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28 Apr 2020

Ascorbic Acid versus Sodium Ascorbate

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A great deal of information circulates about ascorbic acid and various forms of it which are available. Thoughts as to its chemistry, absorption, and bioavailability and other factors are debated more so in the arena of social media and less so in the scientific community.

In this blog, I will address the difference between ascorbic acid (ASC) and sodium ascorbate (NaASC) to a small degree in their oral use and to a larger degree in their intravenous (IV) use.

Ascorbic acid is an organic acid with a ring structure similar to glucose. It mainly exists in two forms in humans L-ascorbate (reduced form – ASC) and Dehydroascorbate (oxidized form- DHA). (To be complete there is an intermediate molecule the ascorbate radical which has one more electron than DHA, and one less than ASC, but it converts to DHA in milliseconds normally.) As such it absorbs partly via GLUT transporters but also via specific “vitamin c” transporters of the SVCT family. The GLUT family transport DHA via facilitated diffusion into cells (where DHA must be reduced to ASC to be in its antioxidant state) and the SVCT family transport ASC directly into cells via sodium-dependent co-transporters. [PMID: 11396616] In the intestine this difference between DHA being absorbed via facilitated diffusion at the GLUT receptor family and ASC by either GLUT or the sodium-dependent co-transport of SVCT (with a preference for SVCT by ASC). [PMID: 21749321]

Multiple forms of ASC exist for oral use and a few forms for parenteral (usually IV) administration are used. Plain ASC is used as an oral supplement and is acidic but well absorbed. A “fat-soluble” ester form of ASC (ascorbyl palmitate) is used as an oral and topical delivery system for ASC and then “mineral ascorbates” are often promoted as “buffered vitamin c” supplements. (Of note ‘Ester-C’ ™ is actually a mineral and not an ester version of ascorbate).

In oral administration, ASC is well absorbed but some report GI upset and will have fewer GI symptoms with a mineral “buffered” form of ASC. Commonly this is NaASC, Calcium ASC, or mixtures that include one or both of these forms and any number of other mineral ascorbate forms. While there is some idea that ASC versus a mineral ASC have different absorption overall this is likely a minor issue in regard to GI to Plasma uptake overall.

In parenteral use (mainly IV in humans) a misconception exists regarding the use of “Ascorbic Acid versus Sodium Ascorbate” and the superiority of NaASC over ASC in the IV form. In days gone by one could obtain pure ASC and solubilize it and add it to an IV. This led one of my mentors, Dr. Robert Cathcart, to give instructions to physicians regarding how to make a NaASC infusion solution as opposed to a pure (and acidic) ASC IV. This is believed to be (by some) still a necessary distinction to make in modern IV Vitamin C compounding. While it was a consideration years ago for us, in modern IV Vitamin C use in North America the regulations of manufacturing of IV Vitamin C actually render all IV Vitamin C NaASC. Why?

Legally any pharmacy or pharmaceutical manufacturer must follow the guidelines of the United States Pharmacopeia (USP) which allows pH of infusions to be in the range of 4.5 – 8.0 however it is considered the medical standard of care to infuse as close to physiological human pH as possible (with rare exceptions) which is considered in pharmacology literature to be pH 7.4 plus or minus (also expressed as “pH 7 to 8”). [PMID: 12593942] So when considering this and then a pharmacy has a base solution of ASC with a pH PubChem lists it at 2.0 to 3.0 pH range (specifically ASC pH is concentration dependent but 2.0 – 3.0 is the range it falls in) the CANNOT legally make a sterile pure ASC for infusion. They MUST buffer it with sodium bicarbonate and or sodium hydroxide – both of which yield an acceptable pH for USP AND create NaASC. So while the label of IV ASC usually says “Ascorbic Acid for Infusion” or some similar phrase it is actually NaASC. IV ASC in areas controlled by USP rules can only be made and sold as NaASC.

Yes in the early days of Dr. Klenner, Dr. Cathcart, and even me there was an option and distinction between IV ASC and IV NaASC. In modern times you only can infuse NaASC – you cannot purchase it any other way from any US pharmacy. And that has been the case for many years. Those who promote “the only real NaASC for infusion” are generally either selling something, very misinformed about the above or both (I have spoken to many). They even often emphatically invoke Dr. Cathcart’s name as “proof” of their confusion at which point I normally say “I knew Dr. Cathcart did you?” and proceed to tell them the above.

So, for oral use, NaASC as a mineral ascorbate can be great in sensitive stomachs and may have a slight GI absorption advantage over ASC but that absorption claim in and of itself has a number of mitigating factors.

For IV use you can only infuse NaASC.

A resource for extensive scientific updates and data: An extensive publication regarding most aspects of Vitamin C physiology/biology see Padayatty and Levine PMID: 26808119

 

 

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