Melatonin Induces Circadian Phase Shift

The rise and fall of Melatonin induces Circadian Phase Shifts. Lower lengths of sunlight produces higher levels of melatonin.

Melatonin is primarily thought to be found only in the pineal gland. Melatonin is mainly produced in the pineal gland during the dark phase (night). Its secretion from the pineal gland has been classically associated with circadian and circanual rhythm regulation. However, melatonin production is not confined exclusively to the pineal gland, but other tissues including retina, Harderian glands, gut (400x more that pineal gland), ovary (200X more than gut), testes, bone marrow, thymus and bone marrow of humans and lens also produce it.

Most studies continue to erroneously view Melatonin as the “Sleep Hormone”. There is a dose–response relationship between light intensity or irradiance and melatonin production. A person’s prior light history has an impact on melatonin suppression or production.  Those suffering from autoimmune disease are more likely to seclude themselves in dark rooms. Unknowingly, increasing their melatonin production and increasing their immune system hyper-reactivity.

The sun rises later in the fall and winter and nightfall arrives much easier and this disrupts the timing of melatonin release some patients with autoimmune inflammation, Metabolic syndrome,,  Seasonal Affective Disorder, or producing disruptions to reproductive health and fertility. The seasonal fluctuations of melatonin coincides with the activity of the immune system, possibly allowing the body to anticipate and handle microbial threats more efficiently.

A circadian phase shift occurs when one or more daily circadian rhythms are disrupted in the fall and winter months as the days grow shorter and the nights are longer. Another phase shift occurs during the spring and summer as the opposite occurs. In these situations, one rhythm, e.g. enhance immune response, lags behind or pushes ahead of another rhythm, e.g. decreased Vitamin D production, results in increased inflammation.

After the Summer Solstice – More Melatonin is Produced

After the June Solstice (Northern Hemisphere) or the December Solstice (Southern Hemisphere), patients call because they are having more flairs or cytokine storms. They ask why they were feeling good and happy with their progress; and three to four weeks after the Solstice, they are regressing back to their original condition. It is due to the increased production of melatonin as the days get shorter. Yes, that little bit of increased production of melatonin causes that big of a change in their body.

WARNING: If the Summer solstice is rapidly approaching. Many people will start start having some flair ups. It amazes me how the melatonin produced by an additional six minutes of darkness after the Summer Solstice can provoke cytokine storms. The four supplements mentioned above will help dampen this affect.

PCOS Is Due to Increased Melatonin

Polycystic Ovarian Syndrome is due to increased Melatonin regulates a variety of physiological and pathophysiological processes including hypothalamic control of circadian rhythms, regulation of ovulation in women, and immune system stimulation, and the cardiovascular system. It has also been shown to influence cell differentiation where it can either stimulate or suppress cell division depending on melatonins concentration or the type of cell exposed to increased levels of melatonin.

Increased “Cell Differentiation”

In light of this, melatonin has been proclaimed to be a cure-all for everything from treating insomnia and cancer to acting as an anti-aging agent.

Most women with PCOS grow many small cysts on their ovaries. That is why it is called Polycystic Ovary Syndrome. Melatonin concentrations are higher in the fluid of large follicles (cysts) than in the small follicles (cysts) suggesting that increased melatonin in follicles (cysts) prior to ovulation may have an important role in ovulation processes.

Many women experience pain and increased symptoms during ovulation due to the spike in melatonin production. Often women call every month wondering what they did to cause a flair in their symptoms while others find that they may need to use ovulation test strips to help them know when ovulation will occur. The first question is: Where are you at in your cycle?

This would Infertility.

Increased melatonin levels are observed in women with PCOS, patients with dysfunctional reproductive organs, in patients of HPG Axis amenorrhea, and in anorexia nervosa.

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Hypothalamic Sampling Hormones Requires Blood Flow

Sampling of hormones (including the sex hormones) by the hypothalamus requires consistent blood flow. In the body, blood carries hormones released by endocrine glands and carries them to body parts that need them.

In parasympathetic withdrawal, diagnosis is usually considered adrenal fatigue. The volume of blood shifts from the muscles and brain to the central abdominal compartment. The blood flow to the brain is not stopped when this occurs. The flow is reduced and Poiseuille’s Laws come into play.

The circulatory system provides many examples of Poiseuille’s law in action—with blood flow regulated by changes in vessel size and blood pressure. Blood vessels are not rigid but elastic. Adjustments to blood flow are primarily made by varying the size of the vessels, since the resistance is so sensitive to the radius. This is done by the Abdominal Brain through the release of NeuroEndocrine transmitters, i.e. Serotonin – sero = “blood”, tonin = “pertaining to”.

A 19% decrease in flow is caused by a 5% decrease in radius of the blood vessels. The body may compensate by increasing blood pressure by 19%, but this presents hazards to the heart and any vessel that has weakened walls.

This decrease in radius is surprisingly small for this situation. To restore the blood flow in spite of this buildup would require an increase in the pressure difference of a factor of two, with subsequent strain on the heart.

ISCHEMIC PENUMBRA OF PARASYMPATHETIC DOMINANCE

In severe and/or chronic illness, profound changes occur in the hypothalamic-pituitary-thyroid axis. Ischemia and inflammation disrupt the porous Blood-Brain-Barrier surrounding the hypothalamus. The observed decrease in serum concentration of both hormones and neuroendocrine transmitter (neurotransmitters in the blood) are not compatible with a negative feedback loop.

Ischemia is a restriction in blood supply to tissues, causing a shortage of oxygen and glucose needed for cellular metabolism (to keep tissue alive, healthy and functioning properly). Ischemia is generally caused by problems with blood vessels, with resultant damage to or dysfunction of tissue or organs. It also means local anemia in a given part of a body sometimes resulting from congestion (such as vasoconstriction, red blood cell aggregation due to insulin resistance/diabetes). Ischemia comprises not only insufficiency of oxygen, but also reduced availability of nutrients and inadequate removal of metabolic wastes.

Hepatic Portal Hypertension

Parasympathetic Withdrawal (vasodilation) with blood pooling in the Abdominal Compartment makes the Movement Compartment and Brain/Spinal Cord Ischemic. At the periphery of the ischemic region, the so-called ischemic penumbra, neuronal damage throughout the body develops more slowly because blood flow arising from adjacent vascular territories (collateral flow) keeps blood perfusion above the threshold for immediate cell death. In the ischemic core, the major mechanism of cell death is energy failure caused by Oxygen/Glucose Deprivation (O2/GD). The hypothalamus and midbrain are most vulnerable to ischemia.

Neuron Vulnerability

Neurons in the most vulnerable areas cease to respond or show only faint responses and develop irreversible ischemic or post-ischemic damage. The hypothalamus responds to ischemic insults rigorously without having irreversible ischemic or post-ischemic damage.

The thalamus-hypothalamus interface represents a discrete boundary where neuronal vulnerability to ischemia is high in thalamus (like more rostral neocortex, striatum, hippocampus). In contrast hypothalamic neurons are comparatively resistant, generating weaker and recoverable anoxic depolarization similar to brainstem neurons, possibly the result of a Na/K pump that better functions during ischemia.

There is a well recognized but poorly understood caudal-to rostral increase in the brain`s vulnerability to neuronal injury caused by metabolic stress (insulin resistance).

Several brain regions, including the caudate, hippocampus, and hypothalamus, are vulnerable to hypoxic–ischemic brain injury. During O2/GD, hypothalamic neurons gradually depolarized during ischemic exposure. The O2/glucose deprivation (O2/GD) response induces failure of the Na+/K+ pump. The recovery is slow with chronic ischemic penumbrance

Without oxygen and glucose, neurons cannot generate the ATP needed to fuel the ionic pumps that maintain the ionic gradient across the neuronal membrane, mainly the Na+−K+ ATPase.

In the ischemic penumbra, the flow reduction is not sufficient to cause energy failure, and neurons remain viable for a prolonged period of time after the insult, but the neurons are stressed and critically vulnerable to pathogenic events that may tip their fragile metabolic balance. Excessive extracellular accumulation of glutamate is a major factor contributing to production of cytotoxic nitric oxide, free radicals and arachidonic acid metabolites. These events lead to necrosis or programmed cell death depending on the intensity of the insult and the metabolic state of the neurons. Injured and dying cells have a key role in post-ischemic inflammation because they release danger signals that activate the immune system.

Neurons that demonstrate particular vulnerability to ischemic challenges have been termed “selectively vulnerable neurons”. Of the entire forebrain, the neurons of the hippocampus are the most vulnerable.

Summary: Parasympathetic Dominance causes Ischemia to the Hippocampus, Hypothalamus, and Pituitary producing alterations in the HPA, HPT, HPD and HPG axis.

Melatonin Stimulates Parasites to Reproduce

Melatonin supports the synchronized reproduction of parasites. Parasites are attracted towards melatonin producing areas of the body during their reproductive cycles. Secretion of melatonin synchronizes the nocturnal release of microflilaria – the early larval stage of a parasitic nematode worm filarial. It follows that exogenous melatonin administration or the use of Blue Blocker Glasses during the day would also trigger release of microfilaria.

The nightly release of microfilaria into the circulation coincides with the feeding activity of parasites, a synchronization that is presumably an evolutionary adaptation favoring survival and transmission of the parasite.

88% of the cercariae (worm larvae) were shed between 11 a.m. and 3 p.m. and the average pattern is of circadian type, with the average peak at 1 p.m., and representing 27% of the total number of cercariae of the day. The rhythms of emergence are associated with nocturnal production of melatonin.

All worms were found in the distal 55% of the small intestine (ileum). During the night and morning, parasite was heavily concentrated in the jejunum and, during the day, worms are located more distally, with a heavy concentration in the ilium. Parasites have a migratory pattern that occurs with the initiation of gastric activity of the host. Worms move away from the areas producing digestive chemistry when production is initiated after eating. Two hours after feeding worms move towards the food. High fat diets result in a significant decline in worm dry weight, body area and uterine egg counts in worms. Low fat diets are conducive to increased parasite infestation.

Helminthic therapy, an experimental type of immunotherapy, is the treatment of autoimmune diseases and immune disorders by means of deliberate infestation with a helminth or with the ova of a helminth. Helminth therapy is being used as a treatment method for autoimmune and other inflammatory disorders.

There are a few studies highlighting the potential dangers of helminthic therapy. These are rare because as with Blue Blocker Glasses; no one wants to look at the dark side of Helminth therapy, hence few case studies.

Would you like to be advised of the negative potential of any therapy to consider before trying it.

Worms do not honor intestinal boundaries. They are capable of penetrating the intestinal lining. Especially, when overcrowding occurs from excess reproduction, e.g. melatonin stimulates parasite reproduction. This can also cause an obstruction by a large tangled mass of whipworms. Perforation of the ascending colon occurs as the worms expand their territory. How many people do you know that will go back to their social media friends to post something like this?

The good news is that the production and release of reactive oxygen species(ROS) stimulated by melatonin probably prevents most of the damage that normally occurs in parasitic infestation, e.g., eosinophil infiltration. This will also make the person with the parasitic overgrowth to be unable to feel any discomfort from the parasites.

Blue Blockers Stimulate the Chemical of Darkness

Melatonin is the ‘‘Chemical Signal of Darkness’’. Because the duration of melatonin production is the neurochemical signal for the annual change in night length,, wearing Blue Blocker Glasses increases the duration of the “biological night”.

Melatonin Is Linked to Antioxidants in Studies

If the only studies you read are linking melatonin to anti-oxidant and that is your only point-of-view. What could possibly go wrong with artificially increasing Melatonin through supplements or Blue Blocker Glasses. Melatonin like so many other hormones are “dose-dependent”. At “normal’ levels they do their normal duties. When they are too high or too low; the response is totally different and not in a good way.

Quick Summary of Melatonin Effects on the Body

  • Visible light decreases Melatonin levels.
  • Darkness increases Melatonin levels.
    • Blue Blocker Glasses increases Melatonin levels.
  • Melatonin is produced in multiple organs in the body.
  • Naturally occurring Melatonin increases Autoimmune cytokine storms and flairs during the Fall and Winter months.
    • Wearing Blue Blocker Glasses increases the amount of naturally produced Melatonin.
  • Melatonin lowers Thyroid Stimulating Hormone (TSH).
  • Melatonin Increases Polycystic Ovarian Syndrome (PCOS).
  • Melatonin increases the Th1, Th2 immune response response to antibodies.
  • Melatonin increases Th17 immune response
  • Melatonin increases parasite reproduction.

The amount of blue light in a natural environment varies depending on the time of the day (there is more in the morning) and on the reflecting surface such as snow, grass, water, sand or cement, blue blockers which are cutting all wavelengths below 540 nm are effective in naturalistic condition albeit that proper glasses frame are made to cover all angles. Blue light is also emitted by LEDs commonly found in computer screens meaning that many are exposed to it for long periods of time daily. This can cause in headaches and disruption to sleep routines. Felix Gray have developed glasses to filter blue light and block glare.

Blue Blocker Glasses cutting the blue portion of the light spectrum with orange lens glasses prevent the light-induced melatonin suppression, thereby increasing the production of melatonin. Blue Blocker Glasses represent an elegant means to increase melatonin production.

The immune system shares the same sensitivity to wavelengths as melatonin (as demonstrated by others using phase-shifting protocols,,,,, when these glasses are worn in the morning, greatly impede resynchronization of the biological clock by light.

There is a dose–response relationship between light intensity or irradiance and melatonin suppression.,,, Melatonin suppression is wavelength dependent with a peak sensitivity in the 446–477 nm (blue light) portion of the visible spectrum., Accordingly, it is possible to control the effect of light on the immune system by blocking the blue portion of the visible light.

A person’s prior light history has an impact on melatonin suppression or production., Those suffering from autoimmune disease are more likely to seclude themselves in dark rooms. Unknowingly, increasing their melatonin production and increasing their immune system reactivity.

The capacity of Blue Blocker Glasses to increase melatonin is sufficient to induce maximal melatonin suppression and about the same as encountered easily in the morning while driving.

Melatonin enhances the immune response.,, Melatonin supplementation or melatonin increasing Blue Blocker Glasses of both normal and immunocompromised individuals increases antibody responses and T helper cell activity., Melatonin administration appears to stimulate humoral immunity during early B cell development in the bone marrow. Melatonin has immune-enhancing effects and can exacerbate autoimmunity.

Melatonin Enhances the Immune Response

Melatonin has been shown to increase innate and acquired immunity, to activate the bone marrow and lymph nodes, to enhance NK cell activity and antibody-dependent cell cytotoxicity, to increase T cell proliferation and to activate monocytes and neutrophils.

Short, winter-like photoperiods enhance immune function relative to those exposed to long, summer-like days. The seasonal changes in immune function is due to changes in the melatonin levels.

The physiological properties of melatonin are not limited to its neuroendocrine role in controlling circadian rhythms; several other actions have been discovered. Melatonin has been shown to increase innate and acquired immunity, to activate the bone marrow and lymph nodes, to enhance NK cell activity and antibody-dependent cell cytotoxicity, to increase T cell proliferation and to activate monocytes and neutrophils. Melatonin can stimulate innate immune cells, primarily leukocytes, which represent an important anti-bacterial mechanism.

Th17 (harm) and Treg cells (protection) are both involved in the harm/protection balance of immune conditions such as autoimmunity or acute transplant rejection (miscarriage). The differentiation of Th17 using melatonin supplementation or melatonin inducing Blue Blocker Glasses aggravates autoimmune diseases and/or can induce serious complications in pregnancy.

Melatonin enhances the immune response. A large body of evidence supports the immunoenhancing role of melatonin. Exposure to short days (<12 h light/day) or daily melatonin supplements or melatonin increasing Blue Blocker Glasses may increase the size of the spleen. Melatonin enhances both cell-mediated and humoral immune function.

Melatonin supplementation or melatonin increasing Blue Blocker Glasses of both normal and immunocompromised individuals increases antibody responses and T helper cell activity. Melatonin administration appears to stimulate humoral immunity during early B cell development in the bone marrow.

Melatonin supplements and/or treatment for extended duration (e.g., Blue Blocker Glasses) induces physiological adaptations associated with winter, including reproductive regression and enhancement of certain aspects of immune function. In healthy individuals, melatonin has anti-inflammatory effects, while in those with Autoimmune conditions, melatonin is pro-inflammatory.

Melatonin Suppresses Thyroid Hormones

The hypothalamic-pituitary-thyroid axis (HPT axis) is a neuroendocrine system that regulates metabolism.  When the hypothalamus senses low circulating levels of the hormones T3 and T4, it signals to the pituitary, which then signals the thyroid gland to release T3 and T4.  T4 normally is converted to the more active T3, but T4 can also be converted to reverse T3 (rT3).  Reverse T3 works against the T3 receptor, so high levels can be detrimental.

Melatonin supplementation inhibits the TSH content in the pituitary. However, Melatonin supplementation blocks the stimulatory effect of TSH on thyroid cells responsible for the production and secretion of thyroid hormones thyroxine (T4) and triiodothyronine (T3).

During illness, profound changes may occur in the hypothalamic-pituitary-thyroid (HPT) axis. The most consistent change is a decrease in serum tri-iodothyronine (T3) level, but in severe illness, thyroxine (T4) may also decrease. The persistence of a normal or even decreased level of thyrotropin (TSH) in the face of decreased serum thyroid hormone concentrations implies a major change in HPT axis set-point regulation. Since these abnormalities of thyroid hormone concentration usually occur without any evidence of thyroid disease and disappear with recovery, they have been referred to as the `sick euthyroid syndrome’ or the `euthyroid sick syndrome’.

TSH serum levels are lower and those of free T4 are greater at night, when melatonin levels are higher, so that the response of pituitary to hypothalamic TRH and of thyroid to pituitary TSH is influenced by the pineal hormone melatonin, which alters the hypothalamic-pituitary-thyroid (HPT) axis function. Melatonin drives the molecular clockwork in the pituitary.

Melatonin & Thyroid Function

Melatonin has a suppressing action on thyroid function. Both hypothyroid and thyrotoxic patients have disturbed pineal function, which is not the case in those with weight issues. Those with hypothyroidism were found to have higher peak melatonin levels, total nighttime melatonin secretion, and urinary elimination of melatonin than normal individuals. Although thyrotoxic patients released a normal amount of melatonin during the night, their melatonin secretion peak occurs earlier in the night.

The molecular clockwork in the pituitary is strongly dependent on melatonin. Melatonin drives the rhythmic expression of clock genes in the pituitary, and the length of daytime light as well as melatonin supplements are involved in melatonin signaling.

Melatonin plays a role in the regulation of TSH release from the pituitary. Short days and long nights are correlated with decreasing levels of TSH in the pituitary. Moreover, chronic treatment with melatonin suppresses TSH release from the pituitary.

Melatonin has an inhibitory action on the Hypothalamic-pituitary-thyroid (HPT) axis. Long nights result in reduced levels of circulating thyroxin (T4). An active pineal gland produces melatonin, which inhibits thyrotrophin-releasing hormone (TRH) release from the hypothalamus. The effects of melatonin on the Hypothalamic-pituitary-thyroid (HPT) axis are similar to its effects on the Hypothalamic-pituitary-gonadal (HPG) axis.

Melatonin supplementation inhibits the TSH content in the pituitary. However, Melatonin supplementation blocks the stimulatory effect of TSH on thyroid cells responsible for the production and secretion of thyroid hormones thyroxine (T4) and triiodothyronine (T3). Free T3, T4 and TSH levels are lower with melatonin supplementation.

Melatonin is Not Just for Sleep Anymore

While most consider melatonin to be only produced by the pineal gland. It is produced throughout the body in much greater quantity (400x more in the gut). Melatonin is much more involved than previously thought. From enhancing autoimmune flairs during cytokine storms, to playing a role with infertility, melatonin and melatonin supplements used for ‘sleep problems’ enhances these conditions and not in a good way. It even plays a role in hot flashes and night chills.

If you have questions about sleep and you are having thyroid, autoimmune or infertility concerns with your health. Please contact my office.