Human intestinal lining

It’s a mystery that has puzzled scientists for decades: Why do many natural compounds exert beneficial health effects when ingested by humans despite being minimally absorbed or not absorbed at all?

In other words, take, say, 100 mg of compound X and you poop 100 mg of compound X out in the toilet—there was no absorption. Yet some beneficial effect results such as reduction of an inflammatory blood marker or reduction in blood sugar. This paradox has fueled plenty of research and commercial efforts to discover ways to increase absorption.

Just look at the hype surrounding curcumin. Curcumin is an example I’ve discussed previously  that illustrates how something that is minimally absorbed can still exert beneficial health effects. Swallow 100 mg of curcumin and you pass 99 mg or more into the toilet—there is little to no absorption. But you can measure a reduction in C-reactive protein, IL-2 and other interleukins, TNF-alpha and other inflammatory markers in the blood. Many people experience a reduction in knee pain and swelling from osteoarthritis or rheumatoid arthritis with curcumin. Psoriasis and a number of other skin rashes can improve. There is reduced progression of pre-diabetes to type 2 diabetes—real measurable effects develop with curcumin ingestion despite very little gaining access into the bloodstream and body organs. Its poor absorbability has prompted efforts to increase curcumin’s absorption by adding ingredients such as piperine or bioperine, or deliver it as a nanoparticle or liposomal preparation.

But we also know that curcumin is an antifungal agent effective against many species of fungi such as Candida albicans. It also exerts antibacterial properties against pathogenic or undesirable intestinal bacterial species. Curcumin has also been shown to strengthen the intestinal cellular and mucus barriers, thereby reducing endotoxemia. In other words, we do not necessarily want absorption of curcumin because its primary site of action is within the intestine. Recall that undesirable microbial species that populate the gastrointestinal (GI) tract, especially when inhabiting the full 30-foot length of colon, ileum, jejunum, and duodenum, release components of their cell walls, some of which gains access into the bloodstream, a process labeled endotoxemia. The phenomenon of endotoxemia explains how microbes in the GI tract can be experienced as a skin rash like rosacea, a brain condition such as multiple sclerosis or Parkinson’s disease, or joint pain in the low back or knee, body parts far away from the GI tract. What if some new version of curcumin were 100% absorbed—would we actually lose many of its benefits? I think we would.

What other potentially beneficial natural compounds share this failure to be absorbed yet have been shown to exert beneficial effects? The list is long but includes:

  • Green tea catechins—such as epigallocatechin. Green tea catechins provide weight loss benefits, as well as anti-cancer and anti-inflammatory effects. Green tea catechins also influence the composition of species in the intestinal microbiome and crosslink the mucin proteins in the intestinal mucus barrier, converting the semiliquid mucus into a gel, a more effective barrier against endotoxemia.
  • Eugenol—The essential oil from cloves and cinnamon has anti-inflammatory and antioxidant properties. It also has stimulatory effects on beneficial Clostridia species in the GI tract that, in turn, help strengthen the intestinal mucus barrier.
  • Resveratrol—Resveratrol sourced from grapes, cranberries, and wine exerts anticancer and anti-inflammatory effects. Resveratrol influences the composition of microbial species in the GI tract such as increasing Lactobacillus species and Akkermansia.
  • Anthocyanins—These are the flavonoids from blue-, purple-, and red-colored fruits such as blueberries, blackberries, and cranberries that increase Bifidobacteria and Lactobacillus species while reducing endotoxemia. They have been associated with reduced risk for cardiovascular disease, some forms of cancer, neurodegenerative disorders, and aging-associated bone loss despite minimal absorption.

We’re talking about hundreds, even thousands, of food components that, despite poor absorption into the bloodstream, nonetheless exert positive health benefits.

Do we really want absorption of these compounds into the bloodstream to occur? Or should we simply conclude that these compounds exert their benefits on human health via some microbe-mediated process, whether a shift in microbial species composition, microbial metabolism to modified forms, or an effect on the intestinal barrier and reduction in endotoxemia? I believe that we should be less concerned with increasing absorption of these many natural factors and focus more on understanding what change in the microbiome or intestinal barrier mediates such beneficial effects. In other words, we should be less focused on understanding, for example, how anthocyanins exert effects on oxidized LDL particles or inflammatory mediators and more focused on how bowel flora act as an intermediary for such effects.

Are you coming to appreciate that so many things—nutrients, nutritional supplements, pharmaceuticals, food—all need to be re-examined through the lens of the microbiome?