Today, turmeric is reaching new levels of awareness and respect. As is so often the case, extensive preclinical and clinical research on turmeric over the past few decades has confirmed most of its traditional uses.
Medicine is as old as human life itself because the survival of any species requires that all living things must develop the means to combat disease and optimise health. In the early times of human evolution, people lived in the heart of nature, using all their senses to test and observe the effects of different plants on their health and wellbeing. They evolved their knowledge through trial and error, accidentally as well as inspirationally. Through time these insights became structured into organised systems where a deep understanding of nature led to our ancestors evolving a language and understanding of health and disease. As this detailed knowledge of how to use certain plants for specific ailments became passed from generation to generation the origins of human medicine were born and Ayurveda is one of the earliest and longest surviving organised systems.
Ayurveda, the system of medicine originating in India, has survived as a distinct entity from remote antiquity until the present day. Ayurveda is literally translated as ‘science of life’, it can also be interpreted as ‘the way of living with awareness and promoting longevity’ described in its oldest known texts Charaka Saṃhitā and Suśrutha Saṃhitā (100 BCE and 200 CE). It is called Ayurveda because it tells us which substances, qualities and actions are life enhancing, and which are not (Pole S., 2006).
It is based on three fundamental principles: vāta, pitta and kapha dosha (please see explanation of the dosha below) which comprise the five elements: earth, water, fire, air and ether; these are the components of everything we are and are surrounded by. Vāta is responsible for controlling movements within the body. For example, because of the principle of ‘like increasing like’, if there is dry-cold-windy weather it will increase the dry-cold-‘windy’ qualities in an individual with high vāta. This additional wind can lead to dryness of the skin, constipation and insomnia as the main qualities of vāta are dry, cold and light. Fortunately, and largely thanks to the insights of our ancestors, there are many methods to counteract these imbalances: a simple cup of licorice and/or cinnamon tea, a warm bath or a massage with warm oil (preferably almond oil or any oil with vāta reducing herbs like Maharanayam oil). It is as simple as that…
|Vāta dosha: ‘The vāta dosha is comprised of ākāśa (ether) and vāyu (wind). Vāta is the air element that is held within the confines of ether. It shares qualities familiar to both elements. So, vāta is cold, light, rough, mobile, subtle, clear, dry and astringent. When vāta manifests, these qualities are apparent. The primary site of Vāta is the colon. It also resides in the bladder, thighs, ears, bones and the sense of touch. The root ‘va’ means ‘to spread’ and it is responsible for all movements in the body; the flow of breath and blood, elimination of wastes, expression of speech, it moves the diaphragm, muscles and limbs, regulates the nervous system and it also stimulates the function of the intellect. It is like a current of electricity and is responsible for regulating all electrical impulses in the body-mind. It is the messenger. In fact without vāta the other dosha (pitta and kapha) are inert’ (Pole S., 2006, page 24).|
|Pitta dosha: ‘The Pitta dosha is made up of tejas (fire) and jala (water). The seemingly contradictory combination of fire and water to form pitta is actually complementary. Pitta exists as water or oil in the body, thus pre-serving the tissues from the destructive aspect of fire. It is pungent, hot, penetrating, greasy, oily, sharp, liquid, spreading and sour. Its primary function is transformation. It is the force of metabolic activity in the body associated with the endocrine function, hormone levels, digestion, body temperature, visual perception, hunger, thirst and skin quality. Mentally it plays a role in understanding and in digesting sensory impressions. Again, the five aspects of pitta determine its location in the body. It resides in the eyes, blood, sweat glands, the small intestine, stomach and lymph. Its primary site is in the small intestine’ (Pole S., 2006, page 26).|
|Kapha dosha: ‘The Kapha dosha is a combination of the pṛthivī (earth) and jala (water) elements. As the water element is contained within the earthen structures of the tissues and skin, the dry earth is moistened by the reviving water element. It is slow, heavy, cool, dense, soft, greasy, unctuous, sticky, cloudy, liquid and sweet. Kapha literally holds the body together. It is cohesive, gives shape and form, aids growth and development, lubricates and protects, helps smelling and tasting. It relates to phlegm in the body. It resides in the chest, throat, head, pancreas, stomach, lymph, fat, nose and tongue. Its primary site is the stomach’ (Pole S., 2006, page 27).|
The fundamental principles on which the Ayurvedic system is based are time-tested but it has also evolved as and when new knowledge has been learnt. Both basic and clinical research dates back to at least Avicenna, a Muslim scientist of the tenth and eleventh centuries (Moosavi J., 2009). However, in the Eastern Han period, a medical scientist of Traditional Chinese Medicine named Zhang Zhongjing (150 CE - 219 CE), wrote a sixteen volume work entitled Discussion of Cold Induced Disorders (Shanghan Lun) including the areas of epidemic, external heat disorders, jaundice, gynecology; this document set down a complete set of treatment principals based on clinical experience. Zhang Zhongjing’s theory and prescriptions are still of great practical value today (Wang J.H.).
A great change however, happened in the late 1800s when chemistry was advancing and the focus of those involved in development of medicines changed from whole herb use to single isolated compounds contained within the plant. The responsibility for herb quality passed from herbalists to medical doctors and the materia medica, was generally replaced by pharmacology and pharmacognosy - specializing in the development of drugs from natural products which was then codified into national pharmacopoeias. Subsequently, pharmacopoeias as a quality standard for drugs within national health care approval systems were based on the needs for modern drugs, not traditional herbal medicines. At the same time, the focus changed to research, specialization and high-cost drug approval processes; a medical system more driven by research findings and profits than practitioner or patient need (Upon R, 2015).
In contrast to that, the medical theories of Ayurvedic and Chinese herbal medicine remain intact, continue to evolve, and continue to be practiced according to their same historical foundational principles (Upon R, 2015). There is now the opportunity for the scientific community to review the emphasis on the quality of the whole plant material itself rather than viewing herbal drugs as cocktails of chemicals to be pulled apart, isolated, and manipulated – a process accompanied with high risks leading to serious and fatal adverse drug reactions (ADRs). A meta-analysis of Lazarou et al. on the incidence of (ADR) in hospital patients in the US, demonstrated overall 2,216,000 hospitalized patients had serious ADRs and 106,000 had fatal ADRs in one year, making these reactions between the fourth and sixth leading cause of death (Lazarou et al., 1998).
"Evidence-based Medicine" (see details in box below) is being used to validate the use of modern drugs as well as time-honoured herbal remedies. However, we must be aware to not lose sight of the whole plant while analysing quality marker compounds and other the research findings. Moreover, we should focus on finding new ways to analyse the complex nature of herbal medicine, so that an alternative for health care approval systems can be provided which is meeting the needs of traditional herbal medicines.
Turmeric, one of the most studied traditional herbs, is used here as an example to illustrate its benefits by applying modern research methods.
|In the 1990, the term "Evidence-based Medicine" (EBM) first appeared (Jaeschke and Guyatt, 1999) and was created to integrate individual clinical expertise with the best available external clinical evidence from systematic research (Sackett et al, 1996). It was the consequence of dissatisfaction how research results were incorporated in medical decisions. The first modern step in the development of EBM was the advent in the 1950s of the randomized trial (RT) as a methodology for resolving therapeutic dilemmas (Jaeschke and Guyatt, 1999). Chief among these dilemmas are the recognition of problems associated with the use of more subjective forms of evidence regarding new pharmaceuticals and unknown side-effects (eg. expert opinion unsupported by systematic research, uncontrolled observations). Documented reports of such failures are numerous: some agents with inotropic properties, despite physiologic promise, actually increase mortality (Packer et al. 1991). Similarly, some antiarrhythmic agents have been shown to both eliminate non-cardiac arrhythmias and increase mortality (Echt et al., 1991). And maybe one of the biggest catastrophes: the unknown teratogenic effects of thalidomide in the late 1950s: a failure to demonstrate teratogenic effects experimentally in animal experiments did not prove the drug's harmlessness to the human embryo (Fraser F., 1962) - 10,000 cases of infants with phocomelia due to thalidomide were reported; only 50% survived (Cuthbert A., 2001,2003). Grünenthal, a pharmaceutical company began marketing its new “wonder drug” as a sleeping pill and morning sickness preventative especially for pregnant women in 1957 as safe, though it had never tested the drug on pregnant animals not to mention in humans. EBM should ensure a more rigid process to guarantee safety and efficacy of medicinal drugs.|
|Materia medica is the Latin medical term for the body of collected knowledge about the therapeutic properties of any substance used for healing derived by the Ancient Greek physician Dioscorides in the 1st century AD (Ruggy G., 1946). The term materia medica was used from the period of the Roman Empire until the 20th century, but has now been generally replaced in medical education contexts by the term pharmacology.|
Turmeric, the ancient golden spice finally gets its well-deserved recognition
Turmeric derived from the rhizome of the plant Curcuma longa and has been used by the people of the Indian subcontinent for centuries with no known side effects, not only as a component of food but also to treat a wide variety of ailments (Aggarwal et al. 2006).
Today, turmeric is reaching new levels of awareness and respect. As is so often the case, extensive preclinical and clinical research on turmeric over the past few decades has confirmed most of its traditional uses. Modern medical findings include antioxidant, anti-inflammatory, anticancer, antigrowth, anti-arthritic, anti-atherosclerotic, antidepressant, anti-aging, antidiabetic, antimicrobial, wound healing, hepato-protective and memory-enhancing activities (Aggarwal et al., 2007; Aggarwal et al., 2013) which can be linked to its Ayurvedic actions described in the old texts of Charaka Saṃhitā (Table 1, Figure 1). From the traditional Ayurvedic point of view, turmeric is popular for its ability to balance all three constitutional dosha to a healthy equilibrium making it a mainstay of everyday health.
Table 1 Linking traditionally experienced properties of turmeric with modern science based medicine
|Sanskrit||Meaning||Potential uses of turmeric based on modern science**|
|Lekhanīya||’Scraping’ property||Gall stone, Hypolipidemia|
|Dīpana||Enkindles the digestive fire||Hypothyroidism|
|Prameha||Useful in diabetes||Diabetes|
|Pāṇḍughna||Used in Anaemia||Fanconi anemia|
|Raktaśodhana||Blood purifier||All inflammatory diseases eg. Arthritis, Inflammatory bowel disease, Pancreatitis, Allergy, Cancer, Gastric Ulcer|
|Viṣaghna||Destroys poisons||Malaria, Leishmaniasis, Antihelminthic|
|Kuṣṭhagna||Removes skin diseases||Psoriasis|
|Vedanāstahāpana||Analgesic||All painful diseases|
|Sandhānīya||Heals broken bones||Osteoporosis|
|Śirovirecana||Clearing stagnation from the head||Multiple sclerosis, Epilepsy, Alzheimer’s, Parkinson’s|
|Stanyaśodhaka||Purifies breast and breast milk|
*properties of turmeric experienced over 4000 years in Ayurvedic Medicine (Caraka Samhita) from Pole S., 2006
**Aggarwal BB et al., 2007.
Figure 1. Turmeric’s history goes back over 2000 years, to the heyday of Ayurveda. Sushruta Samhita, dating to about 200 BCE, recommends a turmeric ointment to relieve the effects of consuming poisoned food and for wound healing (Singh A., 2014). Turmeric’s efficacy and safety was monitored through simply observing. Turmeric is prevalent in both formulations and oils, these have been adapted and developed on experience. As we have just seen, analytical and clinical research dates back at least to Avicenna (around 1000 CE) (Moosavi J., 2009) and as experimentation, science and technology became established, laboratory analysis gained momentum. Chemical analysis has so far uncovered hundreds of thousands of natural plant compounds. There are approximately 235 compounds in turmeric (Aggarwal et al., 2013). By means of modern science based medical research, the benefits of turmeric are being confirmed and the mechanisms of its action more deeply understood.
Inflammation – the trigger of most diseases
The breakthrough in modern turmeric research likely occurred when its anti-inflammatory activity was demonstrated in 1971 by Arora et al. The effect of turmeric was comparable to that of hydrocortisone, a steroidal drug prescribed for the treatment of many inflammatory and allergic conditions (Arora et al, 1971).
As you would expect for such a ubiquitous health problem, the recognition of inflammation dates back to ancient times. As documented by Celsus, a Roman doctor in the 1st century CE, the ancients understood that the tissue response to injury gave rise to rubor (redness, due to hyperemia), tumor (swelling, caused by increased permeability of the microvasculature and leakage of protein into the interstitial space), calor (heat, associated with the increased blood flow and the metabolic activity of the cellular mediators of inflammation), and dolor (pain, in part due to changes in the perivasculature and associated nerve endings) (Masi S., 2014). In Ayurveda, inflammation is categorised according to its own specific anatomy, physiology and pathology involving the pitta dosha, and various tissues especially including the plasma rasa and blood rakta dhatu tissues.
Inflammation provides a unifying pathophysiological mechanism underlying many chronic diseases, including diabetes, cardiovascular disease, certain cancers and bowel diseases, dementia, arthritis, and osteoporosis. Common pathophysiologic scenarios apply to many of these diseases (Huang and Glass, 2010). Mastery of the inflammatory response should aid the prevention and treatment of these chronic diseases.
Does this explain why turmeric is a known therapeutic plant medicine for so many different diseases?
Taking a closer look: Whole spectrum of Turmeric rather than Curcumin
Turmeric is chemically diverse: so far approximately 235 compounds have been identified including polyphenolic, terpenes and volatile oils. Curcumin is just one compound that gives the yellow colour to turmeric (Aggarwal et al., 2006). It was first isolated two centuries ago and has been extensively studied in the last century. Early on in the clinical research into turmeric all of the activities ascribed to it were associated with curcumin. However, more recent studies have identified that curcumin-free turmeric components possess also numerous biological activities including anti-inflammatory, anticancer and antidiabetic activities (Aggarwal et al., 2013). This comes as no surprise to traditional medicine; turmeric, known as jiang huang in China, has long been used effectively as a water decoction in Traditional Chinese Medicine (TCM). As the non-polar curcumin is poorly absorbed in water the other compounds in turmeric would have to be responsible for its potent pain relieving properties for which it was used.
The analysis of a UK leading turmeric product (WTE) made from a whole turmeric extract including concentrated curcumin, essential oils and whole turmeric root in comparison with a UK leading concentrated 95% curcumin product (CE) demonstrates the health benefits of the whole spectrum of turmeric and also that it is not just about the curcumin. Brunswick Laboratories (U.S.) analysed the impact of WTE vs. CE on specific proteins in a human cell line study. Nrf2, NF-kB and COX-2 (please find more details in the box below) are naturally present in humans and have a key role in specific pathways, impacting inflammation, aging, pain and disease causation and prevention. The extent of the impact is dependent upon their activation levels, it’s like a dimming rheostat which could either be turned on to its full potential, switched off or anything in between. For example, in the case of Nrf2, a multi-organ protector, ideally it would be fully activated in the body as it reduces inflammation, supporting the detoxification process and activating antioxidant responses. Whereas NF-kB, a transcription factor which triggers inflammation, and COX-2, an enzyme responsible for swelling and inflammatory pains, would preferably be fully dimmed.
The study found that the activity of multi-organ protector Nrf2 is enhanced by 76% when treated with WTE. To achieve this level of activation with CE*, four times as much product must be used. Nrf2 truly deserves its name multi organ protector because it plays a vital role in cells. It maintains cellular homeostasis, detoxifies enzymes and reduces inflammatory responses, which is crucial for disease prevention, supporting the healing process and to slow aging. Especially important is Nrf2’s ability to limit cell exposure to chemical or oxidative stress, through regulation of antioxidant proteins.
The treatment with WTE shows an inhibition of NF-kB by 66% and this effect was 2.6 times more than that of CE**. Furthermore, COX-2 is inhibited by 60% when treated with WTE, with up to 10 times greater inhibition vs. CE and even 5.5 times better than paracetamol which is popular for its inhibition of COX-2***. In both cases, the dimming rheostat was turned down from 100% to 34% and 40% respectively, indicating that WTE reduces inflammation and pain significantly and more effectively than CE and paracetamol do.
A recently published study reports that Acetaminophen (Paracetamol) reduces people’s empathy for the pain of others. Paracetamol is an ingredient in over 600 different medications, including being the main constituent of Tylenol which is taken by a quarter of US adults each week. Dr. Dominik Mischkowski, the study’s first author said that the ubiquitous painkiller does not just kill pain, it also kills our fellow-feeling in two double-blind placebo-controlled experiments with 80 participants (Mischkowski et al.,2016).
However, these results are not surprising considering research which indicates curcumin-free turmeric is as effective as, or even more effective than isolated curcumin products (Aggarwal et al., 2006) showing that a WTE extract that combines the full spectrum of Turmeric’s 230 compounds is the most effective of them all.
There are several reasons why you should consider using the whole spectrum of turmeric rather than only the pure curcumin: turmeric contains more than 200 bioactive compounds which are beneficial to your health. None of this goodness is present in any simple curcumin products. By taking isolated curcumin, you would forego the benefits of turmerones (part of the essential oil) which not only significantly enhances the absorption and transport of curcumin but are proven to exhibit anti-inflammatory and anticancer activities and support regeneration in neurologic disease (Hucklenbroich et al. 2014).
|Nrf2, Nuclear factor (erythroid-derived 2)-like 2, is involved in cellular responses to oxidative damage triggered by injury and inflammation and plays a key role to manage various pathways and protects the various organs in the body as the name multi-organ protector already demonstrates.
Nrf2 is transcendental in the regulation of various cellular processes, such as antioxidant defences, redox equilibrium, the inflammatory process, the apoptotic processes, intermediate metabolism, detoxification, and cellular proliferation (Morales-González et al. 2015) and furthermore upregulating its activity is a strategy for cancer chemo-preventive phytochemicals (Becks et al. 2010). Numerous studies have shown this Nrf2-conferred, multi-organ protection phenomenon protects many cell types and organ systems from a broad spectrum of toxic insults and disease pathogenesis (Lee et al. 2005).
It was found that Nrf2 has an antagonistic effect on the NF-κB pathway (Cuadrado A. et al. 2014). When Nrf2 is activated, NF-kB pathways is also mediated and concurrently downregulated showing how such multiple interactions allow bioactive compounds, including turmeric, to exert their beneficial preventive and therapeutic effects.
|NF-kB (nuclear factor 'kappa-light-chain-enhancer' of activated B-cells), a protein complex that plays a key role in regulating the immune response to infection. Inhibition of NF-κB limits the production of pro-inflammatory gene expression and reduces the level of inflammation, therefore NF-κB has been studied as a biomarker for inflammation, and inhibition of NF-κB has been used as an indicator for anti-inflammatory potential.|
|COX-2(Cyclooxygenases-2 inhibitors) are among the important targets for treatment of inflammation related diseases. It is reported that selective COX-2 can target inflammation and pain with reduced risk of chronic ulceration and acute injury.|
Overwhelmed by choice – choosing the right one
With so much choice it is difficult to choose the right turmeric on the market. Here are some tips in making the correct decision. Buy whole turmeric root extracts with whole turmeric root instead of an isolated curcumin product, to make sure that you do not miss out any additional benefits from the multiple compounds in whole turmeric. I recommend taking an organic product, as you do not want to spoil the advantages of turmeric with harmful chemicals like pesticides that are so often used in growing conventional turmeric. Avoid dangerous chemical residues – such as hexane, methanol and acetone - from industrial curcumin extraction methods, gelatine – important to avoid for vegetarians and vegans - and harmful emulsifiers like polysorbate 80 (Tween 80) that have been tested in animals and are used to supposedly enhance curcumin’s bioavailablity 185 times. A recently published article in ‘Nature’ shows that Tween-80 has pro-inflammatory potential, leading to metabolic syndrome and promotes colitis and low-grade intestinal inflammation (Chassaing et al. 2014).
From Traditional to Modern Medicine…
Reflecting upon the information above – it is no wonder that turmeric has a long and safe history in disease prevention. Researchers are confirming the observations of our ancestors, thus inspiring health-conscious individuals. Isn’t it incredible that ancient knowledge dating back 4000 years, is suddenly validated by modern science? An advantage of knowing that turmeric has a long, safe and effective hsitory is the additional bonus of turmeric compared to newer modern pharmaceutical products, such as the NSAIDs and associated anti-inflammatories with their well document gastric and hepatotoxicity. Moreover, we are able to better understand the mechanisms of action for how the whole spectrum of turmeric is an efficient ally for so many different diseases. As we have seen, inflammation is a common trigger for many diseases and turmeric shows significant anti-inflammatory, analgesic and anti-swelling potential. From an Ayurvedic perspective, turmeric helps to balance all three dosha vāta, pitta and kapha, linking the dosha to pathophysiology we get the full picture: Inflammation = pitta-Aggravation, Pain = vāta Aggravation, Swelling = kapha Aggravation. Bringing all this together not only supports the benefits of turmeric with research but also links to the basic Ayurvedic principles simply observed in nature.
Key facts of research analysis in a human cell line
*6.6µg/mL of a UK leading whole spectrum turmeric product have the same impact on the anti-inflammatory multi-organ protector Nrf2 as 26µg/mL of a UK leading isolated curcumin product.
From cell line studies to human benefits
In vitro assays including enzymatic assays and cell-based assays have been used in pharmaceutical industry for decades as an intermediate step towards drug discovery. The final approval and demonstration of the health benefits/biological relevance of course is done by clinical studies, but the in vitro assays help to guide the product formulators towards successful products that would show clinical significance.
Aggarwal B.B, Ichikawa H., Garodia P., Weerasinghe P., Sethi G., Bhatt I.D., Pandey M.K., Shishodia S., Nair M.G. From traditional Ayurvedic medicine to modern medicine: identification of therapeutic targets for suppression of inflammation and cancer. Expert Opin Ther Targets 2006;10(1):87-118.
Aggarwal B.B., Sundaram C., Malani N., Ichikawa H. Curcumin: the Indian solid gold. Adv Exp Med Biol. 2007;595:1-75.
Aggarwal B.B., Yuan W., Li S., Gupta S.C. Curcumin-free turmeric exhibits anti-inflammatory and anticancer activities: Identification of novel components of turmeric. Mol Nutr Food Res. 2013;57(9):1529-42.
Arora, R. B., Kapoor, V., Basu, N., Jain, A. P. Anti-inflammatory studies on Curcuma longa (turmeric). Indian J. Med. Res. 1971, 59, 1289–1295.
Becks L, Prince M, Burson H, Christophe C, Broadway M, Itoh K, Yamamoto M, Mathis M, Orchard E, Shi R, McLarty J, Pruitt K, Zhang S, Kleiner-Hancock HE. Aggressive mammary carcinoma progression in Nrf2 knockout mice treated with 7,12-dimethylbenz[a]anthracene. BMC Cancer 2010;8(10):540.
Chassaing B., Koren O., Goodrich J.K., Poole A.C., Srinivasan S., Ley R.E., Gewirtz A.T. Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome. Nature. 2015, 519(7541):92-6.
Cuadrado A., Martín-Moldes Z., Ye J., Lastres-Becker I. Transcription factors NRF2 and NF-κB are coordinated effectors of the Rho family, GTP-binding protein RAC1 during inflammation. J Biol Chem. 2014; 30;289(22):15244-58.
Cuthbert, Alan (2001, 2003). The Oxford Companion to the Body. Oxford University Press. Retrieved 26 February 2012.
Echt D.S., Liebson P.R., Mitchell L.B., Peters R.W., Obias-Manno D., Barker A.H., Arensberg D., Baker A., Friedman L., Greene H.L., et al. Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial. N Engl J Med. 1991; 21;324(12):781-8.
Fraser F.C. Drug-induced teratogenesis. Can Med Assoc J. 1962;29;87:683-4.
Huang W. and Glass C. Nuclear receptors and inflammation control: molecular mechanisms and pathophysiological relevance. Arterioscler Thromb Vasc Biol. 2010; 30(8): 1542–1549.
Hucklenbroich J., Klein R., Neumaier B., Graf R., Fink G., Schroeter M. Rueger M. Aromatic-turmerone induces neural stem cell proliferation in vitro and in vivo. Stem Cell Res Ther. 2014;26;5(4):100).
Jaeschke R., Guyatt G. What Is Evidence-Based Medicine? Seminars in Medical Practice 1999,2(3), 3-7.
Lazarou J., Pomeranz B., Corey P.N. Incidence of adverse drug reactions in hospitalized patients: A metaanalysis of prospective studies. JAMA, 1998; 279: 1200–1205.
Lee JS, Surh YJ. Nrf2 as a novel molecular target for chemoprevention. Cancer Lett. 2005; 28;224(2):171-84.
Masi S. Leukocyte telomere length, inflammation and age-related diseases. Doctoral Thesis, Faculty of Medicine, University of London, Vascular Physiology Unit Institute of Cardiovascular Science University College London, 2014, page 49.
Mischkowski D., Crocker J. and Way B.M. From Painkiller to Empathy Killer: Acetaminophen (Paracetamol) Reduces Empathy for Pain. Soc Cogn Affect Neurosci 2016;
Morales-González JA, Madrigal-Santillán E, Morales-González Á, Bautista M, Gayosso-Islas E, Sánchez-Moreno C. What is Known Regarding the Participation of Factor Nrf-2 in Liver Regeneration? Cells 2015;4(2):169-77.
Moosavi J. The Place of Avicenna in the History of Medicine. Avicenna J Med Biotechnol. 2009; 1(1): 3–8.
Narayanaswamy V. Origin and Development of Ayurveda (A brief history). Ancient Science of Life. 1981; 1 (1); 1-7 V.
Packer M., Carver J.R., Rodeheffer R.J., Ivanhoe R.J., DiBianco R., Zeldis S.M., Hendrix G.H., Bommer W.J., Elkayam U., Kukin M.L., et al. Effect of oral milrinone on mortality in severe chronic heart failure. The PROMISE Study Research Group. N Engl J Med. 1991; 21;325(21):1468-75.
Pole S. Ayurvedic Medicine: The Principles of Traditional Practice 2006, ISBN: 978-1-84819-113-6, pages XVII, 24-27, 282.
Sackett D, Rosenberg W., Gray M., Haynes B., Richardson S. Evidence based medicine: what it is and what it isn't. BMJ 1996;312:71-72.
Singh A., Singh A.K., Narayan G., Singh T.B., Shukla V.K. Effect of Neem oil and Haridra on non-healing wounds. Ayu. 2014;35(4):398-403.
The EC/IC Bypass Study Group. Failure of extracranial-intracranial arterial bypass to reduce the risk of ischemic stroke. Results of an international randomized trial. N Engl J Med. 1985;7;313(19):1191-200.
Wang J.H. Historical Timeline of Chinese Medicine; Understanding the Past http://www.traditionalstudies.org/historical-timeline-of-chinese-medicine/ Retrieved 15 May 2016.
Upton R.H. Traditional Herbal Medicine, Pharmacognosy, and Pharmacopoeial Standards: A Discussion at the Crossroads (2015) in Evidence-Based Validation of Herbal Medicine edited by Mukherjee. ISBN 987-0-12-800874-4. http://dx.doi.org/10.1016/B978-0-12-800874-4.00003-9.