Hypoalbuminemia The Role of Oral Albumin

Supplementation in Elderly

Siti Setiati

Albumin

• Albumin is the mostabundant protein plasma,with more than 50% ofplasma protein were made.

• Albumin is synthesizedin the liver, pre-albumin pro-albumin Golgiapparatus that will changepro-albumin albumin secreted by hepatocytes

1. Gounden J, Jialal I. Hypoalbumenia. 20152. 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 albumin is between 35 until 50 g/L

Hypoalbuminemia is when the 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)

2667

55

4611

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

Kadar Albumin

Jumlah Pasien di RSCM

1679

1387

<2,5 MG/DL >2,5 MG/DL

Kadar Albumin

Perubahan Kadar Albumin PascaTransfusi di RSCM

Etiology of Hypoalbuminemia

Gatta A, et al. Hypoalbuminemia. Intern Emerg Med. 2012;7(Suppl 3):S193-9.

Decrease Synthesis

Increase Catabolism

Distribution Alteration

Increase Clearance

• Cirrhosis• Malabsorption

syndrome• Nutrition

deficiency(decrease intake)

• Critically ill

• Infection• Sepsis• Cancer

• Hemodilution• Decrease

lymphaticclearance

• Increasetranscapillary:heart failure,vasculitis,diabetes

• Renal: Nephroticsyndrome

• Severe burnwound

• GI Tract:Enteropathy

239

116

116

105

84

83

79

66

62

52

49

48

0 50 100 150 200 250 300

A41.9 - SEPTICAEMIA, UNSPECIFIED

J18.9 - PNEUMONIA, UNSPECIFIED

P36.9 - BACTERIAL SEPSIS OF …

C53.9 - MALIGNANT NEOPLASM OF …

Q21.0 - VENTRICULAR SEPTAL DEFECT

E11.5 - DM WITH PERIPHERAL …

Q21.3 - TETRALOGY OF FALLOT

P07.3 - OTHER PRETERM INFANTS

C56 - MALIGNANT NEOPLASM OF …

Z51.1 - CHEMOTHERAPY SESSION FOR …

K74.6 - CIRRHOSIS OF LIVER

N04.9 - NEPHROTIC SYNDROME, …

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Jumlah Pasien di RSCM

Hypoalbuminemia Profile in RSCM (2017)

Hypoalbuminemia in Surgical or ICU

Patients

• Hypoalbuminemia is a predictor of increasedmortality and morbidity

• Meta-analyses of cohort studies and controlledtrials in acutely ill patients showed that eachdecrease of 10 g litre-1 in plasma albuminconcentration significantly raised the odds of:

• Mortality by 137%

• Morbidity by 89%

• Prolonged ICU by 28%

• Hospital stay by 71%

2017; retrospective cohort study

The mean length of hospitalization was significantlylonger with mild and marked hypoalbuminemia (7 ± 8and 9 ± 11 days, respectively) compared with patientswith 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 markedhypoalbuminemia was higher thanmild hypoalbuminemia

• The same result was also found inmortality at the end of follow-up(around 3-4 years)

• In addition, the mean ± SD serumalbumin levels were lower withincreased age (P < .001 for allcomparisons).

Hypoalbuminemia Management

• Finding out the main cause ofhypoalbuminemia and treat the maincause

• Albumin transfusion may be needed inseveral condition

Albumin Infusion IndicationINDICATIONS 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 more than one session

2C+

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 periodOnly indication for use: serum albumin <2 g/dL after normalisation of circulatory volume

2C+

Cirrhosis of the liver with refractory ascites

Generally ineffective, except in patients with serum albumin <2g/dL 2C

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 oedemaand/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 atdepths of 1-2 m, rarely below 10 meters.

• This species can be found in most types of slow-movingfreshwater habitat, including rivers, lakes, ponds, canals,creeks, flooded rice paddies, irrigation reservoirs, andswamps.

https://animaldiversity.org/accounts/Channa_striata/

Channa striata / Snakehead Fish / Ophiocephalusstriatus / Ikan Gabus

• Predacious, ambush feeding fish that has a carnivorous -specifically piscivorous - diet.

• Adult Channa hunt on their own, feeding on other adultfish, and the progeny of those fish. They can also feedon frogs, snakes, insects, earthworms, tadpoles, birds,small mammals, and crustaceans.

• Some cultures use snakehead muscle tissue and oils toheal wounds, prevent scarring, and administer it tothose recovering from surgery or sickness.

https://animaldiversity.org/accounts/Channa_striata/

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.

Nutritional Composition of C. striatusIntake of 2,5 grams of leucine stimulated Muscle protein synthesis (MPS)

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.

Thesis by Nugroho

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

•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.

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.

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

Perbandingan Kenaikan Serum Albumin Setelah Suplementasi KapsulEkstrak Ikan Gabus Dan Putih Telur Ayam Ras Pada Pasien Sepsis Di RS

H.Adam Malik

Thesis by Puteh

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

•Design Study: RCT

Purpose of this study is to get an alternative for increasing plasma albumin concentration inpatients 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)

Perbandingan Kenaikan Serum Albumin Setelah Suplementasi KapsulEkstrak Ikan Gabus Dan Putih Telur Ayam Ras Pada Pasien Sepsis Di RS

H.Adam Malik

• The mean Albumin in the Vipalbumingroup day-0 was 3,06 and on day-3 was3,19. P-value= 0,096.

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

• The mean albumin difference inVipalbumin group was 0,13 and on theegg white group was -0,13, p-value was0,04

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

0

0.5

1

1.5

2

2.5

3

3.5

Day-0 Day-3

Albumin Level

VipAlbumin Egg Whites

Thesis by Puteh

The effect of Ophiocephalus striatus supplementation to IGF-1 and albumin serum in malnourished elderly patients

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.

Roza Mulyana, Siti Setiati

•Design Study: RCT

•Total Subjects:

• 90 malnourished elderly patients: Intervention group (consumed snakehead fish extract 10gr/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 positivelyregulated 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 ofalbumin level.

The effect of Ophiocephalus striatus supplementation to IGF-1 and albumin serum in malnourished elderly patients

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.

47.8

60.4

44.2 45.9

0

20

40

60

80

Day-0 Day-14

IGF-1 (ng/dL) Level Comparison at Baseline and Day-14

Intervention Placebo

3.11

3.59

3.093.25

2.8

3

3.2

3.4

3.6

3.8

Day-0 Day-14

Albumin (g/dL) Level Comparison at Baseline and Day-14

Intervention Placebo

*P value = 0.01.*P value = 0.016.

IGF-1

• Anabolic hormone; synthesized in the liver and local expressed in peripheral tissues underthe control of pituitary growth hormone (GH)

• During aging there is the gradual decline and alteration in GH secretion pattern and IGF-1production “Somatopause” reduction of bone and muscle mass and strength

• Cappola et al. showed a significant correlation between IGF-1 levels and musclestrength, only below IGF-1 threshold limit of 50 µg/L.

• Data from the Health, Aging and Body Composition Study showed a cross-sectionalrelationship between low circulating IGF-1 levels and poor thigh muscle area anddensity 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 viaphosphatidylinositol 3-kinase–Aktsignalling (PI3K/Akt).

• Active Akt has many significantdownstream actions:• Modulates the phosphorylation of

mTOR, involved in cell proliferationand growth, including proteinsynthesis

• Skeletal muscle hypertrophy and hasalso been shown to preserve musclefibres size in skeletal musclesundergoing 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 bothnutritional and total protein marker.

• Several etiologies of hypoalbuminemia include malnutrition, chronic or critically illpatients, sepsis, cirrhosis, renal and heart failure.

• Based on the current study, there is a promising effect of oral C. striata supplementationas an alternative to albumin infusion in terms of increasing albumin level (when thealbumin level is above 2.5 g/dL) and IGF-1

• However, albumin infusion still needed in patients with several conditions based on theguideline of albumin infusion in hypoalbuminemia

• Increase albumin and IGF-1 are important in increasing protein synthesis to preventsarcopenia, however further research is still needed to conclude this hypothesis.

Thank You

Indications Notes GoR

Contraindications to the use of non-protein colloids

- Pregnancy and breastfeeding- 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

2C

Haemorrhagic Shock Only in the case of:- Lack of response to crystalloids or colloids- Contraindication to the use of non-protein colloids

1A

Hepatorenal Syndrome In association with vasoconstricting drugs 2B

Nephrotic Syndrome Only in patients with albumin <2g/dL with hypovolemia and/orpulmonary edema

2C

Organ Transplantation In the post-operative period after liver transplantation to controlascites and peripheral edema, to replace the loss of ascitic fluidfrom the drainage tubes, if albumin <2.5 g/dL with a hematocrit>30%

1C

Liumbruno G, et al. Recommendations for the use of albumin and immunoglobulins. Blood Transfus. 2009;7(3):216-34.

AUTHORS

(Year)

Pattiha2011

Paliliewu2013

Retnaningsih,

2014

Restiana, et. al. Erwin, et. al. Mulyana R

2017

AIM

Evaluate the effects of Channa sp extract in protein level patients with HIV/AIDS.

Evaluate the

supplementation of

snakehead extract in

inflammation responses.

Evaluate the effects of snakehead fish extract in protein status, antioxidant and oxidative stress, and clinical outcome in acute ischemic stroke

Asess the effect of Channa sp extract in protein status, clinical outcome in patients with HIV/AIDS

Asess the effect of Channa sp extract in albumin level patients with hepatic cirrhosis and nephrotic syndrome.

Evaluate the effect of Ophiocephalustriatus to IGF-1 and albumin serum in malnourished elderly patients

METHODS RCT (n= 36) RCT (n=36) RCT (n=61) RCT (n=25) RCT (n=20) RCT (n=90)

STUDIES

DURATION21 days 12 weeks 1 week 5 weeks 7 days 14 days

RESULT

•Higher pre albumin levels in intervention group than placebo (20.8 vs. 9 g/dL).• Higher albumin levels in intervention group than placebo in 4th, 7th, 14th, and 21st day.• No significant difference CD4 levels between groups in 21st day.

•The rate of positive sputum smear decline did not reach statistical significant difference between groups.• At week 12, TNF-α, IFN-γ, IL-10 decreased significantly in intervention group compared to baseline.

•Significant increase in albumin, transthyretin(TTR), transferrin (TFR), total antioxidant status (SAT) and decrease in malondialdehyd (MDA) and National Institute of Health Stroke Scale (NIHSS).

•Significant increase in body mass index, upper arm circumference, albumin, limphocyte, energy intake.

There is no significant difference in albumin level between two groups.

There is significant improvement in albumin and IGF-1 between placebo and Ophiocephalus sp group.

Albumin as Nutritional Marker

• There is still a debate regarding the used ofalbumin as nutritional marker in geriatricpatients without acute condition

• Study showed that albumin <3.5 g/dL as anindependent 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