Differential Effect of Alpha-lipoic Acid on Healthy Peripheral Blood Lymphocytes and Leukemic Cells
Orthomolecular Medicine, 2008, 23(2):83-89
This article is available at: http://www.orthomed.org/jom/jom.html
A pre-published version is available at: http://www.bcrionline.org/articles/89024823_pre.pdf
Mikirova N, Jackson J, Riordan N
Lipoic acid (LA), also known as alpha-lipoic acid, is a sulfur-containing fatty acid. It is found inside every cell of the body, where it helps to regenerate the energy that keeps cells alive and functioning. LA is an alipoamide and is a constituent of biological membranes and an important cofactor of mitochondrial dehydrogenases. LA is a key part of the machinery that turns glucose into energy.
LA, unlike other antioxidants that work only in water or fatty tissues, functions in both water and fat. This gives LA a broad spectrum of antioxidant actions. A healthy body makes enough LA to supply its own requirements. However, several medical conditions may be accompanied by low levels of LA.
LA is easily absorbed from the diet. It enters cells from the bloodstream and is readily converted to its reduced form, dehydrolipoic acid (DHLA). Both LA and DHLA act as antioxidants in vitro and in vivo [1-5].
The specific effects of LA and DHLA include quenching of reactive oxygen species, such as superoxide radicals and hydroxyl radicals, and chelation of copper, zinc, and iron. It is important in the intracellular recycling of vitamin E through interaction with vitamin C. LA also increases levels of glutathione, a very important antioxidant normally found in cells [6].
This powerful antioxidant is currently being studied to provide both preventive and therapeutic benefits in numerous conditions such as diabetes, heart disease, and neurological diseases (Parkinson’s and Alzheimer’s) [7-15]. For example, LA has been used for decades to treat diabetic peripheral neuropathy. Free radicals (oxidants) are thought to play a role in neuropathy. It has been shown that LA is effective in the prevention of early diabetic glomerular injury and has advantages over high doses of other antioxidants [13].
Although hundreds of studies over the past years showed how LA energizes metabolism, our studies focused on a new aspect. We analyzed the differential effect of LA on energy metabolism of normal lymphocytes and leukemic lymphocytes and demonstrated inhibition of the energy metabolism of leukemic cells in comparison with normal cells. Analysis was performed for three leukemic cell lines and lymphocytes of healthy subjects. At similar concentrations, lipoic acid was toxic to leukemia cells and non-toxic to blood lymphocytes. Exposure of cells to 200-800 uM of LA was followed by a decrease of ATP production and increased apoptosis of leukemia cells. These experiments may be useful to prove the effectiveness of lipoic acid in the treatment of leukemia.
In addition, we demonstrated that supplementation of lymphocytes under oxidative stress can restore the functional activity of cells and improve the level of mitochondrial functioning and mitochondrial potential. The experiments suggest that lipoic acid has a beneficial effect in pathological conditions involving impairment of the immune system due to oxidative stress.
