Maternal Levels of Vitamin E Isoform Linked to Child Asthma

Laird Harrison

March 05, 2017

ATLANTA — Children of mothers with low levels of the vitamin E isoform alpha-tocopherol are more likely to wheeze, according to the results of a new study.

If supported by further research, this finding could lead to changes in nutritional recommendations, said Cosby A. Stone, MD, from Vanderbilt University in Nashville, Tennessee.

Vitamin E comes in eight isoforms that are generally lumped together on nutrition labels but may have different health effects, Dr Stone explained here at the American Academy of Allergy, Asthma & Immunology 2017 Annual Meeting.

These molecules play different roles in lung health, scavenging free radicals, and modifying the tone of immune responses, he said. The main isoforms found in humans are alpha- and gamma-tocopherol.

A tissue transport protein in humans "seems to selectively try to accumulate alpha-tocopherol," making it particularly interesting to study, Dr Stone told Medscape Medical News.

There is evidence for multiple benefits of alpha-tocopherol, he added. Giving it to female mice has been shown to decrease allergic lung inflammation in offspring, he reported, and in humans, it is associated with improved neonatal lung function and decreased risk of adult-onset asthma in women. It also decreases allergic lung inflammation in mice and human asthmatics.

Gamma-tocopherol has likewise been shown to decrease neutrophilic lung inflammation in rats and human asthmatics, he said.

To see how mothers' levels of alpha- and gamma-tocopherol might affect asthma, Dr Stone and colleagues followed 652 children and their mothers for the first 2 years of the child's life.

Researchers used post-pregnancy maternal samples to test for alpha- and gamma-tocopherol. Mothers then completed annual questionnaires about their children's recurrent wheezing. Wheezing was defined as wheezing in the past 12 months, use of asthma medications in the past 12 months, or a physician diagnosis of asthma.

The median age of the children at time of maternal sample collection was 50 days, and 53% of the children were girls.

Of the mothers, 61% were white and 21% were black, and 93% had used prenatal vitamins. Twenty-two percent had a history of asthma.

Children with wheezing were more likely to be born to mothers with significantly lower concentrations of alpha-tocopherol, the researchers found.

Table. Maternal Alpha-Tocopherol Levels

  Children Wheezing, n = 167 Children not Wheezing, n = 485 P value
Maternal plasma alpha-tocopherol level, median (μmol/L) 69 75 .02

It appeared that children of mothers with some gamma-tocopherol were less likely to wheeze than those whose mothers had low levels of both isoforms; however, this was not significant.

"Gamma-tocopherol levels at the lower end of the spectrum may be beneficial, but we were not able to detect it given the stronger beneficial effect of alpha-tocopherol," said Dr Stone. "We would need a larger sample size focused on the lower end of the range."

The adjusted odds ratio (OR) for alpha-tocopherol and wheezing was 0.69 (95% confidence interval [CI], 0.51 - 0.91), and for gamma-tocopherol and wheezing was 0.98 (95% CI, 0.79 - 1.22).

In a multivariable regression analysis, reduced wheezing with alpha-tocopherol was significant (P = .009), while reduced wheezing with gamma-tocopherol was not (P = .14).

On the other hand, children of mothers who had high levels of both gamma- and alpha-tocopherol were significantly more likely to wheeze than those whose mothers only had high levels of alpha-tocopherol (P = .05).

This suggests that gamma-tocopherol modifies the effect of alpha-tocopherol, said Dr Stone, and for this reason, it appears that mothers are better off with high levels of alpha-tocopherol and relatively low levels of gamma-tocopherol.

It may be that even higher levels of alpha-tocopherol could have harmful effects, he noted, but researchers did not see this in their study.

"The main clinical point is that vitamin E is more than one thing," he said. "The isoforms may have different effects, and we have to study them to see what they are."

The main clinical point is that vitamin E is more than one thing.

Failure to separate the isoforms could explain mixed conclusions reached in other areas of research, such as coronary artery disease, dementia, and cancer, said Dr Stone.

The results of this study suggest that a trial testing alpha-tocopherol for asthma prevention is warranted. Dr Stone and colleagues are also researching correlations between vitamin E isoforms and viral infections.

Until that work is done, "if you have a pregnant women who you suspect is nutritionally compromised, it would be fine to check alpha-tocopherol, and if it's low, fix it," he said.

Dietary Sources of Vitamin E Isoforms

The primary source of vitamin E in the US diet is cooking oil, but levels of vitamin E isoforms vary from one oil to another. Sunflower and safflower oil are highest in alpha-tocopherol, while corn, soy, and canola oil are higher in gamma-tocopherol, said Dr Stone.

Corn and soy oil are abundant in the US diet, and infant and prenatal vitamins are made from these oils, he added. However, cooking oils are more reliable than supplements as a means of boosting alpha-tocopherol levels because supplement labels may not be accurate, he said. In fact, labels on supplements sometimes incorrectly list alpha-tocopherol for all isoforms of vitamin E.

Dr Stone acknowledged that there are other considerations when choosing cooking oils, such as omega-3 fatty acids. Olive oil has favorable ratios of both alpha-tocopherol and omega-3 fatty acids, he said.

In response to a question from the audience, Dr Stone said that he defined the cutoff for plasma alpha-tocopherol deficiency as 11.6 µmol/L. And he noted that four mothers in the study were below the cutoff.

"We definitely think there are moms running around who are deficient in vitamin E," he said.

No definition of gamma-tocopherol deficiency has been established, he added.

It's too early to say what you should change.

This finding could lead to new public health measures if supported by further research, said session moderator Rajesh Kumar, MD, from Northwestern University in Chicago, Illinois. But for now "it's too early to say what you should change," he told Medscape Medical News.

In his own research, Dr Kumar has found evidence that alpha-tocopherol can affect lung structure. "It probably affects the lung through inflammation as well," he said.

The study was funded by a grant from the National Institutes of Health, National Institute of Allergy and Infectious Diseases Asthma and Allergic Diseases Cooperative Research Center. Dr Stone and Dr Kumar have reported no relevant financial relationships.

American Academy of Allergy, Asthma & Immunology (AAAAI) 2017 Annual Meeting. Abstract 263. Presented March 4, 2017.


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