#407

I took every melatonin study in this thread and fed it into ChatGPT and got it to spit out a summary of all of them:

:dna: Core Biological Roles of Melatonin

1. Circadian Regulation

  • Melatonin is primarily secreted by the pineal gland and plays a key role in synchronizing circadian rhythms.
  • It follows a light-dependent cycle, peaking at night and signaling darkness to the body, thereby promoting sleep and regulating hormonal cycles (including cortisol and reproductive hormones).

2. Mitochondrial Health & Energy Metabolism

  • Melatonin is synthesized not only in the pineal gland but also in mitochondria.
  • Studies show it enhances mitochondrial function by:
    • Promoting ATP production.
    • Reducing mitochondrial oxidative stress.
    • Improving mitochondrial calcium homeostasis.
  • It can stimulate muscle fiber conversion (from glycolytic to oxidative) in diabetic models—mimicking some effects of endurance exercise.

3. Antioxidant & Free Radical Scavenging

  • Melatonin directly scavenges reactive oxygen and nitrogen species.
  • It also upregulates endogenous antioxidant enzymes (e.g., SOD, glutathione peroxidase).
  • Unique among antioxidants, it crosses the blood-brain barrier and concentrates in mitochondria and nuclei.

:brain: Neuroprotection & Brain Health

4. Alzheimer’s & Parkinson’s Disease

  • Melatonin reduces tau hyperphosphorylation and Aβ accumulation in animal models.
  • Enhances glymphatic clearance of metabolic waste, possibly reducing risk of neurodegeneration.
  • Supports mitochondrial integrity in neurons and may help counter age-related metabolic shifts in brain cells.

5. Cognitive Function & Memory

  • Improves long-term memory formation in rodents via modulation of protein phosphorylation.
  • Enhances glymphatic function post-intracerebral hemorrhage, resulting in improved cognitive recovery.

:person_in_lotus_position: Sleep and Chronobiology

6. Sleep Quality

  • Meta-analyses show optimal efficacy for:
    • 3–4 mg taken ~3 hours before bedtime.
    • Helps reduce sleep onset latency and increase total sleep time.
  • Especially effective in older adults and those with insomnia or circadian rhythm disorders.

7. Jet Lag, Shift Work, and Chronotherapy

  • Well-suited for shifting circadian phase in cases of jet lag and shift work.
  • Has been studied as a tool in chronotherapy to align medication administration with biological rhythms.

:heartbeat: Cardiovascular & Metabolic Health

8. Blood Pressure Regulation

  • Reduces nocturnal blood pressure (more in “non-dippers”), possibly via improved endothelial function and oxidative stress reduction.

9. Glucose Metabolism and Diabesity

  • In diabetic models:
    • Enhances insulin sensitivity.
    • Supports healthy skeletal muscle function.
    • Promotes metabolic reprogramming of muscle and liver.

:eye: Retinal and Ocular Health

10. Age-Related Macular Degeneration (AMD)

  • Protects retinal pigment epithelial (RPE) cells by:
    • Inhibiting necroptosis.
    • Suppressing NLRP3 inflammasome via the SIRT1/Nrf2 pathway.
  • Preserves retinal structure in AMD models.

:microbe: Immune Modulation

11. Dual Immunoregulation

  • Acts as an immune buffer:
    • Stimulates immunity in immunosuppressed states.
    • Suppresses excessive inflammation during cytokine storms.
  • Reduces IL-6 and TNF-α while promoting IL-10 and T-reg activity.
  • Shown to modulate macrophage activity via NF-κB and AA-NAT upregulation.

12. Applications in Autoimmune and Infectious Disease

  • May help in autoimmune diseases and as an adjunct in viral infections (e.g., COVID-19) by dampening hyperinflammation while preserving immune competence.

:dna: Anti-Aging and Lifespan Extension

13. Lifespan Studies

  • Melatonin extended lifespan in several animal models (e.g., flies, mice, aquatic invertebrates), possibly due to its mitochondrial and antioxidant actions.
  • Highlighted in DrugAge as a candidate longevity agent.

14. Aging Phenotypes

  • Maintains mitochondrial and glymphatic function with age.
  • Prevents pathological metabolic reprogramming in aged neurons.

:test_tube: Cancer and Cell Growth

15. Anticancer Activity

  • Shown to inhibit proliferation in some cancer cell lines.
  • May sensitize tumors to chemotherapy while protecting normal cells from side effects (radioprotective and antioxidant roles).

:warning: Safety, Risks, and Considerations

16. Generally Safe — But Not Always Benign

  • Very high doses (up to 200 mg/day) used in research with minimal side effects reported.
  • Most common mild side effects: vivid dreams, morning grogginess, headaches.

17. Rare Case Reports

  • One case report linked melatonin to ventricular arrhythmias (PVCs), which resolved after stopping supplementation — indicates rare individual susceptibility.

18. Hormonal & Developmental Considerations

  • Low melatonin levels in children with hypothalamic hamartomas were linked to precocious puberty, suggesting a role in reproductive timing.

Summary: The Case for Melatonin

Melatonin is a pleiotropic molecule:

  • Antioxidant, immunomodulator, chronobiotic, and neuroprotective agent.
  • It impacts systems far beyond sleep, including metabolism, immunity, cognition, mitochondrial health, and aging.
  • Therapeutically, it is among the most underrated low-toxicity compounds with broad potential — though rare risks exist and personalization is warranted.
2 Likes
#408

Which tends to demonstrate both the strengths and weaknesses of LLMs. The LLM does not have a model of reality so cannot easily identify what is really important. On the other hand most human beings don’t have the knowledge to analyse the input.

#409

I spoon a 1/4 teaspoon of powder into my mouth, drink some water, swish it around, swallow, and drink a bit more water.

Seems to get it down without too much terrible taste exposure.

1 Like
#411

how many mg is a quarter teaspoon?

#412

I tried to down 1/2 teaspoon… Hoping to increase to 1 teaspoon. (About 1.5g)

It will take be a while to tolerate it. It doesn’t dissolve in water. Maybe I’ll try evoo.

#413

I estimate 775 mg to 800 mg.

1 Like
#414

Mine dissolves in water enough to swallow, and it’s from two different sources. I put the dose in a small amount of water (less than a shot) stir it well with a teaspoon, leave it for 30 mins then stir again, and it goes down fine. There is usually some residue left that I swill another small amount of water and swallow it down, which also helps with any slight burning sensations. This is about 40 mins before bedtime.

#415

I got 100g from Pure Bulk. I’m not noticing any particularly bad taste. It’s slightly bitter. Maybe I’m just used to eating horrible tasting herbs (tongkat ali for instance).

1 Like
#416

I’ve just bumped up to 1/2 tsp (eat 1500mg - 1600 mg) about 1/2 hour before bed.

1 Like
#417

Still on fertility: The protective effects of melatonin on testis, sperm parameters quality, and in-vitro fertilization in mice following treatment with aflatoxin B1: An experimental study 2025

These findings demonstrated that MLT can compensate for the adverse effects of AFB1 on the quality of testicular tissue, sperm parameters, sperm DNA, and in vitro fertilization outcomes.