Vitamin A is a fat-soluble vitamin that mediates normal functioning of the mucus membranes of the eye and respiratory tract, and the formation of visual pigments in the eye. It is also essential for normal tissue growth and differentiation. Vitamin A can be manufactured in the body from beta-carotene, found in a variety of foods, particularly green vegetables and carrots as well as being obtained as retinol from fish oils, meat, and milk. Vitamin A deficiency increases the risk of infection, especially of the respiratory, digestive, and urinogenital tracts, and causes a number eye disorders, including night blindness. Excessive intakes of vitamin A can lead to nausea, vomiting, anorexia, headaches, hairlessness, bone and joint pain, and bone fragility.

Investigators at the Sloan-Kettering Institute for Cancer Research (New York, NY, USA) sought to determine why both a deficiency and an excess of vitamin A caused damage to so many different organs of the body. To this end they worked with cell cultures from humans and mice that expressed mutations to various molecular pathways governing functioning of the mitochondria.

They reported in the October 7, 2009, online edition of the FASEB Journal that retinol was essential for the metabolic fitness of mitochondria. When cells were deprived of retinol, respiration and ATP synthesis declined to basal levels. Energy output recovered to significantly higher levels as soon as retinol was restored to physiological concentration, without the need for metabolic conversion to other retinoids. At the molecular level retinol was found to be an essential cofactor of the enzyme protein kinase C-delta (PKC-delta), without which this enzyme failed to be activated in mitochondria. The molecular complex of PKC-delta and retinol increased energy output by signaling the pyruvate dehydrogenase complex for enhanced flux of pyruvate into the Krebs cycle.

"Our work illuminates the value and potential harm of vitamin A use in cosmetic creams and nutritional supplements," said senior author Dr. Ulrich Hammerling, professor of immunology at the Sloan-Kettering Institute for Cancer Research. "Although vitamin A deficiency is not very common in our society, over-use of this vitamin could cause significant dysregulation of energy production impacting cell growth and cell death."

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Sloan-Kettering Institute for Cancer Research