Vitamin B6: Increase NAD Without NR, NMN, or Niacin?
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- Опубликовано: 15 апр 2023
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Papers referenced in the video:
NAD and the aging process: Role in life, death and everything in between
pubmed.ncbi.nlm.nih.gov/27825...
Vitamins and aging: pathways to NAD+ synthesis
pubmed.ncbi.nlm.nih.gov/17482...
Vitamin B6 and Diabetes: Relationship and Molecular Mechanisms
pubmed.ncbi.nlm.nih.gov/32456...
Substrate product ratios of enzymes in the kynurenine pathway measured in plasma as indicators of functional vitamin B-6 status
pubmed.ncbi.nlm.nih.gov/24004...
Age differences in vitamin B6 status of 617 men
pubmed.ncbi.nlm.nih.gov/941866/
Food and Nutrition Board, Institute of Medicine. Vitamin B6. Dietary Reference Intakes: Thiamin, Riboflavin, Niacin, Vitamin B6, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington D.C.: National Academies Press; 1998:150-195 
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For those wondering how the B6-NAD experiment is going, here's the most recent data!
ruclips.net/video/8FtLyAfaY9Y/видео.html
Hi have you done any study or experiments with THC or CBD in relation to aging? I would be interested in these if you have any comments or views.
Not yet @@MRT-co1sd
When I see you review pathways like this to potentially boost NAD, it makes me realize just how complex the human body is. Keep up the great work Michael as it is highly interesting to follow!
This is the best presentation of a biochemistry topic I have seen for those of us who studied a little bit of biology. You explain a complex topic without dumbing it down. Please keep up the good work.
Thanks kenhnsy, and will do!
COMPLETELY AGREE! Now subscribed
Same 😊
@@conqueragingordietrying1797 Have you looked into the safest form of vitamin B6 and if it's still available? Back in 2009, articles started coming out saying the FDA was working to ban the safest form of vitamin B6. The form that doesn't build up and cause nerve damage. I believe it's pyridoxamine.
The FDA was trying to protect the investment of a drug company using it for a new drug;
"A North Carolina-based firm called Biostratum began manufacturing pyridoxamine-based drug called Pyridorin designed to prevent the progression of diabetic nephropathy (kidney disease)."
I'm not sue if the FDA got away with it or not.
@@conqueragingordietrying1797 B6 is NOT the answer. It easily builds up to toxic levels -- even at low doses -- and that 'toxic' level has been lowered to 20mg/day in Europe. Also, B6 increases levels of the toxic metabolite quinolinic acid: adc.bmj.com/content/archdischild/41/220/652.full.pdf
Wow this is great Michael! You have cracked a new shell on the road to the Conquest! Congratulations and Thank you for all your hard work ❤️.
Your videos are perfect. I love everything about them. Can’t wait to see how this turns out.
Thanks Michael Zumpano!
Can’t wait to see the results from you ❤
Really hard work. Thanks for this informative video.
Absolutely excellent. I've been preaching about B6! It is indeed, amazing.
Excellent analysis!
SO interesting, informative, and useful. Thank you for what you are doing here!
Thanks @mathewdallaway!
Wonderfully explained fluid and comprehensive, thank you so much,
Precise, methodical, excellent. Thank you.
If you can't explain it simply, you don't understand it well enough.
Albert Einstein
You, Dr. Mike embodied this quote 👏🏽👏🏽👏🏽
Looking forward to your test results
Great presentation
Great video
Interesting, first vid of yours i've watched. Catchy name too.
The literature also suggests that exercise is a modulator of Kyn, but in your case, Michael, you've probably already optimized exercise and you're not that old. But wonder what the age vs KYN graph would look like for exercised older people vs general population.
It plays a role in everything from the Alpha Ketoglutarate pathways, to Glycine cleavage pathways to, to Amino Acid Metabolism, to redox reactions involved in the NAD+ to NADh, NADp to NADph, and FAD to FADh pathways; the processing of carbs, fat, and protein.
Its a universal puzzle piece. A joker card.
Sadly, the health and regulatory authorities add a synthetic version to all our foods which is rate limited, and will give you neuropathy if you take enough to meet all your needs - especially with all the excess sugar in our diets.
The P5P variant is essential.
Its not the core dysfunction in NAD metabolism, though. You are missing a slave ossilator of circadian rhythm and epigenetic quality control, plus mitochondrial complex 1 to 4 dysfunction.
P5P is one of the keys, though.
You might not have realized it, but you have found a way to help Aryl Hydrocarbon Receptor Dysfunction we are all suffering. One of the core dysfunctions is in the Kynurenine pathway. The others... will take more explaining.
I'm working on patents, so sorry I have to keep my mouth shut for once on more about the Aryl Hydrocarbon Receptor.
Is it tge sane one that takes advantage of how body switches from Oxphos to Glycolysis and back? You are my favorite utube commenter luv ur puzzles 😉
@@Always-xl9db Its one of 4 key dysfunctions in cellular NAD metabolism, yes.
Electron donors and electron acceptors. How does their metabolism change when in Oxphos vs Glycolysis, and how does that relate to reductive stresses.
A little hint for those smart enough to seek answers.
It's fascinating, but things get more complicated if you are not from this niche. So basically you suggest sleeping on time and taking the P5P variant of B6 as a start :)
@@unknmanserbia2642 Sleep helps balance out reductive stresses.
Research the impact of Nocturnin and Melatonin on NAD Metabolism and NOX4 expression, tryptophan metabolism, IDO expression, etc.
Those werent the pathways I was discussing here, though.
One could consider that a 5th pathway outside of the 4 pathways I've already discussed about NAD metabolism dysfunction.
Blue light exposure and lack of sleep.
…and Phosphatedylserine too, take it as well
Excellent....!!!!
Great Video with data and explanations! Referring to your 3X increase in B6 intake, from all the stuff I ve read about vitamins in general and my personal experience with taking 10000IU of D3 daily, it seems like the RDA's are to be understood as minimal levels for survival, whereas we all are looking for the levels that lead to optimal health. And these are 2 completely different things. Im not a doctor I just read alot, so if any doctor can comment on this, I d love to hear thoughts on this.
Thanks Angel. I definitely agree about the RDAs being a minimum. How much is optimal for health and longevity will then be highly individual, and blood testing will be essential to that process. That's a central premise of this channel, to test!
Thankyou for trying this out.. Please update us
Thanks CryptoPhil Phil, will do! I expect results and an update video sometime in early-mid May.
Impressively clear and concise presentation. Best I've seen. I take levodopa/carbidopa for Parkinson's, and the carrbidopa kills B6. I've just taken some B6 (50mg P5P) - hoping for a bit of a lift in energy level which has been low...
I put Carbidopa and B6 into chat gpt, this is what I got:
Carbidopa is often used in combination with levodopa to treat Parkinson's disease. Levodopa is a precursor of dopamine, a neurotransmitter that is depleted in Parkinson's disease. By increasing the levels of dopamine in the brain, levodopa can help to improve movement and other Parkinson's disease symptoms.
However, when levodopa is taken without carbidopa, it is rapidly metabolized in the body, leading to high levels of dopamine in other parts of the body and potential side effects, such as nausea and vomiting. Carbidopa is used to prevent this peripheral metabolism of levodopa, allowing more levodopa to reach the brain and reducing the risk of side effects.
Pyridoxine, also known as vitamin B6, can affect the efficacy of carbidopa-levodopa therapy. Pyridoxine can increase the peripheral metabolism of levodopa, reducing its efficacy and potentially increasing the risk of side effects.
Therefore, it's generally recommended to avoid high doses of pyridoxine while taking carbidopa-levodopa therapy. However, small amounts of pyridoxine are usually safe and may even be beneficial for some individuals. It's important to speak with a healthcare professional about the appropriate use of pyridoxine and other supplements while taking carbidopa-levodopa therapy.
@@Dedicated_.1 Well yes exactly, the carbidopa is lowering B6 levels every time it is taken, so it would seem a no-brainer to top up B6 ocasionally (before bed for minimum overlap with the PD medication).
I did indeed feel a bit of a lift this morning from taking some B6, but I'm hoping for more from big doses of B1, as proposed by Dr Constatini and as featured in several videos on EONutrition. Still waiting for the B1 to arrive though, but fingers crossed.
@@pjkkerr I just mentioned the chat gpt result because of the 3rd paragraph on risks of taking pyridoxine. You may counteract the effects of the Carbidopa, and cause peripheral metabolism that Carbidopa is designed to avoid.
Perhaps your levels of pyridoxine at 50mg are small enough to not have this bad effect but just to give you the heads up!
@pjkkerr Instead of taking high doses of thiamine hydrochloride because of poor absorption, consider taking allithiamine with food
@@IncreasedAngerPill Or the injection form of thiamine HCl to bypass the digestive tract
This class of yours was masterful!
I take advantage of your generosity to ask if B6 is also important in histamine breakdown?
Thanks Gionei. Unfortunately I haven't studied it (yet)...
@Dr. Gionel G. Silva @Conquer Aging or Die Trying! I also appreciate the information presented here. So here is a quick snip re B6 from an article on histamines: Vitamin B6 supports DAO production, but it also increases histidine decarboxylase (HDC), and may, therefore, increase total histamine production. Generally speaking, this vitamin is required for a healthy histamine metabolism.
Interessante!
Given reports online as to some B6 supps being scams (no niacin in them!) I am confused as to which product to try. Also confused about which version as I would like to adjust my LDL and HDL which are skewed the wrong way!
Age increase acetyl carnitine ?
Thanks for update Michael. Great graphs and diagrams as makes easier to fully understand. Have read much in other studies that much of supplements like nr and nmn do raise nad but many saying just in blood cells. Not sure if NAD though is raised in most important cells of brain and muscles. All cells effected differently. What have you found on this for more than just blood cells? Thanks
Thanks Michael. it will be just for blood cells, but that's a good start, imo.
Yes, NAD+ levels are increased in brain through NMN oral supplementation if this is what you are wondering about. At least it’s been shownin animal studies
@@Always-xl9db thanks for this update. Wonder if did too in animal muscle cells? I do many 5k type charity runs - maybe 20 to 30 per year for past 40 yrs. And log 15 to 20 miles jogging each wk. Have tried so many supplements for improvement on my 5k charity race times. Track closely and seems nothing helps month to month for improvement. And too each yr my 5k times keep dropping on steady basis. In 60s now and is old so maybe the reason. Seems in the 3 lab at same time (non profit intervention testing program) with mice the one of few of many substances showing improvement for age slowing was rapamycin. Not much else. Maybe need to contact the one of few docs (Alan green) in ny to see if can get prescription for rapamycin
Rapamycin is all about mTor suppression so if you are an athlete and want to improve results that seems counterintuitive.
@@michael-qp9xd Have you considered CoQ10 ( CoEnzyme Q10). I had a heart attack in 2009 that resulted in an estimated 20% damage to my heart. As usual I was put on Statins and a friendly Pharmacist suggested I take CoQ10 for 2 reasons, the statins drain it (and much more) from the body, and it supports muscle health and development, and the heart is basically a muscle. He also stated that HE believed that the heart does mend itself, but very slowly (2 % per year). My annual checkups continually showed some heart damage for around 7 years, then no damage was in evidence. I threw the statins away long ago as the side effects were disgusting but continued with the CoQ10 as I also found it provided additional energy for the day as well as supporting muscle health. As your racing obviously asks much of many muscle groups it may be worth researching CoQ10's value to such an endeavour.
What about B1 thiamine? esp TTFD
Are you getting the additional b6 from food? I assume it is in pyridoxine form not pyridoxal, as I've heard most food has b6 in pyridoxine form. I'm tempted to increase b6 too, I was taking just rda levels from a multivitamin. Solgar sells a nice 25mg version that seems to have reasonable amount without approaching the upper limit, will probably get that.
Hey Diamond S, I wish there was a way to get 10-15 mg+ from food. I'm supplementing with pyridoxal phosphate powder, not pyridoxine, which is 2 enzymatic steps from conversion into pyridoxal phosphate-that's the B6 isoform required in the tryptophan-NAD pathway.
you can cut the 💊
Does the NMN supplement interfere with carbadopa like b6?
Nope. Carbidopa binds to B6 (P-5-P). It has absolutely nothing to do with NMN or any other vitamin.
I apologise if I missed it, but...
Do you have any content on anti aging of joints for example reversing osteoarthritis?
Do you have any videos on collagen supplementation, forms such as UC-ii and more common types such as 1 and 3?
What is the mechanism of action and optimal dosing for joint health, skin and bone and/or muscles?
Hey Little Voice, unfortunately not for osteoarthritis. Nope on collagen supplementation either, but that may change at some point, as there seems to be promising data in terms of skin health.
@@conqueragingordietrying1797 I myself think that activating Autophagy, say once a week, is likely to be helpful…
Just my 2 cents, I take Curcumin (the active compound in Tumeric) for ulcerative colitus having found the usual drugs had massive unwanted side effects, it's proved very effective as an anti inflammatory and is supposed to assist in joint health. As a side benefit it also rid me of my Fibromyalgia, eased my joint pains, and seems to have improved my skin. As it doesn't require a prescription and is not expensive it's been a real blessing to me. I'm a 73 y.o.male in Australia.
Hi Little Voice, I had ongoing problems with my knees for years, and tried many different possible solutions. In my own subjective experience, curcumin (plus piperine) supplements do noticeably reduce the inflammation and pain.
However, I seem to have recently 'cured' the issue almost completely, not just fixed the symptoms. How that happened is not entirely clear to me, but it seems to be associated with my supplementing magnesium daily, and taking liposomal fisetin (1000mg, together with 200mg quercetin, one or two days per month max).
I have also added 20g of dried parsley and 25mg zinc daily to my diet, but I don't think those have influenced my knee pain necessarily, I'm just mentioning them to give the full picture of my supplements. I'm 45, and started having issues about 10 years ago.
what dictates tryptophan going down the NMN pathway vs the melotonin to serotonin pathway. What will lean which way or the other?
From what I've read, the majority 95% goes to NAD synthesis, with < 5% to melatonin. I'm not sure about regulation, though, that's a great question, especially since it's not just these 2 pathways-tryptophan is also metabolized by gut bacteria into indoles.
@@conqueragingordietrying1797 thanks for the info.
Most b6 i see are 100 or 250 mg. Am i reading something wrong? How are you getting your dosage right?
I skipped the pills because of fillers, and bought PLP powder instead. I made a B6 solution with 1g in 200 mL of water-then, I take a 1-3 mL aliquot of that every day.
nice work, Michael!
I really wonder how those RDA levels came about... historically, not knowing anything, taking the average of a mal-nutritioned population, condensing gradually from wild guess int pseudo factual myth, i guess.
Good point. The basis of RDA development is never mentioned and is vital to understanding everything else.
How am I ever going to quit my daily lo carb monster when it has niacin and b6?
Ah, Monster contains pyridoxine, so it's 2 enzymatic steps away from conversion into pyridoxal phosphate, which is the form of B6 needed to overcome the potential block in the tryptophan-NAD pathway.
Why would B6 reduce in aging assuming that there is no change in diet, and why wouldn't supplementation be likewise blocked?
Great question, thanks David.Inflammation mat be one reason for why blood B6 can be degraded during aging:
pubmed.ncbi.nlm.nih.gov/34117761/
pubmed.ncbi.nlm.nih.gov/31129702/
With that in mind, reducing systemic inflammation would be the primary goal, but in my case, hsCRP is low (< 0.3 mg/L), so it may simply be suboptimal dietary B6 intake.
What kind of B6 did you take? Pyridoxine or pyridoxal phosphate?
Pyridoxal phosphate
So does this mean B6 supplementation is just as good as NR or NMN for NAD boost?
We'll see, especially after the next NAD test, where my B6 level will be > 2x my current intake.
So meat has both tryptophan and B6 (and Niacin) so wouldn't eating meat boost NAD if this was the case?
That assumes that we can get enough B6 from meat (or any other food) to overcome a potential age-related block in that pathway-I'm not sure that's the case. Also, too much protein may have other adverse-health related effects on lifespan, as methionine restriction extends lifespan in rodents. That said, there's likely a U-shaped curve for protein intake in this equation, with too little and too much being suboptimal.
@@conqueragingordietrying1797 I don't think you can really use rodents as a good test subject for a meat-based diet. Humans have been hunting big wild game for millions of years. We're apex predators and have adapted to that kind of diet. We should be using lions or wolves to test diets on.
Would be awesome if he found an alternate way to increase NAD
I'm testing NAD levels on 4/24, so we'll know soon after that if B6 can raise NAD. Even if not, assuming no other biomarkers go crazy with ~10 mg of B6/d (and serine), I'm ok with going higher for B6.
So I looked at the amount of B6 in my multi-B vitamin pill = 5 mg. Then I looked for B6 on the supermarket shelf. The was only one brand and one B6 dosage =100mg, the max. 0mg tryptophan in 20 grams of the collagen supplement.
Most multivitamins contain pyridoxine, which is 2 enzymatic steps for conversion into pyridoxal phosphate, the form of B6 that is required in the tryptophan-NAD pathway.
@@conqueragingordietrying1797
B-Complex capsule
Pyridoxine Hydrocloride 5 mg
B-6 capsule
Pyridoxine Hydrocloride 100mg
B6 should help reduce homocysteine, right?
In combination with serine, yes, and I'm also currently supplementing with that.
Thx prof! As always great content! On a different note, i would like you to review and comment Bryan Jonhson blueprint please. He is rising fast in the conquer-aging community, he almost look 20 but he's aroung 60 and he claims he is aging at 0.75y/year. Is he the next "liver king" of the conquer-aging community or is he legit?
Thanks Antoine. Bryan's doing a lot right in terms of attempting to quantify as much as possible. His DunedinPACE data is legit (0.69 for one of his most recent tests, which is currently better than mine).
@@conqueragingordietrying1797 Thanks! I appreciatr it!
Bryan Johhson is only 45 years old and he looks every minute of it and more.
Epic
so you said that increased B6 will increase homocysteine, but it is bad?
I must've misspoke if I said that-B6 in combination with serine should reduce, not increase homocysteine.
Question, is Pyridoxine HCL form count?
Pyridoxine is 2 enzymatic steps from conversion into pyridoxal phosphate-that's the B6 isoform required in the tryptophan-NAD pathway.
@@conqueragingordietrying1797 thank you for your reply, I take a B-12 + B-6 supplement from the brand Cymbiotika. Per serving it contains B-6 (Pyridoxine HCL), L-Methylfolate, B-12 (50% Methylcobalamin, 25% Adenosylcobalamain, 25% Hydroxycobalamin). I am wondering if I should consider ordering the pyridoxal phosphate aswell to add to my stack and if you have a recommended brand.
You said you want to increase homocysteine but isn't elevated HS a marker for elevated risk of heart disease and stroke?
No, decrease homocysteine. If I said increase, I misspoke.
Hi there, when are the data about your NAD coming up?
The sample is still in transit, USPS is terrible. I mailed it on 4/24.
@@conqueragingordietrying1797 it would be really fascinating to see how vitamin B6 in a dose higher than WHOever recommends affected your NAD levels!
Not to forget that higher doses in Vitamin C and D have been found to fortify the immune system and detoxify the body in a really effective way, for many rather salvationing during pandemic. So I keep hopes that significant results may come on B6, and if not on NAD, perhaps on other health aspects!
@@dancingverum I totally agree, and even better would be if I can increase DHEA-S (which requires NAD(P)H for its synthesis) as a "side effect" of that process, too.
Since 4/24, I've increased my B6 levels to 30 mg/d (up from 11mg/d), so I may test again quickly once I get the 1st results back for NAD.
Where does niacinamide fit in to all this? 🙏🏻
When considering that niacinamide increases homocysteine more than nicotinic acid, not yet...
pubmed.ncbi.nlm.nih.gov/27567458/
How do you know these things convert in the body? Where is the evidence? Is this all hypothesis or is it legit?
I sent blood for NAD analysis on Monday, we'll see if it's legit soon...
I used NMN to increase my NAD and I used Fisetin to lower my CD38
does fisetin lower cd38 too? i thought it was apigenin that lowered cd38
While NMN increased my NAD from 25 to 39 uM, I'm not convinced I addressed the underlying issue, which may be suboptimal B6 status and reduced efficiency of tryptophan's conversion into NAD. We'll see if that's true in a few weeks with NAD testing.
@Conquer Aging Or Die Trying! if you don't take enough NMN then you are just playing around.
@@luckssj Did you watch the video?
I might as well take a high strength multivitamin and mineral supplement at this point. Health is so complex
Michael-after realizing that there are too many gaps in my knowledge to adequately follow this presentation, I scanned the playlists, looking for an obvious primer series, but couldn’t pinpoint a list that might fit the bill. Is your content meant only for people with a pre-established base of physiology/pharmacology knowledge? Or is there a relevant on-ramp within your uploads that doesn’t require watching every video from inception? Earnest question.
Hey Dusty, the videos are meant for everyone. If it's hard to understand at first, I'd suggest rewatching a few times, looking up concepts that may be new. That's my approach for new info, too...
Hey Dusty, I understand how some of Michael’s videos could seem confusing, it’s because he’s been on this journey for a while now, so imagine his videos like any good TV show series, there’s a lot to catch up on. I will say once you do, Michael’s done a great job of explaining his path so that anyone can follow it. He’s literally the Neil Armstrong of Anti-aging.
Well said and thanks@@LandonPark!
Thanks-I did a deeper dive and now I’m up to speed. Very unique and helpful videos you have here. I’m looking forward to them.
I also no native english speaker, so Im trying to follow all this new words, like Im looking for pyridoxal phosphate supplements but I only can find P5P, and I dont know if that could work
Well what happened? Did the increased by help?
That video was released yesterday!
ruclips.net/video/8FtLyAfaY9Y/видео.html
I just learned this morning that B-6 is also vital for calcium absorption and started taking it. The capsules are 100mg though so I might just take it once or twice a week...
Edit: I just realized as well that the first time I took B-6 I immediately began lucid dreaming, which is also the same thing that happened when I first started taking Nicotinamide. This pathway seems to indicate that they do indeed have similar if not the same effects.
any thoughts on Nutritional yeast?
To get around the dosages in capsules, I bought PLP powder, and suspended 1g in 200 mL of water-then, I'm taking small aliquots (1-3mL/d) to get ~10 mg/d.
I take about 1/3 to a 5th of a 60mg tablet of the p5p form of B6. I cut them, but the daily dosage is variable because my cuts of the tablets are variable.
@@conqueragingordietrying1797 I use 2 tblespns of Nutritional Yeast on my sauerkraut daily for full B complex. Not as measured as your approach , but well above DV%.
Thorne got 33mg capsules of p5p…I take half of it.
May I ask which brand you use for your supplements?
For serine + B6, bulksupplements.com
@@conqueragingordietrying1797 wich one Pyridoxal-5-Phosphate (P5P) or Pyridoxine Hydrochloride?
is it the same L-Serine than Serine?
@@Am3gari I'm using P5P
@@conqueragingordietrying1797 thanks
haha, conquer aging or die trying
Mike Lustgarten, is that you?
Yes Paul, it shouldn't be a surprise, I've been doing this for ~3y
This implies that for most of the population: redbull supports their NAD levels.
Ah, it's a different form of B6, pyridoxine which is 2 enzymatic steps away from conversion into pyridoxal phosphate.
Dude. Way too complicated. I’m glad some folks enjoy this, I just don’t like to have to have a biology degree or course in order to sit through and listen to what the point is. Sorry man.
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Unfortunately, they don't ship to Russia atm
@@conqueragingordietrying1797 IN the futurec obtain Russian made anti aging Supplements they are superior n more advanced than Amerikan supplements Yuliya 🇷🇺✝️
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So, stick with carnivore. Got it!
you should be more careful discussing B6. If people get B6 supplements they are ususally much more than needed and can permanently damage nerves.
The tolerable upper limit is 100 mg/d, which is discussed in the video. Going higher than 200 mg/d has associated with neuropathy, as you mentioned.
@@conqueragingordietrying1797 The tolerable upper limit its not reliable because everyone is different. For exemple you can have a functional b2 deficiency (this require selenium, molybdenum and iodine) and not converting b6 to its active form this can cause a b6 toxicity even at low dose, if you are low in aldh (because of low nad+) and low molybdenum you can get aldehydes poisoning because pyridoxal is an aldehyde.The mere fact of basing yourself on it shows that you are not very well informed...
@@rayquaza6791 A big focus of this channel is testing to identify how much (or not) is required, which often goes beyond the RDA.
If you think I'm uninformed, unsubscribe.
b6 dose?
A small increase with 12 mg/d
i dobt think it will work. i was taking 500mg to get some sleep/dream benefits… b vitamins dont give you sideffects but if you want therapeutic effects then 13 mg is just pathetic imo@@conqueragingordietrying1797