DHEA Protects the Aging MindNovember 2017
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 (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
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
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
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
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.
- Hough CM, Lindqvist D, Epel ES, et al. Higher serum DHEA concentrations before and after SSRI treatment are associated with remission of major depression. Psychoneuroendocrinology. 2017;77:122-30.
- Perrini S, Laviola L, Natalicchio A, et al. Associated hormonal declines in aging: DHEAS. J Endocrinol Invest. 2005;28(3 Suppl):85-93.
- van Niekerk JK, Huppert FA, Herbert J. Salivary cortisol and DHEA: association with measures of cognition and well-being in normal older men, and effects of three months of DHEA supplementation. Psychoneuroendocrinology. 2001;26(6):591-612.
- de Menezes KJ, Peixoto C, Nardi AE, et al. Dehydroepiandrosterone, Its Sulfate and Cognitive Functions. Clin Pract Epidemiol Ment Health. 2016;12:24-37.
- Jin RO, Mason S, Mellon SH, et al. Cortisol/DHEA ratio and hippocampal volume: A pilot study in major depression and healthy controls. Psychoneuroendocrinology. 2016;72:139-46.
- Lennartsson AK, Theorell T, Kushnir MM, et al. Changes in DHEA-s levels during the first year of treatment in patients with clinical burnout are related to health development. Biol Psychol. 2016;120:28-34.
- Lee SY, Wang LJ, Chang CH, et al. Serum DHEA-S concentration correlates with clinical symptoms and neurocognitive function in patients with bipolar II disorder: A case-controlled study. Prog Neuropsychopharmacol Biol Psychiatry. 2017;74:31-5.
- Himmel PB, Seligman TM. A pilot study employing Dehydroepiandrosterone (DHEA) in the treatment of chronic fatigue syndrome. J Clin Rheumatol. 1999;5(2):56-9.
- Ben Dor R, Marx CE, Shampine LJ, et al. DHEA metabolism to the neurosteroid androsterone: a possible mechanism of DHEA’s antidepressant action. Psychopharmacology (Berl). 2015;232(18):3375-83.
- Bloch M, Ish-Shalom S, Greenman Y, et al. Dehydroepiandrosterone treatment effects on weight, bone density, bone metabolism and mood in women suffering from anorexia nervosa-a pilot study. Psychiatry Res. 2012;200(2-3):544-9.
- Bloch M, Schmidt PJ, Danaceau MA, et al. Dehydroepiandrosterone treatment of midlife dysthymia. Biol Psychiatry. 1999;45(12):1533-41.
- Schmidt PJ, Daly RC, Bloch M, et al. Dehydroepiandrosterone monotherapy in midlife-onset major and minor depression. Arch Gen Psychiatry. 2005;62(2):154-62.
- Sripada RK, Welsh RC, Marx CE, et al. The neurosteroids allopregnanolone and dehydroepiandrosterone modulate resting-state amygdala connectivity. Hum Brain Mapp. 2014;35(7):3249-61.
- Wolkowitz OM, Reus VI, Keebler A, et al. Double-blind treatment of major depression with dehydroepiandrosterone. Am J Psychiatry. 1999;156(4):646-9.
- Wolkowitz OM, Reus VI, Roberts E, et al. Dehydroepiandrosterone (DHEA) treatment of depression. Biol Psychiatry. 1997;41(3):311-8.
- Hirshman E, Wells E, Wierman ME, et al. The effect of dehydroepiandrosterone (DHEA) on recognition memory decision processes and discrimination in postmenopausal women. Psychon Bull Rev. 2003;10(1):125-34.
- Stangl B, Hirshman E, Verbalis J. Administration of dehydroepiandrosterone (DHEA) enhances visual-spatial performance in postmenopausal women. Behav Neurosci. 2011;125(5):742-52.
- Yamada S, Akishita M, Fukai S, et al. Effects of dehydroepiandrosterone supplementation on cognitive function and activities of daily living in older women with mild to moderate cognitive impairment. Geriatr Gerontol Int. 2010;10(4):280-7.
- Alhaj HA, Massey AE, McAllister-Williams RH. Effects of DHEA administration on episodic memory, cortisol and mood in healthy young men: a double-blind, placebo-controlled study. Psychopharmacology (Berl). 2006;188(4):541-51.
- Sripada RK, Marx CE, King AP, et al. DHEA enhances emotion regulation neurocircuits and modulates memory for emotional stimuli. Neuropsychopharmacology. 2013;38(9):1798-807.
- Ritsner MS, Gibel A, Ratner Y, et al. Improvement of sustained attention and visual and movement skills, but not clinical symptoms, after dehydroepiandrosterone augmentation in schizophrenia: a randomized, double-blind, placebo-controlled, crossover trial. J Clin Psychopharmacol. 2006;26(5):495-9.
- Sorwell KG, Renner L, Weiss AR, et al. Cognition in aged rhesus monkeys: effect of DHEA and correlation with steroidogenic gene expression. Genes Brain Behav. 2017;16(3):361-8.
- Herrera-Perez JJ, Martinez-Mota L, Jimenez-Rubio G, et al. Dehydroepiandrosterone increases the number and dendrite maturation of doublecortin cells in the dentate gyrus of middle age male Wistar rats exposed to chronic mild stress. Behav Brain Res. 2017;321:137-47.
- Ricci G, Pirillo I, Tomassoni D, et al. Metabolic syndrome, hypertension, and nervous system injury: Epidemiological correlates. Clin Exp Hypertens. 2017;39(1):8-16.
- Veronese N, Trevisan C, De Rui M, et al. Serum Dehydroepiandrosterone Sulfate and Risk for Type 2 Diabetes in Older Men and Women: The Pro.V.A Study. Can J Diabetes. 2016;40(2):158-63.
- Brahimaj A, Muka T, Kavousi M, et al. Serum dehydroepiandrosterone levels are associated with lower risk of type 2 diabetes: the Rotterdam Study. Diabetologia. 2017;60(1):98-106.
- Kawano H, Yasue H, Kitagawa A, et al. Dehydroepiandrosterone supplementation improves endothelial function and insulin sensitivity in men. J Clin Endocrinol Metab. 2003;88(7):3190-5.
- Han DH, Hansen PA, Chen MM, et al. DHEA treatment reduces fat accumulation and protects against insulin resistance in male rats. J Gerontol A Biol Sci Med Sci. 1998;53(1):B19-24.
- Morales AJ, Haubrich RH, Hwang JY, et al. The effect of six months treatment with a 100 mg daily dose of dehydroepiandrosterone (DHEA) on circulating sex steroids, body composition and muscle strength in age-advanced men and women. Clin Endocrinol (Oxf). 1998;49(4):421-32.
- Vieira-Marques C, Arbo BD, Cozer AG, et al. Sex-specific effects of dehydroepiandrosterone (DHEA) on glucose metabolism in the CNS. J Steroid Biochem Mol Biol. 2017;171:1-10.
- Leszek J, Trypka E, Tarasov VV, et al. Type 3 Diabetes Mellitus: A Novel Implication of Alzheimers Disease. Curr Top Med Chem. 2017;17(12):1331-5.
- Martina V, Benso A, Gigliardi VR, et al. Short-term dehydroepiandrosterone treatment increases platelet cGMP production in elderly male subjects. Clin Endocrinol (Oxf). 2006;64(3):260-4.
- Yorek MA, Coppey LJ, Gellett JS, et al. Effect of treatment of diabetic rats with dehydroepiandrosterone on vascular and neural function. Am J Physiol Endocrinol Metab. 2002;283(5):E1067-75.
- Aragno M, Meineri G, Vercellinatto I, et al. Cardiac impairment in rabbits fed a high-fat diet is counteracted by dehydroepiandrosterone supplementation. Life Sci. 2009;85(1-2):77-84.
- Aragno M, Tomasinelli CE, Vercellinatto I, et al. SREBP-1c in nonalcoholic fatty liver disease induced by Western-type high-fat diet plus fructose in rats. Free Radic Biol Med. 2009;47(7):1067-74.