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What we eat, as well as when we eat, can have a profound effect on our daily circadian rhythms. “Chrono-nutrition” is a term that refers to the delicate interplay between the diet and our internal clock system.

Daily circadian rhythms are governed by our master clock in the hypothalamic suprachiasmatic nucleus (SCN). These rhythms influence many bodily processes, including detoxification, metabolism, insulin secretion, fatty acid uptake, core body temperature regulation, and melatonin and cortisol secretion. Light/dark cycles and food intake serve as zeitgebers, or environmental cues, that impact circadian rhythms. While light and darkness primarily affect the master clock, eating and fasting affect peripheral clocks in organs and other tissues, such as the liver, gut, and adipose tissue.

Master and peripheral clocks are synchronized, although living outside the body’s natural rhythms can cause these two systems to become disjointed. Factors such as altered sleep patterns, artificial light, a high-fat diet, chronic stress, a sedentary lifestyle, and shift work can all negatively affect our diurnal rhythms. Disruptions to our clock systems have been implicated in several health conditions, including metabolic syndrome, obesity, and cardiovascular disease.

This blog will review some nutritional influences on circadian rhythms, including the role of the gut microbiome and the application of time-restricted eating.

The Gut Microbiome

Digestive function and the gut microbiome are closely connected to our circadian rhythms. The composition of the gut microbiome fluctuates throughout the day due to the feeding/fasting cycle and the impact of diet on digestion. Food intake affects daily motility, enzymatic activity, and epithelial cell turnover. Only particular microorganisms exhibit diurnal rhythms, and diet dictates the diversity of these oscillators. A plant-based diet supports the growth of bacterial species that are influenced by circadian rhythms, while a high-fat diet negatively impacts variety.

The gut microbiota also exerts effects on circadian rhythms. Based on diet composition, specific microbes create metabolites that influence clock gene expression in the liver. Researchers looked at the impact of a low-fat or high-fat diet on control mice, specific-pathogen-free mice, and germ-free mice. Germ-free mice gained significantly less weight regardless of diet. A high-fat diet influenced the expression of clock genes bmal1 and clock in the specific-pathogen-free mice while also significantly reducing the alpha-diversity of the microbiome. This effect was not seen in the germ-free mice, which led researchers to conclude that particular microbes play a role in clock gene expression. Oscillating bacteria from this study were found to be from the Lachnospiraceae family, which produces the short-chain fatty acid butyrate. A plant-based, fiber-rich diet can help support the growth of these butyrate producers.

The Impact of Diet

Researchers are investigating how certain foods either support or disrupt the circadian rhythm. Caffeine and alcohol, as examples, affect peripheral clock systems. The consumption of sugar-sweetened beverages contributes to increased visceral adipose tissue, influencing the cortisol-awakening response (CAR). A study of adolescents with overweight or obesity found that those with a high intake of sugar-sweetened beverages had a 22% higher CAR compared to those with a low intake.

High-fat diets have been shown to negatively affect feeding and fasting cycles in rodent models. Mice that consumed a diet rich in both fat and salt experienced less locomotor or physical activity as well as disruptions in the oscillations of glucocorticoid secretions and clock gene expression in the adrenal glands. Tryptophan is a precursor to melatonin, a hormone that regulates diurnal rhythms and is influenced by blue light. Tryptophan depletion in mice led to lower physical activity, while a high-fat diet altered the rhythm of tryptophan metabolites in the liver and SCN. Avoiding high-fat diets and consuming adequate amounts of tryptophan can support proper melatonin production and sleep patterns.

Polyphenols affect both core and peripheral clock gene expression. For example, a rat study found that grape seed extract, a rich source of anthocyanins, was able to modulate the liver’s circadian rhythm. However, the effect on different clock genes was dependent on the time of day the extract was administered. A study of gray mouse lemurs demonstrated that resveratrol initiated sirtuin 1 (SIRT1) activity, lowered mean body temperature, and decreased physical activity. SIRT1 activates the circadian clock gene Bmal1. Finally, cacao procyanidins exerted time-dependent effects on the expression of clock genes in the liver of mice. It also increased glucagon-like peptide-1 (GLP-1) and insulin levels.

Lutein and Zeaxanthin

The SCN is influenced by light and dark cycles due to the monosynaptic pathway from the retina. The macula of the retina contains the carotenoids lutein, zeaxanthin, and meso-zeaxanthin, which exert protective effects against oxidative stress and damage caused by blue light. In addition to contributing to ocular inflammation, blue light from phones and computer screens can perturb circadian rhythms. The consumption of lutein and zeaxanthin, either through diet or supplementation, is a nutritional strategy to support the retina and internal clock system in the face of daily exposure to screens and artificial lights.

Retinal pigment epithelial (RPE) cells that were exposed to blue light experienced a significant decrease in proteasome activity (40-60%) and decreased expression of complement factor H (CFH) and monocyte chemoattractant protein-1 (MCP-1), which are involved in the inflammatory response. Inflammation was modulated when cells were treated with a lutein and zeaxanthin solution.

In a separate study, rhesus monkeys received lutein or zeaxanthin supplementation for 22 to 28 weeks, and their retinas were exposed to blue light. Half of the monkeys also had a low omega-3 fatty acid intake. Researchers found that lutein or zeaxanthin supplementation helped protect the fovea of the retina from the effects of blue light, while omega-3 fatty acids protected the parafovea.

Meal Timing and Time-Restricted Eating

Meal timing affects the bidirectional relationship between food and our circadian rhythms. Some essential bodily processes such as gastric emptying, thermogenesis, and insulin secretion are highest in the morning. This suggests that it may be best to have a greater intake of food at the beginning of the day compared to the evening. In addition, eating carbohydrates in the morning may be better for some individuals due to improved glucose tolerance.

The Bmal1 clock gene influences fat storage. Bmal1 deficient mice do not develop obesity or fatty liver while on a high-fat diet, and wild-type mice fed during their most active phase of the day (when Bmal1 expression is lowest) have less obesity compared to mice that were fed ad libitum. This supports the idea that eating high-fat foods late at night contributes more to weight gain compared to other times of the day.

Time-restricted eating (TRE) limits food consumption to a particular window during the day and has been studied as a strategy to support circadian rhythms. Since it does not restrict calories, this method can be less restrictive compared to other fasting protocols. In fact, a systematic review of 23 studies found an 80% adherence rate to time-restricted eating protocols. Time-restricted eating has been found to increase adipokine levels, which can contribute to fat loss and insulin sensitivity. It also helped modulate blood pressure in diabetic mice and restored disrupted blood pressure circadian rhythm. A study looking at the skeletal muscle of men with overweight or obesity found that time-restricted eating induces oscillations in amino acid and fatty acid transporter genes, while leaving core clock genes unaffected.

The time of day of the TRE window has an effect on health outcomes. Skipping breakfast, which coincides with a later eating window, has been shown to significantly reduce morning cortisol. On the other hand, an earlier eating window reduces evening cortisol while increasing morning cortisol. This encourages a more normal pattern of cortisol secretion throughout the day.

Men with prediabetes followed an early time-restricted eating protocol in which they ate within a 6-hour window with dinner before 3pm. Calories were maintained at a level such that weight remained steady. This protocol improved blood pressure, oxidative stress, insulin sensitivity, and beta cell responsiveness independent of weight loss. It also reduced the men’s desire to eat in the evenings. A separate study of early time-restricted eating also found that an earlier eating window decreased ghrelin levels and decreased the desire to eat by increasing the satiety hormone peptide YY.

Closing Thoughts

• While a high-fat diet, such as the Standard American Diet, negatively impacts circadian rhythms and the diversity of the gut microbiome, a diversified plant-forward diet helps support our internal clock system. Incorporate a variety of colorful plant foods rich in polyphenols and limit processed foods.
• Consume quality protein that contains tryptophan as a strategy to support proper melatonin synthesis. Sources of tryptophan include turkey, chicken, milk, oats, tuna, and bananas.
• Lutein and zeaxanthin protect the retina against oxidative stress. Lutein is found in foods such as green vegetables and corn, while zeaxanthin is in corn, leafy greens, and egg yolks. Supplementation may also be appropriate for some individuals.
• Time-restricted eating is a strategy that can support metabolism and reset feeding patterns. It may be most effective to eat within an earlier time window rather than consuming food late in the evening.
• Meal regularity has also been found to be important for metabolic processes. Be sure to consume meals at consistent times each day, even if you are eating within a shortened time window.

If you plan to make food, eating, or supplement changes, have food or supplement allergies, or have questions about which foods, supplements, or eating strategies are best suited for your health, talk to your doctor, nutritionist, dietician, or another member of your healthcare team for personal options based on your circumstances.