1. Iron and Health The SACN Report Professor Peter J Aggett On behalf of SACN profpjaggett@aol.com

2. In the beginning:- 1998 “There is moderate evidence of a relationship between red and processed meat consumption and colorectal cancer.” “Lower consumption of red and processed meat would probably reduce the risk of colorectal cancer”

3. Risk Management:- 1998 “..individual’s consumption of red and processed meat should not rise;..” “Adults with intakes of red and processed meat greater than the current average, especially those in the upper reaches of the distribution…. should consider a reduction in intake” it is not recommended that adults with intakes below the current average, should reduce their intakes.” (at that time: average consumption of red and processed meats was around 90 g/day cooked weight, consumers higher consumers ate this140g/day)

4. Caveat:- COMA 1998 Possible adverse implications of a reduction in meat consumption on other aspects of health, particularly iron status…should be the subject of review. Iron and Health Review

5. Terms of Reference To review the dietary intakes of iron in its various forms and the impact of different dietary patterns on the nutritional and health status of the population and to make proposals.

6. The terms of reference of the Iron Working Group It was agreed that it was necessary to consider both beneficial and adverse effects of increasing iron intakes, including the: – effect of dietary components on iron absorption and utilisation in the body; – interaction of infections and inflammation with iron metabolism and the possibility that this may affect the apparent incidence of iron deficiency; – effect of iron deficiency on health and well-being, for example mental and physical development; – potential adverse effects of excess iron, including free radical damage and the risk of cardiovascular disease (CVD) and cancer. The associations between consumption of red and processed meat and cancer risk were also considered since these foods contain high levels of iron.

7. 1:Effect of dietary components on iron absorption and utilisation in the body Iron is essential, ubiquitous and potentially toxic The body only absorbs as much as it needs and can not excrete excess iron; tightly regulated Vitamin C enhance iron uptake by gut Phosphate compounds (phytates: caseins), calcium salts, and polyphenols reduce uptake by gut Vegetarians and low meat consumers are not necessarily at an increased risk of iron deficiency.

8. 2: Interaction of infections and inflammation with iron metabolism and the possibility that this may affect the apparent incidence of iron deficiency Infections, and inflammation give a false impression of iron deficiency: mediators of inflammation – reduce gut uptake and transfer of iron – Increase deposition of iron in tissues [Chronic inflammatory conditions and obesity] Infections may increase loss of blood via gut and kidneys, causing anaemia and loss of iron and other nutrients (intestinal worms) Malnutrition-Infection cycle underpinning anaemia and iron deficiency: confuses interpretation of effects of “iron deficiency anaemia” reported from such LDCs

9. 3: Effect of iron deficiency on health and well-being, for example mental and physical development Severe “iron deficiency anaemia” (at levels not usually seen in the UK i.e. <80g Hb/L, but no threshold identified) is associated with impaired – Psychomotor and cognitive development and function – Physical performance and work capacity – Some aspects of immune function Effects not seen above 110 gHb/L Pregnancy outcome Problem is identifying iron deficiency per se, separating from effects of anaemia in general and other external influences.

10. 4: Potential adverse effects of excess iron, including free radical damage and the risk of cardiovascular disease (CVD) and cancer. Acute exposure to large doses: acute GI effects & shock Inherited defects of iron absorption lead to accumulations of iron that are potentially toxic have such “free radical” damage BUT in general populations there is no evidence of high iron body burden causing free radical damage, CVD, neurological damage, or cancer Higher intakes may interfere with use of zinc and copper (linear growth retardation in young children)

11. Uncertainties make it difficult to determine or characterise dose- response relationships the risks associated with iron deficiency or iron excess dietary iron intakes; poor correlation between intakes and systemic iron load; measuring adaptive and functional responses to variations in iron intake; uncertain and possibly conservatively high estimates of DRVs; lack of good markers of iron deficiency or excess; inconsistent quality control and reference values for customary markers of iron status; inadequate characterisation of the role of iron deficiency anaemia and the relative role of iron deficiency and other causes of anaemia in studies investigating the health consequences of iron deficiency; confounding by other dietary and lifestyle factors and by alterations in iron metabolism in response to infection.

12. Conclusions It is recommended that a public health approach to achieving adequate iron status should emphasise the importance of a healthy balanced diet that includes a variety of foods containing iron substantial proportions of the UK population appear to have iron intakes below dietary recommendations for iron, this is not clearly consistent with the low prevalence of poor iron status DRVs for iron should be reviewed when more data become available Some groups may be at risk of iron deficiency anaemia; toddlers, girls and women of reproductive age (particularly those from low income groups) and some adult groups aged over 65 years. Health professionals should be alert to the increased risk of iron deficiency anaemia in these groups

13. Recommendations: 1 A more coordinated approach to research on iron in the UK and elsewhere is required to characterise iron status, involving harmonisation of reference ranges and analytical quality control for markers of iron metabolism. This would improve the cost effectiveness of the research and enable research findings to be more relevant to public health needs. Good quality dose-response data are required to enable a reassessment of the DRVs for iron.

14. Recommendations: 2 Expand knowledge of the systemic regulation and mediation of iron homeostasis to underpin public health and clinical nutritional science needs for iron. Future studies assessing the relationship between iron excess and chronic disease should employ a standardised approach to measure iron exposure and categorisation of red and processed meat and other sources of organic and inorganic iron. Improve food iron content databases, Improve the quality of dietary assessments of iron intake for studies relating to iron and chronic disease.

15. Recommendations: 3 Iron intakes and iron status of vulnerable groups, particularly minority ethnic groups and infants aged up to 18 months, need to be better characterised. An improved understanding is required of the factors underlying the risk of iron deficiency anaemia in vulnerable groups e.g. women of reproductive age from low income populations, etc. The extent to which foods fortified with iron contribute to the supply of absorbed iron and to achieving adequate iron status, particularly in vulnerable groups, should be assessed.

16. The associations between consumption of red and processed meat and cancer risk were also considered since these foods contain high levels of iron. New information since that reviewed in 1998 used for further Chemical Risk Assessments by FSA, including the Committee on Mutagenicity, and the Committee on Toxicity.

17. Iron and Colorectal Cancer: conclusion Overall, there are insufficient data on the association between colorectal cancer risk and dietary intakes of total iron, haem iron, iron status, or heterozygosity for hereditary haemochromatosis to reach clear conclusions.

18. Meat and Risk of Colorectal cancer The …. prospective epidemiological data that have accumulated since (1998)… consistently indicates an increased colorectal cancer risk associated with high intakes of red and processed meat. Overall, the available epidemiological evidence suggests that red and processed meat intake is probably associated with increased colorectal cancer risk.

19. Meat and Risk of Colorectal Cancer The evidence for an increased colorectal cancer risk is not unequivocal.…..effects of confounding by other dietary or lifestyle factors…..cannot be excluded. A number of plausible biological mechanisms have been proposed to explain the association between red meat and colorectal cancer risk, none is supported by convincing evidence. It is not possible to identify if there is a dose-response or a threshold level of red and processed meat which may be associated with increased colorectal cancer risk because of a number of limitations in the data.

20. Risk Assessment Recommendation on CRC to Risk Managers Links between red and processed meat consumption and colorectal cancer risk in 1998 and the evidence that has accumulated since then generally supports this association. It is not possible to determine quantities that may be associated with increased colorectal cancer risk because of limitations and inconsistencies in the data. It may be advisable for adults with relatively high intakes of red and processed meat (e.g., it is estimated that those above the 75th percentile consume over 90 g/day) to consider reducing their intakes.