Sensational Misinterpretation of Published Data Creates Concern where None is Warranted

The headlines are remarkably clear — if you eat canola oil, you’ll soon not remember that you ate canola oil. The media exploded with their interpretation of a peer-reviewed scientific report in the cleverly named journal Scientific Reports. The spate of internet articles from any Google search indicates the link between canola oil and leaky memory gaskets is as clear as canola oil.

The news is pretty damn certain this stuff is brain poison! The scientific paper has a rather different view.

But wait, canola oil has been touted as a healthy oil with a composition similar to olive oil. How can this be true in light of the new findings?

The answer is pretty simple. The news media took the liberty of overstepping the data actually presented in the scientific report in Scientific Reports. What did the paper actually say?

First, what is canola oil? Like all things Canadian it is a friendly version of something else, in this case vegetable oil. It is extracted from the seeds of Brassica napus, a plant in the same family as broccoli and cauliflower. Somewhere along the line cunning marketers changed the name to “canola” from “oilseed rape”, hence canola oil replaced rapeseed oil. This next part is true. I was visiting a colleague in China and was touring the campus. The buildings had Chinese names on them with English translations. There was a building where they did canola research proudly called “The Rape Institute”. I suggested that they fix that.

I first met canola in 1989 while working as a summer intern for Cargill Hybrid Seeds. I learned that it was an up-and-coming crop because of its favorable healthy oil composition, containing a high proportion of monounsaturated fat. Since then I’ve used it all the time, I think the farms are gorgeous and I know some canola farmers and folks in the industry. They all eat a lot of canola oil and seem to remember things pretty well.

The referenced study was performed at Temple University by Elisabetta Lauretti and Domenico Pratico. The authors note that Mediterranean populations have lower incidence of Alzheimer’s Disease (AD) compared to other populations and that the major fat in their diet is olive oil. Olive oil has a composition profile very similar to canola oil, but canola oil is much less expensive. So they tested the hypothesis that canola oil had similar health benefits (but they didn’t state it that way, but the work does seem to have the slight odor of an a priori teardown).

The experiment examined mice that were genetically engineered to develop histopathological markers of AD progression — signatures called amyloid plaques and neurofibrillary tangles, along with associated memory foibles. Six-month-old mice were fed standard mouse food, or the same mouse food with canola oil, for six months. They were then asked to do some memory tests, and eventually their brains were examined for structural and biochemical evidence of AD-like pathology. What were the results?

Slight Difference in One Aspect of a Behavior Test. The results show that canola oil eating mice perform slightly different in the Y-maze. This is a test where a mouse walks to the fork in the road and then decides which fork to take. Rodents apparently like to explore new space, so the tendency is to alternate between both forks in the maze. The ones that ate canola oil didn’t alternate as much as the non-oil eaters, probably about 20% less, an amount that was noted as statistically different. In the other two tests, including the Morris Water Maze, mice of all diets performed comparably.

Okay, so out of six measures and three different tests, the oil eating mice were different for one test, and showed about a 20% difference in behavior. I guess that’s the alleged cognitive deficit. In the discussion the authors refer to this as “significant deficits of working memory”, but I’m unsure how that slight difference in one test indicates that.

It is interesting to note that the same transgenic mice prone to AD were also used in the group’s previous studies. In Lauretti et al. (2015) the control mice navigated the Y-maze with what appears to be a ~65% alternation frequency. In this 2017 paper the control mice did this with what looks like about ~45% alternation frequency, so the difference in the controls between experiments is greater than the difference between the control and the experimental within the current work, suggesting that this can be a noisy test. The authors did not report the age of the mice (they were at least “7–8 months old” in the 2015 test) so maybe the mice in the current test were older and more diseased, so that could explain that difference. It is not clear from the materials presented.

A Decrease in a Beta-Amyloid Type. The next test examines the levels of amyloid beta species. These are small proteins, in this case 40 and 42 amino acids long, referred to as Aβ1–40 and Aβ1–42. The amyloid hypothesis says that plaques formed by the misfolding and/or aggregation of these peptides are the basis of pathology and associated manifestations like senility. The Aβ1–42 form is considered to be much more likely to form amyloid plaques, and has different intracellular compartmentation.

The authors found no significant differences in extractable levels of these proteins, except for lower levels of Aβ1–40 in a fraction extracted with formic acid. Formic acid has been used to solubilize the proteins resident in the plaques, and indicates those typically associated with senility. That is compared to the RIPA extraction which liberates all Aβ’s, allowing comparison of total Aβ vs those bound in plaques. In Figure 2A the authors show a significantly lower level of Aβ1–40 in oil eating mice compared to controls.

The rest of the figure shows that other measures are comparable in all mice when averaged, even though there is variation seen in the assay (a ‘western blot’) for proteins associated with Aβ presence and clearance, suggesting differences between individuals (they assayed four mice for each). No it suggests that variation within the small experimental groups is quite rangy, and makes it difficult to find firm statistical significance.

No Effect on Tau Protein. Tau is a protein also associated with AD particularly as tau deposits. Some have hypothesized that Tau is the actual culprit in memory loss, as asymptomatic brains are seen loaded with beta amyloid plaques (Brier et al., 2016). In this work the authors analyzed the phosphorylated form of Tau, which apparently is present in plaques in the AD mouse model. There were no differences between treatment and the control. This contrasts with olive oil where they saw less Tau protein in previous work (Lauretti et al., 2017).

Less PSD95 Protein. PSD95 is what’s known as a scaffold protein. It coordinates post-synaptic clustering of neurotransmitter receptors, and decreased levels have been associated with aging, AD and neuropathology (Savioz et al., 2014). While thought of as a marker of neural integrity, results are contradictory, suggesting tissue-specific and environmental influences. In this case the oil eating group has lower levels of PSD95, which supports the authors’ conclusion of canola oil leading to specific neurological consequences.

No Difference in Inflammation Markers. The authors then examined levels of GFAP and IBA1, proteins associated with central nervous system damage and breakdown of cells. No significant differences were observed.

No Differences in Other AD Markers. CREB is a transcription factor (in this case) meaning it turns genes on. It is present in different forms, and is sometimes phosphorylated. CREB and products from its downstream target genes are associated with AD pathology. There is no difference observed between the canola oil eaters and controls.

No Differences in Autophagy Proteins. A number of proteins are known to play a role in autophagy, that is (loosely) turnover of specific proteins in the cell. No differences were observed in the process here, but the authors cite a reference where olive oil induced autophagy in muscle cells relative to palm oil (Oliván et al., 2014), which seems like a tangential reference in a paper about canola oil and brain proteins.

Synthesis. In my opinion the authors do oversell this a little in their conclusion. While they correctly state that there is a difference in amyloid 40/42 ratio, they also state “negative effect” on memory, which is shown as a statistically significant, yet minor effect on a single test. Other tests are consistent with their hypothesis of canola=no good, and their final statement of “our findings (in AD model mice) do not provide support to some of the current ideas suggesting healthy benefits deriving from the regular consumption of canola oil” does not say that the product causes dementia in humans.

Of course, the healthy benefits were not necessarily claimed to be neuroprotective. I’ve always thought of high monounsaturated fats in the diet as having cardiac benefit over saturated fats, so I’m not sold that their AD tests were germane to the proposed health benefits claimed by canola oil producers.

Weight Gain. Canola oil consuming mice did weigh more at the end of the experiment. I guess that would be expected. The authors did not note if the mice were given the same caloric content in treatment and control, and if I’m a mouse and I can eat as much canola oil as I wanted, I might put on a few grams as well, especially because mice don’t have a Speedo Season. A similar weight gain was observed in the same group’s experiments with olive oil (Lauretti et al., 2017).

Overall. When looking at this paper I see a good lab with competence and expertise in the area performing a test on a small number of mice, where they give standard lab chow and lab chow containing significant amount of canola oil. The effects seen cannot be directly attributed to canola oil per se, but to oil consumption, or increased calories in the diet, or just being overweight. Obesity is associated with at least certain forms of AD, so seeing specific markers and mild impairment in an AD mouse model is probably not surprising. This also was the first scientific paper I’ve ever read that uses the word “propeller” not referring to a boat part. That’s cool.

Rationale for the Study. The group has done previous evaluations on olive oil, and has shown benefit on the tests in this mouse line. They also have shown positive effects on the various disease state markers. Apparently canola oil does not behave the same way that olive oil did, which is interesting because the two are so similar in composition, at least at the fatty acid level. There could be other minor chemicals imparting the effects.

It is not surprising that old fat mice fed a massive amount of oil for half their life exhibit slightly different behaviors and show markers associated with neurological disease and aging. What is surprising is that the results are so different from the olive oil results when the two are so similar in composition. It is indeed curious why they didn’t include olive oil as a control. It is an intuitive one in retrospect, and would have been really helpful. It would show that the results in canola oil were due to some specific characteristic of the oil — something not in olive oil, such as higher levels of alpha-linolenic acid.

The Runaway Interpretation. The figure up top says with great certainty that canola oil is “linked to dementia” and worsens Alzheimer’s symptoms. Clearly that was not the conclusion of the authors and in no way reflects what the data present. What the data show is that mice fed more calories from oil that get overweight behave slightly differently in one of several neurological tests and has a subset of biochemical changes that are consistent with AD, in a mouse that is designed to have neurological modifications that are consistent with AD.

The paper does not show in any way that there is a causal link to disease in humans. Not even close.

The interwebs have gone berzerkers.

Why Would the Media Get This So Wrong? My feeling is that it is our continued cultural war on food. Canola is a new crop, made from selective breeding in Canada to produce a new high-oil seed. It also is genetically engineered, and the web is alive and well with claims that it is the magical “GMO” entity that is causing dementia. Just go take a peek for that.

A relatively new crop, using genetic engineering, to make an oil used on a massive scale? It is the perfect punching bag for food activists that don’t understand the chemistry, but certainly know how to over-interpret the results of a reasonable, but statistically underpowered report.

In researching this topic I was surprised to see the plethora of anti-canola rhetoric on the web. Misinterpreting the data from this paper fits well into that agenda.

And the robots are alive and sensational too!

In Conclusion. The test that directly compares multiple kinds of oils with controls will be most welcome. Others have done such studies using olive and palm oils, and shown some nice, direct comparisons. For now, I’ll keep eating canola oil. No problem here, as these results do not indicate any ill effect on human health, and show slight effects on messed up mice.

Again, just overstatement of a sensation hungry media blowing up more nonsense about the safest food supply in human history.