Vitamin E may be best known for boosting skin and eye health as well as immune function. In recent years, researchers have explored the potential benefits of vitamin E on bone loss, especially in women with menopause-related osteoporosis. While data are beginning to roll in from these studies, evidence supporting a positive impact of vitamin E on osteoporosis and hip fracture risk in perimenopausal women remains elusive.
For osteoporosis, the rationale for using vitamin E is based on its antioxidant activity, which can scavenge potentially damaging free radicals. Researchers have asked whether vitamin E can help maintain the integrity of bone matrix and stimulate bone formation while minimizing bone resorption, particularly in trabecular (spongy) bone, the bone compartment preferentially affected in perimenopausal bone loss.
Vitamin E mostly consists of two isomers: alpha-tocopherol and gamma-tocopherol. Alpha-tocopherol has higher antioxidant activity and is found in nuts, seeds, vegetable oils, green leafy vegetables, fortified cereals, and vitamin E supplements. Gamma-tocopherol is known for its superior anti-inflammatory properties and accounts for about 70% of the total vitamin E intake in a typical American diet, largely sourced from soybean and other vegetable oils.
Benefits and Risks in Bone Loss Studies
Perimenopausal bone loss is caused, to a great extent, by the decrease in sex hormones. Studies of vitamin E in ovariectomized rats have yielded mixed results. This animal model lacks sex hormones and has similar bone changes to those of postmenopausal women. Some animal studies have suggested a positive effect of vitamin E on bone while others have reported no effect.
Studies in humans also have produced conflicting reports of positive, neutral, and negative associations of vitamin E with bone health. For example, the Women's Health Initiative examined the relationship between vitamin and mineral antioxidants and bone health in postmenopausal women and found no significant association between antioxidants and bone mineral density.
Another study examining data from children and adolescents enrolled in the National Health and Nutrition Examination Survey (NHANES) database found an inverse association between alpha-tocopherol and lumbar spine bone density, suggesting a deleterious effect on bone. Inverse associations also have been reported in certain studies of postmenopausal women.
High doses of alpha-tocopherol have been linked to a risk for impaired bone health through a variety of mechanisms, such as interference with vitamin K metabolism; competitive binding for alpha-tocopherol transfer protein, inhibiting the entry of beneficial vitamin E isomers, including gamma-tocopherol; and prooxidant effects that harm bone. Thus, postmenopausal women taking vitamin E supplements primarily as high doses of alpha-tocopherol might be hindering their bone health.
Data for gamma-tocopherol are more promising. Some studies hypothesize that gamma-tocopherol might uncouple bone turnover, leading to increased bone formation without affecting bone resorption. Further, a randomized controlled study of mixed tocopherols (rather than alpha-tocopherol) vs placebo reported a protective effect of this preparation on bone outcomes by suppressing bone resorption. This raises the importance of considering the specific forms of vitamin E when evaluating its role in bone health.
Limitations of Current Studies
Researchers acknowledge several limitations in studies to date. For example, there are very few randomized controlled trials assessing the impact of vitamin E on bone health. Most studies are cross-sectional or observational, even when longitudinal. Cross-sectional and observational designs prevent us from establishing a causal relationship between vitamin E and bone endpoints.
Such designs also run the risk of additional confounders that may affect associations between vitamin E and bone, or the lack thereof. These could include both known and unknown confounders. Of note, gamma-tocopherol intake data were not available for certain NHANES studies.
Further, people often consume multiple nutrients and supplements, complicating the identification of specific nutrient-disease associations. Most human studies estimate tocopherol intake by dietary questionnaires or measure serum tocopherol levels, which reflect short-term dietary intake, while bone mineral density is probably influenced by long-term dietary patterns.
Too Soon to Prescribe Vitamin E for Bone Health
Some nutrition experts advocate for vitamin E supplements containing mixed tocopherols, specifically suggesting a ratio of 50-100 IU of gamma-tocopherol per 400 IU of D-alpha-tocopherol. Additional research is essential to confirm and further clarify the role of gamma-tocopherol in bone formation and resorption. In fact, it is also important to explore the influence of other compounds in the vitamin E family on skeletal health.
Until more data are available, we would recommend following the Institute of Medicine’s guidelines for the recommended daily allowance (RDA) of vitamin E. This is age dependent, ranging from 4 to 11 mg/d between the ages of 0 and 13 years, and 15 mg/d thereafter.
Overall, evidence of vitamin E's impact on osteoporosis and hip fracture risk in perimenopausal women remains inconclusive. Although some observational and interventional studies suggest potential benefits, more interventional studies, particularly randomized controlled trials, are necessary to explore the risks and benefits of vitamin E supplementation and serum vitamin E levels on bone density and fracture risk more thoroughly.
COMMENTARY
Is Vitamin E Beneficial for Bone Health?
Sidhartha Pani, MD; Madhusmita Misra, MD, MPH
DISCLOSURES
| December 09, 2024Vitamin E may be best known for boosting skin and eye health as well as immune function. In recent years, researchers have explored the potential benefits of vitamin E on bone loss, especially in women with menopause-related osteoporosis. While data are beginning to roll in from these studies, evidence supporting a positive impact of vitamin E on osteoporosis and hip fracture risk in perimenopausal women remains elusive.
For osteoporosis, the rationale for using vitamin E is based on its antioxidant activity, which can scavenge potentially damaging free radicals. Researchers have asked whether vitamin E can help maintain the integrity of bone matrix and stimulate bone formation while minimizing bone resorption, particularly in trabecular (spongy) bone, the bone compartment preferentially affected in perimenopausal bone loss.
Vitamin E mostly consists of two isomers: alpha-tocopherol and gamma-tocopherol. Alpha-tocopherol has higher antioxidant activity and is found in nuts, seeds, vegetable oils, green leafy vegetables, fortified cereals, and vitamin E supplements. Gamma-tocopherol is known for its superior anti-inflammatory properties and accounts for about 70% of the total vitamin E intake in a typical American diet, largely sourced from soybean and other vegetable oils.
Benefits and Risks in Bone Loss Studies
Perimenopausal bone loss is caused, to a great extent, by the decrease in sex hormones. Studies of vitamin E in ovariectomized rats have yielded mixed results. This animal model lacks sex hormones and has similar bone changes to those of postmenopausal women. Some animal studies have suggested a positive effect of vitamin E on bone while others have reported no effect.
Studies in humans also have produced conflicting reports of positive, neutral, and negative associations of vitamin E with bone health. For example, the Women's Health Initiative examined the relationship between vitamin and mineral antioxidants and bone health in postmenopausal women and found no significant association between antioxidants and bone mineral density.
Another study examining data from children and adolescents enrolled in the National Health and Nutrition Examination Survey (NHANES) database found an inverse association between alpha-tocopherol and lumbar spine bone density, suggesting a deleterious effect on bone. Inverse associations also have been reported in certain studies of postmenopausal women.
High doses of alpha-tocopherol have been linked to a risk for impaired bone health through a variety of mechanisms, such as interference with vitamin K metabolism; competitive binding for alpha-tocopherol transfer protein, inhibiting the entry of beneficial vitamin E isomers, including gamma-tocopherol; and prooxidant effects that harm bone. Thus, postmenopausal women taking vitamin E supplements primarily as high doses of alpha-tocopherol might be hindering their bone health.
Data for gamma-tocopherol are more promising. Some studies hypothesize that gamma-tocopherol might uncouple bone turnover, leading to increased bone formation without affecting bone resorption. Further, a randomized controlled study of mixed tocopherols (rather than alpha-tocopherol) vs placebo reported a protective effect of this preparation on bone outcomes by suppressing bone resorption. This raises the importance of considering the specific forms of vitamin E when evaluating its role in bone health.
Limitations of Current Studies
Researchers acknowledge several limitations in studies to date. For example, there are very few randomized controlled trials assessing the impact of vitamin E on bone health. Most studies are cross-sectional or observational, even when longitudinal. Cross-sectional and observational designs prevent us from establishing a causal relationship between vitamin E and bone endpoints.
Such designs also run the risk of additional confounders that may affect associations between vitamin E and bone, or the lack thereof. These could include both known and unknown confounders. Of note, gamma-tocopherol intake data were not available for certain NHANES studies.
Further, people often consume multiple nutrients and supplements, complicating the identification of specific nutrient-disease associations. Most human studies estimate tocopherol intake by dietary questionnaires or measure serum tocopherol levels, which reflect short-term dietary intake, while bone mineral density is probably influenced by long-term dietary patterns.
Too Soon to Prescribe Vitamin E for Bone Health
Some nutrition experts advocate for vitamin E supplements containing mixed tocopherols, specifically suggesting a ratio of 50-100 IU of gamma-tocopherol per 400 IU of D-alpha-tocopherol. Additional research is essential to confirm and further clarify the role of gamma-tocopherol in bone formation and resorption. In fact, it is also important to explore the influence of other compounds in the vitamin E family on skeletal health.
Until more data are available, we would recommend following the Institute of Medicine’s guidelines for the recommended daily allowance (RDA) of vitamin E. This is age dependent, ranging from 4 to 11 mg/d between the ages of 0 and 13 years, and 15 mg/d thereafter.
Overall, evidence of vitamin E's impact on osteoporosis and hip fracture risk in perimenopausal women remains inconclusive. Although some observational and interventional studies suggest potential benefits, more interventional studies, particularly randomized controlled trials, are necessary to explore the risks and benefits of vitamin E supplementation and serum vitamin E levels on bone density and fracture risk more thoroughly.
Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.
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