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Author Topic: Amino acid testing and therapy  (Read 10278 times)

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alexk

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Amino acid testing and therapy
« on: March 28, 2010, 04:38:09 PM »

There's a lot of speculation about collagen and elastin on this forum, along with some theories that are difficult or impossible to prove (or disprove); for example, the theory that Peyronie's is an autoimmune disease. Amidst all this speculation, one fact is unassailable: if you don't have the necessary substrates and cofactors for making collagen and elastin, defective synthesis of connective tissue is inevitable.

I've noted before that the tunica albuginea, the affected structure in Peyronie's, is comprised primarily of collagen, with about 5% elastin (source: http://www.bumc.bu.edu/sexualmedicine/physicianinformation/male-genital-anatomy/). Collagen is synthesized from the amino acids lysine, proline, and glycine, in a reaction that is catalyzed by ascorbic acid (vitamin C). Elastin is synthesized from the amino acids glycine, valine, alanine, and proline, in a reaction that is catalyzed by lysine. Here's one study that found a "decreased percentage" of glycine and alanine in Peyronies Disease:
http://www.ncbi.nlm.nih.gov/pubmed/1606983

With this information in mind, has anyone on this forum ever had an amino acid profile? If there is a deficiency of any of the substrates for making collagen and elastin, due to genetic defects or dietary inadequacy, it would probably show up on the test. There are urine and plasma tests for amino acid levels, which can often be done together so that amino loss in the urine can be correlated with circulating levels of aminos in the blood.

For me, progress was extremely slow, even after a year of Pentox and vitamin E, until I started supplementing with lysine and vitamin C. I had an amino acid test done shortly thereafter, since the improvement was so profound. I was deficient in several of the amino acids mentioned above. I don't know if the reason was genetic or dietary, but amino acid therapy has been profoundly beneficial for me, to the point where Peyronies Disease is basically a footnote in my medical history. I would urge everyone on this forum to consider amino acid testing through a knowledgeable MD or a doctor of functional/integrative medicine (I've found the latter to be much more well-informed).

The importance of lysine in building collagen and elastin is one reason why I've questioned the use of L-arginine, since it competes with lysine for bodily uptake (meaning that more arginine equates to decreased availability of lysine). I took high doses of L-arginine (2-5g/day) for the greater part of a year. Although it definitely increased circulation, it didn't seem to affect the fibrosis at all, whereas lysine supplementation led to dramatic improvement within a week or two. I know that some doctors will suggest arginine for Peyronies Disease, but doctors are not infallible, and they prescribe all kinds of things that may or may not work. The MD who gave me a prescription for Pentox (Dr. Carson) said that he typically prescribes Pentox "with or without arginine," which would indicate that there's no strong evidence for the use of arginine.

The moral of the story is, "Don't guess; test." There are a lot of people on this forum spending money on supplements that showed results in medical studies, but may not make a difference to your particular physiology (or at worst, could be harmful). Amino acid tests typically check for 40+ amino acids, so you can get quite a bit of information for your money, instead of guessing what would work best for you based on generalized medical studies. Based on the results of those studies, you can take action. And if the amino tests show that you're fine, then you will know to look elsewhere for the cause of your symptoms.

If anyone has experience with this aspect of nutritional testing, I'd like to hear about it. I am definitely open to alternative theories about Peyronies Disease but they should be discussed on other threads. This is a thread about the role of amino acid testing and therapy for Peyronies Disease so please stay on topic.
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GS

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Re: Amino acid testing and therapy
« Reply #1 on: March 29, 2010, 01:41:39 PM »

Alexk,

So, are you saying that you feel like lysine is a better supplement than l-arginine?  And, are you also saying l-arginine might interfere with using lysine?

I am currently using l-arginine as a supplement, but not lysine; I'm wondering if I should reverse them and not take l-arginine?

GS
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alexk

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Re: Amino acid testing and therapy
« Reply #2 on: March 30, 2010, 02:29:56 PM »

So, are you saying that you feel like lysine is a better supplement than l-arginine?  And, are you also saying l-arginine might interfere with using lysine?

I don't think it's an issue of one being "better" than another, but I can say that arginine and lysine do compete with one another for uptake, and that supplementing with either one can reduce the availability of the other. In other words, if you take too much lysine you will be reducing your arginine level, which can have a negative effect on your circulation (in theory, and also in my personal experience). They key is to balance out your levels based on the right testing.

I am aware of the PAV cocktail. The P and V make sense to me, but not the A. The urologist that prescribed Pentox to me seemed to have a "take it or leave it" attitude regarding arginine. Most urologists don't know about this stuff anyway. They are not researchers and they don't get paid to be intellectually curious, they get paid to serve as dispensaries.

I took L-arginine for almost a year. It did seem to improve circulation, but did not have a noticeable effect on fibrosis. I started to develop cold extremities after exercising, which went away after I stopped taking arginine. I can't be sure of a true cause and effect but I have read that too much nitric oxide can actually diminish peripheral circulation and contribute to inflammation. It could vary with the individual. See research on Raynaud's syndrome or TMJ disorder for more info on the potential negatives of too much nitric oxide.

Again, let me stress that you should hesitate to take any individual amino acid unless you're deficient. You might just be wasting your money, because aminos are not necessarily stored in the body (it's complex) and you can only use so much of them at once. So you don't know what to take or how much of it to take unless you've had the right test. If the test shows that your aminos are fine, then that's good. You've ruled out another risk factor. In my case the amino deficiencies seemed to be a major issue, and addressing those deficiencies corrected a number of medical problems.
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alexk

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Re: Amino acid testing and therapy
« Reply #3 on: April 02, 2010, 11:31:42 AM »

OK, so nobody on the entire forum has done this kind of nutritional assessment? It seems like the most obvious place to start looking for issues with collagen integrity. If we could find a pattern in people's test results it could really change the way that Peyronies Disease is treated and understood.
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slowandsteady

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Re: Amino acid testing and therapy
« Reply #4 on: April 02, 2010, 12:38:14 PM »

I'd be interested in looking into it. I usually get my yearly testing done at LEF. They offer an "Amino Acid Profile Quantitative Blood Test" test for $103 for members (I get the membership just for the discount on the tests).

Thanks for bringing up these ideas, alexk.
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hornman

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Re: Amino acid testing and therapy
« Reply #5 on: April 02, 2010, 05:45:05 PM »

Alexk,

How much Lysine did you have to take to get your levels to the normal range.  I would think deficientcies would be rare since Amino Acids are plentyful in the foods we eat. Also could you give more details about your peyronies being history.  Are you completely cured now?

Hornman
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alexk

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Re: Amino acid testing and therapy
« Reply #6 on: April 02, 2010, 11:05:59 PM »

They offer an "Amino Acid Profile Quantitative Blood Test" test for $103 for members (I get the membership just for the discount on the tests).

That's a good price and it's a thorough test, which checks all the elastin/collagen-related aminos. Amino tests can be $300 or more if you're not getting them ordered by an MD. You can actually order these tests yourself through certain websites, but you won't have anyone to discuss the results with... although it might be self-explanatory, i.e. everything looks good except glycine, so take glycine. It might not be that simple though, because many of the aminos are connected... not always a simple issue of just making up for a deficiency. Probably best to get the test through a doctor who knows what they're looking at, and corroborate with your own research. But shop around for the right doctor, most MDs will just think you're being a hypochondriac.

How much Lysine did you have to take to get your levels to the normal range.  I would think deficientcies would be rare since Amino Acids are plentyful in the foods we eat.

I'm testing out a few other things before getting my aminos rechecked, but subjectively, I felt that 500mg-1g per day (divided doses) was the right amount for me. I will say that if you take too much lysine, you will negatively impact your circulation because of the competition between lysine and arginine. My hands and feet got cold if I took more than 1g/day. You could take it with arginine to counteract this, effectively raising both levels and keeping a balance, but if you actually had a shortage of lysine this wouldn't help as much. It's not just the lysine though, I was also deficient in other collagen and elastin-related aminos. No way for anyone to know their individual needs without testing.

You're right that amino acids are abundant in all foods but there are a lot of reasons for deficiencies. One is protein malabsorption, due to a high pH of the stomach acid or other GI issues. Another is dietary imbalance (junk food, sugars, etc). Stress and inflammation can lead to catabolism, which is a breakdown of existing tissue to generate amino acids for use as an energy source. This may be particularly true with some of the glucogenic aminos such as alanine. If you do some research you'll find that alanine is actually involved in prostate health as well and that people with conditions like BPH can be low in alanine.

There are also genetic variations in the way that people assimilate protein. There is a whole category of potentially fatal metabolic disorders that are due to failures in a single amino acid pathway. These disorders are often due to genetic mutations. It's to be expected that these types of mutations are prevalent in the normal population to a lesser degree. The essential amino acids come directly from the diet, but the non-essential aminos (like glycine, alanine, and proline) must be synthesized. I mention these three non-essential aminos because they are components of collagen and elastin. If there is a block in a synthesis pathway then you'll have a problem that can't be dealt with through diet alone.

The synthesis of non-essential aminos (transamination) also depends on vitamin cofactors like vitamin C and B6. The pathway can be working, but not as efficiently, due to shortages of these vitamins. History tells us about a whole group of serious, sometimes fatal diseases (pellagra, scurvy, beriberi, pernicious anemia, etc) that occurred due to a lack of a then-undiscovered vitamin. Deficiency of a single amino acid could cause similar problems. Maybe 50 years from now history will tell of a number of diseases that occur due to amino acid deficiencies.

Also could you give more details about your peyronies being history.  Are you completely cured now?

Hmm... subjectively, I'd say that if a urologist examined me now they'd have a pretty difficult time finding any trace of scar tissue. And when I first went to Dr. Carson he had no trouble giving me a Pentox prescription. Some of the worst spots are still palpable but they're improving every day and I'm confident that they will eventually disappear. Two years ago I was completely hopeless and in severe pain. I was repeatedly told that there was no cure. I'm glad I didn't listen to the so-called professionals. I'm not claiming that what worked for me will work for everyone but I do think this is a critical form of testing for people with Peyronies Disease.
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slowandsteady

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Re: Amino acid testing and therapy
« Reply #7 on: April 04, 2010, 02:28:29 PM »

Any thoughts on the amino acid l-proline? It and lysine are used in collagen synthesis, along with vitamin C.

Another reason that testing may pay off.

Further reading here:
Quote
Occasionally, however, the problem is not protein intake but the body’s inability to metabolize proline into the active form of hydroxyproline. Both acute and a chronic deficiency of vitamin C produce a significant increase in the proline to hydroxyproline ratio in urine,5 a sign that the conversion is not being made.5 Iron is another needed cofactor and vitamin C is well known to improve iron assimilation.8, 9, 10, 11
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alexk

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Re: Amino acid testing and therapy
« Reply #8 on: April 05, 2010, 10:49:17 PM »

You are right about proline. Glycine is part of collagen too. The issue is that lysine is essential (it has to be present adequately in the diet) while the other two are non-essential (they can be synthesized by the body). That's a simple description though because variations exist in each person's ability to convert each amino acid into others, and it also depends on the presence of certain cofactors and probably a thousand other things.

I did notice this in my amino results because I had a decent amount of proline, but very little hydroxyproline, and the ratio was in the lowest quintile (i.e. the lower 20% of people who had taken the test). I had only recently started taking vitamin C. I assumed that vitamin C would help with the proline hydroxylation, and took lysine directly to make up for any dietary deficiency.  But like you've said, the test is really critical to figure this out, otherwise it's all just speculation.

Speaking of speculation, here's another abstract I came across a while ago:
http://www.ncbi.nlm.nih.gov/pubmed/2753148

Synergistic enhancement of type I and III collagen production in cultured fibroblasts by transforming growth factor-beta and ascorbate

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Transforming growth factor-beta (TGF-beta) is a prototype of a family of polypeptides that regulates cellular growth and phenotypic differentiation. TGF-beta injection induces angiogenesis and fibrosis locally and stimulates the synthesis of extracellular matrix proteins, fibronectin, collagens, and proteoglycans in vitro in many cell types. Ascorbate is also known to induce collagen synthesis and to promote wound healing. We report that in cultured human skin fibroblasts, ascorbate and TGF-beta synergistically enhance the biosynthesis of type I and III collagens and their steady-state mRNAs. TGF-beta alone has no enhancing effect on type III collagen synthesis. The cooperation between ascorbate and TGF-beta may be of significance in wound healing and in disorders of fibrosis.

Here's another study I mentioned below, reposted for the excerpt that specifically mentions the different types of collagen, along with two amino acids:
http://www.ncbi.nlm.nih.gov/pubmed/1606983

Study of the changes in collagen of the tunica albuginea in venogenic impotence and Peyronie's disease

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We identified the collagen type and content of the tunica albuginea in Peyronie's disease and venogenic impotence compared with the tunica albuginea from the donor of the renal transplant and patients with penile injury. Type III collagen was detected obviously in Peyronie's plaque and was also present in venogenic impotence. It can be hardly found in normal controls. The ratios of type III to type I collagen were significantly higher in Peyronie's plaque while there was a moderate increase in venogenic impotence. The scarcity of type V collagen was noted in human tunica albuginea. The decreased percentage of glycine and alanine in Peyronie's disease and venogenic impotence implied the abnormal composition of collagen or presence of noncollagen protein. The results suggest the biochemical aberration of the tunica albuginea might interfere with the normal function of the penile drainage system.
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slowandsteady

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Re: Amino acid testing and therapy
« Reply #9 on: April 27, 2010, 12:38:45 PM »

I got my amino acid testing results back. The two aminos that were flagged for being outside the reference ranges were threonine (47.9 umol/L with the reference range being 76-261) and serine (57.1 umol/L with the reference range being 69-270).

My level of hydroxyproline was zero, but the reference range is 0-40. I mentioned hydroxyproline a few posts back. My proline level seems fine (hydroxyproline is synthesized from proline). Hydroxyproline requires vitamin C for conversion from proline. I took this test after a 13 hour fast, which might figure in.

Threonine is needed to make serine, so a low level of serine make sense given my low level of threonine. From this article:
Quote
Threonine is needed to create glycine and serine, two amino acids that are necessary for the production of collagen, elastin, and muscle tissue. Threonine helps keep connective tissues and muscles throughout the body strong and elastic, including the heart, where it is found in significant amounts. It also helps build strong bones and tooth enamel, and may speed wound healing or recovery from injury.

It is at least plausible that threonine deficiency could play a role in Peyronies Disease. Vegetarians are more likely to have it, but with my paleo-esque diet, I'm hardly a vegetarian. Perhaps a metabolism defect is involved.

s&s
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alexk

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Re: Amino acid testing and therapy
« Reply #10 on: June 15, 2010, 03:42:04 PM »

S&S, I rarely check the board so I didn't notice your results. Looks like you found a couple of anomalies that could be important. I'd be on the lookout for things that were also within the reference ranges, but moderately low (or high).

With amino testing, it's hard to say whether you're seeing typical body levels of AAs or if the test is more reflective of recent dietary intake. Since you were fasting when you took the test. From what I've been told, a blood test does the former, while a urine test does the latter. This would actually inform your test interpretation quite a bit because they're opposites in a way. What's in your blood is what you've got available for cell metabolism; what's in the urine is what you're losing. For example, some people have high levels of magnesium in their urine, which indicates that they're losing magnesium (i.e. from insulin issues), and not necessarily that they have too much of it in their diet... although if you do have too much magnesium in your diet, you will also lose it in the urine. So... two results, different interpretations.

FYI, my threonine level was fine (right around the 65th percentile, i.e. a little higher than the mean) and serine was borderline "too high" (around the 85th percentile). My nutritionist mentiond that the high serine would probably be related to high glycine intake (from magnesium glycinate). Since you mentioned taking glycine already, it seems weird that your serine level would be low (in either plasma or urine). Were you "fasting" from supplements too, or just food?

My hydroxyproline level was 5 umol/L, which was around the 15th percentile (meaning that 85% of the test population had a higher level of hydroxyproline than me). Like you, my proline level was also fine (around the 65th percentile). The ratio of hydroxyproline:proline was 0.026, which was around the 15th percentile again. That seemed problematic to me. You're right that Vitamin C (ascorbic acid) catalyzes the conversion from proline to hydroxyproline (as it does with lysine and hydroxylysine).

Anyway, it looks like you found something. I don't know what you do to treat a threonine deficiency or why you would have one, but it's telling that you had a deficiency of two amino acids that are involved in collagen synthesis. I maintain my prior statements that faulty collagen synthesis is to blame for Peyronies Disease. Even though we had different results, we still both had low levels of collagen-forming amino acids. It could be (as has been postulated before) that Peyronies Disease is a condition where varied causes lead to the same result. I think that's why it's really important for people to test for these things and come up with their own customized nutritional approach.
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goodluck

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Re: Amino acid testing and therapy
« Reply #11 on: July 24, 2011, 03:19:42 PM »

Interesting post and I think it behooves everyone to have this testing to see where they stand.  There is alot to be learned.

For what it is worth, Ryan Wellman's book on Peyronies suggest supplementing with Lysine 3g 2x a day and Proline 3g x2 a day.

My recent fasting urine organic acid test showed a number of low or low normal values.
Relevant to this topic are the following results:

Lysine was low 58 (144-634)

Threonine was low 100 (130-370)  (I mentioned this because another said theirs was low)

Proline was High at 5 (0)

Glycine was normal  1345  but in the lower quartile (730-4160)

Blood serum was taken at the same time after exercising for 15 minutes and yielded all normal excelpt B-Alanine.

B-Alanine high
Lysine was normal at 191  (116-296)
Glycine was normal at 356 (151-490)
Proline was normal at 208 (97-329)

I am not exactly sure how to interpret all of this. 
Apparently you are not suppose to have Proline in your urine. 
Not sure what it all suggests. 

Anyone have constructive comments?

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George999

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Re: Amino acid testing and therapy
« Reply #12 on: July 24, 2011, 06:07:03 PM »

Interesting conversation going on here.  I can only add that I have heard from multiple experts that older Americans in general simply do not get enough quality protein in their diet.  Most of them recommend significant supplementation with high quality whey protein, others with high quality soy protein.  Currently I am taking a good shot of premium whey protein made from grassfed sourced raw milk daily.  The focus on whey protein by these experts is due to their contention that whey protein is balanced, and contains numerous important co-factors that aid with assimilation.  - George
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goodluck

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Re: Amino acid testing and therapy
« Reply #13 on: July 25, 2011, 12:38:05 PM »

George,

I have read similar comments to yours.  I have been advised not to eat cow dairy per a food sensitivity testing.  I have started to take a goat protien powder made by Jarrow.  Too early to report anything.  I have read that goat dairy is easier on humans to digest.
I have also experimented with hemp protien powder.  I think you are right that it is not as balanced but it is an option for vegans. It has tons of fiber in it so you need to go easy on it at first and work up slowly.


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pless

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Re: Amino acid testing and therapy
« Reply #14 on: August 22, 2012, 07:29:49 PM »

"lysine supplementation led to dramatic improvement within a week or two".
alexk's post of March 28, 2010 was brilliantly fresh, and hopeful. Have there been any other reports of beating Peyronies with amino acid supplementation?
If the complete amino acid profile is too expensive, wouldn't a test for just lysine, proline, glycine, valine, and alanine do?
Is Peyronies incidence higher among vegetarians than among meat-eaters?
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goodluck

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Re: Amino acid testing and therapy
« Reply #15 on: August 26, 2012, 01:26:34 PM »

Thanks for reminding us of this post.  It is well written and as you say refressing.  I will add he  also took Vit C with the Lysne as it is a nessisary cofactor.

I had my AA testing done at a major hospital in Boston and it was covered by insurance.  It was not done for peryronies but for another issue I am dealing with that is more serious.
I am not sure if insurance would cover it for peyronies.

I know you can get AA tesing done online through labs like Metametrix, Genova, Doctors Data etc.
You just have to pay with a credit card.
I believe it is also know as organic acid testing.
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