Pharmacology: Alpha Lipoic Acid also known as Lipoic acid or Thioctic acid, is an antioxidant - a substance that prevents cell damage caused by compounds called free radicals in a process called oxidative stress. High level of blood glucose is one cause of oxidative stress. Intravenous and oral Alpha Lipoic Acid are used for the treatment of diabetic neuropathy.
More than 20% of diabetic patients develop peripheral neuropathy, a type of nerve damage that may result in pain, loss of sensation and weakness, particularly in the lower extremities. In addition to the pain and disability caused by diabetic neuropathy, it is a leading cause of lower limb amputation in diabetic patients. A meta-analysis that combined the results of four randomized controlled trials, found that treatment with 600 mg/day of intravenous racemic Lipoic acid for 3 weeks significantly reduced the symptoms of diabetic neuropathy to a clinically meaningful degree.
Alpha Lipoic Acid: Reduces Neuropathy symptoms like pain, paresthesia and numbness. Alpha Lipoic Acid is a powerful natural antioxidant. It has been used to improve diabetic neuropathies and has reduced pain in several studies. Supplementing with Alpha Lipoic Acid for six months has been found to reverse the cause of diabetic nerve damage and improve this painful condition. Chromium supplementation enhances the sensitivity of insulin receptors in the body. Zinc plays important roles in growth and development, the immune response, neurological function and reproduction. Numerous aspects of cellular metabolism are zinc-dependent.
Alpha Lipoic Acid - Mitochondrial Anti Oxidant: Alpha-lipoic acid (also known as thioctic acid) was discovered in 1951 as a molecule that assists in acyl-group transfer and as a coenzyme in the Krebs cycle. Alpha-lipoic acid is a powerful Mitochondrial antioxidant. Several qualities distinguish alpha-lipoic acid from other antioxidants: Alpha Lipoic Acid can be synthesized by animals and humans; it neutralizes free radicals in both the fatty and watery regions of cells & Alpha Lipoic Acid functions as an antioxidant in both its reduced and oxidized forms.
Alpha Lipoic Acid in its reduced form (DHLA) is capable of directly regenerating ascorbic acid from dehydroascorbic acid and indirectly regenerating vitamin E. Researchers have also found Alpha Lipoic Acid increases intracellular glutathione and coenzyme Q10 levels. Alpha-lipoic acid appears capable of chelating certain metals. It forms stable complexes with copper, manganese and zinc.
Mechanisms that may account for lipoic acid's benefit in preventing diabetic complications include prevention of protein glycosylation and inhibition of the enzyme aldose reductase, the latter of which subsequently inhibits conversion of glucose and galactose to sorbitol.
Chromium also called Glucose Tolerance Factor (GTF), is a nutrient that plays a vital role in enhancing the action of insulin produced in the body. Biologically active form of chromium participates in glucose metabolism by enhancing the effects of insulin. Because chromium appears to enhance the action of insulin and chromium deficiency has resulted in impaired glucose tolerance, chromium insufficiency has been hypothesized to be contributing factor to the development of Type 2. It is thought to improve blood sugar status in diabetic patients by functioning as a co-factor for insulin.
Chromium is an essential trace mineral required by the human body for normal carbohydrate and lipid metabolism. Nutritional chromium, is found in foods and supplements. Chromium potentiates the biological actions of insulin, a hormone that is critical for the normal regulation of carbohydrate, lipid and protein metabolism. Evidence of chromium's role was first suggested in 1957 when a "glucose tolerance factor" (GTF), found in brewer's yeast, prevented an age-related decline of glucose tolerance in rats. Chromium III was later identified as the active ingredient of "glucose tolerance factor" (GTF).
Zinc is an essential mineral to the body, plays the important roles in growth and development, the immune response, neurological function. Nearly 100 different enzymes depend on zinc for their ability to catalyze vital chemical reactions.
Moderate zinc deficiency may be relatively common in individuals with diabetes mellitus. Increased urinary zinc excretion appears to contribute to the marginal zinc nutritional status that has been observed in diabetics. More recently, supplementation of type 2 diabetics with 30 mg/day of zinc for 6 months reduced a non-specific measure of oxidative stress (plasma TBARS). Studies indicate that Zinc supports a healthy immune system as well as improves glucose homeostasis. Zinc also exerts anti-oxidant effect especially on patients with diabetes who are subject to deleterious oxidative stress.
Zinc is an essential mineral of "exceptional biologic and public health importance". Zinc deficiency is associated with many diseases. As a Dietary supplement, Zinc possess antioxidant properties & also beneficial to the body's immune system. Indeed, Zinc deficiency may have effects on virtually all parts of the human immune system. Zinc helps stimulate the action of more than 100 enzymes. Zinc also helps to speed up the healing process after an injury.
Pharmacodynamics: Mechanism of Action: Alpha Lipoic Acid inhibits the nerve damage caused by free radicals due to increased oxidative stress. Alpha Lipoic Acid improves nerve blood flow and increases sensory conduction. Chromium; it has been found to activate Insulin Receptor Kinase activity up to 7 fold. This activation may lead to increased insulin sensitivity, increases number of Insulin receptors and facilitates the attachment of Insulin of these sites. Zinc, nearly 100 different enzymes depend on zinc for their ability to catalyze vital chemical reactions.
Mechanism of Action & Health Benefits: Antioxidant Activities: Scavenging Reactive Oxygen and Nitrogen Species: Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are highly reactive compounds with the potential to damage DNA, proteins, and lipids (fats) in cell membranes. Both LA and DHLA can directly scavenge (neutralize) physiologically relevant ROS and RNS.
Regeneration of Other Antioxidants: When an antioxidant scavenges a free radical, it becomes oxidized itself and is not able to scavenge additional ROS or RNS until it has been reduced. DHLA is a potent reducing agent with the capacity to reduce the oxidized forms of several important antioxidants, including vitamin C and glutathione.
Enhancing immunity & Insulin sensitivity: Zinc helps in improving the immune system and Chromium Picolinate helps improving the Insulin Sensitivity of cells & act as Glucose Tolerance Factor.
Helps to influence glucose control, and prevent chronic hyperglycemia-associated complications such as neuropathy, retinopathy & nephropathy. Alpha Lipoic Acid is also widely tested Chronic liver complications & age related decline in cognitive function.
As a powerful anti oxidant, it can be used for patients of metabolic syndrome to reduce long term cardiovascular & neurological complications due to oxidative stress like Myocardial infarction, atherosclerosis and Stroke.
Pharmacokinetics: Alpha Lipoic Acid appears to be readily absorbed from an oral dose and converts easily to its reduced form, dihydrolipoic acid (DHLA), in many tissues of the body. The effects of Alpha Lipoic Acid and DHLA are present both intra- and extracellularly. There may also be differences in bioavailability of the two isomers of LA. After oral dosing with LA, peak plasma concentrations of R-LA were found to be 40%-50% higher than S-LA, suggesting that R-LA is better absorbed than S-LA (12, 14, 16). Following oral administration, both isomers are rapidly metabolized and excreted.