Folate and Folic Acid. Ms Brigid McKevith British Nutrition Foundation United Kingdom

Transcription

1 Folate and Folic Acid Ms Brigid McKevith British Nutrition Foundation United Kingdom

2 This work was funded from an Accompanying Measure grant from the European Commission, Quality of Life and Management of Living Resources Programme (QoL), Key Action I (KAI) on Food Nutrition and Health (QLKI-CT ), coordinated by Paul Finglas, Institute of Food Research, Norwich, UK. It is linked with an EU-funded programme of work, Folate: from food to functionality and optimal health (FolateFuncHeath, QLRTI & QLRT ), also coordinated by Paul Finglas, findings from which were presented at a conference in Warsaw in 2004 (EuroFoodFolate).

3 An EU-funded research project FolateFuncHealth has reviewed levels of folate in foods and explored new ways to increase folate intake. Introduction People need a range of different nutrients to maintain health and reduce the risk of dietrelated diseases. One group of nutrients, vitamins, are complex substances that are needed for a range of processes carried out by the body. Although only small amounts are needed - usually only a few milligrams (mg) or micrograms (µg) - vitamins are essential for health. Most vitamins cannot be made by the body, so have to be provided by the diet. This booklet focuses on one of the B vitamins, folate, sometimes called folic acid. Folate and folic acid what are they? Folate is a B vitamin. Rich dietary sources of folate include leafy vegetables, fruits and berries, beans, whole grain products and liver. Nuts, whole-meal bread, and fortified breakfast cereals are also good sources of folate. Table 1 shows some examples of the folate content of selected foods per 100g and per serving. Folic acid is a man-made or a synthetic form of folate, which can be used by the body as a substitute for folate. Folic acid is used in supplements and can be added to foods to increase the total folate content, a process known as fortification. Fortification is currently prohibited in some parts of the EU. In the UK, some breakfast cereals, breads, low fat spreads and other foods are fortified with folic acid. In some countries, such as the USA, Canada and Chile, staple foods (mainly grains and flour) are fortified by law with folic acid to increase the population s intake. For example, in the USA cereal grains are fortified with 140 µg of folic acid per 100g of grain. Although folate (the natural form) and folic acid (the synthetic form) are very similar in structure, folate is not as stable as folic acid - it is more easily damaged by cooking and processing. Also, food folates need to be broken down in the digestive system before the body can absorb them. This means that folic acid is absorbed more efficiently than the natural form of the vitamin.

4 Table 1. Examples of different foods & the amount of folate/folic acid (µg) they provide per 100g and per portion Food Amount (µg) /portion Amount (µg) /100g Cereals & cereal products Yeast extract (thinly spread on bread) Fortified breakfast cereals (30 g portion) Granary bread (medium slice) Wheatgerm bread (36g slice) Rye crispbread (per biscuit) Fruits Raspberries, raw (60 g) Satsumas (medium Satsuma) Oranges (medium orange) Grapefruit (half) Orange juice (glass) Avocado (average portion) Vegetables Asparagus, raw (5 spears) Black-eye bean curry (200g portion) Brussel sprouts, boiled (90g portion) Spinach, boiled (90 g portion) Spinach, frozen, boiled (average portion) Cabbage, raw (90g portion) Spring greens, boiled (95g portion) Broccoli, boiled (85g portion) Green beans, frozen, boiled (90g portion) Cos lettuce, raw (in a salad) Iceburg lettuce, raw (in a salad) Cauliflower, boiled (90g portion) Baby peas, frozen, boiled (70g portion) Parsnip, roast (90g portion) Peas, frozen, boiled (70g portion) Okra, boiled 46 2 (each) Bean salad (200g portion) Leeks, boiled (75 g portion) Cabbage, Savoy, boiled (95g portion) Chick pea curry (210 g portion) Oven chips, thick cut, baked (165 g portion) Meat & meat products Chicken livers, fried (70 g portion) Liver & bacon, fried (100 g portion) Liver pate (on bread) Lamb s kidney, fried (per kidney) Braising steak, slow cooked (140 g portion) Beef mince, cooked (140 g portion) Beef & spinach curry (350 g portion) Lamb or beef hotpot with potatoes (260 g portion) Beef sirloin steak, grilled (8 oz/227 g uncooked weight) Beef, topside, roasted (90 g portion)

5 Table 1. Examples of different foods & the amount of folate/folic acid (µg) they provide per 100g and per portion (continued) Food Amount (µg) Amount (µg) /portion /100g Other foods Peanuts (10 nuts) Tahini paste (heaped teaspoon) Camembert cheese (40 g portion) Hazelnuts 72 7 (10 nuts) Cashew nuts 67 7 (10 nuts) Walnuts (6 halves) Gouda cheese (40 g portion) Cheddar cheese (40 g portion) Milk (1/2 pint or ~250 ml)

6 Why is folate important? Folate has a number of critical functions within the body, including involvement in the production of red and white blood cells, the production of RNA and DNA (which are involved in cell replication) and normal development of the fetus in pregnant women. In the past it was believed that the main outcome of folate deficiency was a type of anaemia (known as megaloblastic anaemia). It is now known that during early pregnancy even a moderately poor folate status (within what is considered the normal range) can increase the risk of neural tube defects (NTDs) in the developing baby, e.g. spina bifida. Low folate status (low blood levels) may be due to: poor diet impaired absorption (e.g. in some digestive disorders such as untreated coeliac disease) treatment with some drugs (e.g. anti-convulsants), and pregnancy, as there is an increased need for folate. Folate and pregnancy Women with a low folate status are more likely to give birth to a low birth weight baby. But folate status is particularly important before conception and during the first 12 weeks of pregnancy. Extra folate at this time can help protect against spina bifida and related conditions. In the early days of pregnancy, an organ called the neural tube forms in the tiny embryo and this is destined to become the baby s brain and spinal cord. The neural tube is fully formed by 26 days after conception, and once this stage is reached the bony structures destined to become the skull and the vertebrae of the spine begin to develop. In conditions such as spina bifida, known as neural tube defects (NTDs), development of the neural tube is incomplete and where the defects in the structure exist, bone fails to form properly, resulting in the characteristic deformities of spina bifida (which affects the spine) and anencephaly (a condition where the skull fails to develop properly). The incidence of NTDs varies from country to country, ranging from 5 cases per 10,000 pregnancies in Switzerland to 29 per 10,000 pregnancies in Glasgow. In the UK, it has been suggested that NTDs may affect between 600 and 12,000 pregnancies each year. It has been estimated that consumption of an extra 400 µg of folic acid per day may prevent 8 out of 10 NTDs. Initial results from the USA and Canada, where folic acid has been added by law to the food supply since the late 1990s, show a reduction in NTDs of between 20% and 50% since fortification began. It is not yet clear whether this is directly related to the fortification policy. However, it is evident that folate status (the concentration of folate present in the blood) has increased dramatically and folate deficiency is now a rarity. As it is difficult to achieve the extra folate needed through diet alone, all women of childbearing age, especially those planning a pregnancy, are advised to take daily supplements

7 (400 µg/day) of folic acid. This is because the vitamin is important at a time when many women do not yet realise that they are pregnant. It is also important to consume foods that are naturally good sources of folate. However, as 30 50% of pregnancies are unplanned, many women who become pregnant will not have considered taking folic acid supplements prior to conception. Taking folic acid after the first 12 weeks will have no impact on NTD risk, but will help prevent low folate status and associated anaemia. Other benefits of folate Pregnancy is not the only time when folate has a role to play in optimal health. Marginal folate deficiency is also associated with an increased risk of other diseases. Heart health Currently there is much interest in the potential impact folate and folic acid may have on heart health. Homocysteine is a sulphur-containing amino acid (amino acids are the building blocks of proteins), produced in the body from another amino acid (called methionine) during the metabolism of protein. The homocysteine level in the blood reflects how much methionine is provided in the diet (there is about three times more methionine in animal protein than in plant protein), and how much is converted to other substances. This conversion can occur by two pathways: one requires vitamin B 12 and folate, and the other vitamin B 6. Low levels of homocysteine are normally found in the blood. However in certain circumstances, often linked to genetic inheritance, levels can rise and an elevated level of homocysteine is one of several factors that play a major role in damaging the lining of blood vessels. It is known that an elevated level of homocysteine in the blood is a risk factor for heart disease and stroke. Folic acid, as well as other B vitamins (including vitamins B 6 and B 12 ), are involved in the processing of homocysteine in the body. They have the potential to reduce homocysteine levels in the blood. Folic acid, in particular, can lower homocysteine levels, although no additional effect is seen with intakes above µg folic acid/day. However, it is still unknown whether a folic acid-stimulated fall in homocysteine leads to an overall decrease in incidence, illness and/or death from heart disease. Studies investigating this are currently under way. Cancer A relationship between folate intake or status and several types of cancer, in particular colon cancer, has been observed in studies comparing risk within or between populations. High folate intake ( µg per day) is associated with lower colon cancer rates. It is not yet clear whether the reduced risk is specifically caused by folate intake (a cause and effect relationship) or whether people who take folic acid supplements are more likely to lead a generally more healthy lifestyle. As with heart disease, there remains a need for supportive evidence from large scale randomised placebo-controlled trials (RCTs); four such studies are currently underway in the USA. Alzheimer s Disease Alzheimer s Disease accounts for a large proportion of all cases of dementia. There has been a growing interest in factors that may underlie this debilitating disease. It is now

8 recognised that people with cardiovascular risk factors and a history of stroke have an increased risk of some types of dementia, including Alzheimer s disease. For example, elevated homocysteine levels have been shown to be associated with risk of Alzheimer s disease. Again, work is under way that is attempting to establish whether risk might be influenced by nutrient intake. How much folate are people consuming? A European review of folate intakes in a range of countries found that average total intakes of folate from all sources ranged from 168 µg/day to 326 µg/day. The highest intake was recorded in France (Paris area) and the lowest in Irish, British, and Swedish women and in Irish men over 40 years of age. Differences in intake partly reflect differences in dietary patterns, in particular consumption of vegetables, fruit and grains. Among women in the UK, the average intake from food among those aged years is 250 µg/day. The average intake including supplements is also below 400 µg/day, despite recommendations for women of childbearing age to take folic acid supplements (see Table 2). As can be seen from Table 2, the highest average intakes of folate/folic acid are to be found among the older women (50-64 years), who are unlikely to benefit from folate s effect on NTDs. Table 2. Folate intakes among women in the UK Women (age) Intake from food (µg/day) Intake from all sources (µg/day 15-18* All (19-64) Source: Henderson et al. 2003; * Gregory et al There is also some evidence of low folate status among teenage girls in a number of European countries, including Spain and Ireland. In the UK, about 40% of year olds were found to have marginal folate status. Poor folate status is also common among older people (65 years and over), and in the UK especially among those living in institutions (Figure 2).

9 Figure 2. Folate status of Elderly People in the UK 20% % respondents 16% 12% 8% 4% 0% Free-living elderly Elderly people living in institutions Severe deficiency Marginal status Folate status Source: Finch et al Ways to increase folate intake Folate intake can be increased by a number of routes. Firstly, it is possible to increase consumption of foods naturally rich in folate such as leafy vegetables, fruits and berries, beans, whole grain products and liver. As folate is sensitive to heat, vegetables should be served raw or only gently cooked (e.g. steamed). Folate intake can also be increased by eating more folic acid fortified foods, such as breakfast cereals, more often or in greater amounts. However, folic acid fortification is not permitted in some parts of the EU. Other options for increasing intakes include the use of folic acid supplements, as well as the option of national fortification programmes for selected foods through which folic acid is added by law, as currently occurs in the USA, Canada and Chile. Governments in various EU countries, e.g. the UK and the Netherlands, have considered whether fortification of flour should become law. Despite positive recommendations from scientific advisory committees, to date no EU country has taken this step, largely because of concerns about safety, in particular the concerns related to vitamin B 12 deficiency. In the search for new options, the EU-funded FolateFuncHealth project has been examining the opportunities to enhance the amount of folate present in folate-containing foods (see below). Safety Folic acid is a water soluble vitamin so the body can normally get rid of excess amounts quite easily. It is, therefore, generally considered safe, even at amounts of mg/day. For guidance, a safe upper level of folic acid intake has been set at 1000 µg/day. However, adverse effects of supplementation may occur in people being treated with drugs that interfere with folate metabolism (e.g. specific anti-cancer drugs) and individuals at risk of vitamin B 12 deficiency (typically elderly people). It has been

10 estimated that 127 people per million in the UK have vitamin B 12 deficiency anaemia, which if untreated can lead to peripheral nerve damage in the extremities (e.g. the feet). High levels of folate intake may mask vitamin B 12 deficiency anaemia to the point that diagnosis of B 12 deficiency is delayed, leading to permanent nerve damage. It is therefore critical to have adequate intakes of both nutrients. It is important to note that the long-term biological effects of exposure to folic acid, the man-made form of folate, still need to be established. Although the body metabolises folic acid to a form of the vitamin that can be transported in the blood, this process seems to work only at doses of up to about 400 µg/day. At higher doses, it is assumed that the unmodified folic acid remains in the blood; the impact of this on long term health needs consideration. Folate Research in Europe The FolateFuncHealth project was funded by the European Union under the Quality of Life Programme, one of the four thematic programmes of the Fifth Framework Programme of research. This project has focused on folate and folic acid, with an overall aim to provide folate-rich and enriched-foods with specified and scientifically-verified consumer benefits for optimal bioavailability, function and health. Work has included looking at: 1. the use of folate-producing bacteria and yeast to increase the folate content of fermented foods (e.g. bread, dairy products, beer); 2. the effect of processing (e.g. dough making, fermentation, baking and brewing) on folate; 3. the identification/selection of high-folate ingredients; 4. the health effects of folate-rich foods compared to those foods fortified with folic acid; and 5. suitable foods for folic acid fortification. Key outputs of FolateFuncHealth: Better information is now available on the amounts of food folates present in raw materials and processed foods, for use in food composition tables and for food labelling purposes. The natural folate content of fermented foods (e.g. bread yogurts, beer) can be improved by careful selection of the fermentation conditions and the nature of the bacterial or yeast culture used, e.g. the type of yeast used to make bread. Improvements can also be made by careful combination of the steps in the fermentation process and by optimising malting and germination conditions. For example, the folate content of beer can be increased by careful selection of raw materials (malt) and changes in the brewing process. Compared to traditional high temperature sterilisation processes, some methods of food preservation such as mild pasteurisation and high pressure treatments, can reduce folate losses by up to 50% in soups, beverages and fruit juices. Improved selection of raw materials and other ingredients (e.g. herbs) may increase folate levels up to two-fold in rye bread, fermented dairy foods and

11 soups. For example, with rye bread, a major staple in Northern Europe, folate levels in the finished product can be improved by selecting folate-rich varieties of grain, improving folate stability, minimising folate losses by selection of processing conditions, and enhancing folate content by attention to the fermentation process (e.g. sour dough fermentation). In terms of foods for folic acid fortification, milk (both pasteurised and UHT) was shown to be a potentially suitable candidate. Further details can be found at Conclusions Folate status is now recognised as being potentially important to health in the context of a number of chronic diseases. For example, lower folate status has been associated with a greater risk of heart disease, some cancers and Alzheimer s disease, but direct cause and effect has still to be established for each of these. Strong evidence already exists that supplementation with folic acid can prevent neural tube defects in the developing fetus. Although women of child-bearing age are encouraged to take folic acid supplements (400 µg/day), many women do not, missing the critical window (the first 12 weeks) for the prevention of neural tube defects. Increasing folate intake to the required level through folate-rich foods alone would be very difficult if not impossible to achieve, as it would require a three fold increase of current dietary folate intakes. Fortified foods (e.g. some breakfast cereals) offer an opportunity to increase intakes, while mandatory fortification of the food supply, such as has already been introduced in the USA, Canada and Chile, appears to be an effective approach. However, fortification of the food supply remains controversial because of the uncertainty of the long term effects and the adverse consequences it may have in other groups of the population, in particular elderly people at risk of vitamin B 12 deficiency. In the absence of fortification programmes, further research is needed to identify successful approaches to increasing folic acid intakes. The EU-funded FolateFuncHealth project on folate has made significant contributions to this area.

12 FolateFuncHealth Projects Details of the different projects, project leaders and contact details are given below. Food Composition & Intake Project leader: Prof Vieno Piironen, Department of Applied Chemistry & Microbiology, University of Helsinki, Finland Tel: Fax: Food Folates Project leader: Paul Finglas, Institute of Food Research, Norwich Research Park, Colney, Norwich, NR4 7UA, United Kingdom Tel: Fax: Processing Effects Project leader: Prof Margaretha Jägerstad, Department of Food Science, Swedish University of Agricultural Sciences, Uppsala, Sweden Tel: Fax: Bioavailability (in vitro in laboratory conditions) Project leader: Dr Trinette van Vliet, TNO Nutrition and Food Research Institute, Zeist, the Netherlands Tel: Fax: Bioavailability (in vivo in humans) Project leader: Paul Finglas, Institute of Food Research, Norwich Research Park, Colney, Norwich, NR4 7UA, United Kingdom Tel: Fax: Project leader: Prof Margaretha Jägerstad, Department of Food Science, Swedish University of Agricultural Sciences, Uppsala, Sweden Tel: Fax: Bioactivity & Functionality Project leader: Paul Finglas, Institute of Food Research, Norwich Research Park,

13 Colney, Norwich, NR4 7UA, United Kingdom Tel: Fax: Effects of age, genotype and form of folate on absorption & retention by the body cells Project leader: Prof Klaus Pietrzik, Institute of Nutritional Science, University of Bonn, Germany Tel: Fax: Project leader: Dr Trinette van Vliet, TNO Nutrition and Food Research Institute, Zeist, the Netherlands Tel: Fax:

14 Further reading Brzozowska, A, Finglas, PM, Wright, D & Araucz, M, Eds. First International Conference on Folates - Analysis, Bioavailability and Health. Warsaw: Warsaw Agricultural University Press [ISBN ]. De Bree A, van Dusseldorp M, Brouwer IA, van het Hof KH, Steegers-Theunissen RPM (1997) Folate intake in Europe: recommended, actual and desired. European Journal of Clinical Nutrition 51: Health Education Authority (1998a) Changing Perceptions, Volume 1. The HEA Folic Acid Campaign Summary Report. HEA, London. Health Education Authority (1998b) Changing Perceptions, Volume 1. The HEA Folic Acid Campaign Research Report. HEA, London Henderson L et al (2003) The National Diet and Nutrition Survey: Adults Aged years, Volume 3: Vitamin and Mineral Intake and Urinary Analysis. London, HMSO. Gregory J, Lowe S, Bates C J, Prentice A, Jackson L V, Smithers G, Wenlock R and Farron, M (2000) National Diet and Nutrition Survey: Young people aged 4-18 years. The Stationery Office, London Wald NJ (2004) Folic acid and the prevention of neural tube defects. New England Journal of Medicine 35, Wild J, Sutcliffe M, Schorah CJ, Levene MI (1997) Prevention of neural tube defects. Lancet 350,

15 Glossary Bioavailability refers to the actual amount of a substance, for example a nutrient such as folate, which is available to the body for use. DNA (or deoxyribonucleic acid) is a double-stranded molecule that encodes genetic information in the nucleus of cells. Folate is one of the B vitamins. Folate status is usually determined by measuring serum folate or red cell folate, which is a better indicator of long term status. This is more accurate than relying solely on nutrient intake data. Folic acid is the man-made or synthetic form of folate. Homocysteine is an amino acid. High amounts of homocysteine in the blood is a risk factor for heart disease. Megaloblastic anaemia is a type of anaemia caused by folate deficiency. This type of anaemia is characterised by very large red blood cells. Neural tube defects (NTDs) are among the most significant congenital causes of illness and death in infants. Examples of NTDs include spina bifida, anencephaly and encephalocele. Nutrients are components of food that cannot be made by the body but are required for normal growth and development. RCTs (or randomised controlled trials) are a type of study design. In RCTs participants are randomly assigned to two or more groups: at least one (the experimental group) receiving an intervention that is being tested and another (the comparison or control group) receiving an alternative treatment or no treatment. This design allows the effect of the intervention to be compared. RNA (or ribonucleic acid) plays a role in transferring information from DNA to the protein-forming system of the cell. Vitamins are a group of nutrients needed by the body in very small amounts. Vitamins are normally divided into those which are water soluble (e.g. folate) and those which are fat soluble (e.g. vitamin A).

16 A project funded by the European Union under key Action 1: Food, Nutrition and Health QLRT & QLRT