Life Extension Magazine September 2013
Melatonin: The Brain Hormone
By Stephen Fredericks
Melatonin Fights Parkinson’s at the Earliest Stages
Animal studies demonstrate that melatonin supplementation can prevent—and to some extent, even reverse—the changes in behavior and motor function induced by Parkinson’s disease.33-35 Parkinson’s disease robs its victims of normal movement, slowing them down, making their walk erratic, and blocking normal facial expressions.35 All of this occurs through the loss of neurons that produce the neurotransmitter dopamine. 33
Parkinson’s has a number of similarities to Alzheimer’s. Both can lead to dementia. Both are the result of out-of-control oxidation (in the case of Parkinson’s focused on brain regions that control movement and balance).20,35 And in both diseases, brain cell death and dysfunction is brought on by an abnormal, oxidizing, and inflammatory protein accumulation. In Parkinson’s, that protein is called alpha-synuclein. 36,37
Working with various laboratory models of Parkinson’s disease, scientists have demonstrated that melatonin can attack Parkinson’s disease at each of its critical junctures:
- It prevents the production of alpha-synuclein in brain cells, at the same time attacking existing molecules of the toxic protein and making them available for cellular cleanup.36,37
- It reverses the inflammatory changes seen in the brains of people with Parkinson’s disease.38
- It restores normal activity of a key enzyme involved in dopamine production.8,24
Melatonin’s ability to prevent—and reverse—the changes in behavior and motor function induced by the disease is the result of enhanced survival of the dopamine-producing cells that become damaged or destroyed in Parkinson’s disease.8-10
Melatonin Cuts Stroke Risk
As you age, waning melatonin levels place your brain at risk for both immediate and long-term neurological damage. In particular, decreased melatonin levels have been associated with a greater presence of stroke, with the odds appearing to rise more than 2% for each 1 pg/mL decline in melatonin.39 In people whose pineal gland (the source of melatonin) has become calcified and non-functional, the risk of stroke is increased by 35%.40
Plenty of biochemical evidence is available to explain this increased risk. Much of the damage done in either type of stroke—ischemic (insufficient blood flow) or hemorrhagic (bleeding into the brain)—is the result of free radical production. In an animal model of ischemic stroke, melatonin improved cognition by scavenging and neutralizing free radicals.41
It also reduces indirect risk factors for stroke, such as elevated cholesterol and blood pressure. It has been shown to suppress cholesterol formation by 38%, reduce LDL-cholesterol accumulation by 42%, and reduce blood pressure into the normal range. 42
Melatonin Limits Stroke Damage
Once a stroke has begun to develop, melatonin can prevent the death of neurons in the stroke area—limiting the damage done by the stroke.11 Researchers conducted an experiment in which they removed the pineal glands of rats to make them deficient in melatonin. They found that these rats experienced significantly greater brain damage after a stroke or seizure than the rats that still had sufficient melatonin levels.43
Repeated animal studies have demonstrated that animals supplemented with melatonin prior to a stroke experienced a decrease in the volume of brain tissue affected by an ischemic stroke (the most common kind).11,44-47 This results in improved neurological and behavioral outcomes, and faster recovery from the stroke.11,47,48
One of the most important determinants of a good recovery from a stroke is the degree of “plasticity” in the surviving neurons.49 Plasticity involves how well the surviving neurons are able to shift their function and take on some of the activities of damaged or destroyed brain cells. 49 Melatonin has been found to increase the plasticity of the neurons on both sides of the brain (the affected side and the opposite side)—an effect that hastens recovery.50
Another way melatonin helps reduce the damage caused by a stroke is by reducing the activation of destructive “protein-melting” enzymes.47,51 An ischemic stroke triggers an increase in “protein-melting” enzymes, which impair the integrity of the normal blood-brain barrier, leading to brain swelling, increased pressure, and occasionally transformation into a hemorrhagic (bleeding) stroke.52 However, in experimental models of ischemic stroke, when melatonin is administered during or after ischemia, it reduces the activation of those destructive enzymes, tightens the blood-brain barrier, reduces tissue swelling, and prevents hemorrhagic transformation.11,47,51,53
Melatonin Shields Your Brain from Traumatic Injuries
Melatonin has also been found to help protect your brain in the event of a traumatic brain injury (such as head trauma experienced in an automobile accident). Traumatic brain injury is a leading cause of death and disability in younger Americans (but not unheard of in older adults).54,55
Just as in a stroke, oxidative damage to brain cells is the leading culprit in traumatic brain injuries. Also as in a stroke, promoting brain cell plasticity (the ability of surviving neurons to take on some of the activities of damaged brain cells and to promote re-growth of damaged tissue) is a mainstay of treatment.56
Animal studies show that administration of melatonin after such an injury maintains integrity of the blood-brain barrier, prevents dangerous brain swelling in the hours and days following the injury, and shrinks the size of the bruised and injured tissue.55 It has also been found to reduce the mortality rate after a burst aneurysm.12,13
Most of these effects are related to melatonin’s direct antioxidant effects, along with its ability to induce
otherwise dormant cellular antioxidant systems.13
Can Melatonin Extend Your Life?
There’s no question that melatonin exerts powerful protective effects on brain tissue. We’ve seen how it can mitigate oxidative damage that contributes to neurodegenerative diseases, stroke, and head trauma.
But melatonin is a potent antioxidant that’s also found in the blood, making it accessible to other tissues throughout the body.57 Could melatonin, then, offer true life extension by preventing damage not just to the brain, but to the entire body?
It’s too early to say definitively, of course. Humans live so long that it’s challenging to conduct an ethical, randomized, placebo-controlled study of most interventions. But studies in other animals yield considerable reason for hope.
In the single-celled organism Paramecium tetraurelia, melatonin treatment increased both the mean and the maximal life span by up to 24% over control animals.58 In fruit flies (Drosophila melanogaster), melatonin-fed flies had a 33% increase in maximum life span and a nearly 14% increase in median life span.59
In higher organisms such as mice and rats, data are promising but incomplete. Melatonin increases expression of the “longevity protein” SIRT1, which triggers the expression of a host of self-healing genes (SIRT1 is activated by calorie restriction).14 One study in mice found no increase in mean life span, but an increase in the life span of the last surviving 10% of the population.60 Another study did show increases in longevity in mice engineered to age rapidly.61
Research also shows that animals undergoing calorie restriction—a documented means of extending life span—substantially increase their production of melatonin.19 And melatonin activates (and synergizes with) some of the same brain-protective mechanisms activated by resveratrol, another life-extending supplement.15,62,63