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Abstract

Turmeric, a spice that has long been recognized for its medicinal properties, has received interest from both the medical/scientific world and from culinary enthusiasts, as it is the major source of the polyphenol curcumin. It aids in the management of oxidative and inflammatory conditions, metabolic syndrome, arthritis, anxiety, and hyperlipidemia. It may also help in the management of exercise-induced inflammation and muscle soreness, thus enhancing recovery and performance in active people. In addition, a relatively low dose of the complex can provide health benefits for people that do not have diagnosed health conditions. Most of these benefits can be attributed to its antioxidant and anti-inflammatory effects. Ingesting curcumin by itself does not lead to the associated health benefits due to its poor bioavailability, which appears to be primarily due to poor absorption, rapid metabolism, and rapid elimination. There are several components that can increase bioavailability. For example, piperine is the major active component of black pepper and, when combined in a complex with curcumin, has been shown to increase bioavailability by 2000%. Curcumin combined with enhancing agents provides multiple health benefits. The purpose of this review is to provide a brief overview of the plethora of research regarding the health benefits of curcumin.
foods
Review
Curcumin: A Review of Its’ Effects on Human Health
Susan J. Hewlings 1, *ID and Douglas S. Kalman 2
1Department of Nutrition, Central Michigan University Mount Pleasant, MI, USA and Substantiation
Sciences Weston, FL 33143, USA
2Health and Human Performance, Nova Southeastern University and Nutrition Research Division, QPS,
Miami, FL 33143, USA; dougkalman@gmail.com
*Correspondence: sue.hewlings@gmail.com; Tel.: +1-321-377-4522
Received: 2 September 2017; Accepted: 20 October 2017; Published: 22 October 2017
Abstract:
Turmeric, a spice that has long been recognized for its medicinal properties, has received
interest from both the medical/scientific world and from culinary enthusiasts, as it is the major
source of the polyphenol curcumin. It aids in the management of oxidative and inflammatory
conditions, metabolic syndrome, arthritis, anxiety, and hyperlipidemia. It may also help in the
management of exercise-induced inflammation and muscle soreness, thus enhancing recovery and
performance in active people. In addition, a relatively low dose of the complex can provide health
benefits for people that do not have diagnosed health conditions. Most of these benefits can be
attributed to its antioxidant and anti-inflammatory effects. Ingesting curcumin by itself does not lead
to the associated health benefits due to its poor bioavailability, which appears to be primarily due
to poor absorption, rapid metabolism, and rapid elimination. There are several components that
can increase bioavailability. For example, piperine is the major active component of black pepper
and, when combined in a complex with curcumin, has been shown to increase bioavailability by
2000%. Curcumin combined with enhancing agents provides multiple health benefits. The purpose
of this review is to provide a brief overview of the plethora of research regarding the health benefits
of curcumin.
Keywords: curcumin; turmeric; antioxidant; anti-inflammatory; polyphenol
1. Introduction
Turmeric is a spice that has received much interest from both the medical/scientific worlds as
well as from the culinary world. Turmeric is a rhizomatous herbaceous perennial plant (Curcuma longa)
of the ginger family [
1
]. The medicinal properties of turmeric, the source of curcumin, have been
known for thousands of years; however, the ability to determine the exact mechanism(s) of action
and to determine the bioactive components have only recently been investigated [
2
]. Curcumin
(1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione), also called diferuloylmethane, is
the main natural polyphenol found in the rhizome of Curcuma longa (turmeric) and in others
Curcuma spp. [
3
]. Curcuma longa has been traditionally used in Asian countries as a medical herb
due to its antioxidant, anti-inflammatory [
4
], antimutagenic, antimicrobial [
5
,
6
], and anticancer
properties [7,8].
Curcumin, a polyphenol, has been shown to target multiple signaling molecules while also
demonstrating activity at the cellular level, which has helped to support its multiple health benefits [
2
].
It has been shown to benefit inflammatory conditions [
9
], metabolic syndrome [
10
], pain [
11
], and to
help in the management of inflammatory and degenerative eye conditions [
12
,
13
]. In addition, it has
been shown to benefit the kidneys [
14
]. While there appear to be countless therapeutic benefits to
curcumin supplementation, most of these benefits are due to its antioxidant and anti-inflammatory
effects [
2
,
9
]. Despite its reported benefits via inflammatory and antioxidant mechanisms, one of the
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Foods 2017,6, 92 2 of 11
major problems with ingesting curcumin by itself is its poor bioavailability [
15
], which appears to
be primarily due to poor absorption, rapid metabolism, and rapid elimination. Several agents have
been tested to improve curcumin’s bioavailability by addressing these various mechanisms. Most
of them have been developed to block the metabolic pathway of curcumin in order to increase its
bioavailability. For example, piperine, a known bioavailability enhancer, is the major active component
of black pepper [
16
] and is associated with an increase of 2000% in the bioavailability of curcumin [
17
].
Therefore, the issue of poor bioavailability appears to be resolved by adding agents such as piperine
that enhance bioavailability, thus creating a curcumin complex.
Curcumin is being recognized and used worldwide in many different forms for multiple potential
health benefits. For example, in India, turmeric—containing curcumin—has been used in curries; in
Japan, it is served in tea; in Thailand, it is used in cosmetics; in China, it is used as a colorant; in Korea, it
is served in drinks; in Malaysia, it is used as an antiseptic; in Pakistan, it is used as an anti-inflammatory
agent; and in the United States, it is used in mustard sauce, cheese, butter, and chips, as a preservative
and a coloring agent, in addition to capsules and powder forms. Curcumin is available in several
forms including capsules, tablets, ointments, energy drinks, soaps, and cosmetics [
2
]. Curcuminoids
have been approved by the US Food and Drug Administration (FDA) as “Generally Recognized As
Safe” (GRAS) [
2
], and good tolerability and safety profiles have been shown by clinical trials, even at
doses between 4000 and 8000 mg/day [
18
] and of doses up to 12,000 mg/day of 95% concentration of
three curcuminoids: curcumin, bisdemethoxycurcumin, and demethoxycurcumin [19].
It is the purpose of this review to provide a brief overview of the plethora of research regarding
the potential health benefits of curcumin. Due to the extent of the literature, we have chosen to focus on
the benefits associated with some common health conditions and on benefits in healthy people rather
than to review the extensive literature related to cancer and other disease states. For a comprehensive
review of curcumin’s effects on cancer, please see the paper by Kunnumakkara et al. 2017 [20].
2. Mechanisms of Action
2.1. Antioxidant
Antioxidant and anti-inflammatory properties are the two primary mechanisms that explain
the majority of the effects of curcumin on the various conditions discussed in this review [
21
,
22
].
Curcumin has been shown to improve systemic markers of oxidative stress [
23
]. There is evidence
that it can increase serum activities of antioxidants such as superoxide dismutase (SOD) [
24
26
].
A recent systematic review and meta-analysis of randomized control data related to the efficacy of
supplementation with purified curcuminoids on oxidative stress parameters—indicated a significant
effect of curcuminoids supplementation on all investigated parameters of oxidative stress including
plasma activities of SOD and catalase, as well as serum concentrations of glutathione peroxidase
(GSH) and lipid peroxides [
23
]. It is noteworthy to point out that all of the studies included in the
meta-analysis utilized some sort of formulation to overcome bioavailability challenges, and four
out of the six used piperine. Curcumin’s effect on free radicals is carried out by several different
mechanisms. It can scavenge different forms of free radicals, such as reactive oxygen and nitrogen
species (ROS and RNS, respectively) [
25
]; it can modulate the activity of GSH, catalase, and SOD
enzymes active in the neutralization of free radicals [
21
,
22
]; also, it can inhibit ROS-generating enzymes
such as lipoxygenase/cyclooxygenase and xanthine hydrogenase/oxidase [
21
]. In addition, curcumin
is a lipophilic compound, which makes it an efficient scavenger of peroxyl radicals, therefore, like
vitamin E, curcumin is also considered as a chain-breaking antioxidant [27].
2.2. Anti-Inflammatory
Oxidative stress has been implicated in many chronic diseases, and its pathological processes are
closely related to those of inflammation, in that one can be easily induced by another. In fact, it is known
that inflammatory cells liberate a number of reactive species at the site of inflammation leading to
Foods 2017,6, 92 3 of 11
oxidative stress, which demonstrates the relationship between oxidative stress and inflammation [
28
].
In addition, a number of reactive oxygen/nitrogen species can initiate an intracellular signaling cascade
that enhances pro-inflammatory gene expression. Inflammation has been identified in the development
of many chronic diseases and conditions [
10
,
19
,
29
,
30
]. These diseases include Alzheimer ’s disease
(AD), Parkinson’s disease, multiple sclerosis, epilepsy, cerebral injury, cardiovascular disease, metabolic
syndrome, cancer, allergy, asthma, bronchitis, colitis, arthritis, renal ischemia, psoriasis, diabetes,
obesity, depression, fatigue, and acquired immune deficiency syndromeAIDS [
10
]. Tumor necrosis
factor
α
(TNF-
α
) is a major mediator of inflammation in most diseases, and this effect is regulated by the
activation of a transcription factor, nuclear factor (NF)-
κ
B. Whereas TNF-
α
is said to be the most potent
NF-
κ
B activator, the expression of TNF-
α
is also regulated by NF-
κ
B. In addition to TNF-
α
, NF-
κ
B
is also activated by most inflammatory cytokines; gram-negative bacteria; various disease-causing
viruses; environmental pollutants; chemical, physical, mechanical, and psychological stress; high
glucose; fatty acids; ultraviolet radiation; cigarette smoke; and other disease-causing factors. Therefore,
agents that downregulate NF-
κ
B and NF-
κ
B–regulated gene products have potential efficacy against
several of these diseases. Curcumin has been shown to block NF-
κ
B activation increased by several
different inflammatory stimuli [
10
]. Curcumin has also been shown to suppress inflammation through
many different mechanisms beyond the scope of this review, thereby supporting its mechanism of
action as a potential anti-inflammatory agent [10].
3. Arthritis
One such disease associated with inflammation, both chronic and acute, is osteoarthritis (OA), a
chronic joint condition. It affects over 250 million people worldwide, leading to increased healthcare
costs, impairment in activities of daily living (ADL), and ultimately decreased quality of life [
31
,
32
].
Although OA was once considered primarily a degenerative and non-inflammatory condition, it
is now recognized as having inflammatory aspects, including elevated cytokine levels, as well as
potentially being connected with systemic inflammation [
33
,
34
]. While there is no cure, there are
several pharmaceutical options for treatment; however, many are costly and have undesirable side
effects. Therefore, there is increased interest in alternative treatments including dietary supplements
and herbal remedies [
35
]. Several studies have shown the anti-arthritic effects of curcumin in humans
with OA and rheumatoid arthritis (RA) [
36
39
]. In a randomized double-blind placebo-controlled
trial, 40 subjects with mild-to-moderate degree knee OA were randomly assigned to receive either
curcuminoid (500 mg/day in three divided doses; n= 19) with 5 mg piperine added to each 500-mg
dose or a matched placebo (n= 21) for six weeks. There were significantly greater reductions in the
visual analog scale (VAS) (p< 0.001), Western Ontario and McMaster Universities Osteoarthritis Index
(WOMAC) scores (p= 0.001), and Lequesne’s pain functional index (LPFI) (p= 0.013) scores in the
treatment group compared with the placebo group. When comparing the WOMAC subscales, there
were significant improvements in the pain and physical function scores (p< 0.001), but not in the
stiffness score [
40
]. There was also a decrease in systemic oxidative stress, as measured via serum
activities of SOD and concentrations of reduced GSH and malonedialdehyde (MDA), in subjects
receiving the treatment as compared to the placebo [
11
]. These improvements were not associated with
changes in circulating cytokines. The authors suggest that the lack of changes in circulating cytokines,
despite improvements in pain, may be because in OA, inflammatory markers in the synovial fluid may
be more likely elevated than systemic markers, whereas in RA, systemic markers may be more likely to
be increased. Therefore, they suggest that is more plausible that the beneficial effects of curcuminoids
in OA are because of local anti-inflammatory effects rather than systemic effects. In addition, the time
period of supplementation may not have been long enough. In a longer (eight months) randomized
control trial, 50 subjects diagnosed with OA were assigned to receive either standard treatment
as prescribed by their physician or standard treatment plus two 500-mg tablets daily consisting of
a natural curcuminoid mixture (20%), containing phosphatidyl-choline (40%) and microcrystalline
cellulose (40%). WOMAC, physical function, and stiffness scores decreased significantly (p< 0.05) in the
Foods 2017,6, 92 4 of 11
treatment group compared to the control. In addition, the treatment group showed significant decreases
in all markers of inflammation (soluble CD40 ligand(sCD40L), interleukin 1 beta (IL-1
β
), interleukin 6
(IL-6), soluble vascular cell adhesion molecule 1 (sVCAM-1), and erythrocyte sedimentation rate (ESR)
comparing baseline to follow-up, while the control group did not [
37
]. This study had both groups
maintaining standard care, which does not address the question of whether or not supplementation
with curcumin can be used instead of standard management such as nonsteroidal anti-inflammatory
drugs (NSAIDS). To address this question, 367 primary knee osteoarthritis patients with a pain score of
5 or higher were randomized to receive ibuprofen 1200 mg/day or C. domestica extracts 1500 mg/day
for four weeks. The mean of all WOMAC scores at weeks 0, 2, and 4 showed significant improvement
when compared with the baseline in both groups. After using the noninferiority test, the mean
difference (95% confidence interval) of WOMAC total, WOMAC pain, and WOMAC function scores at
week 4 adjusted by values at week 0 of C. domestica extracts were non-inferior to those for the ibuprofen
group (p= 0.010, p= 0.018, and p= 0.010, respectively), indicating that those taking the curcumin and
those taking the ibuprofen experienced the same benefits. The group taking the NSAIDS did experience
more gastrointestinal issues. This suggests that curcumin may offer an alternative to NSAIDS for
patients with OA seeking treatment but experiencing negative side effects [
12
]. This was supported by
results from a pilot study showing that a dose of 2 g of curcumin had an analgesic effect in subjects with
acute pain but without a diagnosis of OA. At this dose, the activity was higher than that associated
with 500 mg of acetaminophen, while a lower dose (1.5 g, 300 mg of curcumin) gave only transient
and often inadequate relief of pain, indicative of suboptimal therapeutic plasma concentrations. The
analgesic effect of the dose achieved significance only 2 h after administration, similar to that observed
for acetaminophen. In contrast, the NSAID was more rapidly acting, with the strongest pain relief
being reported one hour after administration but with significant gastrointestinalsymptoms. This
supports the use of 2 g (higher than needed for inflammation) curcumin for relief of pain as a potential
alternative to NSAIDS [41].
Regardless of the mechanism by which curcumin elicits its effects, it does appear to be beneficial
to several aspects of OA, as suggested by a recent systematic review and meta-analysis that concluded:
“This systematic review and meta-analysis provided scientific evidence that 8–12 weeks of standardized
turmeric extracts (typically 1000 mg/day of curcumin) treatment can reduce arthritis symptoms (mainly
pain and inflammation-related symptoms) and result in similar improvements in the symptoms as
ibuprofen and diclofenac sodium. Therefore, turmeric extracts and curcumin can be recommended for
alleviating the symptoms of arthritis, especially osteoarthritis” [42].
4. Metabolic Syndrome
The idea that curcumin can attenuate systemic inflammation has implications beyond arthritis,
as systemic inflammation has been associated with many conditions affecting many systems. One
such condition is Metabolic syndrome (MetS), which includes insulin resistance, hyperglycemia,
hypertension, low high-density lipoprotein cholesterol (HDL-C), elevated low-density lipoprotein
cholesterol (LDL-C), elevated triglyceride levels, and obesity, especially visceral obesity. Curcumin has
been shown to attenuate several aspects of MetS by improving insulin sensitivity [
43
,
44
], suppressing
adipogenesis [
45
], and reducing elevated blood pressure [
46
], inflammation [
47
], and oxidative
stress [
48
,
49
]. In addition, there is evidence that curcuminoids modulate the expression of genes
and the activity of enzymes involved in lipoprotein metabolism that lead to a reduction in plasma
triglycerides and cholesterol [
50
52
] and elevate HDL-C concentrations [
53
]. Both overweight and
obesity are linked to chronic low-grade inflammation; although the exact mechanisms are not
clear, it is known that pro-inflammatory cytokines are released. These cytokines are thought to
be at the core of the complications associated with diabetes and cardiovascular disease. Therefore,
addressing inflammation is important. In a randomized double-blind placebo-controlled trial with
a parallel-group design, 117 subjects with MetS received either 1 g curcumin plus 10 mg piperine
to increase absorption or a placebo plus 10 mg piperine for eight weeks. Within-group analysis
Foods 2017,6, 92 5 of 11
revealed significant reductions in serum concentrations of TNF-
α
, IL-6, transforming growth factor
beta (TGF-b), and monocyte chemoattractant protein-1 ( MCP-1) following curcumin supplementation
(p< 0.001). In the placebo group, serum levels of TGF-b were decreased (p= 0.003) but those of
IL-6 (p= 0.735), TNF-
α
(p= 0.138), and MCP-1 (p= 0.832) were not. Between-group comparison
suggested significantly greater reductions in serum concentrations of TNF-
α
, IL-6, TGF-b, and MCP-1
in the curcumin versus the placebo group (p< 0.001). Apart from IL-6, changes in other parameters
remained statistically significant after adjustment for potential confounders, including changes in
serum lipids and glucose levels, as well as the baseline serum concentration of the cytokines. The results
of this study suggest that curcumin supplementation significantly decreases serum concentrations
of pro-inflammatory cytokines in subjects with MetS [
11
]. In addition, the study looked at the
cholesterol-lowering properties and found that curcuminoids were more effective than the placebo
in reducing serum LDL-C, non-HDL-C, total cholesterol, triglycerides, and lipoprotein a (Lp(a)), in
addition to elevating HDL-C concentrations. However, changes in serum LDL-C levels were found to
be comparable between the study groups. The effects of curcuminoids on triglycerides, non-HDL-C,
total cholesterol, and Lp(a) remained significant after adjustment for baseline values of lipids and body
mass index [
54
]. From the same study, the authors also reported markers of oxidative stress. There
was a significant improvement in serum SOD activities (p< 0.001) and reduced MDA (p< 0.001) and
C-reactive protein (CRP) (p< 0.001) concentrations in the group receiving the curcumin with piperine
compared to the placebo group. Their secondary purpose was to perform a meta-analysis of data from
all randomized controlled trials in order to estimate the effect size of curcuminoids on plasma CRP
concentrations. Quantitative data synthesis revealed a significant effect of curcuminoids vs. placebo
in reducing circulating CRP concentrations The authors concluded that short-term supplementation
with a curcuminoid-piperine combination significantly improves oxidative and inflammatory status
in patients with MetS. Curcuminoids could therefore be regarded as natural, safe, and effective
CRP-lowering agents [55].
Inflammatory cytokines were also measured in the above study. Mean serum IL-1
β
(p= 0.042),
IL-4 (p= 0.008), and vascular endothelial growth factor (VEGF) (p= 0.01) were found to be significantly
reduced by curcumin therapy. In contrast, no significant difference was observed in the concentrations
of IL-2, IL-6, IL-8, IL-10, interferon gamma(IFN
γ
), epidermal growth factor (EGF), and MCP-1. The
authors suggest that the findings indicate that curcumin may exert immunomodulatory effects via
altering the circulating concentrations of IL-1β, IL-4, and VEGF [56].
In a randomized double-blind placebo-controlled crossover trial, 36 obese adults received either
1 g curcumin and 10 mg piperine or a placebo for 30 days followed by a two-week washout period, after
which they received the other treatment. A significant reduction in serum triglyceride concentrations
was observed, but the treatment did not have a significant influence on serum total cholesterol, LDL-C,
HDL-C, and high-sensitivity C-reactive protein (hs-CRP) concentrations, nor on body mass index
(BMI) and body fat. The authors suggest that the short supplemental period, lack of control of diet,
and the low supplemental dose may explain why these results conflict previous reports [50].
5. Healthy People
To date, the majority of curcumin studies in humans have been in populations with existing
health problems. Perhaps this is because studies on healthy people can be challenging in that benefits
may not be as immediate and measurable if biomarkers are normal at baseline. Therefore, following
subjects over time may provide the best insight into any potential health benefits in healthy people,
although such studies can be time-consuming and costly. Making cross-comparisons between the
few studies that have been done can be difficult because studies have used varying doses, often as
high as 1 g [
57
,
58
]. It should be noted that this would be considered a high dose only because it
is higher than what most people could obtain from consuming the spice itself [
49
]. One study on
healthy adults aged 40–60 years used an 80 mg/day dose of a lipidated form of curcumin. Subjects
were given either curcumin (N= 19) or a placebo (N= 19) for four weeks. The treatment was 400 mg
Foods 2017,6, 92 6 of 11
powder per day containing 80 mg curcumin. Blood and saliva were taken before and after the four
weeks. Curcumin significantly lowered triglyceride levels but not total cholesterol, LDL, or HDL levels.
There was a significant increase in nitrous oxide (NO) and in soluble intercellular adhesion molecule
1 (sICAM), a molecule linked to atherosclerosis. Inflammation-related neutrophil function increased,
as measured by myeloperoxidase concentration, but c-reactive protein and ceruloplasmin did not.
There was a decrease in salivary amylase activity, which can be a marker of stress, and an increase
in salivary radical scavenging capacities and plasma antioxidant enzyme catalase, but not in super
oxide dismutase or glutathione peroxidase. In addition, there was a decrease in beta amyloid plaque, a
marker of brain aging, and in plasma alanine amino transferase activities, a marker of liver injury. This
indicates that a relatively low dose of curcumin can provide health benefits for people that do not have
diagnosed health conditions [51].
In a randomized double-blind placebo-controlled trial, the acute (1 and 3 h after a single
dose), chronic (four weeks), and acute-on-chronic (1 and 3 h after single dose following chronic
treatment) effects of solid lipid curcumin formulation on cognitive function, mood, and blood
biomarkers in 60 healthy adults aged 60–85 years were examined. The curcumin formulation was
400 mg, approximately 80 mg curcumin in a solid lipid formulation with the remaining weight
comprised of commonly used pharmaceutical excipients and small amounts of other curcuminoids
present in turmeric extract. One hour after administration, curcumin significantly improved
performance on sustained attention and working memory tasks, compared with the 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 [59].
Another study examined whether supplementation with curcumin and Boswellia serrata (BSE)
gum resin for three months could affect plasma levels of markers of oxidative stress, inflammation, and
glycation in 47 male healthy master cyclists. All subjects were instructed to follow a Mediterranean
diet with 22 subjects receiving a placebo and 25 receiving 50 mg of turmeric, corresponding to 10 mg
of curcumin, as well as 140 mg of Boswellia extract, corresponding to 105 mg of Boswellia acid for
12 weeks. There was a positive effect observed on glycoxidation and lipid peroxidation in healthy
male master athletes [
60
]. This study indicates the potential for combining curcumin with other agents
to achieve health benefits.
Perhaps another challenge to interpreting studies on healthy people is determining the definition
of healthy, especially when considering that people who do not have an official diagnosis may still
participate in activities or experience situations whereby they challenge their daily physiological
homeostasis. For example, an exercise routine that one is not used to can cause inflammation, oxidative
challenges, and resulting soreness. In a recent study, 28 healthy subjects that did not participate
in resistance training were randomly assigned to receive either curcumin (400 mg/day) for two
days before and four days after participating in an eccentric exercise designed to induce muscle
soreness. Curcumin supplementation resulted in significantly smaller increases in creatine kinase (CK)
(
48%), TNF-
α
(
25%), and IL-8 (
21%) following exercise compared to the placebo. No significant
differences in IL-6, IL-10, or quadriceps muscle soreness between conditions were observed. The
findings demonstrated that the consumption of curcumin reduced biological inflammation, but not
subjective quadriceps muscle soreness during recovery from exercise. This may help to decrease
recovery time, thus improving performance during subsequent exercise sessions [61].
In a similar randomized placebo-controlled single-blind pilot trial, 20 male healthy, moderately
active volunteers were randomized to receive either 1 g curcumin twice daily (200 mg curcumin twice
a day ) or a placebo 48 h prior to and 24 h after a downhill running test. Subjects in the curcumin
group reported significantly less pain in the right and left anterior thigh. Significantly fewer subjects
in the curcumin group had MRI evidence of muscle injury in the posterior or medial compartment
of both thighs. Increases in markers of muscle damage and inflammation tended to be lower in the
Foods 2017,6, 92 7 of 11
curcumin group, but significant differences were only observed for interleukin-8 at 2 h after exercise.
No differences in markers of oxidative stress and muscle histology were observed. These results further
support that curcumin may be beneficial to attenuate exercise-induced muscle soreness (DOMS) [62].
A study by Delecroix et al. offers further support. They reported that 2 g of curcumin and 20 g of
piperine supplementation can help offset some of the physiological markers of muscle soreness after
an intense workout in elite rugby players [63].
In addition to acute physical stresses, humans may also suffer from periods of anxiety or
depression which are sub clinical, but may still benefit from treatments that can decrease the symptoms.
In a randomized double blind cross-over trial, 30 obese adults received curcuminoids (1 g/day) or
a placebo for 30 days, and then after a two-week washout period, crossed over to the alternate
regimen. The curcumin was a 500-mg C3 Complex
®
(standardized powder extract obtained from
Alleppey finger turmeric containing a minimum 95% concentration of three curcuminoids: curcumin,
bisdemethoxycurcumin, and demethoxycurcumin) plus 5 mg bioperine
®
per serving to enhance
absorption. Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI) scales were filled out
for each participant at baseline and after four, six, and 10 weeks of supplementation. Mean BAI score
was found to be significantly reduced following curcumin therapy (p= 0.03). However, curcumin
supplementation did not exert any significant impact on BDI scores. This study suggests that curcumin
has a potential anti-anxiety effect in otherwise healthy obese people [64].
6. Side Effects
Curcumin has a long established safety record. For example, according to JECFA (The Joint
United Nations and World Health Organization Expert Committee on Food Additives) and EFSA
(European Food Safety Authority) reports, the Allowable Daily Intake (ADI) value of curcumin is
0–3 mg/kg body weight [
65
]. Several trials on healthy subjects have supported the safety and efficacy
of curcumin. Despite this well-established safety, some negative side effects have been reported. Seven
subjects receiving 500–12,000 mg in a dose response study and followed for 72 h experienced diarrhea,
headache, rash, and yellow stool [
19
]. In another study, some subjects receiving 0.45 to 3.6 g/day
curcumin for one to four months reported nausea and diarrhea and an increase in serum alkaline
phosphatase and lactate dehydrogenase contents [66].
7. Conclusions
Curcumin has received worldwide attention for its multiple health benefits, which appear to act
primarily through its anti-oxidant and anti-inflammatory mechanisms. These benefits are best achieved
when curcumin is combined with agents such as piperine, which increase its bioavailability significantly.
Research suggests that curcumin can help in the management of oxidative and inflammatory conditions,
metabolic syndrome, arthritis, anxiety, and hyperlipidemia. It may also help in the management
of exercise-induced inflammation and muscle soreness, thus enhancing recovery and subsequent
performance in active people. In addition, a relatively low dose can provide health benefits for people
that do not have diagnosed health conditions.
Author Contributions:
Susan J. Hewlings and Douglas S. Kalman equally contributed to the background research,
writing, and reviewing of this manuscript.
Conflicts of Interest: The authors declare no conflict of interest.
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... Turmeric, from Curcuma longa, is a spice that is widely used in southern Asia, especially in India. Due to its beneficial therapeutic properties, it has been employed for years in traditional medicine [1] for wound healing, the treatment of respiratory conditions and liver and skin disorders, as well as for antimicrobial purposes. Moreover, many of its properties, such as its anti-inflammatory, anti-diabetic, anti-cancer, and anti-aging activities, have been described [1]. ...
... Due to its beneficial therapeutic properties, it has been employed for years in traditional medicine [1] for wound healing, the treatment of respiratory conditions and liver and skin disorders, as well as for antimicrobial purposes. Moreover, many of its properties, such as its anti-inflammatory, anti-diabetic, anti-cancer, and anti-aging activities, have been described [1]. Different bioactive compounds, including curcumin (diferuloylmethane, a natural polyphenol), desmethoxycurcumin, and bisdemethoxycurcumin are present in this spice [2]. ...
... Finally, nanocurcumin formulations were also effective in clinically improving the symptomatology of COVID-19 [21][22][23][24][25][26][27][28][29][30][31], although in patients it was difficult to determine whether the effects were related to the anti-inflammatory properties of curcumin [1] or to direct antiviral action [15][16][17][18][19]. ...
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Curcumin, the bioactive compound of the spice Curcuma longa, has already been reported as a potential COVID-19 adjuvant treatment due to its immunomodulatory and anti-inflammatory properties. In this study, SARS-CoV-2 was challenged with curcumin; moreover, curcumin was also coupled with laser light at 445 nm in a photodynamic therapy approach. Curcumin at a concentration of 10 μM, delivered to the virus prior to inoculation on cell culture, inhibited SARS-CoV-2 replication (reduction >99%) in Vero E6 cells, possibly due to disruption of the virion structure, as observed using the RNase protection assay. However, curcumin was not effective as a prophylactic treatment on already-infected Vero E6 cells. Notably, when curcumin was employed as a photosensitizer and blue laser light at 445 nm was delivered to a mix of curcumin/virus prior to the inoculation on the cells, virus inactivation was observed (>99%) using doses of curcumin that were not antiviral by themselves. Photodynamic therapy employing crude curcumin can be suggested as an antiviral option against SARS-CoV-2 infection.
... Curcumin is a bioactive polyphenol derived from the rhizome of the Curcuma longa-a turmeric plant. 5 Besides its therapeutic benets such as its antioxidant and anti-inammatory effects, 6 antimicrobial and anticarcinogenic activities, 7 curcumin is being combined to nanomaterials to design effective nanosensors for the detection of specic analytes. For example, liposomal curcumin nanocapsules in the presence of PDDA polymer were used to detect ATP molecule. ...
... 9 However, curcumin suffers from one major problem which is its poor bioavailability. 6 Also, other obstacles are associated with curcumin like low water solubility, crystalline nature and alkaline degradation. 10 Nevertheless, many methods had been studied to enhance the stability and the bioavailability of curcumin like the addition of agents like piperine, and the complexation in novel drug carriers such as liposomes, nanoparticles and micelles. ...
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The main purpose of this paper is to design curcumin loaded PLGA nanocapsules for the selective detection of dopamine using fluorescence spectroscopy.
... These results are consistent with previous research indicating the ability of curcumin to limit activation of osteoclasts via decreasing RANKL expression in bone marrow stromal cells and RAW264.7 cells (Oh et al., 2008;Park et al., 2011). Some evidence suggested that pro-inflammatory cytokines promoted the binding of RANKL to RANK, leading to the activation of osteoclastic signaling pathways and their differentiation and maturation (Kang et al., 2016;Yang et al., 2016;Yang et al., 2019); considering the anti-inflammatory properties of curcumin demonstrated in many research (Chainani-Wu 2003;Menon and Sudheer 2007;Ak and Gülçin 2008;Basnet and Skalko-Basnet 2011;Hewlings and Kalman 2017;Kadam et al., 2018;Safali et al., 2019), downregulation of these genes was in accordance with our expectations. OPG and RANKL are pivotal factors in the bone repair process and increased RANKL/OPG ratio was considered a marker of bone resorption (Chen et al., 2016). ...
Article
Objective: Following bone trauma, several factors participate in making a balance between the activity of osteoblasts and osteoclasts. The receptor activator of nuclear factor kappa B ligand (RANKL), receptor activator of nuclear factor kappa B (RANK), and osteoprotegerin (OPG) molecules play critical roles in the healing process via regulation of osteoclasts function. Turmeric is suggested to have an anti-osteogenic potential; however, its effect on accelerating bone healing has not been adequately studied. Here, we used a rat model of femur fracture to explore the effect of treatment with turmeric extract on the bone repair and the expression of RANK, RANKL, and OPG molecules. Materials and methods: Eight rats were subjected to surgery, randomly divided into two groups, and treated orally with turmeric (200 mg/kg), or olive oil. Four oil-treated rats without bone fracture were used as control group. After six weeks of treatment, the femurs of animals were examined for radiological, histological, and gene expression analysis. Results: X-ray radiography showed thicker callus and a more obscure fracture line in the turmeric group. Furthermore, higher osteoblast percentages but no osteoclasts were observed in turmeric-treated animals, representing better repair of bone in the fracture site. Also, real-time analyses showed that treatment with turmeric reduced RANK and RANKL expression (p<0.0001) and lowered RANKL/OPG ratio (p=0.01) in femoral bone tissue. Conclusion: Our findings indicated the turmeric ability to facilitate bone hemostasis and optimize the expression of key markers involved in the bone metabolism.
... Curcumin is a phenolic acid that also shows antitumor effects and alters the expression of Sp transcription factors. Sp transcription factors are members of the Sp/Krppellike family (KLF) conformed by Sp1, Sp2, Sp3, and Sp4 (Hewlings and Kalman, 2017). These Sp proteins are overexpressed in several tumors, including lung cancer. ...
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The acetylation status of histones located in both oncogenes and tumor suppressor genes modulate cancer hallmarks. In lung cancer, changes in the acetylation status are associated with increased cell proliferation, tumor growth, migration, invasion, and metastasis. Histone deacetylases (HDACs) are a group of enzymes that take part in the elimination of acetyl groups from histones. Thus, HDACs regulate the acetylation status of histones. Although several therapies are available to treat lung cancer, many of these fail because of the development of tumor resistance. One mechanism of tumor resistance is the aberrant expression of HDACs. Specific anti-cancer therapies modulate HDACs expression, resulting in chromatin remodeling and epigenetic modification of the expression of a variety of genes. Thus, HDACs are promising therapeutic targets to improve the response to anti-cancer treatments. Besides, natural compounds such as phytochemicals have potent antioxidant and chemopreventive activities. Some of these compounds modulate the deregulated activity of HDACs (e.g. curcumin, apigenin, EGCG, resveratrol, and quercetin). These phytochemicals have been shown to inhibit some of the cancer hallmarks through HDAC modulation. The present review discusses the epigenetic mechanisms by which HDACs contribute to carcinogenesis and resistance of lung cancer cells to anticancer therapies.
... Curcumin is a phytochemical and an active compound of turmeric (Curcuma longa L.) [13]. Evidence has shown some beneficial effects of curcumin on obesity, hypertension, dyslipidemia and glycemic control [14][15][16][17]. However, there is only one study (with limitations like short intervention duration) examining the effects of curcumin on the components of the MetS in subjects with MetS [18]. ...
Article
Full-text available
Background Metabolic syndrome (MetS) as a cluster of conditions including hyperlipidemia, hypertension, hyperglycemia, insulin resistance, and abdominal obesity is linked to cardiovascular diseases and type 2 diabetes. Evidence suggested that intake of curcumin and coenzyme Q10 may have therapeutic effects in the management of MetS. Aims We investigated the effects of curcumin and/or coenzyme Q10 supplementation on metabolic syndrome components including systolic blood pressure (SBP), diastolic blood pressure (DBP), waist circumference (WC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-c) and fasting plasma glucose (FPG) as primary outcomes, and total cholesterol (TC), low density lipoprotein-cholesterol (LDL-c) and body mass index (BMI) as secondary outcomes in subjects with MetS. Methods In this 2 × 2 factorial, randomized, double-blinded, placebo-controlled study, 88 subjects with MetS were randomly assigned into four groups including curcumin plus placebo (CP), or coenzyme Q10 plus placebo (QP), or curcumin plus coenzyme Q10 (CQ), or double placebo (DP) for 12 weeks. Results The CP group compared with the three other groups showed a significant reduction in HDL-c ( P = 0.001), TG ( P < 0.001), TC ( P < 0.001), and LDL-c ( P < 0.001). No significant differences were seen between the four groups in terms of SBP, DBP, FPG, WC, BMI and weight. Conclusion Curcumin improved dyslipidemia, but had no effect on body composition, hypertension and glycemic control. Furthermore, coenzyme Q10 as well as the combination of curcumin and coenzyme Q10 showed no therapeutic effects in subjects with MetS. The trial was registered on 09/21/2018 at the Iranian clinical trials website (IRCT20180201038585N2), URL: https://www.irct.ir/trial/32518 .
... It is also effective in treating symptoms associated with synovitis (knee pain), relief of synovial effusion or inflammation, and improving muscular knee strength. Curcumin's antioxidant and anti-inflammatory effects are effective in patients with osteoarthritis [11] . It has been shown to have similar efficacy to non-steroidal antiinflammatory drugs and glucosamine. ...
... Hepatoprotector is a drug compound that can provide protection to the liver from damage caused by drugs, chemical compounds, and viruses. One of the compounds that have been widely developed and used as a hepatoprotector is curcumin [10][11][12][13][14][15]. Curcumin, bis(4-hydroxy-3-methoxyphenyl)-1,6-diene-3,5-dione, which is also known as diferuloylmethane, is one of the lipophilic phenolic compounds in Curcuma domestica plant that is widely found in South Asia, India, Indochina, and other Asian countries, including Indonesia. ...
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Background and Aim: Developing curcumin into nanosized particles is one of the approaches to overcome the limited use of curcumin. This study aimed to prepare curcumin into nanosized particles to increase the curcumin level in the rat's liver and hepatoprotective effect in rats. Materials and Methods: Curcumin into nanosized particles formulated using ionic gelation method. Rats were divided into four groups (n = 6): Normal, negative, curcumin, and curcumin modified into nanosized particles were treated with 100 mg/ kg body weight orally for 14 days. Hepatic curcumin level was investigated using liquid chromatography with tandem mass spectrometry, antioxidant activity by malondialdehyde (MDA), and hepatoprotective effect by aspartate transaminase (AST), alanine transaminase (ALT), and histopathology. Results: The curcumin level in the rat's liver in the curcumin group was 12.19 ng/mL, and that in those receiving modified into nanosized curcumin was 209.36 ng/mL. The MDA levels in the normal, negative, curcumin, and curcumin modified into nanosized particles groups were 1.88, 4.87, 3.38, and 1.04 nmol/L, respectively. The AST levels in these groups were 57.12, 130.00, 102.13, and 74.28 IU/L, and the ALT levels were 21.63, 61.97, 39.38, and 28.55 IU/L. The liver histopathology scoring showed that curcumin in nanosized particles was better than curcumin in degeneration of fat, lymphocyte infiltration, and necrosis. Conclusion: There was a 17 times increase in curcumin level in the liver of rats treated with curcumin modified into nanosized particles. Curcumin modified into nanosized particles showed more significant improvement as antioxidant and hepatoprotector than curcumin.
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Curcumin, a polyphenol produced by turmeric (Curcuma longa), has attracted increased attention due to its potential as a novel cancer-fighting drug. However, to satisfy the required curcumin demand for health-related studies, high purity curcumin preparations are required, which are difficult to obtain and are very expensive. Curcumin and other curcuminoids are usually obtained through plant extraction. However, these polyphenols accumulate in low amounts over long periods in the plant and their extraction process is costly and not environmentally friendly. In addition, curcumin chemical synthesis is complex. All these reasons limit the advances in studies related to the in vitro and in vivo curcumin biological activities. The microbial production of curcumin appears as a solution to overcome the limitations associated with the currently used methods. Curcumin biosynthesis begins with the conversion of the aromatic amino acids, phenylalanine and tyrosine, into phenylpropanoids, the curcuminoid precursors. The phenylpropanoids are then activated through condensation with a CoA molecule. Afterwards, curcuminoids are synthesized by the action of type III polyketide synthases (PKS) that combine two activated phenylpropanoids and a malonyl-CoA molecule. To engineer microbes to produce curcumin, the curcuminoid biosynthetic genes must be introduced as microorganisms lack the enzymatic reactions responsible to synthesize curcuminoids. In this chapter, the advances regarding the microbial production of curcumin are exposed. The heterologous production of curcumin has been mainly achieved in the bacteria Escherichia coli. However, other microorganisms have already been explored. Besides the introduction of curcumin biosynthetic genes, the optimization of the microbial chassis must also be considered to maximize the production yields. The strategies employed for this purpose are also herein presented. The maximum titer of curcumin produced by a genetically engineered E. coli was 563.4 mg/L with a substrate conversion yield of 100% from supplemented ferulic acid. Moreover, the de novo production of curcumin was accomplished in E. coli reaching 3.8 mg/L of curcumin. Overall, the recent developments on curcumin heterologous production are very encouraging.
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Turmeric (Curcuma Longa) is a type of herb belonging to ginger family, which is widely grown in southern and south western tropical Asia region. Turmeric, which has an importance place in the cuisines of Iran, Malesia, India, China, Polynesia and Thailand, is often used as spice and has an effect on the nature, color and taste of foods. Turmeric is also known to have been used for centuries in India and China for the medical treatments of such illnesses as dermatologic diseases, infection, stress and depression. Turmeric's effects on health generally are centered upon an orange-yellow colored, lipophilic polyphenol substance called 'curcumin', which is acquired from the rhizomes of the herb. Curcumin is known recently to have antioxidant, anti-inflammatory, anti-cancer effects and, thanks to these effects, to have an important role in prevention and treatment of various illnesses ranging notably from cancer to autoimmune, neurological, cardiovascular diseases and diabetic. Furthermore, it is aimed to increase the biological activity and physiological effects of the curcumin on the body by synthesizing curcumin analogues. This paper reviews the history, chemical and physical features, analogues, metabolites, mechanisms of its physiological activities and effects on health of curcumin.
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Curcumin, a component of a spice native to India, was first isolated in 1815 by Vogel and Pelletier from the rhizomes of Curcuma longa (turmeric) and, subsequently, the chemical structure of curcumin as diferuloylmethane was reported by Milobedzka et al. [(1910) 43., 2163-2170].Since then, this polyphenol has been shown to exhibit antioxidant, anti-inflammatory, anticancer, antiviral, antibacterial, and antifungal activities. The current review primarily focuses on the anticancer potential of curcumin through the modulation of multiple cell signaling pathways. Curcumin modulates diverse transcription factors, inflammatory cytokines, enzymes, kinases, growth factors, receptors, and various other proteins with an affinity ranging from the pM to the mM range. Furthermore, curcumin effectively regulates tumor cell growth via modulation of numerous cell signaling pathways and potentiates the effect of chemotherapeutic agents and radiation against cancer. Curcumin can interact with most of the targets that are modulated by FDA-approved drugs for cancer therapy. The focus of this review is to discuss the molecular basis for the anticancer activities of curcumin based on preclinical and clinical findings.
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Background: Cytokines are involved in the development of metabolic abnormalities that may result in metabolic syndrome (MetS). Since curcumin has shown anti-inflammatory properties, the aim of this study was to evaluate the effect of curcumin supplementation on serum cytokines concentrations in subjects with MetS. Methods: This study was a post-hoc analysis of a randomized controlled trial in which males and females with diagnosis of MetS, according to the criteria defined by the National Cholesterol Education Program Adult Treatment Panel III guidelines, were studied. Subjects who met the inclusion criteria were randomly assigned to either curcumin (daily dose of 1g/day) or a matched placebo for a period of 8 weeks. Results: One hundred and seventeen subjects were assigned to either curcumin (n=59) or placebo (n=58) groups. Within-group analysis revealed significant reductions in serum concentrations of TNF-α, IL-6, TGF-β and MCP-1 following curcumin supplementation (p<0.001). In the placebo group, serum levels of TGF-β were decreased (p=0.003) but those of IL-6 (p=0.735), TNF-α (p=0.138) and MCP-1 (p=0.832) remained unaltered by the end of study. Between-group comparison suggested significantly greater reductions in serum concentrations of TNF-α, IL-6, TGF-β and MCP-1 in the curcumin versus placebo group (p<0.001). Apart from IL-6, changes in other parameters remained statistically significant after adjustment for potential confounders including changes in serum lipids and glucose levels, and baseline serum concentration of the cytokines. Conclusion: Results of the present study suggest that curcumin supplementation significantly decreases serum concentrations of pro-inflammatory cytokines in subjects with MetS.