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What can we learn from B6 toxicity recovery?
I notice some unexpected similarities between Vitamin B6 and Vitamin A toxicity.
First of all, the paradoxical connection between deficiency and toxicity:
- B6 can be used to treat neuropathy[3], skin rash[1], depression[1], anxiety[1], eye problems[6], headache[7]
- ...But B6 toxicity may cause neuropathy[4], skin rash[2], depression[5], anxiety[2][5], eye problems[2][5], headache[2][5]
- B6 deficiency is linked to temperature regulation problems[8], hip fractures[9], lung cancer[18]
- ...But B6 toxicity is also linked to temperature regulation problems[2], hip fractures[10], lung cancer[11]
- "Ironically, Vitamin B6 deficiency, which is very rare, mirrors many of the symptoms of Vitamin B6 Toxicity."[5]
Even if you suspect you have B6 toxicity, official sources make it sound unlikely, for similar reasons that Vitamin A toxicity will sound unlikely:
- B6 blood test will likely look normal (unless caught in the first 2-4 weeks)[2][5]
- Just as beta carotene is "water soluble" so it supposedly does "not accumulate in the body" [19], B6 is also "water soluble" and supposedly "unused amounts will exit the body through the urine"[20]. But like A, B6 is stored in ester form[17][14].
- B6 toxicity is well known, but it's supposed to only happen at 1000mg/day[4]. The upper limit is 100mg/day[4]. But patients report symptoms from as little as 1mg/day[5]
- Just as A toxicity supposedly never happens from the beta carotene form, information about B6 toxicity focuses on pyridoxine form[4] and if you have trouble "converting" that form, another form (P5P) is often recommended.[15] However, "Toxicity may be due to the pyridoxine base or one of the metabolites."[17]
The process of recovery from B6 toxicity sounds similar to Vitamin A recovery:
- B6 is in most food, but white rice and white bread are known as safe[2]
- During recovery, symptoms can quickly return with very low dose in food -- a possible autoimmune reaction?[5]
- Low B6 diet helps within months, but patients report re-worsening of symptoms at six months[2]
- Recovery takes months, maybe years[5], and damage can be irreversible
- Like A toxicity, B6 toxicity can cause skin sores[21], sunlight sensitivity[16], blurry vision[2][5], dizziness[2][5], lack of coordination[16]
- Like A toxicity, B6 toxicity is known to cause painful burning sensations[2][5][23][24]
- Exercise and hot baths recommended, although they can temporarily worsen symptoms[2][5]
- Supplement manufacturers acknowledge that some patients don't want B6 in a multivitamin[12][13] (similar to how a multivitamin without A and D is available[22])
- Long-term, staying under the RDA might be safe: Coburn et al write "...B-6 has never been associated with widespread naturally occurring deficiency disorders comparable with scurvy and beriberi nor has any unique health problem been identified in 80% of the female population whose average vitamin B-6 intake is substantially less than the RDA." and they suggest a daily requirement of more like 0.25 to 0.5mg (the official RDA is around 1 to 2mg).[17]
Even B6's chemistry sounds similar to Vitamin A's:
- Has an alcohol form (pyridoxine)[15]
- Has an aldehyde form (pyridoxal)[15]
- Has an ester form (P5P)[15][14] used for body stores[17]
Sources:
- https://ods.od.nih.gov/factsheets/VitaminB6-Consumer/
- https://www.facebook.com/groups/646501652136321/announcements/ (requires joining)
- https://www.healthline.com/nutrition/vitamin-b6-deficiency-symptoms
- https://lpi.oregonstate.edu/mic/vitamins/vitamin-B6
- https://www.facebook.com/groups/956840724404017/permalink/2341600509261358/ (requires joining)
- https://www.healthline.com/nutrition/vitamin-b6-benefits#section8
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4919187/
- https://www.ncbi.nlm.nih.gov/pubmed/5877413
- https://www.ncbi.nlm.nih.gov/pubmed/1471512
- https://medicalxpress.com/news/2019-10-vitamin-hip-fracture.html
- https://www.health.harvard.edu/cancer/b-vitamins-may-raise-risk-of-lung-cancer-in-men-who-smoke
- https://www.desertharvest.com/b-complex-without-b6-90-capsules.html
- https://www.virtuoos.com/en/product/multi-health-support-gold-2/
- https://www.wikidata.org/wiki/Q418957
- https://selfhacked.com/blog/vitamin-b6/
- https://www.mayoclinic.org/drugs-supplements-vitamin-b6/art-20363468
- https://www.ncbi.nlm.nih.gov/pubmed/2035470
- https://www.ncbi.nlm.nih.gov/pubmed/29238985
- https://www.drweil.com/vitamins-supplements-herbs/vitamins/how-much-vitamin-a-is-safe/
- https://www.hsph.harvard.edu/nutritionsource/vitamin-b6/
- https://www.winchesterhospital.org/health-library/article?id=14068
- https://www.amazon.com/Kirkman-Labs-EveryDay-Multi-Vitamin-Vitamins/dp/B00P8DX0DS
- https://academic.oup.com/painmedicine/article/18/8/1593/3089770
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4199287/
I'm not ready to draw conclusions but when I took a p5p supplement 5 years ago it made my insomnia worse immediately, and went away immediately after stopping. Retinol supplements took much longer to make my insomnia worse but I was also taking supplements that might have blunted the effects somewhat from "vitamin" A in the short term. The effects of "vitamin" A have been very long lasting and maybe permanent I fear for me.
Liver is bad. It tastes disgusting. Don't consume it. Other than liver, I don't think I'd worry about foods containing B6, unless of course it has a lot of retinol too and one is on a retinoid detox diet.
I first read about B6 toxicity a few years ago but I didn't know all this, very interesting, thanks for posting.
Especially this: "...B-6 has never been associated with widespread naturally occurring deficiency disorders comparable with scurvy and beriberi nor has any unique health problem been identified in 80% of the female population whose average vitamin B-6 intake is substantially less than the RDA."
But the problem is, the people often take supraphysiological doses of vitamins... B6 is everywhere, in magnesium supplements, in energy drinks, every b complex has doses 50-100 mg of B6. People buy B6 supplement and they think, this dose is "normal" because they can buy it: https://www.iherb.com/pr/Natural-Factors-Vitamin-B6-Pyridoxine-HCl-100-mg-90-Tablets/2530
But how much of B6 is in food sources?:
http://www.whfoods.com/genpage.php?tname=nutrient&dbid=108 - you can take max. 3-4 mg of B6 daily in foods! But you can buy everywhere 100 mg dose - these supplements need maybe people with metabolic disordes as pyrroluria.
or DHEA hormone... this dose can be totall toxic for most people:
https://www.iherb.com/pr/Life-Extension-DHEA-100-mg-60-Vegetarian-Capsules/47822
People do not realize that what doses of B vitamins are in real foods and what they take in supplements.
Biotin in foods, you can take maximal dose in foods up to 30 mcg daily but you can buy the dose 5000 mcg:
https://www.iherb.com/pr/Now-Foods-Biotin-5-000-mcg-120-Veg-Capsules/3319
And this is with every possible vitamin, mineral, B1, B2, B5, B12, PABA, vitamin E, vitamin K- especially MK-7 form, zinc...
And then people are sick from supplements, they take high doses of biotin for hair but too much biotin causes B5 deficiency:
https://hbfit.com/does-biotin-cause-acne/
"Vitamin B7 is absorbed through receptors in the intestines, and so is vitamin B5. Because they are both absorbed through the same receptors, if there is an excess of one, there is a deficiency in another."
Or they take isolated zinc and became deficient in copper but in foods is always zinc and copper together but in various ratio. The same with magnesium, calcium, phosphorus. People take high doses of magnesium and become deficient in calcium... But every food has magnesium, calcium, phosphorus, only in various ratio. Taking isolated vitamins, minerals in high doses is always risky.
B6 in energy drinks:
https://superhumanradio.net/blog/is-your-energy-drink-causing-mysterious-neurological
Hi @dan It’s all very interesting (as I’ve said before on FB). Great post. Just one point - beta carotene I’m pretty sure is fat soluble. If absorbed but not converted to x2 retinaldehydes, it is transported in chylomicrons & stored in fat. BCO1 knockout mice (they cannot convert betacarotene to retinaldehyde) accumulate lots of orange fat 🐭
I’m intrigued by B6 toxicity & rather shocked as I was supplementing with quite high doses for pyroluria at one time. I thought it made me feel better but it could have been the zinc or something else (I certainly need zinc). I didn’t seem to get any negative effects such as tingling in limbs & it’s quite shocking that these poor people are having such a terrible time from quite small amounts of B6. I think that vitamin A toxicity has been a problem for me for many years getting consistently worse so I don’t think that vA toxicity can make you more vulnerable to B6 - maybe the opposite if I’m anything to go by!
Thank you so much Dan for bringing this information to my notice. I’m sure there is some connection to vA toxicity but I don’t know what. I’m not going to be supplementing any B6 again.
Jenny
This is disturbing to me too, but it has disturbed me for quite awhile - it's not your fault. 🙂 I have been supplementing my son, my daughter, and myself for years now, with B6/zinc for low-grade pyroluria. It DEFINITELY makes a difference, but I hope to wean off the supps soon, with the idea that perhaps the A toxicity was causing us to need so much of the B/zinc combo in the first place. It's crazy to take such high doses as we take, even when Mensah doctors convinced me that our blood tests showed the need (it was the resolution/management of symptoms that convinced me, though).
But when I tried to lower our doses last month, my son's mood was getting lower and my daughter's headaches started up again. Not sure if this could be due to a "rebound" effect, or whether we still need a lot of these things. ...
The symptoms of VAD are completely different from those of Hypervitaminosis A, some myths refuse to die. The only proven symptom of VAD is xerophthalmia.
The reason B6 toxicity symptoms are the same as deficiency symptoms is because toxicity is deficiency. Pyridoxine competitively inhibits P5P so a large amount of pyridoxine creates a deficiency. Some people have problems converting pyridoxine to P5P in the first place, these people are the likely ones that react negatively to small amounts of pyridoxine. These people have low pyridoxal kinase activity. Holistically restoring health to improve enzyme function is the correct approach, not life long supplementation with P5P.
Never take anything that contains a lot of pyridoxine. As an example Berocca contains 10 mg of pyridoxine, I doubt this is problematic for most people. I wouldn't go much higher than that though. If you take P5P you shouldn't have a problem however I would caution against taking any supplement over an extended period that provides any nutrient far in excess of what we would normally get in food.
The vitamin B6 paradox: Supplementation with high concentrations of pyridoxine leads to decreased vitamin B6 function.
Abstract
Vitamin B6 is a water-soluble vitamin that functions as a coenzyme in many reactions involved in amino acid, carbohydrates and lipid metabolism. Since 2014, >50 cases of sensory neuronal pain due to vitamin B6 supplementation were reported. Up to now, the mechanism of this toxicity is enigmatic and the contribution of the various B6 vitamers to this toxicity is largely unknown. In the present study, the neurotoxicity of the different forms of vitamin B6 is tested on SHSY5Y and CaCo-2 cells. Cells were exposed to pyridoxine, pyridoxamine, pyridoxal, pyridoxal-5-phosphate or pyridoxamine-5-phosphate for 24h, after which cell viability was measured using the MTT assay. The expression of Bax and caspase-8 was tested after the 24h exposure. The effect of the vitamers on two pyridoxal-5-phosphate dependent enzymes was also tested. Pyridoxine induced cell death in a concentration-dependent way in SHSY5Y cells. The other vitamers did not affect cell viability. Pyridoxine significantly increased the expression of Bax and caspase-8. Moreover, both pyridoxal-5-phosphate dependent enzymes were inhibited by pyridoxine. In conclusion, the present study indicates that the neuropathy observed after taking a relatively high dose of vitamin B6 supplements is due to pyridoxine. The inactive form pyridoxine competitively inhibits the active pyridoxal-5'-phosphate. Consequently, symptoms of vitamin B6 supplementation are similar to those of vitamin B6 deficiency.
Hi Tim,
Based on your reading, what do you think the effects of B6 supplementation in individuals who DO respond well (i.e. do not display symptoms of B6 toxicity/deficiency, but whose other symptoms resolve when taking b6/p5p+cofactors)? Is it still damaging for these folks?
Hi Sarabeth,
Are you thinking about Pyroluria? When I researched that it all seemed like sound information but I remember reading the B6 and zinc amounts to supplement and immediately balking at the idea of doing that long term. It isn't the correct approach imo because it's not getting to the cause of the problem. Assuming pyroluria is a real condition what is the reason for these nutrient demands? Is the zinc and B6 creating some biochemical effect that alleviates the symptoms that has nothing to do with deficiency? Is the zinc and B6 compensating for a lack of something else? A lot of these ideas and therapies are fads to prey upon the sick and enrich naturopaths so it isn't in their interest to actually understand the condition, it is in their interest to have a condition they can charge people for for testing and treatment.
If you and your family have been taking a lot of B6 and it hasn't caused obvious problems I really don't think it's something that would have caused much harm. I would personally avoid supplementing with high amounts of anything long term as I don't think that is treating the cause. It's definitely something to be cautious about during pregnancy and conception as there is some talk of it having teratogenic effects.
...many people also got into toxicity with the active form of B6. And many have impaired conversion of B6 to the active form. B1 and especially B2 are cofactors to b6 conversion to p5p.
https://www.ncbi.nlm.nih.gov/pubmed/7814235
"Conversion of most naturally available vitamin B6 to its functional coenzyme pyridoxal 5'-phosphate (PLP) depends on riboflavin."
Some mercury toxic people need 100 mg and more of zinc daily and they do not become toxic...because mercury causes severe mineral disregulation. Most mercury toxic people need to take the active forms of vitamins because since mercury and heavy metals damage many of the enzymes required to convert them to the active forms.
There are diseases and metabolic disorders where the cause of the problem is treated for a long time and supplementation is the only option for these people. I read how some autistic children have to supplement specific amino acids because they are deficient and the only way for them is to supply these specific isolated amino acids.
I've always tested vitamins and minerals according to how I feel... If I feel well I take them, if there is a strong deficiency, the body always reacts.
I don't doubt that large amounts of P5P taken over an extended period of time could cause problems. If doses were close to amounts normally obtained from food I really doubt that P5P would be toxic. Say a P5P capsule contains 30 mg of it then that could be taken every 2 weeks.