Diabetes drug metformin has anti-ageing effects and extends the life of male mice, a new research suggests.
Scientists believe metformin may mimic the effects of extreme calorie restriction.
This regime, which is based on eating a very low calorie diet, is thought to promote healthy ageing.
The human implications of the study are unclear, the researchers report in the journal, Nature Communications.
Rafael de Cabo, of the National Institute on Ageing in Baltimore, Maryland, said calorie restriction in laboratory animals had been shown to increase their lifespan.
His team is searching for interventions – such as a drug – that can mimic these effects.
Diabetes drug metformin has anti-ageing effects and extends the life of male mice
Metformin is one of the most widely prescribed treatments for type-2 diabetes, which occurs mainly in people above the age of 40. It is also used to treat metabolic syndrome, a combination of diabetes, high blood pressure and obesity.
Previous work has shown that metformin can extend the lifespan of simple organisms such as worms, but studies in flies and mammals have given conflicting evidence.
The scientists gave one of two different doses of metformin to middle-aged male mice and found that lower doses increased lifespan by about 5%, and also delayed the onset of age-associated diseases. But they said the higher dose of metformin was toxic and reduced the lifespan of mice.
Further studies were needed to determine if metformin has any effect on human health and lifespan, said Dr. Rafael de Cabo.
“These are very promising results that need to be translated to humans via clinical studies,” he said.
He said the best current advice was to eat a good diet and exercise.
“Right now the best that we can say is probably what your grandmother told you,” Dr. Rafael de Cabo.
“Eat a good diet and exercise are the only two things that we know for sure that they work very well in humans.”
Gorging yourself on as many burgers, chips and cakes as you like one day then eating fewer calories than you find in a cheese sandwich the next might sound like a worrying eating disorder.
However, this regime of chomping away to your heart’s content one day, and virtually starving yourself the next is the latest diet craze. It’s known as “intermittent fasting” or “alternate-day dieting”, and devotees insist the pounds just drop off.
The diet soared in popularity after featuring in a BBC2 Horizon documentary a few weeks ago by health journalist Dr. Michael Mosley. After a month eating normally five days a week and eating just 600 calories the other two days – known as the 5/2 diet – Dr. Michael Mosley lost nearly a stone, reduced his body fat by about 25% and improved his blood sugar and cholesterol levels.
Scientific data seems to show that as well as helping to shift pounds, this alternate-day dieting can help us live longer and reduce the risk of diseases such as cancer, diabetes and even Alzheimer’s.
Now a book on the subject, The Alternate Day Diet, is on Amazon’s list of best-selling diet books, while on internet forums, fans of the plan are swapping tips for the best low-calorie meals for fast days.
However, the regime has drawn criticism from nutritionists who believe that any weight loss on the diet would not be sustainable – and claim that it could even trigger eating disorders.
“The idea that you have a very restricted diet on your <<fast>> days and can eat whatever you like on your <<feed>> days isn’t something I’m very comfortable with,” says Zoe Harcombe, author of The Obesity Epidemic book.
“I did this during my late teens and early 20s. It was called bulimia. My biggest concern is that it’s an approach that could encourage disordered eating in people who are prone to that sort of behavior.”
While every dieter will be used to hunger pangs, the side-effects of such extreme calorie restriction can be even more unpleasant.
“The body does its best to get us to eat,” says Zoe Harcombe.
“So if you’re only eating a quarter of the calories you need, you can expect to experience symptoms associated with low blood sugar. Anything from feeling light-headed and having shaky hands to feeling irritable and lacking concentration.”
Scientific data seems to show that as well as helping to shift pounds, alternate-day dieting can help us live longer and reduce the risk of diseases such as cancer, diabetes and even Alzheimer’s
The diet can also cause digestive problems. Followers are encouraged to up their water consumption on low calorie days.
If they don’t, they can find themselves constipated, with all the associated stomach cramps and bloating. Despite such concerns, many swear by the plan.
While the idea that you can eat anything on your free days sounds great – especially for dieters who struggle to stick to low-calorie eating plans long-term without falling off the wagon – many nutritionists believe that those on the alternate day diet could end up over-indulging on “feast” days, and actually put on weight.
However, Dr. Krista Varady of the University of Illinois in Chicago, one of the scientists involved in research into intermittent fasting, insists that this doesn’t happen.
“Our studies show that people end up losing weight because they can’t fully make up for the lack of food on the fast day on the feed day. And people in our studies didn’t binge. They only ate about 100% to 110% of their calorie needs.”
Opinion is divided on just exactly what a fast entails – some say you should eat nothing at all for anything from 17 to 24 hours, while others argue that you can have 500 calories, but they should all be consumed in a single midday meal.
Dr. Michael Mosley on the Horizon programme ate his 500 calories split over two meals, breakfast (ham and eggs) and dinner (steamed fish and vegetables), as he found that was the best way to avoid feeling hungry or deprived.
Nutritionists do agree that it is vital to eat nutrient-rich foods if you only eat 500 calories a day.
A brunch of kedgeree made from 100 g of smoked haddock, 50 g of wholegrain brown rice and a spring onion, and then a dinner of 100 g of grilled fillet steak with 100 g of steamed broccoli would give you a balanced diet and fall within the calorie restrictions.
It remains to be seen whether this is a long-term solution for those with weight problems, or is just another short-lived diet craze that will go the way of the Grapefruit Diet, the Cabbage Soup Diet, and other extreme plans women have subjected themselves to over the years.
HOW ALTERNATE DAY DIET CAN WORK
Anything you like
Breakfast: 2 eggs scrambled and a slice of ham (250 calories)
Dinner: 100 g (uncooked weight) skinless chicken breast, grilled, served with 150 g new potatoes, boiled, and 100g broccoli, steamed (259 calories)
Anything you like
Breakfast: Kedgeree made from 100g cooked smoked haddock, 50 g (uncooked weight) of wholegrain brown rice, boiled, and a spring onion (265 calories)
Dinner: 100 g fillet steak, grilled, served with 100 g wild rocket and 100 g carrots, boiled (242 calories)
Anything you like
Anything you like
Anything you like
Fasting two days a week could prevent your brain shrinking with age, suggests new research.
Fasting was a common medical treatment in the past, but now new research suggests there may be good reason for it to make a comeback. This is because it seems to trigger all sorts of healthy hormonal and metabolic changes.
Researchers have long known that cutting back animals’ calories over an extended period can make them live up to 50% longer – it’s been harder to prove benefits in humans because few people can stick to this restrictive regimen.
But there’s now emerging evidence to show occasional fasting – which is much more manageable – also carries benefits. Fasting days involve eating between 500 and 800 calories (the usual daily intake for a woman is 2,000 calories, for a man, 2,500).
This intake appears to cause a drop in levels of growth-factor, a hormone linked with cancer and diabetes, as well as a reduction in “bad” LDL cholesterol and triglycerides (fats) in the blood.
Meanwhile, free radicals – the damaging molecules linked to disease – are dampened down. Studies also suggest that levels of inflammation can fall. And now there is the suggestion that fasting protects the brain, too.
“Suddenly dropping your food intake dramatically – cutting it by at least half for a day or so – triggers protective processes in the brain,” explains Professor Mark Mattson, head of neuroscience at the U.S. National Institute On Ageing.
“It is similar to the beneficial effect you get from exercise.”
This could help protect the brain against degenerative diseases such as Alzheimer’s and Parkinson’s.
Prof. Mark Mattson is one of the pioneers of research into fasting – a few years ago he made a breakthrough when he found rats could get nearly all the benefits of calorie restriction if the scientists only cut back their calories every other day. On the next day the rats could eat as much as they liked and yet they showed the same benefits as rats on a low-calorie regimen all the time.
Suddenly it looked as if humans could benefit from a form of calorie restriction regimen that, unlike daily restriction, is feasible to follow. Now results of other trials are revealing the benefits.
In one study, reported last year in the International Journal of Obesity, a group of obese and overweight women was put on a diet of 1,500 calories a day while another group was put on a very low 500-calorie diet for two days, then 2,000 calories a day for the rest of the week.
Both groups were eating a healthy Mediterranean-style diet.
“We found that both lost about the same amount of weight and both saw a similar drop in biomarkers that increase your risk of cancer,” says Dr. Michelle Harvie, a dietitian at Manchester University who led the research.
“The aim was to find which was the most effective and we found that the women in the fasting group actually had a bigger improvement in sensitivity to insulin.” Improved insulin sensitivity means better control of blood sugar levels.
Fasting two days a week could prevent your brain shrinking with age, suggests new research
Last year researchers at Newcastle University reported that they had reversed diabetes in a small number of overweight people by putting them on an 800-calorie diet for eight weeks.
It’s possible that eating small amounts of calories every other day, as Dr. Michelle Harvie’s study allowed, is not only more bearable, but may be particularly effective at getting diabetics’ blood sugar under control.
Now, Prof. Mark Mattson has been investigating the benefits of various fasting regimens on the health of our brain cells.
According to an article that will be appearing in the leading science journal Nature Neuroscience next month, calorie restriction can protect the cells from damage and make them more resistant to stress.
“Part of this effect is due to what cutting calories does to appetite hormones such as ghrelin and leptin,” Prof. Mark Mattson explains.
“When you are not overweight, these hormones encourage growth of new brain cells, especially in the hippocampus.”
This is the area of the brain which is involved in laying down memories. If you start putting on weight, levels of ghrelin drop and brain cell replacement slows.
“The effect is particularly damaging in your 40’s and 50’s, for reasons that aren’t clear yet,” he says.
“Obesity at that age is a marker for cognitive problems later.”
The good news is that this brain-cell damage can be reversed by the two-day fasting regime, although so far Prof. Mark Mattson has shown this only in rats. A human trial is starting soon. There is reason to think it should work. Fasting every other day had a striking effect on people with asthma in a small study he ran a few years ago.
“After eight weeks they had lost eight per cent of their body weight, but they also benefited from the ability of calorie restriction to reduce inflammation. Tests showed that levels of inflammation markers had dropped by 90%.”
“As levels came down, their breathing became much easier,” says Prof. Mark Mattson.
However, Prof. MarK Mattson cautions that patients have to stick to the diet, as symptoms began to return two weeks after giving it up.
Not everyone will find fasting intermittently is something they can manage.
In Dr. Michelle Harvie’s recent study of overweight women, more patients in the continuous dieting group (who had to stick to 1,500 calories a day) wanted to continue with it than those on the two-day fasting regimen.
“It’s going to suit some people more than others,” Dr. Michelle Harvie says.
“For some, being able to cut out 3,000-4,000 calories in two days and then eat normally for the rest of the time is much more attractive than cutting back a little every day; for others it’s too drastic. It gives us another option. My experience is men seem to adapt better to it than women.”
But Prof. Mark Mattson believes these new fasting regimes could help tackle our failure to live more healthily.
“This research shows that successful brain ageing is possible for most individuals if they maintain healthy diets and lifestyles throughout their adult life,” he says.
The trouble is that our diets are too high in calories and we don’t do enough exercise, which is why, he says, brain diseases such as Alzheimer’s are on the rise.
So is there any harm in trying a little intermittent fasting ourselves? As a result of his research, Prof. Mark Mattson now keeps his own calorie intake down.
“I aim for about 1,800 calories a day, nothing drastic,” he says.
“During the week I don’t have any breakfast or lunch but I have a good evening meal. I know it’s not what most dietitians would recommend but it works very well for me.”
Scientists from the University of Southern California say fasting for short periods may help to combat cancer and boost the effectiveness of treatments.
Their study found fasting slowed the growth and spread of tumors and cured some cancers when it was combined with chemotherapy.
It is hoped that the discovery will prompt the development of more effective treatment plans and further research is now under way.
The study, published in the journal Science Translational Medicine, found that tumor cells responded differently to the stress of fasting compared to normal cells.
Instead of entering a dormant state similar to hibernation, the cells kept growing and dividing, in the end destroying themselves.
Lead researcher Professor Valter Longo, from the University of Southern California said: “The cell is, in fact, committing cellular suicide.
“What we’re seeing is that the cancer cell tries to compensate for the lack of all these things missing in the blood after fasting. It may be trying to replace them, but it can’t.”
Prof. Valter Longo and his team looked at the impact fasting had on breast, urinary tract and ovarian cancers in mice.
Fasting without chemotherapy was shown to slow the growth of breast cancer, melanoma skin cancer, glioma brain cancer and neuroblastoma – a cancer that forms in the nerve tissue.
In every case, combining fasting with chemotherapy made the cancer treatment more effective.
Multiple cycles of fasting combined with chemotherapy cured 20% of those with a highly aggressive form of cancer while 40% with a limited spread of the same cancer were cured.
None of the mice survived if they were treated with chemotherapy alone.
Researchers are already investigating the effects of fasting on human patients, but only a clinical trial lasting several years will confirm if human cancer patients really can benefit from calorie restriction.
However, they highlight that fasting could be dangerous for patients who have already lost a lot of weight or are affected by other risk factors, such as diabetes.
Results of a preliminary clinical trial will be presented at an annual meeting of the American Society of Cancer Oncologists (ASCO) in Chicago this June.
Prof. Valter Longo points out that the study only tests if patients could tolerate short fasts of two days before and one day after chemotherapy.
“We don’t know whether in humans it’s effective,” he said.
“It should be off-limits to patients, but a patient should be able to go to their oncologist and say, <<what about fasting with chemotherapy?>> or without if chemotherapy was not recommended or considered.”
Previous research led by Prof. Valter Longo showed that fasting protected normal cells from the effects of chemotherapy but it did not look at cancer cells.
It is now though fasting may be one way to make tumor cells weaker and more vulnerable.
Prof. Valter Longo added: “A way to beat cancer cells may not be to try to find drugs that kill them specifically but to confuse them by generating extreme environments, such as fasting, that only normal cells can quickly respond to.”