Mutant Vegetarians?

"Study finds that Vegetarians are Mutant"¹
"Vegetarian Diet May Alter Human DNA, Raising Cancer, Hesart Disease Risks"²
"Being a Vegetarian Could Kill You, Science Warns."³

These sensational headlines are based on new research published for advanced access in the journal Molecular Biology and Evolution by a research group from Cornell University.⁴ As a molecular biologist and nutrition researcher, I was skeptical about these claims and was eager to learn more about the study. What I found was a fantastic study with exciting findings in need of no embellishment.

This new research focused on the omega-6 polyunsaturated fatty acid, arachidonic acid. Arachidonic acid plays many roles in the human body and is a main constituent of cell membranes. Dietary sources of arachidonic acid include meat, fish, poultry, and eggs. Unlike most omega-6 fatty acids, which are usually consumed in our diet as vegetable oils, arachidonic acid is not found in plants. However, humans are able to convert a precursor found in plants, another omega-6 fatty acid, known as linoleic acid, into arachidonic acid. In their study, Kumar Kothapalli and his colleagues at Cornell University found that some people are more efficient at this conversion than others.⁴

The reason: Genetics

To gain a better understanding of the findings of this research, I spoke directly with Dr. Kothapalli. According to Kothapalli, the study demonstrated that a population which has been practicing vegetarianism for many generations actively produces more of a particular enzyme known as fatty acid desaturase, which is responsible for converting linoleic acid to arachidonic acid.

Initially, the researchers found different versions of the fatty acid desaturase gene in a Japanese population. In some people they found a small section of DNA to be deleted in this gene. Since we have two copies of each gene, this allows for 3 different variations; those with both copies intact (I/I), those which have one copy with the section deleted (I/D) and those which have both copies with the section deleted (D/D). They found those with both copies intact (I/I) had significantly higher amounts of fatty acid desaturase, indicating they would be more efficient at converting the plant-based linoleic acid to arachidonic acid than those with both sections of the gene deleted (D/D).⁴

Kothapalli and his colleagues then determined how often each variation occurs using human DNA samples. The DNA samples were taken from a population in Pune, India who are primarily vegetarian and have been vegetarian for many generations. Their DNA samples were compared with samples from the United States. The analysis found the I/I variation occurred in 68% of the Indian population and only in 18% of the United States population.⁴ The researchers then used global genetic data to determine how frequently the variants occur worldwide. Globally, the I/I variation was found in 70% of South Asians, 53% of Africans, 29% of East Asians, and 17% of Europeans.⁴

To confirm that the I/I variation did in fact lead to increased conversion of linoleic acid to arachidonic acid, the researchers performed biochemical tests on human samples. As they predicted, arachidonic acid levels were 8% higher in I/I individuals than D/D.⁴ The activity of the enzyme was also shown to be higher in the I/I group, with 31% greater conversion of linoleic to arachidonic acid than the D/D group.⁴

Overall, what this study truly shows is that over generations, populations who eat predominantly vegetarian diets (that usually include dairy products but not eggs) have adapted to low intakes of arachidonic acid by becoming more efficient at producing arachidonic acid. So, why did these results garner the sensational headlines?

To understand this, we need to take a look at the current hypothesis of how different types of unsaturated fats affect our health. The best model we have today is the omega-6 to omega-3 ratio. This ratio is used to compare the balance of different types of unsaturated fats in our diets.

According to some, the types of fats we eat have changed dramatically over the past 150 years. These researchers believe humans evolved eating foods such as lean meats, fish, fruits, vegetables, and nuts, resulting in a dietary fatty acid ratio of 1:1 omega-6 to omega-3.⁵ Today the intake ratio for the general population has tilted heavily in favor of omega-6 fatty acids to 15:1.⁵ This is largely due to the increased availability of seed oils such as soy, corn, and cottonseed and inexpensive grain-fed meats. For vegetarians and vegans this ratio may be even higher because their diets often contain few omega-3 fatty acids. For example, the omega-3 fatty acids DHA and EPA are mainly found in cold-water fatty fish.

The relatively higher intake of omega-6 fatty acids is believed by some researchers to result in inflammation and pro-inflammatory diseases like heart disease and colon cancer.^6,7 The science on omega-3 fatty acids seems to be pretty clear; they are anti-inflammatory. However, when it comes to the omega-6 fatty acids, specifically arachidonic acid, the science appears to be more complicated. Arachidonic acid itself is a precursor to both pro-inflammatory and anti-inflammatory molecules.⁸ This connection between omega-6 fatty acids and pro-inflammatory diseases misled some journalists to believe higher arachidonic acid production in those with the I/I variation would put them be at higher risk for those diseases. In reality, vegetarians tend to have lower risks for these chronic diseases.⁹

For now, the hypothesis that the dietary omega-6 to omega-3 ratio is relevant for health seems to fall into the realm of expert opinion rather than that of sound scientific findings. Historical fatty acid ratio findings are based on extrapolations from a handful of anthropological nutrition studies and observations on wild animals. The data suggesting a high omega-6 to omega-3 ratio is harmful come from small studies with few participants, cell culture studies, and epidemiological observations.

Skepticism surrounding these findings seems justified when considering the breadth of data suggesting omega-6 intake is associated with decreased risk of heart disease. Over the past few decades, randomized trials, case-control and cohort studies, and long-term animal feeding experiments have all demonstrated a decreased risk of heart disease for those eating 5-10% of calories from omega-6 fatty acids when compared to eating lower amounts.¹⁰ In line with these findings, a 2009 science advisory from the American Heart Association, "recommends that people aim for at least 5 percent to 10 percent of calories from omega-6 fatty acids."¹⁰

Kothapalli, however, is a firm believer in the omega-6 to omega-3 ratio hypothesis. When asked about the implication of the study for those eating a vegetarian diet he responded: "If they are eating a vegetarian diet they should balance the omega-3s and omega-6s in their diet. Don't eat more omega-6 from…vegetable oils. They need to balance between omega-6 and omega-3, then they will be okay."

To gain a better perspective on the extensive amount of variable findings, I met with the leading expert on all things fat-related, Dr. Eric Decker, Head of the Department of Food Science at the University of Massachusetts, Amherst. His answer was rather simple: the data are largely incon-clusive with the exception that the general population is not currently consuming enough long chain omega-3 fatty acids on average here in the United States. Regardless who you are, vegetarian, vegan, omnivore, you should be eating more long chain omega-3s.

The U.S. Dietary Guidelines suggest consuming the equivalent amount of DHA and EPA from 2 servings of fatty fish per week, which works out to be about 250 milligrams of EPA and DHA per day.¹¹ On average, Americans consume 63 mg of DHA and 23 mg of EPA per day.¹² In vegetarians and vegans, these intake levels are even lower and sometimes even nonexistent. Vegan dietary sources of DHA and EPA are limited to sea vegetables, fortified foods, and supplements. Microalgae-derived DHA is vegan and widely available in supplement form. Sea vegetables have been growing in popularity in recent years as they are sustainable and provide EPA. A list of DHA and EPA sources can be found in the chart below.

Source: Sanchez-Machado DI, Lopez-Hernandez J, Paseiro-Losada P, Lopez-Cervantes J. Fatty acids, total lipid, protein and ash contents of processed edible seaweeds. Food Chem. 2004;85:439-444 and manufacturers' information.

Unfortunately, as with most nutrition-related inquiries, there is no definitive answer as of yet. The beauty of this study is that it brings us one step closer to better answers. As of now, we are reliant on unreliable data for our information. With the advent of the fields of nutrigenetics (the study of the effects of dietary patterns on genetics over time) and nutrigenomics (the study of the effects of nutrient intake on gene expression), we are becoming ever closer to making personalized dietary recommendations.