The Effects of Astaxanthin - Type 2 Diabetes

 

 

Draining the World Wealth

Diabetes mellitus is a worldwide epidemic that is critically linked to prevalence of obesity. More than 220 million people have diabetes and by the year 2030 the figures are expected to grow to 360 million. The diabetes is aggressively growing in both emerging and developed country. According to WHO, the Asian continent has over 90 million people suffering from diabetes – India (40 million) China (29 million); Indonesia (13 million) and Japan (7 million). The prevalence of diabetic patients remains pervasive in USA (22 million), Brazil (6 million), Pakistan (8 million); Russia (6 million); Italy (5 million) and Turkey (4 million). Even in the African region over 10 million people suffer from diabetes, especially in Nigeria where it is expected to reach 5 million within the year 2030.
Diabetic complications lead to heart disease (approximately 65% of death amongst diabetics), blindness, kidney failure and amputations. As a result, the indirect and direct medical expenditure of diabetics represent almost 5 times that of a non-diabetic.

Type 2 Diabetes: A Preventable Disease

 

In most cases, diabetes is treated with medication, although about 20% of diabetics may be managed by lifestyle changes. This means that even if we cannot change the genetic influences, fortunately, for most of us diabetes is preventable; for example, making dietary changes, taking nutritional supplements and exercising. To highlight this, people in high risk groups who achieve a 5-7% cut in body weight will reduce risk of developing diabetes approximately 58% across all age and ethnic groups.
While the debate between the contributory effects of carbohydrate and fat intake continues unabated, research reveals a strong link between foods with high glycemic index and prevalence of type 2 diabetes. Excess blood glucose needs to be converted by insulin (produced by the pancreas ß-cells) into glycogen stores, however, when glycogen stores are full, glucose is converted into fat. Over time, the body’s cells may eventually become desensitized to insulin making it necessary to produce more insulin to achieve the same affect. It is this process that would eventually lead to a state known as hyperinsulinaemic state. As a result, the body looses its ability to control high blood glucose levels (hyperglycemia) that could result in toxic conditions and promote further complications such as kidney failure.

New Evidences Emerging from Human Studies

In an anti-aging study conducted by Iwabayashi et al., (2009), 20 female volunteers with increased oxidative stress burden ingested 12 mg/day of astaxanthin for 8 weeks. Results evidenced a significant decrease of diabetes-related parameters that collectively predict trends in diabetes development. Firstly, astaxanthin reduced cortisol by 23 percent.

Astaxanthin Retards Glucose Toxicity and Kidney Damage

Astaxanthin displayed positive effects in a type 2 diabetic mouse model in that it reduced the disease progression by retarding glucose toxicity and kidney damage. This has profound implications for people who belong to high risk groups, display pre-diabetic conditions (impaired fasting glucose or impaired glucose tolerance) or want to manage advanced diabetic kidney problems (nephropathy).
Studies suggested that reactive oxygen species (ROS) induced by hyperglycemia contributes to the onset of Diabetes mellitus and its complications. Non-enzymatic glycosylation of proteins and mitochondria, prevalent in diabetic conditions, is a major source of ROS. For example, pancreatic ß-cells kept in high glucose concentrations show presence of advanced glycosylation products, a source of ROS, which cause the following: i) reduction of insulin expression and ii) induction of cell death (apoptosis). ß–cells are especially vulnerable to ROS because these cells are inherently low in antioxidant status and therefore, requires long term protection. A recent study demonstrated that antioxidants (N-acetyl-L-cysteine, vitamins C and E) exerted beneficial effects in diabetic conditions such as preservation of ß-cell function, so it is likely that a more potent antioxidant such as astaxanthin can do the same or better.
In another study conducted by Preuss et al. (2009), 12 rats fed with 25mg/kg of astaxanthin show a significant decrease in insulin resistance by 13.5%.

Modulation of Glucose Toxicity

Uchiyama et al., 2002 demonstrated in obese diabetes type 2 mouse model that astaxanthin preserved pancreatic ß -cell dysfunction against oxidative damage. Treated mice received 1 mg astaxanthin/day at 6 weeks of age and then tests performed at 6, 12 and 18 weeks. Observations of astaxanthin treated mice (N=8) included: i) significantly reduced fasting glucose sugar levels at 12.

Figure 1. Astaxanthin improved the glucose levels in the Intraperitoneally Glucose Tolerance Test (IPGT) in diabetic mouse model (Uchiyama et al., 2002)

Figure 2. Astaxanthin preserved insulin sensitivity in the diabetic mouse model (Uchiyama et al., 2002)

Figure 3. Astaxanthin protected kidney function measured by urinary albumin protein loss (Naito et al., 2004) 

 

Prevention of Diabetic Nephropathy

As well as substantiating observations by Uchiyama et al., Naito demonstrated that astaxanthin treated type 2 diabetic mice which normally shows renal insufficiency at 16 weeks of age in fact exhibited 67% less urinary albumin loss.

Figure 4. Astaxanthin reduced the amount of DNA damage indicated by urinary 8-OHdG levels (Naito et al., 2004) 

 

Figure 5. Astaxanthin preserved the relative mesangial area.

 
Earlier it was unclear how astaxanthin could ameliorate the progression of diabetic nephropathy, but new evidence revealed additional information in the mechanism of action. Naito et al., (2006) examined changes in the gene expression profile of glomerular cells in diabetic mouse model during the early phase of diabetic nephropathy. The mitochondrial oxidative phosphorylation pathway was most significantly affected by high-glucose concentration (mediated via reactive oxygen species). Long term treatment with astaxanthin significantly modulated genes associated with oxidative phosphorylation, oxidative stress and the TGF-ß-collagen synthesis system.

Manabe et al., 2007 went further and analyzed normal human mesangial cells (NHMC) exposed to high glucose concentrations. In the presence of astaxanthin, it significantly suppressed ROS production (Figure 6) and inhibited nuclear translocation and activation of NF-ĸB (Figure 7) in the mitochondria of NHMC. Furthermore, this was the first time to detect astaxanthin in the mitochondrial membrane (Table 1) and its presence also suppressed ROS attack on membrane proteins.

Figure 6. Astaxanthin reduced ROS production in NHMC-mitochondria exposed to high glucose (Manabe et al., 2007) 

   

Top left panel: mitochondria as green fluorescence, Top right panel: ROS as red fluorescence; Bottom right panel: Merged picture as yellow fluorescence.

Figure 7. Astaxanthin suppressed high-glucose induced nuclear translocation and activation of NF-ĸB (Manabe et al., 2007) 

 

Table 1. Astaxanthin content in NHMC mitochondria expressed as percentage of total astaxanthin added. 

Mean of 3 samples. (Manabe et al., 2007)

Outlook

Although clinical trials involving antioxidants in humans have only recently begun, these preliminary results concluded that strong antioxidant supplementation may improve type 2 diabetic control and inhibit progressive renal damage by circumventing the effects of glycation-mediated ROS under hyperglycemic conditions. Astaxanthin improved pancreas function, insulin sensitivity, reduced kidney damage and glucose toxicity in diabetic mouse models. New techniques by gene chip analysis and fluorescence imaging revealed further details of mechanism and site of protection by astaxanthin. Further research and clinical studies are still required. However, it is reasonable to suggest that astaxanthin may be useful as part of a nutrigenomic strategy for type 2 diabetes and diabetic nephropathy.

References

1. Forefront (Summer/Fall) 2005, American Diabetes Association.
2. Functional Foods & Nutraceuticals June 2004. "The dietary solution to diabetes."
3. HSR Health Supplement Retailer July 2004. "Fighting Diabetes the natural way."
4. Iwabayashi M, Fujioka N, Nomoto K, Miyazaki R, Takahashi H, Hibino S, Takahashi Y, Nishikawa K, Nishida M, Yonei Y. (2009). Efficacy and safety of eight-week treatment with astaxanthin in individuals screened for increased oxidative stress burden. J. Anti Aging Med., 6 (4):15-21.
5. Manabe E, Handa O, Naito Y, Mizushima K, Akagiri S, Adachi S, Takagi T, Kokura S, Maoka T, Yoshikawa T. (2008). Astaxanthin protects mesangial cells from hyperglycemia-induced oxidative signaling. J. Cellular Biochem. 103 (6):1925-37.
6. Naito Y, Uchiyama K, Aoi W, Hasegawa G, Nakamura N, Yoshida N, Maoka T, Takahashi J, Yoshikawa T. (2004) Prevention of diabetic nephropathy by treatment with astaxanthin in diabetic db/db mice. BioFactors 20:49-59. Nutritional Outlook April. "Fighting Diabetes"
7. Naito Y, Uchiyama K, Mizushima K, Kuroda M, Akagiri S, Takagi T, Handa O, Kokura S, Yoshida N, Ichikawa H, Takahashi J, Yoshikawa T. (2006). Microarray profiling of gene expression patterns in glomerular cells of astaxanthin-treated diabetic mice: a nutrigenomic approach. Int. J. Mol. Med.,18:685-695.
8. Preuss H, Echard B, Bagchi D, Perricone VN, Yamashita E. (2009). Astaxanthin lowers blood pressure and lessens the activity of the renin-angiotensin system in Zucker Fatty Rats. J. Funct. Foods, I:13-22.
9. The Global Diabetes Community. http://www.diabetes.co.uk. Article retrieved on June 8th, 2010.
10. Uchiyama K, Naito Y, Hasegawa G, Nakamura N, Takahashi J, Yoshikawa T. (2002). Astaxanthin Protects β–cells against glucose toxicity in diabetic db/db mice. Redox Rep., 7(5):290-293.

CCRES special thanks to 

  Mr. Mitsunori Nishida, 

 
President of Corporate Fuji Chemical Industry Co., Ltd.

Croatian Center of Renewable Energy Sources (CCRES) 

CCRES Algae Project Q&A

 CCRES ALGAE

CCRES Algae Project
Q&A

See answers to common questions about growing algae for biofuel production.

    Algae’s potential
    What makes algae a better alternative fuel feedstock than cellulosic feedstocks, such as switchgrass or miscanthus?
    What transportation fuels can algae produce?
    How much fuel can algae produce?
    Where could this type of algae grow?
    What can you do with material derived from algae production not used for fuel?

    Economics
    How much would a gallon of algae-based transportation fuel cost if it were available at a service station today?
    What can accelerate the commercial availability of algae biofuel?

    Environment
    How will algae-based transportation fuels impact greenhouse gas emissions?
    Is the process capable of being replicated at the local level to increase energy efficiency and promote low-energy overhead?

    Security
    Can algae-based fuels be used in developing countries to help them bypass fossil fuel dependence?

CCRES ALGAE

Q: What makes algae a better alternative fuel feedstock than cellulosic feedstocks, such as switchgrass or miscanthus?

    A: Large-scale production of resource-intensive plants, like switchgrass or miscanthus, requires a substantial amount of fertile land, fresh water, and petroleum-based fertilizer to grow. The fuel derived is ethanol, a lower-energy fuel not compatible with the infrastructure now used to transport, refine, and deliver liquid fuels, like gasoline and diesel.

    Conversely, algae can produce hydrocarbons capable of being converted directly into actual gasoline or diesel fuel, which can be transported and delivered to market using the existing refinery infrastructure.


Q: What transportation fuels can algae produce?
    A: Algae produce a variety of fuel and fuel precursor molecules, including triglycerides and fatty acids that can be converted to biodiesel, as well as lipids and isoprenoids that can be directly converted to actual gasoline and traditional diesel fuel. Algae can also be used to produce hydrogen or biomass, which can then be digested into methane.

Q: How much fuel can algae produce?

    A: The United States consumes 140 billion gallons per year of liquid fuel. Algae can produce 3,000 gallons of liquid fuel per acre in a year, so it would take 45 million acres of algae to provide 100% of our liquid fuel requirements.

    For comparison, in 2008 the United States had 90 million acres of corn and 67 million acres of soybeans in production. So growing 45 million acres of algae, while challenging, is certainly possible.


Q: Where could this type of algae grow?

    A: Algae perform best under consistent warm temperatures between 20 and 30 degrees. Climates with plenty of sunshine offer optimal conditions. Ideal Croatian locations include many of the southern and southwestern areas, such as Dalmatia,(including Dalmatian hinterland ).

CCRES ALGAE

 
Q: What can you do with material derived from algae production not used for fuel?

    A: Production of 140 billion gallons of fuel from algae would also yield about 1 trillion pounds of protein. Since algae-produced protein is very high quality, this protein could be used to feed livestock, chicken, or fish. Presently, all livestock in this country consume about 770 billion pounds of protein per year.


Q: How much would a gallon of algae-based transportation fuel cost if it were available at a service station today?

    A: Today, the cost would be relatively expensive. Additional investment in research is needed to further refine and enhance the algae strains that generate such fuels. Also, more infrastructure needs to be developed to achieve the necessary economies of scale that will come with large-scale commercial production. Once overall efficiency increases, the cost of producing a gallon of gasoline from algae will dramatically reduce.


Q: What can accelerate the commercial availability of algae biofuel?

    A: As viable and potentially transformational as algae-based transportation fuels have already proven, we need a much better knowledge base on algae at the microbial level. We also need to build on this platform to develop the tools and train the next generation of scientists that will help usher in the age of accessible, affordable, and sustainable fuels made from algae. That is a central component of the Croatian Center for Algae Biofuels (CCRES Algae Project).

CCRES ALGAE

Q: How will algae-based transportation fuels impact greenhouse gas emissions?

    A: Production of alternative transportation fuels from algae will help reduce the amount of CO2 in the environment. Algae provide a carbon-neutral fuel because they consume more CO2 than is ultimately released into the atmosphere when algae-based fuel burns. The amount of carbon removed from the environment will depend on the number of algae farms built and the efficiency with which algae can be modified to convert CO2 to fuel products. Eventually, algae farms will likely be located adjacent to CO2 producing facilities, like power plants, resulting in potentially significant CO2 sequestration benefits.


Q: Is the process capable of being replicated at the local level to increase energy efficiency and promote low-energy overhead?

    A: Absolutely. There are huge advantages to locating algae farms near urban centers. The algae consume industrial waste and contaminants, which are usually found in higher concentrations near cities. A perfect location is near a power plant, where the algae can consume flue gas and other waste, or near a wastewater treatment plant where the algae could consume significant amounts of nitrates and phosphates from the waste stream. This could result in cleaner effluent discharge, and perhaps eventually create “new” sources of non-potable water for industrial or agricultural use.


Q: Could algae-based fuels be used in developing countries to help them bypass fossil fuel dependence?

    A: Algae-based fuels (and the protein byproducts derived from their production) definitely have the potential to positively impact developing countries. The requirements for farming algae are fairly straightforward and can be done almost anywhere in the world with an adequate supply of sunshine. In Africa, for example, millions of algae acres could be farmed in its less-populated regions, resulting in a reduced dependence on foreign oil and a reliable and sustainable energy supply.

 

CCRES ALGAE PROJECT

part of 

Croatian Center of Renewable Energy Sources (CCRES)