Lipoic Acid

(α-)lipoic acid (LA) is popular as a supplement. We don’t need any our diet to survive; we synthesize it. It’s a precursor for necessary mitochondrial enzymes (mitochondria, roughly speaking, burn oxygen to power our bodies). It’s plausible that beefing up the subtrate of material that’s used by the enzymes can compensate for their working less efficiently with age (this has been demonstrated in rats).

Though LA has long been touted as an antioxidant, it has also been shown to improve glucose and ascorbate handling, increase eNOS activity, activate Phase II detoxification via the transcription factor Nrf2, and lower expression of MMP-9 and VCAM-1 through repression of NF-kappa B. LA and its reduced form, dihydrolipoic acid, may use their chemical properties as a redox couple to alter protein conformations by forming mixed disulfides. Beneficial effects are achieved with low micromolar levels of LA, suggesting that some of its therapeutic potential extends beyond the strict definition of an antioxidant. Current trials are investigating whether these beneficial properties of LA make it an appropriate treatment not just for diabetes, but also for the prevention of vascular disease, hypertension, and inflammation.

via. I don’t know what all that means; however, I’d suggest that since we synthesize it up to low concentrations, it’s almost certain to be useful at low concentrations :)

LA passes easily to the brain; however, it also quickly binds to protein. Unless you take enough (over 150 micromolar), it will ALL be bound to protein. So a single high dose might be needed to get any to the brain. via.

LA in vitro acts as a direct antioxidant (of ROS and RNS); also, protein-bound-LA in cells triggers natural anti-oxidant mechanisms (in a more sustained way than if free LA/DHLA were directly scavenging ROS/RNS) and reduces inflammation due to oxidative stress. via.

LA enhances mitochondrial energy metabolism and protects against diabetic neuropathy (800mg/day). It also reduces migraine and headache frequency in migraine sufferers (600mg/day). via.

LA chelates inorganic mercury (but reduces clearance of methylmercury, which is what you’re getting when you eat shark/swordfish/tuna/etc). via. You’d take it after acute inorganic mercury exposure (in a dose depending on the exposure).

LA slows the progress of Alzheimer’s dementia (ibid):

LA has been shown to have a variety of properties which can interfere with the pathogenesis or progression of AD. For example, LA increases acetylcholine (ACh) production by activation of choline acetyltransferase and increases glucose uptake, thus supplying more acetyl-CoA for the production of ACh. LA chelates redox-active transition metals, thus inhibiting the formation of hydroxyl radicals and also scavenges reactive oxygen species (ROS), thereby increasing the levels of reduced glutathione. In addition, LA down-regulates the expression of redox-sensitive pro-inflammatory proteins including TNF and inducible nitric oxide synthase. Furthermore, LA can scavenge lipid peroxidation products such as hydroxynonenal and acrolein.

Evidence for a clinical benefit for LA in dementia is yet limited. There are only two published studies, in which 600 mg LA was given daily to 43 patients with AD (receiving a standard treatment with choline-esterase inhibitors) in an open-label study over an observation period of up to 48 months. Whereas the improvement in patients with moderate dementia was not significant, the disease progressed extremely slowly (change in ADAScog: 1.2 points=year, MMSE: -0.6 points=year) in patients with mild dementia (ADAScog

This is not double-blind, but the worsening of dementia was much slower than in other long-term studies (being treated with either nothing or choline-esterase inhibitors).

(above cites found on Wikipedia)

Animals treated with alpha-lipoic acid, for example, suffered less brain damage and had a four times greater survival rate after a stroke than animals who did not receive this supplement.

Of course, jumping to sustained high doses is premature:

In my personal experience, high dosages of ALA and acetylcarnitine can cause insomnia and ALA may cause heart rhythm disturbances.

Sounds like a stimulant effect.