Interaction of ethinyloestradiol with ascorbic acid in man.

Back, David; Breckenridge, AM; MacIver, M Bruce; Orme, ML; Purba, HS; Rowe, Philip H.

doi:10.1136/bmj.282.6275.1516

Cited by 57 publications

(16 citation statements)

References 2 publications

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“…Ascorbic acid treatment markedly diminished the increase of sulphate conjugated DA and NA in plasma after oral administration. This is consistent with ascorbic acid being a competitive inhibitor of sulphate conjugation (Houston et al, 1976;Back et al, 1981). The variable rise in free DA and lack of an associated rise in free NA in three of the four subjects studied may be explained by metabolism of these catecholamines by other pathways.…”

Section: Discussionsupporting

confidence: 80%

The effect of ascorbic acid on the sulphate conjugation of ingested noradrenaline and dopamine.

Dunne¹,

Davidson²,

Vandongen³

et al. 1984

Brit J Clinical Pharma

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Changes in the plasma concentration of free and conjugated noradrenaline (NA) and dopamine (DA) following oral administration of these catecholamines were examined in four normal males before and after treatment with ascorbic acid.The marked increase in plasma conijugated DA and NA was considerably reduced after ascorbic acid treatment, presumably due to competitive inhibition of sulphate conjugation. In one subject where there was a considerable delay in the appearance of sulphates, an early rise in free NA and DA concentration occurred. There were no changes in plasma free NA in the other subjects, although DA increased in two after ascorbic acid treatment.These findings emphasise the importance of sulphate conjugation in the gut or liver in inactivating endogenous amines in foods and indicate that interference of this protective mechanism may arise from high doses of ascorbic acid and other related compounds which compete for sulphation.

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Section: Discussionsupporting

confidence: 80%

The effect of ascorbic acid on the sulphate conjugation of ingested noradrenaline and dopamine.

Dunne¹,

Davidson²,

Vandongen³

et al. 1984

Brit J Clinical Pharma

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“…Our hypothesis was that several nutrients that may result in increased 2‐hydroxylated oestrogen metabolites (low energy intake, high protein intake, low carbohydrate intake, high cruciferous vegetable intake and high fibre intake) would be associated with reduced risk of hypospadias among offspring 10–14 . In contrast, high vitamin C intake was hypothesised to result in increased oestrogen levels; vitamin C competes with oestrogens for sulphate conjugation during first‐pass metabolism, thus resulting in reduced clearance of oestrogen via the hepatic drug‐oxidising system 27–29 . Our results did not support these hypotheses, with the exception of our finding that protein intake in the highest vs. lowest quartile was associated with lower risk (OR 0.6 [95% CI 0.5, 0.9]).…”

Section: Commentsmentioning

confidence: 63%

Nutritional Factors and Hypospadias Risks

Carmichael

Feldkamp

et al. 2012

Paediatric Perinatal Epid

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SUMMARY We examined whether hypospadias was associated with several aspects of the diet, including intake of animal products, intake of several nutrients and food groups related to a vegetarian diet and estrogen metabolism, and diet quality. The study included deliveries from 1997 to 2005 that were part of the National Birth Defects Prevention Study. Diet was assessed by food frequency questionnaire during maternal telephone interviews, and two diet quality indices were developed based on existing indices. Analyses included 1,250 cases with second or third degree hypospadias (urethra opened at the penile shaft, scrotum or perineum) and 3,118 male, liveborn, non-malformed controls. All odds ratios (ORs) and 95% confidence intervals (CI) were estimated from logistic regression models that included several potential confounders, including energy intake. Intake of animal products was not associated with hypospadias; e.g., the adjusted OR for any versus no intake of meat was 1.0 (95% CI 0.6, 1.6). Frequency of intake of meat or other animal products was also not associated with hypospadias, nor was intake of iron or several nutrients that are potentially related to estrogen metabolism. Diet quality was also not associated with hypospadias; the ORs for diet quality in the highest versus lowest quartile for the two diet quality indices were 1.0 (95% CI 0.6, 1.6) and 0.9 (95% CI 0.7, 1.1). In conclusion, this large study does not support an association of a vegetarian diet or worse diet quality with hypospadias.

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“…[129,130] Vitamin C (ascorbic acid) is inactivated by sulphate conjugation in the small intestinal mucosa)131] Ethinylestradiol shares this metabolic pathway. [l32-134] Since sulphate conjugation is a capacity-limited process, pharmacological doses (lOOOmg) of vitamin C can result in competitive inhibition of sulphate conjugation of ethinylestradiol and thereby increase the systemic availability of the steroid by up to 60%.0 32 , 133,135] When pharmacological doses of vitamin Care ingested for I month by users of oral contraceptives , drug action on certain clotting factors appears to be enhanced. This was attributed to the conversion of a low-dose contraceptive pill into a high-dose pill by inhibiting steroid inactivation.l' P" Sulphate conjugation ofother drug s was found also to be inhibited by the application of vitamin C 1 to 2g for several days .ll37 l Furthermore, pharmacological doses of vitamin C can impair hepatic phenazone biotransformation.UP' Similar effects have also been described for other drugsJ1 31 l Enriched vitamin K in certain plant food has been reported to cause resistance to warfarinJ139-141] Yet the nutritional histories given in these reports provide evidence that the plant foods were also rich in certain indoles known to stimulate drug metabolism (see section 5.1) .…”

Section: 3 Vitaminsmentioning

confidence: 99%

Influence of Diet and Nutritional Status on Drug Metabolism

Walter‐Sack

Klotz

1996

Clinical Pharmacokinetics

180

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Genetic and environmental factors contribute to a wide inter- and intraindividual variability in drug metabolism. Among the environmental factors that may influence drug metabolism, the diet and nutritional status of the individuals are important determinants. As altered drug-metabolising enzyme activities can influence the intensity and duration of drug action, such factors should be considered in pharmacotherapy. For this reason the effects of dietary energy, protein deficiency, nutritional ingredients, special diet forms and nutrition regimens and malnutritional states must be differentiated. In various pharmacokinetic studies different model drugs metabolised either by oxidative phase I pathways [e.g. phenazone (antipyrine), aminopyrine, phenacetin, theophylline, propranolol, nifedipine] or phase II conjugation reactions [e.g. paracetamol (acetaminophen), oxazepam] were used and from the calculated pharmacokinetic data some information on the involved and affected drug-metabolising enzymes [e.g. cytochrome P450 (CYP) subspecies, glucuronosyltransferases] can be generated. It is well known that smoking, charcoal broiled food or cruciferous vegetables induce the metabolism of many xenobiotics, whereas grapefruit juice increases the oral bioavailability of the high clearance drugs nifedipine, nitrendipine or felodipine by inhibiting their presystemic (intestinal) elimination. Energy deficiency, and especially a low intake of protein, will cause a decrease of about 20 to 40% in phenazone and theophylline clearance and elimination of those drugs can be accelerated by a protein-rich diet. In the same way, protein deficiency induced by either vegetarian food or undernourishment will have the opposite pharmacokinetic consequences. On the basis of some more examples from the literature it is emphasised that the variable influence of the above factors should be taken into account in study participant selection and study design when the pharmacokinetics of a drug must be determined in healthy individuals and/or patients.

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Interaction of ethinyloestradiol with ascorbic acid in man.

Cited by 57 publications

References 2 publications

The effect of ascorbic acid on the sulphate conjugation of ingested noradrenaline and dopamine.

The effect of ascorbic acid on the sulphate conjugation of ingested noradrenaline and dopamine.

Nutritional Factors and Hypospadias Risks

Influence of Diet and Nutritional Status on Drug Metabolism

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