Alpha Lipoic Acid for Neuropathies

Alpha Lipoic Acid, also written as ALA, lipoic acid, thioctic acid, or α-lipoic acid, is a naturally occurring antioxidant that is found in foods like meat (particularly red meat, liver and organ meats), green vegetables (such as spinach, broccoli, and brussels sprouts), and yeast (especially brewer’s yeast). It is both water and oil soluble, making it incredibly efficient since this enhances its ability to trap free radicals throughout the body, and can pass through the blood-brain barrier. Alpha Lipoic Acid is found in the cell’s mitochondria, where it metabolizes glucose into usable energy (ATP), and has multiple other modes of action as it can: “regenerate other antioxidants such as glutathione, vitamin C, amd vitamin E; serve as a reactive oxygen scavenger; repair oxidative damage; and chelate metallic ions involved in oxidative injury” (Murray & Pizzorno, 2012).  By enhancing the activity of other antioxidants to attack free radicals in the body, it recycles and re-powers them to help trap free radicals. This takes the burden off of nerves while at the same time it promotes their healing.  Alpha Lipoic Acid is limited by its lifespan, solubility, bioavailability (about 30% orally), and instability in the stomach. However, advanced formulations of ALA have improved its efficacy, especially intravenous (IV) therapy.

While our bodies need Alpha Lipoic Acid for metabolic functions, in large doses it can have a therapeutic effect. Studies have shown that ALA used medicinally can help treat chronic illness resulting from oxidative stress by suppressing inflammatory cytokines, preventing inflammatory cells from entering the central nervous system and, in patients who are diabetic, enhancing vasodilation. Oxidative stress “is one of the fundamental causes of functional degeneration, autophagy and apoptosis leading to cytotoxicity and loss of cell survival, often due to exposure to xenobiotics, pollutants, heavy metals, and other environmental and endogenous toxicants. α-LA and DHLA can react with these molecules to strengthen the primary antioxidant defense system during cell injury” (Bjørklund, G et al., 2019). Alpha Lipoic Acid plays the role of healer by reinvigorating antioxidants, and janitor in getting rid of free radicals and heavy metals.

For over twenty years, ALA has been prescribed in Germany to treat neuropathies, which are nerve disorders that result when nerves become damaged or diseased. There are two kinds of neuropathies that ALA has been clinically shown to help. The first is peripheral neuropathy, which is a pathology that applies to all of your nerves except the brain and spinal cord. Diabetic neuropathic is a common type of peripheral neuropathy, but it can also be caused by certain diseases, cancer, shingles, Lyme disease, autoimmune diseases, alcoholism, some medications, and malnutrition. This neuropathy causes numbness, tingling, pain, burning sensations, and poor coordination. There are instances of peripheral neuropathy caused by heavy metal toxicity. Clinically, Alpha Lipoic Acid can be helpful as “studies show ALA binds with toxic metals, such as mercury, arsenic, iron, and other metals that act as free radicals” (Mount Sinai, 2023).

The second type of neuropathy that ALA can help is autonomic neuropathy, which is nerve damage to internal organs such as the heart and gastrointestinal system that affects unconscious processes, such as blood pressure and heart rate, urination and bowel movements. Autonomic neuropathy is a result of injuries or infections, as well as diseases like multiple sclerosis, Parkinson’s Guillain Barré syndrome, diabetes, or alcohol abuse. Manifestations include numbness and tingling, heartburn, acid reflux, lightheadedness, issues urinating or defecating, sexual dysfunction, and sweating. ALA has not yet been studied in-depth for focal neuropathy (when a single nerve is compressed), or cranial neuropathy, which can cause vision problems, palsy, issues with eye and mouth movement. Due to similar pathophysiological mechanisms present in all neuropathies, it may have a positive therapeutic effect on these forms as well.

Alpha Lipoic Acid can be taken as a supplement orally or intravenously, with clinical efficacy ranging from 300-2400 mg per day. Notably, “when taken with avocado/soybean unsaponifiables, ALA is shown to significantly suppress prostaglandin E-2 production, a key cytokine in the pathogenesis of inflammation” (Nguyen & Gupta, 2022). Side effects are rare and mild, and can include fatigue, skin rash, insomnia, and gastrointestinal issues. Since ALA has an effect on blood glucose, those with diabetes, glucose intolerance, or low blood sugar should consult with their healthcare provider first. Other contraindications include diabetes, chemotherapy and thyroid medication, or those with a Vitamin B1 deficiency. In addition to the neuroprotective properties that this oxidative stress scavenger holds, there is promising clinical evidence for its use in other conditions including cardiovascular & cognitive illness, anti-aging, anti-inflammatory, and cancer prevention.

References

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Bjørklund, G., Aaseth, J., Crisponi, G., Rahman, M. M., & Chirumbolo, S. (2019). Insights on alpha lipoic and dihydrolipoic acids as promising scavengers of oxidative stress and possible chelators in mercury toxicology. Journal of inorganic biochemistry, 195, 111–119.

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Morini, M., Roccatagliata, L., Dell’Eva, R., et al. (2004). a-lipoic acid is effective in prevention and treatment of experimental autoimmune encephalomyelitis. Journal of Neuroimmunology. 148:146-153.

Mount Sinai. (2023). Alpha-lipoic acid. Mount Sinai Health System. Retrieved March 6, 2023, from https://www.mountsinai.org/health-library/supplement/alpha-lipoic-acid

Muller, L. & Menzel, H. (1990). Studies on the efficacy of lipoate and dihydrolipoate in the alteration of cadmium2+ toxicity in isolated hepatocytes. Biochim Biophys Acta. 1052(3):386-91.

Murray, M. T., & Pizzorno, J. E. (2012). The encyclopedia of natural medicine. New York, NY: Atria Books.

Nguyen H. & Gupta V. (2022). Alpha-Lipoic Acid. Treasure Island, FL: StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK564301/

Schriebelt, G., Musters, R.J, Reijerkerk, A., et al. (2006). Lipoic acid affects cellular migration into the central nervous system and stabilizes blood-brain barrier integrity. The Journal of Immunology. 177:2630-2637.

Ziegler, D., Reljanovic, M., Mehnert, H., & Gries, F. (2009). Α-lipoic acid in the treatment of diabetic polyneuropathy in Germany: Current evidence from clinical trials. Experimental and Clinical Endocrinology & Diabetes, 107(07), 421–430. https://doi.org/10.1055/s-0029-1212132

Ziegler, D., Low, P. A., and Boulton, A. J. M. (2011). Antioxidant treatment with alpha-lipoic acid in diabetic polyneuropathy: a 4-year randomized double-blind trial (NATHAN 1). Diabetologia 50, S63.

Ziegler, D., Schatz, H., Conrad, F., Gries, F. A., Ulrich, H., and Reichel, G. (1997). Effects of treatment with the antioxidant alpha-lipoic acid on cardiac autonomic neuropathy in NIDDM patients. A 4-month randomized controlled multicenter trial (DEKAN Study). Deutsche Kardiale Autonome Neuropathie. Diabetes Care 20, 369–373.