Available via license: CC BY 4.0
Content may be subject to copyright.
Open Journal of Rheumatology and Autoimmune Diseases, 2013, 3, 104-107
http://dx.doi.org/10.4236/ojra.2013.32015 Published Online May 2013 (http://www.scirp.org/journal/ojra)
Flexofytol, a Purified Curcumin Extract, in Fibromyalgia
and Gout: A Retrospective Study*
Thierry Appelboom1, Christian Mélot MsciBiost2
1Rheumatology Department, Erasme University Hospital, Medical School, University of Brussels, Brussels, Belgium; 2Emergency
Department, Erasme University Hospital, Medical School, University of Brussels, Brussels, Belgium.
Email: thierry.appelboom@erasme.ulb.ac.be
Received February 26th, 2013; revised March 28th, 2013; accepted April 9th, 2013
Copyright © 2013 Thierry Appelboom, Christian Mélot MsciBiost. This is an open access article distributed under the Creative
Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original
work is properly cited.
ABSTRACT
Flexofytol is a recently-purified curcumin extract administered as a food supplement with the indication for being “able
to improve musculoskeletal flexibility and preserve articular function”. It is now marketed in Belgium, frequently used
with success in daily clinical practice according to pharmacists, and also prescribed by general practitioners and rheu-
matologists for various painful conditions. The objective of this retrospective study was to evaluate the potential effi-
cacy of the compound in fibromyalgia and gout from our practice from 2011-2012. Accordingly, the medical files of
116 patients (83 with a follow-up of 1 to 12 months) with fibromyalgia or gout who were treated with Flexofytol were
analysed to determine whether they had benefited from this therapy or had experienced undesirable effects. Flexofytol
provided a benefit in acute gout crisis and fibromyalgia. Interestingly, the clinical improvement was rapid (within 24 -
48 h), with good efficacy in gout. The benefit of Flexofytol was on different manifestations of pain rather than on the
sleep disorders of fibromyalgia. Except for some occasional difficulties with tablet swallowing and transient diarrhoea,
the treatment was well tolerated. In conclusion, Flexofytol appears to be an alternative to conventional treatment for
fibromyalgia and gout.
Keywords: Curcumin; Fibromyalgia; Gout
1. Introduction
Flexofytol is a recently purified curcumin extract licen-
sed and marketed by Tilman Laboratory (Belgium). Es-
sentially, it contains diferuloylmethane and 2 derived
compounds, demethoxycurcumin and bismethoxycurcu-
min. In order to facilitate intestinal absorption, the tablet
(42 mg) is supplemented with polysorbate as an emulsi-
fier, and citric acid as a pH stabilizer. Consequently, the
solubility of Flexofytol is 7500 times greater than that of
Curcuma.
The toxicity of Curcuma remains unknown, but dosa-
ges of 12 g daily have been administered for more than 3
months without side effects. A systematic review of cur-
cumin toxicity performed in 2003 concluded that there
was an absence of toxicity for dosages up to 8 g daily, and
that the compound has an anti-inflammatory effect. On the
other hand, Curcuma claims to exert protective effects on
the gastric mucosa, and to probably have a cicatrizing
effect on gastric ulcers (European Commission for Heal-
th). In traditional therapy, Curcuma is used in the treat-
ment of rheumatic pain and other clinical conditions in-
cluding Cancer, Helicobacter pylori infection, scabies
[1-4].
The ancient curry spice known as turmeric and its bioa-
ctive component, curcumin have been revered in the
world of Ayurvedic medicine for more than 2500 years.
Curcuma is thought to prevent digestive cancers, imp-
rove measures of cognition and brain health, including
Parkinson’s and Alzheimer’s, and to be a maintenance
therapy in ulcerative colitis [5,6].
Flexofytol has been marketed in Belgium since 2010
as a food additive for joint protection and improvement
of flexibility. The high number of Flexofytol tablets sold
in Belgium reflects a high degree of satisfaction among
patients. Now, Flexofytol is also prescribed by physi-
cians in daily practice, and improvement in diffuse pain,
lower back pain, tendonitis, and arthritis associated with
*Conflict of Interest: The authors received a financial support from
Tilman Laboratory (Belgium) for publishing their retrospective expe-
rience, the statistical analysis and the publication of the data.
Copyright © 2013 SciRes. OJRA
Flexofytol, a Purified Curcumin Extract, in Fibromyalgia and Gout: A Retrospective Study 105
Flexofytol is frequently reported. For these reasons, we
performed a retrospective analysis of our own experi-
ences, and assessed the tolerance of the compound from
our medical files of patients with fibromyalgia and gout.
2. Patients and Methods
Our population consisted of 116 patients treated during
the end of 2011 and the beginning of 2012 with Flexo-
fytol 4 tablets daily for fibromyalgia (n = 62) and gout (n
= 54), with a follow up visit after a period of 4 - 6 weeks
for 83 (42%) patients. The following information was re-
corded from the medical files: age, sex, and global assess-
ment of possible benefit. In fibromyalgia, additional infor-
mation generally available included the following ques-
tions: can you rate between 0 (no) and 10 (full) the seve-
rity of your symptoms (diffuse pain, fatigue, morning fati-
gue, abnormal fatigability, headache, dizziness, thoracic
oppression, muscle cramps, paraesthesia in the limbs,
intolerance to contact, noise, and odours), and the tender
points count. The presence of side effects was also recor-
ded.
Statistical Analysis
The data were presented as a histogram and as medians
with interquartile ranges (IQR) before and after treatment.
The medians were compared using a nonparametric test
for repeated measures (Wilcoxon signed rank test). The
percentage of responses before and after treatment was
compared using z-test. A p-value < 0.05 was considered
significant.
3. Results
3.1. Effect of Flexofytol in Fibromyalgia
Among the 62 patients treated with Flexofytol 4 tablets
daily, 41 felt that the therapy was beneficial. In the clini-
cal setting of fibromyalgia, diffuse pain and fatigue are
central. Therefore, it seemed interesting to look for an
effect on these symptoms in particular. Indeed, Flexo-
fytol reduced diffuse pain intensity, with the median
(IQR) shifting from 8 (7 - 8) to 6 (5 - 8) (p = 0.003)
(Figure 1). A benefit was also observed on fatigue; the
median (IQR) indicates a reduction from 8 (6 - 8) to 7 (5
- 8) (p = 0.0392) (Figure 2). Concerning morning fatigue,
which is often reported by these patients, the difference
was not significant (p = 0.0625) despite a reduction in the
median from 8 (7 - 8) to 6.5 (3.75 - 9). On the other hand,
fatigue during domestic work improved with a reduction
in median (IQR) from 8 (5 - 9) to 7.5 (5.25 - 8) (p =
0.0143).
Among the other symptoms of fibromyalgia, an impor-
tant reduction in dizziness was noted, with a median
(IQR) reduction from 5 (2 - 8) to 3 (1 - 7) (p = 0.0258),
as well as in thoracic oppression with a median decrease
0
5
10
15
20
25
Score
01 2 3 4 5 6 7 8 9 10
N = 58
000113
7
10
24
66
Number of patients
0
1
2
3
4
5
6
7
8
Score
01 2 3 4 5 6 7 8 9 10
N = 35
0
11
22
33
6
8
8
1
Median (IQR): from 8 (7 –8) to 6 (5 – 8), p = 0.0003
Number of patients
Fibromyalgia: pain
Before treatment After treatment
Figure 1. Fibromyalgia: effect of Flexofytol on pain (p =
0.0003).
0
5
10
15
20
25
Score
0 1 2 3 4 5 6 7 8 9 10
N = 58
02
00 1
75
10
23
55
Number of patients
Fibromyalgia: fatigue
0
1
2
3
4
5
6
7
8
9
Score
01 2 3 4 5 6 7 8 9 10
N = 32
0
1111
3
5
8
9
2
1
Median (IQR): from 8 (6 – 8) to 7 (5 – 8), p = 0.0392
Number of patients
Before treatment After treatment
Figure 2. Fibromyalgia: effect of Flexofytol on fatigue (p =
0.0392).
from 7 (6 - 8) to 5 (2.5 - 7) (p = 0.0015), heart palpita-
tions with a median reduction from 6 (3.75 - 8) to 5 (2 - 6)
(p = 0.004), cramps from 6 (4 - 8) to 4.5 (2 - 7) (p =
0.0096), and paraesthesia in the extremities from 7 (4 - 8)
to 4 (1 - 7) (p = 0.0018).
On the other hand, no significant benefit was observed
for headache, which remained unchanged from 6.5 (3 - 8)
to 6.5 (2 - 8)(p = 0.1477), perception of painful skin con-
tact from 8 (6 - 8) to 7 (5 - 8) (p = 0.3343), intolerance to
noise from 7 (4.75 - 8.25) to 7.5 (5-8) (p = 0.4412), or to
odours from 6 (0 - 8) to 5 (0 - 7) (p = 0.025). Tender
points, which are cardinal for the diagnosis of fibromyal-
gia and represent diagnostic criteria, were not modified
by treatment, with medians (IQR) ranging from 18 (18 -
18) to 18 (8 - 18) (p = 0.1814).
3.2. Effect of Flexofytol in Gout
With Flexofytol, 17/19 gout patients reported dramatic
Copyright © 2013 SciRes. OJRA
Flexofytol, a Purified Curcumin Extract, in Fibromyalgia and Gout: A Retrospective Study
106
improvements in acute gout symptoms within 24 - 48 h
with 4-6 Flexofytol tablets daily (p = 0.0002) (Figure 3).
Eleven patients decided to spontaneously continue the-
rapy to prevent recurrence by taking 2 tablets daily for 3
- 6 months, and 10/11 were satisfied after 6 months.
3.3. Undesirable Effects
Some patients reported difficulties swallowing the tablets
(n = 4/83), slight diarrhoea (n = 5/83), and skin itchiness
(n = 1/83) that spontaneously resolved when the dosage
was reduced from 4 to 2 tablets daily. When blood tes-
ting could be obtained (51/83), no alteration in renal,
liver, or hematopoietic function was noted.
3.4. Drug Interaction
Our experience is limited, but so far no drug interaction
was reported with warfarin (n = 2) or antidiabetic agents
(n = 4).
4. Discussion
The most benefit seen with Flexofytol was observed in
gout, with a majority of patients (17/19) reporting that
they experienced clinical improvement within 24 - 48 h,
which was similar to that obtained with non-steroidal
anti-inflammatory drugs (NSAIDs). It is important to
note that some patients decided to take 6 tablets daily
rather than 4 because they considered that a benefit was
present, but insufficient with the regular dose. Since this
first experience, 20/23 additional patients (not included
in this study) reported a benefit from Flexofytol, and con-
firmed excellent pain relief within 1 or 2 days. The same
group decided spontaneously to adopt Flexofytol as main-
tenance therapy because they felt that it provided a prote-
ctive effect against the recurrence of gout crisis (data not
shown).
In patients with fibromyalgia, a high proportion of pa-
0
2
4
6
8
10
12
14
16
18 17
Yes No
2
N = 19 p = 0.0002
Gout: pain improvement
Number of patients
Figure 3. Gout: number of patients improved (p = 0.0002).
tients reported experiencing clinical improvement. Intere-
stingly, some symptoms were more improved than others.
In decreasing order, paraesthesia, diffuse pain, dizziness,
muscle cramps, thoracic oppression, palpitations, and
intolerance to odours were improved. Fatigue and abnor-
mal fatigability for domestic work were not improved by
Flexofytol, and no benefit was observed for headache, in-
tolerance to contact or noise, or the number of tender
points.
Flexofytol was well tolerated. Two patients complai-
ned that the relatively large size of the tablet made swal-
lowing difficult, and 2 reported some laxative effects
when the dose was increased to 6 tablets daily for more
than 10 days.
This retrospective observational study provides only a
limited level of evidence. Accordingly, no definitive con-
clusion can be drawn, but these encouraging results sug-
gest further research and development of curcumin not
only as a food additive, but as a new drug. The main ad-
vantage of curcumin is its extensive use as a therapeutic
agent and as a cooking additive. No adverse events are
reported in the literature, even for high dosages. Conse-
quently, at first glance the compound could be indicated
for older, polymedicated, anticoagulated, or frail patients,
or in those with hepatic or renal alterations.
The good results in gout patients can be explained by
the particular mode of action of curcumin. In vitro, cur-
cumin can block production of IL-12 by CD4, CD8, and
NK cells, and, consequently, by the production of gamma
interferon [7] In addition, curcumin blocks the expres-
sion of IL-6 and IL-8 by chondrocytes [8]; it can also
stimulate the production of IL-4 and, consequently, in-
hibit the NF-kappa-B pathway implicated in the produ-
ction of cytokines.
Other in vitro studies have suggested that the com-
pound could inhibit enzymes involved in inflammation
such as phospholipase, cycloxygenase-2, and lipoxyge-
nase, NO production induced by interleukin-1 beta [8,9]
and the activity of enzymes like collagenase, elastase,
and hyaluronidase [10]; and to trap free radicals, supero-
xide anions, and some pro-inflammatory metals such as
iron and copper [11] Curcumin regulates transcription fac-
tors, kinases, adhesion molecules, redox status, and other
enzymes involved in inflammation [12].
These in vitro effects are relevant if curcumin can
penetrate the intestinal barrier and arrive at the site of
inflammation. Penetration of curcumin is highly variable
(5% - 60%) from one person to another. The main advan-
tage of Flexofytol is its physical transformation into mi-
cellae and its chemical design for penetration. This should
allow it to achieve high concentrations in the circulation
and in peripheral tissues. This penetration characteristic
differentiates Flexofytol from its competitors, which are
supplemented by piperidine (a pepper extract) or cyclo-
Copyright © 2013 SciRes. OJRA
Flexofytol, a Purified Curcumin Extract, in Fibromyalgia and Gout: A Retrospective Study
Copyright © 2013 SciRes. OJRA
107
dextrin, which represent alternatives for facilitating the
penetration of curcuma.
Other studies have also suggested an anti-inflamma-
tory role for curcumin since it reduces morning stiffness
in rheumatoid arthritis with an effect comparable to
NSAIDs. It could also induce partial relief from postope-
rative pain.
A positive effect was also reported in fibromyalgia pa-
tients. An important proportion (42%) of these patients
was lost to follow up, and whether they were satisfied or
dissatisfied with the treatment is unknown. If a placebo
effect is likely, it is balanced by the high number of fib-
romyalgia patients who are depressed, rarely express sa-
tisfaction with therapy, or do not comply with the treat-
ment plan.
The mode of action of Flexofytol in fibromyalgia is
difficult to explain. Interestingly, improvement was noted
in decreasing order for paraesthesia, diffuse pain, dizzi-
ness, cramps, thoracic oppression, palpitations, and less
significantly for fatigue during effort. No effect on heada-
che, intolerance to contact, noise, or on the number of
tender points was recorded.
Under these conditions, Flexofytol would play a role
in reducing pain rather than affecting sleep. As a hy-
pothesis, the target of Flexofytol could be the grey nuclei
of the brain, which play a more central role in pain con-
trol than the limbic system, which is active in sleep con-
trol.
In conclusion, in this retrospective, real-life study in
patients with gout and fibromyalgia, Flexofytol provided
a benefit without adverse effects. These results need to
be confirmed, and double-blind trials are necessary prior
to drawing any definitive conclusion. Yet, if confirmed,
Flexofytol could represent a safe and efficacious alterna-
tive treatment in these conditions.
REFERENCES
[1] C. Koosiriatt, S Linpisarn, D. Changsom, K. Chawansun-
tati and J. Wipasa, “Investigation of the Anti-Inflamma-
tory Effect of Curcuma in Helicobacter Pylori Infected
Patients,” International Immunopharmacology, Vol. 10,
No. 7, 2010, pp. 815-817.
doi:10.1016/j.intimp.2010.04.021
[2] B. Chandran and A. Goel, “A Randomized Pilot Study to
Assess the Efficacy and the Safety of Curcumin in Pa-
tients with Active Rheumatoid Arthritis,” Phytotherapy
Research, Vol. 26, No. 11, 2012, pp. 1719-1725.
doi:10.1002/ptr.4639
[3] A. S. Strimpakos and R. A. Sharma, “Curcumin: Preven-
tive and Therapeutic Properties in Laboratory Studies and
Clinical Trials,” Antioxidants & Redox Signaling, Vol. 10,
No. 3, 2008, pp. 511-545. doi:10.1089/ars.2007.1769
[4] T. Kawamori, R. Lubet, V. Steele, et al., “Chemopre-
ventive Effect of Curcumin a Naturally Occurring Anti-
Inflammatory Agent during the Promotion/Progression
Stages of Colon Cancer,” Cancer Research, Vol. 59, No.
3, 1999, pp. 597-601.
[5] T. Jida, K. Takeuchi, F. Watanabe, et al., “Curcumin
Maintenance Therapy for Ulcerative Colitis: Randomized,
Multicenter, Double-Blind, Placebo-Controlled Trial,”
Clinical Gastroenterology and Hepatology, Vol. 4, No. 2,
2006, pp. 1502-1506. doi:10.1016/j.cgh.2006.08.008
[6] T. Hamaguchi, K. Ono and M. Yamada, “Review: Cur-
cumin and Alzheimer’s Disease,” CNS and Neurosciences
and Therapeutics, Vol. 16, No. 5, 2010, pp. 285-297.
doi:10.1111/j.1755-5949.2010.00147.x
[7] B. Y. Kang, Y. J. Song, K. M. Kim, Y. K. Choe, S. Y.
Hwang and T. S. Kim, “Curcumin Inhibits Th1 Cytokine
Profile in CD4+ T Cells by Suppressing IL-12 Production
in Macrophages,” British Journal of Pharmacology, Vol.
128, No. 2, 1999, pp. 380-384.
doi:10.1038/sj.bjp.0702803
[8] M. Mathy, I. Jacquemond-Collet, F. Priem, C. Sanchez, C.
Lambert and Y. Henrotin, “Curcumin Inhibits Proinflam-
matory Mediators and Metalloproteinase-3 Production by
Chondrocytes,” Inflammation Research, Vol. 58, No. 12,
2009, pp. 899-908. doi:10.1007/s00011-009-0063-1
[9] V. P. Menon and A. R. Sudheer, “Antioxidant and Anti-
Inflammatory Properties of Curcumin,” Advances in Ex-
perimental Medicine and Biology, Vol. 595, 2007, pp.
105-125. doi:10.1007/978-0-387-46401-5_3
[10] N. Chainani-Wu, “Safety and Anti-Inflammatory Activity
of Curcumin a Component of Tumerin (Curcuma longa),”
The Journal of Alternative and Complementary Medicine,
2003 Vol. 9, No. 1, 2003, pp. 161-168.
doi:10.1089/107555303321223035
[11] H. Hatcher, R. Planalp, J. Cho, F. Torti and S. V. Torti,
“Curcumin: From Ancient Medicine to Current Clinical
Trials,” Cellular and Molecular Life Sciences, Vol. 65,
No. 11, 2008, pp. 1631-1652.
doi:10.1007/s00018-008-7452-4
[12] B. B. Aggarwal and K. B. Harikumar, “Potential Ther-
apeutic Effects of Curcumin, the Anti-Inflammatory Agent,
against Neurodegenerative, Cardiovascular, Pulmonary,
Metabolic, Autoimmune and Neoplastic Diseases,” The
International Journal of Biochemistry & Cell Biology,
Vol. 41, No. 1, 2009, pp. 40-59.
doi:10.1016/j.biocel.2008.06.010
