Looking for a readily available, safe, and inexpensive way to reduce C-reactive protein in patients at increased risk for cardiovascular disease? Consider multivitamins.
C-reactive protein (CRP) became front-page news last month when two studies in the New England Journal of Medicine showed that statin-induced reductions in CRP could reduce risk of cardiovascular events. Almost overnight, this marker of inflammation—long recognized by some cardiovascular researchers as a key risk factor—became the center of a media blizzard, and untold numbers of people suddenly had a new number to worry about. The news reports raised a critical clinical question: what to do when CRP is high?
But absent from almost all major news coverage was a study published in 2003 showing that a multivitamin could reduce CRP by over 30% in patients at increased risk for heart disease. Add that to other studies showing that smoking cessation, low-fat plant-based diets and exercise are linked to lower CRP levels, and it seems that an effective holistic strategy to attenuate this risk factor is much closer at hand than most physicians realize.
“For some reason, all of the reports covering the recent studies failed to talk about nutrition and supplements. Well over a year ago, we published data showing that a multivitamin could reduce CRP by as much as 32%,” said Timothy Church, MD, MPH, PhD, medical director of the Cooper Institute, a non-profit nutrition and exercise research center founded in Dallas by Kenneth Cooper, MD, a pioneer in the field of nutrition and aerobic exercise.
Nutrition & CRP
Dr. Cooper’s “Cooper Complete” multivitamin, which is commercially available, is designed to reduce cardiovascular risk. It is comprised of 24 component nutrients, and with the exception of coenzyme Q10, lutein and lycopene, most are standard ingredients in multivitamin products.
Back in 2001, Dr. Church and his colleagues were studying the effects of the formula on lipid profiles and homocysteine in a cohort of men and women at moderately increased risk of CVD and diabetes. The patients were randomized to 6 months of daily supplementation with Cooper Complete or a placebo. An early believer in CRP as a risk predictor, Dr. Church routinely measured baseline CRP levels, though the study was not originally designed to look at CRP. Fortunately, he kept frozen blood samples for most of the subjects.
When several smaller, uncontrolled studies suggested that vitamin E (d-α-tocopherol), and vitamin B6 were inversely associated with CRP levels, Dr. Church went back to the frozen samples to see if the Cooper Complete formula had any effect on CRP.
Because CRP can fluctuate by as much as 44% over the course of a woman’s menstrual cycle, Dr. Church opted to analyze data only from males and post-menopausal women. They looked at blood from 44 patients on placebo and 43 on the multivitamin; 85% of the subjects were White, with the remainder being African American (9%) and Hispanic (6%). Baseline body mass indices were 27.5 in the placebo group and 26.9 in the multivitamin group. Mean total cholesterols were 207.8 mg/dl and 208 mg/dl, respectively, and mean baseline CRPs were 2.44 mg/L and 2.19 mg/L, respectively. In all, this was a fairly garden-variety moderate-to-high risk population.
Thirty percent of those in the multivitamin group and 27% of those on placebo had “high risk” baseline CRPs, defined as 3 mg/L or greater. This is in accord with the American Heart Association’s current CRP guidelines.
Higher Risk, Bigger Benefit
Blood samples taken at the end of the 6-month trial showed that only 14% of those in the multivitamin group had CRPs greater than 3, a nearly 50% decrease. In contrast, 32% of those in the placebo group had CRPs above 3. The subjects on the multivitamin had a median decline of CRP of 0.7 mg/L, compared with a median increase of 0.2 in the placebo group. Interestingly, those subjects with the highest baseline CRPs, which in some cases exceeded 9 mg/L, also had the greatest vitamin-associated reductions, typically on the order of an 8 mg/L drop (Church TS, et al. Am J Med. 2003; 115:702–07).
In an effort to better understand how vitamins affect CRP, Dr. Church studied correlations between CRP and serum levels of 6 of the 24 nutrients in the Cooper Complete formula. Though it was largely a vitamin E study that prompted him to look at CRP in the first place, he found no vitamin E effect in this population.
“Vitamin B6 and vitamin C were the big players,” he told Holistic Primary Care in an interview. “They showed the strongest correlations, but in truth we really don’t know if it is these specific components or a synergy between the different ingredients.” In a sense, it is beside the point. “The whole idea of a multivitamin is it provides nutrients in combinations and proportions that are closer to normal physiology and the nutrition we get from whole foods. You don’t go to a vitamin C tree and pick a vitamin C fruit. You eat an orange and you get vitamin C with lots of other nutrients.
Though his study was done with a specific formula developed by Dr. Cooper, Dr. Church said one could expect similar CRP reductions with consistent use of “other similarly formulated multivitamins.”
Overcoming Resistance to CRP Assessment
The medical community has been slow to embrace CRP measurement for routine assessment of CVD risk. Dr. Church attributed the reluctance to several factors. For one, CRP tends to fluctuate independent of lipid profiles and thus represents a departure from the lipid-oriented thinking that has dominated the conventional approach to CVD risk reduction.
Secondly, CRP is a non-specific and highly volatile indicator of inflammation. “It is an acute phase reactant. Almost anything can blow CRP through the roof. If you have an infection, an impacted tooth, a traumatic knee injury, intense emotional stress, you’ll see rapid increases in CRP. A person’s cholesterol level doesn’t go from 100 to 200 in days or even months. But CRP can go from 0.5 to 28 overnight, and it is even more subject to variation than blood pressure. It is kind of like a smoke alarm. So, you really have to look at everything that’s going on with the patient to see whether there really is a fire or not.”
From a heart health viewpoint, sudden surges in CRP are not as worrisome as steady rises. “It is the people who are consistently up over 3 mg/L on multiple repeated measurements that get me really nervous,” Dr. Church said.
The third reason is that most conventionally trained physicians have not known how to respond therapeutically to an elevated CRP level. “If there had been a drug to treat CRP, it would have been a household word 10 years ago.”
Vitamins Versus Statins
Dr. Church believes CRP measurement should be routine for patients with significant CVD risk profiles, and he predicted that mainstream medicine will rapidly move in this direction in light of the Nissen and Ridker studies (Nissen SE, et al. N Engl J Med. 2005; 352(1):29–38 and Ridker PM, et al. N Engl J Med. 2005; 352(1): 20–28) published last month. He applauded the trials, noting that, “Those two studies have basically guaranteed CRP a future.”
Both studies, however, assessed the effects of statin drugs (pravastatin and atorvastatin) in patients who already had advanced CVD. The Ridker trial was in post-infarction patients. While the data showed statins can reduce CRP on a population basis, and the effect is independent of the lipid-lowering effect, CRP response to statins is highly variable from person to person. There is little information on whether these drugs work to lower CRP in patients with earlier stage disease.
According to Dr. Church, statins are a suboptimal answer to the CRP challenge. “We’re putting people on statins, and also telling them to exercise more. The problem is, statins can do very weird things to muscle [See Holistic Primary Care Oct. 15, 2002: “Petition Urges FDA to Mandate CoQ10 Recommendation on Statin Labels”]. I have so many patients on statins who tell me that they get unbearably sore after they run.” Among a number of studies ongoing at the Cooper Institute is a trial looking at the impact of statin drugs on muscle health and exercise capacity.
Dr. Church also has two National Institutes of Health grants to study the impact of exercise on CRP, independent of any pharmacologic or nutraceuticals intervention. “Cross-sectionally, we know that physically active people have much lower CRPs than people who are totally inactive. But we don’t yet know whether change in activity level will result in change in CRP.”
There are, indeed, many questions about CRP that remain to be answered by future trials. There is provocative preliminary research suggesting that diet and lifestyle changes, particularly a shift toward the Mediterranean approach, can lower CRP, and there may be many different nutrients that can be of benefit. “In terms of our current understanding CRP, we are where we were with cholesterol 30 or 40 years ago.”
To learn more about the Cooper Complete vitamin formula, visit www.coopercomplete.com.
