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Exotic Destinations

One of the islands in the middle is Sulawesi, an island of rocks thrust up from tetonic plate collisions millions of years ago.  Indonesia is famous for many things. The copy lovers may be familiar with three of them, Sumatra Coffee, New Guinea Highlands coffee and Sulawesi – Kalosi coffee.  The southern part of the mountainous island is home of  Torajaland, a land of an ancient culture, an unspoilt paradise, a land of heavenly kings. It seems like a long lost valley obscured by clouds.  Toraja land in Sulawesi, is indeed one of the most exotic and beautiful places I have ever had coffee beans from.

Sulawesi – Kalosi Coffee

In South Sulawesi, in an area known as Torajaland, the natives brew a rare and delicious coffee. The culture, thousands of years old, has small coffee trees surrounding many natives huts. Each family will grow and harvest their own small collection of coffee trees.  A few companies, including Peets purchases these coffee beans for the rest of the world, few of which know where these rare beans come from.

Price / Value

The coffee beans make the journey from this exotic island paradise for a lot cheaper than you can. Peets sells Sulawesi – Kalosi Coffee for only 14.95 per pound. You can purchase it in one of four grinds, or whole beans. I purchase whole bean coffee from my closest Peets coffee shop (some 25 miles away) on Thursdays because Peets roasts their beans on Wednesdays and ships them to all their shops overnight.  The more popular and widely available Sumatra coffee (the island to the West of Sulawesi) by comparison is $12.95 a pound. (This Indonesian coffee is even widely available in supermarkets that carry Peets Coffee) Coffee from New Guinea is 13.95 per pound. Although the Sulawesi coffee is the most expensive of the region, it still remains very reasonable, and when you try a cup, you won’t mind that it is a bit more expensive than all those brands sitting on your supermarket shelf.

Preparation

You may order this ground, or purchase whole beans as I did. I ground 6 tablespoons of beans in a Breville Burr Grinder and added 36 ounces of water, 6 oz to a table spoon. (I filled my Bunn coffee pot up to the 6 cup mark, and poured the water into the top). If you like a big cup or mug of coffee, 6 cups is actually equal to 3 cups of coffee. I use a medium fine grind designed for coffee makers, and a Bunn GRX coffee maker. Sometimes I use a French press, but not this morning.

A bit of exotic paradise arrives in my morning cup

The first thing I noticed about the Sulawesi beans is that they don’t smell quite the same as many coffee beans, it isn’t quite a coffee smell. Sulawesi has the same earthy body as Sumatra does, but it is a bit more lively and there is a slightly nutty taste to it. If you like Sumatra for example, but find it to be a bit too smooth for you, you may enjoy this more complex cup from Sumatra. There are definitely more flavors going on in this cup than the average cup of coffee, not as much as say, Kenyan coffee, but still pretty interesting. Those who like a smooth sweeter coffee may not like this one, I wouldn’t describe it as smooth or sweet. It isn’t bitter, it just doesn’t have a sweet aftertaste.

Most coffee lovers describe this coffee as multidimensional aromatic character with prominent herbal, nutty, and pleasantly sweet woody notes.

I mostly agree, but found the slightly woody taste interesting, but not particularly sweet. Perhaps its just because I enjoyed a cup of Guatemala coffee yesterday that did have a midly sweet chocolate taste.

Comparing this coffee to the other coffees of Indonesia, I found that I enjoyed the smoother Sumatra more. My favorite Indonesian coffee is still a blend of beans from Java and Arabia, Peets Arabian Mocha-Java.

Summary

All in all, I enjoyed my cup of Sulawesi – Kalosi coffee, but I am not sure I would rush out to order it again. For complex coffee, I prefer the more exotic Kenyan beans, and for a nearly identical but smoother taste, I prefer the Sumatra from the neighboring island. I have not yet tried the New Guinea highlands coffee, but when I do, I will review it.

Overall this is a a very good coffee, and it is a nice compromise between the complex coffees of Kenya and the smooth coffee of Sumatra. For those who prefer sweeter coffees, this may not be the bean of choice.

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Everyone in today’s competitive environment is looking for an edge, and caffeine can provide the little boost that gives you the advantage you need to succeed. The key is knowing what caffeine can do for you and how to use it effectively.

The Advantages of Caffeine

Here are just some of caffeine’s amazing advantages:

• Improves your ability to think clearly and solve problems, and can actually raise your IQ
• Increases your short-term memory, helps you concentrate, and relieves boredom
• Is a powerful antioxidant, combating muscle damage and helping you to stay younger
• Improves your mood and overcomes depression, creating an “attitude of success”
• Helps you run, swim, and cycle longer and faster
• Increases the painkilling power of common analgesics and is itself a strong pain reliever
• Grows brain cells in the areas of the brain responsible for long-term memory

Already widely acclaimed by many of the foremost academic researchers in the world, including Dr. Paul Kulkosky, whose foreword introduces the book, The Caffeine Advantage delivers a comprehensive program for working smarter, not harder, and for improving mood, athletic fitness, and mental performance.

If you want more useful source regarding the health benefits of caffeine and coffee, please read my other great post :

No Link Between Heart Failure and Coffee Intake

A civet eats the berries for their fleshy pulp. In its stomach, proteolytic enzymes seep into the beans, making shorter peptides and more free amino acids. Passing through a civet’s intestines the beans are then defecated, having kept their shape. After gathering, thorough washing, sun drying, light roasting and brewing, these beans yield an aromatic coffee with much less bitterness, widely noted as the most expensive coffee in the world.

Kopi luwak is produced mainly on the islands of Sumatra, Java, Bali and Sulawesi in the Indonesian Archipelago, and also in the Philippines (where the product is called motit coffee in the Cordillera and kape alamid in Tagalog areas) and also in East Timor (where it is called kafé-laku). Weasel coffee is a loose English translation of its name cà phê Chồn in Vietnam, where popular, chemically simulated versions are also produced.

Kopi is the Indonesian word for coffee. Luwak is a local name of the Asian palm civet in Sumatra. Palm civets are primarily frugivorous (fuit eating), feeding on berries and pulpy fruits such as from ficus trees and palms. Civets also eat small vertebrates, insects, ripe fruits and seeds.

When coffee plants are put into civet habitats, the civets forage on only the ripest and sweetest berries. Hence, farmers would often find their best coffee berries missing in the morning after civets had been feeding and they were seen as pests. Meanwhile farmers hoping to save their crop gathered the civet droppings and found these beans, which were darkened and more brittle, yielded a coffee with unusual taste and lack of bitterness.

Production

Early production began when beans were gathered in the wild from where a civet would defecate as a means to mark its territory. On farms, civets are either caged or allowed to roam within defined boundaries.

Coffee berries are eaten by a civet for their fruit pulp. After spending about a day and a half in the civet’s digestive tract the beans are then defecated in clumps, having kept their shape and still covered with some of the fleshy berry’s inner layers. They are gathered, thoroughly washed, sun dried and given only a light roast so as to keep the many intertwined flavors and lack of bitterness yielded inside the civet.

Cultivars, blends and tastes

Kopi luwak is a name for many specific cultivars and blends of arabica, robusta, liberica, excelsa or other beans eaten by civets, hence the taste can vary greatly. Nonetheless, kopi luwak coffees have a shared aroma profile and flavor characteristics, along with their lack of bitterness. Coffee critic Chris Rubin has said, “The aroma is rich and strong, and the coffee is incredibly full bodied, almost syrupy. It’s thick with a hint of chocolate, and lingers on the tongue with a long, clean aftertaste.”^[3]

Kopi luwak tastes unlike heavy roasted coffees, since roasting levels range only from cinnamon color to medium, with little or no caramelization of sugars within the beans as happens with heavy roasting. Moreover, kopi luwaks which have very smooth profiles are most often given a lighter roast. Iced kopi luwak brews may bring out some flavors not found in other coffees.

Sumatra is the world’s largest regional producer of kopi lowak. Sumatran civet coffee beans are mostly an early arabica variety cultivated in the Indonesian archipelago since the seventeenth century. Tagalog cafe alamid (or alamid cafe) comes from civets fed on a mixture of coffee beans and is sold in the Batangas region along with gift shops near airports in the Philippines.

Research

Research by food scientist Massimo Marcone at the University of Guelph in Ontario, Canada showed that the civet’s endogenous digestive secretions seep into the beans. These secretions carry proteolytic enzymes which break down the beans’ proteins, yielding shorter peptides and more free amino acids. Since the flavor of coffee owes much to its proteins, there is a hypothesis that this shift in the numbers and kinds of proteins in beans after being swallowed by civets brings forth their unique flavor. The proteins are also involved in non-enzymatic Maillard browning reactions brought about later by roasting. Moreover, whilst inside a civet the beans begin to germinate by malting which also lowers their bitterness.^[4][5][3]

Safety of Kopi Luwak

At the outset of his research Marcone doubted the safety of kopi luwak. However, he found that after the thorough washing, levels of harmful organisms were insignificant. Roasting at high temperature has been cited as making the beans further safe after washing.^[3]

Economics

Kopi luwak is the most expensive coffee in the world, selling for between US $100 and $600 per pound.^[1] It is sold by weight mainly in Japan and the United States and served in Southeast Asian coffeehouses by the cup. Sources vary widely as to annual worldwide production.^[6]

Sales by the cup

In November 2006 Herveys Range Heritage Tea Rooms, a small cafe in the hills outside Townsville in Queensland, Australia, put kopi luwak coffee on its menu at AUD50.00 (US $33.00) a cup, selling about seven cups a week, which gained nationwide Australian and international press.^[7] In April 2008 the brasserie at Peter Jones department store in London’s Sloane Square began selling a blend of kopi luwak and Blue Mountain called Caffe Raro for £50 (US $99.00) a cup.^[8]

Simulated civet coffee

Civet coffee is a popular coffeehouse drink in Vietnam, where producers make simulated civet coffee.

In 1996 German scientists hired by Trung Nguyen Coffee Company in Viet Nam isolated six digestive enzymes in the civet’s digestive tract and a patented synthetic soak with these enzymes was developed to simulate the natural effect. Trung Nguyen’s simulated product is called Legendee and is often the first kopi luwak-like coffee tasted by tourists in Southeast Asia.

Some kopi luwak simulations are not enzyme soaks but rather, roasts of high quality beans with added flavorings.

Kopi muncak

Kopi muncak (or kopi muntjak) is made from the dung of barking deer (muntjac) found throughout Southeast Asia. Unlike civet coffee, Kopi muncak is mostly gathered in the wild, chiefly in Malaysia and the Indonesian Archipelago.

References



Cocoa Content is the Key

Lead author Dr. Brian Buijsse (German Institute of Human Nutrition, Nuthetal, Germany) told heartwire: “This shows that habitual consumption of chocolate is related to a lower risk of heart disease and stroke that is partly explained by blood-pressure reduction. The risk reduction is stronger for stroke than for MI, which is logical because it appears that chocolate and cocoa have a pronounced effect on BP [blood pressure], and BP is a higher risk factor for stroke than for MI.” Buijsse and colleagues report their findings online March 31, 2010 in the European Heart Journal.

However, Buijsse cautions that only small amounts of chocolate were associated with the benefits and it is too early to give recommendations on chocolate consumption: “Maybe it’s a boring message, but it’s a little too early to come up with recommendations, because chocolate contains so many calories and sugar, and obesity is already an epidemic. We have to be careful.

“However, he added, that if people did want to treat themselves, they would be better off choosing small amounts of chocolate, preferably dark chocolate, over other sweet snacks. “We know it is the cocoa content in chocolate that is important, so the higher the cocoa content, the better.”

Dr. Steffen Desch (University of Leipzig, Heart Center, Germany), who was not involved with this study but who has performed research on the effects of chocolate on blood pressure, told heartwire: “This is an interesting study that adds to the growing body of evidence that flavanol-rich chocolate might be associated with health benefits. Several epidemiological studies (including the Zuphten Elderly Study, by the same first author) and even more physiological trials have been published before.”

“What is missing now is a large-scale randomized trial of flavanol-rich chocolate versus control. The most reasonable end point would probably be the change in blood pressure between groups.” However, Desch added, “the major problems in designing such a study are the lack of funding and finding an appropriate control substance. To the best of my knowledge, there is no commercially available flavanol-free chocolate that offers the distinct bitter taste and dark color inherent to cocoa-rich chocolate.”

Biggest Chocolate Consumers Had Lowest Blood Pressure

Buijsse and colleagues followed 19 357 people, aged between 35 and 65, who were participants in the Potsdam arm of the European Prospective Investigation into Cancer (EPIC). They received medical checks, including blood pressure and height and weight measurements at the start of the study (1994–1998), and they also answered questions about their diet, lifestyle, and health, including how frequently they ate 50-g bars of chocolate.

The research was conducted before the health benefits of chocolate and cocoa were recognized, so no differentiation was made between milk, dark, and white chocolate in the study. But in a subset analysis of 1568 participants later asked to recall their chocolate intake over a 24-hour period, 57% ate milk chocolate, 24% dark chocolate, and 2% white chocolate.

Participants were divided into quartiles according to their level of chocolate consumption. Those in the top quartile, eating around 7.5 g of chocolate a day, had blood pressure that was about 1 mm Hg (systolic) and 0.9 mm Hg (diastolic) lower than those in the bottom quartile.

In follow-up questionnaires, sent out every two or three years until December 2006, the participants were asked whether they had had a heart attack or stroke, information that was subsequently verified by medical records from general physicians or hospitals. Death certificates from those who had died were also used to identify MIs and strokes.

“Our hypothesis was that because chocolate appears to have a pronounced effect on blood pressure, chocolate consumption would lower the risk of strokes and heart attacks, with a stronger effect being seen for stroke,” explained Buijsse.

Those Eating Most Chocolate Had Half the Risk of Stroke

During the eight years, there were 166 MIs (24 fatal) and 136 strokes (12 fatal); people in the top quartile had a 27% reduced risk of MI and nearly half the risk (48%) of stroke, compared with those in the lowest quartile. The relative risk of the combined outcome of MI and stroke for top vs bottom quartile was 0.61 (p=0.014).

The researchers found that lower baseline blood pressure explained 12% of the reduced risk of the combined outcome, but even after taking this into account, those in the top quartile still had their risk reduced by a third (32%) compared with those in the bottom quartile over the duration of the study.

To put this in terms of absolute risk, Buijsse said if people in the group eating the least amount of chocolate increased their chocolate intake by 6 g a day, 85 fewer heart attacks and strokes per 10 000 people could be expected to occur over a period of about 10 years.

He says it appears that flavanols in chocolate are responsible for the beneficial effects, causing the release of nitric oxide, which contributes to lower BP and improves platelet function.

Dr Frank Ruschitzka (University Hospital, Zurich, Switzerland) agrees. He said in a European Society of Cardiology statement [2]: “Basic science has demonstrated quite convincingly that dark chocolate particularly, with a cocoa content of at least 70%, reduces oxidative stress and improves vascular and platelet function.”

Only Small Amounts of Chocolate Beneficial; Don’t Eat Too Much

Buissje said this work builds on his earlier small trial–the Zuphten Elderly Study–performed in 500 men in Holland, which showed that chocolate consumption lowered overall cardiovascular mortality. “Due to the small size of this study, we were not able to differentiate between stroke and MI in this, but now we are able to look at stroke and MI separately, so it’s a nice addition,” he notes.

And the findings are in line with an intervention study that showed that eating around 6 g of chocolate a day–one small square of a 100-g bar–might lower cardiovascular disease risk, he says. “So the effects are achieved with very small amounts.”

British Heart Foundation dietician Victoria Taylor made the same point: “It’s important to read the small print with this study. The amount consumed on average by even the highest consumers was about one square of chocolate a day or half a small chocolate Easter egg in a week, so the benefits were associated with a fairly small amount of chocolate.

“Some people will be tempted to eat more than one square; however, chocolate has high amounts of calories and saturated fat . . . two of the key risk factors for heart disease,” she noted in a statement [3].

Ruschitzka similarly urged caution: “Before you rush to add dark chocolate to your diet, be aware that 100 g of dark chocolate contains roughly 500 calories. As such, you may want to subtract an equivalent amount of calories, by cutting back on other foods, to avoid weight gain.”

The researchers report no conflicts of interest.

References

1. Buijsse, B, Weikert C, Drogan D et al. Chocolate consumption in relation to blood pressure and risk of CV disease in German adults. Eur Heart J 2010: DOI:10.1093/eurheartj/ehq068. Available at: http://eurheartj.oxfordjournals.org.
2. European Society of Cardiology. Study shows chocolate reduces blood pressure and risk of heart disease [press release]. Available here.
3. British Heart Foundation. Eggcellent news in time for Easter! [press release]. March 30, 2010. Available here.
4. www.medscape.com

I got explanation from his family that during his teenage up to his death he had unhealthy lifestyle. As a student, he accustomed to drink instant energy drink and to consume instant noodle almost everyday. As we know that both kind of modern-processed food are rich of artificial food additives, such as MSG and artificial colorings and sweeteners. I hope you could learn from this tragic case: never consume too much food containing artificial food additives.

Many people who have chronic kidney disease don’t know it, because the early signs can be very subtle. It can take many years to go from chronic kidney disease (CKD) to kidney failure. Some people with CKD live out their lives without ever reaching kidney failure.

However, for people at any stage of kidney disease, knowledge is power. Knowing the symptoms of kidney disease can help you get the treatment you need to feel your best. If you or someone you know has one or more of the following symptoms of kidney disease, or you are worried about kidney problems, see a doctor for blood and urine tests. Remember, many of the symptoms can be due to reasons other than kidney disease. The only way to know the cause of your symptoms is to see your doctor.

Symptom 1:

Changes in Urination

Kidneys make urine, so when the kidneys are failing, the urine may change. How?

• You may have to get up at night to urinate.
• Your urine may be foamy or bubbly.
• You may urinate more often, or in greater amounts than usual, with pale urine.
• You may urinate less often, or in smaller amounts than usual with dark colored urine.
• Your urine may contain blood.
• You may feel pressure or have difficulty urinating.

What patients said:

“When you go to use the restroom, you couldn’t get it all out. And it would still feel just like tightness down there, there was so much pressure.”

“My urine is what I had started noticing. Then I was frequently going to the bathroom, and when I got there, nothing’s happening.”

“I was passing blood in my urine. It was so dark. And when I went to the hospital they thought I was lying about what color it was.”

Symptom 2:

Swelling

Failing kidneys don’t remove extra fluid, which builds up in your body causing swelling in the legs, ankles, feet, face, and/or hands.

What patients said:

“I remember a lot of swelling in my ankles. My ankles were so big I couldn’t get my shoes on.”

“My sister, her hair started to fall out, she was losing weight, but her face was really puffy, you know, and everything like that, before she found out what was going on with her.”

“Going to work one morning, my left ankle was swollen, real swollen, and I was very exhausted just walking to the bus stop. And I knew then that I had to see a doctor.”

Symptom 3:

Fatigue

Healthy kidneys make a hormone called erythropoietin (a-rith’-ro-po’-uh-tin) that tells your body to make oxygen-carrying red blood cells. As the kidneys fail, they make less erythropoietin. With fewer red blood cells to carry oxygen, your muscles and brain become tired very quickly. This condition is called anemia, and it can be treated.

What patients said:

“I was constantly exhausted and didn’t have any pep or anything.”

“I would sleep a lot. I’d come home from work and get right in that bed.”

“It’s just like when you’re extremely tired all the time. Fatigued, and you’re just drained, even if you didn’t do anything, just totally drained.”

Symptom 4:

Skin Rash/Itching

Kidneys remove wastes from the bloodstream. When the kidneys fail, the buildup of wastes in your blood can cause severe itching.

What patients said:

“It’s not really a skin itch or anything, it’s just right down to the bone. I had to get a brush and dig. My back was just bloody from scratching it so much.”

“My skin had broke out, I was itching and scratching a lot.”

Symptom 5:

Metallic Taste in Mouth/Ammonia Breath

A buildup of wastes in the blood (called uremia) can make food taste different and cause bad breath. You may also notice that you stop liking to eat meat, or that you are losing weight because you just don’t feel like eating.

What patients said:

“Foul taste in your mouth. Almost like you’re drinking iron.”

“You don’t have the appetite you used to have.”

“Before I started dialysis, I must have lost around about 10 pounds.”

Symptom 6:

Nausea and Vomiting

A severe buildup of wastes in the blood (uremia) can also cause nausea and vomiting. Loss of appetite can lead to weight loss.

What patients said:

“I had a lot of itching, and I was nauseated, throwing up all the time. I couldn’t keep anything down in my stomach.”

“When I got the nausea, I couldn’t eat and I had a hard time taking my blood pressure pills.”

Symptom 7:

Shortness of Breath

Trouble catching your breath can be related to the kidneys in two ways. First, extra fluid in the body can build up in the lungs. And second, anemia (a shortage of oxygen-carrying red blood cells) can leave your body oxygen-starved and short of breath.

What patients said:

“At the times when I get the shortness of breath, it’s alarming to me. It just fears me. I think maybe I might fall or something so I usually go sit down for awhile.”

“I couldn’t sleep at night. I couldn’t catch my breath, like I was drowning or something. And, the bloating, can’t breathe, can’t walk anywhere. It was bad.”

“You go up a set of stairs and you’re out of breath, or you do work and you get tired and you have to stop.”

Symptom 8:

Feeling Cold

Anemia can make you feel cold all the time, even in a warm room.

What patients said:

“I notice sometimes I get really cold, I get chills.”

“Sometimes I get really, really cold. It could be hot, and I’d be cold.”

Symptom 9:

Dizziness and Trouble Concentrating

Anemia related to kidney failure means that your brain is not getting enough oxygen. This can lead to memory problems, trouble with concentration, and dizziness.

What patients said:

“I know I mentioned to my wife that my memory—I couldn’t remember what I did last week, or maybe what I had 2 days ago. I couldn’t really concentrate, because I like to work crossword puzzles and read a lot.”

“I was always tired and dizzy.”

“It got to the point, like, I used to be at work, and all of the sudden I’d start getting dizzy. So I was thinking maybe it was my blood pressure or else diabetes was going bad. That’s what was on my mind.”

Symptom 10:

Leg/Flank Pain

Some people with kidney problems may have pain in the back or side related to the affected kidney. Polycystic kidney disease, which causes large, fluid-filled cysts on the kidneys and sometimes the liver, can cause pain.

What patients said:

“About 2 years ago, I was constantly going to the bathroom all the time, the lower part of my back was always hurting and I was wondering why…and they diagnosed that kidney problem.”

“And then you’re having to get up all time through the night, and then you have the side ache, a backache, and you can’t move.”

“At night, I would get a pain in my side. It was worse than labor pain. And I’d be crying and my husband would get up, everybody, rubbing my legs.”

The 19 months old baby died due to failure of breathing organ , around 15.00 local time, 10 April 10th, 2010. “Because of breathing failure and delayed operation,” said Bilqis’ mother, Dewi Farida to the press.

Bilqis was treated at RSUP Dr.Kariadi to wait for her fulfillment of medical requirements before operation. When Minister of Health Endang Rahayu Sedyaningsih visited her at March 13th, Bilqis’ weight was less 0,2 kilogram from the required weight. The doctor required that her weight at least 9 kilogram before the operation can be done.

Meanwhhile, a team of 50 specialist doctors had been prepared to execute Bilqis’ opertaion. The team led by Dr. Yulianto.

The budget needed for her operation was Rp 800 million up to Rp 1 billion. Bilqis was prepared to receive liver donor from her own mother. The operation was estimated would be undertaken within 12-15 hours.

What is Biliary Atresia?

Biliary atresia is a serious but rare disease of the liver that affects newborn infants. It occurs in about one in 10,000 children and is more common in girls than in boys and in Asian and African-American newborns than in Caucasian newborns. The cause of biliary atresia is not known, and treatments are only partially successful. Biliary atresia is the most common reason for liver transplantation in children in the United States and most of the Western world.

The liver damage incurred from biliary atresia is caused by injury and loss (atresia) of the bile ducts that are responsible for draining bile from the liver. Bile is made by the liver and passes through the bile ducts and into the intestines where it helps digest food, fats, and cholesterol. The loss of bile ducts causes bile to remain in the liver. When bile builds up it can damage the liver, causing scarring and loss of liver tissue. Eventually the liver will not be able to work properly and cirrhosis will occur. Once the liver fails, a liver transplant becomes necessary. Biliary atresia can lead to liver failure and the need for liver transplant within the first 1 to 2 years of life.

Symptoms of Biliary Atresia

The first sign of biliary atresia is jaundice, which causes a yellow color to the skin and to the whites of the eyes. Jaundice is caused by the liver not removing bilirubin, a yellow pigment from the blood. Ordinarily, bilirubin is taken up by the liver and released into the bile. However, blockage of the bile ducts causes bilirubin and other elements of bile to build up in the blood.

Jaundice may be difficult for parents and even doctors to detect. Many healthy newborns have mild jaundice during the first 1 to 2 weeks of life due to immaturity of the liver. This normal type of jaundice disappears by the second or third week of life, whereas the jaundice of biliary atresia deepens. Newborns with jaundice after 2 weeks of life should be taken to the doctor to check for a possible liver problem.

Other signs of jaundice are a darkening of the urine and a lightening in the color of bowel movements. The urine darkens from the high levels of bilirubin in the blood spilling over into the urine, while stool lightens from a lack of bilirubin reaching the intestines. Pale, grey, or white bowel movements after 2 weeks of age are probably the most reliable sign of a liver problem and should prompt a visit to the doctor.

What Causes Biliary Atresia?

The cause of biliary atresia is not known. The two types of biliary atresia appear to be a “fetal” form, which arises during fetal life and is present at the time of birth, and a “perinatal” form, which is more typical and does not become evident until the second to fourth week of life. Some children, particularly those with the fetal form of biliary atresia, often have other birth defects in the heart, spleen, or intestines.

An important fact is that biliary atresia is not an inherited disease. Cases of biliary atresia do not run in families; identical twins have been born with only one child having the disease. Biliary atresia is most likely caused by an event occurring during fetal life or around the time of birth. Possibilities for the “triggering” event may include one or a combination of the following factors:

• infection with a virus or bacterium
• a problem with the immune system
• an abnormal bile component
• an error in development of the liver and bile ducts

Research on the cause of biliary atresia is of great importance. Progress in the management and prevention of biliary atresia can only come from a better understanding of its cause or causes.

How to Treat Biliary Atresia?

Surgery. If biliary atresia appears to be the cause of the jaundice in the newborn, the next step is surgery. At the time of surgery the bile ducts can be examined and the diagnosis confirmed. For this procedure, the infant is sedated. While the infant is asleep, the surgeon makes an incision in the abdomen to directly examine the liver and bile ducts. If the surgeon confirms that biliary atresia is the problem, a Kasai procedure will usually be performed on the spot.

Kasai procedure (hepato-portoenterostomy). If biliary atresia is the diagnosis, the surgeon generally goes ahead and performs an operation called the “Kasai procedure,” named after the Japanese surgeon who developed this operation. In the Kasai procedure, the bile ducts are removed and a loop of intestine is brought up to replace the bile ducts and drain the liver. As a result, bile flows from the small bile ducts straight into the intestine, bypassing the need for the larger bile ducts completely. (More about the Kasai procedure follows.)

Liver transplant. If the Kasai procedure is not successful, the infant usually will need a liver transplant within the first 1 to 2 years of life. Children with the fetal form of biliary atresia are more likely to need liver transplants—and usually sooner—than infants with the typical perinatal form. The pattern of the bile ducts affected and the extent of damage can also influence how soon a child will need a liver transplant. (More about liver transplantation follows.)

The Kasai Procedure

The Kasai procedure can restore bile flow and correct many of the problems of biliary atresia. This operation is usually not a cure for the condition, although it can have an excellent outcome. Without this surgery, a child with biliary atresia is unlikely to live beyond the age of 2. The operation works best if done before the infant is 90 days old and results are usually better in younger children.

The improved results of the surgery make the early diagnosis of biliary atresia very important, preferably before the infant is several months old and has suffered permanent liver damage. Some infants with biliary atresia who undergo a successful Kasai operation are restored to good health and can lead a normal life without jaundice or major liver problems.

The Kasai Procedure

Unfortunately, the Kasai procedure is not always successful. If bile flow is not restored, the child will likely develop worsening liver disease and cirrhosis and require liver transplantation within the first 1 to 2 years of life. In addition, the Kasai operation, even when initially successful, may not totally restore normal liver development and function. A child with biliary atresia may slowly develop cirrhosis and related complications and require a liver transplant later in childhood.

While the Kasai procedure has been a great advance in the management of biliary atresia, improvements in the operation and clinical management of children who undergo it are needed to improve the outcomes of children with this disease.

Hope Through Research

Researchers are studying the possible causes of biliary atresia and new ways to diagnose and treat it. One of the largest research initiatives is the Biliary Atresia Research Consortium (BARC), a network of centers funded by the National Institute of Diabetes and Digestive and Kidney Diseases.

The network comprises 10 liver disease and transplant centers and one data-coordinating center. The centers work together to coordinate research and share ideas and resources. The network will enroll infants with biliary atresia in a large study to evaluate the best ways of managing the disease and to carry out clinical trials of new and promising treatments or approaches for diagnosis and monitoring the disease. Because biliary atresia is a rare disease, only a network of centers can identify enough infants with this disease to carry out studies of new therapies.

Centers will collect blood, tissue, and other samples from infants with biliary atresia so researchers can learn more about biliary atresia and find better treatments. An important goal of BARC is to help find the causes of biliary atresia and recommend ways for its early detection and proper management.

For More Information

The American Liver Foundation

75 Maiden Lane, Suite 603

New York, NY 10038

Phone: 1–800–GO–LIVER (465–4837)

Fax: 212–483–8179

Email: info@liverfoundation.org

Internet: www.liverfoundation.org

Canadian Liver Foundation

2235 Sheppard Avenue East, Suite 1500

Toronto, Ontario M2J 5B5

Canada

Phone: 1–800–563–5483

Fax: 416–491–4952

Email: clf@liver.ca

Internet: www.liver.ca

Children’s Liver Association for Support Services

25379 Wayne Mills Place, Suite 143

Valencia CA 91355

Phone: 1–877–679–8256

Fax: 661–263–9099

Email: info@classkids.org

Internet: www.classkids.org

The Children’s Organ Transplant Association

2501 West COTA Drive

Bloomington, IN 47403

Phone: 1–800–366–2682

Fax: 812–336–8885

Internet: www.cota.org

Although oxidation reactions are crucial for life, they can also be damaging; hence, plants and animals maintain complex systems of multiple types of antioxidants, such as glutathione, vitamin C, and vitamin E as well as enzymes such as catalase, superoxide dismutase and various peroxidases. Low levels of antioxidants, or inhibition of the antioxidant enzymes, causes oxidative stress and may damage or kill cells.

As oxidative stress might be an important part of many human diseases, the use of antioxidants in pharmacology is intensively studied, particularly as treatments for stroke and neurodegenerative diseases. However, it is unknown whether oxidative stress is the cause or the consequence of disease. Antioxidants are also widely used as ingredients in dietary supplements in the hope of maintaining health and preventing diseases such as cancer and coronary heart disease. Although initial studies suggested that antioxidant supplements might promote health, later large clinical trials did not detect any benefit and suggested instead that excess supplementation may be harmful.^[2] In addition to these uses of natural antioxidants in medicine, these compounds have many industrial uses, such as preservatives in food and cosmetics and preventing the degradation of rubber and gasoline.

History

The term antioxidant originally was used to refer specifically to a chemical that prevented the consumption of oxygen. In the late 19th and early 20th century, extensive study was devoted to the uses of antioxidants in important industrial processes, such as the prevention of metal corrosion, the vulcanization of rubber, and the polymerization of fuels in the fouling of internal combustion engines.^[3]

Early research on the role of antioxidants in biology focused on their use in preventing the oxidation of unsaturated fats, which is the cause of rancidity.^[4] Antioxidant activity could be measured simply by placing the fat in a closed container with oxygen and measuring the rate of oxygen consumption. However, it was the identification of vitamins A, C, and E as antioxidants that revolutionized the field and led to the realization of the importance of antioxidants in the biochemistry of living organisms.^[5][6]

The possible mechanisms of action of antioxidants were first explored when it was recognized that a substance with anti-oxidative activity is likely to be one that is itself readily oxidized.^[7] Research into how vitamin E prevents the process of lipid peroxidation led to the identification of antioxidants as reducing agents that prevent oxidative reactions, often by scavenging reactive oxygen species before they can damage cells.^[8]

The oxidative challenge in biology

The structure of the antioxidant vitamin ascorbic acid (vitamin C).

A paradox in metabolism is that while the vast majority of complex life on Earth requires oxygen for its existence, oxygen is a highly reactive molecule that damages living organisms by producing reactive oxygen species.^[9] Consequently, organisms contain a complex network of antioxidant metabolites and enzymes that work together to prevent oxidative damage to cellular components such as DNA, proteins and lipids.^[1][10] In general, antioxidant systems either prevent these reactive species from being formed, or remove them before they can damage vital components of the cell.^[1][9] However, since reactive oxygen species do have useful functions in cells, such as redox signaling, the function of antioxidant systems is not to remove oxidants entirely, but instead to keep them at an optimum level.^[11]

The reactive oxygen species produced in cells include hydrogen peroxide (H₂O₂), hypochlorous acid (HOCl), and free radicals such as the hydroxyl radical (·OH) and the superoxide anion (O₂⁻).^[12] The hydroxyl radical is particularly unstable and will react rapidly and non-specifically with most biological molecules. This species is produced from hydrogen peroxide in metal-catalyzed redox reactions such as the Fenton reaction.^[13] These oxidants can damage cells by starting chemical chain reactions such as lipid peroxidation, or by oxidizing DNA or proteins.^[1] Damage to DNA can cause mutations and possibly cancer, if not reversed by DNA repair mechanisms,^[14][15] while damage to proteins causes enzyme inhibition, denaturation and protein degradation.^[16]

The use of oxygen as part of the process for generating metabolic energy produces reactive oxygen species.^[17] In this process, the superoxide anion is produced as a by-product of several steps in the electron transport chain.^[18] Particularly important is the reduction of coenzyme Q in complex III, since a highly reactive free radical is formed as an intermediate (Q·⁻). This unstable intermediate can lead to electron “leakage”, when electrons jump directly to oxygen and form the superoxide anion, instead of moving through the normal series of well-controlled reactions of the electron transport chain.^[19] Peroxide is also produced from the oxidation of reduced flavoproteins, such as complex I.^[20] However, although these enzymes can produce oxidants, the relative importance of the electron transfer chain to other processes that generate peroxide is unclear.^[21][22] In plants, algae, and cyanobacteria, reactive oxygen species are also produced during photosynthesis,^[23] particularly under conditions of high light intensity.^[24] This effect is partly offset by the involvement of carotenoids in photoinhibition, which involves these antioxidants reacting with over-reduced forms of the photosynthetic reaction centres to prevent the production of reactive oxygen species.^[25][26]

Metabolites

Overview

Antioxidants are classified into two broad divisions, depending on whether they are soluble in water (hydrophilic) or in lipids (hydrophobic). In general, water-soluble antioxidants react with oxidants in the cell cytosol and the blood plasma, while lipid-soluble antioxidants protect cell membranes from lipid peroxidation.^[1] These compounds may be synthesized in the body or obtained from the diet.^[10] The different antioxidants are present at a wide range of concentrations in body fluids and tissues, with some such as glutathione or ubiquinone mostly present within cells, while others such as uric acid are more evenly distributed (see table below). Some antioxidants are only found in a few organisms and these compounds can be important in pathogens and can be virulence factors.^[27]

The relative importance and interactions between these different antioxidants is a very complex question, with the various metabolites and enzyme systems having synergistic and interdependent effects on one another.^[28][29] The action of one antioxidant may therefore depend on the proper function of other members of the antioxidant system.^[10] The amount of protection provided by any one antioxidant will also depend on its concentration, its reactivity towards the particular reactive oxygen species being considered, and the status of the antioxidants with which it interacts.^[10]

Some compounds contribute to antioxidant defense by chelating transition metals and preventing them from catalyzing the production of free radicals in the cell. Particularly important is the ability to sequester iron, which is the function of iron-binding proteins such as transferrin and ferritin.^[30] Selenium and zinc are commonly referred to as antioxidant nutrients, but these chemical elements have no antioxidant action themselves and are instead required for the activity of some antioxidant enzymes, as is discussed below.

Ascorbic acid

Ascorbic acid or “vitamin C” is a monosaccharide antioxidant found in both animals and plants. As one of the enzymes needed to make ascorbic acid has been lost by mutation during human evolution, it must be obtained from the diet and is a vitamin.^[43] Most other animals are able to produce this compound in their bodies and do not require it in their diets.^[44] In cells, it is maintained in its reduced form by reaction with glutathione, which can be catalysed by protein disulfide isomerase and glutaredoxins.^[45][46] Ascorbic acid is a reducing agent and can reduce, and thereby neutralize, reactive oxygen species such as hydrogen peroxide.^[47] In addition to its direct antioxidant effects, ascorbic acid is also a substrate for the antioxidant enzyme ascorbate peroxidase, a function that is particularly important in stress resistance in plants.^[48] Ascorbic acid is present at high levels in all parts of plants and can reach concentrations of 20 millimolar in chloroplasts.^[49]

Glutathione

The free radical mechanism of lipid peroxidation.

Glutathione is a cysteine-containing peptide found in most forms of aerobic life.^[50] It is not required in the diet and is instead synthesized in cells from its constituent amino acids.^[51] Glutathione has antioxidant properties since the thiol group in its cysteine moiety is a reducing agent and can be reversibly oxidized and reduced. In cells, glutathione is maintained in the reduced form by the enzyme glutathione reductase and in turn reduces other metabolites and enzyme systems, such as ascorbate in the glutathione-ascorbate cycle, glutathione peroxidases and glutaredoxins, as well as reacting directly with oxidants.^[45] Due to its high concentration and its central role in maintaining the cell’s redox state, glutathione is one of the most important cellular antioxidants.^[50] In some organisms glutathione is replaced by other thiols, such as by mycothiol in the Actinomycetes, or by trypanothione in the Kinetoplastids.^[52][53]

Melatonin

Melatonin is a powerful antioxidant that can easily cross cell membranes and the blood-brain barrier.^[54] Unlike other antioxidants, melatonin does not undergo redox cycling, which is the ability of a molecule to undergo repeated reduction and oxidation. Redox cycling may allow other antioxidants (such as vitamin C) to act as pro-oxidants and promote free radical formation. Melatonin, once oxidized, cannot be reduced to its former state because it forms several stable end-products upon reacting with free radicals. Therefore, it has been referred to as a terminal (or suicidal) antioxidant.^[55]

Tocopherols and tocotrienols (vitamin E)

Vitamin E is the collective name for a set of eight related tocopherols and tocotrienols, which are fat-soluble vitamins with antioxidant properties.^[56][57] Of these, α-tocopherol has been most studied as it has the highest bioavailability, with the body preferentially absorbing and metabolising this form.^[58]

It has been claimed that the α-tocopherol form is the most important lipid-soluble antioxidant, and that it protects membranes from oxidation by reacting with lipid radicals produced in the lipid peroxidation chain reaction.^[56][59] This removes the free radical intermediates and prevents the propagation reaction from continuing. This reaction produces oxidised α-tocopheroxyl radicals that can be recycled back to the active reduced form through reduction by other antioxidants, such as ascorbate, retinol or ubiquinol.^[60] This is in line with findings showing that α-tocopherol, but not water-soluble antioxidants, efficiently protects glutathione peroxidase 4 (GPX4)-deficient cells from cell death^[61]. GPx4 is the only known enzyme that efficiently reduces lipid-hydroperoxides within biological membranes.

However, the roles and importance of the various forms of vitamin E are presently unclear,^[62][63] and it has even been suggested that the most important function of α-tocopherol is as a signaling molecule, with this molecule having no significant role in antioxidant metabolism.^[64][65] The functions of the other forms of vitamin E are even less well-understood, although γ-tocopherol is a nucleophile that may react with electrophilic mutagens,^[58] and tocotrienols may be important in protecting neurons from damage.^[66]

Pro-oxidant activities

Antioxidants that are reducing agents can also act as pro-oxidants. For example, vitamin C has antioxidant activity when it reduces oxidizing substances such as hydrogen peroxide,^[67] however, it will also reduce metal ions that generate free radicals through the Fenton reaction.^[68][69]

2 Fe³⁺ + Ascorbate → 2 Fe²⁺ + Dehydroascorbate

2 Fe²⁺ + 2 H₂O₂ → 2 Fe³⁺ + 2 OH· + 2 OH⁻

The relative importance of the antioxidant and pro-oxidant activities of antioxidants are an area of current research, but vitamin C, for example, appears to have a mostly antioxidant action in the body.^[68][70] However, less data is available for other dietary antioxidants, such as vitamin E,^[71] or the polyphenols.^[72]

Enzyme systems

Enzymatic pathway for detoxification of reactive oxygen species.

Overview

As with the chemical antioxidants, cells are protected against oxidative stress by an interacting network of antioxidant enzymes.^[1][9] Here, the superoxide released by processes such as oxidative phosphorylation is first converted to hydrogen peroxide and then further reduced to give water. This detoxification pathway is the result of multiple enzymes, with superoxide dismutases catalysing the first step and then catalases and various peroxidases removing hydrogen peroxide. As with antioxidant metabolites, the contributions of these enzymes to antioxidant defenses can be hard to separate from one another, but the generation of transgenic mice lacking just one antioxidant enzyme can be informative.^[73]

Superoxide dismutase, catalase and peroxiredoxins

Superoxide dismutases (SODs) are a class of closely related enzymes that catalyse the breakdown of the superoxide anion into oxygen and hydrogen peroxide.^[74][75] SOD enzymes are present in almost all aerobic cells and in extracellular fluids.^[76] Superoxide dismutase enzymes contain metal ion cofactors that, depending on the isozyme, can be copper, zinc, manganese or iron. In humans, the copper/zinc SOD is present in the cytosol, while manganese SOD is present in the mitochondrion.^[75] There also exists a third form of SOD in extracellular fluids, which contains copper and zinc in its active sites.^[77] The mitochondrial isozyme seems to be the most biologically important of these three, since mice lacking this enzyme die soon after birth.^[78] In contrast, the mice lacking copper/zinc SOD (Sod1) are viable but have numerous pathologies and a reduced lifespan (see article on superoxide), while mice without the extracellular SOD have minimal defects (sensitive to hyperoxia).^[73][79] In plants, SOD isozymes are present in the cytosol and mitochondria, with an iron SOD found in chloroplasts that is absent from vertebrates and yeast.^[80]

Catalases are enzymes that catalyse the conversion of hydrogen peroxide to water and oxygen, using either an iron or manganese cofactor.^[81][82] This protein is localized to peroxisomes in most eukaryotic cells.^[83] Catalase is an unusual enzyme since, although hydrogen peroxide is its only substrate, it follows a ping-pong mechanism. Here, its cofactor is oxidised by one molecule of hydrogen peroxide and then regenerated by transferring the bound oxygen to a second molecule of substrate.^[84] Despite its apparent importance in hydrogen peroxide removal, humans with genetic deficiency of catalase — “acatalasemia” — or mice genetically engineered to lack catalase completely, suffer few ill effects.^[85][86]

Decameric structure of AhpC, a bacterial 2-cysteine peroxiredoxin from Salmonella typhimurium.^[87]

Peroxiredoxins are peroxidases that catalyze the reduction of hydrogen peroxide, organic hydroperoxides, as well as peroxynitrite.^[88] They are divided into three classes: typical 2-cysteine peroxiredoxins; atypical 2-cysteine peroxiredoxins; and 1-cysteine peroxiredoxins.^[89] These enzymes share the same basic catalytic mechanism, in which a redox-active cysteine (the peroxidatic cysteine) in the active site is oxidized to a sulfenic acid by the peroxide substrate.^[90] Over-oxidation of this cysteine residue in peroxiredoxins inactivates these enzymes, but this can be reversed by the action of sulfiredoxin.^[91] Peroxiredoxins seem to be important in antioxidant metabolism, as mice lacking peroxiredoxin 1 or 2 have shortened lifespan and suffer from hemolytic anaemia, while plants use peroxiredoxins to remove hydrogen peroxide generated in chloroplasts.^[92][93][94]

Thioredoxin and glutathione systems

The thioredoxin system contains the 12-kDa protein thioredoxin and its companion thioredoxin reductase.^[95] Proteins related to thioredoxin are present in all sequenced organisms with plants, such as Arabidopsis thaliana, having a particularly great diversity of isoforms.^[96] The active site of thioredoxin consists of two neighboring cysteines, as part of a highly conserved CXXC motif, that can cycle between an active dithiol form (reduced) and an oxidized disulfide form. In its active state, thioredoxin acts as an efficient reducing agent, scavenging reactive oxygen species and maintaining other proteins in their reduced state.^[97] After being oxidized, the active thioredoxin is regenerated by the action of thioredoxin reductase, using NADPH as an electron donor.^[98]

The glutathione system includes glutathione, glutathione reductase, glutathione peroxidases and glutathione S-transferases.^[50] This system is found in animals, plants and microorganisms.^[50][99] Glutathione peroxidase is an enzyme containing four selenium-cofactors that catalyzes the breakdown of hydrogen peroxide and organic hydroperoxides. There are at least four different glutathione peroxidase isozymes in animals.^[100] Glutathione peroxidase 1 is the most abundant and is a very efficient scavenger of hydrogen peroxide, while glutathione peroxidase 4 is most active with lipid hydroperoxides. Surprisingly, glutathione peroxidase 1 is dispensable, as mice lacking this enzyme have normal lifespans,^[101] but they are hypersensitive to induced oxidative stress.^[102] In addition, the glutathione S-transferases show high activity with lipid peroxides.^[103] These enzymes are at particularly high levels in the liver and also serve in detoxification metabolism.^[104]

Oxidative stress in disease

Oxidative stress is thought to contribute to the development of a wide range of diseases including Alzheimer’s disease,^[105][106] Parkinson’s disease,^[107] the pathologies caused by diabetes,^[108][109] rheumatoid arthritis,^[110] and neurodegeneration in motor neurone diseases.^[111] In many of these cases, it is unclear if oxidants trigger the disease, or if they are produced as a secondary consequence of the disease and from general tissue damage;^[12] One case in which this link is particularly well-understood is the role of oxidative stress in cardiovascular disease. Here, low density lipoprotein (LDL) oxidation appears to trigger the process of atherogenesis, which results in atherosclerosis, and finally cardiovascular disease.^[112][113]

A low calorie diet extends median and maximum lifespan in many animals. This effect may involve a reduction in oxidative stress.^[114] While there is some evidence to support the role of oxidative stress in aging in model organisms such as Drosophila melanogaster and Caenorhabditis elegans,^[115][116] the evidence in mammals is less clear.^{[117][118][119]} Diets high in fruit and vegetables, which are high in antioxidants, promote health and reduce the effects of aging, however antioxidant vitamin supplementation has no detectable effect on the aging process, so the effects of fruit and vegetables may be unrelated to their antioxidant contents.^[120][121] One reason for this might be the fact that consuming antioxidant molecules such as polyphenols and vitamin E will produce changes in other parts of metabolism, so it may be these other non-antioxidant effects that are the real reason they are important in human nutrition.^[64][122]

Health effects

Disease treatment

The brain is uniquely vulnerable to oxidative injury, due to its high metabolic rate and elevated levels of polyunsaturated lipids, the target of lipid peroxidation.^[123] Consequently, antioxidants are commonly used as medications to treat various forms of brain injury. Here, superoxide dismutase mimetics,^[124] sodium thiopental and propofol are used to treat reperfusion injury and traumatic brain injury,^[125] while the experimental drug NXY-059^[126][127] and ebselen^[128] are being applied in the treatment of stroke. These compounds appear to prevent oxidative stress in neurons and prevent apoptosis and neurological damage. Antioxidants are also being investigated as possible treatments for neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis,^[129][130] and as a way to prevent noise-induced hearing loss.^[131]

Disease prevention

Structure of the polyphenol antioxidant resveratrol.

Antioxidants can cancel out the cell-damaging effects of free radicals.^[1] Furthermore, people who eat fruits and vegetables, which happen to be good sources of antioxidants, have a lower risk of heart disease and some neurological diseases,^[132] and there is evidence that some types of vegetables, and fruits in general, protect against a number of cancers.^[133] These observations suggested the idea that antioxidants might help prevent these conditions. However, this hypothesis has now been tested in many clinical trials and does not seem to be true, since antioxidant supplements have no clear effect on the risk of chronic diseases such as cancer and heart disease.^[132][134] This suggests that other substances in fruit and vegetables (possibly flavonoids), or a complex mix of substances, may contribute to the better cardiovascular health of those who consume more fruit and vegetables.^[135][136] However, there is some evidence that antioxidants might help prevent other diseases such as macular degeneration,^[137] suppressed immunity due to poor nutrition,^[138] and neurodegeneration.^[139]

It is thought that oxidation of low density lipoprotein in the blood contributes to heart disease, and initial observational studies found that people taking Vitamin E supplements had a lower risk of developing heart disease.^[140] Consequently, at least seven large clinical trials were conducted to test the effects of antioxidant supplement with Vitamin E, in doses ranging from 50 to 600 mg per day. However, none of these trials found a statistically significant effect of Vitamin E on overall number of deaths or on deaths due to heart disease.^[141] Further studies have also been negative.^[142][143] It is not clear if the doses used in these trials or in most dietary supplements are capable of producing any significant decrease in oxidative stress.^[144] Overall, despite the clear role of oxidative stress in cardiovascular disease, controlled studies using antioxidant vitamins have observed no reduction in either the risk of developing heart disease, or the rate of progression of existing disease.^[145][146]

While several trials have investigated supplements with high doses of antioxidants, the “Supplémentation en Vitamines et Mineraux Antioxydants” (SU.VI.MAX) study tested the effect of supplementation with doses comparable to those in a healthy diet.^[147] Over 12,500 French men and women took either low-dose antioxidants (120 mg of ascorbic acid, 30 mg of vitamin E, 6 mg of beta carotene, 100 μg of selenium, and 20 mg of zinc) or placebo pills for an average of 7.5 years. The investigators found there was no statistically significant effect of the antioxidants on overall survival, cancer, or heart disease. However, in a post-hoc analysis they found a 31% reduction in the risk of cancer in men, but not women.

Many nutraceutical and health food companies sell formulations of antioxidants as dietary supplements and these are widely used in industrialized countries.^[148] These supplements may include specific antioxidant chemicals, like resveratrol (from grape seeds or knotweed roots),^[149] combinations of antioxidants, like the “ACES” products that contain beta carotene (provitamin A), vitamin C, vitamin E and Selenium, or herbs that contain antioxidants – such as green tea and jiaogulan. Although some levels of antioxidant vitamins and minerals in the diet are required for good health, there is considerable doubt as to whether these antioxidant supplements are beneficial or harmful, and if they are actually beneficial, which antioxidant(s) are needed and in what amounts.^{[132][134][150]} Indeed, some authors argue that the hypothesis that antioxidants could prevent chronic diseases has now been disproven and that the idea was misguided from the beginning.^[151]

For overall life expectancy, it has even been suggested that moderate levels of oxidative stress may increase lifespan in the worm Caenorhabditis elegans, by inducing a protective response to increased levels of reactive oxygen species.^[152] However, the suggestion that increased life expectancy comes from increased oxidative stress conflicts with results seen in the yeast Saccharomyces cerevisiae,^[153] and the situation in mammals is even less clear.^{[117][118][119]} Nevertheless, antioxidant supplements do not appear to increase life expectancy in humans.^[154]

Physical exercise

During exercise, oxygen consumption can increase by a factor of more than 10.^[155] This leads to a large increase in the production of oxidants and results in damage that contributes to muscular fatigue during and after exercise. The inflammatory response that occurs after strenuous exercise is also associated with oxidative stress, especially in the 24 hours after an exercise session. The immune system response to the damage done by exercise peaks 2 to 7 days after exercise, which is the period during which most of the adaptation that leads to greater fitness occurs. During this process, free radicals are produced by neutrophils to remove damaged tissue. As a result, excessive antioxidant levels may inhibit recovery and adaptation mechanisms.^[156] Antioxidant supplements may also prevent any of the health gains that normally come from exercise, such as increased insulin sensitivity.^[157]

The evidence for benefits from antioxidant supplementation in vigorous exercise is mixed. There is strong evidence that one of the adaptations resulting from exercise is a strengthening of the body’s antioxidant defenses, particularly the glutathione system, to regulate the increased oxidative stress.^[158] This effect may be to some extent protective against diseases which are associated with oxidative stress, which would provide a partial explanation for the lower incidence of major diseases and better health of those who undertake regular exercise.^[159]

However, no benefits for physical performance to athletes are seen with vitamin E supplementation.^[160] Indeed, despite its key role in preventing lipid membrane peroxidation, 6 weeks of vitamin E supplementation had no effect on muscle damage in ultramarathon runners.^[161] Although there appears to be no increased requirement for vitamin C in athletes, there is some evidence that vitamin C supplementation increased the amount of intense exercise that can be done and vitamin C supplementation before strenuous exercise may reduce the amount of muscle damage.^[162][163] However, other studies found no such effects, and some research suggests that supplementation with amounts as high as 1000 mg inhibits recovery.^[164]

Adverse effects

Structure of the metal chelator phytic acid.

Relatively strong reducing acids can have antinutrient effects by binding to dietary minerals such as iron and zinc in the gastrointestinal tract and preventing them from being absorbed.^[165] Notable examples are oxalic acid, tannins and phytic acid, which are high in plant-based diets.^[166] Calcium and iron deficiencies are not uncommon in diets in developing countries where less meat is eaten and there is high consumption of phytic acid from beans and unleavened whole grain bread.^[167]

Nonpolar antioxidants such as eugenol—a major component of oil of cloves—have toxicity limits that can be exceeded with the misuse of undiluted essential oils.^[171] Toxicity associated with high doses of water-soluble antioxidants such as ascorbic acid are less of a concern, as these compounds can be excreted rapidly in urine.^[172] More seriously, very high doses of some antioxidants may have harmful long-term effects. The beta-Carotene and Retinol Efficacy Trial (CARET) study of lung cancer patients found that smokers given supplements containing beta-carotene and vitamin A had increased rates of lung cancer.^[173] Subsequent studies confirmed these adverse effects.^[174]

These harmful effects may also be seen in non-smokers, as a recent meta-analysis including data from approximately 230,000 patients showed that β-carotene, vitamin A or vitamin E supplementation is associated with increased mortality but saw no significant effect from vitamin C.^[175] No health risk was seen when all the randomized controlled studies were examined together, but an increase in mortality was detected only when the high-quality and low-bias risk trials were examined separately. However, as the majority of these low-bias trials dealt with either elderly people, or people already suffering disease, these results may not apply to the general population.^[176] This meta-analysis was later repeated and extended by the same authors, with the new analysis published by the Cochrane Collaboration; confirming the previous results.^[177] These two publications are consistent with some previous meta-analyzes that also suggested that Vitamin E supplementation increased mortality,^[178] and that antioxidant supplements increased the risk of colon cancer.^[179] However, the results of this meta-analysis are inconsistent with other studies such as the SU.VI.MAX trial, which suggested that antioxidants have no effect on cause-all mortality.^{[147][180][181][182]} Overall, the large number of clinical trials carried out on antioxidant supplements suggest that either these products have no effect on health, or that they cause a small increase in mortality in elderly or vulnerable populations.^{[132][134][175]}

While antioxidant supplementation is widely used in attempts to prevent the development of cancer, it has been proposed that antioxidants may, paradoxically, interfere with cancer treatments.^[183] This was thought to occur since the environment of cancer cells causes high levels of oxidative stress, making these cells more susceptible to the further oxidative stress induced by treatments. As a result, by reducing the redox stress in cancer cells, antioxidant supplements could decrease the effectiveness of radiotherapy and chemotherapy.^[184][185] However, the evidence is mixed, and some reviews indicate that antioxidants could reduce side effects or increase survival times.^[186][187]

Measurement and levels in food

Fruits and vegetables are good sources of antioxidants.

Measurement of antioxidants is not a straightforward process, as this is a diverse group of compounds with different reactivities to different reactive oxygen species. In food science, the oxygen radical absorbance capacity (ORAC) has become the current industry standard for assessing antioxidant strength of whole foods, juices and food additives.^[188][189] Other measurement tests include the Folin-Ciocalteu reagent, and the Trolox equivalent antioxidant capacity assay.^[190] The CAP-e assay measures antioxidants that are available to enter and protect live cells.^[191]

Antioxidants are found in varying amounts in foods such as vegetables, fruits, grain cereals, eggs, meat, legumes and nuts. Some antioxidants such as lycopene and ascorbic acid can be destroyed by long-term storage or prolonged cooking.^[192][193] Other antioxidant compounds are more stable, such as the polyphenolic antioxidants in foods such as whole-wheat cereals and tea.^[194][195] The effects of cooking and food processing are complex, as these processes can also increase the bioavailability of antioxidants, such as some carotenoids in vegetables.^[196] In general, processed foods contain fewer antioxidants than fresh and uncooked foods, since the preparation processes may expose the food to oxygen.^[197]

Other antioxidants are not vitamins and are instead made in the body. For example, ubiquinol (coenzyme Q) is poorly absorbed from the gut and is made in humans through the mevalonate pathway.^[42] Another example is glutathione, which is made from amino acids. As any glutathione in the gut is broken down to free cysteine, glycine and glutamic acid before being absorbed, even large oral doses have little effect on the concentration of glutathione in the body.^[201][202] Although large amounts of sulfur-containing amino acids such as acetylcysteine can increase glutathione,^[203] no evidence exists that eating high levels of these glutathione precursors is beneficial for healthy adults.^[204] Supplying more of these precursors may be useful as part of the treatment of some diseases, such as acute respiratory distress syndrome, protein-energy malnutrition, or preventing the liver damage produced by paracetamol overdose.^[203][205]

Other compounds in the diet can alter the levels of antioxidants by acting as pro-oxidants. Here, consuming the compound causes oxidative stress, which the body responds to by inducing higher levels of antioxidant defenses such as antioxidant enzymes.^[151] Some of these compounds, such as isothiocyanates and curcumin, may be chemopreventive agents that either block the transformation of abnormal cells into cancerous cells, or even kill existing cancer cells.^[151][206]

Uses in technology

Food preservatives

Antioxidants are used as food additives to help guard against food deterioration. Exposure to oxygen and sunlight are the two main factors in the oxidation of food, so food is preserved by keeping in the dark and sealing it in containers or even coating it in wax, as with cucumbers. However, as oxygen is also important for plant respiration, storing plant materials in anaerobic conditions produces unpleasant flavors and unappealing colors.^[207] Consequently, packaging of fresh fruits and vegetables contains an ~8% oxygen atmosphere. Antioxidants are an especially important class of preservatives as, unlike bacterial or fungal spoilage, oxidation reactions still occur relatively rapidly in frozen or refrigerated food.^[208] These preservatives include natural antioxidants such as ascorbic acid (AA, E300) and tocopherols (E306), as well as synthetic antioxidants such as propyl gallate (PG, E310), tertiary butylhydroquinone (TBHQ), butylated hydroxyanisole (BHA, E320) and butylated hydroxytoluene (BHT, E321).^[209][210]

The most common molecules attacked by oxidation are unsaturated fats; oxidation causes them to turn rancid.^[211] Since oxidized lipids are often discolored and usually have unpleasant tastes such as metallic or sulfurous flavors, it is important to avoid oxidation in fat-rich foods. Thus, these foods are rarely preserved by drying; instead, they are preserved by smoking, salting or fermenting. Even less fatty foods such as fruits are sprayed with sulfurous antioxidants prior to air drying. Oxidation is often catalyzed by metals, which is why fats such as butter should never be wrapped in aluminium foil or kept in metal containers. Some fatty foods such as olive oil are partially protected from oxidation by their natural content of antioxidants, but remain sensitive to photooxidation.^[212] Antioxidant preservatives are also added to fat-based cosmetics such as lipstick and moisturizers to prevent rancidity.

Industrial uses

Antioxidants are frequently added to industrial products. A common use is as stabilizers in fuels and lubricants to prevent oxidation, and in gasolines to prevent the polymerization that leads to the formation of engine-fouling residues.^[213]

They are widely used to prevent the oxidative degradation of polymers such as rubbers, plastics and adhesives that causes a loss of strength and flexibility in these materials.^[214] Polymers containing double bonds in their main chains are especially susceptible to oxidation and ozonolysis. Solid polymer products start to crack on exposed surfaces as the material degrades and the chains unzip. The mode of cracking varies between oxygen and ozone attack, the former causing a “crazy paving” effect, while ozone attack produces deeper cracks aligned at right angles to the tensile strain in the product. Ozone cracking is especially damaging to elastomers such as natural rubber, polybutadiene and other double-bonded rubbers. They can be protected by antiozonants. Oxidation and UV degradation are also frequently linked, mainly because UV radiation creates free radicals by bond breakage. The free radicals then react with oxygen to produce peroxy radicals which cause yet further damage, often in a chain reaction. Other polymers suceptible to oxidation include polypropylene and polyethylene. The former is more sensitive owing to the presence of secondary carbon atoms present in every repeat unit. Attack occurs at this point because the free radical formed is more stable than one formed on a primary carbon atom. Oxidation of polyethylene tends to occur at weak links in the chain, such as branch points in low density polyethylene.

References and Further reading

• Nick Lane Oxygen: The Molecule That Made the World (Oxford University Press, 2003) ISBN 0-198-60783-0
• Barry Halliwell and John M.C. Gutteridge Free Radicals in Biology and Medicine(Oxford University Press, 2007) ISBN 0-198-56869-X
• Jan Pokorny, Nelly Yanishlieva and Michael H. Gordon Antioxidants in Food: Practical Applications (CRC Press Inc, 2001) ISBN 0-849-31222-1

Tuhan menciptakan manusia sebagai makhluk yang paling sempurna. TUbuh manusia dilengkapi dengan kemampuan alamiah untuk menyembuhkan dirinya sendiri (self healing power) manakala terganggu kesehatannya.

Tuhan juga menciptakan makhluk lai
n seperti hewan, tumbuh-tumbuhan, udara, air, tanah, dan lain-lain bagi manusia agar kita bisa bertahan hidup, menikmati hidup, dan terus berkembang. Kemudian, sang Maha Pencipta memerintahkan manusia supaya hidup selaras dengan alam dan mematuhi hukum-hukum alam. Di sisi lain, keserakahan dan kesombongan adalah sifat dasar dari manusia, yang membuat manusia menjadi berani melawan dan merusak alam, tak mau lagi hidup harmonis selaras dengan alam. Termasuk dalam hal ini ialah TIDAK HARMONIS Dengan DIRINYA, TUBUHNYA SENDIRI.i

Akibatnya, alam murka dan terjadilah berbagai bencana alam, muncullah berbagai penyakit, virus-virus jenis baru yang dahulu belum pernah ada, sebagai konsekuensi memilih gaya hidup yang ceroboh’ seenaknya sendiri, tak ramah lingkungan, manjauhi cara-cara alamiah dalam menjalani kehidupannya.

Agar pulih dari sakitnya, manusia kini menggantungkan dirinya pada obat-obatan kimia/medis dari dokter ataupun yang dijual bebas di pasaran. Atau justru terjembab dalam praktek-praktek klenik dan tahayul yang bersifat syirik. Manusia sudah lupa akan kodratnya, pada kekuatan alamiahnya sendiri.

Hanya sedikit manusia yang mulai menyadari kesalahannya dan mau belajar, membuka hatinya guna mencari jalan yang selaras dengan alam untuk mendapatkan kembali kebahagiaan hidup dan kesehatannya.

Beberapa pakar / praktisi kesehatan telah mendapatkan pencerahan dan memberikan petunjuk tentang cara-cara penyembuhan dan hidup sehat selaras dengan alam.

Namun, ternyata para penderita/pasien maupun umumnya masyarakat kini BANYAK. Yang BINGUNG, bahkan tak jarang banyak yang tersesat dalam mengikuti saran-saran dan petunjuk dari para pakar tersebut. Pendapat seorang pakar b
isa BERLAWANAN dengan pendapat pakar yang lain tentang suatu masalah kesehatan yang sama!

Sebagai contoh konkret, dr. Tan Shot Yen yang populer, dalam rubrik Konsultasi Nutrisi di tabloid Nyata bulan Juli 2009 menulis bahwa dia tidak percaya dengan diet menurut golongan darah. Padahal jutaan orang di penjuru dunia (termasuk saya) telah banyak memetik manfaat dan kesembuhan dengan mengikuti diet golongan darah! Saya mengjhormati dr. Tan maupun Dr. Peter D’Adamo. Dalam hal ini, menurut hemat saya dr. Tan akan lebih bijaksana jika mempelajari lebih dalam tulisan-tulisan dan temuan-temuan mutakhir dr. D”Adamo yang sangat bermutu dan komprehensif dalam membahas nutrisi. Ya, sejujirnya Dr. D”Adamo lebih pantas sebagai gurunya dr. Tan.

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Berangkat dari pengalaman hidup saya selama ini, dimana saya pernah menderita penyakit batu ginjal 2 kali! Yaitu pada tahun 1994 (saat berusia 28 tahun) dan tahun 2007 (usia 41 tahun). Selain itu saya juga telah mengalami operasi pengambilan amandel dan usus buntu saat remaja. Sejak itulah maka saya menetapkan misi pribadi saya untuk menjadi Pemerhati Kesehatan, paling tidak untuk menjawab pertanyaan-pertanyaan besar mengenai “penderitaan” yang pernah saya alami dan yang saya lihat terjadi pada keluarga maupun teman-teman saya.

Yah, saya selalu mencari informasi terbaru & paking mutakhir tentang dunia kesehatan melalui berbagai media dan internet. Dan akhirnya, bagian terpenting dari jawaban yang senantiasa saya cari itu kini terungkap! Syukur Alhamdulillah. Dan misi selanjutnya adalah membagikan info-info tentang kesehatan kepada masyarakat di tanah air dan kepada dunia.

Saya berani menjamin bahwa, insyaallah, info-info kesehatan dari saya adalah sangat berani/ vokal, bermutu tinggi, sangat bisa dipercaya, sangat obyektif, dan sangat bermanfaat bagi Anda semua. Terutama bagi Anda yang ingin mendapatkan kesembuhan dari penyakit yang diderita atau yang ingin menjaga kesehatan & daya tahan tubuh (immune system). Mungkin info-info tersebut  nantinya nampak kontroversial, tidak umum, dan “bikin muka merah” bagi pakar-pakar kesehatan sperti dokter, ahli gaizi, praktisi alternatif, industri farmasi dan sebagainya. Namun, saya lebih membela kepentingan masyarakat konsumen dan pasien. Ulasan dari saya tidak akan teoritis belaka, karena berdasarkan praktik-praktik yang saya terapkan sendiri sehingga saya menjadi sehat secara alamiah, tanpa dokter & obat-obatan.

Bukan rahasia bahwa umumnya masyarakat (seperti saya dulu) telah lama mengalami kebingungan (atau, maaf, kebodohan) tentang seluk beluk dunia kesehatan. Tak hanya di Indonesia, tapi juga di USA dan Eropa sama saja! Kenapa? Karena mindset mereka telah salah/salah kaprah disebabkan doktrin-doktrin tentang kesehatan dari para pakar kesehatan, institusi-institusi pemerintah maupun swasta dan industri farmasi. Terutama iklan-iklan obat (kimia), multivitamin, praktek penyebuhan di TV, radio, koran, internet dan lain-lain. Kebenaran sejati tentang kesehatan sepertinnya sengaja disimpan demi kepentingan pihak-pihak tertentu!

Itulah sebabnya kini banyak timbul berbagai macam penyakit baru yang dulu tidak ada, seperti: HIV/Aids, flu burung, flu babi dan lain-lain. Kasus-kasus batu ginjal, gagal ginjal, diabetes, stroke meninkat drastis, bahkan terjadi di usia muda (belasan tahun). Intinya hanya satu: manusia makin menjauhi alam, tak ramah pada alam, dan menerapkan gaya hidup yang makin tak alamiah sehingga kini alam berbalik murka kepada manusia! Satu-satunya jalan: kembalilah kepada alam. Tak ada jalan lain.

Saya akan mengungkapkan fakta versus mitos tentang kesehatan yang belum pernah diungkapkan oleh para pakar kesehatan sekalipun secara gamblang dan mudah dimengerti oleh orang awam, serta memihak kepada kepentingan masyarakat, tanpa ada sponsor dari pihak manapun.

Tunggulah ulasan-ulasan saya pada blog berikutnya.

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