Monographs


Curcuma longa

Phytotherapy

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Synonyms

yellow root, turmeric

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Introduction

From time immemorial, the Curcuma longa, the yellow root, has been cultivated in India, Southern China and other tropical and subtropical countries. It is conjectured that the yellow root originates from East India, but this is not certain because the plant has never been found in the wild. The plant’s flower and growth pattern looks very similar to that of ginger and it is also in the same family as ginger (Zingiberaceae). The yellow root can grow to a height of approximately 1 metre. A bundle of leaves and flower stalk with a 20-cm-long flower rises from the rootstock. Similarly to the ginger plant, side shoots with corm-like swellings develop underground. The yellow root grows best in damp and warm areas. The underground parts of the plants are dug up when the flowers wilt in December and January. The corms and the rootstock are separated from the side shoots. These are then submerged in boiling water and placed in the sun to dry. Through drying in the sunlight, the under-ground parts become yellow in colour: the heat from the sun causes the pigment from the glandular cells to be distributed over the rootstock and corms. Once they are dry, the rootstocks are ground to form a powder which is called “curcumin” or “curcuma”. The powder is then sold under the name “fumeric”.

Species

There are various species of Curcuma. In addition to Curcuma longa – the real yellow root – there is a Curcuma xanthorrhiza (Temoe Lawak, Javanese Curcuma root, bitter Curcuma root) and a Curcuma zedoaria (Zedoary root). The Dutch introduced Curcuma xanthorrhiza to Europe, where it was given the well-known name “Temoe Lawak”. The Curcuma zedoaria plant originates from the Himalayas, where the leaves are used in salads.
According to Van Hellemont, the Curcuma xanthorrhiza is preferred as, because of a higher concentration of essential oils, this species has a more powerful cholagogic and choleretic effect than the Curcuma longa. He says that the Curcuma longa is more popular in cooking and the Curcuma zedoaria should be seen as more of a stomach remedy. However, research shows that the Curcuma longa does actually have powerful cholagogic and choleretic properties in addition to numerous other pharmacological properties, which have not yet been demonstrated in the xanthorrhiza. The WHO’s monograph therefore rightly relates to the Curcuma longa and describes its effects as hepatoprotective (liver cell protection), antioxidant, inflammation inhibitor, and its antibacterial and fungicidal properties (fungicidal).

Traditional medicine

Yellow root is an important seasoning in Indian cuisine; yellow root is one of the principal ingredients of curry. Yellow root not only gives meals a beautiful, deep yellow colour (popular in rice), but its slightly bitter taste also encourages consumption.
In addition to being appreciated for its culinary uses, yellow root has also been used for a long time in the treatment of liver and bile problems, jaundice and general digestive symptoms. In addition, in traditional medicine, the plant was also used for arthritis because of its inflammation-inhibiting properties.

Curcuma is surprisingly versatile

Curcumin, the principal ingredient of the curcuma seasoning, is a likely winner of the “cure-all” title: a (wonder) remedy that can cure all ailments. In hundreds of pre-clinical studies, various health-enhancing effects of curcumin have been revealed. The number of human clinical studies using curcumin is limited; more research is required to find out whether, following oral intake, the therapeutic properties of curcumin (including the antioxidative and inflammation-inhibiting activity) can be sufficiently expressed, plus the dose required to achieve that. Curcumin is a promising phytonutrient for the prevention and treatment of a diversity of disorders, such as atherosclerosis, cataracts, rheumatoid arthritis, gall stones, stomach ulcers, inflammatory bowel diseases, depression and dementia.

Seasoning and phytotherapeutics

The root of curcuma longa (Asian yellow root, curcuma), a plant that belongs to the ginger family, is a favourite and commonly used seasoning in Eastern cuisine. It gives (curry) meals a mild bitter flavour and a deep-yellow colour. Every day, the Indian population consumes 2-2.5 grams of dried yellow root (with 60-200 mg of curcuminoids); Westerners use significantly less curcuma in their food. The monographs that the World Health Organisation and German Commission E have applied to curcuma, recommend curcuma for (functional) dyspepsia, gall bladder dysfunction (cholestasis, lithogenic bile), peptic ulcer, lack of appetite and rheumatoid arthritis [1,2]. The recommended dose is 1.5-3 grams of curcuma per day; doses up to 8 grams per day are prescribed for stomach and duodenal ulcers. It is required that the product contains a minimum of 3% curcuminoids and 4% essential oils.

Properties of curcumin  

The therapeutic properties of curcumin were determined in hundreds of in-vitro and animal studies; various reviews describe the cellular, molecular and biochemical mechanism of action of curcumin [3,5-9]. Briefly summarised: curcumin has antioxidative, inflammation-inhibiting, immunomodulating, wound-healing, lipid-lowering, detoxicating, liver protective, uncramping, neuroprotective, digestive-boosting, anti-angiogenic and antimicrobial properties [1,3-7,10-12].

In practice  

Depending on the intended effect, extensive clinical research is required in order to determine the effective (preventative, therapeutic) dose of curcumin. Curcumin has moderate biological availability following oral administration by a fast conjugation in the intestines and liver to curcumin glucuronides and sulphates or reduction to hexahydrocurcumin. Between 40 and 85% of the curcumin leaves the gastrointestinal tract with the stools [3,7,8]. For a local effect (in the gastrointestinal tract) this is fine; there are indications that orally administered curcumin accumulates in the tissues of the gastrointestinal tract. Studies have also revealed that curcumin has systemic effects at a relatively low dose; for example, a dose of 20 mg of curcumin has a significant effect on gall bladder contraction and serum lipid peroxidation. Curcumin disappears rapidly from the blood circulation, but also easily passes the blood-brain barrier and can be active there at a relatively low concentration. Insufficient is known about the biological activity of curcumin metabolites.[3,9].

Active compounds  

Essential oils (2-7%) consisting of 60% sesquiterpenes with methyl-p-tolyl carbinol, turmeron, aturmeron, atlanton and zingiberene; orange colorants such as curcumin (1.5-5.4%), monodesmethoxycurcumin (0.8%), didesmethoxycurcumin (0.5%).
Although the essential oils with mono-sesquiterpenes and sesquiterpenes most certainly contribute to the therapeutic effect of curcuma, mainly the yellow-orange curcuminoids are responsible for the healing effects of curcuma. Curcuminoids are non-volatile, fat-soluble polyphenols (dicinnamoylmethane derivatives); 75-80% thereof is curcumin (curcumin I /diferuloylmethane), the remainder comprises curcumin II (demethoxycurcumin) and curcumin III (bisdemethoxycurcumin) [3,4]. Most research now focuses on curcumin; by using curcuma extracts with a very high level of curcumin (90-95%), significantly more powerful effects can be achieved than with unprocessed curcuma (that contains 2-9% curcumin).

Mechanism of action  

The traditional medicinal uses seem to be very closely in line with the scientific research that has taken place during the past years into the plant’s mechanism of action. The main active ingredients are the curcumin and the essential oils. The monograph of the WHO and Van Hellemont indicate that cholagogic and choleretic properties of the yellow root can be attributed to the essential oils and the curcumins.
The curcumins appear to:
  • increase the secretion of bile;
  • promote the flow of bile to the intestine;
  • protect the liver (hepatoprotective effect) and support liver function;
  • raise the level of glutathione in the liver;
  • stimulate the activity of glutathione S-transferase in the liver;
  • promote the detoxification of toxic substances;
  • inhibit blood platelet aggregation;
  • possess antibiotic properties;
  • lower the cholesterol level;
  • possess antioxidative properties;
  • have a catabolic and metabolic effect on fat absorption;
  • have inflammation-inhibiting properties;
  • have a fungicidal effect on, amongst others, Candida albicans.
In the future, scientific research will elaborate on many of the aforementioned properties. Particularly the inflammation-inhibiting properties receive significant amounts of attention in the treatment of rheumatoid arthritis.
Other interesting actions are the inhibition of blood platelet aggregation and the reduction in the cholesterol level (use in cardiovascular disorders), hepatoprotective properties (use in detoxicification), choleretic and cholagogic properties (use in gallbladder function disorders and constipation) and the antibacterial and fungicidal properties.
The most commonly mentioned indications are cholelithiasis, cholecystitis, liver parenchyma damage, icterus and inflammations of the gall bladder and biliary tracts.

Indications

Antioxidant  

Curcumin is a powerful (fat-soluble) antioxidant and radical scavenger of oxygen radicals and reactive nitrogen particles. Indirectly, curcumin is responsible for an improved antioxidant defence by a rise in the activity of antioxidant enzymes (glutathione peroxidase, superoxide dismutase, catalase) and a rise in the glutathione level (the main intracellular antioxidant) by increasing the expression of genes for GCL (glutamate-cysteine ligase, the rate-limiting enzyme in the glutathione synthesis) [13,14]. Curcumin offers support in disease processes associated with lipid peroxidation such as atherosclerosis, neurodegenerative illnesses (including Alzheimer’s disease) and inflammatory diseases. Animal research demonstrated that curcumin limits ischemia-reperfusion damage in the heart and brain [3,7,9,15]. Curcumin protects the brain against damage caused by alcohol consumption, whereby a decrease in oxidative stress and lipid peroxidation and an improvement of the glutathione level in brain tissue is seen. In healthy volunteers, a low oral dose of curcumin (20 mg per day for 75 days) resulted in a significant fall in serum lipid peroxidation by 60% [17].

Pro-inflammatory eicosanoids  

Curcumin inhibits both acute and chronic inflammatory processes. First and foremost this is because curcumin counteracts the formation of pro-inflammatory eicosanoids (arachidonic acid metabolites). These powerful inflammation mediators occur when arachidonic acid is released from membrane phospholipids by phospholipase-a2. Arachidonic acid is then converted by the enzymes cOX-2 (cyclooxygenase-2) and 5-LOX (5-lipoxygenase) into type-2-prostaglandins and type 5 leucotrienes. Laboratory tests have proven that curcumin significantly inhibits the activity of the enzymes phospholipase-a2, cOX-2 and 5-LOX [3,18]. The fact that curcumin inhibits phospholipase-a2 is very favourable because cutting loose arachidonic acid from membrane phospholipids is the rate-limiting step in the production of pro-inflammatory eicosanoids. Pro-inflammatory eicosanoids not only boost typical inflammatory diseases but also neurodegenerative diseases, diabetes type 2, cardiovascular diseases, auto-immune illnesses and COPD.

Transcripton factor NF-kB  

The second equally important way in which curcumin counteracts inflammations is by inhibiting activated NF-kB (nuclear factor kappa-B) [21]. NF-kB is a group of inducible transcription factors – present in almost all of the body’s cells – which exercise control over the transcription of genes that regulate the inflammatory response by producing cytokines, chemokines, adhesion molecules, metalloproteinases and acute phase proteins. Inflammatory and immune responses are – particularly following activation by pathogenic micro-organisms – largely coordinated by NF-kB [22]. NF-kB is responsible for the increase in oxidative stress; activation of NF-kB is, amongst others, associated with asthma, contact allergy, atherosclerosis, heart failure, ischemic reperfusion, AIDS, septic shock, (rheumatoid) arthritis, sarcoidosis, COPD, diabetes, Irritable Bowel Disease (IBD) and multiple sclerosis [22-25]. Researchers suspect that an increase in NF-kB activity is one of the main causes of aging / age-related illnesses and can have an impact on life expectancy; this would mean that curcumin is an anti-aging substance [3,26,27].

Immunomodulation  

In an experimental animal study (for chronic colitis), it was recently demonstrated that curcumin has a regulatory action on the balance between th1 and th2 cells and the th1/th2 ratio shifts in the direction of th2 cells [28]. T helper cells (lymphocytes) influence the inflammation process through the type (pro-inflammatory) of cytokines (interleukins, tumour necrosis factor (tNF)) that they produce. In a healthy defence system, there is a good balance between the th1 and th2 cells.
In th2 mediated immune illnesses such as allergies, the th1/th2 ratio has shifted towards (overactivity of) th2 cells; in th1 mediated inflammations are the dominating factor of the activity of th1 cells. Curcumin can possibly have an impact on the disease process of th1 medicated immune illnesses such as auto-immune illnesses (rheumatoid arthritis, SLE, scleroderma, diabetes type 1, psoriasis, and multiple sclerosis), chronic infections, depression and atherosclerosis [3,28,29].

Post-operative inflammation

In a human pilot study it was demonstrated that curcumin combats post-operative swelling and inflammation [30]. Forty-five patients who had recently undergone groin surgery were given a placebo for five days, curcumin (1,200 mg/day) or phenylbutazone (300 mg/day). Curcumin and (to a lesser degree) phenylbutazone had a significant inflammation-inhibiting effect with a reduction in pain, sensitivity and swelling in comparison to the placebo.

Rheumatoid arthritis

Activation of NF-kB probably plays a central role in the disease process of rheumatoid arthritis [3, 22, 31]. Orally administered curcuminoids (117 mg/kg/day) significantly inhibited the acute and chronic phase of experimental rheumatoid arthritis [31]. As from the fourth day before >arthritis was induced, laboratory animals were given curcumin. This resulted in 48% inhibition of the acute inflammation process and 45% inhibition of the chronic degenerative process. The dose of curcuminoids given is comparable to a dose of one gram per day for people weighing 70 kg. Curcumin supplementation had much less of an effect when it was given just eight days after inducing arthritis (in the acute phase). In a small double-blind study, 18 people with rheumatoid arthritis were given curcumin for a two-week period (1,200 mg per day) or an NSAID (300 mg of phenylbutazone per day) [1, 4]. Both curcumin and phenylbutazone significantly reduce morning stiffness and joint swelling and improved walking.

Inflammatory intestinal disorder

Curcumin was tested in an animal model for inflammatory intestinal disorders (Crohn’s disease, ulcerative colitis) [32]. The diet of mice suffering from colitis contained 0.5, 2 or 5% curcumin. Supplementation with curcumin resulted in suppression of NF-kB with a decrease in proinflammatory cytokines (IL-1 beta, IL-6, tNF alpha, IL-12 and interferon gamma) and a reduction in clinical and histological signs of mucous membrane inflammation in the large intestine. The study revealed for the first time that treatment with curcumin relieved experimental colitis in mice and can prevent undernourishment and death. Curcumin (72-144 mg per day) potentially also works in irritable bowel syndrome (spastic colon) [33]. A non-placebo-controlled pilot study involving 207 people with a spastic colon showed an improvement after eight weeks of stomach ache, defecation pattern and quality of life.

Depression  

In Chinese medicine, curcuma is the main ingredient of the herbal formula against depression. Curcumin is fat-soluble and can effortlessly pass the blood-brain barrier. In animal models for depression it has been proven that curcumin at an oral dose of 5 and 10 mg/ kg/day can significantly reduce depressive behaviour [34]. Curcumin inhibits the enzyme monoamine oxidase (MAO) and increases the activity of serotonin, noradrenaline and dopamine in the brain. The dose of 10 mg/kg/day resulted in a significant rise in the serotonin and noradrenaline levels in the frontal cortex and hippocampus, as well as in the dopamine level in the frontal cortex and striatum. These brain areas are important for emotion, motivation, learning and memory.

Infections

Curcuma has a broad antimicrobial activity and inhibits (in-vitro) the growth of gram-positive bacteria (Staphylococcus aureus), viruses (HIV, human papillomavirus), pathogenic fungi, protozoa (Leishmania, giardia lamblia, trichomonas vaginalis, plasmodium) and worms [1, 3, 5-7, 9-11, 35-39]. It is of importance that curcuma extract (in-vitro) inhibits the MRSA bacteria (Multiresistant Staphylococcus aureus) and resensitises this to beta lactam antibiotics [40]. In-vitro it has been proven that, at a low concentration, the essential oils of curcuma inhibit gram-positive bacteria such as Staphylococcus aureus and that this effect is equal to that achieved by ampicillin, doxycycline and gentamicin [39].

Wound healing

In India, an externally applied paste made from curcuma is a tried and tested home remedy for wounds. Research has confirmed that curcumin aids wound healing; it stimulates the migration of macrophages, neutrophils and fibroblasts to the wound, accelerates the wound contraction, stimulates the formation of granulation tissue, supports the formation of new blood vessels (neovascularisation) and improves re-epithelialisation [3,7,41,42]. Curcumin also accelerates the recovery of wounds that have difficulty healing on account of inflammation, diabetes, the use of hydrocortisone or radiation [6,7,9,42]. An additional benefit is that curcuma helps to prevent wound infection.

Psoriasis

In a study involving forty psoriasis patients, it was proven that a gel containing 1% curcumin favourably affected the th1 mediated inflammation process in the skin [43]. In this hyperproliferative inflammatory illness, large numbers of dividing keratinocytes migrate too quickly towards the skin surface. An increased activity of the phosphorylase kinase enzyme plays a central role in this; this signal molecule regulates the cell division and cell migration. In the study, it was proven that curcumin is better at counteracting the rise of the phosphorylase activity than calcipotriol.

Stomach ulcer

Curcuma reduces pain and accelerates the healing of stomach and duodenal ulcers. Apart from the antioxidative and inflammation-inhibiting action, curcuma is responsible for an improved protective mucous layer [1,9,44,45]. In addition, curcuma is a natural gastric acid inhibitor: it reduces (histamine-induced) gastric acid secretion by means of dose-dependent competitive binding to h2 histamine receptors; it is not yet clear which components are responsible for this effect [46]. Curcuma and curcumin (in-vitro) also inhibit the growth and attachment of the bacteria helicobacter pylori, the bacteria which causes stomach ulcers. Curcumin combats stomach ulcers caused by stress, alcohol, reserpine and NSAIDs [9,45]. During animal testing in which stomach ulcers were induced by indomethacin, curcumin was responsible for dose-dependent protection of the gastric mucosa; 60 mg of curcumin per kilogram of body weight was able to prevent 85% of the damage caused by indomethacin [45]. In a Thai study, 19 of the 25 patients with endoscopically proven peptic ulcers were cured within twelve weeks through treatment with curcumin (5x 600 mg per day) [44]. Other patients with symptoms of dyspepsia, gastritis and mucous membrane irritation also benefitted from curcumin supplementation.

Digestion, liver en bile  

Curcuma supports digestion and reduces the symptoms of dyspepsia [1,2,9]. A group of 116 test subjects used 4x500 mg of curcuma powder each day for seven days or a placebo.
Supplementation with curcuma resulted in a significant reduction in symptoms (flatulence, nausea, bloated feeling, acid reflux) [1]. In Indonesia, curcuma has been used from way back to prevent (cholesterol) gall stones. An experiment involving healthy volunteers shows that (dose-dependent) curcumin stimulates gall bladder contraction and the release of bile and can be useful as a cholekinetic substance [48]. In twelve test subjects who took 20, 40 or 80 mg of curcumin on an empty stomach, after two hours, the gall bladder volume has reduced by 30, 50 and 70% respectively, observed using ultrasonography of the gall bladder. Research has also revealed that curcuma boosts the secretion of bile acids (and bilirubin) and improves the bile composition, on account of which the cholesterol in bile is more likely to remain in solution and does not settle as quickly [9]. Mice that received a gallstone-promoting food for ten weeks which contained 0.5% curcumin, had 75% fewer gall stones compared to the control group; additionally, the cholesterol level in the bile dropped significantly [3]. Curcuma and curcumin protect the liver and in animal testing counteracted liver damage by ethanol, ccl4 (tetrachlorocarbon), galactosamine, paracetamol and aspergillus aflatoxin.

Atherosclerosis  

Curcumin inhibits atherosclerosis; this has been proven in animal testing [3,50-52]. This is through the inhibition of lipid peroxidation, improvement of the vessel endothelial function, inhibition of smooth muscle cell proliferation in the vascular wall and improved vasodilatation; curcumin reduces the LDL cholesterol and triglyceride level, improves the HDL cholesterol level, inhibits LDL oxidation, inhibits platelet aggregation, reduces a too-high fibrinogen level and improves the ratio between (unfavourable) apolipoprotein B (apoB) and (favourable) apoA [3,50-55]. In various human pilot studies, it has been proven that curcumin reduces lipid peroxidation and is good for the blood lipids and fibrinogen level [3,52,55,56]. Significant effects are already seen upwards of a dose of 20 mg of curcumin per day [52]. During a pilot study, ten healthy adults took 500 mg of curcumin per day for a week; the total cholesterol level dropped (on average) by 12%, the level of serum lipid peroxides by 33%, the HDL level rose by 29% [3].

Asthma  

In an animal model for asthma, the effectiveness of curcumin was tested in the sensibilisation phase and in airways symptoms that were present [57].Orally administered curcumin (20 mg/kg/day) relieved significant ovalbumin-induced (acute) airway narrowing and (late) hyperreactivity of the airways (for histamine). Curcumin has an inflammation-inhibiting and cramp-reducing activity and inhibits the IgE-dependent release of inflammatory mediators from mast cells (histamine, leucotrienes).

Alzheimer’s disease  

Alzheimer’s disease is characterised by peptide aggregation (amyloid beta or a-beta) in the brain, which is associated with plaque formation, inflammation and oxidative stress. Alzheimer’s disease is less common in people with a higher intake of antioxidants and (natural) inflammation inhibitors [12,58]. Various in-vitro and animal studies suggest that curcumin helps in the prevention and treatment of dementia. A low concentration of curcumin, added to the feed of older mice, inhibits the deposit of a- beta in the brain and counteracts oxidative stress, inflammation and cognitive deterioration through plaque formation; therefore it deals with both the cause and the consequence [12,59,60]. Curcumin potentially also aids the breakdown of plaques: curcumin is also responsible for the destabilisation of coagulated a-beta and is more proficient at this than ibuprofen and naproxen.
In-vivo studies show that peripherally injected curcumin passes the blood-brain barrier and binds to plaques. It is still unclear whether, after having been taken orally, sufficient quantities of curcumin reach the brain. Meanwhile, (phase 2) clinical studies are underway involving people with mild to moderate dementia, whereby the effect and tolerability of doses of curcumin between 1 and 4 grams a day are being examined.

Cataracts  

Cataracts can potentially be inhibited by the use of curcumin. Rats received curcumin in their feed for a fourteen-day period (75 mg/kg/day). Subsequently, in-vitro the eye lens was exposed to a cataract-promoting substance. The eye lenses of animals that had eaten curcumin were more able to resist cataract formation by lipid peroxidation, partially through the increase in the enzyme glutathione S-transferase in the eye lens epithelium [61]. Diabetic retinopathy and glaucoma which partially occur through the activation of N-methyl-D-aspartate receptors (NMDA-receptors) in de retina through short periods of hypoxia, whereby an inflammation process occurs. Curcumin protects the eye (in-vitro) against excitotoxic cell damage through inhibition of (activated) NMDA receptors without disturbing the normal physiological function of NMDA receptors [62]. In diabetic rats, curcumin inhibited (0.01% diet) and curcuma (0.5% diet) (dose-dependent) the development of (diabetic) cataract [63].


Contra-indications

Curcumin can influence the metabolism of medicines; curcumin can boost the action of blood thinners and is (at high doses) contraindicated in large gallstones or closing of the biliary tract through gallstone blockage, obstructive icterus, acute gallstone colic and extremely toxic liver disorders. Use of the extract during pregnancy and lactation are advised against.

Side effects

Doses that are too high can give rise to irritation of the gastric mucosa and have to be avoided by patients with a stomach or intestinal ulcer. Sometimes, the use of yellow root extracts can increase the frequency of defecation.

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