I am not quite sure when Insomnia became an issue for me. I was born in 1960 and it may have been in the early 2000s (20 years ago at the time of writing), but I know it was an issue for a long time. I had tended to get into the habit of normally going to sleep drunk, waking up in the middle of the night and then hoping to get some reasonable sleep between perhaps 6am and 7am so that I was functional for the next day.
In 2016, however, I started to keep some records as to particularly what I was drinking, but also my blood pressure and heart rate on waking and going to sleep. I then decided to put some serious effort into improving my sleep patterns. I am pleased to say that I have made good progress with improving sleep and getting rid of insomnia. I have decided to write this blog post. In part to enable me to structure the medical research that I have collated and in part because I have found that people are unsurprisingly often quite interested in my experience in this area. Hence I will write this partially from the point of view of suggestions as to things to do which can improve sleep and health more generally.
What I intend to do is to update this particular post. I am not medically qualified and all I am writing about are my own experiences and a collation of information I have found on the internet. Hence I am not giving medical advice. Different people are different. I am quite big being 6 foot 2 and weighing between 21 stone (130kg) and a target of 14-16 stone (98-101 kg). I am currently 105kg, but my weight is reducing. (as a result of eating less intentionally). If people take dietary supplements it will vary which ones help people and people will suit different quantities. For example Vitamin D is fat soluble and if you are obese - as I was until recently - you need to take more to have the same effect.
Hence I would suggest that you read this and use it as a basis of suggestions for research rather than a recipe for improving health and getting rid of or reducing insomnia. Talking to your medical practitioner about the suggestions before taking anything is worth considering once you have done your own research.
Two youtube videos
Insomnia harms health
There are many ways in which insomina harms health. Hence if you reduce insomnia you are likely to have other health improvements. My own blood pressure and resting heart rates have come down. Some of this is as a result of losing weight, but the effect of reducing insomnia also helps. The body uses sleep to repair itself hence if people are not sleeping well that process does not work properly. I will focus in this post on reducing insomnia, but that is also about improving health.
Many people are used to a situation where they are really tired in the afternoon and often need a nap. My experience is that I have been able to improve my sleep patterns such that I can go through the day being effective and sleep only at night.
CBT should always be tried
CBT is Cognitive Behaviour Therapy. That is really a fancy title for improving what you do. Part of this is also known as Sleep Hygiene. People who are reading things on the internet are likely to have seen these sort of things listed elsewhere. However, here is a list.
Warning: Vitamin D
Some people have a genetic mutation which means they do not handle Vitamin D well. If you think you may fall into this category get it checked. Here is a media story about Baby deaths mystery from 1930s solved by researchers finding 'abnormal' gene shape link to vitamin D side-effects
Make sure you have enough Vitamin D
People are I think becoming more aware of the importance of Vitamin D. From a sleep point of view, however, you need to be careful not to take Vitamin D too late in the day. Vitamin D goes through an interesting metabolic cycle where it first gets converted (Vitamin D Metabolism, Mechanism of Action, and Clinical Applications) to 25OHD (Calcifediol) in the liver and then the kidneys convert it to 1,25-dihydroxyvitamin D (1,25(OH)2D - Calcitriol) which is a hormone and has the main effects. There are many reports that if you take it in the afternoon or evening then it holds back sleep. Similarly if you are using a 311nm Ultra Violet light or even the Sun to generate your vitamin D then it is best not to do this in the evening before going to sleep. The Sun is quite helpful in this in that the Sun has been well trained not to shine brightly just before you should be sleeping. However, I would not suggest switching on a UV light in the evening. I have not found a paper which studies this formally, but I have seen lots of papers talking about this.
Vitamin D does a lot of other things. You do need to be careful not to take too much vitamin D. (Vitamin D Toxicity–A Clinical Perspective) However, the example of someone who got too much calcium in their blood from about 10,000 iu a day was from someone who was also sunbathing. In the winter when there is not enough UVB around (particularly in England) people do need Vitamin D. The NHS in England recommends 400iu, in Germany they recommend 800iu. I personally was taking 3000iu a day which I originally wrote this, but remember different people will need different amounts. I later moved to 1000iu a day because I lost about 15 more kg plus possibly 1000-2000 IU in 25OHD. Vitamin D is fat soluble so if you take it in oil then perhaps you get about 30% more than taking the same quantity of Vitamin D in tablet form.
What I find if I have too much vitamin D (and that is not hypervitaminosis D,but just too much on the day or late in the day) is that I have problems with sleep maintenance at about 2am. I find that if I take a relatively heavy dose say 24,000 iu (iu being the measurement that allows comparison of different types of vitamin) then it can cause sleep maintenance problems for a couple of days. My guess is that this is because it takes a bit of time to process it into 250HD, but that's just a guess. However, if I have enough vitamin D and don't take it for a day things work OK until the vitamin D levels go down.
The metabolism of Vitamin D is really quite complex and cannot be treated as having a half life particularly as it converts into different things. However, it will hang around for a while so if you end up taking too much it won't go away by just stopping. If you really have overdone it and have hypercalcaemia (too much calcium) you may need some medical treatment.
Some reading: LARGE, SINGLE-DOSE, ORAL VITAMIN D SUPPLEMENTATION IN ADULT POPULATIONS: A SYSTEMATIC REVIEW of 30 papers looking at a really large dose Safety of 50,000-100,000 Units of Vitamin D3/Week in Vitamin D-Deficient, Hypercholesterolemic Patients with Reversible Statin Intolerance The authorities tend to recommend a maximum of 4,000 IU per day. I have noticed issues with sleeping at 6,000iu per day and I think that is a metabolic issue and not something that would lead to hypervitaminosis, but I am not a medic. What I think is happening is that there is a high level of unprocessed Vitamin D floating around in the blood. I have seen a paper that indicates that this can cause problems. Until the Liver has switched it to 25OHD it can be a bit of a nuisance. It is going to take some time for the liver to process it.
Hence with Vitamin D. Remember to look at taking it in the morning. That also means not using a UV light at night. If you are sunbathing in the summer you won't need as much of a supplement (or any) compared to the winter.
This is a particularly interesting paper Evaluation of vitamin D3 intakes up to 15,000 international units/day and serum 25-hydroxyvitamin D concentrations up to 300 nmol/L on calcium metabolism in a community setting which looks at higher doses of D3. It concludes "Serum 25(OH)D concentrations up to 300 nmol/L were found to be safe." It seems that the body safely stores Vitamin D in 25OHD form (which is logical if it comes in mainly during the summer). However, my own experimentation concludes that there is a limit on the rate at which D3 is converted to 25OHD (which is obviously going to be the case) which would argue for a daily supplementation rather than weekly.
This article medcape Says 25OHD has a half life of 15 days and the hormone has 15 hours. Alternatively this article Vitamin D has longer than expected half-life: Tests may not show true 'plateau' says it is two months. I think actually both are wrong. The conversion to the hormone in the kidneys is controlled by feedback systems. Hence it would not so much have a half life like a radioactive nucleus, but intead a consumption rate primarily perhaps also linked to a half life, but dominated by a consumption rate. One would assume that the consumption rate would vary. Hence if people get a really high 25OHD it will take quite a while to get rid of it (hence the argument not to overdose on D3).
There can be a recommendation that if taking Vitamin D supplements it is best not to also take calcium supplements but to get additional calcium via the diet if needs be. Mobilising vitamin D from adipose tissue: The potential impact of exercise is an interesting article that also looks at the storage of D3 in fat tissue particularly for fat people. It makes the point that potentially many years of the RDI can be stored and potentially it can be recovered by exercise. People can overdose on vitamin D if they have kidney problems which restrict conversion of 25OHD to the hormone or on 10,000 iu a day in other circumstances. A key point about Vitamin D is to tell any medical professionals if you are taking it so they can take that into account for a diagnosis if there are any issues to look at.
Further on the metabolites
It is, of course, possible to take 25OHD directly or the hormone itself. I would discourage people from taking the hormone itself as the body manages carefully the level of hormone that is available. However, there are potentially advantages in taking 25OHD. This study looks at the options: Cholecalciferol or Calcifediol
Quoting: "Indeed, when using dosages ≤ 25 μg/day, serum 25OHD increased by 1.5 ± 0.9 nmol/l for each 1 μg cholecalciferol, whereas this was 4.8 ± 1.2 nmol/l for oral calcifediol." So let us say from this given 1 μg of D3 is 40iu, 1 μg of Calcifediol is about 120iu. Otherwise I have used figures of 200iu for 1 μg of Calcifediol. (One nmol/L = 0.4 ng/mL) Alternatively to take serum 250HU up by 10 nmol/l. Normal range for serum level is quoted as various figures, but between 30 and 60 ng/m is one.
Hence using these figures (and remembering different people will respond differently) to move serum level by 10ng/ml requires a movement of 25nmol/l, which would require 17μg of d3 or 5.20 μg of Calcifediol ie about 600-700iu.
A systematic review and meta-analysis of the response of serum 25-hydroxyvitamin D concentration to vitamin D supplementation from RCTs from around the globe It gives a sort of answer. Perhaps stating take a bit more than the calculation above. Similarly with this Vitamin D Metabolism and Guidelines for Vitamin D Supplementation (2020 - Review) From the review:"Studies have shown that dosing with vitamin D3 required in the order of 150–180 d to reach something approaching a steady state. During the study period, concentrations of 25(OH)D increased with a slope (change/dose) of 0.70 nmol/L (0.28 ng/mL) for each 40 IU (1 μg) of vitamin D3 input, in subjects with mean baseline 25(OH)D value of 70.3 nmol/L (28.1 ng/mL).48 In an earlier study by the same authors, the change in 25(OH)D over the study period was 1.23 nmol/L (0.49 ng/mL) for each 100 IU (2.5 μg) of vitamin D3 input. In a summary of 13 studies carried out during the period 1977–1996, the increase in 25(OH)D varied from 1.47–8.75 nmol/L (0.59–3.5 ng/mL) per 100 IU (2.5 μg) of oral vitamin D intake.38 In subjects with an average 25(OH)D concentration of 47 nmol/L (18.8 ng/mL), treatment with vitamin D at concentrations of 1000 IU/d (25 μg/d) or 4000 IU/d (100 μg/d) increased serum 25(OH)D over 3 m to 69 nmol/L (27.6 ng/mL) and 96 nmol/L (38.4 ng/mL) respectively.49 In a review of 49 studies, authors conclude that the ‘rule of thumb’ is 5.0 nmol/L (2 ng/mL) increase of 25(OH)D for each 100 IU/d (2.5 μg/d) of ingested vitamin D.50 In a review of 76 trials published from 1984 to 2011 the average increase was 1.95 nmol/L (0.78 ng/mL) per 40 IU (1 μg) of vitamin D3 supplement per day.51 A summary suggests that trials that used similar doses could obtain changes in 25(OH)D that can vary 3–4-fold. A mean slope of 0.66 nmol/L per 40 IU/d (0.26 ng/mL per μg/d) was reported by Aloia et al.41 The individual slopes ranged from 0.15–1.49 nmol/L (0.06–0.60 ng/mL), virtually a 10-fold increase. Investigators either report the same slope for different dosage concentrations48 or a variable response dependent on the IU of vitamin D intake.41 " From this to get an additional 10ng/ml would require 1429, 889, 678-131 iu. I think part of the difficulty here relates to deficiency vs sufficiency vs plenty and part the difference between individuals.
There are three commercial versions of 25OHD that can be obtained I think they are all on prescription. These are Hidroferol, Dedrogyl and Rayaldee. Rayaldee has delayed release and is really quite expensive. I have no further knowledge of Hidroferol, but Dedrogyl seems to be worth a look. The advantage of taking 25OHD directly is that you don't end up with an excess of D3 which in my experience is not a nice thing as it can cause sleep problems. Roche produce Rocaltrol which appears to be available in the UK, but seems to be a really low dose (ie 0.25mcg or 0.5mcg a 10th or 20th of the single drop of 5mcg Dedrogyl).
This paper looks at whether taking a large amount of 25OHD can be counter productive in getting rid of vitamin D (inter alia) However, this compared single delayed release to bolus rather than daily. In a sense this fits with the idea that the serum level would go right up and upregulate (switch on) the CYP24A1 gene which generates an enzyme that switches 25OHD to 24,25(OH)₂D.
This paper looks at high levels of 25OHD and some being catabolised into 24,25(OH)₂D. The interesting question is whether that then has physiological functions or whether it just gets excreted having been metabolised a bit more. This comes into the debate as to whether there are three levels of vitamin d: Deficient, sufficient and plenty. In Plenty mode it gets used up doing other things (possibly via 24,25(OH)₂D), but if it pops back into sufficient then the essential functions are maintained. The hormone dihydroxyvitamin D (1,25(OH)₂D aka calcitriol) tends to be kept at pretty constant levels given enough 25OHD.
This means there is some uncertainty about how to take 25OHD to increase serum levels. Taking delayed release is one option. Another option is to take it a few times a day. Probably taking a big wodge at one time will cause some 25OHD to be converted to 24,25(OH)₂D. That may be a good thing and it may be a bad thing or it may be just futile. Linus Pauling Institute on Vitamin D
Some people say to take K2 M7 with Vitamin D3 Coffee man on D3 Looking at these articles it clearly helps to take some form of Vitamin K with Vitamin D, but that is a complex issue about which I have written a Separate page
Look at anthocyanins (not as bad as it sounds)
Anthocynanins are a type of chemical that can be used to make plants have a particular range of colour. I have found that Pomegranate juice, Blackberries and Black Turtle Beans (which can be found in Marks and Spencer 3 bean salad) all help with sleep. There is also research that recommends Tart Cherry juice. The common feature of these is that they all have anthocyanins in them. I have not as yet, however, found any research that substantiates this beyond my own experimentation.
There are various studies into heating anthocyanins Thermal and pH degradation kinetics of anthocyanins in natural food colorant prepared from black rice bran Effects of Cooking Methods on Anthocyanins and Total Phenolics in Purple‐Fleshed Sweet Potato In essence, however, cooking anthocyanins runs the risk of degrading them to not be effective. Hence best to eat the blackberries without cooking them first.
Consider melatonin
Melatonin is a really interesting hormone. In a sense Melatonin is the hormone of the night and Vitamin D is the hormone of the day. Melatonin does a lot of things. However, a key thing for sleep is that it calms down your brain cells (The Neuroprotective Effects of Melatonin: Possible Role in the Pathophysiology of Neuropsychiatric Disease) and allows your body to clear out rubbish created during the day.
Melatonin is created in a number of different places in the body, but what matters for sleep is the Pineal Gland. The Pineal Gland injects melatonin directly into the third ventricle of the Cerebral Spinal Fluid (CSF). Melatonin can pass over the blood brain barrier so as the CSF is renewed from blood serum (it swaps over about 20% an hour) then Melatonin comes out of the CSF into the blood. What is important about this is that the concentration in the Third Ventricle that goes into the brain is much higher than in the blood (I have seen various reports of this with factors between 5 and 20). Hence if you want to get melatonin into the Third Ventricle so it can help with sleep you need a lot more than is normally found in the blood. Another issue with Melatonin is that it has a very short half life (about 30 mins). Hence if you take Melatonin to increase the level in your blood it won't last long. What I find is that it takes between an hour and 90 minutes for melatonin that I take to have an effect on sleep. First it has to get into the blood and then from there into the CSF. Also when I am quite drunk it does not work.
There is another issue which is there is a feedback loop in the blood which switches off the pineal gland when melatonin hits a certain level. I recommend being very careful about trying melatonin as it can be quite dramatic when first tried. However, Melatonin is not in my view something to take when going to bed. Instead it is something to take when you have middle insomnia (when you wake up in the middle of the night). What I try is some which is swallowed and delayed and at the same time some dissolved under my tongue. The idea is to spread out keeping up the blood serum level so that it maintains the level in the CSF for longer.
I do think, however, that Melatonin helps to retrain the sleeping systems into sleeping better. For many people the pineal gland gets calcified over time. That may reduce the production of melatonin. My own experience is that if I extend sleep using Melatonin on one night it can assist for the next two nights as well which may be a retraining effect.
A good review of Melatonin Measuring sleep and keeping records
Because a number of things affect sleep on more than one day it is quite difficult to work out what is going on. Also if you have a bad night's sleep you will have more sleep pressure and sleep better on the following night. Hence if you wish to work out what works best you need to approach it like a scientific experiment and measure things and keep records. I personally like having blood pressure for night and morning, weight and using a fitbit for sleep measurements. The fitbit is not perfect, but it gives some useful information which can be used to see if sleep is getting better or worse. As a wrist monitor it does not interfere with sleep and although the specialists think it is not good enough it is good enough for me. When you keep records as to what supplements you take, what you drink and what you eat then you can see what is having an impact. We found that melatonin rapidly and reversibly enhanced I(GABA) in a dose-dependent manner, with an EC50 of 949 μM. Melatonin markedly enhanced the peak amplitude of a subsaturating I(GABA) but not that of a saturating I(GABA). Interestingly, melatonin was effective only when GABA and melatonin were applied together.
Thoughts 30/10/21
Further to my video I am pretty certain that Melatonin's GABAergic effects are through the Cerebral Spinal Fluid into the Hypothalamus. It is also quite possible that Melatonin is metabolised in the brain. Both of those things give rise to a greater need for Melatonin than is generally assumed. The inner CSF–brain barrier: developmentally controlled access to the brain via intercellular junctions indicates that Melatonin with a molecular weight of 232.28 would have no difficulty getting into the neurons from the CSF.
An interesting research paper that looks at Melatonin demethylating the epigenome in lead poisoned radishes Similar in grapes similar in pig clones here preventing demethylation Melatonin alleviates adipose inflammation through elevating α-ketoglutarate and diverting adipose-derived exosomes to macrophages in mice Paper about dietary melatonin and health improvements
Look at Magnesium Supplements (note that some indigestion reliefs including magnesium)
Magnesium is another element which our cleaner diet today seems to not provide enough of. As a Supplement I find Magnesium Citrate and Magnesium Malate quite useful. It is worth being sensitive to the fact that many other things such as some indigestion pills include Magnesium Stearate. I think at times I have overloaded with Magnesium partially as a result of taking too many indigestion pills. That caused sleep maintenance problems as well. However, I think getting a good balance between Magnesium and Calcium (Vitamin D) is helpful.
If you take magnesium and think it makes your farts more pungent in fact that is probably not true. It is more likely that your sense of smell has improved. I only take one Mg Malate pill a day. I need to run some tests with varying amounts. The packet is not that clear as to whether this is 300mg malate or 900mg malate, but in the end the experimentation runs at numbers of capsules.
Paper that suggests extra Vitamin D reduces magnesium What is key is that Magnesium is needed to metabolise D3. Hence taking D3 without Magnesium is an issue (as well as taking it without K2). Someone who says take a lot of magnesium
Vitamin B6
I am currently experimenting with B6 taken with Magnesium to see if that assist with the creation of endogenous melatonin.
Other supplements
I take other supplements on either a twice a week basis or daily.
In 2016, however, I started to keep some records as to particularly what I was drinking, but also my blood pressure and heart rate on waking and going to sleep. I then decided to put some serious effort into improving my sleep patterns. I am pleased to say that I have made good progress with improving sleep and getting rid of insomnia. I have decided to write this blog post. In part to enable me to structure the medical research that I have collated and in part because I have found that people are unsurprisingly often quite interested in my experience in this area. Hence I will write this partially from the point of view of suggestions as to things to do which can improve sleep and health more generally.
What I intend to do is to update this particular post. I am not medically qualified and all I am writing about are my own experiences and a collation of information I have found on the internet. Hence I am not giving medical advice. Different people are different. I am quite big being 6 foot 2 and weighing between 21 stone (130kg) and a target of 14-16 stone (98-101 kg). I am currently 105kg, but my weight is reducing. (as a result of eating less intentionally). If people take dietary supplements it will vary which ones help people and people will suit different quantities. For example Vitamin D is fat soluble and if you are obese - as I was until recently - you need to take more to have the same effect.
Hence I would suggest that you read this and use it as a basis of suggestions for research rather than a recipe for improving health and getting rid of or reducing insomnia. Talking to your medical practitioner about the suggestions before taking anything is worth considering once you have done your own research.
Two youtube videos
Insomnia harms health
There are many ways in which insomina harms health. Hence if you reduce insomnia you are likely to have other health improvements. My own blood pressure and resting heart rates have come down. Some of this is as a result of losing weight, but the effect of reducing insomnia also helps. The body uses sleep to repair itself hence if people are not sleeping well that process does not work properly. I will focus in this post on reducing insomnia, but that is also about improving health.
Many people are used to a situation where they are really tired in the afternoon and often need a nap. My experience is that I have been able to improve my sleep patterns such that I can go through the day being effective and sleep only at night.
CBT should always be tried
CBT is Cognitive Behaviour Therapy. That is really a fancy title for improving what you do. Part of this is also known as Sleep Hygiene. People who are reading things on the internet are likely to have seen these sort of things listed elsewhere. However, here is a list.
- Make sure the bedroom is really dark and quiet when the lights are switched off.
- Try to have regular sleep times even at the weekend.
- Avoid blue light during the night. That means not having a TV in the bedroom and not looking at your mobile phone. You can get software for mobile phones that reduces the amount of blue light, but blue light tends to get rid of melatonin. Melatonin is what keeps you asleep (it is generated by the pineal gland). Systematic review of light exposure impact on human circadian rhythm will give you more details of how bad blue light (wavelength 460nm worst effects at 424nm) can be.
- Best not to lie in bed awake trying to sleep. I find that if I wake up during the night (and cannot quickly get back to sleep) it is best to reset my pineal gland by getting up and potentially doing some work, but then going back to bed after about an hour. (The paper linked to above says that melatonin can recover from computer light in 15 mins.) If this is likely to happen it does mean allowing enough time for the sleep process to be awake for a couple of hours during the night. There are those that argue that biphasic sleep (waking up and then going back to sleep) is natural. It is a nuisance because you need to allow more time for sleep including a period awake, but it can work.
- Keep off the booze. I like the taste of many drinks and getting drunk and I still do that from time to time. However, although getting drunk helps to fall asleep you then wake up in the middle of the night. It can be very difficult to get back to sleep after that and it can hence damage the next day.
- Keep off the sleeping pills. Anti histamines such as Diphenhydramine don't enable the best sort of recuperative sleep and I avoid those.
- Avoid napping during the day. A bad insomnia routine involves having problems getting to sleep (latency) or waking up in the middle of the night (maintenance) and then having to sleep in the afternoon. This then reduces "sleep pressure" which means having problems getting to sleep and waking up in the middle of the night.
- I will update this later when I have some time, but other thoughts include: Caffeine reduction (the half life is 6 hours and tea also has caffeine in it), If you are worrying about something write it down (and the proposed solutions) to clear your mind of worries, there are arguments as to what extent your bedroom should be cool, I think cool rather than cold, make sure your bedding is comfortable and you lie in a good position, having exercise during the day is a good idea, but avoid 3 hours before going to bed, a ritual about sleep is a good thing including relaxing beforehand listening to music rather than the news perhaps doing breathing exercises, avoid eating too late in the evening, having bright sunlight in the morning is a good thing. Another thing that is suggested and tried at time is to try to remain awake in bed without using external techniques (ie no pinching, or poking yourself). This is called paradoxical intention and has been found to work for some people. A slightly different version of this is Intensive Sleep Retraining that is normally done in a lab, however. Kundali Yoga is a further option as is tai chi. (For further information see Cognitive and Behavioral Treatment Options for Insomnia by Matthew R. Ebben, PhD and Mariya Narizhnaya, MA).
Warning: Vitamin D
Some people have a genetic mutation which means they do not handle Vitamin D well. If you think you may fall into this category get it checked. Here is a media story about Baby deaths mystery from 1930s solved by researchers finding 'abnormal' gene shape link to vitamin D side-effects
Make sure you have enough Vitamin D
People are I think becoming more aware of the importance of Vitamin D. From a sleep point of view, however, you need to be careful not to take Vitamin D too late in the day. Vitamin D goes through an interesting metabolic cycle where it first gets converted (Vitamin D Metabolism, Mechanism of Action, and Clinical Applications) to 25OHD (Calcifediol) in the liver and then the kidneys convert it to 1,25-dihydroxyvitamin D (1,25(OH)2D - Calcitriol) which is a hormone and has the main effects. There are many reports that if you take it in the afternoon or evening then it holds back sleep. Similarly if you are using a 311nm Ultra Violet light or even the Sun to generate your vitamin D then it is best not to do this in the evening before going to sleep. The Sun is quite helpful in this in that the Sun has been well trained not to shine brightly just before you should be sleeping. However, I would not suggest switching on a UV light in the evening. I have not found a paper which studies this formally, but I have seen lots of papers talking about this.
Vitamin D does a lot of other things. You do need to be careful not to take too much vitamin D. (Vitamin D Toxicity–A Clinical Perspective) However, the example of someone who got too much calcium in their blood from about 10,000 iu a day was from someone who was also sunbathing. In the winter when there is not enough UVB around (particularly in England) people do need Vitamin D. The NHS in England recommends 400iu, in Germany they recommend 800iu. I personally was taking 3000iu a day which I originally wrote this, but remember different people will need different amounts. I later moved to 1000iu a day because I lost about 15 more kg plus possibly 1000-2000 IU in 25OHD. Vitamin D is fat soluble so if you take it in oil then perhaps you get about 30% more than taking the same quantity of Vitamin D in tablet form.
What I find if I have too much vitamin D (and that is not hypervitaminosis D,but just too much on the day or late in the day) is that I have problems with sleep maintenance at about 2am. I find that if I take a relatively heavy dose say 24,000 iu (iu being the measurement that allows comparison of different types of vitamin) then it can cause sleep maintenance problems for a couple of days. My guess is that this is because it takes a bit of time to process it into 250HD, but that's just a guess. However, if I have enough vitamin D and don't take it for a day things work OK until the vitamin D levels go down.
The metabolism of Vitamin D is really quite complex and cannot be treated as having a half life particularly as it converts into different things. However, it will hang around for a while so if you end up taking too much it won't go away by just stopping. If you really have overdone it and have hypercalcaemia (too much calcium) you may need some medical treatment.
Some reading: LARGE, SINGLE-DOSE, ORAL VITAMIN D SUPPLEMENTATION IN ADULT POPULATIONS: A SYSTEMATIC REVIEW of 30 papers looking at a really large dose Safety of 50,000-100,000 Units of Vitamin D3/Week in Vitamin D-Deficient, Hypercholesterolemic Patients with Reversible Statin Intolerance The authorities tend to recommend a maximum of 4,000 IU per day. I have noticed issues with sleeping at 6,000iu per day and I think that is a metabolic issue and not something that would lead to hypervitaminosis, but I am not a medic. What I think is happening is that there is a high level of unprocessed Vitamin D floating around in the blood. I have seen a paper that indicates that this can cause problems. Until the Liver has switched it to 25OHD it can be a bit of a nuisance. It is going to take some time for the liver to process it.
Hence with Vitamin D. Remember to look at taking it in the morning. That also means not using a UV light at night. If you are sunbathing in the summer you won't need as much of a supplement (or any) compared to the winter.
This is a particularly interesting paper Evaluation of vitamin D3 intakes up to 15,000 international units/day and serum 25-hydroxyvitamin D concentrations up to 300 nmol/L on calcium metabolism in a community setting which looks at higher doses of D3. It concludes "Serum 25(OH)D concentrations up to 300 nmol/L were found to be safe." It seems that the body safely stores Vitamin D in 25OHD form (which is logical if it comes in mainly during the summer). However, my own experimentation concludes that there is a limit on the rate at which D3 is converted to 25OHD (which is obviously going to be the case) which would argue for a daily supplementation rather than weekly.
This article medcape Says 25OHD has a half life of 15 days and the hormone has 15 hours. Alternatively this article Vitamin D has longer than expected half-life: Tests may not show true 'plateau' says it is two months. I think actually both are wrong. The conversion to the hormone in the kidneys is controlled by feedback systems. Hence it would not so much have a half life like a radioactive nucleus, but intead a consumption rate primarily perhaps also linked to a half life, but dominated by a consumption rate. One would assume that the consumption rate would vary. Hence if people get a really high 25OHD it will take quite a while to get rid of it (hence the argument not to overdose on D3).
There can be a recommendation that if taking Vitamin D supplements it is best not to also take calcium supplements but to get additional calcium via the diet if needs be. Mobilising vitamin D from adipose tissue: The potential impact of exercise is an interesting article that also looks at the storage of D3 in fat tissue particularly for fat people. It makes the point that potentially many years of the RDI can be stored and potentially it can be recovered by exercise. People can overdose on vitamin D if they have kidney problems which restrict conversion of 25OHD to the hormone or on 10,000 iu a day in other circumstances. A key point about Vitamin D is to tell any medical professionals if you are taking it so they can take that into account for a diagnosis if there are any issues to look at.
Further on the metabolites
It is, of course, possible to take 25OHD directly or the hormone itself. I would discourage people from taking the hormone itself as the body manages carefully the level of hormone that is available. However, there are potentially advantages in taking 25OHD. This study looks at the options: Cholecalciferol or Calcifediol
Quoting: "Indeed, when using dosages ≤ 25 μg/day, serum 25OHD increased by 1.5 ± 0.9 nmol/l for each 1 μg cholecalciferol, whereas this was 4.8 ± 1.2 nmol/l for oral calcifediol." So let us say from this given 1 μg of D3 is 40iu, 1 μg of Calcifediol is about 120iu. Otherwise I have used figures of 200iu for 1 μg of Calcifediol. (One nmol/L = 0.4 ng/mL) Alternatively to take serum 250HU up by 10 nmol/l. Normal range for serum level is quoted as various figures, but between 30 and 60 ng/m is one.
Hence using these figures (and remembering different people will respond differently) to move serum level by 10ng/ml requires a movement of 25nmol/l, which would require 17μg of d3 or 5.20 μg of Calcifediol ie about 600-700iu.
A systematic review and meta-analysis of the response of serum 25-hydroxyvitamin D concentration to vitamin D supplementation from RCTs from around the globe It gives a sort of answer. Perhaps stating take a bit more than the calculation above. Similarly with this Vitamin D Metabolism and Guidelines for Vitamin D Supplementation (2020 - Review) From the review:"Studies have shown that dosing with vitamin D3 required in the order of 150–180 d to reach something approaching a steady state. During the study period, concentrations of 25(OH)D increased with a slope (change/dose) of 0.70 nmol/L (0.28 ng/mL) for each 40 IU (1 μg) of vitamin D3 input, in subjects with mean baseline 25(OH)D value of 70.3 nmol/L (28.1 ng/mL).48 In an earlier study by the same authors, the change in 25(OH)D over the study period was 1.23 nmol/L (0.49 ng/mL) for each 100 IU (2.5 μg) of vitamin D3 input. In a summary of 13 studies carried out during the period 1977–1996, the increase in 25(OH)D varied from 1.47–8.75 nmol/L (0.59–3.5 ng/mL) per 100 IU (2.5 μg) of oral vitamin D intake.38 In subjects with an average 25(OH)D concentration of 47 nmol/L (18.8 ng/mL), treatment with vitamin D at concentrations of 1000 IU/d (25 μg/d) or 4000 IU/d (100 μg/d) increased serum 25(OH)D over 3 m to 69 nmol/L (27.6 ng/mL) and 96 nmol/L (38.4 ng/mL) respectively.49 In a review of 49 studies, authors conclude that the ‘rule of thumb’ is 5.0 nmol/L (2 ng/mL) increase of 25(OH)D for each 100 IU/d (2.5 μg/d) of ingested vitamin D.50 In a review of 76 trials published from 1984 to 2011 the average increase was 1.95 nmol/L (0.78 ng/mL) per 40 IU (1 μg) of vitamin D3 supplement per day.51 A summary suggests that trials that used similar doses could obtain changes in 25(OH)D that can vary 3–4-fold. A mean slope of 0.66 nmol/L per 40 IU/d (0.26 ng/mL per μg/d) was reported by Aloia et al.41 The individual slopes ranged from 0.15–1.49 nmol/L (0.06–0.60 ng/mL), virtually a 10-fold increase. Investigators either report the same slope for different dosage concentrations48 or a variable response dependent on the IU of vitamin D intake.41 " From this to get an additional 10ng/ml would require 1429, 889, 678-131 iu. I think part of the difficulty here relates to deficiency vs sufficiency vs plenty and part the difference between individuals.
There are three commercial versions of 25OHD that can be obtained I think they are all on prescription. These are Hidroferol, Dedrogyl and Rayaldee. Rayaldee has delayed release and is really quite expensive. I have no further knowledge of Hidroferol, but Dedrogyl seems to be worth a look. The advantage of taking 25OHD directly is that you don't end up with an excess of D3 which in my experience is not a nice thing as it can cause sleep problems. Roche produce Rocaltrol which appears to be available in the UK, but seems to be a really low dose (ie 0.25mcg or 0.5mcg a 10th or 20th of the single drop of 5mcg Dedrogyl).
This paper looks at whether taking a large amount of 25OHD can be counter productive in getting rid of vitamin D (inter alia) However, this compared single delayed release to bolus rather than daily. In a sense this fits with the idea that the serum level would go right up and upregulate (switch on) the CYP24A1 gene which generates an enzyme that switches 25OHD to 24,25(OH)₂D.
This paper looks at high levels of 25OHD and some being catabolised into 24,25(OH)₂D. The interesting question is whether that then has physiological functions or whether it just gets excreted having been metabolised a bit more. This comes into the debate as to whether there are three levels of vitamin d: Deficient, sufficient and plenty. In Plenty mode it gets used up doing other things (possibly via 24,25(OH)₂D), but if it pops back into sufficient then the essential functions are maintained. The hormone dihydroxyvitamin D (1,25(OH)₂D aka calcitriol) tends to be kept at pretty constant levels given enough 25OHD.
This means there is some uncertainty about how to take 25OHD to increase serum levels. Taking delayed release is one option. Another option is to take it a few times a day. Probably taking a big wodge at one time will cause some 25OHD to be converted to 24,25(OH)₂D. That may be a good thing and it may be a bad thing or it may be just futile. Linus Pauling Institute on Vitamin D
Some people say to take K2 M7 with Vitamin D3 Coffee man on D3 Looking at these articles it clearly helps to take some form of Vitamin K with Vitamin D, but that is a complex issue about which I have written a Separate page
Look at anthocyanins (not as bad as it sounds)
Anthocynanins are a type of chemical that can be used to make plants have a particular range of colour. I have found that Pomegranate juice, Blackberries and Black Turtle Beans (which can be found in Marks and Spencer 3 bean salad) all help with sleep. There is also research that recommends Tart Cherry juice. The common feature of these is that they all have anthocyanins in them. I have not as yet, however, found any research that substantiates this beyond my own experimentation.
There are various studies into heating anthocyanins Thermal and pH degradation kinetics of anthocyanins in natural food colorant prepared from black rice bran Effects of Cooking Methods on Anthocyanins and Total Phenolics in Purple‐Fleshed Sweet Potato In essence, however, cooking anthocyanins runs the risk of degrading them to not be effective. Hence best to eat the blackberries without cooking them first.
Consider melatonin
Melatonin is a really interesting hormone. In a sense Melatonin is the hormone of the night and Vitamin D is the hormone of the day. Melatonin does a lot of things. However, a key thing for sleep is that it calms down your brain cells (The Neuroprotective Effects of Melatonin: Possible Role in the Pathophysiology of Neuropsychiatric Disease) and allows your body to clear out rubbish created during the day.
Melatonin is created in a number of different places in the body, but what matters for sleep is the Pineal Gland. The Pineal Gland injects melatonin directly into the third ventricle of the Cerebral Spinal Fluid (CSF). Melatonin can pass over the blood brain barrier so as the CSF is renewed from blood serum (it swaps over about 20% an hour) then Melatonin comes out of the CSF into the blood. What is important about this is that the concentration in the Third Ventricle that goes into the brain is much higher than in the blood (I have seen various reports of this with factors between 5 and 20). Hence if you want to get melatonin into the Third Ventricle so it can help with sleep you need a lot more than is normally found in the blood. Another issue with Melatonin is that it has a very short half life (about 30 mins). Hence if you take Melatonin to increase the level in your blood it won't last long. What I find is that it takes between an hour and 90 minutes for melatonin that I take to have an effect on sleep. First it has to get into the blood and then from there into the CSF. Also when I am quite drunk it does not work.
There is another issue which is there is a feedback loop in the blood which switches off the pineal gland when melatonin hits a certain level. I recommend being very careful about trying melatonin as it can be quite dramatic when first tried. However, Melatonin is not in my view something to take when going to bed. Instead it is something to take when you have middle insomnia (when you wake up in the middle of the night). What I try is some which is swallowed and delayed and at the same time some dissolved under my tongue. The idea is to spread out keeping up the blood serum level so that it maintains the level in the CSF for longer.
I do think, however, that Melatonin helps to retrain the sleeping systems into sleeping better. For many people the pineal gland gets calcified over time. That may reduce the production of melatonin. My own experience is that if I extend sleep using Melatonin on one night it can assist for the next two nights as well which may be a retraining effect.
A good review of Melatonin Measuring sleep and keeping records
Because a number of things affect sleep on more than one day it is quite difficult to work out what is going on. Also if you have a bad night's sleep you will have more sleep pressure and sleep better on the following night. Hence if you wish to work out what works best you need to approach it like a scientific experiment and measure things and keep records. I personally like having blood pressure for night and morning, weight and using a fitbit for sleep measurements. The fitbit is not perfect, but it gives some useful information which can be used to see if sleep is getting better or worse. As a wrist monitor it does not interfere with sleep and although the specialists think it is not good enough it is good enough for me. When you keep records as to what supplements you take, what you drink and what you eat then you can see what is having an impact. We found that melatonin rapidly and reversibly enhanced I(GABA) in a dose-dependent manner, with an EC50 of 949 μM. Melatonin markedly enhanced the peak amplitude of a subsaturating I(GABA) but not that of a saturating I(GABA). Interestingly, melatonin was effective only when GABA and melatonin were applied together.
Thoughts 30/10/21
Further to my video I am pretty certain that Melatonin's GABAergic effects are through the Cerebral Spinal Fluid into the Hypothalamus. It is also quite possible that Melatonin is metabolised in the brain. Both of those things give rise to a greater need for Melatonin than is generally assumed. The inner CSF–brain barrier: developmentally controlled access to the brain via intercellular junctions indicates that Melatonin with a molecular weight of 232.28 would have no difficulty getting into the neurons from the CSF.
An interesting research paper that looks at Melatonin demethylating the epigenome in lead poisoned radishes Similar in grapes similar in pig clones here preventing demethylation Melatonin alleviates adipose inflammation through elevating α-ketoglutarate and diverting adipose-derived exosomes to macrophages in mice Paper about dietary melatonin and health improvements
Look at Magnesium Supplements (note that some indigestion reliefs including magnesium)
Magnesium is another element which our cleaner diet today seems to not provide enough of. As a Supplement I find Magnesium Citrate and Magnesium Malate quite useful. It is worth being sensitive to the fact that many other things such as some indigestion pills include Magnesium Stearate. I think at times I have overloaded with Magnesium partially as a result of taking too many indigestion pills. That caused sleep maintenance problems as well. However, I think getting a good balance between Magnesium and Calcium (Vitamin D) is helpful.
If you take magnesium and think it makes your farts more pungent in fact that is probably not true. It is more likely that your sense of smell has improved. I only take one Mg Malate pill a day. I need to run some tests with varying amounts. The packet is not that clear as to whether this is 300mg malate or 900mg malate, but in the end the experimentation runs at numbers of capsules.
Paper that suggests extra Vitamin D reduces magnesium What is key is that Magnesium is needed to metabolise D3. Hence taking D3 without Magnesium is an issue (as well as taking it without K2). Someone who says take a lot of magnesium
Vitamin B6
I am currently experimenting with B6 taken with Magnesium to see if that assist with the creation of endogenous melatonin.
Other supplements
I take other supplements on either a twice a week basis or daily.
- General Vitamins - I take Solvar's VM-2000 twice a week. I think it is quite good, but it should not be taken daily because doing this would undermine the body's own immune system by being too supportive. That is secondary information, however.
- Fish Oil - I take this twice a week it avoids aches and pains. I know this works because when I have stopped taking it I get aches and pains that go away after a bit.
- Zinc - I take 40mg twice a week. I think people need to be careful with Zinc. It can help the immune system, but some people react badly to the 40mg tablets. I have no proof that it works myself, however.
- Boron - I take 3mg daily to avoid arthritis not that I have had any signs of arthritis. It seems to be helpful. However, I don't have any direct proof.
Other supplements needs further consideration
I have looked at some other supplements over time, but I have not managed to get any successful results from experimenting with them. The word "successful" I take as being either finding something positive or negative from taking them. In part I am limited by only being able to do at a maximum one experimental test each day (having only one experimental subject). Also when the experimental subject gets drunk it skews any results. However, there are other supplements that may have some effect that I wish to try out over time.- Selenium
- Theobroma
Quantitative analysis of the whole-body metabolic fate of branched chain amino acids Possibly reduction in insulin resistance also reduces the serum levels of BCAAs. Also: "BCKDH, however, is also expressed and active in most tissues including muscle, white adipose, kidney, and brain". Put down the protein shake: Variety of protein better for health Effect of an oral branched chain amino acid-enriched snack in cirrhotic patients with sleep disturbance Branched-chain amino acid in chronic renal failure patients: respiratory and sleep effects Branched chain amino acids impact health and lifespan indirectly via amino acid balance and appetite control The role of tryptophan in fatigue in different condi tions of stress A randomized controlled trial: branched-chain amino acid levels and glucose metabolism in patients with obesity and sleep apnea Branched chain amino acids, aging and age-related health Metabolomics in Sleep, Insomnia and Sleep Apnea The Human SLC7A5 (LAT1): The Intriguing Histidine/Large Neutral Amino Acid Transporter and Its Relevance to Human Health "In general, BCAAs are transported through the blood–brain barrier via the L-type or large amino acid transporter 1 (LAT1) to serve as a major nitrogen source for the brain"
Other AAs QuestioThe Sleep-Promoting and Hypothermic Effects of Glycine are Mediated by NMDA Receptors in the Suprachiasmatic Nucleus
Other AAs The Sleep-Promoting and Hypothermic Effects of Glycine are Mediated by NMDA Receptors in the Suprachiasmatic Nucleus article needs getting title
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Glycine is inhibitary article needs getting title
Vitamin D question of kidney stones
Other issues
Work in progress
Other useful info: Carvacrol Carvacrol etc Oral Bacteria Cinnemaldehide Antimicrobial Properties of Plant Essential Oils against Human Pathogens and Their Mode of Action: An Updated Review (2016) Anti Bacterial Table- EO Apricot Kernel Extract and Cyanide
Please note that I am not associated with any of these links (apart from the one to another page on my blog) nor do I endorse anything that I link to. Some links contain material that I think is wrong although obviously the majority is information I think is right.
Please also note that I am updating this from time to time as I find new things, but it may not read that well until I do a review.
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