Researchers establish how citrus fruits inhibit cancer, cholesterol

Guardian Newspapers 14.4.05

Fresh studies have shown how natural substances in citrus fruits- orange, grapefruit and tangerine- help fight cancer, common cold, heart disease, obesity, iron deficiency, birth defects, and 'bad' cholesterol, reports CHUKWUMA MUANYA.

INCORPORATING plenty of citrus fruits such as oranges, tangerine and grapefruit in the daily diet plan may offer another important yet lesser known nutritional bonus: citrus limonoids.

A recent study published last week shows that citrus limonoids help fight cancers of the mouth, skin, lung, breast, stomach and colon in laboratory tests with animals and with human cells.

Studies have further shown that limonoids inhibit the development of cancer in laboratory animals and in human breast cancer cells as well as reducing cholesterol.

Researchers have also suggested that, if ingested, limonoids may not be absorbed in the large intestine, and therefore could be distributed throughout the body, with beneficial effects.

Previous studies show that citrus fruits hold promise for certain childhood cancers. Experts suggest that the popular citrus drink could become a cocktail to prevent or stop the deadly diseases in humans. It has also been shown that orange and tangerine peels could be better than drugs for lowering cholesterol.

Other studies indicate that naturally occurring substances in citrus juices, called flavonoids, show promise against prostate cancer, lung cancer and melanoma in laboratory studies.

Agricultural Research Service scientists in northern California, United States, led by a chemist, Gary D. Manners, are uncovering new details about these compounds. Manners and co-investigators have reported their findings in studies published during the past several years. They have demonstrated, for example, that each time one bites into a citrus slice or drink a glass of orange juice, the body can readily access a limonoid called limonin. The team was the first to show limonin's "bio-availability."

According to a botanist at the University of Lagos, Akoka, Dr Dotun Adekunle, in citrus species, limonoids are produced in leaves and transported to fruit and seeds, with limonoid concentration highest in the earliest stages of growth of leaves and fruit and highest in seeds during fruit growth and maturation.

He explained: "In leaves and fruit, total limonoid content increases during growth and maturation and decreases after maturation. In contrast, limonoid concentration does not decrease in seeds after fruit maturity, indicating that seeds act as storage tissues for these compounds. Interestingly, grapefruit seeds have a higher limonoid concentration on a weight basis than orange and lemon seeds."

Indeed, eating plenty of oranges and other citrus fruits can boost the level of rutin, a bioflavonoid that was singled out by researchers in the 1950s as one that could help strengthen fragile capillaries and minimise the bruising that often accompanies this condition.

"It is important to remember, however, that though this compound may prevent some bruises from occurring, it is not good for the treatment of a bruise after it has occurred," says Mrs A Ajayi, of the Department of Pharmacognosy Faculty of Pharmacy at the College of Medicine, University of Lagos (CMUL), Idi-Araba.

A nutritionist at the Nigerian Institute of Medical Research (NIMR), Yaba, Lagos, Dr Rosemary Anyanwu, told The Guardian that the body derives limonin from a parent compound--limonin glycoside-that is present in citrus and citrus juices in about the same amount as Vitamin C.

In other early work, Manners and colleagues found that limonin may lower cholesterol. The researchers showed that, when exposed to limonin, human liver cells in petri dishes produced less apo B, a compound associated with higher cholesterol levels. High cholesterol levels are linked to increase risk of heart disease and other health problems.

According to Dr Chinyere Ogbonna of Ugo Health Services, Festac Town, Lagos, citrus fruits like oranges, tangerine and grapefruits have important nutritional benefits. They are a natural source of potassium, and are sodium and cholesterol-free.

She said: "Vitamin C (or ascorbic acid) is one of the most important vitamins found in citrus fruits. Folate is a B vitamin that plays several roles in the body. It is important for mature red-blood cell production and guards against anaemia. Sufficient folate in the diet is also critical to preventing neural-tube defects in a developing foetus.

"Potassium, an essential mineral, is abundant in some citrus fruits, especially oranges. Potassium works to maintain fluid balance in the body and nerve transmission. Dehydration and consumption of diuretics (such as coffee and tea) are two of the more common factors contributing to potassium deficiency.

"In addition, potassium plays a key role in lowering blood pressure, which decreases the risk of both heart attacks and strokes. As long as you eat a well-balanced diet, including potassium-rich vegetables and fruits like oranges and tomatoes, there's little concern. However, people taking diuretics in the treatment of hypertension may be at risk of potassium deficiency and these people might need to supplement."

Citrus fruits have also been shown to be a good source of dietary fibre, including soluble fibre. Fibre reportedly aids in digestion and elimination and may help reduce blood cholesterol levels and the risk of certain forms of cancer.

Consuming citrus foods like orange and grapefruit have been shown to help boost the absorption of non-haem iron (the iron found in plants - not meat products). "What this means is that if you drink a glass of orange juice before you eat a spinach salad - your body absorbs much more iron from the spinach, therefore combating anaemia," Ogbonna said.

According to recent research, a low-fat diet rich in fruits and vegetables like citrus fruit and their juices, may help fight against heart disease.

Dr Kayode Akinlade, secretary general Nigeria Medical Association (NMA) said: "The high level of soluble fibre found in citrus fruits helps to maintain healthy cholesterol levels. Remember, citrus fruits are fat- and cholesterol-free and the antioxidant activity of Vitamin C mops up the aggressive 'free radicals' before they cause damage that leads to cardiovascular disease. Recent research points towards the fact that folate may also play a role in the prevention of heart disease and certain cancers."

Gynaecologists say women of childbearing age can dramatically reduce the risk of having a child with these birth defects by consuming plenty of citrus fruits and dark green leafy vegetables, especially fluted pumpkin leaves (ugu), amaranth, spinach, asparagus and broccoli to meet adequate levels of folate.

According to Dr Ralph Omaliko of MayFair Hospital, Onitsha, "the difficult part is that the neural tube closes by 28 days of gestation, before most women realise they are pregnant. That is why it is important that women of childbearing age consume adequate daily levels of folate before, and soon after, they become pregnant."

It is recommended that people trying to lose weight should consume fruits and vegetables with high fibre and water content - like citrus fruits. According to a Weight Loss therapist, Princess Quincy Ayodele, of Quincy Health Services, Ikeja, Lagos, citrus fruits are low in calories with one medium orange containing about 60 calories per serving. "Citrus fruits actually take the "edge" off your appetite to avoid overeating as they are low glycaemic index foods."

It has long been claimed that Vitamin C is the "miracle cure" for the common cold. The bulk of evidence supports that Vitamin C can reduce the duration and severity of a cold. However, the evidence of whether it can prevent the common cold is not convincing. It has, however, been suggested that Vitamin C may reduce the incidence of colds in some particularly vulnerable segments of the population, such as those with low dietary intakes of Vitamin C.

According to Anyanwu, the findings on citrus is promising not only for its potential to arrest cancer, but because limonoids induce no side affects. "Limonoids are naturally occurring compounds," she said. "Unlike other anti-cancer drugs that are toxic, limonoids apparently do not hurt a person. That is the beautiful potential."

A consultant physician at Optimal Specialist Hospital, Dr Ugochukwu Chukwuneye, calls citrus fruit "a vast reservoir of anti-carcinogens." He said limonoids are unique to citrus. "They are not present in any other fruits or vegetables."

Anyanwu explained that flavonoids and limonoids - nutrient-packed pigments that give colour and taste to fruit - may work against cancer in any of three ways: prevent it from forming, slow the growth of existing cancer, or kill cancer cells. "The limonoids, which differ structurally from flavonoids, seem to do all three," she said.

The researchers found that the neuroblastoma cells died with relatively small amounts of concentrated limonoids and all in 48 hours or less.

A compound found in the peels of citrus fruit has the potential to lower cholesterol more effectively than some prescription drugs, and without side effects, according to a study by U.S. and Canadian researchers.

A joint study by the U.S. Department of Agriculture and KGK Synergise, a Canadian nutraceutical company, identified a class of compounds isolated from orange and tangerine peels that shows promise in animal studies as a potent, natural alternative for lowering Low Density Lipo-protein (LDL) cholesterol (bad cholesterol), without the possible side effects, such as liver disease and muscle weakness, of conventional cholesterol-lowering drugs.

The findings is described in the Journal of Agricultural and Food Chemistry. The compounds, called polymethoxylated flavones (PMFs), are similar to other plant pigments found in citrus fruits that have been increasingly linked to health benefits, including protection against cancer, heart disease and inflammation.

The study is believed to be the first to show that PMFs can lower cholesterol, the researchers say. "Our study has shown that PMFs have the most potent cholesterol-lowering effect of any other citrus flavonoid," says Dr Elzbieta Kurowska, lead investigator of the study and vice president of research at KGK Synergise in Ontario, Canada. "We believe that PMFs have the potential to rival and even beat the cholesterol-lowering effect of some prescription drugs, without the risk of side effects."

PMFs are found in a variety of citrus fruits. The most common citrus PMFs, tangeretin and nobiletin, are found in the peels of tangerines and oranges. They are also found in smaller amounts in the juices of these fruits.

Using hamster models with diet-induced high cholesterol, the researchers showed that feeding them food containing one per cent PMFs lowered levels of LDL cholesterol by 32 to 40 per cent.

Previous animal studies by others have shown that similar flavonoids, particularly hesperidin from oranges and naringin from grapefruit, also may have the ability to lower cholesterol, although not as effectively as PMFs, according to Kurowska.

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