Zuleikaa
Fri, Aug-26-05, 06:33
I forgot about this for a while but I think it's timely.
I finally found the study I had wanted to reference but couldn't find again (isn't that always the case, lol!!)
I think this is the definitive study on vitamin D and SAD/depression. I also think it answers the toxicity issue though there was another study just on the toxicity of D3.
http://www.nutritionj.com/content/3/1/8
Research
.
Randomized comparison of the effects of the vitamin D3 adequate intake versus 100 mcg (4000 IU) per day on biochemical responses and the wellbeing of patients
Reinhold Vieth1 , Samantha Kimball1 , Amanda Hu1 and Paul G Walfish2, 3
1Department of Laboratory Medicine and Pathology, University of Toronto, Canada
2Department of Medicine, Pediatrics, and Otolaryngology, University of Toronto, Canada
3Medicine and Endocrine Oncology Program, Mount Sinai Hospital, Toronto, Canada
Nutrition Journal 2004, 3:8 doi:10.1186/1475-2891-3-8
The electronic version of this article is the complete one and can be found online at: http://www.nutritionj.com/content/3/1/8
Received 23 March 2004
Accepted 19 July 2004
Published 19 July 2004
© 2004 Vieth et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.
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Outline Abstract
Abstract
Background
Methods, Materials & Patients
Results
Discussion
Conclusions
List of abbreviations
Competing interests
Authors' contributions
Acknowledgements
References
Background
For adults, vitamin D intake of 100 mcg (4000 IU)/day is physiologic and safe. The adequate intake (AI) for older adults is 15 mcg (600 IU)/day, but there has been no report focusing on use of this dose.
Methods
We compared effects of these doses on biochemical responses and sense of wellbeing in a blinded, randomized trial. In Study 1, 64 outpatients (recruited if summer 2001 25(OH)D <61 nmol/L) were given 15 or 100 mcg/day vitamin D in December 2001. Biochemical responses were followed at subsequent visits that were part of clinical care; 37 patients completed a wellbeing questionnaire in December 2001 and February 2002. Subjects for Study 2 were recruited if their 25(OH)D was <51 nmol/L in summer 2001. 66 outpatients were given vitamin D; 51 completed a wellbeing questionnaire in both December 2002 and February 2003.
Results
In Study 1, basal summer 25-hydroxyvitamin D [25(OH)D] averaged 48 ± 9 (SD) nmol/L. Supplementation for more than 6 months produced mean 25(OH)D levels of 79 ± 30 nmol/L for the 15 mcg/day group, and 112 ± 41 nmol/L for the 100 mcg/day group. Both doses lowered plasma parathyroid hormone with no effect on plasma calcium. Between December and February, wellbeing score improved more for the 100-mcg/day group than for the lower-dosed group (1-tail Mann-Whitney p = 0.036). In Study 2, 25(OH)D averaged 39 ± 9 nmol/L, and winter wellbeing scores improved with both doses of vitamin D (two-tail p < 0.001).
Conclusion
The highest AI for vitamin D brought summertime 25(OH)D to >40 nmol/L, lowered PTH, and its use was associated with improved wellbeing. The 100 mcg/day dose produced greater responses. Since it was ethically necessary to provide a meaningful dose of vitamin D to these insufficient patients, we cannot rule out a placebo wellbeing response, particularly for those on the lower dose. This work confirms the safety and efficacy of both 15 and 100 mcg/day vitamin D3 in patients who needed additional vitamin D.
Outline Background
Abstract
Background
Methods, Materials & Patients
Results
Discussion
Conclusions
List of abbreviations
Competing interests
Authors' contributions
Acknowledgements
References
Vitamin D nutrition can affect many aspects of health because its metabolites function at many tissues. For osteoporosis prevention, the recent consensus is that 25(OH)D should exceed 72 nmol/L, and that adult consumption of vitamin D should be about 25 mcg (1000 IU)/day [1]. A recommended dietary allowance (RDA) is an intake "adequate to meet the known nutritional needs of practically all healthy persons"[2]. According to this criterion, there is still no scientific basis for an RDA for vitamin D [3,4]. Controversies and ongoing concerns about exceeding the safe upper limit (UL) for vitamin D are probably why every major brand of multivitamins marketed for older adults still contains less than the adequate intake (AI) for adults >70 y. Resistance from manufacturers may also stem from the fact that no clinical study has yet specifically used 15 mcg (600 IU)/day of vitamin D3.
Vitamin D consumption in the amount of 100 mcg (4000 IU)/day is safe and physiologic for adults [5-7]. We have characterized cross-sectional relationships between vitamin D intakes, 25(OH)D, 1,25(OH)2D and PTH in endocrine outpatients [8]. Because circulating 25(OH)D was insufficient in 25% of those patients, i.e. it was less than 40-nmol/L (<16 ng/mL), we wanted to offer them vitamin D supplements and to determine whether there are demonstrable differences between the use of the highest current AI for vitamin D, and 100 mcg (4000 IU)/day.
In addition to monitoring their biochemical responses, we enquired about participants' subjective aspects of wellbeing. Among its many potential biological effects, vitamin D nutrition may influence the brain, because brain tissue possesses the enzyme that can produce 1,25(OH)2D, the biologically active form of vitamin D [9,10]. The brain also possesses the appropriate receptors to respond to this [11-13]. Electroencephalographic readings change with season, especially in women [14]. One study has reported that vitamin D supplementation reduces depression in people with seasonal affective disorder better than does treatment with bright light [15]. One study of healthy students concluded that 10 or 20 mcg (400 or 800 IU)/day for only 5 days during winter improved mood [16]. In men with prostate cancer, 50 mcg (2000 IU)/day vitamin D improved functionality and quality of life [17]. In a large placebo-controlled, randomized study that showed that fractures are prevented with 20 mcg (800 IU)/day of vitamin D the authors also reported that self-reported health improved significantly for women, but not men [18]. In community-dwelling healthy older American men with relatively high 25(OH)D levels who were randomized to 25 mcg (1000 IU)/day vitamin D or placebo, there was no effect on health perception [19]. Likewise, in healthy American women supplemented with 10 mcg (400 IU)/day vitamin D or placebo, there was not difference in terms of perceived mood changes with season [20]. In frail elderly, a 4-month randomized study of multivitamin supplementation (5 mcg (200 IU) /day vitamin D) failed to produce an effect on wellbeing [21]. Hence, the season, dose, duration of the study, as well as the age, sex, general health of the population studied and the 25(OH)D levels before starting vitamin D can all play a role in whether an improved sense of wellbeing is seen with vitamin D supplementation.
Most patients in the northern USA presenting with diffuse musculoskeletal symptoms exhibit 25(OH)D levels less than 50 nmol/L (20 ng/mL) [22]. Women in Saudi Arabia who present with low back pain commonly have 25(OH)D levels below 50 nmol/L, and in a Phase-2 study design with no control group, they responded remarkably well to treatment with oral 25(OH)D (5000 – 10,000 IU/day) [23].
Depression scores at northern latitudes are generally worst between December and February [24], coincident with the nadir in 25(OH)D levels [25,26]. Thus, we chose these months to compare the effects of two doses of supplementary vitamin D3 on biochemical responses and measures of wellbeing of patients prescreened to be at high risk of vitamin D insufficiency during winter.
Outline Methods, Materials & Patients
Abstract
Background
Methods, Materials & Patients
Results
Discussion
Conclusions
List of abbreviations
Competing interests
Authors' contributions
Acknowledgements
References
Figures
Figure 1
Flowchart showing numbers of patients during the duration of these studies
Tables
Table 1
Statistical analysis of Study 1 scores of wellbeing (Winter 2001–2002).
Table 2
Statistical analysis of Study 2 scores of wellbeing (Winter 2002–2003).
Materials
Vitamin D3 doses were prepared in two concentrations: 700 mcg/mL and 95 mcg/mL. For this, we used crystalline cholecalciferol (vitamin D3, USP Grade, Sigma, St Louis) as previously described [27]. The crystalline vitamin D3 was dissolved in US-Pharmacopoeia-grade ethanol and calibrated based on absorbance at 265 nm using a diode-array spectrophotometer (Hewlett-Packard, Palo Alto, CA), and based on the vitamin D molar extinction coefficient of 18,300 AU/mol/L. Thus, the UV absorptivity at 264 nm was 33.4 and 5.0 AU/cm path-length respectively for the high and low dose.
Subjects (STUDY 1)
We previously reported on the biochemical characteristics of thyroid clinic outpatients [8]. The following procedures were followed in accordance with the ethical standards of Mount Sinai Hospital on human experimentation, approval was obtained from its human research ethics committee, and each participant signed an informed consent. Since current opinion is that desirable 25(OH)D concentrations should exceed 70 nmol/L [1], we offered to provide vitamin D to patients who, in spring and summer of 2001, had serum 25(OH)D <61 nmol/L, because we expected these patients to develop 25(OH)D concentrations <40 nmol/L by the next winter, based on what we knew of seasonal 25(OH)D changes in Toronto [25,28]. In late summer 2001, we sent letters to 333 of these patients. Of those who signed the consent, approved by the ethics-review committee of Mount Sinai Hospital, 46 completed at least 3 months of vitamin D supplementation (Table 1). Participants were unpaid volunteers. They were not asked about intake of dietary supplements or vitamins, because the eligibility criterion was a low 25(OH)D that demonstrated a need for supplementation. Participants and their physician were blinded as to dose, which was either 95 mcg/week (4200 IU/week; 600 IU/day) or 700 mcg/week (28,000 IU/week; 4000 IU/day). Doses were in 1 ml ethanol solution, added with a syringe to a drink and consumed once per week as we have done in previous studies [5,27]. Because vitamin doses are usually described in their daily amounts, we express the weekly doses given here in their average daily amounts of 15 mcg/day or 100 mcg/day.
Biochemical Methods
We measured intact PTH on the DPC Immulite 2000 analyzer (DPC, Los Angeles, CA). Serum 25(OH)D was measured with the DiaSorin radioimmunoassay (Stillwater, MN) with which our laboratory consistently reported close to the mean of the DEQAS international proficiency survey for this analyte [29]. Serum 1,25(OH)2D was measured with the classic, calf-thymus receptor assay, involving purification of analyte on Bond Elut C18OH cartridges (Varian, Harbor City, CA) and an internal standard to correct for losses during purification [30].
Questionnaire
To address the issue of whether the vitamin D supplementation affected sense of wellbeing, and in particular, whether consumption of 100 mcg/day offers benefits beyond those of consuming 15 mcg/day, the shipment of vitamin D was accompanied by a brief questionnaire, based on conventional depression-screening tools, and incorporating questions relating to energy and mood:
1. Has your general ENERGY LEVEL been less than average lately?
2. Has your MOOD been less than average lately?
3. Have you had problems sleeping, either too much or too little?
4. Have you lost interest or pleasure in things you normally enjoy doing?
5. Have you had a decrease in your ability to concentrate?
6. Have you lost/gained weight?
The wellbeing score for Study 1 was the total number of "YES" responses to these questions. A lower score (out of 6) reflected "better" wellbeing.
For those patients willing to continue taking the vitamin D, the dose originally assigned was continued through the winter 2002–2003, thereby overlapping their vitamin D supplementation with the patients in Study 2, and completing the same questionnaires as the patients in Study 2. Of the original 93 subjects who initially consented, 46 patients continued taking vitamin D3 through to November 2002.
STUDY 2
At the end of summer, 2002, more patients of the outpatient endocrinology clinic were selected, this time based on 25(OH)D levels that had been measured as <51 nmol/L, and who had not participated previously. At the beginning of November 2002, invitation letters were mailed to 324 patients along with a consent form, and a new questionnaire. Of these, 14 were returned as changed mailing addresses, 243 did not respond. We received 67 returned, signed consents with completed questionnaires within the allotted time period (approximately 2 wks from mailing) (Figure 1).
Upon receipt of the completed consent, each patient was randomized as before. Ten questions were added to the questionnaire, based upon the seasonal health questionnaire of Thompson and Cowan [31]:
7. Has your GENERAL HEALTH been less than average lately?
8. Have you felt less rested upon waking from sleep lately?
9. Have you experienced a down feeling or inappropriate guilt?
10. Have you felt less socially active lately?
11. Have you been indecisive lately?
12. Have you felt less productive or less creative lately?
13. Has your appetite increased or decreased?
14. Have you experienced any cravings for carbohydrates (bread, pasta, rice, sugary foods), more than normal?
15. Has it been more difficult to deal with daily stress?
16. Have you felt irritable or anxious lately?
The wellbeing score for Study 2 was the total number of "YES" responses to these questions, with a lower score (out of 16) reflecting "better" wellbeing. This was mailed at recruitment and in February 2003.
Statistical analysis
Statistical analysis and graphical presentation were carried out using SPSS version 11 (SPSS, Inc., Chicago, IL). As recommended by Jones et al, analyses pertaining to wellbeing were done and presented using both the intent-to-treat approach (all available data), as well as per-protocol, using only data for patients completing both December and February questionnaires [32]. For each of these, statistical analyses were done using both parametric, t-test comparisons, and equivalent non-parametric approaches, as specified in the following results section. For the wellbeing score of Table 2, the null hypothesis had been one tailed, i.e. that the higher dose would improve scores compared to the lower dose. Thus, although all p-values are presented here as 2-tailed, a one-tail null hypothesis was disproved if the 2-tail p < 0.1 for differences in the direction expected a-priori. Statistical analyses of longitudinal biochemical data are presented here as parametric assessments, using ANOVA. If ANOVA indicated that significant differences existed for the biochemistries, we performed 2-tail paired-t-tests because these were comparisons defined a priori, and not post-hoc comparisons. i.e. Since 25(OH)D levels had been expected to be higher after months of supplementing with vitamin D, the unexpected observation would have been to see no difference (i.e. beta error), the risk of which would have been increased with Bonferroni or Dunnett comparisons. Mean values are given with ±SD values. Correlation of wellbeing vs months on dose was done with Spearman's rank-order correlation coefficient, which measures association at the ordinal level.
Outline Results
Abstract
Background
Methods, Materials & Patients
Results
Discussion
Conclusions
List of abbreviations
Competing interests
Authors' contributions
Acknowledgements
References
Figures
Figure 2
Biochemical responses to vitamin D3 supplementation of endocrine outpatients during one year
Figure 3
Cross-sectional presentation of the effect of duration of vitamin D supplementation on quartiles of well-being scores obtained during winter 2002–2003
Study 1. Biochemical responses
Results of biochemical tests are presented in Figure 2. For those patients in whom biochemistry data were tested within 2–6 months after starting vitamin D, both doses increased 25(OH)D significantly, with higher levels in the higher vitamin D dose group than in the lower dose group. In both groups, statistically significant suppression of PTH was detected only after 6 months of supplementation. While mean PTH was slightly lower for the 100 mcg/day group, PTH was not significantly different between dose groups. There were no significant differences in serum total or plasma ionized calcium concentrations, either over time, or between groups. There were no significant differences or changes in 1,25(OH)2D concentrations between groups, or over time. Information relevant to determining nutrient intake requirements for adults is indicated by the bottom whiskers for 25(OH)D concentration measured beyond 6 months: 15 mcg (600 IU)/day resulted in average 25(OH)D concentrations of 79 (±30 SD) nmol/L with a minimum non-outlier value of 44 nmol/L; 100 mcg (4000 IU)/day resulted in average 25(OH)D concentrations of 112 (±41 SD) nmol/L with a minimum non-outlier value of 69 nmol/L (note that during winter, 25(OH)D levels should be lower than the summer/fall values presented for data >6 mo beyond the start of treatment).
Compared to the high-dose group, the median increase in 25(OH)D per mcg vitamin D intake was significantly larger in the lower dose group (p = 0.011, using the Mann-Whitney test; p = 0.003, using the t-test). For the lower dose group, the median 25(OH)D increase per mcg of vitamin D dose was 2.2 nmol/L/mcg/d, (25th and 75th percentile values were 0.6, 4.1 nmol/L/mcg/day respectively). For the higher dose group, the median 25(OH)D increase was 0.6 nmol/L/mcg/day (25th and 75th percentile values were 0.4, 0.9 nmol/L/mcg/day respectively).
Study 1 Effects on wellbeing (winter 2001–2002)
Table 1 summarizes the scores for wellbeing, based on six questions. For the patients enrolled in Study 1, mean 25(OH)D concentrations prior to December 2001 were 49 (±9 SD) nmol/L for the higher dose group, and 46 (±9 SD) nmol/L for the lower dose group (Figure 2). Based on the conventional two-tail analysis, none of the comparisons between doses or between December and February was statistically significant. However, the hypothesis at the outset of this research was the one-tailed question of whether the higher dose of vitamin D has a better effect on wellbeing than the lower dose. Therefore, we conclude from Study 1, with 95% confidence (based on 2-tail p < 0.1), that 100 mcg (4000 IU)/day of vitamin D did result in a significantly greater improvement in wellbeing, compared to the effect of 15 (600 IU)/day. This statistical conclusion was the same whether the analysis was based on the intention-to-treat analysis (analyses on the left side of Table 1) or per protocol analysis (analyses on the right side of Table 1), and the statistical conclusion was the same with either parametric or nonparametric statistical analysis.
Study 2 Effect on wellbeing (winter 2002–2003)
Table 2 summarizes the results for wellbeing, based on 16 questions. For each dose group of Study 2, 25(OH)D mean concentration prior to December 2002 was 39 (±9 SD) nmol/L. Wellbeing improved from December to February for all new patients enrolled in the study (p < 0.001); wellbeing also improved during this time for the lower-dose patients remaining on the protocol from the previous year (p = 0.012). There was no statistically significant change for the group that had been consuming 100 mcg (4000 IU)/day since the previous year. However, those consuming the higher dose for one year were already statistically at a lower (better) score for wellbeing at the beginning of December 2002 compared to the corresponding Study-1 lower-dose group (2-tail t-test, p = 0.039). We also compared the groups based on the subset of six questions used in Study 1; this produced the same statistical differences shown in Table 2 for all 16 questions. That is, in Study 2, and using the 6 questions that were the basis of wellbeing in Study 1, both doses lowered the total score, but this time, there was no difference in effect between 15 mcg (600 IU)/day versus 100 mcg (4000 IU)/day.
As a form of meta-analysis, to combine the wellbeing data of both Study cohorts in these experiments, we have summarized the data from Table 2 as box-plots in Figure 3. This figure highlights interactions between the duration of vitamin D supplementation, and wellbeing. After Month 0, the quartile values show that the response was greater (lower score) with the higher dose than with the AI dose of vitamin D. For the pooled data in the figure, the nonparametric correlation of wellbeing vs months on vitamin D indicated a significant decline (improvement in wellbeing) for participants consuming 100 mcg (4000 IU)/day (p = 0.002). However, for those consuming 15 mcg (600 IU)/day the correlation with time on the dose was not statistically significant.
Outline Discussion
Abstract
Background
Methods, Materials & Patients
Results
Discussion
Conclusions
List of abbreviations
Competing interests
Authors' contributions
Acknowledgements
References
Since these were endocrine outpatients, we had expected their general perception of wellbeing to be less than that of the general population. Since older persons with 25(OH)D <50 nmol/L risk losing muscle strength [33] and development of musculoskeletal pain [22,23], there was reason to consider non-osteoporosis-related responses to vitamin D in patients with such low 25(OH)D levels. From an ethical perspective, patients who are selected because of low 25(OH)D levels should receive at least a meaningful amount of vitamin D [34,35]. We provided at least the vitamin D AI for the oldest age group, 15 mcg (600 IU)/day, because some of our patients were older than 70 years, and because age does not affect the 25(OH)D response to a dose of vitamin D [8,36].
The greatest biochemical responses to the vitamin D occurred after six months of supplementation. During follow-up, there was no clear plateau in 25(OH)D (Figure 2). Lack of a plateau may reflect season, because the final samples for 25(OH)D in the figure were taken through the summer and autumn, when 25(OH)D levels should be higher than in winter. Differences between the first and the third box of each cluster in Figure 2 reflect the effects of the intervention, not the season, because these samples had been collected about one year apart. Future studies of vitamin D supplementation should take into account that it may take a year to reach stable 25(OH)D levels. Although previous work (including our own) has implied that plateau levels of 25(OH)D can occur within five months [5,37], the impression of a plateau reflects the time pattern of sampling; i.e. samples taken at short time intervals can give a false impression of a plateau.
Higher levels of 25(OH)D generally correlate with lower concentrations of PTH [1,8]. The present data confirm that both doses produced a significant suppression of PTH. The box-plots in Figure 2 suggest a somewhat greater PTH suppression with the higher dose of vitamin D, and we attribute the lack of a statistical difference in PTH between the dose groups to the relatively small sample sizes in this study. In our cross-sectional study of 1741 such patients we observed steady decreases in PTH as 25(OH)D increased [8]. There was no evidence of a change in plasma ionized calcium as a result of this relatively long-term use of vitamin D at a relatively high dose of 100 mcg (4000 IU)/day. We should point out that this dose is not high in the physiologic context, because it approximates what healthy men acquire daily, if they work outdoors [7]. The present data extend the time-frame for follow-up beyond what has been reported previously, and our focus was on patients who did require additional vitamin D; this contrasts with earlier studies of 100 mcg (4000 IU)/day that involved healthy volunteers, where most were already sufficient in vitamin D [5,7].
Lansdowne and Provost reported that 10 or 20 mcg (400 or 800 IU)/day of vitamin D, given for 5 days improved the mood of healthy Australian students during winter [16]. Their protocol provided a total of 100 mcg (4000 IU) vitamin D or less, which could not have produced a detectable change in 25(OH)D concentrations. The results we obtained in Study 1 indicated that the 100 mcg (4000 IU)/day dose of vitamin D resulted in fewer affirmative responses to questions that were mainly related to depression. However, since statistical significance was one-tailed – which we did regard as valid because the effect was in the direction hypothesized beforehand – we wanted to confirm the greater efficacy of the higher dose. The next winter, the protocol was refined (Study 2) to include a more stringent recruitment, requiring lower summer 25(OH)D concentrations (<51 nmol/L) and additional questions relating to wellbeing [31].
In Study 2, both dose groups exhibited highly statistically significant improvement in wellbeing between December 2002 and February 2003. The only patients who did not improve during the second winter were those who had been maintained on the higher dose of vitamin D for the 12 months leading up to December 2002, and whose wellbeing score had already improved during Study 1. Overall, both studies presented here were consistent with the expectation that higher vitamin D nutrition improves sense of wellbeing. The relatively greater improvement during Study 2 compared to Study 1 could be explained to the lower initial 25(OH)D concentrations of Study 2. The eventual wellbeing response of low-dose patients from Study 1 may reflect a cumulative effect of their vitamin D intake. Since there was no placebo group used in this study, we cannot rule out other reasons for improvement. Questionnaire portions of this research were carried out entirely through the mail, with randomized blinded doses, and minimal direct contact between personnel and the participants; thus, it is not likely that investigator bias played a role. The winter was more severe during Study 2, so we doubt that weather would have explained the improved wellbeing reported during Study 2.
In retrospect, the SF-36 questionnaire, which is acceptable to the FDA as a measure of health outcome, would have been better to assess wellbeing [38]. Nonetheless, simple screening tools like ours do correlate with, and perform about as well as more complex, well-validated questionnaires [39]. Therefore, it as unlikely that a different questionnaire would have affected the sorts of changes we observed, or the conclusions about wellbeing in relation to vitamin D.
Outline Conclusions
Abstract
Background
Methods, Materials & Patients
Results
Discussion
Conclusions
List of abbreviations
Competing interests
Authors' contributions
Acknowledgements
References
The present studies are the first to demonstrate, specifically, the efficacy of the highest current AI for vitamin D. They also demonstrate, in adults older than studied previously, the safety of longer-term vitamin D supplementation with 100 mcg/day. This work suffered from the ethical constraint that participants should not receive a placebo supplement. While this weakens the quality of evidence about wellbeing, we considered it important to report the findings, because they provide keys to the better design of subsequent research into effects of vitamin D on wellbeing. Patients known to have low 25(OH)D levels should not be deprived of vitamin D, and by providing these patients with the AI dose of vitamin D there seems to have been moderate improvement in wellbeing, albeit less of a response than with 100 mcg/day. To demonstrate the largest absolute effects of vitamin D on wellbeing, investigators would be advised to focus on a population with low initial 25(OH)D concentration <50 nmol/L. However, the relative question of whether a higher dose of vitamin D has a greater effect on wellbeing compared to the AI requires firstly, a larger sample size than was available for either of the present studies, and secondly, a focus on adults prescreened not to have the low initial 25(OH)D concentrations that we had specified in Study 2.
This work provides a new perspective about the safety of vitamin D. In the conventional sense, neither dose of vitamin D affected serum calcium levels. However, safety is also supported by the fact that reported wellbeing of patients was not made worse by the consumption of the higher dose (instead, it improved). If wellbeing had deteriorated in any way, this would have been accepted readily as a reason to keep vitamin D intake recommendations low. Although our work confirms the anti-depressant, wellbeing effects reported with short-term intervention and smaller doses of vitamin D [15-17], we found that with the higher dose, these effects were sustained for the longer term of one year – which seems unlikely to happen if this were simply a placebo effect. Effects on wellbeing or depressive symptoms should be important criteria for targeting an RDA for vitamin D, and these still require further study.
List of abbreviations
25-hydroxy-vitamin D or calcidiol, 25(OH)D; 1,25-dihydroxy-vitamin D or calcitriol, 1,25(OH)2D; adequate intake, AI; micrograms, mcg (the Greek letter mu, μ, is not used in this document because some software replaces it with "m", causing a 1000-fold error in the dose); recommended dietary allowance, RDA.
Competing interests
None declared.
Authors' contributions
RV and PW conceived this study. PW was responsible for the clinical care of the patients. AH and SK prepared vitamin D, prepared mailings, helped in designing the study, and maintained the data. SK and RV performed statistical analyses and were responsible for writing the publication.
Acknowledgements
Financial Support. This work was supported by the Canadian Institutes for Health Research (RV), and by the Mount Sinai Hospital Foundation and Department of Medicine Research Fund (PGW) as well as support from the Temmy Latner Dynacare and Julius Kuhl Family Foundations (PGW).
Outline References
Abstract
Background
Methods, Materials & Patients
Results
Discussion
Conclusions
List of abbreviations
Competing interests
Authors' contributions
Acknowledgements
References
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Zuleikaa
Fri, Jan-13-06, 08:39
This is a two page handout that I've put together on vitamin D. I've copied it into a one-page double-sided handout. I've given out over 100 copies so far.
Feel free to duplicate and hand it out too.
Vitamin D Facts
If it hurts to press firmly on your sternum, you may be suffering from chronic vitamin D deficiency right now.
Adequate vitamin D levels achieved through exposure to sun, consumption of oily fish, and supplements can prevent 80% of D deficiency related diseases and cancers.
30 times more cancer deaths are attributed to lack of vitamin D from lack of sun exposure than skin cancer deaths from too much sun exposure.
Always take calcium and magnesium with vitamin D supplements. Vitamin D will pull calcium from the bones if adequate calcium is not ingested. Magnesium assists in calcium uptake.
Per day: 1,000-12,000 IU vitamin D3, 1800 mg calcium, and 1200 mg magnesium. Required vitamin D dose depends on season, resident latitude, skin tone, weight, age, and presence of D deficiency symptoms.
Vitamin D, D3, is not really a vitamin; rather it is a powerful steroid and a super hormone that tells your body how to work. It controls hormones and cellular growth; it helps to absorb calcium for strong bones and teeth; it ensures muscle strength and balance; and it protects against immune diseases, prenatal physical and neurological disorders, birth defects, diabetes, inflammation, depression, and cancers. Vitamin D deficiency has been implicated in over 70 illnesses and diseases and has been proven to prevent or remit 28 kinds of cancers, most especially breast, ovarian, prostate, .
You may have heard that vitamin D is toxic in high levels and no one should take more than 800-2,000 IUs per day. That is not true and is just perpetuation of old, outdated information relating to man-made vitamin D.
• Natural vitamin D, cholecalciferol, is named D3; manmade vitamin D, ergocalciferol, is named D2.
• Natural vitamin D, D3, has been tested at 20,000 IUs per day over a 5 year period and found non toxic.
• No incident of natural vitamin D toxicity has resulted in death.
• Cases of proven natural vitamin D toxicity have been the result of industrial accidents or accidental mega doses in excess of 1 Million IUs per day over a prolonged period.
• Hypercalcemia (high amounts of calcium in the blood) has been pointed to as an indication of vitamin D toxicity; however, hypercalcemia is also, and more often, a symptom of vitamin D deficiency.
• Vitamin D supplements are safe for all ages including infants.
--A 2 year old was given 4 Million IUs of vitamin D over a 5 day period resulting in vitamin D toxicity. His symptoms were diarrhea, stomach ache, and hypercalcemia. He was treated for the hypercalcemia over a period of 3 months and fully recovered with no negative results.
--Prior to 1985 all infants and children in Norway and Sweden were given 2,000-4,000 IUs a day of D3. Those countries then had the lowest rates of juvenile diabetes, and developmental, and childhood illness of industrialized nations. These children, now adults, have the lowest rates of cancer compared to those who were not supplemented.
--27 sickly children ages ranging from 2-12 were given 9,000 IUs a day of vitamin D3 for six weeks one winter; they stopped getting sick.
• Vitamin D toxicity arises at a blood level of >250 ng/ml.
• Vitamin D levels can be easily tested with a 25(OH)D test.
--Ignore the lab ranges for normal on this test as the norms were established using a D deficient population.
--Any reading below 60 ng/ml is deficient.
--Any reading of 75-125 ng/ml is optimal.
--Individuals in the tropics naturally have vitamin D levels ranging from the mid 100s-200 ng/ml.
• It’s impossible to get adequate amounts of vitamin D from diet alone. Sunlight exposure is the only reliable way to generate vitamin D in your own body. When adequate sunlight is not available to produce vitamin D, supplements must be taken.
• Chronic vitamin D deficiency cannot be reversed overnight: it takes months of high dose vitamin D supplementation and sunlight exposure to rebuild the body's bones and nervous system.
• Suggested vitamin D use by the body has been put at 4,000 IUs per day.
• Proven vitamin D use by the body has been shown at 7,000 IUs per day.
• The best time to produce vitamin D from sun exposure during the day is between the hours of 10-2, the time most people are indoors, and the very hours that people are advised to avoid the sun.
• Use of sunscreen/block of even SPF=8 cuts 95% of vitamin D production.
• Vitamin D cannot be produced by sun shining through glass.
• The further you live from the equator, the longer exposure you need to the sun in order to generate vitamin D. Canada, the UK and most U.S. states are far from the equator.
• People with dark skin pigmentation need 20 - 30 times as much exposure to sunlight as fair-skinned people to generate the same amount of vitamin D.
• The ability to make vitamin D decreases with age.
• There is no possible vitamin D production from the sun during winter for those living above 41 degrees latitude north or south of the equator.
• Daily vitamin D needs cannot be met from the sun during winter 37 degrees from the equator.
• Clouds, aerosols and thick ozone events reduce the duration of vitamin D synthesis considerably, and can suppress vitamin D synthesis completely even at the equator.
• Rates of vitamin D deficiency diseases: high blood pressure, Alzheimer’s, MS, autoimmune, Crohn’s heart, Hodgkin’s, and Parkinson’s diseases, schizophrenia, mental illness, alcoholism, fibromyalgia, lupus, rheumatoid arthritis, diabetes type I & II, and cancers rise with distance from the equator.
• Having kidney disease or liver damage can impair your body's ability to activate circulating vitamin D.
• Blacks have higher rates of D related illnesses: high blood pressure, diabetes, hyperthyroid, hyper parathyroid, cancers—especially prostate, breast, colon, and ovarian cancers, obesity, and bone pain.
• Sufficient levels of vitamin D are crucial for calcium absorption. Without sufficient vitamin D, the body cannot absorb calcium, rendering calcium supplements useless.
Vitamin D_Obesity Link
Vitamin D is stored in fat. Vitamin D controls insulin…insulin causes hunger/cravings and stores fat…fat captures vitamin D and makes it not available for the body to use…
Resulting in less vitamin D which means less insulin control …higher insulin causes more hunger/cravings and stores more fat…fat captures vitamin D and makes it not available for the body to use…and on and on.
Obesity and the vitamin D deficiency--related condition osteomalacia often go hand in hand. Osteomalacia is characterized by extreme bone and muscle pain and weakness. When an obese person has osteomalacia, the bone and muscle pain and weakness make it virtually impossible to participate in any sort of physical activity that might help the individual manage his or her weight. As a result, the individual becomes even more obese, which will in turn worsen his or her vitamin D status and exacerbate the osteomalacia.
Further, for these people initial weight gain leads to more clothes covering the body, and less time spent outdoors in the sun due to practical and esteem-related reasons. When the obese are outside, less skin is exposed to the sun for vitamin D production which leads to vitamin D deficiency which starts and continues the above cycles.
Recent research has shown that being vitamin D deficient interferes with the secretion of a hormone called leptin, which signals the brain when a person has consumed enough fat. Building the vitamin D in that person's bloodstream to normal levels will restore that process.
Obese individuals, depending on weight, require 2-4 times the vitamin D supplementation of normal weight individuals because some amount of vitamin D is captured in fat and is, therefore, not bio-available.