(I will be doing this once my palmitoylethanolamide arrives)
"Chronic pain : two tested natural compounds may break pain cycle : could they be useful in neurodegenerative disease? 2022 cme30.eu/chronic-pain-two-t...
TWO TESTED NATURAL COMPOUNDS MAY BREAK PAIN CYCLE COULD THEY BE USEFUL IN NEURODEGENERATIVE DISEASE?
Chronic pain is a substantial medical concern because it is common, can be debilitating, and pain medications may be more dangerous than originally thought.
Analgesic drugs taken for even a few days are now claimed to increase myocardial infarction risk by 48%, using ibuprofen, and by 53% when using naproxen.1 Chronic use of NSAIDs like ibuprofen is claimed to increase kidney function impairment by 32%.2 Furthermore, the current opioid epidemic in the US is said to claim over 100 overdose deaths daily.
The challenge in pain control is both addressing the cause of the pain and switching off the pain signal. Is there a safe alternative? Two natural compounds are claimed to work together to reduce the underlying causes of pain. The first compound, palmitoylethanolamide (PEA), is an antiinflammatory fatty acid derivative produced by the body in response to inflammation-inducing damage;3 it acts at the site of tenderness, turning off the pain signal.4,5 The second, honokiol, a Magnolia tree extract, modulates pain perception in the brain. These two compounds are claimed not to cause dependence because they do not act via opioid receptors.
The nature of PEA was first identified by Nobel Laureate Rita Levi-Montalcini, the co-discoverer of the nerve growth factor and the pain signal development and transmission mechanisms.6-8 PEA is said to be an endocannabinoid, a natural neurochemical signalling molecule which does not bind to specific cannabinoid receptors, and which has no documented risk of dependency or adverse effects. This distinguishes it from most other chronic pain treatments.9
Several studies have established PEA as a powerful, peripherally-acting pain reliever.4,5 One study was conducted on 636 sciatic pain sufferers randomly assigned to placebo or one of two doses of PEA (300mg or 600mg daily). After 3 weeks, both pain reduction and quality–of-life scores were significantly better than placebo, and the larger dose had better outcomes.10,11
In pain studies, determination of how many patients would need to be treated to achieve a 50% pain reduction is called the “number needed to treat”. The standard number to treat for a useful pain intervention is less than 5, with 1 being statistically perfect (every treated patient achieves at least 50% pain reduction).
In this PEA study, the number needed to treat in the 600mg daily group was just under 3 at week 2 and only 1.5 at week 3.10,12 A number needed to treat as low as 1.5 is virtually unknown in pain reduction, indicating such a high level of effectiveness which surpasses most pharmaceutical standards.
In another PEA study with carpal tunnel syndrome, subjects were randomly assigned to three groups, placebo, 600mg and 1,200mg daily for 30 days.13 Nerve conduction measurements at the start and end of the study showed that PEA had slowed median nerve conduction. A faster nerve conduction indicates pain signals are being generated at the sore site. Therefore, this study indicated that PEA recipients’ nerve conduction improvements matched their reduced symptoms compared to controls.
In a study on patients with temporomandibular joint pain, subjects were randomly assigned to 600mg ibuprofen 3 times daily for 2 weeks or 300mg PEA twice daily for 2 weeks. The PEA group experienced significantly greater decrease in pain.14 Another study showed that mice treated with morphine plus PEA were less prone to develop morphine tolerance compared with animals on morphine alone.15 This suggests that PEA combined with an opioid could decrease the risk of tolerance and addiction.
Honokiol has been identified as the second compound that could approach pain reduction from a different aspect to provide deeper, complementary, more consistent relief. It operates in the central nervous system to affect how pain is perceived. It binds to GABA receptors, GABA being a neurotransmitter inducing calming, pain-dampening signals.16,17
Loss of GABA receptors and reduced GABA signalling is involved in the transition from acute to chronic pain, leaving the CNS exposed to continued stimulus from an old injury.18-20 Honokiol mimicks GABA actions, interfering with the chronic pain cycle by restoring a central natural pain-dampening effect. This is being followed up by pharmaceutical companies.21 Oral honokiol is quickly absorbed and distributed throughout the brain.22-24
An animal study has shown how capable honokiol is in its CNS pain-relieving action. Mice were injected with a variety of substances known to activate hyperalgesia receptors.25 Then they were treated with either honokiol or a control injection.
For each pain-inducing substance the mice were timed on how long they spent licking the painful site, longer licking meaning more severe pain perception. They were then timed on how long they took to withdraw their paw from a hot water bath. In each case, the honokiol-treated animals showed significant reductions in licking time, and significant increases in paw withdrawal time from the hot bath. These actions indicated a reduction in pain and demonstrated how honokiol can help break the chronic pain cycle.
By inference, a honokiol-PEA combination could provide a complementary dual action approach to chronic pain, without the risks seen with conventional analgesic drugs.
Chronic inflammation in the CNS may be involved in the pathogenesis of neurodegenerative conditions such as Parkinson’s and Alzheimer’s diseases. In a study of 30 advanced Parkinson’s patients being treated with levodopa, a cognitive test battery before and after receiving 1,200mg PEA daily for three months and 600mg daily for the rest of the year, found a significant and progressive reduction in both motor and nonmotor symptoms.26 PEA appears to have potential for some reversal of symptoms of chronic neurodegenerative diseases.
PEA is available in Europe under the trade name Normast® . A PEA-Honokiol combination product is marketed as ComfortMAXTM by Life Extension Europe, the European division of Life Extension, an American food supplement company."
DAMN! Look at this: Life Extension Comfort MAX – Honokiol & Pea for Nerve Support & Discomfort Relief – Gluten-Free, Non-GMO, Vegetarian - 30 AM Vegetarian Tablets - 30 PM Vegetarian Tablets amazon.com/Life-Extension-C... You get 30 AM and 30 PM capsules for $32! Both have 600 mg of Palmitoylethanolamide, and the PM has 180 mg of Honokiol. The seller says the Palmitoylethanolamide is micronized (not ultra-micronized I guess, but I read somewhere the whole UM superiority was not proven).
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I received my Swanson's version of honokiol recently and got the same result - took one capsule first thing in the morning and was sleepless the ensuing night. So it does not work for me. It might be helpful for people with fatigue.
That is a problem if it keeps you awake. It does not help me sleep. It may be helping with RBD. The reason I am taking it is, hopefully, for disease modification: "We discovered that subchronic honokiol treatment significantly ameliorated motor deficit, progressive loss of nigrostriatal DA neurons, and biochemical variations in a mouse model of PD induced by 6−OHDA. The [18F]FP-(+)-DTBZ PET evaluation further revealed recovery of VMAT2 expression that is reflected by reversal of DA neuron degeneration after honokiol treatment." sciencedirect.com/science/a...
I have been waking up feeling like I have a hangover lately. Not every day. Not sure why. Maybe Magnolia Bark, maybe it's my binaural beats, or maybe it is my brain healing. Most likely it is because I got weak and added Pepsi back to my diet.
Bolt, my husband has been taking Honopure by econugenics for about 4 weeks- better sleep, hardly any active dreams and less nocturia-fingers crossed. Thanks Bolt and Despe
Hadn’t heard of those before. There’s a newer nutraceutical that is based helping resolve the underlying triggers of disease called OptiCel (have bought it on OptiCel.com and Amazon) that addresses inflammation and oxidative stress. One of the scientists who created it is a member of the US National Academy. There are three varieties that all have a couple of the same ingredients to help with inflammation and others specific to that formula but I’ve been taking the Joint Health formula due to long term arthritis from serious injury year ago and my father who has PD has been taking the Heart Health which has helped his pain/stiffness, cholesterol and sleep.
Thank you Bolt for the valuable information. I am currently taking another brand of PEA. After reading your post I ordered Life Extension’s PEA. I think stacking it with lyprinol would be effective for inflammation .
I am new to the PD conversations, have been following and researching on behalf of my husband (71) who has recently been diagnosed with PD. I am very optimistic as I read the many studies, trials and treatments you post. My husband’s situation, however, is complex in that he also has been battling CLL for 10 years, has REM sleep disorder and peripheral neuropathy. Early on, we attacked the CLL successfully with Chinese Medical protocols under Dr supervision and he’s now been on Imbruvica for the past 4 years. His numbers are near “remission,” although the oncologist will not use that term. We attribute his success to combating with alternative supplements and lifestyle routines. Re: PD, he was just put on carbidopa/levodopa in Jan. So, with everything we study about PD, we flip to the cancer threads and studies to research possible counter reactions and systematic alignments. Interestingly, we are finding many correlations on the autoimmune, GABA, mitochondrial functionality, blood/brain, gut-related relationships, etc., between these two diseases. We are very careful, as we look now to proactively focus on the PD with a wholistic body strengthening and cleansing approach, especially as we begin to suspect the “why” of his diseases could be related. Soooo, niacin (mentioned in another thread) and PEA are of great interest to us. We’ve got the niacin covered. He would like to stop taking Tylenol for pain and the prospective longer term benefits of PEA seem promising…. we feel it is safe to try given his melting pot conditions. Long story short…can you suggest a true brand of PEA that can be affordably acquired in the US and that does not contain additives, particularly honokoil and luteolin, as these appear to have potential risks we’d like to avoid? Thanks!
Please explain the potential risks of honokoil and luteolin. I am seeking out PEA as well. And, welcome to this forum! It is great to have another proactive spouse amongst us!
Please look in to Citicoline and the importance of all the other B vitamins as well. I think you will be pleased to learn what a difference they can make!
For those, like me, that did not know what CLL was: "Chronic lymphocytic leukemia (CLL) is a type of cancer of the blood and bone marrow — the spongy tissue inside bones where blood cells are made. The term "chronic" in chronic lymphocytic leukemia comes from the fact that this leukemia typically progresses more slowly than other types of leukemia."
So... I have not used palmitoylethanolamide yet. I have two types on order.
- For quality, the Normast might be the best choice. I think they were used in some trials (not sure): naturitas.us/p/supplements/... $31 for 20 tablets. (I did not order these ones. I am too cheap for them).
- For price, I ordered this powder: $50 for 100 grams. USA LAB Tested Bulk Ultra-micronized Palmitoylethanolamide Powder 99% Pure (100 Grams) amazon.com/gp/product/B07NJ...
Thank you. The powder version is interesting. I like the idea that we could adjust dosing easier, if need be. We’ll check it out and look forward to hearing how it works for you.
Thank you, ccraspberry, for the welcome and pointing to Citicoline. The only thing I’ve heard about it is that it can cause sleep issues. I’ll read more about it.
And, sorry for not defining CLL, Bolt... my bad.
I realize it’s evident that everyone’s system is different… what works for one may not for another… my husband seems to be a puzzling mixed bag of goodies.
In addition to his RX (IB for leukemia and the CL for PD) he is currently taking glutathione, on a powerful supplement called Complete Foundation, takes additional D3, B12, B3, Lutein, papaya drops, a glutamate scavenger, is vegetarian, and exercises daily…stationary bike, works the garden, plays in a band (guitar abates the tremors…yea!). All in all he’s frustrated with the onslaught of PD symptoms yet managing quite well as we look to answers and ways to arrest the progression.
Although the information on Honokoil is limited concerning side effects on humans, there are indicators of increased bleeding, which is a significant caution to anyone with a lymphocytic, blood cancer conditions or on Imbruvica… as is my hubby. It also has references to kidney complications. My husband’s father had only one kidney and history, and his grandfather was a kidney transplant. This is another big reason we want to take Tylenol out of the mix; however, it is the only over-the-counter pain med his traditional doctors have approved….sigh.
Luteolin has a strong caution against being used by cancer patients. Even though my husband’s type of cancer is not specifically referenced on its compromising list, he’s had several skin carcinoma cells removed in addition to having CLL….so that’s enough of caution for us at this stage in our investigations.
Background: In addition to his oncologist, neurologist, and our excellent GP and chiropractor, we met with a chronic disease specialist/MD earlier this month who reviewed my husband’s labs thus far, ran a mycotoxin lab, and plans to order additional labs exploring toxicity levels with the expectation that customized IV/chelation, O2/autophagy, and LDA immunotherapy treatments may be in my husband’s future… is pricey and not covered by insurance, so TBD.
This past week, we met with our long-standing specialist (DO), whose practice specializes in the east-meets-west approach, to go over his genetic markers and what we are learning now. She ordered some new labs focused on nutrition and GI tract health, and referred my husband to an MD whose specialty is pharmaceutical with emphasis on RX and supplements… how various meds/treatments interact with one another, especially in complex patient diagnosis situations. We are doing our homework now so that he can best advise.
It’s a long and winding road …we have a super supportive fam and a good med team coming together… which now includes this fantastic forum!!
Welcome to the forum although I wish I never had to welcome you or anyone with health problems.
My husband was diagnosed with PD 4 years ago. His path is mostly a naturopathic/homeopathich one. Having said that, I believe Ozone therapy is a must, especially for cancer patients. Diet is also very important, starve carcinogenic cells by avoiding any type of sugar.
My mother's sister passed away with CLL but several years after diagnosis.
Thank you Despe. I am VERY sorry to hear your aunt passed from CLL. Like PD it’s a disease that can morph and become extremely difficult to regulate. My husband was fortunate to have been medically guided into an intense Eastern medicine therapy when he was first diagnosed and extremely sick. It took time, and eventually cleansed his organs and strengthened his system, to the amazement of his oncologist. We believe it is one factor behind why now the Imbruvica/Ibrutinib has been so effective.
Among other treatments, he is considering O3 therapy, as it has positive notations for both of his diagnosis, especially the PD. We are looking at ways to increase oxygenation to improve functions in his substantia nigra, reduce potential A-Syn protein blockage as well as trying other metabolic assists that feed the brain mechanics, improve waste disposal and ganglia synopsis.
Yes, we agree, diet is critically important! The gut brain axis/Vagus nerve role in reducing inflammation and maintaining energy homeostasis is of huge focus for us. We are lacto-ovo vegetarian and have always predominantly gone with a Mediterranean diet. Love cultural veggie dishes of all kinds. We are fortunate to have an organic permaculture farm so with the exception of meat, we eat the rainbow. We avoid processed sugary things …is harder to do when out and about, but we try. He does not drink alcohol. He has a sweet tooth that we mainly keep satisfied with low glycemic dark chocolate or real fruit and use substitutes like stevia or raw honey when a recipe calls for sweetening.
We feel we are doing a lot “right”…yet, there’s always more to learn and consider. Like many others we talk with, we haven’t been able to pinpoint cause… head trauma, genetic markers, exposed to work environmental toxins when young and “bullet proof,” molds, a tick bite ??? so it’s challenging to find definitive solutions….and super frustrating when symptoms flare up.
What gives us hope ….new treatments and body system discoveries that cleanse and realign whatever caused the egregious imbalance in the first place, rather than just treat symptoms (however we are exploring those relieving assists too)….and having a place like this where people are sharing studies and experiences.
Thank you for the article you shared, I’ll read it in the morning.
Caveat…After recently researching the honokoil, we have this formula on the list to review with the pharmaceutical doc we’ve been referred to because it contains magnolia bark. My husband only takes this as an assist, as needed, so at this time we aren’t overly concerned with his exposure so far.
Frankly, the calming effect of this overall formulation works!
It also contains the Citicoline, which ccraspberry recommended. Interesting. My husband has not had the noted sleep disruption when he takes it….but it’s on our review list too.
It also includes Danshen Root (Traditional Chinese Med for brain/neuron health…getting rid of harmful glutamates…major cool! ) ….as well as L-Theanine and Calcium Pyruvate ….all great stuff in the PD solutions box.
Thank you, never read about Danshen before, used primarily for heart issues in Chinese herb mixtures, reported to lower BP and lipids. Makes sense as inflammation problems do impact heart system. Can not take on blood thinners and monitor BP if already taking BP meds.
Calcium pyruvate was new to me too, said to help metabolize fat breakdown with anti-inflamatory properties for gut.
This is what I found on Magnolia Bark - honokoil:
topically: Contact dermatitis.
- Dermatologic
Topically, magnolia bark has been associated with reports of allergic contact dermatitis. Magnolia bark extract is used in anti-aging facial creams (92463,92468,95030). In one case, topical corticosteroids and discontinuation of the product resolved the dermatitis (95030).
- Endocrine
In a clinical trial of an oral combination product containing extracts of magnolia and phellodendron, one patient reported thyroid dysfunction (14349). However, it's not known if this side effect is related to magnolia or some other factor.
- Gastrointestinal
In a clinical trial of an oral combination product containing extracts of magnolia and phellodendron, one patient reported heartburn (14349). However, it's not known if this side effect is related to magnolia or some other factor.
- Neurologic/CNS
In a clinical trial of an oral combination product containing extracts of magnolia and phellodendron, one patient reported shaking hands and perilabial numbness. Another patient reported fatigue and headache (14349). However, it's not known if these side effects are related to magnolia or some other factor.
- Psychiatric
In a clinical trial of an oral combination product containing extracts of magnolia and phellodendron, one patient reported sexual dysfunction (14349). However, it's not known if this side effect is related to magnolia or some other factor.
From theraputic Natural database info
This is the hard part for me as so many supplements seem promising and I don't want to hurt HWP in anyway. Sometimes my trial of a new supplement will not go so well.
Thank you for all that good info on magnolia bark!
My husband began using the Glutamate Scavenger II when he was first diagnosed with CLL and going through an intense Dr supervised program that incorporated Chinese Medicine. In addition to his western med team of oncologists and specialists, he saw a certified TMD physician several times a week who monitored, tested and administered customized formulas for a 6 week period. The monitoring and formula adjustments tapered off over a 5year period as he showed improvement. Although blood thinning is always a concern with CLL, it was not the main concern at the time and because he uses the GS2 as an assist/as needed, no negative impact has occurred as far as we know. To add honokoil now to a PEA formula that is showing promise with PD however may not be advised….we don’t know.
PD had not manifested back then. Sooooo, now with its onset, adding Carbidopa/Levidopa with the biologic Imbruvica for the CLL we are reevaluating all his supplements. Making sound choices as we weigh benefits and cautions given my husband’s complexities is tedious. We are meeting with a MD soon who also has pharmaceutical credentials to do a deep to review with us. For example, my husband is not permitted to eat grapefruit or Seville oranges with the Imbruvica because they inhibit CYP3a4 and slow the active ingredient. Because of this, up to now we were advised to be careful to avoid supplements with citrus based vitamin C and now have questions about the alternatives to ensure efficacy helps both conditions. Sounds simple. Not.
I totally empathize with “This is the hard part for me as so many supplements seem promising and I don't want to hurt HWP in anyway. Sometimes my trial of a new supplement will not go so well.”
Yes that's husband, I am his healthcare advocate. I can not imagine how hard this journey would be if you without a supportive friend/spouse/relative etc.
"The question of whether ultra-micronized palmitoylethanolamide (Normast®, a food for special medical purposes) can promote neuroinflammatory resolution and possibly a slowing of the progression of PD has been evaluated [185]. The effects of palmitoylethanolamide were investigated in a prospective observational study comprising 30 individuals (16 males and 14 females, mean age 73 ± 8 years, mean duration of PD 10 ± 5 years) receiving drug treatment for PD (levodopa 200–1150 mg) and, in some patients, other PD medications, such as dopamine agonists, monoamine oxidase inhibitors, or catechol-O-methyltransferase inhibitors. The study lasted 15 months, with ultra-micronized palmitoylethanolamide administered at a daily dose of 1200 mg for three months, as add-on to levodopa and other PD medications, and subsequently at a reduced dose of 600 mg daily for up to 12 months [185]. Pharmacotherapy with levodopa or other drugs was maintained constant during the treatment period. Clinical assessment of motor and non-motor symptoms, using the revised Movement Disorder Society/Unified Parkinson's Disease Rating Scale, was performed before the addition of palmitoylethanolamide and at months 1, 3, 6, and 12 after addition [185]. Add-on administration of ultra-micronized palmitoylethanolamide resulted in a significant and progressive reduction in the total MDS-UPDRS score [185]. The mean score difference between baseline and end of treatment was significantly reduced in most motor and non-motor symptoms. Furthermore, the number of participants presenting with symptoms at baseline was reduced following 12 months of treatment with ultra-micronized palmitoylethanolamide. Side effects attributable to palmitoylethanolamide were not reported by the patients included [185]. In summary, the results of the observational study suggest that ultra-micronized palmitoylethanolamide as an adjuvant treatment slows disease progression and reduces disability in individuals with PD and may, therefore, be a disease-modifying compound [186]. However, a randomized controlled trial including a control group and comprising a larger sample should be conducted in order to confirm the findings."
The Normast is expensive. I am going with what I put in the original post: Life Extension Comfort MAX – Honokiol & Pea for Nerve Support & Discomfort Relief – Gluten-Free, Non-GMO, Vegetarian - 30 AM Vegetarian Tablets - 30 PM Vegetarian Tablets amazon.com/Life-Extension-C... You get 30 AM and 30 PM capsules for $32! Both have 600 mg of Palmitoylethanolamide, and the PM has 180 mg of Honokiol. The seller says the Palmitoylethanolamide is micronized (not ultra-micronized I guess, but I read somewhere the whole UM superiority was not proven).
Although I also ordered 100 grams of ultra-micronized PEA from Amazon (I linked to it earlier). I may work out where I use a combination of the two.
I have seen a neurologist. He diagnosed my REM Sleep Behavior Disorder. April 2nd, 2021. He told me I was doomed (in about 10 years. I guess that would be 9 years now).
I don't mind the question at all.
My greatest hope is that by helping sort this out for myself I can help others.
I should not have posed for a holy picture there. I am the least in this group of truly heroic and strong people. I am honored to just be in your all's company.
Great article! Being lacto-ovo veggies, we are constantly addressing balance with regard to what we do and do not eat or add supplementally. FYI…since the PD diagnosis, mannitol is something we’ve been looking into. That’s a new one for us.
I have not dug into Luteolin, but have heard good things about it, so I am in no position to suggest cutting Luteolin. If you Google luteolin parkinson's you find some positive information. I could not find a study though.
I landed on PEA + Honokiol because somebody suggested Honokiol for my REM Sleep Behavior Disorder, so I was already taking Honokiol when I started PEA (yesteday).
How is your HwP doing on PEA + Luteolin? Which brand please?
Thanks, BU. The brand my 68 year old husband uses is Gold Health. It's micronized, not um. He doesn't have REM SBD, just tremor dominant PD, treated till now with Azilect alone which isn't doing much. He started the PEA a few months ago and it appeared to cure a nasty shooting pain he had in his toes, though the pain has just recently recurred to a lesser extent. I don't think he is deteriorating though he thinks that he is stiffer and that his handwriting is worse. He added the Coronet a couple of months ago - here's hoping. I know you use Melatonin 10mg - that hasn't helped with the REM SBD?
I don't use the Melatonin anymore. I suffer from major depression and it seemed to make it worse (probably not, but it seemed that way to me).
Now I am using Honokiol/Magnolol (from magnolia bark).
I was using Swanson that says it is 90% Honokial, 30 200 mg capsules for $5.09 swansonvitamins.com/swanson... (it is really probably honokiol/magnolol combo).
But now I started taking Life Extension Comfort MAX – Honokiol & Pea for Nerve Support & Discomfort Relief – Gluten-Free, Non-GMO, Vegetarian - 30 AM Vegetarian Tablets - 30 PM Vegetarian Tablets amazon.com/Life-Extension-C... You get 30 AM and 30 PM capsules for $32! Both have 600 mg of Palmitoylethanolamide, and the PM has 180 mg of Honokiol.
Thanks, BU, for reminding me about SR Niacin 250mg. Which brand do you currently use and where do you get it? Also do you get any flushing from it? - my HwP would not tolerate flushing. I'll be very interested to know how you find the PEA/Honokiol combination. You keep telling us that you're only high school educated - it must have been one amazing high school!
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PQQ combined with Ubiquinol - info and experience? 
