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Astaxanthin and Hypertension

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					                        Astaxanthin and Hypertension
Astaxanthin Reduces Hypertension                                      in SHR (Figure 2). Furthermore, astaxanthin had no effect on the
                                                                      normal blood pressure in healthy rats.
Epidemiological and clinical data suggest that dietary
carotenoids such as astaxanthin may protect against                   Interestingly, the authors reported a 50% reduction of incidence
cardiovascular disease (CVD) which includes hypertension. This        of stroke in the treated (50 mg/kg/day) SHR-SP group compared
condition is associated with blood vessel dysfunction, altered        to the control group after 14 days. (Hussein et al., 2005a).
contractility and tone; mediated by relaxant (nitric oxide NO;
prostacyclin) and constrictor factors (thromboxane; endothelin)       In addition, astaxanthin treated mice also showed significant
in the blood. Furthermore, blood flow properties serve an             neuroprotective effects at relatively high doses by preventing
                                     important role in the            the ischemia-induced impairment of spatial memory in mice
                                     pathological complications       negotiating a water maze (Hussein et al., 2005a). This effect is
                                     seen in atherosclerosis and      suggested to be due to the significant antioxidant property of
                                     coronary heart disease.          astaxanthin on ischemia-induced free radicals and their
                                     Research presented here          consequent pathological cerebral and neural effects. The
                                     suggests that astaxanthin        neuronal protection of astaxanthin during ischemia was also
                                     may be useful as part of an      confirmed in an earlier study by Kudo et al., 2001.
                                     antioxidant therapy to
                                     alleviate hypertension           Figure 2. Astaxanthin (5 mg/kg/day) treated SHR reduced mean
                                     (Figure 1).                      blood pressure. ***p<0.001. Hussein et al., 2005b.
                                                                                                       180
                                                                                                       175
                                                                          Mean blood pressure (mmHg)




Figure 1. Mechanisms by which Astaxanthin reduces hypertension                                         170
                                                                                                       165
                   Maintains vessel integrity                                                          160                                           ***
                                                                                                       155                             ***
                                                                                                                                                                  ***
                                                                                                       150                                                                     ***
                                                                                                       145
                                                                                                                          Olive oil (1ml/kg),p.o.(8)                                        ***
                                                                                                       140
                                                                                                                          Astaxanthin (5mg/kg),p.o.(8)
                                                                                                       135
                                                                                                       130
                                                                                                             0        1     2           3            4             5           6         7

                    anti-hypertension                                                                                              Treatment period(week)




                                                                      Mechanism of Anti-hypertension
   Restoration of vessel              Improved blood rheology
  dilation & constriction                                             The antihypertensive mechanism may be in part explained by
                                                                      the changes of vascular reactivity and hemorheology.


Reduction of Arterial Blood Pressure                                  Microchannel Array Flow Analysis (MC-FAN) measured a
                                                                      significant increase of blood flow of 11% (Figure 3) in the
An early study involving a composition of carotenoids have been       astaxanthin treated group (N=6-7, p<0.05). Although plasma
used against hypertension or high blood pressure (BP), but            fluidity is largely influenced by fibrinogen, in this study, the
Hussein et al., (2005a) published the first study involving           fibrinogen levels did not change and therefore, the improved
astaxanthin with spontaneously hypertensive rats (SHR) and            deformation and reduced blood aggregation are the likely
stroke prone (SHR-SP). This study investigated the effects of         mechanisms (Hussein et al., 2005b). This is supported by
astaxanthin on the aortic vessel blood pressure (BP) in relation to   Miyawaki et al., (2005) who also used the MC-FAN to demonstrate
endothelium and nitric oxide (NO) to elucidate mechanism and
response. The arterial BP in
hypertensive rats (N=5-6,                                             Figure 3. Astaxanthin (5 mg/kg/day) treated SHR improved
p<0.05) fell by almost 10% when                                       blood flow tested by MC-FAN. * p<0.05: ** p<0.01 vs. control.
                                                                      Hussein et al., 2005b.
they were treated with 50 mg
                                                                                                       70
astaxanthin/kg/day for two
                                                                                                       60
weeks. Long term
                                                                                                       50                                                                               *
supplementation in SHR-SP rats
                                                                                                       40
                                                                       Time (sec)




revealed that 5 mg/kg/day also                                                                                                                                          **
                                                                                                       30
had the same effect as 50                                                                                                                       **
                                                                                                       20
mg/kg/day (8-9% BP reduction, N=5, p<0.001). At the same time,                                                             **                            Olive oil (1ml/kg),p.o.(6)
                                                                                                       10                                                Astaxanthin (5mg/kg),p.o.(7)
the control group BP increased by 8% at week 5. Two further                                             0
studies (N=5-8) by Hussein et al., (2005b and 2006) confirmed                                                    20        40                   60                     80               100
                                                                                                                                             Volume (µl)
this observation by reducing BP almost 16% (p<0.001) at 7 weeks
the significant improvement of blood flow (N=10, p<0.05) in                             Figure 6. A) Coronary artery wall is thinner and lumen is wider in
humans treated with 6 mg astaxanthin for 10 days (Figure 4).                            astaxanthin treated rats. B) Elastin bands are also fewer in
                                                                                        number and smoother compared to the control groups. Hussein
                                                                                        et al., 2006.
A systematic investigation in both relaxant and constrictor                              A. Arterial wall of control and astaxanthin groups. Staining: hematoxylin-eosin.
responses revealed that astaxanthin can restore the NO                                   Magnification: 20x
dependent relaxation and sensitivity to constriction mechanisms
(Figure 5). Astaxanthin
reduced sensitivity to
angiotensin II (AngII)
which is involved in
vessel contraction, and
scavenged ROS which                                                                                       Control                             Astaxanthin

would normally hinder
                                                                                         B. Sections of the aorta of control and astaxanthin groups showing elastin
nitric oxide (NO)                                                                        bands. Staining: Verhoff ’s. Magnification: 40x.
dependent dilation
(Hussein et al., 2005b,
2006a, 2006b).

Astaxanthin treatment
also maintained the                                                                                       Control                             Astaxanthin
structural composition of the vessel wall structure. Hypertension
normally produces thick walled vessels which alter stiffness and
internal volume; thereby reducing volume of blood flow and
                                                                                        Outlook
increasing pressure. Astaxanthin treated rats were protected                            The oxidative status and physiological condition during
from such structural changes (Figure 6) as seen in the reduction                        hypertension are successfully mediated by astaxanthin. The
of the number of branched elastin bands (p<0.001) and                                   mechanisms of action include improved blood rheology,
improved vessel wall to lumen thickness ratio (p<0.01). Li et al.,                      modulation of constrictor and dilator factors and blood vessel
(2004) substantiated the same structural preservation effect after                      remodelling. Although, these findings are based on spontaneous
treating hyperlipidemic rabbits (WHHL) with astaxanthin. The                            hypertensive rat models, these serve as a solid basis for
                                                                                        extending the hypothesis to human clinical trials.
intactness of the internal elastic membranes of aortic segments
was an important gauge of atheroma.
                                                                                        References
                                                                                        1. Hussein G., et al., 2006b. Astaxanthin, a Carotenoid with Potential in
Figure 4. Astaxanthin (6 mg/day) supplementation for 10 days                            Human Health and Nutrition. J. Nat. Prod. 69(3):443 – 449.
improves blood flow in humans as tested by MC-FAN. *p<0.01
vs. start; #p<0.05 vs control. Miyawaki et al., 2005.                                   2. Hussein G., et al., 2006a. Antihypertensive potential and
                                                                                        mechanism of action of astaxanthin: III. Antioxidant and
                                      60                                                histopathological effects in spontaneously hypertensive rats. Biol.
                                                                    *
                                                                                        Pharm. Bull. 29(4):684-688.
     Blood Transit Time (Sec/100µl)




                                                                                        3. Hussein G., et al., 2005b. Antihypertensive potential and
                                      50                                                mechanism of action of astaxanthin II. Vascular reactivity and
                                                                            #
                                                                                        hemorheology in spontaneously hypertensive rats. Biol. Pharm. Bull.
                                                                                        28(6):967-971.
                                                                                        4. Hussein G., et al., 2005a. Antihypertensive and neuroprotective
                                      40                                                effects of astaxanthin in experimental animals. Biol. Pharm. Bull.
                                                                                        28(1):47-52.
                                                                                        5. Miyawaki H., et al., 2005. Effects of astaxanthin on human blood
                                      30                                                rheology. J. Clin. Thera. Med. 21(4):421-429.
                                           Before                   After               6. Li W., et al., 2004. Alpha-tocopherol and astaxanthin decrease
                                                                                        macrophage infiltration, apoptosis and vulnerability in atheroma of
                                                                                        hyperlipidaemic rabbits. J. Mol. Cell. Cardio. 37:969-978.
Figure 5. Astaxanthin increases relaxant and reduces constrictor
mechanisms to help reduce blood pressure in SHR.                                        7. Kudo Y., et al., 2001. Effects of astaxanthin brain damages due to
                                                                                        ischemia. Presented at the Annual Carotenoid Conference, 2001,
                                                                                        Toyama.
                                              Astaxanthin



   Reduces sensitivity to AngII                            Removes ROS (superoxide)




    Lowers vessel contraction                                Ameliorates NO dependent
                                                                  vessel dilation



                                           Reduces Blood Pressure




                                                                                                                                                       AX_Hypertension_MAR28.07

				
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