Presentazione del Dott. Andrea Piccozzi all'XI congresso Ortomed (Società Italiana di Ortopedia, Medicina e Malattie Rare dello Scheletro. Il dott. Piccozzi presenta i benefici derivanti dall'utilizzo della curcumina nelle sue forme bio-ottimizzate come la micellare nel trattamento del dolore cronico e dell'infiammazione nelle patologie osteoarticolai e non solo

1. «La Curcumina nel dolore cronico»
Dott. Andrea Piccozzi
Specialista in Medica Fisica e Riabilitazione
YAP researcher – Young Against Pain
Medico Sportivo
Team Doctor U.S. Triestina Calcio

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Chronic and degenerative illness
express high grade of inflammation
Cardiovascular diseases MSK pain
INFLAMMATION
Cancer
Auto-immune
diseases
Neuro degenerative
diseases
Type II diabetes High grade or Low grade

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Paradigm Shift in Inflammation

5. CGRP:Calcitonin gene related peptide; NMDA-R, N-methyl-D-aspartic acid receptor , EGF, epidermal growth factor; HIF, hypoxia
inducible factor; MMP, matrix metalloproteinase; PDGF, platelet-derived growth factor; TIMP, tissue inhibitor of metalloproteinase;
VEGF, vascular endothelial growth factor.
Iceberg Theory (2009, Fredberg et al.)

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Drugs used for pain management

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 Precautions in patients >70 years
 GI side effects
 Risks of gastic ulcers
 Attention in patients treated with
anti-coagulatns
 Risk of kidney impairment
Side effects and risks of NSAID’s
“Gli utilizzatori di FANS hanno
ulcere sintomatiche complicate 3-4
volte più frequentemente rispetto
ai non utilizzatori” 2
“Disturbi gastrici e intestinali
compaiono nel 10 - 30%
degli utilizzatori di FANS” 1
1-2Nederlandse Huisartsen Genootschap – pijnbestrijding: farmacotherapeutische richtlijn
3Cannon 2006, Chan 2006, Helin-Salmivaara 2006, Kearney 2006, McGettigan 2006

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 Curcuma longa
 Boswellia serrata
• Omega 3 (EPA and DHA)
 Zingiber officinale
Natural substances with anti-inflammatory activity

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• Rhizomatous, herbaceous,
perennial, plant
• Family Zingiberaceae
• Lives well with mild temperatures
(20°-30° C. and high rains
• Reach 1 m in hight
• Nice hermafrodite flowers in 20cm
inflorescence (August)
• Active sustances are concentrated
in rhizomes
Turmeric, the plant (Curcuma longa)

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Curcumin: THE active principle of turmeric
(1,7-bis (4-hydroxy-3-méthoxy-phényl) hepta-1,6-diène-3,5-dione)
Turmeric powder
contains 3-7% of Curcuminoids
essential oils and fibers

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8.770 studies shows pleiotroitropic effects
of curcumin (Pubmed)

12. Pubmed 18/11/2015
2367 publications
Curcumin anti-oxidant power is 10 time higher than Vit. E
- Direct activity on ROS
- Induction of NRF2
- Induce mitocondrial biogenesis
Curcumin is a powerful anti-oxidant

13. Epigenetic activity of Curcumin

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Epigenetic activity of curcumin
Molecular targets Activity Epigenetic and
anti-cancer
activity under
evaluation
DNA methylation,
HAT activities
Histone acetylation
(Acetil transferase/histone
deacetilase
HDAC isoenzymes (HDAC 1,3,4,5,8)
miRNA’s
miRNA’s target genes
Decrease
Decrease
Rebalance
Reduce
expression
Modulation
Regulation
Anti-oxidant,
anti-angiogenic,
antiproliferative
pro-apoptotic

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23
24
25
26
27
28
29
0
5
10
15
20
0
5
10
15
20
“Randomized, single blind study on efficacy and tolerability of
curcumin in patients with reumatoid poliarthritis “
Chandran et al. A Randomized, Pilot Study to Assess the Efficacy and Safety of Curcumin in Patients with Active Rheumatoid Arthritis. Phytother. Res. 2012;26:1719–
1725.
° n = 45 : curcumin n =15 ; diclofenac n = 15 ; curcumin and diclofenac n = 15
° 8 weeks , 1000 mg curcumin (BCM-95) e 100 mg diclofenac
Curcumin vs. NSAID’ (diclofenac )
Tassodisedimentazioneeritrocitaria(ESR)
- 11% - 8%
Significative reduction of
Disease Activity Score (DAS)
Significative reduction of
Joints pain
- 83%
- 69%
- 97% - 89%
Significative reduction of
Joints swelling
%Incidenza
%Incidenza
Curcumin
extract Diclofenac
1000 mg 100 mg
p < 0.05 p < 0.05 p < 0.05
Curcumin
extract Diclofenac
1000 mg 100 mg
Curcumin
extract Diclofenac
1000 mg 100 mg

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280
290
300
310
320
330
340
350
360
Ibuprofen Curcumina
° n = 367 : curcumin extract n = 182 ; ibuprofen n = 185
° After 4 weeks 1500 mg curcumin (2 capsuls 3x/die) e 1200 mg
ibuprofen (2 capsuls 3x/die).
° Simple turmeric extract
Mobility
Distance covered in 6 minutes
(Time 0 and after 4 weeks)
p = 0,010
Meterswalkedin6minutes
Chronic Pain
(Time 0 and after 4
weeks)
0
1
2
3
4
5
6
Ibuprofen Curcumina
p = 0,018
%Incidence
1200 mg 1500 mg 1200 mg 1500 mg
)
- 41%
+ 14% + 11%
Curcumin vs. NSAID’ (ibuprofen)
“Efficacy and safety of curcumin vs. Ibuprofen in patients
with knee arthrosis : a multicentric study“
Kuptniratsaikul V et al. Efficacy and safety of Curcuma domestica extracts compared with ibuprofen in patients with knee
osteoarthritis: a multicenter study. Clin Interv Aging. 2014 Mar 20;9:451-8.
- 39%

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Combination of Curcumin an ginger is effective as well as NSAID’S (indometacine)
Objective: measure effective of a blend of curcumin and ginger on pain
in patients with rheumatoid arthritis
3 groups NSAID’S (Indometacine) vs. 200 mg (CG) vs. 400 mg (CG)
Results:
Arthritic score
14d
Arthritic score
28d
Nsaid’s
(Indometacine)
 39.6%  50%
200 mg  41.7% 58.3%
400 mg  52.1%  78.6%
0
4
8
12
16
7 giorni 14 giorni 28 giorni
Controllo (dopo trattamento) Indometacina
200 mg curcumina +zenzero 400 mg curcumina+zenzero
- 78,6%- 52%Arthriticscore

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21. Curcuma polvere
Curcumina principio attivo (1)
Fitosoma (1)
Oli (1)
Ciclodestrina(1)
Forma micellare o Solubilizzata (2)
X 9,5 – 51,1
X 57,7
X 335
X 1350
X 7,3
Source:
• (1) Jäger et al, Nutrition Journal 2014, 13:11, comparative absorption of curcumin formulations.
• (2) Schiborr et al, Mol. Nutr. Food Res. 2014, 58, 516-527.
X 1
Biodisponibilità vs. Curcuma
Bioavailability of IMPROVED Curcumins

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• Curcuma longa is GRASS in the USA
Turmeric tolerability
• Curcumin is not carcinogenic
• No concerns of genotoxicity.
• ADI* of 3 mg/kg bw/day based on the NOAEL of 250-320
mg/kg bw/day
• Intake of curcumin from the normal diet amounts to less than
7% of the ADI of 3 mg/kg bw/day
• Possible weak interference with anti-coagulant that normally
do not require dosage adjustments.
*ADI = Accettable daily Intake

23. Curcumin as a background supplement in
MSK Pain Management
 In chronic msk pain:
50mg every 12 hours together with oppiods until
rehabilitation protocol is completed with improved
functionality for at least 3 months.
 In acute msk pain:
To dismiss /diminuish the use(abuse) of NSAIDs:
100mg in acute phase every 12 hours until pain
reduction.(NSAID continued until VAS<4/5)
Maintainance with 50mg every 12 hours until pain
relief.

26. Acute sports injuries:
2 softgel x 2 day for acute sport
injuries until full recovery
Chronic Muscle Soreness (DOMS):
1 x 2 softgel daily.
1 tablet: 50 mg curcumin (micellar)

27. Take home messages
Curcumin is effective on chronic pain and inflammation
as NSAID’s providing additional benefits (recovery)
«Enhanced » curcumins have better bioavailability
Curcumin is safe, can be used with all patients

28. Grazie per l’attenzione!