Herbalists, though we’ve been known to use isolated constituents from plants, often prefer traditional, whole-plant preparations like teas, tinctures, or powders. These “crude” extracts, we often claim, may appear to be less concentrated but are actually more effective than isolated molecules when given by mouth to a living, breathing human being. But is there any evidence to support this claim? If a certain constituent has therapeutic activity, it seems counterintuitive that refining and concentrating it might somehow make it less effective.
The issue, in the end, is one of bioavailability: the ability of medicinal chemicals to reach the target areas in the human body where they can exert their effects. It does us little good to take high doses of molecules that never reach tissue at appreciable concentrations. This, of course, is one of the problems with petri dish research: a given chemical may have an effect on neurons in a lab, but that’s far from a guarantee that it will enter our bloodstream, leave the liver unchanged, cross our blood-brain-barrier, and have the same effects on neurons in our central nervous system.
One of the most famous, and researched, examples comes to us from the traditional Indian spice turmeric (ground rhizome of Curcuma longa). Curcumin and its molecular relatives the curcuminoids are polyphenolic pungent chemicals found in turmeric. They have attracted substantial attention, especially over the last decade, as potential medicinal compounds. But as a recent review article discovered,1 this rarely translates to clinically-relevant benefit. The article’s authors explored a range of reasons, but two stick out: first, curcumin is very difficult to absorb, with only small fractions of an oral dose making it into the bloodstream. But second (and perhaps more crucially), curcumin is often altered and/or destroyed by the body’s digestive and metabolic function before it even gets a chance to be absorbed. No wonder researchers don’t find it in the blood even after oral administration of 1,000mg of pure curcumin!
This vexing issue has dogged researchers attempting to harness any potential power in turmeric. Curcumin has been wrapped in special “nanoparticles,” blended with pungent alkaloids from black pepper, and mixed with essential oils found in whole turmeric. All these preparations show some advantages over pure curcumin, but not by much. What seems to really make a difference is to mix curcuminoids with fiber (including cellulose) and other polyphenols (including flavonoids). Given by mouth, these preparations increased the concentrations of curcuminoids in blood over 300-fold compared to isolated curcumin – even though the amount of curcumin in the mixture was about 6 times lower than the amount given in isolated form.2
The reason this particular formulation works is most likely because the fiber matrix and the presence of additional polyphenolic compounds alter the metabolism of curcuminoids, protecting them from degradation and allowing them to enter the bloodstream unaltered. This is why, even at relatively low doses (2-3 grams a day), whole turmeric powder has relevant clinical effects even though the amount of curcuminoids it contains is much, much lower than what’s found in concentrated extracts (75mg in 3g of turmeric, vs. 1,000mg or more in an extract).3 The matrix alters the way our body interacts with the chemicals – sparing them from metabolism so they can actually work! This is great news because whole turmeric powder isn’t just a better way to get high plasma levels of curcuminoids: it’s also a tastier and much more affordable option. This makes sense: we didn’t get interested in studying turmeric because of curcuminoids, we got interested by observing thousands of years of whole-plant traditional use. That’s what informed our understanding of its medicinal value. It’s not surprising that traditional preparation methods maximize its effectiveness. This may not be true for all plants, but it certainly seems to be for turmeric – especially now that we’re finding even curcumin-free turmeric preparations seem to have interesting medicinal activity.4
Let’s look at another example. Quercetin is a bioflavonoid, sourced from plants, that has received attention for a range of potential applications.5 Excited about its prospects, marketers have developed products spiked with this molecule that purport to provide increased energy and concentration, and balance inflammation in the body.6 Clinical trials with this isolated compound, however, yield mixed results and often fail to show consistent effects: whether for high cholesterol,7 prostate cancer,8 blood pressure,9 or inflammatory bowel disease,10 quercetin doesn’t always live up to its promise. The researchers reviewing its potential for prostate cancer noted that bioavailability, just as with curcumin, is the major stumbling block. The researchers reviewing its effects on blood pressure noted that large doses, higher than 500mg of quercetin per day, were needed to achieve modest clinical effects (by way of reference, an apple contains around 10-15mg of quercetin).11
Recently, researchers have continued to explore the therapeutic potential of quercetin in inflammatory bowel disease (for example, Crohn’s disease or ulcerative colitis), but with a twist: this time they’re taking a look at a cousin molecule to quercetin, known as rutin.12 Rutin is almost identical to quercetin, except that it has two sugar molecules (glucose and rhamnose) stuck to it. It turns out that this is usually the way we find quercetin in plants – as rutin, which is known as a glycoside of quercetin because of the sugar molecules stuck to it, or as another glycoside of quercetin known as quercitrin with only one sugar attached to it. Almost all of an apple’s content of “quercetin” is actually in the form of rutin and quercitrin.13 Other plants, like goldenrod, contain much higher quantities of rutin and quercitrin14 and have been used medicinally for a really long time.
Why have these glycosides of quercetin received so much recent attention? One reason is that they may be the best ways of delivering quercetin itself into the bloodstream. Pre-clinical research has found this to be the case, specifically in models of inflammatory bowel disease: rutin helps, but quercetin doesn’t.15 This led researchers to speculate, in the most recent review, that rutin might act as a “prodrug that delivers the bioactive quercetin dose.”16 The sugars stuck to the molecule protect it from degradation as it moves through our GI tract, just as fiber and associated polyphenols help curcumin reach our bloodstream intact. A whole plant, like goldenrod, might be the best way to deliver quercetin to the body. Isolating the molecule from the plant might make it much less effective.
Herbalists have known about this for a long time. Perhaps the clearest description of the hazards that await “unprotected” polyphenols in our gut, and how whole plants act to preserve them intact, is found in Simon Mills’ and Kerry Bone’s work Principles and Practices of Phytotherapy (2nd edition).17 And again, herbs teach us a valuable lesson: we need to approach their molecular constituents not as potential drugs that need to be isolated and refined. Plants are complex chemistry-delivering living beings whose interface with our physiology relies on cultural wisdom for optimal function. This isn’t to say that we can’t find useful, isolated molecules from plants: this approach worked well (for the most part) with strong constituents like alkaloids (morphine, cocaine, atropine), but this seems to be the exception rather than the rule. Perhaps, before dismissing constituents like curcumin or quercetin, we should give them a chance to work as evolution intended: dancing with us as part of a rich, diverse, seasonally-fluctuating stream of phytochemistry. If you’re curious to know how one might do this, you’re in luck: the art and science of herbal medicine has mapped a lot of it out for us – from golden milk to goldenrod tea. And it’s all pretty tasty, unlike most pills.
1. Nelson, Kathryn M., et al. “The Essential Medicinal Chemistry of Curcumin: Miniperspective.” Journal of Medicinal Chemistry (2017)
2. Jäger, Ralf, et al. “Comparative absorption of curcumin formulations.” Nutrition journal 13.1 (2014): 11.
3. Amin, F., et al. “Clinical efficacy of the co-administration of Turmeric and Black seeds (Kalongi) in metabolic syndrome–A double blind randomized controlled trial–TAK-MetS trial.” Complementary therapies in medicine 23.2 (2015): 165-174.
4. Aggarwal, Bharat B., et al. “Curcumin‐free turmeric exhibits anti‐inflammatory and anticancer activities: Identification of novel components of turmeric.” Molecular nutrition & food research 57.9 (2013): 1529-1542.
5. Alrawaiq, Nadia Salem, and Azman Abdullah. “A review of flavonoid quercetin: metabolism, bioactivity and antioxidant properties.” International Journal of PharmTech Research 6.3 (2014): 933-941.
7. Sahebkar, Amirhossein. “Effects of quercetin supplementation on lipid profile: A systematic review and meta-analysis of randomized controlled trials.” Critical reviews in food science and nutrition 57.4 (2017): 666-676.
8. Yang, Feiya, et al. “Quercetin in prostate cancer: Chemotherapeutic and chemopreventive effects, mechanisms and clinical application potential (Review).” Oncology reports 33.6 (2015): 2659-2668.
9. Serban, Maria‐Corina, et al. “Effects of Quercetin on Blood Pressure: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials.” Journal of the American Heart Association 5.7 (2016): e002713.
10. H Farzaei, Mohammad, Roja Rahimi, and Mohammad Abdollahi. “The role of dietary polyphenols in the management of inflammatory bowel disease.” Current pharmaceutical biotechnology 16.3 (2015):
11. Bhagwat, Seema, David B. Haytowitz, and Joanne M. Holden. “USDA database for the flavonoid content of selected foods, Release 3.1.” US Department of Agriculture: Beltsville, MD, USA (2014).
12.Habtemariam, S., and A. Belai. “Natural Therapies of the Inflammatory Bowel Disease: The Case of Rutin and its Aglycone, Quercetin.” Mini reviews in medicinal chemistry (2017).
13. Liaudanskas, Mindaugas, et al. “A comparative study of phenolic content in apple fruits.” International Journal of Food Properties 18.5 (2015): 945-953.
14. Radusiene, Jolita, et al. “Assessment of phenolic compound accumulation in two widespread goldenrods.” Industrial Crops and Products 63 (2015): 158-166.
15. Kwon, Ki Han, et al. “Dietary rutin, but not its aglycone quercetin, ameliorates dextran sulfate sodium-induced experimental colitis in mice: attenuation of pro-inflammatory gene expression.” Biochemical pharmacology 69.3 (2005): 395-406.
16. Habtemariam, S., and A. Belai. “Natural Therapies of the Inflammatory Bowel Disease: The Case of Rutin and its Aglycone, Quercetin.” Mini reviews in medicinal chemistry (2017).
17. Bone, Kerry, and Simon Mills. Principles and practice of phytotherapy: modern herbal medicine. Elsevier Health Sciences, 2013. Page 63
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