Mitochondria-derived methylmalonic acid, a surrogate biomarker of mitochondrial dysfunction and oxidative stress..., 2020, Wang et al

Andy · Oct 10, 2020

Full title: Mitochondria-derived methylmalonic acid, a surrogate biomarker of mitochondrial dysfunction and oxidative stress, predicts all-cause and cardiovascular mortality in the general population

Background
Inherited methylmalonic acidemia is characterized by mitochondrial dysfunction, oxidative stress, and damage of mitochondria-rich organs in children. It is unclear whether methylmalonic acid (MMA) is related to poor prognosis in adults. The study aims to investigate the associations of MMA with all-cause and cause-specific mortality in the general population.

Methods
Overall, 23,437 adults from the US National Health and Nutrition Examination Survey (NHANES) were enrolled. NHANES 1999–2004 and 2011–2014 were separately used as primary and validation subsets (median follow-up 13.5 and 2.8 years, respectively). Circulating MMA was measured with gas chromatography/mass spectrophotometry. Hazard ratios (HR) were estimated using weighted Cox regression models.

Results
During 163,632 person-years of follow-up in NHANES 1999–2004, 3019 deaths occurred. Compared with participants with MMA <120 nmol/L, those with MMA≥250 nmol/L had increased all-cause and cardiovascular mortality in the multivariable-adjusted model [HR(95%CI), 1.62 (1.43–1.84) and 1.66 (1.22–2.27), respectively]. The association was especially significant among participants with normal cobalamin. MMA remained an independent predictor of all-cause mortality occurring whether within 5-year, 5–10 years, or beyond 10-year of follow-up (each p for trend≤0.007). That association was repeatable in NHANES 2011–2014. Moreover, baseline MMA improved reclassiﬁcation for 10-year mortality in patients with cardiovascular disease (net reclassification index 0.239, integrated discrimination improvement 0.022), overmatched established cardiovascular biomarkers C-reactive protein or homocysteine.

Conclusions
Circulating level of mitochondrial-derived MMA is strongly associated with elevated all-cause and cardiovascular mortality. Our results support MMA as a surrogate biomarker of mitochondrial dysfunction to predict poor prognosis in adults. The biological mechanisms under cardiovascular disease warrant further investigation.
Click to expand...

Open access, https://www.sciencedirect.com/science/article/pii/S2213231720309460

Midnattsol · Oct 10, 2020

Like I needed more things to complicate my B12 interest.

A problem from the abstract is that "normal" levels of B12/cobalamin does not necessarily mean "adequate" levels of B12. Functional deficiency is diagnosed based on increased MMA levels when B12 is within the normal range. And "normal" is defined differently in different countries.

I assume there are clarifications in the paper itself but based on the abstract I'm reading "people with problems in B12 metabolism have increased all-cause mortality", which aligns with studies on high levels of B12 (they could be high because people who struggle to metabolize B12 simply keep more of it in their blood?).

Kitty · Oct 10, 2020

Midnattsol said: ↑

I assume there are clarifications in the paper itself but based on the abstract I'm reading "people with problems in B12 metabolism have increased all-cause mortality"
Click to expand...

I'm not sure it does? It seems to suggest that raised levels of circulating MMA may be an indicator of mitochondrial dysfunction, and that this dysfunction could be prognostic for increased mortality.

Furthermore, the increased mortality risk is still present even when participants do not have cobalamin deficiency.

Conclusions:

"Mitochondria-derived MMA is independently and robustly associated with increased all-cause and cardiovascular mortality in the general population, especially in participants with normal cobalamin. Such link extends beyond 10 years’ follow-up. Moreover, circulating MMA improves risk stratification in patients with cardiovascular disease outmatched Hcy and CRP. Our results support MMA as a surrogate biomarker of mitochondrial dysfunction more than just monitoring cobalamin deficiency. The biological mechanisms under cardiovascular disease warrant further investigation."

Arnie Pye · Oct 10, 2020

Midnattsol said: ↑

I assume there are clarifications in the paper itself but based on the abstract I'm reading "people with problems in B12 metabolism have increased all-cause mortality", which aligns with studies on high levels of B12 (they could be high because people who struggle to metabolize B12 simply keep more of it in their blood?).
Click to expand...

You might find this (open access) paper of interest on the subject of high vitamin B12.

Title : The pathophysiology of elevated vitamin B12 in clinical practice

Link : https://academic.oup.com/qjmed/article/106/6/505/1538806

In my own case my B12 is high simply because I supplement rather a large dose. High levels caused by supplementation are not known to be dangerous.

Creekside · Oct 10, 2020

Midnattsol said: ↑

Like I needed more things to complicate my B12 interest.
Click to expand...

Just think about all the parts about B12 metabolism that researchers haven't even discovered yet.

Log in or Sign up

Mitochondria-derived methylmalonic acid, a surrogate biomarker of mitochondrial dysfunction and oxidative stress..., 2020, Wang et al

Andy Committee Member

Midnattsol Moderator Staff Member

Kitty Senior Member (Voting Rights)

Arnie Pye Senior Member (Voting Rights)

Creekside Senior Member (Voting Rights)

Share This Page

Log in or Sign up

Mitochondria-derived methylmalonic acid, a surrogate biomarker of mitochondrial dysfunction and oxidative stress..., 2020, Wang et al

Andy Committee Member

Midnattsol Moderator Staff Member

Kitty Senior Member (Voting Rights)

Arnie Pye Senior Member (Voting Rights)

Creekside Senior Member (Voting Rights)

Share This Page

Useful Searches