Benefits, risks linked to popular weight-loss drugs

 

Demand for weight-loss medications sold under brand names such as Ozempic and Wegovy continues to surge, with a recent study reporting one in eight Americans has taken or is currently using the drugs to treat diabetes, heart disease or obesity.

Formally, these drugs are known as glucagon-like peptide-1 receptor agonists (GLP-1RA) and include Mounjaro and Zepbound. Informally, media, patients and even some physicians have dubbed GLP-1 medications as “miracle drugs” because of the profound weight loss among users. While these health benefits are well established, information is sparse on the drugs’ effects across the body’s organ systems.

Now, scientists at Washington University School of Medicine in St. Louis and the Veterans Affairs (VA) St. Louis Health Care System have systematically evaluated health outcomes among more than 2 million people with diabetes taking the popular weight-loss drugs. They found widespread associations with benefits to cognitive and behavioral health, while also revealing increased risks for pancreatitis and kidney conditions, among others.

The study is published Jan. 20 in the journal Nature Medicine.

“Given the drugs’ newness and skyrocketing popularity, it is important to systematically examine their effects on all body systems — leaving no stone unturned — to understand what they do and what they don’t do,” said the study’s senior author, Ziyad Al-Aly, MD, a clinical epidemiologist and nephrologist who treats patients at the WashU Medicine-affiliated John J. Cochran Veterans Hospital in St. Louis.

“Our approach has allowed us to build a comprehensive atlas mapping the associations of GLP-1RA spanning all organ systems,” he said. “The study’s results provide insights into some known and previously unrecognized benefits and risks of GLP-1RA that may be useful to inform clinical care and guide research agendas.”

The drugs, taken once a week by injection, simulate naturally produced hormones that curb appetite and slow digestion, creating longer-lasting satiety. A healthy diet and exercise also assist with weight loss.

For the study, WashU Medicine researchers analyzed de-identified medical records in a database maintained by the U.S. Department of Veterans Affairs. They compared 175 health outcomes between veterans who took GLP-1RA drugs to treat their diabetes and those who took more traditional medications sold under brand names such as Jardiance, Glipizide and Januvia.

Altogether, the dataset examined more than 2 million veterans who were treated for diabetes from Oct. 1, 2017, to Dec. 31, 2023. Patients included people of diverse ages, races and sexes.

GLP-1RA drugs were associated with significant benefits to neurological and behavioral health, with reduced risks of seizures and addiction to substances such as alcohol, cannabis, stimulants and opioids. People taking the weight-loss drugs also experienced decreased risks of suicidal ideation, self-harm, bulimia and psychotic disorders such as schizophrenia. The findings also showed a decreased risk of neurocognitive disorders such as Alzheimer’s and dementia.While GLP-1RA drugs display effectiveness against a wide array of health problems, the magnitude of associated benefits is modest — about a 10 percent to 20 percent reduction for most outcomes. The study also confirmed past research findings detailing the drugs’ potential to lower the risk of heart attack, stroke and other cardiovascular concerns.

Al-Aly emphasized that his study also highlighted potential downsides to the medications, including an increased risk of gastrointestinal problems such as nausea, vomiting, diarrhea, and in rare cases paralysis of the stomach. “These have been well documented in the research and anecdotally,” Al-Aly said. “Our study confirmed such findings.”

But the GLP-1RA drugs can negatively affect the pancreas and kidneys. While these adverse effects are uncommon, they can be very serious; physicians must be vigilant for signs of pancreatitis and monitor kidney function among people taking GLP-1RA medications. Kidney problems can occur without symptoms until the condition is at an advanced stage with limited treatment options.

“GLP-1RA drugs can have broad health benefits,” Al-Aly said. “However, they are not without risks. Our findings underscore the possibility for wider applications for these medications but also highlight important risks that should be carefully monitored in people taking these drugs.”

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Journal

Nature Medicine

DOI

10.1038/s41591-024-03412-w

Boosting physical fitness increases language comprehension in older adults

 

Increasing physical fitness levels does have a causal link with better language comprehension, according to the first study to show this effect.

 

The study published in Ageing, Neuropsychology and Cognition conducted by researchers from the University of Agder in Norway and University of Birmingham in the UK found that older monolingual adults who completed a six-month exercise programme were quicker at completing language comprehension tests compared to a control group.

 

The participants who followed a six-month home-based exercise programme were asked to do one circuit training session and two sessions of cardio intervals per week, either doing an uphill walk, a jog or run. Following the trial, the exercise groups for both monolingual and bilingual participants had significantly improved their fitness level, measured in VO2 max scores.

 

Participants in the study were tested pre and post exercise regime on their ability to recognise a target word in a spoken sentence. The monolingual participants who followed the exercise regime were 7% quicker at detecting the correct words after their fitness increased.

 

Dr Katrien Segaert from the School of Psychology at the University of Birmingham and an author of the study said:

 

“This is the first study we know of that establishes a causal link between improving fitness and language processing, particularly with older adults. Language processing is an important and interesting area of study: the ability to communicate is such a key function in everyone’s daily life. The results in the monolingual group show that increasing fitness is related to better cognition which underlines how important regular exercise is for healthy ageing.

 

“The exercise regime that participants followed was not complicated or demanding, and we saw that many of the participants were able to complete the programme by making simple adjustments to their daily routine, for example incorporating a brisk uphill walk into their day.

 

Among bilingual participants in the study, despite seeing increases in VO2 max scores for the exercise group, there was no relationship with improved scores in the language comprehension tests and the results were very similar to the control group. This was despite the test being conducted in the native language of the bilingual speaker.

 

Dr Eunice Fernandes from the Department of Foreign Languages and Translation at the University of Agder and corresponding author said:

 

“We did see different results in the bilingual group than in the monolingual group. This is very likely due to the different cognitive demands involved in language processing when adding a second language. It’s important to note that there was no detrimental impact of improving fitness among the bilingual group, and it underscores existing studies which show that there is something more complex going on in bilingual brains when it comes to language processing that wasn’t affected by this intervention.”

 

Intermittent fasting is effective for weight loss and improves cardiovascular health in people with obesity

 

A team of scientists led by the University of Granada (UGR), the Public University of Navarra (UPNA) and the CIBER has shown that intermittent fasting (reducing the number of hours of intake and extending the hours of fasting each day) is an effective method for losing weight and improves cardiovascular health in people with obesity problems.

Their work, published in the prestigious journal Nature Medicine, reveals that eating the last meal before 5pm and then not eating dinner at night is a safe and effective strategy for reducing subcutaneous abdominal fat, i.e. the fat just under the skin, especially after periods of excess such as Christmas.

In Spain, the prevalence of overweight and obesity reaches 70% in men and 50% in women, which is associated with multiple metabolic disorders such as type 2 diabetes and exponentially increases the risk of developing cardiovascular diseases, hypertension and certain types of cancer. This alarming weight gain in the population not only impacts people’s quality of life, but also represents a major challenge for the public health system. Scientific research is working hard to implement effective yet simple strategies to treat this problem, which is now considered a disease.

Calorie restriction diets help weight loss and improve cardiovascular health. However, they are not easy to maintain in the long term and often lead to most people eventually dropping out of treatment and thus regaining lost weight, or even gaining more than their starting weight.

Faced with the difficulties of maintaining adherence to traditional calorie restriction, new nutritional strategies are emerging. One of these is intermittent fasting, which consists of alternating periods of eating with periods of fasting ranging from hours to days. One type of intermittent fasting that has gained popularity in recent years is that which reduces the number of hours of intake and extends the hours of fasting each day. This is known as time-restricted eating. Normally, in Spain, people have their first breakfast at 7-8 a.m. and dinner at 21-22 p.m., so they have a 12-14 hour window of intake. In this type of intermittent fasting, the intake window is reduced from 12-14 hours to 6-8 hours, and people fast for 16-18 hours. This nutritional strategy helps to maintain a daily cycle of eating and fasting, which stabilises our body’s biological rhythms. We know that eating irregularly or at night disrupts these rhythms and increases the risk of obesity, cardiovascular disease and type 2 diabetes.

The research group PROFITH CTS-977 of the Department of Physical Education and Sports, Faculty of Sports Sciences and the Sport and Health University Research Institute (iMUDS) led by Dr. Jonatan Ruiz, in collaboration with ibs.Granada, the University Hospital Clínico San Cecilio and the University Hospital Virgen de las Nieves of Granada, as well as the research group led by Dr. Idoia Labayen of the University of Granada, in collaboration with Dr. Idoia Labayen of the University of Granada and the University Hospital Virgen de las Nieves of Granada. Idoia Labayen from the Public University of Navarra and the University Hospital of Navarra, together with the CIBER on Obesity (CIBEROBN) and the CIBER on Frailty and Healthy Ageing (CIBERFES) have investigated the effects of a 12-week intervention with three different fasting strategies: early fasting (intake sale: approximately 9:00-17:00), late fasting (approximately 14:00-22:00), and self-selected fasting, where people could select the time slot in which they wanted to eat, and did so on average between 12am and 8pm.

Study with 197 participants

In addition, all people participating in the study also received the standard treatment, which consisted of a nutrition education programme on Mediterranean diet and healthy lifestyles. In this randomised, controlled, multicentre trial, conducted in Granada (southern Spain) and Pamplona (northern Spain) and one of the largest to date, a total of 197 people (50% women) aged 30-60 years participated. Participants were randomly assigned to one of the following groups: treatment as usual (49 participants), early fasting (49 participants), late fasting (52 participants), or self-selected fasting (47 participants).

This study was part of the doctoral thesis of Manuel Dote-Montero, who is currently a postdoctoral fellow at the prestigious National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) in the United States.

Manuel Dote-Montero, together with Antonio Clavero Jimeno, a predoctoral researcher at the UGR, and Elisa Merchán Ramírez, a postdoctoral researcher at the UGR, led this study in Granada, and indicate that it is unclear whether the timing of the intake window – early, late or self-selected – may have a different effect on weight loss, visceral fat (i.e. fat surrounding organs in the abdominal area) or overall cardiovascular health in people who are overweight or obese.

The results of the study, published in the prestigious journal Nature Medicine, reveal that intermittent fasting showed no additional benefits over a nutrition education programme in reducing visceral fat. However, the fasting groups, regardless of the timing of intake, achieved greater weight loss, on average 3-4 kg, compared to the usual treatment group who continued with their intake window of at least 12 hours. Notably, the early fasting group reduced abdominal subcutaneous fat, i.e. the fat just under the skin, to a greater extent.

The study also assessed fasting and 24-hour glucose levels using a continuous glucose monitor worn by participants for 14 days before and at the end of the intervention. The results show that the early fasting group significantly improved fasting glucose levels and overnight glucose compared to the other groups.

Regulating glucose

These findings suggest that early fasting may be especially beneficial in optimising glucose regulation, which may help prevent diabetes and improve metabolic health. By not eating at night allows the body more time to digest and process nutrients, better regulation of blood glucose is facilitated, thus reducing the risk of developing sugar problems and other metabolic disorders, says Dr Labayen, principal investigator of the study in Pamplona and member of CIBEROBN together with Dr Jonatan Ruiz and Dr Manuel Muñoz (CIBERFES).

The researchers stress that all the fasting groups had a high adherence rate and no serious adverse events were recorded. Intermittent fasting is therefore presented as a safe and promising strategy for managing body weight and improving cardiovascular health in people who are overweight or obese. This information could be crucial for improving the efficacy of nutritional interventions in such populations.

Regular physical activity before cancer diagnosis may lower progression and death risks

 

Even relatively low levels of physical activity may be advantageous, findings show

Regular physical activity before a cancer diagnosis may lower the risks of both disease progression and death, suggests research published online in the British Journal of Sports Medicine.

And even relatively low levels of physical activity may be advantageous, the findings indicate.

There is compelling evidence that physical activity has a key part to play in lowering the risk of death from cancer, but the evidence isn’t as conclusive for its role in disease progression, explain the researchers.

To explore this further, they analysed anonymised data from the Discovery Health Medical Scheme (DHMS), linked to the Vitality health promotion programme. The DHMS is the largest open medical plan in South Africa, covering approximately 2.8 million beneficiaries.

All Vitality programme participants are rewarded for adopting healthy lifestyle behaviours, earning points for physical activity, recorded by activity trackers, logged gym attendance, or registered participation in organised fitness activities.

Activity type, frequency, duration and intensity are recorded and translated into weekly minutes of exercise.

In all, 28,248 Vitality programme members with stage 1 cancers, and comprehensive physical activity data for the year preceding diagnosis, were included in the study, which spanned the period 2007 to 2022.  

Breast and prostate cancers were the most common cancers, comprising 44% of the study total. 

The length of time between initial diagnosis and disease progression, death, or exit from the study ranged from 1 month to nearly 13 years. 

Cancer didn’t progress in nearly two thirds of the total sample (65.5%), but in just over a third (34.5%) it did. And while 81% survived, 19% died before the end of the study. The average time to death was 20 months and the average time to progression was 7 months. 

Levels of physical activity in the year before diagnosis were categorised as none recorded (17,457; 62% of participants); low, equal to 60 or fewer weekly minutes (3722;13%); and moderate to high, equal to 60 or more weekly minutes of moderate intensity physical activity (7069; 25%).

After accounting for potentially influential factors, including age at diagnosis, sex, economic and social position, and co-existing conditions, rates of cancer progression and death from any cause were lower among those who were physically active in the year preceding their diagnosis.

The odds of disease progression were 16% lower for those who had engaged in low levels of physical activity in the preceding year than among those who hadn’t recorded any physical activity, while the odds for those who had engaged in moderate to high levels were 27% lower.

Similarly, the odds of death from any cause were 33% lower among those who had engaged in low levels of physical activity compared with those who hadn’t recorded any, and 47% lower for those who had managed moderate to high levels.

Two years on from diagnosis, the likelihood of no disease progression among those with no recorded physical activity in the year before diagnosis was 74%, compared with 78% and 80%, respectively, for those achieving low and moderate to high levels of physical activity. 

While the likelihood of disease progression increased as time went on, it was still lower for those who had clocked up some level of physical activity in the year preceding their diagnosis.

After 3 years, the likelihood of no disease progression was 71%, 75%, and 78%, respectively, for none, low, and moderate to high levels of physical activity. And after 5 years, it was 66%, 70%, and 73%, respectively.

Similar patterns were evident for death from any cause. Two years after diagnosis, the probability of survival among those with no documented physical activity in the year preceding diagnosis was 91% compared with 94% and 95%, respectively, among those who had recorded low and moderate to high levels.

The equivalent probabilities of survival 3 years after diagnosis were 88%, 92%, and 94%, respectively, and 84%, 90%, and 91%, respectively, after 5 years. 

This is an observational study, and as such, can’t establish cause and effect. And the researchers acknowledge that they weren’t able to account for other potentially influential factors, such as smoking and alcohol consumption, while the data on weight (BMI) were incomplete.

But there are several plausible biological explanations for the findings, they suggest, chief among which is the way in which physical activity strengthens immunity by increasing numbers of natural killer cells, lymphocytes, neutrophils and eosinophils.

Physical activity may also lower the progression risk of hormone sensitive cancers, such as breast and prostate cancers, by regulating oestrogen and testosterone levels, they add.

“Physical activity may be considered to confer substantial benefits in terms of progression and overall mortality to those diagnosed with cancer,” they write. 

“In a world where cancer continues to be a significant public health burden, the promotion of physical activity can yield important benefits regarding the progression of cancer as well as its prevention and management,” they conclude.

Basking too long in a sauna without adequate hydration may risk heat stroke

Basking too long in a sauna may put bathers at risk of heat stroke, particularly if they haven’t drunk enough water beforehand, warn doctors in the journal BMJ Case Reports, after treating a woman whose condition required admission to hospital.

Although relatively rare, heat stroke can be life threatening, even in the absence of various underlying risk factors, such as heart, lung, or neurological disease, and heavy drinking or taking a cocktail of prescription meds, they point out.

Heat stroke is defined as a sharp increase in core body temperature above 40°C that is associated with acutely impaired brain function, and ‘non-exertional’ heat stroke results from prolonged exposure to high environmental temperatures, explain the authors.

They treated a woman in her early 70s who had been found unconscious in her local gym’s sauna, where she had been doing stretching exercises for around 45 minutes.

Her core body temperature was 42°C—normal temperature is 36.4°C—her blood pressure was extremely low, and her heart rate was extremely high. She had a seizure after her arrival in emergency care.

She had previously been diagnosed with type 1 diabetes and an underactive thyroid, but she wasn’t a smoker or heavy drinker, and was a regular gym goer, so had few risk factors, point out the authors.

She was rapidly cooled with wet towels and a fan and given intravenous fluids and blood products to stabilise her. 

Blood tests revealed malfunctioning kidneys and liver, evidence of a minor heart attack, and muscle tissue breakdown (rhabdomyolysis). 

She regained consciousness within 2 hours of reaching normal core temperature but was confused and drowsy for 2 days. By day 3 this had resolved and she had no further seizures during her inpatient stay, which lasted 12 days.

After 26 days she had more or less fully recovered, except for some mild fatigue and mild liver function disturbance.

This is just one case report after prolonged sauna use, and as far as the authors are aware, only 9 other similar cases have been reported. But 3 of those people died as a result.

“The prognosis of heat stroke varies according to patient factors, particularly extremes of age,” explain the authors. “Classical heat stroke in elderly people carries a mortality rate of  [more than] 50%, and this increases further with each additional organ dysfunction. 

“Heat-related deaths spike during heat waves, as has been observed in multiple large international datasets. Deaths from heat stroke are expected to rise as global temperatures continue to increase," they add.

“Once heat stroke has occurred, the key determinate of outcome is how rapidly a patient is cooled, as the time spent with elevated core body temperature is correlated to the degree of cellular damage,” they emphasise.

The woman in question comments: “My experience has emphasised the dangers of saunas and how important it is to be fully hydrated on entering a sauna, and for them to be regularly checked by staff. As a regular sauna user, I never suffered any issues and, on reflection, I believe I had not drunk enough water.”

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Morning coffee may protect the heart better than all-day coffee drinking

 People who drink coffee in the morning have a lower risk of dying from cardiovascular disease and a lower overall mortality risk compared to all-day coffee drinkers, according to research published in the European Heart Journal [1] today (Wednesday).

 

The research was led by Dr Lu Qi, HCA Regents Distinguished Chair and Professor at the Celia Scott Weatherhead School of Public Health and Tropical Medicine at Tulane University, New Orleans, USA. He said: “Research so far suggests that drinking coffee doesn’t raise the risk of cardiovascular disease, and it seems to lower the risk of some chronic diseases, such as type 2 diabetes. Given the effects that caffeine has on our bodies, we wanted to see if the time of day when you drink coffee has any impact on heart health.”

 

The study included 40,725 adults taking part in the US National Health and Nutrition Examination Survey (NHANES) between 1999 and 2018. As part of this study, participants were asked about all the food and drink they consumed on at least one day, including whether they drank coffee, how much and when. It also included a sub-group of 1,463 people who were asked to complete a detailed food and drink diary for a full week.

 

Researchers were able to link this information with records of deaths and cause of death over a period of nine to ten years.

 

Around 36% of people in the study were morning coffee drinkers (they primarily drank coffee before midday), 16% of people drank coffee throughout the day (morning, afternoon and evening) and 48% were not coffee drinkers.

 

Compared with people who did not drink coffee, morning coffee drinkers were 16% less likely to die of any cause and 31% less likely to die of cardiovascular disease. However, there was no reduction in risk for all-day coffee drinkers compared to non-coffee drinkers.

 

Morning coffee drinkers benefitted from the lower risks whether they were moderate drinkers (two to three cups) or heavy drinkers (more than three cups). Light morning drinkers (one cup or less) benefitted from a smaller decrease in risk.

 

Dr Qi said: “This is the first study testing coffee drinking timing patterns and health outcomes. Our findings indicate that it’s not just whether you drink coffee or how much you drink, but the time of day when you drink coffee that’s important. We don’t typically give advice about timing in our dietary guidance, but perhaps we should be thinking about this in the future.

 

“This study doesn’t tell us why drinking coffee in the morning reduces the risk of death from cardiovascular disease. A possible explanation is that consuming coffee in the afternoon or evening may disrupt circadian rhythms and levels of hormones such as melatonin. This, in turn, leads to changes in cardiovascular risk factors such as inflammation and blood pressure.

 

“Further studies are needed to validate our findings in other populations, and we need clinical trials to test the potential impact of changing the time of day when people drink coffee.”

 

In an accompanying editorial [2] Professor Thomas F. Lüscher from Royal Brompton and Harefield Hospitals, London, UK said: “In their study published in this issue of the European Heart Journal, Wang et al analysed the time of the day when coffee is consumed in 40 725 adults from the NHANES and of 1463 adults from the Women’s and Men’s Lifestyle Validation Study.

 

“During a median follow-up of almost a decade, and after adjustment for caffeinated and decaffeinated coffee intake, the amounts of cups per day, sleep hours, and other confounders, the morning-type, rather than the all-day-type pattern, was significantly associated with lower risks of all-cause mortality with a hazard ratio of 0.84 and of cardiovascular mortality of even 0.69 as compared with non-coffee drinkers.

 

“Why would time of the day matter? In the morning hours there is commonly a marked increase in sympathetic activity as we wake up and get out of bed, an effect that fades away during the day and reaches its lowest level during sleep. Thus, it is possible, as the authors point out, that coffee drinking in the afternoon or evening disrupts the circadian rhythm of sympathetic activity. Indeed, many all-day drinkers suffer from sleep disturbances. In this context, it is of interest that coffee seems to suppress melatonin, an important sleep-inducing mediator in the brain.

 

“Overall, we must accept the now substantial evidence that coffee drinking, particularly in the morning hours, is likely to be healthy. Thus, drink your coffee, but do so in the morning!”

Mediterranean diet changes gut bacteria, boosting memory and cognition

 

A new Tulane University study suggests the Mediterranean diet's brain-boosting benefits may work by changing the balance of bacteria in the gut.

In a study published in Gut Microbes Reports, researchers at Tulane University School of Medicine found that subjects following a Mediterranean diet developed distinctly different gut bacteria patterns compared to those eating a typical Western diet. These bacterial changes correlated with better memory and cognitive performance.

"We've known that what we eat affects brain function, but this study explores how that could be happening," said lead author Rebecca Solch-Ottaiano, PhD, neurology research instructor at Tulane’s Clinical Neuroscience Research Center. “Our findings suggest that dietary choices can influence cognitive performance by reshaping the gut microbiome."

The study found that rats fed a Mediterranean-style diet rich in olive oil, fish and fiber over 14 weeks showed increases in four beneficial types of gut bacteria and decreases in five others compared to rats eating a Western diet high in saturated fats. These bacterial changes were linked to improved performance on maze challenges designed to test memory and learning.

Specifically, higher levels of bacteria such as Candidatus Saccharimonas were associated with better cognitive performance, while increased levels of other bacteria, such as Bifidobacterium, correlated with poorer memory function.

The Mediterranean diet group also showed better cognitive flexibility — the ability to adapt to new information — and improved working memory compared to the Western diet group. They maintained lower levels of "bad" LDL cholesterol.

This study is the first to assess the effects of the Mediterranean on microbiota and cognitive function outcomes relative to the Western diet in a rodent model. The researchers used young rats approximately equivalent in age to 18-year-old humans to model the effects of diet during a critical developmental period. The diets were based on human consumption and used ingredients reflecting the complexity of human diets. The Mediterranean diet (MeDi) showed clear benefits for cognitive flexibility, memory, and gut health, suggesting potential parallels in young adults whose brains and bodies are still maturing.

“Our findings suggest that the Mediterranean diet or its biological effects could be harnessed to improve scholastic performance in adolescents, or work performance in young adults,” said corresponding author Dr. Demetrius M. Maraganore, Herbert J. Harvey, Jr. Chair of Neurosciences. “While these findings are based on animal models, they echo human studies linking the Mediterranean diet to improved memory and reduced dementia risk.”

The researchers emphasize that larger human studies are needed to confirm these effects and better understand the complex relationship between diet, gut bacteria, and brain function in young people.

For those interested in following a Mediterranean eating pattern, key components include:
- Olive oil as the primary fat source
- Abundant vegetables, fruits and whole grains
- Fish and lean proteins
- Limited red meat and saturated fats
- High fiber intake from various plant sources