Tuesday, November 11, 2008

Evoke Tranquility...

J. L. Merlin

Courtesy of Youtube.com

Melatonin has been on my mind...ever since Dr. D got me turned on to it here a little while ago. I know several people who take it and TOTALLY swear by it for insomnia. How can this hormone have such far-reaching benefits and effects?

It's used for:
--jet lag
--inducing hGH secretion
--breast cancer prevention
--oxidative damage protection
--vasculature un-responsiveness (relaxation/constriction with ACh or adrenaline)
--migraine prevention
--modulation of behavior and sleep patterns in autistic children
--natural aromatase inhibitor -- prevents excessive conversion of Testosterone to Estradiol (E2) and Androstenedione to Estrone (excessive Estrone (E1) is not good -- 'storage' form of estrogen in our adipose tissues and linked to promotion of cancer...and ??perhaps heart disease?)

Melatonin also is the master hormone behind skin changes in amphibians and reptiles.

How about us humans? You know how teenagers get all moody and starting staying up late and waking up late? And how they may transform from sweet kids to stinky Twilight sulkiness? Melatonin drops as sexual maturation occurs and this may lead to disrupted sleep cycles. This researcher and author of the textbook Dev Bio notes that Melatonin is the suspected hormone that allows human metamorphosis to occur: "The various morphological and behavioral changes of puberty are due to the actions of these hormones on the various target tissues. As in metamorphosis, there appears to be a maturation-inhibiting hormone whose activity decreases to permit the reactivation of development. In humans, this hormone is probably MELATONIN, whose serum concentration decreases as that of LH rises (Waldhauser and Dietzel, 1985)."

So who may experience dysregulation of Melatonin? Which came first...the chicken or the egg? Dysregulation of the hypothalamus/pituitary/pineal axis with wheat-assaults, in utero maternal vitamin D deficiency and/or neonatal/developmental EPA-DHA deficiency?

Are we epigenetically pushing our species into extinction?

The medical literature shows that many types of individuals are deficient in melatonin in the diurnal secretion that normally occurs at night -- in the pitch black inkiness of the night as nature intended (of course unless the full moon is shining). Normally melatonin starts to rise at 7pm and peaks at 2am then gradually falls again by dawn. Seasonal rhythms obviously exist also. Anciently controlled tides that we may not even be conscious of. In Scotland, scientists have recently shown how "Melatonin acts directly on anterior-pituitary cells, and these then relay the photoperiodic message back into the hypothalamus to control neuroendocrine output...(to trigger increases in TSH which subsequently signals activation of T3 (active thyroid hormone from T4) for increased metabolism and reproduction)...In mammals this provides the missing link between the pineal melatonin signal and thyroid-dependent seasonal biology (Hazlerigg Curr Biol. 2008 Aug 5;18(15):1147-52).

--Autistic spectrum children -- they tend to also display a genetic polymorphism, a deletion for the gene encoding the last enzyme for the making of Melatonin
--Individuals with coronary artery disease
--Type 2 diabetes with cardiac autonomic neuropathy (stiff heart rate variability (HRV))
--Wernicke-Korsakoff syndrome -- ie, brain-damage due to malnourishment -- seen in gastric bypass and alcoholics
--Sleep deprived individuals, swing shift workers, travel involving time zone shifts
--Hyperthyroid, hypothyroid (higher melatonin secretion but also higher elimination in the urine found)
--Environmental lighting conditions, drugs and other disease states: "Patients with alcoholism, migraine, postoperative pinealoma, panhypo-pituitarism, hereditary dystonia and schizophrenics on propranolol exhibited a decreased amplitude of their diurnal rhythm of melatonin." (Wetterberg L J Neural Transm Suppl. 1978;(13):289-310.)
--Fibromyalgia 31% less compared with healthy controls
--Alcohol consumption lowers Melatonin secretion 20% (HHHhhhmmmm...Patrone's+PEET*s apparently is a bad combo for my melatonin??? darn; don't worry -- light intake's fine)
--Obstructive sleep apnea

We are certainly learning a lot about the how all hormones are inter-related in the body. Like life, one disjointed connection can lead to impaired connections downstream. Are there ways to repair and strengthen the misconnected parts? I'm here at TYP...so I certainly believe in the plasticity of our bodies (and I aint referring to the wonders of silicon *wink*).

Thoughtful-mindfulness...meditation, prayer, yoga, tai-chi, massage, day-spa visits all achieve a level of control that is exerted on our 'third eye', the tiny pineal gland (see above; courtesy of here). I read a TIME magazine article ~2-3 yrs about how Buddhist monks were able to activate and light up parts of the brain on PET scans that normally are not associated with neural activity. They meditated (and according to the Dalai Lama teachings that I've read, this involves heightened awareness and enlightened empathy). Is this related to the Pineal Gland? Are there mechanisms that exist for synergizing our Pineal (found in the 3rd ventricle of the brain) with the rest of the brain, body and our deep unconsciousness? (like syncing an iPod to the computer?)

I dunno...but certainly other forms of meditation have been shown in small trials to result in significantly higher melatonin secretion from the Pineal Gland. Like a power nap an adequate night's slumber, how can plain old brain-power power up and protect our Pineal Gland? Apparently in very very very potent ways...! Maybe this justifies my addiction to day spas and yoga?

Tranquility is so super addictive.

Are we hard-wired for tranquility? Yes, I believe so once we are plugged into it.

Plaque-Busting Benefits of Yoga and Meditation
--"Experienced meditators practising either TM-Sidhi or another internationally well known form of yoga showed significantly higher plasma melatonin levels in the period immediately following meditation compared with the same period at the same time on a control night." (Sali A. Acute increases in night-time plasma melatonin levels following a period of meditation. Biol Psychol. 2000 May;53(1):69-78.)
--"Yogic practices for 3 months resulted in an improvement in cardiorespiratory performance (orthostatic tolerance, heart rate, BP, respiratory rate, dynamic lung function (such as forced vital capacity, forced expiratory volume in 1 second, forced expiratory volume percentage, peak expiratory flow rate, and maximum voluntary ventilation) and psychologic profile. The plasma melatonin also showed an increase after three months of yogic practices. The systolic BP, diastolic BP, mean arterial pressure, and orthostatic tolerance did not show any significant correlation with plasma melatonin. However, the maximum night time melatonin levels in yoga group showed a significant correlation (r = 0.71, p less than 0.05) with well-being score. Effects of Hatha yoga and Omkar meditation on cardiorespiratory performance, psychologic profile, and melatonin secretion. Sawhney RC J Altern Complement Med. 2004 Apr;10(2):261-8.)

Coronary/Vasculature Relationship and Role of Melatonin
Two publications from Northwestern med school recently reviewed the melatonin and the receptors that it binds and modulates: MT1, MT2, MT3. In one, the authors described the broad spectrum effects of Melatonin on a variety of organ systems (Masana MI Front Biosci. 2003 Sep 1;8:d1093-108. Molecular pharmacology, regulation and function of mammalian melatonin receptors). Like adrenaline (ie, NE/EPI) that binds beta- or alpha-receptors in various locations in our bodies, the end result can be inhibiting or stimulating activity; the physiological function depends on the location of the receptors as well. Likewise with Melatonin and the MT series, location and type of receptors determines function. Melatonin receptors affect every organ system: CNS (brain), hypothalamic-pituitary-pineal-thyroid-gonadal axis, cardiovascular, and immunity. The second article below describes inhibitory and activating effects of MT receptors.

Functional MT1 and MT2 melatonin receptors in mammals.
Dubocovich ML, Markowska M. Endocrine. 2005 Jul;27(2):101-10.

Melatonin, dubbed the hormone of darkness, is known to regulate a wide variety of physiological processes in mammals. This review describes well-defined functional responses mediated through activation of high-affinity MT1 and MT2 G protein-coupled receptors viewed as potential targets for drug discovery.

MT1 melatonin receptors modulate NEURONAL FIRING, ARTERIAL VASOCONSTRICTION, cell proliferation in cancer cells, and REPRODUCTIVE AND METABOLIC FUNCTIONS.

Activation of MT2 melatonin receptors phase shift circadian rhythms of neuronal firing in the suprachiasmatic nucleus, inhibit dopamine release in retina, INDUCE VASODILATION and inhibition of leukocyte rolling in arterial beds, and ENHANCE IMMUNE RESPONSES.

The melatonin-mediated responses elicited by activation of MT1 and MT2 native melatonin receptors are dependent on circadian time, duration and mode of exposure to endogenous or exogenous melatonin, and functional receptor sensitivity. Together, these studies underscore the importance of carefully linking each melatonin receptor type to specific functional responses in target tissues to facilitate the design and development of novel therapeutic agent. (OF COURSE! LET'S MAKE A PROFITABLE DRUG! ESP WHEN A CHEAP NATURAL ORIGINAL ALREADY EXISTS AND IS WIDELY AVAILABLE)
PMID: 16217123

And btw...STOP WHEAT
In polyglandular autoimmune thyroiditis (hypothyroidism), melatonin levels were naturally found to be low particularly when more fatigue was observed by the study participants. The more fatigue, additionally, the more auto-antibodies were found associated with more organs. The adrenals were attacked in addition to the ovaries, thyroid and/or TPO (thyroid peroxidase). It is not clear precisely the relationship between thyroid function, melatonin and auto-antibodies here... In trials looking at simple hypothyroidism, often melatonin levels are fine or mildly shifted. In the case where multiple glands/organs are affected, the melatonin effects appear more significant. I never realized we could make auto-antibodies to our adrenals. But the medical literature is chock full of stories of auto-antibodies produced against nearly ANYTHING in our bodies -- including our p450 enzymes and even...(!!) mitochondria (our little nuclear ATP powerhouses).

??Can we possibly produce auto-antibodies to our pineal? Or calcify it to rock or pebble? Why not? I believe we could...

Wheat as you aware is not only a common food allergen, but it increases gene expression (62 in this trial detected) of a variety of stress hormones, cytokine-chemokine–mediated immunity, and the interleukin pathway, and MMPs (metalloproteinases) (prior post on the FUNGENUT study). Does wheat trigger the increased production of auto-antibodies? Absolutely. Hypothyroidism is a common autoimmune manifestation of silent celiac disease, in other words wheat intolerance. Other organs or tissues frequently 'burnt to a toast' include: Fingers/Rheumatoid; Wrists/CTS; Knees/osteoarthritis; Gallbladder/biliary dz; Insulin receptors/Type 2 Diabetes; Pancreas/Type 1 Diabetes; Ovaries/infertility; Spit glands/Sjogrens; Myelin/MS; et cetera. How about Muscles/fibromyalgia? The Brain?? Consideration of complete wheat cessation is necessary I believe to prevent burning out multiple organs (including the coronary vasculature).

[The fatigue syndrome in autoimmune thyroiditis with polyglandular activation of autoimmunity][Article in Czech]
Zamrazil V et al.Vnitr Lek. 1998 Aug;44(8):456-60.

The authors compared in a group of 118 patients with autoimmune thyroiditis and a positive antibody titre against ovaries the grade of fatigue with the presence of organ specific and non-specific autoantibodies in the peripheral blood stream, antibodies against EBV and CMV, immunoglobulin concentrations, biochemical parameters of the lipid metabolism, glucose tolerance, ion balance and melatonin and serotonin levels. Patients with autoimmune thyroiditis were differentiated according to the degree of fatigue into three groups: 38 with fatigue typical for CFS (chronic fatigue syndrome), 30 with occasional fatigue and 50 without the feeling of fatigue. Fatigue of the CSF type was characterized by a significantly higher incidence of autoantibodies against the adrenals and a higher cholesterol level. Increased fatigue of the patients was associated with a lower melatonin level, a higher serotonin level and a lower M/S ratio as compared with patients without fatigue. In other indicators no differences were found. Fatigue in CFS could be associated, similarly as in autoimmune endocrinopathies, with impaired immunoendocrine regulation. In autoimmune thyroiditis, regardless of the concomitant presence of fatigue, in addition to antibodies against thyroid peroxidase most frequently antibodies against the ovaries were detected.
PMID: 10358448


kelly said...

I love your blog. Thanks for the information on Melatonin. I just started taking 5mg sublingual and I think it might be helping me sleep. Do you think it is safe to take every night? Keep up the great information.

Dr. B G said...

Hey Kelly!

Welcome! I believe the longest human trials are only a few months for melatonin so of course chronic daily use has not been 'evaluated.'

It sounds like you notice positive effects. Obviously normalizing function and peak melatonin secretion is good goal. I myself have tried it 1-2 times and noticed relief as well. Conversely, if you take vitamin D ('the sunshine hormone'), make sure you don't take in the evening because I've noticed it can cause insomnia for some (including me).


Anonymous said...

Have you read the book "Lights out"?

Dr. B G said...

I haven't had a chance -- though people have brought it up half-a-dozen times to me in the last 3 mos! I should esp if there are discussions on hormones. Thank you!


Anonymous said...

The great thing about your blog is that you never really know what is going to turn up next; but you do know that sooner rather than later a topic will jump oiut form the page and grab your attention.

As I have taken a greater interest in health and diet two things have struck me:

(i) The human body is a beautifully complex machine.

(ii) The medical profession in general is prone to claiming a greater degree of understanding of how the human body actually functions than is justified by the current knowledge base.

Drugs are a very poor second best to a correctly funtioning healthy body. All have significant side effects which are poorly understood in many cases, or swept under the carpet. In most cases they target a symptom rather than the underlying cause. For example, a patient may have lower blood pressure because they go to the men's room (or lady's) more frequently, but they are suffering from the same underlying metabolic abnormalities. Indeed by taking the medication (BP meds, statins (most likely)) and folllowing the orthodox low fat high carb diet that may actually be accelerating the decline in their own health.

I believe doctor's should view drugs very much as a last resort, for use when all other options have been exhuasted and where the benefits, as measured in quality of life and greater life expectancy, very clearly exceed the side effects (worse quality of life).

Nearly all hormone in the human body perform more than one function, eg, insulin, vitamin D (a sort of hormone). Treating diabetes with a powerful hormone like insulin purely from the perspective of controlling blood glucose, without takoing on board all of the other functions of insulin - eg, fat storage and release, muscle growth, etc, its impact on blood pressure and atherosclerosis, cholesterol production, etc, is asking for trouble.

Medicine would be well served if most practitioners accepted their limitations and focused more on rprevention and less on drug therapy. Of course one major problem here is the fixation with fat avoidance and the grain absed food pyramid - adherence to which very likely hastens the arrival of the very conditions it is intended to prevent.

With our current knowledge base I believe the best approach in to eat whole foods, vegetables, drink water, avoid sugars and man made fats, and keep active. Prevention is much more effective, and less expensive, than intervention. Oh, and get plenty of good quality sleep, laugh and get some sunligh whenever the opportunity presents itself.


Dr. B G said...


I couldn't have said it better than as you stated!!

So true we have so much power in our own hands to prevent and improve our health.

If only it were more mainstream...*impatient sigh* Slowly though everday I see the tide changing! First our families, then the village, then the WORLD.


Anonymous said...

Wenicke-Korsakoff syndrome is a disease which is caused by alcoholism. Which is why medical science proves once again that alcohol can cause harm to our body.