Folates dietary intake levels

Various studies have suggested that a generous intake of folate and B vitamins may be beneficial in stroke prevention by reducing the level of plasma Hey (Robinson et al. 1998). The association between dietary intake of folate and the subsequent risk of stroke and cardiovascular disease (CVD) is well documented. 

While observational studies had reported inverse associations of dietary intake of folate (or blood levels of folate) with overall risks of cancer, colorectal cancer or breast cancer (Giovannucci et al. 2002 Larsson et al. 2007 Lin et al. 2008 Zhang et al. 2003), one small trial involving 1021 individuals with a prior history of colorectal adenoma suggested a possible adverse effect on both the risk of recurrent colorectal adenoma (Cole et al. 2007) and on prostate cancer... 

Many patients with infection have a reduced serum level of folate, particularly those with chronic bacterial infections. However, the development of a megaloblastic anemia is uncommon and when it does occur is perhaps more often associated with the treatment. It is probable that the folate deficiency is the result of a combination of fiictors including poor dietary intake, low reserves, an increased demand due to an increased cell turnover, impaired absorption, vomiting, and impaired metabolism due to the toxic state of the patient (C17, M16, W25). Pyrexia may also inhibit the reduction of folate. Panders and Rupert (P13) found that if folic acid was incubated with a chicken liver enzyme preparation at an elevated temperature the reduction of folic acid to tetrahydrofolic acid was inhibited. 

The importance of red cell folate determinations in certain diagnoses of folate deficiency has been clearly established. Erythrocyte folate levels are good indicators of tissue folate stores, whereas serum folate levels are poor indicators since they reflect recent dietary intake and often provide little useful clinical information 37-34). For example, serum folate levels fall promptly after transient periods of dietary deprivation and remain abnormally low for weeks or months before red cell folate levels fall. In contrast, the fall in red cell folate immediately precedes the clinical and hematologic manifestation of folate deficiency (42). 

Sources Dietary Reference Intakes for Calcium, Phosphorous, Magnesium, Vitamin D, and Huoride (1997) Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin 85, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline (1998) EHetary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids (2000) Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc (2001) Dietary Reference Intakes for Water, Potassium, Sodium, Chloride, and Sulfate (2005) and EHetary Reference Intakes for Calcium and Vitamin D (2011). These reports may be accessed via www.nap.edu A Tolerable Upper Intake Level (UL) is the highest level of daily nutrient intake that is likely to pose no risk of adverse health effects to almost all individuals in the general population. Unless otherwise specified, the UL represents total intake from food, water, and supplements. Due to a lack of suitable data, ULs could not be established for vitamin K, thiamin, riboflavin, vitamin B12, pantothenic acid, biotin, and carotenoids. In the absence of a UL, extra caution may be warranted in consuming levels above recommended intakes. Members of the general population should be advised not to routinely exceed the UL. The UL is not meant to ply to individuals who are treated with the nutrient under medical supervision or to individuals with predisposing conditions that modify their sensitivity to the nutrient... 

Dietary folate intake determines folate nutritional status. It is therefore important to accurately measure folate in food using the best analytical platform currently available. In particular, folate analysis is confounded by several factors, such as the presence of many vitamers, low concentrations, physicochemical instability, and complex sample preparation [12]. It has been reported that the levels of endogenous 5-methyltetrahydrofolate and 5-formyltetrahydrofolate in canned chickpeas, a rich folate source, were 52 and 8 pg/lOO g, respectively [13]. Folate-fortified foods contain higher total folate concentrations than those found in natural folate-rich foods. We recently determined folic acid in Australian fortified bread varieties that was approximately 100 [tg/100 g [14]. 

Folate can be measured in plasma or serum by microbiological assay using L. casei as the test organism, but this test can be confounded if the subject is on antibiotic treatment. Serum folate values reflect recent dietary intake and a vitamin deficiency is ascribed only where serum folate remains low over a period of time. Plasma folate levels are thought to reflect the day-to-day variations in dietary folate levels while red blood cell folate is a better indicator of long-term tissue storage levels. 

Folate deficiency is most likely to occur in patients on long-lasting AED therapy. Furthermore, folate concentrations are inversely related to the number of prescribed AEDs. Patients on combinations of two or more AEDs tend to have lower folate levels than patients on monotherapy. Combinations of AEDs may have synergistic effects on folate absorption and/or metabolism. Moreover, the dietary intake of B vitamins tends to decrease with an increasing number of AEDs. Patients on combination therapy tend to a have more severe epilepsy, often associated with other neurological deficits and may even need to live in institutions. 

The amount of foHc acid required for daily intake is estimated based on the minimum amount required to maintain a certain level of semm folate. The recommended dietary allowance (RDA) for foHc acid accounts for daily losses and makes allowances for variation in individual needs and bioavailabiHty from food sources (85). The U.S. recommended daily allowance for adults is 400 )Ug and for pregnant women is 800 X (Table 4). 

Standing Committee on the Scientific Evaluation of Dietary Reference Intakes and its Panel on Folate, other B vitamins, and Choline and Subcommittee on Upper Reference Levels of Nutrients. Dietary reference intakes for thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin, and choline. Washington DC National Academy Press, 1998. 

It is of paramount importance to rule out vitamin B12 deficiency when folate deficiency is detected, as symptoms are similar. Laboratory changes associated with folate deficiency are similar to those seen in vitamin Bn deficiency, except vitamin Bn levels are normal. Decreases occur in the serum folate level (<3 ng/mL) within a few days of dietary folate limitations. The RBC folate level (<150 ng/mL) also declines and may be a better indicator of deficiency, as levels remain constant throughout the life span of the erythrocyte. Serum folate levels are sensitive to short-term changes such as dietary restrictions or alcohol intake, which may result in a short-term decline in serum levels with adequate tissue stores. It should be noted that an estimated 60% of patients with pernicious anemia have falsely low RBC folate levels, in all probability due to the requirement of cobal-amin for the normal transfer of methyltetrahydrofolate from plasma to cells. Additionally, if serum or erythrocyte folate levels are borderline, serum homocysteine is usually increased with a folic acid deficiency. If serum MMA levels are also elevated, vitamin B12 deficiency needs to be ruled out. 

An increased plasma level of homocysteine is regarded as a risk factor for cardiovascular disease and the development of arteriosclerosis. Homocysteine concentrations in plasma are reduced by remethylation and transsulfuration (Komarnisky et al. 2003). The remethylation is catalyzed by methionine synthase, which in turn is influenced by vitamin B12 and folate. The transsulfura-tions depend on cystathionine 3-synthase. A dietary deficiency of vitamins B, B12 and folate, accompanied by a high protein intake, can cause hyperhomocystinemia in humans (Jacobsen 1998). Furthermore, a genetic disorder of enzymes involved in the metabolism of homocysteine leads to hypercystinuria (Mudd et al. 1989). 

The mechanisms by which vitamins prevent illnesses are not weU understood, and the amounts needed to lower risks for certain disease conditions may be higher than the current recommended levels for preventing nutritional deficiencies. For example, the Institute of Medicine recommends that to prevent neural tube birth defects, women of child-bearing age should consume 400 Xg of folic acid per day (but not more than 1000 Xg/day) from fortified foods and/or dietary supplements in addition to folates obtained from a varied diet. " < Ascorbic acid intakes of 80-200mg daily (8-20 times the amounts needed to prevent scurvy) may be necessary to enhance certain physiological functions and minimize specific disease risks. " ... 

Tree nuts can be good dietary sources (>10% of recommended dietary allowances [RDA] or adequate intake [Al]) of most vitamins except vitamins A and cobalamin (B,2). At suggested consumption level (1.5 ounces or 42.5g/day), acorn and pine nuts are excellent sources of folate and vitamin K (Table 2.7). In case of thiamin (Bj), niacin (B3), and pyridoxine (Bg), tree nuts offer alternative sources of these vitamins when more abundant animal sources are not available or are not consumed. 

---