Alpha lipoic acid for anxiety

 

About

Alternative name: α-lipoic acid, alpha-lipoic acid (ALA), thioctic acid, DL-alpha-Lipoic acid

Chemical formula: C8H14O2S2

Active ingredient: α-lipoic acid

Source: Foods in which it is bound to lysine in proteins,[1]Such as spinach, cauliflower, tomatoes and organ meats [2][3]

Legal status: ALA is a generally safe supplement that can be purchased over the counter[4]

What is Alpha lipoic acid

Alpha lipoic acid is an enzyme present in mitochondria that, much like vitamins, aids in the conversion of nutrients into energy through enzymes. It also helps in the elimination of free radicals, which accelerate aging and disease.[5]Alpha lipoic acid is taken in by cells via the intestine and possesses qualities of both fat and water solubility. This dual solubility enables it to traverse the entire body and access any cell site, exerting a comprehensive effect on the human body. It acts as a versatile antioxidant, being soluble in both fat and water. Moreover, alpha-lipoic acid prolongs the biochemical lifespan of vitamins C and E, as well as other antioxidants, allowing them to continue functioning as antioxidants.

Dr.Irwin C. Gunsalus in the early 1950s, for essential growth factors in the digestive system bacterium Enterococcus, discovered chemical forms of alpha lipoic acid.[6]

In 1979, Dr. Burton made the initial clinical use of lipoic acid and published in the New England Journal of Medicine that Alpha lipoic acid can be used to treat acute liver failure resulting from poisonous mushrooms.。[7]

In the 1980s, alpha lipoic acid began to be discovered as a powerful antioxidant with both fat-soluble and water-soluble characteristics. It has the effect of fighting various chronic diseases, so it gradually attracted attention.

The Best Food Sources for Alpha Lipoic Acid

Chart from Superfoodly


1. Alpha lipoic acid can act as a neuroprotective agent due to its powerful antioxidant properties. It promotes neuronal regeneration in rats[29] and prevents neuronal degeneration in cells.[30]
In rats, alpha lipoic acid administered immediately after stroke restored damaged neurons and promoted long-term functional recovery through enhanced anti-inflammatory and antioxidant effects.

Another study in rats showed that lipoic acid can reduce brain damage and improve survival after stroke. In cell studies, ALA exposure increased glutathione (GSH), which in theory could help improve brain function , but this effect has not been studied in animals or humans [31].
2, Studies have shown that lipoic acid increases the levels of acetylcholine (Ach) and choline acetyltransferase in the brain, and decreases the activity of acetylcholinesterase (AchE). Acetylcholine is a common neurotransmitter in the central and peripheral nervous systems and is primarily involved in memory and overall function in the brain.[32]

Lipoic acid antioxidant may reduce brain damage
Increase acetylcholine in the brain
Can protect the blood-brain barrier
Neutralizes toxic metals and protects the nervous system
According to clinical evidence, lipoic acid overall does not help much with depression, but it does help with overall physical health. It can indirectly improve mental health by improving metabolic chronic diseases in the human body.

Alpha lipoic acid is found in a wide variety of foods from plant and animal sources, but dietary sources contain very low amounts of alpha lipoic acid. For example, purifying alpha lipoic acid to determine its structure used an estimated 10 tons of liver residue, yielding 30 milligrams of alpha lipoic acid. [8]

Among plant-source foods, spinach contains the highest amount of alpha lipoic acid, followed by broccoli and tomatoes; in animals, visceral tissues have the highest alpha lipoic acid content, and meat has very little. [9]

Therefore, all alpha lipoic acid available as supplements is chemically synthesized.

Unlike alpha lipoic acid in food, alpha lipoic acid in supplements is not bound to protein. [10] Additionally, the amount of alpha lipoic acid in dietary supplements (50-600 mg) may be 1,000 times higher than the amount obtained from the diet。

If you plan to supplement alpha lipoic acid to health-improving doses, food sources will be difficult to achieve and you will need to add dietary supplements.

The health benefits of Alpha lipoic acid

Alpha lipoic acid(ALA), is a naturally occurring compound that plays essential roles in cellular metabolism. It is considered a coenzyme because it is involved in various enzymatic reactions in the body, particularly in the mitochondria, which are the energy-producing organelles within cells. Here are some key aspects of lipoic acid:

Antioxidant: Lipoic acid is a potent antioxidant,[11] which means it can neutralize harmful free radicals in the body. This antioxidant property helps protect cells and tissues from oxidative damage, [12]which is associated with aging and various diseases.

Energy Production: Lipoic acid is a cofactor for several enzymes involved in energy metabolism, including the citric acid cycle (Krebs cycle) and the production of adenosine triphosphate (ATP), the cell's primary energy currency. It helps convert glucose into energy.[13][14]

Regeneration of Other Antioxidants: Lipoic acid can regenerate other important antioxidants like vitamin C and vitamin E, enhancing their effectiveness in combating oxidative stress.[15][16][17][18]

Blood Sugar Control: Some research suggests that lipoic acid may improve insulin sensitivity and help regulate blood sugar levels. [19]It is sometimes used as a dietary supplement for individuals with type 2 diabetes.[20]

Neuroprotection: Lipoic acid has shown promise in protecting nerve cells and may be used in the management of conditions like diabetic neuropathy.[21][22][23][24]

Chelation: Lipoic acid has chelating properties, meaning it can bind to certain heavy metals and toxins in the body, potentially aiding in their removal.[25][26][27][28]

Health benefit of taking lipoic acid for brain and nerves

Because alpha-lipoic acid can easily enter the brain and has a strong ability to neutralize the damaging effects of oxidative stress, it has become the subject of in-depth research on preventing free radical damage to the nervous system and helping to protect the brain and nervous tissue.

3，Another study in rats showed that lipoic acid can reduce brain damage and improve survival after stroke. In cell studies, ALA exposure increased glutathione (GSH), which in theory could help improve brain function , but this effect has not been studied in animals or humans [31].

4，Lipoic acid can chelate (bind) toxic metals and neutralize them, which can protect the nervous system.

Lipoic acid reduces methylmercury-induced brain damage in rats [34]

Research about Alpha Lipoic Acid for mental health

A research review conducted in 2018 [35] encompassed 34 animal trials, field studies, and other research on the impact of lipoic acid on mental health. The findings indicated that lipoic acid exhibits a noticeable influence on a range of mental health conditions and can assist in the repair and prevention of nerve damage.

In a clinical trial conducted in 2013 [36], 40 individuals diagnosed with depression were split into two groups. The intervention group received daily doses of 1000-3000mg of ALCAR and 600-1800mg of lipoic acid for 12 weeks, while the control group received a placebo. The findings revealed that there wasn't a significant contrast in depressive symptoms between the intervention group and the control group after the 12-week period.

Clinical evidence doesn't strongly support the use of lipoic acid for depression and anxiety disorders. While there's not a lot of evidence backing lipoic acid specifically for treating depression, it serves as a potent antioxidant and contributes to overall health. Its potential lies in indirectly enhancing mental well-being by addressing metabolic chronic ailments in the human body.

Side effects of Alpha Lipoic Acid

ALA is widely regarded as a safe supplement without notable side effects. One study supporting its safety [37-a] suggests that daily doses ranging from 200 to 2400 mg in adults are deemed safe without adverse effects. However, safe dosages for children haven't been established.

While there isn't a defined lethal dose of ALA in humans, studies indicate that high doses, around 121 mg per kilogram of body weight daily, are linked to alterations in liver enzymes and function [37-a]. Consequently, excessive ALA intake might lead to detrimental side effects, more research is needed to determine toxicity.

Because of the physiological impact of ALA, it's advisable to seek advice from your doctor before taking it if you have the following conditions:

Liver disease, Regular heavy alcohol consumption, Individuals with diabetes (ALA is recognized to lower blood sugar), Thyroid disease, or Thiamine deficiency

Moreover, if an allergic reaction such as rash, nausea, or vomiting occurs, discontinuation of ALA usage should be immediate.

Dosage:

In general, there are few serious side effects from high-dose lipoic acid administration. research shows that adults can take up to 2,400 mg without harmful side effects.[38]

The appropriate dosage of lipoic acid (alpha-lipoic acid or ALA) can vary depending on the purpose for which it is being used and individual factors.

1. For General Antioxidant Support:

• Typical dosage: 100 to 300 milligrams (mg) per day.

• Lipoic acid is often used as a general antioxidant to help combat oxidative stress in the body. This dosage range is commonly recommended for overall health maintenance.

2, For Cognitive Health and Mental Health:

• Dosage may vary: Studies investigating lipoic acid's potential benefits for cognitive and mental health have used a range of doses, often between 300 and 600 mg per day.

• Consult with a healthcare professional if you are considering lipoic acid for cognitive or mental health concerns.

Summary:

Lipoic acid is a crucial cellular antioxidant with the capacity to diminish inflammatory reactions. It has been subject to research for its possible advantages in promoting mental health. Here are some potential impacts on mental well-being:

REF:
[1]Lipoic acid". Micronutrient Information Center, Linus Pauling Institute, Oregon State University, Corvallis. 1 January 2019. Retrieved 5 November 2019.

[2]Durrani, AI; Schwartz, H; Nagl, M; Sontag, G (October 2010). "Determination of free [alpha]-lipoic acid in foodstuffs by HPLC coupled with CEAD and ESI-MS". Food Chemistry. 120 (4): 38329–36. doi:10.1016/j.foodchem.2009.11.045.

[3]Lodge JK, Youn HD, Handelman GJ, et al. Natural sources of lipic acid: determination of lipoyllysine released from protease-digested tissues by high performance liquid chromatography incorporating electrochemical detection. J Appl Nutr. 1997;49(1 & 2):3-11.

[4]Nguyen H, Gupta V. Alpha-Lipoic Acid. [Updated 2022 Sep 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK564301/

[5]Rochette L, Ghibu S, Richard C, Zeller M, Cottin Y, Vergely C. Direct and indirect antioxidant properties of α-lipoic acid and therapeutic potential. Mol Nutr Food Res. 2013;57(1):114-125. https://doi.org/10.1002/mnfr.201200608

[6]Irwin C. Gunsalus http://www.nasonline.org/member-directory/deceased-members/20001396.html

[7]Berkson B. M. (1979). Thioctic acid in treatment of hepatotoxic mushroom (Phalloides) poisoning. The New England journal of medicine, 300(7), 371. https://doi.org/10.1056/NEJM197

[8]Reed, LJ (October 2001). "A trail of research from lipoic acid to alpha-keto acid dehydrogenase complexes". Journal of Biological Chemistry. 276 (42): 38329–36. doi:10.1074/jbc.R100026200. PMID 11477096

[9]Superfoodly (2020), Top 10 List of Foods High In Alpha Lipoic Acid (ALA),https://superfoodly.com/top-10-list-of-foods-high-in-alpha-lipoic-acid-ala/

[10Lipoic Acid] https://lpi.oregonstate.edu/mic/dietary-factors/lipoic-acid

[11]Elangovan S, Hsieh TC. Control of cellular redox status and upregulation of quinone reductase NQO1 via Nrf2 activation by alpha-lipoic acid in human leukemia HL-60 cells. Int J Oncol. 2008;33(4):833-838.

[12]Smith AR, Shenvi SV, Widlansky M, Suh JH, Hagen TM. Lipoic acid as a potential therapy for chronic diseases associated with oxidative stress. Curr Med Chem. 2004;11(9):1135-1146.

[13]Packer L, Cadenas E. Lipoic acid: energy metabolism and redox regulation of transcription and cell signaling. J Clin Biochem Nutr. 2011 Jan;48(1):26-32. doi: 10.3164/jcbn.11-005FR. Epub 2010 Dec 29. PMID: 21297908; PMCID: PMC3022059.

[14]Golbidi S, Badran M, Laher I. Diabetes and alpha lipoic Acid. Front Pharmacol. 2011 Nov 17;2:69. doi: 10.3389/fphar.2011.00069. PMID: 22125537; PMCID: PMC3221300.

[15]Jones W, Li X, Qu ZC, Perriott L, Whitesell RR, May JM. Uptake, recycling, and antioxidant actions of alpha-lipoic acid in endothelial cells. Free Radic Biol Med. 2002;33(1):83-93. http://dx.doi.org/10.1016/S0891-5849(02)00862-6

[16]  Kozlov AV, Gille L, Staniek K, Nohl H. Dihydrolipoic acid maintains ubiquinone in the antioxidant active form by two-electron reduction of ubiquinone and one-electron reduction of ubisemiquinone. Arch Biochem Biophys. 1999;363(1):148-154. https://doi.org/10.1006/abbi.1998.1064

[17]  May JM, Qu ZC, Mendiratta S. Protection and recycling of alpha-tocopherol in human erythrocytes by intracellular ascorbic acid. Arch Biochem Biophys. 1998;349(2):281-289. https://doi.org/10.1006/abbi.1997.0473

[18]  Upston JM, Terentis AC, Stocker R. Tocopherol-mediated peroxidation of lipoproteins: implications for vitamin E as a potential antiatherogenic supplement. Faseb J. 1999;13(9):977-994. https://doi.org/10.1096/fasebj.13.9.977

[19]Jacob S, Rett K, Henriksen EJ, Haring HU. Thioctic acid--effects on insulin sensitivity and glucose-metabolism. Biofactors. 1999;10(2-3):169-174. https://doi.org/10.1002/biof.5520100212

[20]Akbari M, Ostadmohammadi V, Lankarani KB, et al. The effects of alpha-lipoic acid supplementation on glucose control and lipid profiles among patients with metabolic diseases: A systematic review and meta-analysis of randomized controlled trials. Metabolism. 2018;87:56-69. https://doi.org/10.1016/j.metabol.2018.07.002

[21]Choi, KH., Park, MS., Kim, HS. et al. Alpha-lipoic acid treatment is neurorestorative and promotes functional recovery after stroke in rats. Mol Brain 8, 9 (2015). https://doi.org/10.1186/s13041-015-0101-6

[22]Monroy Guízar EA, García Benavides L, Ambriz Plascencia AR, Pascoe González S, Totsuka Sutto SE, Cardona Muñoz EG, Méndez-Del Villar M. Effect of Alpha-Lipoic Acid on Clinical and Neurophysiologic Recovery of Carpal Tunnel Syndrome: A Double-Blind, Randomized Clinical Trial. J Med Food. 2018 May;21(5):521-526. doi: 10.1089/jmf.2017.0056. Epub 2018 Jan 22. PMID: 29356576.

[23]Ziegler D, Low PA, Litchy WJ, et al. Efficacy and safety of antioxidant treatment with alpha-lipoic acid over 4 years in diabetic polyneuropathy: the NATHAN 1 trial. Diabetes Care. 2011;34(9):2054-2060. https://doi.org/10.2337/dc11-0503

[24]Ziegler D, Low PA, Freeman R, Tritschler H, Vinik AI. Predictors of improvement and progression of diabetic polyneuropathy following treatment with alpha-lipoic acid for 4 years in the NATHAN 1 trial. J Diabetes Complications. 2016;30(2):350-356. https://doi.org/10.1016/j.jdiacomp.2015.10.018

[25]Ou P, Tritschler HJ, Wolff SP. Thioctic (lipoic) acid: a therapeutic metal-chelating antioxidant? Biochem Pharmacol. 1995;50(1):123-126. https://doi.org/10.1016/0006-2952(95)00116-H

[26]Suh JH, Zhu BZ, deSzoeke E, Frei B, Hagen TM. Dihydrolipoic acid lowers the redox activity of transition metal ions but does not remove them from the active site of enzymes. Redox Rep. 2004;9(1):57-61. http://dx.doi.org/10.1179/135100004225003923

[27]Suh JH, Moreau R, Heath SH, Hagen TM. Dietary supplementation with (R)-alpha-lipoic acid reverses the age-related accumulation of iron and depletion of antioxidants in the rat cerebral cortex. Redox Rep. 2005;10(1):52-60. https://doi.org/10.1179/135100005X21624

[28]Yamamoto H, Watanabe T, Mizuno H, et al. The antioxidant effect of DL-alpha-lipoic acid on copper-induced acute hepatitis in Long-Evans Cinnamon (LEC) rats. Free Radic Res. 2001;34(1):69-80. http://dx.doi.org/10.1080/10715760100300071

[29]Choi KH, Park MS, Kim HS, Kim KT, Kim HS, Kim JT, Kim BC, Kim MK, Park JT, Cho KH. Alpha-lipoic acid treatment is neurorestorative and promotes functional recovery after stroke in rats. Mol Brain. 2015 Feb 11;8:9. doi: 10.1186/s13041-015-0101-6. PMID: 25761600; PMCID: PMC4339247.

[30]Packer L, Tritschler HJ, Wessel K. Neuroprotection by the metabolic antioxidant alpha-lipoic acid. Free Radic Biol Med. 1997;22(1-2):359-78. doi: 10.1016/s0891-5849(96)00269-9. PMID: 8958163.

[31]Paradells-Navarro S, Benlloch-Navarro MS, Almansa Frias MI, Garcia-Esparza MA, Broccoli V, Miranda M, Soria JM. Neuroprotection of Brain Cells by Lipoic Acid Treatment after Cellular Stress. ACS Chem Neurosci. 2017 Mar 15;8(3):569-577. doi: 10.1021/acschemneuro.6b00306. Epub 2016 Dec 9. PMID: 27935686.

[32]Zhao RR, Xu F, Xu XC, Tan GJ, Liu LM, Wu N, Zhang WZ, Liu JX. Effects of alpha-lipoic acid on spatial learning and memory, oxidative stress, and central cholinergic system in a rat model of vascular dementia. Neurosci Lett. 2015 Feb 5;587:113-9. doi: 10.1016/j.neulet.2014.12.037. Epub 2014 Dec 19. PMID: 25534501.

[33]Schreibelt G, Musters RJ, Reijerkerk A, et al. Lipoic acid affects cellular migration into the central nervous system and stabilizes blood-brain barrier integrity. J Immunol. 2006;177(4):2630-2637. http://dx.doi.org/10.4049/jimmunol.177.4.2630

[34]Yang T, Xu Z, Liu W, Feng S, Li H, Guo M, Deng Y, Xu B. Alpha-lipoic acid reduces methylmercury-induced neuronal injury in rat cerebral cortex via antioxidation pathways. Environ Toxicol. 2017 Mar;32(3):931-943. doi: 10.1002/tox.22294. Epub 2016 Jun 14. PMID: 27298056. http://dx.doi.org/10.1002/tox.22294

[35]Çekici, Hande & Bakirhan, Yunus. (2018). Potential Therapeutic Agent In Psychiatric And Neurological Diseases: Alpha Lipoic Acid. Acta Psychopathologica. 04. 10.4172/2469-6676.100165. http://dx.doi.org/10.4172/2469-6676.100165

[36] Brennan BP, Jensen JE, Hudson JI, Coit CE, Beaulieu A, et al. (2013) A placebo-controlled trial of acetyl-l-carnitine and α-lipoic acid in the treatment of bipolar depression. J Clin Psychopharmacol 33: 627-635. http://dx.doi.org/10.1097/JCP.0b013e31829a83f5

[37-a]Cremer DR, Rabeler R, Roberts A, Lynch B. Safety evaluation of alpha-lipoic acid (ALA). Regul Toxicol Pharmacol. 2006 Oct;46(1):29-41 https://doi.org/10.1016/j.yrtph.2006.06.004

[37]Nguyen H, Gupta V. Alpha-Lipoic Acid. [Updated 2022 Sep 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK564301/

[38]D.R. Cremer, R. Rabeler, A. Roberts, B. Lynch, Safety evaluation of α-lipoic acid (ALA), Regulatory Toxicology and Pharmacology, Volume 46, Issue 1, 2006, Pages 29-41, ISSN 0273-2300, https://doi.org/10.1016/j.yrtph.2006.06.004.