When should I eat?

 When should I eat?

This is a question that I never would have thought to ask as I was growing up. As a child, I was fed breakfast, lunch and supper plus some snacks in between. I grew up “knowing” that breakfast was the most important meal of the day, lunch was a small meal eaten in the middle of the day and was often consumed while doing something else and supper was the sit-down meal, which was eaten with my family around 6 PM. The term “dinner” wasn’t used often and when it was, usually it was synonymous with supper. As kids we were told that we should eat a balanced diet and occasionally our teacher would tell us what the “government” meant by discussing the guidelines that had been sent to her. As I have adapted to retirement, I have started to think about what to eat and when to eat. I’ll tackle the latter in this entry and leave the former until a later day.

In the last year or so, I have read a couple of "health" books such as Lifespan by David Sinclair who makes a case for inhibiting/reversing aging, and The End of Alzheimer's by Dale Bredesen, who promotes a recipe for preventing Alzheimer Disease. Then there are more convincing writings including de Cabo and Mattson’s "Effects of Intermittent Fasting on Health, Aging, and Disease" (New Engl J Med 381: 2541, 2018), and Malinowski et al "Intermittent Fasting in Cardiovascular Disease- An Overview" (Nutrients 11: 672, 2019). Both of the latter articles describe the health benefits of fasting but let me start thousands of years ago when humans survived as hunter-gatherers.

Our hunter-gatherer ancestors are thought to have fed themselves on a completely opportunistic basis, eating whatever they could put their hands on and whenever it was available. This suggests that they might eat a lot of meat today, a lot of plant food a few days hence and perhaps not much in between. In other words, they lived a feast or famine lifestyle. Accordingly, fasting was something that was imposed upon them and not a choice, at least that is the argument made by some who study the topic. This leads to the idea that human bodies are made to accommodate eating well at times and fasting at other times. Since humans have left their caves, various religions have developed and this has resulted in the ritual of fasting for various occasions. To the best of my knowledge adherents of all the world’s major religions may fast for certain religious events. Thus, fasting is a “normal” practice and is probably not harmful to our health. Now some authors suggest that it is not just innocuous but is beneficial for our health. Before going further, I would like to explore what is meant by fasting.

A dictionary definition of fasting is abstaining from food. But what does this mean in terms behaviour that might extend one’s healthspan. After reading papers in research journals and watching videos, it is apparent that there are many forms of fasting and that fasting means different things to different people. A useful way to examine the meaning of fasting might be to looking at some of the terms related to fasting.

• Dry fast- not eating any food or drinking any liquid for a set period of time. Most fasts are not dry and allow one to drink water or even liquids without significant caloric content.

• Time restricted feeding- a schedule in which one abstains from food for a set period combined with a period for eating; for example fast for 16 hours and eat during an 8 hour window.

• Intermittent fasting- a form of time restricted eating that is done on a regular schedule. This might comprise eating only between 11 AM and 7 PM and not eating the rest of the day. Some people do this on a daily basis while others schedule it for certain days of the week. Before this term was coined, there were people who “never eat breakfast”; assuming that they ate only lunch and supper, they could well have been fasting for 16 hours/day without thinking about it.

• Alternate day fasting- in this form of fasting, food is not restricted on one day and this is alternated with a day of no food or sometimes a limited amount of food- say 25% of usual calories.

• 5:2 Intermittent Fast- herein one eats liberally on five days of the week and fasts on the other two.

As you can see from these examples, fasting can take many forms and be designed to fit one's particular needs and circumstances.

Health benefits of fasting. According to those who have studied the effects of fasting (either formally or informally), there are multiple benefits of fasting. For me the most interesting is the possibility that it may protect my brain from dementia. Nevertheless there are other benefits that are more tangible and based on more readily measured outcomes; these include weight loss, cardiovascular health and control of type 2 diabetes. These are described well in the papers by de Cabo and Mattson and Malinowski described above so I won’t detail them further here. I would just like to point out that there does not seem to be any way to monitor how any of these practices are warding off dementia or even a surrogate marker for dementia. In comparison, for those who are interested in weight loss, it is easy to step on a scale and weigh one’s self. If you are pursuing cardiovascular benefits, you may wish to take your blood pressure or have you blood lipids, such as LDL (low density lipoproteins)' checked by a lab test. Diabetics have the option of checking blood sugars or insulin levels.

Is there a physiological rationale for fasting? Until recently, I hadn’t considered the possibility of fasting to improve or maintain my health, so let me describe some of the things that I have learned. In basic biochemistry and physiology courses, I had learned that the most important sources of fuel for the human body were glucose and fats. I’ll discuss these in more detail in a subsequent blog entry. But for now let’s assume that glucose is used preferentially and when the body stores of glucose are expended, it starts to use its fat resources. If we start monitoring blood glucose concentrations immediately after the last meal of the day, it would climb to peak in minutes to hours depending on the food ingested and then decline thereafter. If you actively burn up this glucose with exercise its rate of decline will be faster. Suppose you finish your meal at 6 PM, your body may have used up all the glucose in perhaps 10-12 hours, meaning that it could have switched to burning fat around 4 to 6 AM the next day. When this happens, your body starts to utilize fat by converting some of the fatty acid stores into smaller molecules known as ketones or ketone bodies (beta hydroxybutyrate and acetoacetone). When this happens a process called autophagy increases within your cells, and this triggers the health benefits.

Autophagy literally means eating oneself- from the Greek auto for self and phagein for eating. One way to think about this is to consider the cell to be an amazing machine that repairs itself. As parts of the cell wear out or become damaged, they are removed and replaced with new parts. Autophagy is the process of removing the old parts by eating or digesting them. If disease or aging is caused by cellular parts wearing out and not being replaced adequately, then you can envision how enhancing autophagy might preserve health, ward off some diseases and slow the appearance of aging.  It is with this train of thought that I have considered fasting to protect my brain.

It appears that autophagy is enhanced by fasting when the body has depleted its glucose stores and starts to consume its fat stores and making ketones- that is to say it enters ketosis. Some might ask “why does ketosis stimulate autophagy?” The answer may lie in our ancestral experiences of feast or famine, but this is beyond the scope of this blog so I’ll stop here for the day. Perhaps one of you readers would like to take on describing it more detail. Here is a diagram from Experimental & Molecular Medicine volume 44, pages69–72(2012)