Reader Challenges Our Facts -- Scientist Replies To Criticism
15 March 2001

SupplementQuality.com received criticism from a reader that our recent interview with Professor Robert Reynolds contained inaccuracies. In particular, the reader said "the B6 level was set using more than one baby," and called this "an example of one inaccurate anecdote" in our interview of 14 February 2001 where Professor Reynolds says:

"The 1989 RDA for vitamin B6 in infants is based on a single infant. And if you read the paper carefully, it looks like that infant was born to an abnormal mother. But [the Institute of Medicine] went and did an RDA anyway."

Even though the Institute of Medicine issued a new edition for the B vitamins in 2000, the 1989 RDA is still used on labels today. The new guidelines will not be used until the Institute completes its next report (on macronutrients).

We asked Professor Reynolds about our reader's challenge to his facts. His reply is both detailed and thorough. First, he quotes the 1989 (10th edition) RDA book, which states on pages 145-146:

"The vitamin B-6 content and vitamin-to-protein ratio is generally low in milk from nonsupplemented women, and there is evidence of vitamin B-6 deficiency symptoms in infants breastfed by women whose intakes are less than 2.0 mg/day and whose milk contains less than 0.1 mg of vitamin B-6 per day (Kirksey et al, 1981; Kirksey and Udipi, 1985; McCoy et al, 1985). In healthy babies, vitamin B-6 intakes of 0.3 mg/day protected against abnormal excretion of tryptophan metabolites following a test load (Bessey et al, 1957). General experience with proprietary formulas suggests that metabolic requirements are satisfied if the vitamin is present in amounts of 0.015 mg/g of protein or 0.04 mg/100 kcal (AAP, 1976; McCoy, 1978). The present subcommittee maintains the vitamin B-6 recommendations of the ninth edition of the RDA -- 0.3 mg/day during the first 6 months of infancy and 0.6 mg/day for older infants."

Next, he looks at the references cited, one at a time. The first is Kirksey et al (1981), which is a chapter entitled "The Vitamin B-6 Content of Human Milk" in a book that Reynolds co-edited. Reynolds says:

"In that chapter, Kirksey gives lots of data, most of which is devoted to the vitamin content at different stages of lactation and effect of maternal dietary intake of the vitamin on the vitamin content in her milk, but there is nothing related to the vitamin requirements for infants between 0 and 3 months of age!"

The second reference is Kirksey and Udipi (1985), which is a chapter entitled "Vitamin B-6 in Human Pregnancy and Lactation" in another book that was co-edited by Reynolds. Reynolds says:

"In that chapter, they look at Apgar scores at delivery, at p50 values at delivery, at the distribution of the different forms of the vitamin in human milk, and the relationship between maternal dietary intake of the vitamin and how that is reflected in the amount of the vitamin delivered to her breast-fed infant, and how that compares to the 1980 RDA (not how it compares to the requirement of her infant, but to the RDA!). However, there is nothing about the requirements of the infants!"

The third citation, McCoy et al (1985), also appears in the 1985 book that Reynolds co-edited. This chapter is entitled "Vitamin B-6 Intake and Whole Blood Levels of Breast and Formula Fed Infants: Serial Whole Blood Vitamin B-6 Levels in Premature Infants." Reynolds says:

"First off, notice that these were premature infants -- not full term infants. We know that premies have lots of problems, not just with vitamin B-6, and it's not clear how to separate each of the confounding factors from one another. But again, there is nothing about the requirements of infants 0 to 3 months of age -- premature delivery or full term delivery. This paper discusses only the effects of supplemental vitamin intake by the mothers and how this is reflected in the blood of the infant. This is not requirements! This is biochemistry."

McCoy's other paper (1978) is also a chapter in a book (one that Reynolds did not co-edit). Reynolds says:

"On page 258, [McCoy] states, 'A careful survey of the literature failed to reveal experimental studies linking vitamin B-6 requirements to protein intake in infants or children.' He then goes on to discuss two early papers -- one by Snyderman et al (1953) and one by Bessey (the one cited above in the 1989 RDA, to be discussed next).

"The Snyderman paper places mentally retarded infants (or as they called them, severely mentally defective) on vitamin B-6 devoid diets and sees when they begin to show symptoms of deficiency. It's a rather gross paper to read, especially if you love kids. (This experiment could not be done today.) In that paper, they describe what happened to one subject: 'On the 76th day of deprivation, subject M.L. suffered a series of severe convulsions . . . (a description of the convulsions follows). Aside from oxygen during seizure, no other therapy was given until he received 50 mg of pyridoxine hydrochloride intravenously. Within three hours he started to show signs of improvement.'

"I maintain that giving a single 50 mg bolus of PN does not constitute determining the requirement of that infant. It was a classic depletion/repletion study -- not a study designed to determine the requirement of the infant."

Concerning AAP 1976, Reynolds says:

"The AAP citation refers to the vitamin B-6/protein ratio and is not relevant to any basic research (of their own) on the requirement of the vitamin for infants -- just the most appropriate vitamin to protein ratio."

Reynolds then examines the last of the cited papers, that of Bessey et al (1957), and says:

"They studied two groups of infants. The first was formula-fed infants with seizures -- where the vitamin in the formula was accidentally destroyed by over-sterilization. The second group was 'Two breast-fed infants with seizures (Cases 6 and 7) who had received neither vitamin supplements nor solid foods in significant amounts. In one infant (Case 6), convulsions ceased after the diet was changed to an evaporated milk mixture; in the other, the same response followed the therapeutic administration of pyridoxine hydrochloride; in both, there was biochemical evidence of deficiency of vitamin B-6. Analysis of the human milk from Case 7 indicated an extremely low content of vitamin B-6.'"

Reynolds states that Bessey et al also studied three other groups, but these are not relevant to this discussion because they were controls and older children. Reynolds continues:

"Bessey et al gave increasing amounts of the vitamin to infants, then gave them a tryptophan load test to see where their urinary excretion of the tryptophan metabolites 'normalized' (whatever that means). They stated '. . . until a level of intake of the vitamin was found which just prevented excretion of xanthurenic acid after a test dose of DL-tryptophan of 0.54 gm/kg.'"

Reynolds doesn't know why they felt this criterion would indicate the infant's requirement for B-6 -- but that is the subject of a different discussion. Concerning the Bessey et al study, Reynolds continues:

"The relevant infants (data contained in Table II) are Cases 6 and 7, as mentioned above. Case 6 had no measure of the intake of the vitamin! However, when it was given a formula which provided 0.26 mg vitamin B-6 per day, convulsions ceased. For Case 7, they did determine that this breast-fed infant was receiving 0.067 mg of the vitamin per day (from analysis of the mother's milk), and its convulsions ceased when given the same formula of 0.26 mg/day.

"Unless my math is way off, I count a grand total of one infant in which the initial intake was determined (and which had a clinical symptom of a vitamin B-6 deficiency) and then a single level of the vitamin which caused the deficiency symptom to disappear. So, all we know is that the requirement is somewhere between 0.067 and 0.26 mg/day, and those numbers come from one infant. In its infinite wisdom, the RDA committee took this 0.26 mg/day and rounded it up to 0.3 mg/day. Voila! The RDA for infants 0 to 3 months of age."

Reynolds hopes this clarifies the issue raised by the reader, and says, "It's too bad when otherwise responsible persons fail to carefully read the literature, especially persons on the RDA subcommittes."

"RDAs and safe upper levels are more political than scientific." Interview with Professor Robert Reynolds of the University of Illinois at Chicago.