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Bioactive Forms of Nutrients: Not all Supplements Are Created Equal

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A sure fire way to assess the quality of your supplements is to check if the vitamins and mineral are in the most biologically active and absorbable forms. Most formulations contain vitamins and minerals in their most commonly used and often cheapest form. To the untrained eye this may not seem like a big deal especially if the cost of the formulation seems like a good bargain. Allow me to shed some light on why the most active forms of vitamins and minerals can have a substantial benefit to your health and can sometimes be the difference between on effect vs. a profound shift in your health.


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The body’s physiology is intricate and complex and it often converts orally absorbed nutrients a number of times before it is in a form that is useable. A good example is the amino acid tryptophan. It has been traditionally used as precursor to the neurotransmitter serotonin however it first must be converted to 5- hydroxytrytphan (5-HTP) before serotonin is formed. It is advantageous to supplement with 5-HTP since it is a step closer to the desired molecule.

In other cases certain forms of vitamins are absorbed better in our digestive tracts than others. A good example is calcium. The most commonly used form of calcium is calcium carbonate (minerals are supplemented as combination compounds called salts or chelates to maintain stability). Its absorbability is similar to calcium citrate but it requires an acidic environment to be optimally absorbed so it must be taken with meals. Furthermore, acid reducing medications (PPI’s) reduce its absorption since they reduce stomach acidity (PPIs used for more than 12 months cause a magnesium deficiency). Calcium citrate does not require an acidic environment to be absorbed so a higher percentage of absorption can be achieved in people with low stomach acid (which is actually quite common).

Another great example is a form of B1 (thiamin) called benfotiamine. B1 is essential in preventing the damaging effects of high blood sugar in diabetics. Many studies have shown it has a powerful effect on reducing nerve pain and damage to sensitive tissues such as the capillaries in the retina. Although benfotiamine is not lipid soluble, it has been shown to have very good bioavailability. This is because benfotiamine is converted into a more fat-soluble compound by enzymes present in the cells of the intestinal mucosa. This allows it to pass easily through cell membranes and become absorbed. Once absorbed it travels back to the liver where it is converted to thiamine and released into the bloodstream. This means that benfotiamine is better absorbed than thiamin itself. Thiamin absorption from benfotiamine has been shown to be about five times as great as from conventional thiamin supplements (1).

Certain vitamins require specific enzymes to convert them into the active forms within the body. Two classic examples are vitamin B6 and folic acid. Vitamin B6 (Pyridoxine) is absorbed in the intestines and converted to its active form, pyridoxal-5′-phosphate, in the liver by the enzyme AOR04173-P5P-lge-200x330pyridoxal kinase. However, in some people their liver function is slow or impaired so the production of P5P will be limited. One study found that in patients with impaired liver function, only 33% responded to pyridoxine hydrochloride supplementation with an increase in plasma P5P, where as all of the patients receiving P5P supplementation experienced an increase (2). P5P is beneficial for the treatment of depression since it is an essential cofactor for neurotransmitter production, improve carpal tunnel syndrome and it can reduce the harmful amino acid homocystine, which can impair the production of glutathione and predispose a person to multiple health conditions including Alzheimer’s disease, sudden cardiac events and many more.

Folic acid is essential for DNA and RNA formation, genomic maintenance, and red blood cell production. A deficiency during pregnancy was found to cause neural tube defects in infants so it was mandated by governmental agencies that folic acid should be fortified in standard foods such as bread and cereals. Natural folates are found in dark green leafy vegetables (spinach, kale, mustard greens, turnip greens) and other vegetables and their absorption is approximately 50% less than that of supplemental folic acid.

Even though folic acid has good intestinal absorption its conversion is to its active form, 5-Methyltetrahydrofolate (5-MTHF) hinges on the enzyme methylenetetrahydrofolate reductase. The family of genes that are responsible for the production of this enzyme are often malfunctioning in a large proportion of the population especially those that are chronically ill or have neurodevelopmental disorders (such as autism). The figures are not exact but experts and studies both report that anywhere between 50-75% of the population have at least one or two mutations of the MTHF genes. This means that these people have a sluggish or impaired formation of 5-MTHF, which plays a key role in cell and DNA repair, detoxification, homocystine metabolism, and cancer prevention. This predisposes these people to cardiovascular disease, autoimmune disorders, mental and neurophysciatric illness such as bipolar and schizophrenia and neurodevelopmental disorders such as autism.

Supplementing with the 5-MTHF form of folic acid can bypass the impaired genes and enzyme and carry out the essential functions. As a note, folic acid (or 5-MTHF) should be supplemented with vitamin B12 since they work in together in the stimulating neurological pathways and homocystine detoxification, and folic acid supplementation can hide the symptoms of B12 deficiency.

Hopefully you have gained an appreciation of how supplementing with the most biologically active forms of certain vitamins not only provide superior action and health benefits but also end up providing better value for your dollar since the dose is usually smaller and absorptions is better. Clearly, not all supplements have been created equal since there are many products that still use poorly absorbed forms. So if you want superior benefits from your supplements look for products that use active forms and don’t cut corners on your health.

  1. Loew D. Int J Clin Pharmacol Ther. 1996 Feb;34(2):47-50. Pharmacokinetics of thiamine derivatives especially of benfotiamine.
  2. Labadarios D, Rossouw JE, McConnell JB, Davis M, Williams R. Gut. 1977 Jan;18(1):23-7. Vitamin B6 deficiency in chronic liver disease–evidence for increased degradation of pyridoxal-5′-phosphate.


  1. Michelle Park Reply

    Great Blog! Very Informative Dr. Hrkal!

    1. Dr Paul Hrkal Reply

      Thanks Michelle

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