Sunday, September 02, 2012

Calorie restriction doesn't help in primates

This is a big blow to the conventional wisdom.  The conventional wisdom was however mainly founded on rodent studies and I have always said that generalizing lifespan effects from short-lived creatures, such as rodents, to long-lived creatures, such as humans,  is absurd.  Things that help rodents are probably already embedded in human physiology

To those who enjoy the pleasures of the dining table, the news may come as a relief: drastically cutting back on calories does not seem to lengthen lifespan in primates.

The verdict, from a 25-year study in rhesus monkeys fed 30% less than control animals, represents another setback for the notion that a simple, diet-triggered switch can slow ageing. Instead, the findings, published this week in Nature, suggest that genetics and dietary composition matter more for longevity than a simple calorie count.

“To think that a simple decrease in calories caused such a widespread change, that was remarkable,” says Don Ingram, a gerontologist at Louisiana State University in Baton Rouge, who designed the study almost three decades ago while at the National Institute on Aging (NIA) in Bethesda, Maryland.

When the NIA-funded monkey study began, however, studies of caloric restriction in short-lived animals were hinting at a connection. Experiments had showed that starvation made roundworms live longer. Other studies had showed that rats fed fewer calories than their slow and balding brethren maintained their shiny coats and a youthful vigour. And more recently, molecular studies had suggested that caloric restriction — or compounds that mimicked it — might trigger a cascade of changes in gene expression that had the net effect of slowing ageing.

In 2009, another study, which began in 1989 at the Wisconsin National Primate Research Center (WNPRC) in Madison, concluded that caloric restriction did extend life in rhesus monkeys. The investigators found that 13% of the dieting group died from age-related causes, compared with 37% of the control group.

One reason for that difference could be that the WNPRC monkeys were fed an unhealthy diet, which made the calorie-restricted monkeys seem healthier by comparison simply because they ate less of it. The WNPRC monkeys’ diets contained 28.5% sucrose, compared with 3.9% sucrose at the NIA. Meanwhile, the NIA meals included fish oil and antioxidants, whereas the WNPRC meals did not. Rick Weindruch, a gerontologist at the WNPRC who led the study, admits: “Overall, our diet was probably not as healthy.”

Further, the WNPRC control group probably ate more overall, because their meals were unlimited, whereas NIA monkeys were fed fixed amounts. As adults, control monkeys in the WNPRC study weighed more than their NIA counterparts. Overall, the WNPRC results might have reflected an unhealthy control group rather than a long-lived treatment group. “When we began these studies, the dogma was that a calorie is a calorie,” Ingram says. “I think it’s clear that the types of calories the monkeys ate made a profound difference.”

Researchers studying caloric restriction in mice have become accustomed to mixed results, which they attribute to genetic diversity among strains. Genetics probably explains part of the variation between the monkey studies, too, as the NIA monkeys were descended from lines from India and China, whereas the Wisconsin monkeys were all from India.

The molecular effects of caloric restriction have also turned out to be complicated. Using compounds such as resveratrol, found in red wine, scientists have triggered the stress response that caloric restriction activates, which shuts down non-vital processes in favour of those that ward off disease. But hopes that ageing could be delayed by targeting a single gene or protein in a single molecular pathway have faded, as researchers have learned that the key pathways vary according to the animal.“It may take us a decade to sort out longevity networks,” says David Sinclair, a geneticist at Harvard Medical School in Boston, Massachusetts.

Meanwhile, there is a dearth of evidence that caloric restriction slows ageing in humans. Observational studies have found that people of average weight tend to live longest [by a small margin]. Nir Barzilai, a gerontologist at Albert Einstein College of Medicine in New York, says that the centenarians he studies have led him to believe that genetics is more important than diet and lifestyle. “They’re a chubby bunch,” he says.

A more nuanced picture would suit Ingram, who enjoys an occasional feast of Louisiana crawfish. Ingram says that he looks forward to studies of how diet composition, rather than caloric intake, affects ageing. “Is the human lifespan fixed?” he asks. “I still don’t believe that for a minute.”


Statin fanatic ignores issues of therapeutic compliance (discontinuing treatment)

It seems very easy to find people who have had bad side-effects from statins but clinical trials report very few side-effects.  Why?  Because people enrolled in clinical trials are embarrassed to tell the researchers that they have flushed the garbage down the toilet because they couldn't tolerate it.  "I'd rather risk a heart attack" is one comment I have head

Statins should be given to all over-50s, regardless of their health history, because they dramatically cut the risk of heart attacks and strokes in later life, one of the UK's leading experts has said.

Currently statins are given only to high-risk patients, around eight million people, who have high cholesterol or have a risk of heart disease.

But there is 'clear evidence' that healthy people can also benefit based on their age alone, says Professor Sir Rory Collins.

He led the world's largest study to investigate statins in the prevention of cardiovascular disease which proved that cutting levels of 'bad' LDL cholesterol in the blood saved lives.

The risk of having a major vascular event such as a heart attack is cut by one-fifth for each 1.0mmol/L (millimoles per litre) fall in LDL, whether in high or low risk patients.

But current guidelines on their use - and misguided safety fears about muscle pain and memory loss - are restricting the range of people who can take them, he said.

'At 50 you should be considering it and whether you should be taking them at an earlier age is an open question' he said.

'If you start treatment earlier and continue for longer the benefits will be much greater, you're not trying to unfur the arteries, you're preventing them from furring in the first place' he said.

Prof Collins, who was giving a keynote lecture at the European Cardiology Congress in Munich, said evidence from 130,000 patients taking statins in trials show they are safe.

Yet drug safety watchdogs here and in the US have insisted on flagging up relatively minor side effects which are putting patients off the drugs, he said.

These include memory loss, depression, sexual difficulties and depression, while recent research suggests cataracts and diabetes may be more common in patients taking statins.

Trial data shows only one significant side effect, myopathy or muscle pain, which affects one in 10,000 patients, said Prof Collins.

He said: 'We need to look properly at the safety of statins. The reality is that these drugs are remarkably safe, but the problem is that high risk patients are getting the message that these drugs have side effects.'

Prof Collins, 57, went to his GP a fortnight ago to ask about taking statins despite a relatively low cholesterol level, and was dismayed to learn she could not get high risk patients to take them because of fears about side effects.

Research earlier this year co-ordinated by the Clinical Trial Service Unit Oxford University, where Prof Collins is co-director, reviewed findings from 27 statin trials involving 175,000 people, some of whom were at low risk of heart problems.

The drugs cut the risk of heart attacks, strokes and operations to unblock arteries by one third or more.

The benefits were gained no matter what level of cholesterol patients started out with. Healthier people who were given statins also had lower overall death rates than those who were given a placebo.

It concluded the positives greatly exceeded any side-effects from taking the drugs.

More than eight million adults are already taking statins, but it is estimated that routine use by the over 50s would lead to 10,000 fewer heart attacks and strokes a year, including 2,000 fewer deaths in the UK.

The small cost of the drugs - as low as £16 a year - would be outweighed by NHS savings due to the reduced number of heart attacks and strokes.

At present, statins are restricted to those with at least a 20 per cent risk of having a heart attack or stroke over the next five years.

But, said Prof Collins, trial data shows very low risk groups can benefit where individuals have just a five to 10 per cent chance of heart disease, and even lower.

He said there did not appear to be a threshold at which the drugs didn't work and the longer they were taken, the greater the benefit.

'We need to review the guidelines and the current thresholds should go,' said Prof Collins, who claimed medical tests such as liver function were also unnecessary.

Professor Peter Weissberg, medical director of the British Heart Foundation, said: 'The issue is where do you set the threshold between low, normal and high risk.

'The current arbitrary threshold was decided by cost but now statins are off patent (and much cheaper) it may be appropriate to see if there are benefits for more people - the threshold is a bit too high,' he added.


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