Taking Supplementation Seriously Part III

There is little debate that a balanced diet is the most desirable method for obtaining essential nutrients, but there are cases when the use of supplemental nutrients may be requisite for insuring adequate nutrient intake. When negotiating the vast number of choices in dietary supplements, one criteria for deciding upon a product is whether it contains natural versus synthetic vitamins and minerals.

Synthetic vitamins are pervasive in the marketplace and very inexpensive; their “man-made” nature, however, is objectionable to some consumers. On the other hand, the availability of completely naturally derived vitamins and mineral supplements is very low (even some “food-derived” vitamin/mineral products are made by seeding microbial cultures with synthetic or semi-synthetic vitamins), and are not always as cost-effective as their synthetic counterparts. It’s hard to ignore the additional benefits that a naturally derived calcium like ossein-hydroxyapatite has in promoting bone growth, or the potential of an impure synthetic nutrient finding its way into a multivitamin product. (Although, one must not forget that even “natural” dietary ingredients undergo processing on their journey to the health food store shelf.) But let’s forgo the natural versus synthetic debate, and concentrate instead on the more nutritionally oriented question of biological activity: Will a high quality, synthetically-produced vitamin or mineral supplement metabolically function in an equivalent manner to its natural counterpart, or must a vitamin or mineral be “natural” to work?

Generally speaking, both natural and synthetic vitamin and mineral ingredients can serve as functional nutrient sources. Indeed, it is important to remember that a majority of the research on the health benefits of supplemental vitamins and minerals over the last several decades has been performed using synthetic vitamins and chemically-synthesized salts of essential trace elements. The parity between synthetic and natural vitamins is because, in nearly all cases, they are chemically identical, and are therefore expected to have similar responses in the human body.

Although “food-derived” or “food-matrix” vitamin supplements would seem a superior source of vitamins and minerals, there is little evidence thus far to suggest this is the case. The argument that vitamins are more bioavailable when integrated into a food matrix has not been borne out by scientific data; most vitamins are taken up in the intestines by individual vitamin transporters after they have been released from their food matrix. In some cases, the presence of a food matrix can inhibit vitamin and mineral uptake (for example, biotin, calcium, zinc, and iron uptake can all be affected by food matrices).

Many minerals have complex regulatory systems that regulate their uptake (to take up sufficient levels for health, but to avoid potentially toxic overload). Some (calcium, magnesium) are taken up in their free, ionized form, others (zinc, copper, selenium, iron) can be absorbed as free ions (at a lower efficiency) or bound to dietary amino- or organic-acids (a higher efficiency absorption method). Since minerals are usually freed from their dietary sources before being used in metabolism, to what the mineral was “attached” when is was ingested has little consequence following absorption. Thus, the body doesn’t distinguish between natural mineral salts/ chelates and synthetic mineral salts/chelates; it is more concerned with the free minerals themselves. A larger determining factor in mineral uptake under these circumstances would be mineral solubility (more soluble chelates and salts can be taken up by intestinal transporters with greater ease than less soluble ones). Many are aware of this phenomenon for calcium salts; in individuals with poor digestion (low stomach acid), or when taken between meals, more soluble calcium salts (calcium citrate/malate) are absorbed better than salts with lower solubility (calcium carbonate). In healthy individuals, when taken with meals, the differences in the absorption of calcium salts are not nearly as significant.

Although the natural and synthetic variants of most vitamins and minerals usually behave similarly, there are a couple of well-characterized instances in which the natural version of a vitamin can significantly out perform its synthetic counterpart. In these cases, the disparity in activity arises because the synthetic vitamin is not chemically identical to the natural one, but similar enough to display biological activity, albeit a reduced one.

Vitamin E is one such example. Synthetic vitamin E has a lower biological activity than natural vitamin E (only half the bioavailability according to a recent review), because synthetic E is actually a mixture of several different vitamin E-like compounds, of which only a fraction is the “correct” vitamin E. The reason for this has to do with the vitamin E (alphatocopherol) molecule itself; it is a very difficult molecule to synthesize efficiently in the laboratory. As a result, the end-product of industrial vitamin E synthesis is a mixture of eight different chemical forms (called stereoisomers) of vitamin E: one is the “natural” stereoisomer of vitamin E (also called D-alphatocopherol or sometimes R,R,R-alpha tocopherol), the other seven stereoisomers are similar to natural E, but differ slightly in their chemical structure. These are the L-alpha tocopherols. Our metabolisms have evolved to only fully recognize and utilize the natural stereoisomer of alpha-tocopherol (the Dor R,R,R- form). Thus, mixtures of “correct” and “incorrect” stereoisomers of alpha-tocopherol (as occur in synthetic E) will function with less efficiency than an equivalent amount of pure natural vitamin E. Most of the time, manufacturers that use natural vitamin E in their products will identify it on the label (“natural vitamin E” or “D-alpha tocopherol”). Synthetic E is sometimes labeled as “DL-alpha tocopherol” or simply “alpha tocopherol.”

Another significant difference in activity occurs between vitamin D2 (ergocalciferol; the synthetic, plant-derived vitamin) and vitamin D3 (cholecalciferol; the naturally occurring animal vitamin which can also be semi-synthetically produced from sheep wool grease). Both are equally absorbed, and both can be converted to into 1,25-hydroxyvitamin D (1,25(OH) D), the active form of the vitamin. However, D3 appears to have a more sustained effect on serum vitamin D levels, which amounts to a significant difference in potency (in one study, a 50,000 IU dosage of D2 was equivalent to only about 5000–15000 IU of D3). This does not mean that D2 is not an efficacious nutrient for raising D levels (a large body of evidence suggests therapeutic dosages are effective at treating deficiency); but the large difference in potency should be considered when taking supplemental D2. D2 is currently the only non-animal source of vitamin D, which is makes it the only option for supplementation in vegetarians/vegans. Vitamin D3 is usually labeled as such on product labels.

In short, a quality vitamin/mineral dietary supplement will likely perform as anticipated, regardless of the source of its nutrients (natural versus synthetic). Even in the cases where synthetic versions of vitamins are measurably less “potent” than their natural counterparts (vitamins D and E), the synthetic versions still provide nutriment. (And in the case of vitamin D2, this difference may be an acceptable trade-off for those seeking a vegetarian/vegan vitamin option.) Although there appears to be several factors that may influence the efficacy of a dietary supplement (such as the choice of mineral salts, the inclusion of “active” nutrient metabolites, or the use of enhanced delivery systems), the “naturalness” of the ingredients likely has little impact, at least for most vitamins and minerals.

Kevin M. Connolly, PhD

Kevin M. Connolly, PhD received his bachelor’s degree in anthropology from Brown University, and doctorate in biochemistry and molecular biology from UCLA. Before consulting for the dietary supplement industry, he spent 15 years in basic biochemistry research elucidating such diverse mechanisms as bacterial antibiotic resistance and collagen synthesis. He contributes to several online and print publications, and is a frequent guest on radio health programs throughout the country. When not writing, he teaches undergraduate biochemistry.