When a low carbohydrate diet is started, weight loss usually occurs rapidly and easily. Although the initial loss is partly water weight, with consistency, body-fat loss continues until ideal body weight is reached. This usually happens without much discomfort. 

There are occasionally exceptions to this experience. I previously recommended staying well hydrated, not being afraid to eat fat, and adding a little extra salt to improve the transition to a low carbohydrate diet. Metabolically, your body is designed to switch over to fat burning when carbohydrates are restricted, and this transition occurs over a matter of weeks. 

But some people have a difficult time sticking to this plan. Hunger doesn't always diminish. Eventually willpower is exhausted. What is going on?

This happens most often in people that have struggled with weight for a long time. This could be long-standing obesity or yo-yo dieting. 

INSULIN CAUSES OBESITY

I previously discussed the importance of insulin in weight loss/gain. Gary Taubes in "Why We Get Fat And What To Do About It," makes a very well supported argument that elevated insulin causes us to gain weight, and makes it difficult to reduce weight, even with calorie restriction. Recall that carbohydrates are the primary driver of insulin. A low carbohydrate diet reduces insulin levels and thus allows weight loss. 

INSULIN RESISTANCE
​
Jason Fung in "The Obesity Code" discusses the importance of insulin resistance. This is a common problem and often underlies difficulty with weight loss. 

Our bodies maintain homeostasis. That means they adjust to the situation to maintain consistency. Let's see how this works with insulin. When a person eats a meal containing carbohydrates, their blood glucose level will rise. To maintain homeostasis (consistent blood glucose level) the pancreas secretes insulin. This elevated insulin level drives the blood glucose into cells to be burned as energy or stored as fat. It simultaneously stops mobilizing fat from storage since energy is plentiful. This is all good. 

Now let's assume the person eats a high carbohydrate diet consistently, just as recommended by the government. The insulin level is elevated throughout the day. Because insulin drives glucose into cells, the blood sugar level drops and appetite increases. So they reach for a snack. Usually this is a high carbohydrate snack or beverage. This again raises insulin. Some have recommended "grazing." This means eating many small meals throughout the day. Obviously this will maintain a steady flow of carbohydrates into the bloodstream, with the resulting elevation in insulin level.  

As an aside - It is highly doubtful that our ancestors evolved during times when high-carbohydrate foods were available at all times. In fact it is doubtful that hunter-gatherers had constant access to ANY foods. So the idea that eating all the time (even when driving) makes any sense is ridiculous.

Anyway, because elevated insulin causes weight gain, the person gains weight. Homeostasis applies to cells specifically, just as it does to the body in general. What does this mean? As fat cells get increasingly full of stored fat they become increasingly resistant to additional storage. Because insulin is the hormone telling them to store more fat they become insulin resistant. This happens throughout our body. The body responds by further increasing the insulin secretion until blood sugar drops into the desired range. This cycle continues over and over. Insulin resistance worsens over time. The ever higher insulin level prevents mobilization of body fat for energy and increases appetite, intensifying the problem. 

THIS CYCLE MUST BE BROKEN TO ACHIEVE WEIGHT LOSS. 

Carbohydrates are the most powerful driver of insulin. Protein also causes insulin release, but significantly less than carbohydrates. Dietary fat causes minimal insulin release. Usually, insulin resistance improves dramatically when carbohydrates are restricted. 

If you struggle with a low carbohydrate diet, if you feel hungry all the time in spite of eating dietary fat, if weight loss stalls, you very likely have significant insulin resistance. 

WHAT TO DO?

1- Make sure you are really not eating carbohydrates. They are snuck into everything- especially processed foods and in restaurants.  Read labels. Even better- make your own food. Stick with non-starchy vegetables and meats and dietary fat. 

2- Don't eat tons of protein. 

3- Avoid artificial sweeteners. Although they contain minimal to no calories, studies have shown they cause insulin release. That diet soda will actually make you fat. Avoiding sweet tasting foods will gradually reduce their desirability. 

4- The most powerful way to break through insulin resistance is with fasting. Our pancreas secretes insulin as we prepare to take a bite of food. Additional insulin is released during chewing and swallowing  in anticipation of the subsequent blood sugar elevation. Therefore, completely avoiding food will minimize insulin levels. Back to homeostasis. As our blood insulin level drops, our cells release stored body fat for energy. As we maintain a low insulin level by extending the fast, our cells will become more sensitive to insulin again. This can actually reverse insulin resistance. Although fasting initially sounds crazy, it turns out to be fairly easy. 

Soon after beginning to eat a low-carbohydrate, high-fat diet I found myself eating because it was "time to eat" not necessarily because I was hungry. Without doing much research at the time, I decided to skip a meal and see what happened. Amazingly, I found that when I skipped lunch I made it all the way to dinner. I did not instantly lose all my muscle mass, nor did I experience lack of energy. Then I skipped breakfast and lunch. This felt strange to me as it was contrary to the often recited recommendation to eat many small meals throughout the day. I had repeatedly heard that skipping breakfast increases the likelihood of developing obesity and diabetes. Loss of lean muscle mass was also commonly cited. It seemed like I was embarking on exactly the wrong path.

And yet it made no sense to me to eat when I was not hungry. Especially when I felt better during the fasted state. It seemed to me I had stumbled upon yet another myth of modern nutrition- that humans need to be eating constantly. Thinking back to a time before industrial food and agriculture companies, our ancestors were hunter gatherers and probably experienced widely varying caloric intakes over time. Perhaps intermittent fasting was actually the normal situation back then. Individuals that thrived under such conditions would have been more likely to pass on their genes to future generations. In the modern day, with abundant low nutrient density foods omnipresent, those genes that led to survival back then may  have become counterproductive. Perhaps if we mimic ancestral conditions by varying food intake as opposed to continually flooding our bodies with food we also will thrive. 

There have been many studies on this topic and most show intermittent fasting is likely to be quite good for us. Let's look at some of the major findings:

Weight loss
The concept of the yo-yo diet is well known. Diets, in the traditional sense are temporary, unpleasant restrictions in food quantity that result in some amount of weight loss. Once the diet ends, most people regain all the weight they lost and usually a little bit more. Over time they end up gaining weight. This is not metabolically healthy. Studies investigating intermittent fasting have shown reductions in both body weight and body fat while maintaining or even adding lean body mass. 

Additionally, people tend to find intermittent fasting much more sustainable than simple caloric restriction. This is probably because intermittent fasting may induce a temporary state of nutritional ketosis, especially when done as part of a low-carbohydrate, high-fat diet. Ketosis fuels your body with fat metabolites (ketone bodies) and thus suppresses hunger and provides abundant energy during the fast.

Insulin Sensitivity
Studies consistently show improved insulin sensitivity as a result of intermittent fasting protocols. Remember our discussion of increased baseline insulin secretion that results from exposure to a high-carbohydrate diet? Intermittent fasting reverses this. When not exposed to carbohydrates and proteins for a period of time, the pancreas is able to reduce insulin production and our cells then are exposed to lower insulin levels. The cells in turn will up-regulate their insulin receptors. And just like that, insulin sensitivity improves. It makes sense and studies confirm this. 

Cardio-protective
Heart attack animal models have shown less heart muscle damage after myocardial infarction (heart attack) if the animal was on an intermittent fasting protocol. Additionally, lipid profiles improve with  intermittent fasting. Increased HDL(good cholesterol), decreased triglycerides and decreased total cholesterol were seen in multiple studies. Reduction in systolic and diastolic blood pressure that results from intermittent fasting places a decreased load on the heart. Lastly, intermittent fasting resulted in markedly improved survival in a congestive heart failure animal model. It should be noted that lipid profiles do not necessarily improve in patients with familial hypercholesterolemia, and this technique should probably be avoided in this unique situation.

Neuro-Protective
Intermittent fasting has been found to reduce neuron damage in animal stroke models,  reduce spinal cord demyelination in multiple sclerosis animal models, prevent age-related impairment of brain function, increase neuronal resistance to injury, and may even protect neurons against the degenerative changes that cause Alzheimer's dementia.

Mental Health
Patients commonly report feeling reduced anxiety and improved ability to focus during a fast. Studies report reduced impulsivity, decreased anger, decreased confusion and improved vigor while on an intermittent fasting protocol. 

Immune System Support
Mice adapted to intermittent fasting showed an improved immune response to, and faster clearance of a Salmonella infection compared to those allowed to eat freely.  

Anti-inflammatory
Since we have been discussing a variety of protective effects associated with intermittent fasting, it comes as no surprise to hear that intermittent fasting is associated with reduced inflammatory markers in blood tests. 

​Anti-cancer
Caloric restriction and ketogenic diets have been show to be effective against some cancers in animal models. Dormant cancer cells are dependent on anaerobic glucose metabolism. These cells can result in cancer relapses. Since blood glucose levels can be decreased by up to 40% during fasting, it is felt that fasting may cause these dormant cells to die. Early prostate cancer animal studies show a trend toward improved survival in the intermittent fasting group. 

Radiation Protective
Mice that had adapted to intermittent fasting suffered less damage when exposed to gamma radiation. This protective effect was lost when the mice were allowed to eat freely. 


In addition to the potential health benefits, there are some more immediate, practical benefits of intermittent fasting as well:

It is free. I recommend consuming grass-fed, grass-finished meats, wild caught fish, and organic vegetables whenever possible. These foods are more expensive than the standard versions. Skipping meals helps to offset this expense. 

It is fast. You will not have to spend any time preparing breakfast or lunch on fasting days. 

Improved productivity. The lunch hour is now free-time during which other things can be done. 



How to do it?

1- Train your body to burn body fat for energy. This will greatly facilitate transitioning into intermittent fasting. In my case it happened automatically. Read my earlier blog postings for details. Start with carbohydrate restriction, make sure you are eating the proper amount of protein, and don't be afraid to eat fat. You must eat fat to burn fat. 

2- Your body will adapt to preferentially burning fat over a period of weeks. During the first two weeks you may feel a bit strange, you will likely lose 10 or more pounds. Stay well hydrated and eat healthy fats when hungry. 

3- Within 6 weeks of beginning a low carbohydrate diet many people easily and automatically transition into intermittent fasting. If you would like to try this - simply skip breakfast and lunch and eat a proper dinner. ​Stay well hydrated throughout the day. Black coffee and tea can be consumed during the fast. To sleep properly, stop consuming caffeine by 2PM. Water should be consumed throughout the day. 

4- It appears the beneficial effects of fasting require at least 12 hours without eating, and benefits increase with longer fasting periods. Although fasting can safely be extended beyond 24 hours, most people do not need to. Because eating is also a social event, I prefer fasting from after dinner until dinner the next day. This way I can sit down and enjoy eating with my family, and it provides me an easily sustainable 18-20 hour fasting period. Sleeping through a large portion of this fasting period makes this even easier. 

5- Bulletproof coffee. This is a "biohack" developed by Dave Asprey. Adding some butter and coconut oil or MCT oil to black coffee and then blending, it creates tiny droplets of fat suspended in the coffee. Try a teaspoon of each to start and adjust as needed.  At first this might seem like it would be unpalatable, but I encourage you to try it with an open mind. It not only tastes much better than expected, it has an excellent mouth feel, and makes you feel good. It helps your body to produce ketone bodies (especially if MCT oil is used). It takes advantage of how our body metabolizes dietary fat. When we consume pure fat while in a fasted state, our body will continue to function as if it is fasting. There is no insulin response.  Dave Asprey markets a more refined version of MCT oil he calls Brain Octane Oil. It includes only the 8 chain fatty acids which produce ketone bodies most efficiently. I started intermittent fasting initially drinking bulletproof coffee for breakfast and lunch. I gradually transitioned back to black coffee as my body adjusted and seemed to mobilize stored energy better. 

6- When breaking the fast, do not calorie restrict. Eat a proper meal at a proper pace. A large salad, some high quality meat or fish and a small serving of white rice or sweet potato. Fill your plate and enjoy your meal. 


References:
Wahl D, Cogger VC, Solon-Biet SM, Waern RV, Gokarn R, Pulpitel T, Cabo Rd, Mattson MP, Raubenheimer D, Simpson SJ, Le Couteur DG. Nutritional strategies to optimise cognitive function in the aging brain. Ageing Res Rev. 2016 Nov;31:80-92. doi: 10.1016/j.arr.2016.06.006. Epub 2016 Jun 26. Review. PubMed PMID: 27355990; PubMed Central PMCID: PMC5035589.

Dashti HS, Mogensen KM. Recommending Small, Frequent Meals in the Clinical Care of Adults: A Review of the Evidence and Important Considerations. Nutr Clin Pract. 2016 Sep 1. pii: 0884533616662995. [Epub ahead of print] Review. PubMed PMID: 27589258.

Tinsley GM, Forsse JS, Butler NK, Paoli A, Bane AA, La Bounty PM, Morgan GB, Grandjean PW. Time-restricted feeding in young men performing resistance training: A randomized controlled trial. Eur J Sport Sci. 2016 Aug 22:1-8. [Epub ahead of print] PubMed PMID: 27550719.

Jarvie BC, King CM, Hughes AR, Dicken MS, Dennison CS, Hentges ST. Caloric restriction selectively reduces the GABAergic phenotype of mouse hypothalamic proopiomelanocortin neurons. J Physiol. 2016 Aug 17. doi: 10.1113/JP273020. [Epub ahead of print] PubMed PMID: 27531218.
Gow ML, Garnett SP, Baur LA, Lister NB. The Effectiveness of Different Diet Strategies to Reduce Type 2 Diabetes Risk in Youth.Nutrients. 2016 Aug 9;8(8). pii: E486. doi: 10.3390/nu8080486. Review. PubMed PMID: 27517953; PubMed Central PMCID: PMC4997399.

Arciero PJ, Edmonds R, He F, Ward E, Gumpricht E, Mohr A, Ormsbee MJ, Astrup A. Protein-Pacing Caloric-Restriction Enhances Body Composition Similarly in Obese Men and Women during Weight Loss and Sustains Efficacy during Long-Term Weight Maintenance. Nutrients. 2016 Jul 30;8(8). pii: E476. doi: 10.3390/nu8080476. PubMed PMID: 27483317; PubMed Central PMCID: PMC4997389.

Varady KA. Impact of intermittent fasting on glucose homeostasis. Curr Opin Clin Nutr Metab Care. 2016 Jul;19(4):300-2. doi: 10.1097/MCO.0000000000000291. PubMed PMID: 27137896.

Harvie MN, Howell T. Could Intermittent Energy Restriction and Intermittent Fasting Reduce Rates of Cancer in Obese, Overweight, and Normal-Weight Subjects? A Summary of Evidence. Adv Nutr. 2016 Jul 15;7(4):690-705. doi: 10.3945/an.115.011767. Print 2016 Jul. Review. PubMed PMID: 27422504; PubMed Central PMCID: PMC4942870.

Longo VD, Panda S. Fasting, Circadian Rhythms, and Time-Restricted Feeding in Healthy Lifespan. Cell Metab. 2016 Jun 14;23(6):1048-59. doi: 10.1016/j.cmet.2016.06.001. Review. PubMed PMID: 27304506.

Joslin PM, Bell RK, Swoap SJ. Obese mice on a high-fat alternate-day fasting regimen lose weight and improve glucose tolerance.J Anim Physiol Anim Nutr (Berl). 2016 Jun 8. doi: 10.1111/jpn.12546. [Epub ahead of print] PubMed PMID: 27273295.

Belaïch R, Boujraf S, Benzagmout M, Magoul R, Maaroufi M, Tizniti S. Implications of oxidative stress in the brain plasticity originated by fasting: a BOLD-fMRI study. Nutr Neurosci. 2016 Jun 8:1-8. [Epub ahead of print] PubMed PMID: 27276372.

Razeghi Jahromi S, Ghaemi A, Alizadeh A, Sabetghadam F, Moradi Tabriz H, Togha M. Effects of Intermittent Fasting on Experimental Autoimune Encephalomyelitis in C57BL/6 Mice. Iran J Allergy Asthma Immunol. 2016 Jun;15(3):212-9. PubMed PMID: 27424136.

Nair PM, Khawale PG. Role of therapeutic fasting in women's health: An overview. J Midlife Health. 2016 Apr-Jun;7(2):61-4. doi: 10.4103/0976-7800.185325. Review. PubMed PMID: 27499591; PubMed Central PMCID: PMC4960941.
 
Hou L, Wang D, Chen D, Liu Y, Zhang Y, Cheng H, Xu C, Sun N, McDermott J, Mair WB, Han JD. A Systems Approach to Reverse Engineer Lifespan Extension by Dietary Restriction. Cell Metab. 2016 Mar 8;23(3):529-40. doi: 10.1016/j.cmet.2016.02.002. PubMed PMID: 26959186.

Sibille KT, Bartsch F, Reddy D, Fillingim RB, Keil A. Increasing Neuroplasticity to Bolster Chronic Pain Treatment: A Role for Intermittent Fasting and Glucose Administration? J Pain. 2016 Mar;17(3):275-81. doi: 10.1016/j.jpain.2015.11.002. Epub 2016 Feb 2. PubMed PMID: 26848123; PubMed Central PMCID: PMC4824292.

Chamari K, Briki W, Farooq A, Patrick T, Belfekih T, Herrera CP. Impact of Ramadan intermittent fasting on cognitive function in trained cyclists: a pilot study. Biol Sport. 2016 Mar;33(1):49-56. doi: 10.5604/20831862.1185888. Epub 2015 Dec 30. PubMed PMID: 26985134; PubMed Central PMCID: PMC4786586.

Gotthardt JD, Verpeut JL, Yeomans BL, Yang JA, Yasrebi A, Roepke TA, Bello NT. Intermittent Fasting Promotes Fat Loss With Lean Mass Retention, Increased Hypothalamic Norepinephrine Content, and Increased Neuropeptide Y Gene Expression in Diet-Induced Obese Male Mice. Endocrinology. 2016 Feb;157(2):679-91. doi: 10.1210/en.2015-1622. Epub 2015 Dec 14. PubMed PMID: 26653760; PubMed Central PMCID: PMC4733124.

Campos-Rodríguez R, Godínez-Victoria M, Reyna-Garfias H, Arciniega-Martínez IM, Reséndiz-Albor AA, Abarca-Rojano E, Cruz-Hernández TR, Drago-Serrano ME. Intermittent fasting favored the resolution of Salmonella typhimurium infection in middle-aged BALB/c mice. Age (Dordr). 2016 Feb;38(1):13. doi: 10.1007/s11357-016-9876-3. Epub 2016 Jan 21. PubMed PMID: 26798034; PubMed Central PMCID: PMC5005893.
 
Cherif A, Roelands B, Meeusen R, Chamari K. Effects of Intermittent Fasting, Caloric Restriction, and Ramadan Intermittent Fasting on Cognitive Performance at Rest and During Exercise in Adults. Sports Med. 2016 Jan;46(1):35-47. doi: 10.1007/s40279-015-0408-6. Review. PubMed PMID: 26438184.

Seimon RV, Shi YC, Slack K, Lee K, Fernando HA, Nguyen AD, Zhang L, Lin S, Enriquez RF, Lau J, Herzog H, Sainsbury A. Intermittent Moderate Energy Restriction Improves Weight Loss Efficiency in Diet-Induced Obese Mice. PLoS One. 2016 Jan 19;11(1):e0145157. doi: 10.1371/journal.pone.0145157. eCollection 2016. PubMed PMID: 26784324; PubMed Central PMCID: PMC4718562.
 
BaHammam AS, Pandi-Perumal SR, Alzoghaibi MA. The effect of Ramadan intermittent fasting on lipid peroxidation in healthy young men while controlling for diet and sleep: A pilot study. Ann Thorac Med. 2016 Jan-Mar;11(1):43-8. doi: 10.4103/1817-1737.172296. PubMed PMID: 26933456; PubMed Central PMCID: PMC4748614.

Zarrouk N, Hammouda O, Latiri I, Adala H, Bouhlel E, Rebai H, Dogui M. Ramadan fasting does not adversely affect neuromuscular performances and reaction times in trained karate athletes. J Int Soc Sports Nutr. 2016 Apr 19;13:18. doi: 10.1186/s12970-016-0130-2. eCollection 2016. PubMed PMID: 27099568; PubMed Central PMCID: PMC4837563.

Zuo L, He F, Tinsley GM, Pannell BK, Ward E, Arciero PJ. Comparison of High-Protein, Intermittent Fasting Low-Calorie Diet and Heart Healthy Diet for Vascular Health of the Obese. Front Physiol. 2016 Aug 29;7:350. doi: 10.3389/fphys.2016.00350. eCollection 2016. PubMed PMID: 27621707; PubMed Central PMCID: PMC5002412.

Singh R, Manchanda S, Kaur T, Kumar S, Lakhanpal D, Lakhman SS, Kaur G. Middle age onset short-term intermittent fasting dietary restriction prevents brain function impairments in male Wistar rats. Biogerontology. 2015 Dec;16(6):775-88. doi: 10.1007/s10522-015-9603-y. Epub 2015 Aug 30. PubMed PMID: 26318578.

Tinsley GM, La Bounty PM. Effects of intermittent fasting on body composition and clinical health markers in humans. Nutr Rev. 2015 Oct;73(10):661-74. doi: 10.1093/nutrit/nuv041. Epub 2015 Sep 15. Review. PubMed PMID: 26374764.

Jane L, Atkinson G, Jaime V, Hamilton S, Waller G, Harrison S. Intermittent fasting interventions for the treatment of overweight and obesity in adults aged 18 years and over: a systematic review protocol. JBI Database System Rev Implement Rep. 2015 Oct;13(10):60-8. doi: 10.11124/jbisrir-2015-2363. PubMed PMID: 26571283.

Patterson RE, Laughlin GA, LaCroix AZ, Hartman SJ, Natarajan L, Senger CM, Martínez ME, Villaseñor A, Sears DD, Marinac CR, Gallo LC. Intermittent Fasting and Human Metabolic Health. J Acad Nutr Diet. 2015 Aug;115(8):1203-12. doi: 10.1016/j.jand.2015.02.018. Epub 2015 Apr 6. PubMed PMID: 25857868; PubMed Central PMCID: PMC4516560.

Horne BD, Muhlestein JB, Anderson JL. Health effects of intermittent fasting: hormesis or harm? A systematic review. Am J Clin Nutr. 2015 Aug;102(2):464-70. doi: 10.3945/ajcn.115.109553. Epub 2015 Jul 1. Review. PubMed PMID: 26135345.

Carey SK, Conchin S, Bloomfield-Stone S. A qualitative study into the impact of fasting within a large tertiary hospital in Australia--the patients' perspective. J Clin Nurs. 2015 Jul;24(13-14):1946-54. doi: 10.1111/jocn.12847. Epub 2015 May 11. PubMed PMID: 25959390.

Johnstone A. Fasting for weight loss: an effective strategy or latest dieting trend? Int J Obes (Lond). 2015 May;39(5):727-33. doi: 10.1038/ijo.2014.214. Epub 2014 Dec 26. Review. PubMed PMID: 25540982.
 
Baumeier C, Kaiser D, Heeren J, Scheja L, John C, Weise C, Eravci M, Lagerpusch M, Schulze G, Joost HG, Schwenk RW, Schürmann A. Caloric restriction and intermittent fasting alter hepatic lipid droplet proteome and diacylglycerol species and prevent diabetes in NZO mice. Biochim Biophys Acta. 2015 May;1851(5):566-76. doi: 10.1016/j.bbalip.2015.01.013. Epub 2015 Jan 31. PubMed PMID: 25645620.

Wegman MP, Guo MH, Bennion DM, Shankar MN, Chrzanowski SM, Goldberg LA, Xu J, Williams TA, Lu X, Hsu SI, Anton SD, Leeuwenburgh C, Brantly ML. Practicality of intermittent fasting in humans and its effect on oxidative stress and genes related to aging and metabolism. Rejuvenation Res. 2015 Apr;18(2):162-72. doi: 10.1089/rej.2014.1624. PubMed PMID: 25546413; PubMed Central PMCID: PMC4403246.

Samad F, Qazi F, Pervaiz MB, Kella DK, Mansoor M, Osmani BZ, Mir F, Kadir MM. EFFECTS OF RAMADAN FASTING ON BLOOD PRESSURE IN NORMOTENSIVE MALES. J Ayub Med Coll Abbottabad. 2015 Apr-Jun;27(2):338-42. PubMed PMID: 26411111.

Bemben DA, Sharma-Ghimire P, Chen Z, Kim E, Kim D, Bemben MG. Effects of whole-body vibration on acute bone turnover marker responses to resistance exercise in young men. J Musculoskelet Neuronal Interact. 2015 Mar;15(1):23-31. PubMed PMID: 25730649.
 
Lankelma J, Kooi B, Krab K, Dorsman JC, Joenje H, Westerhoff HV. A reason for intermittent fasting to suppress the awakening of dormant breast tumors. Biosystems. 2015 Jan;127:1-6. doi: 10.1016/j.biosystems.2014.11.001. Epub 2014 Nov 4. PubMed PMID: 25448890.

Chausse B, Vieira-Lara MA, Sanchez AB, Medeiros MH, Kowaltowski AJ. Intermittent fasting results in tissue-specific changes in bioenergetics and redox state. PLoS One. 2015 Mar 6;10(3):e0120413. doi: 10.1371/journal.pone.0120413. eCollection 2015. PubMed PMID: 25749501; PubMed Central PMCID: PMC4352038.

Godar RJ, Ma X, Liu H, Murphy JT, Weinheimer CJ, Kovacs A, Crosby SD, Saftig P, Diwan A. Repetitive stimulation of autophagy-lysosome machinery by intermittent fasting preconditions the myocardium to ischemia-reperfusion injury. Autophagy. 2015;11(9):1537-60. doi: 10.1080/15548627.2015.1063768. PubMed PMID: 26103523; PubMed Central PMCID: PMC4590628.

Barnosky AR, Hoddy KK, Unterman TG, Varady KA. Intermittent fasting vs daily calorie restriction for type 2 diabetes prevention: a review of human findings. Transl Res. 2014 Oct;164(4):302-11. doi: 10.1016/j.trsl.2014.05.013. Epub 2014 Jun 12. Review. PubMed PMID: 24993615.

Fann DY, Santro T, Manzanero S, Widiapradja A, Cheng YL, Lee SY, Chunduri P, Jo DG, Stranahan AM, Mattson MP, Arumugam TV. Intermittent fasting attenuates inflammasome activity in ischemic stroke. Exp Neurol. 2014 Jul;257:114-9. doi: 10.1016/j.expneurol.2014.04.017. Epub 2014 May 5. PubMed PMID: 24805069.
: 
Aly SM. Role of intermittent fasting on improving health and reducing diseases. Int J Health Sci (Qassim). 2014 Jul;8(3):V-VI. PubMed PMID: 25505868; PubMed Central PMCID: PMC4257368.

Vasconcelos AR, Yshii LM, Viel TA, Buck HS, Mattson MP, Scavone C, Kawamoto EM. Intermittent fasting attenuates lipopolysaccharide-induced neuroinflammation and memory impairment. J Neuroinflammation. 2014 May 6;11:85. doi: 10.1186/1742-2094-11-85. PubMed PMID: 24886300; PubMed Central PMCID: PMC4041059.

Manzanero S, Erion JR, Santro T, Steyn FJ, Chen C, Arumugam TV, Stranahan AM. Intermittent fasting attenuates increases in neurogenesis after ischemia and reperfusion and improves recovery. J Cereb Blood Flow Metab. 2014 May;34(5):897-905. doi: 10.1038/jcbfm.2014.36. Epub 2014 Feb 19. PubMed PMID: 24549184; PubMed Central PMCID: PMC4013772.

Godínez-Victoria M, Campos-Rodriguez R, Rivera-Aguilar V, Lara-Padilla E, Pacheco-Yepez J, Jarillo-Luna RA, Drago-Serrano ME. Intermittent fasting promotes bacterial clearance and intestinal IgA production in Salmonella typhimurium-infected mice. Scand J Immunol. 2014 May;79(5):315-24. doi: 10.1111/sji.12163. PubMed PMID: 24612255.

Dorighello GG, Rovani JC, Luhman CJ, Paim BA, Raposo HF, Vercesi AE, Oliveira HC. Food restriction by intermittent fasting induces diabetes and obesity and aggravates spontaneous atherosclerosis development in hypercholesterolaemic mice. Br J Nutr. 2014 Mar 28;111(6):979-86. doi: 10.1017/S0007114513003383. Epub 2013 Nov 1. PubMed PMID: 24176004.

Westbrook R, Bonkowski MS, Arum O, Strader AD, Bartke A. Metabolic alterations due to caloric restriction and every other day feeding in normal and growth hormone receptor knockout mice. J Gerontol A Biol Sci Med Sci. 2014 Jan;69(1):25-33. doi: 10.1093/gerona/glt080. Epub 2013 Jul 5. PubMed PMID: 23833202; PubMed Central PMCID: PMC3859362.

Alzoghaibi MA, Pandi-Perumal SR, Sharif MM, BaHammam AS. Diurnal intermittent fasting during Ramadan: the effects on leptin and ghrelin levels. PLoS One. 2014 Mar 17;9(3):e92214. doi: 10.1371/journal.pone.0092214. eCollection 2014. PubMed PMID: 24637892; PubMed Central PMCID: PMC3956913.
 
Lv M, Zhu X, Wang H, Wang F, Guan W. Roles of caloric restriction, ketogenic diet and intermittent fasting during initiation, progression and metastasis of cancer in animal models: a systematic review and meta-analysis. PLoS One. 2014 Dec 11;9(12):e115147. doi: 10.1371/journal.pone.0115147. eCollection 2014. PubMed PMID: 25502434; PubMed Central PMCID: PMC4263749.

Teng NI, Shahar S, Rajab NF, Manaf ZA, Johari MH, Ngah WZ. Improvement of metabolic parameters in healthy older adult men following a fasting calorie restriction intervention. Aging Male. 2013 Dec;16(4):177-83. doi: 10.3109/13685538.2013.832191. Epub 2013 Sep 17. PubMed PMID: 24044618.

Collier R. Intermittent fasting: the science of going without. CMAJ. 2013 Jun 11;185(9):E363-4. doi: 10.1503/cmaj.109-4451. Epub 2013 Apr 8. PubMed PMID: 23569168; PubMed Central PMCID: PMC3680567.

Pilon B. Intermittent fasting: five quick questions with fasting expert Brad Pilon. Interview by Roger Collier. CMAJ. 2013 Jun 11;185(9):E362. doi: 10.1503/cmaj.109-4438. Epub 2013 Apr 15. PubMed PMID: 23589435; PubMed Central PMCID: PMC3680566.

Collier R. Intermittent fasting: the next big weight loss fad. CMAJ. 2013 May 14;185(8):E321-2. doi: 10.1503/cmaj.109-4437. Epub 2013 Mar 25. PubMed PMID: 23529969; PubMed Central PMCID: PMC3652955.
: 
Azevedo FR, Ikeoka D, Caramelli B. Effects of intermittent fasting on metabolism in men. Rev Assoc Med Bras (1992). 2013 Mar-Apr;59(2):167-73. doi: 10.1016/j.ramb.2012.09.003. Review. PubMed PMID: 23582559.

Li L, Wang Z, Zuo Z. Chronic intermittent fasting improves cognitive functions and brain structures in mice. PLoS One. 2013 Jun 3;8(6):e66069. doi: 10.1371/journal.pone.0066069. Print 2013. PubMed PMID: 23755298; PubMed Central PMCID: PMC3670843.

Hussin NM, Shahar S, Teng NI, Ngah WZ, Das SK. Efficacy of fasting and calorie restriction (FCR) on mood and depression among ageing men. J Nutr Health Aging. 2013;17(8):674-80. doi: 10.1007/s12603-013-0344-9. PubMed PMID: 24097021.

Hammouda O, Chtourou H, Aloui A, Chahed H, Kallel C, Miled A, Chamari K, Chaouachi A, Souissi N. Concomitant effects of Ramadan fasting and time-of-day on apolipoprotein AI, B, Lp-a and homocysteine responses during aerobic exercise in Tunisian soccer players. PLoS One. 2013 Nov 11;8(11):e79873. doi: 10.1371/journal.pone.0079873. eCollection 2013. PubMed PMID: 24244572; PubMed Central PMCID: PMC3823586.

Faris MA, Kacimi S, Al-Kurd RA, Fararjeh MA, Bustanji YK, Mohammad MK, Salem ML. Intermittent fasting during Ramadan attenuates proinflammatory cytokines and immune cells in healthy subjects. Nutr Res. 2012 Dec;32(12):947-55. doi: 10.1016/j.nutres.2012.06.021. Epub 2012 Oct 4. PubMed PMID: 23244540.

Kroeger CM, Klempel MC, Bhutani S, Trepanowski JF, Tangney CC, Varady KA. Improvement in coronary heart disease risk factors during an intermittent fasting/calorie restriction regimen: Relationship to adipokine modulations. Nutr Metab (Lond). 2012 Oct 31;9(1):98. doi: 10.1186/1743-7075-9-98. PubMed PMID: 23113919; PubMed Central PMCID: PMC3514278.

Singh R, Lakhanpal D, Kumar S, Sharma S, Kataria H, Kaur M, Kaur G. Late-onset intermittent fasting dietary restriction as a potential intervention to retard age-associated brain function impairments in male rats. Age (Dordr). 2012 Aug;34(4):917-33. doi: 10.1007/s11357-011-9289-2. Epub 2011 Aug 23. PubMed PMID: 21861096; PubMed Central PMCID: PMC3682068.

Arguin H, Dionne IJ, Sénéchal M, Bouchard DR, Carpentier AC, Ardilouze JL, Tremblay A, Leblanc C, Brochu M. Short- and long-term effects of continuous versus intermittent restrictive diet approaches on body composition and the metabolic profile in overweight and obese postmenopausal women: a pilot study. Menopause. 2012 Aug;19(8):870-6. PubMed PMID: 22735163.

Karbowska J, Kochan Z. Intermittent fasting up-regulates Fsp27/Cidec gene expression in white adipose tissue. Nutrition. 2012 Mar;28(3):294-9. doi: 10.1016/j.nut.2011.06.009. Epub 2011 Oct 12. PubMed PMID: 21996045.

Belkacemi L, Selselet-Attou G, Hupkens E, Nguidjoe E, Louchami K, Sener A, Malaisse WJ. Intermittent fasting modulation of the diabetic syndrome in streptozotocin-injected rats. Int J Endocrinol. 2012;2012:962012. doi: 10.1155/2012/962012. Epub 2012 Jan 12. PubMed PMID: 22291702; PubMed Central PMCID: PMC3265126.

Faris MA, Hussein RN, Al-Kurd RA, Al-Fararjeh MA, Bustanji YK, Mohammad MK. Impact of ramadan intermittent fasting on oxidative stress measured by urinary 15-f(2t)-isoprostane. J Nutr Metab. 2012;2012:802924. doi: 10.1155/2012/802924. Epub 2012 Oct 22. PubMed PMID: 23150812; PubMed Central PMCID: PMC3485525.
 
Thompson HJ, McTiernan A. Weight cycling and cancer: weighing the evidence of intermittent caloric restriction and cancer risk.Cancer Prev Res (Phila). 2011 Nov;4(11):1736-42. doi: 10.1158/1940-6207.CAPR-11-0133. Epub 2011 Oct 7. Review. PubMed PMID: 21982873; PubMed Central PMCID: PMC3208747.

Razzak RL, Abu-Hozaifa BM, Bamosa AO, Ali NM. Assessment of enhanced endothelium-dependent vasodilation by intermittent fasting in Wistar albino rats. Indian J Physiol Pharmacol. 2011 Oct-Dec;55(4):336-42. PubMed PMID: 23362726.

Harvie MN, Pegington M, Mattson MP, Frystyk J, Dillon B, Evans G, Cuzick J, Jebb SA, Martin B, Cutler RG, Son TG, Maudsley S, Carlson OD, Egan JM, Flyvbjerg A, Howell A. The effects of intermittent or continuous energy restriction on weight loss and metabolic disease risk markers: a randomized trial in young overweight women. Int J Obes (Lond). 2011 May;35(5):714-27. doi: 10.1038/ijo.2010.171. Epub 2010 Oct 5. PubMed PMID: 20921964; PubMed Central PMCID: PMC3017674.

Lu J, E L, Wang W, Frontera J, Zhu H, Wang WT, Lee P, Choi IY, Brooks WM, Burns JM, Aires D, Swerdlow RH. Alternate day fasting impacts the brain insulin-signaling pathway of young adult male C57BL/6 mice. J Neurochem. 2011 Apr;117(1):154-63. doi: 10.1111/j.1471-4159.2011.07184.x. Epub 2011 Feb 9. PubMed PMID: 21244426; PubMed Central PMCID: PMC3055925.

Jeong MA, Plunet W, Streijger F, Lee JH, Plemel JR, Park S, Lam CK, Liu J, Tetzlaff W. Intermittent fasting improves functional recovery after rat thoracic contusion spinal cord injury. J Neurotrauma. 2011 Mar;28(3):479-92. doi: 10.1089/neu.2010.1609. PubMed PMID: 21219083; PubMed Central PMCID: PMC3119327.

Belkacemi L, Selselet-Attou G, Bulur N, Louchami K, Sener A, Malaisse WJ. Intermittent fasting modulation of the diabetic syndrome in sand rats. III. Post-mortem investigations. Int J Mol Med. 2011 Jan;27(1):95-102. doi: 10.3892/ijmm.2010.556. Epub 2010 Nov 10. PubMed PMID: 21069262.

Thomas JA 2nd, Antonelli JA, Lloyd JC, Masko EM, Poulton SH, Phillips TE, Pollak M, Freedland SJ. Effect of intermittent fasting on prostate cancer tumor growth in a mouse model. Prostate Cancer Prostatic Dis. 2010 Dec;13(4):350-5. doi: 10.1038/pcan.2010.24. Epub 2010 Aug 24. PubMed PMID: 20733612.

Belkacemi L, Selselet-Attou G, Louchami K, Sener A, Malaisse WJ. Intermittent fasting modulation of the diabetic syndrome in sand rats. II. In vivo investigations. Int J Mol Med. 2010 Nov;26(5):759-65. PubMed PMID: 20878099.

Tajes M, Gutierrez-Cuesta J, Folch J, Ortuño-Sahagun D, Verdaguer E, Jiménez A, Junyent F, Lau A, Camins A, Pallàs M. Neuroprotective role of intermittent fasting in senescence-accelerated mice P8 (SAMP8). Exp Gerontol. 2010 Sep;45(9):702-10. doi: 10.1016/j.exger.2010.04.010. Epub 2010 May 9. PubMed PMID: 20460146.

Buschemeyer WC 3rd, Klink JC, Mavropoulos JC, Poulton SH, Demark-Wahnefried W, Hursting SD, Cohen P, Hwang D, Johnson TL, Freedland SJ. Effect of intermittent fasting with or without caloric restriction on prostate cancer growth and survival in SCID mice. Prostate. 2010 Jul 1;70(10):1037-43. doi: 10.1002/pros.21136. PubMed PMID: 20166128.

Wan R, Ahmet I, Brown M, Cheng A, Kamimura N, Talan M, Mattson MP. Cardioprotective effect of intermittent fasting is associated with an elevation of adiponectin levels in rats. J Nutr Biochem. 2010 May;21(5):413-7. doi: 10.1016/j.jnutbio.2009.01.020. Epub 2009 May 7. PubMed PMID: 19423320; PubMed Central PMCID: PMC2854256.

Katare RG, Kakinuma Y, Arikawa M, Yamasaki F, Sato T. Chronic intermittent fasting improves the survival following large myocardial ischemia by activation of BDNF/VEGF/PI3K signaling pathway. J Mol Cell Cardiol. 2009 Mar;46(3):405-12. doi: 10.1016/j.yjmcc.2008.10.027. Epub 2008 Nov 12. PubMed PMID: 19059263.

Salim S, Farooq N, Priyamvada S, Asghar M, Khundmiri SJ, Khan S, Khan F, Yusufi AN. Influence of Ramadan-type fasting on carbohydrate metabolism, brush border membrane enzymes and phosphate transport in rat kidney used as a model. Br J Nutr. 2007 Nov;98(5):984-90. Epub 2007 Sep 3. PubMed PMID: 17764602.

Donato J Jr, Pedrosa RG, de Araújo JA Jr, Pires IS, Tirapegui J. Effects of leucine and phenylalanine supplementation during intermittent periods of food restriction and refeeding in adult rats. Life Sci. 2007 Jun 13;81(1):31-9. Epub 2007 Apr 24. PubMed PMID: 17512018.

Halagappa VK, Guo Z, Pearson M, Matsuoka Y, Cutler RG, Laferla FM, Mattson MP. Intermittent fasting and caloric restriction ameliorate age-related behavioral deficits in the triple-transgenic mouse model of Alzheimer's disease. Neurobiol Dis. 2007 Apr;26(1):212-20. Epub 2007 Jan 13. PubMed PMID: 17306982.

Tikoo K, Tripathi DN, Kabra DG, Sharma V, Gaikwad AB. Intermittent fasting prevents the progression of type I diabetic nephropathy in rats and changes the expression of Sir2 and p53. FEBS Lett. 2007 Mar 6;581(5):1071-8. Epub 2007 Feb 14. PubMed PMID: 17316625.

Martin B, Mattson MP, Maudsley S. Caloric restriction and intermittent fasting: two potential diets for successful brain aging. Ageing Res Rev. 2006 Aug;5(3):332-53. Epub 2006 Aug 8. Review. PubMed PMID: 16899414; PubMed Central PMCID: PMC2622429.

Lee J, Kim SJ, Son TG, Chan SL, Mattson MP. Interferon-gamma is up-regulated in the hippocampus in response to intermittent fasting and protects hippocampal neurons against excitotoxicity. J Neurosci Res. 2006 Jun;83(8):1552-7. PubMed PMID: 16521127.

Mager DE, Wan R, Brown M, Cheng A, Wareski P, Abernethy DR, Mattson MP. Caloric restriction and intermittent fasting alter spectral measures of heart rate and blood pressure variability in rats. FASEB J. 2006 Apr;20(6):631-7. PubMed PMID: 16581971.

Barboza PS, Hume ID. Physiology of intermittent feeding: integrating responses of vertebrates to nutritional deficit and excess.Physiol Biochem Zool. 2006 Mar-Apr;79(2):250-64. Epub 2006 Feb 7. PubMed PMID: 16555185.

Tapia PC. Sublethal mitochondrial stress with an attendant stoichiometric augmentation of reactive oxygen species may precipitate many of the beneficial alterations in cellular physiology produced by caloric restriction, intermittent fasting, exercise and dietary phytonutrients: "Mitohormesis" for health and vitality. Med Hypotheses. 2006;66(4):832-43. Epub 2005 Oct 18. PubMed PMID: 16242247.

Michalsen A, Riegert M, Lüdtke R, Bäcker M, Langhorst J, Schwickert M, Dobos GJ. Mediterranean diet or extended fasting's influence on changing the intestinal microflora, immunoglobulin A secretion and clinical outcome in patients with rheumatoid arthritis and fibromyalgia: an observational study. BMC Complement Altern Med. 2005 Dec 22;5:22. PubMed PMID: 16372904; PubMed Central PMCID: PMC1352378.

Halberg N, Henriksen M, Söderhamn N, Stallknecht B, Ploug T, Schjerling P, Dela F. Effect of intermittent fasting and refeeding on insulin action in healthy men. J Appl Physiol (1985). 2005 Dec;99(6):2128-36. Epub 2005 Jul 28. PubMed PMID: 16051710.

Ahmet I, Wan R, Mattson MP, Lakatta EG, Talan M. Cardioprotection by intermittent fasting in rats. Circulation. 2005 Nov 15;112(20):3115-21. Epub 2005 Nov 7. PubMed PMID: 16275865.

Descamps O, Riondel J, Ducros V, Roussel AM. Mitochondrial production of reactive oxygen species and incidence of age-associated lymphoma in OF1 mice: effect of alternate-day fasting. Mech Ageing Dev. 2005 Nov;126(11):1185-91. PubMed PMID: 16126250.

Mattson MP, Wan R. Beneficial effects of intermittent fasting and caloric restriction on the cardiovascular and cerebrovascular systems. J Nutr Biochem. 2005 Mar;16(3):129-37. Review. PubMed PMID: 15741046.

Aksungar FB, Eren A, Ure S, Teskin O, Ates G. Effects of intermittent fasting on serum lipid levels, coagulation status and plasma homocysteine levels. Ann Nutr Metab. 2005 Mar-Apr;49(2):77-82. Epub 2005 Mar 29. PubMed PMID: 15802901.

Wan R, Camandola S, Mattson MP. Intermittent fasting and dietary supplementation with 2-deoxy-D-glucose improve functional and metabolic cardiovascular risk factors in rats. FASEB J. 2003 Jun;17(9):1133-4. Epub 2003 Apr 22. PubMed PMID: 12709404.

Anson RM, Guo Z, de Cabo R, Iyun T, Rios M, Hagepanos A, Ingram DK, Lane MA, Mattson MP. Intermittent fasting dissociates beneficial effects of dietary restriction on glucose metabolism and neuronal resistance to injury from calorie intake. Proc Natl Acad Sci U S A. 2003 May 13;100(10):6216-20. Epub 2003 Apr 30. PubMed PMID: 12724520; PubMed Central PMCID: PMC156352.

Rocha NS, Barbisan LF, de Oliveira ML, de Camargo JL. Effects of fasting and intermittent fasting on rat hepatocarcinogenesis induced by diethylnitrosamine. Teratog Carcinog Mutagen. 2002;22(2):129-38. PubMed PMID: 11835290.

Pedersen CR, Hagemann I, Bock T, Buschard K. Intermittent feeding and fasting reduces diabetes incidence in BB rats.Autoimmunity. 1999;30(4):243-50. PubMed PMID: 10524500.

Krízová E, Simek V. Influence of intermittent fasting and high-fat diet on morphological changes of the digestive system and on changes of lipid metabolism in the laboratory mouse. Physiol Res. 1996;45(2):145-51. PubMed PMID: 9496764.
 
Nir I, Harvey S, Nitsan Z, Pinchasov Y, Chadwick A. Effect of intermittent feeding on blood plasma growth hormone and prolactin in chickens of a heavy breed. Br Poult Sci. 1983 Jan;24(1):63-70. PubMed PMID: 6831277.

Kozubík A, Pospísil M. Protective effect of intermittent fasting on the mortality of gamma-irradiated mice. Strahlentherapie. 1982 Dec;158(12):734-8. PubMed PMID: 6761903.

Vondra K, Rath R, Bass A, Kuzela L, Slabochová Z. [Prolonged intermittent fasting in obese women. Effect on activity of energy metabolism enzymes, glycogen concentration, protein and DNA in skeletal muscle (author's transl)]. Cas Lek Cesk. 1976 Apr;115(15):454-7. Czech. PubMed PMID: 1268896.
: 
Simek V. Energy metabolism of golden hamsters adapted to intermittent fasting: influence of season and sex. Physiol Bohemoslov. 1974;23(5):437-46. PubMed PMID: 4278700.

Kreisler K, Petrásek R. Changes of carbohydrate metabolism during satiety and after varying periods of fasting in rats adapted to intermittent starvation. Physiol Bohemoslov. 1974;23(3):271-6. PubMed PMID: 4280593.

Ruckebusch M, Ferré JP. [Digestive tract alterations connected with intermittent fasting in rats]. Z Zellforsch Mikrosk Anat. 1973 Jun 20;140(1):1552-6. French. PubMed PMID: 4730780.

Stewart WK, Fleming LW, Robertson PC. Massive obesity treated by intermittent fasting. A metabolic and clinical study. Am J Med. 1966 Jun;40(6):967-86. PubMed PMID: 5936189.

Intermittent food restriction. Nutr Rev. 1966 Mar;24(3):83-6. Review. PubMed PMID: 5324330.

Schless GL, Duncan GG. The beneficial effect of intermittent total fasts on the glucose tolerance in obese diabetic patients.Metabolism. 1966 Feb;15(2):98-102. PubMed PMID: 5901780.

Duncan GG, Hunscher MA, Cristofori FC, Duncan TG, Schless GL. Intermittent total fasts and obesity; indications, results and preventable hazards. Postgrad Med. 1965 Nov;38(5):523-35. PubMed PMID: 5833523.

DUNCAN GG. INTERMITTENT FASTS IN THE CORRECTION AND CONTROL OF INTRACTABLE OBESITY. Trans Am Clin Climatol Assoc. 1962;74:121-9. PubMed PMID: 14047310; PubMed Central PMCID: PMC2249073.

INTERMITTENT fasting and longevity in rats. Nutr Rev. 1946 Jul;4(7):218. PubMed PMID: 20992558.

CARLSON AJ, HOELZEL F. Apparent prolongation of the life span of rats by intermittent fasting. J Nutr. 1946 Mar;31:363-75. PubMed PMID: 21021020.