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New Cholesterol Guidelines Could Drastically Reduce Statin Use for Millions

By University of Pittsburgh June 16, 2024

A recent study indicates that if national guidelines adopt the new PREVENT equations, about 40% fewer U.S. adults might be recommended statins for heart disease prevention, decreasing from 45.4 million to 28.3 million individuals. This study, which utilized recent and diverse data, suggests a need for targeted cholesterol management in higher-risk populations and careful communication with patients who may no longer meet statin criteria under these updated guidelines.

Adopting new PREVENT equations could lead to a significant reduction in statin recommendations, impacting 40% of currently eligible U.S. adults, and highlights the importance of precise risk assessment and patient communication in cholesterol management.

If national guidelines were updated to include a new risk equation, approximately 40% fewer individuals may qualify for cholesterol-lowering statins to prevent heart disease, suggests a study involving researchers from the University of Pittsburgh , Beth Israel Deaconess Medical Center , and University of Michigan . The research, published in JAMA Internal Medicine , explores the implications of broadly implementing the PREVENT equations, introduced by the American Heart Association in November 2023. These equations are intended to refine the tools doctors use to estimate a patient’s 10-year risk of a heart attack or stroke.

At a population level, the number of adults recommended for statins could decrease from 45.4 million to 28.3 million. At the same time, the study showed that most people who would be recommended to take statins are not currently taking them.

“This is an opportunity to refocus our efforts and invest resources in the populations of patients at the highest risk,” said lead author Dr. Timothy Anderson, M.D., M.A.S., a primary care physician at UPMC and health services researcher and assistant professor of medicine at Pitt.

Methodology of the Study

For their analysis, the team used nationally representative data from 3,785 adults, ages 40 to 75, who participated in the National Health and Nutrition Examination Survey from January 2017 to March 2020. The researchers estimated the 10-year risk of atherosclerotic cardiovascular disease (ASCVD) using the Predicting Risk of cardiovascular disease EVENTs (PREVENT) equations and compared the results to risk estimated using the previous tool, known as Pooled Cohort Equations (PCE). The PREVENT equations were developed by the American Heart Association to more accurately represent risk across the current U.S. population, as the PCE equations were based on patient data that were decades old and lacked diversity.

PREVENT also reflects more recent insights into the biology of ASCVD. Current statin use as well as metabolic and kidney diseases are incorporated into the new calculation, while race has been removed from it, reflecting a growing awareness that race is a social construct.

Using PREVENT, the team found that among the study’s entire cohort, the 10-year risk of developing ASCVD was 4%, half as high as the risk calculated by the PCE (8%). The difference was even larger for Black adults (5.1% versus 10.9%) and for adults between the ages of 70 and 75 (10.2% versus 22.8%).

An estimated 4.1 million patients who are currently taking statins would no longer be recommended to take them based on PREVENT. For these patients and their physicians, clear and careful communication is key, said Anderson. “We don’t want people to think they were treated incorrectly in the past. They were treated with the best data we had when the PCE was introduced back in 2013. The data have changed.”

At the same time, it’s important to note that everyone’s risk will inevitably change over time, as well, he added. “For a patient who we now know is at lower risk than we previously thought, if we recommend they stop taking statins, they still could be back to a higher risk five years down the road, for the simple reason that everybody’s risk goes up as we get older.”

Reference: “Atherosclerotic Cardiovascular Disease Risk Estimates Using the Predicting Risk of Cardiovascular Disease Events Equations” by Timothy S. Anderson, Linnea M. Wilson and Jeremy B. Sussman, 10 June 2024, JAMA Internal Medicine . DOI: 10.1001/jamainternmed.2024.1302

Other authors on the study were Linnea Wilson, M.P.H., of Beth Israel Deaconess Medical Center, and Jeremy B. Sussman, M.D., M.P.H., of University of Michigan, Ann Arbor.

This research was supported by the National Institute on Aging (#K76AG074878).

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5 comments on "new cholesterol guidelines could drastically reduce statin use for millions".

“…, while race has been removed from it, reflecting a growing awareness that race is a social construct.”

Statistics don’t support that naive, woke view. The social ideology behind such decisions may end up costing the lives of minorities who have a predisposition for certain diseases. Whether a particular race has predispositions for certain diseases is well established. What is less well understood is why the predispositions exist. However, be that as it may, pretending that race doesn’t correlate can be deadly because those susceptible may be less alert for symptoms. “The road to Hell is paved with good intentions.”

Everything about this study is useless. Read the article carefully and you will see all of the contradictions. When woke ideologies enter into medical research the results are corrupted .The fact is that statins are useless and dangerous. If you want to take a pill every day to lower cholesterol then take one of many natural supplements that have proven to work as well or better. Garlic and bergamot lowered my cholesterol significantly. The pharmaceutical companies have sponsored bogus studies to lie to the public about the facts. More corporate greed at the expense of our health.

Statins have been around for decades and the side effects, if any, are minimal. It is a proven fact that they are safe. I tend to trust my cardiologist more than conspiracy theories from social media. This article does not change anything for any sane person. Listen to your cardiologist.

If I’m 40 years old, I care about my 40 year risk, not my 10 year risk. Unless you are over 70, 10 year risk is extremely short sighted. My dad has always had marginally high LDL (between 100 and 130). Doctors never prescribed him statins because his 10 year risk was low. Now at age 74 he needs open heart surgery to clear plaques in the artery going to his heart. Meanwhile my mom had LDL above 250 in her 40s and was prescribed statins for decades keeping her LDL around 70-80 and her heart is perfectly fine.

If race is just a social construct, why is it hereditary?

An updated test measures how well "good cholesterol" works

It’s the cholesterol we love to love – and for good reason.

High-density lipoprotein (HDL) cholesterol, often called “good cholesterol,” removes extra cholesterol from the arteries by gobbling up early-forming plaque and transporting it to the liver, which flushes it out of the body. It’s an essential job: when too much plaque accumulates in the arteries, it can narrow blood vessels and impede blood flow, or even rupture. This can lead to severe events, including heart attacks and stroke.

Measuring how much HDL cholesterol we have in our bodies to do these tasks has long been a mainstay of the annual physical. However, within the past decade, researchers have also found that measuring whether HDL cholesterol is doing these tasks effectively can be just as valuable. The stronger the signs that a person’s “good cholesterol” is working well, they’ve discovered, the more likely they appear to have reduced risks for heart disease in the future.

There’s been one main challenge, however. Measuring HDL function is limited to research labs and isn’t conducive to large-scale testing by routine clinical laboratories. To try to solve that problem, researchers from NHLBI’s Lipoprotein Metabolism Laboratory created a new diagnostic test.

“This is going to quicken the pace of basic research,” said Edward B. Neufeld, Ph.D. , a scientist in the lab who, along with Masaki Sato, Ph.D., developed the test. “It increases the number of samples that you can study. It increases the number of experiments you can do.”

Current HDL functional assessments require researchers to harvest cells in the lab. This has to be done in small batches, often requires extra materials like radioactive cholesterol, and can take days to process. The cell-free test that Neufeld and researchers developed could be easily replicated in labs, automated to process larger samples, and provide readings in about an hour. Importantly, they have shown in clinical studies that their test can predict cardiovascular disease risk better than HDL cholesterol, which is currently used to assess such risk. They published these findings in the Journal of Clinical Investigation .

To perform the test, a person’s plasma, which contains HDL, is separated from their blood. The plasma is added to donor particles coated with a lipid mixture that resembles plaque, and a fluorescent-tagged phospholipid that can only be removed by HDL. The fluorescent signal obtained by HDL is then measured. A brighter signal reflects optimal HDL lipid removal function. A dim light indicates reduced function.

The test is still years away from potential use in a medical setting, but it holds promise for physicians looking to gather additional information that could help inform their treatment decisions. For example, a patient with intermediate risk for having a heart attack or stroke in 10 years , also found to have reduced HDL function, may emerge as a stronger candidate for treatment or for having additional assessments to measure how much atherosclerotic plaque they have. “Any additional information that we could get in terms of assigning stratification would be of great benefit,” said Neufeld. He explained that many adults have medium-level risks.

NIH has now patented the test and will work with an outside company to purchase the rights to license and manufacture the diagnostic material. “Other people may modify this or come up with better versions, which is fine with us,” said Neufeld. “We just really wanted to tackle this problem of evaluating HDL function.”

Neufeld and his colleagues believe the test could also be used for multiple purposes in research, which could lead to clinical applications, such as use in the doctor’s office. This excites them, but they caution that they still have a lot to learn. “HDL cholesterol is important, but we still don’t fully understand it,” said Alan T. Remaley, M.D., Ph.D. , a senior investigator in the Lipoprotein Metabolism Laboratory. “Biology is full of mysteries.”

Remaley explained that while HDL cholesterol research has transformed cardiovascular research, therapeutic advancements to improve HDL cholesterol haven’t followed. “Someday we may have a drug that modulates HDL and turns out to be beneficial, but right now we don’t have that,” said Remaley.

“There’s a long tradition in the field of knowing that research takes time,” Remaley explained. Like for other disciplines, incremental advancements in lipoprotein research have led to novel discoveries.

He and Neufeld envision that the updated HDL function test, which builds on previous findings, will support similar advancements. “This could open up new opportunities to gain further insights, such as with drug development, that have been difficult to achieve,” said Neufeld.

To learn about cholesterol, visit https://www.nhlbi.nih.gov/health/blood-cholesterol .

To learn about the Laboratory of Lipoprotein Metabolism, visit https://www.nhlbi.nih.gov/science/lipoprotein-metabolism .

Study challenges “good” cholesterol’s role in universally predicting heart disease risk

Lower levels of HDL cholesterol were associated with increased risks for heart attacks in white but not Black adults, and higher levels were not protective for either group.

A National Institutes of Health-supported study found that high-density lipoprotein (HDL) cholesterol, often called the “good cholesterol,” may not be as effective as scientists once believed in uniformly predicting cardiovascular disease risk among adults of different racial and ethnic backgrounds.

The research, which published in the Journal of the American College of Cardiology , found that while low levels of HDL cholesterol predicted an increased risk of heart attacks or related deaths for white adults – a long-accepted association – the same was not true for Black adults. Additionally, higher HDL cholesterol levels were not associated with reduced cardiovascular disease risk for either group.

“The goal was to understand this long-established link that labels HDL as the beneficial cholesterol, and if that’s true for all ethnicities,” said Nathalie Pamir, Ph.D., a senior author of the study and an associate professor of medicine within the Knight Cardiovascular Institute at Oregon Health & Science University, Portland. “It’s been well accepted that low HDL cholesterol levels are detrimental, regardless of race. Our research tested those assumptions.”

To do that, Pamir and her colleagues reviewed data from 23,901 United States adults who participated in the Reasons for Geographic and Racial Differences in Stroke Study (REGARDS). Previous studies that shaped perceptions about “good” cholesterol levels and heart health were conducted in the 1970s through research with a majority of white adult study participants. For the current study, researchers were able to look at how cholesterol levels from Black and white middle-aged adults without heart disease who lived throughout the country overlapped with future cardiovascular events.

Study participants enrolled in REGARDS between 2003-2007 and researchers analyzed information collected throughout a 10- to 11-year period. Black and white study participants shared similar characteristics, such as age, cholesterol levels, and underlying risk factors for heart disease, including having diabetes, high blood pressure, or smoking. During this time, 664 Black adults and 951 white adults experienced a heart attack or heart attack-related death. Adults with increased levels of LDL cholesterol and triglycerides had modestly increased risks for cardiovascular disease, which aligned with findings from previous research.

However, the study was the first to find that lower HDL cholesterol levels only predicted increased cardiovascular disease risk for white adults. It also expands on findings from other studies showing that high HDL cholesterol levels are not always associated with reduced cardiovascular events. The REGARDS analysis was the largest U.S. study to show that this was true for both Black and white adults, suggesting that higher than optimal amounts of “good” cholesterol may not provide cardiovascular benefits for either group.

“What I hope this type of research establishes is the need to revisit the risk-predicting algorithm for cardiovascular disease,” Pamir said. “It could mean that in the future we don’t get a pat on the back by our doctors for having higher HDL cholesterol levels.”

Pamir explained that as researchers study HDL cholesterol’s role in supporting heart health, they are exploring different theories. One is quality over quantity. That is, instead of having more HDL, the quality of HDL’s function – in picking up and transporting excess cholesterol from the body – may be more important for supporting cardiovascular health . They are also taking a microscopic look at properties of HDL cholesterol, including analyzing hundreds of proteins associated with transporting cholesterol and how varying associations, based on one protein or groups of proteins, may improve cardiovascular health predictions.

“HDL cholesterol has long been an enigmatic risk factor for cardiovascular disease,” explained Sean Coady, a deputy branch chief of epidemiology within the National Heart, Lung, and Blood Institute (NHLBI)’s Division of Cardiovascular Sciences. “The findings suggest that a deeper dive into the epidemiology of lipid metabolism is warranted, especially in terms of how race may modify or mediate these relationships.” The authors conclude that in addition to supporting ongoing and future research with diverse populations to explore these connections, the findings suggest that cardiovascular disease risk calculators using HDL cholesterol could lead to inaccurate predictions for Black adults.

“When it comes to risk factors for heart disease, they cannot be limited to one race or ethnicity,” said Pamir. “They need to apply to everyone.”

The REGARDS study is co-funded by the National Institute of Neurological Disorders and Stroke and the National Institute of Aging and received additional support from NHLBI. To learn more about cholesterol and heart health, visit https://www.nhlbi.nih.gov/health/blood-cholesterol . To learn about heart-healthy living, visit https://www.nhlbi.nih.gov/health/heart-healthy-living . About the National Heart, Lung, and Blood Institute (NHLBI): NHLBI is the global leader in conducting and supporting research in heart, lung, and blood diseases and sleep disorders that advances scientific knowledge, improves public health, and saves lives. For more information, visit https://www.nhlbi.nih.gov/ .

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov .

NIH…Turning Discovery Into Health ®

Zakai NA, Minnier J, Safford MM, et al. Race-dependent association of high-density lipoprotein cholesterol levels with incident coronary artery disease. J Am Coll Cardiol . 2022; doi: 10.1016/j.jacc.2022.09.027.

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Why ‘good’ cholesterol may not always be good

February 16, 2022 – For decades, it’s been known that, when it comes to heart disease risk, there’s a difference between so-called “bad cholesterol”—also known as low-density lipoprotein or LDL, which can clog up the artery walls—and “good cholesterol,” known as high-density lipoprotein or HDL, which helps clear cholesterol out of the system. Recently, drugs have been developed that increase the amount of HDL in the blood, but disappointingly failed to reduce the risk of cardiovascular disease and were never brought to market. A December paper co-authored by Harvard T.H. Chan School of Public Health researchers Jeremy Furtado , Frank Sacks , and colleagues, helps explain why the drugs didn’t work. In this Big 3 Q&A, Furtado elaborates on their findings.

Q: People call HDL “good cholesterol” because it helps remove cholesterol out of the body—but you seem to say that’s not always the case. Why is that moniker not entirely accurate?

A: In the middle of the last century, total cholesterol was an important biomarker used to assess heart disease risk. Then, in the 1970s and 1980s, researchers discovered that total cholesterol is actually made up of two very different systems, the LDL and HDL, with opposing relationships with heart disease risk. Generally speaking, cholesterol in LDL is linked to increased risk while cholesterol in HDL is associated with protection against heart disease. More recently, our group here at Harvard Chan School found that within HDL there are different subspecies that have different types of proteins on their surfaces that make them function differently from each other in the body. Given these functional differences, why should we expect that they are all protective or operate the same way? Recently, we’ve been studying 16 out of the potentially 200 or so different protein-defined HDL subspecies and found that while some are associated with a reduced risk of cardiovascular disease as you’d expect, some show no association or are even associated with increased risk. In particular, we found that HDL that contains a protein called apolipoprotein C3 (apoC3) is associated with a higher risk of cardiovascular disease, including stroke and heart attack, and type 2 diabetes . We also found that HDL that contains Complement C3 or alpha-2-Macroglobulin (α2M) is also associated with higher risk. HDLs that lack these proteins are more protective than total HDL. Conversely, HDL that contains apolipoprotein E (apoE) or apolipoprotein C1 (apoC1) is more protective against heart disease.

Q: In your study, you looked at a class of drugs called CETP inhibitors, specifically evacetrapib (Eli Lilly) and torcetrapib (Pfizer). What happened to cholesterol levels and cardiovascular disease when people took these medications?

A: CETP is a protein that moves cholesterol from HDL into LDL, so these CETP inhibitor drugs increase HDL cholesterol. While they succeeded in this, phase three clinical trials showed that there wasn’t a significant decrease in cardiovascular disease outcomes, including heart attack. So CETP inhibition wasn’t having the intended effect of reducing mortality and heart disease. The failure of these trials and trials like them, coupled with other studies that showed that naturally occurring genetic mutations that resulted in high HDL cholesterol also did not confer any protection against heart disease, implied to some that HDL was not truly an actor in the disease. Our hypothesis was that maybe the different protein-defined subspecies have different relationships with disease, some bad and some good, and perhaps these drugs didn’t work because even though they increased overall HDL cholesterol, it was the bad kinds that went up. And, in fact, we found the types of HDL that went up the most were the ones that were the worst, including those that contained apoC3.

Q: What are the health implications of these findings? Is there a way that pharma companies could retool these drugs, or other things that people can do to increase their good good cholesterol?

A: One of the most important things to come out of this study is to underscore the need to learn more about HDL subspecies to find out what functions these proteins perform. HDL isn’t just a cholesterol transporter. It also has anti-inflammatory, antioxidant, immunological, and other actions that affect disease risk. We need to find out which HDL subspecies are protective and which ones are detrimental. Once we know that, we can work to produce therapies that will target increases of the good types of HDL or reductions of the bad. And it’s not just drug therapies. Our group will soon publish new research on the effects of healthy diets associated with reduced risk of heart disease that increase HDL cholesterol, and do so by increasing the good HDL subspecies and not the bad. Stay tuned!

– Michael Blanding

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Cholesterol: Latest Research

High cholesterol raises your risk of heart disease , heart attack , and stroke . A healthy diet and lifestyle can improve your levels. Medication can help, too. Still, doctors and scientists keep studying cholesterol to see what else they can learn about it.

Here’s some progress they’ve made in the ways they think about, prevent, and treat high cholesterol.

A More Personal Approach

Doctors used to think everyone’s cholesterol level should be about the same. Now, your doctor will look at your numbers along with other risk factors you have for heart disease. Those factors include blood pressure , blood sugar , age, and weight . The higher your risk for heart issues, the lower your doctor may suggest you try to get your cholesterol levels .

Prescription for Exercise

If you have high cholesterol and mildly high blood pressure , but you have a low overall risk of heart disease, your doctor may not prescribe medication right away. New guidelines from the American Heart Association advise sitting less and moving more as the first treatment.

Physical activity can reduce LDL (low-density lipoprotein, or “bad”) cholesterol by 3 to 6 milligrams per deciliter (mg/dL) in your blood. It also lowers your blood pressure.

About 150 minutes of moderate exercise per week is ideal. But you could see a difference in your cholesterol levels with as few as 5 to 10 minutes of movement each day.

Beyond Statins

Doctors often prescribe statins to treat high cholesterol, but not everyone does well on these drugs. People who don’t respond to this type of medicine, or who have unpleasant side effects, now have some other options, such as:

PCSK9 inhibitors: PCSK9 is a protein that your liver makes. The more you have, the harder it is for your body to get rid of LDL cholesterol . A new class of drugs called PCSK9 inhibitors can block PCSK9. That way, it won’t interfere with cholesterol. You can take these medications by themselves or with statins . You get them through a shot, usually about every 2 weeks.

If you have a genetic condition called familial hypercholesterolemia , PCSK9 inhibitors may work better for you than statins do.

SiRNA therapy: SiRNA (small interfering RNA) therapy can treat some health conditions by changing how some of your genes work. A new medication called inclisiran ( Leqvio ) uses this technology to treat adults with heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular disease (ASCVD) who need additional LDL lowering. It lowers your LDL levels by disrupting the gene that makes PCSK9. Inclisiran comes in the form of shots, taken several months apart. You can use this medication along with other cholesterol-lowering treatments or alone.
Bempedoic acid: Like statins, this new medication makes it harder for cholesterol to form in your body. Bempedoic acid, which is a pill you swallow, may lower your LDL levels by up to 15%. For now, you can get a prescription only if you have a family history of high cholesterol or you have atherosclerotic cardiovascular disease (ACD).

Nanotech That ‘Eats’ Plaque

Cholesterol can cause fatty deposits called plaque to form inside your arteries . Over time, it can start to block your blood flow. This condition, called atherosclerosis , raises your risk of heart problems and stroke . Scientists have recently created a nanoparticle -- a tiny object that the naked eye cannot see -- to eat away at this waxy buildup. It’s still in testing mode, but in the future, a drug that contains this nanoparticle could be part of atherosclerosis treatment.

Gut Health Could Help

Researchers have thought for some time that gut health plays a role in cholesterol levels , but it hasn’t been clear exactly how. But they now know that probiotics (“good” live bacteria) and prebiotics (which feed useful germs in your gut) can lower LDL cholesterol and triglycerides , another type of blood fat. These gut bacteria may also increase high-density lipoprotein (HDL, or “good”) cholesterol.

Talk to your doctor if you’re interested in trying probiotics or prebiotics. The amount you need in order to get results is still under review, and too much could lead to an upset stomach .

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Published: 01 August 2024

Cholesterol imbalance and neurotransmission defects in neurodegeneration

Kyung Chul Shin ORCID: orcid.org/0000-0003-3684-4005 1 ,
Houda Yasmine Ali Moussa 1 &
Yongsoo Park 1 , 2

Experimental & Molecular Medicine ( 2024 ) Cite this article

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Neurodegeneration
Synaptic vesicle exocytosis

The brain contains the highest concentration of cholesterol in the human body, which emphasizes the importance of cholesterol in brain physiology. Cholesterol is involved in neurogenesis and synaptogenesis, and age-related reductions in cholesterol levels can lead to synaptic loss and impaired synaptic plasticity, which potentially contribute to neurodegeneration. The maintenance of cholesterol homeostasis in the neuronal plasma membrane is essential for normal brain function, and imbalances in cholesterol distribution are associated with various neurodegenerative disorders, including Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. This review aims to explore the molecular and pathological mechanisms by which cholesterol imbalance can lead to neurotransmission defects and neurodegeneration, focusing on four key mechanisms: (1) synaptic dysfunction, (2) alterations in membrane structure and protein clustering, (3) oligomers of amyloid beta (Aβ) protein, and (4) α-synuclein aggregation.

The translational potential of cholesterol-based therapies for neurological disease

Cholesteryl ester levels are elevated in the caudate and putamen of Huntington’s disease patients

Sterol auto-oxidation adversely affects human motor neuron viability and is a neuropathological feature of amyotrophic lateral sclerosis

Introduction.

Cholesterol is a lipid that is critical for the structure and function of cell membranes in the brain, where it participates in neuronal signaling and synaptic transmission. The brain contains the highest concentration of cholesterol in the human body, accounting for 20–25% of the total cholesterol 1 , 2 . The blood–brain barrier (BBB) is impermeable to peripheral cholesterol 3 ; therefore, most cholesterol in the brain is generated by de novo synthesis, mainly in the glia and to a lesser extent in neurons 3 . The high cholesterol concentration suggests an important role for cholesterol in brain physiology.

Cholesterol is involved in neurogenesis and synaptogenesis 4 , 5 . Age-related reductions in cholesterol levels in the plasma membrane lead to synaptic loss 6 , 7 and impaired synaptic plasticity 8 , suggesting that cholesterol imbalance in the neuronal plasma membrane affects neuronal activity and contributes to neuronal degeneration 9 , 10 . The maintenance of cholesterol homeostasis is essential for normal brain functions 11 , 12 , 13 . An imbalance in cholesterol distribution can cause the pathological changes observed in various neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD), suggesting that neurodegenerative diseases are associated with dysregulated cholesterol distribution 11 , 12 , 14 .

The aim of this review is to examine the molecular and pathological mechanisms by which cholesterol imbalance causes neurotransmission defects. This review focuses on four molecular mechanisms to explain how cholesterol imbalance in neurons results in neurodegeneration: (1) synaptic dysfunction, (2) membrane structure and protein clustering, (3) amyloid beta (Aβ) aggregation, and (4) α-synuclein (α-syn) aggregation.

The molecular mechanisms of neurodegeneration induced by cholesterol imbalance

Cholesterol has a complex and multifaceted role in neurodegeneration. Given that cholesterol is an essential component of cell membranes and is involved in various physiological processes in the brain, an imbalance and dysregulation of cholesterol homeostasis can contribute to the pathogenesis of neurodegenerative diseases 11 , 12 , 14 . Table 1 summarizes the links between cholesterol and different neurodegenerative diseases. Several mechanisms have been proposed to explain how cholesterol imbalance may contribute to neurodegeneration:

Synaptic dysfunction: cholesterol is critical for the formation and function of synapses, the connections between neurons that facilitate communication in the brain. Altered cholesterol levels can affect synaptic transmission and plasticity, impairing neuronal signaling and contributing to the cognitive deficits observed in neurodegenerative diseases. The plasma membrane is enriched with cholesterol, ~80% of which is cellular cholesterol 15 . Therefore, reduced cholesterol levels in the plasma membrane, i.e., cholesterol imbalance, impairs synaptic transmission and plasticity and thus induces neurodegeneration 9 , 10 , 16 .

Depletion and imbalance of cholesterol in the plasma membrane cause deficits in neurotransmission; e.g., cholesterol depletion reduces Ca 2+ -dependent exocytosis of large dense-core vesicles (LDCVs) 17 , cortical secretory vesicles 18 , and synaptic vesicles in hippocampal neurons 9 , 19 , cortical synaptosomes 20 , ribbon synapses 21 , and motor nerve terminals 22 . However, unveiling the molecular pathology of cholesterol imbalance in neurodegeneration is challenging because cholesterol is involved in various cellular signaling processes and neuronal functions. The reconstitution system of vesicle fusion with purified native vesicles, including LDCVs and synaptic vesicles, can be a good model for elucidating the molecular mechanisms by which cholesterol deficiency affects vesicle fusion 23 (Fig. 1 ).

Cholesterol is essential for Ca 2+ -dependent vesicle fusion. Synaptotagmin-1, a Ca 2+ sensor that triggers fusion, induces local deformation of the plasma membrane. The plasma membrane is normally flexible and can return to its original shape due to membrane elasticity. However, cholesterol makes the membrane less fluid and more rigid, which helps to strengthen the membrane curvature and deformation, thus lowering the energy barrier for fusion. This image was created with BioRender.com.

This reconstitution of vesicle fusion shows that cholesterol has little effect on Ca 2+ -independent basal fusion of synaptic vesicles but is required for Ca 2+ -dependent fusion of LDCVs and synaptic vesicles 23 . It is surprising that cholesterol reduction and imbalance specifically disrupt Ca 2+ -dependent vesicle fusion. Cholesterol has no effect on the membrane binding or insertion of synaptotagmin-1, a Ca 2+ sensor for vesicle fusion 23 . Once synaptotagmin-1 is inserted into the membrane, cholesterol stabilizes and strengthens the local membrane bending and deformation induced by synaptotagmin-1 23 . The membrane is highly flexible, so it can reform into its original shape due to membrane elasticity 24 . Because cholesterol reduces membrane fluidity and increases membrane rigidity 25 , cholesterol can strengthen local membrane deformation and bending, thus lowering the energy barrier for Ca 2+ -dependent fusion 23 (Fig. 1 ).

Membrane bending and curvature play crucial roles in the process of vesicle fusion by lowering the energy barrier 26 . The energy stored in the curvature of the membrane can be released to facilitate the merging of two separate lipid bilayers 26 , 27 , 28 . For instance, smaller vesicles, which have a greater curvature, have greater bending energy per unit surface area, leading to a more efficient fusion process 26 . The insertion of proteins such as the C2AB domain of synaptotagmin-1 into the plasma membrane contributes to this curvature 29 , 30 , creating a high-energy state that can drive vesicle fusion.

Cholesterol enhances membrane curvature and thus lowers the energy barrier for fusion 18 . It also strengthens local bending and deformation, particularly in the presence of Ca 2+ and synaptotagmin-1, thereby driving Ca 2+ -dependent vesicle fusion 23 . Mechanical forces of membrane bending are critical for the dynamic process of vesicle fusion 31 , and cholesterol is an essential lipid for synaptic transmission because it strengthens membrane bending 23 .

Synaptic transmission involves the release of neurotransmitters from synaptic vesicles into synapses, where neurotransmitters bind to receptors on postsynaptic neurons, thereby transmitting signals across the neural network 32 . When synaptic transmission is impaired due to disruptions in Ca 2+ -dependent vesicle fusion, neural network formation becomes impaired 33 . Disruption of Ca 2+ -dependent vesicle fusion and synaptic transmission via a cholesterol imbalance in the plasma membrane leads to reduced neural network activity and synaptic dysfunction and ultimately contributes to neurodegeneration. The loss of the neural network caused by the dysregulation of cholesterol homeostasis can result in declines in cognitive and motor functions associated with neurodegenerative diseases.

Membrane structure and protein clustering: cholesterol regulates membrane structure, fluidity, and curvature 25 . The plasma membrane is enriched in cholesterol 15 , which stabilizes membrane curvature and promotes vesicle fusion 17 , 25 , 34 , 35 . The membrane curvature and deformation stabilized by cholesterol bring the two membranes close together and enable fusion. Cholesterol also contributes to vesicle fusion by stabilizing fusion pores 25 , 36 , 37 , 38 . Therefore, cholesterol deficiency in neurons causes defects in membrane structure, resulting in neurodegeneration.

Cholesterol also mediates the protein clustering involved in vesicle fusion. Exocytosis of neurotransmitter release is mediated by soluble N -ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins 39 , 40 . Neuronal SNARE proteins consist of Q-SNARE in the plasma membrane (syntaxin-1 and SNAP-25) and R-SNARE in the vesicle membrane (synaptobrevin-2 or vesicle-associated membrane protein-2 (VAMP-2)) 39 . Specialized microdomains within the plasma membrane, e.g., lipid rafts, detergent-resistant membranes, or liquid-ordered membrane microdomains, are enriched in cholesterol and concentrate signaling molecules 41 , 42 , 43 . Cholesterol plays an important role in the function and organization of SNARE proteins; syntaxin-1A, a neuronal SNARE protein, is concentrated in cholesterol-enriched domains in the plasma membrane 44 , 45 . The cholesterol-enriched membrane microdomains provide a specialized environment where syntaxin-1A interacts with its binding partners. In the context of synaptic transmission, the clustering of syntaxin-1A in cholesterol-enriched microdomains may enhance its interactions with other SNARE proteins, such as SNAP-25 and VAMP-2, to form the core SNARE complex necessary for vesicle fusion. This organization may influence the overall stability and efficiency of neurotransmitter release at the synapse, suggesting that cholesterol imbalance leads to defects in the clustering of the vesicle fusion machinery.

Oligomers of amyloid beta (Aβ) protein: cholesterol imbalance influences the aggregation and misfolding of proteins involved in neurodegenerative diseases, such as amyloid precursor protein (APP) 46 . The accumulation of Aβ plaques in the brain is a hallmark pathology of AD 47 , 48 . Aβ is derived from APP through enzymatic cleavage by the β-secretase Bace1 49 , and cholesterol modulates the processing of APP and the generation of Aβ 50 , 51 . High cholesterol levels can promote and accelerate the cleavage of APP by Bace1, resulting in increased Aβ production and aggregation, which contributes to the formation of toxic plaques 50 , 51 , 52 .

Aβ40/Aβ42 peptides are the primary constituents of Aβ oligomers and plaques, which can be stabilized by biomolecules, including carbohydrates, nucleic acids, and lipids, e.g., cholesterol 53 . Extracellular cholesterol strengthens Aβ fibrils and oligomers against degradation by directly binding to Aβ 53 , 54 . Cholesterol has been implicated in the aggregation of Aβ peptides, particularly in the formation of Aβ oligomers 55 , 56 , 57 . Free cholesterol interacts with specific residues in Aβ peptides, particularly Phe19 55 . Cholesterol binds to the aromatic side chains of the Aβ peptide, thus increasing β-sheet formation in Aβ peptide oligomers 55 . A stable interaction between cholesterol and Phe19 leads to the formation of Aβ oligomers 55 , suggesting that the interaction of cholesterol with Aβ contributes to the formation of toxic Aβ oligomers, which play a critical role in AD pathology 57 .

Cholesterol dramatically enhances and accelerates the onset of Aβ42 aggregation through a heterogeneous nucleation pathway 58 . Cholesterol imbalance and elevated extracellular levels of cholesterol can promote the production and accumulation of Aβ peptides, which induce the formation of Aβ oligomers in the brain, thus contributing to neuronal damage and cognitive decline 57 (Fig. 2 ). Aβ monomers misfold and form β-sheet-rich oligomers that eventually impair synaptic plasticity and neuronal survival 59 . The direct interaction of cholesterol with Aβ can stimulate and activate toxic Aβ oligomerization, which is a critical factor in AD pathogenesis.

Cholesterol enhances and accelerates APP cleavage by Bace1, leading to increased Aβ oligomer and plaque formation. Cholesterol binds to Aβ and increases the resistance of Aβ fibrils and oligomers to degradation. Cholesterol imbalance and high extracellular cholesterol levels can stimulate the production and accumulation of Aβ peptides, which cause Aβ oligomer formation and aggregation in the brain, resulting in neuronal damage. This image was created with BioRender.com.

The membrane curvature induced by cholesterol might contribute to Aβ aggregation 60 . High membrane curvature promotes Aβ nucleation, accelerating amyloid fibril formation 61 . Aβ aggregates can readily form on membranes with high curvature 62 . High membrane curvature, such as that associated with lipid rafts and membrane budding processes, might provide favorable conditions for the nucleation of Aβ peptides 61 , 62 , 63 . Given that cholesterol stabilizes high membrane curvature, cholesterol-mediated curvature of membranes may lead to altered lipid packing that engages Aβ hydrophobic groups and promotes Aβ fibrillar structures 64 . Lipid packing defects that occur in curved membranes may induce conformational changes in Aβ peptides, thus promoting Aβ fibrils and aggregation 64 . This aggregation is a hallmark of AD, and understanding the underlying mechanisms of membrane curvature is crucial for developing potential therapeutic strategies. The interplay between membrane curvature and Aβ aggregation is complex, and ongoing research continues to unveil the molecular details involved.

Tau aggregation: while Aβ oligomers and aggregation are primarily associated with AD, another hallmark of AD is the aggregation of hyperphosphorylated tau proteins into neurofibrillary tangles (NFTs) 65 . Tau is a cytoskeletal protein that stabilizes microtubules in neurons, but it is hyperphosphorylated in AD 66 . The interaction between tau proteins and cell membranes, particularly in cholesterol-rich regions, is a critical factor in the tau aggregation process 67 , 68 . The membrane binding of tau can induce conformational changes and aggregation with β-sheet-rich structures 69 . NFTs in AD brains contain cholesterol 54 , 70 , which could modulate tau-membrane interactions and affect tau aggregation 68 , 71 .

As cholesterol can influence membrane curvature, high membrane curvature caused by cholesterol can induce changes in the conformation of tau proteins and promote tau aggregation 72 . Membranes with high curvature that contain cholesterol induce tau fibril formation, whereas cholesterol depletion abolishes tau fibril formation 72 . Cholesterol-free membranes fail to induce the formation of tau fibrils, suggesting that cholesterol-mediated tau aggregation is essential for the pathology of tauopathies 72 . Membrane morphologies result in different hydrophobic interactions that lead to the β-sheet structures of tau proteins 72 . The association of tau with highly curved membranes is initiated by electrostatic attraction between the Lys sidechains of tau and the lipid headgroups; cholesterol might further strengthen this electrostatic attraction for tau fibril formation 72 . However, how cholesterol facilitates tau nucleation remains a topic of further study, and understanding the underlying molecular mechanisms is crucial for developing therapeutic strategies involving the disruption of tau aggregation.

α-Synuclein (α-syn) aggregation: a characteristic feature of PD is the accumulation of misfolded α-syn proteins in Lewy bodies (LBs) 73 . The interaction between α-syn and lipids is important for fibril formation, and the aggregation of α-syn is induced by binding to membrane lipids 74 . Lipids dramatically enhance the primary nucleation of α-syn to form aggregates associated with neurodegeneration 74 .

Together with α-syn, cholesterol, which is a component of LBs 75 , accelerates α-syn aggregation and LB formation 76 . Cholesterol interacts with α-syn, and high cholesterol levels can promote α-syn aggregation 76 , 77 , leading to the formation of toxic LBs, which contributes to neurodegeneration in PD.

α-Syn binds to membranes through electrostatic interactions and hydrogen bonding, but cholesterol reduces the coulomb interactions and hydrophobic interactions between α-syn and membranes 78 . Cholesterol decreases lipid packing defects and lipid fluidity, thereby dysregulating the membrane binding of α-syn 78 ; membrane-bound α-syn can have a β-sheet structure that induces the formation of toxic α-syn oligomers and fibrils. Together, the imbalance and dysregulated distribution of cholesterol in neurons cause neurodegeneration by accelerating α-syn aggregation and LB formation.

Possible therapeutic approaches for cholesterol imbalance

The apolipoprotein E (ApoE) gene is involved in the metabolism and transport of cholesterol 79 , 80 . There are three main variants or alleles of the APOE gene, namely, ApoE2, ApoE3, and ApoE4 81 . The ApoE4 protein is the most important risk factor for late-onset AD 82 , i.e., the most common form of the disease that occurs after age 65. The molecular mechanisms by which ApoE4 contributes to AD are complex and not fully understood, but ApoE4 likely promotes Aβ aggregation by transporting cholesterol 79 , 83 . ApoE4 can induce cholesterol imbalance by transporting cholesterol from the plasma membrane in neurons to protein aggregates (Fig. 2 ). Given that cholesterol imbalance causes neurodegeneration, ApoE4 may be a possible target for mitigating Aβ aggregation and treating cholesterol imbalance.

Overall, the maintenance of cholesterol homeostasis is important for preventing or slowing the pathogenesis of neurodegenerative diseases. Strategies aimed at regulating cholesterol levels or targeting cholesterol-mediated pathways involved in protein aggregation might be potential therapeutic approaches to treating neurodegenerative diseases, although neurodegenerative diseases are complex and cholesterol imbalance is one of many contributing factors 11 , 84 .

Cholesterol is an essential component of the body that helps maintain the integrity of cell membranes. The role of cholesterol dysregulation in neurodegeneration is an active area of research, and the precise mechanisms involved may vary depending on the specific condition. The balance between the beneficial and detrimental effects of cholesterol remains complex. An imbalance in cholesterol regulation is a common feature of neurodegenerative conditions such as AD and PD. Therapeutic approaches for modulating cholesterol metabolism or targeting specific cholesterol-related pathways could be potential strategies for mitigating neurodegeneration. While cholesterol-lowering drugs, e.g., statins, have shown some potential in reducing the risk of certain neurodegenerative diseases, further research is required to fully understand the role of cholesterol and develop targeted therapeutic interventions.

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Acknowledgements

This work was supported by grants from the Qatar Biomedical Research Institute (Project Number SF 2019 004 and IGP5-2022-001 to Y.P.) and the HBKU Thematic Research Grant (Project Number VPR-TG02-06 to Y.P.).

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Shin, K.C., Ali Moussa, H.Y. & Park, Y. Cholesterol imbalance and neurotransmission defects in neurodegeneration. Exp Mol Med (2024). https://doi.org/10.1038/s12276-024-01273-4

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June 1, 2023

Too Much ‘Good’ Cholesterol Can Harm the Heart

HDL cholesterol raises disease risk at levels above 80 milligrams per deciliter

By Lydia Denworth

An illustration depicting doctors in white coats surrounding a human heart with a meter reading over it.

Anyone who has annual check-ups, as I do, knows that an optimal cholesterol level consists of not one number but two. Low-density lipoprotein cholesterol (LDL) should be less than 130 milligrams per deciliter (mg/dL), ideally. High-density lipoprotein cholesterol (HDL) should be more than 40 mg/dL. LDL plays the villain in this story, the “bad” cholesterol to HDL's heroic role as the “good” cholesterol .

This idea came out of the Framingham Heart Study, the pioneering research project, begun in 1948, that identified many risks for cardiovascular disease. High levels of LDL increase a person's risk of heart attacks and stroke because it builds up in artery walls and can cause atherosclerosis. HDL at higher levels, in contrast, can lower overall cholesterol levels by binding with LDL and moving it to the liver, where it is excreted as waste. A person's ratio of one type to the other type matters.

But recent research shows that the story of HDL is not so simple—more Goldilocks than Jekyll and Hyde. Those studies reveal that too little HDL is insufficient to lower LDL, but too much HDL actually heightens the risk of death. The “just right” amount of HDL lies between 40 and 80 mg/dL.

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In a study of more than 400,000 people from the general population in the U.K., men with HDL levels below 40 or above 80 and women with levels above 100 were at greater risk of both mortality from all causes and cardiovascular death in particular. There were similar findings in people who already had certain risky conditions. Two smaller groups of patients with coronary artery disease and HDL levels above 80 had an alarming 96 percent higher risk of dying overall than those with lower HDL levels. And a study of more than 11,000 people with hypertension in Italy found significantly higher risk of cardiovascular events in those with HDL levels below 40 and above 80.

High levels of HDL have also been shown to affect bone density. Research on more than 16,000 Australians over the age of 70 found that those with the highest HDL levels were at a 33 percent higher risk of suffering fractures than those with lower levels.

Additional troubling evidence comes from clinical trials for drugs such as niacin that attempt to raise HDL levels on the theory that higher is better. “Those drugs were never shown to be of benefit when they were employed” along with statins, drugs that lower LDL levels, says Arshed Quyyumi, director of the Emory Clinical Cardiovascular Research Institute and a co-author of two of the recent studies.

No one knows why high levels of HDL are so harmful. “That's the million-dollar question,” says cardiologist Gaetano Santulli of Albert Einstein College of Medicine, who is studying HDL. One possibility is that at higher levels, the structure of HDL molecules changes in a way that prevents them from binding tightly with circulating cholesterol to help clear the excess from the blood, Santulli says. Or it could be that at very high levels, overall amounts of cholesterol tip into the danger zone.

Fortunately, very high levels of HDL are found in less than 7 percent of the general population—one reason the risk that they carry was missed. They are more common in women but prove riskier in men, so ongoing studies are investigating the possibility that estrogen is protective.

Unfortunately, HDL levels are mostly out of individual control. They rise with exercise and with modest alcohol consumption—although heavy drinking increases total cholesterol and cardiac risk —but there appears to be little a person can do to lower them if they become excessive. We should, therefore, focus on keeping “bad” LDL levels low. Statins have been well established as reducing cardiovascular risk. In addition, a healthy lifestyle is key, says Monira Hussain, a chronic disease epidemiologist at Monash University in Melbourne, Australia, and a co-author of the bone fracture study. High-fiber, low-fat diets and increased physical activity help to lower LDL levels. Smoking is doubly harmful: it raises LDL and lowers HDL.

Cardiologists, for their part, need to change how they assess risk in their patients. “Oftentimes we go around telling people, ‘Your HDL is sky-high. You're so protected,'” Quyyumi says. We now know that isn't true and that—like Goldilocks—we should all aim for the middle ground.

This is an opinion and analysis article, and the views expressed by the author or authors are not necessarily those of Scientific American.

heart health

7 Myths About Cholesterol, Debunked

Y ou may not recall every lab value from your last physical, but you probably remember one: Your cholesterol level.

If it’s higher than ideal, you’re not alone. According to the U.S. Centers for Disease Control and Prevention, between 2015 and 2018, almost 12% of U.S. adults ages 20 and up had high total cholesterol, defined as above 240 mg/dL. The type that physicians mostly worry about is LDL (or “bad”) cholesterol, which is one component of that total.

Why do doctors care so much about cholesterol ? First, “it predicts risk,” says Dr. Jeffrey Berger, a cardiologist and director of the Center for the Prevention of Cardiovascular Disease at NYU Langone in New York City. “It’s been shown in probably hundreds of studies that higher levels of LDL cholesterol is associated with a higher risk of having a heart attack, stroke, or early death.” And, crucially, it’s possible to modify this risk factor. “Numerous studies have shown that when you lower cholesterol, you decrease the risk of a cardiovascular event,” Berger says.

Doctors’ understanding of cholesterol, including how to best manage it, has evolved over the years. Read on for the latest information from experts.

The myth: Cholesterol is always harmful.

The facts: Cholesterol, which is often described as a fat-like, waxy substance, is essential to the human body, including playing a key role during fetal development. It’s part of cell membranes and prompts production of crucial hormones. But too much can cause problems, namely contributing to clogged arteries and raising the risk of heart problems. When physicians and researchers talk about cholesterol’s harms, they’re usually referring specifically to low-density lipoprotein. LDL transports cholesterol around the body, depositing it in blood vessels, explains Nathalie Pamir, an associate professor in preventive cardiology at the Oregon Health & Science University in Portland. Its smaller cousin, high-density lipoprotein (HDL), has long been thought of as the “good” cholesterol because it typically ferries cholesterol away from other parts of the body to the liver.

More from TIME

Because LDL and HDL are different, doctors no longer focus so closely on the total amount of cholesterol. Instead, they generally ask people to aim for lower levels of LDL (optimally, below 100 mg/dL) and higher levels of HDL (at least 60 mg/dL, and not below 40 md/dL).

The myth: ‘Good’ cholesterol is always protective.

The facts: The story has gotten more complicated. LDL is still considered to be a bad actor: “Based on current research, there is no level where having it really low is dangerous,” says Dr. Leslie Cho, section head of preventive cardiology and rehabilitation at the Cleveland Clinic. In fact, people with heart disease should aim for less than 70 mg/dL, and people with diabetes and those at very high risk of coronary artery disease are advised to aim for less than 55 mg/dL, she says.

But the HDL story is more complex. Trials of experimental drugs for increasing HDL have not actually reduced heart events, and research has cast doubt on the idea that the higher the HDL levels, the better. Pamir and colleagues published a study in November in the Journal of the American College of Cardiology that followed nearly 24,000 adults without heart disease over about a decade to measure biomarkers and track heart attacks and heart attack-related deaths. While LDL, as well as another form of lipid, triglycerides, “modestly predicted” risk in white and Black adults, low HDL levels were associated with increased risk only in white adults. And high levels of HDL weren’t protective for either white or Black adults.

One potential explanation, Pamir says, is that the quality of the HDL’s functioning may matter more than the sheer quantity. There’s some evidence that high levels may indicate harmful inflammation, Wright adds. And excessive alcohol use or metabolic disorders may lead to higher HDL levels but not to better health. For now, there’s no test for the quality of HDL. Research into the intricacies of HDL by Pamir and others continues. Until there are more definitive answers, it’s important for people with high levels of HDL not to assume it will protect them from heart problems, to take the lifestyle steps that are known to improve heart health, and to talk with their physicians about medication if other factors suggest a higher heart disease risk, cardiologists say.

Read More: What to Know About High Cholesterol in Kids

The myth: You don’t need to get your cholesterol checked until you reach the average age for heart attacks.

The facts: Recommendations vary on when to start, but the AHA recommends that all low-risk adults ages 20 and older have their levels checked every four to six years. Screening will likely be more frequent if you have a family history or a personal history of heart disease. And the American Academy of Pediatrics recommends all children be screened for high cholesterol between the ages of 9 and 11—earlier if they have risk factors like a family history of early heart disease.

Cholesterol is measured using a blood draw. According to guidelines published in 2016, it’s usually not necessary to fast before your test. (Ask your doctor ahead of time to make sure.)

The myth: You have no control over your cholesterol levels.

The facts: To be sure, some influences on cholesterol are beyond your control. Infants are born with very low LDL cholesterol and levels “keep going up and up” as we age, Cho says. When women hit menopause and estrogen—which helps regulate lipid levels—wanes, their levels of LDL and triglycerides increase. “It’s an aging process. It’s not a moral failure,” Cho says. There are also racial differences. About 9.2% of Black male adults and 10.5% of Black female adults had high cholesterol between 2015-18, compared to 10.1% for white men and 13.1% for white women, according to a report from the American Heart Association.

But there are definitely some things you can do to keep your cholesterol in check, such as exercising. Regular high-intensity workouts, including running or biking at a good pace, can lower cholesterol by at least 10%, Wright says. Exercise also helps people sleep better and reduce stress, which can improve your heart and overall health. “No medication can replicate the physiological benefits of exercise,” Wright says.

And while weight loss can be difficult, you don’t have to lose much to see a positive effect. A 2016 review of weight-loss studies found that even losing 5-10% of your weight—so 10 to 20 pounds for a 200-pound person—resulted in “significant” reductions in total cholesterol, LDL cholesterol, and triglycerides. (Losing more weight was associated with larger improvements.)

The myth: If you have low cholesterol, you won’t have a heart attack.

The facts: This is “not at all” true, Cho says. Cholesterol is an important risk factor, but it’s not the only one, nor is it a perfect indication. Other heart risk factors include age (older people are more at risk), male gender, diabetes, tobacco use, and obesity, according to the American Heart Association (AHA). And an estimated 20% of total risk for what causes someone to have a heart attack isn’t known,” says Dr. R. Scott Wright, professor of cardiology at Mayo Clinic in Rochester, Minn. So don’t get too laser-focused on that number. “If you could choose between a life of high cholesterol yet a low risk of heart attack and stroke, or the opposite—low circulating LDL cholesterol yet a high risk of heart disease—you’d pick the first one,” Berger says. “You care about whether you’re going to have a heart attack or stroke.”

The myth: To keep your cholesterol low, you should avoid eggs.

The facts: If you’re a certain age, you may remember when “cholesterol-free” was plastered all over food packages. The U.S. Department of Agriculture used to recommend consuming less than 300 mg per dietary cholesterol per day. It stopped recommending a specific level in the 2015-20 nutrition guidelines, in part because Americans were, on average, not significantly exceeding that. In addition, the American Heart Association noted in a 2019 scientific advisory on dietary cholesterol that “evidence from observational studies conducted in several countries generally does not indicate a significant association with cardiovascular disease risk.”

Moreover, eating more cholesterol in your diet doesn’t necessarily translate to higher blood cholesterol for most people. The body also makes its own and can adjust to compensate if you eat more or less. That said, some people are highly sensitive to changes in their dietary cholesterol, and blood levels will fall dramatically if they lower their consumption, Cho says.

What does seem to increase LDL cholesterol are the types of fat that are “solid at room temperature,” Cho says. Those include saturated fats from animal products including meat, butter, and dairy. By contrast, unsaturated fats—which are liquid at room temperature—are beneficial. And eating too many simple carbs can lead to weight gain, Wright says. Rather than singling out specific foods, cardiologists now recommend a healthy eating pattern that incorporates plenty of fruits and vegetables, more healthful proteins such as fish, and monounsaturated fats. The Mediterranean diet fits the bill, cardiologists say, and has been associated with protection against other diseases, including diabetes and cancer.

Read More: How to Lower Your Cholesterol Naturally

The myth: You can always control your cholesterol level without help from medications.

The facts: Not all risk factors can be addressed. You can’t do anything about your age; nor can you change your genetic makeup. An inherited disorder called familial hypercholesterolemia causes about 1 in 200 people to be born with high LDL cholesterol levels, which will continue to rise throughout childhood and adulthood. It usually leads to heart disease, according to the AHA, though it can be treated with lifestyle measures and medications. While it’s a rare condition, other risk factors—such as weight and body type—also have genetic influences.

Even with weight loss and exercise, your physician may advise medications to keep your cholesterol in check. The most common are called statins , which decrease LDL levels. They are routinely prescribed to people who have already had a cardiac event to prevent another one, and also for preventing a heart event in the first place in those who are at increased risk. An updated evidence report from the U.S. Preventive Services Task Force, published in August 2022, found that using statins in at-risk populations was associated with a lower risk of cardiac events and death. The benefits occurred “across diverse demographics and clinical populations,” the review said.

Statins are “by far the most well-known [medication], and have the most amount of data,” Berger says. There are also newer drugs, he says, such as ezetimibe and PCSK9 inhibitors. The decision to prescribe medication is often based on risk calculators that gauge the 10-year risk of heart disease; most recent guidelines put the threshold at a 7.5% risk over the next decade, or 5% if the person has other high-risk features, he says. You should have a detailed conversation with your physician about the benefits and risks of medications.

Still, Berger emphasizes, exercise and diet are the first things to try, not just because they can improve your cholesterol, but because they improve overall health. A study published in the New England Journal of Medicine found that among people with a high genetic risk of heart disease, a healthy lifestyle (including diet and exercise) was associated with a 46% lower relative risk of coronary events than an unfavorable one.

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How levels of 'good' cholesterol may increase dementia risk

So-called “good” HDL cholesterol may not be as healthy as experts once thought, a new study suggests.

The new study , published Wednesday in Neurology, found that having either high or low levels of high-density lipoprotein, or HDL, cholesterol, may increase the risk of dementia in older adults. It’s more evidence showing that keeping HDL cholesterol within a certain range is important for cardiovascular and brain health.

“The relationship between HDL cholesterol and dementia is more complex than we previously thought," said the study’s lead author, Erin Ferguson, a doctoral student studying epidemiology at the University of California San Francisco. "While the magnitude of this relationship is relatively small, it’s important,”

The results show a correlation between HDL cholesterol and dementia, but do not prove that low or high levels of the lipid directly caused dementia.

The study, which was supported by the National Institute on Aging and the National Institutes of Health, included more than 184,000 adults with an average age of 70. None had dementia when the study began. Researchers used a combination of surveys and electronic records from the Kaiser Permanente Northern California health plan to track cholesterol levels, health behaviors and whether someone developed dementia over about 13 years. During that time, just more than 25,000 people developed dementia.

The Centers for Disease Control and Prevention recommends people keep their total cholesterol at about 150 mg/dL, or milligrams per deciliter of blood, with LDL at or below 100 mg/dL. Low-density lipoprotein, or LDL, cholesterol, has long been recognized for its often deadly impact on the cardiovascular system.

The study’s participants were divided into three groups based on their HDL cholesterol levels, with adjustments for other dementia risk factors, including high blood pressure, heart disease, diabetes and how often a person drinks.

What is a healthy level of HDL?

The average HDL cholesterol level in the study was 53.7 mg/dL, within the recommended range of 40 mg/dL in men and 50 mg/dL in women.

People whose cholesterol levels strayed too far from these numbers were more likely to develop dementia over the course of the study.

People whose levels were at least 65 mg/dL — the highest of the three groups — were 15% more likely to develop dementia. Those with the lowest levels — 11 to 41 mg/dL — had a 7% increased risk compared to the middle group.

The researchers didn’t find any association between LDL cholesterol and dementia risk.

Dr. Howard Weintraub, clinical director of the Center for the Prevention of Cardiovascular Disease at NYU Langone Heart in New York, said he was surprised by the findings.

“When people have HDL that’s 90 or 100 mg/dL, that can be associated with increased cardiovascular risk, not necessarily dementia. These lower numbers, 53-63 mg/dL, have also not been associated with greater risk,” said Weintraub, who was not involved with the research.

Experts have long understood that not all HDL cholesterol is equal. How the body uses it and where it’s stored –– in the brain or elsewhere in the body –– make a difference.

How to improve HDL

Healthy habits, including exercise, allow HDL cholesterol to become HDL particles. This allows HDL to perform some of the important tasks it’s touted for, including removing LDL cholesterol from the arteries and transporting it to the liver, where the body gets rid of it, said Dr. Hussein Yassine, an endocrinologist at the Keck Medicine of USC who specializes in how changes in lipid metabolism impact a person’s risk of developing Alzheimer’s disease.

“The function is really in the particles, not the cholesterol itself,” he said. “Simply increasing HDL levels does not increase its function.”

High HDL cholesterol levels can stiffen veins and arteries. This impact on the cardiovascular system is a key way high levels of HDL cholesterol may increase risk of cognitive impairment –– stroke is one of the leading risk factors for dementia. HDL cholesterol in the brain acts in a completely different way.

“It operates on different rules and has different pathways than systemic cholesterol,” Yassine said. Systemic cholesterol is cholesterol stored elsewhere in the body, outside the brain.

Too much HDL cholesterol in the brain can cause inflammation that prompts the brain to produce amyloids, abnormal deposits that damage organs and tissues, he added.

Another recent study established a connection between genes linked to high HDL cholesterol levels and those that predispose someone to dementia.

Together, the studies point to the fact that HDL cholesterol is both complex and an area of research that needs to be better understood.

Weintraub said there isn’t yet enough evidence to say that HDL cholesterol plays a significant role in dementia risk

“This paper might suggest that HDL could be a modifiable risk factor even in late life,” Ferguson said. “But I wouldn’t say that people have to be worried about this just yet.”

Kaitlin Sullivan is a contributor for NBCNews.com who has worked with NBC News Investigations. She reports on health, science and the environment and is a graduate of the Craig Newmark Graduate School of Journalism at City University of New York.

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Cholesterol: top foods to improve your numbers.

Diet can play an important role in lowering your cholesterol. Here are some foods to improve your cholesterol and protect your heart.

Can a bowl of oatmeal help lower your cholesterol? How about a handful of almonds? A few simple tweaks to your diet — along with exercise and other heart-healthy habits — might help you lower your cholesterol.

Oatmeal, oat bran and high-fiber foods

Oatmeal has soluble fiber, which reduces your low-density lipoprotein (LDL) cholesterol, the "bad" cholesterol. Soluble fiber is also found in such foods as kidney beans, Brussels sprouts, apples and pears.

Soluble fiber can reduce the absorption of cholesterol into your bloodstream. Five to 10 grams or more of soluble fiber a day decreases your LDL cholesterol.

One serving of a breakfast cereal with oatmeal or oat bran provides 3 to 4 grams of fiber. If you add fruit, such as a banana or berries, you'll get even more fiber.

Fish and omega-3 fatty acids

Fatty fish has high levels of omega-3 fatty acids, which can reduce your triglycerides — a type of fat found in blood. These acids also may help lower your blood pressure and risk of developing blood clots. In people who have already had heart attacks, omega-3 fatty acids may reduce the risk of sudden death.

Omega-3 fatty acids don't affect LDL cholesterol levels but may help lower triglycerides and increase HDL , the good cholesterol. But because of those acids' other heart benefits, the American Heart Association recommends eating at least two servings of fish a week. Baking or grilling the fish avoids adding unhealthy fats.

The highest levels of omega-3 fatty acids are in:

Foods such as walnuts, flaxseed and canola oil also have small amounts of omega-3 fatty acids.

Omega-3 and fish oil supplements are available. Talk to your doctor before taking any supplements.

Almonds and other nuts

Almonds and other tree nuts can improve blood cholesterol. Studies have shown that walnuts, which have omega-3 fats, may help protect the heart and lower the risk of heart attack for people who already have heart disease. All nuts are high in calories, so a handful added to a salad or eaten as a snack will do.

Avocados are a good source of nutrients as well as monounsaturated fatty acids (MUFAs). Research suggests that the fiber from avocados can improve HDL cholesterol levels and the quality of LDL cholesterol. Adding two servings of avocado per week to a heart-healthy diet can lower your risk of heart disease.

People tend to think of avocados in guacamole, which often is eaten with high-fat corn chips. Try adding avocado slices to salads and sandwiches or eating them as a side dish. Also try guacamole with raw cut vegetables, such as cucumber slices.

Replacing saturated fats, such as those found in meats, with MUFAs are part of what makes the Mediterranean diet heart healthy.

Try using olive oil in place of other fats in your diet. You can saute vegetables in olive oil, add it to a marinade or mix it with vinegar as a salad dressing. You can also use olive oil as a substitute for butter when basting meat or as a dip for bread. Extra virgin olive oil also reduces the risk of heart attacks.

Foods with added plant sterols or stanols

Sterols and stanols are substances found in plants that help block the absorption of cholesterol. Foods that have been fortified with sterols or stanols are available.

Margarines and orange juice with added plant sterols can help lower LDL cholesterol. Adding 2 grams of sterol to your diet every day can lower your LDL cholesterol by 5% to 15%.

It's not clear whether food with plant sterols or stanols lowers your risk of heart attack or stroke — although experts assume that foods that lower cholesterol do cut the risk. Plant sterols or stanols don't appear to affect levels of triglycerides or of high-density lipoprotein (HDL) cholesterol, the "good" cholesterol.

Whey protein

Whey protein, which is found in dairy products, may account for many of the health benefits attributed to dairy. Studies have shown that whey protein given as a supplement lowers both LDL and total cholesterol as well as blood pressure. You can find whey protein powders in health food stores and some grocery stores.

Other changes to your diet

Getting the full benefit of these foods requires other changes to your diet and lifestyle. One of the most helpful changes is limiting the saturated and trans fats you eat.

Saturated fats — such as those in meat, butter, cheese and other full-fat dairy products — raise your total cholesterol. Decreasing your consumption of saturated fats to less than 7% of your total daily calorie intake can reduce your LDL cholesterol by 8% to 10%.

Trans fats, sometimes listed on food labels as "partially hydrogenated vegetable oil," are often used in margarines and store-bought cookies, crackers and cakes. Trans fats raise overall cholesterol levels. The Food and Drug Administration banned the use of partially hydrogenated vegetable oils in processed foods sold after January 1, 2020.

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Tangney CC, et al. Lipid management with diet or dietary supplements. https://uptodate.com/contents/search. Accessed March 6, 2023.
Your guide to lowering your cholesterol with therapeutic lifestyle changes. National Heart, Lung, and Blood Institute. https://www.nhlbi.nih.gov/health-topics/all-publications-and-resources/your-guide-lowering-cholesterol-therapeutic-lifestyle. Accessed March 8, 2023.
Grundy SM, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Journal of the American College of Cardiology. doi:10.1016/j.jac.2018.11.003.
Prevention and treatment of high cholesterol (hyperlipidemia). American Heart Association. https://www.heart.org/en/health-topics/cholesterol/prevention-and-treatment-of-high-cholesterol-hyperlipidemia. Accessed March 6, 2023.
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Eating an avocado once a week may lower heart disease risk. American Heart Association. https://www.heart.org/en/news/2022/03/30/eating-an-avocado-once-a-week-may-lower-heart-disease-risk. Accessed March 6, 2023.
Amirani E, et al. Effects of whey protein on glycemic control and serum lipoproteins in patients with metabolic syndrome and related conditions: A systematic review and meta-analysis of randomized controlled clinical trials. Lipids in Health and Disease. doi: 10.1186/s12944-020-01384-7.
AskMayoExpert. Hyperlipidemia (adult). Mayo Clinic; 2022.
2020-2025 Dietary Guidelines for Americans. U.S. Department of Health and Human Services and U.S. Department of Agriculture. https://www.dietaryguidelines.gov/. Accessed March 6, 2023.
Final determination regarding regarding partially hydrogenated oils (removing trans fat). U.S. Food and Drug Administration. https://www.fda.gov/food/food-additives-petitions/final-determination-regarding-partially-hydrogenated-oils-removing-trans-fat. Accessed March 6, 2023.
Mozaffarian D, et al. Dietary fat. https://uptodate.com/contents/search. Accessed March 15, 2023.
Mahmassani HA, et al. Avocado consumption and risk factors for heart disease: A systematic review and meta-analysis. The American Journal of Clinical Nutrition. 2018; doi:10.1093/ajcn/nqx078.

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Vision loss and high cholesterol identified as risk factors for dementia

By Rohan Rajeev July 31, 2024

Red blood cells flowing in a vessel was squeezed by two group of yellow balls — in the lab coverage from STAT

U ntreated vision loss and high LDL cholesterol have been added as two new potentially modifiable risk factors for dementia in a report released Wednesday by the Lancet Commission.

These new additions join 12 other risk factors outlined by the commission, affiliated with University College London, in previous reports on dementia prevention, intervention, and care in 2017 and 2020. The other risk factors are lack of education, hypertension, physical inactivity, diabetes, social isolation, excessive alcohol consumption, air pollution, smoking, obesity, traumatic brain injury, and depression.

The commission’s latest findings suggest more ways of preventing dementia than previously known, according to Gill Livingston, a professor of psychiatry at University College London and co-author on the report.

“A lot of surveys have asked people of 50 and above what illnesses they most are concerned about, and dementia tends to come up as the highest one,” Livingston said. “And yet there’s really quite a lot that we can do to change the scales and make it less likely.”

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Avoidable vision loss and blindness are estimated to affect 12.6% of adults aged 50 and older. By conducting a meta-analysis of 14 cohort studies, the commission found a 47% increase in risk for dementia in adults who have untreated vision loss. In another meta-analysis, cataracts and diabetic retinopathy had significant associations with dementia risk.

Follow-up studies in the U.S. found that those who had cataract extractions had significantly reduced risk for dementia — a 29% decrease — opposed to those who did not have cataract extractions. Cataracts are marked by the lens of the eye becoming cloudy, resulting in hazy vision. They can arise with aging and other conditions that cause proteins in the lens to break down and clump together.

Livingston said the role of vision loss as a risk factor for dementia can be compared to the loss of hearing, identified as a risk factor in a previous report.

“One of the ways in which both vision and hearing act is in terms of cognitive stimulation,” Livingston said. “People who have hearing loss have a reduction in the volume of the temporal lobe.”

Maya Koronyo-Hamaoui, a professor of neurosurgery at Cedars-Sinai Medical Center, said the retina is a significant aspect of the link to dementia. It’s the only central nervous system tissue that’s both connected directly to the brain and not shielded by bone, allowing for noninvasive and high-resolution imaging.

“In our cohorts, when we see damage to the retina, there’s almost always the same extent of damage in the brain,” Koronyo-Hamaoui said of her own research.

Molecular changes in the retina affect processes like circadian rhythms — responsible for regulating the sleep-wake cycle — and vision, which Koronyo-Hamaoui believes could potentially mirror damage in the brain.

There’s a social aspect of vision loss that plays into dementia risk, Livingston said.

“People who have these losses go out less, see other people less, are much more likely to become socially isolated,” Livingston said. The report notes that vision loss most often goes untreated in low-income and middle-income countries.

Higher LDL cholesterol — also known as the “bad” cholesterol — was also associated with higher incidence of dementia, the report’s authors found. High total cholesterol and low HDL were also found to be risk factors for dementia in an analysis of 27 studies. LDL is the type of cholesterol responsible for buildup and blockage of arteries, while HDL removes LDL from the bloodstream and carries it back to the liver.

The commission said that individuals with high LDL specifically in midlife, ages 18 to 65, would be at highest risk for dementia.

What’s behind the association between high cholesterol and dementia risk? “Excess brain cholesterol is associated with people having higher amyloid within their brain and also with increased stroke risk,” Livingston explained. Buildup of the sticky protein amyloid is associated with Alzheimer’s, while increased stroke risk is associated with vascular dementia.

Related: New cardiovascular risk model could greatly decrease use of statins and increase heart attacks, study warns

Erin Ferguson, a Ph.D. student and researcher in the department of epidemiology and biostatistics at the University of California, San Francisco, described the research as “very exciting work” because of the prevalence of high cholesterol and statin use in older adults. But she said that the current evidence citing LDL as a risk factor is variable, drawing on what she’s seen in her research at Kaiser Permanente looking at vascular comorbidities of dementia.

“Even looking at ages 55 to 65 in this cohort, I’m not able to see an association between high LDL cholesterol and dementia risk,” Ferguson said of her own research cohort. “I’m a little surprised that LDL was the main cholesterol listed when there’s a whole lot of other evidence showing that HDL may play a factor.” She added that triglycerides, a type of fat that circulates in the blood and stores energy, may also play a role in preventing dementia.

Regulating levels of cholesterol, like lowering LDL, also decreases the chance of cardiovascular events like stroke and heart attack, Ferguson noted. These events, in turn, are risk factors for dementia, namely vascular dementia.

There are several ways to maintain normal cholesterol levels to mitigate dementia risk. The go-to for older adults are statins, according to Ferguson. For younger adults, she suggests exercise and diet to keep LDL levels in check.

This story has been corrected to reflect that the retina is the only central nervous tissue that is both connected to the brain and not shielded by bone.

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New study adds to increasing evidence that sugar substitute erythritol raises cardiovascular risk

by Cleveland Clinic

New Cleveland Clinic research shows that consuming foods with erythritol, a popular artificial sweetener, increases the risk of cardiovascular events such as heart attack and stroke. The findings, from a new intervention study in healthy volunteers, show erythritol made platelets (a type of blood cell) more active, which can raise the risk of blood clots. Sugar (glucose) did not have this effect.

Published in Arteriosclerosis Thrombosis and Vascular Biology , the research adds to increasing evidence that erythritol may not be as safe as currently classified by food regulatory agencies and should be reevaluated as an ingredient. The study was conducted by a team of Cleveland Clinic researchers as part of a series of investigations on the physiological effects of common sugar substitutes.

"Many professional societies and clinicians routinely recommend that people at high cardiovascular risk—those with obesity, diabetes or metabolic syndrome—consume foods that contain sugar substitutes rather than sugar," said senior and corresponding author Stanley Hazen, M.D., Ph.D., chair of Cardiovascular and Metabolic Sciences in Cleveland Clinic's Lerner Research Institute and co-section head of Preventive Cardiology. "These findings underscore the importance of further long-term clinical studies to assess the cardiovascular safety of erythritol and other sugar substitutes."

Erythritol and other artificial sweeteners are common replacements for table sugar in low-calorie, low-carbohydrate and "keto" products. Erythritol is about 70% as sweet as sugar and is produced through fermenting corn. After ingestion, erythritol is poorly metabolized by the body. Instead, it goes into the bloodstream and leaves the body mainly through urine. The human body creates low amounts of erythritol naturally, so any additional consumption can accumulate.

Erythritol is classified by the U.S. Food and Drug Administration and the European Food Safety Authority as a GRAS ("generally recognized as safe") ingredient, allowing its use without restriction in food products. This is primarily because it is a sugar alcohol found naturally in fruits and vegetables and a byproduct of glucose metabolism in human tissue, although in small quantities.

However, recent studies by Dr. Hazen's group have found evidence that erythritol in typically consumed amounts may increase cardiovascular risk.

The current research builds on the team's previous study , published last year in Nature Medicine , which revealed that cardiac patients with high erythritol levels were twice as likely to experience a major cardiac event in the following three years compared to those with low levels. The study also discovered that adding erythritol to patients' blood or platelets increased clot formation. These findings were confirmed by pre-clinical studies.

The new human intervention study was designed to more directly observe the effects on platelets following erythritol ingestion at a dose typically contained in a "sugarless" soda or muffin. In 20 healthy volunteers, researchers found that the average erythritol level after eating increased over 1,000 times in the group that consumed erythritol compared to their initial levels. Results also revealed participants showed a significant increase in blood clot formation after consuming erythritol, but no change was observed after consuming glucose.

"This research raises some concerns that a standard serving of an erythritol-sweetened food or beverage may acutely stimulate a direct clot-forming effect," said study co-author W. H. Wilson Tang, M.D., research director for Heart Failure and Cardiac Transplantation Medicine at Cleveland Clinic. "Erythritol and other sugar alcohols that are commonly used as sugar substitutes should be evaluated for potential long-term health effects, especially when such effects are not seen with glucose itself."

He adds that the results of this study are especially notable because they come on the heels of another recent study by this research group showing that xylitol, another common artificial sweetener, produced similar increases in plasma levels and affected platelet aggregation in healthy volunteers the same way. Like erythritol, studies with xylitol also included large-scale observation studies demonstrating that high xylitol levels are associated with increased risk of heart attack , stroke or death over the following three years.

The authors note that further clinical studies assessing the long-term cardiovascular safety of erythritol are warranted.

"I feel that choosing sugar-sweetened treats occasionally and in small amounts would be preferable to consuming drinks and foods sweetened with these sugar alcohols, especially for people at elevated risk of thrombosis such as those with heart disease, diabetes or metabolic syndrome ," Dr. Hazen advises. "Cardiovascular disease builds over time, and heart disease is the leading cause of death globally. We need to make sure the foods we eat aren't hidden contributors."

The research is part of Dr. Hazen's ongoing investigation into factors that contribute to residual cardiovascular risk. His team follows patients over time and finds chemical signatures in blood that can predict the future development of heart and metabolic disease. He has made pioneering discoveries in atherosclerosis and inflammatory disease research, including the seminal discovery linking gut microbial pathways to cardiovascular disease and metabolic diseases.

Dr. Hazen also directs Cleveland Clinic's Center for Microbiome and Human Health and holds the Jan Bleeksma Chair in Vascular Cell Biology and Atherosclerosis.

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At risk of high cholesterol? Taking fish oil may help

An image of spilled clear-yellow pills on a solid surface

Study finds omega-3 supplements reduce genetic risk of high total cholesterol, LDL and triglyceride levels

Fish oil supplements are a multi-billion dollar industry in the U.S. and abroad, with about two out of every 25 people popping the popular omega-3 pills.

And a new study from the University of Georgia might encourage a new population to start looking into the supplements as well: people with a genetic predisposition to high cholesterol.

Using genetic data from more than 441,000 participants, the researchers calculated a score to predict the genetic likelihood of high levels of total cholesterol, high LDL cholesterol (which is often referred to as “bad” cholesterol), triglycerides and HDL cholesterol (or “good” cholesterol).

Environmental portrait of researcher in front of building

“Recent advances in genetic studies have allowed us to predict someone’s genetic risk of high cholesterol,” said Yitang Sun, a recent doctoral graduate from UGA’s Department of Genetics . “But the current prediction has room for improvement because it does not consider individual differences in lifestyles, such as taking fish oil supplements.”

The researchers found that participants who reported taking fish oil supplements have lower blood lipid levels than predicted, especially for total cholesterol, LDL cholesterol and triglycerides.

“Our study shows that considering lifestyles will improve genetic prediction,” said Kaixiong Ye , corresponding author of the study and an assistant professor of genetics in UGA’s Franklin College of Arts and Sciences . “Our findings also support that fish oil supplements may counteract the genetic predisposition to high cholesterol.”

Fish oil counters effect of family history of high cholesterol

It’s no secret that high cholesterol is bad for the body. Arteries start to harden, and the risk of heart attack or stroke increases.

While a healthy diet and exercise can help prevent it, the Centers for Disease Control and Prevention estimates that more than 86 million American adults — or about one in four — have high cholesterol.

Millions more are at risk of developing high cholesterol due to a variety of factors including one they can’t control: genetics.

Taking fish oil is associated with a shift toward a healthy lipid profile.” —Kaixiong Ye, Franklin College of Arts and Sciences

For people whose families have a history of high cholesterol, the study’s findings offer another possibility to help safeguard their health.

“Taking fish oil is associated with a shift toward a healthy lipid profile,” Ye said.

The researchers also analyzed the effects of fish oil on HDL cholesterol and found the supplements are beneficial in raising the so-called “good” cholesterol.

Published in the American Journal of Clinical Nutrition, the study was led by Yitang Sun , a doctoral student in UGA’s Department of Genetics . Additional co-authors include Tryggvi McDonald, Abigail Baur, Huifang Xu and Naveen Brahman Bateman, of UGA’s Franklin College; Ye Shen of UGA’s College of Public Health ; and Changwei Li, of Tulane University.

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