R-Lipoic Acid - A Crucial Mitochondrial Supplement

Lipoic acid (1,2-dithiolane-3-pentanoic acid) is an organosulfur compound we produce during aerobic metabolism. Lipoic acid is present in nearly all foods we consume but is covalently bound and not readily obtained from food sources. Food consumption of lipoic acid has failed in studies to show any increase of lipoic acid concentration within our plasma or cells. Lipoic acid supplementation is absorbed and improves mitochondrial function, reduces oxidative stress, and relieves excessive inflammation within our body. Lipoic acid is best taken on an empty stomach to enhance absorption (unless you suffer from hypoglycemia, it is best to take it with food because it can reduce blood glucose levels). Finally, the half-life of alpha-lipoic acid is thirty minutes, and the half-life of R-lipoic acid is four to six hours.[1] [2] [3] [4]

Lipoic acid is synthesized from octanoic acid (8-carbon fatty acid) in our mitochondria. Lipoic acid combats cellular degeneration by optimizing energy conversion, preventing the release of excess oxidants within our mitochondria that lead to oxidative stress. Lipoic acid is also an essential cofactor for many different mitochondrial enzymes that catabolize alpha-keto acids and amino acids and catalyze reactions related to mitochondrial energy production. Since fewer oxidants are produced within the electron transport chain, its function and stability are improved. Lipoic acid also neutralizes reactive oxygen species produced within our mitochondria and cells. Finally, lipoic acid prevents the formation and inactivates glycation end products (proteins and lipids that become glycated as a result of exposure to sugars, which are increased in production when blood glucose is elevated (here [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4496742/] is a paper covering advanced glycation and how it causes injury) within our cells, plasma, and mitochondria.[5] [6] [7] [8]

It has also been theorized that lipoic acid repairs oxidative stress by enhancing antioxidant defense systems by activating phase two enzymes within our liver. An example of one of the most important phase two enzymes produced by our body is glutathione transferase. Glutathione transferase’s job within our body is to make glutathione bind to xenobiotics (foreign chemicals within our body that you do not produce; most medicines would be an example of a xenobiotic). Glutathione then directly detoxifies the xenobiotic or binds to it and eliminates it from our body. Glutathione is the “master” antioxidant and detoxifier within our body. Lipoic acid can also regenerate the antioxidants glutathione, vitamin C, vitamin E, and CoQ₁₀, further improving mitochondrial and cellular health. R-lipoic acid is known to increase mitochondrial biogenesis. Finally, lipoic acid may increase glutathione synthesis by increasing the expression of γ-glutamylcysteine ligase, the enzyme that rate-limits glutathione production, increasing the cellular uptake of cysteine, and producing more glutathione.[9] [10] [11] [12]

Lipoic acid has been studied extensively for its use in improving health in people with diabetes. Lipoic acid is believed to be crucial for proper insulin signaling. Insulin is a hormone produced within our pancreas by the islets of Langerhans that regulates blood glucose. The binding of insulin to the cellular insulin receptor triggers the autophosphorylation of tyrosine residues; lipoic acid has been shown to stabilize this reaction, allowing proper cellular glucose intake. In addition, as mentioned above in the text earlier, lipoic acid reduces the formation and inactivates advanced glycation end products, preventing and relieving inflammation and neuropathy in people with diabetes. Finally, lipoic acid may help improve vascular health and promote healthy blood flow by improving endothelium-dependent vasodilation and reducing excessive vascular inflammation in people with diabetes.[13] [14] [15] [16] [17]

Rare side effects from supplementing with lipoic acid include malodorous urine, abdominal upset, vomiting, diarrhea, skin rashes, hypoglycemia, and systemic allergic reactions. These side effects are more commonly witnessed when taking synthetic alpha-lipoic acid (which should only be supplemented for the Cutler protocol) instead of natural R-lipoic acid. Lipoic acid is also similar to biotin in its chemical structure; it is unknown if supplementation of lipoic acid for a long period of time may lead to a biotin deficiency (hair loss, scaly red rash around our mouth, eyes, genital area, and neurologic symptoms are associated with a biotin deficiency). Lipoic acid is also a powerful chelator, so do not take it simultaneously with mineral supplements. If you are mercury burdened and still have deposits within your body (including dental amalgams), avoid supplementing with lipoic acid. Improper use of lipoic acid in someone who is mercury burdened might reposition the mercury deposits to different parts of one’s body (including your brain) and cause worsening health.[18] [19] [20]

Dr. Andrew Cutler (the foremost expert on mercury chelation) and livingnetwork.co.za on lipoic acid and mercury chelation:

“ALA is the most important ingredient in oral chelation. ALA chelates both intracellular and extracellular mercury (and arsenic) – in the brain and in the body – making it essential to successful detox.”

“ALA is a disulfide. It is water and fat soluble which makes it able to pass the Blood Brain Barrier (BBB) and is thus able to clear mercury from the brain and inside the organs. You can successfully clear mercury with ALA alone. ALA is essential to detox. ALA has a half-life of three hours.”

“Ensure your mercury amalgams have been safely removed. You cannot take any chelating substance while you still have mercury amalgams in your mouth, or have exposure to any other source of mercury.”

“If you have removed your mercury amalgams a long time ago, use DMSA on its own for a few months before adding ALA. In this way you can know which supplement is causing a problem if it occurs.”

“The brain will not detox mercury on its own and only over a lifetime would it be able to eliminate it to a small degree. Only ALA is able to allow mercury to be excreted from the brain. People with significant brain mercury will not be able to improve unless they use enough ALA for a long enough time. Those that improve greatly on DMSA alone, do not usually have as much brain toxicity. ALA is excreted mainly through the biliary system (bile ducts) from the liver and into the gastro-intestinal tract and also through the kidneys. This means these pathways of elimination should be flowing well to assist detoxification.”[21]

Finally, lipoic acid contains sulfur, so people with CBS [22] (https://drjockers.com/cbs-mutation-low-sulfur-diet/) polymorphisms or hydrogen sulfide dysbiosis [23] (https://www.fixyourgut.com/sibo-methane-or-hydrogen-dominant-what-is-the-difference/) might have increased side effects when supplementing.

Recommended R-lipoic Acid Supplements

Recommended R-lipoic Acid: GeroNova R-Plus lipoic acid

Other Recommended Brands of R-lipoic Acid: Designs for Health Stabilized R-Lipoic Acid Supreme, Life Extension Super R-lipoic acid

Dosage Recommendations: For the GeroNova R-plus lipoic acid supplement, I recommend taking one softgel when you wake up and one between lunch and dinner. For the Designs for Health Stabilized R-Lipoic Acid Supreme supplement, I recommend taking one capsule when you wake up and one with dinner. I recommend taking one Life Extension Super R-lipoic acid supplement capsule when you wake up. Take your lipoic acid supplement with food if you are prone to hypoglycemia (symptoms of hypoglycemia include shaking, disorientation, a decline in cognitive function, sudden extreme hunger, irritability, and fainting). Skip the second dose if the lipoic acid hinders sleep because it can be too stimulating for some.

[1] https://lpi.oregonstate.edu/mic/dietary-factors/lipoic-acid

[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2756298/

[3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723188/

[4] https://www.ncbi.nlm.nih.gov/pubmed/14551180

[5] https://lpi.oregonstate.edu/mic/dietary-factors/lipoic-acid

[6] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2756298/

[7] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723188/

[8] https://www.hindawi.com/journals/omcl/2013/517045/

[9] https://lpi.oregonstate.edu/mic/dietary-factors/lipoic-acid

[10] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2756298/

[11] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723188/

[12] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3022059/