J C MEEROFF, MD, Ph.D and S. MEEROFF
South Florida Institute of Integrative Medicine, USA
“There are
no closed questions, but men closed on the questions” Santiago Ramon y Cajal
“Unfortunately,
only a small number of patients with peptic ulcer are financially able to make
a pet of an ulcer.” William J Mayo
“The
20th-century ulcer epidemic was a sign of good health in American people - good
diet, strong acidity and healthy immune response make ulcers more likely.
That's why businessmen eating giant T-bone steaks were prone to ulcers.” Barry Marshall
“If you
spend your life competing with businessmen, what do you have? A bank account
and ulcers” Marilyn Monroe
“It’s
not that I’m so smart, it’s just that I stay with problems longer.” Albert
Einstein
“Not every
problem can be solved by science alone.”
JC Meeroff
“Often we
look so long at the closed door that we don’t see the one that has been open
for us.” Hellen Keller
INTRODUCTION
It was established long time ago that “within
the field of gastroenterology, the majority of symptoms cannot be explained by
structural abnormalities detected on routine investigations” . The American
College of Gastroenterology have estimated that in the US “burning pain from
acid indigestion” affects an estimated 60 million people at least once a month
and 15 million people daily. Therefore, there is no doubt that “acid
indigestion” constitutes a major clinical problem.
The stomach is the organ responsible for the
initial digestion
of food and for the extermination
of any potential pathogenic microorganisms that may have been ingested.
That is why the stomach secretes hydrochloric acid (HCl), pepsin and mucus. The
pH of normal gastric juice is very low, it varies between 1.5-3.5, indicating a
high concentration of hydrogen ions that is crucial to kill pathogenic germs . On
the negative side too much acid can irritate, hurt and destroy the tissues it comes
in contact with particularly those who are not intended to withstand a very low pH.
BASIC PHYSIOLOGY OF GASTRIC ACID
SECRETION
HCl is produced by the parietal cells of the mucosa of the stomach.
The process begins with the combination of water (H2O) and carbon dioxide (CO2)
to produce carbonic acid (H2CO3), a chemical reaction catalyzed by the
enzyme carbonic anhydrase. Carbonic acid then spontaneously dissociates
into a hydrogen ion (H+) and a bicarbonate ion (HCO3–).
The formed H+ is transported into the stomach lumen via the H+/
K+ ATPase ion pump or Proton Pump (PP+). This pump uses ATP as an energy
source to exchange potassium ions (K+) with H+ ions.
The HCO3– is transported out of the cell into the blood via a
transporter protein called anion exchanger 2 which trades HCO3– for Cl–. The chloride ion is then transported into
the stomach lumen via a chloride channel mechanism.
This results in both Cl – and H+ being present in gastric juice. Their
opposing charges make them to associate with each other forming hydrochloric
acid (HCl).
At rest, the number of active PP+ present
within the parietal cell membrane is minimal. The pump surplus is sequestered
within tubulovesicles inside the parietal cells. Upon stimulation the
vesicles fuse with the cell membrane which leads to the increased insertion of PP+
into the membrane, leading to the intensification of acid production.
The stomach protects itself from
being digested by its own enzymes, and/or burnt by the corrosive effects of HCl
by secreting sticky and neutralizing mucus that covers
the stomach walls. If this layer becomes damaged the result is the
formation of painful and unpleasant stomach erosions and/ or ulcers.
Gastric acid
secretion (GAS) is regulated by different mechanisms that overlap among each
other. For didactical purposes it is possible to separate them into three
different phases
ü Cephalic
ü Gastric
ü Intestinal
The cephalic
phase is mediated via acetylcholine (Ach), which is released from the vagus nerve. The parasympathetic, cholinergic
activity of the vagus nerve is activated upon seeing or chewing food, leading
to direct stimulation of the parietal cells. Neurogenic signals that initiate
the cephalic phase of gastric secretion originate from the cerebral cortex and
the appetite centers of the amygdala and the hypothalamus. They are transmitted
through the dorsal motor nuclei of the vagus, and then via the vagus nerve to
the stomach. This cholinergic activation is also produced during the gastric
phase of digestion when intrinsic nerves detect distension of the stomach,
stimulating the production of ACh by the vagus nerve.
The gastric phase
involves the hormone gastrin which is secreted by the enteroendocrine
G cells of the pyloric glands. G cells are activated by the vagus nerve, by gastrin
related peptides and by food peptides produced via protein digestion.
Activation of the G cells leads to the production of gastrin which is discharged
into the blood to travel until it reaches the parietal cells. Gastrin binds to
CCK receptors on the parietal cells which also elevates calcium levels causing
increased vesicular fusion. Small peptides also buffer the stomach acid, so the
pH does not fall too low. As digestion continues and these peptides clear out from
the stomach, the pH drops lower and lower. However, below pH of 2, stomach acid
inhibits the parietal cells and G cells via the production of somatostatin from the D cells. This
is a negative feedback loop that shuts down the gastric phase as the need for
pepsin and HCl declines.
Finally,
enterochromaffin like cells in the stomach secrete histamine which binds
to H2 receptors on the parietal cells. These cells release histamine
in response to the presence of gastrin and ACh. This also produce an increased PP
fusion via the secondary messenger cAMP as
opposed to calcium in the other mechanisms.
The intestinal phase occurs
when food that has been broken down to chyme, passes
into the duodenum, triggering the enterogastric reflex. This reflex can be
also stimulated by distention of the small bowel. If there is excess acid in
the upper intestine, the presence of protein breakdown products as well as
excess irritation to the mucosa sent inhibitory signals to the stomach via the
enteric nervous system, as well as signals to the medulla reducing vagal stimulation
of the stomach. The enterogastric reflex, is important to slow down gastric
emptying when the intestines are already filled.
The
presence of chyme within the duodenum also stimulates entero-endocrine
cells to release cholecystokinin and secretin, both of
which play important roles in completing digestion, but also inhibit gastric
acid secretion. Secretin is released by the S cells of the duodenum when
there is excessive acid production in the stomach.
Other
hormones including glucose dependent insulinotropic peptide (GIP) and
vasoactive intestinal polypeptide also work to decrease acid production in the
stomach.
The 3 main chemicals
involved in stimulating gastric acid secretion are histamine, acetylcholine (Ach) and gastrin. The mechanisms by which
each of those 3 stimulants turn-on gastric acid secretion are complex but we
can simplify their actions as follows:
Histamine is
released by Enterochromaffin-Like cells in the stomach
Histamine's effect on the parietal cell is to activate the
enzyme adenylate
cyclase, leading to the elevation of intracellular cyclic AMP
concentrations and activation of protein kinase A (PKA). One effect of PKA
activation is phosphorylation of cytoskeletal proteins involved in transport of
the PP+ from cytoplasm to plasma membrane.
Ach and gastrin may work by rising intracellular calcium that
is necessary for the PP+ to function
Fig 1
Summary of gastric acid stimulation by Acetylcholine, histamine and gastrin
WHAT TRIGGERS GASTRIC HCL HYPERSECRETION
Currently
acid indigestion and gastric hypersecretion are still medical mysteries. The
investigation of gastric hypersecretory states continues to be a dark area of clinical gastroenterology. Once
it was discovered by Barry J. Marshall and Robin Warren, that a bacteria called
Helicobacter Pylori (HP) is responsible for a significant proportion of
gastroduodenal ulcers, the medical community decided dogmatically that all
ulcers were produced by such infection and they literarily abandoned most of
the clinical methods for the diagnosis of gastric problems.. Currently gastric
analysis, once a very common technique used to measure the amount of acid
produced by the stomach, is very seldom performed in clinical practice.
Therefore, we rarely know if a patient secretes too much gastric HCl or not. We
rely just on symptoms referred by the patient which constitute a very erratic source
of information
Epigastric
pain (brûlure epigastrique in French or ardor
de estómago in Castilian Spanish), peptic ulcer disease (PUD), gastroesophageal
reflux (GER) and other forms of pyrosis are common clinical features yet poorly understood symptoms. They can be secondary to hypersecretion of HCl
as well as to hyposecretion of HCl, to inflammation, to deficient secretion of
mucus and/or to bile reflux.
Gastric acid secretion is a complex process
controlled by 3 interrelated pathway: cholinergic, histaminergic and
peptidinergic.s. Disorders in the pathways can lead to gastric acid
hypersecretion. Currently it is possible to tentatively classify HCl hypersecretory
states as follows:
1. HCl hypersecretion with hypergastrinemia
1.1 Zollinger-Ellison syndrome (ZES)
Relatively rare but many times malignant neuroendocrine tumors secreting
excess of gastrin.,
1.2 Antral G cell hyperplasia (Ps-ZES)
A very rare benign G cell hyperplasia producing large volumes of gastric
acid.
1.3 Gastric dysmotility states
Vague syndromes causing gastroparesis or simply delayed gastric emptying
and gastric distension. Some are associated with alterations in the metabolism
of CHOs (diabetes) while others are linked to infections with viruses and/or
bacteria.
1.4 Gastric outlet functional and/or
mechanical obstructions
Any situation causing difficulties for rapid gastric emptying via a well
functioning pylorus will produce gastric distension that stimulated the release
of gastrin
1.5 Chronic renal failure
During renal failure there is a decrease catabolism of gastrin as well as
other, still poorly understood, mechanisms producing small peptides that stimulate
the parietal cells of the stomach.
1.6 Helicobacter
Pylori (HP) infection
This is the
most relevant of the hypersecretory states with hypergastrinemia since a substantial
number of the so called “peptic ulcers” are caused by an infection with HP. Nevertheless,
a large proportion of HP gastritis are confined to the antrum and unaccompanied
by enhanced release of gastrin therefore not having hypersecretion of gasric
acid.
1.7 Consuming non-distillated
ETOH beverages
ETOH beverages produced by fermentation
but not further distilled, increase the production of GAS via stimulation of
the secretion of gastrin. However, it was proved that pure ETOH at a concentration >10% inhibits
GAS and beverages with low ETOH concentrations (beer) do not alter GAS. The
stimulatory non-alcoholic ingredients in non-distilled alcoholic beverages are
most likely produced during the process of fermentation of carbohydrates and can
be removed during the following distillation.
2. HCl hypersecretion with normal gastrinemia
2.1 Systemic
mastocytosis with hyperhistaminemia
Histamine is
synthesized by the decarboxylation of the amino acid L-histidine by a single
enzyme, histidine decarboxylase (HDC). The presence of HDC has been reported in
many human cell types, including mast cells, basophils, gastric parietal cells,
and others. There is also evidence suggesting that this enzyme is present in
vascular and lymphatic endothelial cells, pericytes (Rouget cells), smooth
muscle cells, and platelets. Although histamine has a short half-life in
vivo, due to rapid enzymatic degradation by either diamine oxidase (DAO) or by
histamine-N-methyltransferase (H-NMT), it can be stored in cytoplasmic granules
within mast cells and basophils after it has been synthesized, to be subsequently
released by degranulation. Studies in humans and in animal models have provided
strong evidence that histamine is an important mediator of post-exercise
hypotension and sustained post-exercise vasodilation as well as a stimulant of
gastric HCl secretion.
2.2 Food
induced HCl hypersecretion
This is perhaps
the most frequent form of HCl hypersecretion. The mechanism by which foods
stimulates gastric secretion is still not fully understood but it is probably
secondary to the distention of the antrum and mediated by the release of Ach. The
most common stimulants include high fat dairy products, high fat meats, ETOH,
coffee, pepper mint, high fiber foods, spicy foods, onions, tomatoes, milk
chocolate, carbonated sodas and citrus beverages.
2.3 Idiopathic
gastric acid hypersecretion
When we
don’t have any clue of what is causing HCl hypersecretion we call it Idiopathic
gastric acid hypersecretion. Hopefully future research will eliminate this
category.
3. Stress induced HCl hypersecretion via over stimulation of the
parasympathetic nervous system that increases the release of Ach
That “nervous
stress” caused ulcers was an empiric concept well accepted in the 20th
century. Unfortunately, nobody could prove that “nervous stress” (a dubious
concept, not well defined nor scientifically understood) produce increased
secretion of gastric HCl.
Let’s review
the evidence. When an individual is exposed to excessive imposed demands (EID),
that can be psychological, chemical and/or physical, the body responds (stage 1
of stress or alarm reaction) with an increase activity of the sympathetic
nervous system (adrenergic response) involving the release of nitric oxide in
the vicinity of gastric parietal cells which reduce gastric acid secretion.
Once the EIDs are neutralized (stage 2 of stress or resistance), the body
initiates the recovery of balance by increasing the activity of the
parasympathetic nervous system (cholinergic response) that in fact increases GAS,
leading to GI symptoms such as gastric hyperacidity, gastric distension, and
gastroesophageal reflux (GER). This is the reason why the so-called “stress
ulcers” don’t appear during the alarm stage of stress but instead at some point
in the resistance stage or even in the exhaustion stage after the EIDs disappeared
and the system is regaining balance. If we aim to find hypersecretion of HCl we
must test not during the alarm period but while balance is being restored.
(Meeroff JC & Meeroff M, Basal gastric acid output during the different
phases of stress. Unpublished data).
Furthermore, this may explain why patients who suffered a stressful condition
must be protected from gastric HCl hypersecretion well after the event was
terminated.
4. Combined mechanisms of stimulation of
gastric HCl secretion
Bitter tasting
compounds including caffeine present in coffee and tea beverages increase HCl
secretion through the release of Ach, gastrin and/or histamine from activation
of taste receptors, enteroendocrine cells and/or by modulating acid production
in GAS-producing parietal cells
OBESITY AND INCREASED RISK OF UPPER
GI MUCOSAL CHANGES
Obesity is associated with increased chronic systemic inflammation,
changes in the gut microbiome composition, disruption of the normal gastric
mucosal epithelium barrier, increased risk for gastric peptic ulcer formation,
GE reflux and gastric cancer. There is preliminary, fractionated but
inconclusive data indicating that obese patients produce more gastric HCl than
non-obese ones. Furthermore, since obese people eat more food it is suspected
that they produce more HCl via distention of the antrum leading to a
cholinergic effect on parietal cells.
CLINICAL EFFECTS OF GASTRIC ACID
HYPERSECRETION
Disproportionate
amounts of HCl in the upper GI tract lumen can cause serious medical problems
including:
ü Gastroduodenal mucosal damage = ulcers,
erosions.
ü Gastroesophageal reflux leading to esophageal
dysfunction = GER, GERD, Barrett’s esophagus, Non-erosive reflux disease (NERD)
ü Disturbance of the digestive process
in the upper GI tract = diarrhea, malabsorption, anemia, osteoporosis
ü Modification of the intestinal
microbiota: diarrhea, immune problems
HOW TO CONTROL GASTRIC ACID
HYPERSECRETION
1. Controlling the production of HCl
Anticholinergics or antimuscarinics
Anticholinergic
drugs, recommended for a variety of clinical conditions, are amongst the most
frequently used prescription drugs in the world. They specifically block
muscarinic receptors for ACh. Antimuscarinic gastric agents such as belladona
tincture, atropine, homatropine, hyoscine, hyoscyamine, propantheline, dicyclomine
and others have strong antispasmodic and antisecretory actions in the stomach. Anticholinergics
act by binding and blocking the Ach receptors of the parietal cells.
Antimuscarinic drugs have been used to treat gastric acid problems since the
mid 1900’s and are very effective but they have some negative side effects of
concern, therefore we must use them with caution, particularly in the elderly
The most common anticholinergic adverse
effects include the following:
ü Visual/auditory/sensory hallucinations
ü Tremors/myoclonic jerking
ü Memory and cognitive impairment, altered mental status,
dementia
ü Tachycardia , dry eyes,
ü Difficulty adjusting visual focus (lens accommodation)
ü Sensitivity to bright light (dilated pupils)
ü Decreased sweating/dry skin
ü Difficulty starting urination/impaired bladder
emptying
ü Urinary retention/overflow incontinence
H2 blockers
Gastric
parietal cells possess histamine H2 receptors that allow histamine to stimulate
the secretion of HCl. H2 antagonists or H2 blockers, are drugs that
block the action of histamine at the histamine
H2 receptors of
the parietal cells in the stomach. This competitive antagonist blockage decreases the
production of stomach acid.
H2 antagonists suppress
the normal secretion of acid by parietal cells and also the meal-stimulated
secretion of acid. They accomplish the antisecretory action by switching off
the parietal cell response to histamine, gastrin and Ach.
H2 blockers include agents
such as cimetidine, ranitidine, famotidine, and roxatidine. They have different
chemical structures but basically they produce the same effect on the parietal
cell that is binding to the H2 receptor to avoid histamine stimulating the
cell. Cimetidine is an imidazole derivative; ranitidine belongs to the
basically substituted furans, famotidine is a member of the guanidinothiazole
group; and roxatidine belongs to the aminoalkylphenoxy series.
The H2 receptor antagonists are
reversible competitive blockers of histamine at the H2 receptors, particularly
those in the gastric parietal cells, where they inhibit acid secretion. They
are highly selective, do not affect the H1 receptors, and are not
anticholinergic agents. However they show some prokinetic activity as well. Tobacco
interferes with H2 blockers ability to block the gastric receptors and ETOH
catabolism is diminished producing high levels of ETOH in the blood.
H2 blockers
are very effective for reducing gastric HCL secretion but they have shown some potentially
serious long term side effect for which reason they are currently not
recommended to treat acid indigestion problems. They major side effect include
ü Cardiac arrhythmias mostly bradycardia
ü Gynecomastia, Impotence, sterility
ü Imbalance in the normal gut microflora with small
intestine bacterial overgrowth (SIBO)
ü Calcium malabsorption and osteoporosis
ü Confusion, Alzheimer’s disease, dementia
ü Cancer because they may contain unacceptable levels of
N-nitrosodimethylamine (NDMA) that is hepatotoxic and a known carcinogen
Proton Pump Inhibitors (PPIs)
PPIs act by irreversibly blocking
the hydrogen/potassium adenosine
triphosphatase enzyme system or PP+ of the gastric parietal cells. The PP+ is the terminal stage in gastric acid
secretion chain, being directly responsible for secreting H+ ions into the
gastric lumen, making it an ideal target for inhibiting acid secretion. PPIs
are given in an inactive form, which is neutrally charged (lipophilic) and readily crosses cell membranes into intracellular compartments (like the parietal cell canaliculus) with acidic
environments. In an acid environment, the inactive drug is protonated and
rearranges into its active form. The active form will covalently and
irreversibly bind to the gastric proton pump, deactivating it.
All PPIs are
derivatives of the 2-pyridylmethylsulfinylbenzimidazole basic structural
framework and differ only in the nature of substituents placed on the pyridine
and benzimidazole rings. Currently the following PPI products are available
in the market in the US: omeprazole, esomeprazole, lansoprazole, pantoprazole,
and rabeprazole.
PPIs are
effective for reducing gastric HCl secretion, probably more than the H2
blockers but they have a short plasma half-life, a short duration of
antisecretory effect due to the activation of new Proton pumps and poor
nocturnal control of GAS. They also have shown some potentially dangerous long
term side effect including:
ü Creating the environment for C. Difficile infections, SIBO,
etc
ü Deterioration of cognitive abilities leading to
dementia
ü Producing interstitial nephritis leading to chronic
kidney disease
ü Reduce absorption of magnesium and calcium leading to
osteopenia
ü Increased risk for nephrolithiasis
ü Multiple drug important interactions
PPIs
interact with many therapeutically known agents such as:
ü Clarithromycin (increased absorption)
ü Digoxin (increased absorption)
ü Ketoconazole (decreased tablet dissolution leading to
decreased absorption)
ü Indinavir (decreased tablet dissolution leading to
decreased absorption)
ü Salicylates (increased enteric-coated tablet dissolution
leading to an increase in gastric side effects)
ü Theophylline (increased absorption from sustained
release formulations)
ü Vitamin B12 (decreased absorption)
ü Antiplatelet agents (decrease activity)
In summary:
PPIs are very effective to control HCl hyper secretory conditions, but their
use must be limited in time to prevent serious complications.
Potassium-Competitive Acid Blockers (P-CABs)
The
need for new acid suppressing drugs with improved pharmacology and superior
antisecretory effects has been clear for the last decades.
P-CABs are a new class of PP+ blockers. Opposite to the
classic PPIs, P-CABs result in a very fast, competitive, reversible inhibition
of proton pumps. They produce a fast, very effective and reversible blockade of
acid secretion induced by this class of drugs. The prazans are weak bases, and
the protonated form of these drugs inhibits the H+ K+ ATPase enzyme.
P-CABs are a group of drugs developed in the 1980s. and currently
one of them, Vonoprazan, is in the market in Japan . P-CABs do not require
proton pump activation to achieve their action; further, they have rapid action
onset and reduce acid secretion due to a steady rise in their plasma
concentration. Vonoprazan is well tolerated and produced a rapid, profound and
sustained suppression of gastric acid secretion.
It is speculated that clinically P-CABs will have similar or
better efficacy than PPIs with similar or lower side effects. Other Prazans ready
to be on the market in the far east include Tegoprazan and Revaprazan.
Opposing
hormones : Somatostatin and, cholecystokinin
(CCK),
Both
somatostatin and octreotide an octapeptide with somatostatin pharmacological effects reduce Gas
significantly but they are not used to treat GAS syndromes. Octreotide is often
given as an infusion for management of acute hemorrhage from esophageal varices in
liver cirrhosis on
the basis that it reduces portal venous pressure, though
current evidence suggests that this effect is transient and does not improve
survival.
Cholecystokinin
(CCK) and Sinclide an octapeptide with CCK like effects are also potent
inhibitor of GAS. They are used mostly to aid radiological and /or chemical studies of the GI tract
Reducing the
availability of ACh in the circulation by physical exercise
During intense
exercise the levels of ACh drop significantly. This is due to a decrease
in plasma choline levels. Choline or Vitamin B4 is the precursor of Ach and it
is used during exercise particularly to assist in the catabolization of lipids,
therefore decreasing the production of Ach.
Exercise
also generates an excess of CO2 (CO2 is necessary to produce HCL by the
parietal cells), but during exercise free CO2 is rapidly removed from the body
by the lungs, therefore decreasing the availability of CO2 to the parietal
cells of the stomach. Well documented research data supports the hypothesis that
GAS decreases significantly immediately after exercise
Reducing HCl
secretion by inhibiting vagal over activity
Acupressure
and acupuncture significantly reduce GAS. The mechanism involved are still not
clear, but it will probably be via inhibition of vagal stimulation. Both
procedures are simple, safe and devoiced of side effects.
2. Neutralizing HCl in the lumen of the
GI tract
Antacids
Inorganic antacids
neutralize HCL secreted into the lumen of the stomach. Sodium bicarbonate,
magnesium, aluminum and calcium salts are commonly used to control
hyperacidity. They are very effective and not expensive, but they have some
important long-term side effects to take into consideration. Those negative
side effects are diarrhea, constipation, SIBO, osteoporosis, kidney diseases
and a probability of increase incidence of Alzheimer's disease and
dementia.
Alkalinizing foods
Milk and other dairy
products were the principal mode of treatment of gastroduodenal ulcers during
the early 1900’s, later on it was found that milk does not reduce GAS, but more
recently it was also proved that milk can neutralize GAS and protect the
mucosa. Currently the accepted criteria is that if the patient tolerates dairy
products well, they can use them to reduce pyrosis and/or heal ulcers
3. Protecting the mucosa against acid damage
Prostaglandins
Prostaglandins (PG) appear
to inhibit gastric acid secretion by acting directly on the parietal
cells and making these unresponsive to most stimulants. PGs also increase
gastric mucosa blood flow and improve gastric mucus secretion. Prostaglandins
are rarely used to treat GAS syndromes. They are expensive and can produce
negative effects including tachyarrhytmias, seizures, anemia, respiratory
distress etc.
Sucralfate
Sucralfate is a complex of aluminium hydroxide and sucrose octasulfate. It dissociates in the acid environment of the stomach to its anionic form, which binds to the gastric mucosa particularly if it is eroded. This creates a protective barrier to pepsin and bile and inhibits the diffusion of gastric acid. Sucralfate is minimally absorbed but may produce undesirable side effects such as constipation and flatulence.
Bismuth
Bismuth, particularly
when used as bismuth subsalicylate (Pepto Bismol NR, Roter, NR), acts as an antimicrobial
bacteriostatic agent suppressing HPylori bacteria but not eliminating it completely
Bismuth may have also cytorotective capabilities
but this is still not completely proven.
Bismuth products are poorly
absorbed from the lumen of the GI track and have relatively very minor side
effects particularly darkening of the stools and/or tongue. These effects are harmless and will disappear when stopping the
medication.
Vitamin C derivatives
Vitamin C and derivatives
such as sodium oxyferriscorbone have antioxidant and healing properties and are
still used in Europe to treat gastroduodenal ulcers with success. They are inexpensive
and safe with little or no side effects, but their popularity has decreased
after the introduction of PPIs.
Turmeric curcumin
Turmeric is a South Asian spice used in many Indian dishes. It’s easily recognizable by its rich yellow color. It improves blood vessel function and reduce inflammation.The active part of the plant is curcumin’s which anti-ulcer potential has recently been studied in animals. It appears to have immense therapeutic potential, especially in preventing damage caused by H. pylori infections. It may also help increase mucus secretion, effectively protecting the stomach’s lining against irritants. Curcumin has practically no side effects and it is relatively inexpensive.
Zinc-hyaluronidase
Zinc-hyaluronidase
is among the long list of potentially cytoprotective agents used in Europa and
Asia to aid healing gastric ulcers, particularly those of trophic types (poor
vascular circulation, decreased defensive mechanisms). Zinc-hyaluronidase is
not in use in the US to treat PUD.
Honey
Honey is a popular,
natural sweetener consumed extensively across the world. Honey has proven antimicrobial
effects against H. pylori. Honey is also
use to speed healing of skin ulcers, burn and wounds. It is Inexpensive and
with relatively few negative side effects being the most noticeable one its
conversion into alcohols by fermentation when there is an overgrowth of
bacteria in the bowel. It is used to treat peptic ulcers in South America and in
the Far East more than in the US.
Quercetin, alpha-tocopherol
and other flavonoids
Plant flavonoids are
antioxidants found in many fruits, vegetables, leaves, seeds, grains particularly
in red onions among others. Antioxidants work to protect the cells
from free radicals. Free radicals are unstable molecules in the body that can increase the risk of chronic inflammation, disease and quick
aging. Plant flavonoids
improve the efficiency of the cellular mechanisms producing neutralizing agents
such as mucus and bicarbonate that are essential to neutralize excesses of HCl.
4. Improving the velocity and quality of gastric emptying using prokinetic agents
Dopaminergic agents such as metoclopramide and domperidone, cholinergic agonist such as bethanecol , act by accelerating the rate of gastric emptying from the stomach. Again, we are dealing with effective agents buy they may produce important undesirable side effects
CONCLUSIONS
PUD, NUD,
GER, GERD, simple pyrosis and other acid related disorders of the upper GI
tract are very common clinical conditions. Despite the fact that we still have
many grey areas to elucidate, especially those concerning with pathophysiologic
mechanisms, we have a vast arsenal of therapeutic agents to control HCl
hypersecretion. We recommend using a mixed approach, that is a combination of
different agents, to reduce and neutralize excessive acidity in the stomach and
to avoid as much as possible using medicines for extended periods of time
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