Where does melatonin come from, and do screens block it?

The texts shown during the animation, to read without it.

1. By day, light talks to the clock
   At the back of the eye, a few retinal cells are not used for seeing. They contain a pigment, melanopsin, most sensitive to blue light (peak at 479 nm). They send “it’s daytime” to the brain clock, the suprachiasmatic nucleus, which sits just above the crossing of the optic nerves (Berson, 2002; Bailes and Lucas, 2013).
2. A long detour through the neck
   The clock does not talk directly to the pineal gland, even though it is close by. The whole route is made of nerves: a nearby relay (the paraventricular nucleus), the spinal cord down to the upper chest, a relay in the neck (the superior cervical ganglion), then fibers that climb back along the arteries to the gland. By day, the clock holds back the first relay with a messenger, GABA, and the whole route stays almost silent (Moore, 1996).
3. In the evening, the brake comes off
   When light fades, the clock releases the brake and an electrical impulse travels along the nerves. Norepinephrine does not travel along the route: it is released only at the end, by the fibers coming from the neck, onto the pineal gland. It binds to the beta receptors of its cells, which start their production line. In someone who goes to bed at 11 p.m., this begins around 9 p.m. (Klein, 2007).
4. From tryptophan to melatonin
   The gland starts from tryptophan, a building block of protein that comes from food, and turns it into serotonin. An enzyme, AANAT, then attaches a small group to serotonin: this is the deciding step, and this enzyme works almost only at night: in rats, its activity rises 10 to 100 times. A last enzyme finishes the melatonin (Klein, 1972; Klein, 2007).
5. Nothing is stored
   The gland keeps no reserve: melatonin crosses membranes and leaves as soon as it is made, into the blood and into the fluid around the brain. So the blood level follows production almost minute by minute. It peaks between 2 and 4 a.m., at about 80 to 120 pg/mL in adults, compared with 10 to 20 during the day (Amaral and Cipolla-Neto, 2018; Yu, 2016; Claustrat, 2005).
6. Receptors all over the body
   Melatonin acts on two receptors, MT1 and MT2, sitting on cells: switches, not stores. In the clock, they confirm “it’s night.” In the small blood vessels of the hands and feet, they open them: heat escapes and the body’s core cools slightly, which goes along with falling asleep. There are also some in the retina and the pancreas (Levoye, 2006; Kräuchi, 1997; Lyssenko, 2009).
7. A bright light in the middle of the night
   If a bright light comes on at 3 a.m., the clock puts the brake back on: norepinephrine stops and the enzyme AANAT is destroyed (in rats, half of its activity is gone in about 3 minutes). Since nothing is stored, blood melatonin drops right away, at the pace at which the liver clears it: half in about 45 minutes, from 28 to 126 minutes depending on the person (Gastel, 1998; Harpsøe, 2015).
8. In the morning, the liver cleans up
   With morning light, production stops. The liver breaks down the remaining melatonin (with the enzyme CYP1A2), then the kidneys pass the product into the urine: 6-sulfatoxymelatonin. This is what is measured in morning urine to find out how much was made during the night (Claustrat, 2005).

1. A candle one meter away gives roughly 1 lux. Researchers have proposed staying under 10 lux at the eye in the 3 hours before bedtime, and under 1 lux during sleep (Brown, 2022).
2. Dim light of 10 lux is already enough to shift melatonin a little: in 55 adults, it arrived 22 minutes later at 10 lux, 77 minutes at 30 lux and 109 minutes at 50 lux (Phillips, 2019).
3. In Chang’s study (2015), a tablet at maximum brightness gave 32 lux at the eye. Read for 4 hours before bedtime, 5 evenings in a row, it suppressed 55% of evening melatonin, made it arrive more than 1 h 30 min later and lengthened the time to fall asleep by nearly 10 minutes, compared with a paper book.
4. Held close to the face at maximum brightness, a tablet gave about 70 lux at the eye and suppressed 19% of melatonin after 2 hours, in 12 people (Nagare, 2019): less than the curve says, since the curve was made with light from a whole room. Viewing time and how much of the field of view the screen takes up also matter.
5. Ordinary home lighting in the evening, about 140 lux, already suppressed children’s melatonin in Higuchi’s study (2014). In 116 young adults, room light under 200 lux made melatonin arrive later in 99% of them and shortened its duration by about 90 minutes (Gooley, 2011).
6. At 580 lux, melatonin was 88% suppressed in children about 9 years old, compared with 46% in adults: almost twice as much (Higuchi, 2014, in 5 children and 6 adults).

1. Norepinephrine arrives
   At night, the nerve ending releases norepinephrine onto the cell. It binds to the beta receptors on its surface, which raise a small messenger inside the cell, cAMP (cyclic AMP). As long as norepinephrine keeps arriving, cAMP stays high (Ganguly, 2001; Gastel, 1998).
2. A bodyguard: the 14-3-3 protein
   The handles let a pair of 14-3-3 proteins wrap around AANAT. Held this way, the enzyme grips serotonin better, and a second enzyme, ASMT, finishes the melatonin, which leaves the cell right away. 14-3-3 also hides the phosphates and protects AANAT from destruction (Ganguly, 2001; Klein, 2007).
3. Light cuts the signal
   A lamp comes on in the middle of the night. The eye alerts the clock, which puts the brake back on the nerve route (tab 1): norepinephrine stops arriving, and cAMP falls back in the cell (Gastel, 1998).
4. 14-3-3 lets go
   Without cAMP, nothing holds 14-3-3 in place anymore: it lets go of AANAT, and enzymes called phosphatases remove its phosphates. On its own, AANAT barely works. This detail was observed in animals, in the retina, which also makes melatonin (Pozdeyev, 2006; Ganguly, 2001).
5. The proteasome cuts it up
   AANAT on its own goes to the proteasome, a barrel inside the cell that cuts proteins into small pieces. In rats, AANAT activity drops by half in about 3 minutes after the lamp comes on, one of the fastest changes known for this type of enzyme. The gland stops producing, and the melatonin already in the blood drops by half in about 45 minutes (Klein, 1972; Gastel, 1998; Harpsøe, 2015).
6. The next evening, it all starts again
   There is no stock of AANAT. The next evening, norepinephrine comes back and the cell has to make new AANAT. In some species, the AANAT gene is also read much more at night; in all of them, it is mainly the protection against the proteasome that decides. The result is a switch that turns off in a few minutes (Ganguly, 2001; Klein, 2007).

1. It resets the clocks
   In the evening, the rise in melatonin tells the brain clock that night is starting. Taken as a pill, it shifts this clock: in the afternoon, it moves it earlier; just after waking, it moves it later (Burgess, 2010). In 6 out of 7 blind people, whose clock ran half an hour late each day for lack of light, 10 mg every evening brought it back to 24 hours (Sack, 2000). In 9 out of 10 trials, taken around bedtime on arrival, it reduced jet lag after 5 or more time zones (Herxheimer, 2002).
2. It helps the body cool down
   At night, it opens the small blood vessels of the hands and feet: heat escapes and the body’s core cools slightly, which goes along with falling asleep (Kräuchi, 1997). In young women, blocking nighttime melatonin with a drug reduced the day-night temperature difference by about 40%; giving it during the day lowered body temperature (Cagnacci, 1992). It prepares for sleep without forcing it: as a pill, it shortened the time to fall asleep by only 7 minutes on average (Ferracioli-Oda, 2013).
3. It measures how long nights are
   The longer the night, the longer melatonin lasts: its duration tells the season. In mammals that breed in a specific season, this signal passes through the hypothalamus and sets the reproductive hormones (Malpaux, 2001). In sheep and goats, a melatonin implant under the skin brings the breeding season forward (Chemineau, 1993). In humans, the signal is weak: in 55 healthy volunteers, it lasted as long in winter as in summer (9.0 and 8.9 hours); in 55 people with seasonal depression, longer in winter (9.0 versus 8.4 hours) (Wehr, 2001).
4. It tells the pancreas it’s night
   The pancreas cells that make insulin carry melatonin receptors. In 21 women, 5 mg of melatonin taken 15 minutes before a drink with 75 g of sugar made blood sugar rise higher, in the morning as in the evening; in the morning, this was mainly because less insulin came out (Rubio-Sastre, 2014). A common variant of the gene for its MT2 receptor is linked to type 2 diabetes (Lyssenko, 2009). Researchers still debate whether this is a useful brake or a harmful one: it may all depend on when high melatonin and a meal overlap (Garaulet, 2020).
5. Antioxidant, cancer: still debated
   It is often said that melatonin protects cells from oxidation. These effects have been seen mostly in the lab and in animals (Reiter, 2016). Based on calculations from animal studies, humans would need doses of around 100 mg a day, far more than the 2 to 10 mg used in trials, and large trials have yet to be done (Cardinali, 2024). Night shift work is classified as “probably carcinogenic” (IARC, 2019); it clearly suppresses melatonin, but its role in cancer has not been proven in humans.

Other texts from the animation

• Night mode: on a tablet at full brightness, 12% of melatonin suppressed after 2 hours instead of 19%, a gap too small to be sure of in 12 people (Nagare, 2019). So the curve does not move: brightness matters more than color.