Vitamin C in humans must be ingested for survival. Vitamin C is an electron donor, and this property accounts for all its known functions. As an electron donor, vitamin C is a potent water-soluble antioxidant in humans. Antioxidant effects of vitamin C have been demonstrated in many experiments in vitro. Human diseases such as atherosclerosis and cancer might occur in part from oxidant damage to tissues. Oxidation of lipids, proteins and DNA results in specific oxidation products that can be measured in the laboratory. While these biomarkers of oxidation have been measured in humans, such assays have not yet been validated or standardized, and the relationship of oxidant markers to human disease conditions is not clear. Epidemiological studies show that diets high in fruits and vegetables are associated with lower risk of cardiovascular disease, stroke and cancer, and with increased longevity. Whether these protective effects are directly attributable to vitamin C is not known. Intervention studies with vitamin C have shown no change in markers of oxidation or clinical benefit. Dose concentration studies of vitamin C in healthy people showed a sigmoidal relationship between oral dose and plasma and tissue vitamin C concentrations. Hence, optimal dosing is critical to intervention studies using vitamin C. Ideally, future studies of antioxidant actions of vitamin C should target selected patient groups. These groups should be known to have increased oxidative damage as assessed by a reliable biomarker or should have high morbidity and mortality due to diseases thought to be caused or exacerbated by oxidant damage.

Vitamin C as an Antioxidant: Evaluation of Its Role in Disease Prevention

The purpose of this evidence summary is to provide the best available information on the effect of anti-oxidants on mortality in patients with various diseases.

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Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases

Reactive oxygen species (ROS) influence many physiological processes including host defense, hormone biosynthesis, fertilization, and cellular signaling. Increased ROS production (termed "oxidative stress") has been implicated in various pathologies, including hypertension, atherosclerosis, diabetes, and chronic kidney disease. A major source for vascular and renal ROS is a family of nonphagocytic NAD(P)H oxidases, including the prototypic Nox2 homolog-based NAD(P)H oxidase, as well as other NAD(P)H oxidases, such as Nox1 and Nox4. Other possible sources include mitochondrial electron transport enzymes, xanthine oxidase, cyclooxygenase, lipoxygenase, and uncoupled nitric oxide synthase. NAD(P)H oxidase-derived ROS plays a physiological role in the regulation of endothelial function and vascular tone and a pathophysiological role in endothelial dysfunction, inflammation, hypertrophy, apoptosis, migration, fibrosis, angiogenesis, and rarefaction, important processes underlying cardiovascular and renal remodeling in hypertension and diabetes. These findings have evoked considerable interest because of the possibilities that therapies against nonphagocytic NAD(P)H oxidase to decrease ROS generation and/or strategies to increase nitric oxide (NO) availability and antioxidants may be useful in minimizing vascular injury and renal dysfunction and thereby prevent or regress target organ damage associated with hypertension and diabetes. Here we highlight current developments in the field of reactive oxygen species and cardiovascular disease, focusing specifically on the recently identified novel Nox family of NAD(P)H oxidases in hypertension. We also discuss the potential role of targeting ROS as a therapeutic possibility in the management of hypertension and cardiovascular disease.

https://care.diabetesjournals.org/content/diacare/31/Supplement_2/S170.full.pdf

NADPH oxidases, reactive oxygen species, and hypertension: clinical implications and therapeutic possibilities.

A comparison of the contribution of systolic versus diastolic blood pressure to risk of coronary heart disease and the role of mean arterial pulse pressure and systolic lability have been examined prospectively in 5,127 men and women during 14 years of biennial follow-up studies. Similar gradients of risk of subsequent coronary heart disease were observed whether persons were classified by their systolic or diastolic pressure, and no “safe” or critical level could be identified. Assessment of the net effect of each, employing discriminant analysis, indicated a stronger association of systolic than diastolic pressure with risk of coronary heart disease. Neither the systolic and diastolic pressure measurements in combination nor the pulse pressure and the mean arterial pressure measurements alone discriminated better than the systolic measurement alone. Systolic lability did not predict incidence of coronary heart disease independently of the associated level of blood pressure. There was a trend of declining relative importance of diastolic and a corresponding increase in the importance of systolic pressure with advancing age. Only in those under 45 was diastolic pressure predominant. The level of casually obtained blood pressure was a good predictor of coronary heart disease. The current practice of assessing the importance of blood pressure at all ages largely on the basis of diastolic pressure and the commonly held view concerning the innocuous nature of an elevated level of systolic pressure in the elderly requires reevaluation.

Systolic Versus Diastolic Blood Pressure and Risk of Coronary Heart Disease???The Framingham Study

OBJECTIVE: The aims of the present study were (1) to evaluate the degree to which underreporting of energy intake by repeated 24-hour recalls was related to gender, age, weight status, day of interview, educational level, smoking habits and area of living, and (2) to compare the dietary characteristics of underreporters with those of others. DESIGN: Cross-sectional study. Ten 24-hour recalls were performed during a one-year period. SETTING: The Vasterbotten intervention programme of cardiovascular disease and diabetes in Northern Sweden. SUBJECTS: Ninety-four men and 99 women in four age groups: 30, 40, 50 and 60 years. RESULTS: The prevalence of men and women with a food intake level (FIL; reported energy intake divided by estimated basal metabolic rate) below 1.2 was 44% and 47%, respectively. The youngest age group had higher FIL values than the oldest age group for both men (1.5 versus 1.1) and women (1.4 versus 1.1). The prevalence and magnitude of underreporting were directly related to body mass index (BMI; correlation coefficient: -0.47 (men) and -0.55 (women)). Smokers had a lower FIL value (1.1) than non-smokers (1.3). The nutrient density was lower for the group with high FIL values for protein and calcium and higher for fat and sucrose. The upper FIL group often had higher intake frequencies and larger portion sizes than the lower FIL group. CONCLUSIONS: Underreporting of energy intake is prevalent when 24-hour recalls are used, but the prevalence differs between sub-groups in the population. BMI was the main predictor of underreporting but also old age and smoking seem to contribute in this aspect. Socially desirable food items were not underreported to the same extent as socially undesirable food items. The intake frequencies and portion sizes partly explained the differences in FIL.

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Underreporting of energy intake in repeated 24-hour recalls related to gender, age, weight status, day of interview, educational level, reported food intake, smoking habits and area of living.

ObjectiveTo examine risk factors for poor iron status in British toddlers.DesignNational Diet and Nutrition Survey (NDNS) of children aged 1.5–4.5 years.SettingMainland Britain, 1992/93.SubjectsOf the 1859 children whose parents or guardians were interviewed, a weighed dietary intake was provided for 1675, and a blood sample obtained from 1003.ResultsMean haemoglobin (Hb) and ferritin levels were significantly lower in younger (1.5–2.5 years) than in older (3.5–4.5 years) children, with boys having significantly lower ferritin levels than girls. Poor iron status (Hb>110 g l−1, ferritin >10 μg l−1, or low values for both indices) was associated with lower socioeconomic and employment status. Iron status was directly associated with meat and fruit consumption and inversely with that of milk and milk products, after adjustment for age and gender. The latter association remained significant after further adjustment for sociodemographic variables, energy intake and body weight. Children consuming <400 g day−1 of milk and cream were less likely to consume foods in other groups, with those also consuming little meat, fish, fruit and nuts at greatest risk of poor iron status. Few associations were observed between poor iron status and individual nutrient intakes, and iron status was not associated with either iron intake or with consumption of a vegetarian diet.ConclusionsOverdependence on milk, where it displaces iron-rich or iron-enhancing foods, may put toddlers at increased risk of poor iron status. However, this becomes non-significant when moderate-to-high amounts of foods known to enhance iron status (e.g. meat and/or fruit) are also consumed. Milk consumption in this age group should ideally be part of a mixed and balanced diet including all food groups, and particularly lean meat (or other iron-rich or fortified foods) and fruit. This is particularly relevant for households of lower socioeconomic and employment status.

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Risk factors for poor iron status in British toddlers: further analysis of data from the National Diet and Nutrition Survey of children aged 1.5–4.5 years

OBJECTIVE To examine the relationships between alcohol consumption and a range of nutrient intakes and blood status indices in older people. DESIGN National Diet and Nutrition Survey: cross-sectional survey of nationally representative sample of people aged 65 years or over. SETTING Mainland Britain during 1994/5. SUBJECTS 1198 people (623 males, 575 females) aged 65 years or over, of whom 925 were living in private households and 273 were living in institutions. RESULTS Intermediate alcohol consumption (particularly 0.1-14 units week(-1); 1 unit = 8 g) derived from a 4-day diet diary or a 12-month recall questionnaire, was associated with higher intakes of vitamins C, E, B1, iron, calcium, energy from food, carbohydrate and non-starch polysaccharides than heavy alcohol consumption (28 + units week(-1)) or abstinence, after adjustment for a number of factors (age, sex, domicile, social class, cigarette smoking, self-reported health, grip strength and total energy intake). Intermediate alcohol consumption was also associated with higher blood concentrations (independent of intake) of vitamin C, beta-cryptoxanthin, lutein and calcium, with the lowest concentrations being found in heavy alcohol users. The lowest concentrations of serum ferritin were found in light drinkers and the highest levels in heavier alcohol drinkers. Alcohol consumption ranging from 0.1 to >28 units week(-1) was directly correlated with intakes of B vitamins, total energy and fat, with blood concentrations (independent of intake) of lycopene, high density lipoprotein (HDL)-cholesterol, plasma pyridoxal phosphate and retinol, and with blood pressure and grip strength. CONCLUSIONS Compared with abstinence and heavy drinking, light to moderate alcohol consumption in older people is associated with higher intakes of certain nutrients, and higher blood concentrations (independent of intake) of some micronutrient status indices, including antioxidants. The explanation for the latter associations remains unclear and further investigation is recommended. Heavier alcohol consumption is associated with both beneficial and adverse effects with respect to nutrient intakes and health status.

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Relationship between cigarette smoking and nutrient intakes and blood status indices of older people living in the UK: further analysis of data from the National Diet and Nutrition Survey of people aged 65 years and over, 1994/95

Objective To characterize relationships among blood pressure, pulse rate, vitamin C status and other protective and risk factors for older British people, from a national survey. Design A cross-sectional analysis of survey data. Setting A population study, representative of mainland Britain. Subjects Among 914 people of both sexes living in the community, 373 were taking blood-pressure-lowering drugs and were therefore excluded from the analyses. Interventions Completion of an interview on health, lifestyle and dietary habits, recording of a 4-day dietary record, anthropometry and taking of a blood sample to determine haematological and biochemical status. Main outcome measures Systolic and diastolic blood pressures, pulse rate, indices of micronutrient status including plasma ascorbate concentration, nutrient intake and haematology. Results Plasma ascorbate concentration was inversely correlated to systolic and diastolic blood pressures and pulse rate. Other covariates of blood pressure included age, sex, domicile, plasma retinol, fibrinogen and γ-tocopherol concentrations, erythrocyte count, prothrombin time and urine sodium: creatinine ratio. Covariates of pulse rate included sex, domicile, plasma fibrinogen and platelet count. Blood pressure was also correlated to intake of vitamin C. Conclusions Plasma ascorbate concentration and intake of vitamin C are covariates of blood pressure in older people living in Britain. New intervention studies are now needed, to test for possible causalities.

Does vitamin C reduce blood pressure?Results of a large study of people aged 65 or older

Objective To describe the extent of use of medicines by older people living in Britain, and to explore relationships with vitamin status indices. Design The National Diet and Nutrition Survey of people aged 65 years and over collected data from a British sample during 1994-95. The present study has made novel use of it, to relate medicine use with biochemical indices of vitamin status. Setting Eighty postcode areas, selected randomly from mainland Britain. Subjects 1506 people, 65 years and over gave information about use of medication, and a 4-day weighed food record. Three-quarters gave blood for status indices. Results 78% of those living in the community and 93% of those in institutions were using medication. Certain vitamin status indices: plasma retinol, erythrocyte folate and riboflavin, paradoxically suggested better status in users than in non-users of antihypertensive, gastrointestinal, central nervous system, corticosteroid or diabetic drugs. There was evidence of a link with renal insufficiency, especially for plasma retinol, but neither this nor increased nutrient intake, acute phase effects or haemoconcentration could explain the paradoxical associations. Conclusions Caution is needed in interpreting certain vitamin status indices, especially in older people who are extensively using medicines. New vitamin indices are needed, to avoid confounding interferences.

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Catherine M. Walmsley

Papers

Risk factors for poor iron status in British toddlers: further analysis of data from the National Diet and Nutrition Survey of children aged 1.5–4.5 years

Relationship between cigarette smoking and nutrient intakes and blood status indices of older people living in the UK: further analysis of data from the National Diet and Nutrition Survey of people aged 65 years and over, 1994/95

Does vitamin C reduce blood pressure?Results of a large study of people aged 65 or older

Use of medicines by older people in a large British national survey, and their relation to vitamin status indices.