12-week melatonin intake attenuates cardiac autonomic dysfunction and oxidative stress in multiple sclerosis patients: a RCT, 2024, Jallouli

https://link.springer.com/article/10.1007/s11011-024-01428-2

12-week melatonin intake attenuates cardiac autonomic dysfunction and oxidative stress in multiple sclerosis patients: a randomized controlled trial

• Research
• Published: 04 December 2024

Abstract

Multiple sclerosis (MS) can induce cardiac autonomic dysfunction identified by a decreased heart rate variability (HRV) which was linked to oxidative stress, vitamin D deficiency and sleep disturbance.

Previous MS studies revealed the antioxidant and anti-inflammatory effects of exogenous melatonin, as well as its benefits on sleep and vitamin D.

We aimed to investigate the change in HRV, oxidative stress, systemic inflammation and sleep following melatonin supplementation in MS patients.

Participants were randomly allocated to either a melatonin group (MG, n = 15) or a placebo group (PG, n = 12) (3 mg/night during 12 weeks).

Pre- and post-tests included HRV analysis (Kubios software), sleep dairy and biological analysis [oxidative stress biomarkers (malondialdehyde (MDA), advanced oxidation protein products (AOPP) and reduced glutathione (GSH)); 25-hydroxyvitamin D; C-reactive protein and cholinesterase Gen.2 (CHE2)].

Based on the pre-post supplementation change (Δ (T1₋T0)), melatonin increased the root mean square of successive differences between normal heartbeats [ΔMG (14.17 ± 16.93) vs. ΔPG (₋8.61 ± 12.67), p = 0.0007] and the HRV high-frequency band [ΔMG (6.86 ± 14.85) vs. ΔPG (₋12.58 ± 13.30), p = 0.0016] comparatively with placebo. MG showed a decrease in the HRV low-frequency band [ΔMG (₋4.96 ± 10.08) vs. ΔPG (10.22 ± 13.54), p = 0.003] as well as in the MDA [ΔMG (₋2.27 ± 1.92) vs. ΔPG (0.22 ± 2.30), p = 0.005] and AOPP levels [ΔMG (₋113.97 ± 137.72) vs. ΔPG (156.46 ± 230.52), p = 0.0008] compared with PG.

Melatonin enhanced the GSH [ΔMG (10.51 ± 14.93) vs. ΔPG (₋5.05 ± 10.18), p = 0.004] and CHE2 levels [ΔMG (407.07 ± 723.26) vs. ΔPG (₋22.92 ± 506.52), p = 0.029] as well as sleep quality [scores: ΔMG (1.50 ± 1.28) vs. ΔPG (₋1.05 ± 2.05), p = 0.0006] and quantity [weighted total sleep time: ΔMG (0.74 ± 1.14) vs. ΔPG (₋1.04 ± 1.00), p = 0.0003] comparatively with placebo.

Caregivers may recommend 12-week nocturnal melatonin intake to attenuate cardiac autonomic dysfunction, oxidative stress and sleep disorders in MS patients.

Clinical registration This study was prospectively registered in the Pan African Clinical Trial Registry database (PACTR202007465309582) on 23 July 2020 (https://pactr.samrc.ac.za/.).

Graphical abstract

Highlights
• 12-week melatonin supplementation (3 mg per night) alleviated cardiac autonomic dysfunction (i.e., it increased heart rate variability) in multiple sclerosis patients.

• Exogenous melatonin had benefits on oxidative stress biomarkers (reduced glutathione, malondialdehyde and advanced oxidation protein products).

• Chronic nocturnal melatonin intake enhanced sleep quality, efficiency and quantity.

 

as a side note I was intrigued years ago when I looked into it and realised there seemed to be big differences in availability/access to melatonin. In the UK I think maybe children or the elderly might be able to be prescribed it more, but for 'adults' it is never suggested and got the impression that (putting aside ME/CFS where I'm not sure it has been listed for that) it would require a specialist and even then to be prescribed with strong reasons and have a management plan beyond just sending someone back to the GP with it listed etc.

I'm not completely sure why this is the case.

and yet I get the impression this isn't the case in other countries and in some it is more freely available and I guess tried more often for that reason.

 

Circadin (prescription melatonin) is something i've been keen to get off after being prescribed it post sleep study, maybe 6 years ago - at the time Neurology stuck to guidelines and suggested I come off it after a few months but the GP hasn't blinked.

I don't need it to initiate/maintain sleep anymore now that I'm pacing better and my wider issues (POTS/AS) are treated. If I really overdo it or flare i'm going to have a disrupted night regardless. I had wondered if part of my increased orthostatic intolerance in the AM might be due to the melatonin, and with the lack of data on long-term effects I figured i'd be safer coming off and started that process a week ago.

Subjectively my sleep hasn't been much worse, but boy did I forget how much daytime lower leg pain I experience without taking melatonin. Have no idea if there's some direct explanation for that or if its simply because I'm having worse quality sleep. Either way I will probably just go back on melatonin, otherwise I think i'd need to start chronic pain meds to manage it instead and that seems like a bad deal.

 

Do you think there is something of the same fallacy you see with people these days (which is strange/due to marketing into the culture because it wasn’t this way in the past) assuming therapist-based can’t harm and doesn’t need yellow card , even when it’s CBT that is pretty combative and targeting ‘thoughts’ without proof either the one they are replacing is wrong or the change will help, or pushing through on an illness watching people get worse long term.

ie that combo of it ‘not adding in some chemical the body doesn’t already have’ fallacy (as melatonin is produced in body) just like people tend to give vitamins more leeway (although interestingly they rarely think that with steroids even if some ‘are close to those produced naturally’) or will use eg skincare ‘based in natural ingredients’ that might be actually as likely to cause allergies or issues but you see it coming less ‘because it’s natural’

and… the obsession with ‘training people to behave right’ rather than seeing it as a symptom (or maybe even not wrong just not what society wants - I’ve seen a few videos on neurodiversity that make this point on the ‘tyranny/fallacy of normal’ which is of course different to healthy or able to be useful or productive (just not under the conditions society wants to base things round)?

I ASSUME for trials melatonin would come under drugs licensing eg yellow card and side effects

but .. all I know about sleep research is a grim feeling it doesn’t move on from assuming it’s all about sleep hygiene. And it hasn’t expanded its knowledge. And I think it tends to separate off sleep from the rest of the body and the rest of someone’s health in a weird way. Unless it’s doing crap correlations about shift workers getting more illness (when how much if that is societal eg not making life easy at all in so many ways if you aren’t 9-5, like cafes being closed during shifts, often less staff and then these days imagine trying to sleep at home whilst everyone is doing building work or other noisy things - not to mention the shifts where people do different times of different days).

 

@Ryan31337 You can buy melatonin from an American online store like iHerb and get it delivered to the UK without prescription.

 

My own experience over the years, from having tried it (via iHerb) at different doses for periods of weeks and months at a time, is that it hasn't helped my insomnia at all. I won't be taking it again because of the potential risks.
I know nothing about biochemistry but it seems to me that for a hormone that is produced by the body at around 30 to 80 micrograms per day in an adult (depending on which article you read), the quantities in supplements are extreme. Because it's a supplement, proper safety studies haven't been done as far as I'm aware (?).

 

Thanks - all the time I can get prescription circadin I think that's the better option. The sleep clinic Neurologist said the supplement versions are less likely to be controlled and reliable doses.

@oldtimer clinical trials for Circadin (prescription melatonin) were done and it is approved for use in the NHS. But the trials were fairly limited so recommendations are patchy for certain age groups and not beyond 13 weeks use. I have seen a couple of literature reviews suggesting it seems safe and non-habit forming but no robust research on long-term use has be done.