Controlled Amino Acid Therapy and Cancer
In vitro and in vivo data suggest that selective amino acid deprivation may have anticancer activity.
Controlled amino acid therapy (CAAT) is a protocol developed for patients with cancer that includes strict dietary guidelines and nutritional supplements that focus on controlling amino acid and carbohydrate intake.1,2
The protocol was developed by the A.P. John Institute for Cancer Research and is touted to be based on extensive clinical research, but studies in humans or animal models of the entire CAAT protocol have not been published, nor have results — case studies or observational studies — from the institute been published. The exact protocol is not reported and the website for the institute is no longer functioning.
Components of the protocol, such as selective amino acid restriction, and supplements such as vitamin D and antioxidants, have been studied separately in vitro and in some animal models. This fact sheet focuses on the amino acid deprivation component.
Selective Amino Acid Deprivation
A major component of CAAT is selective amino acid restriction therapy (SAART), which is based on the hypothesis that many cancer cells develop mutations that prevent the synthesis of some amino acids that are required for protein synthesis and thus continued cell survival. When these cancer cells are deprived of an exogenous source of these amino acids, the cell cannot perform protein synthesis and thus is unable to survive.3
It has sbeen proposed that temporary selective deprivation of amino acids may result in the death of cancer cells without affecting normal cells or causing muscle proteolysis. This hypothesis has not, however, been fully tested in vivo, but is based on observations from studies of single amino acid deprivation and overall protein restriction in vitro and in vivo.
Findings from one study suggest that a substantial decrease in overall protein intake inhibits cell proliferation in castration-resistant prostate cancer cells and amino acid starvation culture conditions (ie, amino acids not present in culture medium) combined with gefitinib resulted in cytotoxicity of EGFR-expressing cancer cell lines.4,5
Decreased protein intake also inhibited tumor growth, but did not affect body weight, in a xenograft mouse model of human breast cancer.4 Several studies also suggest that selective amino acid deprivation of serine and glycine or phenylalanine and tyrosine can inhibit tumor growth in animal models.6,7
Many internet sites claim that CAAT has been studied in clinical trials. These trials, however, evaluated only the amino acid deprivation portion of the protocol and only in very small, single-arm studies. One study conducted in the 1960s, for example, evaluated 5 patients with metastatic melanoma who consumed a diet restricted in phenylalanine and tyrosine.8 Tumor growth was measured by calipers and lung metastases were monitored by X-ray. Four of the patients experienced slowed tumor growth, which also correlated with lower levels of serum phenylalanine and tyrosine. The authors concluded that the diet appeared to inhibit tumor growth, but was difficult for patients to follow.