The Role of the Mineral Phosphorus (P) in the Fight against Obesity and the Metabolic Syndrome Nov. 2016 - Dubai, UAE. M AYA BASSI L, P H D NUTRI TIO N P RO GRAM LEBANESE AM ERI CAN UNI VERSITY
The Obesity Epidemic WHO, 2015
The Obesity Epidemic Arab World Rahim, Hanan F. Abdul, et al. "Non-communicable diseases in the Arab world." The Lancet 383.9914 (2014): 356-367.
Obesity Burden Arab World Rahim, Hanan F. Abdul, et al. "Non-communicable diseases in the Arab world." The Lancet 383.9914 (2014): 356-367.
Obesity: an energy Imbalance
The Role of Phosphorus in Energy Balance Transition to Western Diet : high fat, high sugar but low in Phosphorus VS. Current P intake: 1.4g/d 1 0.56 mg P/Kcal Whole, unprocessed foods diet: 2.5 g/d 1mg P/Kcal Note: > RDA (700 mg/d) 2 but low per Kcal of intake UL = 4 g/d 1. Ervin RB, Wang CY, Wright JD, Kennedy-Stephenson J. Dietary intake of selected minerals for the United States population: 1999 2000. Adv Data 2004; 27: 1 5. 2. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Calcium, Magnesium, Phosphorus, Vitamin D, and Fluoride. National Academy Press: Washington, DC, 1997.
Foods Phosphorus Foods Phosphorus (High P Content) (mg per 100 grams) (Low P Content) (mg per 100 grams) Bran wheat 1200 Butter Traces Dried skimmed milk 950 Vegetable oil Traces Walnuts 510 Margarine 20 Brazil nuts 590 White sugar Traces Soya, low fat 640 Ketchup, tomato sauce 20 Cocoa powder 660 Table salt 8 Roe, cod, fried 500 Cream, 35% fat 0 Canned sardines 430 Fried spring rolls Traces Boiled crab 350 Noodles Traces Boiled lobster 280 Corn flour 30 Canned salmon 240 Boiled spaghetti 40 Raw oysters 230 Boiled pasta, macaroni 50 Fried liver 400 Boiled rice 35 Boiled lamb 320 Breakfast biscuits Traces Fillet, steak, grilled 265 Cornflakes 60 Beef burger 250 Doughnut 60 Chicken livers 350 Éclair 70 Boiled chicken 190 Trifle 90 Canned ham 280 Pizza, cheese, tomato 170 Pork chop 180 Hamburger Traces Boiled egg 230 Meat pie Traces
The Role of Phosphorus in Energy Balance Obeid, O. A. (2013). Low phosphorus status might contribute to the onset of obesity. obesity reviews, 14(8), 659-664.
The Role of Phosphorus in Energy Intake Cross over, double-blinded Healthy adults: Addition of 500 mg P/placebo to different preloads; Water, Sucrose, Fructose or Glucose 27-33% ad libitum subsequent energy Obeid OA, et al. Increased phosphorus content of preload suppresses ad libitum energy intake at subsequent meal. Int J Obes. 010;34:1446-8
The Role of Phosphorus in Energy Intake Long term (3 months) double blind, placebo controlled, trial study in obese healthy adults P supplementation with meals (375 mg, three times per day) vs. placebo Ayoub, J. J., et al. "Effect of phosphorus supplementation on weight gain and waist circumference of overweight/obese adults: a randomized clinical trial." Nutrition & diabetes 5.12 (2015): e189.
The Role of Phosphorus in Energy Intake Baseline subject characteristics Placebo Group (n=21) Phosphorous Group (n=26) P-Value Age 37 ± 3 34 ± 3 0.396 M/F 6/15 10/16 - Weight (Kg) 92.33 ± 3.27 87.73 ± 3.51 0.342 BMI (kg/m 2 ) 33.73 ± 0.84 31.40 ± 0.86 0.060 WC (cm) 109.43 ± 2.16 105.66 ± 2.36 0.245 Serum P (mg/dl) 4.11 ± 0.15 4.35 ± 0.10 0.193 Triglycerides (mg/dl) 161.50 ± 15.10 140.50 ± 15.40 0.335 Total Cholesterol (mg/dl) 221.85 ± 9.09 215.89 ± 7.94 0.624 LDL-C (mg/dl) 143.29 ± 6.81 145.71 ± 6.44 0.797 HDL-C (mg/dl) 46.30 ± 2.46 42.37 ± 2.26 0.245 Glucose (mg/dl) 95.30 ± 2.40 101.40 ± 6.20 0.357 HbA1C (%) 5.44 ± 0.09 5.63 ± 0.18 0.358 Ayoub, J. J., et al. "Effect of phosphorus supplementation on weight gain and waist circumference of overweight/obese adults: a randomized clinical trial." Nutrition & diabetes 5.12 (2015): e189.
cm Kg Kg / m2 The Role of Phosphorus in Energy Intake 2 1.13 1.5 1 0.5 0-0.5 Placebo -1-1.5 Difference in Weight * Phosphorus -0.44 2.0 1.0 0.0-1.0-2.0-3.0 0.8 0.42 0.6 0.4 0.2 0 Placebo -0.2 Phosphorus -0.4-0.16 Difference in Waist 0.38 Placebo Phosphorus Difference in BMI -4.0-3.48-5.0 Ayoub, J. J., et al. "Effect of phosphorus supplementation on weight gain and waist circumference of overweight/obese adults: a randomized clinical * * *p<0.05 vs. placebo
The Role of Phosphorus in Energy Intake Difference in Appetite Scores Ayoub, J. J., et al. "Effect of phosphorus supplementation on weight gain and waist circumference of overweight/obese adults: a randomized clinical
The Role of Phosphorus in Energy Intake: Proposed Mechanism appetite 1,2 P uptake insulin High fat High Sugar diet P Prandial P intake ATP 1.Friedman MI. Obesity and the hepatic control of feeding behavior. Drug News Perspect 2007; 20: 573 578. 2. Langhans W, Scharrer E. 1992. Metabolic control of eating. World Rev Nutr Diet 1992; 70: 1 67.
The Role of Phosphorus in Energy Expenditure Diet induced thermogenesis (DIT): increase in energy expenditure (ATP) above basal rate in response to food ingestion: 5-15% of total energy expenditure 1 Blunted DIT in Obesity and T2DM o Insulin resistance/lack of insulin: reduced uptake of substrates for ATP production We postulated that addition of P to meals improves DIT 1. Schutz, Y., et al. (1984). Diet-induced thermogenesis measured over a whole day in obese and nonobese women. The American journal of clinical nutrition, 40(3), 542-552. 2. Golay, A., etal. (1982). Glucose-induced thermogenesis in nondiabetic and diabetic obese subjects. Diabetes, 31(11), 1023-1028 3. Segal, K. R., et al. (1990a). Comparison of thermic effects of constant and relative caloric loads in lean and obese men.the American journal of clinical nutrition, 51(1), 14-21. 4. Segal, K. R., et al. (1990b). Thermic effect of a meal over 3 and 6 hours in lean and obese men. Metabolism, 39(9), 985-992.
The Role of Phosphorus in Energy Expenditure Double-blind cross over design: DIT of glucose solution was measured with or without P in lean and overweight/obese subjects Overnight Fast (10h) - Consent Form - Weight, Height - BMI - Body Composition* - VAS** - BMR*** - Glucose Solution (75 mg in in 296 ml****) - Placebo or P (500 mg) DIT DIT DIT DIT DIT - DIT - VAS t=0 t=30 t=60 t=90 t=120 t=150 t=180 - *Body composition (Bioelectrical impedance (Tanita BC-418, Tokyo, Japan)) - **Visual Analogue Scale VAS (hunger and satiety) - ***Basal Metabolic Rate BMR (Indirect calorimetry (Cosmed Fitmate, Italy)) - ****Glucose Solution (75 mg in in 296 ml (Trutol, Thermo scientific, USA)) Bassil, M., & Obeid, O. (2015). Phosphorus supplementation recovers the blunted diet induced thermogenesis in overweight and obese subjects. The FASEB Journal, 29(1 Supplement), LB372
AUC (Kcal/180 min) RMR (Kcal/min) The Role of Phosphorus in Energy Expenditure Lean 1.9 1.7 1.5 * 1.9 1.7 1.5 * Obese NS * 1.3 1.3 1.1 0.9 0.7 Glucose solution Placebo lean Phosphorus lean 1.1 0.9 0.7 Glucose solution Placebo Obese Phosphorus Obese Data are Mean ± SEM *p<0.05 vs. placebo (paired t-test) p<0.05: within-subjects comparison (Repeated Measures) RMR: Resting Metabolic Rate AUC: Area under the curve 0.5 0' 30' 60' 90' 120' 150' 180' 500000.0 400000.0 300000.0 200000.0 0.5 0' 30' 60' 90' 120' 150' 180' 500000.0 400000.0 300000.0 200000.0 * 100000.0 100000.0 0.0 0.0 Bassil, M., & Obeid, O. (2015). Phosphorus supplementation recovers the blunted diet induced thermogenesis in overweight and obese subjects. The FASEB Journal, 29(1 Supplement), LB372
The Role of Phosphorus in Energy Expenditure: Proposed Mechanism Obesity Insulin Resistance Prandial P intake P uptake & Glucose phosphorylation, driving more glucose inside cells ATP ATP Blunted Postprandial glucose uptake
The Role of Phosphorus in Metabolic Syndrome: Glucose tolerance Two cross over experiments in healthy adult lean men Experiment 1: Overnight fasted subjects randomly received: glucose (75 g) solution together with placebo or 500 mg of P tablets. Experiment 2: Overnight fasted subjects (n = 8) underwent similar procedures to those of experiment 1,except that placebo or 500 mg P tablets were given 60 min prior to glucose ingestion. Khattab, May, et al. "Phosphorus ingestion improves oral glucose tolerance of healthy male subjects: a crossover experiment." Nutrition journal 14.1 (2015): 1.
The Role of Phosphorus in Metabolic Syndrome: Glucose tolerance Experiment 1: After the ingestion of 500 mg phosphorus (- -), 75 g glucose (- -) or co-ingestion glucose + phosphorus (75 g glucose + 500 mg of phosphorus) (....). Khattab, May, et al. "Phosphorus ingestion improves oral glucose tolerance of healthy male subjects: a crossover experiment." Nutrition journal 14.1 (2015): 1.
The Role of Phosphorus in Metabolic Syndrome: Glucose tolerance Experiment 2: After the ingestion of 75 g glucose 60 min after placebo (- -) or 500 mg phosphors (....) preload. Khattab, May, et al. "Phosphorus ingestion improves oral glucose tolerance of healthy male subjects: a crossover experiment." Nutrition journal 14.1 (2015): 1.
The Role of Phosphorus in Metabolic Syndrome: Insulin Sensitivity and Blood lipids Control Diet High Fat Regular P (HF) n=30 Study duration: 12 weeks High Fat High P (HFHP) Bassil, Maya, et al. "High Phosphorus Diet Mitigates Impairments in Lipid and Glucose Metabolism Associated with Diet-Induced Obesity in Male Sprague Dawley Rats." The FASEB Journal 30.1 Supplement (2016): 291-6.
The Role of Phosphorus in Metabolic Syndrome: Insulin Sensitivity and Blood lipids Bassil, Maya, et al. "High Phosphorus Diet Mitigates Impairments in Lipid and Glucose Metabolism Associated with Diet-Induced Obesity in Male Sprague Dawley Rats." The FASEB Journal 30.1 Supplement (2016): 291-6. Diet (g/kg) Control High Fat Regular P (HF) High Fat High P (HFHP) Egg white (low P) 200 200 200 Fat (corn oil) 100 100 100 Animal fat (ghee) - 300 300 Starch 300 300 300 Sucrose 300 - - Mineral mix 35 35* 35* Vitamin mix 10 10 10 Cellulose 48.81 42.62 17.86 Potassium phosphate (KH 2 PO 4 ) 6.19 12.38 37.14 Percentage Phosphorous 0.3% 0.3% 0.9% Kcal/g 3.4 4.9 4.9
The Role of Phosphorus in Metabolic Syndrome: Insulin Sensitivity and Blood lipids Parameter Control High Fat Regular P (HF) High Fat High P (HFHP) Initial weight (g) 198.3±8.6 200.1±8.4 201.7±3.8 Total weight gain (g) 148.9±13.0 214.6±12.8* 215.1±9.1* Liver weight (g) 9.4±0.9 11.9±0.9* 12.1±0.5* Abdominal fat (g) 0.21±0.06 0.44±0.12* 0.29±0.10 Fasting Serum P (mg/dl) 7.2±2.3 7.8±2.7 7.3±2.7 Fasting Serum glucose (mg/dl) 82.7±4.0 88.4±3.4 80.4±2.6 Fasting Serum Insulin (ng/ml) 1.2±0.4 2.8±0.4* 2.2±0.5 HOMA-IR 2.9±0.9 7.1±0.9* 4.6±1.0 Bassil, Maya, et al. "High Phosphorus Diet Mitigates Impairments in Lipid and Glucose Metabolism Associated with Diet-Induced Obesity in Male Sprague Dawley Rats." The FASEB Journal 30.1 Supplement (2016): 291-6.
mg/dl U/L The Role of Phosphorus in Metabolic Syndrome: Insulin Sensitivity and Blood lipids 60.0 250.0 50.0 * * 200.0 * 40.0 150.0 30.0 Cholesterol(mg/dl) TGs(mg/dl) 100.0 ALP ALT 20.0 10.0 0.0 Control HF HFHP * p<0.05 vs. control 50.0 0.0 Control HF HFHP Bassil, Maya, et al. "High Phosphorus Diet Mitigates Impairments in Lipid and Glucose Metabolism Associated with Diet-Induced Obesity in Male Sprague Dawley Rats." The FASEB Journal 30.1 Supplement (2016): 291-6.
Summary P status is inversely associated with obesity P meal supplementation o Suppresses appetite and food intake in short term (postprandial)and long term studies (3 months) odecreases weight, BMI and waist circumference of obese adults after 3 month supplementation o Recovers the blunted induced thermogenesis in overweight and obese adults o Improves postprandial glucose tolerance and insulin sensitivity (human and animal study) omitigates hyperlipidaemia and liver toxicity associated with diet-induced obesity (animal study)
Conclusions and Recommendations Implications: promising role of meal supplementation/fortification with P in the prevention/management of obesity and metabolic syndrome o Suggested dose: 500 mg with meals 1.5 g/d + 1.4g/d (usual intake from diet) still below UL (4g/d) Future studies are warranted to explore Mechanisms of actions Long term effect on energy expenditure
Thank You! LAU Nutrition students and faculty Omar Obeid, PhD Professor American University of Beirut
References World Health Organization, 2015 Rahim, Hanan F. Abdul, et al. "Non-communicable diseases in the Arab world." The Lancet 383.9914 (2014): 356-367. Ervin RB, Wang CY, Wright JD, Kennedy-Stephenson J. Dietary intake of selected minerals for the United States population: 1999 2000. Adv Data 2004; 27: 1 5. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Calcium, Magnesium, Phosphorus, Vitamin D, and Fluoride. National Academy Press: Washington, DC, 1997. Obeid, O. A. (2013). Low phosphorus status might contribute to the onset of obesity. obesity reviews, 14(8), 659-664. Obeid OA, et al. Increased phosphorus content of preload suppresses ad libitum energy intake at subsequent meal. Int J Obes. 010;34:1446-8 Ayoub, J. J., et al. "Effect of phosphorus supplementation on weight gain and waist circumference of overweight/obese adults: a randomized clinical trial." Nutrition & diabetes 5.12 (2015): e189. Friedman MI. Obesity and the hepatic control of feeding behavior. Drug News Perspect 2007; 20: 573 578. Langhans W, Scharrer E. 1992. Metabolic control of eating. World Rev Nutr Diet 1992; 70: 1 67. Schutz, Y., et al. (1984). Diet-induced thermogenesis measured over a whole day in obese and nonobese women. The American journal of clinical nutrition, 40(3), 542-552. Golay, A., etal. (1982). Glucose-induced thermogenesis in nondiabetic and diabetic obese subjects. Diabetes, 31(11), 1023-1028 Segal, K. R., et al. (1990a). Comparison of thermic effects of constant and relative caloric loads in lean and obese men.the American journal of clinical nutrition, 51(1), 14-21. Segal, K. R., et al. (1990b). Thermic effect of a meal over 3 and 6 hours in lean and obese men. Metabolism, 39(9), 985-992. Bassil, M., & Obeid, O. (2015). Phosphorus supplementation recovers the blunted diet induced thermogenesis in overweight and obese subjects. The FASEB Journal, 29(1 Supplement), LB372