What is black seed oil

Black seed (Nigella sativa) often called black cumin or black-caraway, also known as nigella or kalonji, is an annual flowering plant in the family Ranunculaceae, native to south and southwest Asia ¹. Nigella sativa plant can grow to 20-90 cm tall, with finely divided leaves, the leaf segments narrowly linear to threadlike. The flowers are delicate, and usually colored white, yellow, pink, pale blue or pale purple, with 5-10 petals. The fruit is a large and inflated capsule composed of 3-7 united follicles, each containing numerous seeds ².

Black seeds are used as a spice in Indian and Middle Eastern cuisines. The black seeds taste like a combination of onions, black pepper and oregano, depending on whom you ask ³. The seeds have a slightly bitter flavor and resemble cumin or oregano, depending on whom you ask. They have a pungent bitter taste and smell ⁴.

The dry-roasted black seeds flavor curries, vegetables and pulses. Black seed can be used as a “pepper” in recipes with pod fruit, vegetables, salads and poultry. In some cultures, the black seeds are used to flavor bread products. It is also used as part of the spice mixture panch phoron (meaning a mixture of five spices) and by itself in many recipes in Bengali cuisine and most recognizably in naan bread ³. Black seed is also used in Armenian string cheese, a braided string cheese called majdouleh or majdouli in the Middle East.

Black seeds reported to contain a fatty oil rich in unsaturated fatty acids, mainly linoleic acid (50-60%), oleic acid (20%), eicodadienoic acid (3%) and dihomolinoleic acid (10%) ⁵. Saturated fatty acids (palmitic, stearic acid) amount to about 30% or less. α-sitosterol is a major sterol, which accounts for 44% and 54% of the total sterols in Tunisian and Iranian varieties of black seed oils respectively, followed by stigmasterol (6.57-20.92% of total sterols) ⁶.

Black seeds contain both fixed and essential oils, proteins, alkaloids and saponin ⁷. Many active compounds have been isolated, identified and reported so far in different varieties of black seeds. The most important active compounds are thymoquinone (30%-48%), thymohydroquinone, dithymoquinone, p-cymene (7%-15%), carvacrol (6%-12%), 4-terpineol (2%-7%), t-anethol (1%-4%), sesquiterpene longifolene (1%-8%) α-pinene and thymol etc. Black seeds also contain some other compounds in trace amounts. Seeds contain two different types of alkaloids; i.e. isoquinoline alkaloids e.g. nigellicimine and nigellicimine-N-oxide, and pyrazol alkaloids or indazole ring bearing alkaloids which include nigellidine and nigellicine. Moreover, black seeds also contain alpha-hederin, a water soluble pentacyclic triterpene and saponin, a potential anticancer agent ⁸.

Some other compounds e.g. carvone, limonene, citronellol were also found in trace amounts. Most of the pharmacological properties of black seed are mainly attributed to quinine constituents, of which thymoquinone is the most abundant. On storage, thymoquinone yields dithymoquinone and higher oligocondensation products. Black seeds contain protein (26.7%), fat (28.5%), carbohydrates (24.9%), crude fibre (8.4%) and total ash (4.8 %). Black seeds are also containing good amount of various vitamins and minerals like Cu, P, Zn and Fe etc. The seeds contain carotene which is converted by the liver to vitamin A. Root and shoot are reported to contain vanillic acid ⁹.

Ghosheh et al. ¹⁰ described the quantification of four pharmacologically important components: thymoquinone, dithymoquinone, thymohydroquinone, and thymol, in the black seed oil by high performance liquid chromatography. Much of the biological activities of black seeds have been shown to be due to thymoquinone, the major component of the essential oil, which is also present in the fixed oil ⁷. Thymoquinone is considered as potent anti-oxidant ¹¹, anti-carcinogenic and anti-mutagenic agent ¹² (structure of thymoquinone is shown in Figure 1). Moreover, thymoquinone is a relatively safe compound, particularly when given orally to experimental animals ¹³. Alpha (α)-hederin, a pentacyclic triterpene saponin (structure: Figure 1b) isolated from the black cumin seeds of N. sativa, was also reported to have potent in vivo antitumor activity ¹⁴.

Many studies showed that black seed oil or thymoquinone has antioxidant activity and increases the activities of antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase etc ¹⁵. And antioxidant enzymes are clearly related to cancer- mostly their increased activities are beneficial against different types of cancer ¹⁶. Administration of black seed oil or thymoquinone can lower the toxicity of other anticancer drugs (for example, cyclophosphamide) by an up-regulation of antioxidant mechanisms, indicating a potential clinical application for these agents to minimize the toxic effects of treatment with anticancer drugs ¹⁷.

Figure 1. Thymoquinone and Alpha (α)-hederin chemical structure

Traditional uses of black seed in folk remedies

Black seed has been traditionally used for the treatment of a variety of disorders, diseases and conditions pertaining to respiratory system, digestive tract, kidney and liver function, cardio vascular system and immune system support, as well as for general well-being ¹⁸, ¹⁹.

Avicenna refers to black seeds in the “The Canon of Medicine”, as seeds stimulate the body’s energy and helps recovery from fatigue and dispiritedness. Black seeds and their oil have a long history of folklore usage in Indian and Arabian civilization as food and medicine ², ²⁰. The seeds have been traditionally used in Southeast Asian and the Middle East countries for the treatment of several diseases and ailments including asthma, bronchitis, rheumatism and related inflammatory diseases. Its many uses have earned Nigella the Arabic approbation ‘Habbatul barakah’, meaning the seed of blessing. A tincture prepared from the seeds is useful in indigestion, loss of appetite, diarrhoea, dropsy, amenorrhoea and dysmenorrhoea and in the treatment of worms and skin eruptions. Externally the oil is used as an antiseptic and local anesthetic. Roasted black seeds are given internally to stop the vomiting ²¹.

Black cumin seed oil benefits

Black seeds of Nigella sativa (family: Ranunculaceae), commonly known Black Cumin, or “Habbatul Barakah”, have long been used in folk medicine in the Arabian Gulf region, Far East Asia, and Europe ²².

In the traditional system of medicine practised in the Arabian Gulf region, Black Seed is recommended for a wide range of ailments, including fever, cough, bronchitis, asthma, chronic headache, migraine, dizziness, chest congestion, dysmenorrhea, obesity, diabetes, paralysis, hemiplagia, back pain, infection, inflammation, rheumatism, hypertension, and gastrointestinal problems such as dyspepsia, flatulence, dysentery, and diarrhea. It has been used as a stimulant, diuretic, emmenagogue, lactagogue, anthelmintic, and carminative ²³. Black Seed has also been used externally where it is applied directly to abscesses, nasal ulcers, orchitis, eczema, and swollen joints.

Many of the folk medicinal claims of Black Seed use have been scientifically tested ²². Over 150 studies have been conducted over the last five decades to investigate chemical and pharmacological properties of Black Seeds ²². Phytochemical studies of Black Seed showed the presence of >100 constituents. Many of these compounds have not been chemically identified nor have they been pharmacologically tested. A combination of fatty acids, volatile oils, and trace elements are believed to contribute to the pharmacological activity of Black Seeds ²².

This randomized, double blind clinical trial ²⁴ comparing the effect of black seed oil and fish oil in the treatment an autoimmune skin disease, vitiligo, where the body’s immune system destroy the melanocytes of the skin. The study found that skin application in 52 patients (40% female and 60% male of average age 45 years), the highest percentage of improvement in the black seed oil group was observed in the lower extremities, trunk, head, and neck; and in the fish oil group in the head and neck, trunk, and feet. The lowest percentage of improvement in the black seed oil group was observed in the head, neck, and hands; and in the fish oil group in the hands and lower extremities. No specific side effects were reported by patients during six months of treatment ²⁴. Both black seed oil and fish oil were effective in reduction the size of patient’s lesions (vitiligo) ²⁴. Most of the percent improvement observed in upper extremities, trunk, head, and neck of those who received black seed oil and head, neck, trunk, and feet for those who received fish oil.

The results of extensive pharmacological studies (in test tubes and on animal) on black seed and black seed oil found Black Seed have:

• Aanalgesic ²⁵,
• Antilipemic ²⁶, ²⁷,
• Postcoital contraceptive ²⁸,
• Diuretic and antihypertensive ²⁹,
• Bronchodilator and calcium antagonist ³⁰,
• Histamine release inhibitor ³¹, hepatoprotective ³²,
• Anthelmintic ³³,
• Antifungal ³⁴,
• Antimicrobial (against a wide range of organisms) ³⁵,
• Anticancer ³⁶,
• Diminishing the risk of atherosclerosis by decreasing the serum low density lipoprotein cholesterol level and increasing the serum high density lipoprotein cholesterol levels ³⁷,
• Exerts therapeutic and protective effect in diabetes by decreasing morphological changes and preserving pancreatic beta-cell integrity ³⁸ and by beneficially changing the hepatic enzyme activities ³⁹,
• Effective against hypertension ⁴⁰,
• Has a potent antihistaminic effect on airways of asthmatic patients ⁴¹,
• Its components are promising agents to complement schistosomiasis specific treatment ⁴²,
• Black seed oil protects kidney tissue against oxygen free radicals, preventing renal dysfunction and morphological abnormalities ⁴³ and
• Anti-inflammatory activities ⁴⁴.

Anticancer Activities of Black Seed (Black Cumin Seed)

Blood Cancer

El-Mahdy et al. ⁴⁵ reported that Thymoquinone exhibits anti-proliferative effect in human myeloblastic leukemia HL-60 cells. Derivatives of thymoquinone bearing terpene-terminated 6-alkyl residues were tested in HL-60 cells and 518A2 melanoma by Effenberger et al. ⁴⁶. They found the derivatives induce apoptosis associated with DNA laddering, a decrease in mitochondrial membrane potential and a slight increase in reactive oxygen species. Swamy and Huat ¹⁴ observed that α-hederin also induced death of murine leukemia P388 cells by a dose- and time-dependent increase in apoptosis.

Breast Cancer

Aqueous and alcohol extracts of black cumin seeds were found to be effective in vitro in inactivating MCF-7 breast cancer cells ⁴⁷. Black cumin seeds, in combination with melatonin and retinoic acid reduced the carcinogenic effects of DMBA (7, 12-di-methylbenz(a)anthracene) in mammary carcinoma of rats ⁴⁸. Terpene-terminated 6-alkyl residues of Thymoquinone were tested in MCF-7/Topo breast carcinoma by Effenberger et al. ⁴⁶. They found the derivatives inducing cell death by apoptosis.

Colon Cancer

Gali-Muhtasib et al. ⁴⁹ suggested that thymoquinone is anti-neoplastic and pro-apoptotic against colon cancer cell line HCT116. Salim and Fukushima ⁵⁰ demonstrated that the volatile oil of black seed has the ability to inhibit colon carcinogenesis of rats in the post-initiation stage, with no evident adverse side effects. Norwood et al. ⁵¹ suggested thymoquinone as chemotherapeutic agent on SW-626 colon cancer cells, in potency, which is similar to 5-flurouracil in action. However, on HT-29 (colon adenocarcinoma) cell, no effect of thymoquinone was found ⁵².

Pancreatic Cancer

Chehl et al. ⁵³ showed that thymoquinone, the major constituent of N. sativa oil extract, induced apoptosis and inhibited proliferation in PDA (pancreatic ductal adenocarcinoma) cells. They also suggested thymoquinone as a novel inhibitor of pro-inflammatory pathways, which provides a promising strategy that combines anti-inflammatory and proapoptotic modes of action. Thymoquinone also can abrogate gemcitabine- or oxaliplatin-induced activation of NF-kappa B, resulting in the chemosensitization of pancreatic tumors to conventional therapeutics ⁵⁴. The high molecular weight glycoprotein mucin 4 (MUC4) is aberrantly expressed in pancreatic cancer and contributes to the regulation of differentiation, proliferation, metastasis, and the chemoresistance of pancreatic cancer cells. Torres et al. ⁵⁵ evaluated the down-regulatory effect of thymoquinone on MUC4 in pancreatic cancer cells. But in a study, Rooney and Ryan ⁵² did not find any preventive role of thymoquinone on MIA PaCa-2 (pancreas carcinoma) cells.

Hepatic Cancer

The cytotoxic activity of N. sativa seed was tested on the human hepatoma HepG2 cell line by Thabrew et al. ⁵⁶, and 88% inhibitory effect on HepG2 was found after 24-hr incubation with different concentrations (0–50 mg/ml) of the N. sativa extract. Nagi and Almakki ⁵⁷ reported that oral administration of thymoquinone is effective in increasing the activities of quinone reductase and glutathione transferase and makes thymoquinone a promising prophylactic agent against chemical carcinogenesis and toxicity in hepatic cancer

Lung Cancer

Swamy and Huat ¹⁴ mentioned the antitumor activity of α-hederin from black cumin seed against LL/2 (Lewis Lung carcinoma) in BDF1 mice. Also, Mabrouk et al. ⁵⁸ showed that supplementation of diet with honey and N. sativa has a protective effect against MNU (methylnitrosourea)-induced oxidative stress, inflammatory response and carcinogenesis in lung, skin and colon. However, Rooney and Ryan ⁵² reported that α-hederin and thymoquinone, the two principal bioactive constituents of N. sativa enhance neither cytotoxicity nor apoptosis in A549 (lung carcinoma), HEp-2 (larynx epidermoid carcinoma) cells.

Skin cancer

Topical application of black cumin seed extract inhibited two-stage initiation/promotion [dimethylbenz[a]anthracene (DMBA)/croton oil] skin carcinogenesis in mice. Again, intraperitoneal administration of black cumin seed (100 mg/kg body wt) 30 days after subcutaneous administration of MCA (20-methylcholanthrene) restricted soft tissue sarcomas to 33.3% compared with 100% in MCA-treated controls ⁵⁹.

Fibrosarcoma

Thymoquinone from black cumin seed was administrated (0.01% in drinking water) one week before and after MCA treatment significantly inhibited the tumor incidence (fibrosarcoma) and tumor burden by 43% and 34%, respectively, compared with the results in the group receiving MCA alone. Moreover, Thymoquinone delayed the onset of MCA-induced fibrosarcoma tumors. Also in vitro studies showed that Thymoquinone inhibited the survival of fibrosarcoma cells with IC50 of 15 mM ⁶⁰. Black cumin seed oil also decreased the fibrinolytic potential of the human fibrosarcoma cell line (HT1080) in vitro ⁶¹.

Renal Cancer

Khan and Sultana ⁶² reported the chemo-preventive effect of black seed against ferric nitrilotriacetate (Fe-NTA)-induced renal oxidative stress, hyper-proliferative response and renal carcinogenesis. Treatment of rats orally with black cumin seed (50 100 mg/kg body wt) resulted in significant decrease in H2O2 generation, DNA synthesis and incidence of tumors.

Prostate Cancer

Thymoquinone, from black seed, inhibited DNA synthesis, proliferation, and viability of cancerous (LNCaP, C4-B, DU145, and PC-3) but not non-cancerous (BPH-1) prostate epithelial cells by down-regulating AR (androgen receptor) and E2F-1 (a transcription factor) ⁶³. In this study, they suggested thymoquinone as effective in treating hormone-sensitive as well as hormone-refractory prostate cancer. Yi et al. ⁶⁴ found that thymoquinone blocked angiogenesis in vitro and in vivo, prevented tumor angiogenesis in a xenograft human prostate cancer (PC3) model in mouse, and inhibited human prostate tumor growth at low dosage with almost no chemotoxic side effects. Furthermore, they observed that endothelial cells were more sensitive to thymoquinone-induced cell apoptosis, cell proliferation, and migration inhibition compared with PC3 cancer cells. Thymoquinone also inhibited vascular endothelial growth factor-induced extracellular signal-regulated kinase activation but showed no inhibitory effects on vascular endothelial growth factor receptor 2 activation.

Cervical Cancer

Shafi et al. ⁶⁵ reported that methanol, n-Hexane and chloroform extracts of black seed effectively killed HeLa (human epithelial cervical cancer) cells by inducing apoptosis. Effenberger et al. ⁴⁶ tested terpene-terminated 6-alkyl residues of thymoquinone on multidrug-resistant KB-V1/Vb1 cervical carcinoma and found the derivatives inducing cell death by apoptosis.

Black seed oil side effects

Many toxicological studies have been carried out on black seeds. It has been shown that no toxic effects were reported when black seed oil was given to mice via the stomach in an acute study. In a chronic toxicity study rats treated daily with an oral dose for 3 months caused no changes in key hepatic enzyme levels particularly aspartate-aminotransferase, alanine-aminotranferase, and gammaglutamyl-transferase ⁶⁶. Moreover, the histopathological results also showed to be normal for the tissues of heart, liver, kidneys and pancreas LD50 (LD 50 is a lethal dose, the amount of an ingested substance that kills 50 percent of a test sample. It is expressed in mg/kg, or milligrams of substance per kilogram of body weight) values of black seed oil of N. sativa obtained by single doses orally and intraperitoneally in mice, were reported to be 26.2-31.6 mg/kg and 1.86-2.26 mg/kg, respectively. The low toxicity of black seed oil, evidenced by high LD50 values, key hepatic enzyme stability and organ integrity, suggests a wide margin of safety for therapeutic doses of black seed oil ⁶⁷. In another study, the LD50 of thymoquinone was found to be 104.7 mg/kg (89.7-119.7) and 870.9 mg/kg (647.1-1 094.8) after intra-peritoneal injection and oral ingestion respectively. Whereas, LD50 in rats was found to be 57.5 mg/kg (45.6-69.4) and 794.3 mg/kg (469.8-1 118.8) after intra-peritoneal injection and oral ingestion respectively. The LD50 values presented here after intra-peritoneal injection and oral gavages are 10-15 times and 100-150 times greater than doses of thymoquinone reported for its anti-inflammatory, anti-oxidant and anti-cancer effects. These observations revealed that thymoquinone is a relatively safe compound, particularly when given orally to experimental animals ⁶⁸, ⁶⁹.

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52. Modes of action of alpha-hederin and thymoquinone, active constituents of Nigella sativa, against HEp-2 cancer cells. Rooney S, Ryan MF. Anticancer Res. 2005 Nov-Dec; 25(6B):4255-9. http://ar.iiarjournals.org/content/25/6B/4255.long[↩][↩][↩]
53. Anti-inflammatory effects of the Nigella sativa seed extract, thymoquinone, in pancreatic cancer cells. Chehl N, Chipitsyna G, Gong Q, Yeo CJ, Arafat HA. HPB (Oxford). 2009 Aug; 11(5):373-81. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2742606/[↩]
54. Antitumor activity of gemcitabine and oxaliplatin is augmented by thymoquinone in pancreatic cancer. Banerjee S, Kaseb AO, Wang Z, Kong D, Mohammad M, Padhye S, Sarkar FH, Mohammad RM. Cancer Res. 2009 Jul 1; 69(13):5575-83. http://cancerres.aacrjournals.org/content/69/13/5575.long[↩]
55. Effects of thymoquinone in the expression of mucin 4 in pancreatic cancer cells: implications for the development of novel cancer therapies. Torres MP, Ponnusamy MP, Chakraborty S, Smith LM, Das S, Arafat HA, Batra SK. Mol Cancer Ther. 2010 May; 9(5):1419-31. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2906253/[↩]
56. Cytotoxic effects of a decoction of Nigella sativa, Hemidesmus indicus and Smilax glabra on human hepatoma HepG2 cells. Thabrew MI, Mitry RR, Morsy MA, Hughes RD. Life Sci. 2005 Aug 5; 77(12):1319-30. https://www.ncbi.nlm.nih.gov/pubmed/15916774/[↩]
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58. Inhibition of methylnitrosourea (MNU) induced oxidative stress and carcinogenesis by orally administered bee honey and Nigella grains in Sprague Dawely rats. Mabrouk GM, Moselhy SS, Zohny SF, Ali EM, Helal TE, Amin AA, Khalifa AA. J Exp Clin Cancer Res. 2002 Sep; 21(3):341-6. https://www.ncbi.nlm.nih.gov/pubmed/12385575/[↩]
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61. In vitro decreases of the fibrinolytic potential of cultured human fibrosarcoma cell line, HT1080, by Nigella sativa oil. Awad EM. Phytomedicine. 2005 Jan; 12(1-2):100-7. https://www.ncbi.nlm.nih.gov/pubmed/15693715/[↩]
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63. Androgen receptor and E2F-1 targeted thymoquinone therapy for hormone-refractory prostate cancer. Kaseb AO, Chinnakannu K, Chen D, Sivanandam A, Tejwani S, Menon M, Dou QP, Reddy GP. Cancer Res. 2007 Aug 15; 67(16):7782-8. http://cancerres.aacrjournals.org/content/67/16/7782.long[↩]
64. Thymoquinone inhibits tumor angiogenesis and tumor growth through suppressing AKT and extracellular signal-regulated kinase signaling pathways. Yi T, Cho SG, Yi Z, Pang X, Rodriguez M, Wang Y, Sethi G, Aggarwal BB, Liu M. Mol Cancer Ther. 2008 Jul; 7(7):1789-96. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2587125/[↩]
65. Induction of apoptosis in HeLa cells by chloroform fraction of seed extracts of Nigella sativa. Shafi G, Munshi A, Hasan TN, Alshatwi AA, Jyothy A, Lei DK. Cancer Cell Int. 2009 Nov 27; 9():29. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2794855/[↩]
66. Ahmad A, Husain A, Mujeeb M, et al. A review on therapeutic potential of Nigella sativa: A miracle herb. Asian Pacific Journal of Tropical Biomedicine. 2013;3(5):337-352. doi:10.1016/S2221-1691(13)60075-1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3642442/[↩]
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What is black salve

Black salve was originally developed by an American surgeon, Jesse Fell, its use first reported in the 1850s ¹. Fell had heard of a plant growing on the shores of Lake Superior used by Native Americans to treat cancer ². He identified it as S. canadensis, combining it with zinc chloride to make a cancer salve known as Fells’ paste ³. Since then, other entrepreneurs have developed topical cancer therapies based on these two core ingredients, today’s formulations being known as black salve ⁴. However, the U.S. Food and Drug Administration has listed black salve as a “fake cancer cure” and warns consumers to avoid it ⁵, ⁶, ⁷.

Black salves usually contain bloodroot, the rhizome of Sanguinaria canadensis ⁸. Manufacturers have differing formulations that may also contain chaparral (Larrea mexicana), graviola (Annona muricata), oleander (Nerium oleander), galangal (Alpinia officinarum), ginger (Zingiber officinale), red clover (Trifolium pratense), sheep sorrel (Rumex acetosella), burdock (Arctium lappa), pokeroot (Phytolacca decandra), and turmeric (Curcuma longa) ⁸. Sanguinaria canadensis, also known as bloodroot, is a traditional medicine used by Native Americans to treat a diverse range of clinical conditions ². The rhizome of the plant, also known as bloodroot because of its red latex, contains a number of biologically active alkaloids and have been associated with clinical toxicities ranging from mouthwash induced leukoplakia to cancer salve necrosis and treatment failure ². The association of S. canadensis containing mouthwash with the development of leukoplakia and a murine model suggesting sanguinarine acts as a tumor promoter highlights the urgent need for studies into black salve carcinogenesis.

Apart from its botanical ingredients, black salve contains zinc chloride (ZnCl2) with some formulations also containing dimethyl sulfoxide (DMSO). ZnCl2 is a chemical usually manufactured from zinc and hydrochloric acid and does not occur naturally apart from the very rare mineral simonkolleite Zn5(OH)8Cl2H2O ⁹. Zinc chloride (ZnCl2) is widely used for industrial processes such as textile manufacture and metallurgical fluxes for soldering galvanized iron ¹⁰. The zinc chloride (ZnCl2) contained in black salve is a synthesized chemical and in some preparations the main ingredient by weight.

Dimethyl sulfoxide (DMSO) is added to enhance the epidermal penetration of some black salve formulations. Although trace amounts of dimethyl sulfoxide may be naturally found in cereals, fruits, and vegetables ¹¹, dimethyl sulfoxide (DMSO) is commercially manufactured from lignin, a byproduct of paper production ¹². DMSOs’ chemical synthesis utilizes lignins free methyl radicals; these are coupled to sulphur and then oxidized ¹³.

An increasing number of patients are turning to the Internet to provide them with information about healthcare and treatment options. As an unregulated space, there is the potential for inaccurate or misleading claims to result in choices leading to harmful health outcomes.

Patients seeking natural skin cancer therapies may not realize black salve contains significant quantities of synthetic chemicals. This knowledge may alter the treatment choices of complementary and alternative medicines patients, a population often wanting to reduce their exposure to unnatural compounds ¹⁴.

Conclusion

Black salve is not a natural therapy. It contains significant concentrations of synthetic chemicals. Black salve does not appear to possess tumour specificity with in vitro (test tubes) and in vivo (animal studies) evidence indicating normal cell toxicity ⁸. The use of black salve should be restricted to clinical research in low risk malignancies located at low risk sites until a better understanding of its efficacy and toxicity is developed. Clinicians should engage with patients and discourage black salve use, especially for high risk skin cancers and those in cosmetically sensitive areas ².

For topics on skin cancer please go here: Skin cancer

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What is argan oil

Argan oil is a plant oil produced from the kernels of the argan tree (Argania spinosa L.) that is endemic to Morocco. In Morocco, argan oil is used to dip bread in at breakfast or to drizzle on couscous or pasta. It is also used for cosmetic purposes. The argan fruit is oval-shaped and a little bigger than an olive. The outer layer of the argan nut is a thick peel that covers the fleshy part.

Argania spinosa is only endemic in south-western Morocco, where it covers an area of 3200 square miles that constitutes a unique biotope, named ‘the argan forest’. In Morocco, the argan forest has an essential agro-economic function. Because the argan tree is drought-resistant, it is also a powerful weapon for slowing down desertification ¹.

Traditionally, argan oil is exclusively prepared by women ². Once the ripe fruits have been collected, their peel and pulp are discarded, affording ovoid argan nuts of the size of a big olive. Argan nuts are then manually broken, the women firmly holding them between their thumb and index finger along the longest seed diagonal and violently hitting them with a stone. The kernels are then collected and roasted for a few minutes in clay plates if dietary argan oil is to be prepared. The roasted kernels are then crushed with a manual millstone, affording a brownish dough that is subsequently hand-mixed with warm water for several minutes. The wet dough is then hand-pressed, becomes solid and releases a brown emulsion that is decanted after several minutes to furnish the argan oil. The extraction residue (press cake) is very bitter, still rich in oil and used to feed cattle.

For industrial or laboratory purposes, argan oil can be extracted from pulverized kernels by lipophilic solvents ³. After solvent evaporation, argan oil is directly obtained. Only the cosmetics industry uses argan oil prepared according to this method. The term “enriched argan oil” describes an argan oil obtained by flash distillation of argan oil prepared by one of the above-mentioned methods ⁴. The level of unsaponifiable matter in this type of oil is three times lower than that observed in the press-extracted oil.

Figure 1. Argan fruit

Figure 2. Argan fruit

Argan oil nutrition facts

Argan oil does not contain essential omega-3, but the two main fatty acids found in argan oil are oleic acid (46–48 percent) and linoleic acid (omega 6 fatty acid) (31–35 percent), a mono- and a polyunsaturated fatty acid, respectively. The third and fourth main fatty acids found in argan oil are palmitic acid (11–14 percent) and stearic acid (4–7 percent) ⁵. These two latter acids are saturated fatty acids. From a nutritional point of view, these fatty acids are equivalent to peanut or sesame oils in terms of their lipid composition ⁶.

Unsaponifiable matter constitutes 1% of argan oil. It is made of carotenes (37%), tocopherols (8%), triterpene alcohols (20%), sterols (29%), and xanthophylls (5%). In extra-virgin argan oil, the levels of tocopherols are between 600 and 900 mg/kg. The main tocopherol found in argan oil is γ-tocopherol (between 81 and 92%) ⁷; it is a strong antioxidative agent. α-, β- and δ-tocopherols represent 2.4–6.5%, 0.1–0.3%, and 6.2–12.8%, respectively, of the total tocopherol fraction. Previous in vivo (animal studies) data indicate that γ-tocopherol may be a much more potent antioxidant than α-tocopherol. It is highly likely that γ-tocopherol unlike α-tocopherol will protect against reactive oxygen species mediated inflammation ⁸.

The sterol content of argan oils is in the range 272–357 mg/100g ⁹. These sterols are rare in vegetable oils, and interestingly, their occurrence in argan oil and the absence of β-sitosterol, which is present in several other vegetable oils is a bona fide marker of argan oil adulteration with other cheaper ones mostly containing β-sitosterol.

Other phenols have also been identified as traces using mass spectroscopy; they might also act as antioxidants. These phenol derivatives include caffeic acid, oleuropein, vanillic acid, tyrosol, ferulic acid, syringic acid, catechol, resorcinol, (–)-epicatechin, and (+)-catechin ¹⁰. Five ubiquitous triterpene alcohols have also been identified: tirucallol (27.9%), β-amyrine (27.3%), butyrospermol (18.1%), lupeol (7.1%), and 24-methylene cycloartanol (4.5%).

Table 1. Argan oil nutrition facts

Types of Argan oil

‘Cold-pressed oils’ and ‘virgin oils’ are two terms that can be confusing.

The term ‘cold-pressed oil’ can be used when a careful, gentle mechanical extraction of the raw material without application of heat is used. However, heat-treatment is allowed during preparation of the raw material and/or of the oil after the pressing process ¹².

Following this definition, edible argan oil is a cold-pressed oil. It is prepared by pressing the slightly roasted kernels of the argan tree [Argania spinosa (L.) Skeels] fruit.

Table 2. Differences between the four argan oil types

Traditional argan oil

This is the type of oil that has been prepared for centuries by Moroccan women on a family scale. However, traditionally prepared argan oil chemical composition is poorly reproducible. Such oil is generally of low quality and has a short shelf-life (Table 2). For a single person, 2–2.5 liter of oil are obtained from 100 kg of dry fruit after 58 h of work.

Cold-pressed argan oil

To produce large quantities of high-quality argan oil, women’s cooperatives have been started in south-western Morocco. In these cooperatives, argan oil is prepared by mechanically cold-pressing argan kernels. Using this technology, 4–6 liter of oil can be obtained from 100 kg of dry fruit after 13 hours of work by a single person.

Edible argan oil is prepared from roasted kernels, whereas unroasted kernels are used in the production of cosmetic argan oil (Table 2). The origin of the fruit and the processing method used dramatically influence the quality of the argan oil produced. Because of this, stringent preparation rules have been implemented in the cooperatives. These include the use of mechanical pressing in place of hand-pressing and mechanical fruit peeling. The polyphenol and tocopherol content of traditionally extracted and cold-pressed argan oils is similar. Their different shelf life is mainly due to the selection of the argan nuts and the frequent use of water of poor bacteriological quality during the traditional process.

Edible argan oil is also the major constituent of ‘Amlou’, a highly nutritive preparation whose composition also includes large quantities of crushed almonds and honey.

Cosmetic argan oil is directly used for skin application or as a hair lotion. It does not have the hazelnut taste of edible argan oil. Its content of volatile components is lower than that of edible argan oil ¹³ and its shelf life is also shorter, the latter extending up to 2 years, probably due to the formation during roasting of Maillard compounds, which favour preservation ¹⁴.

Solvent-extracted argan oil

Industrially, cosmetic argan oil is prepared by solvent extraction of crushed argan kernels. No quality control is required for argan nuts (Table 2). Solvent-extracted argan oil, which is also sometimes flash distilled and deodorised, is used exclusively in the composition of creams, shampoos and body lotions. Preservatives are frequently added to compensate for the naturally protective agents lost during extraction and/or distillation (tocopherols, polyphenols etc.).

Argan oil benefits

Argan oil has been used as a food and as a food ingredient, and has been applied to the skin for centuries, therefore its acute and chronic toxicity is assumed to be nil, particularly when orally administered at ordinary doses. Initially, argan oil’s pharmacological properties have simply been deduced by consideration of the properties of its constituents, which have been isolated and pharmacologically evaluated, often in simple models. The chemical composition of argan oil has already been reviewed in detail ¹⁵. Recently, scientific evaluation of the traditionally claimed benefits of argan oil consumption has begun, using animal models or cohort or clinical studies. These studies (Table 3) were aimed at determining if argan oil has only nutritional properties or if it can be said to also possess pharmacological properties ¹⁶. Nevertheless, the general benefits indicated by some primary results have already triggered the preparation of argan oil-based emulsions for parenteral nutrition ¹⁷.

Table 3. Key papers on the pharmacology of argan oil and their scientific findings

Cancer chemoprotective effects

Because argan and olive oils share a similar composition, the cancer chemoprotective effect attributed to olive oil has also been attributed to argan oil ¹⁸. Argan oil’s high levels of γ-tocopherol – by far the most potent antioxidant of the tocopherols – and its high squalene content have even led to a suggestion that its chemoprotective effect may even be greater ³⁶.

Prevention of obesity and adverse cardiovascular outcomes

Hypercholesterolemia and platelet hyperactivity are associated with an increased risk of adverse cardiovascular outcomes (coronary artery disease, hypertension etc.). Phenolic compounds, phytosterols and tocopherols are well known as efficient hypocholesterolemic agents. Not surprisingly, argan oil’s phenolic fraction prevents low-density lipoprotein (LDL “bad” cholesterol) oxidation in isolated human plasma ³⁷. Phenolic compounds also enhance reverse cholesterol transport by increasing high-density lipoprotein (HDL “good” cholesterol) lipid-bilayer fluidity ³⁷. The presence of these derivatives is therefore commonly used to explain the anti-atherogenic potential of argan oil ³⁷.

Antidiabetic activity

The cardiovascular protective and antidiabetic effects of argan oil are the most longstanding claimed pharmacological effects of argan oil ¹. So far, however, the only scientific demonstration of a possible antidiabetic activity has been in rats ³¹. Oral glucose test tolerance was performed on healthy or streptozotocin-induced diabetic rats. Oral glucose test tolerance was performed on healthy or streptozotocin-induced diabetic rats. Intraperitoneal administration of argan oil (2.5 ml/kg) 30 min before oral glucose loading (1 g/kg) induced a significant glycemia reduction that lasted for 3 h.[60] Argan oil also significantly reduced the amount of absorbed glucose in perfused jejunum segment ³¹. Samane et al. compared the metabolic response of rats to a free-access high-fat/high-sucrose diet in which 6% of the fat was replaced either by argan oil or fish oil. Intake of argan and fish oil resulted in the restoration of insulin signalling in fat and liver but fish oil also restored systemic insulin sensitivity ³⁸.

Other potential yet to be proven health benefits of argan oil

Some few clinical studies provide evidence that argan oil can promote additional benefits on risk factors for cardiovascular disease. In 2005, sixty young men were included in an interventional study. The analysis of the data indicated an increase of paraoxanase 1 (PON1) activities coupled with an increase of plasma vitamin E concentration ³⁹. Some years later, the vitamin E serum level of 151 menopausal women consuming either olive or argan oil was determined, and in the argan oil consumer group, Vitamin E serum level was increased ⁴⁰. In another study carried out on 60 young and healthy male volunteers aged between 23 and 40 years old, consumption of argan oil showed, after three weeks of intake, a significant increase in serum concentration levels of the androgen hormones including testosterone and luteinizing hormone ⁴¹. More recently, 37 patients (18 men, 19 women) with end-stage renal disease on maintenance displayed an improvement in markers directly associated with the lipid profile and oxidative stress status ⁴². In addition, evidence from sixty menopausal women indicates that the daily consumption and/or topical application of argan oil for a period of 1–2 months has an anti-aging effect on the skin demonstrated by the improvement of skin elasticity ⁴³.

As regards to argan pulp, this is described to contain essential oils and an unsaponifiable fraction (up to 3.3%) which is rich in sterols and tritepene aglycones. Some compounds have already found industrial applications such as erythrodiol ⁴⁴. Glycosylated triterpenes (saponins) of the basic acid-type in the argan pulp have been assayed in a few preliminary biological assays and deserve special attention related to their pharmacology. These are more particularly fungicidal against Cladosporium cucumerinum and Polysticus versicolor, antibacterial as well as analgesic and anti-inflammatory agents with low toxicity. Molluscicidal activity against Biophalaria glabrata, has also been reported ⁴⁵. Argan pulp, contains a diverse range of polyphenols with flavans, procyanidins, flavonoids (mostly quercetin derivatives), phenolic acids along with a minor phenolic aldehyde being reported at a concentration of up to 15.4 g/kg ⁴⁶. The acyl-glucosylflavonoids which are also present in argan pulp have shown a variety of functions, such as anti-feedant and phytoalexin capacity, signaling molecules, and UV protectants ⁴⁷. Acyl-glucosylpolyphenols are physiologically important phenolic compounds in plants because these are the final, functional products of secondary metabolism ⁴⁸.

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What is activated charcoal

Activated charcoal also called activated carbon, is a form of carbon processed to have small, low-volume pores that increase the surface area available for adsorption or chemical reactions. Activated charcoal main uses are in air purification, decaffeination, gold purification, metal extraction, water purification, medicine, sewage treatment, air filters in gas masks and respirators, filters in compressed air and many other applications. One major industrial application involves use of activated charcoal in the metal finishing field. It is very widely employed for purification of electroplating solutions. For example, it is a main purification technique for removing organic impurities from bright nickel plating solutions. A variety of organic chemicals are added to plating solutions for improving their deposit qualities and for enhancing properties like brightness, smoothness, ductility, etc. Due to passage of direct current and electrolytic reactions of anodic oxidation and cathodic reduction, organic additives generate unwanted breakdown products in solution. Their excessive build up can adversely affect the plating quality and physical properties of deposited metal. Activated charcoal treatment removes such impurities and restores plating performance to the desired level.

Activated charcoal is also used in the emergency treatment of certain kinds of poisoning and overdoses following oral ingestion. Activated charcoal tablets and capsules are also used in many countries as an over-the-counter drug to treat diarrhea, indigestion, and flatulence, even though there is insufficient evidence of the benefits and efficacy for these applications.

Activated charcoal helps prevent the poison from being absorbed from the stomach into the body ¹. Sometimes, several doses of activated charcoal are needed to treat severe poisoning. Activated charcoal is good at trapping chemicals and prevents their absorption. However, based on volunteer studies by the American Academy of Clinical Toxicology and European Association of Poisons Centres and Clinical Toxicologists ², single-dose activated charcoal should not be administered routinely in the management of poisoned patients. In volunteer studies, using at least 50 g of activated charcoal, demonstrated that the effectiveness of activated charcoal decreases with time. Data showed a mean reduction in absorption of 47.3%, 40.07%, 16.5% and 21.13%, when activated charcoal was administered at 30 minutes, 60 minutes, 120 minutes and 180 minutes, respectively, after dosing. Furthermore, the poison must be known to be adsorbed to charcoal and must have been swallowed under one hour previously. Furthermore, activated charcoal should not be administered unless a patient has an intact or protected airway.

Ordinarily, this medicine is not effective and should not be used in poisoning if corrosive agents such as alkalis (lye) and strong acids, iron, boric acid, lithium, petroleum products (e.g., cleaning fluid, coal oil, fuel oil, gasoline, kerosene, paint thinner), or alcohols have been swallowed, since it will not prevent these poisons from being absorbed into the body ¹.

Some activated charcoal products contain sorbitol. Sorbitol is a sweetener. It also works as a laxative, for the elimination of the poison from the body.Products that contain sorbitol should be given only under the direct supervision of a doctor because severe diarrhea and vomiting may result.

Activated charcoal has not been shown to be effective in relieving diarrhea and intestinal gas ¹.

Activated charcoal may be available without a doctor’s prescription; however, before using activated charcoal, call a poison control center, your doctor, or an emergency room for advice.

This product is available in the following dosage forms:

• Liquid
• Suspension
• Tablet
• Tablet, Chewable
• Kit
• Powder for Suspension.

An adequate airway assessment must take place before administration of activated charcoal. In patients with a depressed level of consciousness, doctors must consider the risk-to-benefit ratio of intubation for airway protection and the therapeutic benefits of activated charcoal.

Aspiration pneumonitis can occur after vomiting in patients with a depressed level of consciousness and in those who are fully alert with intact airway reflexes. Aspiration from vomit and misplaced nasogastric tubes for activated charcoal administration have led to severe respiratory compromise and even death.

Vomiting occurs more often when activated charcoal is administered rapidly. The risk of vomiting increases when sorbitol is added to activated charcoal.

Patients should be monitored for mental status changes and continued protection of their airway if vomiting occurs. Your doctor should perform serial abdominal examinations to evaluate for signs of obstruction, or peritonitis, especially if multiple-dose activated charcoal is given.

Activated charcoal has listed drug interactions for leflunomide and teriflunomide as risk category D (consideration of therapy modification) due to decreased systemic absorption of these drugs.

No significant toxicity from activated charcoal exists as it is not systemically absorbed, however, adverse effects from the administration as listed above such as emesis, aspiration, and bowel obstruction requiring manual, or surgical decompression can occur.

How to activated charcoal is made

Common charcoal is made from peat, coal, wood, coconut shell, or petroleum. “Activated charcoal” is similar to common charcoal, but is made especially for use as a medicine. To make activated charcoal, manufacturers heat common charcoal in the presence of a gas that causes the charcoal to develop lots of internal spaces or “pores.” These pores help activated charcoal “trap” chemicals.

What does activated charcoal do?

Activated charcoal adsorbs xenobiotics (synthetic chemicals) within the gastrointestinal tract due to hydrogen bonding, ion-ion forces, and van der Waals forces ³. The activated charcoal/xenobiotic complex prevents systemic absorption of that xenobiotic. Activated charcoal only adsorbs xenobiotics that are in the dissolved liquid phase via direct contact. Orally administered activated charcoal is not absorbed through the gastrointestinal lumen and acts within the gastrointestinal (GI) tract in its unchanged form.

Xenobiotics (synthetic chemicals) come in contact with activated charcoal if the drug has not yet been absorbed from the gastrointestinal lumen, or via recirculation of the xenobiotic into the gut lumen by either enterohepatic recirculation, or entero-enteric recirculation through active secretion, or passive diffusion.

Activated charcoal adsorption of xenobiotics is based on the equilibrium between the free xenobiotic and the activated charcoal/xenobiotic complex. Desorption of the xenobiotic from activated charcoal may occur. However, in the presence of adequate doses of activated charcoal, the equilibrium is shifted towards the activated charcoal/xenobiotic complex. This attempt to shift the equilibrium in favor of activated charcoal/xenobiotic complexes is the rationale for dosing activated charcoal to an activated charcoal: the xenobiotic ratio of 10:1.

Activated charcoal best adsorbs xenobiotics in their nonionized forms. Polar, water-soluble molecules are less likely to be adsorbed. Due to the pharmacodynamics of activated charcoal, nonpolar, poorly water-soluble organic xenobiotics are best absorbed.

Most xenobiotics will have decreased systemic absorption in the presence of activated charcoal, including acetaminophen, aspirin, barbiturates, tricyclic antidepressants, theophylline, phenytoin, and a majority of inorganic and organic materials. It is important to note that activated charcoal does not effectively adsorb alcohols, metals such as iron and lithium, electrolytes such as magnesium, potassium, or sodium, and acids or alkalis due to the polarity of these substances.

Before Using Activated Charcoal

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to medicines in this group or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Activated charcoal should be used only under the direct supervision of your doctor, poison control center, or other health care professional ⁴.

Geriatric

Many medicines have not been studied specifically in older people. Therefore, it may not be known whether they work exactly the same way they do in younger adults. Although there is no specific information comparing the use of activated charcoal in the elderly, this medicine is not expected to cause different side effects or problems in older people than it does in younger adults.

However, elderly persons with slow digestion are more likely to develop constipation if given more than one dose of activated charcoal.

Pregnancy

Activated charcoal has not been reported to cause birth defects or other problems in humans.

Breastfeeding

Activated charcoal has not been reported to cause problems in nursing babies.

Drug Interactions

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking any of these medicines, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Activated charcoal absorbs substances in the stomach and intestines. Taking activated charcoal along with medications taken by mouth can decrease how much medicine your body absorbs, and decrease the effectiveness of your medication. To prevent this interaction, take activated charcoal at least one hour after medications you take by mouth.

Using medicines in this class with any of the following medicines is not recommended. Your doctor may decide not to treat you with a medication in this class or change some of the other medicines you take.

• Naltrexone

Using medicines in this class with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Bromazepam
• Bromopride
• Buprenorphine
• Bupropion
• Butorphanol
• Carbinoxamine
• Codeine
• Digoxin
• Dihydrocodeine
• Donepezil
• Doxylamine
• Fentanyl
• Flibanserin
• Hydrocodone
• Lorazepam
• Meclizine
• Meperidine
• Methadone
• Morphine
• Morphine Sulfate Liposome
• Mycophenolate Mofetil
• Mycophenolic Acid
• Oxycodone
• Oxymorphone
• Pentazocine
• Periciazine
• Remifentanil
• Sufentanil
• Tapentadol
• Tiotropium
• Tramadol
• Zolpidem

Other Interactions

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Alcohol (Ethanol)

Alcohol may make activated charcoal less effective in “trapping” poisons and other chemicals.

Activated charcoal is sometimes used to prevent poisons from being absorbed into the body. Taking alcohol with activated charcoal might decrease how well activated charcoal works to prevent poison absorption.

Syrup of ipecac

Activated charcoal can bind up syrup of ipecac in the stomach. This decreases the effectiveness of syrup of ipecac.

Other Medical Problems

The presence of other medical problems may affect the use of medicines in this class. Make sure you tell your doctor if you have any other medical problems, especially:

• Bleeding, intestinal or
• Blockage, intestinal or
• Hole in the intestine—Activated charcoal may make these conditions worse.

Don’t use activated charcoal if you have any kind of intestinal obstruction !

Also, if you have a condition that slows the passage of food through your intestine (reduced peristalsis), don’t use activated charcoal, unless you are being monitored by your healthcare provider.

Decreased alertness—To prevent activated charcoal from getting into the patient’s lungs, it may be necessary to place a tube in the patient’s throat before activated charcoal is given.

Dehydration—Use of laxatives, such as sorbitol, is not recommended.

Slow digestion—Activated charcoal may not work properly.

Surgery, recent—Activated charcoal may cause abdominal or stomach problems.

Activated charcoal contraindications

A position statement from the American Academy of Clinical Toxicology (AACT) in 2005 lists the following as contraindications and relative contraindications for activated charcoal use:

• Patients with an unprotected airway (in other words, a depressed level of consciousness) without endotracheal intubation
• If activated charcoal use is likely to increase the risk and severity of aspiration of a xenobiotic (hydrocarbons with high aspiration potentials)
• When the risk of gastrointestinal perforation or hemorrhage is high secondary to medical conditions or recent surgery
• When endoscopy is likely to be attempted as activated charcoal may obscure endoscopic visualization
• In the presence of an intestinal obstruction
• When activated charcoal is known to not meaningfully adsorb the ingested xenobiotic such as metals, acids, alkalis, electrolytes, or alcohols

Multiple-dose activated charcoal (MDAC) is relatively contraindicated if decreased peristalsis is likely to occur from the substance ingested (opioids or anticholinergics). If multiple-dose activated charcoal (MDAC) is given to these patients, they should be monitored closely for development of obstruction, or potential aspiration.

Activated charcoal uses

An oral suspension of activated charcoal should be considered in poisonings when gastrointestinal decontamination of a synthetic chemical that is foreign to the body is indicated, and activated charcoal can be administered within 1 hour of ingestion ³. Careful consideration of the contraindications (see above) should occur prior to treatment with activated charcoal ⁵.

Activated charcoal is used to ⁶:

• treat poisonings,
• reduce intestinal gas (flatulence),
• lower cholesterol levels,
• prevent hangover, and
• treat bile flow problems (cholestasis) during pregnancy.

Before taking this medicine, call a poison control center, your doctor, or an emergency room for advice. It is a good idea to have these telephone numbers readily available.

Observational trial data in recent years suggests activated charcoal should be given and may substantially reduce drug absorption and bioavailability in the following circumstances:

• In anticipation of serious toxicity
• Recent toxic ingestions. While the timeframe of less than 1 hour is classically described, activated charcoal administration may be beneficial if administered up to 4 hours after large ingestions and for the ingestion of substances with anticholinergic, or opioid properties that decrease intestinal motility
• In alert and cooperative patients
• When airway reflexes are intact, or the airway is protected by an endotracheal tube
• Ingestions of xenobiotics without specific antidotes
• When the ability to administer activated charcoal at activated charcoal: drug ratios is greater than 40:1. While an activated charcoal: drug ratio of 10:1 was previously thought to be ideal, recent studies suggest a ratio of 40:1 may be more beneficial. This ratio may be difficult to achieve in ingestions of a large drug mass at initial doses of activated charcoal are typically 25 to 100 g, and the risk of emesis increases as the amount of activated charcoal administered increases.
• Ingestion of delayed release drugs. Single-dose activated charcoal may be efficacious outside of a 1-hour time frame when the systemic absorption of modified release substances is delayed.

Activated charcoal can be given for substances known to be adsorbed by activated charcoal.

Multi-dose activated charcoal is often considered in cases of life-threatening ingestions of carbamazepine, dapsone, phenobarbital, quinine, and theophylline. Additional indications for possible multi-dose activated charcoal therapy are listed below.

To prevent activated charcoal powder from scattering, be careful when opening and adding water to the powder container.

It is very important that you shake the liquid form of this medicine well before taking it, because some might have settled in the bottom. Be sure to drink all the liquid. Then rinse the container with a small amount of water, shake the container, and drink this mixture to get the full dose of activated charcoal.

If you have been told to take both this medicine and ipecac syrup to treat the poisoning, do not take this medicine until after you have taken the ipecac syrup to cause vomiting and the vomiting has stopped. This usually takes about 30 minutes.

Do not take this medicine mixed with chocolate syrup, ice cream or sherbet, since they may prevent the medicine from working properly.

If you are taking any other medicine, do not take it within 2 hours of the activated charcoal. Taking other medicines together with activated charcoal may prevent the other medicine from being absorbed by your body. If you have any questions about this, check with your health care professional.

Activated charcoal by other names

Activated Carbon, Animal Charcoal, Carbo Vegetabilis, Carbon, Carbón Activado, Charbon Actif, Charbon Activé, Charbon Animal, Charbon Médicinal, Charbon Végétal, Charbon Végétal Activé, Charcoal, Gas Black, Lamp Black, Medicinal Charcoal, Noir de Gaz, Noir de Lampe, Vegetable Carbon, Vegetable Charcoal.

US Brand Name

• Actidose-Aqua
• Charcoal
• Diarrest
• Di-Gon II
• Donnagel
• EZ-Char
• Kaodene NN
• Kaolinpec
• Kaopectate
• Kaopek
• Kerr Insta-Char

Canadian Brand Name

• Aqueous Charcodote Adult
• Aqueous Charcodote Pediatric
• Charcodote
• Charcodote Pediatric
• Charcodote Tfs
• Charcodote Tfs Pediatric
• Donnagel-Mb
• Kao-Con
• Parepectolin.

How effective is activated charcoal

Likely effective for:

• Trapping chemicals to stop some types of poisoning when used as a part of standard treatment.

Insufficient evidence to rate effectiveness for:

• Lowering cholesterol levels. So far, research studies don’t agree about the effectiveness of taking activated charcoal by mouth to lower cholesterol levels in the blood.
• Decreasing gas (flatulence). Some studies show that activated charcoal is effective in reducing intestinal gas, but other studies don’t agree. It’s too early to come to a conclusion on this.
• Treating reduced bile flow (cholestasis) during pregnancy. Taking activated charcoal by mouth seems to help treat cholestasis in pregnancy, according to some early research reports.
• Preventing hangover. Activated charcoal is included in some hangover remedies, but some experts are skeptical about how well it might work. Activated charcoal doesn’t seem to trap alcohol well.
• Other conditions.

More evidence is needed to rate the effectiveness of activated charcoal for these uses.

Activated charcoal dosage

Activated charcoal should be administered when a synthetic chemical is believed to still be in the gastrointestinal tract and when the benefits of preventing absorption of the synthetic chemical are assumed to outweigh the risks of activated charcoal. Optimal dosing of activated charcoal is unknown. activated charcoal can be administered orally, or via nasogastric and orogastric tubes. When the dose of the synthetic chemical is known, experts recommend activated charcoal at a 10:1 ratio of activated charcoal:xenobiotic. This may be impractical to achieve a 10:1 ratio when large doses (APAP or salicylates) are ingested. When the amount of xenobiotic ingested is unknown, or it is impractical to achieve a 10:1 ratio in large dose xenobiotic ingestions, single-dose activated charcoal should be administered in doses of 1g/kg of body weight.

Single-dose activated charcoal can either be given as a 1 g/kg of body weight dose, or simplified age-based dosing below:

• Single-dose activated charcoal dosing adult: 25 to 100 g
• Single-dose activated charcoal dosing infants younger than 1 year: 10 to 25 g
• Single-dose activated charcoal children 2 to 12 years: 25 to 50 g
• Single-dose activated charcoal children older than 12 years: follow adult dosing

Multiple-dose activated charcoal is used when at least 2 sequential doses, and often several more, of activated charcoal, are given. multi-dose activated charcoal is believed to prevent ongoing absorption of drug remaining within the GI tract and enhance elimination via enterohepatic or entero-enteric recirculation. While the quality of clinical data is not robust, multi-dose activated charcoal is believed to be beneficial for “potentially life-threatening” ingestions of the following substances: carbamazepine, dapsone, phenobarbital, quinidine, theophylline, amitriptyline, dextropropoxyphene, digitoxin, digoxin, disopyramide, nadolol, phenylbutazone, phenytoin piroxicam, sotalol, amiodarone, dosulepin, duloxetine, lamotrigine, valproic acid, and verapamil.

Dosing strategies of multi-dose activated charcoal vary. An initial dose of 10:1 ratio of activated charcoal: xenobiotic or 1 g/kg of bodyweight activated charcoal can be administered. It is best to tailor the dose and dosing intervals of multi-dose activated charcoal to the amount and dosage form of xenobiotic ingested. Interval multi-dose activated charcoal doses range from 0.25 to 0.5 g/kg of body weight every 1 to 6 hours in adults. activated charcoal has also been continuously administered through an nasogastric tube in some cases.

A simplified multi-dose activated charcoal approach for adult patients would be:

• Loading dose of 25 to 100 g
• Repeat doses of 10 to 25 g activated charcoal every 2 to 4 hours

Due to the variability in proper dosing strategies and indications for multi-dose activated charcoal administration, it would be a reasonable approach to consult a regional toxicologist, or Poison Control Center before the initiation of multi-dose activated charcoal therapy.

Formulations have been attempted to increase the palatability of activated charcoal which comes in a black color and has a gritty texture. Ready-to-use aqueous suspensions of activated charcoal are available in 15 g, 25 g, and 50 g doses as well as formulations premixed with sorbitol. If activated charcoal is not premixed, a slurry can be made with activated charcoal in a 1:8 ratio of activated charcoal to a suitable liquid such as water, cola, or flavored syrups. Offering activated charcoal in an opaque cup with a lid and straw is an easy way to increase the palatability of activated charcoal.

Dosing

The dose medicines in this class will be different for different patients. Follow your doctor’s orders or the directions on the label. The following information includes only the average doses of these medicines. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

For activated charcoal

• —For oral dosage form (powder):
  • For treatment of poisoning:
    • Treatment with one dose:
      • Adults and teenagers—Dose is usually 25 to 100 grams mixed with water.
      • Children 1 through 12 years of age—Dose is usually 25 to 50 grams mixed with water, or the dose may be based on body weight. It may be 0.5 to 1 gram per kilogram (kg) (0.23 to 0.45 gram per pound) of body weight mixed with water.
      • Children up to 1 year of age—Dose is usually 10 to 25 grams mixed with water, or the dose may be based on body weight. It may be 0.5 to 1 gram per kg (0.23 to 0.45 gram per pound) of body weight mixed with water.
    • Treatment with more than one dose:
      • Adults and teenagers—At first, the dose is 50 to 100 grams. Then the dose may be 12.5 grams given every hour, 25 grams given every two hours, or 50 grams given every four hours. Each dose should be mixed with water.
      • Children up to 13 years of age—At first, the dose is 10 to 25 grams. Then the dose is based on body weight. It is usually 1 to 2 grams per kg (0.45 to 0.91 gram per pound) of body weight given every two to four hours. Each dose should be mixed with water.
• —For oral dosage form (oral suspension):
  • For treatment of poisoning:
    • Treatment with one dose:
      • Adults and teenagers—Dose is usually 25 to 100 grams.
      • Children 1 through 12 years of age—Dose is usually 25 to 50 grams, or the dose may be based on body weight. It may be 0.5 to 1 gram per kg (0.23 to 0.45 gram per pound) of body weight.
      • Children up to 1 year of age—Dose is usually 10 to 25 grams, or the dose may be based on body weight. It may be 0.5 to 1 gram per kg (0.23 to 0.45 gram per pound) of body weight.
    • Treatment with more than one dose:
      • Adults and teenagers—At first, the dose is 50 to 100 grams. Then the dose may be 12.5 grams given every hour, 25 grams given every two hours, or 50 grams given every four hours.
      • Children up to 13 years of age—At first, the dose is 10 to 25 grams. Then the dose is based on body weight. It is usually 1 to 2 grams per kg (0.45 to 0.91 gram per pound) of body weight given every two to four hours.

For activated charcoal and sorbitol

• For oral dosage form (oral suspension):
  • For treatment of poisoning:
    • Adults and teenagers—Dose is usually 50 to 100 grams of activated charcoal given one time.
    • Children 1 through 12 years of age—Dose is usually 25 to 50 grams of activated charcoal given one time.
    • Children up to 1 year of age—Use is not recommended.

Storage

Keep out of the reach of children.

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Do not keep outdated medicine or medicine no longer needed.

Activated charcoal side effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Activated charcoal is safe for most adults when used short-term. Side effects of activated charcoal include constipation and black stools. More serious, but rare, side effects are a slowing or blockage of the intestinal tract, regurgitation into the lungs, and dehydration.

Check with your doctor as soon as possible if any of the following side effects occur:

Less common or rare

• Pain or swelling in stomach

Other side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. However, check with your doctor if any of the following side effects continue:

More common

• Diarrhea

Less common or rare

• Constipation
• vomiting

Activated charcoal will cause your stools to turn black. This is to be expected while you are taking this medicine.

There have not been any other side effects reported with this medicine. However, if you notice any other effects, check with your doctor.

Activated charcoal paste/powder for teeth

Due to recent online marketer promoting the sale of activated charcoal gel and powder for dental uses, Brooks et al conducted a review ⁷ that appeared in the Journal of the American Dental Association. The authors search for clinical studies on the use of charcoal and charcoal-based dentifrices and laboratory investigations on the bioactivity or toxicity of charcoal and charcoal-based dentifrices. What they found was insufficient clinical and laboratory data to substantiate the safety and efficacy claims of charcoal and charcoal-based dentifrices ⁷. They also cautioned dental clinicians about advising their patients to be cautious when using charcoal and charcoal-based dentifrices with unproven claims of efficacy and safety.

Their last message was “caveat emptor”, which means “let the buyer beware”, particularly when dealing with unproven (safety and benefits) dental products e.g. charcoal toothpaste, charcoal chewing gum.

If you are interested to whiten your teeth and want a product that work see our other post on teeth whitening here: How to Whiten Teeth Naturally

1. Charcoal, Activated (Oral Route). Mayo Clinic. https://www.mayoclinic.org/drugs-supplements/charcoal-activated-oral-route/description/drg-20070087[↩][↩][↩]
2. Position Paper: Single-Dose Activated Charcoal. American Academy of Clinical Toxicology & European Association of Poisons Centres and Clinical Toxicologists. Clinical Toxicology Vol. 43, Iss.2,2005. http://www.tandfonline.com/doi/full/10.1081/CLT-51867[↩]
3. Silberman J, Taylor A. Activated Charcoal. [Updated 2018 Nov 22]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2019 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482294[↩][↩]
4. Charcoal, Activated (Oral Route). Mayo Clinic. https://www.mayoclinic.org/drugs-supplements/charcoal-activated-oral-route/before-using/drg-20070087[↩]
5. Chiew AL, Gluud C, Brok J, Buckley NA. Interventions for paracetamol (acetaminophen) overdose. Cochrane Database Syst Rev. 2018 Feb 23;2:CD003328[↩]
6. Activated Charcoal. Medline Plus. https://medlineplus.gov/druginfo/natural/269.html[↩]
7. Charcoal and charcoal-based dentifrices. Brooks, John K. et al. The Journal of the American Dental Association , Volume 148 , Issue 9 , 661 – 670. http://jada.ada.org/article/S0002-8177(17)30412-9/fulltext[↩][↩]

What is maca root

Maca (Lepidium meyenii) is a Peruvian plant of the Brassicaceae (mustard) family cultivated for more than 2000 years, which grows exclusively in the central Andes between 4000 and 4500 m altitude ¹. Preparations from maca root has been used for centuries in the Andes for nutrition and to enhance fertility and improve sexual function in humans and animals ¹, ², ³.

Figure 1. Maca root

Preparations from the maca root have been reported to improve sexual function in healthy populations ². Although maca is a plant extract and not a drug, it is one of the most commonly cited “natural drugs” on the Internet for the improvement of sexual desire ⁴. The hypothesis that maca root may be effective in improving sexual function is supported by several lines of evidence. Animal experiments suggest that maca has spermatogenic and fertility-enhancing activities, which are likely due to the phytosterols or phytoestrogens present in the maca ⁵. Several animal studies have shown that maca may improve sexual behaviour and enhance androgen-like effects in rats ⁶. Recent clinical trials have also suggested significant effects of maca for increasing sperm count and mobility and improving sexual function in humans ⁷, ⁸. The potential bioactive ingredients in maca include macaridine, macamides, macaene, gluosinolates, maca alkaloid, and maca nutrients ⁵. However, these data are insufficient for determining whether maca is clinically effective.

There are strong indications ⁹, ¹⁰ that the therapeutic properties of Peruvian Maca and its fertility-enhancing properties in particular, may be linked to high concentrations of Glucosinolates (benzyl and p-methoxybenzyl glucosinolate and their isothiocyanate derivatives), which represent one of the major functional groups of biologically active compounds in this herb ¹¹, ¹⁰. It has been further observed that several Glucosinolates’ concentrations determined in hypocotyls of various coloured Maca phenotypes ¹², may be linked to specific gender-and age-dependent physiological and therapeutic properties induced by oral administration of Maca preparations, as demonstrated in a series of studies on laboratory animals ¹³, and on humans using both male subjects ¹⁴ and pre- and post-menopausal women ¹⁵. It has been further found that the Maca phenotype characterised by the colour Red, has a selective therapeutic functionality affecting men after 50, with a capacity to prevent and reduce prostate hyperplasia ¹³. Black Maca phenotype was found as having a positive effect on sexual desire, aphrodisiac and fertility-enhancing properties in adult healthy men ¹⁶. On the other hand, Yellow based Peruvian Maca in a mix with other phenotypes in a traditionally-harvested Maca crop, had a positive hormone-balancing effect on pre- and post-menopausal women ¹⁷ thereby showing potential as a non-hormonal alternative to hormone replacement therapy (HRT) treatment.

As yet there is no clear understanding as to which precisely-defined chemical class or group of compounds, are actually responsible for the medicinal functionality of specific phenotypes of Peruvian Maca with their gender- and age-linked activity. Many of the reported compound classes in plants other that Maca have medicinal functionality such as Catechins from Green tea (Camellia sinensis) which are known for their high anti-oxidant value, Amides in Echinacea species which are associated with the immunomodulatory functions of this herb, Carbolines, containing well known MAO (monoaminooxidase) inhibitors having direct effect on hormone metabolism with various effects on sexual function in animals and Glucosinolates and their derivatives (isothiocyanates, sulphoraphane) in Maca and other Brassica species, which are generally acknowledged to be of therapeutic importance.

Few randomized clinical trials have tested the effects of maca root on sexual function. This review ⁴ found limited evidence from four small trials that suggested that maca is effective in improving sexual desire after at least 6 weeks. The extent to which the therapeutic effects of maca depend on the type of maca used and the amount of various constituents in the preparation is unclear. The total number of trials, the total sample size, and the average methodological quality of the primary studies were too limited to draw firm conclusions. The optimum dose of maca is unknown. Single-dose studies used extract quantities ranging from 1.5 g/day to 3.0 g/day. A study was not included in the systematic review because no placebo effect was assessed ¹⁸. In such study, maca was administered in two doses (1.5 g/day and 3–0 g/day) to patients with selective-serotonin reuptake inhibitor (a group of antidepressant)-induced sexual dysfunction. The Arizona Sexual Experience Scale (ASEX) and the Massachusetts General Hospital Sexual Function Questionnaire (MGH-SFQ) were used to measure sexual dysfunction. Subjects on 3.0 g/day maca had a significant improvement in ASEX and in MGH-SFQ scores, but subjects on 1.5 g/day maca did not. Libido improved significantly based on ASEX item number 1, but not by dosing groups. Maca was well tolerated ¹⁸. But the results of that study failed to show differences between the two doses ¹⁸. The review authors concluded that more rigorous studies are required to identify the optimal dose.

In another systematic review ¹⁹ on the effect of maca root and menopausal symptoms in women, found very few rigorous trials of maca for menopausal symptoms. The results of that systematic review provided limited evidence for the effectiveness of maca as a treatment for menopausal symptoms. The review authors stated that the total number of trials, the total sample size, and the average methodological quality of the primary studies, were too limited to draw firm conclusions. Furthermore, the safety of maca root has not been proven yet ¹⁹. They added that the efficacy of maca root on women menopausal symptoms and safety should be tested in larger studies.

Maca Root and Sexual Function

Sexual dysfunctions are highly prevalent in our society worldwide, and the occurrence of sexual dysfunctions increases directly with age for both men and women ²⁰. They occur in 20–30% of men and 40–45% of women according to 18 descriptive epidemiological studies from around the world ²¹.

Most sexual problems relate to sexual desire (interest in sex) in both females and males and male erectile dysfunction (ED) ²¹. Interest in medicinal plants to treat sexual dysfunctions has increased in the last 20 years ²².

Maca has been described to improve sexual behavior in experimental animals, although conflictive results have been observed ²³. Traditionally maca has been referred to as a plant to improve fertility and as an energizer. In a randomized study ²⁴, researchers were unable to demonstrate effect of maca on penile erection in apparently healthy adult men after 12 weeks of treatment with gelatinized maca compared with results using placebo.

Recently, a systematic review has been performed on effect of maca on sexual function in humans ⁴. In that review, according to the authors only four randomized clinical trials met all the inclusion criteria.

According to the review, two randomized clinical trials suggested a significant positive effect of maca on sexual dysfunction or sexual desire in healthy menopausal women ²⁵ or healthy adult men ²⁶, respectively, while the other randomized clinical trials according to the reviewers failed to show any effects in healthy cyclists. However, analyzing results from such study, authors showed that maca extract significantly improved the self-rated sexual desire score compared to the baseline test and compared to the placebo trial after supplementation ²⁷. The effect in this study was as early as 14 days of treatment which is significantly shorter that that showed with gelatinized maca in which effects were observed after 8 weeks of treatment.

A further randomized clinical trial assessed the effects of maca in patients with mild erectile dysfunction using the International Index of Erectile Dysfunction-5 and showed significant effects on subjective perception of general and sexual well-being ²⁸.

Although evidence suggests an effect of maca on sexual desire and mild erectile dysfunction data also revealed that maca extract seems to have better effect ²⁷ than gelatinized maca ²⁶ and that of maca flour. The difference seems to be due to the fact that extract allow the concentration the secondary metabolites.

In summary, there is evidence that maca may improve sexual desire but is inconclusive an effect on erectile function.

Maca and Sperm Function

In a study in 9 apparently healthy men who had received maca for 4 months showed an increase in seminal volume, sperm count, and sperm motility ²⁹. Serum hormone levels (LH, FSH, prolactin, estradiol, and testosterone) in men were not affected by treatment with maca ²⁹.

Maca powder and maca extract were unable to activate androgen receptor-mediated transcription in prostate cancer cell lines ³⁰ or in a yeast-based hormone-dependent reporter assay ²⁵.

In summary, experimental and one clinical studies suggest that consumption of maca is associated with an increase in sperm count.

Maca as an Energizer

Maca has been shown to reduce scores in depression and anxiety inventories ¹⁸. A self-perception survey showed that maca acted as energizer compared with placebo in apparently healthy men ³¹.

Maca extract administration for 14 days significantly improved 40 km cycling time performance compared to the baseline test, but not compared to the placebo trial after supplementation.

In summary, scientific evidences suggest that maca may be an energizer.

Maca and Metabolic Syndrome

One study has been reported on effects of maca alone or combined with another supplements in patients with metabolic syndrome. The randomized placebo-controlled 90-day study assessed the effects of maca and yacon in combination with silymarin on plasma and lipoprotein lipids, serum glucose, and safety parameters in patients suffering from the metabolic syndrome.

No adverse effects were found in volunteers using silymarin (0.8 g/day), silymarin + yacon (0.8 + 2.4 g/day), and silymarin + maca (0.6 + 0.2 g/day). A moderate AST level and diastolic blood pressure increase was found in volunteers using maca (0.6 g/day) ³².

However, a randomized clinical trial in healthy men showed that gelatinized maca reduced systolic and diastolic blood pressure after 12 weeks of treatment ³¹. Moreover, maca significantly inhibited the hypertension relevant angiotensin I-converting enzyme (ACE) in vitro ³³.

In a population traditionally consuming maca, systolic blood pressure was lower than in those not consuming maca ³⁴. Similarly, AST (aspartate aminotransferase – is usually used to detect liver damage) levels were similar in those consuming and those not consuming maca ³⁴.

Maca contains high amounts of potassium ³⁵. Potassium is an important nutrient to reduce risk of hypertension ³⁶ and as a primary metabolite may be useful in patients with hypertension. In addition other secondary metabolites may be also be active to reduce blood pressure ³³.

Maca and Osteoarthritis

In a randomized double-blind study on 95 patients with osteoarthritis, a combination of Uncaria guianensis (cat’s claw; 300 mg) and maca (1,500 mg) was administered twice a day for 8 weeks and compared with a treatment with glucosamine sulfate. Both treatments substantially improved pain, stiffness, and functioning in the patients ³⁷. However, as the study did not include a placebo control group, glucosamine effects remain unclear.

Maca root dangers and side effects

Maca has been used for centuries in the Central Andes of Peru, and no toxic effects have been reported if it was consumed after boiling ³⁵. Previous review data on in vivo and in vitro studies with maca indicate that its use is safe ³⁵. Further evidence shows that aqueous and methanolic extracts of maca do not display in laboratory test tube on liver cell toxicity study ³⁸. Moreover, freeze-dried aqueous extract of maca (1 g/kg body weight) in mice did not reveal any toxic effect on the normal development of preimplanted mouse embryos ³⁹.

Results in rats show that different types of maca (black, red, and yellow) have no acute toxicity at ≤17 g of dried hypocotyls/kg body weight. Rats treated chronically for 84 days with 1 g/Kg body weight showed no side effects and a histological picture of liver similar to that observed in controls ⁴⁰. As usual doses in rats are 1-2 g/Kg body weight, it is suggested that maca is safe. Human consumption of ≤1 g/kg per day is considered safe, as well. However, as referred above in a study in patients with metabolic syndrome the administration of maca at a dose of 0.6 g/day for 90 days resulted in a moderate elevation of AST (aspartate aminotransferase – is usually used to detect liver damage) and diastolic arterial pressure ³². This has not been confirmed in other studies ³¹. Data on population of 600 subjects in the Peruvian central Andes showed that maca consumption was safety and that health status was improved ³⁴.

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2. Hudson T. Maca: new insights on an ancient plant. Integrative Medicine: A Clinician’s Journal. 2008;7(6):54–57.[↩][↩]
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7. Lepidium meyenii (Maca) improved semen parameters in adult men. Gonzales GF, Cordova A, Gonzales C, Chung A, Vega K, Villena A. Asian J Androl. 2001 Dec; 3(4):301-3. https://www.ncbi.nlm.nih.gov/pubmed/11753476/[↩]
8. Effect of Lepidium meyenii (Maca), a root with aphrodisiac and fertility-enhancing properties, on serum reproductive hormone levels in adult healthy men. Gonzales GF, Córdova A, Vega K, Chung A, Villena A, Góñez C. J Endocrinol. 2003 Jan; 176(1):163-8. https://www.ncbi.nlm.nih.gov/pubmed/12525260/[↩]
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10. Li G, Ammermann U, Quiros Q. FGlucosinolate contents in Maca (Lepidium peruvianum Chacon) Seeds, Sprouts, Mature plants and Several Derived Commercial Products. Economic Botany. 2001;55(23):255.[↩][↩]
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12. Peruvian Maca (Lepidium peruvianum): (II) Phytochemical Profiles of Four Prime Maca Phenotypes Grown in Two Geographically-Distant Locations. O Meissner H, Mscisz A, Piatkowska E, Baraniak M, Mielcarek S, Kedzia B, Holderna-Kedzia E, Pisulewski P. Int J Biomed Sci. 2016 Mar; 12(1):9-24. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4841986/[↩]
13. Dose-response effect of Red Maca (Lepidium meyenii) on benign prostatic hyperplasia induced by testosterone enanthate. Gasco M, Villegas L, Yucra S, Rubio J, Gonzales GF. Phytomedicine. 2007 Aug; 14(7-8):460-4. https://www.ncbi.nlm.nih.gov/pubmed/17289361/[↩][↩]
14. Effect of Lepidium meyenii (MACA) on sexual desire and its absent relationship with serum testosterone levels in adult healthy men. Gonzales GF, Córdova A, Vega K, Chung A, Villena A, Góñez C, Castillo S. Andrologia. 2002 Dec; 34(6):367-72. https://www.ncbi.nlm.nih.gov/pubmed/12472620/[↩]
15. Hormone-Balancing Effect of Pre-Gelatinized Organic Maca (Lepidium peruvianum Chacon): (III) Clinical responses of early-postmenopausal women to Maca in double blind, randomized, Placebo-controlled, crossover configuration, outpatient study. Meissner HO, Mscisz A, Reich-Bilinska H, Mrozikiewicz P, Bobkiewicz-Kozlowska T, Kedzia B, Lowicka A, Barchia I. Int J Biomed Sci. 2006 Dec; 2(4):375-94. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3614644/[↩]
16. [Maca (Lepidium meyenii Walp), a review of its biological properties]. Gonzales GF, Villaorduña L, Gasco M, Rubio J, Gonzales C. Rev Peru Med Exp Salud Publica. 2014; 31(1):100-10. https://www.ncbi.nlm.nih.gov/pubmed/24718534/[↩]
17. Therapeutic Effects of Pre-Gelatinized Maca (Lepidium Peruvianum Chacon) used as a Non-Hormonal Alternative to HRT in Perimenopausal Women – Clinical Pilot Study. Meissner HO, Reich-Bilinska H, Mscisz A, Kedzia B. Int J Biomed Sci. 2006 Jun; 2(2):143-59. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3614596/[↩]
18. Dording CM, Fisher L, Papakostas G, et al. A double-blind, randomized, pilot dose-finding study of maca root (L. meyenii) for the management of SSRI-induced sexual dysfunction. CNS Neuroscience and Therapeutics. 2008;14(3):182–191. https://www.ncbi.nlm.nih.gov/pubmed/18801111[↩][↩][↩][↩]
19. Maca (Lepidium meyenii) for treatment of menopausal symptoms: A systematic review. Maturitas. 2011 Nov;70(3):227-33. doi: 10.1016/j.maturitas.2011.07.017. Epub 2011 Aug 15. http://www.maturitas.org/article/S0378-5122(11)00262-3/fulltext[↩][↩]
20. Derogatis LR, Burnett AL. The epidemiology of sexual dysfunctions. Journal of Sexual Medicine. 2008;5(2):289–300. https://www.ncbi.nlm.nih.gov/pubmed/18004994[↩]
21. Lewis RW, Fugl-Meyer KS, Corona G, et al. Definitions/epidemiology/risk factors for sexual dysfunction. Journal of Sexual Medicine. 2010;7(4):1598–1607. https://www.ncbi.nlm.nih.gov/pubmed/20388160[↩][↩]
22. MacKay D. Nutrients and botanicals for erectile dysfunction: examining the evidence. Alternative Medicine Review. 2004;9(1):4–16. http://www.altmedrev.com/publications/9/1/4.pdf[↩]
23. Lentz A, Gravitt K, Carson CC, Marson L, Giuliano F. Acute and chronic dosing of Lepidium meyenii (Maca) on male rat sexual behavior. Journal of Sexual Medicine. 2007;4(2):332–340. https://www.ncbi.nlm.nih.gov/pubmed/17367428[↩]
24. Gonzales GF. Ethnobiology and Ethnopharmacology of Lepidium meyenii (Maca), a Plant from the Peruvian Highlands. Evidence-based Complementary and Alternative Medicine : eCAM. 2012;2012:193496. doi:10.1155/2012/193496. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3184420/[↩]
25. Brooks NA, Wilcox G, Walker KZ, Ashton JF, Cox MB, Stojanovska L. Beneficial effects of Lepidium meyenii (Maca) on psychological symptoms and measures of sexual dysfunction in postmenopausal women are not related to estrogen or androgen content. Menopause. 2008;15(6):1157–1162. https://www.ncbi.nlm.nih.gov/pubmed/18784609[↩][↩]
26. Gonzales GF, Córdova A, Vega K, et al. Effect of Lepidium meyenii (MACA) on sexual desire and its absent relationship with serum testosterone levels in adult healthy men. Andrologia. 2002;34(6):367–372. https://www.ncbi.nlm.nih.gov/pubmed/12472620[↩][↩]
27. Stone M, Ibarra A, Roller M, Zangara A, Stevenson E. A pilot investigation into the effect of maca supplementation on physical activity and sexual desire in sportsmen. Journal of Ethnopharmacology. 2009;126(3):574–576. https://www.ncbi.nlm.nih.gov/pubmed/19781622[↩][↩]
28. Zenico T, Cicero AFG, Valmorri L, Mercuriali M, Bercovich E. Subjective effects of Lepidium meyenii (Maca) extract on well-being and sexual performances in patients with mild erectile dysfunction: a randomised, double-blind clinical trial. Andrologia. 2009;41(2):95–99. https://www.ncbi.nlm.nih.gov/pubmed/19260845[↩]
29. Gonzales GF, Córdova A, Gonzales C, Chung A, Vega K, Villena A. Improved sperm count after administration of Lepidium meyenii (maca) in adult men. Asian Journal of Andrology. 2001;3:301–304. https://www.ncbi.nlm.nih.gov/pubmed/11753476[↩][↩]
30. Bogani P, Simonini F, Iriti M, et al. Lepidium meyenii (Maca) does not exert direct androgenic activities. Journal of Ethnopharmacology. 2006;104(3):415–417. https://www.ncbi.nlm.nih.gov/pubmed/16239088[↩]
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32. Valentová K, Stejskal D, Bartek J, et al. Maca (Lepidium meyenii) and yacon (Smallanthus sonchifolius) in combination with silymarin as food supplements: in vivo safety assessment. Food and Chemical Toxicology. 2008;46(3):1006–1013. https://www.ncbi.nlm.nih.gov/pubmed/18054420[↩][↩]
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What is alfalfa

Alfalfa (Medicago sativa Linn [Leguminosae]) is the most widely cultivated forage legume and one of the most economically valuable crops throughout the world and has been planted for more than two thousand years in China ¹. Because alfalfa is highly productive, stress tolerant, and a valuable forage crop for livestock, alfalfa is commonly known as the “father of all foods” (al-fal-fa) ². In America, alfalfa has been extensively cultivated since the arrival of Europeans. Alfalfa has been grown for a variety of purposes such as soil improvement, animal feed and medicinal uses ³.

Alfalfa is a cool season perennial legume living from three to twelve years, depending on variety and climate. The mature alfalfa plant is characterized by a strong taproot. This taproot may eventually surpass 6 m or more in length with several to many lateral roots connected at the crown when M. sativa is grown in deep, well drained, moist soils. The crown, a complex structure near the soil surface, has perennial meristem activity, producing buds that develop into stems. Tri- or multi-foliolate leaves form alternately on the stem, and secondary and tertiary stems can develop from leaf axils. A plant in a typical forage production field has between 5 and 15 stems and can reach nearly 1 m in height. Flowers vary in color yet purple, variegated, yellow, cream and white are the most common. After pollination, these flowers most commonly produce spiral-shaped seed pods.

Alfalfa sprouts are often consumed as vegetable salad. Its leaves or seeds are also sold as bulk powdered herb, capsules, and tablets for nutritional supplement in health food stores ⁴. The extracts from alfalfa sprouts, leaves, and roots have been indicated to be helpful in lowering cholesterol levels in animal and human studies ⁵, ⁶, ⁷. In addition, traditional medicinal use of alfalfa sprouts or leaves includes treatment of arthritis, kidney problems, and boils ⁸, ⁹. However, these treatments still need to be scientifically examined.

Additionally, alfalfa is an important source of nectar and pollen for honeybees in several locations around the world, including Al-Ahsa, Saudi Arabia ¹⁰. Alfalfa is a cross-pollinated plant, and pollination occurs with the help of insects, wind, and other external elements. The honeybees Apis mellifera L. and A. florea F. were found to be the most active pollinators in alfalfa flowers ¹¹.

Table 1. Alfalfa grass (seeds sprouted) nutrition facts

Alfalfa traditional medicine uses

Alfalfa has a long tradition of use as Ayurvedic and homoeopathic medicine in central nervous and digestive system disorders, and for the treatment of various other ailments ¹³. Traditionally, alfalfa is used to improve the memory, to cure kidney pain, cough, sore muscles, as a rejuvenator, antidiabetic, antioxidant, anti-inflammatory, antifungal, anti-asthmatic, antimicrobial, diuretic, galactagogue and in central nervous system (CNS) disorders ¹⁴. Alfalfa has been used by the Chinese since the sixth century to treat kidney stones, fever, gravel, dysuria and to relieve fluid retention and swelling. Ancient Indian Ayurvedic physicians used alfalfa to treat ulcers, arthritis pain and fluid retention. In Mexico alfalfa is believed to improve the memory, to cure sore muscles and inflammation. Early Americans used alfalfa to treat arthritis, boils, cancer, scurvy, and urinary and bowel problems. In Iraq, alfalfa is used in arthritis. In Turkey it is used as cardiotonic and to treat scurvy and arthritis ¹⁵.

Moreover, it is considered beneficial in bladder disorders, blood clotting disorders, boils, cough, diuresis, gastrointestinal tract disorders, breast cancer, cervical cancer, kidney disorders, prostate disorders, appetite stimulation, inflammation, increasing breast milk, asthma, indigestion, insect bites, jaundice, menopausal symptoms, allergies, increasing excretion of neutral steroids and bile acids in fecal matter, nutritional support, stomach ulcers, skin damage from radiation, galactagogue, increasing peristaltic action of the stomach and bowels, thrombocytopenic purpura, uterine stimulant, rheumatoid arthritis, scurvy, vitamin supplementation (vitamins A, C, E, K) and wound healing ¹⁴.

Alfalfa pharmacological and clinical reports

Alfalfa is used in traditional medicine due to being high in protein, calcium, and vitamins and also its low percentage of cellulose ¹⁶. Alfalfa is also traditionally used to treat diabetes ¹⁷. It contains many enzymes, including amylase, invertase, and pectinase, so it can be used as digestive aids ¹⁸. More than 20% of dry weight of alfalfa is protein, and it is the best source of Arg, His, Asp, Phe, and Cys amino acids. Alfalfa has an extremely high nutritive value; it includes vitamins A, B1, B6, B12, C, D, E, and K, niacin, pantothenic acid, biotin, folic acid, minerals, protein, and beneficial saponins ¹⁹, ²⁰.

Alfalfa consists of saponins that have heart protective effects due to cholesterol reduction, and these agents can absorb in digestive system in body ²¹. Saponins inhibit cholesterol esterase and acetyl coenzyme and carboxylase enzymes, thus, inhibiting fatty acid synthesis, which increases the ratio of HDL “good” cholesterol to LDL “bad” cholesterol, and it can be effective in reducing cardiovascular complications of diabetes ²². Saponins decrease intestinal absorption of cholesterol and increase its defecation ²³. Hypocholesterolemic activity has been reported for root saponins, when given to monkeys receiving a high-cholesterol diet ²⁴. Several other studies indicate that the ingestion of alfalfa reduces cholesterol absorption and atherosclerotic plaque formation in animals ²⁵, ²⁶, ²⁷. In a study, the ability of alfalfa plant to reduce liver cholesterol accumulation in cholesterol-fed rats was enhanced by the removal of saponins. Therefore, alfalfa saponins appear to play an important role in neutral steroid excretion, but are not essential for increasing bile acid excretion ²⁸. Alfalfa saponins have been shown to decrease cholesterolemia without changing the levels of high density lipoprotein-HDL cholesterol; hence, they reduced the total cholesterol/high density lipoprotein-cholesterol ratio in macaque monkeys. Furthermore, they decreased intestinal absorption of cholesterol, increased fecal excretion of endogenous and exogenous neutral steroids and bile acids, and decreased the percentage distribution of fecal deoxycholic and lithocholic acids ²⁹.

Khaleel et al. ³⁰ performed a study and showed that highest saponin content extract just before fruiting stage (free from both coumestrol and canavanine) of M. sativa exhibited significant hypocholesterolemic and antiatherosclerotic activity. This study proved that alfalfa was found to safely reduce natural cholesterol and to possess a strong anti-atherosclerotic activity. The extracts produced the most significant decrease in total cholesterol and LDL-cholesterol by 85.1 and 88%, respectively, of the corresponding levels in hypercholesterolemic rabbits. This decrease was more significant than that produced by gemfibrozil (73 and 74%) upon concomitant administration with a cholesterol enriched diet using the same animal model at the tested dose level. Moreover, it was also observed that all alfalfa preparations produced significant antioxidant properties.

Alfalfa is a rich source of vitamins and phytoestrogens, so it is used as a food additive in many developed countries ³¹. Extract of the leaves from M. sativa has been shown to be used in treatment of neurovegetative menopausal symptoms in women. Hot flushes and night sweating completely disappeared with the treatment of M. sativa extract. The plant product induced a significant increase in prolactin and thyroid stimulating hormone response to thyroid releasing hormone. Basal levels of estradiol, luteinizing hormone, follicle stimulating hormone, prolactin, and thyroid stimulating hormone were unchanged. Thus, alfalfa suggested having a central slight antidopaminergic action without side effects ³². In addition, because of its mentioned therapeutic effects, it is used as herbal drug in many countries. Previous animal studies (rabbits and rats) showed that adding alfalfa seed in animal diet reduced triglycerides and LDL, improved HDL levels, and decreased blood glucose ³³, ³⁴. Therefore, alfalfa leaves are traditionally used in South Africa as an effective treatment for diabetes ³⁵, ³⁶. Alfalfa causes stimulation of insulin secretion. It also improves insulin function in reducing the plasma glucose, but its effects on the blood lipids have not been investigated widely ³⁷. In a laboratory study involving lab rats induced to have Type 1 diabetes (insulin deficiency), rats that were fed aqueous extract of alfalfa significantly reduces blood sugar levels, triglycerides, cholesterol, LDL “bad” cholesterol and increased HDL “good” cholesterol levels ²². Previous test tube study reported increase of insulin secretion up to 3-folds in the presence of alfalfa extraction ³⁸. High concentrations of manganese in alfalfa have been reported as a possible reason of hypoglycemia ³⁹. Oral administration of alfalfa seeds triggered reduction of blood lipoprotein level in diabetics. Alfalfa is a phytoestrogens source ⁴⁰. Phytoestrogens are nonsteroidal plant-derived compounds with biological activity similar to estrogen ⁴¹. Phytoestrogens increased liver lipid biosynthesis from glucose, so it decreased glucose concentration in blood and improved repair and turnover rate of cell membrane. The results of this study ⁴² indicate that the diameter and number of pancreatic islets were significantly increased in diabetic rats treated with the extract compared with diabetic controls.

Furthermore in the same lab rat study ²² oral administration of alfalfa extract (with 250 mg/kg dose) decreased liver enzyme concentration in blood, and this decrease is more significant in 500 mg/kg dose, so alfalfa extraction causes reduction of liver damage. The study author concluded that alfalfa extract causes reduction of liver enzymes that is maybe due to improved diabetes and inhibition of lipid peroxidation ²².

Recently, Kundan and Anupam have shown that alfalfa exhibited significant antioxidant and cerebroprotective effects against ischemia and reperfusion insult in mice ⁴³. Pretreatment with alfalfa extract (100 or 200 mg/kg orally) markedly reduced cerebral infarct size, xanthine oxidase, superoxide anion and thiobarbituric acid-reactive substance levels, significantly restored reduced glutathione, superoxide dismutase and total tissue sulfhydryl levels and attenuated impairment in short-term memory and motor coordination. In addition, alfalfa directly scavenged free radicals generated against a stable radical 1,1-diphenyl-2-picrylhydrazyl and, superoxide anion radicals generated in phenazine methosulfate-nicotinamide adenine dinucleotide systems, and also inhibited xanthine dehydrogenase/xanthine oxidase conversion and resultant superoxide anion production.

Alfalfa toxicity and side effects

Both M. sativa seed and herb have been reported to induce a systemic lupus erythematosus (SLE)-like syndrome in female monkeys ⁴⁴, ⁴⁵. This activity has been attributed to canavanine, a non-protein amino acid constituent, which has been found to have effects on human immunoregulatory cells in vitro ⁴⁶. Re-activation of quiescent SLE in humans has been associated with the ingestion of alfalfa tablets which, following analysis, were found to contain canavanine ⁴⁷. It was not stated whether the tablets contained seed or herb material. Canavanine is known to be toxic to all animal species because it is a structural analogue of arginine and may interfere with the binding of this amino acid to enzymes and its incorporation into proteins. Alfalfa seeds are reported to contain substantial quantities of canavanine (8.33-13.6 mg/kg), whereas the herb is stated to contain amounts that are considerably less ⁴⁸.

“Auto-immune diseases” such as multiple sclerosis (MS), lupus (systemic lupus erythematosus, SLE), rheumatoid arthritis (RA), or other conditions: Alfalfa might cause the immune system to become more active, and this could increase the symptoms of auto-immune diseases. If you have an auto-immune condition, it’s best to avoid using alfalfa until more is known.

Kidney transplant: There is one report of a kidney transplant rejection following the three-month use of a supplement that contained alfalfa and black cohosh. This outcome is more likely due to alfalfa than black cohosh. There is some evidence that alfalfa can boost the immune system and this might make the anti-rejection drug cyclosporine less effective.

Pancytopenia has been associated with human ingestion of ground alfalfa seeds (80-160 g/day), which were taken to lower plasma cholesterol concentrations ²⁹. Dietary studies using alfalfa top saponins in the diet of rats and monkeys showed no evidence of toxicity and serum lipid concentrations were lowered ⁴⁹. In addition, when alfalfa top saponins were given to cholesterol-fed animals, a reduction in serum lipid concentrations was observed. Alfalfa top saponins are reported to be free of the SLE-inducing substance that is present in the seeds ⁵⁰. Negative results were documented for alfalfa when tested for mutagenicity using Salmonella strains TA98 and TA100 ⁵¹.

Consultation is a necessity for a health care practitioner prior to prescribe use of alfalfa if undergoing hormone replacement therapy or taking birth control medication or using blood thinners ⁴⁴.

Hormone-sensitive condition such as breast cancer, uterine cancer, ovarian cancer, endometriosis, or uterine fibroids: Alfalfa might have the same effects as the female hormone estrogen. If you have any condition that might be made worse by exposure to estrogen, don’t use alfalfa.

Diabetes: Alfalfa might lower blood sugar levels. If you have diabetes and take alfalfa, monitor your blood sugar levels closely.

Alfalfa might lower the body’s absorption of dietary iron.

Alfalfa might interfere with the way the body takes in and uses vitamin E.

Alfalfa and Medicine Interactions

Medications that decrease the immune system (Immunosuppressants)

Alfalfa might increase the immune system. By increasing the immune system, alfalfa might decrease the effectiveness of medications that decrease the immune system.

Some medications that decrease the immune system include azathioprine (Imuran), basiliximab (Simulect), cyclosporine (Neoral, Sandimmune), daclizumab (Zenapax), muromonab-CD3 (OKT3, Orthoclone OKT3), mycophenolate (CellCept), tacrolimus (FK506, Prograf), sirolimus (Rapamune), prednisone (Deltasone, Orasone), corticosteroids (glucocorticoids), and others.

Medications that increase sensitivity to sunlight (Photosensitizing drugs)

Some medications can increase sensitivity to sunlight. Large doses of alfalfa might also increase your sensitivity to sunlight. Taking alfalfa along with medication that increase sensitivity to sunlight could make you even more sensitive to sunlight, increasing the chances of sunburn, blistering or rashes on areas of skin exposed to sunlight. Be sure to wear sunblock and protective clothing when spending time in the sun.

Some drugs that cause photosensitivity include amitriptyline (Elavil), Ciprofloxacin (Cipro), norfloxacin (Noroxin), lomefloxacin (Maxaquin), ofloxacin (Floxin), levofloxacin (Levaquin), sparfloxacin (Zagam), gatifloxacin (Tequin), moxifloxacin (Avelox), trimethoprim/sulfamethoxazole (Septra), tetracycline, methoxsalen (8-methoxypsoralen, 8-MOP, Oxsoralen), and Trioxsalen (Trisoralen).

Birth control pills (Contraceptive drugs)

Some birth control pills contain estrogen. Alfalfa might have some of the same effects as estrogen. However, alfalfa is not as strong as the estrogen in birth control pills. Taking alfalfa along with birth control pills might decrease the effectiveness of birth control pills. If you take birth control pills along with alfalfa, use an additional form of birth control such as a condom.

Some birth control pills include ethinyl estradiol and levonorgestrel (Triphasil), ethinyl estradiol and norethindrone (Ortho-Novum 1/35, Ortho-Novum 7/7/7), and others.

Estrogens

Large amounts of alfalfa might have some of the same effects as estrogen. However even large amounts of alfalfa are not as strong as estrogen pills. Taking alfalfa along with estrogen pills might decrease the effects of estrogen pills.

Some estrogen pills include conjugated equine estrogens (Premarin), ethinyl estradiol, estradiol, and others.

Medications for diabetes (Antidiabetes drugs)

Alfalfa might decrease blood sugar. Diabetes medications are also used to lower blood sugar. Taking alfalfa along with diabetes medications might cause your blood sugar to go too low. Monitor your blood sugar closely. The dose of your diabetes medication might need to be changed.

Some medications used for diabetes include glimepiride (Amaryl), glyburide (DiaBeta, Glynase PresTab, Micronase), insulin, pioglitazone (Actos), rosiglitazone (Avandia), and others.

Contraindications

People with a history of lupus or a family history of systemic lupus erythematosus should avoid alfalfa supplements ⁴⁴, ⁴⁵, ⁵².

Alfalfa seeds should not be ingested during pregnancy or lactation ⁵². There is some evidence that alfalfa may act like estrogen, and this might affect the pregnancy.

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What is licorice

Licorice (American) or liquorice (British) is the root of Glycyrrhiza glabra from which a sweet flavor can be extracted ¹. Licorice is harvested from the plants’ roots and underground stems. The licorice plant is a herbaceous perennial legume native to southern Europe and parts of Asia, such as India. It is not botanically related to anise, star anise, or fennel, which are sources of similar flavoring compounds. Anise oil is often used instead of licorice root to flavor licorice candy.

In ancient Egypt, licorice was not eaten as strips or ropes of candy but was made into a sweet liquid drink ². The extract of the plant called Glycyrrhiza is derived from the ancient Greek term ‘glykos’, meaning sweet, and ‘rhiza’, meaning root. Glycyrrhiza was indulged upon by many prophets and pharaohs.

Licorice is a popular sweetener found in many soft drinks, food products, snacks and herbal medicines. Most licorice is used as a flavoring agent for tobacco, particularly US blend cigarettes, to which licorice lends a natural sweetness and a distinctive flavour and makes it easier to inhale the smoke by creating bronchodilators, which open up the lungs ³. Licorice flavors are also used as candies or sweeteners, particularly in some European and Middle Eastern countries.

Centuries ago, licorice root was used in Greece, China, and Egypt for stomach inflammation and upper respiratory problems. Licorice is one of the most widely prescribed herbs in Chinese medicine. It is used to treat gastric ulcers when administered 20 to 30 minutes before meals through lining the stomach wall. The processed form of licorice (deglycyrrhizinated form of licorice or DGL) is not associated with adverse effects and can be used to treat peptic ulcer disease in combination with antacids (this combination has been marketed as Caved-S) ². However, licorice is rarely used nowadays because of its side effects and the emergence of other more powerful classes of medications for treatment of peptic ulcers.

Today, people use licorice root as a dietary supplement for digestive problems, menopausal symptoms, cough, and bacterial and viral infections. Licorice supplements are available as capsules, tablets, and liquid extracts. People also use it as a shampoo.

Figure 1. Licorice root

Figure 2. Licorice plant

Benefits of licorice root

A number of studies of licorice root in people have been published, but not enough to support the use for any specific health condition.

• Glycyrrhizin—a compound found in licorice root—has been tested in a few clinical trials in hepatitis C patients, but there’s currently not enough evidence to determine if it’s helpful ⁴. Laboratory studies done in Japan (where an injectable glycyrrhizin compound is used in people with chronic hepatitis C who do not respond to conventional treatment) suggest that glycyrrhizin may have some effect against hepatitis C ⁵.

• Also in Japan, glycyrrhizin has been given intravenously for treatment of patients with chronic hepatitis B with improvement in liver functions and occasionally complete recovery. It was suggested that glycyrrhizin is able to suppress the secretion of both hepatitis B surface antigen and its intracellular transport ⁶, ⁷.

• There’s some evidence that topical licorice extract may improve skin rash symptoms, such as redness, swelling, and itching.

• In women, licorice has been used in conjunction with spironolactone in the treatment of polycystic ovary syndrome (PCOS) ⁸. This estrogenic activity of licorice has been well documented ⁹.

• Studies of licorice root extracts in people for cavities, mouth ulcers, and oral yeast infections have returned mixed results ¹⁰.

•  Agarwal and colleagues demonstrated the beneficial effect of licorice gargle in reducing the risk of postoperative sore throat ¹¹.

• Other beneficial effects of licorice include its role in bone metabolism which was described by Mattarello and colleagues ¹² who demonstrated an increased parathyroid hormone and urinary calcium levels from baseline value in healthy women after 2 months of therapy. The postulated mechanism was the estrogen-like activity of isoflavans which are one of the constituents of licorice roots.

• Understanding the mechanism of action of licorice promoted its therapeutic benefit in several groups of patients. The binding of licorice to the MR explains its utility in patients with Addison’s disease. These effects are due to the affinity of glycyrrhetinic acid for mineralocorticoid receptor (see Figure 3 below) in addition to its plasma concentration being more than 5000 fold the concentration of aldosterone ¹³. Patients with postural hypotension caused by diabetic autonomic neuropathy have also shown improvement with licorice ingestion ¹⁴. Bernardi and colleagues studied the effects of prolonged ingestion of graded doses of licorice on serum potassium level in healthy volunteers ¹⁵. A significant fall in plasma potassium concentration from 4.3 to 3.5 mmol/liter was noticed, which occurred at the dose of 800 mg or more daily. An important clinical application for this was provided by Farese and colleagues, who demonstrated the use of licorice as an important tool to maintain predialysis potassium levels within a safe limit to decrease the risk of hyperkalemic (high blood potassium) arrhythmias in patients on chronic dialysis ¹⁶.

Licorice side effects and toxicity

After oral ingestion of licorice in humans, its main constituent, glycyrrhizic acid, is hydrolyzed to glycyrrhetic acid by intestinal bacteria possessing a specialized ß-glucuronidase. Glycyrrhetic acid is a 200–1000 times more potent inhibitor of 11-ß-hydroxysteroid dehydrogenase than glycyrrhizic acid; therefore, its pharmacokinetics is more relevant after oral administration.

The active metabolites in licorice extract which are glycyrrhizic acid and glycyrrhetic acid can lead to a syndrome known as apparent mineralocorticoid excess ¹⁷. These side effects arise from the inhibition of the enzyme 11-ß-hydroxysteroid dehydrogenase and subsequent increase in the activity of cortisol. This effect is physiologically important because cortisol binds as avidly as aldosterone to the mineralocorticoid receptor ¹⁸. One form of this enzyme 11-ß-hydroxysteroid dehydrogenase type 2 (11-ß-HSD2) is mainly restricted in the kidneys to the aldosterone-sensitive sites in the collecting tubules. Licorice also has a mineralocorticoid-like activity not only by blocking 11-ß-HSD2 but also by directly binding to mineralocorticoid receptor ¹⁹.

Figure 3. Licorice mineralocortioid like activity

Note: Different mechanisms of action of licorice through inhibition of 11-ß-hydroxysteroid dehydrogenase type 2, 5 ß-reductase (which metabolizes aldosterone) and its direct action on the mineralocorticoid receptors causing sodium reabsorption and potassium secretion. MR= mineralocorticoid receptor; 11-ß-HSD 2 = 11-ß-hydroxysteroid dehydrogenase type 2.

Licorice main constituent, glycyrrhizic acid, mimics mineralocorticoids in its action (sodium reabsorbtion and potassium secretion) ². The extent of metabolic and acid–base derangement can occasionally be severe enough to cause serious complications such as high blood pressure and low potassium levels, which could lead to heart and muscle problems ²⁰.

Excessive consumption of licorice (more than 2 mg/kg/day of pure glycyrrhizinic acid, a licorice component) may result in adverse effects, and over consumption should be suspected clinically in patients presenting with otherwise unexplained hypokalemia (low blood potassium) and muscle weakness ².

The complication associated with most fatalities is the arrhythmogenic effect of licorice mediated by hypokalemia and subsequent QT prolongation and possible torsade de pointes. The prognosis in the reported cases was poor, with six out of nine cases experiencing cardiac arrest ²¹, ²², ²³, ²⁴. Some reports described a picture of heart failure and acute pulmonary edema which mostly followed a licorice binge ²⁵, ²⁶. In these cases, recovery was the rule after implementing antifailure measures. A few cases presented with generalized edema which responded well to cessation of licorice and diuretic therapy ²⁷, ²⁸.

Several reports demonstrated the occurrence of ocular complications related to licorice ingestion ²⁹, ³⁰, ³¹. The underlying pathogenesis involves vasospasm of the optic nerve blood vessels leading to transient monocular or binocular visual loss/aberrations. All patients who experienced transient visual loss/aberrations had resolution of their visual symptoms; the aid of hyperbaric oxygen was required for one patient.

Table 1. Complications related to excess licorice intake

Some side effects are thought to be due to a chemical called glycyrrhizic acid. Licorice that has had this chemical removed (called DGL for deglycyrrhizinated licorice) may not have the same degree of side effects.

Taking licorice root containing glycyrrhizinic acid with medications that reduce potassium levels such as diuretics might be bad for your heart.

Factors that increase sensitivity to glycyrrhizin ²:

• Hypokalemia
• Prolonged gastrointestinal transit time
• Decreased 11-ß-hydroxysteroid dehydrogenase-2 activity
• Hypertension
• Anorexia nervosa
• Old age
• Female sex

Pregnant women should avoid using licorice root as a supplement or consuming large amounts of it as food.

• A Finnish study of mothers and their young children suggested that eating a lot of actual licorice root during pregnancy may harm a child’s developing brain, leading to reasoning and behavioral issues, such as attention problems, rule-breaking, and aggression ³².

Black Licorice Overdose

As it turns out, you really can overdose on candy—or, more precisely, black licorice ³³.

Days before the biggest candy eating holiday of the year, the Food and Drug Administration (FDA) encourages moderation if you enjoy snacking on the old fashioned favorite.

So, if you’re getting your stash ready for Halloween, here’s some advice from FDA:

• If you’re 40 or older, eating 2 ounces of black licorice a day for at least two weeks could land you in the hospital with an irregular heart rhythm or arrhythmia.

FDA experts say black licorice contains the compound glycyrrhizin, which is the sweetening compound derived from licorice root. Glycyrrhizin can cause potassium levels in the body to fall. When that happens, some people experience abnormal heart rhythms, as well as high blood pressure, edema (swelling), lethargy, and congestive heart failure.

FDA’s Linda Katz, M.D., says last year the agency received a report of a black licorice aficionado who had a problem after eating the candy. And several medical journals have linked black licorice to health problems in people over 40, some of whom had a history of heart disease and/or high blood pressure.

FDA’s Linda Katz, M.D., says potassium levels are usually restored with no permanent health problems when consumption of black licorice stops.

Figure 4. Black licorice

If you have a fondness for black licorice, FDA is offering this advice:

• No matter what your age, don’t eat large amounts of black licorice at one time.
• If you have been eating a lot of black licorice and have an irregular heart rhythm or muscle weakness, stop eating it immediately and contact your healthcare provider.
• Black licorice can interact with some medications, herbs and dietary supplements. Consult a health care professional if you have questions about possible interactions with a drug or supplement you take.

How much licorice is too much ?

The main difficulty with licorice dosing lies in its availability in various forms such as candies, beverages, supplements and extracts that contain different amounts of the active components of licorice. In the United States, the manufacture of some dietary supplements, including licorice, is not closely regulated. Licorice and its derivatives, including ammoniated glycyrrhizin, are generally recognized as safe (GRAS) for use in foods by the US Food and Drug Administration (FDA) (21 CFR 184.1408). This chapter of regulations includes descriptions, specifications and maximum use levels (Table 2) for licorice and licorice derivatives. The FDA assumes that glycyrrhizin levels in foods do not pose a health hazard, provided that these foods are not consumed in excess.

Table 2. US Food and Drug Administration limitations for the use of licorice and its derivatives in foods

In 1991, the European Union proposed a provisional figure of 100 mg/day as the upper limit for ingestion of glycyrrhizin (approximately the amount found in 60–70 g licorice) ³⁵. In April 2003, the Scientific Committee on Food confirmed an upper limit of 100 mg/day ³⁶. This was based on data from human volunteer studies. The Dutch Nutrition Information Bureau advised against daily glycyrrhizin consumption in excess of 200 mg, assumed to correspond to 150 g of licorice confectionery ³⁷.

Licorice fluid extracts contain approximately 10–20% glycyrrhizin; typical doses of 2–4 ml deliver 200–800 mg. A review concluded that about 2% of the regular consumers have a daily intake of glycyrrhizinic acid of over 100 mg/day ³⁸. In 1994, Walker and Edwards demonstrated that a daily oral intake of 1–10 mg of glycyrrhizin, which corresponds to 1–5 g licorice, has been estimated to be a safe dose for most healthy adults ³⁹. Two studies on healthy volunteers were published. In 1994, Bernardi and colleagues ¹⁵ administered daily doses of 108, 217, 380 and 814 mg glycyrrhizic acid, as ‘licorice pills’ for 4 weeks to four groups of 3 male and 3 female healthy volunteers. No observed-adverse-effect level (NOAEL) based on the study report was 217 mg/person/day. At higher dose levels, sodium retention and depression of plasma renin and aldosterone levels were observed. Female participants were slightly more sensitive to glycyrrhizinic acid than male participants. Two years later, in the double-blinded randomized placebo-controlled study by Bijlsma and colleagues ⁴⁰, four groups of 10 healthy female volunteers received orally 0, 1, 2 or 4 mg of pure glycyrrhizinic acid/kg/day for 8 weeks. In this study the No observed-adverse-effect level (NOAEL) for glycyrrhizinic acid was 2 mg/kg/day. The European committee considered that the No observed-adverse-effect level (NOAEL) obtained in the study by Bijlsma and colleagues is more appropriate because this study comprised a larger group of volunteers (40 volunteers in contrast to 24 volunteers), a longer period of exposure (8 weeks in contrast to 4 weeks) and inclusion of a placebo control group.

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What is triphala ?

Triphala ¹ is a herbal formulation composed of 3 fruits: Indian gooseberry Amalaki (Emblica officinalis), Bibhitaki (Terminalia belerica), and Haritaki (Terminalia chebula) in a 1:1:1 ratio. Triphala is mentioned throughout the ancient literature of Ayurvedic medicine as a tridoshic rasayana because it promotes longevity and rejuvenation in patients of all constitutions and ages ². Triphala is classified as a tridoshic rasayana, meaning that the “energetics are appropriate for Vata, Pitta, and Kapha or all types of patients” ². Charak, the great Indian Ayurvedic physician, describes rasayanas as having the qualities of supporting strength and immunity ³. Triphala has being traditionally used in India as therapeutic aid to regulate the process of digestion, mild laxative and antimicrobial properties in various ailments like prevention of dental caries/plaque formation, gingival health and periodontal diseases ⁴, ⁵, ⁶.

According to traditional Ayurvedic medicine, Triphala formulation is shown to have various medicinal properties which promote health, longevity of life when used in a proper manner ⁷. It is also shown to have anti-inflammatory, antioxidant, and antimicrobial properties (because of the gallic acid content), and is a known to be hepatoprotective in nature ⁸, ⁹, ¹⁰. Triphala is reported to correct constipation thus helping to improve digestion ⁷. Triphala can be ingested over a long period of time without any side effects ⁷. The phenolic and nonphenolic composition of triphala are active against both pathogenic and nonpathogenic bacterial strains ¹¹, ¹²; when used as mouth wash, it effectively reduced the number of mutant streptococci in saliva ¹³.

Various studies have been done to evaluate the antifungal property of triphala ¹⁴.

Fruits of Triphala

Emblica officinalis (Amalaki)

Main chemical ingredient: Vitamin C, carotene, nicotinic acid, riboflavin, and tannins ¹⁵.

Amalaki is known by the botanical name Emblica officinalis and also known in Sanskrit as Dhatri (The nurse), which is a reference to its incredible healing properties. Amalaki can be taken individually in powder form, a decoction or as a confection. Amalaki fruit is known to be one of the best rasayanas in Ayurveda, with anti-oxidant and anti-aging properties. It has its beneficial role in cancer, diabetes, liver treatment, heart trouble, ulcer, anemia, and various other diseases. Similarly, it has application as immunomodulatory, anti-pyretic, analgesic, cytoprotective, anti-tussive, and gastroprotective agent. Additionally, it is useful in memory enhancing, ophthalmic disorders, and lowering cholesterol level. It is also helpful in neutralizing snake venom and as an anti-microbial agent against Escherichia coli, K. ozaenae, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, S. paratyphi A, S. paratyphi B and Serratiamarcescens. The drug is not reported to have any side-effects even after prolonged use ¹⁶.

Figure 1. Embilica officinalis (Indian gooseberry)

Terminalia chebula (Hiritaki or Black myrobalan)

Main chemical ingredient: Tannins, anthraquinones, and polyphenolic compounds ¹⁵.

Terminalia chebula is a plant species belonging to the genus Terminalia, family Combretaceae. The fruit of the tree has been used as traditional medicine for household remedy against various human ailments, since antiquity. Terminalia chebula has been extensively used in Ayurveda, Unani, and Homoeopathic medicine and has become a cynosure of modern medicine. Terminalia chebula is rich in tannin. The chief constituents of tannin are chebulic acid, chebulagic acid, corilagin, and gallic acid.

Terminalia chebula exhibited anti-bacterial activity against a number of Gram-positive and Gram-negative human pathogenic bacterial species. It also exhibits anti-fungal and anti-viral properties. It has also shown anti-mutagenic/anti-carcinogenic activity, antioxidant activity, adaptogenic and anti-anaphylactic activities, immunomodulatory activity, cytoprotective and radioprotective activity. It is also effective in hypolipidemia/hypercholesterolemia, improving gastro-intestinal motility with anti-spasmodic activity, diabetes, retinopathy, and wound healing ¹⁷.

Figure 2. Haritaki (Terminalia chebula)

Terminalia belerica (Bibhitaki)

Main chemical ingredient: Gallic acid, tannic acid, and glycosides ¹⁵.

Terminalia bellerica Roxb. (Combretaceae), commonly known as “belleric myrobalan” and locally as “bahera,” is a large deciduous tree, found throughout central Asia and some other parts of the world. Its fruit is used in folk medicine to treat asthma, cancer, colic, diarrhea, dysuria, headache, hypertension, inflammations, and pain. The plant is reported to contain termilignan, thannilignan, anolignan B, gallic acid, ellagic acid, ί-sitosterol, arjungenin, belleric acid, bellericosidem, flavonoids, and tannins. T. belerica possesses antioxidant, anti-spasmodic, bronchodilatory, hypercholesterolemic, anti-bacterial, cardioprotective, hepatoprotective, hypoglycemic, and hypotensive properties ¹⁸.

Figure 3. Bibhitaki (Terminalia belerica)

Main Chemical Constituents of Triphala

Tannins

Tannin is a general descriptive name for a group of polymeric phenolic substances capable of tanning leather or precipitating gelatin from solution, a property known as astringency. This group of compounds, especially green teas and red wines, has received a great deal of attention in recent years since they can cure or prevent a variety of ills. Many human physiological activities, such as stimulation of phagocytic cells, host-mediated tumor activity, and a wide range of anti-infective actions, have been assigned to tannins. One of their molecular actions is to complex with proteins through so-called non-specific forces such as hydrogen-bonding and hydrophobic effects, as well as by covalent bond formation. Thus, their mode of anti-microbial action may be related to their ability to inactivate microbial adhesins, enzymes, and cell envelope transport proteins ¹⁹.

Quinones

Quinones are aromatic rings with two ketone substitutions. They are ubiquitous in nature and are characteristically highly reactive. The individual redox potential of the particular quinine-hydroquinone pair is very important in many biological systems. Vitamin K is a complex naphthoquinone with anti-hemorrhagic activity. In addition to providing a source of stable free radicals, quinones are known to complex irreversibly with nucleophilic amino acids in proteins, often leading to inactivation of the protein and loss of function. For that reason, the potential range of quinone anti-microbial effects is great. Probable targets in the microbial cell are surface-exposed adhesins, cell wall polypeptides, and membrane-bound enzymes. Quinones may also render substrates unavailable to the microorganism ¹⁹.

Flavones, flavonoids, and flavonols

Flavones are phenolic structures containing one carbonyl group (as opposed to the two carbonyls in quinones). The addition of a 3-hydroxyl group yields a flavonol. Flavonoids are also hydroxylated phenolic substances, but occur as a C6-C3 unit linked to an aromatic ring. Since they are known to be synthesized by plants in response to microbial infection, it should not be surprising that they have been found in vitro to be effective anti-microbial substances against a wide array of microorganisms. Their activity is probably due to their ability to complex with extracellular and soluble proteins and to complex with bacterial cell walls. More lipophilic flavonoids may also disrupt microbial membranes. These compounds have been shown to inhibit Vibrio cholera O1, Shigella, Streptococcus mutansin vitro. Inhibition of isolated bacterial glucosyltransferases in S. mutans, and reduction of fissure caries by about 40% has also been demonstrated ¹⁹.

Gallic acid

Gallic acid is a common phyto-constituent present in all three herbs used in Triphala. It is reported to possess hepatoprotective and antioxidant activity. It also suppresses growth of cancer cells.

Vitamin C

Fruit juice of Emblica officinalis (Indian gooseberry Amalaki) contains the highest vitamin C (478.56 mg/100 mL) content. The fruit when blended with other fruits boosted their nutritional quality in terms of vitamin C content. Vitamin C in EO accounts for approximately 45-70% of the antioxidant activity ¹⁶. Evidences have been reported for the relation between vitamin C and periodontal disease. Significant gum bleeding can occur in vitamin C deficiency. Vitamin C along with bioflavonoid helps to speed up the healing process ¹⁶.

Triphala benefits

Ayurvedic physicians use Triphala for many ailments but most importantly to treat various gastrointestinal disorders, as digestive, mild laxative at normal doses, bowel tonic at low dose, purgative at high doses, carminative, expectorant, antispasmodic, and bronchodilator ². Triphala is widely used to treat constipation, as an intestinal cleanser, as a gastrointestinal tract tonifier, to fasten peristalsis and to support both digestion and absorption of food. Triphala is also useful in maintaining serum cholesterol levels, to improve circulation, relax the bile duct and as a hepatoprotective agent ²⁰. Daily use of Triphala may also promote proper digestion and absorption of food, reduce serum cholesterol levels, improve circulation, relax bile ducts, prevent immunosenescence, maintain homeostasis of the endocrine system, and increase production of red blood cells and hemoglobin ²⁰.

The major active constituents of triphala are the tannins, gallic acid, ellagic acid, and chebulinic acid, which are potent antioxidants that may account, at least in part, for the observed immunomodulatory activity of the formula ²¹, ²², ²³. Triphala also contains other bioactive compounds such as flavonoids (e.g., quercetin and luteolin), saponins, anthraquinones, amino acids, fatty acids, and various carbohydrates ²². In addition, Triphala-derived polyphenols such as chebulinic acid are also transformed by the human gut microbiota into bioactive metabolites, which have demonstrated potential in vitro to prevent oxidative damage ²⁴.

Variable efficacy of herbal therapies

A number of factors, including variability in herbal source, processing, bioavailability, digestion, and absorption of herbal components, cause the true efficacy of herbs on human health to be highly variable. This variability is known to be at least partially due to inherent variation in the gut microbiota that act on the ingested components of herbal remedies and transform them into compounds with increased bioabsorption and bioactivity. These features have confounded the true efficacy of herbal remedies as it pertains to the maintenance of human health and/or the ability to reverse chronic disease states.

The increased popularity of herbal remedies such as Triphala has led to dramatic improvements in the processing of crude plant materials that serve to maximize the absorption of otherwise poorly absorbed plant components. Despite these improvements, these preparations still display pronounced variability in efficacy, which is likely related to the natural variation in composition of gut microbiota species that catalyze the biotransformation of herbal components. This response variability is not unique to herbs and, in fact, may be the case for virtually all health-promoting compounds ingested by humans (e.g., polyphenolic compounds derived from plants).

Triphala in gastrointestinal health

Triphala is perhaps most well known for its use in general gastrointestinal health. Animal studies have shown that both aqueous and alcohol-based extracts of Triphala prevent diarrhea ²⁵. Triphala also induces enteroprotective effects, which are likely due, at least in part, to the high antioxidant content. In a rodent model, Triphala replenished depleted protein in the intestinal villi of the brush border as well as glutathione and phospholipid levels; the formula simultaneously decreased myeloperoxidase and xanthine oxidase levels in intestinal epithelium ²⁶. In rats, Triphala exerted a gastroprotective effect on stress-induced ulcer ²⁷. One human clinical trial that investigated the use of Triphala in patients with gastrointestinal disorders reported that treatment reduced constipation, mucous, abdominal pain, hyperacidity, and flatulence while improving the frequency, yield, and consistency of stool ²⁸. Triphala also reduced colitis in a mouse model, and the treatment effect was attributed to antioxidant effects and high levels of flavonoids contained in Triphala ²⁹.

Triphala in diabetes and for weight loss

Deregulation of eating behavior is common in industrialized countries. Studies have demonstrated the potential of Triphala as a therapeutic agent for weight loss and reduction of body fat. In an animal study, Triphala was administered for 10 weeks to diet-induced obese mice ³⁰. Triphala treatment decreased the percentage of body fat, body weight, and energy intake. Triphala also decreased total cholesterol, triglycerides, and low-density lipoprotein cholesterol in the experimental group compared with the control group. In a 12-week, double-blind, randomized placebo-controlled trial, human subjects treated with Triphala lost ∼5 kg compared with the placebo control group ³¹. Mean fasting blood sugar and fasting serum insulin levels were also reduced in the treated compared with control subjects. Given the global obesity epidemic, more treatment options are necessary to reduce the associated healthcare burden.

Triphala exerts hypoglycemic effects. Patients with type 2 diabetes are likely to have high postprandial blood glucose levels, especially after consuming carbohydrates. Elevated blood glucose results from the breakdown of carbohydrates by the digestive enzymes, alpha-amylase and alpha-glucosidase, and the reduced ability of cells to take in glucose from the blood. Past studies report that Triphala may exert actions similar to diabetic pharmaceutical drugs by inhibiting digestive enzymes and may decrease absorption of glucose through inhibition of glycolytic enzymes, thereby reducing blood glucose levels. One study demonstrated the inhibitory potential of Triphala on pancreatic glycolytic enzymes, namely alpha-amylase and alpha-glucosidase, which break down larger polysaccharides into glucose molecules that enter the blood stream ³¹.

The role that Triphala plays in inhibiting starch digestion and absorption, thereby decreasing postprandial hyperglycemia, is similar to that of diabetes pharmaceutical drugs, such as miglitol and acarbose, which also target these glycolytic enzymes. In addition, Triphala decreased serum glucose levels in normal and alloxan-induced diabetic rats ³². A clinical study of noninsulin-dependent diabetes mellitus patients revealed that supplementation with 5 g of Triphala powder for 45 days significantly lowered blood glucose levels ³³. Both fasting and postprandial blood glucose were reduced, which may be due to active ingredients such as sorbitol. Constituents in Triphala, including ellagitannins and gallotannins, also enhance both PPAR-alpha and -gamma signaling, which increase insulin responsiveness and glucose uptake without inducing adipogenesis ³⁴. These polyphenols may also promote decreased blood glucose and insulin levels in diabetic patients.

Triphala may also protect diabetics and those predisposed to diabetes through inhibition of glycation enzymes. Elevated blood glucose can cause severe damage through the process of glycation, in which sugar molecules compromise protein molecules in the body, which may in turn lead to nerve damage or blindness. Due to the presence of tannins, Triphala extract was found to effectively inhibit protein glycation in vitro ³⁵. Triphala may also prevent glycation through promotion of lower blood glucose levels. As diabetes is the most prevalent endocrine disease globally, increased access to complementary hypoglycemic therapies for integrative care is needed.

Stress-reducing potential of Triphala

Stress-induced disorders such as anxiety represent the leading causes of adult disability worldwide ³⁶. Stress is a state of disharmony caused by perceived threat that is counteracted by an adaptive response to reestablish homeostasis and is associated with many chronic diseases. Animal studies have shown that Triphala protected against cold-induced stress and reversed stress-induced behavioral alterations and biochemical changes such as increased lipid peroxidation and corticosterone levels ³⁷. Triphala also prevented noise-induced stress ³⁸. In rats, Triphala prevented the noise-induced metabolic changes by mediating the antioxidant and cell-mediated immune response, and it was hypothesized that the biological mechanism is related to its antioxidant properties ³⁹, ⁴⁰. Modern humans experience high levels of stress, thus adaptogenic treatments are needed more extensively in clinical practice.

Triphala and cardiovascular health

Cardiovascular disease is a leading cause of mortality and morbidity worldwide, and hypercholesteremia is an important risk factor. Animal studies have reported the hypercholesteremic effects of Triphala. In one study, Triphala reduced the total cholesterol, low-density lipoprotein, very low-density lipoprotein, and free fatty acid levels in rats fed an atherogenic diet for 48 days ⁴¹. Another study in rats fed an atherogenic diet revealed that Haritaki, one of the herbs in Triphala, induced hypolipidemic effects in the herb-treated group. A reduction in total cholesterol, triglycerides, and total protein and elevation of high-density lipoprotein cholesterol were found in the herb-treated group compared with control group ⁴². Triphala is a powerful herb to address imbalances in the gastrointestinal tract and cardiovascular system and should be more widely studied in the context of these common diseases.

Antimicrobial potential of Triphala

Over administration of antibiotics has led to widespread drug resistance, thus it is becoming imperative that clinical researchers discover alternative and adjunctive antimicrobial agents with high efficacy. Both Triphala water decoctions (12%) and ethanol extracts (14%) have demonstrated antibacterial activity in vitro against bacterial isolates derived from patients infected with human immunodeficiency virus ⁴³; the ethanol extracts were reported to have greater in vitro antimicrobial action against these species compared with the aqueous extracts, which may indicate lower solubility of the aromatic antibiotic compounds.

In addition, other studies report that these extracts also exert broad-spectrum antimicrobial action against antibiotic-resistant bacteria isolated from human subjects. The aqueous extracts (1:6) have demonstrated greater efficacy compared with the ethanol extracts (1:6) on pathogenic bacteria such as Escherichia coli and Staphylococcus aureus ⁴⁴. In vitro, ethanol extracts of Triphala (100 mg/mL) components exhibited specific antimicrobial activity against multidrug-resistant clinical bacterial isolates ⁴⁵. Thus, Triphala was reported to exert antibacterial effects on both gram-positive and gram-negative species in vitro and demonstrated potential for further investigation as a complementary or adjunct antimicrobial therapy.

In addition to antimicrobial effects against oral bacteria, Triphala has also demonstrated the potential to eradicate enteric pathogens in vitro. One study tested the effects of Triphala aqueous extract (200 mg/mL) against enteric bacterial pathogens in vitro and found that Triphala possesses strong antibacterial effects against Staphylococcus epidermidis and S. aureus and moderate effects against Proteus vulgaris, Pseudomonas aeruginosa, and Salmonella typhi ⁴⁵. In addition to antibacterial effects, Triphala is also known to exhibit antifungal properties. Triphala exerts antifungal action against Asperigillus species and has been reported to inhibit the fungus by up to 37.96% in vitro. In particular, the aqueous extracts (1:1) of fresh fruits were found to be more effective than dry fruits ⁴⁶. Thus, the formula represents a promising antimicrobial candidate in need of further study.

The Potential of Triphala in Oral Care

Triphala has been used traditionally in Ayurvedic medicine as an antimicrobial agent ⁴⁷. Numerous controlled clinical trials have shown that Triphala significantly reduces the abundance of oral bacteria, dental plaque, and gingivitis in human subjects ⁴⁸, ⁴⁹. For example, Triphala is effective against Enterococcus faecalis, one of the most difficult to eliminate oral pathogens that are commonly isolated in chronic periodontitis. One study revealed that Triphala (5 mg/mL) in 10% dimethyl sulfoxide (DMSO) was equally or more effective at eliminating E. faecalis in vitro compared with NaOCl, a common irrigant used during root canals ⁵⁰. Triphala was more effective than 0.5% and 1% NaOCl solution, but equally effective as 2.5% and 5% solutions.

In addition, another group reported that Triphala in 10% DMSO was more effective than 5.25% NaOCl solution against E. faecalis biofilms on ex vivo tooth substrate and suggested the extract as an alternative in the context of clinical root canal irrigation ⁵¹. A study using human primary teeth ex vivo revealed that Triphala suspended in 10% DMSO (1:3) exhibited significant antibacterial activity compared with control as well as higher antibacterial activity compared with 3% NaOCl ⁵². In vitro studies using Triphala ethanol extract have reported similar antimicrobial effects against E. faecalis compared with 2.5% NaOCl ⁵³. Thus, Triphala may represent a potential therapy to eliminate E. faecalis as more side-effects and larger risk are associated with NaOCl solution treatment.

Dental caries, or cavities of the teeth, is a common infection associated with humans. Examining the use of Triphala as an oral antimicrobial agent, one study reported that Triphala dissolved in 10% DMSO exhibited a significant antibacterial effect ex vivo on extracted human mandibular premolars against Streptococcus mutans, which is one of the most prevalent oral pathogens responsible for dental cavities ⁵⁴.

Human clinical trials using Triphala water decoction as a mouthwash report that it exerts comparable efficacy compared with chlorhexidine gluconate germicidal mouthwash in the prevention of dental caries.45,46 For example, a study in human subjects revealed that Triphala (6%) mouthwash promoted a significant reduction in oral streptococcus colonies. Oral streptococcus levels were measured after using a 6% Triphala mouthwash or 0.2% chlorhexidine mouthwash twice per day for 48 h and for 7 days; Streptococcus levels were reduced by 17% and 44%, respectively, in the Triphala-treated group ⁴⁸. The researchers concluded that Triphala was as effective as 0.2% chlorhexidine mouthwash given that the results of the Triphala treatment were similar to the chlorhexidine-treated group. Another double-blind human clinical trial also reported significant reductions in oral streptococcus levels at 5 and 60 min after rinsing with 15 mL aqueous Triphala extract (10%) mouthwash ⁵⁵.

In addition, a double-blind, randomized human clinical trial reported that Triphala (10%) mouthwash is effective against dental plaque and gingivitis in teenagers ⁵⁶. The study reported Triphala as equally effective in antiplaque and antigingivitis activity compared with chlorhexidine. Moreover, a clinical study in children on the effects of Triphala (0.6%) mouthwash on dental plaque, gingival inflammation, and microbial growth also compared its efficacy with a commercially available chlorhexidine mouthwash. The results indicated that both the germicidal chlorhexidine (0.1%) and Triphala mouthwash were equally effective in reducing plaque and increasing gingival health after 9 months; however, Triphala was more effective than chlorhexidine in reducing microbial cell counts ⁵. A double-blind, randomized clinical trial in young adults also compared the efficacy of Triphala (0.6%) and chlorhexidine (0.12%) mouthwash for 21 days and reported a similar reduction in both plaque and gingival scores for both the Triphala- and chlorhexidine-treated groups ⁵⁷. Triphala mouthwash treatment has also shown promise to reverse precancerous oral lesions associated with tobacco use in young adults ⁵⁸.

In periodontal diseases, matrix metalloproteinases (MMPs) degrade extracellular matrix proteins in a spectrum of processes that include tissue remodeling such as the connective tissue destruction observed in periodontitis. Ex vivo Triphala studies using extracted gingival tissue have demonstrated a greater reduction of MMP-9 activity in patient-derived white blood cells treated with Triphala compared with patient-derived cells treated with the standard antibiotic drug ⁵⁹. In treated tissue extracts, Triphala (1.5 mg/mL) reduced MMP-9 activity by 77%, while doxycycline (300 μg/mL) reduced MMP-9 activity by 59%. Thus, MMP inhibitors are important adjunctive therapies in periodontitis treatment and Triphala may represent a candidate to investigate in greater detail in this context. In addition, given the observed effectiveness of Triphala mouthwash compared with standard treatment, additional clinical trials should be performed to identify the potential for integration in dentistry.

Radioprotective effects of Triphala

Studies have concluded that Triphala may help prevent and reverse DNA damage and mutagenesis ⁶⁰. The prevention of DNA damage is important given that it is often an initiating event in carcinogenesis. Research in animal models and in vitro has shown that Triphala is effective in prevention of mutagenesis induced by both chemical- and radiation-induced damage ⁶¹. An in vitro study found that Triphala eliminated reactive oxygen species in HeLa cells exposed to ionizing X-radiation or bleomycin, both of which generate DNA strand breaks through the generation of reactive oxygen species ⁶². In addition, gamma-radiation-induced plasmid DNA strand break was inhibited by Triphala in vitro. The rasayana formulation also inhibited radiation-induced lipid peroxidation in rat liver microsomes and demonstrated the ability to scavenge free radicals such as superoxide. Importantly, the high levels of phenolic compounds such as gallic acid were attributed to the free radical scavenging activity ⁶¹.

In animal models, Triphala intervention reduced radiation-induced mortality by 60% in mice fed Triphala for only 7 days before whole-body gamma-irradiation ⁶³. Triphala reversed the increased xanthine oxidoreductase and decreased the superoxide dismutase activity that was observed post-irradiation. Treatment with Triphala also prevented DNA damage in murine white blood cells and spleen cells post-irradiation. Triphala may play a protective role against oxidation, even when administered after exposure.

In addition, other animal studies have reported significantly reduced acute intestinal damage after ionizing radiation exposure in groups fed Triphala (1 kg/g) for at least 5 days before radiation treatment ⁶⁴. Moreover, studies have demonstrated that Triphala feeding before gamma-radiation exposure reduced radiation sickness and mortality in mice ⁶⁵. Triphala was reported to scavenge hydroxyl, superoxide anion, and nitric oxide free radicals in a dose-dependent manner in vitro ⁶⁵. Triphala aqueous extract feeding for 5 days before exposure was also reported as protective against gamma-radiation in mice at a dose of 10 mg/kg, which was 1/28 of the calculated LD50 dose ⁶⁶. Thus, the antioxidant and free radical scavenging activities of Triphala were concluded to serve a role in its protective effect against ionizing radiation. Human clinical trials to further elucidate the mechanisms of radioprotective action and clinical utility are required.

Anti-tumor activity of Triphala

Triphala has been investigated as a potential antineoplastic agent.61 Numerous studies have been performed in this context and have shown that Triphala exerts an antineoplastic effect on many cancer cell lines, including those of the breast, prostate, colon, and pancreas ⁶⁷. Data in cell lines show that Triphala has a differential modulatory effect on normal and cancer cell lines. Triphala induces cytotoxicity in cancer cells, which showed increases in intracellular reactive oxygen species, but not normal cells. Excised tumor tissue from Triphala-fed mice compared with controls suggested that apoptosis induction may have mediated reduced tumor growth ⁶⁸.

Preclinical studies using in vitro and in vivo models report that Triphala inhibits cancer growth in both cell and in vivo models and the effects are mediated through the ERK and p53 pathways ⁶⁹. In addition, methanol extract of Triphala suppressed proliferation and induced p53-independent apoptosis in human colon cancer stem cells ⁶⁷. Triphala suppressed the expression of oncogenes, c-Myc and Cyclin D1, and thus Wnt pathway signaling to reduce proliferation and resistance to apoptosis. Triphala-induced apoptotic induction occurred through the intrinsic mitochondrial apoptotic signaling pathway. Moreover, one clinical trial reported that Triphala powder treatment in healthy humans increased cytotoxic T cells and NK cells in the experimental group compared with the control group ⁷⁰. Thus, Triphala shows potential as an antineoplastic agent and thus should be systematically explored for potential as an adjunct therapy in the management of colon and other cancers.

Antioxidant activity of Triphala and eye health

Antioxidant effects of Triphala have the potential to help maintain eye health. Triphala is a rich source of vitamin C and flavonoids. One study used Triphala as a pretreatment in selenite-induced cataracts in mice. Triphala significantly restored glutathione levels in eye lenses. Triphala also increased the activities of antioxidant enzymes, such as superoxide dismutase, catalase, glutathione-S-transferase, and glutathione peroxidase, in the lenses of the experimental group when compared with the control group. While 100% of the mice in the control group developed cataracts, only 20% of the mice pretreated with Triphala developed cataracts. This effect may be linked to the antioxidant activity of Triphala ⁷¹.

Anti-inflammatory effects of Triphala

Chronic inflammation is deleterious and affects most major chronic health conditions. Triphala has shown promise as an anti-inflammatory agent. In one study, Triphala performed better or equivalent when compared with standard drug treatment for a variety of biochemical measurements of inflammation.19 In addition, Triphala significantly reduced inflammatory markers as well as bone and cartilage degradation in arthritic rats ⁷². In this study, Triphala extract was significantly more effective than the nonsteroidal anti-inflammatory drug, indomethacin, in ameliorating arthritic and inflammatory effects. Triphala reduced expression of inflammatory mediators such as IL-17, COX-2, and RANKL through inhibition of NF-κB activation. Another study found that Triphala increased antioxidant levels and decreased lipid peroxidation in the tissues of arthritic rats ⁷³.

In lipopolysaccharide-stimulated macrophages, Triphala treatment suppressed production of inflammatory mediators (such as TNFα, IL-1β, IL-6, MCP-1, VEGF, NO, and PGE2), intracellular free radicals, inflammatory enzymes (such as iNOS and COX-2), and lysosomal enzyme release ⁷⁴. Chebulagic acid, a constituent in Triphala, was found to inhibit COX and 5-LOX, which are both major enzymes involved in inflammation and carcinogenesis ⁷⁵. Triphala also increased antioxidant activity in mice after induction of nephrotoxicity from bromobenzene. Triphala ameliorated nephrotoxic effects by upregulating antioxidant enzymes, superoxide dismutase, glutathione-S-transferase, and glutathione peroxidase. Lipid peroxidation and markers of kidney dysfunction were reduced in the Triphala-treated group compared with controls ⁷⁶. The anti-inflammatory effects of Triphala should be investigated in greater detail.

Antiaging effects of Triphala

Triphala extract exerted highly protective antiaging effects on human skin cells in vitro. Triphala extract affects gene expression of human skin cells, stimulating collagen-1 and elastin-synthesizing genes and antioxidant genes responsible for the cellular antioxidant, SOD-2. Triphala extract was found to inhibit melanin production and hyperpigmentation due to the presence of protective phytochemicals. Furthermore, Triphala extract exhibited significant free radical scavenging activity on hydrogen peroxide-induced cell damage and senescence ⁷⁷. These results demonstrate potential dermal antiaging effects of Triphala, such as increasing collagen and elastin, increasing cellular antioxidants, and decreasing hyperpigmentation.

Triphala and the gut microbiome

It is known that phytochemicals in Triphala such as quercetin and gallic acid promote the growth of Bifidobacteria and Lactobacillus species while inhibiting the growth of undesirable gut residents such as E. coli ⁷⁸. In addition, the lactic acid bacteria possess enzymatic activity (e.g., tannase) to degrade plant tannins such as gallic acid contained in Triphala ⁷⁹. For example, Triphala-derived polyphenols such as chebulinic acid are transformed by the human gut microbiota into metabolites such as urolithins, which have the potential to prevent oxidative damage ²⁴. The authors speculate that the bioactivity of Triphala is elicited by the gut microbiome to generate a widened spectrum and abundance of anti-inflammatory compounds.

Triphala-induced benefits in both the elderly and persons of all ages may be enhanced by coadministration of specific probiotic species. Thus, probiotic formulations consisting of bacterial species capable of mediating the increased digestion, bioabsorption, and bioactivity of Triphala may increase and make more uniform the response and impact of Triphala treatment on human populations. Further studies are required to determine the full effect of Triphala on gut microbiota and the potential of specific probiotics to increase the efficacy of the herb.

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What is cinnamon

Cinnamon (Cinnamomum zeylanicum and Cinnamon cassia) is a spice obtained from the inner bark of several tree species from the genus Cinnamomum that belongs to the Lauraceae family ¹. Used as a spice for thousands of years, cinnamon comes from the bark of the cinnamon tree. Preparation of cinnamon involves stripping of the outer bark of the tree and letting the inner bark to dry and curl up into its customary cinnamon quills. Cinnamon is available in either its whole quill form (Cinnamon sticks) or as ground powder in the market ². The aromatic bark of the various cinnamon species tree is used worldwide for culinary purposes, but is also used in Ayurvedic and traditional Chinese medicine for its hypoglycaemic, digestive, antispasmodic and antiseptic properties ³, ⁴. Overall, approximately 300 species have been identified among the cinnamon genus, with trees being scattered all over the world ⁵, ⁶. Cassia cinnamon, native to China, is the most common type sold in the United States and Canada. Ceylon cinnamon (Cinnamomum verum or Cinnamomum zeylanicum), native to Sri Lanka, is common in other countries and is known as “true” cinnamon ⁷. Indonesia (Cinnamomum burmanii) and China (Cinnamomum cassia) contribute 76% of the world’s production of cinnamon ⁸. Essential oils are made from the bark, leaves, or twigs of cassia cinnamon.

Cinnamon is mainly used in the aroma and essence industries due to its fragrance, which can be incorporated into different varieties of foodstuffs, perfumes, and medicinal products ⁹. The most important constituents of cinnamon are cinnamaldehyde and trans-cinnamaldehyde (Cin), which are present in the essential oil, thus contributing to the fragrance and to the various biological activities observed with cinnamon ¹⁰. A study on Cinnamomum osmophloeum (C. osmophloeum) indicated that the essential oil from cinnamon leaves contains a high level of trans-cinnamaldehyde (Cin). Consequently, Cinnamomum osmophloeum is also used as an alternative spice for cinnamon cassia ¹¹. One of the major constituents of essential oil extracted from Cinnamomum zeylanicum named (E)-cinnamaldehyde has an antityrosinase activity ¹², while cinnamaldehyde is the principal compound responsible for this activity ¹³.

Cinnamon bark contains procyanidins and catechins ¹⁴. The components of procyanidins include both procyanidin A-type and B-type linkages ¹⁵. These procyanidins extracted from cinnamon and berries also possess antioxidant activities ¹⁶.

Cinnamon has a long history as a traditional medicine, including for bronchitis. Today, some people use cinnamon as a dietary supplement for gastrointestinal problems, loss of appetite, and diabetes, among other conditions. Cinnamon is used in capsules, teas, and extracts.

However, studies done in humans don’t support using cinnamon for any health condition ¹⁷, ¹⁸, ¹⁹. A 2013 systematic review ²⁰ of 10 randomized controlled clinical trials in people with type 1 or type 2 diabetes suggests that cinnamon doesn’t help to reduce levels of glucose or glycosylated hemoglobin A1c (HbA1c), a long-term measure of glucose (blood sugar) control. A 2012 Cochrane systematic review ¹⁹ of 10 randomized controlled trials involving a total of 577 participants found insufficient evidence to support the use of cinnamon for type 1 or type 2 diabetes. A product containing cinnamon, calcium, and zinc didn’t improve blood pressure in a small study of people with type 2 diabetes ¹⁷.

Traditional uses of cinnamon

In addition to being used as a spice and flavoring agent, cinnamon is also added to flavor chewing gums due to its mouth refreshing effects and ability to remove bad breath ²¹. Cinnamon can also improve the health of the colon, thereby reducing the risk of colon cancer ²².

Cinnamon is a coagulant and prevents bleeding ²³. Cinnamon also increases the blood circulation in the uterus and advances tissue regeneration ²⁴. This plant plays a vital role as a spice, but its essential oils and other constituents also have important activities, including antimicrobial ²⁵, antifungal ²⁶, antioxidant ²⁷, and antidiabetic ²⁸.

Cinnamon has been used as anti-inflammatory ²⁹, antitermitic ³⁰, nematicidal ³¹, mosquito larvicidal ³², insecticidal ³³, antimycotic ³⁴ and anticancer agent ³⁵. Cinnamon has also been traditionally used as tooth powder and to treat toothaches, dental problems, oral microbiota, and bad breath ³⁶. At present Cinnamon is sold as both a preventative and therapeutic supplement for many ailments including, metabolic syndrome, insulin resistance, type 2 diabetes, hyperlipidaemia and arthritis ².

Note: All of the traditional uses outlined above have not be proven by well conducted scientific randomized clinical studies in human. Most of the traditional uses of cinnamon have all be done in laboratory test tubes and using animals as test subjects. We only list them here only to show what ailments and treatments cinnamon has been used traditionally and not because cinnamon has been proven to work in humans. More research are required before their benefits in human can be confirmed. Until larger and more rigorous clinical studies are available on the safety and efficacy of cinnamon as well as the feasibility of it as a component of integrative medicine, we recommend that patients continue to follow existing recommendations from their health care professionals.

Cinnamon nutrition facts

Almost every part of the cinnamon tree including the bark, leaves, flowers, fruits and roots, has some medicinal or culinary use. The volatile oils obtained from the bark, leaf, and root barks vary significantly in chemical composition, which suggests that they might vary in their pharmacological effects as well ³⁷. The different parts of the plant possess the same array of hydrocarbons in varying proportions, with primary constituents such as; cinnamaldehyde (bark), eugenol (leaf) and camphor (root) ³⁸. Thus cinnamon offers an array of different oils with diverse characteristics, each of which determines its’ value to the different industries. For example the root which has camphor as the main constitute, has minimal commercial value unlike the leaf and bark ³⁹. It is this chemical diversity that is likely to be the reason for the wide-variety of medicinal benefits observed with cinnamon.

Table 1. Ground cinnamon nutrition content

Table 2. Chemical constituents of different parts of cinnamon

Health benefits of cinnamon

Studies have been consistent in showing that diabetic patient adherence to current conventional treatment protocols are poor ⁴¹. Diabetic patients are 1.6 times more likely than non-diabetics to use a complementary and alternative medicine for a host of reasons ⁴². The worldwide trend for the use of complementary and alternative medicines in diabetes has increased with an overall prevalence ranging between 30-57 % ⁴³.

Recent estimates show that over 80 % of people living in developing countries depend on complementary and alternative medicine for treatment of health conditions ⁴⁴. More recently in 2013, Herman estimates the cost of Complementary and Integrative Medicine in the US to be 34 billion dollars ⁴⁵.

Cinnamon has been a research interest in patients with diabetes since the 1990s ²⁰. Various data from randomized clinical trials show conflicting results of the effects of cinnamon on glycemic and lipid parameters. Consumption of 1 to 1.2 g/d was associated with an increase in fasting plasma glucose levels ⁴⁶, ⁴⁷ and hemoglobin A1c levels ⁴⁸, ⁴⁶; however, others have reported reductions in glycemic parameters at doses between 1 to 6 g/d ⁴⁹, ⁵⁰, ⁵¹ and in hemoglobin A1c ⁴⁹, ⁵⁰, ⁵¹. The same conflict occurs in lipid parameters, at 1 g/d total cholesterol ⁴⁶, LDL-“bad” Cholesterol ⁵², ⁵⁰ and triglyceride levels were reported to increase ⁴⁶, while HDL-“good” Cholesterol levels decreased ⁵², ⁴⁸. Only 1 trial identified statistically significant increases in hemoglobin A1c and fasting plasma glucose levels; however, this trial was published only as a research brief, so many of the study characteristics were unclear ⁴⁶. Based on currently available literature, cinnamon may have a beneficial effect on fasting plasma glucose, LDL-“bad” Cholesterol, HDL-“good” Cholesterol and triglyceride levels in patients with type 2 diabetes ²⁰. But there is no statistically significant effect on hemoglobin A1c (HbA1c). Contrary to the finding of this study, a Cochrane Review ¹⁹ involving oral monopreparations of cinnamon (primarily Cinnamomum cassia) in tablet or capsule form, at an average daily dose of 2 g, for a mean period of 11 weeks, found that in people with type 1 or type 2 diabetes mellitus, orally administered cinnamon (Cinnamomum cassia) in tablet or capsule form, at a dose of 0.5 to 6 g daily for a period of four to 16 weeks, is no more effective than placebo at improving glycosylated haemoglobin A1c (HbA1c) or serum insulin levels. The effect of cinnamon on fasting and postprandial blood glucose levels is inconclusive ¹⁹.

In conclusion, cinnamon should not be used in place of conventional medical care or to delay seeking care if you have health problems. This is particularly true if you have diabetes.

Cinnamon side effects

Side effects of cinnamon have been poorly documented in humans, because most research focusing on safety and efficacy has been conducted either in test tubes or in animals. Potential side effects found in animal studies include liver toxicity that results from coumarin isolates found in cinnamon cassia bark, decreased platelet counts, increased the risk of bleeding and allergy/hypersensitivity to cinnamon ⁵³.

Cassia cinnamon contains varying amounts of a chemical called coumarin, which might cause or worsen liver disease. In 2008, The European Food Safety Authority considered toxicity of coumarin, a significant component of cinnamon, and confirmed a maximum recommended tolerable daily intake (TDI) of 0.1 mg of coumarin per kg of body weight. Coumarin is known to cause liver and kidney damage in high concentrations and metabolic effect in humans with CYP2A6 polymorphism ⁵⁴. Based on this assessment, the European Union set a guideline for maximum coumarin content in foodstuffs of 50 mg per kg of dough in seasonal foods, and 15 mg per kg in everyday baked foods ⁵⁴.

According to the maximum recommended tolerable daily intake (TDI) of 0.1 mg of coumarin per kg of body weight, which is 7 mg of coumarin for a body weight of 70 kg.

• Cinnamomum cassia (Chinese cinnamon) has 0.10 mg – 12.18 milligrams of coumarin per grams of cinnamon.
• Cinnamomum verum (Ceylon cinnamon) has less than 0.10 milligrams of coumarin per grams of cinnamon.

In most cases, cassia cinnamon doesn’t have enough coumarin to make you sick. However, for some people, such as those with liver disease, taking a large amount of cinnamon (coumarin) might worsen their condition ⁵⁵. These possible effects may be a concern for patients with impaired liver function, concurrent anticoagulant or antiplatelet therapy, patients on antilipidemic agents, and those who are known to be hypersensitive to cinnamon or its components. There are reports of nonimmunologic contact urticaria occurring in people coming into contact with cinnamon products ⁵⁶; however, because no human studies have been conducted to test this theory, these concerns remain hypothetical. Isolated case reports of cinnamon-induced stomatitis venenata (inflammation of the mucous lining of any of the structures in the mouth) secondary to contact allergy have been reported with consumption of the herb as a flavouring agent ⁵⁷. However, there have been no documented adverse effects associated with the oral administration of cinnamon extract in clinical studies to date.

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25. Gende LB, Floris I, Fritz R, Eguaras MJ. Antimicrobial activity of cinnamon (Cinnamomum zeylanicum) essential oil and its main components against paenibacillus larvae from argentine. Bulletin of Insectology. 2008;61(1):1–4.[↩]
26. Antifungal activities of essential oils and their constituents from indigenous cinnamon (Cinnamomum osmophloeum) leaves against wood decay fungi. Wang SY, Chen PF, Chang ST. Bioresour Technol. 2005 May; 96(7):813-8. https://www.ncbi.nlm.nih.gov/pubmed/15607195/[↩]
27. Kim N, Sung H, Kim W. Effect of solvents and some extraction conditions on antioxidant activity in cinnamon extracts. Korean Journal of Food Science and Technology. 1993;25(3):204–209.[↩]
28. The evaluation of long-term effects of cinnamon bark and olive leaf on toxicity induced by streptozotocin administration to rats. Onderoglu S, Sozer S, Erbil KM, Ortac R, Lermioglu F. J Pharm Pharmacol. 1999 Nov; 51(11):1305-12. https://www.ncbi.nlm.nih.gov/pubmed/10632089/[↩]
29. Study on the antiinflammatory activity of essential oil from leaves of Cinnamomum osmophloeum. Chao LK, Hua KF, Hsu HY, Cheng SS, Liu JY, Chang ST. J Agric Food Chem. 2005 Sep 7; 53(18):7274-8. https://www.ncbi.nlm.nih.gov/pubmed/16131142/[↩]
30. Anti-inflammatory activities of essential oils and their constituents from different provenances of indigenous cinnamon (Cinnamomum osmophloeum) leaves. Tung YT, Yen PL, Lin CY, Chang ST. Pharm Biol. 2010 Oct; 48(10):1130-6. https://www.ncbi.nlm.nih.gov/pubmed/20815702/[↩]
31. Nematicidal Activity of Cassia and Cinnamon Oil Compounds and Related Compounds toward Bursaphelenchus xylophilus (Nematoda: Parasitaphelenchidae). Kong JO, Lee SM, Moon YS, Lee SG, Ahn YJ. J Nematol. 2007 Mar; 39(1):31-6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2586484/[↩]
32. Chemical composition and mosquito larvicidal activity of essential oils from leaves of different Cinnamomum osmophloeum provenances. Cheng SS, Liu JY, Tsai KH, Chen WJ, Chang ST. J Agric Food Chem. 2004 Jul 14; 52(14):4395-400. https://www.ncbi.nlm.nih.gov/pubmed/15237942/[↩]
33. Insecticidal activities of leaf essential oils from Cinnamomum osmophloeum against three mosquito species. Cheng SS, Liu JY, Huang CG, Hsui YR, Chen WJ, Chang ST. Bioresour Technol. 2009 Jan; 100(1):457-64. https://www.ncbi.nlm.nih.gov/pubmed/18396039/[↩]
34. Bioactivity of cinnamon with special emphasis on diabetes mellitus: a review. Bandara T, Uluwaduge I, Jansz ER. Int J Food Sci Nutr. 2012 May; 63(3):380-6. https://www.ncbi.nlm.nih.gov/pubmed/22007625/[↩]
35. Aqueous cinnamon extract (ACE-c) from the bark of Cinnamomum cassia causes apoptosis in human cervical cancer cell line (SiHa) through loss of mitochondrial membrane potential. Koppikar SJ, Choudhari AS, Suryavanshi SA, Kumari S, Chattopadhyay S, Kaul-Ghanekar R. BMC Cancer. 2010 May 18; 10():210. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2893107/[↩]
36. Comparative study of cinnamon oil and clove oil on some oral microbiota. Gupta C, Kumari A, Garg AP, Catanzaro R, Marotta F. Acta Biomed. 2011 Dec; 82(3):197-9. https://www.ncbi.nlm.nih.gov/pubmed/22783715/[↩]
37. [Comparison studies on chemical constituents of essential oil from Ramulus Cinnamomi and Cortex Cinnamomi by GC-MS]. Shen Q, Chen F, Luo J. Zhong Yao Cai. 2002 Apr; 25(4):257-8. https://www.ncbi.nlm.nih.gov/pubmed/12583177/[↩]
38. Cinnamon and health. Gruenwald J, Freder J, Armbruester N. Crit Rev Food Sci Nutr. 2010 Oct; 50(9):822-34. https://www.ncbi.nlm.nih.gov/pubmed/20924865/[↩]
39. Paranagama PA, Wimalasena S, Jayatilake GS, Jayawardena AL, Senanayake UM, Mubarak AM. A comparison of essential oil constituents of bark, leaf root and fruit of cinnamon (cinnamomum zeylanicum Blum), grown in Sri Lanka. J Natl Sci Found Sri. 2010;29:147–153.[↩]
40. United States Department of Agriculture Agricultural Research Service. National Nutrient Database for Standard Reference Release 28. https://ndb.nal.usda.gov/ndb/search/list[↩]
41. Cramer JA. A systematic review of adherence with medications for diabetes. Diabetes Care. 2004;27(5):1218–24. doi: 10.2337/diacare.27.5.1218. https://www.ncbi.nlm.nih.gov/pubmed/15111553[↩]
42. Garrow D, Egede LE. Association between complementary and alternative medicine use, preventive care practices, and use of conventional medical services among adults with diabetes. Diabetes care. 2006;29(1):15–19. doi: 10.2337/diacare.29.01.06.dc05-1448. https://www.ncbi.nlm.nih.gov/pubmed/16373889[↩]
43. Bell RA, Suerken CK, Grzywacz JG, Lang W, Quandt SA, Arcury TA. Complimentary and alternative medicine use among adults with diabetes in the United Sates. Altern Ther Health Med. 2006;12(5):16–22. https://www.ncbi.nlm.nih.gov/pubmed/17017751[↩]
44. Ranasinghe P, Jayawardena R, Galappathy P, Constantine GR, de Vas gunawardena N, Katulanda P. Efficacy and safety of ‘true’ cinnamon (Cinnamomum zeylanicum) as a pharmaceutical agent in diabetes: a systematic review and meta-analysis. Diabet Med. 2012;29(12):1480–92. doi: 10.1111/j.1464-5491.2012.03718.x. https://www.ncbi.nlm.nih.gov/pubmed/22671971[↩]
45. Herman PM. Evaluating the Economics of Complementary and Integrative Medicine. Global Advances in Health and Medicine. 2013;2(2):56-63. doi:10.7453/gahmj.2013.002. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3833528/[↩]
46. Effect of cinnamon on glucose and lipid levels in non insulin-dependent type 2 diabetes. Blevins SM, Leyva MJ, Brown J, Wright J, Scofield RH, Aston CE. Diabetes Care. 2007 Sep; 30(9):2236-7. https://www.ncbi.nlm.nih.gov/pubmed/17563345/[↩][↩][↩][↩][↩]
47. Dietary cinnamon supplementation and changes in systolic blood pressure in subjects with type 2 diabetes. Wainstein J, Stern N, Heller S, Boaz M. J Med Food. 2011 Dec; 14(12):1505-10. https://www.ncbi.nlm.nih.gov/pubmed/21861719/[↩]
48. Cinnamon supplementation does not improve glycemic control in postmenopausal type 2 diabetes patients. Vanschoonbeek K, Thomassen BJ, Senden JM, Wodzig WK, van Loon LJ. J Nutr. 2006 Apr; 136(4):977-80. http://jn.nutrition.org/content/136/4/977.long[↩][↩]
49. Cinnamon improves glucose and lipids of people with type 2 diabetes. Khan A, Safdar M, Ali Khan MM, Khattak KN, Anderson RA. Diabetes Care. 2003 Dec; 26(12):3215-8. https://www.ncbi.nlm.nih.gov/pubmed/14633804/[↩][↩]
50. Glycated haemoglobin and blood pressure-lowering effect of cinnamon in multi-ethnic Type 2 diabetic patients in the UK: a randomized, placebo-controlled, double-blind clinical trial. Akilen R, Tsiami A, Devendra D, Robinson N. Diabet Med. 2010 Oct; 27(10):1159-67. https://www.ncbi.nlm.nih.gov/pubmed/20854384/[↩][↩][↩]
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53. Nutrition recommendations and interventions for diabetes: a position statement of the American Diabetes Association. American Diabetes Association., Bantle JP, Wylie-Rosett J, Albright AL, Apovian CM, Clark NG, Franz MJ, Hoogwerf BJ, Lichtenstein AH, Mayer-Davis E, Mooradian AD, Wheeler ML. Diabetes Care. 2008 Jan; 31 Suppl 1():S61-78. https://www.ncbi.nlm.nih.gov/pubmed/18165339/[↩]
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What is fenugreek

Fenugreek, also known as its scientific name of trigonella foenum-graecum L., leguminosae, belongs to the plant family fabaceae (or leguminosae). It grows in most of the countries around world with major production in Asia, Europe and American including United States. Fenugreek is an herb extract prepared from the dried seeds of Trigonella foenum-graecum (sicklefruit fenugreek), a plant belonging to the pea family (Fabaceae) ¹. Fenugreek is in the spice blend garam masala. It’s used to flavor imitation maple syrup and as a condiment ². Its extracts are also in soaps and cosmetics ². Fenugreek is native to India and northern Africa and is one of the oldest medicinal plants is continuous use. Historically, fenugreek was used for a variety of health conditions, in Chinese medicine, fenugreek seeds were used as a tonic; in Indian medicine, as a stimulant to lactation , including digestive problems and to induce childbirth; and, in many folk medicines as an aid to digestion and treatment of baldness. Today, fenugreek is used as a dietary supplement for diabetes, to stimulate milk production during breastfeeding, and for other health conditions ². It’s also used topically as a dressing for wounds or eczema. The seeds are made into capsules, powders, teas, liquid extracts, and a dressing for the skin ².

Investigation of its activity in animal models suggested that fenugreek extracts have antioxidant, antihyperlipidemic and hypoglycemic activities. Constituents of fenugreek extracts include dietary fibers, mucilages, steroid saponins, flavonoids, trigonelline, and volatile oils. The lipid- and glucose-lowering effects of fenugreek have been attributed to saponins.

• A few small studies ³ found that fenugreek may help lower blood sugar levels in people with diabetes (type 2 diabetes mellitus), but the evidence is weak ⁴. There is thus good scientific evidence to support that fenugreek is not effective in lowering blood glucose in healthy, obese or overweight subjects ⁵, ⁶.
• Some studies suggest ⁷, ⁸ —but haven’t proven—that fenugreek may increase milk production in women who are breastfeeding ⁹, ¹⁰.
• There isn’t enough scientific evidence to support the use of fenugreek for any health condition ².

The benefits of fenugreek therapy in hypercholesterolemia and diabetes in humans have not been proven in rigorously designed prospective clinical trials ². Nevertheless, fenugreek is widely used, often in combination with conventional therapies. The usual doses used to aid in the management of diabetes and hypercholesterolemia are variable, ranging from 2 to 100 grams daily taken in 2 or 3 divided doses either as capsules or as powder to prepare teas. Fenugreek preparations contain high levels of fiber, which may represent 50% of its constituents. Fenugreek is also used topically and in foods as a flavoring agent.

Fenugreek uses

Four recent patents or patent applications described usages and applications of fenugreek in managing metabolic diseases including hyperglycemia and diabetes. One patent application described making dietary supplements with fenugreek fibers to control blood glucose ¹¹. Another patent application claimed making food products with fenugreek seed powder for prevention of obesity and diabetes ¹². The third patent application disclosed an anti-diabetic composition of food supplement with fenugreek seed extract ¹³. Clinical studies with human volunteers showed a dosage form of 500 mg given once or twice daily either alone or in combination with standard, synthetic anti-diabetic drugs such as metformin and glipizide provided beneficial effects on controlling plasma glucose levels. One recently issued patent illustrated a composition with fenugreek seeds to lower glucose and cholesterol ¹⁴.

Those claims are largely supported by the findings from human clinical trials. Four such trials were conducted with type 1 and 2 diabetic patients before 2000. The first study involved non-insulin dependent diabetic patients ¹⁵. Supplementation of 15 g fenugreek seed soaked in water resulted in a significant reduction in postprandial glucose levels in 21 diabetic patients. The second study was a randomized, controlled crossover trial with 15 diabetic patients ¹⁶. A diet supplemented with 100 g of fenugreek seed powder was given daily for 10 days in treatment group (7 patients) while a regular diet was given to the control group (8 patients). Then the patients were crossed over for additional 10 days. It was found that supplementation with fenugreek seed powder significantly reduced fasting blood sugar and improved the glucose tolerance test. In the third study, ten non-insulin dependent diabetic patients were enrolled in a randomized, controlled crossover trial ¹⁷. Treatment for 5 subjects included a diet supplemented with 25 g fenugreek daily for 15 days. Without a washout period, the patients were crossed over for additional 15 days. The results showed that fenugreek supplement significantly reduced the area under the plasma glucose curve and improved glucose tolerance. In the fourth trial ¹⁸, forty patients with coronary artery disease and non-insulin-dependent diabetes mellitus and 30 healthy volunteers were given a diet containing 5 g of fenugreek for 3 months. At the end of the study, twenty patients with mild hyperglycemia exhibited a significant reduction in fasting blood sugar and postprandial glucose levels. However, the changes in patients with severe hyperglycemia and healthy subjects were not statistically significant.

Four clinical trials were carried out more recently with diabetic patients. In a small double blind and controlled study ¹⁹, twenty five newly diagnosed type 2 diabetic patients were divided into two groups, treatment and control. Twelve patients in the treatment group were supplemented with 1 g hydroalcoholic extract of fenugreek seeds whereas 13 patients in the control group received placebo capsules for daily 2 months. No significant differences in fasting blood sugar and oral glucose tolerance test were detected between the two groups. However, significant differences in the area under curve of blood glucoses and insulin sensitivity were noticed. Two relatively large clinical trials were carried out in 2005 ²⁰ and 2008 ²¹. One trial involved 60 male subjects with non-insulin dependent diabetes ²⁰. Thirty patients in one group received a daily dose of 1 g mixed powder containing equal amount of raw fenugreek seed, bitter gourd and jambu seed powder in the form of capsules whereas the other group with 30 patients consumed same dose in the form of salty biscuits for 1.5 months, followed by ingesting an increased daily dose of 2 g mixed powder for another 1.5 months. At the end of the study, a significant reduction in fasting blood sugar and post-prandial glucose levels was achieved in both groups. The other trial was conducted in 69 type 2 diabetic patients with not well controlled blood glucose levels using oral sulfonylureas ¹⁹. The treatment group with 46 patients received 18 pills of fenugreek daily while the control group with 23 patients took placebo for 12 weeks. All the patients continued their original hypoglycemic drugs during the study. Supplement with fenugreek pills in the treatment group significantly decreased fasting blood sugar, postprandial blood glucose and HbA1c levels, coupled with improved clinical symptoms. It was thus concluded that supplementation of sulfonylureas hypoglycemic drug with fenugreek was an effective therapy to manage diabetic patients with uncontrolled blood glucose with hypoglycemic drug alone. The last trial recruited 18 type 2 diabetic patients ²². The subjects were divided into two groups. One group with 11 patients received a daily dose of 10 g fenugreek seed powder in hot water whereas the other group with 7 subjects consumed the same amount of fenugreek seeds mixed with yoghurt for 8 weeks. Significant decreases in fasting blood sugar was detected in group consuming fenugreek in hot water but not in the group given fenugreek mixed with yoghurt. It was concluded that fenugreek seeds was an effective adjuvant in the control of type 2 diabetes in the form of soaked in hot water. Mixing of fenugreek seeds with yoghurt may interfere with the absorption of active ingredients of fenugreek seeds in the gastrointestinal track.

The hypoglycemic activity of fenugreek was also evaluated in three clinical trials with healthy or healthy obese volunteers. The first early trial recruited 20 male healthy subjects ²³. The treatment group received 40mg/kg aqueous extract of fenugreek seeds whereas the control group received placebo. Four hours post-ingestion, blood glucose levels were significantly reduced in the treatment group. The second trial was a single blind, randomized, crossover study and conducted in 18 healthy obese subjects ²⁴. Two treatment groups received 4g or 8g of isolated fenugreek fiber whereas the control group received a placebo. No significant changes were noticed in postprandial blood glucose levels and insulin sensitivity within 3.5 hours post-ingestion between the three groups. The third trial is a double-blind, randomized, and placebo-controlled study with 38 healthy overweight male volunteers ²⁵. Treatment group with 18 subjects received 1176mg daily dose of hydroalcohol extract of fenugreek seed for 6 weeks while the control group with 20 subjects received placebo. At the end of the study, no significant differences in fasting blood sugar and insulin were detected between the control and treatment group.

Taken together, the quality of trials with diabetic patients ranges from 0 to 3 Jadad Scale (Table 1). The Jadad scale, sometimes known as Jadad scoring or the Oxford quality scoring system, is a procedure to independently assess the methodological quality of a clinical trial. It is named after Colombian physician Alejandro Jadad-Bechara who in 1996 described a system for allocating the trial a score of between zero (very poor) and five (rigorous). Therefore, there is good scientific evidence (Level B2) suggesting that fenugreek is effective in reducing blood glucose levels in diabetic patients. The quality of trials with healthy, obese or overweight subjects ranges from 0 to 3 in the Jadad scale with majority of the trials exhibiting no hypoglycemic effect (Table 1).

In conclusion, a few small studies found that fenugreek may help lower blood sugar levels in people with diabetes (type 2 diabetes mellitus), but the evidence is weak ⁴. There is thus good scientific evidence to support that fenugreek is not effective in lowering blood glucose in healthy, obese or overweight subjects.

Table 1. Clinical Trials Evaluating the Hypoglycemic Effect of Fenugreek

Fenugreek seeds

The seeds exhibit pungent aromatic properties ²⁶; fenugreek is used as a spice in curry preparations ²⁷, to flavour food, and to stimulate appetite. It has been observed that chronic oral administration of an ethanol extract of fenugreek (10 mg/day per 300 g body weight) increases food intake in rats, possibly due to the aromatic properties of the seeds ²⁸. Fenugreek seeds are used in India, Egypt, and Yemen as a condiment and supplement in food, and its green leaves are widely consumed in India ²⁹. The seeds are a good source of protein, but they also contain unavailable carbohydrates, mucilages, and saponins ³⁰, ³¹. Three steroidal sapogenins (diosgenin, gitogenin, and tigogenin) were reported by Anis and Aminuddin ³², and 10 different sapogenins have been identified by analytical methods including coupled GC–MS ³³. The biological properties of fenugreek saponins have been assessed ³⁴ and they include hypocholesterolemic and antifungal activity as well as enhancement of food intake and feeding behaviour in rats ³⁵. Among other alkaloids, trigonelline is found in the seeds ³⁶. The seed contains a greater amount of minerals (Ca, P, Fe, Zn, and Mn) than other legumes ³⁷. The lipid content of the seed (neutral lipids, glycolipids, and phospholipids) is approximately 7.5% ³⁸. The aromatic constituents of fenugreek seeds include n-alkanes, sesquiterpenes, and oxygenated compounds such as hexanol and γ-nonalactone ³⁹. The seeds also contain flavonoids, carotenoids, coumarins, and other components ⁴⁰. The amino acid content is high in arginine, alanine, and glycine, but not in lysine ⁴¹; however, the nonprotein amino acid 4-hydroxyisoleucine (4-OHIle) is abundant in the seeds ⁴².

Fenugreek seed contains 30% soluble fibre and 20% insoluble fibre, which can slow the rate of postprandial glucose absorption, possibly as a secondary mechanism for the hypoglycaemic effect. Doses ranging from 2.5 g to 15 g daily of crushed and defatted seeds have been used in clinical studies (crushing allows for the release of the viscous gel fibre that contributes to fenugreek’s efficacy), while the seeds have been used in the range of 1–3 g mixed with food. Diarrhoea and flatulence are the most common side effects observed, and the fibre can affect absorption of oral medications. As one of the major effects of fenugreek is decreased blood glucose, careful monitoring of glucose levels is needed when it is taken concomitantly with insulin or other glucose-lowering agents. Fenugreek can also exhibit anticoagulant activity; therefore, it should be used under close medical supervision when anticoagulant agents are prescribed ⁴³, ⁴⁴, ⁴⁵. A decrease of serum triglycerides (TGs), total cholesterol, and low-density lipoprotein cholesterol (LDL-C) is observed with fenugreek seed administration. This may be due to the presence of sapogenins, which increase biliary cholesterol excretion, resulting in reduced serum cholesterol levels ⁴⁶. The U.S. Food and Drug Administration, with regard to food ingredients, has determined that fenugreek seed extracts are not genotoxic (based on a minimum content of 40% nonprotein amino acid 4-hydroxyisoleucine [4-OHIle]) ⁴⁷.

Amino acid 4-hydroxyisoleucine [4-OHIle] is a branched-chain amino acid only present in plants. It is particularly abundant in fenugreek seeds (0.015%–0.4%) ⁴⁸. It is synthesised from isoleucine and has been postulated as one of the molecules responsible for the antidiabetic effects in animals because of its ability to regulate pancreatic insulin secretion ⁴⁹, hence it has significant potential for the treatment of insulin resistance and diabetes ⁵⁰. The antidiabetic properties of amino acid 4-hydroxyisoleucine [4-OHIle] are related to its ability to stimulate insulin secretion, as observed in human pancreatic islet cells, in isolated perfused rat pancreas ⁴² and in in vivo studies ⁵¹. An improvement in glucose and insulin tolerance, insulin secretion, and reduced hyperglycaemia were observed in diabetic rats and dogs. Amino acid 4-hydroxyisoleucine [4-OHIle] functioned as an insulin secretagogue, but only in the presence of elevated blood glucose concentrations, in a range of 8.3–16.7 mM ⁴⁵. Due to the fact that amino acid 4-hydroxyisoleucine [4-OHIle] acts as an insulin secretagogue in the presence of elevated blood glucose concentrations, it has been proposed for the potential treatment of insulin resistance, diabetes and obesity. The beneficial effects observed are related to the regulation of blood glucose, plasma triglycerides, total cholesterol, free fatty acid levels, and the improvement of liver function. The mechanism of action is related to increased Akt phosphorylation and reduced activation of Jun N-terminal kinase (JNK)1/2, extracellular signal-regulated kinase (ERK)1/2, p38 mitogen-activated protein kinase (MAPK), and nuclear factor (NF)-κB ⁵².

The hypocholesterolemic and antioxidant activities of various extracts (water, methanol, ethyl acetate, hexane, dichloro-methane) of fenugreek seeds were investigated in cholesterol-fed rats ⁵³. Only the ethyl acetate extract reduced total cholesterol, triglycerides, and low-density lipoprotein cholesterol (LDL-C) and increased high-density lipoprotein cholesterol (HDL-C) compared with those of rats fed a cholesterol-rich diet. The phenolic and flavonoïd contents were highest in the methanol and the ethyl acetate extracts. These results showed that the ethyl acetate extract of the fenugreek seeds had a significant hypocholesterolemic effect and antioxidant activity in cholesterol-fed rats, whether this is partly due to the presence of flavonoïds in the extract needs further study ⁵³.

Fenugreek has shown to be a useful remedy in combating abnormal cholesterol profiles in hyperlipidemic populations. A daily dose of fenugreek seed administered to rats (100 or 500 mg/kg) for eight weeks lowered LDL, VLDL triglyceride and total cholesterol and increased HDL when compared to a control group ⁵⁴. Fasting cholesterol and triglyceride levels were similar across groups when fed either a high-cholesterol diet with fenugreek extract or a standard diet ⁵⁵, and post-prandial triglyceride levels were higher in rats on the standard diet ⁵⁵ concluding that fenugreek reduces triglyceride levels in fasting and post-prandial states in rats.

The mechanisms by which fenugreek may lower blood glucose levels have not been well established in humans. Acute hypoglycemic effects of fenugreek seeds and its extract have been evaluated in individuals with and without diabetes ⁵⁶, ⁵⁷, ⁵⁸. Whole fenugreek raw seeds, extracted seed powder, cooked seeds (25 g) and gum isolate of seeds (5 g) decreased postprandial glucose levels, whereas degummed seeds (25 g) showed little effect ⁵⁶. These findings suggest that acute effects of fenugreek seeds are mainly due to the gum fraction, but do not exclude a longer term effect of other fenugreek components on glycemia. Animal studies also indicate that the soluble fiber fraction of fenugreek seeds reduces the rate of enzymatic digestion and the absorption of glucose from the gastrointestinal tract ⁵⁹. However, data from other studies suggest an effect of other fenugreek components on glucose homeostasis. In diabetic rats, trigonelline ingestion increased insulin sensitivity and reduced blood glucose levels ⁶⁰. In addition, a novel amino acid derivative extracted from fenugreek seeds, amino acid 4-hydroxyisoleucine [4-OHIle], stimulated glucose-dependent insulin release in isolated rat and human pancreatic islet cells ⁶¹. In a trial of acute effects in healthy volunteers, trigonelline reduced the early glucose response during an oral glucose tolerance test ⁶². This systematic review and meta-analysis ⁶³ suggest that fenugreek seeds may contribute to better glycemic control in persons with diabetes mellitus with a similar magnitude of effect as intensive lifestyle ⁶⁴ or other pharmaceutical treatment added to standard treatment ⁶⁵.

There is also evidence linking fenugreek to reduced hepatic cholesterol levels and elevated hepatic triglyceride lipase activity ⁶⁶, the enzyme accountable for catabolizing chylomicrons and VLDL’s to smaller remnant particles ⁶⁷. Mitigation of hepatic steatosis by reducing triglyceride accumulation in the liver ⁶⁸ and prevention of ethanol-induced toxicity and apoptosis in liver cells ⁶⁹ are other recent discoveries attributable to fenugreek. An aqueous herbal extract containing fenugreek lowered alanine aminotransferase (ALT), aspartate aminotransferase (AST), and glucose values, signifying a reduction in inflammation and a feasible protective agent against alloxan-induced oxidative stress and diabetes ⁷⁰.

Table 2. Fenugreek seed nutritional facts

Fenugreek for breastfeeding

Fenugreek, has been widely cultivated in Asia, Africa and Mediterranean countries for the edible and medicinal values of its seeds. Breast milk is considered the optimal food source for newborns through 1 year of age. Many factors influence overall maternal production, including maternal pain, illness, balance of time when returning to work, anxiety, or emotional stress. Fenugreek, and milk thistle have shown mixed results in improving milk production; however, the trials were small and had a variety of limitations ⁷².

Some studies suggest ⁷, ⁸ —but haven’t proven—that fenugreek may increase milk production in women who are breastfeeding ⁹, ¹⁰.

Fenugreek side effects

Side effects of oral fenugreek are minor and include gastrointestinal upset, nausea, diarrhea, bloating, flatulence, and allergic reactions with facial edema, wheezing, dizziness and shock.

Despite being widely used, fenugreek has not been implicated in cases of clinically apparent liver injury and, in prospective studies, has had no effect on serum enzyme levels. In vitro studies have demonstrated hepatoprotective activity of fenugreek extracts in several animal models. Fenugreek can also exhibit anticoagulant activity; therefore, it should be used under close medical supervision when anticoagulant agents are prescribed ⁴³, ⁴⁴, ⁴⁵. Because of the high fiber content, estrogenic and coumadin-like effects of fenugreek, it has a potential to cause herb-drug interactions particularly if taken in high doses with antiplatelet drugs and warfarin.

What Do We Know About Fenugreek Safety ?

• Do not take fenugreek while pregnant because it may affect uterine contractions.
• Fenugreek may act like estrogen in the body and be unsafe for women with hormone-sensitive cancers. Earlier reports show that fenugreek seeds provide a mastogenic effect resulting in enhanced breast size. This study provided the evidence for estrogenic activities on breast cancer cells of fenugreek seeds ¹⁰.
• Side effects of fenugreek may include diarrhea; a maple-like smell to urine, breast milk, and perspiration; and a worsening of asthma.
• There’s little information on the risks of taking fenugreek while breastfeeding.
• Fenugreek should not be used in place of conventional medical care or to delay seeking care if you have health problems. This is particularly true if you have diabetes.

Summary

In humans, fenugreek seeds acutely reduced postprandial glucose and insulin levels ⁷³, ⁷⁴. In addition, several longer-term clinical trials showed reductions in fasting and post-prandial glucose levels and glycated haemoglobin (HbA1c) ⁷⁵, ⁵⁷, ⁷⁶, but some trials did not show benefit ⁷⁷, ⁷⁸. Systematic reviews that have evaluated the effect of various alternative therapies for diabetes included only a few clinical trials of fenugreek ⁷⁹, ⁸⁰, ⁸¹. The mechanisms by which fenugreek may lower blood glucose levels have not been well established in humans. In this meta-analysis ⁶³ of 10 clinical trials a significant reduction in glucose parameters for trials that administered medium to high doses (≥5 g) of fenugreek seed powder and not for trials that administered low doses (< 2 g) of hydro-alcoholic extracts. Medium to high doses (range: 5–25 g) of fenugreek seed powder also lowered postprandial glucose levels in acute studies ⁸², ⁸³. None of the trials reported the methods of randomization or allocation concealment, and only a few trials provided information on blinding status and drop-out rates. In addition, with some exceptions ⁷⁵ it was unclear whether other diabetes medication remained constant during the trial. Whole fenugreek raw seeds, extracted seed powder, cooked seeds (25 g) and gum isolate of seeds (5 g) decreased postprandial glucose levels, whereas degummed seeds (25 g) showed little effect ⁵⁶. A systematic review and meta-analysis suggest that fenugreek seeds may contribute to better glycemic control in persons with diabetes mellitus with a similar magnitude of effect as intensive lifestyle ⁸⁴ or other pharmaceutical treatment added to standard treatment ⁸⁵.

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