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NUTRISI UNTUK MENINGKATKAN DAYA

TAHAN TUBUH DALAM AKTIFITAS SEHARI


HARI
MENGHADAPI COVID 19

Nurpudji A Taslim
Perhimpunan Dokter Spesialis Gizi Klinik Indonesia
Dept. Ilmu Gizi Fakultas Kedokteran Universitas Hasanuddin
@2020
The Role of Vitamins
to improve immunity
Vitamins that Support The Immune System

Vitamin A

Vitamin
Vitamin C D
Immune
System
Vitamin E
Vitamin B6, B12,
Asam folat 3
The sites of action of vitamins on the
immune system

Epithelial Cellular Antibody


barriers immunity production
Vitamin A, Vitamin A, Vitamin A,
B6, B9, B6, B9, B6, B9,
B12, C, D, B12, C, D, B12, C, D,
E E E
Maggini, S et al, 2007. Selected vitamins and trace elements support immune function by strengthening epithelial barriers and cellular and
humoral immune responses. British Journal of Nutrition; Gombart AF, et al. 2020. A Review of Micronutrients and the Immune System–
Working in Harmony to Reduce the Risk of Infection. Nutrients 4
Roles of vitamins at every stage of the
immune response
g en Vitamin A,
ho
Pat Physical barrier (skin, GI Track, Respiratory track) B6, B9, B12,
1 C, D, E,

B9  survival of B6  lymphocyte Adifferentiation of


regulatory T cells in migration into the intestine epithelial tissue
the small intestine
C  collagen synthesis D  increases tight
B12 gut microbes and protects cell junction protein
metabolic membranes from ROS expression, E-cadherin
the gut
E  protects cell
membranes from ROS
Gombart AF, et al. 2020. A Review of Micronutrients and the Immune System–Working in Harmony to Reduce the Risk of Infection. Nutrients 5
Roles of vitamins at every stage of the
immune response
2 Innate Immune Response

Innate Immune cell proliferation,


Oxidative burst and self
differentiation, function and Antimicrobial activitiy
movement protection

Vitamin A, B6, Vitamin A, C, D


Vitamin C, E
B9, B12, C, D, E,
A, Eregulates number and function of
NK cells, phagocytic Protects against ROS A, C Downregulates IFN
B6, B9, B12NK cell cytotoxic activity and RNS during production
Cneutrophils, monocytes, phagocytes D  cathelicidin and defensin
Dphagocytic
oxidative burst
Gombart AF, et al. 2020. A Review of Micronutrients and the Immune System–Working in Harmony to Reduce the Risk of Infection. Nutrients 6
Roles of vitamins at every stage of the
immune response- Cont’
3
Regulation of
Inflamatory response inflammationVitamin A,
C, E, B6

AProduction of IL-2 and the B6synthesis and


proinflammatory TNF-α activates metabolism of amino
the microbial action of acids, the building blocks
macrophages of cytokines

Cmodulates cytokine
production, decreases EEnhances IL-2 production
histamine levels

7
Gombart AF, et al. 2020. A Review of Micronutrients and the Immune System–Working in Harmony to Reduce the Risk of Infection. Nutrients
Roles of vitamins at every stage of
the immune response- Cont’
4
T cell proliferation,
Adaptive Immune Antigen
differentiation and
function Vitamin
Response presentation A,D, C, E, B6, B12

Inhibitory actions
Humoral Vitamin D, E, B6
Cell mediated immunity
immunity

Vitamin A, D, C, E,
B6,B12, B9

Gombart AF, et al. 2020. A Review of Micronutrients and the Immune System–Working in Harmony to Reduce the Risk of Infection. Nutrients 8
Sumber Vitamin B6 ( AKG dewasa: 1,3-1,7
mg )

Per 100 gram:
 Ikan tuna – 0,933 mg
 Hati ayam – 0,755 mg
 Salmon – 0,611 mg
 Dada ayam tanpa kulit
– 0,513 mg
 Pisang – 0,367 mg
 Kentang – 0,269 mg
 Daging sapi – 0,268 mg
 Nasi dari beras coklat –
0,122 mg
Sumber Vitamin B12 (AKG dewasa: 4 mcg)

• Sumber dari makanan hewani


• Per 100 gram makanan:
- Nori – 76 mcg
- Kerang – 20,22 mcg
- Hati ayam – 16,71 mcg
- Ikan makarel/kembung – 7,56 mcg
- Salmon – 4,44 mcg
- Daging sapi – 2,6 mcg
- Tuna – 2,55 mcg
- Kuning telur – 1,87 mcg
- Susu sapi – 0,45 mcg
- Tempe – 0,14 mcg
Sumber Folat (AKG dewasa: 400 mcg)

• Per 100 gram makanan:


- Hati ayam – 573 mcg
- Bayam – 145 mcg
- Kacang tanah – 120
mcg
- Brokoli – 107 mcg
- Jeruk – 30 mcg
- Tahu – 27 mcg
- Stroberi – 24 mcg
- Tempe – 21 mcg
Vitamin D and Covid-19
■ Vitamin D and immune system:
– Vitamin D Receptors (VDR) found in T, B lymphocytes, Dendritic cells (DCs), monocytes,
macrophages, respiratory epithelial cells immunomodulatory, anti-inflammatory
– Vitamin D is anti-infection activities:
■ Physical barrier function: maintain tight junction, gap junctions, adheren junctions (E-
cadherin)
■ Enhance cellular immunity: inducing antimicrobial peptides: cathelicidine, LL37
■ Optimal serum levels: 40-60 ng/ml (100-150 nmol/L), deficiency <25-30 nmol/L

Grant, W. B. et al. (2020) ‘Evidence that vitamin d supplementation could reduce risk of influenza and
covid-19 infections and deaths’, Nutrients. MDPI AG. doi: 10.3390/nu12040988.
Vitamin D Studies in Covid-19 patients

■ No RCT in Covid-19 patients


■ Observational study in Switzerland :
retrospective design
– Covid-19 patients had lower
serum vitamin D

D’avolio, A. et al. (2020) ‘25-hydroxyvitamin D concentrations are lower in patients with


positive PCR for SARS-CoV-2’, Nutrients. MDPI AG, 12(5). doi: 10.3390/nu12051359.
Vitamin D Studies in Covid-19 patients

■ No RCT in Covid-19 patients


■ Observational study:
– The lower the serum Vit. D the
more the risk of contracting
Covid-19

Meltzer, D. O. et al. (2020) ‘Association of Vitamin D Deficiency and Treatment with COVID-19 Incidence’,
medrxiv. Cold Spring Harbor Laboratory Press, 1737(1), pp. 1–22. doi: 10.1101/2020.05.08.20095893.
Of
Interest
Vitamin D Studies in Non-Covid-19 Respiratory Infection

■ Double blind RCT high dose (250.000-500.000 IU)in ventilated critically ill
patients found to be safe decreased length of stay (LOS), improved oxygenation
(increased Hb)
■ Risk of acute viral respiratory infection 2 folds less and percentage of sick days 5
folds less if serum Vit. D > 95nmol/L

Ebadi, M. and Montano-Loza, A. J. (2020) ‘Perspective: improving vitamin D status in the management of COVID-
European Journal of Clinical Nutrition. Springer US. doi: 10.1038/s41430-020-0661-0.
Vitamin D Studies in Non-Covid-19 Respiratory
Infection prevention

Of
Interest
• Meta-analysis: 25 trials, 11321
participants from 14 countries, 4
continents
• Vit. D supplementation is protective
against acute respiratory tract
infection especially for those with
serum Vit. D < 25 nmol/L
• Daily or weekly doses is better than
combined with bolus doses
• No serious effect of Vit. D
supplementation

Martineau, A. R. et al. (2017) ‘Vitamin D supplementation to prevent acute respiratory tract infections: Systematic review and meta-analysis of
individual participant data’, BMJ (Online). BMJ Publishing Group, 356. doi: 10.1136/bmj.i6583.
Vitamin D Recommendations:
■ Vitamin D supplementation will benefit most those with low serum Vitamin D
■ Recommended supplementation 400-4000 IU( 10-100 ug)/day
■ Although Vit. D is safe even in higher doses, should be avoided
■ Daily 1000 IU/day for majority of people will maintain 25(OH)D >50 nmol/L

Lanham-New, S. A. et al. (2020) ‘Vitamin D and SARS-CoV-2 virus/COVID-19 disease’, BMJ


Nutrition, Prevention & Health, p. bmjnph-2020-000089. doi: 10.1136/bmjnph-2020-000089.

Zittermann, A. et al. (2016) ‘Vitamin D and airway infections: A European perspective’,


European Journal of Medical Research. BioMed Central Ltd. doi: 10.1186/s40001-016-0208-y.
Sumber Vitamin D (AKG dewasa: 15-20 mcg)

- Per 100 gram makanan


- Ikan makarel/kembung – 16,8 mcg
- Salmon – 13,7 mcg
- Kuning telur – 6,1 mcg
- Ikan sarden – 4,8 mcg
- Susu sapi – 1,3 mcg Catatan: kadar vit D berlebihan
- Tuna – 1,2 mcg dapat menurunkan daya tahan
tubuh

Berjemur pada pukul 09 selama 25 menit, atau antara pukul 11-


13 selama 7,5 menit  67,5 mcg per kali*
Pengaruh pajanan sinar ultraviolet B bersumber dari sinar matahari terhadap
konsentrasi vitamin D (25(OH)D) dan hormon paratiroid pada perempuan usia
lanjut Indonesia.
Vitamin C and Covid-19

■ Vitamin C is a strong antioxidant


■ There are evidence that level of Vit. C decreases in infection, sepsis,
ARDS
■ Some clinicians use IV Vit. C for Covid-19 patients, although there is
no current RCT or other evidence to support that
Vitamin C Study in non Covid-19 Of
Interest

■ An RCT, double blind, placebo


controlled, 7 ICU Unit, USA
■ N: 167
■ Dose: 50 mg/kg BW in dextrose 5%
every 6 hour for 96 hours (16
times)

JAMA. 2019;322(13):1261-1270.
doi:10.1001/jama.2019.11825
This multicenter, randomized, double-blinded trial
included 167 patients with sepsis and
ARDS who were randomized to receive 50 mg/kg
every 6 h of HDIVC for 4 days versus placebo and
showed statistically significant difference in 28-day
all-cause mortality 21
18 relevant
controlled trials
with a total of
2004 patients

In
In six
Inthreetrials,
12 trials orally
trials with
in administered
1766
which patients,
patients vitamin
vitamin
needed CCreduced
mechanicalinventilation
dosesthe offor
1–3
length
over
g/day
24 ICU(weighted
of hours,stay on C
vitamin mean
average 2.0 g/day)
bythe
shortened 7.8% reduced
(95%
duration ofCI:the
4.2%length
mechanical of ICUpby=
toventilation
11.2%;
18.2%
stay by(95%
0.00003) 8.6% CI (p
7.7% to 27%; p = 0.001)
= 0.003)
22
Large dose of IV Vit-C has shown successful clinical results in viral ARDS and influenza.
A young patient was recommended to take a high dose of IV Vit-C (50,000 mg of Vit-C in 1000
ml Ringer's solution, infused over 90 min) and the condition of the patient improved notably by
the next day. He was continued to take oral VC (2000 mg twice daily)
23
Sumber Vitamin C (AKG dewasa: 75-90 mg)

• Per 100 gram makanan:


- Kiwi – 92,7 mg
- Jambu biji - 87 mg
- Cabai hijau – 84 mg
- Pepaya – 78 mg
- Brokoli – 64,5 mg
- Stroberi – 58,8 mg
- Lemon – 50 mg
- Jeruk manis – 49 mg
Peran Vitamin A pada Covid-19
■ Perkembangan penelitian mengenai vitamin A terhadap beberapa virus, maka
suplementasi vitamin A berpotensi efektif diberikan sebagai pencegahan maupun
pengobatan penyakit infeksi virus termasuk covid-19.
■ Menurut penelitian Zhang, rekomendasi pemberian vitamin A adalah 5.000
IU/hari (1.500 µg RE) untuk pencegahan infeksi virus dan 20.000 IU/hari (6.000
µg RE) untuk terapi
■ Pasien Covid-19 dengan malnutrisi diberikan suplementasi vitamin A, vitamin D
dan mikronutrien lain seperti vitamin B, V, selenium, zink dan besi (ESPEN,
2020)
■ Defisiensi vitamin A pada hewan coba, menunjukan peningkatan risiko covid-19
(ASPEN, 2020)
■ Panduan Praktis Penatalaksanaan Nutrisi Covid-19 PDGKI direkomendasikan
pemberian vitamin A yaitu 650 µg RE/hari untuk laki-laki dan 600 µg RE/hari
untuk perempuan
Sumber Vitamin A (AKG dewasa: 600-650 mcg)


Per 100 gram
 Minyak ikan – 24.242
mcg
 Hati ayam – 4.957 mcg
 Mentega – 1.000 mcg
 Kuning telur – 606 mcg
 Cabai merah – 486 mcg
 Wortel – 333 mcg
 Bayam – 273,5 mcg
 Kangkung – 197,5 mcg
 Labu kuning – 131 mcg
Fungsi Zink
Zinc berperan dalam berbagai fungsi biologis, antara lain:
■ fungsi imunitas tubuh dan ekspresi informasi genetik,
■ pertahanan terhadap oksidan (sebagai antioksidan),
■ berperan dalam sintesis dan degradasi karbohidrat, lipid, protein, dan
asam nukleat,
■ komponen penting untuk stabilisasi struktur protein dan asam nukleat,
maupun integritas organel subselular,
■ sebagai katalisator dan penyusun struktur sel, dan juga berperan dalam
proses signaling sel,
■ mempertahankan struktur normal sitoskeleton.
Zink dan Covid-19
■ Beberapa penelitian membuktikan bahwa peningkatan kadar zink dapat menghambat
replikasi virus-virus RNA (Lanke et al., 2007; te Velthuis et al.,2010)
■ Empat pasien covid-19 diterapi zink dosis tinggi (Zinc salt oral lozenges, dosis total
sehari 115mg- 207 mg/hari) memperbaiki gejalanya (Finzi E, Case report, International
Journal of Infectious diseases 99,2020)
■ 5 kelompok penelitian mendukung hipotesis bahwa beratnya Covid-19 dapat diturunkan
dengan pemberian zink oral.( Moseley HNB, 2020)
■ Direkomendasikan untuk area berisiko tinggi/orang dengan suspek covid-19 sejak
awal diberikan suplementasi nutrisi adekuat ( zinc,selenium dan vitamin D).
(Alexander et al., Review, Nutrients, 2020).
■ Rekomendasi PDGKI: zink tablet 20 - 40 mg/hari.
Sumber Seng/Zink (AKG dewasa: 8-11 mg)

• Per 100 gram makanan:


- Tiram – 78,26 mg
- Kepiting – 3,79 mg
- Daging sapi – 5,2 mg
- Hati ayam – 3,95 mg
- Keju – 2,8-3,2 mg
- Kuning telur – 2,5 mg
A Review of Micronutrients and the Immune System–
Working in Harmony to Reduce the Risk of Infection
Adrian F. Gombart,  Adeline Pierre,  and  Silvia Maggini
1 2 2,*

Abstract
Immune support by micronutrients is historically based on vitamin C deficiency and supplementation in scurvy in
early times. It has since been established that the complex, integrated immune system needs multiple specific
micronutrients, including vitamins A, D, C, E, B6, and B12, folate, zinc, iron, copper, and selenium, which play vital,
often synergistic roles at every stage of the immune response. Adequate amounts are essential to ensure the proper
function of physical barriers and immune cells; however, daily micronutrient intakes necessary to support immune
function may be higher than current recommended dietary allowances. Certain populations have inadequate dietary
micronutrient intakes, and situations with increased requirements (e.g., infection, stress, and pollution) further
decrease stores within the body. Several micronutrients may be deficient, and even marginal deficiency may impair
immunity. Although contradictory data exist, available evidence indicates that supplementation with multiple
micronutrients with immune-supporting roles may modulate immune function and reduce the risk of infection.
Micronutrients with the strongest evidence for immune support are vitamins C and D and zinc. Better design of
human clinical studies addressing dosage and combinations of micronutrients in different populations are required to
substantiate the benefits of micronutrient supplementation against infection.
Keywords: immune system, infection, micronutrients, minerals, vitamins
Nutrients. 2020 Jan; 12(1): 236.  Published online 2020 Jan 16. doi: 10.3390/nu12010236
Sumber Vitamin E (AKG dewasa: 15-20 mg)
• Per 100 gram makanan:
- Minyak bunga matahari – 51
mg
- Kuaci bunga matahari – 26,1
mg
- Almond – 25,97 mg
- Minyak jagung – 21 mg
- Minyak kacang kedelai – 18 mg
- Minyak kanola – 17,46 mg
- Minyak kelapa sawit – 15,94 mg
- Margarin – 15 mg
- Minyak zaitun – 14,35 mg
- Minyak kacang tanah – 13 mg
Sumber Selenium (AKG dewasa: 24-30 mcg)

• Sangat tergantung kadar


di tanah
• Terdapat pada nasi,
jeroan, daging, dan susu
Sumber Tembaga (AKG dewasa: 0,9 mg)

• Per 100 gram makanan:


- Tiram – 4,4 mg
- Cokelat – 3,79 mg
- Lobster – 1,94 mg
- Kacang dan biji-bijian – 1,1-2,22
mg
- Hati ayam – 0,84 mg
Sumber Besi

(AKG dewasa: laki-laki 9 mg,


perempuan 8-18 mg)
• Per 100 gram makanan:
- Hati ayam – 15,8 mg
- Kerang – 15,6 mg
- Tiram – 8,26 mg
- Bayam – 5,7 mg
- Tempe – 4,9 mg
- Kangkung – 4,4 mg
- Tahu – 4,1 mg
- Daging sapi – 2,8 mg
Omega 3 Fish Oil pada Covid-19
■ Kandungan omega 3 EPA dan DHA memiliki efek menguntungkan pada
fungsi utama biologis, termasuk modulasi respon imun dan inflamasi.
■ Fish oil dapat menurunankan kejadian thrombosis.
■ Beberapa penelitian menunjukkan manfaat pemberian omega 3:
peningkatan perbaikan hasil klinis, mis. tingkat infeksi, tingkat sepsis,
penggunaan ventilator, lama rawat ICU dan di rumah sakit (Pradelli
L,2019).
■ Waktu kritis terjadinya hiperinflamasi/ mulai badai sitokin dihari 8-12
setelah onset gejala yang ditandai dengan pneumonia. Belum ada
rekomendasi khusus pemberian formula yang diperkaya omega 3 pada
pasien covid19.
■ Rekomendasi ESPEN : omega 3 ada tempatnya pada ARDS. Namun
pemberian pada ARDS dan Sepsis berat tidak diperbolehkan .
Sumber EPA dan DHA

• Per 100 gram makanan:


- Ikan makarel/kembung –
0,94 g dan 1,522 g
- Sarden – 0,473 g dan 0,509 g
- Salmon – 0,229 g dan 0,419
g
- Tiram – 0,352 g dan 0,271
g
• Minyak ikan (lihat label)
37
Linus Pauling Institute,2018. Nutrition And The Immune System
Rainbow on your plate

38
TERAPKAN KONSUMSI MAKANAN
YANG BERGIZI DAN SEIMBANG

• Susunan pangan sehari-hari yang mengandung zat gizi dalam


jenis dan jumlah yang sesuai dengan kebutuhan tubuh,
dengan memperhatikan prinsip keanekaragaman pangan,
aktivitas fisik, perilaku hidup bersih dan
mempertahankan berat badan normal untuk mencegah
masalah gizi (Kementerian Kesehatan RI, 2014)
Mencegah lebih mudah dari pada mengobati

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