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REPORT - Intermi3ent Fas7ng

Intermittent Fasting & Calorie Restriction.

Can they help me live longer? Lose weight?
by Zo Harcombe

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2 SPECIAL REPORT - Intermi3ent Fas7ng

A recent UK TV programme (Monday 6th August 2012) has generated much interest about Calorie RestricKon and IntermiMent FasKng. The programme was a Horizon documentary, by Michael Mosley, called "Eat, Fast and Live Longer"1 (The comma is very important!) The programme won't be on BBC iplayer for ever and people outside the UK can't get iplayer, so let's hope YouTube copies stay up for a while2. Other people have posted the programme in parts on YouTube so do try pu[ng in the programme Ktle if the links in the reference notes no longer work.

every other day; or doing this every few days or a couple of days a week and so on. 3) The frequency with which IF is done is the nal variant. This is driven to an extent by (2) - an every other day restricKon is obviously repeated every other day. However someone can choose to fast for between one and a few days every week, every month, every quarter or as desired. The permutaKons of 1, 2 and 3 make for numerous opKons available to people interested in IntermiMent FasKng. Should anyone choose to do IF, they may be well advised to develop their own plan, taking the opKon most likely to work for them from fasKng vs. eaKng liMle, how long the fast will be and how ojen it will be undertaken.

Quick deni7ons
Let's just dierenKate between the two terms before we go any further: Calorie RestricKon (CR) is long term restricKon of calories below that needed on a daily basis by a person. As a general rule, CR involves an approximate 30% calorie decit from the daily requirement. IntermiMent FasKng (IF) should be, as the name suggests, fasKng (eaKng nothing) for periods of Kme every now and again. However, IntermiMent FasKng has come to mean many dierent things. Three things can vary: 1) FasKng does not necessarily mean eaKng nothing (drinking only water). FasKng is now taken to mean either eaKng nothing or eaKng substanKally less than the recommended intake (25% of the recommended daily calorie intake serves as a common guide). 2) The length of Kme for which IF is undertaken can vary. Some regimes have a 3-5 day literal fast (water only - or a cup-a-soup, as we will see). Other opKons include fasKng/eaKng liMle

Programme Synopsis
Just in case you can't see the Horizon programme, or if you don't have an hour to spare - here's a synopsis of the documentary. The synopsis also serves as an excellent introducKon to the whole topic of Calorie RestricKon and IntermiMent FasKng - Mosley has gone to the leading insKtuKons and met the key researchers in these elds and this is a great place to start: Michael Mosley is a great narrator and an 'up- for-it' guy. If you have seen other programmes of his for Horizon (The Truth about exercise3, 10 things you should know about losing weight4), Mosley does the experiments himself, has blood taken and gets told how much of his body is fat (too much basically!) The programme opens with Mosley meeKng 101 year old Fauja Singh who is running the London Marathon5. Mosley notes that 7,000 people in their 50s are running the London marathon and 7 people over 80. Singh took up

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running in his 80s. Singh puts his longevity down to eaKng 'child-sized' porKons. This hypothesis is not challenged. Mosley notes that "clearly genes play a signicant part" in longevity and this needs emphasis at this stage, as it is barely menKoned again throughout the programme. Mosley heads o to America and notes that life expectancy rose by "a remarkable six years" during "the darkest years of the Great Depression" (1929-1933). Mosley notes that it was at this Kme - back in the 1930s - that nutriKonists at Cornell University rst started looking at animal experiments with regard to longevity. They severely restricted how much some animals (rats) ate and found that they lived much longer. Clive McCay was the lead researcher and an arKcle about the study noted that severe food restricKon from just a+er weaning "delayed physical and sexual maturaKon and led to very large increases in maximum lifespan"6. Please note how early Calorie RestricKon was started in life and the consequence for the growth of the rats - we'll come back to this. Washington University is the next port of call for Mosley, as he meets scienKsts looking at Calorie RestricKon and longevity in humans. Professor Luigi Fontana is the man who greets Mosley at the university. (Fontana looks like a middle distance runner - very small and lean). The Washington team are looking at what they admit is severe Calorie RestricKon (CR) every single day. The researchers and parKcipants try to get opKmal nutriKon from the lower intake and this is presented as "lots of fruit and vegetables." However, anyone who knows the nutriKonal content of food knows that animal

foods beat plant foods for protein, essenKal fats, vitamins and minerals7. We meet Joe/Joseph who, for a decade, has eaten approximately 1,900 calories a day. The USA recommended calorie intake for each gender by age and acKvity level was set out in the 2010 Dietary Guidelines for Americans8. If Joe is sedentary he is esKmated to need approximately 2,000-2,200 calories per day; if he is moderately acKve he is esKmated to need 2,200-2,400 calories per day and, if acKve, he is esKmated to need 2,400-2,800 calories per day. Joe is happy to report that his brother weighs 100lb more than he does. We see Joe preparing breakfast in his kitchen - a mixing bowl size of berries with apple peel added - he throws away the non-peel part of the apple for its high sugar content. This may be sensible, but with 5.6 billion pounds of pesKcides used worldwide each year9, Joe should worry about all aspects of health. Mosley esKmates that he personally has averaged around 2,300 calories a day "quite a few of them doughnuts and burgers", he admits. Joe and Michael are both in their 50s. We don't know their heights, but Joe weighs in at 134lbs (that is Kny for a man and not very aMracKve if you don't mind a personal view) and Michael over 180lbs (they didn't give a precise number for Michael). They compete with two tests that we can do at home and then a blood test comparison. Test one is to stand on one leg with eyes closed for as long as possible. Michael can only manage a few seconds; Joe goes well past 30 seconds before they stop the test (do watch the dierent techniques though - Michael tries to hold his leg up at the height of his other knee, Joe barely lijs his foot o the oor). This tests balance, which deteriorates with age and is used here as an indicator of how 'old' someone

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is compared with the average for their age. The second test, the ruler test, is fun and simple - the two men hold their thumb and a nger slightly apart, with a ruler just above the gap. They then have to catch the ruler when it is dropped between their nger and thumb. At the age of 50 the ruler should be caught somewhere around the ve inch mark (the ruler has the starKng numbers at the top and the highest number on the ruler at the boMom). Joe manages to grab it at the four inch mark and Michael managed eight. Do try these at home! The boys then go into Fontana's oce to get their blood test results. Fontana tells them that Joe's body fat is 11.5% and Michael's is 27.1%. Looking at the full blood test results, Fontana then states categorically "Joseph isn't going to develop Cardio Vascular Disease (CVD). It's impossible to develop stroke, Myocardial infarcKon [heart aMack], heart failure." That's a bit strong - "impossible" - really?! Mosley asks what would happen to him if he followed Joe's lifestyle. Fontana answers "In a year you are going to be cured." Bit strong again in my view. O to the University of Southern California and Mosley meets Professor Valter Longo and a couple of mice. One of the mice is quite special, as he holds the world mouse longevity record. The big mouse will live approximately two years and the smaller one about 40% longer. The liMle mouse is literally a fracKon of the size of the 'normal' mouse - about one half or one third of the volume from observaKon. Mosley narrated that the liMle mouse has "incredibly low levels of a growth hormone called Insulin-like Growth Factor and it seems IGF 1 is a key factor linking calorie restricKon with longevity." Mosley then introduces the extremely rare condiKon of Laron syndrome (suered by approximately 300 people worldwide). Longo met some people in remote parts of Ecuador

with the condiKon and they reach barely up to Longo's belly buMon in height. People with Laron syndrome also have excepKonally low levels of IGF 1 - hence the impaired growth (as with liMle mouse). They also seem to be "virtually immune" to diabetes and cancer. The programme actually doesn't menKon longevity in relaKon to these Ecuadorian villagers. The implicaKon is clearly that the avoidance of major killers, such as diabetes and cancer, means that people with Laron syndrome live longer, but the programme doesn't claim this and other evidence suggests that this is not the case. "Unlike dwarf mice, however, people with Laron syndrome do not seem to experience increased longevity" is a statement from an arKcle in which Longo was involved10. Mosley's voiceover states: "Our bodies are constantly in 'go-go' mode. Our cells driven to divide by IGF 1. But when IGF 1 levels drop our cells shij into a completely dierent mode. The body slows producKon of new cells and starts repairing exisKng ones instead. DNA damage is more likely to get xed and that's why the mice and the villagers are protected from age related diseases." Mosley conKnues: "It turns out that there's something in the food we eat that aects how much IGF 1 our bodies produce. That something is protein. When we eat a lot of protein, our cells get locked in 'go-go' mode." No evidence for protein being the precursor of IGF 1 is oered by the programme - this is simply stated as fact. Mosley asks "So - how do you reduce your IGF 1?" "Studies on calorie restricKon suggest that eaKng less helps but it's not enough. As well as cu[ng calories, you have to cut your protein

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intake." Again - no evidence is oered for this asserKon. Longo advises Mosley to try a 3.5 day fast, which he does (he actually has a disgusKng 50 calorie cup-a-soup each day). Longo explains that even a 24 hour fast can reduce glucose levels and levels of IGF 1. Mosley had his blood levels of IGF 1 measured before and ajer the fast. (Mosley had had his IGF 1 blood levels measured at 28 nanomoles/litre in the UK before leaving for America). The normal human value for IGF 1 in America is approximately 215 ng/ml and Mosley is there or thereabouts before the fast. Ajer the fast, Mosley's levels fall to approximately 115 ng/ml. (The UK/USA conversion factor for IGF 1 is - to convert ng/ml to nmol/L mulKply by 0.131 and to convert nmol/L to ng/ml divide by 0.131). Chicago is the next stop for Mosley and he meets Dr Krista Varady. Mosley has already decided that he doesn't ever want to do the four day fast again. Varady is studying Alternate Day FasKng (ADF) with humans. Women have 400-500 calories every other day and men have 500-600 and the day in between the subjects are supposed to eat whatever they want. At about 39 minutes into the programme Varady bangs on about good and bad cholesterol, which loses the programme overall credibility. (Cholesterol is cholesterol. There is no good or bad version. LDL and HDL are not even cholesterol - they are lipoproteins). Varady concluded that it didn't maMer if people had a low fat or a high fat diet on the 'feed' day. The key thing was to have the very low calorie day. She also observed that, even though people had approximately 25% of normal calorie intake on the 'fast' day, they didn't compensate by having 175% of calorie intake on the 'feed' day. Varady took Mosley to a drive through fast-food junk restaurant on the feed

day. Not exactly role model nutriKonal behaviour. Mosley's nal desKnaKon was BalKmore where he met Professor Mark MaMson at the NaKonal InsKtute on Aging and another special mouse. The mouse is exploring a maze to try to remember where he saw food. The mice being studied are desKned to develop Alzheimer's disease. When these mice are put on a diet of feast days and fast days they live without obvious signs of Alzheimer's for six months to a year longer than they would otherwise have done. Mosley likens this to humans ge[ng Alzheimer's at the age of 80 rather than at the age of 50. When the mice eat what is wrongly described as a high fat diet they develop Alzheimer's much earlier. MaMson says "when we put fructose in their drinking water, that has a dramaKc eect. The animals will have an earlier onset of the learning and memory problems - 3-4 months sooner." Mosley equates the fructose impact to developing Alzheimer's in one's 30s or 40's - not even as late as the age of 50. Fructose is, of course, sugar and zero fat content. Another common error that impacts overall credibility of the programme. Mosley asks MaMson what's going on. The brains of the fasKng mouse showed that "sporadic bouts of hunger encourage new neurons to grow." The raKonale is given by MaMson in evoluKonary terms that - if you're hungry, having the cogniKve ability to remember where you last saw food gives a survival advantage, so the Mest develop this and survive. I found this plausible but, as MaMson himself says, this needs to be tested in humans. We cannot make assumpKons from observaKons in mice.

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"Hunger really does make you sharper" says Mosley. He's convinced already. MaMson believes that ADF has beMer eects on the brain than a lower amount of daily Calorie RestricKon. This is based on his work with mice and he again admits that this research now needs to be extended to humans. Mosley's nal experiment was to try something recommended by MaMson: ve days of normal eaKng and two days at 600 calories a day. Mosley did this when he got back to the UK - ajer rst having another IGF 1 blood test. This one was even higher than his 28 nanomoles/ litre before he lej for America. This suggests that any benet of the 3.5 day fast did not last. Ajer ve weeks on this 5/2 diet, Mosley had lost over a stone (measuring at 173.8lbs) and his body fat percentage had gone below 20%. IGF 1 had dropped by 50%. Mosley talked about his reducKon in total cholesterol and increase in 'good' cholesterol and his GP wife, of course, didn't correct him. That's the synopsis. Let's look at the logic of the programme to see what it may or may not have proven...

Q2) Has it been proven that Alternate Day F as K n g ( AD F ) red u ces h u man ri s k o f Alzheimer's? No. Some mice have shown delayed cogniKve impairment with ADF and accelerated cogniKve impairment with fructose intake. The impact of fructose needs to be isolated from the impact of ADF and the whole topic needs to be researched in humans. Q3) Has it been proven that trying to lower IGF 1, ajer reaching normal growth maturity, increases longevity in humans? No. Those with Laron syndrome have substanKally lower levels of IGF 1 from birth and do not develop to average human height. Mice with severe Calorie RestricKon post weaning have substanKally lower levels of IGF 1 and do not develop to average mouse size. Q4) Has it been proven that reducing protein intake reduces IGF 1 (notwithstanding that the programme has not proven longevity impact of this in humans)? No. One subject (Mosley) fasted for 3.5 days and thus reduced calories, vitamins, minerals, carbohydrate, protein and fat simultaneously. Blood levels of IGF 1 dropped in this one subject at the end of the 3.5 day fast, as did glucose blood levels and as did probably blood levels of any measure. Q5) Has it been proven that fasKng for a few days reduces IGF 1? In one subject in the short term, yes. In the same subject, in the medium/longer term, no (blood levels were above the original levels ajer returning to the UK). Q6) Has it been proven that Alternate Day FasKng (ADF) impacts IGF 1 in humans? No. This was not tested in the programme.

Logic of the programme

Q1) Has it been proven that lowering IGF 1 makes humans live longer? No. The humans with Laron syndrome have "virtual immunity" from diabetes and cancer, but no evidence of dierent longevity. No other human study was referenced by the programme (I am not aware that one exists) where IGF 1 has been lowered in humans for a long enough period of Kme, against a comparator control group, to measure longevity.

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Q7) Has it been proven that Calorie RestricKon every day impacts IGF 1 in humans? No. This was not tested in the programme. Q8) Has it been proven that ve days of normal eaKng followed by two very low calorie days a week impacts IGF 1 in humans? In one subject ajer ve weeks, yes. Which takes us back to: Q1) Has it been proven that lowering IGF 1 makes humans live longer? No. My overall conclusion therefore is that this was an interesKng and enjoyable introducKon to a number of topics, but it proves virtually nothing.

"Did the two correlate? Yes, but minimally. Each study showed a minor eect. The Framingham Study, the most comprehensive of the three, found about a 6 percent correlaKon between life span of the parents and life span of their ospring, meaning that many other factors aect longevity as well. If both your parents lived past the age of seventy-ve, the odds that you will live past seventy-ve increase to some extent. But to what extent? "If you are a man and both of your parents died before the age of seventy-ve, then your Real Age (physiologic age) will be as much as 4.2 years older. If you are a woman, your Real Age will be as much as 3.5 years older. If both parents lived past the age of seventy-ve, then your Real Age will be 4.2 years younger if you are man, and 3.5 years younger if you are a woman. If no rst-degree relaKve (parent, brother, sister) had breast, colon, or ovarian cancer diagnosed early, you are an addiKonal 0.2 to eleven years younger than if your siblings or parents had those diagnoses. Some geneKc condiKons, such as being a carrier of the BRCA-1 breast cancer gene, can make your Real Age as much as 17 years older. This is one of the instances where geneKcs can make a big dierence." I found this interesKng, as I would have expected a stronger correlaKon between life span of parents and life span of their ospring. It just shows that lifestyle and environment remains a very important determinant. Let's now look at Calorie RestricKon and I n t e r m i M e n t F a s K n g a w a y f r o m t h e programme...

There's a topic I want to briey cover - some of you may wish to do further research on this - and that is the menKon of geneKcs early on in the programme. The age of your parents - especially your same gender parent - can aid as a predictor of your longevity. Our children are likely to be the rst generaKon that don't outlive their parents - a legacy of the obesity, diabetes, fake food, modern lifestyle. However, if you eat like your grandparents ate, you have a good chance of living longer than your same gender parent. Only three major studies have looked at the correlaKon between longevity of parents and their children. The Framingham Study was one; The Longevity Study was another (also known as "Terman's Termites" study) and the Alameda County Study. I have not reviewed these studies personally, but Dr Michael Roizen asks if parent and ospring longevity correlate and summarises the ndings as follows in his book The Real Age Makeover:

The work of the 1930s on Calorie RestricKon preceded and may have inspired, some work in

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the 1940s on IntermiMent FasKng. A 1945 study called Apparent prolongaKon of the life span of rats by intermiMent fasKng by Anton J Carlson and Frederick Hoelzel11, references and builds upon McCay's work. This arKcle references one human experiment done by a man called Coronaro who lived from 1464 to 1566 and aMributed his longevity to "rigid restricKon of food intake." Carlson and Hoelzel recognise that prolonged calorie restricKon is unlikely to occur while "sucient palatable food is easily aMainable". Thus they started to look at IntermiMent FasKng as an alternaKve to Calorie RestricKon. They noted a study done in 1934 (Robertson, Marston and Walters "The inuence of intermiMent starvaKon and intermiMent starvaKon plus nucleic acid on the growth and longevity of the white mouse".) In this study, 24 male and 24 female mice were fasted 2 successive days in 7 (this is interesKng - it's the Mosley 5/2). The average life span of the fasted males was 745 days while that of 24 controls was 712 days (5% dierence). The average for the fasted females was 819 days while that of 24 control females was 773 days (6% dierence). "The prolongaKon of life was not regarded as signicant by Robertson and his associates". The study reported that pepKc erosion or ulceraKon of the stomach and duodenum was found in some mice (and young rats) ajer single periods of starvaKon of 36 hours or more. Worth noKng! Carlson and Hoelzel's own study improved in design by having mice from the same liMer in dierent study groups - a beMer like-with-like comparison. Their own study compared 33 rats allowed as much food as they wanted with groups of 37, 37 and 30 rats that were fasted 1 day in 4, 3 and 2, respecKvely - from the age of 42 days. Their results showed that the apparent

life span was increased by the IntermiMent FasKng. The opKmum interval for fasKng appeared to be fasKng 1 day in 3 and this increased the life span of males from the same liMer about 20% and females from the same l i M e r a b o u t 1 5 % . H o w e v e r , t h e p r e - experimental condiKon of the individual rats was also found to be an important factor determining the life spans. The original work on IntermiMent FasKng and Calorie RestricKon was therefore done from a longevity perspecKve can it make animals live longer? More recent studies are looking at the same issue - longevity. We'll therefore concentrate on possible longevity benets for now and look at possible benets for weight later on in this arKcle. A Calorie RestricKon study has been done on the Rhesus monkey (started in 1987) to use an animal closer to humans for a study subject. The study was done by the NaKonal InsKtute on Aging - one of the insKtuKons visited by Mosley12. The monkeys were given a 30% calorie restricKon. The interesKng part of the conclusion for me is: "We have observed physiological eects of CR that parallel rodent studies and may be predicKve of an increased lifespan. Specically, results from the NIA study have demonstrated that CR decreases body weight and fat mass, improves glucoregulatory funcKon, decreases blood pressure and blood lipids, and decreases body temperature. Juvenile males exhibited delayed skeletal and sexual maturaKon... Although 81% of the monkeys in the study are sKll alive, preliminary evidence suggests that CR will have benecial eects on morbidity and mortality. " The study is therefore observing improvements in health indicators and extrapolaKng these to

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predicted increased lifespan. Lower weight, decreased body temperature etc may extend life, but we don't as yet know this in primates, let alone humans. Even if we nd conclusive evidence - can humans live in the modern world day-ajer-day consuming almost one third fewer calories than we need? Heilbronn and Ravussin reviewed the literature available in 2003 in the arKcle "Calorie restricKon and aging: review of the literature and implicaKons for studies in humans."13 They concluded: "Calorie restricKon (CR) extends life span and retards age-related chronic diseases in a variety of species, including rats, mice, sh, ies, worms, and yeast. The mechanism or mechanisms through which this occurs are unclear." The longest running scienKc study of CR in primates was begun at the University of Wisconsin in 1989. A recent publicaKon from that study was called " Caloric restricKon and aging: studies in mice and monkeys."14 As recently as 2009, study authors Anderson, Shanmuganayagam and Weindruch were sKll staKng that possible mechanisms were unknown: "It is widely accepted that caloric restricKon (CR) without malnutriKon delays the onset of aging and extends lifespan in diverse animal models including yeast, worms, ies, and laboratory rodents. The mechanism underlying this phenomenon is sKll unknown. We have hypothesized that a reprogramming of energy metabolism is a key event in the mechanism of CR (That was Anderson and Weindruch's hypothesis in 2007)... " I have seen this hypothesis elsewhere. The idea is that restricKng food intake so substanKally slows the animal's metabolism that this has direct benet on longevity. Higami et al. 2006

suggested that long term Calorie RestricKon may down regulate approximately 50 inammatory genes. This would be a plausible and important pathway. Simpler explanaKons are that the lower metabolism puts less strain on all systems in the body - digesKve, endocrine (hormones), circulatory, lymphaKc, immune system and so on and that this alone enables the body to funcKon for longer. The fact remains that there has not yet been a long-term, randomized clinical trial of CR or IF in humans, so we cannot know whether or not CR or IF prolongs human life. I do not anKcipate that such trials will be done involving Calorie RestricKon, not least because I cant think of many humans who could tolerate about one third of the food intake that they need for any period of Kme. We have The Minnesota StarvaKon Experiment15, but this only involved a period of 24 weeks of calorie deprivaKon thats not long term Calorie RestricKon - and the outcomes for general well being in this important study were not good. Some groups of ChrisKans, Buddhists, or other people who eat relaKvely liMle for religious reasons, may be the closest that we can get to observing prolonged periods of fasKng or Calorie RestricKon and the eect on humans. Anecdotally, we do see elderly monks and elders of communiKes (evidence of longevity), but this has not been quanKed in research, standardised against other comparator groups and there are so many other factors to take into account with these groups of people that this cannot be viewed as scienKc. Not least the lack of stress and having no mobile/ipad and email in such communiKes probably adds years to ones life. Researchers at the Intermountain Medical Center in Utah reported in 2007 and April 2011 that fasKng, (not eaKng and drinking only

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water), for 24 hours may be linked to a lower risk of heart disease and diabetes. The most recent study was published in April 201116. The study was done over one 24 hour period! In the second (2011) study, the subjects were monitored for another 24 hours as they returned to normal eaKng. Blood tests were taken and it was found that triglycerides, weight and blood glucose levels dropped during the fast - no surprise there. This was then extrapolated to conclude that a) this would conKnue if this experiment were repeated (not eaKng for 24 hours) and b) that this would lower overall risk of heart disease and diabetes. The 2011 study interesKngly found that, as triglycerides fell so LDL and HDL increased (by 14% and 6% respecKvely) and total cholesterol increased. I don't care about blood cholesterol levels, but no doubt people measuring them do. Human Growth Hormone also increased - interesKng in the context of IGF 1 above. I can see some logic for a number of ways in which IntermiMent FasKng and/or Calorie RestricKon could have health benets: 1) We know that high levels of glucose in the blood are dangerous Gary Taubes and Robert LusKg even use the term toxic. The less we dump lots of glucose into our blood stream, and the less ojen we do this, the beMer this has to be. I ojen think of Type 2 Diabetes as the body saying enoughs enough I cant cope with this glucose/release insulin/get the balance just right kind of challenge any longer Im packing up. It also follows that by not over-working this mechanism, we will achieve benets for our health. 2) The liver, kidneys and heart generally will be less taxed by someone eaKng less and/or less ojen. They have less to do and can, arguably, perform other funcKons more freely without having to deal with food all the Kme. (The liver

has approximately 500 funcKons to perform within the body. I can see how it would appreciate a day o from metabolising food every now and again.) 3) There is clearly an evoluKonary argument that we would not have been able to eat the amount of food that we can and do today and hence we have not evolved to eat with the regularity and quanKty that we currently do. Our eaKng paMern would more accurately have been called IntermiMent EaKng in the past - the fasKng would have been the status quo - parKcularly so during the lean winter periods. 4) Much emphasis is placed in literature on IF or CR that the food consumed must be highly nutriKous to compensate for the reduced intake. This alone may have some benet. The CR person whom Mosley met - Joseph - would be most unlikely to consume empty (sugar/ our) calories and therefore another health benet pathway could be that people who eat less may eat beMer. This does need to be measured against any loss of nutrients from reduced food intake. I have not seen any menKon of this in the IF/CR literature, let alone a study thereof. If humans are following the Chicago/Dr Varady Alternate Day FasKng and having burgers and chips on the 'feed' day and 600 low fat/high carbohydrate calories on the 'fast' day, they will highly likely miss out on essenKal fats, protein, vitamins and minerals. There will be health consequences of this that need to be factored in. If someone wants to try CR or IF, I would recommend IF over CR. Like Carlson and Hoelzel from the 1940s, I don't think that prolonged Calorie RestricKon is widely achievable while "sucient palatable food is easily aMainable". I also worry that CR is so similar to The Minnesota StarvaKon Experiment that I cannot see how a dierent outcome would ensue. With

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CR, I would anKcipate hunger, food obsession and any modern human, living freely, would do what the Minnesota men would have done had they not been imprisoned eat, overeat and regain any lost weight and more and lose any possible health benets. If you want to do IF because you think it will make you live longer, I have three thoughts for you to consider: 1) There has not yet been a long-term, randomized clinical trial of CR or IF in humans, so we cannot yet know whether or not CR or IF prolongs human life; 2) Any benets observed in animals have been from such a young age that growth overall has been stunted. a) I assume that you would rather be Arnie Schwarzenegger than Bob Hoskins in stature (although, interesKngly, you may favour Kylie over BrigiMe Nielsen) and b) we do not know how much of the observed longevity is connected to the growth impairment. Either way - if rodents have been observed to 'enjoy' a 5-30% increased life expectancy having undergone CR or IF from post weaning, don't extrapolate this to you being fully grown and maybe in your 30s, 40s or even 70s and think that you can enjoy any such measurable extension in life expectancy. 3) There are many other ways in which it is suggested that humans can enjoy a healthier life for longer, if not live longer. I would recommend that people achieve all of these before starKng to cut back on food intake - not least with the nutriKonal impact unexplored, let alone known. The widely accepted health goals are: don't smoke; don't drink excessively; don't eat junk food; avoid trans fats; minimise exposure to chemicals and polluKon; minimise stress; keep the mind and body acKve; love and

be loved; get enough sleep and have something that gives your life meaning and purpose. Not only do we need evidence for any benet of CR and/or IF, ideally we would have any benet weighed up against these other health markers so that we could prioriKse our goals. Just before we move on, in July 2012 I came across very interesKng UK data for life expectancy and healthy life expectancy17:
England Scotland Wales 2008-2010 average life expectancy 2007-2009 average healthy life expectancy Men 78.6 75.9 80.4 60.1 63.5 77.6 81.8 62.5 62.8 Women 82.6 Men 63.5

Women 65.5

The most fascinaKng numbers of all were even more regional than this - as the report noted: "There was also considerable variaKon in life expectancy at birth across the English regions. Average life expectancy, for men and women, was highest in the South East (79.7 and 83.5 years respecKvely) and lowest in the North West (77.0 and 81.1 years). At local area level across the UK, average life expectancy at birth varied by 13.5 years for men (85.1 years in Kensington and Chelsea in London compared with 71.6 years in Glasgow City) and by 11.8 years for women (89.8 years compared with 78.0 years for the same areas)." If you were born in Kensington and Chelsea, you have an incredible 13.5 years and 11.8 years advantage over your Glaswegian male and female comparators respecKvely. This reminds us that poverty and locaKon also have a signicant bearing on longevity and years of good health. So forget starving and make sure that you're female and born in a posh place!

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12 SPECIAL REPORT - Intermi3ent Fas7ng

Intermi3ent Fas7ng & Weight Loss

Some of you may be interested in starving for the rest of your life, to try to extend your Kme on this planet by some unknown and immeasurable period of Kme, but, working in the eld of obesity as I do, many of us are just as, or even more, interested in weight loss... Having read Keys' Biology of Human StarvaKon (The Minnesota StarvaKon Experiment),18 I'm not going to discuss Calorie RestricKon at all in this secKon on weight loss. I have only seen evidence that even short to medium term aMempts, let alone long term eorts, to conKnually create a calorie decit result in weight gain to and then beyond the original starKng weight. The physical and psychological eects of sustained calorie deprivaKon are well documented in this invaluable study: faKgue; hunger; depression; muscle wasKng; hair loss; cogniKve impairment; inability to concentrate or funcKon; loss of sexual desire; obsession; loss of perspecKve and so on. This is not a scenario anyone should consider embracing without reading this great and comprehensive study. IntermiMent FasKng may, however, have some benet for those trying to lose weight... Unless you are raiding the fridge in the middle of the night, you are already fasKng while you are asleep. My husband, Andy, and I tend to have dinner around 6pm and have usually nished eaKng for the day on most days by 7pm. Occasionally we'll have some berries and/ or yoghurt ajer the dog walk, at around 9.30pm, but we ojen go from 7pm to 7am (ajer the rst dog walk of the day) without food. We are therefore fasKng for 12 hours a day, but we dont think of it as a fast or a hardship its just bed Kme.

Michael Eades has done an interesKng blog on IntermiMent FasKng19 where he and his wife Mary have trialled fasKng for 24 hour periods. Dr Eades describes how they seMled on a 6pm cut-o Kme so that they didnt eat from 6pm one day to 6pm the next and this meant that they could eat up to 6pm one day and ajer 6pm on another day thus never having a whole day when they ate nothing. This is a good idea if you want to try a 24 hour no-food fast. Dr Eades makes references to rat studies where IntermiMent FasKng was taken to mean not eaKng on one day and eaKng freely on the next - i.e. Alternate Day FasKng. Eades states that the rats made up for the starvaKon on the eaKng days, taking in a similar number of calories in total. I could not nd evidence for such calorie 'restoraKon' in literature that I reviewed. There is liMle menKon in this blog of any impact on weight experienced by the Eades. The one relevant sentence says: Over the period that we followed the various IntermiMent FasKng regimens we lost a liMle weight because, unlike the rodents, we couldnt eat twice as much during the eaKng days as we would have eaten were we not fasKng. Mark Sisson also did a blog on IntermiMent FasKng20 and menKoned his gym buddy, Syd, who fasts every Tuesday he doesnt eat ajer dinner on Monday unKl breakfast on Wednesday. Art De Vany also recommends IntermiMent FasKng and it is regularly discussed on Paleo forums, but, there is liMle in the way of hard and fast rules and results. You wont nd a do this and this ojen and this will happen. This is only to be expected there is no formula for weight loss, full stop, so there can be none for this tool in the weight loss tool kit. It will sadly have to be something that someone tries for themselves and sees if it makes a dierence.

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13 SPECIAL REPORT - Intermi3ent Fas7ng

Later in the same Dr.s Eades blog there is an interesKng reference to a study published in the Medical Hypothesis Journal in March 2006. Dr Laub experimented with an IntermiMent Fast whereby he and two colleagues ate whatever they wanted on non-fast days and consumed about 20-50% of their esKmated daily energy requirements on the fasKng days. Dr Eades notes the many health benets, but there is no menKon of any impact on weight. How frustraKng! Dr Laub refers to a 1957 paper where subjects were alternaKng between 900 and 2,300 calories averaging 1,600 calories and maintaining weight. The subjects were elderly (in a residence for old people) and, again, many and various health benets were noted, but only that weight was maintained. Those trying IntermiMent FasKng for weight loss will want to lose, not maintain, weight having to starve every other day.

intake by about 3,500 calories to lose 1lb of fat, that means Id lost just over 2lb of ab." He should have made the connecKon that Joe, with his daily decit of anywhere between 200 and 700 calories a day, should be losing between 21 and 73lbs in fat alone each and every year (more on top in terms of water and lean Kssue). Given that Joe has been doing this for a decade, he should have been dead years ago! I share this point in the weight loss secKon to remind people that the calorie formula is completely lacking in evidence22. 2) IntermiMent FasKng OpKon 1: A four day fast, which is advised to be done every couple of months. This is what Mosley did and doesn't want to do again - I don't blame him. 3) IntermiMent FasKng OpKon 2: The Chicago team were looking at ADF - Alternate Day FasKng. The idea of this is that women have 400-500 calories a day and men 500-600 calories a day on the fasKng day and you eat whatever you want on the 'feed' day. This sounds worryingly like binge/starve syndrome to me, otherwise known as bulimia. 4) IntermiMent FasKng OpKon 3: The 5/2 system - 5 normal days eaKng and 2 low calorie days with approximately 600 calories a day. This was the opKon most favoured by Mosley.

Calorie Restric7on & Intermi3ent Fas7ng op7ons

There were four opKons presented in the Horizon programme - one for Calorie RestricKon and three IntermiMent FasKng opKons. These are a good place to start: 1) Calorie RestricKon was what Joe was doing in the Horizon programme - living on 1,900 calories a day. If Joe were sedentary he would have a decit of approximately 200 calories a day, if moderately acKve it would be approximately 400 calories a day and the decit would be approximately 700 calories a day if Joe is acKve. In a recent arKcle21 Mosley pledges his allegiance to the 3,500 calorie formula. Referring to his 3.5 days fast he says: "At the end, I had missed out on about 7,500 calories worth of meals. Since you need to cut your food

Weight loss - back to basics

What we want to do is to achieve any possible benets of IntermiMent FasKng without having to go to extremes. Lets go back to basics, therefore, and think about what were trying to achieve. We are trying to lose weight. This means that we are trying to break down triglyceride. We know that there are two circumstances in which this can be done the brain can demand the glycerol (glucose) part of triglyceride for fuel and/or the body can

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14 SPECIAL REPORT - Intermi3ent Fas7ng

demand the fat part of the triglyceride for fuel. We also know that breaking down triglyceride can (to all intents and purposes) only be done when there is insucient glucose or glycogen available. If glucose is available, the brain and body will both use this preferenKally for fuel. Hence, on The Harcombe Diet23, we run on low glucose levels all the Kme and we dont graze all day long, so that we have decent periods of Kme each day when our body can burn our own body fat. The well worn plaKtude "eat less/do more" seems to have some logic surely if we just eat less the body has to burn body fat. The body, of course, can and does adjust and us eaKng less will most likely just lead to the body doing less acKvity and/or less basal metabolic acKvity so that the eaKng less is just absorbed in doing less. We need to make a demand on the bodys need for fuel somehow, without the body just doing less and/or trying to get us to eat more to compensate. So, we are trying to get the body to burn fat. The raKonale would be its one thing to give the body no reason not to burn fat its another to try to encourage it to do so. Note not force, but encourage. We should always hold true the principle that we need to work with our body and never against it. It makes sense that our body will funcKon beMer if we can encourage our fat storing and fat burning mechanism to work well both ways. Clearly, in anyone with a weight problem. the fat storing mechanism has been working well! The fat burning process has not been working so well especially if we have been counKng calories and eaKng more carbohydrates. This is where IntermiMent FasKng may be able to deliver the biggest weight loss benets, se[ng any health benets aside for now. Having this key mechanism working opKmally in

both direcKons can only be benecial for weight loss. The more we can encourage fat burning to occur, the more natural it should become for the body. We have no evidence for this, but the logic is surely clear. This is the thinking behind IntermiMent FasKng and it has evoluKon on its side. Remember Mark Sissons character Grok? The Grok family is used in Primal Blueprint24 to depict the cave family and how they would have lived. The Grok family would undoubtedly have skipped meals and had to go without food for many and long periods of Kme. If glycogen is available the body will use this for energy. If it isnt, the body is likely to make the person do less to compensate, but it can also draw on fat reserves if necessary. Groks body would have been well tuned to storing and burning fat his survival depended on it. The signicant dierence between modern man and Grok is that Grok had no choice but to go without food for periods of Kme. It is tough not to be able to nd food, but arguably tougher to be surrounded by food and to have to consciously not eat.

How to fast intermi3ently

There are ve key things to think about before you try IntermiMent FasKng in the context of trying to lose weight: 1) If it aint broke, dont x it. If you are currently doing well with your weight loss sKck with what youre doing dont play around with things like IntermiMent FasKng unless you need to. 2) You must have a regular base from which to start. It is criKcal that you have had a period of Kme where you eat regularly before trying

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15 SPECIAL REPORT - Intermi3ent Fas7ng

IntermiMent FasKng. The body needs to be in the state where it knows it gets regular healthy fuel and be working with you before you start playing with the rules. On The Harcombe Diet22, we make a point of ge[ng you into the habit of three regular meals a day for a period of Kme. We ojen quote the rule of thumb that it takes approximately 21 days to form a new habit, so we need to eat three regular meals a day for at least this length of Kme and ideally longer for your body to realise that you are no longer calorie counKng or bingeing and starving you are regularly nourishing your body and without fail. At this point, your body is going to be ne missing the odd meal. Dont miss a meal regularly or the body will adjust to the new paMern but the odd one here or there and the body wont think youve gone back on some daj diet. It may slow you down a bit, but it will just as likely use fat reserves and thats what we want it to do. 3) You must have stable blood glucose levels before you fast. It is criKcal that your blood glucose level is stable before trying IntermiMent FasKng. If you nd that a porridge breakfast leaves you hungry late morning, then this is not the ideal meal to have before trying to skip a meal. If you have a carb breakfast and then decide to skip lunch, you may well have a blood glucose high very soon ajer the porridge and then a blood glucose low about 90-120 minutes ajer. Even a slight high and low may make your blood glucose level insuciently stable to try IntermiMent FasKng. Skipping a meal when your blood glucose level is low is not healthy or likely to be achievable. You are likely to be in a state of low blood glucose (hypoglycaemia) and your body will be crying out for food. You will get all

the bodys symptoms of hypoglycaemia as it tries to get you to eat shaky hands, irritability, cant concentrate, thinking about food all the Kme, headaches, light headed feeling and so on. You have a low chance of being able to resist this onslaught from the body. As long as you skip a meal when your blood sugar is stable (e.g. miss lunch ajer a saKaKng egg and real bacon breakfast), there is no reason for you to have a hypoglycaemic episode. Do watch out for hunger earlier than normal for dinner and make sure that you dont get so hungry that you start eaKng the wrong things before your healthy dinner. 4) It is important not to make this regular, or the body will just adjust. If you always miss breakfast, the body just doesnt kick start your metabolism for the day unKl you break your overnight fast (thats why its called break-fast). IntermiMent FasKng will work best if/when it happens naturally if you try to plan it you may make it regular, you may compensate in advance if you think you are going to miss a meal. If you nd you have been so busy that its 2pm and you havent had lunch and you dont feel hungry (because you had a great breakfast) go with it and have an early and good dinner and you should have been burning fat during the day. If youre late home from work and Kred just go to bed early and dont have a disturbed nights sleep by eaKng too late and having to digest food while youre trying to sleep. 5) It is important to approach this with the right mindset. This is why natural it just happened meal skipping has got to be beMer than planned missed meals. There will be a tendency to

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16 SPECIAL REPORT - Intermi3ent Fas7ng

compensate in advance and in retrospect if the missed meal is more planned. IntermiMent FasKng needs to come with a posiKve mindset not a deprived mindset. You need to be thinking this is a great opportunity to encourage some fat burning, not thinking Im going to be hungry and feel like Ive missed out. If you nd that you are eaKng so much more at other meals, just because you missed one, or you nd that this starts reawakening an unhealthy preoccupaKon with food, then this is not healthy for you. If you nd that it makes you feel mentally alert and that you enjoy the occasional feeling of hunger and the enhanced enjoyment of the meal that follows, this could be a new tool in your kit bag. If you want to try IntermiMent FasKng, I recommend skipping meals, as and when it can naturally be done and when your blood glucose levels are stable and if you have the right mental approach to it and not in other circumstances. As a suggesKon for how ojen if you need something to kick start your weight loss, you may benet from naturally skipping one or two meals a week. Its another opportunity to get your body to burn fat.

Studies on animals have been encouraging, but with the strong caveats that a) the experiments were started very young and growth was substanKally impaired; b) the animals were contained and not subject to the temptaKons of 'free range' humans and c) the mechanism by which any benets may be occurring is not known. The Horizon programme suggested that IGF 1 may be the key factor and that protein in turn may be the key determinant of IGF 1. The programme proved neither. We have suggested a number of plausible benet pathways in this arKcle: less strain on the systems of the body; reduced and/or less frequent consumpKon of glucose/fructose (although this can be achieved without fasKng); beMer aMenKon paid to overall nutriKon while eaKng less at Kmes etc. The Minnesota Experiment tells us that Calorie RestricKon - an approximate 30% calorie decit over a long period of Kme - is likely to have d e l e t e r i o u s e e c t s o n p h y s i c a l a n d psychological well being. I could not recommend this personally. Joe in the Horizon programme and Victoria Beckham appear to be rare beings in managing this! There is no conclusive evidence that IntermiMent FasKng has been shown to have a sustained benet for weight loss. However, there is a logic that encouraging the body's fat burning mechanism to do its work will have a benet. There may be other benets, such as people feeling more inclined to eat beMer overall when they are pu[ng quite a bit of eort into a form of IF on occasions. There are no set rules for IntermiMent FasKng and no agreement on the opKmal opKon. There is some logic that 5/2 will be easier (and therefore more likely to be adhered to) than

The studies into IntermiMent FasKng to date have been much more about health benets than weight loss (and indeed the Calorie RestricKon studies seem to have been exclusively focused on health benets). The fact remains that there has not yet been a long- term, randomized clinical trial of CR or IF in humans, so we cannot know whether or not CR or IF prolongs human life (or achieves sustained weight loss).

Copyright Zo Harcombe 2012. The Harcombe Diet PRO Plan

17 SPECIAL REPORT - Intermi3ent Fas7ng

Alternate Day FasKng. FasKng for a few days at a Kme seems to be generally regarded as challenging, to say the least, by those who try it. The opKon chosen by the Eades and Mark Sisson's gym buddy seems a good one for a 24 hour fast - start ajer dinner one day and then there is no whole day when no meal is eaten. The three variables to consider for IntermiMent FasKng are: 1) How much food - none vs. approximately 500-600 calories a day; 2) How long this is done for - days vs. 24 hours; and 3) How ojen this is repeated - every other day or a longer fast every few months. As with any new opKon, you may like to get a piece of paper and write down the benets on one side and the costs on the other - for you personally and no one else. Benets might be "I'll take the chance that this may benet longevity" or "I quite like the discipline of skipping a couple of meals every now and again." Costs might be "I'm worried I'll start obsessing about food again" or "I may lose a day when I fast, as I can't imagine working on an empty stomach." If the costs outweigh the benets, think twice. If the benets outweigh the costs, the nal step in the process is to see if the perceived benets can be obtained via an alternaKve route. If you like the idea that this may delay the onset of cogniKve decline (and who wouldn't) - can you do more puzzles? learn something new regularly? debate with a good 'sparring partner' who keeps you on your toes? That's just mind works outs. For physical things that you can do - remember that Alzheimer's is starKng to be called type 3 diabetes. It appears to be glucose intolerance for the brain in much

the same way that type 2 diabetes is glucose intolerance for the body. Indeed, on the day that I was wriKng the conclusion for this arKcle, the headlines worldwide were "Lose weight to beat demenKa"25 and "Obesity 'bad for brain' by hastening cogniKve decline."26 Is there any plausible mechanism by which being obese or overweight per se can cause demenKa or cogniKve decline? I can't think of one. I can, however, think of how the incessant and substanKal consumpKon of carbohydrate/ glucose, when we have not evolved to eat in this way, can cause obesity and mental harm. So, whether or not you IntermiMently Fast, for opKmal health keep sugars and things that break down into sugar substanKally curtailed, if not out of your life altogether. I hope that you've enjoyed this exploraKon of Calorie RestricKon, IntermiMent FasKng, health and weight loss. Well done Mr Mosley for ge[ng us thinking - that will keep the mind working and hopefully Alzheimer's at bay! Zo Harcombe August 2012

Copyright Zo Harcombe 2012. The Harcombe Diet PRO Plan

18 SPECIAL REPORT - Intermi3ent Fas7ng

[1] hMp:// [2] hMp://

Todd Tucker, The Great StarvaCon Experiment, published by Simon & Schuster, (2006).
[16] hMp://


[3] hMp://


v=tyQSzx0ojo [4] hMp:// things-you-should-know-about-losing- weight-27-5-09/

[5] hMp://

[17] hMp://


[18] Ancel Keys, The Biology of Human

StarvaCon, Minnesota University Press, (1950).

[19] hMp://


[6] hMp://

[20] hMp:// [21] hMp://


[7] hMp://

downloads/Farmers_Factsheet_3- Nutrients_in_foods.pdf

arKcle-2183677/Why-starvaKon-diet-actually- good--make-live-longer.html
[22] Zo Harcombe, The Obesity Epidemic: What

[8] hMp://

DietaryGuidelines/2010/PolicyDoc/ PolicyDoc.pdf (page 14) PMC2946087/

caused it? How can we stop it? Columbus Publishing (2010) Start Losing Weight: The Harcombe Diet. Columbus Publishing (2008) Primal-Blueprint.html

[9] hMp://

[23] Zo Harcombe, Stop CounCng Calories &

[10] hMp://

arKcle.cfm?id=defecKve-growth-gene-in- dwarsm
[11] hMp://

[24] hMp://

[25] hMp://

31/3/363.short 12543259 12936916 19075044

[26] hMp://

[12] hMp://


[13] hMp://

[14] hMp://

[15] hMp://


Ancel Keys, The Biology of Human StarvaCon, Minnesota University Press, (1950).

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19 SPECIAL REPORT - Intermi3ent Fas7ng

About the Author

Zo Harcombe is an author, researcher, speaker and founder of The Harcombe Diet. She has 5 books published: Why do you overeat? When all you want is to be slim; Stop CounCng Calories & Start Losing weight: The Harcombe Diet; The Harcombe Diet Recipe Book; The Obesity Epidemic. What Caused it, How can we stop it? and The Harcombe Diet for Men: No more Mr Fat guy!. All her books and further informaKon about her work are available at

About The Harcombe Diet PRO Plan

The Harcombe Diet PRO Plan is a diet and nutriKon support program for health and tness professionals to use alongside their current client acKviKes. It licences members to operate as aliates of The Harcombe Diet and to use this associaKon commercially as part of your business. Membership fees are extremely compeKKve and you will also receive weekly digests, special reports, diet & health Kps and full access to with a special members forum. Please nd more informaKon at

Copyright Zo Harcombe 2012. The Harcombe Diet PRO Plan