Men with elevated blood levels of vitamin A are more likely to break a bone than men with normal levels, according to a recent study.

The results reflect those of two similar studies in women and have led researchers to say that current levels of vitamin A supplementation and food fortification may need to be reassessed.

The 30-year study involved 2,322 men between the ages of 49 and 51. Men who had the highest blood levels of vitamin A at the study’s start were 1.6 times more likely to break a bone than men who had had an average vitamin A level. Further, men with elevated vitamin A levels had a 2.5 times greater risk than men with lower levels of vitamin A.

Blood levels of beta-carotene, a compound that is converted to vitamin A in the body, did not affect fracture risk.

Vitamin A is important for growth, vision, reproduction and a healthy immune system, however taking too much vitamin A (amounts of 25,000 IU to 50,000 IU per day or more) for prolonged periods can be dangerous. An excess of vitamin A is associated with bone and joint pain, loss of appetite, nausea, vomiting and weight loss. Further, one extremely high dose can cause drowsiness, irritability, headache, vomiting and widespread peeling off of the skin.

Vitamin A is found in fish liver oils, liver, kidney and milk and is sometimes added to dairy products.

Malnourished children are at the greatest risk of vitamin A deficiency, while the elderly are most at risk from too much vitamin A. Researchers suggest that, due to the high life expectancy of Western countries, vitamin A supplementation and food fortification in these areas may be harmful.

The New England Journal of Medicine January 23, 2003;348:287-294,347-349

Developing cells, including bone, are regulated by steroid hormones, that is estrogen, progesterone, cortisol and testosterone, and, most critical, thyroid and vitamins A and D. There is a very delicate balance between these substances, all of which are made in our bodies except vitamins A and D.

Unfortunately in Uppsala, Sweden, greater than 59 degrees north latitude, where the study was done there is little UV-B light. This means that almost all vitamin D must be provided by food such as fatty fish, especially the skin and fat around the tail and fins and fish livers.

Cod liver oil, a popular supplement in northern Europe, contains high levels of vitamin A with relatively little vitamin D.

In the United States, highest latitude about 48 degrees north, lowest latitude 27 degrees north, when cod liver oil or vitamin supplements with the recommended daily allowance of vitamin A (5,000 IU) are combined with sunlight and vitamin D in foods, the vitamins A and D would to some degree match, perhaps, we really don't know and there would be exceptions.

In northern Europe depending on fish intake, and assuming it -- especially the fish fat intake -- has declined, cod liver would be the primary source of vitamin D. It is likely the vitamin A from supplements, animal livers and fish livers, would be higher in relative proportion.

In lower latitude countries, the sun plus cod liver oil (in winter only) would give significant D and some A. Vitamin A stores VERY well. The World Health Organization (WHO) gives injections of 1,000,000 IU to children every six months (that equals about 5,555 IU daily) in countries with severe A deficiencies in order to prevent blindness.

This is safe because these children have NO natural source of vitamin A in their grain-based, animal-protein-deficient diets.

Historically we humans got our A from animal or fish livers, consumed infrequently but containing high amounts of vitamin A, and from vegetables containing carotinoids.

Vitamins A and D need to be balanced. The RDA for D is actually quite confusing. For example:

• No one knows how much vitamin D we need, because we don't know how much an individual might produce from light or absorb from supplements or food.

• No one knows how much vitamin D we get

• No one knows how we, as individuals, get our vitamin D, whether from light, food or supplements, and the answer would be different even within families among different family members.

• Cod liver oil was used successfully to reverse rickets, but during the same period, the late 1800s to early 1900s, irradiated (mercury vapor UV-B light) olive oil actually treated rickets better than cod liver oil and different cod liver oils had different potency -- no surprise there as standardization of supplements did not exist.

• Scientists were unable to accurately detect vitamin D in supplements or foods until about 10 to 15 years ago. Even today detecting vitamin D in foods is complex and costs $270 per item rather than the $70 cost for most other vitamins.
  

While absolutely critical to life and health, vitamin D is really a trace element in foods (and in our bodies). 1 IU (international unit) is equivalent to 0.025 micrograms and 400 IU, the current RDA, is just 10 micrograms or 0.010 milligrams. Such small amounts are difficult to detect, though they are physiologically active.

Vitamin D stores, but not in the liver and not in the same way vitamin A does. Chronic consumption of cod liver oil would build up A in the liver (and blood), as seen in these study participants, but would not build up D in the same way. For the participants to have increased values of A with increased age means chronic exposure to a vitamin A source.

If the sun and food sources do not add to one's vitamin D status, and A and D are not balanced, the condition created mimics vitamin D deficiency.

Dietary intake of vitamins A and D control expression and function of nuclear membrane receptors; for vitamin A the receptor is RXR and for vitamin D, VDR. This is a friendly cooperative competition. When dietary A is elevated in comparison to D, from whatever source, sun, foods or supplements, the condition is called a 'relative D deficiency.'

What this means in real terms is that when A is elevated, symptoms of D deficiency, including problems with bone and cartilage generation and regeneration, may occur even when serum D is normal. The reverse, too much D causing a relative vitamin A deficiency, is equally true.

The third critical player on the nuclear membrane is thyroid hormone.

The thyroid's interaction with vitamin A and vitamin D plays an important part in bone health. One would like to go back to the study participants and redo blood work testing for T3 and 25(OH)D, as well as vitamin A.

Hypo or hyperthyroidism play a significant role in osteoporosis. High doses of vitamin A can cause atrophy of the thyroid gland leading to hypothyroidism[15], which lowers T3 and thereby alters bone-remodeling, contributing to osteoporosis[16].

A second mode of action between vitamin A, vitamin D and T3 may also imbalance the nuclear membrane receptors. These receptors are genetically programmed but also respond independently to the substances, A, D and T3, they receive.

High or low levels of any of these substances actually change the number of receptors on the nuclear membrane. These receptors, as a team, are responsible for regulating cell growth and transcription. Elevation or depletion of any of the players can cause a relative deficiency or excess of one or both of the others, altering the way the cell replicates and the messages it sends to other cells.

Since most of the cell regulators are made in our bodies, and only A and D are gotten from outside, care must be taken to express moderation and balance in the intake of these substances.

Life is a balance, more so than we can begin to understand at this point in time. The rule of moderation in all things will become more and more evident as science progresses.

The interactions between these three players, vitamin A, vitamin D and thyroid, are complex and more is being discovered each year. What is clear is that all factors must be considered and balance between them respected and attempted[17].

Related Articles:

Test Values and Treatment for Vitamin D Deficiency

Breakthrough Updates You Need to Know on Vitamin D

Vitamin D Is Not A Vitamin But A Steroid Hormone Precursor

References

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14. Thompson, P. D. et al. "Vitamin D receptor displays DNA binding and transactivation as a heterodimer with the retinoid X receptor, but not with the thyroid hormone receptor." J.Cell Biochem. 75.3 (1999): 462-80.

15. Petenusci, Lopes, and Silva Netto 238-41

16. Thompson et al. 462-80

17. Dauncey et al. 6372;Frankel et al. 578-87;Rowe 275-78