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Vitamin D deficiency the cause of everything by muq18838


									                                                                 Health problems linked
                                                                 to vitamin D deficiency:

      Vitamin D deficiency:                    Type 1 and 2 diabetes
                                               Multiple sclerosis
                                                                             Cancers: breast, prostate,
                                                                             colon, pancreas, ovary,
    the cause of everything?                   Rheumatoid arthritis          Non-Hodgkin's lymphoma
             Louise Gagné M.D.                                               Myocardial infarction
                                               Periodontal disease
Family Physician Saskatoon Community Clinic    Increased susceptibility to   Stroke, congestive heart
         Clinical Assistant Professor          infection                     failure
                                                                             Wheezing in childhood
      Department of Community Health           Osteoporosis
                                               Low birth weight infants      Falls in the elderly
              and Epidemiology                                               Muscle strength in the
                                               Low seizure threshold
        University of Saskatchewan                                           elderly

                                                            A call to action:
  Current DRI’s for vitamin D
                                              “We call for international agencies such as
Birth to age 50: 200 IU                         the Food and Nutrition Board and the
Age 51-70:          400 IU                      European Commission’s Health and
Over age 70:        600 IU                      Consumer Protection Directorate-
Institutionalized &                             General to reassess as a matter of high
homebound:          800 IU                      priority their dietary recommendations for
                                                vitamin D, because the formal nationwide
UL (upper limit): 2000 IU
                                                advice from health agencies needs to be
     Vitamin D intakes in USA:
                                                          Sources of vitamin D
       food and supplements
 Children age 1-8 and                              UVB exposure
 Caucasian males age 9-50                          Foods: Fatty fish,
 had the best intakes (75%                         mushrooms, egg yolks
 ≥ DRI)                                            Fortified foods: milk,
 Vitamin D intakes were                            breakfast cereals,
 significantly lower in                            soymilk, butter
 females and African                               Supplements: fish liver
 Americans                                         oils, multivitamins,
                                                                             Cantharellus cibarius
                                                   vitamin D                   (Chanterelles)
 Older adults (50+) had the
 lowest intakes (30% ≥ DRI)

   UVB: Check your shadow

  ‘Vitamin D winter’                                 Who is at
  begins when your                                 increased risk
shadow, even at high
 noon, is longer than
                                                    of vitamin D
       you are                                       deficiency?

                                 Obese people are
                                  more likely to be
                                     vitamin D
                               deficient and vitamin
                                D deficiency seems
                               to predispose people
                                     to obesity

                 The elderly             Darker skin types
                                Melanin is an
People aged 62-80               excellent sunscreen
synthesize one third the
amount of vitamin D as a        On average, African
person aged 22-30 after         Americans have
the same sun exposure           levels of 25(OH)D
                                that are half that of
                                Caucasian Americans
                                       Breast fed infants
 Complete clothing coverage

                              Vitamin D levels in
                              breast milk reflect
                                  adequacy of
                              vitamin D stores in
                                   the mother


Inflammatory bowel disease      Anticonvulsants- Dilantin, Phenobarbital
Celiac disease                  Bile acid sequestrants- Cholestyramine
Cystic fibrosis                 Cimetidine, Ranitidine
Pancreatic insufficiency        Corticosteroids
                                Calcium channel blockers
                                Mineral oil, Orlistat
       VDR polymorhphisms        Antarctic researchers

 ‘bb’ genotype: colon
 and prostate cancer
 ‘ff” genotype: Graves’
 disease and Hashimoto’s
 ‘SS’ genotype: RR of 3.2
 for breast cancer in
 Latina women

Emerging research on vitamin D   Vitamin D physiology

     Most vitamin D
   research has been
  based on laboratory
studies, animal studies
    and observational
     human studies.
                                               Steps 2 and 3: hydroxylation
                       step 1                Circulating vitamin D is
                                             extracted by hepatocytes
                                                25(OH)D (calcidiol)
UVB light converts 7-dehydrocholesterol in
the skin to previtamin D3 vitamin D3         In the kidney 25(OH)D
binds to DBP circulation                     1,25-dihydroxyvitamin D
                                             (calcitriol), the hormonally
Dietary vitamin D is primarily absorbed in   active form of vitamin D
the proximal small bowel lymphatics

     Extrarenal production of
          1,25(OH)2 D                            Vitamin D has many roles
Hormonally active
vitamin D is synthesized                     Calcium homeostasis
in many other body                           Cell growth, differentiation,
tissues: skin, colon,                        apoptosis
prostate, mammary                            Immune modulation
tissue, adrenal medulla,                     Antioxidant/anti-
brain, lymph nodes,                          inflammatory activity
placenta, endothelium,
  Vitamin D and calcium balance                                     Bone health, muscle
                                                                     strength, fractures
Falling plasma calcium causes                                             and falls
increased parathyroid hormone                 Hip fractures: decreased by 26% (700-800 IU)
which increases production of
1,25(OH)2D in the kidney                      Optimal fracture prevention at ~100 nmol/l
                                              Bone density is higher in each subgroup of serum
Vitamin D is necessary for active             25(OH)D from 22.5-94 nmol/l
transport of calcium through the
intestinal mucosa                             Muscle strength: walking, sit to stand, improvement
                                              continued up to 94 nmol/l
Level of 25(OH)D for optimal
                                              Falls in the elderly: decreased by 46% with 700IU
calcium absorption is ≥ 80 nmol/l             vitamin D + 500mg calcium

                   Vitamin D and
                   osteoarthritis                                Cancer protection
 Vitamin D stimulates the synthesis of         Total cancer risk varies directly with
 proteoglycans by mature chondrocytes          latitude and with serum 25(OH)D
 Dietary intake of vitamin D in OA patients    Cellular effects of VDR signaling include
 has been found to be 80% below RDI            growth arrest, differentiation and/or
 Framingham Study: risk of OA progression      induction of apoptosis.
 was 3x higher in middle/low groups for        Vitamin D also inhibits angiogenesis and
 vitamin D intake and serum vitamin D          stimulates adherence of cells
                    Vitamin D and
                    breast cancer                                         Vitamin D and
                                                                          colon cancer
9/13 studies show less sunlight and/or less vitamin
D increases breast cancer risk
Women in lowest quartile of vitamin D had 5x          Colon cancer death rates are higher
higher breast cancer than women in highest            in areas with low solar radiation
                                                      Intakes ≥ 1000 IU/day or serum level
In breast tissue, the VDR functions to oppose
estrogen driven proliferation and maintain
                                                      ≥ 82 nmol/l have 50% lower risk

                                                                        Vitamin D and
                        Vitamin D and
                                                                       type II diabetes
                       prostate cancer
                                                      Vitamin D is necessary for insulin secretion
 Sunlight exposure= lower risk                           insulin resistance and insulin secretion
 Low 25(OH)D levels = higher risk                     are associated with low vitamin D
 Finland: Men below the median 25(OH)D had a          D deficiency-animal studies: 1st phase, then
 1.7x higher risk compared to men with levels         second phase insulin secretion impaired,
 above the median. These men also got prostate        then severe failure of insulin secretion
 cancer at a younger age and had more
 aggressive disease.                                  Nurses Health Study 800 IU/d 23% lower
                                                      risk of developing type II diabetes
                     Vitamin D and
                     heart disease                                Vitamin D and
                                                                  mood disorders
 Vitamin D deficiency is associated with an
 increased risk of:                           25(OH)D and 1,25 (OH)2D are lower in
    hypertension                              depression and schizophrenia
                                              Vitamin D increases “winter well being”
    myocardial infarction
                                              Vitamin D deficiency is associated with low
    heart failure
                                              mood and worse cognitive performance in
 Anti-inflammatory effects may play a role    older adults

 Vitamin D and type I diabetes                                  Multiple sclerosis

Large, well designed                          1,25(OH)2D3 can completely prevent EAE
prospective study of >12,000                  (autoimmune encephalitis) in mice
children followed for 30 years                More common in populations with low
Children given 2000 IU/day                    concentrations of vitamin D or low UV
vitamin D had a RR of 0.22                    exposure (higher latitudes)
Children with possible rickets                Nurses Health Study: highest vitamin D
had a RR of 3.0                               intake (≥ 400 IU) had 40% risk of M.S.
                                              JAMA: Healthy young adults with highest
                                              25(OH) D had a 62% reduction in MS risk
                                             Symptoms & signs of vitamin D
                    Vitamin D                        deficiency
                    deficiency              Mild/moderate may be
Definition is controversial. Reference      Diffuse
ranges and measurement methods vary         musculoskeletal pain
from lab to lab                             Deep bone pain,
#1 Deficiency is the level at which index   fractures
diseases such as rickets and osteomalacia   Proximal weakness,
appear                                      instability, difficulty with
                                            gait, climbing stairs
#2 Deficiency is when the PTH level
                                            Rickets, osteomalacia
begins to rise to maintain serum calcium

  Vitamin D deficiency: 25(OH)D
                                             Optimum levels of 25(OH)D for
Deficient < 25                               prevention of chronic disease
Relative insufficiency                      Based on the
25-70 nmol/L                                available evidence,
Optimal 70-250                              25(OH)D level
nmol/L                                      should be at least
Toxic > 250 nmol/L                          75 nmol/L (30 ng/ml)
       25(OH)D levels in Saskatoon,
      80                                             Higher dose therapy to correct
nmol/l 60                                  Lowest    deficiency
      40                                             Follow with maintenance dose
                                                     Oral vitamin D3 (cholecalciferol) is
                                                     treatment of choice in most patients
            Jan Mar May Jul Sep Nov                  To correct deficiency: D3 4000 IU/day
            Feb Apr June Aug Oct Dec                 with meals


  Liver or kidney problems
  Primary hyperparathyroidism
  Thiazides                                          There are widespread health benefits to
  History of kidney stones                           maintaining an optimum vitamin D intake
                                                     throughout life.
  Any condition where there is a risk of
  hypercalcemia (metastatic cancer)                  Consider annual screening, particularly
                                                     for those at increased risk of deficiency

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