Will our desire for seafood and non-stick frying pans compromise the effectiveness of vaccines intended to protect us from nasty diseases? Research published today in the Journal of the American Medical Association (JAMA) will likely be represented in the media that way, but this excellent study isn’t quite so simple.
Before talking about the study itself, let me set up a bit of background.
Trace levels of certain synthetic chemicals in our environment and food can be potentially harmful, but we need to maintain some degree of perspective; the most important toxicological maxim is – it’s the dose that makes the poison.
Chemicals in the environment
While there are a number of synthetic (and very scary sounding) chemicals in our environment, only some have the potential to cause harm. One of the particularly worrisome groups is persistent organic pollutants (POPs). These are a group of chemicals that break down very slowly, and have the ability to accumulate in animal tissue. This is important because while contaminant levels in water, soil or air may be low, continuous exposure may have them accumulate to toxic levels in the body.
One of the least well-understood groups of these chemicals are perfluorinated compounds. These are basically long carbon chains with hydrogen replaced by fluorine. Perfluorinated compounds (PFCs) are used as water and stain repellents, and in making Teflon.
These chemicals are widely distributed in the environment, as well as in animals and humans. They bind to the proteins in animals' bodies, and are very persistent, which means it can take over four years for half of a single dose of PFC to be eliminated from a human body (if you were to swallow 10 mg of PFC, half that amount would still be in your body four years later).
The ability of these compounds to accumulate in animals is important, because their major source for humans is from eating flesh, particularly fish. But while high concentrations are clearly toxic, the effect of levels similar to what people are generally exposed to is less clear.
One particular worry is the effect PFCs have on the immune system. Some studies in mice suggest that levels of perfluorinated compounds within the range seen in humans may reduce the ability of the immune system to respond to infection, but others have found much higher levels are needed to make an impact. The differences in these studies may be due to the strain of mice used, or how the perfluorinated compound was administered.
The latest study
This new JAMA study attempts to throw light on the PFC effect by examining a real-world outcome – our ability to mount an immune response to vaccination. Researchers measured the antibody response in children vaccinated against diphtheria and tetanus. And they measured the levels of perfluorinated compounds (PFCs) in their blood, and in stored samples of their mothers’ blood from when the children were born.
The children and their mothers lived on the Faroe Islands, a Danish protectorate halfway between Scotland and Iceland. This is important because there are good medical records for the children, and the islanders have a diet high in marine foods, which potentially exposes them to high levels of PFCs.
One of the hardest things to be certain about in this kind of research is whether the levels of a compound measured in a single blood sample accurately represents the levels over many years. If you measure someone’s blood sample at five years of age, does it remain the same or is it higher or lower later in life?
But because the researchers measured the mothers' blood levels as well as that of the children and because these compounds are expelled from the body very slowly (remember: four years or more for half a single dose), it’s likely the concentrations of PFCs the children were exposed to over the first seven years of their life (when their vaccination responses were monitored by the researchers) were not wildly different to the levels measured when they were five years old (when they were given their vaccination booster shots).
What they found
The researchers found that increasing levels of PFCs correlated with decreased antibody levels in response to vaccination. Importantly, the levels of PFCs in the children’s blood were similar to levels found in other populations, such as the United States. But how concerned should we be about this result?
Firstly, correlation is not causation. Sure, it may waggle its eyebrows suggestively while mouthing “look over there”, but we need to be very careful about interpreting these results. Because of their seafood-rich diet, the Faroese children are exposed to a lot of chemicals that could potentially cause problems.
And while the level of PFC may be similar between Faroese and other children, the source of the contaminant may be different. That is, PFC levels in Faroese kids may simply be a marker for high seafood consumption, and the antibody problems may be due to other reasons. The only way to confirm the effect of PFC on vaccine response would be to examine the immune response of other children with similar levels of PFC in their blood but who are not exposed to other contaminants.
Indeed, the same researchers had previously shown that polychlorinated biphenyl (a chemical that makes plastics more mouldable) levels in Faroese children correlated with low vaccine response. So for this study, they also measured polychlorinated biphenyl levels and tried to adjust for it in their results.
But again, given the number of contaminants the children were exposed to through their diet, more evidence is needed before we can decisively say PFCs are the reason for their decreased antibody response. The authors of the study say this themselves.
What does it all mean?
From the point of view of those who want to eat lots of fish, this may seem like nitpicking; we already know that we ought to limit fish consumption because of methyl mercury contamination, especially in top predators like tuna.
The other issue is interpreting the fall in antibody concentrations – while there’s a statistically significant fall in antibody levels, its clinical significance is unclear. It’s generally considered that for decent protection against infection you need antibody levels greater than 0.1 IU/mL (international units per millilitre) in your blood, but even at the highest levels of PFCs the antibody levels never really fall below 0.25 IU/mL. IU is a measure of how much antibody is in your blood.
If we extrapolate from the Faroese to other communities going on blood concentrations alone, then 95% of all children would be well protected by vaccination despite exposure to PFCs.
But this brings us to another issue: can we actually extrapolate from the Faroese? Despite the children’s blood concentrations being similar to those of children in the United States, the higher intake of other chemicals such as polychlorinated biphenyls and methyl mercury may significantly alter their immune response.
This is an important paper but it’s only the first step in understanding the effect of PFCs on human immunity. The authors themselves say this. We may see some scary headlines as a result of it but the data presented suggests the vast majority of children will be well protected by vaccination despite exposure to PFCs.