Nurulain Othman

P83086

20th October 2015

Folate & Function

• The ord folate is deri ed fro the Lati root foliu = Leaf • Folate is important in DNA and methylation cycles, and red blood

cell formation

Deficiencies

• Folate losses via excretion from the urine, skin and bile.

• Resulting in anemia, leucopenia, and thrombocytopenia.

• Reduction in cell division in the lining in the gut – prone to infection, secondary malabsorption.

• Elevation in plasma homocysteine – associated with cardiovascular disease.

Symptoms & Deficiencies

• Symptoms: Weakness, fatigue, difficulty in concentrating, irritability, headache, palpitations, and shortness of breath.

• Folate deficiency during pregnancy can results in neural tube defects e.g. spina bifida, anencephaly, encephalocele

Food sources

• Abundant in green leafy vegetables, legumes.

• >3 servings per day of green leafy vege

• Fortified food with folate such as bread, oat etc.

Bioavailability

• In natural food – reduced as much as 25-30%.

• Affected by the removal of the polyglutamate chain by the intestinal conjugase.

• Synthetic folic acid – approximately 100%

Dietary Folate Equivalents

• Folic acid recommendation is expressed as dietary folate equivalents (DFE)

• Differences in the absorption of food folate, synthetic folic acid from supplements and food fortified with folic acid.

• Supplements – 100% bioavailable.

• Food fortified (folic acid consumed with natural food)– 85% bioavailable.

• Natural food folate, estimation from study by Sauberlich et al. (1987), - 50% bioavailable.

• 1 µg of DFE = 1.0µg food folate

= 0.6 µg folic acid added to foods

= 0.5 µg folic acid taken without food

• 1 µg folic acid as a fortificant = 1.7µg DFE

• 1 µg folic acid as a supplement, fasting = 2.0µg DFE

Dietary Folate Equivalents

Interaction with nutrients and drugs

• Certain fiber e.g. wheat bran may decrease the bioavailability of certain forms of folate

• Alcohol intake impaired intestinal folate absorption and hepatobiliary metabolism and increasing renal folate excretion.

• Medications such as nonstreroidal anti-inflammatory, anticonvulsants, methotrexate and oral contraceptive agents may exert antifolate activity.

Function Age Recommendation Age Tolerable Upper Level

0-5 months 80 µg/day DFE Not possible to establish

6-11 months 80 µg/day DFE

1-3 years 160 µg/day DFE 1-3 years 300 µg/day DFE

4-6 years 200 µg/day DFE 4-8 years 400 µg/day DFE

7-9 years 300 µg/day DFE 9-13 years 600 µg/day DFE

Boys 10-18 years 400 µg/day DFE Adolescents

14-18 years

800 µg/day DFE

Girls 10-18 years 400 µg/day DFE

Men 19-65 years 400 µg/day DFE Adult Men 1000 µg/day DFE

Women 19-65

years

400 µg/day DFE Adult Women 1000 µg/day DFE

Men >65 years 400 µg/day DFE

Women >65 years 400 µg/day DFE

Pregnancy 600 µg/day DFE 14-18 years

≥ 9 years

800 µg/day DFE

1000 µg/day DFE

Lactation 500 µg/day DFE 14-18 years

≥ 9 years

800 µg/day DFE

1000 µg/day DFE

The tolerable upper intake level (UL) as suggested by IOM (1998)

Function

Iron in the body exist in four classes:

• Iron containing heme proteins in hemoglobin, myoglobin and cytochromes – important for oxygen transport and electron transport

• Iron Sulphur enzyme (flavoproteins, heme-flavoproteins) – energy metabolism

• Iron storage and transport protein (transferrin, lactoferrin, ferritin and hemosiderin) – iron absorption, transport and storage

• Other iron-containing or activated enzymes (Sulphur, nonheme enzymes)

Food sources

• Two types of iron in foods – haem iron and non-haem iron

• Haem iron – meats, fish, seafood, and poultry (40%)

• Non-haem iron – plant foods: breads, cereals, dark leafy vegetables (spinach, fern shoots, kangkung), legumes and eggs

Deficiencies

• Impair work performance: reduction in tissue oxidative capacity, which affect endurance and efficiency.

• Decrease in hemoglobin concentration affects work output. (Haas and Brownlie, 2001)

• Impair performance in tests of mental and motor function in childhood. It is reversible when iron was given and anemia corrected. (Grantham-Mcgregor & Ani, 2001)

• Significant problem in pregnancy (IOM, 2001) • Increase perinatal maternal mortality with severe anemia (hemoglobin <40g/l)

• Two fold risk of maternal death with moderate anemia (hemoglobin <80g/l)

• Heart failure, hemorrhage and infection have been identified as possible causes.

• Maternal anemia associated with premature delivery, low birth weight and increased infant mortality.

• Also li it the i fa t’s iro status

• High haemoglobin concentration at the time of delivery are also associated with adverse pregnancy outcomes: small for gestational age.

• Iron deficiency limits the expansion of the maternal erythrocyte cell mass while elevated hemoglobin level decrease plasma volume – hypertension and eclampsia.

Factors affecting iron requirement

• From Loh & Khor (2010) The prevalence of anaemia being highest among the Indians (26.4%) and lowest among the Malays (16.4%). The prevalence of IDA was highest in Indians (18.0%) followed by Chinese (9.9%) and Malays (4.3%). Intake of iron was the highest for the Indians (16.0 mg/d) and the lowest for the Chinese (11.3 mg/d).

• Iron status of subject • Increase absorption when stores are low and decreasing when iron are high. • Iron stores are first depleted (serum ferritin is lowered), concomitant reduction in

the concentration of Hb

• Types of iron • Dietary haem iron is better absorbed because haem is soluble at the pH of the small

intestine. • Non heam iron used for fortification of food is partially absorbed. • Haem iron can be converted to non-haem iron if foods are cooked at a high

temperature for too long.

• Enhancing and inhibiting factors

• Enhancing absorption – ascorbic acid and organic acid; meat chicken, fish and seafood; fermented vegetables and fermented soy sources

• Inhibiting factors – phytates and inositol phosphates; iron-binding polyphenols; calcium; soy proteins and vegetables protein

Bioavailability

• Determined by: the amount of body stores of iron

• The absorption varies from about 40% during iron deficiency to about 10% during iron repletion.

• The properties of diet

• The absorption of non-haem iron is depending on the presence of enhancing or inhibiting factors.

Toxicity

• Excess of iron generate reactive oxygen species.

• DNA damage, impaired synthesis of macronutrients, altered cell proliferation.

• Free iron react with unsaturated fatty acid to form alkoxyl and/or peroxyl radical, which leading to cell death.

• Play role in carcinogenesis, atherosclerosis, neurodegerative disorders e.g. Parki so ’s or Alzhei er’s diseases

Age % Bioavailability (mg)

10 15

0-5 months Can be met by iron provided through breast milk

6-11 months 9 6

1-3 years 6 4

4-6 years 6 4

7-9 years 9 6

Boys 10-14 years

Boys 15-18 years

15

19

10

12

Girls 10-14 years1

Girls 10-14 years

Girls 15-18 years

14

33

31

9

22

21

Men 19 and above 14 9

Women 19 and above

Premenopause

Postmenopause

14

29

11

9

20

8

Pregnancy 20 20

Lactation 0-12 month

7-12 months2

15

32

10

21

1 Non menstruating 2 lactating women with menstruation

Tolerable upper intake levels

• Tolerable upper intake levels (UL)

• Infants and children (0-9 years) 40mg/day

• Adolesce ts a d adults ≥9 years 45mg/day

Conclusion

• There are many more studies need to be done to obtained data on the bioavailability of the nutrients, total intake of the nutrients among Malaysian, and how diet pattern of Malaysian affect the nutrient intake.

Reference • Chew, S.C., Loh, S.P. and Khor, G.L, Determination of folate content in commonly consumed Malaysian foods, International Food

Research Journal 19(1): 189-197 (2012)

• Crider, K. S., Yang, T. P., Berry, R. J., & Bailey, L. B. (2012). Folate and DNA Methylation : A Review of Molecular Mechanisms and the E ide ce for Folate ’ s Role. A erica “ociety for Nutritio , , –38.

• FAO/WHO (2002). Folate and folic acid. In: Human Vitamin and Mineral Requirements. Reorts of a Joint FAO/WHO Expert Consultation. FAO, Rome; p 53-63

• FAO/WHO (2002). Iron. In: Human vitamin and mineral requirements. Report of a Joint FAO/WHO Expert Consultation. FAO, Rome; pp 195-221.

• Grantham-McGregor S & Ani C (2001). A review of studies on the effect of iron deficiency on cognitive development in children. J Nutr 131(2S-2):649S-666S Haas JD & Brownlie T (2001). Iron deficiency and reduced work capacity: a critical review of the research to determine a causal relationship. J Nutr 131(2S-2): 676S- 688S

• IOM (1998). Folate. In: Dietary References Intakes for Thiamine, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin and Choline. Food and Nutrition Board, Institute of Medicine. National Academy Press, Washington DC; chapter 8, pp 196-305.

• Khor, G. L., Duraisamy, G., Loh, S. P., & Green, T. (2006). Dietary and blood folate status of Malaysian women of childbearing age. Asia Pacific Journal of Clinical Nutrition, 15(3), 341–9.

• Loh, S. P., & Khor, G. L. (2010). Iron intake and iron deficiency anaemia among young women in Kuala Lumpur. Malaysian Journal of Medicine and Health Sciences, 6(January), 63–70.

• National Coordinating Committee on Food and Nutrition (NCCFN), Ministry of Health Malaysia. Recommended Nutrient Intakes for Malaysia. Putrajaya, Ministry of Health Malaysia, 2005

• Sauberlich HE, Kretsch MJ, Skala JH, Johnson HL & Taylor PC (1987). Folate requirement and metabolism in nonpregnant women. Amer J Clin Nutr 46: 1016-1028