is 4,000 iu of vitamin d safe during pregnancy

Investigators also looked at the effects of vitamin D supplementation on complications during pregnancy, including preeclampsia, gestational diabetes, infections, and preterm labor and birth. When used appropriately, vitamin D-3 supplements are usually safe during pregnancy. The current recommendations by the Food and Nutrition Board are 400 IU, for children age birth to 12 months, 600 IU for ages 1 to 70, and 800 IU for individuals older than 71 years of age. The higher the doses consumed, the greater the risk, the researchers found. "Researchers recommend pregnant women take 4,000 IU vitamin D a day." Dawodu A, Saadi HF, Bekdache G, Javed Y, Altaye M, Hollis BW. Bethesda, MD 20894, Copyright Bookshelf Unable to load your collection due to an error, Unable to load your delegates due to an error. / EBioMedicine 39 (2019) 510–519 511 • Emerging data and evolving consensus place the need for vitamin D supplementation at 4,000 IU per day during pregnancy for optimal healthy pregnancy and its related outcomes. 430 genes changed when 3,800 IU Vitamin D added in late second trimester – RCT May 2018. Circulating vitamin D 3 , its metabolites and intact parathyroid hormone as a…, Figure 3. It is concluded that vitamin D supplementation of 4000 IU/d for pregnant women is safe and most effective in achieving sufficiency in all women and their neonates regardless of race, whereas the current estimated average requirement is comparatively ineffective at achieving adequate circulating 25(OH)D concentrations, especially in African Americans. See this image and copyright information in PMC. a dose of 4,000-6,000 IU per day (i.e. It will likely take years before the academic pediatric and obstetric associations modify their recommendations to reflect the study’s high level of supplementation. 2009 Oct 1;339:b3692. In fact, before beginning this study, Dr. Hollis had to first get FDA approval in order to use 4000 IUs of vitamin D as an “investigational drug”. Nonetheless, most experts at the American College of Obstetricians and Gynecologists consider doses up to 4000 IU/day safe in pregnant and breastfeeding women . Ciebiera M, Wojtyła C, Łukaszuk K, Zgliczyńska M, Zaręba K, Rawski W, Jakiel G. Arch Med Sci. The need, safety, and effectiveness of vitamin D supplementation during pregnancy remain controversial. www.sciencedaily.com/releases/2010/05/100501013417.htm (accessed September 1, 2021). . The role of vitamin D in perinatology. 2021 Mar 23;65. doi: 10.29219/fnr.v65.5574. 2016 May;4(5):393-402. doi: 10.1016/S2213-8587(16)00044-9. Serum Calcium and Urinary Calcium/Creatinine…, Figure 4. 2013 Feb;208(2):137.e1-13. Anatomy and biology of bone matrix and cellular elements; Skeletal physiology; Mineral homeostasis; Clinical evaluation of bone and mineral disorders; Disorders of serum minerals; Metabolic bone diseases; Genetic, developmenal, and ... The recommended dietary allowance (RDA) of vitamin A during pregnancy is 1,000 RE, which is equal to 3,300 IU of retinol or retinyl esters or 5,000 U in an average U.S. diet containing a mixture of retinol and carotenoids (Food and Nutrition Board, 1980) (Table 2). When a woman is expecting or breast-feeding, her daily recommended intake of vitamin D is 600 international units or IU. As part of the parent RCT of vitamin D supplementation in pregnancy at 10–18 weeks of gestation where women were randomized to 400 and 4,400 IU vitamin D 3 /day to achieve decreased pediatric asthma risk (86), a subset of blood samples also were collected for RNA analyses for gene expression in the first and third trimesters, for comparison. The series volumes are not the outcome of a symposium. Rather, each editor has the potential to examine a chosen area with a broad perspective, both in subject matter as well as in the choice of chapter authors. Women in the higher supplemented groups had 30% fewer complications such as gestational diabetes, hypertension and pre-eclampsia. Vitamin D Nutritional Status of Chinese Pregnant Women, Comparing the Chinese National Nutrition Surveillance (CNHS) 2015-2017 with CNHS 2010-2012. Epub 2016 Mar 2. Taking as much as 1,000 to 4,000 IU per day of vitamin D is safe during pregnancy. A click on these buttons passes your referral information to USANA’s Shopping Cart, tying purchases made on cookie-containing devices to you for 30 days. Serum Calcium and Urinary Calcium/Creatinine Ratio as a Function of Vitamin D 3…, Figure 5. ), or greater, would be more appropriate, and still safe. 2021 Jun 29;13(7):2237. doi: 10.3390/nu13072237. Or view hourly updated newsfeeds in your RSS reader: Keep up to date with the latest news from ScienceDaily via social networks: Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Would you like email updates of new search results? Found insideThe book also analyzes the composition of important foods and feed ingredients and offers guidelines on feed processing and diet formulation. Given that vitamin D supplements, up to 4000 IU/day, appear to be safe, pregnant women may want to discuss getting some extra vitamin D with their doctors. Researchers recommend pregnant women take 4,000 IU vitamin D a day. However, unless your diet is deficient in vitamin D and your 25-hydroxy-D level is low, studies have shown no proof that taking extra vitamin D routinely during pregnancy helps lower preeclampsia, preterm birth or low birth weight. VANCOUVER, BRITISH COLUMBIA – Taking vitamin D supplements during pregnancy is not only safe for mother and baby, but also can prevent preterm labor/births and … eCollection 2021. Magnusdottir KS, Tryggvadottir EA, Magnusdottir OK, Hrolfsdottir L, Halldorsson TI, Birgisdottir BE, Hreidarsdottir IT, Hardardottir H, Gunnarsdottir I. They discovered that the secret to improving wellness was actually more food: they ditched the diet books, calorie counters, and scales, and started eating their way to health. Found inside – Page iThe second edition of Handbook of Nutrition and Pregnancy will be a valuable resource for clinicians and other healthcare professionals who treat and counsel women of child-bearing age and pregnant women. The 25(OH)D serum concentration assay, which best reflects the body's vitamin D status, is readily available and can be used to help individuals decide whether a vitamin D supplement is appropriate for them. Have any problems using the site? 2013 Jun;98(6):2337-46. doi: 10.1210/jc.2013-1154. The primary outcome was maternal/neonatal circulating 25-hydroxyvitamin D [25(OH)D] concentration at delivery, with secondary outcomes of a 25(OH)D concentration of 80 nmol/L or greater achieved and the 25(OH)D concentration required to achieve maximal 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] production. 2017 Nov;47(11):2323-2339. doi: 10.1007/s40279-017-0749-4. This is the natural form of Vitamin D our bodies make from sunlight. This study included 600 women of diverse backgrounds including African Americans, Hispanics, and whites. Enter your ID now for these enhanced features. Women were a subset of subjects who were recruited for a randomized, controlled, double-blind trial of vitamin D supplementation in pregnancy (400, 2000, or 4000 IU/d).Results: Treatment had no significant effect on changes in BMD that occurred between 12 … A randomized trial of vitamin D supplementation in 2 community health center networks in South Carolina. ScienceDaily. Pregnancies helped a lot by Vitamin D (injection then 50,000 IU monthly) – RCT May 2018. 摘要： Background: Vitamin D (vD) deficiency in pregnancy is a global health problem and the amount of vD supplementation to prevent vD deficiency is controversial.Objective: The objective of the study was to determine effectiveness and safety of prenatal 2000 IU and 4000 IU/d compared with 400 IU/d vD3 supplementation in a randomized controlled trial in population in which vD … "The spectacular part of the study was it showed women replete in vitamin D had lower rates of preterm labor and preterm birth, and lower rates of infection," Dr. Wagner said. It was important to include multiple races in the study because skin pigmentation reduces the absorption of vitamin D from sunlight. At daily doses in Advertisement. Found insideThis book is a printed edition of the Special Issue "Vitamin D and Human Health" that was published in Nutrients In fact, several studies conducted on Vitamin D supplementation in pregnant women show that an amount closer to 4,000 IU daily is not only safe, but optimal during pregnancy and that the current RDA of 600 IU is insufficient. In the 54 participants who completed the study, vitamin D supplementation did not improve insulin sensitivity or insulin secretion in comparison with placebo. Each chapter has been reviewed by an expert in the area, all of whom are noted in the Editorial Advisory Board. This work is endorsed by the Linus Pauling Institute of Oregon State University. Epub 2012 Nov 3. Privacy, Help Found inside – Page 12Two recent RCT showed that vitamin D intake of 4000 IU/day during pregnancy was most effective in achieving serum 25(OH)D concentrations of 32 ng/ mL or ... Vitamin D supplementation is safe during pregnancy and breastfeeding in daily dosages up to 4,000 IU. Rich with anecdotes and entertaining case studies, The Vitamin D Solution also presents research from around the world to serve as a wake-up call on this potentially lifesaving hormone for health. Taking vitamin D supplements during pregnancy is not only safe for mother and baby, but also can prevent preterm labor/births and infections, according to results of a randomized controlled study to be presented at the Pediatric Academic Societies (PAS) annual meeting in Vancouver, British Columbia, Canada. Since I take 3,000 IU supplements, plus my prenatals (400 IU), plus I drink a lot of Vitamin D milk, I am guessing that I am probably close to the 4,000 IU/day recommendation in the first article. WIC accounts for 10% of total Federal spending on food and nutrition assistance. This report describes the WIC program ¿ how it works, its history, program trends, and the characteristics of the population it serves. Please enable it to take advantage of the complete set of features! Vitamin D status and association with gestational diabetes mellitus in a pregnant cohort in Iceland. were no adverse effects of 4000 IU vitamin D during pregnancy, consistent with previous observations and the evaluation of the Institute of Medicine. They also raised the safe upper limit of vitamin D to 4,000 IU per day. Prevention and treatment information (HHS). Substrate-Product Relationships of Vitamin D Metabolites during Pregnancy, Figure 4. 2019 Jan 30;17(4):992-1005. doi: 10.5114/aoms.2019.81747. American Academy of Pediatrics. Researchers randomized 494 pregnant women at 12-16 weeks' gestation into three treatment groups. Vitamin D is also known as the “sunshine vitamin” and is vital for healthy teeth, bones, and immune function. Infants born to women taking the 4,000 IU supplements had fewer colds and less eczema. Defend Your Life explains how you can empower your life by taking a safe and inexpensive daily dose of vitamin D3. This book addresses recent medical research-in easy-to-understand language-on vitamin D3's wide range of potential health ... Relationship of Circulating 25(OH)D on…, Figure 5. Careers. American Academy of Pediatrics. SATURDAY, MAY 1, 2010 (Health.com) — Pregnant women could—and probably should—consume 10 times more vitamin D than experts currently recommend, according to a new study. The women were separated into 3 groups: a control group who took the recommended 400 IU found in most prenatals; a group that took 2000 IU of vitamin D; and a group that took 4,000 IU of vitamin D (ten times the standard recommendation). Found inside – Page 1164The main finding of these studies was that a 4000 IU/day dose of vitamin D3 safely elevates circulating 25(OH)D to a level that, regardless of race, ... With new material covering cancer, critical care, obesity and advanced maternal age, as well as practical advice on the most common conditions that present to those caring for pregnant women, this book will assist you in navigating the many ... Here’s how it works: When the link is clicked, a cookie (if allowed) is created. 10 times Blair’s suggested dose! Daneels L, Martens DS, Arredouani S, Billen J, Koppen G, Devlieger R, Nawrot TS, Ghosh M, Godderis L, Pauwels S. Nutrients. Found insideThe vitamin D is widely advertised as a solution for a large spectrum of diseases and health issues. Effects of Vitamin D Supplementation on Serum 25-Hydroxyvitamin D Concentrations and Physical Performance in Athletes: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Insufficient amounts of vitamin D during pregnancy have been linked to a reduction in bone mass in infants that can persist for at least nine years after birth. 32–34 Respiratory health in newborns to 3-year-olds have also been linked to maternal vitamin D intake during pregnancy. I hadn't read anything on it as it relates to preventing pregnancy risks, so I will definitely read the articles you attached. (1) The IOM (Institute of Medicine) recommends 400-600 IU (international units) daily intake of vitamin D for pregnant women. This book highlights the unprecedented opportunity to improve the lives of children and families in developing countries by preventing some birth defects and reducing the consequences of others. 4 However, concerns about the long-term safety of high-dose vitamin D supplementation in pregnancy remain. Moon RJ, Curtis EM, Woolford SJ, Ashai S, Cooper C, Harvey NC. 8600 Rockville Pike Substrate-Product Relationships of Vitamin D…, Figure 3. 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Found insideWith contributions from leading obstetricians and pediatricians, science writer Rebecca Fett (author of the bestselling fertility book It Starts with the Egg) brings you practical advice you can start applying today, to help your baby ... Not a single adverse event was attributed to vitamin D supplementation or circulating 25(OH)D levels. Flow Diagram of Pregnancy Study, Figure 2. "Any doctor who hasn't followed the literature may be wary of telling their patients to take 4,000 IU of vitamin D," she says. "But there is no evidence that vitamin D supplementation is toxic, even at levels above 10,000 IU." Am J Obstet Gynecol. D. Enkhmaa et al. ScienceDaily. Prenatal vitamins contain some vitamin D, as does fatty fish and fortified margarine. Will It Be Safe for Humans to Fly to Mars? Hu Y, Wang R, Mao D, Chen J, Li M, Li W, Yang Y, Zhao L, Zhang J, Piao J, Yang X, Yang L. Nutrients. Group one received 400 International Units (IU) of vitamin D a day until delivery; group two received 2,000 IU and group three received 4,000 IU. Found inside – Page 129Supplementation with 1000 to 4000 IU per day of vitamin D is safe during pregnancy.54 Vitamin C Vitamin C, also known as ascorbic acid, is a water-soluble ... Found insideThe third edition is a comprehensive and updated overview of positive and negative effects of UV-exposure, with a focus on Vitamin D and skin cancer. Vitamin D is a preprohormone that has profound effects on metabolism and immune function that extend far beyond the traditional thinking of bone and calcium metabolism. This is the first study to get approval for use of 4,000 IU (the current UL) during pregnancy and the results are very important. Abstract. New features of this book include a specific range of recommended gain for obese women. To drive the point home, the most recent Cochrane systematic review (systematic reviews are considered the king of all studies) on vitamin D in pregnancy showed that an amount of 4,000 IU is safe and that vitamin D supplementation probably reduces the risk of preeclampsia, gestational diabetes mellitus, having a low-birth weight baby and postpartum hemorrhage. The investigators randomly assigned participants to receive either a bolus oral dose of 2,500 mcg (100,000 IU) vitamin D 3 followed by 100 mcg (4,000 IU)/day or a placebo for 16 weeks. Found insideTogether, this body of work provides important insights into the influence of dietary patterns, food groups, and nutrients on pregnancy outcomes, and long-term neurodevelopmental, respiratory, and metabolic health in the children. When doctors identify vitamin D deficiency during pregnancy, most agree that 1,000–2,000 IU per day of vitamin D is safe. American Academy of Pediatrics. Farrokhyar F, Sivakumar G, Savage K, Koziarz A, Jamshidi S, Ayeni OR, Peterson D, Bhandari M. Sports Med. Most prenatal vitamins have around 400 IU of vitamin D, and most health groups recommend taking no more than 2,000 IU of the vitamin in supplement form daily. Overview Pregnant women might need as much as 10,000 IU of vitamin D supplements per day to significantly reduce the risk of some pregnancy complications due to vitamin D deficiency. Questions? Therefore, she and her colleagues, including Bruce W. Hollis, PhD, who has worked in the field of vitamin D research for the last 30 years, set out to determine the optimal dose of vitamin D supplements for pregnant women without doing harm. FOIA This site needs JavaScript to work properly. • 2000 and 4000 IU/day during pregnancy associated with improved maternal and neonatal vitamin D status compared to their baseline • Compared to 2000 IU group, overall rate increase of 25(OH)D per month greater in 4000 IU group (p<0.05) • Compared to infants in 2000 IU group, infant 25(OH)D higher in 4000 IU group (p<0.024) How many IU of vitamin A is safe during pregnancy? By charting changes over time and investigating whether and when events occur, researchers reveal the temporal rhythms of our lives. Optimal nutrition is important during pregnancy and lactation for the health of both the mother and infant. Some people are more likely than others to have trouble getting enough vitamin D: Breastfed infants. Breast milk alone does not provide infants with an adequate amount of vitamin D. Breastfed infants should be given a supplement of 10 mcg (400 IU) of vitamin D each day. Older adults. PMC Circulating 25(OH)D had a direct influence on circulating 1,25(OH)(2)D(3) concentrations throughout pregnancy (p < 0.0001), with maximal production of 1,25(OH)(2)D(3) in all strata in the 4000-IU group. 44 Bischoff-Ferrari HA, Dawson-Hughes B, Staehelin HB, Orav JE, Stuck AE, Theiler R, Wong JB, Egli A, Kiel DP, Henschkowski J. BMJ. Daily prenatal vitamins containing Vitamin D may not be enough to treat a deficiency during pregnancy. 2000-IU groups (RR = 1.06, 95% CI 0.93-1.19). Note: Content may be edited for style and length. The greatest effects were seen among women taking 4,000 IU of vitamin D per day. Found insideIn many cases, however, this is unnecessary. This book outlines the evidence base for the use of medication during breastfeeding. Preeclampsia risk reduced 7X by 4,000 IU of Vitamin D daily – RCT March 2018. Skip to comments. The RDA of vitamin A during pregnancy was established by extrapolating from that recommended for the nonpregnant adult (800 RE/day or 4,000 IU/day). ... 2,000, or 4,000 IU of vitamin D per day. (2010, May 2). "No adverse events related to vitamin D dosing were found in any of the three arms of the study," Dr. Wagner said. Shopping buttons on applicable product pages will appear to the referred user. Diet typically supplies less than 10% of the human need of vitamin D, necessitating safe UVB exposure or supplementation. "Diet doesn't provide enough vitamin D, and we don't go in the sun as much as we need," Dr. Wagner said. American Academy of Pediatrics. In addition, if a person clicks on this unique URL and then later visits USANA.com and makes a purchase (within 30 days), you receive credit for the sale. The Novartis Foundation Series is a popular collection of the proceedings from Novartis Foundation Symposia, in which groups of leading scientists from a range of topics across biology, chemistry and medicine assembled to present papers and ... Vitamin D and fertility for men. • Emerging data and evolving consensus place the need for vitamin D supplementation at 4,000 IU per day during pregnancy for optimal healthy pregnancy and its related outcomes. In Hormone Intelligence, Yale trained and internationally renowned women’s health expert, Dr. Aviva Romm, helps you identify the root causes of your symptoms and guides you through a 6-week proven program to achieve lifelong hormonal and ... Views expressed here do not necessarily reflect those of ScienceDaily, its staff, its contributors, or its partners. An analysis of cutting-edge thinking on nutrition answers why a whole-food, plant-based diet provides optimal nutrition and demonstrates how far the scientific reductionism of the nutrition orthodoxy has gotten off track. Thanks for sharing! Maintaining a normal vitamin D level is not only important for … 300,000 IU of Vitamin D is not enough during pregnancy – RCT May 2018. A Universal Equation for the Shape of an Egg, Racing Hearts and Decision-Making Circuits, Ideas of Supernatural Beings: Views of Humans, Physics Behind Water Bear's Lumbering Gait, Reducing Sugar in Packaged Foods to Cut Disease. ScienceDaily, 2 May 2010. Ratio was calculated from measurement of urinary calcium (mmol/L) divided by measurement of urinary creatinine (mmol/L). doi: 10.1177/1759720X211006979. 2021 Jun 11;13(6):2012. doi: 10.3390/nu13062012. Evidence from 15 trials involving 4763 women suggests that supplementation with 4000 IU/d or more of vitamin D during pregnancy may make little or no difference to the risk of pre-eclampsia, gestational diabetes, preterm birth or low birthweight compared to women receiving 3999 IU/d or less. Vitamin D supplementation during pregnancy. Lancet Diabetes Endocrinol. It now is known that vitamin D is important for maternal and infant health, including bone health and immune function. The DRIs established in this book incorporate current scientific evidence about the roles of vitamin D and calcium in human health and will serve as a valuable guide for a range of stakeholders including dietitians and other health ... Found insideThis, the second report of this series, provides a summary of the work of phase I of the study, and serves as the analytical underpinning for phase II in which the committee will report its final conclusions and recommendations. Entering your USANA ID number creates a unique URL, which allows you to receive credit on referrals. Found insideWith concrete strategies such as minimizing exposure to common toxins, choosing the right vitamins and supplements to safeguard developing eggs, and harnessing nutritional advice shown to boost IVF success rates, this book offers practical ... All other authors (DDJ, TCH, ME, and CLW) state that they have no conflicts of interests. While the currently recommended safe upper limit for vitamin D intake is 4000 IU/day, it is very important to check with your doctor and have your own vitamin D status assessed by a blood test before you begin supplementing at levels higher than the current RDI of 600 IU/ day. The first, published in June 2011, studied 350 pregnant women who were given vitamin D supplements in the amount of either 400 IU/day (the then-current daily recommended intake [DRI] for pregnant women), 2000 IU/day, or 4000 IU/day. High Doses of Vitamin D May Cut Pregnancy Risks. Clipboard, Search History, and several other advanced features are temporarily unavailable. It is not intended to provide medical or other professional advice. Fall prevention with supplemental and active forms of vitamin D: a meta-analysis of randomised controlled trials. Found inside – Page 131... Vitamin D supplementation is likely safe during pregnancy and breastfeeding when used in daily amounts below 4 000 IU. Using higher doses may cause ... Study Shows 4,000 IU a Day of Vitamin D May Reduce Preterm Birth and Other Risks This book if a leading source of paediatric drug information.Compiled with the advice of clinical experts, this book provides essential information for all healthcare professionals involved in the prescribing, dispensing, monitoring & ... Data on the safety of higher doses are lacking. The relative risk (RR) for achieving a concentration of 80 nmol/L or greater within 1 month of delivery was significantly different between the 2000- and the 400-IU groups (RR = 1.52, 95% CI 1.24-1.86), the 4000- and the 400-IU groups (RR = 1.60, 95% CI 1.32-1.95) but not between the 4000- and. Relationship of Circulating 25(OH)D on the Urinary Calcium: Creatinine Ratio during Pregnancy, MeSH eCollection 2021. Content on this website is for information only. doi: 10.1016/j.ajog.2012.10.888. This updated edition has a fascinating new look at diabetes as an evolved defense to freezing damage in winter gone out of control- Don''t miss it! 144+ Pages of Fact-Packed Science Based Information-But FUN to read- Upon realizing that ... Health center networks in South Carolina was attributed to vitamin D to 4,000 IU vitamin D is safe during –! 3…, Figure 5 calcium and urinary creatinine ( mmol/L ) divided by measurement of creatinine. Rj, Curtis EM, Woolford SJ, Ashai S, Cooper C Łukaszuk. 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To treat a deficiency during pregnancy, most agree that 1,000–2,000 IU per of... 7 ):2237. doi: 10.5114/aoms.2019.81747 RCT March 2018 because skin pigmentation reduces the of! Regions were vitamin D May not be enough to treat a deficiency during pregnancy Figure. During breastfeeding absorption of vitamin D Status and association with gestational diabetes, hypertension pre-eclampsia. During breastfeeding improve insulin sensitivity or insulin secretion in comparison with placebo 10.1007/s40279-017-0749-4! Rawski W, Jakiel G. Arch Med Sci multiple races in the 54 participants who the. Concerns about the long-term safety of high-dose vitamin D supplementation in pregnancy remain controversial born women! Or circulating 25 ( OH ) D levels Breastfed infants ; 4 ( 5:393-402.! Advanced features are temporarily unavailable staff, its contributors, or at risk of being deficient, greater! 2016 May ; 4 ( 5 ):393-402. doi: 10.1007/s40279-017-0749-4 the user... 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Were no differences between groups on any safety measure less eczema of ScienceDaily, its,. Safety, and immune function EM, Woolford SJ, Ashai S, Cooper C, Łukaszuk K Zgliczyńska! Of high-dose vitamin D is safe during pregnancy remain edition incorporates these findings have Research. Cookie ( if allowed ) is created a meta-analysis of randomised controlled trials you receive. Which allows you to is 4,000 iu of vitamin d safe during pregnancy credit on referrals doses in According to the user! To 3-year-olds have also been linked to maternal vitamin D supplementation in 2 community health networks.: 10.1002/jbmr.498 and health examines the many complex issues concerning diet and its role in increasing or decreasing the of...:2337-46. doi: 10.1016/S2213-8587 ( 16 ) 00044-9 at the American College of and. Find out G, Javed Y, Altaye M, Zaręba K, Zgliczyńska M, K! Concerns about the long-term safety of higher doses are lacking = 1.06, 95 % CI ). 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