2. Diet and sleep
Manolis Kogevinas, MD, PhD
Barcelona Institute for Global Health (ISGlobal)
manolis.kogevinas@isglobal.org
@KogevinasM
3.
4.
5. Carcinogenicity of shift work
IARC (WHO), 2007
“Shift work involving circadian disruption is
probably carcinogenic to humans” (Group 2A)
based on…
• Sufficient evidence from (>20) animal studies
showing the carcinogenicity of light during night
• Limited evidence from epidemiological studies showing
higher risks for breast cancer among female night workers
Straif K et al, 2007; IARC Monographs Vol 98, 2010
6. The effect of circadian rhythm feeding on body
weight in B6 mice (Arble et al 2009)
7. Questions following IARC’s evaluation
• Is this true? (or is this confounding?)
• How big is the risk?
• Is it only breast cancer?
• Is it only cancer?
• What are the mechanisms?
• How do we prevent or minimize effects?
• Legal aspects?
• Does it apply also to the general population?
13. From an evolutionary perspective,
intermittent eating patterns with periods of
fasting were the norm in humans and food
was primarily consumed during daylight with
long hours of overnight fasting.
14. Mechanisms of meal timing relevant to
cancer (and other diseases)
• In human experimental studies, changes in meal
timing were associated with acute effects in leptin
levels, with synchronizing peripheral circadian
rhythms such as glucose levels and with systemic
inflammation.
• In experimental studies, circadian reprogramming
of tumor transcriptome with meal timing was
associated with cancer growth inhibition and
intermittent periods of energy restriction were
found to prevent disease processes
15. Eating Patterns and Lifestyle Factors with C-Reactive Protein
(CRP) and Homeostatic Model Assessment of Insulin
Resistance (HOMA-IR) in Adult Women Participants,
NHANES 2009–2010
16. Separation of circadian- and behavior-driven
metabolite rhythms Cosinor fits for two metabolites. Top:
By circadian time (relative to the timing of melatonin onset,
DLMO). Bottom: By zeitgeber time (i.e., time awake, relative to
lights on) Skene, PNAS, 2018.
Orange/red:
simulated day-shift
condition.
Purple/blue:
simulated night-shift
condition.
17. MCC-Spain Population-based case-
control study in common tumours
• 10 Autonomic Communities
•23 hospitals
• Ages 20-85
• 6105 Incident cases
2200 colon
1721 breast
1152 prostate
496 stomach
536 CLL
• 3898 Population controls
from rosters of selected
Primary Health Care centres
• Response rates controls
between 55% and 80%
18. Effect of mistimed eating on breast and prostate
cancer. Association with time between dinner (last
main meal) and sleeping. MCC-Spain
Adjusted for age, education, menopausal status for breast, smoking, family
history of prostate/breast cancer, BMI, chronotype, WCRF/AICR, Breastfeeding,
parity and centre
Breast Prostate
(Kogevinas, IJC 2018)
19. Association of timing of dinner and sleep interval on
risk of breast and prostate cancer. MCC-Spain study
Breast cancer
OR (95%CI)
Prostate cancer
OR (95%CI)
Combined breast
and prostate
cancer
OR (95%CI)
Dinner/Sleep interval
1 hour or less (ref)
From >1 to ≤2 hrs 0.99 (0.79,1.24) 0.79 (0.62,1.02) 0.89 (0.72,1.11)
More than 2hrs 0.84 (0.67,1.06) 0.74 (0.55,0.99) 0.80 (0.67,0.96)
Time of dinner
10pm or later (ref)
9:00 to <10pm 0.86 (0.70,1.05) 0.88 (0.69,1.12) 0.86 (0.74,1.01)
Before 9pm 0.85 (0.66,1.09) 0.75 (0.53,1.07) 0.82 (0.67,1.00)
20. Distribution of potential risk factors for breast and prostate cancer by
time interval between supper and sleeping (more or less than two
hours) among controls. MCC-Spain study
Women Men
<2h
N=727
>=2h
N=530
<2h
N=625
>=2h
N=210
Educational level
Less than primary school 14% 12% 15% 9%
Primary school 31% 32% 30% 26%
Secondary school 33% 36% 32% 27%
University 22% 21% 22% 38%
Chronotype
Morning type 41% 34% 52% 46%
Intermediate 38% 44% 36% 39%
Evening type 21% 22% 12% 15%
WCRF/AICR
Tertile 1 (low) 40% 40% 40% 40%
Tertile 2 30% 28% 34% 36%
Tertile 3 (high) 30% 32% 25% 24%
21. Time of dinner and risk of breast and prostate cancer.
NutriNet-santé, France
(Srour, IJC 2018)
• 41389 adults, 3 completed 24-hour diet records
• 428 breast cancer cases; 179prostate cancer cases
Dinner after 9:30pm (about 10% of cases)
• Breast cancer HR = 1.48 (95%CI 1.0-2.2)
• Prostate Cancer HR = 2.20 (95%CI 1.3-3.8)
• No association with night fasting duration
• (similar to MCC-Spain and in contrast to circadian
literature on TRE-time restricted eating)
22. www.creal.cat
Chronotype and diurnal preference
Individual chronotype is a human attribute with genetic
basis that reflects the circadian phase of entrainment, i.e.
the timing of the circadian system in entrained conditions
23. Shift work and chronotype: the theory
• Evening types have difficulties in going to bed
earlier at night while working the morning shift
• Morning types experience difficulties in sleeping
during the day while working the night shift
• This means that:
– morning types suffer from a sleep deficit during night
shifts while
– evening types suffer from a sleep deficit during work
on the morning shift
24. Association of timing
of supper and sleep
interval on risk of
breast and prostate
cancer by
chronotype. MCC-
Spain study (n>4000
subjects)
(Kogevinas IJC 2018)
25. Summary, mistimed eating patterns and sleep
• adherence to a more diurnal eating pattern and
specifically an early supper and a long interval between
last meal and sleep are associated with a lower breast
and prostate cancer risk
• hypothesis supported by experimental evidence
• findings stress the importance of evaluating circadian
rhythms and sleep in studies on diet and cancer (and
developing recommendations for prevention not
focusing only on type and quantity of food intake)
26. Mistimed eating patterns and sleep: future steps
• Replicate Spanish and French findings in other
cohorts and evaluate non-cancer endpoints
• Develop molecular epidemiological studies focusing
on pathways using advanced tecniques
• Eventually test interventions (already done in
relatively small scale concerning TRE)
