Age and gender dependent bioavailability of R- and R,S-α-lipoic acid: a pilot study

Abstract

Lipoic acid (LA) shows promise as a beneficial micronutrient toward improving elder health. Studies using old rats show that (R)-α-LA (R-LA) significantly increases low molecular weight antioxidants that otherwise decline with age. Despite this rationale for benefiting human health, little is known about age-associated alterations in absorption characteristics of LA, or whether the commercially available racemic mixture of LA (R,S-LA) is equally as bioavailable as the naturally occurring R-enantiomer. To address these discrepancies, a pilot study was performed to establish which form of LA is most effectively absorbed in older subjects relative to young volunteers. Young adults (average age=32 years) and older adults (average age=79 years) each received 500 mg of either R- or R,S-LA. Blood samples were collected for 3h after supplementation. After a washout period they were given the other chiral form of LA not originally ingested. Results showed that 2 out of 6 elder males exhibited greater maximal plasma LA and area under the curve for the R-form of LA versus the racemic mixture. The elder subjects also demonstrated a reduced time to reach maximal plasma LA concentration following R-LA supplementation than for the racemic mixture. In contrast, young males had a tendency for increased bioavailability of R,S-LA. Overall, bioavailability for either LA isoform was much more variable between older subjects compared to young adults. Plasma glutathione levels were not altered during the sampling period. Thus subject age, and potential for varied response, should be considered when determining an LA supplementation regimen.

Fig. 1. Study design and HPLC separation and detection of plasma lipoic acid

Subjects received either R-LA or R,S-LA in a cross-over design (A). An indwelling catheter was placed in subject’s arm to allow blood sampling. Subjects received a 500 mg oral supplement of either R- or R,S-LA. Blood samples were collected over a 3 h time course following supplementation (A). Plasma samples were derivatized to ABD-F, separated by HPLC, and LA was monitored by fluorescence detection and quantified to standards. Shown is a typical HPLC chromatogram for an authentic R-LA standard (B). A typical chromatogram of LA detection in the plasma is shown for a subject in the study (C).

Fig. 2. Plasma LA profiles for subject groups

The line traces present each individual’s detected LA concentrations during the study.

Fig. 3. Individual pharmacokinetic parameters

C_max (A and F), T_max (B and G), t_1/2 (C and H), AUC (D and I), and MRT (E and J) are presented in the panels. The pharmacokinetic values for R- and R,S-LA from each individual subject are connected with a line in graphs A–E. Within subject variability (F–J) is presented for each pharmacokinetic parameter as a ratio of R,S-LA relative to R-LA. Points landing above the horizontal axis indicate that a greater value was observed after the subject took R,S-LA, while points landing below the horizontal axis indicate that a greater value was observed after the subject took R-LA. The horizontal line indicates no difference between the two forms.