Vitamin D Deficiency: A Predictor of Stroke Risk Pamela Barainca, RD, LDN, CNSC Clinical Nutrition Manager Shady Grove Adventist Hospital
Objectives Attendees will understand: The roles of Vitamin D as it relates to stroke Factors that increase the risk of insufficiency and deficiency of Vitamin D Measuring, maintaining and repleting Vitamin D levels if needed
Fast Facts from the Centers for Disease Control Coronary heart disease is leading cause of death, stroke is third, and is the leading cause of disability in industrialized nations.
Fast Facts from the Centers for Disease Control ~795,000 strokes occur in the United States each year, 77% of these are first or new strokes. Roughly three-quarters of all strokes occur in people aged 65 years or older. In 2007, a total of 135,952 people died from stroke in the United States. Highest risk factor for stroke is HTN http://www.cdc.gov/features/stroke/ Accessed 4.16.2012
High Blood Pressure Vit D impacts renin-angiotension system to decrease blood pressure Data from NHANES 1988-1992 found only 8% of Blacks had sufficient 25,OHD Judd SE, Zeigler TR, Wilson PWF, Tangpricha V. Optimal vitamin D status attenuates the age-associated increase in systolic blood pressure in white americans: results from the third National Health and Nutrition Examination Survey. Am J Clin Nutr. 2008;87:136-41
Interpreting 25(OH) Vitamin D Levels Excess: >200 ng/ml >500 nmol/l Adequate: 31-60 ng/ml 77.5-150 nmol/l Potentially Toxic Too much calcium and phosphorus in blood Insufficient: 21-30 ng/ml 52.5-75 nmol/l Deficient: <20 ng/ml <50 nmol/l Inadequate (Severe Deficiency: <10 ng/l, <25 nmol/l)
What is the Relation of Vitamin D to Stroke? Do low Vitamin D levels predict a high risk for stroke? Inverse relationship?
German Cohort Study Prospective cohort study of 3316 white patients 1997-2000 Mean follow-up of 7.75 years Increased odds ratio of 82% of a fatal stroke in patients with lowest vitamin D levels. Study controlled for cardiovascular risk factors, age, gender, HTN, diabetes, physical activity, calcium and parathyroid hormone.
German Cohort Study, British Studies Authors conclusions: Vitamin D supplementation For patients with a high stroke risk is preventive Therapeutic after a stroke Pilz, Stefan MD; Dobnig, Harald MD; Fischer, Joachim E. MD; Wellnitz, Britta LLD; Seelhorst, Ursula MA; Boehm, Bernhard O. MD; Marz, Winfried MD. Low Vitamin D Levels Predict Stroke in Patients Referred to Coronary Angiography. Stroke. 39(9):2611-2613, September 2008. Poole, Kenneth E.S. BM, MRCP; Loveridge, Nigel PhD; Barker, Peter J. MSc; Halsall, David J. PhD, MRCPath; Rose, Collette; Reeve, Jonathan DM, BSc, FRCP; Warburton, Elizabeth A. MA, DM, MRCP. Reduced Vitamin D in Acute Stroke. Stroke. 37(1):243-245, January 2006.
Low Vitamin D & Stroke: National Health and Nutrition Examination Survey (NHANES) NHANES data demonstrates that >90% of Blacks, Hispanics and Asians and almost 75% of whites suffer from Vitamin D insufficiency. Near doubling of insufficiency of Vitamin D since previous NHANES study Low Vitamin D is directly associated with low bone density in the hip. Adams, J.S and Hewison, M. Update in Vitamin D. J Clin Endocrinol Metab 95:471-478, 2010.
NHANES III continued As Vitamin D levels decrease to <30 ng/ml, there is an increase in adjusted mortality from all causes. As Vitamin D drops, the incidence in cardiovascular disease, HTN, BMI and insulin resistance increases criteria for metabolic syndrome. The drop in Vitamin D is mirrored by the increase in obesity
How is Metabolic Syndrome Associated with Vitamin D Deficiency? 3 of the following must be present in diagnosis of Metabolic Syndrome: Abdominal obesity, high A1c, high blood pressure, high triglycerides and low HDL cholesterol 25,OHD is inversely related to: Blood pressure >140/90 mmhg Glucose > 125 mg/dl, insulin resistance BMI > 30 kg/m 2 Ford ES, McGuire LC, Ajani UA and LIU s. Concentrations fo Serum Vitamin D and the Metabolic Syndrome Among U.S. Adults. Diabetes Care.2005 May;Vol 28, No 5: 1128-1230
Journal Article in Stroke 2012: Ahead of Print Analysis of Nurses Health Study (NHS) 464 women who developed stroke and 464 matched healthy controls (121,700 RNs in study) 1.49 increased risk of stroke in lowest Vit D level compared to highest NHS + 6 prospective studies as meta analysis 1214 stroke pts Pooled relative risk of 1.59 for lowest Vit D level compared to highest for stroke Highest risk levels in RNs with diabetes and HTN Sun Q, Pan AP, Hu FB, Manson JE, Rexrode KM. 25-Hydroxyvitamin D and the Risk of Stroke. A Prospective Study and Meta-analysis. Stroke. 2012;43:00-00.
What is Vitamin D? AND A hormone (from Greek word meaning impetus") is a chemical messenger. A hormone is sent out into the blood and cells with the right receptors respond to the hormone at another site. Steroid hormone--binds and activates a receptor that regulates gene expression Seco-steroid hormone slight structural difference from a steroid hormone A cytokine. The main difference is that a cytokine causes a local effect. The cytokine effects are less well known and much research is going on in this area.
Examples of Vitamin D Receptor (VDR) Locations Skeletal Muscle Thyroid Brain GI: Duodenum, Jejunum, Colon Skin Pancreas Prostate Breast Macrophages, B cells, T cells Locations of VDR provide clues to disease states that are associated with Vit D deficiency
Vitamin D: the Seco-Steroid Hormone Well established role Calcium levels are tightly regulated in the blood Low calcium levels in the blood cause the parathyroid glands to secrete Parathyroid Hormone (PTH) Vitamin D is changed to its active form in the kidney Causes increased calcium and phosphorus absorption from the gut for bone mineralization Decreased calcium excretion in the urine Calcium is taken from the bones Recommended Daily Intake based on prevention of Rickets and Osteomalacia
Vitamin D Cytokine Roles Adaptive and Innate Immune systems Protection from microbial invaders via macrophages, and T and B lymphocytes Increases muscle strength, size and ability to contract Inhibits renin synthesis in the kidneys to decrease blood pressure >1000 genes with Vit D response elements Active form is made locally where it is needed If not enough Vit D, the active form is not made Heaney RP, Vieth R, Hollis BW. Vitamin D Efficacy and Safety. Arch Intern Med/vol 171 (no. 3) Feb 14, 2011:266.
Risk Factors for Vitamin D Deficiency Age: ability to make vitamin D from sun exposure decreases with increasing age Lack of sun exposure, sun block Immobility ability to get outside Geography Decreased intake of Vitamin D from fortified foods or supplements
Who is Most at Risk for Vit D Deficiency? Women more than men Blacks more than Mexican Americans more than Whites People with obesity
Primary Vit D Source: The Sun Sunlight: UVB wavelength-- No known cases of toxic Vit D synthesis from sun Excess pre-vitamin D is destroyed by sunlight Hathcock JN, Shoa A, Vieth R, Heaney R. Am J Clin Nutr. 2007;85:6-18.
Sunlight Young caucasian can produce 1000 IU of Vit D with 30 minutes of sun exposure to 10% of skin surface in Bay Area in the summer Dark complexion = SPF 15, blocks 99% of UVB rays Older people take 4-5 times as long to produce Vit D in the skin
Making Vit D from the Sun In Maryland, little Vit D 3 is produced in the skin from November through February with oblique angle of the sun. Time of day, season and altitude all matter Holick MF. Vitamin D Deficiency. NEJM. 2007;357:266-81.
Vit D Food Sources Food Fatty fish (salmon, sardines, tuna, cod liver oil) Liver Egg Yolks Shitake mushrooms Fortified: Milk/dairy: ALL milk is fortified, not just Vit D milk ~100 IU in 8 oz of milk nonfat, low fat AND whole milk Breakfast cereals, orange juice
Supplemental Vit D Sources D 2 : plant form, manufactured by irradiating ergosterol from yeast D 3 : Manufactured from irradiated 7- dehydrocholesterol from lanolin Half life of 4-6 weeks Now available OVC in 50,000 IU concerning! Large doses of Vitamin D are NOT recommended unless prescribed by your physician
Excessive Vit D Levels Toxic Vit D levels are associated with pain, conjunctivitis, anorexia, fever, chills, weight loss, thirst, vomiting, hypercalcemia and hypercalcuria Urine calcium, followed by serum calcium increases must be associated with hypercalcemia when 25,OHD exceeds ~150 ng/dl True toxicity can go unnoticed and calcifies internal organs especially the kidneys--rare
What Lab Should Your Physician Measure? 25(OH)Vit D NOT the active form: 1,25 (OH) Vit D
How Much Vit D to Consume? Need to know your lab levels if you are at risk for Vitamin D deficiency The goal is to have sufficent 25,(OH) Vitamin D in your blood for optimum health for your bones and for all the other Vitamin D functions
How Much Vitamin D Should You Take? If your lab Vit D levels are adequate, 1000-2000 IU per day to maintain Institute of Medicine recommends 800 IU/day of Vit D for people 71+ years. National Osteoporosis Foundation recommends an intake for adults age 50 and older of 800 1,000 IU of vitamin D 3 daily. If you are really deficient, the dose is 50,000 IU per week for 8 weeks, then re-check lab http://www.nof.org/aboutosteoporosis/prevention/calcium Accessed 4.17.12.
Low Bone Mineral Density in Stroke Survivors 4 reasons for low bone mineral density in Stroke survivors: Lack of limb use with paralysis Vit D deficiency: Diet Lack of sunlight Hyperparathyroidism Vit K deficiency Sato Y, Honda Y, Kuno H, Oizumi K. Menatetrenone Ameloirates Osteopenia in Disuse-Affected Limbs of Vitamin D and K Deficient Stroke Patients. Bone.Vol 23, no 3 September 1998; 291-296.
Stroke, Hip Fracture, and Vit D Osteopenia: common complication of stroke Greatest loss of bone first year after stroke, but loss continues without intervention Hip fracture after stroke affects 5-40% of stroke survivors Sato: deficient pts had 7x risk of hip fracture as controls of same age group. Osteomalacia likely muscle strength, increasing gait instability and frequent falls. Sato Y, Takeshi A, Kondo I and Satoh K. Vitamin D Deficiency and Risk of Hip Fractures Among Disabled Elderly Stroke Patients. Stroke. 2001;32:1673-1677.
Bone Density Osteoporosis: Type I, usually female, postmenopausal, affects trabecular bone, lumbar vertebrae, loss of estrogens or androgens Type II, affects men and women, >65 years, trabecular and cortical bone, hips and vertebrae, aging, loss of BMD Drugs e.g. steroids, anti-seizure, drugs that induce cholesterol malabsorption, HARRT Co-morbidities e.g. Cystic fibrosis, Celiac dx, Crohn s, colitis, lactose intolerance
Low Bone Density in the Hip Directly related to low blood (serum) Vitamin D levels Women s Health Initiative data: For every 10 ng/ml decrease in serum Vitamin D, there is a significant upward trend in the risk of hip fracture Double risk of hip fracture if vitamin D is deficient Adams and Hewison. Update in Vitamin D. J Clin Metab. February 2010, 95(2):471-478.
Calcium Absorption with Vitamin D Necessary to absorb calcium from intestine hormonal role Need 1,200-1500 mg/day of calcium Take maximum of 500-600 mg at one time. More won t be absorbed in a single dose. Food choices are preferred Supplements: Calcium carbonate or citrate. May take with magnesium if calcium is too constipating.
Fracture Protection 25,OHD <26 ng/ml, No fracture protection even when taking 800 IU Vit D/day. 800 IU of Vitamin D demonstrates 0-24% in bone fx. Many elderly require 4000 IU daily. Meta-analysis of 5 RCTs: Vit D supplementation the risk of falls in >20% of elderly community and institutionalized men and women. Takes 3 months of Vit D repletion to see full change in muscle mass Bischoff Ferrari et al. Effect of Vitamin D on Falls. JAMA. 2004;291:1999-2006.
Effectiveness of Vit D to Reduce Falls and Hip Fx After a Stroke 96 elderly women followed for 2 years after a stroke Pts randomly assigned to take 1000 IU Vit D (n= 48) daily or placebo (n=48) Baseline: all pts were deficient in Vit D
Results of Study Patients who took Vit D had a 59% reduction in falls compared to placebo Four hip fractures in placebo group, zero hip fractures in fortified group Improved muscle strength and increases in number and size of type II muscle fibers in supplemented group Sato Y, Iwamoto J, KanokoT, Satoh K. Low-Dose Vitamin D Prevents Muscular Atrophy and Reduces Falls and Hip Fractures in Women after Stroke: a Randomized Controlled Trial. Cerebrovasc Dis. 2005;20:187-192.
Vitamin D Supplementation and Total Mortality 2008 NHANES Study 25: OHD <17.8 ng/ml associated with 26% increased risk of mortality Melamed ML, Michos ED, Post W Astor B. 25-hydroxyl Vitamin D Levels and the Risk of Mortality in the General Population. Arch Intern Med.2008 August 11;168(15):1629-1637.
Summary Recommend checking your Vitamin D level if you are at high risk for deficiency For bone health, maintain a 25(OH)D level >34ng/L The goal is an adequate level of Vitamin D not too low, not too high.
Take Home Message Edward Giovannucci, MD, ScD of the Harvard School of Public Health in Archives of Internal Medicine regarding Vit D writes: a more proactive attitude to identify, prevent and treat vitamin D deficiency should be part of standard medical care. Thank you!