We documented seasonal variations in levels of 25(OH)D and a high prevalence of vitamin D insufficiency during fall and winter in an ambulatory population of healthy western Canadians situated at 51°0
N. Although seasonal variations in serum 25(OH)D in healthy populations have been documented for several European countries and the United States,15
studies of the seasonal effects on vitamin D status in Canadians have been limited to elderly people living in institutions,16,17,18
low-income elderly people,19
and young women.20
In accord with the in vitro evidence of Webb and colleagues9
that, at a latitude of 53°N, the skin does not produce any precursors for vitamin D3
(the form generated by exposure to ultraviolet radiation) from October through March, we found that levels of 25(OH)D in late fall (virtually all measurements were obtained during November) were similar to those obtained in winter. However, we were surprised that the serum levels of 25(OH)D in the fall were significantly lower than the winter levels, given the relatively small absolute difference (4.4 nmol/L) between the 2 seasons ().
Seasonal changes in serum 25(OH)D levels may reflect synthesis of both vitamin D3
and 25(OH)D. Gascon-Barré and associates21
demonstrated an increase in expression of the gene for vitamin D3
-25 hydroxylase (CYP27A
) during spring and summer, with corresponding increases in serum 25(OH)D. These results were corroborated by Lehmann and collaborators,22
who demonstrated that both vitamin D3
and exposure to ultraviolet B radiation led to increases in expression of D3
-25 hydroxylase in keratinocytes.
This study also confirmed the importance of age as a major determinant of vitamin D status. Regardless of season, increasing age was associated with lower levels of 25(OH)D and 1,25-(OH)2
D. The cause of the age-related decline in 1,25-(OH)2
D is multifactorial. Several theories, including a decrease in renal 1α-hydroxylase activity with age,23
compounded by decreased renal function,4
and decreased availability of 25(OH)D as a substrate,24
have all been implicated in the age-related decline of 1,25-(OH)2
D. Declining levels of 25(OH)D with age have been attributed to impaired vitamin D absorption from the intestine,25
as well as a decline in the concentration of the vitamin D precursors that are normally stored in the skin.26
After adjusting for season, age and travel to lower latitudes, we found that BMI was inversely related to serum 25(OH)D. Such a relation has also been observed in postmenopausal women,27
and younger obese subjects.29
Need and associates27
suggested that the inverse relation between 25(OH)D and BMI is due a larger body pool of vitamin D and 25(OH)D or slower saturation and mobilization of these compounds from adipose tissue (or both).
Serum 25(OH)D is our best available laboratory aid for diagnosing frank vitamin D deficiency, which causes rickets in children and osteomalacia in adults. Vitamin D deficiency is typically associated with 25(OH)D levels below 25 mmol/L.30
However, identification of inadequate levels of vitamin D for optimal bone health — vitamin D “insufficiency” — is likely of greater clinical importance. The most commonly used definition of vitamin D insufficiency is the lower limit of the normal range for the 25(OH)D assay (40 mmol/L).10
However, recent investigations have suggested that the threshold for vitamin D insufficiency should be the 25(OH)D level below which parathyroid hormone secretion begins to rise. The authors of these studies have proposed that the cutoff value for vitamin D insufficiency may be as high as 80 mmol/L.31,32,33
In support of a higher threshold, it has been noted that serum 25(OH)D is lower in people who have experienced fractures than in controls.34,35
Center and colleagues36
showed that subjects with a 25(OH)D level less than 68 nmol/L had a 4-fold greater risk of major fracture over an 8-year period. In patients with osteoporosis this risk was increased 19-fold.
On the basis of the most conservative definition of insufficiency (less than 40 nmol/L), 34% of our subjects had vitamin D insufficiency at at least one point during the year (). If the proposed 80 mmol/L threshold is used, virtually all participants (97%) would be assessed as having had vitamin D insufficiency at least once during the year. Raising the threshold by only 10 mmol/L, to 50 mmol/L, nearly doubles the proportion of our study population who would be classified as having vitamin D insufficiency (to 61%).
Despite the high prevalence of vitamin D insufficiency in this population and appropriate seasonal changes, we found no relation between parathyroid hormone and serum 25(OH)D. Only a small proportion (10% to 17%) of participants had parathyroid hormone levels above the normal range of the DiaSorin assay (greater than 54 pg/mL) at any point. Similar to other studies,37,38
we observed an increase in parathyroid hormone with age, and women had higher levels of this hormone than men. In addition, parathyroid hormone increased with increasing BMI. The seasonal declines in parathyroid hormone, which lagged behind seasonal increases in 25(OH)D by one season, may be the result of previously established vitamin D stores in body fat.39
Another possible reason for the lack of an association between parathyroid hormone and 25(OH)D is that other factors, particularly calcium consumption, may have served to keep serum parathyroid hormone levels low, even during times of 25(OH)D insufficiency. Both Riggs and collaborators40
and Storm and associates41
reported wintertime suppression of parathyroid hormone with calcium supplementation (without dietary vitamin D supplementation) in postmenopausal women. In both of these studies, mean daily calcium intake was well over 1500 mg in each of the intervention groups. Storm and associates41
also reported a significant inverse relation between parathyroid hormone and 25(OH)D only when calcium consumption was less than 800 mg/day, which suggests a threshold dose of calcium for suppression of parathyroid hormone. An important limitation of our study is that we did not assess participants' dietary calcium during the study. Although the subjects had all reported relatively low calcium intake on entry into CaMOS 2 years earlier (), they probably increased their calcium intake after entering the study, as a result of their participation in an “osteoporosis study.”
This study has several other limitations that must be considered when generalizing the results to other Canadian populations. The study sample was predominately white (except for 3 individuals), which does not accurately reflect more diverse ethnic communities such as those in Vancouver and Toronto. However, given that people with greater skin pigmentation have less circulating vitamin D3
than those with lighter skin tone,42,43
it is likely that a larger proportion of dark-skinned participants would have reduced the mean serum 25(OH)D levels throughout the year. Other factors unique to the Calgary population might have led to an underestimation of the seasonal variations of 25(OH)D in the Canadian population as a whole. Calgary receives more hours of sunshine per year than any other Canadian city, particularly in the fall and winter ().44
Although sunshine hours do not accurately indicate how much time people spend in the sun, several studies have reported a direct relation between meteorologically measured sunshine hours and levels of 25(OH)D.27,31
In addition, at an elevation of 1077 m, Calgary residents are situated at a considerably higher altitude than most other Canadians (). Rigel and colleagues45
have demonstrated increases in ultraviolet B radiation of approximately 8% to 10% with every 300 m increase in elevation. Given that participants in this study lived in a region with more sunshine hours and higher elevation than most other Canadian locations, it is likely that the seasonal decreases observed in late fall and winter underestimate those of other Canadian populations. These factors also suggest that the observed prevalence of seasonal vitamin D insufficiency in a Calgary population may be a conservative estimate of vitamin D insufficiency among other Canadians.
In conclusion, we documented marked seasonal effects on vitamin D levels in a community-dwelling sample of Canadians. These results support recommendations for clinicians recently outlined by Heaney46
regarding assessment of vitamin D metabolism. According to Heaney, the reference values provided by manufacturers of 25(OH)D measurement kits should be revised. Experts suggest that optimal levels of 25(OH)D should be somewhere above 80 nmol/L (32 ng/mL).31,46
Furthermore, we do not recommend using elevated serum levels of parathyroid hormone as a surrogate marker for vitamin D insufficiency, because parathyroid hormone is modulated by several other factors, particularly calcium intake. However, despite these expert suggestions, routine measurement of 25(OH)D is probably not justified.46
Given that almost every person in our sample had serum 25(OH)D levels below 80 nmol/L at one point in the year, and that more than one-third of subjects had levels below the most conservative definition of vitamin D insufficiency, our findings support a recommendation for more aggressive vitamin D supplementation, particularly for elderly people and especially during the fall and winter months. The current dietary recommendation for vitamin D in Canada and the United States is 200 IU/day for adults (600 IU/day for those over the age of 70),47
has argued that the adult requirement should be at least 800 IU/day. Our study suggests a need to review Canada's recommendation for vitamin D nutrition.
β See related article page 1541