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-?B (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-?B (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 ?–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) 

Read More..

FUCOSE

FUCOSE

#Fucose is an essential hexose deoxy sugar the human body needs to optimally communicate from cell to cell. Simply put, it plays an important role in transmitting information in the brain. Research studies show that this sugar stimulates brain development and can also influence the brain to be able to create long-term memories. This is further supported by studies in which doctors inhibited protein containing fucose; amnesia was the result.

Fucose is found in a number of places in the human body. Its location in the male testes suggests that it may play an important role during reproduction. Also found in the epidermis, it may help in maintaining skin hydration. Beyond these locations, this sugar is found at the articulation between each nerve, in the tubules of the human kidney, and in significant quantities in human breast milk.

Its important not to confuse this with the similar sounding fructose. While both are sugars that can be commonly found in the body, fructose is a simple monosaccharide sugar found in many foods. For example, you can find a high amount of fructose in baby food, salad dressing, blackberries, tree fruits, honey and even some root vegetables. On the other hand, fucose, as previously stated, can be found in the human body naturally.

Studies also show that fucose may play a role in certain diseases, such as cancer and its infection method. Though research is not yet conclusive, there is promise shown for using fucose to inhibit both breast cancer and leukemia, in addition to tumor growth, in general. Some studies have even gone as far as to conclude that this hexose deoxy sugar seems to be among the most effective sugars at attempting to prevent cancer cells from growing.

Research indicates that even taking in fucose in extremely high amounts does not seem to present any real ill side effects, though recommendations are that the average 150-pound (68.2 kg) human adult can safely handle 34 grams of this sugar on a daily basis. During urination, fucose leaves the body, so people who urinate frequently can experience a deficiency in fucose. People with rheumatoid arthritis also generally are deficient in this kind of sugar. Many people opt to take supplements to ensure they have the right amount in their body. Seaweeds such as kelp, beer yeast, and medicinal mushrooms are also a good alternative to supplements and for people who have difficulty taking pills.

#CCRES #ALGAE TEAM

Read More..

Fucus Treatments

Fucus Treatments

Fucus Treatments

Our best source of biological iodine and our best protection against thyroid disruption is to body-load with iodine contained in iodine-rich whole raw seaweeds as regular daily consumption. If our bodies have an ongoing full complement of I-127, we can better resist taking in incidental I-131. This means that eating seaweeds regularly in the diet, especially the big northern kelps, to provide both dietary iodine and protection against the ongoing I-131 hazards.
No land plants are a reliable natural source of iodine. 

Garlic grown near the sea often has relatively high amounts of biological iodine. Besides garlic, root crops, such as turnips, carrots, potatoes, parsnips, and sweet potatoes, are plant sources of iodine. However, the best natural source of biological iodine is seaweed. Any seaweed contains more available dietary iodine than any land plant. The seaweeds with the most available iodine are the giant kelps of the northern hemisphere. The highest concentrations of iodine occurs in Icelandic kelp (8000 ppm), Norwegian kelp (4000 ppm), and Maine and California kelp (1000-2000 ppm). The seaweeds with the least amounts of iodine are nori (about 15ppm) and sargassum (about 30-40 ppm). The amounts of iodine in land plants can be greatly increased by fertilizing food plants with seaweeds applied directly to the soil as topical mulch or tilled into the soil.
The complexity of many thyroid dysfunction cases precludes a simple set of all-purpose formulas. Each thyroid patient has a unique thyroid presentation. I try to compose an individualized functional treatment plan for each, using a few basic methods. Diet and behavior modification also are very important in thyroid case management. What follows are some of my treatment approaches and some general guidelines and notes:

Treatment Guideline 1: Rather uncomplicated seaweed therapy seems to help relieve many of the presenting symptoms of thyroid dysfunction. Some of the results are very likely from whole body remineralization (especially potassium, zinc, calcium, magnesium, manganese, chromium, selenium, and vanadium), in addition to thyroid gland aid from both sustained regular reliable dietary sources of biomolecular iodine and from thyroxin-like molecules present in marine algae, both the large edible seaweeds and their almost ubiquitous epiphytic micro-algae, predominantly the silica-walled diatoms. Seaweeds provide ample supplies of most of the essential trace elements required for adequate enzyme functioning throughout the body but especially in the liver and endocrine glands.

Treatment Guideline 2: Regular biomolecular seaweed iodine consumption is more than just thyroid food: it can also protect the thyroid gland from potential resident I-131-induced molecular disruption and cell death when the thyroid gland is fully iodized with I-127. The fear of eating seaweed that might be contaminated with I-131 is easily mitigated by allowing the seaweed to be stored for 50 days prior to dietary consumption; this will give enough time for most (99%) of any I-131 to decay radioactively.
A simple folk test for iodine deficiency or at least aggressive iodine uptake is to paint a 2-inch diameter round patch of USP Tincture of Iodine (strong or mild) on a soft skin area, such as the inner upper arm, the inside of the elbow, the inner thigh, or the lateral abdomen between the lowest rib and the top of the hip. If you are iodine deficient, the patch will disappear in less than 2 hours, sometimes as quickly as 20 minutes; if it fades in 2 to 4 hours, you may just be momentarily iodine needy. If it persists for more than 4 hours, you are probably iodine sufficient. Iodine deficiency seems to predispose to thyroid malignancy; this could explain the apparent thyroid cancer distribution “fans” downwind of nuclear facilities in previous ‘goiter belt’ areas. This test is of course easier to use with Caucasians and may not offer sufficient color contrast in brown-skinned people.

Treatment Guideline 3: Many patients with underactive thyroid glands complain of a sense of “coldness” or feeling cold all of the time; often they are over-dressed for warmth according to ‘thyronormal’ people’s standards. They may also present a low basal body resting temperature, as measured by taking their armpit temperature before rising in the morning. (Remember to shake down the thermometer the night before). Other symptoms may include sluggishness, gradual weight gain, and mild depression. For these patients, add 5 to 10 grams of several different whole seaweeds to the daily diet; that is, 5 to 10 grams total weight per day, not 5 to 10 grams of each seaweed. I usually suggest a mix of 2 parts brown algae (all kelps, Fucus, Sargassum, Hijiki) to one part red seaweed (Dulse, Nori, Irish moss, Gracillaria). The mixed seaweeds can be eaten in soups and salads or easily powdered and sprinkled onto or into any food. I recommend doing this for at least 60 days, about two lunar cycles or at least two menstrual cycles; watch for any changes in signs and symptoms and any change in average daily basal temperature.
Note that patients can have a normal 98.6°F temperature and still feel cold and also present many of the signs and symptoms of functional hypothyroidism. Do not insist that all hypothyroid patients must have abnormally low basal resting temperatures. If no symptoms improve or the temperature remains low (less than 98.6°F), continue seaweeds and request a TSH and T4 test. If TSH and T4 tests indicate low circulating thyroxin levels, continue seaweeds for another 2 months. It may take the thyroid that long to respond positively to continual regular presentation of adequate dietary iodine. Powdered whole seaweed may be much more effective than flakes, pieces, or granules. The powdered seaweed is best added to food immediately prior to eating; do not cook the seaweed for best results.
All corticosteroids tend to depress thyroid function. Before trying to fix the thyroid, be sure to inquire about both internal and topical steroid use, including Prednisone and topical creams. These, as well as salicylates and anticoagulants, can aggravate existing mild hypothyroidism.

Treatment Guideline 4: Partial thyroidectomy cases can be helped by regular continual dietary consumption of 3-5 grams of whole seaweeds three to four times a week. By whole seaweed I mean untreated raw dried seaweed, in pieces or powder, not reconstructed flakes or granules.

Treatment Guideline 5: Patients with thyroid glands on thyroid replacement hormone (animal or synthetic) can respond favorably to replacing part or all their entire extrinsic hormone requirement by adding dietary Fucus in 3 to 5 gram daily doses, carefully and slowly. Fucus spp. has been the thyroid folk remedy of choice for at least 5000 years. The best candidates are women who seek a less hazardous treatment than synthetic hormone (after reading variously that prolonged use of synthetic thyroid hormone increases risk for heart disease, osteoporosis, and adverse interactions with many prescribed drugs, particularly corticosteroids and antidepressants).
Fucus spp. contains di-iodotyrosine (iodogogoric acid) or DIT. Two DIT molecules are coupled in the follicular lumina of the thyroid gland by a condensing esterification reaction organized by thyroid peroxidase (TPO). This means that Fucus provides easy-to use-prefabricated thyroxine (T4) halves for a boost to weary thyroid glands, almost as good as T4. European thalassotherapists claim that hot Fucus seaweed baths in seawater provide transdermal iodine; perhaps hot Fucus baths also provide transdermal DIT.
The best results with Fucus therapy are obtained with women who were diagnosed with sluggish thyroid glands and who are or were on low or minimal maintenance replacement hormone dosages. They may remark that they miss, forget, or avoid taking their thyroid medication for several days with no obvious negative short-term sequelae; others claim to have just stopped taking their medication. I do not recommend stopping thyroid medication totally at once. Thyroxin is essential for human life and all animal life; it has a long half-life in the body of a week or more, so that a false impression of non-dependency can obtain for up to 2 months before severe or even acute hypothyroidism can manifest, potentially fatal.
Even though I personally do not recommend it, women regularly stop taking their thyroid replacement hormone, even after years of regularly and faithfully taking their medication. In many cases, their respective thyroid glands resume thyroxine production after a 2- to 3-month lag time with many of the signs and symptoms of hypothyroidism presenting while their thyroid glands move out of inactivity. This complete cessation of taking thyroid replacement can only be successful in patients who have a potentially functioning thyroid gland. Those who have had surgical or radiation removal of their thyroid glands must take thyroid hormone medication containing thyroxine to stay alive.
Fucus can be easily added to the diet as small pieces, powdered Fucus in capsules, or freeze-dried powder in capsules. Sources of Fucus in capsules are listed under Seaweed Sources at the end of this paper. The actual Fucus is much more effective than extracts. A nice note is that Fucus spp are the most abundant intertidal brown seaweeds in the northern hemisphere. This is of especial interest to those patients who might be trading one dependency for another, as seems to be the case for some. A year’s supply can be gathered in an hour or less and easily dried in a food dehydrator or in hot sun for 10 to12 hours and then in a food dehydrator until completely crunchy dry. Fucus dries down about 6 to 1 (six pounds of wet Fucus dry down to about one pound). It has a modest storage life of 8 to 12 months in completely airtight containers stored in the dark at 50° F. A year’s supply at 4 grams per day is slightly more than 3 pounds dry. Encapsulated Fucus is available from Naturespirit Herbs, Oregon’s Wild Harvest, and Eclectic Institute.

Treatment Guideline 6: Aggressive attempts to replace thyroid replacement hormone with Fucus involve halving the dose of medication each week for 4 weeks while adding 3 to 5 grams of dried Fucus to the diet daily from the beginning and continuing indefinitely. If low thyroid symptoms appear, return to lowest thyroid hormone maintenance level and try skipping medication every other day for a week, then for every other 2 days, then 3 days, etc. The intent is to establish the lowest possible maintenance dosage by patient self-evaluation and/or to determine if replacement hormones can be eliminated when the patient ingests a regular reliable supply of both biomolecular iodine and DIT. Thoughtful, careful patient self-monitoring is essential for successful treatment.

Treatment Guideline 7: A more conservative replacement schedule is similar to the aggressive approach, except that the time intervals are one month instead of one week, and the Fucus addition is in one gram increments, beginning with one gram of Fucus the first month of attempting to halve the replacement hormone dosage, and increasing the amount of Fucus by a gram each succeeding month to 5 grams per day. The conservative schedule is urged with anxious patients and primary caregivers.
There is some concern that excess (undefined) kelp (species either unknown or not mentioned) consumption may induce hypothyroidism. It seems possible. The likely explanation is an individual’s extreme sensitivity to dietary iodine: Icelandic kelp can contain up to 8000 ppm iodine; Norwegian kelp can contain up to 4000 ppm iodine. Most kelps contain 500 to 1500 ppm iodine.
The only definitive study I have seen is a report from Hokkaido, Japan, where study subjects, at a rate of 8% to 10% of total study participants, presented with iodine-induced goiter from the consumption of large amounts of one or more Laminaria species (Kombu) of large kelps, known to be rich (more than 1000 ppm) in available iodine. Reduction of both total dietary iodine and/or dietary Kombu led to complete remission of all goiters. The apparent iodine-induced goiters did not affect normal thyroid functioning in any participants. Two women in the study did not care if they had goiters and refused to reduce their Kombu intake. Note that the Japanese have the world’s highest known dietary intakes of both sea vegetables and iodine.
Reduction or elimination of seaweeds from the diet is indicated for at least a month in cases of both hyperthyroidism and hypothyroidism, to ascertain if excess dietary iodine is a contributing factor to a disease condition. Other dietary iodine sources, particularly dairy and flour products, should also be reduced and or eliminated during the same time period. Some individuals do seem to be very dietarily iodine-extraction efficient and iodine sensitive simultaneously.

Read More..

The Effects of Astaxanthin Cardiovascular Health

 

 

Atherosclerosis: 

A Silent Cardiovascular Condition that Kills 1 Person Every 3 Seconds

High blood pressure, high levels of triglycerides, oxidation of Low Density Lipoprotein (LDL) cholesterol and lowering levels of High Density Lipoprotein (HDL) cholesterol are the primary cause that leads to oxidative stress and chronic inflammation in the vessels. This condition emerges at early age and gradually compromises vascular integrity leading to atherosclerosis at a later stage of a person lifespan. Atherosclerosis is a cardiovascular condition in which fat deposits and become oxidized along the inner lining of the artery walls. This silent yet deadly build up progressively thickens, hardens and eventually blocks the arteries leading to sudden and severe circulatory complications including vascular ischemia, stroke or heart attack. Cardiovascular and circulatory deaths related to atherosclerosis accounts for 29% of all deaths globally; the primary cause of death in EU (42%), Eastern Europe (48%), UK (39%), North America (49%), China (34%), South America (31%); Middle East (31%) and India (29%) – World Health Report, 2010.

Salmon Consumption and Lower Incidence of Cardiovascular Diseases Among Japanese. Just a Coincidence?

The cardiovascular and circulatory benefits of natural astaxanthin are evident among Japanese who are the uppermost consumers of food containing astaxanthin (AX) in the world and have the lowest incidences of heart diseases amongst developed countries. As the French paradox of cardiovascular health is connected to “sipping red-wine” and Italians longevity to “olive oil dressed” salads, Japanese cardiovascular resilience can be associated with consumption of “astaxanthin-soaked” salmon. In fact, a growing number of scientific evidence points to a robust link between natural astaxanthin and cardiovascular health – 30 cardiovascular specific research publications including 10 clinical studies. Research suggests that oral supplementation of astaxanthin may reduce the risks of cardiovascular diseases by reducing hypertension while enhancing blood rheology, capillary circulation and vascular resilience.

The Effects of Astaxanthin on Atherosclerosis Prevention and Development

Astaxanthin Increase HDL Cholesterol and Decrease Serum Triglycerides

For every 1 mg/dl increase in good cholesterol HDL, the risk of cardiovascular diseases drops by 3%. In fact, baby boomers with low-HDL (> 40mg/dL) increase their chances of experiencing coronary events by 50%. Recent studies suggest that individuals with low HDL cholesterol who also have high triglycerides levels are 11 times more likely to develop cardiovascular diseases. Achieving a significant increase of HDL is notoriously hard because it requires drastic lifestyle changes, so often ending with modest results or sudden relapses.
Recent research suggests that astaxanthin supplementation can support lifestyle changers by synergizing HDL increasing effect with decreased level of serum triglycerides. Two recent studies demonstrated that astaxanthin consumption can steadily increase HDL cholesterol in both healthy and less healthy individuals -both as preventive and therapeutic use. Yoshida et al., (2009) conducted the first ever randomized, placebo-controlled human study to evaluate astaxanthin effect on dyslipidemia and metabolic syndrome. Sixty-one hyper-triglyceride subjects between 42-47 years old (BMI 24 mg/kg), received 0 (placebo), 6 mg, 12mg, 18mg of astaxanthin daily for 12 weeks. While the placebo group did not change their existing condition, the astaxanthin groups increased their HDL cholesterol by 11%, 15% and 7% respectively and decreased their serum triglycerides level by 17%, 25% and 24% respectively (figure 1).

Figure 1. Astaxanthin increase HDL cholesterol and decrease Serum Triglycerides (STR). Subjects with lower levels of HDL and higher levels of STR are 11 times more likely to develop cardiovascular diseases (Yoshida et al., 2009) 61 hyper- triglyceride subjects between 42-47 yo; (BMI 24 mg/kg), received 0 (placebo), 6 mg, 12mg, 18mg of astaxanthin per day for 12 weeks

In a recent clinical study, 73 subjects between 20-60 years of age who received 4mg of natural astaxanthin per day for 4 weeks had their serum triglycerides level decreased by 25 %(Satoh et al., 2009). In another study conducted in Japan, 15 healthy adults increased their HDL by 6% after ingesting 9mg/daily of astaxanthin for 8 weeks (Matsumaya et al., 2010). In 2007, Hussein et al., has shown that astaxanthin reduced the size of fat cells in rats, which lead to a lower risk of cardiovascular complications and chronic inflammation (figure 2).

Figure 2. Astaxanthin reduced the size of fat cells. Large cells usually indicate higher risk of fat-oxidation chronic inflammation and oxidative stress, which are the leading causes of cardiovascular diseases (x10) (Hussein et al., 2006)

Astaxanthin Decrease Red Blood Cells Oxidation and Lipid-Peroxidation

High levels of triglycerides and low levels of HDL also increase the likelihood of fat-oxidation in vessels and formation of "wounds" in the inner lining of artery walls (endothelium) leading to chronic inflammation and oxidative stress; this situation causes degradation, narrowing and thickening of arteries. Three recent clinical studies have robustly pointed to astaxanthin ability to reduce fat peroxidation in blood plasma. In a randomized-double-blind placebo study, 33 overweight subjects received 5mg or 20mg astaxanthin daily for 3 weeks. Their lipid peroxidation markers plasma MDA Level (mmol) and plasma ISP (ng/mL) decreased by 30% and 60% in average (Choi et al., 2011).
In another randomized double blind placebo controlled study, 30 subjects between 50 and 69 years of age received 0 (placebo), 6 or 12mg astaxanthin daily for 12 weeks (Nakagawa et al., 2011). The amount of oxidized red blood cells (PLOOH um0l/ml) decreased by 17% and 24% respectively(figure 3).

Figure 3. Astaxanthin reduces red blood cells oxidation (RBCO) in senior subjects. RBCO cells has high correlation with neuro-degenerative (eg. dementia) and cardiovascular diseases (eg. heart attack) (Nakagawa et al., 2011) 30 subjects (15 F and 15 M) between 50 and 69 years of age , BMI 27·5 kg/m² received 0 (placebo), 6 or 12mg astaxanthin per day for 12 weeks

In 2007, Karppi et al., conducted a randomized double blind conducted placebo controlled study with 40 non-smoking subjects between 19-33 years of age who received 0 (placebo) or 8mg of astaxanthin daily for 12 weeks. Their lipid peroxidation markers -plasma-15-hydroxy fatty acidsdecreased by 60% and plasma-12-hydroxy fatty acids by 36%. In 2000, Iwamoto et al., has also shown that astaxanthin inhibited LDL oxidation in human subjects. Professor Aoi from Kyoto Prefectural University, has shown that astaxanthin limits exercise-induced cardiac oxidation damage in mice.

Astaxanthin Enhance Biomarkers of Anti-oxidant Healthiness in the Blood Plasma

Low antioxidant activity in the blood correlates with high incidences of stroke, neurological impairment in stroke patients and cardiovascular diseases. Therefore, it is crucial to monitor the biomarkers of antioxidant capacity in the blood when assessing the efficacy of an active ingredient. In a randomized double blind study, 33 overweight subjects received 5mg or 20mg astaxanthin daily for 3 weeks. Their plasma Superoxide Dismutase Level (SOD) (U/mL) and Plasma Total Antioxidant Capacity (TAC) Level (mmol) increased 45% and 19% respectively. (Choi et al., 2011) (figure 4).
Other studies have produced similar results using different assessment methods. In an open label clinical study, 35 postmenopausal women were treated with astaxanthin daily dose of 12 mg for 8 weeks (Yonei et al., 2009). Astaxanthin supplementation increased biological antioxidant potential in the blood plasma by 5% in 8 weeks. In addition, Camera et al., suggested that astaxanthin protects and synergize with our endogenous antioxidant systems (superoxide dismutase, catalase and glutathione) from early degradation when subjected to oxidative stress (Camera et al., 2008).

Figure 4. Astaxanthin increases Plasma SOD Level and Plasma TAC level. Low levels of SOD and TAC correlates with higher incidences of stroke, neurological impairment and cardiovascular diseases (Choi et al., 2011) 33 subjects received 5mg or 20mg astaxanthin x day for 3 weeks; BMI (25.0 -30.0 kg/m²) - aged 25.Normal Body Subjects – 10 non-intervention subjects (20.0 < BMI?24.9 kg/m²) age 26

Astaxanthin Decrease Chronic Inflammation that comprise Blood Vessels Integrity

In the presence of oxidized cells in the endothelial lesions, macrophages white blood cells infiltrate in affected areas to clear away pathogens and dead cells. Yet, in the attempt to clean up the oxidized areas, macrophages may get overweighed with excessive lipoproteins and unable to leave the artery walls. This peculiar but common situation triggers a cascade of chronic inflammatory responses and pro-oxidant activities that degraded the structural integrity of the vessels. Therefore, up-regulated activity of oxidized LDL via macrophage induced inflammation is central to the initiation and progression of atherosclerosis. They are closely associated with plaque development, aggravation and ruptures.
A recent study shows that astaxanthin decreased macrophage occupied lesion areas and therefore inflammation in the vessels of rabbits by 40% compared to control group (figure 5). Furthermore, rabbits that ingested 4mg astaxanthin everyday for 24 weeks decreased programmed cell death (apoptosis) by 42% and cell death (necrosis) by 17% in the aorta (Li et al., 2004).

Figure 5. Astaxanthin decrease chronic inflammation and cell death in the inner lining of the vessels. Chronic inflammation and apoptosis in the endothelium dramatically accelerates vascular degradation and atherosclerotic plaque formation. (Li et al., 2004) Rabbits ingested 4mg of placebo, Vitamin E or astaxanthin everyday for 24 weeks.

In-vitro study provides further evidences that astaxanthin (5-10uM) decreases macrophages related activation (SR-A and CD36) by 48% and 58% respectively (Kishimoto et al., 2009). A recent animal studies show that astaxanthin could ameliorate endothelial dysfunction by significantly improving the level of substances important for the regulation of vascular integrity. In more details, treatment with astaxanthin for 42 days decreased serum oxidized LDL cholesterol, aortic MDA levels, attenuated endothelium-dependent vasodilatory to acetylcholine, up-regulate eNOS expression and decreased LDL cholesterol receptor expression (figure 6).

Figure 6. Astaxanthin treatment improved markers of endothelial dysfunction by reducing oxidation of LDL cholesterol and MDA. Higher levels of LDL oxidation and MDA expression highly correlates with structural damages in blood vessels and impairment of blood flow. (Zhao et al., 2011) Diabetic rats were treated with 10 mg/kg of astaxanthin or olive oil for 42 days.

Animal studies have also shown that astaxanthin ameliorated structural changes in the blood vessels - reduction in wall thickness by 47% and improved vascular tone by 36% in spontaneously hypertensive rats (Hussein et al., 2006). Such structural changes was observed in the reduction of the number of branched elastin bands and improved vessel wall to lumen thickness ratio.
In another study, 24 weeks supplementation of natural astaxanthin reduced levels of MMP3 expression in the aorta of rabbits - a crucial factor that lead to a degradation of elastin and collagen structures which determines the mechanical properties of connective tissues in the vessels (figure 7). In the experiment, astaxanthin enhanced plaque stability leading to a significant reduction of plaque ruptures (Li et al., 2004).

Figure 7. Astaxanthin inhibit MMP over-expression in the thoracic aorta. Over-expression of MMP is a crucial factor that leads to the degradation of vascular integrity and escalation of atherosclerotic plaque ruptures (Li et al., 2004) Animal Study – Rabbits ingested AX 4mg/ Kg of body weight daily x 24weeks

Astaxanthin Improving Vascular Resilience and Capillary Blood Flow

Good circulation, quality of blood and resilient vessels are the key features required to fight development and progression of atherosclerosis. Blood rich in antioxidants bring nutrients and oxygen to organs while removing waste through a smooth vascular resilience and capillary flow.
Recent human studies suggest that 6mg daily of astaxanthin can enhance blood flow by 10% in terms of capillary transit time -how fast the blood runs through the vessels (Miyawaki et al., 2008). Another complementary study showed that astaxanthin decreased lower limb vascular resistance by 17% - the degree to which the blood vessels impede the flow of blood (Iwabayashi et al., 2009).(figure 8) High resistance causes an increase in blood pressure, which increases the workload of the heart. In 2005, Nagaki et al., conducted another randomized double-blind study in which 36 subjects who received oral astaxanthin, 6mg/day for 4 weeks experienced a 4% improvement in capillary blood flow (Nagaki et al., 2005).

Figure 8. astaxanthin decreased lower limb vascular resistance (LLVR) – the degree to which the vessels impede the flow of blood. LLVR increase blood pressure and circulatory complications that lead to peripheral vascular diseases, venous thrombosis and painful claudication (Yonei et al., 2009) 35 healthy postmenopausal women (BMI 22.1) were included in the study, treated with astaxanthin daily dose of 12 mg for 8 weeks.

Astaxanthin Reduces Hypertension

A series of human studies suggest that astaxanthin decreases blood pressure by improving blood flow and vascular tone. In a recent clinical study, 73 subjects, between 20-60 years of age, who received 4mg of astaxanthin for day for 4 weeks showed a significant decrease in systolic blood pressure (Satoh et al., 2009). In another study, 15 healthy subjects, between 27-50 of age, who received 9mg/day of astaxanthin for 12 weeks had their diastolic blood pressure decreased significantly (Matsuyama et al., 2010).
A series of animal studies have largely replicated the effects of astaxanthin found in human studies (e.g. Ruiz et al., 2010; Preuss, 2011).

Outlook

Clinical studies suggests that oral supplementation of natural astaxanthin (4mg-12mg) may reduce the risk cardiovascular complications by enhancing blood rheology, lipid-metabolism, capillary circulation, vascular resilience and the endogenous antioxidant defense. Other clinical studies have also shown that astaxanthin reduce lipid-peroxidation, LDL cholesterol, blood pressure and DNA damage. Mechanism of action includes inhibition of macrophage-induced inflammation in the endothelium, oxidative stress-induced apoptosis and MPP-induced-structural degradation of the vessels. Furthermore, recent studies have also outlined that astaxanthin ameliorates nitric oxide dependent vessels dilation and reduce sensitivity to the angiotensin.

References

1. Aoi et al., (2003). Astaxanthin limits exercise-induced skeletal and cardiac muscle damage in mice. Antioxidants & Redox Signaling. 5(1):139-44.
2. Hussein et al., (2005b). Antihypertensive potential and mechanism of action of astaxanthin II. Vascular reactivity and hemorheology in spontaneously hypertensive rats. Biol. Pharm. Bull., 28(6):967-971.
3. Hussein et al., (2006b). Antihypertensive potential and mechanism of action of astaxanthin: III. Antioxidant and histopathological effects in spontaneously hypertensive rats. Biol. Pharm. Bull., 29(4):684-688.
4. Hussein et al., (2005a). Antihypertensive and Neuroprotective Effects of Astaxanthin in Experimental Animals. Biol. Pharm. Bull., 28(1): 47-52.
5. Iwabayashi et al., (2009). Efficacy and safety of eight-week treatment with astaxanthin in individuals screened for increased oxidative stress burden. Journal of Anti-Aging Medicine., 6(4):15-21
6. Iwamoto et al., (2000). Inhibition of low-density lipoprotein oxidation by astaxanthin. Journal of Atherosclerosis Thrombosis. 7(4):216-22.
7. Karppi et al., (2007). Effects of astaxanthin supplementation on lipid eroxidation. Int J Vitam Nutr Jan; 77 (1): 3-11.
8. Kishimoto et al., (2009). Astaxanthin suppresses scavenger receptor expression and matrix metalloproteinase activity in macrophages. European Journal of Nutrition., 49(2):17-26
9. Li et al., (2004). Alpha-tocopherol and astaxanthin decrease macrophage infiltration, apoptosis and vulnerability in atheroma of hyperlipidaemic rabbits. Journal of Molecular and Cellular Cardiology., 37:969-978.
10. Matsuyama et al., (2010) A Safety Study on the Long-Term Consumption of Astaxanthin in Healthy Human Volunteer. Japanese Journal of Complementary and Alternative Medicine., (7):43-50. (Translated from Japanese)
11. Miyawaki et al., (2005). Effects of Astaxanthin on Human Blood Rheology. Journal of Clinical Therapeutics and Medicines., 21(4):421-429.7.
12. Murillo (1992). Hypercholesterolemic effect of canthaxanthin and astaxanthin in rats. Arch. Latinoam Nutr., 42(4):409-413.
13. Preuss et al., (2009). Astaxanthin lowers blood pressure and lessens the activity of the eroxi-angiotensin system in Zucker Fatty Rats., Journal of Functional Foods., I:13-22
14. Yoshida et al., (2010). Administration of natural astaxanthin increases serum HDL-cholesterol and adiponectin in subjects with mild hyperlipidemia., 209 (2): 520-3.
15. Nakagawa et al., (2011). Antioxidant effect of astaxanthin on phospholipid peroxidation in human erythrocytes British Journal of Nutrition., (31):1-9
16. Choi et al., (2011). Effects of Astaxanthin on Oxidative Stress in Overweight and Obese Adults Phytother. Research (in-press).
17. Satoh et al., (2009).Preliminary Clinical Evaluation of Toxicity and Efficacy of a New Astaxanthin-rich Hameotoccus Pluvialis. J. Clin. Biochem. Nutr., 44: 280–284.
18. Hussein et al., (2007). Astaxanthin ameliorates features of metabolic syndrome in SHR/NDmcr-cp. Life Sci., 16;80(6):522-9.
19. Preuss, et al., (2011). High Dose Astaxanthin Lowers Blood Pressure and Increases Insulin Sensi-tivity in Rats: Are These Effects Interdependent?., 8(2):126-138.
20. Ruiz et al., (2010). Astaxanthin-enriched-diet reduces blood pressure and improves cardiovascular parameters in spontaneously hypertensive rats. Pharmacological Research., 63(1):44-50
21. Zhao et al., (2011). Ameliorative effect of astaxanthin on endothelial dysfunction in streptozotocin-induced diabetes in male rats. Arzneimittelforschung., 61(4): 239-246.

 CCRES special thanks to 
Mr. Mitsunori Nishida, 
President of Corporate Fuji Chemical Industry Co., Ltd.

Croatian Center of Renewable Energy Sources (CCRES) 

Read More..

The Effects of Astaxanthin Weight Control

 

 

Physical Endurance and Muscle Recovery

 

Work, Sport, Leisure – in fact all physical activity will generate reactive oxygen species (ROS); the more intense the activity the greater number of free radicals. ROS are shown to have damaging effects on muscle performance and recovery. Published and on-going research, focused on improving endurance and reducing recovery time, are showing dramatic benefits linked to the potent carotenoid - astaxanthin. These findings are bringing astaxanthin to the forefront as a dietary supplement for professional athletes and physically active people.

Important to physical activity are our mitochondrial cells, often referred to as the “power stations of the cell” , which provide as much as 95% of our body’s pure energy (primarily by the burning of muscle glycogen and fatty acids). Unfortunately, a portion of this energy produces highly reactive and damaging ROS. ROS damage cells by triggering peroxidation of the cell membrane components, and oxidation of DNA and proteins. Furthermore, ROS continue to affect muscles even after the strenuous exercise has ceased. ROS activate the inflammation response whereby monocytes migrate into the muscle tissue causing additional cell damage. Often we will notice the onset of muscle damage during recovery in the form of tiredness and soreness. In addition to improving muscle performance through devised exercise regime, the sports research community is looking at other methods, such as nutrition to fuel and protect the body under extreme physical conditions. In the past, Vitamins E and C helped make the use of antioxidants a popular tool against oxidative damage during intense physical activity. Today, informed by current research we can point to astaxanthin as the antioxidant of choice for sports performance. Astaxanthin demonstrated 3 important physical benefits in clinical trials and supporting studies. Astaxanthin increased endurance, reduced muscle damage and improved lipid metabolism.

Astaxanthin Boosts Endurance

In a randomized, double-blind, placebo controlled study on healthy men supplemented with 4 mg astaxanthin per day for up to 6 months at Karolinska Institute, Sweden, standardized exercise tests demonstrated that the average number of knee bends performed increased only in the astaxanthin treated group at 3 months, and by the 6 month significant improvements were observed (Figure 1) (Malmsten & Lignell, 2008).

Figure 1. Increase in strength/endurance (Malmsten & Lignell, 2008)

   

Astaxanthin improved strength/endurance at 3 and 6 months determined by the average number of knee bends per person.

Figure 2. Effect of astaxanthin on swimming time (Ikeuchi et al., 2006)  

Astaxanthin improves endurance in a dose-dependant manner.

In another study, Aoi et al., (2008) demonstrated that astaxanthin may modify muscle metabolism by its antioxidant property and result in improved muscle performance and weight loss benefits. After 4 weeks the mice running time to exhaustion had significantly improved by up to 20 % , (2002) of Juntendo University, Japan, demonstrated by using 1200 meter track athletes, that a daily dose of 6 mg per day for 4 weeks resulted in their bodies accumulating lower levels of lactic acid (Figure 3). Ikeuchi et al., (2006) also reported the same findings and furthermore, astaxanthin efficacy had a dose-dependent response (Figure 4).

Figure 3. Reduction of lactic acid build-up after astaxanthin supplementation in track subjects (Sawaki et al., 2002) 

Figure 4. Effect of astaxanthin on blood lactate during swimming for 15 minutes (Ikeuchi et al., 2006)  

Astaxanthin reduced build-up of lactic acid in a dose-dependant manner.

In a double blind controlled placebo study, healthy women (n= 32; age-23-60) who ingested 12 mg of astaxanthin for 6 weeks significantly reduced their body fat (4%) when conducting routine walking exercise, compared to a placebo group. In addition, while control group increased their lactic acid by 31% compared to the astaxanthin group - only 13%

The Mechanism

The mechanism behind muscle endurance is based on several findings. Generally, astaxanthin protected the skeletal muscle from the increased damage of oxidative stress generated by physical activity. Furthermore, astaxanthin increased the metabolism of lipids as the main source of energy production by protecting the carnitine palmitoyltransferase I (CPT I) involved in fatty acid transport into mitochondria. Aoi et al., (2003) of Kyoto Prefecture University used mice models that may partially explain the efficacy of astaxanthin; they compared control, exercise placebo, and astaxanthin treated exercise groups after intense physical activity. 4-hydroxy-2-nonenal-modified-protein (4-HNE) stain analyses of the calf (gastrocnemius) muscles revealed significantly lower peroxidation damage (Figure 5).

Figure 5. Effect of astaxanthin on 4-HNE-modifed proteins in leg muscle before and after exercise (Aoi et al., 2003)

Other biochemical markers for oxidative damage and inflammation such as DNA, (2003) also explained that astaxanthin directly modulates inflammation caused by the release of the pro-inflammatory cytokines and mediators. In vivo and in vitro tests demonstrate that astaxanthin inhibits the I?B Kinase (IKK) dependant activation of the Nuclear Factor-kB (NF-?B) pathway, a key step in the production of pro-inflammatory cytokines and mediators. Aoi et al., 2008 also demonstrated increased lipid metabolism compared to carbohydrate as the main source of energy during strenuous activity (Figure 6). Furthermore, analysis of the mitochondrial lipid transport enzyme known as carnitine palmitoyltransferase I (CPT I) revealed increased fat localization (Figure 7) and reduction of oxidative damage in the presence of astaxanthin (Figure 8). CPT I is important because it regulates fatty acyl-CoA entry into the mitochondria in the oxidation of fatty acids in muscle. Exercise-induced ROS may partly limit utilization of fatty acid via diminishing CPT I activity.

Figure 6. Fat substrate utilization increased with astaxanthin (Aoi et al., 2008)

   

 Calculated from the respiratory exchange ratio (RER) and oxygen consumption. Values are means ± SE obtained from 8 mice.

Figure 7. Increased amount of FAT/CD36 that coimmunoprecipitated with CPT I skeletal muscle after a single session of exercise at 30 m/min for 30 min (Aoi et al., 2008)  

Values are means ± SE obtained from 6 mice.

Figure 8. Astaxanthin reduced the amount of HEL-modified CPT1 in skeletal muscle after a single session of exercise at 30m/min for 30min (Aoi et al., 2008)  

Values are means ± SE obtained from 6 mice.

Outlook

 

Strenuous physical activity generates high levels of ROS which affect muscle performance and metabolism of lipids. New research shows that astaxanthin can modify muscle metabolism via its antioxidant effect, resulting in the improvement of muscle function during exercise. Therefore, astaxanthin is expected to be useful for physically active people as well as athletes.

References

1. Aoi W, Naito Y, Sakuma K, Kuchide M, Tokuda H, Maoka T, Toyokuni S, Oka S, Yasuhara M, Yoshikawa T. (2003). Astaxanthin limits exercise-induced skeletal and cardiac muscle damage in mice. Antioxid Redox Signal, 5(1):139-144.
2. Aoi W, Naito Y, Takanami Y, Ishii T, Kawai Y, Akagiri S, Kato Y, Osawa T, Yoshikawa T. (2008). Astaxanthin improves muscle lipid metabolism in exercise via inhibitory effect of oxidative CPT I modification. Biochem. Biophys. Res. Com., 366:892–897.
3. Fukamauchi, M. (2007). Food Functionality of astaxanthin-10: Synergistic effects of astaxanthin-10 intake and aerobic exercise. Food Style 21, 11(10). [In Japanese]
4. Ikeuchi M, Koyama T, Takahashi J, Yazawa K. (2006). Effects of astaxanthin supplementation on exercise-induced fatigue in mice. Bio. Pharm. Bull., 29(10):2106-2110.
5. Lee SJ, Bai SK, Lee KS, Namkoong S, Na HJ, Ha KS, Han JA, Yim SV, Chang K, Kwon YG, Lee SK, Kim YM. (2003). Astaxanthin Inhibits Nitric Oxide Production and Inflammatory Gene Expression by Suppressing I?B Kinase-dependent NF-?B Activation. Mol. Cells, 16(1):97-105.
6. Malmsten C, Lignell A. (2008). Dietary supplementation with astaxanthin rich algal meal improves muscle endurance – a double blind study on male students. Carotenoid Science 13:20-22.
7. Sawaki K, Yoshigi H, Aoki K, Koikawa N, Azumane A, Kaneko K, Yamaguchi M. (2002). Sports performance benefits from taking natural astaxanthin characterized by visual activity and muscle fatigue improvements in humans. J Clin.Therap. Med., 18(9):73- 88.

CCRES special thanks to 

 Mr. Mitsunori Nishida, 

 
President of Corporate Fuji Chemical Industry Co., Ltd.

Croatian Center of Renewable Energy Sources (CCRES) 

Read More..

The Effects of Astaxanthin Gastric Health

 

 

Astaxanthin for Dyspepsia and Helicobacter pylori

 

Dyspepsia is the general term given to a variety of digestive problems localized in the upper abdominal region. Typical symptoms for example include stomach pain, gas, acid-reflux or bloating. Dyspepsia is like the stomach version of the irritable bowel syndrome and its symptoms may appear at any age or to any gender. The medical approach to dyspepsia involves looking for treatable causes and addressing them if identified. Failing that, doctors suggest treatments by trial-and-error. The problem associated with this non-standardized approach involves drugs that may not work, may cause side effects and exacerbate the patient’s condition brought on by stressful attempts to cure symptoms.
To understand the benefits of astaxanthin in dyspepsia, it is necessary to categorize specific types; most common forms are either non-ulcer dyspepsia or gastric dyspepsia. Non-ulcer dyspepsia problems usually do not have an identifiable cause, but fortunately, for most cases it is non-disease related and therefore temporary. On the other hand, gastric type dyspepsia is more severe and linked to identifiable causes. For example, the bacterial infection of Helicobacter pylori is a commonly known cause. Pathological symptoms of H. pylori infection include high levels of oxidative stress and inflammation in the stomach lining and symptoms like gastric pain and acid reflux., H. pylori can contribute to mild and severe kinds of symptoms, but on the other hand, people who are H. pylori positive can remain asymptomatic whereas others may develop into clinical problems. It is still unclear what triggers the severe form of infection and how the bacteria is passed on, but scientists suggested using strong antioxidants like astaxanthin for therapy and better long term protection.

Helicobacter pylori in Gastric Dyspepsia

This Gram-negative bacterium is present in approximately half of the world population, and typically resides in the human gastric epithelium (stomach lining). H. pylori infection is generally acknowledged as the main cause for type B gastritis, peptic ulcer disease and gastric cancer. The pathogenesis of this infection is partly due to the immunological response as shown by Bennedsen et al., (1999). Astaxanthin (200 mg/kg body weight) fed to H. pylori infected mice for 10 days exhibited signs of improved immune system. Normally, the T-helper1 (Th1) response exacerbates inflammation and epithelial cell damage due to infection, but the astaxanthin treated mice responded with a mixed Th1/Th2-response (Figure 1), which lowered gastric inflammation (Figure 2) and bacterial loads (Figure 3). Furthermore, the findings by Wang et al., (2000) also supported the idea that a diet supplemented with astaxanthin or vitamin C in mice lowered inflammation after 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 infected control mice; which continued to develop severe gastritis.

Figure 1. IL-4 release of splenocytes after restimulation with H. pylori sonicate (Bennedsen et al., 1999)  

Astaxanthin improved the cytokine IL-4 response (Th2 T-cell) to the presence of H. pylori (in vitro).

Figure 2. Gastric inflammation (antrum + corpus) (Bennedsen et al., 1999)

   

Astaxanthin reduced gastric inflammation in Helicobacter pylori infected mice.

Figure 3. Bacterial load (antrum + corpus) (Bennedsen et al., 1999)  

Astaxanthin reduced Helicobacter pylori colonization of the stomach of infected mice.

Figure 4. Amount of lipid peroxidation products (MDA and 4-hydroxyalkenals) during H. pylori infection (Wang et al., 2000) 

 

Lipid peroxidation levels lowered in H. pylori infected mice after treatment with astaxanthin or Vitamin C.

The success of astaxanthin in dyspepsia animal models prompted further prospective human studies. In 1999, the first clinical study performed in collaboration with the Centre for Digestive Diseases, Australia, involved 10 H. pylori positive subjects (non-ulcer) with typical dyspeptic symptoms such as heartburn and gastric pain, were each treated with 40 mg daily dose of astaxanthin for 21 days. 10 clinical parameters assessed the efficacy before and after the treatment period. The gastric pain, heartburn and total clinical symptoms results showed a significant drop of 66%, 78% and 52% drop respectively (Figure 5). Furthermore, follow-up checks 27 days after the cessation of astaxanthin intake (a total of 49 days from day 0), showed that the dyspeptic symptoms remained low (Lignell et al., 1999). In summary, astaxanthin effectively controlled the dyspepsia symptoms, and H. pylori eradication trend was observed, but not significant.

Figure 5. Total Clinical Symptoms (Lignell et al., 1999)  

Astaxanthin reduced total grade of clinical symptoms in H. pylori positive non-ulcer dyspeptic subjects after 21 days. Low symptom score continued even up to 28 days after treatment ceased.

Reflux in Non-Ulcer Dyspepsia

 

Approximately one in four people experience dyspepsia at some time that are linked to common causes such as food types, stress, stomach ulcers, or acid reflux (stomach acid backs-up into the esophagus). If the exact causes of non-ulcer dyspepsia are unknown, there are no standardized treatments that exist to effectively treat the patient. The usual procedure involves the problematic remedies of acid blocking medicines, painkillers or antibiotics. However, drug treatment faces problems with 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.
Astaxanthin efficacy in non-ulcer dyspepsia was demonstrated in a 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.

Figure 6. Reflux-syndrome 

   

Reduced reflux-syndrome score of non-ulcer dyspepsia patients treated with 16 mg and 40 mg astaxanthin.

Outlook

There are considerable overlaps in a number of gastrointestinal disorders that may be treatable with conventional medicine, but what if it does not work? In that case, astaxanthin may be useful, particularly against H. pylori positive gastritis and non-ulcer dyspepsia acid reflux. The mechanisms of action include the following: decreasing oxidative stress by astaxanthin’s potent antioxidant property; controlling bacterial infection by shifting the immune response; and alleviating dyspeptic symptoms by retarding inflammation. Furthermore, these results infer that acid reflux in connection with either H. pylori positive or negative conditions can still expect improvements with astaxanthin.

References

1. Bennedsen M, Wang X, Willen R. Treatment of H. pylori infected mice with antioxidant astaxanthin reduces gastric inflammation, bacterial load and modulates cytokine release by splenocytes. Immunol Lett. 1999. 70: 185-189.
2. Kupcinskas L, Lafolie P, Lignell A, Kiudelis G, Jonaitis L, Adamonis K, Andersen LP, Wadstrom T. Efficacy of the natural antioxidant astaxanthin in the treatment of functional dyspepsia in patients with or without Helicobacter pylori infection: A prospective, randomized, double blind, and placebo-controlled study. Phytomedicine 2008. 15: 391–399.
3. Lignell A, Surace R, Bottiger P, Borody TJ. Symptom improvement in Helicobacter pylori positive non-ulcer dyspeptic patient after treatment with the carotenoid astaxanthin. In: 12th International Carotenoid Symposium, Cairns, Australia, 18-23 July 1999.
4. Wang X, Willen R, Wadstrom T. Astaxanthin rich algal meal and vitamin C inhibit Helicobacter pylori infection in BALB/cA mice. Antimicrob Agents Chemother. 2000. 44: 2452-2457.

CCRES special thanks to 

 Mr. Mitsunori Nishida, 

 
President of Corporate Fuji Chemical Industry Co., Ltd.

Croatian Center of Renewable Energy Sources (CCRES) 

Read More..

The Effects of Astaxanthin Hypertension

 

 

Astaxanthin Reduces Hypertension

 

Epidemiological and clinical data suggest that dietary carotenoids such as astaxanthin may protect against cardiovascular disease (CVD) which includes hypertension. This condition is associated with blood vessel dysfunction, altered contractility and tone; mediated by relaxant (nitric oxide NO; prostacyclin) and constrictor factors (thromboxane; endothelin) in the blood. Furthermore, blood flow properties serve an important role in the pathological complications seen in atherosclerosis and coronary heart disease. Research presented here suggests that astaxanthin may be useful as part of an antioxidant therapy to alleviate hypertension (Figure 1).

Figure 1. Mechanisms by which Astaxanthin reduces hypertension

Reduction of Arterial Blood Pressure

An early study involving a composition of carotenoids have been used against hypertension or high blood pressure (BP), but Hussein et al., (2005a) published the first study involving astaxanthin with spontaneously hypertensive rats (SHR) and stroke prone (SHR-SP). This study investigated the effects of astaxanthin on the aortic vessel blood pressure (BP) in relation to endothelium and nitric oxide (NO) to elucidate mechanism and response.

Figure 2. Astaxanthin (5mg/kg/day) treated SHR reduced mean blood pressure. Hussein et al., 2005b.

In a double blind controlled placebo study conducted in Japan, 20 healthy postmenopausal women, who ingested 12 mg everyday for 4 weeks, reduced their systolic and diastolic blood pressure by 7% and 4%
In another study, 15 healthy subjects, between 27-50 of age, who received 9mg/day of astaxanthin for 12 weeks had their diastolic blood pressure decreased by 6% (Matsuyama et al., 2010).
A series of animal studies have largely replicated the effects of astaxanthin found in human studies (Ruiz et al., 2010; Preuss, 2009; Preuss, 2011).

Figure 3. Open Label Clinical Study. 73 subjects between 20-60 years of age received 4mg of astaxanthin x day for 4 weeks (Sato et al 2009)

Mechanism of Anti-hypertension

The antihypertensive mechanism may be in part explained by the changes of vascular reactivity and hemorheology.
Microchannel Array Flow Analysis (MC-FAN) measured a significant increase of blood flow of 11% (Figure 3) in the astaxanthin treated group.

Figure 4. Open Label Clinical Study 35 healthy postmenopausal women (BMI 22.1) were included in the study, treated with astaxanthin daily dose of 12 mg for 8 weeks

In a human study conducted by Iwabayashi et.al., (2009) , 20 healthy women who ingested 6mg / day for 8 weeks increased ABI (ankle brachial pressure index) by 4% suggesting a reduction of lower limb vascular resistance. Another human study also prove that oral administration of 6 mg/day of astaxanthin for 10 days enhanced capillary blood flow by 10%.

Figure 5. Astaxanthin (6 mg/day) supplementation for 10 days improves blood flow in humans as tested by MC-FAN. Miyawaki et al., 2005.

Figure 6. Astaxanthin increases relaxant and reduces constrictor mechanisms to help reduce blood pressure in SHR.

 

Indeed, Hussein et al., (2006b) demonstrated that 5 mg/day of astaxanthin for 7 weeks decreased vascular wall thickness by 47%.

Figure 7. A) Coronary artery wall is thinner and lumen is wider in astaxanthin treated rats. B) Elastin bands are also fewer in number and less elastic compared to the control groups which also show intense and branched elastine feature (C). Hussein et al., (2006a).

Outlook

The oxidative status and physiological condition during hypertension are successfully mediated by astaxanthin. The mechanisms of action include improved blood rheology, modulation of constrictor and dilator factors and blood vessel remodelling. Although, these findings are based on spontaneous hypertensive rat models, these serve as a solid basis for extending the hypothesis to human clinical trials.

References

1. Hussein G, Nakamura M, Zhao Q, Iguchi T, Goto H, Sankawa U, Watanabe H. (2005)a. Antihypertensive and neuroprotective effects of astaxanthin in experimental animals. Biol. Pharm. Bull., 28(1):47-52.
2. Hussein G, Goto H, Oda S, Iguchi T, Sankawa U, Matsumoto K, Watanabe H. (2005)b. Antihypertensive potential and mechanism of action of astaxanthin II. Vascular reactivity and hemorheology in spontaneously hypertensive rats. Biol. Pharm. Bull., 28(6):967-971.
3. Hussein G, Goto H, Oda S, Sankawa U, Matsumoto K, Watanabe H. (2006)a. Antihypertensive potential and mechanism of action of astaxanthin: III. Antioxidant and histopathological effects in spontaneously hypertensive rats. Biol. Pharm. Bull. 29(4):684-688.
4. Hussein G, Sankawa U, Goto H, Matsumoto K, Watanabe H. (2006)b. Astaxanthin, a Carotenoid with Potential in Human Health and Nutrition. J. Nat. Prod., 69(3):443 – 449.
5. 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.
6. Kudo Y, Nakajima R, Matsumoto N. (2002). Effects of astaxanthin on brain damages due to ischemia. Carotenoid Science (5):25.
7. Li W, Hellsten A, Jacobsson LS, Blomqvist HM, Olsson AG, Yuan XM. (2004). Alpha-tocopherol and astaxanthin decrease macrophage infiltration, apoptosis and vulnerability in atheroma of hyperlipidaemic rabbits. J. Mol. Cell. Cardio., 37(5):969-978.
8. Miyawaki H, Takahashi J, Tsukahara H, Takehara I. (2005). Effects of astaxanthin on human blood rheology. J. Clin. Thera. Med., 21(4):421-429.
9. 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.

CCRES special thanks to 

 Mr. Mitsunori Nishida, 

 
President of Corporate Fuji Chemical Industry Co., Ltd.

Croatian Center of Renewable Energy Sources (CCRES) 

Read More..