#Crohn's disease #saccharin #sucralose

1.14: web.med/crohn's disease:
. Crohn's disease, also known as regional enteritis,
is a type of inflammatory bowel disease (IBD);
which can increase the risk of cancer.
. the cause is officially unknown; but,
lifestyle choices that raise risk include
# saccharin or sucralose
# oral contraceptives,
# smoking or 2nd-hand smoke
# diets that provoke yeast or fungal overgrowth
(high in sugar or refined carb's;
or low in fiber that feed bacteria
that compete with yeasts)
# aluminum pollution in urban areas.
# low vitamin D
# nonsteroidal anti-inflammatory drugs
# prior use of antibiotics
(often killing the good germs results in
the growth of bad germs after antibiotics are discontinued;
IBD may be the immune system's response to a certain germ;
some are cured with a fecal transplant(good germs);
some go into remission on antibiotics.
. the GAPS diet might also work as an antibiotic:
it is a high-fat low-prebiotic diet that removes bad germs
followed by a fermented diet that adds good germs).
. being left-handed, you might be more inclined
to choose a lifestyle that increases risk.

def regional enteritis:
(aka Crohn disease; distal, regional, or terminal ileitis;
aka granulomatous or chronic cicatrizing enteritis).
A chronic enteritis involving the terminal ileum
[the final section of the small intestine]
and less frequently other parts of the gastrointestinal tract;
characterized by patchy deep ulcers that may cause fistulas
[holes in intestine leading to other organs]
and narrowing and thickening of the bowel by
fibrosis [scarring] and lymphocytic infiltration
[being filled with immune system cells]
with noncaseating tuberculoid granulomas
that also may be found in regional lymph nodes;
[Granuloma is a collection of immune cells
attempting to wall off what seems foreign.]
symptoms include fever, diarrhea, cramping abdominal pain,
and weight loss.

3.6: increased risk cancer:
. if you have chronic inflammation of the colon,
you are at a higher risk for developing CRC [colorectal cancer]
than the general population (unless your inflammation
is limited to the very bottom of the rectum).
If your Crohn's disease is limited to the small intestine,
you are at a slightly increased risk for cancer
in the areas that are involved.
Even if your disease is in remission, you remain at risk.
Two of the main factors associated with increased cancer risk
are disease duration and the extent of the colon involved.
The risk for CRC doesn't start increasing until 8 to 10 years
after you develop Crohn's disease or ulcerative colitis.
Finally, a rare complication of IBD is
primary sclerosing cholangitis (PSC), which causes
inflammation of the ducts that drain the liver.
If you have either PSC or a family history of CRC,
you may have a higher risk of developing CRC
before the 8- to-10-year period.

crohns.net`risk factors:
-- seems to be a copy of work by
Kathleen Head, ND, and Julie Jurenka, MT(ASCP)
Risk factors for Crohn's Disease include smoking,
use of oral contraceptives,
nonsteroidal anti-inflammatory drugs (NSAIDs),
and antibiotics [includes the artificial sweeteners,
saccharin and sucralose];
Crohns disease is more prevalent in developed countries
and is more common in white-collar workers
and individuals with indoor, sedentary occupations.
[more prone to use low-calorie artificial sweeteners]
Crohn's Disease patients reported more frequent use of
antibiotics in childhood and more frequent
upper respiratory infections.
Other factors that appeared to increase disease risk
were history of eczema, appendectomy in adulthood,
and consumption of a low fiber diet.
[that has an antibacterial pro-yeast effect]
Another study demonstrated
a higher frequency of childhood infections,
specifically pharyngitis,
as well as more frequent use of antibiotics
for otitis media and pharyngitis.
Women taking oral contraceptives
have twice the risk of developing Crohns Disease.
. contraceptives compound the risk of thromboembolic events,
which is already high due to
hypercoagulation characteristic of Crohn's Disease.
lefthanded individuals have twice the risk.

MMR vaccine does not increase the risk:
-- 3.6: vaccines are often suspected in autoimmune disorders;
eg, Linked to Aluminum In Vaccines.
. there is some evidence that Crohn's Disease
is partially an autoimmune disorder.

greenmedinfo.com`data base:

A combination of lactobacillus reuteri and lactobacillus rhamnosus
reduces inflammation in patients with Crohn's disease
or ulcerative colitis.
Clin Exp Immunol. 2007

An exclusion diet and nutraceutical therapy
[Boswellia, Colostrum, Curcumin, Fish extract,
Lactobacillus rhamnosus GG]
has significant therapeutic effects in juvenile Crohn's disease.
J Am Coll Nutr. 2009

Mastic gum has bactericidal activity on
H. pylori in patients suffering from infection.
J Med Food. 2006;

Mastic gum has significant therapeutic value in patients with
mildly to moderately active Crohns disease.
World J Gastroenterol. 2007

Tripterygium wilfordii Hook F was well tolerated
and prolonged remission in patients with Crohn's disease.
Am J Med Sci. 2015

Wormwood contributes to significant improvement
in treatment outcome for Crohn's disease.
Phytomedicine. 2007

Administration of fermented milk was effective in the
prevention of the intestinal damage associated to
inflammatory bowel disease in a murine model.
Curr Pharm Biotechnol. 2015

[ Elemental diets
aim to remove whole proteins and replace them with amino acids.
Certain medical conditions such as Crohn’s disease
are associated with allergic reactions to whole proteins.]

Dig Dis Sci. 1997:
Amelioration of chronic inflammation by ingestion of
elemental diet in a rat model of granulomatous enteritis.
The beneficial effect of elemental diet (ED)
in the treatment of Crohn's disease is reported,
although the exact mechanism for this remains to be elucidated.
In this study the effects of ED on intestinal inflammation
were investigated in a rat model of granulomatous enteritis.
Immunohistochemical study and immunocytochemical analysis of the cell suspension
from Peyer's patches showed accumulation of macrophages
and an increase in interleukin-2 receptor (IL-2R)-positive T cells
after [injection with something that causes bowel disease].
Chemiluminescence (ChL) activity
and nitrite and nitrate (NOx) levels
in the mesenteric venous blood
as well as Ca(2+)-independent (inducible)
nitric oxide synthase (NOS) activity in Peyer's patches
were increased.
In rats fed with ED, both macroscopic and histologic damage scores
were significantly decreased as compared with
those in rats fed with the control diet.
ED inhibited the increase in the numbers of macrophages
and IL-2R-positive T cells in Peyer's patches.
Increased ChL activity, NOx levels,
and Ca(2+)-independent NOS activity
were also reduced significantly by feeding with ED.
These data suggest that ED reduces progression of
PG-PS-induced chronic intestinal inflammation
by modulating activation of T cells, production of nitric oxide,
and generation of oxygen free radicals

Boswellia's immunomodulatory properties
may make it ideal for the treatment of
autoimmune and inflammatory diseases.
Phytomedicine. 2010
[ downregulation of Interleukin-1 alpha, Interleukin-2, -4, -6;
Leukotriene Antagonists
NF-kappaB Inhibitor
Tumor Necrosis Factor (TNF) Alpha Inhibitor ]

Curcumin may be effective against oxidative bowel damages
induced in IBD by imbalanced gut immune response.
Int Immunopharmacol. 2012
[Tumor Necrosis Factor (TNF) Alpha Inhibitor]

What made Canada become a country with
the highest incidence of inflammatory bowel disease:
could sucralose be the culprit?
Can J Gastroenterol. 2011

Ann N Y Acad Sci. 2007:
Aluminum is a potential environmental factor for
Crohn's disease induction: extended hypothesis.
Aluminum (Al) is a common environmental compound
with immune-adjuvant activity
and granulomatous inflammation inducer.
Al exposure is ubiquitous in Western culture:
in food, pharmaceuticals, air, and water pollution.
Crohn's disease (CD) is a chronic inflammation
in genetically susceptible individuals
and is influenced by yet unidentified environmental factors.
It is hypothesized, in the present review,
that Al is a potential factor for induction or maintaining
the inflammation in CD. Epidemiologically,
CD incidence is higher in urban areas,
where microparticle pollution is prevalent.
Al immune activities share many characteristics with
the immune pathology of CD:
increased antigen presentation and APCs activation,
many luminal bacterial or dietary compounds
can be adsorbed to the metal and induce Th1 profile activity,
promotion of humoral and cellular immune responses,
proinflammatory, apoptotic, oxidative activity,
and stress-related molecule expression enhancement,
affecting intestinal bacterial
composition and virulence, granuloma formation,
colitis induction in an animal model of CD,
and terminal ileum uptake. The Al-bacterial interaction,
the microparticles homing the intestine together
with the extensive immune activity,
put Al as a potential environmental candidate for
CD induction and maintenance.

Eur J Gastroenterol Hepatol. 1998:
Modern life' in the epidemiology of inflammatory bowel disease:
a case-control study with special emphasis on nutritional factors.
A positive association between Crohn's disease
and cola drinks [OR: 2.2 (95% CI 1.5-3.1)],
[including sugar or artificial sweeteners?]
chewing gum [OR: 1.5 (95% CI: 1.1-2.1)]
and chocolate consumption [OR: 2.5 (95% CI: 1.8-3.5)]
but a negative association with
citrus fruit consumption [OR: 0.5 (95% CI 0.3-0.7)].

Mercola 1999`antibiotics that helped:

. Crohn's patients in Mediterranean countries
appear to have an inordinately high incidence of
gastrointestinal infection with the
Helicobacter pylori (ulcer-causing) bacterium.

. researchers wondered whether H. pylori treatment
might reduce ulcerative symptoms in Crohn's patients.
To test this theory, they gave 30 H. pylori-positive patients
with early-stage Crohn's disease
antibacterial drug therapy for 10 weeks.
Another 40 H. pylori-negative patients received prednisolone,
a standard medication used to fight Crohn's disease.
"after treatment, clinical remission (of Crohn's disease)
was achieved in all patients"
-- regardless of the type of therapy received.
At the same time, H. pylori infection
was eradicated in 28 of the 30 infected patients.

[. even in patients where the bacteria wasn't controlled;
antibiotic treatment reduced symptoms of
early-stage Crohn's disease,
either by reducing H. pylori load
or eliminating some other bacterial problem.
. yet prior antibiotics use increases risk?
perhaps it is when antibiotics are withdrawn,
the bad bacteria grow even more numerous than before.]

Mercola 2003`immune stimulants that helped:

Crohn’s disease and ulcerative colitis,
are inflammatory bowel diseases (IBD).
. [in one study]
recurrent antibiotic-resistant pneumonia
preceded the Crohn’s in every case.
This is important because antibiotics are known to
increase the risk of fungal infection.
. carbohydrates a possible culprit.
Two of three worldwide studies found
the average intake of carbohydrates
(including bread, potatoes, and refined sugars)
to be much greater in those who developed IBD
than in those who did not.
Why would carbohydrates be implicated as a cause?
they are commonly contaminated with fungal toxins,
[ also, they increase fungal growth
that in turn results in fungal toxins;
and either the fungus itself or its toxins
are affecting immune response.]

Most antibiotics are mycotoxins--fungal derivatives.
Mycotoxins are commonly found in our grain food supply.
Mycotoxins can suppress our normal immune function.
Therefore, anyone who has taken an antibiotic
or consumes grains or sugar
qualifies as a potentially immunocompromised person.
. a low-carb diet is antifungal medication:
A 1944 Johns Hopkins Clinical Mycology book
stressed the importance of following a low-carb diet
while treating yeasts.

Crohn’s disease improved on an immune stimulant:
Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF).
of the initial 15 patients in the study,
12 did "significantly" better overall,
while eight went into complete remission!
[ this is significant because,
Crohn’s disease is sometimes seen as
a problem with autoimmunity,
suggesting the immune system is too active;
yet stimulating the immune system in a special way
reduced the damage done by Crohn’s disease.]

a common fungal infection is Candidasis:

Chronic Candidasis is a controversial diagnosis:
[source is a dead link]

Chronic Candidiasis:
doctors say it doesn't exist.

What Predisposes You To Chronic Candida Overgrowth?
Recurrent antibiotic use, steroid drugs,
use of acid blockers, birth control pills,
excessive sugar and refined carb's;
alcohol, diabetes, decreased immune function,
severe chronic stress.

What about Drugs versus Natural Antifungals?
[certain unconventional doctors suggest]
antifungal medication may need to be taken
relatively long term in more severe cases.
Those medicines are Nystatin capsules
or powder ( not the tablets), Nizoral,
or the very expensive Diflucan, and Sporonox.

Additionally there are a number of
natural antifungal agents:
Tannins and grapefruit seed extract.

It is important to restore the normal
acidophilus and bifidus organism in the GI tract
which are killed with antibiotics
and predispose to candida.

If there is a situation of low stomach acidity,
betaine HCL needs to be added
as the candida organisms thrive best in
an alkaline environment.


Candida infection, or candidiasis,
is a fungal infection that can be caused by
an overgrowth of one of 20
naturally occurring species of yeast.

One of vitamin D’s role in the body is to produce
an anti-microbial peptide called cathelicidin.
Cathelicidin is a critical component to
the body’s ability to fight off infections,
such as Candida.

In the present study, researchers measured vitamin D levels
among patients with candidiasis
and found a high prevalence of vitamin D deficiency
in this patient population.

In addition, they administered activated vitamin D
in varying doses to mice infected with Candida.

They found that low doses of activated vitamin D
reduced the fungal burden and led to better survival
compared to mice not given activated vitamin D.
On the other hand, they found that
high doses of activated vitamin D
led to poor outcomes in these mice.

“Mechanistically, low dose [activated vitamin D]
induced proinflammatory immune responses,”
“These beneficial effects were negated with higher vitamin D3 doses.”

J Infect Dis. 2015:
Bimodal Influence of Vitamin D in Host Response
to Systemic Candida Infection-Vitamin D Dose Matters.
Vitamin D level is linked to susceptibility to infections,
but its relevance in candidemia is unknown.
We aimed to investigate the in vivo sequelae of vitamin D3 supplementation
in systemic Candida infection.
Implicating the role of vitamin D in Candida infections,
we showed that candidemic patients had significantly
lower 25-OHD concentrations. Candida-infected mice
treated with low-dose 1,25(OH)2D3
had reduced fungal burden and better survival
relative to untreated mice. Conversely,
higher 1,25(OH)2D3 doses led to poor outcomes.
Mechanistically, low-dose 1,25(OH)2D3 induced
proinflammatory immune responses.
This was mediated through suppression of SOCS3 and induction of
vitamin D receptor binding with the vitamin D-response elements
in the promoter of the gene encoding interferon γ.
These beneficial effects were negated with higher vitamin D3 doses.
While the antiinflammatory effects of vitamin D3
are well described, we found that, conversely,
lower doses conferred proinflammatory benefits in Candida infection.
Our study highlights caution against extreme deviations of
vitamin D levels during infections.

certain emulsions may be inflammatory:

Nature. 2015:
Dietary emulsifiers impact the mouse gut microbiota
promoting colitis and metabolic syndrome.
The intestinal tract is inhabited by a large and diverse
community of microbes collectively referred to as
the gut microbiota. While the gut microbiota provides
important benefits to its host,
especially in metabolism and immune development,
disturbance of the microbiota-host relationship
is associated with numerous chronic inflammatory diseases,
including inflammatory bowel disease
and the group of obesity-associated diseases
collectively referred to as metabolic syndrome.
A primary means by which the intestine
is protected from its microbiota
is via multi-layered mucus structures
that cover the intestinal surface,
thereby allowing the vast majority of gut bacteria
to be kept at a safe distance from epithelial cells
that line the intestine.
Thus, agents that disrupt mucus-bacterial interactions
might have the potential to promote diseases
associated with gut inflammation.
Consequently, it has been hypothesized that
emulsifiers, detergent-like molecules
that are a ubiquitous component of processed foods
and that can increase bacterial translocation
across epithelia in vitro,
might be promoting the increase in inflammatory bowel disease
observed since the mid-twentieth century.
Here we report that, in mice, relatively low concentrations of
two commonly used emulsifiers, namely
carboxymethylcellulose and polysorbate-80,
induced low-grade inflammation and obesity/metabolic syndrome
in wild-type hosts and promoted robust colitis
in mice predisposed to this disorder.
Emulsifier-induced metabolic syndrome was associated with
microbiota encroachment, altered species composition
and increased pro-inflammatory potential.
Use of germ-free mice and faecal transplants indicated that
such changes in microbiota were necessary and sufficient
for both low-grade inflammation and metabolic syndrome.
These results support the emerging concept that
perturbed host-microbiota interactions
resulting in low-grade inflammation
can promote adiposity and its associated metabolic effects.
Moreover, they suggest that the broad use of emulsifying agents
might be contributing to an increased societal incidence of
obesity/metabolic syndrome and other chronic inflammatory diseases.

Mercola's comment of that study:

Most processed foods contain any number of additives,
like artificial flavors, colors, preservatives;
and emulsifiers.
. Similar emulsifiers include lecithin*,
carrageenan, polyglycerols, and xanthan gum.
*: [3.5: could lecithin be bad?
it might depend on what it's emulsifying;
eg, krill oil is an emulsion,
and it's considered good for inflammatory bowels.]

. the emulsifiers caused chronic colitis in
mice with already abnormal immune systems.
In mice with healthy immune function,
they resulted in mild intestinal inflammation
and subsequent metabolic dysfunction that led to
obesity, hyperglycemia, and insulin resistance.

Most notably, the emulsifiers were fed at levels that
an average person would be exposed to
if eating a lot of processed foods,
suggesting these additives may indeed affect our health.

Mercola 2012`an emulsion that works:

. animal research in Gastroenterology
found dietary supplementation with krill oil
offered several protective effects against
inflammatory bowel disease,
including a reduction in inflammation and oxidative stress,
and preservation of colon length.
[Scandinavian Journal of Gastroenterology, 2011]
The omega-3 fats in krill oil, EPA and DHA,
play an important role in inflammation;
they produce compounds called resolvins and protectins.

A 2007 study investigated krill oil's
ability to reduce inflammation.
. 300 mg krill oil per day significantly reduced
inflammation, pain, stiffness and functional impairment
after just 7 days, and even more profoundly after 14 days.
[J American College of Nutrition 2007]

Mice consuming krill oil showed less joint inflammation
from rheumatoid arthritis than did the control group.
[BMC Musculoskeletal Disorders, 2010]

Aside from the omega-3 fats, krill oil also contains
astaxanthin, a carotenoid and potent antioxidant;
and a suppressor of inflammatory mediators
—including tumor necrosis factor alpha,
nitric oxide, COX-1 and COX-2 enzymes.

krill oil typically provides 14 % EPA and DHA,
along with 0.2 % naturally occurring astaxanthin.
[Functional Ingredients 2010]
Fish oil provides 30 % EPA and DHA.
However, 80-85 % of fish oil is never absorbed.
The amazing beauty of krill is that it is already in
the correct, phosphatidyl choline-bound form
so your body uses virtually 100 percent of it.
Unlike fish oil it contains 69 different phospholipids,
9 of which are omega-3 fatty acid bound.
Phospholipids can act as emulsifiers,
enabling oils to form a colloid with water,
basically enhancing the absorption and transport
of the fats to which they are bound.
[Lipids 2011]

If you have IBD, including Crohn's disease:

Take krill oil as an anti-inflammatory;
much better than plant-based omega-3 such as flax;
Avoid all types of sugars, particularly fructose,
as these will increase inflammation
by increasing your insulin levels
[by causing insulin resistance;
and refined carbs feed yeasts that may
compromise the immune system.]
Also avoid grains until your symptoms are under control.
Avoid the artificial sweeteners,
saccharin and sucralose.
Vitamin D appears to be nearly as effective as
animal-based omega-3 fats in countering IBD.
vitamin D results in over 200 anti-microbial peptides
that help fight all sorts of infections.
turmeric is anti-inflammatory.
compare boswellia herb to conventional drugs.

Get plenty of beneficial bacteria either through
fermented foods or probiotics (live germ pills).
. people who took the bacteria Bifidobacterium infantis
had lower levels of inflammation.
. the most effective probiotic is the fecal transplant;
the transplants showed promise in the treatment of
ulcerative colitis and Crohn's disease,
with symptoms improving in days to weeks.
-- far less invasive than surgery,
and with far fewer side effects than drugs.

3.5: badgut.org`beware saccharin and sucralose:

Qin argued that saccharin, an earlier artificial sweetener
that has a similar effect on the gut as sucralose,
might be one of the most important risk factors for IBD.

Med Hypotheses. 2002:
Impaired inactivation of digestive proteases
by deconjugated bilirubin:
the possible mechanism for inflammatory bowel disease.
Inflammatory bowel disease refers to
ulcerative colitis and Crohn's disease.
The dramatic increase in the last half century
and the big difference in incidence for people with
the same ethnic background but living in different areas
strongly suggested that environmental factors
played the dominant role for these diseases.
The similarity in many aspects for these two diseases
suggested a common causative factor.
Here I suggest the impaired inactivation of digestive proteases
by deconjugated bilirubin, as the result of
the inhibition of bilirubin deconjugation enzyme, beta-glucuronidase,
originated from the luminal bacteria and mucosa of the gut,
to be a possible mechanism for both ulcerative colitis
and Crohn's diseases.
I also provide evidence to suggest that saccharin
could be the causative or one of the most important risk factors
for inflammatory bowel disease
as for its inhibition on beta-glucuronidase in the intestine.

Qin tracked the use of saccharin
over different time durations and locations.
In the United States, for example,
the consumption of saccharin skyrocketed
from the 1950s to the peak of its popularity
in the 1960s and early 1970s.
Similarly, the incidence of IBD
increased dramatically during that period.
When saccharin consumption declined in the 1980s,
with FDA rules restricting its use
(due to its cancer-causing properties),
the incidence of IBD also decreased.

In 1995, even with restrictions on its use in foods,
Americans consumed 4,500 tonnes of saccharin,
those in Western Europe consumed 4,100 tonnes,
and the population of Japan consumed a mere
140-150 tonnes of the sweetener.
Supporting Qin’s hypothesis,
the incidence of IBD in those three regions
is proportional to their consumption of saccharin.
Many studies have pointed to sugar
as a consistent dietary risk factor for IBD,
but Qin suggested that it might not be sugar itself
but the demand for more sweet things in the diet
and, specifically, an increased consumption of saccharin
that is the real risk factor for IBD.

What that earlier paper could not explain, however,
was the significantly greater incidence of IBD in Canada
than anywhere else in the world,
especially since Canada has had
more stringent saccharin-restricting rules
during the past three decades than most other countries.
If saccharin is the major risk factor that Qin proposed,
shouldn’t Canada’s incidence of IBD be
lower than in other developed countries?

In this latest hypothesis,
Qin now follows the trail to sucralose for clues.
Sucralose, which has been widely used in Canada
longer than in any other country,
is twice as sweet as saccharin.
Extrapolating from recent research, Qin contends that
sucralose is likely even more destructive than saccharin
to the gut. Canada was the very first country
to approve the use of sucralose in the early 1990s
– shortly before the incidence of
Crohn’s disease and ulcerative colitis in this country
began to grow at an unprecedented rate.

There is also increasing evidence that
regular consumption of sucralose
has significant adverse effects on the gut,
such as suppressing beneficial bacteria
and altering microbial composition.

J Toxicol Environ Health A. 2008:
Splenda [sucralose] alters gut microflora and increases intestinal
p-glycoprotein and cytochrome p-450 in male rats.
Splenda is comprised of the high-potency
artificial sweetener sucralose (1.1%)
and the fillers maltodextrin and glucose.
Splenda was administered by oral gavage
at 100, 300, 500, or 1000 mg/kg
to male Sprague-Dawley rats for 12-wk,
during which fecal samples were collected weekly
for bacterial analysis and measurement of fecal pH.
After 12-wk, half of the animals from each treatment group
were sacrificed to determine the intestinal expression of the
membrane efflux transporter P-glycoprotein (P-gp)
and the cytochrome P-450 (CYP) metabolism system by Western blot.
The remaining animals were allowed to recover for an additional 12-wk,
and further assessments of fecal microflora, fecal pH,
and expression of P-gp and CYP were determined.
At the end of the 12-wk treatment period,
the numbers of total anaerobes,
bifidobacteria, lactobacilli, Bacteroides, clostridia,
and total aerobic bacteria
were significantly decreased;
however, there was no significant treatment effect on
enterobacteria. Splenda also increased fecal pH
and enhanced the expression of P-gp by 2.43-fold,
CYP3A4 by 2.51-fold,
and CYP2D1 by 3.49-fold.
Following the 12-wk recovery period,
only the total anaerobes and bifidobacteria
remained significantly depressed,
whereas pH values, P-gp, and CYP3A4 and CYP2D1
remained elevated. These changes occurred at Splenda dosages
that contained sucralose at 1.1-11 mg/kg
(the US FDA Acceptable Daily Intake for sucralose is 5 mg/kg).
Evidence indicates that a 12-wk administration of Splenda
exerted numerous adverse effects, including
(1) reduction in beneficial fecal microflora,
(2) increased fecal pH, and
(3) enhanced expression levels of P-gp, CYP3A4, and CYP2D1,
which are known to limit the bioavailability
of orally administered drugs.
“The reduction in intestinal bacteria in this study
was accompanied by an increase in fecal pH
that typically occurs when there is a decrease in
the production of short-chain fatty acids (SCFA)
by colonic bacteria. SCFA decrease luminal pH
and hence provide antagonistic properties against
intestinal pathogens and invading organisms.
Suppression of bacteria, alterations in microbial composition,
and reduction in SCFA in the gut
might have clinical significance for humans
in the management of many medical conditions
such as irritable bowel syndrome,
inflammatory bowel disease,
cardiovascular disease, obesity, and cancer,
in which gut flora play an important role.”

“At the end of the 12-wk treatment with Splenda,
numerous alterations were observed including
lymphocytic infiltrates into epithelium,
epithelial scarring, mild depletion of goblet cells,
glandular disorganization, and focally dilated vessels
stuffed with intravascular lymphocytes.”

The Canadian Journal of Gastroenterology. 2011:
Qin X. What made Canada become a country with the
highest incidence of inflammatory bowel disease:
Could sucralose be the culprit?
Inflammatory bowel disease (IBD) (which includes both
ulcerative colitis and Crohn’s disease [CD])
emerged and dramatically increased in the past century (1).
Early studies revealed that IBD was most prevalent in
countries such as the United Kingdom, the United States and
those in northern Europe (1). Compared with these countries,
the prevalence of IBD in Canada was much lower.
This was demonstrated in early epidemiological studies
conducted in Canada.
According to a review by Mayberry and Rhodes (2),
a study published in 1972 reported the
incidence and prevalence of CD in Sherbrooke, Quebec,
at only 0.7 and 6.3 per 100,000 population, respectively,
which were much lower than countries such as the
United Kingdom, the United States, Sweden, Denmark,
and even Israel and New Zealand
at the same time or even decades earlier.
However, studies in recent years
have suddenly found that Canada has become
a country with the highest incidence of IBD (3).
For example, the prevalence of CD in Alberta in 1981
was only 44 per 100,000 population (4),
compared with 91 per 100,000
in Olmsted County, Minnesota (USA) on January 1, 1980 (5).
However, the prevalence of CD in Alberta
increased to 283 per 100,000 on July 1, 2000 (3),
compared with 174 per 100,000
in Olmsted County in January 1, 2001 (6).
It would be valuable to know what caused
the dramatic increase of IBD in Canada
because it may provide critical information regarding its etiology.

A decade ago, a series of accidental findings
made me suspect that the impaired
inactivation of digestive proteases
due to the inhibition of gut bacteria by dietary chemicals,
such as saccharin,
play a causative role in IBD as a result of the
accelerated degradation of the mucous layer
and underlying endothelium (7).
It provided an explanation for many puzzles in IBD
such as the dramatic increase of IBD in the 1950s and 1960s,
and its levelling off since the latter part of the 1970s,
as observed in many western countries including Canada (4,7).
However, this hypothesis was challenged by the
failure to provide an explanation for the
recent high incidence of IBD in Canada,
which had adopted more stringent standards for
the use of saccharin
than most other western countries after the
finding of carcinogenic effects of saccharin
on the bladders of experimental animals in 1977.

If not saccharin, then what caused
the remarkable increase of IBD in Canada?
I suggest that sucralose may be the culprit.

In 1991, Canada was the first country
to approve the use of sucralose (8).
Interestingly, the study by Wrobel et al (9) reported that
the incidence of pediatric IBD in Southern Alberta was
2.3 (per 100,000 population) between 1983 and 1987,
2.5 between 1988 and 1992,
5.0 between 1993 and 1998, and
6.5 between 1999 and 2005 (9),
indicating a dramatic increase in the early 1990s.
Could sucralose cause the increase of IBD in Canada? How?

Similar to saccharin, sucralose can also exert
potent inhibition of gut bacteria (10).
However, it may have a more pronounced effect on gut bacteria
than saccharin in that approximately 65% to 95% of sucralose
is excreted through the feces unchanged (10),
while a large proportion of saccharin
is absorbed and eliminated through urine;
the acceptable daily intake of sucralose is 15 mg/kg,
but only 5 mg/kg for saccharin.
As I suggested a decade ago,
regarding the possible risk of saccharin on IBD (7),
sucralose may have a similar but stronger impact
on gut bacteria, digestive protease inactivation
and gut barrier function.