1. Micronutrient supplements in older people- who needs them?
Alan Shenkin
Dept of Clinical Biochemistry & Metabolic Medicine
University of Liverpool/ Royal Liverpool Univ.Hospital

2. The Hypothesis
Optimising micronutrient status in the elderly will improve health and well being, and will reduce illness and mortality.

4. A lot of theory of benefit
BUT
Only a little evidence of benefit

5. The Theory

6. Essential Micronutrients
Identified from clinical signs reversed by
dietary supply of a single micronutrient
Vitamins- water and fat soluble
Trace elements

7. Roles of vitamins and trace elements
Active site of enzymes or cofactors
Coenzymes in intermediary metabolism
Antioxidants, directly or indirectly
Gene transcription factors

8. Classical and new functions of micronutrients
Vitamin C Antiscorbutic Antioxidant
Vitamin K Coagulation factors Bone mineralisation
Zinc Growth factor Immune function
Selenium Prevent myopathy Antioxidant

9. Development of micronutrient deficiency
Optimal tissue levels
Initial depletion -compensation to inadequate supply
Impairment of biochemical functions
Metabolic
Oxidative damage
Membranes/DNA
Functional defects non-specific
Clinical disease
Immunological Cognitive Work capacity
Death

10. The Evidence
1. There is evidence of poor micronutrient status in institutionalised elderly

11. Food sources of micronutrients in people >65 yrs
% RNI
National Diet and Nutrition
Survey,1998

12. Proportion of people >65 yrs with a low status of nutrient
National Diet and
Nutrition Survey,1998

13. The Evidence
2. There is epidemiological evidence that links poor intake of micronutrients with coronary artery disease and with various cancers.

14. The Evidence
3. There is laboratory evidence that links increased amounts of various micronutrients with reduced oxidative damage and improved markers of immune function.

15. What benefits should be seen from preventing or treating a subclinical deficiency?
Metabolic
Reduced infections
Improved cognitive function
Reduced degenerative diseases- e.g.cancer/CAD

16. Evidence of benefit of treatment of subclinical deficiency
Metabolic
Chromium and glucose tolerance
Folate and homocysteine metabolism – relation to coronary artery disease

17. Evidence of benefit of treatment of subclinical deficiency
Folate and homocysteine metabolism – relation to coronary artery disease

18. DIETARY INTAKE

19. Folate and coronary restenosis
Schnyder et al . JAMA (2002) 288:973-9
553 patients who had had successful coronary angioplasty
6 months folic acid(1mg/d), B12(400ug/d), B6(10mg/d) v placebo
Plasma homocysteine:
7.2μmol/l
Need for revascularisation : 16% v 9.9% (p= 0.03)
Composite endpoint at 1 yr: 22.8 v 15.4 (p=0.03)

20. Folate and coronary restenosis
Lange H et al (2004) NEJM 350:
636 patients who had undergone coronary stenting
Folic acid 1.2mg/ B6 48mg/ B12 60 ug daily
6 month follow up
Folate v Placebo: Restenosis 34.5% v 26.5 % p=0.05
Revascularisation 15.8% v 10.6 % p=0.05

21. Evidence of benefit of treatment of subclinical deficiency in the elderly
Micronutrients and infection

22. El-Kadiki & Sutton- BMJ (2005) 330:871-874
‘The evidence for routine use of multivitamin and mineral supplements to reduce infections in elderly persons is weak and conflicting’

23. Three of the positive studies have been seriously questioned
BMJ (2003) 328:67

24. El-Kadiki &Sutton ,2005

25. A. Avenell, M. K. Campbell and J. A. Cook et al
A. Avenell, M.K. Campbell and J.A. Cook et al. (2005) Effect of multivitamin and multimineral supplements on morbidity from infections in older people (MAVIS trial): pragmatic, randomised, double blind, placebo controlled trial, BMJ 331 pp. 324–329.
Liu BA, McGeer A, McArthur MA, et al (2007)
Effect of Multivitamin and Mineral Supplementation on Episodes of Infection in Nursing Home Residents:
A Randomized, Placebo-Controlled Study J Amer Ger Soc 55 (1) , 3 5–42

26. Liu et al 2007
748 subjects, mean age 85, from 21 long term care nursing homes in Toronto area
One multimineral and vitamin supplement per day or placebo over 19months
Overall risk of infection not reduced
In subgroup without dementia, significant reduction (19%) in infections

27. Evidence of benefit of treatment of subclinical deficiency in the elderly
Folate and homocysteine metabolism
Immune function
Cognitive function

28. Micronutrients and Cognitive Function in the elderly
Chandra RK Nutrition (2001) 17:
Effect of vitamin and trace element supplementation on cognitive function in elderly subjects

29. Micronutrients and Cognitive Function in the elderly
Cochrane Library reviews (2003) of folic acid, vitamin B12 and vitamin B6 have shown found no evidence for any improvement of cognition or dementia

30. Clarke et al (2007) Am J Clin Nut 86: 1384-91
1648 subjects followed for 10 years- low vitamin B12 status associated with more rapid cognitive decline
Kwok et al (2007) Arch Gerontol Geriatr (Epub)
30 mild to moderate dementia subjects with low vit B12 status. Supplementation for 40 weeks did not affect cognitive function, but reduced episodes of delirium

31. Micronutrients and Cognitive Function in the elderly
Wouters-Wesseling et al J Gerontol ( 2005) 60A,
101 residential home adults received enriched drink (energy/protein and micronutrients) or placebo for 6 months
Significant improvement in some aspects of cognitive function- word learning test p=0.014

32. Evidence of benefit of treatment of subclinical deficiency in the elderly
Folate and homocysteine metabolism- CAD
Infections and immune function
Cognitive function
Osteoporosis – Ca and Vit D

33. DRIs for older adults:
Only for vitamin D is there a difference between the DRIs for year olds (10 μg/day) and those 70+ (15μg/day)

34. What benefits should be seen from preventing or treating a subclinical deficiency?
Metabolic
Reduced infections
Improved cognitive function
Reduced degenerative diseases- e.g.cancer/CAD

35. Antioxidants and Heart Disease
Some small studies have suggested beneficial effects of vit E
HOPE study- NEJM(2000)342, patients with high risk of CHD-400IU Vit E + ACE inhibitors- no benefit
GISSI study- Lancet(1999)354, patients post MI-PUFA/VitE(300mg)
or both
-PUFA beneficial but not Vit E

36. Antioxidants and Heart Disease
MRC/BHF study-Lancet(2002)360,23-33
20333 high risk UK adults
VitE (600mg), vitC(250mg),βcarotene(20mg)- 5years
No significant benefit- increase in triglycerides and LDL

38. Vitamin E and mortality
Miller et al. Ann Intern Med. (2005)142:37-46
19 clinical trials- 135,967 participants
9 trials of vitamin E alone
High dose vitamin E 400 IU/d or more may
increase all cause mortality.
Possibly increased risk >150IU/d

39. Miller et al, 2005

40. Prevention/Treatment of subclinical deficiency and cancer
A lot of theoretical and epidemiological
evidence of potential benefits of
antioxidants.

41. Antioxidants and cancer
Albanes et al (1995) Am J Clin Nutr 62(supp)
Finnish male smokers 5-8 years follow up
β-carotene(20mg),α-tocopherol(50mg) or both
18% higher incidence of lung cancer in βcarotene group
α-tocopherol had no effect

42. Antioxidants and cancer
Omenn et al. NEJM(1996)334,1150-5
18314 smokers,former smokers,asbestos workers
30mg β carotene, IU vitamin A year follow up
supplemented group had relative risk of lung cancer of 1.28

43. Antioxidant supplements for prevention of gastrointestinal cancers;a systematic review and meta-analysis.
Bjelkovic et al.Lancet 2004,364:

44. SU.VI.MAX Study
13017 adults from general population in France( aged <60)
Antioxidants ( Vit C 120mg, Vit E 30mg,
β-carotene 6mg, Se 100 µg, Zn 20mg) or placebo
Median follow up time 7.5 yr

45. Results
No major differences in total cancer incidence, ischaemic heart disease or all cause mortality
However sex stratified analysis showed lower cancer incidence and all cause mortality in men but not in women.
Poorer baseline status in men?

46. Effect of Selenium supplements (200ug/day) for 4.5yrs on cancer
Number
of patients
From Clark et al
JAMA,1996,276,1957

47. Antioxidants and eye disease
AREDS studies- Arch Ophthalmol(2001) 119,
VitC(500mg),VitE (400IU),β carotene(15mg), and/or zinc(80mg),copper(2mg) daily
Double blind,placebo controlled study
4629 patients- follow up- 6.3 years

48. AREDS Studies(2001)
No significant difference in development or progression of age- related cataract
Significant reduction in development of age- related macular degeneration

50. Who should receive micronutrient supplements?
General population- poor intake in the typical diet

51. Selenium intake in the UK-μg/day
Modified from Rayman 2001

52. Who should receive micronutrient supplements?
General population- poor intake in the typical diet
Population groups with known poor intake/increased requirements
Individuals where socio-economic situation may affect intake

53. Conclusions
A multiple supplement may be beneficial in at risk groups e.g.institutionalised elderly
Large studies on homogeneous populations are required to define the situations and amounts of micronutrients where benefit is obtained.
Individual micronutrient supplements are beneficial where there is evidence of a deficiency state

54. Conclusion
Supplements should be targeted at
those who need them