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N Maulik and G Maulik. Nutrition, epigenetic mechanisms and human disease. Boca Raton, FL: Taylor and Francis/CRC Press. 2011. 426 pp. Octavo format. Hard cover U.S. $138.95. ISBN 9781-4398-0479-7.

Those concerned with population health are increasingly realizing the importance of matching human diet and lifestyle to the genetic inheritance gained through centuries of evolution. Our constitution is such that traditional diets are likely to be tolerated better than processed food, high in salt and hydrogenated fats and low in fiber. In keeping with this view, there is growing evidence that nutritional epigenetics has a potentially important role in disease prevention, control and management. The term epigenetics, describes gene-environmental interactions; it was coined by C.H. Waddington as long ago as 1942. The present book claims to be the first to provide a comprehensive coverage of this field for the nutritionist, although I have reviewed at least one earlier monograph that covers similar territory (1). The present text comprises 14 essays by selected world experts in nutrition, epigenetic regulation and gene expression. They discuss these issues in relation to aging, cancer and various chronic diseases, exploring the interactions of nutrition with both normal and variant genotypes at the molecular level, and underlining the likely importance of epigenetics to the regulation of genetic information in both health and disease.

An early chapter focuses on aging, describing the key roles of DNA methylation, histone modification and chromatin remodeling in gene silencing. This contribution lists the many sites of epigenetic modification reported as showing associations with the

development of disease in humans. It also suggests a long list of dietary components such as garlic, green tea and resveratol that may have the potential to restore gene function through mechanisms such as histone modification and DNA methylation, The text continues with several chapters that make a careful and detailed analysis of the potential role of dietary modification in the prevention of cancer. An individual's folate status is considered in relation to DNA methylation and the risk of several malignancies. Differences between animal and human findings are noted, and the rapid genetic change seen in an actual cancer is contrasted with the slowly progressive and potentially reversible nature of the epigenetic modifications that contribute to malignancy. Potential areas of dietary influence are seen in modifying the processes of cell differentiation, inflammation, apoptosis, cell cycle control, carcinogen metabolism and angiogenesis; future advances await the ability to profile DNA methylation and histone modifications of the genome. Disturbances of histone acetylation and methylation are convincingly linked to cancers, with dietary deficiencies of biotin or the bean isoflavin genistein seen as possible causes. However, the optimal timing and dosage of any preventive treatment remains to be clarified. The administration of epigenetically active drugs and non-coding microRNAs may also have some role in the treatment of carcinomas that are too advanced to treat by more conventional means.

A variety of other areas of interest to nutritional epigeneticists are broached. It is argued that maternal over- or under-nutrition during pregnancy has a major impact on the vascular transfer of amino acids to the fetus, with lasting epigenetic effects on the growth, health, and possibly the athletic performance of the offspring. A second chapter on this

same theme suggests potential epigenetic links between poor nutrition and the development of obesity, diabetes and cancer in the offspring, pointing to evidence from long-term effects of the "Dutch Hunger Winter" (1944-45). Dietary polyphenols may find a role in countering airway inflammation and the chronic deterioration of pulmonary function that are associated with cigarette smoking, asthma and chronic obstructive pulmonary disease. A place for epigenetics is also suggested in both the prevention and the treatment of diabetes mellitus. Several histone-modifying enzymes seem linked to glycemic variability and frank diabetes, and histone deacetylases such as Sirtuin may find a role in the treatment of diabetic complications. Two final chapters consider the potential contribution of micronutrients to neural developmental disorders, neuro-behavioural disorders, and neurodegenerative diseases.

This monograph paints a broad-ranging and exciting future for the study of nutritional epigenetics. However, as individual authors underline, much still remains to be discovered, verified -and quantified, particularly at the molecular level. Many of the postulated benefits of polyphenols and flavonoids have been observed only in vitro, and little is known about ways in which their efficacy may be modified within the digestive tract. Moreover, most trials have been short-term in nature, and possible long-term adverse effects have yet to be evaluated. The tentative nature of conclusions is generally emphasized quite well, although a few chapters would be improved if they were to stress the need for critical evaluation of the available evidence.

The book seems written primarily for the experienced research investigator, even if occasional populist phrases such as "we are all looking for the magic bullet'" (p.25) are at variance with this goal. The publishers have used a small type size, and illustrations are generally simple; indeed, a coloured insert that is promised repeatedly failed to materialize on p. 80 of my copy of the book. Each chapter is supported by a listing of 100-150 references that provide a helpful introduction to recent peer-reviewed research on nutritional epigenetics. This monograph should provide interesting reading for all who wish to expand their understanding of this controversial but rapidly developing area of research.

Reference 1, Shephard, R.J. (2008). Nutrigenomics- opportunities in Asia, Edited by E.S. Tai & P.J. Gillies. S. Karger Publications, Basel, Switzerland, 2007. Book review, Appl. Physiol. Nutr, Metab. 33: 145.

Reviewed by Roy J. Shephard. Faculty of PhysicaL Education & Health, University of Toronto, Toronto, ON.

Book Review: Nutrition, Epigenetic Mechanisms, and Human Disease