Elephant in Room: Is ‘synergy’ in supplements just hype? It’s complicated

Synergy is a term often employed in the marketing of multi-ingredient dietary supplements. Is such a claim supportable? Or is it just marketing hype? It is, well, complicated. 

Synergy is generally defined as the interaction of two or more agents to produce a combined effect greater than the sum of their individual effects. 

In the research of medicinal herbs and other supplement ingredients, this can be subdivided based on the mode of action. Either these constituents exhibit pharmacodynamic synergy (enhanced therapeutic actions on the same target) or pharmacokinetic synergy (no direct interaction but with multi-target behavior). 

Synergy is foundational idea in traditional herbal medicine 

Synergistic effects have long been a mainstay of traditional medicinal systems, such as Traditional Chinese Medicine (TCM) and Ayurveda. But translating those ideas into the modern production of standardized extracts and ingredients enhanced for better absorption is a challenge. 

In traditional systems, such as TCM, formulas were assembled by individual practitioners generally from whole herb sources. Thus, while there was no “standardization” per se, the herbs that went into each formula and amount of each constituent used was generally uniform. 

According to a recent review, “The concept of synergy is an intrinsic part of TCM philosophy and is often described in a more holistic way. The complex synergistic interactions among the herbs in complex Chinese Herbal Medicine (CHM) formulations are believed to be able to enhance the bioavailability of active components, promote therapeutic effects and/or reduce toxicity.” 

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The authors noted TCM formulas are often assembled using a framework known as “Jun-Chen-Zuo-Shi” (also known as “Emperor–Minister-Assistant-Courier”) in which each herb has a specific ratio and purpose, either to reach a target receptor in the body, assist in bioavailability or minimize toxicity or undesirable side effects. 

But a research framework to verify these synergistic effects still falls short of the mark, according to the authors. 

“The currently available methods have various significant limitations on the synergy studies of Chinese Herbal Medicine (CHM); more methodological development is urgently needed in the future,” they wrote. “Despite synergistic effects demonstrated in numerous pharmacological studies, these findings do not always represent the clinical therapeutic superiority. Therefore, the clinical benefits of multi-component combinations must be subsequently confirmed in rigorous clinical trials.” 

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Claims in marketplace 

How do these claims of producing synergistic effects play out in the modern dietary supplement marketplace? Let’s take a look. 

Many multi-ingredient formulas make synergistic claims, if all the ingredients seem to be aimed in the same direction.  

For example, NOVUS Labs, a fairly new company in the anti-aging space, says one of its products, NOVOS Core, contains “12 natural, FDA-approved ingredients that synergistically target 12 causes of aging.” 

These claims are alluring even for marketers with long histories, such as Standard Process, a family-owned, nutritional supplement company that’s been in business for over 90 years. The company sells a product labeled as “OPC Synergy” marketed for “cognitive health, brain health, brain support and eye health.” It contains a mix of extracts and whole plant juice powders from buckwheat, green tea, grape seeds, carrots, bilberries and red wine. 

At least one company uses “synergy” as part of its name. And the multi-level marketing company LifeVantage was founded on a product called “Synergizer,” and that term is still used years later as part of the more recent product names. 

These are just a few examples of the many claims of synergy found online or on shelves. The products detailed above appear to be made with high-quality ingredients. But are they formulated based on the “Jun-Chen-Zuo-Shi” model or a similar guiding principle? Are they comprised ingredients chose from a supplier's list that are all headed in the same general direction? Are they a team, in other words, or just a crowd? 

Respecting the history 

Longtime herbalist and formulator David Winston, founder of the firm Herbalist and Alchemist, said the synergy concept has a long history, which is gradually being backed up by studies done to Western evidentiary standards. 

“The concept of synergy is not a modern invention. The idea of herbal synergy is part of almost every traditional practice of medicine,” he said. “TCM, Ayurveda, Siddha, Unani-tibb, Kampo and Physiomedicalism all have the concept of synergy as an integral part of their medical practice.” 

“Over the past 20 years, synergy has become a popular area of research in both herbal and pharmaceutical studies,” Winston added. “Now we have over 100 clinical trials done in the last two decades conclusively showing that synergy is a very real phenomenon.” 

Roy Upton, founder of the American Herbal Pharmacopoeia and a practicing herbalist, said the term “synergy” has applied to how products were put together, and, increasingly, how they’ve been used. 

“The idea of combining herbal ingredients in a manner that creates synergy is inherent in both Ayurveda and TCM,” Upton said. “The ingredients are either combined per the specific nature of the herbs (based on taste, smell, action) or the specific pattern of the individual being treated. Later, the word was used to describe how natural health care practitioners practiced, integrating diet, lifestyle, supplements, physical activity, etc. as well as to describe herbal formulas.” 

Does the supplier have substantiation? 

Whether products formulated in the modern, Western dietary supplement idiom can deliver on those promises is another matter. 

Shaheen Majeed, global CEO and managing director of the ingredient supplier Sabinsa, recommended companies review a supplier’s science when deciding to formulate a product along synergistic lines. 

Turmeric is one of the mainstays of Ayurvedic preparations and the bedrock of the curries that are central to Indian cuisine. Another main player in curries is black pepper, and it turns out there was more to this story than mere flavor considerations. There is a bioavailability synergy at work, something that Sabinsa has proven with its years of characterization and clinical work done on BioPerine, its branded black pepper extract. 

“Sabinsa has conducted research on the increased bioavailability of a variety of herbs, vitamins, and minerals with the addition of BioPerine, including beta-carotene, CoQ10, curcumin, resveratrol, iron, selenium and vitamin B6. All of them showed noticeable improvement in bioavailability with BioPerine. We are currently doing research into additional popular supplement ingredients and seeing similar results,” Majeed said. 

Experts: Few claims in marketplace pass muster 

Mark Miller, Ph.D., a consultant with a long history of botanical product development expertise, said few companies using the term in the U.S. marketplace seem to understand the full underlying principles. 

“It all starts with what is the core problem to be solved, the core, central driver for these events and how are these central processes regulated and controlled. If that is not clear, then it is impossible to accurately use the term ‘synergy,’” he said. 

In the worst-case scenario, Miller said, claims of synergy can be little more than window dressing. 

“It is a nutritional fashion statement, a ‘this goes well with that’ type of approach,” he said. 

Upton said all too often companies approach this question from a marketing standpoint, with the scientific underpinning or traditional knowledge considerations left by the wayside. 

“I would presume that most marketers use the term synergy uncritically and without real support, traditional or scientific,” he said. “Most American-made supplement formulas tend to be ‘everything and the kitchen sink’ approach to formulation.” 

Don’t throw baby out with bath water 

Winston cautioned against assuming the word “synergy” when used on a label or in marketing language is always a throwaway term akin to “new and improved.” But he said the real shame is that few products in the modern marketplace can clear a high bar of efficaciousness. 

“It is not hot air, but claims of synergy need to be based either on long-term traditional use (Dui Yao) or research,” Winston said. “Simply combining multiple ingredients is no guarantee of synergy. There are many negative studies which showed that adding one herb to another had no increased benefit and some studies showing the combination was less effective than the individual herbs.” 

“Synergy is one of the primary keys to effective herbal medicine, but without understanding the basis for how synergy occurs, the types of synergy and knowing how to avoid pharmaceutical incompatibilities, these products simply will not work,” Winston concluded. “When I go into stores and look at herbal/nutritional formulas on the shelf, I can tell within 30 seconds whether the person (or committee) that designed the product actually understood synergy and formulation or simply threw a bunch of things together and called it a day.”