Menyikapi Diet yang Populer di Masyarakat: Ketofastosis

Widjaja LukitoAfiliasi akademik:

PPDS-1, Program Studi Ilmu Gizi KlinikFakultas Kedokteran, Universitas Indonesia

Pertemuan Ilmiah Tahunan IDI Cabang Tangerang

Tangerang, 10 Pebruari 2018

(Very) low energy diet

Low GI diet

High fiber diet

Low fat diet (low SFA, high MUFA)

High protein diet

DASH diet

Well documented diets that lead to reduction in body weight, adiposity, body compositional, and glycemic control

Definisi: ketogenic diet dan ketofastosis (1)

Ketogenic diet is a high-fat, adequate-protein, low-carbohydrate diet that in medicine is used primarily to treat difficult-to-control (refractory) epilepsy in children (Wikipedia).

Substrat energi untuk neuron selama puasa

Grabacka M et al. Int J Mol Sci 2016;17:2093; doi:10.3390/ijms17122093

Definisi: ketogenic diet dan ketofastosis (2)

Dengan berpuasa, tubuh menghasilkan ketone bodies sebagai hasil lipolisis dan metabolisme asam lemak. Pendekatan ketogenic diet ‘memaksa’ akselerasi dan peningkatan metabolisme lemak dan asam lemak akibat (sangat) rendahnya asupan karbohidrat.

Dengan tujuan meningkatkan ‘efficacy’ ketogenic diet terhadap berbagai parameter metabolik, maka diperkenalkanlah pendekatan puasa (fasting)dalam keadaan ketogenic diet yang sering disebut ketofastosis

Metabolisme Lemak

Trigliserida

(Fat)

Asam lemak

Asetil Ko-A

Diet

Lip

olis

is

Este

rifi

kasi

Lip

og

en

esis

-o

ksid

asi

Kholesterol

Ketone

bodies

Ketogenesis

Digestion and transport of fats: LCT vs MCT

Metabolic efficiency of fats: LCT vs MCT

Typical vs ketogenic diets

Metabolic overview of ketogenic diets

Food choices for ketogenic diet (1)

Food choices for ketogenic diet (2)

Lima variant KD yang digunakan di seluruh dunia

CKD: classical ketogenic diet

MCTKD: MCT ketogenic diet

LGIT: low-glycemic index treatment

MAD: modified Atkins diet

MKD: modified ketogenic diet

Blood level Normal diet Ketogenic diet Diabetic ketoacidosis

Glucose (mg/dL) 80-120 65-80 > 300

Insulin (µU/L) 6-23 6.6-9.4 ≈ 0

KB (mM/L) 0.1 7/8 > 25

pH 7.4 7.4 < 7.3

Konsentrasi berbagai parameter metabolik saat diet normal, ketogenic diet dan diabetic ketoacidosis

Paoli A et al. Eur J Clin Nutr 2013;67:789-96

Nutritional appraisal of ketogenic diet and ketofastosis:

Hypothetical vs Real Life

Beberapa hal yang perlu diperhatikan pada ketogenic diet dan ketofastosis

Bahwa formulasi diet mengikuti kaidah-kaidah preskripsi nutrisi untuk tujuan-tujuan tertentu (dalam hal ini penurunan berat badan) dengan target asupan total kalori perhari (misalnya 15-20 Kkal/kg BB/hari).

Dengan memperhatikan poin pertama, maka sebenarnya asupan lemak yang dianjurkan bukanlah asupan ad libitum, namun tetap terbatas pada kerangka preskripsi nutrisi yang dianjurkan.

UK COMA US National Task Force

Energy content of VLED Min 1.7 MJ (400 kcal) per day for

women and 2.1 MJ (500 kcal) per

day for men

Less than 3.4 MJ (800 kcal) per day

Protein intake 40 – 50 g/day of high biological

value protein for men and women

0.8 – 1.5 g/kg of ideal body weight

Vitamins and minerals At least meet the UK reference

nutrient intake

Full complement of recommended

daily allowance

Clinical application 1. VLED should only be used under medical supervision

2. In obese individuals with BMI greater than 30, who are refractory to more

moderate dietary interventions

Restriction 1. VLED be used for periods of no

more than 4 weeks

2. Repeated use is not encouraged

-

COMA, Committee on Medical Aspects of Food Policy. Source: references 13 and 14, quoted in 12.

UK COMA and US National Task Force on the Prevention and Treatment of Obesity’s Recommendations on VLED

Energy restriction Nutrient partitioning Fuel partitioning

Medium-chaintriglyceride

Calcium anddairy

Functional foods:tea

Low energydensity

Lowglycemic index

Low carbohydrate

Balancedlow energy

Low energy

Verylow energy

Conjugated linoleic acid

Options for Nutritional Prescription in the Management of Obesity

Components of energy expenditure

BMR

Activity

Thermogenesis

Diet-induced thermogenesisThermoregulatoryAdaptive thermogenesis

Medium-chaintriglyceride

Calcium anddairy

Functional foods:tea

Conjugated linoleic acid

Lukito, 2005. Nutritional Pendulum in the Management of Obesity: Where is the Current Position? The 4th National Obesity Symposium. Makassar, 24-25 July 2005.

Implikasi nutrisi pada ketogenic diet dan ketofastosis

Extreme unbalanced low energy diet.

High diet-induced thermogenesis akibat pemberian MCT dan energy costyang meningkat akibat proses glukoneogenesis dari asam amino (high protein diet).

High and low fiber intake.

Kontrol nafsu makan yang lebih baik akibat tinggi protein dan ketone bodies.

Rendahnya respiratory quotient akibat sangat rendahnya karbohidrat sehingga meningkatkan efisiensi metabolisme lemak.

Diabetes Prevention Program:Weight Loss

Reprinted from Diabetes Prevention Program Research Group. N Engl J Med. 2002;346:393-403. Copyright © 2002 Massachusetts Medical Society. All rights reserved.

Change in W

eig

ht

(kg)

Year

Placebo

0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0

Metformin

Lifestyle

-8

-6

-4

-2

0

2

4Period of weight regain

Look AHEAD:Action for Health in Diabetes

• Clinical trial of 5,145 adults with type 2 diabetes

• Subjects were 45 to 74 years of age and were obese or overweight (body mass index >25 kg/m2 or >27 kg/m2 if taking insulin) at the time of enrollment

• Study Design: Group-based lifestyle modification program using meal replacements and optional pharmacotherapy (n = 2,570) versus usual care (n = 2,575)

• Study Question: Will intentional weight loss reduce the incidence of fatal and nonfatal cardiovascular and cerebrovascular events?

Look AHEAD Research Group. Control Clin Trials. 2003;24:610-628.

Lifestyle Modification

Low-Calorie

Diet

IncreasedPhysical

Activity

Behavior

Therapy

Percentage reduction in initial weight over 4 years for participants in the intensive lifestyle intervention and diabetes support and education groups of the Look AHEAD (Action for Health in Diabetes) study.

Wadden T et al. Circulation 2012;125:1157-1170

Period of weight regain

Percentage reduction in initial weight for overweight or obese women assigned to 1 of 4 exercise prescriptions (in addition to a 1200–1500 kcal/d diet): moderate-intensity/moderate-energy expenditure (expend 1000 kcal/wk), moderate-intensity/high-energy expenditure

Wadden T et al. Circulation 2012;125:1157-1170

Period of weight regain

Weight loss patterns

• Short-term effectiveness of dieting is frequently high, but ........

• Long-term maintenance seems more difficult.

Long-term success rate of body weight reduction < inital success.

Body weight regulation

Marti et al. Int J Obes. 2004;28:S29-36

Karyogram depicting loci that have been associated with body weight loss in

response to a nutritional intervention.

Leticia Goni et al. J. Nutr. 2016;146:905S-912S

Genes regulating metabolic functions that have been related to genetically-mediated differences to dietary treatments seeking weight loss.

V

V

V

V

Low energy diet in the management of body weight

• Total energy expenditure = resting metabolic rate (RMR) + physical activity energy

expenditure

• Some people have a lower RMR than others

• Dependent on a variant of the UCP1 gene

• Based on individual’s genotype for UCP1, recommend target energy deficit for

weight loss

Nagai et al. Int J Obesity. 2011;35:1050-1055.

Variation in resting metabolic rate (RMR) by UCP1 genotype

* Diminished RMR in those with the GG or GA variant compared to those with the AA variant.

Nagai et al. Int J Obesity. 2011;35:1050-1055.

High protein diet in the management of body weight

• Some people have an enhanced weight loss response with a moderate-to-high

protein diet

• Dependent on a variant of the FTO genotype

• Based on individual’s genotype for FTO, we can recommend target protein

intake

Zhang et al. Diabetes 2012;61:3005-3011.

Diabetes 2012;61:3005-3011.

• 811 overweight and obese (BMI ranged from 25 to 40 kg/m2), 61% were women.

• Randomly assigned to 4 diets with FPC compositions: 20, 15, and 65%; 20, 25, and 55%; 40, 15, and 45%; 40, 25 and 35%.

• After 2 years, 80% of total participants completed the trial.

Loss of fat mass (%) after 2 years with low or high protein calorie-controlled diet by FTO genotype

* Significantly greater weight loss in response to a moderate-to-high protein diet only in individuals with the AA genotype.

Zhang et al. Diabetes 2012;61:3005-3011.

Low fat diet in the management of body weight

• Some people have an enhanced weight loss response with low fat diet,

• Dependent on a variant of the TCF7L2 gene

• Based on individual’s genotype for TCF7L2, we can recommend targeted dietary

fat intake

Grau et al. Am J Clin Nutr. 2010;91:472-479.

Weight loss and change in waist circumference after low-fat diet by TCF7L2 genotype.

* Significantly greater weight loss in response to a low fat diet only in individuals with the TT genotype of TCF7L2.

Adapted from Grau et al. Am J Clin Nutr. 2010;91:472-479.

Implikasi klinis ketogenic diet dan ketofastosis

Awal menjalankan KD dan ketofastosis: bau napas dan mulut, muscle cramp, lemah tubuh, gangguan konsentrasi,

Gangguan keseimbangan elektrolit,

Beberapa kondisi klinis akibat meningkatnya metabolisme asam amino seperti:

1. gangguan fungsi ginjal

2. hipertensi pada sindroma metabolik dan pasien dengan transplantasi ginjal

3. hipotensi akibat proses glukoneogenesis

Harmful effects of high protein diet in CKD

Increase in protein degradation

Increase in degradation of branched chain amino acids

Over-accumulation of nitrogen and exacerbation of uremia

Water-sodium retention tends to evoke hypertension

Aggravation of secondary hyperparathyroidism

Exacerbates proteinuria and diminishes ACEi sensitivity

Woods LL. Kidney Int. 1993; 44:659.

King AJ. J. Am. Soc. Nephrol. 1993; 3:1723

Therapeutic action of ketogenic diets in various pathologic conditions

Paoli A et al. Eur J Clin Nutr 2013;67:789-96

Rangkuman

Preskripsi ketogenic diet dan ketofastosis untuk penurunan berat badan dan kontrol metabolik harus memperhatikan aspek long-term safety, long-term efficacy (efficacy terbaik pada mereka yang memiliki allele AA pada genUCP1 rs 1800592; allele AA pada gen FTO rs 1558902; dan allele TC dan CC pada gen TCF7L2 rs 7903146) dan quality of life.

Mengingat ketogenic diet dan ketofastosis termasuk kategori extreme low-energy unbalanced diet, sebaiknya di bawah pengawasan dokter.

Preskripsi ketogenic diet dan ketofastosis ketogenic diet dan ketofastosis sebaiknya tidak diberikan pasien-pasien dengan CKD, uncontrolled diabetes, diabetic nephropathy, risiko kanker (dietary fat-related cancers)dan lansia.

Balanced (low-energy) diet lebih sesuai untuk preskripsi nutrisi pada pasien-pasien dengan CKD, uncontrolled diabetes, diabetic nephropathy, risiko kanker (dietary fat-related cancers) dan lansia

Terima kasih