Vitamin C as L-ascorbate: A New Look at a Master Antioxidant and Detoxifier

It’s easy to become captivated by and excited about the latest emerging nutraceutical product or ingredient and lose sight of the foundational nutrients that fuel essential physiologic processes every day. 

Case in point: Vitamin C. This nutrient was discovered nearly a century ago and is one of the best-researched and most widely used supplements on the market today. While newer nutrients may get the headlines, the l-ascorbate form of vitamin C remains one of the most effective master antioxidants and detoxifying agents in the human body. 

WHAT IS L-ASCORBATE? 

L-ascorbate is the naturally occurring and most physiologically active form of vitamin C. However, before we get ahead of ourselves, let’s clarify the various terms that are used to describe vitamin C including; ascorbic acid, ascorbate, l-ascorbate, d-ascorbate, and reduced ascorbate. 

Ascorbic acid is the scientific name that was given to vitamin C when it was first discovered in the early 1930s. The name comes from the Latin term “scorbutus,” meaning scurvy, prefaced by “a,” meaning no. Thus, ascorbic refers to vitamin C’s ability to prevent scurvy. 

Ascorbic acid is a water-soluble organic acid, and ascorbate is its negatively charged anion. Ascorbic acid and ascorbate are both present in the human body and interconvert with each other. At physiologic pH, ascorbate is the predominant form. 

Dietary supplements can contain either ascorbic acid or mineral ascorbate salts, which include sodium ascorbate, calcium ascorbate, and potassium ascorbate. Mineral ascorbates are less acidic than ascorbic acid, and are thought to be gentler on the stomach and digestive system when taken in large amounts. 

L-ascorbate and d-ascorbate are enantiomers, meaning they are mirror-image molecules of each other. They exist because vitamin C is a chiral molecule. L-ascorbate and d-ascorbate have different three-dimensional structures, and don’t bind or interact with other molecules in the same way. L-ascorbate is the naturally occurring form, and has the greatest physiologic activity. 

Unless specified, dietary supplements that contain ascorbate or ascorbic acid may contain the l-form, the d-form, or both. L-ascorbate is preferred because of its higher physiologic activity. “Reduced ascorbate” means the ascorbate hasn’t been oxidized. Ascorbate readily donates two consecutive electrons to other molecules (i.e., neutralizes free radicals), but this process converts ascorbate to its oxidized forms: semi dehydroascorbic acid and dehydroascorbic acid. These oxidized compounds are relatively stable (making vitamin C an excellent antioxidant), but they need to be regenerated to reduce ascorbate by glutathione or NADPH dependent enzyme systems to be used again. Despite being the preferred form, not all dietary supplements provide ascorbate in its 100 percent reduced form. 

L-ASCORBATE AS A MASTER DETOXIFIER 

L-ascorbate carries out many functions in the human body. It’s a cofactor for the hydroxylation of procollagen and supports neurotransmitter synthesis, iron absorption, immune function, and xenobiotic detoxification. 

The metabolic detoxification of xenobiotics produces highly reactive oxygen species during phase I reactions. If phase II reactions don’t keep pace with phase I, free radical intermediates cause tissue damage. One way that l-ascorbate assists in detoxification is by acting as an excellent reducing agent and potent antioxidant. 

L-ascorbate can react with the superoxide radical and scavenge the hydroxyl free radical. It’s also water-soluble and therefore active in the cytosol, plasma, and other aqueous compartments of the body, but its effects reach beyond these confines. That’s because l-ascorbate regenerates other antioxidants, including tocopherols and coenzyme Q10, which are important scavengers of lipid peroxides in cell membranes. L-ascorbate is called a “chain-breaking” antioxidant because it halts the chain reaction of free radical generation. 

Studies in humans, cell culture, and animals suggest that l-ascorbate can protect against the damaging effects of xenobiotics.

SUGGESTED USE AND DELIVERY CONSIDERATIONS

L-ascorbate is an essential nutrient. But whereas almost all other plants and animals synthesize l-ascorbate, humans do not. 

Only small amounts of l-ascorbate are needed to prevent deficiency, but dosing recommendations vary widely. The United States Institute of Medicine (IOM) has established a recommended daily allowance (RDA) for vitamin C of 75 mg for women and 90 mg for men. The IOM has also established a tolerable upper intake level of 2,000 mg per day, meaning that long-term intakes should not exceed this amount. 

However, l-ascorbate is often used for short periods of time at ranges higher than 2,000 mg per day, perhaps because it has low toxicity. The most common side effects of higher amounts—nausea, diarrhea, and intestinal cramps—result from l-ascorbate’s osmotic effect within the intestinal tract. L-ascorbate also increases absorption of iron and should be used with caution in patients who have iron-storage diseases. 

Delivery method also has an effect on the suggested amount. L-ascorbate can be delivered intravenously (IV), encapsulated in liposomes (liposomal), or nonencapsulated as mineral ascorbates. 

IV administration achieves high serum levels while bypassing gastrointestinal side effects. Liposomal delivery has gained attention in recent years because of evidence that it raises serum levels more quickly and dramatically than nonencapsulated forms. However, research on the pharmacokinetics of liposomal vitamin C is still new, and mineral ascorbates remain a reliable way to deliver ongoing maintenance supplementation of l-ascorbate.