Fat- and water-soluble vitamins

Which vitamins are fat-soluble and which are water-soluble?

According to the Merck Manual, the fat-soluble vitamins are A, D, E, and K; the water-soluble ones are the B vitamins and vitamin C. The B vitamins include biotin, folate, niacin, pantothenic acid, riboflavin, thiamin, B6, and B12. ^[1]

Guides for the four fat-soluble vitamins: vitamin A, vitamin D, vitamin E, and vitamin K (K2). Guides for the water-soluble ones: vitamin C, B12, B6, B1, folic acid, biotin, and for all eight B vitamins B complex. The function, source, and deficiency disease of all vitamins are in the table on the Types of vitamins page.

What does solubility change?

Fat-soluble vitamins are also absorbed in the intestine together with dietary fat; their excess is excreted mainly through bile in the feces, and part of A and E and a small part of D in urine. ^{[2] [2]}

Do fat-soluble vitamins really accumulate in the body?

Fat-soluble vitamins are stored in the liver; the excess of the vitamin is excreted mainly through bile in the feces. ^[2] Storage has two consequences. The first is that when intake is inadequate, deficiency appears late; the Merck Manual reports this as more than a year. ^[1] Vitamin K is the exception to this generalization: according to the NIH, compared with the other fat-soluble vitamins, vitamin K is rapidly broken down and excreted, is present in very small amounts in the blood, and its tissue stores are relatively low. Deficiency can be seen in the first weeks of life (vitamin K deficiency bleeding in newborns); in adults clinically meaningful deficiency is very rare and is generally limited to people with malabsorption or those using medicines that affect vitamin K metabolism. ^[9] The second is that toxicity is possible when high doses are taken for a long time.

According to the Merck Manual’s table, excess vitamin A can cause headache, skin peeling, enlargement of the liver and spleen, bone thickening, increased intracranial pressure, papilledema, and hypercalcemia; excess vitamin D can cause hypercalcemia, loss of appetite, kidney failure, and metastatic calcifications; and excess vitamin E can cause a bleeding tendency. ^[1] The review in J Clin Med reports that hypervitaminosis can occur especially with fat-soluble vitamins through long-term high-dose supplements, vitamin-fortified foods, and hidden sources in supplements. The same review states that the symptoms of vitamin D excess are due to high calcium (weakness, loss of appetite, weight loss, digestive disturbances, and neurological findings such as headache and vomiting). ^[2] Vitamin D excess from supplements and upper limits are covered separately in the vitamin D excess guide.

Among fat-soluble vitamins, too, the picture differs for each vitamin: no upper limit has been set for vitamin K in either the US or EFSA. ^{[1] [8]} EFSA sets upper limits for vitamins A, D, and E (3,000 µg RE for preformed A, 100 µg for D, and 300 mg for E, respectively), while review of the vitamin E limit is ongoing. ^[8]

Detailed guideVitamin A: reference intake, high-dose risk in pregnancy, and beta-carotene warning→ Detailed guideVitamin D: reference intake, upper limit, testing, and evidence for supplements→

Is the excess of water-soluble vitamins safe?

No, not always. The claim “the excess is excreted in urine” may be true for some water-soluble vitamins; however, the Merck Manual states that vitamin toxicity mostly results from megadoses of A, D, C, B6, or niacin; three of these (C, B6, and niacin) are water-soluble. ^[1] In the table, the toxicity of vitamin C appears as hyperoxaluria, of niacin as flushing, and of B6 as peripheral neuropathy. ^[1]

The B6 example: a water-soluble vitamin that can cause nerve damage

According to EFSA’s 2023 assessment of B6, the relationship between excess B6 intake and the development of peripheral neuropathy is well established, and the upper limit is built on this effect. The lowest observed adverse effect level (LOAEL) could not be identified from human data; a reference point of 50 mg/day was determined from a case-control study, supported by case reports and pharmacovigilance data. An uncertainty factor of 4 was applied and, combined with the value calculated from dog data, the upper limit for adults (including pregnant and lactating women) was set at 12 mg/day. ^[6] EFSA reports that it is unlikely that the EU population exceeds the upper limit, while those who regularly use food supplements containing high-dose B6 are outside this. ^[6]

The systematic review published in Nutrients (20 articles) supports the same direction: when B6 levels rise, generally after food supplements, an axonal neuropathy that is predominantly or exclusively of the sensory type can develop; after pyridoxine is stopped, these patients report improvement in their complaints. The same review says that low B6 levels can be seen together with neuropathy but that there is no robust evidence of a direct causal role for low B6. ^[7] Detailed information, the upper limit difference (US 100 mg, EFSA 12 mg), and in whom caution is needed are in the B6 guide.

Detailed guideVitamin B6: deficiency, neuropathy, and the upper limit difference→

Should vitamins be taken with a meal? What does timing do?

According to the J Clin Med review, vitamins A, D, E, and K are absorbed in the intestine together with dietary fat; conditions that impair fat absorption (celiac disease, Crohn’s disease, small bowel resection, chronic pancreatitis, cystic fibrosis, bile salt problems) and liver diseases increase the risk of fat-soluble vitamin deficiency. ^[2]

The effect of fat on absorption is not the same for every vitamin. According to Borel’s review, the metabolism of fat-soluble vitamins and carotenoids (highly lipophilic food microconstituents) in the upper digestive tract varies by compound; some are absorbed by passive diffusion, others by a transporter; the molecular form of the compound, fat in the food, and the food matrix affect the absorption of most compounds, while other factors such as fiber affect only some. The review also notes that there are knowledge gaps in this area. ^[3]

The measured results for vitamin D are mixed: in a single-dose study, absorption was higher with a fatty meal, whereas in a 90-day follow-up, blood 25(OH)D level was not found to differ by meal conditions. Details are in the “When to take vitamin D?” guide. Timing questions for other vitamins are also in the relevant guides.

Detailed guideWhen to take vitamin D? Meals, morning-evening, and intermittent use→ Detailed guideWhen to take vitamin C?→ Detailed guideWhen to take magnesium?→

How much do cooking and storage reduce vitamins?

The two-part review by Rickman and colleagues examines changes in nutrients in fresh, frozen, and canned fruits and vegetables. According to the first part, nutrient loss during storage and cooking in fresh products can be more pronounced than generally thought. In canned and frozen products, the initial heat treatment can cause loss in water-soluble and oxygen-sensitive vitamin C and B vitamins; in canned products these nutrients are relatively stable during later storage because there is no oxygen, whereas in frozen ones the initial loss is small but more is lost by oxidation during storage. The review also notes that changes in moisture content can misrepresent nutrient changes and that recommendations for fresh produce only disregard the nutritional benefit of canned and frozen products. ^[4]

According to the second part, carotenoids, vitamin E, minerals, and fiber are generally similar in comparable fresh and processed products (it is also noted that there are few studies for vitamin E); minerals and fiber are generally resistant to processing, storage, and cooking but can be lost in steps such as peeling. The review also reports that nutrient content varies significantly with the product, variety, and post-harvest handling. ^[5] These reviews cover fruits and vegetables; since losses vary greatly by food, variety, and method, a single rate cannot be given.

In which situations does the solubility difference matter?

• Diseases that impair fat absorption: Celiac disease, Crohn’s disease, chronic pancreatitis, cystic fibrosis, short bowel syndrome, and bile salt disorders increase the risk of fat-soluble vitamin deficiency. ^[2] The symptoms of vitamin A and E deficiencies and in whom they are seen are described on the relevant pages: vitamin A deficiency and vitamin E deficiency symptoms.
• Long-term, high-amount supplementation: Regardless of solubility, megadoses of A, D, C, B6, and niacin draw attention for toxicity. ^[1]
• General risk of deficiency: Because for water-soluble vitamins (except B12) deficiency can develop within weeks to months, it appears early in inadequate nutrition. ^[1]

Detailed guideVitamin deficiency symptoms: which complaint is related to which vitamin?→ Detailed guideWhat are vitamins? Daily requirement, label reading, and supplements→

This guide does not recommend personal doses; the solubility difference is not on its own a criterion for whether a vitamin is safe or unsafe.