Robert Patten

Nibbling versus Gorging: Metabolic Advantages of Increased Meal Frequency

We studied the effect of increasing the frequency of meals on serum lipid concentrations and carbohydrate tolerance in normal subjects. Seven men were assigned in random order to two metabolically identical diets. One diet consisted of 17 snacks per day (the nibbling diet), and the other of three meals per day (the three-meal diet); each diet was followed for two weeks. As compared with the three-meal diet, the nibbling diet reduced fasting serum concentrations of total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B by a mean (+/- SE) of 8.5 +/- 2.5 percent (P less than 0.02), 13.5 +/- 3.4 percent (P less than 0.01), and 15.1 +/- 5.7 percent (P less than 0.05), respectively. Although the mean blood glucose level and serum concentrations of free fatty acids, 3-hydroxybutyrate, and triglyceride were similar during both diets, during the nibbling diet the mean serum insulin level decreased by 27.9 +/- 6.3 percent (P less than 0.01) and the mean 24-hour urinary C-peptide output decreased by 20.2 +/- 5.6 percent (P less than 0.02). In addition, the mean 24-hour urinary cortisol excretion was lower by 17.3 +/- 5.9 percent (P less than 0.05) at the end of the nibbling diet than at the end of the three-meal diet. The blood glucose, serum insulin, and C-peptide responses to a standardized breakfast and the results of an intravenous glucose-tolerance test conducted at the end of each diet were similar. We conclude that in addition to the amount and type of food eaten, the frequency of meals may be an important determinant of fasting serum lipid levels, possibly in relation to changes in insulin secretion.

Effect of a Diet High in Vegetables, Fruit, and Nuts on Serum Lipids

We assessed the effect of a diet high in leafy and green vegetables, fruit, and nuts on serum lipid risk factors for cardiovascular disease. Ten healthy volunteers (seven men and three women aged 33 +/- 4 years [mean +/- SEM]; body mass index, 23 +/- 1 kg/m2) consumed their habitual diet (control diet, 29% +/- 2% fat calories) and a diet consisting largely of leafy and other low-calorie vegetables, fruit, and nuts (vegetable diet, 25% +/- 3% fat calories) for two 2-week periods in a randomized crossover design. After 2 weeks on the vegetable diet, lipid risk factors for cardiovascular disease were significantly reduced by comparison with the control diet (low-density lipoprotein [LDL] cholesterol, 33% +/- 4%, P < .001; ratio of total to high-density lipoprotein [HDL] cholesterol, 21% +/- 4%, P < .001; apolipoprotein [apo] B:A-I, 23% +/- 2%, P < .001; and lipoprotein (a) [Lp(a)], 24% +/- 9%, P = .031). The reduction in apo B was related to increased intakes of soluble fiber (r = .84, P = .003) and vegetable protein (r = -.65, P = .041). On the vegetable compared with the control diet, the reduction in total serum cholesterol was 34% to 49% greater than would be predicted by differences in dietary fat and cholesterol. A diet consisting largely of low-calorie vegetables and fruit and nuts markedly reduced lipid risk factors for cardiovascular disease. Several aspects of such diets, which may have been consumed early in human evolution, have implications for cardiovascular disease prevention.

Effect of nibbling versus gorging on cardiovascular risk factors: Serum uric acid and blood lipids

Nibbling has been reported to decrease serum cholesterol under fasting conditions, as well as the incidence of cardiovascular disease. It has been suggested that these effects are partly attributable to reduced concentrations of serum insulin, which are also observed. However, data on the effects of nibbling on serum lipids throughout the day are not available, nor is it known how nibbling affects serum uric acid as a further insulin-related risk factor for cardiovascular disease. We have attempted to address these issues. Seven healthy men consumed identical diets in a randomized crossover design either as three meals daily (control) or as 17 meals daily (nibbling) for 2 weeks. On day 13, serum lipid levels were measured over the course of the day (12 hours) together with the 24-hour urinary excretion of mevalonic acid as an indicator of hepatic cholesterol synthesis. Concentrations of uric acid in serum and 24-hour urinary excretion of uric acid were also determined. Mean (+/- SE) percent treatment differences in day-long total, low-density lipoprotein (LDL), and non-high-density lipoprotein (HDL) cholesterol, and apolipoprotein (apo) B were significant, with lower values on the nibbling diet as compared with the control diet (8.1% +/- 1.6%, P = .002; 12.2% +/- 2.6%, P = .005; 10.1% +/- 1.6%, P < .001; and 9.9% +/- 2.6%, P = .008, respectively). No significant difference was seen in the total to HDL cholesterol ratio or in urinary mevalonic acid excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Pathogenesis of acidosis in hereditary fructose intolerance

An 18-yr-old man with a classical history of hereditary fructose intolerance (HFI) developed typical biochemical changes following an oral fructose load: fructosemia, hypoglycemia, hypophosphatemia, hyperuricemia, and metabolic acidosis. Hypokalemia (3.1 meq/liter) was also noted. Three aspects of this case expand the published literature on this syndrome: (1) Metabolic acidosis was found to be due to both lactic acidosis and proximal renal tubular acidosis (RTA). We could quantitate the relative contribution of each, and found that urinary bicarbonate loss due to proximal RTA accounted for less than 10% of the fall in serum bicarbonate. The major cause of the metabolic acidosis was lactic acidosis. (2) Hypokalemia was found to be due to movement of potassium out of the extracellular space rather than to urinary loss. Potassium may have entered cells with phosphate or may have been sequestered in the gastrointestinal tract. (3) The coexistence of proximal RTA and acidemia made it possible to study the effect of acidemia on the urine-blood partial pressure of carbon dioxide (PCO2) gradient in alkaline urine (U-B PCO2). The U-B PCO2 measured during acidemia was much higher at the same urine bicarbonate concentration than in normal controls during alkalemia, providing evidence in humans that acidemia stimulates distal nephron hydrogen-ion secretion.