Fructose and Lactose Intolerance and Malabsorption Testing
Fructose and Lactose Intolerance and Malabsorption Testing
Patient characteristics are shown in Table 1. Seventy-six per cent of the 1372 patients were of Northern European and 19% of Mediterranean European Caucasian descent. Of these patients, the following subgroups were defined according to the Rome III criteria: Irritable Bowel Syndrome (n = 212), comprised of IBS with constipation (IBS-c, n = 37), IBS with diarrhoea (IBS-d, n = 67), IBS with alternating constipation and diarrhoea (IBS-m, n = 94) and IBS unclassified (IBS-u, n = 14), Functional Dyspepsia(n = 606), comprised of FD with postprandial distress (FD-ppd, n = 368) and FD with epigastric pain syndrome (FD-eps, n = 238), and Functional Bloating (n = 109).
The prevalence of fructose, lactose and both intolerances in all FGID patients was 60.4%, 50.5% and 33.1% respectively. In Northern European and Mediterranean Caucasians, 61.0% and 59.4% had fructose intolerance (not significant-N.S.), 47.8% and 53.6% had lactose intolerance (P < 0.01), and 33.2% and 29.5% had both intolerances (N.S.). Of males and females, 57.1% and 61.7% had fructose intolerance (N.S.), 43.6% and 53.3% had lactose intolerance (P < 0.01), and 27.6% and 35.2% had both intolerances (P < 0.05). Fructose was more common than lactose intolerance in all FGID subgroups (P < 0.001)(Figure 1), with no differences between FGID groups, except for more lactose and less fructose intolerance in constipated IBS (IBS-C) than in other subgroups (P < 0.05). 14.1% of patients with lactose intolerance and 6.9% of patients with fructose intolerance correctly suspected the target of their intolerance before breath testing.
(Enlarge Image)
Figure 1.
Prevalence of fructose and lactose intolerances in Rome III-defined Irritable Bowel Syndrome (IBS) (n = 212), Functional Dyspepsia (FD) (n = 606), Functional Bloating (FB) (n = 109) and their subgroups, IBS-c: IBS with constipation (n = 37), IBS-d: IBS with diarrhoea (n = 67), IBS-m: IBS with alternating constipation and diarrhoea (n = 94), IBS-u: unclassified IBS (n = 14), FD-ppd: Functional Dyspepsia with postprandial distress (n = 368), FD-eps: Functional Dyspepsia with epigastric pain syndrome (n = 238) and FB: Functional Bloating (n = 109).
The prevalence of non-GI and specific GI symptoms and related aspects of the medical history were compared across intolerance groups (Table S1). Overall, patients with any intolerance had more symptoms than those without (P < 0.001). Patients with both intolerances had significantly more problems with concentration, joint and muscle pain, nausea, gastro-oesophageal reflux and allergic reactions than those with no intolerances and generally also than patients with only one intolerance (Table S1). When comparing patients with either fructose or lactose intolerance with patients with no intolerances, very similar, albeit less prominent, differences emerged (Table S1).
The incidence of symptoms during fructose and lactose breath tests is shown in Figure 2. Flatulence, bloating and abdominal fullness were predominant in >50% of patients. Fifty-eight per cent of patients complained of at least one central nervous system effect, with fatigue topping the list. Symptom incidences were similar between both intolerance tests. The time-to-maximum symptom score was 115.3 ± 118 min with fructose and 131.1 ± 118 min with lactose (P < 0.001). Using a test cut-off time of 3 h instead of 5 h, 16% of fructose and 23% of lactose intolerance results would have changed from positive to negative.
(Enlarge Image)
Figure 2.
Percentages of patients with Functional Gastrointestinal Disorders (FGID) with symptoms provoked during fructose or lactose breath testing (n = 1372).
The incidence of several of the most commonly evoked symptoms during breath testing, specifically bloating, diarrhoea, abdominal pain, gastro-oesophageal reflux, tiredness, muscle pain and diminished concentration, correlated with patients' FGID symptoms (r = 0.34–0.51, all P < 0.005).
Table 2 shows the prevalence and overlap of malabsorption and intolerance in FGID and its subgroups. Malabsorption alone, i.e. with a negative intolerance test, occurred in 4.3% of fructose, 3.4% of lactose and 3% of both tests. Intolerance alone, i.e. with a negative malabsorption test, was seen in 20.0% of fructose, 22.4% of lactose and 20.2% of both tests, with no significant differences between the FGID subgroups.
Malabsorption was most frequently defined by a combination of supra-threshold H2 and CH4 concentrations (Table 3). Isolated elevation of CH4 was seen in 4.1% of patients following fructose and in 4.9% after lactose ingestion using the standard threshold of a CH4 increase of >10 ppm above baseline. Table 3 shows malabsorption rates using alternative CH4 thresholds.
H2 and CH4 peak concentrations correlated with the severity of bloating (r = 0.41, r = 0.43 respectively), abdominal pain (r = 0.35, r = 0.33 respectively) and diarrhoea (r = 0.5, r = 0.45 respectively)(all P < 0.001) during fructose and lactose (r = 0.53, r = 0.52; r = 0.48, r = 0.48; and r = 0.61, r = 0.59, respectively, all P < 0.0001) testing. The time-to-peak H2 and CH4 concentrations were 107.7 ± 71 min and 107.3 ± 76 min with fructose, and 164.2 ± 105 min and 168.5 ± 106 min with lactose respectively (both P < 0.001 vs. fructose). Peak concentrations of H2 and CH4 were reached after 3 h in 10.1% and 37.7% of fructose tests and in 9.8% and 33.8% of lactose tests respectively. There were no significant correlations between H2 and CH4 peak concentrations and any FGID symptoms. Peak concentrations of H2 >20 ppm in the first 60 min, so-called early rises in breath hydrogen, were seen in 12.9% of patients following fructose and in 6.0% of patients following lactose ingestion.
In patients with fructose or lactose malabsorption, as defined by any of the H2 or CH4 thresholds, diarrhoea was more common than constipation (all P < 0.05) (Figure 3). Conversely, patients with diarrhoea and constipation had a similar prevalence of malabsorption demonstrated by isolated elevation of H2 (14.5% and 11.3%) and CH4 (1.2% and 1.2%) concentrations following fructose and lactose ((7.7% and 6.5%) and (1.4% and 1.6%)) respectively. Furthermore, a majority (69%) of IBS-C patients did not have elevated CH4 levels after either sugar.
(Enlarge Image)
Figure 3.
Percentages of patients with Functional Gastrointestinal Disorders (FGID) with fructose (n = 613) or lactose (n = 432) malabsorption, i.e. an increase of H2 > 20 ppm or CH4>10 ppm over baseline, with diarrhoea or constipation. *P < 0.05 constipation vs. diarrhoea for both fructose and lactose.
Complete outcomes were available in 237 of the 312 patients (76%) with intolerances who received standardised dietary counselling once it was initiated. Thirty-six patients declined dietary counselling and 39 dropped out of the dietary programme and were lost to follow-up. Clinical characteristics did not differ between those having discontinued or completed the programme. Adequate symptomatic relief after 6–8 weeks was achieved in 84% of all patients with fructose intolerance and in 86% when fructose malabsorption was present with intolerance. Respective results for lactose intolerance were 89% and 90%. Eight-five per cent of all patients reported adequate dietary compliance. Adequate relief rates were 85% and 96% in patients with diarrhoea and bloating, respectively, compared to 51% in those patients with constipation (P < 0.01). Symptomatic relief >3 on the 10-point scale was achieved in 90% of all fructose and 94% of all lactose intolerant, and in 93% and 96% of those with concurrent malabsorption, respectively. Average symptom relief was between 6 and 7 on the 10-point scale for all the above subgroups, except in constipated patients where the average was 3 (data not shown).
Results
Patient characteristics are shown in Table 1. Seventy-six per cent of the 1372 patients were of Northern European and 19% of Mediterranean European Caucasian descent. Of these patients, the following subgroups were defined according to the Rome III criteria: Irritable Bowel Syndrome (n = 212), comprised of IBS with constipation (IBS-c, n = 37), IBS with diarrhoea (IBS-d, n = 67), IBS with alternating constipation and diarrhoea (IBS-m, n = 94) and IBS unclassified (IBS-u, n = 14), Functional Dyspepsia(n = 606), comprised of FD with postprandial distress (FD-ppd, n = 368) and FD with epigastric pain syndrome (FD-eps, n = 238), and Functional Bloating (n = 109).
Prevalence of Lactose and Fructose Intolerance During Testing and Association With Clinical Symptoms
The prevalence of fructose, lactose and both intolerances in all FGID patients was 60.4%, 50.5% and 33.1% respectively. In Northern European and Mediterranean Caucasians, 61.0% and 59.4% had fructose intolerance (not significant-N.S.), 47.8% and 53.6% had lactose intolerance (P < 0.01), and 33.2% and 29.5% had both intolerances (N.S.). Of males and females, 57.1% and 61.7% had fructose intolerance (N.S.), 43.6% and 53.3% had lactose intolerance (P < 0.01), and 27.6% and 35.2% had both intolerances (P < 0.05). Fructose was more common than lactose intolerance in all FGID subgroups (P < 0.001)(Figure 1), with no differences between FGID groups, except for more lactose and less fructose intolerance in constipated IBS (IBS-C) than in other subgroups (P < 0.05). 14.1% of patients with lactose intolerance and 6.9% of patients with fructose intolerance correctly suspected the target of their intolerance before breath testing.
(Enlarge Image)
Figure 1.
Prevalence of fructose and lactose intolerances in Rome III-defined Irritable Bowel Syndrome (IBS) (n = 212), Functional Dyspepsia (FD) (n = 606), Functional Bloating (FB) (n = 109) and their subgroups, IBS-c: IBS with constipation (n = 37), IBS-d: IBS with diarrhoea (n = 67), IBS-m: IBS with alternating constipation and diarrhoea (n = 94), IBS-u: unclassified IBS (n = 14), FD-ppd: Functional Dyspepsia with postprandial distress (n = 368), FD-eps: Functional Dyspepsia with epigastric pain syndrome (n = 238) and FB: Functional Bloating (n = 109).
The prevalence of non-GI and specific GI symptoms and related aspects of the medical history were compared across intolerance groups (Table S1). Overall, patients with any intolerance had more symptoms than those without (P < 0.001). Patients with both intolerances had significantly more problems with concentration, joint and muscle pain, nausea, gastro-oesophageal reflux and allergic reactions than those with no intolerances and generally also than patients with only one intolerance (Table S1). When comparing patients with either fructose or lactose intolerance with patients with no intolerances, very similar, albeit less prominent, differences emerged (Table S1).
The incidence of symptoms during fructose and lactose breath tests is shown in Figure 2. Flatulence, bloating and abdominal fullness were predominant in >50% of patients. Fifty-eight per cent of patients complained of at least one central nervous system effect, with fatigue topping the list. Symptom incidences were similar between both intolerance tests. The time-to-maximum symptom score was 115.3 ± 118 min with fructose and 131.1 ± 118 min with lactose (P < 0.001). Using a test cut-off time of 3 h instead of 5 h, 16% of fructose and 23% of lactose intolerance results would have changed from positive to negative.
(Enlarge Image)
Figure 2.
Percentages of patients with Functional Gastrointestinal Disorders (FGID) with symptoms provoked during fructose or lactose breath testing (n = 1372).
The incidence of several of the most commonly evoked symptoms during breath testing, specifically bloating, diarrhoea, abdominal pain, gastro-oesophageal reflux, tiredness, muscle pain and diminished concentration, correlated with patients' FGID symptoms (r = 0.34–0.51, all P < 0.005).
Prevalence of Lactose and Fructose Malabsorption and the Relationship With Intolerance During Testing and Clinical Symptoms
Table 2 shows the prevalence and overlap of malabsorption and intolerance in FGID and its subgroups. Malabsorption alone, i.e. with a negative intolerance test, occurred in 4.3% of fructose, 3.4% of lactose and 3% of both tests. Intolerance alone, i.e. with a negative malabsorption test, was seen in 20.0% of fructose, 22.4% of lactose and 20.2% of both tests, with no significant differences between the FGID subgroups.
Malabsorption was most frequently defined by a combination of supra-threshold H2 and CH4 concentrations (Table 3). Isolated elevation of CH4 was seen in 4.1% of patients following fructose and in 4.9% after lactose ingestion using the standard threshold of a CH4 increase of >10 ppm above baseline. Table 3 shows malabsorption rates using alternative CH4 thresholds.
H2 and CH4 peak concentrations correlated with the severity of bloating (r = 0.41, r = 0.43 respectively), abdominal pain (r = 0.35, r = 0.33 respectively) and diarrhoea (r = 0.5, r = 0.45 respectively)(all P < 0.001) during fructose and lactose (r = 0.53, r = 0.52; r = 0.48, r = 0.48; and r = 0.61, r = 0.59, respectively, all P < 0.0001) testing. The time-to-peak H2 and CH4 concentrations were 107.7 ± 71 min and 107.3 ± 76 min with fructose, and 164.2 ± 105 min and 168.5 ± 106 min with lactose respectively (both P < 0.001 vs. fructose). Peak concentrations of H2 and CH4 were reached after 3 h in 10.1% and 37.7% of fructose tests and in 9.8% and 33.8% of lactose tests respectively. There were no significant correlations between H2 and CH4 peak concentrations and any FGID symptoms. Peak concentrations of H2 >20 ppm in the first 60 min, so-called early rises in breath hydrogen, were seen in 12.9% of patients following fructose and in 6.0% of patients following lactose ingestion.
Breath Gases and Stool Patterns
In patients with fructose or lactose malabsorption, as defined by any of the H2 or CH4 thresholds, diarrhoea was more common than constipation (all P < 0.05) (Figure 3). Conversely, patients with diarrhoea and constipation had a similar prevalence of malabsorption demonstrated by isolated elevation of H2 (14.5% and 11.3%) and CH4 (1.2% and 1.2%) concentrations following fructose and lactose ((7.7% and 6.5%) and (1.4% and 1.6%)) respectively. Furthermore, a majority (69%) of IBS-C patients did not have elevated CH4 levels after either sugar.
(Enlarge Image)
Figure 3.
Percentages of patients with Functional Gastrointestinal Disorders (FGID) with fructose (n = 613) or lactose (n = 432) malabsorption, i.e. an increase of H2 > 20 ppm or CH4>10 ppm over baseline, with diarrhoea or constipation. *P < 0.05 constipation vs. diarrhoea for both fructose and lactose.
Outcome of Dietary Advice
Complete outcomes were available in 237 of the 312 patients (76%) with intolerances who received standardised dietary counselling once it was initiated. Thirty-six patients declined dietary counselling and 39 dropped out of the dietary programme and were lost to follow-up. Clinical characteristics did not differ between those having discontinued or completed the programme. Adequate symptomatic relief after 6–8 weeks was achieved in 84% of all patients with fructose intolerance and in 86% when fructose malabsorption was present with intolerance. Respective results for lactose intolerance were 89% and 90%. Eight-five per cent of all patients reported adequate dietary compliance. Adequate relief rates were 85% and 96% in patients with diarrhoea and bloating, respectively, compared to 51% in those patients with constipation (P < 0.01). Symptomatic relief >3 on the 10-point scale was achieved in 90% of all fructose and 94% of all lactose intolerant, and in 93% and 96% of those with concurrent malabsorption, respectively. Average symptom relief was between 6 and 7 on the 10-point scale for all the above subgroups, except in constipated patients where the average was 3 (data not shown).
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