Nutrition Medicine in

 Dr. Melvyn A Sydney-Smith. KGSJ.
Adjunct Professor (Nutrition Medicine)
    RMIT University. Melbourne.
 Cardiovascular Disease ~ Prevalence in 2004-
In 2004-2005: 18% (3.5 million) of Australians reported
   having a long-term cardiovascular condition.
     hypertension ~ 11% (2.1 million)
     heart, stroke or vascular conditions ~ 3.8%
       28% reported angina,
       20% another ischaemic heart disease,
       12% a cerebrovascular disease,
       35% oedema and heart failure and
       27% reported an arterial disease capillaries
The number of Australians with cardiovascular disease
   declined from 4.3% in 2001, to 3.8% in 2004-05
Age-related prevalence of cardiovascular conditions ~

                               Age group (years)
          Source ABS, National Health Survey: Summary of Results, Australia,
                               2004-05 cat. no 4364.0
Reported prevalence of cardiovascular conditions,

 Source: ABS, National Aboriginal and Torres Strait Islander Health Survey,
                        2004-05, cat. no. 4715.0

   Cardiovascular Disease ~ mortality rate

Australian CVD mortality rates remain high ~ 110/1000
  though lower than USA, New Zealand and the UK.
                                Australian Bureau Statistics. 2004
    1970–72 AND 2002–04

Cardiovascular Disease ~ mortality rates

      Cardiovascular Disease ~ pathophysiology

 Atherothrombosis:
   most common trigger factor of a CVD event
      Atheromatous plaque erosion or rupture 
      Formation of a platelet-rich thrombus 
      Partial or complete vascular occlusion 
      Tissue ischaemia, damage and necrosis
                   Chapman MJ, Pharmacol Therapeut. 2007. 113(184-96)
    3 Major atherogenic mechanisms are:
      Dyslipidemia ~ Apo-lipoprotein balance
      Endothelial dysfunction

 Key players in all stages of atherothrombosis are:
    Vascular endothelial cells
       Prostacyclin production ~ from PGH2 by prostacyclin synthase
       Nitric Oxide synthesis ~ from Arginine by eNOS3
    Blood Platelets
       Atherogenesis ~
       Plaque progression ~ inflammation
       Thrombosis ~
    Leukocytes ~ monocytes & neutrophils & lymphocytes
       Inflammatory cascade ~ production of cytokines, free radicals
        and proinflammatory eicosanoids
    Fibroblasts & myoblasts ~
       cellular proliferation and intercellular matrix changes

Cardiovascular Disease ~ atherogenesis
   Pathophysiological mechanisms involved:
         Endothelial dysfunction
        Inflammation
        Oxidative stress
        Cholesterol accumulation
        Cellular apoptosis
        Extracellular matrix degeneration
   Accelerated by major risk factors:
        Dyslipidemia
        Hypertension
        Smoking
        Insulin resistance  obesity
            Chapman MJ, Pharmacol Therapeut. 2007. 113(184-96)
  Cardiovascular Disease ~ atherogenesis
 Multiple mechanisms contribute synergistically to atheromatous plaque
  development ~ cascading towards the disease phenotype
                        Chapman MJ, Pharmacol Therapeut. 2007. 113(184-96)

                   Endothelial Dysfunction


 Primary ~ preventive
  major disease reduction benefit occurs at this
  stage ~BUT~ only if therapy implemented
 Secondary
  morbidity and mortality benefits from therapy is
  well below that of primary prevention

      CardioVascular Diease: TREATMENT
 Focus of primary and secondary preventive therapy is to:
    Reduce cholesterol levels ~
       Statins ~ PLUS ~ Mediterranean diet
    Reduce platelet activity
       Aspirin ~ PLUS ~ Omega-3-Essential fatty Acids
    Reduce Inflammation ~
       Statins + aspirin
                                                   What about improving
    Improve Endothelial Dysfunction               cardiac & vascular cell
       Statins                                         metabolism?
    Control blood pressure
       ACE inhibitors, ACE receptor inhibitors
       chlorthiazides, calcium-channel blockers

              Cardiovascular Disease ~
Dyslipidemia is a major risk factor, related to CHD risk
 Cardiovascular Disease ~ Dyslipidemia
   LDL cholesterol reduction reportedly decreases:
       CVD events ~ including myocardial infarction and stroke
       CVD mortality ~ by about 30-40%
             Clinical Significance of Statin Pleiotropic Effects: Hypotheses Versus Evidence.
                                               Davidson MH. Circulation 2005;111;2280-2281

    Primary prevention ~ statin therapy
Baigent C, Keech A, et al. 2005. Lancet 366(9493).
   "Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data
   from 90,056 participants in 14 randomised trials of statins."
     The meta-analysis reported:
       12% proportional reduction in all-cause mortality per 1
        mmol/L reduction in LDL cholesterol
           RR 0.88, 95% CI 0.84-0.91; p<0.0001)
       19% reduction in coronary mortality
           RR 0.81, CI 0.76-0.85; p<0.0001), and
     non-significant reductions in:
       non-coronary vascular mortality
           RR 0.93, 0.83-1.03; p=0.2
       non-vascular mortality
           RR 0.95, 0.90-1.01; p=0.1

    Primary prevention ~ statin therapy
Thavendiranathan P. Bagai A, et al. 2006. Arch Intern Med. 166(21):2307.
         Primary Prevention of Cardiovascular Diseases With Statin Therapy:
                      A Meta-analysis of Randomized Controlled Trials.
         7 trials: 42 848 patients, 90% no CVD history, Mean follow-up 4.3 yrs
Statin therapy reduced the RR of:
     major coronary events, by 29.2%
         (95% CI, 16.7%-39.8%) (P<0.001)
     major cerebro-vascular events, 14.4%
         (95% CI, 2.8%-24.6%) (P=0.02)
     revascularizations 33.8%
         (95% CI, 19.6%-45.5%) (P<0.001)
Statin therapy produced non-significant reductions in:
     CHD mortality of 22.6%
        (95% CI, 0.56-1.08) (P=0.13)
     Overall mortality 8%
        (95% CI, 0.84-1.01) (P=0.09)

  Secondary prevention~ statin therapy
Maycock A, Muhlestein CA et al. 2002. J Am Coll Cardiol 40(10): 1777.
“Statin therapy is associated with reduced mortality across all age groups of
   individuals with significant coronary disease, including very elderly
 Mortality was decreased among statin users vs
   non-users in all age groups:
     >80 yrs: 29.5% non-users vs 8.5% users ~ HR 0.50, p =
     65-79 yrs: 18.7% non-users vs. 6.0% users ~HR 0.56,
     <65 yrs: 8.9% non-users vs. 3.1% users ~ HR 0.70, p =
NB: the Hazard Ratio for those <65 yrs age was actually NOT
  significant ~ contrary to the authors stated conclusions.

       CVD Therapy: omega-3-Fatty Acids
 Omega-3-EFAs 1000mg/day is also very effective
   Gizzi Prevenzione Trial reported:
     20% reduction in overall mortality
     30% reduction in cardiovascular deaths ~and~
     45% reduction in sudden death
                        Stone NJ. GISSI-Prevenzione Trial. Curr Cardiol Rep 2000; 2(5):445-451
   Omega-3-EFA therapy significantly prevents:
     cardiac arrhythmia ~and~
     Thrombotic disorders
                      Von Schacky C. The role of omega-3 fatty acids in cardiovascular disease.
                                                      Curr Atheroscler Rep 2003; 5(2):139-145
   Nambi V and Ballantyne CM. 2006). "Combination therapy with statins and omega-3 fatty acids.
                                                       Am J Cardiol 2006:98: 341-381

   Dyslipidemia and Antilipidemic Therapy
   Studer, M., M. Briel, et al. (2005). "Effect of Different Antilipidemic Agents and Diets on
            Mortality: A Systematic Review." Arch Intern Med. 165(7): 725-30.

 Compared with control groups, risk ratios for overall
  mortality were:
   0.77 for n-3 fatty acids (95% CI, 0.63-0.94)
   0.87 for statins (95% CI, 0.81-0.94)
   0.84 for resins (95% CI, 0.66-1.08)
   0.96 for niacin (95% CI, 0.86-1.08)
   0.97 for diet (95% CI, 0.91-1.04).
   1.00 for fibrates (95% CI, 0.91-1.11)

                   CVD ~ Omega-3-FAs & Statins
Nambi, V. and C. M. Ballantyne (2006). "Combination therapy with statins and omega-3 fatty acids.
                                Am J Cardiol 2006:98: 341-381.

 statin monotherapy is commonly insufficient to reduce
     Non-HDL cholesterol to recommended goals
     Triglyceride levels
 Statin + omega-3FAs consistently shown to be:
     effective, safe, and well-tolerated treatment
     provide additional lipid improvement without requiring
     additional laboratory tests
    do not increase risk for adverse muscle or liver effects.
 Patients with recent myocardial infarction may also benefit
  from this combination.

              Dyslipidemia: Statin & Niacin
Nicotinic acid is a more potent agent than fibrates for raising
  HDL-C, by up to 29% at recommended doses.
    It also substantially reduces triglycerides and LDL-C, and
    promotes a shift from small, dense LDL to larger, more
      buoyant LDL particles.
 nicotinic acid with a statin will produce a greater reduction in
  cardiovascular risk in patients with diabetes and metabolic
  syndrome than statin monotherapy alone.
 Nicotinic acid is safe for use in patients with diabetes, with
  no evidence of clinically relevant deterioration in glycaemic
  control at recommended doses (≤ 2g/day).
      Chapman, M. J., G. Assmann, et al. (2004). "Raising high-density lipoprotein cholesterol with
       reduction of cardiovascular risk: the role of nicotinic acid a position paper developed by the
        European Consensus Panel on HDL-C." Current Medical Research and Opinion 20: 1253.

                Dyslipidemia: Statin & Niacin
 Simvastatin (mean daily dose 13 ± 6 mg) and nicotinic acid
  (mean daily dose (2.4 ± 2.0 g) led to:
    26% increase in HDL-C, 38% reduction in triglycerides
     and 42% reduction in LDL-C.
    associated with a 90% fall in the frequency of major
     coronary events compared with placebo (p = 0.03) in
     patients with CHD,
    significant angiographic regression of stenosis by 0.4%
     on average, compared with progression of 3.9% on
     placebo (p < 0.001).
 Brown BG, Zhao XQ, Chait A, et al. Simvastatin and niacin, antioxidant vitamins, or the combination
                          for the prevention of coronary disease. N Engl J Med 2001;345:1583-92

 Taylor, A. J., L. E. Sullenberger, et al. (2004). "Arterial Biology for the Investigation of the Treatment
          Effects of Reducing Cholesterol (ARBITER) 2: A Double-Blind, Placebo-Controlled Study of
         Extended-Release Niacin on Atherosclerosis Progression in Secondary Prevention Patients
                                                      Treated With Statins." Circulation 110(23): 3512-7.
                    Secondary prevention
               Multiple Risk Factor Intervention
Multiple risk factor intervention trials show little overall benefit:
  statins, hypertensive agents, lifestyle counselling, AHA diet
   “these interventions may have small effects on levels of the major risk
      factors but very limited, impact on reducing mortality and morbidity.”
    the pooled odds ratios for total and CHD mortality were:
         0.96 (95% CI 0.92 to 1.01) for total mortality and
         0.96 (95% CI 0.89 to 1.04) for CHD mortality
         Net changes in systolic and diastolic blood pressure, were
          (weighted mean differences) -3.6 mmHg (95% CI -3.9 to -3.3
          mmHg), -2.8 mmHg (95% CI -2.9 to -2.6 mmHg) and and blood
          cholesterol -0.07 mMol/l (95% CI -0.8 to -0.06 mMol/l) respectively.
    Multiple risk factor interventions for primary prevention of coronary heart disease.
    Ebrahim S et al. Cochrane Database of Systematic Reviews: Reviews 2006 Issue
     Dyslipidemia: Red Yeast Rice ~ A Natural Statin
   Journoud, M. and P. J. H. Jones (2004). "Red yeast rice: a new hypolipidemic drug.“
                              Life Sciences 74(22): 2675.

    “Evidence shows that fermented red yeast rice:
  lowers cholesterol levels moderately compared to
                    other statin drugs,
                       ~but with~
the added advantage of causing less adverse effects.
   A review of the body of evidence surrounding the
 properties of red yeast rice underscores its potential
        as a new alternative to lipid level control.”

                   Dyslipidemia: A Natural Statin
   Zhao, S.-P., L. Liu, et al. (2003). "Effect of xuezhikang, a cholestin extract, on reflecting
  postprandial triglyceridemia after a high-fat meal in patients with coronary heart disease."
                                   Atherosclerosis. 168(2): 375.

 Xuezhikang (cholestin) significantly reduced:
   fasting serum total cholesterol (TC) by 20%
   low-density lipoprotein cholesterol (LDL-C) by 34%
   Triglycerides (TG) by 32% and
   ApoB by 27%) levels
 Significantly (p<0.001) elevated
   high-density lipoprotein cholesterol (HDL-C) by 18%
   apoA-I levels by 13%


                           CVD ~ Inflammation
    Gerard C & Rollins BJ. 2001. Chemokines and disease. Nature Immunology 2:108-15
Moutsopoulos, N. M. and P. N. Madianos (2006). "Low-Grade Inflammation in Chronic Infectious
      Diseases: Paradigm of Periodontal Infections." Ann NY Acad Sci 1088(1): 251-64
 Chronic inflammation is positively linked to CVD
     Elevated hs-CRP, proinflammatory cytokines {IL-6 and
      TNF-alpha} and chemokines
     Increased incidence of CVD in those with:
        Overt inflammatory conditions
               Autoimmune disease, renal disease, allergic disease, coeliac
                 disease, periodontal disease and inflammatory bowel
         Fatty infiltration of liver
               Persistent elevated GGT is predictive of metabolic syndrome
         insulin resistance  obesity
               Adipocyte production of cytokines and chemokines.

                 CVD ~ Inflammation
Recommended treatment is Aspirin therapy:
 Downregulates platelet activation by selectively inhibiting
  COX-1 activity 
 Reduces platelet TXA2 synthesis and decreases:
    Thrombogenesis
    Cytokine & chemokine release
    Pro-Inflammatory eicosanoid production
 Adverse effects of aspirin therapy are:
    Increased intestinal mucosal permeability
    Increased gastro-duodenal ulceration and bleeding
    Increased risk of haemorrhagic stroke
        CVD ~ Inflammation: aspirin therapy
   Njaman W, Miyauchi K, et al. (2006). "Impact of Aspirin Treatment on Long-Term Outcome
     (Over 10Years) After Percutaneous Coronary Intervention." Int Heart J 47(1): 37-45

 Aspirin therapy following PCI reportedly reduced:
   all cause mortality (10% versus 16.4%; P = 0.01) and
   cardiac death (3.7% versus 8.0%; P = 0.02) compared to
    other antiplatelet drugs.
 The hazard ratio (HR) was
    all cause mortality (HR, 0.49; 95%CI [0.29-0.80], P =
     0.005) and
    cardiac mortality (HR, 0.32; 95%CI [0.14-0.72], P =
            CVD ~ Inflammation: aspirin therapy
 Aspirin for the Primary Prevention of Cardiovascular Events in Women and Men: A Sex-Specific Meta-
analysis of Randomized Controlled Trials. Berger JS, Roncaglioni MC et al. 2006 JAMA 295(3): 306-13.
 Among 51 342 women, aspirin therapy was associated with:
      12% reduction in CV events, OR 0.88; 95% CI, 0.79-0.99; P =0.03
      17% reduction in stroke, OR 0.83; 95% CI, 0.70-0.97; P =0.02)
         reflecting lower ischemic stroke (OR, 0.76; 95% CI, 0.63-0.93;
           No significant effect on MI or cardiovascular mortality.
 Among 44 114 men, aspirin therapy was associated with:
      14% reduction in CV events (OR, 0.86; 95% CI, 0.78-0.94; P =0.01)
      32% reduction in MI (OR, 0.68; 95% CI, 0.54-0.86; P =0.001)
         No significant effect on stroke or cardiovascular mortality
 Aspirin Rx increased risk of bleeding:
      In women (OR, 1.68; 95% CI, 1.13-2.52; P =.01) and
      in men (OR, 1.72; 95% CI, 1.35-2.20; P<.001).
          CVD ~ Inflammation: combined therapy
  Hippisley-Cox J. & Copland C. 2005. "Effect of combinations of drugs on all cause mortality in
 patients with ischaemic heart disease: nested case-control analysis." BMJ 330(7499):1059-63.

 Drug combinations apparently exhibit synergistic effects:
     greatest reduction in all cause mortality were:
          statins, aspirin, and beta-blockers ~
           83% reduction (77 - 88% CI)
          statins, aspirin, B-blockers, and ACE inhibitors ~
           (75% reduction, 65% - 82% CI);
          statins, aspirin, and ACE inhibitors ~
           (71% reduction, 59% - 79%)

       What about Niacin and omega-3-EFAs?
            Enter “THE POLYPILL”

       Wald NJ and Law MR. 2003. A strategy to reduce cardiovascular disease
                    by more than 80%. BMJ. 326(7404): 1419.

                    One statin drug
    (atorvastatin 10 mg/d or simvastatin 40 mg/d)
           Three antihypertensive drugs
         thiazide, beta blocker, ACE inhibitor
                (at half standard dose)
                 Folic acid (0.8 mg/d)
                   Aspirin (75 mg/d)
 Estimated to reduce CHD events by 88% and stroke by 80%
 30% people above age 55 would gain 11 years, event-free
 8 – 15% would suffer medication adverse events
        CVD ~ Inflammation: periodontal therapy
Moutsopoulos, N. M. and P. N. Madianos (2006). "Low-Grade Inflammation in Chronic Infectious
      Diseases: Paradigm of Periodontal Infections." Ann NY Acad Sci 1088(1): 251-64.

 Periodontitis appears to be a primary risk factor for
  cardiovascular disease
 contributes to generation of a systemic inflammatory
    Elevated systemic inflammation markers:
          C-reactive protein, interleukin 6, haptoglobin & fibrinogen
     These markers are higher in periodontal patients with
      acute myocardial infarction (AMI) than in patients with
      AMI alone
     Intervention trials indicate periodontal therapy:
         improves endothelial function
        Reduces inflammatory markers
         CVD ~ Inflammation: periodontal therapy
Gebaraa EC, Pustiglioni AN et al. 2003. Propolis extract as an adjuvant to periodontal treatment.
                              Oral Health Prev Dent..1(1):29-35.

 Post-scaling subgingival propolis irrigation was
   more effective than conventional treatment ~ by
   both clinical and microbiological parameters
     Decreased anaerobic bacteria (p=0.007)
     Increased sites with low level P. gingivalis (p=0.005)
     Decreased sites with detectable yeasts (p=0.000)
     No increase in coagulase positive Staphylococci and
      Pseudomonas spp.
     Increased sites with probing depth (PD) < or = 3 mm
        CVD ~ Inflammation: periodontal therapy
English, H. K., A. R. Pack, et al. (2004). "The effects of manuka honey on plaque and gingivitis:
                        a pilot study." J Int Acad Periodontol 6(2): 63-7.

 Compared to the control group, manuka honey
  significantly reduced:
    mean dental plaque scores (0.99 down to 0.65; p=0.001),
    percentage of bleeding sites (48% down to 17%;
 Conclusion: These results indicate potential
  therapeutic role for manuka honey in the treatment
  of gingivitis and periodontal disease

Probably the most important factor in the
   promotion of cardiovascular disease
       Drexler, H. and B. Hornig (1999). "Endothelial Dysfunction in Human Disease.“
                                                         J Molec Cell Cardiol. 31: 51.
             CVD ~ Endothelial Dysfunction
       Napoli, C., W. C. Stanley, et al. (2007). Nutrition and cardiovascular disease:
     Putting a pathogenic framework into focus. Cardiovascular Research. 73(2): 253.

 Critical elements include:
   Genotype ~
      multiple polymorphic genes interact adversely with environment
      affecting lipid & glucose metabolism, cytokine & eicosanoid
       synthesis & production
   Intrauterine & perinatal nutrition & growth
   Dyslipidemia ~
      particularly LDL/HDL ratio & oxidised LDL
   Insulin Resistance and obesity
   Diet
      Many have been chosen ~ but few are effective
      Mediterranean diet most researched
         Lyon Heart Study, GISSI Preventiozone, DASH
   Exercise ~ Sedentary lifestyle vs regular exercise
   Smoking & environmental pollutants
            CVD ~ Genotypic disease
Multiple polymorphic genes interact adversely with
   affecting lipid & glucose metabolism, cytokine &
    eicosanoid synthesis & production

                 CVD ~ Genotypic disease

The human genome: is comprised of 46
22 autosomal pairs plus 2 sex chromosomes
The 3 billion base pairs of DNA contain
  about 30,000 - 40,000 protein-coding genes.
    •a much smaller number than predicted –
    •only twice as many as in the worm or fly
The coding regions are less than 5% of the genome
    •function of the remaining DNA is not clear
    •some chromosomes have a higher gene density
    than others.

Understanding Genetics: available from:
Accessed 12th July 2006.

                        Gene Polymorphism
Single nucleotide polymorphisms ~
 Single base-pair DNA differences observed
  between people
 simplest and most common form of DNA
  polymorphism ~
    frequency about of 1/1,000 base pairs
    In any individual, gene polymorphism is estimated
      to affect about 10% of the genome
 SNPs may cause disease if they affect expression
  of an enzyme-coding gene
    About 1000 monogenic diseases due to SNPs have
      been identified

           Jimenez-Sanchez G et al. 2001. Nature. 409:853-55

                      Gene Polymorphism

Each gene is composed of 2 alleles
  which may be:
    the same ~ homozygous ~ AA or aa
    different ~ heterozygous ~ Aa
However, there may be more than 2 allele
  variants {polymorphisms} ~
   e.g: APO E2, APO E3, APO E4
Thus a person’s APO E genotype may be:
      E2/E2, E2/E3, E2/E4
      E3/E3, E3/E4, E4/E4
  NB: 6 different genotypes

            Gene Polymorphism and Disease

Incidence of specific allele variants
   between populations often varies:
Thus the APO E4 gene ~
 Caucasian population
    mean frequency 15% ~
    North-South variance ~ 23% in
    Finland and 20% in Sweden down to
    8% in Italy
 Non-Caucasian populations
    About 30% in Africans (Nigeria)
    35% in Papua New Guinea
    5% in China
                      Multi-Genetic Disease
            Moreover, multiple polymorphisms interact to:
             modify nutrient demand and metabolism
                affect enzyme production and efficiency
             alter epigenetic regulatory mechanisms
                cytokines, hormones, sensor molecules and
                 transcription factors
                Ppars, MAP kinases, NF-Kappa-B
             modulate expression of other genes
                further alters metabolism and regulatory
             change responses to environmental factors
                nutrition, exercise, xenobiotics

Leads to development of disease phenotype
  Hypertension, coronary heart disease, Type 2 diabetes

               Multigenic disease: arteriosclerosis

Multiple polymorphisms that regulate expression and
  activity of genes involved in blood lipid regulation are
    Occur in 7 – 16% of population
          Apolipoproteins: Apo A-IV, Apo A, Apo B, Apo E
          Lipoprotein lipase
          Cholesterol ester transfer protein
     Affect cholesterol binding and clearance
     Promote hyperlipidaemia, arteriosclerotic disease and
     Alter responses to cholesterol reducing interventions
          Both dietary & pharmacological
          Confound epidemiological & interventional research

Knoblauch H, Bauerfeind A et al. Hum Molec Genet, 2002; 11(12):1477–85.

Other links have been identified ~
    Peroxisome proliferator activated receptor
        Regulates genes coding for inflammatory mediators, lipogenesis and
         glucose metabolism
        Gene variants contribute to cholesterol metabolism, insulin resistance &
    Sterol regulatory element-binding protein 1c (SREBP-1c)
       activates insulin-dependent increase in lipogenic gene expression
    Carbohydrate Response element Binding Protein (ChREBP)
       Glucose sensor that regulates glyco-lipid metabolism

Carbohydrate Response-Element Binding Protein
(ChREBP) ~ major gene-metabolic molecule
  Transcription factor coded for by a polymorphic gene
  Upregulates genes that code for lipogenesis
  Downregulates genes that code for glucose and lipid oxidation
  Activated by dietary carbohydrate (glucose & sucrose) and
  ChREBP activity inhibited/normalised by omega-3-EFA
                                                 Uyeda et al, 2002


Genotype is NOT an immutable
 prescription for disease
Multiple dietary, nutritional & lifestyle factors
  strongly influence:
    Nuclear & mitochondrial gene
    Promoter & suppressor codon activity
    Transcription factor production &
    Modulatory epigenetic molecules
Nutritional & lifestyle modification can
  counter a disease promoting genome
                              Kaput & Rodriguez, 2004
  Endothelial Dysfunction: Foetal & Perinatal Nutrition
  Atul Singhal. 2005. Endothelial dysfunction: role in obesity-related disorders and the early
           origins of CVD. Proceedings of the Nutrition Society (2005), 64, 15–22.

 Intrauterine growth retardation impairs vascular function
    Vascular function is impaired in infants born small-for-gestational
      age, but not in those of low birth weight due to prematurity
          Singhal A et al. 2001. Preterm birth, vascular function and risk factors for atherosclerosis.
                                                                              Lancet 358, 1159–1160
          Cheung YF et al. 2004. Relation of arterial stiffness with gestational age and birth weight.
                                                      Archives of Disease in Childhood 89, 217–221
    Vascular function is programmed in both preterm and full-term
      infants and the effects appear to be independent of size at birth.
 Faster postnatal growth has a detrimental programming
  effect on long-term vascular function.
   Endothelial Dysfunction: Environmental Pollution
   Bhatnagar, A. (2006). "Environmental Cardiology: Studying Mechanistic Links Between
                  Pollution and Heart Disease." Circ Res 99(7): 692-705.

 Many studies report that air pollution is associated with
  increased cardiovascular mortality
 significant relationships between particulate air pollution
  and ischemic heart disease, arrhythmias, and heart failure
  have been reported
 Exposures to arsenic, lead, cadmium, pollutant gases,
  solvents, and pesticides are also linked to increased
  incidence of cardiovascular disease.
 Urban diesel exhaust impairs vascular function and
               Mills NL, Tornqvist H., et al. 2005. Diesel Exhaust Inhalation Causes Vascular Dysfunction and
                                                Impaired Endogenous Fibrinolysis. Circulation 112(25): 3930-6.
         However, The major influence
on genomic an cardiovascular disease is probably
            the gross discrepancy
     between our human ancestral genome
      and the modern consumer-age diet

The human genome evolved under
  harsh selection conditions over a
  period of 3.5 million years ~
The spontaneous mutation rate for
  nuclear DNA is estimated at about
  0.5% per million years
Over the past 10,000 years, the human
  genome is calculated to have
  changed only 0.05% from our
  paleolithic ancestors ~
The human genome is now struggling to
  cope with the vastly different diet and
  lifestyle of the modern era
            Eaton SB. 2006. Proc Nutrit Soc. 65(1):1-6

The modern Homo sapiens genome evolved in northeast Africa about 200,000
        years ago ~ then migrated throughout the rest of the world
The first migration occurred following hominid decimation about 70,000 years
   ago  hunter-gatherer societies of the Middle East, Asia and Australia

Following the last Ice-Age 12,000 years ago, the birth of agriculture 10,000
   years ago  Settled lifestyle and increased population density
    ~ increased demand for intensive farming & animal
      husbandry – which occurred about 8,000 years ago
        ~ greater starch-yielding grain crops
        ~ increased gluten content in grains
        ~ altered fat content in animals from supplemental feeding
    ~ Industrial revolution altered food supply even further
        ~ farming monoculture developed
        ~ increased dependence on grains
        ~ refined sugars became more accessible
        ~ increased fat and trans-fat intake
        ~ increased omega-6/omega-3 EFA ratio
               Bradshaw Foundation.
                  Paleolithic diet:   Modern Diet
Protein ~           30-40%               10-20%
Carbohydrates ~     35%                  60-70%
    sugars ~        2-3%                 15%
Fats ~              30-35%               30-35%
Saturated fats ~    7.5%                 15-30%
Trans-fat           < 1%                 5-10% of fats
Omega-6/omega-3 ~    2:1                 10-20:1

Before European contact, hunter-gatherer population diets
  approximated the Paleolithic Diet
   ~ Australian Aborigines ~ migrated 50,000 yrs ago and isolated
     until 1778
     Diet based on wild game, seafood, nuts, seeds, yams & greens
   ~ Pacific Islands ~ Fiji 1500 BC, Samoa & Cook Islands      200
     BC, Hawaii 600 AD,
   ~ New Zealand about 1250 AD
     Diet was based on seafood, poultry, pig + taro, cassava, various
     greens, tropical fruits, nuts, seeds and coconut

Hunter-gatherer diets.
Analysis of dietary intake of 229 Hunter-Gatherer populations
around the world showed median animal food intakes of
66 – 75% and plant food intakes 26 – 35% of total energy.
Cordain L, Eaton SB et al. 2002. EJCN.56,Suppl 1:S42–S52.

                                               Animal food   Plant food
                                                  (%)           (%)
            Ache (Paraguay) 25S                     78          22
             !Kung (Africa) 20S                     68          32
       Aborigines (Arnhem Land) 12S                 77          23
           Anbarra (Australia) 12S                  75          25
             Hiwi (Venezuela) 6N                    75          25
           Onge (Andaman Is) 12N                    79          21
Traditional diet improves chronic
In full-blood Aborigines with CHD,
   diabetes and hypertension,
   reversion for 7 weeks to a
   “traditional” diet resulted in:
    ~ mean wt loss of 8kg over 7
    ~ reduced blood pressure
    ~ reduced fasting insulin &       The traditional diet
       glucose                        consisted of:
    ~ improved glucose and insulin    ~ 64% protein,
       responses on GTT               ~ 13% fat and
                                      ~ 23% low-GI/GL CHOs
    ~ reduced triglyceride and VLDL   ~ 1200 Cal/person/day
                                          K O'Dea. 1984. Diabetes,
    ~ reduction or cessation of                    33(6): 596-603.

              Genes, Diet and Disease
The broad perspective of human metabolic and archeological
    data suggests that human genes are adapted to a nutrient
    intake that approximates that of the Paleolithic Diet
Genomic research has identified multiple gene-regulated
    transcription binding proteins that are:
    a) responsive to dietary lipid and CHO intake and
    b) propel metabolism towards common disease
      CHD, Hypertension, Insulin Resistance, Diabetes etc.
Individual gene variants have also been identified that affect
   a) disease development and
   b) response to nutritional and pharmacological therapy
            DIET, Insulin Resistance & Obesity
        Napoli, C., W. C. Stanley, et al. (2007). Nutrition and cardiovascular disease:
      Putting a pathogenic framework into focus. Cardiovascular Research. 73(2): 253.

 Improper diet and lack of exercise are the major
  contributory factors in development of obesity
 Obesity promotes atherogenesis via two related
   insulin resistance
      hyperinsulinaemia and elevated blood glucose
      endothelial dysfunction
   Promotes low-grade chronic inflammation
      elevated TNF-alpha and other cytokines
     ~ IL6, PAF and various chemokines
                Endothelial Dysfunction: Obesity
  Hotamisligil GS. 2006. Inflammation and metabolic disorders. NATURE. 444(14):860-67.
 Metabolic and immune response pathways have been
  evolutionarily conserved throughout the species
   Immune activity and metabolic regulation are highly integrated and
   This interface acts as a central homeostatic mechanism
   Dysfunction promotes obesity and leads to a cluster of chronic
    metabolic disorders

 Atherogenesis ~ Endothelial Dysfunction: Diet
 Multiple dietary factors and nutrient balances reportedly
    affect endothelial function, inflammation and blood lipids:
      Saturate fat vs unsaturated fat intake
      Omega-6 vs omega-3 unsaturated fat intake
      Dietary carbohydrate load
      Carbohydrate vs fat intake
      Dietary antioxidant and polyphenol intake
      Dietary fibre intake
      Dietary fat vs polyphenol vs carbohydrate intake

Cordain, L., S. B. Eaton, et al. (2005). "Origins and evolution of the Western diet: health implications
   for the 21st century." Am J Clin Nutr. 81(2): 341-54.
Giugliano, D., A. Ceriello, et al. (2006). "The Effects of Diet on Inflammation: Emphasis on the
   Metabolic Syndrome." J Am Coll Cardiol. 48(4): 677.
 Kopp, W. (2006). The atherogenic potential of dietary carbohydrate. Preventive Medicine. 42(5): 336.
       The Assessment and Management of                                          65
 Cardiovascular Risk. Evidence-based Best Practice
                    New Zealand Guidelines Group, December 2003.
1) Enjoy three meals a day, selecting from dishes that encourage you to eat
    plant foods and fish, with little or no dairy fat, meat fat or deep fried
2) Choose fruits and/or vegetables at every meal and most snacks.
3) Select whole grains, whole grain breads, or high fibre breakfast cereals
    in place of white bread and low fibre varieties at most meals and snacks
4) Include fish, or dried peas, beans and soy products, or a small serving of
    lean meat or skinned poultry, at one or two meals each day
5) Choose low fat milk, low fat milk products, soy or legume products every
6) Use small amounts of oil, margarine, nuts or seeds
7) Drink plenty of fluids each day, particularly water, and limit sugar-
    sweetened drinks and alcohol
8) Use only small amounts of total fats and oils, sugar and salt when
    cooking and preparing meals, snacks, or drinks. Choose ready-prepared
    foods low in these ingredients
9) Mostly avoid or rarely include butter, deep-fried and fatty foods, and only
    occasionally choose sweet bakery products
       Atherogenesis ~ Endothelial Dysfunction: Diet
           Parikh P, McDaniel MC et al. 2005. Diets and Cardiovascular Disease.
                           J Am Coll Cardiol 2005;45:1379–87
 Low-Fat diet                                 Low-Carbohydrate Diet
    Difficult to achieve                            Short-term weight loss
    Promotes Insulin Resistance                     Long-term effects on CVD
    No impact on mortality                            unknown
                                                     Initiate decreased energy intake &
                                                       weight loss
 Very-Low-Fat Diet
                                               Mediterranean Diet
    May decrease cardiac events
                                                     Secondary prevention
    Concern about applicability and
     sustainability                                  Prevention of sudden cardiac death
                                                     Healthy overall approach to dieting
 Low Glycemic Index Diet                            Long-term sustainability
    Unproven effects on CVD                   DASH
    Initiate reduced intake of                      Decreased hypertension ~
     energy-dense CHOs and                             by 5.5/3.3mm
    initiate weight loss                            Similar to Mediterranean Diet
                                                   Stern et al.                      Yancy et al.
     Low CHO Diet                 Foster et al.
                                                   Ann Int Med
                                                                     Brehm et al
                                                                                     Ann Int Med,
    and Weight Loss               NEJM. 2003                         JCEM. 2003
                                                      2004                              2004

Length of Trial                      12 mo            12 mo             6 mo             6 mo
Low-CHO: baseline weight (kg)        99 + 20         130 + 23           91 + 8         97 + 19

                                      -4 + 7           -5 + 9           -9 + 1          -12 + 2
Low-CHO: diet weight change (%)

Low-fat baseline weight (kg)         98 + 16         132 + 27           92 + 6         98 + 15
Low-fat diet weight change (%)        -3 + 6           -3 + 8           4+1             -7 + 2
p value (between groups)              0.26             0.195           <0.001           <0.001
Parikh P, McDaniel MC et al. Diets and Cardiovascular Disease. J Am Coll Cardiol 2005;45:1379–87
Low GI or GL diets inconclusive. Parikh P et al. J Am Coll Cardiol 2005;45:1379–87   68

CHD Risk & DIET: Mediterranean Diet ~
        Endothelial Dysfunction: Optimal Diet

What is the optimal diet?
   Maintain low-moderate Glycemic Index and Glycemic
    Load ~
   Optimise Antioxidant & fibre intake ~ fruit & vegetables
   Increase Essential Fatty Acid intake & omega-3/omega-6
    balance ~
   Maintain protein intake ~ fish, nuts/seeds, lean meat,
    cheese, legumes & wholegrains
   Reduce saturated fat & trans-fat intake ~
   Reduce calorie intake ~ ? 20-30% reduction promotes
    antiaging effect

Endothelial Dysfunction: Diet


                Cardiovascular Disease ~
    Endothelial Dysfunction, Nitric Oxide and Arginine
     Wu G and Meininger CJ. 2000. Arginine Nutrition and Cardiovascular Function.
                          J. Nutr. 130: 2626–2629, 2000

 Nitric Oxide ~ is a major mediator in endothelial function:
    Produced in vascular endothelial cells by NO-synthetase
     from arginine
    NO is a vital anti-atherogenic molecule that:
        Inhibits atherogenesis
        Enhances vasodilator activity
    Reduced NO production:
        is a measure of impaired endothelial health and
        directly facilitates development of atherosclerosis
    eNOS activity & NO production can be increased by:
        High antioxidant intake ~ particularly ascorbate
        Arginine therapy
        Statin therapy
            Cardiovascular Disease ~
        Arginine, NO and endothelial dysfunction
 Compelling evidence shows that Arginine:
   reverses endothelial dysfunction associated with major
    cardiovascular risk factors:
      hypercholesterolemia, smoking, hypertension,
       diabetes, obesity/insulin resistance and aging
   ameliorates many common cardiovascular disorders
      coronary and peripheral arterial disease, heart failure,
       and ischemia/reperfusion injury
   Increasing dietary arginine & ascorbate intake increases
    endothelial NO production

        Wu G and Meininger CJ. Arginine Nutrition and Cardiovascular Function.
                                                 J. Nutr. 130: 2626–2629, 2000
 Cardiovascular Disease ~
Arginine and endothelial dysfunction

    CVD Therapy: Antioxidants ~ Vitamin C
Vitamin C:
   Epidemiological study reported development of CHD in
    males correlated inversely with Vit C status
       Nyyssonen K, Parviainen MT et al. Vitamin C deficiency and risk of myocardial infarction:
                                                               BMJ 1997; 314(7081):634-638.

   Vit C was not useful in secondary prevention of CHD
                    MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in
                                 20,536 high-risk individuals: Lancet 2002; 360(9326):23-33

   Nurses Health Study showed significantly reduced CHD
    event risk with ascorbate supplement use
       Osganian SK, Stampfer MJ et al. Vitamin C and risk of coronary heart disease in women.
                                                        J Am Coll Cardiol 2003; 42(2):246-252

 CVD Therapy: Antioxidants ~ Vitamin E
 Vitamin E:
   Regulates endothelial cell proliferation
   Inhibits platelet adhesion & activation
   Protects against oxidation ~ particularly LDL
      BUT must be natural mixed tocopherols ~and~ high
           dose > 400 ~ 800 IU/day
            -tocopherol markedly reduces -tocopherol level
            -tocopherol is the more effective endovascular
             protective agent
              reduces LDL cholesterol
              Neutralises peroxynitrite damage
 Singh, I., A. H. Turner, et al. (2005). Effects of gamma-tocopherol supplementation on thrombotic risk factors and
                                                       measures of oxidative stress. Asia Pacific J Clin Nutri.14: S48.
  Dietrich, M., M. G. Traber, et al. (2006). Does [Gamma]-tocopherol play a role in the primary prevention of heart
                                                                   disease and cancer? A review. JACN. 25(4): 292.

   CVD Therapy: Antioxidants ~ Vitamin E
 Contemporary studies indicate Vit E therapy:
   Has no impact on CVD occurrence or outcome ~OR~
   May promote CCF occurrence and mortality
     Lonn E, Bosch J, et al. (2005). "Effects of long-term vitamin E supplementation on cardiovascular
                               events and cancer: a randomized controlled trial." JAMA. 293(11): 1338.
 Most Vit E studies are heavily flawed:
   No monitoring of oxidative stress and markers of
    vascular response,
   No monitoring of vitamin E levels.
   Short duration and suboptimal dosages of vitamin E,
   Suppression of gamma-tocopherol by alpha-tocopherol,
   Unbalanced Vitamin E supplementation
   Inappropriate administration relative to meal ingestion,
Robinson, I., D. G. de Serna, et al. (2006). "Vitamin E in humans: an explanation of clinical trial failure.
                                                                    Endocrine Practice. 12(5): 576-82 .

         CVD Therapy: Antioxidants : Selenium
Useful antioxidants:
 Selenium: works synergistically with Vit E
   protects cell membrane from oxidative damage
   Selenium concentrations were inversely associated with
      coronary heart disease risk in observational studies
             Flores-Mateo, G., A. Navas-Acien, et al. (2006). Selenium and coronary heart disease:
                                                     a meta-analysis. Am J Clin Nutr 84(4): 762-73.
   Women living in the community who have higher serum
      selenium are at a lower risk of death HR: 0.71, 95% CI
 Ray AL, Semba RD, et al. 2006. Low serum selenium and total carotenoids predict mortality among
  older women living in the community: the women's health and aging studies. J Nutr 136(1): 172-6.

      CVD Therapy: Antioxidants ~ Flavonoids
 Bioflavonoids (quercetin & hesperidin) and polyphenols) :
     increase tissue antioxidant capacity
     increase anti-inflammatory activity
     decrease platelet activation ~and~
     enhance vascular endothelial function
     intake inversely associated with cardiovascular disease
                 Bucki R, Pastore JJ, et al. 2003. Flavonoid inhibition of platelet procoagulant activity
                                     and phosphoinositide synthesis. J Thromb Haemost 1(8): 1820-8.
    Geleijnse, J. M., L. J. Launer, et al. (2002). "Inverse association of tea and flavonoid intakes with
                   incident myocardial infarction: the Rotterdam Study." Am J Clin Nutr 75(5): 880-6.
 Perez-Vizcaino, F., J. Duarte, et al. (2006). "Endothelial function and cardiovascular disease: effects
                                of quercetin and wine polyphenols." Free Radic Res 40(10): 1054-65.
                     CVD Therapy: Antioxidants
                        Cocoa & Chocolate
Engler, M. B. and M. M. Engler (2006). "The emerging role of flavonoid-rich cocoa and chocolate in
   cardiovascular health and disease." Nutr Rev 64(3): 109-18.
 Cocoa and chocolate are rich sources of antioxidant
    flavonoids with beneficial cardiovascular properties.
      Favorable physiological effects include:
           antioxidant activity,
           Vasodilation & blood pressure reduction,
           reduced platelet activity
           Increased anti-inflammatory activity
           Improved isulin sensitivity
 Increasing evidence, experimental & clinical, suggest an
    important role for these high-flavanol-containing foods in
    heart and vascular protection.
              CVD Treatment: Coenzyme Q10
  Tran MT, Mitchell TM, et al. 2001. Role of coenzyme Q10 in chronic heart failure, angina,
                    and hypertension. Pharmacotherapy 21(7): 797-806.

CoQ10 is an essential lipid-soluble element of the Electron-
  Transport Chain
   Mitochondrial antioxidant & electron transfer molecule
     Essential to mitochondrial oxidative activity ~and~
     myocardial contractility
   Improves outcomes in cardiomyopathy & CCF
     Increases ejection fraction, stroke volume, cardiac
      output and exercise tolerance
   Co-Q10 level is reduced by statin therapy
              Sander S, Coleman CI, et al. 2006. The impact of coenzyme Q10 on systolic function
                                     in patients with chronic heart failure. J Card Fail 12(6): 464-72.
                    Chew GT. and Watts GF. 2004. Coenzyme Q10 and diabetic endotheliopathy:
                      oxidative stress and the 'recoupling hypothesis'. Quart J Med. 97(8): 537-48.
            CVD Treatment: alpha-Lipoic acid
           Jones W, Li X, et al. 2002. Uptake, recycling, and antioxidant actions of
           alpha-lipoic acid in endothelial cells. Free Radic Biol Med 33(1): 83-93

 Lipoic acid: sulphur-containing antioxidant
    Essential to cell membrane integrity & function
       particularly electrical conductance
    Stimulates glutathione synthesis
    enhances endothelial antioxidant defence and function
        recycles dehydroascorbic acid to ascorbate,
        decreases ROS generated by redox cycling
        generates nitric oxide
    restores mitochondrial aldehyde dehydrogenase activity
     thereby improving nitrate tolerance
   Wenzel P, Hink U, et al. 2007. Role of reduced lipoic acid in the redox regulation of mitochondrial
        aldehyde dehydrogenase (ALDH-2) activity. Implications for mitochondrial oxidative stress
                                                    and nitrate tolerance. J Biol Chem 282(1):792-9.
            CVD Treatment: alpha-Lipoic acid
  Sethumadhavan, S. and P. Chinnakannu (2006). "L-carnitine and alpha-lipoic acid improve
    age-associated decline in mitochondrial respiratory chain activity of rat heart muscle."
                        J Gerontol A Biol Sci Med Sci 61(7): 650-9.

 Progressive mitochondrial structural damage and
  loss of integrity occurs with aging 
    impairs cellular energy genesis, reducing activity of:
         TCA cycle enzymes and
         electron transport chain complexes
 Combined carnitine/lipoic acid treatment:
   raises mitochondrial energy producing capacity
   reverses age-related mitochondrial enzyme decline
   protects mitochondria from aging
                        CVD Treatment: Garlic
      Rahman K. and Lowe GM. 2006. Garlic and cardiovascular disease: a critical review.
                            J Nutr 136(3 Suppl): 736S-40S.
 Epidemiologic studies show an inverse correlation between
  garlic consumption and progression of cardiovascular
 Numerous in vitro studies report that garlic
      inhibits enzymes involved in lipid synthesis,
      decreases platelet aggregation,
      prevents lipid peroxidation of oxidized erythrocytes and LDL,
      increases antioxidant status,
      inhibits angiotension-converting enzyme.
 44% of clinical studies report positive effects from garlic:
      reduces cholesterol,
      inhibits platelet aggregation,
      reduces blood pressure,
      increases antioxidant status.

                        CVD Treatment: Garlic
 Borek C. 2006. Garlic reduces dementia and heart-disease risk. J Nutr 136(3 Suppl): 810S-2S.

 Aged Garlic Extract (AGE) reportedly:
   scavenges oxidants,
   increases superoxide dismutase, catalase, glutathione
    peroxidase, and glutathione levels,
   inhibits lipid peroxidation and inflammatory
   reduces cholesterol synthesis
      by inhibiting 3-hydroxy-3-methylglutaryl-CoA
      effect is additive with statins in its action.
                     CVD Treatment: Garlic
   Rahman K. and Lowe GM. 2006. Garlic and cardiovascular disease: a critical review.
                         J Nutr 136(3 Suppl): 736S-40S.

 Over 50% of clinical trials report negative results,
  possibly due to:
    usage of different garlic preparations,
    unknown active constituents and their bioavalability,
    inadequate randomization,
    selection of inappropriate subjects,
    short duration of trials.
                  CVD Therapy:
      Vitamins B6, Folate, B12 & Betaine
These nutrients reduce serum homocysteine level
   Homocysteine > 12mm/L is an independent risk factor for
    vascular disease ~ smoking & high lipids.
            Graham IM, Daly LE et al. Plasma homocysteine as a risk factor for vascular disease.
                                                                JAMA 1997; 277(22):1775-1781.
   Elevated homocysteine impairs endothelial function
   Endothelial dysfunction responds to folate therapy
    independent of homocysteine level
     ? By maintaining tetrahydrobiopterin activity
   Vit B6 insufficiency impairs endothelial function
    Moat SJ, Lang D et al. Folate, homocysteine, endothelial function and cardiovascular disease.
                                                             J Nutr Biochem 2004; 15(2):64-79
                    CVD Therapy: Niacin
      Elam MB, Humminghake DB et al. ADMIT study. JAMA. 2000. 284:1263-70

 Niacin therapy
   Increased HDL cholesterol by 29%
   Reduced triglycerides by about 25% ~and~
   Reduced LDL cholesterol by about 9%
   was safe for use in patients with diabetes
 Use the Inositol Hexaniacinate form
   Minimises risk of niacin reaction
   With phosphatidylcholine, hexaniacinate can optimise
    bile-salt production & cholesterol excretion
                  Goldberg AC. 2004. A meta-analysis of randomized controlled studies on the
                       effects of Extended-Release niacin in women. Am J Cardiol. 94(1):121.

   Nutrient Therapy in Vascular Disease
 Mineral therapy:
   Magnesium & Potassium:
     improve myocardial metabolism ~and~ inhibits
      arrhythmia ~and~ lowers blood pressure
   Calcium: essential for myocardial contraction ~and~
    assists in regulating BP
   Zinc: essential for mitochondrial function ~and~
    DNA/RNA repair
   Chromium: essential for Glucose Tolerance Factor
   Vanadium: Stabilises blood sugar & reduces blood lipids

      Nutrient Therapy in Vascular Disease
 Cardiovascular disease arises as a result of the interaction
  between multiple related causal factors
    Good research into the role of many of these factors and
     the management thereof remains woefully inadequate
        broad spectrum pharmacotherapy is NOT a good
        option ~ particularly for primary prevention
    Good management should seek to remediate all causal
     factors identified in the patient, utilising an integrated
     regimen of:
       Nutrient supplementation
       Targeted pharmacotherapy

  Nutrient Therapy in Vascular Disease
Effective management needs to be systematic ~
  our protocol is to assess and optimise:
            Antioxidant capacity
            Essential Fatty Acid balance
            Bowel dysbiosis
            Specific therapy
            Neurotransmitter balance
            Hepatic detoxification
            Hormonal balance

 Thank you for your attention
Please feel free to speak to me
      during the breaks

             Don’t forget ~
       enjoy your daily Polymeal
 Grilled salmon with onion & garlic
    Served with sauce of: tomato paste, garlic, coriander
 Salad: lettuce, purslane, celery, cucumber, tomato,
  capsicum, mushroom, avocado, tofu & almonds
    Dressing: olive oil, garlic & vinegar
 Green tea served before the meal
 Dessert: blueberries, strawberries with chocolate sauce
  (made with soy-milk & dark chocolate)
 After-dinner drinks: Cabernet sauvignon 1glass
    Plus 1 Poly-nutrient pill

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