Medical

Nutrition
Therapy for Anemia
 Introduction
Hemoglobin is a conjugated protein containing
four heme groups and globin; it is the oxygen-
carrying pigment of the erythrocytes(RBC).
The hematocrit is the volume percentage of
erythrocytes in the blood.
Plasma is the liquid portion of whole blood
containing coagulation factors
serum is the liquid portion of whole blood
without coagulation factors.
 Anemia
Definition: deficiency in size or number of red blood cells or amount of
hemoglobin they contain
limits the exchange of oxygen and carbon dioxide between the blood and
the tissue cells.
Not a disease but a symptom of conditions including:
1. extensive blood loss
2. excessive blood cell destruction
3. decreased blood cell formation
4. nutritional
Classification of Anemia
Based on cell size (MCV)
Macrocytic (large) (MCV>94 MCHC> 31)
Normocytic (normal) (MCV82-92 MCH<31)
Microcytic (MCV<80 MCH< 31)
◦ (small/less circulating hemoglobin) e.g iron def anemia & thalassemia

Based on hemoglobin content (MCH)

Hypochromic (pale color)
Normochromic (normal color)
Iron Deficiency Anemia

Characterized by the production of small (microcytic) erythrocytes

and a diminished level of circulating hemoglobin
Last stage of iron deficiency
Represents the end point of a long period of iron deprivation
Causes of
Iron Deficiency Anemia
Nutritional anemia
Inadequate ingestion
Inadequate absorption
Defects in release from stores
Inadequate utilization
Increased blood loss or excretion
Increased requirement
Stages of Iron Deficiency
Stage 1: moderate depletion of iron stores; no dysfunction
Stage 2: Severe depletion of iron stores; no dysfunction
Stage 3: Iron deficiency
Stage 4: Iron deficiency (dysfunction and anemia) - CLINICAL
 Tests for Iron Deficiency
Serum iron: poor indicator, highly variable day to day and during the day
Ferritin - most sensitive—chief storage form of iron; directly proportional to
iron stored in cells
.
Tests for Iron Deficiency
Zinc protoporphyrin/heme ratio (ZPPH) protoporphyrin binds iron to
form heme or zinc to form zinc protoporphyrin
In the presence of iron deficiency, ratio will rise (iron deficiency
defined as ratio>1:12,000)
Not affected by hematocrit or other causes of anemia; specific to iron
deficiency
Tests for Iron Deficiency
Total iron binding capacity (TIBC)—capacity of
transferrin to bind iron
Transferrin—globulin that binds/transports Fe from
gut wall to tissues
Percent saturation of transferrin (calculate by
dividing serum iron by the TIBC)
◦ TIBC increases in iron deficiency
◦ As stored iron falls, saturation of transferrin
decreases
Iron Deficiency:
Clinical Findings
Early Late
Inadequate muscle Defects in epithelial
function tissues
Growth abnormalities Gastritis
Epithelial disorders Cardiac failure
Reduced
immunocompetence
Restless Leg Syndrome
Koilonchia—A Sign of Iron
Deficiency

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Medical Management
Assess for and treat underlying disease
• Oral iron salts
• Oral iron, chelated with amino acids
• Oral sustained-release iron
• Iron-dextran by parenteral administration
Nutritional Management of Iron-
Deficiency Anemia
Increase absorbable iron in the diet
Include vitamin C at every meal
Include meat, fish or poultry at every meal
Decrease tea and coffee consumption
Supplementation for
Iron Deficiency Anemia
Oral iron salts
◦ Ferrous forms better absorbed than ferric (ferrous
sulfate, ferrous lactate, ferrous fumarate)
Best absorbed on an empty stomach but if irritation
occurs, give with meals
Dosage 50-100 mg / 3 times daily of elemental iron for
adults; 4-6 mg/kg body weight for children divided into
3 doses
Generally supplement for 3 months (4-5 months if
taken with meals)
Supplementation for
Iron Deficiency Anemia
If patient fails to respond
May not be taking supplements
May not be absorbing iron (celiac disease, steatorrhea, hemodialysis)
May be bleeding
May need IV iron dextran (can cause allergic reactions)
 Restoring Iron Levels
Factors to consider:
Bioavailability of iron—the lower the Fe stores, the greater the rate of
absorption
Heme sources (meat, poultry, fish (MFP) )— about 15% absorbable
Non-heme iron (grains, vegetables, eggs)—about 3% to 8% absorbable
Enhancers: Vitamin C—binds iron to form a readily absorbed
complex
Inhibitors:
◦ Non-heme iron Inhibitors (phytate in plant-based diets, polyphenols in
black & herbal tea, coffee, wine, legumes, cereals, fruits & veg).
◦ Calcium binds heme & non-heme iron
Iron overload
Excess iron is stored as ferritin and hemosiderin in the macrophages of the liver, spleen,
and bone marrow. The body has a limited capacity to excrete iron. Approximately 1 mg of
iron is excreted daily through the gastrointestinal tract, urinary tract, and skin.
To maintain a normal iron balance, the daily obligatory loss must be replaced by the
absorption of heme and nonheme food iron. Persons with iron overload excrete increased
amounts of iron, especially in the feces, to compensate partially for the increased
absorption and higher stores.
Excessive iron intake usually stems from accidental incorporation of iron into the diet from
environmental sources. In developing countries the iron overload can result from eating
foods cooked in cast iron cooking vessels or contaminated by
iron-containing soils. In developed countries it likely results from excessive intake of iron-
supplemented foods or multivitamin and mineral supplementation containing iron.
Brain iron increases with age, is higher in men, and is abnormally elevated in
neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease
(Bartzokis et al, 2010).
Several gene variants affect iron metabolism and may contribute to early onset of these
conditions.
Disorders Associated with
Iron Toxicity
Thalassemias
Sideroblastic anemias (lack of blood cells)
Chronic hemolytic anemia
Aplastic anemia (body stops producing new blood cells): normochromic-
normocytic anemia accompanied by a deficiency of all the formed
elements in the blood; it can be caused by exposure to toxic chemicals,
ionizing radiation, and medications, although the cause is often
unknown.
Ineffective erythropoiesis (process of producing rbc)
Transfusional iron overload (secondary to multiple blood transfusions),
Alcoholic cirrhosis
 Hemochromatosis
A genetically determined form of iron overload that results in
progressive hepatic, pancreatic, cardiac, and other organ
damage
Absorb 3 times more iron
Hemochromatosis
It is one of the most common genetic disorders in
the U.S.
Will die of iron overload unless they give blood
frequently
Patients absorb three times more iron from food
than other people
Even heterozygotes (have 1 gene) may be at risk
for iron overload, increasing risk of heart disease.
Hemochromatosis: Risk Factors
Higher risk in people of northern European
descent
Men tend to manifest symptoms earlier because
they have no way to dispose of excess iron
(menstruation, pregnancy, lactation)
Men may develop symptoms in their 30s but may
not be diagnosed until their 50s
Women often develop symptoms after menopause
Hepcidin
Peptide synthesized in the liver, principal regulator of systemic iron
homeostasis.
“iron transport from iron-exporting tissues to plasma”
Deficiency underlies most known forms of hemochromatosis.
Hemochromatosis: Symptoms
Joint pain
Fatigue
Lack of energy
Abdominal pain
Loss of sex drive
Heart problems
Abnormal pigmentation of the skin, making it look gray or bronze
Hemochromatosis:
if untreated, may result in
Arthritis
Liver disease: cirrhosis, cancer, liver
failure
Damage to the pancreas, leading to
diabetes
Heart abnormalities, including
arrhythmias and heart failure
Impotence or early menopause
Tumor cell growth and proliferation
Hemochromatosis:
Diagnosis
Testing: serum ferritin and serum iron
concentrations TIBC, and transferrin saturation can
reveal excess stores of iron; followed by HFE
(genetic) test and possible liver biopsy “gold
standard”
Transferrin saturation >50 women/60 men and
serum iron level> 180 mg/dl
Hemochromatosis:
Treatment
iron overload may simultaneously be anemic as a result of damage to
the bone marrow, an inflammatory disorder, cancer, internal bleeding,
or chronic infection.
Iron supplements should not be taken until the cause is known.
 Hemochromatosis:
Treatment
Regular phlebotomy to remove excess iron
Iron depletion with intravenous desferrioxamine-B ,chelating agent, or
EDTA
Avoidance of iron supplements and sources of iron in the diet, especially
heme iron
Avoid alcohol and vitamin C supplements as they enhance absorption.
Vitamin C may release harmful free radicals generating excess iron from
body stores
Avoid iron fortified foods
Awareness of iron cooking vessels
Do not exceed RDA (women 18 mg, pregnancy 27, adult men and women
over 51 is 8 mg
Megaloblastic Anemias
A form of anemia characterized by the presence of
large, immature, abnormal red blood cell
progenitors in the bone marrow
95% of cases are attributable to folic acid or
vitamin B12 deficiency
Both vitamins are essential to the synthesis of nucleoproteins.
Hematologic changes are the same for both; however, the folic acid
deficiency is the first to appear. Normal body folate stores are depleted
within 2 to 4 months in individuals consuming folate-deficient diets. By
contrast, vitamin B12 stores are
depleted only after several years of a vitamin B12–deficient diet.
In persons with vitamin B12 deficiency, folic acid supplementation can
mask B12 deficiency (see Figure 32-3).
In correcting the anemia, the vitamin B12 deficiency may remain
undetected, leading to the irreversible neuropsychiatric damage that is
corrected only with B12 supplementation
 Static Test for Folate/B12 Status
Folate
Measured in whole blood (plasma and cells) and then in the serum
alone
Difference is used to calculate the red blood cell folate concentration
(may better reflect the whole folate pool)
Can also test serum in fasting patient
B12
Measured in serum
Functional Tests for
Macrocytic Anemias
Homocysteine: Folate and B12 are needed to convert homocysteine to
methionine; high homocysteine may mean deficiencies of folate, B12
or B6
Methylmalonic acid measurements can be used along with
homocysteine to distinguish between B12 and folate deficiencies (↑ in
B12 deficiency)
Schilling test: radiolabeled cobalamin is used to test for B12
malabsorption
Folic Acid Deficiency
Tropical sprue; pregnancy; infants born to deficient
mothers
People taking medications chronically that affect
folic acid absorption
Malabsorption syndromes
Increased requirements
Prolonged inadequate diets
Alcoholics
Causes of Folate Deficiency
Inadequate ingestion
Inadequate absorption
Inadequate utilization
Increased requirement
Increased excretion
Increased destruction
Vitamin B12 deficiency can cause folate deficiency due to the
methylfolate trap
 Methylfolate Trap
In the absence of B12,
folate in the body exists
as 5-methyltetrahydro-
folate (an inactive form)
B12 allows the removal
of the 5-methyl group to
form THFA
Stages of Folate Depletion and
Deficiency
Stage I—early negative folate balance (serum
depletion >3 ng/ml)
Stage II—negative folate balance (cell
depletion)
Stage III—damaged folate metabolism with
folate-deficient erythropoiesis … slowed DNA
synthesis
Stage IV—clinical folate deficiency anemia,
elevated MCV and anemia
The common clinical signs of folic acid deficiency include fatigue,
dyspnea, sore tongue, diarrhea, irritability, forgetfulness,
anorexia, glossitis, and weight loss.
Diagnosis of Folate Deficiency
Folate stores are depleted after 2-4 months on deficient diet
Megaloblastic anemia, low leukocytes and platelets
To differentiate from B12, measure serum folate, RBC folate (more
reflective of body stores) serum B12
High formiminoglutamic acid (FIGLU) in the urine also diagnostic
 Managemenet
Before treatment is initiated, it is important to diagnose the cause of the
megaloblastosis correctly. Administration of folate corrects megaloblastosis
from either folate or vitamin B12 deficiency, but it can mask the neurologic
damage of vitamin B12 deficiency, allowing the nerve damage to progress to the
point of irreversibility.
A dosage of 1 mg of folate taken orally every day for 2 to 3 weeks replenishes
folate stores. Maintaining repleted stores requires an absolute minimum oral
intake of 50 to 100 mcg of folic acid daily. When folate deficiency is complicated
by alcoholism, genetic aberrations, or other conditions that suppress
hematopoiesis, increase folate requirements, or reduce folate absorption,
therapy should remain at 500 to 1000 mcg daily.
Symptomatic improvement, as evidenced by increased alertness, cooperation,
and appetite, may be apparent within 24 to 48 hours, long before hematologic
values revert to normal, a gradual process that takes approximately a month.
Medical Nutrition Therapy

After the anemia is corrected, the patient should be instructed to eat at

least one fresh, uncooked fruit, or dark green vegetable or to drink a
glass of vegetable or fruit and vegetable juice daily .
Destroyed by heat
RDA for adults is 400 mcg
Childbearing age and first trimester 600 mcg/day
 Pernicious Anemia

A macrocytic, megaloblastic anemia caused by a deficiency

of vitamin B12.
Usually secondary to lack of intrinsic factor (IF)
May be caused by strict vegan diet
Also can be caused by ↓gastric acid secretion, gastric
atrophy, H-pylori, gastrectomy, disorders of the small
intestine (celiac disease, regional enteritis, resections),
drugs that inhibit B12 absorption including neomycin,
alcohol, colchicine, metformin, pancreatic disease
Causes of Vitamin B12 Deficiency

Inadequate ingestion
Inadequate absorption
Inadequate utilization
Increased requirement
Increased excretion
Increased destruction by antioxidants
Symptoms of
Pernicious Anemia
Paresthesia (especially numbness and tingling in hands and feet)
Poor muscular coordination
Impaired memory and hallucinations
Damage can be permanent
 Vitamin B12 Depletion
Stage I—early negative vitamin B12 balance
Stage II—vitamin B12 depletion
Stage III—damaged metabolism: vitamin B12 deficient
erythropoiesis
Stage IV—clinical damage including vitamin B12 anemia
includes all preceding parameters, including
macroovalocytic erythrocytes, elevated MCV, elevated TCII level
increased homocysteine, methylmalonic acid levels, and myelin
damage. Leukoencephalopathy and autonomic dysfunction occu
with very low serum B12 levels (,200 pg/ ml); psychiatric
changes, neuropathy, and dementia also may occur
Vitamin B12 stores are depleted after several years without vitamin B12 intake.
As a result of normal enterohepatic circulation (i.e., excretion of vitamin B12 and
analogs in bile and resorption of vitamin B12 in the ileum), it generally takes
decades for strict vegetarians who are not receiving vitamin B12
supplementation to develop a vitamin B12 deficiency.
Treatment of B12 Deficiency
Before 1926 was incurable; until 1948 was treated
with liver extract
Now treatment consists of IM/ SC injection of 100
mcg of vitamin B12 once per week until resolved,
then as often as necessary
Also can use very large oral doses (1000) or nasal
gel
MNT: high protein diet (1.5 g/kg) with meat, liver,
eggs, milk, milk products, green leafy vegetables
Medical Nutrition Therapy
MNT: high protein diet (1.5 g/kg) for liver function
and blood regeneration
meat, liver, eggs, milk, milk products are rich
sources
Increased amounts of green leafy vegetables
…contain iron and folic acid
Diabetics on metformin / above age 51 – atrophic
gastritis
Other Nutritional Anemias
Copper deficiency anemia
Anemia of protein-energy malnutrition
Sideroblastic (pyridoxine-responsive) anemia
Vitamin E–responsive (hemolytic) anemia
 Anemia of Protein-Energy
Malnutrition
Protein is essential for the proper production of hemoglobin and RBCs. Because of the
reduction in cell mass and thus oxygen requirements in protein-energy malnutrition
(PEM), fewer RBCs are required to oxygenate the tissue. Because blood volume remain
the same, this reduced number of RBCs with a low hemoglobin level hypochromic,
normocytic anemia), which can mimic an iron deficiency anemia, is actually a physiolog
(nonharmful) rather than harmful anemia. In acute PEM, the loss of active tissue mass
may be greater than the reduction in the number of RBCs, leading to polycythemia (an
increase in RBCs where they make up a larger proportion of the blood volume). The bo
responds to this RBC production, which is not a reflection of protein and amino acid
deficiency but of an oversupply of RBCs. Iron released from normal RBC destruction is n
reused in RBC production, but is stored so that iron stores are often adequate. Iron
deficiency anemia can reappear with rehabilitation when RBC mass expands rapidly.
The anemia of PEM may be complicated by deficiencies of iron and other nutrients and
associated infections, parasitic infestation, and malabsorption. A diet lacking in protein
usually deficient in iron, folic acid, and, less frequently, vitamin B12.
The nutrition counselor plays an important role in assessing recent and typical dietary
intake of these nutrients.
 Copper Deficiency
“cerulpolasmin” is Copper containing protein
responsible for mobilization of iron from storage sites
to plasma
In copper deficient state, result is low serum iron and
hemoglobin, even when iron stores are normal
Copper is widespread in foods and needed in tiny
amounts
Sometimes occurs in infants fed deficient formula or
cow’s milk, adults and children with malabsorption or
on TPN without copper
Diagnosis is important, since more iron won’t help and
may interfere with copper absorption
Sideroblastic Anemia (Pyrodixine
responsive)
Derangement in the final pathway of heme
synthesis... Immature RBC
Microcytic, hypochromic form
High serum and tissue iron levels
Buildup of immature sideroblasts—hence the name
B6 is essential 50-200 mg —must replace 25 to 100
times the RDA; may need lifelong replacement
Pyridoxine-responsive anemia, distinguished from
anemia caused by pyridoxine deficiency “no
neurologic and cutaneous manifestations”
Hemolytic Anemia
Defects in RBC membranes … Oxidative damage to
cells—lysis occurs
Caused by shortened survival of mature RBC.
Vitamin E is an antioxidant that seems to be
protective.
This anemia can occur in newborns, especially
preemies.
Nonnutritional Anemias
Sports anemia (hypochromic microcytic transient anemia)
Anemia of pregnancy
Anemia of inflammation, infection, or malignancy (anemia of chronic
disease)
Sickle cell anemia
Thalassemias
Anemia of pregnancy
A physiologic anemia is the anemia of pregnancy
Related to increased blood volume and usually resolves with the end of
the pregnancy.
However, demands for iron during pregnancy also are increased so that
inadequate iron intake may also play a role in whether it develops.
 Anemia of Chronic Disease
Occurs from inflammation, infection or malignancy because decreased RBC
production as a result of disordered iron metabolism,
Ferritin levels are normal/increased
Serum iron levels and TIBC are low.
Mild and normocytic. Should not be mistaken for iron deficiency anemia “iron
supplements are not recommended”
Recombinant erythropoietin therapy – drugs to stimulate red blood cells
production.
 Sickle Cell Anemia
Chronic hemolytic anemia , called “Hemoglobin S disease” as a
result of homozygous inheritance of hemoglobin S results in
defective hemoglobin synthesis producing sickle-shaped RBCs
“can not carry oxygen well”
die in 10-20 days “faster than normal RBCs”
Symptoms also include episodes of pain results from the
occlusion of small blood vessels by the abnormally shaped RBC
especially in the abdomen.
 Sickle Cell Anemia

Hemolytic anemia+ vasoocclusive … impaired liver

function, jaundice, gallstones , deteriorating renal
function.
SCA and Iron deficiency anemia can co-exist.
Iron overload less common usually in those received
multiple blood transfusions
Typically, serum homocysteine levels are elevated “ low
vitamin B12 concentrations”
Medical management
Monthly transfusions – stops body producing sickle cells / normalize RBC
count.
and drug hydroxyurea- increase production of healthy fetal hemoglobin ,
reducing hospitalization.
◦ Lowers WBC count – need for monitoring and regular blood tests.
Other treatments for pain relief “oxygen therapy
 Sickle Cell Anemia

Protein-energy malnutrition common; may have poor intake

“pain” and increased energy needs “increased metabolic rate”.
Promote foods high in copper, zinc and folate as needs are
increased due to constant replacement of erythrocytes
Zinc supplements may be useful – increase oxygen affinity of
normal /sickle cells
Folate 400-600 mcg daily –ioncreased requirements because
of the increased RBC to replace cells being destroyed
 Sickle Cell Anemia

A multivitamin& mineral with 50%-150% of RDA for folate,

zinc, copper and not iron .
Increasing fluid intake and limiting high sodium foods and
drinks – vasocclusive events
Be careful not to overdo iron in diet or supplements; iron
stores are often high due to frequent transfusions; avoid iron
rich foods, alcohol, and ascorbic acid which enhance iron
absorption.
However iron deficiency might be present , assessed and diet
should be assessed regularly.
 Sports Anemia “Hypochromic
Microcytic Transient Anemia”
Increased RBC destruction, decreased hemoglobin serum
iron and ferritin conc.
Transient—usually thought in athletes who are runners;
from compression of RBCs in feet until they burst, releasing
hemoglobin
Now thought to be physiologic (transient problem of blood
volume and dilution
Check lab values
◦ diagnosed based on a complete blood cell count with
differential, serum ferritin level, serum iron level, TIBC,
and percent saturation of iron-binding capacity.
 Sports Anemia “Hypochromic
Microcytic Transient Anemia”
proper diet:
nutrient and iron-rich foods
adequate protein; and avoiding tea, coffee, antacids, H2-
blockers, and tetracycline, all of which inhibit iron absorption.
No athlete should take iron supplements unless true iron
deficiency
Athletes who are female, vegetarian, involved in endurance
sports, or entering a growth spurt are at risk for iron
deficiency anemia and therefore should undergo periodic monitoring
 Thalassemia
Severe inherited anemia affecting mostly people of Mediterranean extraction

Microcytic, hypochromic, and short-lived RBCs resulting from defective hemoglobin synthesis

Defective globin formation in hemoglobin leads to increased blood volume, splenomegaly, bone marrow
expansion, facial deformities, osteomalacia, bone changes

Iron accumulation – dysfunction in heart, liver and endocrine glands.

Iron buildup due to transfusions requires chelation therapy to remove excess iron
 Thalassemia
The diet should be high in protein, B vitamins, especially folic acid, and zinc.
Multivitamin and mineral supplements that contain amounts of iron and
vitamin C above the RDA should be avoided.
Increased calcium intake may be required in some patients because of bone
formation issues.
Patients should stay well hydrated.
Medical and Nutritional
Management of Anemia
It is important to be familiar with the etiology and treatment of
nutritional and non-nutritional anemias
Many non-nutritional anemias have nutritional implications
It is critical to DIAGNOSE before treating anemias with nutritional or
non-nutritional therapies