D-Arginine and D-ornithine metabolism in CFS/IBS

The data from 14 people to date reporting in the microbiome metabolism explorer has a high percentage with a very low metabolism for D-Arginine and D-ornithine (10/14). There are a few others that are high (4/10). None normal. This variation is expected because everyone’s shift is different.

At face value,  this means that both arginine and ornithine that is taken into the body is not effectively processed and suggest high levels of both would be in the body OR low levels of chemicals they produce.

Diagram from Arginine Metabolism: Boundaries of Our Knowledge [2007]

m_1602sfig1

This agrees with other findings:

Arginine

  • “These results indicated that L-Arg induces iNOS and generates NO, which inhibits EBV reactivation in EBV-positive cells.” [2002]
    • With a low metabolism, the amounts of  inducible nitric oxide synthase (iNOS) and nitric oxide (NO) produce would drop considerably and EBV would become re-activated! The mechanism of inactivation of  EBV cells is lost.  You are EBV positive/reactivated? this is likely the why!
    • Also it explains low iNOS and NO reported from studies.
      • Decreased nitric oxide-mediated natural killer cell activation in chronic fatigue syndrome [1998] “These results demonstrate that the L-Arg-induced activation of NK activity is mediated by NO and that a possible dysfunction exists in the NO-mediated NK cell activation in CFS patients.”
      • “There were significant and positive intercorrelations between COX-2, iNOS and NFkappabeta and between COX-2 and iNOS, on the one hand, and the severity of illness, on the other. The production of COX-2 and iNOS by PBMCs was significantly related to aches and pain, muscular tension, fatigue, concentration difficulties, failing memory, sadness and a subjective experience of infection. ” [2007] – lower iNOS => more severe.

Ornithine

Again, the products produce from this amino acid will be greatly reduced.

  • “From these findings, we speculated that L-ornithine may play a role in the relieve of stress and improve sleep and fatigue symptoms in humans. Through a randomised, double-blind, placebo-controlled clinical study, we asked if L-ornithine could be beneficial to stress and sleep in healthy workers…. L-ornithine supplementation has the potential to relieve stress and improve sleep quality related to fatigue, both objectively and subjectively.” [2014]
  • l-Ornithine affects peripheral clock gene expression in mice. [2016] “. l-Ornithine also increased plasma levels of insulin, glucose and glucagon-like peptide-1 alongside mPer2 expression, suggesting that it exerts its effects probably via insulin secretion. Collectively, these findings demonstrate that l-ornithine affects peripheral clock gene expression and may expand the possibilities of L-ornithine as a health food.”

Leaky Gut

“Arginine and ornithine are precursors of nitric oxide and polyamines, respectively. These metabolites intimately participate in permeability and adaptive responses of the gut. The liver possesses high arginase activity as an intrinsic part of urea synthesis and would consume most of the portal supply of dietary arginine. The gut reduces this possibility by converting dietary arginine to citrulline, which effectively bypass the liver and is resynthesized to arginine in the kidney. Dietary ornithine supplementation, in the form of ornithine alpha-ketoglutarate (OKG) can be considered as an arginine precursor. Several supplement studies have shown both amino acids to promote growth hormone and insulin secretion with anabolic effects in postoperative patients. Their intermediary metabolites (for example, glutamine, proline) may also be of benefit in trauma metabolism. Specific effects of either amino acid on the gut are poorly reported.” [1994]

Bottom Line

Remember that this estimation of D-Arginine and D-ornithine metabolism is based off your gut bacteria nothing else is known about you, no blood sample etc.

  • We see that this explains EBV reactivation
  • “aches and pain, muscular tension, fatigue, concentration difficulties, failing memory, sadness and a subjective experience of infection.” for low arginine
  • ” to relieve stress and improve sleep quality related to fatigue” and likely sleep reversal and insomina — for low ornithine

With time, I hope to have this pattern confirmed from the uBiome and symptoms shared on our analysis site.

I was unable to identify from scanning the literature, the bacteria that are important for this metabolism (hopefully a reader will find such!).

If your metabolism function is estimated to be low, then supplementation with both Ornithine and arginine seems to be suggested. With arginine, convention wisdom is that lysine should be taken with it.

There is no clear study dealing with low metabolism. Ornithine occurs is very low amounts in food and thus with a reduce metabolism, taking more may produce more end products.

If you have herpes, care need to be taken:

“In the studies conducted, arginine deficiency suppressed herpes simplex virus replication in tissue culture. Lysine, an analog of arginine, as an antimetabolite, antagonized the viral growth-promoting action of arginine. The in vitro data may be the basis for the observation that patients prone to herpetic lesions and other related viral infections, particularly during periods of stress, should abstain from arginine excess and may also require supplemental lysine in their diet.” [1981]

In this case zinc supplements with Glutamine may be an alternative approach.

In the case of arginine, we read of additional side-effects from too much. From livestrong.com

Digestive Problems

L-arginine can increase levels of stomach acid, particularly gastrine. Too much gastrine can result in stomach pain and nausea. You may also experience bloating, cramps and diarrhea.

Allergic Reactions

Some people experience anaphylaxis, or an allergic reaction, to L-arginine. The severity of anaphylaxis increases with dosage. Symptoms include itches and skin rashes, swollen eyes, and in the worst cases, shortness of breath. People with asthma may be especially prone to this.

Blood Pressure

Because of L-arginine’s properties as a vasodilator, low blood pressure can be a side effect of supplementation. If you experience low blood pressure, you may notice dizziness, fainting or blurred vision. Contact your doctor immediately if you experience these or other associated symptoms.”

This is an education post to facilitate discussing this approach with your medical professionals. It is not medical advice for the treatment of any medical condition. Always consult with your medical professional before doing any  changes of diet, supplements or activity. Some items cites may interfere with prescription medicines.

 

 

We need more data…

But a symptom of hair loss has some strong trends (3/3) had
* Low Amino acid metabolism: D-Arginine and D-ornithine metabolism .233
* Low Bacterial Abilities: Bacterial chemotaxis .658
* Low Bacterial Abilities: Bacterial motility proteins .658
* Low Bacterial Abilities: Flagellar assembly .575
* Low Secondary metabolite degradation: Dioxin degradation .74
* Low Secondary metabolite degradation: Xylene degradation . 825

See http://microbiomeprescription.com/Metabolite/Explorer?filter=,116

Data Downloads are now available

All of the user entered data is available for citizen scientists (as well as some AI scientists and statisticians with significant others having CFS). This was a promise that I made in collecting the data — make the data freely available without any human identifying information.

Data is now available formatted for intake to R or other statistical software at:

https://citizenscience.microbiomeprescription.com/

As is seen below, this data has been available for 5+ years and the volume of data has growth much

Downloads

Bottom Line

The data is there for any professional or amateur research to use. The greatest value comes when people provide their symptoms and copies the function/metabolites numbers into this shared repository.

CFS/FM/IBS Metabolism deep dives — Fundamentals

On the ubiome function/metabolism report there are several different terms being used which I wish to try to give definition/explanation for the brain-fogged. See this post on how you can contribute to this data

The most important and common are the three shown below.

Metabolism

This means the conversion of a named item into different parts and the parts being reassemble back to the named item.  This of oxygen and carbon dioxide: plants converts carbon dioxide to oxygen, humans convert oxygen to carbon dioxide.

  • If the value is 0.8 – 1.2 , you are naturally producing a normal flow of this item
  • If the value is below 0.8. the flow is reduced. Some if the different parts may be too high or too low (think of baking a cake — too much flour and not enough eggs — if one is out  of step then things are not right).
  • If the value is over 1.2, you may have greater than normal flow. Some if the different parts may be too high or too low (think of baking a cake — too much flour and not enough eggs — if one is out  of step then things are not right).

Needless to say — this gets complex because we are not told the details.

More literature:

Degradation

AKA biodegradation. This means the ability to breakdown specific items into component parts. We can think of this as the ability to clear items from your body.

Low values suggests excessive accumulation. High values may result in being short of this item because it is aggressively removed.

More literature

Biosynthesis

This means that the named item is being produced from the various bacteria from simple chemicals you have.

  • If the value is 0.8 – 1.2 , you are naturally producing a normal amount of this item
  • If the value is below 0.8. supplementation (if available) would be suggested
  • If the value is over 1.2, you may be over-producing this items and may wish to:
    • Eliminate it from supplements or foods rich in it
    • Reduce the bacteria that is producing it (if known)
    • Encourage consumers.

Both High and Low would be expected to cause symptoms.

More literature:

Deep Dives in Metabolism

The following will be the target of subsequent posts (which will be linked to as they are written)

Amino acid metabolism

  1. AverageAlanine, aspartate and glutamate metabolism
  2. Arginine and proline metabolism
  3. beta-Alanine metabolism
  4. Cyanoamino acid metabolism
  5. Cysteine and methionine metabolism
  6. D-Alanine metabolism
  7. D-Arginine and D-ornithine metabolism
    1. Low
    2. Take Ornithine, Arginine (with Lysine), Zinc, glutamine
  8. D-Glutamine and D-glutamate metabolism
  9. Glutathione metabolism
  10. Glycine, serine and threonine metabolism
  11. Histidine metabolism
  12. Lysine biosynthesis
  13. Lysine degradation
  14. Phenylalanine metabolism
  15. Phenylalanine, tyrosine and tryptophan biosynthesis
  16. Phosphonate and phosphinate metabolism
  17. Selenocompound metabolism
  18. Taurine and hypotaurine metabolism
  19. Tryptophan metabolism
  20. Tyrosine metabolism
  21. Valine, leucine and isoleucine biosynthesis
  22. Valine, leucine and isoleucine degradation

Bacterial Abilities

  1. AverageBacterial chemotaxis
  2. Bacterial motility proteins
  3. Bacterial secretion system
  4. beta-Lactam resistance
  5. Cell division
  6. Cell motility and secretion
  7. Flagellar assembly
  8. Lysosome
  9. Phagosome
  10. Sporulation

Carbohydrate metabolism

  1. AverageAmino sugar and nucleotide sugar metabolism
  2. Ascorbate and aldarate metabolism
  3. Butanoate metabolism
  4. C5-Branched dibasic acid metabolism
  5. Citrate cycle (TCA cycle)
  6. Fructose and mannose metabolism
  7. Galactose metabolism
  8. Glycolysis / Gluconeogenesis
  9. Glyoxylate and dicarboxylate metabolism
  10. Inositol phosphate metabolism
  11. Pentose and glucuronate interconversions
  12. Pentose phosphate pathway
  13. Propanoate metabolism
  14. Pyruvate metabolism
  15. Starch and sucrose metabolism

Lipid metabolism

  1. Averagealpha-Linolenic acid metabolism
  2. Arachidonic acid metabolism
  3. Biosynthesis of unsaturated fatty acids
  4. Ether lipid metabolism
  5. Fatty acid biosynthesis
  6. Glycerolipid metabolism
  7. Glycerophospholipid metabolism
  8. Linoleic acid metabolism
  9. Sphingolipid metabolism
  10. Steroid biosynthesis
  11. Steroid hormone biosynthesis
  12. Synthesis and degradation of ketone bodies

Secondary metabolite biosynthesis

  1. Average Betalain biosynthesis
  2. Butirosin and neomycin biosynthesis
  3. Caffeine metabolism
  4. Flavone and flavonol biosynthesis
  5. Flavonoid biosynthesis
  6. Indole alkaloid biosynthesis
  7. Isoquinoline alkaloid biosynthesis
  8. Novobiocin biosynthesis
  9. Penicillin and cephalosporin biosynthesis
  10. Phenylpropanoid biosynthesis
  11. Stilbenoid, diarylheptanoid and gingerol biosynthesis 
    1. HIGH
    2. Take Ginger, Turmeric, Resveratrol, Almonds
  12. Streptomycin biosynthesis
  13. Tropane, piperidine and pyridine alkaloid biosynthesis

Secondary metabolite degradation

  1. AverageAminobenzoate degradation
  2. Atrazine degradation
  3. Benzoate degradation
  4. Bisphenol degradation
  5. Caprolactam degradation
  6. Chloroalkane and chloroalkene degradation
  7. Chlorocyclohexane and chlorobenzene degradation
  8. Dioxin degradation
    1. LOW and deteriorate over time.
    2. Take Activated Charcoal, Resveratrol
  9. Drug metabolism – cytochrome P450
  10. Drug metabolism – other enzymes
  11. Ethylbenzene degradation
  12. Fluorobenzoate degradation
  13. Metabolism of xenobiotics by cytochrome P450
  14. Naphthalene degradation
  15. Nitrotoluene degradation
  16. Polycyclic aromatic hydrocarbon degradation
  17. Styrene degradation
  18. Toluene degradation
  19. Xylene degradation

Vitamin metabolism

  1. AverageBiotin metabolism
  2. Folate biosynthesis
  3. Lipoic acid metabolism
  4. Nicotinate and nicotinamide metabolism
  5. One carbon pool by folate
  6. Pantothenate and CoA biosynthesis
  7. Porphyrin and chlorophyll metabolism
  8. Retinol metabolism
  9. Riboflavin metabolism
  10. Thiamine metabolism
  11. Ubiquinone and other terpenoid-quinone biosynthesis
  12. Vitamin B6 metabolism

 

Five people have added their…

Five people have added their metabolite profile from uBiome to their data.
http://microbiomeprescription.com/Metabolite/explorer

One item sticks out greatly — very low D-Arginine and D-ornithine metabolism for all five.
If you happen to have any readings on treating D-Arginine and D-ornithine metabolism , please forward to me.
My initial take is that means that D-arginine and D-ornithine does not get processed much resulting in a build up. This suggests a low arginine and low ornithine diet could be considered.
“Some of the best choices are soybeans, pumpkin seeds, sesame seeds, peanuts and walnuts. You’ll also get it from sweet green peppers and the seaweed spirulina. Grains such as quinoa, oats and wheat germ deliver arginine, as do a variety of ready-to-eat cereals made from oats, rice and wheat.” https://www.livestrong.com/article/275892-foods-high-in-l-arginine/

I need to do more digging, but hope some of you have already done it and are willing to share!