Life Extension Magazine September 2013
Melatonin: The Brain Hormone
By Stephen Fredericks
Melatonin was introduced to the United States in 1992 as a “sleep hormone.”
While some find melatonin helps restore restful sleep, scientists are finding far more consistent applications for melatonin in the area of brain protection.
New discoveries are validating melatonin’s ability to guard the brain from oxidative stress and the neurodegeneration that occurs as a result of aging and environmental factors.1 With this research, melatonin deserves the title of “brain hormone.”
Scientists are increasingly finding that the age-related decline in melatonin levels may be one factor for the age-related increase in neurodegenerative diseases.2-4 In fact, some symptoms of melatonin deficiency are seen in patients with Alzheimer’s, such as disruption of day/night patterns, mood changes, and delirium.5
Fortunately, supplementing with melatonin in middle age and beyond has been shown to protect against Alzheimer’s as well as reduce the risk of Parkinson’s disease, shrink the size of the infarct area involved in a stroke, and minimize the brain swelling and dysfunction following a head injury. 2,6-13
As if this were not enough, research is also finding that in lab studies melatonin can play a role in longevity by increasing the “longevity protein” SIRT1.14,15 Clearly, melatonin’s beneficial properties extend far beyond sleep.
Melatonin’s Role in Neurodegenerative Diseases
Some scientists think the increase in neurodegenerative diseases as we age may be directly related to the age-related decline in melatonin levels.2-4 Fortunately, oral melatonin supplements are available, which may combat this decline by increasing blood and brain levels of melatonin.6,7
Supplementation with low-cost melatonin thus offers an opportunity to restore the brain’s natural antioxidant protection and potentially prevent age-related changes to the brain.2,4,6,16,17 In fact, melatonin’s effects are so powerful that it’s been designated a drug by the European Medicines Agency (EMA).17
With the onset of menopause, animals (like humans) experience a marked increase in oxidative damage, leading to brain cell dysfunction.18 Studies show that in such animals, melatonin supplementation reverses those harmful effects in a similar manner to hormone replacement—but without the associated risks.18
Melatonin Deficiency Linked to Alzheimer’s Disease
Melatonin deficiency and Alzheimer’s disease are closely linked; profound reductions in melatonin levels have been found in Alzheimer’s disease patients. Melatonin, which is maintained at high levels in the brain and spinal fluid throughout youth and middle age, begins to decline sharply with advancing age—in a fashion that closely parallels the rise of Alzheimer’s incidence.2,19,20
One impressive study found that melatonin levels in the spinal fluid of adults older than 80 were just half those of younger, healthy individuals. 21 But older adults who had Alzheimer’s had dramatically lower levels yet—roughly one-fifth of those in healthy young people.
This connection is often overlooked, but vitally important—especially because some of the symptoms that arise as a result of melatonin deficiency are detected long before other more obvious cognitive Alzheimer’s symptoms present themselves.22 This makes melatonin deficiency one of the earliest indicators of Alzheimer’s disease.
Most notably, these include symptoms such as insomnia and sundowning. Sundowning is a “circadian” (daily rhythm) disturbance in which agitation and activity increase, rather than slow down, as the day wanes.23,24 Sleep disorders (such as insomnia, restlessness, and poor sleep quality) generally increase with age and are a sign of declining melatonin production. Such disorders occur in about 45% of those with Alzheimer’s.
Fortunately, clinical research has demonstrated the value of melatonin supplementation in reversing these and other changes associated with Alzheimer’s, particularly when implemented early in the course of the disease.24,25
Melatonin Fights Brain Changes in Alzheimer’s Disease
In animals given the drug haloperidol (Haldol®), which impairs melatonin synthesis, memory deficits and brain protein changes resembling Alzheimer’s disease arise.26,27 However, when the animals are then supplemented with melatonin, the changes disappear, indicating a critical role for melatonin in protecting neurons.
In addition, melatonin has been found to help combat Alzheimer’s disease by reducing the damage caused by two harmful proteins: amyloid beta proteins and tau proteins.6,20,26,28,29 High levels of these two proteins contribute to the death of brain cells and have been linked to Alzheimer’s disease.
Melatonin also helps fight Alzheimer’s disease by guarding against the harmful effects of aluminum, which is known to produce Alzheimer’s-like oxidative changes in brain cells.28
Together, these biochemical effects help to explain why melatonin supplementation has been found to reduce learning and memory deficits in animal models of Alzheimer’s disease.7,30
Why It’s Important to Start Melatonin Early
Researchers agree that it’s best to start taking melatonin before symptoms arise and before physical changes in brain cells have occurred.
One particular animal study demonstrated just how dramatic melatonin’s preventive properties really are. For the study, scientists used mice that had human genes predisposed to Alzheimer’s disease (these are called transgenic mice).7
By late-middle age, the unsupplemented mice proceeded to develop the behavioral and cognitive deficits typical of the disease. In fact, even before signs of disease were visible, the animals’ brains already manifested the typical increased oxidation and decreased intracellular antioxidant defenses seen in Alzheimer’s.7 Soon their brain cells began to die off.
However, mice that were supplemented with melatonin before any disease was evident showed none of those pathological changes—and they performed normally on cognitive and behavioral tests.
This shows just how powerfully melatonin works as a preventive agent. Unfortunately, it’s been difficult to prove these preventive benefits in people because human trials of interventions for Alzheimer’s tend to start only after the disease has become apparent—and well after the window of opportunity for intervention has closed. Nonetheless, very encouraging findings come from studies showing that Alzheimer’s patients taking melatonin experience improved sleep patterns, less sundowning, and slower progression of cognitive impairment.23,24
Still more evidence that it’s best to start melatonin supplements as early as possible comes from several recent studies of mild cognitive impairment, a condition defined as impairment that precedes actual dementia.31 About 12% of people with mild cognitive impairment proceed to develop dementia each year. In a series of studies, researchers have now shown that people taking between 3 and 24 mg of a fast-acting formulation of melatonin daily for 15 to 60 months performed significantly better on a host of cognitive assessment scales and tests of memory.23,31,32