Monosodium Glutamate & Obesity

1. Monosodium Glutamate & Obesity Julia Humphrey Central Washington University

2. Objectives • Understand the difference between natural and manufactured glutamate • Acknowledge the potential relationship between MSG & appetite • Learn the effects of MSG during pregnancy & in offspring • Know how much MSG is consumed & where it is hidden

3. What is Monosodium Glutamate (MSG) • Favor enhancer/food additive largely used in the food industry • Responsible for umami/savory taste • When detected by taste buds, it signals the protein presence in the diet • Thought to mainly be in Asian cuisine • Hidden in many processed foods • Used in place of sodium

4. Natural vs. Processed Glutamate • MSG is the manufactured salt of glutamic acid • Glutamate is the sodium salt of glutamic acid • Key to the savory umami taste • Glutamate in nature • L-glutamic acid • Exists as part of proteins • Broken down as a part of protein digestion • Natural constituent to fermented foods • MSG • D-glutamic acid • Refined, can be readily absorbed into circulation • Not bound to proteins, levels spike upon consumption • Possibility of “toxicity” = MSG sensitivity

5. MSG & Obesity History • 1960s Debons et al. • Systemically administered MSG in mice found a pattern of obesity & hypothalamic damage • This lead to MSG admin. as the most widely used model to induce obesity in rats • Induces a lesion of arcuate nucleus in hypothalamus

6. MSG & Obesity • Experimental studies in rats • The arcuatenucleus proposed as an important site of leptin action • Leptinproduced by adipose cells • Essential in maintenance of appetite, energy homeostasis, & body weight • MSG administered subcutaneously in newborns • Lesion of the hypothalamic nucleus • Leptin action reduced likely as a result of lack of leptin receptors in arcuate nucleus

7. Obesity, voracity, and short stature: the impact of glutamate on the regulation of appetiteHermanussen et al. 2006 • Purpose • Effects of oral administration of MSG in pregnant rats and offspring • Subjects/Methods • 32 pregnant rats, day 14 of pregnancy divided into 4 groups • Group 1 (n=8): no extra MSG • Group 2 (n=8): 2.5 g MSG per day • Group 3 (n=8): 5.0 g MSG per day • Group 4 (n=8): no extra MSG during pregnancy offspring injected with 4mg/g MSG • Offspring killed half at day 30 and rest at day 90

8. Obesity, voracity, and short stature: the impact of glutamate on the regulation of appetiteHermanussen et al. 2006 Appetite • Results • Maternal feeding with 5 g/d resulted in severe birth weight reduction (p < 0.01) • Leptin levels reduced in MSG-fed groups (p < 0.05) • MSG-fed animals contained more body fat at day 30 and 90 than controls (p < 0.05) • Impaired glucose tolerance • Insulin resistance • 2.5 and 5 g/day MSG consumption showed marked voracity

9. Monosodium glutamate versus diet induced obesity in pregnant rats and their offspringAfifi and Abbas 2011 • Purpose • Compare oral administration of large doses of MSG with high calorie diet in pregnant rats & offspring • Subjects/Methods • 90 female rats randomly divided into 3 groups • Group 1 (n=30): normal chow 4.5% fat • Group 2 (n=30): normal chow + 100 g/kg MSG • Group 3 (n=30): high fat chow 31% fat

10. Monosodium glutamate versus diet induced obesity in pregnant rats and their offspringAfifi and Abbas 2011 • Subjects/Methods • Female rats allowed to mate and further divided into groups • C10 (n=10): control preg sacrificed on 10th day • MSG10 (n=10): MSG treated preg sacrificed on 10th day • HC10 (n=10): high calorie preg sacrificed 10th day • C20 (n=10): control preg sacrificed on 20th day • MSG20 (n=10): MSG treated preg sacrificed 20th day • HC20 (n=10): high calorie preg sacrificed 20th day • Offspring of female rats • CO (n=10): control preg offspring sacrificed 10th day • MSGO (n=10): MSG preg offspring sacrificed 10th day • HC (n=10): high calorie preg offspring sacrificed 10th day

11. Monosodium glutamate versus diet induced obesity in pregnant rats and their offspringAfifi and Abbas 2011

12. MSG Consumption • FDA • Considers MSG as a food additive “generally recognized as safe” • Not required to list amount of MSG in Nutrition Facts panel • Large variation in MSG consumption • UK (1991): 580 mg/d general 4.68 g/d in extreme users • China (2010): 3.8 g/d • Thailand (2012): 4.0 g/d • Japan & Korea (1990’s): 1.2-1.7 g/d • Speculated intake is up to 10 g/d

13. Consumption of MSG in relation to incidence of overweight in chinese adults: China Health and Nutrition SurveyHe et al. 2011 • Subjects • Longitudinal open-cohort, ongoing, nationwide survey 1991-2006 • 10,095 Chinese men and women 18-65 yr • Methods • MSG consumption dietary data both in the household & individual • All food purchases, home production, and processed snack foods were weighed and recorded • 24-hour recall for 3 consecutive days • MSG intake for each household member estimated based on the proportion of each individual’s food consumption • MSG intake separated into quintiles • Chi square test

14. Consumption of MSG in relation to incidence of overweight in chinese adults: China Health and Nutrition SurveyHe et al. 2011 • Results • Mean cumulative MSG intake 1.8 g/d • MSG positively associated with BMI in dose-response manner (p < 0.01) • Highest MSG quintile 33% more likely to be overweight • Higher BMI, income, lower physical activity • Pilot Study • Examine association between MSG and serum leptin • MSG intake positively related to serum leptin concentrations • Serum leptin concentration increased by 0.45 ng/mL with every 1-g increase in MSG intake

15. Limitations to Studies • Majority on pregnancy & neonatal outcome is in rodents • Not ethical to perform on humans • MSG dose is very large compared to actual consumption in humans

16. Is MSG Safe During Pregnancy? • Animal studies • Result of maternal MSG consumption • Low birth weight in offspring • Increased insulin resistance in offspring • Leptinlevels reduced in offspring • Leptin resistance in pregnant rat • Increased abdominal fat in pregnant rat • Placental barrier • Controls the passage of glutamate from maternal plasma to fetus, metabolizing it before it reaches the fetal circulation • MSG-sensitivity • Headaches, nausea, numbness, weakness when consuming MSG containing foods • Want to consume fresh unprocessed as much as possible during pregnancy • Consult doctor

17. “Hidden” MSG • Not labeled as MSG • Hydrolyzed (anything), glutamate, glutamic acid, yeast extract, soy sauce, soy protein, gelatin, flavors, flavoring, bouillon, broth, seasonings, etc • Found in common food items • Processed cheese, salad dressings, meat & vegetable stocks/broth, soups, vegetable dips, condiments, chips, pasta sauce • Fast food: KFC • Increase in MSG production • Increase in processed foods = increased consumption • 200 tons per year in 1969 • 800 tons per year in 2001 • Possible that exposure in utero could be a contributing factor to increasing obesity rates

18. Conclusion • Obesity is a multifactorial disease • Related to diet, physical activity, genetics, environment • Like sugar and fat consumption MSG may simply be one factor in the mix • Would like to see national study in U.S • Difficult since NHANES does not provide MSG info

19. Resources • Afifi MM, Abbas AM. Monosodium glutamate versus diet induced obesity in pregnant rats and their offspring. ActaPhysiologicaHungarica2011;98;2:177-188 • Collison K, Makhoul N, Zaidi M, Inglis A, Andres B, Ubungen R, Shoukri M, Al-Mohanna A. Interactive effects of neonatal exposure to monosodium glutamate and aspartame on glucose homeostasis. Nutrition & Metabolism 2012;5;58:1-13 • Diemen V, Trindade M. Effect of the oral administration of monosodium glutamate during pregnancy and breast-feeding in the offspring of pregnant Wistar rats. ActaCirurgicaBrasileria2010;25;1:37-42 • FriedlerB, Grimm V. Prenatal monosodium glutamate (MSG) treatment given through the mother’s diet causes behavioral deficits in rat offspring. International Journal of Neuroscience 1984;23:117-126 • He K, Du S, Xun P, Sharma S, Wang H, Zhai F, Popkin B. Consumption of monosodium glutamate in relation to incidence of overweight in Chinese adults: China Health and Nutrition Survey (CHNS). American Journal of Clinical Nutrition 2011;93:1328-36 • Hermanussen M, Garcia AP, Voigt M, Salazar V, Tresguerres JAF. Obesity, voracity, and short stature: the impact of glutamate on the regulation of appetite. European Journal of Clinical Nutrition 2006;60:25-31 • Insawang T, Selmi C, Cha’on U, Pethlert S, Yongvanit P, Areejitanusorn P, Boonsiri P, Khampitak T, Tangrassmeeprasert R, Pinitsoontorn C, Prasongwattana V, Gershwin M, Hammock B. Monosodium glutamate (MSG) intake is associated with the prevalence of metabolic syndrome in a rural Thai population. Nutrition & Metabolism 2012;9;50:1-6 • Yu T, Zhao Y, Shi W, Ma R, Yu L. Effects of maternal oral administration of monosodium glutamate at a late stage of pregnancy on developing mouse fetal brain. Brain Research 1997:195-206 • MSG Truth website http://www.msgtruth.org/avoid.htm. Accessed July 12, 2013 • Names of ingredients that contain processed free glutamic acid (MSG) http://www.truthinlabeling.org/hiddensources.html . Accessed July 12, 2013 • Glutamic Acid - It Is Not MSG or Monosodium Glutamate http://www.edenfoods.com/articles/view.php?articles_id=207. Accessed July 12, 2013

20. What are your thoughts? Questions?