MUST WATCH

AQR en vitamine C devraient être supérieurs à la quantité requise pour prévenir l’apparition de maladies. La vitamine C joue dans le corps des fonctions considérables qui augmentent son rôle dans l’état de santé du corps humain. Les fonctions biochimiques de la vitamine C sont notamment la stimulation de certains enzymes, la biosynthèse des collagènes, l’activation des hormones, des antioxydants, la détoxification de l’histamine, des fonctions des phagocytes, des leucocytes, la formation de la nitrosamine, et l’hydroxylation proline, entre autres. Ces fonctions ont trait aux effets sanitaires de la teneur en vitamine C dans un individu. En matière de santé humaine, la vitamine C a été associée à la réduction de l’incidence du cancer et de la tension artérielle, à l’immunité, au métabolisme des médicaments et à l’excrétion hydroxyproline urinaire, ainsi qu’à la régénération des tissus. Cette vitamine est nécessaire pour un bon métabolisme des médicaments dans le corps par un système d’oxydase de fonctions mixtes hépatiques adéquates. Des données épidémiologiques ont révélé le rôle préventif et curatif de la vitamine C sur certaines conditions de maladies dans le corps bien que des controverses persistent encore. La vitamine C est efficace dans la protection contre des lésions oxydatives dans les tissus; elle supprime également la formation de cancérigènes tels que les nitrosamines. Il existe un rapport inverse entre la tension artérielle et la vitamine C du plasma et la vitamine C. La vitamine C a un effet de réduction sur la tension artérielle, plus particulièrement sur la pression systolique que sur la pression diastolique. Les niveaux peu élevés de la vitamine C du plasma sont associés à la congestion cérébrale et à un risque élevé de toutes les causes de la mortalité. Une consommation élevée d’acide ascorbique augmente les niveaux ascorbiques du sérum et pourrait réduire les dangers de mort. Mots-clés: Vitamine C, cancer, tension artérielle, métabolisme des médicaments, immunité. INTRODUCTION Ascorbic acid, commonly known as vitamin C plays significant functions in the human body, though its function at the cellular level is not very clear. Vitamin C is needed for collagen synthesis, the protein that serves so many connective functions in the body. Among the body’s collagen-containing materials and structures are the framework of bone, gums and binding materials in skin muscle or scar tissue. Production of certain hormones and of neurotransmitters and the metabolism of some amino acids and vitamins require vitamin C. This vitamin also helps the liver in the detoxification of toxic substances in the system, and the blood in fighting infections. Ascorbic acid is important in the proper function of the immune system. As an antioxidant, it reacts with compounds like histamines and peroxides to reduce inflammatory symptoms. Its antioxidant property is associated with the reduction of cancer incidences [1, 2]. The requirement for vitamin C for adults does not seem to be uniform across cultures. This may be a pointer to the need for cultural-specific requirements for the nutrient. It African Journal of Food Agriculture and Nutritional Development (AJFAND): Volume 5 No 1 2005 3 has now been appreciated that ascorbic acid functions in cellular reactions and processes. Epidemiological data now point to reduction of colds with increased consumption of foods rich in vitamin C [3]. People are tempted to over-consume vitamin C because of its health benefits. Miniscule increases in blood vitamin C levels decrease the risk of death from all conditions [4]. This paper presents a review of epidemiological data on the role of ascorbic acid in certain human health conditions. Though there are many functions of vitamin C, its role in health is discussed in relation to cancer, blood pressure, immunity, drug metabolism and urinary hydroxyproline excretion. Vitamin C and Cancer Cancer is a global public health problem with increased mortality levels. Though there are many types of cancers, the review presents a general picture of the role of ascorbic acid in cancer. Vitamin C is effective in protecting against oxidative damage in tissues, and also suppresses formation of carcinogens like nitrosamines [4]. The WHO estimated an increase of over 10 million new cases of cancer. Despite progress against some rare forms of cancer, the overall death rate has increased [5]. Though Vitamin C is cytotoxic to tumor cells but non-toxic to normal cells, conventional medicine favors more powerful and toxic chemotherapeutic agents. Many studies have shown that vitamin C intake is inversely related to cancer, with protective effects shown for cancer of the lung, breast, pancreas, stomach, cervix, rectum and oral cavity [6]. The authors found that the oxidation of guanine, a purine in DNA was significantly reduced after vitamin C supplementation, but the oxidation of adenine also a purine was significantly elevated. The reduced level in the oxidation of guanine suggests that vitamin C acts as an antioxidant [5]. Extensive in vitro and in vivo vitamin C tests to determine its ability to prevent the adverse effects of, decrease the resistance to and increase the effects of chemotherapeutic have been conducted [7]. Combination of vitamin C and vitamin K given prior to chemotherapy increased survival and the effects of several chemotherapeutic agents in a murine ascitic living tumor model [8]. Vitamin C has also been shown to be safe to be used concurrently with radiation [9]. Administration of Vitamin A, β-carotene, E and C can reduce the incidence, and delay the progression of various cancers such as skin, those of the colon, stomach, esophagus, mammary glands and bladder [1, 4, 10, 11]. Epidemiological studies have revealed an inverse relationship between the intake of vitamins A, β-carotene, C and E, and the incidence of different cancers in humans. There is a decrease in cancer incidence and risk, in population with high content of these vitamins in the plasma. Carcinogenesis is related to cell differentiation, progression and metabolism, and collagen synthesis. The basic mechanism for carcinogenesis is cell differentiation, because cancer develops when there is loss of cell differentiation. Vitamins A, β-carotene, E and C have a profound influence on cell growth and differentiation. Vitamin C is a strong antioxidant that acts synergistically with Vitamin E as scavengers for free radicals in the body system, which are carcinogenic. Ascorbic acid, as sodium ascorbate exerts marked cytotoxic effects on several mammalian cells in culture. These effects are dose dependent. For example, Lupulescus [2] reported that vitamin C (upto 200 ug/ml) did not cause any morphological changes in mouse melanoma, mouse neuroblastoma, rat glioma African Journal of Food Agriculture and Nutritional Development (AJFAND): Volume 5 No 1 2005 4 and mouse fibroblasts in culture. At high concentrations (500-1000 ug/ml), vitamin C was lethal for neuroblastoma cells. Cytotoxic effects are also cell dependent, being stronger in human melanoma as compared to mouse melanoma cells. It has been suggested that vitamin C induced cytotoxicity is mediated primarily by hydrogen peroxide formation at cell surface, or thin cells. Cytotoxic activity can also be mediated by presence of cupric ions (Cu2+) in malignant melanoma cells that react with vitamin C and generate free radicals in solution. Vitamin C also reverses the chemically transformed cells to thin normal phenotype. Ultra structure and cell surface studies of cancer cells following vitamin C administration revealed observed cytolysis, cell membrane disruption, mitochondrial alterations, nuclear and nucleolar reduction, and increased phagolysosome formation in cancer cells following vitamin C administration [10]. Cell surface changes such as cytolysis, increased collagen synthesis, and cell membrane disorganization were predominant, and increased apoptotic and phagocytic activity were also seen. Quantitative estimation of cell organelles revealed that vitamin C affects the intracellular organelle distribution, playing an important role in cyto-differentiation of cell cancer [1, 10]. Hence, vitamins A, E and C markedly affect the cancer cells differentiation by exerting direct cytotoxic effects, modifying membrane biogenesis, light and gap junction formation, Golgi’s complex, autophagic and apoptotic activity, cell surface changes and sometimes reversing transformed cells to their normal cell type. This reversal is necessary in the reduction of possible cancer incidences. Changes of DNA, RNA and protein synthesis have been associated with cell differentiation and proliferation. The mechanism of action, however, is not fully understood. It has been suggested that most of the metabolic effects are mediated by transcription and translation processes at the genome level. Further, vitamins A, E and C modulate DNA synthesis and gene expression in a similar manner to that of steroid hormones. These vitamins may affect chemical mutagenicity and cellular status [2]. By affecting DNA, RNA and proteins at specific sites that are targets of electrophiles, the vitamins can control cell replication rate, leading to an altered cell rearranged codons and translocation of specific genes, or oncogenes. The vitamins A, E and C affect differently DNA, RNA and protein synthesis in cancer cells. Administration of vitamin C decreases DNA synthesis in the nuclei, RNA synthesis in the nucleoli, and proteins in cytoplasm of cancer cells. This inhibition of DNA, RNA and protein synthesis is accompanied by advanced ultra structural and cell surface changes, and will decrease progression of cancer. Vitamin C plays an important role in collagen synthesis. Collagen is an extracellular protein synthesized intracellularly as tropocollagen by the fibroblasts, and contains amino acids prolines, glycine and lysine. The major reaction in collagen synthesis is hydroxylation of proline to 4-hydroxyproline. This provides proper structural configuration and stability of collagen. The enzyme 4-hydroxylase, which is a tetramer, catalyzes hydroxylation of proline and its genes are differently located in human chromosomes. In some experiments ascorbic acid and its analogues specifically African Journal of Food Agriculture and Nutritional Development (AJFAND): Volume 5 No 1 2005 5 enhanced the collagen synthesis almost four-fold in cultured human skin fibroblasts, by increasing the incorporation of (3H-) proline into colagenase sensitive proteins. Lascorbate was found to be the most active compound, [2]. It is also possible that ascorbic acid can stimulate collagen synthesis by other mechanisms, independent of hydroxylation. Ascorbic acid induces lipid peroxidation and reactive aldehydes, a step required for collagen expression, collagen m-RNA levels, and collagen production in cultured human fibroblasts. Collagen gene expression is probably influenced by lipid perodixation, or through acetaldehyde formation, which consequently increases collagen gene transcription in cultured human fibroblasts. The mechanism by which vitamin C stimulates collagen gene expression is not very clear. Ascorbic acid can, therefore, stimulate collagen synthesis independent of proline hydroxylation by inducing lipid peroxidation. Ascorbic acid is thus the major vitamin regulating collagen synthesis, and provides stability to the procollagen single helix [1, 2] Blood Pressure Elevated blood pressure is a powerful determination of cerebro-vascular and coronary disease. Great efforts have been made towards the detection and treatment of hypertension since the 1960s. Some of the observed decrease in cardiovascular disease over the period has been attributed to better control of blood pressure among diagnosed hypertensives. The importance of nutrition in control of blood pressure is well documented. Obesity, dietary sodium and alcohol are associated with lower or higher blood pressure. Higher intake of polyunsaturated fatty acids and magnesium have also been linked with lower blood pressure [12]. Inverse associations with blood pressure and both plasma vitamin C and vitamin C have been reported. A study of the relationship between fasting vitamin C and cerebrovascular disease risk factors revealed reduction in hypertension in men. Men with serum vitamin C of 0.5 mg/dl had a mean systolic pressure of 122 mmHg compared with a mean of 113 mmHg for men with serum vitamin C of 0.9 mg/dl, a relative difference of -7%. The same men had a similar difference in diastolic pressure of 78 mmHg vs. 73 mmHg – 6% relative difference. Prevalence of hypertension was 7.5% in the low serum vitamin C group versus 1.0% among those with high levels of vitamin C [13]. An investigation to identify the association between BP plasma antioxidant vitamin revealed a significant trend for both systolic and diastolic pressure over qualities of plasma vitamin C with a – 5% difference in systolic pressure and a –4% difference in diastolic BP between highest and lowest quintiles of plasma vitamin C [14]. Similar significant negative trends between plasma vitamin C and both systolic and diastolic BP were observed in Chinese-American males and females aged 60-96 years who were not taking anti-hypertensive medication. The difference between mean systolic and diastolic BP levels in the highest and lowest quartiles were –21 mmHg (-14%) and – 8 mmHg (-9%), respectively [15]. Vitamin C appears to have a lowering effect on systolic pressure, more than it has on diastolic pressure. Other negative correlation between dietary vitamin C intake and both systolic and diastolic BP [16] and negative association between BP, and vitamin C intake and use of vitamin C supplements in African Journal of Food Agriculture and Nutritional Development (AJFAND): Volume 5 No 1 2005 6 Honolulu Heart Study [17] have also been reported. Diastolic pressure was not associated with vitamin intake. Individuals consuming vitamin C in adequate quantities are likely to have lower BP. It is a cheaper form of supplementation for developing communities. In a randomized placebo-controlled, cross-over trial on a mixed sample of 12 borderline hypertensives and 8 normotensives, there was reported a 4.4% drop in systolic BP between the placebo treatment and vitamin C treatment after four weeks of supplementation with 1 gram of vitamin C [18]. Vitamin C supplementation did not influence diastolic pressure. A cross-sectional study of the relationship of vitamin C intake and blood pressure in the elderly revealed relative differences in systolic and diastolic BP between subjects consuming 240 mg/day compared to those consuming 60 mg/day were –6.9% and –6.6%, respectively. The prevalence of elevated BP (systolic 160 mmHg or diastolic 100 mmHg) was approximately 50% lower across this range vitamin C intake (60, 60-119, 120-179, 180-239 240mg/day) [19]. Vitamin C thus appears to have a lowering effect on blood pressure of the elderly. A prospective population-based cohort study of 2419 randomly selected middle aged men (42-60yrs) with no history of stroke was conducted to examine whether plasma vitamin C modifies the association between overweight and hypertension and stroke [20]. Men who had the lowest levels of plasma vitamin C were at a higher risk of developing any stroke compared to men who had the highest levels of plasma vitamin C. Hypertensive men who had the lowest vitamin C levels were at an increased risk for any stroke and so were overweight men with low plasma vitamin C. Low plasma vitamin C was associated with increased stroke risk. An increase in the intake of vitamin C during the dietary fat reduction period could have accounted for a part of the blood pressure reduction [14, 15]. Decreased plasma ascorbic acid levels were associated with reduced plasma concentrations of 6-ketoprostaglandin-F, the metabolite prostacylin. Thus dietary antioxidants enhance production of prostacyclin by scavenging free radicals and peroxides, which inhibit prostacylin synthetase at concentrations above a certain threshold. Thus vitamin C and blood pressure appear to be related, in that adequate dietary vitamin C could exert a reducing effect on blood pressure, and especially if dietary fat intake is reduced.