Ординатура / Офтальмология / Английские материалы / Nutrition and the Eye Basic and Clinical Research_Augustin_2005

ascorbigen A (B) that is split into L-ascorbic acid in the course of cooking. However, thermal treatment usually destroys a considerable part of vitamin C.

Function

There are many functions related to vitamin C. It is required for the synthesis of collagen and also plays an important role in the syntheses of norepinephrine and carnitine [1]. Recent research also suggests that vitamin C is involved in the metabolism of cholesterol to bile acids [2].

Vitamin C is a highly effective antioxidant and can protect proteins, lipids, carbohydrates, and nucleic acids from damage by free radicals and reactive oxygen species that can be generated during normal metabolism as well as through exposure to toxins and pollutants. Vitamin C may also be able to regenerate other antioxidants, such as vitamin E [1].

However, vitamin C can interact in vitro with some free metal ions to produce potentially damaging free radicals. Although free metal ions are not generally found under physiological conditions, the idea that high doses of vitamin C might be able to promote oxidative damage in vivo has received a great deal of attention. A recent review found no sufficient scientific evidence that vitamin C promotes oxidative damage under physiological conditions or in humans [3].

Deficiency

Severe vitamin C deficiency has been known for many centuries as the disease scurvy. By the late 1700s the British navy was aware that scurvy could be cured by eating oranges or lemons, even though vitamin C would not be isolated until the early 1930s. At present, scurvy is rare in developed countries because it can be prevented by as little as 10 mg of vitamin C daily.

In the USA, the recommended dietary allowance (RDA) for vitamin C was revised upward from 60 mg daily for men and women (table 2). The recommended intake for smokers is 35 mg/day higher than for non-smokers, because smokers are under increased oxidative stress and generally have lower blood levels of vitamin C [4].

Disease Prevention

Much of the information regarding vitamin C and the prevention of chronic disease is based on prospective studies in which vitamin C intake is assessed in large numbers of people who are followed over time to determine whether they develop specific chronic diseases.

Cardiovascular Diseases

Until recently, the results of most studies indicated that low or deficient intakes of vitamin C were associated with an increased risk of cardiovascular

Table 2. RDA for vitamin C in the USA

diseases and that modest dietary intake of about 100 mg/day was sufficient to reduce the risk among non-smoking men and women [1]. Several studies failed to find significant reductions in the risk of coronary heart disease (CHD) among vitamin C supplement users [5, 6]. The First National Health and Nutrition Examination Study (NHANES I) [7] found that the risk of death from cardiovascular diseases was 42% lower in men and 25% lower in women who consumed50 mg/day of dietary vitamin C [8]. Recent results from the Nurses’ Health Study based on the follow-up of more than 85,000 women over 16 years also suggest that higher vitamin C intakes may be cardio-protective [9]. In this study, vitamin C intakes of 300 mg/day from diet plus supplements or supplements were associated with a 27–28% reduction in CHD risk. However, in those women who did not take vitamin C supplements, dietary vitamin C intake was not significantly associated with CHD risk. This finding is inconsistent with data from numerous other prospective cohort studies that found inverse associations between dietary vitamin C intake of vitamin C plasma levels and CHD risk [1, 10]. Data from the National Institutes of Health (NIH) indicated that plasma and circulating cells in healthy, young subjects became fully saturated with vitamin C at a dose of 400 mg/day [11]. The results of the NHANES I study and the Nurses’ Health Study suggest that maximum reduction of cardiovascular disease risk may require vitamin C intakes high enough to saturate plasma and circulating cells, and thus the vitamin C body pool [12].

Cancer

From a number of studies it has been concluded that increased consumption of fresh fruits and vegetables is associated with a reduced risk of several

types of cancer [13]. Such studies are the basis for dietary guidelines which recommend at least 5 servings of fruits and vegetables per day.

In several case-control studies the role of vitamin C in cancer prevention has been investigated. Most have shown that higher intakes of vitamin C are associated with a decreased incidence of several cancers. In general, prospective studies in which the lowest intake group consumed 86 mg of vitamin C daily have not found differences in cancer risk, while studies finding significant cancer risk reductions found them in people consuming at least 80–110 mg of vitamin C daily [1].

Although most large prospective studies found no association between breast cancer and vitamin C intake, two recent studies described dietary vitamin C intake to be inversely associated with breast cancer risk in certain subgroups [14]. In the Swedish Mammography Cohort, women who consumed an average of 110 mg/day of vitamin C had a 39% lower risk of breast cancer compared to women who consumed an average of 31 mg/day [15]. A number of observational studies have found increased dietary vitamin C intake to be associated with decreased risk of stomach cancer, and laboratory experiments indicate that vitamin C inhibits the formation of carcinogenic compounds in stomach. Infection with Heliobacter pylori is known to increase the risk of stomach cancer and also appears to lower the vitamin C content of stomach secretions. Although two intervention studies did not find a decrease in the occurrence of stomach cancer with vitamin C supplementation [4], more recent research suggests that vitamin C supplementation may be a useful addition to standard H. pylori eradication therapy in reducing the risk of gastric cancer [16].

Cataracts

Decreased vitamin C levels in the lens of the eye have been associated with increased severity of cataracts in humans. Some, but not all studies have observed increased dietary vitamin C intake [17] and increased blood levels of vitamin C [18] to be associated with decreased risk of cataracts. Those studies that have found a relationship suggest that vitamin C intake may have to be 300 mg/day for a number of years before a protective effect can be detected [1]. Recently, a 7-year controlled intervention trial of a daily antioxidant supplement containing 500 mg of vitamin C, 400 IU of vitamin E, and 15 mg of -carotene in 4,629 men and women found no difference between the antioxidant combination and a placebo on the development and progression of age-related cataracts [19]. Therefore, the relationship between vitamin C intake and the development of cataracts requires further clarification.

Table 3. Tocopherols and tocotrienols

Safety

A number of possible problems with very large doses of vitamin C have been suggested, mainly based on in vitro experiments or isolated case reports, including: genetic mutations, birth defects, cancer, atherosclerosis, kidney stones, ‘rebound’ scurvy, increased oxidative stress, excess iron absorption, and vitamin B12 deficiency. However, none of these adverse health effects have been confirmed, and there is no reliable scientific evidence that large amounts of vitamin C are toxic or detrimental to health. With the latest RDA published in 2000, a tolerable upper intake level (UL) of 2 g daily was recommended [4].

Vitamin E

The term vitamin E comprises a family of several antioxidants, i.e. tocopherols and tocotrienols (cf. formula and table 3). -Tocopherol is the only form of vitamin E found in the largest quantities in the blood and tissue [20]. As -tocopherol is the form of vitamin E that appears to have the greatest nutritional signif icance, it will be the primary topic of the following discussion.

Table 4. Amounts of vitamin E in selected foods (mg/100 g)

cells. In addition, -tocopherol has been shown to inhibit platelet aggregation and to enhance vasodilation [21, 22].

-Tocopherol

The function of -tocopherol in humans is still unclear. Its blood levels are generally 10 times lower than those of -tocopherol. Limited in vitro and animal tests indicate that -tocopherol or its metabolites may play a role in the protection of the body from damage of free radicals [23, 24], however these effects have not been demonstrated convincingly in humans.

In one recent prospective study increased plasma -tocopherol levels were associated with a significantly reduced risk of developing prostate cancer, while significant protective associations for increased levels of plasma -tocopherol were found only when -tocopherol levels were also high [25]. These limited findings, in addition to the fact that taking -tocopherol supplements may lower-tocopherol levels in blood, have activated the interest for additional research on the effects of dietary and supplemental -tocopherol on health [26].

Deficiency

Vitamin E deficiency has been observed in individuals with malnutrition, genetic defects affecting the -tocopherol transfer protein and fat malabsorption syndromes. Severe vitamin E deficiency results mainly in neurological symptoms (ataxia and peripheral neuropathy), myopathy, and pigmented retinopathy. For this reason, people who develop peripheral neuropathy, ataxia or retinitis pigmentosa should be screened for vitamin E deficiency [27].

Table 5. RDA for (RRR)- -tocopherol in the USA

Although true vitamin E deficiency is rare, suboptimal intake of vitamin E is quite common. The National Health and Nutrition Examination Survey III (NHANES III) investigated the dietary intake and blood levels of -tocopherol in 16,295 multi-ethnic adults. 27% of white participants, 41% of AfricanAmericans, 28% of Mexican-Americans and 32% of the other participants were found to have blood levels of -tocopherol 20 mol/l, a value chosen because the literature suggests an increased risk for cardiovascular disease below this level [28].

The RDA for vitamin E was previously 8 mg/day for women and 10 mg/day for men, but it was revised in 2000 [21] (table 5).

Disease Prevention

Cardiovascular Diseases

The results of large observational studies suggest that increased vitamin E consumption is associated with decreased risk of myocardial infarction or death from heart disease in both men and women. Each study was a prospective study which measured vitamin E consumption in presumably healthy people and followed them for number of years to determine how many of them were diagnosed with, or died as a result of heart disease. In two of the studies, those individuals who consumed 7 mg of -tocopherol in food were only approximately 35% as likely to die from heart disease as those who consumed 3–5 mg of-tocopherol [29, 30]. Two other large studies found a significant reduction in the risk of heart disease only in those women and men who consumed -tocopherol supplements of at least 67 mg of (RRR)- -tocopherol daily [31, 32]. Recently, several studies have observed plasma or red blood cell levels of -tocopherol to

be inversely associated with the presence or severity supplements in patients with heart disease have not shown vitamin E to be effective in preventing heart attacks or death [33, 34].

Cancer

Several large prospective studies have failed to find significant associations between -tocopherol intake and the incidence of lung cancer or breast cancer [21]. A placebo-controlled intervention study designed to look at the effect of -tocopherol supplementation on lung cancer in smokers found a 34% reduction in the incidence of prostate cancer in smokers given supplements of 50 mg of synthetic -tocopherol (equivalent to 25 mg of (RRR)- -tocopherol) daily [35].

Cataracts

To date, ten observational studies have examined the association between vitamin E consumption and the incidence and severity of cataracts. Of these studies, five found increased vitamin E intake to be associated with protection from cataracts, while five reported no association [36, 37]. A recent intervention trial of a daily antioxidant supplement containing 500 mg of vitamin C, 400 IU of vitamin E, and 15 mg of -carotene in 4,629 men and women found that the antioxidant supplement was not different than a placebo in its effects on the development and progression of age-related cataracts over a 7-year period [38]. Another invention trial found that a daily supplement of 50 mg of synthetic -tocopherol daily (equivalent to 25 mg (RRR)- -tocopherol) did not alter the incidence of cataract surgery in male smokers [39]. Thus, the relationship between vitamin E intake and the development of cataracts requires further clarification.

Immune Function

-Tocopherol has been shown to enhance specific aspects of the immune response. For instance, 200 mg of synthetic -tocopherol (equivalent to 100 mg (RRR)- -tocopherol) daily for several months increased the formation of antibodies in response to hepatitis B vaccine and tetanus vaccine in elderly adults [40]. Whether -tocopherol-associated enhancements in the immune response actually translate to increased resistance to infections in older adults remains to be determined [41].

Safety

Few side effects have been noted in adults taking supplements of 2,000 mg of -tocopherol daily ([RRR]- or racemic -tocopherol). However, results of long-term -tocopherol supplementation have not been studied. In addition

Table 6. Tolerable UL for -tocopherol in the USA

to setting the new RDA for -tocopherol in 2000, an upper limit (UL) for-tocopherol was given (table 6). An UL of 1,000 mg daily of -tocopherol of any form would be the highest dose unlikely to result in potential hemorrhage in adults [21].

Copper

Copper (Cu) is an essential trace element for animals and humans. In the body, copper shifts between the cuprous (Cu1 ) and the cupric (Cu2 ) forms, though the majority of the body’s copper is in the Cu2 form. The ability of copper to easily accept and donate electrons explains its important role in oxidoreductions and scavenging of free radicals [42].

Food Sources

Copper is found in a wide variety of foods and is most plentiful in organ meats, shellfish, nuts, and seeds. Wheat bran cereals and whole grain products are also good sources of copper. According to national surveys, the average dietary intake of copper in the USA is approximately 1.0–1.1 mg/day for adult women and 1.2–1.6 mg/day for adult men.

Function

Copper is a critical functional component of a number of essential enzymes. Some of the physiological functions known to be copper-dependent are discussed below.

Cytochrome c oxidase plays an essential role in cellular energy production. By catalyzing the reduction of molecular oxygen to water, an electrical gradient is generated used by the mitochondria to create ATP [43].