Intermittent Fasting: Myths, Fakes and Truth on This Dietary Regimen Approach
Abstract
:1. Introduction
1.1. Fasting: A Historical and Social View
1.2. A General View of IF Approaches
IF Method | Features | References |
---|---|---|
ADF Alternate day fasting | A day of eating is alternate to a day ad libitum is alternate to a day of fasting (25% of usual food intake, approximately 500 kcal) | [74] |
IF 5:2 | A five days with normal eating and two days of severe fasting (food intake restricted to 500–800 cal) | [64] |
FMD Fasting-mimicking diet | A five-day fasting dietary regimen centered around natural, healthful items and ingredients (healthy fats and fiber-rich carbohydrate) with no refined carbohydrate (25% of usual food intake and less than 10% of protein) | [75,76] |
PF Periodic fasting | Water-only fasting or FMD for at least two days in succession repeated each month (involves a maximum daily energy intake of 250 kcal for about one week–5-day diet affording 750–1100 kcal) | [77] |
TRF Time-restricting feeding | Daily no energy intake (or restricted amount) for 12–20 h, with eating window of 4–12 h (reduction of at least 20% of caloric intake) | [78] |
eTRF Early time-restricting feeding | Modified TRF in which calories restriction occurs in the first 6–8 h of the day (i.e., eating window starts at 08:00 a. m. to at the maximum 02:00 p.m.) | [79] |
lTRF Late time-restricting feeding | Modified TRF in which the eating window starts late in the day, usually from 02:00 p.m. to at the maximum 08:00 p.m.) | [80] |
1.2.1. ADF-Alternate Day Fasting and 5:2 Diet
1.2.2. TRF—Time-Restricting Feeding (eTRF and lTRF)
2. Food Intake Restriction: An In-Depth Outlook
2.1. IF in Neurological and Psychiatric Disorders: Depression, Anxiety, Mental Health, and Neurodegenerative Diseases
2.1.1. IF and Mental Health
2.1.2. IF, Cognitive Function, and Neurodegeneration
2.2. Examples of Clinical Trials Showing ADF-Based Approach as Primary Dietary Intervention
2.2.1. ADF, Weight Loss, and Cardiovascular Health
2.2.2. ADF and Metabolic Health
2.3. Concluding Remarks on IF: Limitations, Undesired Effects, Changes in Blood Profile and Anthropometric Parameters
- This narrative review only considered publications, reports, and clinical trials published in English. It is well known that there are many materials on IF in other languages (i.e., Chinese and Hindi). This represents a possible bias in the analysis.
- All of the reviewed studies have several limitations. First, the small sample sizes, including a maximum of approximately 100 participants, question whether these studies could adequately detect statistically significant differences in primary and secondary outcome measures; secondly, these studies mainly analyzed overweight adults living in one geographical region, namely the USA (it is not surprisingly considering that in the USA, obesity is reaching epidemic proportion), making it difficult to generalize to other age groups, populations, and food cultures to tailor recommendations and personalize the approach, although we also considered studies from other countries and systematic reviews and meta-analyses that considered various populations. Third, the duration of the studies is often limited, and if, on the one hand, it may impede the detection of significant changes in some parameters, on the other hand, data on feasibility and long-term efficacy are lacking. Moreover, blinding study personnel or participants is not always possible because of the nature of the dietary interventions. Lastly, the introduction of accidental bias during the recruitment phase, rather than missing participant outcome data or self-reporting records, may have resulted in misstatements [1,84,172,180].
- The blood lipid profile is usually positively influenced by IF and CR, suggesting that these two interventions have equivalent effects on these lipid parameters. However, levels of HDL-C, by contrast, generally remain unchanged or slightly decrease with IF [159,162,165]. In fact, HDL-C is rarely improved by changing dietary patterns alone, but it is generally augmented as an answer to endurance exercise training [84,160,187,188,189,190]. The modification of blood lipid profile is strictly related to the degree of weight loss achieved, which is usually similar between IF and CR, although ADF results in a greater relative reduction in fat mass and provides relative preservation of fat-free mass [88]. Since WC is an indicator of visceral fat mass, its greater reduction appears consistent with results attained by ADF intervention [172].
- IF may benefit several different populations, including those with obesity and overweight [159,160,162,163,164,165,167,168], insulin resistance, prediabetes, T2DM [169,170,171], MetS [172,173], and type I diabetes [191]. Furthermore, the efficacy of IF in reducing body weight does not appear to vary according to an individual’s sex or menopausal status [166,192]. Although research is still in its infancy, it is possible that IF may decrease androgen markers in both genders, resulting in a valuable tool for treating hyperandrogenism in females with polycystic ovary syndrome (PCOS) by improving menstruation, fertility, and quality of life. However, IF could be a less desirable option among males because low testosterone levels can negatively affect metabolic health, muscle mass synthesis, and libido [193]. IF is not recommended in individuals with hormonal imbalances; pregnant and breastfeeding women or young children, as no study to date has evaluated the safety of these diets in these population groups; adults of advanced age, as the effects of fasting on aging-induced sarcopenia remain unclear and they have a higher risk of dehydration and malnutrition; and individuals with immune deficiencies [4,73,84]. Despite IF being regarded as generally safe, diabetic patients treated with sulfonylureas or insulin should carefully consider whether IF is the most suitable option and should not undertake this procedure without the help of their physician because of the risk of hypoglycemia. Both dose adjustment and medication discontinuation should be carefully evaluated during ADF according to fasting blood glucose levels [73,84]. Medical supervision is required, especially for adolescents with obesity, for whom IF might be effective for weight control when weight loss is clinically indicated. In particular, as adolescence is the life stage with the highest rate of eating disorder development, the choice between IF and CR should be deeply considered. IF is not a suitable intervention for individuals with a history of eating disorders [84].
- Dehydration, nausea, headache, dizziness, syncope, weakness, cold, and irritable feelings; bad breath, low energy, and hunger pangs represent the most common undesirable effects of IF. These conditions are usually mild and do not hinder participants from continuing their fasting. Many side effects are linked to dehydration; therefore, it is advisable to consume at least 1.5 L of water per day; vitamin and/or mineral supplements, together with 50 g of lean protein consumption on the fast day of IF regimens, help to control hunger, prevent excessive lean mass loss, and control feelings of weakness [73,84].
- Adherence to IF regimens could be superior with respect to CR intervention; however, it usually decreases when the duration of intervention reaches 12 weeks or longer [194]. Furthermore, most physicians are not trained to prescribe specific IF interventions, and they can hardly follow their patients through their journey [1,4,73].
- The effect of diet on mood may also influence adherence: some trials showed that IF had a positive effect on mood over CR, with bad temper being reported only in 3% of the participants; however, in a trial with lean participants, an overall worsening of mood was reported [195]. As a consequence, fasting can be challenging, and hence its practicality in the modern lifestyle can sometimes be debatable. Nevertheless, IF interventions could be easily tailored to patients’ needs without hindering their results in terms of metabolic health and weight loss. Interestingly, exercise during ADF appears to attenuate the dropout rate [188,196,197].
3. Cellular Pathways Influence by Food-Intake Restriction
4. Conclusions and Future Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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IF Method | Advantages | Disadvantages |
---|---|---|
ADF Alternate day fasting |
|
|
IF 5:2 |
|
|
FMD Fasting-mimicking diet |
|
|
PF Periodic fasting | ||
TRF Time-restricting feeding |
|
|
eTRF Early time-restricting feeding |
| |
lTRF Late time-restricting feeding |
|
Clinical Trial | Participants | Trials Weeks | Intervention | Body Weight (kg) | WC | Blood Pressure (mmHg) | Plasma Lipids (mg/dL) | Glucoregulatory Factors (mg/dL) | Adherence and Tolerability | Ref. | |
---|---|---|---|---|---|---|---|---|---|---|---|
Overweight and obese | UIC-004-2009 | 16 obese subjects (12 females, 4 males); age 35–65 y, BMI 30–39.9 kg/m2 | 10 | 3 intervention phases:
| −5.8 | NA | SBP −9.5 | TG −38 | FI NA | No drop in adherence during the different phases | [160] |
TC −37 | |||||||||||
FPG NA | |||||||||||
DBP −1.5 | |||||||||||
LDL-C −29 | |||||||||||
HOMA-IR NA | |||||||||||
HDL-C +2 | |||||||||||
Randomized, parallel-arm feeding trial | 74 subjects with BMI 30–39.9 kg/m2; age 25–65 y | 10 | ADF lunch (ADF-L): 25% of baseline energy needs on the fast day (24 h), and ad libitum on each alternating feed day (24 h) | −3.5 | NA | SBP −2 | TG −6 | FI 0 μIU/mL | Adherence to the fast day energy goal was similar for each group. Compliance of ADF meal was high in each intervention group | [162] | |
TC −1 | |||||||||||
FPG −2 | |||||||||||
DBP −1 | LDL-C −2 | ||||||||||
HOMA-IR −0.3 | |||||||||||
HDL-C −2 | |||||||||||
ADF dinner (ADF-D): 25% of baseline energy needs on the fast day (24 h), and ad libitum on each alternating feed day (24 h) | −4.1 | NA | SBP −5 | TG −9 | FI −2 μIU/mL | ||||||
TC −5 | |||||||||||
FPG −1 | |||||||||||
DBP −3 | LDL-C 0 | ||||||||||
HOMA-IR −0.8 | |||||||||||
HDL-C 0 | |||||||||||
ADF-small meals (ADF-SM): 25% of baseline energy needs on the fast day (24 h), and ad libitum on each alternating feed day (24 h) | −4 | NA | SBP −6 | TG −1 | FI −2 μIU/mL | ||||||
TC −1 | |||||||||||
FPG −2 | |||||||||||
DBP −1 | LDL-C +1 | ||||||||||
HOMA-IR −0.8 | |||||||||||
HDL-C −1 | |||||||||||
Pilot study | 26 subjects, aged 18–55 y; BMI 30 kg/m2 | 8 | zero-calorie ADF (n = 14) | −8.2 | NA | SBP NA | TG −25 | FI +3 μU/mL FPG +6 HOMA-IR NA | No relevant safety changes over the 8-w; zero-cal ADF is safe and tolerable and not associated with weight regain after 24 w of follow-up | [159] | |
TC −31.8 | |||||||||||
DBP NA | LDL-C −22.6 | ||||||||||
HDL-C −4.2 | |||||||||||
CR (n = 12): −400 kcal/day | −7.1 | NA | SBP NA | TG −2.8 | FI −0.2 μU/mL FPG +3.3 HOMA-IR NA | ||||||
TC −21.7 | |||||||||||
DBP NA | LDL-C −16.9 | ||||||||||
HDL-C −4.2 | |||||||||||
Randomized controlled trial NCT00960505 | 79 subjects, BMI 25–40 kg/m2; men and women aged 18–65 y | 24 (12 control feeding period, 12 self-selected feeding) | ADF (n = 25) alternating every 24 h between consuming 25% or 125% of energy needs | NA | NA | SBP NA | TG NA | FI −7.4 μIU/mL | NA | [163] | |
TC NA | |||||||||||
FPG 0 | |||||||||||
DBP NA | LDL-C NA | ||||||||||
HOMA-IR −1.88 | |||||||||||
HDL-C NA | |||||||||||
CR (n = 29) consuming 75% of needs every day | NA | NA | SBP NA | TG NA | FI −4.4 μIU/mL | ||||||
TC NA | |||||||||||
FPG +5.2 | |||||||||||
DBP NA | LDL-C NA | ||||||||||
HOMA-IR −0.79 | |||||||||||
HDL-C NA | |||||||||||
CONTROL (n = 25) consuming 100% of needs every day | NA | NA | SBP NA | TG NA | FI +0.6 μIU/mL | ||||||
TC NA | |||||||||||
FPG +5.2 | |||||||||||
DBP NA | LDL-C NA | ||||||||||
HOMA-IR +0.5 | |||||||||||
HDL-C NA | |||||||||||
Randomized, controlled, long-term study NCT02480504 | 112 subjects, aged 21–70 y; BMI 30–45 kg/m2 | 1 y (6 months weight loss, 6 months weight maintenance) | 5:2 approach consumption of 400/600 kcal (female/male) on each of two nonconsecutive days a week and to consume food as usual the remaining five days a week | −9.1 | −8 | SBP −1.9 | TG −0.31 mmol/L | FI NA | None of the participants withdrew. Participants in the IF group reported stronger feelings of hunger. Adverse events and larger weight regain than in the CR group | [167] | |
TC +0.7 mmol/L | |||||||||||
FPG −0.2 mmol/L | |||||||||||
DBP −3 | |||||||||||
LDL-C −0.03 mmol/L | |||||||||||
HOMA-IR NA | |||||||||||
HDL-C +0.13 mmol/L | |||||||||||
CR reduction in energy intake seven days a week | −9.4 | −9.2 | SBP −3.6 | TG −0.11 mmol/L | FI NA | ||||||
TC +0.17 mmol/L | |||||||||||
FPG 0 mmol/L | |||||||||||
DBP −2.9 | |||||||||||
LDL-C +0.08 mmol/L | |||||||||||
HOMA-IR NA | |||||||||||
HDL-C +0.13 mmol/L | |||||||||||
Single-center, parallel group randomized controlled trial ACTRN12614000396628 | 23 males, aged 55–75 y, BMI ≥ 30 kg/m2 | 6 months | 5:2 approach n = 11 restricted daily calorie intake to 600 cal on the fast day for two non-consecutive days per week and eat ad libitum on the remaining 5 days | −5.3 | −8 | SBP −14 | TG −0.3 mmol/L | FI NA | No adverse side effects experienced in either dietary group. Over half of participants on the 5:2 diet experienced hunger after 2 w with slight progress over time- Compliance rates were similar in both dietary groups | [164] | |
TC 0 mmol/L | |||||||||||
FPG −0.1 mmol/L | |||||||||||
DBP −0.2 | LDL-C −0.09 mml/L | ||||||||||
HOMA-IR NA | |||||||||||
HDL-C +0.04 mmol/L | |||||||||||
SERD (standard energy-reduced diet) n = 12 continuous daily energy-restricted diet (500- cal daily reduction from average requirement) | −5.5 | −6.4 | SBP −10.2 | TG −0.2 mmol/L | FI NA | ||||||
TC +0.2 mmol/L | |||||||||||
FPG −0.2 mmol/L | |||||||||||
DBP −3.7 | LDL-C −0.45 mmol/L | ||||||||||
HOMA-IR NA | |||||||||||
HDL-C 0 mmol/L | |||||||||||
Randomized, controlled, parallel-arm diet trial NCT0365253 | 31 subjects, aged 20–65 y; BMI >23 kg/m2 | 8 | E-ADF (ADF and exercise) 25% of daily recommended energy intake (approximately 500 kcal) on each fast day (24 h), and food ad libitum on each feed day (24 h). The fast day and feed day were repeated every other day, and the fast day occurred 3 days per week. Exercise-training and aerobic exercise. | −3.9 | NA | SBP NA | TG −43.6 | FI −3.87 μIU/mL | NA | [168] | |
TC +15.1 | |||||||||||
FPG −14.1 | |||||||||||
DBP NA | LDL-C +17.8 | ||||||||||
HOMA-IR −1.12 | |||||||||||
HDL-C +6 | |||||||||||
ADF 25% of daily energy intake (approximately 500 kcal) on each fast day (24 h), and food ad libitum on each feed day (24 h). The fast day and feed day were repeated every other day, and the fast day occurred 3 days per week | −3.9 | NA | SBP NA | TG +12.6 | FI +3.21 μIU/mL | ||||||
TC +5.4 | |||||||||||
FPG −9.7 | |||||||||||
DBP NA | |||||||||||
LDL-C 0 | |||||||||||
HOMA-IR +0.68 | |||||||||||
HDL-C +2.9 | |||||||||||
EXERCISE exercise intervention included resistance training and aerobic exercise. | −2 | NA | SBP NA | TG −87.9l | FI +0.04 μIU/mL | ||||||
TC +20.3 | |||||||||||
FPG −1.3 | |||||||||||
DBP NA | LDL-C +26.7 | ||||||||||
HOMA-IR +0.01 | |||||||||||
HDL-C +11.2 | |||||||||||
CONTROL | −0.2 | NA | SBP NA | TG +53.2 | FI +5.19 μIU/mL | ||||||
TC +33.2 | |||||||||||
FPG −4 | |||||||||||
DBP NA | LDL-C +16.9 | ||||||||||
HOMA-IR +1.10 | |||||||||||
HDL-C +5.7 | |||||||||||
Longitudinal study | 31 subjects, BMI 30–49.9 kg/m2; aged 18–65 y | 6 months (3 months weight-loss, 3 months weight-maintenance) | ADF low-carbohydrate intervention | −5.5 | NA | SBP −7 | TG −14 | FI −4 μIU/mL | Adherence was high amongst those who completed the study. High dropout (40%), particularly in the first few months of intervention | [165] | |
TC −12 | |||||||||||
FPG 0 | |||||||||||
DBP −4 | LDL-C −10l | ||||||||||
HOMA-IR −0.7 | |||||||||||
HDL-C −2 | |||||||||||
T2DM | Non-blinded randomized parallel group interventional trial ACTRN12614000402640 | 37 subjects aged >18 y with T2DM treated with metformin and/or any combination of hypoglycemic agents, HbA1c 50–86 mmol/mol; 15 females and 22 males. | 12 | Diet with consecutive fasting days (n = 18) | −3.1 | −1.6 | SBP −3 | TG +0.1 mmol/dL | FI NA | Hypoglycemic events (53) during 84 days of observation affecting 15 participants which required further medication adjustments in 9 out of 37 subjects | [170] |
TC +0.1 mmol/dL | |||||||||||
FPG −1.3 mmol/dL | |||||||||||
DBP −2 | LDL-C +0.15 mmol/dL | ||||||||||
HOMA-IR NA | |||||||||||
HDL-C +0.1 mmol/dL | |||||||||||
Diet with non-consecutive fasting days (n = 19) | −3.6 | −3.4 | SBP −4 | TG 0.1 mmol/dL | FI NA | ||||||
TC −0.4 mmol/dL | |||||||||||
FPG −1.1 mmol/dL | |||||||||||
DBP −3 | |||||||||||
LDL-C −0.1 mmol/dL | |||||||||||
HOMA-IR NA | |||||||||||
HDL-C 0 mmol/dL | |||||||||||
NCT00960505 | 43 insulin-resistant individuals, aged 18–65 y, BMI 25–39.9 kg/m2 | 12 months | ADF (n = 11)
| −8 | NA | SBP −9 | TG −27 | FI −12 μIU/mL | ADF participants consumed almost twice as many calories on fast days but still observed greater metabolic effects compared with CR participants | [171] | |
TC +4 | |||||||||||
FPG −3 | |||||||||||
DBP −5 | LDL-C +7 | ||||||||||
HOMA-IR −3 | |||||||||||
HDL-C +3 | |||||||||||
CR (n = 17)
| −5 | NA | SBP −7 mmHg | TG −6 | FI −1 μIU/mL | ||||||
TC −6 | |||||||||||
FPG −4 | |||||||||||
DBP −2 | LDL-C −6 | ||||||||||
HOMA-IR −0.9 | |||||||||||
HDL-C +2 | |||||||||||
CONTROL (n = 15) not changing usual eating and activity habits | 0 | NA | SBP −1 | TG −8 | FI −3 μIU/mL | ||||||
TC −1 | |||||||||||
FPG +4 | |||||||||||
DBP −3 | LDL-C 0 | ||||||||||
HOMA-IR 0.5 | |||||||||||
HDL-C +2 | |||||||||||
Randomized controlled clinical pilot study | 32 subjects, aged 25–75 y with a manifest and treated T2DM | 7 days of intervention 4 months trial | ADF n = 16 2 pre-fasting days with moderate caloric restriction (approx. 1200 kcal) followed by 7 modified fasting days with nutritional energy intake of 300 kcal/day by liquids only and subsequent stepwise re-introduction of ordinary food items over 3 days | −3.5 | −4.4 | SBP −13.9 | TG −26.6 | FI −3.5 μU/mL | Fasting was well accepted, no serious adverse events | [169] | |
TC −0.5 | |||||||||||
FPG −10.6 | |||||||||||
DBP −9 | LDL-C −2.6 l | ||||||||||
HOMA-IR −1.5 | |||||||||||
HDL-C +6.5 | |||||||||||
CONTROL n = 16 following the principles of a Mediterranean diet | −2 | −0.3 | SPB +0.4 | TG −2.5 | FI −0.2 μU/mL | ||||||
TC −15.5 | |||||||||||
FPG −38.4 | |||||||||||
DBP +3.2 | LDL-C −7.8 | ||||||||||
HOMA-IR −1.5 | |||||||||||
HDL-C −2.3 | |||||||||||
Metabolic syndrome | Single-center, randomized clinical trial IRCT201509092395N8 | 69 subjects, aged 25–60 y overweight (BMI 25–40 kg/m2), 41 males and 28 females diagnosed with MetS | 8 | ADF n = 35 75% energy restriction during 3 fast days and 100% of energy needs on feed day | −4.1 | −4 | SBP −13 | TG −52 | FI −2.41 μU/mL | no complaint due to difficulties with diet adherence | [172] |
TC −11 | |||||||||||
FPG −5 | |||||||||||
DBP −8 | LDL-C −5 | ||||||||||
HOMA-IR −0.72 | |||||||||||
HDL-C 0 | |||||||||||
CR n = 34 75% of energy needs each day | −1.7 | −1 | SBP −1 | TG −40 | FI −1.56 μU/mL | No complaint due to difficulties with diet adherence | |||||
TC −8 | |||||||||||
FPG 0 | |||||||||||
DBP −5 | LDL-C −1 | ||||||||||
HOMA-IR −0.39 | |||||||||||
HDL-C 0 | |||||||||||
Randomized controlled trial NCT03608800 | 39 subjects with MetS, 21 males and 18 females aged 30–50 y | 8 | ADF n = 21 75% energy restriction for 2 non-consecutive days a week and an ad libitum diet the other 5 days | −3.5 | −2.5 | SBP −5.3 | TG –0.22 | FI NA | 91.3% of participants were compliant | [173] | |
TC –0.04 | |||||||||||
FGP NA | |||||||||||
DBP −2.5 | LDL-C +0.02 | ||||||||||
HOMA-IR −0.75 | |||||||||||
HDL-C +0.5 | |||||||||||
CONTROL n = 18 routine diet without dietary instructions | −1.2 | −1.1 | SBP −4.9 | TG 0 | FI NA | 78.3% of participants were compliant | |||||
TC −0.27 | |||||||||||
FGP NA | |||||||||||
DBP −2.1 | LDL-C +0.55 | ||||||||||
HOMA-IR −0.09 | |||||||||||
HDL-C +0.16 |
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Brogi, S.; Tabanelli, R.; Puca, S.; Calderone, V. Intermittent Fasting: Myths, Fakes and Truth on This Dietary Regimen Approach. Foods 2024, 13, 1960. https://doi.org/10.3390/foods13131960
Brogi S, Tabanelli R, Puca S, Calderone V. Intermittent Fasting: Myths, Fakes and Truth on This Dietary Regimen Approach. Foods. 2024; 13(13):1960. https://doi.org/10.3390/foods13131960
Chicago/Turabian StyleBrogi, Simone, Rita Tabanelli, Sara Puca, and Vincenzo Calderone. 2024. "Intermittent Fasting: Myths, Fakes and Truth on This Dietary Regimen Approach" Foods 13, no. 13: 1960. https://doi.org/10.3390/foods13131960
APA StyleBrogi, S., Tabanelli, R., Puca, S., & Calderone, V. (2024). Intermittent Fasting: Myths, Fakes and Truth on This Dietary Regimen Approach. Foods, 13(13), 1960. https://doi.org/10.3390/foods13131960