The Potent Antioxidant Alpha Lipoic Acid

    

    

    Figure 1:  The chemical structure of Alpha lipoic and Dihydrolipoic acid.
    
    

Antioxidant activity

DHLA, the reduced form of ALA, is capable of exerting an antioxidant effect directly by donating electrons to a pro-oxidant or an oxidized molecule. It can regenerate ascorbic acid from dehydroascorbic acid, and it can indirectly regenerate vitamin E back from its oxidized state [6]. As well, ALA metabolites have been shown to have antioxidant effects [7].

ALA, the oxidized form of DHLA, can exert an antioxidant effect. But this does not mean there is any donation of electrons by ALA to a pro-oxidant or oxidized molecule, since there are none to give. However, it has been documented that ALA can inactivate free radicals, which is a significant antioxidant effect [8]. Also, the ability of ALA to chelate metals can produce an antioxidant effect [9]. DHLA can exert a pro-oxidant effect of donating its electrons for the reduction of iron, which can then break down peroxide to the prooxidant hydroxyl radical via the Fenton reaction [10]. So, ALA and its reduced form DHLA, can promote antioxidant properties. ALA has been effectively chelate toxic metals directly, and it also indirectly strongly supports the chelation of metals by its ability to increase glutathione levels inside the cells. Glutathione and its associated enzymes play important roles in the ability of the body to chelate and excrete a wide variety of toxins, toxic metals included. Metals known to form complexes directly with ALA and DHLA include manganese, zinc, cadmium, lead, cobalt, nickel, iron, copper, cadmium, arsenic, and mercury.

Free radicals, once formed, are capable of disrupting metabolic activity and cell structure. When this occurs, additional free radicals are produced which, in turn, can result in more extensive damage to cells and tissues. The uncontrolled production of free radicals is thought to be a major contributing factor to many degenerative diseases. Alpha-lipoic acid is unique among biological antioxidants, because it is soluble in both water and lipids. This allows it to neutralize free radicals just about everywhere in the body, inside and outside the cells. Due to its unique sulfur-containing structure, alpha-lipoic acid can scavenge several types of free radicals, such as the highly reactive hydroxyl, and singlet oxygen free radicals. It is also capable of suppressing the generation of free radicals in the first place, since alpha-lipoic acid chelates transition metals, such as iron and copper. Alpha-lipoic acid is involved in many different antioxidant functions in virtually all body tissues, So, it has been called the universal antioxidant [11].

Diabetes mellitus represents a serious global health problem. It is a common disease that’s affecting many millions of people all over the world. DM is one of the main effects are the decrease in β-cell mass, which is ubiquitous in most of all patients with type 1 diabetes [12]. Alpha lipoic acid showed a potential role in managing diabetes and improving dyslipidemia and so, it can reduce cardiovascular complications which resulted due to diabetes mellitus. Alpha lipoic acid is able to increase cellular uptake of glucose by recruiting glucose transporter-4 into cell membrane [13]. Alpha lipoic acid has the ability to decrease oxidative stress, which produced by diabetes mellitus by increasing the sensitivity of insulin, thereby maintain glycemic control decrease reactive oxygen species generated by hyperglycemia and dyslipidaemia [14]. In addition, ALA significantly improved deterioration of vitamin C and attenuates the status of antioxidant enzymes and biomarkers of oxidative stress, which arises by diabetes mellitus [14].

α-Lipoic Acid and Obesity

Obesity is an important public health disease that predisposes people to many diseases such diabetes, coronary heart disease, stroke, obstructive-sleep apnea and certain forms of cancer [15].

α-lipoic acid supplementation at a dose of 300 mg/day might help to could help to promote weight loss and fat mass reduction in healthy overweight/obese women following an energy-restricted balanced diet [16]. Moreover, Koh [17] stated that supplementation of α-lipoic acid at a dose of 1200-1800 mg/day together with a low calorie diet, overweight and obese subjects promotes weight loss as well as Body Mass Index (BMI) and waist circumference reduction, but this effect showed only significant at the highest dose.

Carbonelli [18] reported that α-lipoic acid (800 mg/day) promotes the reduction of weight, fat mass and waist circumference in overweight and obese subjects, but not in normal weight subjects, suggesting that these effects could be due to the increased satiety induced by α-lipoic acid. α-lipoic acid could promote weight loss by reducing food intake and stimulating energy expenditure [19].

α-Lipoic Acid and Peptic Ulcer

Peptic ulcer is a gastrointestinal defect, which result due to imbalance between protective and effective agents and it is also due to H. Pylori infection. There are several factors as smoking, alcohol, some types of drugs such as aspirin can implicate in ulcer formation [20].

Hcl secretion which can be stimulated by acetylcholine, histamine and stress. Some drugs like Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) cause an inhibition of the bicarbonate production and hence cause the formation of ulcers [21].

Alpha lipoic acid protected the gastric mucosa which covers the stomach wall from damage via lowering volume secretion, increment the pH level and mucous secretion [22]. Moreover, Hussein [23] reported that using alpha lipoic acid as a pretreatment of gastric ulcer resulted in an effective protection against ulcer and oxidative damage in gastric mucosa tissue, which induced by ethanol in rats, α-lipoic acid was able to mend serum biochemical parameters such as Nitric Oxide (NO) and Sialic acid, also, GPX, SOD and CAT enzyme as an antioxidant enzymes and non-enzymatic antioxidant as reduced Glutathione (GSH) defense system.

α-Lipoic Acid and Alzheimer’s Disease

Alzheimer’s Disease (AD) is a neurological disorder that characterized by profound memory loss and progressive dementia. Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) have been suggested for the potential treatment of neurodegenerative diseases, such as Alzheimer’s Disease (AD). Prolonged use of NSAIDs, however, produces Gastrointestinal (GI) toxicity. The selection of the antioxidant, ALA was based on the proposed role of oxidative stress in the development and/or progression of AD [24]. Alpha lipoic acid has the ability to decrease cognitive impairment and may be a successful therapy for Alzheimer’s disease and any disease related dementias. Mitochondria lost its efficiency with age due to the oxidation of proteins, lipids, DNA, and RNA [25].

Alpha lipoic acid increases the production of Acetylcholine (Ach) via activating choline acetyl transferase and increases glucose uptake, hence, supplying more acetyl-CoA for the production of Ach of each. Alpha lipoic acid can chelates redox-active transition metals, hence inhibiting the formation of hydroxyl radicals and also scavenges reactive oxygen species, thereby increasing the concentration levels of reduced Glutathione (GSH). Also, a decrease of inflammatory marker is also achieved by the same mechanism. Alpha lipoic acid can scavenge lipid peroxidation products as hydroxynonenal and acrolein. Dihydrolipoic acid, is the active compound which is responsible for the most of these beneficial effects [26,27] (Figure 2).

    

    

    Figure 2:  The mechanism action of alpha lipoic acid in controlling Alzheimer’s disease.