Wilkinson MJ, Manoogian ENC, Zadourian A, et al. Ten-hour time-restricted eating reduces weight, blood pressure, and atherogenic lipids in patients with metabolic syndrome. Cell Metab. 2020;31(1):92-104.
Animal studies show that time-restricted feeding (TRF) prevents and reverses metabolic diseases. Human studies have suggested time-restricted eating (TRE) reduces risk of metabolic diseases in healthy individuals. Prior to the study reviewed here, TRE had not yet been tested in patients already being treated for metabolic syndrome. This study sought to determine whether TRE could benefit these situations when employed in combination with standard therapies.
A single-arm, paired-sample trial
Twenty-five participants were enrolled in the trial, but only 19 (13 men and 6 women) were included in the final analysis. All were recruited from University of California San Diego (UCSD) clinics and had been diagnosed with metabolic syndrome. The majority of the participants were on a statin and/or antihypertensive therapy. All met a minimum of 3 of the criteria for metabolic syndrome. At baseline, the mean daily eating window of participants was ≥14 hours.
The participants underwent 10-hour TRE for 12 weeks. They had to eat all their food for the day within a 10-hour period.
A battery of laboratory tests and clinical measurements used to characterize metabolic syndrome were tracked in study participants, including body weight, body mass index (BMI), percent body fat, waist circumference, blood pressure, lipids, inflammatory markers, cardiometabolic factors (such as blood glucose, hemoglobin A1c, fasting insulin, and homeostatic model assessment of insulin resistance [HOMA-IR]), sleep and activity, thyroid function, and complete blood count (CBC).
Nearly all markers of metabolic disease improved significantly during the intervention. Participants experienced improved sleep as well as a 3%-4% reduction in body weight, BMI, abdominal fat, and waist circumference. Major risk factors for heart disease were diminished as participants showed reduced blood pressure and total cholesterol. Blood sugar levels and insulin levels trended toward improvement.
Metabolic syndrome is defined by the presence of multiple risk factors for type 2 diabetes mellitus (DM-2) and cardiovascular disease (CVD). It’s a common condition, affecting nearly one-third of the US population. Metabolic syndrome increases risk of diabetes by a factor of 5 and doubles risk of developing CVD in 5-10 years. We are familiar with the common features of this condition, which include abdominal obesity, high blood pressure, insulin resistance, inflammatory and thrombotic tendencies, and dyslipidemia. Standard interventions include weight loss, calorie restriction, and exercise. Pharmacotherapy is often used and includes lipid-lowering statins and drugs, such as metformin, to increase insulin sensitivity. TRE is an emerging dietary intervention that may elicit greater compliance than rigorous weight-loss and exercise programs. The data from this study suggests a synergistic effect when patients use TRE in combination with standard therapies.
This study focused on eating duration—that is the number of hours between the first time and last time a person consumes any calories during the 24-hour day.
In recent years we have become aware that the health impact of food is not only a matter of what people eat but also of when they eat, especially in relation to their sleep cycle.
In animal studies, this is referred to as time-restricted feeding. In humans, who feed themselves, the name is changed to time-restricted eating. Also note that TRE is the flip side of what is called nighttime fasting. In Catherine Marinac’s paper on nighttime fasting and breast cancer risk, benefit was associated with nighttime fasting for 13 hours or more per night as compared to 12 hours or less.1
In this current study, the clock is flipped, and researchers count the total daily interval in which participants consume meals instead of the time spent not eating. Thus, a 10-hour time-restricted eating intervention could also be described as a 14-hour nighttime fast. The difference, though, is that framing the diet in terms of eating may sound more appealing to patients than fasting. This change of names may increase the likelihood that a patient will try following this protocol, although this is speculative.
In recent years we have become aware that the health impact of food is not only a matter of what people eat but also of when they eat, especially in relation to their sleep cycle. The current theories suggest this effect is related to the circadian cycle.
The body is more efficient at digesting food and drink when a person is active and when light is present. Eating or drinking at night, when it is dark, appears to disrupt the body’s systems and impact metabolism negatively. A consistent daily cycle of eating and fasting nurtures the circadian clock to optimize metabolism.
At least in rodents, a regular schedule of eating and fasting keeps them healthier.2
There is a lot of interest in a number of eating strategies that emphasize calorie reduction, including calorie restriction (CR) and intermittent fasting (IF). These strategies are likely to influence the daily eating duration, even if people do not change that duration consciously. However, TRE doesn’t purposefully limit calorie intake. Let’s take a moment to sort through these various strategies.
Calorie restriction (CR)
We are probably most familiar with this strategy. Animal studies employ a simple reduction of daily calories. In rodent studies, this is usually accomplished by feeding the rodents a single daily meal with up to a 40% reduction in calories compared with regular intake; they usually consume the meal within 2 to 4 hours, leaving about 20 hours of the day without food. In humans, CR is usually practiced by reducing daily calories by up to 25%, often with no specific timing. The benefits of reduced calorie intake are well studied, whereas the influence of the short eating-duration period that may result from eating less per day has not been studied in contrast to simple CR. Therefore, it is unclear if the benefits of CR are in part due to the timing of calories or simply the total intake.
Intermittent fasting (IF)
This involves reducing calorie intake for various periods of time. There are several popular IF strategies including:
- Alternate-day fasting: complete fasting (water only) every other day.
- Alternate-day modified fasting: modified fasting every other day, which typically involves reducing calorie intake by 25% to 50%.
- Periodic fasting: complete fasting days, typically once per week or a few days per month. Consuming a low-calorie diet (typically <1,000 kcal daily) for 3 to 5 consecutive days every 2 to 3 months is also considered periodic fasting. The 5:2 diet is a specific version of periodic fasting, typically including 5 days without calorie restriction and 2 days of modified fasting each week.
During extended fasts, the body uses stored fat for energy, increasing ketone levels. Research documents a range of health benefits from calorie restriction as well as from fasting.3,4
Time-restricted feeding/eating (TRF/TRE) is different from these caloric-restriction strategies as there is no requirement to reduce caloric intake. It just requires consistently limiting consumption to a specific time interval. The evidence to date suggests that this alone may improve metabolism and cardiovascular health by improving circadian clock function.5 The benefit in treating diabetes suggested by this current study is consistent with data from research on mice.6 Benefits from TRE occur even without weight loss.7
This is far from simple, as the adoption of any culturally unusual diet may be difficult to achieve. With this in mind, Valter Longo suggested in a 2016 paper that various eating patterns may mimic the metabolic changes from fasting and be useful in designing “fasting-mimicking diets,” an idea that was borne from the high dropout rate of participants in clinical trials on fasting.8
We are slowly starting to have an idea of what to tell patients about meal timing based on evidence. At least based on mice research, it is probably better to eat our largest meals, particularly our high-fat meals, during our active, daytime period. Allowing mice to consume high-fat meals during their rest period encouraged metabolic disease. In humans, eating close to when melatonin begins to rise leads to greater fat deposition. Eating earlier in the day leads to greater weight loss in women.
Insulin sensitivity is greater in the morning. Our bodies process larger meals more effectively in the first half of the day. Melatonin reduces insulin release, so the body has a harder time processing glucose at night or early in the morning when melatonin is still elevated.9 Thus, we should be encouraging patients to eat larger meals earlier in the day and to avoid eating for a few hours before bed.2 The study reviewed here focused on “eating duration,” that is, the number of hours between the first and last time patients consumed any calories during a 24-hour period.
What we should tell people about breakfast remains complicated. Skipping breakfast is probably not a great idea, as studies find that doing so is associated with increased risk for DM-2, obesity, and CVD.10,11 These same studies suggest that breakfast skipping is associated with late-night eating, variable eating patterns, increased high-fat/high-sugar snacking, and reduced fruit and vegetable consumption. So maybe skipping breakfast is not the problem as much as what breakfast-skippers choose to eat the rest of the day. Asking patients if they skip breakfast might be a screening question that reveals a pattern of poor lifestyle choices. At the same time, the standard American breakfast is far from perfect. Americans are perhaps unique in the world; we have a very specific and limited image of what we think breakfast foods are. People in the rest of the world select from a far wider range of food choices for their first meal of the day than Americans do. People might be far better off substituting what they eat for dinner for their breakfast. Yet to do so would require changing deeply ingrained beliefs that might not be easily amenable to change.12
Given the results in this study by Wilkinson et al, we clearly have a new and novel strategy of treatment to employ in patients with metabolic syndrome and probably type-2 diabetes. The simplicity, lack of cost, and obvious safety highly recommend we encourage many of our patients to use it. As calorie-restriction strategies are now suggested for a wide range of conditions, in time evidence may suggest TRE is beneficial for an equally wide range of conditions beyond metabolic disorders.
- Marinac CR, Nelson SH, Breen CI, et al. Prolonged nightly fasting and breast cancer prognosis. JAMA Oncol. 2016;2(8):1049-1055.
- Manoogian ENC, Chaix A, Panda S. When to eat: the importance of eating patterns in health and disease. J Biol Rhythms. 2019;34(6):579-581.
- Mattson MP, Longo VD, Harvie M. Impact of intermittent fasting on health and disease processes. Ageing Res Rev. 2017;39:46-58.
- Golbidi S, Daiber A, Korac B, Li H, Essop MF, Laher I. Health benefits of fasting and caloric restriction. Curr Diab Rep. 2017;17(12):123.
- Panda S. The arrival of circadian medicine. Nat Rev Endocrinol. 2019;15(2):67-69.
- Hatori M, Vollmers C, Zarrinpar A, et al. Time-restricted feeding without reducing caloric intake prevents metabolic diseases in mice fed a high-fat diet. Cell Metab. 2012;15(6):848-860.
- Sutton EF, Beyl R, Early KS, Cefalu WT, Ravussin E, Peterson CM. Early time-restricted feeding improves insulin sensitivity, blood pressure, and oxidative stress even without weight loss in men with prediabetes. Cell Metab. 2018;27(6):1212-1221.
- Longo VD, Panda S. Fasting, circadian rhythms, and time-restricted feeding in healthy lifespan. Cell Metab. 2016;23(6):1048-1059.
- Forrestel AC, Miedlich SU, Yurcheshen M, Wittlin SD, Sellix MT. Chronomedicine and type 2 diabetes: shining some light on melatonin. Diabetologia. 2017;60(5):808-822.
- Bi H, Gan Y, Yang C, et al. Breakfast skipping and the risk of type 2 diabetes: a meta-analysis of observational studies. Public Health Nutr. 2015;18(16):3013-3019.
- Ofori-Asenso R, Owen AJ, Liew D. Skipping breakfast and the risk of cardiovascular disease and death: a systematic review of prospective cohort studies in primary prevention settings. J Cardiovasc Dev Dis. 2019;6(3):30.
- Bian L, Markman EM. Why do we eat cereal but not lamb chops at breakfast? Investigating Americans’ beliefs about breakfast foods. Appetite. 2020;144:104458.