February 2018 Issue

Fasting Regimens for Weight Loss
By Densie Webb, PhD, RD
Today's Dietitian
Vol. 20, No. 2, P. 34

They're all the rage, but do they work?

The practice of fasting dates back millennia, to the time of Hippocrates and Plato. Even long before that, food scarcity was a common occurrence, and it's unlikely our predecessors ate three square meals per day plus snacks, a situation that created involuntary periods of fasting. Today, fasting is generally defined as the abstinence from some or all food or drink, or both, for a specified period of time. However, fasting can take many forms, from the currently popular 5:2 diet (eat normally, but healthfully, for five days of the week and consume only 500 to 600 kcal on two nonconsecutive days) to the fasting pattern of Muslims during Ramadan, in which fasting (no food or drink) occurs from sunrise to sunset for a month. Some type of fasting is a common practice among many faiths, including Judaism, evangelical Christianity, Hinduism, and Catholicism. But today, fasting has become a popular dietary practice, regardless of religious affiliation.

Type "fasting diet books" in your search bar, and no fewer than 40 titles pop up. It's clear that fasting is a sought-after method for weight control and improved health. While diet-induced obesity has been attributed to increased calorie intake and lack of physical activity, a growing body of research suggests that the timing of meals, especially the last meal of the day, may be important for health. Specifically, research suggests that time-restricted feeding and intermittent fasting may not only aid weight management but also reduce the risk of CVD and improve blood glucose control.

While the term "fasting" usually refers to going without food and, in some instances, without drink for an extended period of time, there are many types of fasting. It can refer to alternating zero-calorie days, significantly cutting calories two days per week, fasting three days per month, or extended overnight fasting between the evening meal and breakfast the next morning. Combing through the research on the topic can be confusing because even the literature varies in what's considered "fasting," and the study designs and findings are inconsistent.

The Research
A large body of research exists on laboratory rats and mice to show that intermittent fasting can have profound beneficial effects on everything from diabetes and CVD to Parkinson's disease and stroke.1 Various types of intermittent fasting in animals have resulted in less diabetes, cancers, and neurodegenerative disease, with animals living 30% longer than those allowed to eat every day.2-5 There are far fewer studies in humans. And, according to Michelle Harvie, PhD, research dietitian at the Prevent Breast Cancer research unit in Manchester, England, "Many findings in mice won't translate directly to humans."

While animal studies far outnumber those in humans, there have been some clinical trials designed to test the efficacy of fasting. Two studies in obese women at risk of breast cancer compared a calorie-restricted diet (25% reduction in daily calories) with a 5:2 fasting regimen. While both groups lost similar amounts of weight, those on the fasting regimen lost more abdominal fat and experienced a greater improvement in insulin sensitivity.6,7 Another study of obese women and men found that following an alternate-day fast (consuming 25% of energy needs on the fast day and regular intake on the following day) resulted in significant weight loss, significant decreases in body fat, and a reduction in triglycerides, LDL cholesterol, and systolic blood pressure.8

Researchers conducted a pilot study of obese men and women in which subjects were assigned to either a daily calorie-restricted diet (a calorie deficit of 400 kcal) or alternate day, zero-calorie days for eight weeks. After the study period, there were 24 weeks of unsupervised follow-up to assess weight regain. While both groups lost weight and there was no difference in weight regain at 24 weeks, those on the alternate fasting days lost fat mass and gained lean mass, while those on the calorie-restricted diet gained both fat and lean body mass.9 The disadvantage of this type of regimen is the intense hunger that occurs on fasting days, which may result in a lack of adherence.

The American Heart Association (AHA) published a scientific statement on meal timing and frequency in the February 2017 issue of Circulation.10 After reviewing the research, a consensus was reached that both alternate-day fasting and periodic fasting regimens result in a significant weight loss of 3% to 8% after three to 24 weeks. The review also found that some trials of intermittent fasting reduced total cholesterol (reductions range from 6% to 21%), LDL cholesterol (reductions range from 7% to 32%), and triglycerides (reductions range from 16% to 42%), while others found no effects. The AHA statement concluded that while there's evidence that both alternate-day fasting and periodic fasting may be effective for short-term weight loss, there isn't enough evidence to determine whether it's effective long term. It also was concluded that a weight loss of 6% or more may be required for fasting to be effective for lowering blood pressure. Another recent review of 16 intervention trials to test the efficacy of intermittent fasting regimens found that 11 reported statistically significant weight loss.11

Extended overnight fasting also has been suggested to be beneficial. A study of eight overweight young adults found that increasing the overnight fasting period to ≥14 hours resulted in statistically significant decreases in energy intake and weight, as well as satiety at bedtime and improved sleep.12 If the last meal of the day occurs at 8 PM and breakfast at 7 AM, for example, meals would have to shift to extend the overnight fast by three hours.

But again, there's disagreement. Valter Longo, PhD, director of the Longevity Institute at the University of Southern California, says, "Prolonged overnight fasting for more than 12 hours is actually dangerous." He refers to research showing that skipping breakfast increases mortality and CVD. In addition, he says that fasting for more than 12 to 14 hours results in a 50% increase in the risk of having a cholecystectomy (removal of the gallbladder). Longo has studied the health effects of fasting and has developed the fasting mimicking diet (FMD), which advocates fasting five consecutive days per month in the form of a calorie-restricted diet, and he offers a patented meal program for the fasting days. While his fasting regimen is low in protein, others say higher protein is better. The FMD is also low in sugars but high in unsaturated fats; the specifics are spelled out in Longo's book The Longevity Diet: Discover the New Science Behind Stem Cell Activation and Regeneration to Slow Aging, Fight Disease, and Optimize Weight. Unlike other fasting regimens, the FMD suggests that fasting days need to be consecutive. "You probably would only get partial effects from nonconsecutive days," Longo says. All proceeds from the sale of the book go back to research in the area of the FMD.

Animal studies support the theory that intermittent fasting and restricting the availability of food to certain hours can improve metabolic profiles and reduce the risks of obesity and obesity-related conditions. However, experts concur that more clinical trials in humans are needed to establish the effects of fasting on preventing or delaying disease.

How Fasting Improves Health
According to research, fasting may lead to improved health because it influences circadian rhythms and other systems in the body. The circadian rhythms of the body are controlled by the central clock of the hypothalamus. Other organs in the body are responsive to the food supply, and restriction of food intake can reset these clock rhythms.10 In addition, intermittent fasting regimens may have positive effects on the gut microbiome, which has its own circadian rhythm.11 Weight loss can result not only from calorie restriction but also from a temporary increase in resting energy expenditure (REE). During the first days of starvation, REE increases by about 5%. It's been suggested that this could be due in part to the increased energy cost of recycling fatty acids, glucose storage, and gluconeogenesis.13,14 During a fasting period, fatty acids are released from fat cells and enter the liver, where they're converted to ketone bodies (beta-hydroxybutyrate and acetoacetate), which provide an energy source for muscles and neurons.15,16 These ketone bodies counteract disease processes, such as protecting neurons against degeneration—at least in animals under experimental conditions. There's also evidence that fasting can enhance the ability of cells to remove damaged proteins and organelles.17 However, when ketone levels get too high, as can happen in people with type 1 diabetes, the result is ketoacidosis, which can be life threatening.

To Fast or Not to Fast
For obese individuals with no underlying health conditions, the evidence for fasting as a weight loss tool is stronger than the evidence in humans for protection against disease. Fasting may be a viable weight loss option for obese individuals who can't stick to a daily calorie restriction. Even so, there are downsides to fasting—extreme hunger, headaches, and a possible drop in blood sugar. Before counseling a client or patient on fasting, they should get the green light from their primary health care provider, especially if they have any existing health conditions.

If a client or patient has been given the OK and wants to fast, Mark P. Mattson, PhD, principal investigator in the Laboratory of Neurosciences at the National Institute on Aging recommends the following approaches18:

• two nonconsecutive days each week, eat only one meal, and the other five days eat normally; or
• five days each week, don't eat between the hours of 6 PM and 10 AM.

Mattson believes that short fasts of 16 to 24 hours may activate adaptive stress responses that protect against disease. He also recommends keeping close contact with patients via text or social media to monitor their progress and provide support for this new eating pattern. However, as previously discussed, not everyone agrees with this assessment of extended overnight fasting.

There's clear disagreement even among researchers on the benefits of fasting and which type of fasting would be best for which individuals. "We really don't know the level of restriction and the type of diet that's optimal," Harvie says, adding that researchers also don't know the potential long-term benefits or drawbacks for normal-weight people.

Fasting, as with any other lifestyle change, requires discipline, but reducing intake a few days per month may be more acceptable than chronic calorie reduction. And if more clinical studies bear out the findings in animals, fasting could be another tool in the weight management toolbox.

— Densie Webb, PhD, RD, is a freelance writer, editor, and industry consultant based in Austin, Texas.

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2. Goodrick CL, Ingram DK, Reynolds MA, Freeman JR, Cider NL. Differential effects of intermittent feeding and voluntary exercise on body weight and lifespan in adult rats. J Gerontol. 1983;38(1):36-45.

3. 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;26(5):759-765.

4. Lee C, Raffaghello L, Brandhorst S, et al. Fasting cycles retard growth of tumors and sensitize a range of cancer cell types to chemotherapy. Sci Transl Med. 2012;4(124):124ra27.

5. Arumugam TV, Phillips TM, Cheng A, Morrell CH, Mattson MP, Wan R. Age and energy intake interact to modify cell stress pathways and stroke outcome. Ann Neurol. 2010;67(1):41-52.

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7. Harvie M, Wright C, Pegington M, et al. The effect of intermittent energy and carbohydrate restriction v. daily energy restriction on weight loss and metabolic disease risk markers in overweight women. Br J Nutr. 2013;110(8):1534-1547.

8. Varady KA, Bhutani S, Church EC, Klempel MC. Short-term modified alternate-day fasting: a novel dietary strategy for weight loss and cardioprotection in obese adults. Am J Clin Nutr. 2009;90(5):1138-1143.

9. Catenacci VA, Pan Z, Ostendorf D, et al. A randomized pilot study comparing zero-calorie alternate-day fasting to daily caloric restriction in adults with obesity. Obesity (Silver Spring). 2016;24(9):1874-1883.

10. St-Onge MP, Ard J, Baskin ML, et al. Meal timing and frequency: implications for cardiovascular disease prevention: a scientific statement from the American Heart Association. Circulation. 2017;135(9):e96-e121.

11. Patterson RE, Sears DD. Metabolic effects of intermittent fasting. Ann Rev Nutr. 2017;37:371-393.

12. Gill S, Panda S. A smartphone app reveals erratic diurnal eating patterns in humans that can be modulated for health benefits. Cell Metab. 2015;22(5):789-798.

13. Siervo M, Faber P, Lara J, et al. Imposed rate and extent of weight loss in obese men and adaptive changes in resting and total energy expenditure. Metabolism. 2015;64(8):896-904.

14. Soeters MR, Soeters PB, Schooneman MG, Houten SM, Romijn JA. Adaptive reciprocity of lipid and glucose metabolism in human short-term starvation. Am J Physiol Endocrinol Metab. 2012;303(12):E1397-E1407.

15. McNally MA, Hartman AL. Ketone bodies in epilepsy. J Neurochem. 2012;121(1):28-35.

16. Kashiwaya Y, Bergman C, Lee JH, et al. A ketone ester diet exhibits anxiolytic and cognition-sparing properties, and lessens amyloid and tau pathologies in a mouse model of Alzheimer's disease. Neurobiol Aging. 2013;34(6):1530-1539.

17. Jamart C, Naslain D, Gilson H, Francaux M. Higher activation of autophagy in skeletal muscle of mice during endurance exercise in the fasted state. Am J Physiol Endocrinol Metab. 2013;305(8):E964-E974.

18. Mattson MP. Challenging oneself intermittently to improve health. Dose Response. 2014;1