Health Effects of Intermittent Fasting Hormesis or Harm? A Systematic Review
ABSTRACT
Background: Intermittent fasting, alternating-day fasting, and other forms of periodic caloric desistance are gaining popularity in the lay press and among animal research scientists. Whether clinical show exists for or is stiff plenty to support the apply of such dietary regimens equally health interventions is unclear.
Objective: This review sought to identify rigorous, clinically relevant research studies that provide high-quality prove that therapeutic fasting regimens are clinically beneficial to humans.
Blueprint: A systematic review of the published literature through January 2015 was performed past using sensitive search strategies to identify randomized controlled clinical trials that evaluated the furnishings of fasting on either clinically relevant surrogate outcomes (e.g., weight, cholesterol) or actual clinical event endpoints [e.yard., diabetes, coronary avenue illness (CAD)] and any other studies that evaluated the effects of fasting on clinical event outcomes.
Results: 3 randomized controlled clinical trials of fasting in humans were identified, and the results were published in v manufactures, all of which evaluated the effects of fasting on surrogate outcomes. Improvements in weight and other take chances-related outcomes were plant in the 3 trials. Ii observational clinical outcomes studies in humans were found in which fasting was associated with a lower prevalence of CAD or diabetes diagnosis. No randomized controlled trials of fasting for clinical outcomes were identified.
Conclusions: Clinical enquiry studies of fasting with robust designs and high levels of clinical evidence are sparse in the literature. Whereas the few randomized controlled trials and observational clinical outcomes studies back up the being of a health benefit from fasting, substantial farther research in humans is needed before the use of fasting as a wellness intervention can be recommended.
INTRODUCTION
Caloric restriction (CR)5 and total caloric desistance [TCD; i.e., intermittent fasting, alternate-solar day fasting (ADF), routine periodic fasting, or intermittent energy restriction] are methods of energy deprivation (1–4). CR dramatically improves metabolic health and many other physiological and molecular markers of health and longevity (1), and TCD may also bear upon health. Animal models of CR and TCD have shown that limitations in free energy intake extend longevity (5–7) and reduce the risk of atherosclerosis, metabolic dysregulation, and cognitive dysfunction (four, five, eight–18). Whereas CR is better established for improving chance profiles (1), the basis for studying fasting approaches such equally ADF—in office—is that compliance with the regimen may be greater. This is considering of the periodic nature of fasting, which mitigates the abiding hunger that practitioners of CR endure. Both CR and TCD require farther inquiry, only if the health benefits of TCD are at least as stiff as those of CR, the less frequent but more than intense energy impecuniousness of TCD may be preferred.
The case for a human health benefit is simply beginning to exist made. TCD may provide non just a greater dose of CR but powerful metabolic effects. Furthermore, TCD and CR may provide some of their health benefits through singled-out pathways (4, 5, 8). Unfortunately, diverse fasting fad diets accept appeared in the popular press, and the lines between these and valid research have get blurred (19). The vast majority of fasting research has been in animals, and evidence in humans of wellness improvements from fasting is preliminary.
Mechanistic explanations for the benefits from TCD include the post-obit: 1) the body uses fats for energy during TCD, reducing adipose mass and resulting in a small, long-term reduction in risk afterwards each fasting episode (12, 20–23); and 2) nutritional stress during TCD, at to the lowest degree in office, results in cellular-level repairs, functional optimization, and metabolic rejuvenation (4, 9–11) that may improve long-term wellness by reducing cardiovascular risk factors (4, ten, 18) and acting on the metabolism of glucose via Forkhead Box A genes (5, 8, 12, 24). In some brute models, TCD is at least every bit proficient as CR at improving markers of metabolic health (4, 10). TCD-associated cerebral performance has been extensively evaluated in animals (4, 12–18), including its use to reduce circulating concentrations of brain-derived neurotrophic gene (16).
Various human TCD regimens—traditionally called fasting (which volition be used in the residual of the review)—such every bit ADF are being evaluated. In ADF, participants fast every other day and eat ad libitum on in-between days (25). In some other regimen, fasting occurs twice per week on nonconsecutive days (26). Well-nigh human fasting interventional trials accept been for the primary endpoint of weight loss and have not used control arms (some used multiple noncontrol energy-restriction regimens). Pocket-size studies of obese and nonobese individuals plant that weight was lower past 2.5–8% after iii–8 wk of ADF (25, 27–29). In a larger 3-mo study, weight was 6.3% lower later the twice-weekly regimen (26). Fasting also may improve other endpoints such as cardiovascular and metabolic take chances profiles (twenty, 25, 26, 28, xxx–32), but many of those changes would non remain significant if corrected for multiple comparisons.
This review evaluated the clinical evidence in humans that fasting is beneficial, including from randomized controlled trials of the furnishings of fasting on clinically relevant surrogate outcomes (e.g., weight and cholesterol) or actual clinical effect endpoints [e.g., diabetes and coronary artery disease (CAD)] and whatsoever other studies of clinical event outcomes.
METHODS
A systematic review of the literature was performed by searching computerized databases for published, peer-reviewed articles in English. Searches included the terms "intermittent fasting," "alternate-day fasting," "periodic fasting," and "intermittent free energy restriction." In improver, the reference lists of articles identified to exist related to fasting were examined for other trials or studies that were relevant.
The master aims were to 1) place randomized clinical trials of fasting in which a standard diet or noninterventional command group was used and 2) find all studies in which the inquiry endpoint was the clinical consequence, such as diagnosis of diabetes, CAD, or cognitive impairment such as dementia (regardless of whether it was a clinical trial). Filters were also used for "humans" to eliminate animal studies and—for aim 1—"clinical trial" to eliminate clinical studies that did not accept a command arm. Randomized trials with multiple interventional arms (eastward.g., an intermittent fasting arm and a CR arm) but no usual diet control arm were considered to be incomplete trials and were not counted as controlled trials of fasting. Because intermittent fasting and CR have not been conclusively proven to have benign effects in humans with acceptable safety profiles (1), they were not considered to be controls for trials that were identified. Studies whose endpoints were surrogate outcomes (e.g., weight loss, LDL cholesterol, and encephalon-derived neurotrophic gene) that themselves are predictors of clinical events were not considered to exist clinical outcomes studies.
Searches for "intermittent fasting" identified 198 articles, including 83 studies in humans of which 8 were clinical trials. "Alternate-day fasting" searches identified 46 articles, of which 18 were in humans and 7 were labeled every bit clinical trials. For "periodic fasting," 19 articles were constitute: 9 in humans (including the only clinical outcomes studies that were institute) and just one that was called a clinical trial. The term "intermittent energy restriction" retrieved but 12 articles: eight in humans, of which only 2 were clinical trials.
From these searches, a total of only 3 randomized controlled clinical trials with standard diet or noninterventional controls were identified. The results of these 3 trials were published in 5 articles (one trial'due south results were published in iii articles). Furthermore, only 2 clinical outcomes studies were institute, both of which were prospective observational studies.
RESULTS
Evidence of a fasting benefit for humans based on surrogate outcomes studies
The 5 reports from 3 randomized, controlled trials of fasting that had a control consisting of a noninterventional or standard nutrition are shown in Table one. One of these trials was a 12-wk written report of weight loss in 32 nonobese individuals, which confirmed the loss of half dozen.v% of body weight in the ADF intervention arm compared with the nonfasting control arm (36). The study also reported improvements in other cardiovascular and metabolic variables such as triglycerides, LDL-cholesterol particle size, and C-reactive poly peptide, but it did not correct for multiple comparisons (a common scientific design problem of many fasting studies) (36). This study did non evaluate subject safety outcomes. Safety information for ADF regimens are lacking, but ADF has been shown to not cause an increase in caloric intake on nonfasting days, despite what some may await from the effects of prolonged hunger (39, 40).
Tabular array 1
Clinical studies of fasting that met this systematic review'southward inclusion criteria i
| First author (ref) | Year | Sample size | Type of fasting regimen | Length of regimen | Primary endpoint |
| Randomized controlled clinical trials of fasting (all were for surrogate outcomes) | |||||
| Teng (33) | 2011 | 25 | 2 d/wk + CR | 12 wk | Multiple two |
| Hussin (34) | 2013 | 32 | 2 d/wk + CR | 12 wk | Multiple 2 |
| Teng (35) | 2013 | 32 | 2 d/wk + CR | 12 wk | Multiple two |
| Varady (36) | 2013 | 32 | Alternate-day fasting | 12 wk | Weight loss |
| Horne (21) | 2013 | thirty | 24 h water only | two d | Multiple iii |
| Clinical event outcomes studies of fasting (both were observational) | |||||
| Horne (37) | 2008 | 445 | Primarily religious, ordinarily once per calendar month iv | Decades 5 | CAD diagnosis |
| Horne (38) | 2012 | 200 | Primarily religious, usually once per month 4 | Decades 5 | Diabetes diagnosis |
| First author (ref) | Year | Sample size | Type of fasting regimen | Length of regimen | Primary endpoint |
| Randomized controlled clinical trials of fasting (all were for surrogate outcomes) | |||||
| Teng (33) | 2011 | 25 | 2 d/wk + CR | 12 wk | Multiple 2 |
| Hussin (34) | 2013 | 32 | 2 d/wk + CR | 12 wk | Multiple 2 |
| Teng (35) | 2013 | 32 | ii d/wk + CR | 12 wk | Multiple 2 |
| Varady (36) | 2013 | 32 | Alternate-day fasting | 12 wk | Weight loss |
| Horne (21) | 2013 | 30 | 24 h water simply | ii d | Multiple three |
| Clinical event outcomes studies of fasting (both were observational) | |||||
| Horne (37) | 2008 | 445 | Primarily religious, usually in one case per calendar month 4 | Decades 5 | CAD diagnosis |
| Horne (38) | 2012 | 200 | Primarily religious, usually in one case per month 4 | Decades 5 | Diabetes diagnosis |
1 CAD, coronary artery disease; CR, caloric restriction; ref. reference.
2 No main endpoint was specified, and the results were not corrected for multiple hypothesis tests.
3 Bonferroni-corrected statistical significance at P ≤ 0.00167 (30 tests of hypothesis).
4 Fasting was per a personally defined regimen, but the vast majority fasted approximately once per month for religious reasons (43).
5 Specific length of regimen was not investigated, but the religious teaching is a life-long regimen after the age of viii y.
TABLE one
Clinical studies of fasting that met this systematic review's inclusion criteria 1
| First author (ref) | Year | Sample size | Type of fasting regimen | Length of regimen | Master endpoint |
| Randomized controlled clinical trials of fasting (all were for surrogate outcomes) | |||||
| Teng (33) | 2011 | 25 | ii d/wk + CR | 12 wk | Multiple two |
| Hussin (34) | 2013 | 32 | 2 d/wk + CR | 12 wk | Multiple ii |
| Teng (35) | 2013 | 32 | 2 d/wk + CR | 12 wk | Multiple 2 |
| Varady (36) | 2013 | 32 | Alternate-mean solar day fasting | 12 wk | Weight loss |
| Horne (21) | 2013 | 30 | 24 h water merely | 2 d | Multiple 3 |
| Clinical event outcomes studies of fasting (both were observational) | |||||
| Horne (37) | 2008 | 445 | Primarily religious, usually once per month four | Decades 5 | CAD diagnosis |
| Horne (38) | 2012 | 200 | Primarily religious, normally in one case per month 4 | Decades five | Diabetes diagnosis |
| Get-go writer (ref) | Yr | Sample size | Type of fasting regimen | Length of regimen | Master endpoint |
| Randomized controlled clinical trials of fasting (all were for surrogate outcomes) | |||||
| Teng (33) | 2011 | 25 | 2 d/wk + CR | 12 wk | Multiple 2 |
| Hussin (34) | 2013 | 32 | 2 d/wk + CR | 12 wk | Multiple 2 |
| Teng (35) | 2013 | 32 | 2 d/wk + CR | 12 wk | Multiple 2 |
| Varady (36) | 2013 | 32 | Alternate-day fasting | 12 wk | Weight loss |
| Horne (21) | 2013 | 30 | 24 h water only | 2 d | Multiple 3 |
| Clinical result outcomes studies of fasting (both were observational) | |||||
| Horne (37) | 2008 | 445 | Primarily religious, normally once per calendar month 4 | Decades 5 | CAD diagnosis |
| Horne (38) | 2012 | 200 | Primarily religious, usually once per calendar month 4 | Decades 5 | Diabetes diagnosis |
1 CAD, coronary artery disease; CR, caloric restriction; ref. reference.
ii No primary endpoint was specified, and the results were non corrected for multiple hypothesis tests.
iii Bonferroni-corrected statistical significance at P ≤ 0.00167 (xxx tests of hypothesis).
iv Fasting was per a personally defined regimen, just the vast majority fasted approximately one time per month for religious reasons (43).
v Specific length of regimen was not investigated, but the religious teaching is a life-long regimen later on the age of eight y.
Some of the weight-loss studies, including the i trial just mentioned and some noted in the introduction, evaluated metabolic, cardiovascular, and cognitive benefits as secondary outcomes. The other 4 reports of randomized controlled trials of fasting provide information for master outcomes other than weight.
The second randomized controlled trial of fasting was reported in 3 articles using the chief endpoints of "mood states and depression status" (34), "metabolic parameters and Deoxyribonucleic acid damage" (35), and "mood and quality of life" (33). 1 of these manufactures was published before full enrollment in the trial (33), used similar outcomes every bit one of the other manufactures (34), and will non be discussed. Overall mood—including components from tension, anger, and confusion—was improved by fasting in a written report of 32 subjects during 12 wk of the intervention phase. Unfortunately, correction for the 7 hypothesis tests of measures of mood was not done and would result in no finding being statistically meaning (34). From the same 12-wk trial just in another article, claret pressure, full cholesterol, LDL cholesterol, weight, fat mass, and other factors—including Dna damage measures—were changed by fasting (35). As before, no primary hypothesis was specified, and no correction for multiple comparisons was fabricated in what must be considered a subsequent analysis of the prior study (34). None of these reports evaluated safety outcomes for the trial (33–35).
The third randomized controlled clinical trial was the Fasting and Enhanced Expression of Longevity Genes during Food Abstinence (FEELGOOD) trial (21). It used a Latin-foursquare crossover design to examine simply one 24-h flow of fasting and i day of advertizement libitum feeding. FEELGOOD is the only randomized controlled trial of fasting to right for multiple comparisons (21). No primary endpoint was used, but P ≤ 0.00167 was the threshold for significance for 30 tests of hypothesis. In FEELGOOD, fasting induced marked but temporary increases in human growth hormone (HGH), cerise claret cell count (and hemoglobin and hematocrit), and total cholesterol [resulting from increases in both LDL cholesterol and HDL cholesterol, despite substantially decreased triglycerides, as establish in other fasting studies (41, 42)] (21). This trial evaluated simply 1 24-hour interval of fasting, and no safe outcomes were studied (21); thus, the findings are useful primarily in developing longer-term trials.
Fasting and major adverse clinical events
Two observational clinical events studies have examined fasting and major adverse clinical outcomes in humans. These epidemiologic studies of fasting began in 2001, based not on CR but on declining tobacco smoking. Smoking declined more from 1984 to 1996 in states such equally California than in Utah, where the smoking rate was already depression (43); however, mortality rankings were essentially unchanged over the same time flow (44). An initial study was performed challenging the assumption that Utah's low CAD chance was merely attributable to the proscription of smoking among members of the Church building of Jesus Christ of Latter-Day Saints (LDSs), or Mormons (37). That report establish that LDSs in Utah had a lower risk of CAD than did those of other religious preferences (adjusted OR: 0.81; 95% CI: 0.69, 0.95; P = 0.009), despite adjustment for smoking (37).
To amend understand the low CAD risk among LDS individuals, fasting history was evaluated during 2004–2006 amid 448 cardiac catheterization patients of unrestricted religious preference. Patients who reported routine fasting had a lower odds of CAD (adjusted OR: 0.46; 95% CI: 0.27, 0.81; P = 0.007) than did those who did not fast, despite extensive adjustment for potential confounders (37). Interestingly, those of religious preferences other than LDSs who reported routine fasting as well benefited: for CAD (OR: 0.23; 95% CI: 0.06, 0.90; P = 0.037) (37). A secondary finding (NS after correction for multiple comparisons) was that fasting was associated with a lower odds of diabetes (37).
A second observational clinical outcomes report confirmed and expanded on the fasting associations with CAD and diabetes. Using the same fasting survey question (37), a written report was conducted amongst 200 patients from 2007 to 2008 (38). This report evaluated a new set of cardiac patients for the primary event of diabetes, which was non significantly associated with fasting (after multiple-comparisons correction) in the starting time study (37) and, thus, required additional evaluation every bit the primary hypothesis examination (38). The second report found that patients who fasted routinely had lower odds of diabetes (adapted OR: 0.40; 95% CI: 0.16, 0.99; P = 0.044) and confirmed the offset study'southward findings for CAD (adjusted OR: 0.37; 95% CI: 0.18, 0.88; P = 0.019) (Figure 1) (38). In add-on, fasters had lower glucose concentrations and BMI (Figure ii) (38).
Effigy 1
The association of routine periodic fasting with prevalent diabetes and coronary artery disease in the electric current written report (n = 200) (38) and its association with outcomes in meta-analyses (n = 648) of this written report's population and 448 previously studied angiographically examined patients (37). ORs (from logistic regression) for fasting were adapted for age and sexual activity for the diabetes endpoint; those for the coronary artery disease endpoint were adapted for diabetes, age, sex, BMI, hypertension, hyperlipidemia, smoking, and family history of early coronary artery disease. Reproduced from reference 38 with permission.
Effigy 1
The clan of routine periodic fasting with prevalent diabetes and coronary artery disease in the current study (n = 200) (38) and its association with outcomes in meta-analyses (n = 648) of this report's population and 448 previously studied angiographically examined patients (37). ORs (from logistic regression) for fasting were adapted for age and sex for the diabetes endpoint; those for the coronary avenue disease endpoint were adjusted for diabetes, age, sex activity, BMI, hypertension, hyperlipidemia, smoking, and family unit history of early coronary avenue illness. Reproduced from reference 38 with permission.
Figure 2
Meta-assay box plots showing differences past fasting status in the distributions of serum glucose concentrations (A) (P = 0.047) and BMI (B) (P = 0.044) in the combined populations (meta-analysis, n = 648) of the electric current study (northward = 200) (38) and a previous fasting report (n = 448) (37). Comparisons to determine differences were made by using ANOVA. Reproduced from reference 38 with permission.
Effigy 2
Meta-analysis box plots showing differences by fasting status in the distributions of serum glucose concentrations (A) (P = 0.047) and BMI (B) (P = 0.044) in the combined populations (meta-assay, n = 648) of the current study (n = 200) (38) and a previous fasting study (n = 448) (37). Comparisons to determine differences were made past using ANOVA. Reproduced from reference 38 with permission.
DISCUSSION
For fasting to be more than a weight-loss fad, greater scientific rigor is needed from interventional trials than is found in the literature. Whereas enthusiasm for fasting is increasing, clinical relevance remains depression because of insufficient human data, including virtually nonexistent controlled trials (21, 33–36), few clinical outcomes studies (37, 38), lack of correction for inflated type I error rates from multiple hypothesis tests, and limited safety information (39–41). The evidence suggests, however, that therapeutic fasting may provide substantial do good for reducing clinical take chances.
Important metabolic and cardiovascular benefits have been reported in humans that deserve farther consideration in therapeutic fasting trials, such as decreases in fat mass, LDL-cholesterol particle size, LDL cholesterol, triglycerides, and C-reactive poly peptide (35, 36). Interestingly, whereas in the FEELGOOD trial LDL cholesterol increased during fasting (21), another study reported both college LDL cholesterol while fasting and lower LDL cholesterol after 6 wk of a fasting regimen (41, 42). Fasting also substantially increases HGH (21), facilitating lipolysis and fatty acrid release during fasting for use equally energy (22, 23). The dramatic effect of fasting on HGH ended soon afterward feeding resumed (21), only fasting may impact long-term health in function via periodic HGH-driven reductions in risk (23).
In addition to the various cardiovascular and metabolic findings, creature research strongly suggests that human being fasting studies of cognitive performance should exist conducted. Also, the frequency and duration of fasting requires farther investigation, including with regard to whether frequent episodes (e.g., i–4 times/wk) of therapeutic fasting should be washed.
Of farther annotation, despite the unlike designs, regimens, and study outcomes, the convergence of findings regarding fasting from the 2 epidemiologic clinical outcomes studies (that arose due to data regarding smoking and CAD outcomes, i.e., references 37 and 38) and the findings of interventional studies (most having arisen equally extensions of CR inquiry, i.e., references 20, 25–36, 39, twoscore) suggests that a prudent amount of fasting beneficially influences health outcomes. However, because the clinical outcomes studies involved observational epidemiologic research (37, 38), a randomized controlled clinical outcomes trial of fasting is needed to decide causality for clinical events.
On the point of observational compared with randomized trials, all of the previously mentioned interventional human studies of fasting (twenty–23, 25–36, 39–42) and most creature models of fasting have examined surrogate outcomes of cardiovascular, metabolic, and cognitive run a risk. A surrogate consequence, such as weight, glucose, or LDL cholesterol, is a gene that influences hazard of a clinical event such as CAD but that is not equivalent because some individuals with the hazard factor never feel the clinical event and some with the event do not have the risk gene. This is seen in information where the per centum of patients with and without CAD who accept high cholesterol, high blood pressure, and other surrogate outcomes is non 100% and 0%, respectively (45, 46). The effect of a wellness intervention on surrogate measures of risk is of only academic, nonclinical involvement if the treatment does not reduce subsequent major health events such as the onset of diabetes, dementia, and CAD. Unfortunately, some interventions that reduce surrogate endpoints may not affect the risk of disease or may even increment the risk of events. Examining major agin clinical events is a crucial step in determining whether an intervention is really beneficial.
Widely considered to exist the best tests of clinical efficacy and safety, the randomized, placebo-, or standard-controlled clinical trial has a rigorous design that is engineered to residual both observed and unmeasured confounders between the intervention and command arms, which makes any resulting difference observed betwixt the two trial arms a causal result of the intervention. Whereas this may be the optimal arroyo for studying the furnishings of fasting, no such randomized clinical trial has been performed. Furthermore, practical considerations make it unlikely that a fasting trial evaluating reductions in major adverse clinical events volition be conducted in the near future. These considerations include written report cost, the length of fourth dimension and sample size required, and the difficulty in keeping the control arm free from crossover to the intervention (or fasting arm subjects from ceasing the intervention) during the many years of the trial. In contrast, observational clinical studies (eastward.m., references 37, 38) tin provide the required information at a fraction of the cost and without the other concerns if statistical analyses appropriately accommodate for of import potential and known confounders. Historically, such considerations accept made it unnecessary to conduct randomized trials of some interventions for evaluation of clinical outcome outcomes (47).
The observational studies are express past a lack of a comprehensive dietary history; thus, residual confounding could remain (37, 38). Extensive adjustment was made in these studies for demographics, cardiac risk factors, physical activeness, income, and education too every bit factors that may differ between LDSs and other populations such as smoking, social support, frequency of church building omnipresence, and use of alcohol, tea, and coffee. Furthermore, the fasting regimen of most participants was a 24-h fast in one case per month; thus, different regimens (e.g., ADF) may have dissimilar (i.e., perhaps stronger) effects on CAD and diabetes. As well, genetic evaluations previously showed the Utah LDS population to be an outbred, continental population genetically similar to the U.s. Caucasian population (48, 49); thus, genetic differences are unlikely to explain the findings of the observational clinical events studies (50). It is also unclear whether fasting has an impact on CAD and diabetes in minority populations; thus, additional clinical events studies should exist performed amongst minorities.
Beyond efficacy, rubber data are critical for the therapeutic application of fasting simply are sorely lacking. Subsequently many weeks of continuous fasting (~v–7 wk in healthy adults), fasting converts into starvation, wherein vital organs and muscles are consumed for energy. Starvation causes excessive weight loss, anemia, chronic diarrhea, delirium, and other adverse reactions and eventually death. Intermittent therapeutic fasting should not accept these adverse effects, but it may still cause harm when proficient besides ofttimes or for too many days consecutively. Commonly, fasting may result in balmy adverse events such as headaches, fainting, weakness, aridity, and hunger pangs. More importantly, excessive fasting could pb to malnutrition, eating disorders, susceptibility to infectious diseases, or moderate damage to organs. In a study of rats, ADF was establish to upshot in increased left atrial diameter, myocardial fibrosis, and reduced cardiac reserve (51). Whereas left ventricular ejection fraction and ventricle size were not measurably afflicted by ADF, the observed changes suggest caution in the human application of regimens using frequent fasting (51). It may be that fasting multiple days or successive days per week is too frequent or intense for humans.
In conclusion, whether fasting really causes improvements in metabolic health, cognitive functioning, and cardiovascular outcomes over the long term; how much fasting is really beneficial; and where the threshold of hormesis resides (i.e., a balance between long-term benefit from fasting compared with damage from insufficient caloric intake) remain open questions. Unfortunately, the vast majority of human studies of a fasting intervention were weight-loss studies using single-arm, nonrandomized approaches or multiple intervention arms with no control. Whereas farther enquiry of CR is needed [e.k., the ongoing CALERIE Trial (52, 53)], considerable additional clinical research of fasting is required before contemplating changes to dietary guidelines or do. Dietary research has inherent challenges; thus, well-designed fasting trials of clinically relevant outcomes and populations are needed to avoid missteps [e.chiliad., contempo revision of 1980 guidelines on dietary fats and cholesterol (54–57)].
Future fasting research should determine whether and to what extent fasting regimens are safe. Further research is needed to decide whether fasting is constructive for improving health in the general population, higher-hazard people, and diseased individuals. Boosted knowledge is also needed regarding the mechanisms of benefit and the optimal frequency and elapsing of fasting in apparently healthy and high-take chances individuals. Finally, in deference to the current focus on lower-cost healthcare, fasting has no direct financial costs and represents a nominal savings on food expenses. In summary, intermittent fasting may better health; however, substantial boosted clinical inquiry is needed before advocating its use for health purposes.
The authors' responsibilities were as follows—BDH: designed and performed the review and wrote the manuscript; JBM and JLA: reviewed the manuscript; and BDH, JBM, and JLA: gave final approval for the manuscript. The authors had no financial conflicts of interest to report with respect to this work or its subject area affair.
FOOTNOTES
1 Supported by internal institutional funds.
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ABBREVIATIONS
-
ADF
-
CAD
-
CR
-
FEELGOOD
Fasting and Enhanced Expression of Longevity Genes during Nutrient Forbearance
-
HGH
-
LDS
-
TCD
© 2015 American Society for Nutrition
Source: https://academic.oup.com/ajcn/article/102/2/464/4564588
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