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Should You Be Concerned About B6 Toxicity?

Posted on : June 16, 2023 by Hardy Nutritionals® No Comments

Question from a customer:

"I am wondering why Hardy Nutritionals uses the pyridoxine hydrochloride form of B6 and if it is safe?"


Daily Essential Nutrients (DEN) provides 70 milligrams of pyridoxine at the full dose of 12 capsules per day, which is considered safe for children and adults. We have greatly reduced the pyridoxine in favor of P5P in our newest formulation, Daily Essential Nutrients with Added Vitamers, so if anyone is concerned about vitamin B6 toxicity, they can have peace of mind simply by choosing the DEN+V formula instead of the original DEN formula.

What is Vitamin B6?

Vitamin B6 is the generic name for six compounds with vitamin B6 activity: pyridoxine, an alcohol; pyridoxal, an aldehyde; and pyridoxamine, which contains an amino group; and their respective 5’-phosphate esters. Pyridoxal 5’ phosphate (PLP) and pyridoxamine 5’ phosphate (PMP) are the active coenzyme forms of vitamin B6. Substantial proportions of the naturally occurring pyridoxine in fruits, vegetables, and grains exist in glycosylated forms that exhibit reduced bioavailability. [1]

What We Know About Vitamin B6 Metabolism

The ability to metabolize pyridoxine varies greatly between individuals, and it is likely that only unmetabolized pyridoxine causes vitamin B6 toxicity and not P5P, which is the active coenzyme form of the vitamin. 

The human body absorbs vitamin B6 in the small intestine. Phosphorylated forms of the vitamin are dephosphorylated, and the pool of free vitamin B6 is absorbed by passive diffusion.

This means that in order to be absorbed, the B6 molecule is reduced to a pyridoxine base first and is then re-phosphorylated after absorption.

Vitamin B6 is available in multivitamins, in supplements containing other B complex vitamins, and as a stand-alone supplement. The most common vitamin B6 form found in supplements is pyridoxine (in the form of pyridoxine hydrochloride [HCl]), although some supplements contain PLP (pyridoxal phosphate).  Absorption of vitamin B6 from supplements is similar to that from food sources and does not differ substantially among the various forms of supplements. Although the body absorbs large pharmacological doses of vitamin B6 well, it quickly eliminates most of the vitamin in the urine.

What We Know About Health Risks From Excessive Vitamin B6

Chronic administration of 1–6 grams oral pyridoxine per day for 12–40 months can cause severe and progressive sensory neuropathy characterized by ataxia (loss of control of bodily movements). Symptom severity appears to be dose-dependent, and the symptoms usually stop if the patient discontinues the pyridoxine supplements as soon as the neurologic symptoms appear. Other effects of excessive vitamin B6 intakes include painful, disfiguring dermatological lesions; photosensitivity; and gastrointestinal symptoms, such as nausea and heartburn.

The FNB (Food and Nutrition Board) has established ULs (Upper Limits) for vitamin B6 that apply to both food and supplement intakes. The FNB noted that although several reports show sensory neuropathy occurring at doses lower than 500 mg/day, studies in patients treated with vitamin B6 (average dose of 200 mg/day) for up to 5 years found no evidence of this effect..

How Much B6 is Considered Safe?
In the Dietary Reference Intakes published by the Institute of Medicine in the United States, sensory neuropathy is identified as the most critical of the vitamin B6 adverse toxicity effects and the best documented. The first clinical reports of vitamin B6 toxicity documented peripheral sensory neuropathy at a dose of 1-6 grams/day for 2-40 months, and the expert review panel concluded that “the risk of developing sensory neuropathy decreases quite rapidly at doses below one g/day.”

However, the DRI publication acknowledges that the dose at which pyridoxine can cause toxicity varies greatly. After reviewing a broad swath of data, the expert panel estimated a No Observed Adverse Event Level (NOAEL) at a pyridoxine intake of 200 mg/day (unlikely to cause adverse events in most individuals). They also estimate a Lowest Observed Adverse Event Level (LOAEL) of 500 mg/day in spite of reports of neuropathy at doses lower than 500 mg/day. In fact, there are reports of pyridoxine-induced neuropathy at doses even lower than 200 mg/day, but this data was not strong, as it either did not confirm by clinical evaluation the purported toxicity symptoms, did not confirm with certainty the dose, or did not show causality. They concluded that 100mg/day is likely safe to consume chronically (i.e., the Tolerable Upper Level, or UL) for adults who have no special considerations.

However, since “special considerations” do exist (such as genetic limitations in B6 metabolism), the IOM recommendations will not be generalizable to everyone. There are many factors which could either sensitize a person to vitamin B6 toxicity at doses lower than what is tolerated by the majority of individuals or increase their vitamin B6 requirements.  These factors include genetics, the use of certain medications, certain disorders, adequacy of other nutrients, and duration of use. 

There are anecdotal self-reports of possible B6 toxicity at doses as low as 50 mg or lower, but the lowest-dose peer-reviewed clinical report of vitamin B6 toxicity we have found is 100 mg/day, and it was only after many years of use at this dose that toxicity symptoms emerged ( 

Daily Essential Nutrients With Added Vitamers is The Best Choice For Vitamin B6 Sensitive Individuals

In summary, based on the scientific literature and our extensive experience, the large majority of individuals will not experience vitamin B6 toxicity even from 12-15 capsules per day of the original Daily Essential Nutrients formula, which contains pyridoxine. But a very few individuals with special limitations (known or unknown) to vitamin B6 metabolism may experience toxicity symptoms at these doses. For this reason, we have dramatically reduced the pyridoxine vitamer to only 8mg per serving in our Daily Essential Nutrients with Added Vitamers formula (a total of 24 mg/day at a daily dose of 12 capsules per day) in order to offer the benefits of Daily Essential Nutrients to those who may have very low-dose sensitivity to pyridoxine. The remainder of the vitamin B6 in this new version of DEN is P5P, which should not cause vitamin B6 toxicity even at much higher doses. If diminished vitamin B6 metabolism is known or suspected, the DEN with Added Vitamers formula would be indicated over the original version of the formula.


Hardy Nutritionals® multivitamin-mineral products are powered by our proprietary NutraTek™ mineral delivery technology, which combines each mineral with specialized organic molecules—just like nature—to optimize absorption and distribution to body cells. Our flagship supplement, Daily Essential Nutrients, is widely considered to be the most research-backed micronutrient treatment.
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