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A worldwide research team assesses the evidence for nutrition-based solutions to the world’s number one killer
 Active prevention of coronary heart
disease (CHD) is usually started
immediately after its first clinical manifestation. Secondary prevention focuses on
risk reduction in people with established
CHD who are at high risk of recurrent cardiac events and death. It is important to remember that the
two main causes of death in these patients
are sudden cardiac death (SCD) and heart
failure, often resulting from myocardial
ischemia and subsequent necrosis.
Most investigators agree that atherosclerosis is a chronic low-grade inflammation
disease.1 Proinflammatory factors (free
radicals produced by cigarette smoking,
hyperhomocysteinaemia, diabetes, per
oxidised lipids, hypertension, elevated and
modified blood lipids) contribute to injure
the vascular endothelium, which results in
alterations of its anti-atherosclerotic and
antithrombotic properties. This is thought
to be a major step in the initiation and formation of arterial fibrostenotic lesions.1
Whatever the specific clinical aims of
the programme, nutritional evaluation
and counselling of each individual with
CHD must be a key point of the preventive
intervention. Nutrition is, however, only
one component of such a programme.
Exercise training, behavioural interventions (particularly to help the patient
abstain from smoking) and drug therapy have equally important roles.
We now examine whether diet
(and more precisely, certain dietary factors) may prevent (or help prevent) SCD
in patients with established CHD. We
focus our analyses on the effects of the different families of fatty acids, antioxidants
and alcohol.2
N-3 FATTY ACIDS AND SCD
The hypothesis that eating fish may
protect against SCD is derived from the
results of a secondary prevention trial,
the Diet and Reinfarction Trial, which
showed a significant reduction in total
and cardiovascular mortality in patients
who had at least two servings of fatty fish
per week.3 The authors suggested that the
protective effect of fish might be
explained by a preventive action on ventricular fibrillation, since no benefit was
observed on the incidence of nonfatal
acute myocardial infarction.
Nair and colleagues have also shown
that an important pool of free (non-esterified) fatty acids exists in the normal
myocardium and that the amount of n-3
PUFA in this pool is increased by supplementing the diet in n-3 PUFA.4 This illustrates the potential of diet to modify the
structure and biochemical composition of
cardiac cells. In the case of ischemia, phospholipases and lipases quickly release new
fatty acids from phospholipids, including
n-3 fatty acids in higher amounts than the
other fatty acids,4 thus further increasing
the pool of free n-3 fatty acids that can
exert an anti-arrhythmic effect.
A large prospective study (more than
20,000 participants with a follow-up of 11
years) examined the specific point that fish
has anti-arrhythmic properties and may
prevent SCD.5 Researchers found that the
risk of SCD was 50 per cent lower for men
who consumed fish at least once a week
than for those who had fish less than once
a month. Interestingly, the consumption of
fish was not related to nonsudden cardiac
death, suggesting that the main protective
effect of fish (or n-3 PUFA) is related to an
effect on arrhythmia.
An important point is that the protective effect of n-3 PUFA on SCD was greater
in groups of patients who complied more
strictly with the Mediterranean diet. This
suggests a positive interaction between n-3
PUFA and some components of the Mediterranean diet, which is, by definition, not high in n-6 PUFA and low in saturated fats, but rich in oleic acid, various
antioxidants and fibre, and associated with
a moderate consumption of alcohol.
ANTIOXIDANTS AND SCD
Vitamin E: The issue about the effect of
dietary antioxidants on the risk of CHD in
general and on SCD in particular is more
controversial. Regarding vitamin E, for
instance, the most widely studied dietary
antioxidant, there are discrepant findings
between the expected benefits based on
epidemiological observations and the
results of clinical trials.6,7
In a recent controlled trial, a significant
decrease in nonfatal acute myocardial
infarction and a nonsignificant increase in
cardiovascular mortality (in particular in
the rate of SCD) were reported with a daily
regimen of 400-800mg vitamin E in
patients with established CHD.8
Because of certain methodological
shortcomings, this trial was said to confuse rather than clarify the question of
the usefulness of vitamin E supplementation in CHD, and provided no indication
about possible links between vitamin E
and SCD prevention.
The GISSI-Prevenzione trial brings new
information in this regard. Unlike those of
n-3 PUFA, the results of vitamin E supplementation do not support a significant
effect on the primary endpoint, namely a
combination of death and nonfatal AMI
and stroke.9
However, the secondary analysis provides a clearer view of the clinical effect of
vitamin E in CHD patients, which cannot
be easily dismissed. In fact, among the 193
and 155 cardiac deaths that occurred in
the control and vitamin E group, respectively, there were 99 and 65 SCDs, which
indicated that the significant decrease in
cardiovascular mortality (by 20 per cent)
in the vitamin E group was almost entirely
due to a decrease in the incidence of SCD
(by 35 per cent). In contrast, nonfatal cardiac events and non-sudden cardiac
deaths were not influenced.9 These data
suggest that vitamin E may be useful for
the primary prevention of SCD in patients
with established CHD.
Despite the mixed results when the outcome measures are myocardial infarction
or stroke, there is considerable evidence
that vitamin E has a positive effect on
other measures of cardiovascular function.
For example, a double-blind, placebo-controlled, randomised study found that
1000IU vitamin E (all-racemic alpha-tocopherol) for three months improved
endothelial function and blood flow in
patients with type I diabetes and reduced
the oxidative susceptibility of LDL.10
Vitamin E therapy (eight weeks, chemical form not identified) was effective in
improving brachial artery reactivity.11
Brachial artery reactivity measures the change in brachial artery diameter after
release of an occluding cuff and is a measure of endothelial function. It is thought to
be a useful marker for atherosclerosis and
coronary artery disease.
Vitamin D: In addition to playing a
potential role in atherosclerosis, vitamin D
nutriture may also be an important factor
in the pathogenesis of congestive heart
failure.12,13 Congestive heart failure (CHF)
can have multiple aetiologies but is characterised by a reduced amount of blood
being pumped from the left ventricle of
the heart and, therefore, a reduced amount
of blood reaching other organ systems.
This disease is often the end stage of cardiac disease and, as more cardiac patients
survive their initial problems, the opportunity for developing CHF increases.
Observational studies have demonstrated an association of
vitamin D deficiency
in patients with
severe CHF.14 These
authors speculate
that low circulating
levels of vitamin D
metabolites could
contribute to the
aetiology of CHF.
Co-Q10: Compared with vitamin E, there has been only
very limited research on the potential cardiovascular benefits of co-Q10. Co-Q10
deficiency has been observed in a wide
variety of cardiovascular disorders — congestive heart failure, angina pectoris, coronary artery disease, cardiomyopathy,
hypertension, mitral value prolapse.15
In the apoE gene knockout mice (an
excellent model of human atherosclerosis)
supplementation with both vitamin E and
co-Q10 was found to inhibit atherosclerosis better than with vitamin E or co-Q10
alone.16 It is not known, however, if co-Q10
supplementation in humans can decrease
atherosclerosis.
Although co-Q10 may inhibit the formation of oxidised and atherogenic forms
of LDL, it is likely that the primary mechanism whereby co-Q10 could prevent
heart disease is through its ability to
improve ATP synthesis in cells with a high
ATP demand such as cardiac myocytes. As
an antioxidant, it could also inhibit the free
radical damage to the myocardium that
arises during ischemia-reperfusion injury.
It is logical to suggest that dietary co-Q10
supplementation could increase ATP production and thereby
improve myocardial
contractility.
A meta-analysis of
eight randomised controlled studies looking
at the effect of dietary
co-Q10 supplementation on congestive
heart failure indicates
an improvement in
stoke volume, ejection
fraction, cardiac output, cardiac index, and end diastolic volume index.17 These results certainly support a role for dietary co-Q10 supplementation as an adjunctive treatment for
congestive heart failure.
FUTURE TRENDS
The three lipid-soluble nutrients
reviewed above all have antioxidant properties and antioxidants are, in general,
anti-inflammatory. Dietary supplementation with vitamin E or vitamin D is associated with decreased levels of CRP, which is
a marker for inflammation and increased
risk of cardiovascular disease as well as in
type 2 diabetes.18,19
Surprisingly, there are no published
studies on the potential role of co-Q10
in reducing plasma CRP levels. In the
case of vitamin E, there should be
increased consideration for the non-alpha-tocopherol forms, particularly the
potential anti-inflammatory properties
of gamma-tocopherol.
| For co-Q10, the available data strongly
supports a role for supplementation for the treatment of congestive heart failure |
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For co-Q10, the available data strongly
supports a role for supplementation
(along with conventional therapy) for
the treatment of congestive heart failure.
Vitamin D is remarkably under-researched considering its very promising role as an anti-atherogenic factor.
Lifestyle modifications, ie, reasonable
exposure to sunlight, may be more
important than nutritional considerations in the case of vitamin D.
Moreover, as Steinberg and Witzum
suggested,20 the antioxidants might be
effective in inhibiting the initial stages of
human atherosclerosis and yet ineffective
or much less effective in reducing plaque
instability and rupture.
If this were the case, it might be necessary to find some way to assess early
stages of lesion development (eg, high-resolution ultrasound or magnetic resonance imaging) rather than relying on
the usual late clinical endpoints. Of
course, if the development of early
lesions were successfully inhibited, there
should eventually be a decrease in the
frequency of clinical events, but in that
case, the trials might need to extend
beyond the conventional five years.
FLAVONOIDS AND CARDIO HEALTH
Clinical observations, basic science and
several epidemiological studies have contributed to an emerging body of evidence for a potential role of flavonoids in the
prevention of cardiovascular disease
(CVD).21 Flavonoids have been shown to
inhibit the oxidation of plasma LDL,
decrease platelet function and modulate
cytokines and eicosanoids involved in
inflammatory responses.22,23 Several epidemiological studies suggest a protection
of a high flavonoid intake on the mortality of CHD.24,25,26,27
Some prospective studies on major
flavonoid sources, such as tea, have, however, shown large discrepancies in the relative
risk of death from CHD with relative risks
ranging from 0.42,28 0.62,27 1.0825 to 1.6.29
Also, a recent study on
the risk of CVD in
women failed to show a
protective effect of
flavonoid intake on the
risk of CVD.30
Although the picture
from epidemiological
studies on the relationship between risk of
CVD and intake of
flavonoids is inconsistent, the majority of
the studies suggest an inverse association
between intake of flavonoids and the risk
of CVD, which is supported by basic and
clinical studies on flavonoids. These indicate that flavonoids may have a protective
action that deserves further investigation
before final conclusions can be drawn.
The flavonoids constitute a large class of
polyphenols that are found ubiquitously
in the plant kingdom and are thus present
in fruits and vegetables regularly consumed by humans. They account for a
variety of colours in flowers, berries and
fruits, from yellow to red and dark purple.
INHIBITING INFLAMMATION
Several studies have investigated the
effect of flavonoids on platelet activation
and aggregation.31,32 Recent studies on the
flavonoids in cocoa have shown that epicatechin and its related oligomers, the procyanidins, also have potent anti-inflammatory properties.33
The low-molecular-weight procyanidins and epicatechin itself were shown to
be a potent inhibitor of human 5-lipoxygenase,34 and procyanidins from cocoa
were demonstrated to decrease platelet
function significantly in vivo in humans.23
Furthermore, another study showed
that the combination of quercetin and
catechin synergistically inhibited platelet
function in collagen-induced platelet
aggregation by antagonising the intracellular production of hydrogen peroxide.35
A recent study on flavonoids and the
platelet-activating factor and related
phospholipids in
endothelial cells during oxidative stress
showed that the
flavonoids hesperedin, naringenin
and quercetin were
able to mediate these
enzy-mes, and thereby limit the inflammatory response.36
Studies on anthocyanins have also
demonstrated that they are able to
inhibit platelet aggregation. Treatment
of humans with blueberry anthocyanins
for 60 days was found to reduce the ex
vivo platelet aggregation.37
This observation was supported in a
study finding after one week of treatment
a reduced platelet aggregation by red grape
juice, but not by orange or grapefruit
juice.38 Further indications of a beneficial
effect were observed by researchers who
found inhibitory effects on platelet aggregation in dogs and humans by red wine
and red grape juice, but not by white wine,
which could point to an anti-atherosclerotic effect of the anthocyanins.39,40
The flavonoids may furthermore mediate other anti-inflammatory mechanisms
involved in the development of cardiovascular disease. Studies indicate that they are
implicated in the modulation of the
monocyte adhesion in the inflammatory process of atherosclerosis.
The expression of intercellular adhesion molecule-1, playing a pivotal role in
the inflammatory response, was, for
example, shown to be mediated by
quercetin in human endothelial cells.41
Plasma metabolites of (+)-catechin and
quercetin modulated monocyte adhesion
to human aortic endothelial cells; these
researchers also found that the plasma
metabolites of catechin, but not of
quercetin, were potent inhibitors.42
This underlines the importance of investigating the biological effects of the metabolites present in vivo, eg the flavonoid
glucuronic and sulphate conjugates
instead of the parent compounds.
The endothelial function plays
an important role in regulating the
vascular function, and endothelial
dysfunction is associated with
increased CVD risk. Several animal and human studies have
shown that flavonoids also may
have favourable effects on the vascular endothelial function.43
EPIDEMIOLOGICAL EVIDENCE
Since the Zutphen Study in
1993,28 a number of epidemiological studies have been undertaken
on the association between
dietary flavonoid intake and the
risk of CVD. The majority of
studies revealed an inverse association
with the risk of CVD, although the outcomes of some of the studies are conflicting.
Overall, the protective effect of
flavonoids was strongest against the
mortality of CHD, whereas the effect on
risk of nonfatal incidences of CVD was
weaker or nonexisting.
The average daily flavonoid intake in
studies ranges from 2.6mg/day to 28.6mg/day, with quercetin as the dominating flavonoid in most of the studies.
However, the flavonoid intake in these
epidemiological studies was based mainly on the food composition tables generated by Hertog et al, covering only the
content of selected flavonols and flavones
in the food.44,45
 TEA AND WINE TIME
If intake data on additional flavonoids
had been included in these studies (eg the
citrus flavonoids, the catechins, the anthocyanins and the isoflavonoids), the
flavonol quercetin would probably not
have been the major dietary flavonoid in
the cohorts. Further, tea would perhaps be
a less important flavonoid source, and the
outcome of studies would then possibly
have been different. The quercetin intake
originated mainly from tea intake, but
apples and onions were also important
sources of quercetin in some studies25,28
Early studies showed a highly protective
effect of both quercetin and tea against
CVD.28,46 However, some of the later and
larger cohort studies, trying to confirm
these early studies, found no association or
even aggravating effects of flavonoids and
especially of tea consumption.25,29,30,47
The association of tea and incidences of
CVD were later further investigated in several cohort studies. These studies have all
been reviewed in a recent meta-analysis on
the relationship between tea consumption
and stroke, myocardial infarction and all
CHD in 10 cohort studies and seven case-control studies.48
| Anthocyanins are present in red wine, and
studies suggest that wine drinkers have a lower mortality from CVD than others |
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The incidence rate of myocardial infarction was concluded to be weakly inversely
associated (11 per cent) with an increase in
tea consumption of three cups per day.
However, the authors, stressing that the
heterogeneity of the studies and the risk of
bias due to the larger number of smaller
studies show a protective effect, urge caution in interpreting this result.
The mechanism of the protective effect
of tea has recently been investigated and
does, however, support a beneficial effect
of tea intake. For example, consumption
of 900 ml black tea for four weeks
reversed the endothelial vasomotor dysfunction in patients with proven coronary artery disease.49
It has been suggested that the catechin
content in tea could be the protective factor, and researchers in 2001 thus estimated the catechin intake to 72 +/-47.8mg/day in the Zutphen Elderly Study
and found a significant negative association between ischemic heart disease and
intake of tea catechins.50
However, in another study on catechin
intake by the same authors, in post-menopausal women from Iowa, a protective effect of catechins was seen from only
dietary sources other than tea.51
The intake of red wine has been postulated to explain the French paradox — the
low incidence of CHD in France despite
the main risk factors for this disease
being similar to those in northern
European countries.52
Anthocyanins are present in red wine,
and several cohort studies have in fact suggested that wine drinkers have a lower
mortality from CVD than others.53,54,55
Other cohort studies have, however, found equally beneficial effects of all alcoholic beverages, and there is no general
agreement on this matter.56
It has been proposed that the possible
lower mortality by CVD in wine drinkers
could be due in part to differences in
lifestyle – that is, in dietary habits and
exercise, since factors such as dietary fat
composition, little exercise and hypertension are major risk factors on the development of atherosclerosis.57
FLAVONOID MECHANISMS
The overall picture of the flavonoids as a
protective agent against cardiovascular
disease has been consolidated during the
past decade. The mechanism of action of
the flavonoids is, however, still unknown,
but recent studies have moved the focus
away from the antioxidant properties of
the compounds toward a broader view on
the potential mechanisms of action
including especially the anti-inflammatory
effects of flavonoids.
The early research on the dietary protective action of flavonoids has mainly
focused on the flavonols, especially on
quercetin, in part because of limitations in
the available analytical methods at that
time, which merely restricted the investigations to this class of compounds.
However, within the past few years,
flavonoid research has produced evidence
for the importance of other dietary
flavonoid classes and subgroups with
potential health protective properties and
with a similar or even greater impact on
our total daily flavonoid intake. Examples
are the citrus flavonoids, the red-coloured
anthocyanins, the tea catechins, and the
procyanidins present in cocoa and wine.
Furthermore, there are indications of
the importance of a diet rich in a range of
different flavonoids, rather than containing a high concentration of an individual
compound, since some studies have
shown additive or even synergistically
effects of flavonoids.58
Authors: N-3 fatty acids:
M de Lorgeril and P Salen,
Universite Joseph Fourier de
Grenoble, France.
Fat-soluble antioxidants: W L
Stone and G Krishnaswamy,
East Tennessee State
University, US, and H Yang,
Yunnan College of Traditional
Chinese Medicine, China.
Flavonoids: S E Rasmussen,
Danish Institute for Food and
Veterinary Research,
Denmark.
Excerpted from Functional
Foods, Cardiovascular
Disease and Diabetes, A
Arnoldi, editor. ISBN 1 85573
735 3. Published by Woodhead
Publishing Ltd, England.
www.woodheadpublishing.com
Respond: editor@ffnmag.com
VITAMIN E AND C-REACTIVE PROTEIN
C-reactive protein (CRP) is emerging as a
major risk factor for atherosclerosis
and cardiovascular disease.1 The association between atherosclerosis and CRP is
strong even in the absence of classical risk
factors such as high cholesterol, triglycerides and blood pressure.2
A number of studies have now shown
that vitamin E supplementation reduces
levels of CRP. In a double-blind, placebo-controlled, randomised study of 57 people
with type 2 diabetes, subjects received
placebo for four weeks and were then randomised to receive tomato juice
(500ml/day), vitamin E (800IU/day, chemical form not specified), vitamin C
(500mg/day), or continued placebo treatment for four weeks.
Vitamin E supplementation was found to
decrease CRP levels.3
Since vitamin E has been shown to
reduce levels of CRP, it is reasonable to suggest that vitamin E supplementation could,
thereby, reduce the risk of future CVD. This
suggestion rests on the assumption that
CRP is a causative factor and not just a
marker for CVD. The evidence supporting
this assumption is not yet conclusive but is
certainly intriguing.
New research has shown that CRP
directly causes the induction of adhesion
molecules on the endothelial cells of both
human veins and arteries.4 The expression
of these adhesion molecules is known to
be essential for the development of CVD.
—WS, GK, HY
References
1. Folsom AR. Exp Gerontol 1999; 34:483-90.
2. Ridker PM, et al. New Engl J Med 2001; 344:1959-65.
3. Upritchard JE, et al. Diabetes Care 2000; 23:733-8.
4. Pasceri V, et al. Circulation 2000; 102:2165-8.
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DEFICIENCY IN SPECIFIC MICRONUTRIENTS
The human data offers the following
conclusions of note to formulators:
Calcium: Cases of hypocalcaemia-induced cardiomyopathy (usually in
children with a congenital cause for
hypocalcaemia) that can respond dramatically to calcium supplementation
have been reported.1
Magnesium: Hypomagnesaemia is
often associated with a poor prognosis in
congestive heart failure (CHF), and correction of the magnesium levels (in
anorexia nervosa, for instance) leads to
an improvement in cardiac function.2
Zinc: Low serum and high urinary zinc
levels are found in CHF,3 possibly as a
result of diuretic use, but there is no data
regarding the clinical effect of zinc supplementation in that context. In a recent
study, plasma copper was slightly higher
and zinc slightly lower in CHF subjects
than in healthy controls.4
It is not possible to say whether these
copper and zinc abnormalities may contribute to the development of CHF or are
simply markers for the chronic inflammation known to be associated with CHF.5,6
Further studies are needed to address the
point, since the implications for prevention are substantial.
Selenium: Selenium deficiency has
been identified as a major factor in the
aetiology of certain nonischaemic CHF
syndromes, especially in low-selenium
soil areas such as eastern China and
Western Africa.7 Selenium deficiency is
also a risk factor for peripartum cardiomyopathy.
Vitamin B1: Low whole blood thiamine (vitamin B1) levels have been documented in patients with CHF on loop
diuretics and hospitalised elderly
patients, and thiamine supplementation
induced a significant improvement in
cardiac function and symptoms.8
—ML, PS
References
1. Rimailho A, et al. Improvement of hypocalcemic cardiomyopathy by correction of serum calcium level. Am Heart J 1985; 109:611-3.
2. Gottlieb SS, et al. Prognostic importance of the serum magnesium concentration in patients with congestive heart failure. J Am Coll Cardiol 1990; 16:827-31.
3. Golik A, et al. Type II diabetes mellitus, congestive cardiac failure and zinc metabolism. Biol Trace Elem Res 1993; 39:171-5.
4. de Lorgeril M, et al. Dietary blood antioxidants in patients with chronic heart failure. Insights into the potential importance of selenium in heart failure. Eur J Heart Failure 2001; 3:661-9.
5. Levine B, et al. Elevated circulating levels of tumor necrosis factor in severe chronic heart failure. N Engl J Med 1990; 323:236-41.
6. Anker SD, et al. Tumor necrosis factor and steroid metabolism in chronic heart failure: possible relation to muscle wasting. J Am Coll Cardiol 1997; 30:997-1001.
7. Ge K, Yang G.The epidemiology of selenium deficiency in the etiological study of
endemic diseases in China.Am J Clin Nutr (Suppl) 1993; 57:259S-263S.
8. Shimon I, et al. Improved left ventricular function after thiamine supplementation in patients with congestive heart failure receiving long-term furosemide therapy. Am J Med 1995; 98:485-90.
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CAN DIET DO IT?
The vital importance of micronutrients for health and the fact that
several micronutrients have antioxidant properties are now fully recognised. These may be as direct antioxidants, such as vitamins C and E, or as
components of antioxidant enzymes:
super oxide dismutase or glutathione
peroxidase.1
It is now widely believed (but still
not causally demonstrated) that diet-derived antioxidants may play a role
in the development (and thus in the
prevention) of CHF. For instance, clinical and experimental studies have
suggested that CHF may be associated with increased free radical formation2 and reduced antioxidant
defences5,8 and that vitamin C may
improve endothelial function in
patients with CHF.3
In the secondary prevention of CHD, in dietary trials in which the tested diet included high intakes of natural antioxidants, the incidence of new episodes of CHF was reduced in the experimental groups.4,5 Taken altogether, these data suggest (but do not demonstrate) that antioxidant nutrients may help prevent CHF in post-infarction patients.
Thus, any dietary pattern combining a high intake of natural antioxidants, a low intake of saturated fatty acids, a high intake of oleic acid, a low intake of omega-6 fatty acids and a high intake of omega-3 fatty acids would logically produce a highly cardio protective effect. This is consistent with what we know about the Mediterranean diet pattern,6,7 and with the results of the Lyon Diet Heart Study,5,8,9 and what was recently confirmed by epidemiological studies.10,11
—ML, PS
References
1. Evans P, Halliwell B. Micronutrients: oxidant/antioxidant status. Br J Nutr 2001; 85:S67-S74.
2. Dhalla AK, et al. Role of oxidative stress in transition of hypertrophyto heart failure. J Am Coll Cardiol 1996; 28:506-14.
3. Hornig B, et al. Vitamin C improves endothelial function of conduit arteries in patients with chronic heart failure. Circulation 1998; 97:363-8.
4. Singh RB, et al. Randomised controlled trial of cardioprotective diet in patients with recent acute myocardial infarction : results of one year follow-up. BMJ 1992; 304:1015-9.
5. de Lorgeril M, et al. Mediterranean diet, traditional risk factors and the rate of cardiovascular complications after myocardial infarction. Final report of the Lyon Diet Heart Study. Circulation 1999; 99:779-85.
6. de Lorgeril M, Salen P. Modified Mediterranean diet in the prevention of coronary heart disease and cancer.World Rev Nutr Diet 2000; 87:1-23.
7. Simopoulos AP, Sidossis LS. What is so special about the traditional diet of Greece. The scientific evidence.World Rev Nutr Diet 2000; 87:24-42.
8. de Lorgeril M, et al. Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease. Lancet 1994; 343:1454-9.
9. Kris-Etherton P, et al. Lyon Diet Heart Study. Benefits of a Mediterranean-style, National Cholesterol Education Program American Heart Association Step I Dietary pattern on cardiovascular disease. Circulation 2001; 103:1823-5.
10. Marchioli R, et al. Mediterranean dietary habits and risk of death after myocardial infarction. Circulation 2000; 102(Suppl II):379.
11. Trichopoulou A, et al. Adherence to a Mediterranean diet and survival in a Greek population. N Engl J Med 2003; 348:2599-608.
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COMBINATIONS SPUR ON HEART-HEALTH MARKET
The meeting of science-backed proprietary ingredients and the condition-specific market
is driving innovation today.
With a suite of heart-health ingredients that includes vitamin E, coenzyme Q10, sterols
and its proprietary Sytrinol, it naturally was not long before SourceOne Global Partners
came upon the idea to start offering combinations to manufacturers.
The first manifestation will be evidenced in the first quarter of 2006 when the Chicago-based company rolls out Cholesstrinol — a combination of Sytrinol and plant sterols that go
at cholesterol reduction from different yet complementary means. "Certainly Sytrinol is our
key product," says Jim Roza, vice president of business development, technology and science at SourceOne. "We work with companies to put together Sytrinol with policosanol or
Sytrinol with co-Q10."
Nordic Naturals is also on the bandwagon, manufacturing Heart Synergy, which includes
fish oils EPA and DHA with co-Q10, L-carnitine, magnesium, vitamin E, selenium and folic
acid. "Co-Q10 and L-carnitine work better together for heart support," says Gretchrn
Vannice, research coordinator for the company. "This formula offers a complete nutritional solution."
Sigma-tau HealthScience took its carnitine know-how and partnered with Valen Labs for
their D-ribose, and Tishcon for their liposomal LiQsorb co-Q10. Mixing them together, they
added a dash of resveratrol, and is now marketing ResveraCarn, a ready-to-drink nutraceutical beverage in its LivingTonics line.
Partnering with other branded ingredients has its advantages. "In order to be vertically
integrated from a GMP standpoint, you have to understand the pedigree of your raw materials," says Ken Hassen, PhD, Sigma-tau’s chief operating officer. "We’re showing the customer that you get the trademark and identity of our products, but also you can see further back to see you’re getting marks from other trusted suppliers."
—Todd Runestad
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REFERENCES
1. Ross R. Atherosclerosis: an inflammatory disease. N Engl J Med 1999; 340: 115-26.
2. de Lorgeril M, et al. Dietary prevention of sudden cardiac death. Eur Heart J 2002; 23:277-85.
3 Burr ML, et al. Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: Diet And Reinfarction Trial (DART). Lancet 1989; 2:757-61.
4. Nair SD, et al. Cardiac (n-3) non-esterified fatty acids are selectively increased in
fish oil-fed pigs following myocardial ischemia. J Nutr 1999; 129:1518-23.
5. Albert CM, et al. Fish consumption and the risk of sudden cardiac death. JAMA
1998; 279:23-8.
6. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study Group. The effect
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