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Questions about the pineal gland or so-called “third eye” in humans come up so often in Quora that I’m attempting here to consolidate my previous answers into one general-purpose overview. I’ve put in section heads to help navigate to whatever point may be most relevant to what anyone asks. If your interest is mainly in calcification, “opening” the pineal gland, or the “third-eye” interpretation, you can scroll directly to headers on those and skip the introductory biology.I. What Is the Pineal Gland?The pineal gland is a very small gland, 5 to 8 mm long, in the endocrine system of most vertebrate animals from fish to primates, including humans. It’s named for its resemblance to a pine nut (not a pine cone, as so often misstated). It’s also called the epiphysis cerebri, perhaps a useful search term if you ever go looking for further information on it. In fish, amphibians, and reptiles, the pineal gland is located near the brain surface just under the cranium, but in mammals, growth of the cerebral hemispheres has resulted in it being buried deep in the brain (Figure 1).Figure 1. Human Pineal Gland (at arrow). Compared to Mediterranean Pine Nuts (Pignolias).[1] Brain photo from Quizlet via Google Images (no good URL)..II. What Does the Pineal Gland Do?The pineal gland secretes the hormone melatonin, which is concerned with circadian and seasonal rhythms of physiology and animal behavior. The pineal synthesizes melatonin from the neurotransmitter serotonin. Daily melatonin secretion peaks about 3 to 5 hours after one falls asleep, and its level fluctuates seasonally. In animals with seasonal breeding, it regulates the gonads and onset of breeding behaviors, and it’s involved in seasonal migrations of many species. Some physiologists think the human pineal gland plays a role in the onset of puberty, but the evidence for this is inconclusive. Pineal tumors are sometimes associated with precocial (premature) puberty in young boys,[2] but it’s unclear whether they are the direct cause or whether that results from damage to adjacent brain tissues.In humans, melatonin receptors are widespread throughout the body, including the insulin-producing islet cells of the pancreas. A defect in melatonin receptors reduces the body’s sensitivity to insulin and is associated with type 2 diabetes mellitus. Melatonin has also been implicated in mood disorders such as jet lag, seasonal affective disorder (SAD), and premenstrual syndrome (PMS). However, there is also evidence against its role in any of these, so the jury is still out on that question. Nevertheless, many people claim melatonin to be effective for them in relieving jet lag or aiding sleep. (I have used it myself for sleep.).III. What Is the Structure and Composition of the Pineal Gland?Under the microscope (Figure 2), the pineal gland isn’t a very remarkable or exciting-looking organ, even to those of us who do find excitement in the histology of most organs. Almost every organ looks far more interesting than this under the microscope. The pineal consists mostly of tiny melatonin-secreting cells called pinealocytes, intermingled with supportive cells, neurons, and neuron-like cells.Figure 2. Histology of the Human Pineal Gland. Low and high magnifications.[3]A more interesting feature seen in many tissue sections, however, is accretions called corpora arenacea[4] (singular, corpus arenaceum), also called acervuli (Figure 3). Corpora arenacea translates as “sand bodies” and even some biological authorities refer to these granules as “brain sand,” but that’s only a figure of speech. It leads some people to ask me why the brain contains quartz,[5] like beach sand. Quartz, however, is silicon dioxide (SiO2). Corpora arenacea, on the other hand, are composed of calcium phosphate, calcium carbonate, magnesium phosphate, and ammonium phosphate. Acervuli translates as “little heaps” and is a term also used in botany.Their functional significance, if any, is unknown. With age, they accumulate in the pineal gland and some other brain tissues such as the choroid plexuses. They’re often visible on brain CT scans (Figure 4) by one’s twenties or thirties and thus serve as a radiologic landmark for the location of the pineal. This is what is meant by pineal gland calcification; more on that later.Figure 3. A Pineal Corpus Arenaceum[6] (L) compared to silica (quartz) beach sand[7] (R). Other than being hard granules, there is no resemblance physically or chemically. Beach sand made of pulverized coral and mollusc shells, however, is more chemically similar (calcium carbonates and phosphates) to corpora arenacea.Figure 4. Calcified Pineal Gland (arrow). CT scan of a 63-year-old man. The pineal here is about 7 mm dia.[8] This is sometimes helpful as a radiologic landmark for brain surgery on surrounding tissues..IV. Is the Pineal Gland a Photoreceptor?Humans and other mammals don’t have photoreceptor cells in the pineal gland, but many other vertebrates do. In some fish and most amphibians and reptiles, the pineal is associated with a parietal eye (or colloquially, “third eye” or “pineal eye”) (Figure 5), which contains photoreceptor cells and responds directly to light. There is commonly a thin, transparent area of cranium or a translucent reptilian scale over the parietal eye to give these receptors direct access to sunlight, and in some cases, the pineal gland even protrudes through the skull.Figure 5. Parietal “Third” Eye. L: The bullfrog, Rana catesbiana.[9] R: A lizard, the tuatara, Sphenodon punctatus.[10]The pineal photoreceptor cells of these vertebrates are strikingly similar in some ways to the receptor cells of a retina (rods and cones), especially in their elaborate parallel layers of membrane loaded with visual pigment (Figure 6).Figure 6. Receptor Cells in the Parietal Eye of the Lamprey, Petromyzon.[11] The outer segment (OS in figure B) contains closely spaced membrane layers loaded with visual pigment, like the outer segment of human rods and cones. It is the dense, dark cap on the cell in figure C.In humans and other mammals, however, there is no parietal eye and the pineal gland has no such cells. The skull is too thick and the cerebral hemispheres too massive to allow any light to reach the mammalian pineal gland. A Quora question once asked of me cited an article, “Photoreceptors in pineal gland and brain,” and asked, “Why do people claim that the pineal gland doesn’t have photoreceptors, when research clearly shows otherwise?”[12] Another, citing the same article, asked, “Why would we have photo (color) receptors inside of the pineal gland?”[13]What these questioners overlooked, however, is that those researchers, Okano and Fukada (2000),[14] were studying conelike receptor cells in the pineal glands of more primitive vertebrates (amphibians and reptiles), not humans or any other mammals. Okano and Fukada wrote, “Extracranial pineal organs of submammalians are cone-dominated photoreceptors sensitive to different wavelengths of light” (my added emphasis). They clearly imply that mammals such as ourselves have no such pineal cone cells or color-sensitive pigments. A few lines later, they state “the mammalian pineal is considered by most of the authors as a light-insensitive organ.”[15] In my literature search, the only references I could find to direct pineal sensitivity to light in the endothermic vertebrates pertained to birds..V. Does the Pineal Gland Indirectly Receive Any Information on Environmental Light?Yes, apparently it receives information from the eyes by an indirect route. In the retina, there’s a row of neurons called ganglion cells whose axons form the optic nerve. Most of these synapse in the lateral geniculate nucleus of the thalamus with neurons that continue to the visual cortex of the brain at the back of the head, where we become conscious of seeing something.Figure 7. Histology of the human retina.[16]However, some of the ganglion cells contain their own photosensory pigment, melanopsin, different from the rhodopsin of rods and photopsin of cones. The signals from these ganglion cells travel not to the visual cortex but to brainstem centers that control pupil diameter and to pathways to the pineal gland. These fibers end in an area of the hypothalamus called the suprachiasmatic nucleus, which is involved in our circadian biological clock. A second neuron descends from here down the brainstem and spinal cord, exits the spinal cord in the upper thoracic region, then travels up a chain of sympathetic ganglia to one called the superior cervical ganglion. From here, fibers re-enter the cranial cavity and go back to the pineal gland. The pineal gland thus gets information about the daily cycle of light to darkness, L:D ratio, in our environment. Animal brains use this information about seasonal changes in day length for purposes ranging from fattening up for the winter to migrating to warmer climates. The functional significance of this pathway in humans is unknown..VI. Why Is It Called “The Third Eye”?—Pineal Philosophy and MysticismThe pineal gland was known even as far back as ancient Hellenic physicians and anatomists such as Galen (129–c. 200 CE). It’s not clear who named it, but Galen already knew of it and said it was named for its resemblance to the Mediterranean pine nut (see figure 1).[17] Being so small and deeply embedded in the brain, the pineal gland is one of its most inaccessible objects of study and historically lent itself to more philosophical speculation than empirical science. It’s solitary nature and central location led philosopher René Descartes (1596–1650) to consider it the seat of the human soul. He thought that nerves carried sensations to the pineal gland, causing it to vibrate a little bit, and these vibrations were what we perceive as ideas, thoughts, and memories (M. Catani & S. Sandrone, Brain Renaissance, Oxford Univ. Press, 2015).The idea of a third eye comes from the ancient mystic traditions of India and China—from Hinduism, Buddhism, Taoism, and Zen. These traditions regarded it as an invisible spiritual eye, the gateway to higher consciousness, the sixth chakra of Hinduism. They believed it to be located in the forehead between the two visible eyes—which is nowhere near the pineal gland at the rear of the brain. The third eye notion was popularized in the West by the New Age philosophy emerging in the 1970s with renewed interest in Eastern spiritualism.[18] Religious icons depicting the third eye sometimes bear noticeable resemblance to the parietal eye of nonmammalian, nonavian vertebrates (compare Figure 8A to Figure 5).Figure 8. The Third Eye in Iconography. A: Bust of Shiva from late 9th to early 10th century Cambodia; from the collection of the Musée Guimet in Paris.[19] B: Third eye of Shiva.[20] C: Third eye in New Age poster art.[21]The Russian theosophist Madame Blavatsky (1831–1891) proposed that the mystical third eye of antiquity was in fact the pineal gland known to science.[22] In recent times, spawning a lot of questions in Quora and elsewhere, many self-styled mystics, gurus, spiritual leaders, and writers have commercialized and promoted the notions of “awakening” or “opening” the third eye. Apparently this is profitable, as people will fall for anything (just ask P.T. Barnum). Many seem to be conflating this imaginary eye with the anatomical pineal eye demonstrated in diverse nonmammalian animals, or offering scientific knowledge of the parietal eye as supposed “proof” of what the mystics have said for centuries. They falsely assume that since the pineal gland of other animals is light-sensitive, the human pineal gland is too.Figure 9. Some Popular Books on the Pineal “Third Eye.”.VII. How Can I Open or Activate My Pineal Gland?This is a very common Quora question.[23][24] The answer is, you can’t open it. There’s nothing to open (see figure 2). The idea of opening the pineal gland, supposedly to achieve more spiritual awareness, stems from the unsupported idea of the pineal being an eye. One might obtain spiritual awareness or enlightenment through various meditation techniques from Kundalini Yoga to Transcendental Meditation, and I mean no criticism here of that goal or those methods, but it has nothing to do with the pineal gland. The idea of opening the pineal gland might be construed only metaphorically, but if meant literally—a physical opening that one might observe in pineal autopsies of people who died “enlightened”—I would have to dismiss that as pseudoscientific mumbo-jumbo. If such a hypothesis can’t be tested and supported by empirical evidence, then it’s of no value as objective knowledge.The notion of “activating” the pineal gland apparently originate with Rick Strassman’s book, DMT: The Spirit Molecule (2000)[25] claiming that the pineal gland secretes N, N-dimethyltryptamine (DMT). DMT has been used as a recreational drug since the 1960s for psychotropic effects that some users describe as out-of-body or psychedelic experiences[26] or “getting in touch with external realities.”[27] Strassman relates DMT to alien abduction experiences and speculates that it “facilitates the soul's movement in and out of the body.” I find such fancies of little value, no more worth pursuing than Uri Geller or Eric Von Däniken.DMT occurs in trace amounts in the pineal glands of rats, but it’s not clear that the pineal gland is the source of it; it occurs in other brain regions as well (such as the visual cortex) and it’s present in the same amounts with or without the pineal gland (as found in pinealectomized rats). The mRNA that codes for a DMT-synthesizing enzyme, INMT, occurs in the human pineal gland but also in many other tissues throughout the body, and has other functions beside producing DMT.[28] DMT itself has not been detected in the human pineal gland or brain. The pineal gland produces about 30 micrograms of melatonin per day, and would have to quickly produce 25 milligrams of DMT (a thousand times as much in a small fraction of the time, since it breaks down quickly) to reach the threshold for any psychedelic experience.[29][30] This is implausible, to say the least..VIII. Can I Regulate My Pineal Gland?The only way I’ve heard of to artificially regulate the pineal (modify its function) is phototherapy. Bright light suppresses melatonin secretion and has been found to improve sleep and relieve depression in people who don’t get enough natural sunlight. Night-shift workers, for example, often don’t get enough natural light because they’re awake and working during the night, and sleeping by day while the sun is shining. Sleep disturbance and mood disorders can sometimes be relieved by a brief period (as little as 30 minutes) of bright light per day.I couldn’t readily find good information about options, but I see some companies selling “light boxes” for this (lying down with your head in a box with bright lights); I don’t know if this is effective or just a quack capitalization on popular belief. I’ve heard of some companies (factories, hospitals, etc.) that have night-shift workers offering phototherapy rooms—a small room with bright fluorescent lights all along the walls—where employees can go for a half-hour or so of phototherapy before they go home, said to improve sleep and mood through its action on the pineal. However, failure to find significant results in placebo-controlled trials, combined with concerns about overriding harmful effects, has led to the closing of light-therapy clinics in Sweden.[31].IX. How Can I Decalcify My Pineal Gland?The pineal gland becomes progressively calcified with age, accumulating corpora arenacea even in childhood. These form even in birds but not in any of the other vertebrate groups from fish to reptiles.[32]Other questions have arisen on my feed about whether this is has any effect on pineal or brain function, whether it is harmful, whether fluoride in drinking water affects it, and whether it can be reversed or there is any reason to reverse it.Fluoride does seem to contribute to pineal calcification, as discussed in a study of merganser ducks by Kalisinska et al. (2014)[33] with implications for the mammalian and human pineal. These authors speak in paragraph 4 of neurotoxic effects of fluoride in the brains of mammals like ourselves. In the sparse literature available to date, the reported effects on mammalian brains seem to center on oxidative stress and apoptosis (death by “programmed suicide”) of neurons. Half a dozen of Kalisinska’s references point to putative connections with deficits in learning and memory.As to whether pineal calcification can be reversed or there’s any need or reason to do so, I find little information except for unsubstantiated fad diets and dietary supplement ideas, such as doing it with daily doses of apple cider vinegar—sheer nonsense. The idea is supposedly that malic acid in the vinegar will dissolve the calcium granules in the pineal gland. Vinegar certainly will dissolve calcium salts—anything from antacid tablets to blackboard chalk to animal bones—but a little vinegar taken orally won’t affect body pH and will never get anywhere near the pineal gland. If, hypothetically, it did have the ability to dissolve “brain sand,” it would also have the undesirable effect of softening one’s bones (osteomalacia), and would be bad advice.Many other web sites on the subject have agendas like selling special water filters, blue-blocking eyeglasses, detox regimens, and snake-oil remedies like “Activator X” (yes, a real trade name of one of these). This search leads down a murky rabbit hole of pseudoscience and quackery on which I don’t care to waste any more time and nobody should waste their money.I did find one credible, peer-reviewed article on pineal calcification with a section on hypothetical and empirical pineal rejuvenation. On the empirical side, though, this involved studies in which young pineal glands were transplanted into the eyes (!) of older rats and showed some rejuvenating effect, or in which cells were injected into the pineal glands of chicks (which, unlike the human pineal, are close to the brain surface and easy to access). On the hypothetical side, there is some speculation on whether there are any plausible ways to rejuvenate aging human pineal glands by cell injection or perfusion techniques,[34] but obviously this is no do-it-yourself job..CodaI hope this answers most questions people have about the pineal gland. If new questions, facts, or corrections arise, I’ll edit and update this to whatever extent I feel they may warrant.Footnotes[1] Mediterranean Pine Nuts (Pignolias) | Pine Nuts | Nuts.com[2] Precocious Puberty Due to Human Chorionic Gonadotropin-Secreting Pineal Tumor - PubMed[3] Pineal gland - Wikipedia[4] Corpora arenacea - Wikipedia[5] Why does the pineal gland have quartz in it?[6] Description[7] Microbus Microscope Educational Website[8] Diagnostic accuracy of susceptibility-weighted magnetic resonance imaging for the evaluation of pineal gland calcification[9] Parietal eye - Wikipedia[10] Sphenodon punctatus - Monaco Nature Encyclopedia[11] Figure 10. [Lamprey pineal photoreceptors. A, Schematic...].[12] Why do people claim that the pineal gland doesn’t have photoreceptors, when research clearly shows otherwise?[13] Why would we have photo (color) receptors inside of the pineal gland?[14] [17] Photoreceptors in pineal gland and brain: Cloning, localization, and overexpression[15] (PDF) Nonvisual photoreceptors of the deep brain, pineal organs and retina[16] Anatomy & Physiology: The Unity of Form and Function[17] Descartes and the Pineal Gland[18] New Age - Wikipedia[19] Third eye - Wikipedia[20] Third Eye GIF - Find & Share on GIPHY[21] What is the Third Eye and How can it be opened? What are the benefits?[22] The Secret Doctrine[23] People often talk about the pineal gland. How can a person open the pineal gland? What are the benefits?[24] Is it really possible to open/activate your pineal gland? Or is it a gimmick?[25] DMT: The Spirit Molecule[26] What Is DMT? Everything You Need to Know[27] N,N-Dimethyltryptamine - Wikipedia[28] Biosynthesis and Extracellular Concentrations of N,N-dimethyltryptamine (DMT) in Mammalian Brain[29] No reason to believe the pineal gland alters consciousness by secreting DMT, psychedelic researcher says[30] N,N-dimethyltryptamine and the pineal gland: Separating fact from myth - David E Nichols, 2018[31] Light therapy - Wikipedia[32] Comparative Histology of Pineal Calcification - PubMed[33] Fluoride concentrations in the pineal gland, brain and bone of goosander (Mergus merganser) and its prey in Odra River estuary in Poland[34] Pineal Calcification, Melatonin Production, Aging, Associated Health Consequences and Rejuvenation of the Pineal Gland

How can we be so sure that the ancient scrolls and texts are 100% accurate and depict what actually happened?Ancient texts are not 100% accurate. For that matter, most modern texts are not 100% accurate, but that doesn’t mean they are inaccurate either. That sounds a little paradoxical, doesn’t it? What I mean is that inaccuracies in details don’t prove inaccuracy of the entire document. Think of all the textbooks you have been forced to study as ‘fact’ that still also had mistakes in them.100% accuracy doesn’t exist in ancient documents, which means the real question here is ‘how can I trust anything in writing knowing that?’As Grundy, the author of the atheist blog Deity Shmeity says,“My confidence of the accuracy of historical events goes down exponentially with the paper trail. The idea that history is written by the victors highlights the biases of the past. Books are burned. Records fade. Who should I trust for an accurate portrayal of events two thousand years ago?" [1]He’s right that there is a paper trail. We do not possess the autograph (the original) of even one ancient document. None. All our ancient documents are copies of copies. Ancient texts have not arrived in our modern day as they left the author’s hands.Some interpretations of particular aspects of history do shift as more research is done and more information becomes available. Does this mean history can’t be trusted? That none of those ancient texts can be trusted?It doesn’t—really. Qualified professional historians do quality work assessing those ancient documents and their dependability, working toward the best possible explanation, establishing some facts so clearly they become accepted as a kind of ‘bedrock’ of history.History is similar to science in that some principles are so thoroughly established they are foundational and others fluctuate from new data because we just don’t know everything yet. That doesn’t make science—or history—undependable.All the ancient documents that our understanding of history depends upon are carefully evaluated. So how does that work?A document’s background, authorship, date of writing, place of composition, audience, reason for writing and genre are all looked at.What the document is written on, what kind of ink it is written with, the style of handwriting, and its grammar and vocabulary are examined.Nothing is taken in isolation. Archaeological artifacts are quite valuable aids to assessing the accuracy of an ancient document. Traditions, local histories, oral and written, sometimes reach back into antiquity with sources such as reports, legends, heroic stories, and ballads associated with them—all the literary and non-literary remains of the past are brought to bear.The dates of these copies is considered: the bigger the gap in time between the original and the copy, the more questionable becomes reliable accuracy. Proximity is a plus—less time for errors to creep in.Plato wrote the Tetralogies in the fourth century BC; the earliest copy we have dates to 895AD—a gap of about 1300 years. This is not unusual in dealing with ancient texts and doesn’t prove anything by itself. Seutonius wrote the Twelve Caesars sometime between AD70 and AD140, and the earliest copy we have of it is dated 950AD—900 years after the original—yet Seutonius is considered dependable and accurate because he is supported by other records. (Interestingly enough, Seutonius was more of a biographer than a historian and included everything—rumor and fact—without assessment, much like Luke did in the New Testament.)The Dead Sea scrolls contain a copy of the complete book of Isaiah who lived and wrote in the mid-700s BC. The Qumran copy is dated to the first century BC, a gap of about 600 years. It’s been compared to both the Septuagint and the Masoretic text and has things in common with both.We currently have, in existence today, several papyrus fragments of portions of the New Testament that were copied within a century after the composition of the original documents. While distance in time doesn’t prove inaccuracy, proximity in time argues for accuracy.Comparisons to other documents must be made. That means the amount of manuscript evidence influences this aspect of assessment— the more manuscripts there are, the better. The NT surpasses all other ancient documents in sheer numbers. There are well over five thousand Greek manuscripts of the New Testament, and four times that number in other languages. As Bart Ehrman said: “the textual critic of the New Testament is embarrassed by a wealth of material.”[2]In contrast, we have about 1700 copies of Homer’s Iliad; 193 copies of Sophocles; about sixty non-papyrus manuscripts of Herodotus’ History; 210 manuscripts of Plato’s Tetralogies; and so on.Scholars use linguistics, literary criticism, sociology, archaeology, geography, anthropology—secondary sources like textbooks, other historical writings, monographs, edited volumes—anything that has the potential of shedding light on the document being investigated.Internal factors are also helpful in assessing a document’s reliability. This includes the text itself and also the competence and character of the author. This also helps identify the presence of any additions or omissions or other errors.Since all ancient manuscripts were copied by hand, and it was such a taxing job, some form of human error corrupts them all—(remember most of those Greek and Roman texts are copies made in the Middle Ages). Whether it is skipping over words (or perhaps entire lines), misspellings, false interpretations, or hypercorrections, even the best of scribes could easily succumb to errors. Most were small errors and clearly by accident, corrupting their manuscript without knowing, contributing to the confusion of present scholars trying to figure out what the original manuscript said.The important fact remains that accurate communication is still possible despite technical mistakes in copying.Suppose you got a postcard with two lines on it that said:### HAVE WON10 MILLION DOLLARS.Then you received another one that said,YOU HAVE ###1# MILLION DOLL$#%.Then you got another, and it said,YOU HAVE WON —with no second line at all.Would you be able to figure out the message? I am guessing you would—because having them all to compare to each other makes the mistakes apparent and the message just as obvious.Ancient texts are not 100% accurate. But it doesn’t matter. Errors in ancient texts have been identified, annotated, and generally found to have little to no real impact, by themselves, on the message itself.Historians really are careful, and while we should always remain open to new research, it is still possible for some aspects of history to be accepted as fact—even if it is written down in fallible texts.Footnotes[1] Why History isn't Scientific (And Why It Can Still Tell Us About the Past) [2] http://Bruce M. Metzger and Bart D. Ehrman, The Text of the New Testament: Its Transmission, Corruption, and Restoration, 4th ed. (New York: Oxford, 2005), 51.

We get optimal vitamin D from solar UVB conversion of 7-dehydroxycholesterol in our skin.Foods, OTOH, typically contain only modest amounts of vitamin D, with only a few being truly rich sources of dietary vitamin D.So it's not that dietary vitamin D is poorly absorbed.Rather dietary vitamin D is sub-optimal in engendering sufficiency in vitamin D deficient individuals.To make matters worse, the well-substantiated link between sun exposure and skin cancer drive sun avoidance and widespread sunscreen usage. In combination with increasing indoor lifestyles, these have resulted in global vitamin D deficiency.Thus, overcoming vitamin D deficiency rather than maintaining sufficiency has become the problem du jour.Key difference? For vitamin D sufficient individuals, dietary vitamin D would perhaps suffice for maintenance.But for vitamin D deficient individuals, i.e. increasingly more and more people, vitamin D supplement intake rather than reliance on dietary intake alone becomes necessary.A few statistics help contextualize the gap between recommended and current average vitamin D levels.The US Institute of Medicine defines vitamin D deficiency as serum 25-hydroxyvitamin D3 [25(OH)D3] concentrations <20ng/ml (1).This requirement is based on the classic function of vitamin D to maintain bone homeostasis. However, recently, especially in the 21st century, many new functions of vitamin D have been discovered, ranging from immune system function to reduction in risk for cancer, hypertension, obesity and Type I diabetes (2).Official guidelines based on the decades-old vitamin D = bone health paradigm may thus be outdated (3).The current controversial definition for vitamin D sufficiency is >30ng/ml (1), assessed as circulating 25(OH)D3 levels. Controversial because no consensus yet across age groups and ethnicity nor does it encompass the changing concepts about vitamin D's link to overall health.The US National Health and Nutrition Examination Survey results for 1994 to 2004 (4, 5) showed that US vitamin D sufficiency levels (30 to 60ng/ml) fell from ~60% to ~30% in whites, from ~10% to ~5% in African Americans, and from ~24% to ~6% in Latinos.More than one study suggests that ~70% of adults and ~67% of children aged 1 to 11 years of age in the US have inadequate vitamin D levels (5, 6, 7).Thus, as an example of global trends, vitamin D insufficiency is common in the US population.What are problems associated with dietary vitamin D?Problem with Natural Foods as vitamin D sourcesDiet typically provides modest amounts of vitamin D. Why? Because few foods are natural vitamin D sources (8).Seafood is the relatively richest vitamin D source (9).Oily fish (salmon, mackerel, herring) and sun-dried mushrooms are rich vitamin D sources (8).Feeding on vitamin-D-rich plankton, ocean-raised fish are richer in vitamin D compared to farm-raised varieties (8).For example, farmed salmon fed pelleted food contain only ~10-25% of the vitamin D3 found in wild salmon (10).OTOH, farmed salmon in Norway are fed fish oil and thus contain similar vitamin D3 as wild salmon (11).Problems associated with Fortifying Foods with vitamin DMilk and orange juice sold in the US are fortified with 100IU of vitamin D per 8oz (8, 15).These levels (1IU = 25ng) are considered insufficient in providing circulating vitamin D levels of 30ng/ml.Milk is also a poor fortification choice for the ~50 million Americans, including ~75% of African Americans, who are lactose intolerant (12).Cod liver oil is rich in vitamin D but many commercial cod liver oil preparations also contain large amounts of vitamin A, which creates a two-fold problem.One, it can antagonize the action of vitamin D, at least in a rat model (13).Two, excess vitamin A can cause toxicity (14).An unfortunate legacy of past vitamin D fortificationAccording to Hector DeLuca, an eminent vitamin D researcher, a post-WW II outbreak of 'idiopathic hypercalcemia and related arterial supravascular stenosis' (3) was attributed to vitamin D fortification of food. As a result, such food fortification was stopped in many parts of the world, especially in Europe (16). Thus, while Finland and Sweden allow milk to be fortified with vitamin D3, most other European countries still forbid fortification of dairy products with vitamin D (11).One problem with synthetic vitamin D. Plant (vitamin D2) and Human (vitamin D3) vitamin D are differentCertain plant products such as sun-dried and shitaake mushrooms have abundant vitamin D but it's vitamin D2.vitamin D2 and D3 differencesDifferent side chains and metabolism.Different binding to vitamin D binding protein (DBP), which transports both vitamins through the circulation (2).Daily doses of 1000IU each of vitamin D2 and D3 are equally effective in maintaining serum [25(OH)D3] (17)However, vitamin D3 stayed longer in circulation after intermittent vitamin D supplementation (18, 19, 20).Bottomline? Vitamin D2 or D3 supplementation may not be equivalent for treating vitamin D insufficiency.Does vitamin supplementation help attain vitamin D sufficiency?Studies suggest 1000 IU of vitamin D3/day or 50000 IU twice a month help maintain sufficient circulating [25(OH)D3] levels in individuals who present with vitamin D deficiency and are then treated for 8 weeks with 50000 IU of vitamin D2 per week (21).Vitamin D from food/supplements/skin exposure to UVB is biologically inactive.Needs to be modified to form [25(OH)D3], the storage form of vitamin D, usually in the liver.Small fraction of [25(OH)D3] is then converted to the physiologically active form, 1, 25-dihydroxyvitamin D (22).While various forms such as capsule versus tablets don't appear to have been widely compared in the literature, a compelling study (23) showed vitamin D3 capsule supplementation worked in preventing fractures in the elderly (>65 years of age). Compelling why? If vitamin D3 capsule works in such a vulnerable population, it's likely to work in others as well. US has two pharmaceutical formulations for vitamin D, liquid for pediatric and gelatin capsules for older children and adults (1). Capsules may provide better time-release and absorption compared to tablets.Different methods of vitamin D level assessment exist. This brings to the final wrinkle about vitamin D level levels, namely the tests.Tests for vitamin D levelsTests typically assess circulating levels of [25(OH)D3] for two reasonsIt has ~1000-fold higher circulating concentrations.It has a substantially longer circulating half-life compared to 1, 25-dihydroxyvitamin D.Easy to measure.Circulating levels of [25(OH)D3] thus reflect an intergrated measure of GI tract absorption plus skin synthesis.However, many drawbacks exist25(OH)D3 tests are expensive with problematic reimbursement.25(OH)D3 is measured using different methods.There is as yet no standardized approach for comparing results obtained from different methods (24, 25).How is vitamin D synthesized?vitamin D is not a vitamin.Instead it's a prohormone synthesized in the skin epidermis following exposure to solar UVB radiation (26, 27, 28).Skin cells contain 7-dehydrocholesterol, which absorbs UVB rays from sunlight.UVB absorption opens the B-ring of 7-dehydrocholesterol, converting it to pre-vitamin D3.Body temperature slowly converts pre-vitamin D3 to active vitamin D/cholecalciferol over several hours.The stable circulating form of vitamin D is 25-hydroxyvitamin D3 [25(OH)D3].The biologically active steroid hormone is 1, 25-dihydroxyvitamin D (29).A Caucasian adult in a bathing suit exposed to sun long enough for their skin to turn pink raises serum 25(OH)D to a level comparable to 10 to 20000 IU of vitamin D2 (30).5 to 30 minutes sun exposure of arms and legs between 10Am and 3PM is considered adequate (8).Factors that necessitate oral vitamin D supplementationAge, clothing, latitude, season, skin pigmentation, sunscreen use and time of day influence skin vitamin D synthesis (8).Skin exposure to UVB is much lower in Northern latitudes (25). This is because the zenith angle of the sun becomes more oblique at higher latitudes during fall and winter. As a result ozone efficiently absorbs most UVB radiation before it reaches the earth's surface (11).Thus, at latitudes >37oN, from about mid-October until mid-March, the solar angle is such that skin is unable to convert 7-dehydrocholesterol into vitamin D (11).Stored vitamin D synthesized using summer sunlight is often inadequate to cover the winter months (31).Aging reduces skin 7-dehydrocholesterol by ~50% between 20 and 80 years of age (32), a structural limitation on the amount of vitamin D3 that aging skin can synthesize.Sunscreen use and amount of melanin (brown pigment) in the skin impair the skin's ability to synthesize vitamin D (25, 33, 34).Greater skin pigmentation accounts for the higher prevalence of vitamin D-deficiency in darker-skinned people (35, 36, 37).As for sunscreen, SPF (sun protective factor) as low as 8 or 15 reportedly decrease skin vitamin D3 conversion by 95% (38).Sunscreen use brings us directly to the dilemma that sunlight now represents in our daily lives. On the one hand, judicious sun exposure is necessary to maintain vitamin D levels. OTOH, the well-substantiated link between sun exposure and skin cancer necessitates widespread sunscreen use and even sun avoidance, leading to inevitable vitamin D deficiency. Vitamin D supplements and food fortification thus become necessary to fill this obvious gap.BibliographyHolick, Michael F., et al. "Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline." The Journal of Clinical Endocrinology & Metabolism 96.7 (2011): 1911-1930. Page on endocrine.orgBikle, Daniel. "Nonclassic actions of vitamin D." The Journal of Clinical Endocrinology & Metabolism 94.1 (2009): 26-34. Page on endocrine.orgDeLuca, Hector F. "Evolution of our understanding of vitamin D." Nutrition reviews 66.suppl 2 (2008): S73-S87. Page on 164.208.4Kennel, Kurt A., Matthew T. Drake, and Daniel L. Hurley. "Vitamin D deficiency in adults: when to test and how to treat." Mayo Clinic Proceedings. Vol. 85. No. 8. Elsevier, 2010. Page on colsanitas.comGinde, Adit A., Mark C. Liu, and Carlos A. Camargo. "Demographic differences and trends of vitamin D insufficiency in the US population, 1988-2004." Archives of internal medicine 169.6 (2009): 626-632. Page on 3-ddaily.comBailey, Regan Lucas, et al. "Examination of vitamin intakes among US adults by dietary supplement use." Journal of the Academy of Nutrition and Dietetics 112.5 (2012): 657-663. Page on researchgate.netMansbach, Jonathan M., Adit A. Ginde, and Carlos A. Camargo. "Serum 25-hydroxyvitamin D levels among US children aged 1 to 11 years: do children need more vitamin D?." Pediatrics 124.5 (2009): 1404-1410. Page on ymcdn.comLappe, Joan M. "The role of vitamin D in human health: a paradigm shift." Journal of evidence-based Complementary & alternative Medicine 16.1 (2011): 58-72.Byrdwell, W. Craig, et al. "Analyzing vitamin D in foods and supplements: methodologic challenges." The American journal of clinical nutrition 88.2 (2008): 554S-557S. methodologic challengesChen, Tai C., et al. "Factors that influence the cutaneous synthesis and dietary sources of vitamin D." Archives of biochemistry and biophysics 460.2 (2007): 213-217. Page on nih.govHolick, Michael F. "Vitamin D: a D-Lightful health perspective." Nutrition Reviews 66.suppl 2 (2008): S182-S194. Page on 164.208.4Bloom, Gabrielle, and Paul W. Sherman. "Dairying barriers affect the distribution of lactose malabsorption." Evolution and Human Behavior 26.4 (2005): 301-312. Page on theantlife.comRohde, Cynthia M., et al. "Vitamin A antagonizes the action of vitamin D in rats." The Journal of nutrition 129.12 (1999): 2246-2250. Vitamin A Antagonizes the Action of Vitamin D in RatsLinday, Linda A., et al. "Cod liver oil, the ratio of vitamins A and D, frequent respiratory tract infections, and vitamin D deficiency in young children in the United States." Ann Otol Rhinol Laryngol 119.1 (2010): 64-70. Page on easy-immune-health.comVanchinathan, Veena, and Henry W. Lim. "A dermatologist's perspective on vitamin D." Mayo Clinic Proceedings. Vol. 87. No. 4. Elsevier, 2012. Page on mayoclinicproceedings.orgMarx SJ. Vitamin D and other calciferols. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic and Molecular Bases of Inherited Disease, Vol. 2, 7th edn. New York: McGraw-Hill; 1995:3103–3104.Holick, Michael F., et al. "Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D." The Journal of Clinical Endocrinology & Metabolism 93.3 (2008): 677-681. Page on endocrine.orgTrang, Hoang M., et al. "Evidence that vitamin D3 increases serum 25-hydroxyvitamin D more efficiently than does vitamin D2." The American journal of clinical nutrition 68.4 (1998): 854-858. Page on nutrition.orgArmas, Laura AG, Bruce W. Hollis, and Robert P. Heaney. "Vitamin D2 is much less effective than vitamin D3 in humans." The Journal of Clinical Endocrinology & Metabolism 89.11 (2004): 5387-5391. Page on endocrine.orgRomagnoli, Elisabetta, et al. "Short and long-term variations in serum calciotropic hormones after a single very large dose of ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3) in the elderly." The Journal of Clinical Endocrinology & Metabolism 93.8 (2008): 3015-3020. Page on endocrine.orgHolick, Michael F. "Vitamin D deficiency." New England Journal of Medicine 357.3 (2007): 266-281.Kennel, Kurt A., Matthew T. Drake, and Daniel L. Hurley. "Vitamin D deficiency in adults: when to test and how to treat." Mayo Clinic Proceedings. Vol. 85. No. 8. Elsevier, 2010. Page on colsanitas.com).Trivedi, Daksha P., Richard Doll, and Kay Tee Khaw. "Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial." Bmj 326.7387 (2003): 469. Page on bmj.comHollis, Bruce W. "Measuring 25-hydroxyvitamin D in a clinical environment: challenges and needs." The American journal of clinical nutrition 88.2 (2008): 507S-510S. challenges and needsHolick, Michael F. "Vitamin D status: measurement, interpretation, and clinical application." Annals of epidemiology 19.2 (2009): 73-78. Page on d.mp3vhs.deMason, R. S. "Vitamin D: a hormone for all seasons." Climacteric 14.2 (2011): 197-203 & Messa, Piergiorgio, Carlo Alfieri, and Maria Pia Rastaldi. "Recent insights into vitamin D and its receptor." Journal of nephrology 24.3 (2011): S30. Page on sin-italy.orgHolick, Michael F., et al. "Photosynthesis of previtamin D3 in human skin and the physiologic consequences." Science 210.4466 (1980): 203-205.MacLaughlin, Julia A., R. R. Anderson, and Michael F. Holick. "Spectral character of sunlight modulates photosynthesis of previtamin D3 and its photoisomers in human skin." Science 216.4549 (1982): 1001-1003.Holick, Michael F., and Tai C. Chen. "Vitamin D deficiency: a worldwide problem with health consequences." The American journal of clinical nutrition 87.4 (2008): 1080S-1086S. Page on www.beauty-review.nlHolick, Michael F. "Vitamin D: the underappreciated D-lightful hormone that is important for skeletal and cellular health." Current Opinion in Endocrinology, Diabetes and Obesity 9.1 (2002): 87-98.Heaney, Robert P., et al. "Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol." The American journal of clinical nutrition 77.1 (2003): 204-210. Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferolLappe, Joan M., et al. "Vitamin D status in a rural postmenopausal female population." Journal of the American College of Nutrition 25.5 (2006): 395-402.McCann, Joyce C., and Bruce N. Ames. "Is there convincing biological or behavioral evidence linking vitamin D deficiency to brain dysfunction?." The FASEB Journal 22.4 (2008): 982-1001. Page on bioon.com.cnHolick, Michael F. "High prevalence of vitamin D inadequacy and implications for health." Mayo Clinic Proceedings. Vol. 81. No. 3. Elsevier, 2006. Page on grctech.comHarris, Susan S., and Bess Dawson-Hughes. "Seasonal changes in plasma 25-hydroxyvitamin D concentrations of young American black and white women." The American journal of clinical nutrition 67.6 (1998): 1232-1236. Page on nutrition.orgDawson-Hughes, Bess, Susan S. Harris, and Gerard E. Dallal. "Plasma calcidiol, season, and serum parathyroid hormone concentrations in healthy elderly men and women." The American journal of clinical nutrition 65.1 (1997): 67-71. Page on nutrition.orgArmas, Laura AG, et al. "Ultraviolet-B radiation increases serum 25-hydroxyvitamin D levels: the effect of UVB dose and skin color." Journal of the American Academy of Dermatology 57.4 (2007): 588-593.Matsuoka, Lois Y., et al. "Sunscreens Suppress Cutaneous Vitamin D3 Synthesis*." The Journal of Clinical Endocrinology & Metabolism 64.6 (1987): 1165-1168.Thanks for the A2A, Jaquelyn McBain.