Intermittent Fasting: Dieting Magic or Fake News? (Show Notes from Episode 5)

The Quan Coaching Podcast Episode #5 – Intermittent Fasting: Dieting Magic or Fake News?

· Intermittent Fasting Introduction:

o Purported benefits in 2 large categories:

§ 1) Improving body composition/physique

§ 2) Improving clinical markers of disease

o So many different definitions of intermittent fasting

§ You’ll hear people talking about fasting for multiple days straight or fasting for 16 hours and it is all colloquially called “intermittent fasting”

o There has yet to be a firm conclusion based on the evidence as to which of these methods is best OR if any of them are superior to simply calorie restricting throughout the day every day

§ This is when it becomes very beneficial to actually look at the studies that have been done thus far since not a consensus conclusion

· I.e. it is not consensus like creatine’s positive effects

· To start this discussion, we need to actually define what intermittent fasting is. And there are 3 main categories/definitions of intermittent fasting:

o 1) Alternate-day fasting (ADF): eat normally for a day and then next day is “modified fasting” with 25% of total daily expenditure

o 2) Whole-day/5:2 fasting: 1-2 consecutive days per week of total fasting (or modified) and normal eating rest of week

o 3) Time-restricted feeding: feeding window (~4-8 hours) and a fasting window (~16-20 hours) which are the same each day

o

o Have different studies showing different effects so will need to treat all of these separately and talk about the effects and results of studies regarding each specific strategy

· Science and physiology behind the possible benefits of intermittent fasting (the following apply to all 3):

o A ton of mouse studies but no clear answer as to what the actual physiologic mechanism is

o A lot of the studying of fasting began due to Ramadan and observations made in this patient population regarding weight loss and potential health benefits so it was taken out of this sphere and turned into more scientific studies

o Upregulated autophagy = clean up process of the cell in which damaged organelles within the cell or misfolded proteins are broken down and recycled

§ This is where it was hypothesized that intermittent fasting may contribute to decreasing cancer risk because cancer is essentially unregulated growth of cells and autophagy can supposedly limit this

§ Decreased autophagy also associated with neurodegeneration, cardiovascular disease, infection

§ Can make metabolic processes more efficient which can result in better use of food for fuel and result in long term weight loss

o Prolonged fasting period may also cause greater use of free fatty acids for energy

o More mechanistic effects specifically for time restricted feeding that we will get into when discussing that, but lets first discuss the other 2 types

· Although little consensus on mechanisms, there have been a ton of clinical studies; although still no consensus on conclusions; thus, I think it will be very helpful to go through a lot of these studies for each of the 3 types of IF and talk about the results so we can arrive at our own conclusions

· 1) Alternate-day fasting (ADF): eat normally for a day and then next day is “modified fasting” with 25% of total daily expenditure

o More studied form than whole day fasting (TRF becoming more and more studied recently and has probably overtaken ADF over the past couple of years)

o Many studies compare this to eating normally (no calorie deficit at all) and then conclude that it allows for weight loss and improvement in metabolic parameters (lipid profile, fasting glucose, insulin sensitivity).

§ Health Effects of Alternate-Day Fasting in Adults: A Systematic Review and Meta-Analysis (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732631/)

§ This is fairly obvious in my opinion

§ More interesting and beneficial to compare to a diet that consumes the same amount of calories over a week long span but just does it by reducing the calories by a smaller amount each day

o “Modified alternate-day fasting vs. calorie restriction in the treatment of patients with metabolic syndrome: A randomized clinical trial” https://www.sciencedirect.com/science/article/abs/pii/S0965229919306570?via%3Dihub

§ 70 participants for 8 weeks; Alternate day fasting group with statistically significantly lower 1) body weight, 2) waist circumference, 3) systolic blood pressure, 4) fasting glucose; no difference in 1) triglycerides, 2) total cholesterol, 3) LDL, 4) HDL, 5) diastolic blood pressure, 6) fasting insulin

§ What we are going to start to see as a major theme is the real benefits of these intermittent fasting diets in those with metabolic syndrome

· Metabolic Syndrome = >=3 of the following and is characterized by a dysregulation of glucose and fat metabolism:

o Increased waist circumference (population based)

o Elevated fasting plasma glucose (>100 mg/dL or drug treated)

o Elevated blood pressure (>130/85 or drug treated)

o Hypertriglyceridemia (>150 mg/dL or drug treated)

o Reduced HDL (<40 mg/dL male, <50 mg/dL female, or drug treated)

· Significantly increased probability for those that are obese/overweight but not all who are obese/overweight have metabolic syndrome

o 33% of overweight individuals (BMI > 25) have metabolic syndrome

o 65% of obese individuals (BMI > 30) have metabolic syndrome

o The alternate-day fasting diet is a more effective approach than a calorie restriction diet on weight loss and hs-CRP levels (https://pubmed.ncbi.nlm.nih.gov/32003649/)

§ 80 total participants (with metabolic syndrome) for 4 months; Modified ADF vs calorie restriction = improved fat loss and more decrease in inflammatory markers

o Differential Effects of Alternate-Day Fasting Versus Daily Calorie Restriction on Insulin Resistance (https://pubmed.ncbi.nlm.nih.gov/31328895/)

§ Improved insulin sensitivity but no difference in weight loss in 43 participant, 12 month study. Other markers (blood pressure, lean mass, visceral fat, inflammatory markers, lipid profile) also did not change

o Now lets talk about normal weight individuals

o Effect of Alternate-Day Fasting on Weight Loss, Weight Maintenance, and Cardioprotection Among Metabolically Healthy Obese Adults: A Randomized Clinical Trial (https://pubmed.ncbi.nlm.nih.gov/28459931/)

§ No difference in weight loss in ADF with 25% on fast days compared to daily calorie restriction

§ No change in metabolic parameters

o “A randomized controlled trial to isolate the effects of fasting and energy restriction on weight loss and metabolic health in lean adults” https://www.science.org/doi/10.1126/scitranslmed.abd8034

§ Alternate day fasting with 0 calories on fasting days versus energy matched caloric deficit (25% decrease every day) in lean individuals. 3 week study with 12 participants in each group

· Same body weight loss, but more from fat-free mass in the alternate day fasting group

· ADF may be less effective in reducing fat mass than daily calorie restriction in lean individuals (although did not use 25% on fasting day)

o Other studies which ate 25% on fasting day did not lose muscle mass

o ADF Summary:

§ Could provide improved insulin sensitivity and possible improved fat loss for those with metabolic syndrome

§ Does not appear to improve lipid profile in any population

§ Likely no difference compared to a normal daily calorie restriction for those without metabolic syndrome and a non-modified ADF especially would not be a good idea for those who are already lean and trying to preserve muscle mass

· 2) Whole-day/5:2 fasting: 1-2 consecutive days per week of total fasting (or modified) and normal eating rest of week

o The effects of intermittent or continuous energy restriction on weight loss and metabolic disease risk markers: a randomized trial in young overweight women (https://pubmed.ncbi.nlm.nih.gov/20921964/)

§ No difference in weight loss or metabolic parameters

o Effect of Intermittent Compared With Continuous Energy Restricted Diet on Glycemic Control in Patients With Type 2 Diabetes (https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2688344)

§ Equivalent weight loss, fat free mass lost, fat loss, and HgbA1c decrease with 5:2 (modified) vs continuous daily restriction

o A randomised controlled trial of the 5:2 diet (https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0258853)

· Whole day fasting (5:2) was found to be safe and equivalent for weight loss compared to continuous daily calorie restriction

o Whole-Day/5:2 Summary:

§ Less clinical studies on this compared to alternate-day fasting

§ Equivalent to isocaloric weekly diet with daily calorie restriction in all categories

§ Less evidence compared to Alternate-day fasting in regards to improved insulin sensitivity and improved fat loss in those with metabolic syndrome

· If you have metabolic syndrome and/or are overweight or obese I would recommend ADF over 5:2

· 3) Time-restricted feeding (TRF): feeding window (~4-8 hours) and a fasting window (~16-20 hours) which are the same each day

o The scientific theories and basic science research behind TRF:

§ Biggest piece of underlying basic science is that TRF (specicially early TRF) allows eating to better align with circadian rhythms (24 hour cycle) in metabolism

· Suprachiasmatic nucleus of the hypothalamus is the “clock” which organizes the circadian control of energy intake.

o Synchronizes to light-dark cycle and to other secondary “clocks” in other areas of the brain

o Controls rhythms in central metabolic hormones (think cortisol, melatonin, adipokines, ghrelin), circulating nutrients, and neural inputs that tell peripheral organs when to anticipate feeding and fasting periods and prime metabolic responses appropriately

§ For instance, melatonin influences the synthesis and secretion and action of insulin therefore is a major player in insulin sensitivity and glucose homeostasis

§ Enzymes responsible for carbohydrate and fat breakdown and storage are upregulated at certain parts of the day in anticipation of feeding windows

· By eating outside of circadian rhythms, basic science research has shown that increased inflammation and aberrant hormonal and glucose homeostasis occurs as there is reciprocal regulation between the circadian clock and nutrient metabolism

o Likewise, erratic eating patterns as well as other behaviors that disrupt circadian rhythms (shift work, sleep deprivation, etc) can increase risk of metabolic syndrome, cardiovascular disease, and cause progressive aging (rat studies)

· Specifically, studies have shown that our bodies enzymes and metabolic processes responsible for breaking down our food for fuel and storage, are most active in the morning

o Demonstrated in basic science studies as well as clinical studies that demonstrate improved weight loss when eating more calories in morning compared to night

· One study also demonstrated that TRF allows for the restoration of diurnal variation of bacteria in the gut microbiome which protect against metabolic consequence of obesity

§ Also has the potential effect of upregulated autophagy and free fatty acid use

o There has therefore been a lot of basic science research demonstrating possible practical effects of TRF; however, we need to look to the more practical clinical research to see if these effects actually exist and if they do, for what population of people?

o Effects of eight weeks of time-restricted feeding (16/8) on basal metabolism, maximal strength, body composition, inflammation, and cardiovascular risk factors in resistance-trained males (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5064803/)

§ 34 male participants for 8 weeks. Normal diet vs 16/8 delayed TRF (1-8pm)

§ TRF = 1.5kg fat loss with no fat-free mass loss or strength loss

§ Decreased glucose and insulin

§ marginally decreased inflammatory markers

§ decreased anabolic hormones (testosterone and IGF-1)

§ No changes in lipid profile

o Time-restricted feeding plus resistance training in active females: a randomized trial (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6735806/)

§ 24 female participants for 8 weeks. Normal vs 16/8 (1200-2000)

§ Decrease in fat mass in TRF group, not in normal

§ Fat free mass and strength metrics same between groups

§ No difference in metabolic parameters (glucose, insulin, cortisol, blood pressure, RMR, etc)

o Time-restricted feeding improves markers of cardiometabolic health in physically active college-age men: a 4-week randomized pre-post pilot study (https://www.sciencedirect.com/science/article/abs/pii/S0271531719305536?via%3Dihub)

§ Reduced body fat, blood pressure, and increases in HDL

o A controlled trial of reduced meal frequency without caloric restriction in healthy, normal-weight, middle-aged adults (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2645638/)

§ Small crossover study of 15 people for 8 weeks which demonstrated loss of fat mass (2kg) with TRF (1 meal per day) without caloric restriction vs no loss with 3 meals/day with little change to other metabolic markers

o Early Time-Restricted Feeding Reduces Appetite and Increases Fat Oxidation but Does Not Affect Energy Expenditure in Humans (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6658129/)

§ Small study (11 overweight participants in intervention group) that demonstrated no difference in energy expenditure between groups (one hypothesized cause for cause of being able to reduce body weight) but found a decreased appetite (decreased ghrelin and increase in satiety hormone PYY)

o High Caloric intake at breakfast vs. dinner differentially influences weight loss of overweight and obese women (https://onlinelibrary.wiley.com/doi/10.1002/oby.20460)

§ About 80 overweight/obese women with metabolic syndrome. Ate 700kcals for breakfast, 500 lunch, 200 breakfast versus 200 breakfast, 500 lunch, 700 dinner

§ At 12 weeks, the large breakfast group had a 11% decrease in weight compared to 4% in dinner group and 8% decrease in waist circumference compared to 3% in dinner group.

§ Lipid panel, glucose, insulin, ghrelin, and insulin sensitivity were all also improved in the group eating the large breakfast

o Time-Restricted Eating and Metabolic Syndrome: Current Status and Future Perspectives (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828812/#B103-nutrients-13-00221)

§ Review of TRF studies specifically in patients with metabolic syndrome

§ 3-4% decrease in weight/fat mass/waist circumference with TRF in those at risk for metabolic syndrome (4 and 6 hour feeding windows were equivalent)

§ Decrease in caloric intake by ~9-20% when TRF implemented with no recommendations to change total caloric intake

· Aligns with study demonstrating decreased ghrelin/subjective appetite scores

§ Glucose metabolism (HgbA1c, insulin sensitivity, fasting plasma glucose) appears to be more influenced in those with metabolic syndrome compared to healthy individuals

§ Fairly consistent that lipid panel changes not significant in those with normal lipids at baseline

· Some studies demonstrating ~10% decrease in LDL and total cholesterol and others with no effect

§ Up to 4-8% BP decrease although results mixed (about 50-50 on whether the study showed a decrease here (only in obese/overweight/metabolic syndrome)

§ Safe even with 4-6 hour feeding windows with no real adverse effects especially after adjustment period

§ Some data to suggest that shorter feeding windows are better, but this decreases long term adherence. 8-10 hour feeding windows may be a good happy medium for desired effects and adherence

§ More studies needed to do the following:

· Larger RCTs to find true effects over the long term

· Better understand mechanism

· Find best protocol (feeding window time, early vs late, etc.)

o Time-Restricted Feeding Summary:

§ Only IF protocol that has been shown more times than not to best continuous caloric restriction in terms of fat loss in healthy individuals

§ Likely most beneficial for those with metabolic syndrome in regards to metabolic markers (glucose and insulin regulation appear promising)

§ Allows for decreased appetite over the long term and decreased energy intake with fairly good adherence during the studies

§ Shorter feeding windows likely better, but do what you can adhere to

· Overall summary of IF:

o A lot more research needs to be done to draw consensus conclusions

o From the research available it appears that TRF has the most promise, especially for already healthy individuals

o Is it easier for you to do intermittent fasting in order to arrive at a calorie deficit goal over a week long period? Or is it easier for you to restrict calories by the same amount each day? This is why this is partially an individualized process based in large part on your psychology

o The best diet is the one that you can keep to over the long term

§ Adherence was shown to be better in the daily calorie restricted group (26% drop out) of this study compared to alternate day fasting (38% drop out; also less likely to meet calorie goals)

· Effect of Alternate-Day Fasting on Weight Loss, Weight Maintenance, and Cardioprotection Among Metabolically Healthy Obese Adults: A Randomized Clinical Trial (https://pubmed.ncbi.nlm.nih.gov/28459931/)

§ Give it a try. Studies have shown that it is safe and does not result in rebound weight gain

· A randomized pilot study comparing zero-calorie alternate-day fasting to daily caloric restriction in adults with obesity (https://pubmed.ncbi.nlm.nih.gov/27569118/)

o No adverse effects, 93% completed 8 week study, no extra rebound weight gain compared to daily calorie restriction group

· A randomised controlled trial of the 5:2 diet (https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0258853)

o Whole day fasting (5:2) was found to be safe and equivalent for weight loss compared to continuous daily calorie restriction

· Same with TRF