Vitamin B6 is a generic term that refers to the group of pyridine-based compounds, including Pyridoxine, Pyridoxamine, Pyridoxal, and their phosphorylated derivatives, such as Pyridoxal-5-Phosphate (P5P), the form preferred by RN Labs. Pyridoxine is the most common form of this vitamin in over-the-counter dietary supplements, fortified foods, and beverages such as energy drinks.
- Pyridoxine needs to be converted into Pyridoxal-Phosphate via several steps, with phosphorylation by Pyridoxal Kinase to Pyridoxal-Phosphate being the most critical. This process can be impaired due to genetic or metabolic issues. At high doses, Pyridoxine can even saturate the enzymes responsible for this conversion, causing an accumulation of inactive Pyridoxine and disrupting normal enzyme functions, potentially leading to neuropathy.
- Pyridoxal-5-phosphate (P5P), the bioactive form of Vitamin B6 does not require conversion. It is readily utilised by the body, and excess amounts are easily excreted via normal metabolic pathways. This makes P5P a safer option, particularly for individuals with difficulty converting Pyridoxine into its active form.
Notably, Pyridoxine appears to compete with P5P for enzyme binding, inhibiting Pyridoxal-phosphate-dependent enzymes that are critical for neuronal function. This can contribute to neuronal cell death and neuropathy. In this way, excess Pyridoxine may in fact exacerbate P5P deficiency in certain situations, which has been suggested to explain why Vitamin B6 deficiency and toxicity often have overlapping symptoms.
Pre-converted vitamins are often described as ‘bioactive’ or ‘activated’ to denote their increased ability to be more readily used by the body after consumption (without substantial further conversion being required) and therefore more closely emulate the natural form of that vitamin as it is used by the body. Less activated forms are usually chosen for their affordability and stability, in order to maximise product returns. However, in many instances these forms may not necessarily exert the same metabolic effects as activated forms, making activated versions preferable in most cases where a premium quality product or potency is required.
Certain genetic differences between individuals can alter the needs and effects of Vitamin B6. For example Cystathionine-Beta-Synthase (CBS) is a key Vitamin B6 dependent enzyme that facilitates the production of Cysteine and lowering Homocysteine levels. Supplemental Vitamin B6 may upregulate this process when insufficient, as well as when already excessive. When an individual possesses certain less common genetic SNPs in this area, it is possible for Vitamin B6 to go underutilised. This can result in a counterintuitive situation where Vitamin B6 levels accumulate, even though the body is technically in a state of deficiency.
- Neurotransmitter synthesis, e.g. Serotonin, Dopamine, GABA, etc.
- Supporting healthy mood, especially in relation to premenstrual syndrome (PMS)
- Lipid metabolism (including cholesterol)
- Phase II detoxification
- Red blood cell formation and oxygen capacity
P5P has been suggested to support those experiencing neuropathy, including neuropathy caused by overload or toxicity of Pyridoxine. The mechanisms proposed for this include ensuring that adequate B6 activity can be maintained within neuronal systems, especially in situations where this activity may be obstructed by excess Pyridoxine.
The Recommended Daily Intake (RDI) for Vitamin B6 is relatively low (~1.5 mg) compared with doses commonly found in supplements, which can be a source of confusion. RDI levels are typically established based on large cohort population data for maintaining public health (by averting the symptoms and diseases of frank deficiency in the average population). Dosing regimens to support therapeutic outcomes often require higher doses than that of RDIs to fulfill specific individual needs, which highlights the importance of evaluating personal needs, circumstances and caution around self-prescribing and risks of overlapping polypharmacy when taking numerous supplements at the same time.
| Pyridoxal-5-Phosphate | 50 mg |
| Equiv. to Pyridoxine | 34.2 mg |
Conclusions
Vitamin B6 is an essential cofactor for maintaining healthy body function. While basic levels can be consumed via a rich and varied diet, certain individuals may have needs for higher amounts, in which case supplementation becomes necessary and/or advantageous.
The preactivated form Pyridoxal-5-Phosphate is not associated with the same complications as the conventionalunconverted form Pyridoxine, and it may therefore be preferable to use the activatedform when supplementing, especially with individuals who require higher clinical doses,and/or have difficulties metabolising Vitamin B6, including due to genetic variations.
References
Nutrient Reference Values
Click here to view Nutrient Reference Values for Australia and New Zealand
