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«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
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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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-methoxy-phenyl) hepta-1,6-diene-3,5-dione)
Turmeric powder contains 3-7% of Curcuminoids essential oils and fibers
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
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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 )
Tass
o d
i sed
imen
tazi
on
e er
itro
cita
ria
(ESR
)
- 11% - 8%
Significative reduction of Disease Activity Score (DAS)
Significative reduction of Joints pain
- 83% - 69%
- 97% - 89%
Significative reduction of Joints swelling
% In
cid
enza
% In
cid
enza
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
Met
ers
wal
ked
in 6
min
ute
s
Chronic Pain (Time 0 and after 4
weeks)
0
1
2
3
4
5
6
Ibuprofen Curcuminap = 0,018
% In
cid
ence
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% A
rth
riti
c sc
ore
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
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.
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)
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