Nutrition & Health – 2004
 
The Molecular Basis of Milk’s Health Value - Bruce German, UC Davis
Effects of Whey Protein on Weight Loss, Glucose and Lipid Metabolism in Obese Women with Insulin Resistance and Polycystic Ovary Syndrome* - Sidika Kasim-Karakas, UC Davis


The Molecular Basis of Milk’s Health Value

Bruce German, UC Davis

Project Objectives:
· Develop and assemble the set of software tools necessary to poll various data bases including the human genome, to build a data base of genes discovered and sorted based on their promoter sequences that define them as genes expressed during lactation in the mammary gland, and by so doing obtain the subset of the human genome that is responsible for milk.
· Establish a database management tool that provides access to the milk genome data base, annotates the data base and coordinates ongoing research using the data base all within a web site environment.
· Create software protocols that will explore the structure and regulation of those genes that are induced by lactation within mammary epithelial cells and begin to assign these genes to their metabolic activities.
· Provide a collaborative environment using a software management system that coordinates researchers at the University of California and beyond to ascribe the structure of ‘milk genes’ to their nutritional functions and nutritional value to humans as food components.

The objectives of the project were to establish milk as a genetic model for foods for health within the dairy research community as an International Consortium, within the scientific community using a series of publications and presentations and within the lay public by influencing opinion leaders and the media. We produced 22 peer reviewed journal articles and book chapters. Presentations were made at 46 National and International scientific conferences. Media, state and federal agencies including the California Secretary of Agriculture were contacted or have initiated contact. In addition, we have spun out two more substantial and long term programs, the International Milk Genomics Consortium and a UC Davis project to establish the functional annotation of milk oligosaccharides. The importance to the dairy industry has been both specific (identifying bioactive compounds) and general (establishing milk as a scientific model for further research).

The agricultural and food research communities are seeking to develop foods that provide enhanced health to each individual. Unfortunately, the means to achieve this goal are not easy. Public health is largely based on reversing existing disease or preventing diseases of essential nutrient deficiencies. Scientists have not reached agreement as to what physiological targets would be used to discover foods that improve the health of already healthy individuals. Fortunately, there is a biological model that can be used to achieve such a goal—mammalian milk. Milk provides myriad examples of food ingredients, designed by selective Darwinian evolutionary pressure, to provide benefits to health and that improve the competitive success of offspring. Milk uses highly creative strategies to promote health, such as stimulating beneficial microflora, enhancing the absorption of nutrients, protecting the consumer by binding and eliminating toxins and pathogens, and educating the immune system to the presence of potential pathogens. The new tools of bio-technology make it possible to take different approaches to studying the components of milk, not only the ingested proteins and their structures, their catalytic activities and products as proteins, oligosaccharides and lipids, but determining how they are regulated, what their evolutionary history is and how they perform their specific functions. Analyses of mammalian genomes are illuminating the genes responsible for milk and how they vary in sequence and expression with species, lactation, time and physiological state. The knowledge emerging about milk's structures, functions and benefits is guiding scientists to new targets of food ingredients, new benefits from consuming specific foods and how to assemble delicious foods that deliver safety, quality, convenience, delight and improved health.

Publications
1. Watkins, S. M. Hammock, B.D. Newman, J. W. & German J. B. Individual metabolism should guide agriculture toward foods for improved health and nutrition. Am. J. of Clinical Nutrition, Vol. 74, No. 3, 283-286, Sept. 2001

2. Medina I, Tombo I, Satue-Gracia MT, German JB, Frankel EN. Effects of natural phenolics on the antioxidant activity of lactoferrin in liposomes and oil-in-water emulsions. J Agric Food Chem 2002 Apr 10;50(8):2392-9

3. German JB, M. Roberts, L. Fay, and S. Watkins Metabolomics and Individual Metabolic Assessment: The Next Great Challenge for Nutrition J. Nutrition September 2002 132(9): 2486-7

4. German JB, Dillard CJ. & Ward RF, Bioactives in milk. Cur. Opn in Clin. Nutr. &Metabolic Care 2002 Nov;5(6):653-8.

5. Watkins SM, German JB. Toward the implementation of metabolic assessment of human health and nutrition Curr Opin Biotechnology 2002 October;13(5):512-16

6. Ward RE and German JB Zoonutrients and Health Food Technology March 2003, Volume 56, No.3: 30-36

7. German, J. Bruce Matthew Alan Roberts and Steven M. Watkins Genomics and Metabolomics as Markers for the Interaction of Diet and Health: Lessons from Lipids J. Nutrition 2003 Jun;133(6 Suppl 1):2078S-2083S

8. Astaire JC, Ward R, German JB, Jimenez-Flores R. Concentration of polar MFGM lipids from buttermilk by microfiltration and supercritical fluid extraction. J Dairy Sci. 2003 Jul;86(7):2297-307.

9. German, J. Bruce Matthew Alan Roberts and Steven M. Watkins Personal Metabolomics as a next generation Nutritional Assessment J Nutr. 2003 Dec;133(12):4260-6

10. German JB, Dillard CJ. and Ward RF, Milk: A model for nutrition in the 21st century. Australian Journal of Dairy Technology 2003 August Volume 58 2 72-77.

11. German JB, Implications of Genomics for Food and Health Australian Jour. of Dairy Technology 2003 August Volume 58 2 38-44.

12. Turini ME, Boza JJ, Gueissaz N, Moennoz D, Montigon F, Vuichoud J, Gremaud G, Pouteau E, Piguet C, Perrin I, Verguet C, Finot PA, German B. Short-term dietary conjugated linoleic acid supplementation does not enhance the recovery of immunodepleted dexamethasone-treated rats Eur J Nutr. 2003 Jun;42(3):171-9

13. German J.B. and Watzke H.J. 2004. Personalizing foods for health and delight. Comprehensive Reviews in Food Science and Food Safety 3(4): 145–151

14. German J.B. Roberts M.A. and Watkins S.M. Personal Metabolomics as a Next Generation Nutritional Assessment. J. Nutr. 133: 2003

15. Neeser J-R and German JB, editors (2004) Bioprocess and Biotechnology for Functional Foods and Nutraceuticals. Marcel Dekker, New York, NY

16. Ward RE, German JB. Understanding Milk's Bioactive Components: A Goal for the Genomics Toolbox J Nutr. 2004 Apr;134(4):962S-7S

17. Ward R.E., Watzke H.J., Jiménez-Flores R. and German J.B. (2004). Bioguided processing: A paradigm change in food production. Food Technology 58(5): 44–48

18. German J.B. Dillard C.J. Saturated fats: What dietary intake? American Journal of Clinical Nutrition. 80, 550-560 2004

19. German J.B., Bauman D.E., Burrin D.G., Failla M.L., Freake H.C., King J.C., Klein S., Milner J.A., Pelto G.H. Rasmussen K.M. and Zeisel. S.H. 2004. Metabolomics in the opening decade of the 21st century: Building the roads to individualized health. The Journal of Nutrition 134: 2729–2732

20. German J.B., Yeretzian C. & Watzke H.J. Personalizing Foods for Health and Preference. Food Technology 58:12, 26-31, 2004

21. German J.B. and Watkins S.M. (2004) Metabolic assessment–a key to nutritional strategies for health. Trends in food Science & Technology 15: 541–549

22. German B., Young VR. Nutrition and genomics. Nestle Nutr Workshop Ser Clin Perform Programme. 2004;(9):243-61; discussion 261-3.

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Effects of Whey Protein on Weight Loss, Glucose and Lipid Metabolism in Obese Women with Insulin Resistance and Polycystic Ovary Syndrome*

Sidika Kasim-Karakas, UC Davis

Project Objectives
Our objective is to investigate whether a whey protein enriched high-protein diet that delivers 30% of the energy from protein achieves larger amounts of weight loss, maintains the lean body-mass, and improves glucose and lipid metabolism more than a diet containing 15%-protein.

Progress
So far, we completed the clinical studies in the first cohort of patients and carrying out the laboratory measurements.  We are also recruiting the second cohort.

Although it is too premature to reach any firm conclusions, our studies to date indicate novel mechanisms by which whey protein may be beneficial during weight loss.  It appears that while carbohydrate ingestion leads to wide fluctuations in blood glucose levels, and causes secretion of cortisol and adrenal male hormones, whey ingestion maintains steady blood glucose levels and avoids secretion of these hormones.  Since cortisol plays a role in the development of abdominal obesity and insulin resistance, and adrenal male hormones increase facial and body hair in women; it is likely that long-term effects of whey supplementation will be more favorable than those of the carbohydrates. 

The significance and industry benefit from this work
In the last decades low-fat, high carbohydrate diets were promoted to prevent obesity and achieve weight loss.  During this time, both obesity and diabetes reached epidemic proportions.  Our findings may explain the reasons for the failure of high-carbohydrate diets, and offer the mechanistic reasons to support the use of high-protein diets. Since these results are being obtained using whey protein, the whey industry should benefit from publicizing these favorable findings.

Conclusions
Potentially, partial replacement of carbohydrates with whey protein may help to prevent obesity, insulin resistance and possibly type 2 diabetes, in the long term.

* indicates continuing project

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2009 CDRF - Research photos courtesy of USDA Agriculture Research Service.