Hypoalbuminemia

The Role of Oral Albumin

Supplementation in Elderly
Siti Setiati
 Albumin

• Albumin is the most

abundant protein plasma,
with more than 50% of
plasma protein were made.
• Albumin is synthesized
in the liver, pre-albumin
 pro-albumin  Golgi
apparatus that will change
pro-albumin  albumin 
secreted by hepatocytes

1. Gounden J, Jialal I. Hypoalbumenia. 2015

2. Kuzuya M, Izawa S, Enoki H, et al. Is serum albumin a good marker for malnutrition in the physically
impaired elderly? Clin Nutr 2007;26:84–90.
Exogenous Factors Influencing the Albumin

• Insulin
• Growth Hormone

• Inflammatory mediators: IL-6, IL-1, TNF𝛼

Albumin Roles in the Body

Maintaining oncotic pressures

Have low affinity, thus making albumin a good carrier for:

• Endogenous and exogenous hormone
• Unconjugated bilirubin
• Drugs
• Fatty acids with anti-oxidant properties
Bound with 40% calcium, thyroxine, cortisol, and circulating testosterone

Nutritional status marker and disease severity in patients with chronic condition or critically ill

Gounden J, Jialal I. Hypoalbumenia. 2015

Hypoalbuminemia

The mean normal range of Hypoalbuminemia is when the

albumin is between 35 until 50 g/L albumin is < 35 g/L

Soeters PB,, et al. Hypoalbuminemia: Pathogenesis and Clinical Significance. ournal of Parenteral and Enteral Nutrition. 2019;43(2):181-93
Hypoalbuminemia Profile in RSCM (2017)
Perubahan Kadar Albumin Pasca
Jumlah Pasien di RSCM Transfusi di RSCM

1679
4611
1387

2667

55

>2,5 mg/dL 2,5 mg/dL <2,5 mg/dL

Kadar Albumin
<2,5 MG/DL >2,5 MG/DL
Kadar Albumin
 Etiology of Hypoalbuminemia
Decrease Increase Distribution Increase
Synthesis Catabolism Alteration Clearance

• Cirrhosis
• Hemodilution • Renal: Nephrotic
• Malabsorption
syndrome • Infection • Decrease syndrome
• Severe burn
• Nutrition • Sepsis lymphatic
wound
deficiency clearance
(decrease intake)
• Cancer • Increase
• GI Tract:
Enteropathy
• Critically ill transcapillary:
heart failure,
vasculitis,
diabetes
Gatta A, et al. Hypoalbuminemia. Intern Emerg Med. 2012;7(Suppl 3):S193-9.
Hypoalbuminemia Profile in RSCM (2017)
Jumlah Pasien di RSCM
N04.9 - NEPHROTIC SYNDROME,… 48
K74.6 - CIRRHOSIS OF LIVER 49
Z51.1 - CHEMOTHERAPY SESSION FOR… 52
Etiologi Hipoalbuminemia C56 - MALIGNANT NEOPLASM OF… 62
P07.3 - OTHER PRETERM INFANTS 66
Q21.3 - TETRALOGY OF FALLOT 79
E11.5 - DM WITH PERIPHERAL… 83
Q21.0 - VENTRICULAR SEPTAL DEFECT 84
C53.9 - MALIGNANT NEOPLASM OF… 105
P36.9 - BACTERIAL SEPSIS OF… 116
J18.9 - PNEUMONIA, UNSPECIFIED 116
A41.9 - SEPTICAEMIA, UNSPECIFIED 239

0 50 100 150 200 250 300

 • Hypoalbuminemia is a predictor of increased
mortality and morbidity
• Meta-analyses of cohort studies and controlled
Hypoalbuminemia trials in acutely ill patients showed that each
decrease of 10 g litre-1 in plasma albumin
in Surgical or ICU concentration significantly raised the odds of:
Patients • Mortality by 137%
• Morbidity by 89%
• Prolonged ICU by 28%
• Hospital stay by 71%
 2017; retrospective cohort study

The mean length of hospitalization was significantly

longer with mild and marked hypoalbuminemia (7 ± 8
and 9 ± 11 days, respectively) compared with patients
with normal albumin levels on admission (5 ± 7 days; P
< .001 for both).
• In age group more than 60 years old,
the in-hospital mortality for marked
hypoalbuminemia was higher than
mild hypoalbuminemia
• The same result was also found in
mortality at the end of follow-up
(around 3-4 years)
• In addition, the mean ± SD serum
albumin levels were lower with
increased age (P < .001 for all
comparisons).
Hypoalbuminemia Management

• Finding out the main cause of

hypoalbuminemia and treat the main
cause
• Albumin transfusion may be needed in
several condition
 Albumin Infusion Indication
INDICATIONS FOR THE USE OF ALBUMIN
Indications Notes GoR
Paracentesis 5 g or albumin/L ascitic fluid 1C+
Therapeutic Plasmapheresis For exchanges of >20 mL/kg in one session or >20 mL/kg/week in 2C+
more than one session
Spontaneous Bacterial Peritonitis In association with antibiotics 1C+
Heart Surgery Last-choice treatment after crystalloids and non-protein colloids 2C+
Major Surgery Albumin should not be used in the immediate post-operative period 2C+
Only indication for use: serum albumin <2 g/dL after normalisation
of circulatory volume
Cirrhosis of the liver with Generally ineffective, except in patients with serum albumin <2g/dL 2C
refractory ascites
Burns In the case of burns >30% body surface area, after the first 24 hours 2C+

Liumbruno G, et al. Recommendations for the use of albumin and immunoglobulins. Blood Transfus. 2009;7(3):216-34.
 Inappropriate Indication for Albumin Infection
1. Albuminaemia > 2.5 g/dL 2. Chronic hypoalbuminemia in the absence of oedema
and/or acute hypotension

3. Malnutrition 4. Wound Healing

5. Non-haemorrhagic shock 6. Ascites responsive to diuretics

7. Burns, in the first 24 h 8. Protein losing enteropathies and malabsorption

9. Acute or chronic pancreatitis 10. Haemodialysis

11. Cerebral ischaemia

13. Ovarian hyperstimulation syndrome

Liumbruno G, et al. Recommendations for the use of albumin and immunoglobulins. Blood Transfus. 2009;7(3):216-34.
Channa striata / Snakehead Fish /
Ophiocephalus striatus / Ikan Gabus
• Native to east and southeast Asia.
• Occurs mainly in shallow freshwater habitats, typically at
depths of 1-2 m, rarely below 10 meters.
• This species can be found in most types of slow-moving
freshwater habitat, including rivers, lakes, ponds, canals,
creeks, flooded rice paddies, irrigation reservoirs, and
swamps.

https://animaldiversity.org/accounts/Channa_striata/
 Channa striata / Snakehead Fish / Ophiocephalus
striatus / Ikan Gabus

• Predacious, ambush feeding fish that has a carnivorous -

specifically piscivorous - diet.
• Adult Channa hunt on their own, feeding on other adult
fish, and the progeny of those fish. They can also feed
on frogs, snakes, insects, earthworms, tadpoles, birds,
small mammals, and crustaceans.
• Some cultures use snakehead muscle tissue and oils to
heal wounds, prevent scarring, and administer it to
those recovering from surgery or sickness.

https://animaldiversity.org/accounts/Channa_striata/
Nutritional Composition of C. striatus
Intake of 2,5 grams of leucine stimulated
Muscle protein synthesis (MPS)
Nutrient precentage in fresh fish

Zuraini A, et. al. Fish Food Chem 2006;97:674-8.

Mustafa A, et. al. IJSTE 2013;2(4):1-11.

 The Comparison Effectiveness Of Pure Snakehead Fish Extract Therapy
Compare With Human Albumin 20% On Blood Albumin Level and Blood
pH In The Hypoalbuminemic Patient
Thesis by Nugroho

•Design Study: RCT

•Total Subjects: 22 ICU patients (3 days follow-up)

• Intervention group (consumed snakehead fish extract 3x10 gr/day)
• Control group (human albumin 20% IV 1 vial).

•Result:
• Increase in the blood albumin level both groups.
• Decrease in blood pH for both groups.
• The result between these two groups were not significant.
Nugroho AY. The Comparison Effectiveness Of Pure Snakehead Fish Extract Therapy Compare With Human Albumin 20% On Blood Albumin Level and Blood pH In The Hypoalbuminemic Patient. Thesis.
2016.
 The Comparison Effectiveness Of Pure Snakehead Fish Extract Therapy
Compare With Human Albumin 20% On Blood Albumin Level and Blood
pH In The Hypoalbuminemic Patient
Thesis by Nugroho

Nugroho AY. The Comparison Effectiveness Of Pure Snakehead Fish Extract Therapy Compare With Human Albumin 20% On Blood Albumin Level and Blood pH In The Hypoalbuminemic Patient. Thesis.
2016.
 Perbandingan Kenaikan Serum Albumin Setelah Suplementasi Kapsul
Ekstrak Ikan Gabus Dan Putih Telur Ayam Ras Pada Pasien Sepsis Di RS
H.Adam Malik
Thesis by Puteh

•Design Study: RCT

Purpose of this study is to get an alternative for increasing plasma albumin concentration in
patients suffering from sepsis.

Total Subjects: 20 subjects divided into two groups:

• 10 subjects consuming Vipalbumin (3x1000 mg / day)
• 10 subjects consuming egg whites (10 egg whites per day)

Puteh TM. Perbandingan Kenaikan Serum Albumin Setelah Suplementasi Kapsul Ekstrak Ikan Gabus Dan Putih Telur Ayam Ras Pada Pasien Sepsis Di Rs H.Adam Malik. Thesis. 2013
 Perbandingan Kenaikan Serum Albumin Setelah Suplementasi Kapsul
Ekstrak Ikan Gabus Dan Putih Telur Ayam Ras Pada Pasien Sepsis Di RS
H.Adam Malik
Thesis by Puteh

• The mean Albumin in the Vipalbumin Albumin Level

group day-0 was 3,06 and on day-3 was 3.5

3,19. P-value= 0,096. 3

2.5
• The mean Albumin in egg white group 2
was 2,53 and on day-3 was 2,42. P-value 1.5
= 0,201. 1

• The mean albumin difference in 0.5

Vipalbumin group was 0,13 and on the 0

Day-0 Day-3
egg white group was -0,13, p-value was VipAlbumin Egg Whites
0,04
Puteh TM. Perbandingan Kenaikan Serum Albumin Setelah Suplementasi Kapsul Ekstrak Ikan Gabus Dan Putih Telur Ayam Ras Pada Pasien Sepsis Di Rs H.Adam Malik. Thesis. 2013
 The effect of Ophiocephalus striatus supplementation to IGF-1 and
albumin serum in malnourished elderly patients
Roza Mulyana, Siti Setiati

•Design Study: RCT

•Total Subjects:
• 90 malnourished elderly patients: Intervention group (consumed snakehead fish extract 10
gr/day).
• Subjects followed for 2 weeks.

•Result:
• Significant increase in albumin (3.59 vs 3.25), IGF-1 (60.40 vs 45.9).
• Insulin-like growth factor 1 levels are inversely related to inflammatory markers and oxidative stress, and positively
regulated by specific nutrients such as selenium, zinc, magnesium, along with energy and protein.
• Higher level of IGF-1 reduced the inflammation in those patients, which may explain its correlation to the increase of
albumin level.
Mulyana R. The effect of Ophiocephalus striatus supplementation to IGF-1 and albumin serum in malnourished elderly patients. Thesis. Faculty of Medicine Universitas Indonesia. 2017.
 The effect of Ophiocephalus striatus supplementation to IGF-1 and
albumin serum in malnourished elderly patients

IGF-1 (ng/dL) Level Comparison at Baseline Albumin (g/dL) Level Comparison at

and Day-14 Baseline and Day-14
80 3.8
3.59
60.4 3.6
60 47.8 44.2 45.9 3.4 3.25
40 3.2 3.11 3.09
3
20
2.8
0 Day-0 Day-14
Day-0 Day-14
Intervention Placebo
Intervention Placebo
*P value = 0.016.
*P value = 0.01.

Mulyana R. The effect of Ophiocephalus striatus supplementation to IGF-1 and albumin serum in malnourished elderly patients. Thesis. Faculty of Medicine Universitas Indonesia. 2017.
 IGF-1
• Anabolic hormone; synthesized in the liver and local expressed in peripheral tissues under
the control of pituitary growth hormone (GH)
• During aging there is the gradual decline and alteration in GH secretion pattern and IGF-1
production  “Somatopause”  reduction of bone and muscle mass and strength
• Cappola et al. showed a significant correlation between IGF-1 levels and muscle
strength, only below IGF-1 threshold limit of 50 µg/L.
• Data from the Health, Aging and Body Composition Study showed a cross-sectional
relationship between low circulating IGF-1 levels and poor thigh muscle area and
density in a cohort of elderly subjects of both sexes.

Maggio M, et al. IGF-1, the Cross Road of the Nutritional, Inflammatory and Hormonal Pathways to Frailty. Nutrients. 2013;5:4184-4205.
 IGF-1 and Nutritional Status

When an energy and/or protein deprivation occurs, there is a significant reduction in plasma levels of IGF-
1.1

IGF-1 is also a potential and useful marker of malnutrition status, by defect or by excess, is supported by
the U-shape relationship existing between IGF-1 serum concentrations and body mass index.2

In a study of malnourished patients with renal failure, IGF-1 was found to be a more sensitive indicator of
malnutrition than classical nutritional markers such as albumin, pre-albumin, transferrin, and retinol-
binding protein.3

1. Norat T., Dossus L., Rinaldi S., Overvad K., Grønbaek H., Tjønneland A., Olsen A., Clavel-Chapelon F., Boutron-Ruault M.C., Boeing H., et al. Diet, serum insulin-like growth factor-I and IGF-binding protein-3 in European women. Eur. J. Clin.
Nutr. 2007;61:91–98.
2. Gran I.T., Norat T., Rinaldi S., Dossus L., Ulanova A., Téhard B., Clavel-Chapelon F., van Gils C.H., van Noord P.A., Peeters P.H., et al. Body mass index, waist circumference and waist-hip ratio and serum levels of IGF-I and IGFBP-3 in European women. Int. J.
Obes. 2006;30:1623–1631
3. Vehe K.L., Brown R.O., Moore L.W., Acchiardo S.R., Luther R.W. The efficacy of nutrition support in infected patients with chronic renal failure. Pharmacotherapy. 1991;11:303–307.
IGF-1 and Muscle Regulation
• Insulin-like growth factor-1 (IGF-1)
stimulates muscle growth via
phosphatidylinositol 3-kinase–Akt
signalling (PI3K/Akt).
• Active Akt has many significant
downstream actions:
• Modulates the phosphorylation of
mTOR, involved in cell proliferation
and growth, including protein
synthesis
• Skeletal muscle hypertrophy and has
also been shown to preserve muscle
fibres size in skeletal muscles
undergoing atrophy

Reilly B. Prevention of muscle wasting and osteoporosis: The value of examining novel animal models. Journal of Experimental Biology. 2016.
Conclusion
• Albumin can be one of the important protein marker because it can be used as both
nutritional and total protein marker.
• Several etiologies of hypoalbuminemia include malnutrition, chronic or critically ill
patients, sepsis, cirrhosis, renal and heart failure.
• Based on the current study, there is a promising effect of oral C. striata supplementation
as an alternative to albumin infusion in terms of increasing albumin level (when the
albumin level is above 2.5 g/dL) and IGF-1
• However, albumin infusion still needed in patients with several conditions based on the
guideline of albumin infusion in hypoalbuminemia
• Increase albumin and IGF-1 are important in increasing protein synthesis to prevent
sarcopenia, however further research is still needed to conclude this hypothesis.
Thank You
Indications Notes GoR
Contraindications to the use of non- - Pregnancy and breastfeeding 2C
protein colloids - Perinatal period and early infancy
- Acute liver failure
- Moderate-severe renal failure (particularly anuria/oligouria)
- Dialysis treatment in the presence of severe abnormalities of
haemostasis and baseline albumin <2-2.5 g/dL
- Intracranial haemorrhage
- Hypersensitivity
Haemorrhagic Shock Only in the case of: 1A
- Lack of response to crystalloids or colloids
- Contraindication to the use of non-protein colloids
Hepatorenal Syndrome In association with vasoconstricting drugs 2B
Nephrotic Syndrome Only in patients with albumin <2g/dL with hypovolemia and/or 2C
pulmonary edema
Organ Transplantation In the post-operative period after liver transplantation to control 1C
ascites and peripheral edema, to replace the loss of ascitic fluid
from the drainage tubes, if albumin <2.5 g/dL with a hematocrit
>30%
Liumbruno G, et al. Recommendations for the use of albumin and immunoglobulins. Blood Transfus. 2009;7(3):216-34.
AUTHORS Pattiha Paliliewu Retnaningsih, Restiana, et. al. Erwin, et. al. Mulyana R
(Year) 2011 2013 2014 2017
Evaluate the effects Evaluate the Evaluate the effects of Asess the effect of Asess the effect of Evaluate the effect
of Channa sp extract supplementation of snakehead fish extract Channa sp extract in Channa sp extract in of Ophiocephalus
in protein level snakehead extract in in protein status, protein status, albumin level triatus to IGF-1 and
AIM patients with inflammation responses. antioxidant and clinical outcome in patients with hepatic albumin serum in
HIV/AIDS. oxidative stress, and patients with cirrhosis and malnourished
clinical outcome in HIV/AIDS nephrotic syndrome. elderly patients
acute ischemic stroke
METHODS RCT (n= 36) RCT (n=36) RCT (n=61) RCT (n=25) RCT (n=20) RCT (n=90)
STUDIES 21 days 12 weeks 1 week 5 weeks 7 days 14 days
DURATION
•Higher pre albumin •The rate of positive •Significant increase in •Significant increase There is no There is significant
levels in intervention sputum smear decline albumin, transthyretin in body mass significant difference improvement in
group than placebo did not reach statistical (TTR), transferrin index, upper arm in albumin level albumin and IGF-1
(20.8 vs. 9 g/dL). significant difference (TFR), total antioxidant circumference, between two groups. between placebo
• Higher albumin between groups. status (SAT) and albumin, and Ophiocephalus
levels in intervention • At week 12, TNF-α, decrease in limphocyte, sp group.
RESULT group than placebo IFN-γ, IL-10 decreased malondialdehyd (MDA) energy intake.
in 4th, 7th, 14th, and significantly in and National Institute
21st day. intervention group of Health Stroke Scale
• No significant compared to baseline. (NIHSS).
difference CD4 levels
between groups in
21st day.
 Albumin as Nutritional Marker

• There is still a debate regarding the used of

albumin as nutritional marker in geriatric
patients without acute condition
• Study showed that albumin <3.5 g/dL as an
independent marker for malnutrition.

1. Kuzuya M, Izawa S, Enoki H, et al. Is serum albumin a good marker for malnutrition in the physically impaired elderly? Clin Nutr 2007;26:84–90.
2. Bharadwaj S, et al. Malnutrition: laboratory markers vs nutritional assessment. Gastroenterol Rep (Oxf). 2016;4(4):272-80