Intermittent Fasting—Fad or Treatment Option?

“Intermittent fasting” has become a trendy term that means voluntarily not eating for specific periods of time.¹ It can mean going for a certain number of hours without food during the day or night or even multi-way fasts.  In 2013, Mosley and Spencer published a best-selling book titled, The Fast Diet, which touted benefits of energy intake severely reduced for two days a week while eating normally the rest of the week.² Since then there has been a plethora of popular press publications on the topic of intermittent fasting.

The big appeal for the public is it doesn’t involve counting calories because the focus is not on what you eat but when you don’t eat. Researchers have a different focus; they are looking into positive health outcomes in weight and metabolic parameters associated with type 2 diabetes, cardiovascular disease, and cancer.

Defining Intermittent Fasting Methods

Researcher Patterson and colleagues have an easy to understand breakdown of the major intermittent fasting methods.³

• The “complete alternate day fasting” method is where fasting is done on alternating days and food is consumed ad-libitum on non-fasting days.
• Then the “modified fasting” method is the basis for the 5:2 diet, which involves severe energy restriction for two non-consecutive days a week and ad libitum eating the other 5 days.
• Then the “time-restricted feeding or eating” method is where you can eat food within a specified timeframe, or fast and go without any food for a specified time frame on a routine basis.
• The fourth method encompasses religious fasting, which includes a wide variety of fasting protocols pursued for religious or spiritual purposes.

Most of the data to support intermittent fasting involve animal studies. There have been a limited number of human intervention studies.  More studies are needed to confirm the long-term benefits of the different methods.

The rest of this article will focus on the “time restricted feeding or eating” since this method has some recently published human studies that show positive management of health and patient compliance. It is also the easiest one to follow between all the intermittent fasting methods.

Why Time Restricted Eating Holds Promise

Time restricted eating and time restricted feeding are used in the literature interchangeably.  Typically “feeding” is referenced when animal studies are being described and “eating” for human intervention studies.

Time restricted eating involves eating during an 8 – 12 hour window which means your body fasts for 12 -16 hours during a 24 hour period. The beauty of this longer fasting time is it allows the body to engage and complete repair cycles like reducing oxidative stress and inflammation, including clearing away damaged cells.⁴

Unfortunately, when food is eaten during this fasting period the body must turn off or put on hold some of the repair processes underway and reallocate body resources to digesting and absorbing the food just eaten. This takes away from this critical repair phase needed for optimal health.

The body has two major systems that are turned on when food is consumed that are significantly affected once an individual eats during this 12 – 16 hour fasting period. ³ One is the body’s circadian clock, which is primarily regulated by light/dark signals received by the retina. The other is the gastrointestinal (gut) microbiota – the complex, diverse, and vast microbial community that resides in the intestinal tract.

Circadian Clocks – We Have Multiple Clock Systems

Nearly all physiological processes in our bodies are subject to daily cycles that are directed by a circadian timing system. This circadian clock refers to a 24-hour cycle where there are physical, mental, and behavioral changes prompted by light and darkness. This timing system is made up of multiple clocks that can be divided into 2 parts: one master central clock, located in the brain’s hypothalamus, and multiple peripheral clocks which are in cells outside the brain. ⁵

In truth, circadian clocks are found in all cells of various organs. However, the master circadian clock plays a major role in many metabolic processes like regulation of core body temperature; regulation of the hormones: melatonin, growth hormone, and cortisol; and regulation of appetite and metabolic rate.⁵

The second clock system is the peripheral clock and it plays an integral and unique role in each of its respective tissues, driving the circadian expression of specific genes involved in a variety of physiological functions like carbohydrate, lipid, and cholesterol metabolism that take place in the liver.⁵

The central clock controls the peripheral clocks, which also can be turned on and off by food or lack of food. For example, in the morning, the central clock responds to light turning on and off systems.  If you don’t eat and continue to go without food throughout the day, your peripheral clocks pick up on this and becomes desynchronized with the circadian master clock. Animal research indicates a resultant disruption of glucose homeostasis in the liver. ¹⁵

Research is finding by eating at times that supports synchronicity between both these circadian driven systems can help protect an individual from disease.  Research is also indicating that long-term disruption of these circadian rhythms is harmful to an individual’s health.

Gastrointestinal Microbiota

We are just starting to understand better the gastrointestinal tract’s processes that are tied to our body’s circadian timing. We know the microbes in our gastrointestinal gut are not static.  They change from morning to evening. So we essentially go to bed with one set of bacterial cells and wake up in the morning with a different set of bacterial cells in our guts. ¹⁶

What we don’t know is whether the gastrointestinal microbes simply respond to our own body’s circadian rhythm or whether they can actually exert influence on our own rhythm somehow. The implications for health are huge.  Think about the many important physiological functions such as digestion and metabolism of foods; immune responses and inflammation; and how disruption of the gut microbiota might then contribute to a variety of conditions including childhood asthma, obesity, colitis, and colon cancer.

Gastrointestinal microbiota circadian rhythms appear to be primarily influenced by the timing of food intake and composition of the diet.⁶ More research in humans is needed to understand the full effect on our health, in particular how erratic meal consumption and late night eating disturb gastrointestinal microbiota circadian rhythms and have systemic effects on the body.  Right now most the research is from studies on mice.

Body Cleaning During Fasting

When you go without food for a period of time, the body stimulates metabolic changes that are a natural cleansing process known as autophagy, in which our bodies detoxify and remove damaged cells. One major part of the autophagy process includes lysosomes picking up damaged cells, damaged mitochondria, and cancerous cells, and disposing of them. During the fed state, when insulin levels increase, the rate of autophagy is low. During the fasted state, as insulin levels drop, autophagy increases dramatically, depending on the length of the fast.⁷ Any food consumed during this fasting period interrupts and derails this cleaning process.

From a practical application standpoint, if you start eating or drinking at 8 am and have your last bite at 9 pm or later, your clock is running for a long time, 13 hours or more. Research is discovering that the 11 hour fasting window (24 hours minus 13 hours of eating) is not enough time for your body to perform various cleaning and repair functions required for optimal health. For example, just the act of eating food and having to metabolize it causes potential damage in the body by secreting free radicals. The body repairs itself during the critical fasting time while you are sleeping!

Human Studies and Time Restricted Eating Health Outcomes

In the limited number of trials done with humans, study results have been mixed in regards to weight.⁸ More human research is needed.  In regards to optimal metabolic function there appears to be positive improvements for insulin, fasting glucose, cholesterol, and triglyceride levels.^7,8,9 These are all positive for reduction in cardiovascular disease risk.

Next Best Thing After Human Studies

As you are aware, human trial research is costly, takes years to obtain funding, to implement, and to publish results.  To get around this, researchers have cleverly shed light on time restricted feeding by looking at data from large past population studies.

Researchers examined the 2009 – 2010 National Health and Nutrition Examination Survey (NHANES) data for nighttime fasting associations with various health biomarkers. Results showed longer fasting periods at night were associated with decreases in HbA1c.¹⁰ Also, significant associations were found between eating in the later evening and biomarkers of generalized inflammation.¹¹ This was a large sample of subjects giving these findings credibility; however, randomized trials are still needed to confirm the associations found in the data.

Other recent research has found links between altered circadian clocks and promotion of multiple cancers, most notably, breast cancer. In the breast, circadian clocks regulate the expression of genes. Disruption of the circadian rhythms alter breast biology and may promote cancer, according to recently published studies.¹²

A study looked at data from the Women’s Healthy Eating and Living Study for   breast cancer recurrence and survival.  The researchers found that fasting for fewer than 13 hours per night was associated with a 36% higher risk of breast cancer recurrence compared to fasting 13 or more hours per night. Fasting for fewer than 13 hours per night was not associated with better survival for breast cancer or any other disease. The researchers also found that fasting for fewer than 13 hours per night was associated with less sleep and higher levels of HbA1C.¹³ It is important to note that this study was not randomized and the data depended on the women accurately remembering what they ate and when they ate it.

Regardless of the studies’ potential limitations, night time fasting holds strong promise for positive outcomes for breast cancer, other cancers, diabetes management biomarkers, and even low-grade inflammation which is linked to heart disease.^{11, 12, 13}  This is positive news for both patients and clinicians.

What Fasting Window to Use for Patients

Evidence supports intermittent fasting as a safe, effective, and feasible practice for patients to improve cardiovascular and diabetes markers and for reduction in risk and recurrence of breast cancer.^{11, 12, 13}

A 13-hour fasting window was the most widely used measure in the research. However, a longer fasting duration was associated with improved glycemic regulation. The upper fasting time was 16 hours.¹³ As a clinician, I would not discourage patients from trying it, if they can easily adapt their lifestyle and are interested in longer than 13 hours without food. Typically, the fasting window starts in the early evening, a couple hours before bedtime.

Research is looking at additional factors like rigorous exercise in the morning, eating two meals verses several small meals throughout the day, and even how to adapt for shift workers.

Are Coffee and Tea Allowed?

Once you start recommending intermittent fasting to patients, you will get questions about whether coffee or tea are allowed during the fasting window. There is no indication that drinking black tea or coffee stops autophagy; however, people respond differently to caffeine and there will be some stimulation of the digestive tract and even changes in microflora in the body both for tea and coffee. The caffeine will disrupt melatonin production which is part of the circadian melatonin process.¹⁴

This disruption is not significant during the fast. I would be far more concerned with a late night food snack or the addition of milk or sugar to the beverage than the actual coffee or tea. Instead, I recommend assessing their compliance and if the desired beverage brings them pleasure, or if it will be too challenging for them to stop. I would avoid caffeine in the evening before or during the fast.

Good News All Around

It is reassuring to have a nutrition therapy you can recommend to patients that is easy, effective according to early research, and doesn’t require significant disruption to their lifestyle.

by Teresa Pangan, PhD, RDN

References

1. Fredericks, K (n.d.). Proven Benefits of Intermittent Fasting | Reader’s Digest – Reader’s Digest. Retrieved January 01, 2018, from https://www.rd.com/health/ wellness/intermittent-fasting-benefits/
2. Mosley, M, & Spencer, M (2015). The FastDiet: lose weight, stay healthy, and live longer with the simple secret of intermittent fasting. New York: Atria Paperback.
3. Patterson, R, Laughlin, G, Lacroix, A, Hartman, S, Natarajan, L, Senger, C, Gallo, L (2015). Intermittent Fasting and Human Metabolic Health. Journal of the Academy of Nutrition and Dietetics,115(8), 1203-1212. doi:10.1016/j.jand.2015.02.018
4. Longo, V, Panda, S (2016). Fasting, Circadian Rhythms, and Time-Restricted Feeding in Healthy Lifespan. Cell Metabolism,23(6), 1048-1059. doi:10.1016/j.cmet.2016.06.001
5. Albrecht, U (2012). Timing to Perfection: The Biology of Central and Peripheral Circadian Clocks. Neuron,74(2), 246-260. doi:10.1016/j.neuron.2012.04.006
6. Thaiss, C (2016). The Microbiome Waltz – cross-regulation of rhythmic oscillations at the host-microbiota interface. Endocrine Abstracts. doi:10.1530/endoabs.41.s15.1
7. Mattson, M, Longo, V, Harvie, M (2017). Impact of intermittent fasting on health and disease processes. Ageing Research Reviews,39, 46-58. doi:10.1016/j.arr.2016.10.005
8. St-Onge, M, Ard, J, Baskin, M, Chiuve, S, Johnson, H, Kris-Etherton, P, Varady, K (2017). Meal Timing and Frequency: Implications for Cardiovascular Disease Prevention: A Scientific Statement From the American Heart Association. Circulation,135(9). doi:10.1161/cir.0000000000000476
9. Timing meals later at night can cause weight gain and impair fat metabolism. (2017, June 02). Retrieved 1/01/2018, https://www.sciencedaily.com/releases/2017/06/ 170602143816.htm
10. Marinac, C, Natarajan, L, Sears, D, Gallo, L, Hartman, S, Arredondo, E, Patterson, R (2015). Prolonged Nightly Fasting and Breast Cancer Risk: Findings from NHANES (2009-2010). Cancer Epidemiology Biomarkers & Prevention,24(5), 783-789. doi:10.1158/1055-9965.epi-14-1292
11. Marinac, C, Sears, D, Natarajan, L, Gallo, L, Breen, C, Patterson, R (2015). Frequency and Circadian Timing of Eating May Influence Biomarkers of Inflammation and Insulin Resistance Associated with Breast Cancer Risk. Plos One,10(8). doi:10.1371/ journal.pone.0136240
12. Blakeman, V, Williams, J, Meng, Q, & Streuli, C (2016). Circadian clocks and breast cancer. Breast Cancer Research,18(1). doi:10.1186/s13058-016-0743-z
13. Marinac, C, Nelson, S, Breen, C, Hartman, S, Natarajan, L, Pierce, J, Patterson, R (2016). Prolonged Nightly Fasting and Breast Cancer Prognosis. JAMA Oncology,2(8), 1049. doi:10.1001/jamaoncol.2016.0164
14. Burke, T, Markwald, R, Mchill, A, Chinoy, E, Snider, J, Bessman, S, Wright, K (2015). Effects of caffeine on the human circadian clock in vivo and in vitro. Science Translational Medicine,7(305). doi:10.1126/scitranslmed.aac5125
15. Li, M, Ruan, H, Hughes, M, Lee, J, Singh, J, Jones, S, Yang, X (2013). O-GlcNAc Signaling Entrains the Circadian Clock by Inhibiting BMAL1/CLOCK Ubiquitination. Cell Metabolism, 17(2), 303-310. doi:10.1016/j.cmet.2012.12.015
16. Thaiss, C, Zeevi, D, Levy, M, Zilberman-Schapira, G, Suez, J, Tengeler, A, Elinav, E (2014). Transkingdom Control of Microbiota Diurnal Oscillations Promotes Metabolic Homeostasis. Cell, 159(3), 514-529. doi:10.1016/j.cell.2014.09.048