No link between milk and increased cholesterol according to new study of 2 million people

by University of Reading

Credit: Pixabay/CC0 Public Domain

Regular consumption of milk is not associated with increased levels of cholesterol, according to new research.

25 may 2021--A study published in the International Journal of Obesity looked at three large population studies and found that people who regularly drank high amounts of milk had lower levels of both good and bad cholesterol, although their BMI levels were higher than non-milk drinkers. Further analysis of other large studies also suggests that those who regularly consumed milk had a 14% lower risk of coronary heart disease.

The team of researchers took a genetic approach to milk consumption by looking at a variation in the lactase gene associated with digestion of milk sugars known as lactose.

The study identified that having the genetic variation where people can digest lactose was a good way for identifying people who consumed higher levels of milk.

Prof Vimal Karani, Professor of Nutrigenetics and Nutrigenomics at the University of Reading said:

"We found that among participants with a genetic variation that we associated with higher milk intake, they had higher BMI, body fat, but importantly had lower levels of good and bad cholesterol. We also found that those with the genetic variation had a significantly lower risk of coronary heart disease. All of this suggests that reducing the intake of milk might not be necessary for preventing cardiovascular diseases."

The new research was conducted following several contradictory studies that have previously investigated the causal link between higher dairy intake and cardiometabolic diseases such as obesity and diabetes. To account for inconsistencies in sampling size, ethnicity and other factors, the team conducted a meta-analysis of data in up to 1.9 million people and used the genetic approach to avoid confounding.

Even though the UK biobank data showed that those with the lactase genetic variation had 11% lower risk of type 2 diabetes, the study did not suggest that there is any strong evidence for a link between higher milk intake and increased likelihood of diabetes or its related traits such as glucose and inflammatory biomarkers.

Professor Karani said:

"The study certainly shows that milk consumption is not a significant issue for cardiovascular disease risk even though there was a small rise in BMI and body fat among milk drinkers. What we do note in the study is that it remains unclear whether it is the fat content in dairy products that is contributing to the lower cholesterol levels or it is due to an unknown 'milk factor'".

More information: Karani Santhanakrishnan Vimaleswaran et al, Evidence for a causal association between milk intake and cardiometabolic disease outcomes using a two-sample Mendelian Randomization analysis in up to 1,904,220 individuals, International Journal of Obesity (2021). DOI: 10.1038/s41366-021-00841-2

Provided by University of Reading 

3 things to know about cholesterol

With the release of new guidelines for treating and managing cholesterol, there may be questions not only about the changes in the update, but about cholesterol itself.
Most people know that high cholesterol is bad. But there's a bigger picture involved when determining what's considered too high. Put another way, the same number could be in the normal range for one person but considered high for another.

13 nov 2018--The only way to know your cholesterol situation and, more importantly, what to do about it, is by working with a health care provider. This is important because poorly managed cholesterol could lead to heart attack, stroke and other major health problems.
Here are the basics needed to understand, treat and manage cholesterol.

What is cholesterol?

"First of all, it's important for people to understand that cholesterol is itself not a bad thing," said Dr. Robert Eckel, director of the Lipid Clinic at University of Colorado Hospital. "Cholesterol is an important part of the body that every cell has on its surface. But in our bloodstream, we don't want too much and the vehicle that carries it can be important."
Cholesterol is a waxy substance the body uses to build cells. The liver makes all the cholesterol the body needs. However, dietary cholesterol the kind from food and some drinks such as milk causes the liver to send even more cholesterol into the bloodstream.
Cholesterol is carried in the blood in the form of high-density lipoproteins (HDL)—the "good" kind—and low-density lipoproteins (LDL)—the "bad" kind. And that's where treatment is emphasized.
The bad kind of cholesterol can collect in the artery walls, eventually causing stiffness and narrowing. This is atherosclerosis, which can be the basis of a heart attack or stroke.
Good cholesterol helps by removing the bad, although that's not easy to do. HDL can only help in the fight, not win it.
"HDL is not something we try to alter with medication. It's important in predicting risk but changing it is best done via lifestyle changes," said Eckel, who was part of the team that created cholesterol guidelines from the American Heart Association, American College of Cardiology and other health organizations in 2013. Those guidelines were updated Saturday.
The total cholesterol figure is based on HDL, LDL and a third factor: triglycerides. Triglycerides not only circulate in blood but are the most common type of fat in the body. A high triglyceride level combined with high LDL or low HDL cholesterol is linked to those fatty buildups within the artery walls that increase the risk of heart attack and stroke.

What do cholesterol numbers mean?

Cholesterol numbers mean different things for each person's situation.
"There are a lot of factors that enter into the determination of the best level for each individual. For instance, someone in their 40s and 50s the LDL cholesterol may be slightly elevated, but the person might have no other risk factors," Eckel said.
Dr. Scott M. Grundy, chairman of the writing committee for the new cholesterol guidelines, notes that when doctors are working out an action plan with their patients, they should consider a person's "risk-enhancing factors" such as family history, kidney disease or other personal scenarios.
"These are important," said Grundy, a professor of internal medicine at the University of Texas Southwestern Medical Center and Veterans Affairs Medical Center in Dallas. "Patients should be aware of these and work to determine how to think about them with their doctor."

How is elevated or high cholesterol treated?

Treatment comes in two forms: lifestyle changes and medication.
"We always want people to start with making lifestyle changes," Eckel said. "That means eating a diet low in saturated fat and trans fats, and enriched with fruits and vegetables, whole grains, legumes, lean meat, fish and nuts. Another lifestyle change is being physically more active."
If that sounds like a plan for losing excess weight and keeping it off, that's exactly the point. A healthy body weight helps reduce LDL levels and helps people with normal cholesterol levels stay that way.
Sometimes, diet and exercise alone are enough to get numbers into the comfort zone. Sometimes, they're not. For those people, the next option is usually taking a cholesterol-lowering medication called a statin.
"This is a very well-proven, evidence-based option," Eckel said. "A lot of clinical trials strongly support taking statins."
The type of statin and dose can vary from person to person. In some cases, doctors may prescribe other or additional medications that are not statins, such as ezetimibe or a PCSK9 inhibitor.
"The neat thing about cholesterol-lowering plans is that you can see changes quite quickly," Eckel said, noting that cholesterol levels can improve within weeks of diet changes or medications.

Process that turns 'good cholesterol' bad discovered

Cleveland Clinic researchers have discovered the process by which high-density lipoprotein (HDL) – the so-called "good cholesterol" – becomes dysfunctional, loses its cardio-protective properties, and instead promotes inflammation and atherosclerosis, or the clogging and hardening of the arteries. Their research was published online today in the journalNature Medicine.

27 jan 2014--The beneficial and cardio-protective properties of HDL have been studied and reported extensively, yet all clinical trials of pharmaceuticals designed to raise HDL levels have so far failed to show that they significantly improve cardiovascular health. This disconnect, as well as recent research showing that a protein abundant in HDL is present in an oxidized form in diseased artery walls, spurred the research team – led by Stanley Hazen, M.D., Ph.D., Vice Chair of Translational Research for the Lerner Research Institute and section head of Preventive Cardiology & Rehabilitation in the Miller Family Heart and Vascular Institute at Cleveland Clinic – to study the process by which HDL becomes dysfunctional.

Apolipoprotein A1 (apoA1) is the primary protein present in HDL, providing the structure of the molecule that allows it to transfer cholesterol out of the artery wall and deliver it to the liver, from which cholesterol is excreted. It's apoA1 that normally gives HDL its cardio-protective qualities, but Dr. Hazen and his colleagues have discovered that in the artery wall during atherosclerosis, a large proportion of apoA1 becomes oxidized and no longer contributes to cardiovascular health, but rather, contributes to the development of coronary artery disease.

Over the course of more than five years, Dr. Hazen and his colleagues developed a method for identifying dysfunctional apoA1/HDL and discovered the process by which it is oxidized and turned dysfunctional in the artery wall. They then tested the blood of 627 Cleveland Clinic cardiology patients for the dysfunctional HDL and found that higher levels raised the patient's risk for cardiovascular disease.

"Identifying the structure of dysfunctional apoA1 and the process by which it becomes disease-promoting instead of disease-preventing is the first step in creating new tests and treatments for cardiovascular disease," said Dr. Hazen. "Now that we know what this dysfunctional protein looks like, we are developing a clinical test to measure its levels in the bloodstream, which will be a valuable tool for both assessingcardiovascular disease risk in patients and for guiding development of HDL-targeted therapies to prevent disease."

The research also points toward new therapeutic targets for pharmaceuticals, such as those designed to prevent the formation of dysfunctional HDL and the development or progression of atherosclerosis.

More information: An abundant dysfunctional apolipoprotein A1 in human atheroma, DOI: 10.1038/nm.3459

Provided by Cleveland Clinic

Cholesterol guidelines are based on strong, evidence-based science, AHA says

The American Heart Association and American College of Cardiology vigorously defend the recently published risk assessment and cholesterol guidelines despite recent media reports critical of the risk assessment calculator tool.

20 nov 2013--"We stand behind our guidelines, the process that was used to create them and the degree to which they were rigorously reviewed by experts," said Mariell Jessup, M.D., president of the American Heart Association.

The risk calculator provides an estimate of a patient's ten year risk of having a heart attack or stroke, and is one component that healthcare providers should use as they discuss whether or not a patient would benefit from a statin drug, a type of medication that lowers artery-clogging LDL cholesterol. The guidelines and risk assessment tool are developed from, and based on, the best evidence available as determined by the expert panel. Authors say the risk assessment tool is intended to spark a conversation between patients and their physician to help drive individualized care based on that patient's health profile.

"Clinical practice guidelines such as these should not take the place of sound clinical judgment. These guidelines should enable a discussion between a patient and their healthcare provider about the best way to prevent a heart attack or stroke, based on the patient's personal health profile and their preferences. The risk calculator score is part of that discussion, because it provides specific information to the patient about their personal health. A high score does not automatically mean a patient should be taking a statin drug" said John Gordon Harold, M.D, president of the American College of Cardiology.

Harold adds the risk assessment is a significant improvement over the previous model. For the first time in a major guideline, it focuses on estimating risk for both heart attacks AND strokes, whereas previous guidelines only focused on heart attack risk. The guidelines also provide estimates applicable to African Americans for the first time ever.

One in three Americans die of cardiovascular diseases such as heart attacks, heart failure and stroke. Strong scientific evidence indicates that statins are a reasonable treatment approach for a large majority of patients, and can help people avoid a heart attack or stroke even if their risk is as low as five percent.

At the invitation of the National Heart, Lung, and Blood Institute (NHLBI), The American Heart Association and the American College of Cardiology assumed the joint governance, management and public distribution of four clinical practice guidelines focused on cardiovascular prevention. Other guidelines, published at the same time address obesity, healthy lifestyle and risk assessment.

The groups published the new guidelines November 12th in the American Heart Association's journal Circulation and the Journal of the American College of Cardiology.

Provided by American Heart Association

ACC/AHA publish new guideline for management of blood cholesterol

The American College of Cardiology and the American Heart Association today released a new clinical practice guideline for the treatment of blood cholesterol in people at high risk for cardiovascular diseases caused by atherosclerosis, or hardening and narrowing of the arteries, that can lead to heart attack, stroke or death.

13 nov 2013--The guideline identifies four major groups of patients for whom cholesterol-lowering HMG-CoA reductase inhibitors, or statins, have the greatest chance of preventing stroke and heart attacks. The guideline also emphasizes the importance of adopting a heart-healthy lifestyle to prevent and control high blood cholesterol.

"The new guideline uses the highest quality scientific evidence to focus treatment of blood cholesterol on those likely to benefit most," said Neil J. Stone, MD, Bonow professor of medicine at Northwestern University Feinberg School of Medicine and chair of the expert panel that wrote the new guideline. "This guideline represents a departure from previous guidelines because it doesn't focus on specific target levels of low-density lipoprotein cholesterol, commonly known as LDL, or 'bad cholesterol,' although the definition of optimal LDL cholesterol has not changed. Instead, it focuses on defining groups for whom LDL lowering is proven to be most beneficial."

The new guideline recommends moderate- or high-intensity statin therapy for these four groups:

• Patients who have cardiovascular disease;
• Patients with an LDL, or "bad" cholesterol level of 190 mg/dL or higher;
• Patients with Type 2 diabetes who are between 40 and 75 years of age; and
• Patients with an estimated 10-year risk of cardiovascular disease of 7.5 percent or higher who are between 40 and 75 years of age (the report provides formulas for calculating 10-year risk).

In terms of clinical practice, physicians can use risk assessment tools in some cases to determine which patients would most likely benefit from statin therapy, rather than focusing only on blood cholesterol to determine which patients would benefit.

"The likely impact of the recommendations is that more people who would benefit from statins are going to be on them, while fewer people who wouldn't benefit from statins are going to be on them," Dr. Stone said. Doctors may also consider switching some patients to a higher dose of statins to derive greater benefit as a result of the new guidelines.

The guideline was prepared by a panel of experts based on an analysis of the results of randomized controlled trials. The panel was charged with guiding the optimal treatment of blood cholesterol to address the rising rate of cardiovascular disease, currently the leading cause of death and disability in the U.S.

The panel chose to focus on the use of statins after a detailed review of other cholesterol-lowering drugs. "Statins were chosen because their use has resulted in the greatest benefit and the lowest rates of safety issues. No other cholesterol-lowering drug is as effective as statins," said Dr. Stone. He added that there is a role for other cholesterol-lowering drugs, for example, in patients who suffer side effects from statins.

The report also stresses the importance of lifestyle in managing cholesterol and preventing heart disease. "The cornerstone of all guidelines dealing with cholesterol is a healthy lifestyle," said Dr. Stone. "That is particularly important in the young, because preventing high cholesterol later in life is the first and best thing someone can do to remain heart-healthy. On the other hand, if someone already has atherosclerosis, lifestyle changes alone are not likely to be enough to prevent heart attack, stroke, and death, and statin therapy will be necessary."

In addition to identifying patients most likely to benefit from statins, the guideline outlines the recommended intensity of statin therapy for different patient groups. Rather than use a "lowest is best" approach that combines a low dose of a statin drug along with several other cholesterol-lowering drugs, the panel found that it can be preferable to focus instead on a healthy lifestyle along with a higher dose of statins, eliminating the need for additional medications.

"The focus for years has been on getting the LDL low," said Dr. Stone. "Our guidelines are not against that. We're simply saying how you get the LDL low is important. Considering all the possible treatments, we recommend a heart-healthy lifestyle and statin therapy for the best chance of reducing your risk of stroke or heart attack in the next 10 years."

The guidelines are intended to serve as a starting point for clinicians. Some patients who do not fall into the four major categories may also benefit from statin therapy, a decision that will need to be made on a case-by-case basis. The expert panel that wrote the report was convened by the National Heart, Lung, and Blood Institute of the National Institutes of Health. At the invitation of the NHLBI, the American Heart Association and American College of Cardiology assumed the joint governance, management and publication of this guideline, along with four other prevention guidelines, in June. Committee members volunteered their time and were required to disclose all healthcare-related relationships, including those existing one year before the initiation of the writing project.

More information: The full text of the report, "2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults," will be published in future print issues of the of the Journal of the American College of Cardiology and the American Heart Association's journal Circulation. It will also be accessible today on the ACC website and AHA.

Provided by American College of Cardiology

Super-sticky 'ultra-bad' cholesterol revealed in people at high risk of heart disease

Scientists from the University of Warwick have discovered why a newly found form of cholesterol seems to be 'ultra-bad', leading to increased risk of heart disease. The discovery could lead to new treatments to prevent heart disease particularly in people with type 2 diabetes and the elderly.

31 may 2011--The research, funded by the British Heart Foundation (BHF), found that 'ultrabad' cholesterol, called MGmin-low-density lipoprotein (LDL), which is more common in people with type 2 diabetes and the elderly, appears to be 'stickier' than normal LDL. This makes it more likely to attach to the walls of arteries. When LDL attaches to artery walls it helps form the dangerous 'fatty' plaques' that cause coronary heart disease (CHD).

CHD is the condition behind heart attacks, claiming 88,000 lives in the UK every year (1).

The researchers made the discovery by creating human MGmin-LDL in the laboratory, then studying its characteristics and interactions with other important molecules in the body.

They found that MGmin-LDL is created by the addition of sugar groups to 'normal' LDL – a process called glycation – making LDL smaller and denser. By changing its shape, the sugar groups expose new regions on the surface of the LDL. These exposed regions are more likely to stick to artery walls, helping to build fatty plaques. As fatty plaques grow they narrow arteries - reducing blood flow - and they can eventually rupture, triggering a blood clot that causes a heart attack or stroke.

The discovery might also explain why metformin, a widely prescribed type 2 diabetes drug, seems to lead to reduced heart disease risk. Metformin is known to lower blood sugar levels, and this new research shows it may reduce the risk of CHD by blocking the transformation of normal LDL to the more 'sticky' MGmin-LDL.

Dr Naila Rabbani, Associate Professor of Experimental Systems Biology at Warwick Medical School, who led the study, said:

"We're excited to see our research leading to a greater understanding of this type of cholesterol, which seems to contribute to heart disease in diabetics and elderly people. Type 2 diabetes is a big issue – of the 2.6 million diabetics in the UK, around 90 per cent have type 2. It's also particularly common in lower income groups and South Asian communities. (2, 3)

"The next challenge is to tackle this more dangerous type of cholesterol with treatments that could help neutralise its harmful effects on patients' arteries."

Dr Shannon Amoils, Research Advisor at the BHF, which funded the study, said:

"We've known for a long time that people with diabetes are at greater risk of heart attack and stroke. There is still more work to be done to untangle why this is the case, but this study is an important step in the right direction.

"This study shows how the make-up and the shape of a type of LDL cholesterol found in diabetics could make it more harmful than other types of LDL. The findings provide one possible explanation for the increased risk of coronary heart disease in people with diabetes.

"Understanding exactly how 'ultrabad' LDL damages arteries is crucial, as this knowledge could help develop new anti-cholesterol treatments for patients."

The research was published in the journal Diabetes.

Low cholesterol may be sign of undiagnosed cancer

04 nov 2009– Low total cholesterol may be a sign of cancer rather than a cause, as some researchers have suggested, and men who have low cholesterol actually have a lower risk of developing high-risk prostate cancer, two teams reported on Tuesday.

Both studies, reported in the journal Cancer Epidemiology, Biomarkers & Prevention, shed new light on the role of cholesterol and cancer.

For years, researchers had noticed that people who have lower total cholesterol -- a combination of both low-density lipoprotein or LDL, the "bad" kind, and high-density lipoprotein or HDL, the "good" kind -- appeared more likely to have certain types of cancers than other people.

That was worrisome because having low cholesterol, and particularly low levels of "bad" LDL cholesterol, has been shown to protect against heart attacks and strokes.

"Our study affirms that lower total cholesterol may be caused by undiagnosed cancer," Dr. Demetrius Albanes, a senior investigator at the National Cancer Institute, part of the National Institutes of Health, said in a statement.

"In terms of a public health message, we found that higher levels of 'good' cholesterol seem to be protective for all cancers," he said.

The 18-year study of nearly 30,000 Finnish male smokers is the largest and longest of its kind. During that period, 7,545 men developed cancer.

The men with lower total cholesterol levels -- below 230 milligrams/deciliter -- had an 18 percent higher risk of cancer overall -- just as in earlier studies.

But, when they excluded cancers that occurred in the first nine years of the study, this risk disappears.

"This finding supports the idea that the lower serum total cholesterol level we detected as a possible cancer risk factor may actually have been the result of undiagnosed cancers," Albanes told reporters in a telephone briefing.

They also found men who had higher levels of HDL or "good" cholesterol (above 40 milligrams/deciliter) had a 14 percent lower risk of cancer even after excluding nine years of early cases.

MORE STUDIES NEEDED

Albanes said the notion that high levels of HDL may protect against cancer is new and needs to be confirmed in other studies, particularly among women.

"The results should help dispel any lingering concerns anyone might have that having low cholesterol could cause cancer," Eric Jacobs of the American Cancer Society told reporters.

A companion study of more than 5,000 U.S. men by Elizabeth Platz of Johns Hopkins University in Baltimore and colleagues found a link between low cholesterol and a lower risk of high-grade prostate cancer among 5,586 men over 55.

They found that if men had total cholesterol of less than 200 milligrams/deciliter, they had a nearly 60 percent lower risk of developing high grade prostate cancer, the riskiest kind.

It is not clear whether taking cholesterol-lowering statin drugs might help men with prostate cancer. That would need to be studied, Platz said.

Lowering your cholesterol may decrease your risk of cancer

Boston, MA, 24 feb 2009-- — Current research suggests that lowering cholesterol may block the growth of prostate tumors. The related report by Solomon et al, "Ezetimibe Is an Inhibitor of Tumor Angiogenesis," appears in the March 2009 issue of The American Journal of Pathology.
High cholesterol not only leads to atherosclerosis and heart disease, but may also contribute to cancer growth and progression. Prostate cancer is the most common non-skin cancer in the United States, affecting approximately 1 in 6 men. Prostate tumors accumulate high levels of cholesterol, and tumor incidence correlates with eating a high fat/high cholesterol diet "Western" diet. In addition, prostate tumor progression has been linked to serum cholesterol levels.
To examine the role of high cholesterol in prostate cancer, Dr. Keith Solomon and colleagues fed mice a high fat/high cholesterol "Western" diet. They found that high cholesterol levels promoted tumor growth and that Ezetimibe (Zetia™), which blocks the absorption of cholesterol from the intestine, could prevent this increased tumor growth. Ezetimibe also blocked a cholesterol-mediated increase in angiogenesis, the growth of new blood vessels required for tumor progression. These data suggest that reducing cholesterol levels may inhibit prostate cancer growth specifically by inhibiting tumor angiogenesis.
The article from Solomon et al suggests "that cholesterol reduction, which is routinely accomplished pharmacologically in humans, may reduce angiogenesis, ultimately leading to less aggressive tumors." "Lowering cholesterol levels whether through diet, exercise, or the use of safe cholesterol-lowering drugs is known to provide a substantial benefit to patients—in the future it may be possible to add reduced risk of serious prostate cancer to that list of benefits" says Solomon. "We are in the process of working with clinicians to translate these findings into potential human studies. If we can demonstrate the effects noted in our pre-clinical studies in human patients we may be save lives and improve the quality of life," adds Dr. Michael Freeman, senior author of the study.
###
This work was supported by grants from the National Institutes of Health and the US Army Department of Defense.
Solomon KR, Pelton K, Boucher K, Joo J, Tully C, Zurakowski D, Schaffner CP, Kim J, Freeman MR: Ezetimibe Is an Inhibitor of Tumor Angiogenesis. Am J Pathol 2009 174: 1017-1026
For press copies of the articles, please contact Dr. Angela Colmone at 301-634-7953 or acolmone@asip.org.

Longer sleep tied to worse cholesterol in seniors

NEW YORK,09 jan 2009-- Older people who spend more time sleeping have higher cholesterol levels, and less "good" HDL cholesterol, Dutch researchers report.

People who sleep fewer than seven hours a night, as well as those who log more than eight hours may be more likely to develop heart disease, although it's not clear why, Dr. Julia F. van den Berg of Erasmus Medical Center in Rotterdam and colleagues note in the medical journal Psychosomatic Medicine.

To investigate whether cholesterol might be a factor, van den Berg and her team compared sleep duration and total cholesterol levels, as well as the ratio of total to HDL cholesterol, in 768 men and women 57 to 97 years old.

The researchers used actigraphy to measure sleep duration, which involves using a wristwatch-like device to keep track of movement and has been shown to be a more reliable gauge of sleep time than a person's own report. People wore the device for five to seven days and nights.

None of the study participants used cholesterol-lowering drugs.

Overall, van den Berg's team found, people who slept longer had higher cholesterol levels. Among people younger than 65, spending a longer time in bed accounted for most of the relationship. For people 70 and older, the relationship was largely due to the fact that people with more fragmented sleep -- and therefore less sleep time -- had lower cholesterol levels.

It's possible that people who spend more time in bed may be less active, and hence have higher cholesterol levels, the researchers note, but the link between fragmented sleep and low cholesterol is more difficult to explain; underlying illness could be a possibility.

SOURCE: Psychosomatic Medicine, November/December 2008.

Caffeine May Protect Blood-Brain Barrier from Cholesterol Damage

GRAND FORKS, N.D., April 4 -- A daily dose of caffeine broke the link between hypercholesterolemia and Alzheimer's disease in a rabbit model.
After 12 weeks on a high-fat diet, animals given the equivalent of a single cup of coffee a day had a more intact blood-brain barrier compared with animals that did not receive caffeine, Jonathan D. Geiger, Ph.D., of the University of North Dakota, and colleagues, reported in the April issue of the Journal of Neuroinflammation.
"High levels of cholesterol are a risk factor for Alzheimer's disease, perhaps by compromising the protective nature of the blood-brain barrier," said Dr. Geiger. "For the first time we have shown that chronic ingestion of caffeine protects the blood-brain barrier from cholesterol-induced leakage."
A spokesperson for the Alzheimer's Association said the relationship between hypercholesterolemia and Alzheimer's disease remains unclear, as is the contribution of a leaky blood-brain barrier to the disease process.
Sam Gandy, M.D., Ph.D., chair of the National Medical and Scientific Advisory Council for the association and an Alzheimer's researcher at Mount Sinai School of Medicine in New York, also noted that the preclinical model used in the study has not been validated in Alzheimer's disease.
Epidemiologic and experimental studies have suggested that chronic administration of caffeine has beneficial effects for a number of neurovascular disorders, including Alzheimers' disease.
To test their theory that caffeine might counter cholesterol's disruption of the blood-brain barrier, the researchers compared the effects of chronic caffeine administration in rabbits fed a cholesterol-enriched diet or a standard diet.
The daily caffeine dose was 3 mg, administered in the animals' drinking water.
After 12 weeks, the authors examined the animals' olfactory bulbs for evidence of blood-brain barrier leakage and tight junction protein expression levels, activation of astrocytes, and microglia density.
They chose the olfactory bulb because of its intact blood-brain barrier and because olfactory dysfunction is common in Alzheimer's patients and may be one of the earliest signs of the disease.
Blood-brain barrier leakage was assessed by changes in the immunoreactivity of IgG and fibrinogen.
The cholesterol-enriched diet markedly increased IgG and fibrinogen extravasation. Daily caffeine administration blocked that extravasation.
In contrast, caffeine had no effect on IgG and fibrinogen extravasation in animals fed the control diet.
"Chronic ingestion of caffeine protects against high cholesterol diet-induced increases in disruptions of the blood-brain barrier, and caffeine and drugs similar to caffeine might be useful in the treatment of Alzheimer's disease," the authors concluded.
Acknowledging that a leaky blood-brain barrier "is probably not a good thing," Dr. Gandy said the study's relevance to clinical Alzheimer's is unclear.
"These are interesting animal data that merit extension to humans to determine relevance," he said. "Any relationship between cholesterol, blood-brain barrier, and Alzheimer's at this point remains intriguing but speculative."
Dr. Geiger and co-authors reported no disclosures.
Additional source: Journal of NeuroinflammationSource reference: Chen X, et al "Caffeine blocks disruption of blood brain barrier in a rabbit model of Alzheimer's disease" J Neuroinflammation 2008; 5: 12.

Cholesterol as a Danger Has Skeptics

By ALEX BERENSON
For decades, the theory that lowering cholesterol is always beneficial has been a core principle of cardiology. It has been accepted by doctors and used by drug makers to win quick approval for new medicines to reduce cholesterol.
But now some prominent cardiologists say the results of two recent clinical trials have raised serious questions about that theory — and the value of two widely used cholesterol-lowering medicines, Zetia and its sister drug, Vytorin. Other new cholesterol-fighting drugs, including one that Merck hopes to begin selling this year, may also require closer scrutiny, they say.
“The idea that you’re just going to lower LDL and people are going to get better, that’s too simplistic, much too simplistic,” said Dr. Eric J. Topol, a cardiologist and director of the Scripps Translational Science Institute in La Jolla, Calif. LDL, or low-density lipoprotein, is the so-called bad cholesterol, in contrast to high-density lipoprotein, or HDL.
For patients and drug companies, the stakes are enormous. Led by best sellers like Lipitor from Pfizer, cholesterol-lowering medicines, taken by tens of millions of patients daily, are the largest drug category worldwide, with annual sales of $40 billion.
Despite widespread use of the drugs, though, heart disease remains the biggest killer in the United States and other industrialized nations, and many people still have cholesterol levels far higher than doctors recommend.
As a result, drug companies are investing billions of dollars in experimental new cholesterol-lowering medicines that may eventually be used alongside the existing drugs. If the new questions result in slower approvals, it would be yet another handicap for the drug industry.
Because the link between excessive LDL cholesterol and cardiovascular disease has been so widely accepted, the Food and Drug Administration generally has not required drug companies to prove that cholesterol medicines actually reduce heart attacks before approval.
They have not had to conduct so-called outcome or events trials beforehand, which are expensive studies that involve thousands of patients and track whether episodes like heart attacks are reduced.
So far, proof that a drug lowers LDL cholesterol has generally been enough to lead to approval. Only then does the drug’s maker begin an events trial. And until the results of that trial are available, a process that can take several years, doctors and patients must accept the medicine’s benefits largely on faith.
“You’ve got a huge chasm between F.D.A. licensure and a clinical events trial,” said Dr. Allen J. Taylor, the chief of cardiology at Walter Reed Army Medical Center.
Nonetheless, the multistep process has worked well for several cholesterol drugs — including Lipitor and Zocor, which are in a class of drugs known as statins. In those cases, the postapproval trials confirmed that the drugs reduce heart attacks and strokes, adding to confidence about the link between cholesterol and heart disease.
Doctors generally believe that the amount by which cholesterol is lowered, not the method of lowering it, is what matters.
That continues to be the assumption of Dr. Scott M. Grundy, a professor of medicine at the University of Texas Southwestern Medical Center who was the chairman of a panel in 2001 that set national guidelines for cholesterol treatment.
“LDL lowering, however it occurs, delays development of coronary atherosclerosis and reduces risk for heart attack,” Dr. Grundy said this week. In atherosclerosis, plaque builds up in the arteries, eventually leading to blood clots and other problems that cause heart attacks and strokes.
In the last 13 months, however, the failures of two important clinical trials have thrown that hypothesis into question.
First, Pfizer stopped development of its experimental cholesterol drug torcetrapib in December 2006, when a trial involving 15,000 patients showed that the medicine caused heart attacks and strokes. That trial — somewhat unusual in that it was conducted before Pfizer sought F.D.A. approval — also showed that torcetrapib lowered LDL cholesterol while raising HDL, or good cholesterol.
Torcetrapib’s failure, Dr. Taylor said, shows that lowering cholesterol alone does not prove a drug will benefit patients.
Then, on Monday, Merck and Schering-Plough announced that Vytorin, which combines Zetia with Zocor, had failed to reduce the growth of fatty arterial plaque in a trial of 720 patients. In fact, patients taking Vytorin actually had more plaque growth than those who took Zocor alone.
Despite those drawbacks, that trial, called Enhance, also showed that patients on Vytorin had lower LDL levels than those on Zocor alone. For the second time in just over a year, a clinical trial found that LDL reduction did not translate into measurable medical benefits.
The Enhance trial was not an events trial and was not intended to study whether Zetia or Vytorin were effective at reducing heart attacks. But the growth of fatty plaque is closely correlated with heart attacks and strokes.
Without data from events trials for Zetia and Vytorin, no one can be certain if the drugs help or hurt patients. But Merck and Schering did not begin an events trial for the drugs until 2006, nearly four years after the F.D.A. approved Zetia. That trial will not be completed until 2011.
Dr. Robert M. Califf, the vice chancellor for clinical research at Duke University, and a co-lead investigator on the Zetia trial still under way, said companies should have started the trials more quickly. “Outcome trials ought to start when you know you’re going to get on the market,” he said.
On Tuesday, the American Heart Association called for the Zetia outcome trial to be completed as quickly as possible.
Merck has asked the F.D.A. to approve its drug Cordaptive, which raises HDL cholesterol and lowers LDL, without waiting for the results of an events trial. Merck has begun an events trial for Cordaptive, but data will not be available until 2013.
Merck has submitted the application for Cordaptive and has said it expects an answer from the F.D.A. before July. Doctors, patients and the drug industry will be waiting to see whether regulators are still willing to accept the theory that lower cholesterol is always a good thing.

Study links low cholesterol levels and cancer

2 hours, 45 minutes ago
The heart benefits of taking so-called statin drugs to reduce cholesterol might be offset by a slightly increased risk of cancer, although the evidence is by no means clear, U.S. scientists said on Tuesday.
A new pooled, or meta, analysis of past studies involving 41,000 patients on statins found one additional incident of cancer per 1,000 patients with low levels of LDL, or "bad" cholesterol, compared to those with higher LDL.
The results will be published in the July 31 issue of the Journal of the American College of Cardiology.
Dr Richard Karas, professor of medicine at Tufts University School of Medicine in Boston, who led the research, stressed the association did not prove statins caused the increase in cancer risk.
"The demonstrated benefits of statins in lowering the risk of heart disease remain clear; however, certain aspects of lowering LDL with statins remain controversial and merit further research," he said in a statement.
The analysis looked at clinical trials published before November 2005 and involved patients treated with popular statins, including Pfizer Inc.'s Lipitor and Merck & Co. Inc.'s Zocor, which is now off patent.
It did not include data from recently launched statins such as AstraZeneca Plc's Crestor and Merck/Schering-Plough Corp.'s Vytorin.
Dr John C. La Rosa of the State University of New York Downstate Medical Center in Brooklyn, who wrote an accompanying editorial in the journal, said the new research needed to be seen in perspective.
"These current findings provide insufficient evidence that there is any problem with LDL lowering that outweighs its significant benefits on vascular disease," he said.
One possibility is that the higher cancer risk in patients with low LDL reflects the fact they live longer and are therefore more likely to develop cancer.

Why Aerobic Exercise Is Good For The Heart

Aerobic exercise is widely recognized to reduce the risk of coronary heart disease, but until now, researchers have not fully understood the biological mechanisms behind the effect of exercise on cardiovascular health. Findings of a new study show how exercise decreases inflammation, which reduces the risk of atherosclerosis – fatty build-ups in the arteries – that cause most cases of heart disease.
In a study led by Richard P. Sloan, Ph.D., professor of behavioral medicine at Columbia University Medical Center, whole blood samples were taken from 46 healthy young adults (20-45 years old) both before and after participating in moderate or high intensity aerobic exercise, over a 12-week period.
The blood samples were stimulated with the infectious agent lipopolysaccharide (LPS) – gram negative bacteria – and then analyzed for levels of tumor necrosis factor (TNF) – an initial step in the inflammatory cascade. Substantially lower levels of TNF were found after aerobic training, in both the moderate and high intensity groups.
http://www.sciencedaily.com/releases/2007/03/070320073101.htm

Mid-life cholesterol dip may signal mental decline

NEW YORK (Reuters Health) - While a high total cholesterol level in middle age is a risk factor for developing dementia later in life, a drop in cholesterol after middle age may also be a sign of later cognitive problems, a study shows.
It hints that falling total cholesterol levels after middle age may point to an ongoing disease processes in the brain, and could be a marker for risk of late-life cognitive impairment.
Dr. Miia Kivipelto, from the Aging Research Center at the Karolinska Institute in Stockholm, Sweden, and colleagues investigated changes in total cholesterol levels in relation to cognitive functioning in late-life.
The study involved some 2000 people who had their cholesterol level measured in midlife, and were re-examined an average of 21 years later.
The team focused on 70 people who developed mild cognitive impairment during follow-up, 48 who developed Alzheimer's disease and a "control" group of 1,203 people who remained mentally intact.
http://today.reuters.com/news/articlenews.aspx?type=healthNews&storyid=2007-03-16T154712Z_01_COL656553_RTRUKOC_0_US-CHOLESTEROL-DIP.xml&src=rss