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Vitamin B 6. Grace Coughlan Dawn Dunphy Kaitlyn McDonald Carla van den Berg. Overview. Introduction to Vitamin B 6 Absorption , Transport, Metabolism, Storage, Excretion Deficiency Static and Functional Tests Gold Standard Setting the EAR Setting the UL

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Vitamin B 6


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vitamin b 6

Vitamin B6

Grace Coughlan

Dawn Dunphy

Kaitlyn McDonald

Carla van den Berg

overview
Overview

Introduction to Vitamin B6

Absorption, Transport, Metabolism, Storage, Excretion

Deficiency

Static and Functional Tests

Gold Standard

Setting the EAR

Setting the UL

Necessary Improvements in Biochemical Assessment & Future Research Recommendations

functions of vitamin b 6
Functions of Vitamin B6

Vitamin B6 plays an important role in the metabolism of amino acids, glycogen and sphingoid bases.

Serves as a coenzyme for over 100 enzymes involved in the metabolism of proteins.

And because of its role in protein metabolism it plays an important role in the synthesis of heme.

functions continued
Functions Continued

Amino acids involved in the production of the neurotransmitters serotonin, dopamine, norepinephrine, histamine, taurine and Y-aminobutyric acid are dependent on PLP.

PLP is the coenzyme for the reaction that converts tryptophan to niacin.

Some studies suggest that vitamin B6 may also play a role in hormonal and cell mediated immune response. (Gibson)

variations
Variations
  • Pyridoxine (PN) and Pyridoxine 5’-phosphate (PNP)
  • Pyridoxamine (PM) and Pyridoxamine 5’-phosphate (PMP)
  • Pyridoxal (PL) and Pyridoxal 5’-phosphate (PLP)
bioavailability
Bioavailability

B6 is about 75% bioavailable in a mixed diet.

A mixed diet is typically about 15% PN.

food sources
Food Sources

Non-Citrus Fruits

White Potatoes

Fish

Poultry

Meat

Seeds

Bran

Fortified Ready-To-Eat Cereals

absorption transportation
Absorption & Transportation

Absorption of Vitamin B6 occurs in the gut through phosphatase-mediated hydrolysis.

Here the nonphosphorylated form into the mucosal cells.

The B6 is then transported through nonsaturable passive diffusion into the blood stream.

metabolism
Metabolism

The absorbed nonphosphorylated B6 (PN, PL, PM) moves to the liver.

Here the phosphate group is added back on to these compounds by reacting with PL kinase.

PNP and PMP are then oxidized into PLP.

A reverse reaction can occur and transform PLP into PMP.

metabolism continued
Metabolism Continued

The PLP then becomes bound to proteins within tissues.

The binding capacity of these proteins prevent accumulation.

When the capacity is reached the liver hydrolyzes PLP and releases it into circulation as its nonphosphorylated form.

storage
Storage
  • The body’s vitamin B6 stores exist in a two-compartment model.
    • Muscle Stores and Muscle Pool
excretion
Excretion
  • Most of the hydrolyzed vitamin B6 is released by the liver and excreted in urine.
    • 4-pyridoxic acid (4-PA)
plasma plp the gold standard
Plasma PLP: The Gold Standard
  • The major transport form of vitamin B6 in the bloodGibson
    • Bound to protein or freeIOM
  • The major form of vitamin B6 in tissuesIOM
  • The active coenzyme speciesIOM

Pyridoxal-5’-phosphate

vitamin b 6 indicators
Vitamin B6 Indicators:

Direct, indirect & functional

Use multiple indicators to evaluate B6 status

Many tests are conducted to monitor status

1 erythrocyte aminotransferase
1) Erythrocyte aminotransferase

Two enzymes dependent on pyridoxal phosphate as coenzyme : alanine aminotransferase (A1AT) & aspartate aminotransferase (ASAT)

Transfer of an amino acid to create L- glutamate

In B6 deficiency, enzyme activity falls

Measuring of enzyme activity in erythrocytes measures vitamin B6 status

2 tryptophan catabolites
2) Tryptophancatabolites

One of the earliest markers of vitamin B6

Measuring the excretion of xanthurenic acid

Catabolites follow a pathway which is PLP enzyme dependent

When deficient, there is an increase in the excretion of xanthurenic acid

It is not known what level of excretion represents vitamin B6 deficiency

3 methionine
3) Methionine

Cystathinonine is dependent on B6 to break it down

When vitamin B6 is inadequate, there is an increase in cystathinonine excretion because it cannot be broken down in the body

The end product of cystathinonine break down is taurine, thus there will also be a decrease in taurine excretion.

A level of >350 umol/day of cystathinonine means means vitamin B6 is inadequate

plasma plp the gold standard1
Plasma PLP: The Gold Standard

Several studies done from 1975-1986 suggested that:IOM

~ ½ of the population have

plasma PLP [ ] < 30 nmol/L,

but do not show vitamin B6 deficiency

plasma plp the gold standard2
Plasma PLP: The Gold Standard

Lui et al., 1985 proposed:IOM

20 nmol/L = Plasma PLP cutoff

(No health risks)

plasma plp the gold standard3
Plasma PLP: The Gold Standard

> 0.05 mg

Abnormal encephalogram patterns

Plasma PLP [ ] = ~ 9 nmol/L

Suboptimal plasma PLP [ ] = 10 nmol/L

(Kretsch et al., 1991) IOM

plasma plp the gold standard4
Plasma PLP: The Gold Standard

Leklem, 1990:IOM

Plasma PLP [ ] of 30 nmol/L = lower end of normal status

plasma plp the gold standard5
Plasma PLP: The Gold Standard

The Plasma PLP cutoff is therefore:IOM

20 nmol/L

setting the ear men
Setting the EAR: Men

Protein interferes with vitamin B6IOM

Tryptophan metabolite excretion

setting the ear men1
Setting the EAR: Men

Baker et al. (1964)IOM

=30 g/day

= 10 g challenge dose

EAR < 1.25 mg PN

= 1.25 mg

setting the ear men2
Setting the Ear: Men

Yess et al. (1964)IOM

= 100 g/day

EAR < 0.9 mg PN

= 2 g load

= 0.6 g

OR

=0.9 g

= 0.16 mg

setting the ear men3
Setting the EAR: Men

Miller & Linkswiler (1967)IOM

= 54 g/day

OR

= 150 g/day

= 0.6 mg

= 0.16 mg

EAR < 0.76 mg PN

= slow excretion over 40 days

setting the ear men4
Setting the EAR: Men

Linkswiler (1978) IOM

= 100 g/day

= 1.0-1.6 mg PN

EAR < 1.0-1.5 mg PN

setting the ear men5
Setting the EAR: Men

Miller et al (1985) IOM

= 1.6 mg

> 30 nmol/L

= 0.5 g/kg

OR

=1.0 g/kg

OR

=2.0 g/kg

1.5 mg > EAR

setting the ear men6
Setting the EAR: Men

Selhub et al. (1993) IOM

= 1.3 mg

Similar homocysteine [ ]

EAR < 1.3 mg

setting the ear men7
Setting the EAR: Men

Overall Range: < 0.9 mg  < 1.9 mg

EAR for Men = 1.1 mg/dayIOM

setting the ear women
Setting the EAR: Women

Majority used plasma PLP [ ] as indicatorIOM

setting the ear women1
Setting the EAR: Women

Brown et al (1975)IOM

Depletion

Repletion

= 78 g/day

=1.0 mg

OR

=2.2 mg

EAR just under 1.0 mg

= 0.16 mg

 to 24 and 60 nmol/L

 5040 nmol/L

setting the ear women2
Setting the EAR: Women

Driskell et al (1989)IOM

B6 status of 15 obese women

=60 nmol/L in obese

Obesity does not affect vitamin B6 status

=1.18 mg

=63 nmol/L in non-obese

EAR < 1.2 mg

setting the ear women3
Setting the EAR: Women

Kretsch et al. (1995)IOM

Baseline values (25 nmol/L) developed from

= 1.55 g/kg

= 2 mg PN

Depletion

Repletion

EAR= 1.0 mg

=0.5 mg OR =1.0 mg

OR =1.5 mg

OR =2.0 mg

< 0.05 mg

Baseline < 10 nmol/L

=Restored from 1.0-1.5 mg

setting the ear women4
Setting the EAR: Women

Hansen et al. (1996)IOM

Looked at effect of protein intake on vitamin B6

=0.5 g/kg

OR

=1.0 g/kg

OR

=2.0 g/kg

> 30 nmol/L

EAR considerably < 1.25 mg

=20-30 nmol/L

=1.25 mg PN diet

Assuming PLP [ ] cutoff= 20 nmol/L…

setting the ear women5
Setting the EAR: Women

Hansen et al. (1996)IOM

Looked at effects on status indicators from diets with low or high glucoside PN

EAR < 1.5 mg

  • Indicators suggested lower bioavailability of glucoside

= 9% B6 glucoside

OR

=27% B6 glucoside

> 30 nmol/L

setting the ear women6
Setting the EAR: Women

Hansen et al. (1997)IOM

= 85 g/day

Baseline

=1.03 mg

OR

=0.84 mg

EAR < 0.8 mg

Repletion

  • 3-4 different levels for 10-12 day periods
setting the ear women7
Setting the EAR: Women
  • Huang et al. (1998)IOM

= 1.55 g/kg

Baseline

= 1.6 mg/day

Repletion

EAR between 0.45-1.26 mg; most likely < 1mg

=1.26 mg for 21 days

=1.66 mg for 21 days

=2.06 mg for 14 days

Depletion

= 0.45 mg/day

Normalized with 1.5-2.0 mg PN

ul toxicity
UL & Toxicity
  • Vitamin B6 from food≠ toxicityIOM
  • Due to supplementation
  • UL = 100 mg
    • Different for children and adolescents diet.ssuppl.factsheet
  • High pyridoxine levelsMK
ul toxicity m k
UL & Toxicity M&K

Akinesia

Loss of balance and reflexes

Altered peripheral sensation

Absence of sensory nerve action potentials

Convulsions

ul toxicity1
UL & Toxicity

Taking excess vitamin B6 during pregnancy can cause adverse effects for the infantM&K

Large doses during pregnancy should be avoidedM&K