melatonin

Seasonal thyroid fluctuations, biology and mood

 As you may have read from previous blogs, the thyroid, its pituitary stimulator - thyroid stimulating hormone (TSH) and the other thyroid hormones are heavily influenced by environment, nutrition and stress. Additionally these hormones can present as normal when relied upon purely by biochemical analysis from the blood. The seasons, differing temperatures, light exposure and effects of hibernation hormones and neurotransmitters can also be a key factor in the expression of adequate energy, organisation and coherence of an individual’s biology. We get sick more so in winter when our function is suppressed and the immune system is called upon to mount a response.

Tromp.png

S.W. Tromp Biometerology 1967.

“ The yearly influenza peak in the Netherlands, around February. Which may be related to the usually low humidity and wind-speed in this period, but which effect is probably accelerated by the decreased thermoregulation efficiency of the body as a result of the preceding cold months and the accompanying changes in the physico-chemical state of the blood such as y-globulin level.”

 Ambient temperature can have a significant effect on TSH production in as much as a colder environment increases TSH and warmer temperatures decrease TSH production and thyroid requirement. Observations have suggested a biphasic seasonal nature of TSH secretion, with increased TSH readings during winter time suggesting what could be a functionally hypothyroid or subclinical hypothyroidism which resolved during the summer months (Kim et al., 2013). As this stress increases throughout longer days of darkness, organisational hormones decrease, whilst stress hormones increase. If chronic enough, or in an unstable biology, stress can decrease the accuracy of TSH to predict a low thyroid state

 Light, both red and ultraviolet (UV) are well-known modulators of immune function, metabolism and mitochondrial production of energy or  adenosine triphosphate (ATP) (Wong-Riley et al., 2005) (Karu, 2010). These aspects of sunlight, exert their influence via enhancement of aerobic metabolism (at cytochrome c) and immunity enhancing via infra-red (NIR) and vitamin D synthesized by UV respectively.  The variation in light exposure as a consequence of daily sleep, darkness and seasonal variations present relationships that may explain the secretory patterns of TSH in healthy subjects. More than 100 years ago, thyroid function could be suggestively viewed via uptake of thyroid iodine levels in seasonal variations. (Fenger and Siedell 1913). Thyroid iodine levels rose during the summer in sheep, pigs and cows and decreased during the winter reflecting the variations in the need for TSH/TH production in healthy organisms. 

Seasons, Thyroid and Mood

 Depression is a known symptom of hypothyroidism and some studies have highlighted the need for a lower TSH value in the presence of depressive symptoms (Talaei, Rafee, Rafei, & Chehrei, 2017) (Hage & Azar, 2012). The former authors suggest a cut-off value of 2.5 mU/L for TSH as a point for treating hypothyroidism, which highlights the need for assessing symptoms as part of an effective strategy for diagnosing hypothyroidism. This compares to the attitude taken to expecting mothers where values should be decreased to compensate for hypothyroid states but in reality should be applied across the board.

 Relationships concerning seasonal variations of mood are well documented and decreased Beck mood scores are associated with the shorter days of winter (Harmatz et al., 2000). Seasonal affective disorder (SAD) may be a reflection of the increase in serotonin and melatonin and depression of thyroid hormone, which are increased by shorter days and in mammals are associated with hibernation. This aspect seems to be lost on those treating transient depressed states but light therapy does appear to be taken seriously these days. I would encourage anyone wanting more information on serotonin and mood to check out the extremely well written blog Against Utopia.

 As days become shorter and light exposure is decreased, influencing cellular function and metabolism negatively. The extended effects of melatonin from the shorter days can antagonise TSH secretion via its inhibitory action on TH, increasing prevalence throughout winter. Whilst fluctuations in TSH levels in response to seasonal changes are well-known to occur, these fluctuations are also under the influence of the nutritional and environmental factors that can suppress TSH values.

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Wake me up when it’s spring?

Violent suicides increase with the onset of spring from March to May. I was trying to think why this might occur? After speaking to a friend recently about depression, they said that holding onto the feelings of a blanketed, safe, dark environment by being it home (in a somewhat hibernation like state), and gorging on boxsets or podcasts was easy to do and a comfort. I wonder if the shorter phases of darkness and increased light remove that blanket of increased serotonin and melatonin and the light itself might become a stressor that takes away that comfort? Those most at risk might explain this seasonal increase in suicides?

Ray Peat (1997) has discussed various aspects of stressors such as darkness, oestrogen-cold sensitive enzymes and nutritional factors affecting endocrine systems, adding an interesting perspective on hormone production and relationships with temperature changes (Peat, R. and Soderwall, 1972) (Peat, 1997)(Peat, 1972).

In states of undetectable SCH mediated by the stress, a hypothermic state may stimulate the adrenal stress system to compensate for a low-metabolic and decreased temperature state.  Activated compensatory stress response pathways may explain poorly detected hypothyroid patients. Decreased metabolic rate, lowered temperature and pulse rate are well-known signs of hypothyroidism. β adrenergic mechanisms involving increased catecholamine production such as adrenaline and noradrenaline (NA) can increase Tb and RHR. In my previous blog on body temperature, I explained how low temperature can be indicative of low thyroid function when blood tests appear normal.

  

References:

Hage, M. P., & Azar, S. T. (2012). The link between thyroid function and depression. Journal of Thyroid Research. http://doi.org/10.1155/2012/590648

Harmatz, M. G., Well, A. D., Overtree, C. E., Kawamura, K. Y., Rosal, M., & Ockene, I. S. (2000). Seasonal variation of depression and other moods: A longitudinal approach. Journal of Biological Rhythms. http://doi.org/10.1177/074873000129001350

Karu, T. I. (2010). Multiple roles of cytochrome c oxidase in mammalian cells under action of red and IR-A radiation. IUBMB Life. http://doi.org/10.1002/iub.359

Kim, T. H., Kim, K. W., Ahn, H. Y., Choi, H. S., Won, H., Choi, Y., … Park, Y. J. (2013). Effect of seasonal changes on the transition between subclinical hypothyroid and euthyroid status. Journal of Clinical Endocrinology and Metabolism. http://doi.org/10.1210/jc.2013-1607

Peat, R. and Soderwall, A. L. (1972). Estrogen stimulated pathway changes and cold -nactivated enzymes. Physiol Chem Phys, 4((3)), 295–300.

Peat, R. (1997). From PMS to Menopause: Female Hormones in context.

Peat, R. (1999). Thyroid Therapies, Confusion and Fraud. Retrieved from www.raypeat.com/articles/articles/thyroid.shtml

S.W., Tromp. (1967). Biometeorology, iia and b. Symp. Publ. Div. Pergamon Press (Oxford).

Talaei, A., Rafee, N., Rafei, F., & Chehrei, A. (2017). TSH cut off point based on depression in hypothyroid patients. BMC Psychiatry, 17(1). http://doi.org/10.1186/s12888-017-1478-9

The Armour Laboratories. (1945). The Thyroid Gland and Clinical Application of Medicinal Thyroid. Armour Laboratories.

Wong-Riley, M. T. T., Liang, H. L., Eells, J. T., Chance, B., Henry, M. M., Buchmann, E., … Whelan, H. T. (2005). Photobiomodulation directly benefits primary neurons functionally inactivated by toxins: Role of cytochrome c oxidase. Journal of Biological Chemistry. http://doi.org/10.1074/jbc.M409650200

 

Sleep, stress, sugar. Eat sugar for better sleep.

Onset of sleep

Onset of sleep

Can you improve sleep and decrease stress by eating sugar for better sleep? If you put sleep, stress and sugar in the same sentence, most people think they have already put the three together with something like; too much sugar causes stress and affects your sleep. If you read on you should find yourself advantageously aware of sleep biology and why consuming sugary foods before sleep, and indeed if you wake up are the answer for a deeper nights sleep.

Ah a good nights sleep. You remember one of those don’t you? As a father to 3 children I have had my fair share of sleepless nights but a recent 11 hour sleep whilst my kids slept for 12 hours, recently reminded me of why everyone should strive for better sleep and the common approaches that people tend to fail to implement. A couple of years ago I studied a short course on the neurobiology of sleep with the University of Michigan and I found it useful as it correlated with aspects of serotonin function that Ray Peat (7,8) had talked previously talked about.

Generalisations of sleep biology phases are:

Sleep latency - Getting your sorry arse to sleep

NREM sleep - Keeping your sorry arse asleep

REM sleep - Deep arsed sleep

Wakefulness - Wake your sorry arse up

One of the primary driving factors of the onset of sleep or sleep latency is the production of adenosine. Caffeine is a well-known antagonist of adenosine and therefore many a wise word about not drinking caffeine after 3-4 pm as it has a half-life of 6 hours are well heeded (yes I know there are some of you that metabolise caffeine really well after that time with no impact on sleep, STOP SHOWING OFF).  Avoiding caffeine though out the day isn’t necessary and caffeine is a widely mis-understand compound that shows many beneficial effects, if you follow the rules for its consumption.

Often there is much focus on the role of melatonin and sleep induction and structures like the suprachiasmatic nucleus and waking. Melatonin does indeed promote sleep but so does adenosine and I think the supplementing of melatonin misses key biological functions that induce sleep more effectively and without the negative effects associated with its use.

Serotonin and melatonin confusion

Sleep wake compounds

Sleep wake compounds

Just like the holistic health practitioner that suggests that coffee causes adrenal fatigue (it doesn’t but that’s another blog by itself), some practitioners recommend the use of 5HTP - tryptophan supplements (tryptophan converts to serotonin) for better sleep but this is misguided for the following reasons. It’s true that melatonin is a hormone of sleep and that it is derived from serotonin and that serotonin has a small but limited role in inhibiting the cholinergic system responsible for keeping you in an alert, thinking state. In the diagram below and born out of many studies is that serotonin is a powerful compound of wakefulness that synergises with histamine and the histaminergic system to bring you out of the deeper REM sleep, and start the process of waking you the hell up. The diagram from Brown et al (Brown, Basheer, McKenna, Strecker, & McCarley, 2012) highlights the complexities of the sleep wake compounds but also useful for highlighting serotonin's role (5HT) in the excitatory waking state. It’s also a great overview of the many areas and compounds that aren’t addressed in this blog. One thing that should become clear is that the neural structures controlling sleep are many and so are the interactions between hormones and other compounds of wakefulness. My advice below is not complete but merely a reflection of some of the simple changes that you can do (and which I have done with many clients) to create better sleep and recovery. 

Here are a few pointers on serotonin and melatonin.

  • Many people are aware of the fact that at least 95% of the body's serotonin is produced in the intestines - namely the enterochromaffin cells.

  • People associate serotonin as a hormone of calmness. 1) It’s not a hormone 2) well known side effects of serotonin excess are insomnia and anger.

  • Serotonin induces spasticity of the colons smooth muscle tissues

  • Eating excess muscle meats increases serotonin (as does eating poorly digestible foods), inflammation and can contribute to increased wakefulness by synergising with histamine.

  • Melatonin may be implicated in seasonal affective disorder due to increased levels in darker winter days. Sunglass wearing may pose similar issues (Alpayci, Ozdemir, Erdem, Bozan, & Yazmalar, 2012)

  • Supplementation with melatonin during the day can induce disruptive changes to fertility and also suppress thyroid hormone (Creighton & Rudeen, 1989).

  • Peak concentrations of thyroid stimulating hormone (TSH) occur at night and might be suggestive of thyroid hormone suppression induced by melatonin and other hormones. The pituitary responds by increasing TSH to bolster thyroid hormone supply.

Of course there are other compounds which include acetylcholine, GABA, oxycretin, histamine and many other areas of the central nervous system that could be mentioned but I have tried to stick to the mechanisms that can be changed and promote change in a short space of time.

If you find it hard to drift off, these are my suggestions as to why this might happen:

  1. You are eating foods that promote intestinal inflammation and increase serotonin and histamine.

  2. You are exposed to excess stimulus such as blue light, Wi-Fi or other source.

  3. Your blood sugar levels are not balanced and promote the stress hormones that liberate glucose from stored fats and proteins - adrenaline-glucagon-cortisol.

If you wake up at night the following might be also be an issue

  1. You are eating foods that promote intestinal inflammation and increase serotonin and histamine.

  2. Your blood sugar levels are not balanced and promote the stress hormones that liberate glucose from stored fats and proteins - adrenaline-glucagon-cortisol.

Point 2 may be a significant factor for many people and available efficient glucose production may be one of the most under-rated factors in both the onset of sleep and maintenance of sleep. Waking up to urinate at night is a feature of the diabetic like state. Poor blood sugar regulation requires, that instead of relying on blood and liver glucose stores, the stress response be relied upon to liberate energy from stored fats. This is an inefficiency that requires a stressed state. You should not be waking at night to go for a pee.

Morning Cortisol profile

Morning Cortisol profile

You can see from the average nighttime cortisol profile that cortisol generally starts to rise around 2 am, steadily increasing prior to the onset of waking. If your ability to regulate blood sugar levels is compromised this can increase the burden to blood sugar regulation and increase waking further. The REM phase of sleep uses a similar amount of glucose as the waking state.

Here are some useful tips that I use with clients to promote better sleep and recovery.

  1. Take a look at the previous post on resolving digestion issues. This helps to take away some of the factors related to serotonin and histamine excess.

  2. If you are exercising hard, low carb, busy parent or whatever form of stress and therefore don’t manage your blood sugar levels, you don’t manage your sleep. If you struggle getting to sleep a sweet drink like milk and honey (yes the old wives tale works like a charm). A glass of fruit juice with gelatin is also good. Any pattern with something with sweet with a little protein/fat is useful.

  3. Add some salt - increased stress burdens the adrenal glands, usually though thyroid hormone suppression. Salt is wasted in this state and so is magnesium. Salt spares magnesium, so adding a little salt also helps magnesium regulation.

  4. If you wake during the night. This can be common when trying to resolve these issues as liver function and hormone regulation take a little time to adjust. Therefore having something sweet by the bed can help to help you re-enter sleep. Squeezy honey tube or pouch of juice with straw I find useful so that the juice goes straight down rather than covering my teeth.

  5. I have often found that progesterone and thyroid play a key role in sleep and many clients have benefitted from resolving the states of low progesterone/thyroid, which may not have resolved with food alone.

  6. Optimal blood sugar regulation often starts with eating breakfast to decrease adrenaline, glucagon and cortisol (Jakubowicz et al., 2015)(Levitsky & Pacanowski, 2013). Drinking a kale smoothie or coffee on an empty stomach is not the best way to break your fast and set up the day.

  7. Of course aspects of sleep hygiene related to no phones, WI-FI etc goes without thinking and go as far as turning your router off at night.So armed with some facts that you can decrease stress and improve sleep by eating sugar in the right amount, you can go and experiment for yourself.

References:

  1. Alpayci, M., Ozdemir, O., Erdem, S., Bozan, N., & Yazmalar, L. (2012). Sunglasses may play a role in depression. Journal of Mood Disorders, 2(2), 80. http://doi.org/10.5455/jmood.20120529055051

  2. Brown, R. E., Basheer, R., McKenna, J. T., Strecker, R. E., & McCarley, R. W. (2012). Control of Sleep and Wakefulness. Physiological Reviews, 92(3), 1087–1187. http://doi.org/10.1152/physrev.00032.2011

  3. Creighton, J. A., & Rudeen, P. K. (1989). Effects of Melatonin and Thyroxine Treatment on Reproductive Organs and Thyroid Hormone Levels in Male Hamsters. Journal of Pineal Research, 6(4), 317–323. http://doi.org/10.1111/j.1600-079X.1989.tb00427.x

  4. Jakubowicz, D., Wainstein, J., Ahrén, B., Bar-Dayan, Y., Landau, Z., Rabinovitz, H. R., & Froy, O. (2015). High-energy breakfast with low-energy dinner decreases overall daily hyperglycaemia in type 2 diabetic patients: a randomised clinical trial. Diabetologia, 58(5), 912–919. http://doi.org/10.1007/s00125-015-3524-9

  5. Levitsky, D. A., & Pacanowski, C. R. (2013). Effect of skipping breakfast on subsequent energy intake. Physiology and Behavior, 119, 9–16. http://doi.org/10.1016/j.physbeh.2013.05.006

Online:

7. http://raypeat.com/articles/articles/serotonin-depression-aggression.shtml

8. http://raypeat.com/articles/articles/serotonin-disease-aging-inflammation.shtml

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