The problem of heavy metals in herbal medicines

On the one hand herbal medicine is great, it tends to be more gentle, to not have withdrawals, allows synergistic combinations of herbs to create complex actions, and often is much milder in side effects. Tonic herbalism as taught by some practitioners of Indian and Chinese medicine emphasises taking specific herbs like ashwagandha or panax ginseng, long term as supportive agents for overall health and longevity. As long as the herbs suit the individual and there are no contra indications, this does not seem like an unreasonable idea. However, there is a danger in this, and that comes in the form of contamination, and is especially an issue using imported herbs from countries like China and India.

Contamination in herbs can be due to the presence of herbicides or pestidicides, but some of the greatest concern at the moment is the presence of heavy metals that may have accumulated in the plant whilst growing in polluted conditions (Ernst, 2002). This is particuarly true for countries with poor standards of environmental control and with terrible pollution problems. One such country is China, I was struck when travelling China some ten years ago by railway, how built up and polluted the city, countryside, and air was. It was not until we reached the Himalayan mountains far in the West until this dissapeared. It is important when practising herbalism that the user of herbs is aware of potential contamination issues in widely available supplements from abroad. It is sensible especially when dealing with herbs that come from countries, such as China and India, to ask for a certificate of analysis to determine whether the material has contamination with heavy metals. The company should be able to provide lab results.

Edzard Ernst writes in his review article, on the subject of contamination in herbal medicine, that, “…Woo reported the detection of toxic heavy metals that exceeded Singapore’s legal limits in 42 Chinese proprietary medicines. They collected 2080 samples of such medicines in Singapore and tested them for heavy metal content. Forty-two different medicines were found to contain metals in amounts exceeding the legal limits. Mercury was found in 28 products, lead in eight, arsenic in six and copper in one. One product contained both mercury and lead and another product contained both mercury and arsenic.” (Ernst, 2002).

Heavy metals can accumulate in the human body and may cause serious damage thus completely going against the point of tonic herbalism. It is best to seek out suppliers who do reliable transparent testing or grow far away from polluted areas. For example, Na’vi Organics provides lab results on request, this is from their website (https://www.naviorganics.uk/pages/our-sourcing-policy):

“In 2015, we were very fortunate to find a wonderful producer to work with in China. They have a very strict sourcing policy and a passionate in-depth knowledge of Traditional Chinese Medicine. After sampling their products and getting to know them, we were satisfied by their dedication to clean sourcing, high quality, and attention to detail during the processing involved. With this new partnership, we began to offer a select range of tonic herbs.

Since making a choice to stock some products that are produced in China, we understandably began to receive emails from customers expressing their concern regarding potential environmental pollutants. In response to this, all our products produced in China have Certificates of Analysis available on request”.

I can recommend reading Edzard Ernt’s review article listed below.

References

Ernst, Edzard. “Toxic heavy metals and undeclared drugs in Asian herbal medicines.” Trends in pharmacological sciences 23.3 (2002): 136-139.

Panax ginseng, the life root

Panax ginseng has held an important position in the traditional Chinese medicine (TCM) for a long time. In the first great Chinese herbal text, The Pen Tsao Ching, which was supposedly compiled by the emperor-sage Shen Nung around 3000 B.C. Shen Nung, he recommended ginseng for ‘enlightening the mind and increasing wisdom’, he also said, ‘continuous use leads to longevity’ (Castleman, 2001). Panax ginseng is known in TCM as a Qi tonic, that is known is boost the bodies overall energy and well-being. Not in a short-term stimulating way like caffeine, but in a more gentle building way over the longer term.

A scientific term for ginseng is ‘adaptogen’ which means a substance that increases resistance to non-specific stress, they are thought to have a balancing role to play on the body. Panax ginseng is thought to be useful for; normalizing immune function, chronic fatigue syndrome, boosting digestive power, male reproductive health, and longevity. One of the primary groups of bioactive molecules in ginseng are the ginsenosides and are thought to be capable of maintaining homeostasis and have anti-inflammatory, anti-oxidant, anti-apoptotic, and immune-stimulatory activities (Cho, 2012). It is a good adaptogen for supporting the immune system and nootropic to support concentration. I’ve noticed taking panax ginseng over a few months eliminated my seasonal allergy and improved my resistance to common colds so I did not get the cold I do every year at the same time. I did have to take it for a few months beforehand to build the immune system for the Winter.

There is an increasing body of scientific experiments, including well-controlled work on humans, that supports the use of panax ginseng as an useful medicinal herb. We can see from these 3 studies that panax ginseng affects the nervous and immune systems in humans.

Alzheimer disease: In a human study the authors found 4.5 grams of Korean white ginseng powder taken daily over 12 weeks improved cognitive parameters in Alzheimer disease patients significantly compared with a placebo (Lee, et al., 2008).

Chronic fatigue: A human study applied 1 or 2 grams of ethanol extract of Korean ginseng daily for 4 weeks (Kim et al., 2013). Serum levels of reactive oxygen species and malondialdehyde were lowered compared with the placebo (markers of oxidative stress). Symptoms of chronic fatigue were significantly lowered compared with the placebo.

Allergic rhinitis: Another human study examined whether 3 capsules 2 times (250 mg/capsule) of Korean red ginseng daily for 4 weeks reduced symptoms of allergic rhinitis, they found a significant effect was observed compared with the placebo (Jung et al., 2011).

Some herbalists will warn of panax ginseng being too stimulating or just for old people. I think this is an over generalization. Finding a good dose amount and timing is important. I take panax just in the morning and have found it a pleasant experience. Panax combines well with ashwagandha because it is calming and grounding. TCM superior tonic herbs it is often taken alongside include astragalus, he shou wu, and schizandra.

It is hard to obtain good quality panax ginseng as the roots must be at least six years old for the proper effects to manifest. I have used Korean red panax ginseng w/o artificial processing from 6-year-old roots and I was greatly impressed, surely it has earned its place as one of the worlds great tonic herbs. It is expensive, but I think it is often worth it.

Another point to make is there are other types of ginseng. For example, American ginseng is more calming, cooling, and moistening, but has many of the same benefits. As far as I am aware this is the only other type of ‘true’ ginseng. Again, sourcing good quality American ginseng may be difficult. There is also Siberian ginseng which isn’t in the same genus, but has similar effects.

Here are some properties of panax ginseng.

Actions: Qi tonic, adaptogen, nootropic, immune tonic, male aphrodisiac, anti-depressant

Specific indications include: Fatigue, cognitive problems, low sex drive, general weakness and debility, depression, weak appetite, pale, prone to colds and flu, weak immune system, allergies

Diseases: 
ADD/ADHD, Alzheimer’s, dementia, fibromyalgia, allergies, CFS, depression.

Energetics: Panax ginseng is warming and moistening.

Combinations: With ashwagandha to build energy and health. With St. John’s wort for mood.

Contra-indications: High BP. Do not use caffeine while taking panax.

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References

Castleman, Michael. “The new healing herbs.” Bantam Book, New York (2001): 465-471.

Cho, Ik-Hyun. “Effects of Panax ginseng in neurodegenerative diseases.” Journal of ginseng research 36.4 (2012): 342.

Kim, Hyeong-Geug, et al. “Antifatigue effects of Panax ginseng CA Meyer: a randomised, double-blind, placebo-controlled trial.” PLoS One 8.4 (2013): e61271.

Jung, Jae-Woo, et al. “Therapeutic effects of fermented red ginseng in allergic rhinitis: a randomized, double-blind, placebo-controlled study.” Allergy, asthma & immunology research 3.2 (2011): 103-110.

Lee, Soon-Tae, et al. “Panax ginseng enhances cognitive performance in Alzheimer disease.” Alzheimer Disease & Associated Disorders 22.3 (2008): 222-226.

Mixing adaptogens and nervines

This article is a brief guide to the adaptogens and nervines and how we could go about combining them. They are two powerful classes of herb useful for many problems. Although, it is better to use them after developing a good understanding of their traditional indications and contra indications.

It is thought adaptogens operate through gently modulating the sympatho-adrenal or hypothalamic-pituitary-adrenal axes of the endocrine system (Reviewed by Panossian, 2017), which are related to stress response, to adapt the organism to dealing with stress. These herbs are known as the Qi tonics or rasayana herbs in traditional Chinese or Ayurvedic medicine, respectively. They are called Qi tonics because they all have this characteristic of increasing a person’s overall energy or Qi. However, they are not simple stimulants like coffee, they also have a relaxing property to them which makes them so unique. Nervine herbs on the other hand, aside from the nervine stimulants, act to relax the nervous system to differing degrees. We may also define additional actions for nervines and adaptogens. For instance, the nervine American skullcap is also a nervine tonic and is thought to be effective for restoring normal sleep patterns. While the nervine lemon balm is also an effective carminative suited for reducing excessive digestive gas.

As well as herbal actions, adaptogens and nervines also have specific indications and affinities for different systems of the body. For example, astragalus and reishi are potent immune stimulators and so are suited for protecting against infections, while he shou wu and ashwagandha have an affinity for the male reproductive system and may improve sexual performance and drive. One common characteristic to adaptogens is they tend to be quite multi-purpose, like an herbal swiss army knife. Importantly, adaptogens and nervines also have different energetic properties, which relate to how warming, cooling, drying, or moistening they are on the individual’s constitution.

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(above) American skullcap, a nervine tonic and sedative. Best in a fresh tincture form.

Energetics

We have learnt from knowledge passed down through the generations that herbs, including adaptogens and nervines have certain energetic properties (i.e. warming, cooling, moistening, drying) (Figure 1). These should, ideally, be taken into account when selecting an adaptogen or nervine. A common finding, for example, if taking a drying herb like prickly ash, is that certain people who tend towards dryness (i.e. dry skin, constipation) tend to get dried out skin. This would be especially true for the vata constitution in Ayurveda (cold and dry). I observed this for the first time when testing prickly ash on myself, being a vata constitution dominantly, I was interested to see the skin almost immediately dry out and parts turn red on my hands after taking small doses of this potent herb (5-10 drops). Some time later, I also observed after taking a little too much ashwagandha, my hands dried out again. Ashwagandha is a drying and warming herb in Ayurveda.

Although some people still do not believe in herbal energetics, the same system of medicine based on heating, cooling, drying, or moistening herbs is found within ancient Greek, Ayurvedic, and traditional Chinese medicine. Perhaps, it is one of those things you must see for yourself first hand. David Winston provides more detailed information on energetics which are related to the taste of the herbs in his book, Adaptogens: herbs for strength, stamina, and stress relief (Winston, 2007).

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Figure 1. Energetic properties of common nervine and adaptogen medicinal herbs.

The nervous-endocrine system spectrum

Another way of viewing adaptogens and nervines is to examine how stimulating they are to the nervous system (Figure 2). Certain adaptogens, such as Asian ginseng tend to be more stimulating and may cause insomnia, while ashwagandha tends to be more calming and therefore potentially useful for sleep. It has been said young people are usually more suited to less stimulating adaptogens as they often have more energy or Qi, while for older people the converse applies. More stimulating adaptogens may be taken in the morning only if an individual finds them overly stimulating.

Adaptogens combine well with the nervine herbs because they may reinforce their relaxing activity and allow a more complex combination of herbal actions. For instance, combining a calming adaptogen such as ashwagandha with the nervine tonic, American skullcap, amplifies the calming activity of ashwagandha and creates a relaxing pair for the nervous system. This could be useful for those persons suffering with nervous over excitation like, insomnia and or anxiety.

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Figure 2. The nervous-endocrine system spectrum.

Formulation strategies

Typical considerations when choosing herbs for a formula that mixes adaptogens and nervines are; constitution (e.g. pitta, vata, kapha), diseased tissue state (e.g. hot (inflamed), cold, wet, dry, tense, relaxed), actions, affinities, and specific indications of the herb. It is also appropriate to consider when using an adaptogen that some people are more prone to insomnia and are very sensitive and so may respond better to a calming adaptogen such as ashwagandha or holy basil. Equally, some people may have a lot of dry skin going on and therefore a moistening nervine like hawthorn berry may be more appropriate. I recommend studying Matthew Wood’s The Earthwise Herbal books for a more complete explanation of constitutions and tissue states (Wood, 2009).

It also is important to read up on contra indications for herbs, these can be obtained from the herbal encyclopedia on this site or webMD or other sites and text books.

A simple way widely practiced is to just pick an herb by its action, e.g. nervine sedative. Although this can work well and there is room for a variety of different ways of deciding which herb to use, I think it is good to learn from the ancient traditions of the world such as Ayurveda and TCM.

Specific indications

We will now turn to examine some specific indications from traditional knowledge and (preliminary) scientific studies. These indications have been collected from traditional text books and scientific studies, they usually come from multiple independent sources. References for specific indications are included in the herbal encyclopedia. I have also tested many of these on myself and can therefore confirm many of the indications.

Adaptogens

Ashwagandha: Insomnia, anxiety, nerve pain, sexual/ reproductive problems, autoimmune diseases, fatigue, musculoskeletal conditions such as fibromyalgia and both types of arthritis, cognitive problems such as ADD, ADHD, and dementia.

Asian ginseng: Autoimmune diseases, allergies, fatigue, cognitive problems, sexual and reproductive problems in men, fibromyalgia, longevity.

Gotu kola: Anxiety, nerve pain, fatigue, rheumatoid arthritis, psoriasis, dry scaly skin, cognitive problems, autoimmune diseases, longevity.

Holy basil: Autoimmune diseases, nerve pain, anxiety, insomnia, boosting strength of the immune system, cognitive problems, allergies.

Rhodiola: Depression, fatigue, longevity, cognitive problems, recovery from brain injury.

He shou wu: Sexual weakness/debility in men, musculoskeletal conditions, constipation, inflammation of the GI tract, fatigue.

Schisandra: Anxiety, insomnia, fatigue, liver complaints and disorders, weak digestion, hypertension, palpitations, poor appetite.

Reishi: Anxiety, insomnia, fatigue, asthma, inflammation of GI tract, musculoskeletal conditions, weak immune system, allergies, cancer, longevity.

Licorice: Fatigue, inflammation of GI tract, dry cough, constipation.

Cordyceps: Asthma, autoimmune diseases, fatigue, sexual problems in men, weak immune system.

Astragalus: Weak immune system, fatigue, allergies, poor appetite.

Shatavari: Sexual problems in both sexes (but particularly women), fatigue, insomnia, inflammation of GI tract.

Nervines

St. John’s wort: Nerve pain, anxiety, depression, stabbing pains, muscle pains, shooting pains, nerve irritation.

American skullcap: Insomnia, anxiety, nerve pain, tense muscles, muscle pain.

Milky oat seed: Emotionally unstable, depression, insomnia, anxiety.

Blue vervain: Muscle tension, anxiety, insomnia, epilepsy.

Kava: More severe insomnia, anxiety, pain, muscle tension.

Lemon balm: Insomnia, anxiety, cognitive problems, excess digestive gas, depression.

California poppy: Nerve pain, chronic pain, insomnia, anxiety.

Valerian: Tense muscles, insomnia, anxiety.

Hawthorn: Hypertension, constipation, ADHD, dry skin.

Example adaptogen or adaptogen-nervine pairs

A nice way of working on a formula is thinking about pairs we might use. We could build on these to make a triplet, or just use a more simple pair, depending on need. All of the pairs below are geared towards tonifying and building ones health, energy, and well being. There is quite a lot of overlap in terms of effect, but ashwagandha is more calming and panax more energizing.

These are pairs I have personally tried together and liked. Note, panax ginseng is contra indicated with high BP and ashwagandha with hyper thyroidism and St. John’s wort has a few potential issues, best to read about St. John’s wort in more detail here.

Panax ginseng and ashwagandha: Will increase depleted energy levels and vitality long term. Should have a positive impact on emotions and anxiety. Ashwagandha is good for muscleoskeletal and nervous system inflammation and pain. Will increase male sex drive. Ginseng should boost appetite and boost immune health as a preventative medicine. 6-year-old roots of Korean red ginseng are recommended and KSM-66 ashwagandha is a nice choice. This is pretty energetically balanced in terms of dryness and moisture, but towards the warming side.

Ashwagandha and St. John’s wort: A strong Indian-Western nerve tonic pair, suitable for neuropathic pain, muscleoskeletal inflammation, lowering anxiety, and improving the emotional state. Will increase energy more gently than by using panax ginseng. St. John’s wort should be used in a fresh as possible tincture from the fresh flowers.

Ashwagandha and American skullcap: This pair is well suited to anxiety and insomnia and have good anxiolytic synergy together. Does not cause daytime sleepiness. May be tried for nervous system damage and pain. Ashwagandha is good for muscleoskeletal pain and inflammation.

An example of mixing adaptogens and nervines

You can do a lot with nervines and adaptogens.  This is just an example of what we might consider when formulating. Tissue state is NA because the nervous system does not have wet, cold, dry, and hot states in the same way the joints or lungs do, for example.

St. John’s wort, skullcap, and ashwagandha are some of the best tonics for vata, they are only slightly drying, and are calming, and restorative. Particularly skullcap and ashwagandha are good for sleep. Although as previously mentioned, too much ashwagandha will dry out vata type people especially. Vata is symbolic of the wind element in Ayurveda with a tendency to change, these people may be hypermobile, thin, prone to anxiety and insomnia, dryness, weak digestion, and pale skin.

The addition of the moistening nervine, hawthorn berry, which I find effective in preventing dryness, means the below formula is suitable for vata dominant types or people prone to dryness.

In terms of actions, we have a strong nervine tonic element to the formula with St. John’s wort and ashwagandha.

Constitution: Dry cold/hot. Vata-pitta.
Condition/s: Tingling pains, insomnia. Vata aggravation.
Tissue state/s: NA
Systems/: Nervous system
Action/s: Nervine tonic, adaptogen, analgesic, nootropic, sedative, antidepressant
Energetics: St. John’s wort (warming, drying), ashwagandha (warming, drying), hawthorn berry (cooling, moistening)
Contraindications: Any pharmaceutical drugs, especially SSRIs because of St. John’s wort. High BP because of panax ginseng. Ashwagandha is contra indicated with hyper thyroid.

Summary

There is, unfortunately, a lack of scientific knowledge surrounding the medicinal properties of plants compared with mainstream drugs, however, what we do have is some strong traditional knowledge. I think it is best to research over multiple traditional sources when deciding to test a medicinal plant on yourself or others. If there are many different herbalists seemingly independently suggesting a plant is good for something, this is of course a good sign.

It is important to remember that herbs may interact with drugs, sometimes in a dangerous manner so this must be properly researched or a doctor consulted. However, sometimes herbs may help get a person off drugs, so it may work both ways. In my own practice, I have been able to safely remove myself from the drug, lyrica, using herbs like American skullcap and ashwagandha. Some medicinal herbs have specific contra indications like panax ginseng and high blood pressure, that are good to know about. However, as for the herbs described on this site, the truth is they are safer than drugs when used correctly. It is a widespread misbelief they are dangerous or ineffective.

Herbalism of different varieties is being more widely practised by folk herbalists, including bio-hackers, who will use just about anything and are very keen on scientific studies while they often shun traditional knowledge. I think what is needed is a more balanced approach drawing from the great herbal teachers of the world as well as any scientific developments. After all science will always have an incomplete understanding of medicinal herbs, it is up to the herbalists to experiment to find new specific indications and formula.

Further reading

David Winston: https://www.herbalstudies.net/_media/resources/library/HarmonyRemedies(1).pdf

Cautions and contraindications

Using adaptogens for energy instead of good sleep, lifestyle, and eating habits will lead to a sleep debt and burnout. Stimulating adaptogens may be best taken in the morning to avoid insomnia. We recommend reading this PDF by Paul Bergner, an herbalist highly experienced with using the adaptogens if you are thinking of using them on yourself or on others (link).

References

Panossian, Alexander. “Understanding adaptogenic activity: specificity of the pharmacological action of adaptogens and other phytochemicals.” Annals of the New York Academy of Sciences (2017).

Winston, David, and Steven Maimes. Adaptogens: herbs for strength, stamina, and stress relief. Inner Traditions/Bear & Co, 2007.

Groves, Maria. Body into Balance. Storey Publishing, 2016.

Wood, Matthew. The Earthwise Herbal: A Complete Guide to New World Medicinal Plants. North Atlantic Books, 2009.

Ashwagandha, an Indian ginseng

Ashwagandha is one of the most well known and universally praised plant medicines and has been used in Ayurveda or traditional Indian medicine for at least 3000 years (Castleman, 2001). In the Charaka Samhita it is recommended as a whole-body tonic, particularly for emancipation, reproductive ability, and longevity.

In Ayurveda, it is classified as a rasayana or rejuvenator herb otherwise known as adaptogen in Western science, or Qi tonic in traditional Chinese medicine. While Qi tonics may all be quite different in a way, they have the joint property of activating or stimulating the nervous system while still relaxing. It is thought this is because their modulation of the human stress response system, somehow gently priming it to balance stress hormones such as cortisol, relax, and energise (Reviewed by Panossian, 2017). These tonics can help reduce fatigue and contribute to overall well being. I believe ashwagandhas medicinal properties extend far beyond one pathway and molecular target and there is now increasing evidence to support its broad medicinal properties in humans. We can see just from these human studies it has likely anti-inflammatory properties (as can help osteoarthritis), anxiolytic properties (helps anxiety), stamina boosting properties (helps fatigue), and modulates hormones of the body (relieves mild thyroid failure).

Anxiety: One study (n = 64, double blind placebo controlled) found that with treatment of 300 mg extract of ashwagandha root twice daily reduced stress significantly versus a placebo (Chandrasekhar et al., 2012). Adverse events were mild and similar to the placebo.

Osteoarthritis: A study (n=60, double blind placebo controlled) on patients with osteoarthritis knee pain found that either 250mg or 125mg of ashwagandha per day over 12 weeks found a significant reduction in pain in either group, with the 250mg treatment resulting in a stronger effect (Ramakanth et al., 2016).

Mild thyroid failure: Another study (n=50, double blind placebo controlled) found patients who took 600mg ashwagandha daily for mild thyroid failure (subclinical hypothyroidism) significantly normalised their thyroid indices (Sharma et al., 2017).

Fatigue: One study (n = 100, open label, placebo controlled) observed significant improvements in fatigue in breast cancer patients taking ashwagandha (Biswal et al., 2013).

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Why ashwagandha is particularly special among the adaptogens, in my view, is because it is so gentle and relaxing for the whole nervous system. Dosage may be adjusted to the level even in sensitive persons such as myself it actually helps sleep, by calming the nerves, but also provides that gentle calm energy that I think is conductive to the healing process. Whilst it is a fairly strong anti-convulsant and anxiolytic similar to lyrica, I have found withdrawal from ashwagandha does not cause a withdrawal like lyrica does. Quite why we continue to take mainstream anti-anxiety medications on mass, well, I will leave you to figure that out.

Ashwagandha is quite suited to treating vata aggravations (often nervous system imbalances), while having an anti-inflammatory nature suited to treating certain autoimmune conditions. This includes a variety of types of chronic pain conditions especially muscleoskeletal or neurological diseases. Expect to see an increasing level of scientific support for ashwagandha in coming years, but the truth is: ashwagandha is a powerful and gentle healing herb for a range of conditions.

Ashwagandha_(Marathi-_अश्वगंधा)_(21601754599).jpg

Actions: Rasayana, adaptogen, nervine tonic, nootropic, immune tonic, antirheumatic, aphrodisiac

Specific indications include: Joint or muscle pains and aches, fatigue, red hot inflamed joints or skin, anxiety, cognitive problems, low sex drive

Example diseases: 
Osteoarthritis, ADD/ADHD, Alzheimer’s, dementia, rheumatoid arthritis, fibromyalgia, stress linked hypertension

Energetics: Ashwagandha is warming and slightly dry. Ashwagandha balances vata and kapha, in excess, because of its heating nature it can imbalance pitta. It is also important to watch out for excess dryness if taking ashwagandha.

Form: I prefer KSM-66 overall. KSM-66 is more energising, the traditional root powder is better for sleep.

Dose: Between 1-4 300mg capsules of KSM66 may be used per day. For a tincture, an approximate dose is 10-60 drops, 2-3 times daily.

Contraindications: It is best to avoid ashwagandha if you have hyperthyroidism as it stimulates the thyroid. It also should be used with caution if combining with sedative medication as may interact unfavourably or enhance effects of these. It may cause GI distress on occasion.

Combines well with: Fresh skullcap tincture for a worn out depleted nervous system with insomnia, fatigue, and anxiety. With a fresh St. John’s wort tincture for nerve pain. Alongside gotu kola and calamus root to treat nerve damage. With gotu kola and sarsaparilla for treating inflammatory arthritis.

 

References

Biswal, Biswa Mohan, et al. “Effect of Withania somnifera (Ashwagandha) on the development of chemotherapy-induced fatigue and quality of life in breast cancer patients.” Integrative cancer therapies 12.4 (2013): 312-322.

Castleman, Michael. “The new healing herbs.” Bantam Book, New York (2001): 465-471.

Chandrasekhar, K., Jyoti Kapoor, and Sridhar Anishetty. “A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full-spectrum extract of ashwagandha root in reducing stress and anxiety in adults.” Indian Journal of Psychological Medicine 34.3 (2012): 255.

Gardner, Tanya, and A. H. P. Level. “The Characteristics, Benefits and Application of Ashwagandha in the West.” Image 2 (2015): 2.

Panossian, Alexander. “Understanding adaptogenic activity: specificity of the pharmacological action of adaptogens and other phytochemicals.” Annals of the New York Academy of Sciences (2017).

Ramakanth, G. S. H., et al. “A randomized, double blind placebo controlled study of efficacy and tolerability of Withaina somnifera extracts in knee joint pain.” Journal of Ayurveda and integrative medicine 7.3 (2016): 151-157.

Sharma, Ashok Kumar, Indraneel Basu, and Siddarth Singh. “Efficacy and Safety of Ashwagandha Root Extract in Subclinical Hypothyroid Patients: A Double-Blind, Randomized Placebo-Controlled Trial.” The Journal of Alternative and Complementary Medicine (2017).

What is an adaptogen herb?

In the Soviet Union in the mid-1950s adaptogens were defined by Nikolai Vasilievich Lazarev as harmless substances that can increase resistance to non-specific stress. Adaptogenic herbs are known as either ‘rasayana’ or ‘Qi tonic’ herbs in Ayurvedic and Chinese medicine, respectively. Although every adaptogen is often very different from one another and suited to different people, they are used by herbalists to treat a wide array of disorders, including fatigue, stress, immune, sexual, or nervous system problems, and depression (Winston, 2007). A popular current theory that may explain their broad applicability is that these herbs primarily modulate the sympatho-adrenal or hypothalamic-pituitary-adrenal axes of the endocrine system to adapt the organism to dealing with short or long-term stress (Panossian, 2017). Hormones such as cortisol are modulated in level by adaptogens and have receptors on both immune and nerve cells.

Recent molecular studies demonstrate adaptogen treatment can be considered to have a vaccination type effect on these stress response system. For example, it has been shown in C. elegans that adaptogens can induce translocation of the DAF-16 transcription factor from the cytoplasm into the nucleus, favouring an increased synthesis of proteins involved in stress resistance (Wiegant et al., 2009). Research on the ADAPT-252 compound (rhodiola, schisandra, eleutherococcus) shows that adaptogens can increase the synthesis of the heat shock protein HSP70 in vivo, a mediator of the adaptive stress response (Hernández‐Santana et al., 2014). The compromised ability of neurons to express HSP70 is associated with aging-related neurodegeneration and HSP70 application has been found to extend lifespan of animals and improve memory. This article describes in more detail the biology, history, and science surrounding the adaptogenic herbs. First we will need to delve into some terminology.

Figure 1. The adaptogen herbs eleutherococcus, schisandra, and rhodiola (from left to right).

Core terminology

Endocrine system:
The endocrine system is the series of glands that release hormones into the blood to be carried to distant target organs. The major endocrine glands include; the pineal gland, the pituitary gland, pancreas, ovaries, testes, the thyroid gland, the parathyroid gland, and the adrenal glands.

The adrenal cortex: The adrenal cortex is the outer part of the adrenal gland and produces hormones such as cortisol and aldosterone.

Hypothalamus: The hypothalamus is a region of the brain containing small nuclei with a variety of functions, one of the most important of these is to link the nervous system with the endocrine system via the pituitary gland.

Pituitary: The pituitary or ‘master’ gland is a pea-sized structure found at the base of the brain immediately below the hypothalamus, to which it is attached via nerve fibres. It produces important hormones such as adrenocorticotropic hormone, growth hormone, thyroid stimulating hormone.

Hypothalamic-pituitary-adrenal (HPA) axis: The HPA axis comprises of 3 organs and their direct interactions, namely, the hypothalamus, the pituitary gland, and the adrenal glands. It is a major neuroendocrine system that controls reactions to stress and regulates many processes, including digestion, the immune system, mood and emotions, sexuality, and energy storage and expenditure.

Sympatho-adrenal-system (SAS): The SAS is a physiological connection between the sympathetic nervous system and the adrenal medulla and is important in the bodies response to outside stimuli. The SAS plays an important role in maintaining glucose levels, blood pressure, and other metabolic pathways that couple with bodily responses to the outside environment.

Cortisol: Cortisol is a steroid hormone that is produced by the adrenal glands which sit on top of each kidney. When released into the bloodstream it then acts on many different parts of the body and helps the body respond to stress, increases metabolism of glucose, controls blood pressure, and reduce inflammation.

Adrenocorticotrophic hormone-releasing factor (CRF): CRF is released by the paraventricular nucleus of the hypothalamus in response to stress. Its primary function is the stimulation of the pituitary synthesis of ACTH, as part of the HPA axis.

Vasopressin (AVP): AVP is a hormone synthesized in the hypothalamus and is released into the circulation. It plays a key role in maintaining osmolality (the concentration of dissolved particles, such as salts and glucose, in the serum).

Adrenocorticotrophic hormone (ACTH): ACTH is produced by the pituitary gland and its primary function is to stimulate the production and release of cortisol from the adrenal gland cortex.

Adrenaline: Adrenaline is a hormone released from the adrenal glands, together with noradrenaline, its primary role is to prepare the body for fight or flight.

Corticosteroids: Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates. Glucocorticoids are a class of corticosteroids of which cortisol is one. There are also synthetic analogues of these hormones.

Nitric oxide (NO): NO is a key regulator and mediator of numerous processes in the nervous, immune, and cardiovascular systems. For instance, it stimulates vascular smooth muscle relaxation resulting in arterial vasodilation and increasing blood flow.

Heat shock proteins: Heat shock proteins are a family of proteins that are made by cells in response to stress. They chaperone other proteins, guarding them from folding improperly, going astray, or misassembling while forming larger protein aggregates.

HPA axis biology and its dysregulation in disease

HPA axis activity is modulated by CRF and AVP which are secreted from the hypothalamus (Figure 2). These activate the secretion of ACTH from the pituitary which then activates the secretion of the glucocorticoids (or cortisol in humans) from the adrenal cortex (Pariante et al., 2008). Glucocorticoids interact with receptors in various tissues including back at the HPA axis, which is a classic feedback inhibition loop. In this loop, glucocorticoids inhibit both CRF and AVP from the hypothalamus and ACTH from the pituitary. Although still quite poorly understood, cortisol alters the function of the immune system and influences both macrophages and lymphocytes (Padgett, 2003). Both these types of cell are directly responsive to cortisol through the glucocorticoid receptor that they express. This provides a direct link between stress and the immune system.

figure1.png

Figure 2. The influence of stress upon the HPA axis.

The strong anti-inflammatory effects of synthetic glucocorticoids (steroids) in drug therapy are similar to the effects of endogenous glucocorticoids released via the adrenal cortex (Morand, 2001). Defects in HPA axis function are implicated in animal models of rheumatoid arthritis and are hypothesised to contribute towards the disease. Manipulation of HPA axis-driven endogenous anti-inflammatory responses may provide a method for the therapeutic manipulation of inflammatory diseases.

As well as the immune system, glucocorticoids are also known to regulate neuronal survival, neurogenesis, the sizes of complex structures (e.g. the hippocampus), and emotions (Pariante et al., 2008). Reflecting on the HPA axis and its link between stress and the nervous system we are unsurprised to find that it has been found dysregulated in psychiatric disorders, particularly in major or melancholic depression. A significant percentage of depressed patients have increased levels of cortisol in the saliva, plasma, urine, and increased size and activity of the pituitary and adrenal glands. Evidence from clinical studies suggests that childhood trauma is associated with sensitisation of the neuroendocrine stress response, glucocorticoid resistance, increased CRF activity, immune activation, and reduced hippocampal volume (Heim et al., 2008). These neuroendocrine features mirror those found in cases of major depression. The diseases where a dysregulated HPA axis is thought to occur are listed below in Table I.

Table I: Diseases associated with suppression or activation of immune-mediated inflammation through defects in the HPA axis or its target tissues (adapted from Chrousos, 1995)
Suppression of immune meditated inflammatory reactions Activation of immune meditated inflammatory reactions
 
Increased HPA-axis activity Decreased HPA-axis activity
Melancholic (major) depression Rheumatoid arthritis
Chronic stress Adrenal insufficiency
Chronic alcoholism Seasonal or atypical depression
  Hypothyroidism
  Chronic fatigue or fibromyalgia
 
  Resistance to glucocorticoids
  Rheumatoid arthritis
  Steroid resistant asthma
  Systemic lupus erythematosus


The history of adaptogens

In the late 1940s, scientists of the Far Eastern Division of the Soviet Academy of Sciences in Vladivostok, Siberia, started to study herbs that caused a state of ‘non-specifically increased resistance’ of an organism using animal models and humans (Davydov and Krikorian, 2000). Later, Dr Nikolai Vasilievich Lazarev (1895-1974) a then leading figure in Soviet pharmacology proposed to the scientific community in the mid-1950s that herbs or other substances which could bring about an increased non-specific resistance to stress be called ‘adaptogens’. In the Soviet literature of the time other terminology to describe adaptogenic herbs included, ‘revitalizing therapies’, ‘tonic herbs’, and ‘immunomodulatory substances’. The properties of these adaptogens were outlined in a publication by Brekhman in the 1960s (Brekhman, 1968) as follows:

  1. The action of an adaptogen should be innocuous and cause minimal disturbance to the normal physiological functions of an organism. It must be absolutely harmless.
  2. An adaptogenic agent should not be active only in a specific context or against a particular background. It must have a broad therapeutic spectrum of action.
  3. The action of an adaptogen has to be non-specific, and so resistance to a wide variety of action of harmful factors, whether of a physical, chemical, or biological nature, has to increase.
  4. An adaptogen has to have a normalising or stabilising action independent of the direction of previous changes.

This somewhat vague definition is not widely known or accepted by mainstream medicine and has been subject to scrutiny for lack of precision (Davydov and Krikorian, 2000). However, the term adaptogen has been refined and defended in work by Alexander Panossian and his colleges (Panossian et al., 2005; Panossian, 2017; Panossian et al., 1999).

Mechanism of action of the adaptogens

It has been proposed, based on animal and human studies, that the action of adaptogens in a single dose is useful in situations that require a rapid response to stress (e.g. heavy exercise) and is related with the modulation by adaptogens of the SAS (Panossian et al., 2005). The SAS provides a rapid response to a stressor and results in increased levels of ATP, NO, cortisol, and various neuropeptides. A characteristic behaviour of adaptogens is that they act as eustressors (or good stressors) and as mild stress mimetics that induce stress-protective responses (Panossian, 2017). Adaptogen treatment can be considered to have a vaccination type effect on the stress response system. For example, in humans, compared with a placebo the adaptogen schisandra increases NO and cortisol in blood plasma and saliva prior to physical exercise, in a similar manner to what normally happens during physical exercise (Panossian et al., 1999). Then, after exercise, in the adaptogen treatment group there are no further increases in NO and cortisol which is related to the enhancement of ordinary physical performance. In addition, it has been observed in C. elegans that adaptogens induce translocation of the DAF-16 transcription factor from the cytoplasm into the nucleus, favouring an increased synthesis of proteins involved in stress resistance and longevity (Wiegant et al., 2009). In this study, it was similarly concluded to the human study, adaptogens are experienced as mild stressors which promote increased stress resistance and, at least in C. elegans, a longer lifespan.

The repeated action of adaptogens on chronic illness is related with the modulation by adaptogens of the HPA axis, which plays a role in the reaction and adaptation to repeated stress (Panossian et al., 2005). To recap, stress triggers secretion of CRF from the hypothalamus, followed by the secretion of ACTH from the pituitary, this stimulates the release of adrenal hormones and NPY to help cope with the stress. Feedback inhibition is initiated by cortisol secreted from the adrenal cortex, which binds to the glucocorticoid receptors (GR) in the brain. This inhibitory signal stops the stress induced release of cortisol and thus cortisol decreases to normal levels in the blood. However, in depression, this feedback inhibition of cortisol via the GR appears blocked and cortisol content in the blood of depressive patients is chronically high (Jovicic et al., 2015). This phenomenon is associated with impaired memory and ability to concentrate, fatigue, and other problems. It is known that the GR are phosphorylated by an enzyme called JNK and this is associated with increased glucocorticoid resistance, increased phosphorylation of GR is observed in patients with depression. Adaptogens stimulate the formation of HSP70 which suppresses elevated JNK and cortisol in the stress response (Panossian, 2017). Thus, adaptogens may help restore a blocked feedback inhibition of the stress response in depressive patients.

Central players modulated by plant adaptogens (such as rhodiola, eleutherococcus, schisandra, ginseng, withania) include the stress hormones cortisol and neuropeptide Y (NPY) and several important mediators of the adaptive stress response (such as NO, stress-activated protein kinases, heat shock proteins (HSP70 and HSP25), and the FOXO transcription factor) (Panossian, 2017). Using experimental models, it has been demonstrated the compromised ability of neurons to express HSP70 is associated with aging-related neurodegeneration (Bobkova et al., 2015). HSP70 treatment has been found to extend lifespan of animals and improve learning and memory, increase curiosity, decrease anxiety, and help preserve synaptic structures that are known to degrade with age. Other studies imply reduced ability to express HSP70 in response to stress may be a common event underlying the aging process (Heydari et al., 1994). Therefore, HSP70 is a candidate pharmacological target of antiaging therapies (Panossian, 2017), although, synthetic chemicals used to induce HSP70 are cytotoxic and are unsafe. However, plant adaptogens have been used safely over a wide dose range (including up to 3000 mg/kg of rat body weight) even with repeated long-term administration (months). The individual plant adaptogens rhodiola, schisandra, eleutherococcus, and their formulation as ADAPT-232, stimulates the expression of HSF-1 and HSP72 in ex vivo neuroglia, provokes HSP72 release from cells, and increases expression of HSP70 in vivo (Panossian et al., 2009; Chiu et al., 2004; Hernández‐Santana et al., 2014; Lee et al., 2009; Li et al., 2014). Of these studies, for example, it was observed continued intake of rhodiola root extract significantly reduced swimming fatigue by increasing glycogen levels, boosted energy generated by lipogenic enzymes, and significantly upregulated HSP70 mRNA (Hernández‐Santana et al., 2014).

Further work on the adaptogen formula, ADAPT-232, has found it promotes expression and release of HSP72 from glioma cells and this requires the action of HSF1 or NPY (Panossian et al., 2012). HSF1 and NPY are likely primary upstream molecular targets of adaptogens in neuroglia. ADAPT-232 appears to act on NPY expression through the upregulation of HSF-1, which lies upstream of HSP72 expression and release. Additionally, ADAPT-232 upregulates both HSP70 and NPY ex vivo (Asea et al., 2013). The activation of NPY by ADAPT-232 promotes HSP70 expression in neuroglia, which helps to maintain homeostasis. It is thought that the induction and release of stress-induced hormone NPY and the stress-induced chaperone HSP70 into circulation is an innate defence response to mild stress and this increases tolerance, adaption, and may also confer longevity (Panossian, 2017). This pathway promotes adaptive and stress-protective effects via varying molecular components throughout the central nervous, sympathetic, endocrine, immune, cardiovascular, and gastrointestinal systems.

Figure 3. More adaptogen herbs. Asian ginseng, rhodiola, and withania (ashwagandha) (from left to right).

It has been demonstrated rhodiola, schisandra, eleutherococcus, withania, and ginseng extend the life span of the nematode C. elegans when stressed (Wiegant et al., 2009; Lee et al., 2007; Kumar et al., 2013), the fruit fly (D. melanogaster) (Jafari, 2007), and the yeast S. cerevisiae (Bayliak et al., 2011). An age-related decline in the ability to induce HSP70 was found in nervous system tissue, (Sherman et al., 2001; Winklhofer et al., 2008) in skeletal and cardiac muscle, and in the liver (Gagliano et al., 2007). It is also noteworthy, inhibition of HSF1 and HSP70 expression occurs in Alzheimer’s disease and is associated with the accumulation of plaques of aggregated β-amyloid peptide (Bhat et al., 2004). Also, it is the heat shock proteins that protect liver cells from the toxic effects of alcohol, heavy metals, xenobiotics, and oxidants. It is known the age-related decline of HSP70 expression contributes to the reduced efficacy of liver detoxification function in aged individuals (Gagliano et al., 2007). A 4-month study in 2-year-old rats showed that, in comparison with a control group, the ADAPT-232 group demonstrated higher liver detoxifying function, better CNS function (memory and learning ability), no development of cardiac insufficiency and hypercholesterolemia, less stress sensitivity, no impaired apoptosis, and no spontaneous tumour promotion (Makarov et al., 2007).

Conclusions

Recent work on the adaptogens in experimental systems has given new insights into the molecular basis on their action on stress response. While no single pathway is responsible for their action, new targets include the heat shock proteins (e.g. HSP70), NPY, and HSF-1. The increase by adaptogens of HSP70 is an interesting discovery since traditionally they have been viewed as life span increasing and this protein is a target of modern longevity research. As discussed in this article, in various experimental (non-human) systems, adaptogens and adaptogenic formula result in increased life expectancy under stressful conditions. It will be interesting to determine whether the same pathways that are involved in this phenomenon in models are also activated in humans with adaptogen treatment. The next part in this article series will be on the adaptogen materia medica and their traditional indications.

For further information regarding the recent scientific developments surrounding the adaptogens, a recent review by Alexander Panossian has been the source of much of the information contained in this article (Panossian, 2017). For more traditional insights into the adaptogenic herbs there is David Winston’s book entitled, ‘Adaptogens: Herbs for Strength, Stamina, and Stress Relief’ (Winston, 2007).

Cautions and contraindications

Whilst adaptogens are potentially useful medicines and foods, they can cause insomnia and over stimulation in some individuals (especially the more stimulating ones; e.g. rhodiola, schisandra, Asian ginseng) and depending on them for energy instead of good sleep and eating habits will lead to a ‘sleep debt’ and eventual burnout. It is also sensible to consider the energetic properties of each adaptogen. For instance, schisandra is a drying adaptogen and in a person prone to dryness (e.g. dry skin and slow bowel habits), it may well aggravate this tendency in the longer term. It is best to study the traditional use of the adaptogenic herbs alongside any scientific papers. I recommend reading this PDF by Paul Bergner, an herbalist highly experienced with using the adaptogens if you are thinking of using them on yourself or on others (link).

References

Asea, Alexzander, et al. “Evaluation of molecular chaperons Hsp72 and neuropeptide Y as characteristic markers of adaptogenic activity of plant extracts.” Phytomedicine 20.14 (2013): 1323-1329.

Bayliak, Maria M., and Volodymyr I. Lushchak. “The golden root, Rhodiola rosea, prolongs lifespan but decreases oxidative stress resistance in yeast Saccharomyces cerevisiae.” Phytomedicine 18.14 (2011): 1262-1268.

Bhat, Ratan V., Samantha L. Budd Haeberlein, and Jesús Avila. “Glycogen synthase kinase 3: a drug target for CNS therapies.” Journal of neurochemistry 89.6 (2004): 1313-1317.

Bobkova, Natalia V., et al. “Exogenous Hsp70 delays senescence and improves cognitive function in aging mice.” Proceedings of the National Academy of Sciences 112.52 (2015): 16006-16011.

Brekhman, I. Eleutherokokk (Eleutherococcus). Nauka Publishing House, Leningrad, USSR in Russian. (1968)

Chiu, Po Yee, and Kam Ming Ko. “Schisandrin B protects myocardial ischemia-reperfusion injury partly by inducing Hsp25 and Hsp70 expression in rats.” Molecular and cellular biochemistry 266.1 (2004): 139-144.

Chrousos, George P. “The hypothalamic–pituitary–adrenal axis and immune-mediated inflammation.” New England Journal of Medicine 332.20 (1995): 1351-1363.

Davydov, Marina, and A. D. Krikorian. “Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. (Araliaceae) as an adaptogen: a closer look.” Journal of ethnopharmacology 72.3 (2000): 345-393.

Gagliano, Nicoletta, Fabio Grizzi, and Giorgio Annoni. “Mechanisms of aging and liver functions.” Digestive diseases 25.2 (2007): 118-123.

Heim, Christine, et al. “The link between childhood trauma and depression: insights from HPA axis studies in humans.” Psychoneuroendocrinology 33.6 (2008): 693-710.

Hernández‐Santana, Aaron, et al. “A Rhodiola rosea root extract protects skeletal muscle cells against chemically induced oxidative stress by modulating heat shock protein 70 (HSP70) expression.” Phytotherapy research 28.4 (2014): 623-628.

Heydari, A. R., et al. “Hsp70 and aging.” Cellular and Molecular Life Sciences 50.11 (1994): 1092-1098.

Jafari, Mahtab, et al. “Rhodiola: a promising anti-aging Chinese herb.” Rejuvenation research 10.4 (2007): 587-602.

Jovicic, Milica J., et al. “Modulation of c-Jun N-terminal kinase signaling and specific glucocorticoid receptor phosphorylation in the treatment of major depression.” Medical hypotheses 85.3 (2015): 291-294.

Kumar, Ranjeet, et al. “Withania somnifera root extract extends lifespan of Caenorhabditis elegans.” Annals of neurosciences 20.1 (2013): 13.

Lee, Fang-Tsai, et al. “Chronic Rhodiola rosea extract supplementation enforces exhaustive swimming tolerance.” The American journal of Chinese medicine 37.03 (2009): 557-572.

Lee, Joon-Hee, et al. “Effects of ginsenosides, active ingredients of Panax ginseng, on development, growth, and life span of Caenorhabditis elegans.” Biological and Pharmaceutical Bulletin 30.11 (2007): 2126-2134.

Li, Libo, et al. “Schisandrin B attenuates acetaminophen‐induced hepatic injury through heat‐shock protein 27 and 70 in mice.” Journal of gastroenterology and hepatology 29.3 (2014): 640-647.

Makarov, V. G., et al. “Potential use of plant adaptogen in age related disorders, celebration of the centennial birth of Hans Selye, Budapest, Hungary.” Cell Stress Chaperones 242 (2007).

Morand, Eric F., and Michelle Leech. “Hypothalamic–pituitary–adrenal axis regulation of inflammation in rheumatoid arthritis.” Immunology and cell biology 79.4 (2001): 395-399.

Padgett, David A., and Ronald Glaser. “How stress influences the immune response.” Trends in immunology 24.8 (2003): 444-448.

Panossian, A. G., et al. “Effects of heavy physical exercise and adaptogens on nitric oxide content in human saliva.” Phytomedicine 6.1 (1999): 17-26.

Panossian, Alexander, and H. Wagner. “Stimulating effect of adaptogens: an overview with particular reference to their efficacy following single dose administration.” Phytotherapy Research 19.10 (2005): 819-838.

Panossian, Alexander, et al. “Adaptogens exert a stress-protective effect by modulation of expression of molecular chaperones.” Phytomedicine 16.6 (2009): 617-622.

Panossian, Alexander, et al. “Adaptogens stimulate neuropeptide Y and Hsp72 expression and release in neuroglia cells.” Frontiers in neuroscience 6 (2012).

Panossian, Alexander, et al. “Synergy and antagonism of active constituents of ADAPT-232 on transcriptional level of metabolic regulation of isolated neuroglial cells.” Frontiers in neuroscience 7 (2013).

Panossian, Alexander, Patricia L. Gerbarg, and George Canguilhem. “Potential use of plant adaptogens in age-related disorders.” Complementary and Integrative Therapies for Mental Health and Aging (2015): 197.

Panossian, Alexander. “Understanding adaptogenic activity: specificity of the pharmacological action of adaptogens and other phytochemicals.” Annals of the New York Academy of Sciences (2017).

Pariante, Carmine M., and Stafford L. Lightman. “The HPA axis in major depression: classical theories and new developments.” Trends in neurosciences 31.9 (2008): 464-468.

Sherman, Michael Y., and Alfred L. Goldberg. “Cellular defenses against unfolded proteins: a cell biologist thinks about neurodegenerative diseases.” Neuron 29.1 (2001): 15-32.

Wiegant, F. A. C., et al. “Plant adaptogens increase lifespan and stress resistance in C. elegans.” Biogerontology 10.1 (2009): 27-42.

Winklhofer, Konstanze F., Jörg Tatzelt, and Christian Haass. “The two faces of protein misfolding: gain‐and loss‐of‐function in neurodegenerative diseases.” The EMBO journal 27.2 (2008): 336-349.

Winston, David, and Steven Maimes. Adaptogens: herbs for strength, stamina, and stress relief. Inner Traditions/Bear & Co, 2007.

Why rasayana herbs are so important

Traditional Indian medicine or Ayurveda is ancient and dates back approximately 7000 years (Puri, 2003). Ayurveda has 8 different divisions which divide medicinal plants dependent on their actions. An important one is called the ‘rasayana tantra’. The word, ‘rasayana’, literally means the path that ‘rasa’ goes along (Rege et al., 1999). Where ‘rasa’ means ‘the primordial plasma’ and ‘ayana’ means ‘path’. In Ayurveda, the qualities of the rasa-dhatu (‘primary waters of the body’) influence the health of other ‘dhatus’ otherwise known as ‘tissues’ of the body. Therefore, any medicine that improves the quality of rasa should strengthen the well-being of all other tissues in the body. These are the rasayana medicines and are said to possess the powerful abilities of restoring youth, conferring longevity, and preventing and alleviating disease (Puri, 2003).

Rasayana herbs include the following; Amla, Arjuana bark, ashwagandha, bacopa, bala, bhringaraj, gotu kola, guduchi, holy basil, hoppea, shatavari, shilajit, and turmeric (Winston, 2007). These herbs can be taken for long durations without causing side effects, and in fact, indicated for longevity by the traditional cultures they were part of. Interestingly, these characteristics are shared with the ‘superior tonics’ in traditional Chinese medicine. I will now provide a summary of four of my favorite rasayana herbs from Ayurvedic medicine.

Ashwagandha

Withania_somnifera_wikicomoons

Ashwagandha is a small shrub and member of the nightshade family. The name, ‘ashwagandha’, can be translated as meaning ‘smells like a stallion’, and this refers to the smell of the root and the belief it bestows on the individual the strength of a stallion (Gardner et al., 2015). Scientific studies using experimental models have shown ashwagandha has numerous medicinal properties such as; anti-inflammatory (Chandra et al., 2012), anti-oxidant (Bhattacharya et al., 2001), neuroprotective (Kurapati et al., 2003), neuroregenerative (Nakayama et al., 2007), and anti-tumour effects (Widodo et al., 2007). There are a few human clinical trials of reasonable quality. For instance, one study found ashwagandha extract (300 mg root twice daily) reduced stress significantly versus a placebo in a study of 64 people. In another study, this time examining osteoarthritis, ashwagandha was applied in a formula as it often is in Ayurvedic medicine. The authors applied it alongside turmeric and boswellia to find it reduced pain and disability compared with the placebo group (Kulkarni et al., 1991). Taken together, these scientific studies and traditional knowledge of ashwagandha imply that it is a powerful medicine with the potential to rejuvenate and restore various systems of the body.

Gotu Kola

Asiatic_Pennywort_wikicommons

Gotu kola is a creeping medicinal herb native to tropical areas of India, Sri Lanka, and other parts of southeast Asia (Kuhn and Winston, 2000). Folk lore in Sri Lanka tells it increases longevity and lifespan, first observed from elephants who used to eat the gotu kola plant. Like ashwagandha, it has been found to have anti-oxidant properties and has support using experimental models for its use as a neuroprotective agent (Kumar and Gupta, 2003). Similar to other Indian and Chinese tonic herbs, it has been found to be able to suppress (Punturee  et al., 2005) or stimulate (Jayathirtha et al., 2004) the immune system in models, depending on the context, therefore it has immunomodulatory activity. Like ashwagandha, it has neuroregenerative properties and is capable of stimulating nerve regrowth in models of nerve damage (Soumyanath et al., 2005). There is one human double blind placebo controlled study which demonstrated significant effect versus a placebo in the reduction of anxiety (Bradwejn et al., 2000). I expect further studies of this important rasayana herb will support its traditional application for a wide variety of diseases which include psoriasis, rheumatoid arthritis, cognitive decline, and several others.

Bacopa

bacopa_wikicommons

Bacopa is a creeping medicinal plant that is found in damp, marshy areas throughout India (Russo et al., 2005). It grows white flowers and branches with bright green fleshly leaves. It is known as ‘Brahmi’, this word is derived from ‘Brahma’, who is known as the mythical creator God in one school of Hinduism. Bacopa has traditional use in Ayruveda as a medhya rasayana, a rejuvenative for improving the brain and nerves. It has been observed in vivo models to have anti-oxidant and anti-inflammatory activities (Bhattacharya et al., 2000; Channa et al., 2006). More precisely, anti-oxidant activity has been detected in the brain of models (Bhattacharya et al., 2000). This the authors hypothesised is responsible for cognition enhancing effects often seen in human trials (Roodenrys et al., 2002). These studies point to bacopa being useful in treating degenerative cognitive disorders such as Alzheimer’s. In the future, I expect more studies will confirm the medicinal potency of bacopa.

Turmeric

Curcuma_longa_of_Chinna_Salem

Turmeric is a perennial herb that has a short stem and big leaves which produce its characteristic oblong shaped, branched, brown coloured roots (Chattopadhyay et al., 2004). It is the root which contains curcumin which gives it a yellow colour and from which turmeric extract, which has medicinal properties, is extracted from. Turmeric is a tropical growing plant native to Southern Asia and notably is closely related to ginger, another medicinal herb. Turmeric has been shown using experimental models and human studies to possess anti-oxidant (Selvam et al., 2005), anti-inflammatory (Panahi et al., 2014), and anti-tumour (Kuttan et al., 1985) properties. Over 6 weeks it has been shown to decrease the pain of osteoarthritis in a double-blind placebo controlled trial (Panahi et al., 2014). Remarkably, in another well conducted study, it was shown to be effective at reducing depression (Lopresti et al., 2014). These human and experimental model studies support the traditional role of turmeric as a highly versatile rasayana herb capable of acting to improve seemingly unrelated diseases.

Conclusions

There is now an increasing body of scientific evidence to support the notion of the ‘rasayana’ herb, a powerful group of rejuvenative tonic herbs used in the ancient system of Ayurvedic medicine. I think this classification of herbs could be extended to include the ‘superior tonics’ of traditional Chinese medicine and several Western herbs. Rasayana (restorative) tonic herbs are a broad classification, but they must be; 1) non-toxic and non-habit forming even long term, 2) support and restore the function of organs or systems with time, 3) provide protection against disease and ageing. These characteristics are those of the ideal medicine.

References:

Bhattacharya, A., S. Ghosal, and S. K. Bhattacharya. “Anti-oxidant effect of Withania somnifera glycowithanolides in chronic footshock stress-induced perturbations of oxidative free radical scavenging enzymes and lipid peroxidation in rat frontal cortex and striatum.” Journal of Ethnopharmacology 74.1 (2001): 1-6.

Bhattacharya, S. K., et al. “Antioxidant activity of Bacopa monniera in rat frontal cortex, striatum and hippocampus.” Phytotherapy Research 14.3 (2000): 174-179.

Bradwejn, Jacques, et al. “A double-blind, placebo-controlled study on the effects of Gotu Kola (Centella asiatica) on acoustic startle response in healthy subjects.” Journal of clinical psychopharmacology 20.6 (2000): 680-684.

Chandra, Sangita, et al. “Evaluation of anti-inflammatory effect of ashwagandha: a preliminary study in vitro.” Pharmacognosy Journal 4.29 (2012): 47-49.

Chandrasekhar, K., Jyoti Kapoor, and Sridhar Anishetty. “A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full-spectrum extract of ashwagandha root in reducing stress and anxiety in adults.” Indian Journal of Psychological Medicine 34.3 (2012): 255.

Channa, Shabana, et al. “Anti-inflammatory activity of Bacopa monniera in rodents.” Journal of ethnopharmacology 104.1 (2006): 286-289.

Chattopadhyay, Ishita, et al. “Turmeric and curcumin: Biological actions and medicinal applications.” CURRENT SCIENCE-BANGALORE- 87 (2004): 44-53.

Gardner, Tanya, and A. H. P. Level. “The Characteristics, Benefits and Application of Ashwagandha in the West.” Image 2 (2015): 2.

Jayathirtha, M. G., and S. H. Mishra. “Preliminary immunomodulatory activities of methanol extracts of Eclipta alba and Centella asiatica.” Phytomedicine 11.4 (2004): 361-365.

Kuhn, Merrily A., and David Winston. Herbal therapy and supplements: a scientific and traditional approach. Lippincott Williams & Wilkins, 2000.

Kulkarni, R. R., et al. “Treatment of osteoarthritis with a herbomineral formulation: a double-blind, placebo-controlled, cross-over study.” Journal of ethnopharmacology 33.1-2 (1991): 91-95.

Kurapati, Kesava Rao Venkata, et al. “Ashwagandha (Withania somnifera) reverses β-amyloid 1-42 induced toxicity in human neuronal cells: implications in HIV-associated neurocognitive disorders (HAND).” PLoS One 8.10 (2013): e77624.

Kuttan, Ramadasan, et al. “Potential anticancer activity of turmeric (Curcuma longa).” Cancer letters 29.2 (1985): 197-202.

Lopresti, Adrian L., et al. “Curcumin for the treatment of major depression: a randomised, double-blind, placebo controlled study.” Journal of affective disorders 167 (2014): 368-375.

Nakayama, Natsuki, and Chihiro Tohda. “Withanoside IV improves hindlimb function by facilitating axonal growth and increase in peripheral nervous system myelin level after spinal cord injury.” Neuroscience research 58.2 (2007): 176-182.

Panahi, Yunes, et al. “Curcuminoid Treatment for Knee Osteoarthritis: A Randomized Double‐Blind Placebo‐Controlled Trial.” Phytotherapy Research 28.11 (2014): 1625-1631.

Punturee, Khanittha, et al. “Immunomodulatory activities of Centella asiatica and Rhinacanthus nasutus extracts.” Asian Pacific Journal of Cancer Prevention 6.3 (2005): 396.

Puri, Harbans Singh. Rasayana: ayurvedic herbs for longevity and rejuvenation. CRC Press, 2003.

Rege, Nirmala N., Urmila M. Thatte, and Sharadini A. Dahanukar. “Adaptogenic properties of six rasayana herbs used in Ayurvedic medicine.” Phytotherapy Research 13.4 (1999): 275-291.

Roodenrys, Steven, et al. “Chronic effects of Brahmi (Bacopa monnieri) on human memory.” Neuropsychopharmacology 27.2 (2002): 279-281.

Russo, A., and F. Borrelli. “Bacopa monniera, a reputed nootropic plant: an overview.” Phytomedicine 12.4 (2005): 305-317.

Selvam, R., et al. “The anti-oxidant activity of turmeric (Curcuma longa).” Journal of Ethnopharmacology 47.2 (1995): 59-67.

Soumyanath, Amala, et al. “Centella asiatica accelerates nerve regeneration upon oral administration and contains multiple active fractions increasing neurite elongation in‐vitro.” Journal of Pharmacy and Pharmacology 57.9 (2005): 1221-1229.

Veerendra Kumar, M. H., and Y. K. Gupta. “Effect of Centella asiatica on cognition and oxidative stress in an intracerebroventricular streptozotocin model of Alzheimer’s disease in rats.” Clinical and Experimental Pharmacology and Physiology 30.5‐6 (2003): 336-342.

Widodo, Nashi, et al. “Selective killing of cancer cells by leaf extract of Ashwagandha: identification of a tumor-inhibitory factor and the first molecular insights to its effect.” Clinical Cancer Research 13.7 (2007): 2298-2306.

Winston, David, and Steven Maimes. Adaptogens: herbs for strength, stamina, and stress relief. Inner Traditions/Bear & Co, 2007.

How do you increase lifespan using herbs and lifestyle?

To begin to answer this first we must examine what aging is. Aging is a really complex process, however, there is now a significant body of evidence suggesting the creation of reactive oxygen species and the ability to respond to this oxidative stress as key factors determining longevity (Toren and Holbrook, 2000). This has led some to suggest consuming more anti-oxidant containing foods will increase life span (Packer et al., 1995). In addition, from various studies it has become clear that chronic inflammation has a serious role in a wide range of age related diseases, including; diabetes, cardiovascular, and autoimmune diseases (Khansari et al., 2009). Inflammatory processes are also known to cause oxidative stress and reduce anti-oxidant capacity. Over produced free radicals tend to damage DNA and be a predisposing factor in cancer development. Heart disease, depression, aging, and cancer are characterized by an increased level of interleukin-1, a proinflammatory cytokine (Simopoulos et al., 2002). In summary, inflammation and oxidative stress are strongly linked to developing disease, disease severity, and reducing lifespan.

Vegetables and fruits are known to be rich in anti-oxidant activity and are strongly implicated in reducing the risk of cancer (Gundgaard et al., 2003). The anti-oxidant and anti-tumour activities of vegetables and fruits are thought to be related to additive and synergistic effects of many phytochemicals in them (Liu et al., 2003). These phytochemicals such as flavonoids and anti-oxidants have been associated with reduced risk of heart disease, stroke, and markers of inflammation (Holt et al., 2009). This leads one to ask, are there other natural products that can increase lifespan? We already know omega3 is effective against reducing the severity of many conditions such as autoimmune diseases, through its anti-inflammatory activity (Simopoulos et al., 2002). Increased intake of fish is linked to living longer and is especially evident in Japan (Mizushima et al., 1997). However, in the diversity of the natural world, it is likely other such naturally occurring compounds exist which can naturally fight inflammation, oxidative stress, and so disease and therefore increase lifespan.

This is when it is appropriate to introduce the concept of tonic herbs in Indian and Chinese medicine. In Indian herbal medicine, or Ayruveda, which dates back 7000 years, one of its 8 branches is called Rasayana Tantra (Puri et al., 2003). Rasayana medicine is rejuvenating medicine. In Ayruveda it is considered it the path to restore youth, alleviate disease, and bestow longevity (increase lifespan). Rasayana plants are said to have the following properties; anti-aging, life strengthening, brain and mind strengthening, and disease preventing. A similar approach can be observed in traditional Chinese medicine with the superior tonic herbs (Teeguarden et al., 1998). These superior herbs are understood to work towards health and strengthening the body, they are also supposedly completely non-toxic even at higher doses. They are thought of as being similar to foods and to work in the long term to give cumulative wide ranging beneficial effects to the body. Both Ayruvedic and Chinese tonics have become known as adaptogens in the West, a term that means they can resist stress and normalise various functions (Winston, 2007). This terminology was coined by Soviet scientist, Nikolai Lazarev, and was based on extensive research conducted in the USSR from the 1940s through to the 1960s. This work began as the USSR sought tonics to strengthen and improve the function of the Soviet people. I will now turn to cover two important tonic herbs closely linked to increasing lifespan.

An example of a Chinese tonic herb indicated for longevity is reishi (Castleman, 2001). It is known as the mushroom of immortality and was thought by Chinese doctors to increase the duration of lifespan (Babu, 2008). Reishi is known for anti-oxidant, anti-inflammatory, and anti-tumour effects (Jones et al., 2000; Akihisa et al., 2007). However, it is more complex than being an anti-inflammatory agent as it has been found to stimulate the immune system in humans (Jin et al., 2012), which is hypothesised to be the reason why it is popular in Japan and China for cancer treatment. This phenomenon of both stimulating the immune system and repressing excess inflammation is a typical property of the adaptogens and a reason why they are such powerful balancing tonic herbs. One study recently found that a reishi containing extract increased the lifespans of mice (Wu et al., 2011), this supports the traditional view in China of reishi, that it promotes longevity and overall health.

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Another explanation for why reishi may be a longevity promoting agent is it’s effect on the heart and blood pressure. Reishi has been found to lower blood pressure in hypertensive rats (Kabir et al., 1988). Furthermore, beta blockers, which lower blood pressure and stabilize heart arrhythmias have been found to increase the lifespan of mice (Spindler et al., 2013). β1-adrenergic receptors which are blocked by beta blockers tend to become more active as the aging process continues and their activation results in higher blood pressure and heart instabilities. A logical conclusion from this would be reishi may act in a similar, but more sophisticated manner to beta blockers, by lowering blood pressure and stabilizing the heart to confer longevity.

An example of a Ayruvedic tonic herb (a rasayana/ rejuvenator), indicated for longevity is gotu kola. Gotu kola is a weedy creeping herb native to tropical areas of India, Sri Lanka, and southeast Asia (Kuhn and Winston, 2000). It is said long ago, the native Sinhalese of Ceylon (now Sri Lanka) observed that elephants, renowned for their longevity, loved eating the round-lobed leaves of gotu kola (Castleman, 2001). Thus, the herb gained a reputation as a longevity promoter, a Sinhalese proverb said, ‘Two leaves a day keeps old age away’. Gotu kola has anti-oxidant and neuroprotective activities that could be linked to why traditionally it is used to treat cognitive disorders and confers longevity (Kumar and Gupta, 2003). Similar to reishi, it has the dual properties of being able to reduce inflammation, but also stimulates the immune system (Jayathirtha et al., 2004; Punturee et al., 2005). Gotu kola has similar balancing properties to reishi I think result in protecting the body from stress and so being able to increase lifespan.

Gotu Kola (Centella Asiatica) Overview, Health Benefits, Side effects (3)

Of relevance to this article is the mythical character Li Chin Yuen, a Chinese herbalist and martial artist, who is reported to have lived from 1677 to 1933 (http://www.bionity.com/en/encyclopedia/Li_Ching-Yuen.html) some 256 years. The article ‘Tortoise-Pigeon-Dog’, from the May 15, 1933 issue of TIME magazine described his history. He is said to have born in 1677 in Chyi Jiang Hsie, in the Szechuan province of China. He spent most of his life dwelling in the mountains gathering precious herbs and knowledge of longevity methods. In 1748, when he was 71, he moved to Kai Hsien to join the army as teacher of the martial arts. In 1927, Li Ching-Yuen was invited by General Yang Sen to see him in Wann Hsien, Szechuan. The general was fascinated by his young appearance, strength and abilities despite his advanced age. After his death, a year later, General Yang Sen decided to investigate the truth about his background and age. He wrote a report that was published later. In 1933, people interviewed from his home area recalled seeing him when they were just children, and said that he hadn’t aged much during their lifetime. Some others reported that he had been friends with their grandfathers. While it is unclear how much of this is true, Li Chin Yuen was said to have used gotu kola, reishi, fo-ti, and Asian ginseng during his lifetime and to have practiced a lot of qi-gong.

My view is, I suspect that Li Chin Tuen did live a very long time and this partly was due to him keeping down excess oxidative stress and inflammation, while protecting the various systems of the body (e.g. the heart) using diet and tonic herbs. He also seemed to keep a calm and relaxed body and mind with qi-gong, living in a natural environment, and in his own words he, ‘slept like a dog’. So increasing lifespan and protecting yourself from disease requires a holistic approach. Perhaps Li Chin Tuen’s most important lesson is that he lived a long time while cultivating a calm mind.

Note: This article is speculative and any adaptogen use should be accompanied with good lifestyle habits. Certain adaptogens are better suited for certain individuals according to their constitution. They also can cause insomnia in some persons and sometimes are better taken in the morning or dosage needs to be adjusted. We recommend reading this PDF by Paul Bergner, an herbalist highly experienced with using the adaptogens if you are thinking of using them on yourself or on others (link).

References:

Teeguarden, Ron. Radiant Health: The Ancient Wisdom of the Chinese Tonic Herbs. Grand Central Publishing, 1998.

Puri, Harbans Singh. Rasayana: ayurvedic herbs for longevity and rejuvenation. CRC Press, 2003.

Packer, L. “Oxidative stress, antioxidants, aging and disease.” Oxidative stress and aging. Birkhäuser Basel, 1995. 1-14

Finkel, Toren, and Nikki J. Holbrook. “Oxidants, oxidative stress and the biology of ageing.” Nature 408.6809 (2000): 239-247.

Kabir, Yearul, Shuichi Kimura, and Tsutomu Tamura. “Dietary effect of Ganoderma lucidum mushroom on blood pressure and lipid levels in spontaneously hypertensive rats (SHR).” Journal of nutritional science and vitaminology 34.4 (1988): 433-438.

Kaur, Charanjit, and Harish C. Kapoor. “Antioxidants in fruits and vegetables–the millennium’s health.” International journal of food science & technology 36.7 (2001): 703-725.

Gundgaard, Jens, et al. “Increased intake of fruit and vegetables: estimation of impact in terms of life expectancy and healthcare costs.” Public health nutrition 6.01 (2003): 25-30.

Liu, Rui Hai. “Health benefits of fruit and vegetables are from additive and synergistic combinations of phytochemicals.” The American journal of clinical nutrition 78.3 (2003): 517S-520S.

Khansari, Nemat, Yadollah Shakiba, and Mahdi Mahmoudi. “Chronic inflammation and oxidative stress as a major cause of age-related diseases and cancer.” Recent patents on inflammation & allergy drug discovery 3.1 (2009): 73-80.

Simopoulos, Artemis P. “Omega-3 fatty acids in inflammation and autoimmune diseases.” Journal of the American College of Nutrition 21.6 (2002): 495-505.

Veerendra Kumar, M. H., and Y. K. Gupta. “Effect of Centella asiatica on cognition and oxidative stress in an intracerebroventricular streptozotocin model of Alzheimer’s disease in rats.” Clinical and Experimental Pharmacology and Physiology 30.5‐6 (2003): 336-342.

Holt, Erica M., et al. “Fruit and vegetable consumption and its relation to markers of inflammation and oxidative stress in adolescents.” Journal of the American Dietetic Association 109.3 (2009): 414-421.

Mizushima, Shunsaku, et al. “Fish intake and cardiovascular risk among middle-aged Japanese in Japan and Brazil.” Journal of cardiovascular risk 4.3 (1997): 191-199.

Jones, Susan, and Kainoor K. Janardhanan. “Antioxidant and antitumor activity of Ganoderma lucidum (Curt.: Fr.) P. Karst.—Reishi (Aphyllophoromycetideae) from South India.” International Journal of Medicinal Mushrooms 2.3 (2000).

Akihisa, Toshihiro, et al. “Anti‐Inflammatory and Anti‐Tumor‐Promoting Effects of Triterpene Acids and Sterols from the Fungus Ganoderma lucidum.” Chemistry & biodiversity 4.2 (2007): 224-231.

Castleman, Michael. “The new healing herbs.” Bantam Book, New York (2001): 465-471.

Jin, Xingzhong, et al. “Ganoderma lucidum (Reishi mushroom) for cancer treatment.” The Cochrane Library (2012).

Winston, David, and Steven Maimes. Adaptogens: herbs for strength, stamina, and stress relief. Inner Traditions/Bear & Co, 2007.

Wu, Zimei, et al. “ReishiMax extends the lifespan of mice: A preliminary report.” The FASEB Journal 25.1 Supplement (2011): 601-2.

Babu, P.D. and Subhasree, R.S., 2008. The sacred mushroom “Reishi”-a review. The American-Eurasian Journal of Botany, 1(3), pp.107-110.

Kuhn, Merrily A., and David Winston. Herbal therapy and supplements: a scientific and traditional approach. Lippincott Williams & Wilkins, 2000.

Jayathirtha, M. G., and S. H. Mishra. “Preliminary immunomodulatory activities of methanol extracts of Eclipta alba and Centella asiatica.” Phytomedicine 11.4 (2004): 361-365.

Punturee, Khanittha, et al. “Immunomodulatory activities of Centella asiatica and Rhinacanthus nasutus extracts.” Asian Pacific Journal of Cancer Prevention 6.3 (2005): 396.

Spindler, Stephen R., et al. “β1-Adrenergic receptor blockade extends the life span of Drosophila and long-lived mice.” Age 35.6 (2013): 2099-2109.