Fasting & Caloric Restriction
It is a rather personal story how I came to be interested in fasting as a therapeutic approach for symptom relief for my chronic fatigue syndrome. During a period of tremendous grief and earth shattering emotional stress, I came to realize not consuming food improved my daily symptoms. The loss of appetite and even nausea that comes with emotional upset is common. It is also common during such life events to sleep little, fall out of routine with health habits like supplements and medications, and generally neglect self-care that is so vital to those with chronic illnesses. I did all of these things and increased my activity level by working 7-days a week. After several harrowing weeks of sustained distress, I expected worsening fatigue, brain fog, and full relapse. Much to my surprise, I felt physically better than ever. I was working 3 jobs in NYC and starting my business. It was undeniable. My symptoms consistently, and significantly improved when I was not consuming.
From there ignited a tremendous interest in the literature surrounding fasting as a tool for various health conditions. I first proposed this dietary approach for those with ME/CFS in a prior post. You can read that here.
Fasting and Caloric Restriction
During this period I wasn’t intentionally fasting, in fact I ate whatever I wanted when I did eat. Usually not healthy food, but comfort foods. In reality, I was simply restricting calories—a process known as caloric restriction (CR).
It could be argued that fasting differs from CR in that fasting does not require overall reduction in calories. While this isn’t incorrect, generally speaking the scientific literature puts these two, CR and fasting, under the umbrella term dietary restriction, or DR. In turn, some of the best evidence for these eating patterns comes from trials that are reduced in calories. You won’t find much (I couldn’t find any) studies of fasting diets that are not lower in calories. Because of this, CR and fasting as terms can be used almost interchangeably.
It is possible to fast for 18 hours and then over consume foods for 6 hours to reach the recommended 2,000 calories per day. This may be indicated for some that struggle to maintain weight or those who are physically active, but keep in mind that the positive effects of CR or fasting seen in the literature are dependent on consuming fewer calories.
Why should I try fasting at all?
Caloric Restriction Is Neuroprotective. In animal models of aging and neurodegenerative diseases, CR protects neurons in the hippocampus and cortex and is associated with less age-related functional decline. In fact, studying the oldest populations of the world, like the people of Okinawa, they regularly consume less calories and have long lives with little disease. While many factors may influence their longevity, it is thought that CR is a major contributor.
Caloric Restriction is Anti-inflammatory. Neuroinflammation is related to aging and cognitive decline, but also neurodegenerative disease, chronic pain, mental conditions, and perhaps more. Central to neuroinflammation are specialized nerve cells, the astrocytes and microglia. Restricting calorie intake either by CR or intermittent fasting (IF) has been found to reduce the pro-inflammatory actions of astrocytes and microglia.
Caloric Restriction Blocks Inflammatory Cytokines. In rodents, CR or IF reduces neuroinflammation in the hypothalamus (hormonal control point, etc) and hippocampus (memory center) when exposed to an inflammatory stimuli, LPS. Also in rodents, CR reduces proinflammatory cytokines, NFkB, increases the nerve growth factor BDNF, and improves spatial memory. In humans, CR and IF improves inflammatory cardiometabolic markers of health such as insulin, blood lipids, and CRP.
Caloric Restriction is Good for Mitochondria. CR or IF stimulates protective gene activity (PGC1-alpha for the science readers) which prevents neuronal damage due to oxidative stress and stimulates production of new mitochondria. It also has the effect of stimulating gene activity (SIRT3 for the science readers) that increases antioxidant defenses. Reducing oxidative stress and upping defenses against existing oxidative stress, helps preserve neural tissues and allows for unhindered activity of neural stem cells.
Many of the same cellular and molecular mechanisms of CR and fasting are akin to that seen in the ketogenic diet since all three diet strategies increase β-hydroxybutyrate—a powerful signaling molecule.
Here’s my take on different fasting approaches. Note, that all of these allow for regular water intake.
Intermittent Fasting Protocols
Circadian Rhythm. This fast starts at sunset and lasts until morning. This method is completely dependent on having a structured sleep-wake cycle which is unlikely for most with chronic illness. This method may also be challenging to adhere to seasonally at Northern latitudes.
16:8 allows for 16 hours of fasting with an eating window of 8 hours. This protocol is easily achieved by skipping a meal. Choose breakfast or dinner, ideally dinner because of circadian rhythms. Increased blood ketones are not generally seen using this method unless regularly consuming a keto diet.
18:6 allows for 18 hours of fasting with an eating window of 6 hours. At this point there will be more production of ketones.
20:4 allows for 20 hours of fasting with an eating window of 4 hours.
I don’t recommend long term fasts of 36 hours or longer for most individuals. As expected, these periods of food deprivation are more risky. In those with ME/CFS for instance, long term fasts can dramatically reduce blood pressure and worsen orthostatic intolerance. There is also the potential for muscle wasting and severe weight loss which is counterproductive for anyone dealing with a chronic illness.
For those with ME/CFS and fibromyalgia I suggest a fasting protocol that increases blood ketones (18:6 and up) and ensures weight maintenance unless overweight. Starting with a less restrictive plan is recommended at first to ease into 18:6 and longer fasting periods.
What about other fasting protocols?
Everyone seems to have a varied method these days, with an accompanying book and trademark. However, consider that many of these methods are nearly identical to what is described above. For instance, The Warrior Diet fasting method is just the 20:4 method all dressed up with a sexy name. The 5:2 diet is simply a calorically restricted diet in which 2 days per week you consume 500-600 calories, and eat normally the remaining 5 days. The Fast Mimicking Diet is a patented diet plan that is essentially calorically restricted and encourages IF in the realm of the 16:8 or 20:4 methods above. The alternate day fast is a 24 or 36 hour fast.
My unpopular opinion is to not be fooled by fancy marketing. Keep things simple. FASTING SHOULDN’T COST MONEY. The above breakdown of protocols is sufficient for most everyone and allows flexibility. However, for those who are unable to prepare meals themselves, the fast mimicking diet is a helpful idea. Here, a week of meals to aid in the fast mimicking are pre-prepared and delivered to your door for a (steep!) price through Prolon. Otherwise, use the free app ZeroFast to keep track of your fasting protocol and take notes to fine tune your approach.
Caloric restriction and fasting has been known for over 3 decades to reliably reduce inflammation and slow aging in numerous animal models, including monkeys. However, in animals, CR and fasting often reduces immunity, leaving the animals prone to otherwise benign infection.
Is this also the case in humans? It doesn’t seem so. Here are some recent clinical trials.
A 30% reduction in calorie intake for a period of just 3 months improves memory performance in elderly individuals, in parallel with reduced fasting plasma levels of insulin and inflammatory marker, C-reactive protein (CRP). Impressive, though this study was not nearly long enough in duration.
It was once unheard of to conduct a CR or fasting study long term in humans. Designing such a study is very costly. Fortuitously, these studies are now being done. In 218 healthy non-obese adults (20-50 yr), some were assigned a 25% CR diet (n=143) or an eat as you like diet (n=75). They were all tested at baseline, 12, and 24 months. At 2 years, the CR group experienced 10% weight loss, reduced circulating inflammatory markers, including leptin, serum CRP, and TNF-α (a proinflammatory cytokine). During the study there was no significant increase rate of infections or immunocompromise. One small problem however, was that 26 participants withdrew from the study in the CR group. Long term CR is not easy to maintain. IF with a calorie reduction would likely produce better adherence.
Another high profile study from Duke University is the CALERIE (Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy) study. Here, a 2-year CR (25% reduction) in non-obese adults (n = 143) compared to an all-you-can-eat group (n =75) was well tolerated without increased incidence of infection. The CR group also reported improvements in mood and improved sleep quality.
A small (n=8) randomized, cross-over trial of pre-diabetic men following a 5 week 18:6 fasting method showed improved insulin sensitivity, blood pressure, sleep, oxidative stress, and appetite control without weight loss.
A pilot study of 16 multiple sclerosis subjects experiencing symptom relapse were enrolled and randomized 50:50 to an IF (every other day, similar to 20:4) or eat as you like control diet between 2014 and 2016. There was significant reductions in leptin, an inflammatory cytokine, and positive changes in the gut microbiome. There was also no reported adverse effects with improvement in MS symptoms but all participants continued with prescribed medications.
A 1 month study of alternate day fasting in 30 non-obese adults underwent a 6 month protocol of 36 hr periods without caloric intake followed by 12 hr intervals with as desired food consumption. Cardiovascular risk factors were improved and body weight composition improved. There was also increased β-hydroxybutyrate, even on non-fasting days. There were no reported adverse effects.
What about Hormones?
The CALERIE study also examined changes in hormone levels due to CR. There were changes in luteinizing hormone, total testosterone, and follicle-stimulating hormone but they did not differ significantly between the groups. They were not statistically significant.
Studies in Ramadan-style fasting (usually a 16:8 or a more restrictive method) showed no significant changes in thyroid hormones in men or women. Of note, Ramadan fasting does not allow for water intake and is opposite the circadian rhythm method—so not completely comparable to other methods. Nonetheless, it is unlikely that intermittent fasting protocols produce any significant detriment to thyroid hormone levels or function. Longer fasts (36 hr or more) have consistently shown thyroid hormone depression however and cannot be recommended. In alternate day fasts—36 hr fasting periods followed by 12 hr eating window, there was reduced T3 over the 4 week study but overall thyroid function was not affected.
Fasting isn’t for everyone.
Some people are absolutely not encouraged to undergo fasting protocols. This includes pregnant and lactating women, growing children, those with history of eating disorders, poorly controlled diabetics (Type I & II), the elderly, those who are underweight, those on medications that must be taken with food such as antibiotics. Should you need professional help with fasting approaches, consider a consultation.
Bok E, et al. (2019) Dietary Restriction and Neuroinflammation: A Potential Mechanistic Link. Int J Mol Sci. 20(3). pii: E464.
Pani G. (2015) Neuroprotective effects of dietary restriction: Evidence and mechanisms. Semin Cell Dev Biol. 40:106-14.
Witte AV, et al. (2009) Caloric restriction improves memory in elderly humans. Proc Natl Acad Sci U S A. 106(4): 1255–1260.
Meydani SN, et al. (2016) Long-term moderate calorie restriction inhibits inflammation without impairing cell-mediated immunity: a randomized controlled trial in non-obese humans. Aging (Albany NY). 8(7): 1416–1426.
Martin CK, et al. (2016) Effect of Calorie Restriction on Mood, Quality of Life, Sleep, and Sexual Function in Healthy Nonobese Adults: The CALERIE 2 Randomized Clinical Trial. JAMA Intern Med. 176(6):743-52.
Sutton EF, et al. (2018) Early Time-Restricted Feeding Improves Insulin Sensitivity, Blood Pressure, and Oxidative Stress Even without Weight Loss in Men with Prediabetes. Clinical and Translational Report. 27(6): P1212-1221.E3.
Azizi, F. (2015) Islamic Fasting and Thyroid Hormones. Int J Endocrinol Metab. 13(2): e29248.
Cignarella F, et al. (2018) Intermittent Fasting Confers Protection in CNS Autoimmunity by Altering the Gut Microbiota. Cell Metab. 27(6):1222-1235.e6.
Stekovic S. et al (2019) Alternate Day Fasting Improves Physiological and Molecular Markers of Aging in Healthy, Non-obese Humans. Cell Metab. pii: S1550-4131(19)30429-2.