mechanism of action of multivitamins and minerals

Participants in these studies used a wide variety of MVMs containing different combinations and amounts of nutrients. When taken as directed, multivitamins and minerals are not expected to cause serious side effects. JAMA 2017;317:183-9. The USPSTF also noted that beta-carotene supplementation may increase the risk of mortality from CVD. The brand name of Lycopene Multivitamin and Multimineral Capsules presented by Creogenic Pharma is CREPENE. Published online ahead of print. [. Am J Clin Nutr 2007;85:257S-264S. Do Multivitamins Work? The Surprising Truth - Healthline Lycopene Multivitamin and Multimineral Capsules | Works, Dosage & Detail We encourage you to talk to your health care providers (doctor, registered dietitian, pharmacist, etc.) Duplication is encouraged. In one study, for example, investigators assessed the diets and use of MVMs in a large multiethnic cohort of 90,771 men and women ages 45 and older from Los Angeles and Hawaii [16]. Multivitamins are supplements that contain many different vitamins and minerals, sometimes alongside other ingredients ().Given that there's no standard for what constitutes a multivitamin . However, MVMs often have small amounts of certain nutrients, such as calcium, magnesium, and potassium, so supplement users should check product labels. Therefore, these terms refer to products that have widely varying compositions [5]. Nutrition Business Journal. J Nutr 2021;151:1976-82. MVM supplementation modestly but significantly reduced users' risk of developing cancer by 8% but did not reduce the risk of any type of cancer (e.g., of the prostate or colon) or overall cancer mortality [39]. Nausea. The products provided an average of 14 nutrients, although the products with 3 nutrients in 5 trials did not contain a mineral. How Do Multivitamins Work? Everything You Need to Know about Vitamins Mechanisms of antiinflammatory effects of naturally derived secondary Prenatal vitamins mechanism of action - VITAMENTOR Next: . Impact of frequency of multi-vitamin/multi-mineral supplement intake on nutritional adequacy and nutrient deficiencies in U.S. adults. NCCIH and the National Institutes of Health (NIH) provide tools to help you understand the basics and terminology of scientific research so you can make well-informed decisions about your health. Does Alpilean Really Work: Alpilean Is A Natural Weight Loss Supplement Drug Class: Vitamins, Combos. Adults in this age group might not be able to absorb enough of the protein-bound, naturally occurring vitamin B12 in food because gastric acidity tends to decline and atrophic gastritis tends to become more common with age [6]. Nutrients 2018;10(8). JAMA 2022;327:2334-47. However, MVM users had excessive intakes of several nutrients; 1015% had excessive intakes of vitamin A, iron, and zinc, and 4861% had excessive intakes of niacin. Pregnancy vitamin with Omega-3 for baby's brain development. : CD004905. Macrocytic Megaloblastic Anemia. These beneficial effects include a significant increase of glucose uptake by skeletal muscle cells of up to 450%. Breast Cancer Res Treat 2013;141:495-505. Mechanism of action. Vitamins & Minerals in Physiological - Fundamentals and Health The supplement also had no effect on cognitive decline with age [40]. In another RCT of 18,314, smokers, former smokers, and asbestos-exposed persons, participants who took a combination of 30 mg/day of beta-carotene plus 25,000 IU/day of vitamin A (as retinol) had a 28% higher lung cancer risk than those taking a placebo after an average 4-year follow-up period [65]. The use of MVMs resulted in lower odds of low birth weight (less than 2,500 g) by 12%, birth at a smaller size than normal for gestational age by 8%, and premature births (before week 37 of pregnancy) by 10% than use of supplements containing iron with or without folic acid alone or placebo. Pregnancy and birth outcomes This page specifically discusses the use of multivitamins, which typically contain about 26 different vitamins and minerals, and often provide 100% of the Recommended Daily Allowance of these micronutrients. Multinutrients for the treatment of psychiatric symptoms in clinical samples: A systematic review and meta-analysis of randomized controlled trials. Espaol (Spanish) | Print. [, Bailey RL, Fakhouri TH, Park Y, Dwyer JT, Thomas PR, Gahche JJ, et al. Inflammation comes from the Latin word inflammare, which means "to set on fire.". Studies on the association between MVM use and cancer-related deaths include one that followed 7,728 women in the Women's Health Initiative who had invasive breast cancer for an average of 7.1 years after their diagnosis [22]. JAMA Pediatr 2018;172:780-2. Theoretical basis for harm. The products provided an average of 14 nutrients, although the products with 3 nutrients in 5 trials did not contain a mineral. Association of multivitamin and mineral supplementation and risk of cardiovascular disease. Use of MVs or MVMs (not further defined) was associated with an 11% lower risk of colon cancer mortality than among nonusers. Otten JJ, Hellwig JP, Meyers LD (editors). [, Baker LD, Manson JE, Rapp SR, Sesso HD, Gaussoin SA, Shumaker SA, et al. Pregnant people Both observational studies and clinical trials have examined this possibility. We will explore situations that a multivitamin may be health-promoting, as well as if there is a benefit or harm in taking extra nutrients . Folic acid supplementation for the prevention of neural tube defects. Another type of neural control mechanism is the withdrawal reflex, in which the hand is jerked away from a painful stimulus such as broken glass. Obimin Plus is a pre- and postnatal supplement to help provide adequate supply of vitamins, minerals and DHA and EPA, during pregnancy and lactation. The American Academy of Pediatrics adds that all non-breastfed infants ingesting less than 1,000 mL/day of vitamin Dfortified formula or milk should receive a supplement containing 400 IU (10 mcg)/day vitamin D [58]. However, individuals who take MVMs and other supplements and who consume fortified foods and beverages might obtain some nutrients in amounts exceeding the UL, increasing the possibility of adverse effects [62]. Furthermore, men who reported using MVs or MVMs for 20 years or more had a lower risk of major CVD events, stroke, ischemic heart disease, and cardiac revascularization than men who did not take MVs or MVMs. Another team defined MVMs as "full-spectrum" products providing all 12 vitamins plus 10 minerals [9]. Phytochemicals present in honey can mitigate the primary mechanisms of oxidative stress and are deliberated as nutraceutical food responsible for mitigating risk factors for cancer and cardiovascular diseases. Shelf Life/Expiry: 1.5 Years or 18 months from the date of manufacturing. Adding omega-3 fatty acids, lutein and zeaxanthin, or both to the AREDS formulation did not further reduce the risk of progression to advanced AMD. Nutrients 2017; 9: 655. MMWR 2020;69:1557-62. Theres no convincing evidence that MVMs help prevent chronicdisease. Because breastmilk provides little vitamin D, the American Academy of Pediatrics recommends that exclusively and partially breastfed infants receive supplements of 400 IU (10 mcg)/day of vitamin D beginning in the first few days after birth and continued until the infant is weaned and drinks at least 1 liter or 1 quart of vitamin D-fortified formula or whole milk daily [58]. Ophthalmology 2014;121:525-34. One RCT randomized 1,708 participants aged 50 years and older who had had an MI at least 6 weeks earlier to take a daily MVM containing 27 nutrients (many in doses higher than recommended amounts) for a median of 31 months (range 13 to 60 months) or a placebo as well as their standard medications. Multivitamin and multimineral dietary supplements: definitions - PubMed MVMs and MVs accounted for 14% of all purchases of supplements and 38% of all sales of vitamin and mineral supplements in the United States in 2019 [4]. Mechanism of Action Exerts oncotic pressure, which expands volume of circulating blood and maintains cardiac output. Oral high-dose multivitamins and minerals after myocardial infarction. Minerals (especially taken in large doses) can cause side effects such as tooth staining . RCTs Studies of MVMs that have focused on cancer have been observational. In particular, in pregnant women, MVM together with iron and folic acid are recommended to improve birth outcome and reduce low birth weight and rates of miscarriage. Multivitamin - Multimineral Females (36%) were more likely to take one than males (31%). Be sure to check the percent daily value (% DV) to see what proportion of your daily allotment youregetting. U.S. sales of all dietary supplements totaled an estimated $55.7 billion in 2020, including $21.2 billion for all supplements containing vitamins, minerals, or both, of which $8.0 billion was for MVMs and MVs [4]. Foods provide more than vitamins and minerals. There is no one single thing that makes it work. Nutrients 2018, 10, 248. Results from several studies demonstrate both the use of MVMs for nutritional insurance by some individuals and the potential of MVMs to lead to excessive intakes for others. Overall, MVM supplementation was not associated with better cardiovascular outcomes, including lower risk of mortality from CVD and coronary heart disease, or of stroke incidence and mortality. Among children and adolescents, MVM use rates were 11.0% for up to 2 years of age, 34.6% for ages 25 years, 29.5% for ages 611 years, and 17.3% for ages 1219 years [11]. Topically applied minoxidil is generally well tolerated, but common side effects include itching of the eye, itching, irritation at the treated area, and unwanted hair growth elsewhere on the body. The model comprises an oxygenation that is coupled to carbon-carbon bond . [, Kim J, Choi J, Kwon SY, McEvoy JW, Blaha MJ, Blumenthal RS, et al. The studies included a total of 91,074 healthy adults (average age 62 years) taking the MVs or MVMs for an average of 43 months, and the investigators reported 8,794 deaths. However, if you take a blood thinner, such as warfarin (Coumadinand other brand names), talk to your health care provider before taking any MVM or dietary supplement that contains vitamin K (this vitamin lowers themedicines effectiveness, and doctors base the medicines dose partly on the overall amount of vitamin K a person usually consumes in foods. Vitamins and minerals can cause toxicity if consumed in large amounts. The Age-Related Eye Disease Study (AREDS), which was led by NIHs National Eye Institute and concluded in 2001, showed that daily high doses of vitamins C and E, beta-carotene, and the minerals zinc and coppercalled the AREDS formulationcan help slow the progression to advanced age-related macular degeneration (AMD), a blinding eye disease. Most studies of the potential value of MVMs to enhance health and prevent disease have been observational and compared individuals who chose to take MVM supplements with others who did not take supplements. By age 71 or older, 48% of women and 43% of men were taking supplements. What is a Nootropic Stack? The Complete Guide Follow all directions on the product package, or take as directed by your doctor. Taking an MVM increases nutrient intakes and helps people obtain recommended amounts of vitamins and minerals when they do not meet these needs from food alone [9,12]. People who take certain blood thinners, such as warfarin (Coumadin, Jantoven), should talk with their health care providers before taking any MVM or dietary supplement containing vitamin K [67,68]. For example, a manufacturer might label a product containing vitamins C and E, selenium, zinc, and beta-carotene as an antioxidant formula rather than an MVM. [, Keats EC, Haider BA, Tam E, Bhutta ZA. For a reader-friendly overview of Multivitamin/mineral Supplements, see our consumer fact sheet on Multivitamin/mineral Supplements. Am J Clin Nutr 2007;85:325S-7S. Rosenberg IH. MVM and MV supplements have no standard or regulatory definition, such as what nutrients they must contain or in what amounts. These interactions can make a drug less effective, increase the action of a drug, or cause unexpected side effects. Because people with healthier diets and lifestyles are more likely to use dietary supplements, attributing health benefits that are distinct from the benefits of healthy behaviors to the use of supplements is difficult [13]. This document does not contain all possible side effects and others may occur. 10 Best Vitamins for Cats in 2023 - Reviews & Top Picks Chemical name: pantothenic acid. Cancer Causes and Control 2001;12:927-34. The COcoa Supplement and Multivitamin Outcomes Study (COSMOS) was a subsequent clinical trial to investigate whether MVMs might help prevent cancer and CVD in both men and women [42]. Upper Limit. Yet, iron supplements are a leading cause of poisoning in young children, so parents and guardians should keep iron-containing supplements out of the reach ofchildren. The MVM also improved memory and executive function. Cardiovascular disease (CVD) The trial in the United Kingdom that compared an MVM to a placebo found no beneficial or harmful effect of the MVM on preterm births, birth at a smaller size than normal gestational age, or low birth weight. The studies included a total of 2,019,862 participants with a mean age of 57.8 years and had a mean duration of 11.6 years. A meta-analysis of 20 RCTs investigated whether supplementation with MVMs (whose composition varied by study but that contained multiple nutrients including iron and folic acid) by pregnant people led to better birth outcomes than use of supplements containing only iron with or without folic acid or, in one study, a placebo [33]. Vitamins | Cystic Fibrosis Foundation ET, or . NIH State-of-the-Science Panel. Individuals who have poor nutrient intakes from diet alone, consume low-calorie diets, or avoid certain foods (such as strict vegetarians and vegans) might benefit from taking an MVM [60]. Self-reported health without clinically measurable benefits among adult users of multivitamin and multimineral supplements: A cross-sectional study. The report recommends that people following a vegetarian or vegan diet consult their health care provider about whether they need supplementation with iron, vitamin B12, and other nutrients (e.g., choline, iodine, EPA, and DHA). Multivitamins, Vision: Generic, Uses, Side Effects, Dosages - RxList Multivitamins And Minerals (Oral) - EverydayHealth.com The results showed no significant associations between MV or MVM use and risk of major CVD events, including myocardial infarction (MI), stroke, and CVD death. Homocysteine to methionine. USES: This medication is a multivitamin product used to treat or prevent vitamin deficiency due to poor diet, certain illnesses, or during pregnancy. Effects of multivitamin supplement on cataract and age-related macular degeneration in a randomized trial of male physicians. Infants and children It is reasonably priced, and there's enough product to last a single cat about a month. Dietary supplements to enhance exercise and athletic performance come in a variety of forms, including tablets, capsules, liquids, powders, and bars. A total of 41.5% of the women took an MVM (containing 2030 vitamins and minerals in amounts not exceeding the RDAs), an MV (10 or more vitamins in amounts of 100% or more of the RDA), or a "stress multisupplement" (containing at least 10 nutrients, some in amounts more than twice the RDA) at least once a week. Composition of Product: Lycopene + Multivitamins+ Multi minerals. Know the Science features a variety of materials, including interactive modules, quizzes, and videos, as well as links to informative content from Federal resources designed to help consumers make sense of health information. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers among male smokers. New technologies have allowed innovators to discover the mechanisms of action behind the efficacy of specific strains and bacteria-enhancing combinations, through advanced assay analysis, translational models, and even deep dives into public health data. However, MVMs cannot take the place of the variety of foods that are important to a healthy diet, because foods provide other nutrients and components that have benefits for health. Prevalence of dietary supplement use in US children and adolescents, 2003-2014. [, Park S-Y, Murphy SP, Wilkens LR, Henderson BE, Kolonel LN. Vitamin B12 (Cobalamin) Mechanism and Deficiency. Challenges and opportunities in the translation of the science of vitamins. Vitamin D, iron, and zinc are three important ones. Vitamins and Minerals - HelpGuide.org Normally provided in combination with dietary minerals. One team of researchers categorized MVMs more ambiguously as "stress-tab-type," "therapeutic type," and "one-a-day type," so these products probably included MVs as well [8]. A 5000Units (40% as beta carotene), thiamine 1.5mg, riboflavin 1.7mg, niacinamide 20mg, pantothenic acid 10mg, pyridoxine 2mg, Vit. History of changes to this fact sheet, U.S. Department of Health & Human Services, Division of Program Coordination, Planning, and Strategic Initiatives, Strengthening Knowledge and Understanding of Dietary Supplements, Multivitamin/mineral Supplements - Health Professional, My Dietary Supplement and Medicine Record, Analytical Methods and Reference Materials (AMRM), NIH Consortium for Advancing Research on Botanical and Other Natural Products (CARBON) Program, Computer Access to Research on Dietary Supplements (CARDS) Database, Dietary Supplement Ingredient Database (DSID), ODS Funding of Grants & Administrative Supplements: FAQ, Administrative Supplements for Validation Studies of Analytical Methods, Staff Bios, Publications, and Presentations, Federal Working Group on Dietary Supplements, NIH Dietary Supplement Research Coordinating Committee, consumer fact sheet on Multivitamin/mineral Supplements, Dietary Reference Intakes: The Essential Guide to Nutrient Requirements, Multivitamin/Mineral Supplements and Prevention of Chronic Disease, Dietary supplement use among adults: United States, 2017-2018, How to prevent cancer: 10 recommendations, Multivitamins do not promote cardiovascular health, Dietary Guidelines for Americans, 2020-2025, WHO recommendations on antenatal care for a positive pregnancy experience, Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Small Business Research Grant Program (SBIR), About Research Training and Career Development, Training Grant Application, Review, and Award Process, Integrative Medicine Research Lecture Series, Division of Extramural Research Sponsored by NCCIH, Division of Intramural Research Conducted at NCCIH, Dietary Guidelines for Americans 20152020, How To Find Information About Complementary Health Approaches on PubMed, Most individuals can get all of the necessary vitamins and minerals through a healthy eating pattern of nutrient-dense foods. Am J Clin Nutr 2022;115:1501-10. Theragran-M Oral: Uses, Side Effects, Interactions, Pictures - WebMD Target Actions . A number of minerals are essential for health: calcium, phosphorus, potassium, sodium, chloride, magnesium, iron, zinc, iodine, sulfur, cobalt, copper, fluoride, manganese, and selenium. Pharmacodynamics. Nutrients 2017, 9, 849. Multivitamin and iron may also be used for . Am J Clin Nutr 2007;85:308S-13S. This study prospectively followed 18,530 male physicians aged 40 years and older, of whom 20% reported taking an MV or MVM for an average of 12.2 years [24]. In the French Supplmentation en Vitamines et Minraux Antioxydants (SU.VI.MAX) study, investigators randomly assigned 13,017 adults aged 3560 years to receive a placebo or a daily supplement containing moderate amounts of vitamin C (120 mg), vitamin E (30 mg), beta-carotene (6 mg), selenium (100 mcg), and zinc (20 mg) [48]. Others Participants receiving the supplement did not have significantly fewer cardiovascular events, but this finding should be interpreted with caution because many participants did not take the supplement or placebo as directed, and others withdrew from the study early. Supports overall health: Alpilean also contains vitamins and minerals like . In general, MVMs might help people who do not eat a nutritious variety of foods to obtain adequate amounts of essential nutrients. This publication is not copyrighted and is in the public domain. The World Health Organization recommends iron and folic acid supplementation throughout pregnancy [57]. JAMA 2012;308:1751-60. Approximately 7476% of the men and 7275% of the women had adequate intakes on average from food alone of the 17 nutrients examined, but use of MVMs increased the prevalence of adequacy to 84% for the men and 83% for the women. When your child needs vitamin D, iron, and zinc. Multivitamin - Wikipedia Minoxidil - Wikipedia All results were adjusted to exclude potential confounders, such as the use of single vitamin or mineral supplements. The mechanism of action of vitamin K is discussed in terms of a new carbanion model that mimics the proton abstraction from the gamma position of protein-bound glutamate. Over an average follow-up period of 6.3 years, the supplements significantly reduced the risk of progression from intermediate to advanced AMD by 28% and reduced rates of loss of visual acuity by 27%. The randomized Linxian dysplasia nutrition intervention trial after 26 years of follow-up: No effect of multivitamin supplementation on mortality. Ask ODS Recommended Daily Intake of Vitamins and Minerals for Adults. One way to group them is as follows (Table 1): An additional complication for this product category is that many dietary supplements are not labeled as MVMs even though they contain a variety of vitamins and minerals [1]. Estimation of total usual dietary intakes of pregnant women in the United States. These products go by various names, including "multis" and "multiples," and manufacturers determine the combinations and levels of vitamins, minerals, and other ingredients in them. However, MVM use is common in the general population. The mechanism of action of vitamin K - PubMed Men who took a daily MV or MVM had a 2% higher overall risk of cancer, including a 3% higher risk of prostate cancer, 8% higher risk of lung cancer, and a 16% higher risk of leukemia (which increased to 26% higher if they took more than one MV or MVM daily). MVMs providing nutrients at or up to 100% DV do not typically interact with medications. [, Wang J-B, Abnet CC, Fan J-H, Qiao Y-L, Taylor PR. US Preventive Services Task Force recommendation statement. An analysis of dietary supplement use in the United States from the 20172018 National Health and Nutrition Examination Survey (NHANES) found that MVMs (defined as products containing three or more vitamins and at least one mineral) were the most commonly consumed supplement. People in the United States have taken multi-vitamin/mineral (MVM) and multivitamin (MV) dietary supplements since the early 1940s, when the first such products became available [1]. For example, several B vitamins are necessary for basic survival function, such as converting glucose from food into cellular energy (adenosine triphosphate . The DGA adds that infants fed human milk might also require a vitamin B12 supplement if the mother's vitamin B12 status is inadequate, which might occur, for example, if she follows a vegan diet [54]. Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. These stacks can either be a mix within the same type of nootropics, such as a mixture of racetams or between different types, such as mixing choline with ampakines. Women. Saturated fat : A type of fat found in abundance in butter, whole milk, ice cream, full-fat cheese, fatty meats, poultry skin, and palm and coconut . NCCIH has provided this material for your information. Both the men's and women's One a Day 50+ multivitamins, which Miller and Sonpal recommend, contain calcium and vitamin D, a powerful combo for keeping aging bones strong. Nutri-Vet has provided us with their Multi-Vite Paw-Gel for cats that is the best overall supplement available. Multivitamins, vision are available under the following . Vitamins & Minerals | Nutrition | CDC * This fact sheet focuses primarily on these basic, broad-spectrum MVMs. A review of 16 RCTs of MVs and MVMs (containing more than four nutrients including, in most cases, at least one mineral) in 1,719 participants who had at least one of six types of psychiatric symptoms (depression, post-disaster stress, antisocial behavior, behavioral deficits in dementia, attention-deficit/hyperactivity disorder, or autism) found that the supplements provided no clear reduction in symptoms [47]. They belong to the micro nutrients and are required for normal metabolism in layer poultry. Vitamins and minerals are essential substances that our bodies need to develop and function normally. Iron supplements may be recommended for women of childbearing age, pregnant women, preterm infants, older infants, and teenage girls because they are at greater risk of developing deficiency. Manufacturers sometimes offer these MVMs in packs of two or more pills for users to take daily. [, Bailey RL, Pac SG, Fulgoni III VL, Reidy KC, Catalano PM. Arch Intern Med 2004;164:2335-42. A service of the National Library of Medicine, PubMed contains publication information and (in most cases) brief summaries of articles from scientific and medical journals. [, Chan ALF, Leung HWC, Wang S-F. Multivitamin supplement use and risk of breast cancer: A meta-analysis. The USPSTF advises people who are planning to become or capable of becoming pregnant to take a dietary supplement providing 400 to 800 mcg/day of folic acid daily [55]. Inflammation is a biological response of the immune system that can be triggered by many factors, like microbes, infections, and damaged cells. An evidence review commissioned by the U.S. Preventive Services Task Force (USPSTF) included 78 RCTs with 324,837 participants and 6 cohort studies with 390,689 participants [49]. Here are some of the key benefits of consuming red cabbage: Rich in nutrients: Red cabbage is a good source of vitamins and minerals, including vitamin C, vitamin K, vitamin A, potassium, calcium, and iron. However, few randomized clinical trials (RCTs) have been conducted because these studies need to be long enough to show effects on disease risk that go beyond simply identifying intermediate biomarkers that might suggest such risk. This is a fact sheet intended for health professionals. Office of Dietary Supplements. [. Approximately 48% of the men and 52% of the women in this study reported taking an MV or MVM. [, Rautiainen S, Rist PM, Glynn RJ, Buring JE, Gaziano JM,Sesso HD. The study measured rates of major CVD events, including MI, stroke, and CVD death [27]. Wagner CL, Greer FR, and the Section on Breastfeeding and Committee on Nutrition. The FNB notes that RDAs and AIs for nutrients are levels of intake to ingest, on average, each day from the diet [6]. After 7.5 years of use, the supplements lowered total cancer incidence by 31% and all-cause mortality rates by 37% in men but not women. Some experts have hypothesized that MVM use might reduce cancer risk or improve cancer outcomes, possibly because certain nutrients in MVMs might inhibit carcinogenesis or tumor progression. Smokers and, possibly, former smokers should avoid MVM products providing large amounts of beta-carotene or vitamin A because two studies have linked these nutrients to an increased risk of lung cancer in smokers [63]. One meta-analysis of 21 RCTs investigated whether daily use of MVs and MVMs (products containing three or more nutrients) for at least 1 year affected mortality risk [46]. A 2021 meta-analysis of 9 RCTs (not including the study described above) evaluated the use of MVMs (defined as products that included most vitamins and minerals) by 22,773 individuals and a variety of CVD outcomesincluding total CVD incidence and mortality, MI incidence and mortality, and stroke incidence and mortalityand all-cause mortality [29].