Why go only part of the way with curcumin, when … ?

Whole turmeric prevents
and treats many diseases

Human clinical trials are shedding
light on the efficacy of turmeric

By Will Block

T

urmeric has been used in Indian religious ceremonies for thousands of years. It’s a common belief among Hindus and Jainists that turmeric improves fertility. It is also considered a symbol of purity and prosperity. During religious rituals, turmeric mixed in water is poured onto statues of their gods and goddesses.

In Jainism, an Indian religion that prescribes a path of non-violence towards all living beings, its philosophy and practice emphasize the necessity of self-effort to move the soul toward divine consciousness and liberation. In a once every 12-years ritual, turmeric liquid is poured over the statue of Buhubali (see graphic) who according to Digambara (one of the two main sects of Jainism) was the first human in this “half-time cycle” to attain liberation. How symbolic, given what we know about turmeric … he was liberated from the cycle of pain and suffering.

The safety and efficacy of turmeric as medicine

Turmeric is a potent part of Ayurvedic medicine, to which Jainists have also contributed. This gold-colored spice, derived from the rhizome of the plant Curcuma longa L., has traditionally been used in India for the treatment of numerous diseases. Turmeric is a rich source of numerous biologically active constituents such as polyphenols, sesquiterpenes, diterpenes, triterpenoids, sterols, and alkaloids. Happily, modern science has delineated the molecular basis for the pharmacological properties and use of turmeric against disease. In fact, a growing number of clinical trials have unequivocally demonstrated the efficacy and safety of turmeric in human subjects.

Yet, only one of its many biologically active components has been celebrated in the West. That’s curcumin, which while constituting just 2–5% of turmeric, is turmeric’s most-studied component. Although some of the activities of turmeric can be mimicked by curcumin, other activities are curcumin-independent. Cell-based studies have demonstrated the potential of turmeric as an antimicrobial, insecticidal, larvicidal, antimutagenic, radioprotector, and anticancer agent. Numerous animal studies have shown the potential of this spice against proinflammatory diseases, cancer, neurodegenerative diseases, depression, diabetes, obesity, and atherosclerosis. Also, at the molecular level, this spice has been shown to modulate numerous cell-signaling pathways.

A new review tracks the scientific justification for turmeric

And in clinical trials, turmeric has shown efficacy against numerous human ailments, including lupus nephritis, cancer, diabetes, irritable bowel syndrome, acne, and fibrosis. Thus, a cooking spice common in the Western world is now exhibiting activities in the clinic. In a new review, conducted at The University of Texas MD Anderson Cancer Center, Houston, TX, researchers discuss the chemical constituents of turmeric, its biological activities, its molecular targets, and its potential in the clinic.1 [All references omitted.]

Chemical composition of turmeric

Turmeric is chemically diverse in composition. The qualitative and quantitative compositions of turmeric vary often with varieties, locations, sources, and cultivation conditions. To date, around 235 compounds, primarily phenolic compounds and terpenoids, have been identified from this spice. Of these compounds, 22 are diarylheptanoids and diarylpentanoids, 8 phenylpropene and other phenolic compounds, 68 monoterpenes, 109 sesquiterpenes, 5 diterpenes, 3 triterpenoids, 4 sterols, 2 alkaloids, and 14 other compounds.

The curcuminoids belonging to the group of diarylheptanoids are some of the major bioactive ingredients of turmeric. The most common curcuminoid present in turmeric is curcumin. Commercial curcumin is usually a mixture of three curcuminoids: curcumin (71.5%), demethoxycurcumin (19.4%), and bisdemethoxycurcumin (9.1%). Three diarylpentanoids with a five-carbon chain between two phenyl groups have also been identified from turmeric. Calebin-A, vanillic acid, and vanillin are other phenylpropene and phenolic compounds identified from turmeric. The essential oils from leaves and flowers are usually dominated by monoterpenes. The most common monoterpenes present in turmeric are p-cymene, β-phellandrene, terpinolene (terpenoline), p-cymen-8-ol, cineole, and myrcene. Dried turmeric rhizomes usually yield 1.5–5% essential oils, which are dominated by sesquiterpenes and are responsible for its aromatic taste and smell. The most common sesquiterpenes identified from turmeric are α-turmerone, β-turmerone, turmeronol A, and turmeronol B.

Preclinical studies with turmeric

Extensive research from both in vitro and animal models over the past several years has revealed the activities of turmeric against numerous ailments. Following is the evidence from in vitro and animal models for the biological activities of turmeric.

Cell-based studies

Antimicrobial activity

Turmeric has been shown to inhibit the growth of numerous microorganisms, including bacteria, viruses, and fungi. For instance, turmeric was shown to inhibit the growth of Helicobacter pylori, which is associated with the development of ulcers, along with gastric and colon cancers. In a few cases, turmeric has been shown to act as a preservative by retarding microbial growth. At a 5% concentration, turmeric exhibited antimicrobial activity against histamine-producing bacteria. Turmeric extract has also shown activity against food-borne pathogens. The bactericidal activities of turmeric against a Escherichia coli strain were reported by another study.

Turmeric possesses antiviral activity. In one study, the spice inhibited hepatitis B virus replication in liver cells by enhancing the level of p53 protein. Turmeric exhibits antifungal activity against numerous strains of fungus. This spice can also inhibit aflatoxin, a deadly toxin from a fungus common to peanuts.

Insecticidal and larvicidal activity

Turmeric is known to have insecticidal and larvicidal activities. For instance, turmeric was show to possess insecticidal activity against the maize weevil and the red flour beetle in one study. In another study, turmeric extract demonstrated larvicidal activity against the dengue vector of the yellow fever mosquito. The larvicidal activity of turmeric against two other mosquito larvae was demonstrated by yet another study. Turmeric exhibits toxicity against red spider mites as well.

Antioxidant activity

Turmeric acts as a free radical scavenger in several in vitro studies. In one study, ethanol extracts of turmeric were found to contain high antioxidant activities compared with aqueous extracts. In a renal cell line, turmeric exhibited protection against oxidative stress induced by hydrogen peroxide. In zebrafish, turmeric extract exhibits hypolipidemic and antioxidant activities.

Antimutagenic activity

Turmeric has been shown to inhibit mutagenicity induced by chemical mutagens. One study investigated the protective effects of aqueous turmeric extract and one that was curcumin-free against mutagenicity in bacterial strains. Both extracts exhibited anti-mutagenicity activities against bacteria. In another study, turmeric as a component of one formulation had anti-mutagenic activity against various environmental mutagens in vitro.

Growth inhibitory effects

Studies over the past several years have indicated the growth inhibitory effects of turmeric against numerous cancer cells. Turmeric inhibited the growth of Chinese hamster ovary cells and in another study, alone and in combination with gemcitabine (a chemotherapeutic drug), inhibited the growth in two pancreatic carcinoma cell lines. Together with gemcitabine, turmeric was synergistic, with IC90 (90% inhibitory concentration) levels achieved in both pancreatic cancer cell lines at lower concentrations than for either agent alone. The synergistic effect was associated with an increased inhibitory effect of the combination on nuclear factor-kappaB (NF-κB), signal transducers, and activators of transcription 3 activities as compared with single agent.

In another study, turmeric inhibited production of lipopolysaccharide-induced tumor necrosis factor-α (TNF-α) and prostaglandin E2 (PGE2) in human leukemia cells. Turmeric also inhibited the promotion of lymphoma cells. Another study evaluated extracts of turmeric for their cyto­toxic potential against breast, nasopharyngeal, lung, cervical, and colon cancer cells, along with one noncancer human fibroblast cell line. These extracts exhibited potent cytotoxic effects against cancer cells. In another study, turmeric inhibited the proliferation of human hepato­cellular carcinoma cells that correlated with a reduction in PGE2 production. SIRT1, a protein involved in longevity and diverse metabolic diseases including cancer, was shown to be down-regulated by turmeric extract in numerous cancer types including leukemia, lymphoma, and myeloma, along with other cancer types.

Radioprotector

In a few cases, turmeric was found to offer protection against damage induced by radiation, specifically gamma radiation. The spice was also found to reduce the degradation of a plasmid induced by radiation. In another study, turmeric protected against X-ray-induced DNA damage of E. coli cells.

Other activities

Turmeric also exhibits numerous other activities in in vitro studies. In one study, turmeric exhibited chemoprotective activity against induced-chromosomal damage in human lymphocytes. In another study, induced nephrotoxicity was reversed by turmeric treatment. The ethanolic extract from turmeric was shown to possess anti-psoriatic activity in a keratinocyte cell line. Psoriasis is an autoimmune disease that affects the skin.

At the molecular level, the extract decreased the expression of colony stimulating factor (CSF)-1, interleukin (IL)-8, NF-κB1, and NF-κB2. Within in vitro tissue culture conditions, turmeric possesses insulin-releasing actions. Turmeric also inhibits human pancreatic amylase activity and exhibits immune-stimulatory activities in human peripheral blood mononuclear cells.

Animal-based studies

Anti-inflammatory activity

Chronic inflammation has been associated with numerous human chronic diseases, including cardiovascular, pulmonary, autoimmune, and degenerative diseases, cancer, and diabetes. Research has indicated that turmeric can act as an anti-inflammatory agent by modulating the expression of inflammatory molecules.

For instance, turmeric was shown to possess anti­inflammatory activity during both N-nitrosodimethyl­amine administration and against a parasite infection in hamsters. Turmeric reduced the aggregation of inflammatory cells in the liver bile ducts, which correlated with a decrease in serum alanine transaminase level (a measure of liver health).

One study evaluated its effects against acute pancreatitis and pancreatitis-associated lung injury in mice. Turmeric ameliorated the severity of these conditions. It also possesses anti-inflammatory activities against induced-ear vasodilation in mice, as well as induced-paw edema in rats. Also in rats, turmeric exhibited protective effects against D-galactosamine-induced hepatitis in rats. D-galactosamine is a liver-damaging agent.

Anticancer activity

Turmeric has been most widely investigated for its anticancer activity, where it has shown potential in the liver, breast, mouth, and stomach. One study investigating hepatocarcinogenesis in rats receiving 1 or 5% turmeric before, during, and after carcinogen exposure showed a significant decrease in the incidence of focal dysplasia and hepatocellular carcinomas.

These studies suggested that turmeric has chemopreventive activities against hepatocarcinogenesis in rats. Some other studies have also shown the potential of turmeric against liver carcinogenesis. Another study investigated the modulating effects of turmeric and curcumin-free aqueous turmeric extract on induced mammary tumorigenesis in rats. Dietary administration of turmeric was associated with a significant suppression of induced-mammary tumorigenesis.


SIRT1, a protein involved in longevity
and diverse metabolic diseases
including cancer, was down-regulated
by turmeric extract in numerous
cancer types, including leukemia,
lymphoma, and myeloma, along with
other cancer types.


Turmeric also exhibited activity against oral carcinogenesis leading to a decrease in tumor burden and number during hamster cheek pouch tumorigenesis. Turmeric also diminished the mRNA expression of proto-oncogenes. The tumor retardation effects of turmeric against cheek pouch tumors in Syrian golden hamsters have also been investigated. Tumor number and tumor burden were significantly lower in the animals receiving turmeric. The study demonstrated the chemopreventive potential of turmeric against oral precancerous lesions.

Activity against neurodegenerative diseases

The most common neurodegenerative diseases in which turmeric has shown potential are Parkinson’s disease, Alzheimer’s disease, and arthritis. Multiple pathways including oxidative stress and mitochondrial damage have been implicated in neurodegeneration during Parkinson’s disease. One study evaluated the neuroprotective property of turmeric in neurodegenerated mice and found turmeric to protect the mouse brain against neurotoxic insults. Beta amyloid (Aβ) aggregation and tau phosphorylation are characteristic features of Alzheimer’s disease. When Aβ protein was overexpressed in mice, turmeric significantly reduced Aβ aggregation, tau phosphorylation, and plaque burden.

Arthritis is a chronic inflammatory and destructive joint disease affecting 1% of the adult population worldwide. In rats with arthritis, oral administration of turmeric extract was shown to arrest the degenerative changes in the bones and joints of the rats. The antiarthritic efficacy and mechanism of turmeric’s effects on rheumatoid arthritis were profoundly shown in one study, namely joint inflammation and periarticular joint destruction in a dose-dependent manner. The extract also prevented local activation of NF-κB and the expression of NF-κB-regulated genes including chemokines, cyclooxygenase-2, and receptor activator of nuclear factor kappa-B ligand.

Antidepressant activity

Depression is a mental disorder that affects a person’s mood, thoughts, feelings, behavior, and overall health. The major antidepressants produce a plethora of associated side effects. One study to determine the behavioral, neurochemical, and neuroendocrine effects of ethanolic turmeric extract found that turmeric reduced the duration of immobility of mice in a swimming test. The extract markedly reduced swim stress-induced decreases in serotonin, 5-hydroxy indoleacetic acid, noradrenaline, and dopamine concentrations. The extract also significantly reversed the swim stress-induced increases in serum corticotropin-releasing factor and cortisol levels.

Antiaging skin activity

The most common symptoms of aging skin are changes in skin thickness, elasticity, pigmentation, and wrinkling. Turmeric operated against long-term, low-dose ultraviolet B (UVB) irradiation in melanin-possessing hairless mice. It prevented an increase in skin thickness and a reduction in skin elasticity induced by chronic UVB exposure. The extract also prevented the formation of wrinkles and melanin as well as increases in the diameter and length of skin blood vessels.

Antidiabetic and anticataract activity

Turmeric has shown potential against diabetes and in a mouse study showed promise for the prevention and/or amelioration of type 2 diabetes. Another study examined the modulatory effects of turmeric against diabetes and oxidative stress and found that turmeric significantly alleviated (80–97%) the signs of diabetes (hyperglycemia and dyslipidemia) by increasing the production of insulin, enhancing the antioxidant defense system, and decreasing lipid peroxidation.

Turmeric was also effective against the development of cataracts in diabetic rats. Another study evaluated the efficacy of turmeric against induced-diabetes mellitus in a rat model. The result was a reduction in blood sugar and glycosylated hemoglobin levels. Turmeric also reduced the levels of oxidative stress in the rats.


Turmeric acts as a memory enhancer
and as an antiplatelet agent.


Wound healing

Turmeric, as a component of a polyherbal preparation, has been shown to increase the cellular proliferation and collagen synthesis at wound sites in normal rats. The turmeric formulation also increased the DNA, total protein, hydroxyproline, and hexosamine contents at the wound site. The efficacy of a fresh turmeric paste to heal wounds has also been demonstrated in a rabbit model.

Protection from chemical insults

Turmeric has been shown to protect normal cells, tissues, and organs against the damage caused by external insults. Turmeric has also been shown to protect against liver oxidative damage and genotoxicity induced by lead acetate in mice and to reduce arsenic toxicity in mice.

Fluoride is toxic to neuronal development. One study demonstrated the efficacy of turmeric against fluoride toxicity in rat pups. Turmeric also showed protective effects against induced-liver damage in rats. In another study, the protective effects of turmeric against induced hepatotoxicity in rats were associated with an increase in the activities of antioxidants and phase II detoxifying enzymes. Turmeric has also been shown to suppress cardiac, hepatic, and renal toxicities in rats.

Antiatherosclerotic activity

Atherosclerosis is characterized by oxidative damage that affects lipoproteins, the walls of blood vessels, and subcellular membranes. The oxidation of LDL also plays an important role in the development of atherosclerosis. In one study, turmeric decreased the susceptibility of liver microsomes and mitochondria to lipid peroxidation in atherosclerotic rabbits. In another study, turmeric extract inhibited LDL oxidation and had hypocholesterolemic effects in atherosclerotic rabbits.

Other activities, including memory enhancement

In addition to the activities indicated above, turmeric acts as a memory enhancer and as an antiplatelet agent. Turmeric supplementation in rats fed a high-cholesterol diet was associated with decreases in total plasma cholesterol and LDL cholesterol and an increase in HDL cholesterol, as well as several other variables associated with hypercholesterolemia. Turmeric also reduces the risk of infections caused by impaired neutrophil functions in sheep.

Human studies

Turmeric has been tested in human subjects, with about a dozen trials completed to date. The most promising effects of turmeric have been observed against inflammatory conditions, cancer, diabetes, irritable bowel syndrome (IBS), acne, and fibrosis. The poor bioavailability of curcumin, one of the potent constituents of turmeric, appears to be primarily due to poor absorption, rapid metabolism, and rapid systemic elimination. One study demonstrated that turmeric extract can be administered safely to patients with colorectal cancer at doses of up to 2.2 g daily, containing the equivalent of 180 mg of curcumin. However, curcumin by itself was found to have low oral bioavailability due to intestinal metabolism. Other promising approaches to increase the bioavailability of curcumin include use of nanoparticles, liposomes, micelles, phospholipid complexes, and structural analogues. But whole turmeric is valid as well.


Other promising approaches to
increase the bioavailability of
curcumin include use of
nanoparticles, liposomes, micelles,
phospholipid complexes, and
structural analogues.


One Indian study compared the use of a 2% whole turmeric gel as an adjunct to periodontal scaling and root planing to the effects observed using root planing alone. Subjects receiving the root planing along with the gel for 7 days demonstrated statistically significant reductions in the biomarkers of periodontitis.

Lupus nephritis is an autoimmune disease characterized by polyclonal B-cell hyperactivity and defective T-cell function. While responsive to immunosuppressive and steroid therapy, sometimes the disease relapses. In a gold-standard study, the effect of oral turmeric on 24 patients with lupus nephritis was investigated. Each patient in the trial group received one capsule containing 500 mg of turmeric with each meal for 3 months, after which, compared to controls, a significant decrease in proteinuria was observed in the trial group group. Also, systolic blood pressure and hematuria were significantly lower in the trial. The authors concluded that short-term turmeric supplementation can safely decrease proteinuria, hematuria, and systolic blood pressure in patients with relapsing or refractory lupus.

Turmeric has also exhibited anticancer activity in human subjects. Increased levels of nitric oxide (NO) have been reported in different leukemias. One study evaluated the effects of turmeric powder in reducing NO levels in 50 leukemia patients comparing the anti-leukemia drug imatinib (400 mg twice a day) to imatinib (400 mg twice a day) along with turmeric powder (5 g three times/day) for 6 weeks. Nitric oxide levels were significantly decreased in both the groups, although the decrease was more prominent in the group also taking turmeric.

The ethanol extract of turmeric was found to produce remarkable symptomatic relief in patients with external cancerous lesions in another study. One study evaluated the effects of turmeric filled capsules in 45 patients with peptic ulcers. Each was given 300 mg of turmeric orally at a dose of two capsules, five times daily. Twenty-five of these underwent endoscopy for their ulcers, located in the duodenal bulb and gastric tract. The result showed that ulcers were absent in 12 patients (48%). Eighteen patients had no ulcers after 8 weeks of treatment and 19 did not have ulcers after 12 weeks of treatment. The remaining 20 cases were not found to have ulcers and some did not undergo endoscopy. These subjects appeared to have erosions, gastritis, and dyspepsia; turmeric capsules were then given for 4 weeks. The abdominal pain and discomfort satisfactorily subsided in the first and second weeks. The study concluded that turmeric has the capacity to heal peptic ulcers.

End-stage renal disease due to type 2 diabetic nephropathy is a very common condition that is associated with high global levels of mortality and morbidity. Both proteinuria and transforming growth factor (TGF-α) may contribute to the development of end-stage renal disease in patients with diabetic nephropathy. One study investigated the effects of turmeric on serum and urinary TGF-α, IL-8, and TNF-α, as well as proteinuria, in patients with overt type 2 diabetic nephropathy. The study consisted of 40 patients with overt type 2 diabetic nephropathy that were randomly assigned to either the trial group (n = 20) or the control group (n = 20). Each patient in the trial group received one capsule (containing 500 mg of turmeric, three times a day) with each meal for 2 months. Serum concentrations of TGF-α and IL-8 and urinary protein excretion and IL-8 decreased significantly compared with the pre-supplementation values.


Turmeric has the capacity
to heal peptic ulcers.


Another study examined turmeric’s effects on postprandial plasma glucose and insulin levels and the glycemic index in healthy subjects. Fourteen healthy subjects were assessed in a crossover trial. The study found that turmeric increased postprandial serum insulin levels but had no effect on plasma glucose levels or the glycemic index in these healthy subjects. The study concluded that turmeric might have an effect on insulin secretion.

A partially blinded, randomized, two-dose, pilot study assessed the effects of turmeric extract on symptoms of IBS. Five hundred volunteers participated in the study. The volunteers were given one (72 mg) or two tablets (144 mg) of a standardized turmeric extract daily for 8 weeks, not a large amount. IBS prevalence decreased significantly in both the one- and two-tablet groups, and approximately two-thirds of all subjects reported an improvement in symptoms after treatment. Another study conducted with eight healthy subjects reported that turmeric has the potential to increase bowel motility and to activate hydrogen-producing bacterial flora in the colon.

One study assessed the anti-mutagenic effects of turmeric in 16 chronic smokers. Turmeric, given in doses of 1.5 g/day for 30 days, significantly reduced the urinary excretion of mutagens in smokers. Thus, the researchers concluded that turmeric is an effective antimutagen and that it may be useful in chemoprevention. In patients with submucous fibrosis, turmeric extract decreased the number of micronucleated cells both in exfoliated oral mucosal cells and in circulating lymphocytes.

In addition to the studies discussed in the above sections, numerous ongoing trials are evaluating the efficacy of turmeric in humans, including a phase II clinical trial that was aimed to determine the efficacy and the tolerance on 15 days of a turmeric extract in patients with osteoarthritis of the knee. The purpose of another phase I study is to assess the safety of advancing doses of curcuminoids administered orally for 14 consecutive days in adults with cystic fibrosis homozygous. Whether antioxidant spices including turmeric can reduce cardiovascular risks was investigated in another randomized controlled trial from the US. While these studies are completed, the results are not yet published.

Conclusions

Turmeric has long been used as a spice, flavoring agent, and colorant, and traditionally it has been used to treat numerous human ailments. Due to its richness of numerous biologically active constituents such as polyphenols, sesquiterpenes, diterpenes, triterpenoids, sterols, and alkaloids, modern science has investigated the molecular basis for the pharmacological properties of turmeric … against human diseases, and some clinical trials have unequivocally demonstrated the safety and efficacy of turmeric in human subjects.

Plus, the absence of any significant toxicity associated with turmeric has made it superior to drugs. The existing human studies, in addition to in vitro and in vivo animal studies, provide a logical basis for the use of it for the prevention and treatment of human diseases.

Reference

  1. Gupta SC, Sung B, Kim JH, Prasad S, Li S, Aggarwal BB. Multitargeting by turmeric, the golden spice: From kitchen to clinic. Mol Nutr Food Res 2012 Aug 13. doi: 10.1002/mnfr.201100741. [Epub ahead of print]


Will Block is the publisher and editorial director of Life Enhancement magazine.

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