Is Vitamin D Supplementation Even Neccessary

[Amazoniac]

This was sent to an entity in private, might interest some of you:

- The Role of Skeletal Muscle in Maintaining Vitamin D Status in Winter

"In preliminary studies, 2 sheep grazing on pasture throughout the year had 25(OH)D concentrations in blood in the range 25–30 nmol/L [1 nmol ≈ 0.4 ng] at the end of winter, compared with the typical concentration in sheep in summer of about 50 nmol/L (4). However, in contrast to the low concentration of 0.1–0.2 μg 25(OH)D/100 g wet weight of muscle in summer, analysis of biopsies of skeletal muscle of these sheep in winter revealed that the concentration of 25(OH)D was 30 to 70 times greater at 6.8–7 μg/100 g. When these sheep were each given an oral dose of 1.25 mg 25(OH)D (at day 0), the plasma concentration predictably rose to values, 5 d later, of ∼150 nmol/L. Surprisingly, however, this elevation of vitamin D status resulted in a gradual fall in the concentration of 25(OH)D in muscle biopsies, so that after 40 d the 25(OH)D concentrations in both muscle and plasma had declined to the usual levels found in summer. It seems, therefore, that when vitamin D status improves, the ability of muscle cells to accumulate large quantities of 25(OH)D is lost (Figure 4) (4, 39)."​

- Skeletal Muscle and the Maintenance of Vitamin D Status (follow-up by the same people)

 

[Amazoniac]

- Photoimmunology: how ultraviolet radiation affects the immune system

 

[Amazoniac]

- Lipids in ultraviolet radiation-induced immune modulation

Ultraviolet (UV) radiation-mediated immune suppression is a key mechanism conferring both detrimental and beneficial impacts of sun exposure on human health. Suppression of anti-tumour responses promotes the development and progression of UV-induced skin cancers. In contrast, suppression of dysregulated immune responses facilitate the therapeutic success of phototherapy treatment for skin disorders and is postulated to be responsible for UV protection from autoimmune diseases. While some of the molecular and cellular mechanisms underlying UV-suppression of the immune system are known, a relatively unexplored area is immunomodulatory lipids. Cutaneous UV exposure changes lipids both locally in the skin, increasing platelet-activating factor (PAF) production and decreasing free triglyceride levels, and systemically reducing adipose tissue mass. There is growing recognition that bioactive lipids and lipid metabolism directly affect immune cell phenotype and function. Manipulation of immunomodulatory lipid pathways are effective strategies in modifying systemic immune responses. Indeed, the PAF pathway is a key initiator of UV-induced immune suppression and antagonism of PAF-receptors restores immune function and reduces skin cancer development in mice. This review focuses on the known effects of UV on lipids and proposes how this may in turn be involved in the modulation of the immune system.

 

[CreakyJoints]

- Lipids in ultraviolet radiation-induced immune modulation

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I am still a long way from understanding everything here, but do you suppose the speed of the effect on skin and gut microbiota with UVB exposure is perhaps quite important, compared to the presumably more circuitous routes of oral and topical vitamin D administration? Is there more of an overlap in the effects on both that way, and do they therefore work synergistically?

 

[Amazoniac]

I am still a long way from understanding everything here, but do you suppose the speed of the effect on skin and gut microbiota with UVB exposure is perhaps quite important, compared to the presumably more circuitous routes of oral and topical vitamin D administration? Is there more of an overlap in the effects on both that way, and do they therefore work synergistically?

In terms of venom D, synthesizing in the skin is more elaborate than obtaining through other means and the rate that it appears systemically probably impacts its fate. Too much at once is depleting, doesn't give time to renew the factors needed for it to work. It may signal desensitization or the need to improve elimination pathways.

I think this one was mentioned and discussed elsewhere, but I couldn't find it.
- Ultraviolet Irradiation of Skin Alters the Faecal Microbiome Independently of Vitamin D in Mice

 

[CreakyJoints]

In terms of venom D, synthesizing in the skin is more elaborate than obtaining through other means and the rate that it appears systemically probably impacts its fate. Too much at once is depleting, doesn't give time to renew the factors needed for it to work. It may signal desensitization or the need to improve elimination pathways.

I think this one was mentioned and discussed elsewhere, but I couldn't find it.
- Ultraviolet Irradiation of Skin Alters the Faecal Microbiome Independently of Vitamin D in Mice

Thank you, this is quite helpful.

 

[Dave Clark]

Two interesting studies that show how nuanced vitamin D is :

Study reveals connection between gut bacteria and vitamin D levels

Our gut microbiomes—the many bacteria, viruses and other microbes living in our digestive tracts—play important roles in our health and risk for disease in ways that are only beginning to be recognized.

medicalxpress.com

Vitamin D production after UVB exposure depends on baseline vitamin D and total cholesterol but not on skin pigmentation - PubMed

UVB radiation increases serum vitamin D level expressed as 25-hydroxyvitamin-D(3) (25(OH)D), but the influence of skin pigmentation, baseline 25(OH)D level, and total cholesterol has not been well characterized. To determine the importance of skin pigmentation, baseline 25(OH)D level, and total...

pubmed.ncbi.nlm.nih.gov

As I had always suspected, it is more than just slamming down several thousand units of oral D everyday, in fact, it has shown to even be problematic.

 

[Aegon24]

Vitamin D deficiency is often a magnesium deficiency.

Its imunomodulatory effects can be very good when it remains in the range of homeostasis of estrogen, cortisol In particular by inhibiting pgc-1a.

 

[Amazoniac]

- Does hypothyroidism augment sun-induced skin damage?

 

[Amazoniac]

- The D-lemma: narrow-band UV type B radiation versus vitamin D supplementation versus sunlight for cardiovascular and immune health

"There have been a multitude of mainly association studies suggesting that vitamin D deficiency is associated with hypertension, cardiovascular disease, and cardiovascular mortality (2). Season has a dramatic influence on cardiac mortality, and it has also been observed that serum cholesterol concentrations and blood pressure are lower during the summer than in winter in both men and women (3). Furthermore, systolic and diastolic blood pressure increases as distance from the equator increases (3). A 6-wk study in patients with chronic kidney disease who were exposed to either UVB or UVA radiation showed that not only did the UVB-irradiated patients increase their 25(OH)D concentrations by 180%, they also had a significant 6–mm Hg decrease in their systolic and diastolic blood pressures. Those exposed to UVA radiation did not show any improvement in their blood pressure nor in their blood concentrations of 25(OH)D. A follow-up study for a duration of 26 wk yielded similar results, and what was remarkable was that the improvement in blood pressure was sustained for an additional 9 mo (4). As noted by the authors, during exposure to sunlight there are innumerable photochemical and biological processes that occur in the skin. These include, among others, the production and release of nitric oxide, carbon monoxide, and β-endorphin; increased expression of the proopiomelanocortin gene, resulting in an increase in adrenocorticotropin hormone; and enhancement of collagen synthesis and wound healing, to name a few (3–5). These processes are controlled by various energies (i.e., wavelengths within the solar spectrum including UVA, UVB, and visible and infrared radiation) (4). In addition, it is well documented that solar exposure has a direct influence on the immune system, inducing immune tolerance and enhancing the production of cathelicidin to reduce infection by virulent pathogens (4–6). Therefore, the observation by Ponda et al. (1) that exposure to narrow-band UVB radiation had a different effect on gene expression in both the peripheral blood and skin compared with oral vitamin D3 was not unexpected. It was previously reported that vitamin D supplementation of 2000 IU daily to healthy adults altered the expression of 291 genes in the peripheral blood white blood cells, affecting >80 different metabolic processes (7).

When all of this is taken into consideration, one can begin to appreciate that Mother Nature never intended to have vitamin D be the panacea nutrient or hormone to treat and prevent a multitude of chronic illnesses, including cardiovascular disease, type 2 diabetes, autoimmune diseases, neurocognitive dysfunction, and deadly cancers (3–6). Instead, Mother Nature purposefully designed us with a lack of substantial body hair and an appropriate amount of skin melanin to take advantage of the plethora of beneficial photobiological processes that occur in the skin as a result of being exposed to the broad spectrum of solar radiation (spanning energies of 290 to >2500 nm) while minimizing skin damage and skin cancer. The sunshine vitamin D3 is just one of the many photochemicals and photo-byproducts produced in the skin that have important implications for overall health. The observation of Felton et al. (8) showed that adults with a skin type 2 (based on the Fitzpatrick skin-type classification) exposed to stimulated low-level United Kingdom midday sunlight 6 times/wk for 6 wk resulted in increasing their blood concentrations of 25(OH)D by 49%, while at the same time, inducing mechanisms to minimize UVB-induced DNA damage, supports the premise that you can have your cake and eat it too. Narrow-band UVB radiation can be helpful to treat several chronic skin disorders and improve vitamin D status but is not likely to provide health benefits afforded by exposure to sunlight (9). We should consider the skin as a recipient of a panoply of wavelengths that, in concert, provides the perfect symphony for good health."​

I'm sharing because the author is none other than Mike.

 

[charlie]

- The D-lemma: narrow-band UV type B radiation versus vitamin D supplementation versus sunlight for cardiovascular and immune health

"There have been a multitude of mainly association studies suggesting that vitamin D deficiency is associated with hypertension, cardiovascular disease, and cardiovascular mortality (2). Season has a dramatic influence on cardiac mortality, and it has also been observed that serum cholesterol concentrations and blood pressure are lower during the summer than in winter in both men and women (3). Furthermore, systolic and diastolic blood pressure increases as distance from the equator increases (3). A 6-wk study in patients with chronic kidney disease who were exposed to either UVB or UVA radiation showed that not only did the UVB-irradiated patients increase their 25(OH)D concentrations by 180%, they also had a significant 6–mm Hg decrease in their systolic and diastolic blood pressures. Those exposed to UVA radiation did not show any improvement in their blood pressure nor in their blood concentrations of 25(OH)D. A follow-up study for a duration of 26 wk yielded similar results, and what was remarkable was that the improvement in blood pressure was sustained for an additional 9 mo (4). As noted by the authors, during exposure to sunlight there are innumerable photochemical and biological processes that occur in the skin. These include, among others, the production and release of nitric oxide, carbon monoxide, and β-endorphin; increased expression of the proopiomelanocortin gene, resulting in an increase in adrenocorticotropin hormone; and enhancement of collagen synthesis and wound healing, to name a few (3–5). These processes are controlled by various energies (i.e., wavelengths within the solar spectrum including UVA, UVB, and visible and infrared radiation) (4). In addition, it is well documented that solar exposure has a direct influence on the immune system, inducing immune tolerance and enhancing the production of cathelicidin to reduce infection by virulent pathogens (4–6). Therefore, the observation by Ponda et al. (1) that exposure to narrow-band UVB radiation had a different effect on gene expression in both the peripheral blood and skin compared with oral vitamin D3 was not unexpected. It was previously reported that vitamin D supplementation of 2000 IU daily to healthy adults altered the expression of 291 genes in the peripheral blood white blood cells, affecting >80 different metabolic processes (7).​

​

When all of this is taken into consideration, one can begin to appreciate that Mother Nature never intended to have vitamin D be the panacea nutrient or hormone to treat and prevent a multitude of chronic illnesses, including cardiovascular disease, type 2 diabetes, autoimmune diseases, neurocognitive dysfunction, and deadly cancers (3–6). Instead, Mother Nature purposefully designed us with a lack of substantial body hair and an appropriate amount of skin melanin to take advantage of the plethora of beneficial photobiological processes that occur in the skin as a result of being exposed to the broad spectrum of solar radiation (spanning energies of 290 to >2500 nm) while minimizing skin damage and skin cancer. The sunshine vitamin D3 is just one of the many photochemicals and photo-byproducts produced in the skin that have important implications for overall health. The observation of Felton et al. (8) showed that adults with a skin type 2 (based on the Fitzpatrick skin-type classification) exposed to stimulated low-level United Kingdom midday sunlight 6 times/wk for 6 wk resulted in increasing their blood concentrations of 25(OH)D by 49%, while at the same time, inducing mechanisms to minimize UVB-induced DNA damage, supports the premise that you can have your cake and eat it too. Narrow-band UVB radiation can be helpful to treat several chronic skin disorders and improve vitamin D status but is not likely to provide health benefits afforded by exposure to sunlight (9). We should consider the skin as a recipient of a panoply of wavelengths that, in concert, provides the perfect symphony for good health."​

I'm sharing because the author is none other than Mike.

Boom. Full spectrum sunlight is where its at. I will be outside, feel free to join me.

 

[Amazoniac]

- Vitamin D deficiency exacerbates UV/endorphin and opioid addiction

 

[Dave Clark]

- Vitamin D deficiency exacerbates UV/endorphin and opioid addiction

Wondering how low dose naltrexone affects all this?

 

[Amazoniac]

Vitamin D and lumisterol novel metabolites can inhibit SARS-CoV-2 replication machinery enzymes

⬑ [14] Photoprotective properties of vitamin D and lumisterol hydroxyderivatives

- Understanding how mild skin hyperthermia influences vitamin D skin absorption and metabolism during nutritional supplementation (project presentation only)

Spoiler

"The world-wide sales of vitamin D supplements are increasing but, the vast majority of these supplements are orally administered. The oral vitamin D supplements suffer from poor compliance, gastrointestinal (GI) side-effects, the risk of overdose and poor quality (Boonen et al., 2006. J Intern Med, 259:539-52; Unson et al., 2006. Contemporary clinical trials, 27, 215-26, Wan et al., 2020), therefore there is a need to provide alternative methods of vitamin D supplementation.

King’s College London have synthesised a novel pre-vitamin D compound that can provide vitamin D supplementation using a transdermal patch. However, to achieve optimal administration there is a need to better understand the local skin metabolism. In this project the team at King’s will work with Curapel, who have developed and patented a heat patch (GB2544813), which could help to control the local metabolism of vitamin D in the skin (Kassis and Søndergaard. Arch Dermatol Res 1982; 273: 301–306). In addition, the Jones group have shown heat fluidises the outer layer of the skin, the Stratum corneum, to facilitate the absorption of hydrophobic agents such as vitamin D after application to the skin (Wood et al., Eur. J. Pharm. Biopharm. 2012. 81:642–649).

The aim of this study is to understand how mild skin hyperthermia influences vitamin D skin absorption and metabolism during nutritional supplementation with a view to using this information to develop a new approach to administer vitamin D supplementation by direct delivery into the skin."

- Is Vitamin D Supplementation Even Neccessary

Jorge, will is pre-venom product too?

 

[Braveheart]

Vitamin D deficiency is often a magnesium deficiency.

Its imunomodulatory effects can be very good when it remains in the range of homeostasis of estrogen, cortisol In particular by inhibiting pgc-1a.

Yes....just a few...

Magnesium and Vitamin D Deficiency as a Potential Cause of Immune Dysfunction, Cytokine Storm and Disseminated Intravascular Coagulation in covid-19 patients - PubMed

Magnesium and vitamin D each have the possibility of affecting the immune system and consequently the cytokine storm and coagulation cascade in COVID-19 infections. Vitamin D is important for reducing the risk of upper respiratory tract infections and plays a role in pulmonary epithelial health...

pubmed.ncbi.nlm.nih.gov

Magnesium Supplementation in Vitamin D Deficiency - PubMed

Vitamin D screening assay is readily available, but the reported lower limit of the normal range is totally inadequate for disease prevention. Based on the epidemiologic studies, ∼75% of all adults worldwide have serum 25(OH)D levels of <30 ng/mL. Because of the recent increase in global awarenes …

pubmed.ncbi.nlm.nih.gov

 

[Amazoniac]

- Is Vitamin D Supplementation Even Neccessary

- A computational model for previtamin D3 production in skin

Spoiler

- Molecular Mechanisms of UV-Induced Apoptosis and Its Effects on Skin Residential Cells: The Implication in UV-Based Phototherapy

Spoiler

 

[Amazoniac]

- Characterization of the Translocation Process of Vitamin D3 from the Skin into the Circulation

Spoiler

"[..]we found no detectable amount of preD3 present in serum samples at early times after irradiation. Therefore, it is concluded that only vitamin D3 is preferentially removed from skin into circulation, leaving behind preD3 to continue its thermal isomerization to vitamin D3."

---

"[..]previous studies demonstrated that the content of 7-DHC in rat skin was increased after repeated exposure of rats to UV irradiation (28-30). The possible physiological significance of this positive feedback regulation is to ensure that there is plenty of substrate available to photosynthesize preD3. In addition, it may be that 7-DHC acts as a natural sunscreen to reduce the harmful effects of UV-B on the skin, as hypothesized by Holick (18)."

 

[Amazoniac]

- Mobilising vitamin D from adipose tissue: The potential impact of exercise

"Vitamin D is lipophilic and early studies used radioactive isotopes to demonstrate its accumulation in adipose tissue (Rosenstreich et al. 1971; Mawer et al. 1972). Supplementing with 20 000 international units (IU) of vitamin D3 per week for 3–5 years leads to a substantial increase in vitamin D3 content in subcutaneous abdominal adipose tissue, approximately sixfold greater than placebo (Didriksen et al. 2015). The amount of 25(OH)D present in adipose explants remained correlated with serum 25(OH)D concentrations 1 year after supplementation had ceased (Martinaityte et al. 2017). Although it is worth noting that values for serum 25(OH)D and adipose tissue vitamin D3 measured in this study varied considerably between participants, which may be explained by the fourfold variation in body fat mass across the study population. There is a positive linear correlation between vitamin D3 concentrations in subcutaneous abdominal adipose tissue and serum (Blum et al. 2008b). High concentrations of vitamin D3 have been observed in adipose tissue from various sites (perirenal, pericardial, axillary and cervical) taken from humans who were not known to be supplementing with vitamin D (Lawson et al. 1986). Vitamin D storage was highly variable between adipose depots (Lawson et al. 1986), which may be driven by depot-specific differences in adipose tissue blood flow or metabolism; differences which have been identified when comparing subcutaneous abdominal adipose and gluteofemoral adipose (Manolopoulos et al. 2010). Furthermore, the relative amount of vitamin D (i.e. per gram of subcutaneous abdominal adipose tissue) is highly variable between individuals (Blum et al. 2008b; Pramyothin et al. 2011). It has recently been suggested that vitamin D accumulates in greater concentrations in omental adipose than subcutaneous abdominal adipose (Carrelli et al. 2017). However, given that the mass of subcutaneous adipose tissue is fourfold to sixfold greater than that of visceral adipose tissue (Ross et al. 2000; Merlotti et al. 2017), the absolute capacity and accumulation of vitamin D in subcutaneous adipose depots is likely to be quantitatively more important. Nonetheless, further research is needed to understand both the distribution and inter-/intra-individual variability of vitamin D accumulation across different adipose depots."

"Whilst adipose can accumulate both vitamin D3 and 25(OH)D, the limited data available suggest that the concentrations of vitamin D3 are much greater (Piccolo et al. 2013; Didriksen et al. 2015). Published values for the amount of vitamin D3 present in subcutaneous adipose tissue vary substantially, ranging from ~4 to ~500 ng/g, suggesting large individual variability and dependency on supplementation status (Didriksen et al. 2015). For an individual weighing 100 kg, with 40% body fat, this may equate to 160–20 000 ug vitamin D3, which is the equivalent to anywhere between 16 and 2000 days of the daily reference nutrient intake (RNI) of total dietary vitamin D (10 ug) for the UK population (Fig. 1). The median value for vitamin D3 in adipose of non-supplementing humans with overweight or obesity is 32 ng/g (Didriksen et al. 2015), which equates to 128 days of the RNI. Thus, adipose tissue has the potential to accumulate a substantial amount of vitamin D, especially when adipose mass is expanded (i.e. in overweight and obesity)."​

- Skeletal Muscle and the Maintenance of Vitamin D Status

 

[Apple]

Plasma klotho and vitamin D both decrease with age. Higher levels of klotho are associated with lower mortality through lowering the risk of chronic disease, so vitamin D supplementation might have favorable effects on the amount of klotho, longevity and could promote healthy aging.

Effect of vitamin D supplementation on klotho protein, antioxidant status and nitric oxide in the elderly: A randomized, double-blinded, placebo-controlled clinical trial

Vitamin D has anti-aging/wellness properties because of its ability to induce klotho, a bona fide anti-senescence protein, and suggesting that optimum…

www.sciencedirect.com

 

[Lejeboca]

"Vitamin D is lipophilic and early studies used radioactive isotopes to demonstrate its accumulation in adipose tissue (Rosenstreich et al. 1971; Mawer et al. 1972). Supplementing with 20 000 international units (IU) of vitamin D3 per week for 3–5 years leads to a substantial increase in vitamin D3 content in subcutaneous abdominal adipose tissue, approximately sixfold greater than placebo (Didriksen et al. 2015). The amount of 25(OH)D present in adipose explants remained correlated with serum 25(OH)D concentrations 1 year after supplementation had ceased (Martinaityte et al. 2017). Although it is worth noting that values for serum 25(OH)D and adipose tissue vitamin D3 measured in this study varied considerably between participants, which may be explained by the fourfold variation in body fat mass across the study population. There is a positive linear correlation between vitamin D3 concentrations in subcutaneous abdominal adipose tissue and serum (Blum et al. 2008b). High concentrations of vitamin D3 have been observed in adipose tissue from various sites (perirenal, pericardial, axillary and cervical) taken from humans who were not known to be supplementing with vitamin D (Lawson et al. 1986). Vitamin D storage was highly variable between adipose depots (Lawson et al. 1986), which may be driven by depot-specific differences in adipose tissue blood flow or metabolism; differences which have been identified when comparing subcutaneous abdominal adipose and gluteofemoral adipose (Manolopoulos et al. 2010). Furthermore, the relative amount of vitamin D (i.e. per gram of subcutaneous abdominal adipose tissue) is highly variable between individuals (Blum et al. 2008b; Pramyothin et al. 2011). It has recently been suggested that vitamin D accumulates in greater concentrations in omental adipose than subcutaneous abdominal adipose (Carrelli et al. 2017). However, given that the mass of subcutaneous adipose tissue is fourfold to sixfold greater than that of visceral adipose tissue (Ross et al. 2000; Merlotti et al. 2017), the absolute capacity and accumulation of vitamin D in subcutaneous adipose depots is likely to be quantitatively more important. Nonetheless, further research is needed to understand both the distribution and inter-/intra-individual variability of vitamin D accumulation across different adipose depots."​

​

"Whilst adipose can accumulate both vitamin D3 and 25(OH)D, the limited data available suggest that the concentrations of vitamin D3 are much greater (Piccolo et al. 2013; Didriksen et al. 2015). Published values for the amount of vitamin D3 present in subcutaneous adipose tissue vary substantially, ranging from ~4 to ~500 ng/g, suggesting large individual variability and dependency on supplementation status (Didriksen et al. 2015). For an individual weighing 100 kg, with 40% body fat, this may equate to 160–20 000 ug vitamin D3, which is the equivalent to anywhere between 16 and 2000 days of the daily reference nutrient intake (RNI) of total dietary vitamin D (10 ug) for the UK population (Fig. 1). The median value for vitamin D3 in adipose of non-supplementing humans with overweight or obesity is 32 ng/g (Didriksen et al. 2015), which equates to 128 days of the RNI. Thus, adipose tissue has the potential to accumulate a substantial amount of vitamin D, especially when adipose mass is expanded (i.e. in overweight and obesity)."​

Thanks, Amazoniac.

In the two papers you've linked, positive correlation with the exercise intensity is found in serum and muscle, respectively. The "Mobilizing vitamin D..." paper suggests that the vitamin D is released due to lipolysis: "Exercise in the fasted or the fed state leads to an approximate twofold to threefold increase in adipose tissue lipolysis (Wolfe et al. 1990; Klein et al. 1994; Enevoldsen et al. 2004) and, when stored triacylglycerol is hydrolysed, vitamin D metabolites may also be released from the lipid droplet (Fig. 3)."

Spoiler: Fig. 3

Given that lipolysis is baaa-d, I'll venture to say that the enhanced vit. D amounts in blood are to mitigate the harmful effects of lipolysis. What do you think?

To add to my point, the paper mentions that "..in vivo, as individuals with obesity display lower rates of lipolysis during exercise than lean controls (Stich et al. 2000; Mittendorfer et al. 2004). Whilst this may protect individuals with obesity from elevated circulating fatty acids (McQuaid et al. 2011), it may also contribute to sequestration of vitamin D. In support of this contention, adipose explants taken from individuals with obesity release less vitamin D when stimulated with lipolytic hormones than explants from lean controls (Di Nisio et al. 2017)." "there is a weak negative relationship between fat mass and circulating 1,25(OH)_2 D.", which is pro-inflammatory.

To sum up, keep your adipose-tissue vitamin D stores for a rainy day, do not exercise hard .