Vitamin B-6 deficiency may prove to be one of the most common types of nutrient deficiencies. While this may sound surprising to some people, there are actually several possible causes why someone would be deficient in Vitamin B-6. Additionally, Vitamin B-6 (in its active form in the body known as pyridoxal-5-phosphate or P5P) is a nutrient that participates in at least 100 essential biochemical processes in the body.
Deficiencies of Vitamin B-6 can actually cause a compendium of different types of symptoms. These symptoms can point to problems with: mood, behavior, detoxification, methylation, intestinal functions, seizures, hormonal balance, fatty acid metabolism, skin and connective tissue, red blood cell formation, brain and cognition and liver function.
Essential Roles Of Vitamin B-6
The proper term referring to B-6 for its chemical reactions in the body is “P5P”, pyridoxal-5-phosphate. Therefore, P5P is used below when referring to Vitamin B-6.
Because of its involvement in so many physiological systems, listing every function of B-6 is not possible in a simple article. However, we can glean some of the most important functions of B-6, as well as learn the conditions that can arise from P5P deficiency.
- Amino Acid Metabolism – There are more than 60 amino acid-based enzyme reactions that involve P5P as a cofactor. Amino acids are the building blocks of DNA/RNA, numerous biochemical processes, and liver detoxification. One such reaction involves the synthesis of the amino acid taurine from cysteine, via a P5P dependent enzyme. The synthesis of the sulfur amino acid cysteine is dependent upon P5P as a co-factor (1).
- Neurotransmitter Synthesis – 3 key amino acids are synthesized with P5P as a co-factor: GABA, Serotonin and Dopamine. The inhibitory brain neurotransmitter GABA is made from Glutamate via a P5P-dependent reaction. This key reaction may be a main reason why people with anxiety disorders benefit from B-6/P5P supplementation. Another key function of P5P is in the conversion of 5-HTP into serotonin. Deficiency of B-6 or P5P can directly reduce the amount of serotonin that is synthesized. Additionally, the synthesis of Dopamine from L-DOPA is dependent upon a P5P reaction (1,2).
- Iron metabolism – A deficiency of vitamin B-6 can cause a deficiency of hemoglobin, leading to microcytic anemia. Most clinicians think that when red blood cells are microcytic, it is caused by iron deficiency. While this may be correct in some cases, P5P deficiency can also cause microcytic anemia. P5P is a co-factor in the synthesis of aminolevulinate, which is the first step in heme biosynthesis. (1, 2)
- Detoxification Processes – P5P is the co-factor in the synthesis of cystathionine via the enzyme CBS (cystathionine beta synthase). This is the first step in the synthesis of the amino acid cysteine, a sulfur-containing amino acid that plays a very important role as a component of 2 critical antioxidants: glutathione and metallothionein. Both of these cellular antioxidants feature cysteine as its sulfur-amino acid. Without sufficient amounts of glutathione or metallothionein, there is a severe increase in free radicals and various toxins, chemicals and heavy metals.
- Seizure Disorders – B-6/P5P deficiency can cause certain types of seizures. A number of the decarboxylases for neurotransmitter synthesis are P5P-dependent. Another possible scenario of convulsions and certain seizures involves high levels of various tryptophan metabolites. The accumulation of these metabolites can occur due to a deficiency of B-6/P5P. Remember that P5P is involved in converting 5-HTP into serotonin. Tryptophan is the precursor of 5-HTP. Another type of seizure is known as “pyridoxine dependent epilepsy”. This is caused by a gene mutation in ALDH7A1. Individuals with this condition require massive doses of P5P for regular maintenance (2,3).
- Methylation & Synthesis of Folate Metabolites – Tetrahydrofolate (THF) is an important form of folate that is needed for DNA and RNA synthesis. Formation of THF is dependent upon P5P as a co-factor.
- Hyperhomocysteinemia – Homocysteine levels, when elevated are a known independent risk factor cardiovascular diseases. Elevated levels of homocysteine have been known to increase blood platelet aggregation, as well as increase certain inflammatory proteins such as TNF-a and MMP9. P5P plays a crucial role by converting homocysteine into cystathionine, via the enzyme CBS within the transsulfuration pathway.
Causes of B-6 Deficiency
There can be numerous causes of Vitamin B-6/P5P deficiency. It is also important to point out that some individuals can have a significantly increased need for Vitamin B-6, due to various genetic, and environmental factors. The following is a summation of the key factors that can cause a deficiency of Vitamin B-6.
- Contraceptives (birth control medications) – Cohort studies have found that the use of oral contraceptives are associated with B-6 deficiency (4)
- Hydralazine – This class of anti-hypertensive drugs is known to deplete P5P (5)
- Hydrazide – This herbacide often found in cigarettes depletes P5P
- Tartrazine – This chemical known as “yellow No. 5” is often added to processed foods and soda pop
- Pyrrole Disorder – This condition causes a depletion of certain aldehydes such as B-6. Elevated pyrroles tend to be produced because of genetic susceptibilities, and may also be produced when there is increased oxidative stress or chronic infections (6)
- Inflammation and the cell danger response (CDR) are associated with shifts in Vitamin B-6 metabolism, and deficiency states (9, 10). This is due in large part to the transport of Vitamin B-6 towards sites of inflammation and through the activation of the kynurenine pathway, leading to the degradation of the amino acid tryptophan (10).
Testing For B-6 Deficiency & Symptoms of B-6 Deficiency
On a routine blood test, the most related markers are decreases in the ALT (alanine aminotrasferase) and AST (asparatate amino transferase) enzymes. Both of these metabolic enzymes are B-6-dependent. Values less than 12 are good indicators of B-6 deficiency.
On a urinary organic acids test, elevations in the xanthurenate or kynurenate markers are a good indicator of B-6 deficiency.
Low levels of plasma PLP <30 nmol/l are a good indicator of B-6 deficiency.
Symptoms of B-6 deficiency may include: anxiety, seizures, involuntary jerking movements or tics, neuropathy, iron-deficiency that does not correct with iron-rich foods or iron supplementation, elevations in homocysteine.
A valid, indirect method of assessing B-6 deficiency are elevations of urinary hydroxyhemopyrrolin, 2,1 aka urinary pyrroles or pyroluria (11). Pyrrole disorder aka pyroluria is a type of porphyrin disorder of heme metabolism, whereby elevated hydroxyhemopyrrolin, 2,1 leads to an irreversible binding to B-6 and zinc causing deficiency. Pyrrole disorder has been long recognized as a significant factor in mental illness and behavior disorders (11).