Biological properties of vitamins of the B-complex, part 2 – vitamins B6 and B7 (biotin, vitamin H)

Nu i ion Resea ch Re iews
camb idge.o g/n
Re iew A icle
Ci e his a icle: Dias P, Sia ka T, Vop šalo á M,
Mo a co á M, Pou o á J, Pří a ská N,
K čmo á LK, Ja o ská L, and Mladěnka P
(2025). Biological p ope ies o i amins o he
B-complex, pa 2 – i amins B
6
and B
7
(bio in,
i amin H). Nu i ion Resea ch Re iews, page 1
o 34. doi: 10.1017/S0954422425100097
Recei ed: 9 Sep embe 2024
Re ised: 20 Ma ch 2025
Accep ed: 19 May 2025
Keywo ds:
bio in; essen ial; physiological; py idoxine;
oxici y
Abb e ia ions:
AI, adequa e in ake; CoA, coenzyme A; GABA,
gamma-aminobu y ic acid; IL, in e leukin; MCC,
me hylc o onyl-CoA ca boxylase; PLP,
py idoxal 50-phospha e; PLPBP, py idoxal
phospha e–binding p o ein; PNPO, py idoxine
phospha e oxidase; SMVT, sodium-dependen
mul i i amin anspo e ; TNF-α, umou
nec osis ac o α; TNSALP, issue non-speci ic
alkaline phospha ase
Co esponding au ho :
Přemysl Mladěnka;
Email: [email p o ec ed]
© The Au ho (s), 2025. Published by Camb idge
Uni e si y P ess on behal o The Nu i ion
Socie y. This is an Open Access a icle,
dis ibu ed unde he e ms o he C ea i e
Commons A ibu ion licence (h ps://
c ea i ecommons.o g/licenses/by/4.0/), which
pe mi s un es ic ed e-use, dis ibu ion and
ep oduc ion, p o ided he o iginal a icle is
p ope ly ci ed.
Biological p ope ies o i amins o he
B-complex, pa 2 – i amins B
6
and B
7
(bio in, i amin H)
Pa ícia Dias1, TomášSia ka2, Ma ie Vop šalo á1, Monika Mo a co á1,
Jana Pou o á1, Nikola Pří a ská3
,
4, Lenka Kujo ská K čmo á3
,
4,
Lenka Ja o ská3and Přemysl Mladěnka1
1Depa men o Pha macology and Toxicology, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y, H adec
K álo é, Czech Republic; 2Depa men o Pha macognosy, Facul y o Pha macy in H adec K álo é, Cha les
Uni e si y, H adec K álo é, Czech Republic; 3Depa men o Clinical Biochemis y and Diagnos ics, Uni e si y
Hospi al H adec K álo é, H adec K álo é, Czech Republic and 4Depa men o Analy ical Chemis y, Facul y o
Pha macy in H adec K álo é, Cha les Uni e si y, H adec K álo é, Czech Republic
Abs ac
Vi amins B
6
( ha is, py idoxin and i s analogues) and B
7
( ha is, bio in o i amin H) a e
essen ial molecules o many physiological p ocesses. In addi ion o hei well-known
in ol emen in se e al enzyma ic eac ions, ecen disco e ies e ealed hei pa icipa ion in
o he p ocesses, o example, in gene exp ession ia epigene ic p ocesses, such as bio inyla ion
o p o eins in he case o bio in. Plan s, ungi, a chaea and mos bac e ia syn hesise bo h
i amins, whe eas animals and humans lack enzymes o hei biosyn hesis and depend on hei
exogenous supply. A leas in he case o bio in, human gas oin es inal mic obio a can likely
pa ly sa is y he need. Bo h i amins a e wa e soluble and equi e a anspo e o e icien
abso p ion a e o al adminis a ion; hey can be apidly exc e ed; hence, hey a e conside ed
la gely non- oxic. In addi ion o physiological and kine ic aspec s o i amin B
6
and bio in, his
e iew, which is based on a sea ch in PubMed up o 2023, co e s sou ces o hese i amins, he
impac o ood ea men on hei con en , causes and symp oms o de iciency and speci ic
mu a ions ela ed o hei unc ion. Cu en ly a ailable li e a u e on he analy ical
de e mina ion o hese i amins in biological luids, possible pha macological uses and
symp oms o oxici y, al hough a e, a e also included.
In oduc ion
Vi amins o he B-complex ep esen wa e -soluble molecules wi h essen ial oles in humans.
The p esen e iew is a ollow-up o ou p e ious manusc ip , in which we summa ised he
biological p ope ies o he i amins B
1
,B
2
,B
3
and B
5
(1). He ein, we cen e on i amins B
6
and B
7
(bio in) o p o ide a comp ehensi e summa y o sou ces, p ope ies, physiological unc ions,
diso de s ha esul om hei de iciency and scien i ic in o ma ion, which has been o en
o e looked since hei disco e y. We sough o co e all signi ican s udies on he opic,
including cu en ends and po en ial di ec ions o u u e esea ch. Such a e iew has been
p e iously missing in he a ailable li e a u e.
Me hods
PubMed was used as he bibliog aphy da abase, and eligible publica ions we e selec ed om
1938 o 2023. The ollowing keywo ds we e added o he que y box: ( i amin B
6
AND
p ope ies) and ( i amin B
6
AND sou ces) and ( i amin B
6
AND pha macokine ics), ( i amin
B
6
AND physiological unc ion), ( i amin B
6
AND pha macological uses), ( i amin B
6
AND
oxici y). Ins ead o i amin B
6
, simila combina ions we e used wi h py idoxine, i amin B
7
and
bio in. The eligibili y c i e ia we e as ollows: pee - e iewed jou nal a icles o book chap e s
published in he English language. The e we e no exclusion c i e ia o he sea ch.
Vi amin B
6
An in oduc ion o i amin B
6
Vi amin B
6
, o dina ily bu imp ecisely known as py idoxine, is a gene al e m o wa e -soluble
py idine de i a i es wi h he same physiological ole. This i amin comp ises six ela ed
compounds – i ame s (Fig. 1a), ha is, py idoxine (o py idoxole, an alcohol), py idoxal (an
aldehyde), py idoxamine (an amine) and hei 50-phospha e es e s, such as py idoxal 50-
h ps://doi.o g/10.1017/S0954422425100097 Published online by Camb idge Uni e si y P ess
phospha e (PLP), py idoxamine 50-phospha e and py idoxine
50-phospha e. PLP is he biologically ac i e o m o i amin B
6
because i is a co ac o o mos i amin B
6
-dependen enzymes in
he o ganism(2,3).
Py idoxine was disco e ed in 1934 by Hunga ian physician
Paul Gyö gy and colleagues, and was isola ed in pu e o m sho ly
he ea e . Humans mus acqui e i om hei die . Mo eo e , PLP
can be ecycled om ood and deg aded i amin B
6
in he sal age
pa hway when he i amin unde goes in e con e sion inside cells
and yields di e en o ms, including ac i e PLP (Fig. 1b)(4,5).
Py idoxine, py idoxal and py idoxamine a e con e ed o hei
phospho yla ed o ms by he py idoxine/py idoxamine/py idoxal
kinase, while phospha ases hyd olyze phospho yla ed i amin B
6
i ame s. Py idoxine 50-phospha e and py idoxamine 50-phos-
pha e a e u he oxidised o he ac i e o m, PLP, by he enzyme
py idoxine (py idoxamine) phospha e oxidase.
Sou ces o i amin B
6
Na u al sou ces o i amin B
6
Plan s, ungi, a chaea and mos bac e ia syn hesise py idoxine,
whe eas animals and humans lack enzymes o i s biosyn he ic
pa hway and ely solely on he exogenous supply o he i amin(3,6–
27). Vi amin B
6
is widely dis ibu ed in oods o plan and animal
o igin. Whole g ains, bananas, po a oes, pulses, nu s, bee , po k,
poul y, o gan mea s and ish a e good sou ces o humans(28–50).
Some he bs and spices ( o example, ga lic, cu y, and ginge )(51),
some glu en- ee pseudoce eals ( o example, ama an h)(52)and
oyal jelly a e also ich in i amin B
6
(37,53). In animal-de i ed oods,
i amin B
6
is usually p esen in phospho yla ed o ms (mainly o
py idoxal and py idoxamine) and, o a lesse ex en , in he ee
o m(23,37,54–56). The e is limi ed in o ma ion on he bioa ailabili y
o i amin B
6
om animal p oduc s in humans. The bioa ailabili y
is es ima ed o be gene ally high and, in many cases, almos
Fig. 1. Chemical s uc u es o i amin B
6
,
including i s ac i e o ms, and i amin B
7
.
(a) S uc u e o he i ame s o B
6
.(b) Vi amin
B
6
sal age pa hway. PK, py idoxine/py idox-
amine/py idoxal kinase; PNPO, py idoxine phos-
pha e oxidase. (c) Chemical s uc u e o D(þ)-
bio in. The bio in molecule is composed o wo
ings: an imidazolidinone ing (blue) and a
e ahyd o hiophene g oup ( ed) a ached o a
ale ic acid moie y as a side chain (yellow).
2 P. Dias e al.
h ps://doi.o g/10.1017/S0954422425100097 Published online by Camb idge Uni e si y P ess
comple e. Howe e , he mal p ocessing educes i by 25–30%; and
he eac ion be ween py idoxal and py idoxal phospha e wi h he
ε-amino g oup o p o ein-bound lysine may be esponsible o he
dec eased bioa ailabili y(57–61). In plan -de i ed oods, he i amin
usually occu s as bo h ee py idoxine and in a glycosyla ed o m,
pa icula ly as py idoxine-β-
D
-glucoside, whose p opo ion can
ange depending on he plan species, om 5% o 75% o he o al
i amin con en (23,28,54,57,62–68). The glucoside is only pa ly clea ed
enzyma ically by hyd olases in he small in es ine, and i s
bioa ailabili y is abou 50% and 75% lowe han ha o ee
py idoxine in humans and a s, espec i ely, ha is o say, ha
appa en ly he capabili y o u ilising he glycosyla ed o m is
species speci ic. The con ibu ion o py idoxine-β-
D
-glucoside o
he o al i amin B
6
in ake in he a e age human die is a ound
15%, hence di e en ypes o ege a ian die do no pose a isk o
i amin B
6
de iciency. This ac is also suppo ed by indings om a
popula ion-based su ey compa ing he i amin B
6
s a us among
ege a ians, pesca a ians, lexi a ians and mea -ea e s. Howe e ,
indi iduals wi h a ma ginal in ake o o al i amin B
6
would be
mo e p one o educed nu i ional s a us due o his incomple e
bioa ailabili y(28,29,46,54,57,58,62,64,69–83). The absolu e bioa ailabili y
o i amin B
6
om a mixed die is es ima ed o be abou
75%(29,44,84–86).
Vi amin B
6
is also syn hesised in signi ican quan i ies by he
mic obio a o he human la ge in es ine, and his could ep esen a
seconda y exogenous sou ce o he i amin. Indeed, he exis ence
o a speci ic ca ie -media ed mechanism o py idoxine up ake in
human colonocy es was demons a ed. Con e sely, i is likely ha
a la ge po ion o he i amin p oduced by mic obio a is aken up
by non-syn hesising mic obes. The ex en o he con ibu ion o
mic obially p oduced i amin B
6
o o e all body le els is unclea as
he e a e no human s udies o p o ide e idence o i (22,28,29,37,87–93).
Amoun s o i amin B
6
in some selec ed oods u s a e shown in
Table 1.
An i i amins B
6
The die can also con ain an i i amin B
6
ha ei he compe e o
eac i e si es o i amin B
6
- equi ing enzymes o di ec ly inac i a e
he i amin(37,94). The bes -known an i i amin B
6
is p obably
ginkgo oxin (4’-O-me hylpy idoxine), which occu s in di e en
issues o he ee Ginkgo biloba, wi h he highes concen a ions
being p esen in seeds. Inges ion o ginkgo oxin can lead o
abdominal pain, epilep i o m con ulsions and loss o conscious-
ness due o he a o emen ioned in e e ence wi h i amin B
6
.As
seeds a e a ood sou ce in Sou heas Asia, including China, Japan
and Ko ea, and ex ac s om lea es a e used in pha maceu ical
p oduc s wo ldwide, hey ep esen a po en ial heal h isk(3,95–112).
Indeed, ginkgo oxin and i s de i a i es ound in he A ican ees
o he genus Albizia ( o example, A. anganyicensis,A. e sicolo ,
A. julib issin and A. lucida) a e he cause o poisoning o li es ock
(ca le and sheep): one o he mos impo an ag icul u al p oblems
in Sou h A ica(3,101,113). Flaxseed con ains he i amin B
6
an agonis s, 1-amino-
D
-p oline, and i s p ecu so , he dipep ide
lina ine. Thei possible dele e ious e ec s h ough he consump-
ion o laxseed dese e a en ion in indi iduals wi h mode a e
i amin B
6
s a us(94,114–118). Gy omi in (N-me hyl-N- o mylhy-
d azone) om he oxic mush oom Gy omi a esculen a (genus
Gy omi a is also known as alse mo el) is con e ed o (mono)
me hylhyd azine a e inges ion, which is able o inhibi py idoxal
kinase and hence deple es i amin B
6.
In oxica ion usually occu s
abou 10 h a e he inges ion o esh o d ied mush ooms. I gi es
ise o poisoning symp oms such as con usion and seizu es.
Table 1. Vi amin B
6
con en in selec ed oods u s
Food
Vi amin B
6
con en
(μg/100 g) Re e ences
Oa 120–960 (47,650,651)
Whea 127–407 (45,47,138,139,142,190,203,272,650–652)
Rice, b own 123–563 (142,143,148,149)
Rice, whi e 93–161 (142,143,148,149)
Maize 307–620 (47,142,145,650,651)
Rye 202–290 (47,138,650,651)
Ba ley 231–1100 (47,138,650,651)
Mille 380 (650)
So ghum 170−590 (653)
Soybean 267–550 (80,654,655)
Len il 540 (476)
Peanu 260–350 (654,656,657)
Macadamia nu 218–300 (196,658)
Pis achio nu 1032–1700 (47,196,654,658)
Hazelnu 378–600 (47,196,658)
Walnu 443–540 (47,196,654,658)
Almond 100–188 (80,196,654,658,661)
Ga lic 1240 (476)
Po a o 140–345 (47,142,188)
Ca o 60–206 (47,80,188)
Cabbage 65–140 (47,188)
Toma o 60–65 (47,188)
B occoli 130–190 (47,188)
Cauli lowe 140–170 (47,188)
Spinach 120–227 (47,188)
O ange 83–88 (47,80)
A ocado 290 (662)
S awbe y 30 (47,188)
Apple 56–104 (47,80,188)
Pea 14–40 (47,188)
Whi e b ead 16–80 (80,143,190,663,664)
B own b ead 79–170 (80,143,190,663,664)
Po k 370–540 (31,39,142,476,665)
Bee 264–579 (31,38,39,142,476)
Chicken b eas 330–811 (476,666,667)
Li e , bee 840–1080 (39,476)
Li e , po k 690 (39,476)
Tuna 430 (668)
Sa dines 310 (668)
Bake ’s yeas s 430 (476)
Oys e mush oom 100–110 (476,669)
Bu on mush oom 50–77 (208,476,669)
(Con inued)
Biological p ope ies o i amins o he B-complex 3
h ps://doi.o g/10.1017/S0954422425100097 Published online by Camb idge Uni e si y P ess
In e es ingly, du ing cooking, me hylhyd azine ola ilises, and
poisoning occu s also a e inhala ion o hese apou s(118–122).
Simila ly, aga i ine con aining a hyd azinic moie y in i s s uc u e
is a oxic p inciple o a ious Aga icus species, o example, he
edible bu on mush oom Aga icus bispo us(118,121,123). The con en
o bo h oxins in ungi may be dec eased by p ocessing, such as
boiling in wa e , d ying and eezing(121,124,125). O he na u al
i amin B
6
an agonis s, which a e o li le signi icance o human
nu i ion, a e oxic non-p o einogenic amino acids occu ing in
some leguminous plan s: mimosine in Mimosa and Leucaena
species, and cana anine and canaline in Cana alia spe-
cies(118,126–132).
E ec s o ood p ocessing on i amin B
6
con en
Food p ocessing is he ans o ma ion o ag icul u al p oduc s in o
oods o human consump ion. P ima y p ocessing is he
con e sion o he inedible aw p oduc s in o ood ing edien s.
Seconda y p ocessing in ol es he con e sion o ood ing edien s
in o edible oods. Te ia y p ocessed oods a e comme cially
p epa ed oods. P oduc s om p ima y p ocesses make up he
majo pa o he human die as hey a e ei he consumed aw o
used as ing edien s in seconda y and e ia y p ocesses(133). Food
p ocessing may al e he i amin B
6
con en (134,135). A ough
o e iew o he majo da a on i amin B
6
losses in some ood
g oups due o p ocessing is p esen ed in Supplemen a y Table S1
in he Supplemen a y Da a. Mo e da a on speci ic oods,
in o ma ion on condi ions and commen s a e in he ex below.
Milling and e ining o ce eals
The p ima y p ocessing o ce eals (milling and e ining) ha
sepa a es he b an and ge m, which a e ich in mic onu ien s,
om s a chy endospe m causes a conside able loss o i amin
B
6
(136–141). Milling educes he alue o he i amin B
6
con en in
maize by 65–75%(137,142–146). The i amin B
6
con en dec eases by
66–89% in whi e whea lou , compa ed wi h wholeg ain
lou (45,136–138,142–144,147). The con en o i amin B
6
is likewise
64% and 79.5% lowe in e ined han in wholeg ain ye and
so ghum lou , espec i ely.(144). Vi amin B
6
losses in non-
pa boiled and pa boiled whi e ice a e 42–86% and 12–26%,
espec i ely, compa ed wi h b own ice. The decline in i amin B
6
in pa boiled ice is lowe , in con as o he non-pa boiled one,
because a pa o he i amin di uses om he i amin- ich ou e
b an laye in o he endospe m du ing he pa boiling p ocess ha
akes place be o e milling(68,137,142,143,148–152). The seconda y
p ocessing o ce eals, such as b eadmaking, ice cooking and
nix amalisa ion o maize, b ings on addi ional i amin B
6
losses.
They a e discussed la e (‘P ocessing o plan -based oods’).
P ope ies o i amin B
6
and mechanisms o i amin loss
du ing ood p ocessing
Vi amin B
6
loss du ing p ocessing and s o age o ood can occu in
se e al ways. Being soluble in wa e , leaching is one o he p incipal
causes. Vi amin B
6
in oods is s able unde acidic condi ions bu
uns able in neu al and alkaline en i onmen s, pa icula ly when
exposed o hea o ligh . The acidic aqueous solu ions o i amin B
6
may be hea ed wi hou decomposi ion, as i amin B
6
is des oyed
by ul a iole adia ion in neu al o alkaline solu ions bu no in
acidic solu ions. Vi amin B
6
is no mally s able o oxygen. O he
se e al i ame s, py idoxine is a mo e s able han py idoxal and
py idoxamine. The e o e, he p ocessing losses o i amin B
6
end
o be highly a iable, wi h plan -de i ed oods (con aining mos ly
py idoxine) losing li le o he i amin, and animal p oduc s
(con aining mos ly py idoxal and py idoxamine) associa ed wi h
highe losses(37,59,87,132,134,135,147,153–166).
P ocessing o animal-based oods
Boiling, s ewing, oas ing and ying educe he i amin B
6
con en
by 55%, 33–58%, 30% and 40–45%, espec i ely, in po k; by 60–
77%, 55–57%, 40% and 55–58%, espec i ely, in bee ; and by 40–
58%, 40–47%, 50% and 45–56%, espec i ely, in chicken,
depending on cooking empe a u e and ime(161,167–171). In whole
mea dishes, including cooking liquid, g a y, juice o soup, abou
15–20% mo e i amin B
6
emains, owing o e en ion o he
i amin ha leached in o he wa e phase(168,170,172–174). F ied
b eaded mea s con ain 5–35% mo e i amin B
6
han hose wi hou
b eading, which may assis in apping he liquid and, he e o e,
dec easing he loss o wa e -soluble i amins(170,175). Abou 9% o
i amin B
6
was los om po k and bee when he d ip exuding om
he ozen mea du ing hawing was disca ded(176,177). The cooking
loss o i amin B
6
in ish mea (gil head seab eam, ancho y and
A lan ic boni o) was 55–85% and 60–89% when g illed and baked,
espec i ely, due o he mal deg ada ion and leakage o he i amin
in he los wa e (178). Hea -induced educ ion o i amin B
6
in milk
is usually 5–20%, 5–10%, 5–20%, 10–50% and 40% o boiled,
pas eu ised, ul a-high empe a u e ea ed, s e ilised and con-
densed milk, espec i ely, compa ed wi h aw milk(134,170,179–184).
Ha d cooked, poached, sc ambled, baked and ied eggs lose 20–
23%, 15%, 10%, 10% and 10% o i amin B
6
du ing cooking,
espec i ely(170,185,186).
P ocessing o plan -based oods
Boiling, s eaming and ying lead usually o a i amin B
6
loss o 30–
35%, 15% and 10%, espec i ely, in ege ables alone, and o ha o
abou 10% when aking he o al dish in o accoun (168,170).In
chickpeas, mic owa e cooking, au ocla ing and boiling caused a
decline o 19%, 34% and 42% in i amin B
6
con en , espec-
i ely(187). The amoun o i amin B
6
in po a oes is educed by 30–
57%, 21% and 10% du ing boiling, baking and deep ying,
espec i ely(161,169,188). The way o cooking ice in luences he
con en o i amin B
6
. In di e en ice a ie ies, he boiling
cooking me hod (cooking ice wi h ex a wa e and hen
elimina ing he wa e ) led o i amin losses o 3–74%, compa ed
wi h he adi ional cooking me hod (cooking wi h a cons an
amoun o wa e wi hou emo ing he wa e )(189). Du ing
b eadmaking, he i amin B
6
con en dec eased on a e age by
33% and 62% in whole and whi e whea b ead, espec i ely, in
compa ison wi h whole and whi e whea lou (190,191). Simila
Table 1. (Con inued )
Food
Vi amin B
6
con en
(μg/100 g) Re e ences
Milk 35–60 (48,142,467,670)
Yoghu 87–100 (467,670)
Cheese, chedda 69 (476)
Eggs 130–241 (48,142,185)
4 P. Dias e al.
h ps://doi.o g/10.1017/S0954422425100097 Published online by Camb idge Uni e si y P ess
esul s we e ob ained du ing ye sou dough b ead p oduc ion(192).
Toas ing whea b ead induced an inc ease in i amin B
6
by 75%
due o i s elease om glycosidic bound o ms(191). E ec s o
ex usion echniques on i amin B
6
e en ion in ce eal g ains
showed a educ ion o 0–23% and o 65% in maize g i s and oa
whole g ains, espec i ely(193). D ying o a hana, a adi ional
Tu kish e men ed ce eal ood, esul ed in i amin B
6
losses o 3%,
16% and 23% a empe a u es o 50 °C, 60 °C and 70 °C,
espec i ely(194). A dec ease in i amin B
6
con en in nu s a ied
om 2–7.5% in almonds, up o 4–34% in pis achio nu s a e
oas ing(195,196). Alkali-p ocessing o co n g ains o masa (nix am-
alisa ion) esul ed in a loss o 23% o i amin B
6
(145). The highly
a iable con en o i amin B
6
in bee is a ec ed by se e al ac o s,
including aw ma e ials and he b ewing p ocess(197–199).
Ge mina ion is an e ec i e way o imp o e he nu i ion alue
o edible seeds: inc eases o 54%, 78% and 26% in i amin B
6
con en occu ed in ge mina ed len ils(200), ough ice(201)and aba
beans(202), espec i ely. Con e sely, i amin B
6
le els dec eased by
11%, 13% and 50% in ge mina ed whea (203), b own ice(201)and
so ghum(204), espec i ely, a e ge mina ion.
Food p ese a ion and s o age
Canning, a ood conse a ion me hod, b ough on a i amin B
6
educ ion o 46%, 34%, 31% and 18% in mush ooms, whole peeled
oma oes, whi e aspa agus and len ils compa ed wi h hei
espec i e unp ocessed p oduc s(205). Ionising i adia ion, a
me hod used o ood p ese a ion, has a low e ec on i amin
B
6
; losses anging om ze o in whea o abou 15% in ish we e
obse ed(206,207).
The amoun o i amin B
6
in bu on mush ooms signi ican ly
declined by 23% and 45% a e 6 and 12 mon hs, espec i ely,
du ing ozen s o age a −20 °C(208). The con en o i amin B
6
dec eased g adually in asep ically packaged ul a-high empe a u e
ea ed milk du ing s o age a oom empe a u e, esul ing in a
96% loss a e 20 weeks(183). No ema kable changes and a 20%
decline in i amin B
6
con en happened in acuum-packaged
b occoli au g a in and salmon, espec i ely, s o ed a oom
empe a u e, ei he on he Ea h o exposed o space ligh o 880
d; he i amin con en in ligh samples did no deg ade as e han
ha o g ound con ols(209). The in es iga ion o he in luence o
s o age condi ions on i amin B
6
e en ion in a eeze-d ied una
mo nay meal (con aining una, ege ables and pas a) o i ied wi h
ha i amin showed a mean dec ease o 14% in he i amin
ollowing s o age a empe a u es o 1 °C, 30 °C and 40 °C o up o
24 mon hs(210). The i amin B
6
losses in meals in wo hospi al
oodse ice sys ems, he cook/ho -hold sys em, whe e ood is held
ho om he ime o cooking o se ice, and he cook/chill sys em,
whe e he cooked ood is chilled, s o ed and ehea ed, ha e also
been summa ised and compa ed(211).
Indus ial p oduc ion o i amin B
6
Py idoxine hyd ochlo ide, which is mainly used in pha maceu ical
p epa a ions, die a y supplemen s and as an addi i e in ood and
eed, is manu ac u ed by chemical syn hesis(29,37,60,84,87,158,212–219).
All p esen -day indus ial i amin B
6
syn heses use he Diels–Alde
eac ion o a diene (4,5-subs i u ed oxazoles) and a dienophile
(alkyldioxepins) as a key s ep(158,220–225). An al e na i e o he
cu en chemical p ocesses migh be en i onmen ally sus ainable
biop ocesses based on mic obial i amin B
6
e men a ion, which is
o g ea in e es o he bio echnological indus y. Se e al a emp s
ha e been made o cons uc o e p oducing s ains by gene ic
enginee ing o mic oo ganisms such as Sino hizobium melilo i,E.
coli and Bacillus sub ilis. Un o una ely, p oduc ion le els a e oo
low and a e no cos e ec i e. The e o e, majo me abolic
enginee ing e o s a e s ill equi ed o de eloping e men a ion
p ocesses ha could ou compe e he chemical syn hesis o i amin
B
6
. The main bo lenecks a e insu icien ac i i ies o some
enzymes in he biosyn he ic pa hway and accumula ion o oxic
in e media e me aboli es(226–237).
Food o i ica ion and bio o i ica ion wi h i amin B
6
Food o i ica ion is de ined as he p ac ice o delibe a ely adding an
essen ial mic onu ien o ood ha is commonly consumed by he
gene al popula ion wi h he in en ion o imp o ing he nu i ional
quali y o he ood supply and p o iding a public heal h bene i wi h
minimal isk o heal h(238–240). Foods o i ied wi h i amin B
6
,
simila ly o die a y supplemen s, cons i u e an addi ional die a y
sou ce o he i amin(60,150,241–246).O e all, i aminB
6
de iciency
is a e in he gene al heal hy popula ion(8,29,44,150,243,246–250).I
may be a conce n in high-income as well as low-income
coun ies in ce ain g oups(142), such as olde adul s(245,251–254),
people o low socio-economic s a us and hose expe iencing ood
insecu i y(142,241,244,245,250). As o 2022, some coun ies, mos ly
bu no solely loca ed in A ica, ha e manda o y o i ica ion o
whea lou (mos o en), maize lou and/o ice wi h i amin B
6
(Nica agua, Panama, Cuba, Pe u, Jo dan, Pales ine, Nige ia,
Chad, E hiopia, Kenya, Uganda, Rwanda, Bu undi, Tanzania,
Mozambique, Zimbabwe and Sou h A ica)(255–257).The eisa
olun a y o i ica ion wi h i amin B
6
in many o he coun ies,
such as he USA, he Dominican Republic, Eswa ini, India,
Bangladesh,Myanma , heUKandcoun ieso heEu opean
Union; he i amin is added o a ious oods, such as a a, maida,
ice, b eak as ce eals, be e ages and ce eal-based oods o
in an s and young child en(28,60,142,150,217,255,256,258–265).
Bio o i ica ion is a p ocess o inc easing he densi y o
mic onu ien s ( i amins and mine als) in a c op and comp ises
(sensu s ic o, ha is, omi ing ag onomic p ac ices) con en ional
plan b eeding and gene ic enginee ing app oaches. I di e s om
o i ica ion because i aims o make plan oods na u ally mo e
nu i i e a he han adding nu ien s o he oods du ing ood
p ocessing. Bio o i ica ion is an ideal s a egy o imp o e
nu i ion o u al and poo communi ies ha ely on subsis ence
a ming o nu i ion o may no ha e access o di e se die s,
supplemen s and o i ied oods. Bio o i ica ion complemen s
exis ing in e en ions and may help by inc easing he daily
adequacy o mic onu ien in ake among he mos ulne able
mic onu ien de icien people(142,239,266–268). Vi amin B
6
is de no o
syn hesised by plan s, and he e o e, bio o i ica ion could be a
p omising ou e o enhance ood quali y by inc easing he i amin
le els in plan s in he u u e(8,269–271). Analysis o he na u al
di e si y o i amin B
6
con en in whea , ice and po a o
ge mplasm has shown limi ed a ia ion, so b eeding s a egies
do no seem o be adequa e o inc ease he i amin con en in hose
c ops(68,142,272,273), in con as o maize, whe e ema kable wide
anges in i amin B
6
le els among a ious geno ypes we e ecen ly
epo ed(274). Mos e o s o da e ha e used gene ic enginee ing
app oaches. Biosyn hesis o i amin B
6
is p ima ily con olled by
wo enzymes, making i amin B
6
bio o i ica ion an a ac i e
a ge o plan gene icis s. O e exp ession o genes encoding one
o bo h enzymes leads o he enhanced accumula ion o i amin B
6
in ansgenic plan s compa ed wi h he un ans o med ones: 0·86–
1·25- old in obacco plan s, 1·45–4- old in A abidopsis seeds, 0·16–
34·96- old in whea seeds, 1·6–3·9- old in ice seeds, 3–16- old in
cassa a oo s and 1·07–1·5- old in po a o ube s. In e es ingly,
Biological p ope ies o i amins o he B-complex 5
h ps://doi.o g/10.1017/S0954422425100097 Published online by Camb idge Uni e si y P ess

enhancing i amin B
6
le els in plan s may also posi i ely a ec
hei ole ance o en i onmen al s ess(27,142,268–270,275–280). All
bio o i ica ion a emp s e ealed he easibili y o aising he
i amin B
6
amoun s in plan s. So a , he i amin B
6
con en s in
ansgenic plan s a e low and highly a iable. Rega dless, mo e
esea ch o unde s anding he egula o y mechanisms ha
con ol genes in ol ed in he biosyn hesis and me abolism o
i amin B
6
in plan s is needed(225,269).
Pha macokine ics o i amin B
6
The o al con en o i amin B
6
in he adul human body is abou
170 mg(281).B
6
i ame s a e abso bed in he uppe small in es ine
(jejunum) om die and/o o al supplemen s. In addi ion o he
die a y sou ces o he i amin, humans migh also ecei e i amin
B
6
om bac e ial mic obio a in he la ge in es ine as men ioned
ea lie (88,282,283). All i amin B
6
analogues, ha is, py idoxine,
py idoxamine, and py idoxal, a e p esen in he die .
Phospho yla ed o ms unde go dephospho yla ion by means o
phospha ases p io o abso p ion in o epi helial cells and p io o
elease in o he po al sys em. Phospho yla ed o ms a e poo ly
di usible and, in ac , hey a e apped in cells and a
dephospho yla ion s ep is necessa y o hei e lux. The
bioa ailabili y o i amin B
6
om supplemen s is abou 95%,
whe eas he bioa ailabili y o py idoxin, py idoxal and py idox-
amine is simila . The p esence o ib e in plan sou ces educes
bioa ailabili y by 5–10%, while he p esence o py idoxine
glucoside educes bioa ailabili y by 75–80%. On a e age, he
bioa ailabili y o i amin B
6
om a mixed die can be es ima ed o
be abou 75%. In ac , abso p ion in he in es ine is media ed bo h
ia passi e di usion ( ha is, a la ge amoun is eadily abso bable
wi hou cell sa u a ion) and a ca ie media ed mechanism ( ha is,
a sa u able mechanism). In humans, he e is ca ie -media ed
anspo o B
6
i ame s ia he i amin B
1
( hiamine) anspo e s
THTR1 and THTR2, which belong o he SLC19A2 and SLC19A3
amilies(284). The maximum concen a ion (C
max
) o py idoxine is
usually achie ed wi hin 5·5h
(285,286). In he li e , all o ms o
dephospho yla ed i amin B
6
a e ephospho yla ed and inally
con e ed o py idoxal 50-phospha e in hepa ocy es. Se e al
enzymes, such as ATP-dependen py idoxine/py idoxamine/
py idoxal kinase, phospha ases and la in mononucleo ide–
dependen py idoxine phospha e oxidase (PNPO) a e in ol ed
in hese eac ions. PNPO con e s py idoxine 50-phospha e
(PNP) and py idoxamine 50-phospha e (PMP) in o py idoxal
50-phospha e (PLP) (Fig. 1b).
Py idoxal phospha e u he binds o albumin in he li e , and
i is eleased in o he ci cula ion, whe e i o ms app oxima ely
60% o o al ci cula ing B
6
,wi hlesse amoun so all h ee
dephospho yla ed o ms. A e dissocia ion om albumin and
dephospho yla ion by alkaline phospha ase, ee py idoxal is
aken up by e y h ocy es and hen apped inside cells in he o m
o PLP(287–292).
Plasma PLP is he mos common pa ame e o de e mina ion
o i amin B
6
s a us. I s usual concen a ion is mo e han 30 nM in
adul s(5). PLP is u ilised as a co ac o o many enzymes ela ed o a
ow o me abolic pa hways(293,294), as will be discussed la e .
Ci cula o y PLP passes in o b eas milk, and also c osses
physiological ba ie s such as he placen al and blood–b ain
ba ie s. The same mechanism, as in o he o gans, is desc ibed o
b ain en y and s o age, ha is, ini ial dephospho yla ion in he
blood–b ain ba ie by means o issue non-speci ic alkaline
phospha ase (TNSALP), ollowed by up ake and en apping o he
i amin in neu ons a e phospho yla ion o PLP(295).
The majo inac i e me aboli e o PLP is 4-py idoxic acid. I is
o med in he li e and exc e ed in he u ine (Fig. 2). U ina y
exc e ion o his me aboli e g ea e han 3 mmol/d can be used as a
ma ke o adequa e sho - e m i amin B
6
s a us. I s hal -li e
appea s o be 15–20 d(296).
The e is no a la ge s o age o i amin B
6
in issues, p obably
owing o he ac ha humans equi e only small amoun s o
i amin B
6
om ood sou ces, since he biologically ac i e o m,
PLP, can be o med no only by in e con e sion om di e en B
6
i ame s bu also using he co ac o s om deg aded enzymes in he
sal age pa hway.
Physiological unc ion o i amin B
6
The ac i e o m o i amin B
6
, PLP, ac s as a coenzyme in mo e
han 140 di e en enzyma ic eac ions necessa y o i al cellula
p ocesses(8). This unc ion is enabled by he highly eac i e
aldehyde g oup o PLP, ha o ms Schi bases wi h he εamino
g oups o lysine esidues a he ac i e cen es o PLP-dependen
Fig. 2. Pha macokine ics o i amin B
6
. The
igu e summa ises he pha macokine ics o
i amin B
6
in he human body. PN, py idoxine;
PNP, py idoxine 50-phospha e; PL, py idoxal;
PLP, py idoxal 50-phospha e; PM, py idoxamine;
PMP, py idoxamine 50-phospha e; TNSALP, is-
sue non-speci ic alkaline phospha ase; BB,
blood–b ain ba ie .
6 P. Dias e al.
h ps://doi.o g/10.1017/S0954422425100097 Published online by Camb idge Uni e si y P ess
enzymes. Con e sely, binding o lysine esidues on some ho monal
ecep o s is esponsible o ansc ip ional modula ion. Mo eo e ,
he aldehyde g oup can eac wi h o he amino acids in p o eins,
especially wi h cys eine o his idine(297).
PLP is in ol ed in a ious pa hways, such as:
•Some s eps du ing he me abolism o amino acids, o
example, ansamina ion, deca boxyla ion and acemisa ion
p ocesses. Me abolic ans o ma ion o sulphu -con aining
amino acids, o example, he con e sion o me hionine o
cys eine h ough he key in e media e homocys eine o
S-adenosylme hionine. Ele a ed le els o ci cula ing homo-
cys eine in he blood a e associa ed wi h an inc eased isk o
ca dio ascula diseases, and S-adenosylme hionine is a
me hyl dono o many me hyla ion eac ions, o example,
me hyla ion o p o eins, DNA and RNA, and o he s(298–301).
In addi ion, cys eine syn hesised by his anssul u a ion
pa hway is an impo an con ibu o o glu a hione syn hesis,
which plays a ole in oxida i e s ess and he an ioxidan
de ense sys em.
•Some p ocesses du ing ca bohyd a e me abolism, o
example, he deg ada ion o s o ed ca bohyd a es such as
glycogenolysis, as PLP is a co ac o o glycogen phospho-
ylase. PLP also plays a ole in he eac ions ha gene a e
glucose om amino acids in he p ocess known as
gluconeogenesis(302–304).
•Lipid me abolism, especially biosyn hesis o sphingolipids,
which a e impo an o myelin o ma ion and hei
b eakdown(305).
•Biosyn hesis o many neu o ansmi e s, pa icula ly he
o ma ion o se o onin om yp ophan and he syn hesis o
epineph ine (ad enaline), no epineph ine (no ad enaline)
and dopamine (3,4-dihyd oxyphene hylamine) om phenyl-
alanine and y osine. PLP also con ols he o ma ion and
egula ion o he inhibi o y ansmi e γ-aminobu y ic
acid (GABA) in he b ain, and he neu omodula o
se ine(84,306–309).
•Ca abolism o yp ophan and i s con e sion o niacin,
ha equi es kynu eninase, which also necessi a es i amin
B
6
(310–313).
•Biosyn hesis o e apy oles ( o example, haem). PLP is
needed o he enzyma ic eac ion using succinyl-CoA and
glycine o gene a e δ-aminole ulinic acid, an in e media e
p ecu so in e apy ole biosyn hesis(314,315).
•Immune and in lamma o y pa hways, especially egula ion
o cy okine p oduc ion, pa icula ly in e e ons and
in e leukin 6(316,317).
Besides he ole o PLP as a co ac o in biochemical eac ions,
i amin B
6
also plays o he impo an oles in non-enzyma ic
unc ions, o example:
•PLP inhibi s enhancemen in gene exp ession by s e oid and
hy oid ho mones, and i amins A and D by binding o lysine
esidues in ho mone– ecep o complexes(318,319).
•An ioxida i e ac i i y by sca enging eac i e oxygen species
and chela ing o edox-ac i e me al ions(320–322).
Vi amin B
6
de iciency and ela ed diso de s
Se e e i amin B
6
de iciency esul ing om inadequa e in ake
(especially om die a y de ici ) is a e in he heal hy gene al
popula ion. Hypo i aminosis is usually ound in associa ion wi h
o he B i amin de iciencies, such as hose o olic acid ( i amin B
9
)
and i amin B
12
. As a o emen ioned, i should be emphasised ha
die a y i amin B
6
de iciency can occu in elde ly people (aged 65
yea s and o e )(323). Seconda y i amin B
6
de iciency is mos ly a
esul o gene ic diso de s o d ug in e ac ions(324,325).
Owing o he in ol emen o i amin B
6
in many me abolic
pa hways, a lack o su icien amoun s o i amin B
6
i ame s
causes a ious biochemical changes and may lead o signi ican
heal h p oblems. In pa icula , PLP is essen ial in he syn hesis and
me abolism o amino acids and neu o ansmi e s. Loss o
unc ion o he PLP-dependen enzyme glu ama e deca boxylase
leads o dec eased le els o he inhibi o y neu o ansmi e GABA.
Vi amin B
6
de iciency in humans is associa ed wi h sebo heic
de ma i is and cheilosis (including c acks a he co ne s o he
mou h), glossi is wi h ulce a ion, anaemia, senso y polyneu op-
a hy, dep ession, dec eased immune unc ion and inc eased isk o
ca dio ascula diseases. In child en, cha ac e is ic symp oms o
de iciency a e abno mali ies in hea ing and seizu es.(84)Seizu es
a e he esul s o an imbalance be ween exci a o y (glu ama e) and
inhibi o y (GABA) neu o ansmi e s(326–328).
In he popula ion, he e a e ce ain g oups o people a
inc eased isk o i amin B
6
inadequacy. People wi h impai ed
abso p ion, especially due o malabso p ion synd omes (usually
associa ed wi h C ohn’s disease and ulce a i e coli is) and a e
ba ia ic su ge y, ha e low i amin B
6
le els. Pa ien s wi h enal
disease, p edominan ly wi h ch onic enal insu iciency unde -
going dialysis, and li e disease end o ha e low plasma PLP
concen a ions. Also, alcoholics need i amin B
6
supplemen a ion
because alcohol is me abolised o ace aldehyde, which dec eases
PLP o ma ion in cells and compe es wi h PLP o p o ein binding.
Addi ional g oups a isk o i amin inadequacy despi e adequa e
die a y in akes a e no solely elde ly pe sons bu also hose wi h
au oimmune diso de s ( o example, heuma oid a h i is), hose
who a e obese and in p egnancy, o hose who a e aking o al
con acep i es(329–332). Analy ical me hods o he de ec ion o
i amin B
6
a e summa ised in Table 2. Mo e de ails a e shown in
Supplemen a y Da a Table S2, which e alua es indi idual speci ic
me hodologies wi h he ele an ci a ions om which he
in o ma ion was ob ained.
Py idoxine-dependen epilepsy
Py idoxine-dependen epilepsy (py idoxine-dependen seizu es,
i amin B
6
- esponsi e epilepsy) is a a e inhe i ed me abolic
disease cha ac e ised by ecu en seizu es wi h hei onse usually
in p ena al, neona al and pos na al pe iods o in childhood.
Seizu es a e caused p ima ily by low le els o GABA due o PLP
de iciency, ne e heless, o he abno mali ies a e in ol ed, o
example, low le els o adenosine and me hionine cycle de ec s.
This ype o epilepsy esponds o high in a enous doses o i amin
B
6
, ei he as py idoxine o as i s ac i e o m PLP, bu a e esis an
o con en ional an iepilep ic d ugs(333). Dec eased PLP a ailabili y
in his disease is caused by mu a ions in some genes in ol ed in
i amin B
6
me abolism, o example:
•Mu a ions in ALDH7A1, a gene encoding an iqui in, he
enzyme wi h α-aminoaddipic semialdehyde dehyd ogenase
ac i i y, in ol ed in lysine deg ada ion. An iqui in de iciency
leads o he accumula ion o he oxic lysine in e media es α-
aminoadipic semialdehyde and 1-pipe ideine-6-ca boxylic
acid, inac i a ing PLP by chemical complexa ion(334–336).
•Mu a ions in he ALDH4A1 gene occu ing in me abolic
disease hype p olinaemia II causes he o ma ion o
Biological p ope ies o i amins o he B-complex 7
h ps://doi.o g/10.1017/S0954422425100097 Published online by Camb idge Uni e si y P ess
Table 2. Summa y o analy ical me hods o he assessmen o i amins B
6
and B
7
in biological luids
Technique Sensi i i y (nM) Analy es Ma ix Ad an ages Disad an ages Re .
Publica ion
yea
LC-MS 0·1–127·51 ×103B
6
,B
6
-PL,
B
6
-P5P,
B
6
-PM, B
7
,
B
6
-PA,
B
6,7,9
and i s
i ame s,
me aboli es
and o he s
* Human milk
* Se um
* Whole blood
* Plasma
* Mice b ain
samples
* Tea s
* Faeces
Usually sho analysis ime, small sample
olume (30–250 μl), using MRM in
de ec ion, simple me hods o a ious
ma ices
Some me hods ha e complica ed sample
p epa a ion (b eas milk) and complica ed g adien
elu ion, some me hods use SIM and a e no ully
alida ed
(671,353)2012–2024
HPLC-FLD 0·3–20 B
6
-P5P, B
6
-PL,
B
6
-PA and
o he s
* Whole blood
* Ce eb ospinal
luid
* Se um
Me hods use small sample olume (100–
250 μl) and some o hem simple
de i a isa ion p ocedu e
Me hods ha e no IS included, usually complica ed
sample p epa a ion, long analysis ime wi h pos
column de i a isa ion
(672,357)2004–2020
HPLC-PDA
2D-LC-UV
0·1–7·29 ×103B
6
,
B
6
-PL, B
6
-P5P,
B
6
-PA and
o he s
* U ine
* Plasma
* Animal plasma
Me hods use small sample olume (60 μl) Me hods do no ha e op imal eco e y, he e is a
long analysis ime, poo sensi i i y, de i a isa ion,
complica ed sample p epa a ion, and no IS
(673,359)2014–2023
MLC-PDA 0·177 ×103B
6
* Plasma Me hod has simple sample p epa a ion No IS is used (674)2021
Senso s/
nanodo s /
CL/FLD/ECD
5–9·06 ×103B
6
,B
6
-PL, B
7
,
and o he s
* Se um
* U ine
* Plasma
* Whole blood
* A i icial u ine
Usually simple sample p epa a ion, small
sample olume (10 μl) and small sol en
consump ion, low p ice, some me hods
use common sc een-p in ed ca bon
elec ode
S anda d addi ion me hod is no sui able in clinical
analysis, necessi y o elec ode, nanocomposi e o
ca bon nanoshee p epa a ion, echnique is
esea ch only –no comme cially a ailable,
elec odes a e p epa ed in labo a o y, highe
de ec ion limi s compa ed wi h modi ied elec odes,
some me hods use la ge sample olumes (10 ml)
(675,370)2018–2023
Mic obiological
es ki s
2·87−14·57 B
6
-P5P
B
7
* Se um Small sample olume (50 μl) High p ice (wo king in duplica e ecommended),
usually long analysis ime (24 h), ATBs in pa ien s’
sample could in luence esul s
(676,372)
HPLC-FLD ki s 1·62–4·21 B
6
-P5P, and
o he s
* Plasma
* Whole blood
* Se um
Small sample olume (100–300 μl) No IS is used, long analysis ime, di e en
ex ac ion p ocedu es o each i amin, di e en
analysis condi ions ( empe a u e e c.), high p ice
o small sample se ies
(677,374)2021
LC-MS/MS ki s 1·5–6·96 B
6
-PL, B
6
-P5P,
and o he s
* Whole blood Me hods use IS, MRM, he e is sho
analysis ime, small sample olume (50 μl)
combined wi h simple sample
p epa a ion
High p ice o small sample se ies (678)2021
ELISA ki s 0·13−51·16 ×10−3B
7
* Se um
* Plasma
* U ine
Me hods use small sample olume (50–250
μl). One ki is sui able o a ious
ma ices, high sensi i i y
Me hods a e o esea ch only, c oss- eac i i y wi h
analogues, ime consuming me hods wi h high
p ice o small sample se ies
(679,377)2021
B
6
, py idoxine; B
6
-PL, py idoxal; B
6
-P5P, py idoxal-5-phospha e; B
6
-PM, py idoxamine; B
6
-PA, py idoxic acid; B
7
, bio in; B
9
, olic acid; ATB, an ibio ic; CL, chemiluminescence; ECD, elec ochemical de ec ion; ELISA, enzyme-linked immunoso ben assay; FLD,
luo escence de ec ion; HPLC, high pe o mance liquid ch oma og aphy; IS, in e nal s anda d; LC-MS, coupling o liquid ch oma og aphy and mass spec ome y; MLC, micella liquid ch oma og aphy; MRM, mul iple eac ion moni o ing; MS, mass
spec ome e ; MS/MS, andem mass spec ome y; PDA, pho odiode a ay de ec ion; SIM, selec ed ion moni o ing; 2D-LC, wo-dimensional liquid ch oma og aphy.
8 P. Dias e al.
h ps://doi.o g/10.1017/S0954422425100097 Published online by Camb idge Uni e si y P ess
py oline-5-ca boxyla e, a compound s uc u ally simila o
1-pipe ideine-6-ca boxylic acid, ha also leads o he
inac i a ion o PLP(337,338).
•Mu a ions in he PNPO gene in luencing PLP ecycling and
syn hesis(339–341).
•Mu a ions in he py idoxal phospha e-binding p o ein
(PLPBP) gene ( o me ly called p oline syn he ase co- an-
sc ibed homolog). PLPBP p o ec s PLP om damage by
in acellula phospha ases(342–345).
•Mu a ions in he ALPL gene encoding issue non-speci ic
alkaline phospha ase (TNSALP) in he me abolic diso de
hypophospha asia(346).
•Mu a ions in he PIGV,PIGO and PGAP2 genes esponsible
o he de elopmen o hype phospha asia wi h seizu es and
neu ologic de ici (Mab y synd ome). These genes play a
c ucial ole in he p oduc ion o he glycosylphospha idyli-
nosi ol ancho ha binds TNSALP o he cell memb ane.
Mu a ions esul in he p oduc ion o non- unc ional
glycosylphospha idylinosi ol ancho s and he subsequen
elease o TNSALP in o he blood(347).
These me abolic diseases associa ed wi h de ec s in i amin B
6
a e summa ised in Table 3.
Clinically used d ugs as an i i amins o B
6
In addi ion o na u al an i i amins o B
6
, he e a e also ce ain
clinically used d ugs ha ha e he same e ec . D ugs such as
heophylline (a b onchodila o used in he ea men o espi a o y
diseases, o example, as hma) and ca eine (psychos imulan )
di ec ly inhibi py idoxal kinase, he enzyme in ol ed in ac i a ion
o PLP. In he case o ca eine, such e ec s a e p obable solely in
in oxica ion. The esul is a PLP de iciency wi h accompanying
educ ion in PLP-dependen enzyme ac i i ies. Known conse-
quences include neu o oxic eac ions, o example, pe iphe al
neu opa hy, es lessness, agi a ion, emo s and seizu es(348–350).I
should be men ioned ha s anda dised ex ac s om Ginkgo
biloba a e easily a ailable and used in he he apy o a numbe o
condi ions, such as pe iphe al ci cula o y dis u bances, dizziness
and inni us, e c.(98,351,352). Hyd azine de i a i es, beyond he
a o emen ioned gy omi in, also include he an i ube culosis d ug
isoniazid (isonico inic acid hyd azide). Adminis a ion o his d ug,
pa icula ly in o e dose, esul s in no only he inhibi ion o
py idoxal kinase by he isoniazid me aboli e (hyd azone) bu also
he inac i a ion o PLP by o he isoniazid me aboli es (hyd azines
and hyd azides), ha o m, o example, isonico inilhyd azide, a
compound ha is easily exc e ed in he u ine(353).Ano he
an i ube culosis d ug, cyclose ine, eac s wi h PLP o ming co alen
complexes ha migh inhibi py idoxal kinase(354). Ano he g oup o
d ugs, including penicillamine and le odopa, o m complexes wi h
PLP, bu hey do no inhibi py idoxal kinase(355,356). In addi ion,
an iepilep ic d ugs (pheny oin, alp oic acid, and ca bamazepine)
inc ease he me abolism o i aminB
6
i ame s, esul ing in low PLP
plasma le els(357).
Die a y ecommenda ion and pha macological use o
i amin B
6
Vi amin B
6
is a ailable in bo h mul i i amin p epa a ions wi h
o he B i amins and as a single i amin p epa a ion. O al able s
o solu ions o pa en e al (in a enous, in amuscula ) admin-
is a ion a e he mos common o ms; hey usually con ain
py idoxine hyd ochlo ide o some imes PLP.
In adul s, he cu en ecommended die a y allowances ange
be ween 1·3–2·0 mg/d. Du ing p egnancy, lac a ion and in he
elde ly, his equi emen is inc eased(286). Recommenda ions o
py idoxine in ake acco ding o age and gende a e lis ed in Table 4.
As a supplemen , i amin B
6
is used especially in cases o i s
de iciency, which may be due o insu icien in ake o inc eased
need, as speci ied ea lie . As a medica ion, py idoxine o PLP a e
gi en p ophylac ically o he apeu ically o pa ien s wi h py idox-
ine-dependen epilepsy. In newbo ns wi h he edi a y synd ome, i
is necessa y o adminis e his i amin in he i s week o li e o
p e en men al e a da ion o anaemia, and li elong he apy is
necessa y. In he li e a u e, howe e , he e is a lack o cong uence
ega ding dose ecommenda ions. The op imal dosage should
Table 3. Inbo n me abolic diso de s ela ed o py idoxine dependen seizu es
Disease (synonyms)
Gene ic
de ec
O he symp oms excep
seizu es
An iqui in de iciency
(py idoxine-dependen
seizu es)
ALDH7A1 De elopmen al delay,
in ellec ual disabili y,
abdominal dis en ion
Hype p olinaemia II
(py oline ca boxyla e
dehyd ogenase de iciency)
ALDH4A1 De elopmen al delay, men al
e a da ion
PNPO de iciency
(py idoxamine5´-
phospha e oxidase
de iciency)
PNPO De elopmen al delay,
side oblas ic anaemia,
mic ocephaly, eeding
di icul ies
PLPBP de iciency PLPBP De elopmen al delay,
in ellec ual disabili y,
mic ocephaly, anaemia
Hypophospha asia ALPL Impai ed calci ica ion o
bones/ ee h, anaemia,
espi a o y insu iciency
Hype phospha asia
(Mab y synd ome)
PIGV,
PIGO,
PGAP2
Men al e a da ion,
in ellec ual disabili y, acial
dysmo phism,
b achy elephalangy, anal
s enosis
Table 4. Recommenda ions o i amin B
6
in ake by gende and age(286)
Indi iduals Condi ion, age Dose (mg/d)
Men 19–50 yea s 1·3
>51 yea s 1·7
Women 19–50 yea s 1·3
>51 yea s 1·5
p egnancy 1·9
lac a ion 2·0
Child en up o 6 mon hs 0·1
7–11 mon hs 0·3
1–3 yea s 0·5
4–8 yea s 0·6
9–13 yea s 1·0
Adolescen male 14–18 yea s 1·3
Adolescen emale 14–18 yea s 1·2
Biological p ope ies o i amins o he B-complex 9
h ps://doi.o g/10.1017/S0954422425100097 Published online by Camb idge Uni e si y P ess
inc eases panc ea ic glucokinase ac i i y in a panc ea ic isle
p ima y cul u es, and 100 nM bio in duplica ed he ac i i y
obse ed in con ols. Also, glucokinase mRNA le els inc eased by
~80% a e incuba ion wi h 1 μM bio in du ing 24 h(600). Mo eo e ,
a s udy using a hepa ocy es demons a ed ha he addi ion o
bio in (1 μM) o he cul u e medium induces a h ee old inc ease in
he con en o cGMP and a ou old inc ease in glucokinase ac i i y
and mRNA le els(601). Thus, bo h panc ea ic and hepa ic
glucokinase a e egula ed by bio in in a posi i e manne (600,601).
Rega ding he unde lying mechanisms in ol ed in gene
egula ion, bio inyl-AMP, which is he in e media y p oduc
o med by he ac ion o holoca boxylase syn he ase, is hough o
be esponsible o he gene egula o y unc ions o bio in. Bio inyl-
AMP ac i a es he soluble guanyla e cyclase wi h a subsequen
inc ease in in acellula concen a ions o cGMP and ac i a ion o
p o ein kinase G(602,603). This signal ansduc ion pa hway is
in ol ed in he egula ion o genes in ol ed in bio in homeos asis
and unc ion, including bio in-dependen ca boxylases and
holoca boxylase syn he ase, SMVT and o he s ( o example, he
asialoglycop o ein ecep o and oncogenes). Holoca boxylase
syn he ase mRNA le els in he li e , kidney, muscle and b ain
o a s ed a bio in-de icien die we e signi ican ly lowe compa ed
wi h he con ols. Con e sely, py u a e and p opionyl CoA
ca boxylase mRNA le els we e no al e ed, while he amoun s o
Fig. 5. Physiological unc ion o bio in. (a) Schema ic ep esen a ion o he bio in cycle. F ee bio in binds co alen ly o i e apoca boxylases: p opionyl-CoA ca boxylase (PCC),
me hylc o onyl-CoA ca boxylase (MCC), py u a e ca boxylase (PC) and ace yl-CoA ca boxylases (ACC-1 and ACC-2), by he ac ion o bio in holoca boxylase syn he ase. This s ep
equi es ATP and gi es ise o ac i e holoca boxylases, which a e impo an in amino acid ca abolism, he syn hesis and oxida ion o a y acids and gluconeogenesis. When
needed, holoca boxylases can be p o eolysed o biocy in. Then, bio inidase allows he elease o ee bio in. Adap ed om(378,586).(b) Simpli ied scheme o a human mi ochond ion
and bio in-dependen ca boxylases, hei ole and loca ion (cy osol, ou e memb ane and ma ix). ACC-1, ace yl–CoA ca boxylase 1; ACC-2, ace yl-CoA ca boxylase 2; PCC, p opionyl–
CoA ca boxylase; MCC, me hylc o onyl-CoA ca boxylase; PC, py u a e ca boxylase; aa, amino acids ( aline, isoleucine, me hionine, h eonine). Adap ed om(649).
16 P. Dias e al.
h ps://doi.o g/10.1017/S0954422425100097 Published online by Camb idge Uni e si y P ess

hese enzymes we e lowe .(604)Bio in was also iden i ied as he
ac o equi ed o he exp ession o he asialoglycop o ein
ecep o in he human li e cance cell line HepG2(605).
Mo eo e , in i o s udies demons a ed ha exp ession o
oncogenes (N-myc, c-myb, N- as and a ) co ela e posi i ely
wi h bio in concen a ions. A pha macological concen a ion o
bio in (10 nM) inc eased he exp ession o N-myc o 120%,
whe eas a e y low bio in concen a ion (25 pM) dec eased i o
53% compa ed wi h he con ols con aining bio in a a
physiological concen a ion (250 pM)(606). Mo eo e , some s udies
indica e ha bio in-dependen genes a e clus e ed in speci ic
ch omosomes(607).
Bio in as an i-in lamma o y and immunomodula o
Recen s udies also epo ed a link be ween bio in and immune and
in lamma o y unc ions. Mice no -abso bing bio in due o
knockou o he SMVT gene e ealed ch onic in lamma ion in
he cecum(608). Bio in-de icien human monocy e–de i ed den-
d i ic cells demons a ed a highe sec e ion o cy okines such as
umou nec osis ac o α(TNF-α), IL-12p40, IL-23 and IL-1β(609).
Bio inidase de iciency, an inbo n diso de cha ac e ised by
impai ed bio in bioa ailabili y and ecycling, can be associa ed
wi h weakened immuni y ha mani es s as ecu en in ec ions
and de ma i is(610). Indeed, bio in de iciencies a e o en associa ed
wi h skin mani es a ions(611). The unde lying pa hophysiological
mechanisms could be al e a ions in he ole o bio in-dependen
ca boxylases, such as ace yl–CoA ca boxylase 1 o p opionyl-CoA
ca boxylase, in e e ing wi h a y acid me abolism and he
cu aneous immune sys em. Mo eo e , immune and in lamma o y
unc ions o bio in canno be explained solely by i s in ol emen in
ca boxyla ion bu also ia i s e ec s on ansc ip ional ac o s such
as nuclea ac o κB and Sp1/3(599). Nuclea ac o κB egula es
genes in ol ed in in lamma ion and inna e and adap i e immune
esponse. Sp1 and Sp3 ha e been associa ed wi h he exp ession o
he gene encoding he cy okine IL-10(612).
Labo a o y assessmen o bio in s a us
Me hods o measu emen o bio in a e summa ised in Table 2
(mo e de ails a e shown in Supplemen a y Da a Table S2).
Indica o s o bio in s a us could be help ul in he diagnosis o
condi ions associa ed wi h bio in de iciency. S a on e al.
iden i ied lymphocy e p opionyl-CoA ca boxylase (PCC) ac i i y
as an indica o o bio in de iciency in human subjec s(613).
Howe e , due o analy ical issues, he PCC assay is no adequa e
o assess bio in s a us in la ge popula ion s udies. Ano he ma ke
is he plasma le el o 3-hyd oxyiso ale yl ca ni ine. This migh be
an ea ly and sensi i e indica o o bio in de iciency in humans(614).
Mo eo e , u ina y 3-hyd oxyiso ale yl ca ni ine could also be
used(615).
Bio in de iciency and ela ed diso de s
F ank bio in de iciency cases we e epo ed in people who
consume aw egg whi e o long pe iods, in cases o pa en e al
nu i ion, and inbo n e o s o me abolism ha cause bio in
was ing(379,616).
Nu i ional bio in de iciency and inhe i ed diso de s associa ed
wi h gene mu a ions encoding holoca boxylase syn he ase o
bio inidase gi e ise o a pa hological s a e called mul iple
ca boxylase de iciency. The pa hophysiological mechanisms
include: (1) in he case o holoca boxylase syn he ase de iciency,
a dec ease in he a ini y o holoca boxylase syn he ase o bio in
wi h consequen impai men in he o ma ion o holoca boxylases
a physiological bio in le els, and (2) in he case o bio inidase
de iciency, al e a ions in bio in elease om i s p o ein conjuga es
and hence i s ecycling (Fig. 5a). This is ollowed by i s loss in u ine
as biocy in. The es ima ed incidence o bio inidase de iciency
is ~ 1:60 000–80 000 o newbo ns, whe eas holoca boxylase
syn he ase de iciency is es ima ed o be less han 1:200 000 o
newbo ns. Bo h a e au osomal ecessi e diso de s. Clinical
mani es a ions o bio inidase de iciency include seizu es, hypo-
onia, lack o coo dina ed mo emen and balance impai men ,
espi a o y p oblems, hea ing and ision loss, skin ashes, hai loss
and e a ded cogni i e and physical de elopmen . Holoca boxylase
syn he ase de iciency symp oms include se e e me abolic acidosis,
le ha gy, hypo onia, omi ing, seizu es, hypo he mia, uncon-
sciousness, and e en coma and dea h. All hese clinical
mani es a ions om bo h diso de s espond well o ea ly ea men
h ough bio in supplemen a ion(617). The dose needed o he
ea men is no excessi e, and he onse o he e ec is ela i ely
apid. In a case epo o wo Chinese in an s wi h la e-onse
holoca boxylase syn he ase de iciency, 30 mg/d bio in ea men in
he ini ial phase sol ed he me abolic diso de s wi hin 48h.
Mo eo e , in he ollowing pe iod, bio in supplemen a ion
imp o ed he pa ien ’s clinical condi ion(618).
Bio in- hiamine- esponsi e basal ganglia disease is a a e
au osomal ecessi e neu ome abolic diso de . Fo me ly, i was
Table 7. Bio in-dependen ca boxylases, hei loca ion in cells and oles
Bio in-dependen
ca boxylases Loca ion Roles Re e ences
Ace yl-CoA
ca boxylase 1 (ACC-1)
Cy osol Ca boxyla ion o ace yl-CoA o malonyl-CoA. ACC-1 iso o m is exp essed in lipogenic issues
such as he li e and kidney
(686)
Ace yl-CoA
ca boxylase 2 (ACC-2)
Ou e
mi ochond ial
memb ane
Ca boxyla ion o ace yl-CoA o malonyl-CoA. ACC-2 iso o m is exp essed in skele al muscles
and he hea , issues whe e a y acid oxida ion is impo an
(686)
Me hylc o onyl-CoA
ca boxylase (MCC)
Mi ochond ial
ma ix
Ca abolism o leucine and ca boxyla ion o 3-me hylc o onyl-CoA o 3-me hylglu aconyl-
CoA
(687)
Py u a e ca boxylase
(PC)
Mi ochond ial
ma ix
Ca alysis o he ans o ma ion o py u a e o oxaloace a e (688)
P opionyl-CoA
ca boxylase (PCC)
Mi ochond ial
ma ix
Ca alysis o he con e sion o p opionyl-CoA o me hylmalonyl-CoA (689)
Biological p ope ies o i amins o he B-complex 17
h ps://doi.o g/10.1017/S0954422425100097 Published online by Camb idge Uni e si y P ess
called bio in- esponsi e basal ganglia disease and desc ibed as a
subacu e encephalopa hy, wi h con usion, dysa h ia and dyspha-
gia wi h occasional sup anuclea acial ne e palsy o ex e nal
oph halmoplegia ha can p og ess o se e e quad ipa esis and
e en dea h. Symp oms o bio in- hiamine- esponsi e basal ganglia
disease disappea wi hin a ew days wi h bio in ea men (5–10
mg/kg/d), and elapse occu s wi hin 1 mon h i bio in is
discon inued(619). Recen s udies ha e shown ha egimens o
cu ing his condi ion include bo h bio in and hiamine o ea and
p e en acu e c ises and elapses(620).
Recen clinical s udies ha e ocused on cases o ma ginal bio in
de iciency. Thei incidence is highe han was assumed in he
pas (615). Logically, he absence o symp oms commonly p esen in
bio in de iciency is no a sui able ma ke o i amin B
7
ma ginal
de iciency.
Bio in de iciency is e a ogenic in se e al animal species. In
mice, egg-induced bio in de iciency caused a highe incidence o
c anial mal o ma ions and sho ening o he long limb bones(621).I
need no be emphasised ha o he i amins o he B complex, such
as olic acid, ha e al eady been shown o be essen ial(622). Hence,
he oles and kine ics o bio in in p egnancy dese e a en ion. A
c oss-sec ional s udy o no mal human ges a ion epo ed an
inc eased exc e ion o 3-hyd oxyiso ale ic acid in ea ly and la e
p egnancy. Howe e , he e was a pa adoxical inc ease in bio in
exc e ion la e in p egnancy, sugges ing ha bio in s a us in
p egnancy was no educed(623).Con e sely, a longi udinal s udy
wi h women om ea ly o la e p egnancy ound e idence ha
bio in s a us dec eases du ing p egnancy. By la e p egnancy,
app oxima ely hal o he pa icipan s showed less han he lowe
limi o no mal bio in exc e ion a es(624).
Pha macological use o bio in
Pha macologic doses o bio in a e used o ea ing pa ien s wi h
diso de s o bio in me abolism as men ioned in he p e ious
chap e . Holoca boxylase syn he ase de iciency can be ea ed wi h
10 mg bio in/d wi h child en showing imp o emen in hei
condi ion, while bio inidase de iciency can be ea ed wi h a dose o
5–20 mg bio in daily(380).
Conside ing he po en ial neu op o ec i e ole o bio in, i s use
in he ea men o neu ological diseases could be bene icial. In an
open-label s udy wi h wen y- h ee pa ien s wi h p ima y and
seconda y p og essi e mul iple scle osis, ea men wi h high-dose
bio in (100–300 mg/d) om 2 o 36 mon hs e ealed an
imp o emen in se e al symp oms. O e all, he clinical imp o e-
men was delayed by 2–8 mon hs, and 300 mg bio in/d, a 10 000
imes highe dose han he ecommended daily in ake, gene a ed
he bes clinical esponse(625). Some mechanisms we e sugges ed o
be esponsible: (1) ac i a ion o py u a e ca boxylase, p opionyl–
CoA ca boxylase and me hylc o onyl-CoA ca boxylase may lead
o an inc ease in ATP p oduc ion in neu ons, and (2) ac i a ion o
ace yl–CoA ca boxylases may lead o myelin epai .(625)A double-
blind, placebo-con olled s udy wi h 154 pa ien s wi h p ima y o
seconda y p og essi e mul iple scle osis ecei ing 100 mg o bio in
o ally, h ice daily o placebo o 12 mon hs co obo a ed he
p e ious indings(626). In con as , in an obse a ional p ospec i e
s udy o 178 pa ien s, again wi h p ima y and seconda y
p og essi e mul iple scle osis, high-dose bio in did no show a
clea imp o emen in disabili y and quali y o li e(627).
Rega ding die a y bio in supplemen s, hey equen ly appea
as combina ions o he B-complex i amins o mul i i amin
complexes. I s main indica ions a e o o i y hai , nails and skin.
Al hough se e al epo s ha e demons a ed clinical imp o emen
a e bio in supplemen a ion in cases o bio in de iciency, esea ch
demons a ing i s e icacy in hai and nail g ow h in heal hy
indi iduals is limi ed(628).
Bio in is syn hesised de no o in plan s, ungi and mic oo gan-
isms, and his p ope y migh be used om a he apeu ic poin o
iew. Fo ins ance, Mycobac e ium ube culosis needs o bio-
syn hesise his i amin o i s pa hogenici y du ing all s ages o he
li e cycle. Fo his eason, inhibi o s o bio in biosyn he ic enzymes
could be a po en ial a ge o he de elopmen o no el an ibio ics
agains ube culosis(629).
Toxici y o bio in
Owing o being wa e soluble, excessi e amoun s o bio in a e
known o be easily exc e ed. Hence, i seems his i amin is
ela i ely non- oxic. Mo eo e , he maximum daily dose is unlikely
o cause ad e se side e ec s in he gene al popula ion, ha is, he
ole able uppe in ake le el, has no ye been es ablished(630,631).
Rega dless, he e a e some conce ns abou high-dose bio in. A
case epo o a 54-yea -old woman wi h p og essi e mul iple
scle osis epo ed an agg a a ion o he neu ologic s a e,
accompanied by lipid s o age in muscle, a e 5 mon hs o
ea men wi h h ee imes 100 mg bio in/d. Symp omsdisappea ed
in a ew mon hs a e bio in wi hd awal(632). In addi ion, animal
expe imen s wi h mice ed wi h a bio in-supplemen ed die (97·7
mg ee bio in/kg) o e 8 weeks e ealed al e a ions in he es is(633).
In addi ion, expe imen s wi h a s ed 5000 and 8000 mg bio in/kg
die s o 28 d showed a dec ease in es is weigh (634). These esul s
a e in disag eemen wi h in i o e ilisa ion s udies in which bio in
supplemen a ion o spe m wash medium (2·44 mg/ml) imp o ed
he e ilising abili y o mice spe ma ozoa(635).
In e e ences wi h es s
Ele a ed blood le els o bio in cause in e e ence in s ep a idin–
bio in ho mone immunoassays(636–638). In compe i i e assays ( o
example, iiodo hy onine, hy oxine, s e oid ho mones and 25-
hyd oxy i amin D), he e a e alsely inc eased ho mones concen-
a ions, whe eas in sandwich assays ( o example, glycop o ein
egula ing ho mones), alsely dec eased ho mones concen a ions
ha e been epo ed(639). The deg ee o in e e ence is dependen on
plasma bio in concen a ion, and i is signi ican a concen a ions
o 30 μg/L o mo e(637). False hype hy oidism is he mos
equen ly misdiagnosed endoc ine diso de (514,637,640–642).
Likewise, alse high 25–hyd oxy i amin D se um le els we e
de ec ed in pa ien s ecei ing high dose o bio in (>100 mg).
Logically, se e al conce ns a ise, since his is a c ucial labo a o y
es in mul iple scle osis pa ien s ecei ing i amin D supplemen-
a ion(637,643,644). Bio in in e e ence in ca diac oponin assays has
also been epo ed(645,646). Al hough, one analysis using a Roche
assay led o he conclusion ha his in e e ence is a e, and i s
p obabili y is e en lowe han o he con ounde s such as blood
sample hemolysis and simple biological a ia ion o ca diac
oponin(647). The In e na ional Fede a ion o Clinical Chemis y
Commi ee on Ca diac Bioma ke s (IFCC-CB) epo ed a ca diac
oponin assay in e e ence able o hemolysis and bio in o guide
heal hca e p o essionals and clinicians whene e he e is an
inconsis ency be ween ca diac bioma ke esul s and he clinical
si ua ion(645).
Bio in supplemen a ion has also been linked o al e a ions in
hepa i is B- i us (HBV), hepa i is C- i us (HCV) and human
immunode iciency i us (HIV)- ela ed se ological ma ke s(648).A
18 P. Dias e al.
h ps://doi.o g/10.1017/S0954422425100097 Published online by Camb idge Uni e si y P ess
s udy in which en heal hy olun ee s accina ed agains hepa i is
B we e adminis e ed a single o al dose o bio in (100 mg) e ealed
an i-HB le els below he cu o alue o ou o he en
pa icipan s. Mo eo e , a ound 80–90% o alse posi i e esul s
o an i-HBe and an i-HBc occu ed. On he con a y, in HIV and
HCV se ology es ing, bio in caused alse nega i e esul s(648).
Conclusions
The cu en e iew summa ised he li e a u e on wo B-g oup
i amins, B
6
and B
7
(also known as H o bio in). His o ically,
esea ch in e es in hese wo wa e -soluble i amins commenced
a he beginning o he wen ie h cen u y and allowed o he
iden i ica ion o nume ous cha ac e is ics and essen ial oles in
mul iple physiological unc ions ( o example, neu ological and
me abolic p ocesses). No el disco e ies, howe e , e ealed hei
much la ge physiological oles beyond hei pa icipa ion in
mul iple enzyma ic eac ions. Humans lack biosyn he ic pa hways
o i amins B
6
and B
7
and, he e o e, mus ob ain hem om
exogenous sou ces ( o example, oods and supplemen s). These
i amins a e also syn hesised by mic obio a in he human la ge
in es ine, and i is likely ha a pa o such p oduced i amins, a
leas in he case o bio in, can be abso bed and used by humans.
Cases o de iciency o i amins B
6
and B
7
a e a e. Howe e ,
inhe i ed diso de s associa ed wi h gene mu a ions equi e p omp
and li elong ea men wi h hese i amins, s a ing a ea ly li e
s ages ( ha is, in newbo ns). Mo eo e , i amin B
6
de iciency can
ollow adminis a ion o se e al clinically used d ugs ( o example,
isoniazid) o poisoning wi h Gy omi a mush oom and Ginkgo
biloba seeds. Beyond cases o de iciency, bo h i amins ha e been
used o es ed in se e al o he condi ions. Fo ins ance, py idoxine
has been used o p e en ion o omi ing in p egnancy, while
bio in has been ecen ly es ed in con olled ials o pa ien s wi h
p ima y and seconda y p og essi e mul iple scle osis. Las bu no
leas , bo h i amins a e conside ed ela i ely non- oxic when an
adequa e in ake is ollowed.
Recen esea ch has b ough no el disco e ies linking bo h
i amin B
6
and bio in wi h an i-in lamma o y e ec s in pa icula .
Howe e he apeu ic use o bo h i amins in a ious in lamma o y
diso de s s ill needs much mo e esea ch. In he case o bio in,
u he in es iga ion o i s ole in gene exp ession egula ion
h ough bo h ansc ip ion ac o s and epigene ic p ocesses is
necessa y.
Supplemen a y ma e ial. To iew supplemen a y ma e ial o his a icle,
please isi h ps://doi.o g/10.1017/S0954422425100097
Acknowledgmen s. We hank Albe o Gomes o his help in o ma ing he
igu es.
Au ho ship. P.D. w o e he biological sec ion on bio in. T.S. was esponsible o
sou ces o bo h i amins. M.V. w o e he biological sec ion on i amin B
6
. M.M.
and J.P. con ibu ed o c i ical assessmen o he pape . N.P., L.K.K. and L.K.
p epa ed and c i ically assessed chemical and analy ical issues. P.M. was
esponsible o concep ualisa ion, c i ical e iew, inalisa ion and ob ained
unding o he open access publica ion. All au ho s pa icipa ed in he c i ical
e ision o he a icle.
Financial suppo . This open-access e iew pape was suppo ed by he
p ojec New Technologies o T ansla ional Resea ch in Pha maceu ical
Sciences (NETPHARM), p ojec ID CZ.02.01.01/00/22_008/0004607, and is
co- unded by he Eu opean Union, and he E asmusþP og amme o he
Eu opean Union, Key Ac ion 2: S a egic Pa ne ships, P ojec no. 2020-1-
CZ01-KA203-078218.M.M. sends hanks o Cha les Uni e si y (SVV 260 663).
L.J., K.M. and L.K.K. send hanks o MH-CZ-DRO (UHHK, 00179906).
Compe ing in e es s. The au ho s ha e no ele an in e es s o decla e.
E hical s anda ds. No applicable.
Consen o Publica ion. No applicable.
A ailabili y o da a and ma e ials. The ollowing suppo ing in o ma ion is
a ailable h ough he online e sion o his a icle a he publishe ’s websi e.
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