Meal Timing and Composition Affects the Circadian Clock

The future of medicine is looking at the timing of nutrients, meals, and circadian rhythms that help or hinder the body’s natural metabolic rhythm. Circadian rhythm disruption has been linked to obesity, insulin resistance, cardiovascular disease, and metabolic syndrome. A remarkable review study details groundbreaking information on how nutrient metabolism and the circadian clock are interdependent. This increasing body of information is at the forefront of metabolic research. Scientists believe that it is indeed the future of medicine. The timing of food and nutrient intake must be in sync with the body for the greatest benefit.
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The journal, Molecular Metabolism published a study, “Interdependence of nutrient metabolism and the circadian clock system: Importance for metabolic health” in March 2016. This article focuses on results of several studies that suggest that “nutrients provide an opportunity to restore or, alternatively, can destroy synchrony between peripheral clocks (in the body) and the central pacemaker in the brain as well as between peripheral clocks themselves”. Here are some of the study’s findings.

Meal Timing Helps or Hurts Internal Clocks and Metabolism

The natural light-dark cycle is the most potent driving force for the overall circadian rhythm but our internal, peripheral clocks rely heavily upon food intake cues. The brain’s central or master clock, the SCN found in the hypothalamus, depends on the natural light-dark cycle to set the timing of the body and talks to the body clocks found in our organs, cells, and peripheral tissue.
These clocks depend on nutrient input to determine the timing in addition to the master clock’s rhythm. Researchers have found that the timing of intake of food and nutrients can either help or hinder the peripheral clocks. Food intake at the wrong time of the day can disrupt the synchronization with the body’s central clock in the brain and compete against other peripheral clocks.
Eating at the wrong time of the day according the body’s circadian rhythm essentially puts a monkey wrench in metabolism. Researchers have found that when this monkey wrench occurs, it changes genes that control processes with mitochondria function, carbohydrate use and metabolism, lipid/cholesterol function, synthesis, and breakdown, protein function, and adipocyte or fat cell function. It even changes how the liver detoxifies toxins, the Kreb’s cycle with energy production, electrolytes and kidney function, and skeletal muscle use and storage of blood sugar.
One area of highlight focused on those who ate breakfast and those who didn’t. In this case, the researchers looked at young men who habitually followed one or the other pattern. Those men who routinely skipped breakfast had an increase in both LDL cholesterol and triglycerides, whereas those who ate breakfast in the morning had healthy LDL and triglyceride levels. In either case, the behavior either favorably turned on the genes and the peripheral clocks or it stressed them. In this study, eating breakfast set a healthy tone for LDL and triglyceride metabolism.
The research showed that when there was a consistent rhythm to eating and sleeping patterns within the context of the natural light-dark circadian cycle, there was a healthy oscillation or vibration to the clock and metabolism, i.e. the natural metabolic ebb and flow was turned on. They found in particular that three meals per day and possibly one snack in conjunction with the natural light-dark cycle were the most favorable. Patterns outside of this, like skipping meals, grazing, shift-work or extended travel and time zone changes, created the most distress to the clock genes.
Dietary Composition Helps or Hurts Internal Clocks and Metabolism

Dietary composition, i.e. the types of foods we consume also changes our circadian clocks. Scientists compared the Western Diet and the Mediterranean Diet and its effects on the body’s clocks. Both diets influenced the body clocks. Consumption of the Western Diet, composed of high saturated fat and high carbohydrate/sugar content, was found to negatively impact several of the gene clocks disrupting the internal rhythms.
High carb diets were shown to have controlling, disruptive influences on the clocks. The high carb intake was found to force clocks to accelerate and become out of sync. The rhythmic disruptions caused a cascade of cellular, gene, protein, enzymatic, and metabolic challenges that led to insulin resistance, disturbed leptin and adiponectin function, and obesity. Complex carbohydrates with high fiber were shown to be less likely to induce negative changes to the internal body clocks.
Think of what you feel like if you have a high carbohydrate breakfast, i.e. instant oatmeal, banana, and orange juice. The carb-rich foods create the immediate spike in blood sugar and then a crash. This metabolic challenge puts big monkey wrench in the body clocks. Not only are blood sugar levels wildly fluctuating with the pancreas, liver, and cellular metabolism working very hard, but the energy crash that often occurs after high sugar intake reflects the out-of-sync internal clocks and loss of metabolic energy.
Mediterranean Diet and Polyphenols Naturally Modulate the Peripheral Clocks

On the other hand, the Mediterranean Diet was found to help the natural vibration and rhythm of the peripheral cocks, helping the peripheral clocks and gene signals function well. The foods that comprise the Mediterranean diet are rich in vitamin A, polyphenols like resveratrol, proathocyanidins (grape seed extract), phytosterols, (seeds and nuts, e.g. pine nut oil) mono- and polyunsaturated fatty acids, and polyamines (wheat germ, rice bran, black rice, salmon, green peppers, etc).
These are key elements found to protect and naturally modulate the peripheral clocks, especially when out of sync with timing or struggling with metabolic problems and obesity. This method of eating emphasizes consuming a wide variety of vegetables, fruits, legumes, seeds, nuts, whole grains, olive oil, fish, poultry, herbs, spices, and moderate red wine intake. Red meat intake occurs a few times per month, processed foods and sweets are generally avoided.
Polyphenols were most notably favored. These plant-based compounds are found in richly colored fruits and vegetables and have a known direct effect on the peripheral, molecular clocks. They have been shown to actually modulate the clocks in a helpful manner, i.e. able to move the clocks faster or slower to get back in balance with the central clock. Resveratrol and proanthocyanidins like grape seed extract have the capacity to modulate peripheral body clocks in both healthy and obese individuals. Red and white wine, dark chocolate, grapes, blueberries, peanuts, cranberries, bilberries, contain resveratrol and proanthocyanidins. These compounds were shown to benefit circadian rhythm even when consumed with a high fat, high carb/sugar diet. Grape seed extract specifically helped to normalize the clocks in the liver and gut.
Turning on Key Regulatory Compounds

Two key regulatory compounds were highlighted in addition to diet and timing. These regulatory compounds are AMPK and SIRT1. AMPK and SIRT1 are key regulatory agents, like a master switch that the body uses for keeping the nutrients/meals, energy and body clocks in sync. There are several ways to help these regulatory compounds wake up to do their job. Exercise, fasting/not over-eating, and resveratrol are critical triggers for turning on AMPK and SIRT1. Known compounds that support AMPK function are acetyl-l-carnitine, curcumin, quercetin, green tea extract, lycopene, ginger, and cruciferous vegetables.
The Molecular Glue between the Endocrine System and Body Clocks

In addition to the regulatory nutrients, diet composition, and meal timing, there was a significant focus on receptor sites. Researchers have found that the “molecular glue” that connects circadian rhythms with metabolism depends on nuclear receptors. These receptors connect the endocrine system to the body clocks. There are both natural and synthetic receptors. Natural receptors include the omega-3 oils DHA, EPA, vitamin A and its derivatives, cholesterol, thyroid hormone, myristic acid (found in cheese, butter, coconut oil, palm oil, and very small amounts in dairy, eggs, meat, seafood), oleic acid (olive, avocados), and linoleic acid (grass fed meats and dairy).
The profound circadian clock discoveries go against the popular misconception that multiple small meals per day are essential for healthy blood sugar, leptin, and metabolism. Certainly this growing body of evidence on circadian rhythms and its impact on metabolism and hormones provides staunch evidence that this mentality and recipe for disrupted health needs to shift.
Government Subsidized Foods Not Helping

An original investigative report published August 2016 by Journal of the American Medical Association (JAMA) Internal Medicine found that the US government federal subsidized crops (corn, soybeans, wheat, rice, sorghum, milk, and meat) are literally fueling the obesity crisis and heart disease epidemic. This may not come as a surprise to many, but the evidence published shows that these seven foods are very common in the American diet and comprise much of the calorie intake. The program was once meant to help struggling small family farms has now become the focus of the American diet providing cheap, high calorie, nutrient poor foods. This Western Diet adds to the burgeoning burden of obesity and metabolic syndrome going against the grain of what is needed for body clocks and healthy metabolism.
The recipe of disrupted body clocks and poor metabolism fits in with the pattern of what has been happening over the previous few decades. The late twentieth century to the present has brought a rising metabolic conundrum felt throughout the world with the obesity and diabetes epidemic. The FDA has not helped with obesity epidemic. High carb, grain based diets, low/no fat diets, skipping meals, grazing, and sleep deprivation associated with high artificial light at night exposure set the tone for disrupted rhythms which have created a perfect storm of heart disease, diabetes, obesity, and high inflammation.
One of the summary statements of the article provided this glimpse into the future. “Considering that metabolic disease is associated with circadian disruption in humans and that the clock uses nutrient input to set the local time (peripheral clocks), it is conceivable that both the timing and nutrient composition of one’s diet might be key components of personalized medicine’s future, in parallel to behavioral and genetic predisposition.” We can, however, use this information immediately.
To paraphrase Byron Richards, CCN, “If you eat like the (food) pyramid, you will look like the pyramid.” If your light-dark master clock and peripheral clocks cued heavily by food is also off and the Western Diet is at the core of your meals, you will undoubtedly be one of millions in this country struggling to maintain health. Focus on getting your body more in-tuned with the natural light-dark rhythms. Follow The Leptin Diet by eating three meals per day rich in quality, diverse foods loaded with the omega-3 oils, cruciferous vegetables, resveratrol, grape seed extract, olive, coconut, and palm oils.
To optimize and support the diet, consider supplementation with resveratrol, grape seed extract, acetyl-l-carnitine, curcumin, quercetin, green tea extract, lycopene, and ginger. Take this information and think back to your relatives a generation or two before you. Their lives followed these basic patterns of three meals per day and early to bed and early to rise. Often there are stories of family members living to 90 or 100 years of age, no medications, no surgeries, and remarkable health. What happened?
Nutritional Options

DHA/EPA – Omega-3 oils are fundamental to receptor site function, which are the molecular glue that keeps the endocrine system in sync with the clocks. Fish oil provides support for blood sugar, leptin, thyroid, and inflammation management. DHA and EPA are essential oils. They must obtained daily from the diet or supplementation.
Resveratrol – This powerful anti-aging antioxidant is often considered the fountain of youth. Resveratrol has been found to naturally support body clock rhythms and may be a dominant compound literally turning the body clocks of time. It helps support leptin, SIRT1, AMPK, cholesterol, and blood sugar function.
Green Tea Extract – In addition to its well-known antioxidant effects, green tea extract supports the activation of the master enzyme switch, AMPK, needed to burn fat and sugar for fuel. It works synergistically with resveratrol and grape seed extract. Green tea extract helps support healthy blood sugar, fat burning, and cholesterol metabolism.
Acetyl-L-Carnitine (ALC) – This amino acid is known for its supportive role in making the memory neurotransmitter. ALC plays additional roles in chemistry as it is able to turn on regulatory compounds SIRT1 and AMPK. Many metabolic and mitochondrial disorders benefit with extra ALC as it supports the burning of blood sugar and fats for energy production.
Vitamin A/ Beta Carotene – The Mediterranean Diet is rich in vitamin A and the carotenoid family. Vitamin A is essential for not only eye health, but helps the skin and brain with clock rhythms and oxidative stress. People often shy away from vitamin A, but it is an essential nutrient. Your body will convert beta carotene into vitamin A as needed, making beta carotene a safe supplementation option.
Grape Seed Extract – This potent bioflavonoid from the polyphenol family is widely known for collagen, antioxidant, immune, and heart health support. Researchers identified grape seed extract as a powerful modulator for body clocks even with high fat and high carb diets.


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