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MIND and Mediterranean diets associated with fewer Alzheimer's plaques and tangles

March 8, 2023

Science Daily/American Academy of Neurology

People who eat diets rich in green leafy vegetables as well as other vegetables, fruits, whole grains, olive oil, beans, nuts and fish may have fewer amyloid plaques and tau tangles in their brain -- signs of Alzheimer's disease -- than people who do not consume such diets, according to a study published in the March 8, 2023, online issue of Neurology®, the medical journal of the American Academy of Neurology.

The study examined how closely people followed the MIND and Mediterranean diets. While similar, the Mediterranean diet recommends vegetables, fruit, and three or more servings of fish per week while the MIND diet prioritizes green leafy vegetables like spinach, kale and collard greens along with other vegetables. The MIND diet also prioritizes berries over other fruit and recommends one or more servings of fish per week. Both the MIND and Mediterranean diet recommend small amounts of wine.

While this study shows an association of regularly consuming these diets with fewer Alzheimer's disease plaques and tangles, it does not establish a cause and effect relationship.

"These results are exciting -- improvement in people's diets in just one area -- such as eating more than six servings of green leafy vegetables per week, or not eating fried foods -- was associated with fewer amyloid plaques in the brain similar to being about four years younger," said study author Puja Agarwal, PhD, of RUSH University in Chicago. "While our research doesn't prove that a healthy diet resulted in fewer brain deposits of amyloid plaques, also known as an indicator of Alzheimer's disease, we know there is a relationship and following the MIND and Mediterranean diets may be one way that people can improve their brain health and protect cognition as they age."

The study involved 581 people with an average age of 84 at the time of diet assessment who agreed to donate their brains at death to advance research on dementia. Participants completed annual questionnaires asking how much they ate of food items in various categories.

The participants died an average of seven years after the start of the study. Right before death, 39% of participants had been diagnosed with dementia. When examined after death, 66% met the criteria for Alzheimer's disease.

At autopsy, researchers examined participants' brains to determine the amounts of amyloid plaques and tau tangles. Both are found in the brains of people with Alzheimer's disease but may also be found in the brains of older people with normal cognition. Researchers then looked back at the food questionnaires which were collected during follow-up and ranked the quality of diet for each person.

For the Mediterranean diet, there were 11 food categories. Participants were given a score of zero to 55, with higher scores if they adhered to the diet in these categories: whole grain cereals, fruits, vegetables, legumes, olive oil, fish and potatoes. They were given lower scores if they ate red meat, poultry and full-fat dairy products.

For the MIND diet, there were 15 categories. Participants were given a score of zero to 15, with one point each for 10 brain-healthy food groups including green leafy vegetables, other vegetables, nuts, berries, beans, whole grains, fish, poultry, olive oil, and wine. They lost a point if they ate foods more than recommended in five unhealthy food groups, including red meats, butter and margarine, cheese, pastries and sweets, and fried and fast food.

Researchers then divided participants into three groups for each diet and compared those in the highest groups to those in the lowest groups. For the Mediterranean diet, people in the highest group had an average score of 35 while those in the lowest group had an average score of 26. For the MIND diet, the highest group had an average score of 9 while the lowest group had an average score of 6.

After adjusting for age at death, sex, education, total calorie intake and whether people had a gene linked to a greater risk of Alzheimer's disease, researchers found people who scored highest for adhering to the Mediterranean diet had average plaque and tangle amounts in their brains similar to being 18 years younger than people who scored lowest. Researchers also found people who scored highest for adhering to the MIND diet had average plaque and tangle amounts similar to being 12 years younger than those who scored lowest.

A MIND diet score one point higher corresponded to typical plaque amounts of participants who were 4.25 years younger in age.

When looking at single diet components, researchers found people who ate the highest amounts of green leafy vegetables, or seven or more servings per week, had plaque amounts in their brains corresponding to being almost 19 years younger than people who ate the fewest, with one or fewer servings per week.

"Our finding that eating more green leafy vegetables is in itself associated with fewer signs of Alzheimer's disease in the brain is intriguing enough for people to consider adding more of these vegetables to their diet," said Agarwal. "Future studies are needed to establish our findings further."

A limitation of the study was that participants were mostly white, non-Hispanic, and older so the results cannot be generalized to other populations.

https://www.sciencedaily.com/releases/2023/03/230308201051.htm

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A good night's sleep may make it easier to stick to exercise and diet goals

March 3, 2023

Science Daily/American Heart Association

People who reported getting regular, uninterrupted sleep did a better job sticking to their exercise and diet plans while trying to lose weight, according to preliminary research presented at the American Heart Association's Epidemiology, Prevention, Lifestyle & Cardiometabolic Health Scientific Sessions 2023. The meeting will be held in Boston, February 28-March 3, 2023, and offers the latest science on population-based health and wellness and implications for lifestyle and cardiometabolic health.

"Focusing on obtaining good sleep -- seven to nine hours at night with a regular wake time along with waking refreshed and being alert throughout the day -- may be an important behavior that helps people stick with their physical activity and dietary modification goals," said Christopher E. Kline, Ph.D., an associate professor in the department of health and human development at the University of Pittsburgh. "A previous study of ours reported that better sleep health was associated with a significantly greater loss of body weight and fat among participants in a year-long, behavioral weight loss program."

The researchers examined whether good sleep health was related to how well people adhered to the various lifestyle modifications prescribed in a 12-month weight loss program. The weight-loss program included 125 adults (average age of 50 years, 91% female, 81% white) who met criteria for overweight or obesity (body mass index of 27-44) without any medical conditions requiring medical supervision of their diet or physical activity.

Sleep habits were measured at the beginning of the program, at 6 months and at 12 months, through patient questionnaires, a sleep diary and 7-day readings from a wrist-worn device that recorded sleep, waking activity and rest. These measures were used to score each participant as "good" or "poor" on six measures of sleep: regularity; satisfaction; alertness; timing; efficiency (the percentage of time spent in bed when actually asleep); and duration. A composite sleep health score of 0-6 was calculated for each participant, with one point for each "good" measure of sleep health, with higher scores indicating better levels of sleep health.

Adherence to the weight loss program was measured by percentage of group intervention sessions attended; percentage of days in which each participant ate between 85-115% of their recommended daily calories; and change in daily duration of moderate or vigorous physical activity. Participants had an average sleep health score of 4.5 out of 6 at the start of the study, at 6 months and at 12 months. Participants self-reported their caloric intake each day using a phone app and researchers measured participants' physical activity with an accelerometer worn at the waist for one week at a time at the start of the study, at 6 months and at 12 months.

After adjusting the sleep health scores for age, gender, race and whether or not there was a partner sharing the bed, the researchers found that better sleep health was associated with higher rates of attendance at group interval sessions, adherence to caloric intake goals and improvement in time spent performing moderate-vigorous physical activity. They found:

  • Participants attended 79% of group sessions in the first six months and 62% of group sessions in the second six months.

  • Participants met their daily caloric intake goals on 36% of days in the first six months and 21% in the second six months.

  • Participants increased their total daily time spent in moderate-vigorous activity by 8.7 minutes in the first six months, however, their total time spent decreased by 3.7 minutes in the second six months.

The decrease in group session attendance, caloric intake and in time spent in moderate-vigorous activity in the second six months was expected, Kline said. "As one continues in a long-term behavioral weight loss intervention, it's normal for the adherence to weight loss behaviors to decrease," he said.

Additionally, while there was an association between better sleep health scores and an increase in physical activity, it was not strong enough to be statistically significant, meaning that researchers cannot rule out that the results were due to chance.

"We had hypothesized that sleep would be associated with lifestyle modification; however, we didn't expect to see an association between sleep health and all three of our measures of lifestyle modification," he said. "Although we did not intervene on sleep health in this study, these results suggest that optimizing sleep may lead to better lifestyle modification adherence. "

The study's limitations include that it did not incorporate any intervention to help participants improve their sleep, that the study sample was not recruited based upon participants' sleep health characteristics, and that the overall sample population had relatively good sleep health at baseline. The sample was also primarily white and female, so it is unclear whether these results are generalizable to more diverse populations.

"One question of interest for future research is whether we can increase adherence to lifestyle modifications -- and, ultimately, increase weight loss -- if we improve a person's sleep health," Kline said.

A second question for the researchers is how such an intervention would be timed to improve sleep.

"It remains unclear whether it would be best to optimize sleep prior to rather than during attempted weight loss. In other words, should clinicians tell their patients to focus on getting better and more regular sleep before they begin to attempt weight loss, or should they try to improve their sleep while at the same time modifying their diet and activity levels?" Kline said.

Improving one's sleep health is something everyone can do to improve their cardiovascular health and is a key component of the American Heart Association's Life's Essential 8. Sleep was added in 2022 as the eighth component of optimal cardiovascular health, which includes eating healthy food, being physically active, not smoking, getting enough sleep, maintaining a healthy weight and controlling cholesterol, blood sugar and blood pressure levels. Cardiovascular disease claims more lives each year in the U.S. than all forms of cancer and chronic lower respiratory disease combined, according to the 2023 Statistical Update from the American Heart Association.

"There are over 100 studies linking sleep to weight gain and obesity, but this was a great example showing how sleep isn't just tied to weight itself, it's tied to the things we're doing to help manage our own weight. This could be because sleep impacts the things that drive hunger and cravings, your metabolism and your ability to regulate metabolism and the ability to make healthy choices in general," said Michael A. Grandner, Ph.D., MTR. Grandner is director of the Sleep and Heath Research Program at the University of Arizona, director of the Behavioral Sleep Medicine Clinic at the Banner-University Medical Center in Tucson, Arizona, and was a co-author of the Association's Life's Essential 8 cardiovascular health score. "Studies like this really go to show that all of these things are connected, and sometimes sleep is the thing that we can start taking control over that can help open doors to other avenues of health."

https://www.sciencedaily.com/releases/2023/03/230303175844.htm

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Taking vitamin D could help prevent dementia

Taking vitamin D supplements may help ward off dementia, according to a new, large-scale study.

March 1, 2023

Science Daily/University of Exeter

Taking vitamin D supplements may help ward off dementia, according to a new, large-scale study.

Researchers at the University of Calgary's Hotchkiss Brain Institute in Canada and the University of Exeter in the UK explored the relationship between vitamin D supplementation and dementia in more than 12,388 participants of the US National Alzheimer's Coordinating Center, who had a mean age of 71 and were dementia-free when they signed up. Of the group, 37 per cent (4,637) took vitamin D supplements.

In the study, published in Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring, the team found that taking vitamin D was associated with living dementia-free for longer, and they also found 40 per cent fewer dementia diagnoses in the group who took supplements.

Across the entire sample, 2,696 participants progressed to dementia over ten years; amongst them, 2,017 (75%) had no exposure to vitamin D throughout all visits prior to dementia diagnosis, and 679 (25%) had baseline exposure.

Professor Zahinoor Ismail, of the University of Calgary and University of Exeter, who led the research, said: "We know that vitamin D has some effects in the brain that could have implications for reducing dementia, however so far, research has yielded conflicting results. Our findings give key insights into groups who might be specifically targeted for vitamin D supplementation. Overall, we found evidence to suggest that earlier supplementation might be particularly beneficial, before the onset of cognitive decline."

While Vitamin D was effective in all groups, the team found that effects were significantly greater in females, compared to males. Similarly, effects were greater in people with normal cognition, compared to those who reported signs of mild cognitive impairment -- changes to cognition which have been linked to a higher risk of dementia.

The effects of vitamin D were also significantly greater in people who did not carry the APOEe4 gene, known to present a higher risk for Alzheimer's dementia, compared to non-carriers. The authors suggest that people who carry the APOEe4 gene absorb vitamin D better from their intestine, which might reduce the vitamin D supplementation effect. However, no blood levels were drawn to test this hypothesis.

Previous research has found that low levels of vitamin D are linked to higher dementia risk. Vitamin D is involved in the clearance of amyloid in the brain, the accumulation of which is one of the hallmarks of Alzheimer's disease. Studies have also found that vitamin D may provide help to protect the brain against build-up of tau, another protein involved in the development of dementia.

Co-author Dr Byron Creese, at the University of Exeter, said: "Preventing dementia or even delaying its onset is vitally important given the growing numbers of people affected. The link with vitamin D in this study suggests that taking vitamin D supplements may be beneficial in preventing or delaying dementia, but we now need clinical trials to confirm whether this is really the case. The ongoing VitaMIND study at the University of Exeter is exploring this issue further by randomly assigning participants to either take vitamin D or placebo and examining changes in memory and thinking tests over time."

The VitaMIND study is run via PROTECT, an online study open to people aged 40 and over. In PROTECT annual questionnaires on detailed lifestyle factors combine with cognitive testing, to determine what keeps the brain sharp in later life. To find out more or to sign up, visit their website. In Canada, CAN-PROTECT, is a linked online study on aging, in people aged 40 and over, with an additional focus on caregiving in dementia.

https://www.sciencedaily.com/releases/2023/03/230301101511.htm

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Fructose could drive Alzheimer's disease

An evolutionary foraging instinct that relied on the sugar fructose, may now be fueling the formation of Alzheimer's disease

February 13, 2023

Science Daily/University of Colorado Anschutz Medical Campus

An ancient human foraging instinct, fueled by fructose production in the brain, may hold clues to the development and possible treatment of Alzheimer's disease (AD), according to researchers at the University of Colorado Anschutz Medical Campus.

The study, published recently in The American Journal of Clinical Nutrition, offers a new way of looking at a fatal disease characterized by abnormal accumulations of proteins in the brain that slowly erode memory and cognition.

"We make the case that Alzheimer's disease is driven by diet," said the study's lead author Richard Johnson, MD, professor at the University of Colorado School of Medicine specializing in renal disease and hypertension. The study co-authors include Maria Nagel, MD, research professor of neurology at the CU School of Medicine.

Johnson and his team suggest that AD is a harmful adaptation of an evolutionary survival pathway used in animals and our distant ancestors during times of scarcity.

"A basic tenet of life is to assure enough food, water and oxygen for survival," the study said. "Much attention has focused on the acute survival responses to hypoxia and starvation. However, nature has developed a clever way to protect animals before the crisis actually occurs."

When threatened with the possibility of starvation, early humans developed a survival response which sent them foraging for food. Yet foraging is only effective if metabolism is inhibited in various parts of the brain. Foraging requires focus, rapid assessment, impulsivity, exploratory behavior and risk taking. It is enhanced by blocking whatever gets in the way, like recent memories and attention to time. Fructose, a kind of sugar, helps damp down these centers, allowing more focus on food gathering.

In fact, the researchers found the entire foraging response was set in motion by the metabolism of fructose whether it was eaten or produced in the body. Metabolizing fructose and its byproduct, intracellular uric acid, was critical to the survival of both humans and animals.

The researchers noted that fructose reduces blood flow to the brain's cerebral cortex involved in self-control, as well as the hippocampus and thalamus. Meanwhile, blood flow increased around the visual cortex associated with food reward. All of this stimulated the foraging response.

"We believe that initially the fructose-dependent reduction in cerebral metabolism in these regions was reversible and meant to be beneficial," Johnson said. "But chronic and persistent reduction in cerebral metabolism driven by recurrent fructose metabolism leads to progressive brain atrophy and neuron loss with all of the features of AD."

Johnson suspects the survival response, what he calls the `survival switch,' that helped ancient humans get through periods of scarcity, is now stuck in the `on' position in a time of relative abundance. This leads to the overeating of high fat, sugary and salty food prompting excess fructose production.

Fructose produced in the brain can lead to inflammation and ultimately Alzheimer's disease, the study said. Animals given fructose show memory lapses, a loss in the ability to navigate a maze and inflammation of the neurons.

"A study found that if you keep laboratory rats on fructose long enough they get tau and amyloid beta proteins in the brain, the same proteins seen in Alzheimer's disease," Johnson said. "You can find high fructose levels in the brains of people with Alzheimer's as well."

Johnson suspects that the tendency of some AD patients to wander off might be a vestige of the ancient foraging response.

The study said more research is needed on the role of fructose and uric acid metabolism in AD.

"We suggest that both dietary and pharmacologic trials to reduce fructose exposure or block fructose metabolism should be performed to determine if there is potential benefit in the prevention, management or treatment of this disease," Johnson said.

https://www.sciencedaily.com/releases/2023/02/230213113345.htm

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Mushrooms magnify memory by boosting nerve growth

February 10, 2023

Science Daily/University of Queensland

Researchers from The University of Queensland have discovered the active compound from an edible mushroom that boosts nerve growth and enhances memory.

Professor Frederic Meunier from the Queensland Brain Institute said the team had identified new active compounds from the mushroom, Hericium erinaceus.

Researchers have discovered lion's mane mushrooms improve brain cell growth and memory in pre-clinical trials. 

"Extracts from these so-called 'lion's mane' mushrooms have been used in traditional medicine in Asian countries for centuries, but we wanted to scientifically determine their potential effect on brain cells," Professor Meunier said.

"Pre-clinical testing found the lion's mane mushroom had a significant impact on the growth of brain cells and improving memory.

"Laboratory tests measured the neurotrophic effects of compounds isolated from Hericium erinaceus on cultured brain cells, and surprisingly we found that the active compounds promote neuron projections, extending and connecting to other neurons.

"Using super-resolution microscopy, we found the mushroom extract and its active components largely increase the size of growth cones, which are particularly important for brain cells to sense their environment and establish new connections with other neurons in the brain."

Co-author, UQ's Dr Ramon Martinez-Marmol said the discovery had applications that could treat and protect against neurodegenerative cognitive disorders such as Alzheimer's disease.

"Our idea was to identify bioactive compounds from natural sources that could reach the brain and regulate the growth of neurons, resulting in improved memory formation," Dr Martinez-Marmol said.

Dr Dae Hee Lee from CNGBio Co, which has supported and collaborated on the research project, said the properties of lion's mane mushrooms had been used to treat ailments and maintain health in traditional Chinese medicine since antiquity.

"This important research is unravelling the molecular mechanism of lion's mane mushroom compounds and their effects on brain function, particularly memory," Dr Lee said.

https://www.sciencedaily.com/releases/2023/02/230210115544.htm

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Why a high fat diet could reduce the brain's ability to regulate food intake

January 26, 2023

Science Daily/The Physiological Society

Regularly eating a high fat/calorie diet could reduce the brain’s ability to regulate calorie intake. New research in rats published in The Journal of Physiologyfound that after short periods of being fed a high fat/high calorie diet, the brain adapts to react to what is being ingested and reduces the amount of food eaten to balance calorie intake. The researchers from Penn State College of Medicine, US, suggest that calorie intake is regulated in the short-term by cells called astrocytes (large star-shaped cells in the brain that regulate many different functions of neurons in the brain) that control the signalling pathway between the brain and the gut. Continuously eating a high fat/calorie diet seems to disrupt this signalling pathway.

Understanding the brain’s role and the complex mechanisms that lead to overeating, a behaviour that can lead to weight gain and obesity, could help develop therapies to treat it. Obesity is a global public-health concern because it is associated with increased risk of cardiovascular diseases and type 2 diabetes. In England, 63% of adults are considered above a healthy weight and around half of these are living with obesity. One in three children leaving primary school are overweight or obese1.

Dr Kirsteen Browning, Penn State College of Medicine, US, said,

“Calorie intake seems to be regulated in the short-term by astrocytes. We found that a brief exposure (three to five days) of high fat/calorie diet has the greatest effect on astrocytes, triggering the normal signalling pathway to control the stomach. Over time, astrocytes seem to desensitise to the high fat food. Around 10-14 days of eating high fat/calorie diet, astrocytes seem to fail to react and the brain’s ability to regulate calorie intake seems to be lost. This disrupts the signalling to the stomach and delays how it empties.”

Astrocytes initially react when high fat/calorie food is ingested. Their activation triggers the release of gliotransmitters, chemicals (including glutamate and ATP) that excite nerve cells and enable normal signalling pathways to stimulate neurons that control how the stomach works. This ensures the stomach contracts correctly to fill and empty in response to food passing through the digestive system. When astrocytes are inhibited, the cascade is disrupted. The decrease in signalling chemicals leads to a delay in digestion because the stomach doesn’t fill and empty appropriately.

The vigorous investigation used behavioural observation to monitor food intake in rats (N=205, 133 males, 72 females) which were fed a control or high fat/calorie diet for one, three, five or 14 days. This was combined with pharmacological and specialist genetic approaches (both in vivo and in vitro) to target distinct neural circuits. Enabling the researchers to specifically inhibit astrocytes in a particular region of the brainstem (the posterior part of the brain that connects the brain to the spinal cord), so they could assess how individual neurons behaved to studying rats' behaviour when awake.

Human studies will need to be carried out to confirm if the same mechanism occurs in humans. If this is the case, further testing will be required to assess if the mechanism could be safely targeted without disrupting other neural pathways.

The researchers have plans to further explore the mechanism. Dr Kirsteen Browning said,

“We have yet to find out whether the loss of astrocyte activity and the signalling mechanism is the cause of overeating or that it occurs in response to the overeating. We are eager to find out whether it is possible to reactivate the brain’s apparent lost ability to regulate calorie intake. If this is the case, it could lead to interventions to help restore calorie regulation in humans.”

https://www.sciencedaily.com/releases/2023/01/230126100217.htm

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Loneliness associated with unhealthful diets and physical inactivity among US college students

January 20, 2023

Science Daily/George Mason University

Transitioning to a new environment, as many college freshman do, can increase feelings of loneliness, and feelings of loneliness in college students have dramatically increased in the last decade, according to the National College Health Assessment. Additionally, a 2021 survey reported that 44% of U.S. college students described their weight as more than normal, i.e. either in the overweight or obese category. Though loneliness has been linked to unhealthy weight and physical inactivity, there is a lack of research on dietary behaviors in college students and the role it can play in obesity in college students.

With data from the Mason: Health Starts Here cohort study, Master of Nutrition alum Li Jiang found that loneliness was related to altered diet quality and physical inactivity. The research was done as part of Jiang's master's thesis, and Mason Nutrition and Food Studies Department Chair Lawrence J. Cheskin, Associate Professor Lilian de Jonge, former faculty member Cara Frankenfeld, and former postdoctoral fellow Ziaul H. Rana also contributed to the project.

"Our study supports a potential need for further research in understanding unhealthful dietary behavior and physical activity which may be related to loneliness, an emotion that impacts many college students," says Jiang.

Sedentary (19.2%) and low active (53.8%) behaviors were more frequent in students reporting high loneliness (score ranges of 4-6 and 7-9) than those reporting low loneliness (score of 10-12). Students reporting more loneliness had higher fat diets than students reporting less loneliness.

"Interventions to reduce loneliness may have a positive effect on health promotion in this population. This data go along with other initial findings from the Health Starts Here study that college students are not meeting healthy dietary guidelines or getting enough physical activity," said Cheskin, who has an MD.

The study is a cross-sectional study that analyzed baseline data collected in the first wave of Mason: Health Start Here in 2019, and was funded by George Mason University's Institute for BioHealth Innovation.

"Loneliness is associated with unhealthful dietary behaviors and physical inactivity among US college students," was published in November 2022 in the Journal of American College Health.

Mason: Health Starts Here is a first-of-its-kind transdisciplinary student cohort study to understand and improve the health and well-being of university students. This research will follow a broad sample of young adults, specifically Mason students, over time to capture the diversity of their experiences in college and how it affects their health and well-being.

https://www.sciencedaily.com/releases/2023/01/230120131311.htm

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Vitamin D benefits and metabolism may depend on body weight

People with higher body mass index had a blunted response to vitamin D supplementation, explaining observed differences in outcomes such as cancer, diabetes, and autoimmune disease

January 17, 2023

Science Daily/Brigham and Women's Hospital

Researchers from Brigham and Women's Hospital, a founding member of the Mass General Brigham healthcare system, have found new evidence that vitamin D may be metabolized differently in people with an elevated body mass index (BMI). The study, appearing in JAMA Network Open, is a new analysis of data from the VITAL trial, a large nationwide clinical trial led by Brigham researchers that investigated whether taking vitamin D or marine omega-3 supplements could reduce the risk of developing cancer, heart disease, or stroke.

"The analysis of the original VITAL data found that vitamin D supplementation correlated with positive effects on several health outcomes, but only among people with a BMI under 25," said first author Deirdre K. Tobias, ScD, an associate epidemiologist in Brigham's Division of Preventive Medicine. "There seems to be something different happening with vitamin D metabolism at higher body weights, and this study may help explain diminished outcomes of supplementation for individuals with an elevated BMI."

Vitamin D is an essential nutrient involved in many biological processes, most notably helping our body absorb minerals, such as calcium and magnesium. While some of the vitamin D we need is made in the body from sunlight, vitamin D deficiencies are often treated with supplementation. Evidence from laboratory studies, epidemiologic research and clinical research has also suggested that vitamin D may play a role in the incidence and progression of cancer and cardiovascular disease, and it was this evidence that prompted the original VITAL trial.

The VITAL trial was a randomized, double-blind, placebo-controlled trial in 25,871 U.S. participants, which included men over the age of 50 and women over the age of 55. All participants were free of cancer and cardiovascular disease at the time of enrollment. While the trial found little benefit of vitamin D supplementation for preventing cancer, heart attack, or stroke in the overall cohort, there was a statistical correlation between BMI and cancer incidence, cancer mortality, and autoimmune disease incidence. Other studies suggest similar results for type 2 diabetes.

The new study aimed to investigate this correlation. The researchers analyzed data from 16,515 participants from the original trial who provided blood samples at baseline (before randomization to vitamin D), as well as 2,742 with a follow-up blood sample taken after two years. The researchers measured the levels of total and free vitamin D, as well as many other novel biomarkers for vitamin D, such as its metabolites, calcium, and parathyroid hormone, which helps the body utilize vitamin D.

"Most studies like this focus on the total vitamin D blood level," said senior author JoAnn E. Manson, MD, DrPH, chief of the Division of Preventive Medicine at the Brigham and principal investigator of VITAL. "The fact that we were able to look at this expanded profile of vitamin D metabolites and novel biomarkers gave us unique insights into vitamin D availability and activity, and whether vitamin D metabolism might be disrupted in some people but not in others."

The researchers found that vitamin D supplementation increased most of the biomarkers associated with vitamin D metabolism in people, regardless of their weight. However, these increases were significantly smaller in people with elevated BMIs.

"We observed striking differences after two years, indicating a blunted response to vitamin D supplementation with higher BMI," Tobias said. "This may have implications clinically and potentially explain some of the observed differences in the effectiveness of vitamin D supplementation by obesity status."

"This study sheds light on why we're seeing 30-40 percent reductions in cancer deaths, autoimmune diseases, and other outcomes with vitamin D supplementation among those with lower BMIs but minimal benefit in those with higher BMIs, suggesting it may be possible to achieve benefits across the population with more personalized dosing of vitamin D," said Manson. "These nuances make it clear that there's more to the vitamin D story."

The authors conclude that the VITAL findings are a call to action for the research community to continue exploring the potential benefits of vitamin D supplementation for preventing cancer and other diseases and to take BMI into account when evaluating the supplement's health impacts.

https://www.sciencedaily.com/releases/2023/01/230117110511.htm

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Obesity linked to macular degeneration

January 10, 2023

Science Daily/University of Montreal

A Canadian study published in the journal Scienceelucidates a new molecular mechanism that may cause age-related macular degeneration (AMD).

The research at Hôpital Maisonneuve-Rosement, in Montreal, shows how life stressors such as obesity reprogram immune system cells and make them destructive to the eye as it ages.

"We wanted to know why some people with a genetic predisposition develop AMD while others are spared," said Université de Montréal ophtalmology professor Przemyslaw (Mike) Sapieha, who led the study by his postdoctoral fellow Dr. Masayuki Hata.

"Although considerable effort has been invested in understanding the genes responsible for AMD, variations and mutations in susceptibility genes only increase the risk of developing the disease, but do not cause it," Sapieha explained.

"This observation suggests that we must gain a better understanding of how other factors such as environment and lifestyle contribute to disease development."

AMD is a major cause of irreversible blindness worldwide and affected approximately 196 million people in 2020. It comes in two forms:

  • dry AMD, characterized by the accumulation of fatty deposits at the back of the eye and the death of nerve cells in the eye,

  • and wet AMD, which is characterized by diseased blood vessels that develop in the most sensitive part of the sight-generating tissue, called the macula.

Contact with pathogens

It is already known that the immune system in the eye of a person with AMD becomes dysregulated and aggressive. Normally, immune cells keep the eye healthy, but contact with pathogens such as bacteria and viruses can make them go awry.

At the same time, immune cells are also activated when the body is exposed to stressors such as excess fat in obesity, making being overweight the number one non-genetic risk factor for developing AMD, after smoking.

In their study, Sapieha and Hata used obesity as a model to accelerate and exaggerate the stressors experienced by the body throughout life.

They found that transient obesity or a history of obesity leads to persistent changes in the DNA architecture within immune cells, making them more susceptible to producing inflammatory molecules.

"Our findings provide important information about the biology of the immune cells that cause AMD and will allow for the development of more tailored treatments in the future," said Hata, now an ophthalmology professor at Kyoto University, in Japan.

The researchers hope their discovery will lead other scientists to broaden their interest beyond obesity-related diseases to other diseases characterized by increased neuroinflammation, including Alzheimer's disease and multiple sclerosis.

https://www.sciencedaily.com/releases/2023/01/230110191415.htm

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Patterns of lifespan weight gain/loss may predict dementia risk

Monitoring risk indicators such as weight patterns offer opportunities for early intervention

December 15, 2022

Science Daily/Boston University School of Medicine

Dementia is a growing global public health concern currently affecting 50 million people and is expected to rise dramatically to more than 150 million cases worldwide by 2050. Obesity, commonly measured by body mass index (BMI), continues to be a global epidemic and earlier studies suggested that obesity at midlife may lead to increased risk for dementia. But the association between BMI and the risk of dementia remains unclear.

Now, researchers from Boston University Chobanian & Avedisian School of Medicine and Chinese Academy of Medical Sciences & Peking Union Medical College, have found that different patterns of BMI changes over one's life course may be an indicator of a person's risk for dementia.

"These findings are important because previous studies that looked at weight trajectories didn't consider how patterns of weight gain/stability/loss might help signal that dementia is potentially imminent," explained corresponding author Rhoda Au, PhD, professor of anatomy and neurobiology.

Through the Framingham Heart Study, a group of participants was followed for 39 years and their weight was measured approximately every 2-4 years. The researchers compared different weight patterns (stable, gain, loss) among those who did and did not become demented.

They found the overall trend of declining BMI was associated with a higher risk of developing dementia. However, after further exploration, they found a subgroup with a pattern of initial increasing BMI followed by declining BMI, both occurring within midlife, which appeared to be central to the declining BMI-dementia association.

Au points out that for individuals, family members, and primary care physicians, it is relatively easy to monitor weight. "If after a steady increase in weight that is common as one gets older, there is an unexpected shift to losing weight post midlife, it might be good to consult with one's healthcare provider and pinpoint why. There are some potential treatments emerging where early detection might be critical in the effectiveness of any of these treatments as they are approved and become available," she adds.

The researchers hope this study will illustrate that the seeds for dementia risk are being sowed across many years, likely even across the entire lifespan. "Dementia is not necessarily inevitable and monitoring risk indicators such as something as easy to notice as weight patterns, might offer opportunities for early intervention that can change the trajectory of disease onset and progression."

https://www.sciencedaily.com/releases/2022/12/221215104559.htm

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