> 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.
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.
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.
Readit News
/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...
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.
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.
I guess if it will keep my hair color longer that’s a nice side effect!
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 sounds to me that what you’re saying is that a daily multivitamin would not help in this case.
[1] https://en.wikipedia.org/wiki/Small_intestinal_bacterial_ove...
[2] https://en.wikipedia.org/wiki/Metformin CTRL-F "B12"
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.
Prolonged copper deficiency can cause irreversible neuropathies and CNS damage. You should try to get tested for it if you can.
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.
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..
Not exactly confidence inspiring when the very first word is a typo.
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.
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
Yet, Everytime I look in the mirror I also don't like it and wish it were different.
Have I really accepted 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...
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.
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.
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.
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.
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).
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.