In the first part of our special focus on heart health, NutraIngredients examines the science behind the potential health benefits of a new wave of ingredients, from blood pressure lowering peptides from dairy, to flavanols from cocoa.
Improved heart health relates to reducing the risk of developing cardiovascular disease (CVD), coronary heart disease (CHD), and stroke. Risk factors for these diseases are numerous, and include smoking habits, body weight, blood pressure, cholesterol levels, and physical exercise levels.
According to Frost and Sullivan, the heart health market in Europe is dominated by ingredients targeting cholesterol-reduction, with the big four listed as phytosterols, omega-3s, beta-glucan, and soy protein.
While these main players are looking at blood lipid and cholesterol levels, another area of interest for the industry is reduction of blood pressure in people with hypertension. And no wonder, with some one billion people worldwide reportedly suffering from high blood pressure.
High blood pressure (hypertension) is defined as having a systolic and diastolic blood pressure (BP) greater than 140 and 90 mmHg. It is a major risk factor for CVD.
An area of growing interest and investment is proteins derived from milk reported to offer blood pressure improvements. A meta-analysis published in Nutrition (Elsevier) in 2008 (Vol. 24, pp. 933–940) concluded that milk-derived isoleucine-proline-proline (IPP) and valine-proline-proline (VPP) may impact blood pressure in pre-hypertensive and hypertensive subjects.
Commercial interest in such products is also prevalent: DSM offers an ingredient called tensVida (formerly TensGuard), which is composed of the tripeptide isoleucine-proline-proline (IPP) derived from milk. A study published in the Nutrition Journal, found that a daily supplement of tensVida was associated with a reduction in systolic and diastolic blood pressure of 3.8 and 2.3 mmHg, respectively.
Such blood pressure reductions are similar to those achieved by lifestyle modifications, and such lifestyle changes have been calculated to reduce the risk of stroke by 15 percent, and coronary heart disease by 6 percent (Nutrition Journal, 2010, 9:52).
Puleva Biotech is also looking at the potential of hydrolyzed caseins from goat's milk to prevent the development of high blood pressure.
The mechanism of action of these ingredients is reported to relate to the angiotensin converting enzyme (ACE)-inhibitory activity of milk peptides. ACE inhibitors work by inhibiting the conversion of angiotensin I to the potent vasoconstrictor, angiotensin II, thereby improving blood flow and blood pressure.
Furthermore, Glanbia Nutritionals offers a proprietary peptide NOP-47 reported to improve blood vessel function (Nutrition Journal, 2009, 8:34). Researchers from the University of Connecticut reported that two weeks of supplementation with NOP-47 was associated with a 28 percent increase in artery dilation in health
The study’s lead researcher, Dr Jeff Volek, said: “This is the first time a natural peptide has been shown to positively impact vascular function using these techniques.”
With confectionery giants like Mars, Nestlé and Hershey putting considerable R&D spend into the topic, it is no wonder that the potential heart health benefits from flavanols from cocoa are generating interest.
A review of a decade’s worth of research into cocoa, published in the British Journal of Nutrition (2008, Vol. 99, pp. 1–11), stressed the importance of distinguishing between chocolate and cocoa. Cocoa refers to the non-fat component of cocoa liquor (finely ground cocoa beans), whereas chocolate refers to the combination of cocoa, cocoa butter, sugar, etc. into a solid food product..
According to Mars, the benefits of cocoa bean revolve around the flavanols (also known as flavan-3-ols or catechins), and particularly the monomeric flavanol (-)epicatechin.
Pooling much of the recent data up to 2007, a meta-analysis by researchers from the University Hospital of Cologne found that consumption of cocoa had significant positive effects on blood pressure.
Writing in the Archives of Internal Medicine (2007, Vol. 167, pp. 626-634), the Cologne-based scientists: “The magnitude of the hypotensive effects of cocoa is clinically noteworthy; it is in the range that is usually achieved with monotherapy of beta-blockers or antiotensin-converting enzyme inhibitors.”
Moreover, a study using Natraceutical’s CocoanOX powder, and funded by the company, found that rodents fed 300 milligrams of cocoa powder per kilogram of body weight experienced a reduction in blood pressure similar to a 50 mg/kg dose of Captopril, a well-known pharmaceutical anti-hypertensive (Journal of Agricultural and Food Chemistry, Vol. 57, pp. 6156-6162).
There has been much study, and controversy, regarding B vitamins and heart health. The hypothesis that B vitamins can reduce the risk of cardiovascular disease is based on their role in regulating homocysteine, an amino acid.
Previously, high levels of the amino acid, hyperhomocysteinemia, were said to be a marker for heart disease and thought to be a risk factor for atherosclerotic disease, which contributes to heart attacks.
The link was founded on the observation that children with homocystinuria – a rare genetic condition causing extreme elevations in homocysteine levels – have higher rates of cardiovascular disease. Such an observation was therefore generalized to the wider population, with the hypothesis indicating that supplementation with B vitamins may reduce blood homocysteine levels and reduce the risk of heart disease.
A number of high profile studies in people with established cardiovascular disease have not found any benefits of vitamin B supplementation. Indeed, results of a meta-analysis in the Archives of Internal Medicine (Vol. 170, pp. 1622-1631) of eight folic acid trials involving 37,485 participants found no benefits on the risk of major vascular events, cancer, or deaths, despite reducing homocysteine levels by 25 per cent.
The door is not shut on this topic however, with many people citing studies in sick populations do not answer the question as to whether long-term B vitamin supplementation, combined with other healthy lifestyle habits, could have helped prevent cardiovascular disease before it occurred at all.
Indeed, following the recent publication of more null results from a B vitamin-heart health study (JAMA, 2010, Vol. 303, pp. 2486-2494), Duffy MacKay, ND, vice president, scientific & regulatory affairs, for the dietary supplements trade association, the Council for Responsible Nutrition (CRN), said: “We may need to re-evaluate expectations when designing studies on nutrients used to treat serious chronic disease because it is unrealistic to expect a vitamin to undo a lifetime of unhealthy behaviors.”.
Moving from B to K, a growing body of evidence indicates that increased intakes of vitamin K may reduce the build up of calcium in arteries that leads to hardening of the blood vessels.
A study published in the journal Atherosclerosis, for example, found that higher intake of vitamin K2 (menaquinone), but not K1, was associated with a 20 per cent reduction in calcification of the arteries. Atherosclerosis, known as hardening or furring of the arteries is a key risk factor for cardiovascular disease, the cause of over 50 per cent of deaths in Europe and the US.
On the other hand, another study found that supplements of K1, also known as phylloquinone, may slow hardening of the arteries in people already suffering from the condition (American Journal of Clinical Nutrition, 2009, Vol. 89, pp. 1799-1807). The effects were said to be independent of changes in levels of a protein called matrix Gla protein (MGP). MGP is a regulator of calcium crystal formation in the circulatory system. MGP is a vitamin K-dependent protein - meaning vitamin K is required to activate this protein.
The Dutch authors of the Atherosclerosis study proposed that the differing pathways for metabolism of menaquinone and phylloquinone as the probable reason as to why the different forms of vitamin K showed different results with respect to calcification.
“Phylloquinone is predominantly transported with the triacylglycerol-rich fraction, which is mainly cleared by the liver. Phylloquinone is therefore very effectively cleared from circulation by the liver to function as a cofactor for proteins in blood coagulation,” wrote the researchers.
“Menaquinones, on the other hand, are found in both triacylglycerol-rich lipoprotein and low-density lipoprotein, which are equally transported to extrahepatic tissues,” they said. “Menaquinone could therefore more effectively influence MGP and coronary calcification.”
Antioxidants and berry extracts
Antioxidants, many of which are extracted from fruit and berries, have also been shown to exert vascular benefits. Results from a pan-European research team found that consumption of an antioxidant-rich raspberry juice or tea may prevent artery hardening.
Writing in the journal Food Chemistry (Vol. 118, pp. 266-271), researchers from the University of Montpellier 2, the University of Parma, and the University of Glasgow reported that consumption of raspberry, strawberry and bilberry juices and green and black tea reduced aortic deposits in hamsters fed a high fat diet.
The authors noted that, while all of the beverages exerted beneficial effects, the composition and concentration of individual phenolic compounds varied substantially between the five beverages. “This indicates that anti-atherosclerotic effects can be induced by a diversity of phenolic compounds rather than a few specific components,” they said.
Another European study, this time focusing exclusively on bilberry extracts, found that the antioxidant-rich extract may prevent the build up of plaques in the arteries of mice. The researchers stated that the active compounds in the fermented extract have yet to be identified, but suggested they may be anthocyanin-derived polymeric pigments (Journal of Agricultural and Food Chemistry, doi: 10.1021/jf9035468)
Amongst the minerals implicated in heart health via blood pressure lowering or improvements in vascular health are magnesium and selenium. A recent from Korea, for example, found that supplemental magnesium may reduce blood pressure in people with high blood pressure (Nutrition, Metabolism and Cardiovascular Diseases, doi: 10.1016/j.numecd.2009.01.002).
Participants received daily supplements of 300 mg of elemental magnesium in the magnesium oxide form or placebo for 12 weeks. The researchers report that significant decreases in both systolic and diastolic blood pressure were observed for hypertensive people receiving the magnesium supplements (17.1 and 3.4 mmHg, respectively), compared to placebo (6.7 and 0.8 mmHg, respectively)
Selenium has also been implicated in improved vascular health. The effects are proposed to be related to the body’s antioxidant defense system which includes enzymes, such as superoxide dismutase (SOD) and glutathione peroxidases (GPx's). A form of the latter, GPx-1, has been reported to modulate vascular function, according to in vivo animal data.
Findings of a study published in the American Heart Journal in 2008 (Vol. 156, pp. 1201.e1-1201.e11) showed that sodium selenite supplements for 12 weeks may increase levels of GPx-1.
“These data should spur further investigations to elucidate whether enhanced GPx-1 activity achieved by selenium supplementation has a protective role in cardiovascular disease during long-term follow-up,” concluded the researchers from Johannes Gutenberg-University in Mainz, Germany.
Vitamin E tocotrienols
One of the earliest reports to link tocotrienols to heart health – via cholesterol reduction – was a paper by Dr Asaf Qureshi at the USDA. Writing in the Journal of Biological Chemistry (Vol. 261, pp. 10544-10550.) in 1986, Dr Qureshi and his co-workers reported that the a cereal’s ability to reduce cholesterol concentrations was directly linked to its tocotrienol concentrations, with barley and oats coming out on top, followed by rye, wheat and then corn.
Another study of note followed in 1992 from researchers at Bristol-Meyers Squibb (again involving Dr Qureshi), which reported that gamma-tocotrienol was 30 times more active than the alpha-tocotrienol form at inhibiting cholesterol synthesis.
Human studies followed, with Dr Qureshi again leading the charge. In 1991 a pilot study (Am. J. Clin. Nutr ., Vol. 53, pp. 1021S-1026S) reported that supplementation with palm-derived tocotrienols was associated with a reduction in cholesterol levels in hypercholesterolemic subjects, with gamma-tocotrienol again identified as “the most potent cholesterol inhibitor in the [tocotrienol-enriched fraction of palm oil used in the study]”.
The presence of tocopherol in the mix is a source of debate, with a study from 1995 in Lipids (Vol. 30, pp. 1171-1177) reporting that alpha-tocopherol “attenuated the cholesterol-suppressive action of the tocotrienols”.
Indeed, a review by Mark Houston from Vanderbilt University School of Medicine last year explained: “Tocotrienol and tocopherol concentrates, often referred to as ‘tocotrienols-rich fractions’ (TRFs), are obtained from rice bran or palm oil and contain about 30 to 50 percent tocopherols.
“If the TRFs contain more than 20 percent tocopherols, the cholesterol-lowering effect is diminished.” (Prog Cardiovasc Dis, Vol. 52, pp. 61-94).
Tocotrienols from rice bran have also been linked to improved heart health, with a 2001 study, again from Dr Qureshi, reporting that rice bran-derived tocotrienols may inhibit atherosclerotic lesions mice (Journal of Nutrition, 2001, Vol. 131, pp. 2606-2618).
Carotech, the biggest player in the sector, lists the cardiovascular benefits associated with tocotrienols as improved arterial compliance, improved blood pressure, and increased antioxidant activity to improve ventricular function.
And recently, scientists from tocotrienol supplier Davos Life Sciences and Malaysia Palm Oil Board reported that palm-derived gamma and delta tocotrienols may lower triglyceride levels by 28 percent in the blood of human after two months of supplementation (Journal of Atherosclerosis and Thrombosis, Vol. 17, pp.1019-1032)
Our special edition on heart health will continue tomorrow with a focus on the main players in heart health: Plant sterols, omega-3s, beta-glucan, and soy protein.
Disclaimer: The list of ingredients presented in today’s article is not exhaustive and some ingredients may have been omitted.