Cholesterol Lowering Drugs – Statins – are Linked to Improved Gut Bacteria Composition in Obese People

The human gut microbiota consists of trillions of bacteria, fungi and virus constituting an inner chemical factory producing a multitude of microbial compounds affecting immunity, neurobiology and metabolism of the human host.

It has for long been known that imbalances in the composition of gut microbes link with a variety of chronic human disorders spanning from obesity, diabetes inflammatory bowel diseases to depression, schizophrenia, autism and Parkinson. In addition, it is known that unhealthy dieting and use of some medications, for instance stomach acid neutralizers, the so-called proton pump inhibitors, are associated with a further disruption of the microbial communities of the gut.

Now, in a new paper in the scientific journal Nature, The MetaCardis investigators explore gut bacteria in almost 900 individuals from Denmark, France and Germany.

The intestinal microbiota in obese individuals had previously been shown to differ from those in lean subjects with a poor bacterial diversity, a relative depletion of health promoting bacteria and the remaining bacteria dominated by an inflammatory tone.

In their Nature article, the researches now define a cluster of bacteria called Bact2 enterotype, which is found in 4% of lean and overweight people but in 18% of obese individuals who did not use statin drugs, a group of cholesterol lowering medications.

However, in other obese study participants who were treated with statins, the prevalence of the unhealthy Bact2 enterotype was significantly lower (6%) than in their non-treated counterparts (18%) – comparable to levels observed in non-obese participants (4%). The same trend was validated in a Flemish study sample of about 2000 participants.

Statins are commonly prescribed to reduce risk of developing cardiovascular diseases like myocardial infarction and stroke. It is estimated that more than 200 million people worldwide are prescribed statins. Besides their cholesterol-lowering effects, statins also tend to appease patients’ systemic inflammation levels which in part may be related to a disrupted gut microbiota.

The results suggest that statins could potentially modulate the disrupted gut microbiota and linked inflammation in obesity. Previous experiments in rodents have shown an impact of statins on bacterial growth, which might benefit non-inflammatory bacteria and underlie the anti-inflammatory effects of statin therapy. Obviously, clinically controlled human trials are needed to address whether statins mediate some of their anti-inflammatory effect via an improvement of the Bact2 enterotype of an aberrant gut microbiota.

Source: University of Copenhagen

Research Suggests Statins Could Lower Ovarian Cancer Risk

A genetic study has found evidence to suggest that women who take statins in the long term could be less likely to develop ovarian cancer, according to new research funded by Cancer Research UK published recently.

The same result was also found in women who carry the BRCA1/2 gene fault. Having the BRCA1/2 fault puts women at a higher risk of ovarian cancer than the general population.

The research published in JAMA studied genes and the extent to which they inhibit the enzyme HMG-CoA reductase – which is responsible for regulating cholesterol in the body – and is the exact enzyme targeted by statin drugs to reduce cholesterol.

While the study suggests that statins could lower ovarian cancer risk, more research needs to be done specifically looking at their use and impact on women’s risk of developing the disease.

The researchers based at the University of Bristol looked at 63,347 women between the ages of 20 and 100 years old, of whom 22,406 had ovarian cancer. They also looked at an additional 31,448 women who carried the BRCA1/2 fault, of whom 3,887 had ovarian cancer. The study used an approach called Mendelian randomization, which involves analysing the genetic data from thousands of people.

Statins may protect against the development of ovarian cancer because they’ve been shown to induce apoptosis – one of the body’s ways of getting rid of old, faulty or infected cells – and to stop tumours from growing in laboratory studies. Another line of thought is that statins lower circulating cholesterol, which helps regulate cell growth, though this research suggests that lower circulating cholesterol was not the method by which statins may reduce ovarian cancer risk.

The findings suggest that long-term statin use could be associated with an estimated 40% reduction in ovarian cancer risk in the general population, although the estimate comes from looking at gene variation rather than statins themselves, and the exact mechanism by which these genes are associated with lower ovarian cancer risk is unclear.

Ovarian cancer is the 6th most common cancer in women in the UK. There are around 7,400 cases each year, and out of those with a known stage at diagnosis, almost 6 in 10 are diagnosed at a late stage. Around 4,100 women die from the disease every year in the UK.

There is no test that reliably picks up ovarian cancer at an early stage, so chemoprevention could be an important approach to saving lives.

Professor Richard Martin, from the University of Bristol, said: “Our findings open up the possibility of repurposing a cheap drug to help prevent ovarian cancer – especially in women who are at a higher risk. It’s incredibly interesting that women whose bodies naturally inhibit the enzyme targeted by statins have a lower risk of ovarian cancer, but we don’t recommend anyone rushes to take statins specifically to reduce ovarian cancer risk because of this study.

“It’s a promising result and I hope it sparks more research and trials into statins to demonstrate conclusively whether or not there’s a benefit.”

Dr Rachel Orritt, Cancer Research UK’s health information manager, said: “This study is a great first step to finding out if statins could play a role in lowering ovarian cancer risk, and justifies future research into this area.

“But there’s not yet enough evidence to know if statins themselves could reduce the risk of developing ovarian cancer safely. And it’s important to remember that the risk of developing ovarian cancer depends on many things including age, genetics and environmental factors. Speak to your doctor first if you have any concerns about your risk.”

Source: EurekAlert!

Cholesterol Drugs Might Help Curb ‘High-Risk’ Prostate Cancers

Drugs that many men with prostate cancer might already be taking — cholesterol-lowering statins — may help extend their survival if they have a “high-risk” form of the disease, new research suggests.

High-risk patients include men with high blood levels of prostate specific antigen (PSA) and a “Gleason score” of 8 or more. Gleason scores are a calculation used to gauge prognosis in prostate cancer. Men with a high Gleason score may develop difficult-to-treat cancers.

Prior research had suggested that statins and the diabetes drug metformin (often prescribed together) have anticancer properties. However, it hasn’t been clear which of the two drugs is the bigger cancer-fighter, or whether either might help against high-risk prostate cancer.

To help answer those questions, a team led by Grace Lu-Yao of the Sidney Kimmel Cancer Center–Jefferson Health, in Philadelphia, tracked data on nearly 13,000 high-risk prostate cancer patients. All were diagnosed between 2007 and 2011.

The study couldn’t prove cause and effect, but it found that statins, taken alone or with metformin, did seem associated with an increase in survival.

Men who took both statins and metformin had higher median survival (3.9 years) than those who took statins alone (3.6 years), metformin alone (3.1 years), or those who did not take either drug (3.1 years).

The study was published in the journal Cancer Medicine.

“Both metformin and statins have been associated with longer life in prostate cancer patients, yet because they are commonly prescribed together, no study we know of has looked at these two medications separately,” Lu-Yao said in a center news release. She’s associate director of population science at the center.

“With respect to prostate mortality, metformin plus statin was associated with a 36% reduction in risk of death followed by statins alone,” Lu-Yao added.

The study also found that those who took one of three types of statin — atorvastatin, pravastatin or rosuvastatin — had longer survival than those who did not take any statins. A similar benefit was not seen with a fourth statin, lovastatin.

Because prostate cancer thrives on testosterone, patients often receive treatments that reduce levels of male hormones (androgens). The new study found that among patients who received such therapies, those who took atorvastatin had a longer median time to prostate cancer progression than those who didn’t take statins.

It’s not clear why such effects were limited to atorvastatin, Lu-Yao said, but it appears to have the best “bioavailability” of the statin drugs and lingers longest in the body.

The research team believes that, based on the existing evidence, a clinical trial should be conducted to assess the effectiveness of statins and the combination of statins/metformin in extending survival of prostate cancer patients.

Two prostate cancer specialists unconnected to the new study agreed that the findings show promise.

“It appears that there may be a place in the treatment of prostate cancer for statins,” said Dr. Elizabeth Kavaler, a urology specialist at Lenox Hill Hospital in New York City. “However, we are not yet at a point where we can use the data to direct patient care.”

She believes testosterone may be key here. According to Kavaler, higher cholesterol levels promote higher levels of androgens, which in turn help encourage the growth of prostate cancer. Statins may help slow that process, Kavaler explained.

Dr. Manish Vira is vice chair for urologic research at The Arthur Smith Institute for Urology in New Hyde Park, N.Y. He agreed that the findings are encouraging, and noted that “a dozen actively recruiting clinical trials using either metformin or a statin in prostate cancer treatment” are already underway.

Source: HealthDay

Statins Won’t Harm Aging Brains, and May Even Help

Steven Reinberg wrote . . . . . . . . .

Concerns that cholesterol-lowering statin drugs can impair brain health appear to be unfounded, according to new research.

“Statins won’t make you stupid or cause memory loss,” said lead researcher Dr. Katherine Samaras, a professor of medicine at St. Vincent’s Clinical School of Medicine in Darlinghurst, Australia.

And for some people at risk of dementia, statins like Lipitor (atorvastatin) and Crestor (rosuvastatin) may improve memory and mental functioning, her team found.

Many millions of people take statins because of heart disease or high cholesterol. But reports that the drugs could cause memory loss led the U.S. Food and Drug Administration in 2012 to require a black box warning on all statin medications, she said.

However, “we could find no overall impact on memory or any other aspect of cognitive function over six years in a large population of older people, who had extensive testing every two years,” Samaras said.

The observational nature of this study means the research can’t be considered conclusive, only that a strong link exists, the researchers noted.

“Any person who takes statins and is concerned about their memory and cognition should discuss this with their doctor. However, overall, we should be greatly reassured by the study findings,” Samaras said.

For the study, she and her colleagues collected data on more than 1,000 people aged 70 to 90 who took part in the Sydney Memory and Aging Study. About 600 took statins and had done so for an average of nine years.

All of the participants had their memory and cognitive skills — such as processing speed and language — tested at the start of the study. No difference was seen between statin users and nonusers, according to the report.

Some people also had MRI scans to assess their brain volume. The MRIs showed no significant difference in brain volume among statin users and nonusers over two years.

And over six years, the researchers found no significant difference between memory and mental ability among those who did and didn’t take the drugs.

Among 99 people who started taking statins during the study, however, Samaras and colleagues found statins were linked to a slower rate of memory loss.

As expected, statins did protect people with heart disease from heart attacks. Within this group, the drug also resulted in a slower rate of a decline in memory, compared with people who didn’t take statins.

Moreover, in people with heart disease, diabetes or other risk factors for dementia, statin use slowed down mental decline in comparison with nonusers who had the same conditions.

Looking at people who had the APOE-4 gene mutation, which puts them at high risk for Alzheimer’s disease, the researchers found statins appeared to significantly slow the rate of mental decline.

However, among participants without heart disease who took statins, the rate of memory decline was similar to those who didn’t take the drug, the findings showed.

The report was published online in the Journal of the American College of Cardiology.

Dr. Costantino Iadecola, a professor of neurology and neuroscience at Weill Cornell Medicine in New York City, co-authored an editorial accompanying the study. He said, “Statins have many effects on the brain.”

The brain is 80% fat and has the most cholesterol of any organ in the body, and is very sensitive to any changes in fat, said Iadecola.

“So it’s not surprising that modulating cholesterol affects the brain,” he said.

Reducing cholesterol in the brain may reduce two changes linked to Alzheimer’s, namely beta-amyloid plaques and tau tangles, he noted.

But whether statins have a positive effect on preserving cognitive function requires more study, Iadecola said.

In the meantime, he doesn’t advise taking statins for the sole purpose of maintaining your mental abilities, since these drugs can have side effects.

Source: HealthDay


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Statins Safe and Likely Effective for Preventing Cardiovascular Events in Patients with Rheumatoid Arthritis

Results from a large clinical trial indicate that patients with rheumatoid arthritis are likely to experience the same level of cardiovascular benefits from statins as other individuals, without additional risks. The findings appear in Arthritis & Rheumatology, an official journal of the American College of Rheumatology.

Patients with rheumatoid arthritis have an approximately 50 percent higher risk of experiencing cardiovascular events such as heart attack and stroke compared with the general population. By lowering LDL cholesterol, statins are known to help prevent cardiovascular events in certain high-risk individuals, but it’s unclear whether they are safe and effective for patients with inflammatory conditions such as rheumatoid arthritis.

To investigate the potential risks and benefits of statins in moderate risk patients with rheumatoid arthritis, researchers designed the Trial of Atorvastatin for the Primary Prevention of Cardiovascular Events in Patients with Rheumatoid Arthritis (TRACE RA), a multi-center, randomized, double-blind trial comparing the statin atorvastatin with placebo.

The trial included 3,002 patients with rheumatoid arthritis who were over aged 50 years or had rheumatoid arthritis for more than 10 years, without clinical atherosclerosis, diabetes, or myopathy. Patients were randomized to receive atorvastatin 40mg daily or placebo.

During a median follow-up of 2.5 years, 1.6 percent of patients who received atorvastatin and 2.4 percent of patients receiving placebo experienced cardiovascular death, heart attack, stroke, transient ischemic attack, or any arterial revascularization. After adjustments, there was a 40 percent lower risk of cardiovascular events for patients taking atorvastatin, although the difference was not statistically significant. This was because the overall rate of events was low.

At the end of the trial, patients taking atorvastatin had significantly lower LDL cholesterol as well as significantly lower levels of C-reactive protein, a marker of inflammation, compared with patients taking placebo. Adverse events in the atorvastatin and placebo groups were similar.

The paper’s lead author is Professor George Kitas of Dudley Group NHS Foundation Trust, while co-senior authors are Professor Jill Belch of the University of Dundee and Professor Deborah Symmons of the University of Manchester.

“The trial found that the statin reduced levels of cholesterol by similar amounts as has been seen in other populations studied. The results also show that it is as safe for patients with rheumatoid arthritis to take statins as for the general population,” said Prof. Symmons. “In addition, because of the low overall rate of cardiovascular events in the trial population, there is no indication for all patients with rheumatoid arthritis to be prescribed a statin. This is unlike diabetes where the great majority of patients are recommended to take a statin.”

The study authors recommend that patients with rheumatoid arthritis be prescribed statins according to national or local guidelines for managing cardiovascular risk in the general population.

Source: Wiley


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