When it is dark, your body release melatonin which triggers a cytokine release reaction causing inflammation in your body. That is why pain and stiffness peaks at around 4-8am.
I have GCA and PMR. I was on a daily dose of prednisone higher than 40 mg per day for 12 weeks last year. I had really bad insomnia during that time, so I took 5 mg of time released melatonin. It helped me get more sleep, and didn't seem to do any harm, other than making me feel groggy during the day. But I was feeling groggy anyway from the insomnia. Once I got down to 40 mg per day I started sleeping ok.
A study of circadian variation in PMR found that plasma concentrations of IL-6, IL-8, TNF-α, and IL-4 peaked between 4 and 8 am in both untreated patients and controls, although levels of those cytokines were higher throughout the day in patients. The peak in cytokines matched the early-morning peak of pain and stiffness in untreated patients. In addition, melatonin levels were consistently higher in patients than in controls and varied with time, peaking around 2 am, suggesting that melatonin stimulates cytokine production, which in turn accounts at least partly for PMR symptoms. [14]
A study of circadian variation in PMR found that plasma concentrations of IL-6, IL-8, TNF-α, and IL-4 peaked between 4 and 8 am in both untreated patients and controls, although levels of those cytokines were higher throughout the day in patients. The peak in cytokines matched the early-morning peak of pain and stiffness in untreated patients. In addition, melatonin levels were consistently higher in patients than in controls and varied with time, peaking around 2 am, suggesting that melatonin stimulates cytokine production, which in turn accounts at least partly for PMR symptoms. [14]
When it is dark, your body release melatonin which triggers a cytokine release reaction causing inflammation in your body. That is why pain and stiffness peaks at around 4-8am.
Melatonin is anti-inflammatory. The cytokine release is due to the lowered amount of cortisol overnight I believe. I take 2mg of Melatonin each night to help with sleep (partly because a medication I take blocks its production) and have no pain in the night or morning. My doctor who prescribes the melatonin said I should have a gap of at least two hours between taking prednisone and the melatonin.
Melatonin is anti-inflammatory. The cytokine release is due to the lowered amount of cortisol overnight I believe. I take 2mg of Melatonin each night to help with sleep (partly because a medication I take blocks its production) and have no pain in the night or morning. My doctor who prescribes the melatonin said I should have a gap of at least two hours between taking prednisone and the melatonin.
I have no opinion about melatonin but sometimes the right answer is that it depends on the circumstances. I used Benadryl (diphenhydramine) for sleep but not so much anymore since I came off Prednisone. I'm given Benadryl and acetaminophen before my Actemra infusion but I don't think I need those medications for my infusion. The combination of Benadryl and acetaminophen helps me sleep.
"Despite these multiple anti-inflammatory mechanisms of melatonin, its role is more complex than simply one as an anti-inflammatory mediator. Prior studies have shown that melatonin’s role differs depending on the stage of inflammation. It appears to have a pro-inflammatory role in early inflammation and an anti-inflammatory role in late inflammation" https://pmc.ncbi.nlm.nih.gov/articles/PMC7979486/
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I agree with the part about cortisol but it depends on the cytokine. Cortisol normally downregulates pro-inflammatory cytokines and upregulates anti-inflammatory cytokines. Cortisol "regulates" inflammation but that is complicated too. https://pmc.ncbi.nlm.nih.gov/articles/PMC3186928/
I have no opinion about melatonin but sometimes the right answer is that it depends on the circumstances. I used Benadryl (diphenhydramine) for sleep but not so much anymore since I came off Prednisone. I'm given Benadryl and acetaminophen before my Actemra infusion but I don't think I need those medications for my infusion. The combination of Benadryl and acetaminophen helps me sleep.
"Despite these multiple anti-inflammatory mechanisms of melatonin, its role is more complex than simply one as an anti-inflammatory mediator. Prior studies have shown that melatonin’s role differs depending on the stage of inflammation. It appears to have a pro-inflammatory role in early inflammation and an anti-inflammatory role in late inflammation" https://pmc.ncbi.nlm.nih.gov/articles/PMC7979486/
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I agree with the part about cortisol but it depends on the cytokine. Cortisol normally downregulates pro-inflammatory cytokines and upregulates anti-inflammatory cytokines. Cortisol "regulates" inflammation but that is complicated too. https://pmc.ncbi.nlm.nih.gov/articles/PMC3186928/
The part immediately following what you quoted about melatonin is of interest for PMR which involves chronic inflammation:
"In the early phase of inflammation, which is necessary for healing to occur in response to an acute insult, melatonin activates proinflammatory mediators including phospholipase A2 and arachidonate 5-lipoxygenase. This activation is a transient phenomenon and extinguishes within 2–3 hours. In the late inflammation phase, which refers to chronic inflammation responsible for many disease processes, melatonin exerts anti-inflammatory effects by downregulating the aforementioned inflammatory mediators and pro-inflammatory cytokines and also by reducing oxidative stress (Radogna et al., 2010)."
The part immediately following what you quoted about melatonin is of interest for PMR which involves chronic inflammation:
"In the early phase of inflammation, which is necessary for healing to occur in response to an acute insult, melatonin activates proinflammatory mediators including phospholipase A2 and arachidonate 5-lipoxygenase. This activation is a transient phenomenon and extinguishes within 2–3 hours. In the late inflammation phase, which refers to chronic inflammation responsible for many disease processes, melatonin exerts anti-inflammatory effects by downregulating the aforementioned inflammatory mediators and pro-inflammatory cytokines and also by reducing oxidative stress (Radogna et al., 2010)."
Figuring out what foods to eat and avoid with PMR drives me crazy. I have for some time avoided processed and fried foods, sugar and red meat. Then, before prednisone, PMR caused anemia so I tried to get more iron in my diet. Then methotrexate elevated my liver enzymes so I cut back alcohol to 2 drinks a week. Then Kevzara elevated my cholesterol so no eggs or cheese and oatmeal every morning. Avoiding potatoes, tomatoes and eggplant does not make sense to me since there is only an association with inflammation, not a cause and effect, and everyone is different. I will change my diet if it allows me to stay off a medication or lessen the side effects of ones I have to take but other than that I try to follow what Michael Pollan said: " Eat real food, mostly plants, not too much".
I agree. I eat a lot of Salmon, veggies (beans, peas, and salads), fruits, etc. I avoid as much as I can white bread, sugar, red meat, and fried foods. Hard to always give up so I have some of my husband's chocolate iced coffee...bad probably. NO deli meats!!
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I did not know that. Always glad to learn something new. (To me)
I have GCA and PMR. I was on a daily dose of prednisone higher than 40 mg per day for 12 weeks last year. I had really bad insomnia during that time, so I took 5 mg of time released melatonin. It helped me get more sleep, and didn't seem to do any harm, other than making me feel groggy during the day. But I was feeling groggy anyway from the insomnia. Once I got down to 40 mg per day I started sleeping ok.
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3 ReactionsA study of circadian variation in PMR found that plasma concentrations of IL-6, IL-8, TNF-α, and IL-4 peaked between 4 and 8 am in both untreated patients and controls, although levels of those cytokines were higher throughout the day in patients. The peak in cytokines matched the early-morning peak of pain and stiffness in untreated patients. In addition, melatonin levels were consistently higher in patients than in controls and varied with time, peaking around 2 am, suggesting that melatonin stimulates cytokine production, which in turn accounts at least partly for PMR symptoms. [14]
Well many thanks for reply comments. I think I will skip the Melatonin for awhile!
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1 ReactionWow, you really know your stuff. I remember now reading something warning about the taking of melatonin.
Melatonin is anti-inflammatory. The cytokine release is due to the lowered amount of cortisol overnight I believe. I take 2mg of Melatonin each night to help with sleep (partly because a medication I take blocks its production) and have no pain in the night or morning. My doctor who prescribes the melatonin said I should have a gap of at least two hours between taking prednisone and the melatonin.
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3 ReactionsI have no opinion about melatonin but sometimes the right answer is that it depends on the circumstances. I used Benadryl (diphenhydramine) for sleep but not so much anymore since I came off Prednisone. I'm given Benadryl and acetaminophen before my Actemra infusion but I don't think I need those medications for my infusion. The combination of Benadryl and acetaminophen helps me sleep.
"Despite these multiple anti-inflammatory mechanisms of melatonin, its role is more complex than simply one as an anti-inflammatory mediator. Prior studies have shown that melatonin’s role differs depending on the stage of inflammation. It appears to have a pro-inflammatory role in early inflammation and an anti-inflammatory role in late inflammation"
https://pmc.ncbi.nlm.nih.gov/articles/PMC7979486/
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I agree with the part about cortisol but it depends on the cytokine. Cortisol normally downregulates pro-inflammatory cytokines and upregulates anti-inflammatory cytokines. Cortisol "regulates" inflammation but that is complicated too.
https://pmc.ncbi.nlm.nih.gov/articles/PMC3186928/
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2 ReactionsThe part immediately following what you quoted about melatonin is of interest for PMR which involves chronic inflammation:
"In the early phase of inflammation, which is necessary for healing to occur in response to an acute insult, melatonin activates proinflammatory mediators including phospholipase A2 and arachidonate 5-lipoxygenase. This activation is a transient phenomenon and extinguishes within 2–3 hours. In the late inflammation phase, which refers to chronic inflammation responsible for many disease processes, melatonin exerts anti-inflammatory effects by downregulating the aforementioned inflammatory mediators and pro-inflammatory cytokines and also by reducing oxidative stress (Radogna et al., 2010)."
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3 ReactionsAll I know is that I'm sleeping 100% better without Prednisone.
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3 ReactionsI agree. I eat a lot of Salmon, veggies (beans, peas, and salads), fruits, etc. I avoid as much as I can white bread, sugar, red meat, and fried foods. Hard to always give up so I have some of my husband's chocolate iced coffee...bad probably. NO deli meats!!
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