Does search for single component active constituents throw baby out with bath water?

By Hank Schultz contact

- Last updated on GMT

Image © iStockPhoto / PushishDonhongsa
Image © iStockPhoto / PushishDonhongsa

Related tags: Clinical trial

Pharmaceutical-style reductionism has been the order of the day in the dietary supplement business. But strong synergistic countercurrents still exist, generated by product developers adhering to older traditions such as TCM and Ayurveda.

After the inception of DSHEA, investment flooded into the field, much of it from the drug company end of the spectrum. Researchers and product developers started focusing on herbs from a standpoint of identifying, deriving and concentrating their active constituents, and then embarking on a course of trying to pin down their modes of action, zeroing in on dosage levels, boosting bioavailability of these often hard-to-absorb molecules and so forth. Some industry stakeholders who come from the traditional herbalist side of the industry wonder if this is a case of throwing the baby out with the bathwater.

Active constituents

Consider the concept of active constituents. David Winston, president of Herbalist & Alchemist, a traditional herbal product manufacturing company, says that the notion that it is known in many cases which specific chemicals in herbs account for their activity in the body, and how those chemicals are having these effects, is a fantasy for the most part.

“The dietary supplement world has basically bought this hook, line and sinker,”​ Winston told NutraIngredients-USA. “The reality is that we have not nailed down the mode of action for most herbs.

“Yes, this might be true if you are talking about ginkgo. There are others like yohimbe, which I’m not really fond of, but in that case yohimbine has been identified as the active constituent. But for the vast amount of herbs we do not know what the active constituent is. Most of the standardized extracts are standardized to a marker compound, which works for identity but says nothing about efficacy,”​ he said.

Winston gave as an example the herb hawthorn (Crataegus monogyna​), noted for its beneficial effects on the cardiovascular system. Extracting a single polyphenol from this plant proved to be a failure in a clinical trial. The message from that trial was clear, he said: “The active constituent of hawthorn is hawthorn itself.”

Evidence based?

The pharmaceutical model has the advantage of being somewhat more easily fitted into the scientific method in which paring down variables is part of successful clinical trial design. Some observers have seen this as a good thing for the industry, helping it to more easily make its case for efficacy and quality manufacturing with regulators and the press.

Botanical capsules © darios44
Image © iStockPhoto / darios44

“I’m not sure the term ‘reductionism’ is totally accurate,”​ said Mark Blumenthal, founder and executive director of the American Botanical Council. “I would perhaps substitute the term ‘evidence-based’ as defined by evidence from clinical trials as opposed to information from traditional uses such as in Ayurveda, TCM or other traditions based on a theory of energetics.”

For Winston, the effort to provide ‘evidence’ for the activity of herbs through clinical trials is often misguided. The message that ‘we’re like drugs, only not as powerfully acting and without their side effects’ misses the point, in his opinion.  Winston uses a concept borrowed from toxicology—hormesis—to help illustrate the difference. Hormesis is defined by one NIH researcher as “a biphasic dose response to an environmental agent characterized by a low dose stimulation or beneficial effect and a high dose inhibitory or toxic effect.”

“The idea of hormesis is if you administer a pharmaceutical (or a supplement you tried to model after a pharmaceutical) you have a receptor in the body you are trying to hit and and you are trying to hit that receptor with everything you’ve got.  It’s like the old carnival attraction where you hit the target with a hammer and if you hit it hard enough the weight flies up and rings the bell. Herbs just don’t work that way,” ​Winston said.

Herbs in concert

Winston said that traditional systems like TCM and Ayurveda have hundreds of years of evidence in the form of texts and the experience of thousands of practitioners to draw upon, and just because this is not presented in the form of the Western scientific method with abstract, hypothesis, trial design, results and conclusion should not lessen its validity. In recent years, Chinese researchers have conducted hundreds of clinical trials on TCM formulas.  These trials are more in line with those typically done in the West but still with important differences, including some end points that don’t often make perfect sense to Western observers, Winston said. (And the language barrier is considerable.) In Japan, where TCM formulas have been standardized under the Kampo tradition of medicine, trials on these formulas more closely approximate the Western model, he added.

But even as these traditional systems move more toward providing the kind of information that qualifies as ‘evidence’ in the West, they still rest upon a fundamentally different foundation, Winston said. Synergy for these practitioners is not just a marketing concept, but a foundational principle.

“With herbs (as opposed to drugs, or supplements modeled on them) it is a little bit like the bizarre sport called curling. One guy lets go of the stone and you’ve got other guys sweeping out front, or to the side trying to get the stone to move in a certain way. In these formulas, one compound is pushing a little bit here and others are pushing a little bit there and overall you get a significant response. But you are not trying to just hit one receptor or shut a specific one off. That’s why in every traditional medicine system in the world herbs are never used as single ingredients. They are always used in concert,”​ he said.

“As for synergy, I believe in it and I’ve seen it work. If you asked me 15 years ago if I could prove it I would have had to say no. But a lot of work has been done in the intervening years showing that if you combine herbs you get better activity,”​ Winston said.

Blumenthal said he believes there will always be a place for both approaches in the market.

“You see product development happening on both ends. You do see products in the market that follow historical uses in Ayurveda or TCM were herbs follow the traditional formulas or variations thereof and the skeleton of that formula might go back to something that was published hundreds of years ago and developed since then,”​ he said.

Underbelly of multi-ingredient formulas

But he draws a distinction between multi-ingredient formulas based upon these traditional models and those that seem to have been drawn up from lists of available ingredients from suppliers, i.e., two from column A, five from column B and so forth. Some helper or adjuvant herbs in a TCM formula might be present in only minute quantity, but they have a specific role and the ratios between herbs in the formula has some basis in either trials or from clinical practice. Then there is the Western model of pixie dusting, Blumenthal said.

“You might have a lot of ingredients that have traditional uses for a certain indication. But if you just put them all into a bottle, how do you really look your customer straight in the eye and tell them that this new, unique formula is really going to do what you claim it will do?”​ Blumenthal said.

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1 comment

Herbal/Natural Products should not be treated as drugs

Posted by Olajuwon Okubena,

Some herbal and natural products contain macro/micro nutrients which provide health benefits. Isolating active compounds in such products and developing them into drugs would only address a small fraction of what the totality of the product would address. To illustrate, there is a Sorghum bicolor based food supplement which contain almost all the essential macro/micro nutrients such as omega3,6 & 9, selenium, calcium, phosphorus, manganese, iron, vitamins dietary fibre. Clinical studies confirm that the whole product has antioxidant, antiinflammatory and immune modulating properties. Through bio-assay guided fractionation, the active ingredient was identified and it is less than .05% of the total weight. It was discovered to be active as anti-inflammatory agent. Concentrating on the development of this active would ignore the major part of the product which contains useful macro/micro ingredients.

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