de Botton, S., Coiteux, V., Chevret, S., Rayon, C., Vilmer, E., Sanz, M., de La, Serna J., Philippe, N., Baruchel, A., Leverger, G., Robert, A., San, Miguel J., Conde, E., Sotto, J. J., Bordessoule, D., Fegueux, N., Fey, M., Parry, A., Chomienne, C., Degos, L., and Fenaux, P. Outcome of childhood acute promyelocytic leukemia with all-trans-retinoic acid and chemotherapy. J Clin.Oncol. 4-15-2004;22(8):1404-1412. View abstract.

Finklestein, J. Z., Krailo, M. D., Lenarsky, C., Ladisch, S., Blair, G. K., Reynolds, C. P., Sitarz, A. L., and Hammond, G. D. 13-cis-retinoic acid (NSC 122758) in the treatment of children with metastatic neuroblastoma unresponsive to conventional chemotherapy: report from the Childrens Cancer Study Group. Med.Pediatr.Oncol. 1992;20(4):307-311. View abstract.

In developed countries, the amounts of vitamin A in breast milk are sufficient to meet infants' needs for the first 6 months of life. But in women with vitamin A deficiency, breast milk volume and vitamin A content are suboptimal and not sufficient to maintain adequate vitamin A stores in infants who are exclusively breastfed [19]. The prevalence of vitamin A deficiency in developing countries begins to increase in young children just after they stop breastfeeding [3]. The most common and readily recognized symptom of vitamin A deficiency in infants and children is xerophthalmia.


Maraini, G., Williams, S. L., Sperduto, R. D., Ferris, F., Milton, R. C., Clemons, T. E., Rosmini, F., and Ferrigno, L. A randomized, double-masked, placebo-controlled clinical trial of multivitamin supplementation for age-related lens opacities. Clinical trial of nutritional supplements and age-related cataract report no. 3. Ophthalmology 2008;115(4):599-607. View abstract.

A meta-analysis from 2015 reported that for studies which reported serum tocopherol, higher serum concentration was associated with a 23% reduction in relative risk of age-related cataracts (ARC), with the effect due to differences in nuclear cataract rather than cortical or posterior subcapsular cataract - the three major classifications of age-related cataracts.[94] However, this article and a second meta-analysis reporting on clinical trials of alpha-tocopherol supplementation reported no statistically significant change to risk of ARC when compared to placebo.[94][95]

Most people meet at least some of their vitamin D needs through exposure to sunlight [1,2]. Ultraviolet (UV) B radiation with a wavelength of 290–320 nanometers penetrates uncovered skin and converts cutaneous 7-dehydrocholesterol to previtamin D3, which in turn becomes vitamin D3 [1]. Season, time of day, length of day, cloud cover, smog, skin melanin content, and sunscreen are among the factors that affect UV radiation exposure and vitamin D synthesis [1]. Perhaps surprisingly, geographic latitude does not consistently predict average serum 25(OH)D levels in a population. Ample opportunities exist to form vitamin D (and store it in the liver and fat) from exposure to sunlight during the spring, summer, and fall months even in the far north latitudes [1].

^ Jump up to: a b c d e Péter S, Friedel A, Roos FF, Wyss A, Eggersdorfer M, Hoffmann K, Weber P (December 2015). "A Systematic Review of Global Alpha-Tocopherol Status as Assessed by Nutritional Intake Levels and Blood Serum Concentrations". International Journal for Vitamin and Nutrition Research. Internationale Zeitschrift Fur Vitamin- und Ernahrungsforschung. Journal International de Vitaminologie et de Nutrition. 85 (5–6): 261–281. doi:10.1024/0300-9831/a000281. PMID 27414419.
The Age-Related Eye Disease Study (AREDS), a large randomized clinical trial, found that participants at high risk of developing advanced AMD (i.e., those with intermediate AMD or those with advanced AMD in one eye) reduced their risk of developing advanced AMD by 25% by taking a daily supplement containing beta-carotene (15 mg), vitamin E (400 IU dl-alpha-tocopheryl acetate), vitamin C (500 mg), zinc (80 mg), and copper (2 mg) for 5 years compared to participants taking a placebo [32].
^ Jump up to: a b Fortmann SP, Burda BU, Senger CA, Lin JS, Whitlock EP (2013). "Vitamin and mineral supplements in the primary prevention of cardiovascular disease and cancer: An updated systematic evidence review for the U.S. Preventive Services Task Force". Annals of Internal Medicine. 159 (12): 824–834. doi:10.7326/0003-4819-159-12-201312170-00729. PMID 24217421.

For the conditions described below, the results of RCTs do not always concur with the observational evidence. This could be a matter of amount. Observational studies compare low consumers to high consumers based on intake from food, whereas RCTS often used amounts of alpha-tocopherol 20X to 30X higher than what can be achieved from food. Diets higher in vitamin E may contain other compounds that convey health benefits, so the observed effect may not be due to the vitamin E content. There is also a concern that supplementing with alpha-tocopherol in multiples much higher than is possible via diet will suppress absorption and retention of other tocopherols, with unknown effects on health. Supplementing alpha-tocopherol is known to reduced serum gamma- and delta-tocopherol concentrations.[63] From one large survey, consumption of alpha-tocopherol as a supplement lowered serum gamma-tocopherol from 6.0 micromol/L for people not consuming any supplement to 2.1 micromol/L for those consuming greater than or equal to 400 IU/day.[64]
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Tocotrienols and tocopherols, the latter including the stereoisomers of synthetic alpha-tocopherol, are absorbed from the intestinal lumen, incorporated into chylomicrons, and secreted into the portal vein, leading to the liver. Absorption efficiency is estimated at 51% to 86%,[2] and that applies to all of the vitamin E family–there is no discrimination among the vitamin E vitamers during absorption. Unabsorbed vitamin E is excreted via feces. Additionally, vitamin E is excreted by the liver via bile into the intestinal lumin, where it will either be reabsorbed or excreted via feces, and all of the vitamin E vitamers are metabolized and then excreted via urine.[2][37]
The body needs vitamin A to maintain the corneas and other epithelial surfaces, so the lower serum concentrations of vitamin A associated with measles, especially in people with protein-calorie malnutrition, can lead to blindness. None of the studies evaluated in a Cochrane review evaluated blindness as a primary outcome [36]. However, a careful clinical investigation of 130 African children with measles revealed that half of all corneal ulcers in these children, and nearly all bilateral blindness, occurred in those with vitamin A deficiency [37].

Pregnancy and breast-feeding: Vitamin A is LIKELY SAFE for pregnant or breast-feeding women when taken in recommended amounts of less than 10,000 IU per day. Larger amounts are POSSIBLY UNSAFE. Vitamin A can cause birth defects. It is especially important for pregnant women to monitor their intake of vitamin A from all sources during the first three months of pregnancy. Forms of vitamin A are found in several foods including animal products, primarily liver, some fortified breakfast cereals, and dietary supplements.
There is an observed inverse correlation seen with dietary vitamin E, but no confirming evidence from placebo-controlled clinical trials. A meta-analysis published in 2005 concluded that diets higher in vitamin E content lowered risk of developing Parkinson's disease.[107] From what appears to be the only clinical trial of tocopherol supplementation in people with early Parkinson's disease, 2000 IU/day for 14 months had no effect on rate of disease progression.[108]
Alpha-tocopherol transfer protein is coded by the TTPA gene on chromosome 8. The binding site for RRR-α-tocopherol is a hydrophobic pocket with a lower affinity for beta-, gamma-, or delta-tocopherols, or for the stereoisomers with an S configuration at the chiral 2 site. Tocotrienols are also a poor fit because the double bonds in the phytic tail create a rigid configuration that is a mismatch with the α-TTP pocket.[37] A rare genetic defect of the TTPA gene results in people exhibiting a progressive neurodegenerative disorder known as ataxia with vitamin E deficiency (AVED) despite consuming normal amounts of vitamin E. Large amounts of alpha-tocopherol as a dietary supplement are needed to compensate for the lack of α-TTP[18] The role of α-TTP is to move α-tocopherol to the plasma membrane of hepatocytes (liver cells), where in can be incorporated into newly created very low density lipoprotein (VLDL) molecules. These convey α-tocopherol to cells in the rest of the body. As an example of a result of the preferential treatment, the US diet delivers approximately 70 mg/d of γ-tocopherol and plasma concentrations are on the order of 2–5 µmol/L; meanwhile. dietary α-tocopherol is about 7 mg/d but plasma concentrations are in the range of 11–37 µmol/L.[37]
Raffoux, E., Rousselot, P., Poupon, J., Daniel, M. T., Cassinat, B., Delarue, R., Taksin, A. L., Rea, D., Buzyn, A., Tibi, A., Lebbe, G., Cimerman, P., Chomienne, C., Fermand, J. P., de, The H., Degos, L., Hermine, O., and Dombret, H. Combined treatment with arsenic trioxide and all-trans-retinoic acid in patients with relapsed acute promyelocytic leukemia. J Clin.Oncol. 6-15-2003;21(12):2326-2334. View abstract.
The term vitamin was derived from "vitamine", a compound word coined in 1912 by the Polish biochemist Casimir Funk[69] when working at the Lister Institute of Preventive Medicine. The name is from vital and amine, meaning amine of life, because it was suggested in 1912 that the organic micronutrient food factors that prevent beriberi and perhaps other similar dietary-deficiency diseases might be chemical amines. This was true of thiamine, but after it was found that other such micronutrients were not amines the word was shortened to vitamin in English.

Hercberg, S., Preziosi, P., Galan, P., Faure, H., Arnaud, J., Duport, N., Malvy, D., Roussel, A. M., Briancon, S., and Favier, A. "The SU.VI.MAX Study": a primary prevention trial using nutritional doses of antioxidant vitamins and minerals in cardiovascular diseases and cancers. SUpplementation on VItamines et Mineraux AntioXydants. Food Chem.Toxicol. 1999;37(9-10):925-930. View abstract.
Lippman, S. M., Lee, J. J., Karp, D. D., Vokes, E. E., Benner, S. E., Goodman, G. E., Khuri, F. R., Marks, R., Winn, R. J., Fry, W., Graziano, S. L., Gandara, D. R., Okawara, G., Woodhouse, C. L., Williams, B., Perez, C., Kim, H. W., Lotan, R., Roth, J. A., and Hong, W. K. Randomized phase III intergroup trial of isotretinoin to prevent second primary tumors in stage I non-small-cell lung cancer. J Natl.Cancer Inst. 4-18-2001;93(8):605-618. View abstract.
Acosta, C. J., Galindo, C. M., Schellenberg, D., Aponte, J. J., Kahigwa, E., Urassa, H., Schellenberg, J. R., Masanja, H., Hayes, R., Kitua, A. Y., Lwilla, F., Mshinda, H., Menendez, C., Tanner, M., and Alonso, P. L. Evaluation of the SPf66 vaccine for malaria control when delivered through the EPI scheme in Tanzania. Trop.Med Int Health 1999;4(5):368-376. View abstract.
Furthermore, while serum 25(OH)D levels increase in response to increased vitamin D intake, the relationship is non-linear for reasons that are not entirely clear [1]. The increase varies, for example, by baseline serum levels and duration of supplementation. Increasing serum 25(OH)D to >50 nmol/L requires more vitamin D than increasing levels from a baseline <50 nmol/L. There is a steeper rise in serum 25(OH)D when the dose of vitamin D is <1,000 IU/day; a lower, more flattened response is seen at higher daily doses. When the dose is ≥1,000 IU/day, the rise in serum 25(OH)D is approximately 1 nmol/L for each 40 IU of intake. In studies with a dose ≤600 IU/day, the rise is serum 25(OH)D was approximately 2.3 nmol/L for each 40 IU of vitamin D consumed [1].

Ideo, G., Bellobuono, A., Tempini, S., Mondazzi, L., Airoldi, A., Benetti, G., Bissoli, F., Cestari, C., Colombo, E., Del, Poggio P., Fracassetti, O., Lazzaroni, S., Marelli, A., Paris, B., Prada, A., Rainer, E., and Roffi, L. Antioxidant drugs combined with alpha-interferon in chronic hepatitis C not responsive to alpha-interferon alone: a randomized, multicentre study. Eur J Gastroenterol Hepatol. 1999;11(11):1203-1207. View abstract.

A meta-analysis from 2015 reported that for studies which reported serum tocopherol, higher serum concentration was associated with a 23% reduction in relative risk of age-related cataracts (ARC), with the effect due to differences in nuclear cataract rather than cortical or posterior subcapsular cataract - the three major classifications of age-related cataracts.[94] However, this article and a second meta-analysis reporting on clinical trials of alpha-tocopherol supplementation reported no statistically significant change to risk of ARC when compared to placebo.[94][95]
Antioxidant vitamins as dietary supplements have been proposed as having benefits if consumed during pregnancy. For the combination of vitamin E with vitamin C supplemented to pregnant women, a Cochrane review concluded that the data do not support vitamin E supplementation - majority of trials alpha-tocopherol at 400 IU/day plus vitamin C at 1000 mg/day - as being efficacious for reducing risk of stillbirth, neonatal death, preterm birth, preeclampsia or any other maternal or infant outcomes, either in healthy women or those considered at risk for pregnancy complications.[109] The review identified only three small trials in which vitamin E was supplemented without co-supplementation with vitamin C. None of these trials reported any clinically meaningful information.[109]
The missing B vitamins were reclassified or determined not to be vitamins. For example, B9 is folic acid and five of the folates are in the range B11 through B16. Others, such as PABA (formerly B10), are biologically inactive, toxic, or with unclassifiable effects in humans, or not generally recognised as vitamins by science,[55] such as the highest-numbered, which some naturopath practitioners call B21 and B22. There are also nine lettered B complex vitamins (e.g., Bm). There are other D vitamins now recognised as other substances, which some sources of the same type number up to D7. The controversial cancer treatment laetrile was at one point lettered as vitamin B17. There appears to be no consensus on any vitamins Q, R, T, V, W, X, Y or Z, nor are there substances officially designated as vitamins N or I, although the latter may have been another form of one of the other vitamins or a known and named nutrient of another type.
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