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Melatonin and Prednisone – Is it Safe?

Melatonin and Prednisone – Is it Safe?

Can I Take Melatonin with Prednisone?

The short answer is YES.

You can take melatonin with prednisone.

There’s a controversial myth floating around the internet to be aware of that’s not supported by scientific evidence.

Many Prednisone Warriors, searching for ways to counteract side effects like insomnia, have a hard time finding accurate information.

One recently wrote, asking me this question about melatonin and prednisone:

“Because I read widely over many websites regarding my condition, I was quite dismayed to come across a posting from the Mount Sinai Hospital yesterday evening which indicates that Melatonin is actually contradicted for corticosteroid treatment. This view is echoed around the web, with some websites even saying it can interfere with corticosteroids and cause this treatment to be less effective. Could I kindly ask about your take on this?”

Watch now!

Melatonin-Prednisone Drug Interaction Myth

This is a controversial topic.

The drug interaction/statement on their website about melatonin and corticosteroids is not backed up by evidence.

Definitely discuss with your doctor.

But just know that there is no great evidence supporting that drug interaction claim on Mt. Sinai’s website.

There’s no great evidence that melatonin actually causes treatment to be less effective.

Looking through the cited literature in their article, not one of them actually establishes that fact.

It appears, like many other steroid/prednisone/prednisolone “facts” that someone wrote it once a long time ago and others just copied/pasted it into their articles.

But there’s not great evidence supporting it.

Half of drug interaction sites show that there is no interaction between melatonin and prednisone.

Can you take melatonin with prednisone?

Can Melatonin Support Prednisone?

Instead, there are other articles that show melatonin along with steroids can actually improve treatment:

Multiple sclerosis:

“[Steroid] therapy for 1 or 2 days resulted in a significant reduction of melatonin serum levels in MS patients.


Since corticosteroids cause a reduction in melatonin serum levels, an important hormone in sleep regulation, their prescription to MS patients should be carefully considered.

Corticosteroids could be a cause of insomnia and sleep disturbance in patients receiving this type of medication.

In addition, we demonstrated, for the first time, a correlation between serum levels of melatonin and [steroid] treatment.”


“Melatonin was given orally at 20 mg/day in the evening for 2 months.

No Melatonin-related toxicity occurred.

A normalization of platelet number was achieved in 8/14 (57%), and platelet mean number significantly increased on Melatonin therapy.

This preliminary study would suggest that Melatonin may be effective in the treatment of thrombocytopenia due to different reasons, for which no effective standard therapy is available.”

ICU Critically Ill

“Given the known depletion of serum melatonin levels, melatonin supplements are an attractive and relatively safe option for steroid-induced insomnia.”

Cortisol Prednisone Melatonin Sleep Disruption Delirium
Mechanisms for Steroid-Induced Sleep Disruption and Delirium. From the ICU Study by Cole, et al.


“It has been reported that dexamethasone-induced ECM degradation in chondrocytes in a dose-dependent manner and reduced the intracellular proportion of nicotinamide adenine dinucleotide (NAD)+/NAD + hydrogen (NADH) and the supernatant concentration of NADP/NADPH. Melatonin pre-treatment can reverse these negative effects, possibly via the NAD+-dependent activation of SIRT1 (105).”

What Prednisone Side Effects Can Melatonin Support?

The ICU study, above, shows that melatonin can help with the behavioral changes, mood changes, delirium, etc. from steroids like prednisone.

Another study focused on melatonin and wondered: if melatonin is combined with other micronutrients, could it help with osteoporosis?

  • Osteoporosis: “These findings provide both clinical and mechanistic support for the use of MSDK [Melatonin, Strontium, Vitamin D, & Vitamin K] for the prevention or treatment of osteopenia, osteoporosis or other bone-related diseases.”

How Does Prednisone Cause Insomnia?

Prednisone mimics a naturally occurring hormone in our bodies called cortisol.

1. Normal Circadian Rhythm

Normally, cortisol is high in the morning when we wake up, and then drops throughout the day.

Its opposite hormone, melatonin, causes drowsiness and helps us sleep at night.

When one goes high, the other goes low, in a dance throughout the day and night.

This is called the Circadian Rhythm.

It helps us wake up and fall asleep at the right times, as we are spinning around the sun.

Normal Circadian Rhythm
Normal Circadian Rhythm for Cortisol and Melatonin

2. Prednisone Disrupting Circadian Rhythm

When people take prednisone, it artificially increases the “cortisol” in the body.

That makes the melatonin lower than normal.

Prednisone disrupts the circadian rhythm.

Prednisone Disrupting Circadian Rhythm
Prednisone Disrupting the Circadian Rhythm for Cortisol and Melatonin

Does Prednisone Deplete Melatonin?

Yes, prednisone depletes melatonin.

Circadian Rhythm is disrupted even by just one dose of corticosteroids.

One study of healthy young males taking one dose showed that “the clearly visible circadian rhythm prior to treatment was almost completely suppressed and deregulated by dexamethasone.”

This shows that prednisone, dexamethasone, or other corticosteroids in doses higher than normally made by the body, can cause insomnia.

No wonder insomnia is the #1 tweeted side effect of prednisone!

Dozens of memes, like the one below, have been created by desperate Prednisone Warriors struggling with sleeplessness.

prednisone insomnia meme

Nutranize Zone Contains Melatonin

I invented Nutranize Zone, the first and only supplement designed for people on prednisone.

Melatonin topped the list of ingredients I intentionally included to counteract how prednisone depletes it.

I included it in my special Bedtime blend of vitamins and herbs. Just two capsules at bedtime can help support restful sleep.

Nutranize Zone

Dr. Megan Milne, PharmD, BCACP

Dr. Megan Milne, PharmD, BCACP, is an award-winning clinical pharmacist board certified in the types of conditions people take prednisone for. Dr. Megan had to take prednisone herself for an autoimmune condition so understands what it feels like to suffer prednisone side effects and made it her mission to counteract them as the Prednisone Pharmacist.

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