Chronobiol Int. 2009 Dec;26(8):1602-12. Amber lenses to block blue light and improve sleep: a randomized trial.

Burkhart K, Phelps JR. University of Toledo, Ohio, USA. All light is not equal: blue wavelengths are the most potent portion of the visible electromagnetic spectrum for circadian regulation. Therefore, blocking blue light could create a form of physiologic darkness. Because the timing and quantity of light and darkness both affect sleep, evening use of amber lenses to block blue light might affect sleep quality. Mood is also affected by light and sleep; therefore, mood might be affected by blue light blockade. In this study, 20 adult volunteers were randomized to wear either blue-blocking (amber) or yellow-tinted (blocking ultraviolet only) safety glasses for 3 h prior to sleep. Participants completed sleep diaries during a one-week baseline assessment and two weeks' use of glasses. Outcome measures were subjective: change in overall sleep quality and positive/negative affect. Results demonstrated that sleep quality at study outset was poorer in the amber lens than the control group. Two- by threeway ANOVA revealed significant (p < .001) interaction between quality of sleep over the three weeks and experimental condition. At the end of the study, the amber lens group experienced significant (p < .001) improvement in sleep quality relative to the control group and positive affect (p = .005). Mood also improved significantly relative to controls. A replication with more detailed data on the subjects' circadian baseline and objective outcome measures is warranted. ------J Biol Rhythms. 2008 Oct;23(5):379-86. Sensitivity of the human circadian system to short-wavelength (420-nm) light. Brainard GC, Sliney D, Hanifin JP, Glickman G, Byrne B, Greeson JM, Jasser S, Gerner E, Rollag MD. Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, USA. george.brainard@jefferson.edu The circadian and neurobehavioral effects of light are primarily mediated by a retinal ganglion cell photoreceptor in the mammalian eye containing the

photopigment melanopsin. Nine action spectrum studies using rodents, monkeys, and humans for these responses indicate peak sensitivities in the blue region of the visible spectrum ranging from 459 to 484 nm, with some disagreement in short-wavelength sensitivity of the spectrum. The aim of this work was to quantify the sensitivity of human volunteers to monochromatic 420-nm light for plasma melatonin suppression. Adult female (n=14) and male (n=12) subjects participated in 2 studies, each employing a within-subjects design. In a fluence-response study, subjects (n=8) were tested with 8 light irradiances at 420 nm ranging over a 4-log unit photon density range of 10(10) to 10(14) photons/cm(2)/sec and 1 dark exposure control night. In the other study, subjects (n=18) completed an experiment comparing melatonin suppression with equal photon doses (1.21 x 10(13) photons/cm(2)/sec) of 420 nm and 460 nm monochromatic light and a dark exposure control night. The first study demonstrated a clear fluence-response relationship between 420-nm light and melatonin suppression (p<0.001) with a halfsaturation constant of 2.74 x 10(11) photons/cm(2)/sec. The second study showed that 460-nm light is significantly stronger than 420-nm light for suppressing melatonin (p<0.04). Together, the results clarify the visible short-wavelength sensitivity of the human melatonin suppression action spectrum. This basic physiological finding may be useful for optimizing lighting for therapeutic and other applications. ------Med Hypotheses. 2009 Sep;73(3):324-5. Epub 2009 Apr 16. Nighttime use of special spectacles or light bulbs that block blue light may reduce the risk of cancer. Alpert M, Carome E, Kubulins V, Hansler R. Lighting Innovations Institute, John Carroll University, 20700 North Park Blvd., University Heights, OH 44118, USA. For more than 15 years evidence has been accumulating that there is a link between a lack of melatonin and cancer, especially breast, ovarian and prostate cancer. For a similar period it has been known that exposing the eyes to light when melatonin is normally flowing reduces or eliminates the flow. What is relatively new is that it is primarily the blue wavelengths that are responsible for loss of melatonin. Blocking these blue rays with amber glasses restores melatonin flow. Also

new is the direct evidence, from analysis of the famous nurses' health study, that having more melatonin present in first morning urine is linked to a reduction in the incidence of breast cancer. This leads to the hypothesis that wearing amber glasses (or using blue-free light bulbs) for a few hours before bedtime maximizes melatonin production and reduces the risk of breast, ovarian and prostate cancer and possibly other cancers. -----Oncol Nurs Forum. 2009 Nov;36(6):723-31. Factors associated with sleep-wake disturbances in child and adult survivors of pediatric brain tumors: a review. Gapstur R, Gross CR, Ness K. School of Nursing, University of Minnesota, Minneapolis, USA. rgapstur@emer-phys.com PURPOSE/OBJECTIVES: To identify factors associated with sleep-wake disturbances in pediatric and adult survivors (aged older than 18 years) of pediatric brain tumors. DATA SOURCES: A computerized literature search was completed using MEDLINE, CINAHL, CancerLit, Dissertation Abstracts International, and PsycINFO. The search and a personal communication with one author discovered 25 English-language research articles and case reports describing sleep-wake patterns in brain tumor survivors from 19662008. DATA SYNTHESIS: Disease- and treatment-related factors from direct injury to the hypothalamus results in irregular melatonin secretion and low hypocretin levels. This contributes to decreased daytime alertness, which remains the most reported sleep-wake disturbance in brain tumor survivors. Patients with craniopharyngiomas, radiation dose more than 3,500 cGy, and younger age at time of treatment experienced more severe sleep dysfunction. CONCLUSIONS: Patients with brain tumors experience a disruption of sleep-wake patterns associated with major dysfunction in the hypothalamic-pituitary axis, affecting both Process S (homeostasis) and Process C (circadian) from the Two-Process Model of Sleep Regulation. Various demographic-, disease-, and treatment-related variables are involved in driving the onset of sleep disturbances. Interventions are needed to improve daytime function and decrease the effect of sleep disturbances on quality of life. IMPLICATIONS FOR NURSING: Current sleep literature has identified patterns of sleep disturbances in cross-sectional studies of brain tumor survivors. Rigorous

longitudinal designs are needed for future studies to detect onset patterns and trajectory of sleep-wake disorders. Intervention studies are needed to impact excessive daytime sleepiness, irregular sleeping and waking patterns, and other identified sleep-wake disorders. -----http://www.psycheducation.org/depression/darkrx.htm Dark Therapy (updated 8/2006) [Update 2/2005: For at least 3 years this idea was based on two cases. That's it, two cases. Finally an Italian research team has studied the same approach in 32 patients, again finding it works. You'll find the details from that study at the bottom of this page, and some links for much more information on the role of light and dark in bipolar treatment.] This will take a little explaining, and then we'll come around to the treatment issue. First, here's a story from the great research team at the National Institutes of Mental Health (NIMH), originally reported in Bipolar Network News from which the graphic below derives; later published by Wehr and colleagues. Here you see a 3 year record of sleep and mood for a man with rapidcycling bipolar disorder. How the NIMH managed to get these recordings I don't know. On the left, marked by red, you see a sleep record (don't bother trying to figure out what it means, just look at the pattern, which will be obvious in a minute). Next to it, marked by purple, is the total amount of sleep per 24 hours (to the right is a lot, to the left is a little -- again, it's the pattern that matters). On the right, marked by blue, you see a mood record that shows obvious and frequent cycling from manic peaks to depressive lows (the lows are slightly longer, you can see, especially the one marked ***). If you look closely you can see that the amount of sleep (under the purple arrow) closely matches the mood curve: less sleep during + peaks; and more sleep during the depressive phases.

The main point so far is to see the rapid and obvious cycling. Here is the same record, starting from the severe depressive episode marked before (***), and now continuing into treatment -- beginning at *. Notice that almost as soon as treatment begins, his sleep becomes more organized (neat black and gray bands); his total sleep per 24 hours starts to be consistent *; and his mood curve starts to settle toward the middle *. So, what was this treatment? NO MEDICATIONS. That sounds great, doesn't it? But it wasn't easy: the NIMH research team required this man to stay in darkness 14 hours every night, from 6 pm to 8 am the next morning. (After a few weeks they eased up: only 10 hours of "enforced darkness"). How could "darkness" treat rapid cycling? And what does this mean for your treatment? How does darkness treat rapid cycling? To understand this patient's response to this treatment, we must turn to our "biological clock". For a stunning example of how powerful this clock is, and how important in bipolar disorder, have a look at an example of a patient who cycled every 24 hours, first a day up, then a day down -- and has matching laboratory evidence of cycling (hormones, even handwriting!) The NIMH team theorized that in rapid cyclers, their clocks have lost the ability to respond to the timing of natural day and night. They knew that the a specific part of the hypothalamus, the suprachiasmatic nucleus (SCN), has direct nerve connections from the eyes. It gets direct signals about how much light is out there. And it has been shown to be the main location of the "biological clock" in many animals, including humans. They thought that the SCN might get "desensitized" in some susceptible people by too much light, namely too much artificial light at night. (For much more information on how light and darkness affect bipolar disorder through the biological clock, start with my page on Bipolar Disorder: Light and Darkness (2006), and try some of the links there as well -- cool stuff!)

They hoped that the could reverse this with its opposite -- enforced darkness at night. They believed that the SCN could become more sensitive again, if given this treatment. Perhaps then it would then have more influence over the body's cycling, as it is supposed to? They set out to test this idea by taking a person with rapid cycling, on no medications, and helping him get "plenty of dark". In fact, they made sure that's what he got! Every night he came to their research program and went into a room with a bed, but no lights. He didn't have to sleep, but he couldn't do anything -- there was no light to read by, no television, no phone: "enforced bed rest and darkness". You can see how well this worked for him from the curves above. What does this mean for your treatment? I hope the implications are obvious: you might be able to get by with less medication if you avoid late evening light and activity. Unfortunately, because there is no pharmaceutical manufacturer selling "darkness", we don't have lots of funding to support research on this treatment. So there have not been formal tests of this approach, except a second case report, and that Italian study, details below. On the other hand, here's one treatment that has very few risks (the other is exercise, if you haven't read about that yet). And it would be easy to move at least a little bit in the direction of less artificial light, and less late evening activity. At worst, you'd spend some evenings lying there in the dark. I know from my patients' reports that this is not trivial: it means lying there with your thoughts, which can be pretty rough. However, look at this guy's curves again -- he did it, and look how fast things started changing for him (on no medications): I don't recommend that you try to treat yourself with darkness alone, that's not the point; rather, I suggest that you look at how much artificial light you're getting, particularly late at night, and try to cut back on that. There is indirect evidence that blue light is the particular type of light you need to avoid at night (unfortunately, just like the kind of light your TV puts out).

several manufacturers are making low-blue-light products which might be of use -- at least a low-blue nightlight, if not a filter for your TV! See more in the Bipolar Disorder: Light and Darkness essay. That Italian study of 32 patients used dark therapy (6 pm to 8 am) for only three nights, and still they were able to show that it was better than "treatment as usual".Barbini That's the good news. The bad news is that it only seemed to work if the patient had been in a manic phase for a relatively short period of time. You see, the group of patients they studied did not have the "rapid cycling" pattern shown above, but rather a manic episode that was severe enough to require hospitalization. On the other hand, one could interpret this as more good news, I suppose, in that dark therapy was able to help even the most extreme form of bipolar manic symptoms, and do it in three days! Patients who received dark therapy required less medication and left the hospital earlier. Note however that these patients were still getting the usual medication approaches, unlike the patient described above. With the addition of the Italian data, and since the risks of this treatment are minimal except for the utter boredom it surely inflicts, which I understand is not trivial, I think it's time to consider adding "dark therapy" for manic phases and rapid cycling. At minimum we can presume, for now, that avoiding late nights in front of a TV or computer screen (or working graveyard shifts) is likely to help minimize the need for medication and possibly enable a speedier recovery. If avoiding such light is impossible, learn about blue-light blocking (which has not yet been directly tested but follows the research in this area). -----J Psychiatr Res. 2010 Jan;44(2):69-74. Epub 2009 Dec 11. A pilot study of the phase angle between cortisol and melatonin in major depression - a potential biomarker? Buckley TM, Schatzberg AF. Dept. of Psychiatry and Behavioral Sciences, Stanford University Medical School, 401 Quarry Road, Stanford, CA 94305-5730, United States. tbuckley@stanfordalumni.org INTRODUCTION: Hypothalamic-pituitary-adrenal (HPA) axis and melatonin

rhythm alterations have been independently reported in major depression (MDD) as well as in insomnia. In this pilot study, we link cortisol and melatonin rhythms and propose that the phase angle between cortisol acrophase (CA) and dim-light melatonin onset (20 pg/ml) (DLMO-20) may yield a useful state specific biomarker for MDD. METHODS: Six healthy (HC) and six depressed (MDD) psychotropic free subjects were admitted to the General Clinical Research Center. Blood was sampled for cortisol and melatonin from 1600h to 1000h, under dim lights (<20lux) and constant routine. Time for DLMO-20 and peak cortisol concentration was determined for each subject. Phase angle was computed as the difference in time between CA and DLMO-20. RESULTS: Phase angle was significantly increased in MDD's versus HC's (13.40+/-1.61h. versus 11.61+/-1.66h, p=0.026). Using ROC analysis, a phase angle greater than 13.57h distinguished MDD's from HC's (sensitivity=0.83, specificity=1.0). Mean nocturnal melatonin (1600-1000h) was significantly decreased in MDD's versus HC's (22.67+/-9.08 pg/ml versus 47.82+/-14.76 pg/ml, p=0.015). CONCLUSIONS: The phase angle between CA and DLMO-20 appears to distinguish HC's from MDD's and may be a useful biomarker to aid biologic assessment as well as treatment. Lower nocturnal melatonin in MDD's highlights its importance in MDD's pathophysiology. Additional study with larger sample size is needed to confirm the results of this pilot study. The mechanism for this phase angle difference and decreased melatonin, itself, requires further study. Copyright 2009. Published by Elsevier Ltd. -----Chronobiol Int. 2003 Jan;20(1):123-33. Effects of dim or bright-light exposure during the daytime on human gastrointestinal activity. Sone Y, Hyun KJ, Nishimura S, Lee YA, Tokura H. Department of Food and Nutrition, Faculty of Science of Living, Osaka City University, Osaka, Japan. sone@life.osaka-cu.ac.jp On the basis of our previous findings that bright-light exposure during the daytime has profound influence on physiological parameters such as melatonin secretion and tympanic temperature in humans, we proposed the hypothesis that bright vs. dim light-exposure during the daytime has a different influence on the activity of the digestive system via the endocrine and/or autonomic nervous system. To examine this hypothesis, we

conducted a series of counterbalanced experiments in which subjects stayed the daytime (7:00 to 15:00h) under either a dim (80 lux) or bright (5,000 lux) light condition. We measured gastrointestinal activity using a breath hydrogen (indicative of carbohydrate malabsorption) and an electrogastrography (EGG, indicative of gastric myoelectric activity) test. The results showed the postprandial breath hydrogen excretion during the following nighttime period after daytime exposure to the dim-light condition was significantly higher than under the bright-light condition (p < 0.05). In addition, the spectrum total power of the EGG recorded after taking the evening meal was significantly lower for the dim than bright-light condition (p < 0.05). These results support our hypothesis and indicate that dimlight exposure during the daytime suppresses the digestion of the evening meal, resulting in malabsorption of dietary carbohydrates in it. -------Dig Dis Sci. 2000 Jul;45(7):1255-9. Carbohydrate malabsorption syndromes and early signs of mental depression in females. Ledochowski M, Widner B, Sperner-Unterweger B, Propst T, Vogel W, Fuchs D. Department of Clinical Nutrition, Institute of Medical Chemistry and Biochemistry, University of Innsbruck, Austria. Fructose and lactose malabsorption are characterized by impaired duodenal fructose transport or by the deficiency of mucosal lactase, respectively. As a consequence, the nonabsorbed saccharides reach the colon, where they are broken down by bacteria to short fatty acids, CO2, and H2. Bloating, cramps, osmotic diarrhea, and other symptoms of irritable bowel syndrome are the consequence and can be seen in about 50% of carbohydrate malabsorbers. We have previously shown that fructose as well as lactose malabsorption were associated with signs of mental depression. It was therefore of interest to investigate possible interactions between fructose and lactose malabsorption and their influence on the development of signs of depression. In all, 111 otherwise healthy volunteers (81 females and 30 males) with gastrointestinal complaints were analyzed by measuring breath H2 concentrations after an oral dose of 50 g lactose and of 50 g fructose one week apart. They were

classified as normals, isolated fructose malabsorbers, isolated lactose malabsorbers, and combined fructose/lactose malabsorbers. All patients filled out a Beck's depression inventory-questionnaire. Twenty-five individuals (22.5%) were neither fructose nor lactose malabsorbers (group 1), 69 (62.2%) were only fructose malabsorbers (group 2), 4 (3.6%) were only lactose malabsorbers (group 3), and 13 (11.7%) presented with fructose and lactose malabsorption together (group 4). Isolated fructose malabsorption and combined fructose/lactose malabsorption was significantly associated with a higher Beck's depression score. Further analysis of the data show that this association was strong in females (P < 0.01), but there was no such association between carbohydrate malabsorption and early signs of depression in males. In conclusion, the data confirm that fructose malabsorption may play a role in the development of mental depression in females and additional lactose malabsorption seems to further increase the risk for development of mental depression. -----J Biol Rhythms. 1997 Dec;12(6):568-74. Acute and delayed effects of exercise on human melatonin secretion. Buxton OM, L'Hermite-Balriaux M, Hirschfeld U, Cauter E. Department of Medicine, University of Chicago, IL 60637, USA. Accumulating evidence suggests that exercise may have both rapid and delayed effects on human melatonin secretion. Indeed, exercise may acutely (i.e., within minutes) alter melatonin levels and result in a shift of the onset of nocturnal melatonin 12 to 24 h later. The presence and nature of both acute and delayed effects appear to be dependent on the timing of exercise. The presence of a detectable acute effect also depends on the duration, intensity, and type of exercise. Late evening exercise during the rising phase of melatonin secretion may blunt melatonin levels. High-intensity exercise during the nighttime period, when melatonin levels already are elevated, consistently results in a further (nearly 50%) elevation of melatonin levels. No effect of low-intensity exercise performed at the same circadian phase could be detected. Irrespective of intensity, exercise near the offset of melatonin secretion or during the daytime has no

consistent acute effect on melatonin secretion. Nighttime exercise, whether of moderate or high intensity, results in phase delays of the melatonin onset on the next evening. In support of the concept that a shift of the melatonin onset on the day after nighttime exercise represents a shift of intrinsic circadian timing is the observation that similar phase shifts (in both direction and magnitude) may be observed simultaneously for the onset of the circadian elevation of thyrotropin secretion. The observation of exercise-induced phase shifts of the onset of melatonin secretion is, therefore, interpreted as evidence that, in humans as in rodents, increased physical activity during the habitual rest period is capable of altering circadian clock function. -----Am J Physiol Regul Integr Comp Physiol. 2003 Mar;284(3):R714-24. Exercise elicits phase shifts and acute alterations of melatonin that vary with circadian phase. Buxton OM, Lee CW, L'Hermite-Baleriaux M, Turek FW, Van Cauter E. Department of Medicine, Section of Endocrinology, University of Chicago, Chicago, IL 60637, USA. orfeu@uchicago.edu To examine the immediate phase-shifting effects of high-intensity exercise of a practical duration (1 h) on human circadian phase, five groups of healthy men 20-30 yr of age participated in studies involving no exercise or exposure to morning, afternoon, evening, or nocturnal exercise. Except during scheduled sleep/dark and exercise periods, subjects remained under modified constant routine conditions allowing a sleep period and including constant posture, knowledge of clock time, and exposure to dim light intensities averaging (+/-SD) 42 +/- 19 lx. The nocturnal onset of plasma melatonin secretion was used as a marker of circadian phase. A phase response curve was used to summarize the phase-shifting effects of exercise as a function of the timing of exercise. A significant effect of time of day on circadian phase shifts was observed (P < 0.004). Over the interval from the melatonin onset before exercise to the first onset after exercise, circadian phase was significantly advanced in the evening exercise group by 30 +/- 15 min (SE) compared with the phase delays observed in the noexercise group (-25 +/- 14 min, P < 0.05). Phase shifts in response to evening exercise exposure were attenuated on the second day after exercise exposure and no longer significantly different from phase shifts

observed in the absence of exercise. Unanticipated transient elevations of melatonin levels were observed in response to nocturnal exercise and in some evening exercise subjects. Taken together with the results from previous studies in humans and diurnal rodents, the current results suggest that 1) a longer duration of exercise exposure and/or repeated daily exposure to exercise may be necessary for reliable phase-shifting of the human circadian system and that 2) early evening exercise of high intensity may induce phase advances relevant for nonphotic entrainment of the human circadian system. ----CNS Drugs. 2001;15(4):311-28. Circadian rhythm sleep disorders: pathophysiology and potential approaches to management. Zisapel N. Department of Neurobiochemistry, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Israel. navazis@ccsg.tau.ac.il An intrinsic body clock residing in the suprachiasmatic nucleus (SCN) within the brain regulates a complex series of rhythms in humans, including sleep/wakefulness. The individual period of the endogenous clock is usually >24 hours and is normally entrained to match the environmental rhythm. Misalignment of the circadian clock with the environmental cycle may result in sleep disorders. Among these are chronic insomnias associated with an endogenous clock which runs slower or faster than the norm [delayed (DSPS) or advanced (ASPS) sleep phase syndrome, or irregular sleep-wake cycle], periodic insomnias due to disturbances in light perception (non-24hour sleep-wake syndrome and sleep disturbances in blind individuals) and temporary insomnias due to social circumstances (jet lag and shift-work sleep disorder). Synthesis of melatonin (N-acetyl-5-methoxytryptamine) within the pineal gland is induced at night, directly regulated by the SCN. Melatonin can relay time-of-day information (signal of darkness) to various organs, including the SCN itself. The phase-shifting effects of melatonin are essentially opposite to those of light. In addition, melatonin facilitates sleep in humans. In the absence of a light-dark cycle, the timing of the circadian clock, including the timing of melatonin production in the pineal gland, may

to some extent be adjusted with properly timed physical exercise. Bright light exposure has been demonstrated as an effective treatment for circadian rhythm sleep disorders. Under conditions of entrainment to the 24-hour cycle, bright light in the early morning and avoidance of light in the evening should produce a phase advance (for treatment of DSPS), whereas bright light in the evening may be effective in delaying the clock (ASPS). Melatonin, given several hours before its endogenous peak at night, effectively advances sleep time in DSPS and adjusts the sleep-wake cycle to 24 hours in blind individuals. In some blind individuals, melatonin appears to fully entrain the clock. Melatonin and light, when properly timed, may also alleviate jet lag. Because of its sleep-promoting effect, melatonin may improve sleep in night-shift workers trying to sleep during the daytime. Melatonin replacement therapy may also provide a rational approach to the treatment of age-related insomnia in the elderly. However, there is currently no melatonin formulation approved for clinical use, neither are there consensus protocols for light or melatonin therapies. The use of bright light or melatonin for circadian rhythm sleep disorders is thus considered exploratory at this stage. -----Superoxide anions (O2(*-)) = a Reactive Oxygen Species, i.e. causes inflammation / is diminished by superoxide dismutase ------http://www.acne.org/messageboard/Zinc-Zinc-Regimen-Adult243340.html&st=80 If you accept the primacy of zinc among supplements for acne, then it's logical to include selenium. The reason is that selenium appears to be key in allowing zinc (the ion) to trade partners from the molecule what brought it to the dance (metallothioneins), to the molecule that is a gunnin' for acne (zinc superoxide dismutase). That's a purely biochemical argument, but there is direct evidence that acne sufferers tend to be low in selenium. Again, selenium may be necessary, but is unlikely to be sufficient. Unlike zinc, the body doesn't defend well against selenium megadosing, and it's unlikely to help much over a more modest dose. 200mcg/day is a defensible dose for fully grown adults. A vitamin B complex pill contains numerous vitamins, and more than one of

them is potentially relevant to acne, and specifically the theory that acne is triggered by the over-active immune system production of superoxide anions to kill the P. acnes bacteria. Taking these four pills (zinc, selenium, vit B complex, vit D) is a way to directly support the manufacture of zinc superoxide dismutase to prevent acne. Unfortunately, you still need superoxide dismutase molecules, and having a normal melatonin cycle is the most effective route to get that. Taking a melatonin pill is unlikely to help (and can even hurt, if you get a big enough dose with the wrong timing). Of the many, many things I have tried (tryptophan pills, melatonin pills, etc.), nothing even comes close to living in bright outdoor light all day followed by regular, long, hard sleep in total darkness. If I could find a way to put that in a pill, I would be off the patent office the very next day, * It's hard to list all the ways melatonin is potentially relevant to acne: it may act as an anti-androgen, it can slow cell division, it can act directly as an anti-oxidant, it instructs cells to crank out more of at least two kinds of anti-oxidant proteins, even some of the downstream metabolites of melatonin can act as anti-oxidants. * I also spent some time studying caffeine because it's interesting how variable its effects can be on acne. After realizing that caffeine can actually slow the breakdown of melatonin, I began to wonder if early morning caffeine is anti-acne (by keeping melatonin levels higher longer) and evening caffeine is pro-acne (by impairing the nightly melatonin surge). * But more: since I believe the root systemic cause is living in dim light that impairs digestion of the tryptophan and zinc needed to manufacture zinc superoxide dismutase, I can (try to!) tie nicotinamide directly to this model of acne. The liver uses up large amounts of tryptophan (60-to-1 ratio by weight) to make nicotinamide, tryptophan that will then be unavailable for creating the melatonin that stimulates cells to create superoxide dismutase. My suspicion is that megadose nicotinamide decreases the amount of tryptophan burned by the liver for making nicotinamide. The actual amount of tryptophan

burned to create 1g of niacin can vary by a factor of 2 between individuals -- another possible factor in the variability of acne severity. * If I live outdoors with my eyes in bright sunlight 12 hours a day, there is no question I can eat the same diet that appears to exacerbate acne if I'm living in dim indoor light. If my experience generalized to others, this is the missing link to explain why diet does -- and doesn't -- affect acne. Live in dim light, and the foods that cause carb malabsorption will generally give you acne (via the long chain of events that starts with not getting enough tryptophan and zinc absorbed through the intestinal walls). Live in bright sunlight, and suddenly "problem" foods may be consumed with no consequences. Most long-term sufferers have experienced inexplicable periods where it seemed like highly reliable "problem" foods suddenly caused no problem; I believe the answer to that mystery is carb malabsorption, and the usual variable that makes the difference is bright light exposure to the eyes (though estrogen modulates pineal production of melatonin, and gives women an extra variable to affect the primary chain of events that produces acne). * Buy the biggest, brightest fluorescents you can (e.g., multiple 4-foot 40watt bulbs) and position them so they are glaring in your eyes when you are sitting at whatever spot you spend the most time sitting indoors. Preferably no more than 4 foot away from your eyeballs. There is a standard for fluorescent bulbs that indicates how close they are to replicating the look of sunlight. You want the highest CRI you can get (should be able to get >= 90) and a temperature around 5500K. * To be clear, the stomach problems may just be the very direct result of carb malabsorption. IOW, the pain and discomfort is just what happens when you eat a problem food out of synch with your melatonin cycle. The acne comes later, because that disturbance in your gut is keeping at least two important nutrients (tryptophan and zinc) from being absorbed -- those two things are needed to make the nightly chemicals that would normally give you enough of the right kind of anti-oxidant in the skin to prevent acne. * I continue to see that a damn big regular dose of lycopene (about 2 cups of tomato sauce, 3 times per week) appears to noticeably reduce oil

production. I never saw such a reduction before while being clear, which reinforces my suspicion that the crux of acne is the generation of superoxide anions, and that the nocturnal surge of pineal melatonin primarily prevents acne by stimulating cells to make superoxide dismutase. Even in studies that show a correlation of increased oil production and acne, you can clearly see that it's nowhere near a linear relationship, which supports the view that the extra oil is not the most direct cause of the lesions. Since I've been able to reproduce acne while taking large doses of lycopene by simply disrupting my sleep (taking big doses of evening caffeine, staying up hours later, etc.), that suggests to me that lycopene, though it may have some ability of it's own to raise superoxide dismutase levels, may primarily affect DHT production. Sort of the complement to melatonin: put them together and you get less oil and increased ability to wipe out the excess superoxide anions that trigger the acne lesion. I can be acne-free without lycopene, but not without the nocturnal melatonin surge. * Carb malabsorption is correlated with lower tryptophan levels, and it may be that the pill form has even more trouble being absorbed in the presence of that problem for some unknown reason. I'm currently trying out a tryptophan precursor (alpha-lactalbumin, bioZzz) but it's in the form of a tasteless powder that I haven't yet found a convenient way to choke down on a regular basis. I recall (but can no longer find) a study in which they gave a breakfast milkshake containing some form of typtophan or precursor to carb malabsorbers, and were able to measure cognitive improvements by afternoon, which makes me think it must be possible to get it through the gut and into the brain (to make serotonin, in the case of that particular experiment). But direct Ltryptophan supplementation just didn't seem to make a dent for me. * AFAIK, taking zinc causes the intestines to "mucus up", as part of the first line of enforcement the body has for tightly regulating zinc levels. The more zinc you swallow, the less gets across the gut lining into the bloodstream. So, another reason to take it on an empty stomach at bedtime is that then you reduce the ability of the zinc to keep other things from being digested.

* For myself, I can say two things about a regular, large dose of lycopene. First, it clearly reduces oil production. Second, it clearly does not prevent acne all by itself. This is consistent with my overall theory. You need both zinc and superoxide dismutase to avoid acne. Living in dim light makes it hard to absorb enough zinc, even if a massive dose of lycopene can help elevate superoxide dismutase levels. Decreasing oil may provide marginal decreases in acne, but it's not getting at the root cause, which (IMO) is the immune system's overreaction to contact with the P. acnes bacteria (in direct contrast to all the folks who think they need a "stronger" immune system to get rid of acne). IMO, acne is reasonably characterized as an auto-immune disease; it's not a failure of the immune system causing the problem, it's a failure of the mechanisms (anti-oxidant levels in this case) that dampen the immune system response. * Does fructose malabsorption interfere with zinc absorption (as it does with tryptophan)? So far, the evidence suggests it does. * What is your sleep actually like? Do you get really sleepy at bedtime and wake up without an alarm clock feeling totally alert and rested, no yawning at all? Toss and turn, or sleep like a log? With no easy way to actually measure the nocturnal melatonin surge, about all you can do is infer it from the quality of your sleep. * I don't have to take any zinc if I'm in bright light all day; if not, though, then I take a 50mg zinc pill at night if I want to stay acnefree. To cover other possible deficiencies relevant to acne, I would also always take a B complex pill like this one. There are a number of different brands with that exact formulation, so I suspect they all come from a single manufacturer. Multiple things in the B complex could be relevant to acne, but certainly one of them is to keep the body from burning up tryptophan to manufacture niacin (you want tryptophan to go to

the brain so it can make serotonin and melatonin). Finally, unless you munch Brazil nuts every day (in which case you have to worry about overdose!) it's hard to guess whether you get enough selenium in your diet or not. In any case, few doctors would get upset at the idea of taking 200mcg per day (make sure you're not already taking a multivitamin that has that much in it). If you can afford the pills, you might also want to swallow some alpha lipoic acid pills. I speculate they can help elevate superoxide dismutase levels (one of the key anti-acne actions of melatonin), and may work better when there's exercise going on. * If money is no object, you might want to try the Big Bag of Pills approach. I've been running this experiment for about a week. Too soon to get excited, but I will say I am cautiously optimistic that it is possible to elevate ZSOD levels enough to treat acne by just slamming down enough of the right pills (in lieu of knowing which pills are "right", I'm of course "throwing the book at it"). * This is all about light in the eyes. In the last decade, a brand new type of cell was discovered in the eye. It is the cell that tells the brain whether it is day or night. It is not used for vision. It responds to intensity, and it responds very slowly (e.g., taking 30 seconds to "trigger", rather than responding to light in a fraction of a second like more well-known cells in the retina). It is most sensitive in the blue area of the spectrum, which is why I use a bulb like the GE Chroma 50 (although any bulb with a CRI >= 89 and a "temperature" of about 5500K should do about as well). * I just live with bright outdoor light in my eyes all day (no sunglasses, no hats) and sleep 9-10 hours in total darkness at the same time each night, every day of the week -- like the 100% acne-free Trobriand Islanders. This eliminates carbohydrate malabsorption so that zinc and tryptophan can actually get absorbed and produces the large nightly melatonin surge we were designed to get that dampens the over-active immune system production of superoxide anions that causes acne.

If I can't do that, then diet suddenly can greatly affect my acne. Living in dim light significantly increases carb malabsorption, so then I have to avoid foods that contain more fructose molecules than glucose (most modern fruits, especially apples, have been bred to be highfructose fruits). Google "FODMAP database" for the type of diets that can help avoid carb malabsorption. I try to eat more tryptophan-containing meat (tryptophan being required to make melatonin) and space it away from carbs. And then I also have to take a Vitamin B complex and zinc, the former being relevant to making melatonin, the latter has more trouble getting digested when you have carb malabsorption. I can reliably start/stop acne production within about 48 hours, which is about the grace period one gets after normalizing a melatonin cycle.