Eating vegetables with fish increases cancer risk.

Zeilmaker MJ, MI Bakker, R Schothorst and W Slob. 2010. Risk assessment of N-nitrosodimethylamine formed endogenously after fish-with-vegetable meals. Toxicological Science http://dx.doi.org/10.1093/toxsci/kfq093.

The risk of liver cancer slightly increases when eating fish together with certain naturally high-nitrate vegetables in the same meal, report researchers in a recent issue of Toxicological Sciences.

The increased risk – though marginal – occurs when substances in the fish and the vegetables form a cancer-causing agent in the acidic environment of the stomach. The chemical is called N-nitrosodimethylamine or NMDA. NMDA is a strong cancer-causing agent in animals and is listed as a probable human carcinogen.  

NMDA can be formed in the stomach under certain conditions. After a nitrate-rich meal, the nitrate is converted to nitrite by bacteria in saliva. After swallowing, the nitrite reacts with components of fish (dimethylamines) to form NMDA in the stomach. This chemical reaction only happens under the acidic conditions of the stomach and stops once the food reaches the intestine.

While the paper did not address whether this same scenario could also happen if an individual consumes nitrate or drinks nitrite-contaminated water, it is not impossible.  Current drinking water standards set by the EPA have limited nitrate-nitrogen content to 10 milligrams per liter and 1 milliliter per liter for public water sources, primarily based on the risks to pregnant women – "blue baby" syndrome can occur at high nitrate-nitrogen exposures that impair the oxygen-carrying ability of the mother's blood.  Nitrate-nitrogen exposure is suspected to be linked to increased risks of cancer in adults, although this varies depending on the type of cancer studied.

Estimating NMDA content following fish-with-vegetable meals is difficult in people. To do so, the authors created a system in which they mimicked the motion of food and the acidic conditions in the stomach. They added different levels of nitrite to examine a broad range of potential exposures. Then, they measured NMDA.

The authors developed a computer model to estimate cancer risk by combining this data with information from published animal and human studies. The cancer risk was increased in rats after both short-term and long-term exposure to the combination of fish and nitrate-rich vegetables, such as spinach, celery, red beets, and Chinese cabbage.

For people, this amounted to a reduced “time-to-cancer” development of nine days. This means that on average, individuals who eat fish-with-nitrate-rich-vegetable meals are more likely to develop cancer earlier than unexposed individuals.  While this reduced cancer-free time is small, the percentage of the population potentially at risk is quite high.

Of the fish tested, cod had the highest production of NMDA. Without other meal components added, approximately 17 micrograms of NMDA was produced from a mix of about 7 ounces of cod with about 5 ounces of spinach. Other foods – such as additional vegetables or starches – reduced this level by 10 fold to just 1.7 micrograms.  Both of these levels (17 and 1.7) are low, but well above the current information available for NMDA toxicity in animals, which lists exposure levels 1,000 times lower, in the nanogram range.

Computer modeling studies like this one use mathematical models and equations to estimate long term outcomes. The authors chose conservative estimates and not only the "worst case scenario" for their model assumptions. The approach adds weight to the findings of the study, and suggests that perhaps potatoes may be a better vegetable to eat with cod.  Overall, this study suggests that chemistry – not solely taste – plays a part in healthy food pairing.