Interaction with dietary constituents

Figure 6.1 Schematic representation of the role played by the gut microflora in maintaining host health through interactions with cells of the mucosa, immunological interactions, interactions between microorganisms and interactions with dietary constituents.

The expression of a significant gut wall first-pass extraction ratio has several implications for affected drugs. First, oral bioavailability is lower than would be expected from the extent of absorption and the hepatic first-pass extraction. Second, the variability in expression of gut wall metabolic enzymes and transporters can lead to significant variability in gut wall first-pass extraction and thus oral bioavailability. Finally, the site of expression of these enzymes and transporters (i.e., the villus tip) brings them into contact with potentially co-administered drugs or dietary constituents, which could be inhibitors or inducers. Thus, there is the potential for drug-drug interactions at the level of the gut wall. 

We have already met several of the important concepts in this topic, so now it is time to round them up and bring out the major principles. In the first place drug molecules clearly might interact with food molecules in the lumen of the gut. Perhaps the best-known example of this is the interaction between the tetracyclines and dietary calcium and iron. The binding, which occurs between them, produces a chelate, which is not particularly lipid-soluble, and therefore the overall absorption of tetracycline may be reduced to the point where plasma levels do not achieve effective antibiotic concentrations. The commonest dietary constituent to produce this binding is milk with its high calcium content. Tetracycline ingestion should be separated from food as far as possible. 

The full extent to which saponins reduce cholesterol absorption requires further study. Because of the large number of saponins present in the food supply, it is possible that all of the mechanisms discussed earlier contribute to reduced cholesterol absorption. Unlike plant sterols in which their mode of action is relatively well defined, there are probably multiple effects of saponins within the intestinal tract, including their ability to interact with other dietary constituents and the ability of some saponins to be absorbed systemically. The regulatory effects of saponins on cellular cholesterol transport have not been examined. 

Microminerals. Manganese probably interacts to some extent with many trace elements depending on the concentration of Mn and on the concentration of the other interactive element. Other dietary constituents probably play a role as well. The discussion here, however, will be limited to the interaction of Mn with Co and Fe. Thomson and Valberg (30) perfused test solutions of Fe, Co and Mn into open-ended duodenal loops of rats and reported that Mn uptake was inhibited by both Co and Fe, and... 

However, a range of foreign proteins, which are potential antigens, are present in the diet and are absorbed from the gastrointestinal tract. The immune systems of most individuals become tolerant via a regulatory system which prevents adverse reactions to food constituents and additives. However some individuals seem predisposed to allergic diseases and do not become tolerant and so may develop adverse reactions to dietary constituents. It is possible that the interaction of a breakdown product of tartrazine with a protein in the body could be sufficient to cause an allergic reaction in some sensitive individuals. 

Determination of human requirements for dietary trace minerals necessarily includes knowledge of the factors which affect the availability of minerals for absorption Interactions of dietary minerals with organic constituents of the diet and with other minerals are complex Careful study of mineral absorption in human subjects is required to delineate dietary requirements and the factors which affect them ... 

Vitamin B complex is the collective term for a number of water-soluble vitamins found particularly in dairy products, cereals and liver.Vitamin B (thiamine) is used by mouth for dietary supplement purposes and by injection in emergency treatment of Wernicke-Korsakoff syndrome. Vitamin B2 (riboflavin) is a constituent of the coenzyme FAD (flavine adenine dinucleotide) and FMN (flavine mononucleotide) and is therefore important in cellular respiration. Vitamin Be (pyridoxine) is a coenzyme for decarboxylases and transamination, and is concerned with many metabolic processes. Overdose causes peripheral neuropathy. It may be used medically for vomiting and radiation sickness and for premenstrual tension. Pyridoxine has a negative interaction with the therapeutic use of levodopa in parkinsonism by enhancing levodopa decarboxylation to dopamine in the periphery, which does not then reach the brain. The antitubercular drug isoniazid interferes with pyridoxine, and causes a deficiency leading to peripheral neuritis that may need to be corrected with dietary supplements. Vitamin B ... 

Many of the interactions of herbal medicines (health foods, dietary supplements) with warfarin in the published Uterature are solely hypothetical based on the postulated pharmacological effects of known chemical constituents of the plants. These mechanisms are discussed further below. Where specific clinical data on a herbal medicine interaction with warfarin are available, this is covered in a separate monograph. 

As with any dietary constituent, the evidence on the influence of palmitic acid on health is variable. Rather than identifying the influence of palmitic acid on health as effects , it may be more appropriate to associate the mechanisms, actions, and interactions of palmitic acid as potential implications . As palmitic acid is one of the most abimdant fatty acids, fimctioning as potent uncoupling agents of cell communication it is not surprising that it occupies a substantial role in metabolism, health and disease (Kremmyda et al., 2011 Tvrzicka et al., 2011). Palmitic acid has been identified as a potential dietary agent for increased cardiovascular disease (CVD) risk (Siri-Tarino et al., 2010). 

On the other hand, if we assume that the reported changes in body composition are accurate for each nial, it appears that the effect of CLA supplementation in adults was not related to body size, adiposity, or dose. The composition of the concurrent dietary intake might be one factor contributing to the variabihty in body composition outcome. Studies conducted in mice demonstrated that the quantity and type of dietary fat did not affect the CLA response in that species (11). However, the type of protein in the diet altered the fat-reducing capability of CLA in rats (36). In the clinical trials, with the exception of the San Erancisco study (32), dietary intake was not controlled, raising the possibility that CLA could be interacting with other dietary constituents that might attenuate or accentuate its effect. 

Studies on starvation, however, are compatible with a major effect of changing the proportion of the macromolecular constituents of isocaloric diets. This reconciliation of seemingly contradictory results offers an opportunity to stress the complex effects of several dietary factors and the possibility for interactions among them. 

The behavior of minerals is often influenced by the presence of other food constituents. The recent interest in the beneficial effect of dietary fiber has led to studies of the role fiber plays in the absorption of minerals. It has been shown (Toma and Curtis 1986) that mineral absorption is decreased by fiber. A study of the behavior of iron, zinc, and calcium showed that interactions occur with phytate, which is present in fiber. Phytates can form insoluble complexes with iron and zinc and may interfere with the... 

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