Experienced Gastrointestinal Side Effects Research Articles

Enteric-coated sodium bicarbonate supplementation improves high-intensity cycling performance in trained cyclists

PurposeEnteric-coated sodium bicarbonate (NaHCO3) can attenuate gastrointestinal (GI) symptoms following acute bicarbonate loading, although the subsequent effects on exercise performance have not been investigated. The purpose of this study was to examine the effects of enteric-coated NaHCO3 supplementation on high-intensity exercise performance and GI symptoms.MethodsEleven trained male cyclists completed three 4 km time trials after consuming; a placebo or 0.3 g∙kg–1 body mass NaHCO3 in enteric-coated or gelatin capsules. Exercise trials were timed with individual peak blood bicarbonate ion concentration ([HCO3–]). Blood acid–base balance was measured pre-ingestion, pre-exercise, and post-exercise, whereas GI symptoms were recorded pre-ingestion and immediately pre-exercise.ResultsPre-exercise blood [HCO3−] and potential hydrogen (pH) were greater for both NaHCO3 conditions (P < 0.0005) when compared to placebo. Performance time was faster with enteric-coated (− 8.5 ± 9.6 s, P = 0.044) and gelatin (− 9.6 ± 7.2 s, P = 0.004) NaHCO3 compared to placebo, with no significant difference between conditions (mean difference = 1.1 ± 5.3 s, P = 1.000). Physiological responses were similar between conditions, although blood lactate ion concentration was higher with gelatin NaHCO3 (2.4 ± 1.7 mmol∙L–1, P = 0.003) compared with placebo. Furthermore, fewer participants experienced GI symptoms with enteric-coated (n = 3) compared to gelatin (n = 7) NaHCO3.DiscussionAcute enteric-coated NaHCO3 consumption mitigates GI symptoms at the onset of exercise and improves subsequent 4 km cycling TT performance. Athletes who experience GI side-effects after acute bicarbonate loading may, therefore, benefit from enteric-coated NaHCO3 supplementation prior to exercise performance.

Two-Hour CGRP Infusion Causes Gastrointestinal Hyperactivity: Possible Relevance for CGRP Antibody Treatment.

The monoclonal antibodies against calcitonin gene-related peptide (CGRP) or its receptor are new antimigraine drugs from which many patients already benefit. Very few side effects have been reported from the antibody trials, including very few gastrointestinal (GI) side effects. The current data derive from a double-blind cross-over study of CGRP infusion for 2hours. We present the GI side effects of the infusion and raise the question if underreporting of GI symptoms in CGRP antibody trials has occurred. We also discuss why constipation may be more likely with CGRP receptor blockade than with CGRP neutralizing antibodies. Thirty healthy volunteers were recruited to receive a 2-hour infusion of CGRP 1.5µg/minutes on 2 different days. The participants were pretreated with sumatriptan tablets (2×50mg) 1day and with placebo the other day. During the infusion, the participants were asked about side effects including a detailed description about their GI symptoms. Clinical observations like flatulence, rumbling, and use of bedpan were also noted. After the infusion, the participants filled out a questionnaire about side effects at home until 12-hour after the infusion start. The study was conducted at the Danish Headache Center at Rigshospitalet Glostrup in the period February 2018 to July 2018. On both study days 93% (27/29 participants) experienced symptoms from the GI system during the infusion. Rumbling, stomach pain, nausea, diarrhea, and an urge to defecate were the most commonly experienced GI side effects. There was no difference in symptoms between placebo and sumatriptan pretreatment. We conclude that a 2-hour infusion of CGRP causes frequent and sometimes severe symptoms from the GI system. The symptoms are not antagonized by sumatriptan. More attention should be paid to constipation as a possible side effect of CGRP receptor antagonists.

Benefits of Calcium Supplements Are Too Small for Clinical Equipoise to Exist

In his article “The Calcium Supplement Controversy: Now What?” Dr Bauer suggests that there is clinical equipoise regarding the use of calcium supplements and that more clinical trials are needed.1 We think both these views are questionable. Clinical equipoise implies uncertainty as to whether the benefits of calcium outweigh the risks. The benefits of calcium have been clearly defined in a number of large clinical trials with fracture as a primary endpoint. Pooled analyses of these trials suggest a 12% reduction in total fractures with calcium2 but no reduction, and possibly an increase, in hip fracture risk in community-dwelling individuals.3, 4 A 12% reduction in relative risk translates into a very small absolute benefit for people at low-moderate risk of fracture. For a population with an average 10-year fracture risk of 20%, 10 in 100 people would sustain a fracture within 5 years. By taking calcium supplements for 5 years, the proportion with fracture would reduce to 8.8 in 100 people, so that about 1 in 100 people benefit from taking calcium. If the average 10-year fracture risk is 10%, about 1 in 200 people benefit from taking calcium for 5 years. Because the absolute benefit of calcium in preventing fractures is so small, the risks must also be very small for clinical equipoise to exist. However, many people experience adverse effects from taking calcium. At least 10% to 20% experience gastrointestinal side effects, such as constipation, which cause a significant number to stop the supplements. Less common side effects include hospital admissions for acute gastrointestinal symptoms,5 renal stones,6 myocardial infarction (MI),7, 8 stroke,8 and, rarely, hypercalcemia.9 In the study by Prince and colleagues, there were 24 more women with a hospitalization for acute gastrointestinal symptoms in the calcium group than in the placebo group, and 16 fewer women with a fracture.5, 10 In the Women's Health Initiative, there were 68 more women with a kidney stone in the calcium group, and 56 fewer women with a fracture.6 In our two meta-analyses, the cardiovascular risks of calcium were similar to7 or exceeded8 the benefits of calcium on fracture prevention. Thus, available evidence suggests that the small risk of significant side effects coupled with the moderate risk of minor side effects outweighs any small benefits on fracture prevention. Even if clinical equipoise does exist, further clinical trials are both difficult to justify and unlikely to be feasible. The effect on fracture risk is already known, so the main purpose of future trials would be to define the risk of adverse events such as cardiovascular events. Based on the incidence of events in our previous individual patient data meta-analyses (mean age 74 years, 77% female),7 a 5-year study with 90% power to detect a 20% increase in MI, allowing for 20% loss to follow-up, would need about 27,000 participants and 45,000 participants to detect a 15% increase in stroke. Using data from a younger cohort at lower risk (mean age 67 years, 93% female),8 the respective numbers would be 56,000 for MI and 108,000 for stroke. Depending on the study design, these numbers are likely conservative estimates. Such trials would be extremely expensive and logistically challenging. Furthermore, obtaining ethical approval and recruiting participants is likely to be difficult given that the primary purpose would be to define the risks of an intervention with very small absolute benefits. For these reasons, we think that further large clinical trials of calcium supplements are unlikely to be undertaken. Clinical practice must, therefore, be guided by the data from existing clinical trials, with all their limitations. All authors state that they have no conflicts of interest.

Role of different approaches to the abdominal retroperitoneum for aortic lymphadenectomy in patients with gynecological cancers

BackgroundParaaortic lymphadenectomy (PALN) is a standard part of many interventions, but currently there are no established care protocols effective in preventing gastro-intestinal (GI) symptoms. The aim of our study was to retrospectively evaluate patients with gynecologic cancers submitted to PALN, in order to evaluate if different approaches to the retroperitoneum could influence the radicality of the procedure and the onset of GI complications. MethodsWe divided 121 patients with gynecologic tumors submitted to PALN into 3 groups according the used right, left or combined left–right approach to the retroperitoneum, comparing the groups according the main surgical-pathological parameters, such as the number of nodes removed and the incidence and severity of GI complications. ResultsThe mean number of nodes removed did not significantly differ between the groups, while the mean number of positive nodes was significantly higher in combined approach. 39.8% of our patients experienced GI side effects, but those submitted to the combined approach had a significantly higher incidence of GI symptoms. ConclusionsOur data demonstrate that the choice of the retroperitoneal approach could be the most important feature for the appearance of post-operative GI side effects, even if there is no significant difference on the radicality of PALN performed retroperitoneal approach.

Erythromycin

Erythromycin

Tolerability of Enteric-Coated Didanosine Capsules Compared With Didanosine Tablets in Adults With HIV Infection

Background: A new enteric-coated (EC) didanosine (ddI) formulation (Videx EC; Bristol-Myers Squibb, Princeton, NJ, U.S.A.) may be better tolerated than the tablet form because it lacks the buffer component thought to be responsible for diarrhea and other gastrointestinal (GI) side effects. Objective: To evaluate the frequency and magnitude of GI side effects (nausea, bloating, GI upset, diarrhea, abdominal cramps, gas [flatus]) before and after switching the formulation of ddI, in study subjects who were experiencing one or more GI symptom(s) of at least moderate severity. Methods: A 6-week open label crossover study of current didanosine tablet users comparing daily symptom scores (7 point scale, 0 = absent to 6 = very severe) during weeks 1 to 2 (on tablets) to weeks 4 and 6 (on EC capsules). Formulation palatability and preference, lifestyle effects, and use of antidiarrheals or other medications for symptom relief were also assessed. Results: GI symptom scores (7-day means) on tablets were diarrhea 2.11, gas 2.00, bloating 1.23, abdominal cramps 0.74, GI upset 0.69, nausea 0.66. After switching to EC (week 4 and week 6), mean scores decreased for diarrhea (mean scores 0.99 week 4, 0.79 week 6), gas (0.95, 0.79), bloating (0.49, 0.32), abdominal cramps (0.21, 0.05), GI upset (0.16, 0.14), and nausea (0.32, 0.22). Severity of all GI symptoms was significantly reduced after 4 weeks on EC capsules (p < .01 by paired t-test). Negative impact of side effects on routine activities was significantly reduced (41% on tablet vs. 7% on EC; p < .01). All 42 study subjects preferred the EC form. Conclusions: According to patients' diary scores, switching to ddI in EC form significantly reduces nausea, bloating, GI upset, diarrhea, abdominal cramps, and gas for individuals who experienced GI side effects while taking the buffered tablet form. The striking tolerability advantages appear to support routine switching to EC for such patients and may suggest that widespread preferential selection of the EC form is appropriate to enhance didanosine tolerability and promote treatment adherence.

The acute effects of oral ethanol on the hypothalamic‐pituitary‐adrenal axis in normal human subjects

To evaluate the acute effects of oral ethanol on the hypothalamic-pituitary-adrenal axis in normal human subjects and, in particular, to examine the effect of background alcohol intake and gastrointestinal side-effects on this response. Plasma ethanol, cortisol, ACTH, corticotrophin-releasing hormone (CRH) and AVP were measured half-hourly for 4 hours following 1.1 ml/kg of 95% ethanol or placebo in a cross-over study. At least one week elapsed between each procedure. Twelve healthy non-alcoholic volunteers with a wide range of background alcohol intakes. Peptide hormones were measured by radioimmunoassay, cortisol by ELISA and blood ethanol by headspace gas chromatography. Results are expressed as mean +/- SEM. Blood ethanol levels peaked at one hour post ethanol ingestion. Three subjects developed significant gastrointestinal (GI) side-effects, with two vomiting and one experiencing moderate to severe nausea. There was no difference between peak blood ethanol levels in the groups with and without GI side-effects (34.5 +/- 2.4 mmol/l vs 34.3 +/- 1.7 mmol/l respectively). ACTH and cortisol rose in those subjects who experienced GI side-effects (P < 0.0001 for each). The remaining subjects had a tendency for ACTH and cortisol to be higher on the placebo day. The group with GI side-effects following ethanol administration had a significant rise in AVP (P < 0.02) that was synchronous with ACTH and cortisol. No consistent alcohol related changes were seen in peripheral CRH levels, although there was a significant increase over time on both active and placebo days (P < 0.0001). In the group with no GI side-effects, AVP did not significantly fall in the first half hour following ethanol, while a significant fall did occur following placebo (P < 0.05). Plasma renin activity was, however, increased by ethanol (P < 0.05). The background alcohol intake of the group with GI side-effects was significantly lower than the group without (18 +/- 7 vs 235 +/- 51 g/week, P < 0.05), but no hormonal response was seen in two subjects with a relatively low alcohol intake (< 100 g/week) who did not experience GI side-effects. Intoxicating levels of ethanol per se do not result in activation of the hypothalamic-pituitary-adrenal axis in humans. However, gastrointestinal side-effects induced by the ethanol do result in such activation, which appears to be mediated by AVP as the dominant ACTH secretagogue. One of the factors which influences the blood ethanol level at which GI side-effects occur appears to be background alcohol intake.