> Vitamin B12 deficiency can cause PGH through unknown mechanism. About 55% of patients with pernicious anemia had graying before 50 years as compared to 30% in the control group.[32]
/soapbox
Get your B12 tested (before taking supplements!).
B12 deficiency is known to present in many ways, and also to be often overlooked in clinical settings[1]. It’s known that not everyone presents with the anaemia from it[2], which is often why it’s skipped as a diagnostic option. Additionally, long-term/severe deficiency can present with symptoms almost identical to multiple sclerosis[3]. Deficiency of other B vitamins, such as B2, can cause a functional B12 deficiency as well[4]. It’s also known that supplementation will falsely elevate levels even in the presence of a deficiency.
The paradoxical B12 deficiency might have a relation with the inactive form being supplemented. If one supplements cyanocobalamin, and one expects the body to convert it to methylcobalamin, and if this conversion doesn't happen for whatever reason, and if the measured form includes the inactive form, then "paradoxical B12 deficiency" can be observed.
There is a more insidious form of it whereby the active form doesn't enter the brain. Symptoms are: difficulty speaking, tremors and ataxia. This can be tested by CSF (cerebrospinal fluid) testing. This assumes that the active form is supplemented and it is present in blood. It can be remedied by a course of corticosteroid pills, followed by megadosing B12 orally daily. Refer to PMID 38924428.
I take a triple active form of it which is methyl+hydroxy+adenosyl, covering all bases, but a total of just 500 mcg per day, above which it harms my sleep.
Would you mind sharing a brand or a link? I have had grey hair since I was in my 20s and struggle with energy. I have been taking nature made multi vitamin for a vitamin b deficiency that was high enough to cause craggy edges on my tongue, caused by the stomach acid suppressant I was prescribed. I would like to compare.
> The paradoxical B12 deficiency might have a relation with the inactive form being supplemented.
Yup, not everyone can convert cyanocobalamin or hydroxocobalamin to adenosyl-/methylcobalamin. Especially in severe cases, anecdotally I’ve seen people not make progress with the standard cyanocobalamin injections, but then make huge progress with methylcobalamin injections. Unfortunately, methylcobalamin is often not preferred in injectable form due to very quick degradation into hydroxocobalamin upon exposure to light.
Taking methylcobalamin B12 supplements essentially fixed my memory problems. Early on I tried out the cyanocobalamin type and got absolutely nothing from it.
If I stop taking the supplements for a few weeks, the memory problems come back. If I start again, a week later my memory is excellent. It’s well worth the minor effort.
What kind of memory problems, could you expand? I wonder if I fall on this bucket. I had graying hairs as soon as I finished high school (~19). One of my major problems with studying was an inability to retain stuff in university, which is weird because through middle school a single read was sufficient for me to retain stuff.
Mostly noun recall. I can mentally picture and describe thing or person X, but when I'm having the problem it could possibly take me 30 minutes to figure out the name of X without looking it up.
Subligual methylcobalamin works just as well as the shots and you can buy it anywhere.
Also, get a Methylmalonic Acid Test with you B12 levels. An MMA test is more useful because it is an enz=yme which uses B12, so when the active form of B12 is low, so will MMA in most cases.
> Subligual methylcobalamin works just as well as the shots
It does not. The cobalamin molecules are quite large and don’t penetrate the sublingual mucosa very well. On top of that, the proteins in saliva that bind to B12s will cause any bound B12 to not absorb sublingually, instead having to wait to make it through the digestive system for intestinal uptake.
Sublingual is still certainly a better option than oral pills, but the injections are preferable in severe cases for a reason.
There's no risk in non-smokers if you stick to a sane dose. Megadosing it can harm sleep and severely increase blood pressure and heart rate, although these gradually reverse upon cessation. This can take time to manifest. It is why I limit the dose to 500 mcg per day. Older people, such as those over 70, can need more and tolerate more, even 5 mg per day, due to deteriorated absorption.
Also, don't forget the other B vitamins. In truth I take them all.
> There's no risk in non-smokers if you stick to a sane dose.
Also, B12 is water soluble, which generally means that your body is pretty good at flushing out any excess it can't use, making it difficult to overdose on. (Compared to fat-soluble substances.)
A little extra B12 is easily flushed out, but when it's a lot, meaning several milligrams per day for many days, it can quickly and suddenly cause very elevated blood pressure and heart rate, e.g. 160 for both SBP and HR. This effect is easy to undo using a good beta blocker, e.g. atenolol, but if one doesn't, then an emergency hospital visit is required. The point is that despite being water soluble, this adverse effect does happen.
Even at just one milligram per day, it can significantly harm sleep.
It has a high circulating half life of six days, which implies that it can really build up if repeatedly megadosed in this period.
I take supplemental B12 and a B-complex because I get hair thinning, brittle nails, and peripheral edema and neuropathy without them. (Also taking levothyroxine and slo iron.) I feel way better with it than without it, and it ain't placebo because I have a terrible habit "memory", forget it often, and remember forgetting after my feet remind me. There's a noticeable point 30 to 90 minutes later at which they spontaneously feel better, but I completely forget about taking or not taking them. (I really need a pill planner like an old person.) I wasn't aware of the apparent connection until after numerous episodes and connecting the two.
The reason I take B12 as a supplement is unrelated to this - I have MTHFR mutation and as such I need to take methyl folate (methylated B9). Apparently this form of B9 absorbs better if it’s combined with the methylated form of B12 (methylcobalamin)
I guess if it will keep my hair color longer that’s a nice side effect!
> Apparently this form of B9 absorbs better if it’s combined with the methylated form of B12 (methylcobalamin)
B9 and B12 are interdependent. When the body uptakes cobalamins, the ligands are pulled off and replaced with ligands sourced from other processes. IIRC in the case of methylcobalamin, the methyl group is pulled off and replaced with a methyl group that’s moved over from methylfolate via a riboflavin-dependent reaction. Been a hot minute since I looked into this so I may have some details incorrect.
It may help, but it will also throw off lab tests while you’re taking it and for a time after. Also, B12 absorption depends strongly on good gut health (ex. no SIBO[1], low gastric acid, pernicious anaemia, etc.), as well as on other medications (ex. metformin[2]) not interfering with absorption.
Most multivitamins are useless because they generally contain suboptimal forms, doses, and ratios. If you want to see good effects, consider individual vitamins in appropriate forms and doses.
The barrier to entry is far too high for most people. A safe, minimal dosage that will help in cases of severe deficiency can be had with an inexpensive pill and negligible time investment.
Regular blood tests and dosing is expensive in mental effort, time, and money.
A regular blood test is mainly needed just for vitamin A, vitamin D, and sometimes for vitamin B6. The rest won't silently cause critical issues if somewhat exceeded.
As for minerals, it is possible to manage the dose without a need for testing.
It’s one of the reasons that regulation would help a lot here. One simple example is chelation. Your body absorbs magnesium when it’s chelated at a rate many multiple times higher than what you might typically get from an OTC multivitamin.
So a multivitamin might contain some magnesium, but what it doesn’t tell you on the label is that the form of magnesium they give you is not going to be absorbed at all and just pass right through your body. Most people need some other formulation of magnesium to actually be absorbed. I would go so far as to say that a fair amount of what goes into a lot of multivitamins on the label is borderline fraud because of stuff like this
Regarding PABA, I have been taking 500 mg/day for years, and it hasn't done anything at all for restoring my hair color or even for freezing further change. A much higher dose of it can be risky and it's not worth the gamble.
I have also been taking B5 as both calcium pantothenate at 500 mg/day and also as pantethine at 300 mg/day for years, neither of which has done anything either in this context.
Similarly, B12 hasn't visibly helped either.
I suspect that copper is the issue with me.
The lowest dose of MitoQ, a 5 mg capsule per day, had lowered my blood pressure significantly after a month of use, well below normal, approaching an unsafe low. Moreover, it took another month after discontinuation of MitoQ for the blood pressure to normalize. I shudder to think how much more powerful SkQ1 would be if taken orally. My first impression is that SkQ1 seems more relevant for local use than for systemic use.
Thanks for your account of these supplements. I thought PABA looked interesting until reading this.
Hopefully some day we can have an over the counter drug that restores or slows graying. I don't have issues with mine beyond it being patchy, distracting.
Just because you are uninformed about certain things doesn't mean everyone else is too. For example, driving on the highway could look dangerous to a person from the jungle, but it isn't to someone who knows what he's doing. Your comment is the same way. If I try or take something, it's because I have studied it reasonably. The things I named are not untested high-risk substances.
In fact, hair colors contain toxic harmful chemicals that even increase the risk of certain cancers. I do color my hair, but I don't like it, and I do it as little as necessary.
Or if you're a male, why bother with coloring at all? Just own the young silver fox look and rock with it. Or shave it and grow a huge beard. As a male you have a lot of natural workarounds against imperfect hair color..
How does that work in the US they pump papers out as evidence of exceptional ability or something along those lines? I thought that mattered for entry visas not for residency.
I had been looking into this recently. My beard is graying and it's annoying me excessively.
10 years ago, the research consensus behind hair graying was, "we don't know what causes it, lol." Today, it's a little bit better understood -- though far from completely understood.
To summarize, there's no known agent that can reliably repigment gray hair. Sometimes powerful drugs repigment hair as a side-effect.
Hair graying results from the dysfunction or loss of melanogenic melanocytes and the depletion or immobility of McSCs, often due to aging or stress.
Lots of cellular signalling pathways are involved. The Wnt/β-Catenin pathway promotes melanocyte stem cell (McSC) proliferation and differentiation, while the MC1R/cAMP pathway, activated by α-MSH, drives melanin production via the MITF transcription factor. The SCF/c-KIT pathway supports melanocyte survival and function, and the Endothelin/EDNRB pathway stimulates both melanocyte proliferation and melanogenesis. In contrast, the PI3K/AKT pathway inhibits melanogenesis by suppressing MITF activity, and the TGF-β pathway maintains McSC quiescence while inhibiting melanogenesis.
Stress is actually a factor because activation of the sympathetic nervous system can deplete McSCs, and neuropeptides like CGRP, SP, and VIP, can either enhance or suppress melanogenesis in ways which are, as yet, unclear. Dermal white adipose tissue (dWAT) near hair follicles also plays a role by secreting factors such as adiponectin that affect hair growth and pigmentation.
A drug to reverse or prevent hair graying would be very welcome, so I hope that the phenomenon becomes better understood in the near future, and then we get products that work.
> My beard is graying and it's annoying me excessively.
So is mine, and now I've lost most of the hair on my head I shave it so completely bald.
But I've learnt to accept it. I don't like it, and wish it was different. There's nothing I can do and I have plenty of more pressing problems to worry about.
So I keep fit and eat reasonably healthily. So even though I look old, I don't have to act it
You've obviously done a bit of research. Have you ever seen the vitamin B12 link referenced in other studies? Are you taking supplements or did you get it tested?
But the B-vitamin in question is calcium pantothenate (B5), and that B5/PABA research is very old -- from the 1940s and 1950s. The results were also hardly anything to write home about; a very mild effect at best.
I don't think that there is a reliable chemical agent to reverse hair graying at the moment, but it seems as though it's become possible in theory to target those mechanisms which appear to be responsible...
Could there be a genetic component to PGH? I started to to get grays at about 14yo so did my sister, and for my mother I only saw her hair color on pictures.
In our world today it seems impossible to complain about stress. Everyone around me from boss to family to even therapist keep telling me to remind myself of how great of a life I have and that I should know better than to complain. But it feels to me like I'm drowning in an ocean stress everyday with no way to escape it. I keep being compared to others who can seemingly take the stress well and am questioned why I can't take similar level of high-stakes, indeterministic responsibilities with severe dangers that are beyond my control, and little to no positive pay-off for me. Some people around me are extremely health conscious, they avoid all kinds of chemicals, eat religiously well, work-out regularly, sleep well etc yet when they show obvious signs of stress because they're working 12 hours a day in their torturous FAANG job, I'm treated like an antivaxxer for pointing it out. In this world of hustle culture, it seems like a taboo to talk about how unhealthy stress is. Stress today is like 70s cigarettes, everybody is doing it, so no need to worry about its health effects.
And yes I have graying hair at mid-late 20s. Sometimes I'm astonished how people don't complain about their stress levels. I feel weak, child-like, immature, and feeble being unable to tolerate maybe 10% of what my wife can.
I drink coffee and tea more for their beneficial phyto chemicals. If I were to stop them, I would lose this benefit. I limit it to a single cup of each.
B6 as P5P at 20 mg twice daily has helped my stress. Similarly, magnesium citrate has too. Theanine is also relevant at night.
I think the best cure for stress for someone who has saved up money is to quit their day job.
Yes, very frustrating. I cannot take stress. It literally makes me psychotic. (I have Schizoaffective Disorder, Bipolar Type) I was making six figures at Cisco in 1999 when I lost it all from the stress.
But now that I have seen my actual genetics, I get it. I am different and there is no adapting for me. My environment needs to look much different or I will die early like my brother and mother. I could work if the job was flexible enough but that is impossible.
Capitalism needs us to be all the same because that is easier to manage. Now that they weeded people like me out they are ramping up the stress and weeding out the more stable people with this BS gig work and hustle meme. You are being crushed for someone elses profit.
P.S. Full head and beard of grey hair at 58 and I love it, would not change it. My grandfather was grey at 50 and lived till he was 98 so who cares.
You can work hard and not be stressed. Stress often comes from lack of control, what are the severe dangers?
The most significant danger seems to be you get a low performance review. As a faang engineer that's a pretty weak a significant danger as there are many other jobs that will simply assume you're good.
Not just lack of control, but lack of a light at the end of the tunnel. A lot of people can tolerate high stress for a while provided they know there's a payoff at the end, an assurance that things are gonna get better.
But when that payoff is taken away or non existent (no money, dead end job, shit living conditions, no chance of home ownership, no having a family, friends group, etc) people can start to fall apart even with low amounts of stress.
Being able to tolerate stress comes down to reasons. If you're doing stuff for good reasons you focus on those and keep your head down. If you don't have good reasons either find some or stop taking on pointless stress.
Slightly off topic, but I have found a Vitamin B supplement all but eliminated my migraines. I was getting them every 1-2 weeks and then, after taking Vitamin B regularly (to counteract alcohol consumption during the festive season), I realised I hadn't had one in ages, despite running on reduced sleep (which seems to be my main trigger).
Anyway, I always make this comment anywhere I can because migraines are horrible, vitamins are cheap and maybe it will help someone else (obviously anecdotal; sample size of 1; I can't find any supporting research etc).
Vitamin B2 (Riboflavin) in particular can be helpful for those with migraines. But it seems like it only effects those with migraines headaches, and not migraine auras. Did nothing for me :-(
Also N=1, but I remember coming across some research that confirmed this when I was taking the supplements.
Conclusions: A pooled analysis of available randomized controlled clinical trials demonstrated that Vitamin B2 400 mg/day for three months supplementation had significant effect on days, duration, frequency, and pain score of migraine attacks.
For some months I've been taking 200 mg/day and it reduced the frequency of my migraine attacks in half.
As someone who started balding at ~19, I would have been very happy with grey hair instead. One person's self-esteem damaging condition is another person's hope.
I would guess you are a man. It's way less bad for us, visibly aging.
One of my oldest friends is a lady who went gray in her 20's. I only found out in her late 30's when she went through some mental health issues and missed aggressively dying to hide the roots.
> In men, graying first occurs in the temples and sideburns. It spreads to the vertex and rest of the scalp involving the occiput the last.
My graying started when I was 15 and first appeared as a single silver strand at the center of my hairline. At 28, I now have a cluster of them in that center spot, as well as diffusely all over my head, including the occiput. I think my temples and sideburns were actually relatively spared.
Also of interest to me: once in a blue moon, I shed a hair that appears to be reverting from gray back to pigmented -- it's gray close to the tip and black closer to the root. I wonder what factors might cause this reversal.
I have no graying of head hair. But I do have several white hairs in my facial hair. I wouldn't have expected to read that "graying first occurs in the temples and sideburns".
(I also have one white hair that grows inside my nose...)
I know this is anecdotal but I know someone that experienced / is experiencing a similar thing. Several silvery hairs reverting back to pigmented after leaving an overly stressful work environment. She only had a few, but of those few perhaps 30%-50% have reverted.
My grandfather started having white hairs at 20, I'm a bit older and I have a few strands of white hair. Honestly, I love white hair. It's not very noticeable on me though, I get it can be embarrassing
This is probably linked to high oxidative stress. H2O2 plays a role both with thyroid production and with greying hair. They talk about it in the paper.
I started going gray at 16. My dad would pull my gray hairs out and marvel at them whenever he saw one - without thinking to ask first, of course. they joked it must be from stress - disquieting that it might have been metabolic, and that they never considered taking me to a doctor.
I started graying in my mid twenties, I am in my late thirties now and my hair is a little over half gray at this point. I would frankly like to do something about it, my wife has been insistent that I don't because she likes it.
The possibility of it being some sort of vitamin deficiency that this raises has me feeling like I should at least get my levels tested. I can't imagine that it is a B12 deficiency however due to how much canned fish I consume. It's become my go to easy lunch since the beginning of COVID.
> I started graying in my mid twenties, I am in my late thirties now and my hair is a little over half gray at this point. I would frankly like to do something about it, my wife has been insistent that I don't because she likes it.
Full grey here. The amount of comments and compliments I get about my hair is unreal. I never really got any before greying.
Be careful with the canned fish, especially canned sardines, as they risk arsenic. Canned tuna and some others can risk mercury. I wouldn't eat canned fish more than once or twice a week. Always make sure to cook them well, otherwise worms are risked. The ocean is used by us as one big garbage dump.
You shouldn't have to, but you would be taking a massive risk, and risk becoming a medical statistic when worms grow and multiply, also entering various organs.
In me, canned tuna caused major problems that required antibiotics to resolve after conducting thousands of dollars of tests. The tuna evidently had certain highly inflammatory bacteria. I consider myself lucky that the antibiotic worked at all.
> Vitamin B12 deficiency can cause PGH through unknown mechanism. About 55% of patients with pernicious anemia had graying before 50 years as compared to 30% in the control group.[32]
/soapbox
Get your B12 tested (before taking supplements!).
B12 deficiency is known to present in many ways, and also to be often overlooked in clinical settings[1]. It’s known that not everyone presents with the anaemia from it[2], which is often why it’s skipped as a diagnostic option. Additionally, long-term/severe deficiency can present with symptoms almost identical to multiple sclerosis[3]. Deficiency of other B vitamins, such as B2, can cause a functional B12 deficiency as well[4]. It’s also known that supplementation will falsely elevate levels even in the presence of a deficiency.
/unsoapbox
[1] https://www.mcpiqojournal.org/article/S2542-4548(19)30033-5/...
[2] https://www.bmj.com/content/383/bmj-2022-071725
[3] https://researchonline.nd.edu.au/cgi/viewcontent.cgi?article...
[4] https://www.iomcworld.org/articles/paradoxical-vitamin-b12-d...
The paradoxical B12 deficiency might have a relation with the inactive form being supplemented. If one supplements cyanocobalamin, and one expects the body to convert it to methylcobalamin, and if this conversion doesn't happen for whatever reason, and if the measured form includes the inactive form, then "paradoxical B12 deficiency" can be observed.
There is a more insidious form of it whereby the active form doesn't enter the brain. Symptoms are: difficulty speaking, tremors and ataxia. This can be tested by CSF (cerebrospinal fluid) testing. This assumes that the active form is supplemented and it is present in blood. It can be remedied by a course of corticosteroid pills, followed by megadosing B12 orally daily. Refer to PMID 38924428.
I take a triple active form of it which is methyl+hydroxy+adenosyl, covering all bases, but a total of just 500 mcg per day, above which it harms my sleep.
Would you mind sharing a brand or a link? I have had grey hair since I was in my 20s and struggle with energy. I have been taking nature made multi vitamin for a vitamin b deficiency that was high enough to cause craggy edges on my tongue, caused by the stomach acid suppressant I was prescribed. I would like to compare.
https://www.amazon.com/gp/aw/d/B09G6ZDCDP
Use it with a 2-way or 3-way pill splitter, just once piece per day.
For acid, use famotidine to the extent possible, in as low a dose as does the job. For overnight suppression, however, omeprazole is useful.
Thanks!
> The paradoxical B12 deficiency might have a relation with the inactive form being supplemented.
Yup, not everyone can convert cyanocobalamin or hydroxocobalamin to adenosyl-/methylcobalamin. Especially in severe cases, anecdotally I’ve seen people not make progress with the standard cyanocobalamin injections, but then make huge progress with methylcobalamin injections. Unfortunately, methylcobalamin is often not preferred in injectable form due to very quick degradation into hydroxocobalamin upon exposure to light.
Taking methylcobalamin B12 supplements essentially fixed my memory problems. Early on I tried out the cyanocobalamin type and got absolutely nothing from it.
If I stop taking the supplements for a few weeks, the memory problems come back. If I start again, a week later my memory is excellent. It’s well worth the minor effort.
What kind of memory problems, could you expand? I wonder if I fall on this bucket. I had graying hairs as soon as I finished high school (~19). One of my major problems with studying was an inability to retain stuff in university, which is weird because through middle school a single read was sufficient for me to retain stuff.
Mostly noun recall. I can mentally picture and describe thing or person X, but when I'm having the problem it could possibly take me 30 minutes to figure out the name of X without looking it up.
Subligual methylcobalamin works just as well as the shots and you can buy it anywhere.
Also, get a Methylmalonic Acid Test with you B12 levels. An MMA test is more useful because it is an enz=yme which uses B12, so when the active form of B12 is low, so will MMA in most cases.
> Subligual methylcobalamin works just as well as the shots
It does not. The cobalamin molecules are quite large and don’t penetrate the sublingual mucosa very well. On top of that, the proteins in saliva that bind to B12s will cause any bound B12 to not absorb sublingually, instead having to wait to make it through the digestive system for intestinal uptake.
Sublingual is still certainly a better option than oral pills, but the injections are preferable in severe cases for a reason.
> The cobalamin molecules are quite large and don’t penetrate the sublingual mucosa very well.
Absolute nonsense.
Did you even bother to look for one paper on the subject? Here are a few:
https://www.scielo.org.mx/scielo.php?pid=S0034-8376202000060...
https://pubmed.ncbi.nlm.nih.gov/34871525/
https://www.proquest.com/openview/e9a25963dbc92150e420a3a847...
Ok, so assuming you don’t want to have your CSF tested, is there any risk of harm to supplementing with the active form?
There's no risk in non-smokers if you stick to a sane dose. Megadosing it can harm sleep and severely increase blood pressure and heart rate, although these gradually reverse upon cessation. This can take time to manifest. It is why I limit the dose to 500 mcg per day. Older people, such as those over 70, can need more and tolerate more, even 5 mg per day, due to deteriorated absorption.
Also, don't forget the other B vitamins. In truth I take them all.
> Megadosing it can harm sleep and severely increase blood pressure and heart rate
https://www.researchgate.net/profile/Osama-Arafat/publicatio...
> METHYLCOBALAMIN HAS AN EFFECT ON HYPOTHALAMIC–HYPOPHYSEAL– ADRENAL AXIS
In rats, but may apply to humans too.
> There's no risk in non-smokers if you stick to a sane dose.
Also, B12 is water soluble, which generally means that your body is pretty good at flushing out any excess it can't use, making it difficult to overdose on. (Compared to fat-soluble substances.)
A little extra B12 is easily flushed out, but when it's a lot, meaning several milligrams per day for many days, it can quickly and suddenly cause very elevated blood pressure and heart rate, e.g. 160 for both SBP and HR. This effect is easy to undo using a good beta blocker, e.g. atenolol, but if one doesn't, then an emergency hospital visit is required. The point is that despite being water soluble, this adverse effect does happen.
Even at just one milligram per day, it can significantly harm sleep.
It has a high circulating half life of six days, which implies that it can really build up if repeatedly megadosed in this period.
Does it help you with grey hair ?
No, it's useless to me in this regard, although it could help someone who is efficient. I think my issue may have more to do with copper.
I take supplemental B12 and a B-complex because I get hair thinning, brittle nails, and peripheral edema and neuropathy without them. (Also taking levothyroxine and slo iron.) I feel way better with it than without it, and it ain't placebo because I have a terrible habit "memory", forget it often, and remember forgetting after my feet remind me. There's a noticeable point 30 to 90 minutes later at which they spontaneously feel better, but I completely forget about taking or not taking them. (I really need a pill planner like an old person.) I wasn't aware of the apparent connection until after numerous episodes and connecting the two.
Use a pill box. It's not just for old people. It's good for everyone.
Interesting. I had it 5 years ago and then it went away. It started again a few weeks ago and I halved my vitamin B supplementing a while before that.
The reason I take B12 as a supplement is unrelated to this - I have MTHFR mutation and as such I need to take methyl folate (methylated B9). Apparently this form of B9 absorbs better if it’s combined with the methylated form of B12 (methylcobalamin)
I guess if it will keep my hair color longer that’s a nice side effect!
> Apparently this form of B9 absorbs better if it’s combined with the methylated form of B12 (methylcobalamin)
B9 and B12 are interdependent. When the body uptakes cobalamins, the ligands are pulled off and replaced with ligands sourced from other processes. IIRC in the case of methylcobalamin, the methyl group is pulled off and replaced with a methyl group that’s moved over from methylfolate via a riboflavin-dependent reaction. Been a hot minute since I looked into this so I may have some details incorrect.
Also, over half the world's population has H. Pylori, which interferes with B12 absorption.
It’s also known that supplementation will falsely elevate levels even in the presence of a deficiency.
It sounds to me that what you’re saying is that a daily multivitamin would not help in this case.
It may help, but it will also throw off lab tests while you’re taking it and for a time after. Also, B12 absorption depends strongly on good gut health (ex. no SIBO[1], low gastric acid, pernicious anaemia, etc.), as well as on other medications (ex. metformin[2]) not interfering with absorption.
[1] https://en.wikipedia.org/wiki/Small_intestinal_bacterial_ove...
[2] https://en.wikipedia.org/wiki/Metformin CTRL-F "B12"
Genetics will play a huge role in B12 absorption. Transcobalamin to be specific.
https://ashpublications.org/blood/article/114/22/1989/111148...
Most multivitamins are useless because they generally contain suboptimal forms, doses, and ratios. If you want to see good effects, consider individual vitamins in appropriate forms and doses.
The barrier to entry is far too high for most people. A safe, minimal dosage that will help in cases of severe deficiency can be had with an inexpensive pill and negligible time investment.
Regular blood tests and dosing is expensive in mental effort, time, and money.
A regular blood test is mainly needed just for vitamin A, vitamin D, and sometimes for vitamin B6. The rest won't silently cause critical issues if somewhat exceeded.
As for minerals, it is possible to manage the dose without a need for testing.
Thank you. I will go get those tests.
It’s one of the reasons that regulation would help a lot here. One simple example is chelation. Your body absorbs magnesium when it’s chelated at a rate many multiple times higher than what you might typically get from an OTC multivitamin.
So a multivitamin might contain some magnesium, but what it doesn’t tell you on the label is that the form of magnesium they give you is not going to be absorbed at all and just pass right through your body. Most people need some other formulation of magnesium to actually be absorbed. I would go so far as to say that a fair amount of what goes into a lot of multivitamins on the label is borderline fraud because of stuff like this
Regarding PABA, I have been taking 500 mg/day for years, and it hasn't done anything at all for restoring my hair color or even for freezing further change. A much higher dose of it can be risky and it's not worth the gamble.
I have also been taking B5 as both calcium pantothenate at 500 mg/day and also as pantethine at 300 mg/day for years, neither of which has done anything either in this context.
Similarly, B12 hasn't visibly helped either.
I suspect that copper is the issue with me.
The lowest dose of MitoQ, a 5 mg capsule per day, had lowered my blood pressure significantly after a month of use, well below normal, approaching an unsafe low. Moreover, it took another month after discontinuation of MitoQ for the blood pressure to normalize. I shudder to think how much more powerful SkQ1 would be if taken orally. My first impression is that SkQ1 seems more relevant for local use than for systemic use.
> I suspect that copper is the issue with me.
Prolonged copper deficiency can cause irreversible neuropathies and CNS damage. You should try to get tested for it if you can.
Thanks for your account of these supplements. I thought PABA looked interesting until reading this.
Hopefully some day we can have an over the counter drug that restores or slows graying. I don't have issues with mine beyond it being patchy, distracting.
seems like unnecessary dangerous experimentation with the hopes of something cosmetic. why not just color hair?
Just because you are uninformed about certain things doesn't mean everyone else is too. For example, driving on the highway could look dangerous to a person from the jungle, but it isn't to someone who knows what he's doing. Your comment is the same way. If I try or take something, it's because I have studied it reasonably. The things I named are not untested high-risk substances.
In fact, hair colors contain toxic harmful chemicals that even increase the risk of certain cancers. I do color my hair, but I don't like it, and I do it as little as necessary.
The highway is remarkably dangerous for even excellent drivers
Dangerous compared to what?
Because in terms of driving highways are safer (have less accidents) than urban and rural roads, and the most dangerous areas are intersections.
You are absolutely correct, of course, but that's clearly not the context I used it in.
If the gray hair indicates an underlying health issue/deficiency, dying them is not going to help with that.
>why not just color hair?
Or if you're a male, why bother with coloring at all? Just own the young silver fox look and rock with it. Or shave it and grow a huge beard. As a male you have a lot of natural workarounds against imperfect hair color..
Some of us don't grow beards, so you just end up looking like a tall child struggling on hard times.
> INTRODUCTION Haalthy hair is a sign of general well-being and youth.
Not exactly confidence inspiring when the very first word is a typo.
I looked at INTRODUCTION letter-by-letter several times before realizing the spelling issue is in “Haalthy”. That’s the second word.
Headings don’t count as the body text
Author list, author affiliation and past history all suggest this might be a green card paper.
How does that work in the US they pump papers out as evidence of exceptional ability or something along those lines? I thought that mattered for entry visas not for residency.
+1 how is this even possible to do?
I had been looking into this recently. My beard is graying and it's annoying me excessively.
10 years ago, the research consensus behind hair graying was, "we don't know what causes it, lol." Today, it's a little bit better understood -- though far from completely understood.
There's a handy review article here: https://pmc.ncbi.nlm.nih.gov/articles/PMC10535703/
To summarize, there's no known agent that can reliably repigment gray hair. Sometimes powerful drugs repigment hair as a side-effect.
Hair graying results from the dysfunction or loss of melanogenic melanocytes and the depletion or immobility of McSCs, often due to aging or stress.
Lots of cellular signalling pathways are involved. The Wnt/β-Catenin pathway promotes melanocyte stem cell (McSC) proliferation and differentiation, while the MC1R/cAMP pathway, activated by α-MSH, drives melanin production via the MITF transcription factor. The SCF/c-KIT pathway supports melanocyte survival and function, and the Endothelin/EDNRB pathway stimulates both melanocyte proliferation and melanogenesis. In contrast, the PI3K/AKT pathway inhibits melanogenesis by suppressing MITF activity, and the TGF-β pathway maintains McSC quiescence while inhibiting melanogenesis.
Stress is actually a factor because activation of the sympathetic nervous system can deplete McSCs, and neuropeptides like CGRP, SP, and VIP, can either enhance or suppress melanogenesis in ways which are, as yet, unclear. Dermal white adipose tissue (dWAT) near hair follicles also plays a role by secreting factors such as adiponectin that affect hair growth and pigmentation.
A drug to reverse or prevent hair graying would be very welcome, so I hope that the phenomenon becomes better understood in the near future, and then we get products that work.
> My beard is graying and it's annoying me excessively.
So is mine, and now I've lost most of the hair on my head I shave it so completely bald.
But I've learnt to accept it. I don't like it, and wish it was different. There's nothing I can do and I have plenty of more pressing problems to worry about.
So I keep fit and eat reasonably healthily. So even though I look old, I don't have to act it
I've also learnt to accept my recewding and thinning hairs.
Yet, Everytime I look in the mirror I also don't like it and wish it were different.
Have I really accepted it?
No but beating yourself up over whether or not you've accepted it won't help.
You've obviously done a bit of research. Have you ever seen the vitamin B12 link referenced in other studies? Are you taking supplements or did you get it tested?
As far as hair graying is concerned, I don't think that B12 does much unless you're seriously deficient in it.
There's some research in B-vitamins and PABA for hair repigmentation, reviewed (among other things) here: https://pmc.ncbi.nlm.nih.gov/articles/PMC6995950/
But the B-vitamin in question is calcium pantothenate (B5), and that B5/PABA research is very old -- from the 1940s and 1950s. The results were also hardly anything to write home about; a very mild effect at best.
I don't think that there is a reliable chemical agent to reverse hair graying at the moment, but it seems as though it's become possible in theory to target those mechanisms which appear to be responsible...
Could there be a genetic component to PGH? I started to to get grays at about 14yo so did my sister, and for my mother I only saw her hair color on pictures.
In our world today it seems impossible to complain about stress. Everyone around me from boss to family to even therapist keep telling me to remind myself of how great of a life I have and that I should know better than to complain. But it feels to me like I'm drowning in an ocean stress everyday with no way to escape it. I keep being compared to others who can seemingly take the stress well and am questioned why I can't take similar level of high-stakes, indeterministic responsibilities with severe dangers that are beyond my control, and little to no positive pay-off for me. Some people around me are extremely health conscious, they avoid all kinds of chemicals, eat religiously well, work-out regularly, sleep well etc yet when they show obvious signs of stress because they're working 12 hours a day in their torturous FAANG job, I'm treated like an antivaxxer for pointing it out. In this world of hustle culture, it seems like a taboo to talk about how unhealthy stress is. Stress today is like 70s cigarettes, everybody is doing it, so no need to worry about its health effects.
And yes I have graying hair at mid-late 20s. Sometimes I'm astonished how people don't complain about their stress levels. I feel weak, child-like, immature, and feeble being unable to tolerate maybe 10% of what my wife can.
Unsolicited advice : have you tried stopping coffee / caffeine? This improved my stress levels immensely although I only drank one cup a day.
I drink coffee and tea more for their beneficial phyto chemicals. If I were to stop them, I would lose this benefit. I limit it to a single cup of each.
B6 as P5P at 20 mg twice daily has helped my stress. Similarly, magnesium citrate has too. Theanine is also relevant at night.
I think the best cure for stress for someone who has saved up money is to quit their day job.
+1
Yes, very frustrating. I cannot take stress. It literally makes me psychotic. (I have Schizoaffective Disorder, Bipolar Type) I was making six figures at Cisco in 1999 when I lost it all from the stress.
But now that I have seen my actual genetics, I get it. I am different and there is no adapting for me. My environment needs to look much different or I will die early like my brother and mother. I could work if the job was flexible enough but that is impossible.
Capitalism needs us to be all the same because that is easier to manage. Now that they weeded people like me out they are ramping up the stress and weeding out the more stable people with this BS gig work and hustle meme. You are being crushed for someone elses profit.
P.S. Full head and beard of grey hair at 58 and I love it, would not change it. My grandfather was grey at 50 and lived till he was 98 so who cares.
You can work hard and not be stressed. Stress often comes from lack of control, what are the severe dangers?
The most significant danger seems to be you get a low performance review. As a faang engineer that's a pretty weak a significant danger as there are many other jobs that will simply assume you're good.
>Stress often comes from lack of control
Not just lack of control, but lack of a light at the end of the tunnel. A lot of people can tolerate high stress for a while provided they know there's a payoff at the end, an assurance that things are gonna get better.
But when that payoff is taken away or non existent (no money, dead end job, shit living conditions, no chance of home ownership, no having a family, friends group, etc) people can start to fall apart even with low amounts of stress.
Being able to tolerate stress comes down to reasons. If you're doing stuff for good reasons you focus on those and keep your head down. If you don't have good reasons either find some or stop taking on pointless stress.
Slightly off topic, but I have found a Vitamin B supplement all but eliminated my migraines. I was getting them every 1-2 weeks and then, after taking Vitamin B regularly (to counteract alcohol consumption during the festive season), I realised I hadn't had one in ages, despite running on reduced sleep (which seems to be my main trigger).
Anyway, I always make this comment anywhere I can because migraines are horrible, vitamins are cheap and maybe it will help someone else (obviously anecdotal; sample size of 1; I can't find any supporting research etc).
Vitamin B2 (Riboflavin) in particular can be helpful for those with migraines. But it seems like it only effects those with migraines headaches, and not migraine auras. Did nothing for me :-(
Also N=1, but I remember coming across some research that confirmed this when I was taking the supplements.
Interesting. I still often feel like I am about to get a migraine (colours go weird, slight auras, blurry vision), but they don't eventuate.
There are studies that support this: https://pubmed.ncbi.nlm.nih.gov/33779525/
Conclusions: A pooled analysis of available randomized controlled clinical trials demonstrated that Vitamin B2 400 mg/day for three months supplementation had significant effect on days, duration, frequency, and pain score of migraine attacks.
For some months I've been taking 200 mg/day and it reduced the frequency of my migraine attacks in half.
Thanks for posting this - just what I was after.
Which B vitamin(s)? there are a number of them.
Looks like B2 is the one that helps
As someone who started balding at ~19, I would have been very happy with grey hair instead. One person's self-esteem damaging condition is another person's hope.
As someone who got grey hair in their 20's and doesn't have to deal with it thinning, I am aware of my good fortune.
Man I sure know a lot of early 30 year olds with graying hair
Well I have gray hair since I was 16. It never made me feel insecure.
I would guess you are a man. It's way less bad for us, visibly aging.
One of my oldest friends is a lady who went gray in her 20's. I only found out in her late 30's when she went through some mental health issues and missed aggressively dying to hide the roots.
Leaving aside other health concerns grey hair can be attractive on all genders and should be respected and celebrated.
> In men, graying first occurs in the temples and sideburns. It spreads to the vertex and rest of the scalp involving the occiput the last.
My graying started when I was 15 and first appeared as a single silver strand at the center of my hairline. At 28, I now have a cluster of them in that center spot, as well as diffusely all over my head, including the occiput. I think my temples and sideburns were actually relatively spared.
Also of interest to me: once in a blue moon, I shed a hair that appears to be reverting from gray back to pigmented -- it's gray close to the tip and black closer to the root. I wonder what factors might cause this reversal.
I have no graying of head hair. But I do have several white hairs in my facial hair. I wouldn't have expected to read that "graying first occurs in the temples and sideburns".
(I also have one white hair that grows inside my nose...)
> I wonder what factors might cause this reversal.
Very likely: Stress. Also diet and exercise. They are interrelated. But for people that I’ve known have hair go gray and back again, it was stress.
I know this is anecdotal but I know someone that experienced / is experiencing a similar thing. Several silvery hairs reverting back to pigmented after leaving an overly stressful work environment. She only had a few, but of those few perhaps 30%-50% have reverted.
There seems to be a lot about immune system activation attacking melanocytes like this:
https://www.uab.edu/news/research/item/9390-study-explains-o....
Thus not surprisingly “Covid and gray hair” brings some results too, including reversing of Covid associated gray hair.
My grandfather started having white hairs at 20, I'm a bit older and I have a few strands of white hair. Honestly, I love white hair. It's not very noticeable on me though, I get it can be embarrassing
I started graying when I fucked around with nicotine for a bit.
It can also be caused by autoimmune thyroidism
But what causes autoimmune hypothyroidism? (Hint, it is probably oxidative stress.)
Receipts:
https://pmc.ncbi.nlm.nih.gov/articles/PMC5040049/
https://www.sciencedirect.com/science/article/abs/pii/S00088...
https://link.springer.com/article/10.1186/s12902-023-01348-9
https://etj.bioscientifica.com/view/journals/etj/12/6/ETJ-23...
I was diagnosed with hypothyroidism a decade ago and it seems to coincide with premature graying in my 30s
This is probably linked to high oxidative stress. H2O2 plays a role both with thyroid production and with greying hair. They talk about it in the paper.
I started going gray at 16. My dad would pull my gray hairs out and marvel at them whenever he saw one - without thinking to ask first, of course. they joked it must be from stress - disquieting that it might have been metabolic, and that they never considered taking me to a doctor.
So what's the best brand for coloring grey hair. Preferably non toxic.
I use this.
https://www.amazon.com/American-Crew-Precision-Blend-Hair/dp...
It’s a temporary hair color, which tends not to damage your hair. I find it lasts about a month.
Henna? Though it will give your hair a shade of red and not black.
I started graying in my mid twenties, I am in my late thirties now and my hair is a little over half gray at this point. I would frankly like to do something about it, my wife has been insistent that I don't because she likes it.
The possibility of it being some sort of vitamin deficiency that this raises has me feeling like I should at least get my levels tested. I can't imagine that it is a B12 deficiency however due to how much canned fish I consume. It's become my go to easy lunch since the beginning of COVID.
> I started graying in my mid twenties, I am in my late thirties now and my hair is a little over half gray at this point. I would frankly like to do something about it, my wife has been insistent that I don't because she likes it.
Full grey here. The amount of comments and compliments I get about my hair is unreal. I never really got any before greying.
I say embrace it.
Be careful with the canned fish, especially canned sardines, as they risk arsenic. Canned tuna and some others can risk mercury. I wouldn't eat canned fish more than once or twice a week. Always make sure to cook them well, otherwise worms are risked. The ocean is used by us as one big garbage dump.
You shouldn't need to cook canned fish, they are cooked after canning at the factory, which is why they are shelf stable for years.
You shouldn't have to, but you would be taking a massive risk, and risk becoming a medical statistic when worms grow and multiply, also entering various organs.
In me, canned tuna caused major problems that required antibiotics to resolve after conducting thousands of dollars of tests. The tuna evidently had certain highly inflammatory bacteria. I consider myself lucky that the antibiotic worked at all.
This title had me hoping that this was a gwern article
TLDR: root cause is working with dynamic and weakly typed languages and poorly documented and maintained spaghetti code
tldr: stress
lol at scientific papers using the word "caucasian" like it's the 70s
OT, but I can't not notice the wild domain.