Positive Psychological Intervention Effects on Depression: Positive Emotion Does Not Mediate Intervention Impact in a Sample with Elevated Depressive Symptoms.

Positive psychological interventions (PPIs), programs that specifically target positive emotions, cognitions, and behaviors, have been shown to reduce depression and improve other aspects of psychological well-being. However, potential pathways linking PPIs to better outcomes have been under-explored. In this paper, we report the results of a randomized trial of a self-guided online delivered PPI called MARIGOLD (Mobile Affect Regulation Intervention with the Goal of Lowering Depression). Participants with elevated depression were randomized to receive MARIGOLD (n = 539) or an emotion reporting control condition (n = 63). In addition to testing direct effects of the intervention on depressive symptoms, we explored whether positive or negative emotion-operationalized as past day, past week, reactivity, or flexibility-mediated the intervention impact on depression. Results demonstrated that participants in the MARIGOLD condition had reduced depressive symptoms compared to controls and, although the effect did not reach statistical significance, reductions in past day negative emotion appeared to mediate this effect. Contrary to hypotheses, the intervention did not increase positive emotion compared to the control condition. Discussion focuses on the need for future studies to continue investigating the mechanisms of action for PPIs with emphasis on theoretically-based measurement and operationalization of emotion and other potential mediators to maximize the ultimate impact of PPIs on psychological well-being. Clinical Trials registration #NCT02861755.

Failure of hyperglycemia and hyperinsulinemia to compensate for impaired metabolic response to an oral glucose load.

OBJECTIVE: To evaluate whether the augmented insulin and glucose response to a glucose challenge is sufficient to compensate for defects in glucose utilization in obesity and type 2 diabetes, using a breath test measurement of integrated glucose metabolism. METHODS: Non-obese, obese normoglycemic and obese type 2 diabetic subjects were studied on 2 consecutive days. A 75g oral glucose load spiked with ¹³C-glucose was administered, measuring exhaled breath ¹³CO2 as an integrated measure of glucose metabolism and oxidation. A hyperinsulinemic euglycemic clamp was performed, measuring whole body glucose disposal rate. Body composition was measured by DEXA. Multivariable analyses were performed to evaluate the determinants of the breath ¹³CO2. RESULTS: Breath ¹³CO2 was reduced in obese and type 2 diabetic subjects despite hyperglycemia and hyperinsulinemia. The primary determinants of breath response were lean mass, fat mass, fasting FFA concentrations, and OGTT glucose excursion. Multiple approaches to analysis showed that hyperglycemia and hyperinsulinemia were not sufficient to compensate for the defect in glucose metabolism in obesity and diabetes. CONCLUSIONS: Augmented insulin and glucose responses during an OGTT are not sufficient to overcome the underlying defects in glucose metabolism in obesity and diabetes.

Isotopic decay of urinary or plasma 3-methylhistidine as a potential biomarker of pathologic skeletal muscle loss.

BACKGROUND: Skeletal muscle loss accompanying aging or cancer is associated with reduced physical function and predicts morbidity and mortality. 3-Methylhistidine (3MH) has been proposed as a biomarker of myofibrillar proteolysis, which may contribute to skeletal muscle loss. METHODS: We hypothesized that the terminal portion of the isotope decay curve following an oral dose of isotopically labeled 3MH can be measured non-invasively from timed spot urine samples. We investigated the feasibility of this approach by determining isotope enrichment in spot urine samples and corresponding plasma samples and whether meat intake up to the time of dosing influences the isotope decay. RESULTS: Isotope decay constants (k) were similar in plasma and urine, regardless of diet. Post hoc comparison of hourly sampling over 10 h with three samples distributed over 10 or fewer hours suggests that three distributed samples over 5-6 h of plasma or urine sampling yield decay constants similar to those obtained over 10 h of hourly sampling. CONCLUSION: The findings from this study suggest that an index of 3MH production can be obtained from an easily administered test involving oral administration of a stable isotope tracer of 3MH followed by three plasma or urine samples collected over 5-6 h the next day.

Bioavailability of magnesium diglycinate vs magnesium oxide in patients with ileal resection.

BACKGROUND: Patients who have undergone ileal resection are at risk for developing magnesium depletion/deficiency because of poor absorption and decreased intake as well as increased endogenous losses. Magnesium repletion is difficult to accomplish because of the cathartic action of most oral magnesium supplements at therapeutic doses. The results of in vitro and in situ studies show that magnesium diglycinate (chelate) represents a highly available form of magnesium that is absorbed in part as an intact dipeptide in the proximal small intestine. METHODS: We conducted a double-blind, randomized crossover trial with 12 patients who had ileal resections in order to compare the bioavailability of a 100-mg dose of 26Mg-labeled chelate with MgO in this patient population. RESULTS: For the patient group as a whole, 26Mg absorption was low but was not different for the two supplements (23.5% vs 22.8% for magnesium chelate and MgO, respectively). However, 26Mg absorption was substantially greater from the chelate (23.5% vs 11.8%; p < .05) in the four patients who showed the greatest impairment of magnesium absorption with MgO and was better tolerated by all patients. Peak isotope enrichment also occurred significantly earlier after 26Mg chelate than after 26MgO ingestion (mean difference 3.2 +/- 1.3 hours; p < .05), and the area under the enrichment vs time curve was greater after chelate ingestion (p < .05). CONCLUSIONS: Data from this study support the suggestion that some portion of magnesium diglycinate is absorbed intact, probably via a dipeptide transport pathway. Magnesium diglycinate may be a good alternative to commonly used magnesium supplements in patients with intestinal resection.

Dysprosium as a nonabsorbable marker for studies of mineral absorption with stable isotope tracers in human subjects.

Two studies were conducted to determine if dysprosium (Dy) could be used as a quantitative fecal marker for studies of zinc-70 (70Zn), copper-65 (65Cu) and magnesium-26 (26Mg) absorption in humans. In the first experiment, Dy excretion was shown to be complete (104 +/- 9%; mean +/- SD, n = 6) and the kinetics of fecal Dy excretion closely paralleled that of 70Zn but not 65Cu. Because of the similarity in 70Zn and Dy excretion kinetics, a method for estimating 70Zn absorption was developed which used 70Zn and Dy data from only the first two stools passed after isotope administration. Average estimates of 70Zn absorption based on the two-stool (partial pool) vs total pool (5-day composite) method were not different (28.0 +/- 5.2 vs 24.4 +/- 4.1%, respectively; means +/- SEM; p > 0.10). In the second study, the same questions was addressed relative to 26Mg absorption. 26Mg and Dy also exhibited nearly identical excretion patterns. Average estimates of 26Mg absorption based on the partial pool vs total pool method were comparable yielding mean values of 22.7 +/- 3.4 vs 23.2 +/- 2.5% and 26.1 +/- 1.8 vs 24.3 +/- 1.8%, respectively, from magnesium-26 oxide (26MgO) and 26Mg glycinate. Advantages and limitations of the partial pool method for estimating mineral absorption are discussed.

Tolerability of iron: a comparison of bis-glycino iron II and ferrous sulfate.

The tolerability of supplemental iron in the chelated form of bis-glycino iron II was compared with that of ferrous sulfate in a randomized, double-blind, cross-over trial. Both iron formulations were prepared to deliver 50 mg elemental iron in each capsule; the capsules for both formulations were identical in appearance and weight. Each supplement was taken once daily before breakfast for two weeks. The incidence and severity of adverse side effects were not statistically different for the two preparations. However, of the 38 women evaluated, 14 (37%) experienced moderate-to-severe side effects only while taking the sulfate formulation compared to eight (21%) who experienced similar side effects only while taking the chelate formulation; the remaining 16 women had the same symptom profile with both preparations. This tendency for the chelate to be better tolerated was observed for the symptoms of bloating, constipation, and nausea. In addition, a significant (P less than 0.05) number of women preferred the chelate to the sulfate formulation. This preference appeared to be related to the lower number of side effects experienced with the chelate.

The effect of carbohydrates in milk on the absorption of calcium by postmenopausal women.

The purpose of this investigation was to determine if the presence of carbohydrate in milk, either lactose or its hydrolysis products, enhance the bioavailability of calcium (Ca) in milk. Two studies were performed. In study A, fractional Ca absorption was measured in 11 lactose-tolerant postmenopausal women after an oral dose of 47Ca-equilibrated milk formula containing no carbohydrate (NOCHO), lactose (LACTOSE), or an equivalent amount of glucose plus galactose (SUGAR); all participated in three absorption studies in random order. The NOCHO formula contained 10.0 g protein and 217 mg Ca from a combination of milk mineral and protein isolates; the LACTOSE and SUGAR formulae contained in addition 12 g lactose or 6 g glucose plus 6 g galactose, respectively. In study B, fractional Ca absorption was measured in five postmenopausal women after an oral dose of 47Ca-equilibrated skim milk (217 mg Ca) and lactase-treated milk, each with sufficient carbohydrate added to equal 12 g. For both studies, the increase in forearm radioactivity 4 and 8 hours after oral 47Ca administration relative to the increase observed after IV administration was used to estimate fractional Ca absorption. The addition of lactose but not glucose plus galactose to the NOCHO formula enhanced Ca absorption (p less than 0.05). Fractional absorption at 4 hours was 0.386 from the LACTOSE formula compared with 0.310 for both the NOCHO and SUGAR formulae. Those individuals with the lowest absorption in the absence of carbohydrate had the greatest increase with lactose. In contrast, Ca absorption was the same from skim milk as from lactase-treated skim milk (study B).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of Mg nutriture on the dynamics of administered 25Mg exchange in vivo in the rat.

The effect of Mg nutriture on Mg exchange and interorgan distribution was studied in adult rats ten days after a single I.P. dose of (25)Mg ( approximately 5 mg). First the effects of level of Mg intake (0.25, 0.05, or 0.01% Mg) on standard measures of Mg nutriture were studied for 62d to fully document the Mg status of the adult rats. The Mg-deficient diet led to a reduction in plasma, erythrocyte and urine Mg concentration but the only tissues affected were kidney and bone; no outward signs of deficiency were observed. At this point, the 4 remaining rats from each diet group received a single dose of (25)Mg and were killed 10d later. Unlike measures of total Mg content, Mg restriction was observed to significantly alter the distribution of isotope within the soft tissue compartment. The proportion of retained isotope accumulated by soft tissues other than skeletal muscle increased. Because this was not true for skeletal muscle, exogenous (25)Mg label was diverted to more metabolically active tissues during Mg restriction. The apparent Mg exchangeable pool (MgEP) size, determined by in vivo stable isotope dilution, reflected this difference in skeletal muscle (25)Mg accumulation; MgEP size was 39% lower in Mg restricted (0.01% Mg) compared to control (0.05% Mg) rats. The pool of exchangeable Mg in bone was also reduced by Mg restriction but, unlike the soft tissue compartment, the reduction in bone exchangeable Mg was quantitatively similar to the reduction in total Mg content.

Feasibility of using the stable isotope 25Mg to study Mg metabolism in infants.

The feasibility of using isotopic techniques to study Mg absorption and metabolism was explored in three full-term human infants. 25Mg (98.8 atom %) was administered orally as an in vivo tracer. Fractional 25Mg absorption, isotope retention, endogenous fecal Mg losses, and apparent Mg exchangeable pool size were then determined under three conditions of isotope administration: 1) 20 mg 25Mg, with single feeding; 2) 20 mg 25Mg, distributed over a 24-h period; and 3) 60 mg 25Mg, over a 24-h period. Mg isotope ratios were determined by inductively coupled plasma mass spectrometry. Fractional absorption was increased in all three infants after distributed versus bolus administration at the 20 mg dose; mean (+/- SD) fractional absorption was 64.0 +/- 3.9 versus 54.3 +/- 5.9%, respectively. 25Mg retention was also more in all three infants after distributed administration (55.8 +/- 3.0 versus 44.3 +/- 1.3% of dose). At the 60-mg 25Mg dose, compared to 20 mg, fractional absorption was reduced but absolute isotope absorption more than doubled in all infants; urine isotope losses represented a similar fraction of the absorbed dose, thus, 25Mg retention also more than doubled. Compared to the results of the isotope studies, net Mg absorption and balance were uninfluenced by total Mg intake. Isotope retention with distributed isotope administration resulted in measurable isotopic enrichment of plasma and erythrocytes at 72 h (i.e. plasma isotope enrichment was 6.3-10.2 and 19.2-23.5% for the 20- and 60-mg dose, respectively). With these doses, apparent Mg exchangeable pool size ranged from 5.5 to 7.6 mmol/kg body wt; these values showed a decrease with age both within and between infants.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of lactose or its component sugars on jejunal calcium absorption in adult man.

The effect of lactose vs glucose plus galactose on jejunal calcium absorption was studied in 10 subjects using a triple-lumen perfusion technique. In each, 30 cm of jejunum was perfused with two test solutions. The comparisons made were lactose (Lac) vs mannitol (Man), Lac vs glucose and galactose (GG), and Man vs GG. Compared with Man, Lac, and GG caused a significant increase in net water and sodium absorption and luminal calcium concentration. In subjects receiving both Lac and GG, water and sodium absorption were greater with GG. The only statistically significant increase in net calcium absorption occurred with Man vs GG in which water absorption increased from 16 to 350 mL.h-1.30 cm-1. However, by use of data from all test solutions, water and sodium absorption were found to be significantly correlated with calcium absorption (p less than 0.05). These results suggest that lactose or its component sugars enhance jejunal calcium absorption in proportion to their effect on fluid absorption.

Intestinal absorption of Ca(H2PO4)2 and Ca citrate compared by two methods.

The purpose of this study was to compare the absorption of calcium from two soluble Ca salts and determine if the oral Ca load test can be used as a simple measure of relative Ca bioavailability. Eight normal subjects ingested 750 mg Ca as solution of Ca(H2PO4)2 or Ca citrate (two occasions) tagged with 47Ca tracer. Absorption of Ca from the two salts was estimated from both the increase in forearm radioactivity and rise in urinary Ca (oral Ca load test). Both measures indicated that Ca was absorbed at least twice as well from Ca citrate as from Ca(H2PO4)2. However, the increment in urinary Ca 2-4 h after the oral load correlated with fractional absorption when only Ca citrate (r = 0.803, p less than 0.02) was ingested. For group comparisons the oral Ca load test is a rough index of Ca availability but cannot substitute for more direct measures of absorption in an individual.

Renal transport and metabolism of nicotinic acid.

Renal metabolism and brush-border transport of nicotinic acid were studied in renal cortical slices and brush-border membrane vesicles exposed to a physiological concentration of vitamin (2.2-3.5 microM). Vesicle transport of [3H]nicotinic acid was found to be Na+ dependent and concentrative. The presence of a Na+ gradient resulted in a fivefold increase in the rate of nicotinic acid uptake over that observed with mannitol and caused a transient nicotinic acid accumulation two- to fourfold above the equilibrium value. The effects of membrane potential, pH, and elimination of Na+-H+ exchange were also studied. Cortical slices and isolated tubules exposed to 2.2 microM [14C]nicotinic acid took up vitamin and rapidly metabolized most of it to intermediates in the Preiss-Handler (J. Biol. Chem. 233: 488-493, 1958) pathway for NAD biosynthesis; little free nicotinic acid was detectable intracellularly. The replacement of Na+ with Li+ in the bathing medium reduced total accumulation of 14C label primarily as a result of reduced nicotinic acid uptake. Cortical tissue concentrated free nicotinic acid only when the involved metabolic pathways were saturated by levels of nicotinic acid far in excess of what occurs in vivo.

The effect of diets high in fat and/or fiber on colonic absorption of DMH in the rat.

The possibility that long-term feeding of diets high in fat or fiber could alter the colonic mucosa and subsequent colonic absorption of 1,2-dimethylhydrazine (DMH) in situ was examined in the rat model. Male Sprague-Dawley rats were fed one of four experimental diets for six weeks prior to studies of DMH absorption and bile acid excretion; dietary treatments consisted of two levels of fat (12 and 47% of calories from corn oil) fed at each of two levels of fiber (plus or minus 15% wheat bran). Two sets of DMH absorption studies (Studies 1 and 2) were performed; the first used a 10- and the second a 20-minute test period. In Study 1, DMH absorption was greater in those animals that had been fed the high level of corn oil when additional fiber was not present in the diet. When a longer absorption period was used (Study 2), this effect of diet on DMH absorption was not apparent. The level of fiber, not the fat intake, altered bile acid excretion. Bile acid concentration (mg/g dry wt) decreased with added fiber, whereas total bile acid excretion (mg/day) increased. These results indicate that high levels of dietary fat may result in small increases in DMH absorption which are unrelated to changes in bile acid concentration.

Effective use of renal cortical slices in transport and metabolic studies.

The uptake and metabolism of two water-soluble vitamins were measured in rat renal cortical slices, isolated tubules, and vesicles of the brush-border and basolateral cell membranes to determine (a) whether it is possible to produce slices that have open tubules and, (b) whether slices and tubules metabolize vitamins similarly. Transport of ascorbic acid is sodium-dependent in slices and in brush-border vesicles but is sodium-independent in basolateral vesicles, suggesting that the brush-border membrane of slices is accessible to components of the bathing solution. Nicotinic acid was metabolized similarly (97-98%) in both slices and isolated tubules. Oxygen consumption by slices maintained in a closed chamber was constant as pO2 decreased from 88% to 58%. Slices are concluded to be a suitable model for transport and metabolic studies providing that care is taken in their preparation and use.

Nicotinamide uptake and metabolism by chick intestine.

Intestinal uptake and metabolism of nicotinamide (NAm) were studied in isolated epithelial cells and in isolated segments in situ at a physiological concentration of [14C]NAm (11.7 microM). [14C]NAm was rapidly taken up from the bathing medium and largely metabolized to [14C]NAD by the isolated cells. Total accumulation of 14C label was energy dependent and saturable at higher concentrations of NAm (148 and 351 microM). In contrast, the tissue content of NAm was unaffected by metabolic inhibitors, and the bathing media NAm rapidly equilibrated with intracellular space at all levels of NAm. NAm was converted directly to NAD via the intermediate nicotinamide mononucleotide (NMN); nicotinic acid was not an intermediate in this conversion and was a less efficient precursor of NAD. NAm absorption in vivo was substantial, 30.6% of dose after 10 min. Also, data on NAm entry into the mucosa and subsequent metabolism in vivo supported the in vitro observations. Exogenous NMN reduced NAm entry into the mucosal cells both in vivo and in vitro; the effect was specific to NAm. This is the only suggestion to date that NAm entry might proceed by some form of specialized transport process.

Effects on Ca and P metabolism in humans by adding meat, meat plus milk, or purified proteins plus Ca and P to a low protein diet.

The effects on calcium and phosphorus metabolism of adult man by adding meat or meat plus dairy products to a diet low in protein (55 g), calcium (590 mg), and phosphorus (890 mg) were determined. When the low protein diet was consumed, the subjects retained a mean of 20 mg calcium daily but lost 106 mg phosphorus. The addition of meat which increased protein and phosphorus to 146 g and 1660 mg, respectively, caused calcium retention to decrease from 19 to -17 mg but phosphorus retention to increase from 106 to 55 mg. When the meat plus dairy diet high in protein (146 g), calcium (1370 mg), and phosphorus (2060 mg) was consumed the subjects retained substantial amounts of calcium (101 mg) and phosphorus (177 mg). The simulated diets high in purified proteins and supplemented with calcium and phosphorus affected calcium retention in a manner similar to the meat and meat plus dairy diets, but they had a marked negative effect on phosphorus retention; this indicates that supplements of calcium gluconate were well utilized but that those of monopotassium phosphate were not. The results obtained on urinary sulfate, acid, cyclic AMP and hydroxyproline support the conclusions made from the calcium and phosphorus data.

Renal acid, urinary cyclic AMP, and hydroxyproline excretion as affected by level of protein, sulfur amino acid, and phosphorus intake.

Two 51-day human studies were conducted to investigate the effects of level of protein and phosphorus intake on the various components of renal acid excretion and on urinary sulfate, cyclic AMP and hydroxyproline; the role of the sulfur amino acids (Saa) of the protein was also evaluated. Dietary treatments included: 1) a 50 g protein diet; 2) a 150 g protein diet; and 3) a 50 g protein diet plus Saa to equal that of the 150 g protein diet, each given at 2 levels of phosphorus (1010 and 2525 mg). Calcium intake was 500 mg. Subjects were 16 young adult males. The results are discussed in relationship to calcium data previously reported (1, 2). Changes in renal acid and calcium excretion are not directly related for these reasons: a) the Saa accounted for all of the protein-induced increase in urinary sulfate and acid but for only 43% of the increase in urinary calcium and b) the acid phosphate supplement decreased urinary calcium but increased total acid excretion. The phosphorus supplement increased cyclic AMP but not hydroxyproline excretion. In fact, protein and Saa caused increases in hydroxyproline that were greatly reduced by the phosphorus supplement. Increases in urinary hydroxyproline and calcium were well correlated indicating that, at low calcium intakes, protein or Saa-induced increases in urinary calcium result in increased bone resorption which is reduced by the administration of phosphorus.

Protein-induced hypercalciuria.

Under controlled dietary conditions the level of dietary protein has a profound and sustained effect on urinary calcium and calcium retention of man. Young adults achieve calcium balance at low intakes of 500 mg calcium and 700 to 1,000 mg phosphorus when protein intake is 50 g. Large calcium losses occur at the same calcium and phosphorus intakes when the protein intake is increased approximately threefold. The protein-induced hypercalciuria is due mainly to a decrease in fractional renal tubular reabsorption of calcium, although an increase in glomerular filtration rate is also involved. The changes in kidney function appear to result from the catabolism of excess dietary sulfur amino acids to sulfate and the subsequent excretion of sulfate in the urine. An increase in both protein and phosphorus intakes has a much less dramatic effect on urinary calcium and calcium retention than an increase in protein intake alone. An increase in dietary phosphorus greatly reduces urinary calcium by increasing the fractional renal tubular reabsorption of calcium. It appears therefore that high protein intakes may increase the requirements for both calcium and phosphorus.