The Fat-Soluble Vitamins: A, D, E and K
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Nutrients for strong bones and a healthy heart
Vitamins are classified into two groups: fat-soluble (vitamins A, D, E, and K) and water-soluble (B-complex vitamins and vitamin C). Fat-soluble vitamins are absorbed best when consumed with higher-fat foods. Fatty fish, vegetable oils, green vegetables, and nuts and seeds are good sources of vitamins A, D, E, and K, collectively., However, it’s becoming clear that our human requirements for vitamins D and K may be higher than previously anticipated, and many individuals may have insufficient intakes of these vitamins.,,,,
The main natural source of vitamin D is from skin exposure to ultraviolet rays from the sun. Spending most of the day indoors – along with sunscreen use – makes it difficult to get enough vitamin D, and may explain why vitamin D deficiency is so common. Other major factors which contribute to vitamin D deficiency include living at higher latitudes and having darker skin color. About 30% of us also may have insufficient levels of vitamin K. And those of us with certain gastrointestinal conditions – such as celiac disease, irritable bowel syndrome, inflammatory bowel disease, or other digestive ailments or gallbladder disease – may have insufficient levels of all of the fat-soluble vitamins. These vitamin deficiencies contribute to the incidence of osteoporosis and cardiovascular disease.
Although fat soluble vitamins were first discovered some 100 years ago, scientists are continuing to unravel new mechanisms by which they act in the body and to assess the levels needed for optimal health. Below are the highlights of some of their findings.
Fat-soluble vitamins and your bones
Insufficient vitamin D or K leads to a gradual decrease in bone mineral density (BMD), which increases the risk of osteoporosis, falling, and bone fractures with age.,, In Norway, where the incidence of hip fracture is among the highest in the world, researchers discovered that blood concentrations of both vitamin K and vitamin D were significantly lower in hip fracture patients compared with controls.
We now know that vitamins D and K work together to keep bones healthy. Vitamin D increases the synthesis of osteocalcin, a protein that is essential for the bones. However, osteocalcin is only active if it is modified by carboxylation, an enzymatic step that requires vitamin K. This may explain why long-term supplementation with either vitamin D,, or vitamin K,,,, can help reduce the risk of osteoporosis, falling, and/or fractures.
Because they have different mechanism of action, a combination of vitamins D and K might be expected to have synergistic effects, and this has now been confirmed. In controlled trials, supplementation with vitamins D3 (cholecalciferol) and K2 (menaquinone), together with calcium, was found to be far more effective in reducing postmenopausal bone loss and fracture risk than with either vitamin alone.,,, One study showed that daily supplementation with 800 IU of vitamin D3, 45 mcg of vitamin K2, and 1,200 mg of calcium reduced the lifetime fracture risk by 25%.
Menaquinone-7 (MK-7) is more bioavailable than other supplemental vitamin K forms, such as MK-4 or phylloquinone., Natto (fermented soy), a traditional Japanese food, is an excellent source of MK-7. Interestingly, Japanese men and women who consume natto have significantly higher BMDs than the population at large.
Vitamin E, another fat-soluble vitamin, also supports bone health. A study done in China showed a positive relationship between BMD and α-tocopherol (a form of vitamin E) levels. Tocotrienols, members of the vitamin E family that were discovered more recently, may be particularly effective for bone health and also have strong antioxidant properties.,, Tocotrienols improve bone health and reduce bone loss by stimulating osteoblasts, the cells that make bone, while at the same time inhibiting the formation of osteoclasts, the cells that break down bone.
Too little or too much vitamin A can also negatively impact bone health.,, Vegetarians often have low blood levels of vitamin A because fruits and vegetables only provide β-carotene, a vitamin A precursor, which is not always efficiently converted into retinol, the active form of vitamin A.,
Optimal BMDs are associated with moderate levels of vitamin A., When vitamin D levels are too low and vitamin A levels are too high, there may be an increase in the risk of osteoporosis., This effect goes away, however, when vitamin D is at normal levels. The potentially harmful effects of excess vitamin A may become apparent with prolonged daily intake of four times the recommended dietary allowance (RDA). The recommended intake of vitamin A for adults ranges between 700 and 900 mcg of retinol activity equivalents (RAE) per day, and the recommended upper limit (UL) for preformed vitamin A, such as retinyl palmitate, is 10,000 IU per day.
Fat-soluble vitamins and cardiovascular health
Adequate levels of vitamins D and K are thought to protect against hypertension and cardiovascular disease.
Adequate levels of vitamins D and K are thought to protect against hypertension and cardiovascular disease. ,, Vitamins D and K work together to form matrix Gla-protein (MGP), a potent inhibitor of arterial calcification, a process associated with atherosclerosis (the deposition of fat and plaques on the inner lining of the blood vessels) and heart attack. Ensuring adequacy of vitamins D and K may lower those risks. Indeed, in a three-year, double-blind, randomized controlled trial in older men and women, the individuals taking supplements containing calcium, vitamin D, and vitamin K had less coronary artery calcification than those taking calcium and vitamin D alone.
Diets high in vitamin E (tocopherols and tocotrienols) are associated with a lower risk for cardiovascular mortality than diets low in vitamin E., Tocotrienols help to reduce levels of harmful forms of cholesterol as well as its oxidation,, another factor which contributes to atherosclerosis and cardiovascular disease. They also help to reduce platelet aggregation (stickiness) and improve the function of the blood vessel walls.,, Vitamin A has positive effects on hearth health at sufficient moderate intakes, but levels that are either too low or too high can increase the risk for heart problems.,
Malabsorption of fat-soluble vitamins
The pancreas secretes lipase, an enzyme that is required for normal digestion and absorption of dietary fats, essential fatty acids, and fat-soluble vitamins.,,,, It’s perhaps not surprising, then, that malabsorption due to exocrine pancreatic insufficiency (EPI) leads to fat-soluble vitamin deficiencies.,,,,,
EPI is often treated with supplemental digestive enzymes (pancreatic enzyme replacement therapy, or PERT). Chronic pancreatitis is the most well-known cause of EPI, but the condition can also occur in individuals with cystic fibrosis; weight loss surgery; irritable bowel syndrome (IBS); diabetes or metabolic syndrome;, celiac disease;,,, and inflammatory bowel disease (ulcerative colitis and Crohn’s)., Because fat-soluble vitamin deficiencies increase the risk of osteoporosis,, individuals with EPI may benefit from vitamin supplementation.,,
The prevalence of EPI increases with age, even in apparently healthy individuals.,, Importantly, EPI may be more common than previously thought. About 20% of individuals over age 60 with no history of a gastrointestinal disorder or surgery have evidence of EPI. Although it is possible to detect mild changes in pancreatic exocrine function with early pancreatic disease, overt maldigestion of fat and protein does not occur until approximately 90% of pancreas exocrine function has been lost. Symptoms of mild EPI can include bloating, cramping, increased flatulence, and diarrhea, much like IBS.
The most common fat-soluble vitamin deficiency is that of vitamin D, followed by vitamin K. Deficiencies of vitamins D and K are associated with osteoporosis and cardiovascular disease. The only way to assure you are getting enough vitamin D is to have your levels tested via blood testing. Conditions associated with so a low vitamin D level could be an indicator of a broader nutritional problem. Although supplementation with vitamin A alone should be avoided as it can exacerbate the effects of low vitamin D, moderate, balanced levels of all the fat-soluble vitamins provide the most sensible approach.Click here to see References
 Borel P. Factors affecting intestinal absorption of highly lipophilic food microconstituents (fat-soluble vitamins, carotenoids and phytosterols). Clin Chem Lab Med. 2003;41(8):979-94.
 Harshman SG, et al. Mixed dishes are a top contributor to vitamin K Intake in US adults: data from the 2011-2012 NHANES. The FASEB Journal. 2017 Apr;31(1_supplement):648-12.
 Waniek S, et al. Vitamin E (α- and γ-tocopherol) levels in the community: distribution, clinical and biochemical correlates, and association with dietary patterns. Nutrients. 2017 Dec 21;10(1):3.
 Holick MF. The vitamin D deficiency pandemic: approaches for diagnosis, treatment and prevention. Rev Endocr Metab Disord. 2017 Jun;18(2):153-65.
 Riphagen IJ, et al. Prevalence and effects of functional vitamin K insufficiency: the PREVEND Study. Nutrients. 2017 Dec 8;9(12):1334.
 Torbergsen AC, et al. Vitamin K1 and 25(OH)D are independently and synergistically associated with a risk for hip fracture in an elderly population: a case control study. Clin Nutr. 2015 Feb;34(1):101-6.
 Lanham-New SA. Importance of calcium, vitamin D and vitamin K for osteoporosis prevention and treatment. Proc Nutr Soc. 2008 May;67(2):163-76.
 van Ballegooijen AJ, et al. The synergistic interplay between vitamins D and K for bone and cardiovascular health: a narrative review. Int J Endocrinol. 2017;2017:7454376.
 Fujita Y, et al. Association between vitamin K intake from fermented soybeans, natto, and bone mineral density in elderly Japanese men: the Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) study. Osteoporos Int. 2012 Feb;23(2):705-14.
 Fusaro M, et al. Vitamin K and bone. Clin Cases Miner Bone Metab. 2017 May-Aug;14(2):200-6.
 Yamaguchi M. Regulatory mechanism of food factors in bone metabolism and prevention of osteoporosis. Yakugaku Zasshi. 2006 Nov;126(11):1117-37.
 Poon CC, et al. In vitro vitamin K(2) and 1α,25-dihydroxyvitamin D(3) combination enhances osteoblasts anabolism of diabetic mice. Eur J Pharmacol. 2015 Nov 15;767:30-40.
 Rivera-Leon EA, et al. Vitamin-D receptor gene polymorphisms (TaqI and ApaI) and circulating osteocalcin in type 2 diabetic patients and healthy subjects. Endokrynol Pol. 2015;66(4):329-33.
 Bischoff-Ferrari HA, et al. Fall prevention with supplemental and active forms of vitamin D: a meta-analysis of randomized controlled trials. BMJ. 2009 Oct 1;339:b3692.
 Christakos S, et al. Vitamin D: metabolism, molecular mechanism of action, and pleiotropic effects. Physiol Rev. 2016 Jan;96(1):365-408.
 Cockayne S, et al. Vitamin K and the prevention of fractures: systematic review and meta-analysis of randomized controlled trials. Arch Intern Med. 2006 Jun 26;166(12):1256-61.
 Braam LA, et al. Vitamin K1 supplementation retards bone loss in postmenopausal women between 50 and 60 years of age. Calcif Tissue Int. 2003 Jul;73(1):21-6.
 Cheung AM, et al. Vitamin K supplementation in postmenopausal women with osteopenia (ECKO trial): a randomized controlled trial. PLoS Med. 2008 Oct 14;5(10):e196.
 Knapen MH, et al. Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women. Osteoporos Int. 2013 Sep;24(9):2499-507.
 Ushiroyama T, et al. Effect of continuous combined therapy with vitamin K(2) and vitamin D(3) on bone mineral density and coagulofibrinolysis function in postmenopausal women. Maturitas. 2002 Mar 25;41(3):211-21.
 Iwamoto J, et al. Effect of combined administration of vitamin D3 and vitamin K2 on bone mineral density of the lumbar spine in postmenopausal women with osteoporosis. J Orthop Sci. 2000;5(6):546-51.
 Bolton-Smith C, et al. Two-year randomized controlled trial of vitamin K1 (phylloquinone) and vitamin D3 plus calcium on the bone health of older women. J Bone Miner Res. 2007 Apr;22(4):509-19.
 Je SH, et al. Vitamin K supplement along with vitamin D and calcium reduced serum concentration of undercarboxylated osteocalcin while increasing bone mineral density in Korean postmenopausal women over sixty-years-old. J Korean Med Sci. 2011 Aug;26(8):1093-8.
 Gajic-Veljanoski O, et al. Vitamin K supplementation for the primary prevention of osteoporotic fractures: is it cost-effective and is future research warranted? Osteoporos Int. 2012 Nov;23(11):2681-92.
 Sato T, et al. Comparison of menaquinone-4 and menaquinone-7 bioavailability in healthy women. Nutr J. 2012 Nov 12;11:93.
 Schurgers LJ, et al. Vitamin K-containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7. Blood. 2007 Apr 15;109(8):3279-83.
 Shi WQ, et al. Association of dietary and serum vitamin E with bone mineral density in middle-aged and elderly Chinese adults: a cross-sectional study. Br J Nutr. 2016 Jan 14;115(1):113-20.
 Chin KY, Ima-Nirwana S. The biological effects of tocotrienol on bone: a review on evidence from rodent models. Drug Des Devel Ther. 2015 Apr 8;9:2049-61.
 Chin KY, et al. The effects of tocotrienol and lovastatin co-supplementation on bone dynamic histomorphometry and bone morphogenetic protein-2 expression in rats with estrogen deficiency. Nutrients. 2017 Feb 15;9(2):143.
 Ramanathan N, et al. Tocotrienol is a cardioprotective agent against aging-associated cardiovascular disease and its associated morbidities. Adv Nutr. 2017 Jan 17;8(1):27-39.
 Wan Hasan WN, et al. Annatto-derived tocotrienol stimulates osteogenic activity in preosteoblastic MC3T3-E1 cells: a temporal sequential study. Drug Des Devel Ther. 2018 Jun 13;12:1715-26.
 Radzi NFM, et al. Tocotrienols regulate bone loss through suppression on osteoclast differentiation and activity: a systematic review. Curr Drug Targets. 2018;19(9):1095-107.
 Chen GD, et al. Association of dietary consumption and serum levels of vitamin A and β-carotene with bone mineral density in Chinese adults. Bone. 2015 Oct;79:110-5.
 Hayhoe RPG, et al. Carotenoid dietary intakes and plasma concentrations are associated with heel bone ultrasound attenuation and osteoporotic fracture risk in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk cohort. Br J Nutr. 2017 May;117(10):1439-53.
 Xu J, et al. Carotenoids and risk of fracture: a meta-analysis of observational studies. Oncotarget. 2017 Jan 10;8(2):2391-9.
 Leung WC, et al. Two common single nucleotide polymorphisms in the gene encoding beta-carotene 15,15′-monoxygenase alter beta-carotene metabolism in female volunteers. FASEB J. 2009 Apr;23(4):1041-53.
 Lietz G, et al. Single nucleotide polymorphisms upstream from the β-carotene 15,15′-monoxygenase gene influence provitamin A conversion efficiency in female volunteers. J Nutr. 2012 Jan;142(1):161S-5S.
 Joo NS, et al. Vitamin A intake, serum vitamin D and bone mineral density: analysis of the Korea National Health and Nutrition Examination Survey (KNHANES, 2008-2011). Nutrients. 2015 Mar 10;7(3):1716-27.
 Mata-Granados JM, et al. Vitamin D insufficiency together with high serum levels of vitamin A increases the risk for osteoporosis in postmenopausal women. Arch Osteoporos. 2013;8:124.
 Lionikaite V, et al. Clinically relevant doses of vitamin A decrease cortical bone mass in mice. J Endocrinol. 2018 Oct 31;239(3):389-402.
 National Institutes of Health, Office of Dietary Supplements. Vitamin A Fact Sheet for Consumers [Internet]. Bethesda (MD): US Department of Health and Human Services; 2013 [cited 2018 November 20]. Available from: https://ods.od.nih.gov/factsheets/VitaminA-Consumer/
 Mirhosseini N, et al. Vitamin D Supplementation, serum 25(OH)D concentrations and cardiovascular disease risk factors: a systematic review and meta-analysis. Front Cardiovasc Med. 2018 Jul 12;5:87.
 Ginde AA, et al. Prospective study of serum 25-hydroxyvitamin D level, cardiovascular disease mortality, and all-cause mortality in older U.S. adults. J Am Geriatr Soc. 2009 Sep;57(9):1595-603.
 Ballegooijen AJ, et al. Joint association of low vitamin D and vitamin K status with blood pressure and hypertension. Hypertension. 2017;69:1165-72.
 Schurgers LJ, et al. Matrix Gla-protein: the calcification inhibitor in need of vitamin K. Thromb Haemost. 2008 Oct;100(4):593-603.
 Liu W, et al. Current understanding of coronary artery calcification. J Geriatr Cardiol. 2015 Nov;12(6):668-75.
 Shea MK, et al. Vitamin K supplementation and progression of coronary artery calcium in older men and women. Am J Clin Nutr. 2009 Jun;89(6):1799-807.
 Schwingshackl L, et al. Dietary supplements and risk of cause-specific death, cardiovascular disease, and cancer: a systematic review and meta-analysis of primary prevention trials. Adv Nutr. 2017 Jan 17;8(1):27-39.
 Rizvi S, et al. The role of vitamin E in human health and some diseases. Sultan Qaboos Univ Med J. 2014 May;14(2):e157-65.
 Qureshi AA, et al. Impact of delta-tocotrienol on inflammatory biomarkers and oxidative stress in hypercholesterolemic subjects. Clin Exp Cardiology. 2015;6(4):1000367.
 Qureshi AA, et al. Dose-dependent modulation of lipid parameters, cytokines, and RNA by delta-tocotrienol in hypercholesterolemic subjects restricted to AHA Step-1 diet. Brit J of Med & Med Res. 2015;6(4):351-66.
 Qureshi AA, et al. Tocotrienols-induced inhibition of platelet thrombus formation and platelet aggregation in stenosed canine coronary arteries. Lipids Health Dis. 2011;10:58.
 Rahman TA, et al. Atheroprotective effects of pure tocotrienol supplementation in the treatment of rabbits with experimentally induced early and established atherosclerosis. Food Nutr Res. 2016;60:31525.
 Rasool AH, et al. Arterial compliance and vitamin E blood levels with a self-emulsifying preparation of tocotrienol rich vitamin E. Arch Pharm Res. 2008 Sep;31(9):1212-7.
 Lima IOL, et al. Association of ischemic cardiovascular disease with inadequacy of liver store of retinol in elderly individuals. Oxid Med Cell Longev. 2018 Apr 2;2018:9785231.
 Olsen T, et al. The risk association of plasma total homocysteine with acute myocardial infarction is modified by serum vitamin A. Eur J Prev Cardiol. 2018 Oct;25(15):1612-20.
 Loli H, et al. Lipases in medicine: an overview. Mini Rev Med Chem. 2015;15(14):1209-16.
 Shearer MJ, et al. Vitamin K nutrition, metabolism, and requirements: current concepts and future research. Adv Nutr. 2012 Mar 1;3(2):182-95.
 Benage D, O’Connor KW. Cholecystocolonic fistula: malabsorptive consequences of lost bile acids. J Clin Gastroenterol. 1990 Apr;12(2):192-4.
 Saeed A, et al. Disturbed vitamin A metabolism in non-alcoholic fatty liver disease (NAFLD). Nutrients. 2017 Dec 29;10(1):29.
 Botella-Carretero JI, et al. Retinol and alpha-tocopherol in morbid obesity and nonalcoholic fatty liver disease. Obes Surg. 2010 Jan;20(1):69-76.
 Singh VK, et al. Less common etiologies of exocrine pancreatic insufficiency. World J Gastroenterol. 2017 Oct 21;23(39):7059-76.
 Martínez-Moneo E, et al. Deficiency of fat-soluble vitamins in chronic pancreatitis: a systematic review and meta-analysis. Pancreatology. 2016 Nov-Dec;16(6):988-94.
 Stigliano S, et al. Vitamins D and K as factors associated with osteopathy in chronic pancreatitis: a prospective multicentre study (P-BONE Study). Clin Transl Gastroenterol. 2018 Oct 15;9(10):197.
 Othman MO, et al. Introduction and practical approach to exocrine pancreatic insufficiency for the practicing clinician. Int J Clin Pract. 2018 Feb;72(2).
 Bonifant CM, et al. Vitamin A supplementation for cystic fibrosis. Cochrane Database Syst Rev. 2014 May 14;(5):CD006751.
 Sikkens EC, et al. The prevalence of fat-soluble vitamin deficiencies and a decreased bone mass in patients with chronic pancreatitis. Pancreatology. 2013 May-Jun;13(3):238-42.
 Sherf Dagan S, et al. Nutritional recommendations for adult bariatric surgery patients: clinical practice. Adv Nutr. 2017 Mar 15;8(2):382-94.
 Leeds JS, et al. Some patients with irritable bowel syndrome may have exocrine pancreatic insufficiency. Clin Gastroenterol Hepatol. 2010 May;8(5):433-8.
 Piciucchi M, et al. Exocrine pancreatic insufficiency in diabetic patients: prevalence, mechanisms, and treatment. Int J Endocrinol. 2015;2015:595649.
 Godala M, et al. The risk of plasma vitamin A, C, E and D deficiency in patients with metabolic syndrome: A case-control study. Adv Clin Exp Med. 2017 Jul;26(4):581-6.
 Farnetti S, et al. Functional and metabolic disorders in celiac disease: new implications for nutritional treatment. J Med Food. 2014 Nov;17(11):1159-64.
 Leeds JS, et al. Is exocrine pancreatic insufficiency in adult celiac disease a cause of persisting symptoms? Aliment Pharmacol Ther. 2007 Feb 1;25(3):265-71.
 Mager DR, et al. Vitamin D and K status influences bone mineral density and bone accrual in children and adolescents with celiac disease. Eur J Clin Nutr. 2012 Apr;66(4):488-95.
 Romańczuk B, et al. Analysis of the concentration of vitamin E in erythrocytes of patients with celiac disease. Prz Gastroenterol. 2016;11(4):282-5.
 Pitchumoni CS, et al. Pancreatitis in inflammatory bowel diseases. J Clin Gastroenterol. 2010 Apr;44(4):246-53.
 Fabisiak N, et al. Fat-soluble vitamin deficiencies and inflammatory bowel disease: systematic review and meta-analysis. J Clin Gastroenterol. 2017 Nov/Dec;51(10):878-89.
 Czymczak J, et al. Low bone mineral density in adult patients with celiac disease. Endokrynol Pol. 2012;63(4):270-6.
 Rothenbacher D, et al. Prevalence and determinants of exocrine pancreatic insufficiency among older adults: results of a population-based study. Scand J Gastroenterol. 2005 Jun;40(6):697-704.
 Laugier R, et al. Changes in pancreatic exocrine secretion with age: pancreatic exocrine secretion does decrease in the elderly. Digestion. 1991;50(3-4):202-11.
 Campbell JA, et al. PWE-208 How common is pancreatic exocrine insufficiency in primary care? Gut 2015;64:A303.
 Herzig KH, et al. Fecal pancreatic elastase-1 levels in older individuals without known gastrointestinal diseases or diabetes mellitus. BMC Geriatr. 2011 Jan 25;11:4.
 DiMagno EP, et al. Relations between pancreatic enzyme ouputs and malabsorption in severe pancreatic insufficiency. N Engl J Med. 1973 Apr 19;288(16):813-5.
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Marina MacDonald, MS, PhD
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