Vitamin Deficiency in the Elderly by Zoe Salgado Family Medicine Residency Program.

Vitamin Deficiency in the Elderly

by Zoe SalgadoFamily Medicine Residency Program

Vitamins

Definition: Chemically unrelated organic

compounds that are essential for normal metabolism

Cannot be synthesized, therefore must be ingested

Different from minerals (Ca, Fe) or food supplements (Herbs)

Vitamins Vitamin A, D, E, K Vitamin C and the

B vitamins B1-Thiamine Riboflavin B3-Niacin Pantothenic acid Biotin B6-pyridoxine B12 folate

Vitamin deficiency

Gross deficiencies are recognized by clinical syndromes

Are seen in poorer areas Seen in Western societies in special

populations Elderly, vegans, new immigrants, the

very poor, alcoholism, malabsorption (hx gastric bypass), parenteral nutrition

Daily values

Daily values=DV, prior known as RDA established by the National Research

Council and National Academy of Sciences may not be sufficient for chronic disease normal values in general are uncertain many people have suboptimal levels

Question Can optimizing vitamin intake prevent

chronic disease? some biochemical abnormalities can improve

with intake, then reach a plateau causing no further improvement >>suggests a correctable metabolic disease Eg:

1.homocysteine levels increase as folic acid decreases

2. Methylmalonic acid levels increases with low B12

3. PTH rises with low Vitamin D

Overview Vitamin D---DV 400IU Vitamin B12—DV 6 mcg Folic Acid---400mcg

Vitamin A First fat soluble vitamin to be discovered Part of compounds called retinoids Essential for vision, immune response,

epithelial growth and repair Can store 1 year of reserve RBP=retinol binding protein-bonds to

Vitamin A in blood

Requirements Males > 10 yo need 1000mcg Females > 10yo need 800 mcg only 40-60% plant bioavailability vs

80-90% of animal protein Zinc and/or Iron deficiency can

interfere with metabolism LABS

-RBP, CBC, serum retinol(costly)

Vitamin A deficiency Complications

Dry skin, dry hair, broken nails-may be first sign

Night blindness Xeropthalmia-no tears-predisposes to

blindness Hyperkeratosis-goose bump skin

Vitamin K(VK) Found in green, leafy vegetables

and oils Plays a role in coagulation cascade Body’s reserve lasts one week 85% absorbed in terminal ileum

Vitamin K deficiency Def due to

chronic illness, multiple abdominal surgeries, liver or biliary disease, alcoholism, drugs: Abics(cephalos) Coumadin, salicylates, sulfa

Clinical Manifestations Bleeding, hematoma, ecchymosis

Vitamin K deficiency Labs:

Pt/Ptt Vit K level (0.2-1 ng/ml)

RX Replace Vit K IM( 10 mg/d) , SQ, or PO

(5-20 mg) FFP( begin- 2 Units)

Vitamin D Few foods contain Vit D (fatty fish

and eggs) Dermal synthesis or fortified foods

(milk) are the main source Two forms of Vitamin D-

Ergocalciferol -Vit D2 Cholecalciferol-Vit D3

Vitamin D Metabolsim Vitamin D3 is synthesized in the skin

during UV light exposure Vit D3 from skin or diet is then

hydroxylated in the liver, then kidneys to active form Vit D dihydrohycholecalciferol (calcitriol)

Vitamin D Deficiency Causes

Decreased sun exposureIn Boston and Edmonton Vit D cutaneous production ceases in winter (1)

Low dietary intake/absorption• Half of elderly women take in less than 65 units/day• Achlorydia-common in elderly, decreases vitamin

absorption• NOT common in IBD (including Chron's) per AGA

guidelines

1-Tangpricha, 2002

Prevalence

MSK pain (unrecognized !!!!!!) Hospitalized pts Women being treated for OP CKD (usually 1,25DOH but also 25OHD GI malabsorption Gastric bypass Cystic fibrosis Extensive burns

Vitamin D deficiency Independent predictors

Low Vitamin D intake Winter Housebound status

Who should be tested? Institutionalized or home bound Suspected malabsorption Evaluation of osteoporosis

Vitamin D Deficiency and Bone health Osteoporosis

Postmenopausal women with low 25 OHD levels have lower bone densities (3)

Falls Meta analysis of 5 RCT with 1237 older patients, Vit D

use reduced falls by 22% compared to Calcium or placebo (4)

One RCT of nursing home residents found 50% fall reduction over 5 months with Vit D 800 IU BUT not at lower doses(5)

• 3-Villareal, 1991, 4-Bischoff-Ferrari, 2004, 5-Broe, 2007

Vitamin D deficiency and cancer High levels of Vitamin D may decrease

cancer risk One 4year RCT compared Ca(1400-

1500mg) alone, Ca + Vit D (1100IU/d) or placebo in 1179 women > 55yo (2) Results: both Ca and Ca/Vit D appear to

decrease the risk of incident cancer ( after 1 year RR 0.23, 95% CI)

Other RCT using different doses of Vit D have not found risk reduction

• 2-Lappe,2007

Vitamin D serum levels Test to order: serum 25 OH Vit D

(calcidiol) Normal cluster 30-32 ng/ml(75-

80mmol/L) “levels of 28-40 may lower the

fracture risk” No consensus on optimal 25OH

concentration for skeletal health

Vitamin D serum levels Different definitions of deficiency Option #1

Vit D Insufficiency= 20-30ng/ml Vit D Deficiency=< 20 ng/ml

Option #2 Vit D deficiency 9-28 Severe deficiency 8 or less

Optimal intake 1997 national academy of sciences

recommendation: 400IU/d age 51-70 600 IU/d age > 71 However more recent data shows avg

adult needs 800-1000IU/d to maintain level of 30

Older persons confined indoors may have low levels even at this intake

Vitamin D levels in NHCU Total patients in NHCU=85 # of patients tested 23 Moderate deficiency= 16 Severe deficiency (levels at 8 or less)=3 Normal=4 82% of those tested had moderate

deficiency, 13% had severe deficiency

25 OHD LEVELS OVER TIME IN NHCU

25 OHD LEVELS TESTED IN 23 PATIENTS March 2008

Vitamin D in NHCU

Of those tested: Dx of falls=3…..(all had moderate

deficiency) Dx of fx= 5…..(4 had deficiency, one

with severe deficiency) Dx MSK pain=4.….(3 with moderate

deficiency, 1 with severe) Dx of OP=2…..(1 with deficiency, 1

normal)

NHCU Vitamin D Data 1 1 patient with no MSK hx at all had

Vit D level of 6 The highest Vit D level of 61, pt had

hx of osteopenia # of patients with continued current

deficiency =14, of those only 7 were being treated

Current Recommendations

Do NOT screen (Grade 2C), but give supplementation below(Grade 2B)

Daily 800 IU at least and 1.2 g of elemental calcium

Lower intake-not as effective Higher intake( safe upper limit

2000IU/day)-hypercalcemia DO NOT recommend switching from daily

800IU to high dose intermittent (100,000 units q 4 months) unless pt is noncompliant

Vitamin D supplementation For every 40 IU of D3 given, serum 25-

OH D increased by 0.3-0.4 ng/ml Rx for deficiency

PO: 50,000 units of D3 q week x 6-8 weeks, then 800-1000 IU daily

IM : D3 (300,000 IU) in 1 or 2 doses per year Rx for Insufficiency

800-1000 IU of D3 daily( will bring avg adult to serum level of 30 in 3 months)

Measure serum levels after 3 months of starting rx

Vitamin B12 Deficiency causes:

Neurologic disease Megaloblastic anemia, pernicious anemia May be important cause of

hyperhomocysteinemia (CV disease, OP) Subtle deficiency even without anemia

may cause dementia and ?balance problems

TABLE 1 Clinical Manifestations of Vitamin B12 Deficiency

Hematologic Megaloblastic anemia Pancytopenia (leukopenia, thrombocytopenia) Neurologic Paresthesias Peripheral neuropathy Combined systems disease (demyelination of dorsal columns and corticospinal tract) Psychiatric Irritability, personality change Mild memory impairment, dementia Depression Psychosis Cardiovascular Possible increased risk of myocardial infarction and stroke

Suboptimal B-12 deficiency

Caused by poor absorption and inadequate intake

Malabsorption-cobalamin unable to release from dietary proteins esp with low gastric acid secretions

Alcoholism

B12 level

Normal-> 300 pg/ml cobalamin deficiency unlikely

Borderline 200-300-deficiency possible

Low < 200 -deficiency

B 12 deficiency Pts with low normal or even normal

B12 levels may be deficient Homocysteine (HC) and

methylmalonic acid(MMA) levels will be high with deficiency

B12 deficiency

If deficiency measured by methylmalonic acid levels rising with low intake and falling with supplementation, there may be deficiency with even normal levels

One study showed 82% deficiency in 282 elderly patients

Monitoring B 12 deficiency If folate> 4 ng/ml and cobalamin

>300pg/ml, deficiencies unlikely, no further testing

If either of above levels are low, check methylmalonic acid and total homocysteine levels If both normal>no deficiency If both are high>clear B12 deficiency If MMA is normal and HC is high, folate

deficiency (sens 86%, spec99%)

B12 LEVELS IN NHCU

TOTAL PATIENTS=85 TOTAL TESTED=73 DEFICIENCY=0 BORDERLINE=7 NORMAL/HIGH=66

OF 73 TESTED PATIENTS, 66 HAD NEUROPSYCHIATRIC DIAGNOSIS

9% PATIENTS TESTED HAD BORDERLINE DEFICIENCY

B 12 LEVELS OVER TIME NHCU

Recommendations for B12 supplementation Older adults - 6mcg daily Vitamin supplements have 100 mcg/dose May be inadequate dose in:

Elderly Atrophic gastritis Vegans Gastric bypass sx Alcoholics Poor dietary intake

Dosing of B12 Few studies to guide dosing If pernicious Anemia dose of IM B12 is 100

-2000mcg/day (no toxicity at higher doses)

One RCT suggests dosing at higher than 50mcg/day may be needed to normalize B12 (no known toxicity at this level)

In high risk pts-recommendation to have periodic monitoring of either methylmalonic acid or B12 level

Folic acid Found in green leafy vegetables,

fruits, cereals, nuts, mats Folic acid (the supplement form) has

same effect but more bioavailable than folate

Deficiency leads to megaloblastic anemia

Folic Acid in Pregnancy Decreases risk of neural tube defect

Appears dose dependent - In one study

400 mcg decreased rate of NTD by 57%5000mcg decreased rate by 85%

Folic acid in Cardiovascular Disease Elevated homocysteine associated

with increased risk of CV disease Folic acid, B6, B12 can decrease

homocysteine However RCTs of supplementations

for secondary prevention do NOT support a beneficial effect of vitamins in CV disease

Folic acid and cancer A functional polymorphism in MTHFR(major

enzyme in folate metabolism) linked to colorectal cancer, >>Folate may protect DNA against damage during cell division

One RCT -1 g of folic acid vs placebo in 1021 pts with

colorectal adenoma found no difference in the risk of new adenoma at 3 years RR 1.04, 95%CI but found high risk of advanced lesions at 3 years

At 6 years f/o with colonscopy 607 pts results were repeated

Recommendations for folate supplementation Do NOT take folic acid for reducing

cancer risk Evidence unclear and limited

regarding association between hypertension and hearing loss

Toxicity Water soluble vitamins

toxic at thousands x the DV Vitamin C-increased risk of kidney stones-

controversial Fat soluble vitamins

Vit D- hypercalcemia at dose of 2000IU/d Vitamin A –pregnancy-teratogenic Vitamin E- above 400 IU may be associated

with all cause mortality

Toxicity Vitamin A -HA, dizziness, blurred vision,

clumsiness, birth defects, Vitamin D-Constipation, weakness, anorexia,

weight loss, confusion B3-Niacin-Flushing, redness of skin, B6-pyridoxine-Numbness, paresthesia, ataxia Vitamin C-kidney stones Folate-can mask B12 deficiency

1. Tangpricha, V et al, Am J Med 2002, June 1:112(8)659-62

2.Lappe,LM, et al, Am J Clin Nut, Jun 85(6) 1586-91

3. Villareal, Dt,et al, J Clin Endocrinol Metab, 991, Mar ;72 (3) : 628-34

4.Bischoff-Ferrari, Ha, et al, JAMA, 2004, April 28;291(16):1999-2006

5. Broe, KE, et al, J Am Geriatr Soc 2007 Feb;55(2)234-9