Introduction
Overweight and obesity are significant health challenges for women, with a substantial percentage of the female population in the UK living with these conditions. Energy-restricted diets are a cornerstone of managing overweight and obesity, but adherence to traditional daily energy restriction (DER) can be difficult to maintain over time, and the metabolic benefits may diminish. Intermittent energy restriction (IER) regimens have emerged as potential alternatives, aiming to improve adherence, promote sustained weight loss, and offer additional metabolic advantages. This article synthesizes the current research on IER diets, specifically focusing on their effects on women's health, comparing them with traditional DER approaches, and highlighting areas where further investigation is needed.
The Growing Problem of Overweight and Obesity in Women
In 2023, it was estimated that 61% of adult females in the UK were living with either overweight or obesity. Twenty-nine percent of these were living with obesity, which had increased from 26 % in 2013 and 23 % in 2003. Obesity estimates are based on BMI > 30 kg/m2 so are likely to underestimate the true impact of obesity related health conditions within ethnic groups since these groups experience obesity related comorbidities at a lower BMI than white women, that is, overweight is defined at 23-27 kg/m2 and obesity at 27 kg/m2 in these groups. Women from socially deprived backgrounds experience higher rates of obesity. Overweight and obesity amongst women are linked to higher risk of 11 cancers including breast and endometrial cancer. Obesity poses a greater cancer burden for women amongst whom 55 % of cancers are related to obesity compared to only 24 % of cancers among men.
Understanding Intermittent Energy Restriction (IER)
IER involves alternating periods of restricted energy intake with periods of normal eating. Several popular IER regimens have emerged, including:
- The 5:2 Diet: This involves consuming a low-energy diet (500-850 kcal/day) for two days per week, either consecutive or non-consecutive, and eating normally for the remaining five days.
- Alternate Day Fasting (ADF): This typically involves consuming a low-energy diet (500-650 kcal/day) for three to four days per week, interspersed with days of normal eating.
- Time-Restricted Eating (TRE): This involves limiting the eating window to 6-12 hours per day, with fasting periods of 12-18 hours. TRE can be ad libitum, where individuals eat freely during the eating window, or energy-restricted, where a daily energy-restricted diet is consumed within the defined eating window.
IER vs. Daily Energy Restriction (DER): A Comparative Analysis
Current evidence-based guidelines recommend daily energy restriction (DER), typically a 600 kcal energy deficit for sustainable weight loss. DER can be effective for weight loss but has reduced adherence over time. Also, the metabolic benefits of DER and weight loss are attenuated once weight is reduced and an individual is euenergetic, that is, in energy balance at a lower weight.
A recent meta-analysis, which included 11 randomized controlled trials (RCTs) and 850 participants (67% female), compared IER (5:2 or ADF) with energy-matched DER. The review concluded the three different IER diets resulted in comparable weight loss and cardiometabolic risk markers change compared with DER diets. However, a sub-group analysis in 7 studies which involved women only (n 507) showed IER had greater effects on reductions in body weight, body fat and waist circumference than DER. Body weight (weighted mean differences WMD -1·01 kg; 95 % CI: -1·52, -0·50), body fat (WMD: -1·08 kg; 95 % CI: -1·68, -0·48) and waist circumference (WMD: -1·40 cm; 95 % CI: -2·64, -0·15). No significant differences between IER and DER were observed in studies with men only or mixed cohorts.
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These results suggest superior short-term adherence and weight loss success with IER compared to DER.
Time-Restricted Eating (TRE) and Its Impact
TRE can either ad lib TRE which has an eating window but no prescribed energy restriction, or an energy-restricted TRE diet with a prescribed eating window. Ad lib TRE diets typically reduce energy intake by 200-300 kcal/d and are associated with a modest weight loss of 3 % in short-term studies and ∼1 % in longer-term studies. Studies of TRE diets v. matched energy-restricted diets consumed across the day have reported both superior or equivalent weight loss with TRE. Some potential weight independent metabolic benefits have been reported when TRE has an early eating window and avoids the adverse metabolic effects of late-night eating.
Metabolic Benefits of IER: Beyond Weight Loss
A key question is whether IER confers additional weight-independent effects on metabolic health, as evidenced by markers such as blood pressure, lipids, and insulin resistance. IER may have short-term beneficial effects on these markers during the repeated spells of energy restriction each week. In addition, there could be more sustained beneficial effects across the week if for example there were preferential reductions in body fat and ectopic fat stores with IER v. DER. Current evidence does not however support this assertion. Shubel et al reported equivalent weight loss parallelled with proportional reductions in visceral and subcutaneous fat stores with IER v. DER. Cioffi et al reviewed 11 RCTs of 5:2, ADF (not TRE) studies including 630 patients (range 8-24 weeks) and concluded there were small favourable differences in metabolic markers with IER v. DER. These effects were modest and of doubtful clinical significance, that is, IER had 0·05 mmol/l (3 %) higher HDL and 0·9 mmol/l (15 % greater reductions in insulin) than DER. These beneficial effects were mainly reported in short-term studies and may simply reflect slightly greater weight loss in these studies.
Factors Affecting Adherence and Weight Loss in Women
Lower dietary adherence and weight loss across a range of behavioural weight loss interventions have been reported amongst women v. men, amongst younger v. older subjects and amongst parents with children living at home. Consistent with this data adherence and weight loss success with 12 weeks of ADF has been reported to be lower amongst premenopausal women (-4·6 ± 3·2 %) compared to postmenopausal women (-6·5 ± 3·2 %) and men (-6·2 ± 4·4 %).
Cyclic changes in hormones in premenopausal women are likely to influence appetite and energy expenditure and dietary adherence across each month. Energy intake is often increased in the luteal phase due to cravings for high fat and/or carbohydrate foods, making this a potentially challenging time for adherence to a low energy diet for some women. Adherence to the different IER diets across the menstrual cycle is not known. However a menstrual cycle adapted DER weight loss programme which attempted to align with these cyclic variations has had limited success compared to a standardised DER across the month. Premenopausal women are reported to have a greater lipolytic response and higher plasma free fatty acids with extended overnight fasting compared to men and postmenopausal women which has a negative impact on postprandial glycaemia, summarised in.
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Potential Risks and Considerations
One concern is whether IER leads to greater loses of fat free mass (FFM) for a given weight loss than seen with DER. In people with overweight/obesity around 25 % of weight loss with daily energy-restricted diets is loss of FFM. IER could lead to greater reductions in FFM for a given weight loss as a result of spontaneous decreases in physical activity during energy-restricted periods, insufficient protein intakes, or sub-optimal regularity of protein intake to optimise muscle protein synthesis; the latter being particularly relevant with TRE. Greater losses of FFM with energy restriction are seen amongst subjects with lower fat mass, that is, lean compared to those with overweight/obesity, men compared to women, and alongside more severe energy/protein restriction, and in older subjects.
There are no data on the effects of IER on FFM in cohorts of healthy weight women who will be more susceptible to reductions in FFM than women with overweight or obesity. However, several studies report large reductions of FFM in groups of lean men and women exposed to ADF with alternate day 24-hour fasts. In the absence of data, it is prudent to advise adequate protein and exercise alongside IER diets. Exercise is well known to attenuate loss of FFM with energy-restricted diets.
Weight loss with energy-restricted diets in individuals with overweight or obesity can reduce bone quantity, bone density and bone quality. The latter is already compromised in subjects with obesity. Bone effects may be partly through reduced mechanical loading at a reduced weight and may also relate to increased bone marrow adipose tissue and associated cytokine production and adipokines and reduced osteoblast formation. Weight loss has been associated with reductions in total hip bone mineral density (BMD), but not lumbar spine BMD. The effects of 5:2, ADF and TRE on bone health are not known, nor whether they differ from those of DER. IER could exert detrimental effects on bone health alongside reduced physical activity during the energy-restricted spells of intermittent diets. In addition, elevated post-prandial insulin resistance in response to the first post fast meal consumed with IER has the potential to supress concentrations of C-terminal telopeptide and osteocalcin. One of the few data on IER and bone reported that 6 months of ADF or DER both resulted in a weight loss of 8 % and that neither diet was associated with reductions in total body dual energy x-ray absorptiometry (DXA) measured bone mineral density, or in circulating bone turnover markers osteocalcin, bone alkaline phosphatase or C-terminal telopeptide. This study has limitations and is likely to be underpowered for these bone measures, and it did not collect specific hip/spine BMD responses.
IER for Adolescents with Obesity
Both groups had a reduction in the occurrence of insulin resistance (from 52 of 68 [76.5%] to 32 of 56 [57.1%] in the IER group and from 59 of 68 [86.8%] to 31 of 60 [57.1%] in the CER group) at week 16; however, at week 52, this effect was observed in the CER group only (from 59 of 68 [86.7%] to 30 of 49 [61.2%]). The occurrence of dyslipidemia was unchanged between baseline and week 52 (60 of 137 [42.6%] and 37 of 87 [42.5%], respectively), with a small improvement in occurrence of impaired hepatic function tests (37 of 139 [27.0%] and 15 of 87 [17.2%], respectively). These findings suggest that intermittent and continuous energy restriction delivered as part of an intensive behavioral weight management program may both be beneficial options to improve weight and cardiometabolic outcomes for adolescents.
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