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Dietary Supplement Therapies for Inflammatory Bowel Disease: Crohn’s Disease and Ulcerative Colitis



Inflammatory bowel disease (IBD) including ulcerative colitis and Crohn’s disease are chronic relapsing and remitting chronic diseases for which there is no cure. The treatment of IBD frequently requires immunosuppressive and biologic therapies which carry an increased risk of infections and possible malignancy. There is a continued search for safer and more natural therapies in the treatment of IBD. This review aims to summarize the most current literature on the use of dietary supplements for the treatment of IBD. Specifically, the efficacy and adverse effects of vitamin D, fish oil, probiotics, prebiotics, curcumin, Boswellia serrata, aloe vera and cannabis sativa are reviewed.
Title Page
Title: Dietary Supplement Therapies for Inflammatory Bowel Disease: Crohn’s Disease and Ulcerative
Running Title: Alternative therapy in IBD
Alyssa Parian, MD (Corresponding author)
Assistant Professor
Johns Hopkins School of Medicine
Department of Gastroenterology
4940 Eastern Avenue, A-Building 502
Baltimore, MD 21224
P: 410-550-5122
F: 410-550-7861
Berkeley N. Limketkai, MD
Clinical Assistant Professor
Stanford University School of Medicine
Division of Gastroenterology and Hepatology
Dietary Supplement Therapies for Inflammatory Bowel Disease: Crohn’s Disease and Ulcerative
Inflammatory bowel disease (IBD) including ulcerative colitis and Crohn’s disease are chronic relapsing
and remitting chronic diseases for which there is no cure. The treatment of IBD frequently requires
immunosuppressive and biologic therapies which carry an increased risk of infections and possible
malignancy. There is a continued search for safer and more natural therapies in the treatment of IBD. This
review aims to summarize the most current literature on the use of dietary supplements for the treatment
of IBD. Specifically, the efficacy and adverse effects of vitamin D, fish oil, probiotics, prebiotics,
curcumin, Boswellia serrata, aloe vera and cannabis sativa are reviewed.
The inflammatory bowel diseases (IBD) of Crohn’s disease (CD) and ulcerative colitis (UC) are relapsing
and remitting chronic diseases of the gastrointestinal tract. The pathogenesis of IBD has not been well
elucidated, but studies so far support a multifactorial process involving genetics, environment exposures,
and the gut microbiome. There are 163 known IBD risk genes that partly explain the development of IBD
in the population.(1) Environmental factors, such as diet, medications, and hygiene, appear to
demonstrate a role in IBD pathogenesis.(2-4) Further support for the presence of environmental triggers
in IBD come from migrant studies that have demonstrated an increased incidence of IBD among those
who migrate from regions of lower IBD incidence to regions of higher incidence.(5) Alterations in the gut
microbiome, through antibiotic use (3) or acute gastroenteritis (6, 7) have been shown to increase the risk
of developing IBD.
Most IBD patients will eventually require immunosuppressant therapy to control their disease. However,
currently available medications have limitations, and despite the availability of powerful therapies, half of
CD patients may still require surgery within 10 years after diagnosis.(8) Even the anti-tumor necrosis
factor (anti-TNF) therapies – among the most potent immunosuppressants used for IBD – only has
modest response rates.(9) The additional concern with traditional immunosuppressants is the potential for
serious adverse events, such as infections (tuberculosis, reactivation of hepatitis B and fungal infections),
malignancies (lymphomas and skin cancers) and skin reactions. There is a continued search for safer and
more natural therapies to treat IBD. This review discusses the current literature on the use of selected
dietary supplement therapies for the treatment of IBD, specifically, vitamin D, fish oils, probiotics,
prebiotics, curcumin, Boswellia serrata, Aloe vera, and Cannabis sativa. The role of diet, other alternative
therapies and nutritional deficiencies in IBD are also important but were outside of the scope of this
Vitamin D
Vitamin D is a fat-soluble hormone that includes ergocalciferol (D2) and cholecalciferol (D3). Sources of
vitamin D in humans include diet, vitamin supplements, and endogenous synthesis through sunlight
(ultraviolet B) exposure. Foods rich in vitamin D include fatty fish, cod liver oil, beef liver, egg yolks, and
vitamin D-fortified milk.
Vitamin D has traditionally been associated with bone health, but more recently discovered to possess
immunomodulatory properties. Some immunologic effects of vitamin D include impairment of
lymphocyte proliferation, expansion of regulatory T cells, and modulation of inflammatory cytokine
release.(10-15) Consequently, a deficiency in vitamin D has been associated with several autoimmune
disease, such as multiple sclerosis,(16) rheumatoid arthritis,(17) and systemic lupus erythematosus.(18)
Early murine studies have also shown a relationship between vitamin D and IBD (both CD and UC) [CD
or UC, it’s important to differentiate, or at least say there was none]. Vitamin D receptor (VDR) knockout
led to more severe colitis than VDR wild-type in an IBD mouse model.(19) In another experiment,
vitamin D-sufficient mice did not develop IBD symptoms, while vitamin D-deficient mice experienced
diarrhea, wasting disease, and death.(20) In humans, epidemiologic studies have shown a higher
incidence of IBD in northern latitudes, where sunlight exposure and natural vitamin D synthesis are
lower.(21, 22) Low sunlight exposure has also been associated with an increased risk for hospitalizations
and bowel surgeries related to IBD,(23) and normalization of vitamin D-deficient levels in CD may lead
to lower rates of hospitalization and surgery.(24) An analysis of the prospective Nurses’ Health Study
additionally revealed that 25-hydroxyvitamin D protected against CD, but not UC.(25) Smaller studies in
CD patients have shown a trend toward decreased relapse rates and lower disease activity scores.(26, 27)
Although there are suggestions in animal studies, epidemiologic data, and small cohort studies that
vitamin D may improve IBD (11, 15, 24-38), the evidence is still circumstantial. Larger and more robust
randomized controlled trials are needed to determine whether vitamin D can indeed influence disease
activity and to what degree. Moreover, although < 20 ng/mL vitamin D is considered “deficient” in adults,
and levels between 20 and 30 ng/mL are considered “insufficient”, the optimal dose for
immunomodulation is unclear. In any case, vitamin D deficiency occurs frequently in IBD patients due to
increased sun avoidance while on thiopurines, small bowel inflammation causing relative malabsorption,
ileal resection affecting bile salt resorption, and increased stool excretion.(39-43) Vitamin D levels should
be checked and repleted as needed in IBD patients.
Fish Oils
The fatty acids most implicated in the inflammatory pathway include the omega-3 and omega-6
polyunsaturated fatty acids.(44) Omega-3 fatty acids are believed to possess immunomodulatory
properties, while omega-6 fatty acids possess pro-inflammatory properties. Since fish oil is a rich source
of omega-3 fatty acids, there have been multiple research studies assessing the role of fish oil in the
induction and maintenance of remission in IBD.
Crohn’s Disease. Diets high in omega-3 fatty acids may be associated with a lower risk of developing
Crohn’s.(45) For CD, although there are no randomized trials that evaluated the use of fish oil for
induction of remission, several exist that evaluate fish oil for maintenance of remission. Two large multi-
national randomized controlled trials found no difference in relapse rates between participants
administered omega-3 fatty acid capsules or placebo.(46) However, a subsequent meta-analysis that
included these two trials showed some benefit of omega-3 fatty acids over placebo(47). Potential
limitation raised by the authors of the meta-analysis is the heterogeneity among the included studies.
Therefore, the utility of fish oil for the induction of remission is still unclear. Fish oil therapy may be
more efficacious for Crohn’s colitis rather than ileitis. (48) Additionally, fish oil may act synergistically
with mesalamine therapy. (49) The benefit of fish oil may however be greatest among IBD patients with
essential fatty acid deficiency.(50)
Ulcerative Colitis. An early study evaluating the treatment of both UC and CD with fish oil concluded the
clinical benefit was confined to UC patients.(51) For active UC, two small cross-over studies (17 and 24
patients, respectively) and a randomized trial (18 patients) found greater improvement in clinical and
histologic scores among participants administered fish oil when compared with placebo.(52-54) A
subsequent trial of 121 UC patients showed a more rapid reduction in prednisone dose among those who
received fish oil-enriched supplement (also including fructooligosaccharides, gum arabic, vitamin C,
vitamin E, and selenium), compared with a carbohydrate-based placebo formula, but otherwise found no
difference in clinical, endoscopic, or histologic scores.(55) A small cross-over trial of 10 UC patients
found that, compared with sulfasalazine (2 grams per day), fish oil was associated with greater
inflammation by serology (C-reactive protein, erythrocyte sedimentation rate, platelets), lower
sigmoidoscopic activity, and otherwise no difference in histologic scores.(56) These findings suggest that
sulfasalazine may be superior to fish oil for mild-to-moderate UC. For the maintenance of remission in
UC, three randomized trials that compared fish oil with placebo in 138 patients did not show a difference
in relapse rates.(57-59)
Probiotics are live microorganisms that confer a health benefit on the host. (60) (61) Probiotics are
believed to work through several different mechanisms: by decreasing pro-inflammatory cytokine
secretion, increasing anti-inflammatory cytokine secretion, inducing regulatory T cells, (62) decreasing
intestinal permeability (63) and increasing production of short chain fatty acids. (63) Probiotics aim to
alter the microbiome towards a more favorable, anti-inflammatory species of bacteria. (64, 65)
VSL #3 (Sigma-Tau Pharmaceuticals, Gaithersburg, MD) is one of the most studied probiotics for the
treatment of IBD. It contains three genera of bacteria: Lactobacilli (L casei, L plantarum, L acidophilus,
L delbrueckii), Bifidobacteria (B longum, B breve, B infantis), and Streptococcus (S salivarius).
Ulcerative colitis – Two studies of VSL#3 on active UC found VSL#3 induced remission in greater than
50% of patients with no control group for comparison. (66, 67) Tursi et al. compared VSL#3 plus
balsalazide to both balsalazide alone or mesalazine alone in active UC patients and showed the VSL#3
combination with balsalazide was faster in obtaining remission and improved endoscopic and histologic
inflammation compared to the other two therapies. (68) Three placebo-controlled trials reported that
VSL#3 3600 billion CFU/daily (or weight adjusted for children) was superior in improving symptomatic
scores, inducing remission, maintaining remission and decreasing rectal bleeding in UC patients. (69-71)
A meta-analysis in 2012 concluded that 3600 billion bacteria daily of VSL#3 induced remission in UC
70% more frequently than placebo. (72) The newest meta-analysis from 2014 found a 2.4 fold increase in
remission rate with the use of VSL#3 3600 billion colony forming units daily compared to placebo
without any serious side effects. (73)
Pouchitis. The best data for the use of VSL#3 is in pouchitis prevention in UC patients with recurrent
pouchitis. Compared to placebo, VSL#3 was more likely to keep pouchitis patients in remission after
initial induction with antibiotics (p < 0.001). (74, 75) One study showed contradictory results without
higher rates of remission with VSL#3 use, although there was a high drop-out rate with a small
population.(76) Pronio et al. compared VSL#3 to placebo for 12 months in asymptomatic patients who
have undergone ileal pouch anal anastomosis (IPAA). VSL#3 treated patients had better pouchitis disease
activity index scores and an expanded number of mucosal regulatory T cells. (77) A systematic review
from 2012 concluded that VSL#3 significantly prevents relapses in IPAA patients (72) and the current
guidelines recommend VSL#3 for the prevention of recurrent pouchitis. (78)
Mild active pouchitis in 23 patients was treated with VSL#3 with 69% of patients achieving remission.
(79) Gionchetti et al. also studied whether VSL#3 could prevent the first occurrence of pouchitis in a
placebo controlled trial one week after ileostomy closure. Only 10% of patients treated with VSL#3
developed pouchitis at one year compared to 40% in the placebo group. Additionally, the symptomatic
scores were better in the VSL#3 group with a lower stool frequency and shift towards a less inflammation
pouch microbiotia.(80)
Crohn’s Disease. The studies of VSL#3 in Crohn’s patients are less promising. The largest prospective,
randomized trial in post-operative Crohn’s patients found no difference between patients treated with
VSL#3 versus placebo. However, in patients given VSL#3 within 90 days of the surgery, there was a
trend towards significance suggesting that timing may play an important role. (81) Four separate
systematic reviews did not find a significant improvement in CD patients treated with VSL#3. (82-85)
Crohn’s Disease. Lactobacillus rhamnosus GG (LGG) has been studied in Crohn’s disease without an
appreciable benefit on post-operative disease recurrence, (86) induction or maintenance of remission in
adult Crohn’s patients, (87) or the maintenance of remission in pediatric patients when added to standard
therapy.(88) In UC patients, LGG appears to have a more beneficial effect by prolonging remission.(89)
Another study showed acute pouchitis patients treated with LGG had a positive change in the pouch
microbiome, but experienced no clinical improvement. (90) However, if LGG was given immediately
after IPAA surgery, it was been shown to delay the first episode of pouchitis. (91)
Lactobacillus johnsonii, LA1, was studied in two trials for the prevention of post-operative recurrence in
Crohn’s patients. Both were randomized, placebo-controlled studies with > 50 patients each and neither
found a decrease in post-operative recurrence with the use of LA1. (92, 93) There are no published trials
of this particular strain of probiotic in UC patients.
Saccharomyces boulardii
Saccharomyces boulardii is a nonpathogenic strain of yeast that appears to have probiotic qualities with
some data to support its use in the prevention of Clostridium difficile relapses. (94, 95)
Ulcerative Colitis. In UC patients, one trial found 17 (71%) of 24 patients with mild to moderate activity
given S. boulardii plus mesalamine attained clinical and endoscopic remission suggesting S. boulardii
may be effective in treating active UC; however, there was no comparison control group.(96) A small case
series of 6 patients with left sided UC treated with S. boulardii plus rifaximin all had improvement in
symptoms. (97) Larger, placebo-controlled studies are warranted for the use of S. boulardii in UC.
Crohn’s Disease. In CD patients, S. boulardii was shown to decrease the number of daily bowel
movements (98) and maintain remission. (99) S. boulardii has also been found to improve intestinal
permeability in Crohn’s patients. (63) However, a large randomized, placebo-controlled trial found S.
boulardii was not effective in maintaining remission in CD patients after induction with steroids or
salicylates. (100) The addition of S. boulardii to standard Crohn’s therapy has not been evaluated yet and
further studies are needed to determine its role in CD treatment.
Escherichia coli Nissle 1917
Ulcerative Colitis. Escherichia coli Nissle 1917 (EcN) was found to be equivalent to low dose
mesalamine in maintaining remission of UC. (101, 102) One study showed EcN enemas to be equally as
effective as mesalamine in treating distal UC.(103) A dose-finding multicenter trial of EcN enemas was
performed on 90 patients with ulcerative proctitis or proctosigmoiditis. Due to the large drop-out rate, the
intention to treat analyses were not significant; however, per protocol analysis showed a dose dependent
efficacy and histologic improvement. At least half of the premature discontinuations were due to lack of
efficacy and the rest were due to adverse events including flatulence and “other gastrointestinal
disorders.”(104) The most recent study of 100 patients did not find EcN to have a benefit as an add on
therapy in the treatment of active UC. (105) There does appear to be a certain subset of patients that EcN
may provide benefit to, although further studies are needed to determine which patient characteristics are
associated with response rates.
Overall IBD Reviews. Systematic review and meta-analyses have been difficult to perform on the efficacy
of probiotic therapy in the treatment of IBD due to such large variation in probiotic strains, dosages used,
concomitant therapy allowed, and measured outcomes. One meta-analysis suggested that probiotics are
superior to placebo in maintaining remission in ulcerative colitis. (106)
Prebiotics are non-digestible carbohydrates that selectively promote the growth of commensal
microorgamisms within the gut and improve the well-being of the host.(107) Prebiotics pass through the
upper GI tract undigested and act as a food source for commensal bacterial in the distal small bowel and
colon. Through fermentation of prebiotics, short chain fatty acids such as butyrate are produced which are
known to have anti-inflammatory effects on the colon. Prebiotics are best known for their effects on
healthy stool regulation by increasing fecal water content in patients with constipation and bulking the
stool in patients with diarrhea.
Oligofructose. Prebiotics specifically select for specific bacterial strains known to be beneficial to the
health of the GI tract such as Lactobacillus and Bifidobacterium and select against other strains known to
be harmful and proinflammatory such as Bacteriodes, Klebsiella and Streptococcus viridans. The
prebiotics inulin and oligofructoses have been shown to increase the levels of Lactobacilli and
Bifidobacteria in the colon. (60)
Inulin. This prebiotic has been shown to decrease reactive oxygen species and improve the severity of
inflammation in a rodent model of colitis. (108) In human subjects, 12 g of inulin daily was shown to
decrease fecal inflammatory markers in patients with active UC. (109) Treatment of pouchitis with 24 g
of oral inulin led to improvement in endoscopic and histologic inflammation, decreased B. fragilis
concentration and increased levels of butyrate compared to placebo. (110) Crohn’s patients also benefited
from treatment with inulin. Inulin, 10 g twice a day, led to an increased fecal concentration of butyrate
compared to placebo in CD patients. (111)
Fructooligosaccharides. These decrease intestinal inflammation and selectively alter the colonic bacteria
towards anti-inflammatory species. (112-114) A small open-label study of 10 CD patients with active
ileocolitis had improvement on the Harvey-Bradshaw index and an increased concentration of
Bifidobacteria. (115) However, a large placebo-controlled trial found no difference in clinical response
but did note a large drop-out rate in those treated with FOS due to abdominal bloating and gas. (116)
Germinated barley foodstuff (GBF) is another prebiotic with promising anti-inflammatory properties
demonstrated in rodent models. (117, 118) GBF appears to decease inflammation by reducing serum
TNF-alpha, IL-6 and IL-8 levels. (119) Several small pilot studies show promise in the treatment of active
UC with improvement in clinical activity scores, endoscopic scores and fecal butyrate levels. (120) (121)
(122) A placebo-controlled study of 59 UC patients in remission found that GBF + standard therapy
prolonged remission compared to placebo + standard therapy. (123) A second placebo controlled study of
active UC disease demonstrated GFB caused a decrease in CRP and abdominal cramping.(124)
IBD Overall. Controlled studies on prebiotics in IBD are limited presently and side effects such as
bloating, abdominal discomfort and flatulence are common with high doses of prebiotic therapy.
Prebiotics may be efficacious when used in combination with standard therapy especially in ulcerative
colitis patients. High doses of fiber are contraindicated in CD patients with active stricturing disease and
this therapy should be tailored to each individual patient. IBD patients should be referred to registered
dietitian nutritionists for nutritional counseling.
Turmeric, a commonly used Asian spice, contains curcumin which has been used for centuries as a topical
natural therapy for intestinal and skin disorders. Curcumin has since proven to possess anti-inflammatory
properties by inhibiting NF-κB thereby decreasing production of proinflammatory cytokines. (125-127)
Curcumin also has immunosuppressant properties through the inhibition of TNF-α and IL-2 production.
(126, 128) Curcumin acts topically without significant systemic absorption giving it an excellent safety
profile. Rodent studies have shown promising results with both prevention and successful treatment of
induced colitis. (129-133)
One of the first studies of 10 IBD patients (5 CD, 5 ulcerative proctitis) found all UC proctitis patients
symptomatically improved with reduction in medications in four. Of the five CD patients, four had a
decrease in the CDAI score as well as the sedimentation rate. (134) These exciting results led to a large,
randomized, double-blinded, placebo-controlled trial of mild UC patients in clinical remission.
Ulcerative Colitis. Curcumin 1 gram orally two times daily or placebo was given for six months. UC
patients in the treatment arm had improvement in both symptomatic scores as well as endoscopic scores
and a decreased number of disease flares. (135) A trial of curcumin enemas versus placebo was performed
in distal UC patients since curcumin is known to act topically. Unfortunately, there was a high drop-out
rate in this study making the results difficult to interpret. Although, those patients who stayed on the
enema therapy did have symptomatic and endoscopic improvement compared to those receiving placebo.
A multicenter, randomized, placebo-controlled, double-blinded study was performed on 50 patients with
active mild to moderate UC despite maximal oral and rectal mesalamine. Oral curcumin 3 grams daily
with concomitant mesalamine compared to placebo plus mesalamine for one month found curcumin had a
increase in clinical remission (p = 0.01), clinical response (p < 0.001), and endoscopic remission (p =
0.043). The authors concluded that curcumin therapy 3 grams daily in addition to mesalamine therapy
may improve clinical and endoscopic remission in mild to moderate UC. (137)
Colorectal Cancer. Curcumin is also believed to have anti-neoplastic properties against colorectal cancer
(138-140) and has been shown to decrease polyp growth in familial polyposis syndromes. (127)
IBD Overall. Curcumin therapy for the treatment of IBD has excellent promise and is being further
studied for this indication. Due to its topical nature without systemic absorption, curcumin will likely be
best served for ulcerative colitis patients who have inflammation limited to the mucosal layer as opposed
to Crohn’s patients with transmural inflammation. With a good safety profile and patient tolerability,
curcumin is a promising therapy for IBD.
Boswellia serrata
Boswellia serrata is an Ayurvedic herb used for centuries in India as a tradition remedy for the treatment
of various ailments. Boswellia serrata acts on the arachidonic acid cascade and inhibits leukotriene
biosynthesis leading to an overall decrease in proinflammatory cytokines. (141) Animal studies have
shown Boswellia serrata may be an effective therapy for IBD.(142-144) One UC (145) and two CD (146,
147) studies found Boswellia serrata to be equivalent in efficacy to mesalamine therapy for active
Crohn’s Disease. The largest study to date on Boswellia serrata in CD patients was a multicenter,
placebo-controlled, randomized, and double-blinded study in Germany. In total, 108 CD outpatients in
clinical remission were randomized to Boswelan 2400 mg daily or placebo for 52 weeks with
maintenance of remission at 52 weeks as the primary endpoint. Due to a lack of efficacy of Boswelan, the
trial was terminated early without any differences in remission rates, time to relapse or inflammatory
markers. The authors concluded there is excellent tolerability of Boswellia serrata, but no efficacy for
maintaining remission in CD patients. (148)
IBD Overall. There is no data to support the use of Boswellia serrata as monotherapy for Crohn’s disease
and further studies are needed in ulcerative colitis at this time. Further studies investigating the efficacy of
Boswellia serrata are needed for both UC and CD with specific focus on the use of this agent as add on
therapy to standard treatment.
Aloe vera
Aloe vera, part of the lily family, has been used medicinally for over 5,000 years and is thought to have
anti-inflammatory, anti-oxidant, anti-neoplastic and anti-aging properties. (149) Aloe vera has been shown
to have topical anti-inflammatory properties and is superior to placebo in the treatment of plaque
psoriasis. (150) An in vitro study on gastrointestinal mucosa found aloe vera to have dose-dependent anti-
oxidant properties and inhibitory effects on prostaglandin E2 and IL-8. (151)
Ulcerative Colitis. A randomized, double-blinded, placebo-controlled trial was performed with 44 patients
to evaluate the safety and efficacy of 4 weeks of 100 ml aloe vera oral gel in the treatment of mild to
moderate active UC. Clinical remission (SCCAI ≤ 2) and clinical improvement (SCCAI decrease of ≥3)
at 4 weeks trended towards the superiority of aloe vera but did not meet significance with large
confidence intervals suggesting the study may have been underpowered. Clinical response was found in
47% of aloe vera patients and 14% of placebo (OR 5.3; CI 1.0 – 27, p = 0.048). There was improvement
in histological score in patients given aloe vera compared to placebo (p = 0.031). However,
sigmoidoscopic and histologic remission were not achieved. Serum inflammatory markers did not
improve with aloe vera therapy. However, it was well tolerated without any significant adverse events.
IBD Overall. Aloe vera appears to be a possible therapy for mild to moderate colitis and may benefit from
being studied as adjuvant therapy. There is no data on the use of aloe vera for Crohn’s disease currently.
No adverse events have been reported in humans, but a rodent model found Aloe vera supplementation
for 2 years caused an increased rate of adenomas and neoplasms in the large intestines, mucosal
hyperplasia of the large bowel and hyperplasia of the mesenteric lymphoid system.(153)
Toxicities Associated With Herbal Medicines
Herbal medicines, dietary supplements and vitamin are not regulated or approved by the Food and Drug
Administration (FDA) like prescription medical therapy is. Therefore, the appropriate dose, interactions
with other medications and long term adverse effects may not be known. The Dietary Supplement Health
and Education Act (DSHEA) regulate all natural products and do not require additional toxicity studies in
products on the market prior to 1994. The manufacturing of these products is also not tightly controlled
and may contain varying dosages of the active ingredient and unknown contaminants.(153) Due to the
potential benefits these therapies may have, more rigorous testing and regulations are needed to determine
their safety and efficacy.
Cannabis sativa
Cannabis sativa, better known as marijuana, has been shown to have certain medicinal properties
including pain modulation, anti-nausea effects and possibly even anti-inflammatory properties. However,
the psychotropic effects have limited its use and legal availability. Two cannabinoid receptors in the gut
have been identified: cannabinoid receptor 1 and 2, CB1 and CB2.(154) CB1 and CB2 are found within
the enteric nervous system, (155-157) epithelial cells and immune cells.(155) Endogenous
endocannabinoids have been discovered which may modulate intestinal inflammation (158, 159) and
animal models suggest cannabis play a role in the treatment of colitis. (160-164)
Many of patients are already self-treating with cannabis since they cannot find full relief with current
medical therapy.(165) Cannabis may be helpful in treating some of the symptoms of IBD, including
visceral abdominal pain caused by colonic inflammation which is known to activate CB1 and CB2
receptors. (166) Diarrhea due to colitis has also been shown to be successfully managed with cannabis
due to its ability to inhibit intestinal secretion (158, 159, 167). Nausea and loss of appetite are two other
common symptoms IBD patient experience, both of which can be modulated with cannabis therapy. (168)
A questionnaire study found 50% of IBD patients reported any lifetime use and 15% reported current use
of cannabis. Use was most common in patients with previous abdominal surgeries and worse SIBDQ
scores. The most common reported side effects of cannabis in this study were dry mouth (67.6%),
drowsiness (68.0%), paranoia (32.0%), palpitations (30.5%), anxiety (23.5%), and memory loss (17.8%).
Another questionnaire study regarding personal use of cannabis in IBD patients discovered cannabis users
were more likely to have more severe disease and a higher risk for surgery although based on the design
of the study, causality is not able to be assessed. More severe IBD patients may simply be more likely to
use cannabis to treat their refractory disease. (169) However, there is also the risk that cannabis use can
cause worsening IBD symptoms and fibrosis or alternatively mask the severity of the symptoms allowing
the disease to progress.
One retrospective study found that 21 out of 30 CD patients had clinical improvement based upon
Harvey-Bradshaw Index after cannabis treatment and a decreased need for escalation of therapy and
surgery. (170) A prospective study of 21 medically refractory Crohn’s patients treated with cannabis twice
a day or placebo found a significant difference in clinical response defined as a decrease in CDAI score of
> 100 (p = 0.028). Complete remission (CDAI score < 150) was not significantly different between the
two groups, but subjects in the cannabis group reported improved sleep and appetite without any side
effects. (171) However, no objective markers such as endoscopic and laboratory values were reported in
these two studies.
The most important question is whether cannabis can ameliorate the inflammation associated with IBD.
Although there are no current answers to this question, there are ongoing clinical trials investigating this
topic. Currently, there is not enough evidence to recommend cannabis use for the treatment of IBD.
Further studies are needed to evaluate the appropriate formulation and route of administration that
cannabis may provide the most benefit with least adverse effects.
This summary of dietary supplemental therapies for the treatment of IBD brings to light the lack of robust
data in this field. Currently, vitamin D remains a hot topic in both the treatment and prevention of IBD.
However, with the data available, repletion of vitamin D to normal levels in IBD patients (30 – 100) is the
only recommendation that can be made. Fish oil supplementation has some promising data for colitis,
although cannot yet be recommended as a therapy due to lack of clear benefits and unknown toxicities.
VSL #3 is a recommended therapy for the prevention of recurrent pouchitis, but not for CD or UC at this
time. The other probiotics need larger, placebo-controlled trials before any recommendations can be
made. Prebiotics appear to be a basic component to maintain healthy gut flora, but do not yet have a role
in the treatment of IBD. While curcumin appears to be effective in the treatment of mild to moderate UC
and acts synergistically with mesalamine therapy, long term adverse events have not been well studied
and should be used with caution. Boswellia serrata and aloe vera do not have enough data to recommend
their use for the treatment of IBD at this time. Cannabis therapy cannot be recommended due to the
potential for serious adverse events and long term neurologic complications. There is encouraging data
that the therapeutic component of cannabis may be extracted, eliminating the harmful adverse effects.
Only with larger, placebo-controlled studies can the true efficacy of these therapies be determined.
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... On the other hand, in patients with UC, where the appearance of damaged lesions in the duodenum and small intestine is rare, vitamin deficiency is less frequent than in CD [64]. However, the absorption of vitamin D may be reduced due to interaction with 5-ASA preparations [65]. In patients with IBD, urinary excretion of calcium is enhanced during corticosteroid administration, increasing the risk of osteoporosis, and increased protein catabolism contributes to sarcopenia [65]. ...
... However, the absorption of vitamin D may be reduced due to interaction with 5-ASA preparations [65]. In patients with IBD, urinary excretion of calcium is enhanced during corticosteroid administration, increasing the risk of osteoporosis, and increased protein catabolism contributes to sarcopenia [65]. When IBD is active, the fat-soluble vitamins, vitamin A and vitamin E are decreased, as well as vitamin D [66]. ...
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Malnutrition is a major contributor to muscle loss and muscle dysfunction, known as sarcopenia. Malnutrition is common in patients with inflammatory bowel disease (IBD). IBD includes ulcerative colitis (UC) and Crohn’s disease (CD). The number of patients with IBD has recently been increasing. More severe malnutrition is often seen in CD compared to UC, probably due to CD affecting the main site of nutrient absorption, extensive mucosal lesions, fistulas, short bowel syndrome after resection, or obstruction of the gastrointestinal tract. A recent meta-analysis showed the high prevalence of sarcopenia in patients with IBD, and thus sarcopenia is a very important problem for IBD. Although IBD is more common in younger patients, sarcopenia can develop through a variety of mechanisms, including malnutrition, chronic inflammation, increased inflammatory status in adipose tissue, vitamin deficiency, and imbalance of the muscle–gut axis. In addition, sarcopenia has a negative impact on postoperative complications and hospital stay in patients with IBD. Appropriate intervention for sarcopenia may be important, in addition to clinical remission and endoscopic mucosal healing in patients with IBD. Much more attention will thus be paid to sarcopenia in patients with IBD. In this review, we outline IBD and sarcopenia, based on the current evidence.
... Due to abundant resources, notable therapeutic efficacy, and low toxicity, medicinal plants have recently become a promising approach for UC treatment (Li et al., 2022;Wei et al., 2021). Currently, in addition to pharmaceutical treatments, food supplements or nutritious natural plant extracts have significant antiinflammatory effects on UC (Parian & Limketkai, 2016;Radziszewska et al., 2022). Therefore, there is great potential to further explore food supplements for the treatment of UC. ...
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Ulcerative colitis (UC) is a digestive disease with a high incidence and is difficult to be cured due to its complex etiology. It has evidenced that intestinal barrier dysfunction plays a predominant role in UC. 20( S )‐protopanaxadiol saponins (PDS) isolated from Panax notoginseng possess anti‐inflammatory and antioxidative activities, suggesting its potential of treating UC. Herein, the therapeutic effects of PDS against UC and underlying mechanisms in the aspect of intestinal barrier dysfunction were investigated in vivo and in vitro. The results showed PDS had protective effects against dextran sulfate sodium–induced colitis, including attenuating weight loss, disease activity index score elevation, colon length shortening, and histological lesions. Additionally, PDS reduced the colonic activity of myeloperoxidase and the cytokine levels of TNF‐α, IL‐6, and IL‐1β, decreased MDA production, and elevated colonic activities of SOD and GSH‐Px in the colitis mice. The expressions of proteins related to tight junction (TJ), including ZO‐1, claudin‐5, occludin, caveolin‐1 (Cav‐1), and Nrf2 were downregulated, whereas that of Keap1 was upregulated after colitis induction. These changes were reversed by PDS. Cav‐1 expression was downregulated in lipopolysaccharides (LPS)‐ and H 2 O 2 ‐induced HCT116 cells, and the expressions of ZO‐1, claudin‐5, and occludin were suppressed in HCT116 cells stimulated by LPS and H 2 O 2 combined with Cav‐1 small interfering RNA transfection, which were ameliorated by PDS, suggesting PDS targeted Cav‐1 against intestinal barrier damage. Collectively, PDS alleviates inflammatory injury and oxidative stress by regulating the Nrf2/Keap1 pathway, contributing to targeting Cav‐1 against intestinal epithelial TJ proteins loss. It suggests PDS might be a promising therapeutic natural product for UC treatment.
... These oils alleviate the effect of colitis by reducing the excessive expression of cytokines caused by the intake of plant and fish oils (Yorulmaz et al., 2019;Tanideh et al., 2020). In mouse models, the use of natural dietary supplements such as yarrow oil (Mohamed et al., 2021), which alleviates colitis by regulating the NF-κB and PPAR-α pathways, has been reported (Parian and Limketkai, 2016). A previous study also reported that the acute inflammatory reaction in colitis models was alleviated by administering cotton seed oil, which restored the colon length and weight and reduced expression of inflammatory cytokines in the tissues (Park et al., 2019). ...
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Ulcerative colitis is caused by various external factors and is an inflammatory disease that causes decreased intestinal function. Tenebrio molitor larvae contain more than 30 % fat, and the fat component consists of 45 % oleic acid, 20 % linoleic acid and 20 % polyunsaturated fatty acids. In this study, after administering Tenebrio molitor larva oil (TMLO) in a dextran sodium sulphate (DSS)-induced ulcerative colitis mouse model, the pathological findings and inflammatory markers of colitis were analysed to assess whether a colitis mitigation effect was achieved. In the TMLO-administered group, the colon length increased, the spleen weight decreased, and the body weight increased compared with that in the DSS group. In addition, the disease activity index level decreased, the mRNA expression level of inflammatory cytokines in the colon decreased, and the myeloperoxidase activity level significantly decreased. Also, the activity of the NF-κB pathway involved in the regulation of the inflammatory response was lower in the TMLO group than in the DSS group. Taken together, these results suggest that TMLO suppresses occurrence of acute ulcerative colitis in the DSS mouse model. Therefore, TMLO has the potential to be developed as a health food for the prevention and treatment of ulcerative colitis.
Natural products we usually fed aid in preventing and treating various diseases, besides their nutritional functions. Recent clinical and preclinical studies have shown that consuming herbs and spices triggers beneficial biological effects. Boswellia serrata is a tree found mainly in dry areas in India, and traditional Arab, Ayurvedic, and Chinese medicine use its oleogum resin for medicinal purposes. Furthermore, there are several studies about its role as a nutraceutical and functional food. So, here we reviewed the beneficial effects of B. serrata on nutrition, as it presents antiinflammatory, anticancer, antidiabetic, and antioxidant properties, among others. The highlighting of B. serrata beneficial effects could offer a helpful direction to future studies and the development of a phytomedicine for the prevention and treatment of health conditions.
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Fenugreek also called as Trigonella foenum graecum, belong to Fabaceae family. It is one of the most common Indian spices that are particularly recognized for its culinary, medicinal, and aromatic properties. Fenugreek is more pronounced for its health-promising properties such as antiinflammatory, antiulcer, antidiabetic, and anticancer activities. Fenugreek is enriched with various chemical constituents that aids in enriching its nutraceutical properties. Its chemical constituents majorly composed of steroids, alkaloids, flavonoids, fibers, vitamin, and fatty acids. Fenugreek is enhancing human health by providing different bioactive compounds, antioxidant compounds, and hepatoprotective capacity. Fenugreek gel formation property aids in preventing antiulcer as studied with respect to some antiulcer drugs available like omeprazole. Fenugreek is one major kitchen ingredient that controls various metabolic diseases by its different nutraceutical properties. Based on the past evidences, the present review chapter aims to elaborate the nutraceutical properties of fenugreek.
Herbs, Spices and Their Roles in Nutraceuticals and Functional Foods gives an overview of the many pharmacological activities associated with herbs and spices, including detailed coverage on their mechanisms and formulations for the food industry. Chapters focus on key ingredients such as Curcuma longa, Piper Nigrum and Trigonella foenum-graecum, with contributors across the globe providing the latest research and advances for each. This is an essential read for scientists who want to understand the fundamental mechanisms behind the bioactive compounds within herbs and spices. The numerous phytochemicals present in plant extracts have multiple pharmacological activities so there is extensive research into new bioactive compounds. The pharmacological activities of herbs and spices have been thoroughly investigated, and it is crucial that the latest research is organized into a comprehensive resource.
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Objective To investigate the preventive effects of plant oils with different linoleic acid/alpha-linolenic acid (LA/ALA) ratios against colitis symptoms, and dysbiosis of gut microbiota in acute colitis mouse model. Methods Sixty male C57BL/6 mice were assigned into six groups ( n = 10): three groups were fed low-fat diets with low, medium, and high LA/ALA ratios; and three groups were fed with high-fat diets with low, medium, and high LA/ALA ratios. After 3 months of diet, the mice were exposed to dextran sodium sulfate solution to induce acute colitis. The severity of colitis was estimated by disease activity index (DAI) and histopathological examination. 16S rRNA gene sequencing was used for the analysis of gut microbiota. Results Plant oils with a lower LA/ALA ratio showed higher alleviating effects on the symptoms of colitis, which were accompanied by the better prebiotic characteristics manifested as effectively inhibiting the abnormal expansion of phylum Proteobacteria and genus Escherichia-Shigella in the gut microbiota of colitis mouse models. Conclusion A potential IBD prevention strategy of reducing the LA/ALA ratio in the daily consumed plant oils was proposed in this study. Furthermore, based on the optimized LA/ALA ratio, this preventive effect might not be weakened by the high intake of plant oils.
Many microorganisms populate the gastrointestinal tract (GIT) and changes in gut microbiota can interfere with health maintenance or the development of the disease process. This chapter compiles experimental and clinical findings using probiotics to treat or prevent the main pathologies affecting the GIT. The pieces of evidence point to the beneficial effects of probiotics in diseases such as mucositis, gastroesophageal reflux disease, gastritis, chronic constipation, inflammatory bowel diseases, and irritable bowel syndrome. Despite the promising studies demonstrating the actions of probiotics in GIT diseases, their use in clinical practice is still limited, as it is necessary to fully attest to their safety and efficacy in specific gastrointestinal pathologies.
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With the increasing incidence of ulcerative colitis (UC) in China, Chinese medicinal herbs or relatively active compounds are widely applied in treating UC. These medicines may be combined with other therapeutic agents such as vitamin D3. Nevertheless, the efficacy of these combinations for UC is unclear. Geniposide is an active component in many Chinese herbal medicines. It could ameliorate dextran sulfate sodium (DSS)–induced colitis in mice. This study was designed to determine the efficacy and mechanism of the single use and combination of geniposide and vitamin D3 on a mouse model of acute colitis. Data showed that a single administration of geniposide (2 mg/kg) or vitamin D3 (4 IU/day) could significantly improve the symptoms of UC and relieve colon damage. Geniposide and vitamin D could significantly decrease the levels of TNF-α and IL-6 in serum and colon, and increase the level of IL-10 in the colon. However, the combined treatment of geniposide (2 mg/kg) and vitamin D3 (4 IU/day) exerted less beneficial effects on UC in mice, indicating by less improvement of UC symptoms, colon damage, and inflammatory infiltration. The combination only downregulated the level of TNF-α in serum and IL-6 in the colon. Our data further demonstrated that geniposide could inhibit the activation of p38 MAPK and then restrict the vitamin D receptor signaling stimulated by vitamin D3. These results implied that the combination of geniposide and vitamin D3 might not be an ideal combined treatment for acute colitis, and the combination of vitamin D supplementary and geniposide (or herbal medicines rich in geniposide) need more evaluation before being applied to treat UC in clinic.
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Inflammatory bowel disease Inflammatory bowel disease (IBD) is an im-munological disorder, encompassing Crohn's disease and ulcerative colitis, which are characterized by chronic intes-tinal inflammation targeted at harmless commensal bacteria and food antigens. Although the aetiology of IBD remains un-clear, environmental factors in susceptible individuals appear to trigger immunolo-gical responses that inflame and damage tissues of the digestive tract. Prevalence of IBD is markedly higher in industrialized and affluent countries [1] (see Fig. 1). Evidence of a major underlying role for genetic pre-disposition to IBD raises the likelihood that the origins of disease and the susceptibility of the current human 'immunome' is the evolutionary consequence of marked and prolonged genetic selective pressure exerted by infectious pathogens [3]. Evolutionary perspectives The Hygiene Hypothesis suggests that increasing allergic and autoimmune dis-eases are related to improved hygiene, e.g. the absence of helminth infections in more developed countries [1]. Notably, allergic diseases are less common where parasites are rife, while the elimination of helminths can increase the atopic response to aller-gens. Our human ancestors would have been exposed to such infections causing, over evolutionary time, the human immune system to be optimally calibrated for their presence [3]. In helminth-free settings, our immune system may be maladapted and, where free of the dampening effect of helminths, may over-react to harmless antigens. Multiple studies have revealed that helminths sup-press a broad range of inflammatory responses [4], which may explain why ex-posure to helminths such as Trichuris suis (whipworm) has been reported to be well tolerated by patients and improve IBD with-out any overt side-effects in an open label trial [5, 6]. These therapies are now being evaluated in double-blind clinical trials.