Energy in Crisis
To see if the strikingly different effects of the two lipoic acid enantiomers observed in isolated mitochondria would also be seen in living organisms, the scientists tested two forms of lipoic acid in animals undergoing a simulated heart attack 69 It's in these critical moments, when the heart is starved for life-giving oxygen and the fuels in the bloodstream, and when free radicals roar through the cells as oxygen floods back in, that the production of energy can spell the difference between life and death - both for the cells of the heart, and for the living body that they support.
By opening up the chests of unconscious lab animals, the research team was able to first cut off, and then reintroduce, the heart's supply of blood - which is exactly what happens in a heart attack. And by infusing the hearts with one of the two forms of lipoic acid, they were then able to see how they would affect the mitochondria's ability to maintain energy production in the crisis and get the heart pumping blood again.
When the animals' hearts' blood supply was cut off, the flow of blood to the aorta dropped like a rock. As blood and oxygen came back online, the hearts of control animals (those whose hearts had not been provided with either form of lipoic acid) crept up slowly and weakly, and were only able to pump half as much blood into the aorta as they had before the "heart attack." But when the animals' hearts were infused with R(+)-lipoic acid, a "much steeper increase of aortic flow" resulted, along with a more complete recovery of heart function, so that their hearts were pumping 36% more blood than animals not given lipoic acid.
By contrast, the same amount of the S(-)-enantiomer yielded no benefit, so that blood flow recovered no more quickly or completely than in the controls. R(+)- but not S(-)-Lipoic Acid Helps Heart Function Recover.
In fact, in later tests, the scientists found that while R(+)-Lipoic Acid was able to improve blood flow into the aorta at extremely low concentrations, it took a dose of the S(-)-enantiomer which was as much as twenty times as great to provide any significant advantage over no treatment at all - and even then, the benefit of the S(-)-form was still less than was seen at the twentyfold lower concentration of R(+)-lipoic acid!69
Deep down in the mitochondria, the contrast was even more profound. When the scientists isolated the mitochondria from the animals' hearts after the "heart attack," having infused the hearts of different animals with different concentrations of either R(+)- or S(-)-lipoic acid, they found that mitochondrial energy production was boosted at even tiny concentrations of R(+)-lipoic acid, and continued to climb as the dose was increased. By contrast, no amount of the S(-)-form was found sufficient to increase the production of ATP.
But if the S(-)-enantiomer was unable to jumpstart mitochondrial energy production at any concentration, then how did it manage the weak increase in blood flow seen in the animals infused with extremely high levels of the compound? To answer this question, you have to understand that under certain conditions, the complex V turbine can actually be made to run in reverse, tearing down ATP to make the low-energy carrier molecule, ADP. When this happens, the mitochondria actually consume ATP more than they make, so that the cell loses the very energy the mitochondria are supposed to be producing.
So how did the two forms of lipoic acid affect this potentially disastrous tendency? By now, you've probably got a pretty good guess. At realistic concentrations, R(+)-Lipoic Acid slowed down the tendency of mitochondria to cannibalize their own ATP; by contrast, the S(-)-enantiomer accelerated it. 69 The same effect had previously been seen in the isolated, "inside-out" mitochondria. 11 But at the extremely high concentrations of the S(-)-form at which a small benefit to blood flow was seen, the pattern reversed itself, so that at these ultrahigh levels the R(+)-enantiomer no longer inhibited the teardown of ATP, while the S(-)-form began to do so.
If you're thinking that this means that the S(-)-enantiomer might actually benefit you, if you could only take enough of it - or that you'll lose one of the advantages of R(+)-Lipoic Acid if you take too much of it - think again. The concentrations that were needed to achieve this curious inversion were dozens of times greater than those achieved in humans after injecting them with 1200 mg of racemate lipoic acid. 24 In a nutshell, this is a property of the S(-)-enantiomer you're never going to get from a supplement in the real world.