Nutrition and nutraceuticals used to

treat and prevent HYPERTENSIONHYPERTENSION

Presented by Dr Craige Golding

MBChB (Cum Laude) FCP(SA)Specialist Physician

ABAARM: American academy board certified anti-aging physicianFAAFM: Fellowship in anti-aging and functional medicine

Dr Craige Golding MBChB (Cum Laude) FCP(SA)

Specialist PhysicianABAARM: American academy board certified anti-aging physician

FAAFM: Fellowship in anti-aging and functional medicine

Dr Golding is a Specialist Physician in private practice at the Rosebank Clinic, Johannesburg. He is a fellow of the SA College of Physicians. Dr Golding has a keen interest in preventative and integrative medicine and has Board Certification in Anti-aging Medicine from the American Board of Anti-aging Medicine. He has completed his Fellowship in Anti-aging medicine through the American Academy of Anti-aging Medicine. Prior to completing his Fellowship as a physisian, Dr Golding was awarded the Akromed prize for the best student in Pharmacology, Horrace Wells medal for the best Anaesthetics student & the Maybaker prize for the best undergraduate student in Psychiatry.

HYPERTENSION AND OXIDATIVE STRESS

• Oxidative stress with an imbalance between ROS and the antioxidant defense mechanisms may contribute to the etiology of hypertension, its initiation, maintenance, pathogenesis, pathophysiology, and cardiovascular complications

HYPERTENSION AND OXIDATIVE STRESS

• Essential hypertension and salt sensitive HT

• Diabetes and hypertension• Lead induced hypertension• Uremic hypertension• Cyclosporin induced hypertension• Pre-eclampsia• Nutritional induced (high fat and

unrefined carbohydrates) hypertension

HYPERTENSION AND OXIDATIVE STRESS ROS IN

HYPERTENSION• ROS has direct action on endothelial cells with

structural and functional damage• Degradation of NO by ROS• Effects of eicosanoid metabolism in

endothelial cell• Oxidative modification of LDL-c (oxLDL)• Hyperglycemia, hyperinsulinaemia• Increased fatty acid mobilization• Increased catecholamines• Angiotensin II increases O2- via NADPH

oxidase

IMPAIRED DEFENSE TO ROS

• Increased lipofuscin, increased lipid peroxidation

• Increased malondialdehyde, increased lipid peroxidation

• SOD decreased in erythrocytes and plasma

• Glutathione peroxidase decreased• Decreased vit A• Decreased Vit c

IMPAIRED DEFENSE TO ROS CONTINUED

• Decreased vit e• Decreased NO• Increased O2- by PMN and increased

H2O2• Decreased PUFA in RBC membrane• Decreased glutathione• Decreased selenium

Lifestyle changes and SBP metanalysis of clinical diet

trials • Intervention reduction in SBP

(mmhg) • ---------------- ------------------------------- • Mg++ 0-1• Ca++ 2• K+ 4• Decreasing ETOH 4 • Fish oil 6• Lowering Na+ 6• Lowering weight 8• Exercise 10

Lifestyle modifications and withdrawal of antihypertensive

drugs, J Hypertension 1988;6:431-6

• Between 15 and 60% of hypertensive patients withdrawn from antihypertensive drugs remain normotensive for 9 to 36 months on strict lifestyle modifcations of nutrition, weight loss, exercise, alcohol and sodium restriction,etc

PROTEIN, Current atherosclerosis reports 2000:2;521-528 ;Jama 1996:274:1598-1603

• Observational epidemiologic studies indicate a high protein intake reduces BP (non-animal>vs animal protein) in numerous populations

• Daily intake recommended1-1.5g/kg/day depending on many factors

• Intermap study : inverse relationship of BP with total protein intake and non-animal protein

Protein (continued)

• Intersalt study : 10020 subjects, worldwide had lower blood pressure (3/2.5mm hg) with dietary protein >30% above mean vs those 30% below mean (81g vs 44g/day)

• Mechanisms : ACEI, reduces SNS (Epeinephrine/NE, natriuresis, inhibits tyrosine kinase, reduces aldosterone, reduces superoxide ion

SOY PROTEIN , Biochem Pharmacol 2000;60:1-5

• Lowers BP and increases arterial compliance

• Lowers LDL-c (7%), TC (6%), LDL oxidation

• Consume 25g/day• Contains : isoflavones, amino acids,

saponins, phytic acid, trypsin inhibitors, fiber, globulins, genistein/daidzen

Whey protein, J dairy Sci 2000;83:255-263

• Significant reduction in BP in animal and human studies

• 30-150mg/kg of ion exchange hydrolyzed whey protein isolate reduces MAP 10-18% for 24 hours (p<0.05)

• Must be hydrolyzed to be effective• Act as ACEI• 20 men given 200ml whey protein BID x

8 weeks decreased SBP significantly (p<0.05)

Omega 3 PUFA : circ 1992;88:523-33 ; Hypertension

1998;32;710-717• Meta-analysis 31 studies fishoil and BP

showed dose related effect in mild hypertension only :

• < 4g/d : no change in BP• 4-7g/d lowered BP by 1.6-2.9mm hg• >15g/day lowered BP by 5.8-8.1mm hg• One percent increase in adipose tissue

alpha-linoleic acid content reduced SBP, DBP and MAP by 5mm hg

OMEGA 3 PUFA, current atherosclerosis reports

2000:2:508-515; Hypertension 1999;34:253-60

• Fish 3 x/week lowers BP (herring, haddock, atlantic salmon, trout)

• Fish or fishoil + weight loss is additive to lower BP

• DHA better to lower BP• Reduced ALA conversion to EPA and

DHA (increased linoleic acid in diet omega 6, increased TSFA and TFA in the diet, alcohol)

OMEGA 6 FATTY ACIDS

• LA, GLA, DGLA,AA, CLA• GLA ->DGLA -> PGE1 and PGI2 cause

vasodilation• GLA blocks stress induced

hypertension• (increases PGE1, PGI2, decreases

aldosterone, decreases adrenal AT1 receptor density / affinity)

• Neurohormonal regulation (SNS, RAAS)-central + peripheral

MUFA (olive oil), arch IM 2000;160: 837-842

• 23 hypertensive subjects studied for 6 months.

• Significant reduction in BP 8/6mm hg in extra virgin olive oil group, p<0.05 and >0.01

• Reduces need for antihypertensive drugs in 48% vs 4% in control group

• Reduces BP in type II DM• No reduction of BP in normotensive, or non-

diabetics

MUFA (olive oil) continued

• Rich in oleic acid (w-9)• Extra virgin=5mg phenols/10 g oil• 40g=4 tablespoons full• Increases HDL• LDL-c rich oleate more resistant to ox

LDL• Polyphenols = antiooxidants• Replacing dietary olive oil with

saturated fat significantly increases BP

Garlic, Heart disease 2000:2;3-9;phytochemistry

1992:31:2389-2391• Consisten dose dependant BP

reduction• Cultivated garlic = allium sativum

(not all garlic preparations are processed similarly and not comparable in antihypertensive effect)

• Wild uncultivated garlic = allium urisinum

Garlic mechanisms of action

• Garlic is a natural ace inhibitor and CCB• ACEi due to flvanolic compounds• Natural CCB / vasodilator (MG)• Increases NO• Decreases sensitivity to NE• Increases adenosine• Vasodilation• Inhibits AA metabolites (TxA2)• Reduces aortic stiffness (improves aortic

compliance)• Decreases ROS

Seaweed, J Nutr biochem 2000:11:430-4

• Wakame (undaria pinnatifida)• Most popular edible seaweed in Japan• Ace inhibition similar to captopril• Lowers SBP 14+-3 mmhg, DBP 5+-2mm

hg• Ion exchange sodium absorbing/potassium

releasing seaweed preparation• Mechanisms : ACEi, 771 minerals, fiber,

alginate colloid

Pyridoxine, vit b6 Mol cell Biochem 1998;188;137-148

• B6 increases cysteine synthesis from methionine• Cysteine is precursor of glutathione (antioxidant)• Cyteine nuralizes aldehydes and increases

excretion, as does glutathione• Decreases BP• Blocks calcium influx, improves insulin sensitivity• Reduces central sympathetic nervous system

activity• Decreases end organ responsiveness to

glucocorticoids, mineralocorticoids

LYCOPENE, paran study

• 30 subjects with HT, age 40-65• SBP fell 9mm hg (p<0.01)• DBP fell 7mm hg (p<0.01)• Improvement in lipid profile

Coenzyme q10, ubiquinone, Alternative Med Review 1996;

(1),(3):171-174• High correlation of coq10 deficiency

and hypertension• Coq10 reduces with age, disease,

oxidative stress,statins, CHD, HT, Hyperlipidaemia, DM, aerobic exercise, atherosclerosis, hyperthyroidism

• Dose 100-225mg/d…BP reduction occurs at 4-12 weeks after initiation

Coq10 continued

• Reduces total dose and frequency of administration of antihypertensive drugs

• Lowest serum pretreatment levels of coq10 have best reduction in BP

• Average BP reduction in all trials is 15/10mm hg

• Improves lipids, CHO metabolism, insulin sensitivity, decreases HR, decreases ROS, improves LV function, ischemia, angina, CHD, CHF, lowers NE levels

VITAMIN C

• SBP is reduced proportionately more than DBP, but both are decreased

• Epidemiological, observational, cross sectional and controlled studies confirm improvement of both SBP, DBP and HR

• Lipid profile seems to be beneficial with small reductions in TC, TG, and LDL and oxLDL, and a slight increase in HDL in women

• Dose 200-1000mg/d• Combinations with other antioxidants such as vit

e, beta carotene or selenium provide synergistic anti-hypertensive effects

N-Acetyl cysteine (NAC), J Am cell nutr 1986:5:137-151

• SHR study : normalizes BP by binding to excess aldehydes, reducing cytosolic ca and bp

• Thiol containing antioxidant, scavenges ROS• Supports glutathione synthesis intracellularly• Increases NO• Calcium channel blocker activity• Lowers homocysteine,lp(a) and platelet

aggregation• Improves ED in smokers (600mg)

L-arginine, J clin invest 1991:88:1559-67

• Reduces bp in humans with acute parenteral and chronic oral administration in normotensives, hypertensives, salt sensitive hypertensives, DM and hyperlipidemics

• In CHD it increases coronary artery bloodflow and decreases angina

• In peripheral arterial disease, blood flow is increased and claudication decreased

Taurine

• Clinical use : HT, hyperlipidaemia, arrhythmias, CHD, CHF

• Lowers BP, decreases proteinuria, decreases LVH, decreases SNS activity centrally

• Human study : fujita (19 hypertensive subjects, 6g taurine x 7 days, lowers BP 9/4.1mm hg(p<0.05)

• Mechanisms : diuresis, decreases homocysteine, increases insulin sensitivity, aldosterone

• Dose 2-3g

NATURAL COMPOUNDS AS ALTERNATIVES TO DRUGS…

DIURETICS• Hawthorne• Vit b6• Taurine• Celery• Gla• Vit c• Potassium, mg, ca• Protein• Fiber• Coq10• L-carnitine

NATURAL ALTERNATIVES TO B BLOCKERS AND CCA

• Hawthorne

• Central alpha agonists (CCA) reduces SNS activity

• Taurine, potassium, zinc, na restriction, protein, fiber, vit c, vit b6, co q10, celery, GLA, garlic

NATURAL DIRECT VASODILATORS

• Omega 3 FA• MUFA (omega 9)• K, Mg, Ca, soy, fiber• Flavoids• Vit c,e• Coq10• L-arginine• Taurine• Celery• ALA•

NATURAL CALCIUM CHANNEL BLOCKERS

• Alphalipoic acid• Vit c• Vit b6• Mg• NAC• Vit e• Celery, hawthorne• Omega 3, garlic• calcium

NATURAL ACE INHIBITORS

• Garlic• Seaweed• Tuna, sardines• Pycnogenol• Casein• Hydrolysed whey protein• Geletin• Omega 3• Egg yolks• Zinc• GLA

NATURAL ANGIOTENSIN RECEPTOR BLOCKERS

• Potassium• Fiber• Garlic• Vitamin c• Vitamin b6• Coq10• Celery• GLA

FAVOURITES

• ACEI : fishoil, whey protein, GLA• DIURETICS : taurine and b6• BETA BLOCKERS : hawthorne• VASODILATORS : omeg3,9, vit c also

coq10• CENTRAL ACTING : vit b6• CALCIUM CHANNEL BLOCKERS : lipoic

acid, mg, omega 3

Dr Craige GoldingPhone: 011 327 5212 011 463 0036 Fax: 011 327 4058

e-mail: craigeg@mweb.co.za

www.antiagingdoctor.co.za

Thank youThank you