HPA Repair: The Adrenal Reset Diet

Posted June 2, 2015

Alan Christianson, NMD

A PubMed search brings up over 4000 articles from the last 5 years alone that explore the consequences of hypothalamic-pituitary-adrenal (HPA) axis dysfunction. It has been shown¹ to underlie most causes of poor health, disability, and early death, such as:

Alzheimer’s disease
Anxiety
Bipolar disorder
Cancer
Depression
Diabetes
Fatigue
Fibromyalgia
Heart disease
Impaired exercise capacity
Inflammatory bowel disease
Irritable bowel syndrome
Obesity

HPA axis dysfunction (HPAD) is also considered by many obesity researchers to be the prime reason that weight-loss diets are associated with low rates of compliance and low rates of long-term success.^2,3 Even the more recent “food reward theory” holds that HPA dysfunction is the ultimate cause behind the drive toward high-reward foods.⁴

The Adrenals in HPAD

Over the last several decades, alternative medicine has popularized the adrenal role in HPAD, referring to HPAD as adrenal fatigue, adrenal stress, and adrenal dysfunction. Health consumers share this perspective and commonly speak of the consequences of extreme stress in terms of “adrenal burnout” or “crashed adrenals.”

The pathophysiology of HPAD is characterized by abnormalities in glucocorticoid production, circadian cortisol rhythms, peripheral cortisol-cortisone conversion, and tissue glucocorticoid sensitivity.⁵

HPAD, when identified as “adrenal fatigue,” has been suggested to be a mild form of Addison’s disease, which has popularized glucocorticoid replacement therapy as a remedy when a patient presents with low levels of cortisol.^6,7 However, HPAD is distinct from both Addison’s disease and Cushing’s syndrome, due to its lack of adrenal autoimmunity and proportionate cortisol/adrenocorticotrophic hormone (ACTH) levels.⁸ In the case of Addison’s disease, the inverse relationship between ACTH and cortisol is what justifies glucocorticoid replacement. The hypothalamus and pituitary are trying to stimulate the adrenal glands to produce glucocorticoids, but the adrenal glands are unable to do so, due to immune-mediated degeneration of the tissue.

In contrast, in HPAD the adrenals are capable of producing glucocorticoids, but the entire HPA axis is working to reduce this production. This is thought to be an intentional mechanism to limit the body’s energy demands during times of poor stress resilience.⁹ Glucocorticoid replacement therapy may provide some patients a temporary stimulant effect; however, it is working against the intent of the body.

HPAD Treatment

Along with glucocorticoid replacement, the main prescriptive remedies for HPAD have historically been botanical adaptogens and micronutrient cofactors used in adrenal glucocorticoid metabolism.

Adjunctive dietary modifications are often given for HPAD recovery, though these have been more restrictive than prescriptive. Their strategy has been to reduce elements of the modern diet that disrupt the HPA, such as variable meal times, high-glycemic loads, and industrial food ingredients.

Given that the HPA is also used for glucose regulation¹⁰ and that meal-timing is known to correct HPAD,¹¹ I hypothesized that strategic timing of macronutrients may have a prescriptive effect in repairing the HPAD. Since insulin secretion is antagonistic to cortisol,¹² and since glycemic load can alter insulin secretion,¹³ the proposed mechanism is to lower AM glycemic load and to raise PM glycemic load from whole-food sources, to encourage both cortisol awakening response and night-time cortisol reduction.

Studies Using Strategic Timing of Macronutrients

Pilot Study of 1

My first study was a trial conducted on myself (n=1), utilizing continuous glucose meter (CGM) readings and timed measurements of serum cortisol, salivary cortisol, and serum insulin. I observed that a breakfast with over 30 grams of protein and under 10 grams of carbohydrates correlated with higher cortisol levels, and that a dinner with roughly 45 grams of carbohydrates correlated with lower cortisol, compared to a low-carbohydrate dinner.

I used the term “carb-cycling” to describe this process in writings dated from 2011. Since that time, this term has also been used in the bodybuilding community to describe an unrelated process of avoiding carbohydrates for several days, followed by several more days of eating them in high quantities.

Clinical Trial with Patients

After seeing results similar to my own in people with HPAD and dysglycemia, I created a clinical trial to measure the consistency of the response, with Dr Saman Rezaie, NMD, as the study coordinator. Using my social media following, I recruited adults in the Phoenix area who had symptoms of fatigue, insomnia, and resistant weight loss, specifically those who had attempted and failed at least 3 diets within the last 2 years. The group of participants was 80% female, with a median age of 45 years. A total of 48 participants entered the study, and 42 completed the 30-day tracking.

Prior to starting, participants were assessed for HPAD via 4-point salivary cortisol tests; measurements of waist circumference; body weight; body fat, measured via calipers and bio-electrical impedance; and a quiz to quantify HPAD symptom severity, which is available for review at www.adrenalquiz.com.

Participants were placed on an “adrenal reset” diet, consisting of high fiber and carb-cycling (Table 1). Participants were also restricted from possible HPAD disruptors, such as changes in exercise, meditation, or sleep. This way, any measurable changes could be primarily ascribed to the diet.

Table 1. Elements of the Adrenal Reset Study Diet

High Fiber	Possible HPA Disruptors (Remove)	Carb-Cycling Principles
Soluble	Binding proteins (gluten, casein, albumin)	High protein; AM 25-35 grams of complete protein
Insoluble	Processed sugar	High carb; PM 30-45 grams of high-fiber carbohydrates including: Navy beans Squash Lentils Quinoa Buckwheat
Resistant	Pesticides

During the trial, participants checked in weekly with Dr Rezaie’s team for measurements of weight, body fat, and waist circumference, and to be given support and clarity on the dietary recommendations. At the end of the study, all measurements, including salivary cortisol and the HPAD severity quiz, were repeated.

Evaluating changes in cortisol rhythm required via salivary cortisol panels. I devised a process that scored each result in terms of deviation from ideal daily rhythm, as opposed to a total cortisol score. This was based on the fact that although salivary cortisol panels can accurately gauge HPA activity,¹⁴ correction is not always a matter of decreases in cortisol.

To show deviation from ideal cortisol, I assigned an ideal value calculated by determining a mid-range number based on a popular commercial laboratory’s reported optimal values:

Morning: 22 nmol/L
Noon: 13 nmol/L
Afternoon: 6 nmol/L
Midnight: 1 nmol/L

Then, for each of the 4 scores, I subtracted the patient’s score from the ideal value and turned the result into a positive integer that was used as the degree of variation. Finally, I totaled the 4 degrees of variation into a score representing the patient’s total cortisol variation from the ideal.

Table 2 shows an example of a hypothetical Patient X with a total cortisol variation of 21 points.

Table 2: Example of Scoring for Total Cortisol Variation

Collection Time	Patient X	Ideal	Variation
Morning	12	22	10
Noon	20	13	7
Afternoon	5	6	1
Midnight	4	1	3
Total Variation			21

Study Results

Over the course of 30 days, participants saw significant improvements in body weight, body fat, waist circumference, and HPA function (Table 3). In terms of HPA function, the average variations (pre and post) were not average cortisol values, but rather average deviations from ideal cortisol. Positive deviations (high cortisol) were treated in the same way as negative deviations (low cortisol). Many patients had cortisol that was abnormally high, but many also had cortisol that was abnormally low. If all 4 samples moved down in value, the deviation dropped, not the cortisol.

Table 3. Adrenal Reset Diet Study Results¹⁵

		Weight	BMI	Fat %	Waist
	Body Changes
Starting Average		182.3	29.4	35.42%	37.7
Ending Average		173.3	28.0	33.41%	35.6
Total Changes		-9.20	-1.46	-2%	-2.19
Percentage Change		-5.05%	-4.95%	-5.80%	-5.81%

	Adrenal Changes
Time of Measurement		7-9 AM	Noon-1 PM	5-6 PM	11 PM-Mid
*Ideal Cortisol (nmol/L)		22.0	13.0	6.0	1
†Average Variation Pre (nmol/L)		7.69	7.05	4.90	4.93
†Average Variation Post (nmol/L)		3.79	4.19	2.62	2.57
†Average Changes (nmol/L)		3.90	2.86	2.29	2.36
Percentage Change		50.8%	40.5%	46.6%	47.8%

	Total Variation Pre – 4 Scores Combined (nmol/L)				24.57
	Total Variation Post – 4 Scores Combined (nmol/L)				13.17
	Reduction in Cortisol Variation				53.59%

*Ideal cortisol values as reported by a commercial diagnostic laboratory

†Deviations from ideal cortisol

These initial results suggest that dietary change as a prescriptive monotherapy has the potential to improve HPAD. This is an encouraging, given the importance of HPA function to health and limitations of some current therapies.

Closing Comments

The main limitations of this trial include the lack of control group and the reliance on self-reported food intake. Given that weight-loss diets run the risk of worsening HPAD,³improved HPA function is a remarkable finding.

Hopefully, more controlled studies will be done using a multi-factorial approach to HPA repair, including diet, mind-body therapies, circadian hygiene, appropriate exercise, and targeted adaptogens.

Image Copyright: <a href=’https://www.123rf.com/profile_ankabala’>ankabala / 123RF Stock Photo</a>

Alan Christianson, is a Phoenix, Arizona-based naturopathic medical doctor specializing in natural endocrinology, with a focus on thyroid and adrenal disorders. He is the author of the bestselling Adrenal Reset Diet; The Complete Idiot’s Guide to Thyroid Disease; and Healing Hashimoto’s: A Savvy Patient’s Guide. As a child, cerebral palsy left him with seizures, poor coordination, and eventual obesity. Following a devastating comment by a classmate in 7th grade, he devoured dozens of books on health and created his own recovery plan. By 9^th grade he played varsity football and was an accomplished endurance runner. His experience taught him that becoming healthy through knowledge and persistence transforms both how you feel and how others treat you. Examples of media appearances include The Doctors, The Today Show, and Shape Magazine. When not maintaining a busy practice, he enjoys mountain unicycling, technical rock climbing, and watching the stars. Dr Christianson resides in Scottsdale, AZ, with his wife Kirin and their 2 children.

References:

Silverman MN, Sternberg EM. Glucocorticoid regulation of inflammation and its functional correlates: from HPA axis to glucocorticoid receptor dysfunction. Ann N Y Acad Sci. 2012;1261:55–63.
Tomiyama AJ, Mann T, Vinas D, et al. Low calorie dieting increases cortisol. Psychosom Med. 2010;72(4):357-364.
McKibbin PE, Cotton SJ, McMillan S, et al. Altered neuropeptide Y concentrations in specific hypothalamic regions of obese (fa/fa) Zucker rats. Possible relationship to obesity and neuroendocrine disturbances. Diabetes. 1991;40(11):1423-1429.
Sominsky L, Spencer SJ. Eating behavior and stress: a pathway to obesity. Front Psychol. 2014;5:434.
Frodl T, O’Keane V. How does the brain deal with cumulative stress? A review with focus on developmental stress, HPA axis function and hippocampal structure in humans. Neurobiol Dis. 2013;52:24-37.
Jefferies W. Safe Uses of Cortisol. 3rd ed. Springfield, IL: Charles C Thomas Pub Ltd; 2004.
Wilson J. Adrenal Fatigue: The 21^st Century Stress Syndrome. North Haledon, NJ: Smart Publications; 2001.
Brandão Neto RA, de Carvalho JF. Diagnosis and classification of Addison’s disease (autoimmune adrenalitis). Autoimmun Rev. 2014;13(4-5):408-411.
Katan M, Christ-Crain M. The stress hormone copeptin: a new prognostic biomarker in acute illness. Swiss Med Wkly. 2010;140:w13101.
Nader N, Chrousos GP, Kino T. Interactions of the circadian CLOCK system and the HPA axis. Trends Endocrinol Metab. 2010;21(5):277-286.
Gonnissen HK, Hulshof T, Westerterp-Plantenga MS. Chronobiology, endocrinology, and energy- and food-reward homeostasis. Obes Rev. 2013;14(5):405-416.
Chen CL, Willis BA, Mooney L, et al. Cortisol response to individualised graded insulin infusions: a reproducible biomarker for CNS compounds inhibiting HPA activation. Br J Clin Pharmacol. 2010;70(6):886-894.
Schwingshackl L, Hoffmann G. Nutr Metab Cardiovasc Dis. 2013;23(8):699-706.
Golden SH, Wand GS, Malhotra S, et al. Reliability of hypothalamic-pituitary-adrenal axis assessment methods for use in population-based studies. Eur J Epidemiol. 2011;26(7):511-525.