From the Guidelines
Diagnosing functional vitamin B6 deficiency requires a comprehensive approach that includes measuring serum pyridoxal 5'-phosphate (PLP) levels and performing functional tests such as the tryptophan load test or the assessment of xanthurenic acid excretion in urine after tryptophan loading, as recommended by the most recent guidelines 1. To diagnose functional vitamin B6 deficiency, it is essential to look beyond standard B6 blood levels. The most reliable approach involves:
- Measuring serum pyridoxal 5'-phosphate (PLP, the active form of B6) to assess the body's B6 status
- Performing functional testing such as the tryptophan load test or the assessment of xanthurenic acid excretion in urine after tryptophan loading to evaluate how effectively the body is utilizing B6
- Measuring erythrocyte transaminase activity with and without PLP stimulation (EGOT test) to reveal functional deficiency even when blood levels appear normal Symptoms that might suggest functional B6 deficiency include:
- Peripheral neuropathy
- Dermatitis
- Glossitis
- Depression
- Confusion
- Microcytic anemia Risk factors for functional B6 deficiency include:
- Certain medications (isoniazid, hydralazine, penicillamine)
- Alcoholism
- Kidney disease
- Autoimmune disorders
- Genetic variations affecting B6 metabolism According to the ESPEN micronutrient guideline 1, the recommended daily intake of vitamin B6 is 1.3-1.7 mg/day for adults, and the upper limit for pyridoxine is 100 mg/day for adults. However, the guideline also notes that there are no stores of pyridoxine, and diet is the only source of vitamers, emphasizing the importance of adequate dietary intake or supplementation when necessary. The potential toxicity of high doses of pyridoxine, as reported in the guideline 1, highlights the need for careful consideration of supplementation doses to avoid adverse effects.
From the Research
Diagnosing Functional B6 Deficiency
To diagnose functional B6 deficiency, several factors and methods can be considered:
- Plasma pyridoxal 5'-phosphate (PLP) levels: PLP is the principal circulating form of vitamin B6, and its levels can indicate B6 deficiency 2. However, elevated PLP levels do not always rule out B6 deficiency, as seen in cases of hypophosphatasia (HPP) where PLP accumulates extracellularly 2.
- 4-Pyridoxic acid (PA) levels: PA is a B6 degradation product, and low plasma levels can confirm B6 deficiency 2.
- Dietary history and breast milk pyridoxal (PL) levels: These can indicate B6 deficiency in individuals, particularly in breast-fed newborns and their mothers 2.
- High-performance liquid chromatography (HPLC) method: This method can be used to determine plasma PLP concentrations, which can indicate vitamin B6 adequacy 3.
- Cut-off values for plasma PLP: Current cut-off values for plasma PLP may not accurately reflect vitamin B6 deficiency, and a significant percentage of individuals may be at risk of deficiency despite having adequate vitamin B6 intakes 3.
Biochemical Markers and Pathways
Vitamin B6 plays a crucial role in various biochemical pathways, including:
- Amino acid and homocysteine metabolism
- Glucose and lipid metabolism
- Neurotransmitter production and DNA/RNA synthesis
- Cellular signaling and antioxidant functions 4, 5
- Transsulfuration pathway: Vitamin B6 deficiency can affect the function of this pathway, leading to increased cystathionine concentrations and altered hydrogen sulfide production 6
Considerations for Diagnosis
When diagnosing functional B6 deficiency, it is essential to consider:
- Subclinical, undiagnosed deficiency may be present in some individuals, particularly in the elderly 5
- Suboptimal vitamin B6 status may be associated with certain diseases, such as impaired cognitive function, Alzheimer's disease, cardiovascular disease, and cancer 5
- Wide individual variation in responses to vitamin B6 restriction or supplementation may affect the accuracy of diagnostic methods 6