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Thursday, February 2, 2017

Nutella does not cause cancer

Nutella is a delicious chocolate spread (think chocolate peanut butter) popular in European countries such as Italy and France (Figure 1). Its primary ingredients are "sugar, modified palm oil, hazelnuts, cocoa, skimmed milk powder, whey powder, lecithin, and vanillin." Over the past few weeks, Nutella has been making the news for the wrong reasons (The Verge):
"What the study does say is that palm oil, an ingredient in Nutella, releases potentially carcinogenic chemicals when refined at high temperatures. Palm oil, derived from the fruit of palm trees, is used in plenty of food. When refined at around 200 degrees Celsius, the study says, palm oil releases a contaminant known as glycidyl fatty esters (GE) in higher levels than other vegetable oils. Previous studies have shown that GE can cause tumors in rats and mice, leading EFSA to characterize it as a “potential health risk” for children and anyone who consumes it in high amounts."
Palm oil is a primary ingredient of Nutella, and is one of the few highly saturated vegetable oils which can confer a more "buttery" consistency. During the refining and purification process, palm oil is heated to 200oC, which induces the conversion into glycidyl fatty esters (GEs). These GEs when consumed by humans are digested into glycidol, which has been classified as a Group 2A (probable) carcinogen by the International Agency for Research on Cancer (IARC). Because of this connection, the European Food Safety Authority (EFSA) labeled palm oil products (e.g. Nutella) "a potential health risk," and then the media ran with the story.

There has been a subsequent backlash with numerous articles debunking the fear-mongering about palm oil in general and Nutella more specifically. I would point to these articles from The Verge, Snopes, and ACSH.

Glycidol is an epoxide (C-O-C three-atom ether cycle; see Figure 2) that is capable of alkylating a number of compounds including DNA, which makes it a potential mutagen. This property is one reason why glycidol has caught the attention of government regulators. However, the direct evidence that glycidol is a carcinogen is weak. First, there are no studies in humans that show any increased risk of cancer. Second, the animal data are mixed with some studies showing some carcinogenesis at high concentrations, whereas other studies show no increase in cancer. Finally, the concentrations that induce cancer in animals are much higher than what a person could possibly consume (ACSH):
"The EFSA's analysis of glycidol was similar, but even more absurd: A T25 of 10.2 mg/kg bw per day for peritoneal mesothelioma in male rats was used as the reference point. In view of the genotoxic and carcinogenic potential of glycidol, a margin of exposure (MoE) approach was applied. MoE estimates were calculated by dividing the reference point of 10.2 mg/kg bw per day by the exposure levels. A MoE of 25,000 or higher was considered of low health concern. Translation: "At a dose of 10.2 mg/kg, glycidol caused abdominal membrane cancer in 25% of rats (i.e., T25). We divided that number by 25,000 to determine the safe level of consumption."
The bottom line is that even in the positive animal studies, the dose that produced the cancers was very high, and the degree of carcinogenesis was modest and not reproducible across experiments. Indeed, even after including a wide margin of exposure (MoE, i.e. divide the minimum dose that induced cancer by 25,000), the resulting threshold dose exceeded the amount a person typically consumes in a normal diet. Finally, there are many other food products that contribute more GEs to the diet than Nutella. One surprising example is baby formula, and some formula manufacturers are working to cut back on the amount of palm oil used because of the negative publicity.

The fact that glycidol is genotoxic and mutagenic certainly gives one pause. Many carcinogens are mutagens; they promote cancer by inducing mutations in the DNA of your cells. Some of these mutations may lead to the activation of oncogenes or the inactivation of tumor suppressor genes. One of the common methods of testing the mutagenicity of a chemical compound is the Ames Test in which one measures whether and at what dose a chemical will increase the mutation rate of a specific bacterial gene.

In the Ames Test, glycidol is indeed mutagenic but only at high doses in the millimolar range (link). By comparison, Group 1 carcinogens such as some dibenzopyrenes are mutagenic in the micromolar concentrations, i.e. 1000-fold lower doses. These levels are consistent with animal studies in which certain dibenzopyrenes are able to induce high levels of cancer at microgram per kg (body weight) concentrations in laboratory mice and rats, compared to the mg/kg potency of glycidol (once again an approximate 1000-fold difference; link).

In summary, the most careful analysis shows that the levels of glycidol necessary to possibly cause cancer in laboratory animals is very high which far exceeds what a person typically consumes and is roughly a thousand times less potent than known carcinogens. Animal studies have provided mixed data with some showing modest cancer induction, whereas others did not. There have been no human data to date. Moreover, Nutella is not the primary source of glycidol in the average person's diet, and you would have to consume jars and jars of Nutella to accumulate levels that may confer a small risk. In other words, it highly unlikely that Nutella increases your risk for cancer.
Figure 1. Nutella, a very tasty chocolate spread.

Figure 2. Glycidol: the epoxide group (three-atom cyclic triangle at the left) is capable of alkylating DNA.

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