Research emanating from the Linus Pauling Institute at Oregon State University and published in the Archives of Biochemistry and Biophysics has shown that dietary supplementation with lipoic acid lowered plasma triglyceride levels up to 60 percent in rats. While the extent of the effect is yet to be determined in humans; if similar, lipoic acid could be considered to be as effective in this regard as certain prescription medications.

Triglycerides are what the body converts dietary fat into in the intestines so that it can be transported in the bloodstream (packaged with cholesterol and proteins to form chylomicrons, which emulsify in the blood to be transported to the tissues for energy production and storage). It is believed that the fatty buildup in the arteries known as atherosclerosis can be attributed in part to the levels of triglycerides in the bloodstream.

In this experiment, it was found that lipoic acid supplementation dramatically reduced the amount of circulating triglycerides via two pathways – it increased the rate at which they were removed from the blood, and it reduced the production of triglycerides in the liver by reducing the number of enzymes that synthesize them.

Lipoic acid has also been shown in cell culture experiments to increase the cellular uptake of glucose by recruiting the glucose transporter GLUT4 to the cell membrane; and of course, rat aging studies have suggested that the use of L-carnitine and lipoic acid in combination results in improved memory performance and delayed structural mitochondrial decay.

According to the press release, the amount of lipoic acid supplementation used in these experiments would equate to about two grams per day for a 150-pound (68 kg) person (the article claims 200mg/kg for the rats, so they’re dividing by a factor of 8 to account for metabolic differences between rats and humans). Also of note is their use of R-alpha-lipoic acid (not the S enantiomer or the racemate).

Personally, I take the sodium salt of r-alpha-lipoic acid (Na-RALA), but nowhere near the 2g/day recommended here… more like 600mg/day. At the current price of about USD 1/gram for the bulk powder, such a regimen seems a bit expensive.

L-carnitine is a naturally occurring compound which is primarily located in mitochondria and possesses potential protective effects against many mitochondrial toxic agents. It is derived from two sources: endogenous synthesis, in the liver and kidney, and from exogenous dietary sources such as red meat and dairy products. L-carnitine is an essential cofactor for the translocation of long chain fatty acids from the cytoplasmic compartment into mitochondria, where beta-oxidation enzymes are located for ATP production.

To test their hypothesis, the researchers studied a rat model of hepatocarcinogenesis under conditions of carnitine deficiency and supplementation.

L-carnitine supplementation resulted in a complete reversal of the cancer-related changes in the rats’ livers.

Given these promising results, they intend to conduct further investigations into the mechanisms behind carnitine’s anti liver cancer effect.

Carnitine supplementation, particularly in the form of acetyl-L-carnitine (ALCAR), which is cheaply available from a number of suppliers, has a reasonably long history of conferring health and longevity benefits. In my opinion, it’s one of the cornerstones of an effective supplementation regime, particularly in combination with alpha lipoic acid (ALA).

In an effort to determine whether lipoic acid, which has in the past shown to affect brain tissue, might have some activity relevant to treating Alzheimer’s disease, the researchers administered LA to rats and measured its presence in their brains. LA was only found in trace amounts, indicating that it does not readily cross the blood brain barrier, and furthermore that LA’s effect on the brain must therefore be mediated by other factors, possibly due to its capacity to reactivate other circulating antioxidants.

Here’s the abstract:

Distribution study of orally administered lipoic acid in rat brain
tissues.

Brain Res. 2008 Nov 19; PMID: 19046949

Chng HT, New LS, Neo AH, Goh CW, Browne ER, Chan EC.

Department of Pharmacy, Faculty of Science, National University of Singapore, 18 Science Drive 4, 117543 Singapore.

Lipoic acid (LA), an essential cofactor for mitochondrial enzymes and a natural antioxidant, has been explored for the treatment of Alzheimer’s disease. However, lipoic acid distribution in brain has not been investigated via oral dosing in human subjects or animals. Therefore, we aim to investigate the distribution of orally administered LA from systemic circulation into rat brain tissues and understand the transport efficiency of lipoic acid across the blood- brain barrier. Brain and blood samples were obtained from male Lister Hooded rats at pre-defined time points after single and chronic oral dosing of LA at 50 mg/kg. Levels of LA were determined using liquid chromatography tandem mass spectrometry. An equilibrium dialysis method was employed to elucidate LA protein binding in brain and blood tissues. Basal endogenous levels of LA in control rats were found to fluctuate between 0.005 and 0.267 microM in blood and 0-0.024 microM in brain after correction for residual blood volume. Pharmacokinetic profiling demonstrated rapid biphasic elimination of LA in blood and poor distribution into various brain regions with levels ranging from 0.0009 to 0.0072 microM. The in vitro and in vivo LA brain:blood partition ratios were 0.1 and -0.01, respectively. Our results demonstrate for the first time that LA does not cross the blood-brain barrier readily and suggest that the antioxidant effect of LA in brain may not be due to its direct effect in the central nervous system.

I will be reporting on any little bit of good that can be derived from the supplements life-extensionists tend to take; so, to that end, I present the following abstract:

Alpha-Lipoic Acid Improves Acetic Acid-Induced Gastric Ulcer Healing in Rats:

To evaluate the role of ALA treatment on the healing of acetic acid-induced gastric ulcer, rats were given ALA (35 mg/kg/day) or saline for 3 days before the induction of ulcer and the treatment was continued twice daily for 2 days (early) or 10 days (late) until they were decapitated. Gastric ulcer index, microscopic score, elevated DNA fragmentation and chemiluminescence levels of the saline-treated ulcer groups were all reduced by ALA treatment. Likewise, ALA treatment inhibited chemiluminescence levels in both early and late ulcer groups. Marked reduction in glutathione levels of the saline-treated early ulcer group was reversed by ALA treatment, while ALA treatment was effective in depressing gastric myeloperoxidase activity in the late ulcer group. In conclusion, ALA treatment shows protective role in the healing of acetic acid-induced gastric injury in rats via the suppression of neutrophil accumulation, preservation of endogenous glutathione, inhibition of reactive oxidant generation and apoptosis.