Flaxseed lignans themselves have none of the positive health effects with which they are associated. Rather, they must first be broken down (metabolized) into their biologically active metabolites. These are known as enterolignans, of which there are two--enterodiol (ED) and enterolactone (EL). The human body itself cannot carry out this metabolism. Instead it must rely on friendly bacteria in the human or animal gut (called probiotics) to do so. (Estimates
vary on the exact ratio, but all estimates agree that there are more bacteria and other non-human cells than human cells in all of us!)
Unfortunately, not every human and animal gut has the right probiotics in it to carry out each of the stages this metabolism effectively and efficiently. Getting from raw flax to the desired enterolignans is a five (5)-step process. The first step in the process is mechanical. Research shows that crushing and milling flaxseeds is key to obtaining the maximum amount of secoisolariciresinol disglucoside (SDG), the key ingredient in our flax-based lignan products, from the flax seeds. (Kuijsten, 2005
). We take care of this step for you, as all of our flax products contain crushed, milled flax seed and all of our SDG extract products bypass this step altogether (but the trade off is loss of fiber and flax oil).
The other 4 steps, however, are performed by gut bacteria (primarily in the first and middle parts of the colon):
1. The SDG is first converted into secoisolariciresinol (SECO). This is nothing more than the removal of sugar (DG or diglucoside) molecules. The healthy gut will have several bacteria in it that are eager to carry out this step. (It turns out bacteria like sugar as much as the rest of us!)
2. Then SECO is converted into an intermediate molecule by the removal of one of more methyl groups (CH3). Apparently, methyl groups are less palatable than sugar as fewer bacteria species are capable of carrying out this step.
3. That intermediate molecule is then transformed into ED by the removal of one or more hydroxy groups (dehydroxylation). Again, a smaller group of bacteria (different from the bacteria involved in the prior step) are capable of carrying out this step. The good news is that ED is biologically active and can perform enterolactone duties even if no further metabolism takes place. In fact, even in the presence of the right gut bacteria, not all ED will be metabolized into EL, and that is actually preferable as it results in a blend of the two enterolactones.
4. Finally, some of the ED will be metabolized into EL by the removal of hydrogen from the ED molecules. This is carried out by a very small subset of bacteria species.
(Woting et al, 2010
, 507.) Thus, gut microbes are absolutely critical to the production of EN and EL. In fact, there would be no EN or EL production at all without those microbes. Accordingly, getting the right mix and quantity of gut microbes should improve the effectiveness of any lignans-based therapy.
The more SDG by-products that are produced at each stage, the more ED and EL that will ultimately be produced. (Clavel, 2005
at 6080, 6082.) Accordingly, probiotics that promote the bacteria used in each stage should maximize total ED and EL production.
Although less research has been done with HMR and some of the other lignans, all of them require metabolism by microbes in a process similar to that described above for flax-based lignans. (Note that HMR is not a precursor to ED but only for the EL enterolignan.)
In developing our probiotic, we have taken the latest research (much of which is cited in the links above) into account in light of commercially available bacteria strains to produce a enterolactone-friendly probiotic. In addition, those bacteria themselves need to be fed in order to promote their growth and activity. Accordingly, we have added the pre-biotic inulin to our blend. (As an additional benefit, there are hints in the research that the addition of inulin to probiotics prevents a plateau effect that has frequently been observed in enterolactone production. Contrast Stumpf, et al. (2000)
with Tarpila et al. (2002)
, for example.)
Wang, Meselhy, Li, Qin, Hattori, Human Intestinal Bacteria Capable of Transforming Seciosolariciresinol Diglucoside to Mammalian Lignans, Enterodiol and Enterolactone
, Chem. Pharm. Bull. 48(11), 1609 (2000).
Clavel, T., Doré, J., & Blaut, M. (2006). Bioavailability of lignans in human subjects. Nutrition Research Reviews
, 19(2), 187-196. doi:10.1017/S0954422407249704
Bravo, D., Peirotén, A., Álvarez, I., Landete, J., Phytoestrogen metabolism by lactic acid bacteria: Enterolignan production by Lactobacillus salivarius and Lactobacillus gasseri strains
Journal of Functional Foods 37 (2017) 373-378. https://www.sciencedirect.com/science/article/pii/S1756464617304796
Gaya, P., Peirotén, A., Medina, M., Landete, J., Bifidobacterium adolescentis INIA P784: The first probiotic bacterium capable of producing enterodiol from lignan extracts
, Journal of Functional Foods 29 (2017) 269-74. https://www.sciencedirect.com/science/article/pii/S1756464616304431?via%3Dihub
Peiroténa, A., Gayaa, P., Álvarezb, I., Bravoa, D., Landetea, J., Influence of different lignan compounds on enterolignan production by Bifidobacterium and Lactobacillus strains
, Int. J. Food Microbiology 289 (2019) 17-23. https://www.ncbi.nlm.nih.gov/pubmed/30193121