Diverse effects of a low dose supplement of lipidated curcumin in healthy middle aged people

Abstract

Background
Curcumin extracts of turmeric are proposed to produce health benefits. To date, human intervention studies have focused mainly on people with existing health problems given high doses of poorly absorbed curcumin. The purpose of the current study was to check whether in healthy people, a low dose of a lipidated curcumin extract could alter wellness-related measures.

Methods
The present study was conducted in healthy middle aged people (40–60 years old) with a low dose of curcumin (80 mg/day) in a lipidated form expected to have good absorption. Subjects were given either curcumin (N = 19) or placebo (N = 19) for 4 wk. Blood and saliva samples were taken before and after the 4 weeks and analyzed for a variety of blood and saliva measures relevant to health promotion.

Results
Curcumin, but not placebo, produced the following statistically significant changes: lowering of plasma triglyceride values, lowering of salivary amylase levels, raising of salivary radical scavenging capacities, raising of plasma catalase activities, lowering of plasma beta amyloid protein concentrations, lowering of plasma sICAM readings, increased plasma myeloperoxidase without increased c-reactive protein levels, increased plasma nitric oxide, and decreased plasma alanine amino transferase activities.

Conclusion
Collectively, these results demonstrate that a low dose of a curcumin-lipid preparation can produce a variety of potentially health promoting effects in healthy middle aged people.

Full text

R E S E A R C H Open Access
Diverse effects of a low dose supplement of
lipidated curcumin in healthy middle aged
people
Robert A DiSilvestro
*
, Elizabeth Joseph, Shi Zhao and Joshua Bomser
Abstract
Background: Curcumin extracts of turmeric are proposed to produce health benefits. To date, human intervention
studies have focused mainly on people with existing health problems given high doses of poorly absorbed
curcumin. The purpose of the current study was to check whether in healthy people, a low dose of a lipidated
curcumin extract could alter wellness-related measures.
Methods: The present study was conducted in healthy middle aged people (40–60 years old) with a low dose of
curcumin (80 mg/day) in a lipidated form expected to have good absorption. Subjects were given either curcumin
(N = 19) or placebo (N = 19) for 4 wk. Blood and saliva samples were taken before and after the 4 weeks and
analyzed for a variety of blood and saliva measures relevant to health promotion.
Results: Curcumin, but not placebo, produced the following statistically significant changes: lowering of plasma
triglyceride values, lowering of salivary amylase levels, raising of salivary radical scavenging capacities, raising of
plasma catalase activities, lowering of plasma beta amyloid protein concentrations, lowering of plasma sICAM
readings, increased plasma myeloperoxidase without increased c-reactive protein levels, increased plasma nitric
oxide, and decreased plasma alanine amino transferase activities.
Conclusion: Collectively, these results demonstrate that a low dose of a curcumin-lipid preparation can produce a
variety of potentially health promoting effects in healthy middle aged people.
Keywords: Curcumin, Catalase, Nitric oxide, Antioxidant capacity, Antioxidant activity
Background
Curcumin extracted from the spice turmeric shows many
different actions in cell cultures and experimental animals
[1-3]. However, the applicability of this work to human
health has been questioned due to the low absorption of
curcumin from extract supplement products [1,4-6]. Even
so, some studies of high doses of curcumin preparations
have had some effects in people with established health
problems rev in [1,2]. These doses are called high because
the 1 g or more quantities used in most studies exceed
what can be typically obtained by people using turmeric
related spices. At least one study has tried a much lower
dose of curcumin, but this study uses whole turmeric pro-
ducts that cannot really be called a concentrated curcumin
extract ie [7]. A few studies have also tried 500 mg curcu-
min/day as concentrated extract ie [8,9]. Yet, this dose is
still fairly high and has not always been given without an-
other active agent ie [9]. In the latter case, the effects of
the curcumin versus those of the other agent cannot easily
be distinguished. One exception to this high dose ap-
proach comes from a recent study that used 180 mg/day
of curcumin, but the curcumin by itself did not affect the
measures under consideration [10]. In contrast to these
studies, the present study examined a fairly concentrated
extract at 80 mg curcumin/day, which is a much lower
dose than has generally been tried in previous work. Also
in contrast to most previous work, the present study used
a lipid-curcumin mixture that was projected to be rela-
tively well absorbed.
Another difference between the present study and pre-
vious human work on curcumin is that the present study
* Correspondence: disilvestro.1@osu.edu
Department of Human Nutrition, The Ohio State University, 345 Campbell
Hall, 1787 Neil Ave, Columbus, OH 43210-1295, USA
© 2012 DiSilvestro et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the
Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use,
distribution, and reproduction in any medium, provided the original work is properly cited.
DiSilvestro et al. Nutrition Journal 2012, 11:79
http://www.nutritionj.com/content/11/1/79

examined healthy subjects rather than people with a
health problem. Nearly all of the previous human studies
on curcumin extracts have studied people with estab-
lished health problems. One exception is a study on
500 mg curcumin/day in relatively healthy people, but
the intervention lasted just 1 week [8]. More studies of
healthy people are needed because the curcumin effects
seen in cell cultures and experimental animals could re-
duce the risk of diseases not yet present.
In studies on cell cultures and experimental animals,
curcumin has shown a wide range of effects. For ex-
ample, curcumin has shown actions that affect lipid me-
tabolism [11-13] various anti-inflammatory pathways [3],
antioxidant reactions [1-3,14], endogenous antioxidant
levels [15-18], endogenous pro-oxidant molecule con-
centrations[3], neurological processes[19-21] and cardio-
vascular physiology [1,3]. Therefore, the present study
covered a wide range of potential mechanisms of action
for curcumin and a wide range of health implications.
Methods
Subjects
The protocol was approved by The Ohio State Univer-
sity Human Subjects Biomedical Institutional Review
Board. Apparently healthy adult males and post-
menopausal females, 40–60 years old, were recruited
from the Columbus, Ohio area. Potential subjects were
excluded for: current major health problems, cigarette
smoking, previous cardiovascular incidents, history of
cancer other than small sections of skin, regular use of
turmeric, dentist confirmed gingivitis, and use of supple-
mental phytochemical concentrates.
Research design
Accepted subjects were assigned to either starch placebo
or curcumin (N = 19/group, female/male split of 17/2,
mean age ± SEM of 48 ± 6 years for the placebo and
47 ± 5 years for the curcumin). The curcumin was Long-
vida
W
Optimized Curcumin from Curcuma Longa root
given at 400 mg powder per day containing 80 mg curcu-
min with each of the following ingredients as a propri-
etary blend: vegetable-derived stearic acid dextrin,
hydroxypropylmethylcellulose (vegetarian capsule), soy
lecithin, ascorbyl palmitate and silicon dioxide. Longvida
W
is a trademark of Verdure Sciences, Noblesville, IN, USA.
Subjects consumed the assigned product for 4 weeks,
with blood samples taken before and after the supple-
mentation period. Subjects were instructed to maintain
their previous dietary and exercise practices during
participation.
Laboratory analysis
After a fast of about 8 h or more, blood was collected
into a tube with heparin, centrifuged at 3000 x g for
30 min to obtain plasma and erythrocytes, and the ery-
throcytes were washed with phosphate buffered saline,
and then extracted with ethanol: chloroform as
described earlier [22]. Plasma was stored at −70°C and
the erythrocyte extract was stored at −20°C. Saliva was
obtained without acute stimulation and stored at −70°C
until assayed. Before assay, the saliva samples were
briefly centrifuged in an Eppendorf Microfuge to remove
solid material and precipitates.
Plasma total cholesterol, triglyceride, LDL, HDL and
alanine aminotransferase (ALT) were measured using
the Roche Cobas C111 Clinical Chemistry Analyzer (In-
dianapolis, Indiana, USA). Salivary amylase was deter-
mined using an ELISA kit from Salimetrics (State
College, Pennsylvania, USA). Plasma catalase and nitric
oxide were assayed using kits From Cayman Chemical
Company (Ann Arbor, Michigan, USA). Plasma βamyl-
oid protein (1–40) was measured with a commercial
ELISA kit from Wako Pure Chemical Industries (Osaka,
Japan). Plasma soluble intercellular adhesion molecule
(sICAM) was assayed by an ELISA kit from Invitrogen
(Frederick, Maryland, USA). Salivary antioxidant status
was assessed as free radical scavenging capacity by a kit
from Oxford Biomedical Research (Oxford, Michigan,
USA). Plasma c-reactive protein was determined by a
high sensitivity ELISA kit from MP Biomedicals (Solon,
Ohio, USA). Plasma myeloperoxidase was measured by
an ELISA kit from Assay Designs (Ann Arbor, Michigan,
USA). Plasma ceruloplasmin activity was determined
colorimetrically by oxidation of p-phenylenediamine as
described earlier [22]. Erythrocyte superoxide dismutase
was assayed by a spectrophotometric kinetic assay
described before [22].
Results
Curcumin supplementation produced a variety of effects
in plasma and saliva measures that are relevant to health
promotion. Supplementation, but not placebo, lowered
plasma triglyceride values (Figure 1). The curcumin ef-
fect did not extend to plasma lipids in general since no
significant effects were seen for plasma total cholesterol
(Figure 1) nor for LDL or HDL cholesterol (data not
shown).
Curcumin also affected two non-lipid related measures
relevant to cardiovascular health (Figure 2). One of these
effects was an increase in plasma contents of nitric
oxide, a molecule that can work against high blood pres-
sure [23]. The other cardiovascular-relevant effect was a
lowering of plasma concentrations of sICAM, a mol-
ecule linked to atherosclerosis [24].
Curcumin supplementation, but not placebo, raised
plasma myeloperoxidase concentrations (Figure 3), a
part of both normal and inflammation-related neutrophil
function [25,26]. This effect was not accompanied by a
DiSilvestro et al. Nutrition Journal 2012, 11:79 Page 2 of 8
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rise in plasma levels of c-reactive protein (Figure 3), nor
by a rise in ceruloplasmin values (data not shown), both
of which can be markers of inflammation [1,22,27]. In
addition, curcumin supplementation, but not placebo,
lowered salivary amylase activities (Figure 4), which
can mark sympathetic nervous system stress [28]. Cur-
cumin also raised salivary radical scavenging capacities
(Figure 4). The latter effect, a boosting of one
0
20
40
60
80
100
120
140
160
180
200
PrePlacebo PostPlacebo PreCurc PostCurc PrePlacebo PostPlacebo PreCurc PostCurc
TRIGLYCERIDES CHOLESTEROL
*
Figure 1 Curcumin effects on plasma triglycerides and cholesterol concentrations (mg/dl). Values are means ± SEM for N = 19 pre- and
post-treatment of 4 weeks. *Significantly different from pre-value, paired t-test, p < 0.05.
0
50
100
150
200
250
300
350
400
450
500
550
600
650
700
PrePlacebo PostPlacebo PreCurc PostCurc PrePlacebo PostPlacebo PreCurc PostCurc
NITRIC OXIDE sICAM
*
*
Figure 2 Curcumin effects on plasma concentrations of nitric oxide (μM x 10) and soluble intercellular adhesion molecule (sICAM)
(ng/ml). Values are means ± SEM for N = 19 pre- and post-treatment of 4 weeks. *Significantly different from pre-value, paired t-test, p < 0.05.
DiSilvestro et al. Nutrition Journal 2012, 11:79 Page 3 of 8
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determinant of antioxidant protection, was complimen-
ted by raising activities of the plasma antioxidant enzyme
catalase (Figure 5). However, this last effect did not
extend to all antioxidant enzymes as no effect was seen
for erythrocyte superoxide dismutase activities (Figure 5)
nor for plasma glutathione peroxidase (data not shown).
Curcumin supplementation, but not placebo, reduced
plasma contents of beta amyloid protein (Figure 6), a
0
5
10
15
20
25
30
PrePlacebo PostPlacebo PreCurc PostCurc PrePlacebo PostPlacebo PreCurc PostCurc
MYELOPEROXIDASE C-REACTIVE PROTEIN
*
Figure 3 Curcumin effects on plasma concentrations of myeloperoxidase (ng/ml) and c-reactive protein (mg/L x 10). Values are
means ± SEM for N = 19 pre- and post-treatment of 4 weeks. *Significantly different from pre-value, paired t-test, p < 0.05.
0
25
50
75
100
125
150
175
200
225
250
275
300
325
350
375
PrePlacebo PostPlacebo PreCurcumin PostCurcumin PrePlacebo PostPlacebo PreCurcumin PostCurcumin
AMYLASE ANTIOXIDANT STATUS
*
*
Figure 4 Curcumin effects on saliva activities of amylase (U/L) and antioxidant status (μM of copper reducing equivalents). Values are
means ± SEM for N = 19 pre- and post-treatment of 4 weeks. *Significantly different from pre-value, paired t-test, p < 0.05.
DiSilvestro et al. Nutrition Journal 2012, 11:79 Page 4 of 8
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maker of brain aging, especially in relation to Alzhei-
mer’s disease [29]. Curcumin also reduced plasma ala-
nine amino transferase activities (Figure 6), a liver injury
marker [30].
Discussion
This study demonstrated that in apparently healthy indi-
viduals, a relatively low dose of a specific curcumin
preparation can exert a variety of health promoting
0
10
20
30
40
50
60
PrePlacebo PostPlacebo PreCurc PostCurc PrePlacebo PostPlacebo PreCurc PostCurc
CATALASE SUPEROXIDE DISMUTASE
*
Figure 5 Curcumin effects on plasma activities of catalase (U/ml) and erythrocyte superoxide dismutase (U/ml packed cells x 10
-2
).
Values are means ± SEM for N = 19 pre- and post-treatment of 4 weeks. *Significantly different from pre-value, paired t-test, p < 0.01.
0
5
10
15
20
25
30
PrePlacebo PostPlacebo PreCurc PostCurc PrePlacebo PostPlacebo PreCurc PostCurc
ALT BETA AMYLOID PROTEIN
*
*
Figure 6 Curcumin effects on plasma activities of alanine aminotransferase (ALT) (U/L) and beta amyloid protein (pmoles/L). Values are
means ± SEM for N = 19 pre- and post-treatment of 4 weeks. *Significantly different from pre-value, paired t-test, p < 0.05.
DiSilvestro et al. Nutrition Journal 2012, 11:79 Page 5 of 8
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effects. Previous human intervention studies had gener-
ally emphasized much larger doses in people with exist-
ing health problems rev in [1,2,6]. Since the relatively
low dose used here did produce various bio-actions, pre-
sumably a good amount of curcumin was absorbed.
However, this was not tested directly. The variety of
actions seen here were tested for only one fairly narrow
age range, but future studies can examine other ages.
Certain dietary bioactive compounds only show very
distinct effects when counteracting a physiological stress.
This is likely why curcumin has been tested largely in
the presence of health problems in people and in animal
models for human disease. However, the wide variety of
potentially health promoting effects seen in the present
study suggests that curcumin can produce benefits in
people without immediate disease states. This diversity
of effects seen here conforms to the diverse range of
mechanisms that can be affected by curcumin in experi-
mental animals and cell cultures [1-3]. For example, cur-
cumin affected readings for both nitric oxide and
sICAM. Both of these molecules hold relevance for car-
diovascular disease risk, but from completely different
perspectives. Nitric oxide relates to blood pressure [23]
while sICAM relates to atherosclerosis [24]. The current
nitric oxide results may seem to contradict two previous
studies where curcumin reduces nitric oxide [31,32].
However, the previous studies examined inflammatory
states where nitric oxide levels can be raised by an indu-
cible synthesis enzyme. The curcumin effect seems to
result from actions on this enzyme [31], which would
not show much activity in the healthy, non-stressed sub-
jects studied here.
Another effect of curcumin was reduction of plasma
ALT activities, which are generally used to mark liver in-
jury [30]. This result for curcumin is consistent with
work in experimental animals with various chemically-
induced liver injuries ie [3,33]. In these animals, a rise in
ALT activities can be limited by administering curcumin.
However, two major differences exist between those
studies and the present work. First, the present study
utilized a much lower curcumin dose than in the animal
work, and second, the current study did not include any
overt chemical injury. Thus, the animal work raises the
possibility of using high dose curcumin for drug type
effects, but the current work raises the possibility of
using low dose curcumin for liver health maintenance.
This contrasts some suggestion that high dose curcumin
doses can produce liver toxicity [34].
In the present study, curcumin effects on blood lipids
gave mixed results compared to experimental animal
studies. Specifically, in the present study, curcumin low-
ered triglyceride readings but did not affect various types
of cholesterol readings. In experimental animals, curcu-
min can affect all these readings ie [11-14]. However, it
should be noted that these experimental animal models
induce high cholesterol and triglyceride levels via oral
intake of agents such as cholesterol, fat or alcohol. Con-
versely, in the present study, neither plasma cholesterol
nor triglycerides were elevated by any extreme dietary
intervention. Curcumin may regulate cholesterol
through mechanisms that only become major effectors
under certain stress conditions. In opposition to this
proposition, one study finds cholesterol lowering by
500 mg curcumin/day in relatively healthy people. How-
ever, this study lasted just 1 week [8]. In one other study
[35], curcumin failed to lower either cholesterol or tri-
glyceride readings. The exact dose given cannot be
ascertained since the percent curcumin of the extracts
were not analyzed. The study did provide evidence that
some curcumin was absorbed, but the amount absorbed
may not have been enough to lower triglyceride
readings.
Curcumin raised plasma myeloperoxidase, an effect
often associated with neutrophil mediated inflammation
[26]. Yet, in the present study, no change was seen for
either c-reactive protein or ceruloplasmin concentra-
tions, both of which rise with inflammation [22,27]. Pos-
sibly, the curcumin effect on myeloperoxidase indicated
strengthened cellular immune function, not an inflam-
matory reaction. Curcumin is known to strengthen some
aspects of cellular immunity even though it also sup-
presses pro-inflammatory aspects of immune function
[rev in 36].
Research in experimental animals and carried out
in vitro have raised the possibility that curcumin could
work against development of Alzheimer’s disease rev in
[21]. In the present study, curcumin decreased plasma
beta amyloid protein concentrations, which relates to
one mechanism by which curcumin may impact Alzhei-
mer’s disease development. Although the percent de-
crease was not big, the decrease could become larger
with a longer intervention.
In this study, curcumin showed signs of both direct
and indirect antioxidant actions. The curcumin-induced
increase in salivary radical scavenging capacity is consist-
ent with a direct antioxidant action (elimination of free
radicals by curcumin and/or its metabolites). Curcumin
has shown this type of activity in vitro [2,37]. In the
present study, curcumin also showed indirect antioxidant
action by elevating plasma activities of the endogenous
antioxidant enzyme catalase. Interestingly, low plasma
catalase is associated with a high risk for one form of car-
diovascular disease [38]. Experimental animal studies
provide precedent for curcumin stimulation of increases
in antioxidant enzyme activities [14-17]. In the present
study, plasma catalase activities increased after curcumin
treatment, but readings for two other antioxidant
enzymes, plasma glutathione peroxidase and erythrocyte
DiSilvestro et al. Nutrition Journal 2012, 11:79 Page 6 of 8
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superoxide dismutase, did not change. In contrast, curcu-
min is reported to increase all three enzymes in humans
exposed to arsenic [39]. However, this increase is not
from normal activities to above normal, which is what
was observed for catalase activities in the present study.
In the people with arsenic exposure, low activities are
partially returned to normal. Thus, the work with arsenic
exposed subjects pertains to protection against toxin-
induced reduction in activity, but the present study
considered activity elevations above normal for three
antioxidant enzymes. Although only the catalase activity
showed such elevation in blood samples, activities of the
other two antioxidant enzymes may have increased in
other body sites.
Conclusions
In summary, a low dose of a lipidated curcumin product
produced a range of potentially health promoting actions
in healthy middle aged people.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
RAD secured the funding, oversaw the study, and had the main writing
responsibility. EJ had the main responsibility for the laboratory analysis
including adapting methods to this study’s need. EJ also made some
decisions on the assay methodology to be used, formatted the paper, and
gave input on the study design and manuscript writing. SZ did some of the
laboratory work and made decisions on some of the assay methodology to
be used. SZ also gave input on the study design and manuscript writing. JB
was the lead investigator for human subject research regulation compliance
and contributed to study design and manuscript writing. All authors read
and approved the final manuscript.
Acknowledgements
This work was supported by a grant to RAD from Verdure Sciences. The
authors acknowledge Milena Micu for her assistance in contacting and
screening potential subjects.
Received: 24 July 2012 Accepted: 21 September 2012
Published: 26 September 2012
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Cite this article as: DiSilvestro et al.:Diverse effects of a low dose
supplement of lipidated curcumin in healthy middle aged people.
Nutrition Journal 2012 11:79.
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