Alpha-Lipoic Acids - Benefits and Risks

Introduction

Alpha-lipoic acid, also known as thioctic acid, is derived from caprylic acid. As an antioxidant, it is known as acetate replacing factor, ALA, lipoic, etc. It has a dithiol functional group that removes reactive oxygen species, called ROS, by the reduction of other antioxidants. These reactive oxygen species, like superoxide radicals, hydroxyl radicals, and singlet oxygen, are neutralized by dihydrolipoic acid. In this way, it is favorable in oxidative-stress-associated conditions like ischemic reperfusion or radiation injury.

The alpha-lipoic acid also acts as an iron-chelating agent due to the presence of thiol groups (organosulfur compounds) in it. It also proves to be effective in diabetic neuropathy (a type of nerve damage that affects legs and feet) conditions as it improves microcirculation in such patients by increasing nitric-oxide-mediated vasodilation (dilatation of blood vessels leads to the increased blood supply and reduction in blood pressure induced by nitric oxide).

What Is the Mechanism of Action of Alpha-Lipoic Acid?

The presence of a dithiolane ring in the alpha-lipoic acid is responsible for its chemical reactivity. The two forms of alpha-lipoic acid-oxidized lipoic acid (LA) and reduced dihydrolipoic acid (DHLA) can forage reactive oxygen species without getting complicated. It revives many other antioxidant factors, such as vitamin C and vitamin E, and also enhances the synthesis of glutathione.

The anti-inflammatory effect of alpha-lipoic acid occurs due to the inhibition of kappa B kinase that suppresses the activation of factor NF-kB. Therefore, there is a stopping of the action of other cytokines responsible for the inflammation.

How Do Alpha-Lipoic Acids Get Administer?

Alpha-lipoic acids can be administered in the following two ways :

• Oral Route - As per the studies, a daily dose of 300 mg of alpha-lipoic acid supplements for three months helps to improve diabetic retinopathy.

• Intravenous Injection - A daily administration of 600 mg of alpha-lipoic acid improves neuropathic symptoms.

What Are the Benefits of Alpha-Lipoic Acid?

Alpha-lipoic acid, as a food additive, is beneficial in treating and managing several diseases like cardiovascular disease, cancer, and neurological disorders. It also possesses anti-inflammatory, anti-aging, cognitive, and detoxifying properties. The following are the benefits of alpha-lipoic acids:

1. Anti-diabetic Agent - Diabetes mellitus is one of the most common and severe worldwide problems. It occurs due to the disturbed metabolism of carbohydrates, proteins, and lipids. It is responsible for the evolution of many severe ailments like atherosclerosis, hypertension, heart failure, myocardial infarction, neuropathic pain, and stroke. Studies claim that the production of excessive reactive oxygen species declines the antioxidant capacity resulting in diabetes mellitus. Alpha-lipoic acid can enhance sugar uptake in insulin-sensitive and insulin-resistant muscle tissue.

2. Improves Alzheimer's Disease - This neurological disease is associated with cognitive impairment and functional and behavioral problems. In these patients, memory loss occurred due to the accumulation of beta-amyloid and increased tau. To treat Alzheimer's disease and other neurological disorders, non-steroidal anti-inflammatory drugs (NSAIDs) have been used. Still, these drugs cannot be used for a more extended period as they cause gastrointestinal toxicity. This toxic effect results from the inhibition of cyclooxygenase (COX) - a rate-limiting enzyme used as a precursor for the production of prostaglandins and thromboxane. Therefore alpha-lipoic acids are used to treat neurological disorders like Alzheimer's disease. These alpha-lipoic acids increase the formation of acetylcholine by the activation of choline acetyltransferase. It leads to an increase in the absorption of glucose and improved production of acetylcholine.

3. Suppresses Cancer Growth - Alpha-lipoic acid plays a vital role in cancer therapy. The Warburg effect, also known as aerobic glycolysis, is an event in which the glucose gets converted to lactate by the cancer cells to produce adenosine triphosphate (ATP). In cancer cells, if the process of aerobic glycolysis continues, there will be activation of oncogenes leading to the loss of the tumor suppressor genes. Hence, the phenomenon results in the progression of cancer. To create the anticancer effect, there must be inhibition of this Warburg effect or aerobic cycle. Alpha-lipoic acid has shown delayed growth of tumors in breast cancer by inhibiting cell proliferation, forming lactate, and increasing apoptosis in neuroblastoma cell lines.

4. Weight Control - Obesity occurs due to abnormal fat storage, resulting in severe pathological diseases. It can be controlled by using interventional therapies along with an increased intake of nutrient supplements. Studies have shown that alpha-lipoic acid plays a vital role in weight control, and a reduction in body weight and waist circumference has been observed.

5. As a Biomarker in Multiple Sclerosis - Surveys have been conducted to check the effect of alpha-lipoic acid in patients with multiple sclerosis. It is observed that 1200 mg/day administration of alpha-lipoic acid leads to a considerable- reduction in serum levels of IL-4, ICSM-1 TGF, and a significant improvement in the patients' walking.

6. Prevention of Threatened Miscarriage - During the first trimester of pregnancy, there are chances of threatened miscarriage that can cause abnormalities like intrauterine bleeding and sub-chronic hematoma. Clinical trials have been conducted to study the role of alpha-lipoic acid and progesterone therapy in preventing irregularities in pregnancy.

What Are the Risks Associated With Alpha-Lipoic Acid?

Alpha-lipoic acid has no side effects, so it is considered a safe supplement. A daily dose of 200 - 2400 mg/day does not harm. But sometimes allergic reactions like hives, dyspnea, and swelling on lips, face, tongue, or throat occur. One should stop taking alpha-lipoic acid if the following symptoms are seen:

• Hypoglycemia.

• Headache.

• Confusion.

• Irritability.

• Dizziness.

• Fading.

• Tachycardia.

• Sweating.

• Nausea.

• Skin rash.

Alpha-lipoic acid should also be avoided during pregnancy or breastfeeding, but no firm evidence of harm to an unborn baby is proven.

Interactions With Other Drugs- Major exchanges are seen with the following drugs:

1. Amlodipine.

2. Aspirin.

3. Biotin.

4. Folic Acid.

5. Lisinopril.

6. Gabapentin.

7. Atorvastatin.

Conclusion

Alpha-lipoic acid is an antioxidant and shows various benefits, as mentioned in the article. But as per some studies, the therapeutic consumption of alpha-lipoic acid is limited because of its short half-life and bioavailability, which leads to the degradation of hepatocytes, and decreased solubility in the stomach. Several formulations are used to increase the bioavailability, like amphiphilic matrices. This helps to increase the solubility and absorption of alpha-lipoic acid in the intestine. Many other uses of alpha-lipoic acid treat disorders of the central nervous system like schizophrenia, Alzheimer's disease, and multiple sclerosis.