Selective COX-2 inhibition affects fatty acids, but not COX mRNA expression in patients with FAP

Familial adenomatous polyposis (FAP) provides a model for sporadic colorectal cancer development. Cyclooxygenase (COX) inhibition may ameliorate polyp development, but rofecoxib was withdrawn due to cardiovascular side effects. Although this selective COX-2 inhibitor, like diet, may alter the fatty acid and eicosanoid pattern, data on the potential alteration in tissues after use, are scarce. The aims were to study if rofecoxib might influence the fatty acid distribution in serum phospholipids and duodenal lesions, mRNA for COX-1 and COX-2 in leucocytes and duodenal lesions, and finally plasma levels of PGE2 in a randomized, double-blind, placebo controlled study (n = 38). Significant reductions were found for essential fatty acid index both in serum phospholipids (P = 0.01, 95% CI = −0.9; −0.1), and in duodenal lesions (P = 0.04, 95 CI % = −0.9; −0.1) after treatment. No treatment effects were found on the COX mRNA expression, or in the plasma PGE2 levels. Dietary AA/EPA ratio was inversely associated with all the indicators of EFA status (all P < 0.01). These findings suggest that the effects of COX chemoprevention should be further investigated in FAP and that dietary needs should be included in the treatment of FAP

Plant based dietary supplement increases urinary pH

<p>Abstract</p> <p>Background</p> <p>Research has demonstrated that the net acid load of the typical Western diet has the potential to influence many aspects of human health, including osteoporosis risk/progression; obesity; cardiovascular disease risk/progression; and overall well-being. As urinary pH provides a reliable surrogate measure for dietary acid load, this study examined whether a plant-based dietary supplement, one marketed to increase alkalinity, impacts urinary pH as advertised.</p> <p>Methods</p> <p>Using pH test strips, the urinary pH of 34 healthy men and women (33.9 +/- 1.57 y, 79.3 +/- 3.1 kg) was measured for seven days to establish a baseline urinary pH without supplementation. After this initial baseline period, urinary pH was measured for an additional 14 days while participants ingested the plant-based nutritional supplement. At the end of the investigation, pH values at baseline and during the treatment period were compared to determine the efficacy of the supplement.</p> <p>Results</p> <p>Mean urinary pH statistically increased (p = 0.03) with the plant-based dietary supplement. Mean urinary pH was 6.07 +/- 0.04 during the baseline period and increased to 6.21 +/- 0.03 during the first week of treatment and to 6.27 +/- 0.06 during the second week of treatment.</p> <p>Conclusion</p> <p>Supplementation with a plant-based dietary product for at least seven days increases urinary pH, potentially increasing the alkalinity of the body.</p

Intestinal absorption of essential fatty acids under physiological and essential fatty acid-deficient conditions

The adequate supply of essential fatty acids (EFA) to the body depends upon sufficient dietary intake and subsequent efficient intestinal absorption. Lipid malabsorption is not only a leading cause of EFA deficiency (EFAD), but also occurs secondarily to EFAD. Understanding the relationship between EFAD and lipid malabsorption may be helpful in the development and optimization of oral treatment strategies. Sequential steps involved in EFA absorption, including lipolpsis, solubilization by bile, uptake into the enterocyte, and chylomicron secretion into lymph are reviewed, both under physiological and EFAD conditions. EFAD in itself affects the deficiency state by impairment of EFA absorption due to its effects on bile formation and on chylomicron secretion. These processes may be interrelated as decreased phosphatidylcholine secretion into the bile (a consequence of EFAD) is known to result in decreased chylomicron assembly and secretion. Possible treatments of EFAD include increasing dietary amounts of triacylglycerols and/or specifically tailoring lipids (structured triacylglycerols, EFA-rich phosphatidylcholines, EFA-ethyl esters). It is forseen that insights into the relationship between lipid malabsorption and EFAD will refine rational approaches to prevent and treat EFAD in specific patient groups

The metabolic importance of unabsorbed dietary lipids in the colon

Digestion and absorption of lipids is a highly efficient process. From Western diets about 95% will be absorbed. This implies that together with lipids from endogenous sources 6-8 g of lipids will enter the colon daily. This input significantly increases during various lipid malabsorption syndromes. It has long been assumed that the biological fate of unabsorbed lipids is physiologically not relevant. However, significant microbial lipid metabolism occurs. Circumstantial evidence is arising which supports a role of unabsorbed lipid metabolites in the development of colonic diseases. Lipid metabolites may act as detergents in the colon, leading to mucosal injury and reactive hyperproliferation, which in its turn could promote tumour development. Lipid metabolites could also be transformed in biological active metabolites, which have a tumour promoting potency. More mechanistic information is needed on the colonic metabolic fate of lipids in order to develop strategies for manipulating colonic flora in the prevention of lipid related colonic diseases

Intestinal absorption and postabsorptive metabolism of linoleic acid in rats with short-term bile duct ligation

We investigated in bile duct-ligated (BDL) and sham-operated control rats whether the frequent presence of essential fatty acid deficiency in cholestatic liver disease could be related to linoleic acid malabsorption, altered linoleic acid metabolism, or both. In plasma of BDL rats, the triene-to-tetraene ratio, a biochemical marker for essential fatty acid deficiency, was increased compared with controls (0.024 +/- 0.004 vs. 0.013 +/- 0.001; P <0.05). Net and percentage of dietary linoleic acid absorbed were decreased in BDL rats compared with control rats (1.50 +/- 0.16 mmol/day and 81.3 +/- 3.3% vs. 2.08 +/- 0.07 mmol/day and 99.2 +/- 0.1%, respectively; each P <0.001). At 24 h after [C-13] linoleic acid administration, BDL rats had a similar ratio of plasma [C-13] arachidonic acid to plasma [ 13C] linoleic acid concentration compared with control rats. Delta (6)-Desaturase activity was not significantly different in hepatic microsomes from control or BDL rats. At 3 h after [C-13] linoleic acid administration, plasma appearance of [C-13] linoleic acid and cumulative expiration of (CO2)-C-13 were decreased in BDL rats, compared with controls (by 54% and 80%, respectively). The present data indicate that the impaired linoleic acid status in cholestatic liver disease is mainly due to decreased net absorption and not to quantitative alterations in postabsorptive metabolism