Early morning wake-up, follow-up post with more info.

Serotonin, tryptophan? or a high glycemic index diet with too little omega 3 fatty acids? Or is the bedroom too hot? or too bright? Poor sleep can have many underlying factors.

There were questions about my last post, and the short answer is - I didn’t find references exactly supporting my title statement. Is early morning wake-up/insomnia due to “low serotonin”? Maybe not as much as serotonin and norepinephrine imbalance. St. John’s Wort modulates both and seems to consistently help insomnia sufferers, while 5-HTP, a serotonin precursor, does not consistently help insomnia sufferers. Serotonin is more involved in wakefulness and is present in higher quantities in the brain during wakefulness. Sleep and wakefulness are very complex and occur as an interplay between cortisol levels and other chemicals.

Coffee at night can/will keep people awake, for a while, but once too exhausted, it stops working as an alertness aid. Photo by freestocks on Unsplash

Caffeine is known as a stimulant to help keep us awake, but if the body is too sleep deprived, it stops working and sleep (and a car crash) are likely to follow an effort to keep going on caffeine alone. Better at that point, if going is a need, to take a break for a walk, and a protein snack. See this post for a list of tips about drowsy driving, transcendingsquare.com. My archives here do have the post but with zero photographs. Here is the follow up post with a DIY project to convert your hatchback back seat into a sleep platform, (transcendingsquare.com).

Tyrosine is an amino acid with stimulating properties which may be why a protein snack can help promote wakefulness when feeling too tired to continue (taking a nap is a better idea though).

“Tyrosine is a nonessential amino acid whose metabolite is norepinephrine (NE) which is a neurotransmitter. NE is released at its lowest levels during sleep and rises during wakefulness. The level of NE dramatically increases during situations of stress or danger, which is called the fight-or-flight response. NE is long known for its role in maintaining general arousal [69] which has also been confirmed using mouse models.” (Zhao, et al., 2020)

~~ My main post on Sleep and Health ~~

Sleep and health

In that post, I have a reference to a Symptoms of Serotonin Deficiency list as a reference for ‘waking up at 4 am’. Changes in sleep is listed as a potential symptom.

“If reawakening in the middle of the night is consistently happening around 4:00 am then low serotonin levels may be a problem. (University Health News) Taking the precursor to serotonin, 5HTP or the herbal St John's Wort, may help provide your body with serotonin.”

What I learned yesterday, (post), digging a little deeper into serotonin and sleep, is that it is an interplay between a few neurotransmitters, so just trying to increase serotonin alone probably doesn’t work, which explains why 5-HTP doesn’t have as positive feedback on insomnia.net as St. John’s Wort did. (That site was simple, patient oriented - these things seem to help for this short-text reason. Or this other thing (5-HTP) has variable results for consumers.)

Chronically low serotonin is likely a causal problem of poor sleep though, in which case take the niacin or 5-HTP early in the day, because it is during wakefulness that we need larger amounts of serotonin. Taking my niacin in the evening can keep me awake much longer into the night than desired.

“4.1. Tryptophan

Tryptophan is the substrate for serotonin which has been intensively studied on its role on sleep for many decades [20]. Although the role of serotonin on sleep has been under debate, there is a general agreement that serotonin is a major sleep mediator which first increases wakefulness but then increases NREM sleep [20]. Considering the role of serotonin, it has been indicated that supplementation of tryptophan (1 g or more) produces an increase in subjective sleepiness and a decreased time to sleep especially in subjects with mild insomnia [62]. A random double-blind experiment on healthy adults suggested that tryptophan consistently reduced sleep latency which is associated with blood levels [63]. Recently, a Japanese study of younger aged population concluded that tryptophan ingested during breakfast is required for children to keep a morning-type diurnal rhythm and maintain high quality sleep [64]; however, this study did not involve supplementation of tryptophan, instead they calculated the tryptophan-index based on food they consume.” (Zhao, et al., 2020)

Low omega 3 fatty acids may be a negative for a good night’s sleep. A diet high in simple carbohydrates, with an overall high glycemic index (diabetes promoting), has been linked to insomnia, while a higher fiber diet with non-juice fruit servings was associated with less insomnia. (Zhao, et al., 2020)

“However, other studies, including a recently published by Gangwisch et al., suggested that high glycemic index and glycemic load diets is a risk factor for insomnia [28]. This prospective study of a much larger population of postmenopausal women population demonstrated that high-GI diet was associated with increased insomnia incidence over 3 years, and higher intakes of dietary added sugars, starch, and nonwhole/refined grains each were associated with higher incidence of insomnia. Moreover, they found higher fiber content in food as well as nonjuice fruit were associated with a lower prevalence and incidence of insomnia. This conclusion is consistent with a previous study that high intake of confectionary is related with poor sleep quality among middle-aged female Japanese workers [29]. Supporting this concept, a study on short-term consumption of a very low-carbohydrate (VLC) diet over 48 h comparing to a control mixed diet on sleep indices suggested promotes SWS (deep sleep stage) and reduces the percentage of REM sleep (“dreaming” sleep) [30].” (Zhao, et al., 2020)

Looking at why a high glycemic index diet causes insomnia led to suggesting that it is due to inflammatory effects, rather than it having something to do with tryptophan or serotonin balance. Eating rich foods late at night is harder on the liver and digestive system - work has to be done on digesting rather than on clean up, and use of nutrients for repair and growth. (Zhao, et al., 2020)

“Instead, they proposed that hyperglycemia induced after high-GI diet and resulting compensatory hyperinsulinemia could induce the release of autonomic counterregulatory hormones including adrenaline, cortisol, glucagon, and growth hormone which contributed to insomnia [28, 34]. Moreover, high-GI diets have also been shown to stimulate inflammatory immune responses [35] and lead to alternations in intestinal microbiome which may also profoundly affect sleep quality [15].” (Zhao, et al., 2020)

Low vitamin D levels are also associated with insomnia, and overall inflammation may be causal for that effect. Taking vitamin D supplements may help sleep, but daytime sunshine would help more though, by helping us create vitamin D and by promoting good circadian cycle function. Lower vitamin C intake (of dietary sources like citrus fruits & vegetables) was associated with shorter sleep and was also shown with differences in blood plasma levels of vitamin C. Studies on B6, B12, or a B complex have been inconclusive regarding sleep and the B12 and B complex may even have caused negative results. (Zhao, et al., 2020) That makes me wonder if cyanocobalamin and folic acid are causal of increased inflammation . . . and negative sleep results.

Personally, I really do need high dose B6 in order to dream at all. Not dreaming is a side effect of pyroluria and chronically low B6. When following my supplement plan, I take a vit. B6 in the morning along with other Bs, and another at night by itself. Sticking with that consistently helps me to dream sometimes but I still don’t dream much.

GABA does help sleep. (Zhao, et al., 2020)

“There are many studies showing the sleep-promoting effect of GABA, for example, Byun et al. reported a study of 40 patients with insomnia receiving 4 weeks of GABA (300 mg/day) have decreased sleep latency and increased sleep efficacy [66]. The mechanisms of sleep induction by GABA through their receptors have been reviewed [67]. GABA receptor agonists have also been used to induce sleeping [68].” (Zhao, et al., 2020)

Keep it cool at night for best sleep

Our body and brain temperature drops down as we get ready to sleep, so if it is too hot, or the body isn’t able to regulate temperature well, then insomnia may result. A cool compress on the forehead can help the brain with cooling down.

“**The tip about keeping gel packs in the freezer for use as a cold compress for the forehead that I mentioned for insomnia in a previous post (about the glymphatic system within the brain and its potential role in prevention of Alzheimer's disease), is something that I have found helpful in the past for migraines. I tried it recently for insomnia after learning in the course about sleep and neurobiology that a “biothermal device” had been found helpful in sleep lab studies for patients with insomnia. (Sleep, Neurobiology, Medicine and Society, coursera.org)”

My main post on Sleep and Health has the link to a great neurobiology course about sleep on the MOOC site Coursera. Do the not required, Honors (hard), sections for greater understanding of the complexity of sleep regulation. It is enrolling now for a July start-up session. I highly recommend this course (can be free or a small fee to get a certificate of proof of completion) (Coursera).

I did spend a lot of time on the Honors sections, and took notes and studied, in part because I had signed up for an even more difficult Neurobiology MOOC (maybe this one, Duke U. also enrolling now). I took the sleep neurobiology course and two other general Neurobiology MOOCs and then retried the hard one and managed to pass it - using 3 by 5 cards and other study skills. Most MOOCs have easier quizzes than are given in a real college course, but the Duke University course, had the really hard college level tests - which is you want for a neuroscientist. Giving out A’s easily, for topics that aren’t easy, is unfair to future employers or consumers.

St. John’s Wort can cause sun sensitivity - a hive-like skin reaction after not much time in the sun. *Flush niacin seems to cause a similar effect if taken prior to sitting outside in summer sunshine.

An additional caution about yesterday’s post - St. John’s Wort can cause photosensitivity - maybe more easily getting a sunburn or hive like reaction after spending time in the sun. This Quora response suggested taking SSRI’s instead of St. John’s Wort, but SSRIs have a lot of side effect risks too (depletion of nutrients can occur leading to mitochondrial dysfunction).

More information about ‘photosensitivity’ versus ‘phototoxicity’ is available in this review article. (Di Bartolomeo, et al., 2022) I did have sun sensitivity for a while and I just wore long sleeves and avoided the sun. Maybe it was the St. John’s Wort. I haven’t been using that herb currently - salicylate excess led to my cutting out lots of incidentals in an attempt to get my health stable again.

Disclaimer: This information is provided for educational purposes within the guidelines of fair use. While I am a Registered Dietitian this information is not intended to provide individual health guidance. Please see a health professional for individual health care purposes.

Reference List

(Di Bartolomeo, et al., 2022) Di Bartolomeo L, Irrera N, Campo GM, Borgia F, Motolese A, Vaccaro F, Squadrito F, Altavilla D, Condorelli AG, Motolese A, Vaccaro M. Drug-Induced Photosensitivity: Clinical Types of Phototoxicity and Photoallergy and Pathogenetic Mechanisms. Front Allergy. 2022 Jun 20;3:876695. doi: 10.3389/falgy.2022.876695. PMID: 36238932; PMCID: PMC9552952. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9552952/

(Zhao, et al., 2020) Zhao M, Tuo H, Wang S, Zhao L. The Effects of Dietary Nutrition on Sleep and Sleep Disorders. Mediators Inflamm. 2020 Jun 25;2020:3142874. doi: 10.1155/2020/3142874. PMID: 32684833; PMCID: PMC7334763. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7334763/