Life Extension Magazine®

Doctor examining holographic brain after supplementing with DHEA

DHEA Protects the Aging Mind

Normal aging results in shrinkage of brain volume. DHEA can increase the number of brain cells, while combating factors that contribute to cognitive decline and mood disorders.

Scientifically reviewed by: Dr. Gary Gonzalez, MD, in August 2023. Written by: Alexis Sandrio.

New studies are pointing to a novel way of protecting the aging mind: supplementation with DHEA.

In animal models, DHEA has the remarkable ability to increase the number of brain cells, while combating specific features of metabolic syndrome that contribute to cognitive decline.

Human studies show that supplementation with DHEA has dramatic impacts on mood disorders—especially depression—and can improve memory and cognition in older adults.

DHEA also helps combat conditions that contribute to brain aging such as diabetes and vascular disease.

DHEA and the Brain

DHEA and the Brain  

DHEA (dehydroepiandrosterone) is the most abundant steroid hormone in humans, and has biological effects throughout the body.1,2

DHEA has its own receptors on many cells including cells in the brain.2

As people age, adrenal gland secretion of DHEA markedly declines.

Epidemiological studies link lower levels of DHEA with degenerative illnesses including cardiovascular, metabolic, and neurological disorders.2

Because DHEA acts so powerfully on the brain, it is hardly surprising to find that it is intimately associated with a variety of brain-health issues. Studies show, for example, that people with higher DHEA levels have less mental confusion, lower anxiety, and a less negative mood.3

Other studies have found that DHEA levels (in its circulating, sulfated form, DHEA-S) correlate with overall cognitive function in men and women, and with better working memory, attention, and verbal fluency found in women with the highest levels.4

DHEA also plays a significant role in mental illness—especially depression. A recent study found that among people with major depression, those with higher DHEA levels were more likely to experience remission of their symptoms when treated with antidepressants, suggesting that such drugs may require a particular level of DHEA to be most effective.1

Low DHEA levels are also correlated with brain shrinkage in major depression. One 2016 study showed that high cortisol/low DHEA ratios are associated with smaller volume of the hippocampus (the main memory-processing region of the brain) in people with major depression.5 This could contribute to some of the memory and decision-making problems often experienced by people with depression.

Indeed, low DHEA levels are now associated with multiple brain-related disorders, including stress-induced clinical burnout, bipolar disorder, major depression, anxiety, and chronic fatigue syndrome.6-15

Fortunately, DHEA supplements cost only pennies a day, and numerous studies show that supplementation can directly oppose loss of brain function.

Memory and Cognition

Memory and Cognition  

Postmenopausal women taking 50 mg/day of DHEA can boost memory recognition tasks and enhance a variety of cognitive skills—especially those relating to perception and judgment.16,17

In a study of older women with mild-to-moderate cognitive impairment (a likely precursor to Alzheimer’s), taking 25 mg/day of DHEA increased cognitive scores and prevented loss of skills needed for activities of daily living, while also improving verbal test scores.18

Larger doses appear to have more potent effects. Among healthy young men, 300 mg/day of DHEA for seven days improved mood and memory, lowered evening cortisol levels, and caused changes in nerve impulses in memory-related brain regions.19 (This dose is experimental and not recommended for routine supplementation.)

In a follow-up study, healthy young men who took a single dose of 400 mg of DHEA experienced activity changes in the brain that were associated with a reduction in negative emotions (sadness, anger, etc.), as well as reduced memory of emotionally-disturbing events, when compared to patients taking a placebo.20 (Doses to replenish DHEA to physiological youthful levels typically require only 15 mg to 25 mg a day.)

A specialized MRI scan revealed that DHEA reduced activity in the aggression-dominated amygdala region of the brain and increased connectivity between the amygdala and the hippocampus. These are changes that would be expected to produce less emotionally reactive and more positive rational thoughts.20

Interestingly, the other common stress-induced steroid hormone, cortisol, has directly opposite effects, contributing, when high, to depression and anxiety.3 This makes DHEA an appealing counterbalance to stress-induced cortisol elevations. Studies confirm that those with higher ratios of cortisol-to-DHEA have more anxiety, general mood disturbances, greater confusion, and lower memory performance on visual-spatial tasks.3

Mood Disorders

Studies show that DHEA supplementation may be a promising addition to—or even replacement for—some of today’s powerful psychoactive drugs.

In one study, schizophrenic patients taking 200 mg/day of DHEA for six weeks had improvements in sustained attention, visual, and movement skills—all of which help to mitigate some of the impact of the disease.21

But it is in the treatment and prevention of mood disorders (commonly including depression and anxiety) that DHEA is showing the most dramatic mental health promise.

In one study, subjects with midlife dysthymia (a mild but chronic form of depression) took 90 mg of DHEA daily for three weeks and then 450 mg daily for another three weeks, or placebo for six weeks.11 A significant treatment response was detectable after the first three weeks. After six weeks, 60% of people supplementing with DHEA experienced more than a 50% reduction in symptoms, compared with just 20% of placebo recipients.11

In another study, middle-aged and elderly patients with major depression and low plasma DHEA levels received 30-90 mg/day of DHEA, with the dose adjusted to raise plasma levels to those of healthy young people.15 After four weeks, depression ratings and memory performance improved significantly in proportion to rising DHEA levels.

The findings of DHEA’s potent antidepressant action have now been replicated in many individual studies using daily doses of 25 mg or more. These improvements are often accompanied by additional benefits such as memory and libido enhancements.8-10,12,14

What You Need to Know
DHEA Protects Brain Health

DHEA Protects Brain Health

  • Levels of the abundant steroid hormone DHEA fall with advancing age.
  • Studies now show that insufficient DHEA is a risk factor for declining cognitive and memory function, as well as mood disorders including depression and anxiety.
  • Supplemental DHEA is a proven means of combating those neurological conditions.
  • DHEA also mitigates conditions that contribute to cognitive decline, such as metabolic syndrome and its consequences, including diabetes and cardiovascular disease.
  • In combination, DHEA’s direct effects on the brain, as well as its indirect effects through reduction in cardiometabolic dysfunctions, make it an ideal supplement for sustaining a healthy mind in a healthy body.

How it Works

Animal studies are shedding some light on the specific mechanisms involved in DHEA’s beneficial effects on cognition, memory, and mood.

One study showed that DHEA switched on expression of steroid-responsive genes in close correlation with cognitive performance, which suggests that DHEA operates at least in part by modulating gene expression in brain cells.22

A 2017 study showed that DHEA treatment in middle-aged rats undergoing chronic mild stress (a cause of cognitive and memory problems) increased the number of specific brain cells, while also enhancing maturation of the multiple branching projections of those cells (dendrites).23 Boosting these connections help brain cells sustain normal cognition and memory in the face of connections lost to aging and disease.

But other factors are likely at work in DHEA-induced brain protection. Two of the most important are its impact on metabolic disorders (diabetes, obesity) and cardiovascular diseases (atherosclerosis, endothelial dysfunction), since these areas have known consequences in the brain.

Let’s examine these connections.

DHEA Combats Metabolic Disorders

DHEA Combats Metabolic Disorders  

Metabolic syndrome (the combination of obesity, hypertension, elevated blood sugar, excess body fat around the waist, and abnormal cholesterol or triglycerides levels) raises the risk of cognitive dysfunction over time.24 High blood sugar and insulin levels play major roles. DHEA is emerging as an important factor in governing those metabolic parameters.

Studies show that middle-aged and elderly people with higher DHEA levels are at about 20% lower risk for new-onset diabetes compared with those with lower DHEA levels—with that protection rate as great as 77% among men.25,26 The reason for this protective effect is clear: DHEA has a remarkable impact on body fat and blood sugar. In men with metabolic syndrome, supplementation with just 25 mg/day of DHEA lowered blood sugar by 26%.27

One study found that DHEA is as effective in reducing body fat and maintaining insulin sensitivity as exercise!28 Specifically, older rats supplemented with DHEA gained 11% less weight than control animals, reflecting a 25% reduction in body fat with minimal impact on muscle mass. They also cleared glucose from their blood 30% more effectively than control animals.28 (Human studies do not show as dramatic an effect on body fat mass.29)

Together, these findings suggest that DHEA-mediated blood glucose and insulin reductions could provide protection against neurodegenerative diseases like Alzheimer’s, which has sometimes been called “type III diabetes” because of its close association with uncontrolled glucose levels.30,31

DHEA Protects Arteries

Diabetes isn’t the only consequence of our typical high-fat, high-sugar Western diet. It also causes a significant amount of blood-vessel damage. In addition to setting us up for heart disease, strokes, and other cardiovascular disasters, this type of damage paves the way for diminished neurological and cognitive function. DHEA is showing promise in protecting the arteries against some of those destructive effects.

In men with elevated cholesterol, taking 25 mg of DHEA daily for 12 weeks produced an impressive 115% improvement in endothelial function, a measure of arterial health and resistance to atherosclerosis.27 That study also showed a significant 44% reduction in plasminogen activator inhibitor, which is a measure of blood-clotting potential. This important finding indicates an independent reduction in cardiovascular risk.27

DHEA supplementation in elderly males also increases the ability of platelets to produce artery-dilating nitric oxide (NO) and lowers LDL cholesterol levels.32

Animal studies offer additional insights. For example, diabetic rats supplemented with DHEA showed significant improvement in their ability to dilate (widen) their arteries, particularly the tiny arterioles that feed nerve cells. This reduces the potential for diabetic vascular and neurological disorders.33

In rabbits fed a high-fat diet, DHEA supplementation reduced or reversed the pro-inflammatory state induced by fat tissue, while lowering blood lipid levels and, ultimately, delaying the onset of heart-muscle damage.34

Finally, DHEA shows promise for protecting against nonalcoholic fatty liver disease (NAFLD), a manifestation of metabolic syndrome and an early risk factor for chronic liver disease.35

Collectively, these findings demonstrate that DHEA combats metabolic syndrome by reducing weight gain, lowering blood lipids, improving vascular function, reversing inflammatory changes, and preventing fat-induced liver damage.

All of these properties show just how powerfully DHEA reduces the risk of neurological disorders related to vascular dysfunctions.



DHEA has powerful brain-preserving properties. Levels of DHEA fall with advancing age, which leaves brain tissue and structures increasingly vulnerable to metabolic, toxic, and chemical threats. It may also contribute to problems ranging from mild cognitive impairment to neurodegenerative diseases, as well as mood and other mental health disorders.

Supplementation with DHEA has been shown to help prevent or mitigate mood disorders, especially major depression, and to significantly improve cognitive and memory functions in older adults.

DHEA also combats the metabolic and vascular disorders that can promote brain dysfunction with age. Studies show that DHEA can reduce blood sugar, raise insulin sensitivity, reduce weight gain, lower cholesterol levels, and improve blood-vessel functioning—all of which lower one’s risk for metabolic syndrome and its consequences, heart disease, diabetes, and neurological damage.

For those interested in optimizing their nutritional and hormonal balances to fight the ravages of aging, DHEA represents an ideal multitargeted supplement with known safety and a growing number of anti-aging properties.

If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.


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