Potential and Dangers of Prednisone
Prednisone is a synthetic corticosteroid used particularly for its anti-inflammatory effects. Prednisone’s ability to target many pathways in the inflammation process makes it the standard treatment for a wide variety of diseases. But, prednisone use can cause severe side effects. Read on to learn more and discover natural alternatives.
Disclaimer: By writing this post, we are not recommending this drug. Some of our readers who were already taking the drug requested that we commission a post on it, and we are simply providing information that is available in the clinical and scientific literature. Please discuss your medications with your doctor.
What is Prednisone?
Prednisone is a drug used to suppress the immune system and decrease inflammation. Prednisone can be taken alone or as part of a treatment plan with other drugs. Prednisone is available in the following forms:
- Rayos (extended-release tablet), which lasts for a longer time
- Delayed release tablet (starts to act only after 4-6 hours) [R]
- Intensol (prednisone solution)
- Generic prednisone tablets
- Generic prednisone solution
Prednisone should not be confused with methylprednisolone or prednisolone. Methylprednisolone is also available for IV use (Solu-Medrol, Depo-Medrol), unlike prednisone. And although all 3 are similar, the dosing and bioavailability differ [R, R].
Prednisone Mechanism of Action
Prednisone mimics the action of cortisol. Cortisol is a naturally occurring steroid hormone produced by the adrenal cortex. Before having an effect (via glucocorticoid receptors), prednisone first needs to be activated in the body. This happens while the drug travels from the gut to the liver, during which it becomes prednisolone — the active form [R, R]. As a corticosteroid, prednisone weakens the immune system’s inflammatory response through various pathways including:
- Blocking leukocyte response at the site of inflammation [R, R]
- Blocking inflammatory compounds (such as prostaglandins, leukotrienes, NF-κB, and AP-1) [R, R]
- Reducing the activity of genes that code for inflammatory compounds (cytokines, chemokines, inflammatory receptors, and proteins) [R]
- Activating anti-inflammatory genes (such as SLPI, MKP-1, IkB-a, GILZ) [R]
Uses of Prednisone
1) Rheumatoid Arthritis
In a study of 81 patients (double-blind randomized controlled trial) with rheumatoid arthritis (RA), 10 mg per day prednisone improved arthritic symptoms, reduced the need for other drugs, and reduced joint damage compared to placebo in the first 6 months. At 12 and 24 months, these effects weaned off; only improved grip strength and reduced tenderness remained noticeable [R].
In a study of 350 patients with RA (double-blind randomized controlled trial), modified-release (MR) prednisone 5 mg/day in addition to their current antirheumatic drug improved arthritic symptoms, reduced severity of disease, and increased physical function compared to placebo [R].
In an uncontrolled study of 89 patients with acute ulcerative colitis, treatment with 40-80 mg prednisone completely resolved symptoms in 47% of severe colitis, 80% in moderate colitis, and 84% in mild colitis [R].
In a study of 205 patients with ulcerative colitis (double-blind randomized controlled trial), 40 mg/day prednisolone improved symptoms faster than 20 mg/day fluticasone propionate within 2 weeks [R].
3) Respiratory Problems
In a study of 100 children with severe acute asthma (double-blind randomized controlled trial), 2 mg per kg prednisone improved breathing and reduced hospital visits better than another corticosteroid inhaled (2 mg fluticasone); both were given along with another asthma drug (bronchodilator) [R].
In a study of 285 children aged 6-14 years old (double-blind randomized controlled trial), the use of alternate-day prednisone therapy of 1 mg per kg for 24 months helped patients with mild to moderate symptoms of a genetic disorder that affects the lungs (cystic fibrosis) [R].
In a study of 785 pneumonia patients (double-blind randomized controlled trial), prednisone therapy of 50 mg per day for 1 week resulted in quicker improvement [R].
People with purpura experience bleeding under the skin, skin spotting or discoloration.
In purpura, the immune system attacks platelets, causing a low platelet count and reduced blood clotting. In a pilot study of 4 mg per kg/day prednisone, 22 out of 25 children with purpura improved, with an increase in platelet count [R].
In a study of 53 children with purpura (acute immune thrombocytopenic purpura), prednisone 4 mg per kg/day was as effective as an initial therapy [R].
In a study of 171 patients (double-blind randomized controlled trial) with purpura, prednisone 1 mg per kg/day was given for 2 weeks followed by a weaning period of 2 weeks. This reduced stomach and joint pain, and improved kidney symptoms [R].
Prednisone is currently part of the standard treatment for lymphocytic leukemia, most effective when used in combination with other drugs. Lymphocytic leukemia is a type of cancer that affects white blood cells (lymphocytes) in the bone marrow.
In a study of 96 patients with chronic lymphocytic leukemia (randomized controlled trial), the combination of 0.5 mg per kg/day prednisone + monthly chemotherapy medication (chlorambucil) showed the greatest reduction in disease severity (compared to prednisone-alone or prednisone+daily chlorambucil) [R].
Recently, studies compared prednisone with another steroid, dexamethasone, for lymphocytic leukemia and got mixed results. In some, dexamethasone was more effective, while in others there was no difference [R, R, R].
Lupus is an autoimmune disease and the goal of treatment is to reduce an overactive immune response. Since prednisone suppresses the immune system, it is one of the main treatment options for various types of lupus, in combination with other drugs [R].
In a study of 111 patients with lupus (systemic lupus erythematosus) and active kidney inflammation (glomerulonephritis) (randomized controlled trial), a combination of prednisone and another immune response-reducing drug, cyclophosphamide, protected the kidneys better than prednisone alone [R].
7) Autoimmune Hepatitis
Prednisone is one of the main treatment options for autoimmune hepatitis (AIH). In AIH, the immune system attacks liver cells and causes liver inflammation [R].
In a review (of 11 randomized controlled trials), both prednisone alone and in combination with another drug that suppresses the immune system (azathioprine) was effective in reducing symptoms, liver inflammation, and returning liver enzyme levels to normal. But the combination achieved better results [R].
8) Inflammatory Diseases
Polymyalgia Rheumatica (PMR) is an inflammatory condition that causes muscle pain and stiffness in the neck, shoulders, and hips.
In one review (of various glucocorticoid treatments for patients with PMR), an initial dose of 15 mg/day prednisone was effective in reducing PMR symptoms [R].
Side Effects of Prednisone
1) Increased Risk of Bone Fractures
In a study (cross-sectional) of 74 rheumatoid arthritis patients, long-term prednisone treatment of 10 mg/day increased the frequency of spine deformities in postmenopausal women.
In a large study (retrospective cohort) of 244,235 patients (with 244,235 matched controls), oral corticosteroids like prednisone increased fracture frequency. Higher prednisolone (the active form of prednisone) doses were linked to greater risk. When patients stopped taking these drugs, the risk of fractures rapidly returned to normal [R].
In a study (prospective cohort) of 539 lupus patients, a total dose of 36.5 g prednisone (equivalent to 10 mg/day prednisone for 10 years) was associated with a 2.5-fold increase in the risk of osteoporotic fractures [R].
2) May Cause Mood Disorders
In a (prospective cohort) study of 80 patients on at least 20 mg/day prednisone, 42 patients experienced neuropsychiatric disorders – anxiety, irritability, euphoria, hyperactivity, depression, or manic episodes – with 5 cases requiring hospitalization [R].
In a case study of 20 patients taking 7.5 mg/day prednisone, there was a 60% risk of mood or anxiety disorder caused by corticosteroid use [R].
Out of 12 patients in one study (prospective cohort), 9 reported behavioral changes, especially increased hypomania – feelings of irritability, feeling high, talkativeness – when taking 80 mg prednisone [R].
In a study of 101 patients taking 5 – 60 mg prednisone, 20% of patients reported mood alteration [R].
3) Increases Risk of Infections
In a study of 697 patients with acute lymphoblastic leukemia (retrospective review), prednisone treatment (maximum dose 60 mg/day) during the incubation period of the chicken pox virus (varicella) increased the severity of varicella infection [R].
In a study of 233 patients with lupus (retrospective), prednisone use of ≥ 40 mg/day had a 5-fold increase in infection frequency in comparison to no prednisone use [R].
4) May Cause Cataracts
In 58 children receiving prednisone for inflammatory bowel disease, 12 developed cataracts (compared to no cataracts found in 58 controls) [R].
In a prospective cohort study of 539 lupus patients, a total dose of 36.5 g prednisone (equivalent to 10 mg prednisone daily for 10 years) was associated with almost a 2-fold increase in cataracts [R].
5) Increases Risk of Cardiovascular Disease
In a prospective cohort study of 539 lupus patients, a cumulative dose of 36.5 g prednisone (equivalent to 10 mg prednisone daily for 10 years) was associated with a 1.7-fold increase in chest pain, heart attack, and artery bypass procedures. High dose prednisone was associated with a 1.2-fold increase in stroke and bone tissue death due to low blood supply [R].
6) Increases Blood Glucose Levels
In a 785 patient study of prednisone and pneumonia, 19% of patients taking 50 mg/day prednisone experienced increased glucose levels that required insulin treatment (compared to 11% of placebo-patients) [R]
7) May Cause Skin Changes
In a (double-blind randomized controlled trial) study of 80 patients on at least 20 mg/day prednisone, 37 patients experienced skin disorders such as unwanted hair growth, thinning skin, spontaneous bruising, and changes in wound healing [R].
8) Increases Muscle Cramping And Weakness
In a cohort study of 80 patients on at least 20 mg/day prednisone, 32.5% of patients reported muscle cramps and 15% of patients reported muscle weakness [R].
9) May Cause Menstrual Disorders
In a cohort study of 80 patients on at least 20 mg/day prednisone, 39% of women (premenopausal) experienced menstrual disorders such as irregular or shorter periods and less menstrual bleeding [R].
10) May Cause Stomach Problems
11) Increases Fluid Retention
In a study of 101 patients taking 5 – 60 mg prednisone, 33 patients experienced fluid retention and 13 patients experienced increased urination [R].
12) May Cause Insomnia
In a study of 101 patients taking 5 – 60 mg prednisone, 13 patients reported insomnia [R].
Adverse side effects are common even during short-term prednisone therapy. In a retrospective cohort study, patients given multiple corticosteroid prescriptions had increased adverse side effects, regardless of dose or duration [R].
Contraindications of Prednisone
Prednisone should not be taken by anyone who has experienced a hypersensitivity to the drug or any of its other components.
Prednisone Use During Pregnancy and Breastfeeding
Prednisone should not be used if you are pregnant. Only under certain circumstances where the benefits outweigh the potential risk to the fetus should prednisone be used and this should be determined on a case by case basis. In the old FDA categorical system, it was listed as a category C, with some preparations having a category D rating [R].
Prednisone has been found in breast milk and it is not recommended to take the drug if you are breastfeeding. Again, under certain circumstances where the potential benefits outweigh any potential risks to the fetus should it be used [R].
The potential risk to the fetus and to children are thought to be minimal, however, if prednisone use can be avoided, it is best to do so. More research needs to be done to determine how dangerous prednisone actually is during pregnancy and breastfeeding.
Drug Interactions of Prednisone
- Estrogen increases the effect of prednisone (decreased metabolism)
- Anti-seizure and sedating drugs (barbiturates, phenytoin, carbamazepine) decrease the effect of prednisone (increased metabolism)
- Antibiotics (ketoconazole, macrolides) increase the effect of prednisone (decreased metabolism)
Other drugs that may interact with prednisone include [R]:
- Amphotericin B
- Anticholinesterase Agents
- Anticoagulants (warfarin)
- Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)
Prednisone and Vaccines
Some studies show that prednisone treatment can be unsafe or reduce the effectiveness of vaccines, but others show no difference.
In a study of 30 nephrotic patients (prospective cohort study), high-dose prednisone therapy (initially 60 mg/m²/day for 1 month) showed no difference in pneumonia vaccine response compared to controls [R].
In a study of 50 asthmatic patients (prospective cohort study) prednisone treatment (2 mg per kg/day for 5 days) showed no significant difference in influenza vaccine response compared to controls [R].
In 24 patients with lupus (with 24 age-matched controls), prednisone treatment (≥ 10 mg/day) showed a decreased immune response to the influenza vaccine [R].
The Center for Disease Control (CDC) recommends that individuals with severely suppressed immune systems should not get live vaccines. The CDC defines an immunosuppressive steroid dose at ≥ 20mg /day prednisone for over 2 weeks [R].
Forms and Dosage of Prednisone
Prednisone is available as immediate- and delayed-release tablets and also as a solution.
Prednisone dosing varies widely from 1 mg to 80 mg depending on the disease being treated, whether the condition is acute or chronic, and the response to treatment.
One of the main challenges is finding the right dose and duration of treatment while minimizing the risk of side effects.
Slowly decreasing the dose rather than immediately stopping prednisone – tapering – is often used and is linked to better treatment outcomes and fewer side effects. In a review of 30 studies of polymyalgia rheumatica, slow prednisone dose tapering of less than 1mg/month decreased the frequency of relapse [R].
Prednisone mimics the action of cortisol. Cortisol is a naturally occurring steroid hormone produced by the adrenal cortex. Therefore, prednisone is often used as replacement therapy for adrenal insufficiency (AI). In AI, the adrenal gland fails to produce enough steroids, including cortisol and can have various causes [R]
Although seemingly counterintuitive, prednisone use may actually cause adrenal insufficiency. In the hypothalamic-pituitary-adrenal (HPA) axis, increasing prednisone levels will trigger negative feedback in the hypothalamus. This ultimately results in a decreased cortisol production in the adrenal cortex.
The HPA axis is usually able to recover quickly from short-term corticosteroid therapy of fewer than 10-14 days. However, if given for more than 2 weeks, it’s better to slowly reduce the dose to allow the HPA axis sufficient time to recover [R].
Natural Alternatives to Prednisone
There are many natural alternatives to prednisone – herbs, mushrooms, minerals, and vitamins – all can help lower inflammation and pain in the body. This list is not comprehensive, but we have provided a breakdown of the top ones that act most similarly to prednisone (comparing the mechanism of action), have fewer side effects, and can be used to help people suffering from similar diseases like the ones prednisone is prescribed for.
Boswellia, also known as frankincense, is an extract taken from the Boswellia serrata tree. Boswellia reduces inflammation by blocking the production of inflammatory compounds, similar to how corticosteroids act (blocking 5-lipoxygenase). Boswellia has been used in traditional medicine to treat a wide range of disease, particularly in people suffering from chronic inflammation [R, R].
In a meta-analysis of 260 patients with rheumatoid arthritis, 400 mg of boswellia extract reduced swelling, pain, and stiffness. Patients were also able to reduce painkiller (NSAIDs) intake while taking boswellia and required fewer emergency treatments [R].
In a study of bronchial asthma (double-blind randomized controlled trial), 70% of patients showed improvement when taking 300 mg boswellia extract, compared to only 27% in the placebo group [R].
Boswellia supplements are made from the resin of the boswellia serrata tree. It is available as a capsule, tablet, or its bark decoction orally. It is difficult for boswellia supplements to be standardized because of differences in geographical source, harvesting conditions, and manufacturing processes [R].
2) Cat’s Claw
Cat’s claw (Uncaria tomentosa) is a vine found in tropical areas of South and Central America.
Cat’s claw reduces inflammation similar to prednisone (by reducing the activation NF-kB). Cat’s claw also blocks other inflammatory compounds (TNF-alpha and IL-1alpha, IL-1beta, IL-17, and IL-4) [R, R, R].
In rats with arthritis, cat’s claw decreased inflammation and pain [R].
The 2 most common species of cat’s claw are Uncaria guianensis and Uncaria tomentosa. Uncaria tomentosa is preferred because it is easier to standardize and has a higher alkaloid (anti-inflammatory, antiviral, antioxidant compound) content [R].
Effective dose standardization of cat’s claw supplement has been unreliable because of the differences in parts of the plant used, harvesting conditions, and lack of human dosing studies. Cat’s claw is available as capsules, extracts, tinctures, decoctions, and teas [R].
Resveratrol is a compound found in many foods, most notably in grape skins and red wine [R].
Resveratrol reduces inflammation by:
- Reducing and blocking inflammatory molecules (IL-4, IL-5, TNF-α, NF-κB, COX-2, PGE2, iNOS) [R, R, R, R]
- Increasing an anti-inflammatory molecule (IL-10) [R]
Resveratrol cannot be obtained in therapeutic doses through foods. As a supplement, it is available as a cream, tablet, capsule, and tincture [R].
Bromelain is an enzyme found in pineapple extract. Bromelain reduces inflammation by blocking inflammatory compounds during excessive inflammation (COX-2, PGE-2, IL-1beta, INF-alpha, IL-6, and TNF-alpha). However, bromelain also activates these compounds (IL-1 beta, INF-gamma, IL-6, and TNF-alpha) in a healthy immune response. This makes is an immunomodulator [R, R].
In a preliminary study of 77 patients with osteo- or rheumatoid arthritis (randomized controlled trial), 200 mg or 400 mg bromelain improved knee health and psychological well-being, but 400 mg showed greater overall symptom improvement, reduced stiffness, and improved physical function [R].
Bromelain composition varies based on the source and method of purification. Bromelain from the pineapple stem has a higher protease content compared to bromelain extracted from the pineapple fruit. Bromelain is available as a tablet, capsule, cream, liquid extract, powder, and tincture [R].
Ginger is a very complex herb with over 400 compounds. Gingerols, shogaols, and paradols have been identified as the major components responsible for ginger’s anti-inflammatory effects.
Ginger reduces inflammation by blocking:
- The production of inflammatory compounds and cells (COX-1, COX-2, 5- lipoxygenase, NF-κB, prostaglandin, and leukocytes), similar to corticosteroids like prednisone [R, R, R, R, R]
- Immune cells from arriving at the site of inflammation (reducing cytokine recruitment) [R]
However, in another study of 75 osteoarthritic patients (double-blind randomized controlled trial), 170 mg ginger extract had no benefits compared to placebo [R].
The conflicting results in human studies may be due to different types of ginger extracts used, dosing, and duration of treatment.
The proportion of gingerols, shogaols, and paradols found in ginger varies based on geographic origin, method and time of harvest, and method of preparation. Ginger supplements are available as a tea, tablet, tincture, and powder [R].
Curcumin is a component of turmeric and can be used to improve autoimmune and inflammatory diseases such as rheumatoid arthritis, lupus, and inflammatory bowel disease.
In a study of 89 patients with inactive ulcerative colitis (double-blind randomized controlled trial), 1 g of curcumin in addition to typical drugs (sulfasalazine or mesalamine) reduced relapse rates compared to placebo [R].
In a study of 45 patients with rheumatoid arthritis (single-blind randomized controlled trial), 500 mg curcumin improved tenderness, joint swelling, and disease activity more than diclofenac sodium (50 mg), or both combined [R].
In a study of 23 patients with lupus and kidney inflammation (double-blind randomized controlled trial), 500 mg turmeric 3 times per day improved kidney function (decreased blood and protein in the urine) better than placebo [R].
Curcumin is available as emulsions, tablets, capsules, powders, nanoparticles, and liposomal encapsulations. Curcumin has limited bioavailability due to poor absorption and rapid breakdown. Combining curcumin and piperine (from black pepper) can increase curcumin’s bioavailability, and many supplements contain both substances [R, R].
7) Green Tea
One of the main anti-inflammatory components of green tea is epigallocatechin-3-gallate (EGCG).
In an animal study, EGCG blocked neutrophil from traveling to the inflamed sites, blocked the formation of new blood vessels due to inflammation, and stopped lung scarring. In rats with rheumatoid arthritis, green tea extract reduced levels of an inflammatory compound (PGE2) [R, R].
EGCG blocked neutrophils in a cell study at EGCG amounts that are readily obtained by moderate green tea drinking in humans [R].
Although cell studies of EGCG herald its antioxidant and anti-inflammatory effects, the results from human studies are conflicting. The reason could be EGCG’s poor bioavailability and breakdown in the body [R].
EGCG is available as standardized green tea extract capsules, powders, or as green tea. To get the most EGCG out of your green tea, steep in 80°C water for 5-15 min [R].
Limitations and Caveats
The studies that mention the side effects of prednisone have a small sample size or are uncontrolled. More clinical studies are required in order to gain a better understanding of whether the benefits of prednisone use outweigh the risk of adverse events.
The general consensus regarding the natural alternatives discussed above is that although cell and animal studies show promising results, there are very few controlled, clinical trials about the beneficial effects of these natural alternatives in humans. Further research on bioavailability, effectiveness, dosing, and adverse side effects in humans would provide more insight.
Genetics Related to Prednisone
Prednisone must be converted by prednisolone by the liver before it becomes active. Therefore, liver disease may decrease prednisone metabolism and its anti-inflammatory effects [R].
Mutations in the NR3C1 gene, which encodes the glucocorticoid receptor, may also affect response to prednisone treatment. Depending on the nature of the mutation, it may increase or decrease the sensitivity of glucocorticoids like prednisone [R].
Since inflammation and the effects of prednisone are influenced by your genes. If you’ve gotten your genes sequenced, SelfDecode can help you determine if you are more prone to inflammation as a result of your genes, and then pinpoint what you can do about it.
If you’re sick and tired of guessing about your health, SelfDecode can help you find specific answers that conventional doctors/diagnostics may never uncover.
User Experiences with Natural Alternatives
- 262 mg of boswellia supplement reduced pain and swelling in hands.
- Taking boswellia with turmeric reduced arthritic pain with no side effects.
- 485 mg of cat’s claw supplement was comparable to taking minocycline for rheumatoid arthritis in relieving pain.
- 500 mg of cat’s claw used in combination with iodoral reduced severe brain inflammation.
- Resveratrol improved colon bleeding and inflammation.
- One user reported severe dizziness when taking resveratrol.
- One user combines resveratrol and ginger for reducing inflammation.
- A 67-year-old woman with ulcerative proctitis reported improvement in bowel movement without blood or urgency by taking 2 tablets/day bromelain.
- Taking 500 mg bromelain twice a day before meals improved digestion and inflammation.
- Taking 500 mg bromelain 1-3 times a day on an empty stomach improved inflammation and joint pain without any of the side effects associated with NSAIDs or acetaminophen.
- Multiple users report that ginger root extract was useful in treating inflammation and digestive problems such as nausea.
- Ginger tea was effective in reducing anxiety, improving digestion, and decreasing inflammation.
- Users report that supplements labeled as “ turmeric root powder” only contained a low percentage of curcumin.
- A standardized turmeric supplement that contains 95% curcumin was effective in relieving joint pain and inflammation.
Green Tea (EGCG)