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Supplements For

Cardiac
Protection
By CJ Lau
15 July 2009
What are dietary
supplements?
 a product (other than tobacco) that is
intended to supplement the diet which
contains one or more of the following dietary
ingredients: a vitamin, a mineral, a herb or
other botanical, an amino acid, a dietary
substance for use by man to supplement the
diet. It is intended for ingestion in pill,
capsule, tablet or liquid form, and should not
be used to replace a meal or diet.
 In UK, the definition includes substances
such as garlic, ginseng, psyllium, enzymes,
fish oil and other ingredients.
Cardiac Protection
Supplements
Outline
 Coenzyme Q10

 Fish Oil

 L- Carnitine

 Antioxidant

 Folic acid
Coenzyme Q10
(Ubiquinone)
 Is a naturally occurring enzyme cofactor found in the
mitochondria of the body cells.
 It is involved in electron transport and supports the
synthesis of adenosine triphosphate (ATP) in the
mitochondrial membrane
 It is a fat-soluble antioxidant that helps to stabilise cell
membranes, preserving cellular integrity and function
 It may be obtained from the diet or a food supplement,
but it is also produced endogenously
Coenzyme Q10
 Meat and fatty fish products are the most
concentrated sources
 smaller quantities are found in wholegrain
cereals, soya beans, nuts and vegetables,
particularly spinach and broccoli
 no Dietary Reference Values or RDAs
have been established as it is not an
essential nutrient
 Deficiency has been linked to chronic
heart failure, ischemic heart disease,
cardiomyopathy and hypertension
Coenzyme Q10
 Coenzyme Q10 is sold in capsules and tablets in
strengths of 10–150 mg.
 Doses used in studies investigating CVD have ranged
from 100 to 150 mg daily. Higher doses have been
used in angina (150–600 mg daily).
 Safety in pregnancy has not been established.
 Coenzyme Q10 seems to be safe and relatively well
tolerated in doses of up to 10–200 mg daily. There are
occasional reports of gastrointestinal discomfort,
dizziness and skin rash, but these tend to occur with
doses > 200 mg daily.
Drug Interaction

 Simvastatin, pravastatin and lovastatin reduce


endogenous synthesis of coenzyme Q10
 Case reports suggest that coenzyme Q10 may
decrease international normalised ratio (INR) in
patients previously stabilized on anticoagulant.
In patients on warfarin, high doses of coenzyme
Q10 should be used with caution.
Clinical efficacy
 Coenzyme Q10 inhibits superoxide dismutase and
may have a role in antioxidant.
 A meta-analysis of eight clinical trials (1997) of
coenzyme Q10 in patients with CHF found that
supplemental treatment of CHF was significant,
with significant improvement in stroke volume,
ejection fraction, cardiac output, cardiac index and
diastolic volume index.
 However, not all clinical trials show positive
results. A recent randomized ,double blind studies
of patients with New York Heart Association class
III and IV heart failure did not show significant
improvement in ejection fraction after receiving
200mg coenzyme Q10.
Clinical efficacy
 In another RCT, 55 patients with CHF were randomly
assigned to receive 200 mg coenzyme Q10 or a placebo
daily for 6 months. Patients receiving the supplement
had higher serum concentrations of coenzyme Q10, but
there were no differences in cardiac performance, peak
oxygen consumption and exercise duration between the
treated group and the placebo group.
 As for angina, in one RCT, 144 patients with acute
myocardial infarction were given 120 mg coenzyme Q10
or a placebo daily for 28 days, starting within 3 days of
the heart attack. There was a significant improvement in
angina pectoris, total arrhythmias and poor left
ventricular function in the intervention. However, further
studies are needed to support these findings.
Clinical efficacy
 Studies in hypertension are
inconclusive although there are two
studies suggesting a reduction in
systolic and diastolic blood pressure
with coenzyme treatment.
Overall
 Results from preliminary studies with
coenzyme Q10 suggest that it may help
improve symptoms of CHF, and may help to
protect against myocardial infarction
 At present, coenzyme Q10 lacks definitive
data for recommendation in patients with
coronary artery disease or heart failure.
 Prospective examination is certainly needed
with possibly longer duration of therapy
before any conclusion is possible.
 All patients with cardiovascular conditions
should take medical advice before taking
coenzyme Q10.
Fish Oil
 Fish liver oil is generally derived from the liver of
the cod or shark
 Fish body oil usually derived from sardine or
anchovy
 Fish liver oil is a rich source of vitamins A and D as
compared to fish body oil.
 Both fish liver oil and fish body oil are sources of
polyunsaturated fatty acids (PUFAs) of the omega-3
series [eicosapentaenoic acid (EPA) and
docosahexaenoic acid (DHA)].
 WHO suggests 2 portions of fish intake/week, which
is equivalent to 250-500mg/daily EPA + DHA.
Fish Oil
 Fish oil are thought to have several effects:
1. reduces plasma triglycerides level
2. Inhibition of atherosclerosis
3. Prevention of thrombosis
 Fish oil appears to act by
1. modulation of pro-inflammatory and pro-
thrombotic eicosanoid (prostaglandin,
thromboxane and leukotriene) production
2. reduction in interleukin-1 and other cytokines
Fish Oil
 US systemic review (2004) found that the strongest and
most consistent effect of omega-3 fatty acids is on
lowering triglycerides. In general, LDL cholesterol and
HDL cholesterol were found to rise to a small extent.
 A meta-analysis (2002) of 11 RCTs that compared
dietary or non-dietary intake of n-3 fatty acids with
placebo in patients with CHD found that intake of n-3
fatty acids reduces mortality due to myocardial
infarction and sudden death in patients with CHD.
 A large Japanese trial (2007) in 18 645 patients with a
total cholesterol of 6.5 mmol/l or greater, randomised
patients to receive either EPA 1.8 g daily with a statin
or a statin control with a 5-year follow-up. There was a
19% relative reduction in major coronary events in the
EPA group compared to the statin control group. The
benefits were in addition to statin treatment.
Fish Oil
 Dose – not established, but doses of 1-2g/daily
(combined EPA/DHA) may be adequate
 Use in pregnancy should be supervised because of
the potential for vitamin A toxicity with excessive
intake of fish oil
 Adverse effects - safety concern includes the
potential to increase bleeding time. Intake of
<3g/daily of EPA/DHA should not be a problem.
Patients taking anticoagulant medications should
inform their doctors if they are taking fish oil.
Interactions – anticoagulants, gingko biloba and
ginseng. May increase the risk of bleeding, use of
fish oil should be medically supervised.
L-Carnitine
 Carnitine is an amino acid derivative, L-carnitine is the
naturally occurring carnitine
 Carnitine may be beneficial in patients with ischaemic
heart disease, but only those who have low serum
carnitine levels
 Orally administered L-carnitine (2 g daily) has been
shown to improve symptoms of angina, and to reduce
anginal attacks and glyceryl trinitrate consumption
(1980).
 Carnitine supplementation (4 g daily) has also been
reported to improve heart rate, arterial pressures,
angina and lipid patterns in a controlled study of
patients who had experienced a recent myocardial
infarction (1992).
Overall
 Preliminary studies (1979) have shown that l-carnitine may
reduce blood cholesterol levels. Oral administration of l-
carnitine (3–4 g daily) significantly reduced serum levels of
total cholesterol or triglyceride or both, and increased those
of high-density lipoprotein (HDL) cholesterol.
 No sufficient evidence to guarantee the safety of carnitine in
pregnancy use
 Dose- not established, but doses of 1-6g have been used in
studies
 Nausea, vomiting and diarrhea may occur in high doses
 Anticonvulsants, pivampicillin may increase excretion of
carnitine
Antioxidants
 Antioxidants offer protection against free radicals and
prevent damage to vital biological structures such as
lipid membranes, proteins and DNA.
 vitamin A (usually as beta-carotene), vitamins C and E
are marketed as supplements having antioxidant
activity.
 beta-carotene are found in most dark green, red or
yellow fruits and vegetables.
 Epidemiological evidence suggests that low plasma
levels of antioxidant nutrients and low dietary intakes
are related to an increased risk of coronary heart disease
(CHD).
Clinical efficacy
 One systematic review assessed whether antioxidants in
food or supplements can offer primary prevention against
myocardial infarction or stroke. Eight RCTs were included,
six of which tested supplements of beta-carotene and two
on ascorbic acid. None of the RCTs showed any benefit of
antioxidant supplementation on CVD.
 A large trial (2002) involving 20 536 UK adults aged 40–80
with coronary disease, other occlusive arterial disease or
diabetes, randomly allocated participants to receive
antioxidant vitamin supplementation (600 mg vitamin E,
250 mg vitamin C and 20 mg beta-carotene daily) or
matching placebo over 5 years. There were no significant
differences in all-cause mortality, or in deaths due to
vascular or non-vascular causes.
 In 2004, the American Heart Association Council on
Nutrition, Physical Activity and Metabolism concluded that
antioxidant supplements have little or no proven value for
preventing or treating CVD.
Folic Acid
 Folic acid is a water-soluble vitamin
 Marginal folate status is also associated with
elevated plasma homocysteine levels, a known
risk factor for CVD mortality.
 Current studies support a link between
homocysteine and atherosclerosis. However,
there has not been a definite link between
reduction of homocysteine level ands and
prevention or resolution of coronary artery
disease.
 Dose- as a dietary supplement, oral, 100–
500 μg daily
Role of Pharmacists
 able to assess an individual’s risk of nutrient
deficiency and need for further referral
 must not give the impression that any dietary
supplement is efficacious when there is no
evidence for such efficacy
 There is a need to be aware of the potential for
adverse effects with supplements and drugs
interactions
 Help patient in making informed decision
References
 Goodnight SH Jr, Harris WS, Connor WE, Illingworth DR.
Polyunsaturated fatty acids, hyperlipidaemia and thrombosis.
Arteriosclerosis 1982; 2: 87–113.
 Bucher HC, Hengstler P, Schindler C, et al. N-3 polyunsaturated
fatty acids in coronary heart disease: a meta-analysis of
randomized controlled trials. Am J Med 2002; 112: 298–304
 Yokoyama M, Origasa H, Matsuzaki M, et al. Effects of
eicosapentaenoic acid on major coronary events in
hypercholesterolaemic patients (JELIS): a randomised open-
label, blinded endpoint analysis. Lancet 2007 369: 1090–1098
 Food and Drug Administration Final Rule. Substances affirmed
as generally recognized as safe: menhaden oil. Fed Reg 1997;
62: 30750–30757
 Kamikawa T, Suzuki Y, Kobayashi A, et al. Effects of l-carnitine
on exercise tolerance in patients with stable angina pectoris.
Jpn Heart J 1984; 25: 587–597
References
 Davini P, Bigalli A, Lamanna F, et al. Controlled study on l-carnitine
therapeutic efficacy in post-infarction. Drugs Exp Clin Res 1992
 Kris-Etherton PM, Lichtenstein AH, Howard BV, et al. Antioxidant
vitamin supplements and cardiovascular disease. Circulation 2004;
110: 637–641.
 Heart Protection Study Collaborative Group. MRC/BHF Heart
Protection Study of antioxidant vitamin supplementation in 20,536
high-risk individuals: a randomised placebo-controlled trial. Lancet
2002; 360: 23–33.
 Gaytan RJ, Michael PL. Oral nutritional supplements and heart
disease: a review. American Journal of Therapeutics 8, 255-274.
 Wald DS, Wald NJ, Morris JK, Law M. Folic acid, homocysteine, and
cardiovascular disease: judging causality in the face of inconclusive
trial evidence. BMJ 2006; 333: 1114–1117
 Dietary supplements database, medicines complete.

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