The 25:5 diet - first impressions

Those who know me personally may be surprised that I'm dieting. At a bit over 6 feet tall in the old units, and about 73kg in the new, I am not what you would call overweight.

But for me,  dieting is not about weight. Since being diagnosed with MS in 2007, I've become much more interested in my health, including doing the best that I can do with diet. Diet is in our modern medical system, largely overlooked as a tool to treat illness and maintain optimal health. We tend to focus on pills and surgery for almost everything, but for MS (and for many other illnesses) neither of these approaches have been particular successful.

Research has shown that restricting dietary calories increases healthy lifespan in every animal that has been studied from nematode worms to monkeys. And that you don't need to do it all the time to have the same kinds of effects - alternate day fasting, intermittent fasting and the now popular "5:2 diet" show various health benefits. In the case of the 5:2 diet, by restricting calories on two non-consecutive days each week and eating normally on the other 5 days. Various versions of these diets are designed to get the positive effects without causing too much suffering in the dieters (this is important because if too much suffering is involved most people won't be able to follow the diet for any length of time and the whole thing becomes a bit pointless).

The diet I want to talk about today doesn't have a name yet, other than "Fasting Mimicking Diet" as labelled in the research paper that it comes from. This isn't very catchy or very informative though, so I'm going to call it the "25:5 diet", for reasons which will become clear.

First, lets look at this science. Although this isn't my area and there are doubtless things I haven't picked up on or don't understand fully, I feel I can make a pretty reasonable summary of what the findings were. The paper is "A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and Healthspan", by rather a lot of authors: Sebastian Brandhorst, In Young Choi, Min Wei,  Chia Wei Cheng, Sargis Sedrakyan, Gerardo Navarrete, Louis Dubeau, Li Peng Yap, Ryan Park, Manlio Vinciguerra, Stefano Di Biase, Hamed Mirzaei, Mario G. Mirisola, Patra Childress, Lingyun Ji, Susan Groshen, Fabio Penna, Patrizio Odetti, Laura Perin, Peter S. Conti, Yuji Ikeno, Brian K. Kennedy, Pinchas Cohen, Todd E. Morgan, Tanya B. Dorff, and Valter D. Longo; in the Cell Metabolism journal (for which free online access is given here).

These guys applied the Fasting Mimicking Diet to three very different organisms: yeast, mice, and people. Now clearly the comparison isn't exact, for instance yeast doesn't get cancer, and you can't cut up human test subjects to measure their organs, but there are a lot of points at which you can make comparisons. The basic approach is to trick the body into thinking it is starving (and in a sense, it is) over a period of 4 or 5 days by 1) restricting calories to less than half of the daily metabolic requirement and 2) restricting protein to less than a quarter of the recommended daily minimum. The results are summarised in the table below:

Impact	Yeast	Special Mice	Humans
Diet cycle	Nutrient rich growth medium for 2 days, followed by water for 2 days.	Half of normal calories on day 1, 10% of normal calories day 2-4, by low protein and low fat food. Day 5 to 14 normal rodent chow. The mice ate enough extra on the feed days to make up for the diet in calorie terms, over each cycle.	Half of normal calories on day 1, a third of normal on day 2-5, limit protein intake to 9-10% of total energy budget. Day 6 to day 30 eat whatever you like.
Lifespan	About a 20 to 50% lifespan extension, depending on how you look at it.	Half of the control group had died by 25.5 months. In dieting mice, this point didn't occur until 28.3 months, an 11% life extension. The life extension effect got larger the older the mice got (the control mice died sooner) but there was no effect on maximum age achieved.	Can't assess that in a short clinical trial. None of the subjects died during the study.
Cancer	Yeast don't get cancer, It's a multi-cellular organism's problem.	The special mice are a strain that gets cancer a lot. Without doing anything mean to them, about 67% of the control mice have some type of cancer at the end of their life. In the dieting mice, the rate was 40%.	No one got cancer during the study (and no one was expected to).
Visceral fat (the stuff that sits in your abdominal cavity, around your vital organs)	Yeast don't have visceral fat	Compared to the control mice, the dieting mice had the same lean body mass as the controls, but less total body fat (and less weight). Fat under the skin was about the same, but visceral fat was lower in the dieting mice (all measured during the feeding period).	The dieting humans had 3% lower bodyweight at the end of the trial, visceral fat was trending lower and lean body mass was slightly higher.
IGF-1	Not applicable to yeast	Reduced by 45% at the end of the fast period, returned to normal within a week of re-feeding.	Reduced by 25% at the end of the fast period, remained somewhat reduced during re-feeding.
Insulin, glucose and ketones	Not applicable to yeast	Blood glucose dropped by 40%, insulin levels by 90% and ketones increased by 900% at the end of the fast period, these all returned to normal levels during the re-feeding period.	Blood glucose dropped by 11% and remained 6% below normal even during the re-feeding phase. Ketones increased by 370% and returned to normal during the re-feeding phase.
Inflammation and stress resistance	Fasting yeast were 100 times more resistant to hydrogen peroxide	This breed of mice is also very prone to severe ulcerating dermatitis, at a rate that requires 20% of control mice to be put down. In the fasting group this was only 10%.	C-reactive protein (a risk factor for inflammatory heart disease) was reduced in dieting humans.
Immune system health	Not applicable	Increasing age causes reduced production of adaptive immune cells in the control group. This normal decline is reversed in the fasting mice.	Not measured
Regeneration	Not applicable	Stem cell levels in the dieting mice increased a lot, likely to contribute to regeneration of cells and systems.	Possible increase in stem cells but not significant in the study.
Cognitive performance	Not applicable	Compared to the control mice, the dieting mice had enhanced cognitive performance, better motor learning, short term and long term memory. Evidence of promoted adult neurogenesis in the fasting mice.	Not measured

So it looks like this diet will probably promote a longer, healthier life with improved cognitive and physical function into old age. How do we do it, and how easy is it to do?

First, we need to cut calories from about 2400 kCal per day to about 725, only about a third of normal. Second, we need to reduce protein intake to only about 10% of those 725 kCal. Thirdly, despite this we need to get as much nutrition as possible to avoid running short of any essential nutrients and causing problems. I found that it was reasonably easy to achieve all of this by:

• only eating plant-based foods, mostly vegetables, vegetable soup made with chicken stock, and salads. I also had dietary fibre supplements (psyllium husk) as a substitute desert. 
• no high protein foods - so as well as no meat, also no mushrooms, beans or peas, tofu, eggs or dairy, or nuts
• carefully control fat and carbohydrate consumption to limit total calories to the target. I found it easy to exclude carbohydrate rich foods altogether (starchy vegetables and grains), and to carefully control fat consumption (maybe 40g per day, mostly as salad dressing and for stir-fried green vegetables.

Here is my typical fasting day:

Breakfast - a soy latte (a habit, I find it easier to manage the fasting phase if I dont give up all my normal habits).

Lunch - a plate of salad with vinaigrette from my cafe at work. Choose the low carb, low protein salads (no meat, beans, cheese, potato etc.). The vinaigrette is important to make it delicious. I figure it may be 10 to 20g of fat total, mostly in the vinaigrette, but this is a guess only.

Dinner - a bowl of cauliflower and leek soup, and some stir fried green vegetables (maybe another 10 to 20g fat).

Desert - 150g blueberries, psyllium husk jelly and 20g coconut cream.

I found this pretty easy to comply with, because it was all nice food and relatively filling. Another meal that works is ratatouille  - as long as you're careful with the oil in the recipe, the rest of the ingredients are all low carb, low protein and low energy. Having a significant fraction of allowable calories from fat seems to be important in making the food palatable.

Over the 5 days I felt a bit hungry sometimes, but not ravenously so, and never following a meal. My urine ketone levels went quite high, well above 5mmol/L. My weight dropped by about 1kg - which would correspond to using about 200g per day of stored fat to make up about 1800 kCal of daily energy deficit. I figure this means I got the diet about right without precise calorie counting each day.

I found this easier to do than the 5:2 diet, partly because the food quantity was higher and it was more palatable, and partly because you quickly get used to eating less. In the 5:2 diet, the diet day was always slightly traumatic and unsatisfying because each time it is a change from the day before.

So far, it looks like this is fairly easy to do. I'll post again next month with some real data and graphs.