ALPHA LIPOIC ACID: FUNCTION, PROPERTIES, BENEFITS, CONTRAINDICATIONS - BIOLOGY - 2024

The alpha lipoic acid (LA or ALA, of the English α-lipoic acid),-dithiolane-3-pentanoic 1.2 or simply thioctic acid, is a natural compound found in the mitochondria of animal and plant cells which has many functions relevant from a metabolic point of view.

It was first isolated in 1950 from bovine liver. It contains two thiol groups (SH) that can participate in oxidation and reduction reactions, which is why it is considered an excellent natural antioxidant agent.

Chemical structure of alpha lipoic acid (Source: Yikrazuul via Wikimedia Commons)

This organic acid acts as a coenzyme for some proteins with enzymatic activity involved in the metabolism of proteins, carbohydrates and fats. In addition, it also acts as a free radical scavenger, hence the term "antioxidant".

In view of its easy absorption, transport and assimilation, lipoic acid is widely used as a dietary supplement, in the formulation of lotions and as an active compound in some drugs designed for patients with heart conditions, diabetes, obesity, etc.

Biological function

Alpha lipoic acid, thanks to its structural characteristics and similar to glutathione, another sulfurized antioxidant, is part of a redox couple, as it can be oxidized or reduced, depending on the needs of the cell.

However, unlike glutathione, its reduced pair, dihydrolipoic acid or DHLA (dihydrolipoic acid), also has antioxidant properties, a fact demonstrated by its ability to actively participate in redox reactions.

Alpha lipoic acid-dihydrolipoic acid redox pair (Source: Yikrazuul via Wikimedia Commons)

The main function of this acid has to do with its action as a cofactor in two highly relevant mitochondrial enzyme complexes: the pyruvate dehydrogenase complex and the α-ketoglutarate dehydrogenase complex.

It is also part of the enzymatic complex of branched chain ketoacid dehydrogenase or BCKADH (Branched-chain keto-acid dehydrogenase), so it participates in obtaining energy from amino acids such as leucine, valine and isoleucine.

Immediately after its synthesis, which occurs inside the mitochondria, lipoic acid is covalently linked with these complexes, where it performs its functions.

Some authors consider that this compound participates in the prevention of some cellular damages, as well as in the restoration of the levels of vitamin E and vitamin C. Since it is capable of chelating different transition metals such as iron and copper, this acid blocks the production of oxygen free radicals.

It works to improve neuronal conduction and its association with mitochondrial enzymes results in a better metabolic use of carbohydrates consumed in the diet.

Although it has been studied in less depth, lipoic acid has an additional role in the fate of blood glucose and its transport from circulating blood to cells. This compound is thought to exert this function directly on the cell membrane, but this has not been fully elucidated.

It facilitates the repair of oxidized proteins, especially those rich in cysteine ​​and methionine residues, which are amino acids that have sulfur atoms in their structure.

Synthesis

Alpha lipoic acid (6,8-dithio-octanoic acid) is an organic acid with 8 carbon atoms that has two sulfur groups and a single chiral center. The thiol groups are located between carbon atoms 6 and 8 and are attached to each other through a disulfide bridge bond.

It has, in its structure, an asymmetric carbon atom, so it is possible to find two optical isomers in nature: R-alpha lipoic acid and L-alpha lipoic acid.

This compound (in the form of R-alpha lipoic acid) is endogenously synthesized in the mitochondria, which are eukaryotic cytosolic organelles (present in both plants and animals) responsible for part of energy production and cellular respiration. It is also easily assimilated from the diet.

The enzymatic synthesis of alpha lipoic acid occurs from octanoic acid and cysteine ​​residues (which function as a source of sulfur, that is, from thiol groups), after which it is joined to the protein complexes for which it works. as an enzymatic cofactor.

The R-alpha lipoic acid isoform is the only one of the two existing isoforms that has biological activity and this is thanks to the fact that it can be conjugated to proteins through amide bonds with conserved lysine residues, forming a lipoamide.

Properties and health benefits

Alpha lipoic acid is a fat-soluble sulfur coenzyme (it is also soluble in water) with important functions in the metabolism of lipids, carbohydrates and proteins at the cellular level. In other words, it is a coenzyme involved in the production of energy in the form of ATP from these substrates.

Thanks to its solubility characteristics (it is soluble both in water and in lipid or fatty compounds), this acid can exert its functions as an antioxidant agent in almost all parts of cells and organisms.

The presence of two sulfur atoms in its structure allows it to neutralize free oxygen radicals such as hydroxyl, highly reactive groups, and solitary oxygen radical atoms.

Given that it is efficiently absorbed and transported to tissues and cells, lipoic acid is taken as a dietary supplement by those who seek to complement their antioxidant defense system and maintain an adequate glucose metabolism.

Medical utilities

There is increasing scientific evidence regarding the therapeutic potential of lipoic acid for man. This has been exploited from a clinical point of view for the treatment of diabetes Mellitus, especially to reduce the nervous symptoms related to this disease such as pain, numbness of upper and lower limbs and a burning sensation.

Its oral or intravenous intake has been shown to be useful in lowering blood glucose (glycemic) levels in patients with type II diabetes, but not in patients with type I diabetes.

It has been used successfully for the treatment of interstitial cystitis (painful bladder syndrome), which is typical in women and causes severe discomfort in the pelvic area; as well as in some diseases characterized by neurological damage.

Since it increases tissue levels of glutathione, lipoic acid is also recommended for patients suffering from arterial hypertension (as a hypotensive), since glutathione prevents the deleterious modification of calcium channels.

It has also been used as an anti-inflammatory agent and as a protector of the vascular system.

Aesthetic utilities

Some pharmaceutical companies include lipoic acid in the formulation of vitamins such as the B complex, but this is not considered a vitamin per se.

Likewise, some "anti-aging" and "anti-wrinkle" body lotions include around 5% lipoic acid, as its antioxidant effects seem to help reduce fine lines and the dryness and robustness inflicted on the skin by sun exposure.

Fine lines (Image by Kelsey Vere on pixabay.com)

Additionally, its ingestion or topical application improves the elastic properties of the skin, reducing the amount of wrinkles or preventing their appearance.

Some research suggests that prolonged consumption of lipoic acid (more than 20 weeks) can contribute to weight loss in people with high rates of obesity.

Foods rich in alpha lipoic acid

Since it is synthesized in both plants and animals, this powerful natural antioxidant is found in many foods that we consume daily. It is found in preparations rich in yeast extracts, in animal viscera such as liver and kidney, and in plants such as spinach, broccoli and potatoes.

It is also found in Brussels sprouts, beets and carrots, rice, and red meats, especially "muscle meats" such as heart.

Contraindications

There are no important contraindications for the intake of lipoic acid by adults, but you should consult your family doctor if you want to consume, as it may have interactions with some medications, especially with antibiotics, anti-inflammatories, tranquilizers, vasodilators, etc.

When lipoic acid is taken by mouth, some people may get a rash. In the case of its topical application as a lotion on the skin, there does not seem to be any side effect, at least up to 12 weeks of continuous use.

Giving lipoic acid intravenously is quite safe. Pregnant women can consume up to 600 mg of this acid daily for more than 4 weeks without observing any side effects.

The most severe contraindications have been observed in children between 1 and 3 years of age, for whom the administration of large amounts of this acid is not recommended as it can cause seizures, vomiting and loss of consciousness.

Its use is not recommended for alcoholics, as alcohol consumption decreases the amount of vitamin B1 in the body, which can cause serious implications if mixed with lipoic acid.

Experimental data

Some studies done in animals suggest that consuming lipoic acid can be risky, but it depends a lot on the species.

Thus, studies carried out in canines report a fairly high tolerance, which is not true for rodents, in which numbness, apathy, piloerection and involuntary closure of the eyelids have been reported after the administration of more than 2,000 mg of acid lipoic.

References

1. Alpha-Lipoic Acid: The Universal Antioxidant with Metabolic Functions. (2003). Douglas Laboratories, 1–2.
2. Durand, M., & Mach, N. (2013). Alpha lipoic acid and its antioxidant against cancer and diseases of central sensitization. Nutricion Hospitalaria, 28 (4), 1031–1038.
3. Golbidi, S., Badran, M., & Laher, I. (2011). Diabetes and alpha lipoic acid. Frontiers in Pharmacology, 2 (69), 1–15.
4. Shay, KP, Moreau, RF, Smith, EJ, Smith, AR, & Hagen, TM (2009). Alpha-lipoic acid as a dietary supplement: Molecular mechanisms and therapeutic potential. Biochimica et Biophysica Acta - General Subjects, 1790 (10), 1149–1160.
5. Singh, U., & Jialal, I. (2008). Alpha-lipoic acid supplementation and diabetes. Nutrition Reviews, 66 (11), 646–657.