14 replies to this topic

[wydell]

We can refer back to this thread for som discussion on this topic

http://www.imminst.o...=0

I made a separate thread for the purposes of comparing Mel to Res

Possible Melatonin Benefits vs. Res

- Dirt Cheap

- Good for people who want take some risk with a supplement for a potential benefit, but don't want to shell out bigger bucks for res.

- Subjectively feels like it is doing something to me. This is personal to me because Melatonin does put put me to sleep. With res, I don't notice anything. ( I will point out that this is not necessarily a benefit. Maybe it's more a less a personal subjective vote of confidence. And it might add to a placebo effect, at least personally for me.)

- Maybe Mel is more bioavailable than Res? It would not surprise me as it seems to me to have a more definitive effect on people than Res. (Again, I don't know if this in fact a benefit or if this is in fact true. It's my perception.)

- Might not require large doses. Does anyone know what a scaled up human dose would be from the Melatonin mice studies? (Again, I don't know if this in fact a benefit)




Possible Res Benefits Vs Mel

- I think the animals lived longer on Res than the Melatonin Mice

- Purported Super Athlete effect of the mice from Res. Though I know of no human reporting doubled endurance from Res or anything close to doubled endurance.



I take both res and melatonin, so I roll the dice with both.

By the way, I thought this was a pretty good article on Melatonin:

http://www.healthy.n...Id=1234&xcntr=1

[Mind]

Both supps do different things within the body so it is hard to compare. However, based on early results from t-res and long term studies with melatonin, they both seem to offer 'some' benefits for very low risk.

[whitenoise]

A human melatonin dose is about 1 mg. You can dose significantly higher, studies have gone as high as 50 mg that I know of, however there's a reverse dose effect curve, so higher doses weaken the somnolence effect. I suppose that could be a good thing if you want to use large doses for other benefits. Not sure how that would affect sleep cycles though.

What risks are associated with melatonin? I've not heard much about dangerous side effects.

[lucid]

There was some meta-analysis of melatonin studies which found that melatonin life-extension claims were un-proven.
I believe someone said in that discussion that if you filtered out studies where melatonin was given at a ceratin (lowish) doses and only at night, then the results were much better looking.
I also have read a study that refuted the claim that melatonin levels drop in our bodies as we age. I'm not certain of any resolution on this issue.

While they are both seem pretty low risk, I think T-resv is much more likely to extend maximal lfespan. But I take both

[whitenoise]

I was just thinking of "risk" as "bad things happening". Not extending life-span doesn't make it risky in my mind. Melatonin is a powerful suicidal antioxident though, so it probably does have some positive effects on average life span

Doesn't the pituary gland calcify as we age? I thought the decrease in melatonin levels as age increase was pretty solid.

[biknut]

I haven't taken Melatonin for very long, only about a month, but it's had a big effect on my sleep.

I'm 53, and for about the last 10 years the quality of my sleep has gone downhill. What was happening is when I go to bed, usually about 1 am, I wake up every night around 4 or 5 am wide awake. Then about 7:30 I get sleepy again.

I decided to try Now brand 3 mg. Used to be, I would only have a good nights sleep maybe 1 night in 3 months. Now when I go to bed I fall asleep right away and never see the clock again till about 8 am. The same thing happens almost every night now.

I think this has to have a positive effect on my health.

[lucid]

I was just thinking of "risk" as "bad things happening".  Not extending life-span doesn't make it risky in my mind.  Melatonin is a powerful suicidal antioxident though, so it probably does have some positive effects on average life span

Doesn't the pituary gland calcify as we age?  I thought the decrease in melatonin levels as age increase was pretty solid.

Well lots of the melatonin studies reported a decrease in lifespan. As said before those maybe just studies where melatonin was administered during the entire day. I'll go and dig up old studies and refamiliarize myself with the material.

[wydell]

I was just thinking of "risk" as "bad things happening".  Not extending life-span doesn't make it risky in my mind.  Melatonin is a powerful suicidal antioxident though, so it probably does have some positive effects on average life span

Doesn't the pituary gland calcify as we age?  I thought the decrease in melatonin levels as age increase was pretty solid.

Well lots of the melatonin studies reported a decrease in lifespan. As said before those maybe just studies where melatonin was administered during the entire day. I'll go and dig up old studies and refamiliarize myself with the material.

I read about one study showing a decrease in lifespan, but in that study melatonin was given to younger mice as opposed to older mice. The article indicated that the mice were less than 12 months old and that a less than 12 year old mouse might scale to a human being less than 35 for comparison purposes. You can read about it in the article link in the intro post. The article did not recommend melatonin for life extension.

[dannov]

http://www.google.co...ing&btnG=Search

http://scholar.googl...F-8&oi=scholarr

I had a friend (Jaime Ochoa, you'll see J. Ochoa in the results) in his 40s that was in some way related to a melatonin/seratonin study much earlier in his life. He claimed that the doctor was the subject in the study, and wanted to prove to the world that through nightly lisenge melatonin supplementation, that he'd prevent aging. He would crack open a melatonin pill and simply put the powder underneath his tongue, turn the lights out, and go to sleep (this was before bed). He's supposedly been doing this for decades and appears to have not aged at all. I should try to get in contact with Jaime again and see if I can get more information.

*edit* -- 2nd link you can see "J. Ochoa"

[krillin]

lisenge

Do you mean lozenge?

Here's some recent evidence that melatonin metabolite excretion declines with age, and that as you get older there's less difference between night and day, unless you're going to live beyond a century.

Exp Gerontol. 2007 Jul 4;
Neuroendocrine features in extreme longevity.
Ferrari E, Cravello L, Falvo F, Barili L, Solerte SB, Fioravanti M, Magri F; the Italian Multicenter Study on Centenarians.
Department of Internal Medicine and Medical Therapy, Geriatrics Unit, University of Pavia, Via Emilia 12, 27100 Pavia, Italy.

In order to evaluate the effects of some neuro-endocrine changes during aging we have studied adrenal, thyroid and pineal secretion in young, healthy old and centenarians. The number of subjects in each hormone group varied.The following parameters were evaluated: serum levels of cortisol, dehydroepiandrosterone-sulfate (DHEAS), free triiodothyronine (FT3), thyroxine (FT4), reverse triiodothyronine (rT3) and thyroid-stimulating hormone (TSH). Urinary 6-hydroxymelatonin sulfate (aMT6s) and free cortisol were measured twice daily.Centenarians exhibited significantly lower TSH levels together with slightly higher rT3 levels than old controls. These changes could be due to reduced 5'-deiodinase activity occurring also in absence of substantial changes of the nutritional pattern.Morning serum cortisol levels were found to be similar in the 3 age groups, whereas the decline of serum DHEAS levels was well evident also after the ninth decade of life. The cortisol/DHEAS molar ratio, which usually increases with age and considered to be an expression of a neurotoxic pattern of the steroidal milieu in the central nervous system, did not shown any further increase in centenarians. The urinary free cortisol and aMT6s excretion declined with age; however only in centenarians and in young controls aMT6s excretion was significantly higher at night than during the day. These findings suggest that the circadian rhythm of melatonin secretion is maintained in centenarians and, based on the limitations of this study, could be considered one factor in successful aging.

PMID: 17764865

[dannov]

lisenge

Do you mean lozenge?

Here's some recent evidence that melatonin metabolite excretion declines with age, and that as you get older there's less difference between night and day, unless you're going to live beyond a century.

Exp Gerontol. 2007 Jul 4;
Neuroendocrine features in extreme longevity.
Ferrari E, Cravello L, Falvo F, Barili L, Solerte SB, Fioravanti M, Magri F; the Italian Multicenter Study on Centenarians.
Department of Internal Medicine and Medical Therapy, Geriatrics Unit, University of Pavia, Via Emilia 12, 27100 Pavia, Italy.

In order to evaluate the effects of some neuro-endocrine changes during aging we have studied adrenal, thyroid and pineal secretion in young, healthy old and centenarians. The number of subjects in each hormone group varied.The following parameters were evaluated: serum levels of cortisol, dehydroepiandrosterone-sulfate (DHEAS), free triiodothyronine (FT3), thyroxine (FT4), reverse triiodothyronine (rT3) and thyroid-stimulating hormone (TSH). Urinary 6-hydroxymelatonin sulfate (aMT6s) and free cortisol were measured twice daily.Centenarians exhibited significantly lower TSH levels together with slightly higher rT3 levels than old controls. These changes could be due to reduced 5'-deiodinase activity occurring also in absence of substantial changes of the nutritional pattern.Morning serum cortisol levels were found to be similar in the 3 age groups, whereas the decline of serum DHEAS levels was well evident also after the ninth decade of life. The cortisol/DHEAS molar ratio, which usually increases with age and considered to be an expression of a neurotoxic pattern of the steroidal milieu in the central nervous system, did not shown any further increase in centenarians. The urinary free cortisol and aMT6s excretion declined with age; however only in centenarians and in young controls aMT6s excretion was significantly higher at night than during the day. These findings suggest that the circadian rhythm of melatonin secretion is maintained in centenarians and, based on the limitations of this study, could be considered one factor in successful aging.

PMID: 17764865

Lozenge ya, knew I was misspelling that. :(

[maestro949]

I also have read a study that refuted the claim that melatonin levels drop in our bodies as we age.

Do you recall the source? I've only seen research that indicates a decline with age.

[lucid]

I also have read a study that refuted the claim that melatonin levels drop in our bodies as we age.


Do you recall the source? I've only seen research that indicates a decline with age.

Article: http://www.pubmedcen...25257#id2696677 references articles in support and in disagreement with the change in melatonin production with age.
Here are two studies showing that Melatonin production does not decrease with age:

Am J Med. 1999 Nov;107(5):432-6.Click here to read  Links

    Comment in:
        Am J Med. 2000 Sep;109(4):343-5.

    Do plasma melatonin concentrations decline with age?

        * Zeitzer JM,
        * Daniels JE,
        * Duffy JF,
        * Klerman EB,
        * Shanahan TL,
        * Dijk DJ,
        * Czeisler CA.

    Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.

    PURPOSE: Numerous reports that secretion of the putative sleep-promoting hormone melatonin declines with age have led to suggestions that melatonin replacement therapy be used to treat sleep problems in older patients. We sought to reassess whether the endogenous circadian rhythm of plasma melatonin concentration changes with age in healthy drug-free adults. METHODS: We analyzed the amplitude of plasma melatonin profiles during a constant routine in 34 healthy drug-free older subjects (20 women and 14 men, aged 65 to 81 years) and compared them with 98 healthy drug-free young men (aged 18 to 30 years). RESULTS: We could detect no significant difference between a healthy and drug-free group of older men and women as compared to one of young men in the endogenous circadian amplitude of the plasma melatonin rhythm, as described by mean 24-hour average melatonin concentration (70 pmol/liter vs 73 pmol/liter, P = 0.97), or the duration (9.3 hours vs 9.1 hours, P = 0.43), mean (162 pmol/liter vs 161 pmol/liter, P = 0.63), or integrated area (85,800 pmol x min/liter vs 86,700 pmol x min/liter, P = 0.66) of the nocturnal peak of plasma melatonin. CONCLUSION: These results do not support the hypothesis that reduction of plasma melatonin concentration is a general characteristic of healthy aging. Should melatonin replacement therapy or melatonin supplementation prove to be clinically useful, we recommend that an assessment of endogenous melatonin be carried out before such treatment is used in older patients.

    PMID: 10569297 [PubMed - indexed for MEDLINE]

Melatonin secretion occurs at a constant rate in both young and older men and women.
Fourtillan JB, Brisson AM, Fourtillan M, Ingrand I, Decourt JP, Girault J.

CEMAF s.a., 86000 Poitiers, France.

The magnitude and duration of melatonin (MLT) secretion were measured over a period of 25 h with pharmacokinetic studies employing administration of D(7) MLT at midday and at midnight in two separate studies and two groups of subjects, 12 young and 11 older men and women. Plasma levels of endogenous MLT and D(7) MLT were quantified separately by use of a specific and sensitive method (gas chromatography-mass spectrometry) previously developed in our laboratory, enabling us to measure endogenous and exogenous MLT levels down to 0.5 pg/ml in plasma. In the two groups of subjects, MLT secretion occurred only at night: onset time of secretion was from 1915 to 2205 (Greenwich mean time), and offset was from 0305 to 0545. No MLT peak was observed in individual nocturnal MLT profiles that were similar to curves obtained for a rate-constant infusion. Modelization demonstrated the superimposition of observed data and simulated curves. MLT concentrations decreasing from the offset of secretion might correspond to the elimination of MLT present in the body at the end of nocturnal secretion. By use of the MLT clearance given by pharmacokinetics, the amount of secreted MLT was found to be 35.7 and 21.6 microg for men and women, respectively, and the rate of secretion was 4.6 and 2.8 microg/h, respectively. No significant gender difference was observed for these two parameters when normalized to body weight. No significant gender difference was observed for onset times of secretion or duration of secretion (7.6-8.6 h) within the two groups, or between young and older subjects.

While the first article was published in 2005, I was unable to find a referenced article (60-66 in their citations) that was published after Melatonin secretion occurs at a constant rate in both young and older men and women and Do plasma melatonin concentrations decline with age? which offered comparable evidence of decline in melatonin production with age. In fact one of the studies in the citation group supposed to support the theory that endrogenous melatonin production declined with age showed that Old people exposed to bright light for 4 hours during the day could regain the melatonin nocturnal melatonin production of the young control group (Implying that melatonin production is more of an environment issue than an aging issue). Here is said study:

Diminished melatonin secretion in the elderly caused by insufficient environmental illumination.
Mishima K, Okawa M, Shimizu T, Hishikawa Y.

Department of Neuropsychiatry, Akita University School of Medicine, Akita City 010-8543, Japan. mishima@psy.med.akita-u.ac.jp

The pineal hormone melatonin has some circadian regulatory effects and is assumed to have a close relation with sleep initiation and maintenance. Many previous reports have described age-related decreases in melatonin levels, especially in elderly insomniacs (EIs), which may act as causal or exacerbating factors in sleep disturbances in the elderly. Ten elderly residents with psychophysiological insomnia (mean age, 74.2 yr), 10 healthy residents of the same home [elderly control (EC) group; mean age, 72.7 yr], and 10 healthy young control subjects (mean age, 20.9 yr) living at home participated in this study. The elderly persons, especially the EIs, were exposed to significantly less environmental light and simultaneously suffered from significantly diminished nocturnal melatonin secretion. Supplementary exposure to 4 h (1000 to 1200 h, 1400 to 1600 h) of midday bright light in the EI group significantly increased melatonin secretion to levels similar to those in the young control group without circadian phase-shifting. There was a tendency for the magnitude of the increase in nocturnal melatonin secretion stimulated by bright light to parallel amelioration of sleep disturbances in these subjects. The present findings suggest that we need to pay attention to elderly individuals who suffer under conditions of poor environmental light resulting in disorganized circadian rhythms, including the sleep-wake cycle.

PMID: 11231989 [PubMed - indexed for MEDLINE]

Ill post the meta-analysis of lifespan increases and decreases in a bit.

[biknut]

This could be a good explaination of how Melatoinin increases lifespan.

Lack of sleep may be deadly, research shows

September 24, 2007 06:39:50 AM PST

People who do not get enough sleep are more than twice as likely to die of heart disease, according to a large British study released on Monday.

Although the reasons are unclear, researchers said lack of sleep appeared to be linked to increased blood pressure, which is known to raise the risk of heart attacks and stroke.

A 17-year analysis of 10,000 government workers showed those who cut their sleeping from seven hours a night to five or less faced a 1.7-fold increased risk in mortality from all causes and more than double the risk of cardiovascular death.

The findings highlight a danger in busy modern lifestyles, Francesco Cappuccio, professor of cardiovascular medicine at the University of Warwick's medical school, told the annual conference of the British Sleep Society in Cambridge.

"A third of the population of the UK and over 40 percent in the U.S. regularly sleep less than five hours a night, so it is not a trivial problem," he said in a telephone interview.

"The current pressures in society to cut out sleep, in order to squeeze in more, may not be a good idea -- particularly if you go below five hours."

Previous research has highlighted the potential health risks of shift work and disrupted sleep. But the study by Cappuccio and colleagues, which was supported by British government and U.S. funding, is the first to link duration of sleep and mortality rates.

The study looked at sleep patterns of participants aged 35-55 years at two points in their lives -- 1985-88 and 1992-93 -- and then tracked their mortality rates until 2004.

The results were adjusted to take account of other possible risk factors such as initial age, sex, smoking and alcohol consumption, body mass index, blood pressure and cholesterol.

The correlation with cardiovascular risk in those who slept less in the 1990s than in the 1980s was clear but, curiously, there was also a higher mortality rate in people who increased their sleeping to more than nine hours.

In this case, however, there was no cardiovascular link and Cappuccio said it was possible that longer sleeping could be related to other health problems such as depression or cancer-related fatigue.

"In terms of prevention, our findings indicate that consistently sleeping around seven hours per night is optimal for health," he said.

http://health.yahoo.com/news/179663

[lucid]

Here is the review, I promised I would find: (full text available)
http://www.ingentaco...000006/art00002

The results of studies on the effect of pineal indole hormone melatonin on the life span of mice, rats, fruit flies, and worms are critically reviewed. In mice, long-term administration of melatonin was followed by an increase in their life span in 12 experiments and had no effect in 8 of 20 different experiments. In D. melanogaster, the supplementation of melatonin to the nutrient medium during developmental stages gave contradictory results, but when melatonin was added to food throughout the life span, an increase in the longevity of fruit flies has been observed. Melatonin decreased the survival of C. elegans but increased the clonal life span of planaria Paramecium tertaurelia. Available data suggest antioxidant and atherogenic effects of melatonin. Melatonin alone turned out to be neither toxic nor mutagenic in the Ames test and revealed clastogenic activity in high concentration in the COMET assay. Melatonin inhibits mutagenesis induced by irradiation and by indirect chemical mutagens and inhibits the development of spontaneous and chemical-induced tumors in mice and rats. Further studies and clinical trials are needed to verify that melatonin is both safe and has geroprotector efficacy for humans.

Page 5 has a good summary of the results of mice studies. The results are pretty symmetrical. A fair number good and a fair number are bad. I wasn't able to dissect a clear pattern for what experimental controls would produce an increase in lifespan. Perhaps someone is more familiar with a better review.