This is part II of  “Should we obtain our antioxidants from food or from supplements?”  

We will address the main questions about the consumption of antioxidant supplements, the pills and capsules containing some form of the particular antioxidant desired, Vitamin C, Glutathione,  etc.

We will now discuss the many aspects of food supplementation.

In Part (I),  We discuss the Reduction-Oxidation (Redox) chemical reactions that have to occur in most living creatures. But the Redox processes create free radicals, molecules with unpaired electrons that cause the radicals to be highly chemically reactive. Those free radicals then can, and do, cause oxidative stress, which is damaging to many body tissues. So you can reinforce your body’s natural defenses by eating food rich in antioxidant compounds, vitamins, and phytochemicals

Then again you might also  think about consuming supplements.

  1. Can your body tell the difference between food derived antioxidants, natural supplements, or supplements synthesized in a laboratory?
  2. What does the “shotgun” approach of multivitamins accomplish?
  3. Who should take what?  How much?
  4. Capsule?  Pill? How big of a role do the non-essential ingredients (excipients)  play in the absorption of the supplement?
  5. Any safety issues about supplementation of specific antioxidants or multivitamins?

How do you want your antioxidant packaged?

1 .0 Difference between food derived antioxidants, natural supplements, or synthesized supplements
1.1  Natural  antioxidants in their natural package
Our example here will be the apple
Although this was the subject treated in Part (I) of this article, let me add a link that will illustrate our apple vs. supplements photo:  Silvina Lotito works for the Linus Pauling Institute at Oregon State. She put out an article [1] that illustrates the complexity of the various nutrients interaction in  the apple.
Quoting her: “…However, these [antioxidant] flavonoids are poorly absorbed into the bloodstream. We found that the consumption of apples by volunteers resulted in a large increase in the antioxidant capacity of their plasma, indicating that something other than flavonoids may be responsible. Our further investigations showed that fructose, a fruit sugar, in apples stimulated the production of uric acid in the body, which provided the plasma antioxidant capacity…”
It so happens that uric acid is one of the most powerful antioxidant your body has. But that brings about another question: does that mean that fructose is good for you? Dr Lotito points out that although fructose as a food additive has serious issues, in fruits it is probably OK. But there is more, uric acid is a wonderful antioxidant that might have benefits against multiple sclerosis(!) and other inflammations. Fine and dandy if you do not have gout…
Folks, …things are not as simple as we would hope even about the humble apple.
1.2 A natural antioxidant in a supplement type package
Our example of “natural” supplement based on phytochemicals will be Protandim, because of its large following.  Protandim is a commercial supplement created by the LifeAdvantage company and contains per capsule [2] :
  • Milk thistle (Silybum marianum) extract (225 mg)
  • Bacopa (Bacopa monniera) extract (150 mg)
  • Ashwagandha (Withania somnifera) root (150 mg)
  • Green tea (Camellia sinensis) extract (75 mg)
  • Turmeric (Curcuma Ionga) extract (75 mg)
Since its from plants, the content knowledge of such a mixture is only as good as the chemical analysis of these extracts.  The benefits of Curcumin are well established [3], but the claims of Protandim are rather astounding.   Here is an infomercial  this video, from YouTube:

Although positive research on Protandim has been published in credible journals [4], the broad claims have drawn some skepticism [4].  One needs to understand the interaction and synergy of the multi-compound mixture. Good luck… But Protandim seems to have a growing following in natural healing circles.
We hope the Prorandim video illustrated the issues in creating and marketing a super “phytochemical” nutient compound with antioxidant properties.
Note the compound extraction method vary from just evaporating or freeze drying and encapsulating , to solvent extraction. (wikipedia)
  • Dry extracts are extracts of plant material which are evaporated into a dry mass. They can then be further refined to a capsule or tablet.
  •  Nebulisates Nebulisate is a dry extract created by freeze-drying.
  • Liquid extraction is a much more targeted method of extracting a particular compound from a plant [4]. It is  is done using solvents, and the type of solvent depends on the particular compound you want to extract.   Polar solvents include ethanol, methanol and water ; Medium polar  will include ethyl acetate , acetone and dichloromethane; non polar solvents toluene, chloroform, and hexane solvents
[Note about polarity: It is an electrical  property. The dielectric constant of the solvent provides a rough measure of a solvent’s polarity.The dielectric constant measures the solvent’s ability to reduce the field strength of the electric field surrounding a charged particle immersed in it. (Wikipedia/solvents)]
I am not sure  liquid extraction produces an appetizing fully “natural” product.  Getting to a natural compound from a natural product seems to involve serious chemistry…
1.3  Synthetic  antioxidant in a supplement type package
Here, the main question is: How identical is a synthesized compound to a “natural” one?
The ultimate arbiter of identity in this case is not the chemistry lab where it was produced, but your body.

If it quacks like a duck.....


The lab will assess identity of a compound based on a limited amount of criteria. To have an idea of what is involved in identifying a synthesized compound, we found an article describing the properties of some synthesized biological enzymes [1]:

Quoting: “...Some novel compounds [Schiff bases] were synthesized, and characterized by mass spectroscopy. The compounds were tested for inhibitory activities on human acetylcholinesterase (hAChE), antioxidant activities, acute oral toxicity and further studied by molecular; modeling techniques…

Is such an  identification enough to know all what we need to know about a compound’s identity? If two compounds satisfy mass spectroscopy identity, and tests of certain physico-chemical activities, does that guarantee full identity?

In other words if it walks like a duck, quacks like a duck, it is a duck?  Or perhaps it should have feathers too…

As I said above, identity of the synthesized compound  in the lab is second best to its recognition by your bodyAnd the recognition or identification by your body of a compound it encounters is of extraordinary complexity.

An amazing article in the International Journal “Information Technologies and Knowledge”   illustrates that complexity [9]. This link is not for quick overview, but is bordering the profound. Following this article, here are some of the processes involved in biological molecular recognition:

  1. Molecular folding and docking
  2. Transcriptional regulatory network
  3. Cellular signaling system

Quoting Wikipedia on molecular recognition: “The term molecular recognition refers to the specific interaction between two or more molecules through noncovalent bonding such as hydrogen bonding, metal coordination, hydrophobic forces, van der Waals forces, π-π interactions, electrostatic and/or electromagnetic effects. The host and guest involved in molecular recognition exhibit molecular shape complementarity.

The biochemistry and physical chemistry involved do not lend themselves to “nutshell” descriptions…As you just read, molecular recognition is a science that your body has rather good at , but that researchers are painfully struggling with.

Just look at the 3-D representation of the important antioxidant molecule Glutathione. Imagine other molecules trying to identify it. Then again, perhaps your body can be fooled in accepting it as the real thing, but maybe as in the proverbial duck of our illustration, it missed the lack of feathers. In other words, some  critical Redox reactions could be flawed…Such errors are fairly rare, 1 in a thousands, though, since  your body’s molecular recognition  uses very complex processes represented mathematically as “kinetic proofreading” [18]

Glutathione Antioxidant Molecule

The differences in the actions of synthetic and natural vitamins and compounds is not always in favor of the natural ones. For example vitamin D3 has been shown to be lacking in patients afflicted from a variety of ills. The problem with high vitamin D3 supplementation is that it can bring about hypercalcemia, or too much calcium in the blood. Then again, too much calcium in the blood is a cardiovascular risk for women [13]. So research is turning towards synthetic forms of vitamin D3 to obviate the hypercalcemia issue.

So what is it going to be:

  • Are we going to be of the “laissez- faire ” style and trust our body to find antioxidants like the glutathione in food. Livestrong has a good list. [14]
  • Are we going to go for supplements of the desired antioxidant? This can sometimes run a risk of too much of a good thing. See, for example, what the Hayden Institute [15] says about more than 500 mg of vitamin C supplements/day: It could damage your DNA. Of course this result is controversial [16], and those studies are not recent (1998).  Then again, warnings were also issued about high doses of vitamin E [17].
  • The story about synthetic antioxidants is also that each synthetic and each patient has to be evaluated on their own merits: No blanket statements.
At the very least the concerns about supplementation warrant consulting with a health professional, knowledgeable in supplementation and capable to tailor it to you.

This was part II of  “Should we obtain our antioxidants from food or from supplements? (Part I)”  


  1. Silvina Lotito, LPI Research Associate; “Why Apples are Healthful”; 2004
  2. Wikipedia, Protandim
  3. Consumer’s guide to Turmeric and Curcumin
  4. Journal of Dietary Supplements ; “The Dietary Supplement Protandim Decreases Plasma Osteopontin and Improves Markers of Oxidative Stress in Muscular Dystrophy Mdx Mice.” ; June 2010
  5. sciencebasedmedicine ; Harriet Hall ; “Pursued by Protandim proselytizers”; Oct 2011
  6. Biotecharticles ; Lorato Legkari; July 2010
  7. Molecules 2011, 16, 9316-9330; doi:10.3390/molecules16119316 ; “Synthesis, Characterization, Acetylcholinesterase Inhibition,Molecular Modeling and Antioxidant Activities of Some Novel Schiff Bases Derived from 1-(2-Ketoiminoethyl)piperazines
  8. Wikipedia on Molecular Recognition 
  9. International Journal “Information Technologies and Knowledge”, Vol. 4, Number 1, 2010
  10. University of  Northern Carolina a Charlotte ; Kinetic proof reading
  11. Dipharma ; Technoceuticals; Manufacturing Nutritional Supplements ;
  12. WebMD ; “Study Shows Increased Risk of Heart Attacks for Women Taking Calcium Supplements”
  13. Current Opinions In Investigative Drugs ; “”Vitamin D receptor ligands for osteoporosis.”; 2006
  14. ;”Glutathione sources”
  15. Hayden Institute ;
  16. Linus Pauling institute ; “Does Vitamin C Cause Genetic Damage?” ;
  18. University of Northern Carolina at Charlotte; “Kinetic proofreading” ;




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