Sense and Nonsense of Dietary Supplements

Scientific evaluation of Cardiovascular health benefits of dietary supplements


April 24, 2013
by w.eijgelaar

Omega 3 Poly Unsaturated Fatty Acids (Fish oil, Krill oil, Plant sterols)

The human body can make most of the types of fats it needs from other fats or raw materials. That isn’t the case for omega-3 fatty acids. These are essential fats—the body can’t make them from scratch but must get them from food. Foods high in Omega-3 include fish, vegetable oils, nuts (especially walnuts), flax seeds, flaxseed oil, and leafy vegetables.

A whole book can be written on all studies conducted to the beneficial effects of Omega 3 fatty acids  (also called omega-3 fats and n-3 fats) on age related diseases. Three omega 3 fatty acids are known. What makes omega-3 fats special? They are an integral part of cell membranes throughout the body and affect the function of the cell receptors in these membranes. They provide the starting point for making hormones that regulate blood clotting, contraction and relaxation of artery walls, and inflammation. They also bind to receptors in cells that regulate genetic function. Likely due to these effects, omega-3 fats have been shown to help prevent heart disease and stroke, may help control lupus, eczema, and rheumatoid arthritis, and may play protective roles in cancer and other conditions.

Omega-3 fats are a key family of polyunsaturated fats. There are three main omega-3s:

  • EPA - Eicosapentaenoic acid (20 carbons and 5 double bonds) and DHA - Docosahexaenoic acid (22 carbons and 6 double bonds)  come mainly from fish, so they are sometimes called marine omega-3s.
  • ALA - Alpha Linolenic Acid (18 carbons and 3 double bonds) the most common omega-3 fatty acid in most Western diets, is found in vegetable oils and nuts (especially walnuts), flax seeds and flaxseed oil, leafy vegetables, and some animal fat, especially in grass-fed animals. The human body generally uses ALA for energy, and conversion into EPA and DHA is very limited.

The strongest evidence for a beneficial effect of omega-3 fats has to do with heart disease. These fats appear to help the heart beat at a steady clip and not veer into a dangerous or potentially fatal erratic rhythm. (1) Such arrhythmias cause most of the 500,000-plus cardiac deaths that occur each year in the United States. Omega-3 fats also lower blood pressure and heart rate, improve blood vessel function, and, at higher doses, lower triglycerides and may ease inflammation, which plays a role in the development of atherosclerosis. (1)

Several large trials have evaluated the effect of fish or fish oils on heart disease. In the Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardio (known as the GISSI Prevention Trial), heart attack survivors who took a 1-gram capsule of omega-3 fats every day for three years were less likely to have a repeat heart attack, stroke, or die of sudden death than those who took a placebo. (2) Notably, the risk of sudden cardiac death was reduced by about 50 percent. In the more recent Japan EPA Lipid Intervention Study (JELIS), participants who took EPA plus a cholesterol-lowering statin were less likely to have a major coronary event (sudden cardiac death, fatal or nonfatal heart attack, unstable angina, or a procedure to open or bypass a narrowed or blocked coronary artery) than those who took a statin alone. (3)

Most people in the developed world take in far more of another essential fat—omega-6 fats—than they do omega-3 fats. Some experts have raised the hypothesis that this higher intake of omega-6 fats could pose problems, cardiovascular and otherwise, but this has not been supported by evidence in humans. (4) In the Health Professionals Follow-up Study, for example, the ratio of omega-6 to omega-3 fats wasn’t linked with risk of heart disease because both of these were beneficial. (5) Many other studies and trials in humans also support cardiovascular benefits of omega-6 fats. Although there is no question that many people could benefit from increasing their intake of omega-3 fats, there is evidence that omega-6 fats also positively influence cardiovascular risk factors and reduce heart disease.

Current research suggests that the anti-inflammatory activity of long-chain n−3 fatty acids may translate into clinical effects. For example, there is evidence that rheumatoid arthritis sufferers taking long-chain n−3 fatty acids from sources such as fish have reduced pain compared to those receiving standard medical inflammation inhibitors such as NSAIDs. Fish oils also appear to reduce ADHD-related symptoms in some children. Double blind studies have shown "medium to strong treatment effects of omega 3 fatty acids on symptoms of ADHD".

A number of studies show that reduced intake of omega-3 fatty acids is associated with increased risk of age related cognitive decline or dementia, including Alzheimer's disease. Scientists believe the omega-3 fatty acid DHA is protective against Alzheimer's disease and dementia.

The beneficial effects of omega 3 fatty acids on cancer are low. A 2010 study of 3,081 women suffering from breast cancer was done to research the effects of polyunsaturated fats on breast cancer. It demonstrated that the consumption of high amounts of long chain omega-3 polyunsaturated fats from food produced a 25% reduced risk of additional breast cancer events. These women were also shown to have reduced risk of “all-cause mortality.” Consumption of polyunsaturated fats through fish oil supplements was not shown to decrease risk of recurring breast cancer events. Other studies also did not show beneficial effects of omega 3 fatty acids on cancer risk. Researchers are taking a hard look at a different sort of balance, this one between possible effects of marine and plant omega-3 fats on prostate cancer. Results from the Health Professionals Follow-up Study and others show that men whose diets are rich in EPA and DHA (mainly from fish and seafood) are less likely to develop advanced prostate cancer than those with low intake of EPA and DHA. (6) At the same time, some-but not all-studies show an increase in prostate cancer and advanced prostate cancer among men with high intakes of ALA (mainly from supplements). However, this effect is inconsistent. In the very large Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, for example, there was no link between ALA intake and early, late, or advanced prostate cancer. (7)


1. Leaf A. Prevention of sudden cardiac death by n-3 polyunsaturated fatty acids. J Cardiovasc Med.(Hagerstown). 2007; 8 Suppl 1:S27-29.

2. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico. Lancet. 1999; 354:447-55.

3. 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; 369:1090-98.

4. Willett WC. The role of dietary n-6 fatty acids in the prevention of cardiovascular disease. J Cardiovasc Med. (Hagerstown). 2007; 8 Suppl 1:S42-5.

5. Mozaffarian D, Ascherio A, Hu FB, et al. Interplay between different polyunsaturated fatty acids and risk of coronary heart disease in men. Circulation. 2005; 111:157-64.

6. Leitzmann MF, Stampfer MJ, Michaud DS, et al. Dietary intake of n-3 and n-6 fatty acids and the risk of prostate cancer. Am J Clin Nutr. 2004; 80:204-16.

7. Koralek DO, Peters U, Andriole G, et al. A prospective study of dietary alpha-linolenic acid and the risk of prostate cancer (United States). Cancer Causes Control. 2006; 17:783-91.




March 1, 2013
by w.eijgelaar


Policosanols are derived from the wax constituent of plants. The first policosanol supplement originates from the sugarcane that is cultured in Cuba. a well-known cholesterol lowering agent. This original product has been approved as cholesterol lowring drug in over 25 countries throughout the Caribbean and South America.

Policosanol Cholesterol lowering paradox

Studies from a single research group in Havanna, Cuba show that policosanol has strong cholesterol lowering effects ( 1 ). According to other studies from the same group, policosanol supplements are potent antioxidants, promote arterial endothelial function, inhibit platelet aggregation and thrombosis, and serve as effective treatment for intermittend claudication. Conversely, none of the more than 7 studies performed by independent research groups outside Cuba, were able to replicate these results ( 2-10 ). The Cuban researches claim that the deviating results are due to the use of different preparations. A comparison performed by the Cuban researchers that compared their original preparation with a commercial preparation called Octa-60 showed marked differences in purity and composition and a limited efficacy of Octa-60 compared to the original policosanol preparation ( 11 ). A Canadian study, however, showed that the composition of the original policosanol and other sugarcane policosanol preparations were highly similar in purity and composition ( 12 ). In addition, three of the studies that showed no effect were performed using the original policosanol preperation ( 8-10 ).


Traffic light Red Due to the striking inconsistency of the research to the cholesterol lowering activity of policosanol, using policosanol supplements for cholesterol reduction cannot be recommended. Although the majority of the studies conducted in Cuban subjects reported significant reductions in total and LDL-cholesterol concentrations between 17-21% and 21-29% respectively following consumption of policosanols from sugar cane wax, no effect on total or LDL-cholesterol concentrations was found in human intervention studies conducted in other parts of the world. In addition, the available studies showed no effect of policosanols from sugar cane wax on cholesterol absorption or on the rate of endogenous cholesterol synthesis has been observed in vivo in humans, and no evidence for a mechanism by which policosanols could exert the claimed effect.

Accepted EFSA Claims

  • No health claims have been authorized by the European Food Safety Authorisation 
Names: Policosanol, Octacosanol 
Diseases: Cardiovascular, diseases, Hypercholesterolemia 

Reference List

  1. Chen JT et al. , Meta-analysis of natural therapies for hyperlipidemia: plant sterols and stanols versus policosanol. Pharmacotherapy 25 , 171-83 (Feb, 2005).
  2. Marinangeli CP et al. , Policosanols as nutraceuticals: fact or fiction. Critical reviews in food science and nutrition 50 , 259-67 (Mar, 2010).
  3. Reiner Z, E Tedeschi-Reiner, Rice policosanol does not have any effects on blood coagulation factors in hypercholesterolemic patients. Collegium antropologicum 31 , 1061-4 (Dec, 2007).
  4. Reiner Z et al. , Effects of rice policosanol on serum lipoproteins, homocysteine, fibrinogen and C-reactive protein in hypercholesterolaemic patients. Clinical drug investigation 25 , 701-7 (2005).
  5. Greyling A et al. , Effects of a policosanol supplement on serum lipid concentrations in hypercholesterolaemic and heterozygous familial hypercholesterolaemic subjects. The British journal of nutrition 95 , 968-75 (May, 2006).
  6. Cubeddu LX et al. , Comparative lipid-lowering effects of policosanol and atorvastatin: a randomized, parallel, double-blind, placebo-controlled trial. American heart journal 152 , 982 e1-5 (Nov, 2006).
  7. Dulin MF et al. , Policosanol is ineffective in the treatment of hypercholesterolemia: a randomized controlled trial. The American journal of clinical nutrition 84 , 1543-8 (Dec, 2006).
  8. Berthold HK et al. , Effect of policosanol on lipid levels among patients with hypercholesterolemia or combined hyperlipidemia: a randomized controlled trial. JAMA : the journal of the American Medical Association 295 , 2262-9 (May 17, 2006).
  9. Kassis AN, PJ Jones, Changes in cholesterol kinetics following sugar cane policosanol supplementation: a randomized control trial. Lipids in health and disease 7 , 17 (2008).
  10. Francini-Pesenti F et al. , Sugar cane policosanol failed to lower plasma cholesterol in primitive, diet-resistant hypercholesterolaemia: a double blind, controlled study. Complementary therapies in medicine 16 , 61-5 (Apr, 2008).
  11. Castano G et al. , Comparison of the efficacy, safety and tolerability of original policosanol versus other mixtures of higher aliphatic primary alcohols in patients with type II hypercholesterolemia. International journal of clinical pharmacology research 22 , 55-66 (2002).
  12. Marinangeli CP et al. , Comparison of composition and absorption of sugarcane policosanols. The British journal of nutrition 97 , 381-8 (Feb, 2007). 
Ginkgo Biloba

March 1, 2013
by w.eijgelaar

Ginkgo Biloba

Ginkgo Biloba trees are native to China and also known as the maidenhair tree. It a unique species of tree with no close living relatives. The ginkgo biloba tree is often called a living fossil, because recognisably similar fossils have been found dating back 270 million years. Gingko Biloba is one of the most successful dietary supplements that is sold world-wide. Manufacturers claim a wide range of health benefits in the area of memory and concentration enhancement (Nootropic), dementia, circulation (claudication, Raynaud’s syndrome) and coagulation. Unfortunately the acclaimed health benefits of Ginkgo Biloba are mostly overrated or not scientifically substantiated.


According to some studies, Ginkgo Biloba can significantly improve attention in healthy individuals. Ginkgo Biloba was shown to alter the uptake and processing of neurotransmitters in the brain (i.e. serotonin, dopamine and norepinephrine), with all but the norepinephrine reuptake inhibition fading upon daily use for prolonged periods ( 1 ). A number of randomized controlled trials have also demonstrated cognitive enhancement in young ( 2-5 ) and older ( 6, 7 ) cognitively intact adults, although other studies contradict these findings ( 8-10 ). A recent well-performed meta-analysis reviewed all available studies and concluded that Ginkgo Biloba had no ascertainable positive effects on a range of targeted cognitive functions in healthy individuals ( 11


Recently, a meta-analyses of clinical trials has shown Ginkgo Biloba to be moderately effective in improving cognition in dementia patients ( 12, 13 ) but not preventing the onset of cognitive decline, dementia or Alzheimer's Disease in healthy individuals ( 14-16 ).

Bleeding and coagulation

There are several case reports available that describe excessive bleeding in relation to Ginkgo Biloba use in combination with anti-coagulant medication ( 17-19 ). A large meta-analyses of 18 randomized controlled trials containing 1985 adults, showed no effect on blood clotting (coagulation determined by ADP-induced platelet aggregation, fibrinogen concentration, aPTT, and PT) ( 20 ). This means that Ginkgo Biloba on itself does not influence coagulation, but most likely attenuates the anti-coagulation action of anti-coagulants ( 21 ). However, this is hypothesis has not been clinically validated and thus remains unclear.

Circulation, periferal artery disease, claudication and Raynaud’s syndrome

Manufacturers mostly claim that Ginko Biloba health benefits are obtained by its enhancement of perfusion of the organs, brain and periphery arteries. The meta-analysis mentioned under Coagulation, did show a positive effect of Gingko Biloba on blood perfusion. This was determined by a significant reduction in blood viscosity ( 20 ). However, a recent study showed Ginkgo Bilioba has no significant effect on the symptoms of Raynaud’s Disease ( 22 ). Meta-analyses of 14 studies with 739 participants did conclude that  Ginkgo Biloba has beneficial effects against the symptoms of claudication. However it also reports that no evidence is available that these effects are clinically significant ( 23-25 ).


Traffic light Red Evidence is lacking to support the use of Ginkgo Biloba supplements by healthy individuals to prevent memory loss, impaired cognitive functioning, dementia or Alzheimer’s Disease. It does moderately improve cognitive functioning in dementia patients though.

The use of Ginkgo Biloba to improve attention is unsubstantiated. 

Traffic Light Orange The effects of Gingko Biloba consumption on the reduction of blood viscosity and the symptoms of peripheral artery disease have been shown. However, it is questionable whether these effects are clinically relevant in reducing cardiovascular disease risk.

Based on the scientific data available, Ginkgo Biloba supplements cannot be recommended for healthy individuals and has to be avoided when using anticoagulants.

Accepted EFSA Claims

  • No health claims have been authorized by the European Food Safety Authorisation
Names: Gingko Biloba, Gingko, Bai Guo, Gingkolides 
Diseases: Periferal artery disease, Claudication, Alzheimers Disease, Raynaud’s Syndrome 

Reference List  

  1. Fehske CJ et al. , Ginkgo biloba extract (EGb761) influences monoaminergic neurotransmission via inhibition of NE uptake, but not MAO activity after chronic treatment. Pharmacological research : the official journal of the Italian Pharmacological Society 60 , 68-73 (Jul, 2009).
  2. Hindmarch I, [Activity of Ginkgo biloba extract on short-term memory]. Presse medicale 15 , 1592-4 (Sep 25, 1986).
  3. Rigney U et al. , The effects of acute doses of standardized Ginkgo biloba extract on memory and psychomotor performance in volunteers. Phytotherapy research : PTR 13 , 408-15 (Aug, 1999).
  4. Kennedy DO et al. , Modulation of cognitive performance following single doses of 120 mg Ginkgo biloba extract administered to healthy young volunteers. Human psychopharmacology 22 , 559-66 (Dec, 2007).
  5. Stough C et al. , Neuropsychological changes after 30-day Ginkgo biloba administration in healthy participants. The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum 4 , 131-4 (Jun, 2001).
  6. Mix JA, WD Crews, Jr., An examination of the efficacy of Ginkgo biloba extract EGb761 on the neuropsychologic functioning of cognitively intact older adults. Journal of alternative and complementary medicine 6 , 219-29 (Jun, 2000).
  7. Mix JA, WD Crews, Jr., A double-blind, placebo-controlled, randomized trial of Ginkgo biloba extract EGb 761 in a sample of cognitively intact older adults: neuropsychological findings. Human psychopharmacology 17 , 267-77 (Aug, 2002).
  8. Solomon PR et al. , Ginkgo for memory enhancement: a randomized controlled trial. JAMA : the journal of the American Medical Association 288 , 835-40 (Aug 21, 2002).
  9. Moulton PL et al. , The effect of Ginkgo biloba on memory in healthy male volunteers. Physiology & behavior 73 , 659-65 (Jul, 2001).
  10. Burns NR et al. , Ginkgo biloba: no robust effect on cognitive abilities or mood in healthy young or older adults. Human psychopharmacology 21 , 27-37 (Jan, 2006).
  11. Laws KR et al. , Is Ginkgo biloba a cognitive enhancer in healthy individuals? A meta-analysis. Human psychopharmacology 27 , 527-33 (Nov, 2012).
  12. Weinmann S et al. , Effects of Ginkgo biloba in dementia: systematic review and meta-analysis. BMC geriatrics 10 , 14 (2010).
  13. Ihl R et al. , Efficacy and safety of a once-daily formulation of Ginkgo biloba extract EGb 761 in dementia with neuropsychiatric features: a randomized controlled trial. International journal of geriatric psychiatry ,  (Dec 7, 2010).
  14. DeKosky ST et al. , Ginkgo biloba for prevention of dementia: a randomized controlled trial. JAMA : the journal of the American Medical Association 300 , 2253-62 (Nov 19, 2008).
  15. Snitz BE et al. , Ginkgo biloba for preventing cognitive decline in older adults: a randomized trial. JAMA : the journal of the American Medical Association 302 , 2663-70 (Dec 23, 2009).
  16. Schneider LS, Ginkgo biloba extract and preventing Alzheimer disease. JAMA : the journal of the American Medical Association 300 , 2306-8 (Nov 19, 2008).
  17. Gilbert GJ, Ginkgo biloba. Neurology 48 , 1137 (Apr, 1997).
  18. Bent S et al. , Spontaneous bleeding associated with ginkgo biloba: a case report and systematic review of the literature: a case report and systematic review of the literature. Journal of general internal medicine 20 , 657-61 (Jul, 2005).
  19. Jiang X et al. , Effect of ginkgo and ginger on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects. British journal of clinical pharmacology 59 , 425-32 (Apr, 2005).
  20. Kellermann AJ, C Kloft, Is there a risk of bleeding associated with standardized Ginkgo biloba extract therapy? A systematic review and meta-analysis. Pharmacotherapy 31 , 490-502 (May, 2011).
  21. Taki Y et al. , Ginkgo biloba extract attenuates warfarin-mediated anticoagulation through induction of hepatic cytochrome P450 enzymes by bilobalide in mice. Phytomedicine : international journal of phytotherapy and phytopharmacology 19 , 177-82 (Jan 15, 2012).
  22. Bredie SJ, MC Jong, No significant effect of ginkgo biloba special extract EGb 761 in the treatment of primary Raynaud phenomenon: a randomized controlled trial. Journal of cardiovascular pharmacology 59 , 215-21 (Mar, 2012).
  23. Nicolai SP et al. , From the Cochrane library: Ginkgo biloba for intermittent claudication. VASA. Zeitschrift fur Gefasskrankheiten 39 , 153-8 (May, 2010).
  24. Nicolai SP et al. , Ginkgo biloba for intermittent claudication. Cochrane database of systematic reviews , CD006888 (2009).
  25. Pittler MH, E Ernst, Ginkgo biloba extract for the treatment of intermittent claudication: a meta-analysis of randomized trials. The American journal of medicine 108 , 276-81 (Mar, 2000).
Grapes, glass and bottle

March 1, 2013
by w.eijgelaar


Resveratrol belongs to the class of flavonoids . Resveratrol has experienced a tremendous boost in popularity over the past decade. Resveratrol is marketed as the active component that is responsible for the demonstrated health benefits of red wine. However convincing scientific evidence is lacking.

There is no published evidence anywhere in the scientific literature of clinical trials that substantially demonstrate efficacy of Resveratrol in humans. There are limited human safety data. Long-term safety has not been evaluated in humans. Small trials investigated safety and dosage and efficacy but found negative results ( 1, 2 ). 


The groups of Howitz and Sinclair reported in 2003 in Nature, that resveratrol significantly extends the lifespan of the yeast Saccharomyces cerevisiae. Later studies showed that resveratrol also prolongs the lifespan of the worm, Caenorhabditis elegans, and the fruit fly, Drosophila melanogaster. In 2007, a different group of researchers were able to reproduce Sinclair's results with C. elegans, but a third group could not achieve consistent increases in lifespan of either D. melanogaster or C. elegans.

In 2006, Italian scientists obtained the first positive result of resveratrol supplementation in a vertebrate. Using a short-lived fish, Nothobranchius furzeri, with a median life span of nine weeks. They found a maximal dose of resveratrol increased the median lifespan by 56%. Compared with the control fish at nine weeks, the fish supplemented with resveratrol showed significantly higher swimming activity and better learning to avoid an unpleasant stimulus. The authors noted a slight increase of mortality in young fish caused by resveratrol.

A further study by a group of scientists, which included Sinclair, indicated resveratrol treatment had a range of beneficial effects in elderly mice, but did not increase the longevity of ad libitum–fed mice when started midlife. Later, the National Institute on Aging's Interventions Testing Program (ITP) also tested three different doses of resveratrol in mice on a normal diet beginning in young adulthood, and again found no effect on lifespan, even at doses roughly eight times higher than those that had normalized the lifespan of the high-fat-fed, obese mice in the earlier study.

Cardiovascular disease risk

Sinclair also reported resveratrol counteracted the detrimental effects of a high-fat diet in mice. Mice on the high-fat diet became obese, diabetic and exhibited a high mortality rate compared to mice fed the standard diet. Mice fed the high-fat diet plus resveratrol had a 30% lower risk of death than the mice on the high-fat diet alone, making their death rates similar to those on the standard diet. Resveratrol supplements did not change the levels of free fatty acids and cholesterol, however, which were much higher than in the mice on standard diet. However, these results have not been evaluated in human trials. A recent trial did show that a supplement containing grape extract with 8 mg resveratrol caused a decrease in hs-CRP levels of 26% after 1 year. Whereas placebo and grape extract without resveratrol did not show a reduction in hs-CRP. 


Traffic light Red There are indications of health benefits of Resveratrol in animal studies, but most are derived from one single research group led by Prof. Sinclair. Therefore there is a high chance of bias and thus Resveratrol supplements cannot be recommended based on currently available scientific evidence. Larger trials performed by independedn scientist should performed to provide the rerquired scientific evidence to support daily Resveratrol supplementation.

Reference List

  1. Boocock DJ et al. , Phase I dose escalation pharmacokinetic study in healthy volunteers of resveratrol, a potential cancer chemopreventive agent. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 16 , 1246-52 (Jun, 2007).
  2. Poulsen MM et al. , High-Dose Resveratrol Supplementation in Obese Men: An Investigator-Initiated, Randomized, Placebo-Controlled Clinical Trial of Substrate Metabolism, Insulin Sensitivity, and Body Composition. Diabetes ,  (Nov 28, 2012).



March 1, 2013
by w.eijgelaar

Cacoa (Dark Chocolate)

A novel source of flavonoids, cocoa, attracted interest in recent years. A recent meta-analysis of 20 studies involving 856 mainly healthy participants demonstrated that flavanol-rich chocolate and cocoa products have a small but statistically significant effect in lowering blood pressure by 2-3 mm Hg in the short term in people without high blood pressure. Long term studies are needed to substantiate long term blood pressure lowering effects (1). Cocoa flavonoids also showed an LDL lowering effect without affecting HDL or triglycerides, although the evidence is consistent the amount of evidence is still very limited (2).


Traffic Light Orange

Currently available evidence is still insufficient to recommend daily supplementation with cacoa. However, results are very promising and since the effects are highly similar to other flavonoid rich ingredients that have more substantial evidence of lowering blood pressure reducing cardiovascular disease risk, it is very likely that cacoa flavonoids have similar effects. Since Cacoa is a very tasty it is recommendable to replace other snacks by a small amount (~50 gram) of Bitter Dark Chocolate of at least 70% cacao, preferably with natural sweetners like Stevia. Be advised though. A new report in The Lancet medical journal says that many manufacturers remove flavanols from chocolate because of the bitter taste. As a result, some dark chocolate may contain no flavanols at all. However, they will still have the abundant fat and sugar that may counter the beneficiary effects of flavanols.

 Reference List 

  1. Ried K et al., Effect of cocoa on blood pressure. Cochrane database of systematic reviews 8, CD008893 (2012).
  2. Tokede OA et al., Effects of cocoa products/dark chocolate on serum lipids: a meta-analysis. European journal of clinical nutrition 65, 879-86 (Aug, 2011).

March 1, 2013
by w.eijgelaar


Quercetin is a flavonoid widely distributed in nature. The name has been used since 1857, and is derived from quercetum (oak forest). Foods containing quercetin include brewed, black or green tea, apples,sweet potato, watercress, red onion, broccoli, black plums and a number of berries, including cultivated blueberry, bilberry, lingonberry, cranberry, chokeberry, rowanberry and the fruit of the prickly pearcactus.

In a trial quercetin supplementation reduced systolic blood pressure and blood levels of oxLDL in 93 overweight subjects with a high-cardiovascular disease risk. Quercetin supplementation led to decreased systolic blood pressure by 2.6 mmHg in the entire study group, by 2.9 mmHg in the subgroup of hypertensive subjects and by 3.7 mmHg in the subgroup of younger adults aged 25-50 years. Quercetin significantly decreased plasma concentrations of atherogenic oxLDL, but did not affect inflammatory markers. Blood parameters of liver and kidney function, haematology and serum electrolytes did not reveal any adverse effects of quercetin. (1, 2). Remarkably Quercetin does not increase the body’s own antioxidant Uric Acid. A recent trial showed that a combination of quercetin, vitamin C, and niacin supplements did not show strong changes in cardiovascular risk factors in 1002 healthy volunteers, except form small reductions in blood pressure and cholesterol (3). This indicates that quercetine is more effective in subjects at high risk of cardiovascular disease. Unfortunately the blood pressure lowering effects were reduced upon aging, suggesting that quercetin does not help in reducing age related increases in blood pressure.


Traffic Light OrangeThus far insufficient evidence for beneficial effects of quercetin on reduction of cardiovascular disease risk are available. It is likely that quercetin consumption contributes to overall health. However, this limited evidence does not yet warrant daily quercetin supplementation.


Accepted EFSA Claims

  • No health claims have been authorized by the European Food Safety Authorisation

Reference List 

  1. Egert S et al., Quercetin reduces systolic blood pressure and plasma oxidised low-density lipoprotein concentrations in overweight subjects with a high-cardiovascular disease risk phenotype: a double-blinded, placebo-controlled cross-over study. The British journal of nutrition 102, 1065-74 (Oct, 2009).
  2. Egert S et al., Daily quercetin supplementation dose-dependently increases plasma quercetin concentrations in healthy humans. The Journal of nutrition 138, 1615-21 (Sep, 2008).
  3. Knab AM et al., Influence of quercetin supplementation on disease risk factors in community-dwelling adults. Journal of the American Dietetic Association 111, 542-9 (Apr, 2011).




March 1, 2013
by w.eijgelaar
1 Comment

Flavonoids and Polyphenols

One large class of phytonutrients is called polyphenols. There has been a lot of interest in these compounds in recent years. There are over 8000 different phenols and there are many as 14 classes. Some of the common ones are coumarins, flavonoids, phenolic acids, simple phenols, lignans, quinines, and xanthones. Over 2/3 of these polyphenols are in the class called flavonoids or bioflavonoids. Flavonoids are the most important plant pigments responsible for flower and fruit coloration producing yellow or red/blue pigmentation. The flavonoid subgroup anthocyanidins (anthocyanins) for example are the components that give berries (Blue-, choke- cran- and billberries) their specific dark blue color. Other fruits and vegetables with red or orange colors also contain anthocyanins ( 1 ). Proanthocyanidins are the principal substances in red wine that are linked to a reduced risk of coronary heart disease and to lower overall mortality ( 2 ). Proanthocyanidins, refer to a different class of flavonoids, called flavanols, in which occur PCOs (proanthocyanidin oligomers) or the more commonly known dietary supplement ingredient OPCs (oligomeric proanthocyanidins) or in more complex form the well-known tannins.

Several mechanisms of action of flavonoids in general have been described ( 3 ):

  1. Strong antioxidant induction properties. Oxidative stress has been implicated in the development of a number of conditions including cancer, arthritic disorders and cardiovascular disease.
  2. Stabilization of collagen fibers and promotion of collagen biosynthesis
  3. Decreased permeability and fragility of capillaries
  4. Inhibition of blood clotting (platelet aggregation)
  5. Reduction of inflammation by prevention of the release and synthesis of proinflammatory compounds (e.g. histamine, prostaglandins, and leukotrienes)
  6. Lower blood glucose levels 

Antioxidant role of flavonoids compared to Beta-carotin, Vitamin C and Vitamin E

Oxidative stress caused by free radicals is one of the driving forces behind ageing and the development of cardiovascular disease, dementia and cancer (Click here for more details). The importance and protective effect of daily intake of antioxidants is well known and has been scientifically proven. However, antioxidant consumption has been hyped beyond reason by dietary supplement manufacturers and the food industry. As a result, a large number of dietary supplements contain tremendous amounts of the antioxidants like vitamin C, up to doses that cause more harm than good. In addition, a wide range of “extremely powerful” anti-oxidants are currently being marketed, without significant evidence of actually improving the body’s antioxidant function. These are all misleading products that exploit the ignorance of the average consumer.

What most people don’t know is that most of the antioxidant function of the human body is not derived from the consumption of dietary antioxidants. Dietary antioxidants undeniably contribute to the body’s antioxidant function, but the most potent antioxidants are produced by the body itself. The increased antioxidant function of the human body after consumption of fruits and vegetables is mostly due to an induction of the body’s own antioxidant production by the flavonoids in those fruits and vegetables ( 4 ).

Thus manufacturers that tell you that flavonoids or OPCs are strong antioxidants are wrong! These compounds do have antioxidant properties, but blood levels of flavonoids after consumption of flavonoid rich food or dietary supplements are very low (in nanomolar range). This is due to limited uptake in the intestine (low bioavailability). Flavonoids are poorly absorbed (less than 5%), with most of what is absorbed being quickly metabolized into smaller substances. This means that antioxidant effect of flavonoids cannot be attributed to the antioxidant function of the flavonoids in the blood stream.

Recently researchers discovered that the metabolites derived from digestion of flavonoids are actually light toxic substances. Due to their toxicity these substances activate the natural antioxidants and defense of the human body, such as the very strong antioxidant uric acid. These are far more efficient than dietary antioxidants and therefore offer highly valuable protection against oxidative stress ( 5-7 ).

Please note that this does not mean that dietary intake beta-carotene, vitamin C and vitamin E is not important, but if your main goal is to increase antioxidant levels in the body flavonoids are the best option.

Dietary sources

The amounts of flavonoids and polyphenols in plant-based foods of the human diet —in particular vegetables, fruits, tea, and wine— are generally much greater than the amounts of antioxidants in these foods, such as vitamins C and E and carotenoids. Fruits and fruit juices are among the best sources of polyphenols and flavonoids in the human diet because of the high content in most fruits and the relatively large serving sizes (100–200 g). Apples provide approximately 22% of the total fruit phenols consumed per capita in the United States. A serving of apple provides about 400 mg of total phenols (expressed as gallic acid equivalents). Pears and grapes can provide as much as 300 mg total phenols per serving, and a serving of cranberries, cherries, or blueberries contains 200–400 mg. Total phenols in fruits, fruit juices or extracts, and vegetables is strongly correlated with the total antioxidant capacity of these foods. In fruits containing significant amounts of vitamin C, the antioxidant capacity often reflects both the polyphenol and the vitamin C content. Vegetables such as spinach, broccoli, and onions also provide significant amounts of polyphenols in the human diet. Other plant-derived foods and beverages further contribute to the total daily intake of polyphenols in humans. For example, tea, coffee, chocolate, wine, and beer have high antioxidant inducing capacity, which is almost exclusively due to the presence of polyphenols. In black tea, the levels of polyphenols vary depending on the amount of leaves, brewing time, and brewing temperature and usually are between 150 and 250 mg per 200-ml serving. Because of its wide consumption, coffee has been recently claimed to be the main source of polyphenols in the U.S. diet (J. Vinson, unpublished), providing 150–180 mg per 200-ml serving. In a Norwegian study of 2672 adults, coffee contributed 64% of the total daily intake of dietary antioxidants. Red wine contains 200–500 mg total phenols per 200-ml serving depending on type and varietal. The total phenol content in white wine is considerably lower, about 40–60 mg per 200-ml serving. Total phenol content in beer ranges from 50 to 100 mg in 200 ml. Dark chocolate contains about 340 mg of total phenols per 40-g serving. Considering these amounts of total phenols per serving, a well-balanced diet with the recommended nine daily servings of fruits and vegetables and moderate amounts of tea, coffee, wine, beer, or chocolate can provide well over 1000 mg of total phenols per day ( 5 ).

Cardiovascular risk

Flavonoids have emerged as potential candidates to protect against cardiovascular disease. Many recent human studies suggest that the consumption of flavonoid rich food (Strawberries, Blueberries, Red Wine) decreases the risk of cardiovascular disease mortality. Anthocyanins are a well studied subclass of flavonoids. Relatively low-dose anthocyanin interventions (mostly in the form of pomegranate juice) with patients clinically diagnosed with vascular diseases have been associated with significant reductions in heart ischemia ( 8 ), intima-media thickness (thickness of the arterial wall), blood pressure, LDL oxidation ( 9 ), lipid levels ( 10 ), and inflammatory status ( 11 ). This last study was a double-blind, placebo-controlled, parallel trial in forty-four patients who survived myocardial infraction and have received statin therapy for at least 6 months. Chokeberry flavonoid extract (Aronia melanocarpa E, containg 25% anthocyans, 50% polymeric procyanidines and 9% phenolic acids) supplementation for a period of 6 weeks significantly reduced serum 8-isoprostans by 38% and oxLDL levels by 29%, as well as the inflammatory markers hsCRP by 23% and MCP-1 levels by 29%. In addition, significant increase in the blood levels of the protective substance adiponectin and reductions in systolic and diastolic blood pressure by a mean average of 11 and 7.2 mmHg, respectively were found. A recent study by Karlsen et al. ( 12 ) showed significant improvement of risk biomarkers after supplementation with anthocyanins. Several pro-inflammatory cytokines and chemokines (compounds in the blood that indicate increased inflammation) were reduced in the blood of healthy men and women after supplementation with anthocyanins ( 13, 14 ). In view of the fact that flavonoids reduce the severity of inflammation, regardless of statins, they are a highly interesting supplementation alongside statin treatment.

A large number of cohort studies assessed the association between flavonoid intake and cardiovascular disease incidence anddeaths caused by cardiovascular disease (mortality). A recent review of existing studies revealed that associations are present between flavonoid intake and cardiovascular disease risk and mortality, but that results are not consistent ( 15 ). A meta-analysis of 6 cohort studies revealed that coronary heart disease risk decreased significantly with increased flavonoid intake. A large 16-year follow-up study in 34,489 post-menopausal women without cardiovascular disease showed that the intake of 0.2mg/day of the flavonoid classes, flavones and anthocyanins was associated with a decreased risk of cardiovascular disease ( 16 ). In another very recent study, this protective effect was substantiated ( 17 ). In 1999, a total of 38,180 men and 60,289 women, with a mean age of 70 and 69 y respectively, were included in the Cancer Prevention Study II Nutrition Cohort. During 7 years of follow-up, 1589 cardiovascular disease related deaths in men and 1182 cardiovascular disease related deaths in women occurred.  In this study men and women with total flavonoid intakes in the top (compared with the bottom) quintile had a 18% lower risk of fatal cardiovascular disease. Five flavonoid classes-anthocyanidins, flavan-3-ols, flavones, flavonols, and proanthocyanidins-were individually associated with lower risk of fatal cardiovascular disease ( 18 ). Several other large cohort studies showed that daily moderate red wine consumption resulted in reduced CVD risk ( 19-21 ). These effects are often attributed to the antioxidant inducing
properties of flavonoids.


Traffic Light Green

Flavonoids and its subcalsses have a proven effect on the body’s antioxidant production, thereby strongly increasing the antioxidant capacity of the body. This results in a wide range of health benefits that are mostly related to reduced inflammation and improved antioaxidant function. However, not all health benefits are adequately proven, though the reduction of cardiovascular disease risk and mortality of cardiovascular disease in individuals with high flavonoid consumption is. Therefore consumption of additional flavonoids on top of a healthy diet is recommended to reduce cardiovascular disease risk, while potentially inducing a wide range of other health benefits. It should be noted however, that not all flavonoids have similar effects and efficacy. Therefore one should be weary of supplements containing one single flavonoid substance.

Accepted EFSA Claims

  • No health claims have been authorized by the European Food Safety Authorisation
Names: Flavonoids, Polyphenols, Flavones, Flavonols, Flavanoids, Flavan-3-ols (or catechins), Flavanones, Anthocyanidins, Proanthocyanidins, Procyanidins,  
Diseases: Cardiovascular disease, Cancer, Hypercholesterolemia, Angina pectoris, Ischemic heart disease, Peripheral artery disease, High blood pressure

Reference List   

  1. Markham ØMAaKR, Ed., Flavonoids: Chemistry, Biochemistry and Applications ,  (CRC Press 2005), pp. 471 -551.
  2. Corder R et al. , Oenology: red wine procyanidins and vascular health. Nature 444 , 566 (Nov 30, 2006).
  3. Havsteen B, Flavonoids, a class of natural products of high pharmacological potency. Biochemical pharmacology 32 , 1141-8 (Apr 1, 1983).
  4. Hertog MG et al. , Intake of potentially anticarcinogenic flavonoids and their determinants in adults in The Netherlands. Nutrition and cancer 20 , 21-9 (1993).
  5. Lotito SB, B Frei, Consumption of flavonoid-rich foods and increased plasma antioxidant capacity in humans: cause, consequence, or epiphenomenon? Free radical biology & medicine 41 , 1727-46 (Dec 15, 2006).
  6. Wallace TC, Anthocyanins in cardiovascular disease. Advances in nutrition 2 , 1-7 (Jan, 2011).
  7. Godycki-Cwirko M et al. , Uric acid but not apple polyphenols is responsible for the rise of plasma antioxidant activity after apple juice consumption in healthy subjects. Journal of the American College of Nutrition 29 , 397-406 (Aug, 2010).
  8. Sumner MD et al. , Effects of pomegranate juice consumption on myocardial perfusion in patients with coronary heart disease. The American journal of cardiology 96 , 810-4 (Sep 15, 2005).
  9. Aviram M et al. , Pomegranate juice consumption for 3 years by patients with carotid artery stenosis reduces common carotid intima-media thickness, blood pressure and LDL oxidation. Clinical nutrition 23 , 423-33 (Jun, 2004).
  10. Gorinstein S et al. , Red grapefruit positively influences serum triglyceride level in patients suffering from coronary atherosclerosis: studies in vitro and in humans. Journal of agricultural and food chemistry 54 , 1887-92 (Mar 8, 2006).
  11. Naruszewicz M et al. , Combination therapy of statin with flavonoids rich extract from chokeberry fruits enhanced reduction in cardiovascular risk markers in patients after myocardial infraction (MI). Atherosclerosis 194 , e179-84 (Oct, 2007).
  12. Karlsen A et al. , Anthocyanins inhibit nuclear factor-kappaB activation in monocytes and reduce plasma concentrations of pro-inflammatory mediators in healthy adults. The Journal of nutrition 137 , 1951-4 (Aug, 2007).
  13. Kelley DS et al. , Consumption of Bing sweet cherries lowers circulating concentrations of inflammation markers in healthy men and women. The Journal of nutrition 136 , 981-6 (Apr, 2006).
  14. Scarabelli TM et al. , Targeting STAT1 by myricetin and delphinidin provides efficient protection of the heart from ischemia/reperfusion-induced injury. FEBS letters 583 , 531-41 (Feb 4, 2009).
  15. Peterson JJ et al. , Associations between flavonoids and cardiovascular disease incidence or mortality in European and US populations. Nutrition reviews 70 , 491-508 (Sep, 2012).
  16. Mink PJ et al. , Flavonoid intake and cardiovascular disease mortality: a prospective study in postmenopausal women. The American journal of clinical nutrition 85 , 895-909 (Mar, 2007).
  17. Kay CD et al. , Relative impact of flavonoid composition, dose and structure on vascular function: A systematic review of randomised controlled trials of flavonoid-rich food products. Molecular nutrition & food research 56 , 1605-16 (Nov, 2012).
  18. McCullough ML et al. , Flavonoid intake and cardiovascular disease mortality in a prospective cohort of US adults. The American journal of clinical nutrition 95 , 454-64 (Feb, 2012).
  19. Di Castelnuovo A et al. , Meta-analysis of wine and beer consumption in relation to vascular risk. Circulation 105 , 2836-44 (Jun 18, 2002).
  20. van Velden DP et al. , Red wines good, white wines bad? Redox report : communications in free radical research 7 , 315-6 (2002).
  21. Renaud S, M de Lorgeril, Wine, alcohol, platelets, and the French paradox for coronary heart disease. Lancet 339 , 1523-6 (Jun 20, 1992).


Hydrastis Canadensis

March 1, 2013
by w.eijgelaar


Berberine is a strongly yellow colored quaternary ammonium salt that is found in Berberis plants (e.g. Oregon grape, barberry, and tree turmeric), goldenseal and Chinese goldthread. Berberine is usually found in the roots, rhizomes, stems, and bark. Many studies have shown berberine has various beneficial effects on the cardiovascular system, such as cholesterol lowering, significant anti-inflammatory activities and reduction of blood glucose levels similar to anti-diabetic medication (Metformin and Rosiglitazone).



Clinical studies reveal that Berberine reduces total cholesterol, LDL-C and triglyceride levels by 15-18%, 17-21% and 21-36% respectively ( 1-4 ). The lipid lowering effect of Berberine is different from and complementary to statins as was shown in animal studies ( 5 ). Berberine leads to an increase in LDL receptor by reducing its breakdown, leading to increased uptake of LDL from the blood by the liver. Several successful clinical studies involving in total 2025 participants have been performed to determine the protective effect of a combination of Berberine, Red Yeast Rice and Policosanol to cardiovascular disease risk ( 6-9 ). These studies showed significantly lowering of total cholesterol (17-20%), LDL-C (23.3-31%), triglycerides (13%) and insulin resistance (10%), and a relative increase in HDL levels in patients with elevated cholesterol levels. This result was associated with improved endothelial function ( 7, 10 ).


Berberine increases insulin receptor (InsR) expression and improves insulin sensitivity ( 11 ). A study in 79 participants with elevated blood glucose levels, showed that Berberine significantly lowered fasting blood glucose and lowered levels of the diabetes marker hemoglobin A(1c) (HBA1c) and insulin. In this study the blood glucose- and HBA1c-lowering efficacies of Berberine were similar to those of the well-known diabetes medication Metformin and Rosiglitazone. Berberine also lowered fasting blood glucose effectively in 35 chronic hepatitis B and hepatitis C patients with type 2 diabetes or impaired fasting glucose. Liver function was improved greatly in these patients by showing reduction of liver enzymes ( 3 ). This was confirmed in another study in which HBA1c decreased from 8.1% to 7.3%. Fasting plasma insulin and insulin resistance index were reduced by 28.1% and 44.7% (P<.001), respectively. In addition, the glucose disposal rate was increased and thus the insulin resistance decreased after berberine treatment ( 1, 2 ).

Heart failure and arrhythmias

Congestive heart failure is a condition in which the heart's function as a pump is inadequate to deliver oxygen rich blood to the body. A study from 1988 showed in a small number of 12 patients with refractory congestive heart failure that continuous intravenous injection of a high dose Berberine resulted in strongly increased heart function and reduced vascular resistance ( 12 ). These results were confirmed in a more recent study from 2003. This study showed Berberine improved quality of life and heart function and decreased mortality in 156 patients with congestive heart failure ( 13 ).


Traffic Light GreenBerberine has strong cholesterol lowering properties while it improves insulin sensitivity and lowers blood glucose levels. Therefore Berberine can be recommended as dietary supplement to reduce risk of cardiovascular disease. Although less convincing, the evidence proposing effects of Berberine supplementation on heart function and endothelial function (improved flow mediated dilatation, reduced vascular resistance) further substantiates the recommendation of Berberine for cardiovascular risk reduction.

Always discuss with your physician if you are using other medications, as Berberine might interact with required dosing. Berberine should never be used when pregnant or breastfeeding, as it can cause uterine contractions and induce labor.

Accepted EFSA Claims

  • No Health Claims have been submitted to EFSA
Names: Berberine 
Diseases: Cardiovascular disease, Hypercholesterolemia, Diabetes 

Reference List 

  1. Yin J et al. , Efficacy of berberine in patients with type 2 diabetes mellitus. Metabolism: clinical and experimental 57 , 712-7 (May, 2008).
  2. Zhang Y et al. , Treatment of type 2 diabetes and dyslipidemia with the natural plant alkaloid berberine. The Journal of clinical endocrinology and metabolism 93 , 2559-65 (Jul, 2008).
  3. Zhang H et al. , Berberine lowers blood glucose in type 2 diabetes mellitus patients through increasing insulin receptor expression. Metabolism: clinical and experimental 59 , 285-92 (Feb, 2010).
  4. Kong W et al. , Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins. Nature medicine 10 , 1344-51 (Dec, 2004).
  5. Kong WJ et al. , Combination of simvastatin with berberine improves the lipid-lowering efficacy. Metabolism: clinical and experimental 57 , 1029-37 (Aug, 2008).
  6. Marazzi G et al. , Long-term effects of nutraceuticals (berberine, red yeast rice, policosanol) in elderly hypercholesterolemic patients. Advances in therapy 28 , 1105-13 (Dec, 2011).
  7. Affuso F et al. , Effects of a nutraceutical combination (berberine, red yeast rice and policosanols) on lipid levels and endothelial function randomized, double-blind, placebo-controlled study. Nutrition, metabolism, and cardiovascular diseases : NMCD 20 , 656-61 (Nov, 2010).
  8. Affuso F et al. , A nutraceutical combination improves insulin sensitivity in patients with metabolic syndrome. World journal of cardiology 4 , 77-83 (Mar 26, 2012).
  9. Trimarco B et al. , Clinical evidence of efficacy of red yeast rice and berberine in a large controlled study versus diet. Mediterranean journal of nutrition and metabolism 4 , 133-139 (Aug, 2011).
  10. Wang JM et al. , Berberine-induced decline in circulating CD31+/CD42- microparticles is associated with improvement of endothelial function in humans. European journal of pharmacology 614 , 77-83 (Jul 1, 2009).
  11. Gu Y et al. , Effect of traditional Chinese medicine berberine on type 2 diabetes based on comprehensive metabonomics. Talanta 81 , 766-72 (May 15, 2010).
  12. Marin-Neto JA et al. , Cardiovascular effects of berberine in patients with severe congestive heart failure. Clinical cardiology 11 , 253-60 (Apr, 1988).
  13. Zeng XH et al. , Efficacy and safety of berberine for congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. The American journal of cardiology 92 , 173-6 (Jul 15, 2003).

February 25, 2013
by w.eijgelaar


Lycopene (from the New Latin word lycopersicum for the tomato species name) is a bright red carotenoid pigment and phytochemical found in tomatoes and other red fruits and vegetables, such as red carrots, red bell peppers, watermelons, and papayas (but not strawberries or cherries). Lycopene is not an essential nutrient for humans, but is commonly found in the diet, mainly from dishes prepared from tomatoes. Lycopene has been found to possess antioxidant and antiproliferative (reduction of growth of cancer cells) properties in animal and laboratory studies, although activity in humans remains controversial. Lycopene is currently marketed as a protective agent against prostate cancer. However, conclusive evidence for this effect is lacking. What most people and manufacturers don’t know is that lycopene has positive effects on cholesterol levels and blood pressure. 


In a meta-analysis of 12 studies that investigated the effect of lycopene consumption on serum lipids, and four studies that examined its effect on blood pressure including data of 694 participants, revealed a significant cholesterol-lowering effect of lycopene for total serum cholesterol and LDL cholesterol by 10%, while HDL levels remained unchanged. This result was only achieved in the subgroup of trials using lycopene dosages of ≥25mg daily, whereas subgroup meta-analysis of trials using lower lycopene dosages was not significant ( 1 ). Another study showed that lycopene intervention reduces inflammation and improves HDL functionality in moderately overweight middle-aged individuals ( 2 ). The protective effect of Lycopene can also be deducted from a study in 1031 Finnish men aged 46-65 years of the Kuopio Ischemic Heart Disease Risk Factor (KIHD) cohort that showed that low blood levels of lycopene and/or β-carotene are associated with increased risk of sudden cardiac death ( 3-5 ). A recent study showed that lycopene inhibits 3-hydroxy-3-methylglutaryl coenzyme A (HmG-CoA) reductase in white blood cells, specifically, monocytes and macrophages, preventing foam cell formation. The HmG-CoA reductase inhibition was confirmed in another study ( 6 ). This is a similar mechanism of action statins have ( 7 ).

Oxidative stress and inflammation

A relatively small study in 25 subjects indicated that consuming Lycopene rich tomato products with a high-fat meal attenuates postprandial lipemia-induced oxidative stress and associated inflammatory response. The relevance of oxidized LDL and inflammation to vascular injury suggests a potentially important protective role of lycopene in reducing cardiovascular disease risk ( 8 ). Another study in 264 healthy women aged 31-75 years found an independent inverse relationship between serum lycopene concentration and both serum oxidized LDL levels as well as the inflammatory marker hs-CRP ( 9 ).

Blood pressure

A meta-analysis to the effect of lycopene on systolic blood pressure suggested a significant blood pressure reducing effect of 5.60 mmHg. Blood pressure reduction was more pronounced when a subgroup of trials with high blood pressure at baseline (SBP ≥ 140 mm Hg) was analyzed, with 9,35 mmHg ( 1 ). Another study in 264 healthy women aged 31-75 years found an independent inverse relationship between serum lycopene concentration and arterial stiffness ( 9 ).


A recent Cochrane meta-analysis on the protective effects against prostate cancer remains inconclusive ( 10-12 ). Three RCTs, with a total of 154 participants were included in this review. None of the studies reported data on prostate cancer mortality. All of the included studies differed with respect to design, participants included and allocation of lycopene. This clinical heterogeneity and the reported 'high' risk of bias limits the value of the meta-analyses. Meta-analysis indicated no statistical difference in PSA levels between lycopene and placebo. Only one study reported a decreased incidence of prostate cancer, 10% in the lycopene group versus 30% in control group. Another meta-analysis showed no correlation between lycopene consumption and breast cancer risk ( 13 ). Blood levels of lycopene and other caretonoids does however show significant associations with reduce breast cancer risk ( 14 ). In all there is insufficient evidence to either support, or refute the use of lycopene for the prevention of prostate cancer. Similarly, there is no robust evidence from clinical trials to identify the impact of lycopene consumption upon the incidence of prostate cancer, prostate symptoms, PSA levels or adverse events.


Lycopene has scientifically proven cholesterol lowering properties. In addition, lycopene consumption helps to reduce blood pressure. Even though the effects are moderate lycopene consumption can help to reduce cardiovascular risk factors and thus supplements containing lycopene can be recommended. As a bonus scientific studies show that lycopene might help to reduce chances of prostate cancer and potentially other cancer types. However, this has not yet been scientifically substantiated.

Accepted EFSA Claims

  • None
Names: Lycopene 
Diseases: Cardiovascular disease, hypercholesterolemia, hypertension, prostate cancer 

Reference List 

  1. Ried K, P Fakler, Protective effect of lycopene on serum cholesterol and blood pressure: Meta-analyses of intervention trials. Maturitas 68, 299-310 (Apr, 2011).
  2. McEneny J et al. , Lycopene intervention reduces inflammation and improves HDL functionality in moderately overweight middle-aged individuals. The Journal of nutritional biochemistry 24, 163-8 (Jan, 2013).
  3. Karppi J et al. , Serum beta-carotene and the risk of sudden cardiac death in men: A population-based follow-up study. Atherosclerosis ,  (Nov 8, 2012).
  4. Karppi J et al. , Serum lycopene decreases the risk of stroke in men: a population-based follow-up study. Neurology 79, 1540-7 (Oct 9, 2012).
  5. Palozza P et al. , Effect of Lycopene and Tomato Products on Cholesterol Metabolism. Annals of nutrition & metabolism 61, 126-134 (Sep 8, 2012).
  6. Palozza P et al. , Lycopene induces cell growth inhibition by altering mevalonate pathway and Ras signaling in cancer cell lines. Carcinogenesis 31, 1813-21 (Oct, 2010).
  7. Palozza P et al. , Lycopene regulation of cholesterol synthesis and efflux in human macrophages. The Journal of nutritional biochemistry 22, 971-8 (Oct, 2011).
  8. Burton-Freeman B et al. , Protective activity of processed tomato products on postprandial oxidation and inflammation: a clinical trial in healthy weight men and women. Molecular nutrition & food research 56, 622-31 (Apr, 2012).
  9. Kim OY et al. , Independent inverse relationship between serum lycopene concentration and arterial stiffness. Atherosclerosis 208, 581-6 (Feb, 2010).
  10. Ilic D et al. , Lycopene for the prevention of prostate cancer. Cochrane database of systematic reviews , CD008007 (2011).
  11. Giovannucci E, Commentary: Serum lycopene and prostate cancer progression: a re-consideration of findings from the prostate cancer prevention trial. Cancer causes & control : CCC 22, 1055-9 (Jul, 2011).
  12. Kristal AR et al. , Serum lycopene concentration and prostate cancer risk: results from the Prostate Cancer Prevention Trial. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20, 638-46 (Apr, 2011).
  13. Hu F et al. , Carotenoids and breast cancer risk: a meta-analysis and meta-regression. Breast cancer research and treatment 131, 239-53 (Jan, 2012).
  14. Aune D et al. , Dietary compared with blood concentrations of carotenoids and breast cancer risk: a systematic review and meta-analysis of prospective studies. The American journal of clinical nutrition 96, 356-73 (Aug, 2012).

February 25, 2013
by w.eijgelaar

Coenzyme Q10

Coenzyme Q10 is found in high concentrations in the mitochondria (power house) of every cell, it is involved in the energy metabolism (electron transport) of cells. As an energy (electron) carrier, the CoQ10 molecule is continually going through an oxidation-reduction cycle. As it accepts electrons, it becomes reduced (Ubiquinol) and becomes oxidized again (Ubiquinone) as it gives up electrons. As such it is a powerful antioxidant that prevents oxidative stress caused by our body’s energy metabolism. Because nearly all cellular functions depend on an adequate energy supply, CoQ10 deficiency is felt by all cells and particularly by those with high energy consumption, such as cardiac muscle cells, nerve cells and cells of the immune system.

CoQ10 can be synthesised by the body and therefore there is no need for CoQ10 in diets of healthy individuals. There are, however, a number of reported health benefits that can be achieved in populations with either hypertension, heart failure, dementia or people that take statins. Below the specific cardiovascular disease related health benefits of CoQ10 will be summarized.


Two meta-analyses one consisting of 3 clinical trials containing a total of 96 participants and one of 12 trials and 362 patients showed that treatment with CoQ10 in subjects with high blood pressure resulted in mean decreases in 11-17 mmHg in systolic and 7-10 mmHg in diastolic blood pressure without significant side effects ( 1, 2 ). A third meta-analysis concluded that favourable effects of CoQ10 on heart function (ejection fraction, exercise tolerance, cardiac output, and stroke volume) have been demonstrated in the literature, but that further research is needed to recommend CoQ10 as medical therapy ( 3 ).

Endothelial dysfunction

Endothelial dysfunction is one of the main causes of hypertension and has a role in atherosclerotic plaque development. In a recent meta-analysis of 5 clinical trials with 194 patients concluded that CoQ10 supplementation is associated with significant improvement in endothelial function ( 4 ).

Reduce side effects of statin treatment

Statin therapy effectively reduces the bodies cholesterol production by inhibiting Hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase. However this enzyme is also responsible for the production of CoQ10. Studies have shown that CoQ10 levels are significantly reduced upon statin treatment ( 5-10 ). More and more studies demonstrate that CoQ10 supplementation can help to reduce side effects of statin treatment, most importantly myalgia and myopathy (muscle aches, rhabdomyalysis). Several studies have demonstrated reduced side effects of statin treatment after CoQ10 supplementation ( 11-14 ). However, some studies report no reduction of myalgia upon CoQ10 supplementation alongside statin treatment ( 15, 16 ). It must be noted that in these studies either the levels of myalgia were very low or the bioavailability of the supplement was not tested by measuring coenzyme Q10 blood levels. Thus far, no large clinical trials have confirmed this theory.

Noteworthy, the pharmaceutical company Merck that markets simvastatin under the trade name Zocor, also believed in the benefits of CoQ10 supplementation alongside statin treatment. They even filed a patent to protect the pharmaceutical use of CoQ10 to reduce statin induced myopathy.

Patent: Coenzyme Q10 with HMG-CoA reductase inhibitors, EP0383432B1.

Cholesterol lowering

There is no scientific evidence of a cholesterol lowering effect of coenzyme Q10.


Traffic light Red Based on the available scientific evidence CoQ10 supplements cannot be recommended to healthy individuals.


Traffic Light Green

However, it can be recommended to lower blood pressure in people with high blood pressure and is an important measure to reduce the most common side effect of statin use, myopathy (Muscle aches).


   Accepted EFSA Claims

  • None
Names: Coenzyme Q10, Co-Q10, Q10, Ubiquinol, Ubiquinone  
Diseases: Cardiovascular disease, muscle ache, statin side effects 

Reference List

  1. Ho MJ et al. , Blood pressure lowering efficacy of coenzyme Q10 for primary hypertension. Cochrane database of systematic reviews , CD007435 (2009).
  2. Rosenfeldt FL et al. , Coenzyme Q10 in the treatment of hypertension: a meta-analysis of the clinical trials. Journal of human hypertension 21 , 297-306 (Apr, 2007).
  3. Tran MT et al. , Role of coenzyme Q10 in chronic heart failure, angina, and hypertension. Pharmacotherapy 21 , 797-806 (Jul, 2001).
  4. Gao L et al. , Effects of coenzyme Q10 on vascular endothelial function in humans: a meta-analysis of randomized controlled trials. Atherosclerosis 221 , 311-6 (Apr, 2012).
  5. Mortensen SA et al. , Dose-related decrease of serum coenzyme Q10 during treatment with HMG-CoA reductase inhibitors. Molecular aspects of medicine 18 Suppl , S137-44 (1997).
  6. Ghirlanda G et al. , Evidence of plasma CoQ10-lowering effect by HMG-CoA reductase inhibitors: a double-blind, placebo-controlled study. Journal of clinical pharmacology 33 , 226-9 (Mar, 1993).
  7. Colquhoun DM et al. , Effects of simvastatin on blood lipids, vitamin E, coenzyme Q10 levels and left ventricular function in humans. European journal of clinical investigation 35 , 251-8 (Apr, 2005).
  8. Watts GF et al. , Plasma coenzyme Q (ubiquinone) concentrations in patients treated with simvastatin. Journal of clinical pathology 46 , 1055-7 (Nov, 1993).
  9. Lamperti C et al. , Muscle coenzyme Q10 level in statin-related myopathy. Archives of neurology 62 , 1709-12 (Nov, 2005).
  10. Paiva H et al. , High-dose statins and skeletal muscle metabolism in humans: a randomized, controlled trial. Clinical pharmacology and therapeutics 78 , 60-8 (Jul, 2005).
  11. Thibault A et al. , Phase I study of lovastatin, an inhibitor of the mevalonate pathway, in patients with cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 2 , 483-91 (Mar, 1996).
  12. Kim WS et al. , Phase II study of high-dose lovastatin in patients with advanced gastric adenocarcinoma. Investigational new drugs 19 , 81-3 (2001).
  13. Caso G et al. , Effect of coenzyme q10 on myopathic symptoms in patients treated with statins. The American journal of cardiology 99 , 1409-12 (May 15, 2007).
  14. Zlatohlavek L et al. , The effect of coenzyme Q10 in statin myopathy. Neuro endocrinology letters 33 , 98-101 (Nov 28, 2012).
  15. Young JM et al. , Effect of coenzyme Q(10) supplementation on simvastatin-induced myalgia. The American journal of cardiology 100 , 1400-3 (Nov 1, 2007).
  16. Bookstaver DA et al. , Effect of coenzyme Q10 supplementation on statin-induced myalgias. The American journal of cardiology 110 , 526-9 (Aug 15, 2012).

February 22, 2013
by w.eijgelaar

Vitamin D3

Recent research investigated a wide range of health benefits that can be achieved by vitamin D supplementation. The best known are the muscular and the skeletal benefits to prevent Rickets. The internationally renowned medical institute, the Mayo Clinic, provides a very good overview of existing scientific evidence for the health benefits of vitamin D supplements .

The current International Osteoporosis Guidelines determine vitamin D insufficiency as vitamin D (25-OHD) blood levels <50 nmol/L and vitamin D deficiency if 25-OHD levels are <25 nmol/L. Based on these Guidelines the majority of people (aged >45 years) has insufficient or sub-optimal vitamin D levels ( 1-3 ). The summary below will focus on the benefits of vitamin D supplementation in cardiovascular disease prevention.

Cardiovascular disease

As reported on the website of the Mayo Clinic vitamin D deficiency or sub-optimal vitamin D levels are related with increased cardiovascular risk. Vitamin D deficiency has been linked with hypertension, immune function, myocardial infarction, stroke, and other cardiovascular-related diseases including atherosclerosis and endothelial dysfunction ( 4-8 ). A large prospective, case-controlled study of 18,000 men showed a significant correlation between low vitamin D levels and an increased risk for myocardial infarction ( 9 ). A Meta-analysis of 24 articles containing a total of 6123 cardiovascular disease cases in 65 994 participants also showed that lower vitamin D levels are linearly associated with increased cardiovascular risk and increased risk of cardiovascular disease-related mortality ( 10-14 ). A meta-analysis of 17 prospective cohort studies and randomized trials and found moderate to high doses of vitamin D supplementation may decrease the risk for cardiovascular disease. However, the amount of studies are limited and the available data is not very consistent ( 15 ). Only one study in the general population showed a very clear decrease in cardiovascular disease after vitamin D supplementation ( 16 ). In another trial of 148 women supplementation with vitamin D and calcium resulted in a significant increase in vitamin D blood levels by 72% and significant decreases in systolic blood pressure and heart rate compared with calcium supplementation alone ( 17 ). However, a different meta-analysis of 51 trials examining the effects of vitamin D supplements on cardiovascular outcomes found that although some trials showed benefits of vitamin D supplementation on risk factors, the overall trial data available could not demonstrate a consistent and statistically significant reduction in mortality or cardiovascular risk after vitamin D supplementation ( 18, 19 ). The authors do suggest a positive effect of vitamin D supplements as was seen in a different meta-analysis ( 14 ). They blame the fact that many of the included studies were not designed to evaluate cardiovascular outcomes.

Hypertension and left ventricular hypertrophy

Recent studies show low vitamin D levels are associated with hypertension and left ventricular hypertrophy. Supplementation with vitamin D provides relieve for left ventricular atrophy ( 20, 21 ). Two meta-analyses have looked at the effect of vitamin D on blood pressure levels. These meta-analyses did not demonstrate a significant effect of vitamin D on blood pressure, because the included trials were small and significant heterogeneity was observed ( 22, 23 ). A recent study in 112 patients with mild hypertension, showed that >80% had low vitamin D levels during winter and that supplementation with 75 µg of vitamin D3 on daily basis resulted in a significant reduction of systolic blood pressure by 4-7 mm Hg ( 24 ). However, better designed trials are needed to thoroughly investigate the benefits of vitamin D supplementation in lowering blood pressure. Other studies showed an association between low vitamin D levels and endothelial dysfunction and arterial stiffness ( 8 ). Supplementation of vitamin D in patients with low vitamin D levels showed significant improvement in arterial stiffness when compared with placebo. Furthermore studies have also shown an association between vitamin D supplementation and a decrease in pulse wave velocity and arterial stiffness ( 25, 26 ) and an inverse association between vitamin D levels and subclinical atherosclerosis as measured by carotid intimal-media thickness ( 27 ). These studies do suggest a beneficial effect of vitamin D supplementation on cardiovascular risk.


Traffic Light Green Studies show a chronic deficiency in vitamin D among people aged over 45, this is mostly acclaimed to the lack of exposure to sunlight and reduced vitamin D production. In addition, research shows that more and more age related disorders are associated to sub-optimal vitamin D levels. Although conclusive evidence of the health benefits of vitamin D supplements on cardiovascular disease risk is still lacking, many studies suggest positive effects. Despite the limited evidence for cardiovascular disease prevention, the recommendation of vitamin D supplements is justified by the wide spread insufficiency and the scientifically proven muscular and the skeletal health benefits. In conclusion, vitamin D supplements are recommended for people >45 years of age.


Accepted EFSA Claims

  • Vitamin D contributes to normal absorption/utilisation of calcium and phosphorus
  • Vitamin D contributes to normal blood calcium levels
  • Vitamin D contributes to the maintenance of normal bones
  • Vitamin D contributes to the maintenance of normal muscle function
  • Vitamin D contributes to the maintenance of normal teeth
  • Vitamin D contributes to the normal function of the immune system
  • Vitamin D has a role in the process of cell division
  • Calcium and vitamin D are needed for normal growth and development of bone in children
  • Vitamin D is needed for normal growth and development of bone in children.
Names: Vitamin D, cholecalciferol (vitamin D3) or ergocalciferol (vitamin D2)
Diseases: Cardiovascular disease, hypercholesterolemia, diabetes


Reference List  

  1. van Dam RM et al. , Potentially modifiable determinants of vitamin D status in an older population in the Netherlands: the Hoorn Study. The American journal of clinical nutrition 85 , 755-61 (Mar, 2007).
  2. Passeri G et al. , Calcium metabolism and vitamin D in the extreme longevity. Experimental gerontology 43 , 79-87 (Feb, 2008).
  3. Hypponen E, C Power, Hypovitaminosis D in British adults at age 45 y: nationwide cohort study of dietary and lifestyle predictors. The American journal of clinical nutrition 85 , 860-8 (Mar, 2007).
  4. McGreevy C, D Williams, New insights about vitamin D and cardiovascular disease: a narrative review. Annals of internal medicine 155 , 820-6 (Dec 20, 2011).
  5. Forman JP et al. , Plasma 25-hydroxyvitamin D levels and risk of incident hypertension among young women. Hypertension 52 , 828-32 (Nov, 2008).
  6. Forman JP et al. , Plasma 25-hydroxyvitamin D levels and risk of incident hypertension. Hypertension 49 , 1063-9 (May, 2007).
  7. Burgaz A et al. , Confirmed hypertension and plasma 25(OH)D concentrations amongst elderly men. Journal of internal medicine 269 , 211-8 (Feb, 2011).
  8. Jorde R et al. , Serum 25-hydroxyvitamin D levels are strongly related to systolic blood pressure but do not predict future hypertension. Hypertension 55 , 792-8 (Mar, 2010).
  9. Giovannucci E et al. , 25-hydroxyvitamin D and risk of myocardial infarction in men: a prospective study. Archives of internal medicine 168 , 1174-80 (Jun 9, 2008).
  10. Wang L et al. , Circulating 25-hydroxy-vitamin d and risk of cardiovascular disease: a meta-analysis of prospective studies. Circulation. Cardiovascular quality and outcomes 5 , 819-29 (Nov 1, 2012).
  11. Karakas M et al. , Low Levels of Serum 25-Hydroxyvitamin D Are Associated with Increased Risk of Myocardial Infarction, Especially in Women: Results from the MONICA/KORA Augsburg Case-Cohort Study. The Journal of clinical endocrinology and metabolism ,  (Nov 12, 2012).
  12. Lavie CJ et al. , Vitamin D status, left ventricular geometric abnormalities and cardiovascular disease. Journal of internal medicine ,  (Nov 2, 2012).
  13. Wang TJ et al. , Vitamin D deficiency and risk of cardiovascular disease. Circulation 117 , 503-11 (Jan 29, 2008).
  14. Grandi NC et al. , Vitamin D and cardiovascular disease: systematic review and meta-analysis of prospective studies. Preventive medicine 51 , 228-33 (Sep-Oct, 2010).
  15. Wang L et al. , Systematic review: Vitamin D and calcium supplementation in prevention of cardiovascular events. Annals of internal medicine 152 , 315-23 (Mar 2, 2010).
  16. Bostick RM et al. , Relation of calcium, vitamin D, and dairy food intake to ischemic heart disease mortality among postmenopausal women. American journal of epidemiology 149 , 151-61 (Jan 15, 1999).
  17. Pfeifer M et al. , Effects of a short-term vitamin D(3) and calcium supplementation on blood pressure and parathyroid hormone levels in elderly women. The Journal of clinical endocrinology and metabolism 86 , 1633-7 (Apr, 2001).
  18. Sokol SI et al. , The effects of vitamin D repletion on endothelial function and inflammation in patients with coronary artery disease. Vascular medicine 17 , 394-404 (Dec, 2012).
  19. Elamin MB et al. , Vitamin D and cardiovascular outcomes: a systematic review and meta-analysis. The Journal of clinical endocrinology and metabolism 96 , 1931-42 (Jul, 2011).
  20. Tamez H et al. , Vitamin D reduces left atrial volume in patients with left ventricular hypertrophy and chronic kidney disease. American heart journal 164 , 902-909 e2 (Dec, 2012).
  21. Fallo F et al. , Low serum 25-hydroxyvitamin D levels are associated with left ventricular hypertrophy in essential hypertension. Nutrition, metabolism, and cardiovascular diseases : NMCD 22 , 871-6 (Oct, 2012).
  22. Pittas AG et al. , Systematic review: Vitamin D and cardiometabolic outcomes. Annals of internal medicine 152 , 307-14 (Mar 2, 2010).
  23. Witham MD et al. , Effect of vitamin D on blood pressure: a systematic review and meta-analysis. Journal of hypertension 27 , 1948-54 (Oct, 2009).
  24. Larsen T et al. , Effect of cholecalciferol supplementation during winter months in patients with hypertension: a randomized, placebo-controlled trial. American journal of hypertension 25 , 1215-22 (Nov, 2012).
  25. Dong Y et al. , A 16-week randomized clinical trial of 2000 international units daily vitamin D3 supplementation in black youth: 25-hydroxyvitamin D, adiposity, and arterial stiffness. The Journal of clinical endocrinology and metabolism 95 , 4584-91 (Oct, 2010).
  26. Harris RA et al. , Vitamin D3 supplementation for 16 weeks improves flow-mediated dilation in overweight African-American adults. American journal of hypertension 24 , 557-62 (May, 2011).
  27. Carrelli AL et al. , Vitamin D deficiency is associated with subclinical carotid atherosclerosis: the Northern Manhattan study. Stroke; a journal of cerebral circulation 42 , 2240-5 (Aug, 2011).

February 22, 2013
by w.eijgelaar

Panax Ginseng

Ginseng is a well-known medical herb with a long list of acclaimed health benefits. Ginsenosides, known as ginseng saponins, are the major components of ginseng. Ginseng also contains several valuable nonsaponin components, including essential oils, antioxidants, polyacetylenic alcohols, peptides, amino acids, polysaccharides, and vitamins. A very elaborate overview of ginseng’s medical applications is given by Jae Joon Wee et al. ( 1 ).

One of the most important health effects is protection of neurons, which leads to improved learning and memory and prevention of Alzheimer’s disease. However these effects have not yet been confirmed in human trials. In case-control studies, the chance of cancer of the lip, oral cavity and pharynx, larynx, lung, oesophagus, stomach, liver, pancreas, ovary, and colorectum were significantly reduced after using ginseng supplements ( 2, 3 ). In addition ginseng has been suggested to be effective in improving psychomotor function, cognitive functioning ( 4, 5 ), erectile function ( 6 ), and pulmonary disease ( 7 ). The following in depth information will be limited to ginseng’s acclaimed health benefits for cardiovascular disease prevention.

Vasodilation (relaxing of the vessel wall), ischemic heart disease and angina pectoris (heart related chest pain)


Ginseng-based medicines and nitrates are commonly used in treating ischemic heart disease (IHD) and angina pectoris in China. Hundreds of randomized controlled trials reported in Chinese language claimed that ginseng-based medicines can relieve the symptoms of IHD by vasodilation of the coronary arteries. A systematic review containing eighteen randomized placebo controlled trials with 1549 participants investigating ginseng versus nitrates in treating IHD, demonstrated evidence that ginseng is more effective than nitrates for treating angina pectoris ( 8 ). These are highly promising results as nitrates are an accepted treatment in western countries for angina pectoris. This effect is attributed to the vasodilator function of ginseng, which has been shown in several animal studies and two small clinical trials ( 9, 10 ). The vasodilator function might also help to reduce blood pressure, but very limited evidence is available and seemingly high doses of ginseng are needed ( 9, 11, 12 ).

Antioxidant, reduction of oxidized LDL and anti-inflammation


A very recent  randomized controlled trial to the antioxidant activity of ginseng showed strong antioxidant effects in humans ( 13 ). Plasma superoxide dismutase (SOD), plasma glutathione peroxidase (GPx) and catalase activity were significantly higher after 8-week ginseng treatment. Furthermore, the DNA tail length and tail moment, both measures for DNA damage by oxidative stress were significantly reduced. More importantly, plasma levels of oxidized LDL, a major constituent to cardiovascular disease development, were reduced as well. Unfortunately study duration was short and sample size limited, making it hard to translate the study outcome to the general population.

The anti-inflammatory effects of Ginseng appear to be limited to men. A recent epidemiological study in 9,947 subjects showed that taking ginseng supplements is associated with a reduction of the inflammation risk marker for cardiovascular disease HS-CRP by 16% in men. While ginseng supplements had no effect in women ( 14 ). It is interesting to note that in a large 18 year long cohort study of 6282 subjects, Yi et al. reported an inverse association between ginseng use and total mortality, an association which was similarly limited to men ( 15 ).



Several human randomized controlled clinical trials investigating the effect of red ginseng on type 2 diabetes have been performed but remain inconclusive ( 16 ). Clinical studies with small sample sizes (10-16 patients) have reported that American ginseng lowers postprandial blood glucose in diabetic and non-diabetic patients ( 17, 18 ). Animal studies clearly show protective effects of ginseng and its components against insulin resistance and diabetes. However, confirmation in human trials is lacking ( 16 ). Therefore, more studies are required to confirm that ginseng administration decreases the dietary glycaemic index and is preventive of insulin resistance.



A recent study in postmenopausal women showed significant improvements (Kupperman index and menopause rating scale) and reduction of total cholesterol and LDL after taking American Red Ginseng ( 19 ). To achieve these effects a large dose of 3 grams per day had to be taken. Notably, no changes in cholesterol or triglycerides were detected in a study in hypertensive patients that consumed the same dose of Korean Red Ginseng ( 12 ).


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Ginseng supplements can be recommended as vasodilator. This function can help to reduce heart related chest pain (Angina Pectoris) and might be beneficial for people with starting peripheral artery disease or high blood pressure.


Traffic Light Orange

In addition, the antioxidant function and its effect on reducing the amount of oxidized LDL in the blood are very promising. Also the reported protective effects against cancer might warrant taking ginseng supplements. Unfortunately evidence for these health benefits remains limited and it is too early to definitely recommend ginseng supplements ( 20 ). 

The scientific evidence that is available, is convincing and promising. Since no side effects have been reported taking ginseng supplements can be supported from a scientific point of view.

Accepted EFSA Claims

  • No health claims have been authorized by the European Food Safety Authorisation
Names: Panax Ginseng, CA Meyer, Red Ginseng
Diseases:     Cardiovascular disease, cancer, angina pectoris, ischemic heart disease, peripheral artery disease, high blood pressure, diabetes 

Reference List

  1. Wee JJ et al. , in Herbal Medicine: Biomolecular and Clinical Aspects, IFF Benzie, S Wachtel-Galor, Eds. (Boca Raton (FL), 2011).
  2. Yun TK, Experimental and epidemiological evidence on non-organ specific cancer preventive effect of Korean ginseng and identification of active compounds. Mutation research 523-524 , 63-74 (Feb-Mar, 2003).
  3. Yun TK, Panax ginseng--a non-organ-specific cancer preventive? The lancet oncology 2 , 49-55 (Jan, 2001).
  4. Geng J et al. , Ginseng for cognition. Cochrane database of systematic reviews , CD007769 (2010).
  5. Lee MS et al. , Ginseng for cognitive function in Alzheimer's disease: a systematic review. Journal of Alzheimer's disease : JAD 18 , 339-44 (2009).
  6. Jang DJ et al. , Red ginseng for treating erectile dysfunction: a systematic review. British journal of clinical pharmacology 66 , 444-50 (Oct, 2008).
  7. An X et al. , Oral ginseng formulae for stable chronic obstructive pulmonary disease: a systematic review. Respiratory medicine 105 , 165-76 (Feb, 2011).
  8. Jia Y et al. , Could ginseng-based medicines be better than nitrates in treating ischemic heart disease? A systematic review and meta-analysis of randomized controlled trials. Complementary therapies in medicine 20 , 155-66 (Jun, 2012).
  9. Sung J et al. , Effects of red ginseng upon vascular endothelial function in patients with essential hypertension. The American journal of Chinese medicine 28 , 205-16 (2000).
  10. Jovanovski E et al. , Effects of Korean red ginseng (Panax ginseng C.A. Mayer) and its isolated ginsenosides and polysaccharides on arterial stiffness in healthy individuals. American journal of hypertension 23 , 469-72 (May, 2010).
  11. Han KH et al. , Effect of red ginseng on blood pressure in patients with essential hypertension and white coat hypertension. The American journal of Chinese medicine 26 , 199-209 (1998).
  12. Rhee MY et al. , Effect of Korean red ginseng on arterial stiffness in subjects with hypertension. Journal of alternative and complementary medicine 17 , 45-9 (Jan, 2011).
  13. Kim JY et al. , Beneficial effects of Korean red ginseng on lymphocyte DNA damage, antioxidant enzyme activity, and LDL oxidation in healthy participants: a randomized, double-blind, placebo-controlled trial. Nutrition journal 11 , 47 (2012).
  14. Kantor ED et al. , Association between use of specialty dietary supplements and C-reactive protein concentrations. American journal of epidemiology 176 , 1002-13 (Dec 1, 2012).
  15. Yi SW et al. , Association between ginseng intake and mortality: Kangwha cohort study. Journal of alternative and complementary medicine 15 , 921-8 (Aug, 2009).
  16. Kim S et al. , Red ginseng for type 2 diabetes mellitus: a systematic review of randomized controlled trials. Chinese journal of integrative medicine 17 , 937-44 (Dec, 2011).
  17. Vuksan V et al. , American ginseng (Panax quinquefolius L.) attenuates postprandial glycemia in a time-dependent but not dose-dependent manner in healthy individuals. The American journal of clinical nutrition 73 , 753-8 (Apr, 2001).
  18. Vuksan V et al. , American ginseng (Panax quinquefolius L) reduces postprandial glycemia in nondiabetic subjects and subjects with type 2 diabetes mellitus. Archives of internal medicine 160 , 1009-13 (Apr 10, 2000).
  19. Kim SY et al. , Effects of red ginseng supplementation on menopausal symptoms and cardiovascular risk factors in postmenopausal women: a double-blind randomized controlled trial. Menopause 19 , 461-6 (Apr, 2012).
  20. Karmazyn M et al. , Therapeutic potential of ginseng in the management of cardiovascular disorders. Drugs 71 , 1989-2008 (Oct 22, 2011).
Red Yeast Rice

February 22, 2013
by w.eijgelaar

Red Yeast Rice

Red yeast Rice is rice that has been fermented with the yeast Monascus Purpureus. It contains 13 different compounds called monacolins that have similar properties as the commonly known statins in cholesterol lowering medicine. They lower the bodies cholesterol production by inhibiting HMG-CoA reductase in the liver. Monacolin K is the main active component and is also known as the statin Lovastatin or Mevacor, which is sold by Merck as cholesterol lowering medicine.

Over 100 clinical trials have been performed that analyzed the cholesterol lowering properties and preventive efficacy of Red Yeast Rice. These studies all show that daily consumption of Red Yeast Rice has similar cholesterol lowering properties as medicinal statins, but with less side effects. Scientific evidence shows that daily intake of Red Yeast Rice containing 10mg monacolin K results in:

  • LDL cholesterol lowering of 7-25%
  • Relative increase of HDL up to 17%
  • Lowering of triglyceride blood levels by 10-44%
  • By lowering these risk factors the cardiovascular risk was reduced by 30-50% ( 1-12 )

Besides cholesterol lowering statins also have anti-inflammatory properties. This is a major constituent of the preventive effects of statins on cardiovascular disease. Several meta-analyses together containing over 30 clinical studies show that statin use reduces the blood levels of a number of well-known inflammatory markers ( 13, 14 ). In addition, statins have been shown to have immunomodulator effects in immune diseases like rheumatoid arthritis ( 15 ). Meta-analyses of over 20 studies show that stains help to prevent infections and infection induced mortality ( 16, 17 ).

In most studies less side effects occurred upon daily Red Yeast Rice supplementation, when compaired to daily statin therapy. A specific study that investigated the side effects of Red yeast Rice supplements in patients that did not tolerate standard statin therapy showed that 92% of the participants did endure Red Yeast Rice without side effects, but with similar cholesterol lowering ( 18 ).

Besides natural statins, Red Yeast Rice also contains a series of compounds with beneficiary effects on cardiovascular disease, such as polyunsaturated fatty acids, ergosterol, amino acids, flavonoids, alkaloids, tannins and different trace elements and minerals ( 19 ).

Traffic Light Green
Recent studies show that daily statin use results in a significant reduction of cardiovascular risk and cardiovascular related mortality (  20  ). Red yeast Rice supplements are therefore recommended for people aged >50 or with elevated cholesterol levels to prevent cardiovascular disease . However, one should always consider the quality of the supplement. High quality supplements will always indicate the amount of monacolin K present. For effective cholesterol lowering at least 10 mg monacolin K should be consumed on a daily basis.   

Always discuss with your physician if you are using other cholesterol lowering medications, as Red Yeast Rice might interact with required dosing.

Accepted EFSA Claims

  • Monacolin K from red yeast rice contributes to the maintenance of normal blood cholesterol levels. ( The claim may be used only for food which provides a daily intake of 10 mg of monacolin K from red yeast rice.)  
Names: Red Yeast Rice, RYR, Red Mold, Monascus Purpureus, Xeuzhikang, Ang Kak, Beni-koji (Japan), Cholestin, HypoCol
Diseases:  Cardiovascular, diseases, acute myocardial infarction, stroke


Reference List  

  1. Bogsrud MP et al. , HypoCol (red yeast rice) lowers plasma cholesterol - a randomized placebo controlled study. Scandinavian cardiovascular journal : SCJ 44 , 197-200 (Aug, 2010).
  2. Yang CW, SA Mousa, The effect of red yeast rice (Monascus purpureus) in dyslipidemia and other disorders. Complementary therapies in medicine 20 , 466-74 (Dec, 2012).
  3. Liu J et al. , Chinese red yeast rice (Monascus purpureus) for primary hyperlipidemia: a meta-analysis of randomized controlled trials. Chinese medicine 1 , 4 (2006).
  4. Heber D et al. , Cholesterol-lowering effects of a proprietary Chinese red-yeast-rice dietary supplement. The American journal of clinical nutrition 69 , 231-6 (Feb, 1999).
  5. Gheith O et al. , Efficacy and safety of Monascus purpureus Went rice in subjects with secondary hyperlipidemia. Clinical and experimental nephrology 12 , 189-94 (Jun, 2008).
  6. Lin CC et al. , Efficacy and safety of Monascus purpureus Went rice in subjects with hyperlipidemia. European journal of endocrinology / European Federation of Endocrine Societies 153 , 679-86 (Nov, 2005).
  7. Li JJ et al. , Impact of long-term Xuezhikang therapy on cardiovascular events in high-risk patients with nonspecific, preexisting abnormal liver tests: a post-hoc analysis from Chinese Coronary Secondary Prevention Study (CCSPS). International journal of cardiology 154 , 362-5 (Feb 9, 2012).
  8. Li JJ et al. , Long-term effects of Xuezhikang on blood pressure in hypertensive patients with previous myocardial infarction: data from the Chinese Coronary Secondary Prevention Study (CCSPS). Clinical and experimental hypertension 32 , 491-8 (2010).
  9. Li JJ et al. , Impact of Xuezhikang on coronary events in hypertensive patients with previous myocardial infarction from the China Coronary Secondary Prevention Study (CCSPS). Annals of medicine 42 , 231-40 (Apr, 2010).
  10. Li JJ et al. , Beneficial impact of Xuezhikang on cardiovascular events and mortality in elderly hypertensive patients with previous myocardial infarction from the China Coronary Secondary Prevention Study (CCSPS). Journal of clinical pharmacology 49 , 947-56 (Aug, 2009).
  11. Lu ZL et al. , [China coronary secondary prevention study (CCSPS): outcomes from analysis of coronary heart disease patients with diabetes]. Zhonghua xin xue guan bing za zhi 33 , 1067-70 (Dec, 2005).
  12. Lu ZL, [China coronary secondary prevention study (CCSPS)]. Zhonghua xin xue guan bing za zhi 33 , 109-15 (Feb, 2005).
  13. Zhang L et al. , Effects of statin therapy on inflammatory markers in chronic heart failure: a meta-analysis of randomized controlled trials. Archives of medical research 41 , 464-71 (Aug, 2010).
  14. Kinlay S, Low-density lipoprotein-dependent and -independent effects of cholesterol-lowering therapies on C-reactive protein: a meta-analysis. Journal of the American College of Cardiology 49 , 2003-9 (May 22, 2007).
  15. Kwak B et al. , Statins as a newly recognized type of immunomodulator. Nature medicine 6 , 1399-402 (Dec, 2000).
  16. Janda S et al. , The effect of statins on mortality from severe infections and sepsis: a systematic review and meta-analysis. Journal of critical care 25 , 656 e7-22 (Dec, 2010).
  17. Tleyjeh IM et al. , Statins for the prevention and treatment of infections: a systematic review and meta-analysis. Archives of internal medicine 169 , 1658-67 (Oct 12, 2009).
  18. Venero CV et al. , Lipid-lowering efficacy of red yeast rice in a population intolerant to statins. The American journal of cardiology 105 , 664-6 (Mar 1, 2010).
  19. Feng Y et al. , Natural polypill Xuezhikang: its clinical benefit and potential multicomponent synergistic mechanisms of action in cardiovascular disease and other chronic conditions. Journal of alternative and complementary medicine 18 , 318-28 (Apr, 2012).
  20. Mihaylova B et al. , The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. Lancet 380 , 581-90 (Aug 11, 2012).
Vitamin K

February 21, 2013
by w.eijgelaar

Vitamin K2

In General three types of vitamin K are defined: Vitamin K1, K2 and K3. Vitamin K1 is most commonly known and has an important role in blood coagulation (Clotting). Just recently the health benefits of Vitamin K2 have been elucidated. Vitamin K2 is also known as menachinone, menaquinone, MK-4, MK-7 and MK-9. It has an important role in bone mineralization, arterial calcification, calcification of the heart valves tissue repair and according to a recent study also in insulin response. Its biological role is to help store calcium into the proper areas in your body, such as your bones and teeth. It also plays a role in removing calcium from areas where it shouldn't be. This is confirmed by recent studies showing that anti-coagulant medication (coumarin derivates) which inhibit vitamin K function lead to an increase in osteoporosis and artery calcification (1-3). Vitamin K3, or menadione, is a synthetic form which is not recommend. Toxicity has occurred in infants injected with this synthetic vitamin K3.

Vitamin K1

There are no indications that vitamin K1 supplements provide health benefits for healthy individuals, provided adequate amounts of vegetables are consumed on daily basis ( 4 ). Since vitamin K promotes coagulation and counteracts the effects the most commonly used of anti-coagulants (coumarin derivates, like acenocoumarol, fenprocoumon en warfarine), vitamin K1 supplements should be avoided by individuals with increased risk of cardiovascular disease.

Vitamin K2
Vitamin K2 helps to reduce calcification of the arteries and heart valves. Two large Dutch studies have investigated this phenomenon.

  • A study in 4,807 elder men and women, published in 2004 in the Journal of Nutrition showed that in the group with a high dietary intake of vitamin K2 had 57% less myocardial infarctions, 52% less calcification of the aorta and 26% less overall mortality compared to the group with al low dietary intake of vitamin K2 ( 4 ).
  • After 8 years and 480 cardiovascular events, the cohort study Prospect EPIC in 16,057 women aged 49-70, showed that each increase in dietary intake of vitamin K2 by 10 microgram resulted in a risk reduction of 9% ( 5 ).

At  Geneva’s Vitafoods 2012 , Dr. Cees Vermeer, Principal Investigator at VitaK laboratory at Maastricht University, has presented data showing significant benefits for improved bone strength and prevention of cardiovascular aging with daily supplementation of the vitamin K2 supplement MenaQ7 . read more

In this long-term study, 244 healthy postmenopausal women received daily 180 µg vitamin K2 from MenaQ7 or a placebo for 3 years. The clinical measurements included bone mineral density, bone strength, vascular characteristics by ultrasound and Pulse-Wave Velocity , the latter evaluating age-related stiffening of blood vessels. MenaQ7 supplementation provided a statistically significant protection of the most vulnerable bone structures i.e. vertebrae and the hip. The MenaQ7 trial showed substantial benefits in preventing age-related stiffening of arteries resulting in increase of the Pulse Wave Velocity in the placebo group, but not in the MenaQ7-group. Most remarkably, MenaQ7 not only prevented stiffening, it also resulted in an unprecedented statistically significant improvement of vascular elasticity both measured with ultrasound techniques and Pulse Wave Velocity.

Several other well-designed clinical trials showed that vitamin K2 helps to reduce osteoporosis ( 5-10 ). In addition, there are indications that vitamin K2 helps to improve insulin response. However, this is not yet substantiated by large clinical trials ( 11 ).

Traffic Light Green
Daily supplementation with vitamin K2 is recommended to reduce the risk of cardiovascular disease. Vitamin K1 supplementation is not recommended, except for neonates up to 3 months of age.


Accepted EFSA Claims

  • Vitamin K contributes to normal blood clotting
  • Vitamin K contributes to the maintenance of normal bones
Names: Vitamin K, Vitamin K1(fyllochinon, fylloquinon, fytomenadion), Vitamin K2 (menachinon, menaquinon, abbreviated to MK), MK-4, MK-7, MK-9, Vitamine K3 (menadion)
Diseases:     Cardiovascular, diseases, acute myocardial infarction, stroke, osteoporosis, diabetes

Reference List

  1. Gage BF et al. , Risk of osteoporotic fracture in elderly patients taking warfarin: results from the National Registry of Atrial Fibrillation 2. Archives of internal medicine 166 , 241-6 (Jan 23, 2006).
  2. Schurgers LJ et al. , Oral anticoagulant treatment: friend or foe in cardiovascular disease? Blood 104 , 3231-2 (Nov 15, 2004).
  3. Spronk HM et al. , Tissue-specific utilization of menaquinone-4 results in the prevention of arterial calcification in warfarin-treated rats. Journal of vascular research 40 , 531-7 (Nov-Dec, 2003).
  4. Geleijnse JM et al. , Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam Study. The Journal of nutrition 134 , 3100-5 (Nov, 2004).
  5. Gast GC et al. , A high menaquinone intake reduces the incidence of coronary heart disease. Nutrition, metabolism, and cardiovascular diseases : NMCD 19 , 504-10 (Sep, 2009).
  6. Sato Y et al. , The prevention of hip fracture with menatetrenone and risedronate plus calcium supplementation in elderly patients with Alzheimer disease: a randomized controlled trial. The Kurume medical journal 57 , 117-24 (2011).
  7. Binkley N et al. , Vitamin K treatment reduces undercarboxylated osteocalcin but does not alter bone turnover, density, or geometry in healthy postmenopausal North American women. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 24 , 983-91 (Jun, 2009).
  8. Vermeer C et al. , Beyond deficiency: potential benefits of increased intakes of vitamin K for bone and vascular health. European journal of nutrition 43 , 325-35 (Dec, 2004).
  9. Cranenburg EC et al. , Vitamin K: the coagulation vitamin that became omnipotent. Thrombosis and haemostasis 98 , 120-5 (Jul, 2007).
  10. Beulens JW et al. , High dietary menaquinone intake is associated with reduced coronary calcification. Atherosclerosis 203 , 489-93 (Apr, 2009).
  11. Choi HJ et al. , Vitamin K2 supplementation improves insulin sensitivity via osteocalcin metabolism: a placebo-controlled trial. Diabetes care 34 , e147 (Sep, 2011).
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