An article published online on February 20, 2009 in the journal Archives of Biochemistry and Biophysics reported the benefits of the antioxidant compound alpha-lipoic acid in lowering triglycerides. High triglyceride levels often occur in obesity, and are a predictor of atherosclerosis, nonalcoholic fatty liver disease, and even premature mortality. Proper diet, exercise, and weight loss can help reduce triglycerides, but are not effective for everyone.
For the current research, Regis Moreau and colleagues at Oregon State University's Linus Pauling Institute used rats bred to become obese and diabetic. At five weeks of age, the animals were given 200 milligrams per kilogram body weight R-alpha-lipoic acid per day. Control rats were matched for food intake with the animals that received lipoic acid during the five week treatment period.
Not unexpectedly, triglyceride levels following meals were higher by the end of the study compared to pretreatment levels. However, while triglyceride levels doubled among those that received alpha-lipoic acid, they increased by over 400 percent in the control group.
Alpha-lipoic acid's mechanisms include inhibition of specific gene expression in the liver, lowering liver triglyceride secretion, and stimulating the clearance of triglyceride-rich lipoproteins. When the animals' livers were examined at the study's conclusion, those from rats treated with lipoic acid showed elevated glycogen levels, which suggests that more consumed carbohydrates were being stored as glycogen rather than becoming triglycerides.
According to the authors, the study is the first to identify the lipoic acid's molecular targets in lowering triglycerides, and to show its effect on liver enzymes that control triglyceride production. Although the benefit of lipoic acid on triglyceride levels was comparable to that of currently used drugs, the mode of action was determined to differ from fibrates. Importantly, supplementation with alpha-lipoic acid has not been associated with the side effects and safety concerns of pharmaceuticals used to treat hypertriglyceridemia.
"Lipoic acid is known to influence glucose uptake, and bring down blood glucose by increasing its transport into skeletal muscle," stated Dr Moreau, who is an assistant professor at the Linus Pauling Institute. "Less has been done to study its potential value in reducing triglycerides."
"The extent of triglyceride reduction was really dramatic, we didn't expect it to be this profound," he remarked. "The potential is good that this could become another way to lower blood triglycerides and help reduce the risk of atherosclerosis. It's pretty exciting."
"We believe that a novel means of controlling triglyceridemia in this animal model has been revealed," the authors write. "Given its strong safety record, lipoic acid may have therapeutic applications for the treatment or prevention of hypertriglyceridemia and diabetic dyslipidemia in humans."
The cause and progression of atherosclerosis are intimately related to the health of the inner arterial wall. Arteries are composed of three layers. The outer layer is mostly connective tissue and provides structure to the layers beneath. The middle layer is smooth muscle; it contracts and dilates to control blood flow and maintain blood pressure. The inner lining consists of a thin layer of endothelial cells (the endothelium) that provides a smooth, protective surface. Endothelial cells prevent toxic, blood-borne substances from penetrating the smooth muscle of the artery. They also respond to changes in blood pressure and release substances into the cells of the smooth muscle that help change the muscle tone of the artery. Furthermore, endothelial cells secrete chemicals that provoke a protective response in the artery after an injury. This protective response includes signaling smooth muscle cells and white blood cells to congregate at the site of an injury.
As we age, however, the endothelium becomes leaky, allowing lipids and toxins to penetrate the endothelial layer and enter the smooth muscle cells. As a result, smooth muscle cells gather at the site of the injury, and the artery loses some flexibility. In response, the endothelium signals white blood cells to congregate along the cell wall. These white blood cells produce pro-inflammatory substances, such as leukotrienes and prostaglandins, as well as damaging free radicals that attack the endothelium (Touyz RM 2005). Toxins soon begin to penetrate into the arterial wall, where lipids such as LDL, cholesterol, and triglycerides accumulate and become oxidized.
At this point, the atherosclerotic process has begun in earnest. In response to the oxidized lipids, the body mounts an intensive immune response that causes more white blood cells to attack the fats, producing more inflammation within the arterial wall. In an attempt to heal the injury, smooth muscle cells begin to produce collagen to form a cap over the injury site. The mixture of oxidized lipids, white blood cells, and smooth muscle cells forms a plaque deposit. Over time, calcium accumulates on the deposit and forms a brittle cap. If this calcified plaque ruptures, a blood clot can form, and the clot may result in a heart attack or stroke.
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A significant number of studies underscore the health benefits of supplementing with creatine, a nitrogenous organic acid (amino acid derivative) that is synthesized by the body, mainly in the liver. In fact, recent clinical trials demonstrated creatine as having positive effects on strength and body composition and improving muscular performance in older adults, especially when combined with a resistance training exercise protocol. Fourteen weeks of resistance exercise training resulted in significant increases in all measurements of strength and functional tasks and muscle fiber area for both creatine and placebo groups. However, the group getting the creatine resulted in significantly greater increases in fat-free mass, greater increase in isometric knee extension, greater gains in isometric dorsiflexion strength, as well as a significant increase in intramuscular creatine levels.