Healthy AgingVitamin Mineral Research

The Fat-Soluble Vitamins: A, D, E and K

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.[1] Fatty fish, vegetable oils, green vegetables, and nuts and seeds are good sources of vitamins A, D, E, and K, collectively.[2],[3] 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.[4],[5],[6],[7],[8]

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.[4] 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.[5] 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, which increases the risk of osteoporosis, falling, and bone fractures with age.

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.[9],[10],[11] 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.[6]

We now know that vitamins D and K work together to keep bones healthy.[12] Vitamin D increases the synthesis of osteocalcin,[13] 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.[8] This may explain why long-term supplementation with either vitamin D,[14],[15] or vitamin K,[16],[17],[18],[19] 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.[20],[21],[22],[23] 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%.[24]

Menaquinone-7 (MK-7) is more bioavailable than other supplemental vitamin K forms, such as MK-4 or phylloquinone.[25],[26] 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.[12]

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.[27] 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.[28],[29],[30] Tocotrienols improve bone health and reduce bone loss by stimulating osteoblasts, the cells that make bone,[31] while at the same time inhibiting the formation of osteoclasts, the cells that break down bone.[32]

Too little or too much vitamin A can also negatively impact bone health.[33],[34],[35] 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.[36],[37]

Optimal BMDs are associated with moderate levels of vitamin A.[38],[39] When vitamin D levels are too low and vitamin A levels are too high, there may be an increase in the risk of osteoporosis.[38],[39] 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).[40] 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.[41]

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. [42],[43],[44] 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.[45] Ensuring adequacy of vitamins D and K may lower those risks.[46] 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.[47]

Diets high in vitamin E (tocopherols and tocotrienols) are associated with a lower risk for cardiovascular mortality than diets low in vitamin E.[48],[49] Tocotrienols help to reduce levels of harmful forms of cholesterol as well as its oxidation,[50],[51] 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.[52],[53],[54] 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.[55],[56]

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.[57],[58],[59],[60],[61] It’s perhaps not surprising, then, that malabsorption due to exocrine pancreatic insufficiency (EPI) leads to fat-soluble vitamin deficiencies.[62],[63],[64],[65],[66],[67]

EPI is often treated with supplemental digestive enzymes (pancreatic enzyme replacement therapy, or PERT).[60] Chronic pancreatitis is the most well-known cause of EPI,[57] but the condition can also occur in individuals with cystic fibrosis; weight loss surgery;[68] irritable bowel syndrome (IBS);[69] diabetes or metabolic syndrome;[70],[71] celiac disease;[72],[73],[74],[75] and inflammatory bowel disease (ulcerative colitis and Crohn’s).[76],[77] Because fat-soluble vitamin deficiencies increase the risk of osteoporosis,[68],[78] individuals with EPI may benefit from vitamin supplementation.[59],[60],[62]

The prevalence of EPI increases with age, even in apparently healthy individuals.[74],[79],[80] Importantly, EPI may be more common than previously thought.[81] About 20% of individuals over age 60 with no history of a gastrointestinal disorder or surgery have evidence of EPI.[82] 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.[83] 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.

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