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

2. Vitamins Definition: Cannot be synthesized, therefore must be ingested
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)

3. Vitamins Vitamin A, D, E, K Vitamin C and the B vitamins B1-Thiamine
Riboflavin
B3-Niacin
Pantothenic acid
Biotin
B6-pyridoxine
B12
folate

4. 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

5. 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

6. 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

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

8. 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

9. 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)

10. 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

11. 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

12. Vitamin K deficiency Def due to Clinical Manifestations
chronic illness, multiple abdominal surgeries, liver or biliary disease, alcoholism, drugs: Abics(cephalos) Coumadin, salicylates, sulfa
Clinical Manifestations
Bleeding, hematoma, ecchymosis

13. Vitamin K deficiency Labs: RX Pt/Ptt Vit K level (0.2-1 ng/ml)
Replace Vit K IM( 10 mg/d) , SQ, or PO (5-20 mg)
FFP( begin- 2 Units)

14. 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

15. 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)

16. Vitamin D Deficiency Causes Decreased sun exposure 1-Tangpricha, 2002
In 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

17. 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

18. Vitamin D deficiency Independent predictors Who should be tested?
Low Vitamin D intake
Winter
Housebound status
Who should be tested?
Institutionalized or home bound
Suspected malabsorption
Evaluation of osteoporosis

19. 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

20. Vitamin D deficiency and cancer
High levels of Vitamin D may decrease cancer risk
One 4year RCT compared Ca( mg) 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

21. Vitamin D serum levels Test to order: serum 25 OH Vit D (calcidiol)
Normal cluster ng/ml(75-80mmol/L)
“levels of may lower the fracture risk”
No consensus on optimal 25OH concentration for skeletal health

22. 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

23. 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 IU/d to maintain level of 30
Older persons confined indoors may have low levels even at this intake

24. 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. 25 OHD LEVELS OVER TIME IN NHCU
25 OHD LEVELS TESTED IN 23 PATIENTS March 2008

26. 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)

27. 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

28. 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

29. Vitamin D supplementation
For every 40 IU of D3 given, serum OH D increased by ng/ml
Rx for deficiency
PO: 50,000 units of D3 q week x 6-8 weeks, then IU daily
IM : D3 (300,000 IU) in 1 or 2 doses per year
Rx for Insufficiency
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

30. 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

31. 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

32. 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

33. B12 level Normal-> 300 pg/ml cobalamin deficiency unlikely
Borderline deficiency possible
Low < 200 -deficiency

34. 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

35. 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

36. 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%)

37. 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

38. B 12 LEVELS OVER TIME NHCU

39. 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

40. Dosing of B12 Few studies to guide dosing
If pernicious Anemia dose of IM B12 is mcg/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

41. 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

42. 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%

43. 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

44. 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

45. Recommendations for folate supplementation
Do NOT take folic acid for reducing cancer risk
Evidence unclear and limited regarding association between hypertension and hearing loss

46. Toxicity Water soluble vitamins Fat 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

47. 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

48. 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)
3. Villareal, Dt,et al, J Clin Endocrinol Metab, 991, Mar ;72 (3) :
4.Bischoff-Ferrari, Ha, et al, JAMA, 2004, April 28;291(16):
5. Broe, KE, et al, J Am Geriatr Soc 2007 Feb;55(2)234-9