1. Nutrition Implications of Starvation and Refeeding Syndrome
Hannah Tower
Concordia college
Moorhead, MN

2. Objectives
Describe the pathophysiology of starvation and refeeding syndrome (RFS)
Explain and identify signs and symptoms along with risk factors of starvation and RFS
Be able to recognize a patient at risk of starvation and RFS
Describe the medical nutrition therapy (MNT) for starvation and RFS
Describe ways to prevent starvation and RFS

3. What is RFS?
Term used to describe several metabolic alterations that occur during nutritional repletion of starved patients
Electrolyte depletion
Fluid shifts
Glucose derangements
Can occur when reinstating nutrition orally, enterally, or parenterally
It was first reported among those released from concentration camps after WWII
Talk about Keys study
Long, S., Nelms, M., & Suchner, K. (2007).
Marinella, M. A. (2003).

4. Pathophysiology: Early Fasting State
Tissues cannot get their energy from ingested glucose and other macromolecules
Glycogenolysis
Gluconeogenesis assists in maintaining blood glucose levels
Glucose from the liver to the muscles comes from the recycling of lactate and glycogenolysis
Rate of glucose use is greater than production by gluconeogenesis and the stores diminish rapidly
Few hours after eating
Hepatic glycogenolysis is the major provider of glucose to the blood
Gropper, S. S., Smith, J. L., & Groff, J. L. (2009).

5. Pathophysiology: Fasting State
18-48 hours of no food intake
Amino acids from muscle protein breakdown provide the main substrate for gluconeogenesis
The shift to gluconeogenesis is signaled by the secretion of glucagon
Ketogenic amino acids released by muscle protein hydrolysis are converted into ketones
Large daily loses of nitrogen in the urine
Gropper, S. S., Smith, J. L., & Groff, J. L. (2009).
Tresley, J., Sheean, P. M. (2008).

6. Pathophysiology: Starvation State
Goal: spare body protein
Fat stores  main energy source
The shift to fat breakdown releases large amounts of glycerol
Assure a continued supply of glucose as fuel for the brain
Eventually ketosis occurs
Ketone bodies are delivered to skeletal muscle, heart, and brain
Survival time
3 months
When the fat reserves are depleted the body uses essential protein
Loss of liver and muscle function and eventually death
- Antibodies: fight infections, enzymes: catalyze life-sustaining reactions, hemoglobin: transport oxygen to tissues
- FA fuel the heart, liver, and skeletal muscle tissues. Brain cant use fatty acids for energy b/c they cannot cross the blood-brain barrier, shift to fat breakdown releases large amounts of glycerol which replace AA as the major gluconeogenic precursor, assuring a continued supply of glucose as fuel for the brain, brain and skeletal muscle also adapt to use ketone bodies for energy
Ketosis: ketone body concentraiton in the blood rises and they are delivered through the bloodstream to skeletal muscle, heart, and brain which oxidize them instead of glucose. As long as ketone bodies are maintained at a high concentration the need for glucose and gluconeogenesis is reduced, which spares valuable protein
Survival time depends on the amount of fat stores, normal person about 3 months
Gropper, S. S., Smith, J. L., & Groff, J. L. (2009).

7. Pathophysiology of RFS
Reintroduction of carbohydrates (CHO) causes increase in insulin production
Body fluid disturbances
Fluid overload  pulmonary edema
Hyperglycemia
Thiamin deficiency
Electrolyte depletion
Phosphate
Potassium
Magnesium
The sudden swing from fat and protein catabolism to CHO metabolism stimulates a great increase in insulin production which results in intracellular shift of glucose with cellular uptakes of phosphate, magnesium, and potassium
- Fluid overload occurs from the sodium retention effects of hyperglycemia and hyperinsulinemia. The introduction of CHO reduces sodium and water excretion, resulting in the expansion of the extracellular fluid compartment and pulmonary edema
Boateng, A. A., Sriram, F., Meguid, M. M., & Crook, M. (2010)

8. Boateng, A. A., Sriram, F., Meguid, M. M., & Crook, M. (2010)

9. Hyperglycemia Blood glucose level above normal
Results from glucose introduction into a starved system adopted for fat metabolism
Infections are more common
Thiamin deficiency
Wernicke’s encephalopathy
Infections are more common because hyperglycemia disrupts neutrophilic function
The sudden introduction of glucose drives already depleted stores of thiamin even lower
Boateng, A. A., Sriram, F., Meguid, M. M., & Crook, M. (2010).

10. Thiamin Deficiency
Thiamin is required as a cofactor in the oxidation of CHO
Wernicke’s encephalopathy
Symptoms generally do not appear until refeeding of CHO
Confusion
Ocular disturbances
Ataxia
Coma
Common in alcoholics
- Thiamin requirements are related to CHO intake
Wernicke’s encephalopathy is a neurological disorder resulting from thiamin deficiency which can result in long term neurological damage or death
Ataxia: loss of ability to coordinate muscle movement
Tresley, J., Sheean, P. M. (2008).

11. Hypophosphatemia Low serum phosphate
Moderate: <2.5 mg/dL
Severe: <1.0 mg/dL
Caused by starvation-induced loss of lean tissue mass, minerals, and water
Transcellular shift of phosphorus and a decline in the serum phosphorus
Can lead to:
Irregular heartbeat
Respiratory failure
Confusion
- PREDOMINANT FEATURE OF RFS
- Reintroduction of CHO causes increase in insulin release which induces a transcellular shift of phosphorus and a decline in the serum phosphorus
Marinella, M. A. (2003).
- Tresley, J., Sheean, P. M. (2008).

12. Hypokalemia Low serum potassium
<2.5 mEq/L
Results from the cellular uptake of potassium
Can result in:
Paralysis
Compromised respiratory system
Muscle necrosis
Irregular heartbeat
Cellular uptake of potassium is enduced by insulin produced in response to the nutritional load
Boateng, A. A., Sriram, F., Meguid, M. M., & Crook, M. (2010)
Tresley, J., Sheean, P. M. (2008)

13. Hypomagnesemia Low serum magnesium
<1.0 mg/dL
Results from cellular uptake of magnesium after feeding
Can result in:
Convulsions
Seizures
Boateng, A. A., Sriram, F., Meguid, M. M., & Crook, M. (2010).
Tresley, J., Sheean, P. M. (2008).

14. Risk Factors Anorexia nervosa Prolonged starvation
Prolonged starvation
Marinella, M. A. (2003).
Tresley, J., Sheean, P. M. (2008).

15. Risk Factors cont. Alcoholism Homelessness
Homelessness
Marinella, M. A. (2003).

16. Risk Factors cont. Obesity with significant weight loss
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History of cancer
Marinella, M. A. (2003). The refeeding syndrome and hypophosphatemia. Nutrition Reviews, 61 (9),

17. Risk Factors cont. Prolonged vomiting and diarrhea
Recent major surgery
Depression in the elderly
Poorly controlled diabetes
Prolonged NPO status
Bariatric surgery
Boateng, A. A., Sriram, F., Meguid, M. M., & Crook, M. (2010)

18. Signs and Symptoms CVS GI Neurologic Metabolic Respiratory
Sudden death
Heart failure GI
Anorexia
Abdominal pain
Constipation or diarrhea
Vomiting
Neurologic
Tremors
Coma
Ataxia
Metabolic
Metabolic alkalosis
Metabolic acidosis
Respiratory alkalosis
Respiratory
Respiratory failure
Ventilator dependency
Musculoskeletal
Weakness
Osteomalacia
Ataxia: lack of muscle coordination
Metabolic alkalosis: pH of tissue is elevated beyond the normal range ( )
Metabolic acidosis: When the body produces too much acid, blood pH is less than 7.35
Respiratory alkalosis: low levels of carbon dioxide in the blood due to excessive breathing
Osteomalacia: softening of bones due to lack of vitamin D
Boateng, A. A., Sriram, F., Meguid, M. M., & Crook, M. (2010)
Stanga, Z., Brunner, A., Leuenberger, M., Grimble, R.F., Shenkin, A., Allison, S.P., & Lobo, D.N. (2008).

19. Identifying Patients at a High Risk of RFS
National Institute for Health and Clinical Excellence (NICE) Guidelines
Patient has one or more of the following
BMI < 16 kg/m2
Unintentional weight loss > than 15% (3-6 months)
Little or no nutritional intake >10 days
Low levels of potassium, phosphate or magnesium prior to feeding
OR …
- National Institute for Health and Clinical Excellence (NICE) (2006).

20. Identifying Patients at a High Risk of RFS cont.
Patient has two or more of the following
BMI < 18.5 mg/m2
Unintentional weight loss > than 10% (3-6 months)
Little or no nutritional intake > 5 days
History of:
Alcohol abuse
Insulin
Chemotherapy
Antacids
Diuretics
- National Institute for Health and Clinical Excellence (NICE) (2006).

21. Clinical Indicators Clinical/ History Lab values Height Weight
Blood pressure
BMI
Desirable BMI
% UBW
History of weight changes
Tricep skin fold
Diet history
I & O
Temperature
Edema
Bone pain
Dizziness
Diarrhea/vomiting
Lab values
Serum phosphate
Magnesium
Potassium
Glucose
Sodium
Cholesterol/TG
Serum iron
BUN
Escott-Stump, S. (2012).

22. MNT for RFS
Energy intake should be instituted carefully, and gradually increased over 4-10 days
Supplementation of electrolytes and vitamins can be started before feeding
Monitor fluid administration carefully
General recomendations
Stanga, Z., Brunner, A., Leuenberger, M., Grimble, R.F., Shenkin, A., Allison, S.P., & Lobo, D.N. (2008)

23. MNT for RFS
Days 1-3
Energy: 10 kcal/kg/day (5 kcal/kg/day if BMI <14)
CHO: 50-60%
Protein: 15-20%
Fat: 30-40%
Electrolytes: measure daily during feeding and increase if necessary
Phosphate: mmol/kg/day
Potassium: 1-3 mmol/kg/day
Magnesium: mmol/kg/day
Fluid: restrict to maintain renal function
About mL/kg/day
Sodium
Minerals: 100% DRI
Vitamins: 200% DRI
Thiamine: mg i.v. 30 minutes prior to feeding
Stanga, Z., Brunner, A., Leuenberger, M., Grimble, R.F., Shenkin, A., Allison, S.P., & Lobo, D.N. (2008).

24. MNT for RFS Days 4-6 Days 7-10 Energy: 15-20 kcal/kg/ day
Iron: supplement after day 7
Stanga, Z., Brunner, A., Leuenberger, M., Grimble, R.F., Shenkin, A., Allison, S.P., & Lobo, D.N. (2008).

25. Medications
Replacement of phosphorus, potassium, and magnesium if depleted
Insulin to correct hyperglycemia
100 mg thiamin bolus daily for three days
Other B-complex and vitamins if needed
- Make sure to monitor blood glocose levels during refeeding
Escott-Stump, S. (2012).

26. Current Research No recent randomized, controlled trials exist
Ethical issues
EAL: Does serum prealbumin correlate with weight loss in starvation?
One non-randomized trial found that serum prealbumin does not correlate with weight loss in starvation
Evidence comes from case studies, case series, and cohort studies
- Wagstaff, G. (2011).
- American Dietetic Association (2009).

27. Current Research cont.
Electronic, anonymous, internet survey sent out covering current practice, perceived prevalence of refeeding risk, and opinions on the NICE guidelines.
Target population: RD’s in London working with adults
Response rate: 168 RD’s, 30.8%
Wagstaff, G. (2011).

28. Current Research cont. Results Conclusions
89.8% have read the NICE guidelines
History of nutritional intake and biochemistry are the most important factors when treating RFS
89.5% do not wait for biochemistry to normalize before commencing feeding
31.2% classified and fed pt. 1 according to NICE recommendations
22.7% for pt. 2
19.5% for pt. 3
Conclusions
Limited by small sample size
Inconsistent dietary practices regarding refeeding syndrome
Wagstaff, G. (2011).

29. Keys’ Study
36 young men between the ages of served as volunteer subjects
Study began in 1944 and lasted a year
Control data was obtained for three months
3,492 calories/day
Semistarvation period for six months
Stimulate the quantity and quality of the food available in western and central Europe
1,570 calories/day
Controlled rehabilitation for three months
Franklin, J. C., Schiele, B. C. Brozek, J., Keys, A. (1945).

30. Keys’ Study: Physical Changes
24% body weight loss
Face and body showed great emaciation
Clothes and shoes too large
Muscle wasting
Edema in knees, ankles, and faces
Nails grew slower
Hair loss
Slower wound healing
Muscle cramps and soreness
Tolerance to heat was increased
Cold body temperature
Blackouts and fainting
Inability to focus
Nausea
Decrease in pulse rate
Fatigue and weakness
Loss of ambition
Depression
Polyuria and nocturia
- Franklin, J. C., Schiele, B. C. Brozek, J., Keys, A. (1945).

31. Keys’ Study: Physical Changes cont.-

32. Keys’ Study: Hunger and Appetite
In total starvation the sensation of hunger rapidly disappears, not true in semistarvation
Subjects referred to sensations located in the abdomen
Mild to intense pain
Varied for each subject
- Franklin, J. C., Schiele, B. C. Brozek, J., Keys, A. (1945).

33. Keys’ Study: Eating Habits
Anticipation of eating heightened the craving for food
Each subject defensively guarded his plate
Food had to be very hot in order to be satisfying
During meals they were silent, deliberate, and gave total attention to their food
Played with their food
Spend hours eating their meal
Saved parts of their meal for later
Taste appeal of the meals increased
Food substitution
Gum chewing
Limited to two packs a day
Large amounts of water
Smoking
Coffee and tea
Limited to nine cups per day
It was as though they borrowed heat from their food as a means of conserving energy
As starvation progressed the number of men who toyed and played with their food increased
Toward the end of the starvation some of the men would dawdle and spend almost two hours over a meal that would have previoulsy taken them minutes
Even though they were only fed three different meals over the course of the study the taste appeal of the diet increased rather than decreased
Franklin, J. C., Schiele, B. C. Brozek, J., Keys, A. (1945).

34. Keys’ Study: Rehabilitation Phase
Purpose: measure the relative efficiency of several levels of refeeding in order to secure the most efficient, practical, and economic regimen for dietary rehabilitation
First six weeks: 2,448 calories
Seventh to tenth weeks: 3,257 calories
Eleventh and twelfth weeks: 3,518 calories
Franklin, J. C., Schiele, B. C. Brozek, J., Keys, A. (1945).

35. Keys’ Study: Rehabilitation Stage cont.
At the end of the 12 weeks the subjects
in the highest caloric group regained
<60% of the weight lost
120 calories more
Lowest group
Gained no weight during the first six weeks
Regained 20% of weight lost after the 12 weeks
Recovery from dizziness, apathy, and
lethargy was the most rapid
Little change and some increase in edema
Appetites were insatiable
Frustration with lack of strength and endurance
Follow-up studies made at 33 and 55 weeks after the end of semistarvation showed that the men had returned to their previous weight and that a number of men exceeded their pre-starvation weight.
- Franklin, J. C., Schiele, B. C. Brozek, J., Keys, A. (1945). -

36. Prevention Improve awareness Recognition of patients at risk
General physicians, surgeons, RD’s, nurses
Recognition of patients at risk
Knowing the warning signs and risk factors
Prevent the development of severe symptoms
Lessen the symptoms is RFS has already developed
Hearing, S. D. (2004).
Marinella, M. A. (2003).
Boateng, A. A., Sriram, F., Meguid, M. M., & Crook, M. (2010).

37. Role of the RD
Make recommendations for providing, withholding, or withdrawing nutrition in individual cases
Promote the right of the individual patient
Assist the healthcare team in recognizing RFS
Signs and symptoms
Risk factors

38. Case Study: Hunger Striker
27 y.o. male went on hunger strike for 4 months
Refused any nourishment
Except tea and coffee with sugar
Lost further 2 kg in hospital and became weaker, more inactive, and apathetic
Treated with enteral and parenteral nutrition
1600 kcal/day
Gained 5 kg due to salt and water retention
Hypokalemia, hypomagnesaemia, and hypophosphatemia
200 mg thiamine was administered as well as potassium phosphate for three days (40 mmol) and magnesium sulphate (20mmol)
After three days electrolyte/ mineral concentrations were in the normal range, and three days later oral nutrition was started
Discharged after 57 days
Stanga, Z., Brunner, A., Leuenberger, M., Grimble, R.F., Shenkin, A., Allison, S.P., & Lobo, D.N. (2008).

39. Case Study: Anorexia Nervosa
40 y.o. woman with long standing anorexia
Upon admission
Ankle edema
Hypotension
Phosphate, magnesium, and potassium were low
Oral supplementation of vitamins and electrolytes
Regardless she developed muscle weakness, drowsiness, and rapid heartbeat
I.V. supplements of electrolytes and minerals
Within 2 days muscle weakness and heart rate were resolved and serum electrolyte concentrations were normal -
- Stanga, Z., Brunner, A., Leuenberger, M., Grimble, R.F., Shenkin, A., Allison, S.P., & Lobo, D.N. (2008).

40. Ethical Issues
ADA position: individuals have the right to accept or refuse nutrition and hydration as MNT
Experiments
Can’t ethically subject people to starvation like in Key’s Study
- American Dietetic Association (2008).

41. Summary
Starvation is severe reduction in energy, vitamin, and mineral intake
RFS is a term used to describe several metabolic alterations that occur during nutritional repletion of starved patients
RFS is caused by rapid refeeding after a period of undernutrition
Characterized by hypophosphatemia
Gradually introduce feeding