Previously we discussed how melatonin can be beneficial for people with Parkinson's disease (PwP) at a dose as low as 10 mg / day. Recent studies are confirming that Parkinson's disease (PD) is a risk factor for cardiovascular disease (CVD). The relationship is not yet fully understood, but it is now clear that CVD is something that PwP need to be aware of and should be taking steps to try and prevent CVD from starting or advancing. Obviously CVD is problematic in other health issues as well as in the general public, but I will discuss how melatonin may be able to reduce the risk of CVD in PwP as well as in people in general.
What Is Cardiovascular Disease?
CVD is a broad term that covers multiple health issues including heart disease, heart attack, stroke, heart failure, arrhythmia and heart valve problems. CVD is the leading cause of death in the U.S. so taking steps against it is a worthwhile pursuit.
The following abstract link gives some insight into some of the known risk factors for CVD other than PD and further discusses how melatonin may be useful in working against these risk factors and against CVD itself.
The following meta analyses discusses how PwP are at higher risk for CVD even though it was previously speculated that PwP were at lower risk because they present with fewer vascular risk factors for CVD and smoke less. Smoking is a risk factor for CVD. If your doctor, neurologist, movement disorder specialist or other healthcare professional has not informed you of this risk factor for CVD, now you know and can take steps to try and prevent or lessen your chances for getting CVD.
In the study links below, the value of melatonin in CVD will be discussed. Melatonin has multiple positive health effects that show the potential to ameliorate some of the health issues associated with CVD. Melatonin is itself a potent scavenger of reactive oxygen species (ROS), reactive nitrogen species (RNS), peroxynitrite (ONOO-) and H2o2 which, in excess, can all cause damage to normal cells throughout the body and the vasculature. Melatonin is also a potent antiinflammatory and it also up regulates the bodies own potent antioxidant system while activating the Nrf2 pathway which will increase the total antioxidant capacity (TAC) of the body. Melatonin can neutralize up to 10 oxygen radicals while vitamin E and vitamin C can only neutralize one radical each. Melatonin or its metabolites are also able to cross the blood brain barrier (BBB) as well as repair a perturbed or damaged BBB. Melatonin can also enter all tissues of the body, so it can get to most places that are damaged and can then exert its multitude of positive health effects in order to effect repairs as needed. All this while having a very good safety profile.
This study link above goes into greater detail of the many positive health effects of melatonin in the body beyond the heart and vasculature and discusses how melatonin can act to try and return the body toward homeostasis via its antioxidative, antiinflammatory, metal chelating, mitochondrial protective effects and radical scavenging effects to name just a few.
The following study link covers the potential of melatonin in heart failure, an area of medicine that could definitely use bolstering via the multiple actions of melatonin.
The following article discusses the value of melatonin in multiple cardiovascular issues that could fall into the category of CVD which is actually a broad range of anti-health issues that melatonin seems adept at working against.
This next link to a very brief abstract clearly states that melatonin can interact directly with the heart through melatonin receptors in the heart via receptors M1 and M2 to exert its protective effects directly in the heart while further offering protective effects against specific drugs known to cause heart damage.
There are many ways in which the heart can be damaged by other diseases or chemicals such as diabetes, and melatonin has shown the ability to help protect against some of this damage, especially mitochondrial damage throughout the body. These next two links discuss the damage that can be imparted on the heart in diabetes and how melatonin may help mitigate some of this damage.
The following abstract link discusses how melatonin can potentially lower elevated heart rate and shows that melatonin reduces the development of endothelial dysfunction and atherosclerosis, which are considered a crucial pathophysiological disorder of increased heart rate and pulsatile blood flow.
These next two articles discuss the role of melatonin and its multiple protective mechanisms of action as relates to myocardial ischemia / reperfusion injury that occurs after oxygen rich blood is restored after a blockage or partial blockage of a blood vessel to the heart.
In this next link, the potential of melatonin to express anti-hypertrophic effects in cardiac hypertrophy ( left ventricular enlargement) is discussed.
The following mouse study illustrates the utility of melatonin in myocardial infarction. While it is just a mouse study, it offers insights into specific mechanisms of action of melatonin in increasing cardiomyocyte production and heart regeneration.
The above studies help to define some of the ways that melatonin is likely to be heart protective as well as CVD preventative. There are many more studies to add confirmation to these multiple heart health effects of melatonin, so these are only a few of many studies, but the point being that melatonin continues to show its value in multiple areas of human and animal health and is definitely worth having a melatonin discussion with your doctor about possibly implementing into your health regimen moving forward. Since I am not a doctor, I can not recommend melatonin or dosing of melatonin for any health condition. I can say that I am still taking 106 mg of melatonin / night for over 4 1/2 months now after previously taking it at lower dosing for years. Dr. Neel continues to recommend 1 mg of melatonin for every kilogram of body weight for the treatment of his over 1,000 Covid-19 patients and he is experiencing great success at that dose in his patients.
My intent in the dose I am currently taking is to afford myself of the multiple health effects that melatonin seems to offer in many areas of human health, such as those listed in the next paragraph.
In this ongoing melatonin series, we have already shown that melatonin is useful for stroke prevention and recovery, Covid-19, COPD / Emphysema, Parkinson's disease, Memory and now we are showing the cardiovascular benefits of this remarkable molecule called melatonin. This melatonin series does not end here as will be shown in future additions to this series! The following links briefly mention some of the known health benefits associated with the use of melatonin such as cancer.
As always, it is imperative that you seek the advice of your doctor or healthcare professional before starting or testing melatonin to make sure it is safe for you at the dose you want to take and that it is not contraindicated with any of your current medications, supplements, vitamins and other alternatives. I am just showing studies that help to clarify all of the potential benefits that melatonin offers.
Art
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Hi there. I understand that you are not making any recommendations but would you share how you arrived at that dosage for yourself and what brand you use
The dosage was initially based on what Dr. Neel is using in his patients successfully for the treatment of Covid-19, 1 mg per kilogram of body weight, but is also based on the hundreds of melatonin studies I have read through the years. It isn't as high as the dosing used by Dr. Shallenberger or in some studies, but he is often trying to treat severe health conditions such as cancer, with melatonin, so I didn't feel the need to go that high since I am essentially using melatonin as a prophylactic and to try and achieve the health benefits that studies have reported, but I am open to testing higher doses if studies continue to suggest doing so, may be of better health utility.
Melatonin may exert its BP lowering effects through nitric oxide in the brain via increasing eNOS expression (at least it does in spontaneously hypertensive rats):
It is amazing to me how they continue to find melatonin receptors throughout the body and apparently the body knows well what to do with melatonin. In PD, they have shown below average receptor quantity in the SNparsC. Melatonin also seems to be working overtime in PwP to continuously protect and repair mitochondria, but the body is unable to generate enough melatonin on its own for this purpose. PD being an age related disease is important because melatonin levels decline sharply as we age.
Yes and they also have a couple that are both immediate release with time released in one capsule which is somewhat similar to what I do on my dosing, but use three different products which is not as convenient.
Yes, I think I have mentioned them before. I had multiple types because of different experiments and I continue to burn through my stock.
1. A 10 mg timed release product that I bought at Sam's Club under their house brand name of Member's Mark. It contains B-6, so I limit my intake of these ones to the amount of B6 I would like to get.
I’m sure you’ve said before somewhere but can you please remind me whether you take it all at night before bed or spread it throughout the day? I assume it might make you too sleepy?
Melatonin may indeed be helpful in the prevention and treatment of CVD. But I want to comment on the original premise that CVD is more prevalent in pwp. I was disappointed that these researchers meta analysis did not spend anytime discussing the effect of PD on the autonomic nervous system. How for example are pwp expected to address heart issues when they are caused by the same pathology that leads to PD. And if this is true then of course CVD is more common in pwp.
We can't always have every answer for everything that goes on in the body, but considering that both issues are essentially thriving and living off of elevated oxidative stress levels and elevated inflammatory levels as two main driving forces in their existence, melatonin seems appropriate for both as studies tend to confirm.
At this point, an HDM study in PwP seems warranted and needed to see just what the full potential of melatonin in PwP is beyond turning Covid-19 into a non life threatening disease.
Interesting article; thanks. I agree that there should be more attention to autonomic dysfunction and would like to see more studies using HRV as a biometric. I have wondered recently if dysregulation of nitric oxide synthesis plays a role in PD parthenogenesis (too much iNOS activity & subsequent generation of peroxynitrite, not enough eNOS activity, not enough paraoxonase activity) and could partly explain the association of CVD and PD. I also came across an interesting idea recently - that the vascular endothelium acts as an endocrine organ.
I would say very likely as regards iNOS as an inflammatory mediator that likely contributes to many of the aches and pains mentioned by PwP among other issues. Up regulated in the SN of PwP, this can not possibly be a good thing! Melatonin can reduce the vascular permeability associated with iNOS.
eNOS goes both ways in terms of inflammation.
Melatonin can act to inhibit iNOS and other inflammatory mediators.
It seems to be an issue of uncoupling of eNOS and I have some articles on my 'to read' list on what conditions and substances affect uncoupling. I may try to ask a question of Dr Nathan Bryan (of Neo40) about the people with ataxia who are taking arginine for protein aggregate inhibition. Dr Bryan says not to take arginine as that can make things worse in terms of inflammation - if one is prone to eNOS uncoupling it will push further into a vicious cycle of inflammation. It is interesting that the highest NO production in brain is in the cerebellum. I want to try to read more first so I can make sure my question covers everything.
Rhyothemis,It is all a bit beyond me but if you wish to pursue your wonderings the scienceofparkinsons guy Simon Stott is very approachable (he is after all a NZer like me)
Simon is very nice & considerate of my weird questions. He said he may get back to me on why high salt diet does not seem to worsen MSA mice or people with MS, and also if neuromelanin is found in turquoise killifish brains.
Incredible! I have been reading about melatonin for sometime and it has consistently received positive results, notably, against the corona virus. The dosage seems very high so I will increase, but not that much.
My most enthusiastic thank you for your hard work!
The story is not complete yet and melatonin shows much more potential health benefits in many other areas of health such as inflammatory lung diseases, cancer, fibrosis and osteoporosis/osteopenia. These are things that are rarely discussed when it comes to the lowly sleep aid melatonin. As time goes by and new studies explore deeper into the effects of melatonin on human health, new uses continue to be discovered for this molecule with a very good safety profile.
Look at this 10 mg RCT as a basic example of how even a low dose can offer benefit in terms of significantly increased glutathione, glycemic control, HDL cholesterol and total antioxidant capacity after just 12 weeks.
In the case of the study I linked to, it was a randomized, double blind, placebo controlled clinical trial which is considered to be a gold standard trial.
I have tried taking natures bounty dual spectrum and I have found that while it helps me get to sleep I seem to wake at 2am really wired and hyper. Is that normal? I don’t usually wake at this time once I fall asleep.
I remember when I first started taking melatonin many years ago, I had a similar issue. I would fall asleep and then wake up at 1:00 am and had a hard time getting back to sleep. I can't remember how that resolved, but I don't have that issue now, then again, I am still at 106 mg+ and sleep is definitely not the reason I am taking melatonin now. I am mainly interested in the other effects that melatonin has to offer, both known and unknown.
I have been taking 7 x 10 mg from just after the New Year(2021) and wake between 06:00 and 06:30 and my mind is raring to get moving. If I have a problem it is in not taking the 'starter dose' early enough to line up when I go lights out.
I have used Natures Bounty but found Webber sublingual tasted better than the 'chalkie taste'.
Thank you for the update Sapeye!I'm glad to hear that HDM is agreeable with you!
Do you think you are getting any benefit at your current 70 mg/night dose? Based on studies I have read, I suspect that benefit in PwP beyond the 10 mg and 50 mg dose studies may require between 1 ~ 2 mg per Kg /day/Bw. In the recent diabetes/melatonin study, they used 250 mg/day for 8 weeks to what appeared to be good effect. This dose appears to be slightly over 3mg per Kg/day/ Bw for me. Even higher than what I was thinking at 1 to 2 mg/Kg/day/Bw.
The dose used in this study, 250 mg/day over 8 weeks resulted in a significant decrease in mean systolic blood pressure (SBP), mean arterial pressure (MAP), pulse pressure (PP), weight, body mass index (BMI), waist and hip circumference (WC & HC), body adiposity index (BAI), abdominal volume index (AVI), conicity index and waist to height ratio (WtHR). These results were significantly better results in the intervention group than in the control group. A body shape index (ABSI) was significantly higher in the intervention group when compared with the control group in this RCT.
I remain at 106 mg+ of melatonin per night for 6 months now or less than half of what was used in this study above.
Art, you asked :Do you think you are getting any benefit at your current 70 mg/night dose?Yes, first it allows me to get to SLEEP and next , an unexpected benefit, the arthritis in both my hands has diminished. Not completely gone but now I get individual fingers having pain for short periods and then another finger might heat up or not.
My back pain has also lessened as has neck pain.
So Yes I am getting benefit at 70mg/night!
An unexpected benefit may be from melatonin, is the pain level I am having just 4 days after I had a dual hernia repair. Several friends who have also had repairs regaled me with stories of the pain after the operation to 'lift' my spirits. Ha. The Dr.'s Rx was Tylenol 3, this puppy has had enough times being bound up to know not to go near them... well I have so little discomfort, I have had one Tylenol (regular) pill each night in case and none in the daytime. I have to wonder if this might be from several months of 70mg of Melatonin daily.
Thank you very much for this feedback from your use of 70 mg melatonin/night! Very interesting and all the while you are significantly reducing oxidative stress and inflammation throughout your body while increasing your total antioxidant capacity and glutathione! Its a win, win, win!
There are a lot of aspects about melatonin I have not discussed on this forum, because frankly, I think people get tired of hearing about melatonin, but one of those non discussions is that melatonin has shown benefit in certain chronic pain issues in newer studies including RA, but the complete method of action('s) is not yet known for certain, but I think melatonin's antiinflammatory and OS decreasing effects may be a part of the reason. Here are a couple of studies which discuss chronic pain and melatonin :
Regarding your mention of reduced back and neck pain, recent studies have shown that melatonin offers protective effects to the mouse and rat spine and may potentially have repair effects to degenerated discs in rat & mice studies. Wouldn't it be nice to avoid many back issues just by taking melatonin? :
The more I read about melatonin, the more I am glad that I am taking HDM and I am now 6+ months in at 106 mg+ per day. There is still much more I could discuss regarding melatonin and health, but it can wait. I have experienced back and neck pain relief, but I don't know if it is from the melatonin or the borax, but I believe it is both because the borax gave me a ton of relief, but when I increased my melatonin dose, my back and neck issues just seemed to "smooth out completely" .
Sapeye, if you are interested, the borax lotion I have previously discussed on the forum will likely do away with your hand arthritis. I've seen it work very effectively and it has kept my severe psoriatic arthritis in "complete remission" for over 13 years.
It’s is very hard to get into our country as it is supposed to be prescription only but a few suppliers will ship it here so I am a bit limited as to what I can choose from.
Thanks Art for all the research. My husband is now on 20 mg every night. At one point he was taking 40 mg when he was having prostatitis. I subsequently reduced it back to 20 mg as another medication Harnal resolved the issue. Whereas previously night urination improved it is now about the same- some good nights and some not so good.
A friend told me that she and her husband were on 3 mg of melatonin and after 3 years they were experiencing forgetfulness and brain fog which went away after they stopped taking melatonin.
Do you recommend taking a break now and then lest it lose its effect over time?
I was working towards a dose of 60 mg but stopped at 50 mg and went back to 20 mg. I was unsure of a higher dose as a long term supplement. We started melatonin after your post on how melatonin helped nocturia in a Japanese study. When was that Art? It really helped.
Incidentally I also read in The A-fib Cure that increasing blood pressure meds can deplete your body of potassium and magnesium and cause atrial fibrillation. I think that could have been one of the causes too.
What your friends experienced is contrary to the literature, but some people are not able to tolerate melatonin for various reasons. Many people who find melatonin useful for sleep have been using melatonin for years and then there are studies using HDM for up to two or three years who do not experience the same as your friends. I have been taking melatonin for many years at 30 mg/night and at 106 mg / night since last year and have not experienced cognitive decline and in fact I feel as though I have experienced cognitive improvement.
Yes, magnesium and potassium deficiency can be contributing factors to A-fib and other problems. Melatonin is clearly heart protective.
The nocturia report was reported on a very low dose of melatonin such as 2 mg.
This new (May 2021) meta analysis (abstract) of random controlled trials (RCTs) adds further confirmation to the utility of melatonin in Cardiovascular Disease (CVD) and this is important for PwP because PD is a risk factor for CVD and melatonin has already shown benefit for PD itself. CVD is actually multiple types of disease or health issues related to the heart and cardiovascular system of which cardiac arrest would be one.
Here is their conclusion after reviewing the studies :
>>> ' The findings of this meta-analysis revealed that melatonin administration in humans as a cardioprotective agent attenuated heart dysfunction with a favorable effect on the LVEF. '<<<
The meta analysis is sometimes useful at weeding out studies that are biased or less than optimally designed so it is considered to carry more weight than an individual study.
I take 200 mg per day of CoQ10 (which is a generally recommended dose), when I remember with a fatty meal. I take 13mg per night of melatonin (5 mg didn't really cut it), but Art reckons you can safely go much higher.
I've seen that 1993 study in Syrian hamsters before and I am doubtful it would apply to humans and I question the accuracy of the study itself based on what Dr. Reiter has previously stated regarding melatonin dosing and animals. They have never been able to establish an LD50 for animals even at very high dosing of 800 mg/kg. In an 80 kg person, this would equate to over 10,000 mg / 10 grams. The study is 28 years old and perhaps the study design or methodology is flawed.
Here is a link that discusses the use of 1 mg up to 6,600 mg/day of melatonin for 45 days in humans and if what they are suggesting were correct in the hamster study, every human in this study at the 6,600 mg /day dose should be suffering cognitive decline and severe motor function deficit issues, but the only side effect they noted was drowsiness. They are talking about a 50% dopamine reduction in that hamster study at relatively low melatonin dosing for just 5 weeks and this should have manifested as cognitive decline and motor function deficits in the hamsters which they did not mention in the abstract that you linked to.
>>> ' Studies of human subjects given varying doses of melatonin (1-6.6 g/day) for 30-45 days, and followed with an elaborate battery of biochemical tests to detect potential toxicity, have concluded that, aside from drowsiness, all findings were normal at the end of the test period.[139,140] ' <<<
My impression and opinion of melatonin, based on what I have read in studies is that it seems like it tries to maintain homeostasis in humans and animals and that is why I say if there is such a thing as a smart molecule, melatonin might fill the bill. I think melatonin does an excellent job in PwP of slowing the degeneration process of PD for possibly up to two decades, but as melatonin declines fairly quickly with age and even more so in the SNpc of PwP. It can no longer maintain this level of protection when the melatonin levels decline with age and PD and with that decline comes a decline in glutathione and other antioxidants which I would think will tend to speed up the rate of disease progression. That would be my opinion.
Art: Thanks for this very helpful information. I have a heck of a time swallowing pills. Do you know if melatonin in gummy or chewable form is as effective as the standard tablet form? Right now I’m only taking 5mg which helps me as a sleep aid, but gives me a headache. I do have CVD, so would like to look into increasing my dosage.
Yes, oral melatonin is noted for headaches as a side effect, however, melatonin produced in the gut at at least 400 times the production rate of that produced by the pineal gland is not. I am currently trying to see if I can increase gut melatonin production and slowly withdraw oral melatonin. Melatonin produced in the gut does not seem to cause the side effects associated with oral melatonin intake. I am discussing this here :
Another new (RCT) human study (February 2022) further confirming that melatonin is useful in CVD (in heart failure) and this is useful for PwP due to their increased risk of CVDs.
Here is a relevant quote from the study abstract showing significant efficacy for the tested parameters in an RCT using melatonin :
>>> ' Overall, 92 patients were recruited, and 85 completed the study (melatonin: 42, placebo: 43). Serum NT-Pro BNP decreased significantly in the melatonin compared with the placebo group (estimated marginal means for difference [95% confidence interval]: 111.0 [6.2-215.7], p = .044). Moreover, the melatonin group had a significantly better clinical outcome (0.93 [0.18-1.69], p = .017), quality of life (5.8 [0.9-12.5], p = .037), and New York Heart Association class (odds ratio: 12.9 [1.6-102.4]; p = .015) at the end of the trial. Other studied outcomes were not significantly different between groups. '<<<
Thanks for sharing. Can you suggest a way to find a doctor who is knowledgeable about melatonin and it's dosage? I'm in Pittsburgh Pennsylvania. Thanks so much
This new study ( June 2022) adds further to the idea of melatonin for CVD by showing that melatonin alleviates aortic valve calcifications (CAVD). This fact is very important for PwP because of their increased risk for CVDs :
Here is an important and relevant quote from the study :
>>> ' Our study confirmed that melatonin could diminish OST medium-induced VIC calcification and block the NF-κB/CREB/Runx2 pathway. Additionally, this study demonstrated that activation of the melatonin/MT1 axis reduced the phosphorylation of NF-κB and CREB, which are the critical transcription factors of the Runx2 promoter. Accordingly, melatonin may down regulate Runx2 through the inhibition of the NF-κB/CREB complex activity in OST medium-treated VICs. The clinical trial study results validated the beneficial therapeutic effects of melatonin (10-mg tablets/day for 24 weeks) as a combined therapy for heart failure and the patients' comorbidities (18). These findings demonstrate the therapeutic potential of melatonin for CAVD. ' <<<
Are you aware of the link between beta blockers and melatonin? Beta blockers reduce the bodies natural melatonin production by up to 80% by specific inhibition of beta-1 adrenergic receptors. Many patients with heart problems are prescribed beta-blockers for long term use with no knowledge of the effect on melatonin synthesis (and Coenzyme Q10 production). My father has been taking atenolol for 30+ years and I’m certain it’s a contributing factor to him developing Parkinson’s. In the U.K. melatonin is not available OTC, requires a prescription and only for short term use.
I think what many people do not consider when it comes to beta blockers is that melatonin production in the body declines with age and it declines even more in PwP and then when you add the depletion effects of BBs on melatonin production, that seems like a very unhealthful situation that seems likely to increase the potential risk for PwP to get the diseases that PD increases the risk of getting such as CVD, leukemia, colon cancer, osteoporosis and osteopenia. Melatonin is noted for benefit against those diseases as well as PD and other age related diseases.
To update this article on CVD and melatonin, this new study (April 2022) shows that in myocardial infarction(MI) (heart attack), even if you haven't been taking melatonin regularly, if it is given within 3 hours after the MI, it can have positive health effects over the near term and long term compared to not getting melatonin :
' This pilot study demonstrated that compared to placebo, melatonin administration was associated with better outcomes in AMI patients undergoing primary percutaneous coronary intervention. '
' At 2 years of follow-up, 13 (13.8%) patients suffered the primary endpoint (3 deaths and 10 readmissions due to heart failure), 3 patients in the melatonin group and 10 in the placebo group. '
' The hypothesis-generating analysis found a relation between treatment effect and ischemia time and the authors concluded that melatonin administration within 3 h of ischemia onset reduces myocardial infarct size by approximately 40%. '
' The results of this pilot study indicate that treatment with intravenous melatonin in patients with AMI undergoing primary percutaneous coronary intervention is associated with a reduced incidence of death or readmission due to heart failure. '
This is the first study that I have seen using melatonin in people that have just had a heart attack and the results are good! The attached graph clearly shows that melatonin significantly improved longer term survival with just one dose given within 3 hours after MC. What this study doesn't show is what would have happened had the patients continued to take melatonin for the full study length of 800 days beyond the single dose given at the hospital.
Art
Increased Survival For Those Who Received One Dose Of Melatonin Within 3 Hrs. After MCI
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