The Secret Life of Fat - Book Review
- POSTED ON: Oct 05, 2017



The Secret Life of Fat, the Science Behind the Body’s Least Understood Organ and What it Means for Youby Sylvia Tara, PhD (2017)


This book brings cutting-edge research together with historical perspectives to reveal fat's true identity: an endocrine organ that is critical to our health.

The Secret Life of Fat is not a diet book.  It’s a book about how fat works, about understanding body fat - specifically, its role, why it is so difficult to fight, and how it works differently for different people.

Beginning with the question “Why is it easier for some people to stay thin than others?”  Biochemist, Sylvia Tara, investigates the biology of fat and its vital purposes in the body, from reproduction to immunity. Then she examines the genetic, dietary, and other types of influences on body fat. 

She states:


“Fat enhances our brain size, strengthens our bones and immune system, helps wound healing, and can even prolong our lives.”


“Through its most powerful messenger, leptin, fat can influence our appetites. 

It can cause our muscles to reduce their energy usage. 

It can alter our sympathetic nervous system, and control the flow of hormones such as thyroid, adrenaline, and noradrenaline. 

Most profoundly, it can influence our thoughts and elicit stronger responses to food, lower our inhibition to eating, and cause us to misjudge how much we’ve eaten. 

Fat, it turns out, is capable of mind control !”


Once we swallow food we each process it differently.  Science has shown us that food affects our hormones, and hormones affect our fat.  Insulin, leptin, ghrelin, adiponectin, estrogen, testosterone, thyroid, and other hormones influence our weight.”


Biology explains why it’s so hard to keep off the weight once you’ve lost it: People who are at a particular weight because of dieting, metabolize food differently than people who are at that same weight naturally. “Somehow, the remaining body fat of the reduced-obese,” Tara writes, manages “to survive on fewer calories than before, as though it had found another means to thrive.”

After discussing the scientific nature of fat, Tara describes her own weight struggles, and recommends persistence as the main tool for dieters, combined with any diet that is “customized for you biologically, psychologically, and socially”.


Fat Cells are Forever
- POSTED ON: Oct 04, 2017


Once fat cells reach a certain size -- that is, they become filled to capacity with fat content -- then new fat cells will begin to form.  The fat cell number and size increases and shrinks based on deposits from food intake.
“We have a seemingly infinite capacity to recruit new fat cells, but we cannot get rid of them once they have been recruited" said Michael Rosenbaum, associate professor of clinical pediatrics and medicine at Columbia University. "in most cases, weight gain initially reflects ... enlargement of existing fat cells followed by an increased growth of new fat cells.”

Research has shown that obese people who have weight loss surgery have just as many fat cells two years after the surgery as before it, even though they have become much thinner.

Scientist, Dr. Rudy Leibel, says that "the body controls the number of its fat cells as carefully as it controls the amount of its fat". Fat cells die and new ones are born throughout life. Scientists have found that fat cells live for only about seven years and that every time a fat cell dies, another is formed to take its place.

Below see a 2017 New York Times article about this matter.

Are Fat Cells Forever?
              By Alice Callahan  
       February 17, 2017 - New York Times


Once fat cells are formed, can you ever get rid of them?

The number of fat cells in a person’s body seems to be able to change in only one direction: up. Fat cell number increases through childhood and adolescence and generally stabilizes in adulthood.

But this doesn’t mean that fat cells, or adipocytes, are stagnant. The size of individual fat cells is remarkably variable, expanding and contracting with weight gain or weight loss. And as with most cell types in the body, adipocytes die eventually.

when old ones die, they are replaced by new fat cells,” said Dr. Michael Jensen, an endocrinologist and obesity researcher at the Mayo Clinic. Cell death and production appear to be tightly coupled, so although about 10 percent of adipocytes die each year, they’re replaced at the same rate.

Even among bariatric surgery patients, who can lose massive amounts of weight, the number of fat cells tends to remain the same, although the cells shrink in size, studies show.

Liposuction reduces the number of fat cells in a person’s body, but studies show the weight lost is typically regained within a year. It isn’t known whether this regain occurs through the production of new fat cells or expansion of existing ones.

People who are obese tend to have more fat cells than those who are not, and several studies have found an increase in fat cell number with weight regain following weight loss.

"The fact that fat cell number can be increased but not decreased most likely contributes to the body’s drive to regain weight after weight loss", said Dr. Kirsty L. Spalding, a cell biologist at the Karolinska Institute in Sweden and the lead author of a 2008 study showing that fat cells die and are replaced. Beyond their role in storing fat, adipocytes secrete proteins and hormones that affect energy metabolism.

“Following weight loss, adipocytes become smaller, generally smaller than those from people with a similar B.M.I.,” Dr. Spalding said. One hypothesis is that those smaller cells might send signals to increase appetite and fat storage, which could help to explain why weight loss is so difficult to maintain, though much more research is needed.





Our Weight is Regulated by Our Biological System
- POSTED ON: Jul 13, 2017

I continually read a great many books, articles, blogs, and forum posts on the subject of obesity.

No one,…. not even the most qualified medical doctor or scientist, … knows everything or holds only beliefs that are absolutely correct.

However, I am often amazed by the vast amount of existing misconceptions, myths, and wishful-thinking that gets spread and promoted by people who present themselves as obesity “experts” or “gurus”.

One thing that Scientists know for sure about obesity management, is the sad fact, that no diet, exercise, medication, not even bariatric surgery, will permanently reset the body’s tendency to defend and regain its body weight to its set point .... this generally being the highest weight that has been achieved and maintained for a notable length of time.



Thus, any effective long-term treatment MUST OFFSET the complex neurobiology which is designed to eventually doom every weight-loss attempt to ultimately "fail".

A comprehensive review recently published in Endocrine Reviews describes the complexity of  the biological system that regulates our body weight.

The 30+ page research paper, backed by about 350 scientific citations, was written by the undisputed leaders in the medical field of Endocrinology (Michael Schwartz, Randy Seeley, Eric Ravussin, Rudolph Leibel and colleagues)  and is actually a “Scientific Statement” from the Endocrine Society. 

In other words, these Scientists know that they are talking about when they speak about the Science of Energy Balance, and in this paper they outline in excruciating scientific detail just how complex the biological system that regulates, defends, and restores body weight actually is.

From the Abstract of this research paper:

We included evidence from basic science, clinical, and epidemiological literature to assess current knowledge regarding mechanisms underlying excess body-fat accumulation, the biological defense of excess fat mass, and the tendency for lost weight to be regained.

A major area of emphasis is the science of energy homeostasis, the biological process that maintains weight stability by actively matching energy intake to energy expenditure over time.

Growing evidence suggests that
obesity is a disorder of the energy homeostasis system, rather than simply arising from the passive accumulation of excess weight.

Their position is that, despite all we have learned about this system, we are still far from fully understanding it.

Science knows about one of the pathways, but there are many pathways in a complex network of multiple interacting pathways that involve virtually every part of the brain.

They say that the medical field currently needs a great deal more information about the specifics of this issue:

The identification of neuromolecular mechanisms that integrate short-term and long-term control of feeding behavior, such that calorie intake precisely matches energy expenditure over long time intervals, will almost certainly enable better preventive and therapeutic approaches to obesity.”

To be viable, theories of obesity pathogenesis must account not only for how excess body fat is acquired, but also for how excess body fat comes to be biologically defended.

Answering this question requires an improved understanding of the neuro-molecular elements that underlie a “defended” level of body fat. What are the molecular/neuroanatomic predicates that help establish and defend a “set point” for adiposity? How do these elements regulate feeding behavior and/or energy expenditure, so as to achieve long-term energy balance?
By what mechanisms is an apparently higher set point established and defended in individuals who are obese?”

They conclude that:

Given that recovery of lost weight ... (the normal, physiological response to weight loss irrespective of one’s starting weight) ... is the largest single obstacle to effective long-term weight loss, we cannot overstate the importance of a coherent understanding of obesity-associated alterations of the energy homeostasis system.”


So, in essence, this scientific paper shows why no simple solution to obesity is in sight; details the existence of an enormous Problem; and raises Questions for which Science still needs to find answers.

To get a simple explanation of the basic concept, see: Set Point. 

Any “health & wellness” professional, medical doctor, or guru who claims that any particular Diet, Behavior, or LifeStyle can fundamentally change the part of the body’s biology which acts to protect and restore body fat in the long term is Simply Wrong. 

They are either spreading a Lie, sharing a Myth, or offering a hypothesis for which no proof or reasonable evidence exists… which means that they are simply sharing their own Wishful-Thinking.

At this point, all credible Scientific Research indicates the following:

No matter how much weight gets lost, or is maintained for the short-term, …
No matter whether that weight loss was slow or fast, ...
No matter when food intake occurs ...

No matter whether “unprocessed” or “healthy” food is eaten, ...

Ultimately NO diet or behavior
manages to “reset” the body-weight set point to a lower level,
in order to biologically “stabilize” weight loss for the long-term.






Calorie Restriction = Calorie Restriction.
- POSTED ON: Jul 12, 2017

At the end of the day:
Calorie Restriction
equals
Calorie Restriction.


See the article below from Dr. Arya Sharma, who is one of the world’s top medical obesity specialists.

Dr. Sharma is highly respected by obesity researchers, health professionals. His opinions are based on many years of extensive obesity research as well as many years of practical experience with obese patients. 


Alternate Day Fasting Is No Better Than Any Other Fad Diet
                   by Dr. Arya Sharma,  July 11, 2017

It seems that every year someone else comes up with a diet that can supposedly conquer obesity and all other health problems of civilization.

In almost every case, the diet is based on some “new” insight into how our bodies function, or how our ancestors (read – hunters gatherers (never mind that they only lived to be 35) ate, or how modern foods are killing us (never mind that the average person has never lived longer than ever before), or how (insert remote population here) lives today with no chronic disease.

Throw in some scientific terms like “ketogenic”, “guten”, “anti-oxidant”, “fructose”, or “insulin”, add some level of restriction and unusual foods, and (most importantly) get celebrity endorsement and “testimonials” and you have a best-seller (and a successful speaking career) ready to go.

The problem is that, no matter what the “scientific” (sounding) theories suggest, there is little evidence that the enthusiastic promises of any of these hold up under the cold light of scientific study.


Therefore, I am not the least surprised that the same holds true for the much hyped “alternative-day fasting diet”, which supposedly is best for us, because it mimics how our pre-historic ancestors apparently made it to the ripe age of 35 without obesity and heart attacks.

Thus, a year-long randomized controlled study by John Trepanowski and colleagues, published in JAMA Internal Medicine, shows that alternate day fasting is evidently no better in producing superior adherence, weight loss, weight maintenance, or cardioprotection compared to good old daily calorie restriction (which also produces modest long-term results at best).

In fact, the alternate day fasting group had significantly more dropouts than both the daily calorie restriction and control group (38% vs. 29% and 26% respectively). Mean weight loss was virtually identical between both intervention groups (~6 Kg).

Purists of course will instantly criticize that the study did not actually test alternative-day fasting, as more people dropped out and most of the participants who stayed in that group actually ate more than prescribed on fast days, and less than prescribed on feast days – but that is exactly the point of this kind of study – to test whether the proposed diet works in “real life”, because no one in “real life” can ever be expected to be perfectly compliant with any diet. In fact, again, as this study shows, the more “restrictive” the diet (and, yes, starving yourself every other day is “restrictive”), the greater the dropout rate.

Unfortunately, what counts in real life is not what people SHOULD be doing, but what people actually do.

The question really is
not whether or not alternate-day fasting is better for someone trying to lose weight but rather, whether or not “recommending” someone follows an alternate-day fasting plan (and them trying to follow it the best they can) is better for them. The clear answer from this study is “no”.

So why are all diets the same (in that virtually all of them provide a rather modest degree of long-term weight loss)?

My guess is that no diet (or behavior for that matter) has the capability of fundamentally changing the body’s biology that acts to protect and restore body fat in the long-term. Irrespective of whether a diet leads to weight loss in the short term and irrespective of how it does so (or how slow or fast), ultimately no diet manages to “reset” the body-weight set point to a lower level, that would biologically “stabilize” weight loss in the long-term.

Thus, the amount of long-term weight loss that can be achieved by dieting is always in the same (rather modest) ballpark and it is often only a matter of time before the biology wins out and put all the weight back on.

Clearly, I am not holding my breath for the next diet that comes along that promises to be better than everything we’ve had before.

My advice to patients is, do what works for you, but do not expect miracles – just find the diet you can happily live on and stick to it.


Dr. Arya M. Sharma, MD, PhD, FRCPC is a medical doctor and university professor of medicine and obesity research.  His research focuses on the evidence-based prevention and management of obesity and its complications.

He has authored and co-authored more than 350 scientific articles and has lectured widely throughout the world on the etiology and management of obesity and related cardiovascular disorders. Dr. Sharma is regularly featured as a medical expert in national and international TV and print media and maintains a widely read obesity blog at www.drsharma.ca.

 

I have been observing and experimenting with various forms of Intermittent Fasting since early 2006, which was BEFORE the best-selling intermittent fasting books… including… JUDDD, ADF, EatStopEat, 5/2, and EOD ... were published.  And BEFORE the concept of Intermittent Fasting as a diet became famous on the internet.

This past 12 years, I’ve closely watched many diet “experts” talk about the latest fasting research, while providing their own anecdotal evidence.   I’ve seen both of these offered as evidence to prove the "expert's"  own opinions about the subject. 

As an attorney, I’ve been trained to notice when people improperly characterize evidence, especially when they misstate evidence or misquote a witness in order to prove a point they are trying to make.

This is something that is commonly done by diet “experts”.  Unfortunately even medical doctors whose overall medical expertise and opinions I tend to respect, sometimes engage in this type of Behavior, and apply valid scientific research incorrectly in order to support “a hypothesis with zero proof, which is really no more than that expert’s own wishful thinking.”

For example, even Dr. Jason Fung, who appears to be a very dedicated, well-educated, and experienced medical expert specializing in the area of Diabetes, …(and who is extensively quoted here in the Fasting Blog Category section of DietHobby as an intermittent fasting expert) … sometimes improperly characterizes research evidence in order to prove points which appear to be merely based on his “wishful thinking” due to the lack of valid supporting evidence.

One of Dr. Fung’s hypothesis is that people cannot lose weight by using “calorie restriction”, but that they can lose weight by using “Intermittent fasting”, and he claims that there is a very big difference between these two behaviors.  As evidence for this principle, he often compares scientific Research about Biggest Loser Contestants, who he labels as “Calorie Restricting”, versus scientific Research about Gastric Bypass Participants, who he labels as “Fasting”.

Of course, the main problem with the Comparison is that BOTH of these weight-loss methods are based on Calorie Restriction in that Post-gastric bypass, participants do not “Fast”.  They do not go without eating. After weight-loss surgery they eat small amounts of food daily.  First, they ingest liquid food, then soft food, and then go on to firm food. 

During the first year after my own open RNY gastric bypass, 25 years ago, my experience was similar to what everyone else commonly reports.  I ate between 300 and 600 calories per day … which was as much food as my body would tolerate at the time.  I did not fast.  I did not consciously “restrict calories”,  but instead focused on eating only the amounts and kinds of food that would prevent me from lying on my bed with dry heaves.  I did not fast. My surgery restricted calories for me.

Since both of these forms of eating behavior leading to weight-loss were based on Calorie Restriction, Dr. Fung misstated the evidence which he provided as proof for his hypothesis.  As a result, his hypothesis lacks proof.  This reduces it back to his own personal “wishful thinking”.   Over the past several years, Dr. Fung has failed to address or provide any explanation for this error, even though I have seen it pointed out to him on several different occasions.

I find it interesting that Dr. Fung also relies heavily on Dr Krista Varady’s past scientific research on Intermittent Fasting to prove that Intermittent Fasting is superior to Calorie Restriction… although in her own words .... Dr. Varady says that Intermittent Fasting is a form of "Calorie-Restriction".

 When Dr. Varady was interviewed about this recent research study which is the subject of Dr. Sharma’s article, she said:


I really thought people would have an easier time and lose more weight on the [intermittent fasting diet] and I was shocked they lost the same amount,” says study author Dr. Krista Varady, an associate professor of nutrition the University of Illinois at Chicago and author of the book The Every-Other-Day Diet.The take-home message for me is that this diet isn’t for everyone.”

"I don't think there's anything magical to the diet at all," she said of alternate-day fasting.
"I think it's just another way of tricking people into eating less food or helping people to kind of monitor how much food intake there is or how much food they're taking in."

You can find the complete study in my previous article: “Fasting is No Better For You Than Regular Calorie Restriction - new Scientific Study”.

 


Fasting is No Better For You Than Regular Calorie Restriction - new Scientific Study
- POSTED ON: May 03, 2017

A Scientific Study was recently published concluding that an alternate-day fasting diet was NOT superior to a daily calorie restriction diet for Metabolically Healthy Obese Adults with regard to adherence, weight loss, weight maintenance, or improvement in risk indicators for cardiovascular disease (including insulin resistance).

The lead researcher in this study, Dr. Krista Varady, has previously done extensive research on Alternate Day Fasting.  Those studies are currently considered the best scientific authority on Intermittent Fasting, and her previous research findings have often been extensively quoted by the majority of Intermittent Fasting Gurus, including Dr. Jason Fung, author of The Obesity Code (2016) and The Complete Guide to Fasting (2016)

Below is a recent article from TIME

 


Fasting Isn’t Better for You Than Regular Dieting
Alexandra Sifferlin   May 01, 2017    TIME

Losing weight is hard, which is why weight loss experts have long searched for different approaches to make it easier for people. One strategy gaining steam is intermittent fasting, where people fast or lower their calories substantially for a short period of time. (This diet plan also has potential lifespan-extending benefits.)

But new research published in JAMA Internal Medicine suggests that the fasting diet may not be the weight loss key it's been hyped up to be.

In the new trial, researchers wanted to know whether people who tried a fasting diet would be more successful than those on a standard diet. They told 100 people with obesity to follow one of three diets for a year. Some were told to cut their calorie consumption by 25% per day—a typical calorie restriction diet—while others did an alternate-day fasting diet, where they ate about 500 calories on “fast” days and whatever they wanted on “feast" days. The last group, which served as the control group, ate what they normally would.

The researchers expected that the people in the fasting group would lose more weight and have an easier time sticking to the diet than regular dieters, but the results didn't reflect that. At the end of the year, people who did the fasting diet and those who just cut calories both lost an average of 13 pounds. However, people in the fasting group actually had a harder time sticking to the diet, and more people in that group dropped out of the study.

I really thought people would have an easier time and lose more weight on the [intermittent fasting diet] and I was shocked they lost the same amount,” says study author Dr. Krista Varady, an associate professor of nutrition the University of Illinois at Chicago and author of the book The Every-Other-Day Diet. “The take-home message for me is that this diet isn’t for everyone.”

The researchers also did not find significant differences in other health measures between the dieting groups, like blood pressure, heart rate or insulin resistance.

Dr. Varady says that while half of the people in the fasting group "could barely do the diet," there were several people who were very successful, losing between 20 to 50 pounds. Those findings suggest that some people do respond well to the diet.

Still, what works for one person clearly doesn’t work for everyone. “If people have failed other diets, maybe this will work,” Dr. Varady says. “People will pick what diet works best for them."


Below are Excepts from a recent CNN article about this scientific research study. 
 

The study suggests that there is no significant difference between fasting and the other popular weight loss strategy of simply restricting how many daily calories you consume.

Dr. Varady said that, before the study, she thought alternate-day fasting would be an easier diet to adhere to because it allowed for a "break" from dieting every day.

"We were a little bit shocked to see that it was actually the calorie-restriction group that seemed like they could stick better to their daily calorie goals. Whereas the alternate-day fasting group, they were kind of wavering," said Dr. Varady, who authored a book about alternate-day fasting called "The Every-Other-Day Diet."

"Instead of eating the 500 calories on the fasting days, they were eating a couple hundred calories more on those days," she said.

'Not one diet fits everyone'

All in all, the new study showed that alternate-day fasting may be difficult to follow but can be effective in reducing obesity, said Valter Longo, a professor at the University of Southern California and director of the university's Longevity Institute. He was not involved in the study.

However, "because it requires a major effort every other day, it is unlikely to be applicable to the great majority of the obese population, particularly in the absence of the close monitoring carried out in the clinical study," Longo said.

For overweight or obese adults who might be interested in alternate-day fasting as a weight loss approach, Dr. Varady advised taking the time to really determine whether it is the best option.  "I really think people just need to find what works for them," she said. "Not one diet fits everyone."

"I don't think there's anything magical to the diet at all," she said of alternate-day fasting. "
I think it's just another way of tricking people into eating less food or helping people to kind of monitor how much food intake there is or how much food they're taking in."

Below is a copy of the published research study.

This study can also be found at:
http://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2623528

May 1, 2017 

Effect of Alternate-Day Fasting on Weight Loss, Weight Maintenance, and Cardioprotection Among Metabolically Healthy Obese Adults
A Randomized Clinical Trial

John F. Trepanowski, PhD1; Cynthia M. Kroeger, PhD1,2; Adrienne Barnosky, MD1; et al Monica C. Klempel, PhD1; Surabhi Bhutani, PhD1; Kristin K. Hoddy, PhD, RD1; Kelsey Gabel, MS, RD1; Sally Freels, PhD3; Joseph Rigdon, PhD4; Jennifer Rood, PhD5; Eric Ravussin, PhD5; Krista A. Varady, PhD1

Author Affiliations Article Information
JAMA Intern Med. Published online May 1, 2017. doi:10.1001/jamainternmed.2017.0936


Key Points

Question  Is alternate-day fasting more effective for weight loss and weight maintenance compared with daily calorie restriction?

Findings  This randomized clinical trial included 100 metabolically healthy obese adults. Weight loss after 1 year in the alternate-day fasting group (6.0%) was not significantly different from that of the daily calorie restriction group (5.3%), relative to the no-intervention control group.

Meaning  Alternate-day fasting does not produce superior weight loss or weight maintenance compared with daily calorie restriction.

Abstract

Importance  Alternate-day fasting has become increasingly popular, yet, to date, no long-term randomized clinical trials have evaluated its efficacy.

Objective  To compare the effects of alternate-day fasting vs daily calorie restriction on weight loss, weight maintenance, and risk indicators for cardiovascular disease.

Design, Setting, and Participants  A single-center randomized clinical trial of obese adults (18 to 64 years of age; mean body mass index, 34) was conducted between October 1, 2011, and January 15, 2015, at an academic institution in Chicago, Illinois.

Interventions  Participants were randomized to 1 of 3 groups for 1 year: alternate-day fasting (25% of energy needs on fast days; 125% of energy needs on alternating “feast days”), calorie restriction (75% of energy needs every day), or a no-intervention control. The trial involved a 6-month weight-loss phase followed by a 6-month weight-maintenance phase.

Main Outcomes and Measures  The primary outcome was change in body weight. Secondary outcomes were adherence to the dietary intervention and risk indicators for cardiovascular disease.

Results  Among the 100 participants (86 women and 14 men; mean [SD] age, 44 [11] years), the dropout rate was highest in the alternate-day fasting group (13 of 34 [38%]), vs the daily calorie restriction group (10 of 35 [29%]) and control group (8 of 31 [26%]). Mean weight loss was similar for participants in the alternate-day fasting group and those in the daily calorie restriction group at month 6 (–6.8% [95% CI, –9.1% to –4.5%] vs –6.8% [95% CI, –9.1% to –4.6%]) and month 12 (–6.0% [95% CI, –8.5% to –3.6%] vs –5.3% [95% CI, –7.6% to –3.0%]) relative to those in the control group. Participants in the alternate-day fasting group ate more than prescribed on fast days, and less than prescribed on feast days, while those in the daily calorie restriction group generally met their prescribed energy goals. There were no significant differences between the intervention groups in blood pressure, heart rate, triglycerides, fasting glucose, fasting insulin, insulin resistance, C-reactive protein, or homocysteine concentrations at month 6 or 12. Mean high-density lipoprotein cholesterol levels at month 6 significantly increased among the participants in the alternate-day fasting group (6.2 mg/dL [95% CI, 0.1-12.4 mg/dL]), but not at month 12 (1.0 mg/dL [95% CI, –5.9 to 7.8 mg/dL]), relative to those in the daily calorie restriction group. Mean low-density lipoprotein cholesterol levels were significantly elevated by month 12 among the participants in the alternate-day fasting group (11.5 mg/dL [95% CI, 1.9-21.1 mg/dL]) compared with those in the daily calorie restriction group.

Conclusions and Relevance  Alternate-day fasting did not produce superior adherence, weight loss, weight maintenance, or cardioprotection vs daily calorie restriction.

Trial Registration  clinicaltrials.gov Identifier: NCT00960505

Introduction

The first-line therapy prescribed to obese patients for weight loss is daily calorie restriction.1 However, many patients find it difficult to adhere to a conventional weight-loss diet because food intake must be limited every day.2 As such, adherence to daily calorie restriction decreases after 1 month and continues to decline thereafter.3- 5 In light of this limitation, another approach that requires individuals to restrict calories only every other day was developed.6 This strategy is called alternate-day fasting and involves a fast day where individuals consume 25% of their usual intake (approximately 500 kcal), alternated with a “feast day” where individuals are permitted to consume food ad libitum. Findings from short-term studies indicate that participants lose 3% to 7% of body weight after 2 to 3 months of alternate-day fasting and experience improvements in lipid profiles, blood pressure, and insulin sensitivity.7- 13

Alternate-day fasting regimens have increased in popularity during the past decade, and several best-selling diet books14,15 have promoted this approach. More than 1 million copies of these books have been sold in the United States and United Kingdom to date. Despite the growing popularity of alternate-day fasting, to our knowledge, no long-term randomized clinical trials have evaluated its efficacy or compared this regimen with a conventional weight-loss diet.

We conducted a 1-year, randomized clinical trial to compare the effects of alternate-day fasting vs daily calorie restriction on body weight and risk indicators for cardiovascular disease. We hypothesized that the participants in the alternate-day fasting group would be more adherent to their diet, achieve greater weight loss, and experience more pronounced improvements in risk indicators for cardiovascular disease during the 6-month weight-loss phase compared with those in the daily calorie restriction group. We also hypothesized that the alternate-day fasting group would better maintain their weight loss and sustain their improvements in risk indicators for cardiovascular disease during the 6-month weight-maintenance phase compared with the daily calorie restriction group.

Methods

Participants

We conducted the trial between October 1, 2011, and January 15, 2015, at the University of Illinois at Chicago. Participants were recruited from the Chicago area by means of flyers placed around the university and were screened via a questionnaire, an assessment of body mass index, and a pregnancy test. Individuals included were men and women between 18 and 65 years of age, with a body mass index between 25.0 and 39.9 (calculated as weight in kilograms divided by height in meters squared) who had previously been sedentary (<60 minutes per week of light activity for the 3 months prior to the study).

Exclusion criteria were a history of cardiovascular disease or type 1 or 2 diabetes, use of medications that could affect study outcomes, unstable weight for 3 months prior to the beginning of the study (>4-kg weight loss or gain), perimenopause or otherwise irregular menstrual cycle, pregnancy, and currently smoking. The protocol was approved by the Office for the Protection of Research Subjects at the University of Illinois at Chicago, and written informed consent was obtained from all participants. The full protocol is available in Supplement 1.

Randomization and Intervention Groups

Participants were randomized in a 1:1:1 ratio to an alternate-day fasting group, daily calorie restriction group, or no-intervention control group. Randomization was performed by a stratified random sampling procedure by sex, age (18-42 years and 43-65 years), and body mass index (25.0-32.5 and 32.6-39.9). Block size ranged from 1 to 11 participants. The active trial duration was 1 year and consisted of a baseline phase (1 month), a weight-loss phase (6 months), and a weight-maintenance phase (6 months) (eFigure 1 in Supplement 2). We chose this design because weight loss typically peaks at 6 months during a lifestyle intervention.16 During the baseline phase, all participants ate their usual diet and maintained a stable weight. Baseline total energy expenditure was measured using doubly labeled water.17 All participants were instructed not to change their physical activity habits throughout the trial (eg, not to join a gym) to avoid potential confounding.

Weight-Loss Phase

Participants in the alternate-day fasting group and those in the daily calorie restriction group were provided with all meals during the first 3 months of the trial and received dietary counseling thereafter (eFigure 1 in Supplement 2). During the 6-month weight-loss phase, the intervention groups were instructed to reduce their energy intake by a mean of 25% per day. To achieve this reduction, the alternate-day fasting group was instructed to consume 25% of baseline energy intake as a lunch (between 12 pm and 2 pm) on fast days and 125% of baseline energy intake split between 3 meals on alternating feast days. The daily calorie restriction group was instructed to consume 75% of baseline energy intake split between 3 meals every day. The provided meals were in accordance with the American Heart Association guidelines18 for macronutrient intake, with 30% of energy as fat, 55% as carbohydrate, and 15% as protein. From months 4 to 6, when food was no longer provided, intervention participants met individually with a dietician or nutritionist weekly to learn how to continue with their diets on their own.

Weight-Maintenance Phase

At the beginning of the 6-month weight-maintenance phase, total daily energy expenditure was reassessed using doubly labeled water.17 Participants were instructed to maintain their body weight during this phase. Participants in the alternate-day fasting group were instructed to consume 50% of energy needs as a lunch on fast days and 150% of energy needs split between 3 meals on alternating feast days. Participants in the daily calorie restriction group were instructed to consume 100% of energy needs split between 3 meals every day. Intervention participants met with the dietician individually each month to learn cognitive behavioral strategies to prevent weight regain19 and received personalized energy targets for weight maintenance based on results from doubly labeled water.

Control Group Protocol

Participants in the control group were instructed to maintain their weight throughout the trial and not to change their eating or physical activity habits. Controls received no food or dietary counseling but visited the research center at the same frequency as the intervention participants (to provide outcome measurements). Controls who completed the 12-month trial received 3 months of free weight-loss counseling and a 12-month gym membership at the end of the study.

Outcome Measures

The primary outcome of the study was change in body weight, which was measured monthly via a digital scale while the participant was in a hospital gown. Fat mass and lean mass were measured every 6 months in the fasted state by dual-energy x-ray absorptiometry (QDR 4500W; Hologic). Visceral fat mass was measured every 6 months by magnetic resonance imaging performed with a 1.5-T magnet (Siemens Vision), and images were analyzed using validated software.20

Mean percentage energy restriction during the weight-loss phase was retrospectively calculated by the intake balance method using doubly labeled water and changes in body composition.21 Physical activity was measured for 7 consecutive days every 6 months using an activity monitor (SenseWear Armband Mini; BodyMedia Inc).22 Dietary intake and adherence to diets was assessed every 3 months with a 7-day food record and analyzed using Nutritionist Pro software (Axxya Systems LLC). Intervention participants were considered to be adherent when their actual energy intake, determined via food records, was within 200 kcal of their prescribed daily energy goal.

Blood samples were obtained following a 12-hour fast every 6 months (collected on the morning after a feast day for the alternate-day fasting group). Secondary outcomes included blood pressure, heart rate, and total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, fasting glucose, fasting insulin, C-reactive protein, and homocysteine concentrations (analytical methods are detailed in the full protocol in Supplement 1). The homeostasis model assessment of insulin resistance was calculated as insulin × glucose/405, where the unit of measure for insulin is in micro-international units per milliliter and the unit of measure for glucose is milligrams per deciliter.23

Statistical Analysis

For the sample size calculation, we estimated that alternate-day fasting would reduce body weight by 15% by month 69,11 and that daily calorie restriction would reduce body weight by 10% by month 6.24 We calculated that 26 participants per group would provide 80% power to detect a significant difference of 5% in body weight between the alternate-day fasting group and the daily calorie restriction group at month 6, using a 2-tailed independent-samples t test with α = .05. We anticipated a dropout rate of 12%. Thus, we initially aimed to recruit 90 participants (30 per group), assuming that 78 participants (26 per group) would complete the trial. We later decided to recruit 100 participants to increase our statistical power because our dropout rate was higher than expected.

Data are shown as mean values (with 95% CIs) unless otherwise noted. A 2-tailed P < .05 was considered statistically significant. Tests for normality were included in the model, and all data were found to be normally distributed. We conducted an intention-to-treat analysis, which included data from all 100 participants who underwent randomization. Results are reported by intention-to-treat analysis unless indicated otherwise. A linear mixed model was used to assess time, diet, and time × diet effects for each outcome. This model provides unbiased estimates of time and treatment effects under a missing-at-random assumption. Time was not assumed to be linear in the model. This strategy allowed for estimation of time and diet effects (and their interaction) without imposing a linear time trend. The analyses were performed using SAS, version 9.4 (SAS Institute, Inc), and R software, version 3.2.2 (R Foundation for Statistical Computing).

Results

Participant Characteristics and Attrition

Of the 222 participants who were screened, 100 (45.0%) were randomly assigned to the diet or control groups, and 69 (69.0% of those assigned) completed the study (Figure 1). The dropout rate was highest in the alternate-day fasting group (13 of 34 [38%]), relative to the daily calorie restriction group (10 of 35 [29%]) and control group (8 of 31 [26%]). More participants in the alternate-day fasting group than in the daily calorie restriction group withdrew owing to difficulties adhering with the diet. All baseline characteristics had comparable distributions between the alternate-day fasting group, the daily calorie restriction group, and the control group (Table 1). The participants were primarily metabolically healthy obese women.

Prescribed vs Actual Energy Intake Determined via Food Records

On the fast day (Figure 2A), participants in the alternate-day fasting group exceeded their prescribed energy goal at months 3 and 6. On the feast day (Figure 2B), participants in the alternate-day fasting group ate less than their prescribed goal at months 3, 6, 9, and 12. Participants in the daily calorie restriction group (Figure 2C) met their prescribed energy goals at months 3, 6, and 12 but ate less than their prescribed goal at month 9. A higher proportion of participants in the daily calorie restriction group were adherent to their energy goals at months 3, 6, 9, and 12 relative to those in the alternate-day fasting group.

Percentage Energy Restriction Determined via Doubly Labeled Water

From baseline to month 6, the alternate-day fasting group achieved a mean (SD) percentage energy restriction of 21% (16%), and the daily calorie restriction group achieved a mean (SD) percentage energy restriction of 24% (16%), with no significant difference between the intervention groups or compared with the control group (eFigure 2 in Supplement 2).

Physical Activity and Dietary Intake

Data on dietary intake are displayed in eTable 1 in Supplement 2. Percentage of energy intake from fat, carbohydrates, and protein did not differ significantly over time in any of the groups. Physical activity, measured as steps per day, did not change during the course of the trial in any group (eTable 2 in Supplement 2). This level of activity is approximately 1000 to 2000 steps per day higher than that of the average overweight or obese adult.25

Weight Loss and Weight Maintenance

Changes in body weight are displayed in Figure 3 and Table 2. Weight loss was not significantly different between the alternate-day fasting group and the daily calorie restriction group at month 6. At the end of the study, total weight loss was –6.0% (95% CI, –8.5% to –3.6%) for the alternate-day fasting group and –5.3% (95% CI, –7.6% to –3.0%) for the daily calorie restriction group, relative to controls, with no significant difference between the intervention groups. Weight regain from months 6 to 12 (–0.8%; 95% CI, –3.2% to 1.7%) was not significantly different between the alternate-day fasting group and the daily calorie restriction group. Moreover, weight regain from months 6 to 12 was not significantly different between the alternate-day fasting group and controls (0.8%; 95% CI, –1.8% to 3.3%), or the daily calorie restriction group and controls (1.5%; 95% CI, –0.8% to 3.9%). Changes in body composition are reported in Table 2. There were no statistically significant differences between the alternate-day fasting group and the daily calorie restriction group for fat mass, lean mass, or visceral fat mass at month 6 or month 12.

Blood Pressure and Heart Rate

Blood pressure was not significantly different between the intervention groups, or relative to controls, at month 6 or month 12 (Table 2). There were also no statistically significant differences in heart rate between the alternate-day fasting group and the daily calorie restriction group at month 6 or month 12 (Table 2).

Plasma Lipids

Changes in plasma lipids during the course of the trial are shown in Table 2. Total cholesterol levels were not significantly different between the intervention groups, or relative to controls, at month 6 or month 12. At month 6, high-density lipoprotein cholesterol levels were significantly elevated in the alternate-day fasting group by 6.2 mg/dL (95% CI, 0.1-12.4 mg/dL) (to convert to millimoles per liter, multiply by 0.0259) vs the daily calorie restriction group, but this effect was no longer observed by month 12. Low-density lipoprotein cholesterol concentrations did not differ significantly between the intervention groups at month 6. At month 12, low-density lipoprotein cholesterol levels significantly increased in the alternate-day fasting group (11.5 mg/dL [95% CI, 1.9-21.1 mg/dL]) (to convert to millimoles per liter, multiply by 0.0259) relative to the daily calorie restriction group. Triglyceride levels did not differ significantly between the intervention groups at month 6 or month 12.


Glucoregulatory and Inflammatory Factors

Changes in glucoregulatory and inflammatory factors are displayed in Table 2. Fasting plasma glucose did not differ significantly between the intervention groups, or relative to controls, at month 6 or month 12. There were also no significant differences in fasting insulin or the homeostasis model assessment of insulin resistance between the intervention groups at month 6 or month 12. High-sensitivity C-reactive protein and homocysteine levels did not differ significantly between the intervention groups, or relative to controls, at month 6 or month 12. We also performed a sensitivity analysis, in which sex and race/ethnicity were included as adjustment covariates in the intention-to-treat mixed model. The inclusion of sex and race/ethnicity did not affect any of the estimated treatment effects reported in Table 2.

Discussion

The results of this randomized clinical trial demonstrated that alternate-day fasting did not produce superior adherence, weight loss, weight maintenance, or improvement in risk indicators for cardiovascular disease compared with daily calorie restriction.

Alternate-day fasting has been promoted as a potentially superior alternative to daily calorie restriction under the assumption that it is easier to restrict calories every other day. However, our data from food records, doubly labeled water, and regular weigh-ins indicate that this assumption is not the case. Rather, it appears as though many participants in the alternate-day fasting group converted their diet into de facto calorie restriction as the trial progressed. Moreover, the dropout rate in the alternate-day fasting group (38%) was higher than that in the daily calorie restriction group (29%) and the control group (26%). It was also shown that more participants in the alternate-day fasting group withdrew owing to dissatisfaction with diet compared with those in the daily calorie restriction group (Figure 1).

Taken together, these findings suggest that alternate-day fasting may be less sustainable in the long term, compared with daily calorie restriction, for most obese individuals. Nevertheless, it is still possible that a certain smaller segment of obese individuals may prefer this pattern of energy restriction instead of daily restriction. It will be of interest to examine what behavioral traits (eg, ability to go for long periods without eating) make alternate-day fasting more tolerable for some individuals than others.

To our knowledge, the present study is the longest and largest trial of alternate-day fasting to date. Previous trials of alternate-day fasting reported weight loss of 3% to 7% after 2 to 3 months of diet.7- 13 Adherence was measured in several previous trials and was shown to be high (eg, participants met their calorie goals on approximately 80%-90% of fast days).7,8,10,11 Most of these past studies provided food on the fast day,7,8,10,11 so the provision of food is not a confounder when comparing past findings with present findings. Food was provided to the intervention participants during the first 3 months of the weight-loss phase to promote adherence26 and show participants the types and quantities of foods that they should be eating. Data from the food records indicated that participants frequently ate extra “nonstudy” foods that were purchased from stores or restaurants.

This finding suggests that limiting caloric intake to approximately 500 kcal every other day may have been difficult for many participants early in the intervention. Future work in this area should examine whether this lack of adherence to alternate-day fasting is due to cognitive, environmental, and/or physiological factors. For instance, measuring changes in subjective appetite (hunger and fullness) in conjunction with modulations in appetite hormones (ghrelin, peptide YY, and glucagon-like peptide-1) could offer some insight into why daily calorie restriction may allow for easier adherence compared with alternate-day fasting.

Contrary to our original hypotheses, the participants in the alternate-day fasting group did not experience more pronounced improvements in risk indicators for cardiovascular disease compared with the participants in the daily calorie restriction group. However, the trial included primarily metabolically healthy obese adults. Since many of the participants had normal cholesterol levels and normal blood pressure at baseline, it is not surprising that most risk indicators for cardiovascular disease did not change in response to diet.

Limitations

Our study has several limitations. First, the duration of the maintenance phase was short (6 months). Second, the control group was imperfect, in that they received no food, no counseling, and less attention from study personnel, relative to the intervention groups, which may have confounded our findings. We also failed to include the control group in our initial power calculation. Third, since the dropout rate was higher than anticipated, our power to detect the hypothesized difference of 5% weight loss between the intervention groups at month 6 decreased from 80% to 60%. The higher dropout rate in the alternate-day fasting group may have also introduced a possible selection bias between groups.27 Finally, we enrolled predominantly metabolically healthy obese individuals, which may have hindered the abilities of the interventions to produce greater improvements in our measured cardiovascular disease risk indicators.28,29 The generalizability of our findings is also limited by the enrollment.

Conclusions

The alternate-day fasting diet was not superior to the daily calorie restriction diet with regard to adherence, weight loss, weight maintenance, or improvement in risk indicators for cardiovascular disease.



Article Information

Corresponding Author: Krista A. Varady, PhD, Department of Kinesiology and Nutrition, University of Illinois at Chicago, 1919 W Taylor St, Room 532, Chicago, IL 60612 (varady@uic.edu).

Accepted for Publication: February 26, 2017.

Published Online: May 1, 2017. doi:10.1001/jamainternmed.2017.0936

Author Contributions: Dr Varady had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Drs Trepanowski and Kroeger contributed equally to this work and should be considered co–first authors.

Study concept and design: Kroeger, Varady.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Trepanowski, Kroeger, Varady.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Freels, Rigdon.

Obtained funding: Varady.

Administrative, technical, or material support: Kroeger, Barnosky, Bhutani, Hoddy, Gabel, Rood, Varady.

Study supervision: Varady.

Conflict of Interest Disclosures: Dr Varady reported receiving an advance for the book The Every-Other-Day Diet: The Diet That Lets You Eat All You Want (Half the Time) and Keep the Weight Off, published by Hachette Book Group. No other disclosures were reported.

Funding/Support: This study was supported by grant R01HL106228 from the National Institutes of Health/National Heart, Lung, and Blood Institute and grants P30DK072476 and F32DK107157 from the National Institute of Diabetes and Digestive and Kidney Diseases.

Role of Funder/Sponsor: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and the decision to submit the manuscript for publication

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