Asparagine and triple negative breast cancer

Feb 25, 2018

A new study published the first week of February in the journal Nature is making waves. Simon Knott et al published evidence that the amino acid arginine plays a critical role in the metastatic spread of triple negative breast cancer (TNBC). [1]

This is really big news. “Triple negative breast cancers (TNBC), comprise 15-20% of breast cancers, and are associated with later stage at diagnosis, increased mortality, and occur more frequently in younger women where mammographic screening is less reliable. TNBCs are more likely to be diagnosed by physical exam than by mammographic screening.” [2] In TNBC when tumor samples are tested in the laboratory they are “… negative for estrogen receptors (ER-), progesterone receptors (PR-), and HER2 (HER2-). Testing negative for all three means the cancer is triple-negative.

These negative results mean that the growth of the cancer is not encouraged by estrogen, nor by the presence of too many HER2 receptors. Therefore, triple-negative breast cancer does not respond to hormonal therapy (such as tamoxifen or aromatase inhibitors) or therapies that target HER2 receptors, such as Herceptin (chemical name: trastuzumab). [3]

This single amino acid building block may “hold a key to preventing the spread of” TNBC according to this new study.

By limiting asparagine in laboratory mice with triple-negative breast cancer, the researchers dramatically reduced the ability of the cancer to travel to distant sites in the body. Among other techniques, the team used dietary restrictions to limit asparagine.

Foods rich in asparagine include dairy, whey, beef, poultry, eggs, fish, seafood, asparagus, potatoes, legumes, nuts, seeds, soy and whole grains. Foods low in asparagine include most fruits and vegetables. At least that’s what has been appearing in the news articles. Finding specific quantities found per food serving has been challenging as this has not been on anyone’s radar up until now.

Asparagine plays an important role in nitrogen storage and transport in many plants as it has a high ratio of nitrogen to carbon and is relatively non reactive. It accumulates in its free form during seed germination and in response to stressors. It has become relevant in recent years because it is essential in the chemical reaction that produces the carcinogen acrylamide in high temperature cooking of foods.

For acrylamide to form in food requires a number of factors to be present including high asparagine content, high carbohydrates, specific reducing sugars, specifc pH levels, water content and ammonium bicarbonate to all be present, and then exposure high temperatures (>120°C). Keep in mind though that high asparagine foods, lacking these other requisites are not necessarily going to contain acrylamide.[4] Remember that French Fries were one of the biggest acrylamide forming foods.

If this sounds confusing, we aren’t finished yet. Asparagine will vary in plants with adequacy or deficiency of certain minerals in the soil. For example sulfur deficiency in the soil will boost asparagine formation in grains.[5] Perhaps this is why it is so difficult to find a list of asparagine in foods. It may vary by too much.

There are some obvious questions that you are probably wondering about that we do not have answers to yet:
1. What about double negative?
2. What about ER +?
3. What about the drug l-asparginase that deplets asparagine in the body?
4. A friend told me to eat asparagus daily to cure my cancer…. What about that?

[Well we do know about that myth as we posted a response back in 2011:


1. Nature. 2018 Feb 7. doi: 10.1038/nature25465. [Epub ahead of print]
Asparagine bioavailability governs metastasis in a model of breast cancer.
Knott SRV1,2,3, Wagenblast E2,4,5, Khan S2,6, Kim SY2, Soto M2, Wagner M7, Turgeon MO7, Fish L8,9,10, Erard N1, Gable AL2, Maceli AR2, Dickopf S2, Papachristou EK1, D’Santos CS1, Carey LA11, Wilkinson JE12, Harrell JC13, Perou CM14, Goodarzi H8,9,10, Poulogiannis G7,15, Hannon GJ1,2,6.
PMID: 29414946 DOI: 10.1038/nature25465