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For every plus there is a minus: A review of methionine dependency and the role of methionine restriction in cancer growth control and life-span extension htt

For every plus there is a minus: A review of methionine dependency and the role of methionine restriction in cancer growth control and life-span extension http://www.cancertreatmentreviews.com/article/S0305-7372(12)00005-9/abstract http://www.cancertreatmentreviews.com/article/S0305-7372(12)... 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. Methionine dependence in cancer may be due to one or a combination of deletions, polymorphisms or alterations in expression of genes in the methionine de novo and salvage pathways. Cancer cells with these defects are unable to regenerate methionine via these pathways. Defects in the metabolism of folate may also contribute to the methionine dependence phenotype in cancer. Selective killing of methionine dependent cancer cells in co-culture with normal cells has been demonstrated using culture media deficient in methionine. Several animal studies utilizing a methionine restricted diet have reported inhibition of cancer growth and extension of a healthy life-span. In humans, vegan diets, which can be low in methionine, may prove to be a useful nutritional strategy in cancer growth control. The development of methioninase which depletes circulating levels of methionine may be another useful strategy in limiting cancer growth. The application of nutritional methionine restriction and methioninase in combination with chemotherapeutic regimens is the current focus of clinical studies.

scythe 10y ago
Details, details, details. https://www.researchgate.net/profile/Daniel_Epner/publication/11049822_Nutrient_Intake_and_Nutritional_Indexes_in_Adults_With_Metastatic_Cancer_on_a_Phase_I_Clinical_Trial_of_Dietary_Methionine_Restriction/links/53f1f55b0cf272810e4c7a1a.pdf https://www.researchgate.net/profile/Daniel_Epner/publicatio... > Alternatively, weight loss experienced by patients in the trial may have been independ - ent of energy intake but, rather, attributable to “obligatory” muscle catabolism related to methionine restriction per se. A recent study designed to quantify dietary methionine re - quirements in normal subjects sheds light on this issue (22). In that study, stable isotope methods were used to measure obligatory methionine oxidation in normal subjects on a diet completely devoid of sulfur amino acids (methionine and cysteine) for 5 days. Although somewhat controversial (23), obligatory oxidation rates are considered by many to repre - sent the minimum requirement for amino acids, that is, the amount that is oxidized despite maximal body conservation. The obligatory oxidative loss of methionine was 13 mg/kg/ day in that study (22). Patients in our trial, who were re - stricted to 2 mg methionine/kg/day, therefore, consumed 11 mg/kg/day less than the minimum requirement. However, they consumed adequate amounts of cysteine, which is pres - ent in Hominex-2. They therefore may have had obligatory methionine oxidation rates < 13 mg/kg/day. The fact that all patients reversibly lost weight, despite what would normally be considered adequate energy and protein intake, may actu - ally be encouraging, since it confirms that patients adhered to the diet. The basic premise of this strategy is that dietary methionine restriction will have a greater deleterious effect on tumors than on normal host tissues. Unless you actually have cancer, obligate muscle catabolism secondary to methionine restriction is a high price to pay.

scythe 10y ago

Details, details, details. https://www.researchgate.net/profile/Daniel_Epner/publication/11049822_Nutrient_Intake_and_Nutritional_Indexes_in_Adults_With_Metastatic_Cancer_on_a_Phase_I_Clinical_Trial_of_Dietary_Methionine_Restriction/links/53f1f55b0cf272810e4c7a1a.pdf https://www.researchgate.net/profile/Daniel_Epner/publicatio... > Alternatively, weight loss experienced by patients in the trial may have been independ - ent of energy intake but, rather, attributable to “obligatory” muscle catabolism related to methionine restriction per se. A recent study designed to quantify dietary methionine re - quirements in normal subjects sheds light on this issue (22). In that study, stable isotope methods were used to measure obligatory methionine oxidation in normal subjects on a diet completely devoid of sulfur amino acids (methionine and cysteine) for 5 days. Although somewhat controversial (23), obligatory oxidation rates are considered by many to repre - sent the minimum requirement for amino acids, that is, the amount that is oxidized despite maximal body conservation. The obligatory oxidative loss of methionine was 13 mg/kg/ day in that study (22). Patients in our trial, who were re - stricted to 2 mg methionine/kg/day, therefore, consumed 11 mg/kg/day less than the minimum requirement. However, they consumed adequate amounts of cysteine, which is pres - ent in Hominex-2. They therefore may have had obligatory methionine oxidation rates < 13 mg/kg/day. The fact that all patients reversibly lost weight, despite what would normally be considered adequate energy and protein intake, may actu - ally be encouraging, since it confirms that patients adhered to the diet. The basic premise of this strategy is that dietary methionine restriction will have a greater deleterious effect on tumors than on normal host tissues. Unless you actually have cancer, obligate muscle catabolism secondary to methionine restriction is a high price to pay.