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Natural or Synthetic Vitamins

A NATURAL PREDICAMENT                   Feb 2007     


To supplement or not to supplement?  ...Has now been replaced by... How much to supplement and whether natural or synthetic? 

The need for supplemental nutrients in the typical American diet is no longer in question. Oh, you will still find articles and a few Health Professionals who espouse the traditional "you can get all your vitamins out of food" jargon, but that possible reality is unfortunately long gone. Read Survive Alive to discover some of the more compelling reasons. The Natural Predicament's primary focus is to add some clarity to the natural versus synthetic debate.

The dilemma surfaced as science gained the ability to artificially create vitamins in the lab from chemicals. While it is true that vitamins are chemicals, you will soon learn that nature builds some vitamins in a significantly different way than the ones created synthetically in the lab. The scientists could see the differences, but thought the comparison studies showed enough of the same functions to be "good enough" replacements. New research now questions that past judgment position for some vitamins. ref  ref


If scientific proof exists that synthetically produced vitamins can fully subsitute for natural grown vitamins, there is no need to go any further. 

Before you can completely comprehend and accept this new vitamin criteria, the natural vs synthetic issue needs to be addressed. Here is exactly (or close to) what went down in some laboratory as scientists pondered their new creation, the synthetic vitamin. Let's use vitamin E as it presented the scientists with one of their biggest challenges.


Scientists could see that the synthetic vitamin E was a slightly different structure than the natural. In fact, natural vitamin E consists of 8 different family members divided into two groups, tocopherols and tocotrienols. In each group there are four identically named configurations labeled as d'alpha, d'beta, d'delta, and d'gamma. All the molecules formed going to the right.

Looking at the synthetic version of just the alpha tocopherol family member, the only form the scientists wanted to make for reasons to be discussed in a moment, they noticed rather amazingly that while half the molecules formed to the right, same as the natural, the other half formed to the left. So the scientists added a lower case L after the d' (dl' alpha) to symbolize that half of synthetic E molecules formed to the left. But the differences continued, the scientists discovered that there were actually 8 different forms of alpha tocopherol in the new synthetic vitamin E, 7 of which do not exist in nature.

Testing the synthetic against the natural revealed the synthetic had a much lower activity level. So the scientists increased the amount of the synthetic material until the testing activity for this function was nearly identical. 

SIDEBAR: Behind the scene a battle was raging between two ideologies and companies. The company that was producing natural vitamin E with all 8 family members said that the FDA should use it's product as the standard for vitamin E units while the other company that had just created this new synthetic dl'alpha tocopherol acetate only version was lobbying the FDA to get it established as the standard recognized vitamin E unit. Unfortunately, the FDA made a tragic mistake and accepted the synthetic alpha only as the measurement for this new vitamin E international unit.

The FDA decided that one milligram of the synthetic dl'alpha tocopheryl acetate (an esterfied form signified by adding acetate, or acetic acid) would be the standard to equal one vitamin E international unit. To add insult to injury, the FDA did not allow any of the other 7 natural forms of vitamin E to even be labeled as vitamin E or participate in giving vitamin E units. Since the natural d'alpha tocopherol had higher activity, this meant that one milligram of natural d'alpha tocopherol was equal to 1.49 international units. This activity measurement was determined using animal studies. An important point to remember is that half of the synthetic forms to the left, only a mirror image of the natural.

Now, why did the scientists only want to synthetically create just the alpha tocopherol? Analyzing the blood levels of the 8 members of the family of vitamin E, the scientists discovered that only the alpha tocopherol form was able to be detected in significant amounts after a relatively short period of time. And that alpha appeared to possess the majority of the activity being tested. A judgement was made that the other 7 vitamin E family members must not be that important and only the alpha form would be created synthetically, or even given vitamin E activity units (IU).

Why this happened is due to a strange twist of nature. Only the alpha tocopherol form gets attached to a protein carrier moclecule from the liver that aids it transport throughout the body in blood vessels. This is why it is found in higher amounts when measuring just blood. What if the other E factors mostly entered cells and that is why they were not found in blood tests after a short period of time. The largest vitamin E family member in the American diet by percentage (70+%) is gamma tocopherol, not alpha. European diet is about 50/50. Gamma tocopherol can be converted by the body into the alpha form when extra need for alpha arises, but not vice versa. 

Recent research has discovered that the other 7 natural vitamin E family members do have vital functions separate from the alpha tocopherol form and this warrants a new look at how the international units are determined. Also it was discovered that supplementing with just the isolated alpha form, whether natural or synthetic, suppressed the levels and activities of the other 7 vitamin E family members arriving just from food sources.   



Check out this important report on gamma and delta tocopherol "vitamin E" which are NOT in most supplements:

Proc Natl Acad Sci U S A. 2004 Dec 21;101(51):17825-30. Epub 2004 Dec 13.Click here to read Click here to read Links

Gamma-Tocopherol or combinations of vitamin E forms induce cell death in human prostate cancer cells by interrupting sphingolipid synthesis.

Children's Hospital Oakland Research Institute, 5700 Martin Luther King Jr. Way, Oakland, CA 94609, USA. qjiang@purdue.edu

"gamma-Tocopherol (gammaT), the predominant form of vitamin E in diets, but not alpha-tocopherol, the major vitamin E form in tissues and supplements, inhibits proliferation of prostate cancer cells (LNCaP and PC-3) and lung cancer cells (A549). In contrast, at similar concentrations, gammaT has no effect on normal prostate epithelial cells. Combinations of some vitamin E forms, such as gammaT and delta-tocopherol, exhibit additive or synergistic inhibitory effects. In this study, gammaT or its combination with delta-tocopherol induced apoptosis (cancer cell programed die off) in androgen-sensitive prostate LNCaP, but not in androgen-resistant PC-3 cells, by the induction of cytochrome c release... ... Our study demonstrates that gammaT and mixed vitamin E forms induce cell death by interrupting the de novo sphingolipid pathway in a prostate cancer cell line. Thus, certain vitamin E forms may be valuable as anticancer agents."

PMID: 15596715 [PubMed - indexed for MEDLINE]

Which source or form of vitamin E do you now prefer?

Here is one more recent research fact that will cement the deal.

A human study out of Italy recently tested the synthetic against the natural, measuring how much of each it took to raise to equal blood levels in developing fetuses by giving vitamin E to pregnant women. It took almost twice as many units of synthetic. ref Another similar study
Remember that half of the dl'alpha forming to the left in synthetic vitamin E? The placenta which has a greater barrier to transferring nutrients then most other cell types or structures, might recognize the different E forms and prohibit the synthetic left half from entering the fetus. Or, as the last reference mentioned, the liver recognizes the differences and speeds up the elimination from the body of the synthetic. If this isn't enough to convince you, d'alpha tocopherol represents only about 25% of the total amount of vitamin E family members in USA 's diet, with gamma tocopherol at about 70%. Over 90% of vitamin supplements today offer just the alpha tocopherol form and most (over 90%) are synthetic. Typically, 
scientific research uses the synthetic form with only a few using the natrual isolated d' alpha tocopherol vitamin E form. Seldom is the whole vitamin E family complex tested.

In Defense of SYNTHETIC E

Below is a study showing that a synthetic vitamin E plus a gamma natural form had greater influence on stopping cancer cells than the natural d'alpha Tocopherol form. Very interesting. Take this result with caution though since this was only a test tube analysis. And, this application of the synthetic form should only be used under medical supervision, of course.

Mol Nutr Food Res. 2009 Dec;53(12):1573-81.

Anticancer actions of natural and synthetic vitamin E forms: RRR-alpha-tocopherol blocks the anticancer actions of gamma-tocopherol.


Department of Nutritional Sciences, University of Texas at Austin, 78712-1097, USA.


Two naturally occurring dietary sources of vitamin E (i.e. RRR-alpha-tocopherol (alphaT) and RRR-gamma-tocopherol (gammaT)), the manufactured synthetic form of vitamin E, all-racemic-alpha-tocopherol (all-rac-alphaT), as well as a potent antitumor analog of vitamin E, RRR-alpha-tocopherol ether-linked acetic acid analog (alpha-TEA), were assessed for anticancer actions. Data showed that gammaT, all-rac-alphaT, and alpha-TEA but not alphaT or alphaT+gammaT significantly inhibited tumor burden of human MDA-MB-231 cells in nude mice. Immunohistochemical analyses of tumor tissue showed that all-rac-alphaT and alpha-TEA increased apoptosis and decreased proliferation in tumor cells while gammaT was associated with increased tumor cell apoptosis only. In vitro data showed alpha-TEA and gammaT but not all-rac-alphaT or alphaT to inhibit colony formation and induce apoptosis. Anticancer actions of alpha-TEA and gammaT involved death receptor 5 protein upregulation, Survivin protein downregulation and poly (ADP-ribose) polymerase cleavage, all of which were blocked by co-treatment with alphaT. In summary, both gammaT and alpha-TEA exhibited promising anticancer properties in vivo and in vitro, whereas all-rac-alphaT exhibited promising anticancer properties in vivo only. Importantly, alphaT not only failed to exhibit anticancer properties but it also reduced anticancer actions of gammaT in vivo and gammaT and alpha-TEA in vitro.

[PubMed - indexed for MEDLINE] 
PMCID: PMC3008344



Of course synthetic vitamins exhibit some of the same functions as natural vitamins. They obviously are close enough or identical in some vitamins to prevent common deficencies by virture that the synthetic B vitamins eliminated beriberi and pellagra when fortified in wheat flour and white rice. The situation is that there are other factors that need to be addressed with synthetics that make them a poor alternative to natural in some cases. The above story about synthetic vitamin E shows it fails in many of these areas. Other vitamins such as the vitamins B and C do not have as many differences, but there are some. 

The determining factor boils down to how well synthetic vitamins can participate in all the biological activities of natural vitamins. These factors include absorption rates, transportation around body, ability to enter cells, participation in all metabolic processes, and the rate of excretion or breakdown.

Megadosages of synthetic vitamin supplements can block receptors to limit natural vitamin absorption from food. High dosage isolated alpha tocopherol vitamin E suppresses the blood levels of the other 7 vitamin E family members. Synthetic folic acid at high dosages can overwhelm liver processing channels and enter into the blood stream in an "unmetabolished" state affecting the immune system. At lower levels, the liver converts all the synthetic folic acid into the natural form, folate. Copper gets pushed out by too much zinc. High vitamin E is antagonistic to vitamin K levels. More is NOT always better. There are optimal vitamin ranges and higher amounts do not always provide extra benefits.

An often neglected fact between natural and synthetic vitamin E is that when ingested at equally high dosage amounts, the synthetic metabolites are found to be eliminated in the urine at levels 3 times higher than the natural metabolites. A metabolite is the end process element the vitamin converts to as it goes through the body systems. Does this mean it is working at 3 times the rate or is the body trying to get rid of it faster?

Yes, vitamin E represents the greatest difference between the natural form and the synthetic. Most vitamins have less differences, with some like vitamin C barely noticable. But, it only takes one vitamin to falsify the statement "natural and synthetic vitamins are the same." Vitamin K, beta carotene, vitamin D, folic acid, and vitamin A also present differences including different structures.

When there is a choice between natural and synthetic vitamins, pick the natural. Where there are fewer choices, such as for the water soluble B and C vitamins, go conservative and pick the complexes with all the whole B and C family members together until research settles dosage and form issues. The fact that some synthetic vitamins reach toxic levels at a lower level than their natural vitamin counterpart should be food for thought. These and many other factual differences make it impossible to accept the statement, "natural and synthetic vitamins are the same."

SIDEBAR: The ultimate decision maker between natural and synthetic vitamins is to discover the degree that synthetic vitamins participate in all natural body functions. Obviously synthetic vitamin E does not come very close, while some of the B vitamins and vitamin C have few differences, at least at lower dosages. Therapeutic high doses should be monitored by a doctor for counter-indications with other vitamins, medicines and for any potential, yet actually quite few toxicities.

The Natural vs Synthetic Website Jungle

There are many vitamin websites that misuse science to help sell their products. Saying that synthetic vitamins are a waste since they just pass right through is to miss an obvious fact. In order to pass out in urine and turn it yellow, the synthetic B vitamins first have tbe absorbed. A researcher found that at doses about 2.5 mg, most B vitamins start to spill into the urine at increasing amounts. Therefore, a synthetic 5 mg B complex vitamin turning the urine yellow would indicate a significant absorption rate for B2, the vitamin responsible for this yellow color. Absorption rates between natural and synthetic vitamins are not the major issue. Body digestive controls dictate this issue. In both natural and synthetic vitamins, as intake levels increase, absorption percentages rapidly decrease.

Vitamin Synergies

One argument you will find on websites says that a vitamin is really a blend of nutrients and that synthetic isolated vitamins lacking these other nutrients are not really vitamins at all. To a non science person this sounds like a logical point. But to a scientist, this is pure nonsense. The facts are that the chemical structures of natural vitamins have been analyzed and mapped. How well the synthetic vitamin duplicates this structure is the issue, not the other elements it hangs out with in the body to perform various functions. Vitamins combine with other nutrients such as minerals and proteins to form enzymes. These enzymes have vital body functions. The enzyme is not a vitamin, it is an enzyme. One of its parts is a vitamin. 

Another point to explain this concept is that during digestion, many food nutrients, including vitamins, are separated out of any complexes formed. They are isolated to just the simple vitamin sturcture which increases assimilation into the body. "FoodForm" vitamin companies ignore mentioning this fact in their literature. 

So, back to the main question that needs to be addressed; How well do synthetic vitamins participate in body functions compared to natural vitamins from food? The above presented facts give the edge to natural for most vitamins, but not all. Unfortunately, many vitamins in the marketplace that call themselves natural are not really made by nature. 

Is it Natural or is it Synthetic?

How to Read Labels

Item: If source Given Is: It Is:
Vitamin A

Fish Oils
Lemon Grass

If source not given



Vitamin B-Complex Brewers Yeast*
If source not given or chemical name listed (thiamine)
Fortified Yeast

Food Form**


Synthetic added to food
Vitamin B1 (Thiamine) Yeast (can be synthetic fortified)

Thiamine Mononitrate

Thiamine Hydrochloride




Vitamin B2 (Riboflavin) Yeast*
Pantothenic Acid Yeast*, Rice Bran or Liver
Calcium D-Pantothenate
Vitamin B6 (Pyridoxine) Yeast*
Pyridoxine Hydrochloride
Vitamin B12 Liver
Micro-organism fermentation
Cobalamin Concentrate

Yeast* -
Para-aminobenzoic Acid

Aminobenzoic Acid



Folic Acid Yeast* or Liver
Pteroylglutamic Acid
Inositol Soy Beans
Reduced from Corn
Choline Soy Beans
Choline Chloride
Choline Bitartrate
Biotin Liver
Niacin Yeast*
Niacinamide -could be nat or syn

Vitamin C (Ascorbic Acid)

Citrus, Rose Hips, Acerola Berries, Camu

 Ascorbic Acid (corn)
If source not given

(Natural vitamin C is very rare in supplements)



Vitamin D Fish Oils D3
D3 from lanolin oil
D3 UV irradiated cholesterol
D2 Mushrooms specific
Irradiated Ergosteral (Yeast)
Natural processed
Natural processed
Natural processed
Vitamin E Veg Oil, Wheat Germ Oil, or Mixed Tocopherols
d-alpha tocopherol

* dl-alpha tocopherol

Natural processed


Vitamin F Essential Fatty Acids Natural
Vitamin K

Alfalfa, leafy plants

K2 as MK-7 from Natto





*Most yeasts are now fortified with synthetics during growing process, check labels.
**Most "form form" vitamins contain synthetics added during yeast growing cycle.
There are three vitamin K forms:

  • Vitamin K1 natural (phylloquinone, the natural version from green leafy plants,
  • Vitamin K1 synthetic (Phytonadione)
  • Vitamin K2 natural (menaquinones, there are a few different forms listed as MK-4 , MK-7 (survives longer in the body which makes lower dosages preferred)
  • Vitamin K3 synthetic (menaphthone or menadione)


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