Vitamin D Concentrations, Health Conditions, and Mortality
Vitamin D Concentrations, Health Conditions, and Mortality
This large epidemiological study of community-dwelling men aged 70 to 97 living in Australia confirms that low vitamin D levels are associated with a range of poor health outcomes, poor physical and functional outcomes, and mortality. Controversy remains about optimal serum 25(OH)D levels for human health in older age. The Endocrine Society Clinical Practice Guidelines recommend levels of 25(OH)D of 75.0 nmol/L or greater for optimal benefits for health. A recent review concluded that "the risk of disease is lower if serum 25(OH)D exceeds 75 nmol/L than if the level is at 53 nmol/L." Contrary to these recommendations, the current study found no additional health benefits of serum 25(OH)D levels of 75.0 nmol/L or greater. The findings suggest that the optimum range for 25(OH)D in older men is between 50.0 and 74.9 nmol/L for a wide range of health conditions, physical performance measures, disability, falls, and death.
Recent data suggest that low serum 25(OH)D concentrations may play a role in the pathogenesis of many chronic diseases. The current study is the first to examine associations between 25(OH)D levels and a wide range of health conditions, assessments of general health, physical and cognitive function, and mortality in older men living in the community in one study. The findings also show that low 25(OH)D levels were associated with poor self-reported health and multiple comorbidities and that low 25(OH)D levels were associated with self-reported diabetes mellitus and hyperglycemia. This is in line with evidence from a recent review that suggested that 25(OH)D alters muscle metabolism, specifically its sensitivity to insulin, which is related to insulin resistance and type 2 diabetes mellitus, and these findings have also been shown in a recent meta-analysis.
As expected, low 25(OH)D levels (<50.0 nmol/L) were associated with poor grip strength, an indicator of muscle strength; 25(OH)D has direct effects on muscle modulated by specific vitamin D receptors present in human muscle tissue. There is also evidence that locally produced 1,25-dihydroxyvitamin D may directly activate the vitamin D receptor, which is found in many different cell types throughout the body and has a physiological role in a number of organs. Studies on the associations between grip strength and 25(OH)D status have been contradictory. A meta-analysis of trials in older people with 25(OH)D levels of less than 25.0 nmol/L showed that vitamin D supplementation improved proximal muscle strength. Somewhat surprisingly, the current study also found that grip strength and balance were optimal in the range of 25(OH) D from 50.0 to 74.9 nmol/L. This is in contrast to the Invecchiare in Chianti study, which showed that men with serum 25(OH)D levels of 75.0 nmol/L or greater had significantly higher handgrip strength than those with serum 25OHD levels of less than 75.0 nmol/L. Another more-recent study in older Italian men found that grip strength was greater with greater 25(OH) D levels up to 100 nmol/L. This population group included a healthy group of older men who had higher mean vitamin D levels than men in the current study, which was thought to be due to the large amount of time spent outdoors gardening, which may have contributed to high 25(OH)D levels.
Low 25(OH)D concentrations (<50.0 nmol/L) were associated with all-cause mortality in the current study, even with adjustment for confounding variables and potential mediators of mortality. This is consistent with other epidemiological studies in older community-dwelling adults and with a meta-analysis of randomized controlled trials of vitamin D supplements in older adults. Some studies have found high 25(OH)D levels to be associated with lower mortality. A recent study in adults aged 50 to 74 and a review suggest that optimal 25(OH)D concentrations for mortality endpoints begin at 75.0 nmol/L.
In contrast, the current study did not show any difference in mortality risk with 25(OH)D levels of 50.0 to 74.9 nmol/L and levels of 75.0 nmol/L and greater. This is consistent with findings from the Third National Health and Nutrition Examination Survey, which also found that participants in the lowest quartile of 25(OH)D (<44.5 nmol/L) had a higher risk of all-cause mortality than those in the other three quartiles. Perhaps surprisingly, a few studies have found high 25(OH)D levels to be associated with greater mortality. The Uppsala Longitudinal Study of Adult Men, in a cohort of men living in the community, showed that high and low concentrations of 25(OH)D were associated with higher risks of all-cause and cancer-specific mortality.
The current study shows that only 6.6% of men were taking vitamin D supplements, despite the high prevalence of low 25(OH)D levels (<50.0 nmol/L). It was surprising to find that users and nonusers of vitamin D supplements had comparable 25(OH)D levels. These findings are clinically important because they suggest that there may be problems with adherence or prescription of appropriate doses of vitamin D supplements for older men.
The main strengths of the study are that it involved a large, representative sample of community-dwelling Australian men aged 70 and older. The age distribution of the men in CHAMP is similar to that of the target population and the prevalence of self-reported disease in CHAMP participants is similar to that found in a recent Australian national telephone survey of men's health. It was also possible to use prospective data to investigate whether low 25(OH)D concentrations were associated with all-cause mortality and falls.
There are some limitations to the study. Dietary vitamin D intake was not measured, nor was data obtained on time spent outdoors or sunscreen use, which is important because exposure to ultraviolet (UV) B light is the primary source of 25(OH)D. The falls data were obtained by recall every 4 months and may have been subject to underreporting. Most of the findings came from cross-sectional data, and these associations cannot establish a cause-and-effect relationship and may be due to reverse causality (poor health limiting outdoor activity, leading to inadequate sun exposure and low 25(OH)D levels). It was reassuring to find the expected upward trend in prevalence of skin cancer with higher 25(OH)D levels, consistent with greater risk of skin cancer with greater UV exposure. Another limitation is that measurement of parathyroid hormone (PTH), which might have strengthened the study, was not included in the analysis. There is evidence that lower 25(OH)D and higher PTH levels are associated with greater risk of loss of muscle mass and poor muscle strength (sarcopenia) and greater risk of mortality in community-dwelling older people.
In conclusion, this study suggests that maintaining 25(OH)D levels between 50.0 and 75.0 nmol/L is important for a range of health conditions, functional indicators, and mortality in older community-dwelling men. Contrary to some recent recommendations, serum 25(OH)D levels of 75.0 nmol/L or greater were not found to have additional benefits in terms of a broad range of health outcomes.
Discussion
This large epidemiological study of community-dwelling men aged 70 to 97 living in Australia confirms that low vitamin D levels are associated with a range of poor health outcomes, poor physical and functional outcomes, and mortality. Controversy remains about optimal serum 25(OH)D levels for human health in older age. The Endocrine Society Clinical Practice Guidelines recommend levels of 25(OH)D of 75.0 nmol/L or greater for optimal benefits for health. A recent review concluded that "the risk of disease is lower if serum 25(OH)D exceeds 75 nmol/L than if the level is at 53 nmol/L." Contrary to these recommendations, the current study found no additional health benefits of serum 25(OH)D levels of 75.0 nmol/L or greater. The findings suggest that the optimum range for 25(OH)D in older men is between 50.0 and 74.9 nmol/L for a wide range of health conditions, physical performance measures, disability, falls, and death.
Recent data suggest that low serum 25(OH)D concentrations may play a role in the pathogenesis of many chronic diseases. The current study is the first to examine associations between 25(OH)D levels and a wide range of health conditions, assessments of general health, physical and cognitive function, and mortality in older men living in the community in one study. The findings also show that low 25(OH)D levels were associated with poor self-reported health and multiple comorbidities and that low 25(OH)D levels were associated with self-reported diabetes mellitus and hyperglycemia. This is in line with evidence from a recent review that suggested that 25(OH)D alters muscle metabolism, specifically its sensitivity to insulin, which is related to insulin resistance and type 2 diabetes mellitus, and these findings have also been shown in a recent meta-analysis.
As expected, low 25(OH)D levels (<50.0 nmol/L) were associated with poor grip strength, an indicator of muscle strength; 25(OH)D has direct effects on muscle modulated by specific vitamin D receptors present in human muscle tissue. There is also evidence that locally produced 1,25-dihydroxyvitamin D may directly activate the vitamin D receptor, which is found in many different cell types throughout the body and has a physiological role in a number of organs. Studies on the associations between grip strength and 25(OH)D status have been contradictory. A meta-analysis of trials in older people with 25(OH)D levels of less than 25.0 nmol/L showed that vitamin D supplementation improved proximal muscle strength. Somewhat surprisingly, the current study also found that grip strength and balance were optimal in the range of 25(OH) D from 50.0 to 74.9 nmol/L. This is in contrast to the Invecchiare in Chianti study, which showed that men with serum 25(OH)D levels of 75.0 nmol/L or greater had significantly higher handgrip strength than those with serum 25OHD levels of less than 75.0 nmol/L. Another more-recent study in older Italian men found that grip strength was greater with greater 25(OH) D levels up to 100 nmol/L. This population group included a healthy group of older men who had higher mean vitamin D levels than men in the current study, which was thought to be due to the large amount of time spent outdoors gardening, which may have contributed to high 25(OH)D levels.
Low 25(OH)D concentrations (<50.0 nmol/L) were associated with all-cause mortality in the current study, even with adjustment for confounding variables and potential mediators of mortality. This is consistent with other epidemiological studies in older community-dwelling adults and with a meta-analysis of randomized controlled trials of vitamin D supplements in older adults. Some studies have found high 25(OH)D levels to be associated with lower mortality. A recent study in adults aged 50 to 74 and a review suggest that optimal 25(OH)D concentrations for mortality endpoints begin at 75.0 nmol/L.
In contrast, the current study did not show any difference in mortality risk with 25(OH)D levels of 50.0 to 74.9 nmol/L and levels of 75.0 nmol/L and greater. This is consistent with findings from the Third National Health and Nutrition Examination Survey, which also found that participants in the lowest quartile of 25(OH)D (<44.5 nmol/L) had a higher risk of all-cause mortality than those in the other three quartiles. Perhaps surprisingly, a few studies have found high 25(OH)D levels to be associated with greater mortality. The Uppsala Longitudinal Study of Adult Men, in a cohort of men living in the community, showed that high and low concentrations of 25(OH)D were associated with higher risks of all-cause and cancer-specific mortality.
The current study shows that only 6.6% of men were taking vitamin D supplements, despite the high prevalence of low 25(OH)D levels (<50.0 nmol/L). It was surprising to find that users and nonusers of vitamin D supplements had comparable 25(OH)D levels. These findings are clinically important because they suggest that there may be problems with adherence or prescription of appropriate doses of vitamin D supplements for older men.
The main strengths of the study are that it involved a large, representative sample of community-dwelling Australian men aged 70 and older. The age distribution of the men in CHAMP is similar to that of the target population and the prevalence of self-reported disease in CHAMP participants is similar to that found in a recent Australian national telephone survey of men's health. It was also possible to use prospective data to investigate whether low 25(OH)D concentrations were associated with all-cause mortality and falls.
There are some limitations to the study. Dietary vitamin D intake was not measured, nor was data obtained on time spent outdoors or sunscreen use, which is important because exposure to ultraviolet (UV) B light is the primary source of 25(OH)D. The falls data were obtained by recall every 4 months and may have been subject to underreporting. Most of the findings came from cross-sectional data, and these associations cannot establish a cause-and-effect relationship and may be due to reverse causality (poor health limiting outdoor activity, leading to inadequate sun exposure and low 25(OH)D levels). It was reassuring to find the expected upward trend in prevalence of skin cancer with higher 25(OH)D levels, consistent with greater risk of skin cancer with greater UV exposure. Another limitation is that measurement of parathyroid hormone (PTH), which might have strengthened the study, was not included in the analysis. There is evidence that lower 25(OH)D and higher PTH levels are associated with greater risk of loss of muscle mass and poor muscle strength (sarcopenia) and greater risk of mortality in community-dwelling older people.
In conclusion, this study suggests that maintaining 25(OH)D levels between 50.0 and 75.0 nmol/L is important for a range of health conditions, functional indicators, and mortality in older community-dwelling men. Contrary to some recent recommendations, serum 25(OH)D levels of 75.0 nmol/L or greater were not found to have additional benefits in terms of a broad range of health outcomes.
Source...