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guys using geronovas r-ala

wasp

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Kilo Klub Member
Joined
Nov 19, 2009
Messages
1,172
got a guy on another forum telling me na-r-ala is much better , and this can be had at half the cost of geronovas r-ala

Baseline levels of RLA (Limit of Detection ~50-250 ng/mL) could be detected by liberation from plasma proteins with mobile phase using a modification of the method of Chen et al. (46) Although previous studies indicate rac-LA does not accumulate in blood or tissues, (17) in the present study baseline RLA was detected only in subjects who are regular users of a mixture of RLA and R-DHLA, even subsequent to a three-day washout period at levels of 0.05-0.25 mcg/mL. Analysis of the plasma concentration-time curves in a preliminary study with two subjects revealed that 600 mg pure RLA yields low Cmax and bioavailability (as measured by AUC) values, significantly lower than an equivalent weight of rac-LA. (43) The preliminary study provided the first published PK values for NaRLA. The Cmax and AUC values for NaRLA in the male subject were 25.86 and 3.3 times higher, respectively, than RLA. In the female subject, NaRLA produced Cmax and AUC values 17.9 and 2.67 times higher, respectively, than pure RLA. (43) RLA (100 mg; commonly found in nutritional supplements) is barely distinguishable from baseline, presumably due to poor absorption (data not shown). As expected, use of RLA as the pre-dissolved sodium salt resulted in significant increases in Cmax and AUC in all 12 subjects (Figure 2; Table 2). The average dose was 8.25 mg/kg, generating a mean Cmax of 16.03 mcg/mL (range: 10.6-33.8 mcg/mL), median Tmax of 15 minutes (range: 10-20 minutes), and mean AUC of 441.59 mcg min/mL (7.36 mcg hr/mL). The plasma concentration time profile had negligible effect on plasma glucose levels measured at each time point. Subject 3 consumed three 600-mg doses of RLA (as NaRLA) (Figure 3), resulting in a Cmax of 21.9 mcg/mL, AUC of 1,049 mcg min/mL (17.48 mcg x hr/mL), and extended the Tmax out to 45 minutes. An unexpected finding of this study was that, at plasma concentrations as high as 30 mcg/mL (~150 [micro]M) (Cmax subject 6), negligible free RLA was detected.


Discussion

Although the clinical significance of baseline RLA (0.05-0.25 mcg/mL) is not fully characterized, previous trials have correlated low baseline RLA with a variety of disease states. (7,10,49-52) It has been suggested that the presence of RLA in plasma may function to maintain the plasma redox status, which shifts to a more oxidized state with age and in numerous diseases. (53,54) The current study and previous findings from this laboratory conclude that pure RLA is not suitable for use in nutraceutical or pharmaceutical products. Rather, it should be treated as raw material for further processing into stable, bioavailable dosage forms. PK data reveals pure RLA is significantly less bioavailable than RLA found as a 50-percent component of rac-LA; and RLA in a salt form is considerably more bioavailable than an equivalent dose of racLA (RLA + SLA). This indicates SLA may function as a competitive inhibitor in the absorption of RLA.

Different forms of RLA produce dramatically different PK values. Recently, RLA was compared to NaRLA in humans using a simple crossover design. (43) This study compared Cmax and AUC values of a pre-dissolved aqueous solution containing 600 mg RLA (as NaRLA) to those of 600 mg RLA in the same subjects. In a single male (subject 1), NaRLA produced Cmax of 14.1 mcg/mL; whereas, RLA resulted in a Cmax of 0.7 mcg/mL (increase of 25.86x). The AUC in the same subject was 5.18 mcg hr/mL for NaRLA versus 1.56 mcg hr/mL for RLA (increase of 3.3x). In a single female (subject 4), Cmax was 18.1 mcg/mL for NaRLA versus 1.01 mcg/mL for RLA (increase of 17.9x) and the AUC was 5.71 mcg hr/mL for NaRLA compared to 2.14 mcg hr/mL for RLA (increase of 2.67x).

The data shows Cmax and relative bioavailability as measured by AUC for the aqueous solution of three doses of 600 mg RLA (as NaRLA) taken at 15-minute intervals is similar to those reported for a 20-minute I.V. infusion of 300 mg rac-LA. (55) Cmax and AUC values were significantly increased over the one-time dose. Cmax values reached 21.9 mcg/mL versus 12.9 mcg/mL and AUC values increased from 376.2 mcg min/mL (6.27 mcg hr/mL) to 1,049 mcg min/mL (17.48 mcg min/mL).

Based on the mean values from eight human PK studies utilizing 600 mg rac-LA, the current authors suggest the threshold of activation of the therapeutic effects of LA is equal to Cmax of 4-5 mcg/mL (~20-25 [micro]M) and AUC equal to 2.85 mcg hr/mL. (17,45,46,55-59) More consistent therapeutic results may be achieved at plasma concentrations of 10-20 mcg/mL (~50-100 [micro]M) of the natural enantiomer, RLA. (17,60) The upper limit of the human therapeutic concentration range is ~50 mcg/mL (~250 [micro]M). (41)

A basic principle of pharmacology states that free drug (not bound to plasma proteins) is more biologically active than plasma protein-bound drug and mostly responsible for the therapeutic action. (61-63) Most PK studies and assays for LA have measured the total LA content in serum or plasma rather than differentiating the concentrations of free and bound LA. Many different techniques with varying degrees of efficiency have been utilized to determine the total LA concentrations. In vitro, rac-LA spiked into human plasma is not measurable in "free" form until plasma protein binding is saturated at ~4-5 [micro]M (0.825-1.030 mcg/mL). (64) In rats, it was reported only 20 percent (~0.8 mcg/mL) of the total plasma RLA (~4 mcg/mL) was free (using the Centrisart ultrafiltration device). The level of free/unbound RLA was concentration independent and temperature dependent. The "free" value corresponded to the amounts of RLA found in skeletal muscle by micro-dialysis and was extrapolated to account for plasma protein binding in humans. (17) Since the therapeutic efficacy of a compound is associated with the "free" levels and levels of "free" drug concentration differ from species to species (and even wide inter-individual differences are known), the decision was made to test the levels of "free" RLA in each subject's plasma.

This is the first study to demonstrate negligible amounts of "free" RLA, even at Cmax. This indicates that a re-assessment of a fundamental principle of pharmacology (i.e., the therapeutically active form of a drug or nutrient is correlated to the amount of "free" versus unbound drug) relative to the mechanisms of transport and action of LA is necessary.
 

wasp

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Kilo Klub Member
Joined
Nov 19, 2009
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1,172
but , in fact geronova is na-r-ala

* Bio-Enhanced® R-Lipoic Acid (as Na-RALA) is heat and shelf stable, highly soluble and has proven to be the most bioavailable oral form of lipoic acid on the market.

* Bio-Enhanced® RLA is significantly more bio-available than the ‘free-acid’ form of R-Lipoic Acid (RLA). In a preliminary human pharmacokinetic trial, the maximum plasma concentration was 40 times higher than that of unstabilized RLA.

* Bio-Enhanced® RLA is made by a proprietary process which removes all traces of residual solvents, a significant problem in unstabilized RLA products.

* Bio-Enhanced® RLA does not cause heartburn, indigestion or stomach discomfort, which can occur with unstabilized RLA.

* Bio-Enhanced® R-Lipoic Acid is a quick release product, attaining high plasma levels rapidly.

* Bio-Enhanced® R-Lipoic Acid is much more stable than RLA even at elevated temperatures. Heated to over 150° C for 6 hours there is no loss of activity, and polymer formation was undetectable. Pure RLA would instantaneously polymerize under these conditions.

* Bio-Enhanced® R-Lipoic Acid requires no refrigeration and does not polymerize, whereas RLA polymerizes at temperatures slightly above ambient. The polymerization of RLA is accelerated by light, heat and moisture.


Note: The R-Lipoic Acid in Bio-Enhanced® R-Lipoic Acid is stabilized with Na (sodium). However, one serving contains less than 1% of the Daily Value for sodium, an insignificant contribution to dietary sources. The sodium in this product is unlikely to affect blood pressure levels.
 

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