NIH Presentation Nutritional Counseling and Dietetics Practice in Sickle Cell Disease

Nutritional Counseling and Dietetics Practice in Sickle Cell

DiseaseNutrition and Hemoglobinopathies Working Group

August 24, 2010

Jean Ann Olds MS RDDirector, TCH Clinical Nutrition

Current State of Dietetics Practice in Hemoglobinopathies

• Nutrition issues in hemoglobinopathy patients are usually referred to Oncology/BMT Dietitian

• Nutrition assessment occurs when issues are present, anticipatory guidance does not occur.

• Standards of practice for hemoglobinopathies within our Professional Association (ADA) are limited

• More data is needed to establish guidelines and competencies for hemoglobinopathies

Nutritional Characteristics of SCD: Overview

For SS and SB0 Thal: • Increased Resting Energy

Expenditure• Increased protein turnover• Increased bone turnover• Deficiencies of vitamins, minerals,

trace elements• Decreased bone mineral density• Amino acid deficiencies

Growth in Sickle Cell Anemia

• Show a reduction in height and weight by 2 years of age

• Delayed pre-pubertal growth spurt• Trends toward increasing deficits

with increasing age

Causes of Poor Growth: Increases in REE

• REE is 6-22 % higher in SCD • Protein turnover is 44-100%

higher in SCD than in controls• Increased protein turnover and

caloric expenditure is thought due to the hyperactive bone marrow in chronic hemolysis

Low Z Scores for Growth:

• Weight• Height• Arm circumference• Upper arm fat and muscle area

Growth Differences con’t…• In normal populations, growth studies

comparing caucasians to Africans/Caribbeans show Africans have greater height, weight, and BMI than Caucasians

• SCD patients compared to Africans have significantly lower BMI although similar BMI to Caucasians

• This indicates that when compared to ethnically matched controls, SCD patients have more growth deficits than when compared to Caucasians—we may be underestimating the growth deficit in SCD

Patey RA, Sylvester KP, Rafferty GF, Dick M, Greenough A. The importance of using ethnically appropriate reference ranges for growth

assessment in sickle cell disease. Arch Dis Child. 2002;87:352-353.

Growth Differences con’t…• In comparison to CDC norms,

male SCD patients are three times more likely to be underweight in adolescence

• Females with SCD were three times more likely to be obese in adolescence in comparison to CDC norms

• BMI attained in adolescence can be predicted by gender, average weight in childhood, and the number of emergency department visits.

Mitchell MJ, Carpenter GJO, Crosby LE, Bishob CT, Hines JH, Noll J. Growth status in children and adolescents with sickle cell disease. Pediatr Hematol Oncol. 2009;26:237-250.

Bone Health in SCD• Significant increases in bone

turnover have been documented in adolescents with SCD

• One researcher feels that “osteoporosis may be one of the major public health problems in SCD patients “

• One study observed a prevalence of 79.6 % low Bone Mineral Density in a group of 103 SCD patients. Sarrai M, Duroseau H, D'Augustine J, Moktan S, Bellevue R. Bone mass density in adults with sickle cell disease. Br J

Haematol. 2007;136:666-672.

Bone Health con’t…• The likelihood of developing low

BMD decreased with increasing BMI.

• low hemoglobin levels were the strongest predictor of low BMD in SCD.

• The patients with low bone density

had low Vitamin D levels and low serum zinc levels

Calorie Intake• 2000 Study of calorie intake show

SCD patients consume 39% of normal kcals for age during admission for pain crises

• 2-6 weeks after the pain crises, intake improves to only 80% of normal for age.

• Studies suggest repeated bouts of acute illness cause an overall energy deficit in this population

• Intake of all nutrients declines further with age

Malinauskas BM, Gropper SS, Kawchak DA, Zemel BS, Ohene-Frempong K, Stallings VA. Impact of acute illness on nutritional status of infants and young children with sickle cell disease. J Am Diet Assoc. 2000;100:330-334

Williams R, Olivi S, Mackert P, Fletcher L, Tian GL, Wang W. Comparison of energy prediction equations with measured resting energy expenditure in children with sickle cell anemia. J Am Diet Assoc. 2002;102:956-961

Boys

Modified World Health Organization Equation (kcal/day)

Age 3-10 years:Modified REE = (22.7 × weight in kg+ 495) × (1.3074 – 0.0309 × Hgb)

Girls Modified REE = (22.5 × weight in kg + 499) × (1.4775 – 0.0309 × Hgb)

Dietary Intake in SCD

• A 3 year study reported in 2007 found normal energy intake, high protein intake and low %DRI intake for E, D, calcium, and folate at baseline

• Subsequently, intake for all major nutrients, protein, and energy declined with age

Kawchak DA, Schall JI, Zemel BS, Ohene-Frempong K, Stallings VA. Adequacy of dietary intake declines with age in children with sickle cell disease. J Am Diet Assoc. 2007;107(5):843-848.

Amino Acids in SCD

• Of the 13 amino acid deficiencies known in SCD three have had supplementation trials

• Arginine• Glutamine• Citrulline

Glutamine Supplementation in SCD

• Supplementation with glutamine results in decreased REE, improved %IBW, triceps skinfold and muscle strength

• Another study shows improved minute ventilation and exercise endurance

• Supplementation also decreased oxidative susceptibility of sickle RBC

Arginine Supplementation

• Supplementation of 0.1 – 0.5 gm/kg resulted in increased nitric oxide production during VOC (2000)

• 0.05 to 0.1 gm/kg/d supplements did not show a change in arginine levels or a clinical benefit for pediatric SCD patients (2007)

• In 2007 study: if arginine levels were not increased, was this enough arginine to show a clinical benefit?

Vitamin/Mineral Status in SCD

• Studies in SCD point to deficiencies in Vitamins D, E, A, C, B6, B12

• Multi Vitamin preparations containing adequate amounts of vitamins and minerals low in SCD do not exist

• Supplementation amounts needed are not known for all nutrients

Vitamin A Status• Vitamin A status in SCD known to

be suboptimal, one study documented < 30 ug/dL in 66% of SC patients

• One study supplemented Vitamin A at RDA level which did not impact serum levels, suggesting therapeutic dose is needed

• Poor vitamin A status was associated with poor growth, worse hematologic status, and increased risk of hospitalizations for SCD-related events

Vitamin C Status

• Numerous studies document poor Vitamin C status in SCD

• Dietary intake of Vitamin C appeared to be normal, pointing to increased utilization

Chiu, D, Vichinsky E, Ho SL, Liu T, Lubin BH. Vitamin C deficiency in patients with sickle cell anemia. Am J Pediatr Hematol Oncol. 1990;12(3):262-267.

Vitamin C in SCD …Supplementation of Vitamin C:• reduced blood pressure, • increased packed cell volume,• Increased hemoglobin

concentration, • Increased % fetal hemoglobin, • reduced irreversibly sickled cells, • Increased resistance of the cells to

lysis

Vitamin D Status in SCD• Low Vitamin D status was found in

65 % of HbSS subjects during one sampling, and in 100% of subjects during a sampling of the same population in the spring

• Children with low Vitamin D status consumed significantly less Vitamin D and calcium

• Deficiency was felt to be combination of poor intake, dark skin pigmentation, and additional unknown factors related to SCD

Magnesium Status in SCD• 1997 Italian study showed erythrocyte

Mg content in SS and SC erythrocytes is reduced compared with normal controls

• This thought to be due to increased activity of Na/Mg exchanger and increased free Mg, causing Mg gradient to be outwardly directed

• Mg content of erythrocytes was increased by use of 500 mg Mg supplementation for 4 weeks

• Increased Mg content blocked the K-Cl cotransport pathway, which normally dehydrates the cell

Use of Ionized Magnesium• Differences in magnesium levels

were only found by measuring serum ionized magnesium, not total serum magnesium levels

• Studies have found a significant low correlation between total and ionized magnesium (r2 = 0.38)

• Significant differences in SCD and control magnesium levels would have been missed by only measuring total serum magnesium levels

Use of Calcium/Magnesium Ratios• Measurement of ionized Calcium to

ionized Magnesium ratios in SCD frequently results in significantly high levels which are abnormal

• High Ca2+/Mg2+ ratios are linked to vascular diseases such as atherosclerosis, migraines, strokes, and hypertension in non-SCD patients.

• Increased Ca2+/Mg2+ ratio is known to enhance vascular tone and result in increased arteriolar resistance at the intravascular level.

• This potential for magnesium related vasculopathy may be greater for SCD patients because low serum ionized magnesium levels have been documented in SCD patients

Zehtabchi S, Sinert R, Rinnert S, Chang B, Heinis C, Altura RA, Altura BT, Altura BM. Serum ionized magnesium levels and ionized calcium-to-magnesium ratios in adult patients with sickle cell anemia. Am J Hematol.

2004;77:215-222

Results of Improved Magnesium Status

• Erythrocyte K-Cl cotransport significantly reduced

• Reduction in absolute reticulocyte count

• Improved hydration of the erythrocytes

• Supplementation of Magnesium for 6 months resulted in a significant reduction in the number of painful episodes as well as reduction of the number of dense sickle cell erythrocytes

Zinc in SCD• Zinc status is now known to be

deficient in SCD• Poor zinc status may not correlate

to low serum zinc measurement in the blood

• Patients given 10 mg daily of Zinc showed increased linear growth and muscle mass even when their serum zinc was normal

Zinc…

• The growth hormone IGF-1 requires zinc to function1

• Zinc status needs to be optimized before growth hormone treatment

• Otherwise, growth hormone treatment may not yield optimal results

Omega 3 Fatty Acids in SCD• Supplementing SCD patients with

3 grams menhaden fish oil daily decreased frequency of pain episodes by approximately half

• There was no associated increase in prothrombin time

Omega-3 fatty acid deficiency in sickle cell disease correlates with clinical severity and has therapeutic implications. Blood. 2007;110(11):12B.

More Nutrition Research Needed

• Guidelines for routinely determining the need for and providing nutrients known to be deficient in SCD need to be developed

• Supplementation with glutamine has shown the possibility that supplying deficient micronutrients has the potential for decreasing energy expenditure

• More research is needed to determine the potential for improved nitrogen balance, decreased protein turnover, and decreased energy expenditure when all micronutrients are being adequately provided, as well as the impact this could have on disease severity, complications, and quality of life in SCD

Assessment: Fluid• Fluid is the most important basic

element of diet assessment• Fluid hand-outs have been

developed specific to sickle cell disease

• Fluid is recommended at 1 -1.5 X normal maintenance fluid for weight

• Fluid hydrates the red cell, decreases potential for sickling, and decreases constipation

 Body Weight (pounds) Daily Recommendations (Number of 8-oz Servings/Day)

 10-24  2-3

 25-29  4-6

 30-44  5-8

 45-54  6-9

 55-75  7-10

 75-99  8-11

 100-129  9-13

 130-149  10-15

 150-174  11-17

 >175  12-18

FLUID GUIDE

Energy and Protein Assessment• Equations developed at St Jude

are utilized for calculation of REE including factor for patient’s usual Hemoglobin

• Energy then recommended at 1.5 to 1.75 X the Sickle Cell REE calculation

• Protein assessed at 1.5 X RDA, due to increased protein turnover—most SCD patients already have protein intake over 2 X RDA

Sample High Calorie Diet Breakfast

2.5 meat exchanges4 fat exchanges1.5 milk exchanges2 fruit exchanges

Sample High Calorie Diet

Breakfast

2 scrambled eggs with ½ ounce cheese 2 sausage links 1 medium blueberry muffin with 1

teaspoon butter and 2 teaspoons jam 6 ounces custard yogurt 8 ounces orange juice

Sample High Calorie Diet Snack

2 fruit exchanges2 milk exchanges2 fat exchanges

Sample High Calorie Diet

Snack Fruit smoothie: ½ cup fruit (mango,

strawberry, banana, etc), 6 ounces yogurt or ice cream blended with 2 ice cubes, 2 tablespoons peanut butter, 4 ounces whole milk

Sample High Calorie Diet Lunch 2 high fat meat exchanges3 bread exchanges2 fruit exchanges1 milk exchange2 fat exchanges

Sample High Calorie Diet Lunch

Grilled cheese with 2 slices of cheese and thin slices

½ cup fruit canned in heavy syrup ½ cup sweet potato french fries 8 ounces whole milk

Sample High Calorie DietSnack:1 milk exchange2 fruit exchanges1 fat exchange

Evening Meal 3 meat exchanges2.5 starch exchange4 fat exchanges2 fruit exchanges1 milk exchange1 vegetable exchange

Sample High Calorie Diet Snack:6 ounces pudding with 2 tablespoons

whipped cream ½ cup sliced strawberries Evening Meal Fried chicken drumstick and thigh ¾ cup mashed potatoes with 2

tablespoons sour cream ½ cup broccoli with ¼ cup cheese sauce 3-inch square piece of cornbread with 1

tablespoon butter and 1 tablespoon honey

8 ounces whole chocolate milk

Sample High Calorie Diet

3,655 kcal 126 g protein

392 g carbohydrate 176 g fat

Diet HistoryDiet History must carefully assess:

• Protein intake/zinc intake• Dairy or substitute intake• Fiber/Whole Grains• Presence of constipating foods• High antioxidant fruits and vegetables• Supplementation history

Nutrition Support in SCD• One study examined nasogastric tube feedings

in 5 male patients with sickle cell disease • Of the 5 patients in the study, only 2 received

tube feedings.• These 2 patients experienced accelerated

growth and a reduction in the incidence and severity of complications.

• A third patient received nightly oral supplements.

• Two patients received dietary counseling plus supplemental iron, zinc, folate, and vitamin E with no benefit.

• Why are tube feedings so rarely used in this population?

Heyman MB, Katz R, Hurst D, Chiu D, Ammann AJ, Vichinsky E, Gaffield B, Castillo R, Kleman K, Thaler MM, Lubin B.  Growth retardation in sickle cell disease treated by nutritional support.  Lancet. 1985;20:903-906.

Heyman MB, Katz R, Hurst D, Chiu D, Ammann AJ, Vichinsky E, Gaffield B, Castillo R, Kleman K, Thaler MM, Lubin B.  Growth retardation in sickle cell disease treated by nutritional support.  Lancet. 1985;20:903-906.

Constipation• SCD patients have low fiber

intakes• African patients in particular have

high intake of white flour, meat, and rice

• Frequent use of narcotic pain medications increases tendency for constipation, especially during admissions for pain

• Is not uncommon for SCD patients to be admitted for abdominal pain which originates from constipation

Diet Counseling• Intake of high antioxidant fruits and

vegetables is encouraged• African American children frequently favor

dark green and yellow vegetables although families may not be serving them often enough

• African families tend to consume dark green and yellow vegetables daily

• Both African and African American families under utilize dairy products and fruit as snacks

• Successful snack strategies similar to other disease states-- well balanced snacks are added after school and at bedtime

• Calorie supplements are usually needed• Multi-vitamin without iron is always

recommended

Factors to Consider For Better Nutritional Strategies in SCD

• Should ADEKS be considered? 1) Vitamin A may be too high 2) Is Vitamin K dose appropriate? • Dairy Intake: Lactose intolerance may

be less of an issue than lack of desire for milk products. Yogurt, cheese, flavored milk should be encouraged

• Fiber and whole grain intake--especially brown rice in African families-- problematic in this population

• Diet tends to be low in magnesium

•Supplements to consider: Magnesium (adult studies use 540 mg daily or approximately 5-7 mg/kg daily)

•Vitamin D: therapeutic if indicated, or 2000 IU daily •Calcium if indicated by diet history, or to accompany therapeutic Vitamin D dose•Bone Density normals for SCD need to be developed, since marrow may be enlarged. • Measurement protocol should be developed in childhood and measured with regularity over lifespan

Strategies to Consider for Better Nutritional Status in

SCD, con’t

Strategies for Better Nutritional Status in SCD,

con’t

•Take supplemental calories following each pain crisis or hospitalization• Vitamin A supplement: how much?? •Fish Oil: DHA/EPA Supplements: 3000 mg for over age 14, 1500 mg under age 14•Arginine: how much?

0.2 to 0.3 gm/kg daily of Arginine•Stress that all supplements to be

coordinated with physician

How to Meet Nutritional Needs?

• Diet alone is not likely to meet needs of SCD patients

• Optimization of diet and diet counseling remains ESSENTIAL given the amount of nutrients that are likely required

• It is not optimal to supplement a poor diet

How to Meet Nutritional Needs?

• How will it be possible to give this population the number of supplements in a form that they are likely to take?

• The answer is likely to be in the form of a daily regimen of several vitamin capsules plus a drink containing needed amino acids

Nutrition Assessment Needed!

The need for regular assessments and counseling by registered

dietitians will need to be established by clinical data

supporting improved outcomes in SCD with good nutritional status, similar to the role of nutrition in diseases such as Cystic Fibrosis. The need for tube feedings

needs to be as strongly considered as in other disease

states.