vitamin d and pain
TRANSCRIPT
Vitamin D and Pain
Vitamin D and Pain
Summary:1. Vit. D discovery 2. Metabolism and transformation to the active form3. A.R. (Daily allowance)4. Mechanism of actions5. Epigenetics6. Vit D and pain7. Supplementation and treatment of deficiences8. Safety profile of colechalciferol as source of Vit.D9. Sinergistic activity with other natural bioactive substances
Rickets from Vit D deficiency25(OH) < 10 ng/ml
Causes:
Umbalanced dietMalabsorptionsLack of exposition to lightChronical liver diseasesChronical kidney diseasesDrugs (anti convulsivants)
1,25-OH cholecalciferol receptor is in every cell or our body
Norman AW, Am J Clin Nutr, 2008
1,25-dihydroxyvitamin VDR receptor
Norman AW, Am J Clin Nutr, 2008
RFLPs Fok1 Bsm1,Taq1 Apa1 Cdx2, poly (A) Bgl1
Vit. D – Ormon D Pleiotropin D – Epigenetic agent D
Colecalciferol• Not active precursor, not hydroxilated
Calcidiol o 25(HO)Vit D - D2.• Inactive• Used for blood tests
Calcitriol o 1,25(HO) Vit.D - D3• Active form
25(OH)D=25-idrossivitamina D; 1,25(OH)2D=1,25-diidrossivitamina D
Cute (80%)Fegato
Rene
Dieta (~20%) Vitamina D3
Vitamina D2
Intestino Osso
ProD3 PreD3 Vitamina D3
25(OH)D
1,25(OH)2DPTH (+)
UVBSole
(+) Basso PO2–
4Garantisce un assorbimento
ottimale di calcio e fosforo Garantisce una
mineralizzazione ottimaleMantiene concentrazioni ottimali di calcio e
fosforo sierici
Funzioni metaboliche Funzioni neuromuscolari
Promuove la differenziazione
cellulare
modificato da Holick MF Osteoporos Int 1998
Vitamin D Metabolism
Nutritional sources of
We can obtain from food only< 20% of needed amount
80% of our Vit. D is comes from the sun light exposure and only from March to October in middle hours of the day at our
latitude.
024681012
Gen Feb Mar Apr Mag Giu Lug Ago Sett Nov Dic Mesi dell'anno
% d
i fot
otra
sfor
maz
ione
What Vit. D does ?Effetti epigenetici su oltre 2000 geni
Effetti extrascheletrici
Modulazione della risposta immunitaria
Modulazione della duplicazione
cellulare
CalcemiaFosforemia Endotelio
Aging Infiammazione
Effetti muscolo scheletrici
Metabolismo osseo
Assorbimento del calcio
Trofismo muscolare
Are there other natural substances with sinergistig activity ?
Effetti epigenetici su oltre 2000 geni
Effetti extrascheletrici
Modulazione della risposta immunitaria
Modulazione della duplicazione
cellulare
CalcemiaFosforemia Endotelio
Aging Infiammazione
Effetti muscolo scheletrici
Metabolismo osseo
Assorbimento del calcio
Trofismo muscolare
CurcuminaAcidi grassi ῳ3
Ca, Mg, AA, Fe, Zn, SeVitamine gruppo BVit. K
Vit. C, EchinaceaCurcuminaῳ3, Vit B,
Pleiotropic activity on more than 2.100 genes with scheletric and extra- scheletric activities
(1) Heaney et Al. Am. J. Nutr, 2003(2) Vitamin D for Health: A Global Perspective Arash Hossein-nezhad, Michael F. Holick Mayo Clinic proceedings.
Mayo Clinic 1 July 2013 (volume 88 issue 7 Pages 720-755 DOI: 10.1016/j.mayocp.2013.05.011)
Vit D and immunomodulation
Endocrinol Metab Clin North Am. 2010 Jun;39(2):365-79, Vitamin D and the immune system: new perspectives on an old theme. Hewison M
Effects of vitamin D on innate and adaptive immunity
Schematic representation of the principal innate and adaptive immune responses to a pathogenic challenge, and the positive or negative regulation of these responses by vitamin D. TLR, toll like receptor; DC, dendritic cell, M , macrophage; T-cell, T-lymphocyte; cyto T-cell, cytotoxic T-cell; B-cell, B-lymphocyte; Treg, regulatory T-cell
Vit. D and immunomodulation
Miller J, Gallo RL. Vitamin D and innate immunity, Dermatol. Therapy, 2010; 23:13-22
LA PRESENZA DI VITAMINA D E’ NECESSARIA PER L’ATTIVAZIONE DEI LINFOCITI B E PER IL RECLUTAMENTO DEI MACROFAGI
Published in 201510 Studies includedLack of evidence that Vit D is more effective than placeboMany possible biases (starting level of Vit D )
Can we mesure our Vit.D status ?Interpretazione dei livelli ematici di 25(OH)D (1)
Check PTH too !!!
Adami et al Bone 2009Adami et al Bone 2008 & Isaia et al OI 2003
Vit D carencies prevalence in Italy
0102030405060708090
100
<25nmol/l <35 nmol/l <50nmol/l <60 nmol/l <75 nmol/l
Prev
alen
ce P
erce
ntItaly Elderly Italy Young
Severe vitamin D deficiency is found in > 50% of elderly subjects and inadequate levels in >95%.Inadequate 25OHD values are found in > 50% of young “healthy” subjects.
Valore medio della 25(OH)D
Pazienti con valori di 25(OH)D <30 ng/mL
Pazienti con valori di 25(OH)D <12 ng/mL
16.8 ± 13.1 ng/mL (range 0.3-69.1)
78.3% (235/300)
41% (123/300)
Delle Sedie A et al, Clinical Cases in Mineral and Bone Metabolism 2006
Patients with rheumatologic diseases show lower values of vit. D (N=300)
EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the Tolerable Upper Intake Level of vitamin D. EFSA Journal 2012;10(7):2813. [45 pp.] doi:10.2903/j.efsa.2012.2813. Available online: www.efsa.europa.eu/efsajournal
Scientific Opinion on the Tolerable Upper Intake Level of vitamin D1 EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA)
In two studies in men, intakes between 234 and 275 μg/day were not associated with hypercalcaemia, and a no observed adverse effect level (NOAEL) of 250 μg/day was established
Upper Intake Level of vitamin D μg U.I.
Infants (0-1) 25 μg 1.000
Children (1-10) 50 μg 2.000
Adolescents (11-17) 100 μg 4.000
Adults 100 μg 4.000
Pregnant women 100 μg 4.000
Effect of cholecalcifelrol supplementation on blood 25(OH)Vit.D level
Larn 2016 Recommended intake for the Italian poulation 2012-2014
Why do we develope vit D deficiences?
How should we treatVit D deficiences?
http://www.reumatismo.org/index.php/reuma/article/viewFile/reumatismo.2011.129/510
http://www.pacinimedicina.it/wp-content/uploads/vitaminaD_brandi_michieliDM.pdf
http://www.efsa.europa.eu/it/efsajournal/pub/2813
Vit D and mortality in the elderly
3 years follow-up
6 years follow-up
Johansson et al, Osteoporos Int, 2012
“ Sarcopenia is a term that denotes the decline in muscle mass and strength that
occurs with healthy aging.”Rosenberg, Am. J. Clin. Nutr.
1989
“ Sarcopenia is part of normal agingand does not require a disease to occur,
although it is accellerated by chronic diseases.”
Roubenoff et al, J Gerontol 2000
Relation of vit D deficiency to cardiovascular risk factors, disease status, and incident cv events(death, heart failure, coronary artery disease/myocardial infarction, stroke)
Anderson et al, Am J Cardiol, 2010
Association between low serum 25-hydroxy-vitamin D and depression in a large sample of healthy adults: the Cooper Center Longitudinal StudyMayo Clinic Proceedings, 2011
Vit D deficiency and depression
Livelli più alti di vitamina D erano associati ad un rischio minore di depressione, al contrario, invece, di stati carenziali che sono risultati associati a maggiore probabilità di depressione, soprattutto nei soggetti che in passato avevano già sofferto di tale malattia.
Ai pazienti coinvolti veniva somministrato un questionario per valutare una possibile storia precedente di depressione e venivano valutati i seguenti parametri: • livelli sierici di 25(OH)D •sintomi depressivi, misurati mediante indice di depressione CES-D (Center for Epidemiologic Studies Depression Scale; un punteggio uguale o superiore a 10 indica depressione)
100 –
90 –
80 –
70 –
60 –
50 –
40 –
30 –
20 –
10 –
0
% asthmatic children with a desiderable level of Vitamin D
(at least 30 to 40 ng/mL)
9.3%
Verona = 45°
Vitamin D Serum Levels and Markers of Asthma Control in Italian Children Chinellato J Pediatr 2011;158:437
75 asthmatic children
25-hydroxyvitamin D
Spirometry
asthma control, according to GINA guidelines and with Childhood Asthma Control Test
Vit D and testosterone (free and total) in men
1362 uominiProporz. Diretta fino a 75/85 nmol/lNessuna stagionalità
Safety profile and vit. D intoxication:
Synergistic activity with:
• Nsaid’s and steroids• Omega 3• Boswellia• Curcumin
Inflammation anc chronic pain
• Omega3• Vit. B complex• Ginko biloba• Anti-oxidants
PeripheralNeuropatic pain
and neurodegeneration
• Glutammine• Probiotics and prebiotics• Anti-oxidants• Curcumin
Gastrointestinal health
• Glucosammine• Chondroitine• Boswellia serrata• Curcumin
Joints Health
Curcuma longa
Boswellia serrata
• Omega 3 (EPA and DHA)
Zingiber officinale
Natural substances with anti-inflammatory activity
Curcumin: THE active principle of turmeric
(1,7-bis (4-hydroxy-3-methoxy-phenyl) hepta-1,6-diene-3,5-dione)
Turmeric powdercontains 3-7% of Curcuminoidsessential oils and fibers
8.770 studies shows pleiotroitropic effects of curcumin (Pubmed)
Inflammatory targets modulated by curcumin
23
24
25
26
27
28
29
02468
1012141618
02468
101214161820
“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 di
sedi
men
tazio
ne e
ritro
cita
ria (E
SR)
- 11% - 8%
Significative reduction ofDisease Activity Score (DAS)
Significative reduction ofJoints pain
- 83%- 69%
- 97% - 89%
Significative reduction ofJoints swelling
% In
cide
nza
% In
cide
nza
Curcuminextract Diclofenac1000 mg 100 mg
p < 0.05 p < 0.05 p < 0.05
Curcuminextract Diclofenac1000 mg 100 mg
Curcuminextract Diclofenac1000 mg 100 mg
Ibuprofen Curcumina280290300310320330340350360
° 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
MobilityDistance covered in 6 minutes
(Time 0 and after 4 weeks)
p = 0,010
Met
ers w
alke
d in
6 m
inut
es
Chronic Pain(Time 0 and after 4
weeks)
Ibuprofen Curcumina0
1
2
3
4
5
6
p = 0,018
% In
cide
nce
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.
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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