Marshall Protocol Knowledge Base - home:pathogenesis:vitamind

Vitamin D and cancer

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 20:53:53 +0000

Mistaking correlation for causation in vitamin D studies

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 20:53:53 +0000

Forms and structure of vitamin D

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 20:53:53 +0000

10.13.2018		current
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	All forms of vitamin D are secosteroids, sharing a close structural and functional resemblance to steroids. The full implications of a "vitamin" acting as a steroid has yet to be fully appreciated by many in the research community. The overlap between steroids and secosteroids is key to understanding the Marshall Pathogenesis. It explains how this "vitamin" can exert short-term palliative effects and long-term harm. Patients on the MP are advised to avoid consuming vitamin D, because of its immunomodulatory effects.		All forms of vitamin D are secosteroids, sharing a close structural and functional resemblance to steroids. The full implications of a "vitamin" acting as a steroid has yet to be fully appreciated by many in the research community. The overlap between steroids and secosteroids is key to understanding the Marshall Pathogenesis. It explains how this "vitamin" can exert short-term palliative effects and long-term harm. Patients on the MP are advised to avoid consuming vitamin D, because of its immunomodulatory effects.

-	[[http://www.answers.com/Q/Is_vitamin_d_a_steroid\|Is vitamin D a steroid?]]	+	[[https://www.answers.com/Q/Is_vitamin_d_a_steroid\|Is vitamin D a steroid?]]

	===== Summary of different forms =====		===== Summary of different forms =====
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	The levels of each of the vitamin D metabolites are affected by a complex network of feedback mechanisms involving multiple enzymes and receptors, indicating vitamin D is regulated more like a steroid than a nutrient.		The levels of each of the vitamin D metabolites are affected by a complex network of feedback mechanisms involving multiple enzymes and receptors, indicating vitamin D is regulated more like a steroid than a nutrient.

-	In the published literature, researchers sometimes distinguish between "steroid" and "secosteroid," but not always.(({{pubmed>long:10052453}})) (({{pubmed>long:12528991}}))	+	In the published literature, researchers sometimes distinguish between "steroid" and "secosteroid," but not always.(({{pmid>long:10052453}})) (({{pmid>long:12528991}}))

	This failure to discriminate is less an indication of sloppy research and more a testament to how vitamin D behaves. The vitamins D act very much like steroids, binding nuclear receptors and modulating the immune response. Not only that, there's growing evidence that vitamin D causes adverse side effects like chronic disease over the long term as do anabolic steroids and [[home:othertreatments::corticosteroids\|corticosteroids]].		This failure to discriminate is less an indication of sloppy research and more a testament to how vitamin D behaves. The vitamins D act very much like steroids, binding nuclear receptors and modulating the immune response. Not only that, there's growing evidence that vitamin D causes adverse side effects like chronic disease over the long term as do anabolic steroids and [[home:othertreatments::corticosteroids\|corticosteroids]].
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		+	{{tag>pathogenesis Science_behind_vitamin_D Simple_Explanations}}


-		+	<nodisp>
-	{{tag>Science_behind_vitamin_D Simple_Explanations}}	+
-		+
	===== Notes and comments =====		===== Notes and comments =====

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	* Legacy content		* Legacy content
	*		*
-	===== References =====	+	===== References =====</nodisp>

Latitude studies on vitamin D and disease

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 20:53:53 +0000

10.13.2018		current
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	===== Diabetes =====		===== Diabetes =====

-	Garland //et al// concluded on the basis of country-specific incidence rates of Type I diabetes that there is a correlation between a country's rate of diabetes and sun exposure.(({{pubmed>long:18548227}})) In his paper, Garland concluded that Type I diabetes could be prevented by consuming vitamin D or spending time in the noonday sun. As [[http://www.cbc.ca/technology/story/2008/07/07/strauss-vitamind.html\|described]] by CBC News's Stephen Strauss, there are several weaknesses of this study.	+	Garland //et al// concluded on the basis of country-specific incidence rates of Type I diabetes that there is a correlation between a country's rate of diabetes and sun exposure.(({{pmid>long:18548227}})) In his paper, Garland concluded that Type I diabetes could be prevented by consuming vitamin D or spending time in the noonday sun. As [[https://www.cbc.ca/technology/story/2008/07/07/strauss-vitamind.html\|described]] by CBC News's Stephen Strauss, there are several weaknesses of this study.

-	First, Garland and team generated none of their own data, but instead had taken incidence levels collected around the world and first published by Karvonen //et al// in a 2000 paper.(({{pubmed>long:11023146}})) This may be immaterial except that the original paper did not make any mention of a latitude gradient.	+	First, Garland and team generated none of their own data, but instead had taken incidence levels collected around the world and first published by Karvonen //et al// in a 2000 paper.(({{pmid>long:11023146}})) This may be immaterial except that the original paper did not make any mention of a latitude gradient.

	Those who look at the data points for the study could probably surmise why not. According to the data, the world's highest rate of Type I diabetes is in sunny Sardinia, Italy. There are other inconsistencies.		Those who look at the data points for the study could probably surmise why not. According to the data, the world's highest rate of Type I diabetes is in sunny Sardinia, Italy. There are other inconsistencies.
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	Ethnicity made a monumental difference. No place in China had a high rate, even when you travelled to Harbin — which is north of most of Mongolia.... Nonetheless, Harbin's rate was less than a quarter that of Hong Kong, which is situated more than 2,800 kilometres to the south. Not to mention that the estimated rates in the Finnish paper for Sao Paolo were roughly the same as in Tierra del Fuego, some 5,000 kilometres to the south.		Ethnicity made a monumental difference. No place in China had a high rate, even when you travelled to Harbin — which is north of most of Mongolia.... Nonetheless, Harbin's rate was less than a quarter that of Hong Kong, which is situated more than 2,800 kilometres to the south. Not to mention that the estimated rates in the Finnish paper for Sao Paolo were roughly the same as in Tierra del Fuego, some 5,000 kilometres to the south.

-	//Stephen Strauss, [[http://www.cbc.ca/technology/story/2008/07/07/strauss-vitamind.html\|	+	//Stephen Strauss, [[https://www.cbc.ca/technology/story/2008/07/07/strauss-vitamind.html\|
	Vitamin D and diabetes: An over-simplified solution to a complex problem]]//</blockquote>		Vitamin D and diabetes: An over-simplified solution to a complex problem]]//</blockquote>

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-	Looking at Karvonen's original study, it is striking to consider that the countries with the world's highest rates of Type I diabetes (in order: Finland, Sweden, Canada, and Norway) also have relatively high rates of vitamin D supplementation. One Finnish study of children born in 1966 found that between 74 and 88% of mothers reported giving their children vitamin D supplements in the form of cod liver oil, typically.(({{pubmed>long:15699498}}))	+	Looking at Karvonen's original study, it is striking to consider that the countries with the world's highest rates of Type I diabetes (in order: Finland, Sweden, Canada, and Norway) also have relatively high rates of vitamin D supplementation. One Finnish study of children born in 1966 found that between 74 and 88% of mothers reported giving their children vitamin D supplements in the form of cod liver oil, typically.(({{pmid>long:15699498}}))
	===== Cancer =====		===== Cancer =====

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	==== Australia and New Zealand vs. Northern Europe ====		==== Australia and New Zealand vs. Northern Europe ====

-	Multiple authors have cited what may be called the "Australia/New Zealand" paradox.(({{pubmed>long:18180454}})) In his 2006 review,(({{pubmed>long:16704633}})) Diffey cites "overwhelming evidence that people living in Australia and New Zealand are exposed to considerably more solar UV radiation than those living in northern Europe." The annual ambient solar UV radiation in southern Australia and New Zealand is about two to three times that in northern Europe (United Kingdom, Ireland, Scandinavia and the Baltic States), rising to more than a fourfold increase in northern Australia. Further, studies of individual exposure to sunlight demonstrate that median doses in Australia are appreciably higher than those measured in a similar cohort of subjects in England.	+	Multiple authors have cited what may be called the "Australia/New Zealand" paradox.(({{pmid>long:18180454}})) In his 2006 review,(({{pmid>long:16704633}})) Diffey cites "overwhelming evidence that people living in Australia and New Zealand are exposed to considerably more solar UV radiation than those living in northern Europe." The annual ambient solar UV radiation in southern Australia and New Zealand is about two to three times that in northern Europe (United Kingdom, Ireland, Scandinavia and the Baltic States), rising to more than a fourfold increase in northern Australia. Further, studies of individual exposure to sunlight demonstrate that median doses in Australia are appreciably higher than those measured in a similar cohort of subjects in England.

	In the review, Diffey points to epidemiological evidence, which clearly shows that the latitudinal gradient-cancer connection does not hold true at least among a large selection of countries containing large numbers of gentically related people with similar skin types, which is important for the photosynthesis of vitamin D.		In the review, Diffey points to epidemiological evidence, which clearly shows that the latitudinal gradient-cancer connection does not hold true at least among a large selection of countries containing large numbers of gentically related people with similar skin types, which is important for the photosynthesis of vitamin D.
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	<blockquote>For some cancers, there may even be a significant inverse latitude gradient. Differences in sun exposure habits and skin types can probably not explain this observation because the inverse relationship remains when we use CMM [cutaneous malignant melanoma] incidence rates as a crude measure for real UV exposures. However, taking more countries into consideration, we see that no reliable north–south gradient can be extracted. There is a large variation of the incidence rates by factors of ≈50 and 5 for prostate cancer and breast cancer, respectively. Even for countries at the same latitude, large differences are found.		<blockquote>For some cancers, there may even be a significant inverse latitude gradient. Differences in sun exposure habits and skin types can probably not explain this observation because the inverse relationship remains when we use CMM [cutaneous malignant melanoma] incidence rates as a crude measure for real UV exposures. However, taking more countries into consideration, we see that no reliable north–south gradient can be extracted. There is a large variation of the incidence rates by factors of ≈50 and 5 for prostate cancer and breast cancer, respectively. Even for countries at the same latitude, large differences are found.

-	//Moan et al.//(({{pubmed>long:8180454}}))</blockquote>	+	//Moan et al.//(({{pmid>long:8180454}}))</blockquote>
	==== United States ====		==== United States ====

-	In the case of the gradient in different rates of cancer supposedly observed in the United States. Darrell S. Rigel, M.D, president of the American Academy for Dermatology has also [[http://www.aad.org/media/background/news/Releases/The_Myths_and_Realities_of_Vitamin_D_and_Sun_Expos/\|argued consistently]] that no scientific studies exist which prove the statement that low low levels of light exposure lead to increases in cancers and other diseases:	+	In the case of the gradient in different rates of cancer supposedly observed in the United States. Darrell S. Rigel, M.D, president of the American Academy for Dermatology has also [[https://www.aad.org/media/background/news/Releases/The_Myths_and_Realities_of_Vitamin_D_and_Sun_Expos/\|argued consistently]] that no scientific studies exist which prove the statement that low low levels of light exposure lead to increases in cancers and other diseases:

	<blockquote>The claim is based on a study that finds that overall cancer rates are higher in the northeast United States, a location with lower sunlight levels than many other places in the country. Those making this claim conclude that since the Northeast has lower UV levels, this is the reason why cancer rates are higher in this region. However, several studies prove this theory is false. These include studies which show that cancer rates are low in the Northern Plains states – areas of the United States that have lower UV levels then the states in the Northeast. Furthermore, several regional studies have shown that the increased levels of cancer observed in the Northeast states are tied to levels of industrial pollutants rather than levels of UV light.		<blockquote>The claim is based on a study that finds that overall cancer rates are higher in the northeast United States, a location with lower sunlight levels than many other places in the country. Those making this claim conclude that since the Northeast has lower UV levels, this is the reason why cancer rates are higher in this region. However, several studies prove this theory is false. These include studies which show that cancer rates are low in the Northern Plains states – areas of the United States that have lower UV levels then the states in the Northeast. Furthermore, several regional studies have shown that the increased levels of cancer observed in the Northeast states are tied to levels of industrial pollutants rather than levels of UV light.
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	=====Multiple sclerosis=====		=====Multiple sclerosis=====

-	The latitude at which people spend their youth up to the age of about 15 years correlates with later risk of multiple sclerosis, with people who grow up closer to the equator having a lesser risk of disease onset.(({{pubmed>long:10871801}})) While a number of commentators have blamed vitamin D deficiency, Bains has argued that near-horizon sunshine is at fault.(({{pubmed>long:19906495}}))	+	The latitude at which people spend their youth up to the age of about 15 years correlates with later risk of multiple sclerosis, with people who grow up closer to the equator having a lesser risk of disease onset.(({{pmid>long:10871801}})) While a number of commentators have blamed vitamin D deficiency, Bains has argued that near-horizon sunshine is at fault.(({{pmid>long:19906495}}))

	A common precursor for multiple sclerosis is optic neuritis or inflammation of the optic nerve. Optic neuritis can be caused by directly looking at the Sun, something that few people willingly do, but inadvertently happens in locations far from the Equator, in which the Sun is often close to the horizon.		A common precursor for multiple sclerosis is optic neuritis or inflammation of the optic nerve. Optic neuritis can be caused by directly looking at the Sun, something that few people willingly do, but inadvertently happens in locations far from the Equator, in which the Sun is often close to the horizon.
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	<blockquote>Actually, there is no experience of causation: events do not wear their causal credentials on their faces.		<blockquote>Actually, there is no experience of causation: events do not wear their causal credentials on their faces.

-	//L.R. Karhausen// (({{pubmed>long:11080970}}))</blockquote>	+	//L.R. Karhausen// (({{pmid>long:11080970}}))</blockquote>

	Without a precise understanding of underlying disease mechanisms, researchers could just as well conclude, for example, that sunshine exposure causes teenage pregnancy.		Without a precise understanding of underlying disease mechanisms, researchers could just as well conclude, for example, that sunshine exposure causes teenage pregnancy.

-	{{:home:pathogenesis:vitamind:teenpregnancy.001.gif?nolink\|Image from American Human Development Project of the Social Science Research Council. URL: http://measureofamerica.org/maps/}}	+	{{:home:pathogenesis:vitamind:teenpregnancy.001.gif?nolink\|Image from American Human Development Project of the Social Science Research Council. URL: https://measureofamerica.org/maps/}}


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-	{{tag> Science_behind_vitamin_D Light Study_Design }}	+	{{tag> Science_behind_vitamin_D Lifestyle_modifications Light Study_Design }}

		+	<nodisp>
	===== Notes and comments =====		===== Notes and comments =====

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	<blockquote>need a new article? vitamin D production on skin		<blockquote>need a new article? vitamin D production on skin

-	Trevor talks about this here: http://www.marshallprotocol.com/view_topic.php?id=13471	+	Trevor talks about this here: https://www.marshallprotocol.com/view_topic.php?id=13471


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-	* atherosclerosis in African Americans – Vitamin D is widely used to treat patients with osteoporosis and/or low vitamin D levels based on a medically accepted normal range. This "normal" range is typically applied to all race groups, although it was established predominantly in whites. It is thought that as low vitamin D levels rise to the normal range with supplementation, protection from bone and heart disease (atherosclerosis) may increase, as well. Blacks generally have lower vitamin D levels than whites, partly because their darker skin pigmentation limits the amount of the vitamin produced by sunlight. "Despite" these lower vitamin D levels and dietary calcium ingestion, blacks naturally experience lower rates of osteoporosis and have far less calcium in their arteries. Studies further reveal that black patients with diabetes have half the rate of heart attack as whites, when provided equal access to health care. A 2010 study (explained [[http://www.sciencedaily.com/releases/2010/03/100315091259.htm\|here]]) determined the relationship between circulating vitamin D levels and arterial calcium in 340 black men and women with type 2 diabetes.(({{pubmed>long:20061416}})) The team concluded that higher circulating levels of 25-D in blacks were associated with higher levels of calcified atherosclerotic plaque.	+	* atherosclerosis in African Americans – Vitamin D is widely used to treat patients with osteoporosis and/or low vitamin D levels based on a medically accepted normal range. This "normal" range is typically applied to all race groups, although it was established predominantly in whites. It is thought that as low vitamin D levels rise to the normal range with supplementation, protection from bone and heart disease (atherosclerosis) may increase, as well. Blacks generally have lower vitamin D levels than whites, partly because their darker skin pigmentation limits the amount of the vitamin produced by sunlight. "Despite" these lower vitamin D levels and dietary calcium ingestion, blacks naturally experience lower rates of osteoporosis and have far less calcium in their arteries. Studies further reveal that black patients with diabetes have half the rate of heart attack as whites, when provided equal access to health care. A 2010 study (explained [[https://www.sciencedaily.com/releases/2010/03/100315091259.htm\|here]]) determined the relationship between circulating vitamin D levels and arterial calcium in 340 black men and women with type 2 diabetes.(({{pmid>long:20061416}})) The team concluded that higher circulating levels of 25-D in blacks were associated with higher levels of calcified atherosclerotic plaque.

	<blockquote>Serum 25(OH)D concentrations in sunny Israel.Saliba W, Rennert HS, Kershenbaum A, Rennert G		<blockquote>Serum 25(OH)D concentrations in sunny Israel.Saliba W, Rennert HS, Kershenbaum A, Rennert G
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	</blockquote>		</blockquote>

-	===== References =====	+	===== References =====</nodisp>

Immunosuppression and insufficient followup in vitamin D studies

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 20:53:53 +0000

05.26.2019		current
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	This practice is a mistake as it does not account for the long-term immunosuppressive effects of a steroid.		This practice is a mistake as it does not account for the long-term immunosuppressive effects of a steroid.
-	For example, the U-shaped relationship between vitamin D levels and long-term outcome in large cohort (({{pubmed>long:27589046}}))	+	For example, the U-shaped relationship between vitamin D levels and long-term outcome in large cohort (({{pmid>long:27589046}}))

	===== Immunosuppression by high doses of vitamin D =====		===== Immunosuppression by high doses of vitamin D =====
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	===== Short-term and long-term effects of vitamin D =====		===== Short-term and long-term effects of vitamin D =====

-	People who consume vitamin D through supplements or food are suppressing their innate immune response.(({{pubmed>long:18200565}})) In the absence of a robust immune response, fewer bacteria killed. As a consequence, inflammation declines as does the amount of toxins released into the tissues. This contributes to symptom relief and feelings of temporary well-being. Without knowing anything else, researchers might erroneously conclude that supplementing with vitamin D is therapeutic.	+	People who consume vitamin D through supplements or food are suppressing their innate immune response.(({{pmid>long:18200565}})) In the absence of a robust immune response, fewer bacteria killed. As a consequence, inflammation declines as does the amount of toxins released into the tissues. This contributes to symptom relief and feelings of temporary well-being. Without knowing anything else, researchers might erroneously conclude that supplementing with vitamin D is therapeutic.

	At a certain point, however, consuming the secosteroid starts to have an effect on those symptoms which researchers typically focus their attention. A person's pathogen load increases to the point such that it cannot be offset by a mitigated immune response. This tipping point occurs at different times for different patient groups. For someone who is young and has a robust immune response, it may take decades for chronic pathogens to escalate to the point where they become symptoms of disease. On the other hand, the time to experience a negative effect for a person who is sick with a chronic disease or elderly (and presumably has a higher bacterial load), is relatively shorter.		At a certain point, however, consuming the secosteroid starts to have an effect on those symptoms which researchers typically focus their attention. A person's pathogen load increases to the point such that it cannot be offset by a mitigated immune response. This tipping point occurs at different times for different patient groups. For someone who is young and has a robust immune response, it may take decades for chronic pathogens to escalate to the point where they become symptoms of disease. On the other hand, the time to experience a negative effect for a person who is sick with a chronic disease or elderly (and presumably has a higher bacterial load), is relatively shorter.
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	There are a number of studies, too many to review in the context of this article. Generally speaking, research noting a therapeutic effect of vitamin D tend to be short-term or in patients whose immune systems are yet to be suppressed.		There are a number of studies, too many to review in the context of this article. Generally speaking, research noting a therapeutic effect of vitamin D tend to be short-term or in patients whose immune systems are yet to be suppressed.

-	A study out of Creighton University recently received attention, because the researchers found that vitamin D might lower the incidence of colorectal cancer.(({{pubmed>long:17556697}})) The length of the observation: only four years.	+	A study out of Creighton University recently received attention, because the researchers found that vitamin D might lower the incidence of colorectal cancer.(({{pmid>long:17556697}})) The length of the observation: only four years.

-	Jacques Rossouw at the National Institutes of Health criticized the finding. His group conducted a similar study that tracked the effects of vitamin D in a larger cohort (36,282 vs. 1,179 subjects) over a longer period of time (seven vs. four years).(({{pubmed>long:19001601}}))	+	Jacques Rossouw at the National Institutes of Health criticized the finding. His group conducted a similar study that tracked the effects of vitamin D in a larger cohort (36,282 vs. 1,179 subjects) over a longer period of time (seven vs. four years).(({{pmid>long:19001601}}))

	<blockquote>In our study we found absolutely no indication of an effect of calcium or vitamin D [on cancer] — zero. And that’s over a seven-year period. It was a much larger study and a much longer study.		<blockquote>In our study we found absolutely no indication of an effect of calcium or vitamin D [on cancer] — zero. And that’s over a seven-year period. It was a much larger study and a much longer study.
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	//Jacques Rossouw,// in a comment to the press </blockquote>		//Jacques Rossouw,// in a comment to the press </blockquote>

-	A 2000 study found that five patients confined to wheelchairs with severe weakness and fatigue were able to walk after supplementing with 300,000 IU’s of vitamin D, (150 times higher than the U.S. Institute of Medicine of the National Academy of Sciences' tolerable upper intake level) over a period of six weeks. But the patients were not “cured," and no follow-up study was <del>conducted</del> published on the group. Based on what is known about vitamin D metabolism, these patients were simply feeling the effect of a temporary decrease in cytokine and toxin release that resulted after the high levels of vitamin D completely shut down their innate immune systems. In fact, one of the patients actually died in the weeks during which vitamin D was administered.(({{pubmed>long: 10789615}}))	+	A 2000 study found that five patients confined to wheelchairs with severe weakness and fatigue were able to walk after supplementing with 300,000 IU’s of vitamin D, (150 times higher than the U.S. Institute of Medicine of the National Academy of Sciences' tolerable upper intake level) over a period of six weeks. But the patients were not “cured," and no follow-up study was <del>conducted</del> published on the group. Based on what is known about vitamin D metabolism, these patients were simply feeling the effect of a temporary decrease in cytokine and toxin release that resulted after the high levels of vitamin D completely shut down their innate immune systems. In fact, one of the patients actually died in the weeks during which vitamin D was administered.(({{pmid>long: 10789615}}))


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	Those researchers, which have followed subjects who have supplemented with vitamin D over the course of decades, have found that the secosteroid does have harmful effects and especially in patients with chronic disease.		Those researchers, which have followed subjects who have supplemented with vitamin D over the course of decades, have found that the secosteroid does have harmful effects and especially in patients with chronic disease.

-	One 2004 study found a clear association between high-dose vitamin D supplementation in infancy and an increased risk of atopy, allergic rhinitis, and asthma later in life.(({{pubmed>long:15699498}})) Those subjects given higher levels of vitamin D during infancy were found to suffer from higher levels of atopy, rhinitis and asthma. However the results were not apparent until the research team checked back with them at 31 years of age.	+	One 2004 study found a clear association between high-dose vitamin D supplementation in infancy and an increased risk of atopy, allergic rhinitis, and asthma later in life.(({{pmid>long:15699498}})) Those subjects given higher levels of vitamin D during infancy were found to suffer from higher levels of atopy, rhinitis and asthma. However the results were not apparent until the research team checked back with them at 31 years of age.

-	According to another group of researchers, patients consuming vitamin D are significantly more likely to have greater volumes of brain lesions, indicating regions of damage that can increase risk of cognitive impairment, dementia, depression and death. Vitamin D intake – mean 341 IU and maximum intake 1014 IU – was the only variable that retained a significant correlation with the brain lesions when analyzed by a multivariate analysis.(({{pubmed>long:19083421}})) In this case, the negative effective could be easily documented, because the subjects were older (average age 71) and presumably had a longer period to build up their pathogenic load.	+	According to another group of researchers, patients consuming vitamin D are significantly more likely to have greater volumes of brain lesions, indicating regions of damage that can increase risk of cognitive impairment, dementia, depression and death. Vitamin D intake – mean 341 IU and maximum intake 1014 IU – was the only variable that retained a significant correlation with the brain lesions when analyzed by a multivariate analysis.(({{pmid>long:19083421}})) In this case, the negative effective could be easily documented, because the subjects were older (average age 71) and presumably had a longer period to build up their pathogenic load.

-	It is worth noting that studies of certain other classes of steroids, substances which are nearly [[home:pathogenesis:vitamind:forms\|biochemically identical to vitamin D]], have opted to focus on the long-term harm the drugs cause. One study of anabolic steroids is typical. Graham //et al// documented how rates of cardiovascular disease are significantly higher in former users.(({{pubmed>long:16488899}})) The study's authors sensibly chose to study subjects only after at least 20 years of previous or current use.	+	It is worth noting that studies of certain other classes of steroids, substances which are nearly [[home:pathogenesis:vitamind:forms\|biochemically identical to vitamin D]], have opted to focus on the long-term harm the drugs cause. One study of anabolic steroids is typical. Graham //et al// documented how rates of cardiovascular disease are significantly higher in former users.(({{pmid>long:16488899}})) The study's authors sensibly chose to study subjects only after at least 20 years of previous or current use.

-	A 2010 study found that Danish neonates with the highest measurable levels of 25-D had a two-fold elevated risk of developing schizoprhenia. The relationship was not explained by a wide range of potential confounding or interacting variables.(({{pubmed>long:20819982}})) This result is consistent with the explanation that higher rates of disease were caused by the immunosuppressive effects of heavy supplementation with vitamin D.	+	A 2010 study found that Danish neonates with the highest measurable levels of 25-D had a two-fold elevated risk of developing schizoprhenia. The relationship was not explained by a wide range of potential confounding or interacting variables.(({{pmid>long:20819982}})) This result is consistent with the explanation that higher rates of disease were caused by the immunosuppressive effects of heavy supplementation with vitamin D.

-	Corticosteroids, which have a more profound effect on the immune system as well, have a well-documented effect in increasing [[home:othertreatments::corticosteroids#side_effects_of_corticosteroid_therapy\|symptoms of disease]] if not disease itself. One study found that disease relapse was significantly higher in patients trying to ease their dose of Prednisone.(({{pubmed>long: 9118698}}))	+	Corticosteroids, which have a more profound effect on the immune system as well, have a well-documented effect in increasing [[home:othertreatments::corticosteroids#side_effects_of_corticosteroid_therapy\|symptoms of disease]] if not disease itself. One study found that disease relapse was significantly higher in patients trying to ease their dose of Prednisone.(({{pmid>long: 9118698}}))


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-	[[https://www.youtube.com/watch?v=rCs7zF-EfnM\|Dr Agus]]	+	view [[https://www.youtube.com/watch?v=rCs7zF-EfnM\|Dr Agus]]
		+
		+	===== Furthermore =====
		+
		+	Two recent publications challenge the belief that 25(OH)D levels greater than 30 ng/mL are optimal for bone health. In a randomized, placebo-controlled trial, high-dose, once-yearly vitamin D therapy increased the incidence of fractures and falls. The second study reported that high-dose vitamin D did not reduce levels of parathyroid hormone or bone resorption among adults with 25(OH)D levels less than 32 ng/mL at baseline. It is time to question whether serum 25(OH)D levels of 30 ng/mL or greater are necessary for all individuals. (({{pmid>long:21369796}}))
		+
		+
		+
		+	Blood vitamin D levels were associated with a risk of metabolic syndrome in cross-sectional studies but not in longitudinal studies. (({{pmid>long:24423309}}))
		+
		+	Evidence does not support the use of vitamin D supplementation for the prevention of cancer, respiratory infections or rheumatoid arthritis. Similarly, evidence does not support vitamin D supplementation for the treatment of multiple sclerosis and rheumatoid arthritis or for improving depression/mental well-being. Regular testing of 25-hydroxyvitamin D is generally not required, and mega-doses (≥300,000 IU) appear to increase harms. Much of the evidence is at high risk of bias, with multiple flaws, including analyses of secondary endpoints, small and underpowered studies, inconsistent results and numerous other issues. Therefore, enthusiasm for a vitamin D panacea should be tempered.(({{pmid>long:26951286}}))
		+
		+	New evidence indicates that both high and low 25(OH)D levels may be associated with increased health risks.(({{pmid>long:24600673}}))
		+
		+	Despite a few hundred systematic reviews and meta-analyses, highly convincing evidence of a clear role of vitamin D does not exist for any outcome, but associations with a selection of outcomes are probable.(({{pmid>long:24690624}}))
		+
		+
		+



	{{tag>pathogenesis Science_behind_vitamin_D Study_Design}}		{{tag>pathogenesis Science_behind_vitamin_D Study_Design}}
		+	<nodisp>
	===== Notes and comments =====		===== Notes and comments =====
	//		//
	broken link//		broken link//
-	([[http://www.mayoclinic.com/health/vitamin-d/NS_patient-vitamind#68CF0415-E7FF-0DBD-10D626475E8BCDB6\|150 times higher]]	+	([[https://www.mayoclinic.com/health/vitamin-d/NS_patient-vitamind#68CF0415-E7FF-0DBD-10D626475E8BCDB6\|150 times higher]]

	--- //Sallie Q 09.14.2016// lead section added re High Dose v.D supplementation		--- //Sallie Q 09.14.2016// lead section added re High Dose v.D supplementation
Line 97:		Line 116:


-	===== References =====	+	===== References =====</nodisp>

Diseases associated with low levels of 25-D

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 20:53:53 +0000

10.27.2018		current
Line 13:		Line 13:
	A full understanding of vitamin D metabolism supports the conclusion that elevated 1,25-D and depressed 25-D are a result rather than a cause of the inflammatory process.		A full understanding of vitamin D metabolism supports the conclusion that elevated 1,25-D and depressed 25-D are a result rather than a cause of the inflammatory process.

-	Lower than normal levels of 25-D have been independently associated both with all-cause mortality(({{pubmed>long:18695076}})) (({{pubmed>long:19953106}})) and a number of chronic inflammatory diseases. The following selection of diseases (and patient groups) have been observed to display the hallmarks of this kind of dysregulated vitamin D metabolism.	+	Lower than normal levels of 25-D have been independently associated both with all-cause mortality(({{pmid>long:18695076}})) (({{pmid>long:19953106}})) and a number of chronic inflammatory diseases. The following selection of diseases (and patient groups) have been observed to display the hallmarks of this kind of dysregulated vitamin D metabolism.


Line 20:		Line 20:


-	* acute respiratory tract infections (({{pubmed>long:17823437}}))	+	* acute respiratory tract infections (({{pmid>long:17823437}}))
-	* Addison's disease (({{pubmed>long:18463048}}))	+	* Addison's disease (({{pmid>long:18463048}}))
-	* aging skin(({{pubmed>long:20882333}}))	+	* aging skin(({{pmid>long:20882333}}))
-	* alcoholism (({{pubmed>long:11005548}}))	+	* alcoholism (({{pmid>long:11005548}}))
-	* allergic rhinitis (allergies) (({{pubmed>long:19154546}})) (({{pubmed>long:19179486}}))	+	* allergic rhinitis (allergies) (({{pmid>long:19154546}})) (({{pmid>long:19179486}}))
-	* Alzheimer's disease (({{pubmed>long:18852350}}))	+	* Alzheimer's disease (({{pmid>long:18852350}}))
-	* asthma (({{pubmed>long:19179486}}))	+	* asthma (({{pmid>long:19179486}}))
-	* cancers (({{pubmed>long:19365168}}))	+	* cancers (({{pmid>long:19365168}}))
-	* breast cancer (({{pubmed>long:19451439}}))	+	* breast cancer (({{pmid>long:19451439}}))
-	* colorectal cancer (({{pubmed>long:19392870}}))	+	* colorectal cancer (({{pmid>long:19392870}}))
-	* prostate cancer (({{pubmed>long:15663995}}))	+	* prostate cancer (({{pmid>long:15663995}}))
-	* lung cancer (({{pubmed>long:16546242}}))	+	* lung cancer (({{pmid>long:16546242}}))
-	* non-Hodgkin's lymphoma (({{pubmed>long:16546242}}))	+	* non-Hodgkin's lymphoma (({{pmid>long:16546242}}))
-	* ovarian cancer (({{pubmed>long:16546242}}))	+	* ovarian cancer (({{pmid>long:16546242}}))
-	* cardiovascular disease (({{pubmed>long:18775809}})) (({{pubmed>long:19055985}})) (({{pubmed>long:19026311}})) (({{pubmed>long:19953106}}))	+	* cardiovascular disease (({{pmid>long:18775809}})) (({{pmid>long:19055985}})) (({{pmid>long:19026311}})) (({{pmid>long:19953106}}))
-	* celiac disease (({{pubmed>long:18463048}})) (({{pubmed>long:19364687}}))	+	* celiac disease (({{pmid>long:18463048}})) (({{pmid>long:19364687}}))
-	* cerebral palsy (({{pubmed>long:17655620}}))	+	* cerebral palsy (({{pmid>long:17655620}}))
-	* chronic liver disease (({{pubmed>long:19960254}}))	+	* chronic liver disease (({{pmid>long:19960254}}))
-	* Chronic obstructive pulmonary disease (({{pubmed>long:19300892}}))	+	* Chronic obstructive pulmonary disease (({{pmid>long:19300892}}))
-	* cognitive dysfunction (({{pubmed>long:19377013}})) (({{pubmed>long:19659751}}))	+	* cognitive dysfunction (({{pmid>long:19377013}})) (({{pmid>long:19659751}}))
-	* congestive heart failure (({{pubmed>long:16819575}}))	+	* congestive heart failure (({{pmid>long:16819575}}))
-	* connective tissue-associated interstitial lung diseases(({{pubmed>long:20688927}}))	+	* connective tissue-associated interstitial lung diseases(({{pmid>long:20688927}}))
-	* Crohn's disease (({{pubmed>long:12945007}}))	+	* Crohn's disease (({{pmid>long:12945007}}))
-	* cystic fibrosis (({{pubmed>long:19208064}}))	+	* cystic fibrosis (({{pmid>long:19208064}}))
-	* depression (({{pubmed>long:19249103}})) (({{pubmed>long:19690578}})) (({{pubmed>long:11005548}}))	+	* depression (({{pmid>long:19249103}})) (({{pmid>long:19690578}})) (({{pmid>long:11005548}}))
-	* diabetes, type II (({{pubmed>long:19395331}})) (({{pubmed>long:20150902}}))	+	* diabetes, type II (({{pmid>long:19395331}})) (({{pmid>long:20150902}}))
-	* diabetes, type I (({{pubmed>long:19187735}}))	+	* diabetes, type I (({{pmid>long:19187735}}))
-	* elderly(({{pubmed>long:19174492}})) (({{pubmed>long:19158198}}))	+	* elderly(({{pmid>long:19174492}})) (({{pmid>long:19158198}}))
-	* epilepsy (({{pubmed>long:19394456}}))	+	* epilepsy (({{pmid>long:19394456}}))
-	* Graves' disease (({{pubmed>long:11403104}}))	+	* Graves' disease (({{pmid>long:11403104}}))
-	* kidney disease (({{pubmed>long:18417740}}))	+	* kidney disease (({{pmid>long:18417740}}))
-	* heart failure(({{pubmed>long:20795939}}))	+	* heart failure(({{pmid>long:20795939}}))
-	* HIV (({{pubmed>long:19108690}}))	+	* HIV (({{pmid>long:19108690}}))
-	* inflammatory bowel disease (({{pubmed>long:17079566}}))	+	* inflammatory bowel disease (({{pmid>long:17079566}}))
-	* lupus (systemic lupus erythematosus) (({{pubmed>long:18662506}})) (({{pubmed>long:20169063}}))	+	* lupus (systemic lupus erythematosus) (({{pmid>long:18662506}})) (({{pmid>long:20169063}}))
-	* metabolic syndrome((Kevin C. Maki, Martyn R. Rubin, Les G. Wong, Jamie F. McManus, Christopher D. Jensen, John W. Marshall, Andrea Lawless. [[http://www.lipidjournal.com/article/S1933-2874(09)00276-1/abstract\|Serum 25-hydroxyvitamin D is independently associated with high-density lipoprotein cholesterol and the metabolic syndrome in men and women]]/ 21 July 2009 (Article in Press DOI: 10.1016/j.jacl.2009.07.003).))	+	* metabolic syndrome((Kevin C. Maki, Martyn R. Rubin, Les G. Wong, Jamie F. McManus, Christopher D. Jensen, John W. Marshall, Andrea Lawless. [[https://www.lipidjournal.com/article/S1933-2874(09)00276-1/abstract\|Serum 25-hydroxyvitamin D is independently associated with high-density lipoprotein cholesterol and the metabolic syndrome in men and women]]/ 21 July 2009 (Article in Press DOI: 10.1016/j.jacl.2009.07.003).))
-	* multiple sclerosis (({{pubmed>long:19399382}})) (({{pubmed>long:18653736}}))	+	* multiple sclerosis (({{pmid>long:19399382}})) (({{pmid>long:18653736}}))
-	* myocardial infarction (heart attack) (({{pubmed>long:18541825}}))	+	* myocardial infarction (heart attack) (({{pmid>long:18541825}}))
-	* obesity (({{pubmed>long:19276997}})) (({{pubmed>long:18984659}})) (({{pubmed>long:20204652}}))	+	* obesity (({{pmid>long:19276997}})) (({{pmid>long:18984659}})) (({{pmid>long:20204652}}))
-	* osteoarthritis (({{pubmed>long:10323440}}))	+	* osteoarthritis (({{pmid>long:10323440}})) (({{pmid>long:29279934}}))
-	* osteoporosis and osteopenia (({{pubmed>long:18430266}}))	+	* osteoporosis and osteopenia (({{pmid>long:18430266}}))
-	* pain (myalgia) (({{pubmed>long:18697776}})) (({{pubmed>long:18346069}}))	+	* pain (myalgia) (({{pmid>long:18697776}})) (({{pmid>long:18346069}}))
-	* Parkinson's disease (({{pubmed>long:18852350}}))	+	* Parkinson's disease (({{pmid>long:18852350}}))
-	* pelvic floor disorders (({{pubmed>long:20308841}}))	+	* pelvic floor disorders (({{pmid>long:20308841}}))
-	* schizophrenia (({{pubmed>long:11005548}}))	+	* schizophrenia (({{pmid>long:11005548}}))
-	* slow psychomotor processing speed ((Lee DM, Tajar A //et al//. [[http://jnnp.bmj.com/cgi/content/abstract/80/7/722\|Association between 25-hydroxyvitamin D levels and cognitive performance in middle-aged and older European men]]. //Journal of Neurology, Neurosurgery, and Psychiatry// 2009;80:722-729.))	+	* slow psychomotor processing speed ((Lee DM, Tajar A //et al//. [[https://jnnp.bmj.com/cgi/content/abstract/80/7/722\|Association between 25-hydroxyvitamin D levels and cognitive performance in middle-aged and older European men]]. //Journal of Neurology, Neurosurgery, and Psychiatry// 2009;80:722-729.))
-	* stroke (({{pubmed>long:18635847}}))	+	* stroke (({{pmid>long:18635847}}))
-	* tuberculosis (({{pubmed>long:18776821}}))	+	* tuberculosis (({{pmid>long:18776821}}))
-	* undifferentiated connective tissue disease (({{pubmed>long:18928561}}))	+	* undifferentiated connective tissue disease (({{pmid>long:18928561}}))
-	* vaginosis(({{pubmed>long:19357214}}))	+	* vaginosis(({{pmid>long:19357214}}))

	===== Anomalies =====		===== Anomalies =====
Line 75:		Line 75:
	[{{ :home:pathogenesis:vitamind:screen_shot_2012-08-28_at_8.38.05_pm.png?350\|Both lower and higher levels of 25-D are associated with increased mortality. This 2012 study analyzed blood serum from 247,574 Danish subjects and found a reverse J-curve for mortality.}}]		[{{ :home:pathogenesis:vitamind:screen_shot_2012-08-28_at_8.38.05_pm.png?350\|Both lower and higher levels of 25-D are associated with increased mortality. This 2012 study analyzed blood serum from 247,574 Danish subjects and found a reverse J-curve for mortality.}}]

-	* mortality in the Danish population – A 2012 study of 247,574 subjects found that both lower and higher levels of 25-D were associated with an increased likelihood of mortality (right).(({{pubmed>long:22573406}}))	+	* mortality in the Danish population – A 2012 study of 247,574 subjects found that both lower and higher levels of 25-D were associated with an increased likelihood of mortality (right).(({{pmid>long:22573406}}))
-	* U-shaped relationship between vitamin D levels and long-term outcome. – In a 5 year follow-up of survivors of acute myocardial infarction patients with vitamin D<10ng/mL and >30ng/mL had higher mortality rate than those with intermediate values. (({{pubmed>long:27589046}}))	+	* U-shaped relationship between vitamin D levels and long-term outcome. – In a 5 year follow-up of survivors of acute myocardial infarction patients with vitamin D<10ng/mL and >30ng/mL had higher mortality rate than those with intermediate values. (({{pmid>long:27589046}}))
	* risk of breast cancer – In a 2011 study of nurses who were predominantly premenopausal, circulating 25-D levels were not significantly associated with breast cancer risk.		* risk of breast cancer – In a 2011 study of nurses who were predominantly premenopausal, circulating 25-D levels were not significantly associated with breast cancer risk.
-	* risk of prostate cancer – In a 2008 nested case-control study appearing in //Journal of the National Cancer Institute//, Ahn //et al.// found that patients with the lowest levels of 25-D also had the lowest risk of prostate cancer.(({{pubmed>long:18505967}}))	+	* risk of prostate cancer – In a 2008 nested case-control study appearing in //Journal of the National Cancer Institute//, Ahn //et al.// found that patients with the lowest levels of 25-D also had the lowest risk of prostate cancer.(({{pmid>long:18505967}}))
-	* risk of pancreatic cancer – Patients with the highest levels of 25-D were at greatest risk of pancreatic cancer.(({{pubmed>long:20562188}}))	+	* risk of pancreatic cancer – Patients with the highest levels of 25-D were at greatest risk of pancreatic cancer.(({{pmid>long:20562188}}))
-	* some rarer cancers(({{pubmed>long:20562188}})) – non-Hodgkin lymphoma or cancers of the endometrium, esophagus, stomach, kidney, ovary and pancreas	+	* some rarer cancers(({{pmid>long:20562188}})) – non-Hodgkin lymphoma or cancers of the endometrium, esophagus, stomach, kidney, ovary and pancreas
-	* cancer mortality – A 2010 longitudinal study found that both high and low concentrations of plasma 25(OH)D were associated with elevated risks of overall and cancer mortality, and low concentrations are associated with cardiovascular mortality.(({{pubmed>long:20720256}}))	+	* cancer mortality – A 2010 longitudinal study found that both high and low concentrations of plasma 25(OH)D were associated with elevated risks of overall and cancer mortality, and low concentrations are associated with cardiovascular mortality.(({{pmid>long:20720256}}))
-	* neonatal vitamin D status and risk of schizophrenia – Danish neonates with the highest measurable levels of 25-D had a two-fold elevated risk of developing schizoprhenia. Based on this analysis, the population-attributable fraction associated with neonatal vitamin D status was 44%. The relationship was not explained by a wide range of potential confounding or interacting variables.(({{pubmed>long:20819982}})) This study is consistent with the explanation that higher rates of disease were caused by the immunosuppressive effects of heavy supplementation with vitamin D.	+	* neonatal vitamin D status and risk of schizophrenia – Danish neonates with the highest measurable levels of 25-D had a two-fold elevated risk of developing schizoprhenia. Based on this analysis, the population-attributable fraction associated with neonatal vitamin D status was 44%. The relationship was not explained by a wide range of potential confounding or interacting variables.(({{pmid>long:20819982}})) This study is consistent with the explanation that higher rates of disease were caused by the immunosuppressive effects of heavy supplementation with vitamin D.
-	* atrial fibrillation – According to results shared at a [[http://www.telegraph.co.uk/health/healthnews/8891327/High-dose-vitamin-D-pills-can-double-heart-condition-risk.html\|2012 conference]], patients with 25-D levels above 100 nanograms per 100ml, were 2.5 times more likely to have atrial fibrillation as those with more moderate levels (41-80ng/100ml).	+	* atrial fibrillation – According to results shared at a [[https://www.telegraph.co.uk/health/healthnews/8891327/High-dose-vitamin-D-pills-can-double-heart-condition-risk.html\|2012 conference]], patients with 25-D levels above 100 nanograms per 100ml, were 2.5 times more likely to have atrial fibrillation as those with more moderate levels (41-80ng/100ml).
-	* atherosclerosis in African Americans – Vitamin D is widely used to treat patients with osteoporosis and/or low vitamin D levels based on a medically accepted normal range. This "normal" range is typically applied to all race groups, although it was established predominantly in whites. It is thought that as low vitamin D levels rise to the normal range with supplementation, protection from bone and heart disease (atherosclerosis) may increase, as well. Blacks generally have lower vitamin D levels than whites, partly because their darker skin pigmentation limits the amount of the vitamin produced by sunlight. "Despite" these lower vitamin D levels and dietary calcium ingestion, blacks naturally experience lower rates of osteoporosis and have far less calcium in their arteries. Studies further reveal that black patients with diabetes have half the rate of heart attack as whites, when provided equal access to health care. A 2010 study (explained [[http://www.sciencedaily.com/releases/2010/03/100315091259.htm\|here]]) determined the relationship between circulating vitamin D levels and arterial calcium in 340 black men and women with type 2 diabetes.(({{pubmed>long:20061416}})) The team concluded that higher circulating levels of 25-D in blacks were associated with higher levels of calcified atherosclerotic plaque.	+	* atherosclerosis in African Americans – Vitamin D is widely used to treat patients with osteoporosis and/or low vitamin D levels based on a medically accepted normal range. This "normal" range is typically applied to all race groups, although it was established predominantly in whites. It is thought that as low vitamin D levels rise to the normal range with supplementation, protection from bone and heart disease (atherosclerosis) may increase, as well. Blacks generally have lower vitamin D levels than whites, partly because their darker skin pigmentation limits the amount of the vitamin produced by sunlight. "Despite" these lower vitamin D levels and dietary calcium ingestion, blacks naturally experience lower rates of osteoporosis and have far less calcium in their arteries. Studies further reveal that black patients with diabetes have half the rate of heart attack as whites, when provided equal access to health care. A 2010 study (explained [[https://www.sciencedaily.com/releases/2010/03/100315091259.htm\|here]]) determined the relationship between circulating vitamin D levels and arterial calcium in 340 black men and women with type 2 diabetes.(({{pmid>long:20061416}})) The team concluded that higher circulating levels of 25-D in blacks were associated with higher levels of calcified atherosclerotic plaque.


	{{tag>pathogenesis Science_behind_vitamin_D}}		{{tag>pathogenesis Science_behind_vitamin_D}}

		+	<nodisp>
	===== Notes and comments =====		===== Notes and comments =====

Line 96:		Line 97:


-	===== References =====	+	===== References =====</nodisp>

Mechanisms by which bacteria affect levels of vitamin D

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 20:53:53 +0000

01.25.2019		current
Line 13:		Line 13:
	Given that the VDR is fundamentally a control system for the innate immune response, the body upregulates the Receptor's activity by increasing concentrations of 1,25-D and downregulating concentrations of 25-D.		Given that the VDR is fundamentally a control system for the innate immune response, the body upregulates the Receptor's activity by increasing concentrations of 1,25-D and downregulating concentrations of 25-D.

-	One such mechanism is the CYP27B1 pathway.(({{pubmed>long:17290304}})) When the immune system is challenged by pathogens, the body activates a protein called Protein Kinase A (PKA). PKA in turn activates CYP27B1, causing more 25-D to be converted to 1,25-D, which, of course, increases activity of the VDR.(({{pubmed>long:21124742}}))	+	One such mechanism is the CYP27B1 pathway.(({{pmid>long:17290304}})) When the immune system is challenged by pathogens, the body activates a protein called Protein Kinase A (PKA). PKA in turn activates CYP27B1, causing more 25-D to be converted to 1,25-D, which, of course, increases activity of the VDR.(({{pmid>long:21124742}}))

	<blockquote>1α-OHase [CYP27B1] expression is upregulated in macrophages in response to bacterial infection and that 1α-OHase at the site of infection provides 1,25(OH)(2)D(3) for local regulation of vitamin D responsive genes.		<blockquote>1α-OHase [CYP27B1] expression is upregulated in macrophages in response to bacterial infection and that 1α-OHase at the site of infection provides 1,25(OH)(2)D(3) for local regulation of vitamin D responsive genes.

-	//C.D. Nelson// (({{pubmed>long:21124742}}))</blockquote>	+	//C.D. Nelson// (({{pmid>long:21124742}}))</blockquote>
	===== Elevated 1,25-D for extended periods implies a partially blocked VDR =====		===== Elevated 1,25-D for extended periods implies a partially blocked VDR =====

Line 31:		Line 31:
	===== Effects of VDR blockage on CYP24A1, an enzyme regulating conversion of 25-D into 1,25-D =====		===== Effects of VDR blockage on CYP24A1, an enzyme regulating conversion of 25-D into 1,25-D =====

-	When active, the VDR transcribes CYP24A1 (sometimes referred to as CYP24), which regulates levels of 25-D and 1,25-D. CYP24A1 breaks down excess 1,25-D, ensuring that the level of 1,25-D in the body stays in the normal range.(({{pubmed>long:18200565}})) It is a sensible mechanism for controlling levels of the D metabolites.	+	When active, the VDR transcribes CYP24A1 (sometimes referred to as CYP24), which regulates levels of 25-D and 1,25-D. CYP24A1 breaks down excess 1,25-D, ensuring that the level of 1,25-D in the body stays in the normal range.(({{pmid>long:18200565}})) It is a sensible mechanism for controlling levels of the D metabolites.

	<blockquote>[The production of CYP24A1] is the best documented of the feedback control systems used by the body to limit the concentration of 1,25-D to just that amount needed for proper transcription and activation of the VDR.		<blockquote>[The production of CYP24A1] is the best documented of the feedback control systems used by the body to limit the concentration of 1,25-D to just that amount needed for proper transcription and activation of the VDR.
Line 40:		Line 40:
	===== Effects of VDR blockage on the PXR, a receptor which converts pre-vitamin D into 25-D =====		===== Effects of VDR blockage on the PXR, a receptor which converts pre-vitamin D into 25-D =====

-	When 1,25-D rises due to the processes described above, it also binds a receptor called the PXR. The PXR subsequently inhibits conversion of pre-vitamin D to 25-D, causing 25-D levels to drop via the CYP27A1 pathway.(({{pubmed>long:16207822}})) (({{pubmed>long:16691293}})) PXR has also been reported to competitively downregulate the VDR-induced expression of CYP24A1, which as we saw above, breaks down excess 1,25-D.	+	When 1,25-D rises due to the processes described above, it also binds a receptor called the PXR. The PXR subsequently inhibits conversion of pre-vitamin D to 25-D, causing 25-D levels to drop via the CYP27A1 pathway.(({{pmid>long:16207822}})) (({{pmid>long:16691293}})) PXR has also been reported to competitively downregulate the VDR-induced expression of CYP24A1, which as we saw above, breaks down excess 1,25-D.

	This mechanism works well when 1,25-D is within normal ranges. But when 1,25-D becomes extremely high, as in the case of chronic diseases, 25-D is downregulated to abnormally low levels, leading some observers to erroneously conclude that vitamin D deficiency causes disease.		This mechanism works well when 1,25-D is within normal ranges. But when 1,25-D becomes extremely high, as in the case of chronic diseases, 25-D is downregulated to abnormally low levels, leading some observers to erroneously conclude that vitamin D deficiency causes disease.
Line 46:		Line 46:
	===== Recent research =====		===== Recent research =====

-	We evaluated whether the ability of M. leprae to induce type I IFN blocks the intrinsic activation of the vitamin D pathway, representing an escape mechanism by which the bacterium evades the host response. (({{pubmed>long:30300363}}))	+	We evaluated whether the ability of M. leprae to induce type I IFN blocks the intrinsic activation of the vitamin D pathway, representing an escape mechanism by which the bacterium evades the host response. (({{pmid>long:30300363}}))
		+
		+
		+	<blockquote>Vitamin D plays a crucial role in the regulation of genes central to protection against microbe invasion, such as the induction of the expression of antimicrobial peptides (also known as host defense peptides) such as CAMP and defensin. These peptides were demonstrated to disrupt the integrity of the microbe membrane, resulting in its death (Gombart, 2009). In addition, Vitamin D regulates the immune system by managing the expression of TNFα (Golovko et al., 2005), one of the most important pro-inflammatory and pro-immune cytokines. Therefore, downregulation of the vitamin D signaling pathway by viruses, can result in decreased production of antimicrobial peptides and cytokines and as a result, to attenuation of the immune response. Several studies have previously indicated that certain viruses can inhibit the Vitamin D signal transduction.
		+	</blockquote> Our in-vitro study showed that Vitamin D does not affect the rate of HBV replication, and downregulates VDR levels in the presence of the virus, thereby attenuating vitamin D signal transduction. (({{pmid>long:30326825}}))
	===== Related publications and presentations =====		===== Related publications and presentations =====

Line 53:		Line 57:

	{{tag>pathogenesis Science_behind_vitamin_D}}		{{tag>pathogenesis Science_behind_vitamin_D}}
		+	<nodisp>
	===== Notes and comments =====		===== Notes and comments =====

-	(({{pubmed>long:000}}))	+	(({{pmid>long:000}}))

	* Legacy content		* Legacy content
Line 68:		Line 73:
	The progressive decline in kidney function and concomitant loss of renal 1α-hydroxylase (CYP27B1) in chronic kidney disease (CKD) are associated with a gradual loss of circulating 25-hydroxyvitamin D3 (25(OH)D3) and 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3). However, only the decrease in 1α,25(OH)2D3 can be explained by the decline of CYP27B1, suggesting that insufficiency of both metabolites may reflect their accelerated degradation by the key catabolic enzyme 24-hydroxylase (CYP24). To determine whether CYP24 is involved in causing vitamin D insufficiency and/or resistance to vitamin D therapy in CKD, we determined the regulation of CYP24 and CYP27B1 in normal rats and rats treated with adenine to induce CKD. As expected, CYP24 decreased whereas CYP27B1 increased when normal animals were rendered vitamin D deficient. Unexpectedly, renal CYP24 mRNA and protein expression were markedly elevated, irrespective of the vitamin D status of the rats. A significant decrease in serum 1α,25(OH)2D3 levels was found in uremic rats; however, we did not find a coincident decline in CYP27B1. Analysis in human kidney biopsies confirmed the association of elevated CYP24 with kidney disease. Thus, our findings suggest that dysregulation of CYP24 may be a significant mechanism contributing to vitamin D insufficiency and resistance to vitamin D therapy in CKD.</blockquote>		The progressive decline in kidney function and concomitant loss of renal 1α-hydroxylase (CYP27B1) in chronic kidney disease (CKD) are associated with a gradual loss of circulating 25-hydroxyvitamin D3 (25(OH)D3) and 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3). However, only the decrease in 1α,25(OH)2D3 can be explained by the decline of CYP27B1, suggesting that insufficiency of both metabolites may reflect their accelerated degradation by the key catabolic enzyme 24-hydroxylase (CYP24). To determine whether CYP24 is involved in causing vitamin D insufficiency and/or resistance to vitamin D therapy in CKD, we determined the regulation of CYP24 and CYP27B1 in normal rats and rats treated with adenine to induce CKD. As expected, CYP24 decreased whereas CYP27B1 increased when normal animals were rendered vitamin D deficient. Unexpectedly, renal CYP24 mRNA and protein expression were markedly elevated, irrespective of the vitamin D status of the rats. A significant decrease in serum 1α,25(OH)2D3 levels was found in uremic rats; however, we did not find a coincident decline in CYP27B1. Analysis in human kidney biopsies confirmed the association of elevated CYP24 with kidney disease. Thus, our findings suggest that dysregulation of CYP24 may be a significant mechanism contributing to vitamin D insufficiency and resistance to vitamin D therapy in CKD.</blockquote>

-	===== References =====	+	===== References =====</nodisp>

Metabolism of vitamin D and the Vitamin D Receptor

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 20:53:53 +0000

Bias in observational epidemiological studies

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 20:53:53 +0000

12.19.2018		current
Line 13:		Line 13:
	<blockquote>Overall, the bulk of the evidence strongly supports a protective effect of estrogens that is unlikely to be explained by confounding factors.		<blockquote>Overall, the bulk of the evidence strongly supports a protective effect of estrogens that is unlikely to be explained by confounding factors.

-	//Meir Stampfer, et al.// (({{pubmed>long:1826173}}))	+	//Meir Stampfer, et al.// (({{pmid>long:1826173}}))
	</blockquote>		</blockquote>

Line 22:		Line 22:
	[{{ :home:pathogenesis:vitamind:dyh124f1.jpeg?350\|Use of hormone replacement therapy vs. number of adverse socioeconomic factors. People with less income, less education, and less access to quality healthcare were less likely to use hormone replacement therapy.}}]		[{{ :home:pathogenesis:vitamind:dyh124f1.jpeg?350\|Use of hormone replacement therapy vs. number of adverse socioeconomic factors. People with less income, less education, and less access to quality healthcare were less likely to use hormone replacement therapy.}}]

-	<html><!-- (({{pubmed>long:15166201}})) --></html>	+	<html><!-- (({{pmid>long:15166201}})) --></html>

-	Controlled trials showed that HRT caused a small and significant increase in risk of CHD. Re-analysis of the data showed that women undertaking HRT were more likely to be from [[http://en.wikipedia.org/wiki/NRS_social_grade\|socio-economic groups ABC1]], with better than average diet and exercise regimes. The two were coincident effects of a common cause, rather than cause and effect as had been supposed.(({{pubmed>long:15166201}}))	+	Controlled trials showed that HRT caused a small and significant increase in risk of CHD. Re-analysis of the data showed that women undertaking HRT were more likely to be from [[https://en.wikipedia.org/wiki/NRS_social_grade\|socio-economic groups ABC1]], with better than average diet and exercise regimes. The two were coincident effects of a common cause, rather than cause and effect as had been supposed.(({{pmid>long:15166201}}))

-	According to [[http://www.nytimes.com/2007/09/16/magazine/16epidemiology-t.html?_r=2&ref=magazine&oref=slogin\|Gary Taubes]], “The question of how many women may have died prematurely or suffered strokes or breast cancer because they were taking a pill that their physicians had prescribed to protect them against heart disease lingers unanswered. A reasonable estimate would be tens of thousands.”	+	According to [[https://www.nytimes.com/2007/09/16/magazine/16epidemiology-t.html?_r=2&ref=magazine&oref=slogin\|Gary Taubes]], “The question of how many women may have died prematurely or suffered strokes or breast cancer because they were taking a pill that their physicians had prescribed to protect them against heart disease lingers unanswered. A reasonable estimate would be tens of thousands.”

-	One retrospective commentary, full of all the requisite browbeating, asked provocatively "Is this the death of observational epidemiology?"(({{pubmed>long:15166201}}))	+	One retrospective commentary, full of all the requisite browbeating, asked provocatively "Is this the death of observational epidemiology?"(({{pmid>long:15166201}}))


Line 39:		Line 39:
	Studies in which a cohort is self-selecting can be fraught with error, especially when the groups are substantively different. The people who take vitamin D are different than those who don't. They tend to have more money, better education, and better health care, a well-documented pattern.		Studies in which a cohort is self-selecting can be fraught with error, especially when the groups are substantively different. The people who take vitamin D are different than those who don't. They tend to have more money, better education, and better health care, a well-documented pattern.

-	One recent British study is typical.(({{pubmed>long:17344510}})) The primary purpose of the study was to measure serum levels of 25-D in middle aged white adults. The patient pool consisted of 7,437 people from the 1958 British birth cohort. Researchers stratified subjects by socioeconomic class. Socioeconomic status was assessed by using the Registrar General's occupational classification based on current or most recent occupation at age 42 and categorized as I and II (professional and managerial), III (skilled) nonmanual, III (skilled) manual, and IV and V (partly skilled and unskilled).	+	One recent British study is typical.(({{pmid>long:17344510}})) The primary purpose of the study was to measure serum levels of 25-D in middle aged white adults. The patient pool consisted of 7,437 people from the 1958 British birth cohort. Researchers stratified subjects by socioeconomic class. Socioeconomic status was assessed by using the Registrar General's occupational classification based on current or most recent occupation at age 42 and categorized as I and II (professional and managerial), III (skilled) nonmanual, III (skilled) manual, and IV and V (partly skilled and unskilled).

	According to the results, subjects in the highest socioeconomic class were almost twice as likely to take cod liver, fish oil, or other supplements containing vitamin D as those in a lower class (p < 0.0001).		According to the results, subjects in the highest socioeconomic class were almost twice as likely to take cod liver, fish oil, or other supplements containing vitamin D as those in a lower class (p < 0.0001).
Line 50:		Line 50:
	\|Unclassified \|12.2% \|		\|Unclassified \|12.2% \|

-	Even studies looking at rates of supplementation in countries where the practice is more widespread have noted this effect. In a study of the 1966 Northern Finland birth cohort, which consisted of 7,648 people, it's apparent that socioeconomic status correlates with the choice to give supplements containing vitamin D.(({{pubmed>long:15699498}}))	+	Even studies looking at rates of supplementation in countries where the practice is more widespread have noted this effect. In a study of the 1966 Northern Finland birth cohort, which consisted of 7,648 people, it's apparent that socioeconomic status correlates with the choice to give supplements containing vitamin D.(({{pmid>long:15699498}}))
	* 86% of mothers who follow health education gave their children vitamin D supplements as opposed to 79% who rarely or never did.		* 86% of mothers who follow health education gave their children vitamin D supplements as opposed to 79% who rarely or never did.
	* 88% of professional mothers gave their sons and daughters vitamin D supplements as opposed to 74% of farmers' offspring.		* 88% of professional mothers gave their sons and daughters vitamin D supplements as opposed to 74% of farmers' offspring.
	* 87% of those with more than a basic education gave the supplement as opposed to 80% who had a basic or no education.		* 87% of those with more than a basic education gave the supplement as opposed to 80% who had a basic or no education.

-	==== Press releases ====	+	==== Unreliable research, Press releases ====

-	<blockquote>Dietary supplements industry press releases issued in response to clinical research findings are characterized by 'spin' that hypes results that are favourable to supplement use and denigrates results that are not.(({{pubmed>long:24992571}}))	+	<blockquote>A systematic approach using statistical techniques to assess randomization outcomes can evaluate data integrity, in this case suggesting these RCT results may be unreliable. (({{pmid>long:27920281}}))</blockquote>
		+
		+	<blockquote>Dietary supplements industry press releases issued in response to clinical research findings are characterized by 'spin' that hypes results that are favourable to supplement use and denigrates results that are not.(({{pmid>long:24992571}}))
	</blockquote>		</blockquote>
		+
		+


	{{tag>pathogenesis Science_behind_vitamin_D}}		{{tag>pathogenesis Science_behind_vitamin_D}}
		+	<nodisp>
	===== Notes and comments =====		===== Notes and comments =====

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	*		*

-	===== References =====	+	===== References =====</nodisp>

Pregnancy and vitamin D

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 20:53:53 +0000

10.13.2018		current
Line 12:		Line 12:
	The following are some of the characteristics of 1,25-D related to pregnancy:		The following are some of the characteristics of 1,25-D related to pregnancy:

-	* The 1,25-D levels increase throughout pregnancy in healthy women.(({{pubmed>long:9368509}}))	+	* The 1,25-D levels increase throughout pregnancy in healthy women.(({{pmid>long:9368509}}))
-	* The level of 1,25-D is highest in the third trimester and falls soon after delivery in healthy women.(({{pubmed>long:6600459}}))	+	* The level of 1,25-D is highest in the third trimester and falls soon after delivery in healthy women.(({{pmid>long:6600459}}))
-	* Increased serum 1,25-D levels persist through lactation.(({{pubmed>long:494995}}))	+	* Increased serum 1,25-D levels persist through lactation.(({{pmid>long:494995}}))
	* High levels of 1,25-D during pregnancy can cause increased somnolence, fatigue and symptoms such as joint pain and breathing problems.		* High levels of 1,25-D during pregnancy can cause increased somnolence, fatigue and symptoms such as joint pain and breathing problems.
	* A healthy woman will have 1,25-D manufactured by the placenta during pregnancy, but the manufacture of 1,25-D in the kidneys will be down-regulated to compensate. The kidneys of a person with advanced Th1 disease, however, have usually lost the ability to adequately down-regulate the 1,25-D level, as there is too much 1,25-D being manufactured in the inflammation, in the eyes, and in the skin.		* A healthy woman will have 1,25-D manufactured by the placenta during pregnancy, but the manufacture of 1,25-D in the kidneys will be down-regulated to compensate. The kidneys of a person with advanced Th1 disease, however, have usually lost the ability to adequately down-regulate the 1,25-D level, as there is too much 1,25-D being manufactured in the inflammation, in the eyes, and in the skin.
Line 39:		Line 39:
	[[https://academic.oup.com/cid/article/45/9/1192/370158\| Immune Reconstitution Syndrome and Exacerbation of Infections after Pregnancy ]]		[[https://academic.oup.com/cid/article/45/9/1192/370158\| Immune Reconstitution Syndrome and Exacerbation of Infections after Pregnancy ]]

-	{{tag>Science_behind_vitamin_D}}	+	{{tag>pathogenesis Science_behind_vitamin_D}}




		+	<nodisp>
	===== Notes and comments =====		===== Notes and comments =====

Line 52:		Line 53:

	===== References =====		===== References =====
		+	</nodisp>

02.01.2020		current
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	While some randomized controlled trials have suggested that consuming vitamin D reduces rates of cancer, larger and more carefully controlled studies show no such effect.		While some randomized controlled trials have suggested that consuming vitamin D reduces rates of cancer, larger and more carefully controlled studies show no such effect.
-	Lappe et al published work, conducted over four years, that seemingly showed vitamin D might lower the incidence of colorectal cancer.(({{pubmed>long:17556697}})) The study had participants take 1,100 IU’s of vitamin D over the course of four years, a time that corresponds to the period when the short-term immunosuppressive effects of the steroid would be at its strongest.	+	Lappe et al published work, conducted over four years, that seemingly showed vitamin D might lower the incidence of colorectal cancer.(({{pmid>long:17556697}})) The study had participants take 1,100 IU’s of vitamin D over the course of four years, a time that corresponds to the period when the short-term immunosuppressive effects of the steroid would be at its strongest.

	Lappe opted to discard the data of subjects who developed cancer during the first year of the study. The rationale was that cancers during the first year would have been present but undiagnosed at entry. Of the 50 people who developed cancer during the four-year study, 13 were removed based on this premise, and only 37 cases of cancer were actually analyzed. But the 13 people who developed cancer during the first year were likely to be the study participants with the highest loads of the Th1 pathogens. They would have been the people to suffer the most from the negative impact of elevated 25-D on the immune system. If data from the 13 participants would have been included in the study, the results would have undoubtedly reflected much less of a “benefit” from vitamin D. Even the researchers admit that “their conclusion was strengthened by both the observational, substantial improvement in risk reduction when cancers occurring early in the trial were excluded.”		Lappe opted to discard the data of subjects who developed cancer during the first year of the study. The rationale was that cancers during the first year would have been present but undiagnosed at entry. Of the 50 people who developed cancer during the four-year study, 13 were removed based on this premise, and only 37 cases of cancer were actually analyzed. But the 13 people who developed cancer during the first year were likely to be the study participants with the highest loads of the Th1 pathogens. They would have been the people to suffer the most from the negative impact of elevated 25-D on the immune system. If data from the 13 participants would have been included in the study, the results would have undoubtedly reflected much less of a “benefit” from vitamin D. Even the researchers admit that “their conclusion was strengthened by both the observational, substantial improvement in risk reduction when cancers occurring early in the trial were excluded.”

-	Another problem with Lappe's study is that it did not randomize participants on the basis of the stated primary outcome of the paper.(({{pubmed>long:18326620}})) As far as epidemiological research goes, this is a no-no, and is the equivalent of "moving the goalposts." Nor did it report losses to follow-up for each intervention group separately	+	Another problem with Lappe's study is that it did not randomize participants on the basis of the stated primary outcome of the paper.(({{pmid>long:18326620}})) As far as epidemiological research goes, this is a no-no, and is the equivalent of "moving the goalposts." Nor did it report losses to follow-up for each intervention group separately

-	In a similar study looking at a larger cohort and over a longer period of time, Chlebowski //et al.// found no such effect.(({{pubmed>long:16481636}}))	+	In a similar study looking at a larger cohort and over a longer period of time, Chlebowski //et al.// found no such effect.(({{pmid>long:16481636}}))

	<blockquote>In our study we found absolutely no indication of an effect of calcium or vitamin D [on cancer] — zero. And that’s over a seven-year period. It was a much larger study and a much longer study.		<blockquote>In our study we found absolutely no indication of an effect of calcium or vitamin D [on cancer] — zero. And that’s over a seven-year period. It was a much larger study and a much longer study.

-	//Jacques Rossouw, MD,// National Institutes of Health// [[http://abcnews.go.com/Health/CancerPreventionAndTreatment/Story?id=3256349&page=1\|ABC News]]//</blockquote>	+	//Jacques Rossouw, MD,// National Institutes of Health// [[https://abcnews.go.com/Health/CancerPreventionAndTreatment/Story?id=3256349&page=1\|ABC News]]//</blockquote>

-	A second study by the Women’s Health Initiative found no reduction in risk of breast cancer among postmenopausal women supplementing with 1000 mg calcium and 440 IUs of vitamin D.(({{pubmed>long:19001601}})) Researchers at the American Cancer Society conducted a study on 68,567 postmenopausal women and found that “neither use of supplemental calcium nor vitamin D intake was associated with [breast cancer] risk.”(({{pubmed>long:16365007}})) And researchers at the Northern California Cancer Center found no association between dietary vitamin D intake during adolescence and subsequent breast cancer risk.(({{pubmed>long:10350434}}))	+	A second study by the Women’s Health Initiative found no reduction in risk of breast cancer among postmenopausal women supplementing with 1000 mg calcium and 440 IUs of vitamin D.(({{pmid>long:19001601}})) Researchers at the American Cancer Society conducted a study on 68,567 postmenopausal women and found that “neither use of supplemental calcium nor vitamin D intake was associated with [breast cancer] risk.”(({{pmid>long:16365007}})) And researchers at the Northern California Cancer Center found no association between dietary vitamin D intake during adolescence and subsequent breast cancer risk.(({{pmid>long:10350434}}))

-	A 2011 systematic review of prospective studies assessing the association of vitamin D intake with the risk of colorectal cancer that vitamin D intake increased risk of colorectal cancer,(({{pubmed>long:21876081}})) thus directly contradicting Lappe's study.	+	A 2011 systematic review of prospective studies assessing the association of vitamin D intake with the risk of colorectal cancer that vitamin D intake increased risk of colorectal cancer,(({{pmid>long:21876081}})) thus directly contradicting Lappe's study.

-	Cohort studies are no more likely to show a long-term positive effect of vitamin D intake, The Iowa Women's Health study showed vitamin D intake seemed to protect against breast cancer in the first five years after it was taken. However, the effect began to reverse between years five and ten and was completely lost after year ten, trending towards an opposing effect.(({{pubmed>long:17549593}}))	+	Cohort studies are no more likely to show a long-term positive effect of vitamin D intake, The Iowa Women's Health study showed vitamin D intake seemed to protect against breast cancer in the first five years after it was taken. However, the effect began to reverse between years five and ten and was completely lost after year ten, trending towards an opposing effect.(({{pmid>long:17549593}}))

	Longitudinal studies (those lasting decades) examining the relationship between long-term intake of vitamin D and incidence of cancer are lacking. Those that have measured incidence of various other diseases, including atopy, allergic rhinitis, and brain lesions, have found that vitamin D intake increases the rate of these diseases. There is no reason to think cancer would be substantially different.		Longitudinal studies (those lasting decades) examining the relationship between long-term intake of vitamin D and incidence of cancer are lacking. Those that have measured incidence of various other diseases, including atopy, allergic rhinitis, and brain lesions, have found that vitamin D intake increases the rate of these diseases. There is no reason to think cancer would be substantially different.
Line 49:		Line 49:
	A number of vitamin D studies point to low levels of the inactive metabolite, 25-D, as playing a causative role in the incidence of cancer. Large, well-controlled studies have not been able to verify this claim.		A number of vitamin D studies point to low levels of the inactive metabolite, 25-D, as playing a causative role in the incidence of cancer. Large, well-controlled studies have not been able to verify this claim.

-	A recent study by the National Cancer Institute - the first study to look at the relationship between measured vitamin D in the blood and subsequent total cancer deaths - failed to show an association between baseline vitamin D status and overall cancer risk in men, women, non-Hispanic whites, non-Hispanic blacks, Mexican Americans, and in persons younger than 70 or 70 years or older.(({{pubmed>long:17971526}})) The study analyzed data from 16,818 subjects.	+	A recent study by the National Cancer Institute - the first study to look at the relationship between measured vitamin D in the blood and subsequent total cancer deaths - failed to show an association between baseline vitamin D status and overall cancer risk in men, women, non-Hispanic whites, non-Hispanic blacks, Mexican Americans, and in persons younger than 70 or 70 years or older.(({{pmid>long:17971526}})) The study analyzed data from 16,818 subjects.

-	When asked by a correspondent from CBS News if vitamin D can reduce the risk of cancer, [[http://www.cbsnews.com/stories/2005/12/29/eveningnews/main1168907.shtml\|said]] the following:	+	When asked by a correspondent from CBS News if vitamin D can reduce the risk of cancer, [[https://www.cbsnews.com/stories/2005/12/29/eveningnews/main1168907.shtml\|said]] the following:

	<blockquote>I don’t believe vitamin D is the answer. I wish it was as simple as saying ‘If you take vitamin D, cancer will be cured. I don’t think it’s that simple.		<blockquote>I don’t believe vitamin D is the answer. I wish it was as simple as saying ‘If you take vitamin D, cancer will be cured. I don’t think it’s that simple.
Line 59:		Line 59:
	==== Evidence that vitamin D intake increases incidence of cancer ====		==== Evidence that vitamin D intake increases incidence of cancer ====

-	An underreported body of research shows that levels of 25-D sufficiently high enough to suggest heavy supplementation are consistent with //higher// rates of cancer. Stolzenberg-Solomon //et al// tracked a cohort of men over the course of 16 years for pancreatic cancer.(({{pubmed>long:17047087}})) They found that over this time period, high 25-D levels greater than 26 ng/ml were associated with a three-fold increased risk for the cancer. It is noteworthy that according to molecular modeling research, 26 ng/ml is near the range when 25-D significantly shuts off the Vitamin D Receptor, particularly when it is already partially blocked by bacterial proteins.	+	An underreported body of research shows that levels of 25-D sufficiently high enough to suggest heavy supplementation are consistent with //higher// rates of cancer. Stolzenberg-Solomon //et al// tracked a cohort of men over the course of 16 years for pancreatic cancer.(({{pmid>long:17047087}})) They found that over this time period, high 25-D levels greater than 26 ng/ml were associated with a three-fold increased risk for the cancer. It is noteworthy that according to molecular modeling research, 26 ng/ml is near the range when 25-D significantly shuts off the Vitamin D Receptor, particularly when it is already partially blocked by bacterial proteins.

	<blockquote>Contrary to expectations, subjects with higher prediagnostic vitamin D status had an increased pancreatic cancer risk compared with those with lower status…. Our results are intriguing and may provide clues that further the understanding of the etiology of this highly fatal cancer.		<blockquote>Contrary to expectations, subjects with higher prediagnostic vitamin D status had an increased pancreatic cancer risk compared with those with lower status…. Our results are intriguing and may provide clues that further the understanding of the etiology of this highly fatal cancer.

-	//Rachael Stolzenberg-Solomon, et al.// (({{pubmed>long:17047087}}))</blockquote>	+	//Rachael Stolzenberg-Solomon, et al.// (({{pmid>long:17047087}}))</blockquote>

-	Researchers at the Chinese Academy of Medical Sciences in China found a similar association between excessive vitamin D intake and esophageal and gastric cancers in men. Male subjects with levels of 25-D in the range of 48.7 ng/ml (which once again suggests heavy supplementation) were much more likely to develop one of the two forms of cancer.(({{pubmed>long:17551495}})) A 2011 case control study found that those in the highest 25% of vitamin D intake compared to those in the lowest 25% were significantly more likely to develop oesophageal adenocarcinoma.(({{pubmed>long:21736847}}))	+	Researchers at the Chinese Academy of Medical Sciences in China found a similar association between excessive vitamin D intake and esophageal and gastric cancers in men. Male subjects with levels of 25-D in the range of 48.7 ng/ml (which once again suggests heavy supplementation) were much more likely to develop one of the two forms of cancer.(({{pmid>long:17551495}})) A 2011 case control study found that those in the highest 25% of vitamin D intake compared to those in the lowest 25% were significantly more likely to develop oesophageal adenocarcinoma.(({{pmid>long:21736847}}))

	The following research by //Freedman DM, Looker AC, Abnet CC, Linet MS, Graubard BI// remains unpublished		The following research by //Freedman DM, Looker AC, Abnet CC, Linet MS, Graubard BI// remains unpublished
Line 74:		Line 74:
	===== Observational studies=====		===== Observational studies=====

-	One Norway-based study surveyed over 50,000 participants for their intake of dietary vitamin D and then compared those results to their later risk of cutaneous malignant melanoma. The researchers found that female subjects who consumed cod liver oil, which is high in vitamin D, were significantly more likely to later be diagnosed with melanoma.(({{pubmed>long:9178814}}))	+	One Norway-based study surveyed over 50,000 participants for their intake of dietary vitamin D and then compared those results to their later risk of cutaneous malignant melanoma. The researchers found that female subjects who consumed cod liver oil, which is high in vitamin D, were significantly more likely to later be diagnosed with melanoma.(({{pmid>long:9178814}}))

-	A 2010 study showed that multivitamin use may be correlated with increased risk of breast cancer.(({{pubmed>long:20335555}})) In 1997, 35,329 Swedish cancer-free women completed a self-administered questionnaire that solicited information on multivitamin use as well as other breast cancer risk factors. During a mean follow-up of 9.5 years, 974 women were diagnosed with incident breast cancer.	+	A 2010 study showed that multivitamin use may be correlated with increased risk of breast cancer.(({{pmid>long:20335555}})) In 1997, 35,329 Swedish cancer-free women completed a self-administered questionnaire that solicited information on multivitamin use as well as other breast cancer risk factors. During a mean follow-up of 9.5 years, 974 women were diagnosed with incident breast cancer.

	===== Patient reports =====		===== Patient reports =====
Line 86:		Line 86:
	While on MP, a "pre-cancerous" patch on my left arm changed and I was referred to a dermatologist for surgery, but he preferred to watch and wait as the possible cancer was on an arm with lymphoedema.		While on MP, a "pre-cancerous" patch on my left arm changed and I was referred to a dermatologist for surgery, but he preferred to watch and wait as the possible cancer was on an arm with lymphoedema.

-	I am glad he took pictures, as the possble cancer continued to change aand then disappeared entirely. Good old MP, when follow !	+	I am glad he took pictures, as the possible cancer continued to change and then disappeared entirely.
-	</blockquote>ed as precisely as I was doing at that time.	+
		+	Good old MP, when followed as precisely as I was doing at that time.

	//Sallie Q//		//Sallie Q//
		+	</blockquote>
	===== Read more =====		===== Read more =====

-	Clinical Utility of Measurement of Vitamin D-Binding Protein and Calculation of Bioavailable Vitamin D in Assessment of Vitamin D Status (({{pubmed>long:27834063}}))	+	Clinical Utility of Measurement of Vitamin D-Binding Protein and Calculation of Bioavailable Vitamin D in Assessment of Vitamin D Status (({{pmid>long:27834063}}))


Line 101:		Line 104:

	{{tag>pathogenesis Science_behind_vitamin_D}}		{{tag>pathogenesis Science_behind_vitamin_D}}
		+	<nodisp>
	===== Notes and comments =====		===== Notes and comments =====

-	broken link [[http://www.landesbioscience.com/journals/dermatoendocrinology/Grant(3)DE2-2.pdf\|Obituary of epidemiologist Dr. Frank Garland]]	+	broken link [[https://www.landesbioscience.com/journals/dermatoendocrinology/Grant(3)DE2-2.pdf\|Obituary of epidemiologist Dr. Frank Garland]]


Line 120:		Line 124:
	Cancer Res. 2010 Sep 16. [Epub ahead of print]		Cancer Res. 2010 Sep 16. [Epub ahead of print]

-	Serum Vitamin D and Cancer Mortality in the NHANES III Study (1988-2006).(({{pubmed>long:20847342}}))	+	Serum Vitamin D and Cancer Mortality in the NHANES III Study (1988-2006).(({{pmid>long:20847342}}))
	Freedman DM, Looker AC, Abnet CC, Linet MS, Graubard BI.		Freedman DM, Looker AC, Abnet CC, Linet MS, Graubard BI.

Line 136:		Line 140:

	J Natl Med Assoc. 2009 Dec;101(12):1310-2.		J Natl Med Assoc. 2009 Dec;101(12):1310-2.
-	Black-white differences in cancer risk and the vitamin D hypothesis.(({{pubmed>long:20070025}}))	+	Black-white differences in cancer risk and the vitamin D hypothesis.(({{pmid>long:20070025}}))
	Frost P.		Frost P.
	Comment on:		Comment on:
Line 193:		Line 197:


-	<blockquote>The evolution of light skin color: role of vitamin D disputed.(({{pubmed>long:19425095}}))	+	<blockquote>The evolution of light skin color: role of vitamin D disputed.(({{pmid>long:19425095}}))

	Robins AH.		Robins AH.
Line 256:		Line 260:
	CONCLUSION: Published literature provides little evidence to support a major role of vitamin D in preventing prostate cancer or its progression.		CONCLUSION: Published literature provides little evidence to support a major role of vitamin D in preventing prostate cancer or its progression.
	PMID: 21203822</blockquote>		PMID: 21203822</blockquote>
-	===== References =====	+	===== References =====</nodisp>

09.03.2020		current
Line 6:		Line 6:


-	Many vitamin D studies suffer from methodological errors including [[home:pathogenesis:vitamind:observational_bias\|bias inherent to using self-selected subjects]] and [[home:pathogenesis:vitamind:longterm\|insufficient followup]], but perhaps their most egregious liability comes in mistaking correlation for causation. (({{pubmed>long:27610068}}))	+	Many vitamin D studies suffer from methodological errors including [[home:pathogenesis:vitamind:observational_bias\|bias inherent to using self-selected subjects]] and [[home:pathogenesis:vitamind:longterm\|insufficient followup]], but perhaps their most egregious liability comes in mistaking correlation for causation. (({{pmid>long:27610068}}))

-	It's undisputed that a wide array of studies point to the fact that 25-hydroxyvitamin D (25-D) – typically referred to in the media as vitamin D – is low in people with numerous chronic inflammatory diseases. However, these studies fail to prove that low 25-D //causes// disease. Even so, some studies assume that doubling serum levels of 25-D would drastically reduce mortality.(({{pubmed>long:21731036}}))	+	It's undisputed that a wide array of studies point to the fact that 25-hydroxyvitamin D (25-D) – typically referred to in the media as vitamin D – is low in people with numerous chronic inflammatory diseases. However, these studies fail to prove that low 25-D //causes// disease. Even so, some studies assume that doubling serum levels of 25-D would drastically reduce mortality.(({{pmid>long:21731036}}))

	In fact, molecular science has revealed that the levels of the vitamin D metabolites through a [[home:pathogenesis:vitamind:mechanisms\|series of intricate and carefully controlled feedback pathways]], mechanisms that belie the simplistic first-order mass-action model used to guide the short-sighted vitamin studies. Also, epidemiological evidence suggests that while 25-D is low in chronic disease, 1,25-D (1,25-dihydroxyvitamin D) tends to be very high, an observation which is at odds with the theory that vitamin D deficiency causes or exacerbates disease.		In fact, molecular science has revealed that the levels of the vitamin D metabolites through a [[home:pathogenesis:vitamind:mechanisms\|series of intricate and carefully controlled feedback pathways]], mechanisms that belie the simplistic first-order mass-action model used to guide the short-sighted vitamin studies. Also, epidemiological evidence suggests that while 25-D is low in chronic disease, 1,25-D (1,25-dihydroxyvitamin D) tends to be very high, an observation which is at odds with the theory that vitamin D deficiency causes or exacerbates disease.
Line 14:		Line 14:
	<blockquote>There have been lots of observational studied showing an association between various diseases and vitamin D deficiency, but there is not any evidence yet that that is a casual relationship… it may be that vitamin D deficiency is a marker of ill health.		<blockquote>There have been lots of observational studied showing an association between various diseases and vitamin D deficiency, but there is not any evidence yet that that is a casual relationship… it may be that vitamin D deficiency is a marker of ill health.

-	//Dr. Ruth McQuillan, [[http://www.nutraingredients.com/Product-Categories/Vitamins-premixes/Scottish-islands-selected-for-new-vitamin-D-study\|University of Edinburgh]]//</blockquote>	+	//Dr. Ruth McQuillan, [[https://www.nutraingredients.com/Product-Categories/Vitamins-premixes/Scottish-islands-selected-for-new-vitamin-D-study\|University of Edinburgh]]//</blockquote>

	[{{ :home:pathogenesis:vitamind:enhanced-buzz-9201-1313871611-3.jpeg?350\|A classic mistake in correlation vs. causation. This vintage advertisement implies that children are skinny because they eat and drink sugar. In the current age of skyrocketing obesity rates, sugar probably gets more blame than it deserves, but no one would say that sugar protects against obesity.}}]		[{{ :home:pathogenesis:vitamind:enhanced-buzz-9201-1313871611-3.jpeg?350\|A classic mistake in correlation vs. causation. This vintage advertisement implies that children are skinny because they eat and drink sugar. In the current age of skyrocketing obesity rates, sugar probably gets more blame than it deserves, but no one would say that sugar protects against obesity.}}]
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	There are a number of examples where low levels of a substance are known to be associated with but not cause disease.		There are a number of examples where low levels of a substance are known to be associated with but not cause disease.
-	* Folic acid – Low levels of folic acid often lead to an increase in the amino acid homocysteine – a compound that at high levels has been linked to increased incidence of cardiovascular disease (CVD). Yet, extensive studies have revealed that giving patients with CVD folic acid supplements does not lower levels of homocysteine, and that high levels of homocysteine in patients with CVD is simply a result of the disease process.(({{pubmed>long:17309931}}))	+	* Folic acid – Low levels of folic acid often lead to an increase in the amino acid homocysteine – a compound that at high levels has been linked to increased incidence of cardiovascular disease (CVD). Yet, extensive studies have revealed that giving patients with CVD folic acid supplements does not lower levels of homocysteine, and that high levels of homocysteine in patients with CVD is simply a result of the disease process.(({{pmid>long:17309931}}))
-	* Estradiol – In a recent study, both low and high serum levels of estradiol (a type of sex hormone), compared with mid-range levels, are significantly and independently associated with increased all-cause mortality in men with chronic systolic heart failure.(({{pubmed>long:19436016}})) Yet, lead author Dr. Ewa Jankowska would quickly dismiss the idea that supplementation with estradiol reduces the risk of heart failure.	+	* Estradiol – In a recent study, both low and high serum levels of estradiol (a type of sex hormone), compared with mid-range levels, are significantly and independently associated with increased all-cause mortality in men with chronic systolic heart failure.(({{pmid>long:19436016}})) Yet, lead author Dr. Ewa Jankowska would quickly dismiss the idea that supplementation with estradiol reduces the risk of heart failure.

	<blockquote>Of course, the study does not suggest that low and high estradiol concentrations themselves were the cause of increased mortality.		<blockquote>Of course, the study does not suggest that low and high estradiol concentrations themselves were the cause of increased mortality.
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-	Even among those who support widespread supplementation with vitamin D on the basis of the "deficiency" studies, there is wide acknowledgement that the understanding of vitamin D metabolism is “imprecise.”(({{pubmed>long:17867374}}))	+	Even among those who support widespread supplementation with vitamin D on the basis of the "deficiency" studies, there is wide acknowledgement that the understanding of vitamin D metabolism is “imprecise.”(({{pmid>long:17867374}}))

-	Causation should never be assumed to be self-evident.(({{pubmed>long:11080970}})) Rigorous analysis is required, especially for a system as complicated as vitamin D metabolism.	+	Causation should never be assumed to be self-evident.(({{pmid>long:11080970}})) Rigorous analysis is required, especially for a system as complicated as vitamin D metabolism.

	<blockquote>Actually, there is no experience of causation: events do not wear their causal credentials on their faces.		<blockquote>Actually, there is no experience of causation: events do not wear their causal credentials on their faces.

-	//L.R. Karhausen// (({{pubmed>long:11080970}}))</blockquote>	+	//L.R. Karhausen// (({{pmid>long:11080970}}))</blockquote>

-	In the absence of an understanding grounded in molecular and clinical evidence, the comprehension of how vitamin D affects disease becomes "black box epidemiology." (({{pubmed>long:11080970}}))	+	In the absence of an understanding grounded in molecular and clinical evidence, the comprehension of how vitamin D affects disease becomes "black box epidemiology." (({{pmid>long:11080970}}))


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	* sunshine exposure causes teenage pregnancy		* sunshine exposure causes teenage pregnancy

-	{{:home:pathogenesis:vitamind:teenpregnancy.001.gif\|Image from American Human Development Project of the Social Science Research Council. URL: http://measureofamerica.org/maps/}}	+	{{:home:pathogenesis:vitamind:teenpregnancy.001.gif\|Image from American Human Development Project of the Social Science Research Council. URL: https://measureofamerica.org/maps/}}


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	The practice of failing to measure 1,25-D is pervasive: the NIH continues to accept studies and a number of journals continue to publish papers.		The practice of failing to measure 1,25-D is pervasive: the NIH continues to accept studies and a number of journals continue to publish papers.

-	Further, mistaking 1,25-D for other forms is more common than one might think. A 2011 study actually gave "cholecalciferol" but called it elsewhere "1,25-dihydroxyvitamin-D."(({{pubmed>long:22004229}}))	+	Further, mistaking 1,25-D for other forms is more common than one might think. A 2011 study actually gave "cholecalciferol" but called it elsewhere "1,25-dihydroxyvitamin-D."(({{pmid>long:22004229}}))

	One of the reasons that 1,25-D isn't measured may be that it is harder to test. But another reason may be that a high 1,25-D is inconsistent with reports of vitamin D "deficiency." How can patients be said to be "deficient" in vitamin D when one of its metabolites, 1,25-D, is often several standard deviations greater than normal?		One of the reasons that 1,25-D isn't measured may be that it is harder to test. But another reason may be that a high 1,25-D is inconsistent with reports of vitamin D "deficiency." How can patients be said to be "deficient" in vitamin D when one of its metabolites, 1,25-D, is often several standard deviations greater than normal?
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	{{tag>pathogenesis Science_behind_vitamin_D Study_Design}}		{{tag>pathogenesis Science_behind_vitamin_D Study_Design}}

		+	[[https://jamanetwork.com/journals/jama/article-abstract/2667071\|Association Between Calcium or Vitamin D Supplementation and Fracture Incidence in Community-Dwelling Older Adults
		+	]]



		+	<nodisp>
	===== Notes and comments =====		===== Notes and comments =====

-	broken link [[http://www.theheart.org/article/971237.do\|Heartwire]]	+	broken link [[https://www.theheart.org/article/971237.do\|Heartwire]]

	* Jigsaw suggests:		* Jigsaw suggests:
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	Last edited on 18 Jul 2013 04:46 pm by Jigsaw		Last edited on 18 Jul 2013 04:46 pm by Jigsaw

-	===== References =====	+	===== References =====</nodisp>