heres some good posts from the sci.life-extension forum. The author takes 30 mg melatonin a night. I might be upping my dose soon too.
comments?
http://groups.google...a51f30857ff?tvc1. tcart...@elp.rr.com Oct 13, 11:59 pm
Newsgroups: sci.life-extension
From: tcart...@elp.rr.com - Find messages by this author
Date: 13 Oct 2005 15:59:09 -0700
Hi,
Endocrine. 2005 Jul;27(2):131-6. Related Articles, Links
Metabolic effects of melatonin on oxidative stress and diabetes
mellitus.
Nishida S.
Department of Biochemistry, Nihon University School of Medicine, Tokyo
173-8610, Japan.
Melatonin, which is synthesized in the pineal gland and
other tissues, has a variety of physiological, immunological, and
biochemical functions. It is a direct scavenger of free radicals and
has indirect antioxidant effects due to its stimulation of the
expression and activity of antioxidative enzymes such as glutathione
peroxidase, superoxide dismutase and catalase, and NO synthase, in
mammalian cells. Melatonin also reduces serum lipid levels in mammalian
species, and helps to prevent oxidative stress in diabetic subjects.
Long-term melatonin administration to diabetic rats reduced their
hyperlipidemia and hyperinsulinemia, and restored their altered ratios
of polyunsaturated fatty acid in serum and tissues. It was recently
reported that melatonin enhanced insulin-receptor kinase and IRS-1
phosphorylation, suggesting the potential existence of signaling
pathway cross-talk between melatonin and insulin. Because TNF-alpha has
been shown to impair insulin action by suppressing insulin
receptor-tyrosine kinase activity and its IRS-1 tyrosine
phosphorylation in peripheral tissues such as skeletal muscle cells, it
was speculated that melatonin might counteract TNF-alpha-associated
insulin resistance in type 2 diabetes. This review will focus on the
physiological and metabolic effects of melatonin and highlight its
potential use for the treatment of cholesterol/lipid and carbohydrate
disorders.
PMID: 16217126
[Highly speculative at this stage, but melatonin should help whether
or not it's "especially" helpful for diabetics or not. Clinical
trials are showing that consistent human benefits start at about the
level of 20 mg/day. I'm now taking 30.]
6. tcart...@elp.rr.com Oct 15, 2:47 am show options
Newsgroups: sci.life-extension
From: tcart...@elp.rr.com - Find messages by this author
Date: 14 Oct 2005 18:47:43 -0700
Hi George,
Twenty mg is a woefully small dose, as seen by the number of
deaths in cancer trials of people who only took this much. With the
decrease of fatalities in these trials, and the fact that absorption
varies by as much as 3500%, we can easily surmise that more lives would
have been saved if larger doses had been used, or if the doctors had
titrated to some given plasma level. Note that I stated the benefits
START at 20 mg. The most successful trial gave 75 mg for six months or
more. It was a contraceptive study. Moderate Alzheimer's effects have
been seen at just 9 mg, a level which is of no value whatsoever for
many. I have yet to see a null study on cancer at 20 mg, but many show
less effect than the ones I post below.
Your recommendation on dosage was initiated at .3 mg by the
man that holds the patent on that dose. Those recommendations are now
badly dated. We live in a medical environment of VERY rapid progress.
The cancer work is on a wide variety of very common cancers,
and makes melatonin the single most effective therapy for cancer
prevention and treatment. Many large trials are ongoing and they could
of course negate or attenuate the current status of melatonin as number
one. Of course it is seldom used at this time, but its use is
increasing at a rapid pace.
A large six year Russian trial gave a 400% reduction in
mortality for the use of two peptides that increase melatonin levels.
Recent work is suggesting that another pineal product given with
melatonin will result in additional benefits. I think a clinical trial
is planned.
In vitro and animal work very strongly supports the clinical
trials, and suggests other benefits such as life extension. 12 of 20
rodent studies showed a life extension of about 20%. Many of the null
studies may have used doses too low or strains of mice that didn't
absorb well.
Anyone who is unconvinced should search this group for
melatonin with my name as author. I've made many fully referenced
posts.
Thomas
According to "Melatonin" (R.J.Reiter + J.Robinson)
``In one study five healthy young people took the same 2mg dose of
Melatonin. Among the participants there was a 35-fold difference
in the amount of melatonin that enters the bloodstream.'' - p.301.
Clin Endocrinol (Oxf). 2001 Mar;54(3):339-46. (Maybe I should try
sublingual)
J Pineal Res. 2003 Aug;35(1):12-5.
Support Care Cancer. 2002 Mar;10(2):110-6. Epub 2001 Nov 13. Related
Articles, Links
Is there a role for melatonin in supportive care?
Lissoni P.
U.O. di Oncologia Medica e Radioterapia, Ospedale S. Gerardo dei
Tintori, 20052 Monza (MI), Italy. oncolo...@genie.it
Melatonin (MLT) is the main hormone released from the
pineal gland and has proved to have physiological antitumor activity.
MLT has been shown to exert anticancer activity through several
biological mechanisms: antiproliferative action, stimulation of
anticancer immunity, modulation of oncogene expression, and
anti-inflammatory, anti-oxidant and anti-angiogenic effects. Several
experimental studies have shown that MLT may inhibit cancer cell
growth, and preliminary clinical studies seem to confirm its anticancer
property in humans. In addition, MLT may have other biological effects,
which could be useful in the palliative therapy of cancer, namely
anticachectic, anti-asthenic and thrombopoietic activities. On this
basis, the present clinical investigation was performed in an attempt
at better definition of the therapeutic properties of MLT in human
neoplasms. In a first clinical study, we evaluated the effects of MLT
in a group of 1,440 patients with untreatable advanced solid tumors,
who received supportive care alone or supportive care plus MLT. In a
second study, we evaluated the influence of MLT on the efficacy and
toxicity of chemotherapy in a group of 200 metastatic patients with
chemotherapy-resistant tumor histotype, who were randomized to receive
chemotherapy alone or chemotherapy plus MLT. In both studies, MLT was
given orally at 20 mg/day during the dark period of the day. The
frequency of cachexia, asthenia, thrombocytopenia and lymphocytopenia
was significantly lower in patients treated with MLT than in those who
received supportive care alone. Moreover, the percentage of patients
with disease stabilization and the percentage 1-year survival were both
significantly higher in patients concomitantly treated with MLT than in
those treated with supportive care alone. The objective tumor response
rate was significantly higher in patients treated with chemotherapy
plus MLT than in those treated with chemotherapy alone. Moreover, MLT
induced a significant decline in the frequency of chemotherapy-induced
asthenia, thrombocytopenia, stomatitis, cardiotoxicity and
neurotoxicity. These clinical results demonstrate that the pineal
hormone MLT may be successfully administered in medical oncology in the
supportive care of untreatable advanced cancer patients and for the
prevention of chemotherapy-induced toxicity. PMID: 11862501
--------------------------------------------------------------------------------
4: Eur J Cancer. 1999 Nov;35(12):1688-92. Related Articles, Links
Decreased toxicity and increased efficacy of cancer chemotherapy using
the pineal hormone melatonin in metastatic solid tumour patients with
poor clinical status.
Lissoni P, Barni S, Mandala M, Ardizzoia A, Paolorossi F, Vaghi M,
Longarini R, Malugani F, Tancini G.
Division of Radiation Oncology, S. Gerardo Hospital, Monza, Milan,
Italy.
Melatonin (MLT) has been proven to counteract chemotherapy
toxicity, by acting as an anti-oxidant agent, and to promote apoptosis
of cancer cells, so enhancing chemotherapy cytotoxicity. The aim of
this study was to evaluate the effects of concomitant MLT
administration on toxicity and efficacy of several chemotherapeutic
combinations in advanced cancer patients with poor clinical status. The
study included 250 metastatic solid tumour patients (lung cancer, 104;
breast cancer, 77; gastrointestinal tract neoplasms, 42; head and neck
cancers, 27), who were randomized to receive MLT (20 mg/day orally
every day) plus chemotherapy, or chemotherapy alone. Chemotherapy
consisted of cisplatin (CDDP) plus etoposide or gemcitabine alone for
lung cancer, doxorubicin alone, mitoxantrone alone or paclitaxel alone
for breast cancer, 5-FU plus folinic acid for gastro-intestinal tumours
and 5-FU plus CDDP for head and neck cancers. The 1-year survival rate
and the objective tumour regression rate were significantly higher in
patients concomitantly treated with MLT than in those who received
chemotherapy (CT) alone (tumour response rate: 42/124 CT + MLT versus
19/126 CT only, P < 0.001; 1-year survival: 63/124 CT + MLT versus
29/126 CT only, P < 0.001). Moreover, the concomitant administration of
MLT significantly reduced the frequency of thrombocytopenia,
neurotoxicity, cardiotoxicity, stomatitis and asthenia. This study
indicates that the pineal hormone MLT may enhance the efficacy of
chemotherapy and reduce its toxicity, at least in advanced cancer
patients of poor clinical status. PMID: 10674014
Five years survival in metastatic non-small cell lung cancer patients
treated
with chemotherapy alone or chemotherapy and melatonin: a randomized
trial.
Lissoni P, Chilelli M, Villa S, Cerizza L, Tancini G.
Divisione di Radioterapia Oncologica, Ospedale San Gerardo, Monza,
Milan, Italy.
p.liss...@hsgerardo.org
Numerous experimental data have documented the
oncostatic properties of
melatonin. In addition to its potential direct antitumor activity,
melatonin has
proved to modulate the effects of cancer chemotherapy, by enhancing its
therapeutic efficacy and reducing its toxicity. The increase in
chemotherapeutic
efficacy by melatonin may depend on two main mechanisms, namely
prevention of
chemotherapy-induced lymphocyte damage and its antioxidant effect,
which has
been proved to amplify cytotoxic actions of the chemotherapeutic agents
against
cancer cells. However, the clinical results available at present with
melatonin
and chemotherapy in the treatment of human neoplasms are generally
limited to
the evaluation of 1-year survival in patients with very advanced
disease. Thus,
the present study was performed to assess the 5-year survival results
in
metastatic non-small cell lung cancer patients obtained with a
chemotherapeutic
regimen consisting of cisplatin and etoposide, with or without the
concomitant
administration of melatonin (20 mg/day orally in the evening). The
study
included 100 consecutive patients who were randomized to receive
chemotherapy
alone or chemotherapy and melatonin. Both the overall tumor regression
rate and
the 5-year survival results were significantly higher in patients
concomitantly
treated with melatonin. In particular, no patient treated with
chemotherapy
alone was alive after 2 years, whereas a 5-year survival was achieved
in three
of 49 (6%) patients treated with chemotherapy and melatonin. Moreover,
chemotherapy was better tolerated in patients treated with melatonin.
This study
confirms, in a considerable number of patients and for a long follow-up
period,
the possibility to improve the efficacy of chemotherapy in terms of
both
survival and quality of life by a concomitant administration of
melatonin. This
suggests a new biochemotherapeutic strategy in the treatment of human
neoplasms.
PMID: 12823608
[This is one of many positive trials. Click on related articles.]
And none titrated the dosage. Had blood levels been checked at least it
would have been known whether or not nonresponders had good adsorption
or not. And they might well have been able to get much better results
with titration to a given concentration. Are these people incompetent,
or am I missing something?]