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melatonin directory


“Evening Home Lighting Adversely Impacts the Circadian System and Sleep”, Cain et al 2020

“Evening home lighting adversely impacts the circadian system and sleep”⁠, Sean W. Cain, Elise M. McGlashan, Parisa Vidafar, Jona Mustafovska, Simon P. N. Curran, Xirun Wang, Anas Mohamed et al (2020-11-05; ; backlinks; similar):

The regular rise and fall of the sun resulted in the development of 24-h rhythms in virtually all organisms. In an evolutionary heartbeat, humans have taken control of their light environment with electric light. Humans are highly sensitive to light, yet most people now use light until bedtime.

We evaluated the impact of modern home lighting environments in relation to sleep and individual-level light sensitivity using a new wearable spectrophotometer. We found that nearly half of homes had bright enough light to suppress melatonin by 50%, but with a wide range of individual responses (0–87% suppression for the average home). Greater evening light relative to an individual’s average was associated with increased wakefulness after bedtime.

Homes with energy-efficient lights had nearly double the melanopic illuminance of homes with incandescent lighting. These findings demonstrate that home lighting substantially affects sleep and the circadian system, but the impact of lighting for a specific individual in their home is highly unpredictable.

“The Effects of Blue-Light Filtration on Sleep and Work Outcomes”, Guarana et al 2020

2021-guarana.pdf: “The Effects of Blue-Light Filtration on Sleep and Work Outcomes”⁠, Cristiano L. Guarana, Christopher M. Barnes, Wei Jee Ong (2020-07-13; ; similar):

In this article, we investigate the effects of blue-light filtration on broad attitudinal and behavioral outcomes (ie. work engagement, organizational citizenship behavior, and counterproductive work behavior).

Drawing on recent developments in the circadian process literature and its related research on chronobiology⁠, we propose that a cost-effective sleep intervention can improve multiple organizationally relevant outcomes. Specifically, we theorize that wearing blue-light filtering glasses creates a form of physiologic darkness, thus improving both sleep quantity and quality. We then argue that wearing blue-light filtering glasses is related to work engagement, task performance, and nontask performance via sleep quantity and sleep quality. Considering that individuals vary in the timing of their circadian process, we propose that chronotype is a first-stage moderator for our theoretical model.

We tested these theoretical expectations in 2 experimental experience sampling studies. In Study 1a, we collected data from 63 managers (519 daily observations) and found that wearing blue-light filtering glasses is an effective intervention to improve physiological (sleep), attitudinal (work engagement), and behavioral (task performance, organizational citizenship behavior, and counterproductive work behavior) outcomes. In general, the effects were stronger for employees who tend to have sleep periods later in the day.

In Study 1b, we collected data from 67 call center representatives (529 daily observations) and measured task performance from clients. We replicated most of the findings except for the interactions.

Our model highlights how and when wearing blue-light filtering glasses can help employees to live and work better.

[Keywords: circadian process, sleep, well-being, work engagement, task and nontask performance]

“Interplay of Chronotype and School Timing Predicts School Performance”, Goldin et al 2020

2020-goldin.pdf: “Interplay of chronotype and school timing predicts school performance”⁠, Andrea P. Goldin, Mariano Sigman, Gisela Braier, Diego A. Golombek, María J. Leon (2020-02-10; ; backlinks; similar):

Most adolescents exhibit very late chronotypes and attend school early in the morning, a misalignment that can affect their health and psychological well-being. Here we examine how the interaction between the chronotype and school timing of an individual influences academic performance, studying an unique sample of 753 Argentinian students who were randomly assigned to start school in the morning (07:45), afternoon (12:40) or evening (17:20). Although chronotypes tend to align partially with class time, this effect is insufficient to fully account for the differences with school start time. We show that (1) for morning-attending students, early chronotypes perform better than late chronotypes in all school subjects, an effect that is largest for maths; (2) this effect vanishes for students who attend school in the afternoon; and (3) late chronotypes benefit from evening classes. Together, these results demonstrate that academic performance is improved when school times are better aligned with the biological rhythms of adolescents.

“Vitamin C and E Supplementation Hampers Cellular Adaptation to Endurance Training in Humans: a Double-blind, Randomised, Controlled Trial”, Paulsen et al 2014

2014-paulsen.pdf: “Vitamin C and E supplementation hampers cellular adaptation to endurance training in humans: a double-blind, randomised, controlled trial”⁠, Gøran Paulsen, Kristoffer T. Cumming, Geir Holden, Jostein Hallén, Bent Ronny Rønnestad, Ole Sveen, Arne Skaug et al (2014-03-03; ; backlinks; similar):

  • Recent studies have indicated that antioxidant supplementation may blunt adaptations to exercise, such as mitochondrial biogenesis induced by endurance training. However, studies in humans are sparse and results are conflicting.
  • Isolated vitamin C and E supplements are widely used, and unravelling the interference of these vitamins in cellular and physiological adaptations to exercise is of interest to those who exercise for health purposes and to athletes.
  • Our results show that vitamin C and E supplements blunted the endurance training-induced increase of mitochondrial proteins (COX4), which is important for improving muscular endurance.
  • Training-induced increases in VO2max and running performance were not detectably affected by the supplementation.
  • The present study contributes to understanding of how antioxidants may interfere with adaptations to exercise in humans, and the results indicate that high dosages of vitamins C and E should be used with caution.

In this double-blind, randomised, controlled trial⁠, we investigated the effects of vitamin C and E supplementation on endurance training adaptations in humans. Fifty-four young men and women were randomly allocated to receive either 1000 mg of vitamin C and 235 mg of vitamin E or a placebo daily for 11 weeks. During supplementation, the participants completed an endurance training programme consisting of three to four sessions per week (primarily of running), divided into high-intensity interval sessions [4–6 × 4–6 min; >90% of maximal heart rate (HRmax)] and steady state continuous sessions (30–60 min; 70–90% of HRmax). Maximal oxygen uptake (VO2max), submaximal running and a 20 m shuttle run test were assessed and blood samples and muscle biopsies were collected, before and after the intervention. Participants in the vitamin C and E group increased their VO2max (mean ± s.d.: 8 ± 5%) and performance in the 20 m shuttle test (10 ± 11%) to the same degree as those in the placebo group (mean ± s.d.: 8 ± 5% and 14 ± 17%, respectively). However, the mitochondrial marker cytochrome c oxidase subunit IV (COX4) and cytosolic peroxisome proliferator-activated receptor-γ coactivator 1 α (PGC-1α) increased in the m. vastus lateralis in the placebo group by 59 ± 97% and 19 ± 51%, respectively, but not in the vitamin C and E group (COX4: −13 ± 54%; PGC-1α: −13 ± 29%; p ≤ 0.03, between groups). Furthermore, mRNA levels of CDC42 and mitogen-activated protein kinase 1 (MAPK1) in the trained muscle were lower in the vitamin C and E group than in the placebo group (p ≤ 0.05). Daily vitamin C and E supplementation attenuated increases in markers of mitochondrial biogenesis following endurance training. However, no clear interactions were detected for improvements in VO2max and running performance. Consequently, vitamin C and E supplementation hampered cellular adaptations in the exercised muscles, and although this did not translate to the performance tests applied in this study, we advocate caution when considering antioxidant supplementation combined with endurance exercise.

“Blue Blocker Glasses As a Countermeasure for Alerting Effects of Evening Light-Emitting Diode Screen Exposure in Male Teenagers”, Sc. et al 2014

2014-lely.pdf: “Blue Blocker Glasses as a Countermeasure for Alerting Effects of Evening Light-Emitting Diode Screen Exposure in Male Teenagers”⁠, Stéphanie van der Lely M. Sc., Silvia Frey, Corrado Garbazza, Anna Wirz-Justice, Oskar G. Jenni, Rol et al (2014-01-01; backlinks)

“The Therapeutic or Prophylactic Effect of Exogenous Melatonin against Depression and Depressive Symptoms: A Systematic Review and Meta-analysis”, Hansen et al 2014

2014-hansen.pdf: “The therapeutic or prophylactic effect of exogenous melatonin against depression and depressive symptoms: A systematic review and meta-analysis”⁠, M. V. Hansen, A. K. Danielsen, I. Hageman, J. Rosenberg, I. Gögenur (2014-01-01; backlinks)

“Meta-Regression Analyses, Meta-Analyses, and Trial Sequential Analyses of the Effects of Supplementation With Beta-Carotene, Vitamin A, and Vitamin E Singly or in Different Combinations on All-Cause Mortality: Do We Have Evidence for Lack of Harm?”, Bjelakovic et al 2013

“Meta-Regression Analyses, Meta-Analyses, and Trial Sequential Analyses of the Effects of Supplementation with Beta-Carotene, Vitamin A, and Vitamin E Singly or in Different Combinations on All-Cause Mortality: Do We Have Evidence for Lack of Harm?”⁠, Goran Bjelakovic, Dimitrinka Nikolova, Christian Gluud (2013-08-04; backlinks; similar):

Background and Aims: Evidence shows that antioxidant supplements may increase mortality. Our aims were to assess whether different doses of beta-carotene, vitamin A, and vitamin E affect mortality in primary and secondary prevention randomized clinical trials with low risk of bias.

Methods: The present study is based on our 2012 Cochrane systematic review analyzing beneficial and harmful effects of antioxidant supplements in adults. Using random-effects meta-analyses⁠, meta-regression analyses, and trial sequential analyses, we examined the association between beta-carotene, vitamin A, and vitamin E, and mortality according to their daily doses and doses below and above the recommended daily allowances (RDA).

Results: We included 53 randomized trials with low risk of bias (241,883 participants, aged 18 to 103 years, 44.6% women) assessing beta-carotene, vitamin A, and vitamin E. Meta-regression analysis showed that the dose of vitamin A was statistically-significantly positively associated with all-cause mortality. Beta-carotene in a dose above 9.6 mg statistically-significantly increased mortality (relative risk (RR) 1.06, 95% confidence interval (CI) 1.02 to 1.09, I2 = 13%). Vitamin A in a dose above the RDA (> 800 µg) did not statistically-significantly influence mortality (RR 1.08, 95% CI 0.98 to 1.19, I2 = 53%). Vitamin E in a dose above the RDA (> 15 mg) statistically-significantly increased mortality (RR 1.03, 95% CI 1.00 to 1.05, I2 = 0%). Doses below the RDAs did not affect mortality, but data were sparse.

Conclusions: Beta-carotene and vitamin E in doses higher than the RDA seem to statistically-significantly increase mortality, whereas we lack information on vitamin A. Dose of vitamin A was statistically-significantly associated with increased mortality in meta-regression. We lack information on doses below the RDA.

Background: All essential compounds to stay healthy cannot be synthesized in our body. Therefore, these compounds must be taken through our diet or obtained in other ways. Oxidative stress has been suggested to cause a variety of diseases. Therefore, it is speculated that antioxidant supplements could have a potential role in preventing diseases and death. Despite the fact that a normal diet in high-income countries may provide sufficient amounts of antioxidants, more than one third of adults regularly take antioxidant supplements.

“Entrainment of the Human Circadian Clock to the Natural Light-Dark Cycle”, Jr. et al 2013

2013-wright.pdf: “Entrainment of the Human Circadian Clock to the Natural Light-Dark Cycle”⁠, Kenneth P. Wright Jr., Andrew W. McHill, Brian R. Birks, Brandon R. Griffin, Thomas Rusterholz, Evan D. Chinoy et al (2013-01-01; backlinks)

“Exposure to Bright Light during Evening Class Hours Increases Alertness among Working College Students”, Teixeira et al 2013

2013-teixeira.pdf: “Exposure to bright light during evening class hours increases alertness among working college students”⁠, Liliane Teixeira, Arne Lowden, Andréa Aparecida da Luz, Samantha Lemos Turte, Claudia Roberta Moreno et al (2013-01-01; backlinks)

“Effects of LED-Backlit Computer Screen and Emotional Self-Regulation on Human Melatonin Production”, Sroykham & Wongsawat 2013

2013-sroykham.pdf: “Effects of LED-Backlit Computer Screen and Emotional Self-Regulation on Human Melatonin Production”⁠, Watchara Sroykham, Yodchanan Wongsawat (2013-01-01; backlinks)

“TF-TPDR120086 1..8 ++”, Murdoch-Eaton 2013

2013-keegan.pdf: “TF-TPDR120086 1..8 ++”⁠, Lisa-Jane Keegan Rosa Reed-Berendt Elizabeth Neilly Matthew C. H. J. Morrall Deborah Murdoch-Eaton (2013-01-01; backlinks)

“Total Sleep Time Severely Drops during Adolescence”, Leger et al 2012

“Total Sleep Time Severely Drops during Adolescence”⁠, Damien Leger, François Beck, Jean-Baptiste Richard, Emmanuelle Godeau (2012-08-17; backlinks; similar):

Restricted sleep duration among young adults and adolescents has been shown to increase the risk of morbidities such as obesity, diabetes or accidents. However there are few epidemiological studies on normal total sleep time (TST) in representative groups of teen-agers which allow to get normative data.

Purpose :

To explore perceived total sleep time on schooldays (TSTS) and non schooldays (TSTN) and the prevalence of sleep initiating insomnia among a nationally representative sample of teenagers.

Methods :

Data from 9,251 children aged 11 to 15 years-old, 50.7% of which were boys, as part of the cross-national study 2011 HBSC were analyzed. Self-completion questionnaires were administered in classrooms. An estimate of TSTS and TSTN (week-ends and vacations) was calculated based on specifically designed sleep habits report. Sleep deprivation was estimated by a TSTN—TSTS difference >2 hours. Sleep initiating nsomnia was assessed according to International classification of sleep disorders (ICSD 2). Children who reported sleeping 7 hours or less per night were considered as short sleepers.

Results :

A serious drop of TST was observed between 11 yo and 15 yo, both during the schooldays (9 hours 26 minutes vs. 7 h 55 min.; p < 0.001) and at a lesser extent during week-ends (10 h 17 min. vs. 9 h 44 min.; p < 0.001). Sleep deprivation concerned 16.0% of chidren aged of 11 yo vs. 40.5% of those of 15 yo (p < 0.001). Too short sleep was reported by 2.6% of the 11 yo vs. 24.6% of the 15 yo (p < 0.001).

Conclusion :

Despite the obvious need for sleep in adolescence, TST drastically decreases with age among children from 11 to 15 yo which creates significant sleep debt increasing with age.

“Morningness-eveningness and Educational Outcomes: the Lark Has an Advantage over the Owl at High School”, Preckel et al 2012

2013-preckel.pdf: “Morningness-eveningness and educational outcomes: the lark has an advantage over the owl at high school”⁠, Franzis Preckel, Anastasiya A. Lipnevich, Katharina Boehme, Lena Brandner, Karsten Georgi, Tanja Könen et al (2012-01-02; ; backlinks; similar):

Background: Chronotype refers to individuals’ preference for morning or evening activities. Its two dimensions (morningness and eveningness) are related to a number of academic outcomes.

Aims: The main goal of the study was to investigate the incremental validity of chronotype as a predictor of academic achievement after controlling for a number of traditional predictors. In so doing, a further aim was ongoing validation of a chronotype questionnaire, the Lark-Owl Chronotype Indicator.

Sample: The sample comprised 272 students attending 9th and 10th grades at five German high schools. Data was also obtained from 132 parents of these students.

Method: Students were assessed in class via self-report questionnaires and a standardized cognitive test. Parents filled out a questionnaire at home. The incremental validity of chronotype was investigated using hierarchical linear regression. Validity of the chronotype questionnaire was assessed by correlating student ratings of their chronotype with behavioural data on sleep, food intake, and drug consumption and with parent ratings of chronotype.

Results: Eveningness was a statistically-significant (negative) predictor of overall grade point average (GPA), math-science GPA, and language GPA, after cognitive ability, conscientiousness⁠, need for cognition, achievement motivation, and gender were held constant. Validity evidence for the chronotype measure was established by statistically-significant correlations with parent-ratings and behavioural data.

Conclusions: Results point to the possible discrimination of adolescents with a proclivity towards eveningness at school. Possible explanations for the relationship between chronotype and academic achievement are presented. Implications for educational practice are also discussed.

“Light Level and Duration of Exposure Determine the Impact of Self-luminous Tablets on Melatonin Suppression”, Wood et al 2012

2012-wood.pdf: “Light level and duration of exposure determine the impact of self-luminous tablets on melatonin suppression”⁠, Brittany Wood, Mark S. Rea, Barbara Plitnick, Mariana G. Figueiro, Mark S. Rea, Barbara Plitnick, Mariana G. Figueiro et al (2012-01-01; backlinks)

“Pharmacological and Non-pharmacological Management of Sleep Disturbance in Children: An Australian Paediatric Research Network Survey”, Heussler et al 2012

2012-heussler.pdf: “Pharmacological and non-pharmacological management of sleep disturbance in children: An Australian Paediatric Research Network survey”⁠, Helen Heussler, Patrick Chan, Anna M. H. Price, Karen Waters, Margot J. Davey, Harriet Hiscock (2012-01-01; backlinks)

“An Exploratory Study of Combination Buspirone and Melatonin SR in Major Depressive Disorder (MDD): A Possible Role for Neurogenesis in Drug Discovery”, Fava et al 2012

2012-fava.pdf: “An exploratory study of combination buspirone and melatonin SR in Major Depressive Disorder (MDD): A possible role for neurogenesis in drug discovery”⁠, Maurizio Fava, Steven D. Targum, Andrew A. Nierenberg, Leo S. Bleicher, Todd A. Carter, Pamela C. Wedel et al (2012-01-01; backlinks)

“Can Small Shifts in Circadian Phase Affect Performance?”, Burgess et al 2012

2012-burgess.pdf: “Can small shifts in circadian phase affect performance?”⁠, Helen J. Burgess, Carlo S. Legasto, Louis F. Fogg, Mark R. Smith (2012-01-01; backlinks)

“Chronic Dim Light at Night Provokes Reversible Depression-like Phenotype: Possible Role for TNF”, Bedrosian et al 2012

2012-bedrosian.pdf: “Chronic dim light at night provokes reversible depression-like phenotype: possible role for TNF”⁠, T A. Bedrosian, Z. M Weil, R. J Nelson (2012-01-01; backlinks)

“A Randomized Experiment to Examine Unintended Consequences of Dietary Supplement Use among Daily Smokers: Taking Supplements Reduces Self-regulation of Smoking”, Chiou et al 2011

2011-chiou.pdf: “A randomized experiment to examine unintended consequences of dietary supplement use among daily smokers: taking supplements reduces self-regulation of smoking”⁠, Wen-Bin Chiou, Chin-Sheng Wan, Wen-Hsiung Wu, King-Teh Lee (2011-08-02; ⁠, ; backlinks; similar):

Aims: We examined whether smokers’ use of dietary supplements (eg. vitamin C⁠, multi-vitamins) induces illusory invulnerability that in turn disinhibits smoking. Such supplement use may be perceived as conferring health credentials.

Design: A single-factor (credentials: with or without) between-subjects design was employed. Smokers were assigned randomly to take either a known placebo pill or a dietary supplement (in fact, the same placebo) in an ostensible health-food test.

Setting: Laboratory at Kaohsiung Medical University⁠, Taiwan⁠.

Participants: Study 1 involved of a student sample consisting of 74 daily smokers, whereas study 2 involved a community sample consisting of 80 daily smokers.

Measurements: In Study 1, participants reported their perceived invulnerability following the manipulation. In study 2, pre-test and post-test measures of invulnerability were administered, and attitudes towards dietary supplements were assessed prior to the manipulation. In both studies, the dependent measure was the number of cigarettes smoked during completion of an unrelated survey.

Findings: Participants who believed that they were taking a dietary supplement smoked more cigarettes than did controls. Study 1 found support for the role of perceived invulnerability as a mechanism underlying this effect. Study 2 demonstrated the moderating effect played by attitudes towards dietary supplements: a more positive attitude towards supplements increased susceptibility to licensing effects⁠.

Conclusions: Dietary supplement use may create illusory invulnerability, reducing the self-regulation of smoking. Reminding health-conscious smokers that multi-vitamins do not prevent cancer may help such smokers to control their smoking and encourage them to stop.

[Keywords: attitudes towards dietary supplements, invulnerability, licensing, smoking]

“Relationships between Hours of Sleep and Health-risk Behaviors in US Adolescent Students”, McKnight-Eily et al 2011

2011-mcknighteily.pdf: “Relationships between hours of sleep and health-risk behaviors in US adolescent students”⁠, Lela R. McKnight-Eily, Danice K. Eaton, Richard Lowry, Janet B. Croft, Letitia Presley-Cantrell, Geraldine S. Perry et al (2011-01-01; backlinks)

“Novel Melatonin-based Therapies: Potential Advances in the Treatment of Major Depression”, Hickie & Rogers 2011

2011-hickie.pdf: “Novel melatonin-based therapies: potential advances in the treatment of major depression”⁠, Ian B. Hickie, Naomi L. Rogers (2011-01-01; backlinks)

“Limiting the Impact of Light Pollution on Human Health, Environment and Stellar Visibility”, Falchi et al 2011

2011-falchi.pdf: “Limiting the impact of light pollution on human health, environment and stellar visibility”⁠, Fabio Falchi, Pierantonio Cinzano, Christopher D. Elvidge, David M. Keith, Abraham Haim (2011-01-01; backlinks)

“Zeo Sleep Self-experiments”, Branwen 2010

Zeo: “Zeo sleep self-experiments”⁠, Gwern Branwen (2010-12-28; ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ; backlinks; similar):

EEG recordings of sleep and my experiments with things affecting sleep quality or durations: melatonin, potassium, vitamin D etc

I discuss my beliefs about Quantified Self⁠, and demonstrate with a series of single-subject design self-experiments using a Zeo. A Zeo records sleep via EEG; I have made many measurements and performed many experiments. This is what I have learned so far:

  1. the Zeo headband is wearable long-term
  2. melatonin improves my sleep
  3. one-legged standing does little
  4. Vitamin D at night damages my sleep & Vitamin D in morning does not affect my sleep
  5. potassium (over the day but not so much the morning) damages my sleep and does not improve my mood/​productivity
  6. small quantities of alcohol appear to make little difference to my sleep quality
  7. I may be better off changing my sleep timing by waking up somewhat earlier & going to bed somewhat earlier
  8. lithium orotate does not affect my sleep
  9. Redshift causes me to go to bed earlier
  10. ZMA: inconclusive results slightly suggestive of benefits

“Prolonged Release Melatonin in the Treatment of Primary Insomnia: Evaluation of the Age Cut-off for Short-term and Long-term Response”, Wade et al 2010

2011-wade.pdf: “Prolonged release melatonin in the treatment of primary insomnia: evaluation of the age cut-off for short-term and long-term response”⁠, Alan G. Wade, Gordon Crawford, Ian Ford, Alex McConnachie, Tali Nir, Moshe Laudon, Nava Zisapel (2010-11-24; backlinks; similar):

Objectives: The authors recently reported on efficacy and safety of prolonged-release melatonin formulation (PRM; Circadin 2 mg) in elderly insomnia patients. The age cut-off for response to PRM and the long-term maintenance of efficacy and safety were further evaluated by looking at the total cohort (age 18–80 years) from that study and subsets of patients aged 18–54 and 55–80 years (for whom the drug is currently indicated).

Design: Randomised, double-blind, placebo controlled trial.

Setting: Multicentre, outpatients, primary care setting.

Methods: A total of 930 males and females aged 18–80 years with primary insomnia who reported mean nightly sleep latency (SL) >20 min were enrolled and 791 entered the active phase of the study. The study comprised a 2-week, single-blind placebo run-in period followed by 3 week’s double-blind treatment with PRM or placebo, one tablet per day at 2 hours before bedtime. PRM patients continued whereas placebo completers were re-randomised 1:1 to PRM or placebo for 26 weeks followed by 2-weeks run-out on placebo.

Main Outcome Measures: SL and other sleep variables derived from sleep diary, Pittsburgh Sleep Quality Index (PSQI), Quality of life (WHO-5), Clinical Global Impression of Improvement (CGI-I) and adverse effects, recorded each visit, withdrawal and rebound effects during run-out.

Results: In all, 746 patients completed the 3-week and 555 (421 PRM, 134 placebo) completed the 6-month period. The principal reason for drop-out was patient decision. At 3 weeks, statistically-significant differences in SL (diary, primary variable) in favour of PRM vs. placebo treatment were found for the 55–80-year group (−15.4 vs. −5.5 min, p = 0.014) but not the 18–80-year cut-off which included younger patients. Other variables (SL-PSQI, PSQI, WHO-5, CGI-I scores) improved statistically-significantly with PRM in the 18–80-year population, more so than in the 55–80-year age group. Improvements were maintained or enhanced over the 6–month period with no signs of tolerance. No withdrawal symptoms or rebound insomnia were detected. Most adverse events were mild with no statistically-significant differences between PRM and placebo groups in any safety outcome.

Conclusions: The results demonstrate short-term and long-term efficacy of PRM in insomnia patients aged 18–80 years, particularly those aged 55 and over. PRM was well-tolerated over the entire 6-month period with no rebound or withdrawal symptoms following discontinuation.

Trial Registration: identifier: NCT00397189.

[Keywords: melatonin, insomnia, long-term, prolonged-release, sleep latency]

“Dual N-Back FAQ”, Branwen 2009

DNB-FAQ: “Dual n-Back FAQ”⁠, Gwern Branwen (2009-03-25; ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ; backlinks; similar):

A compendium of DNB, WM⁠, IQ information up to 2015.

Between 2008 and 2011, I collected a number of anecdotal reports about the effects of n-backing; there are many other anecdotes out there, but the following are a good representation—for what they’re worth.

“Modafinil”, Branwen 2009

Modafinil: “Modafinil”⁠, Gwern Branwen (2009-02-20; ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ; backlinks; similar):

Effects, health concerns, suppliers, prices & rational ordering.

Modafinil is a prescription stimulant drug. I discuss informally, from a cost-benefit-informed perspective, the research up to 2015 on modafinil’s cognitive effects, the risks of side-effects and addiction/​tolerance and law enforcement, and give a table of current grey-market suppliers and discuss how to order from them.


2009-burkhart.pdf: “AMBER LENSES TO BLOCK BLUE LIGHT AND IMPROVE SLEEP: A RANDOMIZED TRIAL”⁠, Burkhart Kimberly Phelps James R. (2009-01-01; backlinks)

“CNS Drugs 2007; 21 (12): 995-1018”, Cardinali 2007

2007-pandiperumal.pdf: “CNS Drugs 2007; 21 (12): 995-1018”⁠, SR Pandi-Perumal V. Srinivasan D. Spence DP Cardinali (2007-01-01; backlinks)

“”, Stephanie 2005

2005-bellipanni.pdf: “”⁠, Stephanie (2005-01-01; backlinks)

“Low, but Not High, Doses of Melatonin Entrained a Free-running Blind Person With a Long Circadian Period”, Lewy et al 2002

2002-lewy.pdf: “Low, but not high, doses of melatonin entrained a free-running blind person with a long circadian period”⁠, Alfred J. Lewy, Jonathan S. Emens, Robert L. Sack, Brant P. Hasler, Rebecca A. Bernert (2002-02-28; similar):

In a previous report, we were unable to entrain one out of seven totally blind people with free-running endogenous melatonin rhythms to 10 mg of exogenous melatonin. This person had the longest circadian period (24.9 h) of the group. We now find that this person can be entrained to 0.5 mg of melatonin, but not to 20 mg. These results are consistent with the idea that too much melatonin may spill over onto the wrong zone of the melatonin phase-response curve.

[Keywords: circadian rhythms, free-running totally blind people, melatonin, melatonin phase-response curve]

“Melatonin in Sleep Disorders and Jet-lag”, Cardinali et al 2002

2002-cardinali.pdf: “Melatonin in sleep disorders and jet-lag”⁠, Daniel P. Cardinali, Luis I. Brusco, Santiago Pérez Lloret, Analía M. Furio (2002; backlinks; similar):

In elderly insomniacs, melatonin treatment decreased sleep latency and increased sleep efficiency. This is particularly marked in Alzheimer’s disease (AD) patients. Melatonin is effective to reduce substantially benzodiazepine use. In addition, melatonin administration synchronizes the sleep-wake cycle in blind people and in individuals suffering from delayed sleep phase syndrome or jet lag. Urinary levels of 6-sulphatoxymelatonin decrease with age and in chronic diseases like AD or coronary heart disease. The effect of melatonin on sleep is probably the consequence of increasing sleep propensity (by inducing a fall in body temperature) and of a synchronizing effect on the circadian clock (chronobiotic effect).

“Melatonin in Psychiatric Disorders: A Review on the Melatonin Involvement in Psychiatry”, Pacchierotti & C. 2001

2001-pacchierotti.pdf: “Melatonin in Psychiatric Disorders: A Review on the Melatonin Involvement in Psychiatry”⁠, Pacchierotti, C. (2001-01-01; backlinks)

“The Impact of Sleep Deprivation on Decision Making: A Review”, Harrison & Horne 2000

2000-harrison.pdf: “The Impact of Sleep Deprivation on Decision Making: A Review”⁠, Yvonne Harrison, James A. Horne (2000-09-01; ⁠, ; backlinks; similar):

Few sleep deprivation (SD) studies involve realism or high-level decision making, factors relevant to managers, military commanders, and so forth, who are undergoing prolonged work during crises. Instead, research has favored simple tasks sensitive to SD mostly because of their dull monotony. In contrast, complex rule-based, convergent, and logical tasks are unaffected by short-term SD, seemingly because of heightened participant interest and compensatory effort.

However, recent findings show that despite this effort, SD still impairs decision making involving the unexpected, innovation, revising plans, competing distraction, and effective communication. Decision-making models developed outside SD provide useful perspectives on these latter effects, as does a neuropsychological explanation of sleep function.

SD presents particular difficulties for sleep-deprived decision makers who require these latter skills during emergency situations.

“The Effect of Melatonin Administration on Pituitary Hormone Secretion in Man”, MIN 1999

1999-forsling.pdf: “The effect of melatonin administration on pituitary hormone secretion in man”⁠, A D. MIN (1999-01-01; backlinks)

“Effect of Sustained Nocturnal Transbuccal Melatonin Administration on Sleep and Temperature in Elderly Insomniacs”, Dawson et al 1998

1998-dawson.pdf: “Effect of Sustained Nocturnal Transbuccal Melatonin Administration on Sleep and Temperature in Elderly Insomniacs”⁠, Drew Dawson, Naomi L. Rogers, Cameron J. van den Heuvel, David J. Kennaway, Kurt Lushington (1998-12-01; similar):

Previous research has suggested a role for the pineal hormone melatonin in the control of the body’s sleep-wake and thermoregulatory systems. In the elderly population, there have been reports of decreased nighttime secretion of melatonin and suggestions that this may, in turn, be responsible for the increased incidence of sleep disorders reported by this age group. On this basis, it has been suggested that augmented nocturnal melatonin levels may improve sleep quality in age-related sleep disorders. Following screening assessments, 12 elderly (> 55 years) subjects with sleep maintenance insomnia were treated with either 0.5 mg transbuccal melatonin or a placebo for two sessions of 4 consecutive nights, at least 3 days apart. Subjects self-selected lights-out times, and sleep was assessed using standard polysomnographic (PSG) measures. Body temperature was measured continually from 2100 to 0700 h, and sleep quality was assessed from PSG variables measured. Nightly urine samples were assayed for the melatonin metabolite 6-sulfatoxy-melatonin (aMT.6S). Compared to the placebo, transbuccal melatonin administration significantly increased mean nocturnal aMT.6S excretion (mean ± SEM: 194.2 ± 16.5 vs. 42.5 ± 7.7 nmol). In addition, there was a significant reduction in core body temperature relative to the placebo condition (p < .05). However, sustained transbuccal melatonin treatment had no positive statistically-significant effect on any PSG measure of sleep quality. The results from the present study suggest that sustained nocturnal administration of melatonin, in the low pharmacological range, might be of limited clinical benefit in this subject population.

“Multivitamin Use, Folate, and Colon Cancer in Women in the Nurses' Health Study”, Giovannucci et al 1998

1998-giovannucci.pdf: “Multivitamin Use, Folate, and Colon Cancer in Women in the Nurses' Health Study”⁠, Edward Giovannucci, Meir J. Stampfer, Graham A. Colditz, David J. Hunter, Charles Fuchs, Bernard A. Rosner et al (1998-10-10; ; backlinks; similar):

Background: High intake of folate may reduce risk for colon cancer⁠, but the dosage and duration relations and the impact of dietary compared with supplementary sources are not well understood.

Objective: To evaluate the relation between folate intake and incidence of colon cancer.

Design: Prospective cohort study.

Setting: 88 756 women from the Nurses’ Health Study who were free of cancer in 1980 and provided updated assessments of diet, including multivitamin supplement use, from 1980 to 1994.

Patients: 442 women with new cases of colon cancer.

Measurements: Multivariate relative risk (RR) and 95% CIs for colon cancer in relation to energy-adjusted folate intake.

Results: Higher energy-adjusted folate intake in 1980 was related to a lower risk for colon cancer (RR, 0.69 [95% CI, 0.52 to 0.93] for intake >400 µg/​d compared with intake ≤ 200 µg/​d) after controlling for age; family history of colorectal cancer; aspirin use; smoking; body mass; physical activity; and intakes of red meat, alcohol, methionine, and fiber. When intake of vitamins A, C, D, and E and intake of calcium were also controlled for, results were similar. Women who used multivitamins containing folic acid had no benefit with respect to colon cancer after 4 years of use (RR, 1.02) and had only nonsignificant risk reductions after 5 to 9 (RR, 0.83) or 10 to 14 years of use (RR, 0.80). After 15 years of use, however, risk was markedly lower (RR, 0.25 [CI, 0.13 to 0.51]), representing 15 instead of 68 new cases of colon cancer per 10 000 women 55 to 69 years of age. Folate from dietary sources alone was related to a modest reduction in risk for colon cancer, and the benefit of long-term multivitamin use was present across all levels of dietary intakes.

Conclusions: Long-term use of multivitamins may substantially reduce risk for colon cancer. This effect may be related to the folic acid contained in multivitamins.

“Melatonin for the Treatment of Sleep Disturbances in Major Depressive Disorder”, Dolberg et al 1998

“Melatonin for the Treatment of Sleep Disturbances in Major Depressive Disorder”⁠, Ornah T. Dolberg, Schmuel Hirschmann, Leon Grunhaus (1998-08-01; ; backlinks; similar):

Objective: The authors’ goal was to examine the hypnotic effects of slow-release melatonin during the initial 4 weeks of treatment with fluoxetine in 19 patients with major depressive disorder.

Method: 24 outpatients with major depressive disorder were included in the study; 19 completed the study. 10 patients were treated with fluoxetine plus slow-release melatonin and 9 were given fluoxetine plus placebo in a double-blind protocol for 4 weeks. Response was assessed by using rating scales for depression and sleep.

Results: The 10 patients given slow-release melatonin reported statistically-significantly better scores on the Pittsburgh Sleep Quality Index (PSQI) than the 9 patients given placebo. No statistically-significant differences in the rate of improvement in depressive symptoms were noted between the 2 groups. No particular side effects were noted from the combination of fluoxetine and slow-release melatonin.

Conclusions: Slow-release melatonin was effective in improving the sleep of patients with major depressive disorder. Slow-release melatonin had no effect on the rate of improvement in symptoms of major depressive disorder. The authors conclude that the role of slow-release melatonin for sleep disturbances in major depressive disorder should be investigated further.

“Nocturnal Serum Melatonin Profile in Major Depression in Children and Adolescents”, Shafii et al 1996

1996-shafii.pdf: “Nocturnal Serum Melatonin Profile in Major Depression in Children and Adolescents”⁠, Mohammad Shafii, Duncan R. MacMillan, Mary P. Key, Ann McCue Derrick, Nancy Kaufman, Irwin D. Nahinsky et al (1996-11-01; backlinks; similar):

Background: In major depression, biological rhythm disturbances in sleep, appetite, and mood suggest dysregulation in neuroendocrine functions, possibly in the pineal gland. In this study, pineal gland function was examined by measuring nocturnal serum melatonin levels during both wakefulness and sleep in depressed children and adolescents.

Methods: 22 youths aged 8 to 17 years primarily with major depression were compared with 19 controls. Blood samples were drawn every half hour from 6 PM to 7 AM. Nocturnal serum melatonin levels were measured by radioimmunoassay.

Results: The overall nocturnal serum melatonin profile from 6 PM to 7 AM was statistically-significantly higher (mean±SD, 0.18±0.14nmol/​L) in the depressed group than in the controls [mean±SD, 0.15±0.10 nmol/​L, F(1,26) = 4.37, p < 0.05]. In dim light, when the subjects were awake, no difference existed between the 2 groups. After lights-out, from 10 PM to 7 AM, the melatonin profile rose in both groups; however, the depressed group had a statistically-significantly higher increase (mean±SD,0.24±0.14nmol/​L) than the controls [mean±SD,0.18±0.07nmol/​L, F(1,26) = 4.93, mean square error = 0.11, p = 0.04]. Post hoc analysis showed a statistically-significantly higher melatonin profile in depressed subjects without psychosis (n = 15) than in depressed subjects with psychosis (n = 7) or in the controls.

Conclusions: Measuring the overall nocturnal serum melatonin profile during darkness may help to differentiate children and adolescents with major depression without psychosis from those with psychosis and from controls.

“The Role of Deliberate Practice in the Acquisition of Expert Performance”, Ericsson et al 1993

1993-ericsson.pdf: “The role of deliberate practice in the acquisition of expert performance”⁠, K. Anders Ericsson, Ralf T. Krampe, Clemens Tesch-Römer (1993-07; ⁠, ; backlinks; similar):

The theoretical framework presented in this article explains expert performance as the end result of individuals’ prolonged efforts to improve performance while negotiating motivational and external constraints. In most domains of expertise, individuals begin in their childhood a regimen of effortful activities (deliberate practice) designed to optimize improvement. Individual differences, even among elite performers, are closely related to assessed amounts of deliberate practice. Many characteristics once believed to reflect innate talent are actually the result of intense practice extended for a minimum of 10 years. Analysis of expert performance provides unique evidence on the potential and limits of extreme environmental adaptation and learning.

“Differences in Nocturnal Melatonin Secretion between Melancholic Depressed Patients and Control Subjects”, Brown et al 1985

1985-brown.pdf: “Differences in nocturnal melatonin secretion between melancholic depressed patients and control subjects”⁠, Richard Brown, James H. Kocsis, Stanley Caroff, Jay Amsterdam, Andrew Winokur, Peter E. Stokes, Alan Frazer et al (1985-07; ; backlinks):

The authors took multiple serum samples for measurement of melatonin between 4:30PM and 7:30AM in 7 male depressed patients with melancholia and 5 healthy male control subjects and found that:

melancholic patients had a statistically-significantly lower rise of melatonin. They also compared a second, separate group of 14 women and 5 men suffering from melancholic depression with 7 healthy male control subjects and 9 depressed women without melancholia. The melancholic patients had a statistically-significantly lower concentration of serum melatonin at 11:00PM than either the control subjects or the non-melancholic depressed patients.

These findings support the possibility that the functioning of the pineal gland is altered in these patients.