To understand the difference between natural and synthetic supplements we need to return to the organic chemistry classes we all took in college.  The key components we need to focus on are stereoisomers.  As we all remember, stereoisomers are chemically identical molecules, but with different spatial orientation.  Because of the structure of the carbon atom, chemically identical molecules can have mirror image structures that change the physical properties of the molecule.  This can be thought of as a pair of gloves.  They are materially identical, yet one is for the right hand and one is for the left hand, they are mirror images of each other.  Even though they are materially identical, structurally they are hardly interchangeable, as anyone who has tried to wear a glove on the wrong hand has discovered.

The same is true of most dietary supplements.  Whether you believe in evolution or creation, the results are the same.  Naturally occurring substances have developed so that the synthesizing and the breakdown of nutrients all have the same configuration at any isomeric point.  The process of creating nutrients and the process of metabolism each use enzymes to orient the atoms of each molecule to facilitate the chemical reaction.  That is the definition of an enzyme; that it acts as a catalyst enhancing chemical reactions.

Laboratory created nutrients, especially chemically complex ones, are created using heat or pressure as the catalyst, causing every steroisomeric possibility to be formed equally.  If there is only one stereoisomeric possibility, then the artificial supplement is only 50% as effective as a natural supplement, at best.  If there are several stereoisomers possible, then the effectiveness of the nutrient diminishes rapidly.

Even if the artificial supplement only has one isomeric pair possible, its effectiveness can be much less than 50% of a natural supplement.  This is due to the fact that enzymes usually have an active and inactive configuration.  After an enzyme attaches to a substrate, its physical configuration changes to bring about the chemical reaction.  Once the chemical reaction has occurred the physical configuration of the enzyme again changes releasing the newly formed molecule and freeing up the enzymatic sites for further chemical reactions.  If the opposite isomer binds with an enzyme, it may not be spatially oriented to react with other molecules and binds up the enzyme making it useless.as a catalyst.

This is the reason synthetic vitamins may not only not be effective; they can actually be harmful to patients by binding up enzymes, thus reducing the digestive effectiveness in general.  This will also explain why many studies demonstrate little or no benefit from dietary supplementation.  Anytime you see a study claiming that supplements make no difference, dig deeper and see if the researchers used natural or synthetic supplements.