LakeMountD
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One of the biggest questions I have gotten over the years asks the best time to take supplements, specifically those whose bioavailability and efficacy are dependent on the liver. These supplements usually include supplements such PH's and other muscle builders. These compounds are methylated and slow the degradation process in the liver, increasing their plasma half life. This puts stress on the liver as enzymes are rapidly produced to try and combat the foreign substance. One of the biggest pieces of advice I have seen people give is to not take any liver support supplements during or before a cycle so that liver enzyme levels are lower and the effect of the compound is greater.
There is a better way, however. Instead of using another supplement to lower or raise liver enzymes, here is some information that will show you that chronotherapy is an exciting new field emerging in the medical arena that I have done research on while in pharmacy school. Chronotherapy is the study of how substances interact with the body at various stages of the day. A patient taking doxazosin may experience different effects whether they take it during the day or at night. So how does this apply to taking muscle building supplements?
Research has shown that hypogonadal men, or men whose hormone levels are low produce more melatonin. Hypergonadal men, the complete opposite, produce much less. This is apparent to anyone who has taken a steroidal product before since you might notice it often times because harder to sleep. Night awakenings are also experienced more. All in all the gonadal hormones regulate pineal gland secretion, which is where melatonin is secreted. I found a good article stating just this:
Abnormal melatonin secretion in hypogonadal men: the effect of testosterone treatment
Rafael Luboshitzky , Oded Wagner , Shachar Lavi , Paula Herer & Peretz Lavie
1 Endocrine Institute, Haemek Medical Center, Afula, 2 Sleep Research Centre, Haifa and Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel
Correspondence to: Dr Rafael Luboshitzky
ABSTRACT
OBJECTIVE
We have recently demonstrated that GnRH deficient male patients have increased nocturnal melatonin secretion, whereas hypergonadotrophic hypogonadal males have decreased melatonin levels. We were interested in determining whether testosterone (T) treatment (when T levels were well matched with pubertal control values) has an effect on melatonin secretory profiles in these patients.
DESIGN
Prospective, controlled.
SUBJECTS
Six male patients with idiopathic hypogonadotrophic hypogonadism (IGD), six males with hypergonadotrophic hypogonadism due to Klinefelter's syndrome (KS) and seven controls. Patients were examined before and during the administration of 250 mg testosterone enanthate/month for four months.
MEASUREMENTS
Serum samples for melatonin levels were obtained every 15 minutes from 1900 to 0700 h in a controlled light-dark environment. The results of FSH, LH, T and oestradiol (E2) (determined at hourly intervals) and melatonin profiles, were compared with the pre-treatment values in each group, and with values obtained in the control group.
RESULTS
All 12 patients had low pre-treatment T levels (1.4 ± 0.7 in IGD and 2.0 ± 0.4 in KS vs. 19.8 ± 2.3 nmol/l in controls) and attained normal levels after four months of T treatment (19.5 ± 7 in IGD and 22.7 ± 3.8 nmol/l in KS). Serum LH, FSH and E2 levels (11 ± 4 IU/l, 24 ± 10 IU/l and 113 ± 12 pmol/l, respectively) were still elevated in KS during T treatment as compared with values in controls (2 ± 1 IU/l, 2 ± 1 IU/l and 67 ± 4 pmol/l, respectively). In IGD, serum LH (0.12 ± 0.1 IU/l) and FSH (0.16 ± 0.2 IU/l) levels during T treatment were suppressed. Pretreatment melatonin levels in IGD were greater than those in age-matched pubertal controls while in KS, melatonin levels were lower than values in controls. Melatonin levels were equal in all 12 hypogonadal patients and controls when T levels were well matched. Mean (±SD) dark-time melatonin levels decreased from 286 ± 18 to 157 ± 26 pmol/l in IGD and increased from 92 ± 19 to 183 ± 48 pmol/l in KS (vs 178 ± 59 pmol/l in controls). The integrated melatonin values decreased in IGD (from 184 ± 14 to 102 ± 21 pmol/min. l × 103) and increased in KS (from 64 ± 13 to 123 ± 40, vs. 116 ± 39 pmol/min. l × 103 in controls). No correlations were found between melatonin and LH, FSH or E2 levels.
CONCLUSIONS
These data indicate that male patients with GnRH deficiency have increased nocturnal melatonin secretion while in hypergonadotrophic hypogonadal males melatonin secretion is decreased. Testosterone treatment normalized melatonin concentrations in these patients. Taken together, the results suggest that GnRH, gonadotrophins and gonadal steroids modulate pineal melatonin in humans.
Now you are probably thinking that this still doesn't make much sense. It will in a moment. Melatonin has been shown to be a very potent anti-aging and antioxidant peptide-hormone. One of the main pathways for this ability is through liver enzyme production, especially glutathione levels. Within 90 minutes of melatonin production there was a marked increase of over 100% of glutathione activity. This can be seen here:
Melatonin stimulates the activity of the detoxifying enzyme glutathione peroxidase in several tissues of chicks
Marta I. Pablos, 1 Maria T. Agapito, 1 Regina Gutierrez, 1 Jose M. Recio, 1 Russel J. Reiter, 2 Lornell Barlow-Walden, 2 Dario Acuña-Castroviejo, 3 Armando Menendez-Pelaez 4
1 Department of Biochemistry, Molecular Biology and Physiology, Facultad de Ciencias, Universidad de Valladolid, Valladolid, Spain 2 Department of Cellular and Structural Biology, The Health Science Center at San Antonio, San Antonio, TX USA 3 Department of Physiology, Facultad de Medicina, University of Granada, Granada, Spain 4 Department of Morphology and Cellular Biology, University of Oviedo, Oviedo, Spain
ABSTRACT
Abstract: The pineal hormone melatonin has been shown to directly scavenge free radicals and to stimulate, in the mammalian brain, at least one enzyme, glutathione peroxidase, which reduces free radical generation. In the present studies, we examined the effect of melatonin on glutathione peroxidase activity in several tissues of an avian species. Melatonin (500 μg/kg), when injected into chicks, increased glutathione peroxidase activity within 90 min in every tissue examined. Tissue melatonin levels, measured by radioimmunoassay, also increased following its peripheral administration. Depending on the tissue, the measured increases in melatonin varied from 75% to 1,300% over the control values. The melatonin-induced increases in glutathione peroxidase activity varied with the tissue and were between 22% and 134%. These percentage increases in glutathione peroxidase activity were directly correlated with tissue melatonin content. These results suggest that melatonin induces the activity of the detoxifying enzyme, glutathione peroxidase, in several tissues in the chick. The findings also suggest that melatonin would reduce the generation of highly toxic hydroxyl radicals by metabolizing its precursor, hydrogen peroxide. Because of this ability to stimulate glutathione peroxidase activity, melatonin should be considered as a component of the antioxidative defense system in this avian species.
With this being said it would be better to keep your dosages to the morning and afternoon. It has been argued before that, "I don't take melatonin" and "but testosterone levels are highest in the morning". Melatonin is produced naturally and is responsible for your circadian rhythms (biological clock), supplementation will further increase levels of glutathione and other liver enzymes and a lot of people who supplement with anabolics use melatonin. To the second statement while taking anabolics natural hormones are often extremely low so taking them at any point during the day will make it the dominant hormone. Depending on when you go to sleep this could change.
There is a better way, however. Instead of using another supplement to lower or raise liver enzymes, here is some information that will show you that chronotherapy is an exciting new field emerging in the medical arena that I have done research on while in pharmacy school. Chronotherapy is the study of how substances interact with the body at various stages of the day. A patient taking doxazosin may experience different effects whether they take it during the day or at night. So how does this apply to taking muscle building supplements?
Research has shown that hypogonadal men, or men whose hormone levels are low produce more melatonin. Hypergonadal men, the complete opposite, produce much less. This is apparent to anyone who has taken a steroidal product before since you might notice it often times because harder to sleep. Night awakenings are also experienced more. All in all the gonadal hormones regulate pineal gland secretion, which is where melatonin is secreted. I found a good article stating just this:
Abnormal melatonin secretion in hypogonadal men: the effect of testosterone treatment
Rafael Luboshitzky , Oded Wagner , Shachar Lavi , Paula Herer & Peretz Lavie
1 Endocrine Institute, Haemek Medical Center, Afula, 2 Sleep Research Centre, Haifa and Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel
Correspondence to: Dr Rafael Luboshitzky
ABSTRACT
OBJECTIVE
We have recently demonstrated that GnRH deficient male patients have increased nocturnal melatonin secretion, whereas hypergonadotrophic hypogonadal males have decreased melatonin levels. We were interested in determining whether testosterone (T) treatment (when T levels were well matched with pubertal control values) has an effect on melatonin secretory profiles in these patients.
DESIGN
Prospective, controlled.
SUBJECTS
Six male patients with idiopathic hypogonadotrophic hypogonadism (IGD), six males with hypergonadotrophic hypogonadism due to Klinefelter's syndrome (KS) and seven controls. Patients were examined before and during the administration of 250 mg testosterone enanthate/month for four months.
MEASUREMENTS
Serum samples for melatonin levels were obtained every 15 minutes from 1900 to 0700 h in a controlled light-dark environment. The results of FSH, LH, T and oestradiol (E2) (determined at hourly intervals) and melatonin profiles, were compared with the pre-treatment values in each group, and with values obtained in the control group.
RESULTS
All 12 patients had low pre-treatment T levels (1.4 ± 0.7 in IGD and 2.0 ± 0.4 in KS vs. 19.8 ± 2.3 nmol/l in controls) and attained normal levels after four months of T treatment (19.5 ± 7 in IGD and 22.7 ± 3.8 nmol/l in KS). Serum LH, FSH and E2 levels (11 ± 4 IU/l, 24 ± 10 IU/l and 113 ± 12 pmol/l, respectively) were still elevated in KS during T treatment as compared with values in controls (2 ± 1 IU/l, 2 ± 1 IU/l and 67 ± 4 pmol/l, respectively). In IGD, serum LH (0.12 ± 0.1 IU/l) and FSH (0.16 ± 0.2 IU/l) levels during T treatment were suppressed. Pretreatment melatonin levels in IGD were greater than those in age-matched pubertal controls while in KS, melatonin levels were lower than values in controls. Melatonin levels were equal in all 12 hypogonadal patients and controls when T levels were well matched. Mean (±SD) dark-time melatonin levels decreased from 286 ± 18 to 157 ± 26 pmol/l in IGD and increased from 92 ± 19 to 183 ± 48 pmol/l in KS (vs 178 ± 59 pmol/l in controls). The integrated melatonin values decreased in IGD (from 184 ± 14 to 102 ± 21 pmol/min. l × 103) and increased in KS (from 64 ± 13 to 123 ± 40, vs. 116 ± 39 pmol/min. l × 103 in controls). No correlations were found between melatonin and LH, FSH or E2 levels.
CONCLUSIONS
These data indicate that male patients with GnRH deficiency have increased nocturnal melatonin secretion while in hypergonadotrophic hypogonadal males melatonin secretion is decreased. Testosterone treatment normalized melatonin concentrations in these patients. Taken together, the results suggest that GnRH, gonadotrophins and gonadal steroids modulate pineal melatonin in humans.
Now you are probably thinking that this still doesn't make much sense. It will in a moment. Melatonin has been shown to be a very potent anti-aging and antioxidant peptide-hormone. One of the main pathways for this ability is through liver enzyme production, especially glutathione levels. Within 90 minutes of melatonin production there was a marked increase of over 100% of glutathione activity. This can be seen here:
Melatonin stimulates the activity of the detoxifying enzyme glutathione peroxidase in several tissues of chicks
Marta I. Pablos, 1 Maria T. Agapito, 1 Regina Gutierrez, 1 Jose M. Recio, 1 Russel J. Reiter, 2 Lornell Barlow-Walden, 2 Dario Acuña-Castroviejo, 3 Armando Menendez-Pelaez 4
1 Department of Biochemistry, Molecular Biology and Physiology, Facultad de Ciencias, Universidad de Valladolid, Valladolid, Spain 2 Department of Cellular and Structural Biology, The Health Science Center at San Antonio, San Antonio, TX USA 3 Department of Physiology, Facultad de Medicina, University of Granada, Granada, Spain 4 Department of Morphology and Cellular Biology, University of Oviedo, Oviedo, Spain
ABSTRACT
Abstract: The pineal hormone melatonin has been shown to directly scavenge free radicals and to stimulate, in the mammalian brain, at least one enzyme, glutathione peroxidase, which reduces free radical generation. In the present studies, we examined the effect of melatonin on glutathione peroxidase activity in several tissues of an avian species. Melatonin (500 μg/kg), when injected into chicks, increased glutathione peroxidase activity within 90 min in every tissue examined. Tissue melatonin levels, measured by radioimmunoassay, also increased following its peripheral administration. Depending on the tissue, the measured increases in melatonin varied from 75% to 1,300% over the control values. The melatonin-induced increases in glutathione peroxidase activity varied with the tissue and were between 22% and 134%. These percentage increases in glutathione peroxidase activity were directly correlated with tissue melatonin content. These results suggest that melatonin induces the activity of the detoxifying enzyme, glutathione peroxidase, in several tissues in the chick. The findings also suggest that melatonin would reduce the generation of highly toxic hydroxyl radicals by metabolizing its precursor, hydrogen peroxide. Because of this ability to stimulate glutathione peroxidase activity, melatonin should be considered as a component of the antioxidative defense system in this avian species.
With this being said it would be better to keep your dosages to the morning and afternoon. It has been argued before that, "I don't take melatonin" and "but testosterone levels are highest in the morning". Melatonin is produced naturally and is responsible for your circadian rhythms (biological clock), supplementation will further increase levels of glutathione and other liver enzymes and a lot of people who supplement with anabolics use melatonin. To the second statement while taking anabolics natural hormones are often extremely low so taking them at any point during the day will make it the dominant hormone. Depending on when you go to sleep this could change.
