Cleveland Heart Lab Panel Questions

[Plumster]

A few months ago, I got the Cleveland Heart Lab basic panel and there were a couple of labs that were out of range. Unfortunately, with the pandemic, I still haven't been able to speak with my doctor about my labs. So I am wondering if anyone knows whether to worry and/or what to do about these two labs that I got. I did look in our Wiki, but did not find much info specific to these markers.

HDL-P (a predictor of cardiovascular disease): 29.2 umol/L
(Relative risk: Optimal >32.8; Moderate 29.2-32.8; High <29.2 umol/L. Reference range is 21.1-43.4)

ADMA (Asymmetric dimethylarginine) 100 H <100 (ng/mL)
From our Wiki: "Chemical found in blood plasma. Raised levels of ADMA seem to be associated with adverse human health consequences for cardiovascular disease, metabolic diseases, and also a wide range of diseases of the elderly. ADMA's role has been linked with elevated levels of homocysteine."

My homocysteine is 5.5. All other labs on the Cleveland Heart Lab basic panel are optimal. Are these above labs possibly due to being e4? Or is there something specific I can do about them?

Thanks!

[MicheleCC]

I did look in our Wiki, but did not find much info specific to these markers.
HDL-P (a predictor of cardiovascular disease): 29.2 umol/L
(Relative risk: Optimal >32.8; Moderate 29.2-32.8; High <29.2 umol/L. Reference range is 21.1-43.4)
ADMA (Asymmetric dimethylarginine) 100 H <100 (ng/mL)
From our Wiki: "Chemical found in blood plasma. Raised levels of ADMA seem to be associated with adverse human health consequences for cardiovascular disease, metabolic diseases, and also a wide range of diseases of the elderly. ADMA's role has been linked with elevated levels of homocysteine."
My homocysteine is 5.5. All other labs on the Cleveland Heart Lab basic panel are optimal. Are these above labs possibly due to being e4? Or is there something specific I can do about them? Thanks!

Hi Plumster, I am not familiar with these markers, so I looked them up on the Cleveland Heart Lab website. Here is link to what I found in the way of "patient info." https://www.clevelandheartlab.com/wp-co ... ePager.pdf with additional information on their other test markers here https://www.clevelandheartlab.com/provi ... e-science/.

As for HDL-P, I didn't see anything in particular on the Cleveland Heart Lab site, but found this on LabCorp's website:
"HDL-P, a measurement of total HDL particle number concentration, may be a better marker of residual risk than chemically measured high-density lipoprotein cholesterol (HDL-C, the so-called “good” cholesterol) or apolipoprotein A-1 (apoA-1, the major protein on HDL), ie, there may be a more consistent inverse association between cardiovascular endpoints and HDL-P compared with HDL-C.
Direct quantification of HDL-P concentration by NMR may be useful to refine cardiovascular risk and to evaluate novel HDL-directed therapies. Further studies are needed to clarify the role of HDL-P in clinical practice."

Have you browsed the Cleveland Heart Lab website? There's good information for both practitioner and patient. Hope this is helpful to you!

[Plumster]

Hi Plumster, I am not familiar with these markers, so I looked them up on the Cleveland Heart Lab website. Here is link to what I found in the way of "patient info.

Thank you! It didn't even occur to me to go to their site!

Hm, so they provide lifestyle recs, but I am already doing them....

[Magda]

A few months ago, I got the Cleveland Heart Lab basic panel and there were a couple of labs that were out of range. Unfortunately, with the pandemic, I still haven't been able to speak with my doctor about my labs. So I am wondering if anyone knows whether to worry and/or what to do about these two labs that I got. I did look in our Wiki, but did not find much info specific to these markers.

HDL-P (a predictor of cardiovascular disease): 29.2 umol/L
(Relative risk: Optimal >32.8; Moderate 29.2-32.8; High <29.2 umol/L. Reference range is 21.1-43.4)

ADMA (Asymmetric dimethylarginine) 100 H <100 (ng/mL)
From our Wiki: "Chemical found in blood plasma. Raised levels of ADMA seem to be associated with adverse human health consequences for cardiovascular disease, metabolic diseases, and also a wide range of diseases of the elderly. ADMA's role has been linked with elevated levels of homocysteine."

My homocysteine is 5.5. All other labs on the Cleveland Heart Lab basic panel are optimal. Are these above labs possibly due to being e4? Or is there something specific I can do about them?

Thanks!

Plumster,

Here are a few important points, I hope you will find helpful, in understanding ADMA and ADMAs formation/removal.

Asymmetrical dimethylarginine (ADMA) inhibits Nitric Oxide and angiogenesis

ADMA forms from amino acid Arginine (Arg) under the actions of the enzyme called methionine-dependent protein arginine N-methyltransferase (PRMT). ADMA is formed my methylation of arginine residues of nuclear proteins (like histones). This reaction requires SAMe and is inhibited by copper, histone acetylation, homocysteine, ellagic acid (walnuts, pecans strawberries, grapes).

Then ADMA residues are separated from the protein and released into the blood where ADMA binds to Nitric oxide synthesis (NOS) enzyme, slowing its activity in Nitric Oxide (NO) formation, thus regulating the rate of NO synthesis [1]. This explains ADMAs negative effects on endothelium function.

A principal mechanism regulating concentration of ADMA is through action of enzyme dimethylarginine dimethylaminohydrolase (DDAH) that degrades ADAM to citrulline (how is your urea cycle, BUN status, and in general amino acid intake?).
Side note: amino acid citrulline and aspartic acid are united to produce arginosuccinate Then the degradation of arginosuccinate to fumarate and arginine is a primary mechanism for sustain plasma levels of arginine.

A degradation of ADMA to citrulline requires zinc. It is inhibited by angiotensin II, arginine, glucose…

DDAH is susceptible to damage by cellular oxidation, hence antioxidants have protective function and allow normal ADMA removal, and normal NO formation. Think ascorbic acid, all trans retinoic acids (VitA), EGCG, Vitamin E.

ADMA formation is increased my methionine loading producing endothelial dysfunction. Again
effects can be reversed by supplementation with ascorbic acid (Vitamin C) and Vitamin A (retinol) and normalization of homocysteine levels.

In summary [1]:
- L-Arginine stimulates NO synthesis to overcome the inhibitory effects of high ADMA. Low-fat meals help to reduce the synthesis of ADMA by PRMT.
- Vitamin A induces expression of DDAH, causing lowering of ADMA
- Antioxidants prevent the inhibition of DDAH, thus enhancing the removal of ADMA
- Normalization of elevated homocysteine with B6, B12, B9 reduces ADMA by controlling endothelia oxidative effects.
- Individuals with persist ADMA elevation may benefit with hormonal interventions such as acetylcholinesterase inhibitors and natural estrogen replacement therapy and ACE inhibitors. Estradiol enhances DDAH activity [1]
- ADMA levels rise after a high fat meal and may contributes to abnormal blood flow found in DM and atherogenesis. https://www.ahajournals.org/doi/full/10 ... .20.9.2039
- Exercise has a strong positive effect in the arginine /ADMA ratio.
- The inhibitory effects of ADMA on NO production may be overcome with the use of supplemental arginine [1] Side note very careful with this: Arginine supplementation depends on glutamine status. Supplementation with citrulline and aspartic acid should be considered.
High Arg increases ammonia!

I hope this helps!

Magda

[1] Lord R. Laboratory Evaluations for Integrative and Functional Medicine.

[Plumster]

Plumster,

Here are a few important points, I hope you will find helpful, in understanding ADMA and ADMAs formation/removal.

Wow, thank you so much for taking the time to explain, Magda! I really appreciate it, as I always prefer to understand the mechanisms at work. I can't say I've understood your account fully, but I did come to the realization that my low stomach acid (due to my CIRS?) has likely given me an amino acid deficiency. And in a vicious cycle, I have slowly cut back on protein because of the stomach discomfort that follows. But I'll be sure to increase protein and continue to take sufficient betaine HCL with pepsin.

Were you the one who pointed out that my low homocysteine, yet high mma were probably related to a methionine conversion problem? I think it was you (thank you!) I should talk to my doctor, too, eventually, but I'm not sure she would arrive at the same conclusion that you have without an amino acid test, and I won't be able to get a test for at least a month or probably more due to the pandemic. So, moving forward without a test I'm increasing my protein, seeds, and nuts and taking betaine.

According to Examine.com, L-Citrulline is a more efficient way to increase L-argenine in the body. The website also states alongside some studies that "Although there is some evidence for an increase in ADMA (a negative regulator of NOS that is derived from L-arginine), it does not appear to occur most of the time" with argenine supplementation. I'm already exercising and getting sufficient Vitamin A. My diet is plant based, not keto, and I get lots of antioxidants (assuming I am absorbing them). My most recent blood urea nitrogen lab result was 6 mg/dl. I don't know my glutamine status, so how do I go about supplementing citrulline and aspartic acid?

[Tincup]

I'm already exercising and getting sufficient Vitamin A. My diet is plant based, not keto, and I get lots of antioxidants (assuming I am absorbing them).

Curious about Vitamin A. I understand that some people have poor conversion of beta carotene to retinol. I started taking cod liver oil to overcome this myself.

[Plumster]

Curious about Vitamin A. I understand that some people have poor conversion of beta carotene to retinol. I started taking cod liver oil to overcome this myself.

Thanks, Tincup. While I haven't done it yet this year, I've been taking the NutrEval FMV test from Genova Diagnostics for the past two years and my Vitamin A status has always been good. I do have poor conversion, but I must be getting sufficient in my diet? This is also confirmed when I try chronometer.

[Plumster]

It appears that sun exposure improves HDL-P (and psoriasis). Study here.