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Astaxanthin and Gastric Health

Lowering Gastric Inflammation

10-days of treatment (in vivo), and also inhibit H. pylori growth (in
vitro). The mice treated with astaxanthin (10 mg/kg body weight) had
the same effect as vitamin C (400 mg/Kg) which significantly lowered
gastric inflammation and lipid peroxidation (Figure 4) compared to
Astaxanthin for Dyspepsia and Helicobacter infected control mice; which continued to develop severe gastritis.
pylori
Dyspepsia is the general term Figure 1. IL-4 release of splenocytes after restimulation with
given to a variety of digestive H. pylori sonicate (Bennedsen et al., 1999)
*p<0.001
problems localized in the upper 120

abdominal region. Typical 100

symptoms for example include 80


Helicobacter Pylori
stomach pain, gas, acid-reflux or

IL- 4 pg/ml
60

bloating. Dyspepsia is like the stomach version of the irritable bowel 40

syndrome and its symptoms may appear at any age or to any gender. The 20 *
medical approach to dyspepsia involves looking for treatable causes and 0

addressing them if identified. Failing that, doctors suggest treatments by -20


Infected Infected + treated Uninfected
trial-and-error. The problem associated with this non-standardized
approach involves drugs that may not work, may cause side effects and Astaxanthin improved the cytokine IL-4 response (Th2 T-cell) to the presence of H.
pylori (in vitro).
exacerbate the patient’s condition brought on by stressful attempts to cure
symptoms.
Figure 2. Gastric inflammation (antrum + corpus) (Bennedsen et al., 1999)
*p=0.01
To understand the benefits of astaxanthin in dyspepsia, it is necessary to 2.4
2.2
categorize specific types; most common forms are either non-ulcer
Gastric inflammation score

2
dyspepsia or gastric dyspepsia. Non-ulcer dyspepsia problems usually do 1.8

not have an identifiable cause, but fortunately, for most cases it is 1.6
1.4
non-disease related and therefore temporary. On the other hand, gastric 1.2 *
type dyspepsia is more severe and linked to identifiable causes. For 1

example, the bacterial infection of Helicobacter pylori is a commonly 0.8


0.6
known cause. Pathological symptoms of H.pylori infection include high 0.4
Infected Infected + treated Uninfected
levels of oxidative stress and inflammation in the stomach lining and
symptoms like gastric pain and acid reflux., H.pylori can contribute to Astaxanthin reduced gastric inflammation in Helicobacter pylori infected mice.

mild and severe kinds of symptoms, but on the other hand, people who
Figure 3. Bacterial load (antrum + corpus) (Bennedsen et al., 1999)
are H.pylori positive can remain asymptomatic whereas others may
*p<0.02
develop into clinical problems. It is still unclear what triggers the severe 1200

form of infection and how the bacteria is passed on, but scientists 1000

800
suggested using strong antioxidants like astaxanthin for therapy and better
CFU

600
long term protection.
400 *
200

Helicobacter pylori in Gastric Dyspepsia -200


Infected Infected + treated Uninfected

This Gram-negative bacterium is present in approximately half of the Astaxanthin reduced Helicobacter pylori colonization of the stomach of infected mice.
world population, and typically resides in the human gastric epithelium
(stomach lining). H.pylori infection is generally acknowledged as the Figure 4. Amount of lipid peroxidation products (MDA and
4-hydroxyalkenals) during H. pylori infection (Wang et al., 2000)
main cause for type B gastritis, peptic ulcer disease and gastric cancer.
50
Lipid peroxidantation (µmol/g tissue)

The pathogenesis of this infection is partly due to the immunological


response as shown by Bennedsen et al., (1999). Astaxanthin (200 40

mg/kg body weight) fed to H.pylori infected mice for 10 days exhibited
30
signs of improved immune system. Normally, the T-helper1 (Th1)
response exacerbates inflammation and epithelial cell damage due to 20

infection, but the astaxanthin treated mice responded with a mixed 10

Th1/Th2-response (Figure 1), which lowered gastric inflammation


0
(Figure 2) and bacterial loads (Figure 3). Furthermore, the findings by Normal HP control HP + Meal HP + Algal meal HP + Vitamin C
control control (10mg/kg) (400mg/kg)
Wang et al., (2000) also supported the idea that a diet supplemented
Lipid peroxidation levels lowered in H. pylori infected mice after treatment with
with astaxanthin or vitamin C in mice lowered inflammation after astaxanthin or Vitamin C.
The success of astaxanthin in dyspepsia animal models prompted Figure 6. Reflux-syndrome
further prospective human studies. In 1999, the first clinical study Astaxanthin (40mg) Astaxanthin (16mg) Placebo * p<0.05
Mean GSRS score
performed in collaboration with the Centre for Digestive Diseases, 3

Australia, involved 10 H.pylori positive subjects (non-ulcer) with typical


2,5
dyspeptic symptoms such as heartburn and gastric pain, were each
treated with 40 mg daily dose of astaxanthin for 21 days. 10 clinical 2

parameters assessed the efficacy before and after the treatment period. 1,5
*
The gastric pain, heartburn and total clinical symptoms results showed
1
a significant drop of 66%, 78% and 52% drop respectively (Figure 5).
Furthermore, follow-up checks 27 days after the cessation of
Baseline 4 weeks later
astaxanthin intake (a total of 49 days from day 0), showed that the
Reduced reflux-syndrome score of non-ulcer dyspepsia patients treated with 16 mg
dyspeptic symptoms remained low (Lignell et al., 1999). In summary, and 40 mg astaxanthin.
astaxanthin effectively controlled the dyspepsia symptoms, and H.pylori
eradication trend was observed, but not significant. Outlook
There are considerable overlaps in a number of gastrointestinal
Figure 5. Total Clinical Symptoms (Lignell et al., 1999)
disorders that may be treatable with conventional medicine, but what if
100
it does not work? In that case, astaxanthin may be useful, particularly
90
91 against H.pylori positive gastritis and non-ulcer dyspepsia acid reflux.
80
70 The mechanisms of action include the following: decreasing oxidative
60
stress by astaxanthin’s potent antioxidant property; controlling bacterial
50
40
infection by shifting the immune response; and alleviating dyspeptic
44
30 38 symptoms by retarding inflammation. Furthermore, these results infer
20
that acid reflux in connection with either H.pylori positive or negative
10
0
conditions can still expect improvements with astaxanthin.
Day0 Day22 Day49

Intake of Astaxanthin for 21 days


Astaxanthin reduced total grade of clinical symptoms in H. pylori positive
non-ulcer dyspeptic subjects after 21 days. Low symptom score continued even up References
to 28 days after treatment ceased.
1. Bennedsen M, Wang X, Willen R. Treatment of H. pylori infected
mice with antioxidant astaxanthin reduces gastric inflammation,
Reflux in Non-Ulcer Dyspepsia bacterial load and modulates cytokine release by splenocytes.
Immunol Lett. 1999. 70: 185-189.
Approximately one in four people experience
2. Kupcinskas L, Lafolie P, Lignell A, Kiudelis G, Jonaitis L, Adamonis
dyspepsia at some time that are linked to K, Andersen LP, Wadstrom T. Ef?cacy of the natural antioxidant
common causes such as food types, stress, astaxanthin in the treatment of functional dyspepsia in patients with
or without Helicobacter pylori infection: A prospective, randomized,
stomach ulcers, or acid reflux (stomach acid
double blind, and placebo-controlled study. Phytomedicine 2008.
backs-up into the esophagus). If the exact 15: 391–399.
causes of non-ulcer dyspepsia are unknown, 3. Lignell A, Surace R, Bottiger P, Borody TJ. Symptom improvement in
there are no standardized treatments that Helicobacter pylori positive non-ulcer dyspeptic patient after
exist to effectively treat the patient. The treatment with the carotenoid astaxanthin. In: 12th International
Carotenoid Symposium, Cairns, Australia, 18-23 July 1999.
usual procedure involves the problematic
4. Wang X, Willen R, Wadstrom T. Astaxanthin rich algal meal and
remedies of acid blocking medicines, vitamin C inhibit Helicobacter pylori infection in BALB/cA mice.
painkillers or antibiotics. However, drug treatment faces problems with Antimicrob Agents Chemother. 2000. 44: 2452-2457.
increasing antibiotic resistant bacteria and carries increased risk of
damage to the stomach. Therefore, clinically proven non-drug
treatments are becoming more attractive to physicians and patients.
H.pylori & Dyspepsia Patents
Astaxanthin efficacy in non-ulcer dyspepsia was demonstrated in a WO98/37874 and WO00/23064.
randomized double-blind placebo controlled study involving 131
patients complaining of non-ulcer dyspepsia. This collaborative trial
conducted by the Kaunas University Hospital, Lithuania; Rigshospitalet,
Copenhagen; University of Lund and the Karolinska Institute, Sweden
demonstrated that 40 mg astaxanthin treatment up to 4 weeks
significantly reduced reflux compared to the 16 mg (P<0.05) or
placebo (P<0.05) groups (Figure 6). Although there was a strong
placebo effect, other improved trends included reduced gastric pain and
abdominal pain (Kupcinskas et al., 2008) .

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