Vitamin E: bone thinning link uncertain

“Vitamin E supplements intended to reduce risk of heart disease could also cause thinning of bones,” The Daily Mail reported today.

The news is based on the results of an animal study that examined one form of vitamin E, called alpha-tocopherol, and how it affected the bones of rodents. Bone continually undergoes a process of turnover, and bone mass is maintained by the balance of bone tissue being broken down and reformed. Alpha-tocopherol was found to reduce bone mass by stimulating the development of osteoclasts, a type of cell involved in bone breakdown. This meant that bone formed at a normal rate, but broke down faster. When mice and rats were fed alpha-tocopherol at levels equivalent to those found in human supplements for eight weeks, they experienced 20% bone loss. Interestingly, other forms of vitamin E did not have the same effect on bones.

This was an experimental animal study, and the effect of vitamin E on humans could be very different. Vitamin E has several functions in the body, and it’s possible that it could have some role in maintaining bone mass in humans. A large controlled study examining the effect of vitamin E on human bone is required to explore this.

People should be able to get enough vitamin E through eating a normal balanced diet, without needing to take supplements.

Where did the story come from?

This Japanese study was carried out by researchers from Tokyo Medical and Dental University, Keio University, Osaka Medical College and the University of Tokyo. It was funded by the US government’s NEXT Program, the Japan Society for the Promotion of Science, the Japanese Ministry of Education, Culture, Sports, Science and a Takeda Scientific Foundation grant. The study was published in the peer-reviewed journal Nature Medicine.

The news coverage of this story was mainly accurate. However, the findings of this animal study have been extrapolated to humans. It should not be assumed that excess vitamin E affects humans in the same way because the issue has not been specifically studied in human bone.

What kind of research was this?

This animal and laboratory study looked at a potential link between vitamin E and changes in bone density.

Although the bones appear to be solid, unchanging structures, they are actually made of living tissue and cells in the same way that muscle or skin are. Bone continuously goes through a turnover process, where bone is reabsorbed and replaced. This process allows the reshaping and replacement of bone, for example to repair any small-scale damage.

It is already known that the skeleton is affected by the fat-soluble vitamins A, D and K, but in this study the researchers investigated whether vitamin E, the other fat-soluble vitamin, also has an effect on bone. There are several different forms of vitamin E. In this study, the researchers were mainly interested in a form called alpha-tocopherol.

What did the research involve?

The researchers initially examined the bones of mice that were genetically engineered to be deficient in the alpha-tocopherol transfer protein, a protein that plays an important role in distributing vitamin E around the body. Mice were engineered in this way to investigate what happens when bones are denied alpha-tocopherol, and therefore reveal what actions the vitamin normally performs. Previous research has found that mice lacking the alpha-tocopherol transfer protein show ataxia (lack of co-ordination) and infertility.

The researchers looked at what happened when these mice were fed a normal diet and a diet supplemented with alpha-tocopherol. They then examined the effect of alpha-tocopherol on the growth and development of osteoblasts (cells involved in bone formation) and osteoclasts (cells involved in bone resorption or breakdown) grown in the laboratory.

The researchers also supplemented the diet of normal rats and mice with alpha-tocopherol at levels equivalent to those found in human supplements, and looked at the effect it had on bone growth.

What were the basic results?

The researchers found that the mice lacking the alpha-tocopherol transfer protein had high bone mass when fed a normal diet. The researchers found that these genetically engineered mice had the same rate of bone formation as normal mice, but the rate of bone resorption (or breakdown) was reduced. This bone mass abnormality was corrected when the mice were given alpha-tocopherol supplementation.

The researchers found that alpha-tocopherol promoted the development of osteoclasts, which are responsible for bone breakdown. They found that alpha-tocopherol had no effect on the growth or development of osteoblasts, which are involved in bone formation. Other forms of vitamin E, and other antioxidants, did not stimulate the development of osteoclasts.

Normal mice and rats fed alpha-tocopherol at levels equivalent to those found in human supplements for eight weeks experienced 20% bone loss. Again, this was only observed when alpha-tocopherol was added to the diet: no bone loss was seen when other antioxidants were added.

How did the researchers interpret the results?

The researchers concluded that “vitamin E stimulates bone resorption and decreases bone mass.”

Conclusion

This study examined the effect of one form of vitamin E, called alpha-tocopherol, on bone remodelling in rodents. It found that alpha-tocopherol stimulated bone breakdown and reduced bone mass through stimulating the formation of osteoclasts, a type of cell involved in bone breakdown. Interestingly, the effect of alpha-tocopherol on bone mass was independent of its antioxidant activity, and other forms of vitamin E did not have the same effect on bones.

These experiments were performed on rodents and the findings in humans could be very different. The researchers also mentioned that a number of other studies, performed on mice and humans, have found conflicting effects of vitamin E on bone. They call for a large, controlled study that examines the effect of vitamin E on human bone to see whether vitamin E decreases bone mass.

Bone undergoes turnover, and bone mass is maintained through the balance of bone formation and bone breakdown. Although this study has shown that vitamin E supplements decrease the bone mass of rodents, in humans vitamin E has several functions in the body. It is possible that it performs some role in maintaining the balance of bone turnover.

In humans, all the vitamin E that is required should be available through a balanced diet, with no need for vitamin E supplements. The amount of vitamin E required is 4mg daily for men and 3mg daily for women. If supplements are taken, the Department of Health recommends a maximum of 540mg a day.