Could cutting this one nutrient make you live longer?

It was first reported in 1993 that rats subjected to a diet restricted in methionine (MR) enjoyed comparable life spans copared to rats that were on caloric restriction (CR).  In the first experiments, methionine was reduced to ⅕ its normal level in the diet, and growth of the rats was severely stunted.

What is methionine?

Proteins are the workhorse chemicals of the body, macromolecules consisting of folded chains of sometimes tens of thousands of amino acid molecules strung together.  There are 20 amino acids to choose from*, and the particular sequence of amino acids in the chain determines how the protein will fold up (“tertiary structure”), and thus what shape it will have, and thus how it will function in the body.

When we eat protein, it is “someone else’s” long chain protein molecules that we ingest.  The particular form that the protein takes was useful to the plant or animal that we’ve eaten, but not to us, so our digestion breaks down the protein into the component amino acids, and then rebuilds the protein chains we need from these “recycled” pieces.  Of the 20 amino acids, our bodies rely exclusively on the foods we eat to get 8 of them, the “eight essential amino acids” made famous by Frances Moore Lappé 40 years ago.  The other 12 we can manufacture for ourselves.

 Costs and Benefits

Various rodents fed on a low-methionine diet have been observed to live longer.  In some of these experiments, food intake was strictly controlled to assure that the MR animals and the controls received the same total calories. [ref]

 Oxidative damage from the mitochondria is a hallmark of aging, and this has been noted to decrease reliably with methionine restriction.  [href]  The authors of this article “conclude that methionine is the only dietary factor responsible for the decrease in mitochondrial ROS production and oxidative stress, and likely for part of the longevity extension effect, occurring in DR.” This may be an extreme, if tenable position.

Methionine restriction lowers cancer rates, and has been proposed as a cancer treatment, logically enough since it limits cell growth.

 

The Start Codon

Here’s a clue about why methionine is special.  The instructions for making proteins is coded into DNA, via the genetic code, which specifies words of 3 DNA letters, each corresponding to one of the 20 amino acids.  The genetic code also contains “punctuation”, instructions to start and stop.  The “start codon” is also the word for methionine.  Every chain of amino acids that the body constructs begins with methionine.

 No methionine – no protein synthesis.  A shortage of methionine means that the body is inhibited in making every kind of protein.  I remarked a few months back that more genes are expressed (more proteins synthesized) as the body grows older.  Perhaps methionine restriction is putting a brake on this production of extra proteins (that are not produced when we’re young).

 Paradoxes

SAMe is a supplement I take.  The “Me” in SAMe is for “methionine”, which is part of the chemical formula.  SAMe promotes methylation of DNA, which decreases gene expression, which (theoretically) extends life by a similar mechanism to methionine restriction.  Go figure. 

Methionine is a necessary ingredient for the body to synthesize glutathione, “the mother of all anti-oxidants“ and a longevity factor.  And yet, less methionine has been associated with more glutathione.

Toward a Practical Diet 

We can’t live entirely without methionine – the body would not be able to make any proteins at all.  Restricting methionine is likely to have impacts on growth, health, and wellbeing that are as yet unstudied in humans.  “rats fed a diet without methionine developed steatohepatitis (fatty liver), anemia and lost two thirds of their body weight over 5 weeks.”  (Wikipediia) In one experiment, ⅕ of the mice died, and the other ⅘ went on to live longer than control mice.

A separate issue is how to accomplish methionine restriction in practice.  Proteins that we eat consist of chains of amino acids with all 20 mixed in.  Even if you chew your food very carefully, it is not practical to just spit out the methionine and swallow the rest.  So methionine restriction in practice involves eating foods that are low in methionine.  Though all protein has methionine, some protein sources are much lower in methionine than others.  I compiled the following table from data available at USDA Nutirtion reference site.

Food (100g)

% Methionine

Calories

fat g

carb g

protein g

cal fr fat

cal fr carb

cal fr protein

Frozen Peas

0.47%

52

0.38

9.02

3.5

6.37%

67.93%

25.70%

Almonds 100g

0.86%

597

52.83

19.29

22.09

74.22%

12.18%

13.60%

Lentils

0.93%

116

0.38

20.13

9.02

2.84%

67.62%

29.54%

Mung Beans

1.05%

105

0.38

19.15

7.02

3.15%

71.35%

25.50%

Split peas

1.07%

118

0.39

21.1

8.34

2.88%

70.10%

27.02%

Peanuts 100g

1.22%

585

49.66

21.51

23.68

70.26%

15.06%

14.68%

Tofu 100g

1.32%

145

8.72

4.27

15.78

38.37%

31.21%

30.43%

Chick Peas 100g

1.36%

164

2.59

27.42

8.86

24.77%

38.09%

37.14%

Walnuts

1.50%

654

65.21

13.71

15.23

83.55%

7.90%

8.55%

Black beans

1.59%

130

0.35

24.35

8.18

2.35%

73.56%

24.09%

Cashews

1.60%

576

46.35

32.69

15.31

68.41%

21.69%

9.90%

Broccoli 100g

1.61%

35

0.41

3.88

2.38

16.25%

42.40%

41.34%

Wheat Gluten 100g

1.65%

370

1.85

13.79

75.16

2.70%

49.27%

48.04%

Boiled peas

1.91%

84

0.22

15.63

5.36

2.29%

73.22%

24.48%

Wheat Germ 100g

2.01%

382

10.7

49.6

29.1

23.39%

48.73%

27.88%

2% Milk 100g

2.39%

50

1.97

4.68

3.3

40.21%

30.27%

29.52%

Roast Beef

2.68%

163

4.1

0

29.59

24.02%

0.00%

75.98%

Chicken

2.72%

300

20.97

0

25.95

64.84%

0.00%

35.16%

Eggs

2.95%

142

9.9

0.76

12.53

62.93%

2.17%

34.90%

Salmon 100g

3.07%

182

8.13

0

25.44

26.47%

37.23%

36.30%

Tuna

3.07%

139

1.22

0

29.97

8.50%

0.00%

91.50%

Sardines 100g

3.07%

208

11.45

0

24.62

34.38%

33.23%

32.39%

Egg white 100g

3.39%

52

0.17

0.73

10.9

3.22%

6.22%

90.56%

Brazil nuts

6.50%

656

66.43

12.27

14.32

84.93%

7.05%

8.02%

You can see that all animal sources (including milk and especially eggs) are high in methionine.  So an MR diet is a vegan diet, not just any vegan diet, but a subset of vegan protein sources.  There appear to be no general rules.  For example, almonds are a good source of low-methionine protein, but Brazil nuts are terrible.  Lentils are first-rate, soy beans not so good, and wheat germ is poison.

A long shot idea

Glycine is the simplest of the 20 amino acids.  (It is literally just an amine group linked to an acid group, NH2CH2COOH.)   It was reported at an experimental biology conference two years ago that increasing glycine has similar effects to decreasing methionine in the diet, showing life extension and some of the same metabolic benefits in rats.  To my knowledge, this has not yet been written up in a peer-reviewed journal.  I’ve written to the author, and will add a comment below this post if I hear anything.

_______
*not to be confused with the nucleic acids that make up DNA.  There are only 4 of those.

This article originally appeared here: http://joshmitteldorf.scienceblog.com/2013/05/13/could-cutting-this-one-nutrient-make-you-live-longer/

 

1 Response

  1. May 13, 2013

    […] Peter It was first reported in 1993 that rats subjected to a diet restricted in methionine (MR) enjoyed […]

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