circadianism

[Guest guest]

sorry: forgot to copy the group...

> Good question. That's why I asked it back in April.

haven't looked back that far

> If I have to work on a night shift, for example from midnight to 8a.m., > at what time should I take my LDN? > > Continue to take LDN as recommended above; i.e., between 9pm and > 3am. This relates to the fact that the endorphins for each day are > always produced in the pre-dawn hours, regardless of the hours when> one is awake or sleeping

Not always, and not regardless. Note individual and series variations, variations due to pathology, and habitualvariations (see mice and rats).

J Clin Invest, December 2001, Volume 108, Number 11, 1563-1566 Perspective Series Introduction: The immuno-neuroendocrine interface Shlomo Melmed Cedars-Sinai Research Institute, University of California Los Angeles,School of Medicine, Los Angeles, California 90048, USA. Phone: (310) 423-4691; Fax: (310) 423-0119; E-mail: melmed@...<mailto:melmed@...>.

"Essential cellular functions maintaining metabolic and endocrine control require a homeostatic, nonstressed pattern of ACTH and glucocorticoid secretion, which can readily respond to counteract life-threatening insults. ACTH secretion is characterized by both circadian periodicity and ultradian pulsatility (Figure 2) generated by CRH release and also influenced by peripheral corticosteroids. ACTH secretion peaks before 7 am and nadir adrenal steroid secretion occurs between 11 pm and 3 am, with periodic secretory bursts occurring throughout the day. These rhythms are entrained by visual cues and the light-dark cycle, and stress results in increased ACTH pulse amplitude (8). Adrenal ACTH receptors signal via adenyl cyclase to regulate adrenal gland size, structure, and function. p450 enzyme transcription, cortisol, aldosterone, 17-OH progesterone, and, to a minimal extent, adrenal androgens are induced by ACTH. The neuroendocrineand immune systems also communicate bidirectionally, and stress-induced glucocorticoids, catecholamines, and CRH mediate peripheral immune responses (9)."

J. Clin. Endocrinol. Metab. 68: 1019-1026

Association between circadian rhythms of endogenous hypothalamic opioidpeptides and of natural killer cell activity.

Mozzanica N, Finzi AF, Foppa S, Vignati G, Villa ML.

2nd Department of Dermatology, University of Milano, Italy.

To explore in man the hypothesis that natural killer cell activity and hypothalamic-hypophyseal hormones constitute a mutually coupled multioscillator system, we analysed and compared, in 11 healthy volunteers, the circadian variations in plasma concentrations of beta-endorphin, met-enkephalin and alpha-MSH, and of natural killer activity of peripheral blood lymphocytes. Natural killer cell activity and plasma beta-endorphin levels showed a similar circadian rhythm with the peak in the morning (acrophases at 06.14 and 08.25, respectively), whereas the circadian rhythm of met-enkephalin was approximately in antiphase to the natural killer rhythm (acrophase close to 17,00 hours). Although daily variation of alpha-MSH showed greater inter-individual variability, a circadian rhythm was statistically validated. Analysis of correlation between rhythmometric parameters (mesor, amplitude, peak and nadir) of natural killer cell activity vs neuro-endocrine hormones revealed that the minimum and medium daily concentrations of beta-endorphin correlated directly with the corresponding parameters of natural killer activity, while the maximum and medium concentrations of met-enkephalin were inversely correlated with the peak and the mesor of natural killer activity. The amplitude of natural killer cell activity oscillations correlated directly with the peak, mesor and nadir concentrations of alpha-MSH. We show here that circadian rhythms of some neuroendocrine hormones of the hypothalamic-hypophyseal axis, i.e. beta-endorphin, met-enkephalin and alpha-MSH, are significantly coupled to daily oscillations of NK cell activity

Int J Neurosci. 1992 Apr;63(3-4):299-305.

Interleukin-1 beta and beta-endorphin circadian rhythms are inversely related in normal and stress-altered sleep.Covelli V, Massari F, Fallacara C, Munno I, Jirillo E, Savastano S, Tommaselli AP, Lombardi G. 2nd Medical School, Universityof Naples, Italy.

Normal sleep is associated to physiological nocturnal rises in Interleukin 1 beta (IL 1 beta) secretion. The 24 h pattern of IL 1 beta, beta-Endorphin (beta-EPH), ACTH and cortisol (F) production was evaluated in four male healthy volunteers. Two subjects were unable to sleep, due to the stress of the experiment; in these cases, no detectable plasma IL 1 beta secretion, both diurnal and nocturnal, was present, beta-EPH plasma levels were significantly higher (p < 0.01) than in the subjects who slept regularly and, in one case, increased F plasma levels were also reported. A strong negative correlation between IL 1 beta and beta-EPH plasma levels was present in all the cases. In conclusion, stress-induced sleep alterations might deeply affect both diurnal and nocturnal IL 1 beta plasma secretion, probably due to the hypothalamus-pituitary-adrenal axis (HPAA) activation, and beta-EPH might be the reliable marker of the stress-induced HPAA activation level. Chronobiol Int. 1990;7(2):135-42. Diurnal variations of beta-endorphin at rest and after moderate intensity exercise.

McMurray RG, Hill D, Field KM. Department of Physical Education, University of North Carolina, Chapel Hill 27599-8700.

To determine the effect of time of day on circulating beta-endorphin concentrations 14 men exercised at 75% of their maximal capacity at 0600, 1200, 1800 and 2400 hr. Each trial was separated by 3-5 days and preceded by a normal sleep cycle except for the 0600 hr trials which was preceded by 6 hr sleep. Resting physiological data indicated normal diurnal variations in heart rate, core temperature and oxygen uptake, being lowest during the 0600 hr trials and highest during the 1800 hr trials. Resting plasma beta-endorphin concentrations averaged 11.9 +/- 8.4 pmol/l during the 0600 hr trials, significantly greater than the 2400 hr trials (6.4 +/- 3.6 pmol/l; P less than 0.05). No other significant differences existed at rest. Post exercise beta-endorphin concentrations were elevated and found to be inversely related to time of day with the 0600 hr trials having the highest mean (25.7 +/- 14.7) and the 2400 hr trials the lowest (14.7 +/- 8.3). These data suggest that the plasma beta-endorphin concentrations at rest and after exercise are affected by the time of day. The results also suggest that the changes in beta-endorphin associated with exercise are not major contributors to cardiorespiratory control or changes in psychological effect associated with exercise.

J Clin Endocrinol Metab. 1989 Jun;68(6):1019-26. Circadian, ultradian, and episodic release of beta-endorphin in men, and its temporal coupling with cortisol. Iranmanesh A, Lizarralde G, ML, Veldhuis JD. Endocrine Section, Veterans Administration Medical Center, Salem, Virginia 24153.

beta-Endorphin and ACTH derive from a common peptide precursor. Although much is known about the physiological patterns of ACTH release, neither the minute to minute regulation of beta-endorphin secretion nor its temporal relationship to cortisol has been characterized. As an initial step to defining the regulation of beta-endorphin release in man, we studied the circadian periodicity, ultradian rhythmicity, and episodic pulsatility of serum beta-endorphin concentrations in seven normal men. Blood sampling was conducted at 10-min intervals for 24 h, and the subsequent serum samples were assayed by a two-site immunoradiometric assay. Computerized analysis of the subsequent beta-endorphin time series revealed a mean beta-endorphin pulse frequency of 13 +/- 1 (+/- SE) peaks/24 h, corresponding to an interpulse interval of 100 +/- 7 min. The mean maximal peak height of beta-endorphin pulses was 31 +/- 3 pg/mL (9.0 +/- 0.8 pmol/L), which represented an incremental increase of 11 +/- 1 pg/mL 3.2 +/- 0.4 pmol/L; 63 +/- 13%) above the preceding nadir. The average beta-endorphin peak exhibited a duration of 68 +/- 6 min. Fourier analysis revealed a significant circadian amplitude of 6 +/- 1 pg/mL (1.6 +/- 0.4 pmol/L; 23% of the 24-h mean concentration), with an acrophase (time of maximum value) at 1043 h (+/- 40 min). Spectral analysis also disclosed beta-endorphin rhythms with mean periodicities of 29 +/- 4, 42 +/- 4, and 61 +/- 5 min. Gel filtration chromatography confirmed that serum beta-endorphin peaks contained significantly more immunoactive beta-endorphin [62 pg/mL (18 pmol/L)] than did the flanking nadirs [16 and 18 pg/mL (4.6 and 5.2 pmol/L)]. Auto- and cross-correlation analyses of serum beta-endorphin and cortisol concentrations followed by autoregressive modeling disclosed that all seven men had significant positive cross-correlations between serum beta-endorphin and cortisol considered simultaneously or when cortisol lagged beta-endorphin by 10 min. A negative cross-correlation was found in five of the seven men when cortisol was considered to lead beta-endorphin by 20 or 30 minutes. We conclude that beta-endorphin is released physiologically in a pulsatile manner with circadian and ultradian rhythmicity and a close temporal coupling to cortisol.

Dev Pharmacol Ther. 1989;12(1):1-6.

Diurnal rhythm of beta-endorphin in neonates. Sankaran K, Hindmarsh W, Tan L. Department of Pediatrics, University of Saskatchewan, Saskatoon, Canada.

In an attempt to prove whether beta-endorphin diurnal rhythm existed in neonates, 17 infants with a mean (+/- SD) gestational age of 31.7 +/- 4.8 weeks and a birth weight of 1,790 +/- 898 g were studied at a mean postnatal age of 3.3 +/- 0.5 days. Plasma samples were obtained from a pre-existing umbilical arterial line at 09.00 h, noon and 15.00 h. Mean plasma concentrations of beta-endorphin were 68.3 +/- 27.7, 54.5 +/- 13.7, and 45.1 +/- 10.8 pg/ml, respectively. Highly significant (p = 0.0002) variation of plasma beta-endorphin concentration was observed in these neonates suggesting the presence of a diurnal rhythm of beta-endorphin in neonates. It is important to specify the time of collection of blood samples for determination of opiates in neonates.

Endocrinol Jpn. 1986 Oct;33(5):713-9.

Diurnal rhythms of proopiomelanocortin-derived N-terminal peptide, beta-lipotropin, beta-endorphin and adrenocorticotropin in normal subjects and in patients with 's disease and Cushing's disease.

Sekiya K, Nawata H, Kato K, Motomatsu T, Ibayashi H.

In order to clarify the diurnal pattern of secretion of plasma immunoreactive (IR) proopiomelanocortin (POMC)-derived peptides, IR-N-terminal peptide (Nt), IR-beta-endorphin (Ep), IR-beta-lipotropin (LPH), and IR-ACTH (ACTH) in normal subjects and in patients with 's disease and Cushing's disease, we measured these 4 peptides in the same plasma obtained at 0900 h and then every three hours until 0600 h at the next day. All four peptides showed diurnal rhythms with the peaks at 0600 h, and the nadirs of ACTH, LPH, Ep and Nt were at 0000 h, 0000 h, 1800 h and 0300, respectively in normal subjects. In patients with 's disease, these four peptides also showed diurnal rhythms with the peaks at 0600 h for ACTH and Ep and at 0900 h for LPH and Nt, and the nadirs at 2100 h for ACTH and Ep and at 0000 h for LPH and Nt. The molar ratios of Ep/ACTH, LPH/ACTH and Nt/ACTH in plasma also presented diurnal variations in normal subjects and in patients with 's disease. On the other hand, in patients with Cushing's disease, ACTH, LPH and Nt showed no rhythmicity or change in molar ratios of Ep/ACTH, LPH/ACTH or Nt/ACTH. Only Ep showed diurnal variation. The molar ratios of Ep/ACTH, LPH/ACTH and Nt/ACTH in patients with Cushing's disease were significantly higher than those in normal subjects and in patients with 's disease at 0000 h.

Life Sci. 1986 Jun 16;38(24):2263-7.

Diurnal beta-endorphin changes in human cerebrospinal fluid.

Barreca T, Siani C, Franceschini R, Francaviglia N, Messina V, Perria C, Rolandi E.

Plasma and cerebrospinal fluid (CSF) beta-endorphin levels were determined by a RIA method in seven hydrocephalic male patients. The samples were simultaneously collected every two hours from 8 AM to 12 midnight and every hour from 1 AM to 7 AM. In both plasma and CSF beta-endorphin levels showed significant time-related variations during the 24 hour period. These results suggest the existence of diurnal CSF beta-endorphin variations analogous to those observed in plasma.

Psychopharmacology (Berl). 1986;88(4):496-9.

Diurnal rhythm of plasma beta endorphin, cortisol and growth hormone in schizophrenics as compared to control subjects. Gil-Ad I, Dickerman Z, Amdursky S, Laron Z.

The diurnal variation of plasma beta endorphin was studied in ten schizophrenics, and in age/sex matched control subjects. In the controls beta endorphin was high in the morning (21.0 +/- 3.5 pmol/l) and decreased towards evening. In the schizophrenic group the beta endorphin fluctuated randomly, ranging within 9-40 pmol/l throughout the day. Plasma cortisol showed a normal diurnal pattern in both groups. The mean plasma cortisol levels in the schizophrenics were significantly higher than in the controls throughout the day. The pattern of plasma human growth hormone (hGH) level was similar in both groups at the time tested. It is hypothesized that the instability of beta endorphin secretion may contribute to the pathogenesis of schizophrenia.

A study of 24-hour profiles of plasma met-enkephalin in man.

Shanks MF, Clement- V, Linsell CJ, Mullen PE, Rees LH, Besser GM.

Met-enkephalin has recently been demonstrated to circulate in human plasma and using this highly specific extracted radioimmunoassay the fluctuations of plasma Met-enkephalin in man were studied over 24 h. The subjects were 6 healthy volunteers. Following a 24 h adaptation period in the metabolic ward and sleep laboratory, an i.v. catheter was inserted. Blood samples were taken at hourly intervals through the day and at 30 min intervals between 23.00 h and 07.00 h. Sleep was monitored polygraphically. There was no regular rhythm discernible in plasma Met-enkephalin levels throughout the 24 h, nor was there any relationship with sleep or food intake. In a further 3 subjects beta-LPH and beta-endorphin levels as estimated by N- and C-terminal beta-LPH radioimmunoassay were elevated on waking compared with 01.00 h, suggesting a nyctohemeral rhythm. In contrast to the correlated circadian fluctuations in beta-LPH, ACTH and beta-endorphin levels therefore, the lack of circadian rhythmicity and dissociation of plasma Met-enkephalin from plasma levels of the former group of peptides suggests control mechanisms for the secretion of Met-enkephalin are quite different and adds support to the concept of separate Met-enkephalin precursors. Diurnal rhythm of plasma immunoreactive beta-endorphin and its relationship to sleep stages and plasma rhythms of cortisol and prolactin.

Dent RR, Guilleminault C, Albert LH, Posner BI, BM, Goldstein A.

To determine the diurnal rhythm of plasma beta-endorphin (beta-End), 10 healthy male volunteers between the ages of 20 and 32 yr were studied in a sleep laboratory setting for a 24-h period. Blood samples were taken through an indwelling catheter at 0800, 1000, 1400, 1800, 2200, 2300, and 2400 h and then half-hourly until 0730 h, and they were then assayed for total beta-End-like immunoreactivity (ir beta-End), PRL, and cortisol. Subjects were habituated by spending the night before the study in the sleep laboratory with an indwelling catheter and electrodes for sleep recording in place. There was a clear diurnal variation of ir beta-End, with lowest levels between 2200 and 0330 h and highest levels between 0400 and 1000 h. There was no evidence for direct entrainment with sleep stage. There was a close correlation with cortisol levels, suggesting a similar secretory pattern for beta-End and PRL in only 5 of the subjects. Because the beta-End antiserum used has a cross-reactivity of 30% with beta-lipotropin gel permeation chromatography was done on extracts of plasma taken at 1400, 2400, 0400, and 0730 h for each subject. The peak in the beta-End elution position showed a clear diurnal variation similar to that of ir beta-End.

> Waking up with problems is usually > the case. When you walk too much, you feel it after > sleeping. When you bang yourself, even if you're in pain, > when you wake up after some sleep, you really feel it. > After a car accident, you think you're fine, but the next > day you wake up sore all over. Not sure that has to do > with sun-cycle related factors, but when you sleep, the body > checks out what's going on and sends in the repair crews, > hence the problem when waking up that wasn't there before > going to sleep.

I never had a warning. I was fine the night before. Might have been stress effects. Sore all over is what endorphin is there to fix. Stress related (accident, injury, etc.) release of endorphin is not circadian. And other hormones are released at different times, as well as are NK cells.

Maybe the stress troops just couldn't keep up with the injury. But I do feel better with MS, in the morning. So that's when I do my exercise. And all my exacerbations have been at night. Maybe my circadian was low and my stress endorphins couldn't get up high enough as well. Circadian endorphins are low, absent, or delayed in many sick people.

Seems to be some disagreement about the exact time. It seems to be a cosinusoid

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The nadir is the low point and the acrophase is the peak or high point. The nadir seems to be somewhere between 6pm and 11pm (some said 3AM), with the peak about 12 hours later, between 6am and 8:30am (some said 4-11am). Lets say 7am for the peak and 7pm for the trough. Some also found half-hourly, hourly and other frequencies, but these are the main ones. One of the studies was very specific about 10:43 but that may be too many digits of accuracy and it is a fourier series average. Anyway it sounds like whenyou get up and when you go to bed. Just when you need endorphins. Anybody noticed that they are worse as the day(and evening) wears on?

It is trainable by light over time which accounts for nocturnal versions. In particular rats and mice are the opposite of us.

Babies are born with it, probably because the mother'sblood trains them.

It should be studied what the levels do during entrainment.Maybe they get low and if you have insomnia they tank.

I also didn't find any studies on variations in MS patients.

Are we asleep yet?

-Sullivan