Possible negative response to oral NAD+

Hello,

    My wife and I (~50) have started a NAD+ regime in addition to rest of the other life long regime (vegan, exercise, other suppls). We started with 250mg (sourced from Life Extension), and after reading research from Elysium Health we upped the dosage to 2x250mg in the morning. 

     We both experienced the usual effects, namely deep sleep/dreaming, but after some weeks my wife started to have negative effects. Started with her legs, a feeling she couldn't describe, but was something like 'restless leg' syndrome kind of thing it sounded like. Then she started to get more and more agitated, and while out shopping almost fainted on getting out of the car on at least two occasions. Suspecting the NAD+ she discontinued taking it and immediately went back to normal. I haven't had any negative effects, but she does tend to be more sensitive to foods/supplements/etc than is generally the case. 

     This isn't proof of anything, and we're considering having her start up again but at the 1x250mg dosage and seeing how it goes. Searching the web brings up precious little, there is a discussion forum where some people talk about this possibility due to 'over methylation'. Just a post by somebody so no backup on this, but I'm posting here to see if anybody has any thoughts on this. 

 

Thanks -

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  • Thanks Dan, good to know.

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  • If not already doing so, I would add magnesium and vitamin D3 to your regimen. My wife too seems to be sensitive. She gets mild headaches and feels tired soon after taking her supplements. Since I added carnosine and benfotiamine to her supplements, she seems to be doing a lot better. We take NAD, jiaogulan, PQQ, benfotiamine, carnosine, methylene blue, Ashwagandha, astragalus, Senolytic Activator, rapamycin, metformin, vinpocetine, pterostilbene, ubiquinol, Magtein, etc.

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  • Hi Dean. This is an impressive list! Regarding the vinpocetine, have you noticed any effect on your hearing?

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  • Dan, the more I've looked into increasing NAD+ levels, the more I've come to prefer NMN over nicotinamide riboside.  It seems to be a lot more effective at actually raising NAD levels.

    Having said that, I do still supplement with both since they work through different pathways and I want to cover all my bases.

    One thing to note is that there is some concern about the potential for methylation issues here.  I take a TMG (trimethylglycine) supplement to compensate.  See https://chrismasterjohnphd.com/lite-videos/2018/07/26/careful-niacin-nicotinamide-riboside/ for more info.

    Also, if you're taking Elysium, there's more than just NR in there.  It may be one of the other ingredients (I think it also has pterostilbene in it?) causing you problems.  I generally just go for straight-up NR.  I get mine from LEF and I've had no problems with it.

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  • Ive never liked NR or NMN. It seems like snake oil. I do feel Niacinamide is worth having just for the extra protection from skin cancer. 

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    • Richard Sapp Why snake oil?  Both seem to work and have well-understood mechanisms of action as far as how the body converts them to NAD.

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  • Ive spent years researching anti-aging. It was by accident that I discovered how tightly woven energy production and the immune system actually are.  Ill always feel negatively towards NR and NMN. Chromadex, Elysium, and Dr. David Sinclair are, in my opinion, fraudsters or close to it. There needs to be numberous peer reviewed studies published through the N.I.H. before I will consider either product to be more effective than niacinamide alone. Do we even know what the bioavailability of either product is? How long does it work in the body? How long does it need to work before we see a net positive change? What has been changed and for how long? 

    The people behind these companies have charged out here like theyve discovered the fountain of youth. I vehemently disagree with any such similarities. 

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  • From my own research - I've been working as a biochemist for 35 years - I'm aware of both positive and negative responses to oral NAD+. The negative responses seem to be mostly minor and resolve upon discontinuation of the supplement.

    I started taking nicotinamide riboside (NR) in Oct. 2016 at my son's suggestion. (These days he's also a biochemist and works in CBD research). I was surprised to discover that after several weeks of consuming NR, I no longer needed as many beta blockers as before to control my atrial fibrillation. I later heard from a leading telomerase researcher that he had also gotten considerable relief of AFib from taking NR. Subsequently I fermented an oral NAD+ product with greatly enhanced bioavailability and have been taking it ever since in lieu of NR. Data from the cardiac clinic at roughly 6 month intervals show that my incidence of AFib decreased from 4.6% of the time to 1.7% to <1% to <0.1%, where it leveled off. A literature search revealed a probable mechanism: AFib is typically associated with mitochondrial dysfunction in cardiomyocytes, which can evidently be ameliorated with intake of NAD+. As a result I was able to decrease my consumption of medication from 7 pills a day (100 mg of beta blockers t.i.d. plus 120 mg of a calcium channel blocker) to just 2 pills (50 mg of beta blockers b.i.d.).

    That's the positive news. There were other benefits as well. My NAD+ formula did a remarkable job of reducing painful inflammation in my hands, arms, and shoulders. I could also track the same results with blood tests showing decreasing levels of CRP and ESR (sed rate). Also, my son has been taking the product ever since and claims that for him it's been a more effective antidepressant than SAMe.

    The downside of both NR and my formulation is that anything that functions as an antidepressant is potentially anxiogenic and can interfere with sleep. A friend of mine, a molecular biologist at Tufts Medical School, found that he couldn't tolerate a single 250 mg dose of NR because the resulting anxiety drove him up a wall. My girlfriend and several other people can't tolerate either NR or my formula because a single dose keeps them up all night. Fortunately this reaction seems to be relatively rare. I also noticed that any mild insomnia I initially experienced quickly disappeared as my body got used to the product. For several years I've been able to take substantial doses just before bed without adversely affecting sleep.

    One other comment about negative effects: a friend of mine was consuming 125 mg sublingual NAD+ b.i.d. until a blood test revealed that she had developed leukopenia (deficiency of white blood cells). Her physician recommended that she stop taking all supplements and the condition spontaneously resolved. It seems likely that excessive intake of NAD+ was the culprit, especially in view of the following paper: https://www.ncbi.nlm.nih.gov/pubmed/31053044.
     

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      • BobM
      • BobM
      • 2 yrs ago
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      William Sarill 

      excellent post!

      Thanks for sharing!

      Your NAD cocktail has me curious. Can you please describe further?

      thanks

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    • William Sarill 

       

      Thank you for your interesting and insightful contribution. I wonder if you have other experiences you would like to share. Experiences related to supplements that are supposed to promote good health, wellbeing, antiaging or treatment/prevention of disease. it is always very intresting to hear case-studies like the one you described above. 

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    • BobM 

      Briefly, I developed a fermentation technology that uses off-the-shelf probiotic bacteria to generate a range of mitochondrial agents and cofactors. The products include coenzymes, nucleotides, amino acids, osmolytes, and antioxidants, all with enhanced bioavailability compared to conventional forms. One such product is a form of NAD+.

      For testing purposes I make up samples from sterile filtrates of probiotic cultures. The easiest way to do this is to subject food grade liquid probiotic solutions to the proprietary process I discovered, then centrifuge and sterile-filter the supernatants. I've also cultured yogurt using the same process and freeze dried the resulting whey for the sake of stability. And finally I've made sauerkraut using L. plantarum naturally present on cabbage leaves. In each case I was able to get the microorganisms present to generate a potent, orally bioavailable form of NAD+. The biosynthetic process is robust in the sense that almost any probiotic culture will suffice.

      I can't provide more details right now, but I can at least give an idea of the thinking that inspired these discoveries. My work lies at the intersection of nutrition, mitochondria, and the microbiome. We know that animals co-evolved over a half a billion years in symbiosis with microorganisms. On the other hand mitochondria are themselves thought to be remnants of ancient alpha proteobacteria that were incorporated as symbiotes into primitive cells. It is no accident that mitochondrial nutrients - such as B vitamins, amino acids like taurine and GABA, and antioxidants like melatonin and glutathione - can be synthesized by probiotic bacteria such lactobacilli. Furthermore, microbiome-mitochondrial communication is a well established fact. I have reason to believe that the fermentation process I developed mimics a natural mechanism for signaling among cooperating bacterial species and mitochondria as well.

      To put it another way, the cornerstones of optimal health are proper nutrition and a healthy microbiome. Each, however, is incomplete without the other and both are necessary for proper communication with mitochondria. By steering probiotic cultures to create "pre-digested" nutrients, it's possible to generate nutritional forms that are optimally adapted to support mitochondrial function. 

      As an example, I brewed a stable form of AICAR (natural activator of AMPK) that is orally bioavailable, unlike conventional AICAR. The situation here is similar to that with (conventional) NAD+, which gets broken down by brush border enzymes of the small intestine. I formulated an orally active product containing NAD+ and AICAR-like ferments, together with another nucleotide. A collaborating physician provided it to several subjects with post-Lyme syndrome. Marked improvements in fatigue, detoxification, and immune status were noted in 6 out of 6 subjects. My sense from this and other work is that the body can heal itself of virtually anything if given appropriate mitochondrial support.

      I'm putting together a company (supraBiotics) to develop and market such products. It's going slowly because I need additional test data and more funding. At some point I'll post a more detailed description of the nutrition/microbiome/mitochondria connection on my suprabiotics.com website, which is otherwise empty of content at the moment.

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    • Staffan Olsson 

      Yes, I have other observations I can share when I have time to respond. Thanks for your interest.

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      • garland
      • garland
      • 2 yrs ago
      • Reported - view

      William Sarill Hello there... Sounds like you are on your way to making a huge contribution to all of us seeking aging reversal. I was wondering since I have AFIB and it seems to be rather permanent but I am controlling it somewhat through Meditation and tapping on Acpupuncture points which seems to help. I also take some aspirin and Nattokinase and a whole host of other nutrients including 500 mg NAD from Life Extension. However your findings intrigue me about AFib..... Would taking NAD from Life Extension help this?  Right now it does not seem to help much. I do take Pterostilbene to help it get more assimilated in the body. But maybe the patches would be better? Would NAD from Life Extension be the same as NR? Thanks for your time.... keep up the great work and hopefully you will have a break thru soon....

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  • I have been  taking a NAD booster with amazing results. I have been taking it for two years now. I had more dramatic results since taking a double dose. My hair has gotten thicker and even more energy now too, skin improvements as well. I also have my dog on it too and she is going great at 16. I think it has extended her life in my opinion. We both take a telomere supplement as well. I am excited as I am soon taking a senolytics product new to the market. It is being formulated now. They are having issues getting the last ingredient to make it. They said its hard to find someone that makes the ingredient needed in the concentration to be effective. Anyway very excited as I will be giving this to my dog too. Hopefully, she can make it to 18 years or beyond. She is a black lab. 

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      • CK
      • sapphire_cactus
      • 10 mths ago
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      katie larking Hi, can you please share the telomere supplement you are taking and details of senolytics product you are referring to ?

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    • CK yes please email me info@betterhealth4you.net - I dont want to promote brands online

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  • Hi, I started adding Resveratrol to my morning TruNiagen 300mg pill and the side effects are in my case problems breathing, anxious, quite altered. Not sure if anyone had a similar experience.

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