Whole Herb vs. Standardized Extracts vs. Isolated Bioactive Constituents

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When using botanical medicine, which is best?

It often seems that dietary supplements come with endless array of options, particularly in an online world where one can find hundreds of choices with a seemingly simple search term such as “probiotics.” Similarly, with vitamins and minerals, we are offered so many forms – not only of the active ingredient, but the delivery format as well. Would you like your vitamin B12 as a liquid, lozenge, or capsule? Adenosylcobalamin, cyanocobalamin, or methylcobalamin? Magnesium chewables, effervescent powder, or tablets? Magnesium glycinate, citrate, oxide, or malate?

With botanicals, the array of choices is no less, and possibly is even more. For delivery, we are commonly offered tinctures, glycerites, solid extracts, teas, and capsules. However, with botanicals, the format (e.g., tincture versus glycerite) and specifics of how it is produced (and even when it is harvested) also impact the final product we are getting. For example, with a tincture, the potency and botanical constituents found in the final product are affected not only by the ratio of botanical parts to liquid, but also by the percentage of alcohol and water used to produce the tincture.

With a tincture, the potency and botanical constituents found in the final product are affected not only by the ratio of botanical parts to liquid, but also by the percentage of alcohol and water used.

Fortunately, professional supplement companies that employ physicians, chemists, and/or herbalists are well aware of how these variations can affect a final product. However, it is still worth learning about what may make one product different than another, particularly where whole herb versus standardized extracts versus isolated bioactive constituents is concerned. Herein, we discuss the differences between these products so you can make a (more) educated choice when buying botanical-containing nutritional supplements.

Whole herb products

The term “whole herb”, although commonly used, is actually a bit misleading. Despite this referring to a blend of all the constituents naturally found in the herb, it most often is from an isolated part of the plant. Some examples of this are ginger (Zingiber officinale), turmeric (Curcuma longa), and American ginseng (Panax quinquefolius) – for each of these, when used medicinally, the term whole herb usually refers to the rhizome; and for plants like Oregon grape (Mahonia aquifolium), pau d’arco (Tabebuia spp.), and white willow (Salix alba), whole herb refers to the inner bark. This is due to the fact that medicinal products commonly use these parts of the plant. Similarly, for other medicinal plants we commonly use the aerial parts (leaves and flowers, e.g., lavender), leaves (e.g., stinging nettle), or seeds (e.g., pumpkin seed). Noteworthy, when labeled correctly, a product should still indicate which part of the plant that is used.

Unfortunately, it is not incredibly uncommon that non-standardized whole herbs have been shown by testing to not contain these active fractions – and possibly not even be the plant they are stated to be. Thus, it is best to choose products from companies that perform the appropriate third-party testing and disclose their testing results.

For many botanical products used medicinally, the primary biologically active constituents (known as bioactive compounds) found in them are largely known. Active constituents tend to be found at higher amounts in the medicinal portion of the plant (as compared to other portions of the plant) – and can be identified by scientific techniques such as high-performance liquid chromatography (HPLC).[1] Examples of active constituents, using the same botanicals discussed previously are gingerols,[2] curcuminoids,[3] ginsenosides,[4] berberine,[5] naphthoquinones,[6] and salicin.[7]

The whole herb should thus contain these active compounds as well as all of the other fractions of the indicated portion of the plant. Unfortunately, it is not incredibly uncommon that non-standardized whole herbs have been shown by testing to not contain these active fractions – and possibly not even be the plant they are stated to be.[8] At times, it has even been shown that botanical ingredients have been adulterated either deliberately or accidentally (particularly with sourcing from China),[9],[10] giving further importance for identification and contaminant testing. This is why one should take care when using botanicals (and all other forms of nutritional supplements) to choose products from companies that perform the appropriate third-party testing and also disclose their testing results (especially when requested) to show that a product is what it is stated to be.

Whole herb products without any standardization are usually cheapest – but obviously may not be best. With each of these considerations, it doesn’t take much reasoning to understand why one might prefer a standardized extract – the upsides of which we will discuss next.

Standardized extracts

Given the previous discussion, it doesn’t take much more explanation for one to grasp what a standardized extract is, or why it may be desirable. Standardized extracts include the whole herb but are standardized to require a certain amount of one or more active constituents. Botanicals that are commonly standardized include ginkgo (standardized to flavone glycosides and terpene lactones[11]), cranberry (standardized to proanthocyanadins[12]), milk thistle (standardized to silymarin[13]), rhodiola (standardized to rosavin and salidroside[14]), ashwagandha (standardized to withanolides[15]), licorice (standardized to glycyrrhizin or glycyrrhizic acid[16]), and many, many more. Basically, by this day and age, any botanical that has a tradition of medicinal use has been researched at least to some extent (often motivated by the pharmaceutical industry to spur new drug development), and thus we have an idea of what the active constituents are that it could be standardized to.

Standardization of botanical extracts also enables us to perform higher quality clinical research.

Standardization of botanicals does many things. Firstly, it gives companies that use them a compound that can be tested for to ensure the supplement meets a certain quality standard. Secondly, it gives consumers a means via which they can compare different supplements not only for quality, but also so the supplement can be correctly dosed. Thirdly, standardization enables us to perform higher quality clinical research with botanical supplements. Imagine this – how would one study an herb effectively if in one study subjects were taking 50 mg of a substance, known to be active in the human body, while in another study they were only receiving 5 mg, or even worse – none! Clearly, having a placebo-controlled clinical study would be almost useless in the latter example.

Isolated bioactive constituents

Finally, we come to the third variant – isolated bioactive constituents. With all this discussion so far, it is easy to make the leap to the conclusion that this option may be the best. But hold on, not so fast! Let’s take a closer look at times when this may, or may not, be the appropriate conclusion.

You may or may not be aware of it, but if you use nutritional supplements, you probably have been exposed to some products that are isolated, botanically derived, bioactive constituents, or tend to be nearly that. An example of a product commonly used which can be classified as such is quercetin, a flavonoid commonly used to help reduce the symptoms of allergies and associated immune system activation.[17],[18] Many turmeric products also contain very high (>90%) levels of curcuminoids,[19] which are the primary substances mediating turmeric’s anti-inflammatory activity. (However, for turmeric this is only part of the story, as the poor bioavailability of these molecules is a huge issue.) Diindolylmethane (commonly known as DIM) is another common supplement that is an isolated molecule, but is produced naturally in our gut (from indole-3-carbinol) when we eat cruciferous vegetables.[20]

Using an isolated bioactive constituent neglects potential synergistic effects the primary bioactive components have with other compounds found in the herb.

Given these well-known dietary supplements that are isolated bioactive constituents, one might wonder why this is not common practice with other botanically based products. The main answer that many would provide for this question is that this neglects the potential (and sometimes scientifically proven) synergistic effects the primary bioactive components have with other compounds found in the herb. However, other reasoning includes the high cost that would be required to obtain the single bioactive compound, and the general, holistic view that botanical medicine encompasses more than just a biological, proven physical response.

One example of this is the resin of Pistacia lentiscus var. chia, commonly known as Chios mastiha or mastic gum. Mastic gum has numerous bioactive compounds – which research has shown are more effective when taken together as a whole powder rather than supplementation of the isolated compounds found within it.[21] Oftentimes, the whole herb is more effective than isolated fractions because the bioactive compounds activate different critical pathways or intersect with a condition by multiple different mechanisms. Mastic gum is particularly effective for ulcers related to Helicobacter pylori because it helps to resolve the infection,[22] reduces excessive neutrophil activation,[23] and promotes healing of the gastric mucosa.[24]

It has been proposed that the flavonoids and polyphenols found in white willow bark act synergistically with salicin and its metabolites to produce its observed therapeutic action.

This is also true for white willow bark, whose active constituents include salicin as mentioned.[7] In the body, salicin is converted to salicylic acid, the same molecule which aspirin (acetylsalicylic acid) also produces. Preparations of white willow bark have been used for the treatment of fever and rheumatism, dating back to 4000 BCE, and led to the discovery of acetylsalicylic acid in the early 1800s.[25] However, it has been demonstrated that typical doses of white willow bark do not produce enough salicylic acid to have an analgesic effect.[26] Thus, it has been proposed that the flavonoids and polyphenols found in the bark act synergistically with salicin and its metabolites to produce its observed therapeutic action. Noteworthy, despite the production of salicylic acid, high doses of white willow bark have not been shown to damage the gut mucosa or have an antithrombotic effect such as aspirin has.[27]

Artemisia annua, commonly known as sweet wormwood, is also well known for its primary active compound – artemisinin. Artemisinin-based therapies are commonly used in integrative medicine and outside of the U.S. for the treatment of malaria[28],[29] and they also find use in oncology settings.[30],[31] However, similarly to antibiotic-resistance, resistance of the parasite Plasmodium falciparum (which causes malaria) to artemisinin has been on the rise.[32] Numerous studies point to synergistic effects that the many other compounds in A. annua have with artemisinin, suggesting that treatment may be more effective if portions of the whole herb were used in combination with this main bioactive compound.[33],[34]

These, of course, are but a few examples to show that there is an array of reasons for the many different forms of botanical products found on the market. It is not uncommon to find that nutraceutical companies pick and choose from all of these options – at times, enhancing a product that contains an isolated compound with some of the whole herb, or combining standardized extracts of a primary ingredient of a formula with the lower cost whole herb of a less important botanical in a blend to access the synergy they have, but to not break your pocketbook!

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