Clinical Practice Guidelines for Healthy Eating for the Prevention and Treatment of Metabolic and Endocrine Diseases in Adults: Cosponsored by the American Association of Clinical Endocrinologists/The American College of Endocrinology and the Obesity Society

      Abbreviations

      1,25(OH)2D
      1,25-dihydroxyvitamin D
      25(OH)D
      25-hydroxyvitamin D
      A1c
      hemoglobin A1c
      AACE
      American Association of Clinical Endocrinologists
      ADA
      American Diabetes Association
      AHA
      American Heart Association
      AI
      adequate intake
      ALA
      alpha-linoleic acid
      BEE
      basal energy expenditure
      BEL
      “best evidence” rating level
      BMI
      body mass index
      BMR
      basal metabolic rate
      BP
      blood pressure
      CCM
      Chronic Care Model
      CCS
      consecutive case studies
      CHD
      coronary heart disease
      CI
      confidence interval
      CKD
      chronic kidney disease
      CPG
      clinical practice guideline
      CSS
      cross-sectional study
      CV
      cardiovascular
      CVD
      cardiovascular disease
      D3
      cholecalciferol
      DASH
      Dietary Approaches to Stop Hypertension
      DBP
      diastolic blood pressure
      DHA
      docosahexaenoic acid
      DM
      diabetes mellitus
      DRI
      dietary reference intake
      DV
      daily value
      EAA
      essential amino acid
      EFA
      essential fatty acid
      EI
      energy intake
      EL
      evidence level
      EPA
      eicosapentaenoic acid
      ESKD
      end-stage kidney disease
      FDA
      U.S. Food and Drug Administration
      GDM
      gestational diabetes mellitus
      GFR
      glomerular filtration rate
      GI
      glycemic index
      HBV
      high-biological-value
      HDL-C
      high-density-lipoprotein cholesterol
      HFCS
      high fructose corn syrup
      HP/LC
      high-protein/low-carbohydrate
      HR
      hazard ratio
      IOM
      Institute of Medicine
      LCMP
      low-calorie meal plan
      LDL-C
      low-density-lipoprotein cholesterol
      LoBAG
      low biologically available glucose
      MNRCT
      meta-analysis of nonrandomized prospective or case-controlled studies
      MNT
      medical nutrition therapy
      MRCT
      meta-analysis of randomized controlled trials
      MUFA
      monounsaturated fatty acid
      MVI
      multivitamin
      NCEP
      National Cholesterol Education Program
      NE
      no evidence (theory, opinion, consensus, and review)
      NIH
      National Institutes of Health
      NHANES
      National Health and Nutrition Examination Survey
      NRCT
      nonrandomized controlled trial
      PCOS
      polycystic ovarian syndrome
      PCS
      prospective cohort study
      PPG
      postprandial glucose
      PNV
      prenatal vitamin
      PTH
      parathyroid hormone
      PUFA
      poly-unsaturated fatty acid
      Q
      question
      R
      recommendation
      RCCS
      retrospective case-control study
      RCT
      randomized controlled trial
      RD
      registered dietician
      RDA
      recommended dietary allowance
      REE
      resting energy expenditure
      RMR
      resting metabolic rate
      RR
      relative risk
      RRT
      renal replacement therapy
      RYGB
      Roux-en-Y gastric bypass
      SBP
      systolic blood pressure
      SCR
      single-case report
      SS
      surveillance study (registries, surveys, epidemiologic)
      SSB
      sugar-sweetened beverage
      T1DM
      type 1 diabetes mellitus
      T2DM
      type 2 diabetes mellitus
      TC
      total cholesterol
      TEE
      total energy expenditure
      TG
      tri-glyceride
      TLC
      therapeutic lifestyle changes
      TOS
      The Obesity Society
      TV
      television
      TUL
      tolerable upper limit
      USDA
      United States Department of Agriculture
      VLCMP
      very low-calorie meal plan
      WHO
      World Health Organization

      1. INTRODUCTION

      The American Association of Clinical Endocrinologists (AACE) and The Obesity Society (TOS) are professional organizations dedicated to improve the lives of patients with endocrine and metabolic disorders. Chronic diseases demand treatment, but a focus on primary, secondary, and tertiary prevention strategies is important as well. Central to this approach is behavior modification to achieve consistent healthy eating and physical activity. Yet, to date there is no evidence-based clinical practice guideline (CPG) to define the standards of care for healthy eating in the management and prevention of metabolic and endocrine disorders. This joint effort of AACE and TOS addresses this deficit.
      For most clinical endocrinologists, nutrition education is not structured. Many of the endocrinology training programs in the United States lack a dedicated nutrition curriculum. The same problem affects physicians with a focus of practice in bariatric medicine (
      • McClave S.A.
      • Mechanick J.I.
      • Bistrian B.
      • et al.
      What is the significance of a physician shortage in nutrition medicine?.
      [EL4, NE];
      • McClave S.A.
      • Mechanick J.I.
      • Kushner R.F.
      • et al.
      Compilation of recommendations from summit on increasing physician nutrition experts.
      [EL4, NE]). As a result, nutritional counseling and management for our patients is often delegated to other health care professionals.
      There are many obstacles that preclude patient access to nutritional education. Federal institutions have not paid for nutrition education except for a limited number of conditions, including medical nutrition therapy (MNT) for diabetes mellitus (DM) and nutrition counseling for chronic kidney disease (CKD) stage 5. Although Medicare has recently approved counseling for obesity, most overweight patients or patients with obesity, dyslipidemia, polycystic ovarian syndrome (PCOS), hypertension, osteopenia and osteoporosis, hyperuricemia, earlier stages of CKD, eating disorders, malnutrition, and prediabetes are marginalized from this important component of health care.
      Other obstacles to implementing healthy eating strategies on a large scale include:
      • unawareness of the importance of health promotion and wellness care in the general population to prevent disease, including endocrine and metabolic disorders,
      • the relative paucity of healthy nutritional principles and eating patterns taught in American schools, higher education institutions, and even workplaces,
      • the relative scarcity and increased expense of healthy foods,
      • the easy accessibility, low cost, and palatability of less-healthy foods,
      • mass-media marketing of foods with low nutritional value,
      • lack of oversight of food marketing, and inadequate and/or ineffective food policies,
      • the perishability of foods, increased need for preservatives, and decreased awareness of food safety,
      • the variability of nutrient-gene interactions (nutrigenomics and nutrigenetics), and
      • transcultural factors, including religious, social, ethnic, and economic factors, as well as individual food preferences, culinary styles, and belief systems.
      This CPG proposes an evidence-based, standardized context for healthy eating recommendations. Throughout this document, the word “diet” is avoided, and the terms “meal plan” (what patients are taught to eat) and “eating or dietary pattern” (the structure or composition of the meals) are preferred instead. This CPG does not formally address healthy eating for pediatric or hospitalized patients but makes reference to them when appropriate.

      2. METHODS

      The AACE Board of Directors mandated a CPG on healthy eating for the prevention and treatment of metabolic and endocrine diseases in adults. The project was approved for co-authorship with TOS by the leadership of both organizations. This CPG was developed in accordance with the AACE Protocol for Standardized Production of Clinical Practice Guidelines – 2010 Update. Reference citations in the text of this document include the reference number, numerical descriptor (evidence level; EL 1-4), and semantic descriptor (see Table 1, Table 2, Table 3, Table 4). Recommendations are assigned Grade levels based on the supporting clinical evidence and subjective factors. The format of this CPG is based on specific and relevant clinical questions. All primary writers have made disclosures regarding multiplicities of interest. In addition, all primary writers are credentialed experts in the fields of nutrition, endocrinology, or both. This CPG has been reviewed and approved by the primary writers, other invited experts, the AACE Publications and Nutrition Committees, and the AACE Board of Directors prior to submission for peer review in Endocrine Practice. This CPG has also been approved by selected members of TOS prior to submission for peer review in Obesity, The Official Journal of TOS. This CPG expires in 2016.
      Table 12010 AACE Protocol for Production of Clinical Practice Guidelines. Step I: Evidence Rating
      1Meta-analysis of randomized controlled trials (MRCT)
      1Randomized controlled trials (RCT)
      2Meta-analysis of nonrandomized prospective or case-controlled trials (MNRCT)
      2Nonrandomized controlled trial (NRCT)
      2Prospective cohort study (PCS)
      2Retrospective case-control study (RCCS)
      3Cross-sectional study (CSS)
      3Surveillance study (registries, surveys, epidemiologic study, retrospective chart review, mathematical modeling of database) (SS)
      3Consecutive case series (CSS)
      3Single case reports (SCR)
      4No evidence (theory, opinion, consensus, or review) (NE)
      Abbreviations: AACE = American Association of Clinical Endocrinologists. 1 = strong evidence; 2 = intermediate evidence; 3 = weak evidence; 4 = no evidence.
      Adapted from Mechanick et al. Endocr Pract. 2010;16:270-283.
      Table 22010 AACE Protocol for Production of Clinical Practice Guidelines. Step II: Evidence Analysis and Subjective Factors
      Study designData analysisInterpretation of results
      Premise correctnessIntent-to-treatGeneralizability
      Allocation concealment (randomization)Appropriate statisticsLogical
      Selection biasIncompleteness
      Appropriate blindingValidity
      Using surrogate end points (especially in “first in class” intervention)
      Sample size (beta error)
      Null hypothesis versus Bayesian statistics
      Abbreviation: AACE = American Association of Clinical Endocrinologists.
      Adapted from Mechanick et al. Endocr Pract. 2010;16:270-283.
      Table 32010 AACE Protocol for Production of Clinical Practice Guidelines. Step III: Grading of Recommendations – How Different Evidence Levels Can be Mapped to the Same Recommendation Grade
      Starting with the left column, BEL, subjective factors, and consensus map to recommendation grades in the right column. When subjective factors have little or no impact (“none”), then the BEL is directly mapped to recommendation grades. When subjective factors have a strong impact, then recommendation grades may be adjusted up (“positive” impact) or down (“negative” impact). If a two-thirds consensus cannot be reached, then the recommendation grade is D. NA regardless of the presence or absence of strong subjective factors, the absence of a two-thirds consensus mandates a recommendation grade D.
      BELSubjective factor impactTwo-thirds consensusMappingRecommendation grade
      1NoneYesDirectA
      2PositiveYesAdjust upA
      2NoneYesDirectB
      1NegativeYesAdjust downB
      3PositiveYesAdjust upB
      3NoneYesDirectC
      2NegativeYesAdjust downC
      4PositiveYesAdjust upC
      4NoneYesDirectD
      3NegativeYesAdjust downD
      1, 2, 3, 4NANoAdjust downD
      Abbreviations: AACE = American Association of Clinical Endocrinologists; BEL = best evidence level; NA = not applicable.
      a Starting with the left column, BEL, subjective factors, and consensus map to recommendation grades in the right column. When subjective factors have little or no impact (“none”), then the BEL is directly mapped to recommendation grades. When subjective factors have a strong impact, then recommendation grades may be adjusted up (“positive” impact) or down (“negative” impact). If a two-thirds consensus cannot be reached, then the recommendation grade is D. NA regardless of the presence or absence of strong subjective factors, the absence of a two-thirds consensus mandates a recommendation grade D.
      Table 42010 American Association of Clinical Endocrinologists Protocol for Production of Clinical Practice Guidelines. Step IV: Examples of Qualifiers that may be Appended to Recommendations
      Cost effectiveness
      Risk-benefit analysis
      Evidence gaps
      Alternative physician preferences (dissenting opinions)
      Alternative recommendations (“cascades”)
      Resource availability
      Cultural factors
      Relevance (patient-oriented evidence that matters)
      Adapted from Mechanick et al. Endocr Pract. 2010;16:270-283.
      Clinical questions are labeled “Q” and recommendations are labeled “R”. Recommendation grades are based on four intuitive levels: (grades A [strong], B [intermediate], and C [weak]) or expert opinion when there is a lack of conclusive clinical evidence (grade D). The “best evidence” rating level (BEL), which corresponds to the best conclusive evidence found in the discussion section in the appendix, accompanies the recommendation grades in the Executive Summary. There are also four intuitive levels of evidence: 1 = strong, 2 = intermediate, 3 = weak, and 4 = no evidence. Comments may be appended to recommendations regarding relevant subjective factors that may have influenced the grading process. The consensus level of experts for each recommendation may also be explicitly provided in appropriate instances. Thus, the process leading to a final recommendation and grade is not dogmatic but rather incorporates a complex expert integration of objective and subjective factors meant to reflect optimal real-life clinical decision-making to enhance patient care. Where appropriate, cascades of recommendations are provided (settings with limited resources, unique patient attributes, etc. (
      • Mechanick J.I.
      • Camacho P.M.
      • Cobin R.H.
      • et al.
      American Association of Clinical Endocrinologists Protocol for Standardized Production of Clinical Practice Guidelines--2010 update.
      ) [EL4, NE]).

      3. EXECUTIVE SUMMARY

      3.Q1 What is Healthy Eating?

      3.Q1.1 General Recommendations for Healthy Eating and Disease Prevention

      • R1. All patients should be instructed on healthy eating and on proper meal planning by qualified health care professionals (Grade A, BEL 1). Essential macronutrients and micronutrients, fiber, and water should be provided by well-chosen foods and beverages that can be enjoyed and constitute a healthy eating pattern. Macronutrients should be recommended in the context of a calorie-controlled meal plan (Grade A, BEL 1). All patients should also be counseled on other ways to achieve a healthy lifestyle, including regular physical activity (150 minutes or more per week), ways to avoid a sedentary lifestyle, appropriate sleep time (6 or more hours every night), and budgeting time for recreation or play, stress reduction, and happiness (Grade A, BEL 1).

      3.Q1.2 Healthy Macronutrient Intake

      • R2. In a healthy eating meal plan, carbohydrates should provide 45 to 65% of ingested energy, with due diligence to limit simple sugars or foods that have a high glycemic index (GI). Regardless of the macronutrient mix, total caloric intake must be appropriate for individual weight management goals. Patients should consume 6 to 8 servings of carbohydrates (one serving is 15 grams of carbohydrate) per day with at least half (3 to 4 servings) being from high-fiber, whole-grain products (Grade A, BEL 1). Consumption of fruits (especially berries) and vegetables (especially raw) (≥4.5 cups per day) will increase fiber, increase phytonutrient intake, and facilitate calorie control (Grade B, BEL 2). Patients should be instructed to consume whole grains in place of refined grains, which will add fiber and micronutrients to meals and help lower blood pressure (BP) (Grade A, BEL 1).
      • R3. Protein from both plant and animal sources (15 to 35% of calories depending on total intake) can replace a portion of saturated fat and/or refined carbohydrates in the meal plan to help improve blood lipids and BP (Grade A, BEL1). The meal plan should include a maximum of 6 ounces per day of reduced-fat animal protein to increase the nutrient-to-calorie ratio (Grade B, BEL 1). Reduced-fat dairy (2 to 3 servings per day) should be recommended as a source of high-quality protein for patients who are not intolerant or allergic to lactose because it lowers BP and helps reduce weight while also providing important micronutrients (Grade A, BEL 1). Plant protein (e.g., pulses, including beans, lentils, and some nuts; and certain vegetables, including broccoli, kale, and spinach) should be emphasized in meal planning, as it is not commonly consumed in Western meals; plant proteins confer many health benefits, including improved blood lipid levels and BP (Grade B, BEL 2).
      • R4. Patients should be counseled to consume unsaturated fats from liquid vegetable oils, seeds, nuts, and fish (including omega-3 fatty acids) in place of high-saturated fat foods (butter and animal fats), providing 25 to 35% of daily calories to reduce the risk for cardiovascular disease (CVD) (Grade A, BEL 1). It should be recommended that patients consume natural foods high in monounsaturated fat, such as olive oil in the Mediterranean dietary pattern, since this is strongly associated with improved health outcomes (Grade A, BEL 1). It should be recommended that patients eat at least 2 servings of cold-water, fatty fish (such as salmon or mackerel) every week because they contain greater amounts of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (Grade B, BEL 2)

      3.Q1.3 Healthy Micronutrient Intake

      • R5. With the exception of proven therapies for documented specific vitamin deficiency states or diseases, or pregnancy, there are insufficient data to recommend supplemental vitamin intake above the recommended dietary allowances (RDA) (Grade D, BEL 4). Vitamin E supplementation to decrease cardiovascular (CV) events or cancer is not recommended (Grade B, BEL 2). Lifelong regular follow-up and individualized therapy are recommended in diseases known to cause intestinal malabsorption (e.g., after malabsorptive bariatric surgery, ileocolic resection, short bowel syndrome, celiac disease, inflammatory bowel disease, exocrine pancreatic insufficiency, CKD, and chronic liver disease) to detect and treat vitamin and mineral deficiencies (Grade B, BEL 2).
      • R6. Vitamin B12 levels should be checked periodically in older adults and patients on metformin therapy (Grade A, BEL 1). With the exception of early treatment of patients with neurologic symptoms, pernicious anemia, or malabsorptive bariatric surgery requiring parenteral (intramuscular or subcutaneous) vitamin B12 replacement, patients with vitamin B12 deficiency can generally be treated with oral vitamin B12 (1,000 μg per day of oral crystalline cobalamin) and may benefit from increasing the intake of vitamin B12 in food (Grade A, BEL 1).
      • R7. The prevalence of vitamin D deficiency and insufficiency warrants case finding by measurement of 25-hydroxyvitamin D (25[OH]D) levels in populations at risk, including institutionalized elderly patients, people with hyperpigmented skin, and people with obesity (Grade B BEL 2). Older adults, people with increased skin pigmentation, and those exposed to insufficient sunlight should increase vitamin D intake from vitamin D-fortified foods and/or supplements to at least 800 to 1,000 international units (IU) daily (Grade A, BEL 1)

      3.Q2 What Nutritional Recommendations are Appropriate for Weight Management?

      3.Q2.1 Approach to Overweight and Obesity

      • R8. Overweight and obesity should be managed as a long-term chronic disease (Grade A, BEL 1). Overweight and obesity should be managed using a multidisciplinary team approach (Grade A, BEL 1). Nutrition counseling for overweight and obesity should be aimed to decrease fat mass and also to correct adipose tissue dysfunction (adiposopathy) (Grade A, BEL 1). Adult feeding behavior is solidly rooted from childhood, so it is important to counsel adult patients to include their families, especially their children, in healthy eating behavior changes (Grade B, BEL 2). Nutrition counseling should be culturally, linguistically, and educationally provided to meet individual patient needs (Grade D, BEL 4).
      • R9. The weight-loss goal for overweight or obese patients is 5 to 10% of current body weight over the ensuing 6 to 12 months. This goal is perennial until an acceptable body mass index (BMI) is achieved (Grade A, BEL 1). Combined therapy utilizing a low-calorie meal plan (LCMP), increased physical activity, behavior therapy, and appropriate pharmacotherapy provides the most successful intervention for weight loss and weight maintenance and is also recommended as an adjunct to bariatric surgery (Grade A, BEL2. Expert panel experience and consensus).
      Adapted from Mechanick et al. Endocr Pract. 2010;16:270-283.

      3.Q2.2 Behavior Modification

      • R10. Sustained behavior modification must be achieved for long-term success with weight management. Food and activity recordkeeping should be recommended to help patients achieve the best results (Grade A, BEL 1). Behavioral group therapy is a cost-effective way of providing nutrition counseling to patients and should be incorporated into weight management treatment programs (Grade B, BEL 2). Use of portion-controlled prepackaged meals should be considered as a way to achieve a lower caloric intake (Grade A, BEL 1).

      3.Q2.3 Low-Calorie Meal Plans

      • R11. When first treating a patient with overweight or obesity, emphasis should be placed on maintaining a healthy meal plan and avoiding fad diets while including food choices from all major food groups (Grade A, BEL 2). A healthy, LCMP with a deficit of 500 to 1,000 kcal/day should be an integral part of any program aimed at achieving a total weight-loss rate of 1 to 2 pounds/week (which may include lean muscle mass as well as fat mass weight loss) (Grade A, BEL 1). All meal plans of <1,200 kcal/day should be carefully selected so that nutrient requirements are met. When particular food groups are severely restricted or omitted, the use of dietary supplements to meet nutrient requirements should be implemented (Grade D, EL 4).

      3.Q2.4 Very Low-Calorie Meal Plans

      • R12. Very low-calorie meal plans (VLCMPs) (≤800 kcal/day or ~6 to 10 kcal/kg), which can produce weight losses up to 1.5 to 2.5 kg/week and up to 20 kg in 12 to 16 weeks, may be recommended for patients with a BMI >30 kg/m2 who have significant comorbidities or who have failed other nutritional approaches to weight loss (Grade B, BEL 2). VLCMP treatment requires nutritional supplementation and medical monitoring for complications, including electrolyte imbalances, hepatic transaminase elevation, and gallstone formation, and the duration of treatment should not exceed 12 to 16 weeks (Grade A, BEL 1)

      3.Q3 What Nutritional Recommendations are Appropriate for Cardiovascular Health?

      3.Q3.1 Nutritional Strategies for Excess Fat Mass and Adiposopathy

      • R13. All patients at risk for CVD should implement healthy eating patterns, which provide calorie control, adequate nutrients, beneficial bioactive compounds, and result in weight loss or weight maintenance (Grade D, BEL 4). To help control calorie intake, patients should eat meals that are low in energy density (Grade A, BEL1). All patients should also be advised to increase caloric expenditure to at least 150 minutes of moderate-intensity activity every week (e.g., walking) or 75 minutes of vigorous-intensity activity every week (e.g., running) (Grade A, BEL 1). Successful weight loss and maintenance to decrease CV risk must include both a change in meal plan as well as frequent physical activity (Grade A, BEL 1).

      3.Q3.2 Nutritional Strategies for Dyslipidemia

      • R14. The therapeutic lifestyle changes (TLC) meal plan with viscous fiber and plant sterols and stanols is recommended for individuals with elevated low-density-lipoprotein cholesterol (LDL-C) (Grade A, BEL 1). The Mediterranean meal plan (or a TLC meal plan that provides 30 to 35% of calories from total fat with an emphasis on mono-and polyunsaturated fatty acids [PUFAs]) is recommended for individuals who have abnormal non-LDL-C lipid values (Grade A, BEL 1).

      3.Q3.3 Nutritional Strategies for Hypertension

      • R15. Attaining and maintaining a healthy body weight is recommended to prevent and treat hypertension. Obese and overweight individuals should accomplish a 10% weight loss to decrease their BP (Grade A, BEL 1). All patients should be counseled to adhere to the Dietary Approaches to Stop Hypertension (DASH) meal plan, which is high in fruits, vegetables, whole grains, and reduced-fat dairy (Grade A, BEL 1). Sodium intake should be reduced to <2,300 mg/day, and potassium intake should be increased to >4,700 mg/day with implementation of a DASH-type meal plan (Grade A, BEL 1). Sodium intake should be further reduced (<1,500 mg/day; or 3,800 mg/day of table salt) for people age 51 years and above, all people who are African American, regardless of age, and for patients who have hypertension, DM, or CKD (Grade A, BEL 1).

      3.Q4 What Nutrient Sources Should be Limited for Cardiovascular Health?

      • R16. Added sugars should be limited to <100 calories per day for women and <150 calories per day for men (Grade A, BEL 1). Sugar-sweetened beverage (SSB) intake should be reduced as an effective way to reduce added sugar intake (Grade B, BEL 2). Saturated fat intake should be limited to <7% for reduction of CVD risk (Grade A, BEL 1). It is recommended that processed red meat intake be limited to less than 2 servings per week and that lean or very lean red meat cuts be consumed while controlling for saturated fat intake (Grade B, BEL 2). Whole grain products should be substituted for refined grain products when possible, such that at least one-half of daily servings of grains are from whole grains (Grade B, BEL 2).

      3.Q5 What Nutritional Recommendations are Appropriate for Diabetes Mellitus?

      3.Q5.1 Patient Nutrition Education

      • R17. Medical nutrition therapy provided by a physician, physician extender, registered dietician (RD), and/or certified diabetes educator (CDE) is recommended for all patients with DM (Grade A, BEL 1). Patients with DM who experience difficulty achieving glycemic targets should keep a personal food diary (Grade D, BEL 4).

      3.Q5.2 Caloric and Protein Intake

      • R18. Patients with DM should consume total daily calories at amounts sufficient to attain or maintain a normal BMI of 18.5 to 24.9 kg/m2, which is generally in the 15 to 30 kcal/kg/day range, depending on level of physical activity (Grade A, BEL 1). Patients with DM should consume protein in the 0.8 to 1.0 g/kg/day range, and protein should account for about 15 to 35% of the total calorie consumption for the day (Grade C, BEL 3).

      3.Q5.3 Carbohydrate Intake

      • R19. Medical nutrition therapy should be implemented to control the glycemic response to meals and to achieve hemoglobin A1c (A1c) and blood glucose levels as close to the target range as possible without risk to the individual patient (Grade A, BEL 1). Carbohydrates should account for about 45 to 65% of the total calorie consumption for the day, including low-fat dairy products and sucrose (Grade C, BEL 3). Patients with DM should consume carbohydrate primarily from unprocessed carbohydrates, which are provided by a target of 8 to 10 servings per day of vegetables (particularly raw), fruits, and legumes, with due diligence to limit simple sugars or foods that have a high GI (Grade A, BEL 1). Regardless of the macronutrient mix, total caloric intake must be appropriate for individual weight management goals. Patients with DM should consume 20 to 35 g of fiber from raw vegetables and unprocessed grains (or about 14 g of fiber per 1,000 kcal ingested) per day (the same as the general population) (Grade B, BEL 2). Patients with type 1 DM (T1DM), or insulin- treated type 2 DM (T2DM) should synchronize insulin dosing with carbohydrate intake (Grade A, BEL 1). Patients with T2DM treated with short-acting oral hypoglycemic agents (nateglinide, repaglinide) should also synchronize carbohydrate intake with administration of these medications (Grade A, BEL 1). Patients with DM may safely consume artificial sweeteners within the guidelines of the U.S. Food and Drug Administration (FDA) (Grade D, BEL 4).

      3.Q5.4 Fat Intake

      • R20. For patients with DM, total fat intake should account for about 30% of the total daily calories (Grade B, BEL 2). Consumption of saturated fat should be less than 7% of total daily calories regardless of the serum total cholesterol level, and PUFAs should be up to 10% of the total daily calories (examples of food sources include vegetable oils high in n-6 PUFA, soft margarine, salad dressings, mayonnaise, and some nuts and seeds) (Grade B, BEL 2). The n-3 PUFAs are most desirable, and dietary recommendations for EPA and DHA can be achieved with two or more servings of fresh fish per week (Grade B, BEL 2). In patients with DM, monounsaturated fatty acids (MUFAs) should be up to 15 to 20% of the total daily calories (Grade B, BEL 2). Dietary cholesterol should be less than 200 mg/day (Grade A, BEL 1). Patients with DM should avoid consumption of trans fats (Grade C, BEL 3).

      3.Q5.5 Other Nutritional Recommendations

      • R21. There is insufficient evidence to specifically recommend a “low-GI” meal plan in patients with DM (Grade D, BEL 4). There is insufficient evidence to support the routine use of antioxidants, chromium, magnesium, and/or vanadium in patients with DM (Grade C, BEL 3).
      • R22. Patients with DM who choose to drink alcohol should ingest it with food and limit intake to 2 servings per day for men or 1 serving per day for women. Alcohol intake should not be increased for any purported beneficial effect (Grade D, BEL 4). There is insufficient evidence, based on long-term risks and benefits, to support the use of fad diets in patients with DM (Grade D, BEL 4).

      3.Q5.6 Diabetes Mellitus Prevention

      • R23. There is insufficient evidence to support nutrition changes to specifically prevent T1DM (Grade D, BEL 4). However, women with a personal or family history of T1DM who may be HLA-DR3 and DR4 carriers should be counseled on the medical evidence suggesting that the use of infant formula derived from cow’s milk in the first 6 months of life increases a baby’s risk of T1DM by stimulating antibody formation to the beta-cells (Grade B, BEL2). Patients at high risk for the development of T2DM should implement lifestyle interventions to achieve a minimum of 7% weight loss followed by weight maintenance, and a minimum of 150 minutes of weekly physical activity, similar in intensity to brisk walking (Grade A, BEL 1).

      3.Q6 What Nutritional Recommendations are Appropriate for Chronic Kidney Disease?

      3.Q6.1 General Approach

      • R24. Patients with CKD should have a meal plan low in protein, sodium, potassium, and phosphorus, which slows the progression of kidney disease (Grade A, BEL1). All patients with CKD should receive nutrition education by qualified health care professionals (Grade A, BEL 1).

      3.Q6.2 Protein Requirements

      • R25. In CKD stages 1, 2, or 3, protein intake should be limited to 12 to 15% of daily calorie intake or 0.8 g of high-biological-value (HBV) protein/kg body weight/day (Grade A, BEL 1). In CKD stage 4, protein intake should be reduced to 10% of daily calorie intake or 0.6 g of high-quality protein/kg body weight/day, provided an essential amino acid (EAA) deficiency does not occur (Grade A, BEL 1). For nondialyzed CKD patients with a glomerular filtration rate (GFR) <25 mL/min, 0.6 g of protein/kg body weight/day should be prescribed, with at least 50% of the protein intake from HBV sources to ensure a sufficient amount of EAAs (Grade A, BEL 1). For patients with CKD stage 5 or patients on renal replacement therapy (RRT), protein intake should be 1.3 g/kg/day (peritoneal dialysis) or 1.2 g/kg/day (hemodialysis) (Grade A, BEL 1). Urinary protein losses in the nephrotic syndrome should be replaced, and a low-normal protein dietary reference intake (DRI) of 0.8 to 1.0 g/kg body weight/day should be recommended (Grade C, BEL 3).
      • R26. Patients with CKD stages 1, 2, or 3 should ingest 35 kcal/kg body weight/day in order to maintain neutral nitrogen balance and to prevent catabolism of stored proteins for energy needs (Grade B, BEL 2). Patients with CKD and a GFR <25 mL/min should ingest 35 kcal/kg body weight/day if they are younger than age 60 years or 30 to 35 kcal/kg body weight/day if they are age 60 years or above (Grade B, BEL 2).

      3.Q6.3 Electrolytes

      • R27. All patients with CKD, regardless of CKD stage, should limit sodium intake to 2.0 g/day (Grade A, BEL 1). When potassium levels are elevated, potassium intake (including salt substitutes) should be limited to 2 to 3 g/day (Grade A, BEL 1). When diarrhea or vomiting is present, potassium intake should be liberalized and provided with meals that include a variety of fruits, vegetables, and grains (Grade D, BEL 4).
      • R28. Phosphate intake should be limited to 800 mg/day for patients with stage 3, 4, or 5 CKD (Grade A, BEL 1). All patients with CKD and hyperphosphatemia should get 2,000 mg/day of total calcium intake (binders plus calcium in meals) (Grade A, BEL 1).
      • R29. All patients with CKD who have hyperphosphatemia and secondary hyperparathyroidism should be treated with oral vitamin D to bring the total serum 25(OH)D level to greater than 30 ng/ mL (Grade A, BEL 1). If the intact parathyroid hormone (PTH) level remains elevated above treatment goal despite a serum 25(OH)D level higher than 30 ng/mL, treatment with an active form of vitamin D is indicated (Grade A, BEL 1).
      • R30. Patients with stage 3, 4, or 5 CKD should receive oral ferrous sulfate, 325 mg three times a day, in order to maintain transferrin saturation >20% and serum ferritin >100 ng/mL (Grade A, BEL 1)

      3.Q6.4 Renal Replacement Therapy

      • R31. For patients with end-stage kidney disease (ESKD) on RRT, potassium intake should be limited to 3 to 4 g/day (peritoneal dialysis) or 2 to 3 g/day (hemodialysis) (Grade A, BEL 1). Patients with DM and ESKD who are on RRT should be routinely queried regarding their eating habits, home glucose monitoring, and frequency and severity of hypoglycemia (Grade C, BEL 3).

      3.Q7 What Nutritional Recommendations are Appropriate for Bone Health?

      3.Q7.1 Calcium

      • R32. Total elemental calcium intake should be 1,000 mg/day for premenopausal women and men and 1,200 to 1,500 mg/day for postmenopausal women, preferentially from food sources (Grade A, BEL 1). Excessive amounts of elemental calcium intake, in the range of 2,000 mg/day, may increase the risk of kidney stones and other side effects and should therefore be actively discouraged (Grade A, BEL 1). A calcium intake greater than 1,500 mg/day is associated with an increased risk of advanced prostate cancer and should be discouraged (Grade B, BEL 2). Calcium supplements should be used if a patient’s meal plan does not provide adequate calcium intake (Grade A, BEL 1). Calcium citrate should be recommended instead of calcium carbonate for patients with achlorhydria, history of gastric surgery, and those being treated with proton-pump inhibitors or H2-receptor blockers (Grade B, BEL 2). For best absorption, calcium supplements should be limited to no more than 500 mg of elemental calcium per dose, since there is decreasing absorption with increasing doses (Grade A, BEL 1). A 24-hour urine calcium collection should be measured in patients with osteoporosis or patients at risk for bone loss in order to check calcium adequacy and test for hypercalciuria or malabsorption (Grade B, BEL 2).

      3.Q7.2 Vitamin D

      • R33. Serum 25(OH)D should be measured in individuals at risk for vitamin D deficiency (e.g., elderly, institutionalized, or malnourished patients) and in those with known osteopenia or osteoporosis (Grade A, BEL 1). Vitamin D should be supplemented to keep the plasma 25(OH)D level greater than 30 ng/mL (Grade A, BEL 1). For most patients, a daily intake of at least 1,000 to 2,000 IU of ergocalciferol (D2) or cholecalciferol (D3) should be adequate (Grade A, BEL 1). For patients with advanced renal failure in whom renal activation of vitamin D is impaired, calcitriol should be dosed to allow for adequate intestinal absorption of calcium (Grade A, BEL 1).

      3.Q8 What Nutritional Recommendations are

      Appropriate for Pregnancy and Lactation?

      3.Q8.1 Pregnancy Planning

      • R34. Prior to pregnancy, women should be encouraged to achieve a normal BMI (Grade A, BEL 1). Elevated fasting blood glucose prior to pregnancy should prompt screening for DM and initiation of a healthy eating meal plan and lifestyle modification (Grade A, BEL 1). Any chronic diseases, including DM, thyroid disorders, and rheumatologic disorders should be optimally controlled prior to conception with a focus on appropriate nutrition and physical activity (Grade D, BEL 4).

      3.Q8.2 Pregnancy

      • R35. The appropriate individual caloric intake should be calculated based on prepregnancy and current (pregnant) BMI (Grade D, BEL 4). Pregnant women who are vegetarian or vegan must be referred to a RD specializing in pregnancy to assist in meal planning and appropriate use of dietary supplements (Grade D, BEL 4). Women who are pregnant should consume 1.1 g/kg of protein per day in the second and third trimesters (Grade B, BEL 2). During pregnancy, less than 10% of calories should be derived from saturated fats and less than 10% should be derived from PUFAs, with the remainder from MUFAs (Grade D, BEL 4). Trans fatty acids should be avoided during a pregnancy since they may have adverse effects on fetal development (Grade B, BEL 2).
      • R36. Daily ingestion of a prenatal vitamin (PNV) is recommended for all women during pregnancy (Grade A, BEL 1). All women in their childbearing years should consume 400 μg/day of folic acid, and once pregnancy is confirmed, the intake should be adjusted to 600 μg/day (Grade B, BEL 2). Intake of vitamin A over 10,000 IU a day is teratogenic, so women should be advised against excessive supplementation (Grade B, BEL 2). All pregnant women should ingest a minimum of 250 μg of iodine daily (Grade B, BEL 2).
      • R37. Women who have DM and/or are insulin resistant should adjust the percentage of ingested carbohydrate during pregnancy to obtain proper glycemic control (Grade B, BEL 2). Women with gestational DM (GDM) should: (1) adhere to the recommendations for healthy eating for all pregnant women, (2) allow for appropriate weight gain during pregnancy (i.e., 2 to 5 pounds in the first trimester and 0.5 to 1 pound per week thereafter), (3) avoid concentrated sweets and “fast foods,” and (4) eat small, frequent meals with protein, having only one starch with breakfast and choosing high-fiber foods with lower fat content (Grade C, BEL 3)
      • R38. Patients should be instructed to consume less than 300 mg of caffeine (3 cups of coffee) per day during pregnancy, since caffeine can increase the incidence of miscarriage and stillbirth when consumed in larger quantities (Grade B, BEL 2).

      3.Q8.3 Lactation

      • R39. Whenever possible, exclusive breastfeeding is recommended for at least the first 6 months of life (Grade A, BEL 1). All women should be instructed on breastfeeding, made aware of community resources about breast feeding, and counseled to adjust their meal plans to meet nutritional needs during lactation (Grade A, BEL 1). All pregnant and lactating women should ingest a minimum of 250 μg of iodine daily (Grade B, BEL 2). During breastfeeding, basal insulin requirements decrease. Women who breastfeed should be advised to either lower their basal insulin dose (or basal insulin infusion rate if on an insulin pump) or eat a carbohydrate-containing snack prior to breastfeeding (Grade D, BEL 4).

      3.Q9 What Nutritional Recommendations are Appropriate for the Elderly?

      3.Q9.1 Healthy Eating for Energy Balance and Toward an Ideal Body Weight

      • R40. As people age, they should implement healthy eating to maintain an ideal body weight, since both overweight and underweight lead to increased morbidity and mortality (Grade A, BEL 1). In the elderly with sarcopenia and decreased basal metabolic rate, formulating a meal plan should include caloric reduction to maintain energy balance and to prevent fat-weight gain (Grade B, BEL 2). To constrain caloric overconsumption in the elderly while also ensuring micronutrient adequacy, quality foods low in calories and containing adequate amounts of HBV protein sources to provide EAAs and essential fatty acids (EFAs) and rich in micronutrients and fiber should be ingested routinely (Grade B, BEL 2). Quality food high in proteins, minerals, and vitamins but low in saturated fat, cholesterol, and trans fat (such as lean meat, fish, poultry, eggs, and dry beans and nuts) should be recommended for overweight or obese elderly patients to provide adequate protein intake without carrying a high risk for CVD (Grade A, BEL 1). Older adults should consume more of the nutrient-dense whole-grain foods, such as brown rice, whole-wheat breads, and whole-grain and fortified cereals to meet carbohydrate needs. Conversely, the consumption of refined starch-based foods such as processed potato, white bread, pasta, and other commercial products made of refined wheat flour should be limited to decrease the risk of obesity and DM (Grade B, BEL 2). Dehydration is a more prevalent condition in the elderly, and thirst sensation may be compromised with aging, therefore habitual fluid intake (about 2 quarts per day or eight 8-ounce glasses) is recommended (Grade B, BEL 2).
      • R41. On an individual basis, ingestion of nutrition supplements between meals should be recommended for undernourished elderly patients (Grade B, BEL 2). Energy and nutrient-dense foods, or manipulation of energy and nutrient density of the meal plan, should be recommended for the frail elderly to promote weight gain and improve clinical outcomes (Grade A, BEL 1). Food safety, including the prevention of food spoilage, should be provided for all elderly patients (Grade D, BEL 4).

      3.Q9.2 Healthy Eating to Prevent Micronutrient Deficiency in Older Adults

      • R42. To ensure adequacy of a wide variety of micronutrients, a daily mix of nutrient-dense foods, including fruits and vegetables, should be recommended (Grade B, BEL 2). In the elderly, pills should not be used as a substitute for meals (Grade D, BEL 4). The elderly should consume at least 3 daily servings of calcium-rich foods (Grade A, BEL 1). In the elderly, case finding for vitamin D and vitamin B12 deficiencies is reason able given their high prevalence with advancing age (Grade B, BEL 2). It is appropriate to recommend a daily multivitamin (MVI) to complement food intake in older adults who cannot achieve adequate micronutrient intake otherwise (Grade B, BEL 2). Surveillance to prevent toxicity from excess ingestion of vitamin pills is appropriate for the elderly (Grade C, BEL 3).

      3.Q9.3 Healthy Eating for the Frail Elderly

      • R43. Community nutrition assistance programs that provide individuals with home-delivered meals should be recommended for frail elderly patients still living independently (Grade A, BEL 1). Barriers to healthy eating in the elderly should be actively found and addressed, including provision of direct feeding assistance where self-feeding is not adequate, treatment of depression, group meals for institutionalized patients, correcting oral and dental problems leading to difficulties with eating, chewing or swallowing, addressing social isolation, rectifying polypharmacy, and treating underlying diseases (Grade B, BEL2). Physicians treating geriatric patients should make every effort to reduce the number of medications to achieve better medication adherence and to allow for better nutritional care (Grade D, BEL 4).
      You are what you eat ~ Victor Lindlahr

      4. APPENDIX: EVIDENCE BASE

      4.Q1 What are Healthy Eating and a Healthy Lifestyle?

      4.Q1.1 General Recommendations for Healthy Eating and Disease Prevention

      Healthy eating includes the adequate provision of macro- and micronutrients to sustain normal physiology and to avoid nutritional deficiencies. It also includes avoidance of excessive amounts of foods and beverages that may have a negative impact on health. Healthy eating must be maintained over a long time and should clearly be separated from fad diets, which are usually short lived and often unhealthy. Instead of applying the term “diet,” patients should be instructed on proper meal planning and the application of eating patterns (or meal patterns). The ability to read and understand nutrition fact labels should be an important component of patient nutrition education. These learned skills may be modified as needed and provide life-long durability.
      Similarly, the term “exercise” is stigmatized and can be an obstacle for most patients. The term “physical activity” should be used instead. Whereas it is extremely desirable to achieve CV fitness through regular, structured, continuous physical activity, this is not practical for most people most of the time. Two-thirds of patients are overweight or obese and may incur orthopedic or overuse injuries. Strenuous activity may also precipitate vascular events in people with unrecognized vascular disease. The simple concept that caloric expenditure is achieved by moving body mass over distance, or against gravity, translates into a myriad of opportunities when the focus is taken away from exercise. For example, a 2-minute walk every hour on the hour during the waking hours of the day achieves the same caloric expenditure as a 30-minute walk once (assuming the same velocity) (
      • Audelin M.C.
      • Savage P.D.
      • Toth M.J.
      • et al.
      Change of energy expenditure from physical activity is the most powerful determinant of improved insulin sensitivity in overweight patients with coronary artery disease participating in an intensive lifestyle modification program.
      [EL2, NRCT];
      • Garatachea N.
      • Torres Luque G.
      • Gonzalez Gallego J.
      Physical activity and energy expenditure measurements using accelerometers in older adults.
      [EL4, NE];
      • Koo B.K.
      • Han K.A.
      • Ahn H.J.
      • Jung J.Y.
      • Kim H.C.
      • Min K.W.
      The effects of total energy expenditure from all levels of physical activity vs. physical activity energy expenditure from moderate-to-vigorous activity on visceral fat and insulin sensitivity in obese Type 2 diabetic women.
      [EL1, RCT]).
      Healthy eating and physical activity must be accompanied by proper sleep (ideally 7 to 8 hours a night; less than 6 hours a day is associated with metabolic derangements and cognitive impairment) and adequate time for recreation and play and for stress reduction and happiness (
      • Nakata A.
      Investigating the associations between work hours, sleep status, and self-reported health among full-time employees.
      [EL3, SS];
      • Katano S.
      • Nakamura Y.
      • Nakamura A.
      • et al.
      Relationship between sleep duration and clustering of metabolic syndrome diagnostic components.
      [EL3, CCS]). The implementation of this knowledge into effective nutrition and regular physical activity by individual patients requires a team approach (
      • American Diabetes Association
      Position of the American Dietetic Association: integration of medical nutrition therapy and pharmacotherapy.
      [EL4, NE];
      • Wagner E.H.
      The role of patient care teams in chronic disease management.
      [EL4, NE]). It takes individualized care to achieve success.
      The United States Preventive Services Task Force recommends that individuals limit total and saturated dietary fat and cholesterol, maintain caloric balance, and increase fiber intake (
      • Moyer V.A.
      Behavioral counseling interventions to promote a healthful diet and physical activity for cardiovascular disease prevention in adults: U.S. Preventive Services Task Force recommendation statement.
      [EL2, MNRCT]). These guidelines are especially pertinent for our population’s health, as T2DM is becoming increasingly common, primarily due to an increase in the rising prevalence of obesity.
      The Finnish Diabetes Prevention study authors concluded that T2DM could be prevented by changes in the lifestyles of high-risk patients (
      • Tuomilehto J.
      • Lindström J.
      • Eriksson J.G.
      • et al.
      Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance.
      [EL1, RCT]). This study randomly assigned 522 middle-aged, overweight men and women (mean age, 55 years; mean BMI, 31 kg/m2) with impaired glucose tolerance to either an intervention or control group. The intervention group received counseling to reduce weight via nutritional intervention (lower fat intake, higher fiber intake) and increased daily physical activity. After 4 years, the cumulative incidence of DM defined by oral glucose tolerance testing (OGTT) was 11% in the intervention group and 23% in the control subjects.
      The Diabetes Prevention Program (DPP) randomized 3,234 adults (mean age, 51 years; mean BMI, 34 kg/m2) who had impaired fasting glucose and were at high risk for the development of T2DM into placebo, metformin, or lifestyle modification groups. The intensive lifestyle intervention was intended to help subjects lose and maintain a 7% weight loss through a healthy (low fat, reduced calorie) meal plan, 150 minutes of exercise per week, and 16 sessions of support and close follow-up in the first 6 months (
      • Knowler W.C.
      • Barrett-Connor E.
      • Fowler S.E.
      • et al.
      Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin.
      [EL1, RCT]). After an average follow-up of 2.8 years, lifestyle intervention resulted in more weight loss (5.6 kg) than either metformin (2.1 kg) or placebo (0.1 kg). The incidence of DM was reduced by 58% with lifestyle modification and by 31% with metformin, compared with placebo. The incidence of DM was 11.0, 7.8, and 4.8 cases per 100 person-years in the placebo, metformin, and lifestyle groups, respectively. Lifestyle modification was significantly more effective than metformin in preventing progression to DM.
      Healthy lifestyle also has beneficial effects on CV health. CV events were reduced by 35% and all-cause mortality by 40% over 6 years in a prospective cohort study of 15,708 middle-aged adults (ages 45 to 64 years) who adopted four healthy lifestyle habits to include no tobacco smoking, regular physical activity (at least walking) 150 minutes or more per week, maintaining a normal BMI <25 kg/m2, and eating at least five fruits and vegetables daily (
      • King D.E.
      • Mainous 3rd, A.G.
      • Geesey M.E.
      Turning back the clock: adopting a healthy lifestyle in middle age.
      [EL2, PCS]).
      The most common cancers in the United States are breast, lung, and colorectal cancer in women and prostate, lung, and colorectal cancer in men. The American Cancer Society (ACS) recommends eating at least 5 servings of fruits and vegetables daily (

      American Cancer Society. Fruits and Vegetables: Do You Get Enough? Available at: http://www.cancer.org/healthy/eathealthygetactive/eathealthy/fruits-and-vegetables-do-you-get-enough. [EL4, NE]

      [EL4, NE]). Fruits, vegetables, and whole-grain foods contain vitamins and antioxidants that may lower the risk of lung and gastrointestinal (esophagus, stomach, colon) cancers (Table 5).
      Table 5Natural Compounds in Food Important in Maintaining Health
      Greater nutrition
      • Whole foods contain a variety of compounds important to health. As an example, an orange provides vitamin C, beta carotene, calcium, and other nutrients, whereas a vitamin C supplement does not.
      • o
        Fortified foods: means that 1 or more nutrients have been added that were originally absent from the food.
      • o
        Enriched foods: means that nutrients lost during the preparation of foods for consumption have been added back to the food.
      Essential fiber
      • Fiber is important in digestion and may play a role in disease prevention.
      • o
        Soluble fiber sources: beans, fruits, and vegetables and some grains.
      • o
        Insoluble fiber sources: whole grains and some fruits and vegetables.
      Phytochemicals/Flavonoids
      • A nonnutrient compound synthesized by plants. Flavonoid is a common name for a phytochemical that may function as an antioxidant.
      • o
        May play a role in the prevention of disease by enhancing protective enzymes in the body, detoxifying carcinogens in foods, and preventing cell damage that can lead to cancer.
      • o
        Found in many plant foods, including whole grains, legumes, nuts, fruits (berries) and cruciferous vegetables (broccoli, cabbage, cauliflower, Brussels sprouts, etc.).
      Antioxidants
      • A compound that can protect the body against free radicals, which are unstable molecules that can form anywhere in the body leading to cell damage and have been linked to both cardiovascular disease and cancer.
      • o
        Examples of antioxidants include lycopene, beta-carotene, carotenoids, and vitamins A, C, and E.
      • o
        Foods (containing antioxidants): tomatoes (lycopene), berries to include strawberries/blueberries/ blackberries/raspberries/cranberries (vitamin C, ellagic acid, anthocyanin), carrots (beta-carotene), spinach (carotenoids, lutein, and zeaxanthin) and other dark leafy vegetables, whole grains (ligans, saponins) to include breads, flax, and sesame seeds.
      Unfortunately, few individuals meet national recommendations for healthy eating. In an evaluation of healthy eating habits of more than 153,000 individuals using the Behavioral Risk Factor Surveillance System (BRFSS) in 2000, only 23% reported consuming at least five fruits and vegetable servings daily (
      • Reeves M.J.
      • Rafferty A.P.
      Healthy lifestyle characteristics among adults in the United States, 2000.
      [EL3, SS]). A similar finding was reported in Olmsted County, Minnesota, where only 16% of 732 individuals reported meeting standard nutrition recommendations for consuming both five or more servings of fruits and/or vegetables per day, and no more than 30% of calories from fat (
      • DeBoer S.W.
      • Thomas R.J.
      • Brekke M.J.
      • et al.
      Dietary intake of fruits, vegetables, and fat in Olmsted County.
      [EL3, SS]).
      Early nutrition guidelines have been based on treatment of clinical nutrient deficiencies. Prospective epidemiologic studies and randomized trials of nutrition and nutrient supplements have advanced our understanding of the contribution of nutrition to health maintenance and disease prevention and treatment. Growing evidence suggests that fruit and vegetable consumption is inversely related to the risk of coronary heart disease (CHD) and stroke (
      • Joshipura K.J.
      • Hu F.B.
      • Manson J.E.
      • et al.
      The effect of fruit and vegetable intake on risk for coronary heart disease.
      [EL2, PCS];
      • Bazzano L.A.
      • He J.
      • Ogden L.G.
      • et al.
      Legume consumption and risk of coronary heart disease in US men and women: NHANES I Epidemiologic Follow-up Study.
      [EL2, PCS]). Observational studies have consistently shown that meal plans high in antioxidant vitamins from ingestion of fruits and vegetables are associated with a lower risk of CVD (
      • Jha P.
      • Flather M.
      • Lonn E.
      • Farkouh M.
      • Yusuf S.
      The antioxidant vitamins and cardiovascular disease. A critical review of epidemiologic and clinical trial data.
      [EL4, NE]). A review and meta-analysis of prospective cohort data concluded that intake of fruits and vegetables at the 90th percentile reduced the risk of CHD by a median of 15% compared with the 10th per-centile of consumption (
      • Law M.R.
      • Morris J.K.
      By how much does fruit and vegetable consumption reduce the risk of ischaemic heart disease?.
      [EL2, MNRCT]). A meta-analysis of cohort studies also found that a higher intake of fruits and vegetables is associated with a lower risk of stroke. The risk was reduced with only 3 to 5 servings of fruits and vegetables daily, with further stroke risk reduction if more than 5 servings were consumed daily (relative risk [RR], 0.89 and 0.74, respectively) (
      • He F.J.
      • Nowson C.A.
      • MacGregor G.A.
      Fruit and vegetable consumption and stroke: meta-analysis of cohort studies.
      [EL2, MNRCT]). One study found the lowest risk of stroke was associated with a high consumption of cruciferous vegetables (e.g., broccoli, cabbage, cauliflower, Brussels sprouts), green leafy vegetables, citrus fruits, and vitamin C-rich fruits and vegetables (
      • Joshipura K.J.
      • Hu F.B.
      • Manson J.E.
      • et al.
      The effect of fruit and vegetable intake on risk for coronary heart disease.
      [EL2, PCS]). A meta-analysis of 9 cohort studies including 221,080 men and women found that fruit and vegetable intake was inversely related to CHD. There was a 4% decline in CHD for each daily portion of additional fruit and vegetable consumed and a 7% decline for fruit intake (
      • Dauchet L.
      • Amouyel P.
      • Hercberg S.
      • Dallongeville J.
      Fruit and vegetable consumption and risk of coronary heart disease: a meta-analysis of cohort studies.
      [EL2, MNRCT]). Thus, daily ingestion of at least 8 servings of fresh fruits and vegetables should be recommended for everyone.
      Natural compounds found in food may work individually or in combination and confer health benefits beyond those of dietary supplements and nutraceuticals (Table 5) (
      • Mechanick J.I.
      • Brett E.M.
      • Chausmer A.B.
      • Dickey R.A.
      • Wallach S.
      • American Association of Clinical Endocrinologists
      American Association of Clinical Endocrinologists medical guidelines for the clinical use of dietary supplements and nutraceuticals.
      [EL4, NE]). A large number of potentially anticarcinogenic and antioxidant agents are found in fish, fruits, vegetables, fiber, and plant compounds (e.g., flavonoids, phenols, protease inhibitors, sterols, allium compounds, and limonene) (
      • Steinmetz K.A.
      • Potter J.D.
      Vegetables, fruit, and cancer. II. Mechanisms.
      [EL4, NE]). The antioxidant vitamins include vitamins E, C, and A (to include carotenoids such as beta-carotene). A number of studies have examined the hypothesis that antioxidants may prevent cancer and CVD by augmenting the body’s ability to dispose of toxic free radicals, thereby limiting oxidative damage (
      • Diaz M.N.
      • Frei B.
      • Vita J.A.
      • Keaney Jr., J.F.
      Antioxidants and atherosclerotic heart disease.
      [EL4, NE]). Retrospective and small prospective studies have suggested a direct relationship between fruit and vegetable intake and the prevention of cancers (
      • Steinmetz K.A.
      • Potter J.D.
      Vegetables, fruit, and cancer.
      [EL2, MNRCT];
      • Genkinger J.M.
      • Platz E.A.
      • Hoffman S.C.
      • Comstock G.W.
      • Helzlsouer K.J.
      Fruit, vegetable, and antioxidant intake and all-cause, cancer, and cardiovascular disease mortality in a community-dwelling population in Washington County.
      [EL2, PCS]). However, caution must be used in interpreting these studies, as the outcomes noted may be due to effects of the antioxidants themselves, other food-related compounds, or the possibility that people who consume healthier meals (e.g., more fruit and vegetables and less fat) live healthier lives.
      The relationship between fiber intake and colorectal cancer risk is unclear. Large observational studies have reported that high fiber intake reduces the risk of colorectal adenomas (
      • Peters U.
      • Sinha R.
      • Chatterjee N.
      • et al.
      Dietary fibre and colorectal adenoma in a colorectal cancer early detection programme.
      [EL2, RCCS]) and cancer (
      • Bingham S.A.
      • Day N.E.
      • Luben R.
      • et al.
      Dietary fibre in food and protection against colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC): an observational study.
      [EL1, RCT]). In contrast, no relationship was noted between a high-fiber meal plan and the recurrence rate of colorectal adenomas in the large observational Nurses’ Health Study (
      • Fuchs C.S.
      • Giovannucci E.L.
      • Colditz G.A.
      • et al.
      Dietary fiber and the risk of colorectal cancer and adenoma in women.
      [EL2, PCS]) or in a randomized secondary prevention trial (
      • Schatzkin A.
      • Lanza E.
      • Corle D.
      • et al.
      Lack of effect of a low-fat, high-fiber diet on the recurrence of colorectal adenomas. Polyp Prevention Trial Study Group.
      [EL1, RCT]). A systematic review of 5 studies involving 4,349 patients followed for 2 to 4 years found no definitive evidence that increased dietary fiber reduced the incidence or recurrence of adenomatous colorectal polyps (
      • Asano T.
      • McLeod R.S.
      Dietary fibre for the prevention of colorectal adenomas and carcinomas.
      [EL1, MRCT]). There is no apparent reason for the conflicting results seen in these large observational studies. Of note, a pooled analysis of 13 prospective cohort studies involving 725,628 men and women followed for 6 to 20 years found that fiber intake was inversely associated with the risk of colorectal cancer, but the association was no longer apparent after accounting for other nutritional risk factors (
      • Park Y.
      • Hunter D.J.
      • Spiegelman D.
      • et al.
      Dietary fiber intake and risk of colorectal cancer: a pooled analysis of prospective cohort studies.
      [EL2, MNRCT]). Thus, increasing fiber intake should not be recommended to lower the risk of colorectal neoplasia.
      The strongest evidence for beneficial health effects of a plant-based meal plan comes from mortality studies and the Mediterranean dietary pattern. A study of older Americans (American Association of Retired Persons cohort) was scored for adherence to the Mediterranean dietary pattern according to higher intake of foods considered to be healthy (vegetables, fruits, nuts, legumes, grains, fish, and monounsaturated fats) and for lower intakes for those foods considered to be unhealthy (high-fat dairy products, meat, and saturated fats). Mortality was reduced among individuals who adhered to the healthier Mediterranean dietary pattern. During 5 years of follow-up, a 20% reduction in total mortality and CV and cancer mortality was seen in men. Similar reductions in total mortality but smaller benefits for cancer mortality were seen in women (
      • Mitrou P.N.
      • Kipnis V.
      • Thiébaut A.C.
      • et al.
      Mediterranean dietary pattern and prediction of all-cause mortality in a US population: results from the NIH-AARP Diet and Health Study.
      [EL2, PCS]). The Lyon Diet Heart Study assessed dietary changes to include 20% increases in consumption of vitamin C-rich fruits and bread, decreases in processed and red meat, and use of a margarine based on rapeseed (canola) oil. This meal plan led to a 70% reduction in all-cause mortality (
      • Leaf A.
      Dietary prevention of coronary heart disease: the Lyon Diet Heart Study.
      [EL4, NE];
      • de Lorgeril M.
      • Salen P.
      • Martin J.L.
      • Monjaud I.
      • Delaye J.
      • Mamelle N.
      Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction: final report of the Lyon Diet Heart Study.
      [EL1, RCT]). A meta-analysis of 12 studies involving 8 cohorts found that individuals strictly adhering to the Mediterranean diet had a reduced risk of dying from cancer and CVD, reporting 6, 9, and 9% reductions in cancer, CVD, and overall mortality, respectively (
      • Sof F.
      • Cesari F.
      • Abbate R.
      • Gensini G.F.
      • Casini A.
      Adherence to Mediterranean diet and health status: meta-analysis.
      [EL2, MNRCT]). The Mediterranean dietary pattern has also been shown to provide protection against T2DM (
      • Martínez-González M.A.
      • de la Fuente-Arrillaga C.
      • Nunez-Cordoba J.M.
      • et al.
      Adherence to Mediterranean diet and risk of developing diabetes: prospective cohort study.
      [EL2, PCS]). In a study of graduates from the University of Navarra, in Spain, 13,000 subjects with no prior history of DM were followed a median of 4.4 years for dietary habits and overall health. Researchers found that persons who adhered closely to the Mediterranean dietary pattern had an 83% reduction in the RR of developing DM. The European Prospective Investigation into Cancer and Nutrition study followed 23,000 Greek men and women for 8.5 years to assess the Mediterranean diet and mortality. The authors reported that consuming a diet high in vegetables and low in meat and meat products was more significantly associated with lower mortality than was eating cereal and fish. Moderate alcohol intake and increased fruit, nut, and legume consumption were also associated with a lower mortality risk in this study (
      • Trichopoulou A.
      • Bamia C.
      • Trichopoulos D.
      Anatomy of health effects of Mediterranean diet: Greek EPIC prospective cohort study.
      [EL2, PCS]).
      There is strength in the world literature to claim that healthy eating, especially the Mediterranean dietary pattern, contributes significantly to human health maintenance and disease prevention. It is worth noting that healthy eating requires a healthy food supply, and implicit in this is the role of government and public health organizations.

      4.Q1.2 Healthy Macronutrient Intake

      Studies have shown that one macronutrient profile may not be appropriate for all individuals irrespective of their CVD risk status. The Optimal Macronutrient Intake Trial to Prevent Heart Disease (Omni-Heart) compared meal plans that emphasized the three different macronutrients in isocaloric trial groups: complex carbohydrates (CARB meal plan) similar to the DASH meal plan (58% carbohydrate, 15% protein, 27% fat), protein (PROT) meal plan, of which half was from plant sources (48% carbohydrate, 25% protein, 27% fat), and fat (UNSAT meal plan) meal plan, of which unsaturated fats, such as olive oil, canola oil, and nuts and seeds were emphasized (48% carbohydrate, 15% protein, 37% fat) (
      • Appel L.J.
      • Sacks F.M.
      • Carey V.J.
      • et al.
      Effects of protein, monounsaturated fat, and carbohydrate intake on blood pressure and serum lipids: results of the OmniHeart randomized trial.
      [EL1, RCT]). Participants (n = 164) were generally healthy with prehypertension or stage 1 hypertension with uncontrolled but relatively normal blood lipid levels (i.e., baseline LDL-C was 129.2 mg/L). All results were compared to the BP and lipid levels obtained after the CARB meal plan. After 6 weeks of controlled feeding, the PROT meal plan lowered systolic BP (SBP) and diastolic BP (DBP) by 1.4 and 3.5 mm Hg, respectively, and the UNSAT meal plan lowered SBP and DBP by 1.3 and 2.9 mm Hg, respectively, in those with hypertension. The PROT meal plan lowered LDL-C by 3.3 mg/dL, high-density-lipoprotein cholesterol (HDL-C) by 1.3 mg/dL, and triglycerides (TGs) by 15.7 mg/dL, while the UNSAT meal plan increased HDL-C by 1.1 mg/dL, lowered TG by 9.6 mg/dL, and did not have an effect on LDL-C. In sum, the DASH-type meal plan decreases CVD risk by 16.1% according to the Framingham risk equation; however, substituting ~10% of total calories from carbohydrate with either protein or unsaturated fat further decreases CVD risk (PROT, -21.0%; UNSAT, -19.6%) by improving both BP and lipid values.
      The macronutrient profile of meals has remarkably diverse effects on different CVD risk factors. The recommended meal plan should complement personal tastes of individuals within the guidelines for calories and macronutrient distributions. Both macronutrient distribution and quality of macronutrients (i.e., sugar versus starch or fiber, saturated versus unsaturated fats, etc.) are important in improving CVD risk factors and outcomes.

       Carbohydrates and Fiber

      Healthy carbohydrates are high in fiber (both soluble and insoluble), sterols, and stanols, low in energy density, and contain bioavailable micronutrients. Viscous or soluble fiber, specifically beta-glucan or pectin, decreases total cholesterol (TC) by numerous mechanisms, including increasing bile acid secretion and decreasing endogenous cholesterol production (
      • Schneeman B.O.
      Gastrointestinal physiology and functions.
      [EL4, NE]). Insoluble fiber, often thought of as the “roughage” in vegetables or the hull of a grain, creates a bulky stool, allowing the food to pass through the intestine more quickly, which decreases absorption of calories and nutrients. In addition, fiber may delay gastric emptying, which affects satiety and absorption of carbohydrates (
      • Schneeman B.O.
      Gastrointestinal physiology and functions.
      [EL4, NE]). Sterols and stanols are cholesterol derivatives from plants that block the absorption of cholesterol in the intestine and increase bile production, both of which decrease serum cholesterol (
      • Patel S.B.
      Plant sterols and stanols: their role in health and disease.
      [EL4, NE]).
      Complex carbohydrates are naturally high in fiber and simple carbohydrates generally are not. For those “counting carbs,” the grams of fiber and sugar alcohols must be subtracted from total grams of carbohydrates, resulting in the gram amount of available carbohydrates in the product. Therefore, it is possible to eat a plant-based meal that is low in carbohydrate (sugars and starches) due to the high fiber content of fruits, vegetables, and whole grains (
      • Otten J.J.
      • Hellwig J.P.
      • Meyers L.D.
      Dietary reference intakes (DRI). The essential guide to nutrient requirements.
      [EL4, NE]).

       Fruits and Vegetables

      Fruit and vegetable intake should be ≥4.5 cups (
      • Lloyd-Jones D.M.
      • Hong Y.
      • Labarthe D.
      • et al.
      Defining and setting national goals for cardiovascular health promotion and disease reduction: the American Heart Association’s strategic Impact Goal through 2020 and beyond.
      [EL4, NE]). Adults should have 2.5 to 3 cups of vegetables and 1.5 to 2 cups of fruit daily in a 2,000 calorie meal plan, for health promotion and prevention of chronic disease (
      • U.S. Department of Agriculture
      Dietary Guidelines for Americans.
      [EL4, NE]). These recommendations are similar to the 4 to 5 servings of fruit and 4 to 5 servings of vegetables recommended by TLC and DASH meal plans (1 serving = 0.5 cup of cooked vegetables) (Table 6). Frozen, canned, dried, and fresh options allow for flexibility in the meal plan and help with the cost of buying fresh produce.
      Table 6Examples of Meal Patterns Consistent with AHA Nutrition Guidelines
      Food groupTLCDASHMediterraneanExamples of Servings
      Vegetables4-5 servings/day5 servings/dayEat daily1 c raw leafy vegetables, 1/2 c cut-up raw or cooked vegetables, 1/2 c vegetable juice
      Fruits4-5 servings/day4 servings/dayEat daily1 med. fruit, 1/4 c dried fruit, 1/2 c fresh, frozen canned fruit, 1/2 c fruit juice
      Grains6-8 servings/day7 servings/dayEat daily1 slice bread, 1 oz. dry cereal, 1/2 c cooked rice or pasta
      Fat-free or low-fat milk products2-3 servings/day2-3 servings/dayEat daily (Specifically, cheese and yogurt in low to moderate amounts)1 c milk, 1 c yogurt, 1/5 oz. cheese
      Lean meats, poultry, fish<6 oz. per day5 oz. per dayEat fish and poultry twice weekly ≤7 eggs /week1 oz. cooked Serve – 3 oz. cooked
      Nuts, seeds, legumes, pulses4-5 servings/dayCounted in vegetable servingsEat daily1/3 c, 2 TBSP peanut butter or seeds, 1/2 c dry beans or peas
      Fats and oils2-3 servings/dayAmount depends on daily calorie levelUse olive oil daily in cooking1 tsp. soft margarine, 1 TBSP mayonnaise, 1 tsp. vegetable oil, 2 TBSP salad dressing
      Sweets and added sugars5 servings/ weekNo recommendation2 sweets/week1 TBSP sugar, jelly or jam; 1/2 c sorbet, 1 c lemonade
      Abbreviations: AHA = American Heart Association; c = cup; DASH = Dietary Approaches to Stop Hypertension; oz. = ounce; TBSP = tablespoon; TLC = therapeutic lifestyle changes; tsp. = teaspoon.
      Mediterranean dietary pattern adapted with permission from Oldways Mediterranean Pyramid (Copyright of Oldways Preservation and Exchange Trust; Accessed at: http://www.oldwayspt.org).
      Adapted with permission from: Lichtenstein AH, et al. Diet and lifestyle recommendations, revision 2006: A scientific statement from the American Heart Association Nutrition Committee. Circulation. 2006;114:82-96.
      Fruits and vegetables are an excellent source of total fiber intake but are diverse in their fiber composition (i.e., insoluble or soluble [viscous]) (
      • De Moura F.F.
      • Lewis K.D.
      • Falk M.C.
      Applying the FDA definition of whole grains to the evidence for cardiovascular disease health claims.
      [EL2, MNRCT]). The concentration of plant sterol and stanol esters in fruits and vegetables is relatively low; therefore, to attain effective levels of sterols and stanols, foods with concentrated amounts of these compounds, such as fortified margarines, juices, yogurts, milk, salad dressings, and snack bars, are recommended (
      • National Cholesterol Education Program; National Heart, Lung, and Blood Institue; National Institutes of Health
      Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report.
      [EL4, NE]). Fruits and vegetables are naturally low in sodium and high in potassium, which contribute to the decreases in BP (
      • Appel L.J.
      • Brands M.W.
      • Daniels S.R.
      • et al.
      Dietary approaches to prevent and treat hypertension: a scientific statement from the American Heart Association.
      [EL4, NE]). An observational study showed that increasing fruit and vegetable intake by 1 serving per day was associated with a 4% decreased risk of CHD (
      • Joshipura K.J.
      • Hu F.B.
      • Manson J.E.
      • et al.
      The effect of fruit and vegetable intake on risk for coronary heart disease.
      [EL2, PCS]). The evidence from randomized controlled trials (RCTs) on CVD endpoints is less clear (
      • Dauchet L.
      • Amouyel P.
      • Dallongeville J.
      Fruits, vegetables and coronary heart disease.
      [EL4, NE]).

       Whole Grains

      High-fiber whole grain (≥1.1 gram of fiber per 10 g of carbohydrate) intake should be more than three 1-ounce equivalent servings per day (
      • Lloyd-Jones D.M.
      • Hong Y.
      • Labarthe D.
      • et al.
      Defining and setting national goals for cardiovascular health promotion and disease reduction: the American Heart Association’s strategic Impact Goal through 2020 and beyond.
      [EL4, NE]). Current recommendations by the United States Department of Agriculture (USDA) for servings of grains are 5 to 8 ounces of grains per day for adults on a 2,000 calorie meal plan, with at least half from whole grain sources (
      • U.S. Department of Agriculture
      Dietary Guidelines for Americans.
      [EL4, NE]). The DASH and TLC meal plans recommend similar amounts of grain per day but emphasize only whole grains.
      Many epidemiological studies have reported that higher intakes of whole grains are associated with a lower BMI, percent fat mass, waist circumference, and CVD risk (
      • McKeown N.M.
      • Yoshida M.
      • Shea M.K.
      • et al.
      Whole-grain intake and cereal fiber are associated with lower abdominal adiposity in older adults.
      [EL2, NRCT];
      • Good C.K.
      • Holschuh N.
      • Albertson A.M.
      • Eldridge A.L.
      Whole grain consumption and body mass index in adult women: an analysis of NHANES 1999-2000 and the USDA pyramid servings database.
      [EL3, SS];
      • Mellen P.B.
      • Walsh T.F.
      • Herrington D.M.
      Whole grain intake and cardiovascular disease: a meta-analysis.
      [EL2, MNRCT]). Increased intake of cereal fiber specifically is associated with lower body weight and waist circumference over time (
      • Du H.
      • van der A D.L.
      • Boshuizen H.C.
      • et al.
      Dietary fiber and subsequent changes in body weight and waist circumference in European men and women.
      [EL2, PCS]). However, RCTs have not demonstrated that eating whole grains improves weight loss outcomes (
      • Katcher H.I.
      • Legro R.S.
      • Kunselman A.R.
      • et al.
      The effects of a whole grain-enriched hypocaloric diet on cardiovascular disease risk factors in men and women with metabolic syndrome.
      [EL1, RCT]). Whole grains, such as oats, whole wheat, barley, rye, and brown and wild rice vary in their fiber and phytochemical content (
      • De Moura F.F.
      • Lewis K.D.
      • Falk M.C.
      Applying the FDA definition of whole grains to the evidence for cardiovascular disease health claims.
      [EL2, MNRCT]). For example, the soluble fiber content is high in oats and barley, while insoluble fiber is found in the bran of whole wheat. Knowing the different nutritional profiles of whole grains is important with regards to health claims. For example, 3 grams of beta-glucan soluble fiber per day from oats and barley or 7 grams per day of soluble fiber from psyllium reduces risk for CVD by lowering LDL-C (
      • De Moura F.F.
      • Lewis K.D.
      • Falk M.C.
      Applying the FDA definition of whole grains to the evidence for cardiovascular disease health claims.
      [EL2, MNRCT];

      21 Code of Federal Regulations 10.181. Health claims: Soluble Fiber from Certain Foods and Risk of Coronary Heart Disease (CHD). Washington, DC: U.S. Government Printing Office. [EL4, NE]

      [EL4, NE]).
      A meta-analysis of 20 studies showed that increasing fiber to ~14 g/day decreased SBP by 1.6 mm Hg and DBP by 2.0 mm Hg (
      • He J.
      • Whelton P.K.
      Effect of dietary fiber and protein intake on blood pressure: a review of epidemiologic evidence.
      [EL2, MNRCT]). A prospective cohort study demonstrated that those with the highest intake of whole grain per day were 19% less likely to develop hypertension (RR, 0.81; P<.0001) than those who ate the least amount of whole grains per day (
      • Flint A.J.
      • Hu F.B.
      • Glynn R.J.
      • et al.
      Whole grains and incident hypertension in men.
      [EL2, PCS]). Inclusion of whole grains in place of refined grains will add fiber and micronutrients to meals that aid in BP lowering. However, whole grains are not fortified with micronutrients like refined grains, thus the availability of some micronutrients typically is less. The food industry has increased the amount of whole grain products available, which facilitates meeting the whole-grain intake recommendation.

       Reduced-Fat Dairy: Milk and Yogurt

      Yogurt and milk are composed primarily of carbohydrates but also are a good source of high-quality protein. The USDA recommends 3 cups of reduced-fat dairy per day for all age groups, although the dairy product must contain a high amount of calcium to be included (
      • U.S. Department of Agriculture
      Dietary Guidelines for Americans.
      [EL4, NE]). The DASH and TLC meal plans align with the USDA recommendations. However, the Mediterranean meal plan focuses mainly on cheese and yogurt as dairy sources (reduced-fat cheese, discussed in the “Animal Protein” section). Full-fat dairy products such as whole milk and full-fat yogurt contribute significant amounts of saturated fat to meals, which can increase serum LDL-C. However, saturated fat from milk may increase only the number of larger, less atherogenic LDL-C particles (
      • Sjogren P.
      • Rosell M.
      • Skoglund-Andersson C.
      • et al.
      Milk-derived fatty acids are associated with a more favorable LDL particle size distribution in healthy men.
      [EL3, CSS]). Regardless, consuming reduced-fat milk and yogurt will not adversely affect the lipid profile, as the saturated fat has been decreased or removed. Of note, reduced-fat yogurts sometimes have added sugars as a substitute for fat and may not be lower in calories than the full-fat option; it is important to compare labels to determine whether the reduced-fat formulation is healthier.
      Reduced-fat milk, low-fat cottage cheese, and yogurt are low-calorie sources of highly bioavailable micronutrients, such as calcium, potassium, and magnesium, which are associated with lower BP. Increasing the number of daily servings of reduced-fat milk and yogurt (3.4 servings/day vs. 0.4 servings/day) in a meal plan high in fruits and vegetables favorably alters the intracellular micronutrient content (i.e., decreases calcium and increases magnesium), which is shown to affect an individual’s BP response to a dairy-rich meal plan (
      • Hilpert K.F.
      • West S.G.
      • Bagshaw D.M.
      • et al.
      Effects of dairy products on intracellular calcium and blood pressure in adults with essential hypertension.
      [EL1, RCT]). The DASH dietary pattern lowers SBP by 5.0 mm Hg and DBP by 3.0 mm Hg more than a control meal plan. Fifty percent of the reduction in BP is ascribed to reduced-fat dairy intake (
      • Appel L.J.
      • Moore T.J.
      • Obarzanek E.
      • et al.
      A clinical trial of the effects of dietary patterns on blood pressure. DASH Collaborative Research Group.
      [EL1, RCT]). In addition to the effects of micronutrients, fermented dairy peptides (2.5 to 5.6 mg/day) also decrease SBP by 4.8 mm Hg and DBP by 2.2 mm Hg over 4 weeks (
      • Xu J.Y.
      • Qin L.Q.
      • Wang P.Y.
      • Li W.
      • Chang C.
      Effect of milk tripeptides on blood pressure: a meta-analysis of randomized controlled trials.
      [EL1, MRCT]). Replacing high-fat dairy products with lower fat versions has beneficial effects on BP and lowers TC and LDL-C.

       Protein Sources

      Higher intake of protein (24% vs. 14.7% of total calories), from either plant or animal sources, is associated with a reduced risk of CVD events (RR, 0.75; 95% confidence interval [CI], 0.61-0.92), specifically ischemic heart disease in women (
      • Hu F.B.
      • Stampfer M.J.
      • Manson J.E.
      • et al.
      Dietary saturated fats and their food sources in relation to the risk of coronary heart disease in women.
      [EL2, PCS]). Manipulating protein intake at the expense of carbohydrate or fat can lower CVD risk. Replacing 10% of calories from carbohydrates in the DASH meal plan with protein from both plant and animal sources (25% of total calories) resulted in lower LDL-C, TG, and HDL-C, as well as lowered SBP when compared to the unmodified DASH meal plan (
      • Appel L.J.
      • Sacks F.M.
      • Carey V.J.
      • et al.
      Effects of protein, monounsaturated fat, and carbohydrate intake on blood pressure and serum lipids: results of the OmniHeart randomized trial.
      [EL1, RCT]).
      The Food Guide Pyramid recommended 5.5 to 6 ounces of protein food sources per day for adults eating a 2,000 calorie meal plan and emphasizes variety for health benefits (
      • U.S. Department of Agriculture
      Dietary Guidelines for Americans.
      [EL4, NE]). More recently, the FDA has introduced My Plate as a nutrition aid, calling for one-fourth of a medium sized plate to be a source of protein (
      • U.S. Department of Agriculture
      Dietary Guidelines for Americans.
      [EL4, NE]). The TLC and DASH meal plans recommend <6 ounces or ≤5 ounces per day of lean meats, respectively. The Mediterranean Diet Pyramid specifies increased plant compared to animal protein, and recommends daily servings of beans, legumes, and nuts and weekly servings of poultry and fish (Table 6). The Acceptable Macronutrient Distribution Range for protein is 10 to 35% of total calories to prevent chronic disease (
      • Otten J.J.
      • Hellwig J.P.
      • Meyers L.D.
      Dietary reference intakes (DRI). The essential guide to nutrient requirements.
      [EL4, NE]).

       Animal Protein Sources: Lean Meat Cuts, Skinless Poultry, Lean Fish, Reduced-Fat Cheese

      Animal sources of protein can be sources of saturated fat and cholesterol as well. Reduced-fat animal protein sources are recommended. Lean meat cuts, reduced-fat cheese, egg whites, fish, and skinless poultry are all heart-healthy animal protein options. In the PREMIER trial, a free-living study assessing weight loss strategies, 66% of the protein consumed was animal protein, namely poultry, dairy, and beef (
      • Lin P.H.
      • Miwa S.
      • Li Y.J.
      • Wang Y.
      • Levy E.
      • Lastor K.
      • Champagne C.
      Factors influencing dietary protein sources in the PREMIER trial population.
      [EL1, RCT]). Both lean red meat and white meat have been shown to be equally efficacious in improving lipid profiles in hypercholesterolemic participants when incorporated into the TLC meal plan. When lean red or white meat makes up 80% of protein intake for 36 weeks, this lowers LDL-C by 1 to 3%, raises HDL-C by 2%, and TGs are unchanged (
      • Davidson M.H.
      • Hunninghake D.
      • Maki K.C.
      • Kwiterovich Jr., P.O.
      • Kafonek S.
      Comparison of the effects of lean red meat vs lean white meat on serum lipid levels among free-living persons with hypercholesterolemia: a long-term, randomized clinical trial.
      [EL1, RCT]). Intake of lean white fish (low in omega-3 fatty acids) lowers BP as compared to lean meat or fatty fish (high in omega-3 fatty acids) in a population at high risk for CVD. While omega-3 fatty acids have a slight antihypertensive effect at higher doses (see “Omega-3 Fatty Acids” section), one study reported that fish proteins had angiotensin-converting enzyme inhibitor (ACEI) effects (
      • Erkkilä A.T.
      • Schwab U.S.
      • de Mello V.D.
      • et al.
      Effects of fatty and lean fish intake on blood pressure in subjects with coronary heart disease using multiple medications.
      [EL1, RCT]).
      Cheeses that are lower in fat content include part-skim mozzarella, some goat cheeses, string cheese, and some soft cheeses, due to their high water content. Many common cheeses are available as reduced- or no-fat versions, such as mozzarella, cheddar, Monterey Jack, brie, Swiss, and Muenster. Cheese intake often has been a proxy for meal plans that are high in saturated fat and of lower quality dietary patterns; however, the type of cheese reportedly eaten may mediate the associations between cheese intake and CVD risk factors (
      • Panagiotakos D.
      • Pitsavos C.
      • Chrysohoou C.
      • et al.
      Dietary patterns and 5-year incidence of cardiovascular disease: a multivariate analysis of the ATTICA study.
      [EL2, PCS]). For example, compared to those who eat cheese less frequently (zero servings per month), men who eat cheese more frequently (15 to 30 times per month) have worse lipid and BP profiles. On the other hand, women who eat cheese less frequently have slightly improved lipid profiles compared to those who eat cheese more frequently (
      • Houston D.K.
      • Driver K.E.
      • Bush A.J.
      • Kritchevsky S.B.
      The association between cheese consumption and cardiovascular risk factors among adults.
      [EL2, CSS]). The type of cheese and processing determines saturated fat and sodium levels. However, all cheese contains bioactive compounds such as calcium, conjugated linoleic acid, and dairy peptides. Fermentation of dairy peptides by bacteria in the gut or in the processing procedure produces other bioactive compounds that improve CVD risk profiles by lowering BP, improving lipids, and decreasing inflammation (
      • Ebringer L.
      • Ferencík M.
      • Krajcovic J.
      Beneficial health effects of milk and fermented dairy products--review.
      [EL4, NE]). Similar to dairy products, food sources of animal proteins are an excellent source of micronutrients.

       Plant Protein Sources: Legumes (Beans and Lentils), Soy Products

      The percentage of protein intake from plants was 34% in the PREMIER trial, primarily from grains (both refined and whole), fruits, vegetables, and nuts and seeds (
      • Lin P.H.
      • Miwa S.
      • Li Y.J.
      • Wang Y.
      • Levy E.
      • Lastor K.
      • Champagne C.
      Factors influencing dietary protein sources in the PREMIER trial population.
      [EL1, RCT]). Nuts, fruits, vegetables, and grains are discussed in either the carbohydrate or fats sections. Although less commonly eaten in the American meal plan, pulses and legumes (which include beans and lentils), are good sources of protein, soluble fiber, and micronutrients. Consumption of legumes more than four times per week as compared to less than once per week is associated with an 11% decrease in CVD risk (
      • Bazzano L.A.
      • He J.
      • Ogden L.G.
      • et al.
      Legume consumption and risk of coronary heart disease in US men and women: NHANES I Epidemiologic Follow-up Study.
      [EL2, PCS]). Bean consumption, analyzed as a separate food from legumes, was associated with lower BMI, waist circumference, SBP, and higher nutrient intake in a cross-section of a nationally representative sample (
      • Papanikolaou Y.
      • Fulgoni III, V.L.
      Bean consumption is associated with greater nutrient intake, reduced systolic blood pressure, lower body weight, and a smaller waist circumference in adults: results from the National Health and Nutrition Examination Survey 1999-2002.
      [EL3, SS]).
      Soybean products, such as tofu and soy milk, have attracted attention due to their effects on LDL-C. Isolated soy protein with isoflavones lowered LDL-C by 3% in RCTs when compared to milk or other proteins (
      • Sacks F.M.
      • Lichtenstein A.
      • Van Horn L.
      • et al.
      Soy protein, isoflavones, and cardiovascular health: an American Heart Association Science Advisory for professionals from the Nutrition Committee.
      [EL4, NE]). The replacement of animal protein sources high in saturated fat with soy products, such as a soy burger in place of a hamburger, may have an additive effect on lowering of LDL-C. The average soy protein consumption in the RCTs was 25 to 50 g/day, which was about half of the total protein intake. Soybeans are high in protein, fiber, PUFAs, vitamins, and minerals. Soy foods can be incorporated into meals in place of animal protein foods; they may also be included as a substitute for carbohydrate and fat calories to increase the total (and plant) protein content of meals.
      Phytoestrogens are present in soybeans and can act as endocrine disruptors. A discussion on this subject is beyond the scope of this guideline, but it is worth noting that the long-term health effects of the phytoestrogens in soybeans are unknown (
      • Patisaul H.B.
      • Jefferson W.
      The pros and cons of phytoestrogens.
      [EL4, NE]). Soy protein in concentrated forms (such as supplements) should be used with caution due to its potential estrogenic effects.

       Fats

      The American Heart Association (AHA) and National Cholesterol Education Program (NCEP)-Adult Treatment Panel (ATP) III guidelines recommend that saturated fat be <7% of total calories for lowering LDL-C. Trans fat should be <1% of total calories, and total cholesterol intake should be <200 to 300 mg/day (NCEP and AHA guidelines, respectively). Unsaturated fats should make up the rest of the recommended 25 to 35% of calories from fat (
      • Otten J.J.
      • Hellwig J.P.
      • Meyers L.D.
      Dietary reference intakes (DRI). The essential guide to nutrient requirements.
      [EL4, NE]). MUFAs can provide up to 20% of total calories, whereas the recommendation for PUFAs is 5 to 10% of calories (
      • National Cholesterol Education Program; National Heart, Lung, and Blood Institue; National Institutes of Health
      Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report.
      [EL4, NE];
      • Abbey M.
      • Noakes M.
      • Belling G.B.
      • Nestel P.J.
      Partial replacement of saturated fatty acids with almonds or walnuts lowers total plasma cholesterol and low-density-lipoprotein cholesterol.
      [EL2, NRCT]). Increased intake of unsaturated fats as compared to saturated fats is associated with better CHD outcomes (
      • Hu F.B.
      • Stampfer M.J.
      • Manson J.E.
      • et al.
      Dietary saturated fats and their food sources in relation to the risk of coronary heart disease in women.
      [EL2, PCS]).
      The focus on markedly decreasing fat ingestion in the 1990s may have contributed to some of the increase in the common chronic diseases such as obesity, DM, and dysmetabolic syndrome. This is because the decrease in fat intake was accompanied by an increase in the ingestion of carbohydrates (principally from refined sources and added sugars) and calories. Clearly, reducing fat intake can be an effective weight-maintenance strategy for some individuals, but fat intake from healthy sources can contribute to CVD risk reduction.

       Omega-3 Fatty Acids: Fish, Flax, Walnuts

      Omega-3 fatty acids are PUFAs that are derived from plant or animal sources. The marine-derived omega-3 fatty acids EPA and DHA have been shown to be cardioprotective (
      • Investigators Gissi-HF
      • Tavazzi L.
      • Maggioni A.P.
      • et al.
      Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial.
      [EL1, RCT]). The evidence for a plant-derived omega-3 fatty acid, alpha-linoleic acid (ALA), is less convincing (
      • Wang C.
      • Harris W.S.
      • Chung M.
      • et al.
      n-3 Fatty acids from fish or fish-oil supplements, but not alpha-linolenic acid, benefit cardiovascular disease outcomes in primary-and secondary-prevention studies: a systematic review.
      [EL4, NE]). Therefore, the source is important when recommending increased intake of omega-3 fatty acids. Increasing intake of omega-3 fatty acids can be achieved via foods or supplements.
      EPA+DHA intake for the prevention of CVD should be at least 500 mg/day, which can be achieved by consuming 2 servings (3.5 ounces) of fatty, cold-water fish (such as salmon or mackerel) per week. Alternatively, this intake may be met with fish oil capsules (
      • Lloyd-Jones D.M.
      • Hong Y.
      • Labarthe D.
      • et al.
      Defining and setting national goals for cardiovascular health promotion and disease reduction: the American Heart Association’s strategic Impact Goal through 2020 and beyond.
      [EL4, NE];
      • Harris W.S.
      • Kris-Etherton P.M.
      • Harris K.A.
      Intakes of long-chain omega-3 fatty acid associated with reduced risk for death from coronary heart disease in healthy adults.
      [EL2, MNRCT]). Patients with CHD should ingest 1 g/day of EPA+DHA, preferably from fatty fish. The intake should be 2 to 4 g/day of EPA+DHA for individuals with elevated TG levels (Table 7) (
      • Kris-Etherton P.M.
      • Harris W.S.
      • Appel L.J.
      • American Heart Association Nutrition Committee
      Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease.
      [EL4, NE]). However, the USDA Dietary Guidelines Advisory Committee has concluded that “moderate evidence shows that consumption of 2 servings (4 oz.) of seafood per week, resulting in an average of 250 mg/d of long-chain omega-3 fatty acids [due to the lack of emphasis on oily fish], is associated with reduced cardiac mortality from CHD or sudden cardiac death in persons with or without CVD” (
      • U.S. Department of Agriculture
      Proceedings of Dietary Guidelines Advisory Committee Meeting, Nov 4-5, 2009.
      [EL4, NE]).
      Table 7Recommended Intakes for Marine-derived Omega-3 Fatty Acids, EPA and DHA for CVD Prevention
      PopulationRecommendation
      Patients without documented CHDEat a variety of (preferably oily) fish at least twice per week, resulting in an average of ~500 mg/d EPA+DHA.

      Include oils and foods rich in α-linoleic acid (flaxseed, canola, and soybean oils; flaxseed and walnuts).
      Patients with documented CHDConsume ~1 g EPA + DHA per day, preferably from oily fish.

      EPA + DHA supplements could be considered in consultation with the physician.
      Patients needing to lower TG (TG>500 mg/dL)2-4 g EPA + DHA per day provided as capsules under a physician’s care.
      Abbreviations: CHD = coronary heart disease; CVD = cardiovascular disease; DHA = docosahexaenoic acid; EPA = eicosapentaenoic acid; TG = triglycerides.
      Adapted from Kris-Etherton et al. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation. 2002;106:2747-2757.
      High-dose EPA+DHA (2 to 4 g/day) is a treatment for TG >500 mg/dL. TG may be lowered through inhibition of TG production in the liver and by affecting genes that control lipolysis and oxidation of fats (
      • Harris W.S.
      • Miller M.
      • Tighe A.P.
      • Davidson M.H.
      • Schaefer E.J.
      Omega-3 fatty acids and coronary heart disease risk: clinical and mechanistic perspectives.
      [EL4, NE]). In addition, there is some evidence, although not conclusive, that EPA+DHA increases HDL-C (
      • Balk E.
      • Chung M.
      • Lichtenstein A.
      • et al.
      Effects of omega-3 fatty acids on cardiovascular risk factors and intermediate markers of cardiovascular disease.
      [EL4, NE]). Some evidence suggests that EPA+DHA increases LDL-C in response to significant TG lowering, which is thought to be due to the increased conversion of very low-density-lipoprotein cholesterol (VLDL-C) to LDL-C (
      • Harris W.S.
      • Miller M.
      • Tighe A.P.
      • Davidson M.H.
      • Schaefer E.J.
      Omega-3 fatty acids and coronary heart disease risk: clinical and mechanistic perspectives.
      [EL4, NE]). Overall, increasing EPA+DHA intake has a favorable effect on the lipid profile.
      Consumption of ~600 mg/day of EPA+DHA decreases SBP and DBP by about 2 mm Hg (
      • Balk E.
      • Chung M.
      • Lichtenstein A.
      • et al.
      Effects of omega-3 fatty acids on cardiovascular risk factors and intermediate markers of cardiovascular disease.
      [EL4, NE]). Omega-3 fatty acids produce eicosanoids that are vasodilatory and improve endothelial function. The slight BP improvements together with other benefits of EPA+DHA reduce CVD risk.
      The plant-derived omega-3 fatty acid ALA may have anti-arrhythmic and anticoagulation properties (
      • Freese R.
      • Mutanen M.
      Alpha-linolenic acid and marine long-chain n-3 fatty acids differ only slightly in their effects on hemostatic factors in healthy subjects.
      [EL2, NRCT];
      • Billman G.E.
      • Kang J.X.
      • Leaf A.
      Prevention of sudden cardiac death by dietary pure omega-3 polyunsaturated fatty acids in dogs.
      [EL2, NRCT]). The Mediterranean meal plan often is higher in ALA due to the emphasis on nuts and seeds as compared to the TLC and DASH meal plans. ALA has been shown to beneficially affect CVD risk factors (see “Nuts” and “Liquid Vegetable Oils” sections below); however, the evidence for EPA+DHA in primary and secondary CVD prevention is stronger (
      • Wang C.
      • Harris W.S.
      • Chung M.
      • et al.
      n-3 Fatty acids from fish or fish-oil supplements, but not alpha-linolenic acid, benefit cardiovascular disease outcomes in primary-and secondary-prevention studies: a systematic review.
      [EL4, NE]).

       Liquid Vegetable Oils

      Liquid vegetable oils are the primary source of PUFAs in the Western meal plan. Corn, safflower, sunflower, and soybean oils (the predominant vegetable oils in the meal plan) are all high in linoleic acid, which is an essential omega-6 fatty acid; flaxseed and canola (rapeseed) oils have appreciable amounts of ALA. Olive oil is high in MUFAs and is encouraged in the Mediterranean dietary pattern.
      Substituting PUFAs, mainly omega-6 fatty acids, for carbohydrates, improved the ratio of TC to HDL-C in a meta-analysis of large epidemiologic studies (
      • Mensink R.P.
      • Zock P.L.
      • Kester A.D.
      • Katan M.B.
      Effects of dietary fatty acids and carbohydrates on the ratio of serum total to HDL cholesterol and on serum lipids and apolipoproteins: a meta-analysis of 60 controlled trials.
      [EL2, MNRCT]). The LDL-lowering effects of omega-6 fatty acids were demonstrated by substituting 10% of calories from saturated fat for omega-6 fatty acids, resulting in a decrease of LDL-C by 18 mg/dL (
      • Mensink R.P.
      • Katan M.B.
      Effect of dietary fatty acids on serum lipids and lipoproteins. A meta-analysis of 27 trials.
      [EL1, MRCT]). Omega-6 PUFA intake should be 5 to 10% of total calories per day for prevention of CVD (
      • Harris W.S.
      • Mozaffarian D.
      • Rimm E.
      • et al.
      Omega-6 fatty acids and risk for cardiovascular disease: a science advisory from the American Heart Association Nutrition Subcommittee of the Council on Nutrition, Physical Activity, and Metabolism; Council on Cardiovascular Nursing; and Council on Epidemiology and Prevention.
      [EL4, NE]).
      Regular ingestion of MUFAs, by replacing 5% of energy from saturated fats, is associated with improved CVD risk (
      • U.S. Department of Agriculture
      Proceedings of Dietary Guidelines Advisory Committee Meeting, Nov 4-5, 2009.
      [EL4, NE]). MUFAs are most often consumed in the form of olive oil and nuts, such as walnuts, macadamia nuts, and almonds (
      • Abbey M.
      • Noakes M.
      • Belling G.B.
      • Nestel P.J.
      Partial replacement of saturated fatty acids with almonds or walnuts lowers total plasma cholesterol and low-density-lipoprotein cholesterol.
      [EL2, NRCT];
      • Garg M.L.
      • Blake R.J.
      • Wills R.B.
      • Clayton E.H.
      Macadamia nut consumption modulates favourably risk factors for coronary artery disease in hypercholesterolemic subjects.
      [EL2, NRCT];
      • Ellsworth J.L.
      • Kushi L.H.
      • Folsom A.R.
      Frequent nut intake and risk of death from coronary heart disease and all causes in postmenopausal women: the Iowa Women’s Health Study.
      [EL2, PCS];
      • Hu F.B.
      • Stampfer M.J.
      Nut consumption and risk of coronary heart disease: a review of epidemiologic evidence.
      [EL4, NE];
      • Fraser G.E.
      Nut consumption, lipids, and risk of a coronary event.
      [EL4, NE];
      • Hu F.B.
      • Stampfer M.J.
      • Manson J.E.
      • et al.
      Frequent nut consumption and risk of coronary heart disease in women: prospective cohort study.
      [EL2, PCS];
      • Fraser G.E.
      • Sabaté J.
      • Beeson W.L.
      • Strahan T.M.
      A possible protective effect of nut consumption on risk of coronary heart disease. The Adventist Health Study.
      [EL2, PCS]). Olive oil and nuts have other beneficial components, such as polyphenols. Many high-MUFA oils are entering the food supply as a substitute for trans fatty acids, including canola, safflower, sunflower, and soybean oils. A study comparing ingestion of virgin olive oil to refined olive oil found decreased LDL-C oxidation in subjects consuming the virgin but not the refined olive oil (
      • de la Torre-Carbot K.
      • Chávez-Servin J.L.
      • Jaúregui O.
      • et al.
      Elevated circulating LDL phenol levels in men who consumed virgin rather than refined olive oil are associated with less oxidation of plasma LDL.
      [EL1, RCT]). The polyphenols present in virgin olive oil but absent in refined olive oil are thought to be responsible for this effect.
      The controversy about the benefits of MUFAs originated from primate studies. A meal plan emphasizing MUFAs resulted in atherosclerotic progression similar to that observed in primates consuming meals high in saturated fat (
      • Rudel L.L.
      • Parks J.S.
      • Sawyer J.K.
      Compared with dietary monounsaturated and saturated fat, polyunsaturated fat protects African green monkeys from coronary artery atherosclerosis.
      [EL1, RCT]). Primates on the high-PUFA meal plan had the least atherosclerotic progression. Assessing atherosclerotic progression in humans is more difficult, and these results have not been replicated in humans.
      In summary, vegetable food sources of MUFAs are cardioprotective.

       Nuts

      Nuts contain unsaturated fats, protein, fiber, and micronutrients but are also high in energy. When tree nuts are incorporated into the meal plan, the LDL-C–lowering effects are 25% greater than would be expected based on blood-cholesterol predictive equations (
      • Griel A.E.
      • Kris-Etherton P.M.
      Tree nuts and the lipid profile: a review of clinical studies.
      [EL4, NE]). A review of large epidemiologic studies showed a 35% decrease in the RR of CHD incidence in individuals who consumed nuts five or more times per week (
      • Kris-Etherton P.M.
      • Hu F.B.
      • Ros E.
      • Sabaté J.
      The role of tree nuts and peanuts in the prevention of coronary heart disease: multiple potential mechanisms.
      [EL4, NE]). A pooled analysis of 25 intervention trials investigating the effects of nut consumption on blood lipid levels found that daily nut consumption of 67 g (2.36 ounces) caused a 5.1% decrease in TC (10.9 mg/dL), 7.4% decrease in LDL-C (10.2 mg/dL), 8.3% decrease in the LDL-C:HDL-C ratio (0.22), and 5.6% decrease in the TC:HDL-C ratio (0.24) (
      • Sabaté J.
      • Oda K.
      • Ros E.
      Nut consumption and blood lipid levels: a pooled analysis of 25 intervention trials.
      [EL2, MNRCT]). The effects were greater in those with higher baseline LDL-C values, lower BMI, and in those eating Western meals. The Portfolio Study emphasized foods or nutrients that decrease TC, including almonds (14 g/1,000 calories), soluble fiber (9.8 g/1,000 calories), soy protein (21.4 g/1,000 calories), and plant sterols (1.0 g/1,000 calories). This meal plan lowered LDL-C by 30%, which is similar to the efficacy of first-generation statins (
      • Jenkins D.J.
      • Kendall C.W.
      • Marchie A.
      • et al.
      Effects of a dietary portfolio of cholesterol-lowering foods vs lov-astatin on serum lipids and C-reactive protein.
      [EL1, RCT]). Endothelial function, related to BP, is improved when the meal plan includes walnuts, which are high in plant-derived omega-3 fatty acids, antioxidants, and L-arginine (
      • Cortés B.
      • Núñez I.
      • Cofán M.
      • et al.
      Acute effects of high-fat meals enriched with walnuts or olive oil on postprandial endothelial function.
      [EL1, RCT]). Types of nuts that decrease CVD risk factors include hazelnuts, peanuts, pecans, some pine nuts, pistachio nuts, macadamia nuts, and walnuts (
      • U.S. Food & Drug Administration
      Qualified Health Claims - Nuts and Heart Disease.
      [EL4, NE]). Almonds, which are seeds, also decrease CVD risk (
      • U.S. Food & Drug Administration
      Qualified Health Claims - Nuts and Heart Disease.
      [EL4, NE]). The current FDA qualified health claim for nuts and CVD states that “scientific evidence suggests but does not prove that eating 1.5 ounces per day of most nuts (such as those specified above) as part of a meal plan low in saturated fat and cholesterol may reduce risk of heart disease” (
      • U.S. Food & Drug Administration
      Qualified Health Claims - Nuts and Heart Disease.
      [EL4, NE]). Nuts, legumes, pulses, and seeds should amount to ≥4 servings per week for CVD prevention (
      • Lloyd-Jones D.M.
      • Hong Y.
      • Labarthe D.
      • et al.
      Defining and setting national goals for cardiovascular health promotion and disease reduction: the American Heart Association’s strategic Impact Goal through 2020 and beyond.
      [EL4, NE]).

      4.Q1.3 Healthy Micronutrient Intake

      Vitamins are organic compounds that are essential in small amounts for normal metabolism. With the exception of vitamin D, vitamins are not synthesized by the body and need to be ingested to prevent certain metabolic disorders. Lack of adequate vitamin intake can lead to obvious clinical vitamin deficiency syndromes but can also lead to subtle effects in otherwise healthy patients or those with chronic disease. Gross vitamin deficiency still occurs in populated areas of the world where meals are poor in nutritional value. Vitamin deficiency is rarely seen in industrialized societies but may occur in the very elderly, vegans, immigrants, the very poor, alcoholism, malabsorption, malabsorptive bariatric surgery, hemodialysis, and inborn errors of metabolism.
      Vitamin B12 deficiency has been reported to be present in 10 to 20% of older adults and is more prevalent in people who follow a vegetarian or vegan meal plan since the major source is meat (
      • Pennypacker L.C.
      • Allen R.H.
      • Kelly J.P.
      • et al.
      High prevalence of cobalamin deficiency in elderly outpatients.
      [EL3, CCS]). Some persons with low-normal serum vitamin B12 levels may in fact be deficient and manifest neurologic, psychologic, or hematologic symptoms or disease (
      • Lindenbaum J.
      • Savage D.G.
      • Stabler S.P.
      • Allen R.H.
      Diagnosis of cobalamin deficiency: II. Relative sensitivities of serum cobalamin, methylmalonic acid, and total homocysteine concentrations.
      [EL3, CCS]). If vitamin B12 deficiency is suspected, even in the presence of low-normal vitamin B12 levels, the diagnosis can be confirmed with measurement of methyl malonic acid. Methyl malonic acid is elevated in the presence of vitamin B12 deficiency. Vitamin B12 deficiency can result from lack of the intrinsic factor needed to bind vitamin B12 for gut absorption. Vitamin B12 deficiency is also found in approximately 15% of adults over 60 years of age due to poorly absorbed protein-bound vitamin B12 (
      • Andrès E.
      • Affenberger S.
      • Vinzio S.
      • et al.
      Food-cobalamin malabsorption in elderly patients: clinical manifestations and treatment.
      [EL3, CCS]). Malabsorption of the food-protein-B12 complex is related to gastric achlorhydria and is often associated with atrophic gastritis. In addition, a RCT involving persons with T2DM treated with metformin or placebo over 4 years revealed an increased risk of vitamin B12 deficiency. In this trial, the absolute risks for vitamin B12 deficiency and low vitamin B12 levels were 7 and 11%, respectively (
      • de Jager J.
      • Kooy A.
      • Lehert P.
      • et al.
      Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: randomised placebo controlled trial.
      [EL1, RCT]). Folate fortification of foods does not seem to mask macrocytic anemia in patients with vitamin B12 deficiency, although this may be possible with high folate supplement use. The National Health and Nutrition Examination Survey (NHANES) data for adults in the post-folate food fortification era found that patients with vitamin B12 deficiency had higher folate levels, were more likely to be anemic, and had more cognitive impairment than those with normal serum folate levels (
      • Morris M.S.
      • Jacques P.F.
      • Rosenberg I.H.
      • Selhub J.
      Folate and vitamin B-12 status in relation to anemia, macrocytosis, and cognitive impairment in older Americans in the age of folic acid fortification.
      [EL2, PCS]). Given the high prevalence of vitamin B12 deficiency and the ease and safety of treatment, some have advocated routinely screening adults over the age of 65 for vitamin B12 deficiency. This policy has not been endorsed in formal guidelines. Whether or not individuals over 50 years of age should take vitamin B12 supplements is unclear. It is prudent to recommend an intake of at least 10 to 15 μg of vitamin B12 daily for older individuals (
      • IOM. Dietary Reference Intakes
      Thiamin, Riboflavin, Niacin, Vitamin B-6, Vitamin B-12, Pantothenic Acid, Biotin, and Choline.
      [EL4, NE]). With the exception of malabsorptive bariatric surgery (Roux-en-Y gastric bypass [RYGB] and biliopancreatic diversion with duodenal switch [BPD-DS]) and pernicious anemia requiring parenteral (IM, SQ, or intranasal) vitamin B12 treatment, patients with vitamin B12 deficiency can generally be treated with oral vitamin B12 (1,000 μg/day of oral crystalline cobalamin). Patients with vitamin B12 deficiency also benefit from increasing the intake of foods rich in vitamin B12, including turkey, pork, eggs, liver, and corned beef (
      • Andrès E.
      • Kaltenbach G.
      • Noblet-Dick M.
      • et al.
      Hematological response to short-term oral cyanocobalamin therapy for the treatment of cobalamin deficiencies in elderly patients.
      [EL2, NRCT];
      • Kuzminski A.M.
      • Del Giacco E.J.
      • Allen R.H.
      • Stabler S.P.
      • Lindenbaum J.
      Effective treatment of cobalamin deficiency with oral cobalamin.
      [EL1, RCT]).
      Vitamin D deficiency is more common than previously believed, especially among adolescents, individuals of increased pigmentation, postmenopausal women, and the elderly. Persons at risk for vitamin D deficiency include those with inadequate sun exposure or oral intake, those who have decreased gut absorption due to malabsorption, and those who have decreased conversion of vitamin D to either 25(OH)D in the liver or subsequent conversion to 1,25-dihydroxyvitamin D (1,25(OH)2D) in the kidney (Table 8; see also discussion on bone health) (
      • Holick M.F.
      • Matsuoka L.Y.
      • Wortsman J.
      Age, vitamin D, and solar ultraviolet.
      [EL4, NE]). Inadequate body stores of vitamin D have been associated with muscle weakness, functional impairment, and increased risk of falls and fractures (
      • Bischoff-Ferrari H.A.
      • Dawson-Hughes B.
      • Willett W.C.
      • et al.
      Effect of Vitamin D on falls: a meta-analysis.
      [EL1, MRCT];
      • Gerdhem P.
      • Ringsberg K.A.
      • Obrant K.J.
      • Akesson K.
      Association between 25-hydroxy vitamin D levels, physical activity, muscle strength and fractures in the prospective population-based OPRA Study of Elderly Women.
      [EL2, PCS]). Lower serum total 25(OH)D concentrations in older persons have also been associated with a greater risk of future nursing home admission (
      • Visser M.
      • Deeg D.J.
      • Puts M.T.
      • Seidell J.C.
      • Lips P.
      Low serum concentrations of 25-hydroxyvitamin D in older persons and the risk of nursing home admission.
      [EL2, PCS]), and up to 50% of the institutionalized elderly have inadequate levels of vitamin D (
      • Holick M.F.
      • Siris E.S.
      • Binkley N.
      • et al.
      Prevalence of Vitamin D inadequacy among postmenopausal North American women receiving osteoporosis therapy.
      [EL3, CSS]). The Control and Prevention has recently reported that the percentage of adults achieving 25(OH)D levels greater than 30 ng/ mL has declined to only 30% in Caucasians and only 5% in African Americans since 1980. During this same time, more individuals have been found to be severely vitamin D deficient (25[OH]D <10 ng/mL) (
      • Ginde A.A.
      • Liu M.C.
      • Camargo Jr., C.A.
      Demographic differences and trends of vitamin D insufficiency in the US population, 1988-2004.
      [EL3, SS]), including children (
      • Kumar J.
      • Muntner P.
      • Kaskel F.J.
      • Hailpern S.M.
      • Melamed M.L.
      Prevalence and associations of 25-hydroxyvitamin D deficiency in US children: NHANES 2001-2004.
      [EL3, SS]).
      Table 8Risk Factors for Vitamin D Deficiency
      • Decreased intake
      • o
        Malnutrition (inadequate oral intake)
      • o
        Decreased sun exposure
      • o
        Increased adiposity
      • o
        Gastrointestinal malabsorption (short bowel syndrome, pancreatitis, inflammatory bowel disease, amyloidosis, celiac sprue, malabsorptive bariatric surgery procedures)
      • Hepatic
      • o
        Some anti-epileptic medications (increased catabolism of 25(OH)D)
      • o
        Severe liver disease or failure (decreased 25-hydroxylase activity)
      • Renal
      • o
        Aging (decreased 1-alpha hydroxylase activity and decreased 7-dehydrocholesterol in skin – precursor to vitamin D)
      • o
        Renal insufficiency, GFR<60% (decreased 1-alpha hydroxylase activity)
      • o
        Nephrotic syndrome (decreased levels of vitamin D-binding hormone)
      At present, there are no guidelines for vitamin D testing, nor are there guidelines for when that testing should occur. However, it should be noted that vitamin D supplementation has been shown to reduce fall frequency by half (
      • Bischoff H.A.
      • Stähelin H.B.
      • Dick W.
      • et al.
      Effects of vitamin D and calcium supplementation on falls: a randomized controlled trial.
      [EL1, RCT]) and to reduce all types of skeletal fracture (
      • Chapuy M.C.
      • Arlot M.E.
      • Duboeuf F.
      • et al.
      Vitamin D3 and calcium to prevent hip fractures in the elderly women.
      [EL1, RCT];
      • Bischoff-Ferrari H.A.
      • Willett W.C.
      • Wong J.B.
      • Giovannucci E.
      • Dietrich T.
      • Dawson-Hughes B.
      Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials.
      [EL1, MRCT]). Higher serum total 25(OH)D concentrations (e.g., 34 ng/mL versus 20 ng/mL) have been associated with greater calcium absorptive efficiency (
      • Heaney R.P.
      • Dowell M.S.
      • Hale C.A.
      • Bendich A.
      Calcium absorption varies within the reference range for serum 25-hydroxyvitamin D.
      [EL1, RCT]), and several studies suggest that a minimum level of 30 ng/mL (i.e., 75 nmol/L; 1 ng/mL = 2.5 nmol/L) is needed to prevent secondary hyperparathyroidism, a known cause of bone loss (
      • Holick M.F.
      • Siris E.S.
      • Binkley N.
      • et al.
      Prevalence of Vitamin D inadequacy among postmenopausal North American women receiving osteoporosis therapy.
      [EL3, CSS];
      • Thomas M.K.
      • Lloyd-Jones D.M.
      • Thadhani R.I.
      • et al.
      Hypovitaminosis D in medical inpatients.
      [EL3, CCS];
      • Chapuy M.C.
      • Preziosi P.
      • Maamer M.
      • et al.
      Prevalence of vitamin D insufficiency in an adult normal population.
      [EL3, CSS]). Based on bone health, where there is strength of data, the Institute of Medicine (IOM) recommendations for vitamin D RDAs are 600 IU/day for ages 1 to 70 years and 800 IU/day for ages 71 years and older (Table 9), corresponding to a serum 25(OH)D level of at least 20 ng/mL (50 nmol/L). RDA recommendations meet the requirements of at least 97.5% of the population (
      Dietary Reference Intakes for Calcium and Vitamin D.
      [EL1, MRCT]). On the other hand, PTH plasma levels begin to rise at a total vitamin D level of 78 nmol/L (31.2 ng/mL) (
      • Chapuy M.C.
      • Preziosi P.
      • Maamer M.
      • et al.
      Prevalence of vitamin D insufficiency in an adult normal population.
      [EL3, CSS]). Thus, endocrinology specialty societies recommend raising total vitamin D levels to over 30 ng/mL, which requires 600 to 2,000 IU/ day of vitamin D (
      • Holick M.F.
      • Binkley N.C.
      • Bischoff-Ferrari H.A.
      • et al.
      Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline.
      [EL4, NE];
      • Watts N.B.
      • Bilezikian J.P.
      • Camacho P.M.
      • et al.
      American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the diagnosis and treatment of postmenopausal osteoporosis: executive summary of recommendations.
      [EL4, NE]).
      Table 9Dietary Reference Intakes for Calcium and Vitamin D
      For infants, Adequate Intake is 200 mg/day for 0-6 months of age and 260 mg/day for 6-12 months of age.
      ,
      For infants, Adequate Intake is 400 IU/day for 0-6 months of age and 400 IU/day for 6-12 months of age.
      Life stage groupCalciumVitamin D
      Estimated average requirement (mg/day)RDA (mg/day)UL Intake (mg/day)Estimated Average Requirement (IU/day)RDA (IU/day)UL Intake (IU/day)
      Infants 0 to 6 monthsaa1,000bb1,000
      Infants 6 to 12 monthsaa1,500bb1,500
      1-3 years old5007002,5004006002,500
      4-8 years old8001,0002,5004006003,000
      9-18 years old1,1001,3003,0004006004,000
      19-50 years old8001,0002,5004006004,000
      51-70 year old males8001,0002,0004006004,000
      51-70 year old females1,0001,2002,0004006004,000
      >70 years old1,0001,2002,0004008004,000
      14-18 years old, pregnant or lactating1,1001,3003,0004006004,000
      19-50 years old, pregnant or lactating8001,0002,5004006004,000
      Abbreviations: RDA = recommended daily allowance; UL = upper limit.
      a For infants, Adequate Intake is 200 mg/day for 0-6 months of age and 260 mg/day for 6-12 months of age.
      b For infants, Adequate Intake is 400 IU/day for 0-6 months of age and 400 IU/day for 6-12 months of age.
      With the exception of fatty fish, the vitamin D content of most foods is low to nonexistent. Foods fortified with vitamin D, including dairy products, represent the major source of vitamin D. Regardless, for individuals to reach a level of 30 ng/mL, vitamin D intake needs to be greater than the current IOM recommendations. This will often require the use of vitamin D supplements.
      The 2005 Dietary Guidelines for Americans recommend that older adults, people with increased skin pigmentation, and those exposed to insufficient sunlight increase vitamin D intake from vitamin D-fortified foods and/or supplements (
      • U.S. Department of Agriculture
      Dietary Guidelines for Americans.
      [EL4, NE]). These recommendations were updated in 2010 (
      • U.S. Department of Agriculture
      Dietary Guidelines for Americans.
      [EL4, NE]). Individuals in these high-risk groups should consume at least 1,000 IU (or 25 μg; 1 μg = 40 IU) of vitamin D daily to maintain adequate blood concentrations of 25(OH)D. 25(OH)D is the best laboratory indicator of vitamin D body stores. Routine monitoring of serum total 25(OH)D levels in high-risk individuals is recommended, with the goal of achieving levels of about 30 ng/mL, depending on the individual patient’s clinical status (
      • Holick M.F.
      • Binkley N.C.
      • Bischoff-Ferrari H.A.
      • et al.
      Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline.
      [EL4, NE];
      • Watts N.B.
      • Bilezikian J.P.
      • Camacho P.M.
      • et al.
      American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the diagnosis and treatment of postmenopausal osteoporosis: executive summary of recommendations.
      [EL4, NE]).
      Adopted from: IOM, Food and Nutrition Board. Dietary Reference Intakes: Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. Washington, DC: National Academy Press, 2011.

       Evidence-Based Recommendations for Daily Allowances

      DRIs represent four concepts (Table 10): the RDA, adequate intake (AI), estimated average requirement, and tolerable upper limit (TUL). DRIs are established in the United States by the National Academy of Sciences, National Research Council, and the IOM (Table 11). For practical clinical purposes, the RDA reflects the average daily intake that is sufficient to meet the dietary requirement of nearly all healthy people. The AI is used when the RDA cannot be determined, as is the case for vitamin D and vitamin K. The Daily Value (DV) is set by the FDA and is used on food and supplement labels. The FDA DVs for food labels are based on a 2,000 calorie per day meal plan. However, an individual’s DRI for any nutrient may be higher or lower depending upon the calorie intake needed above or below a 2,000 calorie per day meal plan. A better estimate for any given individual’s DRI nutrient needs can be assessed with the use of a government web site that takes into consideration a person’s gender, age, height, weight, and activity level to estimate the daily DRI and TUL for vitamins and minerals (

      U.S. Department of Agriculture. Interactive DRI for Healthcare Professionals. Availble at: http://fnic.nal.usda.gov/interactiveDRI/dri_results.php. [EL4, NE]

      [EL4, NE]). This can be a helpful aide for use by the population at large to provide nutrient education and to help insure that otherwise healthy individuals taking supplements are within their estimated bodily need.
      Table 10Terms Used for the Intake of Food and Supplement Vitamins and Minerals
      Recommended Dietary Allowance (RDA): The amount of each vitamin and mineral needed to meet the daily needs of nearly all healthy people as determined by the Food and Nutrition Board of the IOM. RDAs for vitamins and minerals are based on gender, age, and physical condition (e.g., pregnancy, lactation, etc.)
      Adequate Intake (AI): An AI is a recommended intake level of certain nutrients based on estimates of how much healthy people need. It is used when there is not enough data to establish an RDA for a vitamin or mineral (e.g., vitamins D and K).
      Daily Value (DV): The DV is set by the FDA and is used on food and supplement labels. DVs for food labels are based on a 2,000 calorie/day diet. An individual’s DV may be higher or lower depending upon calorie intake need above or below a 2,000 calorie/day diet.
      • USP Verified: The initials USP on a label ensure that the food or supplement meets the standards for strength, quality and purity established by the testing organization U.S. Pharmacopeia or other third party verification services. The FDA Good Manufacturing Practices regulation is intended to ensure the quality and purity of all dietary supplements in the U.S. by 2010.
      • Percent Daily Value: The percent DV is the percentage of the DV that 1 serving of food or supplement provides to meet the RDA/AI for a given calorie/day diet.
      Tolerable Upper Limit (TUL), to caution against excessive intake of nutrients (like vitamin A) that can be harmful in large amounts. This is the highest level of daily consumption that current data have shown to cause no side effects in humans when used indefinitely without medical supervision.
      Table 11Recommended Daily Allowance (RDA), Adequate Intake (AI), and Tolerable Upper Limit (TUL) of Selected Vitamins for Adults >18 Years of Age
      More detailed information can be obtained at The National Academies web site http://www.nap.edu/topics.php?topic=287.
      Vitamin (measured unit)RDA/AI MenRDA/AI WomenTULSelected Food Sources [Examples]Function (F) and Increased Need(N)Adverse Effects (AE), & AE Risk (R)
      Vitamin A (international units)300023309990Liver, egg yolk, yellow-green vegetables [6000 IU in a small 5 inch carrot], milkF: vision, immune function, bone and tissue growth. N: BPD-DS bariatric surgery, malabsorptionAE: Liver toxicity R: alcoholism, tobacco smokers, liver disease
      Vitamin D (international units)400-600400-6002000Fortified dairy-foods [100 IU in 8 oz milk], fish oilsF: bone-muscle health. N: bone loss, pigmentation, CKD, RYGB, malabsorption, aging, steroidsAE: renal stones, hypercalciuria, hypercalcemia (rare)
      Vitamin E (milligrams)15151000Vegetable oils, unprocessed cereals, grains, nuts [7 mg/oz almonds], fruit, meatF: antioxidant., rbc and immune function N: malabsorptionAE: cancer risk, possible bleeding
      Vitamin C (milligrams)90752000Citrus juice, fruits [70 mg in 1 orange], tomatoes, broccoliF: antioxidant, iron absorption, wound healing. N: smokersAE: renal stones, Gl upset
      B1 -thiamine (milligrams)1.21.1(ND)Fortified-enriched-whole grains [breads, cereals], porkF: muscle, heart, nerve function N: RYGB, malabsorption, dialysis, alcohol >1/dayAE: none known
      B2-riboflavin (milligrams)1.31.1(ND)Dairy, eggs, grains, nuts, spinachF: skin, eye, nerve function; coenzyme for redox reactionsAE: none known
      B3-niacin (milligrams)161435Lean & organ meats, poultry, fish [11 mg in in 3 oz tuna], peanuts, brewers yeastF: gut, skin, hair, eye, nerve function; coenzyme for redox energy metabolism. N: dialysisAE: flushing, rash, Gl upset
      B5-pantothenic acid (milligrams)55(ND)Whole grains, oats, cereals, organ meats, egg yolk, yeastF: coenzyme in fatty acid metabolismAE: none known
      B6-pyridoxine (milligrams)1.3-1.71.3-1.5100Fortified-en riched-whole grains, nuts, peas, bananas [0.4 mg in 1 banana], fishF: rbc and brain function, protein metabolism. N: tobacco smokers, alcohol >1/dayAE; sensory neuropaty, skin lesions
      B9-folic acid

      (micrograms)
      4004001000Fortified grains, spinach, legumes, avocados, fruitsF: rbc metabolism, cell growth N: pregnancy, alcohol >1/dayAE: may mask vitamin B12 deficiency
      B12-cobalomine

      (micrograms)
      2.42.4(ND)Meats, fish [5 mcg in 3 oz salmon], poultry, fortified foods (cereals)F: rbc, nerve and brain function. N: achlorhydria, aging, vegans, alcohol >1/day, RYGBAE: none known
      Biotin

      (micrograms)
      3030(ND)Liver; less in other meats and fruitsF: coenzyme for synthesis of glycogen, fat, proteinAE: none known
      The table provides selected food sources for vitamins, vitamin functions, patients who may be in need (N) of more intake than the stated RDA/AI, adverse effects (AE) of excess vitamin supplementation (there are no AE noted from food intake only), and clinical settings of increased risk (R) for vitamin deficiency.
      a More detailed information can be obtained at The National Academies web site http://www.nap.edu/topics.php?topic=287.
      With the exception of vitamin D intake and specific use for vitamin deficient states or disease, there is little evidence that supplemental vitamin intake above the RDA/ AI is beneficial for otherwise healthy adults consuming healthy meals. However, it is important to note that many Americans, at least 20 to 30% in some surveys, take over-the-counter herbal or nutritional supplements (
      • Foster D.F.
      • Phillips R.S.
      • Hamel M.B.
      • Eisenberg D.M.
      Alternative medicine use in older Americans.
      [EL3, SS];
      • Eisenberg D.M.
      • Davis R.B.
      • Ettner S.L.
      • et al.
      Trends in alternative medicine use in the United States, 1990-1997: results of a follow-up national survey.
      [EL3, SS]). A readily accessible web site to help physicians, other health care providers, and patients learn the benefits, risks, and nutrient-drug interactions of dietary supplements is the Natural Medicines Comprehensive Database (

      TherapeuticResearch. Natural Medicines Comprehensive Database. Available at: http://naturaldatabase.therapeuticresearch.com/home.aspx?cs=&s=ND. 2011. [EL4, NE]

      [EL4, NE]). This database is a complete and reliable natural medicine resource to provide available health information on all herbal and nonherbal supplements.

       Evidence-Based Use of Multivitamins

      Natural foods such as whole grains, dairy products, fruits, and vegetables contain a variety of nutrients and compounds that provide benefits not available in supplements and which may act synergistically to support health (Table 5). Of concern is the report from The Dietary Guidelines for Americans that the American populace consumes insufficient amounts of green leafy vegetables, fresh fruits, whole grains, and fiber and eats excessive amounts of refined carbohydrates, saturated fat, and sodium (
      • U.S. Department of Agriculture
      Dietary Guidelines for Americans.
      [EL4, NE]). The intake of unbalanced meals raises concern for inadequate intake of healthy micronutrient vitamins and minerals necessary for bodily health. MVI supplements are widely used in the United States, often in the hope of maintaining health, increasing energy, and reducing the risk of cancer, CVD, and other chronic diseases (Table 12). In fact, MVIs are the most common supplements used in America, with one in three adults taking an MVI regularly. MVI use is responsible for $23 billion in annual sales in the United States (
      • National Institutes of Health State-of-the-Science Panel
      National Institutes of Health State-of-the-Science Conference Statement: multivitamin/mineral supplements and chronic disease prevention.
      [EL4, NE]). Of note however, is that no supplement trial in otherwise healthy adults has ever been able to reproduce the health benefits of eating adequate amounts of fresh fruits and vegetables. In addition, the results of both observational and randomized controlled studies to date are not compelling to support a role for either most individual vitamin supplements studied or for a single MVI in the prevention of CV events or mortality from CVD or cancer.
      Table 12Vitamin Content of Commonly Available Multivitamins
      A unitsD unitsE unitsK unitsC mgB1 mgB2 mgB3 mgB5 mgB6 mgB9 mcgB12 mcgBiotin mcgFe mgZn mgCu mgMisc. Notes
      Centrum®35004003025601.51.72010240063018110.5Ca 200 mg, I 150 mcg, Mg 50 mg, Se 55 mcg, Cr 35 mcg
      Centrum Silver®25005005030601.51.7201034002530--110.5Ca 220 mg, I 150 mcg, Mg 50 mg, Se 55 meg, Cr 45 mcg
      One A Day® Womens25008003025601.51.7105240063018152Ca 450 mg, Mg 50 mg, Se 20 mcg, Cr 120 mcg
      One A Day® Men’s Health35004004520901.21.716534001830--152Ca 210 mg, Mg 120 mg, Se 105 meg, Cr 120 mcg, Lycopene 600 mcg
      Therapeutic-M® Theragran-M®500040060289033.42010640012309152Ca 40-66 mg, I 150 mcg, Cr 50 mcg, Se 70 mcg
      Flintstones Complete®300040030--601.51.71510240064018122Ca 100 mg, I 150 meg, Mg 20 mg
      Prenatal (Natal Care Plus®)400040022--1201.8320--10100012--27252Ca 200 mg
      ADEKs High Potency9000400150150601.21.310101.52001250--7.5--Contents reflect adult dose as 2/day
      Dialyvite®--------1001.51.720101010006300------Ca 100 mg, I 150 mcg, Mg 20 mg
      Key: Ca: calcium, I: iodine, Mg: magnesium, Se: selenium, Cr: chromium, B1: thiamine, B2: riboflavin, B3: niacin, B5: pantothenic acid, B6: pyridoxine, B9: folic acid, B12: cobalamin, Fe: iron, Zn: zinc, Cu: copper
      Note: Flintstones Complete® now has 600 IU vitamin D.
      Four organizations comprise The National Academies: the National Academy of Sciences, the National Academy of Engineering, the IOM, and the National Research Council. The goal of these organizations is to produce reports to help shape sound policies, inform public opinion, and advance the pursuit of science, engineering, and medicine.
      There is substantial observational and RCT data for the benefit of calcium and vitamin D use in reducing fractures (
      • Jackson R.D.
      • LaCroix A.Z.
      • Gass M.
      • et al.
      Calcium plus vitamin D supplementation and the risk of fractures.
      [EL1, RCT]) and colorectal cancer (
      • Wactawski-Wende J.
      • Kotchen J.M.
      • Anderson G.L.
      • et al.
      Calcium plus vitamin D supplementation and the risk of colorectal cancer.
      [EL1, RCT]), selenium supplementation in reducing the risk of skin and other cancers (
      • Clark L.C.
      • Combs Jr., G.F.
      • Turnbull B.W.
      • et al.
      Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial.
      [EL1, RCT];
      • Hurst R.
      • Hooper L.
      • Norat T.
      • et al.
      Selenium and prostate cancer: systematic review and meta-analysis.
      [EL1, MRCT];
      • Lee E.H.
      • Myung S.K.
      • Jeon Y.J.
      • et al.
      Effects of selenium supplements on cancer prevention: meta-analysis of randomized controlled trials.
      [EL1, MRCT]), folate intake in relation to CVD (
      • Davey Smith G.
      • Ebrahim S.
      Folate supplementation and cardiovascular disease.
      [EL4, NE]), and fetal neural tube defects with both food fortification (
      • Ray J.G.
      • Meier C.
      • Vermeulen M.J.
      • Boss S.
      • Wyatt P.R.
      • Cole D.E.
      Association of neural tube defects and folic acid food fortification in Canada.
      [EL3, SS]) and oral folate supplements (
      • Laurence K.M.
      • James N.
      • Miller M.H.
      • Tennant G.B.
      • Campbell H.
      Double-blind randomised controlled trial of folate treatment before conception to prevent recurrence of neural-tube defects.
      [EL1, RCT]). Other vitamin studies report evidence of harm and it seems unwise to extrapolate dietary nutrient associations to possible effects from isolated supplements or MVI use. A recent National Institutes of Health (NIH) state-of-the-science conference on MVIs and mineral supplements concluded that there is no consistent evidence that any single vitamin supplement or MVI helps prevent a wide range of diseases (
      • Huang H.Y.
      • Caballero B.
      • Chang S.
      • et al.
      The efficacy and safety of multivitamin and mineral supplement use to prevent cancer and chronic disease in adults: a systematic review for a National Institutes of Health state-of-the-science conference.
      [EL1, MRCT]). In addition, supplement trials have had to be stopped prematurely due to unexpected adverse events (
      • Prentice R.L.
      Clinical trials and observational studies to assess the chronic disease benefits and risks of multivita-min-multimineral supplements.
      [EL4, NE]).
      Several large early cohort studies have reported decreased CVD rates among individuals who self-selected for higher intakes of vitamin E though meals and/or supplements. In addition, several observational and case-control studies have reported reduced rates of cancer among persons who self-selected for higher antioxidant use. However, in a randomized trial of 39,876 women (≥45 years of age) provided vitamin E (600 IU on alternate days), there was no overall benefit for major CV events (RR, 0.93 for any of nonfatal myocardial infarction, nonfatal stroke, or CV death) or cancer after 10 years of follow-up (
      • Lee I.M.
      • Cook N.R.
      • Gaziano J.M.
      • et al.
      Vitamin E in the primary prevention of cardiovascular disease and cancer: the Women’s Health Study: a randomized controlled trial.
      [EL1, RCT]). A follow-up Selenium and Vitamin E Cancer Prevention Trial (SELECT) to evaluate supplement use for prostate cancer prevention was stopped early because of (nonsignificant) increases in prostate cancer and DM versus control subjects (
      • Lippman S.M.
      • Klein E.A.
      • Goodman P.J.
      • et al.
      Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT).
      [EL1, RCT]). A meta-analysis of vitamin E trials reported a mild increase in all-cause mortality with vitamin E use (
      • Miller III, E.R.
      • Pastor-Barriuso R.
      • Dalal D.
      • Riemersma R.A.
      • Appel L.J.
      • Guallar E.
      Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality.
      [EL1, MRCT]).
      Three intervention trials have studied the use of β-carotene for lung cancer prevention. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study randomly assigned 29,133 Finnish male smokers to supplemental β-carotene (20 mg/day) or α-tocopherol (vitamin E) versus placebo (
      [EL1, RCT]). After 5 to 8 years of follow-up, β-carotene use increased the RR of lung cancer (1.18) and total mortality (RR, 1.08) without any reduction in cancer. A second large study was the Carotene and Retinol Efficacy Trial (CARET), which involved random assignment of 18,314 smokers, former smokers, and asbestos-exposed patients to a combination of β-carotene (30 mg/day) plus retinol (25,000 IU/day) versus placebo. The trial was stopped after 4 years due to a significant increased risk in the β-carotene plus retinol group for lung cancer (RR, 1.28), CVD mortality (RR, 1.26), and total mortality (RR, 1.17), without any significant decline in lung cancer (
      • Omenn G.S.
      • Goodman G.E.
      • Thornquist M.D.
      • et al.
      Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease.
      [EL1, RCT]). In the Physicians’ Health Study, 22,071 American male physicians (age 40 to 84 years, 11% smokers and 39% former smokers) were randomly assigned to receive β-carotene (50 mg) or aspirin compared to placebo. After 12 years, there were no differences between the β-carotene and placebo groups for risk of any cancer, CVD, or total mortality (
      • Hennekens C.H.
      • Buring J.E.
      • Manson J.E.
      • et al.
      Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease.
      [EL1, RCT]).
      Table 11 summarizes the RDA, AI, and upper limit (UL) of vitamins for adults. It is important to note that nutritional deficiencies are very common after malabsorptive bariatric surgery (RYGB less so than very long-limb RYGB and BPD-DS) and often occur despite supplementation with a standard MVI (
      • Allied Health Sciences Section Ad Hoc Nutrition Committee
      • Aills L.
      • Blankenship J.
      • Buffington C.
      • Furtado M.
      • Parrott J.
      ASMBS Allied Health Nutritional Guidelines for the Surgical Weight Loss Patient.
      [EL4, NE]). The reported incidence of specific deficiencies after RYGB varies widely in the literature, between 10 to 50% for vitamin B12 and iron (
      • Alvarez-Leite J.I.
      Nutrient deficiencies secondary to bariatric surgery.
      [EL4, NE];
      • Bloomberg R.D.
      • Fleishman A.
      • Nalle J.E.
      • Herron D.M.
      • Kini S.
      Nutritional deficiencies following bariatric surgery: what have we learned?.
      [EL4, NE];
      • Ledoux S.
      • Msika S.
      • Moussa F.
      • et al.
      Comparison of nutritional consequences of conventional therapy of obesity, adjustable gastric banding, and gastric bypass.
      [EL3, CSS]) and 0 to 40% for folic acid (
      • Xanthakos S.A.
      • Inge T.H.
      Nutritional consequences of bariatric surgery.
      [EL4, NE]). Hypovitaminosis D with secondary hyperparathyroidism has been reported in up to 80% of patients both before and after gastric bypass (
      • Ybarra J.
      • Sánchez-Hernandez J.
      • Gich I.
      • et al.
      Unchanged hypovitaminosis D and secondary hyperparathyroidism in morbid obesity after bariatric surgery.
      [EL3, CSS]). In a 2-year retrospective study after RYGB surgery, 137 patients were given a standardized MVI and followed with laboratory testing at 3, 6, 9, 12, 18, and 24 months for vitamin and mineral deficiencies. Three months after RYGB, 34% of these patients required at least 1 specific supplement in addition to the MVI, and at 6 and 24 months this proportion increased to 59 and 98%, respectively. Two years after RYGB, a mean of 3 specific supplements were required for each patient, to include vitamin B12, iron, calcium, vitamin D, and folic acid (
      • Gasteyger C.
      • Suter M.
      • Gaillard R.C.
      • Giusti V.
      Nutritional deficiencies after Roux-en-Y gastric bypass for morbid obesity often cannot be prevented by standard multivitamin supplementation.
      [EL2, PCS]). Lifelong regular follow-up is needed after malabsorptive bariatric surgery to detect and treat vitamin and mineral deficiencies (
      • Heber D.
      • Greenway F.L.
      • Kaplan L.M.
      • et al.
      Endocrine and nutritional management of the post-bariatric surgery patient: an Endocrine Society Clinical Practice Guideline.
      [EL4, NE]).

      4.Q2 What Nutritional Recommendations are Appropriate for Weight Management?

      Eat little, sleep sound. ~Iranian Proverb
      He that eats till he is sick must fast till he is well. ~
      English Proverb

      4.Q2.1 Approach to Overweight and Obesity

      Fat mass (adiposity), as measured by BMI, is strongly associated with an increased risk of hypertension, dyslipidemia, and hyperglycemia. Primary disturbances in adipose tissue anatomy and function adiposopathy are etiologic in the development of these metabolic derangements (
      • Gonzalez-Campoy J.M.
      • Bays H.
      • Mechanick J.I.
      Obesity and Bariatric Endocrinology.
      [EL4, NE];
      • Bays H.E.
      • González-Campoy J.M.
      • Henry R.R.
      • et al.
      Is adiposopathy (sick fat) an endocrine disease?.
      [EL4, NE];
      • Bays H.E.
      • González-Campoy J.M.
      • Bray G.A.
      • et al.
      Pathogenic potential of adipose tissue and metabolic consequences of adipocyte hypertrophy and increased visceral adiposity.
      [EL4, NE]). The disturbances in adipocyte tissue anatomy and function include adipose tissue hypertrophy and inflammation and altered adipokine activity (
      • Bays H.E.
      • González-Campoy J.M.
      • Bray G.A.
      • et al.
      Pathogenic potential of adipose tissue and metabolic consequences of adipocyte hypertrophy and increased visceral adiposity.
      [EL4, NE]). Thus, obesity is viewed as a primary, chronic disease by the World Health Organization (WHO) (
      • World Health Organization
      The Asia-Pacific Perspective: Redefining Obesity and its Treatment.
      [EL4, NE];
      [EL4, NE]), a position long held by TOS and recently officially taken by AACE (
      • Mechanick J.I.
      • Garber A.J.
      • Handelsman Y.
      • Garvey W.T.
      American Association of Clinical Endocrinologists’ position statement on obesity and obesity medicine.
      [EL4, NE]). People with overweight or obesity who after a thorough history and physical examination, including appropriate laboratory testing, do not have any documentable complications of the disease, are at very high risk for eventually developing them. This tenet is central to a preventive medicine approach to metabolic diseases.
      There is an increased risk of mortality once BMI increases to more than 25 kg/m2 in the United States Caucasian population. Expected life span is reduced by 9 years in a person with a BMI >30 kg/m2 compared to someone with a BMI of 20 to 22 kg/m2 (
      • NAO
      Tackling obesity in England.
      [EL4, NE]). These BMI cutoff points are not generalizable to different racial and ethno-cultural groups. In particular, in Southeast Asian, Chinese, and Asian Indian populations, CV risk increases at a BMI cutoff level of 23 to 24 kg/m2 (
      • World Health Organization
      The Asia-Pacific Perspective: Redefining Obesity and its Treatment.
      [EL4, NE]).
      Healthy eating plays a major role in helping individuals lose excess fat mass, and traditionally this has been the goal of treatment. The concept that adipose tissue dysfunction plays a major role in the genesis of metabolic disorders is now well established in the literature (
      • Gonzalez-Campoy J.M.
      • Bays H.
      • Mechanick J.I.
      Obesity and Bariatric Endocrinology.
      [EL4, NE];
      • Bays H.E.
      • González-Campoy J.M.
      • Henry R.R.
      • et al.
      Is adiposopathy (sick fat) an endocrine disease?.
      [EL4, NE];
      • Bays H.E.
      • González-Campoy J.M.
      • Bray G.A.
      • et al.
      Pathogenic potential of adipose tissue and metabolic consequences of adipocyte hypertrophy and increased visceral adiposity.
      [EL4, NE];
      • van de Woestijne A.P.
      • Monajemi H.
      • Kalkhoven E.
      • Visseren F.L.
      Adipose tissue dysfunction and hypertriglyceridemia: mechanisms and management.
      [EL4, NE];
      • Villa J.
      • Pratley R.E.
      Adipose tissue dysfunction in polycystic ovary syndrome.
      [EL4, NE];
      • Xu X.
      • Ying Z.
      • Cai M.
      • et al.
      Exercise ameliorates high-fat diet-induced metabolic and vascular dysfunction, and increases adipocyte progenitor cell population in brown adipose tissue.
      [EL2, NRCT];
      • Rizza S.
      • Cardellini M.
      • Porzio O.
      • et al.
      Pioglitazone improves endothelial and adipose tissue dysfunction in pre-diabetic CAD subjects.
      [EL1, RCT];
      • Giorgino F.
      Adipose tissue function and dysfunction: organ cross-talk and metabolic risk.
      [EL4, NE];
      • Wood I.S.
      • de Heredia F.P.
      • Wang B.
      • Trayhurn P.
      Cellular hypoxia and adipose tissue dysfunction in obesity.
      [EL4, NE];
      • Iwai M.
      • Horiuchi M.
      Role of renin-angiotensin system in adipose tissue dysfunction.
      [EL4, NE];
      • Yildiz B.O.
      • Azziz R.
      • Androgen Excess and PCOS Society
      Ovarian and adipose tissue dysfunction in polycystic ovary syndrome: report of the 4th special scientific meeting of the Androgen Excess and PCOS Society.
      [EL4, NE];
      • Blüher M.
      Adipose tissue dysfunction in obesity.
      [EL4, NE];
      • Hajer G.R.
      • van Haeften T.W.
      • Visseren F.L.
      Adipose tissue dysfunction in obesity, diabetes, and vascular diseases.
      [EL4, NE];
      • Rebolledo O.R.
      • Marra C.A.
      • Raschia A.
      • Rodriguez S.
      • Gagliardino J.J.
      Abdominal adipose tissue: early metabolic dysfunction associated to insulin resistance and oxidative stress induced by an unbalanced diet.
      [EL2, NRCT];
      • Goossens G.H.
      The role of adipose tissue dysfunction in the pathogenesis of obesity-related insulin resistance.
      [EL4, NE];
      • Chudek J.
      • Wiecek A.
      Adipose tissue, inflammation and endothelial dysfunction.
      [EL4, NE];
      • Garg A.
      Adipose tissue dysfunction in obesity and lipodystrophy.
      [EL4, NE];
      • Bays H.E.
      Adiposopathy is “sick fat” a cardiovascular disease?.
      [EL4, NE];
      • Appachi S.
      • Kelly K.R.
      • Schauer P.R.
      • et al.
      Reduced cardiovascular risk following bariatric surgeries is related to a partial recovery from “adiposopathy”.
      [EL2, PCS];
      • Bays H.E.
      • Laferrère B.
      • Dixon J.
      • et al.
      Adiposopathy and bariatric surgery: is ‘sick fat’ a surgical disease?.
      [EL4, NE]). Thus, moving forward, a major focus of nutrition counseling for overweight or obesity is to correct adiposopathy. This evidence base supports the critical role of healthy eating in risk reduction for various disease states. Table 13 outlines weight-loss therapies appropriate for use at different BMI levels, with different comorbidities, for the largely Caucasian American population (
      • National Institutes of Health
      Clinical Guidelines on the identification, evaluation, and treatment of overweight and obesity in adults. The evidence report.
      [EL4, NE];

      National Institutes of Health-North American Association for the Study of Obesity. The practical guide. Identification, evaluation and treatment of overweight and obesity in adults. Available at: http://www.nhlbi.nih.gov/guidelines/obesity/prctgd_c.pdf. 2000. NIH Publication Number 00-4084. [EL4, NE]

      [EL4, NE]).
      Table 13Therapies Appropriate for Use at Different BMI Levels with Different Comorbidities
      BMI → Classification →18.5-24.9 Normal25-29.9 Overweight30-34.9 Obesity class I35-39.9 Obesity class II40 Obesity class III
      Risk of complicationsVery lowMildModerateHighExtreme
      Medical nutrition therapyXXXXX
      Physical activityXXXXX
      Behavior modificationXXXXX
      PharmacotherapyXXXX
      SurgeryX (gastric banding only)XX
      Abbreviation: BMI = body mass index.
      Adult feeding behavior is rooted from childhood experiences. Therefore, it is important to consider the role that adults play in rearing children, since a number of factors within the home environment have been associated with healthy eating. Both household food availability (foods present in the house) and accessibility (whether available food is in a form or location that facilitates their consumption, such as fruit on the counter) have been positively associated with healthful meal intake in youth (
      • Cullen K.W.
      • Baranowski T.
      • Owens E.
      • Marsh T.
      • Rittenberry L.
      • de Moor C.
      Availability, accessibility, and preferences for fruit, 100% fruit juice, and vegetables influence children’s dietary behavior.
      [EL3, SS]). Home availability and taste preferences are the strongest correlates of fruit and vegetable intake among adolescents (
      • Neumark-Sztainer D.
      • Wall M.
      • Perry C.
      • Story M.
      Correlates of fruit and vegetable intake among adolescents. Findings from Project EAT.
      [EL3, SS]). On the other hand, availability of less healthy options, such as soft drinks in the home, is associated with increased soft drink consumption among children (
      • Grimm G.C.
      • Harnack L.
      • Story M.
      Factors associated with soft drink consumption in school-aged children.
      [EL3, SS]).
      Social environmental influences within the home, such as modeling of healthful dietary intake by parents and more frequent family meals, may promote healthy eating among children and adolescents. Parental food and vegetable intake has been associated with fruit and vegetable intake among youth (
      • Cooke L.J.
      • Wardle J.
      • Gibson E.L.
      • Sapochnik M.
      • Sheiham A.
      • Lawson M.
      Demographic, familial and trait predictors of fruit and vegetable consumption by pre-school children.
      [EL3, CSS];
      • Fisher J.O.
      • Mitchell D.C.
      • Smiciklas-Wright H.
      • Birch L.L.
      Parental influences on young girls’ fruit and vegetable, micronutrient, and fat intakes.
      [EL3, SS];
      • Hanson N.I.
      • Neumark-Sztainer D.
      • Eisenberg M.E.
      • Story M.
      • Wall M.
      Associations between parental report of the home food environment and adolescent intakes of fruits, vegetables and dairy foods.
      [EL3, CSS]). Parental feeding style may also have a bearing on children’s food intake. Parental practices, such as restricting foods, pressuring children to eat, or using foods as rewards, may inadvertently promote behaviors contrary to their intentions (