Tick tock: Meal timing and chronobiotics supplementation could play crucial role in combatting obesity and cardiometabolic diseases

Chrononutrition is an emerging field of nutrition science research, which suggests that consuming specific nutrients at different times of the day could positively impact cardiometabolic health and weight management, said Dr Darel Toh, scientist at Singapore Institute of Food and Biotechnology Innovation (SIFBI). 

It refers to the study of how the timing of food intake may affect health. As circadian rhythms are known to influence various body functions, including digestion, hunger and metabolism, chrononutrition investigates the interactions between meal timings, diet, and the body clock.

“One commonality across ‘healthy diet models’ recommended by authorities worldwide is that ​attention is mainly paid to the quantity, types, and quality of foods. Often lacking is the aspect of when we should eat our meals.​

“Timing of food consumption is an important determinant in diet-disease associations, and appropriate intake timing of specific foods or nutrients should be considered in daily dietary planning. Existing human clinical trials data are limited, but there has been an exponential growth in interest as well as opportunities in chrononutrition,” ​Dr Toh said at our Growth Asia Summit 2023.

According to Dr Toh, light plays a major role in the maintenance of circadian rhythmicity and modulation of the body’s central clock.

In addition, peripheral clocks that reside in various tissues throughout the body are also regulated by light exposure and affected by external factors, including timing of meals, wake up time, and physical activities.

“For example, individuals who have a large breakfast and early bedtime often have good synchronisation between their central and peripheral clocks. The reverse is true for individuals who tend to have heavy dinners and sleep late or even during the day, which may have adverse effects on cardiometabolic health, such as insulin secretion and hepatic gluconeogenesis.”​

In a trial involving more than 3,000 overweight and obese adults, the participants underwent a standardised weight loss programme for 19 weeks. They were categorised into two groups — individuals who consumed a majority of calories early in the day and those who did so later in the day.

Even at baseline, participants who ate later had higher indices of body fat, BMI and triglyceride levels, as well as increased risk of cardiometabolic conditions like insulin resistance.

At the end of the study, it was found that the weight loss rate was significantly greater among early eaters than late eaters.

Furthermore, there have been a number of systematic reviews that analysed the impact of skipping breakfast. Results showed that there is a “clear increase” in the odds of overweight and obesity, cardiovascular diseases, and all-cause mortality risk for people who skip breakfast.

In some studies, comparisons were made between a high-energy breakfast with a low-energy dinner versus a low-energy breakfast with a high-energy dinner.

“Specifically for high-energy dinners, glucose levels tend to be a lot less regulated, as big spikes in glucose levels were observed. Therefore, simply shifting the time that we have meals — from 9pm to 6pm, for instance — may have an influence on glucose metabolism.​

“This goes beyond glucose management. In the area of appetite regulation, late eaters are often associated with greater subjective hunger and poor profiles of related hormones, which may, to some extent, increase the propensity to greater energy intake,” ​Dr Toh shared. 

Ideal timing​

“Increasing literature suggests that chrononutrition is not just about when we eat our meals, but what exactly we eat during these meals — for instance, when is the best time to eat carbohydrates, proteins, fats, and other micronutrients?”​

In Singapore, SIFBI collaborated with Nestle to examine two common types of rice that are eaten locally — low-GI basmati rice and high-GI glutinous rice. Participants in the study consumed them at two different times of the day.

Notably, the findings showed that regardless of GI value, the meals consumed during breakfast consistently showed a lower glucose response than meals consumed during dinner. Between morning and evening meals, there were also clear differences in the plasma metabolome.

In a separate study, participants were given green tea with a high-carbohydrate meal. A positive effect in glucose modulation was observed only when green tea was paired with the meal in the evening.

“When it comes to micronutrient-dense foods, certain bioactive compounds may potentially elicit greater health effects when consumed later in the day, but this will need to be substantiated by more evidence.”​

On the other hand, a recent paper suggested that foods with high fat content are “ideally consumed earlier in the day” due to the differences in absorption and bioavailability of fats consumed at different times of the day.

For proteins, higher dinner protein was associated with greater insulin resistance, while higher breakfast protein improved cardiometabolic risk factors, such as higher HDL (“good” cholesterol) and lower blood pressure. This indicates a need for even distribution of protein throughout the day.

“It seems that different proteins have different effects on the circadian rhythm. And this may be modulated by amino acid profile and protein quality. Moreover, published research from last year indicated that certain amino acids, particularly serine, may have a positive influence in the expression of various clock genes.”​

Dietary chronobiotics​

The modern lifestyle is often accompanied by shift work, breakfast skipping, and heavy dinners, which can cause misalignment between the central and peripheral clocks.

Clock gene expression has also been linked to the gastrointestinal microbiome, as well as metabolites produced by the gut.

Dietary chronobiotics are “agents capable of influencing biologic rhythm parameters”.

“Supplementation of certain ​dietary compounds, such as chronobiotics, polyphenols and prebiotics (inulin and beta-glucans), to directly modulate and improve circadian rhythmicity — ​when it is compromised due to late food intake and other lifestyle habits — could help realign some of these synchronies,” ​explained Dr Toh.

Some novel chronobiotic compounds include epigallocatechin gallate (EGCG), nobiletin, piceattanol, resveratrol, and ursolic acid.

For example, in vitro studies have shown that pre-treatment with resveratrol, mostly found in red grapes and grape-derived products, could improve circadian rhythmicity of clock genes in HepG2 cells exposed to free fatty acids-induced metabolic disorder.

“Having said that, scientific evidence remain very limited today. The application of chronobiotics in circadian restoration and alleviating increased health risks associated with late night eating is promising, and needs to further explored,”​ he concluded.