Intakes tocopherols

Due to bleeding risk, individuals on anticoagulant therapy or individuals who are vitamin K-deficient should not take vitamin E supplementation without close medical supervision. Absent of that, vitamin E is a well-tolerated relatively non-toxic nutrient. A tolerable upper intake level of 1,000 mg daily of a-tocopherol of any form (equivalent to 1,500 IU of RRR a-tocopherol or 1,100 IU of all-rac-a-tocopherol) would be, according to the Food and Nutrition Board of the Institute of Medicine, the highest dose unlikely to result in haemorrhage in almost all adults. 

No unequivocal unique function for vitamin E has been defined. However, it does act as a hpid-soluble antioxidant in cell membranes, where many of its functions can be provided by synthetic antioxidants. Vitamin E is the generic descriptor for two famihes of compounds, the tocopherols and the tocotrienols (Figure 45—5). The different vitamers (compounds having similar vitamin activity) have different biologic potencies the most active is D-a-tocopherol, and it is usual to express vitamin E intake in milhgrams of D-a-tocoph-erol equivalents. Synthetic DL-a-tocopherol does not have the same biologic potency as the namrally occurring compound. 

It is well known that excessive intake of P-carotene may lead to carotenodermia (yellow skin), and it is undoubtedly the case that some carotenoid is directly lost via the skin or through photo-oxidation in the skin. As far as is known the carotenoids are not cytotoxic or genotoxic even at concentrations up to 10 times the normal plasma concentration which may cause carotenodermia. However, they are associated with amenorrhoea in girls who may be consuming bizarre diets and, in long-term supplementation studies, with an increase in lung cancer (The Alpha-tocopherol, Beta-carotene Cancer Prevention Study Group, 1994). 

Deficiency of vitamin E is characterized by low serum tocopherol levels and a positive hydrogen peroxide hemolysis test. This deficiency is believed to occur in patients with biliary, pancreatic, or intestinal disease that is characterized by excessive steatorrhea. Premature infants with a high intake of fatty acids exhibit a deficiency syndrome characterized by edema, anemia, and low tocopherol levels. This condition is reversed by giving vitamin E. 

Table 6.4 summarizes the concentrations of a range of endogenous (i.e., nondietary) simple phenols, including a-tocopherol, and ascorbate in plasma from healthy individuals. The total simple phenol and ascorbate concentration is between 159 and 380 pM. The maximum additional concentration that is likely to be achieved from dietary sources, 3 to 22 pM, is marginal by comparison adding only between 0.3 and 5% if it is assumed, quite reasonably, that the typical mean intake is taken over three equal meals. Many people consume a much smaller quantity of dietary PPT and even those consuming double the... 

Vegetable oils are rich sources of vitamin E, whereas liver and eggs contain moderate amounts. The RDA for a-tocopherol is 10 mg for men and 8 mg for women. Vitamin E requirement increases as the intake of polyunsaturated fatty acid increases. 

Research Council defined 1 mg of a-tocopherol as 1 unit of a-TE (mg x 1). The activities as a-TE of other vitamers were (3-tocopherol, mg x 0.5 y-tocopherol, mg xO. 1 8-tocopherol, mg x 0.03 a-tocotrienol, mg x 0.3 and (3-to-cotrienol, mg x 0.05. The activities of y- and 8-tocotrienol were undetectable. The Recommended Dietary Allowances (RDAs) are only based on intake of the 2R-stereoisomeric forms of a-tocopherol (RRR-, RSR-, RRS-, and RSS-tocopherol) from food, fortified food, and vitamin supplements (Food and Nutrition Board, 2000). The 2S-stereoisomeric forms of a-tocopherol and the other tocopherols ((3-, y-, and 5-tocopherol) and tocotrienols are not used to estimate the RDAs. 

Supplementation with the antioxidant vitamins ascorbic acid (250 mg) and mixed natural tocopherols (50 IU on alternate days) may be beneficial. Higher doses may vitiate the impact of lipid lowering therapy. Other naturally occurring antioxidants such as resveratrol, 3-catechin, selenium, and various carotenoids found in a variety of fruits and vegetables may provide additional antioxidant defense. Homocysteine, which initiates proatherogenic changes in endothelium, can be reduced in many patients by restriction of total protein intake to the amount required for amino acid replacement. Daily supplementation with up to 2 mg of folic acid plus other B vitamins is also recommended. 

In a large trial (37) conducted in eight European countries— European Antioxidant Miocardial Infarction and Breast Cancer (EURAMIC) trial—the fatty acid composition, a-tocopherol, and /3-carotene levels were determined in adipose tissue of patients with acute Ml. The study supported the hypothesis that /3-carotene protects against Ml because it reduces the oxidation of PUFA. The concentration on adipose tissue was considered due to the dietary intake. 

A higher dosage of antioxidants or an increase of the intake of antioxidant with food was not modifying substantially the oxidative markers, despite a significant increase of a-tocopherol, carotenoids, and vitamin C in serum (92,93). 

I 90 Pietinen P Rimm EB, Korkonen R et al, Intake of dietary fiber and risk of coronary heart disease in a cohort of Finnish men. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Circulation 1996 94 2720-2727,... 

The feasibility of increasing the a-tocopherol concentration of milk by supplementation of the feed has been investigated in many studies (Dunkley et al., 1966, 1967 King et al., 1966 St. Laurent et al., 1990 Barrefors et al., 1995 Focant et al., 1998 Granelli et al., 1998). These studies showed that when feed was supplemented with varying levels of a-tocopheryl acetate, the a-tocopherol content of the milk was increased with consequent increased resistance to spontaneous and copper-induced oxidation. King et al. (1967) reported that when feed was supplemented to achieve an intake of 1 g a-tocopherol per day per cow, oxidation was effectively controlled in milk... 

Ravnskov (1998) presented data for 28 cohorts from 21 prospective studies. In only three of these cohorts did the evidence show that saturated fat was associated with a statistically significant increased risk of CHD. CHD patients in three cohort studies had consumed significantly more polyunsaturated fat, and in only one cohort had CHD patients eaten less polyunsaturated fat than CHD-free participants. The cohorts included the Framingham Study and the large well-conducted Health Professionals Follow-up Study and the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Since then, Hu et al. (1997) presented the 14-year follow-up data from the Nurses Health Study. After adjustment for confounding variables in multivariate analyses, no statistically significant associations were found between intake of total fat, animal fat, or saturated fat and the risk of CHD. 

Kritchevsky and Kritchevsky (2000) provided a summary of the evidence linking dietary cholesterol to the risk of CHD in 10 cohorts from eight large, well-conducted prospective studies that were reported since 1980, which included the Nurses Health Study, the Health Professionals Followup Study and the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. In eight of the cohorts there was no statistical association between cholesterol intake and the risk of CHD. In one of the positive studies the association was established by simple univariate analysis and was not adjusted for other dietary variables. The other study adjusted only for fat intake. There is no compelling evidence from these epidemiological studies that dietary cholesterol is associated with the risk of CHD. 

Early studies of the relation between intake of TFAs and the occurrence of CHD also produced conflicting results. However, the large, well-conducted prospective studies showed positive associations between TFA intake and risk of CHD. The Nurses Health Study and the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study produced statistically significant positive associations, whereas in the Health Professionals Followup Study the positive association did not attain statistical significance (Ascherio et al., 1999). There was also a significant positive association between TFA intake and CHD risk in the smaller Zutphen Elderly Study (Oomen et al., 2001). 

A case-control study (Ascherio et al., 1994), a cross-sectional study (Bolton-Smith et al., 1996) and three prospective studies the Nurses Health Study (Willett et al., 1993), the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (Pietinen et al., 1997), and the Zutphen Elderly Study (Oomen et al., 2001), separately assessed the effect of TFAs from hydrogenated vegetable oil and animal fat on the risk of CHD. With the exception of the small Zutpen Elderly Study (Oomen et al., 2001), the studies found that the positive association with the risk of CHD was explained entirely by the intake of TFAs from hydrogenated vegetable oil. 

The U.S./Canadian Dietary Reference intakes report (Institute of Medicine, 2000) departed from tradition by considering only the contribution of the 2R isomers to vitamin E intake, and proposed an equivalence of 0.45 iu per mg for synthetic all-rac-a-tocopherol, although in consideration of upper tolerable levels of intake (Section 4.6.1), they considered the contribution of aU isomers equally However, although the 2S isomers have a shorter half-life than -tocopherol in the circulation, and hence a lower apparent biological availability, they are active in animal biological assays (Hoppe and Krennrich, 2000). 

Vitamin E deficiency is not a problem, even among people living on relatively poor diets. In depletion studies, very low intakes of vitamin E must be maintained for many months before there is any significant fall in circulating a-tocopherol, because there are relatively large tissue reserves of the vitamin. 

Based on the plasma concentration of a-tocopherol to prevent significant hemolysis in vitro (14 to 16 /xmol per L), the U.S./Canadian estimated average requirement is 12 mg per day, giving a Recommended Dietary Amount (RDA) of 15 mg per day (Institute of Medicine, 2000) - a 50% increase on the previous RDA (National Research Council, 1989). This increase arose partly as a result of considering only the 2R isomers in dietary intake (Section 4.1). Average intakes are of the order of 8 to 12 mg of a -tocopherol equivalent per day it would be difficult meet this reference intake without significant changes in diet or use of supplements. 

The main metabolite of /-tocopherol is 2,7,8-trimethyl-2-(/3-carboxyeth-yl) -G-hydroxychromem (/ -CEHC), which is excreted in the urine. It heis potentially physiologically significant natriuretic activity, whereas the corresponding metabolite of a-tocopherol, which is formed in increasing amounts as intake increases, is inactive (Jiang et al., 2001). 

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