This paper assesses critically the science base that underpins the argument that oxidative damage is a significant causative factor in the development of human diseases and that antioxidants are capable of preventing or ameliorating these disease processes. The assessment has been carried out under a number of headings, and some recommendations for future research are made based on the present day knowledge base. The knowledge database (1) Consideration of the basic science that underlies understanding of the role of free radicals in causing cellular pathologies, and the role of antioxidants in preventing this, shows that an imbalance of reactive oxygen species and antioxidant defence systems may lead to chemical modifications of biologically relevant macromolecules. This imbalance provides a logical pathobiochemical mechanism for the initiation and development of several disease states. Experimental data obtained in vivo provide evidence that antioxidants function in systems that scavenge reactive oxygen species and that these are relevant to what occurs in vivo. The relevance in vivo of these observations depends inter alia on knowledge of the uptake and distribution of the antioxidant within the human body, and on what tissue levels of the antioxidant may be expected in relation to dietary levels. (2) There is some way to go until validated precise methods are available for measuring biomarkers of oxidative damage in human subjects in vivo under minimally invasive conditions. With respect to oxidative damage in DNa, HPLC and GC-mass spectrophotometry methods have both merits and limitations. Lipid oxidation products in plasma are best measured as isoprostanes or as lipid hydroperoxides using specific HPLC techniques. Development of isoprostane measurement will advance specificity and precision. The measurement of oxidative damage to proteins has some potential but such methods have not been effectively exploited. (3) Epidemiological studies support the hypothesis that the major antioxidant nutrients vitamin E and vitamin C, and beta-carotene (which may or may not be acting as an antioxidant in vivo), may play a beneficial role in prevention of several chronic disorders. More research is needed on the impact of other non-nutrient compounds, such as other carotenoids and flavonoids, on human health. In general, human intervention studies using hard end-points are the gold standard. Trials are restricted mainly to the major antioxidants and do not allow firm conclusions because of inconsistent findings, an insufficient number of studies and the use of varying doses. There is evidence that large doses of beta-carotene may be deleterious to the health of certain subgroups of the population such as heavy habitual smokers. (4) With respect to the safety of administration of supplementary vitamins, vitamin C is safe at levels of supplementation up to 600 mg/d, and higher levels, up to 2000 mg/d, are without risk. Vitamin E has a very low human toxicity and an intake of 1000 mg/d is without risk; 3200 mg/d has been shown to be without any consistent risk. Large intakes of beta-carotene must be viewed with caution because they have been shown to confer detriment to a population at high risk of lung cancer when administered after many years of high risk (smoking) behaviour. Until further work clarifies the situation in heavy smokers with respect to taking supplements, larger doses should be avoided by such individuals. There is little reliable information about the human toxicology of flavonoids and related non-nutrient antioxidant constituents of the diet. (5) The food industry has long experience in the control of oxidative damage in foods and this experience can be used to advantage for the protection of food antioxidants which are beneficial. Some of these, such as vitamins C and E and beta-carotene, are well known, and strategies for their protection in foods are already exploited by food technologies. (ABSTRACT TRUNCATED)

/pdf/functional-food-science-and-defence-against-reactive-84rpfoebh4.pdf

Functional food science and defence against reactive oxidative species.

Antioxidant potentials of vitamin A and carotenoids and their relevance to heart disease.

ContextIngestion of toxic amounts of vitamin A affects bone remodeling and
can have adverse skeletal effects in animals. The possibility has been raised
that long-term high vitamin A intake could contribute to fracture risk in
humans.ObjectiveTo assess the relationship between high vitamin A intake from foods
and supplements and risk of hip fracture among postmenopausal women.DesignProspective analysis begun in 1980 with 18 years of follow-up within
the Nurses' Health Study.SettingGeneral community of registered nurses within 11 US states.ParticipantsA total of 72 337 postmenopausal women aged 34 to 77 years.Main Outcome MeasuresIncident hip fractures resulting from low or moderate trauma, analyzed
by quintiles of vitamin A intake and by use of multivitamins and vitamin A
supplements, assessed at baseline and updated during follow-up.ResultsFrom 1980 to 1998, 603 incident hip fractures resulting from low or
moderate trauma were identified. After controlling for confounding factors,
women in the highest quintile of total vitamin A intake (≥3000 µg/d
of retinol equivalents [RE]) had a significantly elevated relative risk (RR)
of hip fracture (RR, 1.48; 95% confidence interval [CI], 1.05-2.07; P for trend = .003) compared with women in the lowest quintile
of intake (<1250 µg/d of RE). This increased risk was attributable
primarily to retinol (RR, 1.89; 95% CI, 1.33-2.68; P
for trend <.001 comparing ≥2000 µg/d vs <500 µg/d). The
association of high retinol intake with hip fracture was attenuated among
women using postmenopausal estrogens. Beta carotene did not contribute significantly
to fracture risk (RR, 1.22; 95% CI, 0.90-1.66; P
for trend = .10 comparing ≥6300 µg/d vs <2550 µg/d). Women
currently taking a specific vitamin A supplement had a nonsignificant 40%
increased risk of hip fracture (RR, 1.40; 95% CI, 0.99-1.99) compared with
those not taking that supplement, and, among women not taking supplemental
vitamin A, retinol from food was significantly associated with fracture risk
(RR, 1.69; 95% CI, 1.05-2.74; P for trend = .05 comparing ≥1000
µg/d vs <400 µg/d).ConclusionsLong-term intake of a diet high in retinol may promote the development
of osteoporotic hip fractures in women. The amounts of retinol in fortified
foods and vitamin supplements may need to be reassessed.

https://jamanetwork.com/journals/jama/articlepdf/194525/JOC11339.pdf

Vitamin A intake and hip fractures among postmenopausal women.

S-Adenosylmethionine Jose M. Mato and Shelly C. Lu Aloe Vera Santiago Rodriguez, Steven Dentali, and Devon Powell Androstenedione Benjamin Z. Leder L-Arginine Mauro Maccario, Guglielmo Beccuti, Valentina Gasco, Mariangela Seardo, Gianluca Aimaretti, Emanuela Arvat, Fabio Lanfranco, and Ezio Ghigo Astragalus Roy Upton Bilberry Marilyn Barrett Biotin Donald M. Mock Bitter Orange Steffany Haaz, K. Y. Williams, Kevin R. Fontaine, and David B. Allison Black Cohosh Daniel S. Fabricant, Elizabeth C. Krause, and Norman R. Farnsworth Blue-Green Algae (Cyanobacteria) WayneW. Carmichael and Mary Stukenberg with Joseph M. Betz Boron Curtiss Hunt Caffeine Harris R. Lieberman, Christina E. Carvey, and Lauren A. Thompson Calcium Robert P. Heaney Propionyl-L-Carnitine Charles J. Rebouche ss-Carotene Elizabeth J. Johnson and Robert M. Russell Carotenoids Overview Elizabeth J. Johnson and Robert M. Russell Cascara Sagrada Kapil K. Soni and Gail B. Mahady Chaste Tree Gail B. Mahady, Joanna L. Michel, and Kapil K. Soni Choline Steven H. Zeisel Chondroitin Sulfate Karla L. Miller and Daniel O. Clegg Chromium Richard A. Anderson andWilliam T. Cefalu Coenzyme Q10 Gustav Dallner and Roland Stocker Conjugated Linoleic Acid Kristina B. Martinez, Arion J. Kennedy, and Michael K. McIntosh Copper Leslie M. Klevay Cordyceps John Holliday, Matt Cleaver, Mojca Tajnik, Joseph M. Cerecedes, and Solomon P. Wasser Cranberry Marguerite A. Klein Creatine G. S. Salomons, C. Jakobs, and M. Wyss Dong Quai Roy Upton Dehydroepiandrosterone Salvatore Alesci, Irini Manoli, and Marc R. Blackman Rudolf Bauer and Karin Woelkart Elderberry Madeleine Mumcuoglu, Daniel Safirman, and Mina Ferne Eleuthero Josef A. Brinckmann Ephedra Anne L. Thurn with Joseph M. Betz Evening Primrose Fereidoon Shahidi and Homan Miraliakbari Feverfew Dennis V. C. Awang Flaxseed Lilian U. Thompson and Julie K. Mason Folate Pamela Bagley and Barry Shane French Maritime Pine Peter J. Rohdewald Garcinia Frank Greenway Garlic J. A. Milner Ginger Tieraona Low Dog Ginkgo Kristian Stromgaard, Stine B. Vogensen, Joseph Steet, and Koji Nakanishi Ginseng, American Chong-Zhi Wang and Chun-Su Yuan Ginseng, Asian Lee Jia and Fabio Soldati Glucosamine Karla L. Miller and Daniel O. Clegg Glutamine Steven F. Abcouwer Goldenseal Dennis J. McKenna and Gregory A. Plotnikoff Grape Seed Extract Dallas L. Clouatre, Chithan Kandaswami, and Kevin M. Connolly Green Tea Polyphenols Shengmin Sang, Joshua D. Lambert, Chi-Tang Ho, and Chung S. Yang Hawthorn Egon Koch, Werner R. Busse,Wiltrud Juretzek, and Vitali Chevts 5-Hydroxytryptophan Pedro Del Corral, Kathryn S. King, and Karel Pacak Iron Laura E. Murray-Kolb and John Beard Isoflavones Mark Messina Isothiocyanates Elizabeth H. Jeffery and Anna-Sigrid Keck Kava Michael J. Balick, Katherine Herrera, and Steven M. Musser Lactobacilli and Bifidobacteria Linda C. Duffy, Stephen Sporn, Patricia Hibberd, Carol Pontzer, Gloria Solano-Aguilar, Susan V. Lynch, and Crystal McDade-Ngutter Licorice Decio Armanini, Cristina Fiore, Jens Bielenberg, and Eugenio Ragazzi alpha-Lipoic Acid/Thioctic Acid Donald B. McCormick Lutein John Paul SanGiovanni, Emily Y. Chew, and Elizabeth J. Johnson Lycopene Rachel Kopec, Steven J. Schwartz, and Craig Hadley Maca Ilias Muhammad, Jianping Zhao, and Ikhlas A. Khan Magnesium Robert K. Rude Melatonin Amnon Brzezinski and Richard J. Wurtman Milk Thistle Elena Ladas, David J. Kroll, and Kara M. Kelly Niacin Christelle Bourgeois and Joel Moss Noni Alison D. Pawlus, Bao-Ning Su, Ye Deng, and A. Douglas Kinghorn Omega-3 Fatty Acids William S. Harris Omega-6 Fatty Acids William L. Smith and Bill Lands Pancreatic Enzymes Naresh Sundaresan, Unwanaobong Nseyo, and Joel Moss Pantothenic Acid Lawrence Sweetman Pau d'Arco Memory P. F. Elvin-Lewis and Walter H. Lewis Phosphorus John J. B. Anderson and Sanford C. Garner Polyphenols Overview Navindra P. Seeram Proanthocyanidins Catherine Kwik-Uribe, Rebecca Robbins, and Gary Beecher Pygeum Franc,ois G. Brackman and Alan Edgar with Paul M. Coates Quercetin Jae B. Park Red Clover Elizabeth C. Krause, Nancy L. Booth, Colleen E. Piersen, and Norman R. Farnsworth Reishi Solomon P. Wasser Riboflavin Richard S. Rivlin Saw Palmetto Edward M. Croom and Michael Chan Selenium Roger A. Sunde Shiitake Solomon P. Wasser St. John's Wort Jerry M. Cott Taurine Robin J. Marles, Valerie A. Assinewe, Julia A. Fogg, Milosz Kaczmarek, and Michael C. W. Sek Thiamin Hamid M. Said Turmeric Janet L. Funk Valerian Dennis V. C. Awang Vitamin A A. Catharine Ross Vitamin B6 James E. Leklem Vitamin B12 Lindsay H. Allen Vitamin C Sebastian Padayatty, Michael Graham Espey, and Mark Levine Vitamin D Patsy Brannon, Mary Frances Picciano, and Michelle K. McGuire Vitamin E Maret G. Traber Vitamin K J. W. Suttie Yohimbe Joseph M. Betz Zinc Carolyn S. Chung and Janet C. King Index

Encyclopedia of dietary supplements.

Either an excess or a deficiency of vitamin A and related compounds (retinoids) causes abnormal morphological development (teratogenesis). Potential retinoid sources come from dietary intake, nutritional supplements, and some therapeutic drugs. Therefore, understanding the mechanisms of retinoid teratogenesis is important. This review first gives an overview of the principles of teratology as they apply to retinoid-induced malformations. It then describes relevant aspects of the biochemical pathway and signal transduction of retinoids. The teratogenic activity of various retinoid compounds, the role of the retinoid receptors, and important toxicokinetic parameters in teratogenesis are reviewed.

A.K. Palmer

Papers

The toxicity of beta-carotene