CONCLUSION

Chinese honeysuckle flower (Lonicerae), iberogast (STW 5, an ethanolic extract formula of nine botanicals), D-limonene, Artemisia asiatica, Curcumin, Quercetin, and vitamin E have been stated as botanicals or antioxidants for GORD.¹⁵⁴ A review article reported no published human studies for some botanicals, no beneficial effect in human trials, some agents not used as stand-alone treatment in the trial, and trials asides from the symptomatic effect have not attempted to measure factors such as changes in LOSP, erosive oesophageal healing or effect on gastric or oesophageal pH.¹⁵⁴

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2.8. 3 NON-PHARMACOLOGICAL MODALITIES (LIFESTYLE MODIFICATION) Multiple lifestyle recommendations have been offered as a potential approach to managing GORD symptoms, but in most instances, the supporting evidence is weak.⁷⁷ The lifestyle modifications include weight loss, tobacco cessation, avoidance of post-prandial recumbence, head of bed elevation, alcohol intake reduction, adoption of left lateral sleeping position, small meal sizes and avoidance of fatty and spicy meals.^7,45 There is evidence to support weight loss in overweight or obese patients and elevation of the head of the bed at night.^7,44,85 Asides these evidences, the current usage and associated success rate of other lifestyle measures are unknown. As a general recommendation, it would be impractical to apply the entire standard GORD “lifestyle recommendations”. Nonetheless, subsets of patients with GORD may benefit from specific lifestyle modifications, and common sense should prevail.

Lifestyle modification strategies are considered to be of some potential benefit and no proven harm, although not sufficiently effective in treatment as the sole initial or long-term therapy for GORD.^7,32 It has being considered reasonable, despite the lack of scientific evidence, to educate patients about various factors that may precipitate reflux.^31,122 Based on expert opinion, lifestyle modifications should be initiated and continued throughout the course of therapy in patients with a history that is typical of uncomplicated GORD as adjunctive therapy.7,18,44,45 This used to be the position of the Asia-Pacific Consensus on the management of GORD and the American Gastroenterological Association (AGA) until the recently published guideline of AGA in 2013.^122,155 Current recommendations are those of weight reduction in overweight and obese patients, head of bed elevation, and avoidance of meals 2-3 hours before bedtime.⁸⁵ The 2013 guideline did not recommend in the treatment of GORD, routine global elimination of food that trigger reflux (including chocolate, caffeine, alcohol, acidic and/or spicy foods). This is as a result of the conditional recommendation or low level of evidence.⁸⁵ It was however stated that selective elimination could be considered

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if patients note correlation with GORD symptoms and improvement with elimination. For example in patients with nocturnal symptoms, avoidance of postprandial recumbence for 3 – 4 hours, avoidance of a large evening meal, orchestrating the head-of –bed elevation, and efforts towards weight reduction will be encouraged.

Nowak et al in a survey of general practitioners (GPs) in North Queensland, Australia in 2005, reported that 76.5% of GPs recommended patients to avoid eating before laying down, avoidance of spicy food was 59.6%, and 11.0% gave postural advice.¹⁵⁶ The treatment was considered by 83.1% GPs to be effective for avoidance of eating before laying down, 58.1%

for avoidance of spicy foods, and 10.3% for postural advice amongst other responses.¹⁵⁶ Almost all GPs (98.8%) felt that at least some of their GORD patients could significantly reduce the severity and frequency of symptoms by modifying their lifestyle. However, almost half of these GPs (50.4%) felt that fewer than 10% of their GORD patients would be prepared to make these changes.

2.8.3.1 Effect of avoidance of spicy meals

The average daily chilli consumption in Asian people is 2.2 – 8g per person with a 5%

prevalence of GORD compared to 0.05 – 0.5g person in European and Americans with a 10 – 20% prevalence.2,3,83,157 Epidemiologic studies in Asian countries, including China, Iran, and Thailand, demonstrated lower heartburn/regurgitation symptom prevalence ratios compared to Western countries with a low prevalence of spicy food consumption, ironically.^83,158 A 24 - hour pH monitored study in Thailand (Asia), with a high prevalence of spicy food reported only acid regurgitation as the main GORD symptom contrary to GORD patients in Western countries.⁸³ Small studies suggested that a chronic ingestion of capsaicin containing chilli (2.5g/day for 5 – 6 weeks) can modify dyspepsia symptoms in functional dyspepsia patients and reflux symptoms in NERD.^159,160 Geratikornsupuk and Gonlachanvit still in Thailand and in a small study of 11 participants reported that the number of gastro-oesophageal reflux,

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percentage time pH < 4 in distal oesophagus, mean oesophageal and gastric pH, and gastro-oesophageal reflux symptoms were not different between standard meal and standard meal with red chilli (p > 0.05).¹⁵⁷ The 2.5g of chilli used was however less than the 5g consumed by Thai subjects. A previous smaller study reported that chronic chilli ingestion induces more gastro-oesophageal reflux.¹⁵⁷

Studies on average daily chilli consumption in Nigeria are lacking despite having hot and spicy stews in various proportions depending on the individual or community preferences.

2.8.3.2 Effect of late-evening meal and avoidance of recumbence for 3 - 4 hours postprandial

Postprandial reflux is common in patients with GORD.^77,79 Two studies that evaluated the effect of the timing of evening meal on 24-hour intragastric acidity in healthy volunteers showed different effects on nocturnal pH. Duroux et al in a study of early (6 PM) versus late (9pm) dinner intake demonstrated lower intragastric pH (median pH, 1.39 vs 1.67; p ≤ 0.001) in the later meal setting, but only between midnight and 7 AM.¹⁶¹ In another study by Lanzon-Miller et al on 10 healthy patients, however showed that nocturnal and 24-hour integrated intragastric acidity were unaffected by changes in the timing of the evening meal.¹⁶² In a small study that examined the effect of late-evening meals in GORD patients, Orr and Harnish measured oesophageal pH and symptoms in 20 patients during a late-evening meal on one night (consumed at 9pm) and a meal before 7pm on a subsequent evening. There was no difference between the two nights in terms of acid exposure, number of reflux episodes, and mean reflux episode duration.¹⁶³ However, the study results might have been confounded by the high fat meal consumed on both nights resulting in delayed gastric emptying. The strength of association between the occurrence of nocturnal reflux and late evening meals in other studies too have been limited by the confounding effect of the

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content of the evening meal (fatty meals) and anthropometric state of some participants (obesity).

It is generally recommended that patients with GORD refrain from eating within 3 hours of going to sleep.^7,45,85 Fujiwara et al performed a matched case-control study of 147 GORD patients and age- and sex-matched 294 controls without GORD symptoms during previous year under review.¹⁶⁴ The dinner-to-bed time defined as the time intervals until going to bed after finishing eating dinner, was examined by self-report questionnaire. After adjustment for smoking habits, drinking habits and BMI, shorter dinner-to-bed time was significantly associated with an increased odds ratio for GORD (p < 0.001). The odds ratio for patients whose dinner-to-bed time was less than 3 hours was 7.45 (95% CI 3.38 -16.4) compared with patients whose dinner-to-bed time was 4 hours or more. These observations were consistent in both patients with NERD and erosive oesophagitis. There was no significant difference in the dinner-to-bedtime intervals between NERD and erosive oesophagitis.

Studies examining the effect of late-evening meals in GORD patients in Nigeria are lacking.

The evidence to routinely recommend avoidance of late evening meals in patients with GORD remains incomplete and low. Current guideline (AGA) recommends that patients avoid eating meals with high fat content within 2-3 hours of reclining based on the improved nocturnal gastric acidity from case-control studies by Orr et al and Duroux et al.^85,163,164

2.8.3.3. Effect of lateral decubitus positions on GORD

A change in sleep position is reported as being beneficial to the health of people who suffer a range of medical conditions such as asthma, other respiratory illness, sleep apnoea, heartburn and chronic indigestion.⁸⁶ In GORD, several studies have shown that reflux is increased in patients in the right lateral decubitus position.^165,166 The reason for this phenomenon is not completely clear, but it may be related to increased transient LOS relaxations in the right position, or possibly that the gastro-oesophageal junction lies above the level of gastric acid

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in the left lateral position.^45,166 Laying on the left side has been shown to increase sphincter pressure and oesophageal pH. ⁴⁶ Specifically, total reflux time, average acid clearance, and LOS relaxations are significantly prolonged in patients lying on their right side compared with the left lateral decubitus position.^46,165,166

Studies examining the potential effect of right lateral decubitus position on reflux events have been confounded by the administration of high fat diets during the observational period. In a small study by Khoury et al, 10 subjects with supine reflux on ambulatory oesophageal monitoring exhibited a greater percentage of time pH < 4 (median, 18.1%; interquartile range [IQR], 4.4% – 44.4%), compared with time pH < 4 of 1.4% for the prone position (IQR, 0%

– 4.5%) and 0.9% for the supine position (IQR, 0% – 4.5%; P < .003) and longer median oesophageal clearance times, but all subjects were also fed a high fat dinner and bedtime snack.¹⁶⁵ In other small studies enrolling healthy subjects who were fed high fat meals, the right lateral decubitus position was associated with prolonged acid exposure ( 7.0% versus 2.0%, p < 0.03), greater number of transient lower oesophageal sphincter relaxations (6.5 versus 3.2 per hour, p < 0.03), and higher percentage transient lower oesophageal sphincter relaxations associated with reflux (57.0% versus 22.4%, p < 0.03) but not increased number of reflux episodes compared with the left supine position.¹⁶⁶ The results could have been confounded by the presence of an elevated BMI and high fat content of the meals.

Studies examining the potential effect of positional changes on reflux events are lacking in Nigeria.

If patients are going to have reflux when they lie down at night, the majority of these episodes will occur in the early phases of their sleep cycle, the first 2 hours.^56,167 Therefore, acid control through the day and at least the early part of the night with left lateral sleep positioning to reduce oesophageal exposure to refluxate should provide the most effective therapy. Despite evidence that the right lateral decubitus position can aggravate reflux, the

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practical aspects of this lifestyle modification (adoption of left lateral sleeping position) make it a challenge to implement in patients with GORD. Some patients may benefit by trying to start their sleep on the left side down, and perhaps a pillow can be placed behind them to enhance the likelihood that they will stay in that position for a longer time.

2.8.3.4 Effect of head of bed elevation

Lower oesophageal sphincter pressure has been shown to be higher at night compared with the daytime period.¹⁶⁵ The effect of HOB elevation on nocturnal reflux symptoms appears to be related to duration of reflux events rather than decreased frequency.⁷⁹ Counselling patients regarding head of bed (HOB) elevation is based on the theory that stomach contents containing acid will more likely reflux into the oesophagus while patients are lying flat. The height of the bed head elevation is critical and must be at least 6–8 inches (15–20 cm) to be at least minimally effective to prevent reflux of gastric contents.⁸⁵

The reported effect of different body positions (sitting, lying, and elevated HOB using 28cm blocks) showed significantly fewer reflux episodes, shorter reflux episodes, faster acid clearing, and fewer reflux symptoms in sleeping on a wedge (HOB elevation) compared with sleeping in the horizontal position suggesting a gravitation effect as a cause for the results.^77,92

Khan et al performed a clinical trial of symptomatic nocturnal reflux patients with documented recumbent (supine) reflux verified by oesophageal pH test who served as their control when they slept on a flat bed at baseline and subsequently utilized a 20 centimetre block for the head bed elevation.⁷⁹ Twenty of 24 (83.3%) patients with mean age of 36 ± 5.5 years completed the study. The mean percentage supine reflux time pH was > 4, acid clearance time, number of refluxes 5 min longer and symptom score on day 1 and day 7 were 15.0 ± 8.4 and 13.7 ± 7.2; p = 0.001, 3.8 ± 2.0 and 3.0 ± 1.6; p = 0.001, 3.3 ± 2.2 and 1.0 ± 1.2; p = 0.001, and 2.3 ± 0.6 and 1.5 ± 0.6; p = 0.04, respectively. The sleep disturbances

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improved in 13 (65%) patients. Head of bed elevation reduced oesophageal acid exposure and acid clearance time in nocturnal (supine) refluxers and led to some relief from heartburn and sleep disturbance.⁷⁹

Improvement in symptoms and reflux parameters is likely due to the effect of gravity in causing increased clearance of refluxed stomach contents. Reflux of acid is more injurious at night than during the day. At night, in a supine position it is easier for reflux to occur because gravity is not opposing the reflux as it does in the upright position during the day asides the reduced buffering effect by saliva. In addition, lack of effect of gravity allows the refluxed liquid to travel further up the oesophagus and remain in the oesophagus longer.⁷⁹The HOB elevation with foam wedge or blocks is an effective measure to improve the symptoms and physiologic variables in some patients with GORD and is recommended in patients with nocturnal GORD.⁸⁵ Khan et al reported that the beneficial effect in patients with major nocturnal reflux seems to be small when compared with proton pump inhibitor treatment.⁷⁹ 2.8.3.5 Effect of weight reduction

Weight reduction in overweight and obese patients (even in normal subjects) has been shown to correlate with a reduction in reported GORD symptoms.⁷⁸ A large case-control study based on the Nurses Health Cohort demonstrated a 40% reduction in frequent GORD symptoms for women who reduced their BMI by 3.5 kg/m² or more compared with controls.⁷⁸ Symptoms improve once there is a weight loss of 5% to 10%.⁷⁸ A mean loss of 12.4kg in 13weeks was reported.⁷⁸ Weight reduction has been strongly recommended for patients with BMI > 25 kg/m² or patients with recent weight gain.⁸⁵

2.8.3.6 Effect of other lifestyle modification modalities 2.8.3.6.1 Alcohol

Multiple differences exist between beverage types including alcohol content (lower in beer), volume (higher per serving for beer), and carbonation (present in beer but not liquor).⁸⁸

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Modest alcohol intake has been shown to induce reflux symptoms and decrease oesophageal pH in healthy individuals without GORD symptoms despite normal overall 24-hour pH measurements.⁸⁹ Randomized and cross-sectional studies have suggested an increased

prevalence of symptomatic reflux in alcohol users.^168-170 Wang et al reported reflux symptoms in 43% of heavy (≥ 210 g/wk) alcohol users compared with 16% of nondrinkers (OR, 2.85; 95% CI, 1.67-4.49; P < 0.01); however, large American and multinational cross-sectional studies have not shown similar associations.^77,171

White wine seems to induce more gastro-oesophageal reflux than red wine does (pH < 4:

white wine 13.2%, red wine 2.3%, tap water 0.9%).⁴⁵ Frequent alcoholic consumption (>7 drinks per week) worsens reflux.⁵⁶

In a case-control study that examined GORD outcomes in symptomatic alcoholic patients compared with matched control group without alcohol consumption, patients with GORD, and patients with nutcracker oesophagus, most alcoholic patients demonstrated LOS hypertension, high-amplitude oesophageal contractions, or non-peristaltic oesophageal contractions that improved after prolonged (> 6 months) alcohol abstinence but were not accompanied by improvements in oesophageal pH. Therefore, although oesophageal motility abnormalities were shown to improve after the cessation of alcohol use, there is insufficient evidence to support the direct effect of alcohol abstinence on pH or GORD symptoms, a position upheld by current AGA guideline.^77,85 Nonetheless, counselling for alcohol reduction and/or cessation for other health benefits should be carried-out at every encounter.

2.8.3.6.2 Carbonated beverages

Hamoui et al in a small clinical study demonstrated that in healthy individuals, ingestion of carbonated water, caffeinated cola, or caffeine-free cola reduced lower oesophageal sphincter pressure compared with tap water ingestion.¹⁷² However, a recent systematic review

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concluded that there was lack of evidence that consumption of carbonated beverages causes or provoke GORD.⁸⁷

2.8.3.6.3 Tobacco cessation

Tobacco use has been associated with an adverse effect on lower oesophageal sphincter function, however, the evidence from case-control studies to date does not support an improvement in GORD symptoms after cessation of tobacco use.^77,85,173 Tobacco cessation to improve GORD symptoms is not recommended but could be done relative to patient’ co-morbidity.⁸⁵