Tag: 23/2/24

Categories : Cardiovascular DiseaseTags :

Common Hair Loss and Prostate Drug may also Cut Cardiovascular Risk

On By ModernMedia
Photo by Brett Sayles on Unsplash

The drug finasteride, also known as Propecia or Proscar, treats male pattern baldness and enlarged prostate in millions of men worldwide. But a new study published in the Journal of Lipid Research suggests that the drug may also possess a surprising, life-saving benefit: lowering cholesterol and reducing the overall risk of cardiovascular disease.

The study, led by University of Illinois Urbana-Champaign, found significant correlations between finasteride use and lower cholesterol levels in men taking part in the National Health and Nutrition Examination Survey between 2009 and 2016. In mice taking high finasteride doses, the researchers found reductions in total plasma cholesterol, delayed atherosclerosis progression, lower inflammation in the liver, and related benefits.

“When we looked at the men taking finasteride in the survey, their cholesterol levels averaged 30 points lower than men not taking the drug. I thought we’d see the opposite pattern, so it was very interesting,” said lead study author Jaume Amengual, assistant professor at U. of I.

As exciting as the survey results were, they had their limitations. Of nearly 4800 survey respondents meeting general health criteria for inclusion in the analysis, only 155, all men over 50, reported using finasteride. And the researchers couldn’t tell how much or how long men in the survey had taken the drug.

“This was not a clinical study in which you can control everything perfectly,” Amengual said. “It was more of an observation that led us to say, ‘Okay, now we’ve seen this in people. Let’s see what happens in mice.'”

But first, why would a hair loss and prostate drug affect cholesterol? Amengual studies atherosclerosis, the condition in which cholesterol plaques choke arteries, leading to stroke, heart attack, and other forms of cardiovascular disease. Because the disease is far more common in men than premenopausal women, scientists have long suspected the sex hormone testosterone is important in atherosclerosis, though its role isn’t entirely clear.

Finasteride works by blocking a protein found in hair follicles and the prostate gland that activates testosterone. The common thread, testosterone, was enough to pique Amengual’s interest.

“I was reading about this medication one day, and I started to notice that there were not many long-term studies of the implications of the drug. Initially, it was just my own curiosity, based on the fact that hormone levels are known to have an effect on atherosclerosis, hair loss, and prostate issues,” he said. “So, we decided to dig into it.”

After documenting the first-ever link, albeit observational, between finasteride and lower cholesterol in men, Amengual got doctoral student Donald Molina Chaves to see if the pattern held in mice.

Molina Chaves tested four levels of finasteride – 0, 10, 100, and 1000 mg/kg of food – in male mice genetically predisposed to atherosclerosis. The mice consumed the drug, along with a high-fat, high-cholesterol “Western” diet, for 12 weeks. After the experiment, Molina Chaves analysed the levels of cholesterol and other lipids in the mice, along with evidence of atherosclerotic plaques. He also tested gene expression in the liver, looked at bile acid metabolism, and analysed steroids, triglycerides, immune activity, and more.

“Mice that were given a high dose of finasteride showed lower cholesterol levels within the plasma as well as in the arteries,” Molina Chaves said. “There were also fewer lipids and inflammatory markers in the liver.”

Although the effects were only significant at the highest dose, a level Amengual calls outrageous for humans, he explains that mice metabolise finasteride differently than people.

“It’s an incredibly high level of the drug. But we use mice as a model, and they are extremely resistant to things that would kill any of us,” he said. “So it is not that crazy when you think about it that way.”

Humans take 1mg or 5mg doses of finasteride daily for hair loss and enlarged prostate, respectively. The fact that a clear pattern showed up in a survey of men likely taking one of these doses suggests the drug may be lowering cholesterol without the megadoses tested in mice.

The next step is for physicians to start tracking cholesterol in finasteride patients or conduct a clinical trial to verify the effect. Amengual says it may be especially important to understand how finasteride affects trans individuals.

“Over the past decade, doctors have started prescribing this drug for individuals transitioning either from male to female or female to male. In both cases, the hormonal changes can trigger hair loss,” he said. “The interesting thing is that transgender people are also at a higher risk of cardiovascular diseases. So this drug could have a potential beneficial effect to prevent cardiovascular disease not only in cis men, but also in transgender individuals.”

Finally, Amengual notes, like any medication, finasteride is not without risk. People should consult their doctors to learn more.

Source: University of Illinois College of Agricultural, Consumer and Environmental Sciences

Categories : Diet and NutritionTags :

Are Ultra-processed Foods the New ‘Silent Killer’?

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Photo by Patrick Fore on Unsplash

Nowadays, ultra-processed foods are packed with a bewildering range of additives: there are common ones like oil, fat, and sugar. There are also emulsifiers such as carrageenan, mono- and diglycerides, carboxymethylcellulose, polysorbate and soy lecithin. These continue to strip food of healthy nutrients while introducing other ingredients that could also be detrimental to human health.

Hundreds of novel ingredients never encountered by human physiology are now found in nearly 60% of the average adult’s diet and nearly 70% of children’s diets in the United States.

While obesity and lack of physical activity are well recognised contributors to avoidable morbidity and mortality, another emerging hazard is the unprecedented consumption of these ultra-processed foods in the standard American diet. This may be the new “silent” killer, as was unrecognised hypertension in previous decades.

Physicians from Florida Atlantic University’s Schmidt College of Medicine explored this hypothesis and provide important insights to health care providers in a battle where the entertainment industry, the food industry and public policy do not align with their patients’ needs. Their findings are published in a commentary in The American Journal of Medicine.

First generation of doctors to see a reduction in life expectancy

“Those of us practicing medicine in the US today find ourselves in an ignominious and unique position – we are the first cohort of health care professionals to have presided over a decline in life expectancy in 100 years,” said Dawn H. Sherling, MD, corresponding author, associate program director for the internal medicine residency and an associate professor of medicine, FAU Schmidt College of Medicine. “Our life expectancy is lower than other economically comparable countries. When we look at increasing rates of non-communicable diseases in less developed nations, we can see a tracking of this increase along with increasing consumption of ultra-processed foods in their diets.”

Although professional organizations such as the American College of Cardiology cautions patients to “choose minimally processed foods instead of ultra-processed foods” in their 2021 dietary guidelines, there is a caveat that “there is no commonly accepted definition for ultra-processed foods, and some healthy foods may exist within the ultra-processed food category.”

“When the components of a food are contained within a natural, whole food matrix, they are digested more slowly and more inefficiently, resulting in less calorie extraction, lower glycaemic loads in general, and lower rise in triglyceride-rich lipoproteins after eating, which could result in atherosclerotic plaque,” said Allison H. Ferris, MD, senior author, an associate professor and chair, Department of Medicine, and director of the internal medicine residency program, FAU Schmidt College of Medicine. “Therefore, even if the troublesome additives were removed from the ultra-processed food, there would still be concern for an over-consumption of these products possibly leading to obesity, diabetes and heart disease.”

The authors add that public health organisations are increasingly making use of the NOVA classification system, which divides foods into four categories – whole foods, culinary ingredients (items like butter, oil and salt), traditionally processed foods (such as bread and yogurt made with few ingredients), and ultra-processed foods – or those foods that are industrially made and use ingredients not normally found in a domestic kitchen.

According to the authors, one plausible mechanism to explain the hazards is that ultra-processed foods contain emulsifiers and other additives that the mammalian gastrointestinal tract mostly does not digest. They may act as a food source for our microbiota, and as such may be creating a dysbiotic microbiome that can, in the right host, promote disease.

“Additives, such as maltodextrin, may promote a mucous layer that is friendly to certain species of bacteria that are found in greater abundance in patients with inflammatory bowel disease,” said Sherling. “When the mucous layer is not properly maintained, the epithelial cell layer may become vulnerable to injury, as has been shown in feeding studies using carrageenan in humans and other studies in mice models, using polysorbate-80 and cellulose gum, triggering immunologic responses in the host.”

Food companies as powerful as the 20th century’s tobacco companies

The authors add that there have been marked increases in colorectal cancer in the US, especially among younger adults. They opine that increased ultra-processed food consumption may be a contributor as well as to several other gastrointestinal diseases.

“Whether ultra-processed foods contribute to our currently rising rates of non-communicable disease requires direct testing in analytic studies designed a priori to do so,” said Charles H. Hennekens, MD, FACPM, co-author, the First Sir Richard Doll Professor of Medicine and senior academic advisor, FAU Schmidt College of Medicine. “In the meantime, we believe it is incumbent upon all health care professionals to discuss the benefits of increasing consumption of whole foods and reducing consumption of ultra-processed foods with their patients.”

The authors also opine that just as the dangers of tobacco began to emerge during the middle of the prior century, decades passed before the preponderance of the evidence and the efforts of forward-thinking health officials prompted policy change to discourage the use of cigarettes. They say there is likely to be a similar path for ultra-processed foods.

“The multinational companies that produce ultra-processed foods are just as, if not more, powerful than tobacco companies were in the last century, and it is unlikely that governments will be able to move quickly on policies that will promote whole foods and discourage the consumption of ultra-processed foods,” said Sherling. “Importantly, health care providers also should remain cognizant of the difficulties that many of our patients have in being able to afford and find healthier options, which calls for a broader public health response.”

Source: Florida Atlantic University

Categories : Cardiovascular DiseaseTags :

High Levels of Niacin Linked to Cardiovascular Disease

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Photo by Robina Weermeijer on Unsplash

Cleveland Clinic researchers have identified a new pathway that contributes to cardiovascular disease associated with high levels of niacin, a common B vitamin previously recommended to lower cholesterol.

The team, led by Stanley Hazen, MD, PhD, reported in Nature Medicine that they had found a link between 4PY, a breakdown product from excess niacin, and cardiovascular disease. Higher circulating levels of 4PY were strongly associated with development of heart attack, stroke and other adverse cardiac events in large-scale clinical studies.

The researchers also showed in preclinical studies that 4PY directly triggers vascular inflammation which damages blood vessels and can lead to atherosclerosis over time. The study also details genetic links between 4PY and vascular inflammation.

The findings provide a foundation for potential new interventions and therapeutics to reduce or prevent that inflammation.

“What’s exciting about these results is that this pathway appears to be a previously unrecognised yet significant contributor to the development of cardiovascular disease,” said Dr Hazen, Chair of Cardiovascular and Metabolic Sciences at Cleveland Clinic’s Lerner Research Institute and Co-Section Head of Preventive Cardiology in the Heart, Vascular & Thoracic Institute.

“What’s more, we can measure it, meaning there is potential for diagnostic testing. These insights set the stage for developing new approaches to counteract the effects of this pathway.”

Niacin (vitamin B-3) is very common in a Western diet. “For decades, the United States and more than 50 nations have mandated niacin fortification in staple foods such as flour, cereals and oats to prevent disease related to nutritional deficiency,” said Dr Hazen.

Yet one in four subjects in the researchers’ patient cohorts appear to be getting too much, and had high levels of 4PY, which appears to contribute to cardiovascular disease development.

Dr. Hazen compares our intake of niacin as multiple taps pouring water into a bucket.

Once that bucket is filled, it begins to spill over. The human body then needs to process that spill-over and produce other metabolites, including 4PY.

“The main takeaway is not that we should cut out our entire intake of niacin – that’s not a realistic approach,” said Dr Hazen.

“Given these findings, a discussion over whether a continued mandate of flour and cereal fortification with niacin in the US could be warranted.”

Dr. Hazen notes broader use of over-the-counter supplements made with different forms of niacin have also become popular because of presumed anti-aging purposes.

He adds that patients should consult with their doctors before taking over-the-counter supplements and focus on a diet rich in fruit and vegetables while avoiding excess carbohydrates.

The new findings also might help explain why niacin, one of the first treatments prescribed to lower LDL cholesterol, is no longer a go-to treatment for for this.

Eventually niacin was shown to be less effective than other cholesterol-lowering drugs and was associated with other negative effects and higher mortality rates in previous research.

“Niacin’s effects have always been somewhat of a paradox,” Dr Hazen said.

“Despite niacin lowering of cholesterol, the clinical benefits have always been less than anticipated based on the degree of LDL reduction. This led to the idea that excess niacin caused unclear adverse effects that partially counteracted the benefits of LDL lowering. We believe our findings help explain this paradox. This illustrates why investigating residual cardiovascular risk is so critical; we learn so much more than what we set out to find.”

The study authors note that long-term investigations are needed to assess the effect of chronic elevation of 4PY levels on atherosclerosis and other phenotypes.

Source: Cleveland Clinic

Categories : Mental Health Obstetrics & GynaecologyTags :

Antidepressants Impact Prefrontal Cortex Development

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Photo by William Fortunato on Pexels

A new study published in Nature Communications suggests that use of antidepressants can impact early post-natal brain development, potentially contributing to the development of mental health disorders. The study, led by researchers at the University of Colorado Anschutz Medical Campus, focused on the effect of fluoxetine, commonly used in medications such as Prozac and Sarafem for treating depression and perinatal depression, on the developing prefrontal cortex of mice.

Since fluoxetine works by increasing the levels of serotonin in the brain, the researchers looked at the impact serotonin has on prefrontal cortex development.

“While it is known that serotonin plays a role in the brain development, the mechanisms responsible for this influence, specifically in the prefrontal cortex, have been unclear, ” said lead author Won Chan Oh, PhD, assistant professor in the Department of Pharmacology at CU Anschutz.

Changes in gestational and early postnatal serotonin levels can arise from many causes including maternal deprivation or abuse, diets high or low in tryptophan, or the use of medications such as selective serotonin reuptake inhibitors (SSRIs) that can readily cross the placenta or be passed to offspring through breast feeding. Disbalances of 5-HT during brain development are associated with increased risk of neurodevelopmental disorders such as autism spectrum disorder and long-lasting behavioural deficits, but the underlying mechanisms remain elusive.

Oh and his student, Roberto Ogelman, a neuroscience PhD candidate, found serotonin directly influences nascent and immature excitatory synaptic connections in the prefrontal cortex, which if disrupted or dysregulated during early development can contribute to various mental health disorders.

“Our research uncovers the specific processes at the synaptic level that explain how serotonin contributes to the development of this important brain region during early-life fluoxetine exposure,” adds Oh. “We are the first to provide experimental evidence of the direct impact of serotonin on the developing prefrontal cortex in mice.”

To study the effect, the researchers looked at the impact of deficiency and surplus of serotonin on brain development in mice. They discovered that serotonin is not just involved in overall brain function but also has a specific role in influencing how individual connections between neurons change and adapt, contributing to the brain’s ability to learn and adjust.

“Understanding this correlation has the potential to help with early intervention and the development of new therapeutics for neurodevelopmental disorders involving serotonin dysregulation,” said Oh.

The researchers plan to continue studying the impact of fluoxetine, next examining its impact on a developing brain later in life.

Source: Colorado University Anschutz Medical Campus