B6 deficiency symptoms

What is B6 deficiency, and how common is it?

The NIH reports that isolated B6 deficiency is not common and that inadequate B6 status is usually seen together with low levels of other B vitamins such as B12 and folic acid. Symptoms of deficiency become more pronounced as levels fall; in people with borderline or mild deficiency, there may be no findings for months or even years. ^[1] EFSA also states that the most typical findings, although rare, are hypochromic microcytic anemia and neurological abnormalities. ^[2]

Low PLP and clinical deficiency are not the same thing. In cross-sectional studies relayed by EFSA, plasma PLP was below 20 nmol/L in 16–24% of adults aged 50 and over; in adults under 50 and in adolescents this proportion was found to be 0.5–5%. With age, in people not taking supplements, PLP falls by about 4 nmol/L per decade. ^[2]

Intake in Türkiye

In the analysis of TÜBER (Türkiye Dietary Guidelines) 2022 based on TBSA 2017 data, 69.2% of individuals aged 15 and over were below the average requirement (EAR) for B6 intake; in those aged 75 and over, the proportion was found to be 82.6% in men and 84.7% in women, and TÜBER states that the frequency of inadequate intake in this age group is much higher than in other age groups. These data are an intake distribution based on a dietary survey; they are not a measurement of blood PLP level and cannot be interpreted as the frequency of deficiency. ^[5]

What are the symptoms of B6 deficiency?

Because the NIH reports that B6 deficiency is seen together with low levels of other B vitamins such as B12 and folic acid, which finding in the table is due to which vitamin cannot be separated by symptoms; a symptom alone does not establish a diagnosis of B6 deficiency. ^[1]

Who is at risk of B6 deficiency?

According to the NIH, plasma PLP levels tend to be low in people with alcohol dependence, in people with obesity, in pregnant women (especially with preeclampsia or eclampsia) and in malabsorption disorders such as celiac disease, Crohn’s disease and ulcerative colitis. The NIH also counts people with impaired kidney function (end-stage kidney disease, chronic kidney failure; those on regular dialysis and kidney transplant recipients) and people with autoimmune disease (e.g., rheumatoid arthritis) among the groups at highest risk of inadequacy. ^[1]

EFSA relays that PLP was reported to be significantly lower in smokers than in non-smokers, even at similar B6 intake. For alcohol the result is not one-directional: in a study where consumption averaged 19 g (men) and 3 g (women) per day, alcohol was associated with higher PLP independent of B6 intake; on the other hand, the frequency of PLP below 20 nmol/L was high in chronic alcoholics with low B6 intake. ^[2]

Medications are also important. The isoniazid label states that pyridoxine deficiency is sometimes seen in adults at high doses and attributes this to isoniazid competing with pyridoxal phosphate; pyridoxine deficiency also appears in the adverse reactions section of the label. The NIH’s drug interaction section also mentions cycloserine and some antiepileptics, including valproic acid. ^{[6] [1]}

Vitamin B6 test: what should plasma PLP be?

The most common measurement in assessing deficiency is plasma PLP in blood. The NIH reports that B6 status can also be assessed by indirect routes such as erythrocyte aminotransferase saturation or tryptophan metabolites, but that plasma PLP is the most common measurement. EFSA also considers plasma PLP, despite some limitations, the most suitable indicator for deriving DRVs because it is the only biomarker reflecting tissue stores. ^{[1] [2]}

Thresholds differ by organization and not all answer the same question:

• NIH: reports that a PLP above 30 nmol/L is traditionally considered an indicator of adequate B6 status in adults, and that the FNB largely used the 20 nmol/L level as the criterion when calculating adult RDAs. The NIH also reports that in the US, plasma PLP was below 20 nmol/L in 11% of B6 supplement users and in 24% of those not using B6-containing supplements. ^[1]
• EFSA: accepts 30 nmol/L, as a population average, as an indicator of adequate B6 status and sets average requirements by this criterion. This is not defined as an individual diagnostic threshold. ^[2]

Laboratory reports may differ in units (nmol/L, µg/L or ng/mL); the EFSA 2016 document uses a molecular weight of 247.14 g/mol for PLP when converting ng/mL values to nmol/L, that is, 1 ng/mL is about 4.05 nmol/L. Accordingly, 20 nmol/L is about 5 ng/mL and 30 nmol/L is about 7.4 ng/mL (calculated). The result is interpreted together with the laboratory’s own reference range, the method used and the person’s condition. EFSA relays that plasma PLP falls with age, is found low in smokers, and rises 10–35% during intense running or cycling, then falls and urinary loss of B6 derivatives increases; that is, a single PLP value does not reflect a person’s long-term B6 status with the same reliability under all conditions. EFSA also states that the tryptophan loading test is not reliable in pregnant women and in oral contraceptive users because of estrogen metabolites. ^[2]

B6 neuropathy: from deficiency or from excess?

This is the most apparently contradictory aspect of B6: both inadequate and excessive B6 can cause peripheral neuropathy.

In deficiency: EFSA links the neurological findings to reduced synthesis of GABA, the main inhibitory neurotransmitter in the brain, and to the accumulation of tryptophan metabolites in the brain that increase seizure tendency. ^[2]

In excess: EFSA 2023 considers the association between excess B6 and peripheral neuropathy well established. In the study by Dalton and Dalton (1987), of 172 women who used B6 supplements and presented to a clinic for PMS, 103 (60%) had neurological symptoms. In all the women included in the study, serum PLP was above 18 ng/mL (72.8 nmol/L); the proportion exceeding the test’s upper limit of 34 ng/mL (137.5 nmol/L) was 70% in cases and 55% in controls. That is, neuropathy symptoms were seen with high, not low, PLP. When the supplement was stopped, 55% improved partially or completely at 3 months, and all improved at 6 months. ^[3]

Possible mechanism: The review by Hadtstein and Vrolijk proposes that excess pyridoxine causes preferential damage to sensory neurons; that high circulating pyridoxine, by inhibiting the enzyme pyridoxal kinase, may have produced a picture similar to the sensory neuropathy seen in genetic deficiency of this enzyme. The authors state that the mechanism is still unknown. ^[4] In other words, “excess pyridoxine may behave like a functional PLP deficiency” is a hypothesis, not a proven mechanism.

The practical conclusion is this: numbness, tingling or a balance problem alone does not show B6 deficiency or excess. To distinguish, B6 use history, the total amount in products, medications, other causes of neuropathy (e.g., B12 deficiency, diabetes) and, if necessary, measurement are evaluated together; this evaluation is made by a physician.

What is done in deficiency?

The cause of the deficiency (diet, absorption, alcohol, medication, kidney disease) is evaluated, and the physician decides whether replacement is needed. This page does not recommend an amount; for the upper limit there are two very different values: 12 mg/day (EFSA 2023) and 100 mg/day (NIH/IOM). ^[3]