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Unique Probiotic Targets Cardiovascular Disease

October 2014

By Celine Thompson

Unique Probiotic Targets Cardiovascular Disease  

In a new and innovative field of medical study, scientists are exploring how probiotics play a much larger and more vital role in our health than we ever could have imagined.

In some impressive research, scientists have determined that specific strains of probiotics have the ability to target disease-specific risk factors—especially those related to cardiovascular disease.1-4

Probiotics have become increasingly popular for their ability to assist in digestion and boost the body’s immunity. But a specific strain of Lactobacillus called L. reuteri 30242 has been found to work in two distinct ways to lower cholesterol: It removes excess cholesterol from the body and increases the metabolism of cholesterol.5,6

Clinical studies show that L. reuteri reduces total and LDL cholesterol levels, without statin drug side effects.5-9

Pharmacological researchers are eager to produce drug versions of these targeted probiotics aimed at lowering cholesterol.10 The good news is that one can initiate supplementation with L. reuteri today and accomplish similar results with this natural strain of a common and beneficial member of the intestinal microbiome.

The Emerging Role Of Gut Microbes In Cardiovascular Health

Researchers are discovering that an important strategy to significantly modify the risk of dying from cardiovascular disease lies within our own intestinal tracts. The human GI tract is home to more than 100 trillion bacteria per person. Together this giant population, which outnumbers human cells by a factor of 10, is referred to as “gut microbiota” or “gut microbiome.”11

The trillions of bacteria in the intestinal tract are a key interface between the body, its genetic structure (or genome), and the environment. The results of these interactions contribute to numerous components that partly determine one’s ultimate cardiovascular risk, including body weight, energy metabolism, and lipid levels.12,13

A 2014 review from the Mayo Clinic observed that, “It will soon be important for practicing clinicians to have an understanding of the basic concepts of the human microbiome and its relation to human health and disease.”14 At Life Extension®, we believe “soon” isn’t soon enough. Now is the time for doctors to take the importance of the gut microbiome seriously—especially as we discover its critical link to cardiovascular disease.

The Genesis Of Targeted Probiotics

The Genesis Of Targeted Probiotics  

Growing knowledge about bacterial biochemistry, as well as about disease-specific risk factors, has made the field of probiotics one of the most exciting research fields in disease prevention and longevity. Long overlooked as a matter of importance, the gut microbiome is now seen as a playing a key role in maintaining optimal health and warding off the diseases of aging.

Probiotics are increasingly being investigated for their ability to change not only risk factors in the gastrointestinal tract, but also those in the body as a whole, especially the cardiovascular system.3,4

At this point, scientists have only just scratched the surface of the potential benefits of probiotics for specific diseases. This is mainly because, in most instances, the mechanisms by which probiotics exert their impressive beneficial effects are still being investigated as is how to customize them to reduce specific disease risk factors.12

Scientists have proposed that L. reuteri has the ability to reduce cholesterol levels in two ways: by increasing cholesterol loss from the body in stool and by increasing the breakdown of cholesterol (catabolism) in the liver.1,15

Preclinical Evidence: L. Reuteri Provides Multiple Cardiovascular Benefits

Elevated blood cholesterol levels, particularly levels of LDL (“bad”) cholesterol, have been associated with cardiovascular disease and early death for several decades. Yet even with so many people taking cholesterol-lowering drugs, some at-risk people are unable to get their cholesterol under control.6

That’s where probiotic cardiovascular protective therapy with L. reuteri comes in.

Animal studies show that L. reuteri has powerful cholesterol-lowering properties. In one study, pigs were fed a high-fat, high-cholesterol, low-fiber diet (like that of many Americans). After four weeks of supplementation with L. reuteri, they experienced significantly lower total and LDL cholesterol compared to control pigs, with no changes in HDL (“good”) cholesterol levels.16

A similar study in mice demonstrated beneficial changes in cholesterol in much less time. After just seven days, mice supplemented with L. reuteri experienced a 38% reduction in total cholesterol, bringing their levels close to those of healthy controls.17 Supplementation also reduced blood triglycerides by 40% and raised the ratio of beneficial HDL to LDL cholesterol by 20%.

The researchers took the study a step further to determine if supplementation with L. reuteri could prevent unhealthy rises in cholesterol. Remarkably, they found that it can. When mice were supplemented with L. reuteri prior to being fed a high-fat diet, the probiotic was able to prevent elevations in cholesterol and increase the beneficial HDL to LDL ratio.18

In addition, L. reuteri-supplemented mice fed a Western-style diet that contained substantial cholesterol gained significantly less body weight, with lower total and liver fat accumulations, than did unsupplemented control mice fed the same diet.19

What You Need To Know
Probiotic Targets Heart Disease

Probiotic Targets Heart Disease

  • Cardiovascular disease continues to be a leading killer of Americans, despite advances in drug and surgical therapies.
  • Probiotics (cultures of beneficial organisms) have long been used to promote gastrointestinal health.
  • New research is producing a generation of “condition-specific” probiotics, each aimed at addressing a particular disease associated with aging.
  • One of the first such probiotic supplements to reach the market is the patent-protected Lactobacillus strain called L. reuteri 30242.
  • L. reuteri produces a specific enzyme that “traps” cholesterol in the intestine and prevents it from being reabsorbed, thereby lowering plasma cholesterol levels.
  • Further cholesterol reductions come from the organism’s ability to increase cholesterol metabolism, thereby promoting its breakdown and excretion.
  • Clinical studies show that L. reuteri supplementation rivals certain cholesterol-lowering drugs in its ability to reduce dangerous total and “bad” cholesterol levels without side effects, while also reducing markers of inflammation that further promote cardiovascular disease.
  • Anyone who is seriously concerned about reducing the risk of early death from heart attack, stroke, or other cardiovascular catastrophe should begin supplementation with this cutting-edge probiotic.

Clinical Evidence: L. Reuteri Substantially Lowers Cardiovascular Risk

Human studies on L. reuteri supplementation have yielded some impressive results.5-7

In one study of adults with elevated cholesterol, subjects consumed either a regular yogurt or one supplemented with L. reuteri.5 Over a six-week period, supplemented patients’ total cholesterol dropped nearly 5% and LDL cholesterol fell by nearly 9%. Supplemented patients also had a significant decline in concentrations of apolipoprotein B-100 (apoB-100), a marker of LDL particle number and a known risk factor for cardiovascular disease.20

Another study demonstrated similarly impressive results in a group of adults with high cholesterol. After taking L. reuteri organisms in capsule form for nine weeks, LDL cholesterol fell by nearly 12%, total cholesterol fell by 9%, non-HDL cholesterol fell by 11%, and apoB-100 fell by 8%, with a reduction in the LDL to HDL cholesterol ratio of 13%.6

This study also demonstrated the long-term benefits of such cholesterol reduction because of its positive impact on two important markers of inflammation: high-sensitivity C-reactive protein (hs-CRP) and fibrinogen. In the patients taking L. reuteri, hs-CRP was reduced by 1.05 mg/L (62%) and fibrinogen was reduced by 14%.

For subjects who began the study with hs-CRP levels in the average or high-risk categories at baseline, 27.1% of supplemented patients reduced their risk category by one or more risk categories (e.g., from high to average risk, from average to low risk, or from high to low risk), compared to only 1.7% of control subjects. And 22% of supplemented patients decreased their hs-CRP risk category by one risk group (e.g., high to average risk or average to low risk), compared to just 2% of controls.6

The Gut Microbiome
The Gut Microbiome

The human GI tract is home to more than 100 trillion bacteria per person. Together this giant population is referred to as the gut microbiota, or gut microbiome.11

These organisms have evolved along with their human hosts to produce a mutually beneficial relationship.11,41 Gut organisms produce critical molecules that humans cannot make for themselves, while humans provide a safe and nutrient-rich environment in return.11

All microbiota come from our mothers (at birth) and from early childhood environments, and this community of organisms can remain remarkably stable throughout our adult lives. Disruptions to the natural bacterial community, however, are not uncommon, and can cause at least temporary changes in the makeup of the community.11

Prolonged, or repeated disturbances, such as frequent antibiotic use or a poor diet, can produce more lasting changes, many of which are harmful to the body as a whole.11 Certain disruptions in the structure of the microbial community have now been associated with specific health problems both within the bowel (e.g., inflammatory bowel disease) and in the body as a whole. This can be seen most clearly in obesity, metabolic syndrome, diabetes, and cardiovascular disease.11,14,42

How L. Reuteri Reduces Cholesterol Levels

The key to success for L. reuteri is in its ability to produce an enzyme called bile salt hydrolase. This enzyme makes cholesterol less absorbable so that instead of being absorbed into the bloodstream, it becomes trapped in the gut, then later excreted in fecal matter.21

Like all fats, cholesterol in its free state cannot dissolve in water (think of how oil and water separate in a jar) and is not easily absorbed on its own. This creates a problem because cholesterol—both LDL and HDL—is beneficial for the body and is necessary for functions such as forming cell membranes and creating hormones.

In order to make cholesterol more absorbable, liver cells produce free bile acids, which are then bonded (conjugated) to the amino acids glycine and taurine and secreted into the intestines.22 Conjugated bile acids are more water-soluble than free bile acids, meaning they are better able to assist with the absorption of cholesterol.15

The problem is that when too much cholesterol is available, either from excess dietary consumption or excess release from the liver into the small intestine, the reabsorption of cholesterol causes the body to maintain blood cholesterol levels higher than necessary, raising cardiovascular disease risk.23-27

The bile salt hydrolase (enzyme) activity of L. reuteri breaks the chemical bonds of conjugated bile acids, thereby releasing free bile acids, which are less water-soluble.15,21,28 In essence, in the presence of L. reuteri, cholesterol molecules may become trapped inside the gut, where they are then excreted.21 This process interrupts regular cholesterol reabsorption, helping lower blood cholesterol levels.

Other Lactobacillus Research

In their search for effective, targeted probiotics that can address the underlying cause of disease, scientists began looking at Lactobacillus, a large genus of beneficial organisms abundant in the human gastrointestinal and female reproductive tracts. In various experiments, Lactobacillus has been bred into numerous strains, each with different biochemical activities. Here are the results of several experiments in which Lactobacillus modified the various risk factors of cardiovascular disease:

  • Probiotic Lactobacillus species fed to obese mice on high-fat diets reduced pro-inflammatory status of blood vessels, while reducing insulin resistance and blood sugar, two major risk factors for heart disease.62
  • Milk fermented with Lactobacillus species lowered glucose, homocysteine, and inflammatory markers in women with metabolic syndrome, a major cardiovascular risk factor.63
  • Critically ill ICU patients at risk of cardiac injury who were given probiotics produced significant decreases in triglycerides and C-reactive protein (CRP, a measure of inflammation) and increases in HDL. No changes were noted in placebo recipients.64

Unique Cholesterol-Lowering Mechanism Of L. Reuteri

L. reuteri is believed to have a second mechanism that further lowers blood cholesterol and cardiovascular risk.

In addition to being reservoirs for excess cholesterol, bile acids are also potent signaling molecules that regulate cholesterol metabolism via the action of the farnesoid X receptor (FXR).29-32 When conjugated bile acids break apart (in the presence of L. reuteri), that signaling is modulated, which then accelerates the breakdown and excretion of cholesterol.22,23 Furthermore, the modified bile acid signaling resulting from L. reuteri limits additional cholesterol absorption from the intestine while boosting cholesterol secretion from the liver back into the intestine for ultimate excretion.24,33,34

In one study, when patients were supplemented with L. reuteri, they showed a significant increase in blood levels of free bile acid and significant decreases in the absorption of plant-derived cholesterol-like molecules.6 In a later re-analysis of data from this study, researchers also found that supplementing with L. reuteri not only improved cardiovascular risk by reducing cholesterol and markers of inflammation, it also improved general intestinal health and reduced symptoms related to diarrhea, compared with placebo recipients.35

Expanding Roles And Mechanisms Of Probiotics’ Widespread Actions4,14
Expanding Roles And Mechanisms Of Probiotics’ Widespread Actions

New Roles For Probiotics To Prevent

Proposed Mechanisms Of Action

Allergic disorders

Autoimmune diseases

Cardiovascular diseases

Clostridium difficile infection

Diabetes

High blood pressure

High cholesterol

High homocysteine levels

Inflammatory bowel disease

Multidrug-resistant organism colonization

Neuropsychiatric illnesses

Obesity and metabolic derangements

Oxidative stress

Modulating central nervous system activity

Modulating immune response

Producing specific molecules

Releasing specific enzymes

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