TURMERIC

Turmeric (Curcuma longa) is a perennial herbaceous plant of the ginger family (Zingiberaceae). Although it has more than 300 active components, the primary biologically active component forming the basis for the medicinal properties of this plant is a material taken from its root that has the feature of being a yellow or orange pigment. This substance called curcumin, is also the main component of curry powder commonly used in Asian cuisine. It is also used as a food colorant ^[1].

Curcumin, a polyphenol, has been demonstrated to target multiple signaling molecules while also exhibit activity at the cellular level, supporting its numerous health advantages. It has been shown to benefit inflammatory conditions, metabolic syndrome, pain, and to help in the management of inflammatory ^[2].

The Properties of Turmeric

Arthritis

Arthritis includes more than 100 different forms: the most common form is osteoarthritis, but other forms include rheumatoid arthritis, psoriatic arthritis, and related autoimmune diseases. The specific etiology of arthritis is still unknown, and there is no treatment for its underlying causes. The major goal of arthritis treatment is to reduce joint pain induced by inflammation in the joints, daily wear and tear of joints, and muscle strains. Analgesics, steroids, and nonsteroidal anti-inflammatory drugs (NSAIDs) are currently pharmaceutically to treat arthritis. These medications reduce symptoms like severe pain and inflammation. However, their long-term use cannot be sustained due to inadequate pain relief, immune disturbances, and serious gastrointestinal and cardiovascular adverse events. Therefore, herbal treatments that can reduce pain and inflammation have been investigated as potential primary or adjunct therapies for relieving arthritis symptoms ^[3].

Curcumin, demethoxycurcumin, bis-demethoxycurcumin, and turmeric essential oils constitute the majority of turmeric’s chemical composition. Turmeric is commonly used as an extract that is standardized to 80-95% curcuminoids, principally curcumin, when used as an alternative medicine or dietary supplement. Anti-inflammatory properties are seen in both turmeric and its derivatives. Turmeric modify NF-κB signaling, proinflammatory cytokines such as interleukin production and phospholipase A2, COX-2, and 5-LOX activities. Curcumin also modulates the expressions of various transcription factors involved in energy metabolism such as signal transducer and activator of transcription, peroxisome proliferator-activated receptor-c, activator protein-1, cAMP responding element binding protein, estrogen response element, and others. As a result, it has been suggested that turmeric and its constituents have positive benefits on osteoarthritis, type 2 diabetes, and dyslipidemia ^[3].

Numerous studies on people with osteoarthritis and rheumatoid arthritis have demonstrated the anti-arthritic properties of curcumin. In a randomized double-blind placebo-controlled trial for six weeks, 40 individuals with mild-to-moderate knee osteoarthritis were randomly assigned to receive either curcuminoid (500 mg/day in three divided doses; n = 19) with 5 mg piperine added to each 500-mg dosage, or a matched placebo (n = 21). When comparing the treatment group to the placebo group, there were significantly higher decreases in the visual analog scale (VAS) (p < 0.001), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores (p = 0.001), and Lequesne’s pain functional index (LPFI) (p = 0.013) scores. There were substantial improvements in the pain and physical function ratings when comparing the WOMAC subscales (p < 0.001), but not in the stiffness score. Additionally, there was less systemic oxidative stress, as measured via serum activities of superoxide dismutase (SOD) and concentrations of reduced glutathione peroxidase (GSH) and malonedialdehyde (MDA), in subjects receiving the treatment compared to the placebo. These improvements were not associated with changes in circulating cytokines. The authors suggest that the lack of changes in circulating cytokines, despite improvements in pain, may be because in osteoarthritis, inflammatory markers in the synovial fluid may be more likely elevated than systemic markers, whereas in RA, systemic markers may be more likely to be increased. Therefore, they suggest that is more plausible that the beneficial effects of curcuminoids in osteoarthritis are because of local anti-inflammatory effects rather than systemic effects ^[2].

Metabolic Syndrome

Insulin resistance, hyperglycemia, hypertension, low low high-density lipoprotein cholesterol (HDL-C), high levels of low-density lipoprotein cholesterol (LDL-C), elevated triglyceride levels, and obesity especially visceral obesity are all symptoms of the metabolic syndrome (MetS). Curcumin has been shown to attenuate several aspects of MetS by improving insulin sensitivity, suppressing adipogenesis, and reducing elevated blood pressure, inflammation, and oxidative stress. Additionally, there is evidence that curcuminoids modulate the expression of genes and the activity of enzymes involved in lipoprotein metabolism that lead to a reduction in plasma triglycerides and cholesterol and elevate HDL-C concentrations. In a randomized double-blind placebo-controlled trial with a parallel-group design, 117 MetS patients were given either 1 g of curcumin with 10 mg of piperine to improve absorption or a placebo with 10 mg of piperine for eight weeks. TNF-α, IL-6, TGF-b, and MCP-1 serum concentrations were found to be considerably lower in the curcumin group compared to the placebo group in a between-group comparison (p < 0.001). Apart from IL-6, changes in other parameters remained statistically significant after adjustment for potential confounders, including changes in serum lipids and glucose levels, as well as the baseline serum concentration of the cytokines. The findings of this study reveal that supplementing with curcumin causes people with MetS to have significantly lower serum levels of pro-inflammatory cytokines. In addition, the study looked at the cholesterol-lowering properties and found that curcuminoids were more effective than the placebo in reducing serum LDL-C, non-HDL-C, total cholesterol, triglycerides, and lipoprotein a, in addition to elevating HDL-C concentrations ^[2].

There is systematic review of 7 randomized trials of turmeric and curcumin in patients at risk of cardiovascular disease (CVD) identified evidence of their beneficial effects on serum TG and LDL-C levels, although no significant difference was found with respect to serum HDL levels. In participants with MetS, turmeric and curcumin had a positive effect on serum TC levels; however, in subjects with hyperglycemia, this positive effect on serum TC levels was not seen. It seems that the natural form (turmeric) and curcumin have more positive effects on patients suffering from MetS ^[4].

Insulin resistance (IR) is the basic underlying pathology in both Type 2 diabetes mellitus and MetS. Neerati et al. reported that curcumin could counter IR. Through amelioration of metabolic derangement and potential binding of curcumin with peroxisome proliferator-activated receptor gamma (PPAR-γ) as agonist, curcumin could play a preventive role in diet-induced insulin resistance. Moreover, curcumin was found to promote PPAR-γ, which suppressed expression of the LDL-C receptor gene, and could thereby reduce plasma LDL-C concentrations. Because it interacts with multiple targets, including peroxisome proliferator-activated receptor alpha (PPAR-α), PPAR-γ, cholesteryl ester transfer protein (CETP), and lipoprotein lipase, curcumin could probably play a role in reduction of triglyceride levels. Furthermore, curcumin is expected to affect both synthesis and catabolism of triglyceride-rich lipoproteins. As a result, curcumin supplementation may reduce the levels of triglycerides and cholesterol in the blood by reducing the expression of genes associated with lipogenesis ^[4].

 

Gastroesophageal Reflux Disease (GERD) and Gastric-ulcer

The esophagus, which carries food and liquid from the mouth to the stomach, undergoes transient lower esophageal sphincter relaxation (TLESR), which is considered the main mechanism of gastroesophageal reflux disease (GERD). Under physiological conditions, these TLESRs are induced spontaneously without swallowing and allow for the “physiological” contact of gastric juice containing hydrochloric acid (HCl) with the esophageal wall. It’s interesting to note that GERD patients experience this acid reflux more frequently during TLESR than do healthy individuals. Furthermore, the lower esophageal sphincter’s malfunction or structural anomalies in its structure can lead to more frequent or even extended exposure of the esophageal mucosa to gastric acid, which can cause reflux esophagitis and damage the esophageal mucosa. If this mucosal contact of epithelial cells with acid or acid and bile (mixed reflux) is prolonged, GERD develops. Thus, human esophageal epithelial cells are a direct target and play a key role in esophageal inflammation in response to acidic pH in the course of GERD development ^[5].

An in vitro study examining the protective potential of curcumin in esophageal epithelial cell lines exposed to exogenous acid has verified the anti-inflammatory effects of curcumin. In in vivo studies, curcumin was compared to lansoprazole, a proton pump inhibitor (PPI) that is frequently prescribed as the standard treatment for GI tract diseases such GERD. In these reports, it was demonstrated that curcumin could effectively prevent the esophageal mucosal damage induced by acute reflux esophagitis ^[5].

Anti-ulcer medications primarily target the H₂ histamine receptor (H₂R), and H₂R antagonists have been shown to inhibit gastric acid secretion in many animal model systems. Turmeric has been widely used as anti-ulcer remedy. It prevents the development of gastric by blocking H₂R. Turmeric extract has curcumin, demethoxycurcumin, bisdemethoxycurcumin, and arturmerone. Among these, the curcumin is the major component of curcuma longa and purified curcumin was more active than either demethoxy- or bisdemethoxycurcumin. Additionally, the inability of turmeric extract to inhibit β₂-adrenoceptor mediated cAMP production indicates that the active component(s) of curcuma longa extract are highly selective, inhibiting only the binding of histamine to H₂R. So this extract selectively inhibited the activation of H₂R and protected the stomach from gastric acid induced ulcers ^[6].

Side Effects

The safety and effectiveness of curcumin have been supported by numerous studies on healthy individuals. Despite this well-established safety, some negative side effects have been reported. Seven subjects who received receiving 500 – 12,000 mg in a dose response study and monitored for 72 hours reported symptoms including diarrhea, headache, rash, and yellow stool. In another study, some subjects receiving 0.45 to 3.6 g/day curcumin for one to four months reported nausea and diarrhea and an increase in serum alkaline phosphatase and lactate dehydrogenase contents ^[2].

 

References

1. Unlu A, Nayir E, Dogukan M, Kirca O, Ozdogan M. Curcumin (Turmeric) and cancer. J BUON. 2016 [cited 2022 November 21]; 21: 1050-60. Available form: https://pubmed.ncbi.nlm.nih.gov/27837604/
2. Hewlings S, Kalman D. Curcumin: A Review of Its Effects on Human Health. Foods. 2017 [cited 2022 November 21]; 6: 1-11. Available form: https://www.mdpi.com/2304-8158/6/10/92
3. Daily J, Yang M, Park S. Efficacy of Turmeric Extracts and Curcumin for Alleviating the Symptoms of Joint Arthritis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. Journal of Medicinal Food. 2016 [cited 2022 November 21]; 19: 717-29. Available form: https://www.liebertpub.com/doi/10.1089/jmf.2016.3705?url_ver=Z39.882003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
4. Qin S, Huang L, Gong J, Shen S, Huang J, Ren H, et al. Efficacy and safety of turmeric and curcumin in lowering blood lipid levels in patients with cardiovascular risk factors: a meta-analysis of randomized controlled trials. Nutrition Journal. 2017 [cited 2022 November 21]; 16: 1-10. Available form: https://nutritionj.biomedcentral.com/articles/1186/s12937-017-0293-y#Sec2
5. Kwiecien S, Magierowski M, Majka J, Ptak-Belowska A, Wojcik D, Sliwowski Z, et al. Curcumin: A Potent Protectant against Esophageal and Gastric Disorders. International Journal Molecular Sciences. 2019 [cited 2022 November 21]; 20: 1-14. Available form: https://www.mdpi.com/1422-0067/20/6/1477
6. Kim D, Kim S, Choi B, Baek N, Kim D, Kim M, et al. Curcuma longa extract protects against gastric ulcers by blocking H₂ histamine receptors. Biological and Pharmaceutical Bulletin. 2005 [cited 2022 November 21]; 28: 2220-4. Available form: https://www.jstage.jst.go.jp/article/bpb/28/12/28_12_2220/_article