Is Vitamin D Supplementation Even Neccessary

[Dave Clark]

It's not what Ray Peat thinks though. His email to me:
"A deficiency of vitamin D can greatly increase the susceptibility to colds and other infections; have you been using a supplement of it? Because of the lack of sunshine in Oregon from fall to spring, I’m using about 20,000 IU of vitamin D per day on my skin."

Sorry if I am repeating this question on the thread, but if Ray is using 20,000 i.u. of vitamin D on the skin, how much does he feel of that dose will be absorbed, and can we say then that whatever that is, an oral equivalent would be equally good to use?

 

[Sourdoughbanana]

If you need to bring the levels this high to feel better, you might not be addressing the cause of the issue. It can be a Netherlands deficiency. What about the other tests related to vitamin D?

I did not "bring them up". I spent a lot of time outside this summer, pop two pills a week of D3*K2 (10,000iu & 250mcg per pill) year round. I don't have any issues. Only wondering whether higher IS better or not. I could supplement less though.

 

[Cirion]

Ah, I was referring specifically to oral ingestion. I had not considered the possibility of trying topical administration, that could make a difference, since I could see how that could more closely replicate the effect of sunlight on the skin. I can not comment on the efficacy of that as I have not tried it before.

Did he say what product he is using? If that does really make a difference I'd be tempted to give it a try myself.

 

[Braveheart]

It's not what Ray Peat thinks though. His email to me:
"A deficiency of vitamin D can greatly increase the susceptibility to colds and other infections; have you been using a supplement of it? Because of the lack of sunshine in Oregon from fall to spring, I’m using about 20,000 IU of vitamin D per day on my skin."

of which how much is absorbed?

 

[dreamcatcher]

Sorry if I am repeating this question on the thread, but if Ray is using 20,000 i.u. of vitamin D on the skin, how much does he feel of that dose will be absorbed, and can we say then that whatever that is, an oral equivalent would be equally good to use?

Hi Dave, he said that if it doesn't cause sensitivities, oral supplementation is good. I don't know the absorption rate, you might like to ask Haidut about that

 

[dreamcatcher]

of which how much is absorbed?

I don't know tbh, you might like to ask some guru here:)

 

[charlie]

of which how much is absorbed?

Around 20%.

 

[haidut]

This article was posted on Zeus' Calcirol thread. It's worth reading everything.

Inflammation and vitamin D: the infection connection

"In a healthy individual, the complex interplay between innate and adaptive immunity cooperates to mount an appropriate response to infection through regulation of the vitamin D endocrine system [140]. The immune system detects and responds to the presence of intracellular bacteria by producing more 1,25(OH)2D to activate the VDR and express the crucial endogenous AMPs which enable the innate immune system to target intracellular pathogens [141]. Renal production of 1,25(OH)2D is tightly self-regulated, with the end product down-regulating its own further production. In contrast, extra-renal tissues (e.g., uterine decidua and placenta, colon, breast, prostate, spleen, bone, keratinocytes, melanoma and synovial cells, pulmonary monocytes and macrophages, etc.) which produce 1,25(OH)2D are regulated by cytokines (e.g., interferon-gamma), lipopolysaccharide, nitric oxide and intracellular VDBP, which activate the enzyme CYP27B1 to stimulate conversion of 25(OH)D to 1,25(OH)2D [142]. This extra-renal production of 1,25(OH)2D in tissues infected with intracellular bacteria can result in an excess in production of 1,25(OH)2D which may contribute to depletion and low levels of 25(OH)D [143] (Fig. 4)."

"Because extra-renal production of 1,25(OH)2D is primarily dependent on the availability of 25(OH)D [144], supplementation with vitamin D to increase 25(OH)D may promote the production of 1,25(OH)2D in non-renal tissues that are sites of intracellular infection and result in hypervitaminosis-D. Sunlight appears to play a part in this process and many patients with autoimmune disease report sun sensitivity."

"We hypothesize that when nucleated cells are parasitized by intracellular bacteria, extra-renal production of 1,25(OH)2D increases, the kidneys lose control of 1,25(OH)2D production, and pro-hormone 25(OH)D decreases due to rapid conversion to 1,25(OH)2D. The following mechanisms are thought to be responsible (Fig. 5):

- Inflammatory cytokines [but not Diokines] activate CYP27B1, an enzyme that causes more 25(OH)D to be converted to 1,25(OH)2D [146].
- The microbial-repressed VDR cannot transcribe CYP24A1 (formerly 24-hydroxylase), an enzyme that breaks down excess 1,25(OH)2D [147].
- Excess 1,25(OH)2D binds the PXR (pregnane X receptor), to inhibit conversion of vitamin D3 to 25(OH)D so 25(OH)D is down-regulated [148].
- 1,25(OH)2D inhibits the hepatic synthesis of 25(OH)D [149]."​

"Thus, low 25(OH)D may be a consequence of the inflammatory process. More studies are concluding that suboptimal circulating levels of vitamin D appear to be caused by the disease process. Waldronn et al. [150] found serum 25(OH)D was decreased following an acute inflammatory insult (i.e., orthopedic surgery) and concluded that hypovitaminosis-D may be the consequence rather than cause of chronic inflammatory diseases. Ferder et al. [151] state, “…there may be a relationship between inflammatory processes induced by chronic overstimulation of the renin angiotensin system (RAS) and the worldwide vitamin D deficiency. In fact, the pandemic of vitamin D deficiency could be the other face of increased RAS activity, which could potentially cause a lower activity or lower levels of Vitamin D.”"

"Measuring both 25(OH)D and 1,25(OH)2D (and PTH, calcium, phosphate when indicated) as clinical markers in chronic disease is more likely to provide a true picture of vitamin D status, than measuring 25(OH)D alone [155, 156] (Table 1). Measuring 1,25(OH)2D should be considered in patients with low 25(OH)D, abnormal laboratory results (especially inflammatory markers), a diagnosis of autoimmune disease or other chronic inflammatory illness, or signs of chronic systemic inflammation. For example, elevated 1,25(OH)2D may serve as a marker of Crohn’s disease [52]. The 1,25(OH)2D test is a delicate assay which is only done in specialized laboratories. False low results have been observed due to apparent sample mishandling; freezing for transport is advised to prevent sample degradation due to agitation. A high result is always accurate."

The evidence so far points to low vitamin D levels being both - a result and cause of inflammation, forming a nasty feedback mechanism similar to cortisol/estrogen. I repeatedly said on various threads that in order to know if low vitamin D is truly a deficiency or something else is going on the tests always need to include at a minimum the following biomarkers all tested together: cholecalciferol, 25-OH-D (calcidiol), 1,25-OH-D (calcitriol), 24,25-OH-D, PTH, serum calcium, phosphorus, and prolactin.
If the low vitamin D levels (most doctors typically only test 25-OH-D) are due to inflammatory reaction somewhere, then low 25-OH-D will typically be accompanied by elevated 1,25-OH-D (calcitriol), and possibly 24,25-OH-D as well as prolactina, and PTH will typially be towards bottom end of normal or even low. If the low 25-OH-D are due to plain old deficiency, 1,25-OH-D will be normal or low, prolactin will be normal or low, PTH will be towards the upper limit of normal or even above, LDL will be high, and serum calcium may be elevated. There are many other possible combinations due to various other issues, but this should be a good enough combo of biomarkers to give your doctor a run for his/her money and determine if you truly have vitamin D deficiency or something else is going on.

 

[Braveheart]

Around 20%.

You say 20%...Clacirol supposedly absorbed around 50%...just found this out after long time taking for fact that one drop was 1000iu...when really its more like two drops...is there a post somewhere that gives the absorption of all IdesLabs supps?...I feel this whole vagueness about absorption could cause problems for some?

 

[Amazoniac]

I did not click the link because from your quotes because I thought it was well over my head, but after opening it, I see that I can understand some points.

Thanks @Amazoniac. I was still on the fence about vitamin D. That study reinforces my position that vitamin D is not a vitamin at all.

What I keep seeing is that it plays a significant role in calcium metabolism and that it can be a marker for chronic inflammation. I see also that cholesterol is mentioned as a precursor to skin production of 25(OH)D:

"Bogh et al. [22] measured the baseline serum 25(OH)D and total cholesterol levels of 182 fair-skinned and dark-skinned subjects; and studied the effect of UV radiation on their serum 25(OH)D levels. They found the amount of serum 25(OH)D produced was determined by the amount of cholesterol in the skin, not on skin pigmentation."

Since cholesterol has had such a bad rap, it's not surprising that people would now be deficient in 25(OH)D.

"Ten to 15 min of sunlight or daylight exposure to a small area of skin (e.g., the forearm or face, etc.) twice a week, without sunscreen, supplies all the vitamin D necessary for health [27]."

That's a sketch. What they consider to be enough are the official requirements, but this is not optimal.
However, having plenty of calcium in the diet can make up for less vit D.

Now please picture myself doing robot voice and gestures as you go through these:
- Cow's milk has on average 50 IU of vit D per liter.
- One liter of milk weights close to a kg.
- A calf can consume 10 liters a day ("plateau of 9 to 10 kg [of milk consumption] until weaning").
So daily sun exposure + 500 IU is enough to turn a calf into a monster.

 

[Amazoniac]

I did not "bring them up". I spent a lot of time outside this summer, pop two pills a week of D3*K2 (10,000iu & 250mcg per pill) year round. I don't have any issues. Only wondering whether higher IS better or not. I could supplement less though.

3000 IU/d of supplementation is a lot if you already have plenty of sun exposure. If it makes no difference, I would consider stopping it (especially if you're not monitoring with the tests mentioned in the article or by Zeus).

 

[Dave Clark]

Around 20%.

Thanks. So, approximately, and I know this will differ from each individual, 20,000 i.u. would give you about 4,000 i.u. That is close to the dose most people use to get their blood levels up to around 50 to 60 ng/l (?) . I may try this, but I noticed that for me, sun exposure does not raise my levels as good as oral dosing, and I wonder if topical may have the same problems. However, sunlight and topical may have other factors that are beneficial. So, in the end I see myself doing all three.

 

[Forsythia]

It is criminal to continue to call this a vitamin, when the actual, factual, description of what we are talking about is a HORMONE that is manufactured in the skin in response to sunlight.

Vitamin D can be confusing. What we get from the sun and from D3 supplements is cholecalciferol or D3. Cholecalciferol is called Vitamin D but it is NOT the active hormone that is also called Vitamin D. The active hormone Vitamin D is calcitriol.

Cholecalciferol has to be processed by the body, through the kidneys, into the active hormone calcitriol. Unfortunately both cholecalciferol and calcitriol are both known as "Vitamin D".

The sun does not produce the hormone Vitamin D (it produces cholecalciferol). Supplements are not hormone Vitamin D (they are cholecalciferol).

Cholecalciferol is a precursor to the active hormone Vitamin D, calcitriol.

Unfortunately, Vitamin D was named by scientists before they understood the process so many people think that Vitamin D supplements are "hormones".

 

[rei]

looking at the vitamin D family as steroidal/hormonal is much more correct than looking at it like vitamins that ultimately get turned into the hormone calcitriol.

 

[Amazoniac]

For those that were curious but not enough to click on the links:

- Biological Effects of Sunlight, Ultraviolet Radiation, Visible Light, Infrared Radiation and Vitamin D for Health

"There is an inverse relationship between wavelength and energy. Lower wavelengths of radiation have higher energy. When human skin is exposed to sunlight it would be reasonable to conclude that the highest energy radiation i.e. UVB radiation would penetrate more deeply into the skin than lower energy photons such as UVA and visible radiation. However the skin contains a variety of macromolecules including RNA, DNA and proteins that efficiently absorb UVB photons and therefore almost all of the UVB photons are absorbed by the macromolecules in the epidermis. These macromolecules are less efficient in absorbing UVA radiation and as a result UVA radiation penetrates through the epidermis into the dermis. Very little visible and infrared radiation is absorbed by the epidermis or dermis and thus can penetrate deep into the body cavity bathing internal organs (Figure 2A). In response to exposure to sunlight, skin responds by increasing the amount of the upper dead layer, the stratum corneum, which act like mirrors and reflect and refract UVA and UVB radiation. The UVA and UVB radiation that penetrates through the epidermis reaching the epidermal-dermal junction are absorbed by the melanocytes inducing them to produce melanin (Figure 2B). The melanin is packaged into melanosomes that are released into the epidermis where they settle over the nuclei of the epidermal cells acting as an umbrella to absorb the UVB and UVA radiation so that they do not enter the cell. Absorption of UVA radiation in the epidermis and dermis can cause the formation of free radicals which can damage proteins, DNA and RNA in the cells (3). Besides being an extremely efficient sunscreen, melanin, also acts as an antioxidant and free radical scavenger, thereby reducing free radical damage to the cells (4)."

"Melanoma being the most deadly skin cancer is often found on the least sun-exposed areas." [Read Raj below]

"Many tissues and cells in the body including macrophages, brain, breast, prostate, colon and skin, to name a few, have the capacity to convert 25(OH)D to 1,25(OH)2D (29, 30). These cells also have a vitamin D receptor (VDR) and once formed in the cell 1,25(OH)2D interacts with its nuclear receptor to unlock genetic information that controls numerous metabolic processes including DNA repair, antioxidant activity and regulating cellular proliferation and differentiation (Figure 4) (31, 32)."

"Our circadian rhythm is controlled by blue light being absorbed by photoreceptors in the eye resulting in a decrease in melatonin production (36). For some people the decrease in the intensity of sunlight affected by seasonal changes prevents the suppression of melatonin and as a result the person wants to sleep and becomes listless and depressed. Bright-light therapy with 10,000 lumens for 30 min to 1 h in the morning can help suppress melatonin production in the pineal gland, thereby relieving many of the symptoms associated with SAD (37, 38)."

"although most reference laboratories report the normal range to be 20-100 ng/ml, the preferred healthful range is 30-60 ng/ml"
Therefore 45 ng/ml is a reasonable aim.

"Autocrine metabolism of 25(OH)D; when a macrophage or monocyte is stimulated through its toll-like receptor 2/1 (TLR2/1) by an infectious agent such as Mycobacterium tuberculosis or its lipopolysaccharide, the signal upregulates the expression of VDR and 1-OHase. A 25(OH)D level of 30 ng/ml or higher provides adequate substrate for 1-OHase to convert 25(OH)D to 1,25(OH)2D in mitochondria. 1,25(OH)2D travels to the nucleus, where it increases the expression of cathelicidin, a peptide capable of promoting innate immunity and inducing the destruction of infectious agents such as M. tuberculosis. It is also likely that the 1,25(OH)2D produced in monocytes or macrophages is released to act locally on activated T lymphocytes, which regulate cytokine synthesis, and activated B lymphocytes, which regulate immunoglobulin synthesis."

"When the 25(OH)D level is approximately 30 ng/ml, the risk of many common cancers is reduced."

"It is believed that the local production of 1,25(OH)2D in the breast, colon, prostate, and other tissues regulates a variety of genes that control proliferation, including p21 and p27, as well as genes that inhibit angiogenesis and induce differentiation and apoptosis. Once 1,25(OH)2D completes the task of maintaining normal cellular proliferation and differentiation, it induces expression of the enzyme 24-OHase, which enhances the catabolism of 1,25(OH)2D to the biologically inert calcitroic acid. Thus, locally produced (autocrine) 1,25(OH)2D does not enter the circulation and has no influence on calcium metabolism. The parathyroid glands have 1-OHase activity, and the local production of 1,25(OH)2D inhibits the expression and synthesis of parathyroid hormone. The 1,25(OH)2D produced in the kidney enters the circulation and can down-regulate renin production in the kidney and stimulate insulin secretion in the beta islet cells of the pancreas."

"It is also known that the skin has the ability to produce nitric oxide (NO) a known vasodilator (41). When 24 healthy volunteers were exposed to 2 standard erythemal doses of UVA radiation their blood pressure substantially decreased. Further studies revealed that UVA radiation of the forearm increased blood flow independent of NO synthase (NOS) activity. It was observed that the UVA irradiation enhanced the release of cutaneous NO stores (56)."

"Exposure to UVB radiation causes the release of carbon monoxide from hemoglobin. Carbon monoxide can cause vasodilation (57). There is also evidence that during sun exposure that substance P and calcitonin gene-related peptide are also produced in the skin. Both of these are known vasodilators (Figure 3) (58)."

"In a mouse model, naturally prone to developing type 1 diabetes, treatment with 1,25(OH)2D3 throughout their life reduced their risk of developing type 1 diabetes by more than 90% (64). A study in Finland revealed that infants during the first year of life in the 1960s who had received 2,000 IU of vitamin D3 daily for the first year of life reduced their risk of developing type 1 diabetes later in life by 88% (65)."

"In a mouse model for multiple sclerosis it was found that exposure to UVB radiation was more effective than 1,25(OH)2D3 in reducing signs of experimental autoimmune encephalitis (66)."

"Although there is strong evidence to support that improvement in vitamin D status in early life may decreased risk for many autoimmune diseases, there are likely additional benefits from exposure to ultraviolet radiation. One potential benefit may be due to the increased expression of the proopiomelanocortin (POMC) gene that not only results in the production of beta-endorphin, but also ACTH (adrenocorticotropin hormone) that increases the adrenal glands’ production of cortisol, a known modulator of the immune system (67)."

"The efficacy of red, blue and near-infrared light treatments have been evaluated for wound healing, reduction in fine lines, wrinkles and improving dermal collagen density (Figure 1). In one study ultrasonography of skin samples before and after 30 treatments of red light and energizing light technology revealed substantial improvements in the dermal collagen matrix with increased thickness. Follow-up clinical photography revealed improvement changes in wrinkles and skin roughness (70)."

"In 1915 it was reported that indoor workers had an 8-times higher risk of dying of cancer compared to outdoor workers (71)."

"[..]1,000 IUs vitamin D daily reduced the risk of colorectal cancer by as much as 50%."

"A study of women in Canada revealed that women who had the most sun exposure between the ages of 10-19 years of age had a 69% reduced risk of developing breast cancer later in life compared to women who had the least sun exposure during the same period of time (84)."

"the exact mechanisms by which sunlight helps reduce risk for developing many deadly cancers is not known"

"To maintain a serum 25(OH)D in a healthy range three approaches are suggested. Ingesting foods that naturally contain or are fortified with vitamin D can help provide some of the vitamin D requirement. Sensible sun exposure during the spring and summer and fall will improve vitamin D status. Because so many factors influence sun induced vitamin D3 synthesis an app, dminder.info, was developed to provide guidance for sensible sun exposure and reducing risk for sun burning. To guarantee vitamin D sufficiency a vitamin D supplement should also be used on a daily basis. For children 1,000 IUs and for adults 2,000 IUs daily will maintain blood levels of 25(OH)D above 30 ng/mL. For those who are obese they may require at least 2-3 times more to satisfy their requirement."​

- How UV Light Touches the Brain and Endocrine System Through Skin, and Why

"The biologically highly active UV spectra have played a fundamental role in the origin of life on Earth when simple organic molecules harnessed its energy and converted it into high-energy chemical bonds to generate molecular complexity (15–17), perhaps initiating self-organization patterns (18) (Fig. 1). In this context, it is important to mention that energy of UV is comparable to energy of covalent bonds. For instance, the carbonyl n→pi* transition (l = 280 nm) demands energy of ;4 eV (i.e., ;400 kJ/mol). It means that any electron excitement of a molecule with UV is enough to generate or break a covalent bond. In a biological system, it is also a supplemental way to support the cell with energy, while in the beginning of biogenesis—perhaps an important or even the only way."

"[..]most of biologically relevant chromophores such as compounds with a benzene ring including aromatic amino acids, biogenic amines, or proteins containing corresponding amino acids, pyrimidines, and purines with their derivatives alone or in nucleic acids, trans-urocanic acid (UCA), quinones, melatonin, indoles, melanin monomers, polymers and precursors, unsaturated lipids and 7-dehydrocholesterol as examples, absorb UVC and UVB, with surprisingly high absorption spectra in the UVC range (1, 10, 12, 13, 17, 20, 21, 23, 24, 27–29)."

"[..]UVB absorption by chromophores with their structural transformation to yield biologically relevant effects are of great importance (1, 13, 27, 30). In contrast, UVA, although it is weakly absorbed by DNA and by limited cellular chromophores (including NADH, reduced form of NADP, riboflavin, porphyrins), has the phenotypic effects that are mainly secondary to oxidative changes in the cells generated by reactive oxygen species (13, 23, 27). Another example is generation of nitric oxide (NO) from nitrosoglutathione (31) and photoreactivity of nitroxyl NO2 (32)."

"As it relates to VIS [visible light], its main retinal chromophore, in conjunction with opsin, is involved in phototransduction necessary for the vision and/or regulation of circadian rhythm (13). The flavins and pterines harvest shorter wavelengths of VIS and in conjunction with cryptochromes are involved in the photoreception and phototransduction and may affect circadian rhythm (13). Photogeneration of NO from nitrosoglutathione may contribute to the overall homeostasis of the organism, as NO, depending on the dose and the microenvironment, may act as a parahormonal regulator or neuromodulator/ neurotransmitter, or a factor of oxidative/nitrosative stress (33). Concerning light-driven circadian rhythm, it can include induction of protective mechanisms necessary to counteract UV-induced damages during exposure to daylight, and for restoration of UV-disturbed homeostasis during night."

"Because the initial recognition of the skin as the neuroendocrine organ involved in local stress responses that have systemic implications (8, 34), a substantial evidence has accumulated documenting the intracutaneous use of the same mediators and signal transduction pathways as the ones operating in the central neuroendocrine system [reviewed in (1, 4, 34–42)]."

". Doing It Every Day(soap) Is An "Endocrine Disrupter. "​

"The skin immune system communicates with this diffuse neuroendocrine system in a bidirectional fashion using the same neuroendocrine messengers, cytokines, pakpikokines, and cognate receptors, presumably to protect the local skin homeostasis against external stressors (1, 4, 8, 37). Release of soluble neuro-endocrine-immune factors into the circulation can exert systemic, endocrine, and CNS effects, as is impressively illustrated by UV radiation (UVR)–induced b-endorphin (1, 65–67) and CRH (66, 68) releases from the skin, whereas immune cells that have been UV stimulated in the skin can act as cellular “second messengers” of the cutaneous neuro-endocrineimmune system to impact on global organismal homeostasis (Fig. 2)."

"NO and its donors (nitrosothiols) represent important hormone-like regulators of skin homeostasis; at the same time, NO is a mediator of the immunological, melanogenic, and neurologic effects of UV (69, 70). NO may be produced in both enzymatic and nonenzymatic fashion. There are three types of NO synthases encoded in various loci (71), and expressed in various skin cells according to the skin status (normal vs inflamed) (72) and the predominant phase of hair follicle cycling (73, 74). When produced in high amounts, NO itself becomes a nonspecific proinflammatory effector, and an important effector of oxidative/nitrosative stress (e.g., by generation of peroxynitrite) (75)."

"NO may affect melanogenesis in both normal and malignant melanocytes (76, 77) and it potently regulates local blood flow in a paracrine manner (70). These NO-related effects strongly depend on UV. Importantly, blood-borne nitrosothiols such as nitrosoglutathione nonenzymatically release high amounts of NO upon action of UVA and short-wave VIS (31, 78). Thus, nitrosothiols serve as transient NO storage molecules and NO transport vehicles to distant body sites, executing the endocrine way of NO action. Under physiological conditions, Cu,Zn-dependent superoxide dismutase may reversely reduce NO to the nitroxyl anion NO2 (79). The latter is a chromophore for UV, and primarily undergoes phototransition to the singlet nitroxyl ¹NO- isoelectronic with singlet oxygen ¹O2 (80)."

"Although the importance of psychological factors in dermatology has long been recognized (81–83), psychodermatology as a field has recently witnessed a renaissance (84–87), not the least through improved understanding of how perceived (psychoemotional) stress aggravates or triggers skin pathology (e.g., via the induction of neurogenic inflammation) (1, 5, 37, 38, 88–94). This growing body of knowledge is complemented by more recent insights into nonclassical skin sensory activities that encompass the sensing of defined biological (95–97) and physicochemical insults/stimuli, such as olfactory receptors or TRP mediated signals, VIS, and UV, which have been considered in skin physiology only relatively recently (1, 98–100)."

"[..]it is known that the skin generates electrical fields under conditions of wound healing and that, vice versa, electrical stimulation can promote both wound healing and the induction of neural differentiation markers (108)."

"[..]only recently it has been demonstrated that UV can simultaneously stimulate all elements of the cHPA [peripheral] including glucosteroidogenesis (66, 131, 136, 143). This stimulation is dependent on wavelength with the shortest spectrum UVC having the strongest effect, followed by UVB, whereas UVA has no or minor effects restricted to increases of CRH and b-endorphin peptides (131, 136)."

"Importantly, the exposure of shaved back skin of C57BL/6 mice to UVB significantly stimulates cHPA axis activity already 12 and 24 hours after irradiation (66). Moreover,UVB enhances skin and plasma levels of CRH, urocortin, b-endorphin, ACTH, and corticosterone levels, along with simultaneous stimulation of CRH gene and protein expression in the paraventricular nucleus of the hypothalamus and of MC2R, StAR (steroidogenic acute regulatory protein), and CYP11B1 genes in adrenals. Because hypophysectomy abolishes UVB stimulation of plasma, but not of skin corticosterone levels, and has no effect on UVB stimulation of CRH and urocortin, this documents that the regulation of body homeostasis by UVB through the cHPA axis requires an intact pituitary for systemic effects."

"This systemic stimulation of POMC peptides and corticosteroidogenesis by UVB provides a plausible endocrine mechanistic explanation of the well-known phenomenon of systemic immunosuppression by UVB (144), which was traditionally thought to be secondary to changes in the keratinocyte cytokine signaling milieu and a result of immunosuppressive T-cell activities (14, 144, 145). These systemic immunosuppressive effects appear to be independent from the UVB-induced production of vitamin D (145, 146). As a consequence, stimulation of the local and systemic HPA axes or their individual elements (POMC signaling and steroidogenesis), which encompass both chemical mediators, and stimulation of cognate receptors must play an important but long neglected role in intracutaneous or systemic immunosuppression."

"[..]even eye-transmitted systemic neuroendocrine effects, at least to some extent, can be regulated by cutaneous structures that impact the ocular transmission of UVB energy."

"In this context, one should not forget that UVB energy can be absorbed by lobular, fornical-orbital, and tarsal conjunctiva and by adjacent connective tissue as well as posterior and intermarginal cutaneous elements of the eyelid, all of which represent integumental structures (98)."

"Interestingly, irradiation of the ear also enhances POMC-derived a-MSH blood levels (147–149), consistent with UVB activation of central POMC activity through the skin (66–68). Our own data also indicate involvement of neural signal transmission from the skin to the CNS with partial deviation from classical HPA paradigms, as documented by the rapid stimulation of brain and plasma CRH, b-endorphin, ACTH, and corticosterone levels 30 and/or 90 minutes after UVB exposure, with hypophysectomy having no effect on UVB-induced increases of systemic corticosterone (68). In summary, UVR can thus regulate entire or selected elements of the cHPA axis through neural and humoral mechanisms that are wavelength-dependent and defined by anatomical structures sensing UV energy."

"Recently, the hypothesis that UV can even regulate internal organ functions through the brain or spinal cord reflexes (8) has received experimental support (67, 68)."

"The UVB reception in the skin not only activated central neuroendocrine pathways, but also induced rapid systemic immunosuppressive effects, which showed an extended duration, as illustrated by inhibition of Th1 and Th2 activities in the spleen 30 and/or 90 minutes after UVB exposure that lasted for at least 24 hours (68). The concomitant rapid stimulation of systemic CRH, ACTH, b-endorphin, and corticosterone, accompanied by rapid immunosuppressive effects on splenocytes appeared to be independent of the cHPA axis (68)."

"The Hiramoto group (147–157) has also shown that exposure of the eye to the UV not only activates central (pituitary) POMC-signaling system in a wavelength-dependent manner (UVB vs UVA) that uses NO signaling, but also has distinct functional effects on internal organs and the skin depending on times postradiation varying substantially between 6 hours (151, 152), several days (149, 153), and 20 weeks (157) after UVR-exposure. These authors showed stimulation of cutaneous melanocytes by UVB-induced a-MSH (147, 149), downregulation of cutaneous Langerhans cells by UVA (151), deterioration of dextran sodium sulfate-induced ulcerative colitis by UVB and its improvement by UVA (150), and amelioration of atopic dermatitis by UVA (156). Moreover, they reported amelioration of colon carcinoma induced by azoxymethane and dextran sodium sulfate through UVA stimulation of b-endorphin and methionine-enkephalin (157) and modulation of mucosal intestinal functions by UVA (153)."

[. . . Brewing Wikipedia . . .]

Brewed: "Met-enkephalin is a potent agonist of the δ-opioid receptor, and to a lesser extent the μ-opioid receptor, with little to no effect on the κ-opioid receptor. It is through these receptors that met-enkephalin produces its opioid effects, such as analgesia and antidepressant-like effects."​

"The proposed mechanism for these UV-induced effects involves activation of the hypothalamic-pituitary (147–149, 151) or HPA axis (152)."

"Interestingly, repeated UVB exposure of the skin can negatively affect hippocampal neurogenesis and synaptic plasticity along with HPA axis activation (158)."

"The UVB stimulated b-endorphin levels in the skin (66, 131, 143), plasma (65–68), and brain (66–68) can be linked to the phenomenon of “UVB addiction” (65, 159, 160) as well as to nociceptive and other behavioral effects (1, 65, 67)." "UVB can stimulate b-endorphin production not only in the skin (66, 131, 143), but also in the brain shortly (68) or after longer time periods post exposure (66, 67) identifies an exciting area for future research into how light “touches” the brain."

"UVA also stimulates b-endorphin in the skin (131) and colon with concomitant increases of methionine-enkephalin and attenuation of colonic carcinogenesis (157). This not only documents that UVA can exert an opioidogenic effect (1, 41) but also that this may have selected beneficial health effects (157). Concerning enkephalins, it has been demonstrated that UVB can stimulate proenkephalin gene expression in skin cells in a dose- and time-dependent manner (44)."

"[..]melanocytes and keratinocytes show distinctive responses to UVR (201), and different spectra of light have different effects on free radical formation and lipid composition in the skin (202)."​

- Beneficial effects of UV radiation other than via vitamin D production

"Although UVA- and UVB-induced pigmentations are visually identical, only UVB-pigmentation results in a protection which is as large as corresponding to a factor of about 2 to 3 against DNA photodamage and erythema.11,35,36 This protection is equivalent to using a sunscreen with a sun protection factor (SPF) of 2 to 3.4"

As commented elsewhere, people think that sunscreens with a factor of 60 is very different than 30, but since it's a fraction of protection, you realize that this is not true.

Sunscreen - Wikipedia

"SPF 15" means that 1⁄15 of the burning radiation reaches the skin through the recommended thickness of sunscreen.

Therefore most of the difference is when you're working with low factors:

1/2 : 50%
1/4*: 25%
1/15: 7%
1/30: 3%
1/60: 2%

*This is the claimed factor for coconut oil. Reduction to 25% is a lot.​

"UVA photons excite endogenous chromophores (photosensitizers) in human skin which lead to generation of reactive oxygen and nitrogen species that can cause damage by themselves or enhance the damaging effect of UVB. UVA can cause immunosuppresion in human skin. A number of recent studies demonstrate that UVA radiation can provide immunoprotection and also inhibit UVB-induced immunosuppression through modulation of various cytokines and enzymes, such as expression of heme oxygenase-1 (HO-1).40 UVA exposure increases expression of HO-1 that mediates antioxidant, anti-inflammatory, antiapoptotic and anti-proliferative effects, and protects cells and tissues against oxidative stress and tissue injury.40,41"

"[..]only one study has demonstrated increased β-endorphin levels in blood after UV exposure of healthy volunteers59 while three other studies have not found increased levels of β-endorphin.60–62 At the same time even anxiety associated with the needles used for blood sampling could affect endorphin levels.62 Other indirect evidences also suggest that endorphins are released to blood. It has been demonstrated that frequent tanners almost always choose sunbed emitting UV radiation.54 In another study was shown that the use of the opioid antagonist naltrexone, used for treatment of opioid dependence, reduced UV preference and even induced withdrawal symptoms in frequent tanners.63 Chronical and frequent exposure to UV radiation may result in a tanning addiction and in a pattern of behavior similar to other types of substance-related disorder.3,64–66"

"Sunbathing or tanning beds seem to have a potential to reduce pain in patients with fibromyalgia.54 Patients with the chronic pain condition fibromyalgia have reported a greater short-term decrease in pain after exposure to UV compared with non-UV radiation exposure.54"

"UVA radiation penetrates more deeply into the skin than UVB, and reaches not only epidermis, but also dermis with blood vessels affecting dermal dendritic cells, dermal fibroblasts, endothelial cells, mast cells, and granulocytes.80 UVA radiation is absorbed by pyridine nucleotides (NAD and NADP), riboflavins, porphyrins, pteridines, cobalamins and bilirubin.80 Porphyrins and riboflavins are photosensitizers."

"The ability of UVA radiation to cause skin erythema is approximately 10^3 to 10^4 times lower than that of UVB. As UVA-1 is even less erythematogenic than broadband UVA, much higher doses of UVA-1 can be tolerated by the patients. UVA-1 phototherapy works mainly through induction of apoptosis of skin infiltrating T cells, T-cell depletion and induction of collagenase-1 expression in human dermal fibroblast.40,81"

​

"Traditionally, broadband UVB phototherapy has been used to treat psoriasis, which is an inflammatory skin disease, characterized by keratinocyte hyperproliferation with 1–2% prevalence in the general population. However, now more often narrowband UVB or monochromatic UVB are used for the clearance of psoriasis. Narrow-band UVB clears psoriasis faster and produces longer remissions than broadband UVB.74,77 Action spectra for UV-induced erythema, DNA damage, photoimmunesuppression, squamous cell carcinoma and vitamin D synthesis are very similar, all in the UVB spectral region of 280–310 nm.38 Narrowband UVB do not contain the most erythemogenic and carcinogenic wavelengths."

Ray Peat

RP: The process of psoriasis is an accelerated cell division which is probably caused by the over-hydration and possibly lack of the right balance of estrogen, progesterone and thyroid and maybe a deficiency of Vitamin A which is the restraining influence.

SM: Or vitamin D, right?

RP: Yeah, both vitamin D and A can restrain the rate of multiplication. And besides having a very fast cell division in psoriasis, it divides quickly few times and then prematurely ages and collapses into the flaky, corny, dry condition. And urea has been demonstrated to delay or prevent that premature hardening process by governing the expression of the genes, so that the senility producing proteins aren’t produced so early. And keeping the cell in a vital state longer and delaying the – both the replication and the premature aging.

"Skin exposed to UVB and UVA is more resistant to primary irritants, which may indicate the improvement of skin barrier functions.30,93,94 Such an improvement is not due to epidermal hyperplasia, which does not appear after UVA exposure, and neither is it due to increase in lipids in the stratum corneum as has been believed earlier.30,93,94"

"No mechanism other than vitamin D production has been proposed to explain the effects of UVB exposure on reducing these disease risk.96 A growing amount of molecular data demonstrates the involvement of vitamin D in cell proliferation, differentiation, apoptosis, angiogenesis, immune and inflammatory responses.97,98"

Yeet!
"It is possible that the reported protective effect of sunlight on the mentioned types of cancer and other diseases are not mediated only through vitamin D but also through other and as yet unknown mechanisms.110,119,120 A few years ago Becklund et al.120 demonstrated that vitamin D supplementation is less efficient than UV radiation in suppressing multiple sclerosis in animals. Lukas et al.121 found in a multicenter case-control study that multiple sclerosis risk decreased with increasing serum 25(OH)D levels, measured at the time of the first demyelinating events, and with increasing UV exposure, estimated by questionnaires or by the degree of actinic damage. Lukas et al.121 suggested that sun exposure and vitamin D status may play independent roles for development of central nervous system demyelination. A recent population-based case-control from Sweden122 suggested that UVR exposure may also exert a protective effect against developing multiple sclerosis via other pathways than those involving vitamin D. The role of UV and vitamin D should be evaluated in clinical trials for multiple sclerosis prevention."

Sun exposure and vitamin D are independent risk factors for CNS demyelination​

"African Americans at higher latitudes have a higher rate of vitamin D deficiency than Caucasians have.119,123,124 However, Caucasians have about two times higher rates of multiple sclerosis than African Americans have.119 (At the same time, the course of disease is more aggressive among African Americans.)125 Therefore, the involvement of additional mechanisms, rather than only vitamin D synthesis, has been proposed.119,120 Other mediators than vitamin D that are induced by UV radiation may be more important for UV-mediated immunomodulation and may be involved in the prevention and progression of immunopathological diseases (psoriasis, multiple sclerosis and asthma), non-immunopathological diseases (cancer) and during infection.119,126,127 It is clear that exposure to UV radiation is an important environmental interference with immune functions126,127 which may play important roles in prevention, initiation or progression of several diseases."

"A few years ago it was demonstrated that nitric oxide (NO'), a gaseous free radical, is non-enzymatically induced in skin by UVA.128–130 However, UVA-induced NO' and its influence on human physiology and pathophysiology are not so well studied as the influence of NO' produced enzymatically by NO synthases.131 NO' is able to diffuse rapidly across cell membranes, and, depending on the conditions, is able to diffuse more than several hundred microns. The biological half-life of NO' is in the range from 1 ms to 2 sec, depending on superoxide (O2'-), antioxidants and oxygen concentrations.2 The biological effects of NO' are mediated through the reaction of NO' with a number of targets, such as haem groups, cysteine residues and iron and zinc clusters. This wide range of targets for NO' helps to explain the multiple roles it plays, including vasodilatation, immune defense, neurotransmission, regulation of cell death (apoptosis) and cell motility. Due to the importance of NO', abnormal regulation of the concentration of UV-induced NO' may affect a number of important biological processes."

"The rapid release of NO' following UVA exposure suggests the existence of latent stores. It is well known that part of the endogenously produced NO' is converted into nitrite (NO2-), nitrate or nitrosothiols. Earlier it was thought that these compounds are inert end products of endogenous NO' metabolism. In 2003 Rodriguez et al.132 demonstrated that in rat vascular tissue NO2- and nitrosothiols, but not nitrate, are converted back to NO' under UVA exposure: NO2- + hv → NO' + O'-."

"The action spectra for NO' release from nitrite and from nitrosothiols have a peak at around 335 nm and lie in the range from 310 to 400 nm.132"

"The skin of a human weighs approximately 4 kg and can be considered the largest human storage organ for NO derivatives such nitrite and nitrosothiols.133 Thus, they represent an important alternative nonenzymatic physiological source of biologically active NO'. Healthy human skin contains 25-fold higher concentrations of NO2- than plasma of healthy volunteers.130 It has been demonstrated in human keratinocytes in vitro and in healthy volunteers that UVA exposure induces NO' in concentrations comparable to, or even higher than, those produced enzymatically by NO synthases.129"

"Low concentrations of NO' protect cultured keratinocytes and skin from oxidative stress and UVA-induced apoptosis.130,131,134"

"It is possible that UVA-induced NO' may protect skin against solar radiation induced damages within 20–30 min, depending on UVA dose. Two independent studies have demonstrated that UVA exposure of human skin specimens leads to non-enzymatic NO' formation which reaches a maximum after 20 min (320–400 nm, 40 J/cm2) or after 30 min (350–400 nm, 30 J/cm2).128,133"

"It has been proposed that UVA-induced NO' may also have antimicrobial effects, be involved in cutaneous wound healing as well as have antitumor activity.130,141"

"UVA-exposure of human skin releases NO' into the circulation. In the bloodstream, NO' can reach the nervous system.129 In this way, UVA can influence transmission of nerve signals indirectly.38"

"However, NO' can represent, not only beneficial effects, but also toxicity, and, due to this, it is known as a Janus molecule.130 Many of the local and systemic UV-induced responses, including erythema and edema formation, inflammation, premature aging and immune suppression, can be influenced by UVA-produced NO'. Its role in the induction and in the progression of skin cancer remains uncertain. The direct toxicity of NO' is modest, but is greatly enhanced by reactions with superoxide (O2'-) to form the powerful oxidant peroxynitrite (ONOO-), which can promote oxidative damage to blood vessels and skin. Under normal conditions O2'- is rapidly removed by superoxide dismutases (SOD). NO' is quickly removed by its rapid diffusion through tissues into red blood cells where it is converted to nitrate and nitrite by a reaction with oxyhemoglobin. This limits the biological half-life of NO' in vivo to less than a second."​

- Using Sunlight to Sustain Life – Functional Performance Systems (FPS)

"Although exposure to sun does contribute to aging of the skin, people who spend years working outdoors have a reduced incidence of cancer of internal organs."

"While ultraviolet light, and even blue light, tend to suppress our cells’ ability to produce energy, those types of light penetrate only a short distance into living tissue, and so it is mainly the skin which is damaged by too much sunlight. Since blood does circulate in the layers of skin which receive ultraviolet rays, prolonged sun exposure can damage the immune system by injuring white blood cells, but usually the stimulating effect of the other types of light that penetrate more deeply offset this effect on the immune system."

"Doesn’t exposure to the sun age you?

This effect is variable, and depends on our hormones and diet.

The unsaturated oils have been identified as a major factor in skin aging. For example, two groups of rabbits were fed diets containing either corn oil or coconut oil, and their backs were shaved, so sunlight could fall directly onto their skin. The animals that ate corn oil developed prematurely wrinkled skin, while the animals that ate coconut oil didn’t show any harm from the sun exposure. In a study at the University of California, photographs of two groups of people were selected, pairing people of the same age, one who had eaten an unsaturated fat rich diet, the other who had eaten a diet low in unsaturated fats. A panel of judges was asked to sort them by their apparent ages, and the subjects who consumed larger amounts of the unsaturated oils were consistently judged to be older than those who ate less, showing the same age-accelerating effects of the unsaturated oils that were demonstrated by the rabbit experiments.

While it is important to avoid overexposure to ultraviolet light, the skin damage that we identify with aging is largely a product of our diet."

"It is common for melanoma to develop on relatively shaded areas, including the middle of the back and the inside of the thigh, unlike the ordinary less malignant skin cancers, which develop most often on the forehead, nose, ear, cheek, and lip, where sun exposure is greatest."

"To avoid the aging and immuno- suppressive side effects of sunlight, it seems best for sunlight to come through a window glass which removes most of the ultraviolet light, and some of the blue light. Plastic film is available which contains copper that removes this harmful part of sunlight, and can be applied to ordinary window glass. Sitting in sunlight coming through a window of this sort, for short times during the day, is very protective. Besides protecting against cancer, it helps to keep the mood and energy level high, by keeping melatonin low and stimulating metabolism."

The film part is Janelle important:
Increased UVA exposures and decreased cutaneous Vitamin D3 levels may be responsible for the increasing incidence of melanoma
The role of glass as a barrier against the transmission of ultraviolet radiation: an experimental study​

"Recently, the polyunsaturated oils have been identified as the main thing in cells that radiation interacts with, to cause cellular damage. Vitamin E, taken internally or even applied to the skin, has been found to reduce the damage produced by exposure to ultraviolet radiation, which is logical, since it interrupts the chain reactions of toxic free-radicals produced when unsaturated oils are oxidized by radiation or other injury. Aspirin has been found to have a similar effect in reducing the harmful effects which develop in the skin after sunlight overexposure. Coconut oil has been used for generations in "suntan lotions," and whether it is absorbed through the skin or eaten as a food, it clearly has a protective antioxidant function. Carotene seems to work with vitamin E in the skin to reduce injury by ultraviolet radiation. Caffeine also has shown a protective action against radiation, but its mechanism of action isn’t clearly understood."

Vitamin C​

"Aspirin reduces the iron content of the blood serum, and also inhibits the formation of the sometimes-toxic prostaglandins from fatty acids."

..and SolBan was born.

"Coconut oil is very resistant to radiation damage and, like vitamin E, tends to stop the chain reactions that occur in unsaturated fats. The old formula for suntan oil, coconut oil with iodine, might turn out to be a safe sunscreen, since the brown iodine absorbs light, as other ” U.V. blockers ” do, but iodine is also an effective chain breaker that inactivates free radicals, and it can’t be absorbed into cells in its brown form. It doesn’t have the potential for causing cancer that the popular sunscreens do."

"Can you get enough sunlight during the summer to hold you through the winter?

No [Wagner, 2018], many of the beneficial effects of bright light disappear during just a few hours of darkness, though the restoration of our tissues that happens during the summer puts us into a better state for surviving the winter, for example by allowing massive regeneration of the thymus to occur. (This occurs in adults, not just in children. The idea that the thymus disappears after puberty is based on autopsies. If a person lives for even 3 hours after an accident or the onset of sickness, the thymus has had time to shrink.)

Frequent short exposures to bright light is almost as valuable as continuous sunlight, and it is less likely to cause skin aging."

"Studies on isolated organs and tissues suggest that a few seconds of penetrating bright light are enough to break the free radical chain reactions, slowing the production of toxic substances, which tend to increase in concentration during nocturnal stress. A few seconds’ exposure to the direct light of ten 150 Watt incandescent bulbs, for just a few minutes every two or three hours, might provide more effective protection than continuous exposure to a single 100 Watt light."​

- Beneficial Effects of UV-Radiation: Vitamin D and beyond

"Several other effects aside from vitamin D synthesis are induced by exposition to UV radiation. The human skin is the largest storage of nitric oxide (NO) and its derivatives. Irradiation with relevant doses of UV-A induces a translocation of NO into the circulation, leading to vasodilatation, reduced vascular resistance, and a reduction in blood pressure [34,120,121,122]. UV radiation may lead to a degradation of folic acid, possibly leading to folate deficiency. As folic acid is involved in DNA synthesis and repair as well as amino acid metabolism, its presence is especially important in pregnant women and it has been proposed to play a significant role in carcinogenesis. Nevertheless, the consequences of this photodegradation on individual health remain unclear and require further research [34,123,124].

Serotonin levels are influenced by sunlight exposure of the skin and the eyes. Serotonin is a neurotransmitter that modulates mood, anxiety, aggression, pain, sexual behavior, and sleep [125]. Additionally, studies reported a risk-lowering effect of serotonin on diabetes mellitus and a risk-increasing effect on arterial hypertension [34,126,127]. Exposure to light also affects melatonin secretion. It is usually secreted at a daily rhythm, with low concentrations during daytime and a peak around midnight. The phase and the amplitude of the peak can be influenced by the amount of exposure to light during daytime. Studies reported anti-oxidant effects of melatonin as well as possible anti-metastatic and anti-angiogenic effects [34,125,128]."​

 

[Amazoniac]

It would take more time to modify the axis, but you get the point:

Nice pixels.

 

[dreamcatcher]

The evidence so far points to low vitamin D levels being both - a result and cause of inflammation, forming a nasty feedback mechanism similar to cortisol/estrogen. I repeatedly said on various threads that in order to know if low vitamin D is truly a deficiency or something else is going on the tests always need to include at a minimum the following biomarkers all tested together: cholecalciferol, 25-OH-D (calcidiol), 1,25-OH-D (calcitriol), 24,25-OH-D, PTH, serum calcium, phosphorus, and prolactin.
If the low vitamin D levels (most doctors typically only test 25-OH-D) are due to inflammatory reaction somewhere, then low 25-OH-D will typically be accompanied by elevated 1,25-OH-D (calcitriol), and possibly 24,25-OH-D as well as prolactina, and PTH will typially be towards bottom end of normal or even low. If the low 25-OH-D are due to plain old deficiency, 1,25-OH-D will be normal or low, prolactin will be normal or low, PTH will be towards the upper limit of normal or even above, LDL will be high, and serum calcium may be elevated. There are many other possible combinations due to various other issues, but this should be a good enough combo of biomarkers to give your doctor a run for his/her money and determine if you truly have vitamin D deficiency or something else is going on.

It's impossible to ask a doctor to do a prolactin test unless he's open minded. My GP laughed at me and said' 'You're not pregnant'.

 

[somuch4food]

So daily sun exposure + 500 IU is enough to turn a calf into a monster.

That seems reductionist. Vitamin D is, but one factor in promoting growth and health.

 

[haidut]

It's impossible to ask a doctor to do a prolactin test unless he's open minded. My GP laughed at me and said' 'You're not pregnant'.

Most GPs need to re-attend medical school. In addition to its role in pregnancy prolactin is well-known as both acute and chronic stress biomarker.
Prolactin - Wikipedia
"...Levels can rise after exercise, high-protein meals, minor surgical procedures,[23] following epileptic seizures[24] or due to physical or emotional stress.[25][26] In a study on female volunteers under hypnosis, prolactin surges resulted from the evocation, with rage, of humiliating experiences, but not from the fantasy of nursing.[26"

Acute psychological stress increases plasma levels of cortisol, prolactin and TSH. - PubMed - NCBI
Chronic sustained stress increases levels of anterior pituitary prolactin mRNA. - PubMed - NCBI

Maybe you can politely show these links to your GP and ask that you want yours tested together with cortisol since you are under stress??

 

[Cirion]

Effects of prolactin does seem to be especially pronounced for those already with health issues. I think this is one of the motivations (besides moral) behind the nofap movement. I know for me, I get hit like a truck with the effects of prolactin so strict nofap is very important for me at least while I'm healing. It would make sense, because from what you just wrote, prolactin is already high in a metabolically compromised individual, so the last thing you need is even more! It's a very under-rated practice IMO, but very few have the discipline to do it, though it's not as necessary if you're already healthy.