Faculty Disclosure. I have nothing to disclose.

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1

2 Faculty Disclosure I have nothing to disclose.

3 Question #1 A 7-year-old boy with an enterocutaneous fistula develops an urticarial rash the day that he is started on parenteral nutrition. All of the following constituents of his parenteral nutrition could cause the rash EXCEPT: A. Intravenous fat emulsion B. Amino acid solution C. Pediatric Multivitamin solution D. Dextrose

4 Question #2: An 18-month-old vegetarian girl with presumed milk and soy protein allergy is drinking 32 ounces of enriched almond milk per day. She also eats rice, wheat, corn, fruits, and vegetables but does not consume any egg or meat products. She does not receive any vitamin or mineral supplementation. You are concerned about her intake of all of the following EXCEPT: A. Fat B. Vitamin D C. Energy D. Zinc

5 Question #3: A 6-year-old Asian boy is seen by a dietitian for follow-up nutritional assessment and education. His parents report he is allergic to milk, soy, and peanuts. He has a history of anaphylaxis while eating peanut butter a year ago. His current intake includes tofu stirfry and milk chocolate candy bars. Parents report he eats these foods at least once a week without any problems. He does not drink a milk substitute. All of the following must be done or considered at this visit EXCEPT: A. Assessment of growth and nutrient intake B. Suggesting an ageappropriate beverage C. Recommending follow-up with allergist as patient is tolerating milk and soy D. Suggesting food challenge of peanut butter at home

6 Question #4 A 6-month-old breastfed infant has significant vomiting and diarrhea within hours of being given a bottle of cow s milk formula. His mother reports that this has happened each time he has been fed the formula. She denies any skin rashes. A serum lab for IgE directed against cow s milk protein is negative. All of the following are true about this child EXCEPT: A. This consistent with IgEmediated anaphylaxis. B. This is most likely food protein-induced enterocolitis syndrome C. Cow s milk protein must be eliminated from the child s diet D. In addition to breastfeeding, a protein hydrolysate formula may be appropriate

7 Learning Objectives Improve understanding of nutrition management of children with multiple food allergies Describe the nutrition assessment of children with food allergies Understand the food and non-food issues that may impact the provision of nutrition support in children with food allergy

8 Food Allergy Concern? Increased public health concern in Western World Greater problem in children than in adults Associated with poorer nutrition outcomes

9 What s the story? Telling Food Allergies From False Alarms (The New York Times) Is Your Kid Truly Allergic? Tests Add to Food Confusion (The Wall Street Journal) Adverse Reactions to Food: Allergies & Intolerance (Digestive Diseases) Allergic Girl teaches how to eat out with allergies (CNN.com) This allergies hysteria is just nuts (British Medical Journal) Children at risk in food roulette (ChicagoTribune.com) Fear and Allergies in the Lunchroom (Newsweek) Food Allergen s Attack (Food Service Director) Food Allergies Take a Toll on Families and Finances (The New York Times)

10 Food Allergens Identified as a protein or glycoprotein Food Allergy May be more or less common depending on the society or ethnicity Resist denaturation by heat or acid

11 What is Food Allergy? Two important points: An immune response Reproducible response to food protein. Positive skin prick test or high blood test (serum specific IgE level) to the food can not diagnose food allergy without a reaction or previous exposure to food Different from a food intolerance Example: Lactose intolerance GI symptoms from milk sugar (not protein) Not an immune response Often can tolerate some milk in some forms or different amounts (such as yogurt or cheese) Other intolerances can include; reactions to preservatives (MSG), alcohol, caffeine, theobromine in chocolate.

12 Defining Food Allergy (Immunologic Reaction to Food) IgE Mediated Syndromes Mixed IgE and Non-IgE Mediated Syndromes Non-IgE Mediated Syndromes Oral allergy syndrome Eosinophilic Esophagitis Protein-induced enterocolitis Anaphylaxis Eosinophilic gastritis Protein-induced enteropathy Urticaria Eosinophilic gastroenteritis Food protein-induced enterocolitis syndrome Angioedema Atopic dermatitis Dermatitis herpetiformis, celiac diease

13 Food Allergy 15 million Americans have food allergies 3 million are school aged Between 1997 & 2007 prevalence of childhood food allergy increased by 18% 150 reported deaths each year from anaphylaxis related to food allergies in the United States 2008 National Center for Health Statistics assessment The Food Allergy & Anaphylaxis Network; Food Allergy Facts and Statistics for the U.S. 2012

14 Food Allergies in the United States Prevalence of food allergy in general population is 1-2% Nearly 3 million children have food allergies 8% of all children Young children affected most Food allergies may be resolving more slowly than previous decades Many children still allergic beyond age 5 years Some persist throughout life

15 Egg Milk Peanut Tree nut Fish Shellfish Soy Wheat Major Food Allergens

16 Table of Cross Reactive Foods Sicherer SH: J Allergy Clin Immunol, 2001

17 Evaluation of Suspected Food Reactions ALLERGY TESTING

18 How are Food Allergies Diagnosed? History of reactions at home Allergy testing must match history of reactions 50-90% of supposed food allergies are not accurate Blood tests Specific Serum IgE testing (sige) Skin tests Scratch tests

19 Diagnosis Do not test for foods a child has not been exposed to For example, do not test strawberry, beef or broccoli for a 6 month old that has never eaten these foods and is not breastfed Do not test for foods the patient tolerates

20 Test Results What do they mean? Skin tests and serum specific IgE tests can both give false positive results About 50% Example Positive serum specific IgE test for milk The child drinks milk with every meal What do these test results mean? Broad screening should NOT be done without history of reaction because of the high rate of false positives

21 Skin Prick Testing Photos with patient permission

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23 Test Results Negative skin test or serum specific IgE means the IgE antibody is not present (>95% specific) Positive skin test or specific IgE Indicates that the IgE antibody is present Does NOT necessarily mean that patient will have a reaction 90% sensitive 50% specific Larger skin test size/higher IgE level correlates with likelihood of reaction but does not tell you how severe the reaction will be

24 Did I eat something while I was pregnant that caused my child s allergy? I craved peanuts when I was pregnant PREVENTION

25 Prevention of Food Allergies Avoiding foods in pregnancy does not seem to prevent allergy, eczema, or asthma Avoiding or delaying foods in infancy does not prevent allergy for infants who are not high risk American Academy of Pediatrics Clinical Report January 2008;

26 Prevention of Food Allergies High-risk children - parent or siblings with food allergy Breast milk or hyrdolyzed infant formula until 4 months of age Soy formula likely doesn t prevent allergies Delay introduction of solids until 4 6 months of age No reason to delay introduction past this time Okay to include foods that are considered to be highly allergic such as fish, eggs and foods containing peanut protein. American Academy of Pediatrics Clinical Report January 2008;

27 Natural History of Food Allergy Most children with food allergies will eventually tolerate milk, egg, soy and wheat The age that most children outgrow the allergy varies by food If initial serum specific IgE (sige) level for a food is high, they are less likely to outgrow the allergy Hourihane, 1998; Sampson, 2004; Boyce, 2010; Wasserman, 2011

28 Food Challenge Performed to determine tolerance Conducted in an allergist s office where emergency equipment is available Skin prick test and serum specific IgE test results meet criteria to qualify for a challenge Patient is fed the food in increasing amounts watching for a reaction

29 Fatalities in Anaphylaxis Food anaphylaxis is the leading cause of anaphylaxis treated in emergency department 30,000 cases per year deaths per year Peanut, tree nut and seafood account for most of these reactions Cannot be predicted by past reactions Sampson et. al. Pediatrics :1601-8

30 Fatal Food-Induced Anaphylaxis 32 cases of fatal anaphylaxis reviewed Most were teens or young adults Peanuts and tree nuts caused >90% of reactions 2/3 of the patients had asthma Most did not have epinephrine available or did not use it Bock SA, et al. Fatalities due to anaphylactic reactions to food. J Allergy Clin Immunol 2001;107:

31 Key Point: Benadryl will NOT block anaphylaxis A history of a mild reaction does not mean that future reactions will be mild Consider an Epi Pen for all at risk of anaphylaxis It is never wrong to use the Epi Pen When you are considering using the Epi Pen.. use it! Sampson, H., et. al., 2007

32 MANAGEMENT

33 Management It Takes A TEAM No cure for food allergies Strict avoidance May lead to nutrition consequence Careful diagnosis of non-ige mediated allergy Future treatment Anti-IgE monoclonal antibody Allergen immunotherapy 3 forms under investigation: oral, sublingual and epicutaneous

34 Other Related Diagnosis Cow s Milk-Protein Allergy (CMP) Eosinophilic Esophagitis Food Protein-Induced Enterocolitis Syndrome (FPIES)

35 Management It Takes A TEAM Accurate diagnosis of food allergens Assessment of nutrition status Institution of elimination diet Prevention of adverse reactions Proper emergency action plan Treatment of associated atopic disorders

36 Management It Takes A Team Ongoing care by dietitian Monitoring of nutrition status and growth Education Ongoing care by allergist Monitoring for development of tolerance Ongoing care by gastroenterologist Monitoring for remission of symptoms

37 NUTRITION & GROWTH ASSESSMENT

38 Nutrition Assessment Growth Primary nutrition concern for all children: Poor growth History of weight gain & growth Current weight gain & growth Assessment of body composition Intake/Feeding History Distribution of fat, protein and carbohydrate Vitamin and mineral intake Barriers to meeting intake needs Current Intake Collection: 24 hour recall or 3day food record Type & volume of food & liquid Formula or breast milk, vitamin supplementation, or other supplementation

39 Carbohydrates Protein Fat Fiber Water Vitamins and Minerals Calcium Iron Vitamin D Key Nutrients

40 Distribution of Calories Fat Protein Carbohydrate Fat Protein Carbohydrate Appropriate distribution of calories Example: Toddler with age appropriate beverage & variety of solids Inappropriate distribution of calories Example: Toddler drinking rice milk & eating few foods

41 Health Risks of Poor Nutrition Deficient Nutrient Calories Protein Fat Iron Calcium & Vitamin D Zinc, Vitamins A, C, & E Zinc Vitamin K Health Risk Malnutrition, underweight, obesity Low muscle mass Poor immune function Essential fatty acid deficiency Anemia Poor endurance Rickets Osteomalacia Poor wound healing Altered taste Poor appetite Poor blood clotting

42 Clinical Signs of Nutrition Status Height/weight Fluid status Fat stores Muscle mass Skin, nails, hair, teeth, lips, gums Energy level

43 Serum Measures of Nutrition Status Iron stores Hemoglobin, hematocrit, ferritin, iron, TIBC Immune status Total lymphocyte count Stores of specific vitamins and minerals Zinc, folate, vitamin D, etc. Nutrition labs should be drawn if: Clinical signs of poor nutrition Avoiding one or more food groups Poor protein intake Recommended by dietitian

44 Diet History 24 hour recall 3 day food record Formula use Supplement use Food habits Household food restrictions Recent diet changes

45 Nutrient Intake Standards Based on the Dietary Reference Intakes (DRIs) Recommendations for calories, fat, protein, vitamins, minerals, and trace elements Based on current research Reflect the benefits of adequate nutrition (not just prevention of deficiency) Most recent update January 2011 Increased calcium and vitamin D requirements Complete DRI tables available online RIs/~/media/Files/Activity%20Files/Nutrition/DRIs/5_ Summary%20Table%20Tables%201-4.pdf

46 Growth Assessment Growth charts 0-24 months = WHO growth chart 2-20 years = CDC growth chart Weight Length or Height Weight for length or BMI for age Head circumference (under age 2) % ideal body weight Growth velocity Z-scores

47 Growth Velocity Comparison of growth for two girls with the same weight and length at 10.5 months Normal growth rate Deceleration in growth rate

48 NUTRITION AND FOOD ALLERGIES

49 Impact of Food Allergies Restricting major food groups means missing important nutrients 49

50 Nutrition Risk At least 25% will have micronutrient deficiencies Risk increases with additional problems Picky eating Feeding difficulties Social concerns Poor growth Financial concerns

51 Nutrition Risk Important to identify Red Flags Growth concerns More than 1 food allergy Or avoiding complete food group such as milk Concerns with feeding history Clinical signs of deficiency on physical exam Altered nutrition related labs

52 Food Elimination Diet The Bottom Line How many foods are they avoiding? Is it feasible to meet nutrient goals? Where is supplementation needed? Special formula Vitamin and/or mineral supplementation Oil supplementation

53 Key Micronutrients Provided by Food Allergens Allergen Micronutrients Provided Alternative Food Substitutes Milk Soy vitamin A, vitamin B 1, vitamin B 2 (riboflavin), vitamin B 12, vitamin D, vitamin B 5 (pantothenic acid), calcium, magnesium, selinium, zinc, potassium, phosphorus thiamin, vitamin B 2 (riboflavin), pyridoxine, folic acid, calcium, phosphorus, magnesium, iron, zinc meats, legumes, whole grains, nuts, mushrooms, fortified foods/beverages (fortified with B vitamins, calcium, and vitamin D), fish, bright yellow and orange vegetables meats, legumes, enriched whole grain bread products, egg, nuts, peas, seeds, milk, dried fruit Wheat thiamin, vitamin B 2 (riboflavin), niacin, iron, zinc, selenium, chromium, folic acid if fortified alternative fortified grains (barley, rice, oat, corn, rye, quinoa, amaranth, farina), soybean, legumes, egg, milk, nuts, seeds, apples, banana, spinach and potatoes Egg vitamin B 12, vitamin B 2 (riboflavin), vitamin B 5 (pantothenic acid), biotin, selenium, iron, folic acid, vitamin E, chromium meats, legumes, beans, lentils, whole grains, nuts, leafy green vegetables, fish, dried fruit

54 Key Micronutrients Provided by Food Allergens Allergen Micronutrients Provided Alternative Food Substitutes Peanuts/ Tree nuts vitamin E, biotin, copper, folic acid, niacin, magnesium, manganese, chromium whole grains, vegetable oils, soybean, egg, other legumes Fish/ Shellfish vitamin B 6, vitamin E, niacin, phosphorus, selenium, omega-3 fatty acids, folic acid, copper, zinc, potassium, vitamin A fortified whole grains, meats, oils, soybean, seeds, nuts, milk, egg

55 NUTRITION INTERVENTION

56 Intervention Identification of nutrition problems Identification of other potential referrals Establish nutrition goals Provide targeted nutrition interventions Evaluate outcomes/reassess nutrition Revise nutrition plan Establish ongoing monitoring Nutrition education

57 Grocery Shopping Cooking Socializing Travel/Vacations Eating Out Family Relationships Lotions, Pet foods etc. Impact of the Allergy Restricted Diet

58 Education Education is the cornerstone for compliance and a nutritionally adequate diet How to read food labels (every time!!) Forms of food/ingredients to avoid Foods/ingredients to include Substitutions/alternatives for nutrient goals Meal and snack planning Cross-contact Tips for dining out Recipes Resources and Support Groups

59 Food Allergen Labeling & Consumer Protection Act Effective January 1, 2006 Identify 8 major food allergens Milk, Egg, Peanut, Tree Nut, Fish, Shellfish, Wheat and Soy Identify presence in spices, flavorings, etc. Precautionary labeling May contain or Processed on is voluntary

60 Gluten Free Food Allergen Labeling & Consumer Protection Act Gluten free regulated starting August 2014 Must contain less than 20 parts per million of gluten May still contain a small amount of wheat Patients must read ingredient list Gluten free labeling is optional

61 Common Sources of Hidden Food Allergens Egg Milk Nuts Soy Wheat Rice Pasta Bread Cereals Bread/ Waffles Bread Cereals Egg Rolls Muffins/ Cake Egg Beaters Candy Marshmallows Waffles Candy/ Chocolate Frozen Desserts Cakes/ Cookies Frozen Desserts Cereal Gluten Free Products Baby Food Bread Crackers Soy Sauce Cake Low Fat Beef Franks Canned Tuna Nut Butters Chicken Hot Dogs Processed Meats Sauces/ Chili Bouillon Cubes Low Fat Beef Franks Chicken Hot Dogs Modified Food Starch Muffin Mixes Waffles Soup

62 Milk Substitutes/Beverages Whole milk is a good source of: Calories Fat Protein Calcium Vitamin D Especially for 1 year olds Need fat for brain development Calories for growth Texture of meat may be difficult to eat

63 Milk Substitutes/Beverages Nutrients per 8 oz. Whole Milk Soy Milk Almond Milk Rice Milk Calories to to Protein (g) 8 7 to 11 1 to 5* 1* Carbohydrate (g) 11 7 to 13 7 to 8 23 Fat (g) to to Saturated fat (g) 5 0 to Calcium (mg) to to Vit D (IU) to to

64 Milk Substitutes/Beverages Nutrients per 8 oz. Whole Milk Hemp Milk Almond Coconut Blend Coconut, Almond, & Chia Blend Calories Protein (g) 8 2 to 3* <1* <1* Carbohydrate (g) Fat (g) 8 5 to Saturated fat (g) Calcium (mg) Vit D (IU) to

65 Milk Substitutes/Beverages Key takeaways If allergic to milk Choose soy milk Add fats to food If allergic to milk and soy 1 year old Elecare Jr, Neocate Jr, EO28 Splash May continue infant formula or breast milk Consult the dietitian 2 years old and eating meat may try other milk substitutes With any substitutes, must read the label for calcium and vitamin D content

66 Nutritionally Complete Formulas Standard Milk based Enfamil Infant, Similac Infant (19 calories/ounce), Pediasure Soy Soy based Enfamil Prosbee, Good Start Soy, Bright Beginnings Soy Drink Partially hydrolyzed Proteins are partially broken down NOT hypoallergenic Good Start Gentle, Enfamil Gentlease

67 Nutritionally Complete Formulas Extensively hydrolyzed Proteins are extensively broken down, but still peptides Considered to be hypoallergenic Similac Alimentum, Enfamil Nutramigen, Pediasure Peptide Elemental Single amino acids Neocate Infant, Elecare Infant, Neocate Jr, Elecare Jr, EO28 Splash

68 Micronutrient Supplementation Must be chewable, not gummy Must contain iron Age appropriate serving Complete Chewable Multivitamin with Iron (many brands) Nature s Plus Animal Parade Gold Children s Liquid Nature s Plus Animal Parade Sugar Free Children s Multivitamin Vitaflo FruitiVits Powder Multivitamin Nano VM Powder Nature s Plus Source of Life Power Teen

69 Guidelines for Baked Allergens Must be baked to a high temperature Structure change Cooked thoroughly Home made should be baked in individual serving size Muffin, cupcake (not bread or cake) Commercial bread is okay Must be mixed into the product Milk allergy use milk free chocolate chips Allergen must be a small amount Not in the first 3 ingredients for commercial products 20 ml milk or less per serving (challenge) ¼ egg or less per serving (challenge) Groetch, M. & Nowak-Wegrzyn, A. Practical approach to nutrition and dietary intervention in pediatric food allergy. Pediatric Allergy & Immunology, 2013, 24: Nowak-Wegrzyn, A. & Fiocchi, A. Rare, medium, or well done? The effect of heating and food matrix on food protein allergenicity. Current Opinion in Allergy and Clinical Immunology, 2009, 9:

70 APPLICATION

71 SAMPLE MENU: 1 TO 3 YEAR OLD CHILD (DIET 1)

72 DIET 1 ANALYSIS Nutrient % Goal Calories 1490 >100% Protein 47 grams 360% Fat 55 grams 33% total calories Calcium 1100 milligrams 157% Vitamin D 203 IU 34% Iron 9.9 milligrams 141% Zinc 8.9 milligrams 297%

73 SAMPLE MENU: 1 TO 3 YEAR OLD CHILD WITH MILK, EGG AND PEANUT ALLERGY (DIET 2) Problem Nutrients: Calories Protein Fat Calcium Vitamin D Iron

74 Diet 2 Analysis Nutrient % Goal Calories % Protein 5 grams 41% Fat 2 grams 6% total calories Calcium 98 milligrams 14% Vitamin D 20 IU 3% Iron 4 milligrams 59% Zinc 2.6 milligrams 87%

75 REVISED MENU: 1 TO 3 YEAR OLD CHILD WITH MILK, EGG AND PEANUT ALLERGY (DIET 3)

76 DIET 3 ANALYSIS Nutrient % Goal Calories 1360 >100% Protein 42 grams 321% Fat 49 grams 32% total calories Calcium 754 milligrams 108% Vitamin D 285 IU 48% Iron 10 milligrams 147% Zinc 6 milligrams 201%

77 Finding allergen free foods Keep it Simple: Single ingredient foods Intranet: Online grocery stores Learn to Read the Food Label Recipes, recipes and more recipes Food Manufactures Websites Regular and Specialty Grocery Stores

78 ENTERAL NUTRITION

79 Straight forward Enteral Nutrition If child with Cow s milk protein If child with other protein allergies Formula intolerance Often secondary to food allergies Transition to protein hydrolysate/elemental formula Often diagnosed retrospectively

80 PARENTERAL NUTRITION

81 Minimal data Egg Allergy Soy Allergy Parenteral Nutrition

82 Parenteral Nutrition-Case Reports Variety of allergies to PN More common in children Manifestations Skin rashes (most common) Dyspnea, cyanosis, nausea, vomiting, headache, flushing, fever, chest pain Can occur First administration After several days After reinstitution following hiatus

83 Parenteral Nutrition-Case Reports Attributed to: IV fat emulsions Crystalline amino acid solutions Multivitamin mixtures Latex stopper on the IV fat emulsion

84 Parenteral Nutrition- Management If reactions occur, PN should be stopped Appropriate drug treatment for reaction If severe and requires ongoing PN Multidisciplinary approach Allergist, pharmacist, nutrition-support physician, dietitian Two approaches when mild: SPT of PN components and removal of offending agent Identify offending agent through trial and error When severe: IV desensitization in the ICU has been described Unclear if this method actually worked

85 Parenteral Nutrition- Management IV Iron Cause significant allergic reactions Iron dextran, sodium ferric gluconate complex in sucrose and iron sucrose Lowest risk iron sucrose Least expensive iron dextran Test doses

86 Question #1 A 7-year-old boy with an enterocutaneous fistula develops an urticarial rash the day that he is started on parenteral nutrition. All of the following constituents of his parenteral nutrition could cause the rash EXCEPT: A. Intravenous fat emulsion B. Amino acid solution C. Pediatric Multivitamin solution D. Dextrose

87 Question #2 An 18-month-old vegetarian girl with presumed milk and soy protein allergy is drinking 32 ounces of enriched almond milk per day. She also eats rice, wheat, corn, fruits, and vegetables but does not consume any egg or meat products. She does not receive any vitamin or mineral supplementation. You are concerned about her intake of all of the following EXCEPT: A. Fat B. Vitamin D C. Energy D. Zinc

88 Question #3 A 6-year-old Asian boy is seen by a dietitian for follow-up nutritional assessment and education. His parents report he is allergic to milk, soy, and peanuts. He has a history of anaphylaxis while eating peanut butter a year ago. His current intake includes tofu stirfry and milk chocolate candy bars. Parents report he eats these foods at least once a week without any problems. He does not drink a milk substitute. All of the following must be done or considered at this visit EXCEPT: A. Assessment of growth and nutrient intake B. Suggesting an ageappropriate beverage C. Recommending follow-up with allergist as patient is tolerating milk and soy D. Suggesting food challenge of peanut butter at home

89 Question #4 A 6-month-old breastfed infant has significant vomiting and diarrhea within hours of being given a bottle of cow s milk formula. His mother reports that this has happened each time he has been fed the formula. She denies any skin rashes. A serum lab for IgE directed against cow s milk protein is negative. All of the following are true about this child EXCEPT: A. This consistent with IgEmediated anaphylaxis. B. This is most likely food protein-induced enterocolitis syndrome C. Cow s milk protein must be eliminated from the child s diet D. In addition to breastfeeding, a protein hydrolysate formula may be appropriate

90 FOOD ALLERGY RESOURCES

91 FOOD ALLERGY RESOURCES FARE School Food Allergy Program free to schools in the USA Resources for dining out, including a restaurant training program FAAN Anaphylaxis video National Annual Conference

92 FOOD ALLERGY RESOURCES Children s Hospital of Wisconsin Search: teaching sheets Search key words: allergy, asthma, eczema Medical I.D. Feeding Your Baby 0-12 months Feeding Your Toddler 1-3 years Calcium and Vitamin D in Your Child s Diet Increasing Iron in Your Child s Diet Increasing Fiber in Your Child s Diet Eosinophilic Esophagitis Food Allergy Overview

93 FOOD ALLERGY RESOURCES Academy of Nutrition and Dietetics Website: U.S.D.A. Food and Nutrition Information Center MedicAlert Foundation International Website: ID on me Medic Alert Bracelets Website: The American Academy of Pediatrics Website:

94 COMMON BRANDS OF ALLERGEN FREE FOODS

95 "If we could give every individual the right amount of nourishment and exercise, not too little and not too much, we would have found the safest way to health." Hippocrates