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Optimal DX FYI: Antioxidants, Adrenal Hormones, and Oxidative Stress

The adrenal glands produce hormones that are vital to life.

These include:

  • Aldosterone
    • Influences blood pressure and electrolyte balance
    • Regulated sodium and potassium balance
  • Cortisol
    • Participates in the stress response, immune function, and metabolism
  • Dehydroepiandrosterone (DHEA) and DHEA-S
    • A precursor to sex hormones estrogen and testosterone
    • Enhances stress tolerance
    • Low levels are associated with diabetes, metabolic syndrome, and decreased bone mineral density
  • Epinephrine and norepinephrine
    • Increase release of glucose and fatty acids for immediate energy
    • Increase bronchiole dilation

Adrenal gland structure and hormone production

Adrenal Insufficiency: Insufficient production of cortisol and/or aldosterone
  • Primary (adrenal)
    • Addison’s disease, insufficient cortisol and aldosterone
    • Causes include autoimmune adrenal gland damage, infection, genetic abnormalities
    • Characterized by weight loss, frailty, fatigue, low blood pressure, salt cravings, skin hyperpigmentation
  • Secondary (pituitary)
    • Insufficient pituitary production of adrenocorticotrophic hormone (ACTH)
    • ACTH stimulates adrenal cortisol synthesis
  • Tertiary (hypothalamus)
    • Caused by exogenous steroid medications
Adrenal Hyperfunction: Long-term excess cortisol exposure, aldosteronism
  • Cushing’s
    • Severe morbidity, weight gain (especially face and trunk), muscle weakness, thin skin, easy bruising, high blood pressure, glucose intolerance, mood swings, increased CVD risk
    • Exogenous Cushing’s caused by corticosteroid use
    • Endogenous Cushing’s caused by adrenal tumors, pituitary tumors, or ACTH-generating tumors elsewhere
  • Aldosterone
    • Primary aldosteronism

Chronic anxiety, unhealthy dietary choices, hormone dysregulation, and environmental pollution can trigger adrenal dysfunction.

Oxidative Stress

The adrenal glands are highly metabolically active and vulnerable to oxidative stress, which can significantly disrupt adrenal hormone synthesis. Oxidative stress occurs when the body’s antioxidant defenses are overwhelmed and are no longer able to neutralize free radical reactive oxygen species (ROS). The situation is exacerbated when excess cortisol, an adrenal glucocorticoid, creates oxidative stress of its own, perpetuating a dangerous cycle.

Oxidative stress damages lipids, proteins, and DNA, turns on inflammatory pathways, and causes cellular dysfunction, tissue damage, and organ impairment. Oxidative stress is linked to Parkinson’s, Alzheimer’s, cancer, and cardiovascular disease.

Both adrenal insufficiency (e.g., Addison’s) and adrenal hyperfunction (e.g., Cushing’s) are associated with oxidative stress, immune dysfunction, cognitive impairment, fatigue, and accelerated aging.

Adrenal hormonal imbalance-associated oxidative stress

Hormone

Imbalance

Effects on Oxidative Stress

Glucocorticoids

Excess (Cushing’s syndrome) or deficiency (Addison’s disease)

Reduced antioxidant defenses: decreased endogenous antioxidant synthesis (e.g., glutathione, SOD, catalase).

Increased ROS generation: Activation of NADPH oxidase stimulates ROS production (superoxide anions, hydrogen peroxide).

Impaired mitochondrial function: Impairment of mitochondrial activity, which results in increased ROS generation within the mitochondria.

Inflammation and oxidative stress: Immune system imbalance and promotion of chronic inflammation, linked to increased oxidative stress.

Mineralocorticoids

Excess (Hyperaldosteronism) or deficiency (Hypoaldosteronism)

Excess aldosterone can lead to increased activation of the renin-angiotensin-aldosterone system (RAAS), which is in relation with oxidative stress.

Mineralocorticoid imbalances can disrupt sodium and potassium balance, disrupting cellular homeostasis and causing oxidative stress indirectly.

Androgens

Excess (Hyperandrogenism) or deficiency (Hypoandrogenism)

Inflammation and oxidative stress: An imbalance in androgen levels can alter the immunological response and contribute to chronic inflammation, both of which lead to increased oxidative stress.      Mitochondrial dysfunction: Changes in testosterone levels can impair mitochondrial function and increase ROS generation, leading to oxidative stress.

Excess androgen levels can cause oxidative damage to reproductive organs, impacting fertility and reproductive health.

Antioxidants combat oxidative stress

Both endogenous and exogenous antioxidants help combat oxidative stress in the body. Their effect is optimized with a nutrient-dense diet high in antioxidants, regular exercise, physical activity, environmental toxins avoidance, smoking, and binge drinking.

Endogenous antioxidants

  • Catalase
  • Glutathione
  • Glutathione peroxidase
  • Superoxide dismutase (SOD)
  • CoQ10 (endogenous and exogenous)

Exogenous antioxidants

  • Carotenoids
  • Polyphenols
  • Probiotics
  • Selenium
  • Vitamin C and E
  • Zinc

Sources of different types of nutritional antioxidants

 

The role of nutritional antioxidants in Adrenal hormone function

 

Nutritional Antioxidant

Role in Adrenal Hormone Function

Vitamin C

Supports the production of androgens, glucocorticoids, and mineralocorticoids

Serves as a cofactor in the process by which cholesterol is transformed into pregnenolone

Vitamin E

Protects adrenal cells from oxidative stress
Possibly plays a function in regulating cortisol levels

Carotenoids

Carotenoids contained in several foods, beta-carotene and lycopene, act as antioxidants
Aiding in the reduction of oxidative stress in the adrenal glands

Selenium

Important in the synthesis of selenoproteins such as glutathione peroxidase, which protects adrenal cells from oxidative damage.

Zinc

Zinc is required for the synthesis, release, and general function of adrenal hormones
As an antioxidant, it protects cells from oxidative stress.

Polyphenols

Reduce oxidative damage and inflammation in the adrenal glands to help with adrenal hormone balance.

Coenzyme Q10

Plays a critical function in the cellular energy production process
Supports the overall function of the adrenal glands and may lessen oxidative stress.

Probiotics

Indirectly altering adrenal hormone balance and encouraging optimal function by mitigating oxidative stress and inflammation.

Hypothalamic-Pituitary-Adrenal (HPA) axis and role of selenium and ascorbic acid supplements

                                     

Health benefits of probiotics and their effects on brain, gut, and microbiome (BGM) axis modulating of HPA axis and cortisol release

The BGM axis network of routes that facilitate the exchange of information and signals encompasses neuronal elements (vagus nerve, neurotransmitters, and enteric nervous system), the HPA axis, and stress hormones like cortisol. Furthermore, immune mechanisms, specifically cytokines, contribute to this complex interplay. (SCFAs), Short-chain fatty acids; (ANS), autonomic nervous system; (ROS), reactive oxygen species; (HPA axis), Hypothalamic–pituitary–adrenal axis.

Role of nutritional antioxidants in alleviating adrenal hormone imbalance

Optimal Takeaways

  • Oxidative stress is a cause and a consequence of adrenal hormone imbalance.
  • Adrenal disorders include adrenal insufficiency and Cushing's syndrome.
  • Antioxidants (vitamin C, E, carotenoids, selenium, etc.) combat oxidative damage.
  • Nutritional antioxidants aid in restoring adrenal hormone function.
  • Antioxidants offer potential therapeutic benefits for adrenal hormone disorders.

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Reference

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).

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