dietMet, diet Methionine-Restricted Diet: Click to Expand ⟱
Features:
Methionine (MET) restriction (MR) has been shown to arrest cancer growth and sensitizes tumors to chemotherapy.
-Many cancer cells rely heavily on exogenous methionine to sustain rapid growth and proliferation because they often have impaired methionine salvage pathways.
-Methionine contributes to the synthesis of glutathione, a key antioxidant. (Methionine is a precursor of glutathione, a tripeptide that reduces reactive oxygen species.)
-MR diets might influence the redox state of cancer cells, increasing oxidative stress and thereby leading to cell death in metabolically compromised tumor cells.
-Proliferation and growth of several types of cancer cells are inhibited by MR, while normal cells are unaffected by limiting methionine as long as homocysteine is present.
-Methionine restriction is effective when the non-essential amino acid, cysteine, is absent from the diet or media. methionine is the precursor for cysteine which is essential for the formation of GSH.
-Malignant cells lack the enzyme required to recycle homocysteine therefore giving methionine restriction the capacity to alter cancer cells while maintaining normal, healthy cells.

While vegan diets are typically low in methionine, some nuts and legumes (such as Brazil nuts and kidney beans) are rich in methionine.

Foods to avoid for MR diet:
Animal Proteins:
-Red Meat (Beef, Pork, Lamb):
-Poultry (Chicken, Turkey):
-Fish and Seafood:
-Eggs: Both the egg whites and yolks are protein rich.
-Dairy Products: Milk, cheese, and yogurt
Certain Plant Proteins:
-Soy Products:
-Legumes:
Protein Supplements:

Foods Lower in Methionine (Often Favorable on an MR Diet)
Fruits & Vegetables: leafy greens, berries, apples, and citrus fruits.
Grains & Cereals: rice, oats, and barley
Nuts and Seeds: can vary in methionine content.
Alternative Protein Sources: emphasize protein sources with a lower methionine-to-cysteine ratio.


Scientific Papers found: Click to Expand⟱
2265- dietMet,    Cysteine supplementation reverses methionine restriction effects on rat adiposity: significance of stearoyl-coenzyme A desaturase
- in-vivo, Nor, NA
*SCD1↓, Dietary methionine restriction in rats decreases hepatic Scd1 mRNA and protein,
*Weight↓, MR markedly lowered weight gain, as previously reported (21, 22, 28), despite food intake/g body weight being consistently higher than CF group throughout the study
*Insulin↓, MR significantly decreased serum concentrations of insulin, leptin, IGF-1, and raised adiponectin compared with CF.
*IGF-1↓,
*adiP↑,
*eff↓, these effects were reversed by cysteine

2273- dietMet,    Methionine and cystine double deprivation stress suppresses glioma proliferation via inducing ROS/autophagy
- in-vitro, GBM, U87MG - in-vitro, GBM, U251 - in-vivo, NA, NA
ROS↑, Met-Cys double deprivation had synergistic action on elevating ROS level, decreased GSH level and inhibition of glioma cell proliferation.
GSH↓,
TumCP↓,
TumAuto↑, triggered autophagy of glioma cells both in vitro and in vivo
LC3II↑, Met-Cys deprivation strongly gave rise to the formation of the autophagosome and increased LC3-II protein expression, both of which are autophagy related indicators

2272- dietMet,    Methionine restriction - Association with redox homeostasis and implications on aging and diseases
- Review, Nor, NA
*OS↑, MR seems to be an approach to prolong lifespan which has been validated extensively in various animal models
*mt-ROS↓, Mitochondrial ROS reduction by methionine restriction (MR) maintains redox balance
*H2S↑, MR ameliorates oxidative stress by autophagy activation and hepatic H2S generation.
*FGF21↑, MR impact on cognition by upregulation of FGF21 and alterations of gut microbiome.
*cognitive↑,
*GutMicro↑,
*IGF-1↓, long-term, low-fat, whole-food vegan diet may increase life expectancy in humans by down-regulating IGF-I activity
*mTOR↓, Suppression of the mTOR pathway by MR can also lead to increased H2S production,
*GSH↑, 80% MR increases the GSH content in erythrocytes of rats,
*SOD↑, A diet restricting methionine to 80% (0.17% Met) significantly increases plasma SOD and decreases MDA levels while increasing mRNA expression of Nrf2, HO-1, and NQO-1 in the heart of HFD-fed mice with cardiovascular impairment
*MDA↓,
*NRF2↑,
*HO-1↑,
*NQO1↑,
*GLUT4↑, In skeletal muscle, MR improved expression and transport of GLUT4 and glycogen levels and increased the expression of glycolysis-related genes (HK2, PFK, PKM) in HFD-fed mice
*Glycolysis↑,
*HK2↑,
*PFK↑,
*PKM2↑,
*GlucoseCon↑, promoting glucose uptake and glycogen synthesis, glycolysis, and aerobic oxidation in skeletal muscle.
*ATF4↑, MR can increase the expression of hepatic FGF21 by activating GCN2/ATF4/PPARα signaling in liver cells, thereby improving insulin sensitivity, accelerating energy expenditure, and promoting fat oxidation and glucose metabolism
*PPARα↑,
GSH↓, MR was able to decrease GSH in HepG2 cells, thereby regulating the activation state of protein tyrosine phosphatases such as PTEN.
GSTs↑, decrease of GSH by MR also triggers upregulation of glutathione S-transferase
ROS↑, Double deprivation of methionine and cystine both in vitro and in vivo resulted in a decrease in GSH content, an increase in ROS levels, and an induction of autophagy in glioma cells
*neuroP↑, A neuroprotective role of FGF21

2271- dietMet,    A review of methionine dependency and the role of methionine restriction in cancer growth control and life-span extension
- Review, Nor, NA
*eff↑, The development of methioninase which depletes circulating levels of methionine may be another useful strategy in limiting cancer growth.
*OS↓, methionine restricted diet have reported inhibition of cancer growth and extension of a healthy life-span.
*ROS↓, 40% dietary methionine restriction in male Wistar rats decreases production of ROS in the brain and kidney mitochondria without inhibition of body weight gain which may occur at 80% dietary methionine restriction
*Weight↓, These data suggest that methionine restriction in humans is relatively safe and tolerable over a period of 18 weeks, but the consequences of further weight loss in such cancer patients have not been explored

2270- dietMet,    Methionine-restricted diet inhibits growth of MCF10AT1-derived mammary tumors by increasing cell cycle inhibitors in athymic nude mice
- in-vivo, Var, NA
Weight↓, Mice on the MR diet had reduced body weight and decreased adiposity
TumVol↓, They also had smaller tumors when compared to the mice bearing tumors on the CF diet
P21↑, Elevated expression of P21 occurred in both MCF10AT1-derived tumor tissue and endogenously in mammary gland tissue of MR mice.
p27↑, Breast cancer cell lines MCF10A and MDA-MB-231 grown in methionine-restricted cysteine-depleted media for 24 h also up-regulated P21 and P27 gene expression
*adiP↑, In rodents, a diet low in methionine (20-35 % of regular chow) reduced adiposity in the fat depots and reduced blood levels of lipids, glucose, IGF-1, and leptin, while elevating levels of FGF21 and adiponectin
*glucose↓,
*IGF-1↓,
*FGF21↑,
*OS↑, MR in rodents promotes longevity and delays onset of age-related impairments and chronic diseases
Ki-67↓, number of Ki67-positive stained cells was reduced in the tissue from mice on the MR diet
Casp3↑, MR mice had significantly elevated levels of activated caspase-3
cycD1↓, Methionine restriction increases cell cycle inhibitors P21 and P27, while decreasing cyclin D1

2269- dietMet,    Mechanisms of Increased In Vivo Insulin Sensitivity by Dietary Methionine Restriction in Mice
- in-vivo, Nor, NA
*adiP↑, metabolic responses include reduced adiposity, reduced circulating and tissue lipid levels, increased plasma adiponectin and fibroblast growth factor 21 (FGF-21), and reduced fasting insulin and blood glucose
*FGF↑,
*Insulin↓,
*glucose↓,
Akt↑, activation of Akt was significantly higher in methionine-restricted HepG2 cells
*GSH↓, MR produces a significant decrease in hepatic GSH
PTEN↓, MR in HepG2 cells limits the capacity of the cells to reactivate oxidized PTEN, resulting in amplification of insulin activation of Akt by increasing PIP3.
FGF21↑, MR produced a threefold increase in FGF-21 mRNA that was mirrored by a fourfold increase in serum FGF-21.
PIP3↑,

2268- dietMet,    Methionine dependency and cancer treatment
- Review, Var, NA
ChemoSen↑, last three decades suggest that methionine restriction can become an additional cancer therapeutic strategy, notably in association with chemotherapy.
*eff↑, All normal human cell lines tested in culture, including fibroblasts and liver, kidney and epithelial cells, are methionine-independent
selectivity↑, Numerous malignant cell lines (breast, lung, colon, kidney, bladder, melanoma, glioblastoma, etc.) are methionine-dependent
eff↑, reclinical studies showed better antitumour activity using methionine-free diet plus 5-FU than either treatment administered separately

2267- dietMet,    Role of amino acids in regulation of ROS balance in cancer
- Review, Var, NA
TumCG↓, Indeed, restriction of methionine, which is an essential amino-acid, decreases tumor-growth in patient-derived xenograft mouse models of colorectal cancer by affecting the 1-C metabolism.
GSH↓, Interestingly, methionine restriction leads to a decrease in GSH pool and consequently to a ROS imbalance that affects tumor cell proliferation and can be alleviated by antioxidant treatment.
ROS↑,

2266- dietMet,    Cysteine dietary supplementation reverses the decrease in mitochondrial ROS production at complex I induced by methionine restriction
- in-vivo, Nor, NA
*ROS↓, decrease in mitochondrial ROS generation induced by methionine restriction at complex I
eff↓, results obtained in liver showed that cysteine supplementation reverses the decrease in mitochondrial ROS generation induced by methionine restriction

1893- dietMet,    Clinical Studies of Methionine-Restricted Diets for Cancer Patients
- Review, Var, NA
TumCG↓, Methionine (MET) restriction (MR) has been shown to arrest cancer growth and sensitizes tumors to chemotherapy
ChemoSen↑,
MATs↓, Plasma methionine levels fell from 21.6 to 9 μm within 2 weeks, a 58% decline.

2264- dietMet,    Methionine restriction for cancer therapy: From preclinical studies to clinical trials
- Review, Var, NA
TumCP↓, methionine restriction (MR) reduces cancer cell proliferation via different mechanisms
*ROS?, MR lowers sulfur-containing metabolite levels, reduces oxidative stress, and enhances the immune response
ChemoSen↑, may sensitize tumors to chemo/radiotherapy
RadioS↑,
eff↑, therapeutic potential of MR lies in its ability to synergize with other therapies, enhancing overall antitumor efficacy.
ROS↑, increases ROS, weaking cancer cell defense (from graphical abstract). In colon cancer, MR increases oxidative stress, induces cell cycle arrest, and promotes the apoptosis of p53(Tumor Protein 53)-deleted cells
selectivity↑, methionine-depleted media significantly impaired the growth of malignant cells while leaving normal cell growth unchanged.
TS↓, MR also targets thymidylate synthase (TS), a key enzyme in nucleotide synthesis, enhancing the chemotherapeutic efficacy of 5-FU by lowering TS activity and expression
eff↑, duration of methionine deprivation can significantly affect the tumor cell response. Intermittent methionine deprivation appears particularly beneficial, enhancing tumor cell sensitivity to CD8+ T cell-mediated cytotoxicity

2263- dietMet,    Methionine Restriction and Cancer Biology
- Review, Var, NA
AntiCan↑, dependence of many tumor cells on an exogenous source of the sulfur amino acid, methionine, [9,10,11] makes dietary methionine restriction (MR) an exciting potential tool in the treatment of cancer.
TumCP↓, Proliferation and growth of several types of cancer cells are inhibited by MR,
TumCG↓,
selectivity↑, while normal cells are unaffected by limiting methionine as long as homocysteine is present
ChemoSen↓, MR has been shown to enhance efficacy of chemotherapy and radiation therapy in animal models
RadioS↑,
Insulin↓, MR may work by inhibiting prostate cancer cell proliferation, inhibiting the insulin/IGF-1 axis
*GlucoseCon↑, increase in tissue-specific glucose uptake measured during a hyperinsulinemic-euglycemic clamp
*ROS↓, MR does not increase oxidative stress, in part because MR enhances antioxidant capacity and increases proton leak in the liver, likely decreasing ROS production
*antiOx↑,
*GSH↑, ability of MR to increase GSH levels in red blood cells. Surprisingly, when methionine was restricted by 80% in the diet of rats, the level of GSH in the blood actually increased due to adaptations in sulfur-amino acid metabolism
GSH↑, However, GSH concentrations were reduced in the liver
eff↑, Of note, methionine restriction is effective when the non-essential amino acid, cysteine, is absent from the diet or media.
polyA↓, MR may work by inhibiting prostate cancer cell proliferation, inhibiting the insulin/IGF-1 axis, or by reducing polyamine synthesis. MR-induced depletion of polyamines
TS↓, MR selectively reduces TS activity in prostate cancer cells by ~80% within 48 h, but does not affect TS activity in normal prostate epithelial cells
Raf↓, MR inhibits Raf and Akt oncogenic pathways, while increasing caspase-9 and the mitochondrial pro-apoptotic protein, Bak
Akt↓,
Casp9↑,
Bak↑,
P21↑, MR upregulating p21 and p27 (cell cycle inhibitors that halt cell cycle progression) in LNCaP cells
p27↑,
Insulin↓, MR-induced reduction in circulating insulin and IGF1, which have both been linked to tumor growth
IGF-1↓,

2170- dietMet,    Low Protein Intake is Associated with a Major Reduction in IGF-1, Cancer, and Overall Mortality in the 65 and Younger but Not Older Population
- Study, Var, NA
OS↑, Respondents (n=6,381) aged 50–65 reporting high protein intake had a 75% increase in overall mortality and a 4-fold increase in cancer and diabetes mortality during an 18 year follow up period. (higher OS for low protein)
eff↝, Conversely, in respondents over age 65, high protein intake was associated with reduced cancer and overall mortality.
other↝, Mouse studies confirmed the effect of high protein intake and the GHR-IGF-1 axis on the incidence and progression of breast and melanoma tumors, and also the detrimental effects of a low protein diet in the very old.

1897- dietMet,    Methionine metabolism in health and cancer: a nexus of diet and precision medicine
- Review, Var, NA
OS↑, dietary MR, which reduces but does not completely eliminate methionine, and improvement of health as well as reversal of pathology, by means including lifespan extension, attenuation of high fat diet-induced obesity and prevention of diabetes
TumCG↓, where animals were fed diets lacking individual amino acids and were subsequently shown to exhibit significantly reduced tumour growth under a methionine-deprived diet
TumCCA↑, MR was shown to effectively induce a cell cycle blockade and overall tumour regression
ChemoSen↑, MR significantly increased the efficacy of 5-FU treatment when 5-FU was given at a chemoresistant dose
RadioS↑, MR also showed synergistic effects when combined with radiation, which as a monotherapy had previously been shown to exert only a modest effect

1896- dietMet,    Dietary methionine links nutrition and metabolism to the efficacy of cancer therapies
- in-vivo, CRC, NA
TumCG↓, Dietary MR rapidly and specifically alters methionine and sulfur metabolism and inhibits tumour growth in colorectal patient-derived xenograft (PDX) models
*GSH↓, MR reduced NAC and glutathione in all subjects
RadioS↑, Strikingly, MR with a focal dose of 20 Gy reduced tumour growth
eff↑, MR synergized with 5-FU treatment, leading to a marked inhibition on tumour growth

1895- dietMet,    Altering Diet Enhances Response to Cancer Treatments in Mice
- Review, Var, NA
ChemoSen↑, diet very low in the nutrient methionine improved the ability of chemotherapy and radiation therapy to shrink tumors.

1894- dietMet,    Long term methionine restriction: Influence on gut microbiome and metabolic characteristics
- in-vivo, Nor, NA
*GutMicro↓, pecific taxa changes due to the diet were observed at the 1 or 18‐week time points, including Ileibacterium, Odoribacter, Lachnoclostridium, Marinifilaceae, and Lactobacillaceae.
*OS↑, MR diet feeding was also found to boost healthspan and lifespan in progeroid mice
Weight↓, This reduction in body weight coincided with reductions in BMD and percent fat mass, and an increase in percent lean mass
BG↓, MR mice had significantly reduced blood glucose levels at all time points except at 5 and 15 min indicating an increase in insulin sensitivity


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 17

Results for Effect on Cancer/Diseased Cells:
Akt↓,1,   Akt↑,1,   AntiCan↑,1,   Bak↑,1,   BG↓,1,   Casp3↑,1,   Casp9↑,1,   ChemoSen↓,1,   ChemoSen↑,5,   cycD1↓,1,   eff↓,1,   eff↑,5,   eff↝,1,   FGF21↑,1,   GSH↓,3,   GSH↑,1,   GSTs↑,1,   IGF-1↓,1,   Insulin↓,2,   Ki-67↓,1,   LC3II↑,1,   MATs↓,1,   OS↑,2,   other↝,1,   P21↑,2,   p27↑,2,   PIP3↑,1,   polyA↓,1,   PTEN↓,1,   RadioS↑,4,   Raf↓,1,   ROS↑,4,   selectivity↑,3,   TS↓,2,   TumAuto↑,1,   TumCCA↑,1,   TumCG↓,5,   TumCP↓,3,   TumVol↓,1,   Weight↓,2,  
Total Targets: 40

Results for Effect on Normal Cells:
adiP↑,3,   antiOx↑,1,   ATF4↑,1,   cognitive↑,1,   eff↓,1,   eff↑,2,   FGF↑,1,   FGF21↑,2,   glucose↓,2,   GlucoseCon↑,2,   GLUT4↑,1,   Glycolysis↑,1,   GSH↓,2,   GSH↑,2,   GutMicro↓,1,   GutMicro↑,1,   H2S↑,1,   HK2↑,1,   HO-1↑,1,   IGF-1↓,3,   Insulin↓,2,   MDA↓,1,   mTOR↓,1,   neuroP↑,1,   NQO1↑,1,   NRF2↑,1,   OS↓,1,   OS↑,3,   PFK↑,1,   PKM2↑,1,   PPARα↑,1,   ROS?,1,   ROS↓,3,   mt-ROS↓,1,   SCD1↓,1,   SOD↑,1,   Weight↓,2,  
Total Targets: 37

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