Vitamin D (VD) plays a key role in the body's calcium absorption. When VD is deficient, only 10% of the calcium eaten can be absorbed, and no amount of calcium supplementation may help. For people who work and study at desks in modern cities, how can they know whether the sun has produced enough VD? In order to supplement calcium, VD should be supplemented. In what forms should it be supplemented? What should I pay attention to? This article introduces the source, function, and how to supplement vitamin D needed by the human body, as well as the interpretation of blood test results. I hope it will help all new parents and those who need or are supplementing calcium. Written by Shi Jun What is VD? In the early 20th century, doctors studying nutritional deficiencies discovered 13 vitamins. Since the human body cannot synthesize vitamins, scientists have defined vitamins as organic chemicals that must be obtained from the diet. They play a vital role in the body's metabolism, but only need small amounts to work. Vitamin D (VD) is one of these 13 vitamins and is a fat-soluble vitamin (there are 4 fat-soluble vitamins in total: vitamin A, D, E, and K). Although VD is indeed essential for health and only needs a small amount, it should not be considered a vitamin by definition because the human body can synthesize VD on its own. On the contrary, most natural foods, except for fish and egg yolks, do not contain VD. In addition, the VD obtained from food must be converted and processed by the human body before it can play a role. Unlike other common vitamins, VD is not a chemical substance, but a general term for many chemical substances with similar chemical structures. Common VD mainly includes two types: vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol). Figure 1: Chemical structures of vitamin D2 and vitamin D3 Vitamin D2 mainly comes from fungi (such as mushrooms grown in the sun) and some plant-based foods. Ultraviolet B (UVB) in sunlight promotes the formation of vitamin D2 from ergosterol in mushrooms[1]. The process of artificially synthesizing vitamin D2 is also relatively simple. Vitamin D2 can be produced by exposing plant sterols to ultraviolet light. Since the production cost of vitamin D2 is low, it is often added to food. Vitamin D3 is only found in foods of animal origin, such as fatty fish (a term used to describe fish with a fat content of more than 5.0% when all muscles are combined), fish oil, liver, and egg yolks. Natural vitamin D3 in the human body is synthesized from 7-dehydrocholesterol, which is commonly found in the skin. Sunlight is key to the synthesis reaction: UVB in sunlight is the catalyst for the conversion of 7-dehydrocholesterol into vitamin D3[2]. Without UVB in sunlight, no vitamin D3 is produced in the body. The process of artificially synthesizing vitamin D3 is similar to the process of natural production in human and animal skin: 7-dehydrocholesterol is produced from cholesterol, and then UV radiation converts 7-dehydrocholesterol into the D3 form. Figure 2: UV-catalyzed chemical synthesis of vitamins D2 and D3 Whether taken from food or synthesized by the human body itself, vitamin D2 and D3 must undergo further metabolism by the human body before they can take effect. The liver metabolizes vitamin D2 into 25-hydroxyvitamin D2 and vitamin D3 into 25-hydroxyvitamin D3. These two compounds are collectively called 25-hydroxyvitamin D, also known as calcifediol. 25-hydroxyvitamin D is the main circulating form of vitamin D, and its blood level reflects the amount of vitamin D stored in the body. Therefore, doctors usually estimate whether you have enough vitamin D in your body by measuring the level of 25-hydroxyvitamin D in your blood [3]. Although 25-hydroxyvitamin D is used as a test indicator, it still needs to add a final pair of oxygen and hydrogen molecules in the kidneys to become the final active form: 1,25-dihydroxyvitamin D, also known as calcitriol. Figure 3: Metabolism of VD in the human body | Author's drawing Benefits of VD The main function of VD is to increase the intestinal absorption of calcium, thereby regulating bone growth and maintaining bone health. When the human body has enough VD, the body can absorb 30-40% of the calcium in the diet; if VD is deficient, it can only absorb 10-15%. Children with VD deficiency will develop rickets; adults with VD deficiency will develop osteomalacia and osteoporosis. Osteoporosis and fractures As people age, many people (mostly women, but also men) are at risk for osteoporosis, a disease characterized by brittle bones that can break if you fall. It's almost universally acknowledged that vitamin D plays an important role in maintaining bone health. But it's also the most controversial -- while doctors agree that deficiency increases the risk of osteoporosis and fractures, they disagree on the benefits and optimal dosage of vitamin D supplements. Calcium in the blood is essential for the function of nerves, muscles and heart, and its level cannot drop. At this time, if the total amount of calcium in the body is insufficient, in order to cope with the blood's demand for calcium, the body will secrete parathyroid hormone to mobilize calcium from the bones to supplement the calcium in the blood and maintain the blood calcium level so that the heart and nerves can work normally. But in this way, the bones are sacrificed. As the calcium concentration in them decreases, the bones become fragile and prone to fractures. Without enough VD, the intestines cannot effectively absorb calcium from food. Most studies show that a lack of VD increases the risk of osteoporosis and the likelihood of fractures. So, how much VD supplementation can reduce the risk of fractures? Some studies include only women, while others include both men and women; some include only frail, elderly or hospitalized people, while others include healthy people; some studies only supplement with VD, while others use VD and different doses of calcium at the same time; some studies take 400 IU of VD per day, while others take up to 800 IU per day... The research designs vary, so there is no definite answer to this question. Vitamin D is important, but that doesn’t mean you need extra supplements if your vitamin D levels are normal. A meta-analysis published in August 2018 concluded that increasing vitamin D levels in the general population does not reduce the risk of fractures in healthy people [4]. A meta-analysis of 81 studies found that vitamin D supplements did not prevent fractures or falls or improve bone mineral density [5]. For some people who are confirmed to be deficient in vitamin D, additional supplements may have health benefits. There is growing evidence that vitamin D is important to the human body in many other ways. Many tissues in the body, such as the prostate, intestines, heart, blood vessels, muscles, and endocrine glands, express receptors for vitamin D (proteins that bind to vitamin D). Some ongoing research suggests that when vitamin D binds to these receptors, it may have beneficial effects: muscles need it to contract, nerves need it to transmit information between the brain and various parts of the body, and the immune system needs it to fight invading bacteria and viruses [6]. Take samples from any group of patients with any disease and they will almost certainly have lower levels of VD than healthy individuals. Many people have speculated that low VD levels cause the disease - but there is no evidence to prove this. When you are sick, you go out less and have a poor appetite, which can lower your VD levels. Therefore, we cannot determine whether low VD levels are the cause of the disease or a consequence of the disease. Some correlation studies suggest that vitamin D may protect against colon cancer[7] and may even protect against prostate and breast cancer[8]. However, higher levels of vitamin D in the blood have also been associated with a higher incidence of pancreatic cancer[9]. These studies cannot definitively prove that vitamin D deficiency causes disease, nor do they prove that taking vitamin D supplements can reduce the risk of these diseases. At present, it is too early to determine whether low vitamin D status increases the risk of cancer, and whether high levels of vitamin D protect or increase the risk of certain people. Simply put, the principle of whether VD supplementation is needed is: if there is no deficiency, no need to supplement; if there is a deficiency, you need to supplement it to a normal level. How to get enough vitamin D How to get enough vitamin D? Simple answer: Sunlight, food or supplements. How much sunlight does the human body need to naturally synthesize vitamin D3? VD is also called the "sunshine vitamin" because its synthesis requires ultraviolet light/sunlight as a catalyst. The biggest factor affecting the level of VD in the body is light. If you spend most of your time indoors, wear sunscreen all year round, or live in an area with insufficient sunlight, you are likely to lack sufficient light to promote your own synthesis of the VD you need. Small knowledge points When exposed to sunlight through windows indoors, the skin will not develop VD. This is because, although glass is transparent to visible light, it absorbs almost all UVB rays. UVB rays are the rays that can cause sunburn, so they will not cause sunburn when they pass through glass. However, ultraviolet A (UVA) is closer to the visible spectrum than UVB, and about 75% of UVA can pass through ordinary glass. UVA can cause skin damage and genetic mutations. The latter can cause skin cancer. Therefore, glass cannot protect against skin damage caused by the sun. So how much sunlight is enough? One study found that the people of Tirupati in southern India (13.40°N, 77.2°E) only needed half an hour of midday sunlight twice a week to produce enough vitamin D for the human body[10]. The vitamin D synthesized in the skin by sunlight will not be excessive: if the body needs enough, its own synthesis will be reduced. However, in countries further from the equator, where the sun is not as strong, it may take more time to achieve the same results. However, it is also important to be careful not to spend too much time in the sun without sunscreen. This is especially important for people with lighter skin, as sunburn caused by excessive UV rays is a major risk factor for skin cancer [11]. Knowledge point: Use of sunscreen Staying in the sun and wearing sunscreen is a choice that requires a balance of pros and cons. Sunlight contains two forms of rays: ultraviolet A (UVA) and ultraviolet B (UVB). UVB is the energy needed for the skin to synthesize vitamin D. UVA has a longer wavelength, penetrates deeper into the skin, and is associated with skin aging (such as wrinkles). UVB has a shorter wavelength, penetrates shallower into the skin, and is associated with skin burns (such as sunburn). Although UVA and UVB rays affect the skin in different ways, they both damage the DNA of skin cells and cause genetic mutations, which can lead to skin cancer and premature aging. These rays can also damage the eyes, causing cataracts and eyelid cancer, among other things. Appropriate light exposure is good for the body, but excessive ultraviolet radiation is harmful to the body. To protect yourself, you should try to avoid the sun in the summer, especially between 10 a.m. and 2 p.m. When you go out on a sunny day in the summer, either wear a hat with a large brim, a dark long-sleeved shirt and long pants, or apply sunscreen. Sunscreen should have an SPF of at least 15; people with fair skin should choose SPF 30 or above. However, it should be noted that SPF only protects against UVB, so when choosing a sunscreen, you should choose a "broad-spectrum" sunscreen that also protects against UVA. Most importantly, you should apply sunscreen early and reapply often. The required exposure time is also affected by many other factors, such as season, time of day, latitude/altitude of the area, air pollution, skin pigmentation, use of sunscreen, glass and plastic's ability to penetrate UV rays and their aging, etc. (See: The Hazards of UV Rays: Know Yourself and the Enemy, Only Then Can You Stand in a Place Not "Dark" | Unfolding). For example, people living north of 37°N or south of 37°S cannot get enough UVB from the sun to produce all the VD needed by the human body except for a few short months in summer. In addition, skin pigmentation can reduce the production of VD in the skin by more than 90%, so people with dark skin are prone to VD deficiency. What foods contain vitamin D? Vitamin D can also be taken from the diet. Food sources high in vitamin D include fatty fish (such as salmon), fish oil, egg yolks, butter and liver. However, there are not many food resources with high VD content, and it is not easy to get enough from diet alone. One egg yolk contains only about 20 IU (International Units) of VD. You must eat about 10 grams of salmon, 200 grams of halibut, 850 grams of cod, or nearly two 230 grams of canned tuna to get 400 IU of VD. In addition, some processed foods, such as yogurt and orange juice, have additional VD (D2 or D3). Which VD supplement is better? If the test shows that the VD level in the body is indeed low and cannot be improved by lifestyle changes, you can also take VD supplements to supplement it. The VD health supplements on the market include both vitamin D2 and vitamin D3, and there are huge differences between them. Although vitamin D2 and D3 are collectively referred to as VD, their ability to increase the level of VD in the human body is not exactly the same. When the intake is equal, vitamin D3 is more effective than vitamin D2 in increasing the level of calcifediol in the blood [12,13]. A study of 32 elderly women found that a single dose of vitamin D3 (300,000 IU) was almost twice as effective as vitamin D2 in raising calcifediol levels.[14] Other studies have found that vitamin D2 in powdered form is more sensitive to fluctuations in temperature and humidity[15], so it has been found that the amount of vitamin D2 in different brands may differ significantly from the amount stated on the bottle. However, this study only looked at vitamin D2 in powdered form, and it is not clear whether vitamin D2 dissolved in oil would also be unstable. Therefore, if you need additional VD supplementation, you should consider choosing vitamin D3. Since VD is fat-soluble, VD supplements are best taken with foods containing fat. The more VD, the better? Before 1997, the United States recommended that all adults consume 200 IU of VD per day. As more Americans are found to be deficient in VD, it is now recommended that people aged 51 to 70 increase their daily intake to 400 IU, and those over 70 increase it to 600 IU. This is because as people age (especially postmenopausal women), they become less efficient at synthesizing VD and absorbing calcium. Many authoritative organizations now recommend 800-1000 IU of VD per day. Breastfed babies need to pay special attention to VD supplementation because the amount of VD contained in breast milk is relatively low. Babies need 400 IU of VD every day after birth until they drink formula or milk with added VD. In November 2010, an expert committee of the American Medical Association set new "Dietary Reference Intakes" for VD. This intake is based on an assumption: this person does not synthesize VD through sunlight at all and consumes enough calcium. The American Medical Association recommends that VD be obtained from diet or health supplements as shown in Table 1 (note that the upper limit intake is the highest safe amount considered by experts from the American Medical Association; 1mcg = 1µg = 1 microgram): Table 1: VD reference intake recommended by the American Medical Association | Author's drawing So is the more VD the better? Absolutely not, with any good thing there is a risk of overdose. Too much vitamin D can cause abnormally high blood calcium levels, leading to nausea, constipation, loss of appetite, mental confusion, irregular heartbeat and even kidney stones. Like other fat-soluble vitamins, VD is stored in the body's fat. Daily intake fluctuates, and when some days are overdosed, the excess can be stored; when some days are underdosed, the body can use its own reserves. But this also means that with continued excessive intake of VD, the body's stores may accumulate to toxic levels. In these extreme cases, excess VD can increase calcium levels in the blood, causing hematuria, constipation, and even death. But this extreme situation only occurs in the case of extremely large intakes. Currently, a daily dose of ≤2,000 IU is considered safe. Another situation is that thin people (such as infants and children) have less body fat, so there is less storage space for VD. If a large dose of VD is taken, the excess will enter the blood, leading to excessive calcium absorption and even poisoning. It is not clear how long it will take to be dangerous if the upper limit of VD intake is exceeded. Vitamin D toxicity is almost always caused by excessive use of health supplements. Excessive exposure to sunlight will not cause an overdose of vitamin D, because the body's own synthesis is carefully regulated and will not continue when the amount is sufficient. In China, a lot of VD is supplemented in the form of cod liver oil, the main ingredients of which are vitamin A (VA) + VD. Supplementing VA is helpful for children who are deficient in VA. However, most healthy, well-nourished children do not need additional supplements and can easily consume excessive amounts. For example, in the United States, a random sampling survey of more than 3,000 children across the country found that 97% of children under the age of 2 who took multivitamins consumed excessive amounts of VA. Even among young children who did not take health supplements, 15% consumed too much VA[16]. Figure 4: Common “cod liver oil” Excessive intake of vitamin A can have serious consequences: weakness, headache, nausea, dry skin and other symptoms. Long-term excessive intake of vitamin A can cause joint pain and bone decalcification, leading to osteoporosis[17]. Therefore, if you are not deficient in VA, you should choose a single-ingredient health product to supplement VD rather than this compound form. How do you know if you are deficient in vitamin D by testing the level of vitamin D in your blood? As mentioned above, you can measure the level of vitamin D in your body by testing the 25-hydroxy vitamin D in your blood. The problem is not the test itself, but how to interpret the results. Many experts believe that there is a lack of high-quality research data to systematically confirm which cutoff value indicates vitamin D deficiency. 1) Although the standards vary, most experts agree that a blood 25-hydroxyvitamin D level below 12 ng/mL (nanograms/mL) or 30 nmol/L reflects a significant deficiency of vitamin D. (1 nmol/L = 0.4 ng/mL) Table 2: Experts’ opinions on the harmfulness of VD content | Author’s diagram According to this indicator, some people are deficient in VD, and almost no one has too high a level of VD. Generally speaking, the level of 25-hydroxy VD in the blood of young people is higher than that of the elderly, and the level of men is higher than that of women. 1) Breastfed infants. 2) Older people, because their skin cannot produce VD as effectively as it did when they were younger in response to sunlight, and their kidneys cannot convert VD into its active form as well. 3) People with darker skin, because their skin has a lower ability to produce VD from sunlight. 4) Patients with diseases such as Crohn's disease or celiac disease cannot metabolize fat normally, and vitamin D needs to be absorbed through fat. 5) Obese people, because their body fat will bind to VD and prevent it from entering the blood circulation. Interactions between Vitamin D and other drugs Steroid drugs such as prednisone can interfere with the metabolism of Vitamin D. If you take steroid drugs regularly, you need to discuss Vitamin D with your doctor. The diet drug orlistat (brand names include Xenical and Alli) may interfere with vitamin D absorption. So may the cholesterol-lowering drug cholestyramine (brand names include Questran, LoCholest, and Prevalite). People who take these drugs should discuss vitamin D intake with their doctor. Epilepsy drugs such as phenobarbital and dilantin can affect the metabolism of vitamin D and calcium absorption. The same is true for tuberculosis drugs. On the other hand, cholesterol-lowering statins and thiazide diuretics increase VD levels. In summary, in the past, as long as you had a "healthy" tan, your body would naturally produce all the vitamin D you needed. However, with modern people often working indoors and using sunscreen to prevent skin cancer, this traditional experience is no longer applicable to everyone. Today, the solution to ensure adequate intake of vitamin D is to eat fish and eggs, drink milk and juice fortified with vitamin D, and take appropriate doses of vitamin D supplements. The debate over who needs vitamin D and how much should be supplemented continues, but researchers at the Brigham and Women's Hospital, affiliated with Harvard Medical School in Boston, are conducting a long-awaited randomized trial (called VItal) of 25,000 adults to study the effects of vitamin D and omega-3 fatty acid supplementation on cancer, stroke, and heart disease. Results may be available by the end of this year. References 1. R. Jäpelt, J. Jakobsen, Vitamin Dinplants: review of occurrence, analysis, and biosynthesis. Frontiers in Plant Science 4, (2013). 2. M. Wacker, MF Holick, Sunlight and Vitamin D: A global perspective for health. Dermatoendocrinol 5, 51-108 (2013). 3. MF Holick, Vitamin D Status: Measurement, Interpretation, and Clinical Application. Annals of Epidemiology 19, 73-78 (2009). 4.K.Trajanoska et al.,Assessment of the genetic and clinicaldeterminantsoffracture risk:genomewide association and mendelianrandomisationstudy.BMJ362,k3225(2018). 5. MJ Bolland, A. Grey, A. Avenell, Effects of vitamin supplementation on musculoskeletal health: systemic review, meta-analysis, and trial sequential analysis. The Lancet Diabetes & Endocrinology 6, 847-858 (2018). 6. C. Aranow, Vitamin D and the immune system. J Investig Med 59, 881-886 (2011). 7.MLMcCulloughetal.,CirculatingVitaminDandColorectalCancerRisk:AnInternationalPoolingProjectof17Cohorts.JNCI:JournaloftheNationalCancerInstitute111,158-169(2018). 8. CF Garland et al., Therole of vitamin Dincancer prevention. AmJ Public Health 96, 252-261 (2006). 9. RZ Stolzenberg-Solomon, Vitamin D and pancreatic cancer. Annalsofepidemiology 19, 89-95 (2009). 10.CVHarinarayan,MFHolick,UVPrasad,PSVani,G.Himabindu,VitaminDstatusandsunexposureinIndia.Dermatoendocrinol5,130-141(2013). 11. #039, J. Orazio, S. Jarrett, A. Amaro-Ortiz, T. Scott, UV Radiation and the Skin. International Journal of Molecular Sciences 14, 12222-12248 (2013). 12. L. Tripkovicetal., Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: asystematic review and meta-analysis. The American journal of clinical nutrition 95, 1357-1364 (2012). 13. P. Glendenning, GT Chew, CA Inderjeeth, M. Taranto, WDFraser, Calculated free and bioavailable vitamin D metabolite concentrations in vitamin D-deficient hip fracture patients after supplementation with cholecalciferolander gocalciferol. Bone 56, 271-275 (2013). 14. E. Romagnolietal., 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, 3015-3020 (2008). 15. LA Houghton, R. Vieth, The case against gocalciferol (vitamin D2) asavitamin supplement. The American Journal of Clinical Nutrition 84, 694-697 (2006). 16.R.Briefel,C.Hanson,MKFox,T.Novak,P.Ziegler,FeedingInfantsandToddlersStudy:DoVitaminandMineralSupplementsContribut etoNutrientAdequacyorExcessamongUSInfantsandToddlers? Journal of the American Dietetic Association 106, 52.e51-52.e15 (2006). 17. M. Rutkowski, K. Grzegorczyk, Adverse effects of antioxidative vitamins. International Journal of Occupational Medicine and Environmental Health 25, 105-121 (2012). |
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