Targeted Natural Interventions
Given the crucial role of the adrenal glands in maintaining normal body function and the extended (often life-long) treatment needed for adrenal disorders, there is a pressing need for alternative strategies that can help people cope with the debilitating effects of Cushing’s syndrome, Addison’s disease, and related conditions. Research has shown that several natural compounds have an impact on adrenal physiology (Anderson 2008). In this section, several nutritional interventions that may play a supportive role in the treatment of adrenal disorders will be reviewed. Additional discussion about natural compounds that may support adrenal health (eg, in “adrenal fatigue”) is available in the Stress Management protocol.
Nutritional interventions in Cushing’s syndrome
Melatonin is a hormone secreted by the pineal gland in the brain during the night. It plays a role in inducing sleep and regulating the circadian rhythm (Dominguez-Rodriguez 2012; Cajochen 2003). Cushing’s syndrome has been associated with low melatonin levels and disruption of its circadian secretion (Soszynski 1989; Tomova 2008). A study assessing the effects of melatonin on adrenal hormone production in healthy men found that melatonin reduced cortisol secretion in response to an ACTH stimulation test, but did not affect the levels of other steroid hormones. This suggests that melatonin may have a direct action on the adrenal glands (Campino 2008).
Vitamin D & Calcium
Vitamin D supports calcium absorption and its deficiency can contribute to osteoporosis. In Cushing’s syndrome, high cortisol levels lead to osteoporosis (Tritos 2012). Similarly, long-term glucocorticoid treatment can also result in osteoporosis. Vitamin D supplementation is considered to be an important step for preventing osteoporosis due to glucocorticoid treatment (Davidson 2012). A group of researchers analyzed studies conducted over 33 years and concluded that vitamin D and calcium supplements should be given to people receiving long-term corticosteroids (Amin 1999). A second analysis of studies conducted between 1970 and 2011 showed that adults who received glucocorticoid treatment had less than optimal levels of vitamin D, which were inadequate for the prevention of osteoporosis (Davidson 2012). Thus, vitamin D supplements may be useful in people with Cushing’s syndrome who have high cortisol levels, as well as in Addison’s disease where long-term hormone replacement is necessary.
Potassium levels are known to be low in individuals with Cushing’s syndrome, and low potassium levels are a significant determinant of cardiovascular complications in this population (PubMed Health 2011c; Takagi 2009). Hence, potassium supplements could be useful in people with Cushing’s syndrome. However, people on ketoconazole treatment for Cushing’s syndrome should avoid potassium supplements since ketoconazole treatment can also increase potassium levels (Sonino 1991).
Additional support for Cushing’s disease
The following interventions may provide support for Cushing’s disease, though more studies are needed to confirm their efficacy in humans.
- Vitamin A
Laboratory and animal studies have shown that retinoic acid (a form of vitamin A) decreases ACTH synthesis and decreases proliferation (or multiplication) and survival of pituitary tumor cells (Pozza 2012; Paez-Pereda 2011). It also decreased proliferation and corticosterone production in adrenal cortex cells (Paez-Pereda 2001). In one study, animals with Cushing’s disease were given either ketoconazole or retinoic acid. After 90 and 180 days of treatment there was a significant decrease in ACTH levels in the retinoic acid treated animals compared to no change in the ketocanozole group. The retinoic acid treated animals also showed improvements in clinical signs and survival time, and a significant reduction in pituitary tumor size (Castillo 2006).
Curcumin, one of the active constituents of Curcuma longa (a spice commonly used in South Asian cooking), has been widely studied for its therapeutic properties. ACTH-secreting pituitary tumors are one of the most common causes of Cushing’s disease (Yaneva 2010). Using pituitary tumor cells from mice, a laboratory study showed that curcumin suppresses ACTH secretion, stops tumor cell growth and proliferation, and induces the death of tumor cells (Bangaru 2010).
Nutritional interventions in Addison’s disease
Licorice (Glycyrrhiza glabra) has been used for hundreds, if not thousands of years in both Eastern and Western cultures to treat myriad illnesses and to increase physical endurance (Davis 1991). Licorice may also protect against DNA damage induced by carcinogens (cancer-causing compounds) and induce the death of cancer cells (Wang 2001). It was used for the treatment of stomach and duodenal ulcers until the advent of modern anti-ulcer medicines. It was in the context of its use as an anti-ulcer compound that the mineralocorticoid-like actions of licorice were noticed. People taking licorice extracts for extended periods of time showed sodium and water retention and increased excretion of potassium (Davis 1991). This effect was also observed in animal experiments (Souness 1989). Further research showed that licorice appeared to be successful in reversing the effects of Addison’s disease (Davis 1991). With advances in scientific research in the 1980s, it was found that a chemical compound, called glycyrrhetinic acid, present in licorice causes changes in adrenal steroid metabolism, resulting in increased levels of corticosterone in animals and cortisol in humans (Davis 1991).
Licorice is also known to regulate the HPA axis. Healthy male and female volunteers who consumed a licorice-containing confectionary showed increased levels of DHEA and testosterone in the saliva (Al-Dujaili 2011). Thus, licorice may also be useful for androgen deficiency in adrenal disorders. In one study, people with Addison’s disease on cortisone replacement therapy who were given licorice were found to have increased cortisol tissue levels (Methlie 2011).
Individuals with Addison’s disease, in addition to cortisol insufficiency, have been reported in some studies to have low DHEA levels, which researchers speculate may contribute to decreased quality of life. A small clinical study of DHEA supplementation among Addison’s patients revealed an immunomodulatory role for the hormone in this population, whereby supplementation appeared to improve regulation of inflammation and immune response (Coles 2005). In another clinical trial, men and women aged 25-69 with Addison’s disease were given DHEA daily for 12 weeks. Their DHEA levels increased from below normal to a normal range for healthy young people (Hunt 2000). In a year-long study, 106 people with Addison’s disease were given 50 mg of DHEA daily or no supplement. The group receiving DHEA showed increased levels of circulating DHEA-S and androstenedione, a reversal of bone density loss at the neck of the femur (thigh bone), and improved emotional health (Gurnell 2008). DHEA supplementation may also counter some consequences of adrenal insufficiency that arise secondarily to impaired pituitary gland function (Zang 2008).
There are several variables that can influence DHEA levels among individuals with adrenal dysfunction, whether due to Addison’s or Cushing’s, and DHEA supplementation may not be ideal for everyone with impaired adrenal function. Therefore, a diligent approach entails testing blood levels of DHEA-S, a major metabolite of DHEA, to determine if DHEA concentrations are outside the optimal range and initiating supplementation if an insufficiency or deficiency is observed. Life Extension suggests an optimal DHEA-S level of 350 – 490 µg/dL in men and 275 – 400 µg/dL in women.
Pantothenic acid (vitamin B5)
Pantothenic acid (vitamin B5) plays a role in the synthesis and maintenance of co-enzyme A (CoA), a crucial cofactor for many biological enzymatic reactions and a primary component of lipid and carbohydrate metabolism (Horvath 2009). Pantothenic acid is thought to be needed to maintain normal adrenal structure and function, as the administration of pantothenic acid to deficient animals improves adrenal function (Kelly 1999). Adrenal gland cells from rodents treated with pantothenic acid produced higher levels of corticosterone and progesterone than adrenal cells from rats that did not receive treatment (Jaroenporn 2008).
Prolonged stress from physical, mental, or environmental causes has deleterious effects on the body, including increased levels of cortisol, reduced immune function, and a disruption of the gastrointestinal microflora (beneficial bacteria) (Kelly 1999). Pantothenic acid administered to human subjects with various diseases better controlled the increase in cortisol metabolites in the urine following ACTH stimulation. This suggests pantothenic acid can modulate cortisol secretion in response to stress (Kelly 1999).
Coenzyme Q10 (CoQ10)
Coenzyme Q10, comes in the form of ubiquinone or ubiquinol, is essential for cellular energy production. It has antioxidant properties and protects cell membranes from damage. It is also commonly taken as an anti-aging supplement and to increase endurance in athletes (Mancini 2011; Lopez-Lluch 2010). When coenzyme Q10 is utilized as an antioxidant within the body, its availability for energy production may decrease (Mancini 2011). This is the rationale behind the dietary replenishment of coenzyme Q10 in many disease conditions. Preliminary data suggest that adrenal hormone secretion is related to coenzyme Q10 levels. Analysis of coenzyme Q10 levels in people with irregular pituitary-adrenal axis function showed that coenzyme Q10 levels are considerably lower in people with isolated decreases in adrenal function compared to people with adrenal hyperplasia or multiple pituitary deficiencies (Mancini 2005). The ubiquinol form of coenzyme Q10 has been shown to absorb better into the bloodstream than ubiquinone.