Methionine Restriction: Ready for Prime Time in the Cancer Clinic?

[Daniel E.]

Methionine Restriction: Ready for Prime Time in the Cancer Clinic?

Attempts to selectively starve cancers in the clinic have been made at least since the time of Warburg beginning 100 years ago. Calorie-restriction or low-carbohydrate diets have had limited success with cancer patients. Methionine restriction is another strategy to selectively starve cancer...

ar.iiarjournals.org

JUN YAMAMOTO, QINGHONG HAN, MARK SIMON, DANIEL THOMAS and ROBERT M. HOFFMAN
February 2022

Attempts to selectively starve cancers in the clinic have been made at least since the time of Warburg beginning 100 years ago. Calorie-restriction or low-carbohydrate diets have had limited success with cancer patients. Methionine restriction is another strategy to selectively starve cancer cells, since cancers are addicted to methionine, unlike normal cells.

Methionine addiction of cancer is termed the Hoffman effect. Numerous preclinical studies over the past half century have shown methionine restriction to be highly effective against all major cancer types and synergistic with chemotherapy. Low-methionine medical diets can be effective in lowering methionine and have shown some clinical promise, but they are not palatable and thereby not sustainable. However, selectively choosing among plant-based foods allows a variety of low-methionine diets that are sustainable.

Our laboratory has developed a methioninase that can be administered orally as a supplement and has resulted in anecdotal positive results in patients with advanced cancer, including hormone-independent prostate cancer, and other recalcitrant cancers. The question is whether methionine restriction through a low-methionine diet, or even greater methionine restriction with methioninase in combination with a low-methionine diet, is ready for prime time in the clinic, especially in combination with other synergistic therapy. The question will hopefully be answered in the near future, especially for advanced cancer patients who have failed all standard therapy.

 

[Daniel E.]

Methionine- Restricted Diet… Who needs it? - Brenda Davis RD

Methionine is an essential amino acid — one of the building blocks of protein that cannot be produced by the human body so must come from our food. It is one of two sulfur-containing amino acids (the other is cysteine). Methionine is an intermediary in the synthesis of cysteine, carnitine...

www.brendadavisrd.com

November 2015

Methionine is an essential amino acid — one of the building blocks of protein that cannot be produced by the human body so must come from our food. It is one of two sulfur-containing amino acids (the other is cysteine). Methionine is an intermediary in the synthesis of cysteine, carnitine, taurine, and other compounds. It protects liver cells, and helps to prevent lipid peroxidation, and possibly atherosclerosis and elevated cholesterol. Although methionine is essential to human life, some people benefit by limiting, but not eliminating methionine in their diets. For such individuals a methionine-restricted diet may be advised.

Should I be on a methionine-restricted diet?

Some individuals need to restrict methionine due to inherited disorders that affect methionine metabolism. There is growing interest in methionine restricted diets for those who are unaffected by these genetic metabolic disorders. Evidence suggests that such diets could enhance longevity and help to prevent or treat certain chronic health conditions. The most common indications for a methionine-restricted diet ar

i) MTHFR variants. MTHFR gene mutations can lead to elevated homocysteine. Methionine restriction is commonly recommended to help reduce homocysteine accumulation.

ii) Cancer. While human studies are sparse, there is some evidence that cancer cells grow less robustly, and sometimes undergo apoptosis (cell death) when deprived of methionine

iii) Depression. High methionine intakes can elevate homocysteine levels and risk of depression.

iv) Lifespan extension. Low methionine diets increase metabolic flexibility and overall insulin sensitivity and improve lipid metabolism while decreasing systemic inflammation.

v) Insulin resistance. Methionine restriction has been shown to reduce adiposity and improve insulin sensitivity.

vi) Homocystinuria. This inherited disorder of metabolism often requires a low methionine diet.



If methionine-restriction may help kill cancer cells and increase longevity, shouldn’t everyone be on a methionine-restricted diet?

We don’t know for sure, but it is an option for those who are interested in employing a novel dietary strategy for disease risk reduction. While severe methionine restriction is rarely advised, a moderate methionine restriction may be beneficial. The most concentrated methionine sources are animal products such as meat, poultry and fish. You will see from the table below that the eating pattern that is lowest in methionine is a purely plant-based diet or vegan diet. Other vegetarian or near-vegetarian diets are lower in methionine than omnivores diets, but not as low as vegan diets. For most people, simply eating a plant-based diet is likely sufficient for reducing methionine intake. Those with metabolic disorders or other conditions that may warrant methionine restriction can further restrict methionine by limiting high methionine plant-based foods.



If a methionine restricted diet is indicated for me, how much methionine should I be eating each day?

The RDA (recommended dietary allowance) for methionine + cysteine (adults 19 yrs+) is 19 mg/kg/day, while the EAR (estimated average requirement) is 15 mg/kg/day. People should not dip too much below these levels as they represent the lower end of what is needed for human health. Methionine-restricted diets allow 800-1200 mg methionine per day for most adults. For methionine alone, 15 mg/kg is thought to be a reasonable lower limit. So, if a therapeutic, methionine-restricted diet is indicated for you, multiply your healthy body weight [in kilograms] by 15 to find a level of methionine intake that is appropriate. Let’s say your healthy body weight is 60 kg, you would need 900 mg methionine per day.



Are there any downsides to severely restricting methionine?

Absolutely. There is some evidence that a lack of methionine could reduce levels of S-Adenosylmethionine or SAM-e increasing risk of depression. A lack of methionine has also been linked to senile graying of hair. When you restrict methionine you are naturally restricting protein, at least to some degree. Ensuring sufficient protein is essential to health. Protein is necessary for building, strengthening and repairing body tissues, for making antibodies, hormones, enzymes and other compounds that are critical to every body process. A lack of protein can result in muscle loss, increased risk of bone fractures and undesirable changes in hair and skin. Seniors tend to absorb protein less efficiently, so they may need to consume 15-25% more protein than other adults in order to absorb the same amount. So while methionine restriction can be beneficial, it is important that we meet our needs for methionine, and for protein.

 

[Daniel E.]

Methionine Restriction Increases by 50% Lifespan of Mice with Aggressive Brain Cancer

A new study points to the possibility that dietary modulation could represent a promising treatment approach for an otherwise incurable brain tumor of childhood.

www.genengnews.com

April 2022

“The Achilles’ heel of these tumors is that they are rapidly growing and use a lot of nutrients,” said Sameer Agnihotri, PhD, assistant professor of neurological surgery at Pitt. “Combining metabolic approaches—changes in diet—with next-generation scientific tools might become a way of harnessing our understanding of how nutrient needs of cancer cells differ from normal cells and lead to more effective personalized cancer therapies in the future.”

Methionine is one of nine amino acids (AAs)—these are the building blocks that our bodies use to make proteins—that are known as “essential.” The human body lacks the machinery to make methionine from scratch, so we can only acquire this amino acid from our diets. Poultry and legumes are examples of foods that are rich in methionine...

 

[Daniel E.]

https://www.sciencedirect.com/science/article/pii/S2213231721000884

May 2021

Methionine restriction (MR) extends lifespan and delays the onset of aging-associated pathologies. However, the effect of MR on age-related cognitive decline remains unclear. Here, we find that a 3-month MR ameliorates working memory, short-term memory, and spatial memory in 15-month-old and 18-month-old mice by preserving synaptic ultrastructure, increasing mitochondrial biogenesis, and reducing the brain MDA level in aged mice hippocampi....

It may be concluded that MR attenuates the cognitive decline caused by aging. The nutritional response signal, FGF21, is required for MR-mediated protection of neurological function and upregulation of hippocampal mitochondrial biogenesis. These results suggest that dietary restriction or specific essential amino acid restriction may be designed as nutritional interventions to prevent age-related cognitive disorders.

 

[Daniel E.]

Stage IV Pancreatic Cancer Patient Treated With FOLFIRINOX Combined With Oral Methioninase: A Highly-Rare Case With Long-term Stable Disease

Background: Pancreatic cancer is one of the most recalcitrant cancers, and more effective therapy is needed. Pre-clinical studies have shown that patient-derived orthotopic xenograft (PDOX) mouse models of pancreatic cancer are effectively treated with oral recombinant methioninase (o-rMETase)...

ar.iiarjournals.org

Background: Pancreatic cancer is one of the most recalcitrant cancers, and more effective therapy is needed. Pre-clinical studies have shown that patient-derived orthotopic xenograft (PDOX) mouse models of pancreatic cancer are effectively treated with oral recombinant methioninase (o-rMETase).

Case Report: A 62-year-old woman diagnosed with stage IV pancreatic cancer was treated with the combination of 5-fluorouracil/leucovorin, irinotecan, and oxaliplatinum (FOLFIRINOX) every two weeks and o-rMETase twice a day as a supplement. The patient was also on a low-methionine diet. Disease progression was monitored by CA19-9 and computed tomography. The patient initially responded to FOLFIRINOX, shown by a great reduction in CA19-9 levels, with tumor shrinkage shown by computed tomography. The patient began taking o-rMETase and went on a low-methionine diet one year after diagnosis which she has maintained without side effects for 7 months. The patient’s CA19-9 level and tumor size remain stable 19 months after diagnosis. The patient is alive and has maintained a high performance status. Historical data show that less than 5% of stage IV pancreatic-cancer patients on FOLFIRINOX have stable disease 1.5 years after diagnosis.

Conclusion: The combination of o-rMETase and FOLFIRINOX may be synergistic in stage IV pancreatic cancer.

 

[Daniel E.]

Molecular mechanisms of dietary restriction promoting health and longevity - Nature Reviews Molecular Cell Biology

Dietary restriction in rodents and non-human primates affects key nutrient-sensing signalling pathways to increase healthspan and lifespan. This Review discusses these geroprotective mechanisms and recent insights suggesting that dietary restriction results in similar molecular and metabolic...

www.nature.com

Restriction of methionine​

It has been proposed that a selective reduction of specific, essential amino acids might be sufficient to extend healthspan and lifespan independently of total protein and calorie intake. Methionine, threonine, tryptophan and branched-chain amino acids (BCAAs) have all been identified as potential candidates.

In 1993, Orentreich and colleagues observed that lifelong ~80% methionine restriction resulted in a 30% increase in lifespan in male rats198; these findings were subsequently confirmed in mice199. As illustrated in Supplementary information 4, methionine reduction has strong beneficial effects on the metabolic health of rodents, and reduced consumption of methionine potentially contributes to the health of humans consuming vegan diets. Methionine plays a unique role in translation, as methionine is specified by the AUG start codon and is thus required for translation initiation of most proteins. Methionine restriction thus has a dramatic effect on protein translation, strongly downregulating protein synthesis200. In addition to these effects, which may be beneficial for healthy ageing, methionine also has important and unique metabolic roles and effects that have been implicated in the benefits of methionine restriction.

Many of the metabolic adaptations to methionine reduction have been attributed to the actions of the hormone FGF21, the levels of which are upregulated by methionine restriction or depletion in both young and aged mice201,202,203. As with protein restriction, a reduced dietary intake of methionine increases energy expenditure by promoting a FGF21-dependent browning of white adipose tissue204. ‘Browning’ refers to a phenotypic switch where white adipose tissue becomes enriched in mitochondria and upregulates expression of uncoupling protein 1 (UCP1). This promotes thermogenesis and energy expenditure, resulting in reduced adiposity. This effect is independent of GCN2, and is induced by the activation of the eIF2α kinase PERK205 as a consequence of methionine restriction-induced oxidative stress resulting from depletion of glutathione. Dietary supplementation with cysteine blocks the effect of methionine restriction on FGF21 levels, adiposity and energy expenditure205,206.

Alterations in dietary methionine levels strikingly and rapidly lead to changes in the levels of its metabolites — the universal methyl donor S-adenosylmethionine (SAM) and cysteine, a key precursor of antioxidant glutathione and the gaseous messenger hydrogen sulfide (H2S)207. SAM is crucial for histone and DNA methylation, and methionine restriction causes substantial reductions of SAM levels and alterations to both DNA and histone methylation208,209,210. Changes in the levels of metabolites such as SAM and S-adenosylhomocysteine are thought to drive the protection against hepatic DNA hypomethylation with age in adult mice208, and might account for the stronger effects on metabolic health seen with methionine restriction rather than leucine restriction on hepatic lipogenic gene expression and circulating FGF21 (ref.211). H2S, a powerful vasodilator, is endogenously produced via the trans-sulfuration pathway, and may help protect from multiple age-related diseases207,212. Production of H2S is required for DR to extend C. elegans lifespan213. Finally, methionine restriction activates AMPK in mice214, which is required for the lifespan extension induced by increased synthesis of SAM in yeast215.

SAM levels are also sensed by mTORC1 via SAMTOR, and a reduction in SAM levels leads to decreased mTORC1 signalling216. However, even complete methionine depletion does not significantly alter hepatic mTORC1 activity, and mice lacking liver Tsc1, which have constitutively active hepatic mTORC1, respond normally to a methionine-deprived diet203. Thus, at least in the liver, reduced mTORC1 signalling does not mediate many of the metabolic effects of methionine restriction. Further research will be required to fully define the molecular mechanisms underlying the geroprotective effects of methionine restriction.

 

[Daniel E.]

Methionine​

Martin Kohlmeier, in Nutrient Metabolism, 2003

The Met-content of proteins varies considerably depending on the food source. Foods with a particularly high percentage include eggs (31 mg/g protein), cod (30 mg/g), and chicken (28 mg/g). Intermediate content is in beef (26 mg/g), pork (26 mg/g), milk (25 mg/g), and rice (24 mg/g). Grains and other plant-derived protein sources tend to contain a lower percentage. Examples are corn (21 mg/g), wheat and oats (18 mg/g), rye and beans (15 mg/g), and cauliflower (14 mg/g). Cooking foods at high temperatures (browning) can decrease Met bioavailability due to oxidation (Dworschak, 1980).

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ClinicalTrials.gov

clinicaltrials.gov

Rice, Wheat, Chickpeas and Lentils as a food source contain low amounts of the essential amino acid methionine (Chickpeas and Lentils) and lysine (Rice and Wheat) which makes its protein incomplete.

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https://www.texaschildrens.org/sites/default/files/uploads/Cystinuria_handout.pdf


Amounts listed above are estimates of methionine content. Unless otherwise stated, foods are listed in standardized portion sizes: ½ cup serving or medium size whole fruit or vegetable,1 oz nuts, 2 Tbsp peanut butter, 2 oz meat, ½ cup beans. (SOURCE: USDA Nutrient Database Release 28)

 

[Daniel E.]

Of course, with beef and other animal products, one can use half (or less) of the regular amount and substitute with something else like beans, lentils, peas, mushrooms, etc.

Regarding peas, they are low in methionine (and cysteine) compared to rice:

Rice protein - Wikipedia

en.wikipedia.org

Rice protein is commonly mixed with pea protein powder. Rice protein is high in the sulfur-containing amino acids, cysteine and methionine, but low in lysine. Pea protein, on the other hand, is low in cysteine and methionine but high in lysine.

 

[Daniel E.]

Methionine- Restricted Diet… Who needs it? - Brenda Davis RD

Methionine is an essential amino acid — one of the building blocks of protein that cannot be produced by the human body so must come from our food. It is one of two sulfur-containing amino acids (the other is cysteine). Methionine is an intermediary in the synthesis of cysteine, carnitine...

www.brendadavisrd.com

Vegetables	Weight	Measure	Methionine (mg)
Asparagus, cooked	180 g	1 cup	50
Green beans, cooked	125 g	1 cup	29
Yellow beans, cooked	135 g	1 cup	24
Beets, cooked, sliced	170 g	1 cup	32
Broccoli rab, raw, chopped	40 g	1 cup	19
Broccoli, raw, chopped	91 g	1 cup	35
Burdock root, raw	118 g	1 cup	11
Cabbage, chinese, cooked, shredded	179 g	1 cup	15
Cabbage, cooked	150 g	1 cup	9
Carrots, raw, chopped	128 g	1 cup	26
Cauliflower, raw, chopped	107 g	1 cup	21
Celery, raw, chopped	101 g	1 cup	5
Chard, swiss, raw	36 g	1 cup	7
Chard, swiss, cooked	175 g	1 cup	35
Collards, raw	36 g	1 cup	12
Collards, cooked	170 g	1 cup	68
Cucumber, raw	104 g	1 cup	6
Eggplant, cooked	99 g	1 cup	9
Endive, raw	50 g	1 cup	8
Kale, raw, chopped	67 g	1 cup	18
Kale, cooked	130 g	1 cup	23
Kohlrabi, raw	135 g	1 cup	18
Leeks, cooked	124 g	1 leek	12
Lettuce, raw, shredded	36-47 g	1 cup	6-7
Mountain yam, cooked	145 g	1 cup	33
Mushrooms, cooked	156 g	1 cup	34
Mustard greens, cooked	150 g	1 cup	32
Okra, cooked	160 g	1 cup	32
Onions, cooked	210 g	1 cup	23
Parsley, fresh, chopped	60 g	1 cup	25
Pepper, sweet, raw, chopped	149 g	1 cup	9
Pumpkin, cooked, mashed	245 g	1 cup	20
Radicchio, raw	40 g	1 cup	3
Radishes, raw	116 g	1 cup	12
Seaweed, laver, raw	26 g	10 sheets	38
Spinach, raw	30 g	1 cup	16
Squash, summer, cooked	180 g	1 cup	23
Squash, winter, cooked	205 g	1 cup	23
Taro, cooked, sliced	132 g	1 cup	9
Tomatoes, fresh	149 g	1 cup	9
Tomato sauce	245 g	1 cup	17
Turnip greens, cooked	144 g	1 cup	37
Turnips, cooked, cubes	156 g	1 cup	14
Watercress, raw	34 g	1 cup	7
Yam, cooked	136 g	1 cup	27
Yardlong bean, cooked	104 g	1 cup	37
Zucchini, raw, chopped	124 g	1 cup	22
Brussels sprouts, cooked	155 g	1 cup	54
Hearts of palm, canned	146 g	1 cup	61
Potatoes, white + skin	148 g	1 med	56
Spinach, cooked	180 g	1 cup	99
Sweet potato, cooked	200 g	1 cup	74
Corn, sweet, cooked	165	1 cup	112
Peas, cooked	160 g	1 cup	130
Peas, raw	145 g	1 cup	119
Fruits
Apples, raw, sliced	125 g	1 cup	1
Apricots, dried	65 g	0.5 cup	10
Apricots, raw	155 g	1 cup	9
Bananas, raw, mashed	225 g	1 cup	18
Blueberries, raw	148 g	1 cup	18
Cherimoya, raw	160 g	1 cup	34
Cranberries, raw, chopped	110 g	1 cup	3
Dates	147 g	1 cup	32
Figs, raw	64 g	1 large (2.5″)	4
Gogi berries, dried	28 g	5 Tbsp	24
Grapefruit sections	230 g	1 cup	12-18
Grapes, fresh	92 g	1 cup	19
Guava, fresh	165 g	1 cup	26
Kiwi, raw, sliced	180 g	1 cup	43
Limes, raw	67 g	1 fruit	1
Mango, raw	165 g	1 cup	13
Melon, cantaloupe, raw	177 g	1 cup	21
Melon, honeydew, raw	170 g	1 cup	8
Nectarines, raw, sliced	143 g	1 cup	8
Olives, ripe, jumbo	15 g	1	2
Orange, raw, sections	180 g	1 cup	36
Papaya, raw	145 g	1 cup	3
Peach, raw	154 g	1 cup	15
Pear, Asian, raw	122 g	1 fruit	7
Pear, raw, slices	140 g	1 cup	3
Persimmons, raw	25 g	1 fruit	2
Pineapple, raw, chunks	165 g	1 cup	20
Plantains, raw, sliced	148 g	1 cup	25
Plums, raw, sliced	165 g	1 cup	13
Plums, dried	174 g	1 cup	28
Raisins, seedless	165 g	1 cup	35
Strawberries, raw	152 g	1 cup	3
Tangerines, raw, sections	195 g	1 cup	4
Watermelon, raw, balls	154 g	1 cup	9
Avocado, raw, cubes	150 g	1 cup	57
Figs, dried	149 g	1 cup	51
Jackfruit, raw	165 g	1 cup	56
Legumes
Black-eyed peas, cooked	165 g	1 cup	74
Hummus, homemade	60 g	1/4 cup	48
Miso	17 g	1 Tbsp	22
Okara	122 g	1 cup	50
Soy sauce (tamari)	18 g	1 Tbsp	30
Soy sauce (wheat and soy shoyu, low Na)	14 g	1 Tbsp	13
Soy milk, fortified	243 g	1 cup	39
Fava beans, cooked	170 g	1 cup	105
Lentils, sprouted, raw	77 g	1 cup	81
Lima beans, cooked	170 g	1 cup	116
Pigeon peas, red gram	168 g	1 cup	128
Soybeans, sprouted, cooked	94 g	1 cup	84
Tofu, soft	120 g	2.5 x 2.75 x 1″	101
Tofu, regular (medium firm)	124 g	0.5 cup	134
Tofu, firm (with calcium sulfate and nigari)	126 g	0.5 cup	139
Veggie sausages	50 g	2 links	126
Adzuki beans, cooked	230 g	1 cup	182
Chickpeas, cooked	164 g	1 cup	190
Cowpeas, cooked	171 g	1 cup	188
Kidney beans, cooked	177	1 cup	200
Lentils, cooked	198	1 cup	152
Lupins, cooked	166 g	1 cup	183
Mung beans, cooked	202 g	1 cup	170
Refried beans, canned reduced sodium	238 g	1 cup	155
Split peas, cooked	196 g	1 cup	167
Black turtle beans, cooked	185 g	1 cup	228
Black beans, cooked	172 g	1 cup	229
Cranberry beans, cooked	177 g	1 cup	248
Edamame, cooked	155 g	1 cup	215
Great Northern beans, cooked	177 g	1 cup	221
Navy beans, cooked	182 g	1 cup	201
Pink beans, cooked	169 g	1 cup	230
Small white beans, cooked	179 g	1 cup	242
Veggie burgers or soyburgers	70 g	1 patty	204
Tempeh	166 g	1 cup	290
Tofu, firm (prepared with calcium sulfate)	126 g	0.5 cup	266
White beans, cooked	179 g	1 cup	261
Soybeans, mature, cooked	172 g		385
Soy nuts, dry roasted	93 g	1 cup	497
Grains
Hominy, yellow	160 g	1 cup	50
Tapioca, uncooked	38 g	0.25 cup	1
Noodles, japanese, soba, cooked	114 g	1 cup	82
Barley. cooked	157	1 cup	68
Buckwheat groats, cooked	168 g	1 cup	74
Cornmeal	39 g	0.25 cup	64
Pasta, wheat, cooked	124 g	1 cup	79
Pasta, gluten-free, cooked, corn and quinoa	166 g	1 cup	98
Pasta, gluten-free, cooked, corn	140 g	1 cup	77
Sorghum grain, uncooked	48 g	0.25 cup	81
Triticale, uncooked	48 g	0.25 cup	98
Rice, white, long grain	158 g	1 cup	100
Amaranth, uncooked	48 g	0.25 cup	109
Millet, cooked	174 g	1 cup	122
Oats, uncooked	39 g	0.25 cup	122
Oat bran, cooked	219 g	1 cup	109
Pasta, gluten-free, cooked, brown rice	169 g	1 cup	134
Pasta, gluten-free, cooked, corn and rice	141 g	1 cup	102
Rice, brown, long grain	202 g	1 cup	117
Spelt, uncooked	44 g	0.25 cup	112
Wheat bran	58 g	1 cup	136
Wheat, hard, uncooked	48 g	0.25 cup	111
Wheat, sprouted	108 g	1 cup	125
Quinoa, cooked	185 g	1 cup	178
Kamut, cooked	172 g	1 cup	167
Wild rice, cooked	164 g	1 cup	195
Teff, uncooked	48 g	0.25 cup	207
Teff, cooked	252 g	1 cup	315
Nuts
Acorns, dried	28.35 g	1 ounce	39
Almonds	28.35 g	1 ounce	44
Almond butter	16 g	1 Tbsp	20
Cashew butter	16 g	1 Tbsp	50
Chestnuts, dried, European	28.35 g	1 ounce	33
Coconut, fresh, shredded	80 g	1 cup	50
Coconut, dried, shredded	28.35 g	1 ounce	37
Coconut water	240 g	1 cup	31
Macadamia nuts	28.35 g	1 ounce	7
Coconut milk, canned	240 g	1 cup	86
Hazelnuts	28.35 g	1 ounce	63
Pecans	28.35	1 ounce	54
Pine nuts	28.35 g	1 ounce	59
Peanuts, dry roasted	28.35 g	1 ounce	82
Walnuts, English	28.35 g	1 ounce	67
Cashews	28.35 g	1 ounce	103
Pistachio nuts	28.35 g	1 ounce	102
Brazil nuts	28.35 g	1 ounce	319
Seeds
Tahini (sesame seed butter), raw	15 g	1 Tbsp	88
Flaxseeds	28.35	1 ounce	105
Sunflower seeds	28.35 g	1 ounce	119
Chia seeds	28.35 g	1 ounce	167
Pumpkin seeds	28.35 g	1 ounce	171
Sesame seeds	28.35 g	1 ounce	159
Hempseeds (about 3 Tbsp)	28.35 g	1 ounce	264
Animal products
Eggs	33 g	1 large	132
Cheese, brie	28.35	1 ounce	168
Cheese, gouda	28.35	1 ounce	204
Milk, 1%	245 g	1 cup	215
Milk, 3.25%	244 g	1 cup	203
Yogurt, low fat, fruit	170	6 ounces	219
Cheese, parmesan, hard	28.35	1 ounce	272
Yogurt, plain, skim milk	170	6 ounces	287
Beef, lean, cooked	85 g	3 ounces	648
Chicken breast, cooked	85 g	3 ounces	675
Crab, cooked	134 g	1 leg	730
Fish, cod	85 g	3 ounces	448
Fish, salmon	85 g	3 ounces	640
Fish, tuna, canned	85 g	3 ounces	733
Ham, cooked	85 g	3 ounces	435
Lobster, cooked	145 g	1 cup	689
Pork, cooked	85 g	3 ounces	609
Shrimp, cooked	85 g	3 ounces	565
Turkey, roasted	85 g	3 ounces	670

NOTES:

1. These figures in this table were sourced from the USDA National Nutrient Database for Standard Reference Release 28. http://ndb.nal.usda.gov/ndb/nutrients/index

1. The chart is set up using food groups (e.g. vegetables, fruits, legumes, etc.). Within each group, you will notice a variety of colors which represent different categories of methionine concentration (see key that precedes the chart). Within each color category, foods appear in alphabetical orde

 

[Daniel E.]

Our laboratory has developed a methioninase that can be administered orally as a supplement and has resulted in anecdotal positive results in patients with advanced cancer, including hormone-independent prostate cancer, and other recalcitrant cancers. The question is whether methionine restriction through a low-methionine diet, or even greater methionine restriction with methioninase in combination with a low-methionine diet, is ready for prime time in the clinic, especially in combination with other synergistic therapy. The question will hopefully be answered in the near future, especially for advanced cancer patients who have failed all standard therapy.

I contacted AntiCancer.com for a price quote. For the indefinite future, the pricing is obviously for research institutions only. Basically, 100 days of methioninase supplementation for a human is $5,000 USD. This dosing is based on previous research, which uses 500 units a day. To buy even a small amount appropriate for a single mouse would be $200 for a 10-day supply (1,000 units total for 100 units each day).

Related book for researchers: Methionine Dependence of Cancer and Aging | SpringerLink

A relatively free alternative to methioninase is glycine:

https://faseb.onlinelibrary.wiley.com/doi/abs/10.1096/fasebj.25.1_supplement.528.2

Amino acids in the regulation of aging and aging-related diseases

Amino acids are the building blocks of protein, but also play important cellular signaling roles. The mechanisms through which altered levels of many …

www.sciencedirect.com

And:

Health Benefits of the Mediterranean Diet: Metabolic and Molecular Mechanisms

Consuming a Mediterranean diet rich in minimally processed plant foods has been associated with a reduced risk of developing multiple chronic diseases and increased life expectancy. Data from several randomized clinic trials have demonstrated a beneficial ...

www.ncbi.nlm.nih.gov

Dietary methionine intake is on average 40% lower in the traditional Mediterranean diet.

 

[Daniel E.]

Fitness and Exercise | Penn State Extension

Looking for information on weight management through exercise and fitness? Expand your knowledge with our Extension Educators’ tips on active living.

extension.psu.edu

The three most common plant protein sources are soy, brown rice, and pea protein. Unlike whey and casein, plant based protein sources do not contain all of the essential amino acids that the body needs. However, this type of supplement would be a good option for consumers who are vegan or those with a lactose intolerance or allergy.

 

[Daniel E.]

Methionine restriction improves renal insulin signalling in aged kidneys - ScienceDirect

Our results indicate that dietary MR may offer therapeutic potential in ameliorating the renal functional decline related to ageing and other disorders associated with metabolic dysfunction by enhancing renal insulin sensitivity and renoprotective gene expression.

 

[Daniel E.]

How diet affects tumors

MIT researchers analyzed ketogenic and calorically restricted diets in mice, revealing how those diets affect cancer cells and offering an explanation for why restricting calories may slow tumor growth.

news.mit.edu

Although this study showed that calorie restriction has beneficial effects in mice, the researchers say they do not recommend that cancer patients follow a calorie-restricted diet, which is difficult to maintain and can have harmful side effects. However, they believe that cancer cells’ dependence on the availability of unsaturated fatty acids could be exploited to develop drugs that might help slow tumor growth.

One possible therapeutic strategy could be inhibition of the SCD enzyme, which would cut off tumor cells’ ability to produce unsaturated fatty acids.

Mice fed a lipogenic methionine-choline-deficient diet develop hypermetabolism coincident with hepatic suppression of SCD-1 - PubMed

Lipogenic diets that are completely devoid of methionine and choline (MCD) induce hepatic steatosis. MCD feeding also provokes systemic weight loss, for unclear reasons. In this study, we found that MCD feeding causes profound hepatic suppression of the gene encoding stearoyl-coenzyme A...

pubmed.ncbi.nlm.nih.gov

Mice fed a lipogenic methionine-choline-deficient diet develop hypermetabolism coincident with hepatic suppression of SCD-1.

Stearoyl-CoA 9-desaturase - Wikipedia

en.wikipedia.org

Elevated expression levels of SCD1 is found to be correlated with obesity [20] and tumor malignancy.[21] It is believed that tumor cells obtain most part of their requirement for fatty acids by de novo synthesis. This phenomenon depends on increased expression of fatty acid biosynthetic enzymes that produce required fatty acids in large quantities.[22]

Mice that were fed a high-carbohydrate diet had an induced expression of the liver SCD-1 gene and other lipogenic genes through an insulin-mediated SREBP-1c-dependent mechanism. Activation of SREBP-1c results in upregulated synthesis of MUFAs and liver triglycerides. SCD-1 knockout mice did not increase de novo lipogenesis but created an abundance of cholesterol esters.[23]

 

[Daniel E.]

Lecturer: Michael Lustgarten, PhD | Jean Mayer USDA Human Nutrition Research Center on Aging

Papers referenced in the video:

Life-Span Extension in Mice by Preweaning Food Restriction and by Methionine Restriction in Middle Age

Low methionine ingestion by rats extends life span

Fasting glucose level and all-cause or cause-specific mortality in Korean adults: a nationwide cohort study https://pubmed.ncbi.nlm.nih.gov/32623...

Total plasma homocysteine and cardiovascular risk profile. The Hordaland Homocysteine Study https://pubmed.ncbi.nlm.nih.gov/7474221/

Predicting Age by Mining Electronic Medical Records with Deep Learning Characterizes Differences between Chronological and Physiological Age https://www.ncbi.nlm.nih.gov/pmc/arti...

Association between low-density lipoprotein cholesterol and cardiovascular mortality in statin non-users: a prospective cohort study in 14.9 million Korean adults https://pubmed.ncbi.nlm.nih.gov/35218...

Blood counts in adult and elderly individuals: defining the norms over eight decades of life https://pubmed.ncbi.nlm.nih.gov/32030...

 

[Daniel E.]

Salmon protein as overrated:

No effect of salmon fish protein on 2-h glucose in adults with increased risk of type 2 diabetes: a randomised controlled trial | British Journal of Nutrition | Cambridge Core

No effect of salmon fish protein on 2-h glucose in adults with increased risk of type 2 diabetes: a randomised controlled trial - Volume 126 Issue 9

www.cambridge.org

We found no significant effect of salmon fish protein supplementation on our primary outcome or other markers related to glucose tolerance, serum lipids, weight or blood pressure compared with placebo. The present study does not support the hypothesis that daily intake of a salmon fish protein supplement for 8 weeks improves glucose tolerance in persons with increased risk of T2DM [type 2 diabetes mellitus].

 

[Daniel E.]

METHIONINE: Overview, Uses, Side Effects, Precautions, Interactions, Dosing and Reviews

Learn more about METHIONINE uses, effectiveness, possible side effects, interactions, dosage, user ratings and products that contain METHIONINE.

www.webmd.com

Methionine is an amino acid. Amino acids are the building blocks that our bodies use to make proteins. Methionine is found in meat, fish, and dairy products. It plays an important role in the many functions within the body.

Too much methionine can cause brain damage and death. Methionine can increase blood levels of homocysteine, a chemical that may cause heart disease. Methionine might also promote the growth of some tumors.

 

[Daniel E.]

Learning How to Starve a Tumor

By studying cancer growth in mice eating different diets, scientists are learning what makes tumors thrive—and what might weaken them and slow their growth.

www.webmd.com

The healthy tissues of the body still need these nutrients, one reason patients with cancer shouldn’t change their diets without clinical guidance. But the findings hint that using diet or drugs to restrict intake of some lipids or their use cells could be a path to starving a tumor without starving the person.

 

[Daniel E.]

You Can’t ‘Starve’ Cancer, but You Might Help Treat It With Food

There is no single “cancer diet.”

www.theatlantic.com

...The closest thing to a methionine-restricted diet is, in practice, a vegan diet. This would seem to be at odds with the cancer-fighting effects reported by Mukherjee and colleagues involving a “ketogenic” diet. But contrary to the dietary wars that plague the pages of popular media, Mukherjee was supportive of Locasale’s investigation. “More evidence about the fascinating connection between diet and cancer,” he tweeted of the Duke study. “It’s not ‘starving’ the cancer, but rather finding precise vulnerabilities that make metabolic therapies feasible.”

And so now I have begun referring to food as metabolic therapy.

Because cancer is a term that encapsulates many different diseases—with different changes in different metabolic pathways in different cells in different parts of the body—no single metabolic therapy is right for every person. What makes one cancer grow more slowly could conceivably hasten another. Just as avoiding excessive sugar is crucial for people with diabetes, lest they lose their vision and feet, sugar can save the life of a person with critical hypoglycemia.

In 2017, I reported on a provocative study of vitamin B12 supplements, which can prevent anemia in people who don’t get enough through food. In excessive amounts, though, using these supplements was associated with higher rates of lung cancer. Again, this seemed to be by way of a metabolic pathway that fuels the tumor cells.

Nutrients or vitamins are not simply good or bad, cancer-causing or cancer-fighting. If a book or blog recommends a single “cancer diet”—or even a supplement that promises to fight cancer—beware. It could end up making things worse. Especially if there is a person on the cover in a white coat with arms folded, and with teeth that look like they have never been used.

For now, unless an oncologist has advised a specific diet tailored to your specific tumor, the most common recommendation is to eat a generally healthy diet. None of this challenges the principle that staying well nourished is part of a healthy approach to any disease; and there is no evidence that overall starvation is good or even safe. But focusing on specific patterns of eating will likely be part of many cancer-treatment guidelines in coming years.

Food is medicine—or metabolic therapy. And no metabolic therapy is good or bad for everyone in every condition.

 

[Daniel E.]

Cancer research: New advances and innovations

For the second part of our 'what's exciting the experts' series, we contacted cancer researchers and asked what cancer research they find most fascinating.

www.medicalnewstoday.com

​

Use for an antidepressant?​

“Our study from late 2020 has shown that the antidepressant sertraline helps to inhibit the growth of cancer cells in mice,” Prof. Kim De Keersmaecker from KU LEUVEN in Belgium told MNT.

“Other studies had already indicated that the commonly used antidepressant has anticancer activity, but there was no explanation for the cause of this. We’ve been able to demonstrate that sertraline inhibits the production of serine and glycine, causing decreased growth of cancer cells.”

Cancer cells and healthy cells are often reliant on the amino acids serine and glycine, which they extract from their environment. However, certain cancer cells produce serine and glycine within the cell. They can become “addicted” to this production.

This internal production of serine and glycine requires certain enzymes, and these enzymes have become targets for cancer researchers. Preventing them from functioning can “starve” the cancer cells.

Previous studies have identified inhibitors of serine/glycine synthesis enzymes, but none have reached the clinical trial stage. As the authors of a KU LEUVEN study note, because “sertraline is a clinically used drug that can safely be used in humans,” it might make a good candidate.

Prof. De Keersmaecker explained that “when used with other therapeutics, the drug strongly inhibited the growth of cancer cells in the mice.”

The authors of the study concluded: “Collectively, this work provides a novel and cost efficient treatment option for the rapidly growing list of serine/glycine synthesis-addicted cancers.”

 

[Daniel E.]

https://www.cancertherapyadvisor.com/home/decision-support-in-medicine/labmed/hypermethioninemia/

Elevations of methionine are very common in liver disease. Prematurity of the liver enzymes may cause a pattern of elevated methionine and tyrosine. Methionine and tyrosine are typically elevated in multiple forms of acquired and inherited liver disease.