دکتر زهرا عبداللهي اداره بهبود تغذيه جامعه اداره بهبود تغذيه جامعه معاونت بهداشت. وزارت بهداشت، درما ن و آ موزش پزشكي معاونت بهداشت. وزارت بهداشت، درما ن و آ موزش پزشكي نقش اسيد فوليک در سلامت نقش اسيد فوليک در سلامت

اسيد فوليك اسيد فوليك ( فولات ) يكي از ويتامين هاي گروه B و محلول در آب بشمار مي رود. نام فولات از اسم لاتين فوليوم Folium به معناي برگ گرفته شده است. درسال 1931 دكتر Lucy wills دريافت كه فولات يك ماده مغذي ضروري براي پيشگيري از كم خوني در دوران بارداري است.

اسید فولیک / فولات فرم طبیعی اسیدفولیک در منابع غذایی فولات نامیده می شود. اسید فولیک در مکمل های ویتامینی و غذا های غنی شده وجوددارد. زیست دسترسی اسید فولیک دو برابر فولات است ( قابلیت جذب فولات غذایی درحدود 50% اسید فولیک است ) اسید فولیک پس از جذب به فولات تبدیل می شود.

Metabolism The role of folate coenzymes: Transfer of one carbon unites Vital role in DNA synthesis from its precursors (thymidine and purines( Synthesis of methionine Metabolism of several important amino acids such as methionine, histidine, serine, and glycine

Functions 1- Human Reproduction : During the periconceptional period, helps protect against a number of congenital malformations including Neural Tube Defects (NTDs) Low sperm count and decreased sperm density

Functions 2- DNA and cell division : Folate is needed to synthesize DNA and also needed for DNA replication. Thus, folate deficiency hinders DNA synthesis and cell division. Since folate deficiency limits cell division, erythropoiesis, production of red blood cells is hindered leads to megaloblatic anemia which is characterized by large immature red blood cells

شیوع کمبود اسید فولیک تخمين زده شده است كه در جهان، سالانه 300 هزار كودك به دليل كمبود اسيد فوليك با نقايص مادرزادي لوله عصبي متولد مي شوند 75% اين موارد با مصرف مكمل اسيد فوليك در زنان سنين بارداري قابل پيشگيري است

شيوع كمبود فولات منطقه كمبود فولات سرم كمبوددريافت گروه مورد بررسيسال بررسي اسلام شهر 12/495% زنان باردار دانشگاه شهيد بهشتي 28- زنان سنين باروري 1384 استان تهران 98% ( <11nmol/l) - زنان سنين باروري استان گلستان 14/398% زنان سنين باروري 1385 ايالات متحده امريكا 16%- NHANS لبنان 25% - زنان سنين باروري 2003 سريلانكا 57% - زنان باردار هندوستان 42% - زنان باردار تايلند 15% - زنان باردار

Recommended Daily Value of Folic Acid Non-pregnant women and men aged 14 yrs and older 400 mcg synthetic + food Pregnant women* and women planning a pregnancy 600 mcg synthetic + food Breastfeeding women 500 mcg any source 9-13 years (boys and girls) 300 mcg 4-8 years (boys and girls) 200 mcg 1-3 years (boys and girls) 150 mcg * Women with previous NTD-affected pregnancy should talk to their doctor

Foods Naturally High in Folic Acid Liver Nuts and peanut butter Dried peas or beans Juices: orange, pineapple, tomato Fruits: orange, avocado, cantaloupe Leafy green vegetables

Dietary Folates/FA orange juice spinach turnip greens85 ? Asparagus101 ? pinto beans147 ? beef liver fortified bread (slice) fortified noodles fortified brkf. Cereal100 or Food Avg. µg in serving Bioavailability (%)

Bioavailability of Food Folates Folates are lost from foods by: - preparation (heat, oxidation, leaching into water) - inhibition of essential gut enzymes by inhibitors in food, extremes in pH and rapid transit time Under controlled conditions, 30-80% of folate is absorbed

Causes of deficiency Inadequate ingestion of folate-containing foods Impaired absorption : - (Celiac disease and tropical Sprue - Achlorhydria - Anticonvulsant drugs, such as Dilantin, - nutrient deficiencies such as zinc, riboflavin, niacin and vitamin B12

Causes of deficiency Impaired metabolism : - Methotrexate and trimethoprim -Hypothyroidism --alcoholism  Increased excretion /loss (vitamin B-12 deficiency )  Increased destruction (smoking )

Nephrosclerosis Atherosclerosis Elevated Homocysteine Primary arterial thrombosis Myocardial infarction Stroke Atherosclerosis ? Low folate Low vitamin B 2 Low vitamin B 12 Low vitamin B 6 MTHFR mutant Other Venous thrombosis Venous thromboembolism Hyperhomocysteine 與 Atherosclerosis

Folic acid deficiency Anemia Stage 1: serum folate level is less than 3ng/ml : serum folate depletion. Stage 2 reduction in red blood cell folate levels to less than 140ng/ml Stage 3 damage of folate metabolism and slowed DNA synthesis Stage 4 Elevated MCV and anemia that is named folate deficiency anemia.

Neural Tube Defects NTDs are malformations of the developing brain and spinal cord NTD closure occurs during the fourth week of embryosis Numerous studies have shown a 50% to 100% reduction in NTDs by taking.4 mg of folic acid daily

Spina Bifida Neural tube fails to close properly: Occurs by 28 gestational days Associated problems: Hydrocephalus Clubfoot Vertebral anomalies Renal anomalies Requires surgery hours after birth

Financial Costs: Financial Costs: Average estimated lifetime cost of $532,000 for each infant born with spina bifida (CDC 1999) Physical Costs: Physical Costs: Possible paralysis), bowel and bladder control problems, learning disabilities, hydrocephalus, surgical procedures, increased health problems with age Emotional Costs: Emotional Costs: Miscarriage, stillbirth, infant mortality (death before 1st birthday), disability, feeling “different” The High Cost of NTDs

Folic Acid supplementation and NTDs Pre pregnancy folic acid supplements prevented neural tube defects in 1980s Supplements to women in age of fertility achieves >1/3 coverage, 1990s (US) FDA mandates flour fortification with folic acid from 1998

Intervention = 400 mcg folic acid supplement daily NorthSouth 41% NTD Rate/ % No Pills Pills Berry RJ, et al., NEJM 1999; 341: China Folic Acid supplementation

Folic acid may prevent hypertension women who consumed at least 1,000 μg/d of folate from dietary and supplemental sources: 46% reduction in risk of hypertension JAMA. 2005;293:

Folic acid and AD Overall healthy diets have impact on limiting Alzheimers and Dementia risks. Folate appears more beneficial than other nutrients. Those who took Folic Acid (above 400 mcg.) had 55% risk. Ref: Alzheimers and Dementia: Journal of the Alzheimer’s Association, 2005

Colon Cancer Nurses’ Health Study cohort After 14 years of follow-up, women consuming at least 400 mcg/d of total folate had a 31% decreased risk of colon cancer. After 15 years of taking a vitamin supplement with folic acid, relative risk of colon cancer was decreased by 75%.

Folate/Zinc interaction Animal modle studies have shown that hepatic methionine synthesis activities were increased in zinc deficient rats. This increased resulted in a decreased 5- methyltetrahydrofolate in the liver of zinc deficient rats. Furthermore, plasma folate and homocysteine were lower in zinc deficient rats

Barriers to Folic Acid Absorption or Use Alcohol Tobacco Aspirin, ibuprofen, naprosyn and acetaminophen Antacids & anti-ulcer medications Some antiseizure medications Some anticancer drugs Some antibiotics/ antibacterials Oral hypoglycemic agents Source: Folicacid.net.

غني سازي آرد با آهن و اسيد فو ليك درایران : دربرنامه ملي غني سازي آرد با آهن واسيد فوليك ، 1/5 ppm اسيدفوليك به آرد اضافه مي شود. با مصرف نان غني شده 30% نياز روزانه به آهن و 56% نياز روزانه به اسيد فوليك تامين مي شود

میانگین هموسیستین پلاسما در زنان سنین باروری ،قبل وبعد از غنی سازی آرد دراستان گلستان P=0.000

میانگین فولات سرم در زنان سنین باروری ، قبل وبعد از غنی سازی آرد دراستان گلستان P = 0.000

شیوع نقایص مادرزادی لوله عصبی ، قبل وبعد از غنی سازی آرد دراستان گلستان P<0.01

شیوع کمبود فولات سرم و هموسیستئین بالا درزنان سنین باروری، قبل وبعد از غنی سازی آرد با اسید فولیک P = 0.000

Molecular mechanisms affected by folic acid

Folate deficiency also causes neurological defects and anemia Adequate levels of folate are particularly critical during the development of the nervous system. A shortage of folate in this period can cause neural-tube defects, including spina bifida. Anemia caused by folate deficiency is very similar to that caused by B 12 deficiency (pernicious anemia). But if the problem is pernicious anemia, folate could remedy the anemia but not prevent damage to the nervous system. Folate deficiency is probably the most common vitamin deficiency. Since addition of folate to flour in the U.S. began in 1996, neural-tube birth defects have decreased by ~20%. A recent study concluded that adding folate to food also has decreased deaths from heart attacks & stroke by 48,000/year.