Randomized comparison of the effects of the vitamin D3 adequate intake versus 100 mcg (4000 IU) per day on biochemical responses and the wellbeing of patients.
Vieth R, Kimball S, Hu A, Walfish PG.
Nutr J. 2004 Jul 19;3:8.
PMID: 15260882
doi:10.1186/1475-2891-3-8
CONCLUSION: The highest AI for vitamin D brought summertime 25(OH)D to >40 nmol/L, lowered PTH, and its use was associated with improved wellbeing. The 100 mcg/day dose produced greater responses. Since it was ethically necessary to provide a meaningful dose of vitamin D to these insufficient patients, we cannot rule out a placebo wellbeing response, particularly for those on the lower dose. This work confirms the safety and efficacy of both 15 and 100 mcg/day vitamin D3 in patients who needed additional vitamin D.
P.T. Liu, S. Stenger, H. Li, L. Wenzel, B.H. Tan, S.R. Krutzik, M.T. Ochoa, J. Schauber, K. Wu, C. Meinken, et al.\nVitamin D3-Triggered Antimicrobial Response--Another Pleiotropic Effect beyond Mineral and Bone Metabolism: Toll-Like Receptor Triggering of a Vitamin D-Mediated Human Antimicrobial Response. Science 311: 1770-1773, 2006\nJ. Am. Soc. Nephrol., November 1, 2006; 17(11): 2949 - 2953.
Conclusion
The data point to a critical role for the VDR and 1,25(OH)2D3 in control of innate immunity and the response of the colon to chemical injury.
Vitamin D and the vitamin D receptor are critical for control of the innate immune response to colonic injury.
Froicu M, Cantorna MT.
BMC Immunol. 2007 Mar 30;8:5.
PMID: 17397543
doi:10.1186/1471-2172-8-5
Conclusion
We demonstrated that the VDRE in the CAMP gene originated from the exaptation of an AluSx SINE in the lineage leading to humans, apes, OWMs and NWMs and remained under purifying selection for the last 55-60 million years. We present convincing evidence of an evolutionarily fixed, Alu-mediated divergence in steroid hormone nuclear receptor gene regulation between humans/primates and other mammals. Evolutionary selection to place the primate CAMP gene under regulation of the vitamin D pathway potentiates the innate immune response and may counter the anti-inflammatory properties of vitamin D.
Exaptation of an ancient Alu short interspersed element provides a highly conserved vitamin D-mediated innate immune response in humans and primates.
Gombart AF, Saito T, Koeffler HP.
BMC Genomics. 2009 Jul 16;10:321.
PMID: 19607716
doi:10.1186/1471-2164-10-321
True to form, Dr. John Cannell has published yet another wonderfully insightful Vitamin D Newsletter.
One item caught my eye, a response to a question about the Marshall Protocol. I, like Dr. Cannell, was inundated with questions about this so-called protocol, which amounts to little more than the unfounded speculations of a non-physician, actually someone not even involved in health care.
In all honesty, I blew the whole issue off after I read Dr. Marshall's rants. They smack of pure quackery, though from somebody who clearly has a command of scientific lingo. To Dr. Cannell's credit, he took the time and effort to construct a rational response in the latest issue of the newsletter. I reproduce his response here:
Vitamin D deficiency is the cause of common obesity.
Foss YJ.
Med Hypotheses. 2009 Mar;72(3):314-21. Epub 2008 Dec 2.
PMID: 19054627
doi:10.1016/j.mehy.2008.10.005
Common obesity and the metabolic syndrome may therefore result from an anomalous adaptive winter response. The stimulus for the winter response is proposed to be a fall in vitamin D. The synthesis of vitamin D is dependent upon the absorption of radiation in the ultraviolet-B range of sunlight. At ground level at mid-latitudes, UV-B radiation falls in the autumn and becomes negligible in winter. It has previously been proposed that vitamin D evolved in primitive organisms as a UV-B sensitive photoreceptor with the function of signaling changes in sunlight intensity. It is here proposed that a fall in vitamin D in the form of circulating calcidiol is the stimulus for the winter response, which consists of an accumulation of fat mass (obesity) and the induction of a winter metabolism (the metabolic syndrome). Vitamin D deficiency can account for the secular trends in the prevalence of obesity and for individual differences in its onset and severity. It may be possible to reverse the increasing prevalence of obesity by improving vitamin D status.
The vitamin D-antimicrobial peptide pathway and its role in protection against infection.
Gombart AF.
Future Microbiol. 2009 Nov;4:1151-65.
PMID: 19895218
Vitamin D deficiency has been correlated with increased rates of infection. Since the early 19th century, both environmental (i.e., sunlight) and dietary sources (cod liver) of vitamin D have been identified as treatments for TB. The recent discovery that vitamin D induces antimicrobial peptide gene expression explains, in part, the 'antibiotic' effect of vitamin D and has greatly renewed interest in the ability of vitamin D to improve immune function. Subsequent work indicates that this regulation is biologically important for the response of the innate immune system to wounds and infection and that deficiency may lead to suboptimal responses toward bacterial and viral infections. The regulation of the cathelicidin antimicrobial peptide gene is a human/primate-specific adaptation and is not conserved in other mammals. The capacity of the vitamin D receptor to act as a high-affinity receptor for vitamin D and a low-affinity receptor for secondary bile acids and potentially other novel nutritional compounds suggests that the evolutionary selection to place the cathelicidin gene under control of the vitamin D receptor allows for its regulation under both endocrine and xenobiotic response systems. Future studies in both humans and humanized mouse models will elucidate the importance of this regulation and lead to the development of potential therapeutic applications
Vitamin D intake to attain a desired serum 25-hydroxyvitamin D concentration.
Aloia JF, Patel M, Dimaano R, Li-Ng M, Talwar SA, Mikhail M, Pollack S, Yeh JK.
Am J Clin Nutr. 2008 Jun;87(6):1952-8.
PMID: 18541590
The mean daily dose was 86 microg (3440 IU). The use of computer simulations to obtain the most participants within the range of 75-220 nmol/L predicted an optimal daily dose of 115 microg/d (4600 IU). No hypercalcemia or hypercalciuria was observed. CONCLUSIONS: Determination of the intake required to attain serum 25(OH)D concentrations >75 nmol/L must consider the wide variability in the dose-response curve and basal 25(OH)D concentrations. Projection of the dose-response curves observed in this convenience sample onto the population of the third National Health and Nutrition Examination Survey suggests a dose of 95 microg/d (3800 IU) for those above a 25(OH)D threshold of 55 nmol/L and a dose of 125 microg/d (5000 IU) for those below that threshold.
Plasma vitamin D and 25OHD responses of young and old men to supplementation with vitamin D3.
Harris SS, Dawson-Hughes B.
J Am Coll Nutr. 2002 Aug;21(4):357-62.
PMID: 12166534
Conclusions: There appears to be no age-related impairment among men in the absorption or metabolism of 20 µg/day of vitamin D3 taken orally for at least eight weeks.
"(NaturalNews) People still don't get it: Vitamin D is the "miracle nutrient" that activates your immune system to defend you against invading microorganisms -- including seasonal flu and swine flu. Two months ago, an important study was published by researchers at Oregon State University. This study reveals something startling: Vitamin D is so crucial to the functioning of your immune system that the ability of vitamin D to boost immune function and destroy invading microorganisms has been conserved in the genome for over 60 million years of evolution.
As this press release from Oregon State University (http://www.eurekalert.org/pub_relea...) explains:
The fact that this vitamin-D mediated immune response has been retained through millions of years of evolutionary selection, and is still found in species ranging from squirrel monkeys to baboons and humans, suggests that it must be critical to their survival, researchers say.
"The existence and importance of this part of our immune response makes it clear that humans and other primates need to maintain sufficient levels of vitamin D," said Adrian Gombart, an associate professor of biochemistry and a principal investigator with the Linus Pauling Institute at Oregon State University."
A positive dose-response effect of vitamin D supplementation on site-specific bone mineral augmentation in adolescent girls: a double-blinded randomized placebo-controlled 1-year intervention.
Viljakainen HT, Natri AM, Kärkkäinen M, Huttunen MM, Palssa A, Jakobsen J, Cashman KD, Mølgaard C, Lamberg-Allardt C.
J Bone Miner Res. 2006 Jun;21(6):836-44.
PMID: 16753014
doi: 10.1359/jbmr.060302
We conclude that the current vitamin D recommendation for adolescent girls, at least in the northern latitudes, is too low to ensure sufficient vitamin D status during winter. Intake of vitamin D at rates of 10-15 μg/day aids to maintain stable S-25(OH)D concentrations during winter. Vitamin D induced BMC augmentation by decreasing bone resorption, but not affecting bone formation, which was reflected by the biochemical markers of bone turnover. Optimizing bone mineral gain in adolescence is crucial to the prevention of osteoporosis later in life. Increasing vitamin D intake to 10-15 μg/day aids in attaining this goal.
Vitamin D plays a critical role in the human body's response to tuberculosis, according to new research that explains why people of African descent are more susceptible to TB.
The research also suggests a new way to fight one of the world's deadliest diseases: with a simple dietary supplement. Tuberculosis, usually caused when a person inhales tuberculosis bacteria, killed an estimated 1.7 million people in 2003 and is the leading cause of death for people afflicted with AIDS, according to the World Health Organization (WHO).
BACKGROUND: To determine the effect of vitamin D binding protein (DBP) genotypes on 25-hydroxyvitamin D [25(OH)D] changes with vitamin D supplements, we studied 98 adults receiving 600 or 4000 IU/d vitamin D(3) for one year. METHODS: The DBP functional variant, T436K, was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: Mean 25(OH)D increases were 97% for TT (n=48), 151% for TK (n=31) and 307% (n=6) for KK genotypes (p=.004). CONCLUSIONS: As with baseline 25(OH)D, T436K genotype predicts 25(OH)D changes after long-term vitamin D supplementation.
Common genetic variants of the vitamin D binding protein (DBP) predict differences in response of serum 25-hydroxyvitamin D [25(OH)D] to vitamin D supplementation.
Fu L, Yun F, Oczak M, Wong BY, Vieth R, Cole DE.
Clin Biochem. 2009 Jul;42(10-11):1174-7. Epub 2009 Mar 18.
PMID: 19302999
Together, the earlier data and the data of Heaney et al indicate that an oral dose of vitamin D2 or vitamin D3 would lead to a comparable increase in circulating 25(OH)D concentrations in children and adults when the initial 25(OH)D3 concentrations in the groups are similar and when equivalent oral vitamin D doses expressed per kilogram body weight/d are given.
Serum 25-hydroxyvitamin D response to oral vitamin D intake in children.
Zittermann A.
Am J Clin Nutr. 2003 Sep;78(3):496-7.
PMID: 12936937
Improved cholecalciferol nutrition in rats is noncalcemic, suppresses parathyroid hormone and increases responsiveness to 1, 25-dihydroxycholecalciferol.
Vieth R, Milojevic S, Peltekova V.
J Nutr. 2000 Mar;130(3):578-84.
PMID: 10702588
We conclude suppression of 1,25(OH)(2)D and PTH, and higher renal VDR mRNA and 24-hydroxylase did not involve higher free 1,25(OH)(2)D concentration or a first pass effect at the gut. Thus, 25(OH)D or a metabolite other than 1,25(OH)(2)D is a physiological, transcriptionally and biochemically active, noncalcemic vitamin D metabolite.
When viewed from a perspective that starts with higher vitamin D nutrition, the results indicate that low vitamin D nutrition may bring about a form of resistance to 1,25(OH)2D. This situation would explain why, in humans, nutritional rickets and osteomalacia are commonly associated with normal or increased levels of 1,25(OH)2D (Chesney et al. 1981Citation , Eastwood et al. 1979Citation , Garabedian et al. 1983Citation ,Rasmussen et al. 1980Citation )-these are not like the low hormone levels associated with any other endocrine-deficiency disorder. A connection between lower vitamin D nutrition and vitamin D resistance helps to explain why the supposedly inactive compound 25(OH)D is more relevant in diagnosing nutritional rickets than is the active hormone 1,25(OH)2D.
If the features of improved vitamin D nutrition shown here were demonstrated for any newly synthesized compound, the compound would be classified as a noncalcemic 1,25(OH)2D analogue (Brown et al. 1989Citation , Finch et al. 1999Citation , Goff et al. 1993Citation , Koshizuka et al. 1999Citation ). Thus, we contend that 25(OH)D or a metabolite of it other than 1,25(OH)2D exists as a physiological and biologically-active noncalcemic vitamin D metabolite whose effects require further examination, particularly in relationship to studies involving the synthetic analogs of 1,25(OH)2D.
Vitamin D in defense of the human immune response.\nAdams JS, Liu PT, Chun R, Modlin RL, Hewison M.\nAnn N Y Acad Sci. 2007 Nov;1117:94-105. Epub 2007 Jul 26. Review.\nPMID: 17656563\nDOI: 10.1196/annals.1402.03
Conclusions: Healthy men seem to use 3000-5000 IU cholecalciferol/d, apparently meeting > 80% of their winter cholecalciferol need with cutaneously synthesized accumulations from solar sources during the preceding summer months. Current recommended vitamin D inputs are inadequate to maintain serum 25-hydroxycholecalciferol concentration in the absence of substantial cutaneous production of vitamin D.
Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol.
Heaney RP, Davies KM, Chen TC, Holick MF, Barger-Lux MJ.
Am J Clin Nutr. 2003 Jan;77(1):204-10. Erratum in: Am J Clin Nutr. 2003 Nov;78(5):1047.
PMID: 12499343
Dose response to vitamin D supplementation among postmenopausal African American women.
Talwar SA, Aloia JF, Pollack S, Yeh JK.
Am J Clin Nutr. 2007 Dec;86(6):1657-62.
PMID: 18065583
Correlation of symptoms with vitamin D deficiency and symptom response to cholecalciferol treatment: a randomized controlled trial.
Arvold DS, Odean MJ, Dornfeld MP, Regal RR, Arvold JG, Karwoski GC, Mast DJ, Sanford PB, Sjoberg RJ.
Endocr Pract. 2009 May-Jun;15(3):203-12.
PMID: 19364687
Conclusions: Compared with participants in the placebo group, patients in the treatment group showed mild short-term improvement in the overall fibromyalgia impact score, but did not show significant improvement in most musculoskeletal symptoms or in activities of daily living.
How much vitamin D3 do the elderly need?
Viljakainen HT, Palssa A, Kärkkäinen M, Jakobsen J, Lamberg-Allardt C.
J Am Coll Nutr. 2006 Oct;25(5):429-35.
PMID: 17031013
Conclusions: A clear dose response was noted in S-25-OHD to different doses of vitamin D3. The recommended dietary intake of 15 µg is adequate to maintain the S-25-OHD concentration around 40-55 nmol/L during winter, but if the optimal S-25-OHD is higher than that even higher vitamin D intakes are needed. Interestingly, subjects with lower vitamin D status at baseline responded more efficiently to supplementation than those with more adequate status