ESCUELA PROFESIONAL DE

NUTRICIÓN HUMANA

Crononutrición

Avances en nutrición clínica

MSc. Luis Baquerizo

 Regulación fisiológica circadiana

Metabolic Effects of Intermittent Fasting. Annual Review of Nutrition, 2017.

Mecanismo integrador del control del apetito
1729 – describió por
primera vez la
ritmicidad circadiana
Jeffrey C. Hall Michael Rosbash Michael W. Young
 Definiendo algunos conceptos
• Ritmo:

– Cambios fisiológicos recurrentes estadísticamente validados y con una curva reproducible.

– Se pueden identificar promedios, pico máximo y mínimo, amplitud y duración de las fases.
• Sincronizador:

– Marcador del tiempo, agente, activador.

– Pueden ser internos y externos, primarios o secundarios, dominante o modificable.
• Biorritmo:

– Ritmo en el cual permanece la periodicidad biológica en ausencia del sincronizador.

CHRONOBIOLOGY.
Annu Rev Physiol,
1969.
(2010). Garaulet, M., Ordovás, J. M., & Madrid, J. A. The chronobiology, etiology and
pathophysiology of obesity.
Genes reloj en la salud y
enfermedad

Circadian Locomotor Output Cycles Kaput

(CLOCK)

Brain And Muscle ARNT-Like 1 (BMAL1)

Period (PER1 and PER2)

Cryptochrome (CRY1 and CRY2)

Tips from the tip of the iceberg. Nature,

2008
Clock Gene Mutant mice Metabolic alterations Human genetic Metabolic alterations
in mutant mice variant in humans
Obesity, metabolic syndrome, higher
energy and fat intake, higher
Hyperphagic and obese, develop a CLOCK risk of developing diabetes and
Clock Δ19 metabolic syndrome
SNPS hypertension, alterations in the
autonomic nervous system

Suppressed diurnal variations in

Bmal1 -/- glucose and triglycerides and
BMAL2 High risk of developing type 2 diabetes
in obese patients
abolished gluconeogenesis rs7958822

Increased insulin secretion and lipid Increase in carbohydrate intake,

CRY1
CRYs Cry1/2 -/- storage in adipose tissue, elevation significant increase in insulin
of proinflammatory cytokines rs2287161 resistance

PER2 Abdominal obesity, several

PER2 Per2-/- Obesity when fed a high-fat diet
obesogenic behaviors
SNPs

Reduced spontaneous locomotor REV-ERBα Obesity resulting from decreased

REV- Rev-erbα-/- activity rs2314339 physical activity
ERBα
Since 2008: Clock variants and Obesity
 CLOCK 3111TC and Weight Loss

From more than 200 SNPs in ONTIME population

CR Period
MTNR1B APOA5 Y MCR4

Leptin FT
PPAR O APOA2 BMAL
Adiponectin
REVERB

ONTIME ClinicalTrials.gov Identifier: NCT02829619

CLOCK 3111TC and Weight Loss
Garaulet et al., International Journal of Obesity, 2009.
 Daily rhythms alterations were predictors
of weight loss difficulties
Wrist Temperature Activity

LOW
RESPONDERS

Low responders (LR) for the obesity treatment showed lower amplitude and higher
intradaily variability than high responders (HR)
Bandín C, Martinez-Nicolas A, Ordovás JM, Madrid JA, Garaulet M.
Int J Obes (Lond). 2014 Aug;38(8):1083-8.
Organización funcional del ritmo circadiano

Keeping Up With the

Clock Circadian
Disruption and Obesity
Risk. Hypertension,
2016.
 Síntesis de
melatonina

Melatonin and the pineal gland: influence on mammalian seasonal and circadian
physiology. Rev Reprod, 1998
Conexión y coordinación entre los circuitos

Metabolism and the

circadian clock converge.
Physiol Rev, 2013.
 Variación del proteoma durante el día
en estado de sincronización y
desincronización

Mistimed food intake and sleep alters 24-hour time-of-day patterns of the human plasma
proteome. Proceedings of the National Academy of Sciences, 2018
Patrones distintos según la cultura

Human sleep before the industrial era. Nature, 2015.

Cambio cultural e incremento de
la prevalencia de obesidad

NCD Risk Factor Collaboration, 2016.

 Munich Chronotype Questionnaire

Life between clocks: daily temporal patterns of human chronotypes. J. Biol. Rhythms, 2003
 Morningness and Eveningness
Questionnaire

A self-assessment questionnaire to determine morningnesseveningness in human circadian

rhythms. Int. J. Chronobiol
Duración del sueño y cronotipo según la
edad

Epidemiology of the human circadian clock. Sleep Medicine

Reviews, 2007.
 Epidemiología del
cronotipo

A global quantification of “normal” sleep schedules

using smartphone data. Science Advances, 2016
 Variación del proteoma por
desincronización

Mistimed food intake and sleep alters 24-hour time-of-day patterns of the human plasma
proteome. Proceedings of the National Academy of Sciences, 2018
¿Los tiempos
de hábitos de
consumo se
heredan?

Heritability of the timing

of food intake. Clinical
Nutrition, 2018.
 Gasto energético e ingesta
durante el día

Energy balance, body composition, sedentariness and appetite regulation: pathways to obesity. Clinical
Science, 2016.
Efecto del medio ambiente
(2010). Garaulet, M., Ordovás, J. M., & Madrid, J. A. The chronobiology, etiology and pathophysiology of
obesity.
 Cronodisrrupción y alteraciones metabólicas

Keeping Up With the Clock Circadian Disruption Potential role for peripheral circadian clock dyssynchrony in the
pathogenesis of cardiovascular dysfunction. Sleep Med. 2007
and Obesity Risk. Hypertension, 2016.
Patogénesis de obesidad relacionada a la alteración metabólica

Impact of Sleep and Circadian Disruption on Energy Balance and Diabetes:

A Summary of Workshop Discussions. Sleep, 2015.
 Cambio en la expresión de genes relacionados al ritmo circadiano

Circadian misalignment induces fatty acid metabolism gene profiles and compromises insulin sensitivity in
human skeletal muscle. Proceedings of the National Academy of Sciences, 2018.
Diferencias en los tiempos de
comida según el cronotipo

Modifiable lifestyle behaviors, but

not a genetic risk score, associate
with metabolic syndrome in evening
chronotypes. Scientific reports, 2018.
¿Trabajar de noche aumenta
el riesgo cardiometabólico?

Night Shift Work,

Genetic Risk, and
Type 2 Diabetes
in the UK
Biobank. Diabetes
Care, 2018.
 Desayuno y almuerzo más tarde

Porción más grande

Mayor ingesta de comidas ricas en

grasa

Menor cantidad de actividad física

Hora de dormir y despertar más

tarde

Modifiable lifestyle behaviors, but not a genetic risk score,

associate with metabolic syndrome in evening chronotypes.
Scientific reports, 2018.
Dormir menos o más
incrementa el riesgo
cardiovascular

Sleep Duration and

Cardiovascular Disease:
Results from the National
Health
Interview Survey. Sleep, 2010
 Relación de la variabilidad inter-día con el IMC y el
estado físico

Fragmentation of daily rhythms associates with obesity and cardiorespiratory

fitness in adolescents: the HELENA Study. Clinical Nutrition, 2016
 Morning-evening difference in glucose
glucose tolerance in humans (OGTT)
tolerance
Rubio-Sastre et al., Sleep, 2014
MORNING n=21
*EVENING
*
Glucose (mmol/L)

9AM AUC120: P=0.0002

ANOVArm: P=0.002
9 PM AUC120: P=0.0002
ANOVArm: P=0.001

AUC120: P=0.771
ANOVArm: P=0.992
AUC120: P=0.007
Insulin (μU/mL)

ANOVArm: P=0.004

Time (min) Time (min)

 Dinner timing
Cross over randomized study
40 women
AUC120: P=0.002
ANOVArm: P=0.004

*P=0.001
*P=0.000
*P=0.000

*P=0.023

EE: Early eaters

LE: Late eaters

Late dinner produced a decrease in glucose tolerance as compared to

early dinner

Lopez-Minguez J, Saxena R, Bandín C, Scheer FA, Garaulet M., Clin Nutr. 2017
 Higher energy intake at night
five times the probability of being obese
(Evening type)

5 times

Xiao Q, et al., 2019, IJO

 BREAKFAST
If you are morning-type
and have a higher intake during the morning
(2h after wake up)
You double the probability of having a healthy weight

Xiao Q, et al., 2019, IJO

López Minguez, J, Gómez-Abellán P, Garaulet M. Timing
of Breakfast, Lunch, 
and Dinner. Effects on Obesity and Metabolic Risk.
Nutrients 2019, 11(11), 2624
 Relación entre las horas de sueño y
diabetes

The role of sleep duration in diabetes and glucose control. Proceedings of the Nutrition Society,
2016
 Efecto de la desincronización aguda sobre la sensibilidad a la insulina

Circadian misalignment induces fatty acid metabolism gene profiles and compromises insulin sensitivity in
human skeletal muscle. Proceedings of the National Academy of Sciences, 2018.
 Ingesta de polifenoles

Arola-Arnal A, Cruz-Carrión Á, Torres-Fuentes C, et al. Chrononutrition and

Polyphenols: Roles and Diseases. Nutrients. 2019;11(11):2602
 ¿Ayuno intermitente?

Metabolic Effects of Intermittent Fasting. Annual Review of Nutrition, 2017.

 Potenciales mecanismos del
ayuno

Metabolic Effects of Intermittent Fasting. Annual Review of Nutrition, 2017.

 Recomendaciones generales
 Como parte de la intervención nutricional, se debe
considerar el cronotipo de la persona e individualizar el
tiempo de comidas.
 Mantener horarios regulares de sueño.
 Disminuir el estímulo visual electrónico al menos 15
minutos antes de dormir.
 No consumir alimentos abundantes al menos 2 horas
antes del horario habitual de dormir.
 Mantener la habitación ventilada y con el menor ruido
posible.
 Perspectivas futuras
• El beneficio potencial de la cronoterapia como parte del
tratamiento de la obesidad.
• La relevancia del ritmo circadiano en la respuesta a al
farmacoterapia/dietoterapia.
• Salud ocupacional especializada en los trabajadores con
horarios con cambios frecuentes.