High protein diet not as bad for you as smoking

Reposted, without modification from: http://www.nhs.uk/news/2014/03March/Pages/high-protein-diet-may-be-harmful-for-middle-aged.aspx

crabsallover highlights, key points, comments / links.

For me, the message from this research is that "low protein intake during middle age followed by moderate to high protein consumption in older adults may optimise health and longevity." 

From my other IGF-1 posts they seem to me to indicate to me that low IGF-1 levels are implicated in a long, healthy life. IGF-I (wikipedia).

Interesting comments to the Levine et al paper particularly from Jason Cholewa about high protein and body building.

NHS.uk Choices

“People who eat diets rich in animal protein carry similar cancer risk to those who smoke 20 cigarettes each day,” reports The Daily Telegraph.

We have decades of very good evidence that smoking kills and – fortunately for meat lovers – this latest unhelpful comparison with high protein diets largely appears to be a triumph of PR spin.

The warning was raised in a press release about a large study which found that for people aged 50-65, eating a lot of protein was associated with an increased risk of dying.

However, the study, which assessed the diets of Americans in a single 24-hour period (rather than long-term), found in those aged over 65 that a high protein diet was actually associated with a reduced risk of death from any cause or from cancer. These differing findings meant that overall there was no increase in risk of death, or from dying of cancer with a high protein diet.

How much protein should I eat?
In this study, on average people ate 51% of their calories in the form of carbohydrates, 33% as fat and 16% as protein (11% animal protein). This is likely to be higher in fat and lower in carbohydrates than that recommended on the “Eatwell Plate” which shows the relative proportions of food that we should aim to eat.

There are several reasons to be cautious when interpreting the results of this study, including that the researchers did not take into account important factors such as physical activity in their study.

The claim in much of the media, that a high protein diet in middle-aged people is “as dangerous as smoking” is unsupported. We need to eat protein, we do not need to smoke.

Where did the story come from?

The study was carried out by researchers from the University of Southern California (USC) and other research centres in the US and Italy. It was funded by US National Institutes of Health, National Institute on Aging, and the USC Norris Cancer Center. The study was published in the peer-reviewed journal Cell Metabolism and has been made available on an open access basis to read for free.

In general, reporting of the results of the study was reasonable. However, the prominence given to the story (which featured as a front page lead in The Daily Telegraph and The Guardian) in the UK media seems disproportionate.

The headlines suggesting a high protein diet is “as harmful as smoking” was not a specific finding of the study and could be seen as unnecessary fear-mongering. This is particularly of note given that the effects of a high protein diet were found to differ dramatically by age.

To be fair to the UK’s journalists, this comparison was raised in a press release, issued by the University of Southern California. Unfortunately this PR hype appears to have been taken at face value.

What kind of research was this?

This study looked at the relationship between the amount of protein consumed and subsequent risk of death among middle aged and older adults. It used data collected in a previous cross-sectional study and information from a national register of deaths in the US.

While the data used allowed researchers to identify what happened to people over time, this wasn’t the original purpose of the data collection. This means that some information on what happened to people may be missing, as researchers had to rely on national records rather than keeping close track of the individuals as part of the study.

What did the research involve?

The researchers had data on protein consumption for 6,381 US adults aged 50 and over (average age 65). They then identified which of these people died over the following 18 years (up to 2006) using national records. The researchers carried out analyses to see whether people who ate more protein in their diets were more likely to die in this period than those who ate less protein.

The information on protein consumption was collected as part the third National Health and Nutrition Examination Survey (NHANES). These surveys are designed to assess the health and nutritional status of people in the US. The participants are selected to be representative of the general US population. As part of the survey they reported their food and drink intake over the past 24 hours using a computerised system. The system then calculated how much of different nutrients they consumed.

Each person’s level of protein consumption was calculated as the proportion of calories consumed from protein. Protein intake was classed as:
High – 20% or more of calories from protein (1,146 people)
Moderate – 10 to 19% of calories from protein (4,798 people)
Low – less than 10% of calories from protein (437 people)

The researchers used the US National Death Index to identify any of the survey participants who died up to 2006, and the recorded cause of death. The researchers looked at whether proportion of calories consumed from protein was related to risk of death overall, or from specific causes. As well as overall deaths, they were also interested in deaths specifically from cardiovascular disease, cancer, or diabetes.

The researchers also looked at whether the relationship differed in people aged 50-65 years, and older individuals, and whether it was influenced by fat, carbohydrate or animal protein intake.

The analyses took into account factors (confounders) that could influence the results, including:

• age
• ethnicity
• education
• gender
• "disease status"
• smoking history
• participants’ dietary changes in the last year
• participants’ attempted weight loss in the last year
• total calorie consumption

The researchers also carried out studies to look at the effect of protein and their building blocks (amino acids) in yeast and mice.

What were the basic results?

On average, the participants consumed 1,823 calories over the day:

• 51% from carbohydrates
• 33% from fat
• 16% from protein (11% from animal protein).

Over 18 years, 40% of participants died; 19% died from cardiovascular diseases, 10% died from cancer, and about 1% died from diabetes.

Overall, there was no association between protein intake and risk of death from any cause, or death from cardiovascular disease or cancer. However, moderate or high protein consumption was associated with an increased risk of death related to complications associated with diabetes.

The authors noted that the number of people dying from diabetes-related causes was low, so larger studies were needed to confirm this finding.

The researchers found that results for death from any cause and from cancer seemed to vary with age. Among those aged 50-65, those who ate a high protein diet were 74% more likely to die during follow up than those who ate a low protein diet (hazard ratio (HR) 1.74, 95% confidence interval (CI) 1.02 to 2.97).

People in this age group who ate a high protein diet were more than four times as likely to die from cancer during follow up than those who ate a low protein diet (HR 4.33, 95% CI 1.96 to 9.56).

The results were similar once the researchers took into account the proportion of calories consumed from fat and carbohydrates. Further analyses suggested that animal protein was responsible for a considerable part of this relationship, particularly for death from any cause.

However, the opposite effect of high protein intake was seen among those aged over 65. In this age group high protein intake was associated with:

• a 28% reduction in the risk of death during follow up (HR 0.72, 95% CI 0.55 to 0.94)
• a 60% reduction in the risk of death from cancer during follow up (HR 0.40, 95% CI 0.23 to 0.71)

How did the researchers interpret the results?

The researchers concluded that low protein intake during middle age followed by moderate to high protein consumption in older adults may optimise health and longevity.

Conclusion

This study has found a link between high protein intake and increased risk of death among people aged 50-65, but not older adults. There are some important points to bear in mind when thinking about these results:
The human data used was not specifically collected for the purpose of the current study. This meant that the researchers had to rely on the completeness of, for example, national data on deaths and causes of death. This may mean that deaths of some participants may have been missed.

Information on food intake was only collected for one 24-hour period, and this may not be representative of what people ate over time. Most people (93%) reported that it was typical of their diet at the time, but this may have changed over the 18 years of follow up.

The researchers took into account some factors that could affect results, but not others, such as physical activity.

Although the study was reasonably large, numbers in some comparisons were relatively low, for example, there were not many diabetes-related deaths and only 437 people overall ate a low protein diet. The broad confidence intervals for some of the results reflect this.

Many news sources have suggested that a high protein diet is “as bad for you” as smoking. This is not a comparison that is made in the research paper, therefore its basis is unclear. While we do need some protein in our diets, we don’t need to smoke, so this is not a helpful comparison.

While the authors suggested that people eat a low protein diet in middle age and switch to a high protein diet once they get older, it is not possible to say from the study whether this is what the older participants actually did, as their diets were only assessed once.

Ideally the findings need to be confirmed in other studies set up to specifically address the effects of higher protein diets, particularly the strikingly different results for different age groups.

While certain diet plans, such as the Atkins diet or the “caveman diet” have promoted the idea of eating a high-protein diet for weight loss, relying on a single type of energy source in your diet is probably not a good idea. Consumption of some high-protein foods such as red meat and processed meat is already known to be associated with increased risk of bowel cancer.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

Links to the headlines

High-protein diet 'as bad for health as smoking'. The Daily Telegraph, March 4 2014
Diets high in meat, eggs and dairy could be as harmful to health as smoking. The Guardian, March 4 2014
Eating too much meat and eggs is ‘just as bad as smoking’, claim scientists. The Independent, March 4 2014
Eating lots of meat and cheese in middle age is 'as deadly as SMOKING'. Daily Mail, March 4 2014
Eating lots of meat and cheese could be as bad for you as smoking, report reveals. Daily Mirror, March 4 2014
Meat And Cheese 'As Bad For You As Smoking'. Sky News, March 4 2014

Links to the science

Levine ME, Suarez JA, Brandhorst S, et al. Low Protein Intake Is Associated with a Major Reduction in IGF-1, Cancer, and Overall Mortality in the 65 and Younger but Not Older Population. Cell Metabolism. Published online March 4 2014. (Open Access = FREE!)

Further reading

Press release
University of Southern California. Meat and cheese may be as bad as smoking. Published March 5 2013

Results from Paper
I've copied the Highlights and Summary from the paper.

Authors: Morgan E. Levine, Jorge A. Suarez, Sebastian Brandhorst, Priya Balasubramanian, Chia-Wei Cheng, Federica Madia, Luigi Fontana, Mario G. Mirisola, Jaime Guevara-Aguirre, Junxiang Wan, Giuseppe Passarino, Brian K. Kennedy, Min Wei, Pinchas Cohen, Eileen M. Crimmins, Valter D. Longo

Highlights

• High protein intake is linked to increased cancer, diabetes, and overall mortality
• High IGF-1 levels increased the relationship between mortality and high protein
• Higher protein consumption may be protective for older adults
• Plant-derived proteins are associated with lower mortality than animal-derived proteins

Summary

Mice and humans with growth hormone receptor/IGF-1 deficiencies display major reductions in age-related diseases. Because protein restriction reduces GHR-IGF-1 activity, we examined links between protein intake and mortality. Respondents aged 50–65 reporting high protein intake had a 75% increase in overall mortality and a 4-fold increase in cancer death risk during the following 18 years. These associations were either abolished or attenuated if the proteins were plant derived. Conversely, high protein intake was associated with reduced cancer and overall mortality in respondents over 65, but a 5-fold increase in diabetes mortality across all ages. Mouse studies confirmed the effect of high protein intake and GHR-IGF-1 signaling on the incidence and progression of breast and melanoma tumors, but also the detrimental effects of a low protein diet in the very old. These results suggest that low protein intake during middle age followed by moderate to high protein consumption in old adults may optimize healthspan and longevity.

Mark Butcher emails Michael Mosleys Horizon scientists - One meal on fast days

reposted from: http://feedfastfeast.wordpress.com/2012/08/25/grabbing-the-bullshit-by-the-horns/

crabsallover highlights, key points, comments / links.

I was not clear from the Michael Mosley Horizon film whether on the fast days you could split the 600 calories into 1 meal or up to 3 meals ie 3 x 200 cals. Mark Butcher has found that the 600 calories should be used in 1 meal. Mark Butcher emailed Longo, Mattson and Vardy from the film.

Luigi Fontana 

Advocates fasting (within the context of 24 hours) for as long as possible. He suggests that if you have to consume 5/600 calories then they should be consumed as one meal, very early in the morning so as to maximise the length of the fast.

Valter Longo

With regard to IGF-1 reduction it is better to do 4 days of (consecutive) fasting every few months and then skip meals during the week to maintain weight and try to adopt a plant based low protein diet. An alternative to the 4 days fasting is just to fast on 2 days at a time as in the 5-2 plan but you must also try to move to a healthy diet, plant based and low protein.

Krista A. Varady

With regard to how you should eat (if at all), on a fast day: So far, we have performed studies permitting people to eat 600 kcal between 12pm-2pm. We find that this strategy works well for most people (whereas a complete fast for 24 h does not). We have yet to run a study where we allow people to consume the 600 kcal as 6x100kcal (or 3 x 200 kcal) smaller meals throughout the day. However, we are planning to run this study within the next year. Krista Varady says ‘eating the 500 calorie allowance throughout the day would prevent a persons body going into a fasted state’. Since it is the fasted state that is so beneficial to us, this information is critical.

Mark P. Mattson

1. A complete fast (no food) with hydration maintained with non-caloric beverages will be superior to consuming 600 calories on the fasting days.
2. Eating the 600 calories at one meal will be superior to eating several smaller meals spread throughout the day. By eating only one meal, the body goes essentially 24 hours with no food. This results in adaptive cellular stress responses which we believe is particularly good for the brain.
3. In the case of the 5:2 diet, we do not know whether better health benefits are realized with two consecutive days of fasting versus any two days of fasting during the week.

It would be much better if you could just get through a fast day without eating at all. Obviously, very few people are able to do that, so if you are going to eat a (600 for a man, 500 for a woman) calorie reduced meal, you are much better to consume that as one meal than to spread those calories throughout the day. This is because the stress that going for 24 hours without food places on your brain actually has produced identifiable positive brain responses such as the growth of new brain cells. It’s like a workout for the brain. How to add that into an intermittent fasting or alternate day plan?

Easy. Either, take a note of what time you last ate on the feed day prior to your fast and then do not consume your 600 calorie fast day allowance until 24 hours has past. So, if you ate at 6pm on a feed day, do not eat your 600 calories until 6pm on the fast day. That way, you’ve gone 24 hours without food AND you get to eat (albeit a restricted) dinner! If that doesn’t grab you, eat breakfast on a fast day and then don’t eat again until your breakfast the next day.

Contact Mark Butcher: 

Twitter: @FeedFastFeast; FeedFastFeast Facebook Group: http://www.facebook.com/groups/feedfastfeast

On Calorie Restriction, Monkeys, Magic and Medicine

Science Writer David Stipp RSS Feed highlighted new research on Calorie Restriction in Monkeys published this week in Nature (ref 4).

1) On Calorie Restriction, Monkeys, Magic and Medicine - Compares to Wisconsin 2009 study. David Stipp comment 'CR hasn’t extended lifespan in all species, nor has it worked in certain strains of rodents. In the latest study on the topic, it failed to extend lifespan in a long-term study in rhesus monkeys at the National Institute on Aging (NIA)....the study suggested that CR improved late-life health in the monkeys, but the effect was modest and gender-specific.... dietary factors potentially gave a boost to the NIA controls’ health as they aged, which might have contributed to the fact that they were about as healthy and long-lived as the monkeys on CR in the study '

2) http://www.nature.com/news/calorie-restriction-falters-in-the-long-run-1.11297#/b1 - Nature staff writer comment 'Calorie restriction falters in the long run - Genetics and healthy diets matter more for longevity.'

3) http://www.nature.com/nature/journal/vaop/ncurrent/full/nature11484.html - Steve Austad comment

4) http://www.nature.com/nature/journal/vaop/ncurrent/full/nature11432.html - Nature Journal primary research.

5) http://www.nydailynews.com/life-style/health/low-calorie-diet-prolong-life-study-article-1.1148839 NY Daily News

6) http://www.wired.co.uk/news/archive/2012-08/30/calorie-restriction-diets - Luigi Fontana comments that possibly no effect of CR seen because monkeys were all on high protein diets. In humans, those hormones decrease only when protein intake is dramatically reduced. It's not enough to cut calories alone. "It's possible that we don't see some of the beneficial effects of longevity in these monkeys because they were on a high-protein diet," Fontana said. "The old idea is that a calorie is a calorie. When you restrict it, you have a beneficial effect. Our data and other data suggests this isn't the case. The quality of the diet matters," Fontana continued.

7) http://www.newscientist.com/article/dn22231-eating-less-fails-to-extend-monkey-lives.html Luigi Fontana believes both studies should have paid more attention to dietary composition. "Fifteen per cent of the monkey diet came from protein – that's too much," he says. "Our work suggests lowering protein, rather than calories, may be the key to increasing longevity – so reducing protein intake could have led to better results." De Campo agrees that dietary composition might play a role in lengthening life, but claims the benefits of calorie restriction are still strong. "Although we don't have the same lifespan findings as the Wisconsin group, what's really important is that we did show similar improvements in health."

8) http://www.theiflife.com/calorie-restriction-does-not-promote-longevity/ Intermittent Fasting website. Talk about lower IGF-1 levels with low protein diets.

Eat, Fast and Live Longer by BBC Horizon with Michael Mosley

reposted from: http://www.bbc.co.uk/iplayer/episode/b01lxyzc/hd/Horizon_20122013_Eat_Fast_and_Live_Longer/ (view until 17th September 2012) or thereafter on http://documentaryheaven.com/eat-fast-and-live-longer/ (accessed August 21st, 2017)

my comments and links in blue. 

Summary

http://www.bbc.co.uk/news/health-19112549 - BBC

Michael J. Mosley (wikipedia) fasted for two days every week

Michael Mosley says 'Scientists are uncovering evidence that short periods of fasting if properly controlled, could achieve a number of health benefits, as well as potentially helping the overweight.'


The Horizon editor assured me there was great new science and that I might see some dramatic improvements to my body. So, of course, I said, "yes".

I am not strong-willed enough to diet over the long-term, but I am extremely interested in the reasons why eating less might lead to increased life span, particularly as scientists think it may be possible to get the benefits without the pain. 


How you age is powerfully shaped by your genes. But there's not much you can do about that.

Calorie restriction, eating well but not much, is one of the few things that has been shown to extend life expectancy, at least in animals. We've known since the 1930s that mice put on a low-calorie, nutrient-rich diet live far longer. There is mounting evidence that the same is true in monkeys.' Source: BBC

Synopsis

From Start: Taster of this hour long Michael Mosley Horizon programme first broadcast on 6th August 2012.

Fauja Singh

@ 2 minutes: London Marathon - Fauja Singh is 101 years and the oldest marathon runner. Unknowingly he has been testing the reduced calorie diet by eating child size (ie half) portion meals for most of his life.

9m: in 1930s at Cornell University [Clive McCay] showed that mice live longer on a restricted diet

Luigi Fontana

10m: Prof. Luigi Fontana (profile & research papers eg  http://www.ncbi.nlm.nih.gov/pubmed/17482403 & http://ajpendo.physiology.org/content/293/1/E197.long, also http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2673798/ & CR Society Research (cited in The Longevity Diet by Brian Delaney and Lisa Walford) of BJC Institute of Health at Washington Uni & Salerno school of medicine studies people on severe calorie restricting diets ('these people look like a new species!') aka CRONies Calorie Restriction with Optimal Nutrition (CRON-Diet Wikipedia). Joe Cordell (twitter) has 11.5% body fat typical of a super athlete, has a 1 in a million chance of CVD (nb. myocardial infarction, stroke or heart failure are responsible for 40% deaths in UK/USA) and eats lots of fruit and veg. He only eats apple skins which have 95% of apple nutrition, the rest of an apple is sugar! Living a healthy lifestyle is fun, claims Joe!

Joe has eaten 1900 calories a day, weighs 134 pounds (cf Mike Mosley 190 pounds, 27% body fat, abdominal fat 30% - not good for his age - higher risk of CVD, stroke, cancer). If Mosley went on Joes Calorie Restriction lifestyle he would be 'cured within a year'.

[There are 100,000 CRONies worldwide (who eat food rich in nutrients but low in calories) I presume members of the CR Society International. CRONies say that body fat content should be 6-9% for men, 10-15% for females (The Anti-Aging Plan: Strategies and Recipes for extending your Healthy years by Lisa and Roy Walford, page 19)].

Valter Longo

Professor Longo has investigated growth hormone deficiency in humans

19m: Prof. Valter Longo, Uni Southern California, LA (profile & example). Experiments with a tiny mouse give 40% increased lifespan (equiv. to 120-year-old human) with genetically engineered low levels of Insulin-like Growth Factor 1 (IGF-1).

'Growth Hormone: The world record for extending life expectancy in a mammal is held by a new type of mouse which can expect to live an extra 40%, equivalent to a human living to 120 or even longer. It has been genetically engineered so its body produces very low levels of a growth hormone called IGF-1, high levels of which seem to lead to accelerated ageing and age-related diseases, while low levels are protective.' source: BBC

A 32-year-old community leader and artist who has the rare dwarfism condition (Laron Syndrome), with his bride, 17.
Source:  http://www.nytimes.com/2011/02/17/science/17longevity.html?_r=2&hpw

21m 45s: Equador - Laron Syndrome (wikipedia) & (research paper) dont get diabetes or cancer (Longo research, Sci Transl Med. 2011 Feb 16;3(70):70ra13) with images in paper.

Michael Mosley says 'Professor Longo has investigated growth hormone deficiency in humans - a similar, but natural, genetic mutation has been found in humans with Laron syndrome, a rare condition that affects fewer than 350 people worldwide. The very low levels of IGF-1 their bodies produce means they are short, but this also seems to protect them against cancer and diabetes, two common age-related diseases.

The IGF-1 hormone (insulin-like growth factor) is one of the drivers which keep our bodies in go-go mode, with cells driven to reproduce. This is fine when you are growing, but not so good later in life. There is now evidence suggesting that IGF-1 levels can be lowered by what you eat. 

Studies on calorie restrictors suggest that eating less helps, but it is not enough. As well as cutting calories you have to cut your protein intake. Not entirely - that would be a very bad idea. It's about sticking to recommended guidelines, something most of us fail to do. The reason seems to be that when our bodies no longer have access to food they switch from "growth mode" to "repair mode". 

As levels of the IGF-1 hormone drop, a number of repair genes appear to get switched on according to ongoing research by Professor Valter Longo of the University of Southern California.' source: BBC

NY Times article: 'physiology of Laron patients links up with the longevity studies that researchers have been pursuing with laboratory animals. IGF-1 is part of an ancient signaling pathway that exists in the laboratory roundworm as well as in people. The gene that makes the receptor for IGF-1 in the roundworm is called DAF-2. And worms in which this gene is knocked out live twice as long as normal.'

The single point mutation produces individuals that have very low levels of the growth hormone IGF-1. (Is IGF-1 hormone reduction good for you?) . Our cells are constantly made to divide by IGF-1 (24m) but with low levels of IGF-1 our body stops making new cells and repairs instead existing cells, DNA damage is more likely to get fixed which is why the mice and the villagers are protected from age-related diseases. High levels of protein make high levels of IGF-1 (the body is in go-go mode) (25m) and body is growing too fast for cancer and diabetes to be repaired. Eating less is not enough (26m) - you also have to cut your protein intake. You don't have to be a CRONe to lower IGF-1. Instead, fasting (plenty of water, black tea & 50 calories Cuppa-soup) for 3.5 days lowers IGF-1 and glucose levels. Michael Morley's IGF level was 210ng/ml before the fast (could increase prostate cancer risk) (33m) (normal range for humans 80-230ng/ml). After 3.5 days fast MM IGF-1 level was 110 ng/ml. MM blood glucose levels 110mg/dl (pre-fast) dropped to 80mg/dl after 4 day fast (34m). But effects will not last unless switch to a lower protein plant based diet and fast once a month to maintain benefits.

IGF-1 levels are tested by LabTestsOnline.

Krista A. Varady

Krista A. Vardy with Michael Mosley

38m: Assistant Prof. Dr Krista A. Varady (profile) the University of Illinois at Chicago. Has done research on Alternate Day Fasting (ADF) which involves 500-600 calories for men (400-500 calories for women) (25% of normal intake) on a fast day. On feed days you could eat 'whatever you want'. This ADF can result in decreased LDL, triglycerides and blood pressure levels. On the feed days, no difference in levels was found among people who had low or high-fat diets (41m). Actual consumption on feed days was only 110% of normal calorie intake (not 175% or a gorge as might be expected!) so, surprisingly, you can really tell people to eat 'whatever you want' [and however much you want] on feed days.

http://www.ajcn.org/content/86/1/7.full - Krista Vardy Review of Intermittent Fasting IF (accessed 13th August 2012) via http://www.huffingtonpost.com/andrew-weil-md/fasting-health_b_1557043.html (accessed 13th August 2012).

Vardy concluded inter alia:-

"both human and animal experiments indicate that Alternate Day Fasting ADF may effectively decrease the risk of CVD, whereas results from animal studies suggest a protective effect on cancer risk. In terms of diabetes prevention, animal data suggest a beneficial effect, but human data have been equivocal. However, it is important to note that the human studies examined in this review are limited; they all lacked control groups and used short trial lengths. Future studies with longer trials and including control groups are needed to answer these important questions.

Moreover, human ADF trials in modestly overweight persons, who are at greater risk of chronic disease, are warranted. In this context, it is important to note that the control animals in both the CR and ADF studies are likely to have been obese because they were fed ad libitum.

ADF regimens also may be as efficacious as daily Calorie Restriction CR in improving certain indexes of the risk of type 2 diabetes and CVD. Further analysis of the mechanisms responsible for beneficial effects of ADF is clearly warranted. Finally, it seems intuitively likely that persons will find it easier to fast or reduce intake on alternate days than to reduce their intake every day. For this reason, ADF regimens may allow better compliance than would CR regimens and may represent an attractive area for investigation.

It will also be important to understand whether the mechanisms by which ADF protects against chronic disease risk are similar to those of CR. Indirect evidence suggests that the 2 regimens may share mechanisms. For instance, the study of Descamps et al (26) reported increases in spleen mitochondrial Superoxide Dismutase (SOD) activity accompanied by decreases in the mitochondrial generation of Reactive Oxygen Species (ROS) as a result of ADF. Such findings suggest that ADF may act by increasing resistance to oxidative insult, which is a key feature of the stress resistance hypothesis.

In summary, this still nascent literature suggests that ADF may effectively modulate metabolic and functional risk factors, thereby preventing or delaying the future occurrence of common chronic diseases, at least in animal models. The effect of ADF on chronic disease risk in normal-weight human subjects remains unclear, however, as do the mechanisms of action. Much work remains to be done to understand this dietary strategy fully."

'Intermittent fasting (IF) (wikipedia)
Michael Mosley says 'One area of current research into diet is Alternate Day fasting (ADF), involving eating what you want one day, then a very restricted diet (fewer than 600 calories) the next, and most surprisingly, it does not seem to matter that much what you eat on non-fast days. Dr. Krista Varady of the University of Illinois at Chicago carried out an eight-week trial comparing two groups of overweight patients on ADF. "If you were sticking to your fast days, then in terms of cardiovascular disease risk, it didn't seem to matter if you were eating a high-fat or low-fat diet on your feed (non-fast) days," she said.' source: BBC

Mark P. Mattson

43m: National Institute of Ageing, Baltimore Mark P. Mattson (profile & papers) - effects of ageing on the brain. Fasting may slow onset of diseases (Alzheimers, dementia and memory loss). Mice on Intermittent Energy Restriction (IER) (Feast / fast) have equivalent to 30 years (in human terms) slower onset of Alzheimer's.

new brain neurons develop when IF regime is followed

Fasting mice have newly born brain neuron cells (46m) which are an evolutionary survival advantage if you are hungry and you can remember where the location of the food source is. Fasting exercises your brain like exercise stretches your muscles. Hunger makes you sharper. Alternate day fasting has a better outcome on the brain than daily Calorie Restriction (at least in mice, but human trials are needed to prove its true in us). Mark P. Mattson recommended MM try a 5:2 diet (48m) (5 days normal & 2 days 600 calories/day fast. Eat anytime (ie breakfast /lunch or breakfast/dinner or lunch/dinner) during the fast day (50m) for 5 weeks to see if get results (49m).

'Science is not belief, but the will to find out' (50m 34s)

5:2 feed:fast trial

In the period of filming (~5+ weeks) Mosley lost over a stone (~190 pounds to 174 pounds), total body fat reduced (27% to 19%) (53m). Luigi Fontana gave 5-week results (54m): IGF-1 reduced by 50% - enough to reduce the risk of prostate and colon cancer, blood sugar was borderline diabetic (110mg/dl) reduced to 90mg/dl (normal), total cholesterol reduced and higher HDL cholesterol. Same results as the 3.5 days fast. 

Drs Michael & Clare Mosley

Michaels wife Clare (a GP) was also delighted with his results (56m)! But more trials are needed to see whether Intermittent Energy Restriction is safe and effective. With diabetes and obesity timebomb set to explode we need as a nation a means to reverse the effects. Fasting could be the means.


Michael Mosley says 'I decided I couldn't manage ADF, it was just too impractical. Instead, I did an easier version, the so-called 5:2 diet [suggested by Mark Mattson]. As the name implies you eat normally 5 days a week, then two days a week you eat 500 calories if you are a woman, or 600 calories, if you are a man. There are no firm rules because so far there have been few proper human trials. I found that I could get through my fast days best if I had a light breakfast (scrambled eggs, thin slice of ham, lots of black tea, adding up to about 300 calories), lots of water and herbal tea during the day, then a light dinner (grilled fish with lots of vegetables) at night.  On my feed days, I ate what I normally do and felt no need to gorge. 

I stuck to this diet for 5 weeks, during which time I lost nearly a stone and my blood markers, like IGF-1, glucose, and cholesterol, improved. If I can sustain that, it will greatly reduce my risk of contracting age-related diseases like cancer and diabetes. 

Current medical opinion is that the benefits of fasting are unproven and until there are more human studies it's better to eat at least 2000 calories a day. If you really want to fast then you should do it in a proper clinic or under medical supervision, because there are many people, such as pregnant women or diabetics on medication, for whom it could be dangerous. I was closely monitored throughout and found the 5:2 surprisingly easy. I will almost certainly continue doing it, albeit less often. Fasting, like eating, is best done in moderation.' source: BBC

Info

1. http://en.wikipedia.org/wiki/Calorie_restriction (Accessed 12th August 2012)
2. http://www.theiflife.com/intermittent-fasting-101-how-to-start-part-i/  (Accessed 13th August 2012)
3. Letter to BBC from Paul McGlothin at CR Society - Mosley did not take account of his 'happiness biochemistry'!