Long-term PPI use disrupts absorption of B12, calcium, iron, and magnesium, raising risks to bone, brain, and immune health and weakening nutrient balance.
Studies clearly suggest that psychosocial stress may have a significant relationship with reflux esophagitis and could play a potential role in symptom presentation and natural history. There is a close association between stress and reflux esophagitis, and a high likelihood that patients with refractory GERD may have comorbid psychosocial health problems. These stressors may include increased levels and frequency of esophageal acid exposure, inhibition of gastric acid emptying, or stress-induced hypersensitivity. A mindfulness-based intervention for anxiety symptom relief and quality of life in gastroesophageal reflux disease.
The protective role of melatonin on the gastric mucosa is due to the inhibition of gastric acid and pepsin secretion. Gastric acid and pepsin are two important invasive factors in the pathogenesis of gastric ulcers and are associated with stress-induced gastric mucosal lesions.
It has been observed that in animal models of chronic gastric fistula, melatonin reduced gastric acid and also increased plasma gastrin levels.
It is suggested that this inhibitory effect of melatonin is related to the central nervous system. Melatonin is also believed to control alkali secretion in the presence of acid in the lumen. Melatonin has been shown to protect the gastrointestinal mucosa by stimulating the production of mucosal HCO3- by inducing the release of intracellular Ca+2 in enterochromatic cells.
In the link ----1) Melatonin and mucosal protection and ulcer healing. ----2) Melatonin and Helicobacter pylori. ----3) Melatonin and stomach cancer. ----4) Melatonin and intestinal functions ----5) Melatonin’s effects on intestinal bacteria and the bacteria’s effects on the amount of melatonin. ----6) Melatonin and irritable bowel syndrome. ----7) Melatonin and inflammatory bowel disease. ----8) Melatonin and colorectal carcinoma. ----9) The role of melatonin in the liver. ----10) Melatonin and the pancreas. ----11) Melatonin and appetite.
Acute auditory stress has been shown to exacerbate heartburn symptoms in GERD patients by enhancing the perceptual response to intraesophageal acid exposure.
Various endogenous and exogenous stressors disrupt gastrointestinal physiological functions and promote inflammation, tissue damage, ulceration, gastrointestinal bleeding, gastroesophageal reflux disease (GERD), irritable bowel disease (IBD), and gastritis. Melatonin, on the other hand, plays important roles in both cholangiocytes and the gastrointestinal tract. The abundance of melatonin generated in the GI tract and its widely distributed receptors facilitate its protective effects in GI tissues. In most cases, disease progression in the gastrointestinal tract, particularly in the bile duct, is associated with suppression of the endogenous melatonin system. Increasing endogenous melatonin production appears to be a suitable strategy for slowing disease progression in these tissues.
Conventional pharmacological agents for the treatment of common gastrointestinal disorders (prevalence of 10–25%) can be associated with significant adverse effects in some patients. There is a rationale for developing alternative therapeutic strategies for these individuals. This article reviews the evidence for the use of supplemental melatonin, a substance with an excellent safety record and no significant adverse effects, in the management of gastroesophageal reflux disease, gastritis, irritable bowel syndrome, and ulcerative colitis.
PPIs may cause potentially harmful effects by several mechanisms, including endothelial dysfunction, hypomagnesemia, drug interactions, reduced absorption of selected nutrients, increased gastric microbiota and small intestine bacterial overgrowth, reduced immune response, tubular-interstitial inflammation, increased bone turnover, accumulation of amyloid in the brain.
There are a number of clinical studies that associate PPI use with an increased cardiovascular risk. In this article, we review the clinical evidence for adverse cardiovascular effects of PPIs, and we discuss possible biological mechanisms by which PPIs can impair cardiovascular health.
Among the 52,443 individuals who were taking a PPI and experienced an adverse event which was registered on the FDA database, 726 (1.38%) experienced MI. Of all the PPIs, esomeprazole had the largest proportion of users experiencing MI (1.81%). Compared to other PPIs, esomeprazole was associated with a significantly higher rate of MI (odds ratio [OR] =1.53, whereas lansoprazole was associated with a lower rate of MI (OR = 0.74).
Odds ratios (ORs), hazard ratios (HRs), and risk ratios (RRs) between PPI use and bone fracture incidence were pooled under the random effects model, and meta-analysis of standardized mean differences between PPI users and controls in cross-sectional values. that PPI use might increase fracture risk-
PPI use was independently associated with increased risk of first-time cardiovascular event, consistent with the evidence that PPIs adversely impact vascular function.
A new study establishes a disturbing link between taking those drugs and the rate of developing liver cancer.
In a shocking finding, individuals’ PPI use was associated with an 80% increased risk of liver cancer, compared with people who did not use PPIs.1
There have been other ominous findings about this drug category previously. Studies have shown that PPIs can reduce nutrient absorption, cause bacterial overgrowth, and are associated with increased risk of cardiovascular, kidney, and neurodegenerative brain diseases.
Long-term use of PPIs can lead to significant deficiencies of vitamins (B 12 and C) and minerals (iron, calcium and magnesium) that require gastric acid for absorption and bioavailability. Long-term use of PPIs by pregnant patients may pose a potential risk of birth defects. Long-term acid suppression by PPIs can also cause enteric, respiratory, and urinary tract infections. Hypochlorhydria from chronic PPI use can induce hypergastrinemia, which ultimately mediates gastric polyps, gastric carcinoids, and gastric cancer. The concomitant use of PPIs with antiplatelet agents such as clopidogrel may impose major adverse cardiac events on patients. This review has compiled comprehensive information on the adverse effects induced by long-term use of PPIs and their possible relationships.
This study is very comprehensive: Dietary and Lifestyle Factors Related to Gastroesophageal Reflux Disease: A Systematic Review
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055252/ (2021).-----
Studies clearly suggest that psychosocial stress may have a significant relationship with reflux esophagitis and could play a potential role in symptom presentation and natural history. There is a close association between stress and reflux esophagitis, and a high likelihood that patients with refractory GERD may have comorbid psychosocial health problems. These stressors may include increased levels and frequency of esophageal acid exposure, inhibition of gastric acid emptying, or stress-induced hypersensitivity. A mindfulness-based intervention for anxiety symptom relief and quality of life in gastroesophageal reflux disease.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3576549/ (2013).---
https://www.sciencedirect.com/science/article/abs/pii/S0016508507021713 (2008).---
https://gut.bmj.com/content/56/9/1191.short (2007)
https://mspsss.org.ua/index.php/journal/article/view/21 (2018).---
https://www.sciencedirect.com/science/article/pii/S2666149723000208 (2023).--
https://www.sciencedirect.com/science/article/pii/S2666149723000208 (2023).--
Various stressors Endogenous and exogenous factors disrupt gastrointestinal physiological functions and promote inflammation, tissue damage, ulceration, gastrointestinal bleeding, gastroesophageal reflux disease (GERD), irritable bowel disease (IBD), and gastritis.
http://www.melatonin-research.net/index.php/MR/article/view/120 (2021)
The protective role of melatonin on the gastric mucosa is due to the inhibition of gastric acid and pepsin secretion. Gastric acid and pepsin are two important invasive factors in the pathogenesis of gastric ulcers and are associated with stress-induced gastric mucosal lesions.
It has been observed that in animal models of chronic gastric fistula, melatonin reduced gastric acid and also increased plasma gastrin levels.
It is suggested that this inhibitory effect of melatonin is related to the central nervous system. Melatonin is also believed to control alkali secretion in the presence of acid in the lumen. Melatonin has been shown to protect the gastrointestinal mucosa by stimulating the production of mucosal HCO3- by inducing the release of intracellular Ca+2 in enterochromatic cells.
In the link ----1) Melatonin and mucosal protection and ulcer healing. ----2) Melatonin and Helicobacter pylori. ----3) Melatonin and stomach cancer. ----4) Melatonin and intestinal functions ----5) Melatonin’s effects on intestinal bacteria and the bacteria’s effects on the amount of melatonin. ----6) Melatonin and irritable bowel syndrome. ----7) Melatonin and inflammatory bowel disease. ----8) Melatonin and colorectal carcinoma. ----9) The role of melatonin in the liver. ----10) Melatonin and the pancreas. ----11) Melatonin and appetite.
https://www.mednews.care/wp-content/uploads/2024/02/therapeutic-applications-of-melatonin-in-disorders-related-to-the-gastrointestinal-tract-and-control-of-appetite.pdf (2024).-- Studies clearly suggest that psychosocial stress may have a significant relationship with reflux esophagitis and could play a potential role in the presentation of symptoms and natural history.
Acute auditory stress has been shown to exacerbate heartburn symptoms in GERD patients by enhancing the perceptual response to intraesophageal acid exposure.
https://www.sciencedirect.com/science/article/pii/S2666149723000208 (2023).--
https://www.sciencedirect.com/science/article/pii/S2666149723000208 (2023).--
Various endogenous and exogenous stressors disrupt gastrointestinal physiological functions and promote inflammation, tissue damage, ulceration, gastrointestinal bleeding, gastroesophageal reflux disease (GERD), irritable bowel disease (IBD), and gastritis. Melatonin, on the other hand, plays important roles in both cholangiocytes and the gastrointestinal tract. The abundance of melatonin generated in the GI tract and its widely distributed receptors facilitate its protective effects in GI tissues. In most cases, disease progression in the gastrointestinal tract, particularly in the bile duct, is associated with suppression of the endogenous melatonin system. Increasing endogenous melatonin production appears to be a suitable strategy for slowing disease progression in these tissues.
http://www.melatonin-research.net/index.php/MR/article/view/120 (2021)
Conventional pharmacological agents for the treatment of common gastrointestinal disorders (prevalence of 10–25%) can be associated with significant adverse effects in some patients. There is a rationale for developing alternative therapeutic strategies for these individuals. This article reviews the evidence for the use of supplemental melatonin, a substance with an excellent safety record and no significant adverse effects, in the management of gastroesophageal reflux disease, gastritis, irritable bowel syndrome, and ulcerative colitis.
https://www.magonlinelibrary.com/doi/abs/10.12968/gasn.2021.19.3.18 (2021)
PPIs may cause potentially harmful effects by several mechanisms, including endothelial dysfunction, hypomagnesemia, drug interactions, reduced absorption of selected nutrients, increased gastric microbiota and small intestine bacterial overgrowth, reduced immune response, tubular-interstitial inflammation, increased bone turnover, accumulation of amyloid in the brain.
https://www.ingentaconnect.com/contentone/ben/cdm/2018/00000019/00000002/art00010 (2018)
There are a number of clinical studies that associate PPI use with an increased cardiovascular risk. In this article, we review the clinical evidence for adverse cardiovascular effects of PPIs, and we discuss possible biological mechanisms by which PPIs can impair cardiovascular health.
https://link.springer.com/article/10.1007%2Fs40256-016-0160-9 (2016)
Among the 52,443 individuals who were taking a PPI and experienced an adverse event which was registered on the FDA database, 726 (1.38%) experienced MI. Of all the PPIs, esomeprazole had the largest proportion of users experiencing MI (1.81%). Compared to other PPIs, esomeprazole was associated with a significantly higher rate of MI (odds ratio [OR] =1.53, whereas lansoprazole was associated with a lower rate of MI (OR = 0.74).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6830015/ (2019)
Odds ratios (ORs), hazard ratios (HRs), and risk ratios (RRs) between PPI use and bone fracture incidence were pooled under the random effects model, and meta-analysis of standardized mean differences between PPI users and controls in cross-sectional values. that PPI use might increase fracture risk-
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6135649/ (2018)
PPI use was independently associated with increased risk of first-time cardiovascular event, consistent with the evidence that PPIs adversely impact vascular function.
https://www.sciencedirect.com/science/article/abs/pii/S0021915018313443 (2018)
A new study establishes a disturbing link between taking those drugs and the rate of developing liver cancer.
In a shocking finding, individuals’ PPI use was associated with an 80% increased risk of liver cancer, compared with people who did not use PPIs.1
There have been other ominous findings about this drug category previously. Studies have shown that PPIs can reduce nutrient absorption, cause bacterial overgrowth, and are associated with increased risk of cardiovascular, kidney, and neurodegenerative brain diseases.
https://www.urologyofva.net/articles/category/longevity/3215387/proton-pump-inhibitors-raise-risk-of-liver-cancer (2019)
Long-term use of PPIs can lead to significant deficiencies of vitamins (B 12 and C) and minerals (iron, calcium and magnesium) that require gastric acid for absorption and bioavailability. Long-term use of PPIs by pregnant patients may pose a potential risk of birth defects. Long-term acid suppression by PPIs can also cause enteric, respiratory, and urinary tract infections. Hypochlorhydria from chronic PPI use can induce hypergastrinemia, which ultimately mediates gastric polyps, gastric carcinoids, and gastric cancer. The concomitant use of PPIs with antiplatelet agents such as clopidogrel may impose major adverse cardiac events on patients. This review has compiled comprehensive information on the adverse effects induced by long-term use of PPIs and their possible relationships.
https://www.sciencedirect.com/science/article/abs/pii/S004059572030127X (2020)