What is Sandalwood

Sandalwood is the general name for woody perennials of the Santalum genus (Santalaceae), which are exploited for their fragrant heartwood. Sandalwoods are slow growing hemiparasitic trees distributed throughout the tropical and temperate regions of India, Indonesia, Australia and the Pacific Islands ¹. The oil extracted from the sandalwood tree stems and roots are highly sought after by the fragrance and perfume industry. Santalum album, also known as tropical or Indian sandalwood, is the most valuable of the commercially used species due to the high heartwood oil content (6–10% by dry weight) and desirable odor characteristics. Approximately 90% of Sandalwood essential oil is composed of the sesquiterpene alcohols α-, β-, and epi-β-santalol and α-exo-bergamotol. The α- and β-santalols are the most important contributors to sandalwood oil fragrance ². Lanceol and α-bisabolol are also found in modest concentrations ³. While the demand for sandalwood oil is increasing, disease, grazing animals and unsustainable exploitation of sandalwood trees has led to the demise of many natural populations. Plantations provide a more sustainable alternative to wild harvesting; however, slow growth rates, high potential for disease and substantial variation in oil yield hamper productivity. Alternatively, chemical approaches to synthesize the santalols have been attempted ⁴, key to these approaches is the elucidation of the biosynthesis of the santalols, bergamotols, and other sesquiterpene compounds characteristic of sandalwood oil. But multiple low-recovery steps make chemical synthesis uneconomical at an industrial scale.

Figure 1. Sandalwood

Sandalwood essential oil

Indian sandalwood (Santalum album L.) is an economically important plant species because of its ability to produce highly valued perfume oils. Sandalwood oil is an essential oil obtained from the steam distillation of chips and billets cut from the mature heartwood of various species of sandalwood trees – the most common are the Indian sandalwood (Santalum album) and Australian sandalwood (Santalum spicatum) followed by the species found in Hawaii (Santalum ellipticum), New Caledonia (Santalum austrocaledonicum), and French Polynesia (Santalum insulare) ⁵.  The chemical composition of sandalwood essential oil has been studied in detail. At least 300 chemical constituents have been identified. The essential oil obtained from the well matured sandalwood tree is represented by a mixture of sesquiterpene olefins and alcohols such as: (Z)-α-santalol, (Z)-β-santalol, (Z)-epi-β-santalol, (Z)-α-trans-bergamotol, α-bisabolol, (Z)-lanceol, sesquisabinene hydrate and (E,E)-farnesol, along with small amounts (up to 2%) of corresponding precursor sesquiterpene hydrocarbons ⁶. Four sesquiterpenols, α-, β-, and epi-β-santalol and α-exo-bergamotol, make up approximately 90% of the oil of Indian sandalwood, where (Z)-α-santalol (alpha-santalol) and (Z)-β-santalol (beta-santalol) constitute the most abundant ⁷ and the major active components ⁸.

Table 1. Chemical composition of New Caledonia Sandalwood (Santalum austrocaledonicum) essential oil

Sandalwood essential oil is widely used for several purposes such as in perfumery, cosmetics, aromatherapy, as an antidepressant, anti-inflammatory, antifungal, astringent, sedative, insecticide, antiseptic and in sacred unguents ¹⁰, ¹¹. Sandalwood essential oil is also used in the food industry as a flavoring ingredient with a daily consumption of 0.0074 mg/kg ¹². Sandalwood oil and its major constituent have low acute oral and dermal toxicity in laboratory animals ¹². Although the available information on toxicity of sandalwood oil is limited, it has a long history of oral use without any reported adverse effects and is considered safe at present use levels ¹².

Sandalwood essential oil uses

Sandalwood essential oil is used in perfumes, cosmetics, sacred unguents, and as a mild food flavoring. Due to its highly coveted fragrance, the essential oil produced from Sandalwood is often used in aromatherapy and is added to soaps and cosmetics. It is also used in Ayurvedic medicine for the treatment of both somatic and mental disorders, including common colds, bronchitis, fever, urinary tract infections, and inflammation ¹³. A study investigating the effects of inhalation of East Indian sandalwood oil and its main compound, α-santalol, on human physiological parameters found that the compounds elevated pulse rate, skin conductance, and systolic blood pressure ¹³.

Sandalwood essential oil has also been studied as a chemopreventive agent for skin papillomas in mice ¹⁴ and in vitro in human epidermoid carcinoma cells ¹⁵. Matsuo and Mimaki studied the cytotoxicity of various α-santalol derivatives and found that some of them present tumor-specific cytotoxicity ¹⁶. This group also found that α-santalol induces DNA fragmentation as a result of apoptosis ¹⁶. Even though previous studies have provided valuable data on the pharmacological properties of individual constituents of sandalwood essential oil, there is no information on the activity of whole sandalwood essential oil in human breast cells, or on its DNA-damaging potential. Due to the increased popularity of essential oils for massage and aromatherapy, people are frequently exposed to sandalwood essential oil through various routes of administration including the skin. Essential oils can easily be absorbed through the human skin due to their lipid solubility and extremely low molecular size and the lipophilic nature of the skin itself ¹⁷.

Folk medicine uses

Sandalwood has been used in traditional medicine and Ayurveda to treat many conditions such as:

• Lymphatic system – Venous and lymphatic stasis such as varicose veins and swollen lymph nodes.
• Nervous system – Sandalwood oil has a relaxing effect on the nerves and may be used for hot, agitated emotional states leading to conditions such as headaches, insomnia and nervous tension.
• Respiratory system – Can treat respiratory tract infections, especially when its soothing, demulcent effects are required.
• Genitourinary – Has been used for years for genitourinary tract infections (e.g. Cystitis and gonorrhoea). “Sandalwood is an astringent and helps to resolve mucous congestion. Sandalwood oil helps to restore the mucous membrane and minimise the risk of infection”
• Integumentary system– “Applied to the skin, sandalwood oil is soothing, cooling and moisturising and primarily used for dry skin conditions caused by loss of moisture and skin inflammations. It may be used to relieve eczema and psoriasis and for the treatment of oily skin and acne”
• Anti-viral(herpes simplex/cold sores)
• Anti-cancer e.g. skin cancer, breast cancer
• Anti-microbial
• Anti-fungal

Summary

Our take is that sandalwood and sandalwood essential oil uses lack proper clinical scientific evidence to be of any use apart for its use in the food flavoring and perfumery industry. More studies especially well designed human clinical trials are needed to substantiate these pseudo-science or anecdotal therapeutic effects or benefits.

1. Geographic and phenotypic variation in heartwood and essential-oil characters in natural populations of Santalum austrocaledonicum in Vanuatu. Page T, Southwell I, Russell M, Tate H, Tungon J, Sam C, Dickinson G, Robson K, Leakey RR. Chem Biodivers. 2010 Aug; 7(8):1990-2006. https://www.ncbi.nlm.nih.gov/pubmed/20730962/[↩]
2. Baldovini N, Delasalle C, Joulain D (2011) Phytochemistry of the heartwood from fragrant Santalum species: a review. Flavour Fragrance J 26: 7–26[↩]
3. Jones CG, Plummer JA, Barbour EL (2007) Non-destructive sampling of Indian sandalwood (Santalum album L.) for oil content and composition. J Essent Oil Res 19: 157–164[↩]
4. Brocke C, Eh M, Finke A (2008) Recent developments in the chemistry of sandalwood odorants. Chem Biodivers 5: 1000–1010. https://www.ncbi.nlm.nih.gov/pubmed/18618410[↩]
5. Phylogeny and biogeography of the sandalwoods (Santalum, Santalaceae): repeated dispersals throughout the Pacific. Harbaugh DT, Baldwin BG. Am J Bot. 2007 Jun; 94(6):1028-40. http://www.amjbot.org/content/94/6/1028.long[↩]
6. Preparative separation of α- and β-santalenes and (Z)-α- and (Z)-β-santalols using silver nitrate-impregnated silica gel medium pressure liquid chromatography and analysis of sandalwood oil. Daramwar PP, Srivastava PL, Priyadarshini B, Thulasiram HV. Analyst. 2012 Oct 7; 137(19):4564-70. https://www.ncbi.nlm.nih.gov/pubmed/22900258/[↩]
7. Structure-odor relationships of α-santalol derivatives with modified side chains. Hasegawa T, Izumi H, Tajima Y, Yamada H. Molecules. 2012 Feb 22; 17(2):2259-70.[↩]
8. Phylogeny and biogeography of the sandalwoods (Santalum, Santalaceae): repeated dispersals throughout the Pacific. Harbaugh DT, Baldwin BG. Am J Bot. 2007 Jun; 94(6):1028-40.[↩]
9. Ortiz C, Morales L, Sastre M, Haskins WE, Matta J. Cytotoxicity and Genotoxicity Assessment of Sandalwood Essential Oil in Human Breast Cell Lines MCF-7 and MCF-10A. Evidence-based Complementary and Alternative Medicine : eCAM. 2016;2016:3696232. doi:10.1155/2016/3696232. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4879231/[↩]
10. Jirovetz L. et al. Comparative study on the antimicrobial activities of different sandalwood essential oils of various origin. Flavour Frag. J. 21, 465–468 (2006).[↩]
11. Chemopreventive effects of various concentrations of alpha-santalol on skin cancer development in CD-1 mice. Dwivedi C, Maydew ER, Hora JJ, Ramaeker DM, Guan X. Eur J Cancer Prev. 2005 Oct; 14(5):473-6.[↩]
12. Safety assessment of sandalwood oil (Santalum album L.). Burdock GA, Carabin IG. Food Chem Toxicol. 2008 Feb; 46(2):421-32. https://www.ncbi.nlm.nih.gov/pubmed/17980948/[↩][↩][↩]
13. East Indian Sandalwood and alpha-santalol odor increase physiological and self-rated arousal in humans. Planta Med. 2006 Jul;72(9):792-800. Epub 2006 Jun 19. https://www.ncbi.nlm.nih.gov/pubmed/16783696[↩][↩]
14. Sandalwood oil prevent skin tumour development in CD1 mice. Dwivedi C, Zhang Y. Eur J Cancer Prev. 1999 Oct; 8(5):449-55.[↩]
15. Skin cancer chemopreventive agent, {alpha}-santalol, induces apoptotic death of human epidermoid carcinoma A431 cells via caspase activation together with dissipation of mitochondrial membrane potential and cytochrome c release. Kaur M, Agarwal C, Singh RP, Guan X, Dwivedi C, Agarwal R. Carcinogenesis. 2005 Feb; 26(2):369-80. https://www.ncbi.nlm.nih.gov/pubmed/15528219/[↩]
16. α-Santalol derivatives from Santalum album and their cytotoxic activities. Matsuo Y, Mimaki Y. Phytochemistry. 2012 May; 77():304-11. https://www.ncbi.nlm.nih.gov/pubmed/22410352/[↩][↩]
17. Keville K., Green M. Aromatherapy: A Complete Guide to the Healing Art. Freedom, Calif, USA: The Crossing Press; 1995. The sense of smell; pp. 9–10.[↩]

What is spearmint

Spearmint (Mentha spicata) family Lamiaceae is a herbaceous rhizomatous perennial plant growing 30–100 cm tall, with variably hairless to hairy stems and foliage, and a wide-spreading fleshy underground rhizome ¹. Spearmint is also known as garden mint, common mint, lamb mint and mackerel mint ². Spearmint leaves are 5–9 cm long and 1.5–3 cm broad, with a serrated margin. The stem is square-shaped, a trademark of the mint family of herbs. Spearmint produces flowers in slender spikes, each flower pink or white and 2.5–3 mm long and broad. Spearmint is a species of mint native to much of Europe and Asia (Middle East, Himalayas, China etc.) and naturalized in parts of northern and western Africa, North America, and South America, as well as various oceanic islands.

Spearmint leaves are popularly used as a tea flavoring agent. Spearmint is also often used in Indian and Italian cuisine and usually added fresh or dried to fish and shellfish plates before or after cooking.

The fresh and dried spearmint leaves and their essential oils are widely used in the food, cosmetic, confectionary, chewing gum, toothpaste, and pharmaceutical industries ³. Spearmint are extensively used as flavoring in confectionery and food industries and fragrance industries, pharmaceutical preparations and cosmetic products and also in hygiene products ⁴.  ⁵.

Figure 1. Spearmint

Spearmint essential oil

The composition of the essential oil of spearmint (M. spicata) is presented in Table 1. There is large variation in the chemical composition of spearmint, wild as well as cultivated, around the world. The differences in oil content and composition may be attributed to factors related to ecotype, phenophases, temperature, relative humidity, photoperiod, irradiance, genotype, and agronomic conditions (harvesting time, plantage, crop density). In the north Indian plains carvone content varies between 45.9% and 77.1% ⁶. The percentage of carvone also varies in the essential oil of spearmint growing in different countries, e.g., Egypt (46.4%–68.55%) ⁷, Canada (59%–74%) ⁸, Colombia (61.53%) ⁹; Turkey (78.35%–82.2%) ¹⁰, China (55.45%–74.6% ¹¹, Bangladesh (73.2%) ¹², Algeria (59.4%) ¹³, and Morocco (29%) ¹⁴. Lower amounts of carvone were reported in the spearmint essential oil from Iran (22.4%) ¹⁵. Carvone-rich essential oils are widely used as spices in the flavor and fragrance industries in Europe ¹⁶.

Table 1. Components of the Spearmint essential oils (Mentha spicata)

Spearmint essential oil uses

Spearmint oil is the essential oil extracted from the flowering tops of Mentha spicata. Spearmint oil is used for its aromatic properties and for treatment of illnesses of the digestive and respiratory systems. Spearmint possesses several biological activities and is used in folkloric medicine for relieving flatulence, antispasmodic, diuretic, antibacterial, antifungal, and antioxidant agent, and for treatment of colds and flu, respiratory tract problems, gastralgia, hemorrhoids, and stomachache ¹⁸.

Some studies have been shown that spearmint oil has anti-fungal, anti-microbial, anti-inflammatory, anti-tumor and antioxidant activity ¹⁹.

The major constituents of spearmint leaves essential oil are carvone (29–74%), limonene (4–24%), dihydrocarvone, 1,8-cineol, β-bourbonene, β-caryophyllene, myrcene and α-pinene and aromatherapists. Spearmint is mainly recommended for its antispasmodic effects, which are related to its carvone content, the most important constituent of spearmint. Spearmint oil is also used for its local anesthetic, astringent, carminative, decongestant, digestive, diuretic and expectorant effects ²⁰, ²¹. Furthermore, various beneficial medicinal effects of spearmint have been found, such as preventing chemotherapy-induced nausea and vomiting ²², treatment of respiratory and digestive system disorders, hypertension, anxiety and even for relieving menstrual pain ²³.

Antioxidant Activity of spearmint essential oil

Four antioxidant assays have been used to evaluate the possible antioxidant properties of the spearmint essential oil, including (1,1-diphenyl-2-picrylhydrazyl scavenging activity) DPPH radical scavenging activity, superoxide anion scavenging, reducing power, and antioxidant assay using β-carotene linoleate system. The results obtained confirm previous reports about the importance of essential oils as natural antioxidants and their possible role in the protection of human health. Organic extracts of spearmint species have been found to have antioxidant and antiperoxidant properties due to the presence of eugenol, caffeic acid, rosmarinic acid, and α-tocopherol ²⁴. An aqueous extract of peppermint provides protection against radiation-induced chromosomal damage in the bone marrow of mice by decreasing serum acid phosphatase and increasing serum alkaline phosphatase ²⁵.

Recently, Naidu et al. ²⁶ reported that the total phenolic component of a crude methanolic extract of spearmint was found to be 27.26 ± 0.62 mg/g gallic acid equivalent. The (1,1-diphenyl-2-picrylhydrazyl scavenging activity) DPPH radical scavenging activity was found to increase with increasing concentrations and was found to be 54.84% ± 0.57% with an IC50 value of 25.2 µg/mL. In the same year, Martins et al. ²⁷ studied the chemical composition and antioxidant activities of spearmint essential oil harvested from Portugal and reported the identification of 30 components that constitute 87.7% of the total composition. Oxygenated monoterpenes (46.3%), monoterpene hydrocarbons (25.5%), and sesquiterpene hydrocarbons (14.1%) were found to be the major constituent groups, with the monoterpere carvone (41.1%) as the main constituent. This essential oil showed antioxidant activity both by (1,1-diphenyl-2-picrylhydrazyl scavenging activity) DPPH radical scavenging method (31.45%) and by system β-carotene/acid linoleic method (14.89%).

Antibacterial activity of spearmint essential oil

The antibacterial activity of spearmint essential oil tested against 30 Vibrio spp. microorganisms was examined both qualitatively (inhibition zone diameter) and quantitatively (MIC and MBC values). Moreover, its potency to inhibit and eradicate the biofilm formed on polystyrene surface (XTT assay) was tested in the a study ¹. The results showed that the studied spearmint essential oil had substantial anti-Vibrio spp. activity.

The results of another study ²⁸ indicated that spearmint essential oil has remarkable antibacterial activity against common food-borne bacteria associated with outbreaks (S. aureus, B. subtilis, B. cereus, L. monocytogenes, S. typhimurium, and E. coli O157:H7). The antibacterial activity of the essential oil could be attributed to the presence of various active compounds. The main components were carvone (78.76%), limonene (11.50%), β-bourbonene (11.23%), cis-dihydrocarveol (1.43%), trans-caryophyllene (1.04%), menthone (1.01%), menthol (1%), and terpinen-4-ol (0.99%).

Uribe et al. ²⁹ reported that monoterpenoids such as (R-) and (S-) carvones exert an antimicrobial effect by interacting with the microbial membrane due to their inherent lipophilicity, while, the combination of R- and S-carvone suggested that carvones have a high affinity for the bacterial cell membrane and may influence structural or functional properties of the membrane ³⁰. In fact, using the Transmission Electron Microscope, Mun and colleagues ³¹ revealed cytoplasmic disruption and separation of the cytoplasmic contents of methicillin-resistant S. aureus strains following exposure to R-carvone. Additionally, (4R)-(−)-carvone was also active against Campylobacter jejuni, Enterococcus faecium, Escherichia coli, and Aspergillus niger ³², while (4S)-(+)-carvone was effective against E. coli O157:H7, Salmonella typhimurium Photobacterium leiognathi, and Listeria monocytogenes ³². In a previous work carried out by Aggarwal et al. ³³, the results showed that the main components found in spearmint oil were (4S)-(−)-limonene, (4R)-(−)-carvone), (R)-(+)-limonene, and (4S)-(+)-carvone) for A. sowa Roxb essential oil. They also found that both optical isomers of carvone were active against a wide spectrum of human pathogenic fungi and bacteria. Additionally, the antimicrobial properties of these monoterpenes were similar to those in spearmint and Indian dill essential oils.

Spearmint vs Peppermint

Peppermint (Mentha x piperita, also known as Mentha balsamea Willd) is a hybrid mint, a cross between watermint and spearmint ³⁴. Indigenous to Europe and the Middle East, the plant is now widespread in cultivation in many regions of the world. It is occasionally found in the wild with its parent species.

Peppermint oil has a high concentration of natural pesticides, mainly pulegone (found mainly in Mentha arvsis var. piperascens cornmint, field mint, Japanese mint, and to a lesser extent in Mentha piperita subsp. nothosubsp. piperita) and menthone. It is known to repel some pest insects, including mosquitos, and has uses in organic gardening.

The major constituents of peppermint are menthol (30–55%) and menthone (14–32%). Menthol occurs mostly in the free alcohol form, with small quantities as
the acetate (3–5%) and valerate esters. Other monoterpenes present include isomenthone (2–10%), 1,8-cineole (6–14%), a-pinene (1.0–1.5%), b-pinene (1–2%), limonene (1–5%), neomenthol (2.5–3.5%) and menthofuran (1–9%).

Medicinal uses of peppermint supported by clinical data for symptomatic treatment of irritable bowel syndrome ³⁵ and digestive disorders such as flatulence and gastritis ³⁶. Externally for treatment of myalgia and headache ³⁷.

Figure 2. Peppermint (Mentha piperita)

Table 2. Components of the Peppermint essential oils (Mentha x piperita)

Spearmint side effects

There is some evidence which show that despite spearmint beneficial effects, spearmint has some toxic and adverse effects. Severe histopathological changes in kidney, liver and uterus tissue ³⁸ and also contact allergic reaction to the leaves of spearmint have been reported. Furthermore, daily consumption of four cups of spearmint tea can diminish libido in men ³⁹. In one study, Akdogan ⁴⁰ showed that spearmint herbal tea has adverse effects on testicular tissue and testosterone level, and alters the level of follicular stimulating hormone (FSH) and luteinizing hormone (LH) in male rats ⁴¹. Akdogan and colleagues ⁴² studied 21 females with hirsutism (12 with polycystic ovary syndrome and 9 with idiopathic hirsutism) drank a cup of herbal tea steeped with spearmint twice daily for 5 days during the follicular phases of their menstrual cycles. After treatment with the spearmint tea, the patients had significant decreases in free testosterone with increases in luteinizing hormone (LH), follicle-stimulating hormone (FSH) and estradiol ⁴². There were no significant decreases in total testosterone or DHEAS levels. This study was followed by a randomized clinical trial by Grant ⁴³, which showed that drinking spearmint tea twice daily for 30 days (vs. chamomile tea, which was used as a control) significantly reduced plasma levels of free and total testosterone in patients with hirsutism associated with polycystic ovarian syndrome (PCOS). LH and FSH also increased. There was a significant change in patients’ self-reported dermatology-related quality of life indices, but no objective change on the Ferriman-Gallwey scale. Therefore, people who consume spearmint should be advised to use this herbal plant in a proper manner and avoid high dose (the actual spearmint dosage has not been clarified). Furthermore, because the exact constituents of spearmint which cause antifertility have not been clarified, scientists suggest that ongoing studies should be performed on different fractions of spearmint extract.

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32. Friedman, M.; Henika, P.R.; Mandrell, R.E. Bactericidal activities of plant essential oils and some of their isolated constituents against Campylobacter jejuni, Escherichia coli, Listeria monocytogenes, and Salmonella enterica. J. Food Protect. 2002, 65, 1545–1560.[↩][↩]
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38. The effect of Mentha spicata Labiatae on uterine tissue in rats. Güney M, Oral B, Karahanli N, Mungan T, Akdogan M. Toxicol Ind Health. 2006 Sep; 22(8):343-8.[↩]
39. Effect of spearmint (Mentha spicata Labiatae) teas on androgen levels in women with hirsutism. Akdoğan M, Tamer MN, Cüre E, Cüre MC, Köroğlu BK, Delibaş N. Phytother Res. 2007 May; 21(5):444-7.[↩]
40. Effects of peppermint teas on plasma testosterone, follicle-stimulating hormone, and luteinizing hormone levels and testicular tissue in rats. Akdogan M, Ozguner M, Kocak A, Oncu M, Cicek E. Urology. 2004 Aug; 64(2):394-8. https://www.ncbi.nlm.nih.gov/pubmed/15302514/[↩]
41. Spearmint induced hypothalamic oxidative stress and testicular anti-androgenicity in male rats – altered levels of gene expression, enzymes and hormones. Kumar V, Kural MR, Pereira BM, Roy P. Food Chem Toxicol. 2008 Dec; 46(12):3563-70. https://www.ncbi.nlm.nih.gov/pubmed/18804513/[↩]
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What is spikenard

Spikenard, also called nard, nardin, and muskroot, is a class of aromatic amber-colored essential oil derived from Nardostachys jatamansi – commonly referred to as Indian spikenard, a flowering plant of the Valerian family which grows to about 10–60 m in height in the Himalayas of Nepal, China, and India ¹, ². There are several varieties of Spikenard, they are California spikenard (Aralia californica), Japanese spikenard (Aralia cordata) and American spikenard (Aralia racemosa). The underground stems of Spikenard can be crushed and distilled into an intensely aromatic amber-colored essential oil, which is very thick in consistency ³. Spikenard roots and rhizomes are harvested throughout the Himalayas and traded from the alpine regions to the plains of India. Spikenard roots are considered aromatic, bitter tonic, antispasmodic, deobstruent, stimulant, antiseptic, diuretic, and emmenagogue (stimulates or increases menstrual flow) ⁴. The roots of the plant were also used traditionally for indurations (lumps) and solid tumours in different systems of medicine ⁵. Bhagat et al., have reported the cytotoxicity of alcoholic extract and n-butanol fraction of spikenard in lung, liver, ovary and prostate cancer cell lines ⁶. Spikenard has been suggested to protect cells and tissues through its antioxidative properties ⁷. Moreover, two new sesquiterpenoids have been isolated from the roots and rhizomes of spikenard and cytotoxicity of the crude chloroform:methanol extract and the isolates have been studied in lung, prostate, estrogen receptor-positive breast cancer and neuroblastoma cell lines ⁸.

Previous studies also reported that the dried roots of spikenard contain sesquiterpenes, like jatamansone, spirojatamol, patchouli alcohol, norseychelanone, jatamol A and B, lignans and neolignans, like virolin, pinoresinol, jatamansic acid, and terpenic coumarins, like oroselol and jatamansin. Spikenard essential oil is composed of sesquiterpenoids and coumarins. Jatamansone is the principle sesquiterpenoid and is attributed with rendering majority of the biological activity ⁹.

Spikenard oil is used as a perfume, an incense, a sedative, and a herbal medicine said to fight insomnia, birth difficulties, and other minor ailments. A hexane extract of spikenard contained a lot of calarene and its vapor inhalation containing sesquiterpenoid aristolen-1(10)-en-9-ol had a sedative effect on mice ¹⁰, ¹¹. Spikenard oil has, since ancient times, been used as a perfume, as a medicine and in religious contexts, across a wide territory from India to Europe.

Figure 1. Spikenard plant

Spikenard uses

Spikenard has a long history of medicinal use which dates back to 1000–800 B.C. in Ayurveda and Unani systems of medicine for neurological disorders ¹². Spikenard roots (rhizomes) are rich in sesquiterpenoids, terpenic coumarins, phenols, flavonoids, alkaloids, lignans, and neo-lignans ¹³. It has been used as a sedative, promotion of sleep, antidepressant, antiepileptic, antihysteric, hypotensive, antispasmodic, anti-inflammatory, cardiotonic, for mind rejuvenation, alleviating mental diseases and as a brain tonic ¹⁴, ¹⁵. It has also been used for treating headache, insomnia, epilepsy; disorders of cardiovascular system; flatulence and intestinal colic as well as menopausal symptoms ¹⁴. Spikenard has been shown to possess anti-inflammatory ¹⁶, anti-oxidant ¹⁷, anti-bacterial ¹⁸, anticonvulsant ¹⁹ and hepatoprotective activities ²⁰. Spikenard has been shown to exhibit anti-tumour activity in lung, liver, ovary, breast and prostate cancers ¹⁹, ¹⁷. Recently, the higher doses of alcoholic and n-hexane extract of spikenard were shown to significantly inhibit the growth of neurobalstoma cell lines, IMR 32 and SK-N-SH ¹⁷.

Summary

Despite Spikenard long history of use in Ayurveda and traditional medicine, there is INSUFFICIENT clinical evidence to support its use as antioxidant, anti-cancer, anticonvulsant, anti-inflammatory, antidepressant, antihysteric, anti-hypertensive, antispasmodic, cardiotonic, for mind rejuvenation, alleviating mental diseases or even as a brain tonic. Good quality human trials are needed to establish whether or not there is therapeutic effect of Spikenard or Spikenard essential oil. Without such evidence, it will remain unclear whether these untested and unproven positive effects in test tube and animal studies are truly beneficial in humans.

1. Chauhan RS, Kaul MK, Kumar A, Nautiyal MC. Pollination behaviour of Nardostachys jatamansi DC., an endangered medicinal and aromatic herb. Sci Hortic-Amsterdam. 2008;117:78–81. doi: 10.1016/j.scienta.2008.03.018. [↩]
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8. Two new sesquiterpenoids from the rhizomes of Nardostachys jatamansi. Rekha K, Rao RR, Pandey R, Prasad KR, Babu KS, Vangala JR, Kalivendi SV, Rao JM. J Asian Nat Prod Res. 2013; 15(2):111-6.[↩]
9. Hoerster H., Ruecker G., Tautges J. Valeranone content in the roots of Nardostachys jatamansi and Valeriana officinalis. Phytochem. 1977;1:1070–1071. doi: 10.1016/S0031-9422(00)86735-7.[↩]
10. Inhalation administration of the sesquiterpenoid aristolen-1(10)-en-9-ol from Nardostachys chinensis has a sedative effect via the GABAergic system. Planta Med. 2015 Mar;81(5):343-7. doi: 10.1055/s-0035-1545725. Epub 2015 Mar 23. https://www.thieme-connect.com/DOI/DOI?10.1055/s-0035-1545725[↩]
11. Sedative effects of vapor inhalation of agarwood oil and spikenard extract and identification of their active components. Journal of Natural Medicines January 2008, Volume 62, Issue 1, pp 41–46. https://doi.org/10.1007/s11418-007-0177-0[↩]
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What is thyme

Thyme (Thymus vulgaris) is an aromatic perennial evergreen herb of the genus Thymus of the mint family (Lamiaceae) and a relative of the oregano genus Origanum – with culinary, medicinal, and ornamental uses. The genus Thymus has numerous species of about 350 species of perennial, aromatic herb and sub shrubs native to Europe and North Africa ¹. Various species of thyme is used all over the globe as condiments, ornamentals and sources of essential oil ². The essential oil of thyme or oil of thyme, contains 20–54% thymol, is utilized as a flavor enhancer in a wide variety of foods, beverages, confectionery products and in perfumery for the scenting of soaps and lotions ³. Thyme essential oil also contains a range of additional compounds, such as p-cymene, myrcene, borneol, and linalool.

Thymol is a phenol obtained from thyme oil, is used as a stabilizer in pharmaceutic preparations. Thymol has been used for its antiseptic, bronchiolytic, antibacterial, and antifungal actions, and was formerly used as a anti-parasitic worms medicine (vermifuge) that make it popular as a medicinal herb and as a preservative for foods ⁴. Thymol, an antiseptic, is an active ingredient in various commercially produced mouthwashes such as Listerine ⁵. Before the advent of modern antibiotics, oil of thyme was used to medicate bandages. Thymol can also be found as the active ingredient in some all-natural, alcohol-free hand sanitizers.

Figure 1. Fresh thyme

Table 1. Composition of the essential oils of Thyme (Thymus vulgaris)

Note: The main components were thymol (48.9%) and p-cymene (19.0%)

Thyme uses

Culinary use

Thyme is sold both fresh and dried. While summer-seasonal, fresh greenhouse thyme is often available year round. The fresh form is more flavourful, but also less convenient; storage life is rarely more than a week. However, the fresh form can last many months if carefully frozen.

Fresh thyme is commonly sold in bunches of sprigs. A sprig is a single stem snipped from the plant. It is composed of a woody stem with paired leaf or flower clusters (“leaves”) spaced 1⁄2 to 1 inch (13 to 25 mm) apart. A recipe may measure thyme by the bunch (or fraction thereof), or by the sprig, or by the tablespoon or teaspoon. Dried thyme is widely used in Armenia in tisanes (called urc).

Depending on how it is used in a dish, the whole sprig may be used (e.g., in a bouquet garni), or the leaves removed and the stems discarded. Usually, when a recipe specifies “bunch” or “sprig”, it means the whole form; when it specifies spoons, it means the leaves. It is perfectly acceptable to substitute dried for whole thyme.

Leaves may be removed from stems either by scraping with the back of a knife, or by pulling through the fingers or tines of a fork.

Thyme retains its flavor on drying better than many other herbs.

Figure 2. Dried thyme

Health benefits of thyme

The therapeutic potential of thyme rests on its contents of thymol, flavonoids, carvacrol, p-cymene, β-pinene, γ-terpinene, β-caryophyllene, 1-borneol, 1,8-cineole, eugenol, aliphatic phenols as well as saponins, and tetramethoxylated flavones ⁷, ⁸, ⁹. Besides possession of antimicrobial action, thyme essential oil functions as phytoprotective agents, defending the plant from herbivores and lethal pathogens ¹⁰. Though the modes of action of the thyme extracts are not known, their antimicrobial agents include thymol, terpenes, eugenol, flavones, glycosides of phenolic monoterpenoids and aliphatic alcohols among other elements ¹¹. These substances acting alone or in combination may result in a broad spectrum of antimicrobial activity exhibited for both bacteria and fungi.

Thymol is a natural compound isolated from thyme. It has antiseptic, antifungal, and strong antibacterial activities ¹². It also has a powerful antioxidant activity ¹³. Previously published data show remarkable differences in the volatile composition of thyme in different countries. Thyme accumulates high amounts of thymol including 42.63 %, (in Pakistan), 64.6 % (in India), and 81.5 % (in Armenia) ¹⁴. Contrary to these countries, thymol and carvacrol were not detected in the thyme from Lithuania, Sweden, Finland and Poland ¹⁴.

Thyme was also found to have a significant antiparasitic effect against bird protozoan, Trichomonas gallinae ¹⁵, and in vitro scolicidal effects against Hydatid cyst ¹⁶. However in a test tube study involving thyme oil extract, it failed to kill Salmonella choleraesuis or Klebsilela pneumoniae but stopped the growth of Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans ¹⁷. In another test tube study, the essential oil of thyme, tested by macrodilution method, showed very strong antifungal activity. A concentration of 0.25 μL/mL of oil inhibited Alternaria alternata, Fusarium tricinctum, all Aspergillus species and dermatomycetes ¹⁸. Phomopsis helianthi and Cladosporium cladosporioides were inhibited at lower concentrations (0.125 μL/mL). Strong antifungal activity of thymol and carvacrol were also reported in the literature ¹⁹. Comparing the previous data with the chemical composition of thyme oils, it becomes evident that there is a relationship between the high activity of the thyme type oils and the presence of phenol components, such as thymol and carvacrol. The high antifungal activity of these essential oils could be explained by the high percentage of phenol components. It seems possible that phenol components may interfere with cell wall enzymes like chitin synthase/chitinase as well as with the α- and β- glucanases of the fungus ²⁰. Consequently, the high content of phenol components may account for the high antifungal activity of thyme essential oils ²¹. However, the reason why yeast is more susceptible to the thyme oil extracts than bacteria is unclear but it may be that at any given time, these oils may break up the structural integrity of Candida albicans faster than they dissociate bacteria ¹⁷.

Taken together, these results suggest that thyme essential oil could find practical application in the prevention and protection of fungal infections of plants, animals and humans. Thyme essential oils could safely be used as preservative materials on foods for protection to fungal infection, since they are natural, and mostly non-toxic to humans. Furthermore, thyme is popular culinary herb and thyme essential oil has been used extensively for many years in food products, perfumery, and dental and oral products.

1. Chemical composition of essential oils of Thymus and Mentha species and their antifungal activities. Soković MD, Vukojević J, Marin PD, Brkić DD, Vajs V, van Griensven LJ. Molecules. 2009 Jan 7; 14(1):238-49. https://www.ncbi.nlm.nih.gov/pubmed/19136911/[↩]
2. Sthal-Biskup E, Saez F. Thyme: the genus Thymus (Medicinal and Aromatic Plants-Industrial Profiles) J Essent Oil Res. 2002;330:415–848.[↩]
3. Antimicrobial activity of spices. Arora DS, Kaur J. Int J Antimicrob Agents. 1999 Aug; 12(3):257-62. https://www.ncbi.nlm.nih.gov/pubmed/10461845/[↩]
4. In-vitro antimicrobial activity and chemical composition of Sardinian Thymus essential oils. Cosentino S, Tuberoso CI, Pisano B, Satta M, Mascia V, Arzedi E, Palmas F. Lett Appl Microbiol. 1999 Aug; 29(2):130-5. https://www.ncbi.nlm.nih.gov/pubmed/10499301/[↩]
5. https://www.listerine.com/active-ingredients[↩]
6. Chemical Composition of Essential Oils of Thymus and Mentha Species and Their Antifungal Activities. Molecules 2009, 14(1), 238-249; doi:10.3390/molecules14010238[↩]
7. Safaei-Ghomi J, Ebrahimabadi AH, Djafari-Bidgoli Z, Batooli H. GC/MS analysis and in vitro antioxidant activity of essential oil and methanol extracts of Thymus caramanicus Jalas and its main constituent carvacrol. Food Chem. 2009;115:1524–1528. doi: 10.1016/j.foodchem.2009.01.051.[↩]
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9. Deans SG, Ritchie GA. Antimicrobial properties of plant essential oils. Int J Food Microbiol. 1987;5:165–180.[↩]
10. Pharmacological and chemical investigation of thyme liquid extracts. Van den Broucke CO, Lemli JA. Planta Med. 1981 Feb; 41(2):129-35.[↩]
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12. Mathela CS. Singh KK. Gupta VK. Synthesis and in vitro antibacterial activity of thymol and carvacrol derivatives. Acta Pol Pharm. 2010;67:375–380.[↩]
13. Ahmad A, Khan A, Yousuf S, Khan LA, Manzoor N. Proton translocating ATPase mediated fungicidal activity of eugenol and thymol. Fitoterapia. 2010;81:1157–1162.[↩]
14. Loziene K, Venskutonis PR. Chemical composition of the essential oil of Thymus serpyllum L. ssp. serpyllum growing wild in Lithuania. J Essent Oil Res. 2006;18:206–211. doi: 10.1080/10412905.2006.9699067.[↩][↩]
15. Nasrabadi NT, Mirghasemi N, Bakhtiari N, Zarrinkoub N, Mirghasemi N. Comparison of anti-parasitic effects of garden thyme (Thymus vulgaris) extract and metronidazole on Trichomonas gallinae. RPS. 2012;7,Suppl.[↩]
16. Moazeni M, Saharkhiz MJ, Hosseini AA. In vitro lethal effect of a jowan (Trachysperm umammi L.) essential oil on hydatid cyst protoscoleces. Vet Parasitol. 2012;187:203–208.[↩]
17. Nzeako BC, Al-Kharousi ZSN, Al-Mahrooqui Z. Antimicrobial Activities of Clove and Thyme Extracts. Sultan Qaboos University Medical Journal. 2006;6(1):33-39. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3074903/[↩][↩]
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21. Adam, K.; Sivropoulou, A.; Kokkini, S.; Lanaras, T.; Arsenakis, M. Antifungal activities of Origanum vulgare subsp. hirtum, Mentha spicata, Lavandula angustifolia and Salvia fruticosa essential oils against human pathogenic fungi. J. Agric. Food Chem. 1998, 46, 1738–1745.[↩]

What are lentils

Lentil (Lens culinaris; Family: Fabaceae) is an annual indigenous plant from Western Asia and other parts of the world, including North America. The lentil is an edible pulse ¹. Lentil is a bushy annual plant of the legume family, known for its lens-shaped seeds, which has the most significant dietary compositions, containing macro- and micro-nutrients ². Lentil is about 40 cm (16 in) tall, and the seeds grow in pods, usually with two seeds in each. Lentils play an important role in crop rotation and the ability to fix atmospheric nitrogen.

Lentils are the world’s oldest cultivated legume, so it’s no surprise that lentils have become a staple across the globe – from India to the Middle East, Europe, and the Americas. Like beans, lentils add a great high-fiber and high-protein element to many meals. Because of their size, lentils cook much more quickly than dried beans and do not have to be soaked before cooking. They are extremely versatile and inexpensive, which makes them an accessible form of high-quality protein.

Lentils exist as a spectrum of colors, which includes yellow, orange, red, green, brown or black, depending on the cultivar, the composition of the seed coats and cotyledons ³. The color of dehulled seeds is mainly associated with the cotyledon color, which could be yellow, red or green. While the color of the intact seed is based on the seed coat, it could be tan, brown, green, gray or black. The seed coats of lentil have a higher amount of flavan-3-ols, proanthocyanidins and some flavonols. This suggests that lentil featuring green and gray seed coats might be more promising for a health-promoting diet. According to the Food and Agriculture Organization statistics report in 2014, the global production of the lentils was primarily cultivated and harvested by Canada and India, which were estimated to be 1.99 million and 1.1 million metric tons, followed by Turkey (0.34 million), Nepal (0.22 million) and China (0.125 million). The evidence demonstrated that the consumption of lentils is highly associated with reductions in the incidence of degenerative diseases including diabetes, cardiovascular disease (CVD) and cancers. There has been an increase in scientific interest of the study of lentils as a functional food due to their high nutritional compositions, nutritive value and the presence of bioactive secondary metabolites. These bioactive compounds in lentils play a vital role in the prevention of degenerative diseases in humans and a significant role in improving health.

Lentil Types

There are four main categories of lentils: brown, green, red/yellow, and specialty.

Brown Lentils

Brown lentils are the most common variety – any bag in the grocery store that says “lentils” without any other descriptor is most likely full of brown lentils. This variety can range in color from khaki brown to dark black and has a mild, earthy flavor.

Good For:

This variety holds its shape well during cooking, making it ideal for use in warm salads, casseroles, soups, and stews. Brown lentils also work well in veggie burgers or vegetarian meatloaf.

To Cook:

In a medium pot, combine 1 cup dry brown lentils with 2½ to 3 cups of water. Bring to a boil and then simmer for 35–45 minutes until tender. If they will be used in a soup or stew, add them to the pot with about 40 minutes cooking time left.

Green Lentils

Green lentils are extremely similar to brown lentils, but they have a more robust and slightly peppery flavor and come in a range of sizes. Green lentils can vary in color from a pale or spotted green to a green-slate color with hints of blue and black. Pro tip: Green lentils are a great (and less expensive) substitute for the famous French Puy lentils.

Good For:

Like brown lentils, green lentils retain their shape well. This, combined with their strong flavor, makes green lentils ideal for salads or side dishes.

To Cook:

Combine 1 cup lentils with 2½ cups water. Bring to a boil and simmer 35–45 minutes until tender. (Don’t forget to flavor the cooking water with some aromatics or herbs for a tastier end product.)

Red and Yellow Lentils

This variety of lentil ranges in color from golden yellow to orange and red. They are also the only variety sold “split,” meaning they processed into smaller lentil bits. These somewhat sweet and nutty lentils are very common in Indian and Middle Eastern cuisine and are the key to classic dishes such as Indian dhal.

Good For:

Because of their “split” nature, this variety of lentil tends to disintegrate when cooked, making them ideal to use in soups or stews (especially as a thickener), and in casseroles or any other dish where they are pureed.

To Cook:

Split lentils cook quickly, usually in about 15–30 minutes.2425 When you’re using them in a soup or stew, just add them to the pot with 15–30 minutes left in the cooking time. When cooking them on their own, bring 1½ cups water and 1 cup dry lentils to a boil, then simmer until tender, 10–15 minutes.

Specialty Lentils

There are many varieties of specialty lentils, but two are most common: Black beluga and Puy. Both varieties are about one-third of the size of brown or green lentils and have a rich, earthy flavor.

Black Beluga Lentils

When cooked, black beluga lentils are shiny, tiny, and black – they look kind of like caviar: hence their name.

Good For:

Thanks to their rich, earthy flavor, soft texture, and beautiful appearance, these lentils make a great base for salads or as a feature with any kind of protein.

To Cook:

Combine 2¼ cups water and 1 cup lentils. Bring to a boil and simmer 25–30 minutes or until tender.

Puy Lentils

Puy lentils are grown in the volcanic soil of a specific region in central France called Le Puy. Puy lentils are known for their dark, bluish-slate-green color and rich, peppery flavor.

Good For:

These high-quality lentils should star as the center of a meal. They make a great base for meat or fish, or can be easily featured in a side dish or main dish salad.

To Cook:

Combine 2½ cups water with 1 cup lentils. Bring to a boil and simmer 20–30 minutes until tender.

Whether in a salad or soup or as the base of a main dish, lentils make a hearty and healthy addition to any meal. If using a recipe isn’t possible, it’s easy to whip up a tasty lentil-based dish without a lot of direction. Follow the guidelines regarding water to lentil ratio, and add plenty of flavorings to the water itself – an onion (quartered), a bay leaf, or a bundle of other herbs – to flavor the lentils as they cook. Serve with a pan of roasted vegetables and a piece of meat for an easy, complete meal. Lentils easily take the place of any hearty grain or legume in most recipes or cooking applications.

Figure 1. Lentils

Lentils Preparation, Cooking, and Storage

Lentils are sold in two forms: canned and dried. While canned are good for ready-to-eat uses such as a quick salad or side dish, the dried version works well for soups and stews, salads, and sides. A bag of dried lentils can really last forever, but they are best used within a year of purchase (or by the date printed on the package). Once the bag is opened, store any remaining lentils in an airtight container and keep them in a cool, dry place.

One benefit of lentils is that they can be cooked in less than an hour. While it seems like an unnecessary step, don’t skip rinsing your lentils and sifting through them before cooking to remove any stones or debris. It is rare to find stones, but it does happen. When cooking, treat lentils more like pasta than rice – the lentils do not need to absorb every bit of cooking liquid the way rice does, but you also don’t need to completely flood the lentils like you would pasta. As a general rule, one cup of dried lentils yields two to two-and-a-half cups of cooked lentils.

Because of their rather delicate, earthy flavor, lentils work well in a variety of dishes and in almost any type of cuisine. The best time to add flavor to lentils is during the cooking process. Don’t be afraid to get creative. Adding half an onion (peeled), a few cloves of crushed garlic, a bundle of herbs, or a bay leaf to the cooking liquid and a pinch of salt gives lentils plenty of flavor, especially when they’re the base for a salad or side dish.

Lentils nutrition facts

Nutritional compositions of raw, sprouted and cooked lentils are summarized in Table 1. According to the USDA National Nutrient Database, 100 g of raw lentils (variety unspecified) provide 352 calories; the same weight of cooked lentils provides 116 calories. Raw lentils are 8% water, 63% carbohydrates including 11% dietary fiber, 25% protein, and 1% fat (see Table 1). Lentils are a rich source (20% or more of the Daily Value, DV) of numerous essential nutrients, including folate (120% DV), thiamin (76% DV), pantothenic acid (43% DV), vitamin B6 (42% DV), phosphorus (40% DV), iron (50% DV), and zinc (35%), among others. When lentils are cooked by boiling, protein content declines to 9% of total composition, and B vitamins and minerals decrease due to the overall water content increasing (protein itself is not lost) ⁴.

Lentils are known to have the second-highest ratio of protein per calorie of any legume, after soybeans, providing essential and non-essential amino acids to the human body. The predominant proteins in lentils are globulin (47% of the total seed proteins) and an adequate quantity of albumin ⁵. High quantities of these proteins and essential amino acids in lentils offer an important dietary source for low and middle-income countries ⁶.

Among 23 pulses, lentils yield the second highest starch percentage of 47.1% and a greater percentage of insoluble dietary fibers ⁷. The low levels of readily digestible starch (5%) and high levels of slowly digested starch make lentils of potential value to people with diabetes ⁸. The remaining 65% of the starch is a resistant starch classified as RS1. Lentils have nutritionally important quantities of prebiotic carbohydrates (12.3–14.1 g/100 g of dry lentils), also known as “resistant starch” that  escapes digestion and absorption in the small intestine ⁹, making lentils a good source of prebiotics ¹⁰ that help to keep up the gut microbial environment and prevent gut-associated diseases ¹¹.

Furthermore, lentils are relatively low in fat and sodium, but high in potassium content (1:30 ratio of sodium and potassium) ¹². Given that, it is the best dietary food for patients with obesity and cardiovascular disease. Lentil seeds are an excellent vegetable source of iron. Studies have shown that the consumption of cooked lentil in the diet prevents iron deficiency anemia ¹³, iron being a very important mineral, which is required daily, especially for adolescents and pregnant women. Several minerals (zinc, copper, manganese, molybdenum, selenium and boron) and vitamins (thiamine, riboflavin, niacin, pantothenic acid, pyridoxine, folate, α, β and γ tocopherols and phylloquinone) have been well documented in lentils ¹⁴. Moreover, lentils have an average quantity of vitamin K of 5 μg/100 g, as reported by the United States Department of Agriculture (USDA) ¹⁵. However, the daily requirement of this vitamin in adults is about 80 μg. The low content of vitamin K renders lentils as safe for patients with cardiovascular disease upon anticoagulant treatment. Overall, lentils are considered as one of the best dietary sources that has health-promoting effects on various illnesses.

On the down side, lentils also have antinutrient factors, such as trypsin inhibitors and a relatively high phytate content. Trypsin is an enzyme involved in digestion, and phytates reduce the bioavailability of dietary minerals ¹⁶. The phytates can be reduced by prolonged soaking and fermentation or sprouting.

Table 1. Lentils (raw) nutrition facts

Bioactive Compounds in Lentils

Various bioactive compounds or secondary metabolites are present in the lentil seed, which are categorized into different functional groups. The bioactive functional groups and their quantity in lentils are listed in Table 2.

Table 2. List of bioactive functional groups in lentils and their biological functions

Polyphenols in Lentils

Lentils have the highest total phenolic content in comparison to six other common legumes, such as green pea, chickpea, cowpea, yellow pea, mung bean and peanut ²⁵. Polyphenols are generally a large group of compounds, classified into different classes, based on the presence of the number of phenolic rings and their structural elements or substituents ³⁰. Two main groups can be identified based on the aromatic rings, which are attached to the heterocyclic rings, known as the flavonoid groups (flavones, flavonols, flavanones, flavanonols, flavanols or catechins, anthocyanins, neoflavonoids and chalcones) and the non-flavonoid groups (simple phenols, phenolic acids, hydroxybenzoic acids, tannins, acetophenones and phenylacetic acids; hydroxycinnamic acids, coumarins, benzophenones, xanthones, stilbenes, lignans and secoiridoids) ³⁰, ³¹. Various functional polyphenols in the lentils are described according to their classes and subclasses in Table 3.

Table 3. List of polyphenols in lentils

Health benefits of lentils

Polyphenol-rich lentils have potential health benefits as complementary and alternative medicines, which are exerted in the form of antioxidant, antibacterial, anti-fungal, antiviral, cardioprotective, anti-inflammatory, nephroprotective, antidiabetic, anticancer, anti-obesity, hypolipidemic and chemopreventive activities. Furthermore, lentils are useful as a prognostic marker for various cancers including thyroid and hepatic carcinoma.

Anti-Diabetic Activity of Lentils

Świeca et al. ³³ observed that the regular consumption of the germinated lentils is beneficial for the prevention and management of diabetes. Lentils have the ability to improve blood glucose, lipid and lipoprotein metabolism in diabetic and healthy human beings ³⁴. Human diabetes studies of polyphenol-rich lentil seed showed the anti-diabetic potentials of lentils. The regular consumption of cooked lentils (50 g) among diabetic patients leads to significant reductions of fasting blood sugar and glycemic load ³⁵. Reductions of the glycemic index from the diet are due to the presence of polyphenols in the lentils that have been linked with health-promoting impacts on metabolic disorders such as diabetes, obesity, coronary heart diseases and cardiovascular disease ³⁶. Furthermore, in vitro and in vivo studies have also demonstrated that lentils in the diet regulate starch digestibility, glycemic load and the glycemic index, which diminish diabetes complications ³⁷. ³⁸. In a study involving forty- eight overweight and obese type 2 diabetic patients who ate 60 grams of lentil sprouts daily for 8 weeks in addition to the usual medications, diets and exercise pattern ³⁹. Although the weight did not differ significantly between 2 groups (ie. lentil sprouts group and control group who ate normal diet) after 8 weeks intervention. In that short study, the lentil sprouts subjects improved their glycemic control and reduce their serum lipids and increase their HDL “good” cholesterol level after 8 weeks of lentil sprouts consumption and this effect could be due to some bioactive components in lentil sprouts ⁴⁰. Thus, a diet including lentils appears to be an effective intervention and management strategy for the prevention of diabetes. A large, well-designed randomized controlled trial is needed to assess the potential value of lentils in improving diabetes.

Antioxidant Potential of Lentils

A wide range of in vitro evidence implies that lentils have the highest total antioxidant capacity when they are compared to chickpeas, common beans and soybeans, which were measured by 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power, oxygen radical absorbing capacity, Trolox equivalent antioxidant capacity and total radical-trapping antioxidant parameters [51,52,53,54]. Evidence has shown that lentils have greater oxygen radical scavenging potential compared to various vegetables and fruits, such as onion, horseradish, potatoes, wheat germ, blueberries and sweet cherries. Lentils have different groups of phenolic compounds such as procyanidin and prodelphinidin dimers and trimers, gallate procyanidins, kaempferol derivatives, quercetin glucoside acetate, luteolin derivatives and p-coumaric acid, hydroxybenzoic compounds, protocatechuic, vanillic acid, aldehyde p-hydroxybenzoic, trans-ferulic acid and trans-p-coumaric acid, compared to other legumes, providing greater antioxidant potentials and health-promoting effects. These phenolic compounds in lentils naturally act as antioxidants and have the ability to restrict the formation of reactive oxygen species, as well as superoxide anion by chelating metal ions or inhibiting enzymes ⁴¹. Further research is needed to confirm these findings.

Anti-Obesity Activity of Lentils

Large prospective epidemiological studies have reported that the intake of phenolic-rich lentils is inversely connected with the incidence of obesity and diabetes ⁴². An earlier human study shows that the intake of lentil seed along with pasta and sauce reduces food intake, body weight and waist circumference ⁴³. Furthermore, lentil seed containing flavonoids and fiber enhances satiety and lowers the amount of food intake, which lead to maintaining body weight in obese subjects ⁴³. Observational studies have further reported an inverse relationship between the consumption of lentils and the basal metabolic index or risk associated with obesity ⁴⁴. Besides that, interventional studies have shown the potential of lentils to inhibit α-glucosidase and pancreatic lipase, which has the ability to decrease glucose and fat digestion and absorption in the intestine. Ultimately, polyphenol-rich lentils control postprandial glucose and fat, which is crucial in the management of diabetes and obesity ⁴⁵. Flavonoids in lentils have the potential to inhibit the actions of α-glucosidase and lipase, which suggests that dietary lentil consumption could manage post-prandial blood glucose and body weight ⁴⁶. Further research is needed to evaluate the usefulness of lentils in managing obesity.

Cardioprotective Effect of Lentils

Phenolic-rich lentil seed consumption has been inversely linked with the occurrence of various cardiovascular diseases ⁴⁷. Lentils containing polyphenols have the potential to reduce blood pressure by angiotensin I-converting enzyme (ACE) inhibitor activity ⁴⁸. The recent study observed that bioactive compounds (legumin, vicilin and convicilin) in lentil possess higher antioxidant, ACE-inhibitory and cardioprotective activity ⁴⁹. Besides that, the polyphenol-rich lentil seeds have the ability of antihyperlipidemic, hypohomocysteinemic, anti-cholesterolemic and a cardioprotective effect that reduces the risk of hypertension and coronary artery diseases ⁵⁰. In the hypertensive animal model, administration of lentils actively reduces the total cholesterol (TC), triglycerides (TG), low density lipoprotein (LDL) and pathological manifestations of cardio-morphometric analysis. These findings reinforce the importance of lentil seed and its diet prescription as a therapeutic potential for hypertensive patients ⁵¹. Al-Tibi et al. ⁵² observed that treatment with lentil seeds reduces the glycemic index and hyperlipidemic effects in the STZ-induced diabetic animal model. In this study, lentils significantly raised the high density lipoprotein (HDL) levels and reduced blood glucose levels in diabetic rats. Concisely, these studies recommend that the dietary consumption of polyphenol-rich lentils should be on a regular basis, having the potential to decrease the risk of cardiovascular and coronary artery diseases by lowering serum total and LDL cholesterol ⁵³.

Antimicrobial Activity of Lentils

Lentils containing flavonoids and lectins have been reported as non-toxic and safe for use in medical diagnostic kits ⁵⁴. A bioactive peptide called “defensing”, which is isolated from germinated lentil seeds, possesses a broad spectrum of biological activities, including antimicrobial activities against various infections associated with bacteria and fungi ⁵⁵. It is a group of “host defense peptides” synthesized in the lentil seeds, which are involved in the development of innate immunity. They are tiny, basic, cysteine-rich peptides, containing antifungal activity, which inhibit the growth of Aspergillus niger ⁵⁶. Likely, “defensins” can interrupt viral digestive enzymes, such as human immunovirus (HIV)-1 reverse transcriptase, which impacts viral replication. “Defensins” have been further observed to block ion channels and to inhibit protein translation. Therefore, “defensing” in lentil seeds along with phenolic compounds acts as a potential inhibitor of microbial growth. Additional studies are needed before a more definitive link between lentils and its alleged antimicrobial activity can be established.

Anticancer Activity of Lentils

The consumption of lentil seeds reduces the incidence of various cancers including colon, thyroid, liver, breast and prostate ⁵⁷. A large prospective epidemiologic study associated with polyphenol-rich lentils and breast cancer on 90,630 women exhibited an inverse relationship between lentils and the risk of breast cancer ⁵⁸. Lentil seeds have a high polyphenolic content that potentially could prevent carcinogens through chemo-preventive activities, including the uptake of carcinogens, activation or formation, detoxification, binding to DNA and fidelity of DNA repair ⁵⁹. Moreover, lectins in lentils have anticancer properties, which have been observed in various in vitro, in vivo and human studies ⁶⁰. These lectins along with phenolic compounds in lentil seeds have been proven as therapeutic agents. They potentially bind to cancer cell membranes/receptors, causing cytotoxicity, apoptosis and autophagy; thereby, they inhibit the growth of tumors ⁶⁰. The underlying mechanism of the anticancer potential of lectins and phenolic compounds in lentil is that they bind to ribosomes, which inhibits protein synthesis. Furthermore, this provokes a change of the cell cycle by inducing non-apoptotic G1-phase accumulation mechanisms, G2/M phase cell cycle arrest and apoptosis. In addition to that, this can also activate the caspase cascade in mitochondria and downregulate telomerase activity, which inhibits angiogenesis ⁶¹. Thus, lectins and phenolic compounds derived from lentil seeds seem to be promising therapeutic agents against tumorigenesis or cancer cell agglutination and/or aggregation. The lentil seeds and their chemo-preventive potential on colorectal carcinogenesis have been well documented using azoxymethane, significantly reducing the number of dysplastic lesions and neoplasms in the colon of rats ⁶². In addition, lentils have greater chemopreventive potential when compared to green and yellow peas ⁶³. This is because lentils contain antioxidant bioactive compounds such as flavonoids (flavanones, flavan-3-ols, flavones, flavonols, anthocyanidins and tannins, including condensed tannins or proanthocyanidins) that are greatly responsible for chemoprevention. This chemo-preventive potential is not constrained to polyphenolic-rich lentils or split seeds. More studies are needed in order to establish a definitive link between anti-cancer activity, cancer reduction and lentils consumption.

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What is camomile

Camomile or Chamomile (American English) is the common name for several daisy-like plants of the family Asteraceae or Compositae family and represented by two common varieties viz. German camomile (Chamomilla recutita) and Roman camomile (Chamaemelum nobile) ¹. Extracts, oils and teas made from camomile are used for its soothing qualities as a sedative, mild analgesic and sleep medication. The dried flowers of camomile contain many terpenoids and flavonoids contributing to its medicinal properties ². Camomile preparations are commonly used for many human ailments such as hay fever, inflammation, muscle spasms, menstrual disorders, insomnia, ulcers, wounds, gastrointestinal disorders, rheumatic pain, and hemorrhoids ², ³. Essential oils of camomile are used extensively in cosmetics and aromatherapy. Many different preparations of camomile have been developed, the most popular of which is in the form of herbal tea consumed more than one million cups per day.

Camomile flower

The hollow, bright gold cones of the camomile flowers are packed with disc or tubular florets and are ringed with about fifteen white ray or ligulate florets (see Figure 1 and 2). The flowering tops of the camomile plant are used to make teas, liquid extracts, capsules, or tablets. The herb can also be applied to the skin as a cream or an ointment, or used as a mouth rinse.

Figure 1. German camomile flower (Chamomilla recutita)

Figure 2. Roman camomile flower (Chamaemelum nobile)

Bioactive Compounds of Camomile

Different classes of bioactive constituents are present in camomile, which have been isolated and used as medicinal preparations and cosmetics ⁴. The plant contains 0.24%–1.9% volatile oil, composed of a variety of separate oils. When exposed to steam distillation, the oil ranges in color from brilliant blue to deep green when fresh but turns to dark yellow after storage. Despite fading, the oil does not lose its potency. Approximately 120 secondary metabolites have been identified in chamomile, including 28 terpenoids and 36 flavonoids ⁵. The principal components of the essential oil extracted from the German camomile flowers are the terpenoids α-bisabolol and its oxide azulenes including chamazulene and acetylene derivatives. Chamazulene and bisabolol are very unstable and are best preserved in an alcoholic tincture. The essential oil of Roman camomile contains less chamazulene and is mainly constituted from esters of angelic acid and tiglic acid. It also contains farnesene and α-pinene. Roman chamomile contains up to 0.6% of sesquiterpene lactones of the germacranolide type, mainly nobilin and 3-epinobilin. Both α-bisabolol, bisabolol oxides A and B and chamazulene or azulenesse, farnesene and spiro-ether quiterpene lactones, glycosides, hydroxycoumarins, flavanoids (apigenin, luteolin, patuletin, and quercetin), coumarins (herniarin and umbelliferone), terpenoids, and mucilage are considered to be the major bio-active ingredients ⁶. Other major constituents of the flowers include several phenolic compounds, primarily the flavonoids apigenin, quercetin, patuletin as glucosides and various acetylated derivatives. Among flavonoids, apigenin is the most promising compound. It is present in very small quantities as free apigenin, but predominantly exists in the form of various glycosides ⁷.

Traditional Uses of Camomile

Traditionally, camomile has been used for centuries as an anti-inflammatory, antioxidant, mild astringent and healing medicine ⁸. As a traditional medicine, it is used to treat wounds, ulcers, eczema, gout, skin irritations, bruises, burns, canker sores, neuralgia, sciatica, rheumatic pain, hemorrhoids, mastitis and other ailments ⁹. Externally, camomile has been used to treat diaper rash, cracked nipples, chicken pox, ear and eye infections, disorders of the eyes including blocked tear ducts, conjunctivitis, nasal inflammation and poison ivy ¹⁰. Camomile is widely used to treat inflammations of the skin and mucous membranes, and for various bacterial infections of the skin, oral cavity and gums, and respiratory tract. Camomile in the form of an aqueous extract has been frequently used as a mild sedative to calm nerves and reduce anxiety, to treat hysteria, nightmares, insomnia and other sleep problems ¹¹. Camomile has been valued as a digestive relaxant and has been used to treat various gastrointestinal disturbances including flatulence, indigestion, diarrhea, anorexia, motion sickness, nausea, and vomiting ¹². Camomile has also been used to treat colic, croup, and fevers in children ¹³. It has been used as an emmenagogue (a substance that stimulates or increases menstrual flow) and a uterine tonic in women. It is also effective in arthritis, back pain, bedsores and stomach cramps.

Camomile benefits

What is camomile good for ?

The camomile most commonly used for its hypnotic and sedative effects is German chamomile (Matricaria recutita). Camomile extracts contain volatile oils, flavonoids and hydroxycoumarins. The flavonoid apeginin has benzodiazepine-like activity and is believed to be the active component of camomile.

Camomile has multiple biologic effects in vitro and in vivo, including antiinflammatory, antioxidant, analgesic and sedative effects. In humans, chamomile has been claimed to induce relaxation and sedation and has been used to treat nervousness and insomnia. It is also used for cough, bronchitis, fever, wounds, mouth ulcers, burns, circulatory disorders, dyspepsia, depression and hair loss. Chamomile oils are commonly used in aromatherapy and are found in many skin lotions, creams, soaps and cosmetics. Chamomile is most often used as an herbal tea, but can also be inhaled, applied topically, or taken orally as tablets or capsules usually in combination with other herbals such as passionflower, aloe or valerian or with mild analgesics or antihistamines. Chamomile has not been approved for use in any medical condition in the United States, but it is found in several hundred over-the-counter preparations. Side effects are uncommon may include nausea, dizziness and allergic reactions.

Sleep aid/sedation

Traditionally, camomile preparations such as camomile tea and essential oil aromatherapy have been used to treat insomnia and to induce sedation (calming effects). Camomile is widely regarded as a mild tranquillizer and sleep-inducer. Sedative effects may be due to the flavonoid, apigenin that binds to benzodiazepine receptors in the brain ¹⁴. Studies in preclinical models have shown anticonvulsant and central nervous system (CNS) depressant effects respectively. Clinical trials are notable for their absence, although ten cardiac patients are reported to have immediately fallen into a deep sleep lasting for 90 minutes after drinking chamomile tea ¹⁵. Chamomile extracts exhibit benzodiazepine-like hypnotic activity ¹⁶. In another study, inhalation of the vapor of camomile oil reduced a stress-induced increase in plasma adrenocorticotropic hormone (ACTH) levels. Diazepam, co-administered with the chamomile oil vapor, further reduced ACTH levels, while flumazenile, a benzodiazepine antagonist blocked the effect of camomile oil vapor on ACTH. According to Paladini et al. ¹⁷, the separation index (ratio between the maximal anxiolytic dose and the minimal sedative dose) for diazepam is 3 while for apigenin it is 10. Compounds, other than apigenin, present in extracts of chamomile can also bind benzodiazepine and gamma-aminobutyric acid (GABA) receptors in the brain and might be responsible for some sedative effect; however, many of these compounds are as yet unidentified.

Anxiety and seizure

Chamomile has been reported in the treatment of generalized anxiety disorder. But the reports seem contradictory as an earlier report suggests that German chamomile showed significant inhibition of generalized anxiety disorder activity ¹⁸. The recent results from the controlled clinical trial on chamomile extract for generalized anxiety disorder suggests that it may have modest anxiolytic activity in patients with mild to moderate generalized anxiety disorder ¹⁹. Extracts of chamomile (M. recutita) possess suitable effects on seizure induced by picrotoxin ²⁰. Furthermore, apigenin has been shown to reduce the latency in the onset of picrotoxin-induced convulsions and reduction in locomotor activity but did not demonstrate any anxiolytic, myorelaxant, or anticonvulsant activities ²¹.

Anti-inflammatory and antiphlogistic properties of Camomile

The flowers of camomile contain 1–2% volatile oils including alpha-bisabolol, alpha-bisabolol oxides A and B, and matricin (usually converted to chamazulene and other flavonoids which possess anti-inflammatory and antiphlogistic properties ¹³. A study in human volunteers demonstrated that chamomile flavonoids and essential oils penetrate below the skin surface into the deeper skin layers ²². This is important for their use as topical anti-inflammatory agents. One of camomile’s anti-inflammatory activities involve the inhibition of LPS-induced prostaglandin E(2) release and attenuation of cyclooxygenase (COX-2) enzyme activity without affecting the constitutive form, COX-1 ²³.

Anticancer activity

Most evaluations of tumor growth inhibition by chamomile involve studies with apigenin which is one of the bioactive constituents of chamomile. Studies on preclinical models of skin, prostate, breast and ovarian cancer have shown promising growth inhibitory effects ²⁴. In a recently conducted study, camomile extracts were shown to cause minimal growth inhibitory effects on normal cells, but showed significant reductions in cell viability in various human cancer cell lines. Camomile exposure induced apoptosis in cancer cells but not in normal cells at similar doses ²⁵. The efficacy of the novel agent TBS-101, a mixture of seven standardized botanical extracts including chamomile has been recently tested. The results confirm it to have a good safety profile with significant anticancer activities against androgen-refractory human prostrate cancer PC-3 cells, both in vitro and in vivo situation ²⁶.

Common cold

Common cold (acute viral nasopharyngitis) is the most common human disease. It is a mild viral infectious disease of the upper respiratory system. Typically common cold is not life-threatening, although its complications (such as pneumonia) can lead to death, if not properly treated. Studies indicate that inhaling steam with chamomile extract has been helpful in common cold symptoms ²⁷; however, further research is needed to confirm these findings.

Cardiovascular conditions

It has been suggested that regular use of flavonoids consumed in food may reduce the risk of death from coronary heart disease in elderly men ²⁸. A study assessed the flavonoid intake of 805 men aged 65–84 years who were followed up for 5 years. Flavonoid intake (analyzed in tertiles) was significantly inversely associated with mortality from coronary heart disease and showed an inverse relation with incidence of myocardial infarction. In another study ¹⁵, on twelve patients with cardiac disease who underwent cardiac catheterization, hemodynamic measurements obtained prior to and 30 minutes after the oral ingestion of chamomile tea exhibited a small but significant increase in the mean brachial artery pressure. No other significant hemodynamic changes were observed after chamomile consumption. Ten of the twelve patients fell into a deep sleep shortly after drinking the beverage. A large, well-designed randomized controlled trial is needed to assess the potential value of chamomile in improving cardiac health.

Colic/Diarrhea conditions

An apple pectin-camomile extract may help shorten the course of diarrhea in children as well as relieve symptoms associated with the condition. Two clinical trials have evaluated the efficacy of chamomile for the treatment of colic in children. Camomile tea was combined with other herbs (German camomile, vervain, licorice, fennel, balm mint) for administration. In a prospective, randomized, double-blind, placebo-controlled study, 68 healthy term infants who had colic (2 to 8 weeks old) received either herbal tea or placebo (glucose, flavoring). Each infant was offered treatment with every bout of colic, up to 150 mL/dose, no more than three times a day. After 7 days of treatment, parents reported that the tea eliminated the colic in 57% of the infants, whereas placebo was helpful in only 26%. No adverse effects with regard to the number of nighttime awakenings were noted in either group ²⁹. Another study examined the effects of a chamomile extract and apple pectin preparation in 79 children (age 0.5–5.5 years) with acute, non-complicated diarrhea who received either the camomile/pectin preparation (n = 39) or a placebo (n = 40) for 3 days. Diarrhea ended sooner in children treated with chamomile and pectin (85%), than in the placebo group (58%) ³⁰. These results provide evidence that chamomile can be used safely to treat infant colic disorders.

Eczema

Topical applications of camomile have been shown to be moderately effective in the treatment of atopic eczema ³¹. It was found to be about 60% as effective as 0.25% hydrocortisone cream ³². Roman chamomile of the Manzana type [Kamillosan (R)] may ease discomfort associated with eczema when applied as a cream containing chamomile extract. The Manzana type of chamomile is rich in active ingredients and does not exhibit chamomile-related allergenic potential. In a partially double-blind, randomized study carried out as a half-side comparison, Kamillosan(R) cream was compared with 0.5% hydrocortisone cream and a placebo consisting only of vehicle cream in patients suffering from medium-degree atopic eczema ³³. After 2 weeks of treatment, Kamillosan(R) cream showed a slight superiority over 0.5% hydrocortisone and a marginal difference as compared to placebo. Further research is needed to evaluate the usefulness of topical chamomile in managing eczema.

Gastrointestinal conditions

Chamomile is used traditionally for numerous gastrointestinal conditions, including digestive disorders, “spasm” or colic, upset stomach, flatulence (gas), ulcers, and gastrointestinal irritation ³⁴. Chamomile is especially helpful in dispelling gas, soothing the stomach, and relaxing the muscles that move food through the intestines. The protective effect of a commercial preparation (STW5, Iberogast), containing the extracts of bitter candy tuft, lemon balm leaf, camomile flower, caraway fruit, peppermint leaf, liquorice root, Angelica root, milk thistle fruit and greater celandine herb, against the development of gastric ulcers has been previously reported ³⁵. STW5 extracts produced a dose dependent anti-ulcerogenic effect associated with a reduced acid output, an increased mucin secretion, an increase in prostaglandin E (2) release and a decrease in leukotrienes. The results obtained demonstrated that STW5 not only lowered gastric acidity as effectively as a commercial antacid, but was more effective in inhibiting secondary hyperacidity ³⁵.

Hemorrhoids

Studies suggest that camomile ointment may improve hemorrhoids. Tinctures of chamomile can also be used in a sitz bath format. Tincture of Roman chamomile may reduce inflammation associated with hemorrhoids ³⁶.

Health Promotion

It has been claimed that consumption of chamomile tea boosts the immune system and helps fight infections associated with colds. The health promoting benefits of chamomile was assessed in a study which involved fourteen volunteers who each drank five cups of the herbal tea daily for two consecutive weeks. Daily urine samples were taken and tested throughout the study, both before and after drinking chamomile tea. Drinking chamomile was associated with a significant increase in urinary levels of hippurate and glycine, which have been associated with increased antibacterial activity ³⁷. In another study, chamomile relieved hypertensive symptoms and decreased the systolic blood pressure significantly, increasing urinary output ³⁸. Additional studies are needed before a more definitive link between chamomile and its alleged health benefits can be established.

Inflammatory conditions

Inflammation is associated with many gastrointestinal disorders complaints, such as esophageal reflux, diverticular disease, and inflammatory disease ³⁹. Studies in preclinical models suggest that chamomile inhibits Helicobacter pylori, the bacteria that can contribute to stomach ulcers ⁴⁰. Chamomile is believed to be helpful in reducing smooth muscle spasms associated with various gastrointestinal inflammatory disorders. Chamomile is often used to treat mild skin irritations, including sunburn, rashes, sores and even eye inflammations ⁴¹ but its value in treating these conditions has not been shown with evidence-based research.

Mucositis

Mouth ulcers are a common condition with a variety of etiologies ⁴². Stomatitis is a major dose-limiting toxicity from bolus 5-fluorouracil-based (5-FU) chemotherapy regimens. A double-blind, placebo-controlled clinical trial including 164 patients was conducted ⁴³. Patients were entered into the study at the time of their first cycle of 5-FU-based chemotherapy and were randomized to receive a chamomile or placebo mouthwash thrice daily for 14 days. There was no suggestion of any stomatitis difference between patients randomized to either protocol arm. There was also no suggestion of toxicity. Similar results were obtained with another prospective trial on chamomile in this situation. Data obtained from these clinical trials did not support the pre study hypothesis that chamomile could decrease 5-FU-induced stomatitis. The results remain unclear if camomile is helpful in this situation.

Osteoporosis

Osteoporosis is a metabolic bone disease resulting from low bone mass (osteopenia) due to excessive bone resorption. Sufferers are prone to bone fractures from relatively minor trauma. Agents which include selective estrogen receptor modulators or SERMs, biphosphonates, calcitonin are frequently used to prevent bone loss. To prevent bone loss that occurs with increasing age, chamomile extract was evaluated for its ability to stimulate the differentiation and mineralization of osteoblastic cells. Chamomile extract was shown to stimulate osteoblastic cell differentiation and to exhibit an anti-estrogenic effect, suggesting an estrogen receptor-related mechanism ⁴⁴. However, further studies are needed before it can be considered for clinical use.

Diabetes

Studies suggest that chamomile ameliorates hyperglycemia and diabetic complications by suppressing blood sugar levels, increasing liver glycogen storage and inhibition of sorbitol in the human erythrocytes ⁴⁵. The pharmacological activity of chamomile extract has shown to be independent of insulin secretion ⁴⁶, and studies further reveal its protective effect on pancreatic beta cells in diminishing hyperglycemia-related oxidative stress ⁴⁷. Additional studies are required to evaluate the usefulness of chamomile in managing diabetes.

Sore throat/hoarseness

The efficacy of lubrication of the endo-tracheal tube cuff with chamomile before intubation on postoperative sore throat and hoarseness was determined in a randomized double-blind study. 161 patients whose American Society of Anesthesiologists  physical status was I or II, and undergoing elective surgical, orthopedic, gynecological or urological surgeries were divided in two groups. The study group received 10 puffs of camomile extract (Kamillosan M spray, total 370 mg of Camomile extract) at the site of the cuff of the endotracheal tube for lubrication, while the control group did not receive any lubrication before intubations. Standard general anesthesia with tracheal intubations was given in both groups. 41 out of 81 patients (50.6%) in the chamomile group reported no postoperative sore throat in the post-anesthesia care unit compared with 45 out of 80 patients (56.3%) in the control group. Postoperative sore throat and hoarseness both in the post-anesthesia care unit and at 24 h post-operation were not statistically different. Lubrication of endo-tracheal tube cuff with chamomile extract spray before intubations can not prevent post operative sore throat and hoarseness ⁴⁸. Similar results were obtained in another double blind study ⁴⁹.

Vaginitis

Vaginal inflammation is common in women of all ages. Vaginitis is associated with itching, vaginal discharge, or pain with urination. Atrophic vaginitis most commonly occurs in menopausal and postmenopausal women, and its occurrence is often associated with reduced levels of estrogen. Camomile douche may improve symptoms of vaginitis with few side effects ⁵⁰. There is insufficient research data to allow conclusions concerning possible potential benefits of camomile for this condition.

Wound healing

The efficacy of topical use of chamomile to enhance wound healing was evaluated in a double-blind trial on 14 patients who underwent dermabrasion of tattoos. The effects on drying and epithelialization were observed, and chamomile was judged to be statistically efficacious in producing wound drying and in speeding epithelialization ⁵¹. Antimicrobial activity of the extract against various microorganisms was also assessed. The test group, on day 15, exhibited a greater reduction in the wound area when compared with the controls (61 % versus 48%), faster epithelialization and a significantly higher wound-breaking strength. In addition, wet and dry granulation tissue weight and hydroxyproline content were significantly higher. The increased rate of wound contraction, together with the increased wound-breaking strength, hydroxyproline content and histological observations, support the use of M. recutita in wound management ⁵². Recent studies suggest that chamomile caused complete wound healing faster than corticosteroids ⁵³. However, further studies are needed before it can be considered for clinical use.

Quality-of-life in cancer patients

Essential oils obtained from Roman chamomile are the basic ingredients of aromatherapy. Clinical trials of aromatherapy in cancer patients have shown no statistically significant differences between treated and untreated patients ⁵⁴. Another pilot study investigated the effects of aromatherapy massage on the anxiety and self-esteem experience in Korean elderly women. A quasi-experimental, control group, pretest-posttest design used 36 elderly females: 16 in the experimental group and 20 in the control group. Aromatherapy massage using lavender, chamomile, rosemary, and lemon was given to the experimental group only. Each massage session lasted 20 min, and was performed 3 times per week for two 3-week periods with an intervening 1-week break. The intervention produced significant differences in the anxiety and self-esteem. These results suggest that aromatherapy massage exerts positive effects on anxiety and self-esteem ⁵⁵. However, more objective, clinical measures should be applied in a future study with a randomized placebo-controlled design.

Contraindications and Safety Issues with Camomile

A relatively low percentage of people are sensitive to camomile and develop allergic reactions ⁵⁶. People sensitive to ragweed and chrysanthemums or other members of the Compositae family are more prone to develop contact allergies to camomile, especially if they take other drugs that help to trigger the sensitization.

• There have been reports of allergic reactions, including rare cases of anaphylaxis (a life-threatening allergic reaction), in people who have consumed or come into contact with chamomile products.
• People are more likely to experience allergic reactions to chamomile if they’re allergic to related plants such as ragweed, chrysanthemums, marigolds, or daisies.
• Interactions between chamomile and cyclosporine (a drug used to prevent rejection of organ transplants) and warfarin (a blood thinner) have been reported, and there are theoretical reasons to suspect that chamomile might interact with other drugs as well. Talk to your health care provider before taking chamomile if you’re taking any type of medicine.

A large-scale clinical trial was conducted in Hamburg, Germany, between 1985 and 1991 to study the development of contact dermatitis secondary to exposure to a mixture of components derived from the Compositae family. Twelve species of the Compositae family, including German chamomile, were selected and tested individually when the mixture induced allergic reactions. During the study, 3,851 individuals were tested using a patch with the plant extract ⁵⁷. Of these patients, 118 (3.1%) experienced an allergic reaction. Further tests revealed that feverfew elicited the most allergic reactions (70.1% of patients) followed by chrysanthemums (63.6%) and tansy (60.8%). Camomile fell in the middle range (56.5%). A study involving 686 subjects exposed either to a sesquiterpene lactone mixture or a mixture of Compositae extracts led to allergic reactions in 4.5% of subjects ⁵⁸. In another study it was shown that eye washing with chamomile tea in hay fever patients who have conjunctivitis exacerbates the eye inflammation, whereas no worsening of eye inflammation was noted when camomile tea was ingested orally ⁵⁹. It is possible that some reports of allergic reactions to camomile may be due to contamination of chamomile by “dog chamomile,” a highly allergenic and bad-tasting plant of similar appearance. Evidence of cross-reactivity of camomile with other drugs is not well documented, and further study of this issue is needed prior to reaching conclusions. Safety in young children, pregnant or nursing women, or those with liver or kidney disease has not been established, although there have not been any credible reports of toxicity caused by this common beverage tea. Chamomile has not been implicated in causing serum enzyme elevations or clinically apparent liver injury ⁶⁰.

Pregnancy and breast-feeding: Roman chamomile is LIKELY UNSAFE when taken by mouth in medicinal amounts during pregnancy. Roman chamomile is believed to cause miscarriages. Not enough is known about the safety of applying it to the skin during pregnancy. Avoid using Roman chamomile if you are pregnant.

It’s also best to avoid Roman chamomile if you are breast-feeding. Not enough is known about how it might affect the nursing infant.

Summary

Camomile has been used as an herbal medication since ancient times, is still popular today and probably will continue to be used in the future because it contains various bioactive phytochemicals that could provide therapeutic effects.

• Some preliminary studies suggest that a chamomile dietary supplement might be helpful for generalized anxiety disorder.
• Some research has found that products containing certain combinations of herbs that include chamomile may be of benefit for upset stomach, for diarrhea in children, and for infants with colic. But chamomile alone has not been shown to be helpful for these conditions.

Establishing whether or not therapeutic effects of camomile are beneficial to patients will require good clinical research and generation of scientific evidence. There is a need for continued efforts that focuses on various diseases, which are then consequently validated in clinical trials that will help in developing camomile as a promising therapeutic agent. Without such evidence, it will remain unclear whether these untested and unproven medical treatments are truly beneficial. It is advisable that the discriminate and proper use of camomile preparations could be safe and provide therapeutic benefits however the indiscriminate or improper use can be unsafe and harmful.

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What is neem

Neem (Azadirachta indica) is commonly known as Indian lilac, is a tree in the mahogany family Meliaceae. Neem is one of two species in the genus Azadirachta and is native to the Indian subcontinent, i.e. India, Nepal, Pakistan, Bangladesh, Sri Lanka, and Maldives. Neem typically is grown in tropical and semi-tropical regions, their large size and preference for wet areas. Neem trees now also grow in islands located in the southern part of Iran. Its fruits and seeds are the source of neem oil.

These features describe the habit of neem plant:

• fast growing tree can grow 12 to 24m high
• compound leaves 20 to 40cm long, made up of 20 to 30 leaflets and leaflets between 3 to 8cm long. Neem leaflets are vibrant yellowy green with distinctive toothed margins.
• Neem fruit are green, ripening to yellow. Neem fruits are similar to olives in size and shape.

All the parts of neem tree is commonly used in traditional Indian medicine for household remedy against various human diseases as well as pest control ¹, ², ³. Neem-based pesticides are now extensively used in agriculture practices all over the world. It contains azadirachtin, which is a predominant insecticidal active ingredient, having antefeedent, ovipositional deterrence repellency, growth disruption, sterility and larvicidal action against insects ⁴. There are various reports of control of mosquito breeding under field conditions. An emulsion of neem oil in water was found to be effective in controlling breeding of Culex quinquefasciatus (mosquito vector of Japanese encephalitis virus), Anopheles stephensi (mosquito vector of malaria in urban India) and Aedes aegypti larvae (larvae of the mosquito vector of Yellow fever virus & Dengue fever) in pools, tanks and coolers up to 2 to 3 weeks ⁵, whereas an application of neem cake powder resulted in drastic reduction in the late instar larvae and pupae of culicine mosquitoes in paddy field ⁶.

For centuries, millions of Indian have cleaned their teeth with neem twigs, smeared skin disorders with neem leaf juice, taken neem tea as a tonic, and placed neem leaves in their beds, books, grain bins, cupboards, and closets to keep away troublesome bugs. The tree has relieved so many different pains, fevers, infections, and other complaints so that it has been called “the village pharmacy” ⁷. In rural India, peoples often used water decoction of neem leaves for the prevention and treatment of various ailments.

Bioactive compounds in neem include: nimbidin, nimbolide, gedunin, mahmoodin, flavonoids, tannins, and alkaloids. These phytochemicals act on bacterial cell wall by binding to adhesins forming complex causing inactivation of proteins and cell function ⁸. Nimbidin has anti-inflammatory, anti-arthritic, antipyretic, hypoglycemic, and anti-bacterial property ⁹. It is active against Klebsiella, Staphylococcus, and Serratia species. It is also active against Streptococcus mutans and Streptococcus faecalis ¹⁰.

Neem is commonly seen as a medicinal tree and versatile plant having a wide spectrum of biological activities. Various studies have been put forward on its antimicrobial properties. A study by Elavarasu et al ¹¹ stated that neem oil was effective by reducing the growth of the plaque-causing microorganisms. Bohora et al ¹² found that neem extract showed significant antimicrobial effect against Enterococcus faecalis and Candida albicans. But a study by Kumar and Sidhu ¹³ stated that neem extract was ineffective and did not inhibit the growth of Enterococcus faecalis; similar negative result was obtained in another study ¹⁴.

Neem Weed status

Neem is considered a weed in many areas, including some parts of the Middle East, most of Sub-Saharan Africa including West Africa and Indian Ocean states, and some parts of Australia ¹⁵.

Figure 1. Neem

Neem Uses

Neem leaves are dried in India and placed in cupboards to prevent insects eating the clothes, and also in tins where rice is stored. Neem leaves are dried and burnt in the tropical regions to keep away mosquitoes. These flowers are also used in many Indian festivals like Ugadi. As an ayurvedic herb, neem is also used in baths.

As a vegetable

The tender shoots and flowers of the neem tree are eaten as a vegetable in India. A souplike dish called Veppampoo charu (Tamil) (translated as “neem flower rasam”) made of the flower of neem is prepared in Tamil Nadu. In Bengal, young neem leaves are fried in oil with tiny pieces of eggplant (brinjal). The dish is called nim begun and is the first item during a Bengali meal that acts as an appetizer. It is eaten with rice.

Neem is used in parts of mainland Southeast Asia, particularly in Cambodia, Laos (where it is called kadao), Thailand (where it is known as sadao or sdao), Myanmar (where it is known as tamar) and Vietnam. Even lightly cooked, the flavour is quite bitter and the food is not enjoyed by all inhabitants of these nations, though it is believed to be good for one’s health. In Myanmar, young neem leaves and flower buds are boiled with tamarind fruit to soften its bitterness and eaten as a vegetable. Pickled neem leaves are also eaten with tomato and fish paste sauce in Myanmar.

Head lice

An anti-louse shampoo (Licener®) based on a neem seed extract was tested in vivo and in vitro on its efficacy to eliminate head louse infestation by a single treatment. The hair of 12 children being selected from a larger group due to their intense infestation with head lice were incubated for 10 min with the neem seed extract-containing shampoo ¹⁶. It was found that after this short exposition period, none of the lice had survived, when being observed for 22 h. In all cases, more than 50-70 dead lice had been combed down from each head after the shampoo had been washed out with normal tap water. A second group of eight children had been treated for 20 min with identical results. Intense combing of the volunteers 7 days after the treatment did not result in the finding of any motile louse neither in the 10-min treated group nor in the group the hair of which had been treated for 20 min. Other living head lice were in vitro incubated within the undiluted product (being placed inside little baskets the floor of which consisted of a fine net of gauze). It was seen that a total submersion for only 3 min prior to washing 3× for 2 min with tap water was sufficient to kill all motile stages (larvae and adults). The incubation of nits at 30°C into the undiluted product for 3, 10, and 20 min did not show differences. In all cases, there was no eyespot development or hatching larvae within 7-10 days of observation. This and the fact that the hair of treated children (even in the short-time treated group of only 10 min) did not reveal freshly hatched larval stages of lice indicate that there is an ovicidal activity of the product, too.

Other uses

Insufficient evidence to rate effectiveness for:

• Skin diseases such as psoriasis, eczema, alopecia, diabetic ulcer, warts, vitiligo, pemphigus, pompholyx, leprosy, and many other more very common and rare diseases.
• Antisnake venom activity
• Digestive disorders
• Anticarcinogenic activity
• Antioxidant effect
• Anti-inflammatory activity
• Sexually transmitted disease
• Immune system
• Antiviral
• Antibacterial activity

Studies in human are to rate the effectiveness of neem or neem oil for these uses.

What is neem oil

Neem oil (margosa oil) is a vegetable oil obtained from the seed kernels of Neem tree (Azadirachta indica). Neem oil is deep yellow in color and has garlic–like odor. It contains active ingredients like azadirachtin, nimbin, picrin, and sialin.

Neem oil, as a traditional medical remedy, is used as anti-bacterial, anti-fungal, insect repellent, and treatment of skin diseases. Traditional routes of administration of Neem extracts included oral, vaginal, and topical use. Neem oil comprises mainly triglycerides, steroids (campesterol, beta-sitosterol, stigmasterol) and many triterpenoids, of which azadirachtin is the most well-known and studied. The azadirachtin content of neem oil varies from 300 ppm to over 2500 ppm, depending on the extraction technology and quality of the neem seeds crushed.

What is neem oil used for

One of the most extensively used “natural” plant derived insecticides is neem ⁴. The pesticide action of neem oil is attributed to azadirachtin, which is used as an insecticide for arthropod pests ¹⁷. Commercially available neem based insecticides are used to control many crop pests and this is considered as a “green” approach to pest control, permitted in organic production systems ¹⁸.

Neem oil was shown to be toxic to Anopheles stephensi (mosquito vector of malaria in urban India), Culex quinquefasciatus (mosquito vector of Japanese encephalitis virus) and Aedes aegypti larvae (larvae of the mosquito vector of Yellow fever virus & Dengue fever) with median lethal concentrations (LC50) of 1.6, 1.8 and 1.7 ppm respectively ¹⁹. The neem oil formulation tested by Dua and co-workers ¹⁹ was also found to be effective in controlling mosquito larvae under natural field conditions, which could be used as an alternative for malaria control.

Recently, entomopathogenic fungi have been formulated in neem oil and tested against larval and adult An. gambiae and adult C. quinquefasciatus ²⁰. The results showed that the formulation of fungus + neem was more effective than neem alone for adults and larvae. The “formulation” of fungus in water was not as effective as fungus formulated in neem oil against adults, although larvae were not exposed to formulations of fungus without neem ²⁰.

An emulsion of neem oil in water was found to be effective in controlling breeding of Culex quinquefasciatus, Anopheles stephensi and Aedes aegypti in pools, tanks and coolers up to 2 to 3 weeks ⁵, whereas an application of neem cake powder resulted in drastic reduction in the late instar larvae and pupae of culicine mosquitoes in paddy field ⁶.

Table 1. Larvicidal activity of neem oil formulation against mosquito in laboratory

Table 2. Larvicidal activity of neem oil formulation against mosquitoes larvae in field

Table 3. Larvicidal activity of neem oil formulation against Aedes mosquitoes in field

Neem oil poisoning

Neem oil has widespread use in Indian subcontinent due to its many bioactive properties. Neem oil poisoning is rare in adults. In children, neem oil is reported to cause toxic encephalopathy and Reye’s–like syndrome ²¹. Azadirachtin (C₃₅H₄₄O₁₆), a complex tetranortriterpenoid, is implicated in causing the effects seen in neem oil poisoning ²². Azadirachtin manifests its toxicity possibly by interfering with mitochondrial bioenergetics, resulting in inhibition of the generation of the electrochemical proton gradient (primary form of energy generated in mitochondria). Acute poisoning with inhibitors of electron transporting complexes causes symptoms such as muscle weakness, easy fatigability, hypotension, headache, facial flushing, nausea, confusion, and aggravation of latent myocardial angina. The inability to utilize oxygen is manifested as a cytotoxic hypoxia wherein the chemicals cause a metabolic acidosis and hyperpnea, despite normal pO2.

In children, there are several case reports of Neem oil poisoning causing vomiting, hepatic toxicity, metabolic acidosis, and encephalopathy ²³. Lai et al. ²⁴, reported 22 cases of neem oil poisoning in infants, who were given single doses of Neem oil (few drops to 5 ml), presented with features of toxic encephalopathy, metabolic acidosis, and hepatic toxicity. The infants recovered completely with supportive treatment ²⁴. Sundaravalli et al. ²³, in a case series of 12 children with neem oil poisoning, who were given single dose of Neem oil (25-60 ml), reported fatality in 10 cases with features of toxic encephalopathy and metabolic acidosis. Sinnaih et al. ²¹, reported Reyes–like syndrome in fatal cases of Neem oil poisoning in a case series of 13 children.

In adults, there are few case reports of Neem poisoning. A case report of neem oil poisoning involving a 73-year-old male who presented with vomiting, seizures, metabolic acidosis, and toxic encephalopathy – 1 hour after accidental ingestion of 20 ml of Neem oil ²⁵. The patient recovered completely with symptomatic treatment. Iyyaduria et al. ²², reported a case of a 35-year-old female with suicidal poisoning, who presented after ingestion of 250 ml of Neem pesticide with encephalopathy and metabolic acidosis with no evidence of hepatic and renal complications. She recovered completely with supportive management. Bhasker et al. ²⁶, reported a 35-year-female with Neem oil poisoning who presented with bilateral visual loss. Cranial MR imaging, showed symmetrical altered signal intensity bilaterally in the putamen region with extension to the posterior limb of the internal capsule. Laboratory findings were within normal limits, and she recovered completely with supportive management.

There is no specific antidote available, and gastric lavage is not recommended for Neem oil poisoning. The management is primarily symptomatic and recovery is usually complete ²⁷.

What is Reye Syndrome

Reye syndrome is a rare illness that can affect the blood, liver, and brain of someone who has recently had a viral infection ²⁸. It always follows another illness. Although it mostly affects children and teens, anyone can get it. It can develop quickly and without warning. It is most common during flu season.

Symptoms include

• Nausea and vomiting
• Listlessness
• Personality change – such as irritability, combativeness or confusion
• Delirium
• Convulsions
• Loss of consciousness

If these symptoms occur soon after a viral illness, seek medical attention immediately. Reye syndrome can lead to a coma and brain death, so quick diagnosis and treatment are critical. Treatment focuses on preventing brain damage. There is no cure.

Neem oil allergic contact dermatitis

Allergic contact dermatitis from neem oil has been described previously in 3 patients ²⁹. The allergen(s) is/are unknown.

Summary

Neem has been used as an herbal medication since ancient times, is still popular today and probably will continue to be used in the future because it contains various bioactive phytochemicals that could provide therapeutic effects.

Establishing whether or not therapeutic effects of neem are beneficial to patients will require good clinical research and generation of scientific evidence. There is a need for continued efforts that focuses on various diseases, which are then validated in clinical trials that will help in developing neem as a promising therapeutic agent. Without such evidence, it will remain unclear whether these untested and unproven medical treatments are truly beneficial. It is advisable that the discriminate and proper use of neem preparations could be safe and provide therapeutic benefits however the indiscriminate or improper use can be unsafe and harmful- e.g. neem current use as pesticide and to kill mosquitos larvae.

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17. Dhongade RK, Kavade SG, Damle RS. Neem oil poisoning. Indian Pediatr 2008;45:56–57. https://www.ncbi.nlm.nih.gov/pubmed/18250509[↩]
18. Gomes SA, Paula AR, Ribeiro A, et al. Neem oil increases the efficiency of the entomopathogenic fungus Metarhizium anisopliae for the control of Aedes aegypti (Diptera: Culicidae) larvae. Parasites & Vectors. 2015;8:669. doi:10.1186/s13071-015-1280-9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4696216/[↩]
19. Larvicidal activity of neem oil (Azadirachta indica) formulation against mosquitoes. Dua VK, Pandey AC, Raghavendra K, Gupta A, Sharma T, Dash AP. Malar J. 2009 Jun 8; 8():124. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2702347/[↩][↩][↩][↩][↩]
20. Seye F, Ndione D, Touré M, Ndiaye M, Boukraa S, Bawin T, Zimmer J-Y, Francis F. Laboratory and semi-field environment tests for the control efficacy of Metarhizium anisopliae formulated with neem oil (suneem) against Anopheles gambiae s.l. adult emergence. Acad J Biotech. 2013;1:046–052.[↩][↩]
21. Margosa oil poisoning as a cause of Reye’s syndrome. Sinniah D, Baskaran G. Lancet. 1981 Feb 28; 1(8218):487-9. https://www.ncbi.nlm.nih.gov/pubmed/6110100/[↩][↩]
22. Azadirachtin poisoning: a case report. Iyyadurai R, Surekha V, Sathyendra S, Paul Wilson B, Gopinath KG. Clin Toxicol (Phila). 2010 Oct; 48(8):857-8. https://www.ncbi.nlm.nih.gov/pubmed/20932102/[↩][↩]
23. Neem oil poisoning. Sundaravalli N, Raju BB, Krishnamoorthy KA. Indian J Pediatr. 1982 May-Jun; 49(398):357-9. https://www.ncbi.nlm.nih.gov/pubmed/7141505/[↩][↩]
24. Margosa oil poisoning as a cause of toxic encephalopathy. Lai SM, Lim KW, Cheng HK. Singapore Med J. 1990 Oct; 31(5):463-5. https://www.ncbi.nlm.nih.gov/pubmed/2259944/[↩][↩]
25. Mishra A, Dave N. Neem oil poisoning: Case report of an adult with toxic encephalopathy. Indian Journal of Critical Care Medicine : Peer-reviewed, Official Publication of Indian Society of Critical Care Medicine. 2013;17(5):321-322. doi:10.4103/0972-5229.120330. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3841499/[↩]
26. MR imaging findings of neem oil poisoning. Bhaskar MV, Pramod SJ, Jeevika MU, Chandan PK, Shetteppa G. AJNR Am J Neuroradiol. 2010 Aug; 31(7):E60-1. http://www.ajnr.org/content/31/7/E60.long[↩]
27. Neem oil poisoning. Dhongade RK, Kavade SG, Damle RS. Indian Pediatr. 2008 Jan; 45(1):56-7. https://www.ncbi.nlm.nih.gov/pubmed/18250509/[↩]
28. Reye syndrome. https://medlineplus.gov/reyesyndrome.html[↩]
29. Contact Allergy to Neem Oil. http://journals.lww.com/dermatitis/Abstract/publishahead/Contact_Allergy_to_Neem_Oil.99783.aspx[↩]

What is wheatgrass

Wheatgrass is a food prepared from the freshly sprouted first leaves of the young grass of the common wheat plant Triticum aestivum ¹. Wheatgrass consumption in the Western world began in the 1930s. Today, wheatgrass is quickly becoming one of the most widely used supplemental health foods and is available in many health food stores as fresh produce, tablets, frozen juice, and powders, with compositions varying according to their production processes, as well as to the growing conditions of the wheatgrass. Because wheatgrass juice is extracted from wheatgrass sprouts, i.e., before the wheat seed begins to form, it is gluten-free. Wheatgrass differs from wheat malt in that it is served freeze-dried or fresh, while wheat malt is convectively dried. Wheatgrass is allowed to grow longer than malt. Like most plants, it contains chlorophyll, amino acids, minerals (iron, calcium, and magnesium), vitamin A, vitamin C, vitamin E, flavonoids and enzymes ². Kulkarni et al ³ reported that wheatgrass juice has high antioxidant activity partly because it contains such antioxidants as phenolic compounds and several flavonoids. Phenolics and flavonoids have been shown to remove superoxide radicals (O₂⁻ or HO₂⁻) in vivo and decrease the cell damage caused by oxidative stress ⁴. Wheatgrass extracts also possess superoxide scavenging and ferric reducing abilities ⁵. Their ability to inhibit oxidative DNA damage was also demonstrated ⁶. Claims about the health benefits of wheatgrass range from providing supplemental nutrition to having unique curative properties, but these claims have not been scientifically proven ¹. Furthermore, there is no sound evidence to support the claim that wheatgrass is better than other fruits and vegetables in terms of nutrition. It cannot be recommended above any other choices in this food group.

Wheatgrass juice is often available in juice bars, and some consumers grow and juice wheatgrass in their homes. Wheatgrass is available as fresh produce, tablets, frozen juice and powder. Wheatgrass is also available commercially as a spray, cream, gel, massage lotion, and a liquid herbal supplement. No adverse events of wheatgrass have been reported, although some forms pose problems of tolerability.

Wheatgrass nutrition facts

Table 1. Wheatgrass juice nutrition facts

Wheatgrass health benefits

Antileukemic potential

In a test tube study ⁸, methanol extract of wheat grass demonstrated antileukemic potential that might be due to the presence of flavonoids and polyphenolics in it. Flavonoids and polyphenols are important class of phytoconstituents, which are found in fruits and vegetables. In that test tube study ⁸, wheatgrass extract was found to be rich in flavonoids and polyphenols. Flavonoids are known to inhibit the activity of “angiogenic mediators” and provoke “apoptosis,” they also exert “antiproliferative” effect on leukemic cells ⁹. Quercetin and flavopiridol have demonstrated antiproliferative effects on leukemic cells ¹⁰. Some other flavonoids such as genistein, honokiol, machilin A, matairesinol, and arctigenin have also shown lethal effects on leukemia cell lines ¹¹.

Ulcerative colitis

Wheat grass juice vs. placebo was compared in a randomized double-blind study ¹² in patients with active ulcerative colitis; 24 patients were evaluated by means of disease activity, symptoms severity, and adverse events. After 4 weeks of wheat grass juice administration, of the 21 patients who completed the study, treatment with wheat grass juice was associated with significant reductions in the overall disease activity and in the severity of rectal bleeding and less abdominal pain ¹². No serious side effects were found, but analysis did not include drop-outs, and follow-up was too short. However, the study involved only 21 people and the positive results could have been simply down to chance. As such, the evidence is inconclusive.

Can wheatgrass help people with blood disorders ?

A small Indian study ¹³ from 2004 of 32 patients with a blood disorder called thalassaemia found half of the patients required fewer blood transfusions when 100ml (3.5oz) of wheatgrass juice was taken daily for three years. While interesting, the research has many weaknesses and further research is needed before these findings can be properly validated.

Can drinking wheatgrass boost red blood cell production ?

Fans of wheatgrass believe that because chlorophyll and haemoglobin (a protein that carries oxygen around your body) are similar in structure, taking wheatgrass juice enhances haemoglobin production. But as far as evidence goes, there is no scientific proof to support this claim.

Nutrition claims for wheatgrass

Despite claims that a 30ml (1oz) shot of wheatgrass contains as many nutrients as 1kg (2.2lbs) of your finest veggies, tests show that, pound for pound, the nutrient content of wheatgrass juice is roughly equivalent to that of common vegetables, such as spinach and broccoli.

1. The Medical Use of Wheatgrass: Review of the Gap Between Basic and Clinical Applications. Mini-Reviews in Medicinal Chemistry Volume 15, Issue 12, 2015. DOI: 10.2174/138955751512150731112836, http://www.eurekaselect.com/133683/article[↩][↩]
2. Peryt, B., Szymczy, K.T., and Lesca, P. Mechanism of antimutagenicity of wheat sprout extracts. Mutat Res. 1992; 269: 201–205. http://www.sciencedirect.com/science/article/pii/002751079290201C[↩]
3. Kulkarni, S.D., Acharya, R., Nair, A.G.C., Rajurkar, N.S., and Reddy, A.V.R. Determination of elemental concentration profiles in tender wheatgrass (Triticum aestivum L.) using instrumental neutron activation analysis. Food Chem. 2006; 95: 699–707[↩]
4. Cao, G., Sofic, E., and Prior, R.L. Antioxidant capacity of tea and common vegetables. J Agric Food Chem. 1996; 44: 3426–3431[↩]
5. Peryt, B., Szymczy, K.T., and Lesca, P. Mechanism of antimutagenicity of wheat sprout extracts. Mutat Res. 1992; 269: 201–205[↩]
6. Falcioni, G., Fedeli, D., Tiano, L., Calzuola, I., Mancinelli, L., Marsili, V., and Gianfranceschi, G. Antioxidant activity of wheat sprout extracts in vitro: inhibition of DNA oxidative damage. J Food Sci. 2002; 67: 2918–2922[↩]
7. United States Department of Agriculture Agricultural Research Service. USDA Branded Food Products Database. https://ndb.nal.usda.gov/ndb/search/list[↩]
8. Khan N, Ganeshpurkar A, Dubey N, Bansal D. Immunoprophylactic potential of wheat grass extract on benzene-induced leukemia: An in vivo study on murine model. Indian Journal of Pharmacology. 2015;47(4):394-397. doi:10.4103/0253-7613.161261. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4527060/[↩][↩]
9. Faderl S, Estrov Z. Commentary: Effect of flavonoids on normal and leukemic cells. Leuk Res. 2003;27:471–3. https://www.ncbi.nlm.nih.gov/pubmed/12648504[↩]
10. Liesveld JL, Abboud CN, Lu C, McNair C, Menon A, Smith A, et al. Flavonoid effects on normal and leukemic cells. Leuk Res. 2003;27:517–27. https://www.ncbi.nlm.nih.gov/pubmed/12648512[↩]
11. Hirano T, Gotoh M, Oka K. Natural flavonoids and lignans are potent cytostatic agents against human leukemic HL-60 cells. Life Sci. 1994;55:1061–9. https://www.ncbi.nlm.nih.gov/pubmed/8084211[↩]
12. Wheat grass juice in the treatment of active distal ulcerative colitis: a randomized double-blind placebo-controlled trial. Scand J Gastroenterol. 2002 Apr;37(4):444-9. https://www.ncbi.nlm.nih.gov/pubmed/11989836[↩][↩]
13. Wheat grass juice reduces transfusion requirement in patients with thalassemia major: a pilot study. Indian Pediatr. 2004 Jul;41(7):716-20. http://www.indianpediatrics.net/july2004/july-716-720.htm [↩]

What is milk thistle

Milk thistle is an annual or biennial herb native to the Mediterranean region, Silybum marianum (L) Gaertneri, named for the white veins on its large prickly leaves. Milk thistle is also referred to as holy thistle, Marian thistle, Mary thistle, Our Lady’s thistle, St. Mary thistle, wild artichoke, Mariendistel (German), and Chardon-Marie (French). Traditionally, the leaves have been used in salads, and the fruit of the flower has been roasted as a coffee substitute. The seed-like fruits (achenes) of milk thistle are the medicinal parts of the plant, which contain approximately 4–6% silymarin ¹. The extract consists of about 65–80% silymarin (a flavonolignan complex) and 20–35% fatty acids, including linoleic acid ². The active substance in milk thistle, silymarin, is a complex mixture of flavonolignans. Silymarin’s primary constituents are the flavonolignan isomers silybins A and B, isosilybin A and B, silychristin (also known as silichristin), silydianin (also known as silidianin), and their flavonoid precursor, taxifolin. In the literature, the mixture of the silybins A and B is often referred to as silibinin ², ³. Silibinin, a semipurified fraction of silymarin, is primarily a mixture of 2 diastereoisomers, silybin A and silybin B, in a roughly 1:1 ratio ⁴. Laboratory studies demonstrate that silymarin stabilizes cellular membranes, stimulates detoxification pathways, stimulates regeneration of liver tissue, inhibits the growth of certain cancer cell lines, exerts direct cytotoxic activity toward certain cancer cell lines, and possibly increases the efficacy of certain chemotherapy agents.

Figure 1. Milk thistle

The extracts of milk thistle, have been used as medical remedies since the time of ancient Greece and the extracts are now widely used as an alternative medication ⁵. Milk thistle extracts have been shown to protect animals against various hepatotoxins including acetaminophen ⁶, radiation ⁷, iron overload ⁸, phalloidin ⁹, carbon tetrachloride ¹⁰, and thioacetamide ¹¹. The ‘hepatoprotective’ actions of milk thistle may include inhibition of lipid peroxide formation, scavenging of free radicals, and changing of the physical properties of cell membranes ¹². Milk thistle may also reduce liver fibrogenesis ¹³. According to a recent meta-analysis on milk thistle for patients with liver diseases no significant reduction in mortality or improvements in liver histology, or liver function could be demonstrated, but data were too limited to exclude a substantial benefit or harm of milk thistle on mortality (Lawrence 2000; Jacobs 2002). Accordingly, there is insufficient evidence to support or refute recommending this herbal compound to patients for the treatment of liver diseases (Lawrence 2000; Jacobs 2002). However, this 2007 Cochrane systematic review ¹⁴ involving thirteen randomised clinical trials assessing milk thistle in 915 patients with alcoholic and/or hepatitis B or C virus liver diseases could not demonstrate significant effects of milk thistle on mortality or complications of liver diseases in patients with alcoholic and/or hepatitis B or C liver diseases combining all trials or high-quality trials. Low-quality trials suggested beneficial effects, but this effect could not be demonstrated in high-quality trials. As the methodological quality of the majority of the trials was low, bias and/or random errors may explain some or all of the positive findings. Furthermore, these effects could neither be confirmed in a subgroup analysis including patients with alcoholic liver disease coinfected by hepatitis C virus (HCV) nor in a worst-case scenario analysis. Therefore the findings are not robust enough to form a foundation for therapeutic recommendations. On the positive side, milk thistle did not differ significantly from placebo/no intervention regarding adverse events. Therefore at the present time, there is insufficient evidence to support or refute milk thistle for patients for the treatment of alcoholic liver diseases. The reviewers suggested high-quality randomized clinical trials on milk thistle versus placebo are needed ¹⁴.

What is milk thistle good for

The major constituents of silymarin are the three diastereomeric pairs, silybins A and B (also called silibinin), isosilybins A and B, silychristin, isosilychristin, and silydianin ¹⁵. Most supplements are standardized according to their silybin content. Special formulations of silymarin and/or the silybins have been developed to enhance their bioavailability by conjugation with phosphatidylcholine. Because of the lipophilic nature of its active constituents, milk thistle is usually administered as an extract in capsule or tablet form rather than as an herbal tea. In Europe, silybin is administered intravenously as the only effective antidote for Amanita phalloides (Fr.) ¹⁶. Humans exposed to this mushroom toxin develop serious liver failure that progresses to death.

Several companies distribute milk thistle as a dietary supplement. In the United States, dietary supplements are regulated as foods, not drugs. Therefore, premarket evaluation and approval by the U.S. Food and Drug Administration (FDA) are not required unless specific disease prevention or treatment claims are made. Because dietary supplements are not formally reviewed for manufacturing consistency, ingredients may vary considerably from lot to lot; in addition, there is no guarantee that ingredients identified on product labels are present at all or are present in the specified amounts. The FDA has not approved the use of milk thistle as a treatment for cancer patients or patients with any other medical condition.

Despite milk thistle’s long history of being used to treat liver and biliary complaints, it was not until 1968 that silymarin was isolated from the seeds of the plant, and it was proposed that silymarin might be the active ingredient ¹⁷. Researchers have investigated the role that silibinin may play in the treatment of hepatitis and cirrhosis. Most studies have investigated the isolated compound silymarin or its most active isomer silybin, rather than the herbal plant in its whole form.

Silymarin is most well known for its purported effects on the liver. In laboratory studies, silymarin has been found to stabilize cell membranes, thus preventing toxic chemicals from entering the cell ¹⁸. Laboratory studies have also demonstrated that silymarin stimulates synthesis and activity of enzymes responsible for detoxification pathways ¹⁹. Specifically, silymarin has been shown to stimulate the glutathione S-transferase pathway and alter the intracellular concentration of glutathione (a potent antioxidant). Silymarin has also been shown to neutralize a wide range of free radicals. Reports that associate the flavonolignans with potential estrogenic effect (e.g., via mediation of the estrogen receptor) are sparse and currently not supported by in vitro or in vivo experimental evidence ²⁰.

Laboratory experiments conducted using cancer cell lines have suggested that silibinin enhances the efficacy of cisplatin and doxorubicin against ovarian and breast cancer cells ²¹. Silybin appears to have direct anticancer effects against prostate, breast, and ectocervical tumor cells ²². Silybin may also affect the cell cycle in cancer cells by slowing down cell growth, as demonstrated with prostate cancer cell lines ²³. Laboratory studies using leukemia cell lines found that silybin did not stimulate growth of leukemia cells ²⁴.

Most clinical trials have investigated silymarin’s effectiveness in the treatment of patients with hepatitis, cirrhosis, or biliary disorders ²⁵. These studies have employed a wide range of doses (120–560 mg /day) and have yielded conflicting results ²⁶, ²⁷. The most commonly reported adverse effects are a mild laxative effect and gastrointestinal upset.

Several small studies have investigated silymarin for its direct treatment of cancer or for its effects on treatment-related toxicity.

A phase I study was designed to determine the maximum tolerated dose per day of silybin phosphatidylcholine (Siliphos) in patients with advanced hepatocellular carcinoma (HCC) and hepatic dysfunction ²⁸. Three patients were enrolled in this single-institution trial. All patients who were enrolled consumed 2 g /d of the study agent in divided doses. Serum concentrations of silibinin and silibinin glucuronide increased within 1 to 3 weeks. In all three patients, liver function abnormalities and tumor marker alpha-fetoprotein progressed, but after day 56, the third patient showed some improvement in liver function abnormalities and inflammatory biomarkers. All three patients died within 23 to 69 days of enrolling in the trial, likely from hepatic failure, but it could not be ruled out that deaths were possibly caused by the study drug. This patient population may have been too ill to benefit from an intervention designed to improve liver function tests.

In a double-blind, placebo-controlled trial, 50 children who were undergoing treatment for acute lymphoblastic leukemia, and who had chemotherapy -related hepatotoxicity, were randomly assigned to receive silymarin or placebo for a 4-week period ²⁹. Four weeks after completion of the intervention, the silymarin group had a significantly lower aspartate aminotransferase (AST) and a trend towards a significantly lower alanine aminotransferase (ALT). Fewer chemotherapy dose reductions were observed in the silymarin group compared with the placebo group; however, the difference was not significant. No adverse events were reported.

A randomized placebo-controlled study of 37 men, who had a status of post–radical prostatectomy, investigated whether a 6-month daily administration of a silymarin and selenium combination would alter basic clinical chemistry, oxidative stress markers, and improve the quality-of-life (QOL) score in men after radical prostatectomy ³⁰. The 6-month daily administration of silymarin and selenium improved the QOL score, decreased low-density lipoproteins and total cholesterol, and increased serum selenium levels. The combination had no effect on blood antioxidant status and no influence on testosterone level. No adverse events were recorded. No improvement was found in the placebo group.

Another randomized placebo-controlled study of 30 patients with head and neck cancer investigated a 6-week course of silymarin for the prevention of radiation therapy –associated mucositis. Mucositis scores (World Health Organization, National Cancer Institute Common Toxicity Criteria) were significantly lower in the silymarin group ³¹. Delay in progression to mucositis was also observed.

In a nonrandomized observational trial of 101 women with breast cancer who had undergone breast-conserving surgery followed by radiation therapy with 50.4 Gy plus a boost of 9 Gy to 16 Gy, a silymarin-based cream (Leviaderm) was tested in 51 women compared with panthenol-containing cream, the standard of care (SOC), which was given interventionally if local skin lesions occurred and administered to 50 women ³². The acute skin reactions were classified according to the Radiation Therapy Oncology Group and visual analog scale scores. The median time to toxicity was prolonged significantly with the silymarin-based cream (45 vs. 29 days SOC). Only 9.8% of patients using the silymarin-based cream showed grade 2 toxicity in week 5 of radiation therapy, compared with 52% in the SOC group. At the end of radiation therapy, 23.5% of the women in the silymarin-based study group developed no skin reactions compared with 2% of the women in the SOC group, while grade 3 toxicity occurred in only 2% of women in the silymarin-based group and in 28% of women in the SOC group.

Chronic Hepatitis C Infection

There has been skepticism regarding the evidence that silymarin has a direct impact on the hepatitis C virus (HCV)—some studies suggest that it does, but most studies cannot confirm these reports. However, at least two articles in major journals have suggested that silymarin or its congeners may inhibit hepatitis C virus (HCV). In one report, investigators found that a standardized silymarin extract inhibited tumor necrosis factor -alpha in anti-CD3–stimulated human peripheral blood mononuclear cells and nuclear factor-kappa B –dependent transcription in human hepatoma Huh-7 cells ³³. Silymarin also displayed prophylactic and therapeutic effects against HCV infection, and when combined with interferon-alpha, was more inhibitory of HCV replication than was interferon alone. This indicates that silymarin has anti-inflammatory and antiviral effects in patients with chronic hepatitis C.

Silymarin (Silybum marianum), an extract of milk thistle, is the botanical treatment most commonly used for liver disorders in the United States, owing to its purported hepatoprotective properties ³⁴. Indeed, 33% of patients with chronic hepatitis C virus (HCV) infection and cirrhosis reported current or past use of silymarin for the treatment of their disease ³⁵. Silymarin has been demonstrated to have anti-inflammatory and immunomodulatory properties via inhibition of NF-κB (nuclear factor κ-light-chain-enhancer of activated B cells), as demonstrated in vitro ³⁶. Studies of silymarin in the hepatitis C virus replicon system also suggest an effect on hepatitis C virus core and NS5A expression, although at high concentrations ³⁷. These same pathways, implicated in the pathogenesis of chronic liver disease, provide the rationale to investigate silymarin as a potential treatment for chronic hepatitis C virus infection.

A 2008 Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) randomized, controlled trial supported by the National Institute of Diabetes and Digestive and Kidney Diseases examined patients with chronic hepatitis C who had failed previous antiviral therapy. All patients had advanced chronic liver disease consisting of histologic evidence of either marked fibrosis or cirrhosis. The Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis trial used a half dose of pegylated interferon versus no treatment; the treatment was to be administered for 3.5 years ³⁸. The aim was to reduce progression of chronic hepatitis C, particularly in the development of liver cancer. Among 1,145 study participants, 56% had never taken herbal products, 21% admitted past use, and 23% were using herbal products at enrollment. Silymarin constituted 72% of the 60 herbal products used at enrollment. Users had significantly fewer symptoms and a better quality of life than did nonusers. In follow-up, silymarin use was associated with reduced progression of fibrosis to cirrhosis but without an impact on clinical outcome ³⁹.

A 2012 clinical trial, involving 154 patients with chronic hepatitis C virus infection were randomly allocated to receive 420-mg silymarin, 700-mg silymarin, or matching placebo gelatin capsules administered 3 times daily for 24 weeks ⁴⁰. Most participants were men (71%); the median age was 54 years, and the median body mass index was 29.2 kg/m². The majority of patients had hepatitis C virus genotype 1 infection (91%). The median hepatitis C virus RNA level was 6.2 log10 IU/L and was similar in the 3 treatment groups. Serum ALT levels did not differ significantly (median, 106 U/L for placebo; 110 U/L for 420-mg silymarin; and 105 U/L for 700-mg silymarin) across treatment groups. Markers suggestive of advanced liver disease (serum bilirubin levels, albumin levels, platelet counts) did not differ significantly across treatment groups. This standardized silymarin product and dosage is approved as a prescription drug in several countries of Europe and Asia as a treatment for hepatic disorders. The primary outcome measure for efficacy was serum ALT level of 45 U/L or less (approximate normal range) or attainment of at least 50% decline of serum ALT level to less than 65 U/L (approximately 1.5 times the upper limit of normal) after the 24-week treatment period. The change in serum ALT level was chosen as the primary outcome in this study as a practical measure that has been correlated with improvement in hepatic necroinflammatory activity during studies of interferon for hepatitis C virus infection ⁴¹. Secondary outcomes included change in serum ALT and serum hepatitis C virus RNA levels during treatment. Adherence to study medication was assessed by dose counts.

At the end of treatment, 5 participants achieved serum ALT activity less than 45 U/L; 1 in the placebo group and 2 each in the 420-mg silymarin and 700-mg silymarin. One other participant treated with placebo had a decrease of serum ALT levels to less than 65 U/L, which reflected a decrease of 57% from baseline. Thus, 2 participants in each treatment group achieved the prespecified primary end point. The percentages of participants who achieved the primary end point were 3.8% in the placebo group, 4.0% in the 420-mg silymarin group, and 3.8% in the 700-mg silymarin group. In conclusion, the researchers found that silymarin did not significantly improve serum ALT levels – no change in virus activity or liver inflammation – compared with placebo when administered to patients with chronic hepatitis C virus infection previously unsuccessfully treated with interferon-based therapy ⁴⁰.

Iron Chelation for beta-Thalassemia major

Silymarin was found to be beneficial as an adjunct to the iron chelator desferrioxamine in patients with transfusion -dependent beta-thalassemia major ⁴². In a study of 97 patients, significant decreases in markers of iron overload (serum ferritin, serum iron, hepcidin, and soluble transferring receptor) were observed in the patients who received silymarin as compared with those who received a placebo.

This 2013 clinical study ⁴² shows that silymarin is effective at reducing iron overload in young people with a particular form of anemia (Cooley’s anemia or β-thalassemia) when used in conjunction with desferrioxamine. Therapeutic effects of silymarin on a background of desferrioxamine suggest the potential effectiveness of silymarin alone in reducing body iron burden. In that study patients were treated with the combination of desferrioxamine and silymarin (Legalon(®) ; n = 49) or desferrioxamine plus placebo (n = 48) for 9 months. The serum levels of ferritin, iron, total iron-binding capacity (TIBC), soluble transferrin receptor, and hepcidin were determined at the baseline and after 9-month therapy. Liver function test was performed before and after treatment in both groups. After 9 months of treatment, serum ferritin levels decreased significantly from the beginning to the end of silymarin treatment (3028.8 ± 2002.6 vs. 1972.2 ± 1250.6 ng/mL); however, no significant change in serum ferritin was observed in the patients receiving placebo (2249.0 ± 1304.2 vs. 2015.6 ± 1146.8). Moreover, serum iron and TIBC levels were significantly reduced in silymarin group compared with placebo. Patients on silymarin therapy also exhibited a significant decrease in serum levels of hepcidin and soluble transferrin receptor after 9-month treatment period. A significant improvement in liver function test was observed in silymarin group in comparison with placebo ⁴². This study shows that silymarin is effective at reducing iron overload in patients when used in conjunction with desferrioxamine. Therapeutic effects of silymarin on a background of desferrioxamine suggest the potential effectiveness of silymarin alone in reducing body iron burden.

Mushroom Poisoning

Another published report describes the use of silibinin as the only effective antidote in patients with liver damage from Amanita phalloides (Fr.) poisoning ⁴³. Patients were administered doses of 35 to 55 mg/kg of body weight, with no reports of adverse events. A retrospective review of the treatment for Amanita phalloides (Fr.) poisoning suggests that silymarin has been shown to be an effective drug in the treatment of this mushroom poisoning ⁴⁴. The beneficial effect of silymarin on liver histology suggests it has a role in the prevention of hepatitis and/or hepatocellular carcinoma (HCC); however, no clinical trials in humans have investigated these uses of silymarin.

Milk thistle side effects

Milk thistle has not been implicated in causing liver injury and appears to be safe when taken in appropriate doses and might play a role in treating certain liver conditions ⁴⁵.

Taken in appropriate doses, oral use of milk thistle appears to be safe ⁴⁶.

Human studies of silymarin have shown minimal adverse effects in multiple large, blinded, placebo-controlled, randomized studies. Silymarin is well tolerated, with only rare reports of a mild laxative effect. Mild allergic reactions have been seen at high doses (>1,500 mg /day), although the details of these allergic reactions were not reported. A case report from Australia described a reaction to a milk thistle extract that included intermittent episodes of sweating, abdominal cramping, nausea, vomiting, diarrhea, and weakness ⁴⁷. All symptoms resolved when the silymarin was discontinued. The authors suggested that the capsules were contaminated; the type of contamination was unknown.

According to the German Commission E, there are no reported side effects with milk thistle when the recommended doses are used. Rare cases of milk thistle producing a laxative effect have been reported. Human studies have reported stomach upset, heartburn, and transient headaches; however, none of these symptoms were attributed to supplementation with milk thistle, and supplementation was not discontinued ⁴⁸. One human dosing study reported nausea, heartburn, and dyspepsia in patients treated with 160 mg/day, dyspepsia in patients treated with 240 mg/day, and postprandial nausea and meteorism in patients treated with 360 mg/day. None of these side effects were dose related.

Silymarin has been well tolerated in high doses. Silymarin has been used in pregnant women with intrahepatic cholestasis at doses of 560 mg/day for 16 days, with no toxicity to the patient or the fetus ⁴⁹. The published data on silymarin use in children focuses on intravenous doses of 20 to 50 mg/kg of body weight for mushroom poisoning ⁴³. Silymarin has also proved nontoxic in rats and mice when administered in doses as high as 5,000 mg/kg of body weight. Rats and dogs have received silymarin at doses of 50 to 2,500 mg/kg of body weight for a 12-month period. Investigations, including postmortem analyses, showed no evidence of toxicity.

It is not known whether milk thistle may reduce, enhance, or have no impact on the effectiveness of chemotherapy. In vitro studies show that silymarin decreases the components of the cytochrome P450 enzyme system, which is involved in the clearance of certain chemotherapy drugs ⁵⁰. However, the dose at which inhibition is observed is high and not achieved with oral intake of silymarin ⁵¹. One study investigated the effects of silymarin on the pharmacokinetics of irinotecan. Oral administration of milk thistle (200 mg, a clinically relevant dose, 3 times per day) had no significant effects on the pharmacokinetics of irinotecan. The authors concluded that the recommended doses of milk thistle are too low to affect activity of CYP3A4 or UGT1A1 enzyme pathways ⁵².

Theoretically, milk thistle may also interact adversely with chemotherapy drugs that exert their cytotoxic effects through the generation of free radicals. Silymarin and its metabolite inhibit p-glycoprotein–mediated cellular efflux, leading to the potentiation of doxorubicin cytotoxicity ⁵³. No trials have been performed to support or negate these theoretical considerations. No effects on indinavir and alcohol pharmacokinetics have been observed. Enhancement of the antiarrhythmic effects of amiodarone in rats has been observed ⁵⁴.

Milk thistle can cause:

• Gastrointestinal issues
• Itchiness
• Headache

If you have diabetes, use milk thistle with caution, since the supplement might lower blood sugar. There is also concern that milk thistle might have estrogenic effects. If you have breast cancer, uterine cancer, ovarian cancer, endometriosis or uterine fibroids, consider avoiding milk thistle.

Milk thistle can cause an allergic reaction, including a severe, potentially life-threatening allergic reaction (anaphylaxis). An allergic reaction is more common in people who are allergic to other plants in the asteraceae family, such as ragweed, daisies, marigolds and chrysanthemums.

Milk thistle Interactions

Possible interactions include:

• Cytochrome P450 2C9 (CYP2C9) substrates. Taking milk thistle might affect this enzyme and drugs it processes, such as diazepam (Valium), warfarin (Coumadin, Jantoven) and others.
• Diabetes medications. Milk thistle might lower blood sugar in people who have type 2 diabetes. Taking milk thistle with diabetes drugs might cause additive effects. Closely monitor your blood sugar levels.
• Metronidazole (Flagyl). Milk thistle might reduce the effectiveness of this antibiotic. Avoid using milk thistle and metronidazole together.
• Simeprevir (Olysio). Taking milk thistle with this hepatitis C medication might increase the concentrations of the drug in your blood plasma. Avoid using milk thistle and simeprevir together.
• Sirolimus (Rapamune). Taking milk thistle with this immunosuppressant might change the way your body processes the medication.

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What to do for a bee sting

Bee stings are a common outdoor nuisance. In most cases, bee stings are just annoying, and home treatment is all that’s necessary to ease the pain of bee stings. But if you’re allergic to bee stings or you get stung numerous times, you may have a more-serious reaction that requires emergency treatment ¹.

• Call your local emergency number and services if you’re having a serious reaction to a bee sting that suggests anaphylaxis, even if it’s just one or two signs or symptoms. If you were prescribed an emergency epinephrine autoinjector (EpiPen, Auvi-Q, others), use it right away as your doctor directed.

You can take several steps to avoid bee stings — as well as hornet and wasp stings — and find out how to treat them if you do get stung.

Symptoms of a Bee sting

Bee stings can produce different reactions, ranging from temporary pain and discomfort to a severe allergic reaction. Having one type of reaction doesn’t mean you’ll always have the same reaction every time you’re stung, or that the next reaction will necessarily be more severe.

Mild reaction

Most of the time, bee sting symptoms are minor and include:

• Instant, sharp burning pain at the sting site
• A red welt at the sting area
• Slight swelling around the sting area

In most people, the swelling and pain go away within a few hours.

Moderate reaction

Some people who get stung by a bee or other insect have a bit stronger reaction, with signs and symptoms such as:

• Extreme redness
• Swelling at the site of the sting that gradually enlarges over the next day or two

Moderate reactions tend to resolve over five to 10 days. Having a moderate reaction doesn’t mean you’ll have a severe allergic reaction the next time you’re stung. But some people develop similar moderate reactions each time they’re stung. If this happens to you, talk to your doctor about treatment and prevention, especially if the reaction becomes more severe each time.

Severe allergic reaction

A severe allergic reaction (anaphylaxis) to bee stings is potentially life-threatening and requires emergency treatment. A small percentage of people who are stung by a bee or other insect quickly develop anaphylaxis. Signs and symptoms of anaphylaxis include:

• Skin reactions, including hives and itching and flushed or pale skin
• Difficulty breathing
• Swelling of the throat and tongue
• A weak, rapid pulse
• Nausea, vomiting or diarrhea
• Dizziness or fainting
• Loss of consciousness

People who have a severe allergic reaction to a bee sting have a 30 to 60 percent chance of anaphylaxis the next time they’re stung. Talk to your doctor or an allergy specialist about prevention measures such as immunotherapy (“allergy shots”) to avoid a similar reaction in case you get stung again.

Multiple bee stings

Generally, insects such as bees and wasps aren’t aggressive and only sting in self-defense. In most cases, this results in one or perhaps a few stings. In some cases a person will disrupt a hive or swarm of bees and get multiple stings. Some types of bees — such as Africanized honeybees — are more likely than are other bees to swarm, stinging in a group.

If you get stung more than a dozen times, the accumulation of venom may induce a toxic reaction and make you feel quite sick. Signs and symptoms include:

• Nausea, vomiting or diarrhea
• Headache
• A feeling of spinning (vertigo)
• Convulsions
• Fever
• Dizziness or fainting

Multiple stings can be a medical emergency in children, older adults, and people who have heart or breathing problems.

When to see a doctor

In most cases, bee stings don’t require a visit to your doctor. In more-severe cases, you’ll need immediate care – call your local emergency number.

Causes of bee sting

To sting, a bee jabs a barbed stinger into the skin. Bee sting venom contains proteins that affect skin cells and the immune system, causing pain and swelling around the sting area. In people with a bee sting allergy, bee venom can trigger a more-serious immune system reaction.

Risk factors for bee sting

You’re at increased risk of bee stings if:

• You live in an area where bees are especially active or with beehives nearby
• Your work or hobbies require spending time outside

You’re more likely to have an allergic reaction to bee stings if you’ve had an allergic reaction to a bee sting in the past, even if it was minor.

Adults tend to have more-severe reactions than children do and are more likely to die of anaphylaxis than children are.

Prevention of bee sting

The following tips can help reduce your risk of getting stung by bees:

• Take care when drinking sweet beverages outside. Wide, open cups may be your best option because you can see if a bee is in them. Inspect cans and straws before drinking from them.
• Tightly cover food containers and trash cans.
• Clear away garbage, fallen fruit, and dog or other animal feces (flies can attract wasps).
• Wear close-toed shoes when walking outside.
• Don’t wear bright colors or floral prints, which can attract bees.
• Don’t wear loose clothing, which can trap bees between the cloth and your skin.
• When driving, keep your windows rolled up.
• Be careful when mowing the lawn or trimming vegetation, activities that might arouse insects in a beehive or wasp nest.
• Have hives and nests near your home removed by a professional.

Know what to do when you’re exposed to bees:

• If a few bees are flying around you, stay calm and slowly walk away from the area. Swatting at an insect may cause it to sting.
• If a bee or wasp stings you, or many insects start to fly around, cover your mouth and nose and quickly leave the area. When a bee stings, it releases a chemical that attracts other bees. If you can, get into a building or closed vehicle.

Diagnosis of bee sting

If you’ve had a reaction to bee stings that suggests you might be allergic to bee venom, your doctor may suggest one or both of the following tests:

• Skin test. During skin testing, a small amount of allergen extract (in this case, bee venom) is injected into the skin of your arm or upper back. This test is safe and won’t cause any serious reactions. If you’re allergic to bee stings, you’ll develop a raised bump on your skin at the test site.
• Allergy blood test. A blood test can measure your immune system’s response to bee venom by measuring the amount of allergy-causing antibodies in your bloodstream. A blood sample is sent to a medical laboratory, where it can be tested for evidence of sensitivity to possible allergens.

Allergy skin tests and allergy blood tests are often used together to diagnose insect allergies. Your doctor may also want to test you for allergies to yellow jackets, hornets and wasps — which can cause allergic reactions similar to those of bee stings.

Treatment of bee sting

For ordinary bee stings that do not cause an allergic reaction, home treatment is enough. Multiple stings or an allergic reaction, on the other hand, can be a medical emergency that requires immediate treatment.

Emergency treatment for allergic reactions

• During an anaphylactic attack, an emergency medical team may perform cardiopulmonary resuscitation (CPR) if you stop breathing or your heart stops beating.

You may be given medications including:

• Epinephrine (adrenaline) to reduce your body’s allergic response
• Oxygen, to help you breathe
• Intravenous (IV) antihistamines and cortisone to reduce inflammation of your air passages and improve breathing
• A beta agonist (such as albuterol) to relieve breathing symptoms

Epinephrine autoinjector

If you’re allergic to bee stings, your doctor is likely to prescribe an emergency epinephrine autoinjector (EpiPen, Auvi-Q, others). You’ll need to have it with you at all times. An autoinjector is a combined syringe and concealed needle that injects a single dose of medication when pressed against your thigh. Always be sure to replace epinephrine by its expiration date.

Be sure you know how to use the autoinjector. Also, make sure the people closest to you know how to administer the drug — if they’re with you in an anaphylactic emergency, they could save your life. Medical personnel called in to respond to a severe anaphylactic reaction also may give you an epinephrine injection or another medication.

Consider wearing an alert bracelet that identifies your allergy to bee or other insect stings.

Allergy shots

Bee and other insect stings are a common cause of anaphylaxis. If you’ve had a serious reaction to a bee sting or multiple stings, your doctor likely will refer you to an allergist for allergy testing and consideration of allergy shots (immunotherapy). These shots, generally given regularly for a few years, can reduce or eliminate your allergic response to bee venom.

Home remedies for bee sting

If a bee stings you or your child, follow the suggestions below.

Treatment for minor reactions

• Remove the stinger as soon as you can, as it takes only seconds for all of the venom to enter your body. Get the stinger out any way you can, such as with your fingernails or a tweezer.
• Wash the sting area with soap and water.
• Apply a cold compress.

Treatment for moderate reactions

The following steps may help ease the swelling and itching often associated with large local reactions:

• Remove the stinger as soon as you can.
• Wash the affected area with soap and water.
• Apply a cold compress.
• Take an over-the-counter pain reliever as needed. You might try ibuprofen (Motrin IB, Children’s Motrin, others) to help ease discomfort.
• If the sting is on an arm or leg, elevate it.
• Apply hydrocortisone cream or calamine lotion to ease redness, itching or swelling.
• If itching or swelling is bothersome, take an oral antihistamine that contains diphenhydramine (Benadryl) or chlorpheniramine (Chlor-Trimeton).
• Avoid scratching the sting area. This will worsen itching and swelling and increase your risk of infection.

What is Anaphylaxis ?

Anaphylaxis is a life-threatening, systemic hypersensitivity reaction that may be caused by both immunological and nonimmunological mechanisms. Most reactions are immunoglobulin (IgE) mediated ². It is the most severe form of allergic reaction and is almost always unexpected ³. Delay in clinical diagnosis and treatment may result in death by airway obstruction or vascular collapse ². The incidence of anaphylaxis in the United States is 49.8 cases per 100,000 person-years ³. Lifetime prevalence is 0.05 to 2 percent, with a mortality rate of 1 percent ⁴. Compared with that of the general population, the risk of anaphylaxis is doubled in patients with mild asthma and tripled in those with severe disease ⁵. The true prevalence and mortality rates may be higher because of the unexpected nature of the disease, the lack of reliable confirmatory testing, confusion over the clinical definition, and underreporting by physicians ⁶. Patients may arrive at a physician’s office remote from an event or with active symptoms, or they may develop anaphylaxis after administration of common treatments used in the clinic. Patients need to be prepared to recognize and quickly treat anaphylaxis to prevent potentially catastrophic outcomes ⁷.

Triggers and Causes of Anaphylaxis

Anaphylaxis is a systemic response to a specific allergen, usually occurring within one hour of exposure. The most common triggers are food, insect stings, and medications (Table 1) ⁷. Food-related reactions are most common in children up to four years of age, and medication reactions are most common in patients older than 55 years ³.

Table 1. Possible Triggers of Anaphylaxis

Most cases of anaphylaxis are immunoglobulin E (IgE)–mediated. Antibodies exposed to a particular allergen attach to mast cells and basophils, resulting in their activation and degranulation. A variety of chemical mediators are released including histamine, heparin, tryptase, kallikrein, platelet-activating factor, bradykinin, tumor necrosis factor, nitrous oxide, and several types of interleukins ⁷, ⁶.

Historically, anaphylaxis-type reactions triggered by the direct activation of the mast cell (e.g., radiocontrast media reactions) were referred to as anaphylactoid reactions. Currently, immune and nonimmune anaphylaxis are the preferred terms to differentiate between IgE-mediated reactions and direct activation reactions. This distinction matters little in the acute clinical setting, because the treatment is the same for both types of reactions. However, the difference is important when deciding on prevention strategies, such as immunomodulation therapy ⁷, ⁶.

Signs and symptoms of anaphylaxis

Signs and symptoms usually develop within five to 30 minutes of exposure to the offending allergen, but may not develop for several hours. A biphasic reaction is a second acute anaphylactic reaction occurring hours after the first response and without further exposure to the allergen ⁸. One to 20 percent of patients with anaphylaxis experience biphasic reactions, which usually occur within eight hours of the initial reaction, but may occur as late as 24 to 72 hours after exposure ⁹.

Typical reactions with skin manifestations (urticaria) plus cardiovascular or respiratory involvement are easily diagnosed. However, some reactions are atypical and recognised only when the diagnosis is considered because of the context. A sudden onset of symptoms affecting two or more organ systems or just hypotension on its own, even without skin involvement, should trigger consideration of the diagnosis in the right context, ie. recent exposure to a potential allergen or stimulant. Hypotension may be absolute (systolic <90 mmHg) or relative – defined as a greater than 30% drop from baseline/normal for that patient ¹⁰.

Anaphylaxis must be considered as a possible cause in any case of acute respiratory distress, bronchospasm, hypotension and/or cardiac arrest. Some real-life examples of difficult to diagnose anaphylaxis are provided in Table 2. A common theme in these examples is the subtlety or absence of skin features. Some other pointers to consider are:

Table 2. Signs and symptoms of Anaphylaxis by Body System

In 2004, the Second Symposium on the Definition and Management of Anaphylaxis developed clinical criteria for diagnosing anaphylaxis in the acute setting (Table 3) ¹². The presence of one of three criteria predicts diagnosis of anaphylaxis 95 percent of the time ⁴. The clinical history is the most important tool to determine whether a patient has had an anaphylactic reaction and the cause of the episode ².

Table 3. Clinical Criteria for Diagnosing Anaphylaxis

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