Having Trouble Sleeping? Vitamin B12 May Help

Vitamin B12 deficiency is common in the US, affecting up to 15% of the general population, and up to 30% of older adults. Low B12 status results in several neurological changes including numbness in the hands and feet, difficulty maintaining balance, depression, confusion, dementia, poor memory, and poor sleep.
National Institutes of Health: Vitamin B12

I’ve been researching the link between vitamin B12 and sleep. There does seem to be an effect. Here are some things I learned:

  • Vitamin B12 aids sleep by causing both an increase in production of melatonin and an earlier release of melatonin. Melatonin is a hormone that, among many functions, regulates sleep timing. B12 acts directly on the pineal gland, an endocrine gland that synthesizes melatonin.
  • All of the studies I looked at used the form of vitamin B12 called methylcobalamin, either injected or given orally.
  • Methylcobalamin seems to work better as a sleep aid when it is used in conjunction with light therapy – exposure to bright/blue light for several hours upon awakening, and reduction of bright/blue light several hours before bedtime.
  • Methylcobalamin is especially helpful for people who have difficulty falling asleep [delayed sleep phase syndrome (DSPS)], and difficulty waking in the morning or feeling refreshed upon waking.
  • The effect of administered methylcobalamin is dose-dependent. If you take too little, or it doesn’t get absorbed (and there are lots! of barriers to B12 absorption), it won’t help.
  • The production of melatonin follows the serotonin pathway:
    tryptophan (an essential amino acid) –> 5-hydroxy-tryptophan (5-HTP) –> serotonin –> melatonin. Interestingly, B12 is known to improve mood too, via serotonin?

I found this great round-up of methylcobalamin studies by Dr. Sarma (http://www.drsarma.in/files/medicine/Other%20topics/). What he says about B12 and sleep pretty much mirrors what I discovered:

Those who can’t get to sleep at night may need vitamin B12. Studies show that B12 causes an earlier release of melatonin at night which resets the sleep-wake cycle. (Melatonin has been called “the sleep hormone” because of its effects on sleep). B12 acts directly on the pineal gland to provoke a faster release of melatonin. At the tail end, B12 causes melatonin to drop off faster. B12 helps you get to sleep earlier, and may help you wake up earlier if you leave a curtain open to the morning sun. B12 sensitizes you to morning light, which helps you wake up. Very serious sleep-wake disorders have been successfully treated with vitamin B12 in the methylcobalamin form, although it may not work for everyone. Unfortunately, the vitamin doesn’t help people who want to cut down on their sleep time altogether.

B12 has many benefits, including the reduction of homocysteine, restoration of normal sleep patterns, and mood effects. B12 deficiency is a fairly common deficiency in elderly people who frequently have disrupted digestion. It can cause symptoms that look exactly like Alzheimer’s disease, and it’s crucial for the retention of folate in cells.

It has been documented that the level of B12 decreases every year with age.

According to the recent data, 2,000 micrograms/day of oral B12 cures the symptoms of B12 deficiency. … The dose of oral B12 supplements for sleep disorders is 3000 mcg a day. … In published studies, it took four weeks for the sleep effect – so be patient.

The rest of this post is a collection of studies I found on vitamin B12 and sleep. I’m using this post as a repository, so I’ll probably be updating it over time.

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This was an interesting study. It found that B12, in combination with 3 hours of bright light in the morning (7:00 to 10:00), improved sleep in people whose problem was delayed sleep at night. It reset the sleep phase causing people to fall asleep earlier and wake up earlier and more refreshed:
Vitamin B12 enhances the phase-response of circadian melatonin rhythm to a single bright light exposure in humans, Neuroscience Letters, 1996

Eight young males were subjected to a single blind cross-over test to see the effects of vitamin B12 (methylcobalamin; VB12) on the phase-response of the circadian melatonin rhythm to a single bright light exposure. VB12 (0.5 mg/day) or vehicle was injected intravenously at 1230 h for 11 days, which was followed by oral administration (2 mg x 3/day) for 7 days. A serial blood sampling was performed under dim light condition (less than 200 lx) and plasma melatonin rhythm was determined before and after a single bright light exposure (2500 lx for 3 h) at 0700 h. The melatonin rhythm before the light exposure showed a smaller amplitude in the VB12 trial than in the placebo. The light exposure phase-advanced the melatonin rhythm significantly in the VB12 trail, but not in the placebo. These findings indicate that VB12 enhances the light-induced phase-shift in the human circadian rhythm.

In this next study, “28% of patients were effectively treated with either vitamin B12 alone or in combination with bright light
A multicenter study of sleep-wake rhythm disorders: therapeutic effects of vitamin B12, bright light therapy, chronotherapy and hypnotics, Psychiatry and Clinical Neurosciences, 1996

One hundred and six subjects with primary sleep-wake rhythm disorders [13 non-24 hour sleep-wake syndrome (non-24), 76 delayed sleep phase syndrome (DSPS), 11 irregular sleep-wake pattern (irregular) and six long sleepers] were treated with vitamin B12, bright light, chronotherapy and/or hypnotics. These therapies caused moderate or remarkable improvement in 32% of the non-24, 42% of DSPS, 45% of irregular and 67% of long sleepers. A lack of adequate sleep, unpleasant feelings at waking and daytime drowsiness were also improved in DSPS.

This was an open label study of 20 teenagers. Methylcobalamin seems to aid sleep when it is combined with bright light in the morning:
Circadian rhythm sleep disorders in adolescents: clinical trials of combined treatments based on chronobiology, Psychiatry and Clinical Neurosciences, 1998

Delayed sleep phase syndrome (DSPS) and non-24-h sleep-wake rhythm are circadian rhythm sleep disorders that are common in adolescents. Most patients have difficulty adjusting to school life, poor class attendance or refuse to go to school. Since a treatment has not been established, the present paper is presented to propose a strategy for treating circadian rhythm sleep disorders in adolescents, based on our clinical studies. Twenty subjects (12 males and eight females, mean age 16.2+/-1.7 years) participated in the study. The onset of sleep disorder occurred between the ages of 11 and 17. The most common factors affecting the onset of disorders were changes in social environment. The subjects kept a sleep-log for the periods before and during treatments. The treatments were based on chronobiology: resetting the daily life schedule, chronotherapy, regulation of the lighting environment, methylcobalamin, and/or melatonin. Bright light exposure was successful in 10 patients, of whom four were treated with methylcobalamin. Melatonin treatment was successful in two patients (one with and one without chronotherapy). Thirteen of the 20 patients were successfully, treated with therapies based on chronobiology. After consideration of these results, a step-by-step procedure of combined treatments for the circadian rhythm sleep disorders is proposed.

In this study, 1 mg of methylcobalamin given 3 times/day after meals (that’s the best time to take it because you release intrinsic factor (IF) from parietal cells lining the stomach when you eat, and IF aids absorption) for 4 weeks didn’t show effect compared to placebo, but that suggests, as in other studies, its benefit may be dependent on its interaction with light:
Vitamin B12 treatment for delayed sleep phase syndrome: a multi-center double-blind study, Psychiatry and Clinical Neurosciences, 1997

The active form of vitamin B12 (methylcobalamin) has been reported to be effective on sleep-wake rhythm disorders. Previous studies, however, were performed under open trial, and the effect of vitamin B12 has not been properly evaluated. The aim of this double-blind study was to investigate the efficacy of methylcobalamin on delayed sleep phase syndrome (DSPS). Methylcobalamin (3 mg/day) or placebo was administered for 4 weeks. The subjects were 50 patients with DSPS aged 13-55 years (26.8 +/- 1.3), 27 of whom received the active drug while 23 received the placebo. No significant differences were observed between the 2 groups in subjective evaluations of mood or drowsiness during the daytime or in night sleep by sleep-log evaluation. These results indicate that 3 mg methylcobalamin administered over 4 weeks is not an effective treatment for DSPS.

This study was similar to the one above. B12 showed a non-significant tendency to improved sleep. Its benefit may be dependent upon its interaction with bright morning light:
Double-blind test on the efficacy of methylcobalamin on sleep-wake rhythm disorders, Psychiatry and Clinical Neurosciences, 1999

The therapeutic effect of methylcobalamin (Met-12) on sleep-wake rhythm disorders was examined in a double-blind test. In the test group which was given a large dosage, a higher percentage of improvement was found compared to the control group with a small dosage, although the difference was not significant. The test group inconsistently showed significant improvement in both the sleep-wake cycle parameters and in clinical symptoms. The tendency was for the results to show a beneficial effect of Met-12 on rhythm disorders. However, because the percentage of improvement was low and significant improvement was inconsistent, Met-12 might be considered to have a low therapeutic potency and possible use as a booster for other treatment methods of the disorders.

Case study:
Successful treatment of human non-24-hour sleep-wake syndrome, Sleep, 1983

The authors report a case in which a non-24-h (hypernychthemeral) sleep-wake cycle appeared as a late complication of a more fundamental disturbance in the quality of sleep (difficulty falling asleep, frequent awakenings, nonrefreshing sleep). The sleep disturbance began abruptly after a series of stressful events. The patient reported that he extended his hours of bedrest in the morning in order to increase his total sleep time and feel mor rested, and that he gradually extended his hours of activity in the late evening in order to increase his drowsiness and ability to fall asleep. At first this behavior, which was a deliberate attempt to compensate for inefficient nighttime sleep, led to a delayed sleep period, as also occurs in the delayed sleep phase syndrome. After several years in which sleep efficiency progressively deteriorated, this behavior led to a non-24-h free-running sleep-wake cycle. After the patient was treated with thyroxine for borderline hypothyroidism, and then flurazepam and finally vitamin B12, his sleep disturbance progressively improved and his sleep-wake cycle shortened. After B12 treatment he was able to advance the timing of ;his sleep period for the first time in nearly 10 years and to follow a normal 24-h sleep-wake regimen.

Case study:
Vitamin B12 treatment for sleep-wake rhythm disorders, Sleep, 1990

Vitamin B12 (VB12) was administered to two patients suffering for many years from different sleep-wake rhythm disorders. One patient was a 15-year-old blind girl suffering from a free-running sleep-wake rhythm (hypernychthemeral syndrome) with a period of about 25 h. In spite of repeated trials to entrain her sleep-wake cycle to the environmental 24-h rhythm, her free-running rhythm persisted for about 13 years. When she was 14 years old, administration of VB12 per os was started at the daily dose of 1.5 mg t.i.d. Shortly thereafter, her sleep-wake rhythm was entrained to the environmental 24-h rhythm, and her 24-h sleep-wake rhythm was maintained while she was on the medication. Within 2 months of the withholding of VB12, her free-running sleep-wake rhythm reappeared. The VB12 level in the serum was within the normal range both before and after treatment. The other patient was a 55-year-old man suffering from delayed sleep phase syndrome since 18 years of age. After administration of VB12 at the daily doses of 1.5 mg, his sleep-wake rhythm disorder was improved. The good therapeutic effect lasted for more than 6 months while he was on the medication.

Study on rats showing B12 acts on pineal gland causing increase in production of melatonin in early evening:
Methylcobalamin amplifies melatonin-induced circadian phase shifts by facilitation of melatonin synthesis in the rat pineal gland, Brain Research, 1998

Effects of methylcobalamin (methyl-B12), a putative drug for treating human circadian rhythm disorders, on the melatonin-induced circadian phase shifts were examined in the rat. An intraperitoneal injection of 1-100 microg/kg melatonin 2-h before the activity onset time (CT 10) induced phase advances of free-running activity rhythms in a dose-dependent manner (ED50=1.3 microg/kg). Injection of methyl-B12 (500 microg/kg) prior to melatonin (1 microg/kg) injection induced larger phase advances than saline preinjected controls, while the injection of methyl-B12 in combination with saline did not induce a phase advance. These results indicate amplification of melatonin-induced phase advances by methyl-B12. Pinealectomy abolished the phase alternating effect of methyl-B12, suggesting a site of action within the pineal gland. In fact, methyl-B12 significantly increased the content of melatonin in the pineal collected 2-h after activity onset (CT 14). In contrast, no difference in melatonin content was found at CT 10, indicating that the effect of methyl-B12 may be gated after the activity onset time when endogenous melatonin synthesis is known to increase. These results suggest that methyl-B12 amplifies melatonin-induced phase advances via an increase in melatonin synthesis during the early subjective night at a point downstream from the clock regulation.

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So, B12 doesn’t by itself aid sleep, it’s B12’s effect on melatonin that aids sleep. And melatonin, in turn, is affected by light and dark. The two together (B12 plus light early/dark late) have a profound effect on sleep.

4 thoughts on “Having Trouble Sleeping? Vitamin B12 May Help

  1. Melinda

    This is really interesting. I bought some NOW-brand, 1000 mcg, methylcobalamine tabs that you can chew or let dissolve in your mouth. The bottle doesn’t say, however, whether it should be taken with or without food, or what time(s) of day one should take it. If it’s going to affect melatonin, it seems like maybe timing would be important, but I don’t know. On the bottle it says that it could/should be taken with a B-complex pill, but again, I don’t know if that’s good advice or not. Any ideas? I’m glad you’re writing about it.

    Reply
  2. Bix Post author

    We absorb only a few micrograms, that’s micrograms, not milligrams, every 4 hours or so. If you want to maximize absorption, take a small amount every 4 hours with food (in the middle of or right after but not before food). B12 is best absorbed with intrinsic factor which is secreted from the parietal cells of the stomach when we eat.

    B12 attached to protein in food, like meat, has to be separated from that protein in the stomach – which requires stomach acid – which is something older people have less of (you also have less of it if you take an antacid). B12 in supplements does not need to be separated from protein and is more efficiently absorbed.

    I’m not sure why so many studies use such high oral dosages … 1000 micrograms and up. I can only assume there is a good amount of passive absorption in the presence of a high dose.

    From what I read, even though it’s counterintuitive to me … B12 taken in the morning enhances alertness during the day and B12 taken in late afternoon enhances sleepiness at bedtime. It’s because it works, not by itself, but with melatonin (and probably other hormones) and light. It helps to get rid of melatonin during the day (thus, the feeling of “energy”) and brings melatonin on at night (thus, the feeling of lethargy).

    I have read that vitamin B6 works with B12 somehow. But it wasn’t my focus so I don’t know much. B6, though, is quite easy to get lots of non-animal foods … peppers, cabbage, spinach, etc. And there are not so many obstacles to absorption as there are with B12 so I don’t see the need to supplement B6.

    I do wonder why the body has so many unique and hard-to-overcome mechanisms to keep us from absorbing B12. It’s as if a little is a good thing but a lot could cause harm.

    Reply
  3. Bix Post author

    I have methylcobalamin liquid drops. One drop has about 40 micrograms. I squirt a drop or two right into my mouth after a meal. I think that more closely approximates how we would get it naturally, in a meal.

    Reply

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