my comments and links in blue.
Summary
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Michael J. Mosley (wikipedia) fasted for two days every week
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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.
9m: in 1930s at Cornell University [Clive McCay] showed that mice live longer on a restricted diet
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)].
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
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.
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
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).
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
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
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| Professor Longo has investigated growth hormone deficiency in humans |
'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 |
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 |
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 |
'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 |
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
- http://en.wikipedia.org/wiki/Calorie_restriction (Accessed 12th August 2012)
- http://www.theiflife.com/intermittent-fasting-101-how-to-start-part-i/ (Accessed 13th August 2012)
- Letter to BBC from Paul McGlothin at CR Society - Mosley did not take account of his 'happiness biochemistry'!
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