I have my diet pretty dialed in, but I also pay attention to when my body needs a change.  Many people adjust food and experiment with recipes.  I play with biochemistry.  In short, if I can eat or do something that’s going to improve immunity, reduce inflammation or improve mitochondrial function, then I’m going to give it a go.  Well, recently I’ve become interested in cellular degradation.  It’s the state where cells become worn out and dysfunctional. And as we all know, too many faulty parts encourages metabolic dysfunction and cancerous growths thereby decreasing longevity.  So, here's my question. “What’s the best way to clear away bad or damaged cells?”

Impact of Circadian Rhythms and Fasting on Health

First, a little context.  Research has shown that when adults consume meals of exactly the same macro nutrient content and caloric amount, glucose levels are lowest after breakfast and highest after dinner…even though meals are 100% identical.  This suggests that metabolism changes throughout the day.  Similarly, we also know that metabolism is guided by an internal clock making it more active during the day for eating, exercising and working and less active at night for recovery.  Now, while the external cue of light/dark helps set our brain’s active/rest states, there is another on/off switch…namely food.  Food, in fact, is the oscillator that governs the circadian rhythm of the liver and peripheral tissues and regulates the body’s protein synthesis and protein break-down programs.  In short, when you eat food, the body’s resources are mobilized to digest and absorb nutrients.  Whereas when you go without food for a period of time (aka fasting), the body switches to a natural cleansing process to rid itself of dysfunctional and damaged cells.

Out With the Old…In With the New

While fasting is a common method for reducing calorie intake to lose weight [1, 2], Dr. Rhonda Patrick (biochemist and scientist) says, its real benefits lie in its ability to ‘clean house’ and make room for new cell and tissue growth.  She says, “When a cell is damaged, it can die, but if it doesn't die, sometimes it becomes what's called senescent, and this happens a lot with aging.  What that means is that the cell is not dead, but it's not really alive either.  t's not doing its function.  It's just kind of sitting around in your body secreting pro-inflammatory molecules, things that are damaging other nearby cells thereby accelerating the aging process because inflammation drives aging in so many different ways.  Autophagy clears away those cells that are just sitting there creating damage and not doing much else, which is nice because that's also a very important biological mechanism for staying healthy."   Besides triggering autophagy, fasting also:

• Stimulates Immune Function and Stem Cell Generation – For years, fasting has been a dietary strategy for cancer patients.  Why?  According to Valter Longo (researcher, professor and Director of the USC Longevity Institute), prolonged fasting (>24 hours) forces the body to use its stores of glucose, fat and ketones, and it breaks down a significant portion of white blood cells and the gene PKA.  He says, “PKA is the key gene that gives the OK for stem cells to begin proliferating and rebuild the entire system. … And the good news is once the body gets rid of the parts of the system that might be damaged or old (even a system heavily damaged by chemotherapy or aging), it can literally generate a new immune system.”[3]  Other studies also suggest that fasting reduces the risk of breast cancer [4, 5] and minimizes the increase in inflammatory markers like CRP (C-Reactive Protein) which is important for mature adults to dial in to improve overall longevity.

• Reduces the Amount of Free Radicals – Another effect of fasting is that it lowers the amount of free radicals in the body.  In fact, some experts believe when cells are supplied with fuel, when fuel is not needed, cells leak electrons that react with oxygen producing free radicals which damage cells and mitochondrial DNA.  (Remember, how quickly your body ages largely depends on how well the mitochondria work…so minimizing this type of cell damage is critical.)  One of the best ways to combat mitochondrial free radical production is by consuming foods rich in anti-oxidants (e.g., goji berries, raw cacao, elderberries, pecans, wild blueberries, etc.), but another effective strategy is to limit the time and amount of food you consume.

Fasting Schedules…Eeny, Meeny, Miney, Moe

First, it’s important to note if you suffer from insulin dysregulation, chronic hypothalamus-pituitary-adrenal disruption, thyroid disorders, anxiety, are pregnant or breast-feeding, you probably shouldn’t fast.  Having said that, here are three popular fasting schedules.

• Prolonged Fasting (aka 5 Days) – Although the most challenging, one study [6] demonstrated that people who fasted for 5 consecutive days in a row saw improvements in biomarkers for cell regeneration and reduced risk factors for diabetes, cancer and cardiovascular disease.  The principal downside of this schedule is that it can raise cortisol levels causing the body to hold onto fat despite eating well and exercising.

• Alternate Day Fasting (aka 1:1) – It’s just like it sounds.  You eat for one day, followed by one day of not eating.  The key benefit of this schedule is some find this schedule easier to adhere to.  The principal con is that this plan does not align well to fuel needs for hard exercise and/or can lead to binging on eating days.

• Intermittent Fasting (also called Time-Restricted Eating) – With this schedule, eating is constrained to an 8-10 hour window (usually earlier in the day so it’s aligned with the body’s circadian rhythms).

Best Practices for Implementation

According to Dr. Patrick, regardless of your actual age, how old you look corresponds with key biological biomarkers (e.g., telomere length, DNA damage, cholesterol LDL, glucose metabolism and insulin sensitivity), which are all largely driven by the health of the mitochondria.  Yes, eating the right nutrients and exercise are important for promoting mitochondrial health, but fasting is the mechanism that triggers the body to rid itself of unwanted cargo.  Hence, she advocates the following:

• Avoid eating at night – While some use the 16:8 (fasting/eating) schedule, she says a 14:10 fasting/eating window is equally effective.  In fact, she eats upon waking and then stops eating by 5 or 6pm each day as adding excess fuel at bedtime will generate excessive free radicals that damage tissues.

• Drink ONLY water during fasting windows – While most of the literature loosely defines fasting as ‘restricted calories in liquid form’, that’s not accurate.  If you have a glass of wine, cup of tea or bone broth at night…or even a cup of coffee in the morning, that’s breaking the fast.  Remember, in order to turn ‘on’ autophagy (genetic program to clear away bad cells and minimize aging of other cells), food or lack thereof is the oscillator for the peripheral tissues.

• Eat your daily allotment of macronutrients/calories – Some people rationalize that if they don’t have time to eat during the day… and then hit the fasting window, they should skip eating altogether.  This is a bad approach…especially for fitness-minded adults.  Restricted eating does not mean restricted calories.  In order to continue to build muscle and perform at your best, job #1 has to be fueling the body with the all the nutrients it needs regardless of time of day.

• Pay attention to how you feel – Maintaining balanced blood sugar is a problem for many mature adults.  So, regardless of the schedule you choose, watch for any hypoglycemic symptoms (e.g., excessive sweating, lightheadedness, shakiness, anxiety, nausea, mental confusion, tingling in hands or feet). And if at any time you feel like you’re crashing, eat something.

Now, I also asked my friend, advanced functional medicine practitioner and nutritionist Tom Malterre for his opinion.  He says of course the body needs periods of rest and non-eating, but he’s not convinced that it needs to be programmed.  He says the body is ingenious…constantly triaging itself, sending and creating nutrients when and where it needs them, as well as ridding itself of toxins and dysfunctional cells.  Because metabolism, digestive enzyme, hormone and neurotransmitter production all go down with age, however, he recommends adults experiment with meal size and timing to make sure they're allowing the body the best opportunities to utilize fuel.  For example, many of his clients eat their biggest meal at breakfast and don't eat 3 hours before bedtime.  He says although some of those things may be considered a form of time-restricted eating, his motivation is to help people align food intake with their body’s digestion and absorption capacities…so fuel is available when it’s needed.

Bottom line, while fasting likely encourages the body’s cleansing and cellular regeneration processes (aka autophagy), it’s probably not the only mechanism.  If it speaks to you, then give it try, but make sure you focus on eating the food that works for your body.  That’s the most important thing to consider for optimizing cognitive and physical performance with a youthful vibrancy throughout life.

[1] Hatori, M., Vollmers, C., Zarrinpar, A., DiTacchio, L., Bushong, E.A., Gill, S., Leblanc, M., Chaix, A., Joens, M., Fitzpatrick, J.A., et al. (2012). Time-restricted feeding without reducing caloric intake prevents metabolic diseases in mice fed a high-fat diet. Cell Metab. 15, 848–860.

[2] Heilbronn, L.K., Smith, S.R., Martin, C.K., Anton, S.D., and Ravussin, E. (2005). Alternate-day fasting in nonobese subjects: effects on body weight, body composition, and energy metabolism. Am. J. Clin. Nutr. 81, 69–73.

[3] Wu, S. (June, 2014). Fasting triggers stem cell regeneration of damaged, old immune system. USC News.

[4] Marinac, C.R., Natarajan, L., Sears, D.D., Gallo, L.C., Hartman, S.J., Arredondo, E., and Patterson, R.E. (2015a). Prolonged nightly fasting and breast cancer risk: findings from NHANES (2009-2010). Cancer Epidemiology. Biomarkers Prev. 24, 783–789.

[5] Marinac, C.R., Sears, D.D., Natarajan, L., Gallo, L.C., Breen, C.I., and Patterson, R.E. (2015b). Frequency and circadian timing of eating may influence biomarkers of inflammation and insulin resistance associated with breast cancer risk. PLoS ONE 10, e0136240.

6] Brandhorst, S., Cheng, C. W., Childress, P., Choi, I.Y., Cohen, P., Conti, P. S., Di Biase, S., Dorff, T. B., Dubeau, L., Groshen, S., Ikeng, Y., Ji, L., Kennedy, B. K., Longo, V. D., Mirisola, M., Mirzael, H., Morgan, T. E., Navarrete, G., Odetti, P., Park, R., Penna, F., Perin, L., Sedrakyan, S., Vinciquerra, M., Wei, M., Yap, L. P. (June, 2015). A periodic diet that mimics fasting promotes multi-system regeneration, enhanced cognitive performance and health span. Cell Metabolism.