Higher levels of DHEA may enable you to …

Make Better Everyday Decisions
And thereby enhance your quality of life

By Will Block

Iehydroepiandrosterone (DHEA) exists in the human body in sulfate form (DHEA-S), where it operates as an important anabolic protective hormone for health maintenance and promotion. DHEA-S (hereafter DHEA) levels peak in young adults and decline thereafter with age. For this and other reasons, DHEA is frequently referred to as the youth hormone (see Fig. 1).

Meeting Criteria for Most Effective Life Extension Nutrients

Life Enhancement’s Medical Editor Dr. Ward Dean has long been a prolific thinker and writer about antiaging/life extension topics. In fact, he is the author or coauthor of five influential books and consequently an originator of numerous insights and conclusions that dwarf those of many so-called experts throughout the entire field.1

Dr. Dean writes, “There is, of course, no ‘silver bullet’ for the aging process. There is no single substance that has been proved to retard the human aging process. The studies have just not been done. Nevertheless, I don’t recommend doing nothing while waiting for someone to perform the studies to provide the definitive answers. (Emphasis added.)

The More Aging Mechanisms Acted on the Better

“I’ve selected the substances to be discussed based on several criteria: First, I considered the mechanism by which the substance is believed to act. Most substances that will be discussed in this series act by multiple mechanisms. I place special importance on the mechanisms, which are involved in one or more theories of aging (i.e., antioxidants/free radical theory; cross linkage inhibitors/cross linkage theory; hormone receptor sensitizers/neuroendocrine theory, etc.). (Emphasis added.)

Reversing or Restoring Age-Related Biomarkers

Figure 1. Decline of DHEA-S with age. See Orentreich N, Brind JL, Rizer RL, Vogelman VH. Age changes and sex differences in serum dehydroepiandrosterone sulfate concentrations throughout adulthood. J Clin Endocrinol Metab. 1984 Sep;59(3):551-5.
LEM1403pylori_graph274.gif

“Second, I considered the health-enhancing effect of the substance. Third, of great importance, was whether the substance has shown the capability to reverse or restore a biomarker to a more youthful state. And fourth, and most important, has the substance demonstrated the ability to extend the maximum lifespan of one or more experimental organisms? (Emphases added.)

Pill Capacity, Cost and Availability, and Legal Issues

“I include practical considerations, as well. Among these are an individual’s ‘pill capacity’—how many capsules/tablets is a person willing to take? Also, we must consider the cost and availability—for example, some substances are beyond the reach of many people due to high cost or other impediments (i.e., legal issues, availability, requirement for a prescription, etc.).” (Emphases added.)

DHEA—Among the Most Effective Anti-Aging/Life Extending Substances Readily Available Today

Among Dr. Dean’s major points about DHEA:

Figure 2. Steroid hormone cascade, illustrating the central position of DHEA. In addition to having significant properties of its own, DHEA acts as a “hormonal buffer,” converting to other hormones as needed.
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(click on thumbnail for full sized image)

DHEA is the most abundant steroid hormone in the body—has been thought of as “the mother steroid,” due to its key position in the steroid hormone cascade2 (Fig. 2.)

DHEA reaches its highest levels in the blood at age 20-24, and drops progressively with age thereafter. This decline is so momentous (the level of DHEA in 70-year-olds is only about 20 percent that of young adults) that it has been referred to as the “DHEA Deficiency Syndrome—a new term for old age.”3

DHEA is “the most significant endocrine biomarker”4 (Fig. 2). Ironically, for many years, scientists believed that DHEA was merely a metabolite, with no physiological effects of its own. However, continuing research over the years repeatedly confirms that this is not the case.

DHEA has previously been shown to be lower in individuals reporting prolonged stress. According to a recent investigational study, DHEA levels are low in patients with clinical burnout, a disorder caused by long-term psychosocial stress. (See “Low DHEA Levels Linked to Burnout” in the November 2015 issue).

Stress and Decision Making

Not much is known about how acute stress influences the ability to make better decisions in everyday life. But stress can affect performance for many cognitive abilities. In a new paper conducted at the University of California, Davis,5 researchers addressed that gap in a study by using a gold-standard laboratory manipulation of acute stress and subsequently-assessed decision-making competence in stress and control groups while also collecting saliva samples to assay stress-reactive hormones with cognitive effects.

Better Real-World Decisions and Stress

The researchers found—perhaps counter-intuitively—that acute stress actually enhanced the ability to make better real-world decisions—“decision-making competence.” Moreover, they showed that although stress-induced increases in both cortisol and DHEA predicted decision-making competence, DHEA evidenced a significantly stronger association when both hormones were considered simultaneously.

To add strength of these associations there was a lack of interactions with age, sex, and other variables. For the first time, the study reveals that acute stress can exert beneficial effects on the decision-making ability that appears to support better decision-making in everyday life.

Stress Enhances Decision-Making Competence

The study’s findings support the hypothesis that acute stress enhances decision-making competence. Further, these findings also provide empirical support for one pathway by which acute stress may influence decision-making.

In particular, after accounting for the covariance between cortisol and DHEA, only post-stressor DHEA predicted decision-making competence.

Moreover, Bayesian parameter estimation (Bayesian refers to methods in probability and statistics, in particular methods related to statistical inference:) confirmed that post-stressor DHEA was a significantly better predictor of decision-making competence than post-stressor cortisol. It is also worth noting that potential confounders such as subjective experience of stress did not play a role in producing a stronger association between DHEA and decision-making competence than cortisol. That is, the effect of stress relative to the control condition on cortisol reactivity was greater than that effect on DHEA reactivity.

Thus, the data strongly suggest that DHEA is a better predictor of stress-induced alterations in decision-making competence than is cortisol.

At a neurobiological level, some of DHEA’s actions result in increased dopaminergic activity in the prefrontal cortex. Increased dopaminergic activity can both enhance cognitive functions and alter decision-making.

Alterations in Dopaminergic Activity

Thus, the UC Davis results add to a growing list of stress effects due to alterations in dopaminergic activity. It should be noted that DHEA is also a neurosteroid that is present within brain regions supportive of decision-making function. Additionally, most DHEA is converted to its sulfate ester—DHEAS—and DHEA-S can exert neurobiological effects of its own.

Given the common experience of making a regrettable decision while stressed, how is it that stress can enhance decision-making competence?

One possible answer may lie in how stress influences emotions and reward salience. In particular, stress can make rewarding stimuli more appetizing, and it increases the intensity of negative distress.

As such, while stressed, one might be more tempted to indulge in a pleasurable activity one later regrets or be more tempted to make poor decisions based upon one’s current mood. This explanation also fits with the fact that most of our poor decisions made during stress were made even when we “knew better”—or, had the decision-making competence to know that it was a bad decision. Thus, although stress enhances decision-making competence, benefits of this enhanced decision-making capability might not always be readily apparent. Future research should attempt to determine if this is indeed the case.

Because decision-making competence plays such an important role in everyday life, the potential for enhancing it has important implications. For example, because greater decision-making competence predicts better decision-making in interpersonal and financial situations, greater decision-making competence is associated with a more positive social environment and higher socioeconomic status, though it should be noted that many factors contribute to these circumstances.

In addition, people with greater decision-making competence are more likely to hold high-level leadership positions.6 As such, improving decision-making competence could potentially enhance a person’s interpersonal quality of life and, once again, socioeconomic status.

It follows that understanding the biological mechanisms underpinning the effects of stress on decision-making competence could provide enormous societal benefits. Future research should thus attempt to determine if experimentally manipulating DHEA using a pharmacological approach enhances decision-making competence. There is plausible evidence for this already.

DHEA May Enhance Cognition and Decision Making

In several studies, DHEA supplementation has been found to enhance cognitive function,7,8,9 and more importantly to the UC Davis paper, DHEA administration may enhance decision-making. Individuals who were administered DHEA during rehabilitation from drug addiction were significantly less likely to choose to use drugs during the time they were given DHEA and their levels of DHEA-S were higher, than were individuals given a placebo.10

In this double blind, placebo-controlled study, researchers examined the effect of DHEA on relapse rates among adult polydrug users. During treatment, participants (79 percent males, mean age 28) consumed DHEA (100 mg/day) or placebo daily for at least 30 days. DHEA reduced negative affect on the Positive and Negative Affect Scale. Furthermore, in a 16-month follow-up, the researchers found that re-use rates in the DHEA condition were about a third compared with placebo. DHEA treatment also resulted in an increase in DHEA sulfate (DHEA-S) 1 month following treatment, and the level of DHEA-S predicted relapse in the follow-up assessment.

Although it is unclear whether this choice is due to enhanced decision-making competence, decision-making competence is a strong, inverse predictor of poor decisions regarding use and abuse of intoxicating substances, lending credence to the idea that administration of DHEA enhances decision-making competence.

Thus, in the UC Davis study, given the associations between DHEA, cortisol, and decision-making competence, a factorial manipulation of DHEA and cortisol could provide important insight into how stress enhances decision-making competence and potentially elucidate a mechanism through which to enhance decision-making competence.

Several strengths of the UC Davis study are notable. First, their use of gold-standard methodology ensures that they have accurately manipulated and assessed what was intended. Second, the excellent coefficients of variation, coupled with the consistency of all of their control values within expected ranges, provides confidence that the hormone effects observed are genuine and robust. Third, the large sample size ensured that this study evidenced sufficient power to detect a true effect and made it unlikely that sampling error produced the effects observed here—as can happen with smaller sample sizes.

Finally, the use of advanced statistical techniques, such as Bayesian parameter estimation, allowed for a rich analysis of the observed data and provided security against potential violations of assumptions related to models used in null hypothesis significance testing.

In conclusion, in a large sample of healthy young adults, the UC Davis scientists found that exposure to acute stress enhanced the decision-making ability that appears to underpin better decision-making in everyday life—decision-making competence.

Moreover, the researchers provided correlational support for the idea that DHEA may have contributed to this effect, because although stress increased both DHEA and cortisol, stress-induced increases in DHEA were a significantly better predictor of decision-making competence than cortisol.

The scientists concede that the correlational nature of their results cannot establish causation, and suggest that a factorial manipulation of DHEA and cortisol should be a fruitful avenue for future research, especially considering the important implications of enhancing decision-making competence. However, as Dr. Dean has written with regard to DHEA (see above), “I don’t recommend doing nothing while waiting for someone to perform the studies to provide the definitive answers.”

References

  1. Dean W. Anti-Aging Nutrient Review and Update. http://warddeanmd.com/dhea-begins-new-series/ 2015. Accessed: May 30, 2016
  2. Regelson W, Loria R, Kalami M. Dehydroepiandrosterone (DHEA)—the “Mother Steroid.” I. Immunologic action. Ann NY Acad Sci. 1994 May 31;719:553–63.
  3. Hinson JP, Raven PW. DHEA deficiency syndrome: a new term for old age? J Endocrinol. 1999 Oct;163(1):1-5.
  4. Regelson W, Kalimi M, Loria R. Deheydroepiandrosterone (DHEA): The precursor steroid, in: The Biologic Role of Dehydroepiandrosterone (DHEA). Eds. Regelson W, Kalimi M. New York: Walter de Gruyter; 1990.
  5. Shields GS, Lam JC, Trainor BC, Yonelinas AP. Exposure to acute stress enhances decision-making competence: Evidence for the role of DHEA. Psychoneuroendocrinology. 2016 May;67:51-60.
  6. Carnevale JJ, Inbar Y, Lerner JS. Individual differences in need for cognition and decision-making competence among leaders. Pers Individ Dif. 2010;51(3): 274-8.
  7. Morgan CA 3rd, Southwick S, Hazlett G, Rasmusson A, Hoyt G, Zimolo Z, Charney D. Relationships among plasma dehydroepiandrosterone sulfate and cortisol levels, symptoms of dissociation, and objective performance in humans exposed to acute stress. Arch Gen Psychiatry. 2004 Aug;61(8):819-25.
  8. Morgan CA 3rd, Rasmusson A, Pietrzak RH, Coric V, Southwick SM. Relationships among plasma dehydroepiandrosterone and dehydroepiandrosterone sulfate, cortisol, symptoms of dissociation, and objective performance in humans exposed to underwater navigation stress. Biol Psychiatry. 2009 Aug 15;66(4):334-40.
  9. Rasmusson AM, Vasek J, Lipschitz DS, Vojvoda D, Mustone ME, Shi Q, Gudmundsen G, Morgan CA, Wolfe J, Charney DS. An increased capacity for adrenal DHEA release is associated with decreased avoidance and negative mood symptoms in women with PTSD. Neuropsychopharmacology. 2004 Aug;29(8):1546-57.
  10. Ohana D, Maayan R, Delayahu Y, Roska P, Ponizovsky AM, Weizman A, Yadid G, Yechiam E. Effect of dehydroepiandrosterone add-on therapy on mood, decision making and subsequent relapse of polydrug users. Addict Biol. 2015 Mar 26. doi:10.1111/adb.12241.


Will Block is the publisher and editorial director of Life Enhancement magazine.

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