PLATINUM TURMERIC BIOCEUTICAL SUPPLEMENT
Platinum Turmeric Bioceutical Supplement Capsules
Platinum Turmeric Product Information
- Serving Size: 2 Capsules
- Capsules Per Container: 60
- Bottle Color: White
- Lid Color: Black
Curcumin (Turmeric extract)
A massive portfolio of cell biology and medical research over the past half century has shown that curcumin, the primary biologically-active component of the golden spice turmeric, can influence multiple cell signaling pathways and disease states. Extensive clinical trials over the past 25 years have interrogated the pharmacokinetics, safety, and efficacy of this bioceutical against numerous diseases in humans. Although our Platinum Turmeric is formulated primarily for hip and joint disorder relief, there are nevertheless extensive clinical benefits observed in patients with various diseases of multi-faceted etiologies including, but not limited to:
- Cancer , , –, –,
- Cardiovascular disease (including acute coronary syndrome) –
- Neurodegeneration –
- Arthritis –
- Crohn’s disease, colitis, and IBS 
- Pancreatitis –
- Peptic and gastric ulcers (and gastric inflammation) –
- Diabetes 
- Alcohol-induced liver damage –
The global interest in curcumin research has increased dramatically over the last 20 years. There are currently more than 5000 articles on curcumin listed in the National Institutes of Health database. This natural plant polyphenol has been shown to possess activities in animal models of many human diseases. In human trials, curcumin has been found to be safe and efficacious and the US Food and Drug Administration has approved curcumin as a ‘generally regarded as safe’ compound.
Although curcumin has shown therapeutic efficacy against many human ailments, one of the original problems with curcumin was its poor bioavailability , which appears to be due primarily to low absorption, unfavorable metabolism and rapid elimination in urine. Therefore, extensive efforts have been made to increase the bioavailability of curcumin, primarily by improving its absorption. Intriguingly, in humans receiving a dose of 2g curcumin alone, blood serum levels were recorded as barely detectable, but co-administration of BioPerine led to a 2000% increase in the bioavailability of curcumin . Even better, the effect of BioPerine in enhancing the bioavailability of curcumin has recently been revealed to be much greater in humans than previously thought .
The tolerability, safety, and nontoxicity of curcumin, even at very high doses, are now well established by clinical trials addressing a wide range of human diseases ,  . Doses of curcumin as high as 8 g/day in combination is well-tolerated , . Thus far, the clinical trials conducted have revealed the therapeutic potential of curcumin against a wide range of conditions. In clinical trials assessing the anti-inflammatory and liver protecting ability of curcumin, it has been used either alone or in combination with other antioxidant compounds including quercetin, BioPerine, soy isoflavones, mesalamine, prednisone, lactoferrin, and N-acetylcysteine (NAC).
As of late 2019, results from over 80 clinical trials have been published, and an additional 28 clinical trials are still in progress.
Selected Clinical Findings
- “A Randomized, Pilot Study to Assess the Efficacy and Safety of Curcumin in Patients with Active Rheumatoid Arthritis” 
Curcumin is known to possess potent anti-inflammatory and anti-arthritic properties. This pilot clinical study evaluated the safety and effectiveness of curcumin alone, and in combination with diclofenac sodium in patients with active rheumatoid arthritis (RA). Forty‐five patients diagnosed with RA were randomized into three groups with patients receiving curcumin (500 mg) and diclofenac sodium (50 mg) alone or their combination. The primary endpoints were reduction in Disease Activity Score (DAS) 28. The secondary endpoints included American College of Rheumatology (ACR) criteria for reduction in tenderness and swelling of joint scores. Patients in all three treatment groups showed statistically significant changes in their DAS scores. Interestingly, the curcumin group showed the highest percentage of improvement in overall DAS and ACR scores (ACR 20, 50 and 70) and these scores were significantly better than the patients in the diclofenac sodium group. More importantly, curcumin treatment was found to be safe and did not relate with any adverse events. Our study provides the first evidence for the safety and superiority of curcumin treatment in patients with active RA, and highlights the need for future large‐scale trials to validate these findings in patients with RA and other arthritic conditions.
The primary objective of this study was to determine the efficacy of curcumin with or without diclofenac sodium (a nonsteroidal anti-inflammatory drug or NSAID) in patients with rheumatoid arthritis (RA). Since the study was fairly small, it necessitated being an open labelled study. The results from this 8‐week randomized study in patients with active RA clearly show that curcumin is safe, and has a significant efficacy in improving the Disease Activity Score and tenderness/swelling scores in patients with mild or moderate RA, when given alone or in combination with an NSAID. In fact, patients who received curcumin achieved higher tenderness/swelling reduction than the other two groups. For all treatment groups, the tenderness/swelling reduction was significant. All components of tenderness/swelling, namely total number of painful joints, total swollen joints, patient's GA, physician's global assessment, disability index and patients’ own health assessment questionnaire showed significant changes in all three groups. It is noteworthy that the C-reactive protein showed significant improvement only in the curcumin group. C-reactive protein (CRP) is a protein made by the liver; levels in the blood increase when there is a condition causing inflammation somewhere in the body. Consistent with this, the curcumin group showed the most significant improvement in the Disease Activity Scores.
The findings of this study are significant, as they demonstrate that curcumin was not only safe and effective, but was surprisingly more effective in alleviating pain compared with a standard-of-care NSAID. These findings are consistent with a previously published report which demonstrated the safety and efficacy of curcumin for the treatment of patients with knee osteoarthritis . These investigators reported not only that both curcumin and ibuprofen had comparable efficacy in mitigating the clinical symptoms for osteoarthritis, but also that the rate of adverse events with curcumin was lower than that of ibuprofen (~30% in curcumin group versus ~45% in the ibuprofen group), an observation that has been independently validated in these patients with rheumatoid arthritis. Although the molecular mechanisms for such efficacy of curcumin are unclear, it is reasonable to speculate that curcumin may differentially regulate molecular targets that control chronic pain versus the ones that mediate acute pain.
Curcumin has also been reported to be effective in alleviating chronic pain in different experimental models including neuropathic pain, one of the most difficult forms of pain to treat –. In this study, however, curcumin + NSAID combination was slightly less efficacious than curcumin alone, even though the curcumin dose remained unchanged. On the contrary, the NSAID group experienced several adverse events that were probably a direct consequence of the use of this drug. Supplementation of curcumin alone provided significant overall improvement in patients with active RA, and this efficacy was better than that provided by NSAIDs, and was not associated with any adverse events. These findings are of further interest considering that although curcumin has long been known to possess a wide spectrum of activities including antioxidant, anti-inflammatory and anticancer properties in different preclinical and clinical models, the poor absorption and bioavailability of this phytonutrient has severely limited its application to various diseases. In this study, the researchers were able to overcome this shortcoming by using a preparation of curcumin that contained BioPerine just like Umbrella Labs’ formulation. These observations that curcumin alone was able to alleviate symptoms of rheumatoid arthritis in this study are quite encouraging, and these results provide an ideal springboard for investigating the potential of curcumin in other chronic diseases arising in the setting of dysregulated chronic inflammation.
In conclusion, curcumin was generally safe and well‐tolerated in most subjects when given up to 8 weeks. Although these data are very encouraging they are a platform only for future planning of long‐term studies with the drug in combination with existing standard therapies in RA, which will provide a complete picture of the utility of curcumin. Curcumin has activities similar to anti‐TNF drugs (eg. Remicade, Humira, Enbrel, etc) but without their serious side‐effects and a study comparing these two drugs is warranted. Taken together, these results provide a clear proof‐of‐principle for the superiority of curcumin, and the lack of any synergistic or additive efficacy when used in conjunction with NSAIDS strongly favors the safe and effective application of curcumin alone in clinical settings for the management of rheumatoid arthritis, and other pro-inflammatory diseases including cancer in the future.
- “Curcumin and cognition: a randomised, placebo-controlled, double-blind study of community-dwelling older adults” 
Curcumin therapy in animals has produced positive cognitive and behavioral outcomes; results of human trials, however, have been inconsistent. In this study, we report the results of a 12-month, randomized, placebo-controlled, double-blind study that investigated the ability of a curcumin formulation to prevent cognitive decline in a population of community-dwelling older adults. Individuals (n=96) ingested either placebo or 1500 mg/d Curcumin for 12 months. A battery of clinical and cognitive measures was administered at baseline and at the 6-month and 12-month follow-up assessments. A significant time × treatment group interaction was observed for the Montreal Cognitive Assessment. Subsequent analysis revealed that this association was driven by a decline in cognitive function of the placebo group at 6 months that was not observed in the curcumin treatment group. No differences were observed between the groups for all other clinical and cognitive measures. Our findings suggest that further longitudinal assessment is required to investigate changes in cognitive outcome measures, ideally in conjunction with biological markers of neurodegeneration.
- “Investigation of the effects of solid lipid curcumin on cognition and mood in a healthy older population” 
Curcumin possesses many properties which may prevent or ameliorate pathological processes underlying age-related cognitive decline, dementia or mood disorders. These benefits in preclinical studies have not been established in humans. This randomized, double-blind, placebo-controlled trial examined the acute (1 and 3 h after a single dose), chronic (4 weeks) and acute-on-chronic (1 and 3 h after single dose following chronic treatment) effects of a curcumin formulation on cognitive function, mood and blood biomarkers in 60 healthy adults aged 60–85. One hour after administration curcumin significantly improved performance on sustained attention and working memory tasks, compared with placebo. Working memory and mood (general fatigue and change in state calmness, contentedness and fatigue induced by psychological stress) were significantly better following chronic treatment. A significant acute-on-chronic treatment effect on alertness and contentedness was also observed. Curcumin was associated with significantly reduced total and LDL cholesterol and had no effect on hematological safety measures. To our knowledge this is the first study to examine the effects of curcumin on cognition and mood in a healthy population or to examine any acute behavioral effects in humans. Results highlight the need for further investigation of the potential psychological and cognitive benefits of curcumin in an older population.
Effect of chronic treatment on change in mood following mental challenge at Follow-Up, Pre-Dose assessment. *p < 0.05.
Lipid measures significantly affected by chronic treatment. *p < 0.05.
This randomized, double-blind, placebo-controlled, parallel-groups trial sought to investigate the effects of acute, chronic and acute-on-chronic curcumin treatment on cognition, mood and ability to cope with mental challenge in healthy older adults. The study had an excellent retention rate, with 100% of participants who received treatment completing the trial. However, it was not without limitations; the low levels of depression, anxiety, stress and inflammatory cytokines exhibited by participants at both testing sessions prevented the planned examinations of these measures.
Compared with placebo, a single curcumin dose acutely improved performance on the digit vigilance task, a measure of sustained attention, and the serial three subtraction task, a measure of working memory. Performance of the serial three subtraction task was also improved by 4 weeks of curcumin treatment. Performance of the serial three subtraction tasks primarily relies on working memory and also reflects psychomotor speed and attention but places little demand on executive function. These results suggest that working memory and sustained attention were the cognitive processes most enhanced by curcumin.
Working memory is a particularly important target for potential cognitive enhancers in the elderly as it is known to decline in normal healthy aging and may underlie age-related changes in other cognitive functions. Further deficits in working memory are seen in multiple types of dementia. Therefore the preservation or enhancement of working memory may aid in preventing or reversing age-related memory impairments or dementia risk. While mechanistic data on the cognitive effects of curcumin in healthy humans is lacking, animal studies indicate that curcumin is able to inhibit monoamine oxidase (MAO) and increase serotonin and dopamine levels 1 h after administration . Similar enhancement of these neurotransmitter systems has also been reported 24 h after the cessation of chronic curcumin treatment. Monoamines, dopamine in particular, are known to be involved in working memory. Dopamine release is increased during working memory and attention tasks in healthy adults and correlates with task performance. It could therefore be hypothesized that the observed improvements in cognitive task performance following acute and chronic treatment were due to the effect of curcumin on monoaminergic neurotransmission. However, further studies of the effects of curcumin on neurotransmitters (and other biomarkers) in humans and the time course of these effects are required to verify this.
Four weeks of chronic curcumin treatment was found to significantly reduce fatigue during the week preceding the Follow-Up session compared with placebo. It also improved resilience to the detrimental impact of cognitive stress on mood. Compared with placebo, curcumin was associated with a lesser reduction in calmness and contentedness and an inhibition of increased fatigue following mental challenge. This benefit was observed both immediately following mental challenge and over the duration of the testing session. A single acute-on-chronic dose of curcumin further protected against reductions in alertness and contentedness induced by performance of the cognitive array.
The effects of curcumin on fatigue have not been well investigated but it is known to possess a number of health-promoting properties which could have produced the observed reduction in fatigue. For example, in the present study curcumin was associated with lower levels of total and LDL cholesterol (ie. bad cholesterol); anti-fatigue effects have previously been reported for other cholesterol-lowering supplements . Also though not examined here, curcumin is able to reduce oxidative stress, which has been associated with symptoms of fatigue. In addition, curcumin also functions to combat fatigue by improving the maintenance of energy levels and ability to meet energy demands through its effects on mitochondrial function, AMP-activated protein kinase .
Greater negative reactivity to stressors has been linked with depression and anxiety symptoms, risk and disorders. Thus, by mitigating the affective impact of psychological stress on mood, curcumin may have the potential to reduce vulnerability to depression and anxiety disorders. This is consistent with animal studies which have demonstrated antidepressant and neurotransmitter-enhancing effects of curcumin in stress-induced models of depression , .
Regardless of how the observed mood-enhancing effects of curcumin were achieved, they support its potential for the prevention of fatigue and affective disorders, such as depression and anxiety, which are particularly important in a middle-aged adults where these conditions may have serious detrimental consequences. Fatigue, anxiety and depression among older adults have each been associated with decline in physical function and ability to perform activities of daily living. Fatigue is additionally associated with poorer self-rated health, and greater loneliness.
The precise mechanisms underlying the above effects are not currently known. Future research might usefully include measurement of the curcumin parent molecule or its metabolites to allow examination of the relationship between absorption/bioavailability and behavioral changes. Similarly, as blood samples were collected only once per visit, the biochemical results reflect the overall effects of 4 weeks of chronic treatment. The authors therefore cannot discern when during the intervention period the behavioral or biochemical changes (i.e. cholesterol reduction) emerged or indeed whether there were acute biochemical changes that were not measured.
This was the first study to examine the effects of curcumin on cognition in a healthy population or to examine any acute behavioral effects of curcumin in humans. Hematological safety measures confirmed that 4 weeks of daily treatment with 400 mg of curcumin was safe and well tolerated all patients. Behavioral measures showed that even at the low dose implemented here (approximately 80 mg) curcumin has the potential to improve important cognitive functions, reduce fatigue and improve resilience to the detrimental effects of psychological stress on mood. In doing so it highlights the need for further investigation of the potential psychological benefits of curcumin in other discrete populations.
Glucosamine sulfate and chondroitin sulfate
Glucosamine and chondroitin sulfate are natural compounds that have both been shown to delay arthritis progression in several clinical trials. This is especially important since arthritis is the most prevalent form of joint disease and a growing cause of disability worldwide. Globally, 20% of women and 10% of men will eventually have symptomatic arthritis, and 30% of these individuals will be unable to perform routine daily activities; in the US the numbers are almost double: By 2050, it is projected that over 125 million people will suffer from arthritis, which necessitates costly medical intervention , .
Selected clinical findings
- “Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial” 
We did a randomised, double-blind placebo controlled trial, in which 212 patients with knee osteoarthritis were randomly assigned 1500 mg glucosamine sulfate or placebo once daily for 3 years. Weight-bearing radiographs of each knee in full extension were taken at enrolment and after 1 and 3 years. Mean joint-space width of the medial compartment of the tibiofemoral joint was assessed by digital image analysis, whereas minimum joint-space width—ie, at the narrowest point—was measured by visual inspection with a magnifying lens. Symptoms were scored by the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index.
WOMAC= Western Ontario and MacMaster Arthritis Index
VAS= Visual analog scale
Previous short-term clinical studies have shown glucosamine sulfate is safe—even more so than standard NSAID (such as ibuprofen), especially concerning the gastrointestinal tract , . This study not report any significant differences from placebo in safety, with no distinct adverse event pattern. Similarly, routine laboratory tests did not show any general system modification nor metabolic changes.
- “Combined chondroitin sulfate and glucosamine for painful knee osteoarthritis: a multicentre, randomised, double-blind, non-inferiority trial versus celecoxib (Celebrex)” 
Osteoarthritis is the most common form of arthritis in Western populations. It most frequently affects the knee, causing joint pain, tenderness, limitations of movement and impairment of quality of life, resulting in a social and economic burden. It accounts for a substantial number of healthcare visits and costs in populations with access to medical care. With increasing life expectancy, osteoarthritis is anticipated to become the fourth leading cause of disability by the year 2020. Standard treatment focuses on symptom relief with analgesics and non-steroidal anti-inflammatory drugs (NSAIDs like ibuprofen or Celebrex), though the latter can cause serious gastrointestinal and cardiovascular adverse effects, leading to concerns over long-term use.
Fig. 1. Results showing no difference between chondroitin+glucosamine VERSUS Celebrex after 180 days of use
- WOMAC pain score
- WOMAC stiffness score
- WOMAC joint function score
- Visual analog scale (ie. how much joint movement)
CS+GH = chondroitin sulfate and glucosamine
CE = Celebrex (a prescription NSAID)
This clinical trial found that a fixed-dose combination of chondroitin sulfate plus glucosamine has comparable efficacy to Celebrex in reducing pain in patients with osteoarthritis of the knee with moderate-to-severe pain after 6 months of treatment. The reduction in pain was both clinically important and statistically significant (50% reduction in both groups), as was the improvement in stiffness (47% reduction with the combination vs 50% with celecoxib), and function (46% vs 46%, respectively). Similar improvements were seen in visual analogue scale, the pain/discomfort dimension of patients’ and investigators’ assessments of disease activity and response to therapy without differences between treatments. Other clinical symptoms, such as swelling/effusion, improved to the same extent in both groups.
Chondroitin sulfate and glucosamine have a slightly slower onset of response yet provide long-lasting pain relief and functional improvement in arthritis. In the current study, Celebrex was superior to chondroitin sulfate and glucosamine at 1–4 months (in terms of WOMAC scores and Huskisson's visual analogue scale), but by 6 months, response to chondroitin sulfate and glucosamine was similar to Celebrex .Other studies have already demonstrated anti-inflammatory effects of both glucosamine and chondroitin sulfate. Both inhibit metalloproteinase activity, prostaglandin E2 release, nitric oxide production and degradation of glycosaminoglycans, as well as stimulate the synthesis of hyaluronic acid in the joint . Chondroitin sulfate stimulates collagen synthesis, while glucosamine inhibits prostaglandin release. However, while each substance exerts beneficial effects on the processes underlying osteoarthritis, a number of studies have demonstrated that many of these effects benefit from the synergy observed with combined glucosamine and chondroitin sulfate treatment –.
In contrast, Celebrex only inhibits prostaglandin biosynthesis, primarily through blocking the cyclooxygenase-2 enzyme, thereby achieving rapid reduction in signs and symptoms of osteoarthritis of the knee. However, Celebrex does not alter other processes underlying the disease. This difference in the mechanisms of action is supported by the present results, which indicate more substantial and faster response for celecoxib than for chondroitin sulfate plus glucosamine up to 120 days, but by 6 months there are no significant differences between the two treatments across all outcomes. Indeed, the overall pain improvement calculated using area under the curve analyses was superior with celecoxib than with the combination.
Both treatments had a good safety profile and tolerability in this population, which excluded patients with high cardiovascular or gastrointestinal risk. Celebrex is recognized to increase the risk of cardiovascular thrombotic events, congestive heart failure and major gastrointestinal events compared with placebo . In fact in the European Union, Celebrex is not even allowed to be prescribed in patients with known cardiovascular and peripheral vascular disease. Thus, it is obvious that the combination of glucosamine and chondroitin offers a superior alternative for arthritis.
Boswellia serrata is a tree which grows in the hilly, temperate regions of India. The prized resin extracted from the tree possess excellent anti-inflammatory, anti-arthritis and pain relief activity, which has been shown to significantly reducing the total inflammatory blood cell count in joint fluid, thus restoring the integrity of blood vessels obliterated by arthritic spasm or chronic damage.
- “Efficacy and tolerability of Boswellia extract in treatment of osteoarthritis of knee: A randomized double blind placebo controlled trial” 
Patients above the age of 40 years of either gender, with clinical/radiological osteoarthritis of knee, taking physiotherapy or any NSAIDs, were identified and approached to participate in the study. Before starting, and at the end of first intervention as well as second intervention, the patients were asked to grade the pain intensity, loss of function and swelling. Radiographs were also taken at these points. Washout period of 21 days was given at the end of first intervention to ensure that the residual effect of the first intervention did not linger and affect the second one. After washout, the crossover was done, with each patient getting opposite of the previous intervention. The observations were decoded, tabulated and then analyzed.
The mean scores for the efficacy obtained at the baseline and after eight weeks of the first intervention are presented above. The decrease in severity of pain and swelling and improvement in the loss of function were clinically and statistically significant in the group receiving the active drug as compared to the group receiving the placebo. At the second intervention after crossover, the patients showed worsening of the above parameters in the group receiving the placebo and vice versa in the patient receiving the drug. There was no remarkable variation between the efficacy at the beginning of the first intervention and after crossover at the beginning of the second intervention.
NSAIDs can cause disruption of glycosaminoglycan synthesis, which can accelerate the articular damage in arthritic conditions. However, Boswellia extract has been shown to decrease glycosaminoglycan degradation in joints, which helps to maintain cartilage in good condition. This might be responsible for the recovery of the patients with arthritis and might slow or stop progression of this painful condition.
Ginger is a medicinal plant from Zingiberaceae family. To date over 45 antioxidants have been isolated from ginger rhizome. The major pharmacological activity of ginger is related to its phenolic ingredients such as gingerols and shogaols: these compounds have anti-emetic (anti-nausea), anti-fever, anti-cough, anti-inflammatory, anti-diabetic, anti-hyperlipidemic (anti-high fat), and anti-cancer properties , . Ginger is known as a traditional treatment for relieving stiffness and pain in patients with osteoarthritis, and it is a safe and well tolerated in doses up to 2 g daily , . However until recently there was insufficient clinical evidence for the efficacy of ginger in the treatment of arthritis.
- “The effect of ginger supplementation on some immunity and inflammation intermediate genes expression in patients with active Rheumatoid Arthritis” 
In this randomized, double-blind placebo-controlled clinical trial, seventy active arthritis patients were allocated randomly into two groups who either received ginger powder or placebo daily for 12 weeks. Disease activity score and gene expression of immunity and inflammation intermediate factors were measured using quantitative real-time PCR before and after the intervention.
DAS-28= Disease Activity Score 
This clinical study is the first study to evaluate the effect of ginger on the expression of inflammation-related genes involved in immune system activity in arthritis patients. Previous studies have already shown that ginger has reduced pain and inflammation in patients with osteoarthritis and muscle discomfort , . Some human and animal studies have shown that anti-inflammatory effect of ginger is due to the inhibition of pro-inflammatory cytokines and chemokines production. For instance, in one clinical trial, supplementation with ginger extract daily for 12 weeks caused significant reduction in serum prostaglandin E2 (PGE2) and C-reactive protein (CRP), both of which are inflammatory proteins, compared with placebo . In support of these previous findings, the present study clearly shows that ginger extract can reduce arthritis manifestations and improve immune system function by decreasing inflammatory genes as factors involved in autoimmunity.
Platinum Turmeric Conclusion
Umbrella Supplements proprietary formulation of Platinum Turmeric with glucosamine, chondroitin, ginger and other supporting natural compounds offers unparalleled support for hip and joint disorders, using only the strongest, peer-reviewed evidence-based clinical data as a rationale for our synthesis, and leveraging our unparalleled Quality Control pipeline to validate the purity of each ingredient.
*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any diseases.
 C. Selvam et al., “Molecular mechanisms of curcumin and its analogs in colon cancer prevention and treatment,” Life Sciences, vol. 239. Elsevier Inc., 15-Dec-2019.
 Z. Ma, N. Wang, H. He, and X. Tang, “Pharmaceutical strategies of improving oral systemic bioavailability of curcumin for clinical application.,” J. Control. Release, vol. 316, pp. 359–380, Nov. 2019.
 D. M. Radomska-Leśniewska, A. Osiecka-Iwan, A. Hyc, A. Góźdź, A. M. Dąbrowska, and P. Skopiński, “Therapeutic potential of curcumin in eye diseases,” Cent. Eur. J. Immunol., vol. 44, no. 2, pp. 181–189, 2019.
 V. K. Singh, D. Arora, M. I. Ansari, and P. K. Sharma, “Phytochemicals based chemopreventive and chemotherapeutic strategies and modern technologies to overcome limitations for better clinical applications,” Phytotherapy Research. John Wiley and Sons Ltd, 2019.
 K. Mokbel, U. Wazir, and K. Mokbel, “Chemoprevention of prostate cancer by natural agents: Evidence from molecular and epidemiological studies,” Anticancer Research, vol. 39, no. 10. International Institute of Anticancer Research, pp. 5231–5259, 2019.
 A. Giordano and G. Tommonaro, “Curcumin and Cancer.,” Nutrients, vol. 11, no. 10, Oct. 2019.
 S. Shukla, D. Penta, P. Mondal, and S. M. Meeran, “Epigenetics of Breast Cancer: Clinical Status of Epi-drugs and Phytochemicals.,” Adv. Exp. Med. Biol., vol. 1152, pp. 293–310, 2019.
 N. Muniraj, S. Siddharth, and D. Sharma, “Bioactive compounds: Multi-targeting silver bullets for preventing and treating breast cancer,” Cancers, vol. 11, no. 10. MDPI AG, 01-Oct-2019.
 A. Golonko, H. Lewandowska, R. Świsłocka, U. T. Jasińska, W. Priebe, and W. Lewandowski, “Curcumin as tyrosine kinase inhibitor in cancer treatment,” European Journal of Medicinal Chemistry, vol. 181. Elsevier Masson SAS, 01-Nov-2019.
 H. Bashang and S. Tamma, “The use of curcumin as an effective adjuvant to cancer therapy: A short review.,” Biotechnol. Appl. Biochem., Oct. 2019.
 L. Avila-Carrasco et al., “Natural Plants Compounds as Modulators of Epithelial-to-Mesenchymal Transition,” Front. Pharmacol., vol. 10, Jul. 2019.
 M. D. Cas and R. Ghidoni, “Dietary curcumin: Correlation between bioavailability and health potential,” Nutrients, vol. 11, no. 9. MDPI AG, 01-Sep-2019.
 J. A. Flores-Pérez, F. de la Rosa Oliva, Y. Argenes, and A. Meneses-Garcia, “Nutrition, Cancer and Personalized Medicine.,” Adv. Exp. Med. Biol., vol. 1168, pp. 157–168, 2019.
 L. Vollono et al., “Potential of Curcumin in Skin Disorders.,” Nutrients, vol. 11, no. 9, 2019.
 I. Alwi et al., “The effect of curcumin on lipid level in patients with acute coronary syndrome.,” Acta Med. Indones., vol. 40, no. 4, pp. 201–210, 2008.
 M. Dastani et al., “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. phytomedicine, vol. 9, no. 1, pp. 1–9.
 S. C. Gupta, S. Patchva, W. Koh, and B. B. Aggarwal, “Discovery of curcumin, a component of golden spice, and its miraculous biological activities,” Clin. Exp. Pharmacol. Physiol., vol. 39, no. 3, pp. 283–299, Mar. 2012.
 W. Wongcharoen and A. Phrommintikul, “The protective role of curcumin in cardiovascular diseases,” International Journal of Cardiology, vol. 133, no. 2. pp. 145–151, 03-Apr-2009.
 N. Ghanaatian et al., “Curcumin as a therapeutic candidate for multiple sclerosis: Molecular mechanisms and targets,” Journal of Cellular Physiology, vol. 234, no. 8. Wiley-Liss Inc., pp. 12237–12248, 01-Aug-2019.
 M. Hatami, M. Abdolahi, N. Soveyd, M. Djalali, M. Togha, and N. M. Honarvar, “Molecular Mechanisms of Curcumin in Neuroinflammatory Disorders: A Mini Review of Current Evidences.,” Endocr. Metab. Immune Disord. Drug Targets, vol. 19, no. 3, pp. 247–258, 2019.
 R. Pluta, M. Ułamek-Kozioł, and S. J. Czuczwar, “Neuroprotective and neurological/cognitive enhancement effects of curcumin after brain ischemia injury with alzheimer’s disease phenotype,” International Journal of Molecular Sciences, vol. 19, no. 12. MDPI AG, 2018.
 S. Abrahams, W. L. Haylett, G. Johnson, J. A. Carr, and S. Bardien, “Antioxidant effects of curcumin in models of neurodegeneration, aging, oxidative and nitrosative stress: A review.,” Neuroscience, vol. 406, pp. 1–21, May 2019.
 E. Mhillaj, A. Tarozzi, L. Pruccoli, V. Cuomo, L. Trabace, and C. Mancuso, “Curcumin and Heme Oxygenase: Neuroprotection and Beyond.,” Int. J. Mol. Sci., vol. 20, no. 10, May 2019.
 P. Lorena, S. Tiziana, N. Filomena, T. Chiara, S. Simone, and M. Mariarosa Anna Beatrice, “The autophagy signaling pathway: A potential multifunctional therapeutic target of curcumin in neurological and neuromuscular diseases,” Nutrients, vol. 11, no. 8. MDPI AG, 01-Aug-2019.
 A. Popa-Wagner et al., “Dietary habits, lifestyle factors and neurodegenerative diseases,” Neural Regeneration Research, vol. 15, no. 3. Wolters Kluwer Medknow Publications, pp. 394–400, 01-Mar-2020.
 R. Vázquez-Fresno, A. R. R. Rosana, T. Sajed, T. Onookome-Okome, N. A. Wishart, and D. S. Wishart, “Herbs and Spices- Biomarkers of Intake Based on Human Intervention Studies - A Systematic Review.,” Genes Nutr., vol. 14, p. 18, 2019.
 H. Bagheri, F. Ghasemi, G. E. Barreto, R. Rafiee, T. Sathyapalan, and A. Sahebkar, “Effects of curcumin on mitochondria in neurodegenerative diseases,” BioFactors. Blackwell Publishing Inc., 2019.
 M. Concetta Scuto et al., “Curcumin, Hormesis and the Nervous System.,” Nutrients, vol. 11, no. 10, Oct. 2019.
 S. Dudics et al., “Natural products for the treatment of autoimmune arthritis: Their mechanisms of action, targeted delivery, and interplay with the host microbiome,” International Journal of Molecular Sciences, vol. 19, no. 9. MDPI AG, 01-Sep-2018.
 E. Asteriou, A. Gkoutzourelas, A. Mavropoulos, C. Katsiari, L. I. Sakkas, and D. P. Bogdanos, “Curcumin for the management of periodontitis and early ACPA-positive rheumatoid arthritis: Killing two birds with one stone,” Nutrients, vol. 10, no. 7. MDPI AG, 16-Jul-2018.
 M. Mantzorou, E. Pavlidou, G. Vasios, E. Tsagalioti, and C. Giaginis, “Effects of curcumin consumption on human chronic diseases: A narrative review of the most recent clinical data,” Phytotherapy Research, vol. 32, no. 6. John Wiley and Sons Ltd, pp. 957–975, 01-Jun-2018.
 P. Conigliaro et al., “Challenges in the treatment of Rheumatoid Arthritis.,” Autoimmun. Rev., vol. 18, no. 7, pp. 706–713, Jul. 2019.
 A. Attiq, J. Jalil, K. Husain, and W. Ahmad, “Raging the War Against Inflammation With Natural Products.,” Front. Pharmacol., vol. 9, p. 976, 2018.
 M. Yang, U. Akbar, and C. Mohan, “Curcumin in Autoimmune and Rheumatic Diseases.,” Nutrients, vol. 11, no. 5, May 2019.
 J. Langhorst et al., “Systematic Review of Complementary and Alternative Medicine Treatments in Inflammatory Bowel Diseases,” J. Crohn’s Colitis, vol. 9, no. 1, pp. 86–106, Jan. 2015.
 S. Bengmark, “Nutritio1. Bengmark S. Nutrition of the critically ill - emphasis on liver and pancreas. Hepatobiliary Surg Nutr. 2012;1(1):25-52. doi:10.3978/j.issn.2304-3881.2012.10.14.n of the critically ill - emphasis on liver and pancreas.,” Hepatobiliary Surg. Nutr., vol. 1, no. 1, pp. 25–52, 2012.
 A. Shehzad, M. Qureshi, M. N. Anwar, and Y. S. Lee, “Multifunctional Curcumin Mediate Multitherapeutic Effects.,” J. Food Sci., vol. 82, no. 9, pp. 2006–2015, Sep. 2017.
 A. Tarasiuk and J. Fichna, “Effectiveness and therapeutic value of phytochemicals in acute pancreatitis: A review.,” Pancreatology, vol. 19, no. 4, pp. 481–487, Jun. 2019.
 D. Akbik, M. Ghadiri, W. Chrzanowski, and R. Rohanizadeh, “Curcumin as a wound healing agent.,” Life Sci., vol. 116, no. 1, pp. 1–7, Oct. 2014.
 A. Sarkar, R. De, and A. K. Mukhopadhyay, “Curcumin as a potential therapeutic candidate for Helicobacter pylori associated diseases.,” World J. Gastroenterol., vol. 22, no. 9, pp. 2736–48, Mar. 2016.
 S. Kwiecien et al., “Curcumin: A Potent Protectant against Esophageal and Gastric Disorders.,” Int. J. Mol. Sci., vol. 20, no. 6, Mar. 2019.
 S. Ghosh, S. Banerjee, and P. C. Sil, “The beneficial role of curcumin on inflammation, diabetes and neurodegenerative disease: A recent update,” Food and Chemical Toxicology, vol. 83. Elsevier Ltd, pp. 111–124, 01-Sep-2015.
 Y. Rivera-Espinoza and P. Muriel, “Pharmacological actions of curcumin in liver diseases or damage.,” Liver Int., vol. 29, no. 10, pp. 1457–66, Nov. 2009.
 M. H. Farzaei et al., “Curcumin in Liver Diseases: A Systematic Review of the Cellular Mechanisms of Oxidative Stress and Clinical Perspective.,” Nutrients, vol. 10, no. 7, Jul. 2018.
 H. Khan, H. Ullah, and S. M. Nabavi, “Mechanistic insights of hepatoprotective effects of curcumin: Therapeutic updates and future prospects.,” Food Chem. Toxicol., vol. 124, pp. 182–191, Feb. 2019.
 P. Anand, A. B. Kunnumakkara, R. A. Newman, and B. B. Aggarwal, “Bioavailability of curcumin: Problems and promises,” Molecular Pharmaceutics, vol. 4, no. 6. pp. 807–818, Nov-2007.
 G. Shoba, D. Joy, T. Joseph, M. Majeed, R. Rajendran, and P. S. S. R. Srinivas, “Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers,” Planta Med., vol. 64, no. 4, pp. 353–356, 1998.
 A. S. A. Manap et al., “Synergistic effects of curcumin and piperine as potent acetylcholine and amyloidogenic inhibitors with significant neuroprotective activity in sh-sy5y cells via computational molecular modeling and in vitro assay,” Front. Aging Neurosci., vol. 10, no. JUL, 2019.
 S. C. Gupta, S. Patchva, and B. B. Aggarwal, “Therapeutic roles of curcumin: Lessons learned from clinical trials,” AAPS Journal, vol. 15, no. 1. pp. 195–218, Jan-2013.
 N. Dhillon et al., “Phase II trial of curcumin in patients with advanced pancreatic cancer,” Clin. Cancer Res., vol. 14, no. 14, pp. 4491–4499, Jul. 2008.
 M. Kanai et al., “A phase I/II study of gemcitabine-based chemotherapy plus curcumin for patients with gemcitabine-resistant pancreatic cancer,” Cancer Chemother. Pharmacol., vol. 68, no. 1, pp. 157–164, Jul. 2011.
 B. Chandran and A. Goel, “A Randomized, Pilot Study to Assess the Efficacy and Safety of Curcumin in Patients with Active Rheumatoid Arthritis,” Phyther. Res., vol. 26, no. 11, pp. 1719–1725, Nov. 2012.
 V. Kuptniratsaikul, S. Thanakhumtorn, P. Chinswangwatanakul, L. Wattanamongkonsil, and V. Thamlikitkul, “Efficacy and safety of Curcuma domestica extracts in patients with knee osteoarthritis,” J. Altern. Complement. Med., vol. 15, no. 8, pp. 891–897, Aug. 2009.
 S. Sharma, K. Chopra, and S. K. Kulkarni, “Effect of insulin and its combination with resveratrol or curcumin in attenuation of diabetic neuropathic pain: Participation of nitric oxide and TNF-alpha,” Phyther. Res., vol. 21, no. 3, pp. 278–283, Mar. 2007.
 S. Sharma, S. K. Kulkarni, J. N. Agrewala, and K. Chopra, “Curcumin attenuates thermal hyperalgesia in a diabetic mouse model of neuropathic pain,” Eur. J. Pharmacol., vol. 536, no. 3, pp. 256–261, May 2006.
 N. Mittal, R. Joshi, D. Hota, and A. Chakrabarti, “Evaluation of antihyperalgesic effect of curcumin on formalin-induced orofacial pain in rat,” Phyther. Res., vol. 23, no. 4, pp. 507–512, Apr. 2009.
 H. Tajik, E. Tamaddonfard, and N. Hamzeh-Gooshchi, “The effect of curcumin (active substance of turmeric) on the acetic acid-induced visceral nociception in rats,” Pakistan J. Biol. Sci., vol. 11, no. 2, pp. 312–314, 2008.
 H. Tajik, E. Tamaddonfard, and N. Hamzeh-Gooshchi, “Interaction between curcumin and opioid system in the formalin test of rats,” Pakistan J. Biol. Sci., vol. 10, no. 15, pp. 2583–2586, Aug. 2007.
 S. R. Rainey-Smith et al., “Curcumin and cognition: a randomised, placebo-controlled, double-blind study of community-dwelling older adults,” 2016.
 K. H. Cox, A. Pipingas, and A. B. Scholey, “Investigation of the effects of solid lipid curcumin on cognition and mood in a healthy older population,” J. Psychopharmacol., vol. 29, no. 5, pp. 642–651, May 2015.
 S. K. Kulkarni, M. K. Bhutani, and M. Bishnoi, “Antidepressant activity of curcumin: Involvement of serotonin and dopamine system,” Psychopharmacology (Berl)., vol. 201, no. 3, pp. 435–442, Dec. 2008.
 G. Pistone, A. D. Marino, C. Leotta, S. Dell’Arte, G. Finocchiaro, and M. Malaguarnera, “Levocarnitine administration in elderly subjects with rapid muscle fatigue: Effect on body composition, lipid profile and fatigue,” Drugs and Aging, vol. 20, no. 10, pp. 761–767, 2003.
 G. P. Eckert et al., “Curcumin prevents mitochondrial dysfunction in the brain of the senescence-accelerated mouse-prone 8,” Neurochem. Int., vol. 62, no. 5, pp. 595–602, Apr. 2013.
 H. Jiang et al., “Antidepressant-like effects of curcumin in chronic mild stress of rats: Involvement of its anti-inflammatory action,” Prog. Neuro-Psychopharmacology Biol. Psychiatry, vol. 47, pp. 33–39, Dec. 2013.
 M. K. Bhutani, M. Bishnoi, and S. K. Kulkarni, “Anti-depressant like effect of curcumin and its combination with piperine in unpredictable chronic stress-induced behavioral, biochemical and neurochemical changes,” Pharmacol. Biochem. Behav., vol. 92, no. 1, pp. 39–43, Mar. 2009.
 D. J. Leong, M. Choudhury, D. M. Hirsh, J. A. Hardin, N. J. Cobelli, and H. B. Sun, “Nutraceuticals: Potential for chondroprotection and molecular targeting of osteoarthritis,” Int. J. Mol. Sci., vol. 14, no. 11, pp. 23063–23085, Nov. 2013.
 O. D. Messina, M. Vidal Wilman, and L. F. Vidal Neira, “Nutrition, osteoarthritis and cartilage metabolism,” Aging Clinical and Experimental Research, vol. 31, no. 6. Springer International Publishing, pp. 807–813, 01-Jun-2019.
 J. Y. Reginster et al., “Long-term effects of glucosamine sulphate on osteoarthritis progression: A randomised, placebo-controlled clinical trial,” Lancet, vol. 357, no. 9252, pp. 251–256, Jan. 2001.
 M. C. Hochberg et al., “Combined chondroitin sulfate and glucosamine for painful knee osteoarthritis: A multicentre, randomised, double-blind, non-inferiority trial versus celecoxib,” Ann. Rheum. Dis., vol. 75, no. 1, pp. 37–44, Jan. 2016.
 V. Calamia et al., “Pharmacoproteomic study of the effects of chondroitin and glucosamine sulfate on human articular chondrocytes,” Arthritis Res. Ther., vol. 12, no. 4, Jul. 2010.
 M. W. Orth, T. L. Peters, and J. N. Hawkins, “Inhibition of articular cartilage degradation by glucosamine-HCl and chondroitin sulphate.,” Equine Vet. J. Suppl., no. 34, pp. 224–229, 2002.
 M. F. McCarty, A. L. Russell, and M. P. Seed, “Sulfated glycosaminsglycan and glucosamine may synergize in promoting synovial hyaluronic acid synthesis,” Med. Hypotheses, vol. 54, no. 5, pp. 798–802, 2000.
 L. Lippiello, J. Woodward, R. Karpman, and T. A. Hammad, “In vivo chondroprotection and metabolic synergy of glucosamine and chondroitin sulfate,” Clin. Orthop. Relat. Res., no. 381, pp. 229–240, 2000.
 C. Baigent et al., “Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: Meta-analyses of individual participant data from randomised trials,” Lancet, vol. 382, no. 9894, pp. 769–779, 2013.
 O. Journal, N. Aryaeian, and H. Tavakkoli, “ADVANCES IN FOOD TECHNOLOGY AND NUTRITIONAL SCIENCES Ginger and its Effects on Inflammatory Diseases Article History,” Adv Food Technol Nutr Sci Open J, vol. 1, no. 4, pp. 97–101, 2015.
 B. Ali, G. Blunden, M. Tanira, A. N.-F. and chemical Toxicology, and undefined 2008, “Some phytochemical, pharmacological and toxicological properties of ginger (Zingiber officinale Roscoe): a review of recent research,” Elsevier.
 N. Aryaeian, F. Shahram, M. Mahmoudi, H. Tavakoli, B. Yousefi, and T. Arablou, “The effect of ginger supplementation on some immunity and inflammation intermediate genes expression in patients with active Rheumatoid Arthritis,” Gene, vol. 698, pp. 179–185, May 2019.
 P. L. C. M. van Riel and J. Fransen, “DAS28: A useful instrument to monitor infliximab treatment in patients with rheumatoid arthritis,” Arthritis Res. Ther., vol. 7, no. 5, pp. 189–190, Oct. 2005.
 M. Haghighi, A. Khalvat, T. Toliat Phd, and S. Jallaei Msc, “COMPARING THE EFFECTS OF GINGER (ZINGIBER OFFICINALE) EXTRACT AND IBUPROFEN ON PATIENTS WITH OSTEOARTHRITIS,” 2005.
 R. D. Altman and K. C. Marcussen, “Effects of a ginger extract on knee pain in patients with osteoarthritis,” Arthritis Rheum., vol. 44, no. 11, pp. 2531–2538, 2001.
 T. Arablou, N. Aryaeian, M. Valizadeh, F. Sharifi, A. Hosseini, and M. Djalali, “The effect of ginger consumption on glycemic status, lipid profile and some inflammatory markers in patients with type 2 diabetes mellitus,” Int. J. Food Sci. Nutr., vol. 65, no. 4, pp. 515–520, 2014.