dr. peter j.e. verdegem chief scientific officer
TRANSCRIPT
![Page 1: Dr. Peter J.E. Verdegem Chief Scientific Officer](https://reader036.vdocuments.us/reader036/viewer/2022062320/56649cc45503460f9498d852/html5/thumbnails/1.jpg)
Dr. Peter J.E. VerdegemChief Scientific Officer
![Page 2: Dr. Peter J.E. Verdegem Chief Scientific Officer](https://reader036.vdocuments.us/reader036/viewer/2022062320/56649cc45503460f9498d852/html5/thumbnails/2.jpg)
Causes of Cardiovascular DiseaseCauses of Cardiovascular Disease
Atherosclerosis
Myocardial Ischemia
Arythmia, Angina, Heart Attacks
Heart Failure
Cholesterol Genetics SmokingAlcohol
![Page 3: Dr. Peter J.E. Verdegem Chief Scientific Officer](https://reader036.vdocuments.us/reader036/viewer/2022062320/56649cc45503460f9498d852/html5/thumbnails/3.jpg)
Cellular energy metabolismCellular energy metabolism
GlucoseFFA
Pyruvate
glycogenglucose 6P
glycolyse
ATP
Ca2+
Krebscycle
NADH2
FADH2
electron transport chain
O2
PCrADP
ATPCr
ADP
ATP
CKmyo
ATP ase
ATP
CKmito
ATP ase
ATP ase
ATP ase
actin/myosin
filaments
sarcoplasmicreticulum
mitochondrion
Calcium pumpand
Calcium channel
CKmyo
ADP
Ca2+
Lactate
Heart function
![Page 4: Dr. Peter J.E. Verdegem Chief Scientific Officer](https://reader036.vdocuments.us/reader036/viewer/2022062320/56649cc45503460f9498d852/html5/thumbnails/4.jpg)
Energy metabolism and Heart Function
Cellular abnormalities
Energy metabolism and Heart Function
Cellular abnormalities
• Gradual accumulation of calcium in myocytes
• Mitochondrial calcium overload
• Decreased myocyte energy production
• Increased oxidative damage and protease activation
• Myocyte dysfunction and death
• Gradual accumulation of calcium in myocytes
• Mitochondrial calcium overload
• Decreased myocyte energy production
• Increased oxidative damage and protease activation
• Myocyte dysfunction and death
Sole 2000, Curr Opin Clin Nutr Metab CareSole 2000, Curr Opin Clin Nutr Metab Care
![Page 5: Dr. Peter J.E. Verdegem Chief Scientific Officer](https://reader036.vdocuments.us/reader036/viewer/2022062320/56649cc45503460f9498d852/html5/thumbnails/5.jpg)
HomocysteineRole of folic acidHomocysteine
Role of folic acid
• Folic acid supplementation (0.2 - 1.0 mg/d) reduces plasma homocysteine levels up to 50 % (various studies)
• Folic acid enriched cereals in US• Folic acid supplementation (0.4 mg/d) might prevent 8%
of CVD deaths in US (estimation from meta-analysis)
• Folic acid supplementation (0.2 - 1.0 mg/d) reduces plasma homocysteine levels up to 50 % (various studies)
• Folic acid enriched cereals in US• Folic acid supplementation (0.4 mg/d) might prevent 8%
of CVD deaths in US (estimation from meta-analysis)
Brouwer 1998: AJCN, Ward 1997: Q J M.
Boushy 1995: J Am Med Ass.
![Page 6: Dr. Peter J.E. Verdegem Chief Scientific Officer](https://reader036.vdocuments.us/reader036/viewer/2022062320/56649cc45503460f9498d852/html5/thumbnails/6.jpg)
CVD and elevated homocysteine
CVD and elevated homocysteine
NIR
SCO1SCO2 FIN
GER1
FAO
GER2
DENICEISR
SPAFRAJAP
0
100
200
300
400
500
600
700
6 7 8 9 10 11 12
Plasma total homocysteine (umol/L)
CV
D m
orta
lity
per
100
,000
Alfthan 1997
An increase in plasma tHcy of 1 micromol/L increases CVD risk with 10 %
![Page 7: Dr. Peter J.E. Verdegem Chief Scientific Officer](https://reader036.vdocuments.us/reader036/viewer/2022062320/56649cc45503460f9498d852/html5/thumbnails/7.jpg)
Homocysteine metabolismHomocysteine metabolism
Methionine
Homocysteine
Vit.B12
THF
Cystathionine
Cysteine
Vit.B6
Vit.B6
Methylene-THF
MethylTHF
Folate
Zn
![Page 8: Dr. Peter J.E. Verdegem Chief Scientific Officer](https://reader036.vdocuments.us/reader036/viewer/2022062320/56649cc45503460f9498d852/html5/thumbnails/8.jpg)
Coenzyme Q10Coenzyme Q10
• Small fat soluble molecule with distinct functions:
• Transport of electrons to mitochondria, essential for energy production
• Fat soluble antioxidant protecting a.o. LDL particles
• A high concentration of Co Q10 is found in the heart muscle
• Small fat soluble molecule with distinct functions:
• Transport of electrons to mitochondria, essential for energy production
• Fat soluble antioxidant protecting a.o. LDL particles
• A high concentration of Co Q10 is found in the heart muscle
![Page 9: Dr. Peter J.E. Verdegem Chief Scientific Officer](https://reader036.vdocuments.us/reader036/viewer/2022062320/56649cc45503460f9498d852/html5/thumbnails/9.jpg)
Coenzyme Q10Coenzyme Q10
• Functions in energy production within the mitochondria
• Deficiency states have been demonstrated in the research
to be associated with many diseases, primarily
cardiovascular
(Bliznakow EG, et al. Adv in Ther. 1998;15(4):218‑228)
• Functions in energy production within the mitochondria
• Deficiency states have been demonstrated in the research
to be associated with many diseases, primarily
cardiovascular
(Bliznakow EG, et al. Adv in Ther. 1998;15(4):218‑228)
![Page 10: Dr. Peter J.E. Verdegem Chief Scientific Officer](https://reader036.vdocuments.us/reader036/viewer/2022062320/56649cc45503460f9498d852/html5/thumbnails/10.jpg)
Coenzyme Q10Coenzyme Q10
• Over 40 human clinical trials have been conducted in relation to cardiac parameters
• Meta-analysis on 8 studies showed significant effects for ejection fraction, cardiac output, stroke volume, end-diastolic volume (Soja, 1997)
• Although statin drugs are used to reduce cardiovascular morbidity and mortality, they consequently lower Co Q10 levels
• Over 40 human clinical trials have been conducted in relation to cardiac parameters
• Meta-analysis on 8 studies showed significant effects for ejection fraction, cardiac output, stroke volume, end-diastolic volume (Soja, 1997)
• Although statin drugs are used to reduce cardiovascular morbidity and mortality, they consequently lower Co Q10 levels
![Page 11: Dr. Peter J.E. Verdegem Chief Scientific Officer](https://reader036.vdocuments.us/reader036/viewer/2022062320/56649cc45503460f9498d852/html5/thumbnails/11.jpg)
Heart FunctionRole of Co-enzyme Q10
Heart FunctionRole of Co-enzyme Q10
• Limiting factor in electron transport chain
• Reduced concentration in myocyte
• A meta-analysis of 8 DBPC Q10 (60-200 mg/d) intervention trials in patients with NYHA class I-IV showed improved:– Ejection fraction: 1.37 SD– Stroke volume: 0.71 SD– Cardiac output: 0.61 SD– End diastolic volume: 1.23 SD
• Pre-operative Q10 supplementation (30-60 mg) in CABG patients improves post-operative cardiac output
• Limiting factor in electron transport chain
• Reduced concentration in myocyte
• A meta-analysis of 8 DBPC Q10 (60-200 mg/d) intervention trials in patients with NYHA class I-IV showed improved:– Ejection fraction: 1.37 SD– Stroke volume: 0.71 SD– Cardiac output: 0.61 SD– End diastolic volume: 1.23 SD
• Pre-operative Q10 supplementation (30-60 mg) in CABG patients improves post-operative cardiac output
Soja 1997: Molec. Aspects Med, Kamikawa 1985: Am J Cardiol, Tanaka 1982: Ann Thorac Surg. Folkers 1985: Proc. Natl Acad. Sci.
![Page 12: Dr. Peter J.E. Verdegem Chief Scientific Officer](https://reader036.vdocuments.us/reader036/viewer/2022062320/56649cc45503460f9498d852/html5/thumbnails/12.jpg)
L-CarnitineL-Carnitine
• Amino acid, although strictly speaking not
• Belongs more to the B vitamins
• Body can synthesize if enough iron, vitamin B1, vitamin B6, lysine, and methionine are present
• Dietary source is meat
• Amino acid, although strictly speaking not
• Belongs more to the B vitamins
• Body can synthesize if enough iron, vitamin B1, vitamin B6, lysine, and methionine are present
• Dietary source is meat
![Page 13: Dr. Peter J.E. Verdegem Chief Scientific Officer](https://reader036.vdocuments.us/reader036/viewer/2022062320/56649cc45503460f9498d852/html5/thumbnails/13.jpg)
L-CarnitineL-Carnitine
• Transfers long-chain fatty acids into the mitochondria
• Fuels the energy factories of the heart
• 70% of the heart energy comes from fatty acid breakdown
• In 1978, the first cardiovascular anti-ischemic effect was demonstrated and improvements in Electrocardiogram measurements
• Transfers long-chain fatty acids into the mitochondria
• Fuels the energy factories of the heart
• 70% of the heart energy comes from fatty acid breakdown
• In 1978, the first cardiovascular anti-ischemic effect was demonstrated and improvements in Electrocardiogram measurements
![Page 14: Dr. Peter J.E. Verdegem Chief Scientific Officer](https://reader036.vdocuments.us/reader036/viewer/2022062320/56649cc45503460f9498d852/html5/thumbnails/14.jpg)
MitochondriaMitochondria
![Page 15: Dr. Peter J.E. Verdegem Chief Scientific Officer](https://reader036.vdocuments.us/reader036/viewer/2022062320/56649cc45503460f9498d852/html5/thumbnails/15.jpg)
MitochondriaMitochondria
![Page 16: Dr. Peter J.E. Verdegem Chief Scientific Officer](https://reader036.vdocuments.us/reader036/viewer/2022062320/56649cc45503460f9498d852/html5/thumbnails/16.jpg)
Hawthorn (Crataegus Oxycantha)Hawthorn (Crataegus Oxycantha)
![Page 17: Dr. Peter J.E. Verdegem Chief Scientific Officer](https://reader036.vdocuments.us/reader036/viewer/2022062320/56649cc45503460f9498d852/html5/thumbnails/17.jpg)
Hawthorn (Crataegus Oxycantha)Hawthorn (Crataegus Oxycantha)
• Small shrubby tree with with bark
• Rich in flavonoids, vitamins, minerals and cardiotonic amines
• Exerts antioxidant effect on radicals inhibiting Angiotensin Converting Enzymes (ACEs)
• Vasodilation, blood flow to the heart
• Supports muscle contraction, cardiac rhythm
• Hawthorn is included in Germany’s Commission E Monograph for cardiovascular health
• Small shrubby tree with with bark
• Rich in flavonoids, vitamins, minerals and cardiotonic amines
• Exerts antioxidant effect on radicals inhibiting Angiotensin Converting Enzymes (ACEs)
• Vasodilation, blood flow to the heart
• Supports muscle contraction, cardiac rhythm
• Hawthorn is included in Germany’s Commission E Monograph for cardiovascular health
![Page 18: Dr. Peter J.E. Verdegem Chief Scientific Officer](https://reader036.vdocuments.us/reader036/viewer/2022062320/56649cc45503460f9498d852/html5/thumbnails/18.jpg)
Heart functionrole of HawthornHeart function
role of Hawthorn• Active ingredients
– flavonoids, polyphenols, triterpenic acids, vitamins, minerals and cardiotonic amines
• Mechanistic action
– inhibiting cellular phosphodiesterase, enhance intracellular cAMP and improve contractile force
– inhibiting the angiotensin converting enzyme activity, resulting in vasodilatation
– capturing free radicals
• Active ingredients
– flavonoids, polyphenols, triterpenic acids, vitamins, minerals and cardiotonic amines
• Mechanistic action
– inhibiting cellular phosphodiesterase, enhance intracellular cAMP and improve contractile force
– inhibiting the angiotensin converting enzyme activity, resulting in vasodilatation
– capturing free radicals
![Page 19: Dr. Peter J.E. Verdegem Chief Scientific Officer](https://reader036.vdocuments.us/reader036/viewer/2022062320/56649cc45503460f9498d852/html5/thumbnails/19.jpg)
Hawthorn trialsHawthorn trials
Study
Design
Subjects
Suppl.
Outcome
Weikl 1996
DB
136 CHF NYHA II
160 mg 8 weeks
Improved pressure heart rate and QOL Reduction Dyspnea
Weng 1984
DBPC 46 angina pectoris
100 mg 4 weeks
Reduction serum triglycerides and cholesterol
Schmidt 1994
DBPC
78 CHF NYHA II
600 mg 8 weeks
Improved exercise performance Reduction SBP, HR and pressure/rate
Study
Design
Subjects
Suppl.
Outcome
Weikl 1996
DB
136 CHF NYHA II
160 mg 8 weeks
Improved pressure heart rate and QOL Reduction Dyspnea
Weng 1984
DBPC 46 angina pectoris
100 mg 4 weeks
Reduction serum triglycerides and cholesterol
Schmidt 1994
DBPC
78 CHF NYHA II
600 mg 8 weeks
Improved exercise performance Reduction SBP, HR and pressure/rate
![Page 20: Dr. Peter J.E. Verdegem Chief Scientific Officer](https://reader036.vdocuments.us/reader036/viewer/2022062320/56649cc45503460f9498d852/html5/thumbnails/20.jpg)
TaurineTaurine
• Amino acid• Found in eggs, meat, fish and milk• Can be synthesized by the body, but is often too low• Vegetarians rely on body synthesis
• Amino acid• Found in eggs, meat, fish and milk• Can be synthesized by the body, but is often too low• Vegetarians rely on body synthesis
![Page 21: Dr. Peter J.E. Verdegem Chief Scientific Officer](https://reader036.vdocuments.us/reader036/viewer/2022062320/56649cc45503460f9498d852/html5/thumbnails/21.jpg)
TaurineTaurine
• High concentrations are found in heart muscle• Plays a role in electrolyte balance within the cells
(Calcium balance) and has an effect on cardiac muscle tissue cell membrane
• Prevents potassium leak from the heart muscle. This leak can result in dangerous cardiac arrhythmias
• Has antioxidant properties, protecting membrane lipids from peroxidation
• High concentrations are found in heart muscle• Plays a role in electrolyte balance within the cells
(Calcium balance) and has an effect on cardiac muscle tissue cell membrane
• Prevents potassium leak from the heart muscle. This leak can result in dangerous cardiac arrhythmias
• Has antioxidant properties, protecting membrane lipids from peroxidation
![Page 22: Dr. Peter J.E. Verdegem Chief Scientific Officer](https://reader036.vdocuments.us/reader036/viewer/2022062320/56649cc45503460f9498d852/html5/thumbnails/22.jpg)
Heart functionRole of TaurineHeart functionRole of Taurine
• Modulation of calcium transport
• Elevated taurine levels prevent calcium overload and are cardioprotective,
• Taurine deficiency reduces ventricular contractile force
• Ischaemic and CABG heart patients have reduced intracellular taurine levels.
• Modulation of calcium transport
• Elevated taurine levels prevent calcium overload and are cardioprotective,
• Taurine deficiency reduces ventricular contractile force
• Ischaemic and CABG heart patients have reduced intracellular taurine levels.
Schaffer 1994, Adv. Exp. Med Biol, Suleiman 1993: Br Heart J
Lake 1994: Adv. Exp. Med. Biol,
![Page 23: Dr. Peter J.E. Verdegem Chief Scientific Officer](https://reader036.vdocuments.us/reader036/viewer/2022062320/56649cc45503460f9498d852/html5/thumbnails/23.jpg)
Taurine intervention trialsTaurine intervention trials
Study
Design
Subjects
Suppl.
Outcome
Azuma 1985
DBPC cross-over
14 CHF patients
6 g/d 4 weeks
Improved NYHA Decrease pre-ejection period Reduced chest film abnormalities
Azuma 1992
DBPC
17 HF patients
3 g/d 6 weeks
Improved left ventricular function
Azuma 1983
Open study
24 CHF patients
2 g/d 4–8 weeks
Improved NYHA
Study
Design
Subjects
Suppl.
Outcome
Azuma 1985
DBPC cross-over
14 CHF patients
6 g/d 4 weeks
Improved NYHA Decrease pre-ejection period Reduced chest film abnormalities
Azuma 1992
DBPC
17 HF patients
3 g/d 6 weeks
Improved left ventricular function
Azuma 1983
Open study
24 CHF patients
2 g/d 4–8 weeks
Improved NYHA
![Page 24: Dr. Peter J.E. Verdegem Chief Scientific Officer](https://reader036.vdocuments.us/reader036/viewer/2022062320/56649cc45503460f9498d852/html5/thumbnails/24.jpg)
Cellular energy metabolismCellular energy metabolism
GlucoseFFA
Pyruvate
glycogenglucose 6P
glycolyse
ATP
Ca2+
Krebscycle
NADH2
FADH2
electron transport chain
O2
PCrADP
ATPCr
ADP
ATP
CKmyo
ATP ase
ATP
CKmito
ATP ase
ATP ase
ATP ase
actin/myosin
filaments
sarcoplasmicreticulum
mitochondrion
Calcium pumpand
Calcium channel
CKmyo
ADP
Ca2+
Lactate
Heart function
Taurine
CoQ10 Anti-oxidantsHawthorn
![Page 25: Dr. Peter J.E. Verdegem Chief Scientific Officer](https://reader036.vdocuments.us/reader036/viewer/2022062320/56649cc45503460f9498d852/html5/thumbnails/25.jpg)
Oxidative Stressrole of Vitamin EOxidative Stressrole of Vitamin E
• Vitamin E reduces susceptibility of LDL to oxidize.
• Long term use (> 2 years) of vitamin E supplements is associated with reduced risk of coronary heart disease:
– RR of 0.59 (95% confidence interval 0.38 - 0.91)
• DBPC Vitamin E (400 - 800 IU) intervention trial in 2002 CVD patients resulted in significant reduction of non fatal Myocard Infarcts with 77%
• Vitamin E reduces susceptibility of LDL to oxidize.
• Long term use (> 2 years) of vitamin E supplements is associated with reduced risk of coronary heart disease:
– RR of 0.59 (95% confidence interval 0.38 - 0.91)
• DBPC Vitamin E (400 - 800 IU) intervention trial in 2002 CVD patients resulted in significant reduction of non fatal Myocard Infarcts with 77%
Marangon 1999, Free Radic Biol Med, Stampfer 1993, NEJM (nurses health study), Stephans 1996, Lancet (CHAOS)
![Page 26: Dr. Peter J.E. Verdegem Chief Scientific Officer](https://reader036.vdocuments.us/reader036/viewer/2022062320/56649cc45503460f9498d852/html5/thumbnails/26.jpg)
Clinical Trial with MyoViveClinical Trial with MyoVive
• Performed in Toronto Canada with MyoVive
• Double blind placebo controlled trial
• 41 Congestive Heart Failure patients
• Performed in Toronto Canada with MyoVive
• Double blind placebo controlled trial
• 41 Congestive Heart Failure patients
![Page 27: Dr. Peter J.E. Verdegem Chief Scientific Officer](https://reader036.vdocuments.us/reader036/viewer/2022062320/56649cc45503460f9498d852/html5/thumbnails/27.jpg)
Clinical Trial with MyoViveClinical Trial with MyoVive
70
80
90
100
110
120
130
week 0 week 4 week 12
MyoVivePlacebo
Tim
e til
l exh
aust
ion
![Page 28: Dr. Peter J.E. Verdegem Chief Scientific Officer](https://reader036.vdocuments.us/reader036/viewer/2022062320/56649cc45503460f9498d852/html5/thumbnails/28.jpg)
Clinical Trial with MyoViveClinical Trial with MyoVive
![Page 29: Dr. Peter J.E. Verdegem Chief Scientific Officer](https://reader036.vdocuments.us/reader036/viewer/2022062320/56649cc45503460f9498d852/html5/thumbnails/29.jpg)
100110120130140150160170180190200
Baseline Post treatment
Clinical TrialClinical Trial
PlaceboMyoVive
End
dia
stol
ic v
olum
e
![Page 30: Dr. Peter J.E. Verdegem Chief Scientific Officer](https://reader036.vdocuments.us/reader036/viewer/2022062320/56649cc45503460f9498d852/html5/thumbnails/30.jpg)
• Conclusions:– Supplementation with carnitine, taurine and Co-Q10
resulted in higher myocardial levels of the ingredients
– These higher levels improve myocardial function
– After supplementation the time to exhaustion is larger
– Supplementation leads to a reduction of end diastolic volume
– This reduction improves prognosis for cardiac diseases
• Conclusions:– Supplementation with carnitine, taurine and Co-Q10
resulted in higher myocardial levels of the ingredients
– These higher levels improve myocardial function
– After supplementation the time to exhaustion is larger
– Supplementation leads to a reduction of end diastolic volume
– This reduction improves prognosis for cardiac diseases
Clinical Trial with MyoViveClinical Trial with MyoVive
![Page 31: Dr. Peter J.E. Verdegem Chief Scientific Officer](https://reader036.vdocuments.us/reader036/viewer/2022062320/56649cc45503460f9498d852/html5/thumbnails/31.jpg)