The Hidden Dangers of Corticosteroids
To regulate itself, the body often relies upon sensors that detect something amiss and then emit a signal that is amplified by the body so that a process can be set in motion to fix the issue that set the sensor off. One of the key signals the body relies upon are hormones, as small amounts of these molecules being released are often sufficient to change the internal state of the body drastically.
The hypothalamic-pituitary-adrenal (HPA) axis is the body’s central stress response system. It has three main components: the hypothalamus and pituitary gland in the brain, and the adrenal glands on top of the kidneys. When you experience stress, the hypothalamus releases corticotropin-releasing hormone (CRH), which signals the pituitary gland to secrete adrenocorticotropic hormone (ACTH). ACTH then travels through the bloodstream to the adrenal glands, prompting them to release the corticosteroid cortisol (the body’s primary stress hormone). Finally, once cortisol levels are high enough, they signal the brain to reduce CRH and ACTH production, creating a negative feedback loop that prevents over-activation of the stress response.
Cortisol, in turn, has a few key functions in the body:
Immune Modulation: Cortisol first enhances the immune system’s immediate response to threats (protecting the body during stress), then limits excessive immune activity to prevent autoimmunity. It does this partly by inhibiting pro-inflammatory cytokines (e.g., IL-1, IL-6) and reducing T-cell activity. Over time, this shifts to immune suppression, making synthetic corticosteroids, a popular treatment for inflammation and autoimmunity.
Note: at lower doses, this transition from immune stimulation to immune suppression takes much longer, whereas at high doses it’s faster (hence why high steroid doses are given for dangerous autoimmune flares).
Blood Sugar: When blood sugar is low, cortisol raises it by stimulating gluconeogenesis in the liver, mobilizing amino acids (from muscle) and fatty acids (from fat) for glucose production, and reducing insulin sensitivity in tissues like muscle and fat. Excessive cortisol can lead to diabetes, abdominal fat accumulation (obesity), weight gain, insulin resistance, and cardiovascular issues.
Connective Tissues: Cortisol promotes protein catabolism (breakdown) in muscles, providing substrates for glucose synthesis and inhibiting collagen synthesis. Excessive cortisol causes muscle wasting, bone loss (e.g., osteoporosis or osteonecrosis), poor wound healing (which is also a result of immune suppression), skin thinning, easy bruising, and purple striae.
Circulation: Cortisol raises blood pressure by increasing sodium and water retention, sensitizing blood vessels to epinephrine and norepinephrine. This causes vasoconstriction and an increased heart rate while also damaging the blood vessel lining. This elevates the risk for cardiovascular disease1,2,3 (e.g., a one-standard deviation increase in morning plasma cortisol is linked to an 18% higher risk of future cardiovascular events).
Cognition: Cortisol modulates arousal, attention, and memory consolidation. Chronic excess corticosteroids (from either endogenous cortisol or synthetic steroids) impair hippocampal function, causing memory deficits, increased pain sensitivity, attention issues, cravings for high-calorie foods, substance abuse, and, rarely, psychosis.
HPA Axis Dysfunction: Since the HPA axis is regulated by cortisol levels, once natural or synthetic corticosteroids are chronically elevated, the HPA axis becomes desensitized, leading to excessive cortisol secretion or loss of the ability to secrete cortisol when needed. This in turn creates many issues such as those associated with chronically excessive cortisol or varying degrees of fatigue (e.g., due to the adrenal glands not secreting cortisol when needed).
Note: excessive cortisol can also cause other effects such as blood electrolyte imbalances, alkalosis, cataracts, and glaucoma.
Because of this, many argue excessive cortisol secretion and HPA axis dysfunction (e.g., due to chronic stress, poor diet, poor sleep, alcoholism, too many stimulants like caffeine, social isolation, a lack of exercise, or irregular daily rhythms) is a root cause of disease (e.g., the metabolic syndrome afflicting our country). As such, they advocate for lifestyle practices that counteract these HPA axis-disrupting factors, and in many cases significant health benefits follow the adoption of those practices.
Corticosteroids
The hormone cortisol belongs to a class of steroids known as corticosteroids due to its release by the cortex of the adrenal glands. While many related corticosteroids (henceforth referred to as “steroids”) exist within the body, the body’s primary ones are cortisol (a glucocorticoid) and aldosterone, a mineralocorticoid that regulates blood pressure, volume, and electrolyte balance.
In 1946, the first synthetic steroid (cortisone) was synthesized. Two years later, enough had been produced to test on it a human, where it was discovered to improve rheumatoid arthritis symptoms (which won the 1950 Nobel Prize) and was immediately hailed as a ‘wonder drug.’ Before long, it was discovered that other inflammatory syndromes also responded to cortisone, and a rush of other steroids hit the market:
Following its success in rheumatoid arthritis, steroids (e.g., prednisone, hydrocortisone) were rapidly adopted for a wide range of inflammatory and autoimmune disorders, including systemic lupus erythematosus, inflammatory bowel disease, and multiple sclerosis, due to their ability to suppress immune-mediated tissue damage.
In the early 1950s, steroids were hailed as a revolutionary treatment for those conditions (and hence widely prescribed), with new steroids (e.g., prednisone) being rapid
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