Folic acid status in Europe

Folate and related B vitamins An Evaluation of Adequacy from a European Perspective Helene McNulty Northern Ireland Centre for Food and Health (NICHE) University of Ulster

Folate and metabolically related Bvitamins Folate Vitamin B-12 Vitamin B-6 Riboflavin

Terminology to describe “folate” intake • folic acid: – synthetic form (supplements, fortified foods)

• folates: – natural forms (plant and animal tissues)

Folate and related B-vitamins This talk will cover

• the problem • potential solutions

Optimal folate and related B-vitamin status Opportunity for disease prevention

• • • • •

Neural tube defects Heart disease and stroke Cancer Neuro-psychiatric disease Osteoporosis

Evidence conclusive convincing promising possible role possible role

The problem Current folate intakes are suboptimal in European populations

Prevalence rates of NTD in Europe 18

Rate per 10,000 births

16 14 12 10 8 6 4 2 0 Glasgow Galway

Dublin

France

Spain

Source: EUROCAT Central Registry, Brussels

Belgium Denmark

Italy

Switz.

Folate recommendations for the prevention of NTD UK USA Australia Canada

Department of Health (1992) Centres of Disease Control and Prevention (1992) National Health and Medical Research Council (1993) Health Protection Branch of Health and Welfare (1993)

Current recommendations for the prevention of NTD To be commenced prior to conception and during the first 12 weeks of pregnancy: – 400 microgram folate/folic acid per day

Rates of NTDs per 10 000 births, 1988-98 Botto et al BMJ 2005;330:571-576

Adequate versus Optimal folate intake • The “average” diet • provides adequate folate intake to prevent megaloblastic anaemia in healthy people • is insufficient in providing optimal folate intake to lower the risk of NTD and possibly other disease

Potential solutions to achieve optimal folate status Natural food sources

Fortified Foods

Option 1 Natural food folates

Natural food folates v Folic acid • Food folates are reduced molecules • Food folates are predominantly polyglutamates but converted to monoglutamates for absorption

Folate loss from spinach during cooking % Retention of folate

120 100 80 60 40

boiled

20

steamed

0 0

2

4

6

8

Time (minutes)

10

12

14

16

Option 1: Natural food folates • The potential to optimise folate status by natural food folate sources is very limited • Food folates • may be unstable during cooking • show incomplete bioavailability once ingested

Option 2 Folic acid supplementation

Timeframe for Preventing NTDs Neural tube closes 21-28 days after conception‌. .......just when most women are beginning to suspect they might be pregnant!

Awareness of folic acid supplement use

by Irish women1,2 Only 20-25% use folic acid supplements at the correct time for preventing NTDs (even when the pregnancy is a planned one)

1The

Coombe Women’s Hospital, Dublin (2001/2002; personal communication) 2Causeway

Hospital, Coleraine Northern Ireland (2006/2007) (McNulty et al in preparation)

Option 3 Folic acid fortification

Current folic acid fortification policy in North America

Impact of folic acid-fortified food on folate intake and status Hoey et al AJCN 2007; 86: 1405-1413 NonConsumers (n=97)

Low Consumers (n=111)

Medium Consumers (n=118)

High Consumers (n=115)

(FA= 0µg/d)

(FA=1-39µg/d)

(FA 40-98µg/d)

(FA ≥ 99µg/d)

Total folate (µg/d)

186 (142, 223) a

206 (173, 246) a

259 (212, 310) b

422 (333, 549) c

Added folic acid (µg/d) Natural folate (µg/d)

0 (0, 0) a 186 (142, 223) a

25 (17, 33) b 179 (151, 215) a

60 (50, 75) c 196 (150, 248) a

208 (125, 291) d 197 (157, 238) a

Plasma tHcy (µmol/l)

11.5 (9.4, 13.9) a

10.7 (8.9, 13.4) a

9.6 (7.8, 11.2) b

9.4 (7.7, 12.0) b

RCF (nmol/l)

653 (532, 830) a

697 (564, 857) a

862 (680, 1082) b

1040 (798, 1413) c

15.1 (10.0, 21.1) a

16.2 (11.6, 22.1) a

22.6 (16.7, 30.5) b

30.1 (21.5, 45.5) c

Dietary Folate Intake

Folate Status

SF (nmol/l)

Options to achieve optimal folate status-

Intervention

Strategy likely to be effective? individual population

natural food folates supplementation fortification

no yes yes

no no yes

Prevalence and Consequences of vitamin B12 deficiency • Low/deficient status is highly prevalent among healthy elderly in Europe – Affects up to 40% depending on the diagnostic criteria – Only 1-2% of cases explained by classical B12 deficiency (pernicious anaemia)

• Food-bound B12 malabsorption considered to be the main cause – Owing to atrophic gastritis with hypochlorhydria

• Consequences of B12 deficiency - classical – Haematological abnormalities – Neurological complications (irreversible nerve damage)

• Other health consequences – CVD; Cognitive impairment; Ostoporosis

Prevalence of riboflavin deficiency • Clinical deficiency is rare in Western societies as dietary intakes are generally adequate BUT UK NDNS data (2004): • High prevalence of suboptimal status (EGRac >1.3) – 66% of UK adults aged 19-64y – 41% of UK adults aged >65y • High prevalence of suboptimal status among adolescents, especially girls (95% of girls aged 15-18y) • Probably due to an age-related decline in milk consumption

Take-home messages • Folic acid has – a proven beneficial effect in NTD – probable benefits in preventing CVD, especially stroke, presumably via homocysteine-lowering effect

• Folate-related B vitamins have – additional roles in preventing homocysteine accumulation (vitamins B-12 and B-6) – particular relevance in the face of genetic predisposition to high homocysteine levels (riboflavin)

• However, the typical diet in Europe is sub-optimal in folate, and possibly in related B-vitamins in certain population groups

Folate research at UU The Current Players NICHE

Our Collaborators in TCD

Helene McNulty Sean Strain Mary Ward Kristina Pentieva Leane Hoey

John Scott Anne Molloy

Clinical Collaborators

International Collaborators

Owen Finnegan, Causeway Hospital Barry Marshall, Causeway Hospital James Dornan, RVH Belfast John Purvis, Altnagelvin Hospital

Steve Whitehead, Pennsylvania Per Ueland, Norway