Chapter 13

Heart Attack: Probiotics and Their Effect on Cholesterol

A MICROSCOPIC VIEW OF THIS CHAPTER

• Cholesterol is a contributing factor to heart disease.
• High serum cholesterol levels contribute to atherosclerosis.
• Atherosclerosis hardens the arteries and leads to heart attacks and strokes.
• Probiotics lower cholesterol levels.
• Bile salt hydrolase in probiotics reduces the cholesterol reabsorption in the gut.
• Bifidobacteria contain bile salt hydrolase as do some Lactobacilli species.
• Probiotics may help your heart by lowering blood pressure.
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Heart disease is the number one killer in Western society. There are many factors that contribute to heart disease including stress, lack of exercise, diet and cholesterol. In fact, there are over 286 risk factors for heart disease. Gender, age and weight are all factors. However, the one that strikes the greatest fear in us is cholesterol. If cholesterol were a Hollywood movie, it would be a blockbuster. The marketing success of health agencies in raising awareness of cholesterol has been enormous.

WHAT IS CHOLESTEROL?

Labeled as a “bad guy,” cholesterol has been thought to play a limited role in the body. Contrary to popular belief, cholesterol has a number of essential functions in the body. In every cell of your body, cholesterol is a major part of the plasma membrane. The plasma membrane surrounds each cell and is involved in transporting nutrients, waste and messages between cells. Cholesterol controls the physical properties of the plasma membrane, which affects the function of membrane proteins such as receptors and transporters. Losing cholesterol in the membrane can cripple many functions of a cell.
Cholesterol has a second important role in the body. It is used to make bile acids which are required for fat digestion in the intestinal tract. The liver uses cholesterol to make bile acids. Cholesterol is also used to make steroid hormones such as estrogen, testosterone, corticosteroids and calciferols. As such, cholesterol is important to the everyday health and functioning of the sexual, mental, immune and skeletal systems in the body.
Eating a low-fat diet will not effectively lower your cholesterol levels. Your liver loves to make cholesterol, perhaps because it plays such a vital role in cell membranes. Thus, even if you do not eat cholesterol, you will have plenty in your body. Also, your body is very effective at absorbing fats. Your intestines are like a sponge for fats. The reason cholesterol levels can rise so easily in your body is that cholesterol is not used as an energy source and therefore does not get broken down as frequently as other fats you eat.
The liver is the major site of cholesterol biosynthesis. Once made, cholesterol is carried from the liver to all parts of the body. Cholesterol is carried around the body by lipoproteins such as high-density lipoprotein (HDL), low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL).
Very low-density lipoprotein (VLDL) is the major lipoprotein made by the liver. VLDL transports cholesterol and triacylglycerol (another fat) from the liver to the other parts of the body. VLDL can change. If the lipids it is carrying are exchanged in a way that the density of the lipoprotein lowers, VLDL can become LDL. Low-density lipoprotein (LDL) has a high concentration of cholesterol. This is why LDL is commonly called “bad cholesterol.”
High-density lipoproteins (HDL) are considered the “good cholesterol” as they collect cholesterol lying around in the arteries of your body and bring it back to the liver to be used in bile production. This is why HDL is commonly called the good cholesterol.

Why Is Cholesterol So Dangerous?

High levels of cholesterol in the blood are associated with an increased risk of developing atherosclerosis, a hardening of the blood vessels that can lead to a heart attack or stroke. In particular, a high level of LDL cholesterol is of concern. Atherosclerosis is the leading cause of death in Western countries; it is more common than all cancers and leukemia combined.

What Factors Increase Your Blood Cholesterol?

Diet, inactivity and genetic factors all contribute to high cholesterol. Consuming foods that are high in cholesterol and fat or eating too many carbohydrates can increase the body’s concentration of cholesterol. Sedentary lifestyles have also been associated with higher cholesterol levels. Cholesterol metabolism is controlled by your DNA. A defect in LDL receptors is known to increase blood cholesterol.

How Does Cholesterol Cause Disease?

It all has to do with the development of an atherosclerotic lesion. A lesion starts with a small tear on the membrane of a blood vessel. This allows plasma to leak into the muscle layers that lie beneath the surface of the blood vessel. The plasma contains cholesterol that triggers inflammation, which in turn causes damage to the tissue. A small, repairable tear in the blood vessel has now turned into a large sore (lesion).
Cholesterol also plays a role in the formation of clots at the site of the lesion. Clots are made by platlets, which are sticky. Cholesterol, calcium and other components of the blood stick to these platlet-covered lesions and can form a clot in the blood vessel. If the clot becomes large enough, it can restrict blood flow. This means not enough blood gets to the tissue downstream, and the tissue suffocates. If the blood vessel with the clot feeds the muscle of the heart, or is in the brain, the result is a heart attack or stroke respectively. But not every lesion will lead to an atherosclerotic plaque. Normally, the cells that line the blood vessles can prevent clotting.
Atherosclerosis
Blood flows through your arteries like water through a hose. Blood vessels (arteries) deliver oxygen and nutrients to organs, muscles and bones. When arteries become clogged with fatty deposits known as plaques, they lose their elasticity and become narrow. This blocks the passage of blood to the body parts that need it. This is known as atherosclerosis. The plaque is sticky and made of fatty substances such as cholesterol. The plaque can collect calcium and waste products. Atherosclerosis is a slow, progressive condition that begins in childhood and can occur anywhere in the body. It most commonly affects large- and medium-sized arteries. There are no symptoms for atherosclerosis and no direct treatment. Lifestyle changes are thought to be the best way to prevent fatty deposits in arteries.

How Can You Prevent or Limit the Development of Atherosclerosis?

By lowering cholesterol levels, you can slow the development of atherosclerotic plaques. One way cholesterol is removed from the blood stream is by cholesterol-requiring cells. Tissues that make steroid hormones commonly require cholesterol. These cells will remove low-density lipoprotein (LDL) from circulation through a process called endocytosis. Cholesterol carried by LDL can only be used by cells with a specific receptor—the LDL receptor. A genetic problem with this receptor is associated with high cholesterol levels and an increased risk of heart attack and stroke.
Another way cholesterol is removed from your blood is by the liver. Excess cholesterol can be transported back to the liver by high-density lipoprotein (HDL). A high level of HDL in the blood is associated with a decreased risk of cardiovascular disease. The liver can either recycle the cholesterol and make new lipoproteins or dispose of it in the bile. Certain foods are associated with an increase in HDL. Fish oil is one such food.
There are other ways to reduce cholesterol in the body, and current therapy usually involves multiple approaches. Here are some of the most commonly used therapies to reduce cholesterol levels in the body.
1. Limit dietary intake of cholesterol. Cholesterol does not occur in plants; therefore, your diet should consist mainly of fresh fruits and vegetables, nuts, grains, beans and seeds.
2. Increase good fat consumption. Polyunsaturated fatty acids found in plants and some animals, e.g., fish, support healthy inflammation in the body and may reduce inflammation associated with lesion development.
3. Increase fiber intake. This will help inhibit the uptake of cholesterol from the intestinal tract. About 95% of cholesterol in bile acids is re-absorbed in the intestinal tract and recycled.
4. Inhibit liver synthesis of cholesterol. This is how the pharmaceutical family of drugs called statins target high cholesterol levels. Red yeast rice is a natural product thought to offer cholesterol-lowering effects much like statins.
5. Limit the amount of cholesterol re-absorbed from the bile in the intestines. Probiotics can help produce enzymes that prevent this reabsorption of cholesterol.

THE PROBIOTIC CONNECTION

Elevated levels of cholesterol in the blood have been linked to an increased risk of heart disease. Results from early studies suggest that the consumption of yogurt, a natural source of probiotics, contributes to a reduced cholesterol level in the blood. A number of studies since have found that use of probiotics can reduce cholesterol levels by as much as 22% to 33%.
How do bacteria in the intestinal tract have anything to do with cholesterol? There are many ways in which probiotics affect cholesterol metabolism in the body. The exact means by which this occurs is not completely understood, but it is likely that probiotics lower cholesterol through a number of ways.
Probiotics may reduce cholesterol levels in the body by simply using or absorbing cholesterol. The bacteria cells themselves may use some cholesterol in the intestines. However, it is a second mechanism that is more likely the cause of the decrease in cholesterol levels seen in populations that use probiotics regularly.
Probiotics can reduce cholesterol levels by as much as 22% to 33%.
First, let’s review the movement of cholesterol from the liver into the bile acids in the intestine and re-absorption by the body. The liver uses cholesterol to make bile acids (cholic and chenodeoxycholic acid), which are sent from the liver through the bile duct into the intestinal tract. A lot of the cholesterol in bile acids are re-absorbed by the body, and the rest are excreted in the feces (about 5%). If less cholesterol is re-absorbed from the intestines, then the liver needs to remove more cholesterol from the blood, which in turn causes a drop in cholesterol levels.
The ability of probiotics to lower cholesterol levels is due to their ability to produce bile salt hydrolase (BSH). Bile salt hydrolase is an enzyme that converts bile into deconjugated bile salts. Deconjugated bile salts cannot be reabsorbed by the body; thus, more bile acid is lost in the feces and less cholesterol is re-absorbed and sent to the liver. Since about 95% of bile salts are normally re-absorbed, this enzyme can have a great effect on cholesterol levels. The production of bile salt hydrolase by probiotics appears to lower cholesterol by reducing the amount of cholesterol absorbed in the gut and increasing the amount of cholesterol pulled from the blood by the liver to make bile.
In recent years, interest has increased in the use of probiotics to lower cholesterol levels. Researchers have screened more than 300 strains of bacteria for bile salt hydrolase activity. Bile salt hydrolase activity was found to be common in almost all Bifidobacterium and some Lactobacillus but not in L. lactis and S. thermophilus. Probiotics are a good addition to the diet of people with high cholesterol.
Some research papers suggest that probiotics lower cholesterol levels by inhibiting the ability of the liver to make cholesterol. Another paper suggested probiotics increase the ability of low-density lipoproteins (LDL) to hold cholesterol. It is not certain which way probiotics lower cholesterol.
There appears to be evidence that probiotics play a role in cholesterol management. Controlled clinical trials have found that probiotics reduced cholesterol in people with hyperlipidemia (high cholesterol). A crossover study of 29 healthy women, ages 19 to 56, found that the long-term daily consumption of 300 g of a plain or probiotic-containing yogurt increased high-density lipoprotein (HDL) cholesterol. The yogurt was enriched with Lactobacillus acidophilus and Bidfidobacterium longum.
A meta-analysis (a review of the existing studies to date) of six studies investigating a probiotic yogurt product containing E. faecium found that the yogurt caused a 4% decrease in total cholesterol and a 5% decrease in low-density lipoprotein (LDL) cholesterol. The connection between probiotics and cholesterol does not only appear to work theoretically but also appears to be supported by clinical research. Watch for more research in this area in the future.
Probiotics may help your heart by doing more than lowering cholesterol. A controlled, randomized, double-blind study involving 36 male smokers who consumed 50,000 CFUs of L. plantarum had a decrease in oxidative stress and inflammation. Thus, L. plantarum appears to effectively reduce some heart disease risk factors.

PROBIOTICS TO REDUCE BLOOD PRESSURE

About 50 to 60 million people in the United States are estimated to have hypertension (elevated blood pressure). This may seem like a big number until you realize that there is a 60% higher rate of hypertension in Europe than in the United States or Canada. Hypertension is a risk factor for heart disease. High blood pressure can cause strokes, heart attacks and heart and kidney failure. It is also related to dementia and sexual problems. Blood pressure is the force on the walls of the arteries as the blood circulates. When it is too high, as in hypertension, the arteries can become damaged and disease can develop.
Probiotics may help fight hypertension. Animal studies have found that Lactobacilli probiotics have a mild effect on blood pressure. This may have to do with the ability of probiotics to produce enzymes that break down proteins involved in blood pressure. There have only been a few studies looking at the effects of probiotics on hypertension, but the results suggest that probiotics may be able to lower systolic blood pressure by 10-20 mm Hg. The consumption of Lactobacilli, or products made from them, such as milk that is fermented by Lactobacilli, may reduce blood pressure in mildly hypertensive people.
Population (epidemiological) studies suggest that milk consumption or dairy proteins are related to a decreased risk of hypertension. Some intervention studies have shown milk products and dairy proteins have a blood pressure-lowering effect. Milk proteins are broken down by enzymes in your stomach and by enzymes produced by Lactobacilli. The broken-down milk proteins are called milk peptides. Several milk peptides have antihypertensive effects in animal and in clinical studies. It is thought that milk peptides inhibit an enzyme that causes blood pressure to rise, called angiotensin-converting enzyme. Milk peptides may also have other mechanisms to lower blood pressure such as binding minerals and preventing blood clotting. As probiotics are involved in the creation of milk peptides, having a healthy population of Lactobacilli in your body may help you keep your blood pressure low. Watch for future studies to test if probiotic supplementation can truly affect blood pressure.
The ways in which probiotics can improve your health have expanded beyond the intestinal tract. Although they seem promising, most of the benefits of probiotics outside of the intestinal tract are based on preliminary science. As for hypertension, the research is only laboratory based and has not been tested in humans.

SUMMARY

Hypercholesterolemia (elevated blood cholesterol levels) is considered a major risk factor for the development of coronary heart disease. Drugs used to treat this condition, e.g., statins or bile acid sequestrants are often expensive and can have unwanted side effects. Yogurt consumption has been found in studies to beneficially affect cholesterol levels. The probiotics in yogurt are thought to cause these cholesterol-lowering health benefits. Probiotic supplementation may play a role in reducing cholesterol according to preliminary research. Many probiotic species found in North American probiotic supplements and dairy products are known to have bile salt hydrolase, which is an enzyme thought to help lower cholesterol. The cholesterol-lowering effects of probiotics are not large, but are beneficial. The ability of probiotics to lower cholesterol is a benefit that can help us all. Probiotics may also play a role in reducing hypertension. More research is needed before probiotics can be used as an effective treatment for high blood pressure.