Potential Benefits and Harms of Intermittent Energy Restriction and Intermittent Fasting Amongst Obese, Overweight and Normal Weight Subjects—A Narrative Review of Human and Animal Evidence
Abstract
:1. Introduction
2. Methods
3. Results
3.1. Is IER Associated with Greater Weight Control than CER?
3.1.1. Weight Loss amongst People with Overweight or Obesity
3.1.2. Adherence to IER and CER amongst People with Overweight or Obesity
3.1.3. Maintaining Weight Loss amongst People with Overweight or Obesity
3.2. Prevention of Weight Gain amongst Normal Weight Subjects
4. Metabolic Effects of IER vs. CER
4.1. Adipose Stores and Adipocyte Size
4.1.1. Human Studies
4.1.2. Animal Studies
4.2. Fat Free Mass
Human Studies
4.3. Resting Energy Expenditure
Human Studies
4.4. Peripheral and Hepatic Insulin Resistance
4.4.1. Human Studies
4.4.2. Animal Studies
5. Metabolic Flexibility
5.1. Is IER Safe?
5.2. Is There an Optimal IER Regimen?
6. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
Abbreviations
ER | energy restriction |
CER | continuous energy restriction |
IER | Intermittent energy restriction |
ADER | alternate day energy restriction |
IF | Intermittent fasting |
FFA | free fatty acids |
FFM | fat free mass |
REE | resting energy expenditure |
MUFA | monounsaturated fatty acid |
HOMA | homeostatic model assessment |
Appendix A
# | Searches | Results |
---|---|---|
1 | ((intermittent or “alternate day” or modified) adj1 (fasting or diet or “energy restriction” or “calor* restriction”)).mp. [mp=title, abstract, original title, name of substance word, subject heading word, keyword heading word, protocol supplementary concept word, rare disease, supplementary concept word, unique identifier] | 854 |
2 | (body adj1 (fat or weight)).mp. [mp=title, abstract, original title, name of substance word, subject heading word, keyword heading word, protocol supplementary concept word, rare disease supplementary concept word, unique identifier] | 308923 |
3 | (fat adj1 (liver or hepatic)).mp. [mp=title, abstract, original title, name of substance word, subject heading word, keyword heading word, protocol supplementary concept word, rare disease supplementary concept word, unique identifier] | 2661 |
4 | "ectopic fat".mp. | 445 |
5 | (“fat free mass” or “muscle mass”).mp. [mp=title, abstract, original title, name of substance word, subject heading word, keyword heading word, protocol supplementary concept word, rare disease supplementary concept word, unique identifier] | 15776 |
6 | “resting energy expenditure”.mp. | 2708 |
7 | Insulin/ or insulin.mp. | 340396 |
8 | “metabolic flexibility”.mp. | 371 |
9 | body weight/ or exp body weight changes/ or exp overweight/ | 365308 |
10 | exp Adipose Tissue/ | 82804 |
11 | Insulin/ or Insulin Resistance/ | 199942 |
12 | exp Calorimetry, Indirect/ or exp Basal Metabolism/ or exp Energy Metabolism/ or exp Energy Intake/ | 361348 |
13 | 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12 | 1115315 |
14 | 1 and 13 | 424 |
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Reference | IER Regimens | Study Population | Study Design | Primary End Point and Power of the Study | |||
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N, Gender, Age | Baseline BMI (kg/m2) Mean (SD) Range | Diet Groups (N) | Level of Support | Duration of Study | |||
Hill et al. 1989 [26] | 3–7 day periods of alternating 70%, 60%, 45%, and 10% ER. Overall 40% CER | 40 women (32 completers) | 31 (3.0) | IER = 10 IER + exercise = 10 40% CER = 10 40% CER + exercise = 10 | 12 weekly group meetings. Menus provided. | 12 weeks intervention and follow up 6 months after the weight loss programme | Weight loss No power calculation |
Ash et al. 2003 [27] | 4 consecutive days/week 50% ER (4.18 MJ liquid very low calorie diet 3 days/week, ad lib healthy eating) Overall 30% CER | 51 men with Type 2 diabetes Age < 70 years | 31.2 (3.4) 25–39.9 | IER vs. 2 types of 30% CER IER = 14 30% CER = 20 (self-selected meals) 30% CER = 17 (pre-portioned meals) | Face to face visit the clinic dietitian and physician fortnightly and telephone contact with the dietitian on intervening weeks. | 12 weeks | Weight loss and glycaemic control No power calculation |
Varady et al. 2011 [14] | Alternate days of 75% ER (1.67–2.50 MJ/day) and AL low fat/American Heart Association diet: 30% kcal fat, 15% kcal protein, 55% kcal carbohydrate. Overall 25% CER | 51 women and 9 men Age 35–65 years | 32 (2.0) 25–39.9 | IER = 15 (pre-portioned meals on fast days) 25% CER = 15 (pre-portioned meals) Exercise only =15 (180 minutes 70% max heart rate) Control = 15 | No information | 12 weeks | LDL and HDL particle size No power calculation |
Harvie et al. 2011 [12] | 2 consecutive days/week 70% ER (2.73 MJ/day, 50 g protein: 2 pints of milk, 1 portion of fruit and 4 portions of vegetables) 5 days ad libitum healthy eating. Overall 25% CER | 107 premenopausal women Age 30–45 years | 30.6 (5.1) 24–40 | IER = 53 25% CER = 54 | Fortnightly motivational phone calls and monthly clinical appointments with dietitian. Advised to maintain current levels of physical activity. | 26 weeks | Insulin resistance 80% power to detect a 25% difference |
Harvie et al. 2013 [13] | IECR: 2 consecutive days/week 70% ER (energy and carbohydrate restriction: 2.73 MJ/day, 70 g protein, 50 g carbohydrate) Overall 25% CER 2 days 60% ER. or IECR + PF: 2 consecutive days/week 50% ER (energy and carbohydrate restriction: ~4.18 MJ/day, 80 g protein, 50 g carbohydrate) | 115 women aged 20–69 years | 31 (5.0) 24–45 | IECR = 37 IECR + PF = 38 25% CER = 40 2 days/week IECR vs. IECR + PF 1 days/week vs. isoenergetic CER diet | Fortnightly motivational phone calls and monthly clinical appointments with dietitian. Advised to achieve 5 × 45 min of moderate intensity physical activity per week—but achieved minimal changes in the three groups | 13 weeks weight loss phase. 4 weeks weight maintenance phase. | Insulin resistance 80% power to detect a 20% difference |
Carter et al. 2016 [33] | IECR 2 days per week 1.67–2.5 MJ/day (70%–85% restriction) and habitual eating for 5 days | 63 30 men 33 women Type 2 diabetes Age > 18 Mean (SD) age 61 (7.5) | 35 (4.8) | IECR = 31 + exercise (2000 steps) CER = 32 5.0–6.5 MJ (35%–45%) + exercise (2000 steps) | Asked to record dietary intake throughout the 12-week study. Fortnightly appointments with dietitian | 12 weeks | HbA1c No power calculation |
Outcomes | ||||||
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Reference | Dropout % of Subjects | Dietary Adherence Methodology | Final Analysis | Weight change Mean (SD) % Weight Loss | Change in Body Fat and fat Free Mass (FFM) Method of Assessment | Metabolic Effects |
Hill et al. 1989 [26] | 12 weeks/6 months after intervention IER = 40%/60% IER + exercise = 0%/0% 40% CER = 20%/70% 40% CER + exercise = 20%/40% Combined IER + IER + exercise = 20%/30% Combined CER + CER + exercise = 20%/55% | 12 week diet records Average daily intake IER = 4.97 (0.59) MJ IER + exercise = 4.58 (2.92) MJ 40% CER = 5.46 (1.49) MJ 40% CER + exercise = 4.59 (0.30) MJ p > 0.05 | Completers analysis | 12 week data Combined IER/CER diet only groups Weight −6.5 (0.9) kg (−7.6%) Combined IER/CER + exercise −8.6 (0.9) kg (−8.8%) | Body density from underwater weighing IER = CER Fat loss (kg): IER 6.0 (0.8) CER 6.1 (0.6) p > 0.05 Loss of FFM: Combined all groups 47.6 (1.1) to 46.0 (1.0) p < 0.05 | Equal reductions in blood pressure and triglycerides with IER vs. CER. No change in insulin with IER or CER (p > 0.05) Reduced total cholesterol IER −14% vs. CER −6% (p < 0.05) |
Ash et al. 2003 [27] | IER = 0% 30% CER (self-selected meals) = 0% 30% CER (pre-portioned meals) = 0% | 24 hour recalls All groups mean (SD) reduction in average daily energy intake −2.36 (2.78) MJ ~30% energy restriction | Completers as no drop outs | IER = CER Combined IER/CER group 6.5 (6%) | DEXA IER = CER % Body fat loss: IER −2.0 (1.1)% CER (self-selected meals) −0.9 (1.4)% CER (pre-portioned meals) −2.6 (1.6) % (p = 0.41) FFM: no data | Reduced HbA1c and triglycerides IER = CER p > 0.05 |
Varady et al. 2011 [14] | IER = 13% 25% CER = 20% Exercise = 20% Control = 20% | No data | BOCF | IER −5.2 ± 1.1% CER −5.0 ± 1.4% Exercise −5.1 ± 0.9% Control −0.2 ± 0.4% | No data | Increase in LDL particle size IER = CER p > 0.05 |
Harvie et al. 2011 [12] | IER = 20% 25% CER = 13% 9% of potential recruits did not tolerate the 2 day trial of the restricted days of IER and did not enter the study Drop out due to problems adhering to the diet: IER = 5%, CER = 5%. At the end of the trial, 31 of IER (58%) and 46 of CER (85%) subjects planned to continue the diet allocated at randomization. | IER 7 day food diaries at baseline, 1, 3 and 6 months Potential restricted days completed 0–6 months: mean (95% CI) 66 (55%–77%) Overall average daily reduction in energy intake: mean (95% CI) 12 weeks IER −2.40 (−2.94 to −1.87) MJ (~30% restriction) CER −1.65 (−2.11 to −1.18) (~21% restriction), p = 0.04 26 weeks IER −2.40 (−2.94 to −1.87) (~30% restriction) CER −1.73 (−2.13 to −1.37) MJ (~21% restriction), p = 0.04 | LOCF | IER = CER 12 weeks IER −6.3 (4.5)% CER −5.0 (3.6)% p = 0.11 24 weeks IER −7.8 (5.9%) CER −6.6 (5.0%) p = 0.26 | Bioelectrical impedance IER = CER 12 weeks % Body fat loss: IER −2.4 (2.3)% CER −2.0 (2.1)%, p= 0.42 Body fat mass: IER −3.8 (2.9) kg CER −3.3 (3.0) kg, p = 0.43 24 weeks % Body fat loss: IER −3.4 (3.2%) CER −2.8 (2.7) %, p = 0.35 Body fat mass: IER −5.0 (4.4) kg CER −4.4 (3.9) kg, p = 0.34 21% of weight lost as FFM in IER and CER p = 0.99 | Reduction in HOMA insulin resistance IER > CER at 12 and 24 weeks. Mean difference (95% CI) 12 weeks: −17 (−33.2 to −0.2), p = 0.046. 24 weeks: −23% (−38 to −8.6)%, p = 0.001. Reduced total LDL cholesterol, triglycerides and blood pressure IER = CER p > 0.05 |
Harvie et al. 2013 [13] | IECR = 11% IECR + PF = 26% 25% CER = 33% Drop out due to problems adhering to the diet: IECR 0% IECR + PF 5% CER 5% | 7 day food diaries at baseline, 1, 3 and 4 months Potential restricted days 0–4 months mean (95% CI): IECR 76 (67%–81%) IECR + PF 74 (64%–84%) Overall average daily reduction in intake median, %: 12 weeks IECR = −2.97 MJ, −36% IECR + PF = −2.3 MJ, −29% DER = −2.63 MJ, −33% p = 0.046 16 weeks IECR = −2.38 MJ, 32% IECR + PF = −2.06 MJ, 26% DER = −2.16 MJ, 25% p = 0.765 | LOCF | No difference in % weight loss between groups at 12 weeks IECR −6.2 (4.6) IECR + PF −5.7 (3.9) CER −4.3 (4.6). % weight change during 1 month of weight loss maintenance: IECR −0.49 (1.7) IECR + PF −0.34 (0.9) CER −0.13 (0.88) p = 0.431 % weight lost as FFM median (95%CI): IECR 36.0 (26.4 to 41.3) IECR + PF 20.4 (13.2 to 27.2) DER 29.3 (25 to 38.1) p = 0.048 | Bioelectrical impedance reduction in body fat mass at 12 weeks IER > CER, p = 0.019 Body fat mass: IECR −3.7 (3.7) kg IECR + PF −3.7 (2.2) kg CER −2.0 (3.3) kg No difference during 1 month of weight loss maintenance: Reduction in body fat/kg IECR −0.58 (1.2) IECR + PF −0.31 (0.7) CER + 0.26 (0.90) p = 0.313 | Reduction in HOMA insulin resistance IECR > CER. Mean (95% CI) change at 12 weeks: −0.2 (−0.19 to 0.66) unit; p = 0.02 After 4 weeks of weight loss maintenance: IECR −0.06 (0.51) IECR + PF + 0.03 (0.6) CER −0.25 (0.53) Unit, p = 0.084 Reduced total LDL cholesterol, triglycerides and blood pressure IECR = IECR + PF = CER |
Carter et al. 2016 [33] | IECR 16% CER 22% | No data | ITT | IECR −6.2 (3.6)% CER −5.6 (4.4)% p = 0.6 | DEXA IER 3.8.(2.7)% CER −4.0 (3.2)% p = 0.8 | HbA1C IER −0.6 (1)% CER −0.5 (0.8) |
Outcome | Effects in People Who Are Obese or Overweight | Effects in People Who Are Normal Weights | Effects in Rodent Studies |
---|---|---|---|
Weight loss/prevention of weight gain | IER = CER for weight loss in six studies which were not powered to detect differences in weight. The study finding are suggestive but not conclusive of no difference between IER and CER weight [12,13,14,26,27,33] | No long term data | N/A |
Proportion of body fat stored as visceral and subcutaneous fat | No data | No data | Mixed results: Reduced visceral and increased subcutaneous fat in female C57BL/6J mice [50]. No change in male C57BL/6J mice [51]. Increased visceral and decreased subcutaneous fat in 4 week old male Sprague Dawley rats [53] and LDL-receptor knockout mice [54]. |
Fat cell size | No data | No data | Reduced in male C57BL/6J mice [51] |
Hepatic fat | No data | Modest increase after a single 24 h fast in men not women [46] | Mixed results: Deposition in IER > CER [53,54] IER = CER [87]. |
Intra myocellular triglycerides | No data | Modest increase after a single 48 hour fast in women but not men [45] | No data |
Insulin sensitivity | Mixed results IER > CER (HOMA) [12,13] Reduced HbA1c IER = CER p > 0.05 [27,33] | Mixed results IER > CER [16] IER = CER [17] | Mixed results IER > CER total body and hepatic insulin sensitivity [73]. IER < CER peripheral insulin sensitivity [74] IER > CER hepatic insulin sensitivity [74] |
Fat free mass | IER = CER [12,26] | No data | No data |
Resting energy expenditure | IER = CER [26,28] IER > CER [18] | No comparison data | No data |
Metabolic flexibility | No data | No data | IER > CER [77]. |
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Harvie, M.; Howell, A. Potential Benefits and Harms of Intermittent Energy Restriction and Intermittent Fasting Amongst Obese, Overweight and Normal Weight Subjects—A Narrative Review of Human and Animal Evidence. Behav. Sci. 2017, 7, 4. https://doi.org/10.3390/bs7010004
Harvie M, Howell A. Potential Benefits and Harms of Intermittent Energy Restriction and Intermittent Fasting Amongst Obese, Overweight and Normal Weight Subjects—A Narrative Review of Human and Animal Evidence. Behavioral Sciences. 2017; 7(1):4. https://doi.org/10.3390/bs7010004
Chicago/Turabian StyleHarvie, Michelle, and Anthony Howell. 2017. "Potential Benefits and Harms of Intermittent Energy Restriction and Intermittent Fasting Amongst Obese, Overweight and Normal Weight Subjects—A Narrative Review of Human and Animal Evidence" Behavioral Sciences 7, no. 1: 4. https://doi.org/10.3390/bs7010004