How To Lower CRP Safely With Supplements (2024)

We recognize the medical establishment is agonizingly slow at grasping new concepts. They do wake up to scientific reality, however, when they smell an opportunity to earn tens of billions of dollars.

Life Extension members were warned long ago about the dangers of excess C-reactive protein in the blood. C-reactive protein is a marker of inflammation. Chronic inflammation, as evidenced by high C-reactive protein blood levels, is a cause of atherosclerosis.1-3 Published studies indicate that elevated C-reactive protein may be a greater risk factor than high cholesterol in predicting heart attack and especially stroke risk.4-8

There are many natural methods to lower C-reactive protein. The pharmaceutical industry favors using statin drugs: an unnatural way to reduce C-reactive protein. While statin drugs are prescribed to lower LDL (low-density lipoprotein) and total cholesterol, statin drugs also reduce heart attack and stroke risk by suppressing C-reactive protein.

A clinical study was sponsored by a pharmaceutical company to see if its patented statin drug (Crestor®) would reduce heart attack and stroke risk if given to people with moderate LDL levels, but excess C-reactive protein. The results revealed a 43% reduction in various types of vascular disease after less than two years.9

These data are impressive on the surface, but the study exposed a harsh reality that we at Life Extension have voiced alarming concern about for decades. As you will read, Crestor® significantly reduced heart attack-stroke incidence, but there were still a startling number of heart attacks and strokes in people whose LDL levels plummeted to extremely low levels. While this study may be used to aggressively promote Crestor®, it exposes the limitations of statin drugs in preventing heart disease and stroke.

This study does help validate the multipronged vascular protection program that most Life Extension members already follow, especially the comprehensive blood tests members take to uncover hidden risk factors like C-reactive protein. We don’t agree that people should start using high-dose Crestor® when safer, lower-cost, and more comprehensive approaches exist right now.

The Crestor® Study Subjects

Fat cells are a source of C-reactive protein production in the body.10,11 Corpulent people usually have C-reactive protein levels much higher than lean individuals. In order to find enough subjects with high C-reactive protein levels, participants in the Crestor® study were recruited who were significantly overweight with a median body mass index of about 28. Overweight is clinically defined as a body mass index of 25 and above.

Despite having only modest LDL elevations (median about 108 mg/dL), this group of overweight individuals was at high risk for vascular disease, as about 41% already suffered from metabolic syndrome when the study commenced. Metabolic syndrome is a constellation of risk factors that sharply elevates one’s risk for contracting a lethal disorder.

The median study subjects’ baseline C-reactive protein blood levels were 4.25 mg/L, a reading that placed them at greater risk for a host of age-related diseases including cancer, dementia, heart attack, and stroke.

High-Dose Crestor® Used

Crestor® is the most potent statin drug, compared with milder statin drugs like pravastatin and simvastatin. The 20 mg daily dose of Crestor® used in this study is on the very high side for this particular drug. In fact, the dose of Crestor® used in this study was double the recommended starting dose. This raises concern about long-term side effects, though few were reported in this relatively short-term study.

In lieu of this high-dose Crestor®, many people may find similar benefits taking 5-20 mg of simvastatin or 20-40 mg a day of pravastatin, plus natural agents to lower C-reactive protein.

The monthly cost to take Crestor® (20 mg) is $105, whereas generic simvastatin (20 mg) costs only $6.91 a month and generic pravastatin (40 mg) only $11.40 a month.

C-Reactive Protein Not Lowered Enough

Despite the very high dose of Crestor® used, median C-reactive protein levels fell only from 4.25 mg/L to 2.2 mg/L of blood. The optimal range for C-reactive protein is under 0.55 mg/L in men and under 1.5 mg/L in women.12 Crestor®, even at the relatively high dose used, fell far short of reducing C-reactive protein enough to completely eliminate this inflammatory marker as a vascular disease risk factor.

What this high dose of Crestor® did do is lower LDL from a baseline average of 108 to 55 mg/dL at the end of the study. Few statin drug studies have suppressed LDL this much. Please remember that LDL is not all bad. LDL is essential to transport cholesterol from the liver to cells that need it throughout the body. Without sufficient LDL, people will die. The problem is that no one yet knows for sure what truly optimal LDL levels are. You need enough LDL to ensure that sufficient cholesterol is delivered to the cell membranes, but not so much LDL that arterial occlusion manifests.

We believe that the 43% reduction in risk of major cardiovascular events (including heart attack, stroke, unstable angina, arterial revascularization, and death from cardiovascular causes) observed in this study was a result of suppressing both LDL and C-reactive protein levels, along with other endothelial benefits that statin drugs possess (which can also be obtained by using natural approaches). We are concerned, however, about the long-term effects of using a potent dose of a drug like Crestor®, when safer and more natural strategies are available.

Too Many Crestor® Patients Suffered “Major Cardiovascular Events”

Pharmaceutical companies have promoted statin drugs as a virtually universal remedy to prevent heart attack. According to conventional guidelines, statin drugs are to be prescribed when LDL blood levels exceed 130 mg/dL.

We at Life Extension have long argued that LDL levels should be kept below 100 mg/dL in healthy people to optimally protect against atherosclerosis (and below 70 mg/dL in certain high-risk cardiac patients).

The high dose of Crestor® used in this study pushed LDL down to a low of 55 mg/dL and it reduced C-reactive protein by 37%. The fact that a significant number of subjects taking Crestor® still suffered “major cardiovascular events” exposes the fallacy of relying only on statin drugs to maintain healthy arterial blood flow.

To put this in mathematical perspective, this study showed that if 10,000 people were not treated with Crestor® for one year’s time, there would be 136 major cardiovascular events. Based on the elevated baseline blood C-reactive protein (4.2 mg/L), the fact that LDL was over 100 mg/dL, and that 41% of these subjects had metabolic syndrome, this number of 136 cardiac events per 10,000 study subjects makes sense if no interventions are done.

This study showed that if 10,000 study subjects took high-dose Crestor® for one year, 59 major cardiovascular events would not occur (compared with 136 events that would occur if Crestor® was not taken).

What will not be disclosed in drug advertising, however, is that more than half (77 out of 136) of major cardiovascular events would occur despite the use of high-dose Crestor®. In statistical terms, while Crestor® reduced the relative risk of major cardiovascular events by 43%, the majority (57%) of cardiovascular events in this high-risk study group study would still take place!

What this means is that if you have cardiac risk factors and rely solely on a high-dose statin drug, you are still at significant risk of suffering a heart attack. In fact, 142 patients treated with high-dose Crestor® experienced a cardio-vascular event during this study.

Why Crestor® Failed 142 Patients in This Study

There are at least 17 independent risk factors involved in the development of atherosclerosis and subsequent heart attack and stroke. Statin drugs do not come close to correcting all of these risk factors. Based on the findings from this Crestor® study, it is obvious that even when LDL (and total cholesterol) is reduced to extremely low levels, too many people still suffer a major cardiovascular event.

We predict this study will eventually be used in national advertisem*nts to tout Crestor® as a panacea. An analysis of the actual study findings, however, documents the critical need to correct all known cardiovascular risk factors (including elevated LDL, total cholesterol, and C-reactive protein).

We are not vilifying the proper use of statin drugs. For many people with stubbornly high LDL and C-reactive protein levels, they represent an important weapon against arterial disease. Our emphasis is that statin drugs are not the only way to lower LDL and C-reactive protein, and they should not be relied on as the only approach to protect against atherosclerosis.

Reducing C-Reactive Protein Often Requires a Multimodal Approach

Life Extension has reviewed thousands of C-reactive protein blood test results over the years. Our consistent observation is that overweight and obese individuals have stubbornly elevated C-reactive protein levels.13 Our findings were confirmed in a recent study that showed the following:14,15

Percent with Elevated C-Reactive Protein (>1 mg/dL)

• Normal Weight Individuals 25%
• Overweight Individuals 51%
• Obese Individuals 75%

These grim findings correlate well with the increased risks of cancer,16-18 stroke,8,19 heart attack,19-23 and dementia24 that occur as people accumulate excess body fat.

In the Crestor® study, average C-reactive protein levels were 4.25 mg/L at baseline. Obese individuals can have C-reactive protein levels that are easily double this. The biological challenge in overweight people is to combat the excess C-reactive protein made directly by fat cells (adipocytes) and the C-reactive protein made in the liver in response to excess amounts of interleukin-6 expressed in abdominal fat that is dumped directly into the liver.

Since obese and overweight individuals spew out C-reactive protein from their liver and fat cells, it is often challenging to bring this lethal inflammatory compound (C-reactive protein) into safe ranges.

While we are impressed with the data from the Crestor® study showing the reduction in C-reactive protein and major cardiovascular events, our decade-long evaluation of C-reactive protein blood results prompts us to warn that it will require more than statin drugs to suppress the dangerously high C-reactive protein levels prevalent in so many individuals.

The good news is that low-cost nutrients and hormones, along with dietary changes, can work as well as statins in reducing deadly C-reactive protein.

Vitamin C Reduces C-Reactive Protein

Right after the media put Crestor® on the front pages, a study was published showing that 1,000 mg a day of vitamin C reduces C-reactive protein as well as some statin drugs.14 Needless to say, this vitamin C study received scant media coverage.

In this University of California at Berkeley study, participants who received vitamin C and started out with C-reactive protein levels greater than 2.00 mg/L had 34% lower levels compared with the placebo group after only two months.14,15

This study was done based on previous findings that vitamin C supplements reduce elevated C-reactive protein. It would have been interesting to see if the addition of 1,000 mg a day of vitamin C would have reduced the number of “major cardiovascular events” that occurred in the Crestor® study.

A Healthy Diet Significantly Reduces C-Reactive Protein

Eating too much saturated fat or high-glycemic carbohydrates increases C-reactive protein.25,26 One study showed a 39% decrease in C-reactive protein levels after only eight weeks of consuming a diet low in saturated fat and cholesterol.27 The study participants also saw reductions in their LDL, total cholesterol, body weight, and arterial stiffness.

So while you may soon see ads promoting the 37% C-reactive protein reduction in response to high-dose Crestor®, you should be aware that the same benefit has already been shown in response to healthier eating—with no drugs used.

Another study shows that eating cholesterol-lowering food works about as well as consuming a very low-fat diet plus statin drug therapy. This study showed a 33.3% reduction in C-reactive protein and 30.9% reduction in LDL in subjects eating a very low-fat diet and taking a statin drug. Those who ate the cholesterol-lowering foods showed a 28.2% reduction in C-reactive protein and a 28.6% reduction in LDL.28 This study showed that eating cholesterol-lowering foods achieved almost the same benefit as those who followed a very low-fat diet and took a statin drug.

The cholesterol-lowering foods used in this study include almonds, soy protein, fiber, and plant sterols.28 Few people can follow a rigorous low-fat diet and some people want to avoid statin drugs. Based on this study, those who need to reduce LDL and/or C-reactive protein blood levels can accomplish this by eating cholesterol-lowering foods or taking supplements such as soluble fiber powder before heavy meals.

In a study of 3,920 people, subjects who ingested the most dietary fiber were found to have a 41% lower risk of elevated C-reactive protein levels, compared with those who ate the least fiber. The doctors who conducted this study concluded:

“Our findings indicate that fiber intake is independently associated with serum CRP concentration and support the recommendation of a diet with a high fiber content.”29

There is an important take-home lesson here for those with high C-reactive protein levels that persist even after initiating statin drug therapy. You may be able to achieve significant additive benefits by making dietary modifications, taking at least 1,000 mg of vitamin C each day, and following other proven ways to quell chronic inflammatory reactions.

Sex Hormones and Inflammation in Men

Aging men are plagued with declining testosterone levels while their estrogen remains the same or even increases. This imbalance often sets the stage for a host of chronic inflammatory disorders, while increasing the amount of abdominal adiposity.

For years, we at Life Extension have advised maturing men to restore their free testosterone to youthful ranges (between 20 and 24 pg/mL of blood) and keep their estrogen from getting too high. Ideal estrogen (estradiol) levels in men have been shown to be between 20 and 30 pg/mL of blood.

We have seen countless cases of men with chronic inflammation experience a reversal of their elevated C-reactive protein (and painful symptoms) when a youthful sex hormone profile is properly restored. Independent published studies corroborate our findings that low testosterone and high estradiol predisposes aging men to chronic inflammatory status and higher C-reactive protein.30-32

Based on these findings, the overweight Crestor® study subjects could have benefited enormously if their sex hormone balance was restored to youthful ranges. It is tantalizing to think what benefits could have been shown if those who took Crestor® used these additive approaches to reduce their C-reactive protein to optimal levels.

Simple Guidelines to Protect Yourself Against Heart Attack and Stroke

At the end of this article is a reprint of our 17 “daggers aimed at the heart” diagram that represents independent risk factors associated with heart attack and stroke. Any one of these daggers can create vascular disease. Regrettably, aging people often suffer multiple risk factors (daggers aimed at their heart) that cause them to die prematurely.

Fortunately, the proper blood tests can identify risk factors unique to each individual so that corrective action can be taken before one’s heart or brain is decimated by a catastrophic vascular event.

The third article in this month’s issue discusses the 17 independent risk factors involved in vascular disease and describes the simple steps you can take to make sure that none of them causes a problem for you. As you will readily see, there is a wide range of lifestyle, nutrient, hormone, and drug choices available. If you don’t want to take drugs, plenty of natural alternatives exist. Some people will need to take drugs, however, to get into optimal ranges.

Lethal Dangers of C-Reactive Protein Elevation

Multiple studies document that a chronic inflammatory process is directly involved in the degenerative diseases of aging including cancer,89-91 dementia,92-94 stroke,95-97 visual disorders,98,99 arthritis,100-102 liver failure,103,104 and heart attack.4,105-109

Fortunately, a low-cost C-reactive protein blood test can identify whether you suffer a smoldering inflammatory fire within your body that will likely cause you to die prematurely. An abundance of scientific research provides a wide range of proven approaches to suppress chronic inflammatory reactions.33-78,110,111

The comprehensive Male and Female Blood Test Panels reveal what your C-reactive protein level is right now, along with other factors that could cause your C-reactive protein to be too high. Blood components that can spike C-reactive protein levels include high LDL,112 low HDL,113 low testosterone114 and excess estradiol (in men),115 elevated glucose,116,117 excess hom*ocysteine,118 and DHEA deficit.119

Remember, optimal blood levels of C-reactive protein are below 0.55 mg/L in men and below 1.50 mg/L in women.12 Standard reference ranges accept higher levels as normal because so many people fail to take care of themselves and thus suffer chronically high C-reactive protein levels with subsequently increased risk of heart attack,6,120-123 stroke,6-8,124 cancer,89-91 senility,125,126 etc.127

No More Heart Attacks!

The Crestor® study showed it is possible to achieve a dramatic reduction in heart attack and stroke incidence when C-reactive protein and LDL are reduced.

Yet the same study revealed that a significant number of study subjects who suffered “major cardiovascular events” were not protected by the high dose of Crestor® they took.

This proves beyond any doubt that more than cholesterol, LDL, and C-reactive protein5,128-132 are involved in the atherosclerotic process that results in heart attack and stroke being today’s leading causes of disability and death.

If one is to achieve ultimate protection against arterial disease, all of the independent risk factors (as identified in the 17 daggers aimed at the heart graphic) have to be brought under control.

We should all be grateful to live in an era when these vascular risk factors can be easily measured and corrected before a major cardiovascular event manifests!

Lowest Blood Test Prices of the Year

Once a year, Life Extension discounts the price of the popular Male or Female Blood Test Panels. The medical establishment charges around $1,000 for these comprehensive tests.

To review the many longevity factors included in the Male or Female Blood Test Panels, and how you can use the findings from your blood test to protect against age-related disease, refer to How to Circumvent 17 Independent Heart Attack Risk Factors from this issue.

When you place your blood test order, we send you a requisition form along with a listing of blood-drawing stations in your area. You can normally walk in during regular business hours for a convenient blood draw.

For longer life,

William Faloon

1. Agmon Y, Khandheria BK, Meissner I, et al. C-reactive protein and atherosclerosis of the thoracic aorta: a population-based transesophageal echocardiographic study. Arch Intern Med. 2004 Sep 13;164(16):1781-7.
2. Patrick L, Uzick M. Cardiovascular disease: C-reactive protein and the inflammatory disease paradigm: HMG-CoA reductase inhibitors, alpha-tocopherol, red yeast rice, and olive oil polyphenols. A review of the literature. Altern Med Rev. 2001 Jun;6(3):248-71.
3. Dandona P. Effects of antidiabetic and antihyperlipidemic agents on C-reactive protein. Mayo Clin Proc. 2008 Mar;83(3):333-42.
4. Ridker PM, Rifai N, Rose L, Buring JE, Cook NR. Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med. 2002 Nov 14;347(20):1557-65.
5. Montecucco F, Mach F. New evidences for C-reactive protein (CRP) deposits in the arterial intima as a cardiovascular risk factor. Clin Interv Aging. 2008;3(2):341-9.
6. Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med. 1997 Apr 3;336(14):973-9.
7. Ridker PM, Buring JE, Shih J, Matias M, Hennekens CH. Prospective study of C-reactive protein and the risk of future cardiovascular events among apparently healthy women. Circulation. 1998 Aug 25;98(8):731-3.
8. Ballantyne CM, Hoogeveen RC, Bang H, et al. Lipoprotein-associated phospholipase A2, high-sensitivity C-reactive protein, and risk for incident ischemic stroke in middle-aged men and women in the Atherosclerosis Risk in Communities (ARIC) study. Arch Intern Med. 2005 Nov 28;165(21):2479-84.
9. Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008 Nov 20;359(21):2195-207.
10. Anty R, Bekri S, Luciani N, et al. The inflammatory C-reactive protein is increased in both liver and adipose tissue in severely obese patients independently from metabolic syndrome, Type 2 diabetes, and NASH. Am J Gastroenterol. 2006 Aug;101(8):1824-33.
11. Available at: http://www.medscape.com/viewarticle/513056. Accessed February 19, 2009.
12. Available at: http://www.lifeextension.com/protocols/appendix/blood_testing_02.htm. Accessed February 19, 2009.
13. Visser M, Bouter LM, McQuillan GM, Wener MH, Harris TB. Elevated C-reactive protein levels in overweight and obese adults. JAMA. 1999 Dec 8;282(22):2131-5.
14. Block G, Jensen CD, Dalvi TB, et al. Vitamin C treatment reduces elevated C-reactive protein. Free Radic Biol Med. 2009 Jan 1;46(1):70-7.
15. Available at: http://berkeley.edu/news/media/releases/2008/11/12_vitaminc.shtml. Accessed February 19, 2009.
16. Baillargeon J, Rose DP. Obesity, adipokines, and prostate cancer (review). Int J Oncol. 2006 Mar;28(3):737-45.
17. Abu-Abid S, Szold A, Klausner J. Obesity and cancer. J Med. 2002;33(1-4):73-86.
18. Morimoto LM, White E, Chen Z, et al. Obesity, body size, and risk of postmenopausal breast cancer: the Women’s Health Initiative (United States). Cancer Causes Control. 2002 Oct;13(8):741-51.
19. Bonora E. The metabolic syndrome and cardiovascular disease. Ann Med. 2006;38(1):64-80.
20. Ridker PM. Inflammatory biomarkers and risks of myocardial infarction, stroke, diabetes, and total mortality: implications for longevity. Nutr Rev. 2007 Dec;65(12 Pt 2):S253-9.
21. Haffner SM. Abdominal adiposity and cardiometabolic risk: do we have all the answers? Am J Med. 2007 Sep;120(9 Suppl 1):S10-6.
22. Semiz S, Rota S, Ozdemir O, Ozdemir A, Kaptanoglu B. Are C-reactive protein and hom*ocysteine cardiovascular risk factors in obese children and adolescents? Pediatr Int. 2008 Aug;50(4):419-23.
23. Haffner SM. Relationship of metabolic risk factors and development of cardiovascular disease and diabetes. Obesity (Silver Spring). 2006 Jun;14(Suppl 3):121S-S.
24. Whitmer RA. The epidemiology of adiposity and dementia. Curr Alzheimer Res. 2007 Apr;4(2):117-22.
25. Petersson H, Lind L, Hulthe J, Elmgren A, Cederholm T, Riserus U. Relationships between serum fatty acid composition and multiple markers of inflammation and endothelial function in an elderly population. Atherosclerosis. 2008 Jul 1.
26. Levitan EB, Cook NR, Stampfer MJ, et al. Dietary glycemic index, dietary glycemic load, blood lipids, and C-reactive protein. Metabolism. 2008 Mar;57(3):437-43.
27. Pirro M, Schillaci G, Savarese G, et al. Attenuation of inflammation with short-term dietary intervention is associated with a reduction of arterial stiffness in subjects with hypercholesterolaemia. Eur J Cardiovasc Prev Rehabil. 2004 Dec;11(6):497-502.
28. Jenkins DJ, Kendall CW, Marchie A, et al. Effects of a dietary portfolio of cholesterol-lowering foods vs lovastatin on serum lipids and C-reactive protein. JAMA. 2003 Jul 23;290(4):502-10.
29. Ajani UA, Ford ES, Mokdad AH. Dietary fiber and C-reactive protein: findings from national health and nutrition examination survey data. J Nutr. 2004 May;134(5):1181-5.
30. Tang YJ, Lee WJ, Chen YT, et al. Serum testosterone level and related metabolic factors in men over 70 years old. J Endocrinol Invest. 2007 Jun;30(6):451-8.
31. Nakhai Pour HR, Grobbee DE, Muller M, Van der Schouw YT. Association of endogenous sex hormone with C-reactive protein levels in middle-aged and elderly men. Clin Endocrinol (Oxf). 2007 Mar;66(3):394-8.
32. Choi BG, McLaughlin MA. Why men’s hearts break: cardiovascular effects of sex steroids. Endocrinol Metab Clin North Am. 2007 Jun;36(2):365-77.
33. Chainani-Wu N. Safety and anti-inflammatory activity of curcumin: a component of turmeric (Curcuma longa). J Altern Complement Med. 2003 Feb;9(1):161-8.
34. Zhang F, Altorki NK, Mestre JR, Subbaramaiah K, Dannenberg AJ. Curcumin inhibits cyclooxygenase-2 transcription in bile acid- and phorbol ester-treated human gastrointestinal epithelial cells. Carcinogenesis. 1999 Mar;20(3):445-51.
35. Satoskar RR, Shah SJ, Shenoy SG. Evaluation of anti-inflammatory property of curcumin (diferuloyl methane) in patients with postoperative inflammation. Int J Clin Pharmacol Ther Toxicol. 1986 Dec;24(12):651-4.
36. Ramsewak RS, DeWitt DL, Nair MG. Cytotoxicity, antioxidant and anti-inflammatory activities of curcumins I-III from Curcuma longa. Phytomedicine. 2000 Jul;7(4):303-8.
37. Pendurthi UR, Williams JT, Rao LV. Inhibition of tissue factor gene activation in cultured endothelial cells by curcumin. Suppression of activation of transcription factors Egr-1, AP-1, and NF-kappa B. Arterioscler Thromb Vasc Biol. 1997 Dec;17(12):3406-13.
38. Oben JE, Ngondi JL, Blum K. Inhibition of Irvingia gabonensis seed extract (OB131) on adipogenesis as mediated via down regulation of the PPARgamma and Leptin genes and up-regulation of the adiponectin gene. Lipids Health Dis. 2008;744.
39. Available at: http://stanford.wellsphere.com/healthy-eating-article/more-information-on-irvingia/544189. Accessed Feb 12, 2009.
40. Ngondi JL, Oben JE, Minka SR. The effect of Irvingia gabonensis seeds on body weight and blood lipids of obese subjects in Cameroon. Lipids Health Dis. 2005 May 25;412.
41. Shea MK, Booth SL, Massaro JM, et al. Vitamin K and vitamin D status: associations with inflammatory markers in the Framingham Offspring Study. Am J Epidemiol. 2008 Feb 1;167(3):313-20.
42. Reddi K, Henderson B, Meghji S, et al. Interleukin 6 production by lipopolysaccharide-stimulated human fibroblasts is potently inhibited by naphthoquinone (vitamin K) compounds. Cytokine. 1995 Apr;7(3):287-90.
43. Ozaki I, Zhang H, Mizuta T, et al. Menatetrenone, a vitamin K2 analogue, inhibits hepatocellular carcinoma cell growth by suppressing cyclin D1 expression through inhibition of nuclear factor kappaB activation. Clin Cancer Res. 2007 Apr 1;13(7):2236-45.
44. Ueda H, Yamazaki C, Yamazaki M. Luteolin as an anti-inflammatory and anti-allergic constituent of Perilla frutescens. Biol Pharm Bull. 2002 Sep;25(9):1197-202.
45. Das M, Ram A, Ghosh B. Luteolin alleviates bronchoconstriction and airway hyperreactivity in ovalbumin sensitized mice. Inflamm Res. 2003 Mar;52(3):101-6.
46. Xagorari A, Papapetropoulos A, Mauromatis A, et al. Luteolin inhibits an endotoxin-stimulated phosphorylation cascade and proinflammatory cytokine production in macrophages. J Pharmacol Exp Ther. 2001 Jan;296(1):181-7.
47. Wu D, Han SN, Meydani M, Meydani SN. Effect of concomitant consumption of fish oil and vitamin E on production of inflammatory cytokines in healthy elderly humans. Ann NY Acad Sci. 2004 Dec;1031:422-4.
48. Lo CJ, Chiu KC, Fu M, Lo R, Helton S. Fish oil decreases macrophage tumor necrosis factor gene transcription by altering the NF kappa B activity. J Surg Res. 1999 Apr;82(2):216-21.
49. Caughey GE, Mantzioris E, Gibson RA, Cleland LG, James MJ. The effect on human tumor necrosis factor alpha and interleukin 1 beta production of diets enriched in n-3 fatty acids from vegetable oil or fish oil. Am J Clin Nutr. 1996 Jan;63(1):116-22.
50. Kremer JM. n-3 fatty acid supplements in rheumatoid arthritis. Am J Clin Nutr. 2000 Jan;71(1 Suppl):349S-51S.
51. Jolly CA, Muthukumar A, Avula CP, Troyer D, Fernandes G. Life span is prolonged in food-restricted autoimmune-prone (NZB x NZW)F(1) mice fed a diet enriched with (n-3) fatty acids. J Nutr. 2001 Oct;131(10):2753-60.
52. Pischon T, Hankinson SE, Hotamisligil GS, et al. Habitual dietary intake of n-3 and n-6 fatty acids in relation to inflammatory markers among US men and women. Circulation. 2003 Jul 15;108(2):155-60.
53. Madsen T, Skou HA, Hansen VE, et al. C-reactive protein, dietary n-3 fatty acids, and the extent of coronary artery disease. Am J Cardiol. 2001 Nov 15;88(10):1139-42.
54. Kast RE. Borage oil reduction of rheumatoid arthritis activity may be mediated by increased cAMP that suppresses tumor necrosis factor-alpha. Int Immunopharmacol. 2001 Nov;1(12):2197-9.
55. Rothman D, DeLuca P, Zurier RB. Botanical lipids: effects on inflammation, immune responses, and rheumatoid arthritis. Semin Arthritis Rheum. 1995 Oct;25(2):87-96.
56. Izgut-Uysal VN, Agac A, Derin N. Effect of L-carnitine on carrageenan-induced inflammation in aged rats. Gerontology. 2003 Sep;49(5):287-92.
57. Bellinghieri G, Santoro D, Calvani M, Savica V. Role of carnitine in modulating acute-phase protein synthesis in hemodialysis patients. J Ren Nutr. 2005 Jan;15(1):13-7.
58. Savica V, Calvani M, Benatti P, et al. Carnitine system in uremic patients: molecular and clinical aspects. Semin Nephrol. 2004 Sep;24(5):464-8.
59. Maramag C, Menon M, Balaji KC, Reddy PG, Laxmanan S. Effect of vitamin C on prostate cancer cells in vitro: effect on cell number, viability, and DNA synthesis. Prostate. 1997 Aug 1;32(3):188-95.
60. Calabrese V, Giuffrida Stella AM, Calvani M, Butterfield DA. Acetylcarnitine and cellular stress response: roles in nutritional redox homeostasis and regulation of longevity genes. J Nutr Biochem. 2006 Feb;17(2):73-88.
61. Wei DZ, Yang JY, Liu JW, Tong WY. Inhibition of liver cancer cell proliferation and migration by a combination of (-)-epigallocatechin-3-gallate and ascorbic acid. J Chemother. 2003 Dec;15(6):591-5.
62. Sanchez-Moreno C, Cano MP, de AB, et al. High-pressurized orange juice consumption affects plasma vitamin C, antioxidative status and inflammatory markers in healthy humans. J Nutr. 2003 Jul;133(7):2204-9.
63. Kaul D, Baba MI. Genomic effect of vitamin ‘C’ and statins within human mononuclear cells involved in atherogenic process. Eur J Clin Nutr. 2005 Aug;59(8):978-81.
64. Korantzopoulos P, Kolettis TM, Kountouris E, et al. Oral vitamin C administration reduces early recurrence rates after electrical cardioversion of persistent atrial fibrillation and attenuates associated inflammation. Int J Cardiol. 2005 Jul 10;102(2):321-6.
65. Majewicz J, Rimbach G, Proteggente AR, et al. Dietary vitamin C down-regulates inflammatory gene expression in apoE4 smokers. Biochem Biophys Res Commun. 2005 Dec 16;338(2):951-5.
66. Aneja R, Odoms K, Denenberg AG, Wong HR. Theaflavin, a black tea extract, is a novel anti-inflammatory compound. Crit Care Med. 2004 Oct;32(10):2097-103.
67. Pan MH, Lin-Shiau SY, Ho CT, Lin JH, Lin JK. Suppression of lipopolysaccharide-induced nuclear factor-kappaB activity by theaflavin-3,3’-digallate from black tea and other polyphenols through down-regulation of IkappaB kinase activity in macrophages. Biochem Pharmacol. 2000 Feb 15;59(4):357-67.
68. Liang YC, Tsai DC, Lin-Shiau SY, et al. Inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced inflammatory skin edema and ornithine decarboxylase activity by theaflavin-3,3’-digallate in mouse. Nutr Cancer. 2002;42(2):217-23.
69. Lin JK. Cancer chemoprevention by tea polyphenols through modulating signal transduction pathways. Arch Pharm Res. 2002 Oct;25(5):561-71.
70. Cai F, Li CR, Wu JL, et al. Theaflavin ameliorates cerebral ischemia-reperfusion injury in rats through its anti-inflammatory effect and modulation of STAT-1. Mediators Inflamm. 2006;2006(5):30490.
71. Siddiqui IA, Adhami VM, Afaq F, Ahmad N, Mukhtar H. Modulation of phosphatidylinositol-3-kinase/protein kinase B- and mitogen-activated protein kinase-pathways by tea polyphenols in human prostate cancer cells. J Cell Biochem. 2004 Feb 1;91(2):232-42.
72. Ma Y, Hebert JR, Li W, et al. Association between dietary fiber and markers of systemic inflammation in the Women’s Health Initiative Observational Study. Nutrition. 2008 Oct;24(10):941-9.
73. Jacobs LR. Relationship between dietary fiber and cancer: metabolic, physiologic, and cellular mechanisms. Proc Soc Exp Biol Med. 1986 Dec;183(3):299-310.
74. Galvez J, Rodriguez-Cabezas ME, Zarzuelo A. Effects of dietary fiber on inflammatory bowel disease. Mol Nutr Food Res. 2005 Jun;49(6):601-8.
75. Qi L, van Dam RM, Liu S, et al. Whole-grain, bran, and cereal fiber intakes and markers of systemic inflammation in diabetic women. Diabetes Care. 2006 Feb;29(2):207-11.
76. Wang XL, Rainwater DL, Mahaney MC, Stocker R. Cosupplementation with vitamin E and coenzyme Q10 reduces circulating markers of inflammation in baboons. Am J Clin Nutr. 2004 Sep;80(3):649-55.
77. Kunitomo M, Yamaguchi Y, Kagota S, Otsubo K. Beneficial effect of coenzyme Q10 on increased oxidative and nitrative stress and inflammation and individual metabolic components developing in a rat model of metabolic syndrome. J Pharmacol Sci. 2008 Jun;107(2):128-37.
78. Chan YH, Lau KK, Yiu KH, et al. Reduction of C-reactive protein with isoflavone supplement reverses endothelial dysfunction in patients with ischaemic stroke. Eur Heart J. 2008 Nov;29(22):2800-7.
79. Joyal S. Guard your precious proteins against premature aging. Life Extension. 2008 Apr;14(3):37-43.
80. Vlassara H, Cai W, Crandall J, et al. Inflammatory mediators are induced by dietary glycotoxins, a major risk factor for diabetic angiopathy. Proc Natl Acad Sci USA. 2002 Nov 26;99(24):15596-601.
81. Dyer DG, Blackledge JA, Katz BM, et al. The Maillard reaction in vivo. Z Ernahrungswiss. 1991 Feb;30(1):29-45.
82. Baynes JW, Thorpe SR. Glycoxidation and lipoxidation in atherogenesis. Free Radic Biol Med. 2000 Jun 15;28(12):1708-16.
83. Mustapha IZ, Debrey S, Oladubu M, Ugarte R. Markers of systemic bacterial exposure in periodontal disease and cardiovascular disease risk: a systematic review and meta-analysis. J Periodontol. 2007 Dec;78(12):2289-302.
84. Moutsopoulos NM, Madianos PN. Low-grade inflammation in chronic infectious diseases: paradigm of periodontal infections. Ann NY Acad Sci. 2006 Nov;1088:251-64.
85. Loos BG, Craandijk J, Hoek FJ, Wertheim-van Dillen PM, Van Der Velden U., Elevation of systemic markers related to cardiovascular diseases in the peripheral blood of periodontitis patients. J Periodontol. 2000 Oct;71(10):1528-34.
86. Wu T, Trevisan M, Genco RJ, et al. Examination of the relation between periodontal health status and cardiovascular risk factors: serum total and high density lipoprotein cholesterol, C-reactive protein, and plasma fibrinogen. Am J Epidemiol. 2000 Feb 1;151(3):273-82.
87. Abou-Raya S, Bou-Raya A, Naim A, Abuelkheir H. Rheumatoid arthritis, periodontal disease and coronary artery disease. Clin Rheumatol. 2008 Apr;27(4):421-7.
88. Paquette DW. The periodontal-cardiovascular link. Compend Contin Educ Dent. 2004 Sep;25(9):681-92.
89. Chiu HM, Lin JT, Chen TH, et al. Elevation of C-reactive protein level is associated with synchronous and advanced colorectal neoplasm in men. Am J Gastroenterol. 2008 Sep;103(9):2317-25.
90. Groblewska M, Mroczko B, Wereszczynska-Siemiatkowska U, et al. Serum interleukin 6 (IL-6) and C-reactive protein (CRP) levels in colorectal adenoma and cancer patients. Clin Chem Lab Med. 2008;46(10):1423-8.
91. Caruso C, Lio D, Cavallone L, Franceschi C. Aging, longevity, inflammation, and cancer. Ann NY Acad Sci. 2004 Dec;1028:1-13.
92. Paganelli R, Di IA, Patricelli L, et al. Proinflammatory cytokines in sera of elderly patients with dementia: levels in vascular injury are higher than those of mild-moderate Alzheimer’s disease patients. Exp Gerontol. 2002 Jan;37(2-3):257-63.
93. Zuliani G, Ranzini M, Guerra G, et al. Plasma cytokines profile in older subjects with late onset Alzheimer’s disease or vascular dementia. J Psychiatr Res. 2007 Oct;41(8):686-93.
94. Yaffe K, Kanaya A, Lindquist K, et al. The metabolic syndrome, inflammation, and risk of cognitive decline. JAMA. 2004 Nov 10;292(18):2237-42.
95. Di Napoli M, Papa F, Bocola V. C-reactive protein in ischemic stroke: an independent prognostic factor. Stroke. 2001 Apr;32(4):917-24.
96. Shantikumar S, Grant PJ, Catto AJ, Bamford JM, Carter AM. Elevated C-Reactive Protein and Long-Term Mortality After Ischaemic Stroke. Relationship With Markers of Endothelial Cell and Platelet Activation. Stroke. 2009 Jan 22.
97. Sabatine MS, Morrow DA, Jablonski KA, et al. Prognostic significance of the Centers for Disease Control/American Heart Association high-sensitivity C-reactive protein cut points for cardiovascular and other outcomes in patients with stable coronary artery disease. Circulation. 2007 Mar 27;115(12):1528-36.
98. Boekhoorn SS, Vingerling JR, Witteman JC, Hofman A, de Jong PT. C-reactive protein level and risk of aging macula disorder: The Rotterdam Study. Arch Ophthalmol. 2007 Oct;125(10):1396-401.
99. Seddon JM, Gensler G, Milton RC, Klein ML, Rifai N. Association between C-reactive protein and age-related macular degeneration. JAMA. 2004 Feb 11;291(6):704-10.
100. Joosten LA, Netea MG, Kim SH, et al. IL-32, a proinflammatory cytokine in rheumatoid arthritis. Proc Natl Acad Sci USA. 2006 Feb 28;103(9):3298-303.
101. Mosaad YM, Metwally SS, Auf FA, et al. Proinflammatory cytokines (IL-12 and IL-18) in immune rheumatic diseases: relation with disease activity and autoantibodies production. Egypt J Immunol. 2003;10(2):19-26.
102. Kiecolt-Glaser JK, Preacher KJ, MacCallum RC, et al. Chronic stress and age-related increases in the proinflammatory cytokine IL-6. Proc Natl Acad Sci USA. 2003 Jul 22;100(15):9090-5.
103. Antoniades CG, Berry PA, Wendon JA, Vergani D. The importance of immune dysfunction in determining outcome in acute liver failure. J Hepatol. 2008 Nov;49(5):845-61.
104. Mani AR, Montagnese S, Jackson CD, et al. Decreased heart rate variability in patients with cirrhosis relates to the presence and degree of hepatic encephalopathy. Am J Physiol Gastrointest Liver Physiol. 2009 Feb;296(2):G330-8.
105. Jialal I, Devaraj S. Inflammation and atherosclerosis: the value of the high-sensitivity C-reactive protein assay as a risk marker. Am J Clin Pathol. 2001 Dec;116(Suppl):S108-15.
106. Kuch B, von Scheidt W, Kling B, et al. Differential impact of admission C-reactive protein levels on 28-day mortality risk in patients with ST-elevation versus non-ST-elevation myocardial infarction (from the Monitoring Trends and Determinants on Cardiovascular Diseases [MONICA]/Cooperative Health Research in the Region of Augsburg [KORA] Augsburg Myocardial Infarction Registry). Am J Cardiol. 2008 Nov 1;102(9):1125-30.
107. Jeppesen J, Hansen TW, Olsen MH, et al. C-reactive protein, insulin resistance and risk of cardiovascular disease: a population-based study. Eur J Cardiovasc Prev Rehabil. 2008 Oct;15(5):594-8.
108. Mach F. Inflammation is a crucial feature of atherosclerosis and a potential target to reduce cardiovascular events. Handb Exp Pharmacol. 2005;(170):697-722.
109. Kanda T. C-reactive protein (CRP) in the cardiovascular system. Rinsho Byori. 2001 Apr;49(4):395-401.
110. McMillan DC, Leen E, Smith J, et al. Effect of extended ibuprofen administration on the acute phase protein response in colorectal cancer patients. Eur J Surg Oncol. 1995 Oct;21(5):531-4.
111. Ikonomidis I, Andreotti F, Economou E, et al. Increased proinflammatory cytokines in patients with chronic stable angina and their reduction by aspirin. Circulation. 1999 Aug 24;100(8):793-8.
112. Arena R, Arrowood JA, Fei DY, Helm S, Kraft KA. The relationship between C-reactive protein and other cardiovascular risk factors in men and women. J Cardiopulm Rehabil. 2006 Sep-Oct;26(5):323-7; quiz 328-9.
113. Sampietro T, Bigazzi F, Dal PB, et al. Increased plasma C-reactive protein in familial hypoalphalipoproteinemia: a proinflammatory condition? Circulation. 2002 Jan 1;105(1):11-4.
114. Malkin CJ, Pugh PJ, Jones RD, Jones TH, Channer KS. Testosterone as a protective factor against atherosclerosis--immunomodulation and influence upon plaque development and stability. J Endocrinol. 2003 Sep;178(3):373-80.
115. Nakhai Pour HR, Grobbee DE, Muller M, van der Schouw YT. Association of endogenous sex hormone with C-reactive protein levels in middle-aged and elderly men. Clin Endocrinol (Oxf). 2007 Mar;66(3):394-8.
116. Shankar A, Li J. Positive association between high-sensitivity C-reactive protein level and diabetes mellitus among US non-Hispanic black adults. Exp Clin Endocrinol Diabetes. 2008 Aug;116(8):455-60.
117. Aronson D, Avizohar O, Levy Y, Bartha P, Jacob G, Markiewicz W. Factor analysis of risk variables associated with low-grade inflammation. Atherosclerosis. 2008 Sep;200(1):206-12.
118. Holven KB, Aukrust P, Retterstol K, et al. Increased levels of C-reactive protein and interleukin-6 in hyperhom*ocysteinemic subjects. Scand J Clin Lab Invest. 2006;66(1):45-54.
119. Tengstrand B, Carlstrom K, Fellander-Tsai L, Hafstrom I. Abnormal levels of serum dehydroepiandrosterone, estrone, and estradiol in men with rheumatoid arthritis: high correlation between serum estradiol and current degree of inflammation. J Rheumatol. 2003 Nov;30(11):2338-43.
120. Rifai N, Ridker PM. Inflammatory markers and coronary heart disease. Curr Opin Lipidol. 2002 Aug;13(4):383-9.
121. Albert CM, Ma J, Rifai N, Stampfer MJ, Ridker PM. Prospective study of C-reactive protein, hom*ocysteine, and plasma lipid levels as predictors of sudden cardiac death. Circulation. 2002 Jun 4;105(22):2595-9.
122. Bermudez EA, Ridker PM. C-reactive protein, statins, and the primary prevention of atherosclerotic cardiovascular disease. Prev Cardiol. 2002;5(1):42-6.
123. Willerson JT, Ridker PM. Inflammation as a cardiovascular risk factor. Circulation. 2004 Jun 1;109(21 Suppl 1):II2-10.
124. Di Napoli M, Papa F, Bocola V. Prognostic influence of increased C-reactive protein and fibrinogen levels in ischemic stroke. Stroke. 2001 Jan;32(1):133-8.
125. Nilsson K, Gustafson L, Hultberg B. C-reactive protein: vascular risk marker in elderly patients with mental illness. Dement Geriatr Cogn Disord. 2008;26(3):251-6.
126. Komulainen P, Lakka TA, Kivipelto M, et al. Serum high sensitivity C-reactive protein and cognitive function in elderly women. Age Ageing. 2007 Jul;36(4):443-8.
127. Maugeri D, Russo MS, Franze C, et al. Correlations between C-reactive protein, interleukin-6, tumor necrosis factor-alpha and body mass index during senile osteoporosis. Arch Gerontol Geriatr. 1998 Sep;27(2):159-63.
128. Teoh H, Quan A, Lovren F, et al. Impaired endothelial function in C-reactive protein overexpressing mice. Atherosclerosis. 2008 Dec;201(2):318-25.
129. Singh U, Devaraj S, Vasquez-Vivar J, Jialal I. C-reactive protein decreases endothelial nitric oxide synthase activity via uncoupling. J Mol Cell Cardiol. 2007 Dec;43(6):780-91.
130. Bisoendial RJ, Kastelein JJ, Stroes ES. C-reactive protein and atherogenesis: from fatty streak to clinical event. Atherosclerosis. 2007 Dec;195(2):e10-8.
131. Schwedler SB, Kuhlencordt PJ, Ponnuswamy PP, et al. Native C-reactive protein induces endothelial dysfunction in ApoE-/- mice: implications for iNOS and reactive oxygen species. Atherosclerosis. 2007 Dec;195(2):e76-84.
132. Ferri C, Croce G, Cofini V, et al. C-reactive protein: interaction with the vascular endothelium and possible role in human atherosclerosis. Curr Pharm Des. 2007;13(16):1631-45.
133. Ebbing M, Bleie O, Ueland PM, et al. Mortality and cardiovascular events in patients treated with hom*ocysteine-lowering B vitamins after coronary angiography: a randomized controlled trial. JAMA. 2008 Aug 20;300(7):795-804.
134. Jarosz A, Nowicka G. C-reactive protein and hom*ocysteine as risk factors of atherosclerosis. Przegl Lek. 2008;65(6):268-72.