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A Mediterranean diet eaten earlier during the day with limited calories can have health benefits: Improved blood pressure, improved levels of cholesterol, glucose, insulin and, better muscle build and recovery, improved quality of sleep, lower risk of chronic diseases, and a healthier body weight.
Introduction
We can buy food anytime anywhere, and we can work anytime anywhere. Eating times are no longer reserved for three meals a day, and working times are not reserved for 9 to 5 anymore. Although it is human nature to eat and be active during the day, and to fast and rest in the evening and during the night, eating and working in the evening and night has become normalized, although research shows this increases the risk for metabolic diseases such as diabetes type 2, obesity and depression. To lower these risks and also to lose weight, Intermittent Fasting has become a popular diet over the last years (Are you on a Fad diet?). Many people consider Intermittent Fasting a more doable way to lose weight than a continuous calorie- restricted diet, although in the long run Intermittent Fasting does not seem to be more effective.
In this article we describe the scientific evidence on the effects of Intermittent Fasting on weight loss and health.
What is Intermittent Fasting?
Intermittent Fasting is an umbrella term for eating regimes that involve periodic fasting. The basic idea is that the body needs periods of fasting for repair, maintenance and preservation of body cells, and that periods of eating are necessary for cell growth and reproduction.
There are different forms of Intermittent Fasting, which also seem to have different effects on weight loss and on health. We discuss three forms of Intermittent Fasting, with a special focus on Early Time- restricted Eating because of its positive effects.
What does science say?
Scientific research on the effects of Intermittent Fasting on humans is scarce, and more limited than research results from animal studies among rodents. One explanation is that human studies of fasting can be ethically difficult. After all, humans can hardly be confined for extended periods and exposed to a particular fasting regime under controlled conditions, as in animal studies. In studies that rely on self-reporting, where people follow a particular fasting diet in their homesetting, data reliability and compliance (to what extent does someone actually adhere to the diet?) are complicating factors.
Research on Intermittent Fasting among rodents shows convincing positive health effects including improvement of metabolic parameters such as glucose, insulin and cholesterol; improvement of cognitive and learning abilities; and activation of antioxidants that protect against cellular stress.
Although rodents and humans have similarities, the research results among rodents cannot simply be generalized to humans. One reason is that the effects of Intermittent Fasting proceed through the influence of fasting on various body processes including on the biological clock. Rodents and humans have opposite biological clocks: by nature rodents eat and live at night, while in humans it is during the day.
Studies of Intermittent Fasting among humans show mixed results, and are mainly executed among people with obesity and metabolic syndrome. Some studies report weightloss and improvements in metabolic parameters such as glucose, insulin, leptin, cholesterol, blood pressure and inflammation levels. Other studies report no weight loss and negative effects such as electrolyte imbalance and muscle loss. However, positive effects do seem to be expected with Early Time- restricted Eating, about which more later.
Three Forms of Intermittent Fasting
In this article, we discuss three common forms of Intermittent Fasting:
1. Alternate-day fasting
This involves alternating fasting days during which no calories are consumed via food or beverages, and eating days during which foods and beverages are consumed ad libidum.
Research among overweight/obese and non-obese people shows that this form of Intermittent Fasting can result in some weight loss, especially because people cannot meet the intended caloric intake on eating days. They seem to be less hungry, although adherence to this form of Intermittent Fasting seems very challenging in the long run. There seems no difference in weight loss between alternate- day fasting versus a continuous calorie restricted diet.
Although the effects of alternate- day fasting on metabolic parameters such as glucose, insulin, cholesterol and inflammation are inconclusive, there seems to be a difference compared to the metabolic parameters with a continuous calorie restricted diet:
The calorie restriction in continuous fasting appears to have metabolic benefits while in alternate-day fasting metabolic disadvantages may occur. A possible explanation is that a lot has to be consumed on eating days and although this often does not fully succeed (leading to weight loss), it appears that this “overeating” can still result in less favorable metabolic parameters such as blood pressure, lipids, glucose and insulin. When alternate-day fasting is combined with calorie restriction, metabolic benefits do seem to occur.
-> Catch-up days involving high consumption (overeating- days) appear to be unfavorable for health. Calorie restriction appears to provide metabolic benefits.
2. Modified fasting regime (5:2)
This involves a 20- 25% calorie restriction on regularly scheduled fasting days, and eating days during which foods and beverages are consumed ad libidum. Often this is a regime of 2 non-consecutive fasting days and 5 days of eating without restriction.
Research among overweight/obese people shows that this form of Intermittent Fasting can result in weight loss comparable to the weight loss with a continuous calorie restricted diet. The effects on metabolic parameters such as glucose, insulin, cholesterol and inflammation are inconclusive and also do not seem to differ from a continuous calorie restricted diet.
3. Time-restricted eating: Early and Late
This form of Intermittent Fasting involves eating and drinking during a certain timeframe, and not outside of it. This form has several variants such as Early Time- restricted Eating which involves fasting later in the day and at night; and Late Time- restricted Eating which involves skipping breakfast and eating later in the day.
- Advantages of Early Time- restricted Eating
Research among people without obesity shows that night time fasting of more than 11 hours leads to weight loss. Furthermore, it appears that consuming most of the calories earlier in the day is associated with lower body weight and improved health in terms of improvement on metabolic parameters.
Even if the same amount of calories is eaten and there is no weight loss, Early Time-restricted Eating with 18 hours of fasting results in more metabolic benefits such as improved insulin sensitivity, blood pressure and oxidative stress, compared to an eating regimen of three meals a day with 12 hours of fasting. It is expected that additional weight loss via calorie restriction would lead to even more metabolic benefits. Furthermore, in the longer term Early Time- restricted Eating seems to lead to more weight loss compared to a continuous calorie restricted diet with identical diet quality, meal frequency and eating behavior.
-> There is evidence that eating earlier in the day and prolonging the nightly fasting interval reduces the risk of common chronic diseases, even when calories are not restricted and there is no weight loss. Additionally restricting calories, is expected to lead to additional health benefits.
- Disadvantages of Late Time- restricted Eating
Eating late during the day or at night, as by people on night shifts, is associated with a higher risk of obesity, diabetes, cardiovascular disease and cancer. Late Time-restricted Eating seems to have no or only negative effects on metabolic parameters such as glucose, lipids and blood pressure.
Three mechanisms of Intermittent Fasting
Intermittent Fasting is believed to affect metabolic parameters via the influence of fasting on: 1) the biological clock; 2) gut microbiome; and 3) lifestyle behavior.
1. Biological clock
Humans and animals have biological clocks (circadian rhythms) which control many bodily functions and processes on a, slightly over, 24-hour cycle. This includes the sleep-wake cycle, blood pressure, heart beat, body temperature and hormonal production/ secretion.
The master clock is located in the suprachiasmatic nucleus (SCN) of the hypothalamus, whereas peripheral clocks are distributed in a number of cells throughout the body such as in organs and in fat and muscle cells. These peripheral clocks are regulated by the masterclock. The SCN is both autonomous and entrained by external time cues.
Daylight and eating/fasting are the main cues (zeitgebers) for the operation of circadian rhythms. Desynchronization of the biological clocks increases the risk of chronic diseases. Consuming energy and being active outside the normal eating/ working (- out) phase , for example late at night can disrupt the biological clocks and thus disturb the energy balance. For example, working in night shifts leads to disruption of circadian rhythms, and is associated with increased risk of chronic disease. (Sleep and health).
Circadian rhythms have an impact on metabolism across the day. For example, insulin sensitivity decreases throughout the day and into the night. Meals consumed at night are associated with greater glucose and insulin exposure after eating, compared to the same meals eaten earlier during the day. This leads to an increased risk of type 2 diabetes.
The influence of Intermittent Fasting on circadian rhythms can lead to changes in the level and frequency of hormone secretion. This includes insulin, cortisol, thyroid hormones, growth hormone, estradiol, melatonin and serotonin. For example, there is evidence that periodic fasting can lead to electrolyte imbalances; increased insulin sensitivity, decreased thyroid hormone levels (slower metabolism) and increased cortisol levels (linked to muscle loss).
Intermittent Fasting that includes reduced calorie intake in the evening and no intake at night synchronizes food ingestion with optimal hormonal response after the intake of food. This includes having the largest meal earlier in the day and fewer carbohydrates later in the day. Although the difference between being a morning type or an evening type also seems relevant (Timing is everything in nutrition)
-> It seems that if the intake of food is aligned with the circadian rhythm of day and night, this leads to health benefits such as improved blood pressure, cholesterol levels, glucose and insulin levels, lipid levels, better muscle build and recovery; improved quality of sleep; less risk of chronic diseases; and better body weight regulation.
Contrary to what is sometimes thought, there is evidence that Early Time- restricted Eating combined with exercise in the evening has more positive effects on metabolic parameters such as insulin and cholesterol, and on VO2 max, than exercise in the morning. It also seems that exercising aligned with circadian rhythm is relevant for achieving intended training results such as muscle growth (Timing is everything in exercise).
2. Gut microbiome (Mediterranean diet)
The functioning of the gastrointestinal tract is closely linked to circadian rhythm. For example, gastric emptying and blood flow are greater during the day than during the night. Desynchronized circadian rhythm, for example due to lack of sleep or working in night shifts, seems to affect gastrointestinal tract as well as gut microbiome.
Gut microbiome affects physical and mental health (Your poop tells it all). It seems Intermittent Fasting can have a positive effect on the diversity of the gut microbiome. Gut microbiome diversity is relevant to metabolic parameters and chronic disease risk. Also, the quality of food is relevant. The Mediterranean diet seems to be the most beneficial for health.
The Mediterranean diet prescribes whole grains, legumes, fruits, vegetables, olive oil, fish, and nuts with a moderate allowance of alcohol, dairy products, and meat. Traditionally, this diet derives its most calories from fish and plant-based foods, with 30% of total calories from unsaturated fat, 50% carbs and 20% protein.
Mediterranean diet is the most extensively studied diet to date. Research shows this diet is nutritionally adequate for the general public and may have the potential of preventing micronutrient deficiencies. It has preventive and therapeutic potential for many chronic diseases like non-alcoholic fatty live disease, cardio vascular disease, metabolic syndrome, colorectal and breast cancer, decreased risk of type 2 diabetes.
There is no evidence of adverse effects associated with the Mediterranean diet. The diet has preventive and therapeutic potential for many chronic diseases; is highly suitable for the general public for the prevention of micronutrient deficiencies and specifically for patients who are more health-conscious than just weight loss oriented. The Mediterranean diet is a low- inflammatory diet linked to improved power and muscle endurance and body composition.
3. Lifestyle behavior
Intermittent Fasting seems to influence lifestyle behavior in several ways, among which:
- Lower calorie intake on eating days
In most forms of Intermittent Fasting the time frame of eating is limited, which limits the overall caloric intake. Alternate-day fasting and modified alternate- day fasting seems accompanied by a lower overall energy consumption: A 1-day fast seems to reduce caloric intake on the subsequent 3 eating days with 10%. Skipping breakfast does not seem to increase food intake during lunch. It also does not seem to increase after- lunch appetite, although this is a common obesity- related belief, and can still be the case in some individuals.
- Timing of food seems most relevant for total caloric intake and food choice.
The timing of food intake aligned with the circadian rhythm (dark- light cycle) such as with Early Time- restricted Eating, seems to have an important impact on food intake, energy efficiency and weight control. Shift- en night workers who eat late at night have alternations in appetite- regulating hormones that may lead to an increased energy intake and cravings for unhealthy foods (Sleep and health).
- Better sleep and more energy
It seems that increasing nightly fasting duration to over 14 hours, can lead to improved self-reported quality of sleep, and improved energy levels. Night time eating is associated with reduced sleep duration and poor sleep quality, which can lead to insulin resistance and increased risks of obesity, diabetes, cardiovascular disease, and cancer. Eating at abnormal circadian times such as late at night, seems to desynchronize circadian rhythm and as a result, disrupts sleep patterns and affects energy levels.
Concluding
It is not just about eating less calories, the timing and quality of the diet are also important:
-> Overeating days are unfavorable for health
-> Calorie restriction provides health benefits
-> Eating earlier in the day and prolonging the nightly fast reduces health risks
-> When food intake is aligned with circadian rhythm, health benefits are expected.
-> The Mediterranean diet seems best
What else?
Intermittent fasting can be be a godsend and provide a structure to curb unhealthy behaviors. But it may not be appropriate for everyone. For example, it can also lead to a fixation on food, a tendency to overeat, or restrictive negative associations with health behavior.
Whatever method a person chooses to lose weight, because that is one of the main reasons for people to do Intermittent Fasting, it is important to continuously monitor body weight and food intake, if they want to maintain their new weight.
Losing weight leads to a decrease in resting metabolism largely because muscle mass is lost in addition to fat mass. Some 5-10% weight loss results in the body permanently requiring 100kcal less per day, regardless of whether this weight loss is the result of a crash diet or a gradual approach. This requires permanently eating less and exercising more to maintain muscle mass (You need more strength training than you think). For many people, this might feel like an ungoing battle.
There is growing evidence that a form of fasting has health benefits. When the focus is placed on the benefits; when effort is being put to minimize the perception of fasting as a restriction; and when more attention is paid to the quality of nutrition, rather than on losing weight alone, Intermittent Fasting might act as a flywheel to other positive health behaviors as well.
References
Berk, Dr. Kirsten A.C. (2024). Intermitterend Vasten. Online webinar via: Vereniging Arts en Leefstijl
Kim BH, Joo Y, Kim MS, Choe HK, Tong Q, Kwon O. Effects of Intermittent Fasting on the Circulating Levels and Circadian Rhythms of Hormones. Endocrinol Metab. 2021;36(4):745-756.
Patterson RE, Sears DD. Metabolic effectsof intermittent fasting. Annu Rev Nutr 2017;37:371–93.
