Limiting threonine and tryptophan

[corybroo]

MedicalXpress  https://medicalxpress.com/news/2020-06-essential-components-dietary-restriction-revealed.html has an article Essential components of dietary restriction revealed.

The researchers found "that by reducing the amount of two amino acids—threonine and tryptophan—in young healthy mice, they were able to burn more calories than they consumed, without calorie reduction, keeping them lean and healthy and without the side-effect of lower muscle mass. A low-threonine diet even protected mice that were morbidly obese and prone to developing type 2 diabetes."

The do caution  "While a moderate reduction in dietary protein and therefore essential amino acids can enhance vitality, diets devoid of this component can make people sick very quickly and are not recommended."

[Saul]

17 minutes ago, corybroo said:

The researchers found "that by reducing the amount of two amino acids—threonine and tryptophan—in young healthy mice, they were able to burn more calories than they consumed, without calorie reduction, keeping them lean and healthy and without the side-effect of lower muscle mass. A low-threonine diet even protected mice that were morbidly obese and prone to developing type 2 diabetes."

Interesting.  I wonder what they're healthspan and lifespan will be.  Studies have been done with animals given reduced methionine diets with positive results.

  --  Saul

Edited June 10, 2020 by Saul

[Ron Put]

Below is a study about methionine availability from chickpeas and rice.  It's likely that bioavailability of threonine and tryptophan from plant sources such as pulses is similarly less efficient because of the higher fiber content and other factors.

Bioavailable Methionine Assessed Using the Indicator Amino Acid Oxidation Method Is Greater When Cooked Chickpeas and Steamed Rice Are Combined in Healthy Young Men

The bioavailability of methionine from rice and from chickpeas was 100% and 63%, respectively. Complementation of cooked chickpeas with rice decreased the oxidation of l-[1-13C]phenylalanine by up to 14% (P < 0.05), suggesting an improved protein quality of the combined chickpeas plus rice protein.

[Saul]

For those of us interested in health and life extension, reduced methionine availability is a plus, rather than a minus.  So the study confrims:

(1) Don't eat rice (high calories; higher methionine content than desired in rice protein.  Same problem with all grains.)

(2) Eat your chickpeas and/or other legumes; they should be your primary source of protein -- rather than grain and/or animal protein.

  --  Saul

[Sibiriak]

Saul,  you quit eating your mega methionine  salmon every day?  Just curious...

[Saul]

Varies.  But I usually eat some salmon or other fish.

But no grains, eggs or dairy -- also rich sources of methionine.

  --  Saul

[Sibiriak]

Saul,  grains are NOT "rich" in methionine.  Their protein content is simply too low to begin with to provide high absolute amounts of methionine (and cysteine).

             100 grams of boiled brown rice provide a mere 58mg methionine  along with  31 mg of cysteine.  

             100 grams of raw salmon provide over TEN TIMES that amount,  a whopping - 626mg  methionine along with  219mg cysteine.

               (https://nutritiondata.self.com/)                                        

Eating salmon almost every day,  making fish your "main protein source",   will make a methionine/cysteine moderated diet more difficult to achieve .  On the other hand, if you eat a  primarily plant-based diet,  moderating overall protein,  your methionine/cysteine intake will be automatically reduced.

For a recent reviews of evidence for dietary sulfur amino acid restriction (SAAR) see:

Disease prevention and delayed aging by dietary sulfur amino acid restriction: translational implications  (2018)

The impact of dietary protein intake on longevity and metabolic health (2019)

The fact remains that most of that evidence  consists of  animal research bolstered with mechanistic speculation --   "current literature does not offer a complete understanding of the optimal SAA intake for end points such as longevity and chronic disease prevention in humans",  and there is  substantial "uncertainty whether the benefits of diets that restrict sulfur amino acids can be translated to humans."

Personally,  I don't eat rice,  but I do eat modest amounts of health-promoting buckwheat,  and occasionally oats or  rye,  and I pretty much follow Valter Longo's   protein restriction  recommendations. 

I also believe, following Levine, Longo et al,  that as one gets past around 65 yrs old one should consider  modestly increasing protein intake (including methionine/cysteine intake) to help prevent sarcopenia and frailty (depends a lot on the individual).

Edited June 21, 2020 by Sibiriak

[Sibiriak]

A key passage from the Threonine/Tryptophan restriction study:

 

Quote

[...]here we demonstrate that both Thr and Trp are equally limiting in the casein-based diet through empirical investigation, both by dietary AA restriction and by using a genetic model of AA-transport deficiency (Fig. 5). While this may seem contrary to those studies which have shown that restriction of certain EAA such as the branched chain AA (BCAA) or sulfur-containing AA (SCAA) are sufficient to mimic systemic metabolic response to DPD³⁷, this may be explained by titration thresholds dictated by ratios of dietary supply and somatic demand.

In particular, with regard to titration, basing the deprivation levels on the 5%E casein diet simply identifies those AA most limiting in this natural protein source, and that if we also restricted an AA to a theoretical level below which they would be limiting according to some somatic constraint²⁰, then this would likely trigger a similar response.

Indeed, even though Lys is an abundant AA in the milk protein casein, it is the most limiting EAA in protein derived from maize (i.e., zein)⁶¹, and the dietary supply of many EAAs are reduced in health-promoting vegan diets⁶². Nonetheless, it is known that certain EAA can be synthesised/spared by metabolism of precursors that can be mobilised within the body and/or supplied by diet⁵⁰.

In particular, systemic responses to restriction of the EAA Met can be alleviated by dietary Cys driven Met sparing^63,64,65. In addition, restriction of all three BCAA, but not leucine alone, recapitulates many of the features of total AA restriction²¹.

This metabolic compensation between BCAA is perhaps explained by that the metabolism of the three BCAA is linked by a single transaminase reaction⁶⁶, with rapid in vivo metabolism of BCAA, of which the liver is a major contributor⁶⁷, despite the absence of a BCAA transaminase in hepatocytes⁶⁶. Thus, we postulate that if one of the BCAA becomes limiting it can be spared by the other BCAAs, and their metabolism, within the tissue and between tissues.

In support of the concept of “metabolic sparing”, liver refurbishment of de novo biosynthesis of Thr abated the effects of dietary Thr restriction (Fig. 7). Thus we propose that it is the strictly metabolically EAA, namely Lys, Thr, and Trp, which have the potential to be most limiting in a particular diet.

Nonetheless, the differences in the sensitivity of AA restriction requires careful studies of nutritional EAA titration, especially as our studies were fully based on AA supply from a single nutritional source (i.e., the milk protein casein). This is a clear direction for future studies.

In addition, further studies are required to carefully dissect which EAA drive (mal)-adaptive processes during DPD, and in particular which do so under circumstances of altered somatic AA metabolism such as age-related disease, infection, or pregnancy.

Furthermore, as our studies were conducted in mice the relevance of our findings to human nutritional responses is vague without carefully controlled nutritional amino acid titration experiments using humans.

 

Edited June 21, 2020 by Sibiriak

[Saul]

Hi Sibiriac!

Of course my diet is plant based -- but it isn't vegan.  I eat a small amount of fish daily -- usually 3oz of raw salmon, or 2.5oz of hamachi (yellowtail).  Today may be an exception -- it's Father's Day in the US, and my wife and I will eat out in a restaurant.  I restrict protein -- biological age is not the same as chronological age.

The Finger Lakes region of NYS (which includes Rochester, NY) is in stage 3 of the reopening --  indoor restaurants are now open.

Happily, we have very little COV-19 infection.

  --  Saul

[Mike41]

16 hours ago, Sibiriak said:

 

I also believe, following Levine, Longo et al,  that as one gets past around 65 yrs old one should consider  modestly increasing protein intake (including methionine/cysteine intake) to help prevent sarcopenia and frailty (depends a lot on the individual

https://www.cambridge.org/core/journals/british-journal-of-nutrition/article/association-between-dietary-protein-intake-energy-intake-and-physical-frailty-results-from-the-rotterdam-study/EECE8004514CF09DC9DB3865B53CC0CD
 

yes indeed as you say depends a lot on the individual. My strategy is to get about 1 gm/ kg as some research suggests but focus on plant protein sources. Exercise, and proper nutrition Appear to be also very important.