Formulating cardiovascular health products that hearts will love

Formulating cardiovascular health products that hearts will love

The cardiovascular heart health market is large, both because more Americans die from heart disease than any other health condition and because there are many different ways to address it. Formulation expert Judi Quilici Timmcke, PhD, reveals the new frontier in cardiovascular nutrients.

When I first started formulating cardiovascular supplements, I was somewhat of a supplement skeptic—and still am to a certain extent. Then I had a very unusual experience at a company where I was working. A customer from Arizona had been taking large doses of coenzyme Q10 and, after three months, a few of his surgeons called our research department and asked what this man was taking for his heart. The patient had been waiting for a heart transplant and evidently no longer needed it. I was rendered speechless.

Anecdotal though it was, this piece of evidence made quite an impact on me. Amazing, and yes coenzyme Q10 is a winning ingredient, but as a formulator who wants to create unique products, where do I go from here? This category is so broad that it’s impossible to cover every aspect of cardiovascular health in one shot.

Marketing says, “Let’s go, get it done, we want a cardiovascular product!” But resistance occurs because it is a large market and there are so many nutrients with a great deal of research to evaluate. Formulators need to make a plan and begin by writing objectives for their market.

Start with the key questions:

  • What’s the primary goal? Will the product support overall heart health or will it support cardiac muscle function, maintain healthy blood pressure, antioxidant properties, or electrical transmission through the heart?
     
  • Do you want a product to help the body lower LDL (low density lipoprotein) cholesterol, Ox LDL (oxidized low density lipoprotein), or triglyceride levels, and raise HDL (high density lipoprotein)?

What follows are some key nutrients to support overall cardiovascular health and cardiac muscle tissue, and a dive into the exciting frontier of oxidized LDL (Ox LDL).

There are many subsets in the categories below and many ingredients with science to support these cardiovascular functions. We can’t possibly cover them all, but I will try to provide some interesting facts and a few stories to help you with the formulating process. One thing to remember, though—don’t forget to look for effective dosage levels that match the double-blind, placebo-controlled studies.

Ingredients for overall heart health

Coenzyme Q10, omega-3 fatty acids and vitamin E are among the ingredients in the dietary supplement industry that provide overall cardiovascular support.

The category standout: Omega-3s

The world of omega-3 fatty acids is large, with a lot of published studies, to say the least. The omega-3 fatty acids include eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and alpha-linolenic acid (ALA). Sources include both fish oils and plant oils. Krill oil, flaxseed oil, algal oil and hemp seed oil are also available. So formulators clearly have many options.

The story of omega-3s for the formulator begins by looking at omega-3 fatty acids in food. Much of the omega-3 marketing copy is based on population studies. Originally, epidemiological studies looked at the Inuit people in the Arctic and other regions who consume fatty fish with high concentrations of omega-3s. These groups have lower cardiovascular risk with higher HDL levels and reduced blood triglycerides. Individuals with abnormal cardiac arrhythmias that consume more omega-3s from their diet have a better survival rate of a myocardial infarction. This may be caused by omega-3s’ ability to increase the heart’s fibrillation threshold.1,2

In addition, a meta-analysis of clinical studies showed positive effects on blood pressure. It is wise for product formulators to review a meta-analysis since you do not have to start from scratch with your investigation. The studies have been read and evaluated providing a summary for you to assess.3

One must be careful of claims made when formulating omega-3 products in softgels and especially capsules because most of the research has been performed on omega-3s from food sources.

Runners up: Coenzyme Q10 and vitamin E

Coenzyme Q10 supports the cardiovascular system in various ways demonstrated by many clinical studies. It operates in the cell’s electron transport chain to help manufacture energy, works as an antioxidant, supports cardiovascular rhythm and blood pressure and when in low supply increases the risk of heart failure.4 CoQ10 deficiency has been evident as a predictor for myocardial infarction.5 CoQ10 research has found that it appears in LDL, which reduces atherosclerosis risk by its protection against oxidation.6 In addition, vitamin E also has demonstrated to be significantly beneficial against oxidative stress.

One double blind study administered CoQ10 or a placebo to individuals who had survived a heart attack. Compared to the placebo, the patients taking CoQ10 experienced significantly fewer heart attacks, reduced angina and reduced mortality from cardiovascular disease.7

In general antioxidant vitamins are important and it is believed that deficiencies are associated with increased angina in cardiovascular patients. One study suggests that low blood levels of vitamin E are suspected to increase the risk of angina, although more research is necessary to prove the theory.8

Ingredients for cardiac muscle tissue

A few ingredients to support heart muscle tissue are CoQ10, hawthorn and L-carnitine.

The category standout: L-carnitine

L-carnitine functions by shuttling long-chain fatty acids into the cell’s mitochondria where they are broken down for energy. Angina pectoris (chest pain) occurs when there is ischemia (insufficient blood supply to the heart muscle tissue).

L-carnitine has been used in various clinical studies to show its benefits to the heart. One randomized, placebo-controlled study administered L-carnitine in 200 patients that had exercise-induced stable angina. Patients had conventional medical therapy plus 2 grams of L-carnitine daily for 6 months. The study revealed that there was a reduced incidence of premature ventricular contractions at rest, and also improved exercise tolerance.9

In 2000, a 3-month randomized, placebo-controlled study was performed using 2 grams L-carnitine daily in 47 subjects who had chronic stable angina. Compared to placebo, L-carnitine significantly improved exercise duration and reduced the time necessary for exercise-induced ST segment changes to return to baseline.10

Runners up: CoQ10, hawthorn

CoQ10 has been shown in animal research to have a protective effect on the heart muscle tissue keeping blood flow maintained.11

Hawthorn is believed to benefit the heart muscle tissue by helping to improve blood flow to the heart and strengthening the heart’s contractions. Research has been performed demonstrating that hawthorn helps improve patients with stage II congestive heart failure.12

The new frontier: Ox LDL

Is there more to heart health than lowering LDL cholesterol and triglycerides and increasing HDL?

In the area of blood vessel support, we should be looking at the new frontier beyond cholesterol and triglyceride levels. There is more to investigate in this category prior to formulating a cardiovascular product. I encourage you to look across the horizon into the fascinating world of oxidized LDL or Ox LDL.

Elevated Ox LDL concentration increases the risk of cardiovascular disease. In fact, Ox LDL has been indicated as a more sensitive predictor for coronary artery disease (CAD) in comparison to total cholesterol and LDL cholesterol.13 Oxidized LDL causes inflammation in the arterial wall producing fatty streak formation and thereby development of plaque.

Lowering LDL is important, but the new frontier looks beyond cholesterol and triglyceride levels. One study examined LDL, HDL and triglyceride levels of patients that entered the hospital with coronary artery disease from 2000 to 2006.14 There were 231,986 individuals who entered 541 hospitals and 136,905 patient’s lipids were examined. The results showed a little less than 50 percent of the patients had optimal LDL levels (lower than 100 mg/dL); more than 50 percent of the patients had HDL levels less than 40 mg/dL and less than 10 percent of the patients had HDL levels greater than 60 mg/dL.

It would have been suspected that the majority of the cardiovascular disease patients entering the hospital would have had elevated LDL levels. LDL is an important risk factor, but there is definitely something else going on here that needs to be addressed. Investigation is underway looking at Ox LDL.

The Mediterranean diet—with foods like olive oil, fish, fruits, vegetables, vitamin C, beta-carotene, vitamin E and omega-3 fatty acids—has been shown to reduce LDL oxidation.15,16 Other ingredients include green tea, Artinia (a chitin-glucan fiber from the fungal wall of Aspergillus niger), olive extract and lycopene. Cranberry juice high in flavonoids and soy also have benefits of lowering Ox LDL.

Show-stopping ingredients

Artinia has soluble and insoluble properties, but mainly insoluble. Artinia supports the body’s natural antioxidant systems and reduces Ox LDL.17,18 A new randomized, double-blind, placebo-controlled study suggests Artinia is able to reduce Ox LDL in humans with mildly elevated LDL-cholesterol (manuscript in preparation).

Lycopene is a carotenoid in tomatoes, also found in the Mediterranean Diet. There are a few studies that have shown lycopene in food to lower Ox LDL in humans.19,20

Drinking green tea, 600 mg per day, significantly reduced Ox LDL in the blood of 20 healthy individuals who smoked.21

There have been reports showing that taking a multivitamin-mineral supplement helps to reduce LDL oxidation. In addition, supplementation with vitamin E in the form of alpha-tocopherol, along with vitamin C and beta-carotene is also effective.22,23,24 The vitamin E dosage that has been demonstrated to be helpful in reducing LDL oxidation is 400 IU per day.25,26

Select heart-health ingredient suppliers

Aker BioMarine
Superba Krill Oil is a phospholipid form of EPA and DHA omega-3 fatty acids. Fishing operation is MSC-certified.
www.akerbiomarine.com

BASF
Manufactures synthetic lycopene as well as powdered and liquid omega-3 ingredients.
www.newtrition.basf.com

Bioserae
Features a range of ingredients sourced from grapes and grapevines including resveratrol and other polyphenols.
www.bioserae.com

Bioenergy
Ribose accelerates ATP synthesis. Has been studied in cases of congestive heart failure, ischemic heart disease and cardiomyopathy. Suitable for supplements and beverages.
www.bioenergyribose.com

Cargill
CoroWise Naturally Sourced Cholesterol Reducer brand plant sterols have been clinically shown to lower cholesterol and are backed by an FDA heart health claim.
www.corowise.com

Denomega
Omega-Standard CLO is made exclusively from the hand-sorted livers of Norwegian cod to ensure the best quality possible. Contains healthy levels of vitamins A and D.
www.denomega.com

DSM Nutritional Products
ResVida is 99 percent trans-resveratrol, suitable for tablets, capsules, softgels, powdered beverages, bars, yogurts and more.
www.resvida.com

Enzymotec
Krill Oil+ brand krill oil. Phospholipid form of heart-healthy omega-3s.
www.enzymotec.com

EPAX AS
Blends of fish oils with condition-specific ratios of EPA to DHA. EPAX 6000 TG is supported by numerous clinical studies for its cardio-protective effects.
www.epax.com

Glanbia
MeadowPure flaxseed line delivers heart-healthy ALA omega-3s.
www.glanbia.com

Kaneka
Offering Kaneka QH Ubiquinol, the active antioxidant form of CoQ10.
www.kanekaqh.com

LycoRed
Lyc-O-Mato natural lycopene. Epidemiological studies support the health benefits of whole tomato and tomato extract products.
www.lycored.com

Neptune
Supplies Neptune Krill Oil, with DHA and EPA bound in a phospholipid form.
www.neptune.com

Pharmachem Laboratories/Proprietary Nutritionals
Sytrinol, a patented formula derived from citrus bioflavonoids and palm tocotrienol to support healthy cholesterol levels. Also Benexia, organic, GMP certified chia seed.
www.pharmachemlabs.com

Omega Protein
Supplies OmegaPure fish oil with EPA and DHA sourced from menhaden. Friend of the Sea certified sustainable fishery.
www.omegaproteininc.com

Pacific Rainbow International, Inc
Supplies CoQ10 in powder and water soluble powder form.
www.prinutrition.com

P.L. Thomas
MenaquinGold Natural Vitamin K2-MK7 supports arterial health through calcium mobilization.
www.plthomas.com

Polyphenolics
MegaNatural-BP grape seed extract supports healthy blood pressure and endothelial cell health.
www.meganaturalbp.com/

pTeroPure
pTeroPure Pterostilbene is shown in animal studies to promote healthy cholesterol levels, blood pressure, and lipid levels in blood stream.
www.pteropure.com

Sabinsa Corporation
Gugulipid, a natural extract derived from Commiphora mukul gum, clinically shown to lower the biomarkers of inflammation and benefit cardiovascular health and wellness.
www.sabinsa.com

The Scoular Company
CardioFuzion is a novel ingredient containing plant sterol ester, EPA and DHA.
www.scoular.com

Soft Gel Technologies
EZ Mega 3 soft gels supply an ultrapure fish oil concentrate with no fishy taste or smell.
www.soft-gel.com

Stratum Nutrition
ARTINIA is a novel vegetarian fiber ingredient for arterial health. The chitin-glucan ingredient is GRAS, non-GMO, kosher and halal.
www.stratumnutrition.com

TSI Health Sciences
Produced through a proprietary fermentation process, PEAK ATP delivers the exact molecule the human body needs to create energy.
www.tsiinc.com

Xtso Solutions
Kappa Bioscience K2VITAL brand vitamin K2 MK-7; Virun OmegaH2O water soluble omega-3s.
www.xtsosolutions.com

ZMC USA
CoQ10 for heart health, suitable for supplements.
www.zmc-usa.com

References

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2. Murnaghan MF. Effects of fatty acids on the ventricular arrhythmia threshold in the isolated heart of the rabbit". Brit J Pharmacol. 1981;909–915.

3. Appel LF, Miller ER, Sidler AJ, Whelton PK. Does supplementation of diet with fish oil reduce blood pressure? A meta-analysis of controlled clinical trials". Archives of Internal Medicine. 1993; 153 (12):1429–1438.

4. Molyneux SL, Florkowski CM, George PM, et al. Coenzyme Q10: an independent predictor of mortality in chronic heart failure. J Am Coll Cardiol. 2008;52(18):1435–1441.

5. Alleva R, Tomasetti M, Battino M, et al. The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions. Proc. Natl. Acad. Sci. U.S.A. 1995;92(20): 9388–9391.

6. Mohr D, Bowry VW, Stocker R. Dietary supplementation with coenzyme Q10 results in increased levels of ubiquinol-10 within circulating lipoproteins and increased resistance of human low-density lipoprotein to the initiation of lipid peroxidation. Biochim. Biophys. Acta. 1992;1126(3):247–254.

7. Singh RB, Wander GS, Rastogi A, et al. Randomized double-blind placebo-controlled trial of coenzyme Q10 in patients with acute myocardial infarction. Cardiovasc Drugs Ther. 1998;12:347–353.

8. Riemersma RA, Wood DA, Macintyre CC, et al. Low plasma vitamins E and C. Increased risk of angina in Scottish men. Ann N Y Acad Sci. 1989;570:291-295.

9. Cacciatore L, Cerio R, Ciarimboli M, et al. The therapeutic effect of L-carnitine in patients with exercise-induced stable angina: a controlled study. Drugs Exp Clin Res. 1991;17(4):225-235.)

10. Lyer RN, Khan AA, Gupta A, et al. L-carnitine moderately improves the exercise tolerance in chronic stable angina. J Assoc Physicians India. 2000;48(11):1050-1052.

11. Atar D, Mortensen SA, Flachs H, et al. Coenzyme Q10 protects ischemic myocardium in an open-chest swine model. Clin Investig. 1993;71:S103–S111.

12. Schmidt U, Kuhn U, Ploch M, et al. Efficacy of the Hawthorn (Crataegus) preparation LI 132 in 78 patients with chronic congestive heart failure defined as NYHA functional class II. Phytomed. 1994;1:17–24.

13. Huang H, Mai W, et al., The oxidation ratio of LDL: A predictor for coronary artery disease. Dis Markers. 2008;24: 341-349.

14. Sachdeva, A et al. Lipid levels in patients hospitalized with coronary heart disease: an analysis of 136,905 hospitalizations in Get With The Guidelines. Am Heart J. 2009 Jan;157(1):111-117.e2. Epub 2008 Oct 22.

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17. Deschamps,A, Nollevaux,G, Gautier,S, Keller,F: Managing oxidative stress with a vegetal ingredient, chitin-glucan. AgroFood. 2009;20:12-14.

18. Berecochea-Lopez A, Decorde K, Ventura E, et al. Fungal chitin-glucan from Aspergillus niger efficiently reduces aortic fatty streak accumulation in the high-fat fed hamster, an animal model of nutritionally induced atherosclerosis. J Agric Food Chem. 2009;57:1093-1098.

19. Agarwal, S, Rao AV. Tomato lycopene and low-density lipoprotein oxidation: a human dietary intervention study. Lipids. 1998; 33:981-984.

20. Bub A, Watzl B, et al. Moderate Intervention with Carotenoid-Rich Vegetable Products Reduces Lipid Peroxidation in Men. J Nutr. 2000;130: 2200-2206.

21. Lee W, Min WK, Chun S, et al. Long-term effects of green tea ingestion on atherosclerotic biological markers in smokers. Clin Biochem. 2005;38:84–8 7.

22. Earnest CP, Wood KA, Church TS. Complex multivitamin supplementation improves homocysteine and resistance to LDL-C oxidation. J Am Coll Nutr. 2003;22:400–407.

23. Bunout D, Garrido A, Suazo M, et al. Effects of supplementation with folic acid and antioxidant vitamins on homocysteine levels and LDL oxidation in coronary patients. Nutrition. 2000;16:107– 10.

24. Meraji S, Ziouzenkova O, Resch U, Esterbauer H. Enhanced plasma level of lipid peroxidation in Iranians could be improved by antioxidants supplementation. Eur J Clin Nutr. 1997;51:318– 325.

25. Jialal I, Fuller CJ, Huet BA. The effect of alpha-tocopherol supplementation on LDL oxidation. A dose-response study. Arterioscler Thromb Vasc Biol. 1995;15:190–198.

26. Princen HM, van Duyvenvoorde W, Buytenhek R, et al. Supplementation with low doses of vitamin E protects LDL from lipid peroxidation in men and women. Arterioscler Thromb Vasc Biol. 1995;15:325– 333.

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