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Third of newborn rats died if mums ate bad fish oil

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A third of pups born to rats fed high doses of very rancid fish oil during pregnancy did not survive beyond two days, a New Zealand-authored study finds. The researchers say that because the pups of mums fed normal fish oil as an omega-3 supplement were fine, this suggests it is the chemicals the omega-3 fatty acids break down into during oxidation that have a lethal effect, rather than the fish oil itself. However experts say this is very unlikely to happen for human mums-to-be because the bad oil was intentionally oxidised to an extreme level and the rats ate the equivalent of 40ml (about three tablespoons) of fish oil every day, which are both unrealistic.

Journal/conference: American Journal of Physiology

Organisation/s: Liggins Institute, University of Auckland

Media Release

From: Liggins Institute, University of Auckland

Three in ten rat offspring die after mothers fed oxidised fish oil: study

Highly oxidised (“off”) fish oil fed to pregnant rats caused almost 30 percent of their newborns to die, a New Zealand study has found.

The researchers wanted to investigate the health effects of “off” fish oil after an earlier study they did found most fish oil supplements sold in New Zealand were off to some degree.

Female rats in the latest study were given either unoxidised fish oil, a highly oxidised fish oil, or water (the control group) daily throughout pregnancy. Almost 30 percent of baby rats born to mothers who had highly oxidised oil died within the first two days.

Giving pregnant rats the unoxidised fish oil did not increase mortality rates in their babies, indicating that the lethal effect on newborns came from the chemicals that omega-3 fatty acids break down into during oxidation.

Omega-3 fatty acids are known to be chemically fragile or “unstable”, and can easily break down when exposed to natural conditions such as light, heat and oxygen.

The earlier, highly read study, published in Scientific Reports last year, tested 36 brands of fish oil supplements capsules. It used the international industry standard tests of oxidation. Eighty-three percent were oxidised beyond international recommended levels. How “off” they were had nothing to do with best-before date, price, or the country they came from.

Four studies from North America, South Africa and Europe have also uncovered high levels of oxidation in fish oil supplements.

“Once we discovered so many supplements were oxidised, we decided to focus on the health effects of oxidised fish oil during and after pregnancy,” says research fellow Dr Ben Albert, from the Liggins Institute at the University of Auckland.

“Pregnancy is a critical period when considering the safety of medications, and the same should apply to dietary supplements. Chemicals that may be harmless to mothers could potentially disrupt developmental processes in the womb.”

“We were surprised by the death rate,” says study lead Professor Wayne Cutfield, also from the Liggins Institute. “We’d expected some negative health effects on the rat offspring, but we didn’t expect them to die.”

“We don’t know exactly why the newborn rats died,” Dr Albert says. “Because we didn’t expect them to die, we didn’t design the study to look for reasons.”

At weaning, the mothers given oxidised fish oil also had greater insulin resistance, which in humans can lead to type 2 diabetes.

Dr Albert emphasises that the results of this study cannot be directly applied to humans.

“Obviously, rats are not humans. Also, it’s important to note that the fish oil dose we gave to the rats was higher than doses humans take, but this dose is commonly used in fish oil studies in rats.

“Also, the level of oxidisation was at least double what we detected in most products in our earlier study of fish oil supplements. Commonly, a more potent formulation is given to determine if there is any effect. Then, you design follow-up experiments to test different doses at different degrees, to see exactly when the effects start to show up,” he said.

“In future studies, we hope to examine what happens in pregnant rats when you vary how oxidised the fish oil is, and to understand exactly how the oxidised fish oil harms the baby rats.”

Up to one in five New Zealand women take fish oil supplements during pregnancy, according to the latest estimate.

“While some women take fish oil during pregnancy to try to improve the development of their child’s brain, there’s no convincing evidence that this helps,” says Dr Albert.

“Oxidised fish oil is unlikely to carry serious health risks in humans,” says Professor Cutfield.

“But at the moment, we just don’t know the health risks to the unborn baby. And our first study showed it’s not possible to know if fish oil is oxidised when we buy it. This suggests it may be wiser for women not to take fish oil supplements in pregnancy.

“Clearly, further research is needed to assess any risk to humans,” he says. “In the meantime, pregnant women might consider eating fresh fish for omega-3 oils.”

Key points:

  • Main finding: 30 percent of rat newborns died within two days of birth after their mothers were fed oxidised (“off”) fish oil during pregnancy
  • Giving unoxidised fish oil to pregnant rats did not increase mortality rates in their offspring
  • Follows earlier study by the same team that found most fish oil supplements on the market in New Zealand were oxidised to varying degrees in the sample tested; the degree of oxidisation had nothing to do with price, use-by date or country of origin
  • Five independent studies, including ours, conducted across four continents that all show frequent oxidation above recommended limits
  • Omega-3 fatty oils, for which fish oil supplements are taken, easily break down (oxidise) when exposed to natural conditions such as light, heat and oxygen
  • Further research is needed to assess any potential risk of “off” fish oil supplements to pregnant women and their babies

Attachments:

  • Liggins Institute, University of Auckland
    Fish-Oil-in-Pregnancy-MR-final2.doc, 77.0 KB
  • American Physiological Society
    Web page

Expert Reaction

These comments have been collated by the Science Media Centre to provide a variety of expert perspectives on this issue. Feel free to use these quotes in your stories. Views expressed are the personal opinions of the experts named. They do not represent the views of the SMC or any other organisation unless specifically stated.

Dr Peter Nichols, science advisor, Omega-3 Centre, senior principal research scientist, CSIRO. Australia

The wider scientific community was surprised and highly disappointed by the original 2015 Scientific Reports paper from University of Auckland researchers. The Australian Therapeutic Goods Administration (TGA) performed follow-up analyses and all tested oils were not oxidised and omega-3 content met label claims.

For this new study, the justification appears to be driven by the Scientific Reports paper, which remains in the strongest doubt and dispute. The new paper uses heavily oxidised oil that the New Zealand authors prepared. As Australian and New Zealand fish oils are not heavily oxidised, the study is seen as not relevant.

The dose used is equated to 40 mL per day for a human consumer. This dose is seen as exceptionally excessive. Few consumers would be taking more than 5-10 g per day.

The unoxidised oil actually and interestingly shows improvement in the new paper, versus the control treatment, although little is stated by the authors on this aspect.

Last updated: 03 Nov 2016 4:31pm
Professor Lynnette Ferguson, professor of nutrition, Auckland Cancer Society Research Centre

I was very concerned about the original paper, which they continually cite, and claim shows that most over the counter omega-3 supplements in New Zealand are oxidised. This conflicts with the data from the omega-3 centre in Australia.

Having done analytical work with these compounds myself, I am only too conscious that there are some technical difficulties in getting accurate results.
 
The original problems are compounded by this paper. It uses oxidised oil that has had oxygen bubbled through it for 30 days plus light exposure.

This is far beyond the level of contamination their earlier paper suggested was present in any New Zealand supplement. This oil was fed to animals at concentrations way beyond those appropriate to humans.
 
If you look at their data, there was actually a minor benefit shown from the un-oxidised oil, suggesting a benefit to pregnant women of supplementation.

Last updated: 03 Nov 2016 4:12pm
Professor Murray Skeaff, professor in human nutrition, University of Otago

Cutfield and his colleagues bubbled pure oxygen through fish oils for 30 days under a fluorescent light, then fed the highly rancid and oxidised fish oil to pregnant rats. The rancid fish oil killed close to 30% of the pups born to the rat mothers and harmed the health of the pups that survived.


What relevance does this research in rats have for the health of pregnant women who take fish oil supplements? An educated guess, probably none, but curiosity demands an attempt to answer the question.

The fish oils fed to the rats were oxidised under conditions so extreme as to bear almost no resemblance to fish oils consumed by humans. Nevertheless, the high mortality rate amongst pups born to rat mothers fed the oxidised oils proves that one or more compounds were produced in the fish oil during oxidation that are toxic to the rat.

What are these compounds, are they also harmful to humans, and are they present in commercially manufactured fish oil supplements? Unfortunately, there is nothing in the research by Cutfield that helps to answer these questions but surely they will try and find an answer.

Last updated: 03 Nov 2016 4:03pm

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