The antioxidants vitamin C and lipoic acid both deliver many benefits, but which best fits different clinical settings? Here we will address when each of these antioxidant therapies may be appropriate.
Vitamin C: Broad-based support for immune function, antioxidant status, mood, and tissue health
Although many only think of vitamin C as an immune-supportive agent and chose to take it as a supplement when they’ve fallen ill with a cold, vitamin C has many actions in the body beyond this. The importance of vitamin C was first recognized in the condition of scurvy, a disease associated with malnourishment that was found to be treatable with the consumption of citrus fruit, now known to contain high amounts of vitamin C. The broad symptoms of scurvy including malaise, fever, easy bruising, gum disease, mood changes, muscle pain and poor wound healing shed light on some of the important physiological roles of vitamin C.
Immune function. Supplementation with vitamin C has been observed to shorten the duration and severity of colds, and reduce the risk of developing a cold in people who routinely exercise at a high level of intensity.[i],[ii] As an immune-supportive agent, vitamin C has been shown to improve the function of natural killer cells as well as lymphocyte proliferation and migration to infections.[iii],[iv] Vitamin C also has been shown to have potential benefit in the setting of allergies and asthma as a natural histamine-reducing agent.[v]
Antioxidant. The importance of vitamin C goes far beyond immune function, as vitamin C is an antioxidant and a cofactor in numerous enzymatic reactions. As an antioxidant, vitamin C has been shown to scavenge free radicals, inhibit lipid peroxidation of cellular membranes, and support the body’s levels of other crucial antioxidants such as vitamin E and glutathione.[vi],[vii] Increased levels of oxidative stress may contribute to pathology and dysfunction associated with depression,[viii] metabolic syndrome,[ix] autoimmunity,[x] cardiovascular disease,[xi] and neurodegenerative disorders such as Alzheimer’s disease.[xii]
Mood. Vitamin C is an important cofactor for the synthesis of several hormones and neurotransmitters made in the adrenal gland. Perhaps not surprisingly, the adrenal glands are one of the organs with the highest concentration of vitamin C.[xiii] Ascorbic acid enhances the production of norepinephrine from dopamine,[xiv] while deficiency has been shown to be associated with lower levels of dopamine and serotonin metabolites.[xv] Low plasma ascorbic acid levels have been shown to be associated with major depression.[xvi] Vitamin C has been shown to positively impact symptoms of anxiety and depression in double-blind, randomized, placebo-controlled trials, possibly attributable to its action as an antioxidant.[xvii],[xviii]
Tissue health. Vitamin C is critical for the health of many tissues in the body, as it plays a role in collagen formation. Tissues containing collagen include not only the cartilage, tendons, and ligaments of the joints, but also the skin, gums, blood vessels, bones, intervertebral disks, gut, and muscle. Vitamin C has been shown to stimulate collagen synthesis, particularly that of Type I and Type III collagen.[xix],[xx] Although severe deficiency leading to scurvy is uncommon, symptoms such as easy bruising and oral mucosa changes associated with vitamin C deficiency are still clinically seen.[xxi]
R-Lipoic Acid: Central nervous system protector, mitochondrial nutrient, antioxidant, and chelator
At times, it may be appropriate to bring lipoic acid on board with vitamin C. The use of lipoic acid has been studied in broad array of settings: peripheral neuropathy, insulin resistance, hyperlipidemia, hepatitis, obesity, heavy metal toxicity, Alzheimer’s disease, Parkinson’s disease, traumatic brain injury, migraines, multiple sclerosis, and more.[xxii] As we understand how each of these conditions has aspects of pathology that are attributable to oxidative damage, the potential benefits of this antioxidant should not be surprising. Lipoic acid has been shown to extend the activity of vitamins C and E, also raising ubiquinol and intracellular glutathione.[xxiii],[xxiv] Mechanistically, lipoic acid has been shown to impact endothelial and mitochondrial function – factors which also may play into many of these conditions.[xxv] Lipoic acid crosses the blood-brain barrier which is why its benefits as an antioxidant have been studied in so many neurodegenerative conditions.[xxvi]
What form of lipoic acid is best? Lipoic acid is a molecule with two possible isomers: the R- and the S- form, referred to herein as R-LA and S-LA. Supplementation of lipoic acid as R-LA has been observed to be more bioavailable than the S-LA form.[xxvii] Higher plasma levels of lipoic acid can be achieved when it is supplied as a sodium salt form (sodium R-lipoate) and when taken away from food.[xxviii],[xxix] Maximum plasma levels of lipoic acid with traditional oral dosing (capsules, tablets) have been observed between 10 – 60 minutes after administration, with a plasma half-life of 30 minutes.[xxx],[xxxi] However, some of the effects seen with lipoic acid supplementation are observed up to 24h after oral administration, particularly pertaining to other markers of antioxidant status.[xxxii]
Antioxidant and chelation effects. Lipoic acid is converted to its reduced form dihydrolipoic acid (DHLA) by different enzymes within the mitochondria and cytosol, and from DHLA to further metabolites. As an oxidant couple, lipoic acid and DHLA have both lipophilic and hydrophilic properties.[xxxiii] Both the reduced and oxidized forms have the capability of acting as an antioxidant (with DHLA being the more active form), and together are able to reduce a multitude of free radical species.[xxxiv] The lipoic acid-DHLA duo has evidence as a chelator of redox-active metals in vitro and in vivo.[xxxv] Again, because lipoic acid is able to cross the blood brain barrier, the benefits of it as a chelator are seen in conditions affecting the central nervous system as well.[xxxvi] Not only does lipoic acid support the removal of these damaging metals, it simultaneously supports antioxidant levels in the setting of heavy metal toxicity.[xxxvii] Other stronger chelators such as ethylenediaminetetraacetic acid (EDTA) are thus well supported by the addition of lipoic acid for reducing metal burden while maintaining antioxidant balance during chelation therapy.
[v] Hagel AF, et al. Intravenous infusion of ascorbic acid decreases serum histamine concentrations in patients with allergic and non-allergic diseases. Naunyn Schmiedebergs Arch Pharmacol. 2013 Sep 1;386(9):789-93. View Abstract
[xvii] de Oliveira IJ, et al. Effects of Oral Vitamin C Supplementation on Anxiety in Students: A Double-Blind, Randomized, Placebo-Controlled Trial. Pak J Biol Sci. 2015 Jan;18(1):11-8. View Abstract
[xviii] Amr M, et al. Efficacy of vitamin C as an adjunct to fluoxetine therapy in pediatric major depressive disorder: a randomized, double-blind, placebo-controlled pilot study. Nutr J. 2013 Mar;12(1):1. View Full Paper
[xxv] Liu J. The effects and mechanisms of mitochondrial nutrient alpha-lipoic acid on improving age-associated mitochondrial and cognitive dysfunction: an overview. Neurochem Res. 2008 Jan;33(1):194-203. View Abstract