Thanks for that. Aren't these the concepts behind some of the
Cyrex panels like 'Neurological Autoimmune Reactivity Screen - Expanded' and 'Multiple Food Immune Reactivity Screen' (oddly the latter appears to be more comprehensive than the same array '90x')?
The paper doesn't mention AGEs since it has a different legitimate focus.
It's frustrating not to have time to go deep, but I find some more interesting titles:
2015
Oral L-carnitine supplementation increases trimethylamine-N-oxide but reduces markers of vascular injury in hemodialysis patients
Conclusions:
This study demonstrated that although oral L-carnitine supplementation was associated with increased TMAO levels, it might be beneficial on vascular injury in patients on HD. Vasculoprotective properties of L-carnitine supplementation in HD [hemodialysis] patients might be ascribed partly to its inhibitory actions on AGE. [Emphasis added]
I'm not sure how the context of hemodialysis affects things here, but
it's interesting that the researchers suggest that low AGEs may modify the effects of TMAO. This goes back to my point. In the studies showing independent and dose dependent relationships between high TMAO and CVD risk, have they included a cohort on a low AGE diet? At the same time, if carnitine inhibits AGE, then why are high meat diets associated with high AGEs? Maybe the cooking methods override carnitine's protective effect? Then why not in the study of HD patients? Totally confusing.
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These next three papers all seem to report different aspects of the same
small study of 20 people. (Have I not read warnings about studies with too many endpoints?)
July 2018 (n=20?)
L-Carnitine Supplementation Increases Trimethylamine-N-Oxide but not Markers of Atherosclerosis in Healthy Aged Women
Results:
L-carnitine supplementation elevated fasting plasma carnitine in the mid-point of our study and it remained increased until the end of supplementation period. Moreover, it induced tenfold increase in plasma TMAO concentration but did not affect serum C-reactive protein, interleukin-6, tumour necrosis factor-α, L-selectin, P-selectin, vascular cell adhesion molecule-1, intercellular adhesion molecule-1 or lipid profile markers.
June 2019 (n=20)
Plasma Trimethylamine-N-oxide following Cessation of L-carnitine Supplementation in Healthy Aged Women
During this period, no modifications in serum lipid profile and circulating leukocyte count were noted.
Sep 2019 (n=20)
Increased Trimethylamine N-Oxide Is Not Associated with Oxidative Stress Markers in Healthy Aged Women
... there were no significant changes in serum ox-LDL, myeloperoxidase, protein carbonyls, homocysteine, and uric acid concentrations due to supplementation. Significant reduction in white blood cell counts has been observed following 24-week supplementation, but not attributable to L-carnitine. Our results in healthy aged women indicated no relation between TMAO and any determined marker of oxidative stress over the period of 24 weeks
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I confess that I
want to think that despite the barrier/antigen issues and the TMAO/CVD risk issues, that actual individual outcomes of a diet higher in animal protein are, like everything else, context dependent. I'm not sure we can just look at the broad strokes and make assumptions about what's happening in an individual's body. The studies above suggest some markers to investigate if one is eating this way, although some probably aren't readily available and I'd like to better understand why some were chosen:
Markers of Atherosclerosis
serum C-reactive protein
interleukin-6
tumour necrosis factor-α
L-selectin
P-selectin
vascular cell adhesion molecule-1
intercellular adhesion molecule-1
lipid profile markers
leukocytes
Markers of Oxidative Stress
serum ox-LDL
myeloperoxidase
protein carbonyls
homocysteine
uric acid
At the same time, when I read that TMAO affects lipid metabolism, and knowing that ApoE4 also does, then I sure wonder about compounding issues there.
My predicament is that I am doing better eating more animal protein but also test high for serum TMAO along with chronically elevated hsCRP. The latter could be due to chronic bursitis in at least eight bursas, but apparently the contribution of this sort of tissue issue to hsCRP hasn't been studied. I've stopped betaine and choline supplementation to assess their contributions to the high TMAO.