Curcumin Supplementation and Human Disease: A Scoping Review of Clinical Trials

Abstract

Medicinal properties of turmeric (Curcuma longa L.), a plant used for centuries as an anti-inflammatory, are attributed to its polyphenolic curcuminoids, where curcumin predominates. Although “curcumin” supplements are a top-selling botanical with promising pre-clinical effects, questions remain regarding biological activity in humans. To address this, a scoping review was conducted to assess human clinical trials reporting oral curcumin effects on disease outcomes. Eight databases were searched using established guidelines, yielding 389 citations (from 9528 initial) that met inclusion criteria. Half focused on obesity-associated metabolic disorders (29%) or musculoskeletal disorders (17%), where inflammation is a key driver, and beneficial effects on clinical outcomes and/or biomarkers were reported for most citations (75%) in studies that were primarily double-blind, randomized, and placebo-controlled trials (77%, D-RCT). Citations for the next most studied disease categories (neurocognitive [11%] or gastrointestinal disorders [10%], or cancer [9%]), were far fewer in number and yielded mixed results depending on study quality and condition studied. Although additional research is needed, including systematic evaluation of diverse curcumin formulations and doses in larger D-RCT studies, the preponderance of current evidence for several highly studied diseases (e.g., metabolic syndrome, osteoarthritis), which are also clinically common, are suggestive of clinical benefits.

1. Introduction

Turmeric, derived from the dried rhizome of Curcuma longa L., a tropical plant native to India and southeast Asia, has been used for centuries as a spice, dye, and medicine [1]. Although multiple turmeric constituents have differential in vivo physiological effects in pre-clinical models when administered in isolation or in chemically complex turmeric extracts of variable composition [2], current interest in the medicinal turmeric properties has primarily focused on its structurally related polyphenols (curcuminoids), of which curcumin is the primary constituent (Figure 1) [3,4]. Curcuminoids comprise 3% by weight of dried turmeric rhizome and are the source of ground turmeric rhizome’s orange hue [3]. Medicinal use of turmeric has its origins in Ayurvedic medicine with a clear history of continuous use since around 500 BCE, with additional evidence suggesting its possible medicinal use since 2500 BCE, which would extend turmeric’s period of medicinal use to 4500 years [1,5].

More recently, turmeric has been adopted into Western medicinal practices. Curcuminoid-enriched turmeric supplements have been promoted in the lay press to treat various ailments from osteoarthritis to cancer. In recent decades in the United States (US), sales of minimally regulated dietary supplements are part of a large and growing global nutraceutical business [6], with botanical supplements alone bringing in USD 12.4 billion in US sales in 2021 with an annual growth rate exceeding USD 1 billion [7]. Turmeric dietary supplement use has grown in recent years as part of this trend, becoming a top-selling botanical dietary supplement in the United States [7,8]. Based on these figures and the popularity of curcumin use, it appears that people are looking for affordable, natural products to improve their lives and cure their ailments. Indeed, in recent years, use of turmeric dietary supplements, which in the US are primarily formulated to contain curcuminoid-enriched (98%) extracts [4], has been documented in epidemiologic studies by one-third of those with rheumatoid arthritis [9] and almost one-quarter of women diagnosed with breast cancer [10].

In both in vitro and/or in vivo pre-clinical studies, among other beneficial effects, curcumin has shown promise in ameliorating inflammation associated with chronic disease or infection, and limiting cancer proliferation and progression [2,11,12,13,14]. Questions remain as to whether these benefits extend to humans [15,16]. For example, despite evidence of in vivo bioactivity in rodent models, there have been concerns about curcuminoid bioavailability since curcuminoids undergo hepatic conjugation and primarily circulate as inactive glucuronides when ingested by humans (and rodents), a fate shared with many dietary polyphenols [2,17,18]. Emerging evidence, however, suggests that bioactive curcumin can be reformed in vivo from circulating curcumin glucuronides via enzymatic deconjugation [17,18]. The multiplicity of defined targets for curcuminoid action has also been a topic of concern [15], although in vivo metabolism may also provide an explanation here [2]. For example, certain oxidative curcumin metabolites have been demonstrated to form covalent adducts with specific proteins, including the proinflammatory transcription factor NFκB [19,20,21,22,23], a pharmacologic strategy also successfully employed for several FDA-approved drugs [24,25]. However, this multiplicity of action has also led curcuminoids to be labeled as “PAINS” (pan-assay interference compounds) or “IMPS” (invalid metabolic panaceas) by researchers who have additionally claimed without supporting evidence that “no double-blinded, placebo-controlled clinical trial of curcumin has been successful” [15].

To determine what level of evidence for the medicinal effects of curcuminoids (to be referred to here as curcumin) exists in human clinical trials, a scoping review of the literature was conducted. In contrast with systematic reviews, which are designed to answer narrower questions and are limited to specific study types, a scoping review methodology was chosen in order to build a comprehensive overview of the topic, identify existing evidence, and expose gaps in research [26,27]. To this end, various study designs and publication types were included in this scoping review of studies of orally administered curcumin-containing products targeted for disease treatment [26,27].

2. Results

2.1. Identification of Relevant Citations

Eight databases were systematically searched as described in the Methods section using PRISMA Extension for Scoping Reviews (PRISMA-ScR) guidelines [28], yielding 9528 citations for clinical trials testing oral administration of curcumin-containing products for disease treatment (Figure 2). After removal of 3606 duplicates, 429 animal studies, and two non-English language studies, and addition of two citations identified in references, two reviewers independently screened the remaining 5924 records. Of these citations, 4429 were excluded at the title and abstract level because of irrelevance to the topic. Titles and abstracts were rescreened, and a further 592 were excluded for irrelevance (e.g., non-oral formulations, report of clinical trial designs without data). After review of the full texts of the remaining 472 citations, the 389 citations found to meet all criteria were categorized according to disease/condition targeted with data related to trial design and findings extracted, collated, and summarized.

2.2. Types and Trends in Conditions Studied

Of the disease processes studied, curcumin clinical trials related to the treatment of metabolic abnormalities associated with obesity and insulin resistance were the most prevalent (22%) [29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110,111,112,113,114], including treatment of hyperglycemia and/or insulin resistance, hyperlipidemia, hypertension, and obesity-associated inflammation. When inclusive of citations examining non-alcoholic fatty liver disease (NAFLD) [115,116,117,118,119,120,121,122,123,124,125,126,127,128,129,130,131,132,133,134,135,136,137,138], a hepatic manifestation of metabolic syndrome [139], clinical trial citations focused on metabolic disorders (METABOLIC) accounted for almost one-third of curcumin clinical trial citations (Figure 3). Musculoskeletal (MSK) disorders were the second most common diseases targeted (17%) [140,141,142,143,144,145,146,147,148,149,150,151,152,153,154,155,156,157,158,159,160,161,162,163,164,165,166,167,168,169,170,171,172,173,174,175,176,177,178,179,180,181,182,183,184,185,186,187,188,189,190,191,192,193,194,195,196,197,198,199,200,201,202,203,204,205,206], followed by neurologic conditions (NEURO, 11%) [207,208,209,210,211,212,213,214,215,216,217,218,219,220,221,222,223,224,225,226,227,228,229,230,231,232,233,234,235,236,237,238,239,240,241,242,243,244,245,246,247,248], gastrointestinal diseases (GI, excluding NAFLD) (10%) [249,250,251,252,253,254,255,256,257,258,259,260,261,262,263,264,265,266,267,268,269,270,271,272,273,274,275,276,277,278,279,280,281,282,283,284,285,286,287], and cancer (CA, 9%) [288,289,290,291,292,293,294,295,296,297,298,299,300,301,302,303,304,305,306,307,308,309,310,311,312,313,314,315,316,317,318,319,320,321]. Together, these top five disease categories accounted for 75% of curcumin clinical trial citations. Less studied diseases or organ systems in curcumin clinical trials included the cardiovascular system (CV, 5%) [322,323,324,325,326,327,328,329,330,331,332,333,334,335,336,337,338,339,340,341], oral mucosa (4%) [342,343,344,345,346,347,348,349,350,351,352,353,354,355,356,357,358], kidney (RENAL, 3%) [359,360,361,362,363,364,365,366,367,368,369,370,371], reproductive organs (REPRO, 3%) [372,373,374,375,376,377,378,379,380,381,382], lungs (PULM, 2%) [383,384,385,386,387,388,389,390], skin (DERM, 2%) [391,392,393,394,395,396,397], or other miscellaneous disease processes (MISC, 6%) [398,399,400,401,402,403,404,405,406,407,408,409,410,411,412,413,414,415,416,417,418].

When examining trends in diseases studied over time (Figure 4), a small number (n = 15) of turmeric clinical trial citations primarily related to the treatment of gastrointestinal disorders (n = 10) appeared sporadically over a 20 year period following an initial 1986 report examining effects on post-operative inflammation [417]. However, after this period, a notable secular change occurred as curcumin clinical trial citations during the last two decades increased almost exponentially. Citations for some of the most studied disease categories reflected this dramatic rise (e.g., metabolic [with or without NAFLD] or musculoskeletal disorders), while for other disease categories, such as cancer, citation increases were more modest. Diseases that were initially a primary focus of study (e.g., gastrointestinal disorders, excluding NAFLD) were no longer the most common, while other conditions were only a focus of study within the last ten years (e.g., pulmonary, reproductive, and renal diseases), including a marked increase in citations reporting beneficial effects in NAFLD, a disease process first described 20 years ago [139].

2.3. Measures of Curcumin Clinical Trial Quality

While assessment of study quality is not an obligatory aspect of a scoping review, several key clinical trial design features were examined. Most important among these was an analysis of the prevalence of citations reporting results from double-blind, randomized placebo-controlled trials (D-RCT), a gold standard design for clinical trials [419], albeit one that tends to minimize treatment effects [420]. A D-RCT design was utilized in 70% of citations reporting curcumin clinical trial results. Amongst the top five diseases studied, a D-RCT design was most common for musculoskeletal disorders (79.1%) and least common for cancer (47.1%) (Figure 5A). Curcumin clinical trial duration was also assessed and ranged from 4 days to 30 months (Figure 5B) with an average (+/−SD) duration of 2.6 +/− 2.8 months, and median duration of 2.0 months. Trials studying neurologic disorders tended to be of longer duration (4.1 ± 4.1 months) as compared to trials for other conditions, such as metabolic disease (2.5 ± 1.9 months, p < 0.05) or musculoskeletal disorders (2.2 ± 2.0 months, p < 0.05). While the statistical power of clinical trials was not assessed in this scoping review, curcumin clinical trial study sizes were examined (Figure 5C), varying from a low of n = 4 subjects (treatment arm, n = 2) to a high of n = 624 (treatment arm, n = 313), with an average study size of n = 73 ± 68 (treatment arms, n = 35 ± 33) and a median size of n = 58 (treatment arms, n = 35). Average cohort sizes were similar across disease states, but among the most studied conditions, tended to be largest for metabolic disease (median, n = 65; range n = 4–358), followed by musculoskeletal disorders (median, n = 49; range n = 10–552).

Almost all curcumin trials assessed treatment effects of curcumin products formulated to contain turmeric-derived curcuminoid-enriched extracts that are broadly analogous to most turmeric supplements sold in the United States [4]. Due to concerns about curcumin bioavailability, a large share (55%) of the US turmeric dietary supplement market is comprised of products formulated to enhance curcumin bioavailability, including proprietary products where curcuminoid extracts are often combined with some type of lipophilic carrier to increase absorption, or products combining curcumin with piperine to decrease metabolism [4]. The proportion of curcumin clinical trials testing enhanced bioavailability curcumin products was therefore also evaluated (Figure 5D). Overall, 45% of curcumin clinical trials assessed enhanced bioavailability curcumin products. Among the most commonly studied diseases, enhanced bioavailability curcumin products were most studied for musculoskeletal disorders (61.2%), while gastrointestinal disorders (GI) were among the lowest (20.5%), likely due to intestinal (not systemic) targeting in most (69%) GI studies. The prevalent use of curcumin products with improved bioavailability impedes meaningful comparison of curcuminoid doses tested across studies. This is due to the variable effects of these products on curcumin bioavailability, which are rarely evaluated within the context of clinical trials. Because a meaningful comparison of curcuminoid dosing across citations was therefore not possible, dosing information was not analyzed.

2.4. Side Effects Reported in Curcumin Clinical Trial Citations

The most frequently reported side effects associated with curcumin included GI symptoms (diarrhea, abdominal pain, flatulence, yellow stools, dyspepsia, nausea, vomiting, GI distress, constipation), headache, and dizziness. Most were classified as mild. Serious side effects were uncommon but included a single report of worsening cachexia and muscle wasting in a pancreatic cancer trial, resulting in increased morbidity and mortality [313], as well as an increased incidence of acute kidney injury with perioperative curcumin treatment when undergoing elective abdominal aortic aneurysm repair [336]. Uncommon side effects included hair loss, mild fever, and throat infection.

2.5. Clinical Trials for Metabolic Disorders

Clinical trial citations reporting curcumin-associated effects on disordered glucose and lipid metabolism, including those focused on NALFD, represented almost one-third of curcumin clinical trial citations [29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110,111,112,113,114,115,116,117,118,119,120,121,122,123,124,125,126,127,128,129,130,131,132,133,134,135,136,137,138]. Most of these studies utilized a D-RCT design (76%), and 48% focused on enhanced bioavailability curcumin products. The studies evaluating metabolic disorders included relatively large cohorts (mean, n = 88), and had an average study duration of 2.5 months. In study populations described as healthy or hyperlipidemic [29,30,31,32,33,34,35,36,37,38,39,40,41,42,43], representing only 14% of citations in this category (Figure 6A), beneficial effects of curcumin on lipid or glucose metabolism were uncommon. In contrast, the majority of citations for studies evaluating the metabolic effects of curcumin in insulin-resistant populations with obesity (26% of studies in this category) [44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68], metabolic syndrome (15%) [69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85], or type 2 diabetes mellitus (26%) [86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110,111,112,113,114] reported positive outcomes for commonly studied endpoints. These endpoints included lipids (72%), glucose and/or HbA_1c levels (82%), measures of insulin resistance (92%), biomarkers of inflammation (61%) or oxidative stress (69%), and/or improvements in weight/BMI (73%). The majority of citations for clinical trials in populations with NAFLD (a hepatic manifestation of metabolic syndrome) populations (23% of studies in this category) [115,116,117,118,119,120,121,122,123,124,125,126,127,128,129,130,131,132,133,134,135,136,137,138], also reported beneficial outcomes for glucose (83%) and lipid (75%) metabolism. Improved liver function (n = 11 of 16 studies where this was examined) and/or liver steatosis or fibrosis (n = 5 of 6 studies) were also reported.

2.6. Clinical Trials for Musculoskeletal Disorders

Disorders of the musculoskeletal system were the second most studied category (17% of total) [140,141,142,143,144,145,146,147,148,149,150,151,152,153,154,155,156,157,158,159,160,161,162,163,164,165,166,167,168,169,170,171,172,173,174,175,176,177,178,179,180,181,182,183,184,185,186,187,188,189,190,191,192,193,194,195,196,197,198,199,200,201,202,203,204,205,206]. Most of these citations reported D-RCT results (79%) of enhanced bioavailability products (61%) and had an average study duration of 2.2 months. The most common MSK disorder studied was osteoarthritis (46%) (Figure 6B) [140,141,142,143,144,145,146,147,148,149,150,151,152,153,154,155,156,157,158,159,160,161,162,163,164,165,166,167,168,169,170], a common age-related joint disorder for which obesity, as with metabolic dysfunction, is a risk factor. Muscle outcomes related to sports performance or exercise (e.g., soreness) comprised the second most common musculoskeletal condition studied (36%) [171,172,173,174,175,176,177,178,179,180,181,182,183,184,185,186,187,188,189,190,191,192,193,194]. The remaining 18% of MSK citations reported trial results for miscellaneous disorders, including autoimmune rheumatic disorders (rheumatoid arthritis [n = 5 citations] [195,196,197,198,199], systemic lupus erythematosus [SLE, n = 3] [200,201,202], ankylosing spondylitis [AS, n = 1] [203]) or osteoporosis (n = 3) [204,205,206], including menopause-related bone loss where bone protective effects were reported [205]. Most osteoarthritis trials reported clinical outcomes [140,141,142,143,144,145,146,147,148,149,150,151,152,153,154,155,156,157,158,159,160,161,162,163,164,165,166,167,168,169,170], with approximately half also reporting treatment effects on various biomarkers. Most clinical outcomes, including pain (92%) and function (86%), as well as biomarkers of inflammation, oxidative stress, and cartilage degradation (80%), showed positive effects or equivalency to non-steroidal anti-inflammatory drugs (NSAIDs). The results also indicated a reduced need for rescue medications. In trials examining curcumin effects on exercise-related changes in muscle [171,172,173,174,175,176,177,178,179,180,181,182,183,184,185,186,187,188,189,190,191,192,193,194], the second most studied MSK condition (n = 24), at least half of the citations provided data for each of several different clinical and/or biomarker outcomes. Most studies reported beneficial effects on pain (82%) or functional outcomes (75%), as well as reductions in creatinine kinase levels (58%), a measure of muscle damage, and/or beneficial effects on other biomarkers (e.g., inflammation or oxidative stress) (56%). The third most studied musculoskeletal condition (7%, n = 5 citations), rheumatoid arthritis, is an autoimmune disorder distinct from osteoarthritis. Here, results were mixed [195,196,197,198,199], with only two D-RCTs out of four RA studies (of which n = 3 were D-RCTs) demonstrating improved clinical outcomes as well as significant improvements in biomarkers of inflammation [195,197].

2.7. Clinical Trials for Neuropsychiatric Disorders

Neuropsychiatric disorders comprised the third most commonly studied category of disorders (11% of citations, n = 42) (Figure 6C) [207,208,209,210,211,212,213,214,215,216,217,221,222,223,224,225,226,227,228,229,230,231,232,233,234,235,236,237,238,239,240,241,242,243,244,245,246,247,248], with most citations reporting results from D-RCT studies (71%). Studies were of longer duration (4.1 months) compared to most other top categories (p < 0.05), with half testing enhanced bioavailability products (50%). While a range of conditions was studied (e.g., migraine [n = 6 citations reporting unique data from two studies] [207,208,209,210,211,212], schizophrenia [n = 4] [213,214,215,216], amyotrophic lateral sclerosis [ALS, n = 4] [217,218,219,220], multiple sclerosis [MS, n = 3] [221,222,223], neurofibromatosis [n = 1] [224], or traumatic brain injury n = 1] [225]), more than half of the citations focused either on depression (n = 13, 31%) [226,227,228,229,230,231,232,233,234,235,236,237,238] or cognition (n = 10, 24%) [239,240,241,242,243,244,245,246,247,248]. Clinical trial citations reporting curcumin effects on depression in populations with or without a major depressive disorder were numerous [226,227,228,229,230,231,232,233,234,235,236,237,238] but with mixed results; an absence of effect was noted in half of the reports, while in other citations differences were reported with respect to ameliorating depression vs. anxiety. For clinical trials related to cognition, two D-RCTs conducted over a decade ago reported negative results in probable Alzheimer’s disease populations when examining non-bioenhanced curcumin in 6-month-long studies [247,248]. These were followed in the last decade by seven D-RCT that were larger (n = 20–50 per arm vs. n = 10 in AD) and tested enhanced bioavailability products in a different population, aged adults without dementia or AD [239,240,241,242,243,244,246]. Benefits were reported in all but one [244] of these later cognition studies, which also used more detailed assessments of cognition. Additionally, two studies examining positron emission tomography (PET) imaging of brain plaques also reported improvements [243,246].

2.8. Clinical Trials for Gastrointestinal Disorders (Excluding Cancer)

Clinical trials examining curcumin effects on gastrointestinal (GI) disorders [249,250,251,252,253,254,255,256,257,258,259,260,261,262,263,264,265,266,267,268,269,270,271,272,273,274,275,276,277,278,279,280,281,282,283,284,285,286,287], a primary focus of early curcumin trials more than twenty years ago, represented only 10% of citations when excluding NAFLD (Figure 6D). The percentage of GI citations reporting D-RCT results (59%) was lower than in previously discussed categories. Testing of enhanced bioavailability products was also less common (21%). Most studies focused on the intestines (69%, n = 27), including disorders of the foregut (n = 13) [249,250,251,252,253,254,255,256,257,258,259,260,261], small intestine (n = 4) [262,263,264,265], and colon (n = 10) [266,267,268,269,270,271,272,273,274,275]; additional citations focused on gallbladder (n = 6) [276,277,278,279,280,281] and liver (n = 6) [282,283,284,285,286,287]. When considered by disease pathogenesis, foregut conditions related to disordered gastric secretion, including peptic ulcer disease and Barrett’s esophagitis, were the most frequently studied (33%, n = 13) [249,250,251,252,253,254,255,256,257,258,259,260,261], followed by inflammatory bowel disease (IBD; 26%, n = 10), including Crohn’s disease or ulcerative colitis [262,263,268,269,270,271,272,273,274,275]. Studies evaluating curcumin effects on peptic ulcer disease or Barrett’s esophagitis were among some of the earliest trials and have continued to the present; however, these trials have yielded mixed results with little evidence of improved symptoms and mixed reports on healing and/or reduction of H. pylori infections [249,250,251,252,253,254,255,256,257,258,259,260,261]. While less numerous, results from clinical trials evaluating curcumin effects on IBD were more consistent. Almost two decades ago, the first trials related to IBD appeared; a D-RCT ulcerative colitis (UC) trial reported a beneficial effect of curcumin [270] while no effect was seen in a D-RCT study of a mixed population with UC or Crohn’s disease [268]. With the exception of one study [271], subsequent UC trials over the last decade (n = 6) have consistently reported reductions in clinical symptoms as well as endoscopic improvement and/or decreases in calprotectin or other disease activity biomarkers [268,269,270,271,272,273,274,275]. Curcumin effects on IBD affecting the small bowel (Crohn’s disease) were less clear with benefits reported in only one of two recent D-RCT trials [262,263]. Citations reporting curcumin effects on disorders of the oral mucosa (n = 17) were grouped separately from gastrointestinal disorders (oral mucosa, Figure 3) and primarily focused on gingivitis, canker sores, oral lichen planus, or submucosal fibrosis, reporting benefits on variable endpoints. However, only 35% of these oral mucosa studies were D-RCT [342,343,344,345,346,347,348,349,350,351,352,353,354,355,356,357,358].

2.9. Clinical Trials for Cancer

Cancer clinical trial citations were the fifth largest category [288,289,290,291,292,293,294,295,296,297,298,299,300,301,302,303,304,305,306,307,308,309,310,311,312,313,314,315,316,317,318,319,320,321], comprising 9% of total citations (n = 34) (Figure 6E). Although most cancer studies were conducted during recent decades, a minority were D-RCTs (47%) and only half evaluated the effects of enhanced bioavailability products. These studies were of average size (mean, n = 60) and duration (mean = 2.6 months) relative to the other major categories. The number of studies focused on cancer was relatively small, especially when considering the range of diverse cancers studied, including prostate (n = 5) [288,289,290,291,292], breast (n = 5) [293,294,295,296,297], colorectal or its precursors (n = 4) [298,299,300,301], multiple myeloma (n = 4) [302,303,304,305], head and neck (n = 3) [306,307,308], gynecologic (n = 3) [309,310,311], pancreatic (n = 2) [312,313], gastric (n = 1) [314], thyroid (n = 1) [315], and bladder (n = 1) [316], as well as studies evaluating solid tumors of various types (n = 5) [317,318,319,320,321]. Endpoints varied with cancer type and focused on the amelioration of treatment-related side effects, rather than disease progression. For instance, among four D-RCTs examining the effects of curcumin on prostate cancer, one study reported reductions in biomarkers of oxidative stress [290], two studies reported benefits for urinary symptoms, including those secondary to benign prostatic hypertrophy [289,291], and one study did not find any effects on radiation-induced toxicity [292]. The five breast cancer citations reported on disparate endpoints, including the effects of radiation-induced dermatitis (n = 3 [n = 2 D-RCT]) [295,296,297], with the results indicating a lack of improvement in inflammatory biomarkers, pain, or quality of life, and mixed outcomes with respect to dermatitis. The two remaining non-D-RCT breast cancer citations reported an improved response rate to anthracycline-based neoadjuvant chemotherapy (non-D-RCT) and improved quality of life and hematologic parameters during paclitaxane therapy (case series) [293,294]. Colorectal cancer (CRC) citations (n = 4) in diverse populations focused on prevention (no effect), response to chemotherapy or radiation (no effect), or tolerability in metastatic CRC. Solid tumor citations evaluating amelioration of chemotherapy and/or radiation-induced side effects (n = 4) reported positive effects [317,318,320]; body composition was unchanged in a fifth solid tumor study [321]. This latter finding stands in stark contrast to a severe adverse effect of curcumin on body composition documented in a pancreatic cancer trial [313].

2.10. Clinical Trials for Less Commonly Studied Disorders

Among the less commonly studied disorders (Other, Figure 4), cardiovascular trial citations (5% of total citations, n = 20) [322,323,324,325,326,327,328,329,330,331,332,333,334,335,336,337,338,339,340,341] primarily focused on the vasculature (n = 11, e.g., compliance and endothelial function) [322,323,324,325,326,327,328,329,330,331,332]. These studies generally reported improvements in subjects who were healthy or had a range of dysfunction, excluding children (here with tetralogy of Fallot [332]), who, it should be noted, were rarely included in curcumin clinical trials. Renal clinical trial citations (3%, n = 13) [359,360,361,362,363,364,365,366,367,368,369,370,371], which examined a range of endpoints and conditions, including contrast-induced nephropathy, diabetic nephropathy, and end-stage renal disease, were too disparate and few in number to discern specific patterns of response. Reproductive organ trial citations (3%, n = 11) [372,373,374,375,376,377,378,379,380,381,382] examined a range of disorders, with polycystic ovarian syndrome (PCOS), a condition associated with insulin resistance [421], being the most common (n = 4) [372,373,374,375,376,377,378,379,380,381,382] where improvements in metabolic function were noted analogous to outcomes reported in other insulin-resistant populations. Pulmonary clinical trial citations (2%, n = 8) [383,384,385,386,387,388,389,390] mostly focused on asthma (n = 5) [384,385,386,387,388], where benefits were reported in all trials, including one focused on children [388]. Dermatological trial citations (2%, n = 7) that focused on inflammatory skin conditions due to autoimmune disorders or external irritants reported benefits (n = 4) [391,392,393,394], while no effects on erythema or barrier function were noted with normal skin (n = 3) [395,396,397]. Miscellaneous other diseases (6%, n = 21) with even fewer citations (e.g., infectious diseases [n = 4] [398,399,400,401], ophthalmologic [n = 4] [402,403,404,405], or hematological disorders [n = 4] [406,407,408,409]) were grouped together, and due to their variability and small numbers cannot be easily summarized [398,399,400,401,402,403,404,405,406,407,408,409,410,411,412,413,414,415,416,417,418]. However, inflammatory or oxidative stress biomarkers were frequent endpoints for these studies, which yielded generally consistent reports of improvement (e.g., decreased inflammatory cytokines in COVID-19 patients [401]).

3. Discussion

Humans have used curcumin-containing turmeric (Curcuma longa L.) medicinally for thousands of years, primarily for the treatment of inflammatory conditions, as documented by historical medical texts and archeological evidence. While continuous medicinal use for such an extended time period is supportive of the likelihood that curcumin can yield biological effects in humans, this scoping review of curcumin clinical trial outcomes was undertaken to assess scientific evidence querying this postulate, both with respect to diseases treated and biological processes targeted. After a comprehensive search of eight databases for publications, abstracts, and clinicaltrials.gov citations from 1900 to 2020, strong scientific evidence emerged from clinical trials, which primarily (70%) utilized gold standard D-RCT designs, indicating that curcumin can impact disease conditions in humans. Evidence was strongest for highly studied diseases where inflammation, which remains an important etiologic contributor for over 50% of deaths worldwide [422], is an important disease driver. Scientific evidence of anti-inflammatory effects of curcumin in humans demonstrated through clinical and biomarker endpoints in clinical trials for various diseases adds to a long history of evidence stretching back millennia from ethnobotanical use and is consistent with modern molecular evidence of curcumin blockade of key mediators of inflammation [19,20,22,23].

Systematic comparison of botanical studies for scoping or systematic reviews is difficult due to the disparate chemical composition of plant-derived products tested, which is also often not well validated. Additionally, the testing of various enhanced bioavailability curcumin products (45% of all citations), while particularly relevant due to their commercial availability to consumers (55% of turmeric supplements sold in the United States [4]), also makes study comparisons difficult. While direct comparisons by curcumin dose across studies is thus an invalid means of comparison, by limiting our analysis to studies testing the oral administration of curcumin-containing products for disease treatment, where curcumin was the only variable tested, distinct patterns still emerged. This was most notable for the two most frequently studied disorders. For each of several clinical and biomarker endpoints tested, beneficial curcumin effects were noted on average in 79% of trials investigating: (1) metabolic disorders caused by obesity-associated inflammation and insulin resistance [423], which represented 29% of the citations (n = 114) when including polycystic ovary syndrome (PCOS); or (2) osteoarthritis which represented 8% of the citations (n = 31), and is also an inflammatory disorder with obesity as a major risk factor [424]. Despite a minority of citations in these two categories not reporting benefits for certain endpoints, which may be due to factors such as differences in study population, power, endpoints studied, product choice, dosing, or duration, the majority of evidence for these widely studied disease processes (predominantly derived from gold-standard D-RCTs [76–79%] that also included some of the largest studies, thus minimizing bias [425]), supported the health benefits of curcumin for these populations. Thus, consistent with the high prevalence of obesity in the United States (42% of US adults [426]), these findings suggest the possibility that large segments of the US adult population may potentially derive benefits from curcumin use, including adults with: (1) pre-diabetes (38% of US adults [427]) where lifestyle management is key; (2) diabetes (11% [428]); and/or 3) osteoarthritis (11% [429]).

There are of course caveats and limitations associated with any conclusions drawn from scoping reviews assessing the general state of a field, as compared to a systematic review or meta-analysis. However, clear benefits also accrue, as was perhaps most notable here for cancer clinical trial citations. Unlike citations related to metabolic syndrome or musculoskeletal inflammation that comprised half of the available literature and were primarily D-RCTs testing enhanced bioavailability products in larger cohorts, cancer trial citations did not provide a strong evidence base for curcumin use due to low citation numbers and trial designs. Evidence for symptom management was sparse given the small number of citations available for any given tumor type and effects on disease progression were rarely a focus of study. Cancer trial quality, in general, was lower than for other topics (e.g., only 47% D-RCT) with trends over time suggesting that this topic is not a strong focus of current interest. This contrasts with current usage patterns, however, as, for example, 16% of breast cancer survivors in a recent large epidemiologic study reported concurrent curcumin use during chemotherapy despite an absence of data supporting efficacy, or, perhaps even more importantly, safety when used in this context [10]. The serious adverse effects of curcumin reported in one pancreatic cancer trial stand as a cautionary tale when considering use in a cancer population [313].

Secular trends uncovered by this scoping review also yielded interesting findings suggestive of a maturation in certain fields of study. This was most notable for curcumin clinical trials evaluating cognition and memory, where two early negative D-RCTs evaluating non-bioenhanced curcumin in Alzheimer’s disease (AD) populations [247,248] were followed by multiple D-RCT trials with generally positive outcomes focusing on prevention in aging non-AD populations in studies that were higher powered and tested enhanced bioavailability products [239,240,242,243,244,245,246]. A careful review of the entirety of curcumin clinical trial citations also yielded insights that could be missed in more focused disease-specific queries. For example, in curcumin trials focused on diseases affecting the gastrointestinal (GI) mucosa, evidence of benefits was most robust for colonic disorders and weaker for upper GI tract disorders, which may be due to the differential disposition and metabolism of curcumin in the gastrointestinal system, where curcumin is eliminated via the enterohepatic circulation and the microbiome likely impacts its metabolism [2,430]. Another strength of this scoping review was our inclusion of abstracts and other forms of unpublished data, a strategy that can help to mitigate publication bias, which can adversely affect outcomes for both scoping and systematic reviews [26,27].

One limitation of this scoping review is the lack of inclusion of 2021–2022 citations due to pandemic-related delays in data analysis after identification of citations. However, this circumstance allows for comparison of results from this scoping review with those of a systematic review of curcumin clinical trials completed in 2020 [431], which provides both corroborating and additional evidence [431]. The two studies cannot be directly compared since citations in the systematic review were not identified and were fewer in number despite additional inclusion of trials with non-oral curcumin delivery and botanical mixtures, albeit after searching only four databases (vs. eight here) with an earlier end date (mid-2020 vs. end of 2020 here). However, certain comparisons are instructive. Risk of bias assessments in the systematic review exceeded our quality assessment of curcumin clinical trials based on D-RCT design (70% of citations in this scoping review) by inclusion of two additional criteria, incomplete outcome data acknowledgment and selective reporting. The systematic review reported a 48% compliance rate for all parameters in curcumin trials assessed, which increased to 67% in recent years, an encouraging trend consistent with general findings reported here, where many—but not all—studies utilized optimal designs. Additionally, and in contrast with the types of information summarized in the cancer-focused systematic review [431], a particular strength of this scoping review is its summation of curcumin clinical trial outcomes for all diseases using mechanistic groupings (e.g., metabolic disorders associated with obesity), which provides a unique perspective and contribution to the curcumin literature, including citations and search strategies.

Lastly, it is important to note that few clinical trials analyzed in this scoping review examined dose-dependent effects of a single agent, comparative effects of disparate products, and/or provided pharmacokinetic data to facilitate cross-comparison across studies. Thus, best practices for clinical curcumin use, even in conditions where the preponderance of existing evidence supported benefits, remain uncertain and would benefit from the conduct of additional well-funded and carefully designed studies, informed by over three decades of curcumin clinical trial results, as summarized here.

In conclusion, based on the results of this scoping review, curcumin does appear to have biological activity in humans, with significant evidence that curcumin may have medicinal benefits in the treatment of certain inflammatory and/or obesity-related conditions that are common contributors to higher mortality, morbidity, and loss of productivity in the workforce.

4. Methods

4.1. Design of Systematic Literature Search

A literature review was conducted using recommended five-step scoping review guidelines [26,27]: (1) identify a research question (outcomes and diseases targeted in clinical trials assessing curcuminoid-containing turmeric products); (2) identify relevant studies; (3) select relevant studies; (4) chart data from these studies; and (5) collate, summarize, and report the results. Following reporting guidelines specified in the “PRISMA Extension for Scoping Reviews (PRISMA-ScR,)” [28], a medical librarian (CLH) used both controlled vocabulary terms (e.g., MeSH, Emtree) and keywords to search the following eight databases for clinical studies of curcuminoids in the treatment of medical conditions in humans using database-specific search strategies (Supplemental Figure S1): Ovid/MEDLINE (1966–2020), Cochrane Central (1996–2020), Elsevier/Embase (1947–2020), Clarivate/WOS (1900–2020), EBSCO/CINAHL (1937–2020), EBSCO/PsycInfo (1887–2020), AMED (1985–2020), and ClinicalTrials.gov (1997–2020). Initial searches were completed on 28 May 2019, and updated on 20–21 December 2020. An English language filter was applied; there were no publication date or publication type limits. Additional citations listed within studies were also screened.

4.2. Methods for Assessing Citation Inclusion

All identified records were exported to the management software EndNote Version X9 (Clarivate Analytics, Philadelphia, PA, USA), which was used to document and delete duplicate records and pre-screen out animal studies and publications unavailable in English (CLH). Two independent reviewers (TMP, BB) screened the titles and abstracts of all remaining articles for relevance to the topic. Disagreements were resolved by consensus and consultation with the senior author (JLF). The remaining titles and abstracts were then rescreened for relevance, only retaining citations for clinical trials testing oral formulations with study designs allowing for assessment of curcuminoid products as a sole variable (curcuminoid products containing piperine to enhance curcumin bioavailability were retained). Citations reporting different outcomes from a single study were retained, while citations lacking trial data (e.g., study design only) or referencing duplicate data from a single study were excluded.

4.3. Data Extraction and Synthesis

All included citations were categorized according to general organ system and further subdivided into disease categories (JFL). All citations for a given organ system were read in their entirety by a single reviewer (TMP, BB, MH, AMR). The following data were extracted and collated from the selected publications: year of publication, disease and population studied, study design, study size and duration, product type and dose, and disease outcomes assessed (clinical and lab-based). Collated data for a given organ system and/or disease were then summarized for report here (TPM, a 4th year medical student; and JLF, an internist and clinical endocrinologist). Limited statistical analyses, consistent with the design and purpose of this scoping review, were conducted using Prism software (GraphPad, San Diego, CA, USA).

Author Contributions

Conceptualization, J.L.F. and C.L.H.; Methodology, C.L.H.; Validation, C.L.H. and J.L.F.; Formal Analysis, C.L.H., T.M.P., B.B., M.H., A.M.R. and J.L.F.; Investigation C.L.H., T.M.P. and B.B.; Resources, J.L.F. and C.L.H.; Data curation, C.L.H., T.M.P. and B.B.; Writing—original draft preparation, T.M.P., J.L.F. and C.L.H.; Writing-review and editing, J.L.F., C.L.H., T.M.P., B.B., M.H. and A.M.R.; Visualization, T.M.P., J.L.F. and C.L.H.; Supervision, J.L.F.; Project Administration, J.L.F.; Funding, T.M.P. and M.H. All authors have read and agreed to the published version of the manuscript.

Data Availability Statement

No new data were created in this study; all citations are publicly available.

Conflicts of Interest

The authors declare no conflict of interest.

Footnotes

Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Figures

Figure 1. Chemical structures of turmeric-derived curcuminoids, of which curcumin is the most abundant.

Figure 2. Preferred Reporting Items for Systematic Reviews (PRISMA) flow diagram of scoping review process used to search literature and extract citations meeting inclusion criteria.

Figure 3. Turmeric clinical trials by organ system or disease process. Clinical trials were organized for analysis by organ system (e.g., musculoskeletal [MSK], neuropsychiatric [NEURO], gastrointestinal [GI], cardiovascular [CV], oral mucosa, renal, reproductive organs [REPRO], pulmonary [PULM], or dermatologic [DERM] disorders) or disease process (metabolic disorders including non-alcoholic fatty liver disease [METABOLIC + NAFLD] or cancer [CA]).

Figure 4. Publication timeline for curcumin clinical trials. Citations per year are presented in stacked plots to demonstrate secular trends for the five most common categories, including metabolic (with NAFLD graphed separately), musculoskeletal (MSK), neuropsychiatric (NEURO), and gastrointestinal (GI, excluding NAFLD) disorders or cancer [CA]. All other diseases (OTHER) are graphed as a group.

Figure 5. Curcumin clinical trial design elements by disease category. (A) Prevalence of citations reporting double-blind, randomized, placebo-controlled (D-RCT) trial results. (B) Curcumin clinical trial duration or (C) size, noting individual citations (open circles) and averages (red line). (D) Prevalence of citations reporting enhanced bioavailability curcuminoid product treatment effects.

Figure 6. Frequency of specific conditions studied within each of the top five categories, which together accounted for 75% of curcumin clinical trial citations. N = number of citations.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/ijms24054476/s1.

References

1. Velayudhan, K.C.; Dikshit, N.; Nizar, M.A. Ethnobotany of turmeric (Curcuma longa L.). Indian J. Tradit. Knowl.; 2012; 11, pp. 607-614.

2. Funk, J.L.; Schneider, C. Perspective on Improving the Relevance, Rigor, and Reproducibility of Botanical Clinical Trials: Lessons Learned From Turmeric Trials. Front. Nutr.; 2021; 8, 782912. [DOI: https://dx.doi.org/10.3389/fnut.2021.782912] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/34926556]

3. Pawar, H.A.; Karde, M.; Mundle, N.; Jadhav, P.R.; Mehra, K. Phytochemical Evaluation and Curcumin Content Determination of Turmeric Rhizomes Collected From Bhandara District of Maharashtra (India). Med. Chem.; 2014; 4, pp. 588-591. [DOI: https://dx.doi.org/10.4172/2161-0444.1000198]

4. Skiba, M.B.; Luis, P.B.; Alfafara, C.; Billheimer, D.; Schneider, C.; Funk, J.L. Curcuminoid Content and Safety-Related Markers of Quality of Turmeric Dietary Supplements Sold in an Urban Retail Marketplace in the United States. Mol. Nutr. Food Res.; 2018; 62, 1800143. [DOI: https://dx.doi.org/10.1002/mnfr.201800143] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/29808963]

5. Bates, J. Oilseeds, spices, fruits and flavour in the Indus Civilisation. J. Archaeol. Sci. Rep.; 2019; 24, pp. 879-887. [DOI: https://dx.doi.org/10.1016/j.jasrep.2019.02.033]

6. Blaze, J. A Comparison of Current Regulatory Frameworks for Nutraceuticals in Australia, Canada, Japan, and the United States. Innov. Pharm.; 2021; 12, [DOI: https://dx.doi.org/10.24926/iip.v12i2.3694]

7. Smith, T.; Resetar, H.; Morton, C. US Sales of Herbal Supplements Increase by 9.7% in 2021. HerbalEgram; 2022; Available online: https://www.herbalgram.org/resources/herbalegram/volumes/volume-19/issue-11-november/news-and-features-1/2021-herb-market-report/ (accessed on 20 February 2023).

8. Linstrom, A.; Ooyen, C.; Lynch, M.E.; Blumenthal, M. Herb Supplement Sales Increase 5.5% in 2012: Herbal Supplement Sales Rise for the 9th Consecutive Year; Turmeric Sales Jump 40% in Natural Channel. HerbalGram; 2013; 99, pp. 60-65.

9. Skiba, M.B.; Hopkins, L.L.; Hopkins, A.L.; Billheimer, D.; Funk, J.L. Nonvitamin, Nonmineral Dietary Supplement Use in Individuals with Rheumatoid Arthritis. J. Nutr.; 2020; 150, pp. 2451-2459. [DOI: https://dx.doi.org/10.1093/jn/nxaa197]

10. Hauer, M.; Rossi, A.; Wertheim, B.; Kleppel, H.; Bea, J.; Funk, J.L. Dietary Supplement Use in Women Diagnosed with Breast Cancer. J. Nutr.; 2023; [DOI: https://dx.doi.org/10.1016/j.tjnut.2022.12.007]

11. Epstein, J.; Sanderson, I.R.; Macdonald, T.T. Curcumin as a therapeutic agent: The evidence from in vitro, animal and human studies. Br. J. Nutr.; 2010; 103, pp. 1545-1557. [DOI: https://dx.doi.org/10.1017/S0007114509993667]

12. Giordano, A.; Tommonaro, G. Curcumin and Cancer. Nutrients; 2019; 11, 2376. [DOI: https://dx.doi.org/10.3390/nu11102376] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31590362]

13. Singh, L.; Sharma, S.; Xu, S.; Tewari, D.; Fang, J. Curcumin as a Natural Remedy for Atherosclerosis: A Pharmacological Review. Molecules; 2021; 26, 4036. [DOI: https://dx.doi.org/10.3390/molecules26134036] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/34279384]

14. Šudomová, M.; Hassan, S.T.S. Nutraceutical Curcumin with Promising Protection against Herpesvirus Infections and Their Associated Inflammation: Mechanisms and Pathways. Microorganisms; 2021; 9, 292. [DOI: https://dx.doi.org/10.3390/microorganisms9020292] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/33572685]

15. Nelson, K.M.; Dahlin, J.L.; Bisson, J.; Graham, J.; Pauli, G.F.; Walters, M.A. The Essential Medicinal Chemistry of Curcumin. J. Med. Chem.; 2017; 60, pp. 1620-1637. [DOI: https://dx.doi.org/10.1021/acs.jmedchem.6b00975] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/28074653]

16. Nelson, K.M.; Dahlin, J.L.; Bisson, J.; Graham, J.; Pauli, G.F.; Walters, M.A. Curcumin May (Not) Defy Science. ACS Med. Chem. Lett.; 2017; 8, pp. 467-470. [DOI: https://dx.doi.org/10.1021/acsmedchemlett.7b00139]

17. Kunihiro, A.G.; Luis, P.B.; Frye, J.B.; Chew, W.; Chow, H.H.; Schneider, C.; Funk, J.L. Bone-Specific Metabolism of Dietary Polyphenols in Resorptive Bone Diseases. Mol. Nutr. Food Res.; 2020; 64, e2000072. [DOI: https://dx.doi.org/10.1002/mnfr.202000072]

18. Kunihiro, A.G.; Luis, P.B.; Brickey, J.A.; Frye, J.B.; Chow, H.S.; Schneider, C.; Funk, J.L. Beta-Glucuronidase Catalyzes Deconjugation and Activation of Curcumin-Glucuronide in Bone. J. Nat. Prod.; 2019; 82, pp. 500-509. [DOI: https://dx.doi.org/10.1021/acs.jnatprod.8b00873]

19. Schneider, C.; Gordon, O.N.; Edwards, R.L.; Luis, P.B. Degradation of Curcumin: From Mechanism to Biological Implications. J. Agric. Food Chem.; 2015; 63, pp. 7606-7614. [DOI: https://dx.doi.org/10.1021/acs.jafc.5b00244] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/25817068]

20. Joseph, A.I.; Edwards, R.L.; Luis, P.B.; Presley, S.H.; Porter, N.A.; Schneider, C. Stability and anti-inflammatory activity of the reduction-resistant curcumin analog, 2,6-dimethyl-curcumin. Org. Biomol. Chem.; 2018; 16, pp. 3273-3281. [DOI: https://dx.doi.org/10.1039/C8OB00639C]

21. Gordon, O.N.; Luis, P.B.; Sintim, H.O.; Schneider, C. Unraveling curcumin degradation: Autoxidation proceeds through spiroepoxide and vinylether intermediates en route to the main bicyclopentadione. J. Biol. Chem.; 2015; 290, pp. 4817-4828. [DOI: https://dx.doi.org/10.1074/jbc.M114.618785]

22. Edwards, R.L.; Luis, P.B.; Varuzza, P.V.; Joseph, A.I.; Presley, S.H.; Chaturvedi, R.; Schneider, C. The anti-inflammatory activity of curcumin is mediated by its oxidative metabolites. J. Biol. Chem.; 2017; 292, pp. 21243-21252. [DOI: https://dx.doi.org/10.1074/jbc.RA117.000123] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/29097552]

23. Edwards, R.L.; Luis, P.B.; Nakashima, F.; Kunihiro, A.G.; Presley, S.H.; Funk, J.L.; Schneider, C. Mechanistic Differences in the Inhibition of NF-κB by Turmeric and Its Curcuminoid Constituents. J. Agric. Food Chem.; 2020; 68, pp. 6154-6160. [DOI: https://dx.doi.org/10.1021/acs.jafc.0c02607] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/32378408]

24. Roskoski, R., Jr. Orally effective FDA-approved protein kinase targeted covalent inhibitors (TCIs). Pharmacol. Res.; 2021; 165, 105422. [DOI: https://dx.doi.org/10.1016/j.phrs.2021.105422] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/33434619]

25. Lagoutte, R.; Patouret, R.; Winssinger, N. Covalent inhibitors: An opportunity for rational target selectivity. Curr. Opin. Chem. Biol.; 2017; 39, pp. 54-63. [DOI: https://dx.doi.org/10.1016/j.cbpa.2017.05.008]

26. Levac, D.; Colquhoun, H.; O’Brien, K.K. Scoping studies: Advancing the methodology. Implement. Sci.; 2010; 5, 69. [DOI: https://dx.doi.org/10.1186/1748-5908-5-69]

27. Arksey, H.; O’Malley, L. Scoping studies: Towards a methodological framework. Int. J. Soc. Res. Methodol.; 2005; 8, pp. 19-32. [DOI: https://dx.doi.org/10.1080/1364557032000119616]

28. Tricco, A.C.; Lillie, E.; Zarin, W.; O’Brien, K.K.; Colquhoun, H.; Levac, D.; Moher, D.; Peters, M.D.J.; Horsley, T.; Weeks, L. et al. PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and Explanation. Ann. Intern. Med.; 2018; 169, pp. 467-473. [DOI: https://dx.doi.org/10.7326/M18-0850]

29. Thota, R.N.; Dias, C.B.; Abbott, K.A.; Acharya, S.H.; Garg, M.L. Curcumin alleviates postprandial glycaemic response in healthy subjects: A cross-over, randomized controlled study. Sci. Rep.; 2018; 8, 13679. [DOI: https://dx.doi.org/10.1038/s41598-018-32032-x]

30. Baum, L.; Cheung, S.K.; Mok, V.C.; Lam, L.C.; Leung, V.P.; Hui, E.; Ng, C.C.Y.; Chow, M.; Ho, P.C.; Lam, S. et al. Curcumin effects on blood lipid profile in a 6-month human study. Pharmacol. Res.; 2007; 56, pp. 509-514. [DOI: https://dx.doi.org/10.1016/j.phrs.2007.09.013]

31. DiSilvestro, R.A.; Joseph, E.; Zhao, S.; Bomser, J. Diverse effects of a low dose supplement of lipidated curcumin in healthy middle aged people. Nutr. J.; 2012; 11, 79. [DOI: https://dx.doi.org/10.1186/1475-2891-11-79]

32. Mela, D.J.; Cao, X.Z.; Dobriyal, R.; Fowler, M.I.; Lin, L.; Joshi, M.; Mulder, T.J.P.; Murray, P.G.; Peters, H.P.F.; Vermeer, M.A. et al. The effect of 8 plant extracts and combinations on post-prandial blood glucose and insulin responses in healthy adults: A randomized controlled trial. Nutr. Metab.; 2020; 17, 51. [DOI: https://dx.doi.org/10.1186/s12986-020-00471-x] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/32647531]

33. Pungcharoenkul, K.; Thongnopnua, P. Effect of different curcuminoid supplement dosages on total in vivo antioxidant capacity and cholesterol levels of healthy human subjects. Phytother. Res.; 2011; 25, pp. 1721-1726. [DOI: https://dx.doi.org/10.1002/ptr.3608] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/21796707]

34. Soni, K.; Kutian, R. Effect of oral curcumin administration on serum peroxides and cholesterol levels in human volunteers. Indian J. Physiol. Pharmacol.; 1992; 36, pp. 273-275. [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/1291482]

35. Tang, M.; Larson-Meyer, D.E.; Liebman, M. Effect of cinnamon and turmeric on urinary oxalate excretion, plasma lipids, and plasma glucose in healthy subjects. Am. J. Clin. Nutr.; 2008; 87, pp. 1262-1267. [DOI: https://dx.doi.org/10.1093/ajcn/87.5.1262] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/18469248]

36. Wickenberg, J.; Ingemansson, S.L.; Hlebowicz, J. Effects of Curcuma longa (turmeric) on postprandial plasma glucose and insulin in healthy subjects. Nutr. J.; 2010; 9, 43. [DOI: https://dx.doi.org/10.1186/1475-2891-9-43]

37. Zanzer, Y.C.; Batista, Â.G.; Björck, I.; Östman, E. Turmeric-based beverage blunted acute high fat meal-induced oxidative stress by lowering serum malondialdehyde (MDA) levels: A randomized cross-over study. Planta Med.; 2016; 82, P991. [DOI: https://dx.doi.org/10.1055/s-0036-1596975]

38. Ferguson, J.J.; Stojanovski, E.; MacDonald-Wicks, L.; Garg, M.L. Curcumin potentiates cholesterol-lowering effects of phytosterols in hypercholesterolaemic individuals. A randomised controlled trial. Metabolism; 2018; 82, pp. 22-35. [DOI: https://dx.doi.org/10.1016/j.metabol.2017.12.009]

39. Ferguson, J.J.; Wolska, A.; Remaley, A.T.; Stojanovski, E.; MacDonald-Wicks, L.; Garg, M.L. Bread enriched with phytosterols with or without curcumin modulates lipoprotein profiles in hypercholesterolaemic individuals. A randomised controlled trial. Food Funct.; 2019; 10, pp. 2515-2527. [DOI: https://dx.doi.org/10.1039/C8FO02512F]

40. Funamoto, M.; Sunagawa, Y.; Katanasaka, Y.; Miyazaki, Y.; Imaizumi, A.; Kakeya, H.; Yamakage, H.; Satoh-Asahara, N.; Komiyama, M.; Wada, H. et al. Highly absorptive curcumin reduces serum atherosclerotic low-density lipoprotein levels in patients with mild COPD. Int. J. Chronic Obstr. Pulm. Dis.; 2016; 11, pp. 2029-2034. [DOI: https://dx.doi.org/10.2147/COPD.S104490]

41. Kocher, A.; Bohnert, L.; Schiborr, C.; Frank, J. Highly bioavailable micellar curcuminoids accumulate in blood, are safe and do not reduce blood lipids and inflammation markers in moderately hyperlipidemic individuals. Mol. Nutr. Food Res.; 2016; 60, pp. 1555-1563. [DOI: https://dx.doi.org/10.1002/mnfr.201501034]

42. Mirzabeigi, P.; Mohammadpour, A.H.; Salarifar, M.; Gholami, K.; Mojtahedzadeh, M.; Javadi, M.R. The Effect of Curcumin on some of Traditional and Non-traditional Cardiovascular Risk Factors: A Pilot Randomized, Double-blind, Placebo-controlled Trial. Iran; 2015; 14, pp. 479-486.

43. Venkatesan, H. Hypolipidaemic effect of alcoholic extracts of the plants Curcuma longa and Guatteria gaumeri. Int. J. Res. Pharm. Sci.; 2019; 10, pp. 1062-1068. [DOI: https://dx.doi.org/10.26452/ijrps.v10i2.383]

44. Amirkhani, Z.; Azarbayjani, M.A.; Peeri, M.; Matin Homaei, H. Effect of combining resistance training and curcumin supplementation on lipid profile in obese women. Iran. J. Obstet. Gynecol. Infertil.; 2017; 20, pp. 24-32. [DOI: https://dx.doi.org/10.22038/IJOGI.2017.9952]

45. Blanton, C.; Gordon, B. Effect of Morning vs. Evening Turmeric Consumption on Urine Oxidative Stress Biomarkers in Obese, Middle-Aged Adults: A Feasibility Study. Int. J. Environ. Res. Public Health; 2020; 17, 4088. [DOI: https://dx.doi.org/10.3390/ijerph17114088]

46. Bupparenoo, P.; Pakchotanon, R.; Narongroeknawin, P.; Asavatanabodee, P.; Chaiamnuay, S. Effect of Curcumin on Serum Urate in Asymptomatic Hyperuricemia: A Randomized Placebo-Controlled Trial. J. Diet. Suppl.; 2020; 18, pp. 248-260. [DOI: https://dx.doi.org/10.1080/19390211.2020.1757798]

47. Campbell, M.S.; Ouyang, A.; Krishnakumar, I.M.; Charnigo, R.J.; Westgate, P.M.; Fleenor, B.S. Influence of enhanced bioavailable curcumin on obesity-associated cardiovascular disease risk factors and arterial function: A double-blinded, randomized, controlled trial. Nutrition; 2019; 62, pp. 135-139. [DOI: https://dx.doi.org/10.1016/j.nut.2019.01.002]

48. Campos-Cervantes, A.; Murillo-Ortiz, B.O.; Alvarado-Caudillo, Y.; Pérez-Vázquez, V.; RamírezEmiliano, J. Curcumin Decreases the Oxidative Damage Indexes and Increases the Adiponectin Levels in Serum of Obese Subjects. Free Radic. Biol. Med.; 2011; 51, S95. [DOI: https://dx.doi.org/10.1016/j.freeradbiomed.2011.10.463]

49. Dolati, S.; Namiranian, K.; Amerian, R.; Mansouri, S.; Arshadi, S.; Azarbayjani, M.A. The Effect of Curcumin Supplementation and Aerobic Training on Anthropometric Indices, Serum Lipid Profiles, C-Reactive Protein and Insulin Resistance in Overweight Women: A Randomized, Double-Blind, Placebo-Controlled Trial. J. Obes. Metab. Syndr.; 2020; 29, pp. 47-57. [DOI: https://dx.doi.org/10.7570/jomes19055]

50. Ganjali, S.; Sahebkar, A.; Mahdipour, E.; Jamialahmadi, K.; Torabi, S.; Akhlaghi, S.; Ferns, G.; Mohammad, S.; Parizadeh, R.; Ghayour-Mobarhan, M. Investigation of the effects of curcumin on serum cytokines in obese individuals: A randomized controlled trial. Sci. World J.; 2014; 2014, 898361. [DOI: https://dx.doi.org/10.1155/2014/898361]

51. Ismail, N.; El Dayem, S.; Hamed, M. Curcumin intake could lower serum macrophage migration inhibitory factor and monocyte chemoattractant protein-1 levels in obese subjects. Trends Med. Res.; 2016; 11, pp. 82-87. [DOI: https://dx.doi.org/10.3923/tmr.2016.82.87]

52. Ismail, N.A.; Abd El Dayem, S.M.; Salama, E.; Ragab, S.; Abd El Baky, A.N.; Ezzat, W.M. Impact of curcumin intake on gluco-insulin homeostasis, leptin and adiponectin in obese subjects. Res. J. Pharm. Biol. Chem. Sci.; 2016; 7, pp. 1891-1897.

53. Ismail, N.A.; Ragab, S.; El-Baky AN, E.A.; Hamed, M.; Ibrahim, A.A. Effect of oral curcumin administration on insulin resistance, serum resistin and fetuin-A in obese children: Randomized placebo-controlled study. Res. J. Pharm. Biol. Chem. Sci.; 2014; 5, pp. 887-896.

54. Kabaran, S.; Atakan, A. Effects of dietary intervention with or without turmeric on blood lipids and weight loss in dyslipidemic overweight/obese women. Clin. Nutr.; 2018; 37, S218. [DOI: https://dx.doi.org/10.1016/j.clnu.2018.06.1781]

55. Kawasaki, K.F.; Muroyama, K.; Murosaki, S. Effect of a combination of hot water extract of curcuma longa and curcumin on serum liver enzymes, inflammatory markers, and emotional states in healthy participants with moderately high body mass index—A randomized, double-blind, placebo-controlled clinical trial. Jpn. Pharmacol. Ther.; 2017; 45, pp. 243-252.

56. Latif, R.; Mumtaz, S.; Al Sheikh, M.H.; Chathoth, S.; Nasser Al Naimi, S. Effects of Turmeric on Cardiovascular Risk Factors, Mental Health, and Serum Homocysteine in Overweight, Obese Females. Altern. Ther. Health Med.; 2020; 21, 21.

57. Mohajer, A.; Ghayour-Mobarhan, M.; Parizadeh SM, R.; Tavallaie, S.; Rajabian, M.; Sahebkar, A. Effects of supplementation with curcuminoids on serum copper and zinc concentrations and superoxide dismutase enzyme activity in obese subjects. Trace Elem. Electrolytes; 2014; 32, pp. 16-21. [DOI: https://dx.doi.org/10.5414/TEX01363]

58. Mohamadi, A.; Sahebkar, A.H.; Iranshahi, M.; Akhlaghi, S.; Mobarhan, M.G. Curcumin effects on blood lipid profile in obese individuals. Clin. Biochem.; 2011; 44, S239. [DOI: https://dx.doi.org/10.1016/j.clinbiochem.2011.08.584]

59. Mohammadi, A.; Sahebkar, A.; Iranshahi, M.; Amini, M.; Khojasteh, R.; Ghayour-Mobarhan, M.; Ferns, G.A. Effects of supplementation with curcuminoids on dyslipidemia in obese patients: A randomized crossover trial. Phytother. Res.; 2013; 27, pp. 374-379. [DOI: https://dx.doi.org/10.1002/ptr.4715]

60. Moohebati, M.; Yazdandoust, S.; Sahebkar, A.; Mazidi, M.; Sharghi-Shahri, Z.; Ferns, G.; Ghayour-Mobarhan, M. Investigation of the effect of short-term supplementation with curcuminoids on circulating small dense low-density lipoprotein concentrations in obese dyslipidemic subjects: A randomized double-blind placebo-controlled cross-over trial. ARYA Atheroscler.; 2014; 10, pp. 280-286.

61. Nieman, D.C.; Cialdella-Kam, L.; Knab, A.M.; Shanely, R.A. Influence of red pepper spice and turmeric on inflammation and oxidative stress biomarkers in overweight females: A metabolomics approach. Plant Foods Hum. Nutr.; 2012; 67, pp. 415-421. [DOI: https://dx.doi.org/10.1007/s11130-012-0325-x]

62. Nuraiza, M.; Edwards, C.A.; Combet, E. Impact of a 3-weeks randomized double-blind cross-over study curuminoid supplementation on endotoxemia, inflammatory markers, and lipid profiles in healthy overweight and obese adults. Proc. Nutr. Soc.; 2016; 75, E160. [DOI: https://dx.doi.org/10.1017/S0029665116001750]

63. Pashine, L.; Singh, J.V.; Vaish, A.K.; Ojha, S.K.; Mahdi, A.A. Effect of turmeric (Curcuma longa) on overweight hyperlipidemic subjects: Double blind study. Indian J. Community Health; 2012; 24, pp. 113-117.

64. Sahebkar, A.; Ghayour-Mobarhan, M.; Ganjali, S.; Mahdipour, E.; Jamialahmadi, K.; Torabi, S.; Akhlaghi, S.; Ferns, G.; Parizadeh, S.M.R. Effects of curcuminoids supplementation on circulating concentrations of interleukins. Eur. J. Pharm. Sci.; 2013; 50, E164.

65. Sahebkar, A.; Mohammadi, A.; Atabati, A.; Rahiman, S.; Tavallaie, S.; Iranshahi, M.; Akhlaghi, S.; Ferns, G.A.; Ghayour-Mobarhan, M. Curcuminoids modulate pro-oxidant-antioxidant balance but not the immune response to heat shock protein 27 and oxidized LDL in obese individuals. Phytother. Res.; 2013; 27, pp. 1883-1888. [DOI: https://dx.doi.org/10.1002/ptr.4952] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/23494802]

66. Saraf-Bank, S.; Ahmadi, A.; Paknahad, Z.; Maracy, M.; Nourian, M. Effects of curcumin supplementation on markers of inflammation and oxidative stress among healthy overweight and obese girl adolescents: A randomized placebo-controlled clinical trial. Phytother. Res.; 2019; 33, pp. 2015-2022. [DOI: https://dx.doi.org/10.1002/ptr.6370]

67. Saraf-Bank, S.; Ahmadi, A.; Paknahad, Z.; Maracy, M.; Nourian, M. Effects of curcumin on cardiovascular risk factors in obese and overweight adolescent girls: A randomized clinical trial. Sao Paulo Med. J.; 2019; 137, pp. 414-422. [DOI: https://dx.doi.org/10.1590/1516-3180.2018.0454120419]

68. Uchio, R.; Muroyama, K.; Okuda-Hanafusa, C.; Kawasaki, K.; Yamamoto, Y.; Murosaki, S. Hot Water Extract of Curcuma longa L. Improves Serum Inflammatory Markers and General Health in Subjects with Overweight or Prehypertension/Mild Hypertension: A Randomized, Double-Blind, Placebo-Controlled Trial. Nutrients; 2019; 11, 1822. [DOI: https://dx.doi.org/10.3390/nu11081822]

69. Amin, F.; Islam, N.; Anila, N.; Gilani, A.H. Clinical efficacy of the co-administration of Turmeric and Black seeds (Kalongi) in metabolic syndrome—A double blind randomized controlled trial—TAK-MetS trial. Complement. Ther. Med.; 2015; 23, pp. 165-174. [DOI: https://dx.doi.org/10.1016/j.ctim.2015.01.008]

70. Chuengsamarn, S.; Rattanamongkolgul, S.; Luechapudiporn, R.; Phisalaphong, C.; Jirawatnotai, S. Curcumin extract for prevention of type 2 diabetes. Diabetes Care; 2012; 35, pp. 2121-2127. [DOI: https://dx.doi.org/10.2337/dc12-0116]

71. Di Pierro, F.; Bressan, A.; Ranaldi, D.; Rapacioli, G.; Giacomelli, L.; Bertuccioli, A. Potential role of bioavailable curcumin in weight loss and omental adipose tissue decrease: Preliminary data of a randomized, controlled trial in overweight people with metabolic syndrome. Preliminary study. Eur. Rev. Med. Pharmacol. Sci.; 2015; 19, pp. 4195-4202.

72. Ghazimoradi, M.; Saberi-Karimian, M.; Mohammadi, F.; Sahebkar, A.; Tavallaie, S.; Safarian, H.; Ferns, G.A.; Ghayour-Mobarhan, M.; Moohebati, M.; Esmaeili, H. et al. The Effects of Curcumin and Curcumin-Phospholipid Complex on the Serum Pro-oxidant-Antioxidant Balance in Subjects with Metabolic Syndrome. Phytother. Res.; 2017; 31, pp. 1715-1721. [DOI: https://dx.doi.org/10.1002/ptr.5899] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/28840615]

73. Javandoost, A.; Afshari, A.; Saberi-Karimian, M.; Sahebkar, A.; Safarian, H.; Moammeri, M.; Dizaji, B.F.; Tavalaei, S.; Ferns, G.A.; Pasdar, A. et al. The effects of curcumin and a modified curcumin formulation on serum Cholesteryl Ester Transfer Protein concentrations in patients with metabolic syndrome: A randomized, placebo-controlled clinical trial. Avicenna J.; 2018; 8, pp. 330-337.

74. Mohammadi, A.; Sadeghnia, H.R.; Saberi-Karimian, M.; Safarian, H.; Ferns, G.A.; Ghayour-Mobarhan, M.; Sahebkar, A. Effects of Curcumin on Serum Vitamin E Concentrations in Individuals with Metabolic Syndrome. Phytother. Res.; 2017; 31, pp. 657-662. [DOI: https://dx.doi.org/10.1002/ptr.5779] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/28198120]

75. Mohammadi, F.; Ghazi-Moradi, M.; Ghayour-Mobarhan, M.; Esmaeili, H.; Moohebati, M.; Saberi-Karimian, M.; Safarian, H.; Tavallaie, S.; Ferns, G.A.; Sahebkar, A. The Effects of Curcumin on Serum Heat Shock Protein 27 Antibody Titers in Patients with Metabolic Syndrome. J. Diet. Suppl.; 2018; 16, pp. 592-601. [DOI: https://dx.doi.org/10.1080/19390211.2018.1472710]

76. Osali, A. Aerobic exercise and nano-curcumin supplementation improve inflammation in elderly females with metabolic syndrome. Diabetol. Metab. Syndr.; 2020; 12, 26. [DOI: https://dx.doi.org/10.1186/s13098-020-00532-4] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/32256716]

77. Panahi, Y.; Hosseini, M.S.; Khalili, N.; Naimi, E.; Majeed, M.; Sahebkar, A. Antioxidant and anti-inflammatory effects of curcuminoid-piperine combination in subjects with metabolic syndrome: A randomized controlled trial and an updated meta-analysis. Clin. Nutr.; 2015; 34, pp. 1101-1108. [DOI: https://dx.doi.org/10.1016/j.clnu.2014.12.019] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/25618800]

78. Panahi, Y.; Hosseini, M.S.; Khalili, N.; Naimi, E.; Simental-Mendía, L.E.; Majeed, M.; Sahebkar, A. Effects of curcumin on serum cytokine concentrations in subjects with metabolic syndrome: A post-hoc analysis of a randomized controlled trial. Biomed. Pharmacother.; 2016; 82, pp. 578-582. [DOI: https://dx.doi.org/10.1016/j.biopha.2016.05.037] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/27470399]

79. Panahi, Y.; Hosseini, M.S.; Khalili, N.; Naimi, E.; Soflaei, S.S.; Majeed, M.; Sahebkar, A. Effects of supplementation with curcumin on serum adipokine concentrations: A randomized controlled trial. Nutrition; 2016; 32, pp. 1116-1122. [DOI: https://dx.doi.org/10.1016/j.nut.2016.03.018]

80. Panahi, Y.; Khalili, N.; Hosseini, M.S.; Abbasinazari, M.; Sahebkar, A. Lipid-modifying effects of adjunctive therapy with curcuminoids-piperine combination in patients with metabolic syndrome: Results of a randomized controlled trial. Complement. Ther. Med.; 2014; 22, pp. 851-857. [DOI: https://dx.doi.org/10.1016/j.ctim.2014.07.006]

81. Safarian, H.; Parizadeh, S.M.R.; Saberi-Karimain, M.; Darroudi, S.; Javandoost, A.; Mohammadi, F.; Moammeri, M.; Ferns, G.A.; Ghayour-Mobarhan, M.; Mohebati, M. The Effect of Curcumin on Serum Copper and Zinc and Zn/Cu Ratio in Individuals with Metabolic Syndrome: A Double-Blind Clinical Trial. J. Diet. Suppl.; 2018; 16, pp. 625-634. [DOI: https://dx.doi.org/10.1080/19390211.2018.1472711]

82. Sahebkar, A.; Panahi, Y.; Khalili, N. Beneficial effects of adjunctive therapy with bioavailability-enhanced curcumin in subjects with metabolic syndrome receiving low-dose atorvastatin: A randomized parallel-group trial. Eur. J. Pharm. Sci.; 2013; 50, E234.

83. Shirmohammadi, L.; Ghayour-Mobarhan, M.; Saberi-Karimian, M.; Iranshahi, M.; Tavallaie, S.; Emamian, M.; Sahebkar, A. Effect of Curcumin on Serum Cathepsin D in Patients with Metabolic Syndrome. Cardiovasc. Hematol Disord Drug Targets; 2020; 20, pp. 116-121. [DOI: https://dx.doi.org/10.2174/1871529X19666190919110652] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31538907]

84. Thota, R.N.; Rosato, J.I.; Dias, C.B.; Burrows, T.L.; Martins, R.N.; Garg, M.L. Dietary supplementation with curcumin reduce circulating levels of glycogen synthase kinase-3β and islet amyloid polypeptide in adults with high risk of type 2 diabetes and Alzheimer’s disease. Nutrients; 2020; 12, 1032. [DOI: https://dx.doi.org/10.3390/nu12041032] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/32283762]

85. Yang, Y.S.; Su, Y.F.; Yang, H.W.; Lee, Y.H.; Chou, J.I.; Ueng, K.C. Lipid-lowering effects of curcumin in patients with metabolic syndrome: A randomized, double-blind, placebo-controlled trial. Phytother. Res.; 2014; 28, pp. 1770-1777. [DOI: https://dx.doi.org/10.1002/ptr.5197] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/25131839]

86. Abbood, M.S. Hypolipidaemic and anti-inflammatory effects of curcumin versus atorvastatin in type 2 diabetic patients. Int. J. Pharm. Sci. Rev. Res.; 2018; 49, pp. 1-7.

87. Adab, Z.; Eghtesadi, S.; Vafa, M.R.; Heydari, I.; Shojaii, A.; Haqqani, H.; Arablou, T.; Eghtesadi, M. Effect of turmeric on glycemic status, lipid profile, hs-CRP, and total antioxidant capacity in hyperlipidemic type 2 diabetes mellitus patients. Phytother. Res.; 2019; 33, pp. 1173-1181. [DOI: https://dx.doi.org/10.1002/ptr.6312] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/30859660]

88. Adibian, M.; Hodaei, H.; Nikpayam, O.; Sohrab, G.; Hekmatdoost, A.; Hedayati, M. The effects of curcumin supplementation on high-sensitivity C-reactive protein, serum adiponectin, and lipid profile in patients with type 2 diabetes: A randomized, double-blind, placebo-controlled trial. Phytother. Res.; 2019; 12, 12. [DOI: https://dx.doi.org/10.1002/ptr.6328]

89. Appendino, G.; Belcaro, G.; Cornelli, U.; Luzzi, R.; Togni, S.; Dugall, M.; Cesarone, M.R.; Feragalli, B.; Ippolito, E.; Errichi, B.M. et al. Potential role of curcumin phytosome (Meriva) in controlling the evolution of diabetic microangiopathy. A pilot study. Panminerva Med.; 2011; 53, pp. 43-49.

90. Asadi, S.; Gholami, M.S.; Siassi, F.; Qorbani, M.; Khamoshian, K.; Sotoudeh, G. Nano curcumin supplementation reduced the severity of diabetic sensorimotor polyneuropathy in patients with type 2 diabetes mellitus: A randomized double-blind placebo- controlled clinical trial. Complement. Ther. Med.; 2019; 43, pp. 253-260. [DOI: https://dx.doi.org/10.1016/j.ctim.2019.02.014]

91. Chuengsamarn, S.; Rattanamongkolgul, S.; Phonrat, B.; Tungtrongchitr, R.; Jirawatnotai, S. Reduction of atherogenic risk in patients with type 2 diabetes by curcuminoid extract: A randomized controlled trial. J. Nutr. Biochem.; 2014; 25, pp. 144-150. [DOI: https://dx.doi.org/10.1016/j.jnutbio.2013.09.013]

92. Ebrahimkhani, S.; Ghavamzadeh, S.; Mehdizadeh, A. The effects of vitamin D and curcuminoids supplementation on anthropometric measurements and blood pressure in type 2 diabetic patients with coexisting hypovitaminosis D: A double-blind, placebo-controlled randomized clinical trial. Clin. Nutr. ESPEN; 2020; 37, pp. 178-186. [DOI: https://dx.doi.org/10.1016/j.clnesp.2020.02.017]

93. Funamoto, M.; Shimizu, K.; Sunagawa, Y.; Katanasaka, Y.; Miyazaki, Y.; Kakeya, H.; Yamakage, H.; Satoh-Asahara, N.; Wada, H.; Hasegawa, K. et al. Effects of Highly Absorbable Curcumin in Patients with Impaired Glucose Tolerance and Non-Insulin-Dependent Diabetes Mellitus. J. Diabetes Res.; 2019; 2019, 8208237. [DOI: https://dx.doi.org/10.1155/2019/8208237]

94. Hodaei, H.; Adibian, M.; Nikpayam, O.; Hedayati, M.; Sohrab, G. The effect of curcumin supplementation on anthropometric indices, insulin resistance and oxidative stress in patients with type 2 diabetes: A randomized, double-blind clinical trial. Diabetol. Metab. Syndr.; 2019; 11, 41. [DOI: https://dx.doi.org/10.1186/s13098-019-0437-7] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31149032]

95. Lee, M.S.; Wahlqvist, M.L.; Chou, Y.C.; Fang, W.H.; Lee, J.T.; Kuan, J.C.; Liu, H.Y.; Lu, T.M.; Xiu, L.; Hsu, C.C. et al. Turmeric improves post-prandial working memory in pre-diabetes independent of insulin. Asia Pac. J. Clin. Nutr.; 2014; 23, pp. 581-591. [DOI: https://dx.doi.org/10.6133/apjcn.2014.23.4.24] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/25516316]

96. Maithili Karpaga Selvi, N.; Sridhar, M.G.; Swaminathan, R.P.; Sripradha, R. Efficacy of Turmeric as Adjuvant Therapy in Type 2 Diabetic Patients. Indian J.; 2015; 30, pp. 180-186. [DOI: https://dx.doi.org/10.1007/s12291-014-0436-2]

97. Mokhtari, M.; Razzaghi, R.; Momen-Heravi, M. The effects of curcumin intake on wound healing and metabolic status in patients with diabetic foot ulcer: A randomized, double-blind, placebo-controlled trial. Phytother. Res.; 2020; 16, 16. [DOI: https://dx.doi.org/10.1002/ptr.6957] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/33200488]

98. Na, L.X.; Li, Y.; Pan, H.Z.; Zhou, X.L.; Sun, D.J.; Meng, M.; Li, X.-X.; Sun, C.-H. Curcuminoids exert glucose-lowering effect in type 2 diabetes by decreasing serum free fatty acids: A double-blind, placebo-controlled trial. Mol. Nutr. Food Res.; 2013; 57, pp. 1569-1577. [DOI: https://dx.doi.org/10.1002/mnfr.201200131] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/22930403]

99. Na, L.X.; Yan, B.L.; Jiang, S.; Cui, H.L.; Li, Y.; Sun, C.H. Curcuminoids Target Decreasing Serum Adipocyte-fatty Acid Binding Protein Levels in Their Glucose-lowering Effect in Patients with Type 2 Diabetes. Biomed. Environ. Sci.; 2014; 27, pp. 902-906. [DOI: https://dx.doi.org/10.3967/bes2014.127] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/25374024]

100. Neerati, P.; Devde, R.; Gangi, A.K. Evaluation of the effect of curcumin capsules on glyburide therapy in patients with type-2 diabetes mellitus. Phytother. Res.; 2014; 28, pp. 1796-1800. [DOI: https://dx.doi.org/10.1002/ptr.5201]

101. Panahi, Y.; Khalili, N.; Sahebi, E.; Namazi, S.; Atkin, S.L.; Majeed, M.; Sahebkar, A. Curcuminoids Plus Piperine Modulate Adipokines in Type 2 Diabetes Mellitus. Curr. Clin. Pharmacol.; 2017; 12, pp. 253-258. [DOI: https://dx.doi.org/10.2174/1574884713666180104095641]

102. Panahi, Y.; Khalili, N.; Sahebi, E.; Namazi, S.; Karimian, M.S.; Majeed, M.; Sahebkar, A. Antioxidant effects of curcuminoids in patients with type 2 diabetes mellitus: A randomized controlled trial. Inflammopharmacology; 2017; 25, pp. 25-31. [DOI: https://dx.doi.org/10.1007/s10787-016-0301-4] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/27928704]

103. Panahi, Y.; Khalili, N.; Sahebi, E.; Namazi, S.; Reiner, Ž.; Majeed, M.; Sahebkar, A. Curcuminoids modify lipid profile in type 2 diabetes mellitus: A randomized controlled trial. Complement. Ther. Med.; 2017; 33, pp. 1-5. [DOI: https://dx.doi.org/10.1016/j.ctim.2017.05.006] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/28735818]

104. Panahi, Y.; Khalili, N.; Sahebi, E.; Namazi, S.; Simental-Mendía, L.E.; Majeed, M.; Sahebkar, A. Effects of Curcuminoids Plus Piperine on Glycemic, Hepatic and Inflammatory Biomarkers in Patients with Type 2 Diabetes Mellitus: A Randomized Double-Blind Placebo-Controlled Trial. Drug Res.; 2018; 68, pp. 403-409. [DOI: https://dx.doi.org/10.1055/s-0044-101752] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/29458218]

105. Pingali, U.; Mateen, A. Evaluation of curcuminoids, atorvastatin and placebo on endothelial dysfunction and biomarkers in elderly diabetic patients. Basic Clin. Pharmacol. Toxicol.; 2014; 115, 261.

106. Rahimi, H.R.; Mohammadpour, A.H.; Dastani, M.; Jaafari, M.R.; Abnous, K.; Mobarhan, M.G.; Oskuee, R.K. The effect of nano-curcumin on HbA1c, fasting blood glucose, and lipid profile in diabetic subjects: A randomized clinical trial. Avicenna J.; 2016; 6, pp. 567-577.

107. Shafabakhsh, R.; Asemi, Z.; Reiner, Z.; Soleimani, A.; Aghadavod, E.; Bahmani, F. The Effects of Nano-curcumin on Metabolic Status in Patients With Diabetes on Hemodialysis, a Randomized, Double Blind, Placebo-controlled Trial. Iran. J. Kidney Dis.; 2020; 14, pp. 290-299.

108. Shafabakhsh, R.; Mobini, M.; Raygan, F.; Aghadavod, E.; Ostadmohammadi, V.; Amirani, E.; Mansournia, M.A.; Asemi, Z. Curcumin administration and the effects on psychological status and markers of inflammation and oxidative damage in patients with type 2 diabetes and coronary heart disease. Clin. Nutr. ESPEN; 2020; 40, pp. 77-82. [DOI: https://dx.doi.org/10.1016/j.clnesp.2020.09.029]

109. Sousa, D.F.; Araujo, M.F.M.; de Mello, V.D.; Damasceno, M.M.C.; Freitas, R. Cost-Effectiveness of Passion Fruit Albedo versus Turmeric in the Glycemic and Lipaemic Control of People with Type 2 Diabetes: Randomized Clinical Trial. J. Am. Coll. Nutr.; 2020; 40, pp. 679-688. [DOI: https://dx.doi.org/10.1080/07315724.2020.1823909]

110. Srinivasan, A.; Selvarajan, S.; Kamalanathan, S.; Kadhiravan, T.; Prasanna Lakshmi, N.C.; Adithan, S. Effect of Curcuma longa on vascular function in native Tamilians with type 2 diabetes mellitus: A randomized, double-blind, parallel arm, placebo-controlled trial. Phytother. Res.; 2019; 33, pp. 1898-1911. [DOI: https://dx.doi.org/10.1002/ptr.6381]

111. Steigerwalt, R.; Nebbioso, M.; Appendino, G.; Belcaro, G.; Ciammaichella, G.; Cornelli, U.; Luzzi, R.; Togni, S.; Dugall, M.; Cesarone, M.R. et al. Meriva, a lecithinized curcumin delivery system, in diabetic microangiopathy and retinopathy. Panminerva Med.; 2012; 54, pp. 11-16.

112. Thota, R.N.; Acharya, S.H.; Garg, M.L. Curcumin and/or omega-3 polyunsaturated fatty acids supplementation reduces insulin resistance and blood lipids in individuals with high risk of type 2 diabetes: A randomised controlled trial. Lipids Health Dis.; 2019; 18, 31. [DOI: https://dx.doi.org/10.1186/s12944-019-0967-x] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/30684965]

113. Usharani, P.; Mateen, A.A.; Naidu, M.U.R.; Raju, Y.S.N.; Chandra, N. Effect of NCB-02, atorvastatin and placebo on endothelial function, oxidative stress and inflammatory markers in patients with type 2 diabetes mellitus—A randomized, parallel-group, placebo-controlled, 8-week study. Drugs RD; 2008; 9, pp. 243-250. [DOI: https://dx.doi.org/10.2165/00126839-200809040-00004]

114. Yang, H.; Xu, W.; Zhou, Z.; Liu, J.; Li, X.; Chen, L.; Weng, J.; Yu, Z. Curcumin attenuates urinary excretion of albumin in type II diabetic patients with enhancing nuclear factor erythroid-derived 2-like 2 (Nrf2) system and repressing inflammatory signaling efficacies. Exp. Clin. Endocrinol. Diabetes; 2015; 123, pp. 360-367. [DOI: https://dx.doi.org/10.1055/s-0035-1545345]

115. Basu, P.; Shah, N.; Siriki, R.; Rahaman, M.; Farhat, S. Curcumin, antioxidant, and pioglitazone therapy with inclusion of vitamin e in non-alcoholic fatty liver disease: A randomized, open-label, placebo-controlled clinical prospective trial (captive). Am. J. Gastroenterol.; 2013; 108, pp. S149-S150. [DOI: https://dx.doi.org/10.14309/00000434-201310001-00505]

116. Chashmniam, S.; Mirhafez, S.R.; Dehabeh, M.; Hariri, M.; Azimi Nezhad, M.; Nobakht, M.G.B.F. A pilot study of the effect of phospholipid curcumin on serum metabolomic profile in patients with non-alcoholic fatty liver disease: A randomized, double-blind, placebo-controlled trial. Eur. J. Clin. Nutr.; 2019; 15, 15. [DOI: https://dx.doi.org/10.1038/s41430-018-0386-5] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/30647436]

117. Chirapongsathorn, S.; Jearjesdakul, J.; Sanpajit, T.; Juthaputthi, A. Curcumin trend to improve alanine transaminase (ALT) in non-alcoholic fatty liver disease (NAFLD) with abnormal ALT. J. Gastroenterol. Hepatol.; 2012; 27, pp. 231-232. [DOI: https://dx.doi.org/10.1111/jgh.12006]

118. Cicero, A.F.G.; Sahebkar, A.; Fogacci, F.; Bove, M.; Giovannini, M.; Borghi, C. Effects of phytosomal curcumin on anthropometric parameters, insulin resistance, cortisolemia and non-alcoholic fatty liver disease indices: A double-blind, placebo-controlled clinical trial. Eur. J. Nutr.; 2019; 22, 22. [DOI: https://dx.doi.org/10.1007/s00394-019-01916-7]

119. Ghaffari, A.; Rafraf, M.; Navekar, R.; Asghari-Jafarabadi, M. Effects of turmeric and chicory seed supplementation on antioxidant and inflammatory biomarkers in patients with non-alcoholic fatty liver disease (NAFLD). Adv. Integr. Med.; 2018; 5, pp. 89-95. [DOI: https://dx.doi.org/10.1016/j.aimed.2018.01.002]

120. Ghaffari, A.; Rafraf, M.; Navekar, R.; Sepehri, B.; Asghari-Jafarabadi, M.; Ghavami, S.M. Effects of turmeric on homocysteine and Fetuin-A in patients with nonalcoholic fatty liver disease: A randomized Double-Blind placebo-controlled study. Iran. Red Crescent Med. J.; 2017; 19, e43193. [DOI: https://dx.doi.org/10.5812/ircmj.43193]

121. Ghaffari, A.; Rafraf, M.; Navekar, R.; Sepehri, B.; Asghari-Jafarabadi, M.; Ghavami, S.M. Turmeric and chicory seed have beneficial effects on obesity markers and lipid profile in non-alcoholic fatty liver disease (NAFLD). Int. J. Vitam. Nutr. Res.; 2019; 89, pp. 1-10. [DOI: https://dx.doi.org/10.1024/0300-9831/a000568]

122. Hariri, M.; Gholami, A.; Mirhafez, S.R.; Bidkhori, M.; Sahebkar, A. A pilot study of the effect of curcumin on epigenetic changes and DNA damage among patients with non-alcoholic fatty liver disease: A randomized, double-blind, placebo-controlled, clinical trial. Complement. Ther. Med.; 2020; 51, 102447. [DOI: https://dx.doi.org/10.1016/j.ctim.2020.102447] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/32507446]

123. Jazayeri-Tehrani, S.A.; Rezayat, S.M.; Mansouri, S.; Qorbani, M.; Alavian, S.M.; Daneshi-Maskooni, M.; Hosseinzadeh-Attar, M.J. Nano-curcumin improves glucose indices, lipids, inflammation, and Nesfatin in overweight and obese patients with non-alcoholic fatty liver disease (NAFLD): A double-blind randomized placebo-controlled clinical trial. Nutr. Metab.; 2019; 16, 8. [DOI: https://dx.doi.org/10.1186/s12986-019-0331-1] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/30705687]

124. Mirhafez, S.R.; Farimani, A.R.; Dehhabe, M.; Bidkhori, M.; Hariri, M.; Ghouchani, B.F.; Abdollahi, F. Effect of Phytosomal Curcumin on Circulating Levels of Adiponectin and Leptin in Patients with Non-Alcoholic Fatty Liver Disease: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. J. Gastrointest. Liver Dis.; 2019; 28, pp. 183-189. [DOI: https://dx.doi.org/10.15403/jgld-179] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31204416]

125. Mirhafez, S.R.; Farimani, A.R.; Gholami, A.; Hooshmand, E.; Tavallaie, S.; Nobakht, M.G.B.F. The effect of curcumin with piperine supplementation on pro-oxidant and antioxidant balance in patients with non-alcoholic fatty liver disease: A randomized, double-blind, placebo-controlled trial. Drug Metab. Pers. Ther.; 2019; 34, 30. [DOI: https://dx.doi.org/10.1515/dmpt-2018-0040]

126. Mirhafez, S.R.; Rezai, A.; Dehabeh, M.; Nobakht, M.G.B.F.; Bidkhori, M.; Sahebkar, A.; Hariri, M. Efficacy of phytosomal curcumin among patients with non-alcoholic fatty liver disease. Int. J. Vitam. Nutr. Res.; 2019; 91, pp. 1-9. [DOI: https://dx.doi.org/10.1024/0300-9831/a000629]

127. Moradi Kelardeh, B.; Rahmati-Ahmadabad, S.; Farzanegi, P.; Helalizadeh, M.; Azarbayjani, M.A. Effects of non-linear resistance training and curcumin supplementation on the liver biochemical markers levels and structure in older women with non-alcoholic fatty liver disease. J. Bodyw. Mov. Ther.; 2020; 24, pp. 154-160. [DOI: https://dx.doi.org/10.1016/j.jbmt.2020.02.021]

128. Navekar, R.; Rafraf, M.; Ghaffari, A.; Asghari-Jafarabadi, M.; Khoshbaten, M. Turmeric Supplementation Improves Serum Glucose Indices and Leptin Levels in Patients with Nonalcoholic Fatty Liver Diseases. J. Am. Coll. Nutr.; 2017; 36, pp. 261-267. [DOI: https://dx.doi.org/10.1080/07315724.2016.1267597]

129. Panahi, Y.; Kianpour, P.; Mohtashami, R.; Jafari, R.; Simental-Mendia, L.E.; Sahebkar, A. Curcumin Lowers Serum Lipids and Uric Acid in Subjects With Nonalcoholic Fatty Liver Disease: A Randomized Controlled Trial. J. Cardiovasc. Pharmacol.; 2016; 68, pp. 223-229. [DOI: https://dx.doi.org/10.1097/FJC.0000000000000406]

130. Panahi, Y.; Kianpour, P.; Mohtashami, R.; Jafari, R.; Simental-Mendia, L.E.; Sahebkar, A. Efficacy and Safety of Phytosomal Curcumin in Non-Alcoholic Fatty Liver Disease: A Randomized Controlled Trial. Drug Res.; 2017; 67, pp. 244-251. [DOI: https://dx.doi.org/10.1055/s-0043-100019]

131. Panahi, Y.; Kianpour, P.; Mohtashami, R.; Soflaei, S.S.; Sahebkar, A. Efficacy of phospholipidated curcumin in nonalcoholic fatty liver disease: A clinical study. J. Asian Nat. Prod. Res.; 2019; 21, pp. 798-805. [DOI: https://dx.doi.org/10.1080/10286020.2018.1505873]

132. Panahi, Y.; Valizadegan, G.; Ahamdi, N.; Ganjali, S.; Majeed, M.; Sahebkar, A. Curcuminoids plus piperine improve nonalcoholic fatty liver disease: A clinical trial. J. Cell. Biochem.; 2019; 120, pp. 15989-15996. [DOI: https://dx.doi.org/10.1002/jcb.28877]

133. Rahmani, S.; Asgary, S.; Askari, G.; Keshvari, M.; Hatamipour, M.; Feizi, A.; Sahebkar, A. Treatment of Non-alcoholic Fatty Liver Disease with Curcumin: A Randomized Placebo-controlled Trial. Phytother. Res.; 2016; 30, pp. 1540-1548. [DOI: https://dx.doi.org/10.1002/ptr.5659] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/27270872]

134. Saadati, S.; Hatami, B.; Yari, Z.; Shahrbaf, M.A.; Eghtesad, S.; Mansour, A.; Poustchi, H.; Hedayati, M.; Aghajanpoor-Pasha, M.; Sadeghi, A. et al. The effects of curcumin supplementation on liver enzymes, lipid profile, glucose homeostasis, and hepatic steatosis and fibrosis in patients with non-alcoholic fatty liver disease. Eur. J. Clin. Nutr.; 2019; 73, pp. 441-449. [DOI: https://dx.doi.org/10.1038/s41430-018-0382-9] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/30610213]

135. Saadati, S.; Hekmatdoost, A.; Hatami, B.; Mansour, A.; Zahra, Z.; Hedayati, M.; Sadeghi, A. Comparing different non-invasive methods in assessment of the effects of curcumin on hepatic fibrosis in patients with non-alcoholic fatty liver disease. Gastroenterology; 2018; 11, pp. S8-S13.

136. Saadati, S.; Sadeghi, A.; Mansour, A.; Yari, Z.; Poustchi, H.; Hedayati, M.; Hatami, B.; Hekmatdoost, A. Curcumin and inflammation in non-alcoholic fatty liver disease: A randomized, placebo controlled clinical trial. BMC Gastroenterol.; 2019; 19, 133. [DOI: https://dx.doi.org/10.1186/s12876-019-1055-4]

137. Saberi-Karimian, M.; Keshvari, M.; Ghayour-Mobarhan, M.; Salehizadeh, L.; Rahmani, S.; Behnam, B.; Jamialahmadi, T.; Asgary, S.; Sahebkar, A. Effects of curcuminoids on inflammatory status in patients with nonalcoholic fatty liver disease: A randomized controlled trial. Complement. Ther. Med.; 2020; 49, 6. [DOI: https://dx.doi.org/10.1016/j.ctim.2020.102322]

138. Selmanovic, S.; Beganlic, A.; Salihefendic, N.; Ljuca, F.; Softic, A.; Smajic, E. Therapeutic Effects of Curcumin on Ultrasonic Morphological Characteristics of Liver in Patients with Metabolic Syndrome. Acta Inform. Med.; 2017; 25, pp. 169-174. [DOI: https://dx.doi.org/10.5455/aim.2017.25.169-174]

139. Lindenmeyer, C.C.; McCullough, A.J. The Natural History of Nonalcoholic Fatty Liver Disease—An Evolving View. Clin. Liver Dis.; 2018; 22, pp. 11-21. [DOI: https://dx.doi.org/10.1016/j.cld.2017.08.003]

140. Atabaki, M.; Shariati-Sarabi, Z.; Tavakkol-Afshari, J.; Mohammadi, M. Significant immunomodulatory properties of curcumin in patients with osteoarthritis; a successful clinical trial in Iran. Int. Immunopharmacol.; 2020; 85, 106607. [DOI: https://dx.doi.org/10.1016/j.intimp.2020.106607]

141. Belcaro, G.; Cesarone, M.R.; Dugall, M.; Pellegrini, L.; Ledda, A.; Grossi, M.G.; Togni, S.; Appendino, G. Efficacy and safety of Meriva, a curcumin-phosphatidylcholine complex, during extended administration in osteoarthritis patients. Altern. Med. Rev.; 2010; 15, pp. 337-344.

142. Calderon-Perez, L.; Llaurado, E.; Companys, J.; Pla-Paga, L.; Boque, N.; Puiggros, F.; Valls, R.M.; Pedret, A.; Llabres, J.M.; Arola, L. et al. Acute Effects of Turmeric Extracts on Knee Joint Pain: A Pilot, Randomized Controlled Trial. J. Med. Food; 2020; 29, 29. [DOI: https://dx.doi.org/10.1089/jmf.2020.0074]

143. Di Pierro, F.; Zacconi, P.; Bertuccioli, A.; Togni, S.; Eggenhoffner, R.; Giacomelli, L.; Scaltrini, S. A naturally-inspired, curcumin-based lecithin formulation (Meriva formulated as the finished product Algocur) alleviates the osteo-muscular pain conditions in rugby players. Eur. Rev. Med. Pharmacol. Sci.; 2017; 21, pp. 4935-4940.

144. Gupte, P.A.; Giramkar, S.A.; Harke, S.M.; Kulkarni, S.K.; Deshmukh, A.P.; Hingorani, L.L.; Mahajan, M.P.; Bhalerao, S.S. Evaluation of the efficacy and safety of Capsule Longvida^® Optimized Curcumin (solid lipid curcumin particles) in knee osteoarthritis: A pilot clinical study. J. Inflamm. Res.; 2019; 12, pp. 145-152. [DOI: https://dx.doi.org/10.2147/JIR.S205390]

145. Haroyan, A.; Mukuchyan, V.; Mkrtchyan, N.; Minasyan, N.; Gasparyan, S.; Sargsyan, A.; Narimanyan, M.; Hovhannisyan, A. Efficacy and safety of curcumin and its combination with boswellic acid in osteoarthritis: A comparative, randomized, double-blind, placebo-controlled study. BMC Complement. Altern. Med.; 2018; 18, 7. [DOI: https://dx.doi.org/10.1186/s12906-017-2062-z] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/29316908]

146. Hashemzadeh, K.; Davoudian, N.; Jaafari, M.R.; Mirfeizi, Z. The Effect of Nanocurcumin in Improvement of Knee Osteoarthritis: A Randomized Clinical Trial. Curr. Rheumatol. Rev.; 2020; 16, pp. 158-164. [DOI: https://dx.doi.org/10.2174/1874471013666191223152658]

147. Henrotin, Y.; Gharbi, M.; Dierckxsens, Y.; Priem, F.; Marty, M.; Seidel, L.; Albert, A.; Heuse, E.; Bonnet, V.; Castermans, C. Decrease of a specific biomarker of collagen degradation in osteoarthritis, Coll2-1, by treatment with highly bioavailable curcumin during an exploratory clinical trial. BMC Complement. Altern. Med.; 2014; 14, 159. [DOI: https://dx.doi.org/10.1186/1472-6882-14-159]

148. Henrotin, Y.; Malaise, M.; Wittoek, R.; de Vlam, K.; Brasseur, J.P.; Luyten, F.P.; Jiangang, Q.; Van den Berghe, M.; Uhoda, R.; Bentin, J. et al. Bio-optimized Curcuma longa extract is efficient on knee osteoarthritis pain: A double-blind multicenter randomized placebo controlled three-arm study. Arthritis Res. Ther.; 2019; 21, 179. [DOI: https://dx.doi.org/10.1186/s13075-019-1960-5] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31351488]

149. Kertia, N.; Ahmad Husain Asdie, A.; Wasilah Rochmah, W.; Marsetyawan, M. Anti-inflammatory activities and the safety of curcuminoid compared to diclofenac sodium for the treatment of osteoarthritis. Int. J. Rheum. Dis.; 2013; 16, 37.

150. Kertia, N.; Asdie, A.H.; Rochmah, W. Ability of curcuminoid compared to diclofenac sodium in reducing the secretion of cycloxygenase-2 enzyme by synovial fluid’s monocytes of patients with osteoarthritis. Acta Med.; 2012; 44, pp. 105-113.

151. Khanna, A.; Das, S.S.; Smina, T.P.; Thomas, J.V.; Kunnumakkara, A.B.; Maliakel, B.; Krishnakumar, I.M.; Mohanan, R. Curcumagalactomannoside/Glucosamine Combination Improved Joint Health Among Osteoarthritic Subjects as Compared to Chondroitin Sulfate/Glucosamine: Double-Blinded, Randomized Controlled Study. J. Altern. Complement. Med.; 2020; 26, pp. 945-955. [DOI: https://dx.doi.org/10.1089/acm.2020.0128]

152. Kuptniratsaikul, V.; Dajpratham, P.; Taechaarpornkul, W.; Buntragulpoontawee, M.; Lukkanapichonchut, P.; Chootip, C.; Saengsuwan, J.; Tantayakom, K.; Laongpech, S. Efficacy and safety of Curcuma domestica extracts compared with ibuprofen in patients with knee osteoarthritis: A multicenter study. Clin. Interv. Aging; 2014; 9, pp. 451-458. [DOI: https://dx.doi.org/10.2147/CIA.S58535]

153. Kuptniratsaikul, V.; Thanakhumtorn, S.; Chinswangwatanakul, P.; Wattanamongkonsil, L.; Thamlikitkul, V. Efficacy and safety of Curcuma domestica extracts in patients with knee osteoarthritis. J. Altern. Complement. Med.; 2009; 15, pp. 891-897. [DOI: https://dx.doi.org/10.1089/acm.2008.0186] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/19678780]

154. Madhu, K.; Chanda, K.; Saji, M.J. Safety and efficacy of Curcuma longa extract in the treatment of painful knee osteoarthritis: A randomized placebo-controlled trial. Inflammopharmacology; 2013; 21, pp. 129-136. [DOI: https://dx.doi.org/10.1007/s10787-012-0163-3] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/23242572]

155. Nakagawa, Y.; Mukai, S.; Yamada, S.; Matsuoka, M.; Tarumi, E.; Hashimoto, T.; Tamura, C.; Imaizumi, A.; Nishihira, J.; Nakamura, T. Short-term effects of highly-bioavailable curcumin for treating knee osteoarthritis: A randomized, double-blind, placebo-controlled prospective study. J. Orthop. Sci.; 2014; 19, pp. 933-939. [DOI: https://dx.doi.org/10.1007/s00776-014-0633-0]

156. Nakagawa, Y.; Mukai, S.; Yamada, S.; Murata, S.; Yabumoto, H.; Maeda, T.; Akamatsu, S. The Efficacy and Safety of Highly-Bioavailable Curcumin for Treating Knee Osteoarthritis: A 6-Month Open-Labeled Prospective Study. Clin. Med. Insights Arthritis Musculoskelet. Disord.; 2020; 13, 1179544120948471. [DOI: https://dx.doi.org/10.1177/1179544120948471] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/32848491]

157. Panahi, Y.; Alishiri, G.H.; Parvin, S.; Sahebkar, A. Mitigation of Systemic Oxidative Stress by Curcuminoids in Osteoarthritis: Results of a Randomized Controlled Trial. J. Diet. Suppl.; 2016; 13, pp. 209-220. [DOI: https://dx.doi.org/10.3109/19390211.2015.1008611]

158. Panahi, Y.; Rahimnia, A.R.; Sharafi, M.; Alishiri, G.; Saburi, A.; Sahebkar, A. Curcuminoid treatment for knee osteoarthritis: A randomized double-blind placebo-controlled trial. Phytother. Res.; 2014; 28, pp. 1625-1631. [DOI: https://dx.doi.org/10.1002/ptr.5174]

159. Panda, S.K.; Nirvanashetty, S.; Parachur, V.A.; Mohanty, N.; Swain, T. A Randomized, Double Blind, Placebo Controlled, Parallel-Group Study to Evaluate the Safety and Efficacy of Curene versus Placebo in Reducing Symptoms of Knee OA. Biomed. Res. Int.; 2018; 2018, 5291945. [DOI: https://dx.doi.org/10.1155/2018/5291945]

160. Pinsornsak, P.; Niempoog, S. The efficacy of Curcuma Longa, L. extract as an adjuvant therapy in primary knee osteoarthritis: A randomized control trial. J. Med. Assoc. Thai; 2012; 95, (Suppl. S1), pp. S51-S58.

161. Rahimnia, A.R.; Panahi, Y.; Alishiri, G.; Sharafi, M.; Sahebkar, A. Impact of Supplementation with Curcuminoids on Systemic Inflammation in Patients with Knee Osteoarthritis: Findings from a Randomized Double-Blind Placebo-Controlled Trial. Drug Res.; 2015; 65, pp. 521-525. [DOI: https://dx.doi.org/10.1055/s-0034-1384536]

162. Raj, J.P.; Venkatachalam, S.; Racha, P.; Bhaskaran, S.; Amaravati, R.S. Effect of Turmacin supplementation on joint discomfort and functional outcome among healthy participants—A randomized placebo-controlled trial. Complement. Ther. Med.; 2020; 53, 102522. [DOI: https://dx.doi.org/10.1016/j.ctim.2020.102522] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/33066856]

163. Ross, S.M. Turmeric (Curcuma longa): Effects of Curcuma longa Extracts Compared With Ibuprofen for Reduction of Pain and Functional Improvement in Patients With Knee Osteoarthritis. Holist. Nurs. Pract.; 2016; 30, pp. 183-186. [DOI: https://dx.doi.org/10.1097/HNP.0000000000000152]

164. Sahebkar, A.H.; Panahi, Y.; Sabouri, A.; Rahimnia, A.; Sharafi, M.; Alishiri, G.H. Efficacy and safety of supplementation with curcuminoids in the treatment of patients with osteoarthritis: A randomized controlled trial. Avicenna J.; 2015; 5, pp. 15-16.

165. Saksena, A.K.; Srivastava, S.; Khattri, S.; Kumar, S. Efficacy of Curcuma longa in osteoarthritis: Association of IL-1beta, IL-10 and MMP-9 with severity of disease. J. Immunol.; 2016; 196, 124-13. [DOI: https://dx.doi.org/10.4049/jimmunol.196.Supp.124.13]

166. Shep, D.; Khanwelkar, C.; Gade, P.; Karad, S. Safety and efficacy of curcumin versus diclofenac in knee osteoarthritis: A randomized open-label parallel-arm study. Trials; 2019; 20, 214. [DOI: https://dx.doi.org/10.1186/s13063-019-3327-2]

167. Shep, D.; Khanwelkar, C.; Gade, P.; Karad, S. Efficacy and safety of combination of curcuminoid complex and diclofenac versus diclofenac in knee osteoarthritis: A randomized trial. Medicine; 2020; 99, e19723. [DOI: https://dx.doi.org/10.1097/MD.0000000000019723]

168. Srivastava, S.; Saksena, A.K.; Khattri, S.; Kumar, S.; Dagur, R.S. Curcuma longa extract reduces inflammatory and oxidative stress biomarkers in osteoarthritis of knee: A four-month, double-blind, randomized, placebo-controlled trial. Inflammopharmacology; 2016; 24, pp. 377-388. [DOI: https://dx.doi.org/10.1007/s10787-016-0289-9]

169. Thomas, J.V.; Smina, T.P.; Khanna, A.; Kunnumakkara, A.B.; Maliakel, B.; Mohanan, R.; Krishnakumar, I.M. Influence of a low-dose supplementation of curcumagalactomannoside complex (CurQfen) in knee osteoarthritis: A randomized, open-labeled, active-controlled clinical trial. Phytother. Res.; 2020; 18, 18. [DOI: https://dx.doi.org/10.1002/ptr.6907] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/33210408]

170. Wang, Z.; Jones, G.; Winzenberg, T.; Cai, G.; Laslett, L.L.; Aitken, D.; Hopper, I.; Singh, A.; Jones, R.; Fripp, J. et al. Effectiveness of Curcuma longa Extract for the Treatment of Symptoms and Effusion-Synovitis of Knee Osteoarthritis: A Randomized Trial. Ann. Intern. Med.; 2020; 173, pp. 861-869. [DOI: https://dx.doi.org/10.7326/M20-0990]

171. Abbas, A.A.; Ali, A.H.; Ali, H.F.A.; Abbas, R.A. Effect of dietary supplement (Turmeric) in the level of concentration of lactic acid and lactic acid dehydrogenase in the players of the University of Babylon Futsal. Indian J. Public Health Res. Dev.; 2020; 11, pp. 1323-1327.

172. Ali, R.H.; Ray, H.R.D. The Effect of Turmeric Consumption to VO(2)Max and Lactate Threshold. 1st Annual Applied Science and Engineering Conference; Abdullah, A.G.; Nandiyanto, A.B.D.; Danuwijaya, A.A. IOP Publishing: Bristol, UK, 2017; Volume 180.

173. Amalraj, A.; Divya, C.; Gopi, S. The Effects of Bioavailable Curcumin (Cureit) on Delayed Onset Muscle Soreness Induced By Eccentric Continuous Exercise: A Randomized, Placebo-Controlled, Double-Blind Clinical Study. J. Med. Food; 2020; 23, pp. 545-553. [DOI: https://dx.doi.org/10.1089/jmf.2019.4533]

174. Basham, S.A.; Waldman, H.S.; Krings, B.M.; Lamberth, J.; Smith, J.W.; McAllister, M.J. Effect of Curcumin Supplementation on Exercise-Induced Oxidative Stress, Inflammation, Muscle Damage, and Muscle Soreness. J. Diet. Suppl.; 2019; 17, pp. 401-414. [DOI: https://dx.doi.org/10.1080/19390211.2019.1604604]

175. Cardaci, T.D.; Machek, S.B.; Wilburn, D.T.; Hwang, P.S.; Willoughby, D.S. Ubiquitin Proteasome System Activity is Suppressed by Curcumin following Exercise-Induced Muscle Damage in Human Skeletal Muscle. J. Am. Coll. Nutr.; 2020; 40, pp. 401-411. [DOI: https://dx.doi.org/10.1080/07315724.2020.1783721]

176. Drobnic, F.; Riera, J.; Appendino, G.; Togni, S.; Franceschi, F.; Valle, X.; Pons, A.; Tur, J. Reduction of delayed onset muscle soreness by a novel curcumin delivery system (Meriva): A randomised, placebo-controlled trial. J. Int. Soc. Sport. Nutr.; 2014; 11, 31. [DOI: https://dx.doi.org/10.1186/1550-2783-11-31] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/24982601]

177. Faria, F.R.; Gomes, A.C.; Antunes, A.; Rezende, K.R.; Pimentel, G.D.; Oliveira, C.L.P.; Antunes, B.M.; Lira, F.S.; Aoki, M.S.; Mota, J.F. Effects of turmeric extract supplementation on inflammation and muscle damage after a half-marathon race: A randomized, double-blind, placebo-controlled trial. Eur. J. Appl. Physiol.; 2020; 120, pp. 1531-1540. [DOI: https://dx.doi.org/10.1007/s00421-020-04385-7]

178. Franceschi, F.; Feregalli, B.; Togni, S.; Cornelli, U.; Giacomelli, L.; Eggenhoffner, R.; Belcaro, G. A novel phospholipid delivery system of curcumin (Meriva) preserves muscular mass in healthy aging subjects. Eur. Rev. Med. Pharmacol. Sci.; 2016; 20, pp. 762-766. [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/26957282]

179. Gerchman, A.; Hillman, A.; O’Hora, E. The Effect of Curcumin on Inflammation and Exercise Induced Muscle Damage in Healthy Adults. Med. Sci. Sport. Exerc.; 2018; 50, 721. [DOI: https://dx.doi.org/10.1249/01.mss.0000538377.63178.7e]

180. Herrick, L.P.; Goh, J.; Menke, W.; Campbell, M.S.; Fleenor, B.S.; Abel, M.G.; Bergstrom, H.C. Effects of Curcumin and Fenugreek Soluble Fiber on the Physical Working Capacity at the Fatigue Threshold, Peak Oxygen Consumption, and Time to Exhaustion. J. Strength Cond. Res.; 2020; 34, pp. 3346-3355. [DOI: https://dx.doi.org/10.1519/JSC.0000000000003852]

181. Jager, R.; Caldwell, A.R.; Sanders, E.; Mitchell, J.B.; Rogers, J.; Purpura, M.; Oliver, J.M. Curcumin reduces muscle damage and soreness following muscle-damaging exercise. FASEB J.; 2017; 31, lb766.

182. Jager, R.; Purpura, M.; Kerksick, C.M. Eight Weeks of a High Dose of Curcumin Supplementation May Attenuate Performance Decrements Following Muscle-Damaging Exercise. Nutrients; 2019; 11, 1692. [DOI: https://dx.doi.org/10.3390/nu11071692] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31340534]

183. Mallard, A.R.; Briskey, D.; Richards, B.A.; Rao, A. Curcumin Improves Delayed Onset Muscle Soreness and Postexercise Lactate Accumulation. J. Diet. Suppl.; 2020; 18, pp. 531-542. [DOI: https://dx.doi.org/10.1080/19390211.2020.1796885]

184. McAllister, M.J.; Basham, S.A.; Waldman, H.S.; Smith, J.W.; Butawan, M.B.; Bloomer, R.J. Effects of Curcumin on the Oxidative Stress Response to a Dual Stress Challenge in Trained Men. J. Diet. Suppl.; 2018; 17, pp. 261-272. [DOI: https://dx.doi.org/10.1080/19390211.2018.1515142]

185. McFarlin, B.K.; Venable, A.S.; Henning, A.L.; Sampson, J.N.; Pennel, K.; Vingren, J.L.; Hill, D.W. Reduced inflammatory and muscle damage biomarkers following oral supplementation with bioavailable curcumin. BBA Clin.; 2016; 5, pp. 72-78. [DOI: https://dx.doi.org/10.1016/j.bbacli.2016.02.003]

186. Nicol, L.M.; Rowlands, D.S.; Fazakerly, R.; Kellett, J. Curcumin supplementation likely attenuates delayed onset muscle soreness (DOMS). Eur. J. Appl. Physiol.; 2015; 115, pp. 1769-1777. [DOI: https://dx.doi.org/10.1007/s00421-015-3152-6]

187. Sciberras, J.N.; Galloway, S.D.; Fenech, A.; Grech, G.; Farrugia, C.; Duca, D.; Mifsud, J. The effect of turmeric (Curcumin) supplementation on cytokine and inflammatory marker responses following 2 hours of endurance cycling. J. Int. Soc. Sport. Nutr.; 2015; 12, 5. [DOI: https://dx.doi.org/10.1186/s12970-014-0066-3] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/25628521]

188. Takahashi, M.; Suzuki, K.; Kim, H.K.; Otsuka, Y.; Imaizumi, A.; Miyashita, M.; Sakamoto, S. Effects of curcumin supplementation on exercise-induced oxidative stress in humans. Int. J. Sport. Med.; 2014; 35, pp. 469-475. [DOI: https://dx.doi.org/10.1055/s-0033-1357185] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/24165958]

189. Tanabe, Y.; Chino, K.; Akazawa, N.; Imaizumi, A.; Ozawa, H.; Sumi, Y.; Maeda, S.; Takahashi, H. Curcumin intake after eccentric exercise effectively reduces muscle damage and enables faster recovery. Int. J. Sport Nutr. Exerc. Metab.; 2018; 28, pp. S1-S4. [DOI: https://dx.doi.org/10.1123/ijsnem.2018-0144]

190. Tanabe, Y.; Chino, K.; Ohnishi, T.; Ozawa, H.; Sagayama, H.; Maeda, S.; Takahashi, H. Effects of oral curcumin ingested before or after eccentric exercise on markers of muscle damage and inflammation. Scand. J. Med. Sci. Sport.; 2019; 29, pp. 524-534. [DOI: https://dx.doi.org/10.1111/sms.13373] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/30566760]

191. Tanabe, Y.; Chino, K.; Sagayama, H.; Lee, H.J.; Ozawa, H.; Maeda, S.; Takahashi, H. Effective Timing of Curcumin Ingestion to Attenuate Eccentric Exercise-Induced Muscle Soreness in Men. J. Nutr. Sci. Vitaminol.; 2019; 65, pp. 82-89. [DOI: https://dx.doi.org/10.3177/jnsv.65.82]

192. Tanabe, Y.; Maeda, S.; Akazawa, N.; Zempo-Miyaki, A.; Choi, Y.; Ra, S.G.; Imaizumi, A.; Otsuka, Y.; Nosaka, K. Attenuation of indirect markers of eccentric exercise-induced muscle damage by curcumin. Eur. J. Appl. Physiol.; 2015; 115, pp. 1949-1957. [DOI: https://dx.doi.org/10.1007/s00421-015-3170-4]

193. Varma, K.; Amalraj, A.; Divya, C.; Gopi, S. The Efficacy of the Novel Bioavailable Curcumin (Cureit) in the Management of Sarcopenia in Healthy Elderly Subjects: A Randomized, Placebo-Controlled, Double-Blind Clinical Study. J. Med. Food; 2020; 24, pp. 40-49. [DOI: https://dx.doi.org/10.1089/jmf.2020.4778]

194. Wang, I.L.; Hsiao, C.Y.; Li, Y.H.; Meng, F.B.; Huang, C.C.; Chen, Y.M. Nanobubbles Water Curcumin Extract Reduces Injury Risks on Drop Jumps in Women: A Pilot Study. Evid. Based Complement. Altern. Med.; 2019; 2019, 8647587. [DOI: https://dx.doi.org/10.1155/2019/8647587]

195. Amalraj, A.; Varma, K.; Jacob, J.; Divya, C.; Kunnumakkara, A.B.; Stohs, S.J.; Gopi, S. A Novel Highly Bioavailable Curcumin Formulation Improves Symptoms and Diagnostic Indicators in Rheumatoid Arthritis Patients: A Randomized, Double-Blind, Placebo-Controlled, Two-Dose, Three-Arm, and Parallel-Group Study. J. Med. Food; 2017; 20, pp. 1022-1030. [DOI: https://dx.doi.org/10.1089/jmf.2017.3930]

196. Chandran, B.; Goel, A. A randomized, pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis. Phytother. Res.; 2012; 26, pp. 1719-1725. [DOI: https://dx.doi.org/10.1002/ptr.4639] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/22407780]

197. Jacob, J.; Amalraj, A.; Raj, K.K.J.; Divya, C.; Kunnumakkara, A.B.; Gopi, S. A novel bioavailable hydrogenated curcuminoids formulation (CuroWhite TM) improves symptoms and diagnostic indicators in rheumatoid arthritis patients–A randomized, double blind and placebo controlled study. J. Tradit. Complement. Med.; 2019; 9, pp. 346-352. [DOI: https://dx.doi.org/10.1016/j.jtcme.2018.06.001]

198. Javadi, M.; Khadem Haghighian, H.; Goodarzy, S.; Abbasi, M.; Nassiri-Asl, M. Effect of curcumin nanomicelle on the clinical symptoms of patients with rheumatoid arthritis: A randomized, double-blind, controlled trial. Int. J. Rheum. Dis.; 2019; 22, pp. 1857-1862. [DOI: https://dx.doi.org/10.1111/1756-185X.13688]

199. Schulman, R. Special Curcumin Extract from Turmeric Shows Promise in Rheumatoid Arthritis Patients in Pilot Trial. HerbalGram; 2012; 95, 33.Available online: https://www.herbalgram.org/resources/herbalgram/issues/95/table-of-contents/hg95-resrvw-curcumin/ (accessed on 22 February 2023).

200. Wahono, C.S.; Kalim, H.; Saveria, I.; Setyorini, C.D.; Wahyuni, Z.; Dimpudus, R.A.; Kusworini, H. Effect of curcumin and vitamin d on disease activity, fatigue, and cytokine profile in systemic lupus erythematosus patients with deficiency vitamin d. Lupus Sci. Med.; 2017; 4, pp. A38-A39. [DOI: https://dx.doi.org/10.1136/lupus-2017-000215.92]

201. Wahono, C.S.; Saveria, I.; Setyorini, C.D.; Wahyuni, Z.D.; Handono, K.; Kalim, H. The effect of adding curcumin on vitamin D3 supplementation on cytokines balance, in sle patients with hypovitamin D. Lupus Sci. Med.; 2017; 4, A120. [DOI: https://dx.doi.org/10.1136/lupus-2017-000215.258]

202. Wahono, C.S.; Susianti, H.; Wahyuni, Z.D.; Saveria, I.; Setyorini, C.D.; Handono, K.; Kalim, H. The effect of adding curcumin on vitamin D3 supplementation on anti-DSDNA levels and proteinuria, in SLE patients with hypovitamin D. Lupus Sci. Med.; 2017; 4, pp. A119-A120. [DOI: https://dx.doi.org/10.1136/lupus-2017-000215.257]

203. Ahmadi, M.; Hajialilo, M.; Dolati, S.; Eghbal-Fard, S.; Heydarlou, H.; Ghaebi, M.; Ghassembaglou, A.; Aghebati-Maleki, L.; Samadi Kafil, H.; Kamrani, A. et al. The effects of nanocurcumin on Treg cell responses and treatment of ankylosing spondylitis patients: A randomized, double-blind, placebo-controlled clinical trial. J. Cell. Biochem.; 2019; 09, 09. [DOI: https://dx.doi.org/10.1002/jcb.28901] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31074089]

204. Hatefi, M.; Ahmadi, M.R.H.; Rahmani, A.; Dastjerdi, M.M.; Asadollahi, K. Effects of Curcumin on Bone Loss and Biochemical Markers of Bone Turnover in Patients with Spinal Cord Injury. World Neurosurg.; 2018; 114, pp. e785-e791. [DOI: https://dx.doi.org/10.1016/j.wneu.2018.03.081] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/29567290]

205. Khanizadeh, F.; Rahmani, A.; Asadollahi, K.; Ahmadi, M.R.H. Combination therapy of curcumin and alendronate modulates bone turnover markers and enhances bone mineral density in postmenopausal women with osteoporosis. Arch. Endocrinol. Metab.; 2018; 62, pp. 438-445. [DOI: https://dx.doi.org/10.20945/2359-3997000000060] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/30304108]

206. Riva, A.; Togni, S.; Giacomelli, L.; Franceschi, F.; Eggenhoffner, R.; Feragalli, B.; Belcaro, G.; Cacchio, M.; Shu, H.; Dugall, M. Effects of a curcumin-based supplementation in asymptomatic subjects with low bone density: A preliminary 24-week supplement study. Eur. Rev. Med. Pharmacol. Sci.; 2017; 21, pp. 1684-1689.

207. Abdolahi, M.; Jafarieh, A.; Sarraf, P.; Sedighiyan, M.; Yousefi, A.; Tafakhori, A.; Abdollahi, H.; Salehinia, F.; Djalali, M. The Neuromodulatory Effects of omega-3 Fatty Acids and Nano-Curcumin on the COX-2/iNOS Network in Migraines: A Clinical Trial Study from Gene Expression to Clinical Symptoms. Endocr. Metab. Immune Disord. Drug Targets; 2019; 19, 12. [DOI: https://dx.doi.org/10.2174/1871530319666190212170140]

208. Abdolahi, M.; Sarraf, P.; Javanbakht, M.H.; Honarvar, N.M.; Hatami, M.; Soveyd, N.; Tafakhori, A.; Sedighiyan, M.; Djalali, M.; Jafarieh, A. et al. A Novel Combination of omega-3 Fatty Acids and Nano-Curcumin Modulates Interleukin-6 Gene Expression and High Sensitivity C-reactive Protein Serum Levels in Patients with Migraine: A Randomized Clinical Trial Study. CNS Neurol. Disord. Drug Targets; 2018; 17, pp. 430-438. [DOI: https://dx.doi.org/10.2174/1871527317666180625101643]

209. Abdolahi, M.; Tafakhori, A.; Togha, M.; Okhovat, A.A.; Siassi, F.; Eshraghian, M.R.; Sedighiyan, M.; Djalali, M.; Mohammadzadeh Honarvar, N.; Djalali, M. The synergistic effects of omega-3 fatty acids and nano-curcumin supplementation on tumor necrosis factor (TNF)-alpha gene expression and serum level in migraine patients. Immunogenetics; 2017; 69, pp. 371-378. [DOI: https://dx.doi.org/10.1007/s00251-017-0992-8]

210. Djalali, M.; Abdolahi, M.; Hosseini, R.; Miraghajani, M.; Mohammadi, H.; Djalali, M. The effects of nano-curcumin supplementation on Th1/Th17 balance in migraine patients: A randomized controlled clinical trial. Complement. Ther. Clin. Pract.; 2020; 41, 101256. [DOI: https://dx.doi.org/10.1016/j.ctcp.2020.101256]

211. Djalali, M.; Djalali, M.; Abdolahi, M.; Mohammadi, H.; Heidari, H.; Hosseini, S.; Sadeghizadeh, M. The Effect of Nano-Curcumin Supplementation on Pentraxin 3 Gene Expression and Serum Level in Migraine Patients. Rep. Biochem. Mol. Biol.; 2020; 9, pp. 1-7. [DOI: https://dx.doi.org/10.29252/rbmb.9.1.1]

212. Honarvar, N.M.; Soveid, N.; Abdolahi, M.; Djalali, M.; Hatami, M.; Karzar, N.H. Anti-Neuroinflammatory Properties of n-3 Fatty Acids and Nano-Curcumin on Migraine Patients, from Cellular to Clinical Insight: A Randomized, Double Blind, and Placebo-Controlled Trial. Endocr. Metab. Immune Disord. Drug Targets; 2020; 29, 29. [DOI: https://dx.doi.org/10.2174/1871530320666200729144430]

213. Chiu, S.S.; Woodbury-Farina, M.; Terpstra, K.; Badmaev, V.; Cernovsky, Z.; Jirui Hou, J.; Raheb, H.; Husni, M.; Copen, J.; Shad, M. et al. Translating curry extract to novel therapeutic approach in schizophrenia: The emerging role of epigenetics signaling. Planta Med. Int. Open; 2018; 5, DM02. [DOI: https://dx.doi.org/10.1055/s-0038-1644931]

214. Kucukgoncu, S.; Guloksuz, S.; Tek, C. Effects of Curcumin on Cognitive Functioning and Inflammatory State in Schizophrenia: A Double-Blind, Placebo-Controlled Pilot Trial. J. Clin. Psychopharmacol.; 2019; 39, pp. 182-184. [DOI: https://dx.doi.org/10.1097/JCP.0000000000001012]

215. Miodownik, C.; Lerner, V.; Kudkaeva, N.; Lerner, P.P.; Pashinian, A.; Bersudsky, Y.; Eliyahu, R.; Kreinin, A.; Bergman, J. Curcumin as Add-On to Antipsychotic Treatment in Patients With Chronic Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled Study. Clin. Neuropharmacol.; 2019; 30, 30. [DOI: https://dx.doi.org/10.1097/WNF.0000000000000344]

216. Wynn, J.K.; Green, M.F.; Hellemann, G.; Karunaratne, K.; Davis, M.C.; Marder, S.R. The effects of curcumin on brain-derived neurotrophic factor and cognition in schizophrenia: A randomized controlled study. Schizophr Res.; 2018; 195, pp. 572-573. [DOI: https://dx.doi.org/10.1016/j.schres.2017.09.046]

217. Ahmadi, M.; Agah, E.; Nafissi, S.; Jaafari, M.R.; Harirchian, M.H.; Sarraf, P.; Faghihi-Kashani, S.; Hosseini, S.J.; Ghoreishi, A.; Aghamollaii, V. et al. Safety and Efficacy of Nanocurcumin as Add-On Therapy to Riluzole in Patients With Amyotrophic Lateral Sclerosis: A Pilot Randomized Clinical Trial. Neurother; 2018; 15, pp. 430-438. [DOI: https://dx.doi.org/10.1007/s13311-018-0606-7]

218. Caldarazzo Ienco, E.; Bisordi, C.; Chico, L.; Lo Gerfo, A.; Fabbrini, M.; Rossi, M.; Petrozzi, L.; Rocchi, A.; Siciliano, G. High bioavailability curcumin and motor neuron degeneration: Results of a pilot therapeutic trial in amyotrophic lateral sclerosis. Amyotroph. Lateral Scler. Front. Degener.; 2016; 17, 236. [DOI: https://dx.doi.org/10.1080/21678421.2016.1232064/001]

219. Chico, L.; Ienco, E.C.; Bisordi, C.; Lo Gerfo, A.; Petrozzi, L.; Petrucci, A.; Mancuso, M.; Siciliano, G. Amyotrophic Lateral Sclerosis and Oxidative Stress: A Double-Blind Therapeutic Trial After Curcumin Supplementation. CNS Neurol. Disord. Drug Targets; 2018; 17, pp. 767-779. [DOI: https://dx.doi.org/10.2174/1871527317666180720162029] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/30033879]

220. Siciliano, G.; Simoncini, C.; Schirinzi, E.; Ricci, G.; Chico, L.; Govoni, A. Amyotrophic lateral sclerosis and Curcumin: A double-blind, placebo-controlled clinical trial. Eur. J. Neurol.; 2020; 27, 874.

221. Dolati, S.; Aghebati-Maleki, L.; Ahmadi, M.; Marofi, F.; Babaloo, Z.; Ayramloo, H.; Jafarisavari, Z.; Oskouei, H.; Afkham, A.; Younesi, V. et al. Nanocurcumin restores aberrant miRNA expression profile in multiple sclerosis, randomized, double-blind, placebo-controlled trial. J. Cell. Physiol.; 2018; 233, pp. 5222-5230. [DOI: https://dx.doi.org/10.1002/jcp.26301]

222. Dolati, S.; Ahmadi, M.; Aghebti-Maleki, L.; Nikmaram, A.; Marofi, F.; Rikhtegar, R.; Ayromlou, H.; Yousefi, M. Nanocurcumin is a potential novel therapy for multiple sclerosis by influencing inflammatory mediators. Pharmacol. Rep.; 2018; 70, pp. 1158-1167. [DOI: https://dx.doi.org/10.1016/j.pharep.2018.05.008]

223. Dolati, S.; Babaloo, Z.; Ayromlou, H.; Ahmadi, M.; Rikhtegar, R.; Rostamzadeh, D.; Roshangar, L.; Nouri, M.; Mehdizadeh, A.; Younesi, V. et al. Nanocurcumin improves regulatory T-cell frequency and function in patients with multiple sclerosis. J. Neuroimmunol.; 2019; 327, pp. 15-21. [DOI: https://dx.doi.org/10.1016/j.jneuroim.2019.01.007] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/30683426]

224. Esposito, T.; Schettino, C.; Polverino, P.; Allocca, S.; Adelfi, L.; D’Amico, A.; Capaldo, G.; Varriale, B.; Di Salle, A.; Peluso, G. et al. Synergistic interplay between curcumin and polyphenol-rich foods in the mediterranean diet: Therapeutic prospects for neurofibromatosis 1 patients. Nutrients; 2017; 9, 783. [DOI: https://dx.doi.org/10.3390/nu9070783] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/28754004]

225. Shadnoush, M.; Zahedi, H.; Norouzy, A.; Sahebkar, A.; Sadeghi, O.; Najafi, A.; Hosseini, S.; Qorbani, M.; Ahmadi, A.; Ardehali, S.H. et al. Effects of supplementation with curcuminoids on serum adipokines in critically ill patients: A randomized double-blind placebo-controlled trial. Phytother. Res.; 2020; 34, pp. 3180-3188. [DOI: https://dx.doi.org/10.1002/ptr.6749] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/32542818]

226. Asadi, S.; Gholami, M.S.; Siassi, F.; Qorbani, M.; Sotoudeh, G. Beneficial effects of nano-curcumin supplement on depression and anxiety in diabetic patients with peripheral neuropathy: A randomized, double-blind, placebo-controlled clinical trial. Phytother. Res.; 2020; 34, pp. 896-903. [DOI: https://dx.doi.org/10.1002/ptr.6571]

227. Bergman, J.; Miodownik, C.; Bersudsky, Y.; Sokolik, S.; Lerner, P.P.; Kreinin, A.; Polakiewicz, J.; Lerner, V. Curcumin as an add-on to antidepressive treatment: A randomized, double-blind, placebo-controlled, pilot clinical study. Clin. Neuropharmacol.; 2013; 36, pp. 73-77. [DOI: https://dx.doi.org/10.1097/WNF.0b013e31828ef969]

228. Decker, C. Curcumin Comparable to Fluoxetine for Treatment of Major Depressive Disorder. Intern. Med. Alert; 2014; 17, 23.

229. Esmaily, H.; Sahebkar, A.; Iranshahi, M.; Ganjali, S.; Mohammadi, A.; Ferns, G.; Ghayour-Mobarhan, M. An investigation of the effects of curcumin on anxiety and depression in obese individuals: A randomized controlled trial. Chin. J. Integr. Med.; 2015; 21, pp. 332-338. [DOI: https://dx.doi.org/10.1007/s11655-015-2160-z]

230. Kanchanatawan, B.; Tangwongchai, S.; Sughondhabhirom, A.; Suppapitiporn, S.; Hemrunrojn, S.; Carvalho, A.F.; Maes, M. Add-on Treatment with Curcumin Has Antidepressive Effects in Thai Patients with Major Depression: Results of a Randomized Double-Blind Placebo-Controlled Study. Neurotox. Res.; 2018; 33, pp. 621-633. [DOI: https://dx.doi.org/10.1007/s12640-017-9860-4]

231. Kawasaki, K.; Muroyama, K.; Murosaki, S. Effect of a water extract of Curcuma longa on emotional states in healthy participants. Bmfh; 2018; 37, pp. 25-29. [DOI: https://dx.doi.org/10.12938/bmfh.17-020]

232. Kuszewski, J.C.; Howe, P.R.C.; Wong, R.H.X. An Exploratory Analysis of Changes in Mental Wellbeing Following Curcumin and Fish Oil Supplementation in Middle-Aged and Older Adults. Nutrients; 2020; 12, 2902. [DOI: https://dx.doi.org/10.3390/nu12102902]

233. Lopresti, A.L.; Drummond, P.D. Efficacy of curcumin, and a saffron/curcumin combination for the treatment of major depression: A randomised, double-blind, placebo-controlled study. J. Affect. Disord.; 2017; 207, pp. 188-196. [DOI: https://dx.doi.org/10.1016/j.jad.2016.09.047] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/27723543]

234. Lopresti, A.L.; Maes, M.; Maker, G.L.; Hood, S.D.; Drummond, P.D. Curcumin for the treatment of major depression: A randomised, double-blind, placebo controlled study. J. Affect. Disord.; 2014; 167, pp. 368-375. [DOI: https://dx.doi.org/10.1016/j.jad.2014.06.001] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/25046624]

235. Lopresti, A.L.; Maes, M.; Meddens, M.J.; Maker, G.L.; Arnoldussen, E.; Drummond, P.D. Curcumin and major depression: A randomised, double-blind, placebo-controlled trial investigating the potential of peripheral biomarkers to predict treatment response and antidepressant mechanisms of change. Eur. Neuropsychopharmacol.; 2015; 25, pp. 38-50. [DOI: https://dx.doi.org/10.1016/j.euroneuro.2014.11.015] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/25523883]

236. Panahi, Y.; Badeli, R.; Karami, G.R.; Sahebkar, A. Investigation of the efficacy of adjunctive therapy with bioavailability-boosted curcuminoids in major depressive disorder. Phytother. Res.; 2015; 29, pp. 17-21. [DOI: https://dx.doi.org/10.1002/ptr.5211] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/25091591]

237. Sanmukhani, J.; Satodia, V.; Trivedi, J.; Patel, T.; Tiwari, D.; Panchal, B.; Goel, A.; Tripathi, C.B. Efficacy and safety of curcumin in major depressive disorder: A randomized controlled trial. Phytother. Res.; 2014; 28, pp. 579-585. [DOI: https://dx.doi.org/10.1002/ptr.5025] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/23832433]

238. Yu, J.J.; Pei, L.B.; Zhang, Y.; Wen, Z.Y.; Yang, J.L. Chronic Supplementation of Curcumin Enhances the Efficacy of Antidepressants in Major Depressive Disorder: A Randomized, Double-Blind, Placebo-Controlled Pilot Study. J. Clin. Psychopharmacol.; 2015; 35, pp. 406-410. [DOI: https://dx.doi.org/10.1097/JCP.0000000000000352]

239. Cox, K.H.; Pipingas, A.; Scholey, A.B. Investigation of the effects of solid lipid curcumin on cognition and mood in a healthy older population. J. Psychopharmacol.; 2015; 29, pp. 642-651. [DOI: https://dx.doi.org/10.1177/0269881114552744]

240. Cox, K.H.M.; White, D.J.; Pipingas, A.; Poorun, K.; Scholey, A. Further Evidence of Benefits to Mood and Working Memory from Lipidated Curcumin in Healthy Older People: A 12-Week, Double-Blind, Placebo-Controlled, Partial Replication Study. Nutrients; 2020; 12, 1678. [DOI: https://dx.doi.org/10.3390/nu12061678]

241. Kuszewski, J.C.; Howe, P.R.C.; Wong, R.H.X. Evaluation of Cognitive Performance following Fish-Oil and Curcumin Supplementation in Middle-Aged and Older Adults with Overweight or Obesity. J. Nutr.; 2020; 150, pp. 3190-3199. [DOI: https://dx.doi.org/10.1093/jn/nxaa299]

242. Rainey-Smith, S.R.; Brown, B.M.; Sohrabi, H.R.; Shah, T.; Goozee, K.G.; Gupta, V.B.; Martins, R.N. Curcumin and cognition: A randomised, placebo-controlled, double-blind study of community-dwelling older adults. Br. J. Nutr.; 2016; 115, pp. 2106-2113. [DOI: https://dx.doi.org/10.1017/S0007114516001203]

243. Ross, S.M. Curcuma longa (Theracumin): A Bioavailable Form of Curcumin and Its Cognitive Benefits. Holist. Nurs. Pract.; 2018; 32, pp. 217-220. [DOI: https://dx.doi.org/10.1097/HNP.0000000000000281] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/29894377]

244. Santos-Parker, J.R.; Lubieniecki, K.L.; Rossman, M.J.; Van Ark, H.J.; Bassett, C.J.; Strahler, T.R.; Chonchol, M.B.; Justice, J.N.; Seals, D.R. Curcumin supplementation and motor-cognitive function in healthy middle-aged and older adults. Nutr. Healthy Aging; 2018; 4, pp. 323-333. [DOI: https://dx.doi.org/10.3233/NHA-170029]

245. Seen, W.P.; Mun, T.Y.; Mohanty, B.K.; Ebenezer, E.; Sugathan, S. Curcumin consumption and cognitive function in elderly. Int. J. Pharm. Sci. Res.; 2017; 8, pp. 5367-5372. [DOI: https://dx.doi.org/10.13040/IJPSR.0975-8232.8(12).5367-72]

246. Small, G.W.; Siddarth, P.; Li, Z.; Miller, K.J.; Ercoli, L.; Emerson, N.D.; Martinez, J.; Wong, K.P.; Liu, J.; Merrill, D.A. et al. Memory and Brain Amyloid and Tau Effects of a Bioavailable Form of Curcumin in Non-Demented Adults: A Double-Blind, Placebo-Controlled 18-Month Trial. Am. J. Geriatr. Psychiatry; 2018; 26, pp. 266-277. [DOI: https://dx.doi.org/10.1016/j.jagp.2017.10.010] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/29246725]

247. Baum, L.; Lam, C.W.; Cheung, S.K.; Kwok, T.; Lui, V.; Tsoh, J.; Lam, L.; Leung, V.; Hui, E.; Ng, C. et al. Six-month randomized, placebo-controlled, double-blind, pilot clinical trial of curcumin in patients with Alzheimer disease. J. Clin. Psychopharmacol.; 2008; 28, pp. 110-113. [DOI: https://dx.doi.org/10.1097/jcp.0b013e318160862c]

248. Ringman, J.M.; Frautschy, S.A.; Teng, E.; Begum, A.N.; Bardens, J.; Beigi, M.; Gylys, K.H.; Badmaev, V.; Heath, D.D.; Apostolova, L.G. et al. Oral curcumin for Alzheimer’s disease: Tolerability and efficacy in a 24-week randomized, double blind, placebo-controlled study. Alzheimer Res. Ther.; 2012; 4, 43. [DOI: https://dx.doi.org/10.1186/alzrt146]

249. Abbas, S.H.; Abdulridha, M.K.; Najeb, A.A. Potential benefit of curcumin adjuvant therapy to the standard Helicobacter pylori eradication therapy in patients with peptic ulcer disease. Asian J. Pharm. Clin. Res.; 2017; 10, pp. 313-317. [DOI: https://dx.doi.org/10.22159/ajpcr.2017.v10i5.17462]

250. Judaki, A.; Rahmani, A.; Feizi, J.; Asadollahi, K.; Hafezi Ahmadi, M.R. Curcumin in Combination with Triple Therapy Regimes Ameliorates Oxidative Stress and Histopathologic Changes in Chronic Gastritis-Associated Helicobacter Pylori Infection. Arq. De Gastroenterol.; 2017; 54, pp. 177-182. [DOI: https://dx.doi.org/10.1590/s0004-2803.201700000-18]

251. Khonche, A.; Biglarian, O.; Panahi, Y.; Valizadegan, G.; Soflaei, S.S.; Ghamarchehreh, M.E.; Majeed, M.; Sahebkar, A. Adjunctive Therapy with Curcumin for Peptic Ulcer: A Randomized Controlled Trial. Drug Res.; 2016; 66, pp. 444-448. [DOI: https://dx.doi.org/10.1055/s-0042-109394]

252. Koosirirat, C.; Linpisarn, S.; Changsom, D.; Chawansuntati, K.; Wipasa, J. Investigation of the anti-inflammatory effect of Curcuma longa in Helicobacter pylori-infected patients. Int. Immunopharmacol.; 2010; 10, pp. 815-818. [DOI: https://dx.doi.org/10.1016/j.intimp.2010.04.021] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/20438867]

253. Kositchaiwat, C.; Kositchaiwat, S.; Havanondha, J. Curcuma longa Linn. in the treatment of gastric ulcer comparison to liquid antacid: A controlled clinical trial. J. Med. Assoc. Thail.; 1993; 76, pp. 601-605.

254. Patcharatrakul, T.; Vutrapongwatana, U.; Phromchampa, W.; Chaiwatanarat, T.; Werawatganon, D.; Gonlachanvit, S. Effects of 4-week curcuminoids on clinical and gastric functions in patients with overlapping gastroesophageal reflux disease (GERD) and functional dyspepsia (FD): A randomized control study. Gastroenterology; 2020; 158, S1148. [DOI: https://dx.doi.org/10.1016/S0016-5085(20)33546-0]

255. Patcharatrakul, T.; Vutrapongwatana, U.; Phromchampa, W.; Chaiwatanarat, T.; Werawatganon, D.; Gonlachanvit, S. Acute effect of curcuminoid on esophageal and gastric physiology: A randomized corss-over trial in gastroesophageal reflux disease (GERD) patients with positive pH monitoring. Gastroenterology; 2020; 158, pp. S1075-S1076. [DOI: https://dx.doi.org/10.1016/S0016-5085(20)33369-2]

256. Prucksunand, C.; Indrasukhsri, B.; Leethochawalit, M.; Hungspreugs, K. Phase II clinical trial on effect of the long turmeric (Curcuma longa Linn) on healing of peptic ulcer. Southeast Asian J. Trop. Med. Public Health; 2001; 32, pp. 208-215.

257. Puttapitakpong, C.; Jearjesdakul, J. Effectiveness of curcuma longa linn compared with omeprazole on treatment of functional dyspepsia. Gastroenterology; 2016; 150, S43. [DOI: https://dx.doi.org/10.1016/S0016-5085(16)30271-2]

258. Rawat, N.; McAdam, E.; Alhamdani, A.; Cronin, J.G.; Lewis, P.D.; Griffiths, P.; Manson, J.M.; Caplin, S.; Brown, T.H.; Baxter, J. et al. Oral curcumin suppresses NF-κB activity in Barrett’s esophagus: A pilot study. Gastroenterology; 2009; 136, A297. [DOI: https://dx.doi.org/10.1016/S0016-5085(09)61354-8]

259. Szymanski, M.C.; Gillum, T.L.; Gould, L.M.; Morin, D.S.; Kuennen, M.R. Short-term dietary curcumin supplementation reduces gastrointestinal barrier damage and physiological strain responses during exertional heat stress. J. Appl. Physiol.; 2018; 124, pp. 330-340. [DOI: https://dx.doi.org/10.1152/japplphysiol.00515.2017]

260. Van Dau, N.; Ham, N.N.; Khac, D.H.; Lam, N.T.; Son, P.T.; Tan, N.T.; Van, D.D.; Dahlgren, S.; Grabe, M.; Johansson, R. et al. The effects of a traditional drug, turmeric (Curcuma longa), and placebo on the healing of duodenal ulcer. Phytomedicine; 1998; 5, pp. 29-34. [DOI: https://dx.doi.org/10.1016/S0944-7113(98)80056-1]

261. Yongwatana, K.; Harinwan, K.; Chirapongsathorn, S.; Opuchar, K.; Sanpajit, T.; Piyanirun, W.; Puttapitakpong, C. Curcuma long Linn versus omeprazole in treatment of functonal dyspepsia, a randomized, double-blind, pacebo-controlled trial. Gastroenterology; 2019; 156, S171. [DOI: https://dx.doi.org/10.1016/S0016-5085(19)37219-1]

262. Bommelaer, G.; Laharie, D.; Nancey, S.; Hebuterne, X.; Roblin, X.; Nachury, M.; Peyrin-Biroulet, L.; Fumery, M.; Richard, D.; Pereira, B. et al. Oral Curcumin No More Effective Than Placebo in Preventing Recurrence of Crohn’s Disease After Surgery in a Randomized Controlled Trial. Clin. Gastroenterol. Hepatol.; 2020; 18, pp. 1553-1560. [DOI: https://dx.doi.org/10.1016/j.cgh.2019.08.041] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31470175]

263. Sugimoto, K.; Ikeya, K.; Bamba, S.; Andoh, A.; Yamasaki, H.; Mitsuyama, K.; Nasuno, M.; Tanaka, H.; Matsuura, A.; Kato, M. et al. Highly bioavailable curcumin derivative ameliorates Crohn’s disease symptoms: A randomized, double-blind, multicenter study. J. Crohn Colitis; 2020; 15, 15. [DOI: https://dx.doi.org/10.1093/ecco-jcc/jjaa097] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/32412598]

264. Pitisuttithum, P.; Patcharatrakul, T.; Werawatganon, D.; Gonlachanvit, S. A randomized controlled study on the effects of curcuminoid on instestinal permeability evaluated by urine lactulose mannitol ratio (LNR) after aspirin ingestion. Gastroenterology; 2019; 156, S504. [DOI: https://dx.doi.org/10.1016/S0016-5085(19)38136-3]

265. Tuntipopipat, S.; Judprasong, K.; Zeder, C.; Wasantwisut, E.; Winichagoon, P.; Charoenkiatkul, S.; Hurrell, R.; Walczyk, T. Chili, but not turmeric, inhibits iron absorption in young women from an iron-fortified composite meal. J. Nutr.; 2006; 136, pp. 2970-2974. [DOI: https://dx.doi.org/10.1093/jn/136.12.2970] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/17116705]

266. Bundy, R.; Walker, A.F.; Middleton, R.W.; Booth, J. Turmeric extract may improve irritable bowel syndrome symptomology in otherwise healthy adults: A pilot study. J. Altern. Complement. Med.; 2004; 10, pp. 1015-1018. [DOI: https://dx.doi.org/10.1089/acm.2004.10.1015] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/15673996]

267. Peterson, C.T.; Vaughn, A.R.; Sharma, V.; Chopra, D.; Mills, P.J.; Peterson, S.N.; Sivamani, R.K. Effects of Turmeric and Curcumin Dietary Supplementation on Human Gut Microbiota: A Double-Blind, Randomized, Placebo-Controlled Pilot Study. J. Evid. Based Integr. Med.; 2018; 23, 2515690X18790725. [DOI: https://dx.doi.org/10.1177/2515690X18790725] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/30088420]

268. Atkinson, R.J.; Hunter, J.O. A double blind, placebo controlled randomised trial of Curcuma extract in the treatment of steroid dependent inflammatory bowel disease. Gastroenterology; 2003; 124, A205. [DOI: https://dx.doi.org/10.1016/S0016-5085(03)81031-4]

269. Banerjee, R.; Pal, P.; Penmetsa, A.; Kathi, P.; Girish, G.; Goren, I.; Reddy, D.N. Novel Bioenhanced Curcumin With Mesalamine for Induction of Clinical and Endoscopic Remission in Mild-to-Moderate Ulcerative Colitis: A Randomized Double-Blind Placebo-controlled Pilot Study. J. Clin. Gastroenterol.; 2020; 55, pp. 702-708. [DOI: https://dx.doi.org/10.1097/MCG.0000000000001416]

270. Hanai, H.; Iida, T.; Takeuchi, K.; Watanabe, F.; Maruyama, Y.; Andoh, A.; Tsujikawa, T.; Fujiyama, Y.; Mitsuyama, K.; Sata, M. et al. Curcumin maintenance therapy for ulcerative colitis: Randomized, multicenter, double-blind, placebo-controlled trial. Clin. Gastroenterol. Hepatol.; 2006; 4, pp. 1502-1506. [DOI: https://dx.doi.org/10.1016/j.cgh.2006.08.008]

271. Kedia, S.; Bhatia, V.; Thareja, S.; Garg, S.; Mouli, V.P.; Bopanna, S.; Tiwari, V.; Makharia, G.; Ahuja, V. Low dose oral curcumin is not effective in induction of remission in mild to moderate ulcerative colitis: Results from a randomized double blind placebo controlled trial. World J. Gastrointest. Pharmacol. Ther.; 2017; 8, pp. 147-154. [DOI: https://dx.doi.org/10.4292/wjgpt.v8.i2.147]

272. Kumar, S.; Dutta, U.; Shah, J.; Singh, P.; Vaishnavi, C.; Prasad, K.K.; Singh, K. Impact of curcuma longa on clinical activity and inflammatory markers in patients with active ulcerative colitis: A double-blind randomised placebo-controlled trial. J. Crohns Colitis; 2019; 13, pp. S322-S323. [DOI: https://dx.doi.org/10.1093/ecco-jcc/jjy222.551]

273. Masoodi, M.; Mahdiabadi, M.A.; Mokhtare, M.; Agah, S.; Kashani, A.H.F.; Rezadoost, A.M.; Sabzikarian, M.; Talebi, A.; Sahebkar, A. The efficacy of curcuminoids in improvement of ulcerative colitis symptoms and patients’ self-reported well-being: A randomized double-blind controlled trial. J. Cell. Biochem.; 2018; 119, pp. 9552-9559. [DOI: https://dx.doi.org/10.1002/jcb.27273] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/30132960]

274. Sadeghi, N.; Mansoori, A.; Shayesteh, A.; Hashemi, S.J. The effect of curcumin supplementation on clinical outcomes and inflammatory markers in patients with ulcerative colitis. Phytother. Res.; 2020; 34, pp. 1123-1133. [DOI: https://dx.doi.org/10.1002/ptr.6581] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31802559]

275. Salomon, N.; Lang, A.; Kopylov, U.; Lahat, A.; Har-Noy, O.; Wu, J.; Ching, J.; Cheong, P.K.; Avidan, B.; Gamus, D. et al. Curcumin Add-on Therapy for Remission Induction in Mild-moderate Active Ulcerative Colitis: A Multi-center, Randomized, Placebo-Controlled Trial. Clin. Gastroenterol. Hepatol.; 2015; 13, pp. 1381-1382. [DOI: https://dx.doi.org/10.1016/j.cgh.2015.04.032]

276. Agarwal, K.A.; Tripathi, C.D.; Agarwal, B.B.; Saluja, S. Efficacy of turmeric (curcumin) in pain and postoperative fatigue after laparoscopic cholecystectomy: A double-blind, randomized placebo-controlled study. Surg. Endosc.; 2011; 25, pp. 3805-3810. [DOI: https://dx.doi.org/10.1007/s00464-011-1793-z] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/21671126]

277. Eaton, J.E.; Nelson, K.M.; Gossard, A.A.; Carey, E.J.; Tabibian, J.H.; Lindor, K.D.; LaRusso, N.F. Efficacy and safety of curcumin in primary sclerosing cholangitis: An open label pilot study. Scand. J. Gastroenterol.; 2019; 54, pp. 633-639. [DOI: https://dx.doi.org/10.1080/00365521.2019.1611917]

278. Ghaffarzadegan, T.; Zanzer, Y.C.; Ostman, E.; Hallenius, F.; Essen, S.; Sandahl, M.; Nyman, M. Postprandial Responses of Serum Bile Acids in Healthy Humans after Ingestion of Turmeric before Medium/High-Fat Breakfasts. Mol. Nutr. Food Res.; 2019; 63, e1900672. [DOI: https://dx.doi.org/10.1002/mnfr.201900672] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31411373]

279. Rasyid, A.; Lelo, A. The effect of curcumin and placebo on human gall-bladder function: An ultrasound study. Aliment. Pharmacol. Ther.; 1999; 13, pp. 245-249. [DOI: https://dx.doi.org/10.1046/j.1365-2036.1999.00464.x]

280. Rasyid, A.; Rahman, A.R.; Jaalam, K.; Lelo, A. The chronopharmacological effect of curcumin on human gall-bladder. Med. J. Indones.; 2001; 10, pp. 219-223. [DOI: https://dx.doi.org/10.13181/mji.v10i4.40]

281. Rasyid, A.; Rahman, A.R.; Jaalam, K.; Lelo, A. Effect of different curcumin dosages on human gall bladder. Asia Pac. J. Clin. Nutr.; 2002; 11, pp. 314-318. [DOI: https://dx.doi.org/10.1046/j.1440-6047.2002.00296.x]

282. Abd El-Ghany, M.A.; Emad, A.S.; Amani, M.I. Nutraceutical effects of some Egyptian herbs on liver failure patients. World J. Med. Sci.; 2014; 10, pp. 1-11. [DOI: https://dx.doi.org/10.5829/idosi.wjms.2014.10.1.1136]

283. Kertia, N.; Asdie, A.H.; Rochmah, W. Marsetyawan. Comparison of the effects of curcuminoid from Curcuma domestica Val. rhizome extract and diclofenac sodium on the liver function of patients with osteoarthritis. J. Pharmacogn. Phytother.; 2012; 4, pp. 62-65. [DOI: https://dx.doi.org/10.5897/JPP11.079]

284. Kim, S.W.; Ha, K.C.; Choi, E.K.; Jung, S.Y.; Kim, M.G.; Kwon, D.Y.; Yang, H.J.; Kim, M.J.; Kang, H.J.; Back, H.I. et al. The effectiveness of fermented turmeric powder in subjects with elevated alanine transaminase levels: A randomised controlled study. BMC Complement. Altern. Med.; 2013; 13, 58. [DOI: https://dx.doi.org/10.1186/1472-6882-13-58] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/23497020]

285. N, T.K.; Thomas, J.V.; Nair, S.S.; J, N.M.; Maliakel, B.P.; Krishnakumar, I.M. A Novel Curcumin-Galactomannoside Complex Delivery System Improves Hepatic Function Markers in Chronic Alcoholics: A Double-Blinded, randomized, Placebo-Controlled Study. BioMed Res. Int.; 2018; 2018, 9159281. [DOI: https://dx.doi.org/10.1155/2018/9159281]

286. Nouri-Vaskeh, M.; Afshan, H.; Malek Mahdavi, A.; Alizadeh, L.; Fan, X.; Zarei, M. Curcumin ameliorates health-related quality of life in patients with liver cirrhosis: A randomized, double-blind placebo-controlled trial. Complement. Ther. Med.; 2020; 49, 102351. [DOI: https://dx.doi.org/10.1016/j.ctim.2020.102351] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/32147077]

287. Nouri-Vaskeh, M.; Malek Mahdavi, A.; Afshan, H.; Alizadeh, L.; Zarei, M. Effect of curcumin supplementation on disease severity in patients with liver cirrhosis: A randomized controlled trial. Phytother. Res.; 2020; 34, pp. 1446-1454. [DOI: https://dx.doi.org/10.1002/ptr.6620] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/32017253]

288. Choi, Y.H.; Han, D.H.; Kim, S.W.; Kim, M.J.; Sung, H.H.; Jeon, H.G.; Jeong, B.C.; Seo, S.I.; Jeon, S.S.; Lee, H.M. et al. A randomized, double-blind, placebo-controlled trial to evaluate the role of curcumin in prostate cancer patients with intermittent androgen deprivation. Prostate; 2019; 79, pp. 614-621. [DOI: https://dx.doi.org/10.1002/pros.23766]

289. Hejazi, J.; Rastmanesh, R.; Taleban, F.A.; Molana, S.H.; Ehtejab, G. A pilot clinical trial of radioprotective effects of curcumin supplementation in patients with prostate cancer. J. Cancer Sci. Ther.; 2013; 5, pp. 320-324. [DOI: https://dx.doi.org/10.4172/1948-5956.1000222]

290. Hejazi, J.; Rastmanesh, R.; Taleban, F.A.; Molana, S.H.; Hejazi, E.; Ehtejab, G.; Hara, N. Effect of Curcumin Supplementation During Radiotherapy on Oxidative Status of Patients with Prostate Cancer: A Double Blinded, Randomized, Placebo-Controlled Study. Nutr. Cancer; 2016; 68, pp. 77-85. [DOI: https://dx.doi.org/10.1080/01635581.2016.1115527]

291. Ledda, A.; Belcaro, G.; Dugall, M.; Luzzi, R.; Scoccianti, M.; Togni, S.; Appendino, G.; Ciammaichella, G. Meriva, a lecithinized curcumin delivery system, in the control of benign prostatic hyperplasia: A pilot, product evaluation registry study. Panminerva Med.; 2012; 54, pp. 17-22.

292. Saadipoor, A.; Razzaghdoust, A.; Simforoosh, N.; Mahdavi, A.; Bakhshandeh, M.; Moghadam, M.; Abdollahi, H.; Mofid, B. Randomized, double-blind, placebo-controlled phase II trial of nanocurcumin in prostate cancer patients undergoing radiotherapy. Phytother. Res.; 2019; 33, pp. 370-378. [DOI: https://dx.doi.org/10.1002/ptr.6230]

293. Garg, M.; Chintamani,; Tandon, M.; Bamal, R. To study the role of curcumin in LABC patients undergoing NACT. Indian J. Surg. Oncol.; 2013; 4, pp. 174-175. [DOI: https://dx.doi.org/10.1007/s13193-013-0219-x]

294. Kalluru, H.; Kondaveeti, S.S.; Telapolu, S.; Kalachaveedu, M. Turmeric supplementation improves the quality of life and hematological parameters in breast cancer patients on paclitaxel chemotherapy: A case series. Complement. Ther. Clin. Pract.; 2020; 41, 101247. [DOI: https://dx.doi.org/10.1016/j.ctcp.2020.101247] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/33099272]

295. Nct. Phase II Study of Curcumin vs. Placebo for Chemotherapy-Treated Breast Cancer Patients Undergoing Radiotherapy. 2012; Available online: https://clinicaltrials.gov/show/nct01740323 (accessed on 20 February 2023).

296. Ryan, J.L.; Heckler, C.E.; Ling, M.; Katz, A.; Williams, J.P.; Pentland, A.P.; Morrow, G.R. Curcumin for radiation dermatitis: A randomized, double-blind, placebo-controlled clinical trial of thirty breast cancer patients. Radiat. Res.; 2013; 180, pp. 34-43. [DOI: https://dx.doi.org/10.1667/RR3255.1] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/23745991]

297. Ryan Wolf, J.; Heckler, C.E.; Guido, J.J.; Peoples, A.R.; Gewandter, J.S.; Ling, M.; Vinciguerra, V.P.; Anderson, T.; Evans, L.; Wade, J. et al. Oral curcumin for radiation dermatitis: A URCC NCORP study of 686 breast cancer patients. Support Care Cancer; 2018; 26, pp. 1543-1552. [DOI: https://dx.doi.org/10.1007/s00520-017-3957-4]

298. Carroll, R.E.; Benya, R.V.; Turgeon, D.K.; Vareed, S.; Neuman, M.; Rodriguez, L.; Kakarala, M.; Carpenter, P.M.; McLaren, C.; Meyskens, F.L., Jr. et al. Phase IIa clinical trial of curcumin for the prevention of colorectal neoplasia. Cancer Prev. Res.; 2011; 4, pp. 354-364. [DOI: https://dx.doi.org/10.1158/1940-6207.CAPR-10-0098] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/21372035]

299. Cruz-Correa, M.; Hylind, L.M.; Marrero, J.H.; Zahurak, M.L.; Murray-Stewart, T.; Casero, R.A., Jr.; Montgomery, E.A.; Iacobuzio-Donahue, C.; Brosens, L.A.; Offerhaus, G.J. et al. Efficacy and Safety of Curcumin in Treatment of Intestinal Adenomas in Patients With Familial Adenomatous Polyposis. Gastroenterology; 2018; 155, pp. 668-673. [DOI: https://dx.doi.org/10.1053/j.gastro.2018.05.031]

300. Gunther, J.R.; Chadha, A.S.; Yang, P.Y.; Munsell, M.F.; Das, P.; Delclos, M.E.; Foo, W.C.; Kaur, H.; Clemons, M.; Mathew, G.G. et al. A Phase 2 Randomized Double Blinded Study Evaluating the Efficacy of Curcumin With Pre-Operative Chemoradiation for Rectal Cancer. Int. J. Radiat. Oncol. Biol. Phys.; 2017; 98, E7. [DOI: https://dx.doi.org/10.1016/j.ijrobp.2017.02.057]

301. Howells, L.M.; Iwuji, C.O.O.; Irving, G.R.B.; Barber, S.; Walter, H.; Sidat, Z.; Griffin-Teall, N.; Singh, R.; Foreman, N.; Patel, S.R. et al. Curcumin Combined with FOLFOX Chemotherapy Is Safe and Tolerable in Patients with Metastatic Colorectal Cancer in a Randomized Phase IIa Trial. J. Nutr.; 2019; 149, pp. 1133-1139. [DOI: https://dx.doi.org/10.1093/jn/nxz029]

302. Santosa, D.; Suharti, C.; Riwanto, I.; Dharmana, E.; Pangarsa, E.A.; Setiawan, B.; Suyono, S.; Lumban, T.M. The effects of curcumin addition on remission status of multiple myeloma patients. Hemasphere; 2019; 3, 975. [DOI: https://dx.doi.org/10.1097/01.HS9.0000567168.14031.ac]

303. Golombick, T.; Diamond, T.H.; Badmaev, V.; Manoharan, A.; Ramakrishna, R. The potential role of curcumin in patients with monoclonal gammopathy of undefined significance--its effect on paraproteinemia and the urinary N-telopeptide of type I collagen bone turnover marker. Clin. Cancer Res.; 2009; 15, pp. 5917-5922. [DOI: https://dx.doi.org/10.1158/1078-0432.CCR-08-2217]

304. Golombick, T.; Diamond, T.H.; Manoharan, A.; Ramakrishna, R. Monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, and curcumin: A randomized, double-blind placebo-controlled cross-over 4g study and an open-label 8g extension study. Am. J. Hematol.; 2012; 87, pp. 455-460. [DOI: https://dx.doi.org/10.1002/ajh.23159] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/22473809]

305. Nct. Curcumin (Diferuloylmethane Derivative) With or Without Bioperine in Patients With Multiple Myeloma. 2005; Available online: https://clinicaltrials.gov/show/nct00113841 (accessed on 20 February 2023).

306. Arun, P.; Sagayaraj, A.; Azeem Mohiyuddin, S.M.; Santosh, D. Role of turmeric extract in minimising mucositis in patients receiving radiotherapy for head and neck squamous cell cancer: A randomised, placebo-controlled trial. J. Laryngol. Otol.; 2020; 134, pp. 159-164. [DOI: https://dx.doi.org/10.1017/S0022215120000316] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/32029014]

307. Delavarian, Z.; Pakfetrat, A.; Ghazi, A.; Jaafari, M.R.; Homaei Shandiz, F.; Dalirsani, Z.; Mohammadpour, A.H.; Rahimi, H.R. Oral administration of nanomicelle curcumin in the prevention of radiotherapy-induced mucositis in head and neck cancers. Spec. Care Dent.; 2019; 39, pp. 166-172. [DOI: https://dx.doi.org/10.1111/scd.12358]

308. Neetha, M.C.; Panchaksharappa, M.G.; Pattabhiramasastry, S.; Shivaprasad, N.V.; Venkatesh, U.G. Chemopreventive Synergism between Green Tea Extract and Curcumin in Patients with Potentially Malignant Oral Disorders: A Double-blind, Randomized Preliminary Study. J. Contemp. Dent. Pract.; 2020; 21, pp. 521-531. [DOI: https://dx.doi.org/10.5005/jp-journals-10024-2823] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/32690834]

309. Joshi, J.V.; Paradkar, P.H.; Jagtap, S.S.; Agashe, S.V.; Soman, G.; Vaidya, A.B. Chemopreventive potential and safety profile of a Curcuma longa extract in women with cervical low-grade squamous intraepithelial neoplasia. Asian Pac. J. Cancer Prev.; 2011; 12, pp. 3305-3311.

310. Purbadi, S.; Rustamadji, P.; Prijanti, A.R.; Sekarutami, S.M.; Sutrisna, B.; Suyatna, F.D.; Andrijono, A. Biocurcumin as Radiosensitiser for Cervical Cancer Study (BRACES): A Double-Blind Randomised Placebo-Controlled Trial. Evid. Based Complement. Altern. Med.; 2020; 2020, 10. [DOI: https://dx.doi.org/10.1155/2020/1986793]

311. Tuyaerts, S.; Rombauts, K.; Everaert, T.; Van Nuffel, A.M.T.; Amant, F. A Phase 2 Study to Assess the Immunomodulatory Capacity of a Lecithin-based Delivery System of Curcumin in Endometrial Cancer. Front. Nutr.; 2018; 5, 138. [DOI: https://dx.doi.org/10.3389/fnut.2018.00138]

312. Dhillon, N.; Aggarwal, B.B.; Newman, R.A.; Wolff, R.A.; Kunnumakkara, A.B.; Abbruzzese, J.L.; Ng, C.S.; Badmaev, V.; Kurzrock, R. Phase II trial of curcumin in patients with advanced pancreatic cancer. Clin. Cancer Res.; 2008; 14, pp. 4491-4499. [DOI: https://dx.doi.org/10.1158/1078-0432.CCR-08-0024]

313. Parsons, H.A.; Baracos, V.E.; Hong, D.S.; Abbruzzese, J.; Bruera, E.; Kurzrock, R. The effects of curcumin (diferuloylmethane) on body composition of patients with advanced pancreatic cancer. Oncotarget; 2016; 7, pp. 20293-20304. [DOI: https://dx.doi.org/10.18632/oncotarget.7773]

314. Srivastava, A.K.; Singh, D.; Tewari, M.; Shukla, H.S.; Roy, B.K. Impact of turmeric as dietary approach on HER2 status in blood of gastric cancer patients. Int. J. Phytomedicine; 2014; 6, pp. 293-299.

315. Farhadi, M.; Bakhshandeh, M.; Shafiei, B.; Mahmoudzadeh, A.; Hosseinimehr, S.J. The radioprotective effects of nano-curcumin against genotoxicity induced by iodine-131 in patients with differentiated thyroid carcinoma (DTC) by micronucleus assay. Int. J. Cancer Manag.; 2018; 11, e14193. [DOI: https://dx.doi.org/10.5812/ijcm.61383]

316. Sandoughdaran, S.; Razzaghdoust, A.; Tabibi, A.; Basiri, A.; Simforoosh, N.; Mofid, B. Randomized, Double-blind Pilot Study of Nanocurcumin in Bladder Cancer Patients Receiving Induction Chemotherapy. Urol. J.; 2020; 04, 30. [DOI: https://dx.doi.org/10.22037/uj.v0i0.5719]

317. Belcaro, G.; Hosoi, M.; Pellegrini, L.; Appendino, G.; Ippolito, E.; Ricci, A.; Ledda, A.; Dugall, M.; Cesarone, M.R.; Maione, C. et al. A controlled study of a lecithinized delivery system of curcumin (Meriva^®) to alleviate the adverse effects of cancer treatment. Phytother. Res. PTR; 2014; 28, pp. 444-450. [DOI: https://dx.doi.org/10.1002/ptr.5014] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/23775598]

318. Giovanni, A. Curcumin in cancer supportive care: Hype or hope?. Eur. J. Integr. Med.; 2012; 4, pp. 18-19. [DOI: https://dx.doi.org/10.1016/j.eujim.2012.07.517]

319. Panahi, Y.; Saadat, A.; Beiraghdar, F.; Nouzari, S.M.H.; Jalalian, H.R.; Sahebkar, A. Antioxidant effects of bioavailability-enhanced curcuminoids in patients with solid tumors: A randomized double-blind placebo-controlled trial. J. Funct. Foods; 2014; 6, pp. 615-622. [DOI: https://dx.doi.org/10.1016/j.jff.2013.12.008]

320. Panahi, Y.; Saadat, A.; Beiraghdar, F.; Sahebkar, A. Adjuvant therapy with bioavailability-boosted curcuminoids suppresses systemic inflammation and improves quality of life in patients with solid tumors: A randomized double-blind placebo-controlled trial. Phytother. Res.; 2014; 28, pp. 1461-1467. [DOI: https://dx.doi.org/10.1002/ptr.5149]

321. Prasongsook, N.; Sitalarom, K.; Saichaemchan, S.; Peechatanan, K.; Chaiworramukkul, A. A double-blind, placebo-controlled randomized phase II study: Evaluating the effect of curcumin for treatment of cancer anorexia-cachexia syndrome in solid cancer patients. J. Clin. Oncol.; 2019; 37, 1. [DOI: https://dx.doi.org/10.1200/JCO.2019.37.15_suppl.e23151]

322. Akazawa, N.; Choi, Y.; Miyaki, A.; Tanabe, Y.; Sugawara, J.; Ajisaka, R. Effects of curcumin intake and aerobic exercise training on arterial compliance in postmenopausal women. Artery Res.; 2013; 7, pp. 67-72. [DOI: https://dx.doi.org/10.1016/j.artres.2012.09.003]

323. Aslanabadi, N.; Entezari-Maleki, T.; Rezaee, H.; Jafarzadeh, H.R.; Vahedpour, R. Curcumin for the prevention of myocardial injury following elective percutaneous coronary intervention; a pilot randomized clinical trial. Eur. J. Pharmacol.; 2019; 858, 172471. [DOI: https://dx.doi.org/10.1016/j.ejphar.2019.172471] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31228455]

324. Barber-Chamoux, N.; Milenkovic, D.; Verny, M.A.; Habauzit, V.; Pereira, B.; Lambert, C.; Richard, D.; Boby, C.; Mazur, A.; Lusson, J.R. et al. Substantial variability across individuals in the vascular response and nutrigenomic response to an acute intake of curcumin: A randomised controlled trial. J. Hypertens.; 2018; 36, e97. [DOI: https://dx.doi.org/10.1097/01.hjh.0000539247.51050.28]

325. Campbell, M.S.; Berrones, A.J.; Krishnakumar, I.M.; Charnigo, R.J.; Westgate, P.M.; Fleenor, B.S. Responsiveness to curcumin intervention is associated with reduced aortic stiffness in young, obese men with higher initial stiffness. J. Funct. Foods; 2017; 29, pp. 154-160. [DOI: https://dx.doi.org/10.1016/j.jff.2016.12.013]

326. Choi, Y.; Tanabe, Y.; Akazawa, N.; Zempo-Miyaki, A.; Maeda, S. Curcumin supplementation attenuates the decrease in endothelial function following eccentric exercise. J. Exerc. Nutr. Biochem.; 2019; 23, pp. 7-12. [DOI: https://dx.doi.org/10.20463/jenb.2019.0010]

327. Kuszewski, J.C.; Wong, R.H.X.; Wood, L.G.; Howe, P.R.C. Effects of fish oil and curcumin supplementation on cerebrovascular function in older adults: A randomized controlled trial. Nutr. Metab. Cardiovasc. Dis.; 2020; 30, pp. 625-633. [DOI: https://dx.doi.org/10.1016/j.numecd.2019.12.010] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/32127335]

328. Mohammad Pour, A.H.; Dastani, M.; Salari, R.; Radbin, S.; Mehri, S.; Ghorbani, M.; Karimani, A.; Salari, M. Curcumin effects on myeloperoxidase, interleukin-18 and matrix metalloproteinase-9 inflammatory biomarkers in patients with unstable angina: A randomized clinical trial. Avicenna J.; 2019; 9, pp. 428-435.

329. Oliver, J.M.; Stoner, L.; Rowlands, D.S.; Caldwell, A.R.; Sanders, E.; Kreutzer, A.; Mitchell, J.B.; Purpura, M.; Jager, R. Novel Form of Curcumin Improves Endothelial Function in Young, Healthy Individuals: A Double-Blind Placebo Controlled Study. J. Nutr. Metab.; 2016; 2016, 1089653. [DOI: https://dx.doi.org/10.1155/2016/1089653] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/27630772]

330. Santos-Parker, J.R.; Strahler, T.R.; Bassett, C.J.; Bispham, N.Z.; Chonchol, M.B.; Seals, D.R. Curcumin supplementation improves vascular endothelial function in healthy middle-aged and older adults by increasing nitric oxide bioavailability and reducing oxidative stress. Aging; 2017; 9, pp. 187-208. [DOI: https://dx.doi.org/10.18632/aging.101149] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/28070018]

331. Sugawara, J.; Akazawa, N.; Miyaki, A.; Choi, Y.; Tanabe, Y.; Imai, T.; Maeda, S. Effect of endurance exercise training and curcumin intake on central arterial hemodynamics in postmenopausal women: Pilot study. Am. J. Hypertens.; 2012; 25, pp. 651-656. [DOI: https://dx.doi.org/10.1038/ajh.2012.24]

332. Sukardi, R.; Sastroasmoro, S.; Siregar, N.C.; Djer, M.M.; Suyatna, F.D.; Sadikin, M.; Ibrahim, N.; Rahayuningsih, S.E.; Witarto, A.B. The role of curcumin as an inhibitor of oxidative stress caused by ischaemia re-perfusion injury in tetralogy of Fallot patients undergoing corrective surgery. Cardiol. Young; 2016; 26, pp. 431-438. [DOI: https://dx.doi.org/10.1017/S1047951115000360]

333. Akazawa, N.; Choi, Y.; Miyaki, A.; Tanabe, Y.; Sugawara, J.; Ajisaka, R.; Maeda, S. Curcumin ingestion and exercise training improve vascular endothelial function in postmenopausal women. Nutr. Res.; 2012; 32, pp. 795-799. [DOI: https://dx.doi.org/10.1016/j.nutres.2012.09.002]

334. Alwi, I.; Santoso, T.; Suyono, S.; Sutrisna, B.; Suyatna, F.D.; Kresno, S.B.; Ernie, S. The effect of curcumin on lipid level in patients with acute coronary syndrome. Acta Med.; 2008; 40, pp. 201-210.

335. Dastani, M.; Bigdelu, L.; Hoseinzadeh, M.; Rahimi, H.R.; Karimani, A.; Hooshang Mohammadpour, A.; Salari, M. The effects of curcumin on the prevention of atrial and ventricular arrhythmias and heart failure in patients with unstable angina: A randomized clinical trial. Avicenna J.; 2019; 9, pp. 1-9.

336. Garg, A.X.; Devereaux, P.J.; Hill, A. Oral curcumin in elective abdominal aortic aneurysm repair: A multicentre randomized controlled trial. Can. Med. Assoc. J.; 2018; 190, E1425. [DOI: https://dx.doi.org/10.1503/cmaj.180510] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/30373740]

337. Morimoto, T.; Wada, H.; Sunagawa, Y.; Fujita, M.; Kakeya, H.; Imaizumi, A.; Hashimoto, T.; Akao, M.; Katanasaka, Y.; Osakada, G. et al. Highly absorptive curcumin improves left ventricular diastolic function regardless of blood pressure in hypertensive patients. J. Am. Coll. Cardiol.; 2012; 59, E987. [DOI: https://dx.doi.org/10.1016/S0735-1097(12)60988-7]

338. Phrommintikul, A.; Chanchai, R.; Wongcharoen, W. Effects of Curcuminoids on Myocardial Injury After Percutaneous Coronary Intervention. J. Med. Food; 2019; 22, pp. 680-684. [DOI: https://dx.doi.org/10.1089/jmf.2018.4321] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31045465]

339. Ramirez Bosca, A.; Carrion Gutierrez, M.A.; Soler, A.; Puerta, C.; Diez, A.; Quintanilla, E.; Bernd, A.; Miquel, J. Effects of the antioxidant turmeric on lipoprotein peroxides: Implications for the prevention of atherosclerosis. Age; 1997; 20, pp. 165-168. [DOI: https://dx.doi.org/10.1007/s11357-997-0015-z] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/23604308]

340. Shao, N.; Jia, H.; Li, Y.; Li, J. Curcumin improves treatment outcome of Takayasu arteritis patients by reducing TNF-alpha: A randomized placebo-controlled double-blind clinical trial. Immunol. Res.; 2017; 65, pp. 969-974. [DOI: https://dx.doi.org/10.1007/s12026-017-8917-z]

341. Wongcharoen, W.; Jai-Aue, S.; Phrommintikul, A.; Nawarawong, W.; Woragidpoonpol, S.; Tepsuwan, T.; Sukonthasarn, A.; Apaijai, N.; Chattipakorn, N. Effects of curcuminoids on frequency of acute myocardial infarction after coronary artery bypass grafting. Am. J. Cardiol.; 2012; 110, pp. 40-44. [DOI: https://dx.doi.org/10.1016/j.amjcard.2012.02.043]

342. Ara, S.A.; Mudda, J.; Lingappa, A.; Rao, P.; Zakaullah, S. Efficacy of curcumin in oral submucous fibrosis-A randomized controlled clinical trial. Int. J. Pharm. Sci. Res.; 2018; 9, pp. 5277-5286.

343. Chainani-Wu, N.; Collins, K.; Silverman, S., Jr. Use of curcuminoids in a cohort of patients with oral lichen planus, an autoimmune disease. Phytomedicine; 2012; 19, pp. 418-423. [DOI: https://dx.doi.org/10.1016/j.phymed.2011.11.005]

344. Chainani-Wu, N.; Madden, E.; Lozada-Nur, F.; Silverman, S., Jr. High-dose curcuminoids are efficacious in the reduction in symptoms and signs of oral lichen planus. J. Am. Acad. Dermatol.; 2012; 66, pp. 752-760. [DOI: https://dx.doi.org/10.1016/j.jaad.2011.04.022]

345. Chainani-Wu, N.; Silverman, S., Jr.; Reingold, A.; Bostrom, A.; Mc Culloch, C.; Lozada-Nur, F.; Weintraub, J. A randomized, placebo-controlled, double-blind clinical trial of curcuminoids in oral lichen planus. Phytomedicine; 2007; 14, pp. 437-446. [DOI: https://dx.doi.org/10.1016/j.phymed.2007.05.003] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/17604143]

346. Diana, H.; Cahyanto, A.; Amaliya, A.; Hardianto, A.; Maulina, T. The efficacy of curcuminoid in treating acute inflammation pain. Pain Pract.; 2018; 18, 80.

347. Kia, S.J.; Basirat, M.; Mortezaie, T.; Moosavi, M.S. Comparison of oral Nano-Curcumin with oral prednisolone on oral lichen planus: A randomized double-blinded clinical trial. BMC Complement. Med. Ther.; 2020; 20, 328. [DOI: https://dx.doi.org/10.1186/s12906-020-03128-7] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/33129289]

348. Kuriakose, M.A.; Ramdas, K.; Dey, B.; Iyer, S.; Rajan, G.; Elango, K.K.; Suresh, A.; Ravindran, D.; Kumar, R.R.; R, P. et al. A Randomized Double-Blind Placebo-Controlled Phase IIB Trial of Curcumin in Oral Leukoplakia. Cancer Prev. Res.; 2016; 9, pp. 683-691. [DOI: https://dx.doi.org/10.1158/1940-6207.CAPR-15-0390] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/27267893]

349. Lutfikadila, G.; Nurwiadh, A.; Cahyanto, A.; Amaliya, A.; Maulina, T. Effectiveness of curcuminoid dosage on inflammatory pain in acute periapical abscess. Pain Pract.; 2018; 18, 83.

350. Majeed, M.; Majeed, S.; Nagabhushanam, K. Efficacy and Safety of Tetrahydrocurcuminoids for the Treatment of Canker Sore and Gingivitis. Evid. Based Complement. Altern. Med.; 2020; 2020, 6611877. [DOI: https://dx.doi.org/10.1155/2020/6611877]

351. Malekzadeh, M.; Kia, S.J.; Mashaei, L.; Moosavi, M.S. Oral nano-curcumin on gingival inflammation in patients with gingivitis and mild periodontitis. Clin. Exp. Dent. Res.; 2020; 21, 21. [DOI: https://dx.doi.org/10.1002/cre2.330]

352. Maulina, T.; Diana, H.; Cahyanto, A.; Amaliya, A. The efficacy of curcumin in managing acute inflammation pain on the post-surgical removal of impacted third molars patients: A randomised controlled trial. J. Oral Rehabil.; 2018; 45, pp. 677-683. [DOI: https://dx.doi.org/10.1111/joor.12679]

353. Nct. A Clinical Study of Curcuminoids in the Treatment of Oral Lichen Planus. 2007; Available online: https://clinicaltrials.gov/show/nct00525421 (accessed on 20 February 2023).

354. Piyush, P.; Mahajan, A.; Singh, K.; Ghosh, S.; Gupta, S. Comparison of therapeutic response of lycopene and curcumin in oral submucous fibrosis: A randomized controlled trial. Oral Dis.; 2019; 25, pp. 73-79. [DOI: https://dx.doi.org/10.1111/odi.12947]

355. Rai, A.; Kaur, M.; Gombra, V.; Hasan, S.; Kumar, N. Comparative evaluation of curcumin and antioxidants in the management of oral submucous fibrosis. J. Investig. Clin. Dent.; 2019; 10, e12464. [DOI: https://dx.doi.org/10.1111/jicd.12464]

356. Rai, B.; Kaur, J.; Jacobs, R.; Singh, J. Possible action mechanism for curcumin in pre-cancerous lesions based on serum and salivary markers of oxidative stress. J. Oral Sci.; 2010; 52, pp. 251-256. [DOI: https://dx.doi.org/10.2334/josnusd.52.251]

357. Saran, G.; Umapathy, D.; Misra, N.; Channaiah, S.G.; Singh, P.; Srivastava, S.; Shivakumar, S. A comparative study to evaluate the efficacy of lycopene and curcumin in oral submucous fibrosis patients: A randomized clinical trial. Indian J. Dent. Res.; 2018; 29, pp. 303-312. [DOI: https://dx.doi.org/10.4103/ijdr.IJDR_551_16] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/29900913]

358. Yadav, M.; Aravinda, K.; Saxena, V.S.; Srinivas, K.; Ratnakar, P.; Gupta, J.; Sachdev, A.S.; Shivhare, P. Comparison of curcumin with intralesional steroid injections in Oral Submucous Fibrosis—A randomized, open-label interventional study. J. Oral Biol. Craniofacial Res.; 2014; 4, pp. 169-173. [DOI: https://dx.doi.org/10.1016/j.jobcr.2014.11.003]

359. Alvarenga, L.; Salarolli, R.; Cardozo, L.; Santos, R.S.; de Brito, J.S.; Kemp, J.A.; Reis, D.; de Paiva, B.R.; Stenvinkel, P.; Lindholm, B. et al. Impact of curcumin supplementation on expression of inflammatory transcription factors in hemodialysis patients: A pilot randomized, double-blind, controlled study. Clin. Nutr.; 2020; 39, pp. 3594-3600. [DOI: https://dx.doi.org/10.1016/j.clnu.2020.03.007] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/32204978]

360. Hami, M.; Bigdeli, A.; Khameneh Bagheri, R.; Rajabi, O.; Salehi, M.; Zahedi Avval, F. The effect of curcumin in prevention of contrast nephropathy following coronary angiography or angioplasty in CKD patients. Iran. J. Kidney Dis.; 2019; 13, pp. 304-309. [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31705746]

361. Jimenez-Osorio, A.S.; Garcia-Nino, W.R.; Gonzalez-Reyes, S.; Alvarez-Mejia, A.E.; Guerra-Leon, S.; Salazar-Segovia, J.; Falcon, I.; Montes de Oca-Solano, H.; Madero, M.; Pedraza-Chaverri, J. The Effect of Dietary Supplementation With Curcumin on Redox Status and Nrf2 Activation in Patients With Nondiabetic or Diabetic Proteinuric Chronic Kidney Disease: A Pilot Study. J. Ren. Nutr.; 2016; 26, pp. 237-244. [DOI: https://dx.doi.org/10.1053/j.jrn.2016.01.013]

362. Khajehdehi, P.; Pakfetrat, M.; Javidnia, K.; Azad, F.; Malekmakan, L.; Nasab, M.H.; Dehghanzadeh, G. Oral supplementation of turmeric attenuates proteinuria, transforming growth factor-beta and interleukin-8 levels in patients with overt type 2 diabetic nephropathy: A randomized, double-blind and placebo-controlled study. Scand. J. Urol. Nephrol.; 2011; 45, pp. 365-370. [DOI: https://dx.doi.org/10.3109/00365599.2011.585622] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/21627399]

363. Khajehdehi, P.; Zanjaninejad, B.; Aflaki, E.; Nazarinia, M.; Azad, F.; Malekmakan, L.; Dehghanzadeh, G.R. Oral supplementation of turmeric decreases proteinuria, hematuria, and systolic blood pressure in patients suffering from relapsing or refractory lupus nephritis: A randomized and placebo-controlled study. J. Ren. Nutr.; 2012; 22, pp. 50-57. [DOI: https://dx.doi.org/10.1053/j.jrn.2011.03.002]

364. Khosravi, A.; Hashemi, H.; Farahani, M.M.; Dolatkhah, M.; Rostami, Z.; Panahi, Y. The effects of curcumin on left ventricular function in patients with chronic renal failure. Arch. Cardiovasc. Imaging; 2015; 4, e38087. [DOI: https://dx.doi.org/10.5812/acvi.38087]

365. Pakfetrat, M.; Akmali, M.; Malekmakan, L.; Dabaghimanesh, M.; Khorsand, M. Role of turmeric in oxidative modulation in end-stage renal disease patients. Hemodial. Int.; 2015; 19, pp. 124-131. [DOI: https://dx.doi.org/10.1111/hdi.12204]

366. Pakfetrat, M.; Basiri, F.; Malekmakan, L.; Roozbeh, J. Effects of turmeric on uremic pruritus in end stage renal disease patients: A double-blind randomized clinical trial. J. Nephrol.; 2014; 27, pp. 203-207. [DOI: https://dx.doi.org/10.1007/s40620-014-0039-2]

367. Sabaghian, T.; Gheydari, M.E.; Divani, F. Evaluation of Curcumin (Turmeric Extract) Effect on Prevention of CIN in Patient Under Elective Coronary Angiography, a Randomized Double Blind Placebocontrolled Clinical Trial. Iran. J. Kidney Dis.; 2020; 14, pp. 198-205.

368. Samadian, F.; Dalili, N.; Poor-Reza Gholi, F.; Fattah, M.; Malih, N.; Nafar, M.; Firoozan, A.; Ahmadpoor, P.; Samavat, S.; Ziaie, S. Evaluation of Curcumin’s effect on inflammation in hemodialysis patients. Clin. Nutr. ESPEN; 2017; 22, pp. 19-23. [DOI: https://dx.doi.org/10.1016/j.clnesp.2017.09.006]

369. Trakarnvanich, T. SUN-025 Curcuminoids can prevent contrast-induced acute kidney injury in chronic kidney disease patients undergoing elective coronary procedures: A randomized controlled trial. Kidney Int. Rep.; 2020; 5, S215. [DOI: https://dx.doi.org/10.1016/j.ekir.2020.02.547]

370. Vafadar Afshar, G.; Rasmi, Y.; Yaghmaei, P.; Khadem-Ansari, M.H.; Makhdomii, K.; Rasooli, J. The Effects of Nano-curcumin Supplementation on Serum Level of hs-CRP, Adhesion Molecules, and Lipid Profiles in Hemodialysis Patients, A Randomized Controlled Clinical Trial. Iran. J. Kidney Dis.; 2020; 14, pp. 52-61. [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/32156842]

371. Vanaie, A.; Shahidi, S.; Iraj, B.; Siadat, Z.D.; Kabirzade, M.; Shakiba, F.; Mohammadi, M.; Parvizian, H. Curcumin as a major active component of turmeric attenuates proteinuria in patients with overt diabetic nephropathy. J. Res. Med. Sci.; 2019; 24, 77. [DOI: https://dx.doi.org/10.4103/jrms.JRMS_1055_18] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31523263]

372. Alizadeh, F.; Javadi, M.; Karami, A.A.; Gholaminejad, F.; Kavianpour, M.; Haghighian, H.K. Curcumin nanomicelle improves semen parameters, oxidative stress, inflammatory biomarkers, and reproductive hormones in infertile men: A randomized clinical trial. Phytother. Res.; 2018; 32, pp. 514-521. [DOI: https://dx.doi.org/10.1002/ptr.5998] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/29193350]

373. Ataei-Almanghadim, K.; Farshbaf-Khalili, A.; Ostadrahimi, A.R.; Shaseb, E.; Mirghafourvand, M. The effect of oral capsule of curcumin and vitamin E on the hot flashes and anxiety in postmenopausal women: A triple blind randomised controlled trial. Complement. Ther. Med.; 2020; 48, 102267. [DOI: https://dx.doi.org/10.1016/j.ctim.2019.102267] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31987231]

374. Fadinie, W.; Lelo, A.; Wijaya, D.W.; Lumbanraja, S.N. Curcumin’s Effect on COX-2 and IL-10 Serum in Preeclampsia’s Patient Undergo Sectio Caesarea with Spinal Anesthesia. Open Access Maced. J. Med. Sci.; 2019; 7, pp. 3376-3379. [DOI: https://dx.doi.org/10.3889/oamjms.2019.426] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/32002054]

375. Fadinie, W.; Lelo, A.; Wijaya, D.W.; Lumbanraja, S.N. Curcumin and its effect on preeclampsia: As anti-inflammatory, analgesic, and anticoagulant. Int. J. Curr. Pharm. Res.; 2020; 12, pp. 43-47. [DOI: https://dx.doi.org/10.22159/ijcpr.2020v12i2.37485]

376. Fanaei, H.; Khayat, S.; Kasaeian, A.; Javadimehr, M. Effect of curcumin on serum brain-derived neurotrophic factor levels in women with premenstrual syndrome: A randomized, double-blind, placebo-controlled trial. Neuropeptides; 2016; 56, pp. 25-31. [DOI: https://dx.doi.org/10.1016/j.npep.2015.11.003] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/26608718]

377. Hesami, S.; Kavianpour, M.; Rashidi Nooshabadi, M.; Yousefi, M.; Lalooha, F.; Khadem Haghighian, H. Randomized, double-blind, placebo-controlled clinical trial studying the effects of Turmeric in combination with mefenamic acid in patients with primary dysmenorrhoea. J. Gynecol. Obstet. Hum. Reprod.; 2020; 50, 101840. [DOI: https://dx.doi.org/10.1016/j.jogoh.2020.101840] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/32585392]

378. Rajuddin, R.; Wiweko, B.; Nugroho, L. The effects of curcumin administration on expression patterns of VEGF and COX-2 in fertile endometrium: A randomised clinical trial. Int. J. Appl. Pharm.; 2019; 11, pp. 149-152. [DOI: https://dx.doi.org/10.22159/ijap.2019.v11s6.33581]

379. Heshmati, J.; Golab, F.; Morvaridzadeh, M.; Potter, E.; Akbari-Fakhrabadi, M.; Farsi, F.; Tanbakooei, S.; Shidfar, F. The effects of curcumin supplementation on oxidative stress, Sirtuin-1 and peroxisome proliferator activated receptor gamma coactivator 1alpha gene expression in polycystic ovarian syndrome (PCOS) patients: A randomized placebo-controlled clinical trial. Diabetes Metab. Syndr. Clin. Res. Rev.; 2020; 14, pp. 77-82. [DOI: https://dx.doi.org/10.1016/j.dsx.2020.01.002]

380. Heshmati, J.; Moini, A.; Sepidarkish, M.; Morvaridzadeh, M.; Salehi, M.; Palmowski, A.; Mojtahedi, M.F.; Shidfar, F. Effects of curcumin supplementation on blood glucose, insulin resistance and androgens in patients with polycystic ovary syndrome: A randomized double-blind placebo-controlled clinical trial. Phytomedicine; 2021; 80, 153395. [DOI: https://dx.doi.org/10.1016/j.phymed.2020.153395]

381. Jamilian, M.; Foroozanfard, F.; Kavossian, E.; Aghadavod, E.; Shafabakhsh, R.; Hoseini, A.; Asemi, Z. Effects of curcumin on body weight, glycemic control and serum lipids in women with polycystic ovary syndrome: A randomized, double-blind, placebo-controlled trial. Clin. Nutr. ESPEN; 2020; 36, pp. 128-133. [DOI: https://dx.doi.org/10.1016/j.clnesp.2020.01.005]

382. Sohaei, S.; Amani, R.; Tarrahi, M.J.; Ghasemi-Tehrani, H. The effects of curcumin supplementation on glycemic status, lipid profile and hs-CRP levels in overweight/obese women with polycystic ovary syndrome: A randomized, double-blind, placebo-controlled clinical trial. Complement. Ther. Med.; 2019; 47, 102201. [DOI: https://dx.doi.org/10.1016/j.ctim.2019.102201]

383. The effect of curcuma on chest x-ray improvement and sputum coversion in patients with intensive phase treatment of pulmonary tuberculosis. Respirology; 2019; 24, 146.

384. Abidi, A.; Gupta, S.; Agarwal, M.; Bhalla, H.L.; Saluja, M. Evaluation of Efficacy of Curcumin as an Add-on therapy in Patients of Bronchial Asthma. J. Clin. Diagn. Res.; 2014; 8, pp. HC19-HC24. [DOI: https://dx.doi.org/10.7860/JCDR/2014/9273.4705]

385. Jusufovic, E.; Kosnik, M.; Jusufovic, A.; Becarevic, M.; Al-Ahmad, M.; Nurkic, J.; Osmic, M.; Nadarevic, A.; Petrak, F.; Halilovic, D. et al. Curcumin as an add-on therapy of moderate partially controlled asthma. Eur. Respir. J.; 2017; 50, 442. [DOI: https://dx.doi.org/10.1183/1393003.congress-2017.PA4695]

386. Jusufovic, E.; Kosnik, M.; Nurkic, J.; Arifhodzic, N.; Al-Ahmad, M.; Bulat-Kardum, L.; Becarevic, M.; Osmic, M.; Nadarevic, A.; Jusufovic, A. et al. Curcumin Improves Therapy of Moderate Partially Controlled Asthma: Placebo-controlled, single blind study. Eur. Respir. J.; 2019; 54, 2. [DOI: https://dx.doi.org/10.1183/13993003.congress-2019.PA2532]

387. Kim, D.H.; Phillips, J.F.; Lockey, R.F. Oral curcumin supplementation in patients with atopic asthma. Allergy Rhinol Provid.; 2011; 2, pp. e51-e53. [DOI: https://dx.doi.org/10.2500/ar.2011.2.0016]

388. Manarin, G.; Anderson, D.; Silva, J.M.E.; Coppede, J.D.S.; Roxo-Junior, P.; Pereira, A.M.S.; Carmona, F. Curcuma longa L. ameliorates asthma control in children and adolescents: A randomized, double-blind, controlled trial. J. Ethnopharmacol.; 2019; 238, 111882. [DOI: https://dx.doi.org/10.1016/j.jep.2019.111882] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/30991137]

389. Panahi, Y.; Ghanei, M.; Bashiri, S.; Hajihashemi, A.; Sahebkar, A. Short-term Curcuminoid Supplementation for Chronic Pulmonary Complications due to Sulfur Mustard Intoxication: Positive Results of a Randomized Double-blind Placebo-controlled Trial. Drug Res.; 2015; 65, pp. 567-573. [DOI: https://dx.doi.org/10.1055/s-0034-1389986] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/25268878]

390. Panahi, Y.; Ghanei, M.; Hajhashemi, A.; Sahebkar, A. Effects of Curcuminoids-Piperine Combination on Systemic Oxidative Stress, Clinical Symptoms and Quality of Life in Subjects with Chronic Pulmonary Complications Due to Sulfur Mustard: A Randomized Controlled Trial. J. Diet. Suppl.; 2016; 13, pp. 93-105. [DOI: https://dx.doi.org/10.3109/19390211.2014.952865] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/25171552]

391. Bilia, A.R.; Bergonzi, M.C.; Isacchi, B.; Antiga, E.; Caproni, M. Curcumin nanoparticles potentiate therapeutic effectiveness of acitrein in moderate-to-severe psoriasis patients and control serum cholesterol levels. J. Pharm. Pharmacol.; 2018; 70, pp. 919-928. [DOI: https://dx.doi.org/10.1111/jphp.12910] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/29600580]

392. Kurd, S.K.; Smith, N.; VanVoorhees, A.; Troxel, A.B.; Badmaev, V.; Seykora, J.T.; Gelfand, J.M. Oral curcumin in the treatment of moderate to severe psoriasis vulgaris: A prospective clinical trial. J. Am. Acad. Dermatol.; 2008; 58, pp. 625-631. [DOI: https://dx.doi.org/10.1016/j.jaad.2007.12.035]

393. Panahi, Y.; Sahebkar, A.; Parvin, S.; Saadat, A. A randomized controlled trial on the anti-inflammatory effects of curcumin in patients with chronic sulphur mustard-induced cutaneous complications. Ann. Clin. Biochem.; 2012; 49, pp. 580-588. [DOI: https://dx.doi.org/10.1258/acb.2012.012040]

394. Sahebkar, A.; Panahi, Y.; Amiri, M.; Davoudi, S.M.; Beiraghdar, F.; Hoseininejad, S.L.; Kolivand, M. Promising improvement of sulfur mustard-induced chronic pruritus, quality of life and antioxidant status by curcumin: Results of a randomized double-blind placebo-controlled trial. Clin. Biochem.; 2011; 44, S338. [DOI: https://dx.doi.org/10.1016/j.clinbiochem.2011.08.839]

395. Feig, J.L.; Wang, R.; Lim, H.; Wade, K.; Liu, H.; Fahey, J.; Chien, A.L.; Kang, S. The impact of oral phytochemicals on ultraviolet B-induced erythema response in human skin. J. Investig. Dermatol.; 2018; 138, S103. [DOI: https://dx.doi.org/10.1016/j.jid.2018.03.614]

396. Vaughn, A.R.; Clark, A.K.; Notay, M.; Sivamani, R.K. Randomized Controlled Pilot Study of Dietary Supplementation with Turmeric or Herbal Combination Tablets on Skin Barrier Function in Healthy Subjects. J. Med. Food; 2018; 20, 20. [DOI: https://dx.doi.org/10.1089/jmf.2018.0015]

397. Vaughn, A.R.; Pourang, A.; Clark, A.K.; Burney, W.; Sivamani, R.K. Dietary supplementation with turmeric polyherbal formulation decreases facial redness: A randomized double-blind controlled pilot study. J. Integr. Med.; 2019; 17, pp. 20-23. [DOI: https://dx.doi.org/10.1016/j.joim.2018.11.004]

398. Da Silva, T.A.L.; de Medeiros, D.C.; da Silva Cunha de Medeiros, R.C.; Medeiros, R.M.V.; de Souza, L.; de Medeiros, J.A.; Dos Santos, R.V.T.; de Alcantara Varela, P.W.; Leite-Lais, L.; Dantas, P.M.S. Influence of curcumin on glycemic profile, inflammatory markers, and oxidative stress in HIV-infected individuals: A randomized controlled trial. Phytother. Res.; 2020; 34, pp. 2323-2330. [DOI: https://dx.doi.org/10.1002/ptr.6683]

399. Karimi, A.; Mahmoodpoor, A.; Kooshki, F.; Niazkar, H.R.; Shoorei, H.; Tarighat-Esfanjani, A. Effects of nanocurcumin on inflammatory factors and clinical outcomes in critically ill patients with sepsis: A pilot randomized clinical trial. Eur. J. Integr. Med.; 2020; 36, 6. [DOI: https://dx.doi.org/10.1016/j.eujim.2020.101122]

400. Silva, T.A.L.; Medeiros, D.C.; Medeiros, G.; Medeiros, R.; de Souza Araujo, J.; Medeiros, J.A.; Ururahy, M.A.G.; Santos, R.V.T.; Medeiros, R.M.V.; Leite-Lais, L. et al. Influence of curcumin supplementation on metabolic and lipid parameters of people living with HIV/AIDS: A randomized controlled trial. BMC Complement. Altern. Med.; 2019; 19, 202. [DOI: https://dx.doi.org/10.1186/s12906-019-2620-7]

401. Valizadeh, H.; Abdolmohammadi-Vahid, S.; Danshina, S.; Ziya Gencer, M.; Ammari, A.; Sadeghi, A.; Roshangar, L.; Aslani, S.; Esmaeilzadeh, A.; Ghaebi, M. et al. Nano-curcumin therapy, a promising method in modulating inflammatory cytokines in COVID-19 patients. Int. Immunopharmacol.; 2020; 89, 107088. [DOI: https://dx.doi.org/10.1016/j.intimp.2020.107088]

402. Allegri, P.; Rissotto, R.; Rissotto, F.; Masala, A.; Crivelli, M.G.; Blanco, A.R.; Murialdo, U. Evaluation of the anti-inflammatory efficacy of high oral bioavailability Curcumin as addon treatment in non-infectious uveitic cystoid macular edema by SD-OCT and OCT-Angiography: Preliminary results. Investig. Ophthalmol. Vis. Sci.; 2020; 61, 5356.

403. Allegri, P.; Mastromarino, A.; Neri, P. Management of chronic anterior uveitis relapses: Efficacy of oral phospholipidic curcumin treatment. Long-term follow-up. Clin. Ophthalmol.; 2010; 4, pp. 1201-1206. [DOI: https://dx.doi.org/10.2147/OPTH.S13271]

404. Ferrara, M.; Allegrini, D.; Sorrentino, T.; Sborgia, G.; Parmeggiani, F.; Borgia, A.; Romano, M.R. Curcumin-Based Treatment for Macular Edema from Uncommon Etiologies: Efficacy and Safety Assessment. J. Med. Food; 2020; 23, pp. 834-840. [DOI: https://dx.doi.org/10.1089/jmf.2019.0241] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31913752]

405. Lal, B.; Kapoor, A.K.; Asthana, O.P.; Agrawal, P.K.; Prasad, R.; Kumar, P.; Srimal, R.C. Efficacy of curcumin in the management of chronic anterior uveitis. Phytother. Res.; 1999; 13, pp. 318-322. [DOI: https://dx.doi.org/10.1002/(SICI)1099-1573(199906)13:4<318::AID-PTR445>3.0.CO;2-7]

406. Kalpravidh, R.W.; Siritanaratkul, N.; Insain, P.; Charoensakdi, R.; Panichkul, N.; Hatairaktham, S.; Srichairatanakool, S.; Phisalaphong, C.; Rachmilewitz, E.; Fucharoen, S. Improvement in oxidative stress and antioxidant parameters in beta-thalassemia/Hb E patients treated with curcuminoids. Clin. Biochem.; 2010; 43, pp. 424-429. [DOI: https://dx.doi.org/10.1016/j.clinbiochem.2009.10.057] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/19900435]

407. Mohammadi, E.; Tamaddoni, A.; Qujeq, D.; Nasseri, E.; Zayeri, F.; Zand, H.; Gholami, M.; Mir, S.M. An investigation of the effects of curcumin on iron overload, hepcidin level, and liver function in beta-thalassemia major patients: A double-blind randomized controlled clinical trial. Phytother. Res.; 2018; 32, pp. 1828-1835. [DOI: https://dx.doi.org/10.1002/ptr.6118]

408. Nasseri, E.; Mohammadi, E.; Tamaddoni, A.; Qujeq, D.; Zayeri, F.; Zand, H. Benefits of Curcumin Supplementation on Antioxidant Status in beta-Thalassemia Major Patients: A Double-Blind Randomized Controlled Clinical Trial. Ann. Nutr. Metab.; 2017; 71, pp. 136-144. [DOI: https://dx.doi.org/10.1159/000479634]

409. Tamaddoni, A.; Nasseri, E.; Mohammadi, E.; Qujeq, D.; Zayeri, F.; Zand, H.; Mir, S.M.; Gholami, M. A Double-blind Randomized Controlled Trial of Curcumin for Improvement in Glycemic Status, Lipid Profile and Systemic Inflammation in β-Thalassemia Major. J. Herb. Med.; 2020; 21, 100324. [DOI: https://dx.doi.org/10.1016/j.hermed.2019.100324]

410. Biswas, J.; Sinha, D.; Mukherjee, S.; Roy, S.; Siddiqi, M.; Roy, M. Curcumin protects DNA damage in a chronically arsenic-exposed population of West Bengal. Hum. Exp. Toxicol.; 2010; 29, pp. 513-524. [DOI: https://dx.doi.org/10.1177/0960327109359020] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/20056736]

411. Falgiano, P.A.; Gillum, T.L.; Schall, Z.J.; Strag, H.R.; Kuennen, M.R. Dietary curcumin supplementation does not alter peripheral blood mononuclear cell responses to exertional heat stress. Eur. J. Appl. Physiol.; 2018; 118, pp. 2707-2717. [DOI: https://dx.doi.org/10.1007/s00421-018-3998-5] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/30276476]

412. Klickovic, U.; Doberer, D.; Gouya, G.; Aschauer, S.; Weisshaar, S.; Storka, A.; Bilban, M.; Wolzt, M. Human pharmacokinetics of high dose oral curcumin and its effect on heme oxygenase-1 expression in healthy male subjects. Biomed Res. Int.; 2014; 2014, 458592. [DOI: https://dx.doi.org/10.1155/2014/458592] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/24592391]

413. Laine, F.; Laviolle, B.; Bardou-Jacquet, E.; Fatih, N.; Jezequel, C.; Collet, N.; Ropert, M.; Morcet, J.; Hamon, C.; Reymann, J.M. et al. Curcuma decreases serum hepcidin levels in healthy volunteers: A placebo-controlled, randomized, double-blind, cross-over study. Fundam. Clin. Pharmacol.; 2017; 31, pp. 567-573. [DOI: https://dx.doi.org/10.1111/fcp.12288] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/28370178]

414. Peron, G.; Sut, S.; Dal Ben, S.; Voinovich, D.; Dall’Acqua, S. Untargeted UPLC-MS metabolomics reveals multiple changes of urine composition in healthy adult volunteers after consumption of curcuma longa L. extract. Food Res. Int. Ott. Ont.; 2020; 127, 108730. [DOI: https://dx.doi.org/10.1016/j.foodres.2019.108730] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31882111]

415. Rai, B.; Kaur, J.; Catalina, M. Anti-oxidation actions of curcumin in two forms of bed rest: Oxidative stress serum and salivary markers. Asian Pac. J. Trop. Med.; 2010; 3, pp. 651-654. [DOI: https://dx.doi.org/10.1016/S1995-7645(10)60157-5]

416. Roy, M.; Sinha, D.; Mukherjee, S.; Biswas, J. Curcumin prevents DNA damage and enhances the repair potential in a chronically arsenic-exposed human population in West Bengal, India. Eur. J. Cancer Prev.; 2011; 20, pp. 123-131. [DOI: https://dx.doi.org/10.1097/CEJ.0b013e328341017a] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/21332098]

417. Satoskar, R.R.; Shah, S.J.; Shenoy, S.G. Evaluation of anti-inflammatory property of curcumin (diferuloyl methane) in patients with postoperative inflammation. Int. J. Clin. Pharmacol. Ther. Toxicol.; 1986; 24, pp. 651-654. [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/3546166]

418. Wu, S.; Xiao, D. Effect of curcumin on nasal symptoms and airflow in patients with perennial allergic rhinitis. Ann. Allergy Asthma Immunol.; 2016; 117, pp. 697-702. [DOI: https://dx.doi.org/10.1016/j.anai.2016.09.427] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/27789120]

419. Page, M.J.; Higgins, J.P.; Clayton, G.; Sterne, J.A.; Hróbjartsson, A.; Savović, J. Empirical Evidence of Study Design Biases in Randomized Trials: Systematic Review of Meta-Epidemiological Studies. PLoS ONE; 2016; 11, e0159267. [DOI: https://dx.doi.org/10.1371/journal.pone.0159267]

420. Kaptchuk, T.J. The double-blind, randomized, placebo-controlled trial: Gold standard or golden calf?. J. Clin. Epidemiol.; 2001; 54, pp. 541-549. [DOI: https://dx.doi.org/10.1016/S0895-4356(00)00347-4]

421. Apridonidze, T.; Essah, P.A.; Iuorno, M.J.; Nestler, J.E. Prevalence and characteristics of the metabolic syndrome in women with polycystic ovary syndrome. J. Clin. Endocrinol. Metab.; 2005; 90, pp. 1929-1935. [DOI: https://dx.doi.org/10.1210/jc.2004-1045]

422. Furman, D.; Campisi, J.; Verdin, E.; Carrera-Bastos, P.; Targ, S.; Franceschi, C.; Ferrucci, L.; Gilroy, D.W.; Fasano, A.; Miller, G.W. et al. Chronic inflammation in the etiology of disease across the life span. Nat. Med.; 2019; 25, pp. 1822-1832. [DOI: https://dx.doi.org/10.1038/s41591-019-0675-0]

423. Saltiel, A.R.; Olefsky, J.M. Inflammatory mechanisms linking obesity and metabolic disease. J. Clin. Investig.; 2017; 127, pp. 1-4. [DOI: https://dx.doi.org/10.1172/JCI92035]

424. Davis, M.A.; Ettinger, W.H.; Neuhaus, J.M. Obesity and osteoarthritis of the knee: Evidence from the National Health and Nutrition Examination Survey (NHANES I). Semin. Arthritis Rheum.; 1990; 20, pp. 34-41. [DOI: https://dx.doi.org/10.1016/0049-0172(90)90045-H]

425. Rücker, G.; Carpenter, J.R.; Schwarzer, G. Detecting and adjusting for small-study effects in meta-analysis. Biom. J.; 2011; 53, pp. 351-368. [DOI: https://dx.doi.org/10.1002/bimj.201000151]

426. Centers for Disease Control and Prevention. Adult Obesity Facts. Available online: https://www.cdc.gov/obesity/data/adult.html (accessed on 31 January 2023).

427. Centers for Disease Control and Prevention. Prevalence of Prediabetes Among Adults. Available online: https://www.cdc.gov/diabetes/data/statistics-report/prevalence-of-prediabetes.html (accessed on 31 January 2023).

428. Centers for Disease Control and Prevention. National Diabetes Statistics Report. Available online: https://www.cdc.gov/diabetes/data/statistics-report/index.html (accessed on 31 January 2023).

429. Xu, Y.; Wu, Q. Trends and disparities in osteoarthritis prevalence among US adults, 2005–2018. Sci. Rep.; 2021; 11, 21845. [DOI: https://dx.doi.org/10.1038/s41598-021-01339-7] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/34750468]

430. Lou, Y.; Zheng, J.; Hu, H.; Lee, J.; Zeng, S. Application of ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry to identify curcumin metabolites produced by human intestinal bacteria. J. Chromatogr. B; 2015; 985, pp. 38-47. [DOI: https://dx.doi.org/10.1016/j.jchromb.2015.01.014] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/25658514]

431. Howells, L.; Malhotra Mukhtyar, R.; Theofanous, D.; Pepper, C.; Thomas, A.; Brown, K.; Khan, S. A Systematic Review Assessing Clinical Utility of Curcumin with a Focus on Cancer Prevention. Mol. Nutr. Food Res.; 2021; 65, e2000977. [DOI: https://dx.doi.org/10.1002/mnfr.202000977] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/34015183]