Eating less helps you live longer, but eating less is hard.  One line of experiment suggests that eating less of just one protein component, methionine, is sufficient to extend life span, perhaps as effectively as though less calories were being consumed.  It’s an intriguing idea, though the research is fraught with contradictions, and to separate methionine from other protein components is not easy or cheap.

It was first reported in 1993 that rats subjected to a diet restricted in methionine (MR) enjoyed comparable life spans 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 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.

Methionine is one of these eight essential amino acids, and one of just two that include the element sulfur.

 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.  [ref]  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 CR.”  In other words, the only reason that caloric restriction extends life span is that the body gets less methionine in the process. This may be an extreme, if tenable position.  I don’t believe that an experiment has yet been done in which rodents are fed a diet that is both high in methionine and low in calories.

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, and that contribute to aging.

 

 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 where methionine was severely restricted but not eliminated entirely, 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, you can’t just spit out the methionine and swallow the other 19.  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 refrence 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.

The table also makes clear that even a strict vegan diet (free of Brazil nuts) would only reduce methionine intake by about 1/2.  Extrapolating from the rodent experiments, we may need to reduce by ~ 3/4 before crossing a threshold where benefits kick in.

(Note incidentally that CR is not like this.  There is no threshold for caloric restriction.  Eating less increases life span quite smoothly.  You get a little benefit from eating a little less, and a lot of benefit from eating a lot less.)

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.

 

Bottom line

The number of experiments that have been done with methionine restriction is tiny compared to caloric restriction.  There is no data at all, that I am aware of, for humans on a methionine-restricted diet.  It’s an intriguing idea, and I’m guessing that more study of methionine restriction will yield interesting insights into aging.  I don’t think we know enough  yet to consider adopting MR as an aid to long-term health, especially since severe restriction is likely to have side-effects, and mild restriction is is likely to be ineffective. 

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