Natural or Synthetic – It’s Time to Get Real - Brad King, MS, MFS

Natural or Synthetic – It’s Time to Get Real - Brad King, MS, MFS

 How many times have you taken a vitamin and wondered, is this really natural? If you’re like most, probably never. The reason being most people would be inclined to believe that all vitamins are natural - but are they?

The vitamins that we consume can easily be classified into the following two categories:

1) "naturally derived" and

2) "synthetically derived."

These terms indicate whether these compounds are produced through natural biological processes (i.e., by a plant) or through industrial chemical methods. Believe it or not, well over 95% of commercially available vitamin compounds (including almost all multivitamin formulas) are created 100% synthetic, created through extensive chemical manipulation and are delivered in isolated forms. Nutrients in nature are almost always synergised with naturally occurring micronutrient cofactors, which are the soul of the nutrient kingdom.

The Problem with Synthetic Nutrients

When a supplement is synthetically derived, it often requires many stages of chemical processing in order to imitate its natural counterpart[1]. Even though the synthetic nutrient(s) looks similar to its natural cousin, it differs significantly in the way it performs inside a living organism, in this case you! One of the major debates regarding synthetic vs. naturally derived (from real fruits, vegetables and herbs) vitamins is in the body's ability to recognize, absorb, and utilize them effectively[2]. Studies suggest that naturally derived vitamins typically offer superior bioavailability, absorption and bio-compatibility compared to their synthetic counterparts[3].

For example, let's consider Vitamin E. Natural Vitamin E (d-alpha-tocopherol) has been shown in studies to be more bioavailable, safer, and retained longer in body tissues than its synthetic form (dl-alpha-tocopherol)[4]. Similarly, research indicates that the natural form of Vitamin C (L-ascorbic acid) has a higher bioavailability than its synthetic equivalent (ascorbic acid)[5].

Folic Acid – Far from Natural

To further explain the difference between natural and synthetic versions of vitamins, let’s take a look at folate or vitamin B9, which is crucial for DNA synthesis and repair, cell division, and growth, especially during pregnancy and infancy. The synthetic form of folate is folic acid. Ongoing research suggests the possibility of negative health effects through continuous supplementation of this synthetic form[6]. In order to understand why, let’s look at how each form is metabolized. The natural form, folate is readily absorbed and used by the body as it is easily converted into its active form, 5-methyltetrahydrofolate (5-MTHF), in the digestive system before entering the bloodstream[7].

5-MTHF is the predominant form of circulating folate and is responsible for performing many of the key metabolic functions of folate, including acting as a methyl group donor in the process of DNA methylation[8], which is fundamental to our overall wellbeing – especially as it pertains to cancer prevention, as proper methylation is required to protect the cells from mutations.

Folic acid requires a more complex metabolic process. It must first be converted to 5-MTHF in the liver or other tissues by an enzyme called dihydrofolate reductase (DHFR)[9]. This process is often slow, metabolically taxing, and inefficient in humans[10], potentially leading to unmetabolized folic acid circulating throughout the body[11].

While the long-term effects of unmetabolized folic acid are still under research, there are concerns about potential health implications. Some studies suggest that high levels of unmetabolized folic acid could disrupt natural folate metabolism[12], interfere with immune function[13], mask vitamin B12 deficiency[14], and increase the risk of certain cancers[15].

Turning Poison into Vitamins

Our bodies have evolved over thousands of years to efficiently absorb and utilize the nutrients locked in real food. While some synthetic supplements have their place, particularly for those with specific nutritional deficiencies, nutritional biochemistry indicates; their biochemical keys just don’t fit properly into our cellular locks. Think of nutrients found in nature as original keys that are made by a lock manufacturer (in this case our cells). These biological keys fit perfectly and always work as expected.

On the other hand, synthetic nutrients, made in a laboratory as opposed to a plant, are like poor copies of the original key. While they may still be able to fit in the lock, they don’t seem to work as smoothly and efficiently as the original. In other words, synthesised nutrients are not designed to replace the broad spectrum of nutrients found within real foods.

One more important example to share is Vitamin B12. Vitamin B12 deficiency is quite common these days[16] and can lead to a range of symptoms such as fatigue, weakness, constipation, loss of appetite, weight loss, and neurological changes. If left untreated, it can result in serious health issues including anemia and nervous system damage. Certain populations are at an increased risk for deficiency, such as older adults, those with gastrointestinal disorders, people who have undergone gastrointestinal surgery, vegetarians, vegans, and those with conditions affecting nutrient absorption such as pernicious anemia or celiac disease[17].

Even though individuals at risk for B12 deficiency should have their levels monitored closely, most supplement recommendations—and the variety most widely occurring in supplement form—are as far from natural as they come. Cyanocobalamin, is the most common form of vitamin B12, however most have no idea it is synthesised directly from a well recognized poison - in this case, cyanide[18]. Cyanocobalamin is synthesized in lab with the aid of cyanide and cobalt[19]. Even though cyanide is recognized as a poisonous substance, the amount used to create the synthetic version of B12 is extremely low and not exactly life threatening[20].

However, whether a “so-called” supplement will harm you or not, how many of us would consume it if we knew there were healthier food-derived forms of the same nutrient available? In case you’re wondering, the natural form of B12 found in food is known as methylcobalamin[21].

Nature Always works in Synergy

As alluded to at the beginning, in nature, nutrients often coexist in a state of synergy and do not seem to exhibit the same functionality once isolated[22]. To illustrate this, let’s look at vitamin E again, which naturally occurs in eight different forms (called isomers): four tocopherols (alpha, beta, gamma, and delta) and four tocotrienols (alpha, beta, gamma, and delta)[23]. When you provide the body with only one form, such as alpha-tocopherol, you run the risk of causing a cellular imbalance due to the absence of the other seven isomers[24]. Research seems to support the theory that the full family of vitamin E forms may be necessary for optimal health and that high intakes of only one form (i.e., alpha-tocopherol) may inhibit the absorption or function of the other vitamin E forms[25].

The same can be said for our other previous example, vitamin C. Vitamin C rarely, if ever, exists in isolation when found in a natural food source. Instead, it is often accompanied by a host of bioflavonoids, which are known for their ability to enhance the absorption and medicinal value of vitamin C[26]. Bioflavonoids, including rutin, quercetin, and hesperidin, have been found to improve the bioavailability of vitamin C and potentiate its antioxidant capacity[27]. So the research seems to affirm that  consuming nutrients like vitamin C in their isolated (and often synthetic) form might not be nearly as beneficial to the body, and may potentially cause imbalances, especially when compared to nutrients derived from a natural food matrix.

In conclusion, the synthetic derivation of supplements requires complex chemical manipulations, and are almost always found in isolated forms the body has great difficulty in recognizing and therefor using. Remember the principle: real food first, supplements second. Regularly consuming a diet rich in whole foods not only provides a complex matrix of nutrients but also beneficial compounds like fiber and phytochemicals that supplements may lack. If you do supplement, be aware of what you're consuming and choose forms closest to what nature intended, preferably coming directly from real organic fruits and vegetables.


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[3] Hoffer, A. (2012). "Orthomolecular Medicine for Physicians." Keats Publishing.
[4] Burton, G.W., et al. (1998). "Human plasma and tissue alpha-tocopherol concentrations in response to supplementation with deuterated natural and synthetic vitamin E." The American journal of clinical nutrition, 67(4):669-684.
[5] Carr, A.C., Pullar, J.M., Moran, S., & Vissers, M.C.M. (2012). "Bioavailability of vitamin C from kiwifruit in non-smoking males: determination of ‘healthy’ and ‘optimal’ intakes." Journal of Nutritional Science, 1:e14.
[6]  Kim, Y.I. (2007). "Folic acid supplementation and cancer risk: point." Cancer Epidemiology, Biomarkers & Prevention, 16(9):1893-1895.
[7] Wright, A.J., Dainty, J.R., & Finglas, P.M. (2007). "Folic acid metabolism in human subjects revisited: potential implications for proposed mandatory folic acid fortification in the UK." British Journal of Nutrition, 98(4):667-675.
[8] Stover, P.J. (2004). "Physiology of folate and vitamin B12 in health and disease." Nutrition Reviews, 62(6 Pt 2):S3-12; discussion S13.
[9] Obeid, R., Herrmann, W. (2012). "The emerging role of unmetabolized folic acid in human diseases: myth or reality?" Current Drug Metabolism, 13(8):1184-1195.
[10] Bailey, L.B., et al. (2015). "Biomarkers of Nutrition for Development—Folate Review." The Journal of Nutrition, 145(7):1636S-1680S.
[11] Kelly, P., McPartlin, J., Goggins, M., Weir, D. G., & Scott, J. M. (1997). "Unmetabolized folic acid in serum: acute studies in subjects consuming fortified food and supplements." The American Journal of Clinical Nutrition, 65(6):1790-1795.
[12] Obeid, R., Herrmann, W. (2012). "The emerging role of unmetabolized folic acid in human diseases: myth or reality?" Current Drug Metabolism, 13(8):1184-1195.
[13] Troen, A.M., et al. (2006). "Unmetabolized folic acid in plasma is associated with reduced natural killer cell cytotoxicity among postmenopausal women." The Journal of Nutrition, 136(1):189-194.
[14] Morris, M.S., Jacques, P.F., Rosenberg, I.H., & Selhub, J. (2007). "Folate and vitamin B-12 status in relation to anemia, macrocytosis, and cognitive impairment in older Americans in the age of folic acid fortification." The American Journal of Clinical Nutrition, 85(1):193-200.
[15]  Kim, Y.I. (2007). "Folic acid supplementation and cancer risk: point." Cancer Epidemiology, Biomarkers & Prevention, 16(9):1893-1895.
[16] National Institutes of Health. (2021). "Vitamin B12." Office of Dietary Supplements - Vitamin B12.
[17] Pawlak, R., Parrott, S. J., Raj, S., Cullum-Dugan, D., & Lucus, D. (2013). "How prevalent is vitamin B(12) deficiency among vegetarians?" Nutrition Reviews, 71(2), 110–117.
[18] Chanarin, I. (1979). "The cobalamins." Clinics in Haematology, 8(3), 657–680.
[19] Scott, J.M. (1999). "Bioavailability of vitamin B12." European Journal of Clinical Nutrition, 53(S1):S66-S69.
[20] Food and Nutrition Board, Institute of Medicine. (1998). "Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline." Washington, DC: National Academy Press.
[21] Paul, C., & Brady, D.M. (2017). "Comparative Bioavailability and Utilization of Particular Forms of B12 Supplements With Potential to Mitigate B12-related Genetic Polymorphisms." Integrative Medicine, 16(1):42-49.
[22] Jacobs, D. R., & Tapsell, L. C. (2007). "Food, not nutrients, is the fundamental unit in nutrition." Nutrition Reviews, 65(10):439-450.
[23] Shahidi, F., & De Camargo, A. C. (2016). "Tocopherols and Tocotrienols in Common and Emerging Dietary Sources: Occurrence, Applications, and Health Benefits." International Journal of Molecular Sciences, 17(10):1745.
[24] Traber, M.G., & Atkinson, J. (2007). "Vitamin E, antioxidant and nothing more." Free Radical Biology and Medicine, 43(1):4-15.
[25] Jiang, Q. (2014). "Natural forms of vitamin E: metabolism, antioxidant, and anti-inflammatory activities and their role in disease prevention and therapy." Free Radical Biology and Medicine, 72:76-90.
[26] Carr, A. C., & Maggini, S. (2017). "Vitamin C and Immune Function." Nutrients, 9(11):1211.
[27] Parhiz, H., Roohbakhsh, A., Soltani, F., Rezaee, R., & Iranshahi, M. (2015). "Antioxidant and anti-inflammatory properties of the citrus flavonoids hesperidin and hesperetin: an updated review of their molecular mechanisms and experimental models." Phytotherapy Research, 29(3):323-331.

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