Thursday 25 April 2013

Lunch with Michael Mosley, the guru behind the 5:2 diet

After losing a stone and a half in five months, Xanthe Clay talks to Michael Mosley, the writer and broadcaster who popularised the hugely influential intermittent fasting diet.


 Xanthe Clay tries out her low-calorie, low-carb pan-Asian broth on Michael Mosley
Give it some stick: Xanthe tries out her low-calorie, low-carb pan-Asian broth on Michael Mosley Photo: Rii Schroer
Was this how the young David Cameron felt when he first met Thatcher? Or Stanley when he encountered Livingstone? I’m cooking lunch for Michael Mosley, the medical journalist whose Horizon programme and Telegraph article last August launched the 5:2 diet, which became a bestselling book – and changed my life.
Melodramatic, yes, but true. In the past five months on the 5:2 diet I have lost a stone and a half, reducing my Body Mass Index from a lumberingly 27 to a healthy, if admittedly hardly Kate Moss-like, 23. I still have half a stone to go, but already I can fit into clothes I bought years ago, no longer feel self-loathing about occasionally ordering cake with my coffee, and have a positively Tiggerish spring in my step.
I’m not the only one to have jumped on the 5:2 wagon. Mosley’s article on the Telegraph website has garnered nearly a million hits, and the diet book has been reprinted 13 times, selling more than 340,000 copies and e-books and topping the Amazon charts for weeks. Half my friends (including both food writers and doctors) are either on the diet or seriously considering it. Saying “I’m on a fast day” when turning down a biscuit garners sympathetic, rather than confused, looks.
Mosley himself arrives promptly for lunch. He is youthful looking for his 56 years and, encouragingly, slim but not scrawny . He is very much Mosley of the Beeb: fast, clear, incisive and also curious, as he quizzes me about my experiences on the diet – an interest I find so flattering I have to remind myself I’m the one meant to be doing the interviewing.
He makes frequent references to expert advocates of various forms of “intermittent fasting” – experts such as Dr Krista Varady in the United States and Dr Michelle Harvie in Britain, who, he is keen to point out, have done the serious scientific research, while he has merely collated the information and presented it in a way he feels is accessible.
And – crucially – he has tried it himself. Self-experimentation is a theme of much of his work. He has gone to some bizarre lengths in the name of research – swallowing a camera for the programme Inside the Human Body, which turns out to have been even more gruesome in reality than those riveting inner-space shots suggest. “The really unpleasant part was that the night before I had to drink four litres of laxative. I was meant to be going to dinner with the director general of the BBC and the gastroenterologist said, 'Not a good idea.’”
Mosley’s interest in intermittent fasting is highly personal. His father died aged 73, of complications related to type 2 diabetes, a disease inextricably linked with being overweight. “He’s been both a role model but also a sort of a threat going forward, because I see myself in him,” Mosley remarks ruefully, sipping sparkling mineral water.
So when he was diagnosed as pre-diabetic last June he tried out various intermittent fasting diets, having heard about their potential beneficial effects on insulin levels. Not that these are the only positive aspects being investigated. Harvie and Varady have focused on the cancer preventive benefits of fasting, and other researchers are looking into how it may slow Alzheimer’s. There is, however, no conclusive proof yet. “Critics reasonably say it’s early days, you need to have proper long-term trials, which is absolutely valid.”
Mosley’s life has been varied, not to say experimental. Like his father, he worked as a banker after leaving Oxford, where he had studied philosophy, politics and economics. But it didn’t appeal, and after a couple of years he enrolled in a graduate medical training scheme, intent on becoming a psychiatrist. But shortly after qualifying, he became disillusioned with “how little could really be done for people with mental illness”, and left medicine. He became a trainee producer with the BBC and spent 20 years behind the camera working on shows such as the award-winning Pompeii: The Last Day, before moving into presenting.
There was, however, one lasting benefit of his five years of medical training. “The first day at medical college the dean looked around at us – there were about a hundred of us – and said that statistically four of us would marry.” Sure enough, Mosley’s future wife, Clare Bailey, now a GP, parenting expert and founder of parentingmatters.co.uk, was among them. They now live in Buckinghamshire with their four children, aged 14 to 23.
Lunch is ready, and as it’s a fast day, I dish up shiitake mushroom, lemon grass and ginger broth, laced with low-carb Japanese shirataki noodles, one of the ingredients that have kept me on the straight and narrow over the past five months of dieting. (Holland & Barrett sell Zero brand shirataki noodles).
Mosley is delighted, or at least very polite, about being served up less than 200 calories. But will it hit the mark nutritionally? I worry about satiating hunger on fast days, and bulk up with loads of veg rather than worrying about vitamins. Mosley, however, disagrees. “I think nutritional content is absolutely key. If you are going to eat less food it should be as good as possible. You need high protein because while you store carbohydrate and fat, your body doesn’t store protein.” If it runs out of protein, it’ll break down muscle.
My loads-of-veg policy is fine, too, as it has lots of fibre – as long as I have some high-quality protein such as chicken or fish, too. I quickly add some poached chicken to our bowls. Mosley looks approving. “Fibre and protein, those are the things that fill you up. But it turns out that those are the things that are pretty good for you as well.”
At home, Mosley fasts alone. “My kids and my wife are all slim, so although supportive they don’t really do fasting days.” There are other positive benefits to having a slimmer husband, he says. “My neck went from 17 to 15½ inches, and that meant I stopped snoring. It’s to do with the visceral fat in your neck. There are times when I overindulge and my weight creeps up a bit. And she says, 'You’re snoring again!’ And I go and lose weight.”
Rather than working out BMI, Mosley recommends measuring your waist around the belly button, now considered by some health professionals to be a better indicator of a healthy weight. “Your waist measurement should be no more that half your height. Men tend to go by their trouser size, which is wrong – it’s generally smaller than your actual waist.”
To keep his svelte figure, favourite dishes on fast days include mushroom and spinach frittata and marinated steak and Asian cabbage salad, both recipes from his literary collaborator Mimi Spencer’s recipe book. He has, he says, learnt to love vegetables. “I like using the griddle for things like courgette, touches of lemon and orange juice jazz up salad leaves.”
The family have had to be on side in the battle to lose weight. “We don’t have cookies or crisps in the house. Otherwise I find 11 o’clock at night I’m looking around for a biscuit. I’ve told my wife that if she ever has any chocolate in the house she has to hide it or I will eat it. It’s completely stupid. And even as you eat it you’re thinking 'this is a really, really stupid thing to do. And I’m going to regret it 10 minutes later. And I’m still doing it.’” Mosley muses on that for a moment. “That’s what I find interesting. Such contradiction as human beings.”
After black coffee – Mosley, once a latte drinker, has taught himself to like it without milk – he has to go back to the studio. There are tweaks to be made to his new Horizon programme, on meditation and mindfulness. “I’ve had a go at the body, now I’m having a go at my brain,” he says. I’ll be watching.
The fast show
5:2 diet Choose any two days a week to stick to 500 calories for women or 600 for men
2 Day diet Restrict what you eat on two consecutive days. The rest of the week, eat a healthy Mediterranean diet
Alternate Day Fasting (ADF) Details vary but the higher number of fast days is offset by looser restrictions on non-fast days
http://www.telegraph.co.uk/foodanddrink/healthyeating/10004219/Lunch-with-Michael-Mosley-the-52-diet-guru.html
 

Wednesday 24 April 2013

5:2 diet: healthy recipes 250 calories or less

Keen to get cracking on the 5:2 diet? 500 calories a day (600 for lucky men) can seem forbidding, but Xanthe Clay’s delicious recipes with 250 calories or less will make the fast days fly by.


Xanthe Clay's slip sole with lemongrass dipping sauce has only 242 calories, ideal for those on the 5:2 diet
 
Xanthe Clay's slip sole with lemongrass dipping sauce has only 242 calories, ideal for those on the 5:2 diet Photo: CHRISTOPHER JONES
 
All recipes serve one, but can be multiplied up.
1. Scallops with pancetta and leeks
Scallops are good news for fasters, with relatively few calories but lots of flavour.
Boys’ perk: add an extra slice of pancetta
2 paper-thin 8g slices of pancetta or bacon (70 cals)
85g scallops (three medium- sized ones) (75 cals)
50g sliced, washed leeks (30 cals)
80g peas (fresh or frozen) (62 cals)
fronds from six sprigs of dill (1 cal)
30g wild rocket leaves (9 cals)
Total: 247 calories
Cut the pancetta slices in half and cook in a non-stick frying pan over a medium-high heat until the fat runs and the pancetta browns and crisps. Scoop out on to a plate and keep to one side.
Cut each scallop into two discs and pat dry on kitchen paper. Cook in the pan with the pancetta fat for a couple of minutes on each side, until browned. Lift them on to the pancetta plate.
Add the leeks to the pan and cook in the last of the scallop and pancetta juices until soft. Add the peas and cook, stirring, until the peas are hot through. Stir in most of the dill, then taste and season with salt and pepper.
Put the rocket in the middle of a plate and arrange the scallops around. Mound the leeks on top of the rocket and lay the pancetta pieces on top. Scatter with a few fronds of dill and eat straight away.

2. Green beans, spring onions and chicken liver with a soy dressing
Even liver-haters have been known to enjoy this, a tiny amount enriching the salad of beans rather than overwhelming it. It’s a huge amount of beans (I’m assuming you will be famished) but you could halve the quantity and double the liver if you are an offal fan.
Boys’ perk: a slice of pancetta, cooked as in the scallops recipe, or 40g more liver.

Ingredients
300g green beans (75 cals)
50g chicken liver (that’s about 1 whole liver) (58 cals)
¼ tsp olive oil (10 cals)
4 thin spring onions, thinly sliced (40g) (13 cals)
Dressing:
1 tbsp soy sauce (10 cals)
1 tsp olive oil (40 cals)
¼ tsp wine or cider vinegar
(0 cals)
a few drops of chilli sauce (optional)
Total: 206 calories
Steam the green beans until just done then cool under the tap.
Check the liver for any white membranes or greenish spots and cut them out.
Preheat the grill. Run the liver over with the ¼ tsp olive oil. Spread out the lobes of the liver and grill it for about two minutes on each side until lightly browned. Leave to cool.
Mix the dressing ingredients. Toss the beans and spring onion in the dressing.
Thinly slice the liver (a ceramic knife is the best implement) and mix through the salad.

3. Griddled courgettes with feta, lemon, mint, puy lentils
Puy lentils make this salad satisfyingly filling, while the flavours come from the smoky grilled courgettes, fragrant lemon zest and mint, and salt-sour feta. 1 tbsp raw lentils will be enough, if you are cooking your own, or use a tin. Keep the rest for a non-fast day, to eat mixed with chopped herbs and olive oil with meat or fish, or freeze them.
Boys’ perk: extra 20g feta cheese.
ingredients
500g courgettes, the smallest you can find (90 cals)
30g feta cheese (83 cals)
15 mint leaves (1 cal)
1 tsp olive oil (40 cals)
30g (2 rounded tbsp) cooked puy lentils (35 cals)
lemon zest (1 cal)
Total 250 cals
Cut the courgettes into long, ½ cm wide slices. Mix with the oil and a pinch of salt.
Heat a ridged griddle until smoking, then cook the courgette slices, turning once, until striped with dark brown on both sides. You will probably have to do this in at least two batches.
Transfer the courgettes to a bowl and mix with the lemon zest, feta and lentils. Just before serving, mix through the ripped mint leaves. If the feta is more salty than sharp, you may want to squeeze over a little lemon juice.

4. Roasted shallot, aubergine and cumin filo tart
Boys’ perk: use two sheets of filo, one on top of the other
Ingredients
200g small shallots (not the large “banana” shallots) (40 cals)
1 tsp olive oil (40 cals)
1 tsp cumin seed (1 cal)
a 300g aubergine (45 cals)
200g baby plum tomatoes (34 cals)
a small clove of garlic, crushed (3 cals)
½ tsp fresh thyme leaves (0 cals)
1 sheet of filo pastry (49 cals) plus ½ tsp olive oil (20 cals)
1 tbsp Greek yogurt (17 cals)
3-4 basil leaves (1 cal)
Total 250 calories
Preheat the oven to 200C/400F/Gas 6.
Cut the shallots into quarters and peel off the papery skin. Put them in a large roasting tin lined with non-stick parchment and toss in the 1 tsp olive oil and most of the cumin (keep a pinch back for the pastry). Cut the aubergine into olive-sized chunks and mix them in.
Put the roasting tin in the oven and cook for 15 minutes. Meanwhile, halve the tomatoes.
Mix the tomatoes, garlic and thyme in with the shallots and aubergines and cook for another 15 minutes.
Lay the sheet of pastry on a baking sheet lined with non-stick parchment. Brush with ½ tsp oil and sprinkle with the last of the cumin seed. Crumple up the edges lightly to make a nest about the size of a side plate. Bake for about 4 minutes, until golden and crisp.
Pile the shallot and aubergine mixture into the nest. Mix the yogurt with 1-2 tbsp water to make a pouring consistency. Drizzle over the tart and top with basil leaves.

5. Ramen soup
A big bowl of noodle soup is a great way to settle a hungry stomach.
Boys’ perk: the meat from a small, skinless cooked chicken thigh (35g or so) shredded.
Ingredients
1 sheet (60g) Ramen or Chinese egg noodles (108 cals)
½ tsp sesame seeds (8 cals)
1 sachet of miso soup (27 cals)
1 tsp mirin (7 cals)
1 tbsp Japanese soy sauce (10 cals)
½ tsp grated root ginger (1 cal)
50g spring cabbage thinly sliced (12 cals)
50g beansprouts (14 cals)
50g carrot (15 cals)
50g shiitake mushrooms, sliced (20 cals)
Total: 222 cals
Cook the noodles according to the instructions on the packet, put them in a sieve and cool under the tap.
Toast the sesame seeds in a hot dry frying pan until golden. Squeeze the gunky contents of the miso soup sachet into a saucepan with 500ml boiling water. Add the soy sauce, mirin and ginger and bring to the boil.
Meanwhile, shave the carrot into long ribbons with a potato peeler.
Add the cabbage to the soup pan and simmer for a minute. Add the carrot and mushrooms and simmer for another minute. Stir in the beansprouts.
Drain the noodles and put them in the bottom of a large soup bowl. Pour over the contents of the pan. Sprinkle with the sesame seeds and serve.

6. Spiced tomato dal
A huge, filling bowl of soup, with red lentils for heft. I’d be tempted to add a shake of smoked paprika at the end, although it’s not in keeping with the Indian spicing.
Boys’ perk: a poppadom (37 cals).
Ingredients
½ tsp vegetable oil (20 cals)
80g red onion, thinly sliced (28 cals)
¼ tsp turmeric powder (0 cals)
½ tsp black mustard seeds (optional) (0 cals)
½ tsp ground cumin seeds (0 cals)
a pinch of dried chilli flakes (optional) (0 cals)
1 clove garlic, chopped (5 cals)
500g tomatoes, chopped (105 cals)
20g red lentils (72 cals)
3 tbsp coriander leaves, chopped (1 cal)
1 tbsp Greek yogurt (17 cals)
Total: 248 cals
Heat the oil in a saucepan, add the onion and cook until soft and lightly browned.
Stir in the turmeric, cumin, mustard seed and chilli flakes (if you are using them) and cook gently for another minute.
Add the garlic, tomatoes and lentils. Stir in 500ml water and a fat pinch of salt. Simmer for about half an hour, topping up with water if necessary, until the lentils are swollen and collapsing.
Taste and adjust the seasoning. Mix the yogurt with 1-2 tbsp water to make a pouring consistency. Eat the soup scattered with coriander and drizzled with yogurt.

7. Slip sole with lemongrass dipping sauce
You could make this dish using a white fish fillet weighing about 150g. But I find fiddly food useful when dieting, forcing me to slow down and take smaller mouthfuls.
Boys’ perk: 50g cooked rice noodles mixed with the broccoli and sesame oil.
Ingredients
1 small lemon sole (about 275g) or slip sole, gutted (150 cals)
100g broccoli (35 cals)
1 tsp sesame oil (40 cals)
Dipping sauce:
1 tbsp Thai fish sauce (5 cals)
1 tbsp lime juice (2 cals)
½ tsp brown sugar (8 cals)
½ stem of lemongrass (0 cals)
½ red chilli, sliced (optional)
½ small clove garlic, chopped (2 cals)
Total: 242 cals
Preheat the grill. Sprinkle the fish with salt and put it on a piece of non-stick paper and grill for
3-4 minutes on each side, until it is just done and patched with brown.
Break the broccoli into florets and steam until just done. Toss in the sesame oil and a pinch of salt.
Strip the tough outer layers from the lemongrass and chop the tender inside finely. Mix with the rest of the dipping sauce ingredients and add 1 tbsp water (this can be done up to a week ahead and kept in the fridge). Pour into a tiny bowl and dip the fish and broccoli in it as you eat.
Calorie counts from product packaging
http://www.telegraph.co.uk/foodanddrink/9483381/52-diet-healthy-recipes-250-calories-or-less.html

Tuesday 23 April 2013

Food for thought: Fasting on alternate days could help you live longer

We’ve known for more than 70 years that calorie restriction in animals prolongs life, by as much as 40%




Getty


Want to live to a ripe old age? Or just long enough to see your favourite grandchild get married?
Well, you can vastly increase your chances with something simple and cheap with no calorie counting, diet drinks or shakes, and nothing to buy.
Stop eating two days a week. Well, virtually. Most days you can have 500-600 calories.
Oh, and I forgot to say slashing your calorie consumption twice a week will make the pounds melt away.
Recently I met up with a male friend I hadn’t seen for nine months. I didn’t recognise him. He’d lost four stone, that’s 56 pounds.
He confessed that he was doing the hardcore version of calorie restriction, which he called Alternate Day Fasting, so he was eating little on three days out of seven.
For him, this meant going all day only consuming drinks, mainly water, then a 500-calorie meal in the evening.
If you want to know what 500 calories looks like, it’s an egg or a small, thin slice of chicken, a couple of satsumas or half an apple, three oatcakes or 30g of bran flakes, a carrot or six almonds.
But cheer up! There’s always the eat-anything-you-like day to follow.
We’ve known for more than 70 years that calorie restriction in animals prolongs life, by as much as 40%.
Another big payoff is that ­fasting slashes your risk of heart disease, diabetes, stroke and cancer.
In one study at the Genesis Prevention Centre in Manchester, researchers found women on 600 calories a day, mostly milk, fruit and veg, for two days a week, lowered their breast cancer risk by 40%.
So why is AF effective? In simple terms it gives the body a rest, a chance to clean itself up, so to speak, to attend to housekeeping.
A body that is having to deal with three or four meals a day accumulates a lot of rubbish and ageing gene mutations, which lead to disease. It has no spare capacity for repairs and maintenance.
Giving your body some downtime from food frees it up to check your DNA, repair disease-producing faults, and spring-clean your cells.
This is called autophagy and is ­particularly good for your brain. Cleaned up brain cells function better, resist cognitive decline and protect themselves against stroke.
If AF seems a step too far, there’s always the kinder version of fasting for just two days a week.
Food for thought. If you’re pregnant or in doubt about ­cutting calories, see your doctor.

http://www.mirror.co.uk/lifestyle/health/miriam-stoppard-on-alternate-day-fasting-1534408

Tuesday 16 April 2013

Almost Flourless Orange Cake




Almost Flourless Orange Cake with Marmalade
by Jane Green
(recipe from The Love Verb)




Almost Flourless Orange Cake
1 orange
3 eggs
1 cup caster sugar
¼ cup plain flour, sifted
1 teaspoon baking powder
1 cup ground almonds
½ cup marmalade
icing sugar for dusting
Optional: small carton of whipping cream, rind of 1 orange

Preheat the oven to 350°F. Grease an 8" springform cake tin and line it with greaseproof paper.

Put the orange in a pan, cover with water and simmer for an hour (or nuke in a microwave for around 25 minutes) until soft. Cut the orange in half, remove pips and puree in a food processor.

Beat the eggs and sugar until pale and thick. Fold in the flour, baking powder, almonds and orange puree. Pour into the tin and bake for an hour.

Melt the marmalade in a small pan then pour through a fine sieve, pressing to get all the juice out. Spread the rind-free juice over the cake.

When cool sift icing sugar over the cake. Mix whipped cream with the orange rind and serve alongside.

I loved this cake. I would call it a dessert cake, if you know what I mean? It was moist and soft and a real treat when served with a dollop of orange scented cream. I was lucky enough to have some homemade Grapefruit Marmalade courtesy of my friend Trudi's husband and a very fine marmalade is was (thank you muchly Donald). I didn't bother sieving the marmalade as I wanted the bits of rind in the glaze and it worked very well. I just wish I had taken a photo of a slice of the cake so I could show you the lovely soft yellow crumb.

Thursday 11 April 2013

Nutritional Health


Alternate Day Fasting

Everyone’s talking about alternate day fastingAlternate Day Fasting
As Nutritional Therapist`s we don’t recommend `fad` diets, but it is always interesting to hear about the latest ones.    Cabbage soup diet, apple cider vinegar diet, Atkins diet, Dukan diet, to name but a few, and they all continuously fall in and out of favour, many don’t work and some may even be detrimental to health.  The alternate day fasting diet has been mentioned a great deal in the media, and recently Horizon aired a programme presented by Dr Michael Mossley on the subject.
If you haven’t heard the idea behind the alternate day fasting (ADF) which is also known as intermittent fasting (IF) is you eat normally one day, and the following day you restrict your calorie intake to 500 for a woman and 600 for a man.   Not only has this been shown to cause a gradual and sustained weight -loss but there are other health benefits too.  Research suggests that restricting calories is one of the few things that has been shown to increase life expectancy, it also has anti-ageing benefits, and may reduce the risk of heart disease, which is still the UKs biggest killer.  The research into this subject is still ongoing, but its all looking very promising.
So it seems ADF is not another `fad` diet, and there is a slightly easier version for those who are not tempted by fasting every other day.  The 5:2 version allows you to eat normally for 5 days and fast on 2 non-consecutive days.
Jenny Burn Nutritional TherapistWatch this space, as some of the Therapists on the Nutrition Mission team are going to be testing the 5:2 version over the coming weeks and we will be updating you with the results.  If you are planning on testing out fasting too, keep an eye out for our delicious specially designed recipes that you will be able to follow on your fasting days too

Jenn





http://blog.nutritionmission.co.uk/2013/02/21/alternate-day-fasting/

y Burn BSc N.Med mBANT CNHC Registered

Wednesday 10 April 2013

Buffered Alternate Day Fasting & Exercise


Buffered Alternate Day Fasting + Light Aerobics Cut Body Fat, Maintain Lean Mass & Improve LDL Particle Size. Plus: Conventional Alternate Day Fasting Detrimental for Fertility

This is how the "buffered" alternate day fast works: You eat 1/4 of the White Choc Banana Cream Pie on your fasting day and a whole pie on the next one - well, not really, but the ratios would be right ;-)
I guess at least the SuppVersity facebook friends are probably going to remember the study today's article is dealing with: "Alternate day fasting and endurance exercise combine to reduce body weight and favorably alter plasma lipids in obese humans." To me that sounded like Intermittent Fasting Done Wrong Does Still Produce Great Results, When You Combine It With an Aerobic Exercise Regimen", when I first read the abstract. After taking a brief look at the full-text (thx John!),  however, my perspective on the study changed from "even a dog has its day" to "that oes look interesting, let's see whether this kind of buffered alternate day fasting" is able to take bear up with a classic intermittent fast. 


A brief warning with respect to the data in figure 1: I know that a couple of you are too lazy to actually read the article and do headline + figure hopping. If you intend to to that, please keep in mind that the data in figure 1 is from another recent study, I used to illustrate the negative effects of "real" alternate day fasting.

Not all alternate day fasting is created equal 

For the course of this 12-week, randomized, controlled, parallel-arm feeding trial the participants, 61 women and only 3 men aged 25 to 65 years, overweight / obese (BMI 30-39.9kg/m²) and weight stable for at least 3 months were randomized to one of the four study arms (unfortunately the data does not allow for any conclusions, whether the men and women reacted differently to the intervention or "real" alternate day fasting the data from the rodent study I discuss in the interlude surrounding figure 1shows that this is the case, though):
  • control group (C): sedentary, no diet
  • exercise group (E): 25, 30, 35, 40min at intensities of 60, 65, 70, 56% of the calculated HRmax (intensity and duration were increased in week 4, 7 and 10)
  • alternate day fasting group (ADF): after 4-week controlled feeding period the study concluded with an 8-week self-selected feeding period.
    As long as study subjects just have to eat what scientists serve them, every diet works. When they are however told to eat a high protein diet, for example, even the reported nutrient intake diverges massively from what the scientists had in mind, when they devised the protocol - you don't believe me? Well, then read for yourself, "What Really Happens, When Science Meets the Real World"
    "During the controlled feeding period (week 1-4) participants consumed 25% of their baseline energy needs on the "fast day” (24 h) and consumed food ad libitum on each "feed day” (24 h). [...] The diet consisted of a 3-day rotating menu plan, and all fast day meals were prepared in the metabolic kitchen of the Human Nutrition Research Unit (HNRU). Fast day meals were consumed between 12.00 pm and 2.00 pm to ensure that each subject was undergoing the same duration of fasting.[...] During the self-selected feeding period (week 8-12) subjects continued with the ADF regimen but no the fast day food was provided to them. Instead, each subject met with a dietician at the beginning of each week to learn how to maintain the ADF regimen on his or her own at home." (Bhuatin. 2013)
    During the counseling sessions the participants were also instructed to make (I quote) "healthy foodchoices on the ad libitum feed days by choosing low fat meat and dairy options and
    increasing fruit and vegetable intake." (Bhutani. 2013)
  • combination group (ADF + E): combination of alternate day fasting and exercise protocol

Table 1: Nutrient composition of the fast day diet provided to the combination and ADF groups (Bhutani. 2013)
So, as you've learned from the above overview this was no "alternate day fast", as I had expected it to be, when I read the term "Alternate Day Fasting (ADF)" in the abstract of the study. With 450kcal/day and a nutrient composition providing 50% of the energy in form of carbohydrates, and 25% (each) from fat and protein the "fasting days" were characterized by a low caloric intake (see table 1), but should not have triggered a similar starvation response as the classic alternate day fasting regimen in a recently published rodent study by Kamur et al. from which the data in figure 1 is derived.

Let's briefly take a look why "real" alternate day fasting may not be a good idea

As you can see the effect of the alternate day fasting regimen in the Kumar study, in the course of which the rodents simply did not receive any food for a whole day, had profound negative effects on the hypothalamo-gypophysial-gonadal axis - especially in the female rodents.
Figure 1: Effects of every-other day fasting vs.ad libitum feeding on ovarian weight, estradiol, lutenizing hormone, leptin, and testosterone in female and male rodents (Kumar. 2013)
Now the first thing that will jump your eye is certainly the profound increase in serum estrogen in the IF group. Looks strange and certainly not anywhere near what you would have expected right? If you think that this cannot be that bad, you are probably a man, is that right? I see... so what really is bad about the estrogen explosion is actually that it is "living proof" of the total disruption of the cyclic interplay between estrogen and progesterone that's at the heart of female (in-)fertility (on a side note: the male rodents simply got skinny fat on that regimen).

Now why didn't these adverse events occur in the study at hand? 

Actually I am only assuming that there were not similar negative effects in the study at hand. After all, we don't have the respective hormonal and even in the rodents it took it's time (2 cycles) until the females were totally infertile. Changes like these would thus probably have gone unrecognized. I do however suspect that the major factors contributing to the overall hormonal decline in the rodent study were the extendended time-span without food and the overall caloric deficit, which is usually ~30-40% of the habitual intake in rodents on alternate day fasting regimen, as they do not compensate for the fasting day on the subsequent day.
Figure 2: Changes in body composition in the combined, ADF, exercise and control groups (Bhutani. 2013)
With the extended fast being absent and a ~75% reduction in calorie intake on the fasting days, only (humans are unfortunately much better in "compensating" for a lack of food on a fasting day, anyway ;-)and the huge amount of adipose tissue the rodents in the Kumar study obviously did not have as an "emergency reserve", it is therefore unlikely that the beneficial changes in body composition Bhutani and his colleagues observed in their 64 subjects (see figure 2) were accompanied by hormonal deteriorations (although 61 of them were, as previously mentioned, female).
Figure 3: Changes in lipid profile (left) and glucose metabolism in the combined, ADF, exercise and control groups (Bhutani. 2013)
It is nevertheless interesting to see that there were no significant improvements in fasting glucose, insulin or HOMA-IR (the measure of long-term blood glucose levels; not shown in figure 3) in any of the groups. Moreover, the improvements in total LDL and HDL cholesterol were only significant in the combined group and that the total amount of the inflammatory marker CRP remained essentially the same in all four arms of the 12-week intervention study.

Image 2: Ramadan fasting can serve as a relatively well studied "model" of intermittent fasting. With the additional restriction of water intake and the common practice of rising early to have breakfast there are yet non-negligible differences. You can find more information about the strengths and limitations of this model in Part 2 andPart 3 of the IF series.
A brief reminder for everyone who missed theIntermittent Thoughts on Intermittent fasting series back in the day: If there is one thing we can take away from studies investigating the effects Ramadan fasting (a Muslim fasting ritual, where you eat only when the sun goes down) it is that eating the same amount of food at different times of the day alone is not going to make you lose weight. If you do intermittent fasting in order to lose weight you still have to achieve a caloric deficit. Plus, when you are doing it during a bulk, I personally suspect that you are more likely to gain body fat, simply because your body cannot make "good use" (=muscle glycogen and skeletal muscle protein) from all the food you will be cramming down in a small fasting window. So, if you insist on IF on a bulk, do at least increase your feeding window to 8h to be able to spread your energy intake more evenly.
Based on a comparison of the data from all three groups, we can yet also conclude that it is the alternate day fasting (or probably rather the caloric deficit) that exerts the beneficial effects on what the scientists subsume under the umbrella term "CHD risk indicators":
"the combinationof ADF plus exercise decreased LDL cholesterol (12% from baseline) while increasing HDL cholesterol (18% from baseline); a change that was not noted for any other intervention. The combination group also experienced an increase in LDL particle size, and a  reduction in the proportion of small LDL and HDL particles." (Bhutani. 2013)
Only later in the discussion of their results do they mention that those "CHD risk indicators" improved to the same extend in the ADF only group - with even more significant changes in the particle profile.



Learn why breakfast is probably not the "most", but rather the least "important meal of the day" (read more).
Bottom line: The weight and fat loss are certainly intriguing. The regimen appears to be reasonably easy to follow and the fact that the improvements in glucose metabolism were marginal could well be related to the fact that the subjects were - despite being seriously overweight (!) - not diabetic.

Keeping all that in mind I am still not convinced that a regular intermittent fasting routine (16-18h fasting window on every day; learn more about intermittent fasting here at theSuppVersity) and a combined aerobic + strength training regimen would not have yielded even superior results. The average physical culturist probably will be better of with this by now almost "classic" diet routine. 

References:
  • Bhutani S, Klempel MC, Kroeger CM, Trepanowski JF, Varady KA. Alternate day fasting and endurance exercise combine to reduce body weight and favorably alter plasma lipids in obese humans. Obesity (Silver Spring). 2013 Feb 14.
  • Kumar S, Kaur G. Intermittent Fasting Dietary Restriction Regimen Negatively Influences Reproduction in Young Rats: A Study of Hypothalamo-Hypophysial-Gonadal Axis. PLoS ONE. 2013; 8(1): e52416. 
http://suppversity.blogspot.co.uk/2013/02/buffered-alternate-day-fasting-light.html

Tuesday 9 April 2013

Alternate-day fasting and chronic disease prevention: a review of human and animal trials1,2,3


  1. Marc K Hellerstein
+Author Affiliations
  1. 1From the Department of Nutritional Sciences and Toxicology, University of California at Berkeley, Berkeley, CA

Abstract

Calorie restriction (CR) and alternate-day fasting (ADF) represent 2 different forms of dietary restriction. Although the effects of CR on chronic disease prevention were reviewed previously, the effects of ADF on chronic disease risk have yet to be summarized. Accordingly, we review here animal and human evidence concerning ADF and the risk of certain chronic diseases, such as type 2 diabetes, cardiovascular disease, and cancer. We also compare the magnitude of risk reduction resulting from ADF with that resulting from CR. In terms of diabetes risk, animal studies of ADF find lower diabetes incidence and lower fasting glucose and insulin concentrations, effects that are comparable to those of CR. Human trials to date have reported greater insulin-mediated glucose uptake but no effect on fasting glucose or insulin concentrations. In terms of cardiovascular disease risk, animal ADF data show lower total cholesterol and triacylglycerol concentrations, a lower heart rate, improved cardiac response to myocardial infarction, and lower blood pressure. The limited human evidence suggests higher HDL-cholesterol concentrations and lower triacylglycerol concentrations but no effect on blood pressure. In terms of cancer risk, there is no human evidence to date, yet animal studies found decreases in lymphoma incidence, longer survival after tumor inoculation, and lower rates of proliferation of several cell types. The findings in animals suggest that ADF may effectively modulate several risk factors, thereby preventing chronic disease, and that ADF may modulate disease risk to an extent similar to that of CR. More research is required to establish definitively the consequences of ADF.


INTRODUCTION

Calorie restriction (CR), defined as a reduction in energy intake without malnutrition, has been shown to increase life span, improve numerous functional indexes, and reduce metabolic risk factors for chronic disease in several mammalian species (12). CR regimens have consisted of reducing food intake to 60–85% of daily energy needs. As an alternative to traditional CR, another dietary regimen, termed alternate-day fasting (ADF), has also been tested. ADF regimens generally involve a “feast day” on which food is consumed ad libitum that alternates with a “fast day” on which food is withheld or reduced. The feast and fast periods are typically 24 h each, but they may vary. A key point about the ADF approach is that overall calorie intake need not be limited; instead, the frequency of food consumption is altered (3).
The purpose of this review is to summarize the relatively sparse but highly suggestive literature on ADF regimens. Although the effects of CR on chronic disease prevention were discussed in reviews conducted in the past few years (4-6), the ability of ADF to alter chronic disease risk has not yet been summarized. In particular, the key question—whether ADF has effects on risk modulation comparable to those of CR—remains uncertain. Accordingly, our objective was to review the evidence from both animal and human trials concerning ADF and the risk of chronic diseases, such as type 2diabetes mellitus, cardiovascular disease (CVD), and cancer. In addition, when possible, the magnitude of risk reduction due to ADF will be compared with that due to CR.

BENEFITS OF CALORIE RESTRICTION REGIMENS

A large body of evidence for the physiologic benefits and life-extending properties of CR now exists. Restricting daily energy intake by 15–40% has been shown in both animals and humans to improve glucose tolerance and insulin action, which indicates an enhancement in insulin sensitivity (78); to reduce blood pressure and the heart rate, which is consistent with benefits for cardiovascular health (9-11); and to reduce oxidative damage to lipids, protein, and DNA, which implies a protective effect against oxidative stress (12-15). Many other effects of CR have been documented, including increased average and maximal life span (12), reduced incidence of spontaneous and induced cancers (13), resistance of neurons to degeneration (14), lower rates of kidney disease (15), and prolongation of reproductive function (16).
Although the precise mechanisms responsible for such effects are still not clear, several general hypotheses have been proposed—most prominent are the stress resistance hypothesis, the oxidative stress hypothesis, and the induction of a scarcity program hypothesis (317-19). The first hypothesis suggests that, after prolonged dietary restriction, increased resistance to different types of stressors occurs, which permits the cells of many tissues to resist injury induced by genotoxic, metabolic, or oxidative insults (20-22). The second hypothesis proposes more specifically that fewer free radicals are produced in the mitochondria of cells, because dietary restriction generally limits energy utilization, which results in less cellular oxidative damage (3). The third hypothesis proposes that CR induces intrinsic cellular and organismal programs for adaptation to scarcity, which result in the slowing of metabolic processes such as cell proliferation that contribute to senescence; this hypothesis has been strengthened by findings in yeast (19). The effects of ADF on these proposed mechanisms have not been explored as extensively as have the effects of CR, but some evidence has been generated, and that will be reviewed here.

EFFECT OF ALTERNATE-DAY FASTING ON TYPE 2 DIABETES RISK

Animal studies

To date, 12 studies using animal models have examined the effect of ADF on chronic disease risk (23-34Table 1). Approximately half of these studies examined variables related to diabetes, such as fasting glucose and insulin concentrations, fat oxidation, degree of insulitis, and occurrence of type 2 diabetes. Fasting glucose concentrations have generally been reported to decrease in response to ADF in animal models. Three studies found reduced circulating glucose concentrations after a 20–24-wk intervention (2730), whereas one study reported no effect on glucose concentrations after a 16-wk treatment (24). In the trials that measured insulin concentrations, consistent reductions were noted after ADF regimens that lasted 20 (27) and 24 (28) wk. It is interesting that, in the study of Anson et al (27), both glucose and insulin concentrations decreased to a similar extent in the ADF and the 40% CR groups. Increases in fat oxidation in liver and muscle have also been observed after relatively short periods (8 wk) of ADF (33).
View this table:
TABLE 1
Animal trials examining the effect of alternate-day fasting (ADF) on chronic disease risk factors1
Because impaired fat oxidation may contribute to ectopic accumulation of intracellular lipid and the development of insulin resistance (35), these increases in fat oxidation may increase insulin sensitivity. Also noted by Anson et al was a doubling of the plasma concentrations of β-hydroxybutyrate in the ADF group but no change in the control group. In contrast, concentrations of this metabolite decreased in the 40% CR group but not in the control group (27). These results suggest that high rates of fatty acid oxidation leading to ketogenesis occurred with ADF but not with 40% CR. Moreover, reduced occurrence of insulin-dependent diabetes in response to ADF has been reported by Pedersen et al (30). These authors found that 77% of the BB rats fed ad libitum control diets developed diabetes, whereas only 52% of the animals fasted for 24 h on alternate days became diabetic. The degree of insulitis, however, was not affected, which suggested that the mechanism most likely did not involve modulation of this inflammatory variable (30).

Human trials

Risk factors for type 2 diabetes were measured in each of the 3 published human studies of ADF (36-38Table 2). Evidence from these trials suggests that ADF does not alter fasting concentrations of glucose but may beneficially modulate other indexes of diabetes risk, such as insulin sensitivity. Specifically, Halberg et al (38) observed that, when normal-weight persons fasted for 20-h periods (fast day) and then ate their habitual diet ad libitum on alternate days (feast day), the insulin-mediated glucose uptake increased after 2 wk of intervention, as measured by using the euglycemic-hyperinsulinemic clamp technique. These results are supported by a study conducted by Heilbronn et al (36), which found that, after 3 wk of ADF, insulin response to a test meal was reduced, which implied improved insulin sensitivity. It is interesting that this effect on insulin sensitivity occurred only in male subjects (36).
View this table:
TABLE 2
Human trials examining the effect of alternate-day fasting (ADF) on chronic disease risk factors1
Another diabetes risk factor that has shown a sex-specific effect is glucose tolerance. After 3 wk of ADF, women but not men had an increase in the area under the glucose curve (36). This unfavorable effect on glucose tolerance in women, accompanied by an apparent lack of an effect on insulin sensitivity, suggests that short-term ADF may be more beneficial in men than in women in reducing type 2 diabetes risk. However, because minimal data and no longer-term studies are available to support this important hypothesis, more studies are needed. The effect of ADF regimens on insulin concentrations appears equivocal (3738). Specifically, Halberg et al (38) found that 2 wk of ADF had no effect on fasting insulin concentrations, whereas Heilbronn et al (37) found that 3 wk of this intervention decreased insulin concentrations, but only after a 32-h fast. Further research examining the time course of ADF effects on such diabetes-related variables could help clarify this matter. Also examined was the responsiveness of skeletal muscle and adipose tissue to ADF (38). A 2-wk ADF regimen had no effect on intramuscular triacylglycerol (IMTG) concentrations in normal-weight men (38). In adipose tissue, an inhibitory effect of insulin on adipose tissue lipolysis was observed after 2 wk of intervention (38). Because increased concentrations of free fatty acids have been implicated in the pathogenesis of type 2 diabetes (39), this decrease in lipolysis and circulating concentrations of free fatty acids may represent an indirect protective effect of ADF on diabetes risk.

EFFECT OF ALTERNATE-DAY FASTING ON CARDIOVASCULAR DISEASE RISK

Animal studies

As a means of assessing cardiovascular response to ADF, trials in this area have examined heart rate, blood pressure, circulating lipids, and ischemic injury. In a recent study by Mager et al (24), reductions in heart rate were observed in Sprague-Dawley rats after 16 wk of ADF. Similar effects on heart rate were also found by Wan et al (28) after 24 wk of ADF. In both of these trials, treatment-induced decreases in systolic and diastolic blood pressure were noted after 4 wk, and the lower blood pressures persisted throughout the course of the studies. Moreover, the magnitude of the effect on heart rate and blood pressure was similar in the ADF group and a 40% CR group, which suggests that ADF may be as beneficial as CR in modulating these variables (24).
In addition, Krizova and Simek (32) observed decreases in circulating lipid concentrations, and, after 8 wk of ADF, both total cholesterol and triacylglycerol concentrations decreased in adult mice. Moreover, the cardiac myocyte response to myocardial infarction (MI) induction has been studied by Ahmet et al (25). MI was induced by coronary artery ligation after 12 wk of ADF or control ad libitum diet in Sprague-Dawley rats. At 24 h after MI induction, the number of apoptotic myocytes in the affected area was one-fourth that in the ad libitum–fed controls, and the size of the MI in the ADF goup was half that in the ad libitum–fed controls. Also noted was a distinct reduction in neutrophil infiltration, which suggested a decrease in inflammatory response (25).

Human trials

Heilbron et al (37) examined the effect of ADF on CVD risk. When human subjects fasted on alternate days for a short period (3 wk), circulating concentrations of HDL cholesterol increased, whereas triacylglycerol concentrations decreased (37). It ispossible that these effects resulted from the decreases in body weight (2.5%) and fat mass (4.0%) observed in these subjects, who were unable to consume sufficient calories on the feast day to maintain an isocaloric state (37). It is interesting that the shifts in lipid concentrations were shown to be sex specific: ie, only the women had an increase in HDL-cholesterol concentrations, and only the men had a decrease in triacylglycerol concentrations (37). There is no clear explanation for these sex-based differences. The effect of ADF on blood pressure was also examined in this study. After 3 wk of intervention, neither systolic nor diastolic blood pressured changed in either the male or female subjects (37). This study included only normotensive persons, however. It will be of interest in future studies to examine the effect of this dietary regimen on blood pressure in other patient groups, such as those who are hypertensive, overweight, obese, and hyperlipidemic.

EFFECT OF ALTERNATE-DAY FASTING ON CANCER RISK: ANIMAL TRIALS

The protective effect of ADF on cancer survival was first described by Seigel et al (34). In this study, 3–4-mo-old rats were administered an ADF regimen beginning 1 wk before inoculation with MAT 13762 acsites tumor cells (34). Twelve of the 24 rats (50%) in the diet-restricted group survived 10 d after tumor inoculation, in comparison with only 3 of 24 animals (12.5%) in the control group, which had been fed ad libitum (34). The response to ADF of certain biomarkers of cancer risk, ie, insulin-like growth factor-1 (IGF-1), has also been investigated (2728), but the results have been inconsistent. Whereas Anson et al (27) reported increases in IGF-1 in response to 20 wk of ADF, Wan et al (28) reported a clear decrease after 24 wk of treatment. IGF-1 is a potent promoter of cell proliferation and has been shown to decrease in response to CR (40). The animals in the study of Anson et al (27) did not lose any weight, whereas animals in the study of Wan et al (28) did lose weight; the lack of overall net negative energy balance may explain the different IGF-1 responses in those studies.
More recently, the protective effect of the ADF restriction protocol on age-associated lymphoma and hepatocarcinogenesis was examined in mice (26). After 16 wk, the incidence of lymphoma in OF1 mice administered an ADF regimen was 0% and that in the control group was 33%. Because the ADF group mice consumed roughly the same total amount of food as the control mice, the efficacy of ADF was independent of total calorie intake (26). Also noted in that study was a significant, treatment-induced increase in spleen mitochondrial superoxide dismutase (SOD) activity, which was associated with reduced mitochondrial generation of reactive oxygen species (ROS). The effect of ADF on hepatocarcinogenesis has also been examined (29) after 4 wk of ad libitum feeding. In that study, Wistar rats were injected with diethylnitrosamine to initiate liver carcinogenesis and then fed on alternate days for 48 wk. When compared with ad libitum feeding, ADF inhibited the development of preneoplastic lesions and also decreased the number and size of liver nodules (29). These findings strongly support the hypothesis that long-term ADF may exert an antipromotional effect on experimental carcinogenesis, as has been shown in many studies of CR. Moreover, strong physiologic evidence in favor of the antipromotional effects of ADF was recently reported by Hsieh et al (23). After 12 wk of treatment, reduced rates of proliferation of several cell types, including mammary epithelial cells, skin epithelial cells (keratinocytes), and splenic T-cells, was observed (23). These changes induced by ADF were similar to, though not quite as potent as, those seen in the CR groups.
ADF regimens have also been shown to increase mean and maximal life span in certain strains of mice (31). When ADF regimens were initiated in C57BL/6J mice at ages 2, 6, and 10 mo, body weight decreased and maximal life span was extended (31). It is interesting that, when the same ADF protocol was administered to A/J mice, body weight was not affected, and life span was increased only in the group that began ADF at age 2 mo (31). These findings suggest that ADF-induced changes in body weight and maximal life span may be strongly influenced by genotype and the age at which ADF is initiated.

EFFECT OF ALTERNATE-DAY FASTING ON OTHER METABOLIC VARIABLES: HUMAN TRIALS

The effect of short-term ADF regimens on other metabolic variables, such as body temperature, resting metabolic rate (RMR), and various hormone and cytokine concentrations, has also been examined in human subjects (3637). In the study by Heilbronn et al (37), neither body temperature nor RMR was affected by 3 wk of treatment. On the other hand, overall fat oxidation was shown to increase by an average of 15 g/d over the course of the trial, according to indirect calorimetry. The authors also observed a positive correlation between fat oxidation and weight loss, which suggested that those subjects with a greater ability to oxidize fat may have lost more weight (37). Thus, whether the weight loss noted is a result of ADF may depend on a person's ability to oxidize fat. Heilbronn et al (36) also examined treatment-induced changes in the expression of certain skeletal muscle genes involved in fat oxidation, including β-hydroxyacyl CoA dehydrogenase, fatty acid translocase, pyruvate dehydrogenase kinase 4, carnitine palmitoyltransferase 1, and uncoupling protein 3, as well as the expression of genes implicated in mitochondrial biogenesis, including peroxisome-proliferator-activated receptor-gamma co-activator 1, nuclear respiratory factor 1, and cytochrome C. They reported that a 3-wk treatment had no effect on the expression of any of these genes. The response of circulating concentrations of certain adipokines—ie, adiponectin, leptin, interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α)—has also been examined (38). Concentrations of leptin, IL-6, and TNF-α did not change in response to ADF; in contrast, concentrations of adiponectin increased by 37% (38). Cnop et al (41) and Higashiura et al (42) both reported that circulating concentrations of adiponectin are positively correlated with insulin sensitivity, which suggests a possible role of this adipokine in the insulin-sensitizing effect noted in the present trial (38).

SUMMARY OF FINDINGS: ALTERNATE-DAY FASTING IN HUMAN AND ANIMAL TRIALS

Some discrepancies between human and animal ADF data are evident. With regard to the effect of ADF on the risk of type 2 diabetes mellitus, the results to date from human trials have been inconsistent, whereas the animal evidence suggests favorable alterations. Fasting glucose concentrations in rodents, for example, consistently were lower after 20 wk of treatment (272830), whereas, in humans, no effect was seen after 2–3 wk of ADF (3738). It may be that longer intervention periods are required to alter glucose concentrations in human subjects. In the case of fasting insulin concentrations, equivocal findings were noted in humans (3738), whereas consistent decreases have been seen in animals (2728). Moreover, animal data indicate that ADF is just as efficacious in decreasing fasting glucose and insulin concentrations as is daily CR (27). Although neither glucose nor insulin concentrations were affected in the brief human trials carried out to date, it is interesting that findings such as increased insulin-mediated glucose uptake and reduced adipose tissue lipolysis have been reported (38). In animal models, fatty acid oxidation in liver and muscle is increased with ADF (33); this may indicate that ectopic accumulation of intracellular lipid could be decreased, which in turn may lead to improved insulin sensitivity (43). Nevertheless, it should be noted that, in obese human subjects, CR does not affect intramyocellular lipid content but does result in decreased lipid accumulation in liver (44). Complementary to this evidence, the incidence of type 2 diabetes risk was lower in rodents fed on alternate days than in ad libitum–fed controls (30). In sum, the favorable effects noted in animal studies suggest that prolonged ADF is a beneficial means of lowering type 2 diabetes risk. Results from human studies, however, are less clear. It seems reasonable to expect that ADF will improve insulin sensitivity in humans, but the conflicting findings make it difficult to be certain about this. Longer intervention trials (ie, ≥20 wk) in human subjects may help to clarify this issue.
Although overall beneficial modulations in risk factors for vascular disease have been found, with respect to blood pressure, the evidence from animal studies has shown a consistent decrease in both systolic and diastolic readings (2428), whereas data from human trials have shown no effect on either variable (37). One possible explanation for this inconsistency may be the differences in the duration of intervention. Because an effect on blood pressure readings was identified only after a 4-wk treatment in animals (2428), treatment for 3 wk in the human study may not have been long enough. Alternatively, weight loss, ie, negative energy balance, may be required for a blood pressure effect in humans. In the case of circulating lipid concentrations, beneficial modulations have been noted in both human and animal studies (3237). Specifically, human data show treatment-induced increases in HDL-cholesterol concentrations and reductions in triacylglycerol concentrations (37), and results in rodents show decreases in total cholesterol and triacylglycerol concentrations (32). Also shown, although only in rodent models, were improvements in cardiac response to MI induction (25) and decreases in heart rate (2428). In addition, the decreases in heart rate and blood pressure induced by ADF were similar to those induced by CR (24). Taken together, these improvements suggest that ADF may help reduce the risk of CVD.
To date, the direct effect of ADF on cancer has been tested only in animal models. Most of those trials suggest a pronounced beneficial effect on cancer risk factors, including substantial decreases in lymphoma incidence (26), increases in spleen SOD activity accompanied by reductions in ROS generation (26), inhibition of hepatic preneoplastic lesion development (29), and a greater survival rate after tumor inoculation (34). The physiologic evidence of clear reductions in proliferation rates of several cell types—including mammary epithelial cells, keratinocytes, and splenic T-cells—induced by ADF regimens also supports the antipromotional actions of this intervention (23). The antiproliferative mechanism remains unknown, however, because the effects of ADF on IGF-1 concentrations have been inconsistent (2728). Nevertheless, most of these studies have reported a protective effect, so it is reasonable to propose that ADF will prove to be an effective means of decreasing cancer risk. Studies in human subjects are still required to answer this important question.
An interesting but unresolved issue is the effect of ADF on body weight. Body weight has been shown to be highly variable in response to ADF in both human and animal models. In some animal models, when ADF regimens have been applied in the short term, no effect on body weight has been noted after 2 wk (34), whereas gains in weight were noted in other trials after 8 wk (3233). It is possible that the animals in the 8-wk trial may have overcompensated for the lack of food on the fast day by eating more than twice their average daily intake on the feast day. In other studies, when ADF regimens were administered for 12 wk, body weight was found to decrease (2325), but, when ADF regimens were administered for 16 wk, no effect on body weight was observed (2426). Trials examining the effects of long-term (>20 wk) ADF in animals (28-31) have fairly consistently found decreases in body, although the study by Anson et al (27) did not. Such findings suggest that the animals were unable to consume twice their daily food intake on the feast day for longer periods, which resulted in a loss of body weight. There clearly is variability in the capacity of animals, even within the same strain of mouse, to compensate for a fast day on the feast day (27). A variety of factors, such as housing conditions, palatability, or energy density of diet, and genetics can be hypothesized as influencing compensation. Understanding the factors controlling compensation is an important area for future research.
The effect of ADF on body weight in humans is difficult to infer because of the very short trial durations and the small number of studies published to date. As was seen in animal trials, 2 wk of ADF had no effect on body weight in normal-weight human subjects (38). Nevertheless, when the intervention period in humans was extended to 3 wk, a decrease in body weight (≈2.5 kg) was noted (3637). This decrease in body weight may have resulted from an inability to consume an adequate amount of food on the feast day to sustain body weight. Similar findings were noted in animals, but only after much longer trial durations (>20 wk). An important study design issue is whether weight loss should be prevented in human ADF studies by “forced” maintenance of calorie intake. Forcing maintenance of intake may produce harmful effects over the long term, so this approach cannot currently be recommended. It is also possible that weight loss in humans following an ADF regimen will prove to be minor or transient. In contrast, striving for full compensation of calorie intake (ie, no weight loss) in studies lasting only weeks or a few months is unlikely to have significant adverse health consequences. The absence of weight loss would allow useful comparisons and distinctions between ADF and CR. These issues will require consideration by investigators who conduct future human trials with ADF.

CONCLUSIONS

Findings to date from both human and animal experiments indicate that 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. The effect of ADF regimens in insulin-resistant or diabetic populations also should be determined, because they could help to clarify the role of ADF as a treatment for preexisting diabetes rather than as a protection against diabetes.
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 CR in improving certain indexes of risk of type 2 diabetes and CVD, although the number of studies directly comparing the 2 regimens is small. Further analysis of the mechanisms responsible for beneficial effects of ADF is clearly warranted, particularly if these effects occur in the absence of negative energy balance. Novel mediators and therapeutic strategies may thereby be uncovered. 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 SOD activity accompanied by decreases in mitochondrial generation of 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.

http://ajcn.nutrition.org/content/86/1/7.full