Evidence Based
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Methylprednisolone Uses, Side Effects & Natural Options

Written by Mathew Eng, PharmD | Reviewed by Ana Aleksic, MSc (Pharmacy) | Last updated:
Jonathan Ritter
Medically reviewed by
Jonathan Ritter, PharmD, PhD (Pharmacology) | Written by Mathew Eng, PharmD | Reviewed by Ana Aleksic, MSc (Pharmacy) | Last updated:

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Achilles Tendinitis, Injury after exercising and running. Need to see doctor for treatment
Methylprednisolone belongs to a class of synthetic anti-inflammatory drugs called corticosteroids. It changes the body’s immune response and is commonly used to treat arthritis. However, long-term use and high doses can cause serious side effects. Keep reading to learn about this drug and best natural anti-inflammatories.

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 scientific and clinical literature. Please discuss your medications with your doctor.

What Is Methylprednisolone?

Methylprednisolone (brand names: Medrol, Depo-Medrol, Solu-Medrol) is a corticosteroid used to reduce inflammation or immune response in various conditions, including [1]:

It is also available as a generic medication. It is taken either in tablet form (2mg, 4mg, 8mg, 16mg, 32mg) or as injections into a vein or muscle.

The Food and Drug Administration (FDA) approved its use in 1957. Methylprednisolone is listed on the WHO List of Essential Medicines [2].

Comparison to Other Corticosteroids

Methylprednisolone is the standard corticosteroid drug in Europe, while in the US it is prednisone (Deltasone). The main difference between these drugs is that methylprednisolone is also available as injections.

Some other corticosteroid drugs are [3]:

  • Dexamethasone (Dexamethasone Intensol)
  • Prednisolone (Orapred, Prelone)
  • Betamethasone (Celestone)
  • Hydrocortisone (Cortef)
  • Triamcinolone (Aristocort, Kenalog)

The choice of corticosteroid drug depends on how you are advised to take the drug and how effective it is for the specific disease/disorder you are suffering from.

Mechanism of Action

Methylprednisolone mimics the function of glucocorticoid steroid hormones that the body produces, such as cortisol.

The body has receptors for cortisol in almost every cell in the body. This reduces inflammation by [4, 5]:

  • Blocking the production and release of compounds (prostaglandins) that cause inflammation and pain [6, 7].
  • Increasing the production of anti-inflammatory compounds (cytokine IL-10).
  • Blocking the production of pro-inflammatory compounds (cytokines IFN-γ, TNF-α, and IL-2).
  • Blocking the activation of immune cells (T-cells), which trigger inflammation.
  • Decreasing the damage from high amounts of nitric oxide and tumor necrosis factor alpha (TNF-α).
  • Increasing cell death of activated immune cells.

Methylprednisolone may also reduce the breakdown of myelin (by decreasing calpain), which could be helpful for multiple sclerosis [8].

Uses of Methylprednisolone

1) Rheumatoid Arthritis

Rheumatoid arthritis is a chronic inflammatory disease of the joints.

Methylprednisolone injection reduces pain and improves physical function in knee osteoarthritis. Multiple studies have shown that methylprednisolone injection greatly decreased pain, stiffness, and improved function in knee osteoarthritis [9, 10, 11, 12].

In one study on 83 rheumatoid arthritis patients, methylprednisolone injection with a local anesthetic (bupivacaine) reduced shoulder pain and improved shoulder movement [13].

In another study on 44 rheumatoid arthritis patients, treatment with intravenous methylprednisolone and an anti-rheumatic drug (methotrexate) reduced arthritis symptoms in 70% of patients [14].

A third study on 10 rheumatoid arthritis patients, intravenous methylprednisolone pulse therapy was given every month for 6-months. Patients treated with methylprednisolone could walk faster, grip things with their hands, and felt pain relief from inflamed joints. However, methylprednisolone did not delay the progression of arthritis [15].

Methylprednisolone pulse therapy improved symptoms of arthritis in children and adolescents (juvenile idiopathic arthritis) [16, 17].

Intravenous methylprednisolone decreased the blood levels of proteins involved in inflammation (C-reactive protein, IgG, and IgA) in 14 patients with severe rheumatoid arthritis. Three patients showed remarkable improvements in arthritic symptoms lasting for more than 42 weeks [18].

2) Lupus

Lupus occurs when someone’s immune system attacks healthy cells in the body for reasons mostly unknown. Since methylprednisolone reduces the immune system’s response, it may lessen the severity of lupus symptoms.

Intravenous methylprednisolone suppressed the immune system in the initial stages of lupus in a small study on 25 patients [19].

In a study on 82 patients with inflamed kidneys caused by lupus (lupus nephritis), combination therapy of methylprednisolone and an immunosuppressive drug (cyclophosphamide) greatly reduced inflammation of the kidneys after 1 year [20].

Methylprednisolone and an immunosuppressive drug (azathioprine) improved quality of life in a study on 47 patients with inflamed kidneys. Multiple studies in children with the same condition have shown that methylprednisolone was also effective in improving kidney function [21, 22, 23].

However, the standard dose of methylprednisolone used for lupus (1 g/day for 3 consecutive days) may lead to infections. Lower doses (≤ 1500 mg/day) are still effective in improving symptoms of lupus [24, 25].

3) Sarcoidosis

Sarcoidosis is a disease with an unknown cause in which white blood cells form lumps in various organs including the lungs, lymph nodes, and skin [26].

In a study of 12 patients with sarcoidosis, high-dose intravenous methylprednisolone quickly improved symptoms when given weekly for 6 weeks. However, 8 of the 12 patients relapsed after a year and required additional treatment [27].

Methylprednisolone improved lung function in 39 patients with stage 2 lung sarcoidosis, but the improvements were not different from the untreated patients after 2-4 years. It also reversed the progression of sarcoidosis in the lungs in 24 patients with pulmonary sarcoidosis [28, 29].

Multiple case reports have shown that methylprednisolone is effective in managing sarcoidosis of various body parts, such as spine and pituitary gland [30, 31, 32, 33].

4) Relapse Symptoms in Multiple Sclerosis

A relapse or acute attack in multiple sclerosis (MS) occurs when disease symptoms suddenly increase in severity.

Intravenous methylprednisolone treatment improved relapse symptoms and reduced disability in MS patients in multiple studies [34, 34, 35].

In another study, methylprednisolone was better at reducing relapse symptoms rapidly than ACTH, the standard treatment for relapses in multiple sclerosis. However, its beneficial effects were similar to ACTH after 3-months, suggesting that it is an effective short-term treatment [36].

In a study on 199 MS patients, oral and intravenous methylprednisolone improved symptoms of relapse in MS after 1-month [37].

Multiple studies have shown that oral methylprednisolone is as effective as intravenous methylprednisolone in treating relapses in MS [38, 39, 40, 41].

5) Inflammatory Bowel Disease (IBD)

In Irritable Bowel Disease (IBD), the digestive tract and inner lining of the colon are acutely or chronically inflamed. The two major types of IBD are ulcerative colitis and Crohn’s disease. An acute attack can be fatal if not handled quickly and properly, due to bleeding and severe inflammation [42].

Improves Symptoms of Ulcerative Colitis

The death rates from ulcerative colitis have reduced from 30-60% before corticosteroid use to about 1 – 2.9% at present [43].

Methylprednisolone (pulsed high-dose) improved symptoms in 12 of the 20 patients with ulcerative colitis. 8 patients had to undergo surgery due to more severe disease [44].

In another study (open-label, randomized), methylprednisolone reduced symptoms of ulcerative colitis in 40 patients after 2 weeks of treatment [45].

Improves Symptoms of Crohn’s Disease

Methylprednisolone reduced symptoms of Crohn’s disease in 24 of the 33 patients treated for 8-weeks in one study [46].

In a study on 70 patients with Crohn’s disease, methylprednisolone treatment for 3-weeks abolished all symptoms (remission) in 91% of patients but, symptoms started coming back 6 months after stopping treatment [47].

6) Pain Sensitivity

Hyperalgesia refers to higher than usual sensitivity to pain. It is a result of increased levels of pro-inflammatory compounds in the body (platelet-activating factor PAF and cytokines), which produce the sensation of pain [48].

In one study, 12 healthy participants were subjected to a burn injury on their abdomen before being given either methylprednisolone, ketorolac (a non-steroidal anti-inflammatory drug), or placebo. Methylprednisolone increased pain tolerance, but less than ketorolac [49].

Methylprednisolone prevented hyperalgesia from nerve injuries in mice [50].

7) Asthma Attacks

Corticosteroids are often used to reduce inflammation in asthma. But, methylprednisolone is not available as inhaled medication and is only used in emergency situations.

In a study on 99 asthma patients who had an emergency attack, intravenous methylprednisolone was given along with the standard treatment for asthma. Methylprednisolone reduced the need for hospital admission to 19% of patients, compared to 47% of patients not given the methylprednisolone [51].

Methylprednisolone injections into the muscle reduced asthma attacks from coming back in 70 patients with acute asthma in a study [52].

In another study of 28 children with asthma, short-term methylprednisolone treatment (8-days) resolved symptoms of acute asthma attacks [53].

8) Skin Conditions

Methylprednisolone is applied on the skin for many conditions related to inflammation or allergies, such as [54]:

  • Itching
  • Burning
  • Pain
  • Erythema (rash)
  • Edema
  • Eczema (including Atopic Dermatitis) [55, 54]
  • Psoriasis [54]

In a study of 221 patients with atopic dermatitis, application of methylprednisolone combined with a moisturizer (Advabase) twice weekly reduced the risk of relapse, itching intensity, and improved overall skin health [56].

In a study of 16 eczema patients, methylprednisolone cream provided rapid itch relief when applied for 5-days [57].

Methylprednisolone ointment application for 11-days improved psoriasis symptoms in a study on 14 patients [58].

9) Pain in Bursitis

Bursitis is the painful inflammation of fluid-filled cavities in the joints in the body, including knees, shoulders, elbows, and hips [59].

Injection of methylprednisolone and an anesthetic (lidocaine) provided pain relief in 65 out of 72 patients with bursitis of the hip joint [60].

10) Quality of Life in Cancer Patients

Methylprednisolone increased appetite, activity level, decreased depressive symptoms, and the need for painkillers in 40 terminally ill cancer patients in one study [61].

In another study of 47 cancer patients, methylprednisolone improved appetite, fatigue, and overall patient satisfaction [62].

11) Rejection of Organ Transplants

Rejection of a transplanted organ can happen if the immune system recognizes them as foreign. Drugs are used to reduce the immune response for a short time until the organ and body adjust. A combination of drugs is typically used (methylprednisolone, cyclosporine, and azathioprine) to triple the effect [63].

Intravenous methylprednisolone alone resolved the rejection of a liver transplant of 38 patients in one study [64].

12) Thyroid Eye Disease

Thyroid eye disease is an autoimmune disease in which immune cells attack the back of the eye, resulting in eye swelling, redness, and sometimes decreased vision [65].

In a study of 376 patients with this disease, intravenous methylprednisolone (pulse therapy) was more effective than oral tablets as it reduced eye swelling before vision loss occurs [66].

Two studies on 70 and 52 patients with severe thyroid eye disease, intravenous methylprednisolone was well-tolerated and improved disease symptoms better, quicker, and longer-lasting than oral methylprednisolone [67, 68].

13) Hair Loss and Baldness

Alopecia is an autoimmune disease in which hair is lost from the scalp in patches that can progress to total loss of scalp hair and total loss of body hair [69].

Multiple studies have shown that methylprednisolone (pulse therapy) was well-tolerated and reduced hair loss and increased hair regrowth in patients with alopecia [70, 71, 72, 73, 74, 75, 76].

Methylprednisolone Side Effects

Side effects from methylprednisolone can range from mild to severe depending on dosage and the way it’s taken (injections or pills), including:

  • Increased appetite
  • Weight gain around the neck, upper back, chest, waist, wrist, or ankles
  • More serious side effects include:
  • Slow wound healing
  • Swelling of fingers, hands, or feet
  • Nausea and vomiting
  • Dizziness
  • Fatigue
  • Headaches
  • Stomach pain
  • Bloating
  • Depression, mood changes
  • Aggression/agitation
  • Blurred vision
  • Pounding in the ears
  • Irregular heartbeat
  • Anxiety/nervousness
  • Tingling sensation in arms or legs
  • Itching, hives, swollen throat, shortness of breath (signs of allergic reaction)

Rapid, high doses of methylprednisolone can have adverse effects, such as:

  • Hypertension
  • Irregular heartbeat
  • Psychosis
  • Infections

Contraindications

Methylprednisolone is contraindicated in [77, 78, 79, 80]:

  • Hypersensitivity to methylprednisolone or any other ingredient
  • Serious yeast infections
  • Excessive bruising and bleeding due to low platelets (a condition known as Idiopathic thrombocytopenic purpura) for muscle injections.
  • Patients receiving vaccines such as the chickenpox, and measles, mumps, and rubella (MMR) vaccine (which contain the whole virus, live or deactivated).
  • Premature infants (since the formulations contain benzyl alcohol).
  • Pregnancy
  • Patients with herpes simplex of the eye
  • As injections into the spinal cord

Drug Interactions

Methylprednisolone interacts with many drugs, such as [77, 78, 79, 80]:

  • Antibiotics (troleandomycin, erythromycin, isoniazid, rifampin, clarithromycin, erythromycin)
  • Antifungals (ketoconazole, itraconazole)
  • Antivirals (indinavir, ritonavir)
  • Muscle relaxants used for anesthesia (pancuronium, neuromuscular blockers)
  • Drugs used for extreme muscle weakness (neostigmine, pyridostigmine)
  • Anticoagulants (aspirin, warfarin, heparin)
  • Anti-seizure drugs (phenobarbital, phenytoin, carbamazepine)
  • Drugs used to lower blood sugar in diabetes (insulin, glibenclamide, metformin)
  • Other drugs that reduce immune response (cyclosporine, cyclophosphamide, tacrolimus)
  • Drugs used to reduce nausea (aprepitant, fosaprepitant)
  • Drugs that reduce cholesterol or laxatives (cholestyramine)
  • Blood pressure lowering drugs
  • Antisteroid drug (aminoglutethimide)
  • Anti-anxiety and antipsychotic drugs
  • Hormones, such as estrogens in oral contraceptives (ethinylestradiol)
  • Drugs used for heart conditions (digoxin, diltiazem)
  • Diuretics (furosemide)

Methylprednisolone Dosage and Forms

The dosage, form of the drug, and how often it should be taken will depend on various factors, such as age, disease/disorder, severity, reaction to first drug dose, and other existing medical conditions.

Methylprednisolone can be taken orally or injected into vein or muscle in the following doses [77, 78, 79, 80]:

  • Oral: 2 mg, 4 mg, 8 mg, 16 mg, 32 mg, 48 mg
  • Intramuscular injection (per mL): 20 mg, 40 mg, 80 mg
  • Intravenous injection (per mL): 40 mg, 125 mg, 500 mg, 1 g, 2 g

It is also available as a cream/ointment.

Medrol Dose Pack

Methylprednisolone is commonly prescribed as a blister pack, sometimes called a Medrol Dose Pack (Dosepak). They are typically used to provide immediate, short-term inflammation control.

These packs are specially designed to show how many tablets to take each day and when to take them. Packs contain a total of 21 tablets, with each tablet being 4 mg [81].

The standard dosing regimen is [81]:

  • Day One: 2 before breakfast, 1 after lunch, 1 after dinner, 2 at bedtime (6 total)
  • Day Two: 1 before breakfast, 1 after lunch, 1 after dinner, 2 at bedtime (5 total)
  • Day Three: 1 before breakfast, 1 after lunch, 1 after dinner, 1 at bedtime (4 total)
  • Day Four: 1 before breakfast, 1 after lunch, 1 at bedtime (3 total)
  • Day Five: 1 before breakfast, 1 at bedtime (2 total)
  • Day Six: 1 before breakfast (1 total)

Why do this? This kind of dosing strategy is called a taper, where the dose starts high and is gradually decreased. This ensures an immediate reduction of inflammation while minimizing withdrawal effects [82].

It’s important to take methylprednisolone exactly how it was prescribed by your doctor. If side effects occur or if there is an issue that stops you from taking the drug, you should talk to your doctor immediately.

Pulse Therapy

  • Pulse therapy involves giving high doses of methylprednisolone under careful supervision when the patient needs quick or effective action to suppress the immune system such as in [83, 84]:
  • Lupus
  • Skin disease (pemphigus)
  • Kidney Transplants
  • Kidney damage (nephrotic syndrome)

Limitations and Caveats

The long-term effects of methylprednisolone on the body are not well-known, especially for children and adolescents.

Since methylprednisolone reduces the immune response, it may hypothetically increase the risk of cancer. But the potential of methylprednisolone to increase this risk has not been evaluated yet.

Hence, it should be used cautiously under medical supervision.

Natural Options

There are a number of plant-derived compounds that have an anti-inflammatory effect.

The natural alternatives listed here share many of the same mechanisms as methylprednisolone, such as blocking prostaglandins, leukotrienes, and NF-κB [85, 86].

Do not stop taking methylprednisolone without talking to your doctor first. Serious side effects can occur if the drug is abruptly stopped.

It’s also important to let your doctor know of all the supplements you are currently taking, in case of potential interactions.

1) Ginger

Inside ginger are many active compounds that have anti-inflammatory effects, such as gingerols, shogaols, and zingerone [87].

These compounds can block inflammatory compounds like COX-1, COX-2, 5-lipoxygenase, NF-κB, and leukocytes, similar to methylprednisolone [88, 89].

A review of 5 clinical trials totaling 593 patients found that ginger is safe and modestly effective for osteoarthritis [90].

A different review of 7 studies shows that it reduces pain from resistance exercise and prolonged running [91].

In yet another review of 7 clinical trials, ginger effectively reduced the pain caused by menstrual cramps [92].

However, the majority of these studies are fairly small. All of these reviews state that larger clinical trials are needed to better evaluate ginger’s effectiveness [92, 91, 90].

2) Fish Oil

Fish oils contain two major active components: DHA and EPA, which are both omega-3 fatty acids [93].

These compounds can reduce levels of prostaglandins, TNF-α, and NF-κB, much like methylprednisolone [94, 95, 96].

One study of 250 people found that 60% of those taking fish oil report overall pain improvement [97]

On top of that, 59% of people stopped taking their prescription NSAIDs and 88% said they would continue taking fish oil [97].

Fish oil is also effective for rheumatoid arthritis, but not for osteoarthritis, according to a review of 42 clinical trials [98].

Other clinical trials suggest that fish oil may help with menstrual cramps and diabetic neuropathy [99, 100].

3) Boswellia

The Boswellia tree produces a special resin (called frankincense) that may help reduce inflammation [101].

Some of the compounds inside Boswellia can block 5-lipoxygenase, which prevents the release of leukotrienes. This mechanism is also seen in corticosteroids like methylprednisolone [101, 85].

Boswellia extract improves short-term pain and physical function in people with osteoarthritis of the hand, hip or knee. This is according to a large review of 69 studies that examined the effects of 20 different supplements [102].

According to a study of 32 asthmatic patients, extracts may reduce the need for inhalers [103].

Other studies suggest it may also help in rheumatoid arthritis, ulcerative colitis, and Crohn’s disease [104].

4) Cat’s Claw

Cat’s claw (Uncaria tomentosa) is a thick vine that is indigenous to tropical areas of South and Central America [105].

Similar to methylprednisolone, cat’s claw reduces the activation of NF-κB. It also blocks other inflammatory compounds like TNF-α, IL-1, and IL-4 [106, 107, 105].

Cat’s claw reduces pain associated with osteoarthritis of the knee, according to a study of 45 people. No side effects were reported and no harmful effects on the liver or blood were detected [108].

A different study of 40 people with rheumatoid arthritis found that cat’s claw extract reduces the number of painful joints [109].

Be careful when buying supplements. Cat’s claw can be sourced from two different species of plant: Uncaria guianensis and Uncaria tomentosa. The latter is typically preferred because it has higher anti-inflammatory and antioxidant activity [105].

5) Resveratrol

Resveratrol is a natural compound found in many foods, including berries, peanuts, and red wine [110].

It works by blocking a number of inflammatory compounds, such as NF-κB, TNF-α, COX-2, and PGE2 [111, 112].

In a study of 110 patients suffering from knee osteoarthritis, resveratrol was shown to improve pain and physical function [113].

Resveratrol also improves chronic pain related to menopause, according to a study of 80 women [114].

Animal studies show that it may help with bone cancer pain, neuropathic pain, and inflammatory bowel disease [115, 116, 117].

6) Curcumin

Curcumin is one of the major active compounds found inside turmeric. It also has an anti-inflammatory effect, thanks to its ability to regulate TNF-α, IFN-gamma, and NF-κB [118].

A review of 8 clinical trials found that curcumin reduces arthritis pain [119].

Curcumin supplements may also reduce post-exercise muscle soreness, according to a small study of 17 people [120].

In a different study of 90 patients, it reduced post-surgery pain caused by removal of impacted molars [121].

Based on research done in animals, curcumin may also slow osteoarthritis progression and reduce neuropathic pain [122, 123].

Want More Targeted Ways to Combat Inflammation?

If you’re interested in natural and more targeted ways of lowering your inflammation, we at SelfHacked recommend checking out this inflammation wellness report. It gives genetic-based diet, lifestyle and supplement tips that can help reduce inflammation levels. The recommendations are personalized based on your genes.

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About the Author

Mathew Eng

Mathew Eng

PharmD
Mathew received his PharmD from the University of Hawaii and an undergraduate degree in Biology from the University of Washington.
Mathew is a licensed pharmacist with clinical experience in oncology, infectious disease, and diabetes management. He has a passion for personalized patient care and believes that education is essential to living a healthy life. His goal is to motivate individuals to find ways to manage their chronic conditions.

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