Vitamin C

Low plasma ascorbic-acid concentrations have been reported to be strongly predictive of mortality, particularly in men. Results of a prospective trial in the UK (EPIC-Norfolk Prospective Study), in which 19496 men and women aged 45-79 years were followed for 4 years, showed that men and women in the highest quintile of plasma ascorbic-acid concentration in samples collected within 1 year of entry into the study had significantly (p < 0.0001) lower all-cause mortality than those in the lowest quintile. Highest-quintile concentrations of plasma ascorbic acid (mean ± standard deviation) were 72.6 ± 11.5 mmoll"1 for men and 85.1 ± 13.7 mmolT1 for women; lowest quintiles were 20.8 ± 7.1 mmolT1 and 30.3 ± 10.1 mmolT1, respectively, for men and women. In men and women in the highest quintile, RRs (CI) for all-cause mortality were, respectively, 0.48 (0.33-0.70) and 0.50 (0.32-0.81), relative to those in the lowest quin-tile. Mortality from ischemic heart disease was also significantly (p < 0.001) lower in the highest quintiles: for men the RR (CI) was 0.32 (0.15-0.75), and for women it was 0.07 (0.01-0.67). The relationship held for CVD and cancer in men (p < 0.001), but no significant difference in cancer mortality was seen in women, and CVD rates in women were affected less than those in men. The mean ascorbic-acid level in

Table 1 Possible reasons for the conflict in results between observational epidemiological and supplementation trials

• Antioxidants are likely to work in cooperation with each other; more of one may increase the need for another

• The action of an antioxidant within a heterogeneous food matrix may be different from that in pure supplemental form

• A high intake of antioxidants may help to promote health when taken regularly over decades but may have little discernable effect over a few months or years

• A high intake of antioxidants may slow or even prevent some of the deleterious age-related changes that lead to chronic disease, but antioxidants are unlikely to reverse established pathological changes

• Benefits of increased antioxidant intake may be seen only in those with marginal or depleted antioxidant status at baseline

• The effect of antioxidant supplementation may be seen only in subgroups of the study population, e.g., in those individuals with certain single-nucleotide polymorphisms

• The key players may not be the most widely studied antioxidants; for example, 7-tocopherol, rather than a-tocopherol, may play an important role in modulation of cancer risk but has been little studied to date

• Antioxidants can act as pro-oxidants under certain conditions, and the net effect of a dietary antioxidant may well depend on dose and conditions at its site of action

• Antioxidant action per se may not be the key mechanism of action of protection; for example, immunomodulatory, anti-inflammatory, anti-proliferative, and pro-apoptotic effects of dietary agents (antioxidants or otherwise) may be more relevant to overall effects in terms of disease risk each quintile in women was around 10 mmoll-1 higher than that in men. Interestingly, the relationship between ascorbic-acid concentration and mortality was continuous throughout the range of plasma ascorbic-acid concentrations found. It was estimated that a 20 mmoll-1 increase in plasma ascorbic acid (achievable by one or two additional servings of fruit and vegetables each day) was associated with a 20% decrease in all-cause mortality, independent of age, blood pressure, cholesterol, smoking habit, and diabetes. Interestingly, also, mortality was not associated with supplement use, indicating that dietary sources of vitamin C are crucial.

In the Third National Health and Nutrition Examination Survey (NHANES III) in the USA, the plasma ascorbic-acid concentrations of 7658 men and women were not found to be independently associated with a history of cardiovascular disease in participants who reported no alcohol consumption; however, in 3497 participants who consumed alcohol a significantly lower prevalence of preexisting angina was found in those with high plasma ascorbic acid (>56 mmol l_1) than in those with 'low to marginal' levels (<22 mmoll-1). No significant association was seen between plasma ascorbic acid and previous myocardial infarction or stroke in this cross-sectional survey. In the NHANES II prospective study, a 43% decrease in mortality was associated with higher plasma ascorbic-acid levels in more than 3000 men followed for up to 16 years. Plasma ascorbic-acid levels in the highest and lowest quartiles in this study were more than 73 mmol l_1 and less than 28.4 mmoll-1, respectively. The corresponding values in women were again higher, at more than 85 mmoll-1 and less than 39.7 mmoll-1, respectively, and no significant relationship between plasma ascorbic-acid levels and mortality was seen in women.

The Kuopio IHD (ischemic heart disease) Risk Factor Study followed 1605 men for 5 years and reported an RR (CI) of 0.11 (0.04-0.30) for acute myocardial infarction in those men with higher plasma ascorbic-acid concentrations. The Medical Research Council Trial of Assessment and Management of Older People in the Community, a prospective trial in the UK of 1214 elderly subjects followed for a median of 4.4 years, showed that those in the highest quintile of plasma ascorbic-acid level (>66 mmoll-1) at entry had less than half the risk of dying in the follow-up period compared with those in the lowest quintile (plasma ascorbic-acid level of <17 mmoll-1). Data on men and women were not analyzed separately, but there were fewer men (27%) in the highest quintile of ascorbic-acid level. No relationship was seen between mortality and plasma levels or intake of ^-carotene or lipid-standardized a-tocopherol. Interestingly, while the relationship between mortality and the concentration of plasma ascorbic acid was strong, there was no significant association between mortality and estimated dietary intake of vitamin C. This may reflect the difficulty in obtaining accurate dietary information, but it also suggests that different individuals may well need different intakes to achieve certain plasma levels of ascorbic acid.

There have been many case-control and cohort studies performed in Europe and the USA and published in the past 15 years, and some data from Asia have been gathered. In most case-control studies no significant relationship has been demonstrated between intake and/or plasma ascorbic-acid levels and the risk of cardiovascular events; however, the combination of findings from individual studies is revealing. In a detailed analysis of 11 cohort studies comparing high and low intakes of ascorbic acid in 50 000 subjects overall, with 2148 CVD events during follow-up, a Peto's Odds Ratio (95% CI) of 0.89 (0.79-0.99) for CVD was calculated, indicating a modest reduction in risk associated with a high intake of vitamin C. In an analysis of five cohort studies comparing high and low plasma ascorbic-acid levels, involving 13 018 subjects overall with 543 CVD events during follow-up, a Peto's Odds Ratio for CVD of 0.58 (0.47-0.72) was calculated. This was interpreted as showing high plasma ascorbic-acid levels to be a powerful predictor of freedom from CVD during follow-up.

The relationship between antioxidant-rich diets and protection from cancer is strong and clear; however, the influences of individual antioxidants are difficult to isolate. Cancer risk increases as total calorie intake increases, and this confounds prospective and retrospective dietary studies. Cancer causes many biochemical changes, and cancer treatment is harsh, and this confounds the results of studies comparing antioxidant levels in plasma in cases and controls unless the samples were collected and analysed before cancer developed (which may be a considerable time before diagnosis). Currently, the evidence for a cancer-opposing effect of high intakes or plasma concentrations of ascorbic acid is conflicting. To date, the strongest evidence of a role for vitamin C in lowering cancer risk is in relation to cancer of the stomach, with a low intake of vitamin C being associated with a two-to-three-fold increase in the risk of stomach cancer. A Spanish study showed a 69% lower risk of stomach cancer in those in the highest quintile of vitamin C intake, and low levels of ascorbic acid in gastric juice are found in patients with chronic atrophic gastritis or Helicobacter pylori infection, both of which are associated with a greatly increased risk of gastric cancer. Whether the decrease in ascorbic acid is directly related to the development of gastric cancer is not known, but it is known that ascorbic acid inactivates carcinogenic nitrosamines within the stomach. There is also evidence of a decreased risk of cancer of the mouth, pharynx, pancreas, lung, cervix, and breast in association with increased vitamin C intake, though not all studies find this. it has been estimated that if the diets of postmenopausal women were enriched with vitamin C, a 16% decrease in breast cancer in these women would result. No significant association was reported between vitamin C intake and the incidence of ovarian cancer in 16 years of follow-up of 80326 women in the Nurses' Health Study. A study of 100 children with brain tumours showed a three-fold increase in risk in those children whose mothers had a low intake of vitamin C during pregnancy, suggesting that the dietary intake of vitamin C by pregnant women may help to determine the future cancer risk in their children. in a prospective study of 19496 British men and women aged 45-79 years and followed for 4 years (the EPiC (European Prospective investigation into Cancer and Nutrition) study), the RR (Ci) of mortality from cancer for a 20 mmol l"1 increase in plasma ascorbic acid was 0.85 (0.74-0.99). in men there was a strong and continuous decrease in cancer risk with increasing plasma ascorbic-acid concentrations, with an RR (Ci) in the highest quintile relative to the lowest quintile of 0.47 (0.27-0.88); i.e., the average risk in those with the highest plasma ascorbic-acid concentrations was less than half that of those in the lowest quintile. in women the decrease in RR did not reach statistical significance. The NHANES ii study reported that men in the lowest quartile of ascorbic-acid level had a 62% higher risk of death from cancer during 12 years of follow-up than those in the highest quartile. However, this relationship was not seen in women. Of possible relevance here is the common finding in these studies that men, in general, had lower ascorbic-acid levels than women.

Vitamin C is concentrated in ocular tissues and fluids, particularly in the anterior aspect (cornea and lens). A case-control study in Spain reported a 64% reduction in the risk of cataract (p < 0.0001) in those with a plasma ascorbic-acid concentration of more than 49 mmol l"1; however, no significant association with the dietary intake of vitamin C was seen. in a case-control study in the Netherlands, the prevalence of age-related maculopathy was reported to be twice as high in those with low anti-oxidant intake (from fruits and vegetables); however the data on vitamin C intake or plasma levels and maculopathy are conflicting. Lipid-soluble antioxidants, especially zeaxanthin and lutein (dietary-derived carotenoids that are highly concentrated in the lipid-rich fovea), may be more relevant in this condition than water-soluble vitamin C.

High plasma concentrations of ascorbic acid are reportedly associated with better memory performance, and lower plasma and cerebrospinal-fluid concentrations of ascorbic acid were found in patients with Alzheimer's disease than in non-demented controls. individuals who took vitamin C supplements were reported to have a lower prevalence of Alzheimer's disease on follow-up after 4.3 years. However, not all studies have shown a significant association between vitamin C intake or plasma levels and cognitive decline or dementia.

Breaking Bulimia

Breaking Bulimia

We have all been there: turning to the refrigerator if feeling lonely or bored or indulging in seconds or thirds if strained. But if you suffer from bulimia, the from time to time urge to overeat is more like an obsession.

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