The cardiovascular system is the body's red river, a veritable waterway of blood that is ferried by arteries and veins from its pumping station, the heart, throughout the body, delivering oxygen and nutrients to cells and transporting waste away. We are interested in maintaining a healthy cardiovascular system not least because it is the top reason we die — more than one of every three of us die from heart disease.
As they say, crisis equals opportunity, and the cardio-health market is ripe for the nutrition market providing solutions to help maintain and regulate a healthy system — keeping triglycerides, blood pressure and cholesterol levels in check as well as improving arterial health.
Nutrients can help address all of these symptoms. Whether you are thinking of launching a new product in this area — or refurbishing an old one by adding that 'new and improved' ingredient — there is much science to validate the nutritional approach. This fact has not been lost on marketers — 134 new food and beverage products targeting cardiovascular health were launched in the United States between January 1 and September 23 of 2008, according to Mintel's Global New Products Database.
The easy target is cholesterol levels, in particular keeping LDL cholesterol levels low (keeping HDL levels high is another good target, though more elusive to remedy). Doctors routinely counsel patients to keep cholesterol levels below 200mg/dL.
The inconvenient truth is that about an equal number of people die from cardio events with cholesterol below 200 as above. A Harvard physician, in a 2007 Lancet paper titled 'Are Lipid-Lowering Guidelines Evidence-Based?' described how no studies have shown statin cholesterol-lowering drugs to be effective for women at any age, nor for men 69 years of age or older, who do not already have heart disease or diabetes.1 Indeed, studies show between 45 and 60 per cent of patients hospitalised for a heart attack have a 'normal level' of cholesterol.2,3
So, if cholesterol won't necessarily give you a heart attack, what will? A 2007 study at the Cooper Clinic in Texas suggests the answer may be calcium. After controlling for age, gender, blood lipids, diabetes, tobacco use, hypertension and family history of premature heart disease among 303 patients, those with a coronary artery calcium score of less than 10 had only 1.7 per cent likelihood of having ischemia, or decreased arterial blood flow. For those with higher levels of calcium, the likelihood was 20 per cent — a greater than ten-fold difference.4
Some studies show that coronary calcium content is a good predictor of future coronary events in both symptomatic and asymptomatic populations.5,6,7 These studies indicate that abundant mature coronary plaque is at least a risk factor for clinical events and, possibly, is a cause of those events. But other studies show that some patients with acute coronary syndromes have little or no coronary calcium.8,9,10
So, controversy remains about whether calcium in plaque is a marker of stability or instability. When plaque is unstable, it is thought to lead to heart attack and stroke, respectively.
If calcium-rich plaque deposits are indeed the harbinger of doom, one answer is surely vitamin K2, in particular the long-chain menaquinones. Only relatively recently has vitamin K2's role been delineated as being able to activate proteins responsible for calcium utilisation in bones. And just in the last few years has it been discovered that K2 activates matrix GLA protein, a prime inhibitor of vascular calcification. The upshot is a blockbuster nutrient that removes calcium from arteries, where it is not needed, and places calcium in bones, where it is.
Groups with the highest amounts of vitamin K from dietary sources such as spinach and broccoli exhibit more than a 50 per cent reduction in coronary heart disease mortality and aortic calcium scores.11
In a recent animal study, K2 supplementation reduced accumulated arterial calcium deposits, which was accompanied by enhanced arterial elasticity.12 (For its part and not to be overlooked as another wonder nutrient, vitamin D has also been shown to be correlated with the absence of extensive arterial calcification.13)
In human models, 45mcg/day vitamin K2 is seen as an efficacious dose. Once available only as a supplemental ingredient, K2 became available for the food market earlier this year.
Omega-3s fish oils
If you just can't live without a little calcium in your arteries, fish oils have the benefit of easing the stickiness of blood platelets.14 This makes the blood slide more smoothly past plaque deposits so that a chunk of plaque is less likely to break off and cause a sudden-death heart attack. A recent meta-analysis of omega-3 trials shows fish oils reduce coronary heart disease mortality by 36 per cent and total deaths by 17 per cent.15
When it comes to heart health, fish oils target a vast array of aspects. Epidemiologic and clinical trials have shown that omega-3 fatty acids reduce cardiovascular disease incidence.16,17 Large-scale epidemiologic studies suggest that people at risk for coronary heart disease benefit from consuming omega-3 fatty acids from plants and marine sources.18 They can also prevent arteriosclerosis by inhibiting the development of plaque and blood clots that can clog arteries.19 They can decrease risk of arrhythmias, which can lead to sudden cardiac death; decrease triglyceride levels; decrease growth rate of atherosclerotic plaque;20,21,22 and reduce blood pressure in individuals with hypertension.23 They're one of the few nutrients that can raise HDL cholesterol. Some studies show they can also raise LDL cholesterol, but the relative trade-off with HDL-raising means an overall net cholesterol benefit.24
The ideal amount to take isn't clear. There is as yet no official recommended daily intake amount, though industry groups are pushing for that. The success of any effort could displease non-EPA/DHA forms of omega-3s, which would presumably be left out in the cold because the FDA's qualified health claim is exclusively for EPA/DHA — other omega-3 forms skate into the market using nutrient content claims for 'omega-3s' in general. Evidence from prospective secondary prevention studies suggests that taking EPA plus DHA ranging from 0.5 to 1.8g/day significantly reduces deaths from heart disease and all causes.25 For alpha-linolenic acid (from flax and other sources), a total intake of 1.5 to 3g/day seems beneficial.26 Even the staid American Heart Association (AHA) recommends healthy people consume about 1g/day EPA plus DHA. For those who need to lower triglycerides, the AHA recommends 2 to 4g/day EPA plus DHA.
The beauty of omega-3s (in particular EPA and DHA) from a marketer's perspective is that, while according to the FDA their benefit as of now is only related to heart health, the research is amassing demonstrating benefit for just about everything from ADHD to diabetes.27,28 Truly, fish oils are the Swiss Army Knife ingredient.
The power of allopathic medical doctors in Western societies telling patients that heart disease is all about keeping cholesterol levels lower than 200mg/dL is difficult to trump, so despite the evidence presented earlier we'll go with the flow and pretend to want to keep cholesterol levels in check.
Niacin is the king of lowering cholesterol. Like many natural bioactives, it lowers LDL cholesterol. What sets niacin apart from the competition is that it also increases HDL cholesterol.29 Indeed, compared even to statin drugs, niacin comes out on top as statins are effective in only lowering LDL cholesterol. Niacin, on the other hand, is the most potent compound available for lowering plasma levels of triglycerides and raising HDL levels.30 Even the pharmaceutical industry advocates taking niacin concurrently with statins.31 To be sure, therapeutic doses of niacin range between 1,000 and 1,500mg/day whereas the recommended daily allowance is 14 to 16mg/day and food-product developers are hard-pressed to put into products any more than that.
Sterols are derived from natural vegetable oils such as corn and soy. Sterols and stanols have an FDA health claim to lower cholesterol levels by reducing cholesterol absorption at dosage levels of 0.8g/day. Although they have been seen to be particularly effective when incorporated into fat matrices, phytosterols have been combined with other beneficial dietary components including fish and olive oils, psyllium, and beta-glucan to enhance their effect on risk factors of cardiovascular disease.32
Studies show that 1.3g/day of plant sterol esters or 3.4g/day of plant stanol esters in the diet are needed to show a significant, 10 per cent, cholesterol-lowering effect. In order to qualify for this health claim, a food must contain at least 0.65g of plant sterol esters per serving or at least 1.7g of plant stanol esters per serving.
Sterols' effects are enhanced with diet or drug interventions: eating foods low in saturated fat and cholesterol and high in stanols or sterols can reduce LDL by 20 per cent, and adding sterols to statin drugs is more effective than doubling the statin drugs.33 The claim must specify that the daily dietary intake of plant sterol esters or plant stanol esters should be consumed in two servings eaten at different times of the day with other foods.
Red-yeast rice molecules are biodentical to statin drugs, making them effective, scientifically, in lowering LDL cholesterol levels.34 But they don't work at all effectively at lowering LDL cholesterol levels from a regulatory standpoint. This is because the drug arrived on the market first and any subsequent supplement is out in the cold.
The upshot is that products containing red-yeast rice cannot suggest in any way that the product is useful for heart health. Now, for supplements at least, the answer seems to be that savvy retailers know the score and shelve red-yeast rice products in their cardio-health section (wink, wink). Some products contain only red-yeast rice, while others make it easier for consumers by combining it with other ingredients perceived to be heart healthy, such as fish oils. Again, you might consider formulating a quality combination product with ingredients that target various markers of cardio health. Indeed, a recent Mayo Clinic randomized 12-week trial found a combination of red-yeast rice and fish oils were just as effective as statin drugs for lowering LDL cholesterol.35
Soy is the poster child for the market benefits an ingredient can have once it receives an FDA-minted health claim. Lately, however, soy's fortunes have fallen as its efficacy in lowering cholesterol levels has come into question. This arose from an October 2008 meta-analysis that found an average of 70mg/day of soy isoflavones had no effect on cholesterol levels in postmenopausal women.36 If nothing else, soy consumption improves blood lipids because soy replaces the harmful fats that would otherwise be consumed in red meat — sort of subtraction by replacing.
Speaking of replacing, an interesting randomised, crossover clinical trial was undertaken with 42 postmenopausal women with metabolic syndrome. Participants consumed either a control diet (the Dietary Approaches to Stop Hypertension, DASH), a soy-protein diet, or a soy-nut diet, each for eight weeks. Red meat in the DASH period was replaced by either soy protein or soy nuts. The soy-nut regimen decreased LDL cholesterol more than did the soy-protein period (-5 per cent compared to -0.6 per cent).37 This study showcases interesting formulation possibilities by combining soy with other heart-healthy foods — nuts in this case, and walnuts and pecans both have health claims. [See sidebar for more on health claims.]
Blood pressure and beyond
Coenzyme Q-10 is one of those ingredients that ought to be prescribed every time a physician writes a scrip for statin drugs, which deplete the heart of the nutrient. (Probiotics with antibiotic prescriptions is another obvious example.) Co-Q10 powers mitochondria, the cell's power plant, and it accumulates in particular in the heart muscle. What's more, it can lower blood pressure. In a six-month, placebo-controlled trial with 74 diabetic patients, 200mg/day of co-Q10 lowered 24-hour blood pressure.38 A similar human trial, this one for 12 weeks, with 74 diabetics found 200mg/day of co-Q10 improved blood pressure and long-term glycaemic control.39
Dairy makes a prime functional-ingredient delivery system for all manner of health benefits. Milk proteins, peptides, probiotic lactic-acid bacteria, calcium and other minerals can significantly reduce blood pressure. Fermented dairy products and probiotic bacteria decrease the absorption of cholesterol.40 A year-long 2008 human study investigating whether a glycomacropeptide (GMP)-enriched whey supplement could promote satiety and weight loss more than skim milk found no significant difference on weight loss. However, researchers did discover the whey led to decreases in total and LDL cholesterol, triacylglycerols, glucose, insulin, and systolic and diastolic blood pressure after both six and 12 months, as well as increases in HDL cholesterol at 12 months.41
Whole grains are marketed to great benefit in cereals and breads. In the Nurse's Health Study, those who had a median intake of 2.7 servings of whole grains a day experienced half the risk of ischemic stroke and a 30 per cent risk reduction of coronary artery disease.42 Another study found those with the highest fibre intake had the lowest diastolic blood pressure.43 Cereal manufacturers have clearly capitalised on this data — sometimes to a questionable degree. After all, can chocolate-frosted sugar bombs with whole grains really be good for heart health?
OPCs (oligomeric procyandins) are some of the most abundant polyphenolic substances in the plant kingdom. OPCs such as grape-seed extract and crataegus also house vasodilatory and blood pressure-modulating effects.
Pycnogenol, the French maritime pine bark (Pinus maritime), is another form of OPC that has been shown to help relax the vasculature, enhance microcirculation by increasing capillary permeability, and cut cholesterol levels.44,45
Sodium is finally being fingered by regulators as the insidious agent causing high blood pressure. Formulators are quick on the draw, developing low-sodium soups (probably the worst food culprit) and other products. A February 2009 study confirmed sodium raises blood pressure. In the two-week study of 29 overweight, normotensive subjects, the dieters consuming one third the sodium had significantly lower systolic blood pressures of 112mm Hg, compared with 117mm Hg. They also scored 4.89 per cent compared to 3.37 per cent in flow-mediated dilation scores, a marker of vascular relaxation.46
Select suppliers: Broad array of ingredients targets cardiovascular health
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