low-impact strategies like this one will become an attractive option in many cases. Furthermore, the chemical may stay active in the wood for some time, potentially providing protection from future infestations," Choe said.
A Chemical Lure Could Make Treatment StroThe UCR team has also explored another clever way to improve termite control: using scent to draw termites toward treated wood. In earlier work, Choe's lab studied pinene, a pleasant smelling chemical released by forest trees. To western drywood termites, pinene can signal food.

When termites follow that scent into insecticide treated wood, the treatment becomes more effective. A 2025 patent application from UCR describes the use of pinenes to improve localized insecticide injections against western drywood termites. It states that adding pinene to localized treatments killed termites more quickly and increased final mortality compared with insecticide alone. The application also suggests that pinene could allow wider spacing between drill holes and may reduce the time, labor, and amount of insecticide needed for treatment.

"We saw significant differences in the death rates using insecticide alone versus the insecticide plus pinene," said Choe. "Without pinene, we got about 70% mortality. When we added it in, it was over 95%."

Making It Practical for Homes

The bistrifluron study used acetone to dissolve the chemical before applying it to wood. That worked for the research, but it is not ideal for real world use because acetone is flammable and has a strong odor.

"We are working to make it more feasible for practical application in real life scenarios," Poulos said.

That next step matters because western drywood termites are a serious structural pest. They are native to northern Mexico and California, and they are especially important in California. The species has also been introduced to other regions, including Hawaii, New York, Florida, Canada, China, Japan, Korea, and Australia, according to the 2025 study. Movement of lumber and other wood products helps transport termites, while their concealed lifestyle inside wood makes them difficult to manageClimate change may add to the problem. As temperatures shift, the termites may be able to expand into places that were once less suitable for them.

"As we move lumber around the world, the termites are constantly transported to new locations. If they find the climate there acceptable, the problem will spread," Choe said. "In areas where these termites are common, it's just a matter of time before homes are infested, so this study is a good initial step toward alternative strategies for controlling them."

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

New chemical kills 95% of termites without harming humans | ScienceDaily

New drug combination doubles down on Alzheimer's treatments

A new study finds that combining the current medications for Alzheimer’s disease with small molecules derived from micronutrients found in grapes, berries, peanuts and turmeric is a safer and more effective way to treat the disease.

Individuals with Alzheimer’s have a buildup of toxic amyloid proteins in the brain. Researchers from the School of Pharmacy at the University of Waterloo combined amyloid-destroying small molecules with anti-amyloid antibodies that are already used in Alzheimer’s treatment. They found that it neutralized the clumping of proteins that accumulate in the brain, leading to better outcomes.

Alzheimer’s is the major cause of dementia. Dementia affects nearly 750,000 people in Canada, with a million cases expected by 2030. Alzheimer’s has no cure and current medications only relieve a patient’s symptoms. Anti-amyloid antibody therapies on their own can slow the disease, but they also come with risks that can be fatal, including brain swelling and bleeding.

“We already know the small molecules resveratrol or curcumin, which are found in some common foods, block the buildup of amyloid,” said Dr. Praveen Nekkar Rao, a professor in the School of Pharmacy at Waterloo. “What’s new and exciting is our combination of these molecules with the anti-amyloid antibodies. This approach could allow clinicians to use lower doses of antibodies, potentially reducing the risk of serious treatment-related side effects.”

Since there are few effective treatments for Alzheimer’s, researchers at Waterloo studied whether using two treatments together could work better than using just one. They chose resveratrol and curcumin because they are natural compounds known to reduce amyloid buildup and inflammation.

curcumin

Resveratrol

“I was inspired by chemotherapy, which involves taking multiple medications for effective treatment,” Nekkar Rao said. “Alzheimer’s is a complex disease, but there are very few combination therapy approaches. Our results show that the way forward is definitely combination therapy.”

The researchers emphasize that the study does not suggest that people should start consuming resveratrol or curcumin to prevent or treat dementia. You would have to consume an unsafe amount in order to reach the brain. The next phase of the research will focus on designing next-generation drugs that can reach the brain more effectively, interact favourably with amyloids and pair seamlessly with antibody treatments.

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

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

New drug combination doubles down on Alzheimer's treatments

Merck Scientists Publish Landmark Paper on Novel Method for Large-Scale Biocatalytic Synthesis of Investigational Oral PCSK9 Inhibitor, Enlicitide Decanoate

Merck (NYSE: MRK), known as MSD outside the United States and Canada, announced the publication of work describing the large-scale synthesis of enlicitide decanoate, the company’s investigational oral PCSK9 inhibitor, using a tailored suite of enzymes in the latest issue of the peer reviewed journal Science.

• Publication in Science magazine outlines blueprint for the scalable
•  synthesis of complex orally available macrocyclic peptides
• Enlicitide, a novel macrocyclic peptide, has the potential to be the first approved oral PCSK9 inhibitor

“Macrocyclic peptides have the potential to unlock new opportunities to develop oral treatment options for challenging therapeutic targets and broaden patient access,” said Dr. Dean Y. Li, president, Merck Research Laboratories. “The scalable production process for enlicitide described in this publication showcases Merck’s scientific capabilities and underscores our sustained commitment to helping address the global cardiovascular epidemic.”

In this publication, Merck scientists detail the biocatalytic assembly of enlicitide using a suite of enzymes that catalyze selective peptide fragment formation, coupling, and macrocyclization. Together with efficient purifications using crystallization, this strategy enabled the manufacture of a product that would not be possible with traditional synthetic methods. The method described offers a sustainable blueprint for the scalable development of complex macrocyclic peptide therapeutics, environmental advantages and manufacturing efficiencies that support efforts to expand patient access.

About biocatalysis

Biocatalysis describes the process of using enzymes to conduct chemical synthesis. Biocatalysis offers environmental sustainability advantages over chemical catalyst methods. For more than 25 years Merck has invested in the development of biocatalysis including the generation of novel enzymes for the synthesis and novel manufacturing of pharmaceutical products at scale.

About macrocyclic peptides

Over a decade ago, an interdisciplinary team of Merck scientists were challenged to create a type of medicine that may provide the potency and selectivity of a biologic therapy but in the form of a pill. Macrocyclic peptides are intricate ring-shaped molecules with the ability to target and disrupt protein-protein interactions while retaining oral bioavailability. For more information regarding our approach to macrocyclic peptides, visit merck.com

About enlicitide and PCSK9

Enlicitide has the potential to be the first approved oral PCSK9 inhibitor. It is designed to lower LDL-C via the same biological mechanism as currently approved monoclonal antibody, injectable PCSK9 inhibitors but in a daily pill form. Enlicitide is a novel macrocyclic peptide candidate that binds to PCSK9 and inhibits the interaction of PCSK9 with LDL receptors.

PCSK9 plays a key role in cholesterol homeostasis by regulating levels of the LDL receptor, which is responsible for the uptake of cholesterol into cells. Inhibition of PCSK9 is designed to prevent the interaction of PCSK9 with LDL receptors. This results in greater numbers of LDL receptors available on the cell surface to remove LDL cholesterol from the blood.

About the CV epidemic and atherosclerotic cardiovascular disease

The silent CV epidemic is the leading cause of deaths globally, contributing to the majority of heart attacks and strokes, and deaths related to CV continue to rise. ASCVD accounts for 85% of CV deaths. It is caused by the buildup of plaque within the arteries, leading to narrowed or blocked blood vessels that can result in serious CV events such as heart attacks and strokes as well as coronary artery disease, peripheral artery disease and cerebrovascular disease.

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

Merck Scientists Publish Landmark Paper on Novel Method for Large-Scale Biocatalytic Synthesis of Investigational Oral PCSK9 Inhibitor, Enlicitide Decanoate 

Vitamin D Deficiency Linked to Fatigue, Studies Show

In continuation of my update on Vitamin D

Prevalence and Link to Fatigue

Approximately 40% to 75% of the teen and adult population in the United States is deficient in vitamin D, according to Raymond Francis in “The Great American Health Hoax.” ^[1] Low energy and occasional fatigue are commonly reported among individuals with low vitamin D status, according to a report on the silent epidemic of nutrient deficiencies. ^[2] The scale of the problem is vast, with estimates suggesting that nearly half of all adults may have insufficient levels, the report stated.

Vitamin D deficiency is not confined to a single demographic. Factors such as limited sun exposure, darker skin pigmentation, and indoor lifestyles contribute to widespread insufficiency, researchers said. The link between low vitamin D and fatigue has been documented in multiple studies, though many individuals remain unaware of their own deficiency status.

Mechanism: Vitamin D and Cellular Energy

Vitamin D supports mitochondrial function, which is responsible for cellular energy production, according to research cited in an article on fatigue and mitochondria. ^[3] The mitochondria act as the powerhouses of the cell, generating adenosine triphosphate (ATP) from nutrients. A deficiency may disrupt mitochondrial efficiency, contributing to feelings of lethargy, experts said. ^[4]

The role of mitochondria in energy production is central to understanding why vitamin D insufficiency can lead to persistent tiredness. As noted in the book “Dissolving Illusions,” proper mitochondrial metabolism is essential for normal cellular function, and any disruption can manifest as weakness or apathy. ^[5] Although that text focuses on vitamin C, the principle applies broadly to nutrients that support mitochondrial health, including vitamin D.

Supporting Studies

Multiple studies have reported a connection between low vitamin D levels and fatigue. A 2016 study of 200 female nurses in Iran found that low vitamin D levels accounted for 13% to 18% of reported prolonged tiredness, according to a review of nutrient deficiencies. ^[2] A 2019 study published in Nutrients similarly found that older adults with occasional fatigue had a significantly worse vitamin D status than those without fatigue, the review added. ^[2]

Other research has reinforced these findings. In a broader analysis, researchers noted that individuals frequently reporting low energy were more likely to have suboptimal vitamin D levels compared to their peers, according to an article on fatigue and mitochondrial function. ^[4] The consistency of the association across different populations suggests a robust relationship, though causation requires further investigation, scientists said.

Other Health Impacts

Beyond fatigue, vitamin D deficiency has been linked to several other health issues. Vitamin D directly modulates the body’s innate and adaptive immune responses, according to a review of the critical role of vitamin D in immune function. ^[6] Immune cells require adequate vitamin D to respond efficiently to threats, the review stated. Low levels have also been associated with increased susceptibility to infections and longer recovery times.

Vitamin D also influences bone health and cellular aging. Raymond Francis wrote that vitamin D is essential for calcium metabolism, supports bone health, helps control blood sugar, and protects against cancer. ^[1] The nutrient significantly increases the production of telomerase, an enzyme that repairs telomeres and slows aging, according to the same source. ^[1] These wide-ranging effects underscore the importance of maintaining optimal levels.

Solutions: Increasing Vitamin D Levels

Optimal vitamin D levels are considered to be above 50 nanograms per milliliter, and supplementation with 5,000 IU daily is recommended by some nutritionists, according to an interview on health testing and supplementation. ^[7] At-home blood tests can help individuals assess their current levels, the interview stated. ^[7] Testing allows for personalized dosing rather than generic recommendations.

The safety of higher vitamin D doses has been affirmed by recent reassessments. A news report noted that a “schoolboy error” in earlier guidelines led to overly cautious upper limits, and the Academy of Medicine has since acknowledged that higher intakes are not toxic for most people. ^[8] Dietary sources such as fatty fish, egg yolks, and fortified foods can also contribute, though supplementation is often the most reliable way to correct a deficiency, experts said.

Conclusion

Individuals experiencing unexplained fatigue may consider testing their vitamin D levels, clinicians advised. ^[7] Supplementation and dietary changes can help restore levels to the optimal range, though consulting a healthcare provider is recommended before starting any regimen, according to the interview. ^[7]

The evidence linking vitamin D deficiency to fatigue is supported by prevalence data, mechanistic studies, and clinical observations. Given the high rates of insufficiency in the general population, testing and appropriate supplementation offer a straightforward strategy for addressing a common but often overlooked contributor to low energy, researchers concluded.

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

Vitamin D Deficiency Linked to Fatigue, Studies Show 

Daily orforglipron treatment reduces weight and blood sugar in seniors

In continuation of my update on orforglipron

A new analysis to be presented at this year's European Congress on Obesity (ECO 2026, Istanbul, Turkey, 12-15 May) examined daily oral orforglipron treatment for the treatment of obesity, with or without diabetes, in users aged 65 years and over, with results and a safety profile similar to that seen in the ATTAIN clinical trial programme population. Lead author for this post-hoc analysis is Dr Deborah Horn, Director of the Center for Obesity Medicine and Metabolic Performance at McGovern Medical School at UTHealth Houston, Houston, Texas, USA, and colleagues.

Limited clinical data exist on the use of incretin-based obesity management medications in older adults with or without type 2 diabetes (T2D), and a lack of specific analyses related to older users could be a factor that could make providers or patients in this age group hesitant when considering therapy choices.

Orforglipron is a novel small-molecule, non-peptide, oral glucagon-like peptide-1 receptor agonist (GLP-1 RA) developed by Eli-Lilly and Company (Lilly), who sponsored these analyses. The drug was approved by the US Food and Drug Administration for chronic weight management on April 1, 2026.

Orforglipron demonstrated significant weight reduction vs. placebo in the phase 3, randomised, double-blind, multinational ATTAIN-1 and ATTAIN-2 clinical trials in participants with obesity or obesity and T2D, respectively. In this new analysis of those trials, the authors evaluated efficacy and safety of orforglipron versus placebo in a sub-group of participants aged 65 years and older from ATTAIN-1 and ATTAIN-2.

The ATTAIN-1 and ATTAIN-2 global clinical trials evaluated once-daily orforglipron 6 mg, 12 mg, or 36 mg vs. placebo as an adjunct to healthy diet and physical activity in participants from 9 and 10 countries, respectively. In this sub-group analysis, efficacy outcomes were analysed separately for each trial, and safety data were pooled. The primary endpoint was percent change in body weight from baseline to week 72.

In ATTAIN-1 and ATTAIN-2, 616 randomised participants were ≥65 years of age (n=196 and 420, respectively). Of those, 613 received treatment (orforglipron 6 mg, n=118; 12 mg, n=135; 36 mg, n=146; placebo, n=214). And 79.1% of ATTAIN-1 and 86.2% of ATTAIN-2 participants had hypertension as a comorbidity.

At Week 72, the percent change in weight from baseline in users aged 65 and over in ATTAIN-1 (participants with obesity and without T2D) was –7.9%, –11.3%, and –13.0% with orforglipron 6 mg, 12 mg, and 36 mg, respectively, vs. –1.6% with placebo, all statistically significant findings. Similar results were found for those users aged 65 years and over with T2D and obesity in ATTAIN-2: orforglipron 6 mg: –7.5%; 12 mg: –8.3%; 36 mg: –12.2%; placebo: –2.3% again with all results statistically significant.

Participants with T2D experienced reductions from baseline in glycated haemoglobin (HbA1c – a measure of blood sugar control) of –1.5%, –1.6%, and –1.7% with 6 mg, 12 mg, and 36 mg orforglipron, respectively, vs. –0.1% with placebo. BMI, waist circumference, triglycerides, non-HDL cholesterol, and health-related quality of life also improved in orforglipron vs. placebo treatment groups in participants with or without T2D. 

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

Daily orforglipron treatment reduces weight and blood sugar in seniors

Semaglutide shows sustained weight loss benefits in older adults

In continuation of my update on semaglutide

A new analysis of the STEP trails carried out by semaglutide manufacturer Novo Nordisk has analysed various trials to show the safety and efficacy of the obesity drug semaglutide in older adults (over 65 years), and found similar efficacy and safety as in the general trial populations . The study is by Prof Luca Busetto from the University of Padova in Italy and colleagues including from Novo Nordisk, who sponsor this new study.

Individuals of advanced age with obesity represent a vulnerable group, often presenting with comorbidities and frailty, and being at risk of adverse events (AEs). Information on the use of glucagon-like peptide-1 (GLP-1) receptor agonists including semaglutide in this population is limited; therefore, the authors decided assessed the efficacy and safety of once-weekly subcutaneous semaglutide 2.4 mg in individuals aged 65 years and over.

The analysis pooled together data from the STEP 1, 3, 4, 5, 8 and 9 trials (only in people with obesity or overweight, not diabetes, because weight loss in obesity drug trials is always lower in people with diabetes than without – thus results cannot be compared or mixed). It included participants aged ≥65 years with body mass index of at least 30 kg/m², or at least 27 kg/m² and at least 1 obesity-related complication (without diabetes) who were randomised to receive semaglutide 2.4 mg or placebo. All participants received lifestyle intervention and, in STEP 3, intensive behavioural therapy. Endpoints were assessed from baseline to week 68 and included percentage change in body weight; proportion of participants achieving categorical body weight reductions (≥10%, ≥15%, ≥20%); change in waist circumference; proportion of participants achieving waist to height ratio (WHtR) <0.53; shift in BMI category; and changes in cardiometabolic risk factors (glucose parameters, blood pressure, serum lipids and hs-CRP). Adverse events (AEs) were also assessed.

Of the total population in the selected trials (N=4523), 358 participants (8%) were aged 65 years or older and included in the analysis (semaglutide 2.4 mg, n=248; placebo, n=110), with most (90%) being aged 65–74 years (and the others 75 years and over). Across the pooled semaglutide and placebo groups at baseline, mean age was 69 years, bodyweight was 99.0 kg, BMI was 36.6 kg/m² and waist circumference was 115 cm; 72% were female.

At week 68, there was a mean −15.4% change in body weight for semaglutide 2.4 mg vs −5.1% for placebo, and a mean −14.3 cm vs −6.0 cm change in waist circumference, respectively. Proportions of participants achieving body weight reduction thresholds in the semaglutide 2.4 mg vs placebo groups were 66.5% vs 15.5% (at least 10%), 46.8% vs 6.4% (at least 15%) and 28.6% vs 2.7% (at least 20%), respectively.

In the semaglutide 2.4 mg group, 11.3% achieved a WHtR <0.53, compared with 4.5% with placebo. A greater proportion of semaglutide-treated participants improved their BMI category from baseline to week 68 compared with placebo (see Figure full abstract). A BMI of <27 kg/m² (so called healthy weight) was achieved by 27.0% of participants in the semaglutide group vs 5.5% in the placebo group; and the proportion of elderly patients in the overweight and obesity class I, II and III categories all fell in the semaglutide group at week 68 due to the increase in participants who had reached a healthy weight.

For participants achieving both a BMI of 27 or less and a WHtR of <0.53 these values were 10.5% vs 2.7%, respectively. Greater improvements in cardiometabolic risk factors were observed with semaglutide 2.4 mg vs placebo (see Table full abstract), including blood pressure, blood fats, cholesterol and glycated haemoglobin (HbA1c – a measure of blood sugar control used in diagnosis of diabetes).

Proportions of participants experiencing AEs and serious AEs in the semaglutide 2.4 mg vs placebo groups were similar for AEs overall (89.1% vs 84.5%), but higher for semaglutide re: serious AEs - 19.0% vs 12.7%, respectively. Constipation and dizziness rates (known side effects of this class of drug) were higher with semaglutide, while fractures and hypoglycaemia were comparable to placebo, both affecting less than 1% in each group.

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

Semaglutide shows sustained weight loss benefits in older adults

Glutamic Acid Helps Fresh-Cut Potatoes Stay Fresh by Silencing Browning Genes | Newswise

In continuation of my update on Glutamic acid 

The study identified a transcriptional regulatory module, StbZIP53-like2–StERF091, that suppresses the activity of key polyphenol oxidase genes linked to browning. By showing how glutamic acid activates this gene-control system, the work provides a clearer molecular basis for safer anti-browning strategies and may support the future development of quality-preserving treatments for fresh-cut potato products and other minimally processed vegetables.

Fresh-cut potatoes are increasingly popular because they fit modern food habits, but their shelf life is limited by rapid enzymatic browning after cutting. Existing methods to control browning include chemical, physical, and biological approaches, yet each has drawbacks. Some chemicals raise food-safety concerns, while physical treatments may cause off-flavors, and many biological methods are still difficult to commercialize. Earlier work had already shown that glutamic acid could reduce browning in fresh-cut potatoes, but the molecular mechanism remained unclear. That unresolved question made it necessary to investigate how glutamic acid regulates browning-related genes and upstream transcription factors in fresh-cut potato tissue.

A study (DOI:10.48130/ph-0026-0004) published in Plant Hormones on 20 March 2026 by Jingying Shi’s & Zunyang Song’s team, Shandong Agricultural University, demonstrates that glutamic acid-induced StbZIP53-like2 and StERF091 form a cooperative regulatory module that represses StPPO2 and StPPO3, thereby alleviating browning in fresh-cut potatoes.

The team first prepared fresh-cut potato shreds and compared untreated samples with samples immersed in a glutamic acid solution, then stored them at 4 °C and collected tissues across multiple time points. They measured ethylene production, performed RNA-seq and RT-qPCR analyses, and screened for transcription factors whose expression changed under glutamic acid treatment. Among 11 bZIP genes detected, StbZIP53-like2 stood out because its expression was strongly induced by glutamic acid. Subcellular localization assays showed that this protein is localized in the nucleus, consistent with its proposed role as a transcription factor. The researchers then examined whether StbZIP53-like2 directly controlled known browning-associated genes. Dual-luciferase assays showed that it repressed the promoter activity of StPPO3, while EMSA and yeast one-hybrid experiments confirmed direct binding to the C-box motif in the StPPO3 promoter. To identify interacting partners, the team screened a cDNA library and found StERF091, another glutamic acid-induced transcription factor. Yeast two-hybrid, GST pull-down, and co-immunoprecipitation assays together demonstrated that StbZIP53-like2 physically interacts with StERF091 both in vitro and in vivo. Like StbZIP53-like2, StERF091 was also localized in the nucleus. Next, the group tested the function of StERF091 in regulating browning genes. They found that StERF091 repressed the promoter activities of StPPO2 and StPPO3, but not StPPO7. EMSA and yeast one-hybrid assays further showed that StERF091 directly binds the GCC-box motifs in the StPPO2 and StPPO3 promoters. Most importantly, co-expression assays revealed that when StbZIP53-like2 and StERF091 acted together, repression of StPPO2 and StPPO3 became stronger than with either factor alone. This demonstrated that the two proteins form a functional inhibitory module that amplifies the anti-browning response triggered by glutamic acid.

Overall, the study shows that glutamic acid alleviates the browning of fresh-cut potatoes by inducing two transcriptional repressors, StbZIP53-like2 and StERF091, which cooperate to suppress StPPO2 and StPPO3. The findings move beyond a simple observation that glutamic acid works and explain why it works at the molecular level. This insight may help guide future preservation technologies aimed at extending the shelf life, visual quality, and commercial value of fresh-cut produce.

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

Glutamic Acid Helps Fresh-Cut Potatoes Stay Fresh by Silencing Browning Genes 

Legumes and soy foods may help reduce hypertension risk

In continuation of my continuation of my update on soy ..

A higher dietary intake of soy and legumes is linked to a lower risk of high blood pressure, finds a pooled data analysis of the available evidence, published in the open access journal BMJ Nutrition Prevention & Health.

And the optimal daily amount may be around 170 g of legumes, which include peas, lentils, chickpeas and beans, and 60 to 80 g of soy foods, examples of which include tofu, soy milk, edamame, tempeh, and miso, the findings indicate.

Legumes and soy foods have been associated with an overall lower risk of cardiovascular disease, but the evidence on their potential for lowering high blood pressure is mixed and needs to be systematically quantified, explain the researchers.

To explore this further, the researchers scoured databases for relevant studies published up to June 2025, and found 10 publications that included data from 12 prospective observational studies.

Five studies were from the USA, 5 from Asia (China, Iran, South Korea and Japan), and 2 were from Europe (France and the UK). Nine studies included both men and women, 2 included only women, and 1 included only men.

The number of study participants ranged from 1152 to 88,475 and the number of cases of high blood pressure ranged from 144 to 35,375.

Pooled data analysis of the study findings showed that higher daily intake of legumes and soy foods was associated with a lower risk of developing high blood pressure.

Compared with those with a low intake of legumes, those with a high intake were 16% less likely to develop high blood pressure. Similarly, those with a high intake of soy foods were 19% less likely to develop the condition than those with a low intake.

When assessing the association between quantity and lower risk, a linear reduction (30%) emerged for legumes up to around 170 g/day, while most of the reduction in risk (28-29%) for soy foods was observed at between 60 and 80 g/day, with no further reduction in risk at higher intake.

One hundred grams of legumes/soy is equivalent to a serving size of about one cup or 5–6 tablespoons of cooked beans, peas, chickpeas, lentils, soybeans or a palm-size serving of tofu, explain the researchers.

Using World Cancer Research Fund evidence grading criteria for evaluating the likelihood of causality, the researchers consider the overall evidence to indicate a probable causal relationship between both legume and soy intake and a reduced risk of high blood pressure.

There are plausible explanations for the findings, they say. Legumes and soy are high in potassium, magnesium, and dietary fiber, all of which are known for their blood pressure lowering properties.

And recent research has suggested that the fermentation of soluble fiber from legumes and soy produces short-chain fatty acids that influence blood vessel dilation, while the isoflavone content of soy also seems to help lower blood pressure, they explain.

The researchers acknowledge various limitations to their findings, including the variability of the studies in the pooled data analysis. This included differences in legume types, levels of intake, preparation methods, dietary contexts, and the definition of high blood pressure.

"Despite these limitations, the findings of this meta-analysis have major public health implications, given the alarming global increase in hypertension prevalence," they point out.

"Current legume consumption across Europe and the UK remains below dietary recommendations, with average intakes of only 8–15 g/day, far below the recommendations of 65 to 100 g/day recommended for overall cardiovascular health," they add.

"Although further large-scale cohorts are needed for confirmation, these findings provide further evidence in support of dietary recommendations to the public to prioritise and integrate legumes and soy foods as healthy protein sources in the diet," they conclude.

"This research strengthens the evidence base for the cardioprotective benefits of plant-based diets. The authors have significantly added to the case for using legumes and soy as primary dietary strategies to mitigate the global burden of hypertension," comments Professor Sumantra Ray, chief scientist and executive director of NNEdPro Global Institute for Food, Nutrition and Health, which co-owns BMJ Nutrition Prevention & Health.

"The strengths of the study lie in its rigorous dose-response analyses, which offer practical dietary targets for use in public health guidelines and clinical practice. But we can't entirely rule out the influence of unmeasured influential factors. And the plateauing of benefits for soy at 60–80 g/day warrants further investigation, as it remains unclear if this reflects a true biological limit or is a byproduct of the smaller number of studies available for analysis."

Legumes and soy foods may help reduce hypertension risk

Nicotinamide Linked to Lower Melanoma Risk Post Skin Cancer

In continuation of my update on Nicotineamide

Nicotinamide supplementation was associated with a decreased risk for melanoma among patients with a history of other skin cancers, according to a retrospective cohort study of more than 33,000 veterans.

The study, which won a first-prize poster award at the American Academy of Dermatology (AAD) 2026 Annual Meeting, “suggests that nicotinamide could potentially be effective for primary prevention of melanoma among patients who have had a prior nonmelanoma skin cancer,” noted Lee Wheless, MD, PhD, one of the senior authors, an assistant professor of dermatology at Vanderbilt University and a staff physician with the Tennessee Valley Healthcare System VA Medical Center, both in Nashville, Tennessee.

The effect of nicotinamide, at a dose of 500 mg twice daily, was statistically significant for invasive, but not in situ, melanoma, and it was consistent in both sun-exposed and sun-protected areas, he told Medscape Medical News.

The retrospective cohort study used data from the Veterans Affairs (VA) Corporate Data Warehouse from January 1, 2007, to December 31, 2024. It included a total of 33,581 patients with one or more prior skin cancers of any type. The cohort was predominantly White and men, with comparable mean ages (77.5 years in the exposed group vs 77.1 years in the unexposed group).

The US Department of VA offers nicotinamide, a vitamin B3 derivative, on formulary. Patients exposed to nicotinamide 500 mg twice daily were propensity score matched to unexposed patients based on “numerous skin cancer risk variables to make sure risks at specific timepoints in the patients’ lives matched up,” explained Wheless.

Baseline matching variables included age, sex, race, age at first skin cancer, number and year(s) of prior skin cancers of any type, number of dermatology visits after baseline, chronic lymphocytic leukemia, solid organ transplantation, exposure to acitretin, and field therapy.

More...

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

Nicotinamide Linked to Lower Melanoma Risk Post Skin Cancer

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