Ginseng & Healthy Aging

Healthy Aging is becoming one of the biggest challenges in modern health; life expectancy is at an all-time high and people aspire to live longer and healthier lives.

At the same time, the approach to health is shifting from the alleviation and treatment of established health conditions to the prevention and delaying of their onset; and while the key-role of diet and lifestyle is no longer debated, that of supplementation is becoming increasingly important in this context.

Nutraceutical brands have embarked on a race to offer an ever-expanding range of preventive solutions, targeting consumers as young as 40 to support them in the inevitable process of aging. And despite dynamic innovation in the industry, many products continue to draw inspiration from foods and plants known for their anti-aging potential since the dawn of time.

This is particularly the case for Ginseng – undoubtedly the most famous medicinal plant in traditional Asian medicine, and for good reason: its virtues as an elixir of longevity have earned it more than 3000 use and a place of honour in the Chinese, Korean and Japanese pharmacopoeias.

But to what extent does modern science support the effects of the millennial panacea on human health and its potential for preventing age-related discomforts and pathologies ? Could research earn ginseng a new-found glory in modern medicine through the backing of its legendary properties with solid science ? Could an ingredient like ginseng fit the current market’s trends and needs ?

In this article, we offer an overview of the Healthy Aging segment of the Nutraceutical sector and we review the existing bibliography on the anti-aging properties of Panax ginseng roots to find out.

1. THE HEALTHY AGING MARKET

Healthy aging is one of the leading trends on the Nutraceutical market today – and one that will inevitably keep going strong and shaping the Nutraceutical landscape in the current demographic context.

The current demographic transition is a major factor in the development of the Healthy Ageing offer on the Nutraceutical market. According to the World Health Organization (WHO), the population over 60 is expected to double in the first half of the 21st century and reach 2,1 billion by 2050.

Given the decreasing birth rates, the population over 60 years old will increase from 14% of the current global population to 21,4% in 2050. In Western countries like France, population over 65 is expected to go from 17% to 26% in the same period (EU Commission data). The population over 80 years old on the other hand, is expected to triple by the middle of the century and represent 4,4% of the world population.

This unprecedented increase in life expectancy has been leading to an explosion in the incidence of age-related non-communicable diseases (NCDs), also strongly favoured / supported by unhealthy modern lifestyles. The WHO estimates that NCDs currently account for as much as 71% of global deaths and has been emphasizing the crucial role of prevention in controlling their incidence for more than a decade.

Furthermore, numerous medico-economic studies agree that prevention – particularly through nutritional supplementation – would allow a significantly reduce the economic burden that the health care of our aging populations will represent in the forthcoming future.

Not only are adults and seniors a growing portion of our societies, but they are also target of choice for Nutraceutical brands. More and more consumers over the age of 40 are taking a proactive, preventive approach to preserving their health and living longer, healthier lives – and are turning to nutritional and natural supplements to do the job. Adults in the earliest phases of aging are increasingly aware of the importance of investing in their future well-being and they also have more financial means to do so.

Indeed, in the UK only, the proportion of dietary supplements users over the age of 65 reached 40% in 2019 and no less than 27% in Italy. In North America, CRN Consumer Survey on Dietary Supplements reported that the proportion of supplement users goes up to 81% for +55 year/olds.

In 2020 (pre-covid), Euromonitor International’s Health and Nutrition Survey also reported that 32% of global respondents aged 60+ took vitamins and dietary supplements on a daily basis – twice as much as 15- to 29-year-olds (16%).

Market needs are also changing; consumers are looking for comprehensive tailored-made solutions to address their health and well-being in a broader sense; they no longer seek targeted functional product promises such as fatigue, joint health or cholesterol – which they still largely rely on their doctors to prescribe – but rather “Vitality”, “Antioxidant” and “Metabolic balance”. They are willing to start early if it means they will maintain their quality of life in the future without having to swallow a pillbox of meds every morning.

In addition, natural plant-based, clinically proven and sustainably sourced remain very attractive purchase factors for this category as well.

The major health concern of seniors echoes the most widespread life-threatening health issue in our populations: cardiovascular health (cholesterol, blood pressure and related risks of heart attack or stroke). Second comes a major factor of well-being: mobility. Finally, energy and brain function – which includes the preservation of cognitive faculties, focus and memory – also remain among the priorities for + 50 consumers. On the contrary, applications like weight management are relegated to the background in favor of the treatment solutions for the consequences of sustained overweight on health.

In terms of applications, Healthy Aging is a very fragmented market with many areas of focus; from general categories like cognitive health and mobility (which includes joint health, bone health and vitality), to holistic wellness (menopause) and functional positionings (vision, diabetes, memory) and even cosmetic applications (anti-aging of the skin, hair loss).

A striking example of this transition is the transition from vitality and mobility segments into the more comprehensive concept of “Active living”. This category not only addresses mental alertness, physical energy, and joint / bone health but also, and increasingly so, the support of sports performance. Indeed, the segment is seeing the emergence of a great number of products borrowing their codes and promises from sports nutrition, to address a growing portion of mature consumers highly invested in sports practice and wishing to support and boost their performance.

Another emerging trend to which the development of the healthy aging market is contributing significantly is that of Nutricosmetics. Indeed, maintaining a youthful appearance remains an important drive for the consumption of nutritional supplements in the context of aging. In addition, the in&out and preventive approaches are taking a growing space in the cosmetic market and present significant applicative potential for nutraceutical ingredients with benefits for skin, nails or hair health. The fascinating segment of nutricosmetics will be the subject of a separate article in the future.

Contrary to millennials, a large portion of over 50 consumers rely on the advice of a prescriber or pharmacist to choose their products. This contributes to keeping the offer on Healthy Aging relatively medicalized, since Nutraceutical brands must first and foremost convince health professionals.

However, this tendency is destined to shrink as digital-era generations of seniors get older and as the market transitions from treating age-related discomforts to preventing and slowing their appearance. And new innovative brands are addressing the younger portions of aging adults with more lifestyle formulations and positionings. The market seems to be evolving with its future consumers and is seeing tremendous innovation at all levels.

In terms of ingredients, formulations are extremely diverse and address such a diversity of applications that it is difficult to establish an exhaustive classification. However, several important categories stand out in the market:

  • Vitamins & Minerals, used as a treatment base to prevent age-related deficiencies and protect the normal functioning of vital functions.

     

  • Antioxidants like glutathione, resveratrol, hydroxytyrosol, green tea catechins, or anthocyanins from berries. They help slow down the oxidation process and protect cells from ROS damage throughout the body. Lutein and zeaxanthin are particularly known for their potential to prevent macular degeneration and therefore protect vision.

     

  • Anti-inflammatory compounds like curcurmin from turmeric, boswellin from Boswellia or gingerol from ginger to help fight local (joints, intestines) and low-grade generalized inflammation.
     
  • Coenzymes like NAD+ (and its precursors) and CoQ10. They naturally decline with age and are involved in mitochondrial metabolism and essential to cellular energy production.

     

  • Hormone-regulating plants like phytoestrogens for menopause (hops, soy, flax seeds) or plants with androgenic benefits for prostate or hair loss (saw palmetto), to help attenuate the important hormonal changes consumer go through as they age – or phytosterols to lower cholesterol.

Traditional anti-aging plants from ancient pharmacopeias are also regaining great interest of the public. Inspired by Asian Traditional Medicine, Ayurveda or traditional phytotherapy, they fit right in the current trend for natural safe plant-based solutions. Amongst the most well-know are turmeric for inflammation and joint health, berries like aronia for their antioxidant properties, gingko for memory, and ginseng for energy – to name a few.

The Healthy Aging segment also draws the inspiration for its key active ingredients from the diets of the world’s longest-lived populations. This is particularly the case for the Mediterranean diet, which is rich in antioxidant foods and fatty acids from fish (omega-3) and associated with a lower risk of diabetes and cholesterol, cardiovascular disease and even neurodegenerative diseases. Countless nutraceutical products capitalize on the natural antioxidant properties of olive oil (hydroxytyrosol), grapes (resveratrol) or even pomegranate (punicalagins) for the maintenance of good health and longevity.

Finally, the ubiquitous trend of microbiome is also expanding into the Healthy Aging market. There is a growing interest in bacterial strains that promote longevity, and many studies show that the microbiotic balance plays a key role in the prevention of inflammatory and oxidative syndromes at the origin of aging.

2. GINSENG & HEALTHY AGING

From a biological perspective, aging represents the accumulation of cellular damage in the body over time, slowly leading to a less efficient function of organs and metabolic processes. In turn, physiological dysfunctions lead to a decline in mental, physical and even vital functions that are expressed by a variety of so-called geriatric syndromes.

In addition to genetic and socio-economic predispositions, the onset of symptoms and diseases related to aging is strongly impacted by lifestyle risk factors such as diet, stress, physical fitness and unhealthy habits (tobacco and alcohol, living in polluted areas); all of which can be aggravating factors.

Research on rejuvenating and longevity solutions is still at its first steps but existing offer generally capitalizes on fighting two of the main mechanisms of aging: exposure to oxidative stress and low-grade inflammation.

The known antioxidant and anti-inflammatory effects of ginseng and its bioactive molecules may therefore have far more ramifications and health benefits than will appear in the tradition of Asian medicine.

2.1. Neurological benefits

According to the WHO, dementia – or the progressive deterioration of cognitive function with age – affects more than 55 million people worldwide. Among the 10 million new cases of dementia each year, between 60 and 70% are cases of Alzheimer’s; it is also one of the main causes of disability adjusted life years (DALYs).

To this day, no effective pharmacological treatment has been found, most scientific literature rather pointing at the importance of prevention in the delaying on its first symptoms and the slowing of its development.

  • Neuroprotection & Cognitive performance

A significant number of studies support the positive neurological potential of ginseng and its bioactive compounds. Rg3 in particular shows neuroprotective properties [1-8]. This rare ginsenoside has also been identified as a “shield” against cognitive deterioration in multiple experimental models [9-10]. The benefits of Rg3 on Alzheimer related mechanisms also look very promising [11-14].

In addition, Rg5 & Rk1 have recently been identified as beneficial in the neurological area, including depression [15] and sleeping issues [16]. However, most of the literature on the neurological impact of these ginsenosides, is referring to neuroprotective properties [17] including preservation of cognitive capacities [18-19] and positive impact in neurodegenerative models [20]. In addition, it has been shown that Rg3, Rg5 & Rk1 may have memory enhancing effects, as they were shown to significantly reversed scopolamine – induced memory dysfunction on top of neuroprotective effects [21].

 

  • Fatigue

Ginseng is traditionally considered a natural tonic and has largely been investigated in that sphere. In fact, ginseng preparations and a variety of its bioactive components – among which saponins [22] polysaccharides [23-24] or oligopeptides [25] – have revealed promising potential for the treatment of age or chronic illness-related fatigue.

More specifically, rare ginsenoside Rg3 seems to play an important role in ginsengs ergogenic properties. Rg3 has been reported to have positive impact on fatigue, both from a metabolic [26] and a neurological [27] standpoint. In addition, it has been shown to “mimic exercise training” on cardiac mitochondrial system [28], suggesting new application potential for sport nutrition.

 

2.2. Metabolic benefits

Metabolic disorders are one of the major health concerns deriving from unhealthy diets and lifestyles, although genetic predispositions also play a role in their onset. Closely correlated with the boom of obesity, chronic metabolic dysfunctions like diabetes can cause serious damage to the cardiovascular, uro-digestive, and neurological systems and constitute a great and increasing economic burden to society.

According to the WHO, diabetes affects more than 400 million people worldwide and was the direct cause of 1,5 million deaths in 2019. In addition, 48% of deaths from diabetes occur before the age of 70 and would therefore be preventable.

Ginseng, and in particular noble ginsenoside-rich black ginseng, has also demonstrated significant efficacy in the context of both glycaemic and lipidemic regulation [29].

Experimental data points at the efficacy of the ginsenoside tandem Rg3, Rg5 and Rk1 in multiple models [30-33]. Indeed, an increasing number of scientific data shows the positive impact of these three bioactive ginsenosides on sugar and fats metabolism, which clearly suggests considering them an option for early stages of “metabolic imbalance”. 

Even separately, Rg5 [34-35] and Rg3 [36-38] have been identified as a promising adjuvant treatment for diabetic patients. Rg3, shows significant balancing effect on blood sugar [39-42] and potential benefits on complications related to the diabetic condition [43-46].

2.3. Cardiovascular benefits

According to WHO estimates, cardiovascular diseases (CVDs) are the leading cause of death worldwide. Mainly represented by heart attacks and strokes, CVDs account for no less than 38% of all premature deaths (under 70) due to NCDs each year, making in one of the top health topics for both patients and health authorities.

Although current prevention strategies mainly address behavioural risk factors such as unhealthy and sedentary lifestyles, obesity and alcohol and tobacco use, dietary supplements brands are also addressing the issue with cholesterol and heart health natural solutions.

Numerous research supports the cardioprotective potential of ginseng. Studies show oral administration of ginseng extracts can have positive effects on both vascular tone and function [47-49] and cardiac function [50], as well as anti-thrombotic potential through anti-platelet aggregation effects [50-51].

In terms of bioactive molecules, Rg3 has revealed beneficial against hypertension [52-53] and has shown potential as a cardioprotective [54] and vasculoprotective [55] solution. Rg3 has also demonstrated efficacy in experimental models of atherosclerosis [56-58]. In addition, Rg3 seems to have beneficial effect on osteoporosis-related mechanisms [59-61].

On the other hand, scientific data on the cardiovascular benefits of Rg5 & Rk1 is still relatively limited. Current research does however seem to confirm the cardioprotective [62], vasculoprotective [63] and anti-aggregation activity [64] of these saponins. In addition, Rg5 promotes angiogenesis and shows strong vasorelaxant properties [65]. These preliminary results thus seem to point to the efficiency of those rare ginsenosides in a comparable manner than that of Rg3, which should encourage additional research for Rg5 & Rk1 applications in this field.

2.4. Joint & bone health

Joint & bone health are two major factors in preserving mobility at an old age. Chronic joint inflammation – in particular arthritis – can be very painful and disabling and bone tissue fragilization (osteoporosis) significantly increases the risk of fracture.

Rare bioactive forms of ginsenosides were identified as beneficial for bone health in different models.

Several studies showed improved growth, differentiation, and proliferation of murine preosteoblastic cell lines upon application of bioactive ginsenoside tandem Rg5:Rk1 [66] and Rg3-enriched fermented red ginseng [67].

Rg3 was also proven to inhibit osteoclastogenesis, and thus reduce bone resorption, which suggests potential applications for osteoporosis [68-69]. Other potential mechanisms of Rg3 efficacy in alleviating aluminium-induced osteoporosis were also uncovered in another study, pointing at an increased resistance to oxidative stress, growth factor regulation and facilitation of bone formation [70].

Finally, ginseng noble ginsenosides have shown potential for prevention and treatment of cartilage degradation in osteoarthritis models. Rg3 has demonstrated higher proliferative and telomerase activity, leading to protective properties against chondrocyte senescence [71]. Rg5 on the other hand inhibits cartilage apoptosis and thus prevents cartilage degradation [72].

2.5. Other benefits

  • Regulation of autophagy

 The loss of autophagic capacity in human cells is one of the key processes of aging. Maintaining and restoring the physiological mechanisms of autophagy is thus a key strategy in developing treatment solutions targeting longevity. In this context, investigating the underlying autophagic mechanisms that may have earned ginseng its millennial reputation as an elixir of longevity could be of real interest for applications in healthy aging.

First, a 2016 study unveiled the protective effect and autophagy upregulation role of ginsenoside Rg3 in the context of prion-induced neuron cytotoxicity and mitochondrial damage [73], suggesting the saponin’s potential for the treatment of neurodegenerative diseases.

Rg3(S) also showed potential to reverse the effects of replicative senescence in Human Dermal Fibroblasts (HDFs) by restoration of ATP levels and the NAD+/NADH ratio [74] and induction of antioxidant enzymes like PRDX3 [78]. The mechanism behind it could be Rg3’s modulation of Akt-mTOR-sirtuin signaling to promote the biogenesis of mitochondria [75].

Another study later established the link between Rg3’s role on senescence regulation and autophagy in HDFs. Rg3’s was shown to induce autophagy and NRF2 antioxidant signalling (through promotion of AMPK activation), resulting in the abolishment of replicative and ROS‐induced senescence in HDFs [76]. Ultimately, Rg3 was shown to promote rejuvenation in skin aging, thus opening new research perspectives for its use in autophagy‐dependent antisenescence treatment strategies. The same AMPK activation mechanism was observed for Rg3-induced autophagy in the context of myocardial injury [77].

  • Skin anti-photoaging properties

The antioxidant properties of ginsenosides have also led them to be investigated for the prevention of skin aging, with potential for nutricosmetic applications.

Indeed, oral administration of red ginseng showed a significant inhibition of UVB-radiation related wrinkles on hairless rats’ skin, probably through inhibition of collagen degradation [78]. In human studies, red and enzyme-modified ginseng not only showed reduced various skin roughness indexes (i.e. wrinkles) but also improved the skin’s moisture and elasticity [79-80].

At a cellular level, Rg3-enriched ginseng extract has shown antiphotoaging effects on human dermal fibroblasts after exposure to both UV and IR [81]. Rg3 treatment also restored ATP mitochondrial dysfunction in skin cells damaged by UV irradiation, as well as to enhance the expression of antioxidant proteins [82]. Another study had also previously shown the stereoselective anti-photoaging properties of 20(S)-Rg3 on HaCaT human skin cells [83], through ROS-scavenging and MMP-2 inhibitory mechanisms.

  • Sexual function enhancement

Although clinical evidence is still largely suggestive on this matter [84], sexual function enhancement is one of the most widespread traditional applications of ginseng.

A recent study on a steamed ginseng extract suggested the interest of rare ginsenosides, in particular Rk1 and Rg5, in the recovery of erectile function [85]. In another paper, oral supplementation of Rg3 also showed protective effects against erectile dysfunction through antioxidant and anti-apoptotic effects in corpus cavernosum cells, in a murine model of streptozotocin (STZ)-induced diabetes [86].

  • Microbiotic benefits

Microbiotic health also appears to have a role in maintaining health at an old age, and ginseng may again provide benefits in this sphere. Indeed, diets rich in fermented foods have repeatedly been correlated with the extraordinary longevity of certain populations such as the Mediterranean or the Japanese diets – the latter even holds the record of the greatest number of centenarians within it.

We now know that microbiotic balance is an important health modulator intimately linked to physiological functions, from immunity to neurology and metabolism. On the contrary, states of dysbiosis and the chronic low-grade inflammation they cause are an increased risk factor for the development of age-related non-communicable (or lifestyle) diseases such as diabetes.

Recent research shows that several active compounds of Panax ginseng [87-88] – including specific polysaccharides [89-91] and bioactive ginsenosides like Rh4 & Rk3 [92-94] – have been identified as beneficial for the gut microbiota. While it is too soon to affirm that specific ginseng compounds could support seniors’ health through this microbiotic dimension, an increasing number of data points in this direction.

  • Hormonal deregulation

Ginseng also shows benefits for the alleviation of hormone-dependent conditions in both men and women. However, ginsenosides do not demonstrate estrogenic or androgenic activity despite having a very similar structure to that of steroid hormones.

In the case of androgenic alopecia – a hormone-related condition and predominant cause of hair loss in men – ginseng and several of its bioactive saponins have demonstrated significant clinical potential in both preventing / attenuating hair loss and stimulating hair growth at the follicular level. Rare ginsenosides inhibitory action of on 5α-reductase, a testosterone converting enzyme whose activity is correlated to the onset of androgenic alopecia, was found to be one of the mechanisms involved. This same inhibition mechanism was also identified as the main mode of action of saw palmetto in the treatment of prostatic hypertrophy, suggesting that ginseng may also have benefits in this area.

    On the other hand, ginseng also demonstrates a multi-target action on various menopausal discomforts – among which hot flashes, mood stability, sleeping issues and osteoporosis, and could thus help women through their peri-menopausal transition through significant symptomatic alleviation.

    CONCLUSION

    Ginseng is one of the most studied medicinal plants in the world, and therefore benefits from a wide range of scientifically proven properties of particular interest in the context of aging.

    The anti-inflammatory and antioxidant properties of ginseng and its active constituents give it a wide spectrum of action, ranging from regulation of autophagy to protection of cognitive (neuroprotection), cardiovascular (cardioprotection) and metabolic functions.

    Ginseng is also involved in alleviating age-related hormonal imbalances, with significant potential for menopause, osteoporosis and even hair loss.

    Finally, ginsenosides have an interesting potential to prevent the appearance of visible signs of aging on the skin and perhaps to address in a safe and natural way other problems at increased risk in the elderly such erectile dysfunction and intestinal dysbiosis.

    In conclusion, harnessing the full potential of this age-old panacea could open-up the path to new development opportunities in the market of Healthy Aging. Generally known for energy, ginseng’s use could very be well fit the needs of the sector and be used both as a stand-alone general well-being ingredient or in combination with other potent plants or nutrients active on more specifically targeted age-related health issues.

    Today more than ever, ginseng continues to live up to its age-old reputation as an elixir of youth, offering a wide variety of scientifically proven benefits for the prevention of age-related pathologies and the mitigation of geriatric symptoms.

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