NUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #225
Carol Rees Parrish, MS, RDN, Series Editor
16 PRACTICAL GASTROENTEROLOGY • SEPTEMBER 2022
NUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #225
Micronutrients and Gastric Bypass –
What We Have Learned
Abby Bellows MS, RDN, CNSC Nutrition
Support Specialist UVA Health Charlottesville,
VA Kelly O’Donnell MS, RD, CNSC Nutrition
Support Specialist UVA Health Charlottesville, VA
Bariatric surgery is a leading treatment for severe obesity, yet brings with it the risk for
micronutrient deciencies due to resection of primary absorption sites, reduced intake,
and a number of other factors. Micronutrient deciencies can have serious, sometimes
irreversible consequences if left untreated. Clinician education about signs and symptoms of
deciencies, supplementation guidelines, and recommendations for repletion and monitoring
is paramount in preventing micronutrient deciencies and the resulting complications.
Abby Bellows Kelly O’Donnell
CASE STUDY
A
60-year-old male was admitted to our hospital
for gastrostomy tube placement into his
remnant stomach 14 months after Roux-en-Y
gastric bypass (RYGB) due to persistent poor intake,
weakness, and a nearly 200-pound weight loss. On
average, he consumed less than 500 calories and
20 grams of protein per day and was non-adherent
with his vitamin and mineral regimen. Since his
surgery, he had become wheelchair-bound because
of lower extremity weakness, ataxia, neuropathy,
and regular falls. Prior to gastric bypass surgery, he
walked independently except on uneven surfaces
which required a cane. Given these symptoms
and his altered anatomy, several micronutrient
deciencies were suspected including vitamin
B12, copper, vitamin E, thiamine, vitamin B6,
and niacin.
INTRODUCTION
The prevalence of obesity in adults in the United
States was 42.4% in 2017-2018, a notable increase
from 30.5% in 1999-2000. Obesity is associated
with a number of comorbid medical conditions
including heart disease, type 2 diabetes, and stroke,
and places a signicant burden on the healthcare
system.
1
Bariatric surgery is recognized as the
most effective treatment for severe obesity.
2
The
number of bariatric surgeries performed each year
rises with the increasing prevalence of obesity. In
2019, it is estimated that 256,000 bariatric surgeries
were performed in the U.S., 17.8% of which were
RYGB.
3
It is well established that RYGB places
NUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #225
Micronutrients and Gastric Bypass – What We Have Learned
PRACTICAL GASTROENTEROLOGY • SEPTEMBER 2022 17
NUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #225
paralysis, and mood disturbance, and if left
untreated can result in severe, irreversible
neurological complications.
7,8,10
Other signs and
symptoms of deciency include megaloblastic
and macrocytic anemias, fatigue, numbness and
paresthesia in extremities, ataxia, magenta “beefy
red” tongue, glossitis, pale skin, and slightly icteric
skin and eyes.
11
In the rst year postoperatively, screening
for B12 deciency is recommended every three
months according to the CPGs, followed by
yearly screening thereafter or as indicated.
11,12
Recommended laboratory assessments are serum
vitamin B12 and, in some cases, methylmalonic
acid (MMA).
10,11,13
Serum B12 may be falsely
elevated in the setting of alcoholism, liver disease,
and cancer.
13
Deciency may be present even
when serum B12 is normal, since serum levels are
maintained at the expense of tissue stores.
8,11
MMA
should be considered in patients with normal or
low-normal vitamin B12, macrocytosis, or clinical
suspicion for B12 deciency.
13
Elevated MMA can
be indicative of B12 deciency, however, MMA
levels are also increased with renal disease, so
should therefore be interpreted with caution.
8,11
The CPGs recommend routine B12
patients at risk for micronutrient deciencies, and
many patients are noncompliant with recommended
vitamin/mineral supplementation.
4-6
Clinicians
must be aware of recommendations for screening,
assessment, and treatment of micronutrient
deciencies in RYGB patients. A summary of
specic recommendations can be found in tables
1-4. Acute inammation may affect laboratory
data for some micronutrients, details of which
are included in the tables for each respective
nutrient. Updated Clinical Practice Guidelines were
published in 2019 and will hereafter be referred to
as “CPGs.”
12
Vitamin B12 (Cyanocobalamin)
Vitamin B12 (B12) is necessary for neurological
function, growth and development of red blood
cells, and DNA synthesis.
7
A signicant number
of patients develop B12 deciency after RYGB
as a result of impaired absorption, decreased oral
intake, lack of intrinsic factor, and reduced gastric
acid.
8,9
Use of certain medications, including
metformin, proton pump inhibitors, and H2
receptor antagonists, may increase the risk of B12
deciency.
7
B12 deciency is associated with dementia,
Table 1. Routine Supplementation Guidelines
Nutrient Routine Supplementation Guideline
Multivitamin w/ minerals
• Twice daily
12
Vitamin B12
• Oral: 350-1000 mcg daily
OR
• Intramuscular: 1000 mcg monthly
12
• *Currently, there are insufficient data to recommend nasal or sublingual
B12 supplementation after RYGB
13,56
Vitamin D
• 3000 IU vitamin D3 daily until serum 25(OH)-vitamin D is >30 ng/mL
• Ongoing dosage should then be based on serum levels
• Note: vitamin D3 is preferred over vitamin D2
12
Calcium
• 1200-1500 mg calcium daily in divided doses
12
Thiamine
• 12 mg daily (Grade C)
11
Iron
• Menstruating females: 45-60 mg daily of elemental iron (includes iron
from vitamin/mineral supplements)
• Take in divided doses separate from calcium, acid-reducing medication,
foods high in phytates or polyphenols
12
18 PRACTICAL GASTROENTEROLOGY • SEPTEMBER 2022
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Micronutrients and Gastric Bypass – What We Have Learned
Table 2. Water-Soluble Vitamins
Nutrient Signs/Symptoms of Deficiency Lab Assessment Various Guidelines for Repletion of Deficiency
B12
• Megaloblastic anemia, fatigue, numbness and
paresthesia in extremities, ataxia, altered mental
status, dementia, paralysis, mood disturbance
• Magenta “beefy red” tongue, glossitis, pale skin,
slightly icteric skin and eyes
7,8,10,11
• Serum B12
7
• Methylmalonic acid (MMA)
7,8,11,13
• Note: serum levels of B12 are maintained
at expense of tissue stores, and therefore
deficiency may be present even when
serum B12 appears normal
8
• Serum levels may be elevated in acute
inflammation, liver disease, malignancies,
or other disease states
57,58
• 1000 mcg daily until normal serum B12 is achieved (recheck every 3-6 months)
• Then return to maintenance supplementation
12
B6
(Pyridoxine)
• Seborrheic dermatitis, glossitis, lip and angular
cheilitis, impaired immune function, peripheral
neuropathy, seizures, hypochromic microcytic
anemia
• Pellagra-like symptoms are possible in severe
cases
10,31,32
• Plasma, erythrocyte, or urinary pyridoxal-
5-phosphate
10
• Decreased plasma levels may be seen in
acute inflammation
59
• 100 mg oral pyridoxine daily
32
• 25-600 mg daily depending on severity of symptoms
10
• Consider IV supplementation for patients with severe symptoms (i.e., seizures)
10
Caution with long term high dose* supplementation:
Associated with sensory neuropathies and movement disorders
10
*High dose supplementation not clearly defined
• “Toxic dose” is defined as 1000 mg/day and is associated with sensory neuropathy
33,34
• Tolerable Upper Intake Level is 100 mg/day for adults
60
• Use caution with higher doses or prolonged supplementation
33,61
• Higher doses below 1000 mg/day may have adverse effects, including indigestion, nausea, and
photosensitivity
33
B2
(Riboflavin)
• Angular and lip cheilitis, glossitis, nasolabial
dermatitis, scrotal and vulvar eczema, anemia,
peripheral neuropathy
31,32
• Preferred: Erythrocyte glutathione
reductase activity coefficient (EGRAC);
cannot be used in patients with glucose-
6-phosphate-dehydrogenase deficiency
• Serum riboflavin (should be performed
after an overnight 12-hour fast)
10
• No consensus
10
• 10-60 mg oral vitamin B2 daily
32
Caution with high dose supplementation (>100 mg/day):
Chronic use may lead to damage of the ocular lens proteins and the retina
10
B3
(Niacin)
• Pellagra
• 4 D’s: dermatitis, dementia, diarrhea, death
• Weakness, fatigue, depression,
hyperpigmentation of sun-exposed areas of skin
(“glove,” “boot,” and “Casal’s necklace”)
10,31
• Urinary N1-methylniconatinamide and
N1-methyl-2-pyridone-5-carboxamide
10
• 250-500 mg oral nicotinamide daily
31
• 500 mg oral nicotinic acid daily
32
• 100-300 mg subcutaneous niacinamide in 3 doses for patients with pellagra
10
Vitamin C
• Scurvy
• Perifollicular hemorrhages, ecchymosis,
petechiae, xerosis, poor wound healing,
corkscrew or swan-neck hairs, bleeding gums,
fatigue, malaise, weakness
32,36
• Treat if deficiency is suspected
• Serum or leukocyte vitamin C
10
• Plasma levels may be decreased in acute
inflammation, particularly in sepsis and
after cardiac arrest
59,62,63
• 1-2 g vitamin C daily for 2-3 days, followed by 500 mg daily for 1 week, followed by 100 mg daily for
1-3 months
31
• 1-2 g daily
64
• 300 mg daily for 3 months
10
• 2 g daily for 3 days followed by 500 mg daily for 1 week, followed by 100 mg daily for 3 months
10
Note: absorption decreases with doses >1g/day
10
B1
(Thiamine)
• Ataxia, confusion, nystagmus, ophthalmoplegia,
peripheral neuropathy, weakness usually in
lower extremity
21
• Treat if deficiency is suspected; if
levels are checked, use whole blood or
erythrocyte
22,23
• Dose is based on route and severity of symptoms:
100-500 mg 2-3x daily
11,12
NUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #225
PRACTICAL GASTROENTEROLOGY • SEPTEMBER 2022 19
Micronutrients and Gastric Bypass – What We Have Learned
Table 2. Water-Soluble Vitamins
Nutrient Signs/Symptoms of Deficiency Lab Assessment Various Guidelines for Repletion of Deficiency
B12
• Megaloblastic anemia, fatigue, numbness and
paresthesia in extremities, ataxia, altered mental
status, dementia, paralysis, mood disturbance
• Magenta “beefy red” tongue, glossitis, pale skin,
slightly icteric skin and eyes
7,8,10,11
• Serum B12
7
• Methylmalonic acid (MMA)
7,8,11,13
• Note: serum levels of B12 are maintained
at expense of tissue stores, and therefore
deficiency may be present even when
serum B12 appears normal
8
• Serum levels may be elevated in acute
inflammation, liver disease, malignancies,
or other disease states
57,58
• 1000 mcg daily until normal serum B12 is achieved (recheck every 3-6 months)
• Then return to maintenance supplementation
12
B6
(Pyridoxine)
• Seborrheic dermatitis, glossitis, lip and angular
cheilitis, impaired immune function, peripheral
neuropathy, seizures, hypochromic microcytic
anemia
• Pellagra-like symptoms are possible in severe
cases
10,31,32
• Plasma, erythrocyte, or urinary pyridoxal-
5-phosphate
10
• Decreased plasma levels may be seen in
acute inflammation
59
• 100 mg oral pyridoxine daily
32
• 25-600 mg daily depending on severity of symptoms
10
• Consider IV supplementation for patients with severe symptoms (i.e., seizures)
10
Caution with long term high dose* supplementation:
Associated with sensory neuropathies and movement disorders
10
*High dose supplementation not clearly defined
• “Toxic dose” is defined as 1000 mg/day and is associated with sensory neuropathy
33,34
• Tolerable Upper Intake Level is 100 mg/day for adults
60
• Use caution with higher doses or prolonged supplementation
33,61
• Higher doses below 1000 mg/day may have adverse effects, including indigestion, nausea, and
photosensitivity
33
B2
(Riboflavin)
• Angular and lip cheilitis, glossitis, nasolabial
dermatitis, scrotal and vulvar eczema, anemia,
peripheral neuropathy
31,32
• Preferred: Erythrocyte glutathione
reductase activity coefficient (EGRAC);
cannot be used in patients with glucose-
6-phosphate-dehydrogenase deficiency
• Serum riboflavin (should be performed
after an overnight 12-hour fast)
10
• No consensus
10
• 10-60 mg oral vitamin B2 daily
32
Caution with high dose supplementation (>100 mg/day):
Chronic use may lead to damage of the ocular lens proteins and the retina
10
B3
(Niacin)
• Pellagra
• 4 D’s: dermatitis, dementia, diarrhea, death
• Weakness, fatigue, depression,
hyperpigmentation of sun-exposed areas of skin
(“glove,” “boot,” and “Casal’s necklace”)
10,31
• Urinary N1-methylniconatinamide and
N1-methyl-2-pyridone-5-carboxamide
10
• 250-500 mg oral nicotinamide daily
31
• 500 mg oral nicotinic acid daily
32
• 100-300 mg subcutaneous niacinamide in 3 doses for patients with pellagra
10
Vitamin C
• Scurvy
• Perifollicular hemorrhages, ecchymosis,
petechiae, xerosis, poor wound healing,
corkscrew or swan-neck hairs, bleeding gums,
fatigue, malaise, weakness
32,36
• Treat if deficiency is suspected
• Serum or leukocyte vitamin C
10
• Plasma levels may be decreased in acute
inflammation, particularly in sepsis and
after cardiac arrest
59,62,63
• 1-2 g vitamin C daily for 2-3 days, followed by 500 mg daily for 1 week, followed by 100 mg daily for
1-3 months
31
• 1-2 g daily
64
• 300 mg daily for 3 months
10
• 2 g daily for 3 days followed by 500 mg daily for 1 week, followed by 100 mg daily for 3 months
10
Note: absorption decreases with doses >1g/day
10
B1
(Thiamine)
• Ataxia, confusion, nystagmus, ophthalmoplegia,
peripheral neuropathy, weakness usually in
lower extremity
21
• Treat if deficiency is suspected; if
levels are checked, use whole blood or
erythrocyte
22,23
• Dose is based on route and severity of symptoms:
100-500 mg 2-3x daily
11,12
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Micronutrients and Gastric Bypass – What We Have Learned
NUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #225
to raise 25(OH)-vitamin D beyond 30 ng/mL in
RYGB patients.
14,15
Higher doses have proven
effective in some patients, but others may require
even greater supplementation to maintain optimal
serum levels.
15,17
The CPGs recommend routine
supplementation and continued monitoring of
vitamin D status.
12
Ongoing dosage should be based
on serum levels. Vitamin D3 (cholecalciferol) is the
preferred form of vitamin D for supplementation
due to its higher potency, according to the CPGs.
12
Short term, high dose supplementation is not
likely to be a comprehensive solution for vitamin
D deciency in RYGB patients; they will likely
need supplemental vitamin D in the long term to
maintain optimal serum levels.
Vitamin B1 (Thiamine)
Thiamine is a water-soluble vitamin essential for
glucose metabolism, ATP production, and plays
a role in maintaining the integrity of the nervous
system. When oral intake is reduced, thiamine
stores may be consumed quickly (9 to 18 days).
18
Thiamine deciency is a clinical diagnosis and if
undetected and untreated, may result in Wernicke-
Korsakoff Syndrome.
19,20
Recognizing risk factors and early signs and
symptoms are the keys to detecting thiamine
deciency. RYGB patients with persistent vomiting
are at risk for thiamine deciency since vomiting
precludes adequate intake. In addition, the primary
sites of absorption which include the duodenum
and rst part of the jejunum are bypassed. These
factors, combined with limited storage, may quickly
lead to thiamine deciency after surgery. Rapid
weight loss and non-compliance with vitamins are
also contributing factors.
18,21
Wernicke’s Encephalopathy (WE) is a
neurological disorder caused by thiamine
deciency. Hallmark symptoms include the triad
of mental status changes, ataxia, and eye movement
disorders. In a recent study of WE after bariatric
surgery, ataxia was the most common characteristic
found in patients.
21
The full triad of symptoms
may be seen in an estimated 20-50% of patients
with WE.
21
In addition, patients may experience
paresthesias, peripheral neuropathy, and weakness,
usually in the lower extremities.
Thiamine diphosphate, or thiamine
(continued on page 26)
supplementation for all RYGB patients.
12
Patients with deciency should receive
additional supplementation.
12
The need for B12
supplementation beyond what is contained in a
standard multivitamin is addressed in a systematic
review of the literature by Mahawar et al., which
showed that oral doses up to 15 mcg daily were
insufcient to prevent deciency. Doses of 600
mcg daily proved superior to 350 mcg daily,
and 1000 mcg daily was sufcient to prevent
deciency in most patients.
9
Concerning the route
of supplementation, there is evidence to suggest
that vitamin B12 sufciency can be maintained
with oral supplementation in RYGB patients.
8
Regardless of route, it is important to monitor
B12 status as vitamin/mineral non-adherence is
common.
Vitamin D
Vitamin D is a steroid hormone and nutrient which
is involved in bone metabolism as well as a number
of other body processes.
14
Humans primarily
obtain vitamin D through exposure to UVB light,
in addition to dietary intake.
14,15
A review of the
literature by Peterson et al. demonstrates that up
to 90% of RYGB patients are vitamin D decient
(<20 ng/mL) in the pre-operative period.
14
Many
studies indicate ongoing vitamin D deciency
after bariatric surgery, however, some have
demonstrated improvement in vitamin D status in
the post-operative period purported to result from
release of sequestered vitamin D from adipose
tissue as patients lose weight. However, this is
often followed by high prevalence of deciency
or insufciency.
14-16
RYGB patients may have decreased absorption
of vitamin D due to decreased surface area of the
small intestine as well as altered mixing with
pancreatic secretions and bile. Additionally, risk
of vitamin D deciency may be increased as a
result of sequestration of vitamin D in adipose
tissue and lack of sun exposure.
15
Vitamin D deciency can result in increased risk
of osteopenia and osteoporosis, muscle weakness,
falls, and generalized pain and discomfort.
15
Symptoms of deciency may also include
hypocalcemia, tetany, tingling, or cramping.
11
Literature shows that dosages below 800 IU
(20 mcg) of vitamin D3 daily are not sufcient
26 PRACTICAL GASTROENTEROLOGY • SEPTEMBER 2022
NUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #225
Micronutrients and Gastric Bypass – What We Have Learned
patients in the pre- and post-operative periods.
11,12,28
However, RYGB patients may be at increased
risk for deciency due to resection of primary
absorption sites, altered mixing with pancreatic and
biliary secretions, steatorrhea, or small intestinal
bacterial overgrowth.
28
In a systematic review of
the literature, Sherf-Dagan found deciency rates
of up to 65.7% in 1-5 years after bariatric surgery.
28
Signs and symptoms of vitamin E deciency
include spinocerebellar ataxia, peripheral
neuropathy, gait disturbances, decreased sensation,
ophthalmologic disorders, nystagmus, impaired
immune response, and hemolytic anemia.
11,28,29
The CPGs recommend supplementation for all
bariatric surgery patients, which can be attained
with a multivitamin.
12
Most supplements provide
alpha-tocopherol, which is the most common
form of vitamin E in human tissues and is the
most biologically active form.
28,29
Additional
supplementation may be needed to replete
deciency, however therapeutic dosing is not
clearly dened.
11,12,28
Prompt supplementation
of vitamin E can stop progression of, or even
normalize, neuromuscular decits resulting from
deciency.
29
High dose vitamin E supplementation
(>1000 mg/day) may increase risk for competition
with vitamin K and has been associated with
hemorrhage.
10,30
Vitamin B6 (Pyridoxine)
Vitamin B6 participates in protein and carbohydrate
metabolism, gluconeogenesis, and neurotransmitter
synthesis.
31,32
Factors that may increase the risk
for deciency are alcoholism and use of certain
medications, including isonizid (antituberculosis),
hydralazine, penicillamine, contraceptives, levo/
carbidopa, and antiepileptic medications.
10,31,32
Signs and symptoms of B6 deciency include
seborrheic dermatitis, glossitis, lip and angular
cheilitis, impaired immune function, peripheral
neuropathy, seizures, and hypochromic microcytic
anemia.
10,31,32
Pellagra-like symptoms are possible
in severe cases, since B6 is necessary for synthesis
of nicotinic acid (see Niacin section).
31,32
Treatment of deciency varies within the
literature depending on the severity of symptoms.
IV supplementation should be considered for
patients with severe symptoms, such as seizure.
10
Long-term high dose supplementation is associated
pyrophosphate (TPP), is the biologically active
form of thiamine. Because TPP is found in
erythrocytes and accounts for 90% of thiamine in
whole blood, the use of whole blood or erythrocytes
to measure thiamine stores is the most sensitive and
specic method for testing.
22,23
However, given the
long turnaround time for lab assays and the acute
urgency to treat suspected thiamine deciency,
clinical suspicion and awareness of risk factors
should be used to diagnose and treat patients. In
addition, there is no thiamine level that correlates
with the diagnosis of WE.
The American Society for Metabolic and
Bariatric Surgery (ASMBS) treatment for thiamine
deciency depends on the route and severity of
symptoms. There is a paucity of scientic data to
support recommendations for treatment.
12
Vitamin A
Vitamin A is involved in cell growth and
development, immune function, vision, and
functions as an antioxidant against free radicals.
24-26
The prevalence of deciency in the rst 4 years
post-RYGB is up to 70%.
12
Deciency commonly
presents as night blindness and can result in
complete blindness if left untreated.
10,12,24
In fact,
vitamin A deciency is the leading preventable
cause of blindness.
24
Patients decient in vitamin A
may also exhibit Bitot’s spots, hyperkeratinization
of the skin, and poor wound healing.
11,24
Risk
factors for vitamin A deciency associated with
RYGB are decreased intestinal surface area for
absorption, decreased overall food intake, and
low fat diet in the post-operative period.
26
Zinc
deciency, alcohol ingestion, and cholestyramine
use can impair vitamin A absorption.
24
The CPGs recommend routine supplementation
of 5,000-10,000 IU vitamin A daily to prevent
deciency after RYGB, which can be attained with
a multivitamin.
12,27
It is noteworthy that toxicity can
occur with high-dose or chronic supplementation
of vitamin A.
10
Vitamin E
Vitamin E functions as an antioxidant and plays
important roles in neurological health, specically
in the central nervous system.
28,29
Vitamin E
deciency is uncommon in bariatric surgery
(continued from page 20)
NUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #225
PRACTICAL GASTROENTEROLOGY • SEPTEMBER 2022 27
Micronutrients and Gastric Bypass – What We Have Learned
with sensory neuropathies and movement disorders,
among other symptoms, and should be used with
caution.
10
“Toxic dose” is dened as 1000 mg/day,
however there are case reports of neuropathy with
lower doses.
33,34
The Tolerable Upper Intake Level
for vitamin B6 is 100 mg/day for adults.
Vitamin B2 (Riboflavin)
Vitamin B2 is involved in numerous
reduction-oxidation reactions as well as the
conversion of pyridoxine phosphate to vitamin
B6.
31,32
The primary absorption site is the proximal
small intestine, putting RYGB patients at risk for
deciency.
32
Alcoholism and diets low in meat and
dairy can put patients at greater risk.
31
Symptoms
of deciency include angular and lip cheilitis,
glossitis, nasolabial dermatitis, scrotal and vulvar
eczema, anemia, and peripheral neuropathy.
31,32
The
Table 3. Fat-Soluble Vitamins
Nutrient Signs and Symptoms
of Deficiency
Lab Assessment Various Guidelines for Repletion
of Deficiency
Vitamin D
• Osteopenia,
osteoporosis
• Muscle weakness,
falls, generalized
pain and discomfort,
hypocalcemia, tetany,
tingling, cramping
11,15
• 25(OH)-vitamin D
12
• Decreased plasma
concentrations can be seen
in acute inflammation or
stress
59,63,65,66
• 3000-6000 IU vitamin D3 daily
OR
• 50,000 IU vitamin D2 1-3x weekly
12
Vitamin A
• Night blindness,
xerophthalmia,
Bitot’s spots
• Hyperkeratinization
of skin, poor wound
healing
10-12,24
• Plasma retinol and
carotenoid
10
• Decreased plasma
concentrations of vitamin
A (retinol) may be seen in
infection, trauma, critical
illness, inflammation, or
acute stress
59,62,63,67,68
• Retinol binding protein
(RBP) is a negative acute
phase protein
67
• Without corneal changes: 10,000-
25,000 IU daily orally
• With corneal changes: 50,000-
100,000 IU IM for 3 days, followed
by 50,000 IU IM daily for 2 weeks
12
Caution with high dose
supplementation:
Toxicity can occur with long-term use
or with single dose >660,000 IU
12
Vitamin E
• Spinocerebellar ataxia,
peripheral neuropathy,
gait disturbances,
decreased sensation,
ophthalmologic
disorders, nystagmus,
impaired immune
response, hemolytic
anemia
11,28,29
• Serum alpha-tocopherol
when serum lipids are
normal
• Adjust for serum
lipids in patients with
hyperlipidemia (serum
alpha-tocopherol divided by
total lipids)
10-12
• Decreased plasma
concentrations may be
seen in acute stress,
however this decrease
may not be observed when
alpha-tocopherol levels are
adjusted for changes in
plasma lipids
59,62,63
• Optimal dose not clearly
defined
11,12,28
• 100-400 IU/d recommended
12
Caution with high dose
supplementation (>1000 mg/d):
May compete with vitamin K for
absorption; risk for hemorrhage
10,30
28 PRACTICAL GASTROENTEROLOGY • SEPTEMBER 2022
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NUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #225
clinical presentation of B2 deciency may mimic
that of B3 or B6 deciencies due to its role in their
metabolism.
31
Supplementation recommendations
vary, and there is limited data.
31,32
Caution should
be used with long term supplementation at doses
>100 mg/day due to potential effects on the ocular
lens proteins and retina.
10
Vitamin B3 (Niacin)
Vitamin B3 has essential roles in metabolism
including ATP synthesis and glycolysis.
31
In a study
by Ledoux et al. (2020), B3 deciency was observed
in 13.1% and 19.8% of patients within 1 year and
> 3 years, respectively, after RYGB.
35
The clinical
manifestation of deciency is pellagra, which is
characterized by dermatitis, dementia, diarrhea, and
potentially death.
10,31
Early symptoms of deciency
include weakness, fatigue, and depression. Physical
exam ndings may resemble sunburn on the face,
neck, and dorsal extremities, hyperpigmented areas
on the extremities known as the “glove” and “boot”
of pellagra, or hyperpigmented areas on the neck
known as Casal’s necklace.
31
Additional risk factors
for deciency include alcoholism, use of isoniazid,
azathioprine, or 6-mercaptopurine.
31
Vitamin C (Ascorbic Acid)
Vitamin C functions as an antioxidant, supports
osteoblast formation in bones and teeth, and is
essential for the formation of collagen.
31,36,37
It
is absorbed in the upper third of the intestine,
and deciency has been observed in the RYGB
population in both the pre- and post-operative
Table 4. Minerals
Nutrient Signs and Symptoms
of Deficiency
Lab Assessment Various Guidelines for
Repletion of Deficiency
Copper
• Peripheral
neuropathy,
myelopathy, ataxia,
muscle weakness,
anemia, neutropenia,
optic neuropathy
42-45
• Serum copper and/or
ceruloplasmin (positive
acute phase reactants)
• MRI-showing
increased T2 signal in
the posterior dorsal
column of the spinal
cord
40,42
• Dose is based on route and severity
of symptoms: 3-8 mg/d oral; 2-4
mg/d IV
11,12,40,42
• 8 mg oral x 1 week, 6 mg for second
week, 4 mg for third week, 2 mg
thereafter; if symptoms persist, use 2
mg IV over 2 hours for 5 days
41
Zinc
• Alopecia, taste
changes, white
spots on the
nails, dermatitis,
skin plaques and
diarrhea
48
• Plasma or serum levels
(levels may not reflect
cellular zinc due to tight
homeostatic control)
10,49
• 2-3 mg/kg/d elemental zinc;
IV: 7-10 mg daily
• Monitor copper levels
10,50-53
Caution with high dose
supplementation: May cause nausea,
vomiting, and gastric irritation
10,50-53
Iron
• Microcytic anemia,
fatigue, dyspnea,
spoon-shaped nails
10
• Microcytic,
hypochromic anemia
(not specific for iron
deficiency)
• Iron studies which may
include serum iron*,
TIBC, transferrin*,
transferrin saturation
and serum ferritin**
• 100-200 mg elemental iron up to 300
mg 2-3 times daily
10,12
• Adding a source of vitamin C may
improve iron absorption
• Consider taking single dose iron on
alternate days vs daily or twice daily
55
• Parenteral iron if there is a lack of
response to oral therapy; monitor
patient for anaphylactic reaction
*May decrease during acute phase response
**May increase during acute phase response
10
(continued on page 30)
30 PRACTICAL GASTROENTEROLOGY • SEPTEMBER 2022
NUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #225
Micronutrients and Gastric Bypass – What We Have Learned
periods.
32,35,38
Patients may be at increased risk
for deciency in cases of alcoholism, ulcerative
colitis, Crohn’s disease, or dialysis. Smoking also
increases risk for deciency due to decreased
intestinal absorption and increased catabolism.
31,32
Vitamin C deciency in its most severe form is
scurvy, which is characterized by perifollicular
hemorrhages, ecchymosis, petechiae, xerosis, poor
wound healing, corkscrew hairs, swan-neck hairs,
bleeding gums, fatigue, malaise, and weakness.
32,36
If left untreated, vitamin C deciency can be fatal,
therefore supplementation should be started if there
is clinical suspicion for deciency rather than
waiting for a lab result to return.
37
Upon initiation
of therapeutic supplementation, symptoms are
expected to resolve quickly, some within the rst
24 hours and others taking weeks to months.
31,37
It should be noted that high dose vitamin C
supplementation can be associated with diarrhea,
other GI upset, or falsely elevated blood glucose
readings on point-of-care glucose monitors.
10,31,39
Absorption of vitamin C decreases with doses over
1 g/day.
10
Copper
Copper is an essential trace element that plays a role
in neurotransmission, hematopoiesis, hemoglobin
synthesis, and the formation of connective tissue. It
is primarily absorbed in the stomach and proximal
duodenum, placing a gastric bypass patient at risk
for deciency since these sites are reduced or
bypassed after surgery.
40
Kumar reported on 34
cases of symptomatic copper deciency occurring
an average of 9 years after surgery with 97% of
the cases non-compliant with taking multivitamins
and minerals.
41
Symptoms of copper deciency include
neurological decits such as peripheral neuropathy,
ataxia, and muscle weakness. Myelopathy and
myeloneuropathy seen with copper deciency
closely resemble vitamin B12 deciency. Symptoms
may also include anemia and/or neutropenia. Optic
neuropathy and blindness as a result of copper
deciency have also been reported.
42-45
To diagnose a deciency, serum copper
levels are used. Another marker often used is
ceruloplasmin, a protein that transports 80-95%
of copper. It is, however, an acute phase protein that
increases during inammation which in turn leads
to an elevated serum copper level. To diagnose
deciency, one author recommends using serum
copper, ceruloplasmin < 20 mg/dL, and elevated
C-reactive protein.
42
An MRI showing increased T2
signal in the posterior dorsal column of the spinal
cord may enhance lab data when determining a
diagnosis.
40
Other than case studies, little scientic evidence
is available on the route, amount, or timing of
copper supplementation. Supplementation halts
the progression of neurological decits, but may
not reverse them. It usually takes 4-12 weeks for
hematologic consequences of copper deciency to
resolve.
40,42,46
Several strategies and guidelines for
replacement of copper are available.
41,42,47
Copper
levels should be checked periodically after levels
return to normal and supplementation stops since
cases of relapse have been reported.
12
Zinc
Zinc is a mineral that plays a role in DNA and
protein synthesis, immune function, wound
healing, and more than 300 enzyme systems. It is
primarily absorbed in the duodenum and proximal
jejunum which may lead to a deciency since these
areas are bypassed after RYGB. Poor intake and
non-compliance with vitamins and minerals may
also contribute. Symptoms of deciency include
alopecia, taste changes, white spots on the nails,
dermatitis, skin plaques and diarrhea.
48
In a recent summary, only 6 cases of symptomatic
zinc deciency were found in the literature. On
average, patients became symptomatic 6 years
after surgery, 67% were female, and all had a skin
rash. Information on vitamin compliance was
available for 2 patients; one had stopped taking
PRACTICAL
GASTROENTEROLOGY
4
6
Years
E
s
t
a
b
l
i
s
h
e
d
1
9
7
7
(continued from page 28)
NUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #225
PRACTICAL GASTROENTEROLOGY • SEPTEMBER 2022 31
Micronutrients and Gastric Bypass – What We Have Learned
her supplement, and the other was compliant.
48
Since it is a component of various proteins
and nucleic acids, zinc levels are difcult to
measure. Plasma or serum levels are often used,
but levels do not necessarily reect cellular zinc
due to tight homeostatic control. Also, clinical
signs can be present in the absence of abnormal
laboratory indices. Some suggest pairing clinical
correlation with lab values and risk factors to aid
in the diagnosis of a deciency.
10,49
ASMBS guidelines do not issue a
recommendation due to insufcient evidence,
however, they advise caution when repleting
zinc as it can induce a copper deciency over
time. Excess amounts of enteral zinc may cause
nausea, vomiting, and gastric irritation. Skin
lesions usually improve within days to weeks of
supplementation.
10,50-53
A Word about Iron
Iron deciency is the leading cause of anemia
after RYGB. Factors contributing to this include
decreased hydrochloric acid production in the
gastric pouch, decreased meat consumption, and
bypassing the duodenum and jejunum which are
the primary sites of absorption.
54
Iron deciency
may occur despite routine supplementation and
should be monitored within 3 months after surgery
followed by every 3 to 6 months for the rst
year and then annually thereafter unless clinical
signs and symptoms of deciency are present.
12
Adherence to supplementation may be affected
by side effects which can include constipation,
nausea, vomiting and a metallic taste.
10
Many oral
iron preparations are available, but none have been
shown superior to ferrous sulfate. A recent article
suggests absorption of oral iron improves when
taken on alternate days in single doses versus daily
or twice daily in healthy women with depleted
iron stores.
55
CASE STUDY CONCLUSION
A serum copper level was drawn and found to
be low at 57 mcg/dL (normal 75-145 mcg/dL).
The patient was anemic, but not neutropenic. He
was treated with 2 mg/d oral copper gluconate. He
also received 0.5 mg of copper in his multivitamin
and 1.92 mg in his tube feeding for a total of 4.42
mg/d copper. Copper levels returned to normal 1.5
months after supplementation began. In addition,
the patient did not experience any more falls after
initiation of both copper supplementation and tube
feeding. His ambulation improved to the point that
he was able to walk using a cane, but remained
wheelchair-dependent outside of the home. Copper
levels continued to rise, and supplementation was
discontinued after 7 months as the patient’s ability
to ambulate without falls remained stable. Levels
were checked regularly every 3 months thereafter.
SUMMARY
It is well documented that patients who have
undergone RYGB are at risk for micronutrient
deciencies. There is a paucity of data regarding the
treatment of micronutrient deciencies in the RYGB
population, and most evidence to date comes from
case studies rather than RCTs. Clinicians should
be aware of signs and symptoms of micronutrient
deciencies as they collect a detailed patient
history and perform a physical exam. Adherence
to vitamin and mineral supplementation should be
assessed. It should also be noted that micronutrient
deciencies rarely exist in isolation; if a patient
presents with one deciency, there are likely others.
Lastly, vitamin and mineral supplementation is not
benign and should be monitored and adjusted as
clinically appropriate.
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