Research Blog

Optimal DX Supplement Series: Adrenal Hypofunction/Adrenal Insufficiency

Adrenal hypofunction or insufficiency is characterized by the body’s inability to maintain adequate or optimal production of adrenal hormones, including cortisol, adrenaline, and aldosterone.

Chronic activation of the HPA axis can lead to adrenal exhaustion and low adrenal hormone levels (Anderson 2008). Oxidative stress can contribute to adrenal dysfunction and insufficiency. Endogenous antioxidants, including glutathione, glutathione peroxidase, catalase, and superoxide dismutase, and exogenous antioxidants, including vitamins C, E, carotenoids, selenium, and zinc, help counteract oxidative stress and protect adrenals (Patani 2023).

Adrenal insufficiency can affect the body’s ability to respond to stress and maintain essential life functions. It can also lead to symptoms such as chronic fatigue, chronic infections, cognitive problems, and inflammation (Stengler 2016).

Source: Patani, Anil et al. “Harnessing the power of nutritional antioxidants against adrenal hormone imbalance-associated oxidative stress.” Frontiers in endocrinology vol. 14 1271521. 30 Nov. 2023, doi:10.3389/fendo.2023.1271521 This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).

Supportive Supplements

Adaptogens

Adaptogen is a term applied to herbs that normalize physiology and encourage non-specific resistance to stressors (Anderson 2008). They are associated with improving the body’s ability to adapt to stress and normalize metabolic functions (Todorova 2021).

Ashwagandha (Withania somnifera)
250 mg of standardized extract once or twice daily (Stengler 2016)
  • Extract doses can range from 225 to 1,250 mg per day for 6 to 8 weeks to reduce feelings of stress and anxiety and to decrease fatigue, sleeplessness, and stress hormone levels (ods 2023; Abedon 2008; Lopresti 2019).
  • Whole root granules of 12,000 mg/day (equivalent to 6,000 mg of root powder) have also been used (ODS 2023).
Siberian ginseng (Eleutherococcus senticosus)
100 to 300 mg/d extract (Stengler 2016)
  • Demonstrated effects on stress-induced fatigue, immune changes, and corticosterone elevations in an animal model of stress (Kimura 2004).
  • Improvements in mental health and social functioning in the elderly after 4 weeks of 300 mg dried extract per day (Cicero 2004).
Holy basil (Ocimum tenuiflorum)
125 mg twice daily of a standardized extract (Lopresti 2022)
  • Supplementation associated with improvements in Perceived Stress Scale and Profile of Mood States, Athens Insomnia Scale scores; buffered stress response to Maastricht Acute Stress Test; lower salivary cortisol, amylase, blood pressure, and subjective stress ratings (Lopresti 2022).
Rhodiola rosea
200 mg/d standardized extract standardized (Anghelescu 2018)
  • A standardized extract (200 mg per day for 12 weeks) improved performance speed and task accuracy in situations of simulated multi-tasking (Heldmann 2016).
  • Supplementation of 170 mg/d of extract containing approximately 4.5 mg salidroside for 14 days reduced fatigue in under stressful conditions (Darbinyan 2000).
  • A literature review found that 200 mg/d of a standardized extract helps normalize the release of stress hormones while boosting energy metabolism (Anghelescu 2018).

B-complex vitamins

50 to 100 mg/d (Stengler 2016)

  • B vitamins are required for steroid biosynthesis in the adrenal cortex (Anderson 2008).
  • Note: High levels of B6 may have neurological side effects; use under the guidance of a health professional.

Antioxidants:

Vit C – 1,000 mg two to three times daily (Stengler 2016); Vit E (as RRR-α-tocopherol) – 150 mg/d

  • Vitamins C and E help protect the adrenals from free radical damage for optimal functioning (Anderson 2008).
  • Vitamin E alleviated adverse effects of immobilization stress in an animal model (Asir 2022)

Licorice root

500 mg two to three times daily (Stengler 2016)

  • May increase cortisol levels by inhibiting an enzyme that converts cortisol into cortisone effects (Omar 2012).
  • Note: Due to its hypertensive effects, licorice must be used with caution and oversight; use it under the guidance of a health professional.

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References

Abedon, Bruce et al. "A standardized Withania somnifera extract significantly reduces stress-related parameters in chronically stressed humans: a double-blind, randomized, placebo-controlled study." JANA 11 (2008): 50-56.

Anderson, D. “Assessment and nutraceutical management of stress-induced adrenal dysfunction.” Integrative Medicine 7.5 (2008): 18-25.

Anghelescu, Ion-George, et al. "Stress management and the role of Rhodiola rosea: a review." International Journal of Psychiatry in Clinical Practice 22.4 (2018): 242-252.

Aşır, F., Y. Nergiz, and A. Pala. "Vitamin E protected the mouse adrenal gland against immobilization stress." Polish Journal of Veterinary Sciences (2022): 447-454.

Cicero, Arrigo Francesco Giuseppe, et al. "Effects of Siberian ginseng (Eleutherococcus senticosus maxim.) on elderly quality of life: a randomized clinical trial." Archives of Gerontology and Geriatrics 38 (2004): 69-74.

Darbinyan, V., et al. "Rhodiola rosea in stress induced fatigue—a double blind cross-over study of a standardized extract SHR-5 with a repeated low-dose regimen on the mental performance of healthy physicians during night duty." Phytomedicine 7.5 (2000): 365-371.

Heldmann, M., et al. "EP 116. Impact of Rhodiola Rosea extract WS1375 on electrophysiological correlates of attention allocation in a dual task paradigm." Clinical Neurophysiology 127.9 (2016): e290.

Kimura, Yoshiyuki, and Maho Sumiyoshi. "Effects of various Eleutherococcus senticosus cortex on swimming time, natural killer activity and corticosterone level in forced swimming stressed mice." Journal of Ethnopharmacology 95.2-3 (2004): 447-453.

Lopresti, Adrian L et al. “A randomized, double-blind, placebo-controlled trial investigating the effects of an Ocimum tenuiflorum (Holy Basil) extract (Holixer™) on stress, mood, and sleep in adults experiencing stress.” Frontiers in Nutrition vol. 9 965130. 2 Sep. 2022, doi:10.3389/fnut.2022.965130

Lopresti, Adrian L et al. “An investigation into the stress-relieving and pharmacological actions of an ashwagandha (Withania somnifera) extract: A randomized, double-blind, placebo-controlled study.” Medicine vol. 98,37 (2019): e17186. doi:10.1097/MD.0000000000017186

ODS Fact sheet for health professionals. Ashwagandha: Is it helpful for stress, anxiety, or sleep? National Institutes of Health Office of Dietary Supplements. Accessed June 18, 2024. https://ods.od.nih.gov/factsheets/Ashwagandha-HealthProfessional/

Olsson, Erik M et al. “A randomised, double-blind, placebo-controlled, parallel-group study of the standardised extract shr-5 of the roots of Rhodiola rosea in the treatment of subjects with stress-related fatigue.” Planta medica vol. 75,2 (2009): 105-12. doi:10.1055/s-0028-1088346

Omar, Hesham R et al. “Licorice abuse: time to send a warning message.” Therapeutic advances in endocrinology and metabolism vol. 3,4 (2012): 125-38. doi:10.1177/2042018812454322

Patani, Anil et al. “Harnessing the power of nutritional antioxidants against adrenal hormone imbalance-associated oxidative stress.” Frontiers in Endocrinology vol. 14 1271521. 30 Nov. 2023, doi:10.3389/fendo.2023.1271521

Stengler M, et al. Prescription for Natural Cures: A Self-care Guide for Treating Health Problems With Natural Remedies Including Diet, Nutrition, Supplements, and Other Holistic Methods. Third ed. Turner Publishing Co, 2016.Todorova, Velislava et al. "Plant adaptogens—History and future perspectives." Nutrients, 13.8 (2021): 2861.

Todorova, Velislava et al. "Plant adaptogens—History and future perspectives." Nutrients, 13.8 (2021): 2861.

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