Proline Inhibits Mitochondria

[xploit316]

@Wishful Have you experimented with Lamb or Mutton to see if you get similar benefits to eating Beef? Carnitine, iron, B12 higher in grass fed red meat helping with balancing/metabolizing proline?

 

[Wishful]

Have you experimented with Lamb or Mutton to see if you get similar benefits to eating Beef?

I was planning to try that next trip into town. I only go to town every 3 weeks or so, so experimentation is slow. It's not the carnitine or B12 content, since I tried those in supplement form, and it didn't help.

I could try snaring a snowshoe hare, since they're eating lots of grass and clover,


... but they're so cute!

 

[Wishful]

Have you experimented with Lamb or Mutton

Lamb does seem as effective as beef at countering the proline sensitivity. One lamb chop a day was enough to allow me to eat wheat and dairy without triggering extra symptoms. It also increased my time between waking during the night the same as beef.

I'm doubtful that the steaks I bought 'price reduced' at Walmart are premium grass-fed beef. It's more likely something to do with ruminant digestion.

 

[Wishful]

I may have stumbled upon the active component in beef: conjugated linoleic acids (CLAs). They're much more abundant in ruminant meats (fats) and dairy products than in other meats. They fit the profile of what I was looking for, and they certainly do have biological effects. I'll have to do more experimenting to verify that CLAs are responsible.

Sadly, beef doesn't seem as effective at blocking proline as the first few times, but it's still working somewhat.

 

[Wishful]

The last beef (fairly lean) didn't seem to have enough of the CLAs to counteract its proline content, so it just made me feel groggier. I tried some more lamb, and it seemed to counteract its proline, but not more than that.

I noticed my bottle of Evening Primrose Oil today. At one time, EPO seemed to help me sleep longer. I checked the label, and it has cis-linoleic acid. That's a bit different from conjugated linoleic acid, but maybe it was similar enough to partially block the proline.

 

[halcyon]

I assume that my present sensitivity to proline is unusual, so I don't think that ME is proline sensitivity. However, this link between proline and ME/PEM symptoms might be worth investigating further, so I'm posting this to see if it triggers some ideas in other people, or makes some researcher evaluate test results from a new perspective.

I would argue that the link may have more to do with proline's ability to agonize NMDA receptors. One of my top suspects for (some) post exertional symptoms in ME is quinolinic acid, another (potent) NMDA agonist.

 

[CSMLSM]

Cornstarch pancakes for two meals, for calories without problematic nutrients. Afternoon meal might be quinoa with onions and carrots. Some potato, rice or wheat (limited) snacks, plus milk in coffee or hot chocolate. Yes, very boring, and I wonder if it will drive me insane at some point, and I'll go chase down a bunny and eat it.

For protein, I'll have to figure out something for long-term, but I'm still in a 'seeing what happens' phase, and I'm not expecting any signs of protein deficiency any time soon. My legs feel a bit wobbly since the diet chance, so I think I'm missing something that I need, so it's more experimentation for me.



I think I may have had a slight sensitivity to it for a year or more before that, but I'm not certain. I had been wondering whether meat was worsening my symptoms, but I didn't do a definite controlled experiment. My reaction to protein during and after the 'viral infection (if that's what it was)' was dramatically more severe.

My frequent wakings started up several years ago, so if that was due to proline sensitivity, I've had part of the problem for a long time.

Firstly I have not read the whole thread and I apologise for that.

I would like to say that you are sensitive to an amino acid not protein.

Protein is built from amino acids. So you are sensitive to a building block of protein.

Amino acids are what you need in yor diet not protein. Protein is merely broken down into its constituent building blocks (amino acids) in the stomach by Gastric acid. You do not absorb protein from your diet, you absorb amino acids through your Gastric Mucosa.

Both animal and plant proteins are made up of about 20 common amino acids. The proportion of these amino acids varies as a characteristic of a given protein, but all food proteins—with the exception of gelatin—contain some of each. Amino nitrogen accounts for approximately 16% of the weight of proteins. Amino acids are required for the synthesis of body protein and other important nitrogen-containing compounds, such as creatine, peptide hormones, and some neurotransmitters. Although allowances are expressed as protein, a the biological requirement is for amino acids.

Proteins and other nitrogenous compounds are being degraded and resynthesized continuously. Several times more protein is turned over daily within the body than is ordinarily consumed, indicating that reutilization of amino acids is a major feature of the economy of protein metabolism. This process of recapture is not completely efficient, and some amino acids are lost by oxidative catabolism. Metabolic products of amino acids (urea, creatinine, uric acid, and other nitrogenous products) are excreted in the urine; nitrogen is also lost in feces, sweat, and other body secretions and in sloughed skin, hair, and nails. A continuous supply of dietary amino acids is required to replace these losses, even after growth has ceased.

Amino acids consumed in excess of the amounts needed for the synthesis of nitrogenous tissue constituents are not stored but are degraded; the nitrogen is excreted as urea, and the keto acids left after removal of the amino groups are either utilized directly as sources of energy or are converted to carbohydrate or fat.

You said you had caught a virus and this issue started following. The virus you caught likely caused extra immune dysfuction on top of your ME/CFS immune dysfunction. This immune dysfunction has been demonstrated to cause autoreactivity in people. This can cause your immune system to make problematic antibodies against your own building blocks. You maybe experiencing Autoimmunity to the Proline.
This can happen when taking high dose b12. People can actually become autoimmune to a vital vitamin for survial.

Here is something I wrote for someone else-

The underlying immune dysfunction leads to an activated adaptive immune response that itself is dysfunctional in nature.

Adaptive immunity is responsible for you developing memory of some infections and creates antibodies in response to this.

So this dysfunctional activated immune state leads to antibodies being dysfunctionally produced in response to you.

Plenty of you to react to and make antibodies based on you.

So to sum it up ME/CFS is not caused by autoimmunity it causes it, as a byproduct to the underlying issue- immune dysfunction caused by an underlying EBV infection or similar type of virus using similar mechanisms as EBV to persist in latency (stay infected past initial infection).

EBV is thought to be and I think also, to be the underlying driving force causing ME/CFS and even similar type viruses (there are many).
The virus preceding your symptoms may well have tipped the balance and lead to an antibody being produced against proline as it floats freely in the space where your immune cells also reside and exist.

I hope this helps. If you would like to know more you can checkout-
Members Only - Amazing resource (video) on Caryophyllene the science and potential! | Phoenix Rising ME/CFS Forums

You will find some videos about ME/CFS and also an option you may want to consider trying in this thread.

Hope you have a nice day

Daniel

 

[Wishful]

I would like to say that you are sensitive to an amino acid not protein.

Yes, that's why I specified proline. It took quite a bit of experimentation to identify which amino acid was responsible.

I noticed that I was no longer as sensitive to chicken, so I gave bacon another try. So far, it hasn't caused me any problems, so maybe my sensitivity to proline has diminished. I've also been feeling more energetic, doing a couple of hours of snow shovelling or tree limbing without problems (other than normal fatigue). I hope it keeps up.

 

[Wishful]

The virus preceding your symptoms may well have tipped the balance and lead to an antibody being produced against proline as it floats freely in the space where your immune cells also reside and exist.

I've thought about it, but I think it's more likely that the virus persisted after the main symptoms passed. Maybe it needed proline to produce one of its proteins that in turn worsened my symptoms.

Can antibodies react to individual amino acids? I couldn't find any reference to that.

 

[CSMLSM]

I've thought about it, but I think it's more likely that the virus persisted after the main symptoms passed. Maybe it needed proline to produce one of its proteins that in turn worsened my symptoms.

Can antibodies react to individual amino acids? I couldn't find any reference to that.

Antibodies can react to anything in theory. They simply need to bind to and prevent the action of what they bind to from happening (so cannot bind itself). They simply need to be the right shape. Molecular mechanics knowledge is what you need.

When I have finished trying to put 20 years research experience on here (currently held as a concept in my mind and not on paper) I should be able to point you to a resource that will help you visualise what I am talking about.
I am trying to basically put a training course together. No small task but what else am I suppose to do. I am struggling it seems to get anyone to believe in what I am saying much. I know what I say sounds too good to be true. I can assure you it is not too good to be true.

And yes the Proline could be being used as a substrate for another biological process you are correct this maybe happening.

Have a pleasant day

Daniel

 

[Shanti1]

Can antibodies react to individual amino acids? I couldn't find any reference to that.

I have never seen it documented. The variable portion on an antibody makes up about 110-130 amino acids and is designed as a lock-and-key with an antigen. I think a single amino acid would be too small and non-specific. Amino acids are free-floating in the blood, so if it occurred, I think it would have been reported.

Your thought on how you are metabolizing proline (or not metabolizing it, as the case may be) also seems probable. There certainly are lots of protein metabolism SNPs documented. It seems that a SNP in one of the proline enzymes could lead to symptoms. I think @halcyon 's NDMA observation is an interesting one and could work in tandem with proline metabolism issue.

Functional genomics and SNP analysis of human genes encoding proline metabolic enzymes

Abnormalities in proline metabolism are relevant in several diseases: six known monogenic inborn errors involving metabolism and/or transport of proline and its immediate metabolites have been described. In addition, impaired proline metabolism has been implicated as a susceptibility factor for schizophrenia, a complex neuropsychiatric disorder with a frequency of ~1% around the world.

I didn't read through the paper above to see if they named the 6 monogenetic disorders, but they typically run in families. You have been researching this a while, so have probably already come across this.

 

[CSMLSM]

I have never seen it documented. The variable portion on an antibody makes up about 110-130 amino acids and is designed as a lock-and-key with an antigen. I think a single amino acid would be too small and non-specific. Amino acids are free-floating in the blood, so if it occurred, I think it would have been reported.

Your thought on how you are metabolizing proline (or not metabolizing it, as the case may be) also seems probable. There certainly are lots of protein metabolism SNPs documented. It seems that a SNP in one of the proline enzymes could lead to symptoms. I think @halcyon 's NDMA observation is an interesting one and could work in tandem with proline metabolism issue.

Functional genomics and SNP analysis of human genes encoding proline metabolic enzymes


I didn't read through the paper above to see if they named the 6 monogenetic disorders, but they typically run in families. You have been researching this a while, so have probably already come across this.

Reading papers is one thing actually being able to comprehend the contents CONTEXT is vital you might like my new series I have just started called- Learn about series
I hope you like it

 

[Wishful]

I'm wondering whether my proline sensitivity following what I believe was a viral infection was actually some form of long-covid. I've felt much worse for the last year, but now quite abruptly I feel back to where I was before this occurred.

I did start being more active several weeks ago, but I'm not sure whether being more active helped, or whether I was more active because something else made the problem fade. I suppose it could be both.

I'm really quite delighted to finally get over whatever it was.

 

[SlamDancin]

@Wishful thats great news! I’m also having a resurgence but it’s been close to ten years since I’ve felt this well

 

[Shanti1]

@Wishful you may have seen this already, but it caught my eye a couple of weeks ago and I thought of your proline connection.

Mayneris-Perxachs J,et-al. Microbiota alterations in proline metabolism impact depression. Cell Metab. 2022 May 3;34(5):681-701. PMID: 35508109.
https://www.cell.com/cell-metabolism/pdfExtended/S1550-4131(22)00128-0

In brief:
Mayneris-Perxachs et al. apply a multiomics approach to study the microbiotagut-brain axis in depression and demonstrate that microbiome-dependent elevations in plasma proline are significantly associated with depression severity in humans. Proline supplementation exacerbated depression in mice, and knockdown of proline and GABA transporters or monoassociation with L. plantarum conferred protection against depression-like states in Drosophila.

Highlights

• High dietary and plasma proline significantly is associated with depression severity
• Circulating proline is dependent on microbiome composition and functionality
• With FMT, depression phenocopies to mice and increases a proline transporter gene
• Slc6a20 knockdown and L. plantarum supplementation protect flies from depression

 

[xploit316]

@Wishful Did anything else apart from CLA's help you counter the proline or is it under control now?

 

[Wishful]

Did anything else apart from CLA's help you counter the proline or is it under control now?

Nothing else made a difference. The sensitivity seems to be gone, for whatever reason, except that my double-vision still correlates with proline intake.