5 replies to this topic

[recon]

I thought methionine deficient diets are supposed to correlate with greater health span. It’s supposed to be almost equivalent to CR.

However, a paper by Katsyuba 2007 cites another study and noted that “[m]ethionine-/choline-deficient (MCD) diet (Gariani et al, 2017) also leads to the concomitant appearance of liver fat accumulation and a drop in hepatic NAD+ levels.” [1]

So is restricting methionine even a good idea now that it is known that NAD+ levels are reduced by such a diet?


Reference:
[1]
Modulating NAD(+) metabolism, from bench to bedside.
Katsyuba E, et al. EMBO J. 2017 Sep 15;36(18):2670-2683. doi: 10.15252/embj.201797135. Epub 2017 Aug 7.
https://www.ncbi.nlm...ubmed/28784597/

Edited by recon, 11 November 2017 - 03:18 AM.

[tunt01]

I think it's because choline converts to betaine, which is involved in the BHMT pathway of remethylation conversion of homocysteine back to methionine, in one-carbon metabolism.  There are various papers discussing deficiencies in choline and how they cause NAFLD (Non-alcoholic fatty liver disease).

 

The issue with methionine is that it contains a sulfur group, which soaks up ROS at a faster rate than other amino acids that do not contain a sulfur group.  

 

 

 

Switching of methionine metabolism between the disposal (a) and conservation (b) modes is regulated by AdoMet. The thick arrows qualitatively depict increased metabolic flux. The dashed lines indicate activation (red ) and inhibition (blue) by AdoMet to control flux in response to low and high methionine supply. Abbreviations: AHC, AdoHcy hydrolase; GNMT, glycine N-methyltransferase; MAT-I/III, liver-specific methionine adenosyltransferase isoforms I and III; MT, methyltransferase. (Kabil 2014)    

 

I think the issue in low methionine diets is inappropriate recycling of AdoMet which often shows up as higher levels of homocysteine, such that choline becomes quite important.  The other issue with choline is that certain gut bacteria metabolize it to TMAO at different rates, and everyone seems to have a different choline requirement based on their own intestinal microbiome.  (Romano 2017)

 

 

Darryl or someone with more knowledge of one-carbon metabolism of choline can probably add greater depth to this issue.  Looking at this matter is on my long long to-do list.

 

 

Kabil O, Vitvitsky V, Banerjee R. Sulfur as a Signaling Nutrient Through Hydrogen Sulfide. Annual review of nutrition. 2014;34:171-205. doi:10.1146/annurev-nutr-071813-105654.

 

Romano, K., Martinez-del Campo, A., Kasahara, K., Chittim, C., Vivas, E., & Amador-Noguez, D. et al. (2017). Metabolic, Epigenetic, and Transgenerational Effects of Gut Bacterial Choline Consumption. Cell Host & Microbe, 22(3), 279-290.e7. doi:10.1016/j.chom.2017.07.021

 

 

 

Edited by prophets, 11 November 2017 - 01:53 PM.

[tunt01]

Also, what's kind of interesting about that passage of Katsyuba, et al is the first part that you left out:

 

Orotic acid administration (Fukuwatari et al, 2002) or feeding a methionine-/choline-deficient (MCD) diet (Gariani et al, 2017) also leads to the concomitant appearance of liver fat accumulation and a drop in hepatic NAD+ levels

 

 

This may speak to why some people have been concerned with orotic acid as being hepatocarcinogenic as seen in lithium orotate.  Maybe the amount in the supplements people are taking are absolutely tiny compared to the risk, similar to how cyanide is part of cyanocobalamin (B12) supplements.  IDK the numbers offhand.

 

This is a nice review paper from Auwerx lab on NAD+.  I might read it all.

Edited by prophets, 11 November 2017 - 02:01 PM.

[recon]

Also, what's kind of interesting about that passage of Katsyuba, et al is the first part that you left out:

Orotic acid administration (Fukuwatari et al, 2002) or feeding a methionine-/choline-deficient (MCD) diet (Gariani et al, 2017) also leads to the concomitant appearance of liver fat accumulation and a drop in hepatic NAD+ levels

This may speak to why some people have been concerned with orotic acid as being hepatocarcinogenic as seen in lithium orotate. Maybe the amount in the supplements people are taking are absolutely tiny compared to the risk, similar to how cyanide is part of cyanocobalamin (B12) supplements. IDK the numbers offhand.

This is a nice review paper from Auwerx lab on NAD+. I might read it all.

Thank you so much for the reply.
Occasionally I have questions like these and posted them to (notoriously) no reply.

So if I’m getting this correctly, a low methionine diet should be coupled with appropriate consumption of choline, but as of now, dosages for choline are still a bit unsubstantiated because of individualised conversion to TMAO?

And, yeah, I didn’t see the significance of the orotic acid part until you pointed it out. I’ve just gotten my lithium orotate. What a bummer.
I was initially just opting to change my L-Optizinc (zinc monomerhionine) to reduce dietary methionine but I’m unsure about that now.
But for sure, I’m going to have to find a replacement for my lithium orotate.

[LenaW]

Recon,

 

I use Lithium Aspartate.  

 

 

[tunt01]

Per Methionine/sulfur containing amino acids, see this other longecity thread, particularly the video covering this subject matter.