Researchers Find New Way to Clear Cholesterol From the Blood
Gerald Hurowitz, M.D.·Published 11 April 2013·11 min read
Key points
Researchers at the University of Michigan have identified a new potential therapeutic target for lowering cholesterol that could be an alternative or complementary therapy to statins.
Research suggests that increasing soluble fiber intake by 5 to 10 grams each day may result in a 5 percent drop in LDL cholesterol.
The daily recommended cholesterol limit is 300 milligrams of cholesterol and one egg contains about 213.
Choose hot or cold breakfast cereals, such as oatmeal and oat bran, that have about 2 grams of soluble fiber and 4 to 6 grams of total fiber per 1-cup serving.
Researchers at the University of Michigan have identified a new potential therapeutic target for lowering cholesterol that could be an alternative or complementary therapy to statins.
Scientists in the lab of David Ginsburg at the Life Sciences Institute inhibited the action of a gene responsible for transporting a protein that interferes with the ability of the liver to remove cholesterol from the blood in mice. Trapping the destructive protein where it couldn't harm receptors responsible for removing cholesterol preserved the liver cells' capacity to clear plasma cholesterol from the blood, but did not appear to otherwise affect the health of the mice.
In the research, published April 9 in the online journal eLife, scientists found that mice with an inactive SEC24A gene could develop normally. However, their plasma cholesterol levels were reduced by 45 percent because vesicles from liver cells were not able to recruit and transport a critical regulator of blood cholesterol levels called proprotein convertase subtilisin/kexin type 9. PCSK9 is a secretory protein that destroys the liver cells' receptors of low-density lipoprotein- LDL, the so-called "bad cholesterol"-and prevents the cells from removing the LDL.
"Inhibiting SEC24A or PCSK9 may be an alternative to statins, and could work together with statins to produce even greater effects," said Xiao-Wei Chen of the Ginsburg lab, the first author on the paper. "Also, they might be effective on patients who are resistant to or intolerant of statins."
Initial studies of anti-PCSK9 therapies in humans have shown that eliminating PCSK9 can lower cholesterol dramatically and work with statins like Lipitor to lower it even further. The Ginsburg lab's research points to a new area for study: rather than inhibiting PCSK9 itself, perhaps future therapies could block the transport mechanism that allows the destructive protein to reach the LDL receptors.
The paper, "SEC24A deficiency lowers plasma cholesterol through reduced PCSK9 secretion," explains the mechanism by which cells transport PCSK9. Vesicles transport proteins in the cell; the Ginsburg lab's research focused on a specialized type of vesicle packaged by the Coat Protein Complex II, which regulates the metabolism of cholesterol, among many other things. These vesicles selectively transport cargo proteins including PCSK9.
Got high cholesterol? Learn what you can do to lower it quickly - starting today. Read Beyond "Low-Fat"
Even foods that claim to be “low-fat” may contribute significantly to fat intake if you eat more than one serving. The label phrase “low-fat” means the product contains 3 grams or less per serving. Be sure to check the serving size on the nutrition facts label and account for the extra fat (and calories) consumed if you eat more than one serving.
Get Fiber
Research suggests that increasing soluble fiber intake by 5 to 10 grams each day may result in a 5 percent drop in LDL cholesterol. Start the day with a cup of oatmeal, put a ½ cup of beans on your salad at lunch, eat broccoli with dinner and snack on an orange or a pear and you’ll easily meet the target range.
Written and revised by
Gerald Hurowitz, M.D.
Our doctors write and review articles for accuracy and keep them up to date.
health.am provides general information, not medical advice. Always consult a qualified health professional about your own health.
Eggs are no longer on the cholesterol blacklist. The daily recommended cholesterol limit is 300 milligrams of cholesterol and one egg contains about 213. So if you’re going to eat an egg in the morning, simply limit how much cholesterol you get that day from other sources. Substitute some veggies for meat at dinner, or skip the half-and-half in your coffee.
Start The Day Right
Choose hot or cold breakfast cereals, such as oatmeal and oat bran, that have about 2 grams of soluble fiber and 4 to 6 grams of total fiber per 1-cup serving. Add a banana or other fruit to boost fiber even more. This will help keep LDL cholesterol low.
Avoid Double Cholesterol Whammy
Dietary cholesterol can elevate your blood cholesterol levels, but saturated fat has an even worse effect. However, the two are often found in the same foods, including meat, butter and full-fat dairy. So by limiting your intake of foods rich in saturated fat, you’ll also help reduce your intake of cholesterol.
Know Your Sources Of Trans Fat
Since 2006, the FDA has required food manufacturers to list reportable amounts of trans fat on the nutrition facts label. What’s considered reportable? Food manufacturers don’t have to report the trans-fat content if it’s less than 0.5 gram per serving. So check the ingredients list for hydrogenated or partially hydrogenated vegetable oils even if the nutrition facts label reports 0 grams of trans fat.
Go Fish
Twice a week, substitute a fatty fish, such as salmon or tuna, for a higher-fat meat like beef. These fish are rich in omega-3s, a type of polyunsaturated fat, that may help lower your blood cholesterol level when substituted for saturated and trans fats in your diet.
Without those LDL receptors (LDLR), liver cells are not able to remove LDLs from the bloodstream, so protecting the LDLR from PCSK9 would allow the receptors to continue to remove cholesterol.
Walnuts, almonds and other nuts Walnuts, almonds and other nuts can reduce blood cholesterol. Rich in polyunsaturated fatty acids, walnuts also help keep blood vessels healthy.
Eating about a handful (1.5 ounces, or 42.5 grams) a day of most nuts, such as almonds, hazelnuts, peanuts, pecans, some pine nuts, pistachio nuts and walnuts, may reduce your risk of heart disease. Just make sure the nuts you eat aren't salted or coated with sugar.
All nuts are high in calories, so a handful will do. To avoid eating too many nuts and gaining weight, replace foods high in saturated fat with nuts. For example, instead of using cheese, meat or croutons in your salad, add a handful of walnuts or almonds.
"Without SEC24A, much of the PCSK9 couldn't make its way out of the cells to destroy the LDLR, which then clears cholesterol from the blood," Chen said.
The part of the vesicle that selects which proteins to transport is SEC24. By blocking SEC24A gene, the researchers disabled the vesicle's selection of PCSK9. The destructive protein remained trapped within the cells, leaving the LDLR intact and enabling the liver to clear the body of cholesterol that otherwise could accumulate in arteries.
{pagebreak}
"We have no reason at this point to expect that this strategy will be any better than anti-PCSK9 therapy for treating high cholesterol, but it would be another alternative approach, and it's hard to predict which drugs will work the best and be the safest until we actually try them out in people," Ginsburg said.
Ginsburg is a research professor at the Life Sciences Institute, where his laboratory is located. He is also the James V. Neel Distinguished University Professor and the Warner-Lambert/Parke-Davis Professor in the Division of Molecular Medicine and Genetics, Department of Internal Medicine and departments of Human Genetics and Pediatrics at the U-M Medical School and a Howard Hughes Medical Institute Investigator.
Other authors on the paper were Jiandie Lin, Zhuo-Xian Meng, He Wang and Genggeng Yu from the Life Sciences Institute, Yongsheng Bai and Maureen A Sartor from the Department of Bioinformatics and Elizabeth Adams and Andrea Baines from the Program in Cell and Molecular Biology at U-M; Kanika Bajaj and Pengcheng Zhang from the Department of Molecular and Cell Biology, University of California, Berkeley; Zhengping Yi and Danjun Ma from the Department of Pharmaceutical Sciences , College of Pharmacy and Health Sciences, Wayne State University; Hui-Hui Liu and Bin Zhang from the Department of Molecular Medicine, Cleveland Clinic; Stephen G Young from the Department of Medicine and Human Genetics, University of California, Los Angeles; and Randy Schekman from the Department of Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, Berkeley.
1. Set a target.
You know you've got to get your cholesterol number down, but how low do you need to go? That depends on several factors, including your personal and family history of heart disease, as well as whether you have cardiovascular risk factors, such as obesity, high blood pressure, diabetes, and smoking.
If your risk is deemed high, "most doctors will treat for a target LDL of less than 70," says James Beckerman, MD, a cardiologist in private practice in Portland, Oregon. If your risk is moderate, a target LDL of under 130 is generally OK, Beckerman says. If your risk is low, less than 160 is a reasonable target. "The trend now is to treat people earlier, especially if they have two or more risk factors," he says.
2. Consider medication.
Lifestyle modifications make sense for anyone with elevated cholesterol. But if your cardiovascular risk is high, you may also need to take a cholesterol-lowering drug. Michael Richman, MD, medical director of the Center for Cholesterol Management in Los Angeles, calls drug therapy "the only thing that will work fast" to lower high cholesterol. "Everyone should do the basics, like stopping smoking and losing weight," Richman tells WebMD. "But these things lower the risk only modestly. They're nothing to write home about."
Beckerman agrees. "Lifestyle modifications are important, but we should also be emphasizing the benefits of medication when appropriate," he says.
Several types of cholesterol-lowering medication are available, including niacin, bile acid resins, and fibrates. But statins are the treatment of choice for most individuals. "Statins can lower LDL cholesterol by 20% to 50%" says Pamela Peeke, MD, assistant professor of medicine at the University of Maryland School of Medicine in Baltimore.
3. Get moving.
In addition to lowering LDL "bad" cholesterol, regular physical activity can raise HDL "good" cholesterol by up to 10%. The benefits come even with moderate exercise, such as brisk walking.
Robert Harrington, MD, professor of medicine at Duke University School of Medicine in Durham, N.C., urges his patients to go for a 45-minute walk after supper.
Peeke tells WebMD, "I ask people to get a pedometer and aim for 10,000 steps a day. If you work at a desk, get up and walk around for five minutes every hour."
Whatever form your exercise takes, the key is to do it with regularity. "Some experts recommend seven days a week, although I think five days is more realistic," Richman says.
4. Avoid saturated fat.
Doctors used to think that the key to lowering high cholesterol was to cut back on eggs and other cholesterol-rich foods. But now it's clear that dietary cholesterol isn't the main culprit. "Eggs don't do all that much [to raise cholesterol]," Beckerman says. "You don't want to be throwing down six eggs a day, but recent data suggest that it's really saturated fat" that causes increases in cholesterol. And if you cooked your eggs in a slab of butter, don't overlook the fat in the butter.
"One of the first things to do when you're trying to lower your cholesterol level is to take saturated fat down a few notches," says Elaine Magee, MPH, RD, the author of several nutrition books, including the forthcoming Tell Me What to Eat If I Have Heart Disease. "The second thing to do is to start eating more 'smart' fats," Magee says. She recommends substituting canola oil or olive oil for vegetable oil, butter, stick margarine, lard, or shortening while cutting back on meat and eating more fish.
5. Eat more fiber.
Fruits and vegetables, including whole grains, are good sources not only of heart-healthy antioxidants but also cholesterol-lowering dietary fiber. Soluble fiber, in particular, can help lower cholesterol. Beckerman says it "acts like a sponge to absorb cholesterol" in the digestive tract. Good sources of soluble fiber include dried beans, oats, and barley, as well as fiber products containing psyllium.
6. Go fish.
Fish and fish oil are chockablock with cholesterol-lowering omega-3 fatty acids. "Fish oil supplements can have a profound effect on cholesterol and triglycerides," Beckerman says. "There's a lot of scientific evidence to support their use." Fish oil is considered to be quite safe, but check with your doctor first if you are taking an anti-clotting medication.
Magee recommends eating fish two or three times a week. "Salmon is great, as it has lots of omega-3s," she says. But even canned tuna has omega-3s, and it's more consumer-friendly. The American Heart Association also recommends fish as the preferable source of omega-3s, but fish oil capsule supplements can be considered after consultation with your physician. Plant sources of omega-3s include soybeans, canola, flaxseeds, walnuts, and their oils, but they don't provide the same omega-3s as fish. The biggest heart benefits have been linked to omega-3s found in fish.
7. Drink up.
Moderate consumption of alcohol can raise levels of HDL "good" cholesterol by as much as 10%. Doctors say up to one drink a day makes sense for women, up to two a day for men. But given the risks of excessive drinking, the American Heart Association cautions against increasing your alcohol intake or starting to drink if you don't already.
8. Drink green.
Magee suggests green tea as a healthier alternative to sodas and sugary beverages. Indeed, research in both animals and humans has shown that green tea contains compounds that can help lower LDL cholesterol. In a small study conducted in Brazil, people who took capsules containing a green tea extract were able to reduce their total cholesterol.
9. Eat nuts.
Extensive research has demonstrated that regular consumption of nuts can bring modest reductions in cholesterol. Walnuts and almonds seem particularly beneficial. But nuts are high in calories, so limit yourself to a handful a day, experts say.
10. Switch spreads.
Recent years have seen the introduction of margarine-like spreads and other foods fortified with cholesterol-lowering plant compounds known as stanols.
11. Don't smoke.
Smoking lowers levels of HDL "good" cholesterol and is a major risk factor for heart disease.
Funding for the research was providing by the Howard Hughes Medical Institute, the National Institutes of Health and the American Heart Association. The online journal eLife was launched jointly in December 2012 by the Howard Hughes Medical Institute, the Max-Plank Society and the Wellcome Trust. Ginsburg is a member of the Board of Reviewing Editors.
News
News
