HPA Axis Commentary Part 2


Corey Schuler, MS, DC, CNS, LN, FAAIM? is a nationally recognized expert in the field of natural health and metabolism. He is a board-certified physician with the certification board of nutrition specialists, licensed nutritionist, and functional medicine practitioner with a profound curiosity about why one medicine heals one person with a condition but not another with the very same condition. He is a member of the American College of Nutrition and American Nutrition Association, holds a master’s degree in human nutrition, and teaches in post-graduate degree (MS, MSACN, MHS) programs of clinical nutrition.


Integrative Medicine: A Clinician?s Journal (IMCJ):?When you think of a condition like chronic inflammation, for instance, is it a chicken-or-the-egg situation, where the chronic inflammation impacts the stress, or does the stress impact the body to create the chronic inflammation?

Dr Schuler: It will absolutely go both ways. The hypothalamus secretes something called CRH? corticotropin-releasing hormone?or corticotropin-releasing factor, CRF, depending on whom you read. That circulates because of stress. It?s actually the signal that tells the pituitary to release adrenocorticotropic hormone, or ACTH. And ACTH is the signal that tells the adrenal glands to release cortisol. You can see where it fits. It?s way high up on the physiologic cascade. When that CRH or CRF circulates, it actually increases intestinal permeability, and so it can lead to things like intact proteins crossing into the blood stream, causing autoimmune-type reactions or allergy-type reactions. That?s, of course, very problematic.

We have also seen things like micronutrient malnutrition. Just removing 1 or 2 nutrients from an individual?s diet, and controlling for that, will strike up all the same stress responses. Any stress, even things like just not getting enough nutrients, can signal that entire cascade. Just like waiting in line at the bank: ?I didn?t get enough B6.? It?s the same cascade that happens.

IMCJ: How does the lack of sleep impact that?

Dr Schuler: The lack of sleep is a really interesting one. The lack of sleep, inflammation, and HPA activation are all very intimately tied together. We have not quite figured that one out. The simple answer is that lack of sleep increases inflammation, and increased inflammation, impacts sleep. It actually causes daytime sleepiness and causes people to not be able to fall asleep at night. The HPA activation causes lack of sleep, and lack of sleep causes increased HPA activation. HPA activation causes poor sleep habits, as well, such as not winding down at night and trouble falling asleep. It is actually the same type of response.

IMCJ: Then throw in the other conditions related to poor sleep, and hypertension would be the result.

Dr Schuler: Hypertension could be the result, so the endothelial tissue is sort of one of the target organs for all of these downstream effects. They called hypertension the silent killer, before they called inflammation the silent killer. Well, it?s intertwined together. It makes sense.

IMCJ: We know what all the issues are, so what is a solution? For instance, you can certainly take pharmaceuticals for hypertension, but they do not necessarily cure the hypertension. They just lower your blood pressure.

Dr Schuler: Correct. Sometimes, they do not work all that effectively. The best solution would have to be that we adapt better to the stresses in our environment. It is the easy, simple, but really complex solution to that.

What I will tell patients?and I have been known to say this on various places, podcasts, and radio shows?the very bad news that, ?You?re sick. You?re in a stressful environment. You?re placing additional stress on yourself, so that is a separate and distinct issue, and for the most part, things aren?t going to get better.?

That is not usually the hopeful type of message that you want from an integrative practitioner. What I mean by that, and I do explain it pretty thoroughly, is that life does not get less stressful as you age and mature. There are all these things that are still happening. You just get stressed out by different stuff. The thought of, ?Well, once my mortgage is paid off,? or, ?Once I get a better job,? or, ?Once I meet the right person,? then everything will be better. That is never the case. You have a stress-response set point for the most part, and you respond to stresses similarly, no matter what stressor you are facing.

Again, unless you can fundamentally change that, you are in trouble. The reason that we are talking is because some of the things that are improving that stress response are things like adaptogenic botanicals, or nutrients that are geared toward the HPA axis, and some of the nutrients that reduce that negative consequence or collateral damage of HPA chronic activation.

IMCJ: Is there a way to measure a person?s stress level?

Dr Schuler: As an intermediate marker, so it is not an endpoint, we like to look at cortisol levels. Conventionally, we look at blood tests in the morning for cortisol, which is okay, but unfortunately that is only looking at the endpoints. We look at it if you are way high or way low. If you?re way high, you end up with a diagnosis of Cushing?s disease. If you?re way low, you end up with a diagnosis of Addison?s disease, probably. The body tries to maintain homeostasis so there are fluctuations before adrenal disease is diagnosed.

We had to look for other markers. We have been working with salivary cortisol for 30 or 35 years and we have pretty good data on it. We also know that it is not perfect, and we know what the problems are with it. Usually it is a sampling error, rather than a laboratory error. What I mean by that is: People take their sample too early. You really have to wait 30 to 45 minutes after waking to take your first salivary cortisol sample. Quite often, people goof that up, either on the short side, or they wait too long. They miss this really important spike in cortisol that is normal and supposed to happen 30 to 45 minutes after waking. They call it the cortisol awakening response, or CAR.

Recently, we have been really interested in what they call urinary testing of cortisol. We have tested cortisol, usually? over the period of 24 hours. We measure how much cortisol you produced in total. That was a really great test, because it told you where you fit in that stress spectrum. What it did not tell us was variation throughout the day. Does that go up and down or not?

Relatively recently, they showed that a first morning urinary void was as good as measuring the 24-hour cortisol in the urine, which is great, because most patients don?t want to carry a big orange jug around with them for a whole day. You have to do the test during a normal, stressful day. You can?t just wait for a weekend, because that is a different stress experience. It was not a very comfortable thing. Companies have come out with the dried urinary testing, or first morning void urinary testing. That, I think, is probably the next thing in measuring stress.

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