For many dietary changes satisfactory prediction of the average change in the serum cholesterol level of man in mg./100 ml., is given by Δ Chol. = 1.35(2ΔS − ΔP) + 1.5ΔZ where S and P are percentages of total calories provided by glycerides of saturated and polyunsaturated fatty acids in the diet and Z2 = mg. of dietary cholesterol/1000 Cal. This formula fails, however, when the dietary change involves large amounts of cocoa butter and discrepancies also appear with beef tallow or hydrogenated coconut oil diets. Controlled dietary experiments at the University of Minnesota and at 2 other centers, provide 63 sets of comparisons of serum cholesterol averages for groups of men on each of 2 chemically characterized diets. Least-squares analysis indicates that stearic acid, as well as saturated fatty acids containing fewer than 12 carbon atoms, have little or no effect on serum cholesterol in man. The equation, Δ Chol. = 1.2(2ΔS′ − ΔP) + 1.5ΔZ, yields good correlation (r = 0.93) with the observed values in these 63 sets of data. This formulation also resolves heretofore puzzling discrepancies in the literature.

Serum cholesterol response to changes in the diet: IV. Particular saturated fatty acids in the diet.

Data from 227 men in 10 sets of controlled dietary experiments in 5 institutions gave the least-squares solution: [see text] with S.E. of slope --±0.44, where X is the serum cholesterol level of an individual, X is the average for all men on the same diet, and Δ is the response to a given dietary change. Equations, a chart and a table are provided for the prediction of the serum cholesterol response when change is made from one diet to another when cholesterol and fatty acid compositions of the diets are known. Comparison of predicted with observed average values in recently published data on samples of free-living people changing diets on prescription designed to lower serum cholesterol gave, predicted versus observed Δ: −30.0 vs. −28.5 and −27.2 vs. -30.1 mg./l00 ml. in men and women in caloric balance. In a sample of men who were also losing weight on a low-fat, low-cholesterol diet a change of −33.5 was predicted versus −39.8 observed.

Serum cholesterol response to changes in the diet: III. Differences among individuals.

Studies were undertaken to define the mechanism whereby bile acid facilitates fatty acid and cholesterol uptake into the intestinal mucosal cell. Initial studies showed that the rate of uptake (Jd) of several fatty acids and cholesterol was a linear function of the concentration of these molecules in the bulk phase if the concentration of bile acid was kept constant. In contrast, Jd decreased markedly when the concentration of bile acid was increased relative to that of the probe molecule but remained essentially constant when the concentration of both the bile acid and probe molecule was increased in parallel. In other studies Jd for lauric acid measured from solutions containing either 0 or 20 mM taurodeoxycholate and saturated with the fatty acid equaled 79.8+/-5.2 and 120.8+/-9.4 nmol.min(-1).100 mg(-1), respectively: after correction for unstirred layer resistance, however, the former value equaled 113.5+/-7.1 nmol.min(-1).100 mg(-1). Maximum values of Jd for the saturated fatty acids with 12, 16, and 18 carbons equaled 120.8+/-9.4, 24.1+/-3.2, and 13.6+/-1.1 nmol.min(-1).100 mg(-1), respectively. These values essentially equaled those derived by multiplying the maximum solubility times the passive permeability coefficients appropriate for each of these compounds. The theoretical equations were then derived that define the expected behavior of Jd for the various lipids under these different experimental circumstances where the mechanism of absorption was assumed to occur either by uptake of the whole micelle, during interaction of the micelle with an infinite number of sites on the microvillus membrane or through a monomer phase of lipid molecules in equilibrium with the micelle. The experimental results were consistent both qualitatively and quantitatively with the third model indicating that the principle role of the micelle in facilitating lipid absorption is to overcome unstirred layer resistance while the actual process of fatty acid and cholesterol absorption occurs through a monomer phase in equilibrium with the micelle.

/pdf/the-mechanism-whereby-bile-acid-micelles-increase-the-rate-46jv10l5mk.pdf

The mechanism whereby bile acid micelles increase the rate of fatty acid and cholesterol uptake into the intestinal mucosal cell.

Specificities of lipases.

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1016/0014-5793%2871%2980109-6

Enzyme entrapment in liposomes.

In studies in animals it has been shown (1) that the chain length of a fatty acid is related to the extent of its absorption; i.e., the greater the molecular weight, the less the degree of absorption. It has been our purpose to find whether this relationship is true also in patients with steator-rhea. We have studied the absorption of various fatty acids, fed as triglycerides, in patients who have disturbed fat absorption due to celiac disease, cystic fibrosis of the pancreas, and ileectomy. The steatorrhea in each of these categories is based on distinctly different defects. In celiac disease the poor fat absorption is caused by. dysfunction of the mucosal cells (2), but in cystic fibrosis the steator-rhea reflects diminished lipolysis due to deficiency of pancreatic lipase. In the third instance-operative shortening of the intestine-there is obviously a reduction of mucosal surface available for absorption. Also it has been our purpose to determine whether the absorption of a given fatty acid is influenced by simultaneously feeding other fatty acids. This may have therapeutic implications in that it could afford a guide to the choice of dietary fats for patients with steatorrhea. Various experimental designs have been used in the past for studying the process of fat absorption. Some investigations, in both animal experi-TABLE I Composition offat mixtures used in the different experiments Fatty acids* (%)t Fat and fat mixtures

/pdf/differences-in-absorption-of-the-various-fatty-acids-studied-4cii9jug0h.pdf

Differences in absorption of the various fatty acids studied in children with steatorrhea

The quintessence of Verzar's theory is: complete hydrolysis of fat in the intestine and synthesis of the fatty acids to triglycerides in the intestinal cells, via an intermediate stage of phospholipids. The main features of Frazer's theory are: hydrolysis of part of the fat into mono- and diglycerides and free fatty acids in the intestine,

/pdf/the-absorption-of-fats-studied-in-a-child-with-chylothorax-1gaknievys.pdf

The absorption of fats studied in a child with chylothorax.

The majority of patients with glycogenosis of the liver have one of three types of enzyme deficiency: deficiencyofglucose-6-phosphatase, ofthe debranching enzyme system, or of the phosphorylase system (Illingworth, 1961; Hers and Van Hoof, 1968). The severity of the disease and of its manifestations, such as hypoglycaemia and acidosis, is related to the underlying enzyme defect (van Creveld and Huijing, 1965). Treatment of patients with liver glycogenosis is dietary. The diet aims at reducing the effects of the metabolic disturbance and must vary with the type of enzyme defect (Fernandes and van de Kamer, 1965, 1968). It is important to start dietary management as early as possible, and therefore to diagnose the disease and the enzyme deficiency involved, at an early age. The definitive diagnostic procedure is assay of the enzymes, either in liver tissue orfor debranching enzyme and phosphorylase-in the leucocytes. But it would be useful to have available simpler tests to screen children in whom liver glycogen disease is suspected. Various screening procedures have been recommended, such as the epinephrine tolerance test (Howell, Ashton, and Wyngaarden, 1962), glucagon tolerance test (Hug, 1962; Lowe et al., 1962), and intravenous tolerance test with fructose (Hers, 1959) or galactose (Schwartz, Ashmore, and Renold, 1957). Ockerman (1967) has reviewed the application of these tests. In our experience, they often have drawbacks. With the glucagon test, all our patients with deficiency of the phosphorylase system showed a rise in blood glucose no different from that of normal children. Thus, the statement of Sokal, Lowe, and Sarcione (1962) that a rapid rise of 50 mg./100 ml. or more in blood glucose after intramuscular glucagon virtually rules out liver glycogen disease, does not hold for this group of patients. Moreover, the glucagon test is usually performed after prolonged fasting

https://adc.bmj.com/content/archdischild/44/235/311.full.pdf

A screening method for liver glycogen diseases.

Type IV glycogen storage disease is caused by a deficiency of the branching enzyme, oc-1,4-glucan: ox-1,4-glucan 6-glucosyltransferase, EC 2.4.1.18 (Brown and Brown, 1966); and is characterized by the accumulation in liver, spleen, and other organs of glycogen with an abnormal structure. This glycogen has long outer chains, relatively few branch points, and gives a blue colour with iodine. It thus resembles amylopectin, and the disease is sometimes called amylopectinosis. The disease is rare, and only 4 patients have been described (Andersen, 1956; Sidbury et al., 1962; Brown and Brown, 1966; Holleman, van der Haar, and de Vaan, 1966). We present a fifth patient, a sib of the patient described by Holleman et al. (1966). The diagnosis was made during life, by the assay of the branching enzyme activity in leucocytes. An attempt was made to treat the child with oc-glucosidase, and with zinc-glucagon, both administered parenterally.

https://adc.bmj.com/content/archdischild/43/229/347.full.pdf

Branching enzyme-deficiency glycogenosis: studies in therapy.

Galactose and fructose, administered orally to five children with liver glycogenosis due to deficiency of the debranching enzyme system, were found to be rapidly converted into glucose. A fluctuating glucose curve and a significant rise of blood lactate were observed during oral hexose challenge. Some proteins and amino acid mixtures, administered orally, induced a small and prolonged rise of blood glucose.

J. Fernandes

Papers

Differences in absorption of the various fatty acids studied in children with steatorrhea

The absorption of fats studied in a child with chylothorax.

A screening method for liver glycogen diseases.

Branching enzyme-deficiency glycogenosis: studies in therapy.

Hexose and protein tolerance tests in children with liver glycogenosis caused by a deficiency of the debranching enzyme system.