Methionine Dependent Cancers

Homocysteine is a non-protein amino acid. It is synthesized in the body from methionine, which is a sulfur containing amino-acid. Methionine is much more prevalent in animal products than plant products. Rotten eggs smell the way they do because the sulfur produces a number of sulfur containing gasses including hydrogen sulfide— rotten egg gas.

A high level is of homocysteine is associated with an increased risk for chronic inflammation, cardiovascular disease, and Alzheimer’s disease. 1 2 Many human cancer cell and primary tumors have a requirement for methionine, an essential amino acid. 3

Methionine-free or methionine-deprived diet causes a regression of a variety of animal tumours.

A methionine restricted diet have shown inhibition of cancer growth and extension of a healthy life-span in animal studies. In humans, vegan diets, low in methionine, may prove to be a useful nutritional strategy in cancer growth control. 4

In 1974, a paper originating from the University of California opened with the following paragraph.

In tissue cultures of normal adult and malignant mammalian cells, homocystine has been substituted for methionine in a medium rich in folic acid and cyanocobalamin. Normal adult cells thrive. Three highly malignant cell types from three different species, including man, die. 5

The paper continued with,

In several lines of malignant cells we have observed an inability of the cells to survive and grow when methionine is replaced in the medium with homocystine. However, normal adult cell lines derived from mice, rats, and humans survive and grow well with this substitution. The apparent absolute dependence of the malignant cells on preformed methionine is of considerable theoretical interest but may also be of practical importance because it may offer another avenue for treating neoplastic disease.

This concept has not received the attention that it deserves, even though some forty years later two studies still considered the concept viable.

The first paper originated from CSIRO Food and Nutritional Sciences in Adelaide, Australia.

Methionine is an essential amino acid with many key roles in mammalian metabolism such as protein synthesis, methylation of DNA and polyamine synthesis. Restriction of methionine may be an important strategy in cancer growth control particularly in cancers that exhibit dependence on methionine for survival and proliferation. 6

A common feature of some cancers is the absolute requirement for methionine, a phenomenon known as ‘methionine dependence’. Therefore, restriction of methionine may be a useful strategy in limiting cancer growth. Methionine restriction may also prolong a healthy life-span.

The second paper 2012 agrees, stating,

Restriction of methionine may be an important strategy in cancer growth control particularly in cancers that exhibit dependence on methionine for survival and proliferation. 7
Since animal foods contain about four times as much methionine compared with plant-based foods, the best way to restrict methionine is to consume a plant-based diet.

Reference range for homocysteine is less than 12 µmol / L. An optimal level is probably 8 µmol / L or less.

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Footnotes

  1. Richmann, E. L., Kenfield, S. A., Stampfer, M. J., Giovannucci, E. L., Zeisel, S. H., Willett, W. C., & Chan, J. M. (2012). Choline intake and risk of lethal prostate cancer: Incidence and survival. American Journal of Clinical Nutrition, 96(4), 855–863.
  2. Romano, K. A., Vivas, E. I., Amador-Noguez, D., & Rey, F. E. (2015). Intestinal Microbiota Composition Modulates Choline Bioavailability from Diet and Accumulation of the Proatherogenic Metabolite Trimethylamine- N -Oxide. MBio, 6(2), e02481-14.
  3. Cellarier, E., Durando, X., Vasson, M., Farges, M., Demiden, A., Maurizis, J., Madelmont, J., & Chollet, P. (2003). Methionine dependency and cancer treatment. Cancer Treatment Reviews, 29 (6), 489–499.
  4. Cavuoto, P., & Fenech, M. F. (2012). A review of methionine dependency and the role of methionine restriction in cancer growth control and life-span extension. Cancer Treatment Review, 38(6), 726–736.
  5. Halpern, B. C., Clark, B. R., Hardy, D. N., Halpern, R. M., & Smith, R. A. (1974). The Effect of Replacement of Methionine by Homocystine on Survival of Malignant and Normal Adult Mammalian Cells in Culture. Proceedings of the National Academy of Sciences, 71(4), 1133–1136.
  6. Cavuoto, P., & Fenech, M. F. (2012). A review of methionine dependency and the role of methionine restriction in cancer growth control and life-span extension. Cancer Treatment Reviews, 38(6), 726–736.
  7. Agrawal, V., Alpini, S. E., Stone, E. M., Frenkel, E. P., & Frankel, A. E. (2012). Targeting methionine auxotrophy in cancer: Discovery & exploration. Expert Opinion on Biological Therapy, 12(1), 53–61.

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