In my experience, one of the toughest issues to manage is cortisol dysfunction, i.e., dysregulated release of this stress hormone. Dysfunction can take on a number of different patterns: disorders of timing, disorders involve excessively high or excessively low quantities. The experience can vary significantly from individual to individual.

Cortisol release by the adrenal gland is the end-result of activation of the so-called hypothalamic-pituitary axis. When confronted with any form of stress, the hypothalamus is triggered to release corticotropin-releasing hormone, CRH, that, in turn, triggers release of adrenocorticotropic hormone, ACTH, from the pituitary gland that provokes release of cortisol by the adrenal gland.

The most common health situation is when someone is exposed to a chronic stress, i.e., repeated exposure to verbal abuse, being devalued, financial stress, meeting the demands of a child or parent whose care you provide, maternal deprivation in a child, and others. Interestingly, increased blood levels of the lipopolysaccharide (LPS) endotoxin, as occurs in colonic dysbiosis and especially in small intestinal bacterial overgrowth, SIBO, has also been shown to lead to HPA activation and excessive cortisol release. Regardless of cause, exposure to prolonged stress can be manifested in a number of ways that include chronic fatigue, sleeplessness, early morning awakenings (e.g., awakening at 3 a.m. with difficulty falling back asleep), inappropriate surge in wakefulness late at night. These phenomena can take a physical toll, as the potential for hippocampal atrophy that leads to cognitive impairment and dementia can result, as well as an increase in abdominal visceral fat, increased inflammatory phenomena, increased insulin resistance. In short, stress, with effects exerted via the HPA axis, can have major effects on health over time.

Cortisol status is most commonly assessed with a 4-sample salivary cortisol profile, such as that shown below:

From ZRT Labs

Saliva samples are usually collected (in a tube) upon awakening, 30-45 minutes later (that usually captures the peak), noon, dinnertime, then bedtime. Among the most common dysfunctional patterns seen are:

  • Excessive high morning surge with higher levels during the rest of the day, experienced as feeling excessively stressed all the time
  • Low levels of the morning surge and lower levels during the rest of the day, experienced as chronic fatigue
  • An inappropriate mistiming of a surge around bedtime that makes falling asleep difficult
  • An inappropriate surge in the middle of the night, i.e., early morning awakening, that prevents you from falling back asleep

The functional medicine and integrative health communities have advocated a variety of solutions for such patterns, solutions that include phosphatidylserine, various “adaptogens” (an awful term, in my view) such as ashwagandha or rhodiola, melatonin, and oral hydrocortisone to boost low levels. Unfortunately, aside from hydrocortisone, I have never seen any of these strategies work. They don’t suppress excessively high levels nor do they correct circadian mistiming.

Low cortisol levels, both a.m. surge and during the day, is often labeled “adrenal fatigue.” But this is misleading, as a “burned out” adrenal gland is not to blame (and has been the perennial focus of critics of this situation). Instead, there are complex epigenetic changes that occur, i.e., changes in the proteins that regulate gene expression involving CRH and ACTH that are very difficult, perhaps impossible given current knowledge, to undo. If we do not yet know how to reverse these adverse epigenetic changes, what can we do to deal with the various forms of suspected cortisol dysregulation?

The gastrointestinal (GI) microbiome is beginning to yield some interesting possibilities, another example of the gut-brain axis mediated, at least in part, through the vagus nerve. Recent observations include:

  • L. reuteri ATCC PTA 6475–in experimental animals, a dramatic reduction (50%) in cortisol levels was observed.
  • L. gasseri CP2305–10 billion heat-killed microbes per day reduced stress-induced cortisol surges in human participants.
  • Lactobacillus casei Shirota–100 billion CFUs per day reduced salivary cortisol levels during stress. (Ferment from the Yakult product.)
  • Lactobacillus helveticus R0052 and Bifidobacterium longum R0175–3 billion CFUs per day modestly reduced urinary cortisol. (Available as the Innovix Mood product. However, I am somewhat skeptical about the effects of this combination that has yielded uneven results in real world experiences.)

Cortisol-reducing effects appear to be shared by numerous species of Lactobacillus. Others besides the ones listed above are likely to emerge in future. And, given the association of LPS endotoxemia and activation of the HPA axis that causes higher levels of cortisol to be released, addressing SIBO is a very good idea to reduce cortisol levels, also.