«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

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-methoxy-phenyl) hepta-1,6-diene-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)

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

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 )

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

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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

Grazie per l’attenzione!