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The Effects of Whey Based and Fruit and Vegetable Based Dietary Supplements on Blood Pressure and Heart Rate Variabilit

The Effects of Whey Based and Fruit and Vegetable Based Dietary Supplements on Blood Pressure and Heart Rate Variability John Q. Zhang, MD, PhD, L.AC John Maher, DC Associate Director of Research Logan College of Chiropractic John.zhang@logan.edu March 13, 2009

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The Effects of Whey Based and Fruit and Vegetable Based Dietary Supplements on Blood Pressure and Heart Rate Variabilit

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  1. The Effects of Whey Based and Fruit and Vegetable Based Dietary Supplements on Blood Pressure and Heart Rate Variability John Q. Zhang, MD, PhD, L.AC John Maher, DC Associate Director of Research Logan College of Chiropractic John.zhang@logan.edu March 13, 2009

  2. Introduction- Zoo & Phytonutrients The purpose of this study was to determine the effect of zoonutrient (whey based) and phytonutrient (fruit and vegetable based) nutritional supplementation on the reduction of blood pressure and improving heart rate variability in pre-hypertensive and hypertensive subjects.

  3. Introduction- Definitions • Phytonutrients are generally non-essential micronutrients found in plant foods that nonetheless have a salubrious effect on human health and physiology. Examples include EGCG, resveratrol, lutein and chlorophyll. • Zoonutrients are similar except that they are sourced from animal foods. Examples include peptides, globulins, enzymes.

  4. Introduction- Diet & Supps • In a study with five hundred men and women consuming a strictly vegetarian diet for 12 days living at a hospital based health center, the authors reported a rapid reduction in blood pressure of 6% and a weight loss of 2.5 kg for men and 1 kg for women.1 • Recent studies on nutritional supplementation have also found consistent reduction of blood pressure in subjects with elevated blood pressure.2-19

  5. Introduction: Non-Rx Interventions • A recent meta-analysis of clinical nutritional and lifestyle changes evaluated the effects of numerous interventions on systolic BP . • The most effective intervention was the DASH diet followed by exercise, weight loss, sodium restriction and fish oil supplements. • The least effective were increased intake of magnesium, calcium and potassium, or reduction in alcohol intake.

  6. Introduction: Whole Food • This meta-analysis and other nutritional/diet studies emphasize the importance of the additive or synergistic effect of multiple nutrients, whole food and whole food concentrates with their nutrient combinations in a natural complex form to reduce BP and CVD.20

  7. Introduction-DairyPeptides • Studies on infants showed that di- and tri-peptides are easily absorbed in the intestine. • The antihypertensive peptides from sour milk have shown to be absorbed in the digestive system. • The functional component may include various lactic acid bacteria (Lactobacillus GG and Lactococcus lactis) that have been shown to hydrolyze milk proteins into bioactive peptides21

  8. Introduction- peptides Various studies have found that whey-derived Peptides: • may reduce blood pressure and indirectly impart coronary health. • have antioxidant activity, which improves overall cardiovascular health. • demonstrated activity in reducing dyslipidemia as well as blood pressure. • have been demonstrated efficacious in animal researches, but trials on human subjects are limited.22

  9. Introduction- Mechanism The mechanism of the bioactive whey peptides may be involved in: • ACE inhibitory activity, • opioid-like activity, • anti-thrombotic activity and • cholesterol-reducing activity.23

  10. Introduction (WZP) • To test the potential of these bioactive peptides, this study tested NanoProPRP which is a powdered drink mix made with antibiotic free, undenatured whey protein isolate (WPI) and colostrums from BovineSpongiform Encephalopathy (BSE) free herds not treated with growth hormone or hyper-immunization, or feed animal by-products. • As it is hypothesized that the zoonutrients (peptides, opiates, microflora) are the likely active ingredients as relates to hypertension, going forward we will use the designation WZP for Whey Zoonutrient Powder.

  11. Introduction- WZP • WZP* is uniquely fortified with colostrum and proline rich polypeptides (PRP), considered colostrum’s most powerful immune modulating peptides, along with organic selenium, reduced glutathione (protected in a liposome) and inulin. * The ingredients and supplemental facts can be found on the NanoProPRP canister, on BioPharma’s product literature and the company website, www.biopharmasci.com.

  12. Introduction- Fruits & Veggies • Fruits and vegetables (F&V) are a rich source of a number of essential micronutrients and phytonutrients having antioxidant properties. • Generally, fruits and vegetables in the raw state have significantly higher values as an antioxidant than the cooked state.24 • However, most Americans do not consume the recommended 7-9ervings of fruits and vegetables a day, cooked or raw. 25 • Increasingly, according to NBJ, more first world peoples take a daily fruit and/or vegetable phytonutrient supplement.

  13. Introduction- (GPP) • In this study we used Biopharma’s supplement, NanoGreens10*, a high antioxidant powdered drink mix composed of greens, fruits, vegetables, plus a few teas, herbs and spices, that incorporated a liposome delivery purported to assist bioavailability. • Going forward we will refer to this formula as GPP, green phytonutrient powder. • The ingredients and supplemental facts can be found on the NanoGreens10 canister, on BioPharma’s product literature and the company website, www.biopharmasci.com.

  14. Previous Study*- GPP • Results: “After taking the supplement for 90 days, both the systolic and diastolic blood pressure decreased significantly.” • The systolic blood pressure decreased from 140.4±17.7 mmHg to 128±14.2 mmHg, (12.4 mmHg) and • the diastolic blood pressure decreased from 90.2±7.7 mmHg to 83.1±7.4 mmHg (7.1 mmHg).20

  15. Introduction- Mechanisms The particular mechanism of the beneficial effects of taking a F&V supplement is not well established. • It has been hypothesized that phytonutrients might serve as antagonists on the aryl hydrocarbon receptor (AhR) ( an inhibitor of brady kinnin, a vasodialator),26 • provide nitrates for NO production27 • act as quenchers of reactive oxygen species (ROS) thereby favorably effecting the vascular endothelium via their antioxidant actions.28

  16. Introduction- Aims • In this study, the two specific types of supplement drink powder mixes (WZP & GPP) were tested to document their effects on cardiovascular system. • The specific aims of the study were to study the effectiveness of both of the above described zoonutrient (WZP) and phytonutrient (GPP) powdered drink mixes on blood pressure (BP) and heart rate variability (HRV), compared to a control group (CG).

  17. The Hypotheses 1) that the whey based supplement (WZP) would be effective in reducing blood pressure and increasing HRV comparing to control group (CG). 2) that the combined whey based and fruit and vegetable based supplements (WZP + GPP) would be even more effective than whey alone.

  18. Methods- # of Subjects • With an expected drop-out rate of 10 percent, this study would require approximately 57 subjects at completion.  • For the study to have sufficient power of 0.90, with a 95% confidence interval (p = 0.05), a minimum of 54 students (18 in each group) were needed to complete this study.

  19. Methods- Random Selection • Subjects were assigned into one control and two experimental groups by random numbers. • The first 60 numbers in the first two rows of the random table were used for the study. • Subjects with the lowest 20 numbers were assigned in the control group, the highest 20 in the experimental group and the middle 20 in the second experimental group. • A total of three groups of subjects were recruited in the study.

  20. Methods- Three Groups • The first group of subjects was the control group consuming 500 mg calcium per day. • The second group took 2 servings (36 gm) of WZP a day. • The third group took 2 servings each of WZP(36 gm) and GPP (24 gm) products. • All subjects were giving a three months supply of the nutritional supplement free of charge.* • The supplement was provided by Biopharma Scientific, Inc., 5375 Sorrento Pl, Solana Beach, CA 92075.

  21. Methods- Inclusion /Exclusion • Inclusion Criteria: Male or female hypertensive subjects 30-55 years old with systolic blood pressure between 130-160 mmHg, and diastolic blood pressure of 80-105 mmHg were recruited in the study. • Exclusion Criteria: Individuals with diabetes, heart, kidney, thyroid disorders, neurological diseases, and chronic disease were not recruited in the study. Female subjects who were pregnant or breast feeding were excluded. Those using drugs or medications were not permitted to participate in the study.

  22. Methods- measurements • A Biopac manual blood pressure monitor (Biopac, Santa Barbara, CA, 93117) was used in the blood pressure measurements. • All blood pressure measurements were taken twice and an average value was used in the data analysis. • Researchers taking the blood pressure measurements had training in blood pressure measurements and at least one year of experience in hypertension studies. • Body weight was taken with the six-way weight scale (Chirotron). Only the total body weight was used in the study.

  23. Methods-Measurements • Heart rate variability (HRV): Biocom’s Active ECG Scanner was used in the HRV data collection with digital signal processing software. • The Heart Scanner records an electrocardiograph (ECG) signal, computing the instantaneous changes of HRV after each recording session. The Scanner connects to the subjects through three small electrodes that attach to the left arm, right arm and left leg.

  24. Methods- HRV • A baseline HRV was recorded before treatment was given. • The HRV recording was taken in the sitting position for 5 minutes for all subjects. • No additional gels were needed for the electrodes. Special care was given to clean the skin surface to improve skin conductance.

  25. Methods- Statistics • Repeated measurements, using ANOVA analysis*, assessed the differences of nutritional supplements on blood pressure, body weight and HRV. • SigmaStat 3.5 statistical software was used for the data analysis. Significance was determined at p 0.05 • In statistics, analysis of variance (ANOVA) is a collection of statistical models, and their associated procedures, in which the observed variance is partitioned into components due to different explanatory variables.

  26. Results-Recruitment • Thirty-seven subjects (6 female) were recruited and thirty-two (5 female) completed the study. • The study initially designed to recruit 57 subjects to satisfy the power requirement to reach statistically significant difference. • It was noted in an early data analysis that the data had reached statistically significant level. • Further data collection will be based on participants’ interests in the study.

  27. Results- Three Groups • The average age of the subjects was 24.54.4 years old in the three groups. • All three groups had similar baseline characteristics in age, gender, blood pressure and HRV. • Control group (CG) has 11 subjects (3 female), WZP group had 12 subjects (2 female) and WZP + GPP had 9 subjects (0 female).

  28. Results-BP • After taking the supplement for 90 days, both the systolic and diastolic blood pressure decreased significantly in the WZP and WZP + GPP (Figure 1, 2). • No significant changes were observed in the CG (Figure 1, 2). • The systolic blood pressure decreased from 141.0±11.8 mmHg to 126.6±7.2 mmHg (P<0.05) and the diastolic blood pressure decreased from 92.8±6.2 mmHg to 84.6±9.4 mmHg (P<0.05) in the WZP. (13.4/8.2)

  29. Results-BP • The systolic blood pressure decreased from 136.3±3.1 mmHg to 125.4±5.1 mmHg (P<0.05) and the diastolic blood pressure decreased from 88.5±7.6 mmHg to 74.6±7.7 (P<0.05) mmHg in the WZP + GPP. (10.9/13.9) • In the CG group systolic blood pressure measured at 139.7±14.2 to 137.9±19.0 mmHg and the diastolic blood pressure from 89.8±6.9 to 87.0±7.7 mmHg) (P>0.05).

  30. Results-Weight & HRV • After taking the supplement for 90 days, body weight was increased significantly in CG control group from 190.9±20.9 pounds to 196.3±23.3 (P<0.05). • The body weight in the WZP and WZP + GPP group did not show significant changes (P>0.05). • The heart rate and the heart rate variability analysis did not show any significant changes.

  31. Figure 1. Systolic blood pressure changes after taking the WZP and the WZP +GPP compared to the CG ( 500 mg Ca++ pills). 180 160 140 CG Blood Pressure (mmHg) 120 WZP WZP + GPP 100 80 60 Day 0 Day 45 Day 90

  32. Figure 2. Diastolic blood pressure changes after taking the WZP and WZP +GPP compared to the CG ( 500 mg Ca++ pills). 110 90 CG Blood Pressure (mmHg) WZP WZP + GPP 70 Day 0 Day 45 Day 90 50

  33. Summary • After taking the WZP and WZP+ GPP powdered drink mix supplements for 90 days, both the systolic and diastolic blood pressures decreased significantly. • The body weight was increased in the control group but not in the two treatment groups. • HRV was not affected

  34. Discussion • The results mimic the published efficacy of the most successful dietary intervention, the Dietary Approach to Stop Hypertension + low sodium combined! (D.A.S.H II diet). (11.4/6.8.5) • The results mimic the efficacy of any one common prescription medication.(12/6) • The results mimic the efficacy of pilot studies on GPP alone 29-31

  35. JAMA Rx Study32 http://jama.ama-assn.org/cgi/content/full/288/23/2981/FIGJOC21962F2

  36. Discussion- Further Studies • However, as sample size is small, particularly in this present study, further human trials on larger and more diverse population of persons with pre-hypertension and hypertension are needed.

  37. References • McDougall J, Litzau K, Haver E, Saunders V, Spiller GA. Rapid reduction of serum cholesterol and blood pressure by a twelve-day, very low fat, strictly vegetarian diet. J Am Coll Nutr 1995 Oct;14(5):491-6 • Rouse IL, Beilin LJ, Armstrong BK, Vandongen R. Blood-pressure-lowering effect of a vegetarian diet: controlled trial in normotensive subjects. Lancet 1983;1:5-10. • Margetts BM, Beilin LJ, Vandongen R, Armstrong BK. Vegetarian diet in mild hypertension: randomized controlled trial. Br Med J 1986;293:1468-71. • Appel LJ, Moore TJ, Obarzanek E, et al. A clinical trial of the effects of dietary patterns on blood pressure. N Engl J Med 1997;336:1117-24. • Lenz TL, Monaghan MS. Lifestyle modifications for patients with hypertension. J Am Pharm Assoc (2003). 2008 Jul-Aug;48(4):e92-9. • Sharma N, Okere IC, Barrows BR, Lei B, Duda MK, Yuan CL, Previs SF, Sharov VG, Azimzadeh AM, Ernsberger P, Hoit BD, Sabbah H, Stanley WC. High-sugar diets increase cardiac dysfunction and mortality in hypertension compared to low-carbohydrate or high-starch diets. J Hypertens. 2008 Jul;26(7):1402-1410. • Sadakane A, Tsutsumi A, Gotoh T, Ishikawa S, Ojima T, Kario K, Nakamura Y, Kayaba K. Dietary patterns and levels of blood pressure and serum lipids in a Japanese population. J Epidemiol. 2008;18(2):58-67. • Reedy J, Krebs-Smith SM.A comparison of food-based recommendations and nutrient values of three food guides: USDA's MyPyramid, NHLBI's Dietary Approaches to Stop Hypertension Eating Plan, and Harvard's Healthy Eating Pyramid. J Am Diet Assoc. 2008 Mar;108(3):522-8. • Miller ER 3rd, Erlinger TP, Appel LJ. The effects of macronutrients on blood pressure and lipids: an overview of the DASH and OmniHeart trials. Curr Atheroscler Rep. 2006 Nov;8(6):460-5. • The Expert Panel. Summary of the second report of the National Cholesterol Education Program (NCEP) Expert Panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel II). JAMA 1993;269:3015- • Pelletier S, Kundrat S, Hasler CM. Effects of a functional foods nutrition education program with cardiac rehabilitation patients. J Cardiopulm Rehabil. 2003 Sep-Oct;23(5):334-40. • Whelton BP, Roccella EJ, et al. Prevalence of hypertension in the US adult population: results from the Third National Health and Nutrition Examination Survey, 1988-1991. Hypertension. 1995;25:305-313. • Beilin LJ. Non-pharmacological management of hypertension: optimal strategies for reducing cardiovascular risk. J Hypertens. 1994;12(Suppl 10):S71-S81. • Appel LJ. Nonpharmacologic therapies that reduce blood pressure: a fresh perspective. Clin Cardial. 1999;22 (suppl 7):III 1-5. • Stein PP, Black HR. The role of diet in the genesis and treatment of hypertension. Med Clin North Am. 1993;77:831-847

  38. References • Steffen LM, Jacobs DR Jr, Stevens J, Shahar E, Carithers T, Folsom AR. Associations of whole-grain, refined-grain, and fruit and vegetable consumption with risks of all-cause mortality and incident coronary artery disease and ischemic stroke: the Atherosclerosis Risk in Communities (ARIC) Study. Am J Clin Nutr. 2003 Sep;78(3):383-90. • Sauvaget C, Nagano J, Allen N, Kodama K. Vegetable and fruit intake and stroke mortality in the Hiroshima/Nagasaki Life Span Study. Stroke. 2003 Oct;34(10):2355-60. Epub 2003 Sep 18. • Hirose K, Takezaki T, Hamajima N, Miura S, Tajima K. Dietary factors protective against breast cancer in Japanese premenopausal and postmenopausal women. Int J Cancer. 2003 Nov 1;107(2):276-82. • Lee YL, Cesario T, Wang Y, Shanbrom E, Thrupp L. Antibacterial activity of vegetables and juices. Nutrition. 2003 Nov;19(11-12):994-6. • Mark C. Houston, MD, SCH, FACP, FAHA, The Role of Vascular Biology, Nutrition, and Nutraceuticals in the Prevention and Treatment of Hypertension., JANA April 2002, Supplement No. 1 p. 5 • Shortt C, O'Brien. Formation of Bioactive Peptides During Milk Fermentation, Handbook of Functional Dairy Products. CRC Press, 2003, pp 113-117 (http://books.google.com/books?id=geXneTZ13w4C) • FitzGerald RJ, Murray BA, Walsh DJ. The Emerging Role of Dairy Proteins and Bioactive Peptides in Nutrition and Health: Hypotensive Peptides from Milk Proteins. Journal of Nutrition, 0022-3166, 2004 pp 980S- 988S. • Ibid. 22, pp 985S-86S • Tarwadi K, Agte V. Potential of commonly consumed green leafy vegetables for their antioxidant capacity and its linkage with the micronutrient profile. Int J Food Sci Nutr. 2003 Nov;54(6):417-25. • Fruit and Vegetable Consumption Among Adults--- United States, 2005. Morbidity and Mortality Weekly Report, Center for Disease Control www.cdc.gov/mmwr/preview/mmwrhtml/mm5610a2.htm • Jeuken A, Keser BJ, Khan E, Brouwer A, Koeman J, Denison MS. Activation of the Ah receptor by extracts of dietary herbal supplements, vegetables, and fruits. J Agric Food Chem. 2003 Aug 27;51(18):5478-87. • Webb AJ, Patel N, Loukogeorgakis S; Okorie M; Aboud Z; Misra S; et al. Acute Blood Pressure Lowering, Vasoprotective, and Antiplatelet Properties of Dietary Nitrate via Bioconversion to Nitrite. Hypertension. 2008;51:784 • Ibid. 20, p.35 • Ibid. 20, p. 20 • Magill Mk, Gunning K, Saffel-Shrier S, Gay C. New Developments in the Management of Hypertension, American Family Physician, Vol. 68, No. 5, pp 853-864 2001 http://www.aafp.org/afp/20030901/853.html23. • Zhang J, Oxinos G, Maher J. The Effect of Fruit and Vegetable Powder Mix on Hypertensive Subjects, Journal of Chiropractic Education, Spring 2007, Vol. 21 No. 1, p 93 • Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), JAMA, Vol. 288 No. 23, December 18, 2002 http://jama.ama-assn.org/cgi/content/full/288/23/2981/FIGJOC21962F2

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