Not all B-vitamins are created equally. Ours are activated (not like nuts).
Activated vitamins are vitamins in their most active form, meaning that they are more bioavailable for immediate absorption into your system. When vitamins are taken in their inactive form, they have to be activated by the liver and/or kidneys before the body can absorb and utilize them. (1) Consuming the active form essentially skips this step, particularly important for anyone with liver or kidney issues, but also in the case of a multitude of other conditions requiring more immediate bioavailability or increased safety levels. (1)
Certain genetic defects, or low dietary consumption of specific vitamins, can lead to deficiencies due to low absorption rate. These vitamin deficiencies can lead to a vast array of negative effects on the body; from reduced immune system, to metabolic disruption, or cognitive dysfunction. It is therefore critical to ensure that you are achieving the recommended daily intake for favourable health outcomes. For some people, taking a supplement is recommended, especially if optimal intake is not being achieved through diet, or if there are underlying medical conditions that may effect absorption.
Table 1 - Vitamins and their active forms (2)
Some Comparisons Between Inactive and Active Vitamin Supplements
Vitamin B6 versus Pyridoxal 5’ Phosphate (P5P)
Vitamin B6 is naturally occurring in many fruits, vegetables and grains in the less bioavailable glycosylated form. (3) In order to get the most out of this less bioavailable version, the liver must first convert it to P5P, which is the most biologically active form of vitamin B6. (4) This active form, P5P, acts as a cofactor for more than 150 enzymes in the body, particularly in protein metabolism, and transsulfuration and decarboxylation reactions. (3, 5)
Vitamin B6 deficiency has been associated with neurological disorders and anaemia, whereas adequate levels are associated with a decrease of inflammation in the body. (4, 6)
Full liver and intestinal function is necessary to successfully convert vitamin B6 to its active form, P5P. In circumstances where there may be problems with the conversion from inactive vitamin B6 to P5P, for example, where there is reduced liver function, it can be beneficial to supplement directly with P5P (active form) to ensure maximum absorption. (7) Difficulties in the conversion by the liver into P5P have been noted in people with diabetes mellitus, celiac disease, and chronic alcoholism. (4)
Folate versus 5-MTHF
Folate deficiency is associated with an increase in neural tube defects, cardiovascular disease, cancer, and cognitive dysfunction. (8) There are three common forms of folate supplementation; folic acid, folinic acid or 5-methyltetrahydrofolate (5-MTHF), with the two latter forms being the active versions.
Studies have shown that 5-MTHF may have numerous advantages over the synthetic folic acid, mainly because 5-MTHF is well-absorbed even when there are gastrointestinal disturbances or metabolic defects. (8) A study conducted by Servy et al. looked at 30 couples who had been having fertility problems for at least four years. (9) At least one person from each couple exhibited a MTHFR gene mutation, a relatively common genetic issue, and most of the women had been previously treated with the current standard recommendation of folic acid. (9) For this study, the couples were given 600 micrograms of 5-MTHF per day for 4 months. Thirteen of the couples conceived spontaneously in their first series of Assisted Reproductive Treatment (ART) post study, and only three couples had not fallen pregnant by the time of publication. (9) This study concludes that, although standard folic acid supplementation may be adequate for some, 5-MTHF offers a more appropriate option for those with MTHFR gene mutations as this will allow for appropriate levels of folate to be absorbed to help prevent negative outcomes. (9)
Using the active form of folate, MTHF-5, instead of folic acid, also has other known benefits, including:
- Reducing the potential for concealing haematological signs of vitamin B12 deficiency.
- Reducing interactions with drugs that inhibit dihydrofolate reductase.
- Preventing the potential negative effects of unconverted folic acid in the peripheral circulation. (8)
Cobalamin (Vitamin B12) versus Methylcobalamin (active form)
Similarly to the other examples, some studies have shown that using the active form of vitamin B12, methylcobalamin (MeCbl), is superior for its bioavailability and safety. (1) It has been shown that using cobalamin (CNCbl) results in reduced tissue retention of active vitamin B12, and that this may pose problems for those with particular nucleotide polymorphisms affecting their vitamin B12 metabolic pathways. (1) There are also concerns amongst researchers that long-term supplementation with CNCbl may result in a build-up of cyanide in human tissues. (1) For this reason, although MeCbl is typically more expensive, it is considered a superior form to CNCbl.
In conclusion, although many people may achieve adequate levels of individual vitamins through their diet or with the inactive versions of vitamin supplements, it is worth assessing vitamin status to ensure deficiencies are not overlooked. In the case of large deficiencies, certain genetic mutations, intestinal malabsorption, diabetes, alcoholism, or celiac disease, supplementation with the active forms would be the best choice due to superior bioavailability and safety levels.
1. Paul C, Brady DM. Comparative Bioavailability and Utilization of Particular Forms of B(12) Supplements With Potential to Mitigate B(12)-related Genetic Polymorphisms. Integr Med (Encinitas). 2017;16(1):42-9.
2. Amboss. Vitamins. 2020. Available from: https://next.amboss.com/us/article/Ao0ReS#Zd13394f3e11b9200dec7ab35fb04a2c2
4. Said HM. Intestinal absorption of water-soluble vitamins in health and disease. Biochem J. 2011;437(3):357-72.
5. Paiardini A, Giardina G, Rossignoli G, et al. New insights emerging from recent investigations on human group II pyridoxal 5’-phosphate decarboxylases. Curr Med Chem. 2017;24(3):226-44.
6. Ueland PM, McCann A, Midttun O, et al. Inflammation, vitamin B6 and related pathways. Mol Aspects Med 2017;53:10-27.
7. Labadarios D, Rossouw JE, McConnell JB, et al. Vitamin B6 deficiency in chronic liver disease--evidence for increased degradation of pyridoxal-5’-phosphate. Gut 1977;18(1):23-27.
8. Scaglione F, Panzavolta G. Folate, folic acid and 5-methyltetrahydrofolate are not the same thing. Xenobiotica. 2014;44(5):480-488. doi:10.3109/00498254.2013.845705
9. Servy EJ, Jacquesson-Fournols L, Cohen M, Menezo YJR. MTHFR isoform carriers. 5-MTHF (5-methyl tetrahydrofolate) vs folic acid: a key to pregnancy outcome: a case series. Journal of Assisted Reproduction and Genetics. 2018;35(8):1431-5.
Written By Brittany Darling
NUTRITIONIST (BHSC), WESTERN HERBAL MEDICINE (ADV DIP),
CERT. PAEDIATRIC NUTRITION