Circadian rhythm and caffeine supplementation go hand in hand in many sports. Genetic profiling comes in handy when determining if you are a morning person capable of metabolizing a nice cup of coffee or your performance is better in the evening. New technology advances such as DNA testing of specific gene encodings and recent emerging literature suggest a noticeable relation between peak time and caffeine metabolism. 

Are you a morning person or a night owl? 

Circadian clocks that comprise clock genes are located in various tissues throughout our body. These circadian clocks regulate our daily physiological events such as hormone synthesis and release and metabolic processes. Our central clock, the pineal gland, is regulated by the light/dark cycles.

Central clock in the suprachiasmatic nucleus (SCN):

• Sleep/wake cycles.
• Controls the autonomic nervous system.
• Modulates the core body temperature.
• Regulates melatonin secretion.

On the other hand, feeding and fasting cycles are the ones that control our peripheral clocks. 

Peripheral clocks:

• Dominate local physiological processes.
• Promote glucose and lipid homeostasis.
• Regulates hormone secretion.
• Modulates immune respose.
• Manages the digestive system.

Core clock genes orchestrate, via a feedback loop, the circadian rhythm throughout our body. One of the primary core clock genes is CLOCK, which has a tight association with the energy metabolism status in various mechanisms.

CLOCK: circadian locomotor output cycles kaput is a clock protein. It is an essential element in the control and modulation of the circadian rhythm. In addition, CLOCK has a strong involvement with metabolic regulation.

Studies show that the NAD(H)/NADP(H)ratio depends on the binding capacity of CLOCK/NPAS2:BMAL1 transcription factors to DNA. In turn, there are several mechanisms dependent on this NAD interaction with circadian rhythm. Indeed, the downstream CLOCK-dependent reactions start with Napt, an encoding gene for restriction enzymes that control NAD+ concentration. Furthermore, NAD+ regulates deacetylase Sirt1, which governs the chromatin remodeling, mediated by CLOCK. Studies show that the disruption of NAD+ oscillation is linked to alteration in the circadian metabolic rhythm in mice.

Nutrients, Clock Genes, and Chrononutrition

Is it the time of day limiting your athletic performance?

It is essential to consider that the coding gene CLOCK 3111 is an element involved in regulating the central clock function. Therefore, in a sports context, it may serve as a marker of morning endurance performance. Another aspect to consider is that this gene has a close interaction with body temperature, melatonin release, and lipid utilization. Specific single nucleotide polymorphisms (SNP) in this gene show that C allele carriers have reported feeling fatigued in the morning and prefer having evening activities.

Another encoding gene with great application in the athletic and circadian rhythm context is CYP1A2. This codes for the enzymes that metabolize caffeine. In sports, such as racing, the supplementation of caffeine has been shown to improve performance. However, specific SNPs are associated with better caffeine metabolism. Those individuals carrying the C allele genotype have shown poor ability to metabolize caffeine, increasing their chances of developing heart disease. On the other hand, A allele genotypes metabolize caffeine at a fast rate. In this case, caffeine supplementation 30 min to 1 hour before activity can improve athletic performance in sports like sprint races.

The main objective of gene profiling is to improve athletic results by detecting genetic limitations or enhancing beneficial SNPs. The CLOCK 3111and CYP12A genes have a powerful effect on metabolism and circadian rhythm. Nevertheless, their application on athletic endurance shows that the body can be easily modified with supplementation, in this case, caffeine. – Ana Paola Rodríguez Arciniega, MS

References:

Mikulska, Aniceta Ada et al. “Assessment of Selected Clock Proteins (CLOCK and CRY1) and Their Relationship with Biochemical, Anthropometric, and Lifestyle Parameters in Hypertensive Patients.” Biomolecules vol. 11,4 517. 30 Mar. 2021, doi:10.3390/biom11040517

Oike, Hideaki et al. “Nutrients, Clock Genes, and Chrononutrition.” Current nutrition reports vol. 3,3 204-212. 27 Apr. 2014, doi:10.1007/s13668-014-0082-6

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