Adaptogens: from herbalism to clinical nutrition

Introduction: adaptogens

An ever-increasing number of active ingredients qualified as adaptogens are currently emerging from the nutraceutical market. And for a good reason: the great fame of some of them in traditional medicine and their pleiotropic health benefits on immunity, stress, and fatigue, make them highly successful and effective active ingredients.

But what is so special about adaptogens? 

From a functional perspective, adaptogens were historically described as "medicinal substances which induce an increased state of nonspecific resistance in the body". They are plants or fungi that typically increase the body's resilience to external stress (physiological, emotional, or even physical) and promote an overall return of physiological functions to a state of homeostasis.

From a biochemical point of view on the other hand, research shows that adaptogens are often characterized by a diverse molecular profile that combines bioactive secondary metabolites (terpenes, phenols, alkaloids, etc.) and specific polysaccharides, mainly found in the plant’s roots (and sometimes the fruits).

Could it be that the outstanding pleiotropic effects of adaptogens are in fact due to their particularly diverse molecular profile compared to other medicinal plants? Although research has not yet sufficiently highlighted this aspect, it seems that molecular diversity might indeed be a crucial factor of adaptogenic efficacy.

The future of adaptogens lies in clinical nutrition

Far from traditional plant concoctions, modern mainstream herbalism fits in a capsule. Deeply inspired by modern pharmacology, the nutraceutical industry has a tendency to consider botanicals as a source of a unique physiologically active molecule. Phyto-nutraceutical active ingredients are now often made of extracted and purified bioactive molecules with high therapeutic potential, intended to produce powerful / acute and targeted effects on the body; a pharma-inspired solution that has proven to be remarkably effective in the treatment of many pathologies.

This pharmacological conception, however, also has its limitations; it does not allow to fully harness and exploit the therapeutic potential of complex bioactive natural matrices with pleiotropic effects such as those of adaptogens. And this is because phytoactive enrichment or purification leads to the loss of a fraction of the full molecular profile.

In that regard, an interesting scientific approach to understand adaptogenic botanicals would be through clinical nutrition. Considering the plant as a functional food source of multiple phytonutrients and preserving their naturally complex bioactivity could lead to a better understanding of their systemic effects on the human body. A case in hand would be that of ginseng.

The case of ginseng

Panax ginseng C.A. meyer - Illustration by Botalys​

Korean ginseng (Panax ginseng C.A. Meyer​) is undoubtedly the most recognized and studied adaptogen in the world and deserves special mention in this regard. Indeed, the precious root has been used for millennia in traditional Asian medicine and has forged itself a fine reputation as a panacea thanks to its physical and mental stimulation potential and rejuvenating / revitalizing virtues.

Recent research has made it possible to highlight a family of particularly bioactive / high therapeutic potential molecules in ginseng: ginsenosides. These steroidal-structured saponins demonstrate numerous health benefits, from nootropic effects to hypoglycemic action, as well as immunomodulating and even anti-tumor properties. In particular, the noble / rare fraction, which includes the most bioactive representatives of ginsenosides, seems to confirm / explain most of the physiological effects attributed to ginseng in the Asian tradition.

However, it seems that ginsenosides alone do not explain the unique properties of ginseng. The global enthusiasm around this extraordinary plant has indeed led to an abundance of scientific data related to its characterization and to the potential contribution of other bioactive compounds to its effects on human physiology. To support this, we established a small review of some of the most prominent adaptogenic health effects of ginseng polysaccharides recently highlighted by scientific research.

- Ginseng and the neurological sphere

Ginsenosides, and in particular CK, Rg1, Rg2, Rg3, Rg5, Rh2 and Rk1, are strongly involved in the neurological benefits of ginseng. Indeed, research reports their significant neuroprotective [1] and nootropic potential which both lead to a positive impact on symptoms related to stress [2], depression [3-5] and mental and metabolic fatigue [6, 7]. Some ginsenosides also improve memory and learning capacities and could improve sleep through GABAergic pathway activation [8-10]. Ginsenosides Rg1, Rg3, Rg5, Rk1 and Rh2 also have significant potential for the prevention and early treatment of neurodegenerative diseases such as Alzheimer's [11-13].

Although little research has been done in this context so far, the anti-fatigue effects of ginseng root polysaccharides / pectins have also been demonstrated in an animal model of Chronic Fatigue Syndrome [14, 15], often correlated with depression.

- Ginseng and the immune system

Several ginsenosides (including in particular Rg1, Rg3, Rh1, Rh2, Rh4, Rk1) also exhibit immunomodulating / immunostimulating [16], anti-inflammatory [17, 18] and cytotoxic / anti-tumor [19] properties and may even present therapeutic potential in the treatment of autoimmune diseases such as endometriosis [20, 21].

Furthermore, ginseng polysaccharides, and in particular their acid fraction (including ginsans), have been investigated for their immunomodulating / immunostimulating effects [22]. In addition to potentiation of the immune response by stimulating the activity of macrophages and their cytotoxic mediators [23] and by increasing the number of B and T cells [24], ginseng polysaccharides also have significant anti-inflammatory activity and antioxidant [25] and anti-adhesive properties [26].

- Ginseng and metabolic regulation

Ginsenosides, including Rb1, Rg1, Rg3, Rg5, Re, Rh2 and CK, have great potential for metabolic regulation and prevention and treatment of diabetes and its complications [27]. Among the main effects shown are insulin-resistant activity [28], regulation of blood glucose and lipids levels as well as anti-adipogenic / anti-obesity effects [29] linked to PPARγ receptors downregulation.

Panaxans, a family of 21 peptidoglycans in ginseng, have demonstrated dose-dependent hypoglycemic activity. Several studies have shown that intraperitoneal administration of panaxans A-U [30-34] in healthy mice induces a dose-dependent significant reduction of blood glucose level, as well as hypoglycemic properties.

- Ginseng and metabolism

Despite their demonstrated prebiotic and immunomodulating potential, the number of scientific studies on ginseng polysaccharides remains relatively limited. Often co-extracted with ginsenosides, they are nevertheless of great pharmacological interest; the regulatory effect of polysaccharides on the microbiota could indeed promote the biotransformation of precursors into rare ginsenosides, induce an improvement in their pharmacokinetic parameters and their intestinal absorption rate. These effects would therefore lead to a better systemic exposure of ginsenosides in the presence of polysaccharides [35, 36], particularly in the metabolic context [37].

In addition to polysaccharides, ginseng contains many other bioactive molecules with high therapeutic potential that would deserve further study. This is particularly the case for:

• gintonin​, a protein with high therapeutic potential for degenerative neurological and motor diseases [38].
• polyacetylenes ​such as panaxynol and panaxydol, with anti-platelet aggregation [39] and cytotoxic action [40] respectively.
• alkaloids ​like choline, which shows positive effects on blood pressure, memory or fat accumulation [41].

To conclude, ginseng perfectly embodies what modern pharmacology has to learn from traditional medicine. Although each of its bioactive molecules have demonstrated high efficacy on their own, it is highly probable that the “true” adaptogenic benefits of ginseng are brought about by their combined effects and interactions.

Full-spectrum - the essence of adaptogenic benefits

Everything seems to point at the importance of preserving a full-spectrum molecular profile to achieve the complete adaptogenic health effects of ginseng. Moreover, could this also be the case for other botanicals that fit in the biochemical or traditional definition of adaptogens?

There is indeed an increasing amount of evidence that suggests that adaptogen-derived polysaccharides significantly contribute to their pleiotropic benefits. Table 1 summarizes some of the demonstrated health benefits of polysaccharides extracted from six adaptogenic plants.

Table 1 - Health benefits of six adaptogenic plants polysaccharides​

Polysaccharides are indeed the most glaring example of bioactive molecules that have remained in the shadow of secondary metabolites. They nevertheless demonstrate remarkable effects on the immune, metabolic and even neurological spheres. In addition, their prebiotic potential and their significant regulatory effects on the intestinal microbiota would have a crucial influence on the absorption and bioavailability of certain families of active molecules.

Beyond a direct physiological action through the involvement of secondary metabolites in various metabolic cascades, it would appear that the molecular diversity of the bioactive matrix, in particular specific polysaccharides, may also contribute to the systemic effects and broad-spectrum efficacy of adaptogens.

Adaptogens should no longer be regarded as a sum of active molecules, but rather as a complex matrix endowed with synergistic and multi-target properties, full of unsuspected potential for human health.

Time for a new standard

Adaptogens in general beautifully capture the complexity of the effects of herbal remedies on human physiology. Their pleiotropic effects suggest that the variety of bioactive natural molecules contained in the plant matrix are not only involved in a wide variety of metabolic cascades, but also that they may have combined / synergistic effects.

Even if the current state of research does not yet allow us to fully understand these synergies, research points at an increased bioavailability and effectiveness of full-spectrum (multimolecular) preparations of adaptogens compared to their purified extracts (monomolecular). The obvious parallelism between the spheres of action of secondary metabolites and plant polysaccharides strongly suggests an overlapping of their benefits.

The full potential of “true adaptogens” could therefore only be achieved with full-spectrum botanicals that preserve the complete molecular profile of the plant. Despite their demonstrated pharmacological efficacy, using extracts potentially means forgoing the complementary and / or combined effects of the various components of the plant.

But the varying quality of botanical extracts on the market makes it difficult to obtain solutions that are natural, effective and safe. Indeed, two major challenges linked to botanical extracts of agricultural origin remain: the significant risks of contamination from pesticides and heavy metals, as well as the considerable difficulty of standardizing (from one batch to another and over time) of raw materials of varying composition.

The transposition of the principles of phytotherapy to modern pharmacology, and in particular in a clinical context, thus requires the production of botanical species of pristine quality; a standard that seems unattainable for natural nutraceutical active ingredients from agriculture.

- Botalys: clinical grade full-spectrum adaptogens - phytotherapy 2.0

At Botalys, we believe the future of adaptogens lies in clinical nutrition. We have dedicated 10 years to exploring botanical biodiversity and building in-depth expertise on the therapeutic potential of their phytonutrients. We believe that harnessing the full potential of plants goes hand in hand with the utmost respect of their (original) nature, their environment and - most importantly - the consumers' health.

Botalys aims to push the boundaries of the world of medicinal plants and pave the way for a new standard in the nutraceutical sector to ensure the quality, efficacy, safety and sustainability of medicinal plants. By combining the full-spectrum approach with innovative indoor vertical farming technology, Botalys produces clinical-grade adaptogens that are naturally rich in a wide range of active substances while ensuring a very high degree of standardization and purity.

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