Intermittent Fasting and Time Restricted Fasting in Humans

We hear so much about the benefits of intermittent fasting (increased life span, weight loss, autophagy, normalization of lab values like insulin/fasting glucose/cholesterol, etc), but who were these studies done on and do they relate to the general population? I’ve been fascinated by the claims of intermittent fasting for awhile, so decided to really dig my heals into the research that was available. But rather than survey the entirety of literature available on the subject (a seemingly impossible task), I went in with a specific lens.

INTRO

When doing any sort of research, you typically enter into it with primary and secondary questions. My primary question was “is intermittent fasting effective and what are its benefits, particularly for human women?” HAHA human women, as if there is another kind of woman. I make this distinction because A TON of intermittent fasting research is done on mice/rats, making it difficult to discern if the results would be clinically relevant to human humans.

So while there is benefits to the data that’s been presented on rats / animals, for the sake of my own research, I limited the studies I looked at to humans.

As I continued to sift through the (very dense) research, some more questions arose:

  1. Is the research done on peri/menopausal women
  2. Is there a difference between intermittent fasting in overweight adults vs non-overweight adults
  3. What are the various definitions of intermittent fasting and do they all yield the same results
  4. Are there clinically significant changes in common lab values: cholesterol, A1C, insulin, blood pressure, etc
  5. Are there compensatory behaviors and/or negative mood implications following intermittent fasting? I group this into a “emotional” results of a study.
  6. If there are positive benefits, do they last longer than the study?

So these are the questions that went into my research. I used systematic review studies, randomized, control studies as well as anecdotal research. While I aim to provide the most current evidence based research, I also value “citizen science.” They both play a role in decision making and both have validity, especially when there are limited evidence based studies on what I’m researching.

A lot of the studies on intermittent fasting are done on vastly different populations. In order to instill some small semblance of organization, I’ve organized them based on overall purpose and population. After each category, I’ll briefly summarize the main takeaways, relevant to that specific population base. With larger, sweeping generalizations at the end of the post.

To begin, many of the studies distinguish between overweight populations vs “normal” weight populations. Obviously not the best language, but for the sake of simplicity and paralleling the vernacular of the studies, that’s what I’ll stick with here.

INTERMITTENT FASTING IN OVERWEIGHT POPULATIONS

Physical benefits

Alternate day fasting

  • beneficial reductions in serum cholesterol and triglycerides, markers of oxidative stress and asthma inflammatory markers (modified alternate day fasting in overweight adults with asthma for 8 weeks) (1)
  • weight loss and decreases in several key biomarkers for CAD risk, such as total cholesterol, LDL cholesterol, triacylglycerols, systolic blood pressure, and heart rate, were also observed. (8 weeks modified alternate day fasting in adults) ( 3 )
  • relative (%) weight loss was greater in the alternate day fasting group at the end of the 8-week intervention, though this difference wasonly marginally significant and may be driven by the differences in baseline body weight between groups (8 weeks zero calorie alternate day fasting in obese adults) ( 4 )
  • alternate day fasting induces long-term changes in BDNF secretion, which may contribute to improved weight loss maintenance through effects on energy balance (8 weeks zero calorie alternate day fasting in obese adults) ( 4 )
  • Resting metabolic rate (RMR) decreased significantly in caloric restriction but not in alternate day fasting over the 8-week intervention (8 weeks zero calorie alternate day fasting in obese adults) ( 4 )
  • Intermittent fasting, alternate day fasting, and caloric restriction regimens appear to be effective for reducing body weight, although caloric restriction may result in slightly greater weight loss. As forvisceral fat mass, and fasting insulin and insulin sensitivity, the effect of intermittent fasting, alternate day fasting, and caloric restriction on these diabetic risk parameters appears comparable (systematic review of human findings for intermittent fasting vs daily caloric restriction for Type 2 diabetes in overweight adults) ( 18 )

In low calorie diet (30% of daily needs for 6 days) + 1 day of fasting per week (<150cal / day) for 8 weeks

  • decreased key indicators of CHD risk, such as LDL cholesterol, triglycerides, and the proportion of small LDL particles in both groups (liquid or food-based 30% calorie restriction x6days + <150cal x1 day in for 8 weeks in obese women) ( 5 )

5:2 fasting in overweight women vs overall calorie restriction (3-6 months)

  • Both groups experienced comparable reductions in body fat, FFM, hip, bust and thigh circumference and composition of weight loss. Percentage of weight lost which was fat in the intermittent energy restriction and continuous energy restriction groups was 79% in both groups (25% caloric restriction all days vs 75% restriction on 2 consecutive days in obese young women for 6 months) ( 6 )
  • Both groups experienced modest declines in fasting serum insulin and improvements in insulin sensitivity which were greater amongst the intermittent energy restriction group (25% caloric restriction all days vs 75% restriction on 2 consecutive days in obese young women for 6 months) ( 6 )
  • Both diets led to comparable reductions in total and LDL cholesterol, triglycerides, systolic and diastolic BP. Neither group experienced changes in HDL levels (25% caloric restriction all days vs 75% restriction on 2 consecutive days in obese young women for 6 months) ( 6 )
  • Intermittent energy and carbohydrate restriction diet is superior to the daily energy restriction diet with respect to the improvements in insulin sensitivity and the loss of body fat (daily caloric restriction vs 70% restriction on 2 consecutive days in overweight women) ( 2 )

Emotional backlash?

  • similar rate of weight loss was achieved during the ADF controlled food intake period when compared with the alternate day fasting self-selected food intake period. data suggest that subjects were able to maintain the alternate day fasting meal pattern when preparing their own meals at home (ie, when removed from a clinically controlled environment), indicating no promotion of binging tendencies (8 weeks of modified ADF in obese adults) ( 3 )
  • The study reports compliance issues, as some report hunger with IF and difficulty maintaining daily living activities during restricted days (8 weeks zero calorie alternate day fasting in obese adults) ( 4 )
  • small number of the intermittent fasting group but none of the calorie restriction group experienced minor adverse physical symptoms including lack of energy, headaches, feeling cold, feeling hungry, lack of concentration, bad temper, preoccupation with food, and constipation. 32% of the intermittent energy restriction and 46% of the continual energy restriction group reported increased self confidence and positive mood.More of the IER group reported problems fitting the diet into daily routine (25% caloric restriction all days vs 75% restriction on 2 consecutive days in obese young women for 6 months) ( 6 )
  • intermittent fasting does not appear to lead to compensatory over-consumption on the non-dieting days in any of the trials. (daily caloric restriction vs 70% restriction on 2 consecutive days in overweight women) ( 2 )
  • symptoms such as feeling cold, decreased energy levels, constipation, headaches, bad breath on energy-restricted, feeling light-headed, lack of concentration, mood swings or bad temper, and being preoccupied with food were evident in the modified alternate day fasting group (daily caloric restriction vs 70% restriction on 2 consecutive days in overweight women) ( 2 )
  • Average weekly hunger scores did not differ between groups throughout the study. At 1 month, hunger and desire-to-eat scores were marginally greater after the first restricted day of intermittent energy and carbohydrate restriction compared with the first restricted day of intermittent energy and carbohydrate restriction + protein and fat consumption and an average daily energy restriction day. This difference was no longer evident after 3 and 4 months, indicating that women had become used to the restriction (daily caloric restriction vs 70% restriction on 2 consecutive days in overweight women) ( 2 )
  • the success of both intermittent energy and carbohydrate restriction diets is not only linked to the adherence to the 2 d restriction, but is also attributable to the spontaneous restriction of energy and carbohydrate on non-restricted days. Intakes on these days in the intermittent energy and carbohydrate restriction groups were comparable with those of the daily energy restriction group. This is an important observation and confirms the present data and the data of others which show that intermittent dieting does not lead to disordered eating and overconsumption on non-restricted day (daily caloric restriction vs 70% restriction on 2 consecutive days in overweight women) ( 2 )

Long-term implications / sustainability?

  • participants were able to maintain weight loss when they self-selected food intake during the last 4 weeks of the study (8 weeks of modified alternate day fasting in obese adults) ( 3 )
  • individuals who did alternate day fasting kept the weight off after 6 months more than the caloric energy restriction group (8 weeks of zero calorie alternate day fasting in obese adults) ( 4 )
  • During the 24-week follow-up, alternate day fasting lost fat mass and gained lean muscle while caloric restriction gained both fat mass and lean muscle (8 weeks of zero calorie alternate day fasting in obese adults)( 4 )
  • 1 d of restriction per week maintained weight loss and the reductions in disease risk markers in the short term, similarly to the daily energy restriction group who were asked to have the recalculated euenergetic daily energy restriction (daily caloric restriction vs 70% restriction on 2 consecutive days in overweight women) ( 2 )
  • Labs: Reductions in insulin resistance, weight, adiposity, circumferences, leptin, IL-6 and lipids were maintained during the final weight maintenance month in all groups (intermittent fasting, intermittent fasting + ad libitum fat/protein consumption, and caloric restriction) (daily caloric restriction vs 70% restriction on 2 consecutive days in overweight women) ( 2 )

To re-cap:

  • Intermittent fasting (as defined by alternate day fasting, or periods of extended, significant decreased caloric intake), may be beneficial in overweight populations in regards to: weight loss, blood pressure, serum cholesterol, triglycerides, certain inflammatory markers present in asthmatics (reduction in serum TNFα, BDNF, and ceramides), fasting serum insulin and insulin sensitivity, and BDNF secretion. Intermittent fasting also didn’t result in changes in resting metabolic rate, whereas prolonged caloric / energy restriction did.
  • In regards to individuals with Type 2 Diabetes Mellitus, prolonged caloric restriction seems to have the same benefits as intermittent or alternate day fasting.
  • More research needs to elucidate if these results are specific to intermittent fasting, or if they are similar across any program which improves insulin sensitivities. One study, for example, revealed that “reductions in insulin resistance, weight, adiposity, circumferences, leptin, IL-6 and lipids were maintained during the final weight maintenance month in all groups (intermittent fasting, intermittent fasting + ad libitum fat/protein consumption, and caloric restriction)” in a study that examined daily caloric restriction vs 70% restriction on 2 consecutive days in overweight women. ( 2 )
  • While intermittent fasting doesn’t seem to lead to any severe adverse events or compensatory over-consumption eating behaviors, some participants did report mild adverse events which calls into question the long-term efficacy and compliance of such a diet. Though this was done in zero calorie alternate day fasting. These adverse events did not ring true with a modified alternate day fasting regimen.
  • There do seem to be long-term benefits for this patient population, as those who performed alternate day fasting for 8 weeks had lost fat mass and gained lean muscle while caloric restriction gained both fat mass and lean muscle, even 6 months after the study was performed (8 weeks of zero calorie alternate day fasting in obese adults)( 4 )

INTERMITTENT FASTING IN NON-OVERWEIGHT POPULATIONS

Physical benefits

Alternate day fasting

  • women had significantly lower glucose, insulin, free fatty acid, triacylglycerol, and LDL-cholesterol concentrations and significantly higher HDL-cholesterol and ghrelin concentrations than did the men (zero calorie alternate day fasting in non-obese men and women for 3 weeks) ( 7 )
  • Fasting glucose, ghrelin (hunger hormone), resting metabolic rate, systolic, and diastolic blood pressure, were not significantly changed from baseline in the men or the women. Fasting insulin was lower on day 22 in both the men and the women (zero calorie alternate day fasting in non-obese men and women for 3 weeks) (  7 )
  • the subjects lost 2.5 ± 0.5% of their initial body weight; fat oxidation was increased and translated into fat mass loss (zero calorie alternate day fasting in non-obese men and women for 3 weeks) ( 7 )

Fasting mimicking diets (FMD):

  • In the fasting mimicking diet subjects, fasting blood glucose levels were reduced by and remained lower than baseline levels after resuming the normal diet following the third FMD cycle (FMD eating ~700 calories for 5 days per month for 3 months in healthy adults) (17 )
  • CRP levels were reduced by the FMD cycles. 8 of the 19 fasting mimicking diet subjects had CRP levels in the moderate or high cardiovascular disease risk range at baseline. For 7 of them, the levels returned to the normal range after 3 FMD cycles (FMD eating ~700 calories for 5 days per month for 3 months in healthy adults) (17 )
  • The FMD resulted in a 3% reduction in body weight that remained lower at the completion of the study. Fat loss accounted for most of the weight loss. Pelvis bone mineral density was not affected by the fasting mimicking diet (FMD eating ~700 calories for 5 days per month for 3 months in healthy adults) (17 )

Prolonged fasting:

  • Improvements with rheumatoid arthritis symptoms if followed by a vegetarian / vegan diet (adults with RA who fasted 7-10 days followed by vegan or vegetarian diet for 3-3.5 months) ( 19 )
  • significant increase in discrete growth hormone pulse frequency in males (a medically supervised 5 day fast in 6 men of healthy body weight and BMI) (2 day fast in 9 normal weight men) ( 23,  24 )

Emotional backlash + long-term implications?

  • In alternate day fasting: prolonged schedule of fasting and feasting would be marred by aversive subjective states (eg, hunger and irritability), which would likely limit the ability of most individuals to sustain this eating pattern. Hunger on fasting days did not habituate over the course of the study, which perhaps indicates the unlikelihood of subjects continuing on this diet for extended periods of time. (zero calorie alternate day fasting in non-obese men and women for 3 weeks) ( 7 )
  • Adverse effects were higher after completion of the first fasting mimicking diet cycle compared to those during the second and third fasting mimicking diet cycles. However, the average reported severity of the side effects was very low and below “mild” (<1 on a scale of 1–5). (FMD eating ~700 calories for 5 days per month for 3 months in healthy adults) (17 )
  • Averse impacts on mood and perceived work performance, not through hunger or physiological deprivation, but through an increased cognitive load as a result of an increased attention toward food as a result of dieting/fasting (2 consecutive days of <500cal/day eating in non-obese young women for 2 days) ( 8 )
  • poorer positive mood and poorer perceived work performance on fast days compared to non-fast days were associated with higher distraction, as opposed to the act of fasting or higher hunger (2 consecutive days of <500cal/day eating in non-obese young women for 2 days) ( 8 )
  • intermittent fasting offers no benefits for mood or perceived work performance over traditional dieting as a result of reduced distraction during fast days in young, lean women (2 consecutive days of <500cal/day eating in non-obese young women for 2 days) ( 8 )

To re-cap:

  • In non-overweight adults doing alternate day fasting, both men and women had lower glucose, insulin, free fatty acid, triacylglycerol, and LDL-cholesterol concentrations and significantly higher HDL-cholesterol and ghrelin concentrations (women > men). Both men and women experienced weight loss. Fasting glucose, ghrelin, resting metabolic rate, systolic, and diastolic blood pressure was not significantly changed from baseline in the men or the women ( 7 )
  • In fasting mimicking diets, individuals experienced reduced fasting blood glucose levels, weight loss (with fat loss making up most of the weight loss), and a normalization of certain inflammatory markers (CRP) ) (17 ).
  • Despite positive lab values, individuals who were not overweight experienced some aversive states like hunger and irritability (though this was done in zero calorie alternate day fasting, and results may be different with a more mild or modified version). There was also a significant negative effect on work performance in young, lean women who underwent two days of consecutive fasting (this study was quite short and the two days of consecutive fasting consisted of nearly no energy consumption at all – results may have varied with a more modified version of fasting). Results may have varied with a modified alternate day or consecutive 2-day fast ( 8 ).

IF in COMBINED OVERWEIGHT AND NON-OVERWEIGHT SUBJECTS

Physical effects:

Fasting mimicking diet:

  • Participants in the fasting mimicking diet lost on average 2.6 ± 2.5 kg of weight, which was due in part to a reduction in total body fat and trunk fat. Subjects on the control diet did not lose body weight. No change in the percentage of lean body mass was observed (in both overweight and non-overweight adults who underwent 5, ~700kcal/day consecutive days of fasting per month for 3 months vs no change control diet) ( 33 )
  • In subjects who completed three fasting mimicking diet cycles and who returned to the normal diet for 5 to 7 days, body weight, BMI, total body fat, trunk fat, absolute lean body mass, waist circumference, IGF-1, systolic and diastolic blood pressure, total cholesterol, LDL, and HDL were significantly reduced, and relative lean body was increased. Fasting glucose, β-hydroxybutyrate, triglycerides, and CRP were not significantly changed. ( 33 )
  • fasting mimicking diet was particularly beneficial among subjects who were obese (BMI >30) at baseline. The fasting mimicking diet-dependent reduction in IGF-1 was also larger in participants with baseline higher IGF-1 (in both overweight and non-overweight adults who underwent 5 consecutive days of fasting ~700cal per month for 3 months vs no change control diet) ( 33 )

Emotional back-lash:

  • participants reported no adverse effects during the fasting mimicking diet The most common self-reported grade 1 (mild) or grade 2 (moderate) symptoms experienced by the participants were fatigue, weakness, and headaches. No adverse effects of grade 3 or higher were reported. Note that 25% of the subjects who tested the FMD dropped out of the trial, whereas 10% of the participants opted out of the control arm. This indicates that, despite our efforts to reduce the burden of low-calorie/protein diets, adherence to this dietary regimen requires committed study participants (in both overweight and non-overweight adults who underwent 5 consecutive days of fasting ~700cal per month for 3 months vs no change control diet) ( 33 )

To recap:

  • in fasting mimicking diets, individuals who were both normal weight and overweight experienced reduced body weight, BMI, total body fat, trunk fat, absolute lean body mass, waist circumference, IGF-1, systolic and diastolic blood pressure, total cholesterol, LDL, HDL, and relative lean body was increased. Fasting glucose, β-hydroxybutyrate, triglycerides, and CRP were not significantly changed.
  • Mild adverse effects were reported, such as fatigue, weakness, and headaches. ( 33 )

TIME RESTRICTED FEEDING IN OVERWEIGHT POPULATIONS

***many studies are not specifically time restricted feeding, but instead are studies “skipping breakfast.” These studies are inherently biased, as they don’t offer a firm cut-off point for eating at night.

Physical:

  • resting metabolic rate was stable from baseline to follow-up, with no difference between groups in response to the intervention (daily breakfast consumption vs extended morning fasting in obese adults for 6 weeks) ( 11 )
  • Thyroid hormones that regulate resting metabolic rate were unresponsive to either treatment, with systemic concentrations of triiodothyronine (free-T3) and thyroxine (free-T4) closely matched between treatments at baseline and follow-up(daily breakfast consumption vs extended morning fasting in obese adults for 6 weeks) ( 11 )
  • range of hormones implicated in the regulation of appetite and energy balance also did not differ in response between treatments (leptin, total ghrelin, acylated ghrelin, peptide YY, active glucagon-like peptide-1, and adiponectin) (daily breakfast consumption vs extended morning fasting in obese adults for 6 weeks) ( 11 )
  • glycemic response to the oral glucose tolerance test was unaffected by either intervention (daily breakfast consumption vs extended morning fasting in obese adults for 6 weeks) ( 11 )
  • 1) no difference in reported total energy intake between interventions, indicative that those fasting during the morning at least partially compensated for the ≥700 kcal deficit imposed;2) lower physical activity thermogenesis in those fasting before 1200 than in those who consumed breakfast; 3) similar blood lipid, appetite regulatory hormone, and C-reactive protein responses to the intervention between groups but with a decreased insulinemic response to an OGTT in those consuming breakfast relative to an increase in those extending their fast; and 4) no evidence that the omission of breakfast had any effect on body weight. (daily breakfast consumption vs extended morning fasting in obese adults for 6 weeks)( 11 )
  • eating breakfast helped reduce dietary fat and minimize impulsive snacking and therefore may be an important part of a weight-reduction program. This was an older study that also didn’t put a time limit on last meal of the day, so it’s not true intermittent fasting in nature (eating vs omitting breakfast in obese women for 12 weeks) ( 14 )
  • Although 5 weeks of evening time restricted fast did not improve glucose levels, it dramatically lowered insulin levels and improved insulin sensitivity and β cell responsiveness. (restricting feeding from 7am-3pm in pre-diabetic males for 5 weeks) ( 34 )
  • the reductions in insulin levels were largest in participants with worse hyperinsulinemia at baseline (restricting feeding from 7am-3pm in pre-diabetic males for 5 weeks)  ( 34 )
  • the one participant whose insulin levels worsened on evening time restricted fast had reported a long history of overnight shift work prior to enrolling in the trial. Given that circadian rhythms are altered in adults who perform overnight shift work, it will be important to determine whether some subpopulations have altered circadian rhythms and would benefit more from alternative meal timing interventions. ( 34 )
  • evening time restricted fast did not affect HDL cholesterol or LDL cholesterol, though did increase morning fasting levels of triglycerides (restricting feeding from 7am-3pm in pre-diabetic males for 5 weeks) ( 34 )
  • evening time restricted fast dramatically lowered systolic and diastolic blood pressure by 11 and 10 mmHg on average, which is similar to anti-hypertensive medications (restricting feeding from 7am-3pm in pre-diabetic males for 5 weeks) ( 34 )
  • evening time restricted fast did not affect morning fasting levels of the hunger hormone ghrelin (restricting feeding from 7am-3pm in pre-diabetic males for 5 weeks) ( 34 )
  • improvements in blood pressure and oxidative stress levels (f8-isoprostane, a marker of oxidative stress to lipids (restricting feeding from 7am-3pm in pre-diabetic males for 5 weeks) ( 34 )

Emotional: 

  • evening time restricted fast substantially reduced the desire to eat and the capacity to eat in the evening and non-significantly decreased hunger levels. It also increased sensations of fullness in the evening and nearly significantly increased sensations of a full stomach (restricting feeding from 7am-3pm in pre-diabetic males for 5 weeks) ( 34 )

To recap:

  • In overweight women, RMR, thyroid hormones (TSH, free T3 and free T4), appetite hormones (leptin, total ghrelin, acylated ghrelin, peptide YY, active glucagon-like peptide-1, and adiponectin), and glycemic response, were stable and unchanged between eating and omitting breakfast
  • in women, there was reduced body mass in groups that omitted breakfast, though this wasn’t in a true intermittent fasting study. Participants were permitted to eat throughout the evening with no firm cut-off for feeding times.
  • in women, eating breakfast helped reduce dietary fat and minimize impulsive snacking throughout the day, though this wasn’t in a true intermittent fasting study. Participants were permitted to eat throughout the evening with no firm cut-off for feeding times.
  • In pre-diabetic men, evening time restricted feeding (eating only from 7am-3pm), reduced insulin levels and improved insulin sensitivity. It also lowered blood pressure just as effectively as anti-hypertensive medications. It did not affect hunger hormone ghrelin. It also did not affect weight loss. It further increased sensations of fullness in the evening. It did, however, increase morning levels of triglycerides.

 

TIME RESTRICTED FEEDING IN NON-OVERWEIGHT POPULATIONS

***many studies are not specifically time restricted feeding, but instead are studies “skipping breakfast.” These studies are inherently biased, as they don’t offer a firm cut-off point for eating at night.

Physical:

  • 2 weeks of nighttime energy restriction resulted in a significant difference in energy intake and body weight in healthy young men (11 hours of nightly energy restriction in young, non-obese men) ( 9 )
  • Subjects consuming 1 meal/d exhibited higher morning fasting plasma glucose levels, greater and more sustained elevations of plasma glucose concentrations, poorer glucose tolerance, and a delayed insulin response in the OGTT compared to subjects consuming 3 meal/d. The meal, however, was consumed close to bed time and lab values were drawn in the early morning, which could have negatively impacted results. (normal weight adults consuming 1 meal per day in 4 hour time period or 3 meals per day throughout the day for 8 weeks) ( 10 )
  • consumption of one unusually large meal per day worsens morning glucose tolerance compared to an isocaloric diet spread across three meals. However, when on 1 meal/d the subjects would have eaten less than those on 3 meals/day if we had not asked them to consume the same amount of food that they normally eat on a 3 meal/d schedule. The meal, however, was consumed close to bed time and lab values were drawn in the early morning, which could have negatively impacted results. (normal weight adults consuming 1 meal per day in 4 hour time period or 3 meals per day throughout the day for 8 weeks) ( 10 )
  • fasting plasma insulin concentrations were not significantly affected by meal frequency and there were no significant effects of diet on insulin responses to glucose during the OGTT. The meal, however, was consumed close to bed time and lab values were drawn in the early morning, which could have negatively impacted results. (normal weight adults consuming 1 meal per day in 4 hour time period or 3 meals per day throughout the day for 8 weeks) (10)
  • when on 1 meal/d, subjects exhibited: a significant reduction of fat mass, and significant increases in levels of total and LDL and HDL cholesterol (normal weight adults consuming 1 meal per day in 4 hour time period or 3 meals per day throughout the day for 8 weeks) ( 10 )
  • there were no significant effects of meal frequency on plasma levels of ghrelin, adiponectin, resistin or BDNF (normal weight adults consuming 1 meal per day in 4 hour time period or 3 meals per day throughout the day for 8 weeks) ( 10 )
  • omitting breakfast impairs fasting lipids and postprandial insulin sensitivity and could lead to weight gain if the observed higher energy intake was sustained. This study, however, allowed participants to eat up until 9pm. There was no hard cut off for limiting feeding period in the evenings. (eating breakfast vs omitting breakfast in healthy, lean women for 6 weeks ( 13 )
  • in healthy lean women, omitting breakfast led to a higher plasma total and LDL-cholesterol concentrations and lower postprandial insulin sensitivity than did EB. Mean reported total EI was significantly lower during the EB period than during the OB period. This study, however, allowed participants to eat up until 9pm. There was no hard cut off for limiting feeding period in the evenings. (eating breakfast vs omitting breakfast in healthy, lean women for 6 weeks ( 13 )
  • plasma total and LDL-cholesterol concentrations increased after the OB period more than they did after the EB period. Fasting plasma HDL-cholesterol and triacylglycerol concentrations, however, showed no significant differences between the EB and OB periods (eating breakfast vs omitting breakfast in healthy, lean women for 6 weeks). This study, however, allowed participants to eat up until 9pm. There was no hard cut off for limiting feed period in the evenings. (13)
  • Body weight did not differ significantly between the pre-intervention and post-intervention periods. This study, however, allowed participants to eat up until 9pm. There was no hard cut off for limiting feed period in the evenings. (eating breakfast vs omitting breakfast in healthy, lean women for 6 weeks) ( 13 )
  • No significant changes were observed in serum total cholesterol, triglycerides and LDL levels. TC/HDL ratio (HDL risk factor) was decreased during and after Ramadan in both genders in the fasting group while there were no changes in the non-fasting group (healthy weight adults who fasted from sunrise until sunset for 30 days) ( 25 )
  • IL-6, CRP, and homocysteine levels were significantly low during Ramadan in the fasting subjects of both genders when compared to basal values (1 week before Ramadan) (healthy weight adults who fasted from sunrise until sunset for 30 days). ( 25 )
  • decrease in fat mass in time restricted fasting compared to normal diet, while fat-free mass, muscle area of the arm and thigh, and maximal strength were maintained in both groups. Testosterone and insulin-like growth factor 1 decreased significantly in TRF, with no changes in ND. Adiponectin increased in time restricted fasting while total leptin decreased, although not when adjusted for fat mass. Triiodothyronine decreased in time restricted fasting, but no significant changes were detected in thyroid-stimulating hormone, total cholesterol, high-density lipoprotein, low-density lipoprotein, or triglycerides. Resting energy expenditure was unchanged, but a significant decrease in respiratory ratio was observed in the time restricted fasting group (16/8 hour time restricted fasting in young, healthy men for 8 weeks) ( 29 )
  • intermittent fasting program in which all calories are consumed in an 8-h window each day, in conjunction with resistance training, could improve some health-related biomarkers, decrease fat mass, and maintain muscle mass in resistance-trained males (16/8 hour time restricted fasting in young, healthy men for 8 weeks) ( 29 )
  • no significant differences between groups in fat-free mass, indicating that the influence of nutrient timing may be negligible when the overall content of the diet is similar (16/8 hour time restricted fasting in young, healthy men for 8 weeks) ( 29 )
  • even though androgen concentrations were lowered by time restricted fasting, there was no difference in muscle mass changes between groups (16/8 hour time restricted fasting in young, healthy men for 8 weeks) ( 29 )

Emotional:

  • Mood was assessed using the Profile of Mood States (POMS) scale at the beginning and end of each condition. There was no pre/post-change for total mood score or its sub- scales within the nightly energy restriction and control conditions (11 hours of nightly energy restriction in young, non-obese men)  ( 9 )
  • “never been leaner in my life! You still eat 3 meals a day just within that 8hr timeline. So much energy. So much! If I eat outside the timeline (if I’m starving in the morning), it should be whole fruit and only fruit, as it takes 30 minutes to digest. Also extremely convenient, as there’s no time at work to eat breakfast anything. Definitely a decrease in the amount of bloating I feel as well.” – female reader submission
  • “I have done IF fasting for the 8 hours eating window, 16 hour fasting window. I have my bulletproof coffee during my fasting window, but otherwise only consume water during that time. I often find it makes me feel shaky and sick 50% of the time when I fast.” – female reader submission
  • “I did IF for over a year 12pm-8pm eating window 6-7 days a week. Was easy at first but actually became harder with time, eventually was starving by 11am, then 10am. Fiddled with eating hours to try to make it work. After major life upheaval event 7 months ago, I gave it up completely, went back to just eating when I feel hungry. Sometimes that’s right when I get up, sometimes it’s not until 1pm. I do still try to cut off food by 8pm. During year of strict fasting, I can’t say I saw any notable changes. Most notably: no weight loss.” – female reader submission
  • “I’ve been dabbling in IF for about 3 months now, and have honestly found it super helpful for my gut. I have a lot of digestive issues and following a 16/8 has reduced my bloating and constipation immensely. That said, I have hypothyroidism and no period so I haven’t shared publicly because I know it has a lot of potential for hormonal dysregulation. I haven’t noticed any negative symptoms yet though.” – female reader submission
  • “It helped regulate my hormones (DHEA) and recompositioned my body to have less fat and more muscle. I started doing 16/8 and I now do ~20/4” – female reader submission
  • “I do the 16/8 method and I feel like it helps me stay where I want to be, and I notice that if I do ever get sick, it seems to go away quickly, and it really makes a difference inflammation-wise in my body. I can totally feel the difference during my period. But if there’s a day I’m hungry in the morning, I eat. I’m not strict about it.” – female reader submission
  • “I was on and off it for a few months, then committed in the new year and it’s honestly changed my life. I feel a million times better, the inches are falling off (still waiting on the weight, but I’ve dropped some clothes sizes), inflammation is gone. In a month, I’ve been told it looks like I’ve dropped 30 pounds, but it’s been 10. All by clean eating and fasting 16 hours.” – female reader submission 
  • “I did If for about a month and it actually triggered horrible migraines and anxiety for me. I never had experienced migraines or anxiety prior to IF and there were no other factors that my neurologist could link these to other than IF. I was eating between 12-8 pm and think cutting out that usual breakfast time may have meant I wasn’t eating as much as usual.” – female reader submission
  • “I did IF for over a year and I loved how it made m feel. The only reason I stopped was because. Got a new job and my work hours changed. I would do a 16-18  hour fast everyday and would eat from between 12 or 2 to 8pm. It didn’t make me have any restrictive eating habits / thought but I can definitely see that happening to some. I mostly kept up with it because it helped my digestive issues a ton. And helped me from snacking obsessively at night which I sued to do every night and even now over a year after I stopped IF I don’t feel the need / want to snack at night almost ever. The biggest critique I have is that it’s not really sustainable for people who have t one going for a long time every da. I ended up stopping because I work 10-7 but I wake up to workout most days between 5:30-6 so I’m almost never home during my old eating  window and it’s impossible from to not eat while/right after I cook something.” – female reader submissions
  • “I have done IF where I fast 16 hours and eat 8 hours window for the last 1.5 years, It has completely eliminated may bloating (which used to occur very regularly(, has reduced my sugar cravings, and has ended my feelings of constantly being in a state of hunger. I’ve also noticed I get sick less frequently and bounce back from sicknesses much more quickly.” – female reader submissions
  • “During Ramadan, I usually have a very delayed period when I’m fasting. So instead of 30 days, it extends to 40 or 45 days. I have a very temperamental cycle though, that’s easily affected by change or increased stress. A few of my friends have unaffected cycles during this time, and a few like me have irregularities. It is only for the month where I’m fasting and then it returns to normal. Oddly enough I like to keep a 12-13 hour window between dinner and breakfast almost daily and that has no effect. It’s just when it’s over 13 hours.” – female reader submission ***during Ramadan, fasting occurs from dawn until sunset, which is against the theory of eating with natural circadian rhythms 

Long-term implications?

  • Whether the effect of the 1 meal/d diet on glucose tolerance would persist, exacerbate or resolve over time beyond the 2 month experimental diet period of our study is an important question relevant to long-term effects of the diet. However, we did find that the effect of the 1 meal/d diet on glucose tolerance was rapidly reversed upon return to the 3 meal/d diet, indicating that the diet had no long-lasting effect on glucose metabolism (normal weight adults consuming 1 meal per day in 4 hour time period or 3 meals per day throughout the day for 8 weeks) ( 10 )

To recap:

  • Decrease in body weight and improved sleep in young, healthy men with 11 hours nightly restriction. No change in total mood in men fasting 11 hours.
  • Decrease in fat mass with maintenance of fat-free mass in young men who fasted 16 hours per day, Testosterone and insulin-like growth factor 1 decreased significantly in TRF, with no changes in normal diet. Adiponectin increased in time restricted fasting while total leptin decreased, although not when adjusted for fat mass. Triiodothyronine decreased in time restricted fasting, but no significant changes were detected in thyroid-stimulating hormone. No difference in muscle changes between the group that didn’t time restrict feeding. No significant changes were detected in thyroid-stimulating hormone, total cholesterol, high-density lipoprotein, low-density lipoprotein, or triglycerides.
  • Higher morning fasting plasma glucose when one meal consumed between 4-8pm compared to 3 meals per day, though no significant changes to fasting insulin, insulin sensitivity, or hunger hormones (Ghrelin, Adiponectin, resisting, BDNF). There was also a reduction in fat mass, increases in LDL and HDL
  • in healthy lean women, omitting breakfast led to higher plasma total and LDL cholesterol concentrations and lower insulin sensitivity and that eating breakfast led to total lower energy intake than the group who omitted breakfast, though no changes in body weight. This study, however, allowed participants to eat up until 9pm. There was no hard cut off for limiting feed period in the evenings.
  • During fasting holidays like Ramadan in healthy adults, decrease in inflammatory markers (IL-6, CRP and homocysteine)
  • May have negative effects on glucose tolerance by eating 1 large meal a day close to bedtime (consumed between 5-9pm for 8 weeks). This effect, however, didn’t last when participants returned to a 3 meal per day diet. It may have also been caused by eating late at night.
  • Some women feel subjectively amazing, have experienced restoration of hormone imbalances, get over being sick in a shorter amount of time, while others find it difficult to fit into their schedules, and have even experienced migraines.

TRF in COMBINED OVERWEIGHT AND NON-OVERWEIGHT SUBJECTS

***many studies are not specifically time restricted feeding, but instead are studies “skipping breakfast.” These studies are inherently biased, as they don’t offer a firm cut-off point for eating at night.

Physical:

  • overweight participants consumed greater amounts of energy than normal weight participants in the early evening, and breakfast omitters consumed more late at night compared to breakfast eaters. Participants in this study were not restricted to eating during certain hours per day and food was consumed up until midnight. This study, however, did not put a limit on timing of eating in the evening. It only looked at skipping breakfast, rather than a true time restricted feeding schedule. Participants in this study were not restricted to eating during certain hours per day and food was consumed up until midnight. (skipping breakfast in normal weight vs overweight adults for 2 weeks) ( 15 )
  • removing breakfast also affected the timing of subsequent energy intakes with more energy being consumed during the afternoon. Regardless of BMI and usual breakfast habit, significantly less energy, carbohydrate and fiber were consumed in no breakfast conditions.  This study, however, did not put a limit on timing of eating in the evening. It only looked at skipping breakfast, rather than a true time restricted feeding schedule. Participants in this study were not restricted to eating during certain hours per day and food was consumed up until midnight. (skipping breakfast in normal weight vs overweight adults for 2 weeks) ( 15 )
  • Breakfast omitters consumed more than breakfast eaters later in the evening. All groups consumed significantly less energy, carbohydrate and fiber in the no breakfast condition however overweight participants increased their sugar intakes. This study, however, did not put a limit on timing of eating in the evening. It only looked at skipping breakfast, rather than a true time restricted feeding schedule. Participants in this study were not restricted to eating during certain hours per day and food was consumed up until midnight.  (skipping breakfast in normal weight vs overweight adults for 2 weeks) ( 15 )
  • intervention group reduced the estimated daily caloric intake (average reduction 20%) (reducing eating interval to 10-11 hours in healthy overweight adults for 3 weeks) ( 21 )
  • reducing the temporal eating period in a feasibility study imparted measurable benefits of clinically relevant magnitude in terms of body weight reduction and sleep improvement without increasing the subjective sense of hunger (reducing eating interval to 10-11 hours in healthy overweight adults for 3 weeks) ( 21 )
  • relatively large effect on body weight reduction, even in the small intervention cohort, implies that the benefits might result from multiple changes: restoration of the diurnal rhythm of feeding/fasting, reduction of the weekday/weekend metabolic jetlag, and a reduction in the daily caloric intake (reducing eating interval to 10-11 hours in healthy overweight adults for 3 weeks)( 21 )

Emotional:

  • in a subjectiveself-assessment of sleep satisfaction, hunger at bedtime, and energy level (in the mornings, and overall over the past few days), statistically significant improvement was observed. All participants voluntarily expressed an interest in continuing unsupervised with the 10–11 hr time-restricted eating regimen after the conclusion of the 16-week supervised intervention. After 36 weeks (1 year since the intervention began), the participants maintained weight loss and sleep improvement and felt more energetic (reducing eating interval to 10-11 hours in healthy overweight adults for 3 weeks) ( 21 )

To recap:

  • overweight participants consumed greater amounts of energy than normal weight participants in the early evening, and breakfast omitters consumed more late at night compared to breakfast eaters. This study, however, did not put a limit on timing of eating in the evening. It only looked at skipping breakfast, rather than a true time restricted feeding schedule. Participants in this study were not restricted to eating during certain hours per day and food was consumed up until midnight.  (skipping breakfast in normal weight vs overweight adults for 2 weeks) ( 15 )
  • Breakfast omitters consumed more than breakfast eaters later in the evening. This study, however, did not put a limit on timing of eating in the evening. It only looked at skipping breakfast, rather than a true time restricted feeding schedule. Participants in this study were not restricted to eating during certain hours per day and food was consumed up until midnight.( 15 )
  • Regardless of BMI and usual breakfast habit, significantly less energy, carbohydrate and fiber were consumed in no breakfast conditions. This study, however, did not put a limit on timing of eating in the evening. It only looked at skipping breakfast, rather than a true time restricted feeding schedule. Participants in this study were not restricted to eating during certain hours per day and food was consumed up until midnight. ( 15 )
  • adults who reduced eating interval to 10-11 hours, reported benefits in terms of body weight reduction and sleep improvement without increasing the subjective sense of hunger ( 21 )

 

Reasons for Intermittent Fasting

(beyond weight loss / cardio-metabolic factors)

Improved gut health:

  • Fasting regimens appear to have positive impacts on the gut microbiota by enhancing gut epithelial integrity, though the type of fasting wasn’t mentioned in the study ( 12 )
  • TIMING OF EATING AND CONSISTENCY IS WHAT’S KEY – Chronic circadian misalignment in mice and time-shift-induced jet lag in humans result in dysbiosis and transmissible metabolic consequences, including obesity and glucose intolerance ( 20 )

The metabolic shift/clock:

  • Circadian rhythms are daily ∼24 hr rhythms in metabolism, physiology, and behavior that are sustained under constant light or dark conditions. ( 16 )
  • Circadian clock intimately interacts with nutrient-sensing pathways. Frequent eating and the absence of a defined fasting period likely sustain modestly elevated levels of fed-state physiology and disturb the normal counter-regulatory metabolic state that occurs during fasting ( 16 )
  • Diets that markedly reduce caloric intake on 1 day or more each week (e.g., a reduction to 500 to 700 calories per day) result in elevated levels of ketone bodies on those days (all 3 studies performed in overweight / obese adults) ( 26 )
  • influencing these major cellular pathways, ketone bodies produced during fasting have profound effects on systemic metabolism. Moreover, ketone bodies stimulate expression of the gene for brain-derived neurotrophic factor, with implications for brain health and psychiatric and neurodegenerative disorders ( 26 )
  • the metabolic switch as the body’s preferential shift from utilization of glucose from glycogenolysis to fatty acids and fatty acid-derived ketones. The reason we use the word ‘‘preferential’’ is because there is now a growing body of research to indicate that ketones are the preferred fuel for both the brain and body during periods of fasting and extended exercise ( 27 )
  • a shift from lipid synthesis and fat storage to mobilization of fat in the form of free fatty acids (FFAs) and fatty acid-derived ketones. For this reason, many experts have suggested that IF regimens may have potential in the treatment of obesity and related metabolic conditions, including metabolic syndrome and type 2 diabetes ( 27 )
  • metabolic switch usually occurs between 12 and 36 hours after cessation of food consumption, depending on the liver glycogen con- tent at the beginning of the fast, and on the amount of the individual’s energy expenditure/exercise during the fast ( 27 )
  • when the metabolic switch is flipped, the primary energy source for the body shifts from glucose to FFA derived from adipose tissue lipolysis and ketones, which serve to preserve muscle. In support of this, retention of lean mass is increased following IF regimens for weight loss, as compared with continuous CR regimens in humans ( 27 )
  • Animal models show that intermittent fasting improves health throughout the life span, whereas clinical studies have mainly involved relatively short-term interventions, over a period of months. ( 26 )
  • IF eating patterns may result in a wide range of beneficial effects on health, including improved glucose metabolism, reduced inflammation reduced blood pressure, improved cardiovascular health and increased resistance of cells to stress and disease in humans ( 27 )
  • While humans in modern societies have the opportunity to consume food throughout the day and night (ad libitum), our ancestors typically had to compete amongst themselves and with other species for a limited supply of food. Energy intake was relatively low and intermittent, and energy expenditure relatively high.
  • clinical studies have focused mainly on overweight young and middle-age adults, and we cannot generalize to other age groups the benefits and safety of intermittent fasting that have been observed in these studies ( 26 )

**regarding autophagy

which is essentially the body’s way of cleaning out damaged cells, in order to regenerate newer, healthier cells. I didn’t find any studies done in humans, though there are significant findings in animal studies (here, here)

  • Cells respond to intermittent fasting by engaging in a coordinated adaptive stress response that leads to increased expression of antioxidant defenses, DNA repair, protein quality control, mitochondrial biogenesis and autophagy, and down-regulation of inflammation ( 26 )

**regarding hormone imbalance

 studies also done on rats

  • The one single study that is repeatedly reference by various healthcare professionals is performed on rats. It is a fasting regimen that negatively influences reproduction in young animals due to its adverse effects on complete hypothalamus-hypophysial-gonadal axis. In the study, female rats engaged in intermittent fasting for 12 weeks, and at the end of just two weeks, they had smaller ovaries and experienced more insomnia than male mice. After two weeks of intermittent fasting, female rats stopped having menstrual cyclesand their ovaries shrunk while experiencing more insomnia than their male counterparts (though the male rats did experience lower testosterone production). This study, however, was alternate day fasting NOT time restricted fasting. Because of the type of fasting, and the fact that it was a study performed on rats, it’s impossible to deduce a similar result for humans.
  • Here’s why this matters. this study reported that IF-DR regimen resulted in altered pattern of serum leptin level in both male and female rats. The results indicate that IF-DR significantly decrease serum leptin level in female rats as compared to control group, and leptin is thought to play a role in LH secretion (an important hormone for fertility and menstruation patterns) ( 35 ). In overweight women and obese adults, leptin was unchanged after fasting conditions (daily caloric restriction vs 70% restriction on 2 consecutive days in overweight women – 2 ) (daily breakfast consumption vs extended morning fasting in obese adults for 6 weeks 11 ). Ironically, leptin decreased in a study of men, but not when adjusted for fat mass (16/8 hour time restricted fasting in young, healthy men for 8 weeks – 29 ). So you can see why these results don’t 100% translate to humans.
  • FURTHERMORE!!!! The rats in the study were fed at 10am and rats are by nature nocturnal creatures. Many postulations regarding the benefits of intermittent fasting are eating with our natural circadian rhythms. If rats are accustomed to eating during the night and are suddenly provided a large portion of food during the day, this could disrupt the natural metabolic cycle, in turn leading “metabolic jet-lag” and a stress response, which results in a cascade of hormonal changes, insulin included – aka THIS COULD BE A CONFOUNDING VARIABLE. Not only for this study, but perhaps many studies that look at intermittent fasting in mice/rats. ( 35 ). For example, in one human study listed above, the one participant whose insulin levels worsened on evening time restricted fasting had reported a long history of overnight shift work prior to enrolling in the trial. Given that circadian rhythms are altered in adults who perform overnight shift work, it will be important to determine whether some subpopulations have altered circadian rhythms and would benefit more from alternative meal timing interventions (restricting feeding from 7am-3pm in pre-diabetic males for 5 weeks) ( 34 ).

Given the above findings (the one study), various professionals recommend something called “crescendo fasting” for women. This means, pick 2-3 non-consecutive days to fast between 12-16 hours. It’s recommended to avoid intense workouts on fasting days, and to avoid fasting during menses. Eat normally on non-fasting days and drink plenty of water. If you give this slow and steady approach to intermittent fasting a try for a couple weeks/months and feel great, you may consider going for a longer window, always gauging how you feel. (37 )

Overall conclusions:

  • HIGHLY DEPENDENT ON REASONS YOU’RE FASTING, WHAT KIND OF FASTING, AND YOUR STARTING POINT. When looking at the research, I think it’s vitally important to note who was studied, what kind of fasting was performed, and for how long.
  • Consistency is key in terms of the metabolic clock and shift. Eating at the same times every day, with or without time restricted feeding seems to be most supported in the literature. 
  • I think we evolved with more time fasting than we currently have in the standard American diet, especially with food and snacks so readily available and consumable. I overall believe there is value for most in a 12 hour fast, between your last meal of the day and the following morning. This seems to be the safest form with fewest averse side effects. Though if at any time, this begins to lead to disordered thoughts or behavior around food, then it most certainly would require reconsideration.
  • Point blank, we need more research. Specifically on time restricted fasting in women. I navigated towards studies in women that omitted breakfast, though this is certainly not a true 1:1 comparison. Especially since in those studies, there was no cut off point for eating in the evening, which I noted above.
  • Overall, evidence suggests that intermittent fasting regimens are not harmful physically or mentally (i.e., in terms of mood) in healthy, normal weight, overweight, or obese adults ( 16 ). Studies of cognition and mood during extended fasts suggest few or no adverse effects, and improvements in performance in some cognitive domains, including executive function, have been reported. ( 27 )
  • Alternate-day fasting appeared to result in weight loss, as well as reductions in glucose and insulin concentrations in overweight populations. However, this fasting regimen may not be practical because it leads to intense hunger on fasting days. Modified alternate day fasting or time restricted fasting may be a better, less intense / severe option. Modified alternate-day fasting regimens result in reduced weight, with reductions ranging from 3.2%, in comparison with a control group ( 16 )
  • Per a systematic review from NEJM, “Physicians can advise patients to gradually, over a period of several months, reduce the time window during which they consume food each day, with the goal of fasting for 16 to 18 hours a day. Alternatively, physicians can recommend the 5:2 intermittent-fasting diet, with 900 to 1000 calories consumed 1 day per week for the first month and then 2 days per week for the second month, followed by further reductions to 750 calories 2 days per week for the third month and, ultimately, 500 calories 2 days per week for the fourth month. A dietitian or nutritionist should be consulted to ensure that the nutritional needs of the patient are being met and to provide continued counseling and education. As with all lifestyle interventions, it is important that physicians provide adequate information, ongoing communication and support, and regular positive reinforcement.” ( 26 )

CONTRAINDICATIONS OF INTERMITTENT FASTING

  • Children and teenagers still growing
  • Women who are pregnant / breast-feeding
  • Recovering from surgery
  • History of eating disorder / disordered eating patterns
  • Taking certain medications (especially those that need to be absorbed with food)
  • Diabetics on insulin
  • With hormone imbalance, if a woman is trying to maximize fertility, unless that woman is really overweight and has blood sugar issues, in which case intermittent fasting may actually move the needle in the positive direction ( 35 )
  • If someone has pretty significant HPA axis dysregulation or adrenal fatigue — so that would manifest as feeling tired when you wake up in the morning even if you get enough sleep, having afternoon energy crashes, not being able to fall asleep or stay asleep, your quality of sleep is poor, you have poor stress tolerance, poor exercise recovery or exercise tolerance ( 36 )
  • If you experience symptoms of hormonal imbalance: your period becomes irregular, you start having problems sleeping or falling asleep, you notice changes in metabolism and digestion, you feel moody or experience brain fog, you notice negative changes in how your hair and skin looks, you’re always cold (37 )

Tips to remember about research studies:

Even if a review summary of evidence based studies makes certain claims, it’s important not to take them at face value. A healthline article which uses evidence based articles to support its claims, for example, states that there’s increase in human growth hormone which may facilitate fat burning and muscle gain. This study, however, was done exclusively in very small subsets of men.  It also reports an improvement in cellular repair and gene expression, though this study was done exclusively in mice / animals. Not to at all imply that this research isn’t valid, but it also doesn’t translate to the general population. It takes diving a little deeper and knowing what to look for. Aka be wary of what you read on the internet, and what is deduced from research studies. They are often done on very specific populations of people and imply CORRELATION, not causation.

For a full outline of all the studies I researched, click –> intermittent fasting in humans notes – Katie Lemons (2020)

For more tips on how to dissect a research study, click here.

An overview of the lab values:

GHRELIN

what is it: hunger hormone – stimulates appetite, increases food intake, promotes fat storage

  • women had significantly lower glucose, insulin, free fatty acid, triacylglycerol, and LDL-cholesterol concentrations and significantly higher HDL-cholesterol and ghrelin concentrations than did the men(zero calorie alternate day fasting in non-obese men and women for 3 weeks) ( 7 ) (zero calorie alternate day fasting in non-obese men and women for 3 weeks) (  7 )
  • Fasting glucose, ghrelin (hunger hormone), resting metabolic rate, systolic, and diastolic blood pressure, were not significantly changed from baseline in the men or the women (zero calorie alternate day fasting in non-obese men and women for 3 weeks) (  7)
  • range of hormones implicated in the regulation of appetite and energy balance also did not differin response between treatments (leptin, total ghrelin, acylated ghrelin, peptide YY, active glucagon-like peptide-1, and adiponectin)  (daily breakfast consumption vs extended morning fasting in obese adults for 6 weeks) ( 11 )
  • there were no significant effects of meal frequency on plasma levels of ghrelin, adiponectin, resistin or BDNF(normal weight adults consuming 1 meal per day in 4 hour time period or 3 meals per day throughout the day for 8 weeks) ( 10 )
  • evening time restricted fast did not affect morning fasting levels of the hunger hormone ghrelin (restricting feeding from 7am-3pm in pre-diabetic males for 5 weeks) ( 34 )

LEPTIN

what is it: satiation hormone – inhibits hunger, which in turn diminishes fat storage in adipocytes

In overweight women and obese adults, leptin was unchanged in both 5:2 intermittent fasting and time restricted fasting (as definited by breakfast omission), in overweight adults. (daily caloric restriction vs 70% restriction on 2 consecutive days in overweight women – 2 ) (daily breakfast consumption vs extended morning fasting in obese adults for 6 weeks 11 ). Leptin was decreased in a study of men who were doing 16/8 fasting, but not when adjusted for fat mass (16/8 hour time restricted fasting in young, healthy men for 8 weeks – 29 ).

BDNF

What is it: plays an important role in neuronal survival and growth, serves as a neurotransmitter modulator, and participates in neuronal plasticity, which is essential for learning and memory ( here )

  • there were no significant effects of meal frequency on plasma levels of ghrelin, adiponectin, resistin or BDNF (normal weight adults consuming 1 meal per day in 4 hour time period or 3 meals per day throughout the day for 8 weeks) ( 10 )
  • alternate day fasting induces long-term changes in BDNF secretion, which may contribute to improved weight loss maintenance through effects on energy balance (8 weeks zero calorie alternate day fasting in obese adults) ( 4 )

TSH / THYROID HORMONES

  • Thyroid hormones that regulate resting metabolic rate were unresponsive to either treatment, with systemic concentrations of triiodothyronine (free-T3) and thyroxine (free-T4) closely matched between treatments at baseline and follow-up(daily breakfast consumption vs extended morning fasting in obese adults for 6 weeks) ( 11 )
  • Triiodothyronine decreased in time restricted fasting, but no significant changes were detected in thyroid-stimulating hormone, total cholesterol, high-density lipoprotein, low-density lipoprotein, or triglycerides.Resting energy expenditure was unchanged, but a significant decrease in respiratory ratio was observed in the time restricted fasting group (16/8 hour time restricted fasting in young, healthy men for 8 weeks) ( 29 )

RMR (resting metabolic rate)

  • Resting metabolic rate (RMR) decreased significantly in caloric restriction but not in alternate day fasting over the 8-week intervention (8 weeks zero calorie alternate day fasting in obese adults) ( 4 )
  • Fasting glucose, ghrelin (hunger hormone), resting metabolic rate, systolic, and diastolic blood pressure, were not significantly changed from baseline in the men or the womenFasting insulin was lower on day 22 in both the men and the women (zero calorie alternate day fasting in non-obese men and women for 3 weeks) (  7 )
  • resting metabolic rate was stable from baseline to follow-up, with no difference between groups in response to the intervention (daily breakfast consumption vs extended morning fasting in obese adults for 6 weeks) ( 11 )

INSULIN

  • Both groups experienced modest declines in fasting serum insulin and improvements in insulin sensitivity which were greater amongst the intermittent energy restriction group (25% caloric restriction all days vs 75% restriction on 2 consecutive days in obese young women for 6 months) ( 6 )
  • Intermittent energy and carbohydrate restriction diet is superior to the daily energy restriction diet with respect to the improvements in insulin sensitivity and the loss of body fat (daily caloric restriction vs 70% restriction on 2 consecutive days in overweight women) ( 2 )
  • Labs: Reductions in insulin resistance, weight, adiposity, circumferences, leptin, IL-6 and lipids were maintained during the final weight maintenance month in all groups (intermittent fasting, intermittent fasting + ad libitum fat/protein consumption, and caloric restriction) (daily caloric restriction vs 70% restriction on 2 consecutive days in overweight women) ( 2 )
  • women had significantly lower glucose, insulin, free fatty acid, triacylglycerol, and LDL-cholesterol concentrations and significantly higher HDL-cholesterol and ghrelin concentrations than did the men (zero calorie alternate day fasting in non-obese men and women for 3 weeks) ( 7 )
  • Fasting glucose, ghrelin (hunger hormone), resting metabolic rate, systolic, and diastolic blood pressure, were not significantly changed from baseline in the men or the womenFasting insulin was lower on day 22 in both the men and the women (zero calorie alternate day fasting in non-obese men and women for 3 weeks) (  7 )
  • decreased insulinemic response to an OGTT in those consuming breakfast relative to an increase in those extending their fast; and 4) no evidence that the omission of breakfast had any effect on body weight. (daily breakfast consumption vs extended morning fasting in obese adults for 6 weeks)( 11)
  • Although 5 weeks of evening time restricted fast did not improve glucose levels, it dramatically lowered insulin levels and improved insulin sensitivity and β cell responsiveness. (restricting feeding from 7am-3pm in pre-diabetic males for 5 weeks) ( 34 )

References

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( 7 ) Heilbronn, L.K., Smith, S.R., Martin, C.K., Anton, S.D., & Ravussin, E. (2005). Alternate-day fasting in nonobese subjects: effects on body weight, body composition, and energy metabolism. The American Journal of Clinical Nutrition, 81(1), 69-73. https://doi.org/10.1093/ajcn/81.1.69

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( 13 ) Farshchi, H.R., Taylor, M.A., & Macdonald, I.A. (2005). Deleterious effects of omitting breakfast on insulin sensitivity and fasting lipid profiles in healthy lean women. The American Journal of Clinical Nutrition, 81(2), 388-396. https://doi.org/10.1093/ajcn.81.2.388

( 14 ) Schlundt, D.G., Hill, J.O., Sbrocco, T., Pope-Cordle, J., & Sharp, T. (1992). The role of breakfast in the treatment of obesity: A randomized clinical trial. The American Journal of Clnical Nutrition, 55(3), 645-651. https://doi.org/10.1093/ajcn/55.3.645

( 15 ) Reeves, S., Huber, J.W., Halsey, L.G., Horabady-Farahani, Y., Ijadi, M., & Smith, T. (2014). Experimental manipulation of breakfast in normal and overweight/obese participants is associated with changes to nutrient and energy intake consumption patterns. Physiology & Behavior, 22(133), 130-135. doi: 10.1016/j.physbeh.2014.05.015

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4 Responses

  1. WOW, just WOW. As a nurse practitioner and former clinical research coordinator I am in awe by how well you were able to dive into all this literature and so comprehensively summarize the vast array of research AND use human studies! This must have taken SOOO much time but it is so worthwhile for those considering intermittent fasting to read.

    This is the heart of medicine. Making EVIDENCE BASED recommendations and informed decisions!

    I have become increasingly bothered by the claims of influencers, medical professionals or “health coaches” in the realm of social media which often have no evidence backing their claims or use skewed data that no one thinks to actually look up and confirm the findings.

    Well done!

    1. KRISTIN!! I can’t even tell you how much this comment means to me. IT TOOK SO MUCH TIME! But was hopefully well worth it. I wanted something where people could understand that with these studies, context is everything. So human was the way to go. I too feel that frustration and am trying to lead by example that we can’t just copy paste a study to prove a point without very clearly highlighting its context – who was study, type of study, limitation of the study, etc. Thank you again for the acknowledgement! Seriously means the world and makes it all worth it.

  2. This blog is amazing. I’m a new PA-C as well and wish I’d seen something like this in school. Thank you!!

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