Ipovitaminosi D ed Obesità

1. VITAMINA D COME FATTORE DI
RISCHIO POTENZIALE
NELL’OBESITA’
Massimiliano Andrioli
EndocrinologiaOggi, Roma, Lecce
Endocrinologia, Istituto Auxologico Italiano, Milano

2. TIPI DI VITAMINA D
• vitamina D3 o Colecalciferolo (animale)
• vitamina D2 o Ergocalciferolo (vegetale)
• 80-90% produzione endogena
• 10-20% alimentare (animale/ vegetale)

3. 7-Dehydrocholesterol7-Dehydrocholesterol Pre-Vitamin DPre-Vitamin D33 Vitamin DVitamin D33
EpidermisEpidermis
LatitudeLatitude
PollutionPollution
ClothingClothing
Melanin pigmentationMelanin pigmentation
Duration of exposureDuration of exposure
FISIOLOGIA

4. FISIOLOGIA
calcifediolo
calcitriolo
colecalciferolo

5. Colecalciferolo (vitamina D3)
• Di-base gtt 10.000 UI/ml (1 gtt = 250 IU, 1 mcg = 40 UI)
• Di-base flaconcino 25.000 IU
• Di-base fl os/im 100.000-300.000 UI
Calcifediolo (25-OH-colecalciferolo)
• Didrogyl gtt (uso selettivo)
NB 5 ug (200 IU) colecalciferolo = 1 ug (40 IU) calcifediolo
Calcitriolo (1,25 OH vitamina D3)
• Rocaltrol 0,25-0,50 ug cpr (uso selettivo)
• 1-alfa-OH-colecalciferolo (alfa-calcidolo)
• Dediol/Diserinal cpr 0,25-1 ug (uso selettivo)
Ergocalciferolo (Vitamina D2 )
• Ostelin fl os/im 400.000 UI (meno efficace, poco utilizzata)
FARMACI

6. FUNZIONE
1,25(OH)1,25(OH)22DD
BoneBoneDietary calciumDietary calcium IntestinesIntestines

7. Bone Density and Fractures
– Risk of osteoporosis may be reduced with adequate intake of vitamin
D and calcium.
– Studies support the concept that vitamin D at doses between 700 and
800 IU/d with calcium supplementation effectively increase hip bone
density and reduced fracture risk, whereas lower vitamin D doses
may have less effect.
VITAMINA D - OSSO

8. Cells containing 25OH-VitD3-1-alpha-OHase
Breast, prostate, lung, skin, lymph nodes, colon, pancreas, adrenal
medulla, brain, placenta
» Holllick MF. Am J Clin Nutr. 2004. 79(3):362.
» Zehnder et al. J Clin Endocrin Metab. 2001;86(2)
Cells containing Nuclear VDR
Pancreatic islet cells, monocytes, transformed B cells, activated T
cells, neurons, prostate, ovaries, pituitary, aortic endothelium,
placenta, skeletal muscle cells.
» Zittermann A. Br J Nutr. 2003;89(5):552.
» Bischoff HA, et al. Histochem J 2001;33:19.
EFFETTI EXTRASCHELETRICI

9. • Involved in cellular growth, differentiation and apoptosis
• Simulates insulin secretion
• Modulates the immune system.
• Reduces inflammation
• Muscle development
EFFETTI EXTRASCHELETRICI

10. Role in Cancer Prevention
– Low intake of vitamin D and calcium has been associated with an
increased risk of non-Hodgkin lymphomas, colon, ovarian, breast,
prostate, and other cancers.
– The anti-cancer activity of vitamin D is thought to result from its role
as a nuclear transcription factor that regulates cell growth,
differentiation, apoptosis and a wide range of cellular mechanisms
central to the development of cancer. These effects may be mediated
through vitamin D receptors expressed in cancer cells.
– Vitamin D is not currently recommended for reducing cancer risk
VITAMINA D - TUMORI
Role in All Cause Mortality
–Researches concluded that having low levels of vitamin D
(<17.8 ng/mL) was independently associated with an increase in all-
cause mortality in the general population.
VITAMINA D – MORTALITA’

11. Autoimmune Disease
– Vitamin D supplementation is associated with a lower risk of autoimmune
diseases.
– In a Finnish birth cohort study of 10,821 children, supplementation with
vitamin D at 2000 IU/d reduced the risk of type 1 diabetes by
approximately 78%, whereas children who were at risk for rickets had a
3-fold higher risk for type 1 diabetes.
– In a case-control study of 7 million US military personnel, high circulating
levels of vitamin D were associated with a lower risk of multiple sclerosis.
– Similar associations have also been described for vitamin D levels and
rheumatoid arthritis.
VITAMINA D – AUTOIMMUNITA’

12. Role in Cardiovascular Diseases
– Vitamin D deficiency activates the renin-angiotensin-aldosterone
system and predisposes to hypertension and left ventricular
hypertrophy.
– Vitamin D deficiency increases PTH, which increases insulin
resistance secondary to down regulation of insulin receptors and is
associated with diabetes, hypertension, inflammation, and increased
cardiovascular risk.
VITAMINA D - CARDIOVASCOLARE
Role in Reproductive Health
– Vitamin D deficiency early in pregnancy is associated with a five-fold
increased risk of preeclampsia.
VITAMINA D - RIPRODUZIONE

13. Robert P. 2008. Vitamin D in Health and Disease. Clin J Am Soc Nephrol 3:1535-1541.
Disorder Strength of Evidence
Osteoporosis ++++
Falls ++++
Type 1 DM ++
Cancer ++++
Autoimmune diseases ++
Hypertension +++
Periodontal disease ++++
Multiple sclerosis ++
Susceptibility/poor response
to infection
++++
Osteoarthritis ++
DISORDINI CAUSATI O AGGRAVATI DA
IPOVITAMINOSI D

14. VITAMINA D - PUBBLICAZIONI

15. VITAMINA D- OBESITA’

16. VITAMINA D
OBESITA’
RISCHIO CARDIOVASCOLARE

17. (Rizzoli R. Current Medical Research & Opinion 2013)
DEFINIZIONE

18. - increased age
- female sex
- darker skin pigmentation
- reduced sun exposure
- seasonal variation
- distance from the equator
- inter-assay and inter-laboratory 25(OH)D variability
25OHD ASSESSMENT

19. • Poor dietary intake of vitamin D
• Lower sun exposure
• Sedentary lifestyle
• Clothing practices
• Decreased oral absorption
• Decreased cutaneous synthesis
• Increased clearance
• Enhanced production of 1,25(OH) D. Negative feedback on 25(OH)D
• 25(OH)D may increase glucocorticoid which regulates adipose tissue
• Vitamin D decreases PPAR-gamma, leading to other metabolic processes
in the preadipocyte.
EZIOLOGIA

20. • Olson et al JCEM 2011
– 92% of obese subjects had a 25(OH)D level below 30 ng/ml vs
68% in non overweight children
– 50% of obese subjects were below 20 ng/l vs 22% in non
overweight children
• Alemzedeh et al Metabolism 2008
– 74% had 25(OH)D levels less than 30 ng/ml and 32.3% had
25(OH)D < 20 ng/ml
EPIDEMIOLOGIA

21. – selective deposition of vitamin D, a lipophilic molecule, in subcutaneous
and visceral adipose tissue
– BMI and body fat were inversely related to serum 25(OH) vitamin D
– positive correlation between serum and fat tissue 25(OH) vitamin
– visceral compartment volume more closely associated with vitamin D
deficiency compared with subcutaneous fat
– independent association between hypovitaminosis D and dysmetabolic
conditions such as MS, T2D, hypertension and liver steatosis
– hypovitaminosis D has been hypothesized as a primary cause of obesity
VITAMINA D - OBESITA’
- obesity leads to lower vitamin D levels and not the other way around
Vimaleswaran, PLoS Med. 2013

22. Proteins linking vitamin D to obesity:
- vitamin D receptor
- toll-like receptors
- renin-angiotensin system
- apolipoprotein E
- vascular endothelial growth factor
- poly (DP-ribose) polymerase-1
IPOVITAMINOSI D – GENETICA
Vitamin D cell-signaling mechanisms:
- matrix metalloproteinases
- mitogen-activated protein kinase pathways
- reduced form of nicotinamide

23. IPOVITAMINOSI D – SINDROME METABOLICA
– Vitamin D insufficiency involves more than 75% of patients with metabolic
syndrome (MS)
– serum 25(OH) vitamin D3 levels are significantly lower in obese patients affected
by MS than in obese subjects without MS
– A powerful association between hypovitaminosis D and MS in obese patients
independently from body fat mass and its clinical correlates.
– The association between low 25(OH) D3 levels and MS is not merely induced by
vitamin D deposition in fat tissue
– active form of vitamin D3 exerts an insulinsensitizing action by increasing the
expression of insulin receptors in peripheral tissues and facilitating insulin-
mediated glucose transport.
– In addition, vitamin D3 directly regulates the free fatty acids (FFA) metabolism
acting on the PPAR and improves insulin resistance induced by FFA.
– Hypovitaminosis D represent a crucial independent determinant of MS.

24. IPOVITAMINOSI D – ADIPONECTINA
– Lower vitamin D and adiponectin levels were strongly associated with
metabolic risk factors and obesity in Turkish children and adolescent

25. IPOVITAMINOSI D – IPERTENSIONE
- inverse association of vitamin D levels with the renin-angiotensin-
aldosterone system activity
- endothelial function
- secondary hyperparathyroidism

26. 60
70
80
90
100
110
120
0 10 20 30 40 50 60 70 80
25 OH(D) (ng/mL)
FastingGlucose(mg/dL)
Johnson et al, Journal of Pediatrics 2010
VITAMINA D - GLICEMIA

27. VITAMINA D - DIABETE
– low vitamin D levels high risk of developing diabetes in the future
– VDR, 1-α-hydroxylase expressed in pancreatic beta cells, potential role of vitamin
D on beta cell function
– calcium crucial for insulin synthesis and secretion
– vitamin D-induced stimulation of osteocalcin, which may improve insulin sensitivity
– the currently available literature on vitamin D does not support the notion that
vitamin D supplementation is useful for the prevention and/or treatment of
diabetes mellitus

28. – Vitamin D treatment of animals with diabetes mellitus type 1 slows the progression
of diabetes
– High doses of vitamin in high risk-group children reduces diabetes incidence
VITAMINA D - DIABETE

29. 20
40
60
80
100
120
140
0 10 20 30 40 50 60 70 80
25 OH(D) (ng/mL)
HDL(mg/dL)
VITAMINA D – COLESTEROLO HDL
– association of vitamin D deficiency with lower high density lipoprotein (HDL)
– higher triglycerides
– higher apolipoprotein E levels
– no significant effect on blood lipids when vitamin D supplementation

30. IPOVITAMINOSI D – TRATTAMENTO

32. In generale: forme inattive (non 1-alfa-idrossilate)
•Colecalciferolo
•Calcifediolo (25OHD3)
Tre indicazioni alla terapia con forme attive (1-alfa-idrossilate)
•Calcitriolo
•1-alfa-calcidolo:
- IRC in stadio avanzato
- ipoparatiroidismo cronico
- malassorbimento grave
Adami S et al, Reumatismo 2011
IPOVITAMINOSI D – TRATTAMENTO

33. CONCLUSIONI
- ipovitaminosi D è frequente in obesità
- ipovitaminosi D è una conseguenza
- ipovitaminosi D si associa a: MS, ipertensione, diabete,
ipercolesterolemia, rischio CV
- trattamento integrativo

34. GRAZIE PER L’ATTENZIONE…..
www.endocrinologiaoggi.it