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This could be why your weight-loss medication isn’t delivering results

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This could be why your weight-loss medication isn’t delivering results

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The skyrocketing popularity of GLP-1 receptor agonists has transformed the weight-loss industry, but not all shots are created equal in terms of how they work.

A study published in Nature investigated how genes affect the success of modern weight-loss drugs — specifically, GLP-1s like semaglutide and tirzepatide.

In analyzing genetic data and self-reported weight loss from over 27,000 users, researchers pinpointed a specific variation in the GLP-1 receptor gene (GLP1R) that acts as a “booster” for the drug’s effectiveness.

POPULAR WEIGHT-LOSS MEDICATIONS LINKED TO HIDDEN SIDE EFFECTS, STUDY FINDS

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Individuals carrying one copy of this variant lost an average of 1.6 pounds more than those without it, according to the findings.

This suggests that genetic testing could eventually help doctors steer sensitive patients toward medications they are more likely to tolerate.

Individuals carrying one copy of a specific genetic variant lost an average of 1.6 pounds more than those without it. (iStock)

“We believe these reports are a step forward in meeting an unmet need for a more informed and personalized approach to weight management,” said study co-author Noura Abul-Husn, chief medical officer at the 23andMe Research Institute in California, in a press release.

While this genetic “boost” is measurable, it remains relatively modest when compared to the total average weight loss of 24 pounds observed across the study population, the researchers noted.

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Beyond genetics, other factors such as age, sex and specific medications remain much stronger predictors of success.

For instance, the study found that women generally saw a higher body mass index (BMI) reduction (12.2%) compared to men (10.0%).

Traditional factors such as age, sex and specific medications remain much stronger predictors of success. (iStock)

The study may also reveal why certain patients experience stomach issues. Scientists identified a different genetic variant that was linked to increased reports of nausea and vomiting.

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The presence of this side effect did not impact the drug’s effectiveness, however. Patients with variants in the GLP1R and GIPR genes lost just as much weight as those without it; they simply felt more sick during the process, the study found.

WEIGHT-LOSS MEDICATIONS COULD IMPACT SEXUAL HEALTH IN UNEXPECTED WAYS

“GLP-1 treatment decisions are complex, and having access to clinical expertise to help contextualize your genetic results alongside your full health picture is exactly the kind of guidance this report is designed to support,” said Abul-Husn.

Patients with the variant lost just as much weight as those without it; they simply felt more sick during the process, the study found. (iStock)

Dr. Peter Balazs, MD, a hormone and weight-loss specialist serving the New York and New Jersey area, was not involved in the study but reiterated the role of the genetic variants in treatment response and side effects.

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“Notably, there appears to be a drug-specific effect: The GIPR variant associated with these side effects is observed with tirzepatide, but not with semaglutide,” he told Fox News Digital.

Balazs said he was surprised by the extremely wide nausea risk range (5%–78%). “Additionally, the drug-specific genetic dissociation was unexpected,” he added.

Study limitations

The data relied on participants reporting their own weight, which could be subject to bias.

“The data is self-reported and not medically verified, which may affect its reliability firstly,” Balazs told Fox News Digital. “It also does not account for key treatment variables, such as titration, discontinuation or dosing schedules.”

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The 23andMe participant pool may not reflect a diverse, real-world population, he added.

“The study also lacks data on important clinical endpoints, such as diabetes progression, and severe adverse effects, such as gastroparesis or pancreatitis,” Balazs pointed out. “Many of its findings also have not been supported by more clinically and statistically robust studies.”

Patients with the variant lost just as much weight as those without it; they simply felt more sick during the process, the study found. (iStock)

For example, a sub-study comparing these reports to objective iPhone health data suggested that participants might over-report their progress. While users reported an 11.8% loss, electronic data in that subset showed a 5.8% loss.

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As an observational study rather than a controlled clinical trial, it could not definitively prove that the genetic variants caused the difference in weight loss, only that they are associated with it, the researchers noted.

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“I think this article is interesting, raising the possibility of genetic factors, and the use of genetic testing incorporated into further decision-making when picking weight-loss medications,” Balazs said. “However, I would be careful to draw conclusions solely based on this study.”

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GLP-1s Don’t Work for Everyone: What To Know if You’re Not Seeing Results

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GLP-1s Don’t Work for Everyone: What To Know if You’re Not Seeing Results


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GLP-1 Not Working? Here’s Why and Alternatives That Can Help




















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Common eating habit may trigger premature immune system aging, study finds

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Common eating habit may trigger premature immune system aging, study finds

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Eating too much salt has long been linked to high blood pressure, but new research suggests it could trick the immune system into prematurely aging the blood vessels.

A preclinical study recently published in the Journal of the American Heart Association has identified a biological chain reaction that links a salty diet to cardiovascular decay.

Scientists at the University of South Alabama observed that mice on a high-salt diet experienced rapid deterioration in their blood vessel function.

HIGH SALT INTAKE LINKED TO FASTER MEMORY DECLINE IN ONE GROUP, STUDY FINDS

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After just four weeks of high sodium intake, the small arteries responsible for regulating blood flow lost their ability to relax, according to a press release.

The team found that the cells lining these vessels had entered a state of cellular senescence, a form of premature cellular aging in which cells stop dividing and release a mix of inflammatory signals that can damage surrounding tissue.

Excess salt has long been linked to high blood pressure, but a new study goes deeper into its effects on the cardiovascular system. (iStock)

The researchers tried to replicate this damage by exposing blood vessel cells directly to salt in a laboratory dish, but the cells showed no harmful effects.

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This suggests that salt isn’t directly causing damage to the vascular lining but that the real culprit may be the body’s own defense mechanism, the researchers noted.

Excess salt may trigger the immune system to release a molecule called interleukin-16 (IL-16), which acts as a messenger that instructs blood vessel cells to grow old before their time, according to the study.

Excess salt may trigger the immune system to release a molecule called interleukin-16, which acts as a messenger that instructs blood vessel cells to grow old before their time, according to the study. (iStock)

Once these cells age, they fail to produce nitric oxide, the essential gas that tells arteries to dilate and stay flexible.

To test whether this process could be reversed, the team turned to a class of experimental drugs known as senolytics.

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Using a cancer medication called navitoclax, which selectively clears out aged and dysfunctional cells, the researchers were able to restore nearly normal blood vessel function in the salt-fed mice, the release stated.

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By removing the decaying cells created by the high-salt diet, the drug allowed the remaining healthy tissue to maintain its elasticity and respond correctly to blood flow demands.

Excess salt may trigger the immune system into stopping the cells from dividing, the study suggests. (iStock)

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The study did have some limitations. The transition from mouse models to human treatment remains a significant hurdle, the team cautioned.

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Senolytic drugs like navitoclax are still being studied for safety, and the team emphasized that previous trials have shown mixed results regarding their impact on artery plaque.

Additionally, the researchers have not yet confirmed whether the same IL-16 pathway is the primary driver of vascular aging in humans.

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Healthy diets spark lung cancer risk in non-smokers as pesticides loom

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Healthy diets spark lung cancer risk in non-smokers as pesticides loom

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Eating a diet high in fruits and vegetables was found to have a surprising link to lung cancer among younger non-smokers, early research suggests.

The observational study, led by Jorge Nieva, M.D., of the USC Norris Comprehensive Cancer Center at Keck Medicine, was presented this month at the American Association for Cancer Research (AACR) annual meeting in San Diego. It has not yet been peer-reviewed. 

Researchers looked at dietary, smoking and demographic data for 187 patients who were diagnosed with lung cancer at age 50 or younger. 

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They found that among non-smokers, there was a link between healthier-than-average diets – rich in fruits, vegetables and whole grains – and the chance of lung cancer development.

Young lung cancer patients ate more servings of dark green vegetables, legumes and whole grains compared to the average U.S. adult, the researchers found.

Eating a diet high in fruits and vegetables was found to have a surprising link to lung cancer among younger non-smokers, early research suggests. (iStock)

The researchers hypothesized that pesticides applied to conventionally grown produce could be a possible factor in the disease association.

“Commercially produced (non-organic) fruits, vegetables and whole grains are more likely to be associated with a higher residue of pesticides than dairy, meat and many processed foods,” according to Nieva. He also noted that agricultural workers exposed to pesticides tend to have higher rates of lung cancer.

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HIDDEN VIRUS INSIDE GUT BACTERIA LINKED TO DOUBLED COLORECTAL CANCER RISK, STUDY FINDS

“There is a large subset of lung cancer patients whose disease is not caused by smoking,” Nieva told Fox News Digital.

The disease is becoming more common in non-smokers 50 and younger, especially women – despite the fact that smoking rates have been falling for decades, the researcher noted.

The researchers hypothesized that pesticides applied to conventionally grown produce could be a possible factor in the disease association. (iStock)

“These patients tend to have eaten much healthier diets before their diagnosis than the average American,” he went on. “We need to support research into understanding why Americans – and women in particular – who no longer smoke very much are still having lung cancer,” he said.

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DEATHS FROM ONE TYPE OF CANCER ARE SURGING AMONG YOUNGER ADULTS WITHOUT COLLEGE DEGREES

The study did have some limitations, Nieva acknowledged, primarily that it relied on survey data and was limited by the participants’ memories of their food intake.  

“Also, the survey participants were self-selected, and this could have biased the findings,” he told Fox News Digital.

“There is a large subset of lung cancer patients whose disease is not caused by smoking.”

The researchers did not test specific foods for pesticides, relying instead on average pesticide levels for certain types of food. Looking ahead, they plan to test patients’ blood and urine samples to directly measure pesticide levels, Nieva said.

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Although the study shows only an association and does not prove that pesticides caused lung cancer, Nieva recommends that people wash their produce before eating and choose organic foods whenever possible.

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“This work represents a critical step toward identifying modifiable environmental factors that may contribute to lung cancer in young adults,” said Nieva. “Our hope is that these insights can guide both public health recommendations and future investigation into lung cancer prevention.”  

“It is possible that the increased lung cancer risk could be due to pesticide exposure in whole farmed foods, but is by no means certain,” a doctor said. (AP Photo/Charlie Neibergall)

Dr. Marc Siegel, Fox News senior medical analyst, said the study is “interesting,” but that it “raises far more questions than it answers.”

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“It is a small study (around 150) and observational, so no proof,” the doctor, who was not involved in the research, told Fox News Digital.

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“It is possible that the increased lung cancer risk could be due to pesticide exposure in whole farmed foods, but it is by no means certain,” Siegel went on. “How much exposure is needed? How much of it gets into food and in which areas? This requires much further study.”

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Kayla Nichols, communications director for Pesticide Action & Agroecology Network, a distributed global network, said the organization agrees with the study’s conclusion that more research should be done on the rise in lung cancer, particularly in individuals eating diets higher in produce and fiber.

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“There is a large subset of lung cancer patients whose disease is not caused by smoking,” the researcher told Fox News Digital. (iStock)

“There is a bounty of existing research that already links pesticide exposure to increased risk of multiple types of cancers,” Nichols, who was also not involved in the study, told Fox News Digital. She called for more research on chronic, low-level exposures to pesticides, as well as more effective policies to protect the public from pesticide residues on food.

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The study was supported by the National Institutes of Health and the National Cancer Institute, as well as industry partners including AstraZeneca and Genentech, among others.

Fox News Digital reached out to several pesticide companies and trade groups for comment.

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