Whether coffee is good or bad for you is a topic with many opinions to be had. Too much caffeine and all its baggage or benefits – you could spend days debating that. Most of the scientific inquiry into coffee’s effect has focused on caffeine’s pharmacology. However, it turns out a completely different compound found in coffee may actually be helpful in suppressing, and possibly reversing, neurodegeneration. That is a general term for the underlying process involved in Parkinson’s disease as well as Alzheimer’s disease and Lou Gherig’s disease (Amyotrophic Lateral Sclerosis). I don’t usually get too deep into the scientific details but in this case? I am. Too bad. Scroll down to the section where I make my own snarky comments if you want… Oh, wait. That means pretty much the whole post. The article I posted a link to below is from the Journal of Neurotherapeutics entitled:
Neuroprotective and anti-inflammatory properties of a coffee component in the MPTP model of Parkinson’s disease.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3557367/ 
Briefly, since doing such experiments in humans would not be ethical, scientists developed an animal model for Parkinson’s disease using the neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Yeah, we know what it does after lots of humans found out about how MPTP the hard way from illicit narcotic use. Anyway, over the decades of research into the molecular components all working together in nerve cells scientists have discovered intriguing details about how certain proteins function. The tau and α-synuclein proteins, for example, have their regular duties but when they accumulate too many phosphate groups on them (from protein kinase activity) they begin to have harmful effects that wind up causing neurodegeneration.
The compound referred to in that article is called eicosanoyl-5-hydroxytryptamide (EHT) and it has been shown to have a few different activities that are beneficial. It has both anti-inflammatory and anti-oxidant activities (yeah, those always seem so vaguely mentioned for just about every nutritional supplement) and a well characterized mechanism for enhancing the activity of phosphoprotein phosphatase A2 (PPA2). This is a big deal since PPA2 is the major means of removing phosphate (PO4) groups from serine/threonine amino acids in large proteins (pretty much all the different cellular worker bees). In many cases, this removing of PO4 groups is important for the continued normal activity of these proteins. [From the article cited above] EHT functions, at least in part, by promoting the methylation of phosphoprotein phosphatase 2A (PP2A) by directly inhibiting the interaction between methylated PP2A and its specific methylesterase PME-1 [The article describing this is cited in that article above, ref #6]. EHT is helping keep the PME-1 enzyme from ‘turning off’ the PPA2 enzyme by blocking its access somehow. It’s one step in this cellular regulatory process but this mechanism of action has some good experimental data backing it up.
Since PPA2 is involved in regulating so many different cellular processes, having EHT keeping the PPA2 enzyme working properly is the rationale for EHT being an effective agent for treating many neurodegenerative diseases. It probably isn’t necessary to say this but based on those findings it is better to suggest that the EHT molecule slows down a degradative process. This is opposed to the notion that EHT actively stimulates better neuronal function. To me at least that fits better with the narrative about the EHT as an anti-aging product that works against cognitive decline.
That tau protein I referred to above? That is a key part of the neuron’s internal microtubule network, or scaffolding if you will. Tau proteins need to function properly to enable our brain cells to have neuronal plasticity. Ahh yes, neuronal plasticity, that magical process our brains make use of to adapt to just about everything that happens to us. It is a huge part in the hope all of us survivors have for our recovery. EHT appears to keep tau proteins from getting torn down by a process called hyperphosphorylation (because PPA2 activity prevents it), thus preserving their usefulness. That book on neuronal plasticity I linked to is quite in depth so go for it if you’re into that stuff.
My Comments
EHT has been studied for close to 20 years and has just been released as a nutritional supplement as of May, 2015. There is definite optimism about the potential for EHT to ameliorate the neuronal damage that brain injury survivors of all types try to overcome. I suppose you may hear of it mostly from TBI treatment advocates since they use well-known but unfortunate professional athletes. Just about any sport where head injuries are common is going to have some athlete touting the benefits of EHT soon. I would say that the chronic traumatic encephalopathy (CTE) community will be very interested in EHT. CTE is essentially brain damage as the result of a long series of head injuries on the level of concussions or milder – the damage is easier and easier to cause with each successive impact. Let’s see, how many practices and games over the high school, college and pro years? And that goes for any sport with the high risk of crashes. Or just being a modern human who rides in a car. You get my point though. You’re just a regular human – but to market something they use a famous person.
EHT is a marketed by Nerium International in partnership with Signum Biosciences. You may have heard of them from the line of Nerium anti-aging skin treatment cream. I’ll leave you to your own opinions about that kind of sales model or about the safety & effectiveness of the Nerium AD skin care/anti-aging cream. This is not what this post is about. I’m talking about an additional direction Nerium is now delving into, the cognitive effects of our aging brains. It is called a ‘mind enhancement formula’.
- Would I take it? I’ll cut to the chase. I can’t say that I will try it right now. Just the cost alone is a barrier but I’ll wait and hope that people do get some real benefit from this product. I’m not happy that it costs so much though. People recovering from brain injuries are not likely to have plenty of money floating around. And don’t give me that bullshit about your brain being worth it and all. It has to compete with things like food, rent and those dang utility bills. I will say though that if it does help brain injury survivors this could be a great thing. We’ll see.
———– - The product they call EHT is actually a mixture of vitamin D, B vitamins (B12, folate and B6) involved in methyl transfer reactions, alpha lipoic acid (I wonder if it is the purified R-isomer) and a Huperzia serrata extract called Huperzine A (which is a novel acetylcholinesterase inhibitor marketed in the early 2000’s as a supplement/drug treatment for Alzheimer’s disease and dementia). There are also other items such as selenium and magnesium citrate. Thus, all those scientific studies Nerium cites were not conducted on their whole product, only the EHT molecule itself. The combination of just the D and B vitamins, plus the alpha lipoic acid might compare very well in a double-blinded clinical study against the whole EHT product. Can’t seem to find any of that stuff online though…
——— - I actually take alpha lipoic acid as well as krill oil and astaxanthin, myself. Those supplements are used for their anti-oxidant properties, particularly the hyperglycemia-induced oxidative stress in diabetes. You know, that damaging process that leads to nerve & tissue damage and ultimately amputations if it isn’t dealt with successfully. I started taking them long before my crash when I was still a naughty little triathlete and had borderline Type II diabetes.. Actually more like a bigger, pear-shaped triathlete but those overweight days are over for the time being and my blood sugar patterns are normal. Am I recommending those instead of the EHT product? No, but I am letting you know that I use them and think they help me – for the glucose tolerance problems, exercise recovery and now the TBI recovery process. That statement is just my own anecdote – not a guarantee they will do the same thing in everyone.
———-
- No dosage information so far. What is missing from the list of ingredients that I can find on their website is the actual amount of these things in each dose you’re directed to take. I do know that Huperzine A has a suggested upper limit of 200 mcg (that’s Micrograms, not Milligrams) per day before adverse effects can develop. It is also NOT a substance anyone with a seizure disorder should take. It can also adversely affect certain heart conditions, peptic ulcers, lung conditions such as emphysema, and urinary tract or gastrointestinal tract blockage. No easily found dosage information and not any mention of these complicating conditions gives me plenty of concern. The person I spoke with who is now selling this product is very confident that there are no adverse effects. To be blunt, I call bullshit on that. If the Huperzine A content is so low as to not have any risk of side effects, based on its known mechanism of action (blocking the enzyme that breaks down the neurotransmitter, acetylcholine) I know that it also is so low that it won’t have any therapeutic effect. I would submit it’s only there for marketing effects if they’re not giving much information on it.
———- - The EHT compound has been studied like a prospective drug molecule is usually studied. The potential market for this worldwide or even in the US with our aging demographics has got to be very big. So why hasn’t any major pharmaceutical firm done something with this drug? Sure, it is patented; that lab in Princeton that worked on it and Signum Biosciences appear to have control over this molecule. But let’s be real here. Money is something big pharma has a lot of and it isn’t a stretch to think one of those large companies would get in on this product if it was that effective in actual wild type humans (meaning in every day non-controlled life).
——— - That is, if there was actually any real therapeutic benefit to taking EHT. I don’t know if the product will prove effective but just listen to some of their promotional videos for yourself. I know I take the endorsements of professional athletes, those leading medical experts that they are, on medicines seriously, don’t you? They are CERTAIN it is just the thing you should be taking right now. Everybody should. You know, if you want to keep your mind healthy. Of course you do, don’t you? I want to see some clinical studies with this product before I think about taking it. I also don’t want to read some studies that Nerium touts on their website but that’s just me. To be fair here, there actually are some professional athletes that are or who have become medical doctors so take my snarky comment as just that, an unjustly broad generalization for the purpose of this post.
——– - EHT 2020 mentioned in the studies I found online is NOT the EHT I’m talking about in this blog post. EHT 2020 is etazolate hydrochloride, a phosphodiesterase inhibitor also being studied in Alzheimer’s disease. Don’t confuse the two; they do different things in nerve cells. The Nerium site calls EHT:
- our exclusive and patented EHT® extract – a natural mix of bioactive molecules isolated from coffee.
Yeah, try getting that stuff past the FDA regulations…
———- - I take issue with some of the dumbed down science explanations used in those videos. I also heard some inaccurate language about EHT’s effects. The therapeutic effects of EHT are not permanent, even though you might hear that message. If you understand medicines at all you would know that very few pharmacological effects are permanent, except for maybe toxic effects like liver & kidney failure causing the need for a transplant or death. And yes, that last sentence was sarcastic and not truly necessary. It is however, TRUE and accurate. I do not consider even the videos with the Princeton scientists to be telling a fully informative and understandable story. When they say permanent effects or reverses the damage they probably mean those effects are persistent or durable as opposed to transient. But remember, the people selling these products are in business for themselves – and you definitely have to keep taking the product. I know the person I spoke with is not a doctor but that doesn’t mean the person you might deal with isn’t a health professional should you want to try EHT.
——— - EHT is expensive. From what I found on the website a 3-month supply is $210 for a one-time purchase. Your doctor can’t prescribe it and expect your insurance company to cover it. Heck, your doctor may not have even heard of it. Again, that doesn’t mean EHT is junk. I just don’t consider it proven yet as an effective product. In the lab? Sure but those are controlled circumstances and we also do not know what results that didn’t look good were thrown out. That is definitely my own cynical statement but I know it happens. Although at least in the basic science labs this practice of making the data look good is not rampant. I have no illusions about the supportive materials the company promoting and selling it show you. ——–
- It isn’t considered a drug product like other medicines we know of. That doesn’t mean it isn’t effective but it does mean the FDA has little to say about it as far as any medical conditions EHT is indicated for. The claims nutritional supplements have to make are so much less stringent than those for new drugs, at least at this time. That means they also do not have to provide any proof at all that the product actually works as hyped, I mean advertised. Of course they’re going to provide testimonials and anecdotes and such from successful users. But as a friend of mine cheekily once said, the plural of anecdote is not data. The scientific article I posted at the top to refers to the effectiveness of just the EHT molecule (not the mixture in that product) in helping reduce the neuronal damage in Parkinson’s and Alzheimer’s diseases. Where are the scientific results validating its benefits in brain injury recovery (of any kind)? If I’m right, the folks at Nerium are implying that its effects in animal models (not humans yet) of Alzheimer’s and Parkinson’s will also apply to fixing such traumatic brain damage as axonal shearing and other neuropathologies. Again, I call marketing bullshit. Feel free to point me to actual data and I’ll read it.
Nine of All Trades 
Interesting, Peter. This is a perspective that not all TBI sufferers can share!
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Thanks, I think. What are you referring to? Learning that lesson about the LED screens messing up your sleep and realizing other people need to know it when a BI locks them onto their device even more?
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I mean that your educational background really adds to your perspective!
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Hi Peter, I met you on the bike with Allison Kalsched a few years ago. I have been taking EHT and I distribute it. It’s unbelievable. Would love to share my experience with you. Give me a call 973-219-1170.
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Hi Judy,
Please tell me if EHT Nerium helps heal concussions. I do not know enough about this product at this point.
Thank you,
Lu
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Okay, cool. Let’s get together. I’ll try to remember to give you a call.
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Great, Peter. Looking forward to hearing from you. I’ll remind you if you forget 😉
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Here is another post re:EHT posted by a survivor of TBI. He refers to ME Sports — originally the two Princeton scientists of Signum Labs started that company. They have now decided to work exclusively with Nerium .
http://www.tbirider.com/?m=201410
The cost for preferred customers is 50 a month (+tax and shipping). It is more expensive if you just buy it as a retail customer. That must be what you looked at, Peter.
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This is a blog from an TBI survivor. He refers to ME Sports — originally the two Princeton scientist started that company. They have now decided to work exclusively with Nerium International to bring EHT to market.
http://www.tbirider.com/?m=201410
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Oh, Daniel and I have been doing quite a lot of chatting about this stuff. About ME Sports and Nerium International, too. Don’t you worry. We’d both like to see actual data instead of anecdotes and testimonials.
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I have a friend who distributes Nerium EHT and wants me to try it (I’ve had several concussions and my dad has dementia, though it’s of a different variety – frontotemporal dementia). I found your post really helpful. Having been disabled for a couple years due to a prescribed drug (Depot Lupron), I’m wary of trying new mess and supplements. I think I’m going to politely decline until I can see better research. I really appreciate your post.
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http://supplement-geek.com/nerium-eht-review/#comment-107845
Here’s another person’s review of EHT. He’s not quite so down on it as I am. This is rather blunt of me to say but if this person really is a friend they’d give you a month’s worth of the EHT product to see if you respond to it. If it helps you, then pay for it but not before.
As an update, I have taken it myself. I tried it for a month and I felt no difference at all. No adverse effects either I should clearly note. Since then, I gave the other 2 boxes (you had to buy 3 months at a time) to a couple of other TBI survivors who also saw no benefits. Another important point to add is that none of us felt anything at all when we stopped taking it, too. Everyone I heard touting its benefits claimed they noticed how things got better for them within a couple weeks.
The difference between a traumatic brain injury versus an acquired or ‘organic’ BI is significant in that abrupt physical injury such as axonal shearing usually only happens in trauma situations. EHT supporting proper PP2A activity is just not going to help that but who is to say whether your situation that happened with leuprolide will respond? Maybe it would. At least I can add my voice to those saying they experienced no side effects.
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Hi Peter!
I want to first acknowledge that I do distribute EHT with Nerium for credibility’s sake, but I am also a therapist on an inpatient psych unit at a VA. I am also a self-proclaimed nerd who reads medical journals in my spare time. I would like to add a few points just as additional info for you and your readers to do whatever you want with.
– EHT is a supplement that works at its most effective rate after 90 days. People who say they noticed a difference in a few weeks either had minimal need for the supplement or it was a placebo effect.
– A large trend in physical health and mental health research is showing inflamation of various organs to be either a root cause or significant factor in various diagnoses – anxiety, depression, peripheral neuropathy, and migraines to name a select few. When used correctly, EHT has been shown in the 20 years of research you mentioned to reduce inflammation in the entire body!
And last but not least, even if you don’t believe in the 20 yrs of science behind Princeton’s labs, EHT as a supplement also contains Vitamins D, B6, B12, Folate, and Magnesium. Most Americans are deficient in these nutrients if they eat a standard American diet.
Like I said, the info is just for sharing- I’m not trying to convince anyone of anything. EHT and its benefits are something that even I am still understanding, but the more I read for my job in acute psych, the more it dovetails with EHT’s ingrediants and benefits!
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I was a Pharmacuetical drug rep for years and I do agree with Peter. Peter, you have pointed out some very important scientific data that needs to be heard.
The one thing that we as humans must remember Nuetracueticals are not FDA approved so companies can put just about any concoction they want together and call it a miracle drug.
Now, I do want to point out one thing. There are some very good Nuetracueticals in the marketplace that can and do work; joint supplements for example but even an orthopedic doc will tell you it does no good to take these if you are bone on bone and of course have no cartilage left. So, no point in taking these supplements if you are too far gone. One must start taking supplements before things get to be a 10 on a 1-10 scale.
Since there are so many contraindications with EHT I would hesitate to take this supplement. At least some responsible companies post the MCG in there Neutraceuticals.
Thanks for such a well written article explaining the pros and cons of EHT…
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I have been on EHT for over a month. I noticed results in a week! My ADD didn’t seem to be a problem anymore! I will continue on the product. I showed my doctor my EHT box and said all the ingredients are a good “cocktail” for the mind.
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Hi Krista,
I’m glad it appears to be working for you. Encouraging news.
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Well, Kelsey, since I’m not able to directly reply under your comment I’ll have to do so here. Just where are the articles demonstrating the reduction in inflammation due to EHT? Please provide me with links. Are these the results of clinical trials or merely anecdotes and testimonials? Are these findings based on the EHT molecule alone or the EHT combination product – that already has B vitamins, alpha-lipoic acid and vitamin D besides EHT?
And furthermore, if it is so helpful how come I see NOT ONE medical journal article discussing its benefits for brain injuries? Why no recruitment for clinical trials in any of the brain injury centers around the country?
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I don’t want to create any conflict here, and I do want to say I use and distribute EHT. I have several physicians who take this product, and they required more specific information than what’s found in the company’s standard videos. There is a publication called EHT Whitepapers, and it contains studies and articles done on EHT in regards to Tau, inflammation, Parkinson’s disease and more. These articles are from a publication called Pubmed, and while some are summaries, some are the full trial. They are found on the right side of the publication, on the left are articles and information from Nerium and Signum Biosciences. I also have had a pharmacist look at these articles. My understanding from him is it will take 10-15 years to go through human clinical trials before something like this would be available to the public, and if the pharmacies did market it, it would be unaffordable for most people. This supplement has also been presented and published in several Neuroscience journals. Interestingly enough, Signum has been given more grant money from the Michael J Fox foundation to further their research. The research continues, and hopefully this product will help many people with cognitive and memory problems.
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That may all be well and good but I say it is a poor excuse to blame money issues for not doing true clinical studies of not just the EHT product but on the EHT molecule itself. By the way, PubMed is just the online library of peer-reviewed scientific journal articles. Here’s the general link http://www.ncbi.nlm.nih.gov/pubmed
People can say it helps them and that they can feel the difference. That’s great. But uhh, people say that a lot with placebos, something consistently demonstrated in real human clinical trials. I’m not disputing the in vitro laboratory and in vivo rodent studies. I really hope it does help people. What would really help them is not having it cost so much.
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The studies were very promising, I agree. There is an article in the white papers that explains the reasoning for distributing it before the trials were complete, and while I can’t say for sure, I believe they are being done. Now as for the cost, I hesitate to say this but this company gives away free product when their customers refer 3 people and they order something. I’m sorry, that sounds like a sales pitch, and it isn’t. I’m just passing along a fact about this company. There’s also quite a few of us who have given friends a box to use for a month at no charge, but like someone else said, best results are found after 90 days. Having said that, everyone is different and will have their own results with EHT. I do hope it helps many people also.
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MLM has NO business interrogating with people’s health. I can see how Nerium International can take itself seriously with the oleander based skin care product line. We’re used to that. But playing with someone’s health needs to sell product is bad business.
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Since EHT is a molecule of coffee, can’t I just drink coffee to get EHT?
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You’d get some for sure, but my understanding is the equivalent amount of EHT in one pill (35mg) would be found in over 200 cups of coffee. It’s a concentrated amount. I would have to do more research to find the source of that number though.
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That would be great if you could find that out! I could not find it anywhere. Thank you!
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Lisa is right. I don’t recall the numbers myself but yeah, the amount of coffee you’d need to consume is huge. One good thing about it is that it is still present in decaffeinated coffee. But you’d still need a lot.
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I have taken EHT for a year now. I will never be without it. It has helped me with so many things. Good sleep, fibromyalgia, memory, sugar cravings. My husband’s restless leg syndrome went away, he went off of it for 9 days and it came back. He said he will never go off of it again. Our granddaughter’s anxiety is better and no more panic attacks. Her focus is so much better she went from It does not cure anything but it helps many things. C’s and D’s to A’s and B’s in school. He love it. she is 15. and oh ya haven’t had any migraines since taking it, haven’t even had a headache and neither has my granddaughter. I’m 68 last year I felt like I was 78 this year I feel like I’m 58. Placebo or not I’ll take how it makes me fee. And yes I am a Brand Partner. I have a friend that has struggled with restless leg syndrome for years, actually two friends. They have been on every medication the doctors could put them on. They both have found relief with EHT. both feel it has been a God send.
Shauna
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Hi Shauna,
I think it’s great that you and yours have found something that works for you. So many people go through so many steps and try so many different things – and never find anything at all that helps them. Many drugs that are definitely going to fix your problems – nada. So many others that are just plain scams (according to various authorities) – wonderful results. Although the story is rarely so cut and dried sometimes a product is just the fit.
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Thank you Peter for your very thoughtful and logical summary. Do you have any updates on those medium clinical trials?? Also, the randomized trials 11a I believe in France by Vellas et al? I haven’t been able to find the article on line have you?? And what dose did they use? I recall 40 and 80 mcg? Or mg? This was EHT 2020 and if the dose is totally different from the EHT dose in nerium (35mg) how can we compare the two at all?? Allie
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Allie, It’s my understanding that EHT 2020 and EHT in Nerium are 2 completely different substances and should not be compared in anyway.
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Sorry, Allie. I missed that you commented on this regarding EHT 2020. Beth is correct. EHT 2020 is an actual compound, etazolate hydrochloride, that has gone through actual clinical trials. I don’t believe it has found widespread effectiveness in treating Alzheimer’s but I haven’t researched it lately. Regardless, it is an individual molecule whereas Nerium’s EHT is a mix of supplements.
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