Caloric restriction and fasting

Caloric restriction is usually associated with dieting, often combined with exercise – the ‘move more, eat less’ cliche. However, as I have mentioned elsewhere, even though this seems intuitive (calories in – calories out), the strategy fails because it ignores our biology. Rather than going into details here, I refer you to a more recent post on the topic of calorie restriction, which also describes an alternative (and better) model for weight loss and health – the carbohydrate/insulin model.

 

Ageing

However, there may be another role for calorie restriction – longevity. This was first recognised in mice and rats – chronically reducing calories by 20-40% throughout life can dramatically prolong lifespan (by a doubling or more).

caloric_restrictions_dallas_clouatreWhat is remarkable is that we now know this effect occurs across animal species and kingdoms, going right back to the simplest of organisms. It prolongs life in earthworms, flies, and yeasts (fungi), to name just a few. But it goes back even further. Energy restriction increases the lifespan of bacteria and other prokaryotes (precursors to the eukaryotes that comprise the cells in our bodies). If E.coli is placed in a nutrient-poor medium, it’s lifespan is prolonged by up to 4-fold. This can be reversed by introducing various nutrients, but importantly, not ketone-like nutrients.

So, it seems to be a universal law of biology – energy restriction prolongs the duration of life.

We can presume this applies to the human as well, however ethical, practical and lifestyle reasons have precluded definitive studies. Anecdotally, we can observe that people living to extremes of age are usually eating little and lean. However, it is questionable whether a life extended by chronic caloric restriction would be a life worth living – no one asked the mice whether it was fun (and they didn’t have a choice). Further, we live in an obeseogenic environment, calorie restriction some of the time might be manageable, but all of the time?

Why does calorie restriction prolong life? The ultimate objective of an organism is the replication and survival of its DNA. It takes energy to replicate, and energy for the replications to survive. Organisms have developed pathways to sense energy availability before making the choice to replicate, and these energy sensors are known and well-preserved across species. If sufficient energy is not available, organisms go into a maintenance mode for survival until energy becomes abundant again. Thus, calorie restriction prolongs lifespan. Lifespan is determined by the balance between replication now or later. Once replicated, the organism can die – successful replication determines lifespan.

Similar forces are at work in the human. We evolved to have a long post-reproductive lifespan so as to look after grandchildren while parents continued to hunt and gather. The driver is the imperative to ensure the survival of the offspring. After that, our DNA has no further need for us.

Fasting

Of course, the ultimate form of calorie restriction is fasting.

Voluntary periods of fasting are often dismissed as worrisome or dangerous, with concerns about triggering some sort of irreversible and terminal ‘survival response’, the breakdown of muscle protein for energy or other unspecified but damaging effects. This mistake comes about by thinking that fasting evokes the same metabolic response that calorie restriction does, only more extreme. That’s wrong.

intermittent-fasting-science-and-supplementation-v2-2-640xhWith calorie restriction, the response of the body is to reduce metabolic rate to match energy availability. Thus a 20% reduction in dietary calories will result in a 20% reduction in metabolic rate and the body will continue to survive until more calories become available. It is a form of ‘business as usual’ until better times. However, the body cannot do this during a fast because it cannot reduce metabolism to match available calories, which are now nil – that would mean reducing metabolic rate to zero (otherwise known as death).

So, it does the opposite. It either holds metabolic rate at pre-fasting levels, or increases metabolic rate to support action. It sends hormonal signals (e.g. adrenilin, growth factors) to preserve or increase muscle mass. It reduces muscle protein breakdown and turnover. It increases mental alertness (a true survival response, since it was only our brains that gave us the advantage over our prey). It turns to its fat stores to provide fatty acids to fuel muscles and substrates for the liver to make glucose and ketones (to fuel the brain). In short, it provides the organism with all the tools it needs to get out there and find some food. To do otherwise would mean a slow death by starvation.

Perhaps think of it in economic terms. A person has a full-time job, but decides s/he can manage with a 20% reduction in income, and changes from a 5-day working week to 4 days. This should be sustainable of the person has got the sums right. This is the equivalent of sustainable calorie restriction – reducing expenditure to match income.

Now, imagine a person with a full-time job who suddenly loses that job. Income now goes to zero. The person cannot reduce the cost of living to zero, and so cannot use the ‘calorie restriction’ response. Instead, there is an imperative to marshal all their resources and quickly find another job before any savings (fat) are depleted. They enter a ‘high-activity’ mode (corresponding to the fasting response). If they are not successful in finding employment, over a period of time destitution will set in (the equivalent of starvation).

image_intermittent-fasting-330x330In fact, without an adaptation to fasting we would have risked extinction. The dietary habits of our ancestors probably followed a feast-fast(famine) pattern. Certainly, food-availability would not have been constant for most. Multiple factors could impose periods of fast or famine, such as a lack of hunting success or prey availability, or environmental influences such as food scarcity during winter in higher latitudes or during drought. If we had not been able to adapt to these periods of fasting (or calorie restriction for that matter), we would not have survived the palaeolithic age and reached the supermarket age.

Fat

Our fat stores were crucial to that survival. Fat is lightweight (remember, it floats on water) and energy-dense (9 calories per gram, compared to only 4 for carbohydrate or protein). It is a remarkably efficient fuel source that we carry with us. While the body stores some carbohydrate (glucose) in the form of glycogen, it keeps only about a one-day supply. If there is no further dietary source for glucose after that, the liver manufactures it from fat (the glycerol backbone in triglycerides). It would be crazy for the body to turn to muscle proteins for energy while there are stores of fat, and fat can fuel metabolism for weeks or months. The longest documented period a human has gone without any food is 382 days. The dieter was extremely obese and undertook this fast (against medical advice) of his own free will as a last resort to reduce weight. He was medically-supervised, and turned out to only require the occasional vitamin/mineral supplement. During this period, of over a year, he reported being mentally-alert and that he had never felt better.

RunnerWhile this was an extreme case, it is important to realise that even lean people carry a considerable number of calories as fat. For example, lean marathon runners carry around 10% body fat (it’s there, it may not be visible though). The body needs about 5% for functions other than energy (for example, building cell walls). This leaves the runner with a 5% surplus, which is 3.5kg of fat for a 70kg male. Taking fat as containing 9 calories per gram, this equates to 9,000 calories per kilogram. This means that our lean runner is carrying 3.5×9,000 calories, or 31,500 calories everywhere he goes, asleep or awake. If that person was fasting, and had a daily energy need of about 2,000 calories, he could fuel this metabolism using his onboard fat for over a fortnight. Imagine what the rest of us could do!

Potential benefits

While fasting is usually thought of as a weight loss strategy, there can be other benefits. This should come as no surprise, given that the fasting response increases alertness and is a call to action. Compare that to the drowsiness and inactivity associated with feasting. Fasting can be particularly effective for type 2 diabetes, as it lowers blood sugar levels, reduces insulin levels, increases insulin sensitivity and releases stored fat. Fasting may be beneficial for auto-immune and auto-inflammatory conditions (and has been trialled in rheumatoid arthritis, for example). Fasting can reduce chronic inflammation in various ways – by reducing body fat (adipose tissue is metabolically active and releases pro-inflammatory agents) and by triggering the liver to make ketones. Fasting can be used to rapidly enter a state of ketosis that is then maintained on a ketogenic diet. As I have explained in previous posts, ketones are not just a fuel for metabolism but also signalling molecules that are neuro-protective, anti-inflammatory and immune regulators, and that may have a beneficial role in mental health and cancer. A further factor may be leaky gut – if foods (such as gluten or carbohydrate) are resulting in a leaky gut, then withdrawn of all food could restore the integrity of the gut wall and reduce chronic inflammation.

images-2Finally, fasting may give cells an opportunity to repair and revive. The 2016 Nobel Prize in Medicine went to Professor Yoshinori Ohsumi “for his discoveries of mechanisms for autophagy”, which roughly translates as self-eating. This is a normal and healthy process in which cells break down damaged or dysfunctional parts to clear the way for new synthesis to occur (a kind of spring clean). For example, amino acids recovered from this process can be used to maintain muscle protein. Autophagy may occur more strongly and effectively during fasting.

The benefits of fasting may explain why it is practiced so widely across cultures and religions, even though (or perhaps because) food supply became more reliable with time. Something that was once inevitable became codified. All major religions (with the exception of Protestant) incorporate some form of ritual fasting or food restriction – Christianity, Islam, Judaism, Hinduism, Buddhism, Orthodox, the list goes on and on. Millions of people safely fast annually. Spiritual awareness is an important aspect of these rituals (remember the increased mental awareness that comes from fuelling the brain on ketones). Early greek (and other) philosophers also fasted to heighten their thinking. The ‘cleansing’ claims may have some basis in autophagy.

Post-script

On a personal note, I have not deliberately fasted and I cannot offer a personal perspective on fasting. This post arose from my interest in the topic, and because of its close relationship to a ketogenic diet. My preference has been to get the benefits of a keto-adapted metabolism by adhering to a low-carbohydrate, high-fat diet (my objective has not been weight-loss). However, I can see the sense in combining intermittent fasting (say a weekly 24 hour fast) with a ketogenic diet. It will depend on an individual’s goals.jason-fung-book

If you have an interest in trying fasting or need to know more, I recommend Dr. Jason Fung’s book “The Complete Guide to Fasting”, which covers the science of fasting and provides practical step-by-step guides to the many ways there are to fast (there are multiple approaches, some of which include selective eating). His website also contains much insight and useful information.


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Note: The content of this post is intended to be educational and informative. It should not be taken as medical advice.