All About Prednisone!
Prednisone: For a friend in need but a foe indeed
Prednisone, a synthetic corticosteroid drug, is perhaps the best example of a mixed blessing at best. It is an immunosuppressant commonly prescribed for many conditions, ranging from migraines to some cancers. It is also used after traumatic injuries, organ transplant surgery, to treat some ear problems and many gut problems. The most common uses for Prednisone are inflammatory and autoimmune conditions, both situations where the immune system is too active.
One aspect of intestinal function that defines inflammation during inflammatory or autoimmune disease is intestinal permeability. Our intestinal membranes are highly evolved to regulate the passage of some molecules and not others. Specific molecules form what are called “tight junctions” between the cells of the intestinal wall, and some molecules such as Zonulin specifically regulate permeability. If intestinal permeability increases and molecules of food are absorbed before digestion, the immune system may generate an antibody response, resulting in a food sensitivity that can cause ongoing inflammation if consumption is repeated. Prednisone is often used to treat conditions such as Crohn's disease, because the drug can inhibit the inflammatory cascade, specifically cytokines such as Tumor Necrosis Factor Alpha (or TNF-α) and others. Researchers have shown that while Prednisone can reduce intestinal permeability and bring some relief (Wild), using probiotics instead will also restore tight junction proteins such as Zonulin and Occludin (White). This makes the improvement both less risky and longer-lasting, as the probiotics improved the intestinal gut bacteria as well and these symbiont organisms help tame the immune system.
While Prednisone seems to provide relief or improvement with perhaps the widest range of problems of any class of drug, this improvement often is short-lived as side effects more severe than the initial problems can occur quite frequently. Many people on long-term Prednisone therapy find that it is quite challenging to reverse its adverse effects.
To understand the issues with Prednisone, it is important to first understand what glucocorticoids are and how they work. Naturally occurring glucocorticoids in the body activate receptors on cells, altering their glucose use and balance. This is part of how the autonomic nervous system addresses the needs of each cell in response to “fight or flight” stimuli, or simply to adjust for changes in activity and energy needs. In addition to regulating the glucose metabolism of virtually every cell in the body, glucocorticoids regulate immune function and some aspects of .
Cortisol is one example of a naturally occurring glucocorticoid, and is critical to the regulation of cell metabolism, immune function, circulation, and overall health. This natural glucocorticoid is also produced in response to stressful stimuli, by the adrenal glands located on the kidneys. If a person is stressed for too long a time, then adrenal fatigue and autonomic dysfunction can occur. Since cortisol is important for so many aspects of function and homeostasis, it is easy to see why stress is quite harmful to overall health!
Because Prenisone activates the same systems, its effects are quite profound. This is also why the side effects of Prednisone extend from bone loss to diabetes. Bone is constantly being “remodeled” according to physical forces such as gravity and muscle exertion. Cells called osteoblasts are tasked with laying down more bone mineralization, while osteoclasts remove minerals from bone where it isn't needed as much. This remodeling is called “Wolff's Law” after Dr. Julius Wolff, who observed the pattern of mineralization in the 19th century. Even low-dose Prednisone causes osteoporosis (Ton, Shah) and osteoporosis is a common side effect (Mitra, Shah) often resulting in bone fractures (Curtis). It is estimated that 20% of osteoporosis cases are secondary to glucocorticoid exposure (Mitra).
A process similar to Wolff's Law occurs with cartilage, as chrondrocytes grow more cartilage and physical processes of wear and tear reduce the cartilage. There exists a balance in healty individuals such that chondrocytes replace the cartilage that was used/eroded, and joints remain healthy. Prednisone alters this balance by altering how cartilage is formed, with different types of collagen that mimic aging cartilage forming (Dearden). The result is weaker cartilage that is more prone to injury. Prednisone eventually results in death (apoptosis) of chondrocytes, making the joint unable to repair the damage that results from normal “wear and tear”, with early joint degeneration being the outcome (Liu). A similar problem occurs with tendons, sometimes resulting in tendon rupture (deWolf).
The brain is also the site of Prednisone's unwelcome side effects, including reduced memory (Keenan, Fietta), mania, depression and suicidality (Fietta), psychosis, panic and delirium (Judd, Stojan). While these effects appear to often be reversible, they can also lead to more prescription medications to treat the symptoms, moving the patient further from a normal condition of homeostasis.
Another aspect of bone health that is affected by synthetic glucocorticoids such as Prednisone include osteonecrosis, or literally translated “bone death.” This condition occurs when a portion of bone no longer receives its blood supply—a side effect that makes sense when one considers that natural glucocorticoids normally help regulate blood supply to different body parts. Osteonecrosis is also called Avascular Necrosis, with the term “avascular” meaning “without blood circulation. Steroids, such as Prednisone are the most common cause of osteonecrosis (El Gamal). This can even occur with short-term low dose treatments (Kennedy).
Continued use of Prednisone or other synthetic glucocorticoids can also result in problems such as dependence, cataracts, and Cushingoid syndrome (a syndrome characterized by weight gain, fluid retention, central/abdominal weight gain, redness in the face and a full palette of additional symptoms. Medication is the most common cause, followed by tumors that produce hormones (https://en.wikipedia.org/wiki/Cushing%27s_syndrome)
Prednisone has been found to increase the risk of intestinal/digestive tract ulceration or perforation, particularly in some circumstances. This constitutes a potentially life-threatening complication, as a perforation allows gastrointestinal contents to enter the abdominal space, where sepsis or peritonitis can occur. For example, patients taking NSAID medication and also taking Prednisone have a seven-fold increased risk of gastrointestinal bleeding (ACG). There is also a strong association with perforated peptic ulcers in children being treated with Prednisone (Bickler). In a similar fashion, steroids increase the risk of upper gastrointestinal complications in adults, particularly when used with NSAIDS (Hernandez-Diaz). A common medical strategy to reduce the chances of a perforated ulcer is to block stomach acid production with an antacid (Boland). While this does reduce the chances of perforation, stomach acidity is needed for protein digestion (Berg). In addition, adding a proton pump inhibitor (acid blocker) results in dysbiosis of the small intestine and small intestinal bacterial overgrowth, itself a chronic debilitating condition (Fujimori).
Often discounted by physicians but critical for patients are the very common side effects of prednisone which include alteration to immune function, facial rounding, hirsutism (unwanted excess hair growth), lower carbohydrate tolerance, insomnia, restlessness, weakness, brain fog, acne, increased skin pigmentation and abdominal distress (Bollet).
In summary, Prednisone and other glucocorticoids are some of the most predictably dangerous drugs we have, and they should be used with extreme discretion and only if no safer alternative approaches are available. Natural alternatives should be used first in all but the most acute and critical of circumstances.
ACG: “Ulcers and Gastrointestinal Bleeding: Protecting your Health” from American College of Gastroenterology http://s3.gi.org/patients/pdfs/ulcerprotect.pdf
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