REVERSE THE POST-WW2 GLOBAL SHIFT FROM HEALTHY ANABOLIC OUTDOOR (VIT D AND ANDROGEN ie DIET CHOLESTEROL– FAT DOMINANCE) EXERCISE ABUNDANCE TO THE RECENT LETHAL CARBOHYDRATE-SUGAR- ESTROGENICS- CORTISOL INDOOR TV DOMINANCE AND FAMINE.
NEW STUDIES:
More Canadian and USA studies confirm that vigorous vitamin D need applies especially to those living in far northern USA-Canada and EurAsia etc; but also to all of us globally who spend little time well exposed to the sun- especially the more driven who both live/work indoors and cover even our limbs and heads outdoors as eg more ‘observant’ adults of many faiths do. As a new Creighton Univ study shows, we are at minimal risk of kidney stones on vigorous supplement vit D3 provided we balance it with enough water and magnesium supplement,
This is why in this age of increasing stress, longevity, epidemics, and pollution of both environment and the food and medicine chains, we have for a couple of years now been advocating and taking vitamin D3 – on a century of voluminous evidence (62500 papers on Pubmed alone) since 1914 from top nutritional scientists like Drs Jack Drummond, Linus Pauling, Walter Stumpf, Chris Nordin, Chris Gallagher, Rob Heaney, John Cannell, Bill Grant, Mike Holick, Cedric Garland, ea – at least vit D3 50 000iu a week (~7000iu/d) ie a million units every 20 weeks; retail costing R30 ie R6pm for us aging frailer types (half that dose ie 50 000iu twice a month @R3/month for the poor/ well or small kids).. at R12/US$, that costs all of $3 to $6 a year.
On about 9000iu vit D3 average supplement/day, my total 25OH vit D bloodlevel runs about 90-100 ng/ml ie 220-250 nmol/l. so only 400- 1000iu vit D /day will boost the vit D bloodlevel and benefits little if not trivially.
But vigorous D3 dose must be buffered by vit K2 about >100mcg/day , magnesium about 400mg/d, and the usual basket of other ~50 vits, minerals and other natural supplements, to protect us from kidney and arterial calcification etc. We have previously highlighted trials eg from Pakistan showing that even 600 000iu vit D3 a month ie ~20 000iu/day safely and greatly improves recovery and healing from severe PTB+- AIDS in eg frail Pakistatin patients; whereas overdose of 90year old patients with a 2million iu vit D3 dose (in Netherlands) produced no toxicity. Hence we load sick patients with (an antibiotic-like ) 200 000 to 400 000iu dose before continuing weekly or fortnightly maintenance- with the sickest fattest getting the highest dose, and infants scaled down accordingly (after a loading dose of eg 25 000iu) to eg 1000-2000iu/d, or 50000iu 1/2 scoop ie 25000iu every 2 weeks- the older extrapolation (as for adults) of ~100iu/kg/day.
For the concerned vegan, vitamin D is vegetarian: supplement of vit D2 is extracted from yeast or mushrooms; vit D3 by UV irradiation of cholesterol from lanolin. Like all life, since vitamin D soltriol is a sun-induced sterol oil product (in this case of cholesterol which in turn is built via vitamin C ascorbic acid from plant glucose-sugar), vitamin D does not contain or be made from animal flesh ie animal protein nitrogen any more than does fish oil.
Vitamin D may keep low-grade cancer from becoming aggressive:
http://www.sciencedaily.com/releases/2015/03/150322080155.htm Taking vitamin D supplements could slow or even reverse the progression of less aggressive, or low-grade, prostate tumors without the need for surgery or radiation, scientists say. Taking vigorous vits C & D does this for all cancers, all disease.
VITAMIN D DEFICIENCY IS ASSOCIATED WITH INSULIN RESISTANCE INDEPENDENT OF INTRACELLULAR CALCIUM, DIETARY CALCIUM AND SERUM LEVELS OF PARATHORMONE, CALCITRIOL AND CALCIUM IN PREMENOPAUSAL WOMEN. Da Silva Ferreira T, Sanjuliani AF ea . Nutr Hosp. 2015 Apr 1;31(n04):1491-1498.
25-Hydroxyvitamin D in the range of 20 to 100 ng/mL doesnt increase kidney stones. Am J Public Health. 2014 Sep;104(9):1783-7 Garland, Heaney ea Creighton Univ, USA Increasing 25-hydroxyvitamin D serum levels can prevent a wide range of diseases. There is a concern about increasing kidney stone risk with vitamin D supplementation. The study included 2012 participants followed prospectively for a median of 19 months. Thirteen individuals self-reported kidney stones during the study period. Multivariate logistic regression was applied to assess the association between vitamin D status and kidney stones.We found no statistically significant association between serum 25-hydroxyvitamin D and kidney stones (P = .42). Body mass index was significantly associated with kidney stone risk (odds ratio = 3.5; 95% confidence interval = 1.1, 11.3). We concluded that a serum 25-hydroxyvitamin D level of 20 to 100 nanograms per milliliter has no significant association with kidney stone incidence.
A Statistical Error in the Estimation of the Recommended Dietary Allowance for Vitamin D. Letter to Veugelers, P.J. and Ekwaru, J.P., Nutrients. 2015 Mar 10;7(3):1688-90. doi: 10.3390/nu7031688. Nutrients 2014, 6, 4472-4475; doi:10.3390/nu6104472. Heaney , Garland ea. 1Creighton University & University of California, San Diego, GrassrootsHealth, Encinitas, CA . Recently Veugelers and Ekwaru published data indicating that, in its dietary reference intakes for calcium and vitamin D, the Institute of Medicine (IOM) had made a serious calculation underestimation [2]. Using the same data set as had the IOM panel, these investigators showed that the Recommended Dietary Allowance (RDA) for vitamin D had been underestimated by an order of magnitude. Veugelers and Ekwaru, using the IOM’s data, calculated an RDA of 8895 IU per day. They noted that there was some uncertainty in that estimate, inasmuch as this value required an extrapolation from the available data, which did not include individuals receiving daily vitamin D inputs above 2400 IU/day.[…].
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4210929/ Nutrients. 2014 Oct; 6(10): 4472–4475.Statistical Error in the Estimation of Recommended Dietary Allowance for VitaminD Paul J. Veugelers* and John Paul Ekwaru University of Alberta, Canada
The Institute of Medicine (IOM) issues dietary recommendations on the request of the U.S. and Canadian governments. One of these recommendations is the Recommended Dietary Allowance (RDA). The RDA is the nutrient intake considered to be sufficient to meet the requirements of 97.5% of healthy individuals [1]. The RDA for vitamin D is 600 IU per day for individuals 1 to 70 years of age and is assumed to achieve serum 25-hydroxyvitamin D (25(OH)D) levels of 50 nmol/L or more in 97.5% of healthy individuals [1]. Serum 25(OH)D is the established proxy for vitamin D status and levels of 50 nmol/L or more have been shown to benefit bone health and to prevent disease and injury [1].
The IOM based their RDA for vitamin D on an aggregation of 10 supplementation studies that were carried out during winter months and at locations with latitudes above the 50th parallel north to minimize the influence of cutaneous vitamin D synthesis [2,3,4,5,6,7,8,9,10,11]. As several of these 10 studies examined more than one supplementation dose, collectively they provided 32 study averages of serum 25(OH)D levels. These are replicated as the green diamonds in Figure 1. The IOM regressed the 32 study averages against vitamin D intake to yield the dose response relationship of vitamin D intake and serum 25(OH)D (green solid line in Figure 1). The IOM further calculated the lower and upper 95% confidence prediction interval based on the 32 study averages and the standard deviation of these 32 study averages (green dashed lines in Figure 1). On the basis of this, the IOM estimated that 600 IU of vitamin D would achieve an average 25(OH)D level of 63 nmol/L and a lower 95% confidence prediction limit (2.5 percentile) of 56 nmol/L. The latter value was rounded downwards to 50 nmol/L to accommodate uncertainty in the estimation [1]. This data point (600 IU vitamin D, 50 nmol/L) is the basis for the current RDA and for the IOM’s conclusion that an intake of 600 IU of vitamin D per day will achieve serum 25(OH)D levels of 50 nmol/L or more in 97.5% of individuals.
The correct interpretation of the lower prediction limit is that 97.5% of study averages are predicted to have values exceeding this limit. This is essentially different from the IOM’s conclusion that 97.5% of individuals will have values exceeding the lower prediction limit. To illustrate the difference between the former and latter interpretation, we estimated how much vitamin D is needed to achieve that 97.5% of individuals achieve serum 25(OH)D values of 50 nmol/L or more. For this purpose we reviewed each of the 10 studies used by the IOM. Eight studies reported both the average and standard deviation [2,5,6,7,8,9,10,11]. These eight studies had examined a total of 23 supplementation doses [2,5,6,7,8,9,10,11]. For each of these 23 study averages we calculated the 2.5th percentile by subtracting 2 standard deviations from the average (depicted by yellow dots in Figure 2). Next, we regressed these 23 values against vitamin D intake to yield the lower prediction limit (red line in Figure 2). This regression line revealed that 600 IU of vitamin D per day achieves that 97.5% of individuals will have serum 25(OH)D values above 26.8 nmol/L rather than above 50 nmol/L which is currently assumed. It also estimated that 8895 IU of vitamin D per day may be needed to accomplish that 97.5% of individuals achieve serum 25(OH)D values of 50 nmol/L or more. As this dose is far beyond the range of studied doses, caution is warranted when interpreting this estimate. Regardless, the very high estimate illustrates that the dose is well in excess of the current RDA of 600 IU per day and the tolerable upper intake of 4000 IU per day [1].
The public health and clinical implications of the miscalculated RDA for vitamin D are serious. With the current recommendation of 600 IU, bone health objectives and disease and injury prevention targets will not be met. This became apparent in two studies conducted in Canada where, because of the Northern latitude, cutaneous vitamin D synthesis is limited and where diets contribute an estimated 232 IU of vitamin D per day [12]. One study estimated that despite Vitamin D supplementation with 400 IU or more (including dietary intake that is a total intake of 632 IU or more) 10% of participants had values of less than 50 nmol/L [13]. The second study reported serum 25(OH)D levels of less than 50 nmol/L for 15% of participants who reported supplementation with vitamin D [14]. If the RDA had been adequate, these percentages should not have exceeded 2.5%. Herewith these studies show that the current public health target is not being met. We recommend that the RDA for vitamin D be reconsidered to allow for appropriate public health and clinical decision-making.
update 1 March 2015: Screening for Vitamin D Deficiency: Is the Goal Disease Prevention or Full Nutrient Repletion?
Since its founding, the USPSTF has sought to provide a firm evidential base for early detection strategies, evaluating such screening methods as mammography and prostate-specific antigen testing. Although it has also evaluated a few interventions, its predominant focus has been testing for markers that identify persons at risk who are likely to benefit from preventive action. Only recently has the USPSTF ventured into the field—or perhaps the minefield—of nutrition, a territory distant from screening tests and risk assessment, with different and unfamiliar landmarks.
The USPSTF presents its conclusions on testing for vitamin D deficiency (1), reporting that it was unable to find evidence for or against such testing. It noted that one of the likely reasons was the absence of a scientific consensus on both the level of vitamin D status that should be judged “deficient” and what the measurable manifestations of deficiency might be. These are also issues for many other nutrients, such as folate, ascorbate, calcium, and protein. Vitamin D may have seemed to offer a way out of this confusion because serum 25-hydroxyvitamin D [25-(OH)D] concentration is generally recognized as one of the best indices of status for any of a broad array of nutrients. Also, it is now readily measurable and widely utilized.
One of the reasons its promise has not been realized is that most studies of vitamin D efficacy have used a disease-avoidance model, which is the standard approach used by the Institute of Medicine (IOM) for most nutrients (2). Furthermore, disease prevention is the explicit focus of the USPSTF. Nevertheless, the IOM and USPSTF approaches effectively equate health with the absence of disease, an equivalence that nutritionists have long rejected. Instead, nutritionists focus on full nutrient repletion when possible. The inevitable gap between disease prevention and nutrient repletion is still largely unexplored territory. For many nutrients, it can be surprisingly wide, as suggested in this case by studies of the intake required to provide vitamin D in human breast milk in quantities sufficient to meet the needs of infants (3). The IOM’s adult requirement for vitamin D is 600 IU/d (4), which is judged to be sufficient to protect against osteoporotic fracture. In contrast, quantitative and empirical evidence indicates that vitamin D intake from breastfeeding needs to be approximately 6000 IU/d (3, 5). Although high compared with the adult recommendation, such an intake almost exactly reproduces the measured vitamin D status of contemporary Africans leading ancestral lifestyles (6). Such populations provide perhaps our best window on vitamin D levels prevailing during the millennia over which human physiology was adapted to its environment by natural selection.
Whatever the actual requirement or 25-(OH)D cutoff may be, there is another likely reason that the evidence is unclear. The USPSTF drew from systematic reviews and meta-analyses of studies of vitamin D effects, such as the one accompanying the current report (7). In general, the criteria for including studies in such reviews are methodological rather than biological. Of the 6 published biological criteria (8) for including published reports in meta-analyses, the review published in this issue met only 2 (comparable basal status and same chemical form), and several of its component studies met none. Including studies that could never have been informative in the first place (especially when they are large) inevitably biases any review toward the null.
What seems not to have been widely appreciated is that vitamin D exhibits flat response regions at both low and high values of vitamin D status, with a sharp rise in the approximate center of the physiologic range of 25-(OH)D values (8). Studies like the WHI (Women’s Health Initiative), which enrolled women with low vitamin D status values and used a vitamin D dose insufficient to move them into the response range, provide little useful information about vitamin D efficacy. Yet, precisely such studies were included in the review by LeBlanc and colleagues (7). This is not to criticize the WHI, which was designed more than 20 years ago (before vitamin D pharmacology was well-understood), but it is to criticize contemporary reviews and meta-analyses that fail to take advantage of newer information or to use critical biological criteria (8) for selection of studies for analysis of biological effects.
In addition, a disease-avoidance approach becomes problematic for micronutrients in general (and vitamin D in particular) when one understands that micronutrients do not actually cause any of the effects simplistically attributed to them. Although necessary for cell response, such micronutrients by themselves do not initiate or cause the response concerned. For example, vitamin D is a component of the biochemical apparatus that opens the genome to allow access to DNA information needed for a particular cell or tissue response. In terms of cell function, this dependence means that when supplies of the micronutrient are inadequate, cellular response is blunted. This is dysfunction, but not clinically manifest disease. Such dysfunction may indeed lead ultimately to various diseases, but disease prevention remains a dull tool for discerning the defect, and a disease-prevention approach clearly does not measure whether the organism has enough of the nutrient to enable appropriate physiologic responses, such as lactation.
Finally, and aside from the USPSTF’s findings, one must ask whether treating without first testing is sound practice. Certainly, it would be rational to do so if the condition being treated is prevalent and the treatment is safe and inexpensive. That is the case with another micronutrient, iodine, and the iodination of salt. However, the current situation is different because consuming sufficient iodine generally does not require conscious adherence to a particular regimen, whereas taking vitamin D does. Usually, testing improves patient adherence because it provides patient-specific, personally applicable information. General assurances that one probably needs extra vitamin D are not as compelling a motivator as knowing one’s number. Thus, whether the practitioner adheres to the widely divergent guidelines of the IOM (4), the Endocrine Society (9), or the American Geriatrics Society (10), measuring vitamin D status seems to be warranted, not so much to diagnose deficiency but to determine patient status relative to the selected guideline.
update 20 Jan 2015 a new USA study Ng et al. Vitamin D status and survival of metastatic colorectal cancer patients: at the 2015 Gastrointestinal Cancers Symposium found that patients with metastatic colorectal cancer with higher vitamin D levels survived a third longer than those with lower levels – 32.6 months compared to 24.5.
update 12 Jan 2015 As the poet Juvenal (died 130AD) wrote: Mens sana in sano corporis– a healthy mind in a healthy body. Its great how the prime antistress homeostatic hormones- a pinch of natural melatonin at night, with ENOUGH daytime anabolic soltriol calciferol vitamin D3, restores good sleep, orchestrate homeostasis of all other hormones especially of the crucial adrenals and gonadals and thus thyroid hormones. ..
Sleep. 2015 Jan 12. Massa ea, Harvard. Low Vitamin D and Poor Sleep in Older Community – Dwelling Men : vitamin D3 is important for sleep duration and quality. 16% of this study population had very low levels of vitamin D (< 20ng/mL 25(OH)D). Lower serum vitamin D levels linked with short (< 5 h) sleep duration,doubled the odds ratio [OR] 2.15 for the highest (≥ 40ng/mL) versus lowest (< 20 ng/mL) quartile of 25(OH)D,; Ptrend = 0.004) and lowering sleep efficiency. And low vitamin D is a major associate of major depression – Józefowicz ea Univ Lodz, Poland 2014..
Thanks to global human (mostly male) greed enslaving the masses the past 7 millennia ie since at least Sumerian times, we have moved rapidly in our lifetime post WW2 from global homeostatic (food, commodities) plenty to a world of dyshomeostasis- cacostasis stress chaos – in most countries from Afghanistan to Zimbabwe. Just a few years ago South Africa led Africa in productivity and skills, and still has the biggest reserves of riches- minerals- in the world; with boundless natural power (sun, sea) and manpower to drive industry and food production. But in 20 years post apartheid, the ruling ANC under Mbeki and the Zumas has with selfserving treasonous greed brought South Africa to its knees with cacostasis, destruction of continuous water, electricity ; school education, organized and quality food provision ie agriculture, social security, the post office, the national airline, health services, Home Affairs and pensions). Now there are rapidly increasing functionally illiterate or old 16 million on state grants supported by the 6 million capable of meaningfully working and paying taxes if they dont emigrate. And state grants have now been extended to age 23yrs because state school leavers are practically unskilled for anything but being labourers. .
The national powergrid and oil reserves have been degraded so that total indefinite blackouts are now imminent, never mind weekly “outages” crippling work- the economy – and destroying appliances. Never mind increasingly pandemic influenza and HIV, antibiotic resistance puts us in the post-antibiotic era in this age of deadly resistant TB and STDs, with reckless immoral leaders like Zuma and Vavi leading the mob in extramarital sex and provoked violence. .
So as never before, everyone from conception to grave needs realistic regular vitamin D3 supplement at about R3 a month to bolster mental and physical health of children, mothers and the working , never mind the ailing aging, to reduce illhealth costs. . Stress- through raised thyroid, sympathetic and cortisol levels and depressed gastrointestinal, cardiovascular, musculoskeletal and immune control, grossly disrupts homeostasis and shifts victims into catabolic estrogen-dominance , insulin resistance mode- which only the hormone supplements D3 and melatonin, and the essential vitamins and minerals if not risk-laden androgenics can try to balance,
George Chrousos ea. University Athens, Greece since Nat Rev Endocrinol. 2009 and now Neuroimmunomodulation. 2015 write: Stress – glucocorticoids – and disorders of the stress system- cacostasis vs homeostasis. All organisms must maintain complex dynamic equilibrium- homeostasis- which is constantly challenged by internal or external adverse forces – stressors. Stress occurs when homeostasis is threatened or perceived; homeostasis is re-established by various physiological and behavioral adaptive responses. Neuroendocrine hormones have major roles in the regulation of both basal homeostasis and responses to threats, and are involved in the pathogenesis of diseases characterized by cacostasis – dyshomeostasis. The stress response is mediated by the stress system, partly located in the central nervous system and partly in peripheral organs. The central, greatly interconnected effectors of this system include the hypothalamic -pituitary-adrenal (HPA) axis and hormones arginine vasopressin, corticotropin-releasing hormone and autonomic norepinephrine centers in the brainstem. Optimal basal activity and responsiveness of the stress system is essential for a sense of well-being, successful performance of tasks, and appropriate social interactions. By contrast, excessive or inadequate basal activity and responsiveness of this system might impair development, growth and body composition, and lead to a host of behavioral and somatic pathological conditions.. Glucocorticoids, the end-products of the HPA axis, play a fundamental role in the maintenance of both resting and stress-related homeostasis and, undoubtedly, influence the physiologic adaptive reaction of the organism against stressors. If the stress response is dysregulated in terms of magnitude and/or duration, homeostasis is turned into cacostasis with adverse effects on many vital physiologic functions, such as growth, development, metabolism, circulation, reproduction, immune response, cognition and behavior. A strong and/or long-lasting stressor may precipitate and/or cause many acute and chronic diseases. Moreover, stressors during pre-natal, post-natal or pubertal life may have a critical impact on our expressed genome.
VITAMIN D ECONOMY & GOAL OF SCREENING: Heaney and Armas, Creighton University QUANTIFYING THE VITAMIN D ECONOMY: Nutrition Reviews Dec 2014; and Screening for Vitamin D Deficiency: Is the Goal Disease Prevention or Full Nutrient Repletion? Ann Intern Med. Nov 2014 write: sunlight and food contribute only modestly to the relevant optimal total serum vit D and 25OHvit D levels: unsupplemented individuals who average blood 25OHvit D of 20 ng/mL are receiving about 2,000 IU/day from nonsupplement sources (i.e food and sun) – whites double the amount compared to dark blacks from skin. . It has been established for 30 years that in fair-skinned individuals, a single exposure to UV-B at one whole-body minimum erythema dose can produce a rise in serum 25D that is equivalent to an oral dose of D3 in the range of 10,000 to 25,000 IU, ie by as little as 10–15 min of whole-body exposure at mid-day in mid-summer in a pale-skinned individual. Pale-skinned northern Europeans show a rise in serum 25D of 9 ng/mL (23 nmol/L) at the end of 4 weeks of exposure. By contrast, in dark-skinned individuals, the rise was half ie 4.5 ng/mL . Meat eaters exhibit higher human 25D status . Input gaps left after estimating solar inputs (on the order of 1,300–1,600 IU/day, as noted above) could well be filled by hitherto unrecognized food sources. For example, Taylor et al.21 report a combined (D3 plus 25D) content of 112 IU vitamin D equivalents for 200 g of beef tenderloin or an egg, associated with 2 ng/mL greater level of serum 25D. The Grassroots Health project collects data on supplement type and has found no difference in the 25D concentration achieved with either 5,000 or 10,000 IU daily doses, irrespective of whether the D3 was delivered via a gel cap in oil or as dry powder in a tablet (unpublished data; S. McDonnell, personal communication). vitamin D could be absorbed from orange juice. On the other hand, fat malabsorption syndromes are known to lead to vitamin D deficiency, and the mechanism is generally considered to be a specific impairment in the absorption of fat-soluble vitamin D. However, poor absorption may reflect not so much mucosal dysfunction, as simple sweeping of any fat-soluble compound out of the gut, dissolved in the unabsorbed fat. Dawson-Hughes et al.,35 using pharmacokinetic methods in individuals with normal absorptive function, reported equal absorbability for D3 under fasting and high-fat meal conditions, with slightly better absorption from a low-fat meal. Mulligan and Licata,36 in an observational study of 17 poor responders to oral D preparations, reported greater absorption from a large meal containing fat than from intake on an empty stomach. However, the limited data, taken as a whole, suggest that the effects of dosage form or vehicle are probably small.
Finally, the issue of D2 versus D3 needs brief mention. Formerly considered controversial, there now seems to be a growing consensus37 that, for equimolar quantities, orally administered D3 raises serum 25D by about twice as much as D2.38–42 This has been shown for bolus doses, short-term continuous administration (12 weeks), and long-term continuous administration (12 months).
Intestinal absorption of D3 is mainly from the jejunum and ileum. Absorbed vitamin D can be found in both the portal venous blood and the lymph that drains the small intestine. The lymphatic pathway may have particular physiological significance for orally acquired vitamin D, since it avoids a first pass of the absorbed vitamin D through the liver. This suggests that the quantitative relationship between vitamin D and 25D will be the same regardless of whether vitamin D enters from the skin or the gut.
Diffusion from the skin into the blood is slow, with a half-time of about 3 days.7 This half-time means that when regular sun exposure is the principal source of D3, serum D3 concentration will be essentially constant.
it is reasonably certain that the concentration of vitamin D in fat tissue is substantially higher than the concentration in serum. – a given volume of fat tissue contains approximately 12 times as much vitamin D as the same volume of serum. However, a several-fold gradient is not surprising as D3 solubility in fat is effectively limitless, while DBP capacity, which is large, is finite.
Assuming a diffusional mechanism and a total body fat mass of 35% of body weight, total body stores in an individual weighing 70 kg would range from 900 to 2,800 µg (37,000 to 113,700 IU). Using the calculations set forth in the prior section and applying them to an individual with a serum 25D level of 20 ng/mL, whose metabolic consumption would be ∼2,000 IU vitamin D/day, the total amount in the reservoir would provide enough of a reserve for 18–57 days at that same rate of utilization. At a serum 25D level of 40 ng/mL, that same reserve would support consumption for only 9–28 days. Neither estimate comes close to compensating for the “vitamin D winter” of most temperate latitudes. The smallness of this reserve explains why even outdoor summer workers who had high daytime skin exposure experienced reductions in 25D averaging approximately 20 ng/mL (50 nmol/L) by late winter. Of note, their 25D values had reached >50 ng/mL (125 nmol/L) by late summer, which is roughly the same as that reported for East Africans living ancestral lifestyles.48 This study indicates both that existing stores at the end of summer were not adequate to maintain the achieved summer level and that the late winter level (∼30 ng/mL) represented a utilization of approximately 3,000 IU/day.
Chemical partition
Extracellular 25(OH)D The first step in the chemical conversion of D3 is 25-hydroxylation.Bikle et al.51 showed that skin cells contain all the requisite enzymatic apparatus to produce both 25D and 1,25D. However, it is doubtful that under ordinary circumstances, skin is a major source of the extracellular 25D measured in serum (D. Bikle, personal communication). Other sources remain to be identified.
The efficiency with which D3 is converted to 25D varies widely from individual to individual. Various reasons can be put forth for these inter-individual differences that, though studied in somewhat less detail, have been reported by many investigators. One example is the variable methylation of the CYP2R1 gene and, hence, variable expression of the hepatic 25-hydroxylase.53 While there is currently no final answer, it is clear that differences in intestinal absorption of D3 could not explain the slow rise in participant B, relative to participant A. Moreover, the internal consistency in the shape of the respective curves virtually excludes methodological variability as a cause of the difference.
Extracellular 1,25(OH)2D The second hydroxylation, which produces extracellular 1,25D, occurs predominantly in the proximal convoluted tubular cells of the kidney. While 25-hydroxylation is not highly regulated, the opposite is true for 1,25D, the synthesis of which is upregulated by parathyroid hormone and low serum inorganic phosphorus concentration and downregulated by fibroblast growth factor-23. Note that 1,25D is a principal regulator of intestinal absorption of calcium; during this process, it acts by upregulating expression of the calcium transport apparatus of the enterocyte. This is an endocrine effect as it is mediated through serum endocrine-like activity and exhibits a typical negative feedback control loop. Under usual conditions, 1,25D is necessary for regulation of calcium absorption. However, it is not the only factor involved in this process. It should also be noted that in the absence of other vitamin D metabolites, 1,25D by itself has been reported not to be sufficient to elevate intestinal calcium absorption.55,56
As would be expected for regulator molecules, the serum half-time of 1,25D is short (hours). Its concentration in serum is a reflection mainly of relative calcium need—being high in individuals on low-calcium diets or in those with calcium malabsorption and low in individuals with high calcium intakes. Also, 1,25D has long been recognized to be calcemic when used therapeutically. The mechanism is generally attributed to intestinal calcium absorption, but this cannot be a satisfactory explanation, as increased metabolic input alone (i.e., without considering output) is rarely sufficient to elevate the serum concentration of any metabolite. Moreover, 1,25D and its analogs do not elevate calcium absorption in patients with end-stage renal disease,57 a condition in which the calcemic effect of 1,25D is often readily apparent. While not adequately explored, there remains another possibility, i.e., an effect of 1,25D on bone-lining cells, where a fall in bone fluid pH to just below 7.0 is enough to solubilize bone mineral sufficiently to elevate serum calcium.58
Physical partition
The distinction between the endocrine and the autocrine pathways is one aspect of the physical partition between extracellular and intracellular processing of the vitamin. The prevailing assumption seems to be that most or all of the D3 entering the body is 25-hydroxylated and that the resulting 25D circulates in the blood, where it serves as the substrate for both renal and extrarenal 1 -α-hydroxylation, with the renal 1,25D product circulating in the blood like 25D and with the extrarenal 1,25D never being expressed in the only accessible body compartment, i.e., the blood.
As Hollis and Wagner59 have pointed out, D3 enters cells more readily than does 25D and, as noted above, there are several enzymes other than the hepatic CYP2R1 that are capable of 25-hydroxylation of D3.49,50 Hence, a physical partition of the vitamin D pathways prior to the 25-hydroxylation step has to be given serious consideration. That this is more than just a theoretical possibility is suggested by the fact, noted earlier, that oral 25D elevates serum 25D to a substantially greater extent than does oral D3.28–30 This was shown first by Barger-Lux et al.28 in a 10-week dosing study involving the two molecules. Figure 9 plots the 25D response to the two agents observed in a group of 54 healthy adults and shows a clear divergence of the dose response curves, with a greater than seven-fold difference in slopes. Cashman et al.,30 using a different design, found an approximate five-fold difference in response after 10 weeks of dosing, and Bischoff-Ferrari et al.,29 an approximate four-fold difference after 17 weeks of dosing.
Figure 9
Change in serum 25D plotted as a function of intake for varying oral doses of 25D and D3. Data from Barger-Lux et al.28
That there should be a greater rise in 25D when oral 25D is the source is, in a sense, trivial, as oral 25D is immediately reflected in the serum, while oral vitamin D must first be 25-hydroxylated, a process that, as described above, is necessarily slower, sometimes substantially so. Only a proper pharmacokinetic study that compares area-under-the-curve values for the two agents can fully quantify this difference. Such a study must either be long enough to allow the 25D plateau to be reached while on continuous dosing of D343 or, if using a bolus dose design, must follow the time course for the two agents for probably 4 months so as to allow full 25-hydroxylation of the administered D3 and full consumption of the administered 25D. No such data are currently available, and this aspect of the physical partition must remain speculative. Nevertheless, the issue is an important one, not just for the therapeutics of 25D but also for a full understanding of the vitamin D economy (see below).
The 25D half-time (as measured by Clements et al.60–62 using tracer-labeled 25D) presents certain puzzling features in its own right. A half-time of, say, 20 days (toward the lower end of the range found by Clements et al.) translates to a daily turnover of about 3.47% of the total mass of extracellular 25D. If the size of daily utilization is known, it is possible to calculate the size of the 25D mass from that fractional utilization rate. If all of the vitamin D input to the body is converted to extracellular 25D, then at a serum 25D concentration of 20 ng/mL (requiring, as shown above, a daily input of ∼50 µg), that 50-µg input is numerically equal to the daily turnover. So, total 25D mass would be 50/0.0347, or close to 1,500 µg. This figure is larger by an order of magnitude than that of the measurable total serum content of 25D, and the discrepancy becomes even larger at higher serum 25D concentrations or longer half-times. This seeming discrepancy has not been noted previously, with one potential reason being the computational difficulty of harmonizing biological units (IU), first with mass concentrations (µg/mL), then with SI units (nmol). However, if a substantial fraction of daily input of D3 is 25-hydroxylated intracellularly, after which it is immediately activated to 1,25D, then only the 25D in the extracellular compartment would be labeled by a tracer-based approach to kinetic analysis, and the calculated daily utilization of the circulating 25D would be lower and the corresponding 25D mass estimate would be closer to what is known from blood and soft tissue content. These calculations provide support for the suggestion of Hollis and Wagner59 that “parent compound D” has more functional significance than has usually been thought.
There is one quantitative aspect of the physical partition, whether occurring prior to or after the 25-hydroxylation step, which seems inescapable. Whether one takes as optimal a serum 25D concentration of 20 ng/mL or 40 ng/mL, the molar equivalent D3 inputs required to sustain either level are far higher than the moles of 1,25D required to support the calcium economy. As noted above, a serum 25D of 40 ng/mL requires approximately 4,000 IU/day, or 100 µg/day, and a serum 25D of 20 ng/mL requires approximately 2,000 IU/day, or 50 µg/day. By contrast, the calcium economy requires between 0.5 µg and 2.0 µg of 1,25D/day. (Higher doses, as noted above, produce hypercalcemia.) It follows that >90% of D3 utilization is occurring along the intracellular/autocrine pathway. If that is not the case, then most of the D3 input to the body is degraded metabolically and not used at all. The latter possibility seems quite improbable, particularly in view of the marginal or subadequate vitamin D status that seems nearly universal. Answering this question of the relative potency of oral D3 and 25D will illuminate the partition of D3 between the extracellular and intracellular pathways and will be an important step in unraveling the puzzle of the physical partition.
One instance in which the pre-25D intracellular pathway is operative is the transfer of vitamin D activity into human breast milk.59,63 25D does not transfer across the secretory mucosa of the mammary gland with sufficient efficiency to produce enough vitamin D activity in milk to nourish the infant, while D3 does. However, for this to occur, D3 must be present in the blood that bathes the mammary secretory apparatus. In earlier work, Hollis et al.63 showed that the concentration of vitamin D in human milk was about 28% of the concentration of D3 in maternal blood. In subsequent work (B. Hollis, personal communication), that figure was shown to be closer to 32%, and a recent study by Oberhelman et al.64 showed a transfer fraction that can be calculated to be about 44%. Based on recommendations of both the American Academy of Pediatrics and the Institute of Medicine for infant intake (400 IU vitamin D/day, which requires a milk concentration of about 520 IU/L, i.e., ∼34 nmol/L), these transfer fractions would require a maternal serum vitamin D concentration of about 30–40 ng/mL (78–120 nmol/L). (The corresponding 25D concentration would be >50 ng/mL [125 nmol/L]; see Figure 8.) Hollis and Wagner59 estimate that the total input of D3 needed to maintain a milk concentration sufficient to meet the infant’s needs for vitamin D was approximately 6,000 IU/day. The equivalence value derived above produces a needed input of approximately 6,000 IU/day, which is essentially identical to the empirical estimate of Hollis and Wagner.
Dosing schedules and serum D3 concentrations
Dosing frequency for oral vitamin D supplementation regimens will affect serum concentration of D3 in predictable and often very striking ways. This fact has been largely overlooked to date, as the serum concentration of D3 has been generally considered to be of no particular interest in its own right. The rationale for infrequent (or bolus) dosing is that it leads to better adherence and that an excess amount ingested today will be stored in fat for use tomorrow. However, this assumption overlooks the effect of infrequent dosing regimens on D3 blood concentrations.
Serum D3 has a half-time variously estimated to be in the range of 0.5–3.5 days, with most investigators favoring a value of about 1.0 days. In contrast, D3 produced in skin moves into the blood with a half-time of about 3 days. This means that when skin synthesis is the principal source of D3, serum D3 concentration will be essentially constant around the clock, as D3 input to the blood from the skin (though produced mainly at mid-day) is effectively constant. With oral ingestion, intestinal absorptive input of D3 occurs mainly during a 4-h period following ingestion. (In one study, a TMAX of as much as 12 h was reported.65 As this is well beyond the usual mouth-to-cecum transit time, the 12-h figure, if confirmed, would suggest appreciable colonic absorption, or small bowel mucosal retention, or a delay pool in the intestinal lymphatics.) In any case, assuming a 1.0-day half-time, serum D3 concentration will inevitably follow a sawtooth pattern, particularly if oral ingestion is the principal input. Figure 10 displays the patterns for purely cutaneous input and for daily, weekly, and biweekly oral administration. With a once-a-week schedule, as is evident from Figure 10, serum D3 concentrations are close to zero for several days each week and below the reference level for most of the interdose interval. Thus, in the practical order, a nursing woman who takes her total weekly dose of vitamin D once each week would produce milk with little or no D content for roughly 4 of the 7 days in each week. This irregular delivery will be even more pronounced with biweekly or less frequent dosing schedules.
Figure 10
Calculated time courses for serum D3 concentration for varying oral dosing intervals. The reference level is the serum concentration for continuous (as contrasted with intermittent) dosing. Each dosing scheme provides the same cumulative intake, according to one of the following regimens: once daily, or 7 times the daily intake once weekly, or 14 times the daily intake once every 2 weeks.
It should be stressed that Figure 10 illustrates the concept and is not a depiction of actually measured serum concentrations of D3. Under input conditions in excess of daily use, unused D3 will accumulate in fat, and its concentration there would be predicted to damp the oscillations of D3 concentration in serum to some extent.
An additional feature of interval dosing is the high D3 concentration peaks achieved in the days following each dose. The impact of such high D3 levels is unclear, although Vieth66 has pointed to the induction of the 24-hydroxylation pathway as a likely consequence, with a corresponding reduction in effective vitamin D activity. Further, as the binding capacity of DBP is approximately 4.7 µmol67 (or ∼78,000 IU/L), with true Stosstherapie, as in several recent studies,68,69 the DBP will be fully saturated by the ingested D3, resulting in displacement of both 1,25D and 25D off DBP and into circulation as free or unbound moieties for several days after dosing (i.e., until fat uptake lowers serum D3 sufficiently). This effect amounts to a transient vitamin D intoxication of uncertain physiological import. Unfortunately, there is essentially no published information about vitamin D concentrations in the immediate post-dosing period following large bolus doses. Whatever else may be said of Stosstherapie, it certainly is not physiological.
Factors influencing serum 25D concentration
Aside from the possible importance of D3 concentration as the substrate for autocrine activity of vitamin D, there is general agreement that serum 25D concentration is currently the principal indicator of vitamin D status.70 This is because extrarenal conversion of 25D to 1,25D operates at concentrations below the kM for the tissue 1 -α-hydroxylases; hence, serum 25D concentration limits the amount of 1,25D a tissue can synthesize when its cells are stimulated to produce a vitamin D-dependent response. While there is no consensus as to the optimal serum 25D concentration, there is also no disagreement about the importance of the substrate, regardless of which concentration may be deemed optimal.
Input of D3, a factor that manifestly affects 25D concentration, has been the subject of much of the previous discussion. Attention is now focused on the effect on serum concentration of 25D produced by variations in body size and in D3 output, i.e., utilization and/or degradation of the 25D in serum.
Obesity
One widely recognized influence on 25D concentration is obesity, with serum 25D being lower in obese individuals. This was originally attributed to a phenomenon termed “sequestration” (implying trapping of vitamin D in adipose tissue of obese individuals).71 However, Drincic et al.72 have shown that simple volumetric dilution is both a more logical explanation and one that fully explains the weight-based difference. Curiously, body mass index works in various regression models almost as well as body weight (and somewhat better in some datasets). This is surprising as body mass index is not a measure of mass but of fatness. The reason is presently unclear, and this observation suggests the possible existence of further mechanisms operating in obese individuals.
Parathyroid hormone-1,25D axis Clements et al.60–62 showed that 25D half-time in serum ranged from 15 to >35 days, with 25D half-time being inversely related to parathyroid hormone concentration. The parathyroid hormone effect, noted both in patients with hyperparathyroidism and in animals subjected to calcium deprivation, was, in turn, mediated by serum 1,25D concentration. Why 25D utilization (or degradation) should rise in the face of calcium need is physiologically unclear, particularly as renal 1,25D synthesis is not as dependent on 25D concentration as the autocrine functions of vitamin D.
Inflammation. The other major influence on serum 25D concentration is inflammation. It has been reported that vitamin D status is reduced in the face of systemic inflammatory processes.73–78 For example, Duncan et al.75 reported an inverse correlation of 25D with serum C-reactive protein, with 25D being 40% lower as serum C-reactive protein rose from <5 mg/L to >80 mg/L. Autier et al.,79 in a metaanalysis of the several reports on this relationship, confirmed the existence of the association but attributed the reduced vitamin D status to underlying illness rather than to the inflammation itself. That conclusion may be partly correct, at least for some chronic illnesses, but it cannot apply to the many documented cases in which vitamin D status drops acutely across an inflammatory episode, as with total knee arthroplasty.73,77 In one case study, Henriksen et al.73 reported a 12% drop in 25D by day 2 after total knee arthroplasty and a nearly 80% drop by post-surgery week 8. Reid et al.77 evaluated a series of 33 patients who underwent total knee arthroplasty and reported an approximate 40% drop in total 25D and a 33% drop in calculated free 25D by day 2 after surgery, which was associated with large increases in C-reactive protein.
Decreases in 25D of this magnitude and rapidity cannot be explained by decreased synthesis and must, therefore, reflect increased utilization, degradation, or loss. Depending on which values may be estimated for the total 25D mass (see above), reductions in 25D concentration of the size reported by Reid et al. translate to a loss of several hundred micrograms from the body, which is substantially greater than ordinary daily utilization of vitamin D. While increased utilization cannot be ruled out, it seems unlikely to be the sole explanation. Another possibility, which was suggested by Waldron et al.,76 is the loss of DBP (with its bound ligand) in the urine. In 30 patients undergoing elective orthopedic surgery, the ratio of DBP to creatinine in urine rose 2.5× by the second day post-surgery; this was associated with a >20-fold increase in C-reactive protein. Renal loss could certainly explain much or all of the change in 25D observed in these studies and could be the result of interference with the kidney’s megalin–cubilin system, possibly produced by the anesthesia or inflammatory cytokines associated with the surgery.
Although not directly related to the major focus of this review, the conclusion reached by several of the authors of the studies just reviewed, i.e., that, while inflammation clearly reduced D status, this reduction was without nutritional significance, is in no way supported by data in any of the papers concerned, nor is it consistent with the importance of serum 25D concentration as the principal limiting factor in the autocrine pathway.
METABOLISM AND UTILIZATION the data assembled here make clear that, even with today’s widespread vitamin D inadequacy, total vitamin D inputs are far higher than previously thought, food sources are greater than previously recognized, and solar input, though theoretically capable of fully meeting any plausible vitamin D requirement, is actually only a minor present-day contributor to total vitamin D input at the population level. That does not mean that the human requirement is more easily met. Rather, it indicates that the requirement is higher than previously recognized, with populations still short of meeting that requirement by the amount needed to move prevailing serum 25D concentrations from current values to putatively healthier levels.
These analyses also make clear that at prevailing inputs (i.e., <4,000 IU/day), D3 is rapidly 25-hydroxylated and little D3 circulates in the blood or is shunted into adipose tissue for storage. Additionally, the recent recognition that oral 25D may raise serum 25D to a significantly greater extent than does oral vitamin D suggests the possibility of a hitherto little recognized or explored intracellular pathway in which the entire metabolic sequence is handled within certain target tissues and is not reflected in blood. A related finding in this respect is the importance of a maternal serum D3 concentration sufficient to support production of human milk capable of meeting infant needs for vitamin D.
Several of these insights have implications for the human requirement. For example, the vitamin D input needed to support an adequate amount of vitamin D in human milk has implications not just for lactation but also for human success as a species under presupplementation conditions. Inadequate vitamin D input in newborns would be expected to lead to skeletal abnormalities (for which the paleo-fossil record provides no evidence), in addition to possible consequences for immune system development.89 A total input of approximately 6,000 IU in modern humans equips them to feed their infants with a nearly full range of the nutrients needed for healthy growth.
CONCLUSION Precise quantification of vitamin D inputs, transfers, conversions, and compartment sizes are essential for a full understanding of how the human body utilizes this essential micronutrient, why it is important, and what the consequences are of an inadequate vitamin D input.
Since its founding, the U.S. Preventive Services Task Force (USPSTF) has provided firm evidential base for early detection strategies, evaluating such screening methods as mammography and prostate-specific antigen testing. Although it has also evaluated a few interventions, its predominant focus has been testing for markers that identify persons at risk who are likely to benefit from preventive action. Only recently has USPSTF entered the (mine)field of nutrition, a territory distant from screening tests and risk assessment, with different and unfamiliar landmarks.
The USPSTF now reports it is unable to find evidence for or against vitamin D deficiency testing (1), the likely reasons being the absence of a scientific consensus on both the level of vitamin D status that should be judged “deficient” and what the measurable manifestations of deficiency might be. These are also issues for many other nutrients, such as folate, ascorbate, calcium, and protein. Vitamin D may have seemed to offer a way out of this confusion because serum 25-hydroxyvitamin D [25-(OH)D] concentration is generally recognized as one of the best indices of status for any of a broad array of nutrients. Also, it is now readily measurable and widely utilized.
One of the reasons its promise has not been realized is that most studies of vitamin D efficacy have used a disease-avoidance model, which is the standard approach used by the Institute of Medicine (IOM) for most nutrients (2). Furthermore, disease prevention is the explicit focus of the USPSTF. Nevertheless, the IOM and USPSTF approaches effectively equate health with the absence of disease, an equivalence that nutritionists have long rejected. Instead, nutritionists focus on full nutrient repletion when possible. The inevitable gap between disease prevention and nutrient repletion is still largely unexplored territory. For many nutrients, it can be surprisingly wide, as suggested in this case by studies of the intake required to provide vitamin D in human breast milk in quantities sufficient to meet the needs of infants (3). The IOM’s adult requirement for vitamin D is 600 IU/d (4), which is judged to be sufficient to protect against osteoporotic fracture. In contrast, quantitative and empirical evidence indicates that vitamin D intake from breastfeeding needs to be approximately 6000 IU/d (3, 5). Although high compared with the adult recommendation, such an intake almost exactly reproduces the measured vitamin D status of contemporary Africans leading ancestral lifestyles (6). Such populations provide perhaps our best window on vitamin D levels prevailing during the millennia over which human physiology was adapted to its environment by natural selection.
Whatever the actual requirement or 25-(OH)D cutoff may be, there is another likely reason that the evidence is unclear. The USPSTF drew from systematic reviews and meta-analyses of studies of vitamin D effects, such as the one accompanying the current report (7). In general, the criteria for including studies in such reviews are methodological rather than biological. Of the 6 published biological criteria (8) for including published reports in meta-analyses, the review published in this issue met only 2 (comparable basal status and same chemical form), and several of its component studies met none. Including studies that could never have been informative in the first place (especially when they are large) inevitably biases any review toward the null.
What seems not to have been widely appreciated is that vitamin D exhibits flat response regions at both low and high values of vitamin D status, with a sharp rise in the approximate center of the physiologic range of 25-(OH)D values (8). Studies like the WHI (Women’s Health Initiative), which enrolled women with low vitamin D status values and used a vitamin D dose insufficient to move them into the response range, provide little useful information about vitamin D efficacy. Yet, precisely such studies were included in the review by LeBlanc and colleagues (7). This is not to criticize the WHI, which was designed more than 20 years ago (before vitamin D pharmacology was well-understood), but it is to criticize contemporary reviews and meta-analyses that fail to take advantage of newer information or to use critical biological criteria (8) for selection of studies for analysis of biological effects.
In addition, a disease-avoidance approach becomes problematic for micronutrients in general (and vitamin D in particular) when one understands that micronutrients do not actually cause any of the effects simplistically attributed to them. Although necessary for cell response, such micronutrients by themselves do not initiate or cause the response concerned. For example, vitamin D is a component of the biochemical apparatus that opens the genome to allow access to DNA information needed for a particular cell or tissue response. In terms of cell function, this dependence means that when supplies of the micronutrient are inadequate, cellular response is blunted. This is dysfunction, but not clinically manifest disease. Such dysfunction may indeed lead ultimately to various diseases, but disease prevention remains a dull tool for discerning the defect, and a disease-prevention approach clearly does not measure whether the organism has enough of the nutrient to enable appropriate physiologic responses, such as lactation.
Finally, and aside from the USPSTF’s findings, one must ask whether treating without first testing is sound practice. Certainly, it would be rational to do so if the condition being treated is prevalent and the treatment is safe and inexpensive. That is the case with another micronutrient, iodine, and the iodination of salt. However, the current situation is different because getting sufficient iodine generally does not require conscious adherence to a particular regimen, whereas taking vitamin D does. Usually, testing improves patient adherence because it provides patient-specific, personally applicable information. General assurances that one probably needs extra vitamin D are not as compelling a motivator as knowing one’s number. Thus, whether the practitioner adheres to the widely divergent guidelines of the IOM (4), the Endocrine Society (9), or the American Geriatrics Society (10), measuring vitamin D status seems to be warranted, not so much to diagnose deficiency but to determine patient status relative to the selected guideline.
THE NEAR-IMPOSSIBILITY OF OVERDOSING WITH VITAMIN D3 – except by persistent repeated injection: A Report in Feb 2014 from Bansai & Arora ea New Delhi show how extreme the overdose of vitamin D3 must be to cause hypercalcemic toxicity: an Asian woman given 6million iu imi over 10 days after knee surgery presented 2 months later with 6 wks of persistent vomiting, fatigue, with moderate hypercalcemic renal failure and 25OHvit D level of 150ng/ml; that normalized in 2 weeks.. So her peak level after the initial 2 weeks on an average ~50 000iu/day may have been around 500-600ng/ml.. Bansai and Arora quote two series from endemically vit D deficient Kashmir (Pandita ea 2012 in Jammu and 2011 Koul ea Srinagar) of a total 25 elderly given chronic overdoses D3 600 000iu monthly , who were found to have similar moderate hypercalcemia and renal failure with peak 25OHvit D of 100 – 300ng/ml: a mean vit D3 dose of between 20 000iu and >1million iu/day?, mean s. creat 2.5; mean 25OHvitD of 100 – 200ng/ml; mean calcium 13.1mg/dl. 20 000iu a day indefinitely in these frail small elderly averages at least 400iu/kg/day, at least 5 times the chronic recommended dose in the literature the past decades- and to boot, routinely given them with a highdose calcium supplement- when it is rather magnesium that should if any be boosted. . Koul ea do note that about 100 000iu vit D a day ongoing is required to cause hypercalcemia, the mean lethal dose being about 8million iu.
By contrast, previous reports below- eg from the Netherlands report of 2million iu single overdose in 90 year olds; and planned 600 000iu orally monthly dose in Pakistani men wasted with TB (Salhuddin ea below) showed no overdose signs. So a single loading dose of 1 to 2 million units is unlikely to give overload. By these precedents (eg 600 000iu p.o monthly- apparently official policy of the Pakistani Endocrine Society) one may in acute infections give up to 600 000iu as a loading dose (a million in an obese ill patient) in acute infection situations, then 50 000- 80 000iu weekly depending on weight, to maintain level around 90ng/ml.
Am J Clin Nutr March 2008 Pharmacokinetics of a single, large dose of cholecalciferol 100 000iu Ilahi, Armas, and Heaney Creighton University Medical Center, Omaha, Design: followed for 4 mo, 30 subjects were supplemented with a single oral dose of 100 000 IU cholecalciferol. 10 subjects served as a control group to assess seasonal change of calcidiol. The subjects were healthy with limited sun exposure (<10 h/wk) and milk consumption (<0.47 L daily); excluded granulomatous conditions, liver disease, kidney disease, or diabetes or taking anticonvulsants, barbiturates, or steroids. Results: Serum calcidiol rose promptly after cholecalciferol dosing from a mean (±SD) baseline of 27.1 ± 7.7 ng/mL to a concentration maximum of 42.0 ± 9.1 ng/mL. Seven percent of the supplemented cohort failed to achieve 32.1 ng/mL at any time point. The highest achieved concentration in any subject was 64.2 ng/mL. The control group had a nonsignificant change from baseline of −0.72 ± 0.80 ng/mL during 4 mo. Conclusions: Cholecalciferol (100 000 IU) is a safe, effective, and simple way to increase calcidiol concentrations. The dosing interval should be ≤2 mo to ensure continuous serum calcidiol concentrations above baseline.
THE IMPORTANCE OF IMMUNOSYNERGY BETWEEN ADEQUATE ANABOLIC HORMONES- VIT D3, MELATONIN (Berman 1926, Carrillo-Vico 2013), AND PROGESTERONE in planned and current pregnancy, and aging? Thangamani, Kim ea Purdue & Indiana Universities in J Immunol. 2014 Dec 29: Cutting Edge: Progesterone Directly Upregulates Vitamin D Receptor Gene Expression for Efficient Regulation of T Cells by Calcitriol. The two nuclear hormone receptor ligands progesterone and vit.D play important roles in regulating T cells.., we report that progesterone is a novel inducer of vit.D receptor (VDR) in T cells and makes T cells highly sensitive to calcitriol even when vit. D levels are suboptimal. This novel regulatory pathway allows enhanced induction of regulatory T cells but suppression of Th1 and Th17 cells by the two nuclear hormones. The results have significant ramifications in effective regulation of T cells to prevent adverse immune responses during pregnancy.
A recent review of vitamin D from Mike Holick (Boston Mass.) and a German team again reminds us of two opposing forces limiting natural sunshine vitamin D supply: on the one hand the skin shuts down active vit D production if the sunlight burns, while on the other, there is simply not enough sunlight beyond 35degrees latitude from the equator. Thus Germany and Canada-northern USA for example, at >45degrees north, get far too little sunlight for vit D needs ; eg London is at 51degrees north; Cape Town-Florida-San Diego, Sydney-Buenos Aires, Hawai and the Med. countries are at the 35degree south latitude. Even this close to the equator, many overdress- especially more observant religious women- and thus minimize benefit from summer sunshine.
J Assist Reprod Genet. 2014 Dec 30.Vitamin D and assisted reproduction: vitamin D should be routinely screened and repleted prior to ART? Pacis , Segars ea Dartmouth-Hitchcock Medical CenterLebanon NH systematic review. review current literature regarding the role of vitamin D status & repletion in pregnancy outcomes in women undergoing assisted reproductive technology (ART). Thirty-four articles were retrieved, of which eight met inclusion criteria. One study demonstrated a negative relationship between vitamin D status and ART outcomes, two studies showed no association. The remaining five studies concluded that ART outcomes improved after vitamin D repletion.The majority of reviewed studies reported a decrement in ART outcomes in patients with vitamin D deficiency. Cost-benefit analyses suggested that screening and supplementing vitamin D prior to ART might be cost effective.
25 Dec 2014 ANOTHER AVOIDABLE TRAGIC TB DEATH: Dr Nerissa Pather and countless other infectious disease sufferers – health workers and their patients :
Sunshine Cures: why did TB sanatoria work (before there were antibiotics)? was it indeed the boost of copious sunshine secosteroid antimicrobial soltriol in the skin destroying the M TB porphyrins? or was it belief, then-cleaner air, high altitude, rest, care and better nutrition?
Not for nothing was skin ie CTB Lupus Vulgaris a relentless scourge in the clothed in darker climes and times, except perhaps in ancient sunny Pharanoic medicine, until the Danish Faroe Islander physician Niels Finsen- trying to treat his own Niemann–Pick disease– used his invention phototherapy generator on his patients and found that it magically rolled back skin TB (for which in 1903 he got the only Nobel prize apparently ever awarded for dermatology!). This light therapy antimicrobial effect has recently 2005 been attributed by Danish researchers Møller, Wulf ea to the lethal effect of light oxidation on Mycobact TB porphyrins. However, this Danish study abstract ignores the antimicrobial benefit of cholecaliferol activated by light on the skin from the Karolinska Inst in Sweden. A Georgetown Univ paper 2005 details the complexities of Sunlight, Vitamin D, and the Innate Immune Defenses of the Human Skin , further set out in Optimal Skin Protection with Vitamin D. Unfortunately the circle is not yet squared off, there is still no study showing that vitamin D (like bcarotene and likely melatonin) improves the disease porphyria?
A recent 2009 Mt Sinai NY report of a case of CTB cutaneous TB stresses how rare this skin complication is despite the increasing spread of TB with AIDS- perhaps partly because of the higher prevalence of HIV in poorer peoples in sunnier warmer ie relatively better sunshine-cholecalciferol-endowed climates.
We easily make our optimal vit D3 ~100iu/ kg per day living playing and working outdoors in warm lands. But since we dress more in cooler climates, with aging and dress-conservative cover-up tribal eg Arabic and Hasidic and Mormon customs; and avoid sunburn, and from early middle age lose 3/4 of our skin vitamin D production by 70years, we aging thus need the bulk of our vit D requirements as supplements ie ~7000iu/day or 50 000iu/week.
A century ago, TB, polio, measles, scarlatina, and syphilis were rampant, and infections rather than wars killed most – ending in the 1919 flu holocaust that devastated the family of Dr Sir Arthur Conan Doyle (whereas the Flu pandemic took just one of my parents’ score of siblings- and polio just left my Mom with a limp..)..
2014 is the centenary of recent recognition of the cod liver oil antirickets steroid factor – calciferol/soltriol -briefly misnamed “vitamin” D – by McCollum, Davis (USA 1913) and Mellanby(UK); so that in 30 years by 1945, rickets had been all but abolished in USA. But the recognition of the antirachitic factor was facilitated by discovery in the preceding decade of vitamins A, B and C. The antiscurvy benefit of fresh uncooked coloured crops (and thus their juice) had indeed been recognized for millennia – eg the Royal Navy limejuice- , but a specific micronutrient vitamin deficiency was first only recognized in 1907. Vitamin C ascorbic acid identification also took another 25years . For 90 years, it has been recognized that a lightly cooked exclusively fatty meat diet can provide enough vitamin C (let alone all micronutrients) for health in eg atheroma- and scurvy-free Eskimos and anyone who cares to eat thus (Stefansson ) .
Sadly, the lifegiving vitamins have been diluted, all but eliminated from retail bottled codliver oil, a ml of which now generally supplies perhaps only 125iu vit D, and vitamin A 1000iu … So even a tablespoon supplies only about 1200iu vit D.. The Weston Price Foundation discusses why modern commercial codliver oil is good with its balance of vits A and D– but the vitamin D level is still far too low for cooler darker countries. However we recommend, (apart from far cheaper vit D3 powder 50 000iu/1ml scoop) – a tsp cod liver oil at least 3 times a week because it is the cheapest natural- and with Scandinavian manufacturing controls, safe- source of vital EPA+DHA available as well as some vitamins A and E.
As real summer begins here between the southern oceans, cold winter in the northern hemisphere, we must constantly remind that vitamin D3 cholecalciferol is NOT an exogenous vitamin ie a biological nutrient essential (Funk’s ‘vitamine’, shortened by Jack Drummond because they are not amines to the more appropriate ‘vitamin’) in the human diet ( like vits A, B, C, E & K) because humans cannot make them. . But since we make vit D with light exposure of our skin, since most humans dont get enough sunlight on our skin, it is certainly a conditioned essential anabolic steroid, which like other anabolic steroids (the balance especially of androgens) is vital at optimal blood levels through life for optimal health, healthspan.
Unlike the real vitamins and essential minerals, Calciferol is (like eg CoQ10, alphalipoic acid, nitric oxide, EPA and DHA) made in limited quantities in humans with adequate organ function and sunshine; but none of them generally in anywhere near optimal quantities for healthspan against all diseases. So given humans’ capacity to live well to a century, we need such supplements from youth to ensure chronic health so as to die of old age in good health. .
How does this relate to the death this month of Dr Nerissa Pather? Multiresistant TB contracted on duty 12 years ago eventually killed her, whether or not such high-risk people are ever advised to take the best prevention- zinc, selenium, multivites but especially highdose vit C and D3.
D3 bio-insufficiency fragility and dysimmunity is further complicated since to correct it requires both plenty of skin sunshine exposure, eaten vitamin C and it’s daughter cholesterol, and optimal kidney and liver function. Even then optimal vitamin D3 bloodlevel and effect may be blocked by foolhardy cholesterol blockade eg statins, and by excess intake and thus bloodlevel of vitamin D2 ergocalciferol – which authorities eg in South Africa and USA still negligently promote/ dispense as the dangerously misnamed “strong calciferol”. It is indeed D3 cholecalciferol, not D2 that is the miracle sunshine strong calciferol steroid; egocalciferol dominance, like insulin and estrogen dominance, is harmful, and can and must be avoided. .
So it is increasingly apparent that, just as intake/manufacture of vitamin C the true sunshine vitamin (those colourful veg/ fruit orchards etc) , and thence cholesterol, should each be at least a few gms a day, the human (clothed indoor-dwelling) adult synthesis + intake of sunshine hormone vitamin D3 soltriol should be nearer to 10 000iu ie 250mg/day, or more practically 50 000iu vit D3 a week (at a trivial supplement cost of eg R6/month or $5 a year) for a bigger adult- especially in longer darker winter (starting with perhaps about 25000iu every fortnight for babies) .. of course balanced in most societies with the other supplements especially water, vitamin K2, zinc, selenium iodine and magnesium (and iron for children and reproductive mothers) .
So, how many more millions must suffer and die from lack of the cheapest, best, safest conditioned essential antimicrobial antioxidant anabolic nutrients available?
An undated (post 2003) Pharmacology Bulletin from Canterbury NZ at least gives conservative realistic vit D3 advice: a loading dose of D3 500 000iu , then 50 000iu/month. This compares with our routine loading dose of about 200 000 to 400 000iu to start, then 50 000iu every week or two (proportionate to body mass and illness). But Lennons here negligently still continues to advertise their Strong Calciferol datasheet (updated 2004) as calciferol- last year they in fact confirmed it is D2 ergocalciferol, not cholecalciferol. Only their website http://www.ndrugs.com/?s=lennon-strong%20calciferol confirms that their strong Calciferol is D2; whereas they also make low strength D3 tabs.
From today’s press “The South African Medical Association (SAMA) extends heartfelt condolences on the passing of 38yr old Dr Nerissa Pather on 18th December 2014 . Whilst on community service at a Kwazulu Natal clinic, Dr Pather contracted well-publicised multi-drug resistant spinal TB in 2002 , that rendered her paralyzed and in constant pain. The loss to a communicable disease acquired in the course of duty is an incalculable tragedy. SAMA reiterates its call to all health departments and facilities to ensure that basic TB prevention methods are available to all healthcare workers in our facilities. Sadly, this is not the case in many of our hospitals and clinics and continues to place health professionals at enormous risk. The potential consequences of infection and even acquiring drug resistant TB are tragically evident in the death of Dr Pather. SAMA bows its head to a colleague who has paid the ultimate price in caring for her fellow human beings.”
A current report from Tehran Calcium and vitamin D plasma concentration and nutritional intake status in patients with chronic spinal cord injury: stresses the obvious, the terribly low intake and levels of vitamin D in spinal cord injury patients. Why are we inflicting this further deprivation on the most vulnerable patients?
The tragedy is that with general authoritarian nihilism about universal vitamin supplements- some calling their promotion quackery- unrecognized deficiency eg vit D3, rickets, and vit C scurvy are on the increase even in the more affluent eg USA and in sunnier climates- especially with increasing geriatrics and the frail surviving with eg HIV, TB, cancer, chronic bowel disease, gross overuse of warfarin (vit K deficiency) and statin (CoQ10 deficiency) etc. .
Vitamin D Deficiency in Critically Ill Patients is rarely considered or treated .. N Engl J Med 2009 Lee, Eisman & Center studied vitamin D status in ICU patients referred to St. Vincent’s Hospital, Sydney in 2007. Among approximately 1100 ICU patients per year, the mean 25-hydroxyvitamin D in 42 referred patients was ~17ng per milliliter, with a high prevalence of hypovitaminosis D . Moreover, three patients died (from metastatic thymic carcinoma, glioma, and lymphoma), and had undetectable levels of 25-hydroxyvitamin D. The current study of ICU patients reveals high prevalence of hypovitaminosis D that was associated with adverse outcomes, independently of hypocalcemia and hypoalbuminemia. Supplementation with vitamin D (at a mean dose of 820 IU per day) before admission was not protective. Vitamin D deficiency is associated with increased mortality.However, vitamin D has pleiotropic effects in immunity, endothelial and mucosal functions, and glucose and calcium metabolism. The association between hypovitaminosis D and common conditions (e.g., the systemic inflammatory response syndrome, septicemia, and cardiac and metabolic dysfunctions) in critically ill patients may be important. Vitamin D–deficient and vitamin D–insufficient states may worsen existing immune and metabolic dysfunctions in critically ill patients, leading to worse outcomes. A total of 17% of ICU patients in our study had undetectable levels of vitamin D. hypocalcemia was identified as a reason for referral in only 5% of the patients. These findings highlight the need for consideration of vitamin D status and supplementation in patients in the ICU.
Arch Intern Med. 2008;168:1629-37 25-hydroxyvitamin D levels and risk of mortality in the general population. Melamed , Astor ea. Albert Einstein College of Medicine, NY tested the association of low 25(OH)D levels with all-cause, cancer, and cardiovascular disease (CVD) mortality in 13 331 nationally representative adults 20 years or older from the NHANES III linked mortality files. In patients on dialysis, therapy with vitamin D agents is associated with reduced mortality. Observational data suggests that low (25[OH]D) are associated with diabetes mellitus, hypertension, and cancers. However, whether low serum 25(OH)D levels are associated with mortality in the general population is unknown. Participant vitamin D levels were collected from 1988 through 1994, and individuals were passively followed for mortality through 2000. RESULTS: In cross-sectional multivariate analyses, increasing age, female sex, nonwhite race/ethnicity, diabetes, current smoking, and higher body mass index were all independently associated with higher odds of 25(OH)D deficiency (lowest quartile of 25(OH)D level, <17.8 ng/mL , while greater physical activity, vitamin D supplementation, and nonwinter season were inversely associated. During a median 8.7 years of follow-up, there were 1806 deaths, including 777 from CVD. In multivariate models , compared with the highest quartile, being in the lowest quartile (25[OH]D levels <17.8 ng/mL) was associated with a 26% increased rate of all-cause mortality (mortality rate ratio, 1.26; 95% CI, 1.08-1.46) and a population attributable risk of 3.1%. The lowest quartile of 25(OH)D level (<17.8 ng/mL) is independently associated with all-cause mortality in the general population.
ANABOLIC STEROID SYNERGY?: the steroids cholecalciferol and androgen are both immune and anabolic -switch protein/muscle/bone promoters, without apparent mutual antagonism or suppression; calciferol also lowers SHBG levels, freeing up more active unbound testosterone ie reducing estrogen dominance.
Subst Abuse Rehabil. 2014 Dec 10;5:121-7. Effects of different doses of testosterone on gonadotropins, 25-hydroxyvitamin D3, and blood lipids in healthy men. Gårevik, Ekström ea. At the Karolinska Inst Sweden, Twenty-five healthy male volunteers aged 27-43 years were given 500 mg, 250 mg, and 125 mg of testosterone enanthate as single intramuscular doses. All doses investigated suppressed the LH and FSH concentrations in serum. LH remained suppressed 6 weeks after the 500 mg dose. These results indicate that testosterone has a more profound endocrine effect on the hypothalamic-pituitary-gonadal axis than was previously thought. There was no alteration in 25-hydroxyvitamin D3 levels after testosterone administration compared to baseline levels. The 250 and 500 mg doses induced decreased concentrations of ApoA1 and HDL, whereas the lowest dose (125 mg) did not have any effect on the lipid profile.
Pediatrics. 2014 Dec . Rapid Normalization of Vitamin D Levels: A Meta-Analysis. McNally. Menon ea @Univs Ottowa, Thailand & Ireland systematically reviewed pediatric clinical trials administering high-dose vitamin D to evaluate (25[OH]D) response and characteristics of final 25(OH)D levels . Uncontrolled and controlled trials reporting 25(OH)D levels after high-dose (≥1000 IU) ergocalciferol or cholecalciferol were selected. Two of 6 studies that administered daily doses approximating the Institute of Medicine’s Tolerable Upper Intake Level (1000-4000 IU) to vitamin D-deficient populations achieved group 25(OH)D levels >75 nmol/L within 1 month. Nine of 10 studies evaluating loading therapy (>50 000 IU) achieved group 25(OH)D levels >75 nmol/L. In meta-regression, baseline 25(OH)D, regimen type, dose, age, and time factors were associated with final 25(OH)D levels. Adverse event analysis identified increased hypercalcemia risk with doses >400 000 IU, but no increased hypercalcemia or hypercalciuria with loading doses <400 000 IU (or 10 000 IU/kg). Few studies in adolescents evaluated loading dose regimens >300 000 IU.
CONCLUSIONS: Rapid normalization of vitamin D levels is best achieved by using loading therapy that considers disease status, baseline 25(OH)D, and age (or weight).
Diabetes Res Clin Pract. 2014 Dec A randomised controlled trial of ‘high” dose vitamin D in recent-onset type 2 diabetes .Elkassaby, Fourlanos ea, Melbourne Australia. Vitamin D insufficiency is associated with impaired pancreatic beta-cell function. Fifty adults with type 2 diabetes diagnosed less than 12 months, with normal baseline serum 25-OH D (25D), were randomised to 6000IU D (n=26) or placebo (n=24) daily for 6 months. In the D group, median serum 25D (ng/ml) increased from 24 to 60 (3 months). change in FPG (mmol/l) was significantly lower in D (-0.40) compared to placebo (+0.1) (P=0.007), as was the change in PPG in D (-0.30) compared to placebo (+0.8) (P=0.005). Change in HbA1c (%) between D (-0.20) and placebo (-0.10) was not different (P=0.459). At 6 months, changes from baseline in DCP, FPG, PPG and HbA1c were not different between groups. ie modest Oral D3 supplementation in type 2 diabetes was associated with transient improvement in glycaemia, but without a measurable change in beta-cell function. this effect is unlikely to be biologically significant. This modest dose D3 ie 42000iu/ week to eventual bloodlevel of only 50ng/ml therefore appears to offer little or no therapeutic benefit in type 2 diabetes. THE DOSE THEY USED IN FACT PRODUCED STEADYSTATE VIT D3 LEVEL HALF THE POSTULATED TARGET LEVEL OF 90-100 ng/ml FOR SERIOUS ILLNESS.
J Asthma. 2014 Nov Efficacy of high-dose vitamin D in pediatric asthma: a systematic review and meta-analysis.
Pojsupap , McNally ea Univ Ottowa : studies suggest a relationship between vitamin D status and asthma-related respiratory outcomes. benefit of vitamin D supplementation for pulmonary function, symptoms and exacerbations is not well established. Clinical trials reporting asthma-related respiratory outcomes following vitamin D administration at a dose equal or greater than 500 IU per day were included. Results: five studies met study eligibility and assessed final data synthesis. The median trial size was 48 participants (range 17-430) and the average daily dose of cholecalciferol ranged from 500 to 2000 IU/day. Meta-analysis suggested a statistically significant reduction (RR 0.41, CI 0.27-0.63) in asthma exacerbation with vitamin D therapy.
J Infect Dis. 2013 Feb . Vitamin D status and incidence of pulmonary tuberculosis, opportunistic infections, and wasting among HIV–infected Tanzanian adults initiating antiretroviral therapy. Sudfeld, Fawzi ea . Maintaining vitamin D sufficiency may decrease the incidence of pulmonary tuberculosis and other infectious diseases. We present the first prospective study of vitamin D among human immunodeficiency virus (HIV)-infected adults receiving antiretrovirals in sub-Saharan Africa. Serum 25(OH)D level was assessed at antiretroviral therapy (ART) initiation for 1103 HIV–infected adults enrolled in a trial of multivitamins (not including vitamin D) in Tanzania.After multivariate adjustment, vitamin D deficiency (defined as a concentration of <20 ng/mL) had a 3 fold significantly greater association with incident pulmonary tuberculosis, compared with vitamin D sufficiency (HR, 2.89; [CI], 1.31-7.41; P = .027), but no association was found for vitamin D insufficiency (defined as a concentration of 20-30 ng/mL; P = .687). Deficiency was also significantly associated with incident oral thrush (HR, 1.96; 95% CI, 1.01-3.81; P = .046), wasting (HR, 3.10; 95% CI, 1.33-7.24; P = .009), and >10% weight loss (HR, 2.10; 95% CI, 1.13-3.91; P = .019). Wasting results were robust to exclusion of individuals experiencing pulmonary tuberculosis. Vitamin D status was not associated with incident malaria, pneumonia, or anemia.
BoneKey Rep 2014:3:479:p1-8 History of the discovery of vitamin D and its active metabolites Prof Hector deLuca graphically tells the story of the discovery of the lifesaving sun steroid cholecalciferol D3 between 1913 and its chemical formula in 1937, and then its’ functional chemistry through the 1970s. Until the preWW1 era, nutrition was blocked by false German dogma (von Liebig ea) that an adequate diet consisted of just 12% protein, 5% mineral, 10–30% fat and the remainder as carbohydrate. Such a diet – eg with polished rice, sugar and milled wheat- was shown to rapidly kill humans and animals ie without the essential micronutrient vitamins. .
Belief that this defined an adequate diet was to resurface in postWW2 Western capitalism in USA and UK through the twentieth century.
Then British, Continental and USA nutritional scientists started tearing that myth apart- and today we have the revelation that we need the ancient diet: just an adequate amount of first-class protein (but not soya); the bulk of needed nutritional calorie energy as natural fat (balanced omega 3: omega 6 and saturated medium chain triglycerides, but not transfats which are synthetic), with the balance of energy carbs and protein supplied by coloured veggies; supplying enough of the essential minerals, vitamins and marine oils.
But since most humans are no longer able to live off unpolluted unfarmed marine life or natural rotation-crop and grazed meat farming, but work indoors during daylight hours or, worse, disruptive night shifts, and city deathrates have risen steadily on the mythical low(but synthetic) fat, high carbs diet invented as dogma by Ancell Keys and his food factory cronies, the natural fat and -coloured-veggs -dominant diet rapidly re-establishes itself, with vigorous vit D3 and multivits to supplement the depleted and polluted fastfood chain.
update 22 Dec 2014: as the solstice rolls by, infections especially viral flourish north and south, from flu to gastro , HIV to ebola; HPV to HZV to childhood exanthems;
so more reason to aim for optimal growth, mental and physical health with the peak anabolic antidepressant energizing anticancer antiinfective steroid – cholecalciferol D3 – intake and levels. About 65 000iu a week (with my multivit-multimineral combo) puts my measured trough 25OHvit D bloodlevel at 92ng/ml with normal blood calcium. Women can live long without much androgen apart from frail bones, but not well without vigorous cholecalciferol D3 intake. Humans who live mostly bare mostly outdoors- us naked apes- most of the year closer to the equator make plenty of D3 from sunshine; but the darker our skins, the sooner vit D production shuts down; so most of us need vigorous D3 supplement costing perhaps US$6 a year retail. .
update 19 Nov 2014 when this column on vit D started 5 years ago, there were 46000 vit D entries on Pubmed- this has mushroomed 40% to 61000 (compared now to 46000 on vit A; to 53000 on vitamin C; 37000 on vitamin E; 17000 on vit K; and 133000 on all the 8 B vitamins ); whereas in 2009 there were 272500 entries on all vitamins– now up only 22% to 335 000. ie the papers on the secosteroid vitamin D have risen at double the rate of the vitamins.. (D3 C27H44O and D2 C28H44O, vs testosterone C19H28O2).
As the end-of-year solstice approaches, its time to review the crucial role of giving vigorous doses of vitamin D3, whether via non-burn sunshine, or via the correct lowpressure tanning bed, or directly as vitamin D3 (not vit D2) supplement as appropriate TOGETHER WITH A MULTINUTRIENT PLUS EXTRA MAGNESIUM AND VIT K2. . Ironically, dermatologists would recommend vit D supplement not suntan for what many consider the wrong reason- that suntanning does more harm than good, which it doesnt. :
at least THIRTEEN VIT D studies the past 16 years SINCE 1998, from ~8 nations- USA, Canada, Belgium, Spain , Germany, Denmark, UK & New Zealand, – show POORER RESULTS FROM TAKING TOO LITTLE VIT D; OR FROM USING VITAMIN D2 not D3, apparently by suppressing the crucial vit D3 level, and because vit D2 is metabolized faster. :
a new OBSERVATIONAL study in Am J Clin Nutr. Nov 2014 from the Cambridge EPIC-NORFOLK group by Kay-Tee Khaw, Nicholas Wareham ea Serum 25-hydroxyvitamin D, mortality, and incident cardiovascular disease, respiratory disease, cancers, and fractures: a 13-y prospective population study examined prospective relation between serum [25(OH)D] concentrations [which comprised 25(OH)D3 and 25(OH)D2] and subsequent mortality in 14,641 men and women aged 42–82 y in 1997–2000 in Norfolk, UK followed up to 2012; categorized into 5 groups according to baseline serum concentrations of total vit D from below 30nmol/L to above 90nmol/L.. mean serum total 25(OH)D was 56.6 nmol/L 22ng/ml, which consisted predominantly of 25(OH)D3 (mean: 56.2 nmol/L; 99% of total). The age-, sex-, and month-adjusted HRs for all-cause mortality (2776 deaths) for men and women by increasing vitamin D category were 1, 0.84 (0.74, 0.94), 0.72 (0.63, 0.81), 0.71 (0.62, 0.82), and 0.66 (0.55, 0.79) (P-trend < 0.0001). When analyzed as a continuous variable and with additional adjustment for body mass index, smoking, social class, education, physical activity, alcohol intake, plasma vitamin C, history of cardiovascular disease, diabetes, or cancer, HRs for a 20-nmol/L increase in 25(OH)D were 0.92 (0.88, 0.96) (P < 0.001) for total mortality, 0.96 (0.93, 0.99) (P = 0.014) (4469 events) for cardiovascular disease, 0.89 (0.85, 0.93) (P < 0.0001) (2132 events) for respiratory disease, 0.89 (0.81, 0.98) (P = 0.012) (563 events) for fractures, and 1.02 (0.99, 1.06) (P = 0.21) (3121 events) for incident total cancers. Conclusions: Plasma 25(OH)D concentrations predict subsequent lower 13-y total mortality and incident cardiovascular disease, respiratory disease, and fractures but not total incident cancers. For mortality, lowest risks were in subjects with concentrations >90 nmol/L ie 36ng/ml, and there was no evidence of increased mortality at high concentrations, suggesting that a moderate increase in population mean concentrations may have potential health benefit, but <1% of the Norfolk population had concentrations >120 nmol/L 48ng/ml.
Chowdhury , Franco ea also University of Cambridge, UK. BMJ. 2014 Apr . Vitamin D and risk of cause specific death: systematic review and meta-analysis of observational cohort and randomised intervention studies. Study specific relative risks from 73 cohort studies (849,412 participants) and 22 randomised controlled trials (vitamin D given alone versus placebo or no treatment; 30,716 participants). In the primary prevention observational studies, comparing bottom versus top thirds of baseline circulating 25-hydroxyvitamin D distribution, pooled relative risks were 1.35 (95% confidence interval 1.13 to 1.61) for death from cardiovascular disease, 1.14 (1.01 to 1.29) for death from cancer, 1.30 (1.07 to 1.59) for non-vascular, non-cancer death, and 1.35 (1.22 to 1.49) for all cause mortality. Subgroup analyses in the observational studies indicated that risk of mortality was significantly higher in studies with lower baseline use of vitamin D supplements. In randomised controlled trials, relative risks for all cause mortality were 0.89 (0.80 to 0.99) for vitamin D3 supplementation and 1.04 (0.97 to 1.11) for vitamin D2 supplementation. The effects observed for vitamin D3 supplementation remained unchanged when grouped by various characteristics. However, for vitamin D2 supplementation, increased risks of mortality were observed in studies with lower intervention doses and shorter average intervention periods.
in a systematic review and meta-analysis– Tripkovic ,, Lanham-New ea . Univ Surrey Am J Clin Nutr. 2012 . Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: In the collective 10 studies, 1016 participants aged 18–97 yrs, men to women ∼1:3; vitamin D3 had a significant and positive effect in the raising of serum 25(OH)D concentrations compared with vitamin D2 (P = 0.001). When the frequency of dosage administration was compared, there was a significant response for vitamin D3 when given as a BOLUS dose (P = 0.0002) compared with administration of vitamin D2, but the effect was lost with daily supplementation.. The studies were in the United States, Canada, United Kingdom, Australia, Denmark, and Italy; all studies were single-center studies. Seven studies were conducted in healthy, free-living participants (4, 6, 7, 12, 13, 15, 17);
WE so far FIND AT LEAST 12 RELEVANT COMPARATIVE VIT D3/D2 TRIALS in humans and one in cows:
1. Karen Hansen ea at Univ Wisconsin 2014 An evaluation of high-dose vitamin D for rheumatoid arthritis show that giving vitamin D2 (not D3) 50 000iu fortnightly for a year is actually adverse – IT DEPRESSES – perhaps halves – THE BIOLOGICALLY ACTIVE blood 25OHVIT D3 while boosting perhaps 5 fold the far less active blood 25OHvit D2 levels , and actually worsens rheumatoid arthritis clinically and serologically .
2. Vitamin D2 supplementation amplifies eccentric exercise-induced muscle damage in athletes. Nutrients. Nieman , Luo EA. A, North Carolina 2013:6:63-75. Six weeks vit D2 (3800 IU/day) increased serum 25(OH)D2 fourfold and decreased 25(OH)D3 by a fifth versus placebo (p<0.001, p=0.036, respectively), with no influence on muscle function test scores, AND worsened muscle damage .
3. Swanson, Barrett-Connor, ea USA & Belgium May 2014 : In a cohort of older men, Higher 25(OH)D2 is associated with lower 25(OH)D3 and 1,25(OH)2D3 , suggesting that vitamin D2 may decrease the availability of D3 and may not increase calcitriol.
4.Lehmann, Dierkes ea Germany 2013 in the same leading scientific journal Bioavailability of vitamin D(2) and D(3) in healthy volunteers, a randomized placebo-controlled trial- giving vit D2 2000iu/day for 8 wks in healthy volunteers actually halves the crucial 25hydroxy vit D3 level; whereas giving vit D3 2000iu/d doubles the vit D3 level. Earlier studies have suggested that vitamin D2 is less biologically active than vit D3.
5. Biancuzzo, Holick ea Boston Mass. 2013 Serum concentrations of 1,25-dihydroxyvitamin D2 and 1,25-dihydroxyvitamin D3 in response to vitamin D2 and vitamin D3 supplementation in healthy adults 18 to 79 years consuming 1000 IU vitamin D2 or vitamin D3 per day for 11 weeks at end of winter was analyzed. Of the adults, 82% were vitamin D insufficient (serum 25-hydroxyvitamin D [25(OH)D <30 ng/mL]) at the start of the study. Administration of vitamin D2 and vitamin D3 induced similar increases (from baseline ~20ng/ml 25OH vit D) in total 25(OH)D as well as in 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3, respectively. Compared with placebo and adjusting for baseline levels, 1000 IU daily of vitamin D2 was associated with a mean increase of 7.4 pg/mL (95% confidence interval, 4.4-10.3) in 1,25(OH)2D2, and decrease of 9.9 pg/mL (-15.8 to -4.0) in 1,25(OH)2D3. No such differences accompanied administration of 1000 IU daily of vitamin D3.
6. Leventis P1, Kiely PD. London 2009 in Scand J Rheumatol. Good Tolerability and biochemical effects of high-dose bolus vitamin D2 and D3 supplementation in patients with vitamin D insufficiency in 69 RHEUMATOLOGY patients with vitamin D insufficiency [25-hydroxyvitamin D (25(OH)D) <40 nmol/L] 50 patients study 1 received 300 000 IU i.m. vitamin D2 (ergocalciferol), 19 patients in study 2 received 300 000 IU oral vitamin D3 (cholecalciferol) . Bolus i.m. vitamin D2 or oral vitamin D3 was well tolerated. change from baseline in serum 25(OH)D was significantly greater at 6 and 12 weeks in study 2 (p<0.0001 ). In study 1, a modest increase in mean serum 25(OH)D at 6, 12, and 24 weeks was observed but no patients achieved a serum 25(OH)D concentration > or = 50 nmol/L. PTH remained elevated in 42% of patients with secondary hyperparathyroidism at 12 weeks. In study 2, 100% and 89% of patients had serum 25(OH)D>50 nmol/L at 6 and 12 weeks, respectively. All patients with elevated baseline PTH were fully suppressed at 12 weeks. No hypercalcaemia was observed in either group. The 300 000-IU bolus of vitamin D2 or D3 was practical, well tolerated, and safe. Vitamin D3 had greater potency than equimolar vitamin D2, with a higher, sustained serum 25(OH)D response and efficacious PTH suppression.
7. Sempos CT1, Picciano MF ea . USA J Clin Endocrinol Metab. 2013 Jul;98(7):3001-9.. Is there a reverse J-shaped association between 25-hydroxyvitamin D and all-cause mortality? Results from the U.S. nationally representative NHANES. A reverse J-shaped association between serum 25-hydroxyvitamin D (25[OH]D) concentration and all-cause mortality was suggested in a 9-year follow-up (1991-2000) analysis of the Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994). We repeated the analyses with 6 years additional follow-up in 15 099 participants aged ≥ 20 years with 3784 deaths, to evaluate whether the association persists through 15 years of follow-up. The reverse J-shaped association became stronger with longer follow-up and was not affected by excluding deaths within the first 3 years of follow-up. Similar results were found from both statistical approaches for levels <20 through 119 nmol/L. Adjusted RR (95% confidence interval [CI]) estimates for all levels <60 nmol/L were significantly >1 compared with the reference group. The nadir of risk was 81 nmol/L 32pg/mL (95% CI, 73-90 nmol/L 29-36pg/ml). The association appeared in men, women, adults ages 20 to 64 years, and non-Hispanic whites but was weaker in older adults. A reverse J-shaped association between serum 25(OH)D and all-cause mortality appears to be real. It is uncertain whether the association is causal.
8. Logan Houghton ea Br J Nutr. New Zealand 2013;109:1082-8. Long-term vitamin D3 supplementation is more effective than vitamin D2 in maintaining serum 25-hydroxyvitamin D status over the winter months. Public health recommendations dont distinguish between vitamin D2 and vitamin D3, yet disagreement exists on whether these two forms should be considered equivalent. over the winter in healthy adults living in Dunedin, New Zealand (latitude 46°S), Participants aged 18-50 years were randomized to 1000 IU vitamin D3 (n 32), 1000 IUvitamin D2 (n 31) or placebo (n 32) daily for 25 weeks beginning at the end of summer. After 25 weeks, participants randomised to D2 and placebo had a significant reduction in serum 25(OH)D3 concentrations over the winter months compared with vitamin D3-supplemented participants (both P< 0.001). Supplementation with vitamin D2 increased serum 25(OH)D2 but produced a 9 (95 % CI 1, 17) nmol/l greater decline in the 25(OH)D3 metabolite compared with placebo (P< 0.036). Overall, total serum 25(OH)D concentrations were 21 (95 % CI 14, 30) nmol/l lower in participants receiving vitamin D2 compared with those receiving D3 (P< 0.001), among whom total serum 25(OH)D concentrations remained unchanged. No intervention-related changes in PTH were observed. Daily supplementation of vitamin D3 was more effective than D2;
9 Seijo M1, Oliveri B. ea Spain Medicina (B Aires). 2012;72:195-200. [Is daily supplementation with vitamin D2 equivalent to daily supplementation with vitamin D3 in the elderly?]. equivalence of cholecalciferol (D3) and ergocalciferol (D2) as well as their corresponding doses and administration route remain controversial to date. Twenty-one ambulatory postmenopausal women from Buenos Aires with a mean age of 77 ± 6.8 years were randomly assigned to one of the following groups: GD2 (n = 13): 800 IU (drops) and GD3 (n = 8): 800 IU (pills). Nineteen out of twenty one women showed deficient levels of 25OHD at baseline (< 20 ng/ml): GD2: 14.0 ± 4.8 ng/ml and GD3: 13.2 ± 4.9 ng/ml (NS). Whereas only GD3 exhibited an increase (≈ 25%) at 7 days, both groups showed a significant increase at the end of the study. However, neither attained adequate 25OHD levels (GD2: 17.4 ± 5.5 vs. GD3:22.9 ± 4.6 ng/ml; p < 0.001). Administration of 800 IU of vitamin D3 during 45 days was more effective than D2 in increasing 25OHD, but both failed to achieve adequate levels of 25OHD (= 30 ng/ml). but neither succeeded in achieving adequate levels of 25OHD (= 30 ng/ml).
10 Holick Tannenbaum ea usa J Clin Endocrinol Metab. 2008;93:677-81. Epub 2007 Dec 18.IN LOW DOSE eg 1000iu/d,
Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D A 1000 IU dose of vitamin D2 daily was as effective as 1000 IU vitamin D3 in maintaining serum 25-hydroxyvitamin D levels and did not negatively influence serum 25-hydroxyvitamin D3 levels. Therefore, vitamin D2 is equally as effective as vitamin D3 in maintaining 25-hydroxyvitamin D status.
11 Armas , Heaney ea.Creighton Univ Nebraska. J Clin Endocrinol Metab. 2004 ;89:5387-91.
Vitamin D2 is much less effective than vitamin D3 in humans.Vitamins D(2) and D(3) are generally considered equivalent in humans. Nevertheless, physicians commonly report equivocal responses to seemingly large doses of the only high-dose calciferol (vitamin D(2)) available in the U.S. market. Relative potencies of vitamins D(2) and D(3) were evaluated by administering single doses of 50,000 IU of the respective calciferols to 20 healthy male volunteers, following the serum vitamin D over 28 d.. The two calciferols produced similar rises in serum concentration, indicating equivalent absorption. Both produced similar initial rises in serum 25OHD over the first 3 d, but 25OHD continued to rise in the D(3)-treated subjects, peaking at 14 d, whereas serum 25OHD fell rapidly in the D(2)-treated subjects and was not different from baseline at 14 d. Area under the curve (AUC) to d 28 was 60 ng.d/ml for vitamin D(2) and 204 for vitamin D(3) (P < 0.002). Calculated AUC(infinity) indicated an even greater differential, with the relative potencies for D(3):D(2) being 9.5:1. Vitamin D(2) potency is less than one third that of vitamin D(3). Physicians resorting to use of vitamin D(2) should beware of its markedly lower potency and shorter duration of action relative to vitamin D(3)
12 Trang, Vieth ea University of Toronto, Am J Clin Nutr. 1998 . Evidence that vitamin D3 increases serum 25-hydroxyvitamin D more efficiently than does vitamin D2. In all species tested, except humans, biological differences between vitamins D2 and D3 are accepted as fact. Subjects took 260 nmol (approximately 4000 IU) vitamin D2 (n=17) or vitamin D3 (n=55) daily for 14 d. With vitamin D3, mean (+/-SD) serum 25(OH)D increased from 41+/-18 nmol/L before to 65+/-17 nmol/L after treatment. With vitamin D2, the 25(OH)D concentration went from 434+/-18 nmol/L before to 57+/-13 nmol/L after. The increase in 25(OH)D with vitamin D3 was 23+/-16 nmol/L, or 1.7 times the increase obtained with vitamin D2 (14+/-11 nmol/L; P=0.03). There was an inverse relation between the increase in 25(OH)D and the initial 25(OH)D concentration. In the highest tertile [25(OH)D >49 nmol/L] the mean increase in 25(OH)D was 13.3 nmol/L (P < 0.03 for comparison with each lower tertile). Although the 1.7-times greater efficacy for vitamin D3 shown here may seem small, it is more than what others have shown for 25(OH)D increases when comparing 2-fold differences in vitamin D3 dose. The assumption that vitamins D2 and D3 have equal nutritional value is probably wrong and should be reconsidered.
13. Hymøller L1, Jensen SK.Denmark J Dairy Sci. 2011;94:3462-6. Vitamin D₂ impairs utilization of vitamin D₃ in high-yielding dairy cows in a cross-over supplementation regimen. D(3) given after D(2) is less efficient at increasing the plasma status of 25(OH)D(3) than D(3) given without previous D(2) administration.
A Vitamin D Expert’s Take on the Latest Warning to Stay Out of the Sun to Avoid Skin Cancer
By Dr. Mercola 16/11/2014 The US Surgeon General recently came out with a warning on skin cancer,1 claiming that the sun is dangerous and that you need to stay away out of it.
pioneer Dr. John Cannell, founder of the Vitamin D Council, has dedicated a large part of his professional career to the study of vitamin D and its health benefits, and he has a warning of his own to those who take this narrow-minded advice to heart.
It’s worth noting that the acting Surgeon General, Boris Lushniak, is a dermatologist. And of all the medical specialties out there, dermatologists are clearly the most biased against sun exposure, & as a result, against vitamin D.
This isn’t surprising, since they primarily see the ill effects of sun overexposure. But in taking an overly narrow view, the advice to avoid sun exposure as much as possible can have equally if not greater adverse health effects. The Connection Between Sun Exposure and Skin Cancer Unquestionably, UV radiation can be dangerous; it can increase your risk for certain skin cancers such as squamous cell, basal cell, and melanoma. But there are significant differences even between these cancers, and appropriate sun exposure may actually be more beneficial than detrimental in some cases. Dr. Cannell explains:
“Squamous cell carcinoma is clearly associated with chronic sun exposure. It is more common on the face, the hands, and the scalp.
It is related to radiation burden over your lifetime, and together with basal cell carcinoma, which is sort of intermediate, it accounts for approximately 1,500 deaths a year in the United States…
Basal cell is sort of intermediate. There are studies showing that it is associated with chronic sun exposure, and there are studies showing that it’s not associated with chronic sun exposure.
And then there’s melanoma, which is responsible for almost 9,000 deaths a year and is the deadly skin cancer that is feared. The relationship that melanoma has with the sun is quite complicated.
It is clearly associated with sunburn, especially sunburns when you’re young (that’s incontrovertible) or sunburns in a sun tanning bed.”
However, there are at least two studies showing that melanoma is more common in indoor workers than outdoor workers. And the most likely places for melanoma to appear are actually NOT the face and the hands like squamous cell carcinoma, but rather the lower back and the upper leg—areas that are usually not chronically sun-exposed.
According to Dr. Cannell, there’s a vocal minority in the dermatological community that thinks the emphasis dermatologists have on avoiding sun exposure is wrong, because while sunburn is a risk factor, chronic sun exposure is not.
“A number of studies show that chronic sun exposure is related to melanoma, but they don’t separate out the sunburns, which is very hard to do because you have to do that by memory,” Dr. Cannell says. Two Decades-Long Study Finds Sun Avoidance Doubles Risk of Death Dr. Cannell notes a recent study2 done in Sweden, which followed nearly 30,000 middle-aged to older women for up to 20 years. The average follow-up was 15 years.
At the outset, they asked a number of questions about sun exposure, such as: Do you sunbathe? Do you take vacations in sunny areas in the winter? Do you garden with short sleeves and shorts? And, do you use sunbeds?
What they found, and this appears to be the only study of this kind, is that the women who avoided the sun were twice as likely to die over the course of the study. The researchers attributed this finding to a vitamin D mechanism.
What this study actually shows is that chronic sun exposure appears to be associated with less mortality. It’s also the first study to show that women who use tanning beds live longer than those who don’t.
This is in direct conflict to what almost every dermatologist will say, including the Surgeon General. It’s unfortunate, but the danger of almost any specialist is that they don’t take the broader perspective.
What the Surgeon General and almost every other dermatologist fail to take into account is the overall mortality, which is referenced in this recent study. Risk-Benefit Analysis In addition to this study, dozens of others document the benefits of appropriate sun exposure. This includes a reduced risk of about 16 different cancers of Dr. Garland’s studies suggest this reduction is close to 50 percent.
So many hundreds of thousands of people are put at risk from other cancers as opposed to 10,000 people who are dying from skin cancer caused by sunburn. It’s really a matter of making an educated risk-benefit analysis.
“When you do a risk-benefit analysis and you look at all the data we have, the risk in my opinion appears to be in those who avoid the sun,” Dr. Cannell says.
“Now, if you avoid the sun, your risk for non-melanoma skin cancer goes down. That’s clear. But if you look at studies of either latitude or of 25-hydroxyvitamin D levels in relation to cancer, you find this inverse relationship: the higher the vitamin D level, the lower the internal cancer rate.”
Dr. William Grant of Sunlight, Nutrition, and Health Research Center (SUNARC) estimates that if everyone in the United States had a vitamin D level of 40 nanograms per milliliter (ng/ml), it would save approximately 150,000 lives a year.3
That’s 100 times the rate of squamous cell cancers, which are the only ones that are definitively linked to UV exposure. In Canada alone, it is estimated that 37,000 lives a year are lost due to vitamin D deficiency.4 Also, use of sunscreen has risen in the last 30 years, so if dermatologists were correct, there should be a decrease in stage 1 melanoma. But there’s not. As sunscreen use increased, stage 1 melanoma diagnosis increased…
“It’s thought that by blocking out UVB, patients are able to stay out in the sun longer than they would have otherwise and expose themselves to the more dangerous, or at least potentially dangerous, UVA radiation that’s in the sunshine,” Dr. Cannell says. “What we recommend is what’s called safe, sensible sun exposures. The Australian Cancer Council now recommends the same thing. I think in England there’s now a change in their recommendation from strict sun avoidance to some safe, sensible sun exposure. There are some movements in large organizations to realize that safe, sensible sun exposure is a healthy thing.”
How Much Sun Exposure Is Sensible? On its website, Cancer Research UK reports that “by enjoying the sun safely and avoiding sunburn, people can reduce their risk of skin cancer and enjoy the beneficial effects of the sun.” Cancer Research UK’s sun advice is endorsed by the British Association of Dermatologists, Cancer Research UK, Diabetes UK, the Multiple Sclerosis Society, the National Heart Forum, the National Osteoporosis Society, and the Primary Care Dermatology Society. The UK National Health Service5 also recommends sensible, individualized sun exposure to help optimize vitamin D.
It’s important to recognize is how quickly sunlight can make vitamin D in the skin. You don’t need to be outside for hours on end. But you do need more than just a few minutes of sun on your face and arms. According to Dr. Cannell, sunbathing at solar noon in the summer, at most latitudes in the United States you will make between 5,000-10,000 international units (IUs) of vitamin D within 30 minutes.
“You can ask yourself why nature would evolve a mechanism that made so much vitamin D so quickly,” Dr. Cannell says. “When I thought about that question, the only answer I could come up with is nature did it for a good reason. The organism needs vitamin D, so the system in the skin evolved to make it very quickly upon exposure to sunlight.
We recommend full-body sun exposure for up to anywhere from a few minutes to 30 minutes every day. On those days when you cannot get a full-body sun exposure, we recommend a vitamin D supplement or sensible exposure in a low-pressure UVB bed.”
If you’re getting regular sun exposure, I think the need for an oral supplement is really minimal to non-existent. When you swallow a pill, there’s no self-regulating ability. Your body doesn’t have an ability to selectively limit its absorption. But your skin has the ability to control how much vitamin D is being produced based on how much is in your blood.
I personally have not taken oral vitamin D for five years and my level runs from 50-70 g/ml. Lifeguards, roofers, and gardeners who work with their shirt off, all tend to have levels between 40 and 80 ng/ml in the summer. This also brings up an interesting question about the difference between normal and natural. Normal vitamin D levels are an average of what indoor workers have in both winter and summer. Natural are levels of a population with widespread sun exposure. The latter is going to be closer to ideal, or optimal.
References for establishment of optimal levelsThere are also other reasons to strive for sun exposure rather than swallowing a pill. As noted by Dr. Cannell, aside from producing vitamin D, sunlight also affects nitric acid levels and endorphins in the skin. Researchers at the University of Wisconsin recently discovered that there may be a system at 311 nanometers that is separate from the vitamin D system (which is at 298 nanometers), and that there may be an entirely new undiscovered biochemical system in the skin that makes yet another substance, besides vitamin D. Time will tell what comes out of that research, but there are indications that sunlight may be responsible for other biological processes that are unrelated to vitamin D production.
Dr. Cannell’s Recommendation on Tanning Beds There are basically two
types of tanning beds:
- 1. High-pressure UVA beds. They tan you the quickest because it’s UVA that tans the skin. They contain only a limited UVB spectrum, and will therefore give you color but not much vitamin D
- Low-pressure beds, which contain less UVB than sunlight at most latitudes, but still contain a significant amount of UVB. These are the beds Dr. Cannell recommends, provided you’re using a sensible approach that avoids sunburns. It’s important to realize that you can easily get burned after only a couple or a few minutes when using a tanning bed
Another important factor when selecting a tanning bed is the type of ballast it employs, to avoid excessive electromagnetic field (EMF) exposure. Most tanning units use magnetic ballasts to generate light. These magnetic ballasts are well known sources of EMF fields that can contribute to cancer. If you hear a loud buzzing noise while in a tanning bed, it has a magnetic ballast system. I strongly recommend you avoid magnetic ballast beds, and restrict your use of tanning beds to those that use electronic ballasts.
On days you cannot get either regular sun exposure or use of a tanning bed, Dr. Cannell suggests taking 5,000 IUs of vitamin D3. Other vitamin D experts recommend similar amounts. It’s worth noting that, according to the federal government’s Food and Nutrition Board (FNB), the no observed adverse effects level (NOAEL) of vitamin D is 10,000 IUs a day. This means there has never been a replicated reliable study showing that 10,000 units a day is in any way detrimental.
Many individuals who have reported side effects from taking high doses of oral vitamin D have noticed that when they supplemented with magnesium, they were able to tolerate the high oral doses of vitamin D. Dr. Carolyn Dean has written in her book, The Magnesium Miracle, that she has seen this so many times that she doesn’t advise taking more than 2,000 units of vitamin D without magnesium supplementation. Be sure to also have an adequate amount of vitamin K2 along with D to slow the progression of arterial calcification. Remember though that the best form of vitamin D is the one your body produces when it is exposed to sunlight that has sufficient amounts of UVB.
Five Tips to Get an Appropriate, Sensible Amount of Sun Again, sunshine offers substantial health benefits, including vitamin D production, but you do need to exercise a few simple precautions to protect yourself from overexposure. Virtually all of the harm from sun exposure is related to sunburn. Here are my top five tanning tips: * Expose large amounts of your skin (at least 40 percent of your body) to sunlight for short periods daily. Optimizing your vitamin D levels may reduce your risk of as many as 16 different types of cancer, including pancreatic, lung, ovarian, breast, prostate, and skin cancers. If using a sunscreen, give your body a chance to produce vitamin D before you apply it. *When you’ll be in the sun for longer periods, cover up with clothing, a hat, or shade (either natural or shade you create using an umbrella). *Consider the use of an “internal sunscreen” like astaxanthin to gain additional sun protection. Astaxanthin is a potent antioxidant (and pigment) produced by marine algae in response to their exposure to UV light. Typically, it takes several weeks of daily supplementation to saturate your body’s tissues enough to provide protection. *Consuming a healthy diet full of natural antioxidants is another useful strategy to help avoid sun damage. Fresh, raw, unprocessed vegetables and fruits deliver the nutrients that your body needs to maintain a healthy balance of omega-6 and omega-3 oils in your skin, which is your first line of defense against sunburn. Vegetables also provide your body with an abundance of powerful antioxidants that will help you fight the free radicals caused by sun damage that can lead to burns and cancer.
How Vitamin D Performance Testing Can Help Optimize Your Health A robust and growing body of research clearly shows that vitamin D is absolutely critical for good health and disease prevention. Vitamin D affects your DNA through vitamin D receptors (VDRs), which bind to specific locations of the human genome. Scientists have identified nearly 3,000 genes that are influenced by vitamin D levels, and vitamin D receptors have been found throughout the human body.
14 Oct 2014 update: MORE ON OPTIMAL VITAMIN D3 DOSE, AND THE DIFFICULTY OF ACHIEVING CLINICAL OVERDOSE: Four new reports highlight how difficult, and important it is to achieve adequate optimal bloodlevels of vitamin D with vigorous vitamin D3 supplements, let alone overdose with any significant adversity: note three used the recommended vitamin D3, not the long-condemned mislabeled Lennons/Aspen vitamin D2 (which is misleadingly labelled “caciferol” without disclosing that it is D2 not D3). Even a single 2 million iu overdose of vit D3 in nonagenarians had no adverse effect-since the bloodlevel was back to zero by 3 weeks, thats above 100 000iu/day on average….
with serum 25-hydroxy vitamin D (25(OH)D) < 30 ng/mL on placebo or vitD3 (n = 35) 60,000 units/week for 6 weeks. mean baseline level of 25(OH)D was 9.6+-9.6 ng/mL, and after 6 weeks doubled to 19.5 ± 4.3 ng/mL, (P < 0.0001). After discontinuing supplement at 6 weeks, serum 25(OH)D level dropped moderately by 12 weeks (16.1 ± 8.3 ng/mL) as compared with the baseline. The change in serum 25(OH)D level from baseline to 6 weeks in the intervention group was inversely related to baseline 25(OH)D levels and patient’s weight. In the control group, change in 25(OH)D was not significant. Thus vit D3 about
10 0000iu/day in these small and often malnourished people raises bloodlevel by only about 10ng/mL.
van den Ouweland , Vollaard ea Nijmegen, The Netherlands in BMC Pharmacol Toxicol. 2014 Sep 30 describe Pharmacokinetics and safety issues of an accidental oral overdose of 2,000,000 IU of vitamin D3 in two nonagenarian nursing home patients: a case report. Oral overdose of 2,000,000 IU of vitamin D3 in two nonnagenarian nursing home patients was monitored from 1 hr up to 3 months . Peak blood 25(OH)D3 concentrations were observed 8 days after intake (210 and 162ng/mL, respectively (ref: 20-80 ng/mL), followed by a rapid decrease to undetectable levels after day 14. Remarkably, plasma calcium levels increased only slightly up to 2.68 and 2.73 mmol/L, respectively (ref: 2.20-2.65 mmol/L) between 1 and 14 days after intake,; phosphate and creatinine levels remained within reference range. No adverse clinical symptoms were noted. CONCLUSION:A single massive oral dose of 2,000,000 IU of vitamin D3 does not cause clinical toxicity requiring hospitalization. Toxicity in the long term cannot be excluded as annual doses of 500,000 IU of vitamin D3 for several years have shown an increase in the risk of fractures. This means that plasma calcium levels may not be a sensitive measure of vitamin D toxicity in the long term in the case of a single high overdose.
As previously reported, to avoid dehydration stones and vascular calcification – especially in hot dry climates – , the precautions with vigorous vit D3 are to add some vit K2 and magnesium to the supplement, and maintain good water intake .
The fourth current paper, from Morocco, reports inexplicable use of dangerous massive dose of vit D2 in neonates- amounting to about 120 000iu/kg
ie about 12 times the maximum adult dose reported :
Hmami , Bouharrou ea Morocco University,
Arch Pediatr. 2014 Oct;21:1115-9.
[Overdose or hypersensitivity to vitamin D Vitamin D intoxication with severe hypercalcemia is rare in the neonatal and infancy period. 9 babies between ages of 25 and 105 days were admitted for treatment of severe dehydration 8 to 15% with hypercalcemia, with preserved diuresis and loss weight between 100 and 1100 gm secondary to taking 600,000 units of vitamin D (Sterogyl(®). The pregnancies & deliveries were normal. Clinical signs were dominated by weight loss, vomiting, and fever. The vitamin D values in nine patients were toxic (mean 220: 139 – 300 ng/mL, ; normal >20ng/mL; toxicity if >100ng/mL). Nephrocalcinosis was shown in seven patients. DNA study in eight patients, did not reveal a mutation of the vitamin D 24-hydroxylase gene (CYP24A1). Treatment consisted of intravenous rehydration with diuretics and corticosteroids. Serum calcium returned to normal range within 4-50 days, with weight gain progressively over the following weeks. The follow-up (2 years for the oldest case) showed persistence of nephrocalcinosis. Genetic susceptibility and metabolic differences appear to modulate the threshold of vitamin D toxicity. However, respect for recommended doses, recognized as safe in a large study population, reduces the risk of toxicity.
VITAMIN D3 DOSE: We get excellent results in outpatient adults with loading oral dose of vit D3 of about 200 000 to 400 000iu depending on illness severity and body mass; then pro rata about 50 000iu per week till better, tapering to fortnightly when well; pro rata in kids. We monitor calcium and 25OH vitamin D3 levels occasionally if affordable – but with the tapering regime, and published data, do not see or expect hypercalcemic problems from a mean conservative weekly maintenance dose of about 3500iu/d longterm, with predicted bloodlevel of 25OHvitD of about 35-40ng/ml. As a senior with average chronic dis-ease load, I take ~63 000iu vit D3 weekly, but double it occasionally if I do get a bad cold; so I never miss a day’s work; recent stress-related shingles (2nd attack in 30 years) was just a nuisance, settled in 3 weeks with this regime plus multigrams of buffered vit C a day; oral lysine and alphalipoic acid each about 1/2 gm/day; and for a few days some weak steroid and humic acid cream topically for the neuritis and blistering, which has already healed to almost invisible. This week at a family practice clinic I saw two successive women with shingles – now a frequent occurrence, even without HIV…
Khan in Toronto in OHDM this September describes a ~60yr old man with tongue cancer who was treated inter alia with Vit D3 10 000iu a day; after a year his 25oH vitD level was ~106ng/ml, when his dose was halved; his dose response bore out the general experience that at average adult mass, vit D level rises by about 10ng/ml for every 1000iu vit D3 per day or pro rata dose weekly etc eg 50 000iu/wk or 100 000iu fortnightly may give average vit D level of ~70ng/ml. .
Singh & Bonham 2014 at Kansas University describe A Predictive Equation to Guide Vitamin D Replacement Dose in Patients. “The recommended daily allowance for vitamin D is grossly inadequate for correcting low serum concentrations of 25-hydroxyvitamin D in many adult patients. In their population (average BMI 31.5) ,about 5000 IU vitamin D3/day is usually needed to correct deficiency, and the maintenance dose should be ≥2000 IU/day. The required dose may be calculated from the predictive equations specific for ambulatory and nursing home patients” A BMI of 31.5kg at a mean height of about 1.7m gives a mean weight of 91kg, which at the consensus daily vit D3 dose of 80iu/kg/d totals ~7100iu/d or 50 000iu/wk- perhaps a reasonable maintenance dose for winter, half that in summer if reasonable weekly sun exposure. .
29 Sept 2014: As detailed elsewhere in this column, there is at least 70 years of strong experience worldwide that all microorganism infections are greatly diminished by natural prevention (not synthetic vaccines loaded with toxic heavy metals and allergenics eg egg) , and easily treated ie thrown off, with vigorous immune-boosting supplements: (mega)grams a day of vitamin C or as kgs/day of fresh produce; vitamin D3 80+ iu/kg/d to >10 000iu/d ie 300 000 to 600 000iu loading dose; then +-50 000iu/wk, plus plenty of skin exposure to sunshine; iodine; zinc; selenium; silver; the other vitamins; Ecchinacea etc. This applies both to acute and chronic infections and degenerative conditions.
To be used in highrisk cases eg MERS, AIDS, ebola etc: The landmark trial Effect of High-Dose Vitamin D3 on Hospital Length of Stay in Critically Ill Patients With Vitamin D Deficiency– The VITdAL-ICU Randomized Clinical Trial by Amrein, Dobnig ea , published today in JAMA from Austrian hospitals is most encouraging about the immense value of vigorous dose and bloodlevels of vitamin D3 against all types of severe disease. The dose used in this trial (loading dose 540 000iu =~18000iu/d 1st month, but averaging only ~8000iu/d in the first 3mo) did not achieve vigorous vit D bloodlevel, presumably because the loading dose of vit D3 in oil (540 000iu) was given by tube into the stomachs of critically ill patients; it would have better been given by transdermal injection, or else a much higher loading gastric dose given so as to speedily achieve a bloodlevel of around 70 (60 to 80) instead of half of this that was achieved in the crucial first few weeks . “ from May 2010 through September 2012 at 5 ICUs the trial recruited 492 medical (60%) and surgical (40%) critically ill adult white patients , 35% women, BMI mean 27, mean age 64.6 years (SD, 14.7) with vitamin D deficiency (≤20 ng/mL) assigned to receive either vitamin D3 540 000 IU, or placebo given orally or via nasogastric tube; ; followed by monthly maintenance doses of 90 000 IU for 5 months- ie= about 18000iu/day for the first mo, then 90 000iu mthly ie only 3000iu/d. . RESULT: on placebo the 25hydroxyvit D3 level doubled from 13 at baseline to 17 at a month to 26ng/ml at 6mo.. By contrast, on vit D3 supplement it doubled to 34 at days 3 and 7 and day 28, but up to 46 at 6 months ie only 80% higher than the control group – thus 1/3 to 1/2 of the optimal target; with this, where 100% of patients were below 25OHvitD at baseline ie on admission to ICU, by 7 days, 87% were still in this bracket and none above 60ng/ml on placebo vs 25% below 20 and 13% above 60 on vit D3; and by 6mo 35% were still that low on placebo, vs 5% at that low, but 22% above 60 on vit D3. So it is not surprising that Median hospital stay 20 days was not significantly different between groups Hospital mortality and 6-month mortality were also not significantly different (hospital mortality: 28% for vitamin D3 vs 35% for placebo; hazard ratio [HR], 0.81 P = .18; 6-month mortality: 35.0% for vitamin D3 vs 42.9% for placebo; HR 0.78 P = .09). For the severe vitamin D deficiency subgroup analysis (n = 200), length of hospital stay was not significantly different between the 2 study groups: 19.5 days. Hospital mortality was significantly 40% lower with 28 deaths among 98 patients (28.6% ) for vitamin D3 compared with 47 deaths among 102 patients (46.1% ) for placebo (HR, 0.56 P for interaction = .04), but not 6-month mortality (34.7%] for vitamin D3 vs 50.0% for placebo- ie 31% lower; HR, 0.60, P for interaction = .12). No serious adverse events were observed. The highest 25-hydroxyvitamin D levels measured were 107 ng/mL on day 7 and 106 ng/mL at month 6- well below the theoretical minimum toxic threshold of 150 or 250ng/ml..”
BUT compared to the Austrian trial in overweight 27+kg BMI elderly whites given 540 000iu to start by tube, in Salahudfin ea’s randomized controlled trial in young emaciated Pakistani men BMI 17.2kg, Vitamin D3 600 000iu injection (which achieved twice the blood 25OH vit D3 level of the Austrian patients), had accelerated clinical recovery from tuberculosis with “impressive clinical (weight gain, chest xray and sputum clearing) improvement over 3 months on outpatient TB therapy (Directly Observed Therapy (DOTS) with 2
months of 4 antituberculous drugs followed by 6months Isoniazid and Ethambutol) with two doses 600 000iu vit D3 imi (vs placebo inj) a month apart- ie = ~20 000iu/d for the first 2 months, but equivalent to about 7 000iu/day over the 3 months treatment period . This dose of vitamin D is as recommended for vitamin D supplement by the Pakistan Endocrine Society. Trough 25OH vit D levels increased from about 20 to 90ng/ml. After 12weeks, the vitamin D supplemented pts (mean 28 yrs, BMI 17.2kg, 85% moderate to far advanced lung disease) had significantly greater mean weight gain (kg)+3.75, versus+2.61, p 0.009; lesser residual disease by chest xray- 30% fewer zones involved 1.35 v/s 1.82 p 0.004, and 50% or greater reduction in cavity size 106 (89.8%) v/s 111 (94.8%), p 0.035. Vitamin D supplementation led to significant increase in MTBs-induced IFN-g secretion in patients with baseline ‘Deficient’ vitamin D serum levels (p 0.021). Patients in the vitamin D arm and serum < 30 ng/mL (‘Insufficient’ and ‘Deficient’ groups) at enrollment had significantly greater improvements in TB severity scores compared to patients with normal baseline vitamin D levels; p 0.014.”
“This corresponds with the earliest reports of the benefits of vitamin D in TB patients published in 1848 [21] that describes disease arrest, weight gain and reduction in mortality in patients with TB treated with cod liver oil compared to standard therapy alone. More recently, Martineau et al [7] demonstrated that a single oral dose of 2.5mg (100,000IU) of vit D2 significantly reduced growth of mycobacteria . A randomized, placebo controlled study on 67 Indonesian patients, by Nursyam et al , Jakarta [22] reported that pulmonary TB patients given 420,000IU of vitamin D over 6weeks ie 10 000iu/day had significantly higher sputum conversion rates as compared to placebo (p 0.002). Martineau et al. [8] showed that 100,000 IUs of 25-hydroxyvitamin D3 supplementation significantly improved sputum conversion rates in patients with the Taq1 25-hydroxyvitamin D receptor polymorphism of the tt genotype. ” .
As Salahuddin ea note, the good results in Pakistan in only 3 months with vigorous INITIAL dose vit D3 contrasts with Two recently published large randomised, controlled trials of conservative vitamin D3 over months that achieved far lower blood vitamin D levels found no difference in clinical outcomes or mortality after 400,000IU of 25-hydroxyvitamin D3 or placebo were given by Martineau ea in London, UK to 146 pulmonary TB patients – where mean (trough or midpoint) vit D level (after 100 000iu vitamin D(3) or placebo at baseline and 14, 28, and 42 days after starting standard tuberculosis treatment) – was surprisingly only 40ng/ml at 56days – ie after a mean of 7000iu/d by 56 days, vs 10ng/ml on placebo)- less than half of the bloodlevel achieved on vit D3 in the Pakistan trial.
So the Austrian ICU patients would undoubtedly have done much better if given more effective (ie in critically ill pts intramuscularly imi or subcutaneously) loading dose like the Salhuddin trial did.
TIME To SWOP FROM MISNAMED “STRONG CALCIFEROL” VIT D2 TO THE REAL VIT D3: as the winter solstice approaches here, with fierce weather linking to the expected influenza-like outbreak (while the MERS-CoV outbreak abates with summer in the severely vitamin D deficient Saudi Arabians), a new major study shows the supremacy of vitamin D3 for supplementation, and confirms that vitamin D2 benefit if any is so mediocre as to be unethical..
Its sad that despite the strong evidence against using vitamin D2 supplement discussed last year, it seems no one acted on it despite the confirmatory paper from Bergen of last September.
Thus vit D3 is again confirmed as four times as potent as D2. But crucially, that giving vit D2 may actually SUPPRESS the optimal serum vit D3 level.
We health professionals with our highly vulnerable populations in South Africa and worldwide (epidemic/endemic HIV, TB, cancer, drug addiction, MERS-CoV, asthma, diabetes, cardiovascular, malnutrition, alcoholism and violence) therefore surely have no choice but to swop promptly from prescribing vit D2 “Strong Calciferol” (a dangerous misnomer) to prescribing vitamin D3 at vigorous dose (with if possible occasional blood level check of 25OHvit D3)- at a trivial imported and distributed cost (100cws) to South African state clinics of perhaps<1/4 of the cost of D2 eg R1 per patient per month for a conservative 100 000iu monthly (ie after an appropriate germicidal loading dose of eg 3000 iu/kg) if not the more realistic dose double that- still at only eg US$0.2 a month.
Health Authorities everywhere have an obligation to enforce the use of vitamin D3 and not vitamin D2 globally ..
update 3 Sept 2014: while the MERS outbreak in Arabia may at last be dying down, real highly infections plagues eg ebola malaria cholera typhoid, MRSA, TB and HIV etc continue rampant, maiming and killing even more than the manmade wars raging on some continents. .
So it is ironic – or typical of the couldnt-care-less greedy politicians and potentates who run the world- that the medical authorities they employ worldwide apparently continue to ignore the dramatic benefits of at least safe antimicrobial supplements like multivite, zinc, iodine, selenium, and especially vigorous dose vitamin D3 at negligible cost, and highdose buffered vitamin C to tolerance, and colloidal silver.
Already 35 years ago Italian researchers published on Pubmed that vitamin D3 should be used orally rather than injected D or as oral vitamin D2: [Behavior of serum vit D in humans after administration of vitamin D. Boll Soc Ital Biol Sper. 1979 Coen G, Casciani CU ea. “evaluated Serum levels of 25 hydroxy-vit D following injected and oral vit. D2 and D3 . While no rise in 25OHD3 serum levels was observed after i. m. administration , a marked rise was found following the oral administration. However the peak values were largely impredictable.”
We quote above trials and evidence that oral vit D2 may be actually harmful, that it is vit D3 in vigorous dose that is needed to at least treble if not quadruple the blood vit D level from the usual deficient levels we find, to between 60 and 100ng/ml during illness. Unfortunately locally this is not only not grasped, but also the vit D assay kit being used by private laboratories measures only total 25OHvit D level, not the needed active 25OH vit D3 level plus the potentially harmful (vitD receptor-blocking ) 25OHvit D2. This is a crucial omission which has been corrected by eg the Mayo Clini Lab, which routinely reports both D3 and D2 levels.
In the person not on vit D supplements, the mediocre ie insufficient total vit D level may mask that the crucial vit D3 level is actually seriously low- deficient. In the person on vigorous vit D2 supplement (the spuriously named “strong calciferol” 50 000iu tab no longer prescribed in USA but commonly in RSA, that neglects to state it is D2 not D3), the total 25OH vit D assay will be even more misleading if the level is well up, without the unwary being informed that it is harmful D2 that is elevated, and blocking the needed vit D3 level that the D2 is suppressing.
15 June 2014 CRUCIAL EFFECTIVE VITAMIN D3 DOSING: A major new metaanalysis of the benefit of Vitamin D3 and Respiratory Tract Infections RTI in PLOS 2013 at Sweden’s Karolinska Institute Bergman ea showed that in the 11 relevant trials (published between 2007 and 2012 ie done through the first decade of this century) using vit D3, “Overall, vitamin D showed a protective effect against RTI (OR, 0.64; 95% CI, 0.49 to 0.84). And the average vit D level at baseline was only 24ng/ml, but with the mediocre vit D3 doses used then of average 2000iu/d (300 – 4000iu/day) given for between 7wks and 3 yrs, the average bloodlevel achieved on replacement was only 50% higher at 36ng/ml”.
This confirms more direct experience with higher doses that blood level increment, and benefit, is proportionate to vit D3 dose, at least up to the proven speculative safe upper dose of at least 10 000iu/day (whereas the proven safe longterm daily dose is up to 50 000iu/day). “More important, the protective effect was larger in studies using once-daily dosing compared to eg monthly bolus doses (OR
=0.51 vs OR=0.86, p=0.01)”. This concurs with our experience of major benefit against respiratory infection that is based on published studies giving a loading month’s dose of about 80-100 iu/kg/day ie ~3000iu/kg; then that monthly dose split conservatively eg 50 000iu every week or two depending on mass, and severity of ill-health; to a more successful blood-level of 60 to 100ng/ml.
Similarly, the 2014 VIDA trial across USA- Effect of Vitamin D3 on Asthma Treatment Failures in Adults With Symptomatic Asthma and Lower Vitamin D Level, Castro ea, showed “Vitamin D3 for 28 weeks did not reduce the rate of first treatment failure or exacerbation in adults with persistent asthma and vitamin D insufficiency. These findings do not support a strategy of therapeutic vitamin D3 supplementation in patients with symptomatic asthma”. But this trial had the same severe limitation as the Swedish metanalysis of vit D3 benefit- it also used only 4000iu/d. “While all were vitamin D insufficient ie below 30 ng/ ml before the trial and half were deficient with levels below 20 ng/mL, supplementation brought levels above the 30 ng/mL threshold for 82% in that group – mean levels were 41.8 ng/mL at week 28 in the supplement group, while the mean stayed in the deficient range for those who got placebo. ” So 4000iu/day merely doubled the bloodlevel to only about 40ng/ml – only about half of the putative optimal dose.
These recent studies force us to conclude that bad weather, and bad prevalent respiratory viruses, and especially with major acute, or chronic illness as in those with or at risk of serious infections eg major trauma or sepsis, MERS-CoV, Ebola, malaria, cholera, cancer, diabetics, smokers, asthmatics, bronchitics, AIDS-TB., pneumonia and old age sufferers, and especially hospital, laboratory and clinic- health workers- we should give a loading dose of about 4000iu/kg, then 10 000 iu/d for an average 70kg adult, or 50 000iu every 5 days, or more simply 75000iu (about 1.5ml of 100cws vit D3 powder) weekly; or at a stretch, 300000 if not 400 000iu monthly. . As the common imported powder concentrate is 100 000 iu / Gm ie per 2 ml, it is simple to take the slightly sweetish powder up to 2 or more 4 ml teaspoons ie 200 000 -400 000 iu on the tongue.
The majority of residents of developed countries now live urbanised with mechanized transport, do not live and work / walk all day stripped in the sun. The poor malnourished peasants live crowded in ghettoes , and the poorest are generally the darkest skinned and therefore make the least vitamin D3. So with rare exceptions, everyone needs the vigorous vitamin D 3 doses discussed above.
But at the prevalent bulk vit D3 powder price of at most about $0,o2 per 100 ooo iu, at a mean population age of around 20 to 25 yrs -outside Europe- it would cost a country of eg 50 million people perhaps $o.5 per head per year ie conservatively $25 million a year to prevent > 90% of common illnesses including drugging and violence consequences. Of course no government can tolerate such massive loss of jobs and taxes in a decimated disease industry that turns over $ trillions annually – up to 18 % of national budgets. So it’s up to individual adults, especially householders, educators and employees , to see that the cheapest cure- all after clean water – vitamin D3 – is recommended and freely available.
We health professionals with our highly vulnerable populations in South Africa and worldwide (epidemic/endemic HIV, TB, cancer, drug addiction, MERS-CoV, asthma, diabetes, cardiovascular, malnutrition, alcoholism and violence) therefore surely have no choice but to swop promptly from prescribing vit D2 “Strong Calciferol” (a dangerous misnomer) to prescribing vitamin D3 at vigorous dose (with if possible occasional blood level check of 25OHvit D3)- at a trivial imported and distributed cost (100cws) to South African state clinics of perhaps<1/4 of the cost of D2 eg R1 per patient per month for a conservative 100 000iu monthly (ie after an appropriate germicidal loading dose of eg 3000 iu/kg) if not the more realistic dose double that- still at only eg US$0.2 a month.
Health Authorities everywhere have an obligation to enforce the use of vitamin D3 and not vitamin D2 globally ..
2 February 2014 VITAMIN D 3 DENIALISM: Dr John Cannell psychiatrist and nutritionalist of the Vitamin D Council has posted a comprehensive rebuttal of the Autier review’s damnation of vitamin D at http://www.vitamindcouncil.org/blog/a-look-at-the-recent-lancet-review-study/.
Queries and rebuttals all over the world are questioning the negative French (Autier ea) Vitamin D status and ill health: a systematic review published last month by the UK Lancet Low serum concentrations of 25-hydroxyvitamin D (25[OH]D) have been associated with many non-skeletal disorders. However, whether low 25(OH)D is the cause or result of ill health is not known. We did a systematic search of prospective and intervention studies that assessed the effect of 25(OH)D concentrations on non-skeletal health outcomes in individuals aged 18 years or older. We identified 290 prospective cohort studies (279 on disease occurrence or mortality, and 11 on cancer characteristics or survival), and 172 randomised trials of major health outcomes and of physiological parameters related to disease risk or inflammatory status. Investigators of most prospective studies reported moderate to strong inverse associations between 25(OH)D concentrations and cardiovascular diseases, serum lipid concentrations, inflammation, glucose metabolism disorders, weight gain, infectious diseases, multiple sclerosis, mood disorders, declining cognitive function, impaired physical functioning, and all-cause mortality. High 25(OH)D concentrations were not associated with a lower risk of cancer, except colorectal cancer. Results from intervention studies did not show an effect of vitamin D supplementation on disease occurrence, including colorectal cancer. In 34 intervention studies including 2805 individuals with mean 25(OH)D concentration lower than 50 nmol/L at baseline supplementation with 50 μg per day or more did not show better results. Supplementation in elderly people (mainly women) with 20 μg vitamin D per day seemed to slightly reduce all-cause mortality. The discrepancy between observational and intervention studies suggests that low 25(OH)D is a marker of ill health. Inflammatory processes involved in disease occurrence and clinical course would reduce 25(OH)D, which would explain why low vitamin D status is reported in a wide range of disorders. In elderly people, restoration of vitamin D deficits due to ageing and lifestyle changes induced by ill health could explain why low-dose supplementation leads to slight gains in survival.
and the accompanying anonymous Lancet editorial: chasing a myth?
Ongoing randomised clinical trials assessing the ability of vitamin D supplementation to reduce the risk of several non-skeletal disorders involve a population larger than that of Cambridge, UK, and will cost millions of research dollars. VITAL, for example, will enroll 20 000 participants and has US$22 million in funding. This vast investment of effort by patients, researchers, and funders is laudable, as it is almost certain that it will be sufficient to answer a question that has long kept the medical community in the dark.
Vitamin D first became a medical success story when its importance in bone health and calcium homoeostasis was proven decades ago. Since then, epidemiological evidence has been accumulating to support a role for vitamin D in the protection of individuals from various non-skeletal disorders including cancer, cardiovascular diseases, autoimmune and inflammatory diseases, dementia, and diabetes; it might also reduce all- cause mortality. Many of these studies show a strong association between low vitamin D concentrations anddisease. However, the results of myriad recent small randomised controlled trials are almost unanimous in concluding that vitamin D supplementation provides protection from few, if any, of these outcomes.
Vitamin D is a steroid hormone with pleiotropic and tissue-specific effects owing to the wide expression of the nuclear vitamin D receptor in many different tissues,and the many genes that are targeted by its actions. In the skeletal system, vitamin D promotes healthy development and remodelling of bone. In other tissues, vitamin D is postulated to mediate potentially beneficial effects via a wide variety of mechanisms: some evidence suggests that it exerts anticancer activity by limiting hyperproliferation of certain cell types, that it promotes metabolic health by regulating lipid metabolism in adipocytes, and that it limits autoimmunity by suppressing inappropriate immune responses. In a systematic review in The Lancet Diabetes & Endocrinology editorial , Philippe Autier and colleagues discuss a large number of observational studies suggesting That high serum concentrations of vitamin D might be protective.
For example, those with high vitamin D had decreased risk of cardiovascular events by up to 58%), diabetes (by up to 38%), colorectal cancer (by up to 33%), and all-cause mortality (by up to 29%). However, they also compare these findings with the results of randomised clinical trials, which reveal a very different picture: no reduction in risk was found, even in trials involving adequate supplementation of participants with lowvitamin D levels at baseline (less than 50 nmol/L). Autier and colleagues also did a new meta-analysis of 16 trials that assessed the effects of vitamin D supplementation on blood HbA1c, a biomarker mainly used for monitoring disorders of glucose metabolism.
Although type 2 diabetes is associated with low vitamin D, the results show that vitamin D supplementation does not reduce HbA1c
. Thus, it looks increasingly likely that low vitamin D is not a cause but a consequence of ill health.
Despite the growing body of evidence indicating that vitamin D is unlikely to prevent non-skeletal disorders, there is strong support for its use from many prominent members of the research community, which is fuelled by the relatively low toxicity of vitamin D, the glimmer of positivity from some trials,and the large body of evidence from prospective observational studies. For those who ‘believe’, the lack of benefi t found in most trials completed thus far can be attributed to issues including inadequate supplementation, testing of a population not sufficiently vitamin D deficient at baseline, incorrect
formulation, underpowering, or insufficient follow-up. Vitamin D might not be safe in all settings, however.
Supplementing at high doses could cause harm in people with already high concentrations of serum vitamin D, particularly in those with liver, kidney, or vascular problems. This is a concern, given the large number of people taking vitamin D supplements (up to 50% of adults in the USA).
Large clinical trials to assess the effects of vitamin D on non-skeletal health outcomes are therefore justified. It would be a real boon to patients if the results are positive, but unless effect sizes for clinically important outcomes are large, the results will only confirm the neutral effect reported by most clinical trials thus far. Although this investment might therefore have little effect on current guidelines, the results will at least allow the research community to move on.
This French review of Vitamin D is the sort of tactic regularly concocted by Big Pharma and the Disease Industry for the media, to discourage patients and doctors from taking/prescribing effective doses of supplements (beyond a lowdose multivite a day), instead force them to take Big Pharma poisons- synthetic new risky designer drugs- like antibiotics, antipain, anticancer, anticholesterol, antiosteoporosis, antiplatelet,antihypertensive, vaccines, antiflu, – to make massive profits for the Disease Industry, but not address or cure the deficiency causes of disease. At the behest of Big Pharma like Roche, their lobbyists the FDA, the European Medicines Authority and the UK NHS are trying to push through legislation that will make anything but lowdose multisupplements available to the public solely on doctors’ prescription.
Meanwhile, Big Pharma companies are paying fines of over $10 billion a year for promoting their snakeoil prescription designer drugs by fraud, when these drugs are allowed to be registered for chronic use after small trials of only 6 to 12 weeks, and the researchers who publish the trials for megadollar fees are regularly caught out, fired but rarely jailed. …… The Big Pharma guys simply bill the cost of the fines into their marketing expenses- their bosses, and the politicians they buy off, are too big to jail… Regulators then allow the drugs to be prescribed for years until enough patients sicken and die for there to be an uproar and cancellation- as happened recently with Prot(e)os the synthetic ranelate ‘osteoporosis’ snakeoil;. Now a top Dutch researcher has been fired for falsifying trials to promote betablockers for hypertension – when these have been discredited as routine therapy for this purpose for over a decade.
yet the Regulators led by the FDA – which is massively funded solely by Big Pharma as their ally- insists that vitamins, minerals and other long-proven natural supplement therapeutics, prime human hormones like melatonin and physiological human sexhormone creams , have to undergo $multimillion trials before they can be marketed as already long-evident safe effective therapies.
none of the vit D trials used the dose of vit D3 now recommended on solid evidence that we should all take – 80 (to 100)iu/kg/day or 2400-3000iu/kg/month of vitamin D3- ie about 150 000 – 200 000 iu to start and then per month for average adults – to maintain healthy 25OH vit D levels around 60-100ng/m (here our bloodlevels are usually between 10 and 20 ! because we take little dairy products, nuts and sunshine- we cover up and live indoors.) .
Most of the reported trials used only about 5% of the recommended vit D dose ie ~200 to 400iu/day ie 6 iu/kg/day! this dose does nothing except partly prevent rickets- in infants! Pregnant women are still routinely given such weak near-nonsensical doses of vit D.
and as Cannell’s review of the Autier analysis points out, the vitamin D trials trials under way – * in USA-Boston VITAL study 20 000pts) , Finland (FIND 18000 pts and UK(VIDAL 1600pts ) , in some 40 000 subjects, due for publication only between 2017-2020- are using only 1600 to 3200iu vit D a day or about 48 000 to 96000iu/month ie perhaps 32iu (25 to 40) /kg/day. So they are testing still modest doses and blood level targets. .
Read about the fraud of the Disease Industry at https://healthspanlife.wordpress.com/2014/01/20/vitamins-c-d3-avoiding-vitamin-denialism/ – especially about the dodgy ” Strong Calciferol’ tabs (Lennons)- which are not what you expect (vit D3) but vit D2 (the label, and package insert, dont tell you this) . vit D3 powder is half the price but apparently 4 times as strong as D2.
ideally you should check your 25OH vit D and calcium levels to make sure you are on the right dose- but always taking some magnesia supplement, and at least 2 liter of water/ sodawater/clear fluid a day to avoid dehydration, kidney stones and vascular disease (which highdose calcium supplement eg 1000mg & vit D3 400iu/day cause).
8 April 2013 UPDATE: VITAMIN D3 THE AMAZING SUPPLEMENT
It is sad to record that Dr Walter Stumpf died suddenly a few months ago during ongoing correspondence. The world has lost a teacher of the century in both biological sciences and the humanities, metaphysics and philosophy,..
This week – as flu mushrooms in the southern hemisphere autumn- the Canadian Medical Association Journal April 3-8 features early-release articles on concerns about the Asian flu viruses and especially the SARS-nCorVirus. Is mass vaccination the answer? or did this in fact worsen mortality in previous North American epidemics of eg H1N1? which brings us back to global protection against infections and all major diseases with lowcost safe VitaminD3 at say 50 000iu(~700iu/kg)/week plus the other all-system protective supplements – eg multivitamins (especially vit C and K) and minerals especially magnesium, zinc, idine and selenium; and during epidemic times, major daily boost in vits D3 and C.
In December 2012 the University of San Diego published a useful researched update on vitamin D3 and breast cancer; pointing out again that while the increase in benefit obviously drops off with increasing dose, safe dose is up to at least 10 000iu a day or 70 000iu a week, to a bloodlevel around 100ng/ml; and toxic dose requires at least 40 000 iu a day chronically (if not 600 000iu/d as other evidence suggests). The projections for breast cancer reduction fit with the same team’s predictions in 2007.
So apart from maintaining good water intake, and avoiding taking ill-advised unbalanced solo calcium supplement, for optimal dosing in those with cancer or any other high risk, blood levels of both 25hydroxy vit D3, 1,25 calciferol, calcium, phosphate and creatinine, should be monitored occasionally, to avoid the rare risk of kidney stones and arterial/breast calcinosis.
Remember that magnesia, phosphate and vitamin C and K2 supplements are amongst the most important of at least 40 to accompany vitamin D3.
Last month three new studies affirmed the importance of vigorous vitamin D3 levels for genetic, heart and all health.
Holick’s group at
Boston University show the profound .
Influence of vitamin d status and vitamin d3 supplementation on genome wide expression of white blood cells. No studies have reported on how vitamin D status and vitamin D3 supplementation affects broad gene expression in humans. A randomized, double-blind, single center pilot trial was conducted for comparing vitamin D supplementation with either 400 IUs (n = 3) or 2000 IUs (n = 5) vitamin D3 daily for 2 months on broad gene expression in the white blood cells collected from 8 healthy adults. in the winter. CONCLUSION SIGNIFICANCE: Our data suggest that any improvement in vitamin D status will significantly affect expression of genes that have a wide variety of biologic functions of more than 160 pathways linked to cancer, autoimmune disorders and cardiovascular disease with have been associated with vitamin D deficiency. This study reveals for the first time molecular finger prints that help explain the nonskeletal health benefits of vitamin D
Tehran University http://www.ncbi.nlm.nih.gov/pubmed/23517460 showed clearly that Vitamin D Supplementation Improve the Severity of Congestive Heart Failure. In 100 heart failure patients with (NYHA) class I , Only 6% of the participants had a sufficient serum concentration of 25(OH) D >30 nmol/L. Patients with insufficient or deficient serum levels of 25(OH) D (<30 ng/mL and <20 ng/mL, respectively) received oral vitamin D3 for 4 months. Vitamin D supplement increased mean serum 25(OH) D from 12.6 nmol/L to 54 nmol/L (P<.001). After vitamin D supplement, the serum level of pro-brain natriuretic peptide markedly decreased (P<.001). Cholecalciferol significantly decreased high-sensitivity C-reactive protein level (P<.001). Restoration of serum 25(OH) D level was also associated with substantial improvement in hear tfailure (P<.001) and 6-minute walk distance (P<.001).
and Robert Heaney’s group at Creighton University http://www.ncbi.nlm.nih.gov/pubmed/23514768 that . All-Source Basal Vitamin D Inputs Are Greater Than Previously Thought and Cutaneous Inputs Are Smaller.
The magnitude of vitamin D inputs in individuals not taking supplements is unknown.. they reanalyzed 3000 subjects’ individual 25(OH)D concentration data from 8 studies involving vitD3 supplement. The total basal input (food plus solar) was calculated to range from a low of 778 iu/d in patients with end-stage renal disease to a high of 2667 iu/d in healthy Caucasian adults. Consistent with expectations, obese individuals had lower baseline, unsupplemented 25(OH)D concentrations and a smaller response to supplements. Similarly, African Americans had both lower baseline concentrations and lower calculated basal, all-source inputs. Seasonal oscillation in 4 studies ranged from 5.20 to 11.4 nmol/L, reflecting a mean cutaneous synthesis of cholecalciferol ranging from 209 to 651 iu/d at the summer peak. We conclude that: 1) all-source, basal vitamin D inputs are approximately an order of magnitude higher than can be explained by traditional food sources; 2) cutaneous, solar input in these cohorts accounts for only 10-25% of unsupplemented input at the summer peak; and 3) the remainder must come from undocumented food sources, possibly in part as preformed 25(OH).
Update March 2010
August 2009 SUMMARY: Evidence is overwhelming that the prime sun-induced steroid hormone Vitamin D3 cholecalciferol – soltriol- is invaluable in 20fold higher dose ie perhaps 5000 to 10 000iu/day rather than has been preached to date (200- 400iu/d), as part of lifelong hormone replacement HRT to prevent all major chronic degenerative diseases in all humans living and working indoors. Effective dose of vitamin D3 supplement can reduce deathrate and disease by an astonishing 20%- that is indeed a panacea almost as good as other natural micronutrient supplements eg fish oil, metformin, and appropriate sex hormone replacement SHRT. It is becoming clear that with rare exceptions everyone- especially those with serious disease eg cancer, heart, lung, brain, nerve/muscle/bone/joint or inflammatory bowel diseases or chronic infections like TB HIV influenza or human papilloma virus – should take a daily supplement of about 10 000iu (1/4 mg) vitamin D for as little as ~ R10 US$1 a month ; ideally under supervision of some health professional. All that is required is occasional check of blood chemistry, and good diet and fluid intake.
And obviously because of vitamin D3’s benefits in lowering all diseases, when using vigorous dose vitamin D, one must expect to need to lower prescription drug treatments for diabetes, hypertension, depression, heart disease, lung disease, arthritis, infections etc as these ailments improve from the vitamin D replacement over months.
INTRODUCTION: Battling to help some desperate patients this week – mostly women- with cancer, vascular, rheumatoid, lupus, diabetic, depressive, osteoporotic and infective disease- especially now the quadruple perils of infections – influenza; human papilloma virus; AIDS and tuberculosis – let alone nuisances like shingles candida or herpes – prompts a thorough review of the polyfunctional vitamin of this decade- vitamin D3, cholecalciferol, soltriol (Stumpf WE).
This review is especially appropriate on our Womens’ Day 9 August 2009 for a natural product so important for the health of women , that commemorates the year 1956 when 20 000 women marched in defiance of male despots’ fascist apartheid pass laws. The ages-old discrimination against women is epitomized by the pragmatic liberal economist Professor Ken Galbraith’s lecture to the Royal Society of Medicine in 1973 on the problem of unequal development and centralization of power in male technostructure – profit maximization.
No-where in business is this better shown than in Big Business creating demand by saturation marketing, including the medicalization of health. This involves disease-mongering through creating unnecessary concerns so as to expand markets among the well for patents eg blanket cholesterol or mammography or colonoscopy screening, or remedies for eg female arousal disorder, anxiety, reactive depression, mild-to-moderate hypercholesterolemia – when very few have been proven to need or benefit from such labels, procedures and drugs.
VITAMIN D3 SOLTRIOL : INFORMATION EXPLOSION:
The first of 46200 entries on Medline on vitamin D is from Oxford by Heaton 1922 . There are 272 500 entries on vitamins since 1918, the first specific one by Jack Drummond in 192o, but of course vitamin D was first identified by Mellanby 1919, preceded by vits A, B1 and C between 1909 and 1912. From a recent historical review (table 1) of hormones, vitamin D3 was perhaps the 7th hormone recognized after testosterone and estrogen (China 2600 years ago) , thyroid (1891) epinephrine secretin parathyroid and antidiuretic hormone.
Soltriol is an exquisite description for a sun-activated steroid, the cardinal prohormone vitamin D3 made from cholesterol via sunlight exposure. Soltriol is not in a 1964 Oxford Dictionary, nor is it’s etymology detectable on Google search; it was indeed invented by the pioneer polymath neurologist Dr Walter Stumpf . On Medline search for soltriol, the first result is Corradino 1973…
It is intriguing to read that Dr Stumpf graduated in medicine in 1952- and 50 years later in 2005 he wrote on his website: “From the microautoradiographic target recognition and related actions it follows that vitamin D has healing potential for prevention and treatment of various deficiencies and ailments, including old age: a PANACEA? If there is any compound that deserves being designated a panacea, the multifunctional heliogenic vitamin D appears a suitable candidate. Philosophical consideration: “Vitamin D”, the term does not reflect its significance. I have used instead SOLTRIOL in several publications as a more appropriate designation. – Is there not a link to Heraclitus emanation of “ ever-living fire ”? The cosmic solar fire (Soltriol) as the sustaining life force, providing wave length energies for Temperature, Visible Light , and Ultraviolet B “. ” The Main Biological Role of Vitamin D is Seasonal Adjustment of Vital Functions: These include regulation of growth, reproduction, survival stress response; endocrine and exocrine secretion, cell proliferation, cognition and mood; neuro-motor, neuro-endocrine, and neuro-sensory functions, immune response, cardio-vascular and gastro-intestinal functions, regulation of calcium and other mineral levels, cell proliferation and protein synthesis-differentiation.
Considering the decades of vitamin D use for its other benefits, it is ironic that a 1999 University California website on The History of Vitamin D has never been updated to cover more than the anti-rickets protection from vitamin D. But as Prof Stumpf writes to me today, ultimately it is the sun that is the panacea, transmitting it’s healing powers via the skin-activated messenger hormone vitamin D.
It is now almost a year since this column last reviewed vitamin D3’s benefits against all major diseases (see table) – during which year scores of new randomized controlled trials RCTs of vitamin D have appeared- there are now some 1680 RCTs on it since 1965. Carpenter 1999 reviews Forgotten Mysteries in the History of Vitamin D.
Women have a raw deal: due to their prime role and innate sense for survival of the species, for nuturing and caring, they live about 10% longer than their mates, but as a result endure far more illness, as well as assault, disability and murder (mostly inflicted by the careless male).
PROTEAN STEROIDS, PROTEAN FUNCTIONS: Calcitriol is one of many human steroids that include the sex hormones, aldosterne and digoxin; as well as nonhuman steroids which also have important medicinal use- like phytosteroids, equine steroids like the equilins eg premarin, and the important ecdysteroids in insects and some plants. Stumpf has again stressed the wide distribution in humans of vitamin D receptors VDRs, indicating their importance in protean human functions far beyond calcium regulation.
VITAMIN D AND ALL-CAUSE MORTALITY: it is just a year since Melamed ea from USA showed that having low vitamin D (as opposed to high level) increases all-cause mortality by 26%- thus taking submaximum safe dose of vitamin D can improve chance of survival by about 20%. This for as little as R10/month – $1- in South Africa.
In 2000, the Seven Country Study Group showed that ” saturated fat,vitamin C and smoking are the major determinants of all-causemortality at the population level” ie the higher the fat and smoking intake and the lower the vitamin C, the higher the deathrate. We now know better- serious vitamin D deficiency joins the list, which of course includes alcoholism. .
VITAMIN D AND CARDIOVASCULAR DISEASE CVD
Pizzorno 2009 reviews the strong evidence of the importance of balanced vitamins A D and K supplements in reversing the epidemics of both CVD and osteoporosis.
VITAMIN D AND DEPRESSIVE/NEURODEGENERATIVE DISEASE
over 20 articles already this year attest to the importance of vigorous vitamin D levels in reducing these diseases.
VITAMIN D AND AUTOIMMUNE / INFLAMMATORY BOWEL DISEASE AND MUSKULOSKELETAL DISEASE:
The much higher incidence of autoimmune diseases in women – especially SLE systemic lupus erythematosis and RA rheumatoid arthritis- let alone far higher younger female risk for fractures- must have been obvious for millennia. So obviously genetic female factors play a major role in these diseases – now surely attributable largely to the reproductively necessary absence of the Y chromosome, and thus the 100fold lower testosterone: estradiol T:E2 ratio in women (perhaps 2:1) than in men (in youth, >200:1).. It is common cause that estrogen is immunostimulant whereas testosterone and progesterone (like vitamin D) are immunomodulating. Hence testosterone and progesterone levels soar during pregnancy to prevent the mother rejecting her foetus. This partly also explains why vigorous vitamin D supplement also greatly improves fertility and pregnancy outcome.
VITAMIN D AND RHEUMATOID ARTHRITIS: many studies show the benefits of the prime anabolic steroids- vitamin D and androgen (Devis 1950) supplements- in treatment of all inflammatory disease, especially when inflammation itself weakens bone and all other tissues. The latest – last month (Chabchoub 2009)- shows “a possible role for XCI mosaicism in the pathogenesis of RA and thyroid disease and may in part explain the female preponderance of these diseases”. But the first and only randomized controlled trial of the effect of vitamin D on modifying RA appears in 1973 (Brohult) and the only open trial (Andjelkovic 1999) in RA showed that “alphacalcidiol is a powerful immunomodulatory agent with fairly low hypercalcemic activity”.
VITAMIN D INTOXICATION: The low toxicity of vitamin D3 is fortunate because while it is ideal to monitor vitamin D levels on effective replacement, the blood test costs about R660- $80- locally; hence all one needs to do is exclude kidney problems (which may need even higher dose of vitamin D3), and risk of kidney stones- but perhaps checking blood calcium and creatinine at baseline and occasionally, and ensuring balanced supplement of calcium-magnesium – boron-zinc-manganese-(iron if deficient) and vitamins B, C, D and K. Since vitamin D intoxication (toxic rise in blood calcium- hypercalcemia) in some opinions requires ~>600 000iu/day for months, ths is inconceivable unless one were to swallow say twelve 50 000iu vitamin D every day for months. So the only recognized form of vitamin D intoxication could be an industrial accident involving mistaken use of vitamin D concentrate in medicine.
HYPERCALCEMIA HIGH BLOOD CALCIUM: medical causes are rare without gross calcium overdose (milk alkali syndrome) or other specific symptomatic diseases – eg primary hyperparathyroidism, sarcoidosis, tuberculosis, and lymphoma.And fortunately most patients with these diseases and hypercalcemia are far more likely to benefit from therapeutic treatment with vitamin D than worsen on it.
OVERDOSE: HYPERVITAMINOSIS D: WIKI says “Vitamin D stored in the human body as calcidiol (25-hydroxy-vitamin D) has a half-life of about 20 to 29 days.[17] Ordinarily, the synthesis of bioactive vitamin D hormone is tightly regulated, and prevalent thinking is that vitamin D toxicity usually occurs only if excessive doses (prescription forms or rodenticide[38] . Serum levels of calcidiol (25-hydroxy-vitamin D) are typically used to diagnose vitamin D overdose. In healthy individuals, calcidiol levels are normally between 32 to 70 ng/mL (80 to 175 nmol/L), but these levels may be as much as 15-fold greater in cases of vitamin D toxicity. Serum levels of bioactive vitamin D hormone (1,25(OH2)D) are usually normal in cases of vitamin D overdose. Symptoms include Dehydration Vomiting Decreased appetite (anorexia) Irritability Constipation Fatigue.
Overdose of vit D3 has been observed at 1925 µg/d (77,000 IU per day). Acute overdose requires between 600,000 and 1,680,000 IU per day over a period of several days to months, with a safe intake level being 10,000 IU per day.
A 2007 risk assessment suggested that 250 micrograms/day (10,000 IU) in healthy adults should be adopted as the tolerable upper limit.[39] In adults, sustained intake of 100,000 IU can produce toxicity within a few months.[2] For infants (birth to 12 months) the tolerable UL is set at 1000 IU, and 40,000 IU has been shown to produce toxicity within 1 to 4 months. All known cases of vitamin D toxicity with hypercalcemia have involved intake of or over 40,000 IU)[42].
Although normal food and pill vitamin D concentration levels are far too low to be toxic in adults, people taking multiples of the normal dose of codliver oil may reach toxic levels of vitamin A, not vitamin D, [43] if taken in an attempt to increase the levels of vitamin D. Most officially-recorded historical cases of vitamin D overdose have occurred due to manufacturing and industrial accidents.[42]
Some symptoms of vitamin D toxicity are a result of hypercalcemia caused by increased intestinal calcium absorption. Vitamin D toxicity is known to be a cause of high blood pressure.[45] Gastrointestinal symptoms of vitamin D toxicity can include anorexia, nausea, and vomiting. These symptoms are often followed by polyuria (excessive production of urine), polydipsia (increased thirst), weakness, nervousness, pruritus (itch), and eventually renal failure. Other signals of kidney disease including elevated protein levels in the urine, urinary casts, and a build up of wastes in the blood stream can also develop.[2] In one study, hypercalciuria and bone loss occurred in four patients with documented vitamin D toxicity.[46] Another study showed elevated risk of ischaemic heart disease when 25D was above 89 ng/mL.[47] Vitamin D toxicity is treated by discontinuing vitamin D supplementation, and restricting calcium intake. If the toxicity is severe blood calcium levels can be further reduced with corticosteroids or bisphosphonates. In some cases kidney damage may be irreversible.[2]
Exposure to sunlight for extended periods of time does not normally cause vitamin D toxicity.[42] This is because within about 20 minutes of ultraviolet exposure in light skinned individuals (3–6 times longer for pigmented skin) the concentration of vitamin D precursors produced in the skin reach an equilibrium, and any further vitamin D that is produced is degraded.[48] Maximum endogenous production with full body exposure to sunlight is 250 µg (10,000 IU) per day.[42]”
VITAMIN D AND SEX:
Biologically, the most imperative function for species survival is sex- reproduction. Vitamin D is clearly a potent anabolic reproductive steroid like testosterone: The first paper on this association on Pubmed appears in 1963 from Russia (Gokinaeva).
Stumpf 1989 at Univ N Carolina reported that “vitamin D (soltriol) regulates and modulates reproductive processes in the female and male, controlling reproductive processes from onset of puberty to fertility, pregnancy, lactation, and probably sexual behavior.”
Mirzahossein in 1996 showed that,” given in the critical period of foetal imprinting, vitamin D may influence steroid hormone-receptor commanded events for life in a way similar to synthetic steroid hormone analogues”. So as with marine omega3., it is crucial that future parents take enough vitamin D.
Friedrich 2002 showed that even prostate, colon and normal cervical tissue and cervical cancer cells have VDRs – vit D receptors- and may be new targets for cancer prevention or cancer treatment.
Kalueff 2005 showed that it influences even neurological receptors eg grooming behaviour in mammals.
And now Blauer 2009 shows that it reduces growth by up to 60% in human uterus muscle and fibroids- leiomyomas.
VITAMIN D AND PAIN: this week Khan ea from Kansas University describe Effect of vitamin D supplement on joint pain and fatigue in women starting adjuvant letrozole treatment for breast cancer. But the first Pubmed reference on vitamin D and pain is from von Wendt 1951. Gerwin 2005 recognized vitamin D deficiency as a cause of fibromyalgia- chronic fatigue syndrome.
and Glueck ea from Cincinnati show that vitamin D supplement for low vitamin D abolishes statin – induced myalgia.
VITAMIN D AND SLE- SYSTEMIC LUPUS ERYTHEMATOSIS: on medline the first reference to immunosuppression with vitamin D was by Bourdial 1963 on nasal allergy, and the first for vitamin D and immunomodulation is by Nagler & Pollack 1986.:
However, the first paper on the importance of Vitamin D3 deficiency in SLE appeared in Germany 1963, but the first paper in English and from an English country only in 1979 (O’Regan).
The focus throughout has been on the benefit of vitamin D in reversing the hyperimmunity of SLE, but of course vitamin D is equally important in preventing both the osteoporosis of inflammation, the fracture and wasting risks of cortisone treatment, and the vascular disease associated with SLE. In the last year alone there have been 10 such SLE – vitamin D major studies – 7 from the Americas and 3 from Europe.
SLE as well as plain lupus of the skin are generally regarded as disease that requires protection from the sun.
Now this week Wright 2009 shows that in children, SLE is associated with vitamin D deficiency, particularly among those subjects with SLE who are overweight.
VITAMIN D, SUNLIGHT, SLE AND CANCER:
The first case of SLE associated with cancer ( meningioma and cervix)- is reported by Williams 1956. The latest – last month- highlights increased risk of lymphoma, cervix and bronchus cancers.
Search for malignant melanoma MM and SLE finds the first reference in 1963. yet most of the papers are about reactions to interferon therapy, or immune markers- there is one solitary case report (1991 Sulkes, Israel) of a patient with indolent SLE who after 15 years developed and died of rapidly spread of MM. These authors comment on the infrequent association of SLE & solid cancers, the commonest being uterus and bladder.
So it is exciting that while more sun exposure causes skin cancer and especially cutaneous melanoma CMM, (Tuohimaa 2007), sun exposure also improves survival from CMM- and from a wide range of internal cancers – (especially stomach, colorectal, liver and gallbladder, pancreas, lung, female breast, prostate, bladder and kidney cancers). This favourable effect of more sunshine is obvious when comparing the lower cancer and heart disease deathrates in sunnier southern versus the darker northern countries. Only rare skin diseases eg porphyria cutanea tarda are contraindications to sun exposure of the skin. But at least one study Holme 2008 shows vitamin D deficiency in erythropoetic porphyria.
Professor Halstead 2008 (and many others) conclude that the high fructose corn syrup routinely used in fast foods and cooldrinks in first-world manufacturing is rapidly increasing obesity, lipidemia (and metabolic syndrome and cancer); while folic acid food fortification is causing low B12 levels and thus possibly increasing dementia, vascular disease and advanced precancerous colorectal adenomas and breast cancer. This trend is aggravated by at least three scientifically unvalidated obsessions of Regulators and the Medical hierarchy:
1. low diet cholesterol in those with mild to moderate cholesterolemia;
ii. low vitamin D – low intake dairy products and less sunlight exposure for fear of skin cancer; and
iii. warfarin (which blocks essential vitamin K) to reduce thromboses- whereas it worsens both fracture risk and vitamin D and K deficiency, and thus arterial calcification, cancer and fractures; all of which are reversed by vigorous vitamin B3-6-9-12 , C, D & K supplementation.
Protection from both cancers and SLE is probably associated with higher vitamin D level above ~100nmol/L. Both lupus and cancers are due to altered immunity. But SLE is due to increased autoimmunity- hence cancers are infrequent during active SLE; whereas cancers are due to reduced immunity – hence are associated with immune suppression, whether by cortisone (including stress) / chemotherapy, or deficiency of vitamin D – dietary and lack of sunshine..
It is now common cause that more cancers occur with suppressed blood cholesterol – whether the low cholesterol is cause d by or due to the cancer remains to be clarified; and at least one of the major statin cholesterol-lowering trials showed increase in breast cancer cases.
While there is no clear overall relationship of statins to osteoporosis or cancer, Kunitomo 1989showed that cholesterol reduces and corticosteroids enhance the toxicity of vitamin D in rats. Montagnani 1994 showed that pravastain does not interfere with the circulating levels of the main vitamin D metabolites.
VITAMIN D AND INFECTION:
For an acute infection, Cannell and Hollis 2008 suggest vitamin D in an antimicrobial dose of 2000iu/kg eg 120 000 iu a day for 3 days- to produce enough of the naturally occuring antibiotic cathilicidin. Ginde 2009 show that those with high vitamin D levels have less respiratory infections. This column has previously reviewed the dramatic benefits of vitamin D on infection mortality in AIDs- TB patients. Obviously one is going to be cautious pushing vitamin D in a patient with known kidney stones, or hypercalcemia.
VITAMIN D : WHY THE INCREASING DEFICIENCY, NEED FOR SUPPLEMENT ?
Never mind the poor and chronically ill, the aging especially need much more vitamin D, and benefit the most. Even in a sunny fishing nation like Spain, elderly women do not get enough vitamin D from fish or other foods, and most have suboptimal blood levels of it.
Apart from dietary intolerance and obsession reducing intake of cholesterol and dairy products, the vitamins and minerals in particular have been greatly depleted and imbalanced in commercially produced- and especially genetically-modified food. And while increasing longevity, food scarcity -poverty and mushrooming prices (cartel pricefixing that is ignored by well-paid politicians and regulators) – are prime causes, Politicians and Regulators have worsened this by falling decades behind in ignoring the leading 20th pioneer nutritionist/ economists like the USA’s Professors Linus Pauling the unique double Nobel prizewinner prophet of vitamin C and peace; Ken Galbraith; and the UK’s Sir Jack Drummond. The latter two respectively brought the Allies (under FD Rooseveld and WS Churchill) through WW2 by putting farming- healthy food production and pricing- as the painfully obvious priority- which selfserving gluttonous politicians like Nixon, Bush, Kissinger, Mugabe and Mbeki, and most others leaders (who support, not just tolerate such despots) simply ignore since they detest “surplus people”- the honest poor; if not also hardworking farmers.
It is no coincidence that Pauling and Galbraith both graduated from agricultural colleges. And no coincidence that all three nutritionists were the targets of politician-business moguls because of the obstacles they posed to the profiteering national economic sabotage that is the lifeblood of ruthless businessmen-capitalists from before Nixon- Connolly- Reagan- Kissinger and Thatcher, through to the Bushes and Blair and Montsano-GD Searle, Mbeki and Zuma, and the arms, oil, banking, mining, media, food, sex, tobacco-alcohol and medical-big pharma industry mafiosi cartel who make or break presidents and governments.
James Ferguson makes a strong case for The Vitamin Murders, that Drummond (and his family) were butchered in a Vitamin Industry contract in France as a lesson to do-gooders because his advocacy of the primary role of good natural nutrition and vitamins was such an obstacle to the fast food and synthetic drug industry. Conspiracy theorists could argue that, like Pauling’s vitamin C, the Drug Industry have through the FDA managed to ensure that only this year is the FDA grudgingly moving to raise the Recommended daily Allowances of vitamin D (and C) even fractionally above the present rickets- (and scurvy) preventing doses, as opposed to their modest 25 to 50fold fold higher intakes that have been known already for decades to be both safe and major benefit against all diseases.
John Le Carre’s The Constant Gardner echoes that ongoing conspiracy scenario, the battle between Big Pharma with it’s drug lobbyists (including the USA FDA and the European Union’s European Medicine’s Authority, and leading politicians) to promote their lucrative modern synthetic chronic drugs (none of which have been shown to reduce all-cause disease and mortality as do natural supplements), versus nutritionists and informed consumers who know that broad natural supplements (vigorous vitamins, minerals and biologicals) to bolster the failing adulterated food chain are more important and effective than any patented designer drugs in combating all disease. Unfortunately the necessary advocacy for natural supplements has been muddied by fraudsters like the Big Pharma- FDA- academia cartel (who swamp the medical literature with trial and review papers favouring their snake oils), the Rath Foundation, and our local dissidents against reason like Mbeki, and Drs Manto Tshabalala-Msimang, Nkosasama Zuma and Olive Shishana.
CONCLUSION: In 2006 Dr Walter Stumpf in THE DOSE MAKES THE MEDICINE wrote: “in recent years, discussion raged about the negative effects of estrogen-replacement therapy and its relationship to cancer. In numerous articles, the side-effects of estrogen treatment were highlighted in a generalized fashion and, although consideration was given to the duration of treatment, the relationships to dose (let alone type and route of estrogen) were frequently left out. And yet, considerations of dose and time in pharmacology and toxicology are paramount.
Similarly, awareness of proper dosage is crucial to the development of future vitamin D therapies. Physiologic dosing of vitamin D does not cause hypercalcemia – hypercalcemia is related to overdosing ie closer to 100 000iu/day. Considering the many target tissues that are unrelated to systemic calcium regulation, most therapeutic effects of vitamin D occur independently of the high-dose systemic calcium effects. Because of the biased focus on calcium, the many other effects tend to remain unnoticed and hidden. Future research needs to give more consideration to dose-effect relationships by monitoring target functions independently of systemic calcium regulation.
New therapeutic applications of vitamin D can be established for cardiovascular, neurological, endocrine, immune, gastrointestinal, reproductive and other diseases, including posttraumatic and gerontological deficiencies, in which the polyfunctional effects of the hormone not only come to bear, but can also be controlled and maximized for optimal health.”
Since the global population shift from rural to city life and work the past century ie in our lifetispan, humans have largely gone from being healthy longlived outdoor food-producing workers living on their own fresh produce including organically grown unadulterated fresh food and dairy products – or fish- (rich in micronutrients), to working mostly indoors and consuming largely micronutrient-depleted food as well as multiple noxious deliberate industrial pollutants- from sugar and alcohol to estrogenics, pesticides, heavy metals, cornsyrup and aspartamate.
Like fish oil is the most important food extract we have (and businessmen are ruthlessly harvesting to extinction), vitamin D3 has become the anti-disease vitamin of the past decade, joining vitamins C & B as the panacea vitamins that can and should be supplemented in far higher dose than anti-vitamin “Regulators” and professional researchers and associations (with vested interests in protecting their funder- Big Pharma) approve.
But as the more affluent age and increase in numbers, the micronutrients that deplete (with longevity, the deteriorating food chain, and unnecessary drugs),- especially vitamins K, chondroglucosamine, N-acetyl cysteine, alphalipoic acid, Co-Q10, arginine, carnitine, carnosine, riboseand the marine EPA and DHA- are fast becoming the “vitamins” of the next decade.
Tragically, edible marine products especially marine omega3 EPA+DHA are rapidly becoming so scarce that the vast majority of people can neither source nor afford the minimum optimal gram a day, until science breaks through to synthesize these uniquely beneficial free fatty acids. But at least the supply of minerals, and vitamins including D3, is inexhaustible and therefore freely available at reasonable cost.
ndb
dedicated to Dr Walter Stumpf, whose >300 papers (~24% on vitamin D) on Medline apparently span 1963 to 2008- on vitamin D the first in 1979, the last 30years later appropriately on Vitamin D and the digestive system. By comparison, Pubmed lists only 3 papers by Albright, in 1938-9.
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