Taking the Obesity and Diabetes Risk out of Light at Night

Transcription

1 Taking the Obesity and Diabetes Risk out of Light at Night Martin Moore-Ede, M.D., Ph.D. CIRCADIAN Light

2 1980 Discovery: Location of the Human Circadian Clock 2001 Discovery: Blue Light regulates Circadian Clock to maintain health Millions of Years Pineal Melatonin Lydic, Schoene, Czeisler & Moore-Ede (1980) Suprachiasmatic Region of the Human Hypothalamus. Sleep 2: SCN Circadian Clock Bio-Active Blue Light Blue Light iprgc Photoreceptors 100 Years

3 2 Billion Year History: First life used blue light to detect day and night Sunlight at surface 480 Sunlight spectrum 500 m Underwater nm 480nm Gonyaulax Single cell algae Blue photoreceptors Circadian Clock Melatonin Our eyes and bodies use the same blue spectrum today to detect day and night

4 The Drive for Energy Efficiency has immersed us in Blue-Rich Light SB SUNLIGHT 25% By % of the Global Market will be LED Light* 20% 15% 5% * Boston Consulting Group Circadian Bio-Active Blue Dose = SB x I SB = Spectrum (Percent Bio-Active Blue) I = Intensity (Total Visible Irradiance)

5 Daytime Blue-Rich Light Boosts Human Alertness and Performance DAY SHIFT 8:30AM 4:45PM Sleep Disruption Viola AU et al (2008) Blue-enriched white light in the workplace improves self-reported alertness, performance and sleep quality. Scand J Work Environ Health 34(4):

6 Blue Light at Night Disrupts the Circadian Clock and Impairs Health Shiftwork that involves circadian disruption is probably carcinogenic to humans Epidemiological studies have found that longterm night-workers have a higher risk of breast cancer risk than women who do not work at night. These studies have involved mainly nurses and flight attendants. The studies are consistent with animal studies that demonstrate that constant light, dim light at night, or simulated Chronic jet lag can substantially increase tumour development. Other experimental studies show that reducing melatonin levels at night increases the incidence or growth of tumours. The primary human concern with nighttime lighting include potential carcinogenic effects related to melatonin suppression, especially breats cancer. Other diseases that may be exacerbated by circadian disruption include: Obesity Diabetes Depression Mood Disorders Reproductive problems NIH Workshop: Shift Work at Night, Artificial Light at Night, and Circadian Disruption Exposures to artificial light at night (ALAN) or changes in the timing of exposures to natural light (such as with jet lag ) may disrupt biological processes controlled by endogenous circadian rhythms, potentially resulting in adverse health outcomes. NTP is interested in understanding the health effects of circadian disruption related to ALAN and shift work. NTP s Office of the Report on Carcinogens (ORoC) and Office of Health Assessment and Translation (OHAT) plan to conduct health hazard assessments focusing on cancer (ORoC) and non-cancer health outcomes (OHAT).

7 Blue Light at Night Causal Chain: Breast and Prostate Cancer White LED and Florescent Light Contains High Bio-Active Blue ( nm) Content Melanopsin receptors in lower half of eye retina detect Bio-Active Blue Light Blue Light AT NIGHT disrupts timing of Circadian Clock Blue Light AT NIGHT suppresses Melatonin release from Pineal Gland Cancer Tumors Grow Faster when Melatonin is Suppressed Increased Rate of Breast Cancer and Prostate Cancer In People Working at Night Nakamura, S (2015) Rev. Mod. Phys. 87, Bailes, HJ & Lucas, RJ (2013). Proc. Roy. Soc. B. 280: , 1-9 Lockley SW, et al. (2003) J Clin Endocrinol Metab 88: Brainard GC et al (2001) J.Neuroscience, 21: Blask D.E. et al (2005) Cancer Res 65: Hansen, J (2001) Epidemiology 12: Stevens R et al (2014) CA Cancer J 64: Glickman, G et al (2003) J Biol. Rhy. 18: Ruger, M et al (2013) J Physiol. 591: West KE et al (2011) J Appl Physiol 110: , Hill SM et al, (2015) Endocrine-Related Cancer 22, R183 R204 Kubo T et al Am J Epidemiol (2006) 164:

8 Cost of Circadian Disruption by Light at Night is Far Broader than Health Risks $11,200 excess cost per employee per year of circadian disruption in 24/7 shift employees as compared to equivalent daytime 9-5 workforce Kerin & Carbone (2003), Shiftwork Practices (2017)

9 LED use at night is accelerating the Diabetes and Obesity Epidemic 9.3% of the US population is diabetic, costing $245 Billion per year1,2,3,4 Light exposure in evening and at night increases Diabetes Risk by 37% in men (meta-analysis of 12 studies 240,000 people)5 Insulin resistance develops within 1-2 nights of light exposure CDC (2004) Estimates of Diabetes and Its Burden in the United States. National Diabetes Statistics Report Selvin E, et al (2014) Trends in prevalence and control of diabetes in the United States, & Ann Intern Med 160: American Heart Association (2017) American Diabetes Association (2015) Gan Y et al (2015) Shift work and diabetes mellitus: a meta-analysis of observational studies Occup Environ Med 72: Leproult et al (2014) Circadian Misalignment Augments Markers of Insulin Resistance and Inflammation, Independently of Sleep Loss Diabetes 63:

10 Blue Rich Light at Night Causal Chain: Obesity and Diabetes White LED and Florescent Light Contains High Bio-Active Blue Content Melanopsin receptors in lower half of eye retina detect Bio-Active Blue Light Blue Light AT NIGHT disrupts timing of Circadian Clock Circadian Disruption of Insulin Release from Pancreatic Beta Cells Increased Appetite Obesity & Insulin Resistance Increased Incidence of Diabetes In People Working under Light at Night Nakamura, S (2015) Rev. Mod. Phys. 87, Bailes, HJ & Lucas, RJ (2013). Proc. Roy. Soc. B. 280: , 1-9 Lockley SW, et al. (2003) J Clin Endocrinol Metab 88: Qian J et al (2013) Diabetes 62: Leproult et al (2014) Diabetes 63: Gan Y et al (2015) Occup Environ Med 72: Stevens R et al (2014) CA Cancer J 64: Glickman, G et al (2003) J Biol. Rhy. 18: Ruger, M et al (2013) J Physiol. 591: Light at Night causes Diminished GlucoseStimulated Insulin Secretion Insulin Resistance caused by Circadian Disruption and not sleep loss Meta analysis of 12 studies showing 37% increase in men

11 Hypothesis: Diabetes & Obesity Risk can be prevented by removing blue from light at night White LED and Florescent Light Contains High Bio-Active Blue Content Remove Bio-Active Blue from White Light Spectrum AT NIGHT Melanopsin receptors in lower half of eye retina detect Bio-Active Blue Light Blue Light AT NIGHT disrupts timing of Circadian Clock Prevent Circadian Clock Disruption HYPOTHESIS Circadian Disruption of Insulin Release from Pancreatic Beta Cells Increased Appetite & Insulin Resistance Reduce Appetite Prevent Insulin Resistance Increased Incidence of Obesity & Diabetes In People Working under Light at Night Reduce Obesity and Diabetes Risk

12 CIRCADIAN Light Medical Research Center: Human Validation Studies Human volunteers live and work 24/7 in a light controlled facility Sleep Lab facility including EEG Blood tests (lipids, cardiac markers) Glucose Tolerance tests (Diabetes) 24 hour urine melatonin collection Salivary Melatonin 30 minute intervals Blood pressure Alertness & performance tests Mood and Depression scale test Human Subject testing under IRB approval

13 Comparison of Blue-Rich and Blue-Depleted White LED Lights at Night Conventional Blue-Rich LED Conventional Blue-Pump LED Bio-Active Blue CIRCADIAN Blue-Depleted LED Bio-Active Blue CIRCADIAN Night LED Radiant Flux (µw/nm) % 3900K Radiant Flux (µw/nm) % 3200K Wavelength (nm) Wavelength (nm)

14 Study of Impact of Conventional LED Lights at Night on Insulin Resistance 11 healthy male volunteers Established 7 day baseline 11pm 7am sleep and wake schedule On first night obtained 11pm to 7am baseline sleep EEG in dark room On nights 2 and 3, subjects worked 12 hour overnight shifts (19:00 07:00) illuminated by conventional white LED lights at 540 lux At 8am after baseline night sleep, and after each 12 hour night shifts Fasting blood glucose and insulin levels obtained Standardized breakfast plus 50g glucose meal (960 calories) Glucose and Insulin levels were measured at 30, 60, 90 and 120 minutes

15 Conventional Blue-Rich LEDs Increase Insulin Resistance after only Two Night Shifts Daily response to 8am Breakfast + 50 g Glucose Meal Light at Night: Conventional LED (Blue-Rich) Darkness (Sleep) Blood Insulin Insulin [IU/ml] - AUC (2 hours) Morning 1 (Night Sleep) ** ** * Morning 2 (Night Shift 1) Morning 3 (Night Shift 2) n=11

16 Study Comparing Blue-Rich and Blue-Depleted Light at Night 6 healthy male volunteers in two visits in a cross over study design Established 7 day baseline 11pm 7am sleep and wake schedule On first night obtained 11pm to 7am baseline sleep EEG in dark room On nights 2 and 3, subjects worked 12 hour overnight shifts (19:00 07:00) illuminated by: Visit One: Conventional white LED lights at 540 lux (20% bio-active blue) Visit Two: Blue-Depleted white LED lights at 540 lux (2% bio-active blue) At 8am fasting blood glucose and insulin levels obtained after baseline night sleep and after each 12 hour night shifts Glucose tolerance was determined at 30, 60, 90 & 120 minutes after standardized breakfast plus 50g glucose meal (960 calories) Circadian phase was evaluated with hourly salivary melatonin levels Performance levels measured by hourly PVT reaction time and lapses

17 Circadian System Disruption with Blue-Rich Light Prevented by Removing Blue Light at Night: CIRCADIAN Night LED (BioActive Blue Depleted) Conventional LED (Blue-Rich) 20 DIM Light Night Shift 1 Night Shift 2 n=6 Melatonin (pg/ml) NIGHT SLEEP DAY SLEEP DAY SLEEP Time of Day

18 Conventional LEDs Increase Appetite Reversed by CIRCADIAN LEDs CIRCADIAN Light Removes Bio-Active Blue at Night Light at Night: CIRCADIAN Night LED (Bio-Active Blue Depleted) Conventional LED (Blue-Rich) Appetite (VAS) * * Bio-Active Blue 0 04:00 06:00 Time of Night

19 Conventional LEDs Increase Insulin Resistance Reversed by CIRCADIAN LEDs Insulin [µiu/ml] - AUC (2 hours) Light at Night: CIRCADIAN Night LED (Bio-Active Blue Depleted) Conventional LED (Blue-Rich) Dark (Sleep) Morning After Night Sleep (Baseline) ** Morning After 2nd Night Shift

20 Performance is Maintained with Blue-Depleted White Light at Night 25 Light at Night: PVT - Lapses CIRCADIAN Night LED (Bio-Active Blue Depleted) Conventional LED (Blue-Rich) Incandescent Dim :00 06:00 Time of Night

21 Study Conclusions 1. Bio-active blue rich light at night results in increased appetite and insulin resistance 2. These changes are consistent with the increased risk of obesity and diabetes among night workers 3. White light depleted of bioactive blue ameliorates both increased appetite and insulin resistance without loss of human vigilance & performance

22 Human health and well being requires lights which regulate blue light dosage by time of day, season and location Add daytime blue content to boost productivity Remove blue at night to protect health Blue Benefits Increased Alertness Increased Vigilance Increased Productivity Sleep Improvement Mood Improvement Health Improvement Blue Costs Sleep Disruption Breast/prostate/colon cancers Obesity/diabetes Type 2 metabolic syndrome Cardiovascular disease Depression/mood disorder