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.
Most supplementation trials of the effects of vitamin D on bone health also include calcium, so it is difficult to isolate the effects of each nutrient. Among postmenopausal women and older men, supplements of both vitamin D and calcium result in small increases in bone mineral density throughout the skeleton. They also help to reduce fractures in institutionalized older populations, although the benefit is inconsistent in community-dwelling individuals [1,2,48]. Vitamin D supplementation alone appears to have no effect on risk reduction for fractures nor does it appear to reduce falls among the elderly [1,2,48]; one widely-cited meta-analysis suggesting a protective benefit of supplemental vitamin D against falls [49] has been severely critiqued [1]. However, a large study of women aged ≥69 years followed for an average of 4.5 years found both lower (<50 nmol/L [<20 ng/mL]) and higher(≥75 nmol/L [≥30 ng/mL]) 25(OH)D levels at baseline to be associated with a greater risk of frailty [50]. Women should consult their healthcare providers about their needs for vitamin D (and calcium) as part of an overall plan to prevent or treat osteoporosis.

Older adults are at increased risk of developing vitamin D insufficiency in part because, as they age, skin cannot synthesize vitamin D as efficiently, they are likely to spend more time indoors, and they may have inadequate intakes of the vitamin [1]. As many as half of older adults in the United States with hip fractures could have serum 25(OH)D levels <30 nmol/L (<12 ng/mL) [2].
HIV transmission. Taking vitamin A by mouth does not lower the risk of passing HIV to the fetus during pregnancy, to newborns during delivery, or to infants during breastfeeding. In fact, early research shows that HIV-positive women who take vitamin A supplements during pregnancy might have an increased risk of passing HIV to their babies through breast milk.
The FNB established an RDA for vitamin D representing a daily intake that is sufficient to maintain bone health and normal calcium metabolism in healthy people. RDAs for vitamin D are listed in both International Units (IUs) and micrograms (mcg); the biological activity of 40 IU is equal to 1 mcg (Table 2). Even though sunlight may be a major source of vitamin D for some, the vitamin D RDAs are set on the basis of minimal sun exposure [1].
For the most part, vitamins are obtained from the diet, but some are acquired by other means: for example, microorganisms in the gut flora produce vitamin K and biotin; and one form of vitamin D is synthesized in skin cells when they are exposed to a certain wavelength of ultraviolet light present in sunlight. Humans can produce some vitamins from precursors they consume: for example, vitamin A is synthesized from beta carotene; and niacin is synthesized from the amino acid tryptophan.[26] The Food Fortification Initiative lists countries which have mandatory fortification programs for vitamins folic acid, niacin, vitamin A and vitamins B1, B2 and B12.[4]
The U.S. Food and Nutrition Board set a Tolerable upper intake level (UL) at 1,000 mg (1,500 IU) per day derived from animal models that demonstrated bleeding at high doses.[2] The European Food Safety Authority reviewed the same safety question and set a UL at 300 mg/day.[23] A meta-analysis of long-term clinical trials reported a non-significant 2% increase in all-cause mortality when alpha-tocopherol was the only supplement used. The same meta-analysis reported a statistically significant 3% increase for results when alpha-tocopherol was used by itself or in combination with other nutrients (vitamin A, vitamin C, beta-carotene, selenium).[5] Another meta-analysis reported a non-significant 1% increase in all-cause mortality when alpha-tocopherol was the only supplement. Subset analysis reported no difference between natural (plant extracted) or synthetic alpha-tocopherol, or whether the amount used was less than or more than 400 IU/day.[24] There are reports of vitamin E-induced allergic contact dermatitis from use of vitamin-E derivatives such as tocopheryl linoleate and tocopherol acetate in skin care products. Incidence is low despite widespread use.[25]
Age-related macular degeneration (AMD) is a major cause of significant vision loss in older people. AMD's etiology is usually unknown, but the cumulative effect of oxidative stress is postulated to play a role. If so, supplements containing carotenoids with antioxidant functions, such as beta-carotene, lutein, and zeaxanthin, might be useful for preventing or treating this condition. Lutein and zeaxanthin, in particular, accumulate in the retina, the tissue in the eye that is damaged by AMD.
For U.S. food and dietary supplement labeling purposes the amount in a serving is expressed as a percent of Daily Value (%DV). For vitamin E labeling purposes 100% of the Daily Value was 30 IU, but as of May 27, 2016 it was revised to 15 mg to bring it into agreement with the RDA.[31] A table of the old and new adult Daily Values is provided at Reference Daily Intake. The original deadline to be in compliance was July 28, 2018, but on September 29, 2017 the FDA released a proposed rule that extended the deadline to January 1, 2020 for large companies and January 1, 2021 for small companies.[32] European Union regulations require that labels declare energy, protein, fat, saturated fat, carbohydrates, sugars, and salt. Voluntary nutrients may be shown if present in significant amounts. Instead of Daily Values, amounts are shown as percent of Reference Intakes (RIs). For vitamin E, 100% RI was set at 12 mg in 2011.[33]
Vitamin E may have various roles as a vitamin.[3] Many biological functions have been postulated, including a role as a fat-soluble antioxidant.[3] In this role, vitamin E acts as a radical scavenger, delivering a hydrogen (H) atom to free radicals. At 323 kJ/mol, the O-H bond in tocopherols is about 10% weaker than in most other phenols.[14] This weak bond allows the vitamin to donate a hydrogen atom to the peroxyl radical and other free radicals, minimizing their damaging effect. The thus-generated tocopheryl radical is recycled to tocopherol by a redox reaction with a hydrogen donor, such as vitamin C.[15] As it is fat-soluble, vitamin E is incorporated into cell membranes, which are therefore protected from oxidative damage.
Baeten, J. M., McClelland, R. S., Overbaugh, J., Richardson, B. A., Emery, S., Lavreys, L., Mandaliya, K., Bankson, D. D., Ndinya-Achola, J. O., Bwayo, J. J., and Kreiss, J. K. Vitamin A supplementation and human immunodeficiency virus type 1 shedding in women: results of a randomized clinical trial. J Infect.Dis 4-15-2002;185(8):1187-1191. View abstract.

In 1747, the Scottish surgeon James Lind discovered that citrus foods helped prevent scurvy, a particularly deadly disease in which collagen is not properly formed, causing poor wound healing, bleeding of the gums, severe pain, and death.[57] In 1753, Lind published his Treatise on the Scurvy, which recommended using lemons and limes to avoid scurvy, which was adopted by the British Royal Navy. This led to the nickname limey for British sailors. Lind's discovery, however, was not widely accepted by individuals in the Royal Navy's Arctic expeditions in the 19th century, where it was widely believed that scurvy could be prevented by practicing good hygiene, regular exercise, and maintaining the morale of the crew while on board, rather than by a diet of fresh food.[57] As a result, Arctic expeditions continued to be plagued by scurvy and other deficiency diseases. In the early 20th century, when Robert Falcon Scott made his two expeditions to the Antarctic, the prevailing medical theory at the time was that scurvy was caused by "tainted" canned food.[57]
* These ULs, expressed in mcg and in IUs (where 1 mcg = 3.33 IU), only apply to products from animal sources and supplements whose vitamin A comes entirely from retinol or ester forms, such as retinyl palmitate. However, many dietary supplements (such as multivitamins) do not provide all of their vitamin A as retinol or its ester forms. For example, the vitamin A in some supplements consists partly or entirely of beta-carotene or other provitamin A carotenoids. In such cases, the percentage of retinol or retinyl ester in the supplement should be used to determine whether an individual's vitamin A intake exceeds the UL. For example, a supplement labeled as containing 10,000 IU of vitamin A with 60% from beta-carotene (and therefore 40% from retinol or retinyl ester) provides 4,000 IU of preformed vitamin A. That amount is above the UL for children from birth to 13 years but below the UL for adolescents and adults.
Fawzi, W. W., Msamanga, G. I., Spiegelman, D., Urassa, E. J., McGrath, N., Mwakagile, D., Antelman, G., Mbise, R., Herrera, G., Kapiga, S., Willett, W., and Hunter, D. J. Randomised trial of effects of vitamin supplements on pregnancy outcomes and T cell counts in HIV-1-infected women in Tanzania. Lancet 5-16-1998;351(9114):1477-1482. View abstract.
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.
Vitamins are classified as either water-soluble or fat-soluble. In humans there are 13 vitamins: 4 fat-soluble (A, D, E, and K) and 9 water-soluble (8 B vitamins and vitamin C). Water-soluble vitamins dissolve easily in water and, in general, are readily excreted from the body, to the degree that urinary output is a strong predictor of vitamin consumption.[19] Because they are not as readily stored, more consistent intake is important.[20] Fat-soluble vitamins are absorbed through the intestinal tract with the help of lipids (fats). Vitamins A and D can accumulate in the body, which can result in dangerous hypervitaminosis. Fat-soluble vitamin deficiency due to malabsorption is of particular significance in cystic fibrosis.[21]
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