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Kolesterol – venn eller fiende?

Einar Sletten, professor emeritus, Kjemisk institutt, UiB

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Kolesterol

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Kolesterolnivå – målemetodeHDL: High-Density-Lipoprotein; LDL: Low-Density-Lipoprotein

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i) Total kolesterol: kolesteryl ester + H2O hydrosylase + kolesterol + fettsyre

ii) HDL – kolesterol (Sentrifugere ut HDL)

iii) Triglyserid (TG) triglyserid + lipase glyserol + fettsyre

iv) LDL - kolesterol = [total kol] - [HDL-kol] - [TG]/5

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Lever

80 %

HDL: High Density Lipoprotein transport frå celle til lever

LDL: Low Density Lipoprotein transport frå lever til celle

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Lipoprotein: HDL og LDL

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NMR-spektra

Lipoprotein

Proton Nuclear Magnetic Resonance Spectroscopy of Serum

Lipoproteins in Rabbits with Implanted VX-2 Carcinoma.

Gro Gadeholt, Svetlana Kruse, Line Halsteinslid and Einar Sletten

Eur. J. Cancer, Vol. 26, No. 5, pp. 61141S. 1990.

Kolesterol – hjerte-kar-sjukdom (HKS)

• 1840 Karl von Rokitansky «plaques» i blodårer

• 1904 Felix Marchand artherosclerosis

• 1913 Nikolai Anitschkov kaninforsøk, kolesterol

• 1953 Ancel Keys advarsel mot fett

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Fettsyrer

α

ωOmega-3 fettsyre

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Triglyserid (fett)

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Ancel Keys - mannen som lurte oss trill rundt

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Samanheng mellom fettrik diett og hjerte-kar sjukdom?

1958-1964

7 land

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”Saturated fats in the diet clogged arteries

and caused heart disease”

1961

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Drastisk skifte i folks diettvaner basert på Ancel Keys

Komplett datasett (22 land)

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«Scientists were wrong about saturated fats.

They don’t cause heart disease after all»

2014

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Eating fat is good for you:

Doctors change their minds after 40 years

The obsession with a low-fat diet has “paradoxically

increased” the risk of heart disease.

Cardiologist Dr Aseem Malhotra

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Ny studie, reviderte data, (1968 -1973),

9 000 pasientar på eldresenter i Minnesota.

1. Diett med umetta fett: 13 % lægre kolesterol nivå enn diett

med metta fett

2. “Surprising, the low cholesterol was actually associated

with an increased risk of dying”

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221972

Kolesterol – eit svært viktig molekyl !

• Cellemembranar 50% kolesterol

• Hjernen 25 % kolesterol

• Hormonar: cortisol, aldosteron, progesteron, estrogen, testosteron

• Vitaminar : syntese av A og D

• Co-enzym Q10

• Isolerer nervetrådar.

• Lågt kolesterolnivå kan gi helseproblem

• Eldre med høgt kolesterolnivå har best hukommelse!

Am. J. Geriatr Psychiatry Geriatr, 2008 Sep;16(9):78.

.

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Avleiring i kransarterier «plaque»

LDL

26Landé K, Sperry, W.: Arch Pathol 1936, 22:301-312.

Aorta-

fettinnhald

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• Hypotese: Kolesterol årsak til «plaque» i kransarterier

• Legemiddelindustrien foreslår: kolesterolnivå < 2-3 mmol

• Gjennomsnitt Norge: 5,6 mmol

• Statinar: Kolesterol-reduserande legemiddel

• Tilråding (USA): Start behandling i 8-årsalderen!

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National Cholesterol Education Program (NCEP).

Rettningslinjer for bruk av statinar.

«All members of the 2004 guideline participants had received

payments and/or grant funds from the following organisations»:

Abbott

Astra Zeneca

Bayer

Bristol-Myers Squibb

Glaxo

Merck

Pfizer

Novartis

Procter & Gamble

SmithKline

Statinar: Reduserer produksjon av kolesterol

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Syntese – 25 steg!

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Absolutt og relativ risiko

Eksempel: risiko for treff av lyn

Utendørs: 0.000002 %

Innandørs: 0.000001%

Absolutt Risiko Reduksjon: 0.000001%

Relativ Risiko Reduksjon: 50 %

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Behandling med Lipitor (statin)

Antal fatal non-fatal totalt

Lipitor 5168 40 60 100 ---> 1.9 %

Placebo 5237 46 108 154 ---> 3.0 %

Absolutt Risiko Reduksjon:............. 3.0 – 1.9 = 1.1 %

Relativ Risiko Reduksjon:.......(1.1/3.0) x 100 = 36.6 %

Statinbehandlig: «to save lives» ?

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Bi-effektar ved statinbehandling

Food and Drug Administration (FDA)

Drug Safety Communication: Important safety label changes

to cholesterol-lowering statin drugs (2012)

1. Muscle pain and damage

2. Liver damage

3. Neurological side effects

4. Polyneuropati

5 Increased blood sugar or type 2 diabetes

Increased risk of diabetes with statin treatment is

associated with impaired insulin sensitivity and insulin

secretion. M, Laakso et. al. Journal Diabetologia (2015)

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Loss of Life Expectancy Due to Various Causes

Causes Dagar

Being unmarried-male 3500

Cigarette smoking-male 2250

Heart disease 2100

Being unmarried-female 1600

Being 30% overweight 1300

Cancer 980

20% overweight 900

Motor vehicle accidents 207

Pneumonia-influenza 141

Alcohol (U.S. average) 130

Diabetes 95

Being murdered (homicide) 90

Drinking coffee 6

Bicycling 5

Nuclear accident 0,002

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Statin i Norge

start punkt

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(mg)

220 mg = 5.7 mmol

MONICA: 10 millionar personar, 21 land, 10 års periode

Per 100 000

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Kolesterol

mmol

Heart disease rates in men aged 35-74

MONICA project

Frankrike

Spania

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“The largest ever cardiology study has failed to

find a link between heart attacks and high

cholesterol levels.”

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i) EU: “New regulations on clinical trials in 2004”

iii) “After 2004 all clinical trials, performed by scientists free of

conflict of interest reported that statins were effective in

lowering LDL-C but no significant beneficial effects were

observed for the prevention of CHD”

USA Dietary Guidelines

Advisory Committee (2015)

“there is no scientific evidence

of a connection between

cholesterol intake and heart

disease”.

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Primary

prevention

Secondary

prevention

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i) Statinar Nr. 1 legemiddel på bestseljar lista

ii) Pfitzer (Lipitor) (1997-2011): $125 milliardar

iii) AstraZeneca’s Crestor: $5.2 milliardar dollar i 2013

iv) Lobbying (2005): $800 millionar til valgkampbidrag

v) Behandling: 19.2 % , (45-64); 39.6 %, (65-74); 44.3 % >75 år

vi) Anbefaling: 97 % alle menn (66 – 75 år) bør ta statinar!

vi) Statin bruk: Norge 1 av 5

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Kan vi lite på informasjon

frå Wikipedia?

«Pharmageddon»

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Nye medikament

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Evacetrapib: Tranformere LDL HDL

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12 000 CAD pasientar over tre år (avslutta oktober 2015)

• HDL auka med 130 %

• LDL avtok med 37%

• Konklusjon: "Here we have a paradox. The drug more than doubled

HDL and lowered LDL, but had no effect on cardiac events.” Steve

Nissen, chairman of Cardiovascular Medicine at Cleveland Clinic

Årsaker til hjarte-kar-sjukdom ?

• Skade på arteriene pga. inflammasjon

• Homocysteine nivå ?

• STRESS

• «Not everything that can be measured, matters, and

not everything that matters can be measured»

Albert Einstein

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"The great tragedy of science -- the slaying of a

beautiful hypothesis by an ugly fact."

-- Thomas Huxley

1825-1895

Takk for meg !

The Great Cholesterol Con:

The Truth About What Really Causes Heart Disease and How

to Avoid It.

Malcolm Kendrick (2008)

• www.thincs.org

• sletten.einar@gmail.com

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All forsking er ikkje god forsking

Ein gjennomgang av den mest siterte medisinske forskinga,

viste at mellom ein tredel og halvparten av konklusjonane

seinare blei motbevist.

Folk må lære seg å være kritisk til påstander om at noko er

vitskapeleg bevist, enten det gjeld helsestoff eller

klimaendringar

,

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“Historically, the claim of consensus has been the first

refuge of scoundrels; it is a way to avoid debate by

claiming that the matter is already settled. Whenever

you hear the consensus of scientists agrees on

something or other, reach for your wallet, because

you’re being had.” – Michael Crichton

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N Engl J Med. 2006 Apr 13;354(15):1578-88. Epub 2006 Mar 12.

Homocysteine lowering and cardiovascular events after acute

myocardial infarction.

Bønaa KH1, Njølstad I, Ueland PM, Schirmer H, Tverdal A, Steigen T,

Wang H, Nordrehaug JE, Arnesen E, Rasmussen K; NORVIT Trial

Investigators.

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