Plasma concentration, urinary excretion and renal clearance of L-carnitine during pregnancy: a reversible secondary L-carnitine deficiency

Abstract

Plasma concentration, urinary excretion and renal clearance of free, total and esterified L-carnitine were monitored monthly in 14 women during the last 6 months of pregnancy and 1 month after delivery. Plasma concentration and renal clearance measured 1 month after delivery overlapped with normal values for females of comparable age, and were considered the reference values for further comparisons. Plasma concentration of free, total and esterified L-carnitine decreased during pregnancy, reaching values as low as half of those measured 1 month after delivery, whereas urinary excretion and renal clearance, mainly of L-carnitine esters, increased, with renal clearance reaching a peak at the 16th week of pregnancy. Pregnancy thus leads to a reversible secondary deficiency of L-carnitine. The involvement of L-carnitine in the excretion of an excess of acyl-S-coenzyme A groups to prevent a possible systemic acidosis, as well as hormonal changes and a reduction of L-carnitine biosynthesis, could play a significant role in the variations in L-carnitine metabolism encountered in pregnancy. As physiological components of L-carnitine are excreted via a saturable tubular reabsorption, their threshold seems to follow plasma concentration, even when they decrease markedly, as in pregnancy.

Carnitine status of pregnant women: effect of carnitine supplementation and correlation between iron status and plasma carnitine concentration

“…The present study agrees with other studies ((Bargen-Lockner et al, 1981;Cederblad et al, 1985Cederblad et al, , 1986Genger et al, 1988;Marzo et al, 1994;Schoderbeck et al, 1995;Cho et al, 2003) in showing that plasma carnitine concentrations in women markedly decline during pregnancy. In our study, plasma Table 3 Concentration of g-butyrobetaine and 6-N-trimethyllysine in plasma of women receiving either a L-carnitine supplement (500 mg per day) or a placebo from the 12th week of gestation until delivery at various time points Table 2 Concentration of total carnitine, free carnitine and carnitine esters in plasma of women receiving either a L-carnitine supplement (500 mg per day) or a placebo from the 12th week of gestation until delivery at various time points carnitine concentration at delivery in the placebo group was approximately 40% lower than that at week 12 of pregnancy.…”

“…Physiologically, plasma carnitine concentrations are strongly controlled by the renal excretion of carnitine (Rebouche and Seim, 1998). It has been found that urinary excretion of carnitine even declines during pregnancy and paralleled plasma carnitine concentrations (Cederblad et al, 1986;Marzo et al, 1994). Therefore, an increased renal excretion of carnitine can be ruled out as a possible reason for the low plasma carnitine concentrations during late pregnancy.…”

“…Plasma carnitine concentrations, however, decrease in women during gestation. At the time of delivery, plasma carnitine concentrations decrease to about half of the concentrations of non-pregnant women (Bargen-Lockner et al, 1981;Cederblad et al, 1985Cederblad et al, , 1986Genger et al, 1988;Marzo et al, 1994;Schoderbeck et al, 1995), even though dietary carnitine intake increase, as gestation proceeds (Cho et al, 2003). Similar low carnitine concentrations are only found in patients with carnitine deficiency (Duran et al, 1990).…”

Abnormal Newborn Screening in a Healthy Infant of a Mother with Undiagnosed Medium-Chain Acyl-CoA Dehydrogenase Deficiency

“…The decrease in total carnitine is mainly caused by a decrease in free carnitine (Schoderbeck et al 1995) and is thought to be the consequence of a reduced rate of carnitine biosynthesis, possibly because of an inadequate iron status (Keller et al 2009) or because of a low availability of precursors for carnitine (Ringseis et al 2010). Interestingly, one study reported a complete normalization of plasma carnitine one month after delivery (Marzo et al 1994), and our finding of low-normal free carnitine 16 days after delivery may reflect a partial normalization to concentrations often seen in patients with MCADD.…”

The neural stem cell/carnitine malnutrition hypothesis: new prospects for effective reduction of autism risk?

“…Although all of those studies involve children, and our mouse studies document NSC derangements in imposed in mid-gestation, the clinical data are nonetheless consistent with the carnitine deficiency hypothesis. In that regard, multiple studies document significant decreases in maternal serum carnitine levels during pregnancy that approach pathologically low levels (52)(53)(54)(55)(56)(57)(58)(59). Interestingly, that decline in carnitine levels commences at the onset of mid-gestation (12 weeks, 58,59), a window that corresponds to the one where we interfere with carnitine synthesis and fatty acid ␤-oxidation in our mouse in utero electroporation experiments (34).…”