The alterative herbs

The alterative herbs occupy an important position in traditional Western herbalism, although we have only a little information about how they work, many different and diverse traditional sources can attest to their medicinal efficiency. Overall, they are thought to work by acting as ‘cleansing’ agents, meaning they stimulate the activity of the excretory organs such as the liver and kidneys to remove unwanted materials from the body. Unfortunately, this is one of the least satisfying definitions we have of any herbal action and is regularly subject to scrutiny. However, what is clear is alteratives do work for certain kinds of problems and people, we just don’t know exactly how yet.

Alteratives appear to beneficially alter the course of chronic diseases with a specificity towards certain diseases that involve chronic inflammation or ‘damp heat’; such as psoriasis, acne, and rheumatoid arthritis. There is some preliminary scientific support for these ideas we will discuss later. As the definition is vague, it can be helpful to study some example definitions of an alterative from traditional herbalism text books. Of these examples, I find Maria Groves to provide the most clear and succinct definition.

David Hoffman: ‘Alteratives gradually alter and correct a ‘polluted’ condition of the blood stream and restore a healthier functioning. The way alteratives work is poorly understood, but they certainly work…(they are) perhaps the herbs most often used in the context of skin conditions, the roots of which lie deep within the metabolism of the individual. They cleanse the whole of the body, but their activity is focused in different areas, some in the kidneys, some in the liver… and they have to be chosen according to their specific indications’ (Hoffman, 1988).

Harvey Felter: ‘A drug which causes a favourable change or alteration in the processes of nutrition and repair, probably through some unknown way improving metabolism.’ (Felter, 1922).

John Scudder: ‘We suppose… They may change the condition of the blood by a direct influence exerted upon it… They may in some manner effect the removal of the worn-out tissues, and favour the process of nutrition… They may neutralize or change the character of decomposing or noxious agents that exist in the system as the result of some pathological process, or that have been introduced from without… They undoubtedly favor elimination by stimulating the excretory organs to increased activity.’ (Scudder, 1898)

Maria Groves: ‘Alteratives improve the body’s detoxification processes and efficient removal of metabolic wastes. They often encourage detoxification of the blood and interstitial fluid via the liver, lymphatic system, and the kidneys’ (Groves, 2016)

Alterative actions

Different alteratives have greater or lesser affinities for different excretory organs, but what is in common is they will stimulate activity of a particular organ to increase elimination. To explain further, Maria Groves subdivides alteratives to include those with the following actions (Groves, 2016):

Lymphagogues (lymph stimulants/ movers): Burdock root, red clover, sarsaparilla

Choleretics and cholagogues (liver stimulants/ movers): Dandelion, burdock root, yellow dock root

Diuretics (kidney stimulants/ movers): Dandelion, nettles, sarsaparilla

We will now turn to examine some of the classic alteratives from Western herbalism, considering both traditional knowledge and preliminary scientific data. One of the most well known and researched is sarsaparilla.

Sarsaparilla

sarsawiki

Sarsaparilla is a woody trailing perennial vine that may refer to one of a number of similar species scattered throughout the world (Kuhn and Winston, 2000). Sarsaparilla is cultivated in Mexico, Jamaica, China, and Central and Southern America. ‘Sarsaparilla’ as a name comes from Spanish words, prickly (zarsa), vine (parra), and small (illa). It is said sarsaparilla was used by the ancient Greeks as an antidote to poisons, however, it only became widely popular in Europe medicinally during the 16th century when Spanish explorers discovered the Caribbean species (Castleman, 2001). Native Americans and also Caribbean Indians used sarsaparilla to treat skin and urinary diseases. They saw sarasaparilla as a tonic herb for preserving youth and strength. Mexican sarsaparilla was transported to Spain around 1530 and then used as a treatment for syphilis and also as a ‘strengthening tonic’. It was used by Nicholas Culpeper, a famous 17th century English herbalist, for rheumatism and ‘many kinds of diseases’ (Culpeper, 1814).

In more modern times, David Hoffman in his text Holistic Herbal mentions sarsaparilla is a widely applicable alterative and that it may be used to aid proper functioning of the body as a whole (Hoffman, 1988). It is indicated for scaly skin conditions like psoriasis and also as part of a wider treatment for rheumatism, especially rheumatoid arthritis. For psoriasis, sarsaparilla is often combined with similar alteratives to increase medicinal power such as burdock root and yellow dock. Sarsaparilla roots contain a high relative abundance of steroidal saponins that are related to its medicinal properties (Challinor et al., 2012). Steroidal saponins display a range of bioactivities, including cytotoxic, hemolytic, anti-inflammatory, anti-fungal, and anti-bacterial properties.

Sarasaparilla is a relatively well studied alterative and preliminary studies give us insights into how alteratives may function physiologically. For example, gout is a disease associated with the accumulation of urate in the blood stream. In one study, the authors found an extract of sarsaparilla was effective in enhancing urate excretion via the kidneys of hyperuricemic mice (Wu et al., 2014). This supports the role of alteratives in the stimulation of the excretory organs that results in removal of unwanted compounds from the body. Another similar study investigated metabolic syndrome. Metabolic syndrome is a metabolic disorder associated with an increased risk of developing kidney failure, cardiovascular, and cerebrovascular diseases. In this study, using a mouse model of metabolic syndrome, the authors found sarsaparilla root extract was able to control weight gain and was able to decrease elevated levels of triglycerides (fatty molecules) by 60% (Amaro et al., 2014). This study supports the traditional role of alteratives as beneficial modulators of metabolism. While these studies were conducted in animal models, which are not as reliable, there is one human clinical trial of great interest.

In the 1940s when there was more interest in sarsaparilla, one study observed a greater improvement with sarsaparilla extract treatment in psoriasis patients opposed to those patients who received a placebo (Thurmon et al., 1942). 18% of those patients treated with the sarsaparilla extract experienced total remission, while only 6% on the placebo. This study was published in the New England Journal Of Medicine, a prestigious journal. However, in these early days experimental standards were less demanding and this clinical trial does not seem to have been blinded and statistical analysis was not performed. Regardless of this, I think this study shows great promise for the medicinal potential of sarsaparilla in humans. Perhaps in the future, as herbs become more popular again in Western culture as medicines, further studies will expand on the role of sarsaparilla extracts in treating psoriasis and other chronic inflammatory diseases.

Note: Alteratives are often rather drying to the constitution, so care must be taken not to dry some one out too much by using moistening herbs or avoiding the more drying alteratives. More moistening alteratives include red clover and burdock. They also have been known to be too much for older weak people to handle who may respond better to tonification (i.e. use of the adaptogens). It is best to generally proceed with caution with these herbs.

References

Amaro, Carol Arely Botello, et al. “Hypoglycemic and hypotensive activity of a root extract of Smilax aristolochiifolia, standardized on N-trans-feruloyl-tyramine.” Molecules 19.8 (2014): 11366-11384.

Challinor, Victoria L., et al. “Steroidal saponins from the roots of Smilax sp.: structure and bioactivity.” Steroids 77.5 (2012): 504-511.

Culpeper, Nicholas. Culpeper’s complete herbal. (1814).

Felter, Harvey. The Eclectic Materia Medica, Pharmacology, and Therapeutic (1922)

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

Hoffman, David. Holistic herbal. Element Books. (1988).

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

Scudder, John. The American Eclectic Materia Medica and Therapeutics (1898)

Thurmon, Francis M. “The treatment of psoriasis with a sarsaparilla compound.” New England Journal of Medicine 227.4 (1942): 128-133.

Wu, Xiao-Hui, et al. “Smilax riparia reduces hyperuricemia in mice as a potential treatment of gout.” The American journal of Chinese medicine 42.01 (2014): 257-259.

Do medicinal mushrooms work against cancer?

Edible mushrooms, such as reishi, maitake, and cordyceps, have long been used in Japan and China as food, but also medicines (Mizuno et al., 1995). These medicinal mushrooms have a deep history of medicinal use that extends back thousands of years in traditional Chinese medicine, and have long been associated with longevity (Castleman, 2001). In cancer research, there is special interest in the polysaccharides of these mushrooms present in the fruiting bodies and mycelium as they are responsible for anti-tumour and immunostimulating properties (Wasser, 2010). I will now critically discuss the current state of cancer science related to these polysaccharides and medicinal mushrooms.

PSK

A mushroom polysaccharide called polysaccharide-K (PSK) was originally extracted by Japanese researchers and used in various clinical trials in Asia together with conventional therapies (Fisher et al., 2002). The result of these trials were its acceptance as a mainstream anti-cancer drug in Japan to complement the existing chemotherapy and surgical techniques. PSK is a polysaccharide from the fungus Coriolus versicolor. PSK has shown efficiency in helping maintain remission in colorectal cancer patients after surgery (Torisu et al., 1990), a meta-analysis of different clinical trials in 2006 supported this discovery (Sakamoto et al., 2006). Another high quality study published in the Lancet found PSK supported ordinary chemotherapy treatment for gastric cancer after surgery and significantly increased five year survival and disease free survival rates (Nakazato et al., 1994). PSK increases the ability of the host to defend itself against the cancer (Fisher et al., 2002). It may do this by increasing white blood cell activation and response via increasing levels of specific cytokines. However, it is not just PSK which displays anti-tumour potential, there are several mushroom extracts which show promise.

Reishi

A mushroom of particular value in traditional Chinese medicine is reishi, this mushroom has been known as ‘the mushroom of immortality’ since ancient times (Castleman, 2001). Reishi has an array of health benefits and has anti-oxidant, anti-tumour, anti-inflammatory properties (Joseph et al., 2011; Baskar et al., 2008). An interesting study appeared in the American journal PNAS in 2013 on the mechanism by which reishi has anti-tumour effects (Liao et al., 2013). In this paper, they demonstrated that mice injected with reishi polysaccharides produced antibodies against lung cancer cells. This resulted in increased cytotoxicity against the cancer cells and reduction of inflammatory mediators associated with the tumour. However, although promising, this study was using an animal model and high quality human clinical trials are required to further assess the anti-cancer potential of reishi.

Ganoderma_lucidum_01_wiki

Human Studies

There are a number of human studies with some preliminary data which is interesting. A randomised placebo controlled study of reishi polysaccharides in patients with lung cancer found increase in leukocyte and natural killer cell activity (Gao et al., 2003). They also observed better quality of life in the reishi mushroom patients and stability of disease. Improvements were seen in the reishi group in reduction of cancer related fever, cough, weakness, sweating and insomnia. The dose for this study was 600mg of patented extract a day, which seems a little low, as herbalists suggest between 3-6 grams of polysaccharide extracts for serious diseases like cancer (Powell, 2015). This translates to somewhere in the region of 10g of mycelium or fruiting body extract of reishi per day. However, this study only suggests that reishi may be effective as a complementary treatment for cancer patients, much further work is required (Gao et al., 2003).

Currently, we can be sure at least that reishi stimulates the immune system as this was seen in another well controlled human study also (Wicks et al., 2007). Another study documented a patient with breast cancer who used reishi extract as a complementary therapy (Chen et al., 2007). According to this account, reishi helped reduce side effects from chemotherapy and radiotherapy, improved quality of life, and assisted tumour shrinkage.

Like reishi, there is similar interest in the turkey tail mushroom (trametes versicolor) and a phase I clinical trial indicated immune up-regulation in breast cancer patients taking extract of this mushroom (Torkelson et al., 2012). This mushroom made headlines in 2012 as researchers were given $5.4 million for continuing their investigation of its ability to assist conventional cancer therapy. This is a very large amount of money for a complementary medicine study. These pioneering researchers of the turkey tail mushroom are aiming to create effective natural anti-tumour therapies without the harsh side effects of pharmaceutical drugs. Similar to reishi, the turkey tail mushroom has been shown to be effective against tumours in mice (Harhaji et al., 2008).

Grifola_frondosa_57503_wiki

(Above) The maitake mushroom, another fungus where there is interest in it’s anti-tumour properties.

Conclusions

So it is not a good idea to throw away conventional medicine and run into the forest to hunt mushrooms. However, as research funding into complementary therapy grows, it is just a matter of time before convincing evidence regarding the human anti-tumor medicinal activity of mushrooms becomes available. In vivo and ex vivo experiments in experimental models imply mushrooms such as reishi, turkey tail, and cordyceps, will have a role in reducing side effects from chemotherapy, improving the efficiency of standard therapy, and possibly, even as a standalone therapy. The demonstrated efficiency of PSK in several high quality clinical trials supports the potential of medicinal mushrooms in the fight against cancer. What is needed now is more human clinical studies.

References

Baskar, R., et al. “Free radical scavenging activity of antitumour polysaccharide fractions isolated from Ganoderma lucidum (Fr.) P. karst.” (2008).

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

Chen, Alice W., and John Seleen. “Potential benefits of Ling Zhi or Reishi mushroom Ganoderma lucidum (W. Curt.: Fr.) P. Karst.(Aphyllophoromycetideae) to breast cancer patients.” International Journal of Medicinal Mushrooms 9.1 (2007).

Fisher, Monte, and Li-Xi Yang. “Anticancer effects and mechanisms of polysaccharide-K (PSK): implications of cancer immunotherapy.” Anticancer research 22.3 (2002): 1737-1754.

Gao, Yihuai, et al. “A randomized, placebo-controlled, multicenter study of Ganoderma lucidum (W. Curt.: Fr.) Lloyd (Aphyllophoromycetideae) polysaccharides (Ganopoly®) in patients with advanced lung cancer.” International Journal of Medicinal Mushrooms 5.4 (2003).

Harhaji, L. J., et al. “Anti-tumor effect of Coriolus versicolor methanol extract against mouse B16 melanoma cells: in vitro and in vivo study.” Food and chemical toxicology 46.5 (2008): 1825-1833.

Joseph, Soniamol, et al. “Antitumor and anti-inflammatory activities of polysaccharides isolated from Ganoderma lucidum.” Acta pharmaceutica 61.3 (2011): 335-342.

Liao, Shih-Fen, et al. “Immunization of fucose-containing polysaccharides from Reishi mushroom induces antibodies to tumor-associated Globo H-series epitopes.” Proceedings of the National Academy of Sciences 110.34 (2013): 13809-13814.

Mizuno, Takashi, Tadamoto Sakai, and Goro Chihara. “Health foods and medicinal usages of mushrooms.” Food Reviews International 11.1 (1995): 69-81.

Nakazato, Hiroaki, et al. “Efficacy of immunochemotherapy as adjuvant treatment after curative resection of gastric cancer.” The Lancet 343.8906 (1994): 1122-1126.

Powell, Martin. Medicinal Mushrooms-A Clinical Guide. Mycology Press, 2015.

Sakamoto, Junichi, et al. “Efficacy of adjuvant immunochemotherapy with polysaccharide K for patients with curatively resected colorectal cancer: a meta-analysis of centrally randomized controlled clinical trials.” Cancer Immunology, Immunotherapy 55.4 (2006): 404-411.

Torisu, Motomichi, et al. “Significant prolongation of disease-free period gained by oral polysaccharide K (PSK) administration after curative surgical operation of colorectal cancer.” Cancer Immunology, Immunotherapy 31.5 (1990): 261-268.

Torkelson, Carolyn J., et al. “Phase 1 clinical trial of Trametes versicolor in women with breast cancer.” ISRN oncology 2012 (2012).

Wasser, Solomon P. “Medicinal mushroom science: history, current status, future trends, and unsolved problems.” International Journal of Medicinal Mushrooms 12.1 (2010).

Wicks, Sheila M., et al. “Safety and tolerability of Ganoderma lucidum in healthy subjects: a double-blind randomized placebo-controlled trial.” The American journal of Chinese medicine 35.03 (2007): 407-414.

Powerful tonic herbs for the immune system

The rasayana or vital energy (Qi) tonic herbs from Ayurveda or traditional Chinese medicine (TCM) respectively are powerful, often slow acting medicines that act to improve, support, or balance various systems of the body (Winston, 2007). A general scientific term given to these herbs is ‘adaptogens’, a term coined by a Soviet scientist in the 1950s called Dr Nikolai Vasilievich Lazarev (1895–1974), adaptogen is a vague scientific term that means able to resist non-specific stress (Davydov and Krikorian, 2000). Adaptogenic tonic herbs are given special importance in both Ayurvedic and TCM and are considered deeply nourishing for the whole body. In TCM, they are thought to boost the bodies Qi or vital energy.

The adaptogen herbs appear to have a strong affinity for the human immune system. Since they often appear to have both immune stimulating and anti-inflammatory properties, depending on context, they are defined as, ‘immunomodulators’, ‘immune amphoteric’, or ‘immune tonic herbs’ by herbalists. The immune tonics are thought to have a balancing effect on the immune system and therefore have potential for tackling chronic infections, cancer, and autoimmune diseases. Although, certainly I am not advocating using them ahead of mainstream drugs in serious life threatening diseases in this article.

It is important not to confuse herbs that have joint anti-inflammatory and immune stimulating properties (e.g. reishi and astragalus) with herbs that just stimulate the immune system (e.g. echinacea). People with autoimmune diseases may have an aggravation of their disease if their immune system is stimulated, as observed in the case of echinacea (Lee et al., 2004). We shall now turn to examine some of the key immune tonics from our materia medica in more detail.

Reishi

Ganoderma_lucidum_01_wiki

Reishi is also a medicinal mushroom and a superior tonic in TCM. It is known as the mushroom of immortality and the ancient Chinese viewed it as an herb for increasing life-span (Babu, 2008). It has been traditionally used by herbalists across a diverse range of diseases including joint pains and allergic asthma (Winston, 2007). It is the triterpene acids from the fruiting body of reishi that have been found to have anti-inflammatory properties (Akihisa et al., 2007). While it is the polysaccharides from reishi that are responsible for its immune stimulating activity (Chen et al., 2004). It is suitable for boosting the immune systems defenses to prevent colds and other infectious illnesses alongside astragalus, for example.

Reishi has been found to stimulate host immunity in humans with advanced stage cancer (Gao et al., 2003), suggesting its traditional use to treat and complement cancer therapy is justified. A large double blinded human study found reishi was effective against chronic hepatitis B (Gao et al., 2002). A human study found reduction of inflammation in cells and tissues extracted patients with Crohn’s disease with reishi treatment (Liu et al., 2016), although in this case unfortunately a control group was absent, so merely suggests a potential of the herb for autoimmune disease treatment.

Although there is much scientific work that needs to be done to validate the traditional use of reishi, herbalists report reishi effective in treating a range of immunological disorders from various autoimmune conditions to cancer (Powell, 2015). It also is a jointly calming and stimulating herb and therefore may have a role in reducing anxiety, but also increases an individual’s vital energy or Qi with time, with a role in the treatment of chronic fatigue (Groves, 2016).

Ashwagandha

Withania_somnifera_04_wiki

Ashwagandha is considered a rasayana herb in Ayurvedic medicine which translates to rejuvenator. These herbs are said to guide the body towards health. Ashwagandha has been traditionally applied across a range of diseases including, arthritis, fibromyalgia, and polymyositis (Winston, 2007). Ashwagandha root extracts have been found to have anti-inflammatory properties and act as an inhibitor of the complement system (Rasool et al., 2006). It has been shown to have anti-inflammatory properties in animal models of arthritis (Gupta et al., 2014). Ashwagandha, turmeric, and boswellia have been found in formula to reduce the pain of osteoarthritis in humans in a double-blind placebo controlled study (Kulkarni et al., 1991). A later additional well controlled human study supported ashwagandha alone as effective against osteoarthritis (Ramakanth et al., 2016). It is important to mention ashwagandha is one of the less potent immune stimulating adaptogens compared with astragalus or reishi (and other medicinal mushrooms), for example.

Clinical herbalists find ashwagandha particularly useful for treating chronic inflammation (Groves, 2016). Similar to reishi, it has a combined relaxing and stimulating effect and therefore has potential for treating some sleep disorders, anxiety, and fatigue. Ashwagandha and reishi are two of the most widely appropriate herbs in our materia medica and may be considered as supportive tonics in many formula.

Holy Basil

Tulsi_Flower_wiki.jpg

Holy basil or tulsi is another rasayana herb in Ayurvedic medicine with a special affinity for the immune system. It is commonly used in Ayurveda to treat asthma and wide range of other conditions (Jeba et al., 2011). Holy basil has been found to have anti-inflammatory activity in an animal model and more specifically it inhibits arachidonate metabolism (Singh et al., 1996). It also has been found to have immunostimulating properties in experimental models with upregulation of antibody production (Jeba et al., 2011). These immune stimulating activities have also been clearly seen in humans (Mondal et al., 2011). In the human study of healthy individuals, significant increases in IFN, IL-4, T-helper cells, and NK-cells were observed after 4 weeks in comparison with the placebo arm. In support of these findings, herbalists find holy basil useful in treating chronic infections and chronic inflammation (Groves, 2016). Tulsi is one of the most calming of the adaptogenic tonic herbs and may improve sleep and anxiety. It may have a role in treating colds and other infections.

Astragalus

astragalus-115038_1920.jpg

Astragalus is found growing beside forests in Korea, China, and Japan (Kuhn and Winston, 2000). The alternative Chinese name, ‘huang qi’, means, ‘yellow vital force’. In reference to it’s stimulation of the ‘vital force’. Astragalus medicinal roots have been used in China for well over 2000 years and they were described within Shen Nong’s Materia Medica which was written in the Han dynasty (200-250AD), but contains teachings passed on in an oral tradition for many hundreds of years before this time (Shao et al., 2004).

Similar to reishi, astragalus has well known potent immune enhancing properties connected to its polysaccharides (Shao et al., 2004). The immune potentiating properties of astragalus were also detected in vivo as it increased the rejection of a foreign graft in an animal model, the authors concluded that astragalus may have applications in immune depleted patients (Chu et al., 1988). There is good scientific support in humans for astragalus’s role in reducing fatigue, as there was one positive well controlled trial conducted on cancer patients (Chen et al., 2012).

Astragalus is widely used as a tonic by herbalists to support the natural functioning of the immune system (Cho et al., 2007). It may be of application in individuals suffering with chronic infections and to prevent infections occurring. It may have a role in reducing allergies. It is less commonly used to treat autoimmune disorders in contrast to ashwagandha for example, but is especially known for building a strong immune response. It also may be combined with reishi in the treatment of chronic fatigue as both gently stimulate an individuals vital energy with time. It may be combined with echinacea in a pair to fight infections and boost immunity.

Formulation notes

The below formula shows a simple combination of immune tonics that which were discussed in this article. By combining herbs with similar actions it is possible to increase the activity of the formula. This tonic formula may have applications in supporting the immune system to prevent infections, it may also have applications in combating chronic fatigue through stimulating the vital energy. This is a mildly warming formula so is less suitable for pitta types and better for vata.

Immune and vital energy tonic compound

Astragalus (1 part) (warming, moistening)
Reishi (1 part) (warming, neutral)

Contraindications: People undergoing immunosuppressive therapy. Do not take while pregnant due to lack of data.

Summary

The immune tonic herbs are important allies against chronic infections and autoimmune diseases and have been employed by herbalists for many centuries. I should add it is important that these herbs are used in the correct context that includes a healthy diet, e.g. a plant based Paleolithic/ keto style diet and also good lifestyle decisions. This way many immune related diseases may be improved. The immune tonic herbs overlap strongly with the adaptogens, the adaptogens likely have a balancing effect on many systems of the body in a currently poorly scientifically defined way.

Note: If you are not fully comfortable with a DIY approach for your condition for any reason, please do not hesitate to contact a local professional herbalist for more tailored assistance. Inform your doctor before taking any herbs or supplements you are planning to take, especially if you already have a serious illness.

Further reading

http://www.healthylehighvalley.com/LHV/November-2012/Herbs-and-the-Immune-System/

References

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.

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.

Chen, Hung-Sen, et al. “Studies on the immuno-modulating and anti-tumor activities of Ganoderma lucidum (Reishi) polysaccharides.” Bioorganic & medicinal chemistry 12.21 (2004): 5595-5601.

Chen, Hong-Wen, et al. “A novel infusible botanically-derived drug, PG2, for cancer-related fatigue: a phase II double-blind, randomized placebo-controlled study.” Clinical & Investigative Medicine 35.1 (2012): 1-11.

Cho, William CS, and Kwok N. Leung. “In vitro and in vivo anti-tumor effects of Astragalus membranaceus.” Cancer Letters 252.1 (2007): 43-54.

Chu, Da-Tong, W. L. Wong, and G. M. Mavligit. “Immunotherapy with Chinese medicinal herbs. II. Reversal of cyclophosphamide-induced immune suppression by administration of fractionated Astragalus membranaceus in vivo.” Journal of clinical & laboratory immunology 25.3 (1988): 125-129.

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.

Gao, Yihuai, et al. “A Phase I/II Study of a Ganoderma lucidum (Curt.: Fr.) P. Karst.(Ling Zhi, Reishi Mushroom) extract in patients with chronic hepatitis В.” International Journal of Medicinal Mushrooms 4.4 (2002).

Gao, Yihuai, et al. “Effects of Ganopoly®(A ganoderma lucidum polysaccharide extract) on the immune functions in Advanced‐Stage cancer patients.” Immunological investigations 32.3 (2003): 201-215.

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

Gupta, Apurva, and Surendra Singh. “Evaluation of anti-inflammatory effect of Withania somnifera root on collagen-induced arthritis in rats.” Pharmaceutical biology 52.3 (2014): 308-320.

Jeba, C. R., Rama Vaidyanathan, and G. Rameshkumar. “Immunomodulatory activity of aqueous extract of Ocimum sanctum in rat.” International Journal on Pharmaceutical and Biomedical Research 2.1 (2011): 33-38.

Khan, Sheema, et al. “Molecular insight into the immune up-regulatory properties of the leaf extract of Ashwagandha and identification of Th1 immunostimulatory chemical entity.” Vaccine 27.43 (2009): 6080-6087.

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.

Lee, Alice N., and Victoria P. Werth. “Activation of autoimmunity following use of immunostimulatory herbal supplements.” Archives of dermatology 140.6 (2004): 723-727.

Liu, Changda, et al. “Anti-inflammatory Effects of Ganoderma Lucidum Triterpenoid in Human Crohn’s Disease Associated with Down-Regulation of NF-κB Signaling.” Inflammatory bowel diseases 21.8 (2015): 1918.

Mondal, Shankar, et al. “Double-blinded randomized controlled trial for immunomodulatory effects of Tulsi (Ocimum sanctum Linn.) leaf extract on healthy volunteers.” Journal of ethnopharmacology 136.3 (2011): 452-456.

Powell, Martin. Medicinal Mushrooms-A Clinical Guide. Mycology Press, 2015.

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.

Rasool, M., and P. Varalakshmi. “Immunomodulatory role of Withania somnifera root powder on experimental induced inflammation: An in vivo and in vitro study.” Vascular pharmacology 44.6 (2006): 406-410.

Shao, Bao-Mei, et al. “A study on the immune receptors for polysaccharides from the roots of Astragalus membranaceus, a Chinese medicinal herb.” Biochemical and biophysical research communications 320.4 (2004): 1103-1111.

Singh, Surender, D. K. Majumdar, and H. M. S. Rehan. “Evaluation of anti-inflammatory potential of fixed oil of Ocimum sanctum (Holybasil) and its possible mechanism of action.” Journal of Ethnopharmacology 54.1 (1996): 19-26.

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