Natural Vitamins May Be Superior to Synthetic Ones
Center for Natural Health Research, Down Syndrome-Epilepsy Foundation
1036 W. Grand Avenue,
Grover Beach, CA 93433
Thiel R.J., Natural Vitamins May Be Superior to Synthetic Ones. Medical Hypotheses, 2000; 55(6):461-469
There appears to be a tendency to label those who profess that natural vitamins are better than synthetic ones as quacks. This broad brush label may be stifling legitimate nutrition research. This paper describes physiochemical differences between certain natural and synthetic vitamins, proven clinical advantages of natural vitamins, and some of the effects this labeling may lead to. It concludes that lessons of history as well as modern science support the view that natural vitamins are nutritionally superior to synthetic ones.
Several frequently used nutrition books are leading to a distortion of scientific fact. Some, when discussing the how to spot quacks, include this comment from authors Barrett and Herbert, “They claim that ‘natural vitamins’ are better than ‘synthetic’ ones” [1,2]. Another (which has been used to train many health professionals about nutrition) similarly states, “Quacks claim that ‘natural’ vitamins are better than synthetic ones” . Interestingly some of these same authors have written that the body is designed to handle foods and should get its vitamins from foods [2,4,5].
“Vitamins are organic substances that are essential in small amounts for the health, growth, reproduction, and maintenance of one or more animal species, which must be included in the diet since they cannot be synthesized at all or in sufficient quantity in the body. Each vitamin performs a specific function, hence one cannot replace another. Vitamins originate primarily in plant tissues” . United States Pharmacopoeia (USP) synthetic vitamin isolates are not naturally “included in the diet”, they do not necessarily “originate primarily in plant tissues”, nor have all of them been proven to safely and fully replace all natural vitamin activities. USP vitamins are not food, even though they are often called “natural” and are sometimes added to foods. USP vitamins are synthesized, standardized chemical isolates . In nature vitamins are never isolated: they are always present in the form of food vitamin-complexes [8-10]. This paper will discuss some of the physiochemical differences between natural vitamins and synthetic ones, as well as cite clinical research which suggest that vitamins in a food complex are superior to USP isolated ones.
Bioavailabilty is a Complex Subject
It needs to be understood that the “bioavailability of orally administered vitamins, minerals, and trace elements is subject to a complex set of influences” . Although some health professionals believe, “The body cannot tell whether a vitamin in the bloodstream came from an organically grown cantaloupe or from a chemist’s laboratory” , this belief is misleading because:
1) It does not seem to consider the fact that there are multiple mechanisms which influence the absorption and utilization of most vitamins [5,11-25]).
2) It does not seem to consider the fact that nutrition scientists understand that particle size is an important factor in nutrient absorption even though particle size is not detected by chemical assessment (smaller size is generally better) .
3) It does not seem to consider the fact that, “The food factors that influence the absorption of nutrients relate not only to the nature of the nutrients themselves, but also their interaction with each other and with the nonabsorbable components of food” (there are no natural food components in most USP vitamin formulas) .
4) “The physiochemical form of a nutrient is a major factor in bioavailability” . Nutrients in natural foods and USP vitamins are not always in the same physiochemical form [5,7,18,21,22,23,27-36].
5) Most USP vitamins are crystalline in structure [6,7,27], while most vitamins in food are not (and are actually present in a complex carbohydrates, proteins, and lipids) .
6) Scientists are just beginning to understand the factors influencing nutrient absorption and utilization. It is not unreasonable to expect that additional food factors will be discovered that further distinguish food nutrients from synthetic ones.
Nutrition is a relatively new field, coming into existence only about 100 years ago, and then mainly because of food processing. Humans survived for thousands of years before synthetic vitamins were developed by consuming foods. These foods contained (and generally still contain) natural vitamins [18-23,37,38]. Natural food complexvitamins are in the physiochemical forms which the body recognizes. They generally are not crystalline in structure, contain food factors that affect bioavailability, and appear to have smaller particle sizes . This does not mean that USP vitamins do not have any value (they clearly do), but studies have shown that vitamins in natural food complexes are better than USP isolated vitamins [e.g.12-17,39-46].
Information by Individual Vitamin
It must be emphasized that natural food complexvitamins are not all chemically identical to isolated USP vitamins [5,7,18,21-23,27-36]. Some synthetic USP vitamins are analogues of the natural agents found to have vitamin action [18,32-36]. Some synthetic USP vitamin analogues have been shown to have no vitamin action [18,32,33], some can act as vitamin antagonists [20,33,34], and some can even produce deficiency symptoms of the specific vitamin they are analogues of  (the effects of the USP analogues differ by type). Note: the discussion below generally referes to the vitamins by their common name rather than the chemical name they are sometimes referred to because some of those chemical forms are not naturally found in foods.
Vitamin A The first professional application of natural vitamin A was probably the use of liver by ancient Greek and Egyptian physicians for people with night blindness . Vitamin A exists in foods primarily in the form of retinyl esters, and not retinoic acid [8,18]: it is not a single isolated chemical as synthetic vitamin A is. “The term retinoids refers to both retinol and its natural metabolites as well as to a large number of synthetic analogues that have structural similarities to retinol but may subserve only some (or none) of the functions of natural vitamin A” . Some of the commonly used forms found in synthetic supplements are not naturally found in food .
Some currently utilized synthetic retinoids are suspected of having potential for causing cirrhosis . It has been reported that consumption of more than 10,000 I.U. per day of synthetic vitamin A increased the rate of birth defects, while consumption of natural vitamin A from foods (including betacarotene, a precursor) did not . Retinyl acetate is the major synthetic form of vitamin A and is a vinyl or coal tar at one or more stages of processing (depending upon the manufacturer) . An animal study found that synthetic vitamin A in the form of retinyl acetate significantly reduced vitamin E utilization ; this has not been shown to occur with natural vitamin A [i.e. 18]. An animal study concluded that a natural food complex vitamin A was probably less toxic than a synthetic USP form and was 1.54 times more absorbed into the blood .
Vitamin B1, Thiamin The free vitamin B1 (called thiamin) is a base. When it is synthesized it becomes a solid salt such as thiamin hydrochloride or thiamin mononitrate . Synthetically thiamin is usually marketed as thiamin hydrochloride or thiamin mononitrate  and is a made from Grewe diamine (a coal tar derivative ) processed with ammonia and other chemicals . No thiamin hydrochloride (often listed as thiamin HCL) or thiamin mononitrate is naturally found in food or the body (thiamin pyrophosphate is the predominant form in the body ) . Yeast and legumes are excellent food sources of natural thiamin . “Thiamin is rapidly destroyed above pH 8...the addition of sodium bicarbonate to green beans and peas to retain their color or to dried beans to soften their skins inactivates thiamin” . High heat, x-rays, and UV irradiation also destroy thiamin [51,52]. Thiamin mononitrate tends to be used for food fortification since it is more stable under storage and processing conditions . An animal study found that a natural food complex vitamin B1 was absorbed 1.38 times more into the blood and was retained 1.27 times more in the liver than an isolated USP thiamin hydrochloride .
Vitamin B2, Riboflavin The free vitamin B2 (called riboflavin) is a weak base. When synthesized it becomes an orange amorphous solid . Some synthetic riboflavin analogues have very weak vitaminic activity . Some natural variations, especially in coenzyme forms, occur in plant (including fungal) species . Processing losses are usually not substantial but do occur as the result of leaching the light-sensitive flavins into water ; in addition, one study found that the pasteurization of bovine milk seems to reduce the bound form of riboflavin from 13.6% to 2% . An animal study found that a natural food complex vitamin B2 was absorbed into the blood and was retained 1.92 times more in the liver than an isolated USP riboflavin .
Vitamin ‘B3’, Niacinamide “Niacin is a generic term...the two coenzymes that are the metabolically active forms of niacin (are)...nicotinamide adenine dinucleotide (NAD) and NAD phosphate (NADP)...Only small amounts of free forms of niacin occur in nature. Most of the niacin in food is present as a component of NAD and NADP...nicotinamide is more soluble in water, alcohol, and ether than nicotinic acid...many analogues of niacin have been synthesized, some of which have antivitamin activity ” . Niacinamide (also called nicotinamide) is considered to have less potential side-effects than niacin ; it also does not seem to cause gastrointestinal upset or hepatotoxicity that the synthetic time-released niacin can cause . Beef, legumes, cereal grains, yeast, and fish are significant natural food sources of vitamin B3 . Processing losses for this vitamin are mainly due to water leaching . Synthetic niacin is usually made in a process involving formaldehyde and ammonia . An animal study found that natural food complex niacinamide is 3.94 times more absorbed in the blood than USP niacinamide and 1.7 times more retained in the liver than isolated USP niacinamide .
Vitamin ‘B5’, Pantothenate Pantothenate was once known as vitamin B5 . USP “Pantothenic acid consists of pantoic acid in amide linkage to beta-alanine”, but the vitamin sometimes referred to as B-5 is not found that way in nature . In food it is found as pantothenate; foods do not naturally contain pantothenic acid . “Synthetic D-pantothenate, the active enantiomer is available as a calcium or sodium salt. However, multivitamin preparations commonly contain its more stable alcohol derivative, panthenol” . Producing synthetic pantothenic acid involves the use of formaldehyde . Organ meats, yeast, egg yolks, and broccoli are rich dietary sources of natural pantothenate . Cooking meat and the processing of vegetables lead to significant losses of pantothenate (15-50% and 37-78% respectively) .
Vitamin B6 “An understanding of the various forms and quantities of these forms in foods is important in the evaluation of the bioavailability and metabolism of vitamin B-6”... one of the forms that vitamin B-6 exists is in the form of “5’0-(beta-D-glycopyransosyl) pyridoxine. To date only plant foods have been found to contain this interesting form of vitamin B-6” . Yeast and rice bran contain more natural vitamin B6 than other foods . The most common form in vitamin pills is USP pyridoxine hydrochloride which is not naturally found in food . At least one synthetic vitamin B-6 analogue has been found to inhibit natural vitamin B6 action . Synthetic B6 usually requires formaldehyde in its production . An animal study found that natural food complexvitamin B6 was absorbed 2.54 times more into the blood and was retained 1.56 times more in the liver than an isolated USP form .
Vitamin ‘B9’, Folate The vitamin once known as vitamin M (and also vitamin B9 ) exists in foods as folate (also known as pteroylglutamate) . Initially, natural food complexfolate was given for people with a pregnancy-related anemia in the form of autolyzed yeast; later a synthetic USP isolate was developed . Pteroylglutamic acid, the common pharmacological (USP) form known as folic acid, is not found significantly as such in the body and appears to be absorbed differently than folate . Folic acid is not found in foods, but folate is . Herbert reports a study found “that consumption of more than 266mg of synthetic folic acid (PGA) results in absorption of unreduced PGA , which may interfere with folate metabolism for a period of years” . Fortification with synthetic folic acid has been found to increase consumption for those who already have higher dietary intakes of folate more than those with lower intakes . It is believed that fortification with synthetic folic acid may put a portion of the population at risk for vitamin B12 deficiency , yet all grain products advertised as enriched must (according to the US FDA) be fortified with folic acid . “Foods with the highest folate content per dry weight include yeast, liver and organ meats, fresh green vegetables and some fruits” . Food processing is a concern since “50-95% of folate in food may be destroyed by protracted cooking or other processing such as canning, and all folate is lost from refined foods such as sugars, hard liquor, and hard candies” . An animal study found that a natural food complexfolate was absorbed only 1.07 times more into the blood, yet was retained 2.13 times more in the liver than isolated USP folic acid .
Vitamin B12 Initially natural food complexvitamin B12 was given for people with pernicious anemia in the form of raw liver, but due to cost considerations a synthetic USP isolate was developed . Cyanocobalamin (the common pharmacological/USP form of vitamin B12) is not found significantly as such in the body; it is usually present in reduced metabolically active co-enzyme forms (without the cyanide) often conjugated in peptide linkage [5,64]. According to Herbert (and others) vitamin B-12 when ingested in its human-active form is non-toxic, yet Herbert and Das have warned that “the efficacy and safety of the vitamin B12 analogues created by nutrient-nutrient interaction in vitamin-mineral supplements is unknown” . Some synthetic vitamin B12 analogues seem to be antagonistic to vitamin B12 activity in the body [33,35]. Synthetic B-12 is made through a fermentation process with the addition of cyanide . An animal study found that a natural food complexvitamin B12 was absorbed 2.56 times more into the blood and was retained 1.59 times more in the liver than isolated USP cyanocobalamin .
Vitamin C Ascorbic acid (AA) is not a synonym for vitamin C, though it certainly has vitamin C (antiscorbutic) properties (dehydroascorbic acid is the other biologically active form) [10,65]. Foods generally contain both biologically active forms of vitamin C [10,65,66], yet most synthetic vitamin C only contains isolated ascorbic acid [7,67]. Consuming five servings of fruits and vegetables per day will result in an intake of least 210mg per day of natural vitamin C (the RDA is 60mg, though 200mg has been proposed) .
Jacob has written, “The bioavailability of vitamin C in food and ‘natural form’ supplements is not significantly different from that of pure synthetic AA” . For proof he cites two papers. The first citation is a paper by Mangels (et al) . It is a study that concludes since serum ascorbic acid levels were at similar levels after various vitamin C containing foods and synthetic ascorbic acid were consumed, that the bioavailibility is similar. The study itself appears to be an excellent one, but its conclusions ignore that fact that it may be possible that DHAA or other food constituents associated with natural vitamin C may have positive effects other than raising serum ascorbate levels. The second citation is a study done by Johnson and Luo . This particular study probably should not have been cited as it never compared vitamin C as complexed in food versus synthetic ascorbic acid. It is an excellent paper which compared synthetic ascorbic acid to Ester-C (a commerical blend of sythetic ascorbic acid and select metabolites) and to synthetic ascorbic acid mixed with some bioflavonoids (the authors note a discrepany between their results and those of similar studies by Vinson and Bose where food complexed vitamin C demonstrated improved absorption compared to synthetic ascorbic acid [14,15]. They suggest that the differences may be a function of bioflavonoid concentration--their experiments used only had 1/14th - 1/80th of the amount used by Vinson and Bose [14,15]). The data in this study showed that absorption was minimally better with the product with added bioflavonoids, though the authors concluded the differences were not significant .
Interestingly Levine (et al) has written, that “There are no data for true bioavailability of vitamin C administered with foods or with compounds in foods” . Though this can be debated, this same chapter also states, “Diets with high vitamin C content from fruits and vegetables are associated with lower cancer risk, especially for cancers of the oral cavity, esophagus, stomach, colon, and lung. In contrast, consumption of vitamin C as a supplement in experimental trials had no effect on development of colorectal adenoma and stomach cancer” . Other studies seem to give a reasonable hint about the comparison of vitamin C in foods compared to isolated ascorbic acid [41,69]--they suggest that foods are superior. A human study found that a vitamin C complexed in food was absorbed 1.74 times more into red blood cells than isolated USP ascorbic acid , while another found it to be 1.35 times more absorbed into the plasma . Also, it appears that vitamin C in citrus decomposes more slowly than plain synthetic ascorbic acid; whether this is due to bioflavonoids or other substances found in citrus is unknown 
A human study found that a food complex containing 500mg of vitamin C was 2.16 times more effective in reducing sorbitol in diabetics than was isolated ascorbic acid . One study by Vinson and Howard showed an average decrease of 46.8% in protein glycation after four weeks using 1000mg per day of vitamin C complexed in food , while a study by Davie, Gould, and Yudkin only had a 33% reduction in three months using 1000mg of isolated ascorbic acid per day . An animal study found that after one month of feeding, vitamin C complexed with food (it was not a simple mixture) induced a significant reduction of 77%, 66%, and 40% in plasma total cholesterol, LDL + VLDL, and triglycerides respectively and that USP ascorbic acid or bioflavonoids alone were ineffective (though isolated USP ascorbic acid did raise HDL); this same study also found that the natural food complex vitamin C strongly inhibited atherosclerosis . Another animal study found that vitamin C complexed in food was 41% more effective than isolated ascorbic acid in decreasing galactiol when cataracts were present . These studies suggest that there may be multiple benefits associated with natural vitamin C that are not always apparent when only serum ascorbic acid levels are measured.
Vitamin D “Vitamin D is inherently biologically inactive...1,25-dihydroxyvitamin D” is “the biologically active form of vitamin D”. Vitamin D is not an isolate, it “is a combination of substances” ; USP vitamin D forms are normally isolates. Foods contain complexed, not isolated, vitamin D. “The first vitamin isolated was a photoproduct from the irradiation of the fungal sterol ergosterol. This vitamin was known as D1...vitamin D obtained from irradiation of ergosterol had little antirachitic activity” --in other words, the first synthetic vitamin D did not act the same as natural vitamin D.
“At the time of its identification, it was assumed that the vitamin D made in the skin during exposure to sunlight was vitamin D2”, but it was later learned that human skin produced something called vitamin D3 . It was first believed that provitamin D3 was directly converted to vitamin D3, but that was incorrect. The skin actually contains a substance commonly called provitamin D3; after exposure to sunlight previtamin D3 is produced and it begins to isomerize into vitamin D2 in a process which is temperature dependent, with isomerized vitamin D3 being jettisoned from the plasma membrane into extracellular space. Vitamin D2 was used to fortify milk in the US and Canada for about forty years until it was learned that D3 was the substance which had better antirachitic activity, so D3 has been used for the past twenty years . But vitamin D has many benefits which are unrelated to rickets: B and T lymphocytes have been shown to have receptors for vitamin D similar to those found in the intestines, vitamin D seems to affect phagocytosis, and may even have some antiproliferation effect for tumor cells . It has not been proven that any single USP isolated form of vitamin D has all the benefits as natural occurring forms of vitamin D. (Also, since the vitamin D was not particularly stable, manufacturers used to put in 1.5 to 2 times as much of synthetic vitamin D as they claimed. This led to neonatal problems and hypercalcemia. .) New vitamin D analogues are still being developed: some which may have greater affects on calcium utilization , some even may be helpful for breast cancer --but these really may be pharmacological applications since these analogues are not food. In view of the historical errors in the supplementation with forms of vitamin D, it is reasonable to conclude that additional benefits of natural source vitamin D may be discovered, further distinguishing it from synthetic isolates.
Vitamin E “Synthetic and naturally derived alpha-tocopherol, and their ester forms, are commonly used in vitamin E supplements. These various forms give rise to isomer differences, ester differences and formulation differences that can affect their absorption and subsequent utilization” .Natural vitamin E “as found in foods is [d]-alpha tocopherol, whereas chemical synthesis produces a mixture of eight epimers” .
An article in the Journal of the American Dietetics Association had a large headline which stated, “The natural and synthetic forms of vitamin E deliver equal health benefits to human beings” . It was not a review article. Although it states, “Contrary to findings of studies conducted with animal subjects, human beings appear to be able to absorb the natural and synthetic forms as well”, this conclusion was based upon one human study by Devaraj (et al) . In it, subjects who received large amounts of natural or synthetic vitamin E had equal benefits in inhibiting the oxidation of low-density lipoprotein cholesterol (LDL-C). Although this study has value, it did not prove the premise of the article. Vitamin E has more beneficial effects on the body than simply inhibiting oxidation of LDL-C . Three issues later that same journal posted a smaller piece which stated, “The placenta, the fetal liver, or both are able to discriminate between natural (RRR-) and synthetic (all-rac) alpha-tocopherol; RRR-alpha-tocopherol is transported preferentially over all-rac-alpha-tocopherol...Maternal plasma and lipoproteins and cord plasma obtained at the time of delivery (after 5 to 9 days of supplementation) had higher concentrations of natural than synthetic tocopherol regardless of the vitamin E dose received”, yet strangely it did not declare in large headlines that natural vitamin E was superior to synthetic vitamin E . The Devaraj study is consistent with the results of a human study done by Traber (et al) which found that there was no difference in the absorption and secretion in chylomicrons of various tocopherols, but that there was a preferential enrichment of very low density lipoprotein with RRR-alpha-tocopherol . These studies help demonstrate that although synthetic vitamins have some of the benefits of natural vitamins, they really do not replace all the benefits of natural ones.
It has been written that, “Vitamin E is the exception to the paradigm that synthetic and natural vitamins are the equivalent because their molecular structures are identical”  (vitamin E, as this paper is hypothesizing, is not the only exception). “Synthetic vitamin E is produced by commercially coupling trimethylhydroquinone (TMHQ) with isophytol. This chemical reaction produces a difficult-to-separate mixture” . In foods, natural vitamin E is always found with lipids and other food substances . A human study by Burton (et al) concluded that isolated “natural vitamin E has roughly twice the availability than synthetic vitamin E”  (synthetic vitamin E forms are analogues). A human study by Acuff (et al) found that natural vitamin E was absorbed 3.42 time better than synthetic in cord blood during pregnancy . A human urinary excretion study by Traber (et al) concluded that natural vitamin E was 2.7 times better absorbed than synthetic vitamin E; this study suggests that it seems the body may want to rid itself of the synthetic as quickly as possible . An animal liver study found that a natural vitamin E complexed in foods was 2.6 times more retained than isolated USP d-alpha tocopheryl acid succinate (which is the so-called ‘natural form’ once it is isolated from its food complex) . Another animal study suggests that natural vitamin E has less tumorgenicity than synthetic vitamin E .
Vitamin ‘H’, Biotin Biotin is a water-soluble vitamin once known as vitamin H. “Various biotin derivatives, analogues, and antagonists are known...Most of the biotin of natural products is protein bound” . Crystalline USP biotin is not protein bound. Foods contain the “free, available form of biotin” which is usually protein bound . Egg yolk, liver, and some vegetables are relatively rich in biotin . Synthetic biotin is made from fumaric acid (trans-1,2-ethylene ) .
Vitamin K Many compounds have vitamin K activity, but at least one (K3) may be dangerous . Vitamin K1 (phylloquinone) is how it exists in plants and “there are no reports of toxic effects of phylloquinone at 500 times its RDA” . It is now recognized that menadione (the substance initially known as vitamin K3) “should not be employed any longer as a therapeutic form of vitamin K” (it can cause hemolytic anemia, hyperbilirubinemia, and kernicterus in infants) . Dark green vegetables appear to be the primary food source of vitamin K . There is another form of vitamin K that is found in the diet which is inadvertently formed during hydrogenation of oils called dihydro-vitamin K1; its relative bioavailability is still unknown . However, since the consumption of hydrogenated oils appears to be dangerous , it does not seem that this synthetic form is as good to consume as the form naturally found in unprocessed food (phylloquinone). Some, however, feel that this artificial type of vitamin K may be beneficial for human health .
Food and Food Processing
“In the historic struggle for food, humans ate primarily whole foods or so-called natural foods, which underwent little processing...The nutrient content of food usually decreases when it is processed” . Changes in the production and processing of food has resulted in multiple thousands of deaths in the U.S. [82-84].
Food processing techniques can reduce the amount of every known essential vitamin. The refining of rice reduced B-complex vitamins and initially led to deaths in Asia due to beriberi [4,19]. Even though synthetic USP vitamins are added to white rice, it does not contain the same nutrients as unpolished brown rice (nor does white flour contain the same nutrients as whole flour) [4,85]. The earlier refining of corn meal which reduced natural vitamin B-3 and amino acid levels was so devastating it produced around U.S. 7,000 deaths per year for several decades . The refining of whole grains (including wheat, rice, and corn) has resulted in a dramatic reduction of their natural food complex nutrients[4,85]. The milling of wheat to white flour reduces the natural food complex vitamin and mineral content by 40-60% . Various food processing techniques (including pasteurization of milk) reduce the available vitamin B6 in foods by 10-50% [85,86]. The recently introduced artificial fat olestra (also known as Olean) robs the body of oil soluble vitamins (vitamins A,D,E, and K) and carotenoid antioxidants (betacarotene, lutein, lycopene) [87-89]; the proposed “solution” is to add synthetic USP versions of the vitamins to olestra products [87-89]. Irradiation of meat and other foods “changes the characteristics of food”  and has been found to reduce levels of vitamins A, B1, B6, E, K, and other nutrient levels [6,27,90]. Unknown nutrients may also be affected from food processing. No one yet knows how the combinations of these more recent food processing techniques will effect human health , but it is not likely that they will promote optimal nutrition.
The primary reason that isolated USP vitamins were developed was cost . A secondary reason probably was standardization (it is harder to standardize food), including stability [7,23,27]. Neither reason justifies placing USP isolates on the same health level as natural vitamins as found in foods. Humans would not naturally consume most of the materials used to make and process synthetic vitamins. Actually Herbert raised an interesting point about synthetic vitamins when he wrote, “The misrepresentation that vitamin C, beta carotene, and vitamin E are solely antioxidant ignores that they are in fact redox agents, sometimes antioxidant and sometimes prooxidant, and that in supplement quantities, they have totally non-vitamin chemical activity, some of which may be harmful” ; this combined with Herbert’s earlier comments on synthetic vitamin B12  and synthetic folic acid  suggests that perhaps he has safety and efficacy concerns about synthetic vitamins. As cited earlier, there are reasons to have concerns about the safety and efficacy of many synthetic vitamins.
It should be noted that the concept that substances in foods can be more effective than their USP counterparts is not limited to vitamins. For example, there are “reports of patients with Parkinson’s disease who benefit from meals of broad beans (vicia faba) and that response to vicia faba may even be better than conventional L-dopa medication in some cases. The beans are natural food which contain L-dopa in a physiochemical form different from that of tablet formulations and therefore may have some use in the management of Parkinson motor fluctuations” . Natural beta-carotene was found to significantly decrease serum conjugated diene levels for children exposed to high levels of irradiation, though it is not known if synthetic beta-carotene would provide similar benefits (natural beta-carotene is composed of both all-trans and 9-cis isomers while synthetic is all-trans isomers) . Dietary patterns have been shown to be more effective preventing some of the most common fatal diseases (such as cancer and cardiovascular disease) than consuming synthetic vitamins [i.e.41,95-98]. Actually, many believe that the antioxidant effects of synthetic vitamins cannot match those of natural vitamins [41-45,99-101].
Studies suggest that the bioavailability of natural food complex vitamins is better than that of most isolated USP vitamins [e.g. 12-17,40-46], that they may have better effects on maintaining aspects of human health beyond traditional vitamin deficiency syndromes [15,37,44,45,69,76], and at least some seem to be preferentially retained by the human body [12,46]. It is not always clear if these advantages are due to the physiochemical form of the vitamin, with the other food constituents that are naturally found with them, or some combination [42,95]. Regardless, it seems logical to conclude that for purposes of maintaining normal health, natural vitamins are superior to synthetic ones.
Labeling someone, who after studying the physiological forms and clinical applications of vitamins, concludes that natural ones are superior to synthetics, as a “quack” is irresponsible. It is this type of false science that leads many in the general public to distrust many “health experts” and requires that true researchers sometimes rely on publications which have not been fully “peer-reviewed” . It may even lead to publishing bias (not publishing information which supports the view that natural vitamins are superior to synthetic ones). It also seems logical that it would tend to discourage research (especially if government funded) into advantages of improving our food supply (if synthetics are just as good why bother?). This appears to be dangerous for human health.
Synthetic USP isolates are not the same as natural vitamins complexed in food. Humans would not naturally want to eat many of the substances that are used in the manufacturing of synthetic vitamins. Humans are supposed to eat food  and receive their vitamins from foods . Most people can improve their health by eating health-building whole foods such as fruits and vegetables and whole grains (and consuming less refined carbohydrates) [4,103]. This alone can help increase the consumption of natural vitamins. Vitamin nutrition should come from food or from supplements which are as close to food as possible. Since no one knows everything there is to know about nutrition, it seems logical from both a historical and modern perspective to consume vitamins in the forms found in natural food complexes and not to try to build health based on chemical isolates. It also makes no sense to label those who believe in legitimate science as quacks.
Dr. Thiel recommends and personally takes the vitamins found at Doctors' Research.
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