Diapositiva 1

IV Congresso Nazionale AINAT
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Vitamina D e Cervello Senile:
effetti protettivi e curativi
Vincenzo Manna
Docente di Neurologia e Neuropsicologia
Corso di Laurea in Logopedia Ariccia
“Sapienza” Università di Roma
IV Congresso Nazionale AINAT
NAPOLI 17-18 dicembre 2010
7-Deidrocolesterolo
Colecalciferolo
Ergocalciferolo
La vitamina D è un insieme di
pro-ormoni liposolubili
costituito da 5 diverse vitamine:
vitamina D1, D2, D3, D4 e D5.
Le due più importanti forme nella
quale la vitamina D si può trovare
sono
la vitamina D2 (ergocalciferolo) e
la vitamina D3 (colecalciferolo),
entrambe le forme
dall'attività biologica
molto simile.
IV Congresso Nazionale AINAT
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7-Deidrocolesterolo
Colecalciferolo
Ergocalciferolo
Il colecalciferolo (D3), derivante dal
colesterolo, è sintetizzato negli
organismi animali, mentre
l'ergocalciferolo (D2) è di provenienza
vegetale.
La vitamina D sintetizzata a partire da
precursori assunti attraverso la dieta e
dall’ esposizione solare è presente in
una forma biologicamente non attiva e
deve subire due reazioni
di idrossilazione
per essere trasformata nella
forma biologicamente
attiva, il calcitriolo.
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7- Deidro colesterolo
Gli studi strutturali hanno permesso di identificare
le due forme della vitamina D e che
dall'irradiazione del 7- deidrocolesterolo si
produce il 1 - 25 diidrossi-colecalciferolo,
mentre l'ergocalciferolo viene formato quando i
raggi ultravioletti colpiscono la sua provitamina
d’origine vegetale, l‘ergosterolo.
L'assorbimento della vitamina D segue gli
analoghi processi cui le altre vitamine
liposolubili sono sottoposte.
Essa, infatti, viene inglobata nelle micelle
formate all'incontro dei lipidi idrolizzati con la
bile, entra nell‘epitelio intestinale dove viene
incorporato nei chilomicroni i quali entrano
nella circolazione linfatica.
calcitriolo
1- 25 diidrossi
colecalciferolo
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1- 25 diidrossi
colecalciferolo
In vari tessuti il colecalciferolo subisce una
reazione di idrossilazione con formazione
di 25-idrossicolecalciferolo [25(OH)D] il
quale passa nella circolazione generale
e si lega ad una proteina trasportatrice
specifica (vitamin D binding protein, DBP).
Arrivato nel rene, il 25 (OH)D può subire due
diverse reazioni di idrossilazione, catalizzate da
differenti idrossilasi (la 1 alfa-idrossilasi e la 24idrossilasi), che danno origine, rispettivamente,
all‘1,25-diidrossicolecalciferolo [1,25(OH)D]
(calcitriolo), la componente attiva, ed al 24,25
diidrossicolecalciferolo [24,25(OH)D], una forma
inattiva.
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I raggi ultravioletti favoriscono la conversione del 7deidrocolesterolo che può dare origine al colecalciferolo ma
anche a due prodotti inattivi: il lumisterolo ed il tachisterolo.
A livello della cute si forma l'altra forma attiva della vitamina D,
l'ergocalciferolo, tramite trasformazione dell'ergosterolo.
La quantità di D3 e D2 prodotti dipende dalle radiazioni
ultraviolette (sono più efficaci quelle comprese tra 290 e 315 nm),
dalla superficie cutanea esposta, dal suo spessore e
pigmentazione e dalla durata della permanenza alla luce.
Le forme principali che costituiscono il gruppo vitaminico D:
vitamina D1 : composto costituito in parti 1:1 di ergocalciferolo e lumisterolo
vitamina D2 : calciferolo
vitamina D3 : COLECALCIFEROLO (calcitriolo)
1- 25 diidrossi-colecalciferolo
vitamina D4 : diidroergocalciferolo
vitamina D5 : sitocalciferolo
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La vitamina D favorisce il riassorbimento di calcio a
livello renale, l'assorbimento intestinale di fosforo e
calcio ed i processi di mineralizzazione dell’osso ed
anche di differenziazione di alcune linee cellulari e in
alcune funzioni neuromuscolari (anche se questi due
ultimi punti devono ancora essere chiariti).
Il funzionamento dell' 1,25(OH)D è alquanto
anomalo per una vitamina in quanto agisce
secondo le caratteristiche proprie degli
VDR
ormoni steroidei:
recettore nucleare
che va a stimolare la produzione di varie proteine…
entra nella cellula e si va a legare ad un
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La regolazione dei livelli di calcio e fosforo
nell'organismo avviene insieme all'azione di due
importanti ormoni: la calcitonina ed il paratormone.
La calcitonina ha azioni opposte a quelle della
vitamina D, favorendo l'eliminazione urinaria e la
deposizione di calcio nelle ossa. Ciò si traduce in
una diminuzione dei livelli plasmatici di calcio.
Il paratormone, invece, inibisce il riassorbimento
renale dei fosfati,
aumenta quello del calcio e
stimola il rene a produrre
24,25(OH) D; a livello dell'osso,
promuove il rilascio di calcio.
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La produzione di calcitonina e paratormone e di vitamina
D è strettamente dipendente dalla concentrazione
plasmatica di calcio:
una condizione di ipocalcemia stimola la produzione di
paratormone e di 24,25(OH)D.
Un aumento del calcio plasmatico, invece, favorisce la
sintesi di calcitonina.
Il delicato equilibrio che si viene a creare determina una
buona regolazione dei processi di mineralizzazione.
Sembra, infine, che la vitamina D possa promuovere la
differenziazione dei cheratinociti dell'epidermide e degli
osteoclasti ossei e, forse, detiene anche un'azione
antiproliferativa.
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?
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La Vitamina D è un ormone neurosteroide
BRAIN
BRAIN
VDR (Vitamin D Receptor)
BRAIN
Il cervello produce ed inattiva il neurormone Vitamina D
Il SNC è ricco di recettori specifici VDR (Vitamin D Receptor)
Il cervello rappresenta uno specifico target della Vitamina D
La Vitamina D tramite i VDR induce i geni cerebrali a modulare i neuromediatori
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VDR (Vitamin D Receptor)
knockout mouse strains
• Tokyo strain (1997) Yoshizawa et al. ablated exon 2 (1st zinc finger)
• Boston strain (1997) Li et al. ablated exons 3-5 (2nd zinc finger)
• Leuven strain (2001) Van Cromphaut et al. ablated exons 1-2 (1st zinc finger)
• Munich strain (2002) Erben et al. ablated 1st zinc finger
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Altered behaviours in
“Tokyo”
VDR knockout mice
• Increased anxiety.
Kalueff et al. (2004)
• Specific motor impairment (poor swimming).
Kalueff et al. (2004)
• Activated grooming.
Kalueff et al. (2004)
• Impaired patterning (disturbed cephalocaudal sequencing) of grooming. Kalueff et al. (2005)
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Increased anxiety in VDR KO mice
Tiina Keisala, Allan V Kalueff, PhD, 2008
• Reduced “open field” horizontal exploratory activity
• Reduced “open field” vertical activity
• Strong food neophobia (Minasyan et al., 2007)
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)
Tiina Keisala, Allan V Kalueff, PhD, 2008
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Tiina Keisala, Allan V Kalueff, PhD, 2008
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Tiina Keisala, Allan V Kalueff, PhD, 2008
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VDR KO mouse
Tiina Keisala, Allan V Kalueff, PhD, 2008
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Tiina Keisala, Allan V Kalueff, PhD, 2008
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Tiina Keisala, Allan V Kalueff, PhD, 2008
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The 1,25-dihydroxyvitamin D3 receptor (VDR),
and 1a-hydroxylase (1a-OHase),
the enzyme responsible for the formation of the active
vitamin in the human brain
were studied by immunofluorescence.
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The receptor and the enzyme were found in both
neurons and glial cells.
The VDR was restricted to the nucleus
1a-OHase was distributed throughout the
cytoplasm.
D.W. Eyles et al. / Journal of Chemical Neuroanatomy 29 (2005) 21–30
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Many regions contained equivalent amounts of
both the VDR and 1a-OHase,
however the macrocellular cells within the nucleus
basalis of Meynert (NBM) and the Purkinje cells in
the cerebellum expressed 1a-OHase in the
absence of VDR.
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Substantia nigra
VDR
Substantia nigra
1 alpha hydroxylase
The strongest
immunohistochemical
staining for both the
receptor and enzyme
was in the hypothalamus
and in the large
dopaminergic
neurons within the
substantia nigra.
D.W. Eyles et al. / Journal of Chemical Neuroanatomy 29 (2005) 21–30
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The distribution of the VDR in human brain was strikingly similar to
that reported in rodents.
The widespread distribution of 1a-OHase
and the VDR suggests that Vitamin D may
have autocrine/paracrine properties in the
human brain.
The observed distribution of the VDR is consistent
with the proposal that Vitamin
D operates in a
similar fashion to the known neurosteroids.
Despite a growing body of evidence that Vitamin D is involved in
mammalian brain functioning, there has been a lack of direct
evidence about its role in the human brain.
D.W. Eyles et al. / Journal of Chemical Neuroanatomy 29 (2005) 21–30
IV Congresso Nazionale AINAT
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Vitamin D and the brain
Over 900 different genes
are now known to be able to bind the vitamin D receptor, through which
vitamin D mediates its effects.
Major depression is associated with low vitamin D levels (Stumpf, 1972)
Several studies have reported mood-elevating effects of vitamin D therapy VDR
genetic deficits are associated with depression, schizophrenia and suicidality
(Ozer et al., 2005)
VDR knockout mouse data strongly support the role of vitamin D dysfunctions in
stress-related brain disorders.
Vitamin D supplementation is crucial for groups
whose vitamin D status is exceptionally low:
infants, the elderly and blacks.
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Tiina Keisala, Allan V Kalueff, PhD, 2008
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Altri effetti biologici riportati della vitamina D
nel sistema nervoso includono:
1. la biosintesi di fattori neurotrofici;
2. l'inibizione dell’ossidonitrico-sintasi inducibile;
3. l’aumento dei livelli di glutatione;
suggerendo un ruolo di disintossicazione
cerebrale per il neurormone, vitamina D.
Slinin Y et al. Neurology 74(1): 27-32, 2010
IV Congresso Nazionale AINAT
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Serum 25-Hydroxyvitamin D
Concentration and Cognitive Impairment
David J. Llewellyn, Kenneth M. Langa, Iain A. Lang
Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
Vitamin D may be of interest in the prevention of cognitive
impairment, though previous findings are inconclusive.
Participants were
1766 adults aged 65 years
and older from the Health Survey for England 2000, a
nationally representative population-based study.
Cognitive impairment was assessed using the Abbreviated
Mental Test Score.
The cross-sectional relation of serum 25-hydroxyvitamin D
quartiles to cognitive impairment was modeled using logistic
regression.
J Geriatr Psychiatry Neurol 2009; 22 (3): 188-195.
IV Congresso Nazionale AINAT
NAPOLI 17-18 dicembre 2010
Serum 25-Hydroxyvitamin D
Concentration and Cognitive Impairment
David J. Llewellyn, PhD, Kenneth M. Langa, MD, PhD, and Iain A. Lang, PhD
Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
In all, 212 participants (12%) were cognitively impaired.
Odds ratios (95% confidence intervals) for cognitive impairment in the
first (8–30 nmol/L), second (31–44 nmol/L), and third (45–65 nmol/L)
quartiles of serum 25-hydroxyvitamin D compared with the fourth (66–
170 nmol/L) were 2.3 (1.4–3.8), 1.4 (0.8–2.4), and 1.1 (0.6–1.9), after
adjustment for age, sex, education, ethnicity, season of testing, and
additional risk factors for cognitive impairment (P for linear trend =
.001).
Data suggest low serum 25-hydroxyvitamin D
is associated with increased odds of cognitive
impairment.
J Geriatr Psychiatry Neurol 2009; 22 (3): 188-195.
IV Congresso Nazionale AINAT
NAPOLI 17-18 dicembre 2010
Serum 25-Hydroxyvitamin D Concentration and Cognitive Impairment
David J. Llewellyn, Kenneth M. Langa, Iain A. Lang
Department of Public Health and Primary Care, University of Cambridge, UK
J Geriatr Psychiatry Neurol 2009; 22 (3): 188-195.
IV Congresso Nazionale AINAT
NAPOLI 17-18 dicembre 2010
I risultati di una nuova analisi utilizzando i dati provenienti
dal National Health and Nutrition Third Survey (NHANES III)
sostengono che la carenza di vitamina D può essere associata ad
un aumentato rischio di declino cognitivo negli anziani
americani.
I risultati del NHANES III, sono stati presentati alla Alzheimer's
Association International Conference nel luglio 2010.
Essi dimostrano che bassi livelli di vitamina D sono associati ad
un conseguente declino cognitivo nel corso di 6 anni di followup.
Nel loro insieme, sembra che “bassi livelli di vitamina D
provocano veri danni al cervello” come ha sostenuto
l'autore David J. Llewellyn, PhD, dell’Università di Exeter
Peninsula Medical School nel Regno Unito.
J Geriatr Psychiatry Neurol 2009; 22 (3): 188-195.
IV Congresso Nazionale AINAT
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25-Hydroxyvitamin D levels and cognitive
performance and decline in elderly men.
Slinin Y et al. Veterans Dr. (111J), Minneapolis, MN 55417, USA.
OBJECTIVE
To test the hypothesis that lower 25-hydroxyvitamin D [25(OH)D]
levels are associated with a greater likelihood of cognitive
impairment and risk of cognitive decline.
METHODS
They measured 25(OH)D and assessed cognitive function using
the Modified Mini-Mental State Examination (3MS) and Trail Making
Test Part B (Trails B) in a cohort of 1.604 men enrolled in the
Osteoporotic Fractures in Men Study and followed them for an
average of 4.6 years for changes in cognitive function.
Neurology. 2010 Jan 5;74(1):33-41.
IV Congresso Nazionale AINAT
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25-Hydroxyvitamin D levels and cognitive
performance and decline in elderly men.
Slinin Y et al. Veterans Dr. (111J), Minneapolis, MN 55417, USA.
RESULTS
In a model adjusted for age, season, and site, men with lower 25(OH)D levels seemed to have a
higher odds of cognitive impairment, but the test for trend did not reach significance
(impairment by 3MS: odds ratio [OR] 1.84, 95% confidence interval [CI] 0.81-4.19 for quartile [Q]
1; 1.41, 0.61-3.28 for Q2; and 1.18, 0.50-2.81 for Q3, compared with Q4 [referent group; p trend =
0.12]; and impairment by Trails B: OR 1.66, 95% CI 0.98-2.82 for Q1; 0.96, 0.54-1.69 for Q2; and
1.30, 0.76-2.22 for Q3, compared with Q4 [p trend = 0.12]). Adjustment for age and education
further attenuated the relationships.
There was a trend for an independent association between lower 25(OH)D
levels and odds of cognitive decline by 3MS performance (multivariable OR 1.41, 95% CI 0.892.23 for Q1; 1.28, 0.84-1.95 for Q2; and 1.06, 0.70-1.62 for Q3, compared with Q4 [p = 0.10]), but
no association with cognitive decline by Trails B.
CONCLUSION
We found little evidence of independent associations between
lower 25-hydroxyvitamin D level and baseline global and executive
cognitive function or incident cognitive decline.
Neurology. 2010 Jan 5;74(1):33-41.
IV Congresso Nazionale AINAT
NAPOLI 17-18 dicembre 2010
Association of vitamin D deficiency with
cognitive impairment in older women:
cross-sectional study.
Annweiler C et al. Department of Internal Medicine and Geriatrics, Angers University
Hospital, France.
OBJECTIVE:
The association between low serum 25-hydroxyvitamin D [25(OH)D] concentration and cognitive
decline has been investigated by only a few studies, with mixed results. The objective of this
cross-sectional population-based study was to examine the association between serum 25(OH)D
deficiency and cognitive impairment while taking confounders into account.
METHODS:
752 women aged > or =75 years
The subjects,
from the
Epidémiologie de l'Ostéoporose (EPIDOS) cohort, were divided into 2 groups according to serum
25(OH)D concentrations (either deficient, <10 ng/mL, or nondeficient, > or =10 ng/mL). Cognitive
impairment was defined as a Pfeiffer Short Portable Mental State Questionnaire (SPMSQ) score <8.
Age, body mass index, number of chronic diseases, hypertension, depression, use of
psychoactive drugs, education level, regular physical activity, and serum intact parathyroid
hormone and calcium were used as potential confounders.
Neurology. 2010 Jan 5;74(1):27-32.
IV Congresso Nazionale AINAT
NAPOLI 17-18 dicembre 2010
Association of vitamin D deficiency with
cognitive impairment in older women:
cross-sectional study.
Annweiler C et al. Department of Internal Medicine and Geriatrics, Angers University
Hospital, France.
RESULTS
Compared with women with serum 25(OH)D concentrations > or =10 ng/mL (n = 623), the women
with 25(OH)D deficiency (n = 129) had a lower mean SPMSQ score (p < 0.001) and more often had
an SPMSQ score <8 (p = 0.006). There was no significant linear association between serum
25(OH)D concentration and SPMSQ score (beta = -0.003, 95% confidence interval -0.012 to 0.006, p
= 0.512). However, serum 25(OH)D deficiency was associated with cognitive impairment (crude
odds ratio [OR] = 2.08 with p = 0.007; adjusted OR = 1.99 with p = 0.017 for full model; and adjusted
OR = 2.03 with p = 0.012 for stepwise backward model).
CONCLUSIONS
25-Hydroxyvitamin D deficiency was associated
with cognitive impairment in this cohort of
community-dwelling older women.
Neurology 74(1): 27-32, 2010
IV Congresso Nazionale AINAT
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Association between 25-hydroxyvitamin D levels and
cognitive performance in middle-aged and older men.
Lee DM et al. ARC Epidemiology Unit, The University of Manchester, UK.
BACKGROUND
Although there is evidence that vitamin D inadequacy may be linked to adverse
cognitive outcomes, results from studies on this topic have been inconsistent. The
aim of this trial was to examine the association between 25-hydroxyvitamin D
(25(OH)D) levels and cognitive performance in middle-aged and older European
men.
METHODS
This population-based cross-sectional study included 3,369
men aged
40-79 years from eight centres enrolled in the European Male Ageing Study.
Cognitive function was assessed using the Rey-Osterrieth Complex Figure (ROCF)
test, the Camden Topographical Recognition Memory (CTRM) test and the Digit
Symbol Substitution Test (DSST). Serum 25(OH)D levels were measured by
radioimmunoassay. Additional assessments included measurement of physical
activity, functional performance and mood/depression. Associations between
cognitive function and 25(OH)D levels were explored using locally weighted and
linear regression models.
Neurol Neurosurg Psychiatry. 2009 Jul;80(7):722-9.
IV Congresso Nazionale AINAT
NAPOLI 17-18 dicembre 2010
Association between 25-hydroxyvitamin D levels and
cognitive performance in middle-aged and older men.
Lee DM et al. ARC Epidemiology Unit, The University of Manchester, UK.
RESULTS
In total, 3,133 men (mean (+/-SD) age 60+/-11 years) were included in the analysis.
The mean (+/-SD) 25(OH)D concentration was 63+/-31 nmol/l. In age-adjusted linear
regressions, high levels of 25(OH)D were associated with high scores on the copy
component of the ROCF test (beta per 10 nmol/l = 0.096; 95% CI 0.049 to 0.144), the
CTRM test (beta per 10 nmol/l = 0.075; 95% CI 0.026 to 0.124) and the DSST (beta per
10 nmol/l = 0.318; 95% CI 0.235 to 0.401). After adjusting for additional confounders,
25(OH)D levels were associated with only score on the DSST (beta per 10 nmol/l =
0.152; 95% CI 0.051 to 0.253). Locally weighted and spline regressions suggested the
relationship between 25(OH)D concentration and cognitive function was most
pronounced at 25(OH)D concentrations below 35 nmol/l.
CONCLUSION
In this study, lower 25(OH)D levels were associated with poorer
performance on the DSST.
Further research is warranted to determine whether vitamin D sufficiency
might have a role in preserving cognitive function in older adults.
Neurol Neurosurg Psychiatry. 2009 Jul;80(7):722-9.
IV Congresso Nazionale AINAT
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Serum Vitamin D and the Risk of Parkinson Disease
Paul Knekt et al. National Institute for Health and Welfare in Helsinki (Finland)
Previous studies have reported that lower blood levels of Vitamin D (measured
as serum 25-hydroxyvitamin D) are observed people with Parkinson's Disease,
as compared to healthy counterparts.
The team assessed 3,175 men and women, ages
did not have Parkinson’s Disease at the study’s start.
50 to 79 years, who
The subjects were followed for a 29-year period, during which
the incidence of Parkinson’s was tracked.
The researchers determined serum 25-hydroxyvitamin D level from frozen blood samples
stored at the study’s start, and used a mathematical model to estimate the relationship
between serum vitamin D concentration and Parkinson disease incidence. Individuals with
higher serum vitamin D concentrations showed a reduced risk of Parkinson disease. After
adjustment for confounding factors, the relative risk of Parkinson's disease between the
highest and lowest quartiles of serum 25-hydroxyvitamin D levels was 0.33.
The team concludes that: “The results are consistent with the
suggestion that high vitamin D status provides protection
against Parkinson disease.”
Arch Neurol, Jul 2010; 67: 808 - 811.
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Vitamin D supplementation improves neuromuscular function in older people who fall
Jugdeep K. Dhesi et al. Elderly Day Hospital, Thomas Guy House, Guys Hospital, St Thomas Street, London
SE1, UK
Background
Vitamin D supplementation reduces the incidence of fractures in older adults. This
may be partly mediated by effects of vitamin D on neuromuscular function.
Objective
To determine the effects of vitamin D supplementation on aspects of
neuromuscular function known to be risk factors for falls and fractures.
Design
Randomised, double-blind, placebo-controlled study.
Setting
Falls clinic taking referrals from general practitioners and accident and emergency
department.
Subjects
139 ambulatory subjects (≥65 years) with a history of falls and 25hydroxyvitamin D (25OHD) ≤12 μg/l.
Oxford Journals, Medicine, Age and Ageing, Volume 33, Issue 6 pp. 589-595.
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Vitamin D supplementation improves neuromuscular function in older people who fall
Jugdeep K. Dhesi et al. Elderly Day Hospital, Thomas Guy House, Guys Hospital, London, UK
Intervention
Patients were randomised to receive a single
intramuscular injection of 600,000 i.u. ergocalciferol
or placebo.
Outcome measures
assessments including biochemistry, postural sway,
choice reaction time (CRT), aggregate functional
performance time (AFPT), and quadriceps strength
were carried out at baseline and 6 months postintervention.
Oxford Journals, Medicine, Age and Ageing, Volume 33, Issue 6 pp. 589-595.
IV Congresso Nazionale AINAT
NAPOLI 17-18 dicembre 2010
Vitamin D supplementation improves neuromuscular function in older people who fall
Jugdeep K. Dhesi et al. Elderly Day Hospital, Thomas Guy House, Guys Hospital, London, UK
Results
Baseline characteristics were comparable between both groups. 25OHD
in the treatment group increased significantly at 6 months. AFPT
deteriorated in the control group and improved in the intervention
group, representing a significant difference between groups (+6.6 s
versus –2.0 s, t = 2.80, P < 0.05). Similar changes were observed for
CRT (−0.06 s versus +0.41 s, t = −2.52, P < 0.01) and postural sway
(+0.0025 versus −0.0138, t = 2.35, P < 0.02). There was no significant
difference in muscle strength change between groups (−10 N versus
−2 N, t = −1.26, ns). A significant correlation between change in AFPT
and change in 25OHD levels was observed (r = 0.19, P = 0.03). There
was no significant difference in the number of falls (0.39 versus 0.24,
t = 1.08, P = 0.28) or fallers (14 versus 11, P = 0.52) between two
groups.
Oxford Journals, Medicine, Age and Ageing, Volume 33, Issue 6 pp. 589-595.
IV Congresso Nazionale AINAT
NAPOLI 17-18 dicembre 2010
Vitamin D supplementation improves neuromuscular function in older people who fall
Jugdeep K. Dhesi et al. Elderly Day Hospital, Thomas Guy House, Guys Hospital, St Thomas Street, London
SE1, UK
Conclusions
Vitamin D supplementation, in fallers with vitamin D
insufficiency, has a significant beneficial effect on
functional performance, reaction time and
balance, but not muscle strength.
This suggests that vitamin D supplementation
improves neuromuscular or neuroprotective
function, which may in part explain the mechanism
whereby vitamin D reduces falls and fractures.
Oxford Journals, Medicine, Age and Ageing, Volume 33, Issue 6 pp. 589-595.
IV Congresso Nazionale AINAT
NAPOLI 17-18 dicembre 2010
Low Plasma 25-Hydroxyvitamin D and Calcium
Levels in Institutionalized Epileptic Subjects:
Associated Risk Factors, Consequences and
Response to Treatment with Vitamin D
M. W. J. DAVIE et al. Metabolic Unit, St. Mary's Hospital, Praed Street, London, UK.
108 subjects with a history of epilepsy
In a survey of
in a hospital for the mentally handicapped, administration of both phenobarbitone and
phenytoin was associated with low
serum calcium and plasma 25hydroxyvitamin D (25-(OH)D) levels in female subjects only.
Serum calcium levels in the other 108 subjects were lower in those experiencing the most
frequent fits, but serum calcium could not be restored to levels found in subjects not
receiving anticonvulsant drugs unless supraphysiological doses of vitamin D were given.
Vitamin D deficiency in the epileptic population receiving drugs was assessed by the
response of alkaline phosphatase to vitamin D administration.
A consistent fall of serum alkaline phosphatase was found only if the initial level exceeded
175 per cent of the normal value established by reference to a population not receiving
phenobarbitone or phenytoin. By this criterion five out of 45 subjects (11 per cent), aged
nine to 36 years were vitamin D deficient.
QJM: An International Journal of Medicine, Volume 52, Issue 1, 79-91
IV Congresso Nazionale AINAT
NAPOLI 17-18 dicembre 2010
Serum 25-Hydroxyvitamin D and
Depressive Symptoms in Older
Women and Men
Yuri Milaneschi et al. Longitudinal Studies Section,
Clinical Research Branch, National Institute on Aging, Baltimore, Maryland, USA.
Context
Hypovitaminosis D and depressive symptoms are common conditions in older adults.
Objective
We examined the relationship between 25-hydroxyvitamin D [25(OH)D] and depressive
symptoms over a 6-yr follow-up in a sample of older adults.
Design and Setting
This research is part of a population-based cohort study (InCHIANTI Study) in Tuscany, Italy.
Participants
A total of 531 women and
423 men aged 65 yr and older participated.
Main Outcome Measure
Serum 25(OH)D was measured at baseline. Depressive symptoms were assessed at baseline
and at 3- and 6-yr follow-ups using the Center for Epidemiological Studies-Depression Scale
(CES-D). Depressed mood was defined as CES-D of 16 or higher. Analyses were stratified by
sex and adjusted for relevant biomarkers and variables related to sociodemographics,
somatic health, and functional status.
The Journal of Clinical Endocrinology & Metabolism 2010 Vol. 95, No. 7 3225-3233
IV Congresso Nazionale AINAT
NAPOLI 17-18 dicembre 2010
Serum 25-Hydroxyvitamin D
and Depressive Symptoms
in Older Women and Men
Yuri Milaneschi et al. Longitudinal Studies Section,
Clinical Research Branch, National Institute on Aging, Baltimore, Maryland, USA
Results
Women with 25(OH)D less than 50 nmol/liter compared with those with higher levels
experienced increases in CES-D scores of 2.1 (P = 0.02) and 2.2 (P = 0.04) points higher at,
respectively, 3- and 6-yr follow-up. Women with low vitamin D (Vit-D) had also significantly
higher risk of developing depressive mood over the follow-up (hazard ratio = 2.0; 95%
confidence interval = 1.2–3.2; P = 0.005). In parallel models, men with 25(OH)D less than 50
nmol/liter compared with those with higher levels experienced increases in CES-D scores of
1.9 (P = 0.01) and 1.1 (P = 0.20) points higher at 3- and 6-yr follow-up. Men with low Vit- D
tended to have higher risk of developing depressed mood (hazard ratio = 1.6; 95% confidence
interval = 0.9–2.8; P = 0.1).
Conclusion
Our findings suggest that hypovitaminosis D is a risk
factor for the development
of depressive symptoms in older persons. The strength of the prospective
association is higher in women than in men. Understanding the potential causal pathway
between Vit- D deficiency and depression requires further research.
The Journal of Clinical Endocrinology & Metabolism 2010 Vol. 95, No. 7 3225-3233
IV Congresso Nazionale AINAT
NAPOLI 17-18 dicembre 2010
Vitamin D controls T cell antigen receptor
signaling and activation of human T cells
Phospholipase C (PLC) isozymes are key signaling proteins downstream of
many extracellular stimuli. Here we show that naive human T cells had very low expression of
PLC-γ1 and that this correlated with low T cell antigen receptor (TCR)
responsiveness in naive T cells. However, TCR riggering led to an upregulation of ~75-fold in
PLC-γ1 expression, which correlated with greater TCR responsiveness.
Induction of PLC-γ1 was dependent
on vitamin D and expression of the
vitamin D receptor (VDR).
Naive T cells did not express VDR, but VDR expression was induced by TCR signaling via the
alternative mitogen-activated protein kinase p38 pathway. Thus, initial TCR signaling via p38
leads to successive induction of VDR and PLC-γ1, which are required for subsequent
classical TCR signaling and T cell activation.
Marina Rode von Essen et al. Nature Immunology 2010, 11, 344 - 349
IV Congresso Nazionale AINAT
NAPOLI 17-18 dicembre 2010
Vitamin D, a neuro-immunomodulator: implications
for neurodegenerative and autoimmune diseases.
Fernandes de Abreu DA et al. Institut Jean Roche, Université Aix-Marseille, France.
It has been known for more than 20 years that vitamin D exerts marked effects on immune
and neural cells. These non-classical actions of vitamin D have recently gained a
renewed attention since it has been shown that diminished levels of vitamin D induce
immune-mediated symptoms in animal models of autoimmune diseases and is a risk
factor for various brain diseases.
For example, it has been demonstrated that vitamin D:
(i) modulates the production of several neurotrophins,
(ii) up-regulates Interleukin-4
(iii) inhibits the differentiation and survival of dendritic cells,
resulting in impaired allo-reactive T cell activation.
Not surprisingly, vitamin D has been found to be a strong candidate risk-
Multiple Sclerosis (MS)
modifying factor for
, the most
prevalent neurological and inflammatory disease in the young adult
population. Vitamin D is a steroid hormone, produced photochemically in
the animal epidermis.
Psychoneuroendocrinology. 2009 Dec;34 Suppl 1:S265-77
IV Congresso Nazionale AINAT
NAPOLI 17-18 dicembre 2010
Vitamin D, a neuro-immunomodulator: implications
for neurodegenerative and autoimmune diseases.
Fernandes de Abreu DA et al. Institut Jean Roche, Université Aix-Marseille, France.
Vitamin D acts through
two types of receptors:
1. the vitamin D receptor (VDR), a member of the steroid /
thyroid hormone superfamily of transcription factors
2. the MARRS (membrane associated, rapid response
steroid binding)
receptor, also known as Erp57/Grp58.
Was assessed how vitamin D imbalance may lay the foundation for a range
of adult disorders, including brain pathologies
(Parkinson's disease, epilepsy, depression)
and immune-mediated
disorders
(rheumatoid arthritis, type I diabetes mellitus, systemic
lupus erythematosus or inflammatory bowel diseases).
Psychoneuroendocrinology. 2009 Dec;34 Suppl 1:S265-77
IV Congresso Nazionale AINAT
NAPOLI 17-18 dicembre 2010
Vitamina D nelle giovani: migliora forza muscolare e riduce l’obesità
V. Gilsanz et al. Vitamin D Status and Its Relation to Muscle Mass and Muscle Fat in
Young Women. Journal of Clinical Endocrinology & Metabolism, 2010
La vitamina D svolge un ruolo importante nella patogenesi delle malattie
autioimmuni e dell’ipertensione arteriosa.
Townsend Jonathan V. Wright. Vitamin D: its role in autoimmune disease and hypertension.
Letter for Doctors and Patients. FindArticles.com. 21 Nov, 2010.
La vitamina D aumenta la libido maschile
Wehr E, Pilz S, Boehm BO, März W, Obermayer-Pietsch B. Association of
vitamin D status with serum androgen levels in men. Clin Endocrinol (Oxf).
2009 Dec 29.
La vitamina D contrasta i tumori del colon.
Silvia Olvarez-Díaz et al. Cystatin D is a candidate tumor suppressor gene induced
by vitamin D in human colon cancer cells. J Clin Invest. 2009; 119(8):23 – 43.
IV Congresso Nazionale AINAT
NAPOLI 17-18 dicembre 2010
La vitamina D in allattamento è indispensabile per
madre e bambino
Good Mojab, C. Mental Health Care for Breastfeeding Mothers with Postpartum
Depression. Hillsboro, OR: LifeCircle Counseling and Consulting, LLC 2006.
Alleviation of migraine with therapeutic Vit.D and calcium
Susan Thys-Jacobs, Headache 2005
Vit. D and calcium in menstrual migraine
Susan Thys-Jacobs, Headache 2005
Vitamin D Deficiency and Chronic Low Back Pain in Saudi
Arabia Saud Al Faraj, MD*, and Khalaf Al Mutairi
SPINE 28 (2) 177–179, 2003
IV Congresso Nazionale AINAT
NAPOLI 17-18 dicembre 2010
Carenza di vitamina D….
.. . è tutta colpa dei geni
fattori genetici
Oltre all’esposizione al sole e la dieta alcuni
hanno
un ruolo nel rischio di sviluppare un'insufficienza di vitamina D.
Tre siti genetici sono funzionalmente legati alle concentrazioni di vitamina D.
Analizzando i livelli di vitamina D nel siero del sangue di quasi
34.000 persone di discendenza europea, i ricercatori
hanno identificato i tre siti genetici (loci) coinvolti:
1. nella sintesi del colesterolo,
2. nel metabolismo della vitamina D,
3. nel trasporto della vit D.
I soggetti che mostravano varianti genetiche nocive (alleli) in tutti questi
luoghi contemporaneamente avevano 2,5 probabilità in più di avere
concentrazioni di vitamina D più basse di 75 nanomoli per litro
(nmol/L).
Wang, TJ et al. Common genetic determinants of vitamin D
insufficiency: a genome-wide association study. The Lancet, 2010
IV Congresso Nazionale AINAT
NAPOLI 17-18 dicembre 2010
Vitamin D, nervous system and aging
.
Tuohimaa P et al. Medical School, University of Tampere, 33014 Tampere, Finland.
Low serum calcidiol concentrations are associated with an
increased risk of several chronic diseases including
osteoporosis, cancer, diabetes, autoimmune disorders,
hypertension, atherosclerosis and muscle weakness
all of which can be considered aging-related diseases.
The relationship of many of these diseases and aging-related changes in physiology
show a U-shaped response curve to serum calcidiol concentrations.
Clinical data suggest that vitamin D(3) insufficiency is associated
with an increased risk of several CNS diseases, including:
Alzheimer's and Parkinson's disease, multiple sclerosis, seasonal
affective disorder and schizophrenia.
In line with this, recent animal and human studies suggest that vitamin D insufficiency
is associated with abnormal development and functioning of the CNS.
Overall, imbalances in the calcipherol system appear to cause abnormal function,
including premature aging, of the CNS.
Psychoneuroendocrinology. 2009 Dec;34 Suppl 1:S278-86.
IV Congresso Nazionale AINAT
NAPOLI 17-18 dicembre 2010
…chisto è ‘o paese do sole. . .
…chisto è ‘o paese do mare. . .
Grazie per l’attenzione!
www.salus.it / neurologia