D-mystifying Vitamin D

Lucia M. Novak, MSN, ANP-BC, BC-ADMThe Diabetes Institute

Walter Reed Army Medical Center, Washington, DC

Adjunct Assistant Professor, Graduate School of Nursing, Uniformed Services University of the Health Sciences, Bethesda,

MD

Hormone or Vitamin?

Hormone:› from Greek

“impetus”› is a chemical

released by a cell in one part of an organism, that sends out messages that affect cells in other parts of the organism

Vitamin:› essential organic

micronutrient that can only be obtained from an external source, food

25(OH)D or calcidiol› Inactive form› 2-3 week ½-life › Major circulating

form of Vitamin D› best indicator of

status

1,25(OH)2D or calcitriol› Active form› 4 hour ½-life› Regulated by serum

levels of PTH, Ca, PO4

› Levels normal or elevated in 2’hyperPTH

› Does not reflect Vitamin D stores

Measurement of Vitamin D

Vitamin D status by blood levels of 25(OH)D

Vitamin D status 25(OH)D ng/mL

Sufficient ≥ 30

Insufficient 20 to 29

Optimal 30-60

Side effects 88 Moyad, MA. (2008). Vitamin d: a rapid review. Urol Nurs, Oct 28(5), 343-349.

Potentially harmful/ intoxication

>150

Holick MF. (2007). Vitamin d deficiency. NEJM, 357(3), 266–80.

Prevalence of Vitamin D Deficiency in US:

Adults: INSUFFICIENT/DEFICIENT:

11-50% of healthy adults Age, season, location

Peds/Adolescents:› INSUFFICIENT: 61%› DEFICIENT: 9% Kumar, et al. (2009). Prevalence and Associations of 25-

Hydroxyvitamin D Deficiency in US Children: NHANES 2001-2004Pediatrics, 124(3), 362-370.

Tangpricha, V. et al. (2002). Vitamin d insufficiency among free-living healthy young adults. Am J Med., 112(8), 659-62.

Known Consequences of Vitamin D deficiency

Reduces intestinal absorption of calcium and phosphorus; increases PTH

Secondary Hyperparathyroidism: mineralization defect

Osteopenia/Osteoporosis Low skeletal calcium

Rickets/Osteomalacia Low phosphorus

Muscle weakness Standing/walking/falls

Associated Consequences of Vitamin D deficiency

› Cancer› CV disease› Diabetes› Autoimmune disorders› Infectious Diseases› more

Review available data:>1000 studies, 25 different health outcomes

IOM:› At least 14 scientists, broad range expertise› Assisted by experienced IOM staff members› Public input

Endo Soc Task Force:› Dr Michael Holick, MD› 6 additional experts› 1 methodologist› Medical writer› Member review

The general conclusions are:

IOM Prevalence

OVERESTIMATED Potential harm from

overtreatment

ENDO SOC Prevalence

UNDERESTIMATED, everyone at risk

IOM report is a POPULATION model, not intended to direct treatment

Both agree that there is NOT ENOUGH DATA to support beyond BONE HEALTH

Over-

treating

?

Vitamin D as a Biomarker

Biomarker of EXPOSURE› Reflection of SUPPLY› use to evaluate INTAKE

Biomarker of EFFECT› Using level as CAUSE and/or PREDICTOR

for health outcomes

Problems Identified

Factors Affecting Vitamin D levels:› Diet intake (food/supplements)› Dose size/frequency› Sun exposure

Time of day, season, skin pigment, latitude, sunscreen use, clothing, pollution, cloud cover, altitude

› Adiposity› Ancestry, especially African

More Problems Identified

PTH is inconsistent marker› Affected by renal function, exercise level,

time of day, diet› No consensus of optimal level to reduce

PTH or to prevent rise The interrelation of Vitamin D &

calcium› Can we truly separate/differentiate?

Still more Problems Identified

Assay used› Different types of assays

Radioimmunoassay high-performance liquid chromatography liquid chromatography tandem mass

spectroscopy› What is being measured?› Results not standardized, different

parameters of “normal” 20-100 ng/mL

The Most Significant Problem Identified:

No systematic, evidenced-based process currently exists for determining 25(OH)D cut points that clearly define Vitamin D DEFICIENCY › Use of higher than appropriate cut points

will artificially increase the estimated prevalence of Vitamin D deficiency and increase the risk for harm.

Based on the available data …

Biomarker of effect:

Scientifically proven, cause-effect relationship:

SKELETAL HEALTH

Laboratory ranges for Vitamin D status (ng/mL)

INSTITUTE OF MEDICINE 2010 Sufficient: ~ 20

(97.5%) Insufficient: 12 - < 20 Deficient: < 12 SEs/toxicity/pot harm:

> 50 >30 is NOT

consistently associated with increased benefits

U-shaped curve

ENDOCRINE SOCIETY 2011 Sufficient: ≥ 30 Insufficient: 20-29 Deficient: <20 Optimal: 40-60

IOM RDA for normal, healthy people to maintain 20 ng/mL:

0-12 months: 400 IU 1 year -70 years: 600 IU >70 years: 800 IU Pregnant/breastfeeding: 600 IU

ENDO SOCSUGGESTED DA to maintain >30 ng/mL:

0-12 months: ≥400 IU 1-18 yrs: ≥ 600 IU (1000) ≥19 yrs: ≥ 1000 IU (1500-2000) Pregnant/breastfeeding: ≥ 1000 IU (≥

1500)

Selected food sources of vitamin DFood Sources Vitamin D (IU)

1 Egg 20

Salmon, 3.5 ounces 360 farmed1000 wild

Mackerel, 3.5 ounces 345

Tuna, canned, 3.5 ounces 200

Mushrooms, 100 gm 100

Milk, fortified, 8 ounces 100

Breakfast cereals, fortified, 1 serving 40–100

Orange juice, fortified, 8 ounces 100

Source: Office of Dietary Supplements, National Institutes of Health

Sun Exposure

Arms and legs for 5-30 minutes › Depends on time of day, season,

pigmentation, latitude 10 am – 3 pm Twice a week 20,000 IU Tanning beds SKIN CANCER RISK!

Daily Dosage (IU) Expected serum level increase after 3 months(ng/mL)

100 1

200 2

400 4

800 8

1,000 10

2,000 20

Supplementation

D3 preferred (chemically similar, more effective)

BUT D2 is acceptable Fat soluble, take with meal/snack containing

fat

Treatment for DEFICIENCYEndocrine Society, 2011

0-18 yrs› 2000 IU/day or 50K IU/week x 6 weeks

>18 yrs:› 6000 IU/day or 50K IU/week x 8 weeks

Obese, malabsorption, meds› 2-3x MORE› 4000-10,000 IU/day

Elderly Reduced sun exposure

› Darker Skin› Institutionalized/Homebound› Sunscreeen use

Breastfed infants Renal & Liver Disease GBP/malabsorption Drugs (PTN, phenobarb, glucocorticoids, etc) Overweight/obese

ALMOST EVERYONE SHOULD BE SCREENED!

Only Screen High Risk Populations

Both Agree…… Research is needed

Large-scale, RCT Health outcomes/related conditions Adverse effects/toxicity/safety Physiology and molecular pathways Synthesis of evidence and research

methodology Dose-response relationships Sun exposure Intake assessments (assays)

Until then …

Counsel patients› Not to self-treat› Take per your CLEAR instructions› Limited supplies, no automatic refills› Careful with calcium intake

Monitor› Labs periodically

After 6-8 weeks therapy Seasonal late fall/early winter