Jack L. Porter

Intestinal absorption of magnesium from food and supplements.

The purpose of this study was to measure magnesium absorption over the wide range of intakes to which the intestine may be exposed from food and/or magnesium-containing medications. Net magnesium absorption was measured in normal subjects after they ingested a standard meal supplemented with 0, 10, 20, 40, and 80 mEq of magnesium acetate. Although absorption increased with each increment in intake, fractional magnesium absorption fell progressively (from 65% at the lowest to 11% at the highest intake) so that absorption as a function of intake was curvilinear. This absorption-intake relationship was almost perfectly represented by an equation containing a hyperbolic function plus a linear function. Our results are statistically compatible with a magnesium absorption process that simultaneously uses a mechanism that reaches an absorptive maximum, plus a mechanism that endlessly absorbs a defined fraction (7%) of ingested magnesium. Compared to previous studies of calcium absorption, much less magnesium that calcium was absorbed at intakes above 8 mEq/meal, apparently due to greater restriction of intestinal permeability to magnesium. We also found that magnesium from a high magnesium-containing food source, almonds, was just as bioavailable as from soluble magnesium acetate. In contrast, magnesium absorption from commercially available enteric-coated magnesium chloride was much less than from magnesium acetate, suggesting that enteric coating can impair magnesium bioavailability.

The contribution of malabsorption to the reduction in net energy absorption after long-limb Roux-en-Y gastric bypass

BACKGROUND Roux-en-Y gastric bypass (RYGB) restricts food intake, and when the Roux limb is elongated to 150 cm, the procedure is believed to induce malabsorption. OBJECTIVE Our objective was to measure total reduction in intestinal absorption of combustible energy after RYGB and the extent to which this was due to restriction of food intake or malabsorption of ingested macronutrients. DESIGN Long-limb RYGB was performed in 9 severely obese patients. Dietary intake and intestinal absorption of fat, protein, carbohydrate, and combustible energy were measured before and at 2 intervals after bypass. By using coefficients of absorption to measure absorptive function, equations were developed to calculate the daily gram and kilocalorie quantities of ingested macronutrients that were not absorbed because of malabsorption or restricted food intake. RESULTS Coefficients of fat absorption were 92 ± 1.3% before bypass, 72 ± 5.5% 5 mo after bypass, and 68 ± 8.7% 14 mo after bypass. There were no statistically significant effects of RYGB on protein or carbohydrate absorption coefficients, although protein coefficients decreased substantially in some patients. Five months after bypass, malabsorption reduced absorption of combustible energy by 124 ± 57 kcal/d, whereas restriction of food intake reduced energy absorption by 2062 ± 271 kcal/d. Fourteen months after bypass, malabsorption reduced energy absorption by 172 ± 60 kcal/d compared with 1418 ± 171 kcal/d caused by restricted food intake. CONCLUSION On average, malabsorption accounted for ≈6% and 11% of the total reduction in combustible energy absorption at 5 and 14 mo, respectively, after this gastric bypass procedure.

Effect of D-glucose on intestinal permeability and its passive absorption in human small intestine in vivo

BACKGROUND Based on studies in animals, it has been proposed that carrier-mediated D-glucose absorption markedly enhances passive permeability of the jejunal mucosa, allowing the majority of D-glucose absorption to proceed passively. In this study, we evaluated this hypothesis in the human jejunum in vivo. METHODS Using the constant perfusion, nonabsorbable marker technique, permeability of jejunal mucosa was assessed by measuring the ratio of diffusion rates of urea/L-xylose and mannitol/L-xylose. Passive D-glucose absorption was quantitated using L-glucose and mannitol as probes for D-glucose. RESULTS Addition of D-glucose to perfused solutions did not change the diffusion ratios, indicating that D-glucose has no effect on the size of channels for passive diffusion across the jejunal mucosa. The fraction of total D-glucose absorption that could be attributed to a passive mechanism averaged 5%. In the human ileum in vivo, we detected no evidence of passive D-glucose absorption. CONCLUSIONS Carrier-mediated D-glucose absorption does not increase passive permeability of human jejunal mucosa to solutes with molecular radii between 2.6 and 4.0 A. The amount of D-glucose absorbed passively from the human jejunum is trivial compared with the overwhelmingly dominant mechanism, carrier-mediated transport. Our results do not support the concept that sodium-dependent nutrient transport increases tight junction permeability.

α1-antitrypsin excretion in stool in normal subjects and in patients with gastrointestinal disorders

Fecal clearance of plasma alpha 1-antitrypsin is used as a measure of protein leakage into the intestinal tract. In this study, the alpha 1-antitrypsin concentration in stool and the plasma clearance of alpha 1-antitrypsin in normal subjects and in a consecutive series of patients with chronic diarrhea, malabsorption, or unexplained hypoalbuminemia was determined. The normal subjects were studied in their usual state and also when they had diarrhea secondary to ingestion of lactulose, sorbitol, sodium sulfate, or phenolphthalein. The study first concluded that induced diarrhea can cause an increase in alpha 1-antitrypsin clearance; if this is not considered in establishing normal values, there may be an overdiagnosis of excess protein leakage in patients with diarrhea. Second, there is a highly significant statistical correlation (P less than 0.001) between alpha 1-antitrypsin clearance and serum albumin concentration. On average, the serum albumin falls below 3.0 g/dL (30 g/L) when the alpha 1-antitrypsin clearance exceeds 180 mL/day, a value that is about threefold higher than the upper limit of normal. Third, three of nine patients with microscopic/collagenous colitis had elevated clearance of alpha 1-antitrypsin; by contrast, abnormal alpha 1-antitrypsin clearance was not found in 23 patients with idiopathic secretory diarrhea. Fourth, fecal alpha 1-antitrypsin concentration is not a reliable index of abnormal alpha 1-antitrypsin clearance.

Carbohydrate malabsorption. Its measurement and its contribution to diarrhea.

The major purpose of this research was to gain insight into the effect of carbohydrate malabsorption on fecal water output. To do this we measured daily fecal output of total carbohydrate, reducing sugars, and organic acids (a product of bacterial fermentation). Normal subjects were studied in their native state and when diarrhea was induced by mechanisms that did and did not involve carbohydrate malabsorption. Patients with malabsorption syndrome were also studied. We concluded that: (a) Excretion of carbohydrate and its breakdown products can be expressed as a single number by converting organic acids to their monosaccharide equivalents. (b) Diarrhea per se causes only a trivial increase in fecal carbohydrate excretion. (c) The molar output of osmotic moieties in feces due to unabsorbed carbohydrate can be determined by adding fecal reducing sugars to organic acids and their obligated cations. This expression parallels almost exactly the effect of increasing doses of lactulose (a nonabsorbable sugar) on fecal water output; one excreted millimole obligates 3.5 g of stool water. This relationship can be used to predict the effect of carbohydrate malabsorption on stool water output in patients with diarrhea. (d) 12 of 19 patients with malabsorption syndrome due to various diseases had excessive fecal excretion of carbohydrate and its breakdown products; of the diseases that cause malabsorption syndrome, combined small and large bowel resection is most likely to result in excessive fecal excretion of carbohydrate and monosaccharide equivalents. In 6 of these 19 patients carbohydrate malabsorption appeared to be the major cause of diarrhea.

Effect of three laxatives and a cation exchange resin on fecal sodium and potassium excretion

BACKGROUND/AIMS The treatment of hyperkalemia in patients with renal insufficiency often includes the ingestion of sorbitol and a cation exchange resin. Sorbitol alone may be used to remove sodium and water from overloaded patients. The efficacy of these regimens has never been compared with other laxative or laxative-resin combinations. The aim of the study was to compare the relative effect of three laxatives with different mechanisms of action, alone and in combination with resin, on fecal sodium and potassium excretion. METHODS Sodium, potassium, and water excretion in 12-hour stool collections were analyzed after various laxative-resin combinations in normal subjects. RESULTS Correctol (yellow phenolphthalein) (Schering Plough Health Care Products, Memphis, TN) was more effective than sorbitol or sodium sulfate in causing fecal sodium and potassium loss. Resin recovery in stool was much greater with phenolphthalein than with other laxatives, and more potassium was excreted in stool with phenolphthalein-resin than with phenolphthalein alone or other laxative-resin combinations. Sorbitol caused more undesirable gastrointestinal symptoms than did sodium sulfate or phenolphthalein. CONCLUSIONS In normal people, phenolphthalein (1) is preferable to other laxatives in causing fecal sodium and potassium excretion, (2) hastens resin transit through the intestine compared with other laxatives, and (3) produces greater fecal potassium excretion when combined with resin than phenolphthalein alone or other laxative-resin combinations.

Effect of psyllium, calcium polycarbophil, and wheat bran on secretory diarrhea induced by phenolphthalein

BACKGROUND Fiber and water-holding agents are used for the treatment of constipation. In what may appear to be a paradox, they are sometimes also used for the treatment of diarrhea; it has been proposed that they sequester water from liquid stools and/or increase the ratio of fecal solids to fecal water and thereby improve stool consistency. The purpose of the present study was to test the validity of this hypothesis in normal subjects in whom secretory diarrhea was induced by phenolphthalein. METHODS In random sequence, 9 subjects with phenolphthalein-induced diarrhea were treated with placebo, psyllium, calcium polycarbophil, or wheat bran. RESULTS Calcium polycarbophil and wheat bran had no effect on fecal consistency or on fecal viscosity. By contrast, psyllium made stools firmer and increased fecal viscosity. In a dose-response study in 6 subjects, doses of 9, 18, and 30 g of psyllium per day caused a near linear increase in fecal viscosity. CONCLUSION Psyllium, but not calcium polycarbophil or wheat bran, improves fecal consistency and viscosity in subjects with experimentally-induced secretory diarrhea.

Active Intestinal Chloride Secretion in Human Carriers of Cystic Fibrosis Mutations: An Evaluation of the Hypothesis That Heterozygotes Have Subnormal Active Intestinal Chloride Secretion

To explain the very high frequency of cystic fibrosis (CF) mutations in most populations of European descent, it has been proposed that CF heterozygotes have a survival advantage when infected with Vibrio cholerae or Escherichia coli, the toxins of which induce diarrhea by stimulation of active intestinal chloride secretion. Two assumptions underlie this hypothesis: (1) chloride conductance by the CF transmembrane conductance regulator (CFTR) is the rate-limiting step for active intestinal chloride secretion at all levels of expression, from approximately zero in patients with CF to normal levels in people who are not carriers of a mutation; and (2) heterozygotes have smaller amounts of functional intestinal CFTR than do people who are not carriers, and heterozygotes therefore secrete less chloride when exposed to secretagogues. The authors used an intestinal perfusion technique to measure in vivo basal and prostaglandin-stimulated jejunal chloride secretion in normal subjects, CF heterozygotes, and patients with CF. Patients with CF had essentially no active chloride secretion in the basal state, and secretion was not stimulated by a prostaglandin analogue. However, CF heterozygotes secreted chloride at the same rate as did people without a CF mutation. If heterozygotes are assumed to have less-than-normal intestinal CFTR function, these results mean that CFTR expression is not rate limiting for active chloride secretion in heterozygotes. The results do not support the theory that the very high frequency of CF mutations is due to a survival advantage that is conferred on heterozygotes who contract diarrheal illnesses mediated by intestinal hypersecretion of chloride.

Effect of changing intestinal flow rate on a measurement of intestinal permeability

BACKGROUND/AIMS The flow rate of fluid through the proximal small intestine varies widely under normal physiological conditions. The aim of this study was to assess the effect of changes in flow rate on the passive permeability of the aqueous paracellular pathway of the human jejunum. METHODS Normal subjects were studied in vivo during constant perfusion of 30-cm loops of jejunum at flow rates of 5, 10, or 20 mL/min. The permeability ratio of L-xylose/urea was used to assess apparent permeability of the mucosa and to calculate the average pore radius of the aqueous pathway for passive diffusion. RESULTS Increasing jejunal flow rate from 5 to 20 mL/min significantly decreased the L-xylose/urea permeability ratio from 0.35 to 0.23 and decreased average calculated pore radius of the diffusion pathway from 13 A to 8 A. CONCLUSIONS Increases in flow rate in the normal physiological range decrease the estimated pore size of normal healthy jejunal mucosa. Because increasing flow rate is known to increase exposure of luminal fluid to the intervillus space, the results of this study are best explained by postulating that cells lining the sides of villi are less permeable than cells lining the villus tips.

Accurate enzymatic measurement of fecal bile acids in patients with malabsorption

Quantitation of fecal bile acid excretion can help elucidate the cause of diarrhea or steatorrhea. Fecal bile acids can be measured with gas chromatography-mass spectrometry, but this is time-consuming, expensive, and not available for clinical use. Relatively simple enzymatic methods have been described for the measurement of fecal 3alpha-hydroxy bile acids, but these have not been validated in patients with gastrointestinal disease. We found that an enzymatic method yielded falsely low results in patients with malabsorption syndromes for two reasons: First, the preliminary hydrolysis step did not completely deconjugate bile acids, precluding their extraction into diethyl ether for enzymatic assay. Second, long-chain fatty acids inhibited 3alpha-hydroxysteroid dehydrogenase activity. By increasing the duration of hydrolysis and the concentration of enzyme, we developed a simple, accurate, and reproducible method for measuring fecal 3alpha-hydroxy bile acids that agreed well with values obtained with the use of gas chromatography-mass spectrometry (R =.95), both in normal subjects and in patients with malabsorption syndromes.