What you should know about vitamin A and osteoporosis
Vitamin A is essential to human health in multiple ways. However, recent evidences show that needless and excessive vitamin A supplementation can affect bone health. Animal-sourced vitamin A (preformed vitamin A), and not plant-derived vitamin A (provitamin A), was shown to be associated with increased risk of osteoporotic bone fractures. But before you go cutting off vitamin A from your diet and supplements, know that low vitamin A levels have also been linked with osteoporosis. This article discusses the effect of vitamin A on bone health, how excessive intake of the vitamin A can lower bone mineral density and just how much vitamin A is too much for your bones.
by Brad Chase
Vitamin A refers to a family of related fat-soluble retinoids. These compounds can be classified into 2 groups: preformed vitamin A and provitamin A carotenoids.
Preformed vitamin A include retinol, retinal, retinoic acid and its esters. These are usually found in foods derived from animal sources such as liver, meat, fish and dairy.
Provitamin A carotenoids include beta carotene and alpha carotene. These carotenoids are responsible for the pigments of certain plants. Once consumed, the human body converts the carotene into the active forms of vitamin A.
Preformed vitamin A are also converted to retinal and retinoic acid, the active forms of vitamin A.
The body stores vitamin A in the liver in the form of retinyl esters. In the plasma, vitamin A is available as retinol and carotenoid.
The recommended daily intake values of vitamin A for children ranges from 300 micrograms to 500 micrograms. Teenagers and adults need 700 micrograms per day. However, lactating women have increased need for vitamin A (1200 – 1300 micrograms per day).
Epidemiological studies in the US showed that 26% of the dietary vitamin A intake in men comes from provitamin A carotenoids in plants. On the other hand, women usually obtain 34% of their vitamin A as carotenoids.
Besides plant and animal sources, vitamin A can also be obtained from fortified foods and dietary supplements.
Vitamin A supplementation is usually recommended to correct vitamin A deficiency. Often, doses higher than the daily recommended intake are given to quickly restore normal vitamin A levels.
However, excessive vitamin A supplementation is also dangerous. Long-term intake of excess vitamin A can cause dizziness, nausea, headache, skin disease, joint pain, bone pain, coma and death. It should be noted that only preformed vitamin A can cause these toxicity reactions.
Provitamin A carotenoids have not been linked to severe adverse presentations of vitamin A toxicity.
Multiple studies, including in vitro, animal and human studies, have confirmed that chronic intakes of excessive vitamin A can negatively affect the bone and increase the risk of osteoporosis.
The mounting evidence is further supported by the observation that northern Europe has the highest rate of osteoporosis even though its population is known for its high intake of vitamin A.
Because vitamin A supplementation is important especially for breastfeeding women and those at risk of vitamin A deficiency, it is important to establish just how much of the vitamin is too much.
The daily limit for vitamin A supplementation can be inferred from studies linking excessive intake of vitamin A to osteoporosis. Most studies found that those who took more than 1,500 micrograms per day of vitamin A (dietary and/or supplemental retinol) were most likely to have low bone mineral density and increased risk of bone fractures.
Even though the recommended upper tolerable limit for vitamin A is 2800 – 3000 micrograms/day, these studies show that 1,500 micrograms/day is the upper limit of vitamin A consumption or supplementation in order to avoid damage to the bones.
A closer examination of the evidence also reveals that just as excessive intake of vitamin A is associated with low bone mineral density, so is low vitamin A levels.
This means that to protect your bones, you should not completely avoid sources of vitamin A even though the vitamin is just as bad for the bones in excess.
But how exactly does excessive intake of vitamin A affect the bones? The exact mechanisms are unclear but the available evidence indicates that the three mechanisms discussed below contribute significantly.
When taken in excessive amounts, vitamin A may affect the balance between the formation of new bones and the breakdown of old bones.
Studies indicate that long-term intake of high amounts of vitamin A promotes the activities of osteoclasts while inhibiting the activities of osteoblasts. Osteoclasts and osteoblasts are cells responsible for bone turnover.
Osteoblasts promote the formation of new bone by releasing the protein known as osteocalcin which then binds calcium to bone matrix. This action promotes the bone mineralization and ensures the maintenance of proper bone mineral density.
Osteoclasts, on the other hand, are the cells responsible for bone resorption. They promote the breakdown of bones and the reabsorption of its minerals.
Therefore, osteoblasts are bone builders while osteoclasts are bone breakers.
By promoting bone resorption and blocking bone formation, the excessive intake of vitamin A reduces bone mineral density and makes bones weaker, more porous and more prone to fractures.
There are also indications that vitamin A in high amounts can induce cell death in osteoblasts.
Vitamin A is well known as an inducer of apoptosis (cell death or rather cell suicide). In fact, this property is exploited in the treatment of certain skin diseases with vitamin A analogs.
By inducing the death of osteoblasts, vitamin A can quickly reduce the population of this line of cells. In this way, it inhibits the formation of new bones and impairs proper bone mineralization.
Furthermore, there are indications that vitamin A may also affect osteoblasts at the gene level by blocking the genes that promote their production. Specifically, vitamin A can block the differentiation of parent stem cells into osteoblasts.
Therefore, excessive intake of vitamin A can reduce the population of osteoblasts by increasing the rate at which they die and slowing down the generation of new osteoblasts.
The end result of these inhibitions on the life cycle of osteoblasts is poor bone health.
Lastly, high intake of vitamin A has been shown to reduce the response of calcium to vitamin D.
Although bone mineralization requires calcium, the calcium absorbed from foods and supplements reaches the blood before it gets to the bones. In fact, calcium needs to be moved from the blood to the bones before it becomes useful in the treatment of osteoporosis.
One of the vitamins needed to move calcium to bones is vitamin D (vitamin K is the other vitamin).
If vitamin A reduces the response of calcium to vitamin D, it means that vitamin D cannot move calcium from the blood to the bones. Therefore, calcium supplementation will not improve bone health or reduce the risks of bone fractures.
Poor bone health is not the only negative effect of poor calcium response to vitamin D. This action of excessive vitamin A can keep calcium in the blood.
As it is transported through the body, excess blood calcium is deposited on soft tissues and organs.
The two major sites of calcium deposition are the kidneys and the walls of the arteries. At the kidneys, this can lead to the formation of kidney stones. At the arteries, it leads to the calcification of the arterial walls and increased risk of atherosclerosis and stroke.
The evidence linking excessive vitamin A intake with osteoporosis is rather solid with most studies establishing such links especially among postmenopausal women.
One example of such studies was published in the Annals of Internal Medicine in 1998.
In this study, the researchers correlated vitamin A intake with the incidence and/or risk of bone fractures in women aged 28 – 76 years. In their findings, the researchers established that vitamin A intake was linked with lower bone mineral density and increased risk of hip fracture.
Specifically, they found no association with vitamin A and the risk of osteoporosis among those who took less than 1,500 micrograms per day of the vitamin.
However, they found that those who took more than 1,500 micrograms per day of vitamin A had 10% reduction in bone mineral density (at the neck of the femur) than those who took less than 500 micrograms per day.
In their estimate, the researchers believed that every 1 mg (1000 micrograms) per day intake (above 1500 micrograms) of retinol raised the risk of hip fracture by 68%.
A 2002 study published in the Journal of Bone and Mineral Research also reached similar conclusions.
By investigating the effects of over-supplementation of vitamin A on bone health in the elderly, the researchers believed that vitamin A should be removed from the supplements given to old people because it would be easier to consume excess vitamin A from supplements than foods.
A 2002 study published in The Journal of the American Medical Association also concluded that the amount of retinol in fortified foods and supplements should be reviewed downwards.
In this study, the researchers took data from the Nurses’ Health Study involving more than 72,000 postmenopausal women.
By examining outcomes during the 18-year follow-up period of the study, they concluded that long-term consumption of foods with high retinol content can increase the risk of osteoporotic hip fractures in women.
However, they found that high intake of provitamin A carotenoid did not raise the risk of bone fractures.
Although serum retinol is measured to determine vitamin A status, experts have warned that this test is not a true indication of vitamin A levels and should not be used to recommend vitamin A supplementation.
The body keeps a store of vitamin A in the liver. Therefore, low serum retinol levels do not accurately predict vitamin A deficiency since the body soon releases some of the stored vitamin A back into the blood.
Therefore, when doctors blindly recommend vitamin A supplements after measuring low serum retinol levels, they may actually be giving excessive vitamin A and, therefore, increasing the risk of osteoporotic bone fractures.
A 2007 paper published in the journal, Nutrition Reviews, discussed these concerns. The authors recommended stable isotope dilution method for determining liver and total body vitamin A levels to accurately determine when preformed vitamin A supplementation is needed.
A 2006 study published in The American Journal of Clinical Nutrition examined the link between preformed vitamin A intake, serum levels of retinyl esters and the risk of osteoporosis.
Retinyl esters are the stable forms of retinol found in human tissues since retinol is an unstable compound.
This study found that high intakes (1500 – 2000 micrograms/day) of preformed vitamin A (retinol from animal dietary sources) did not raise the levels of serum retinyl esters. However, it did raise the ratio of retinyl esters to total vitamin A levels and also increased the risk of osteoporosis.
A 2001 study found in the Journal of Bone and Mineral Research investigated the high incidence of osteoporosis in Northern Europe despite the high intake of vitamin A by the population of the region.
The researchers conducted a double blind, crossover study involving 9 participants. They studied the effects of vitamin A (1,500 micrograms), vitamin D (2 micrograms) and a combination of the two vitamins (against placebo) on serum calcium level.
They found that supplementing with only vitamin D increased the serum levels of calcium and reduced the level of parathyroid hormone as expected. On the other hand, vitamin A alone reduced serum calcium levels.
In addition, vitamin A significantly reduced calcium response to vitamin D when both vitamins were taken.
The researchers concluded that vitamin A intake can reduce the positive effect of vitamin D on the absorption and utilization of calcium in the body.
A 2004 study published in The American Journal of Medicine provided new insights from the NHANES I (first National Health and Nutrition Examination Survey Epidemiologic) follow-up study.
By taking the data obtained from 2,799 women aged 50 – 74 years at the time of the study, the researcher correlated vitamin A intake with the incidences of hip fractures over a follow-up period of 22 years.
The results of this analysis showed that both high and low vitamin A intake was associated with increased risk of hip fractures.
This study shows that the vitamin A intake should not be completely avoided following widespread report that the vitamin is linked with increased risk of osteoporosis. Rather, the researchers showed that the relationship between vitamin A and osteoporosis followed a bell “U” curve in which the vitamin is only bad for the bones at the two extremes.
Therefore, moderate intake of vitamin A can help improve bone health and reduce the risk of osteoporosis.
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