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Mae West once said, 'Too much of a good thing is ...wonderful.' Whatever else she had in mind, it certainly wasn't vitamin A. Although doctors have long known that very large amounts of vitamin A are toxic, studies show that modest doses previously considered safe can increase your risk of fracture.

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What is vitamin A?

Like all vitamins, vitamin A is an organic (carbon-containing) compound that is required to keep the body's metabolism running smoothly. Because the body cannot manufacture vitamins, all 13 must be consumed on a regular basis. Only tiny amounts are required to prevent vitamin-deficiency diseases, but slightly larger amounts of some, such as the B vitamin folic acid, may have additional benefits. But although vitamins are necessary and all-natural, excessive amounts can be harmful.

Along with vitamins D, E, and K, vitamin A is a fat-soluble vitamin. That means it is absorbed into the body with dietary fat, and then stored in the body's own adipose tissue. As a result, you can store enough vitamin A to last for months, but if you take in more than you need, it will slowly build up in your body's tissues. In contrast, the water-soluble vitamins (the B vitamins and vitamin C) are not stored in the body to any appreciable degree; extra amounts are passed into the urine, so toxic reactions occur only if very large amounts are ingested (but deficiencies develop relatively quickly if consumption lags behind need).

First discovered in 1909, vitamin A is also known as retinol and retinoic acid. It is essential for night vision and for healthy skin, hair, nails, and bones. In addition, vitamin A is an antioxidant; it also has an important role in regulating cell growth and development and in maintaining a healthy immune system. The major dietary sources of vitamin A include meat (especially liver), dairy products (especially whole-fat products), eggs, and fortified foods including cereals, low-fat dairy products, and margarine.

Although the body cannot produce vitamin A from scratch, it can convert some from carotenoids, a group of some 600 chemicals that are related to retinol. Beta-carotene and lycopene are the best-known examples of these antioxidants, which are found only in plants. About 8% of the beta-carotene in the diet is converted to vitamin A in the body. The average American man gets about 74% of his vitamin A from meat and dairy products, the remainder from the carotenoids in yellow-orange fruits and vegetables and dark green vegetables. In addition, vitamin A is present in supplements such as multivitamins and fish liver oils.

How much vitamin A is enough? Until 2001, the dietary reference intake for adult men was 5,000 international units (IU) a day, or 1,500 micrograms (mcg). Levels of up to 10,000 IU (3,000 mcg) have been considered safe. Beyond that, though, vitamin A can build up to cause liver damage and brain swelling; pregnant women who ingest too much run the risk of fetal damage. In contrast, apart from yellowish discoloration of the skin, dietary carotenoids seem nontoxic; supplements of beta-carotene, however, increase the risk of lung cancer in male smokers.

Should we all aim to get 5,000 IU of vitamin A each day? Not long ago, the answer was yes — but research has changed that.

Bone building and breakdown

Bone continually undergoes a process of remodeling, which entails resorption and formation. During resorption (A), cells known as osteoclasts attach to the bone surface and break it down, releasing calcium into the blood stream and leaving trenches in the bone (B). Different cells called osteoblasts release collagen into these troughs and eventually evolve into structural bone cells or osteocytes (C). These cells combine with calcium and other minerals to form a cement-like substance known as hydroxyapatite, completing the formation of new bone (D).

Busy bones

To understand the complex way vitamin A affects bones, you need to understand just a bit about bones themselves. Although they are sometimes likened to the steel girders that support tall buildings, your bones are much more complex than passive struts. In fact, bones are vital living tissues that constantly undergo remodeling. Throughout life, bone cells called osteoblasts produce new bones, while osteoclasts resorb and remove old bone. In youth, bone formation outpaces bone resorption; that's why kids grow. In young adulthood, the processes are matched and bones are at their strongest. But with advancing age, bone resorption gains the upper hand. Bones lose calcium and with it, strength. Mild calcium deficiencies produce osteopenia, more advanced deficits, osteoporosis — the 'thin bones' disease. According to a 2004 report from the Surgeon General, roughly 10 million Americans over age 50 have osteoporosis, while another 34 million are at risk for developing it.

Age takes a toll on bones because of changes in the levels of sex hormones, which help keep bones strong. In women, estrogen levels plummet at the time of menopause, while in men above 40 testosterone levels only drift down by about 1% a year. As a result, osteoporosis is very common in women, less prevalent in men.

Other factors also influence bone strength. Diet is very important; a good intake of calcium (1,000 mg a day before age 50, 1,200 mg a day beyond 50) and vitamin D (200 IU a day for ages 19–50, 400 IU a day for ages 51–70, and 600 IU a day thereafter) are crucial. In contrast, high levels of dietary protein increase the loss of calcium in the urine. Excessive amounts of alcohol do the same. Ever the hero, exercise helps keep bones strong — but only weight-bearing and resistance exercises, such as walking and weightlifting, will do the trick.

Until recently, vitamin A was not part of the bone formation vs. bone resorption equation. Then laboratory studies showed that retinoic acid (which the body makes from vitamin A) stimulates osteoclasts but suppresses osteoblasts. That's why even mild excesses of vitamin A appear to increase the risk of fracture. But there's more to it, since a study of men found that a deficiency of vitamin A is also linked to an increased likelihood of fracture.

A-plus fails

The first indication that vitamin A might increase fracture risk came from Scandinavia, where the average vitamin A intake is six times more that it is in southern Europe, and the risk of hip fracture is also much higher. In Norway and Sweden, the study found, people who consumed more than 5,000 IU (1,500 mcg) of vitamin A per day were twice as likely to fracture their hips as people who took in less than 1,666 IU (500 mcg) a day. In fact, a Swedish man is about two times more likely to fracture a hip than is an English woman.

The Nurses' Health Study evaluated vitamin A consumption and fracture risk in 72,337 post-menopausal women. It found that women who averaged more than 10,000 IU (3,000 mcg) of vitamin A per day were one and a half times more likely to fracture their hips than women who consumed less than 4,166 IU (1,250 mcg) a day. The Harvard researchers added the important observation that beta-carotene did not contribute to the risk of fracture.

Women are more vulnerable to osteoporosis than men. Do the Nurses' Health findings apply to men? In Sweden, they do. A year after the Harvard study of women was published, a 30-year study of 2,322 Swedish men found that men with the highest blood levels of vitamin A were 2.5 times more likely to suffer hip fractures and 1.6 times more likely to fracture any bone than men with average blood levels. Although the Swedish study did not evaluate diet per se, it seems likely that men who consume about 5,000 IU (1,500 mcg) a day would boost their blood levels well into the fracture-prone range. That's the old recommended daily intake and is well below the 10,000 IU (3,000 mcg) that has been considered the safe upper limit of daily vitamin A consumption.

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When it comes to vitamin A and bones, more is not better. But is less better?

A-minus fails

The fourth study of vitamin A and fracture risk takes us back across the Atlantic and back to a study of women — in this case to 2,799 50- to 74-year-olds who participated in the first National Health and Nutrition Examination Survey (NHANES I). In the 1970s, the volunteers submitted detailed health information, and the researchers obtained blood samples that were later used to measure vitamin A and beta-carotene levels. The scientists kept track of the women for an average of 22 years. During that time, women with the highest vitamin A levels were 2.1 times more likely to suffer a hip fracture than those with average blood levels of vitamin A. But low levels of the vitamin were almost as hazardous, increasing fracture risk by 1.9 times.

Average gets the A

Moderation may not be the best solution to all problems, but it seems to be the winner in the quest for the best dose of vitamin A. A 4-year study of 958 men and women found that an average daily consumption of 2,000 to 3,000 IU per day (600 to 900 mcg) was associated with the highest bone mineral densities. Unlike the other research, the Rancho Bernardo Study did not evaluate actual factures, but bone density is a good predictor of fracture risk. And in this study, bone density declined in people who took in either more or less vitamin A.

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Vitamin A content of selected foods

Food

Vitamin A (IU)

Vitamin A (mcg)

Beef liver, 3 oz

30,326

9,098

Chicken liver, 3 oz

13,920

4,176

Egg substitute, fortified, ¼ cup

1,356

407

Skim milk, fortified, 1 cup

500

150

Cheese pizza, 1 slice (12' pie)

380

114

Whole milk, 1 cup

306

92

Cheddar cheese, 1 oz

300

90

Whole egg, medium

280

84

Margarine, 1 tbsp

504

151

Butter, 1 tbsp

355

106

Canned salmon, 3 oz

300

90

Yogurt (plain, low-fat), 8 oz

116

35

Fruits and vegetables

No vitamin A, but do contain carotenoids which are partially converted to Vitamin A in the body.

Just right

Taken together, these studies suggest that there is less wiggle room for vitamin A consumption than previously believed. The current recommended daily intake is 3,000 (900 mcg) for men and 2,330 IU (700 mcg) for women. According to the Rancho Bernardo and NHANES I studies, these amounts should be ideal for bones as well as general health. But how can you be sure you are getting the right amount?

It's a bit complex. To avoid excessive amounts, don't eat liver or take fish liver oils. Avoid large amounts of other vitamin A-rich foods such as whole milk, eggs, and meat. Since these foods are not good for cardiovascular health, that's the easy part of the equation. Non-fat dairy products and breakfast cereals are healthful foods, and because they are fortified with vitamin A, they can provide some of what you need (see table above). But a cup of non-fat milk contains only about 500 IU (150 mcg), and a serving of cereal about as much. Try to get much of the extra vitamin A you need from the beta-carotene in yellow-orange vegetables and fruits (carrots, tomatoes, cantaloupe) and in deep-green vegetables such as spinach. If you take multivitamins and other supplements, don't take more than 100% of the daily value for vitamin A (3,000 IU or 900 mcg for men), and look for supplements that provide much of their vitamin A in the form of beta-carotene. And don't forget the other things that keep bones strong, including proper amounts of vitamin D and calcium, and lots of weight-bearing and resistance exercises.

From A to D, nutrition is getting more complex every year. In the case of vitamin A, though, it's also getting smarter.

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