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EDITORIAL
Hans Larsen, Editor |
LETTERS TO THE EDITOR
I just want to simply say that the information given on the prevention of prostate cancer on your web site was
indeed helpful. I find that I am now more educated on this all-important issue.
JBS, USA
Editor: For anyone else interested in this topic you can find the information at www.yourhealthbase.com/prostate_cancer.html
I am a 58-year-old aerobic instructor. I look like I'm 45 and feel like I'm 35. I started vitamin B-12 injections 3 months ago and they really make me feel good. My question is how long can a person take the injection? I am taking one every 6 weeks. SJL, USA Editor: I am assuming your injections are 1 mg (1000 micrograms). If so, I am not aware of any reason why you could not continue indefinitely having an injection every 6 weeks. You may be able to achieve the same result by daily oral supplementation (sublingual) with 1 mg of vitamin B-12. My husband and I have been trying to get pregnant for a year now. I started taking folic acid then. I take one a day and was wondering if this is good for me or am I taking too much? AM, UK Editor: A daily intake of folic acid of up to 1000 micrograms (1 mg) is safe. There is some indication that it can help achieve pregnancy, but it should be taken by both you and your husband. Dutch researchers have found that men who supplement with zinc and folic acid increase their sperm count by 74%. My son of 39 years had a blood clot 2 months ago and the doctor has put him on Coumadin. Would fish oil be good for him to take and would it interaction with the Coumadin? I am hoping he can get off the Coumadin. VF, USA Editor: Fish oils do not change the effect of Coumadin (warfarin) and there is no evidence that they increase bleeding tendency[1]. [1] Eritsland, J, et al. Long-term effects of n-3 polyunsaturated fatty acids on haemostatic variables and bleeding episodes in patients with coronary artery disease. Blood Coagulation and Fibrinolysis, Vol. 6, 1995, pp. 17-22
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ABSTRACTS
VITAMIN D HELPS PREVENT HIP FRACTURES
BOSTON, MASSACHUSETTS. Hip fractures caused by osteoporosis are a serious problem especially
among postmenopausal women. Conventional wisdom has it that a high daily intake of milk and/or calcium
from food and supplements will go a long way towards avoiding such fractures. Several trials of calcium
supplementation have indeed shown that a high calcium intake increases bone density, but longer term
studies have not found that this translates into a reduced risk of hip fractures. It is also clear that any
possible benefits of calcium supplementation are reversed fairly quickly if supplementation is
discontinued.
SKIN HEALTH AND NUTRITION
ZEIST, THE NETHERLANDS. A healthy skin begins from the inside, but little information is available as to
how nutrition actually affects skin health and appearance. A group of Dutch researchers has now taken a
preliminary step towards discovering the relationship between diet and skin health. Their study involved 149
men (aged 19-73 years) and 153 women (aged 18-73 years). All participants completed food frequency
questionnaires and had blood samples drawn for analysis of vitamin A (retinol), vitamin E (alpha-tocopherol),
vitamin C (ascorbic acid), beta-carotene, lycopene, lutein, zeaxanthin, and beta-cryptoxanthin.
LYCOPENE HELPS PREVENT ATHEROSCLEROSIS
KUOPIO, FINLAND. Several studies have concluded that high blood levels of lycopene (a cousin of beta-
carotene) are associated with a reduced risk of cardiovascular disease. Researchers at the University of
Kuopio have just completed a study to determine if lycopene works by preventing or slowing down the
progression of atherosclerosis, the forerunner of cardiovascular disease. Atherosclerosis involves a
thickening of the inner wall (intima) of the arteries. It is thus possible to follow the progression of
atherosclerosis by a non-invasive, ultrasonic measurement of the intima-media thickness (IMT) of the carotid
arteries.
IS FAST FOOD ADDICTIVE?
WASHINGTON, DC. Obesity and diabetes are growing at alarming rates in countries where fast foods have
become the staple diet. The health commissioner in New York City recently announced that the incidence of
type 2 diabetes in that city now stands at 8% or double the rate encountered in 1994. A growing body of
evidence points to the fast food industry as the main culprit in this disastrous trend. There is now evidence
that meals loaded with fat and sugar not only block the hormonal controls that tell people when they have
eaten enough, but actually act on the brain in much the same way that heroin and nicotine do. Says John
Banzhaf, a Washington law professor, "We might even discover that it is possible to become addicted to the
all-American meal of burgers and fries".
ADA FIGHTING THE MERCURY BATTLE
GAITHERSBURG, MARYLAND. The American Dental Association (ADA) has launched an advertising
campaign to discourage patients from having their amalgam (silver) fillings removed. Many patients and
sometimes even their physicians believe that mercury, the main component of amalgams, plays a role in
promoting such varied diseases as Alzheimer's, multiple sclerosis, and autism. The ADA says the evidence
is not there and their Code of Ethics forbids dentists from advising their patients that there could be a link.
Scientists at the University of Milan disagree with the ADA and point out that several studies have confirmed
that mercury from amalgam dental fillings does enter tissues and that the mercury content of brain, thyroid,
kidney, and pituitary gland tissue is proportional to the number of amalgam fillings. They conclude that the
health effects of amalgam fillings are not at all clear and need further investigation. German researchers
point out that some of the composite materials used in the replacement of amalgam fillings may in
themselves be toxic.
GLUCOSAMINE SULFATE WORKS FOR OSTEOARTHRITIS
PRAGUE, CZECH REPUBLIC. It is estimated that 5-15% of people in the Western world between the ages
of 35 and 74 years suffer from osteoarthritis of the knee. The disease can be quite disabling and there are
no conventional pharmaceutical drugs that prevent its progression. As a matter of fact, there is growing
evidence that the nonsteroidal anti-inflammatory drugs and cox-2 inhibitors commonly used to dull the pain
accompanying the disorder actually accelerate its progression.
FISH PREVENTS STROKE
BOSTON, MASSACHUSETTS. Several studies have shown that regular fish consumption helps protect
against stroke. It is not clear, however, whether fish consumption protects against both ischemic stroke
(stroke caused by a blood clot) and hemorrhagic stroke (stroke caused by a burst blood vessel).
Researchers at the Harvard School of Public Health have now released the results of a major study
designed to answer this question.
OLDER PEOPLE BENEFIT FROM FISH OILS
SEATTLE, WASHINGTON. There is abundant evidence that a diet rich in fatty fish is highly protective
against death from heart disease in people 65 years of age and younger. Now researchers at the University
of Washington and the Fred Hutchinson Cancer Research Center have extended the evidence to include
people with an average age of 78 years. Their study included 54 men and women who had suffered a fatal
heart attack or other fatal ischemic heart disease event, 125 people who had suffered a non-fatal heart
attack, and 179 matched controls. All study subjects had blood samples drawn about 2 years prior to the
cardiovascular event. The phospholipid phase of the blood plasma was isolated and analyzed for its
contents of the fatty acids eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), alpha-linolenic acid
(ALA), and linoleic acid (LA). EPA and DHA are the main constituents of fish oil, ALA is found in canola, flax
and soybean oils, and LA is a main constituent of safflower and cottonseed oils.
METABOLIC SYNDROME AND STRESS
LONDON, UNITED KINGDOM. The incidence of metabolic syndrome (syndrome X, insulin resistance
syndrome) is growing rapidly in the Western world. The syndrome is increasingly viewed as an important
precursor of atherosclerosis and coronary disease. The syndrome consists of a cluster of common
symptoms including insulin resistance, abdominal obesity, hypertension (high blood pressure), high
triglyceride levels, and low levels of "good" cholesterol (HDL cholesterol).
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NEWSBRIEFS
More perils of flying
Simple test for heart disease
Small forests worse than no forests?
Longer life for apples
Pregnant? Go easy on the licorice
Poor health begins in childhood
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RESEARCH REPORT
*******ERRATUM*******
High-Sensitivity C-Reactive Protein & Cardiovascular DiseasePart II
by William R. Ware, Ph.D.Emeritus Professor of Chemistry, University of Western OntarioCRP AS A SCREENING TEST FOR CVD The ideal screening test consists of results giving two non-overlapping distributions of the measured value of the diagnostic, with one distribution for those who are disease free, and the other for those with the disease [20]. Distribution overlap produces false positives and false negatives. In the case of CRP it does not appear to have meaning to view the test in this fashion, since the CRP distribution, expressed in quartiles or quintiles, which is being proposed for assessing risk [4,19] is simply a single, smooth distribution. By the same token, one can question the use of the terms normal, healthy, and disease free (in the context of cardiovascular disease) to describe the subjects who generated baseline CRP distributions quoted in the literature. To take an extreme view, one could argue that while there were no observable indications of disease, a significant fraction of the whole "normal" group (presumably quartiles 2 to 5) carried an elevated future risk factor for CVD, independent of their blood lipid profile, and were thus not necessarily disease free. One could also imagine the possibility that this is consistent with the widespread early onset of atherosclerosis [21,22], which at the beginning can only be detected at autopsy or with invasive techniques. In one such study using intravascular ultrasound, an amazing 17-21% of individuals aged 13 to 19 had evidence of atherosclerosis, and the numbers jumped to between 37% and 60% for the age group 20 to 29 [23]. A related question is simply, why does the so-called normal, healthy population have the observed distribution of CRP values in the first place [24]? There does not appear to be a detailed and useful answer. There is also the very important question of whether the circulating CRP is a risk factor per se, or just a marker, which can lead to confounding in the context of cardiovascular risk assessment by some inflammatory conditions but not others. Put another way, if an individual has a CRP value of, let's say, 5 mg/L which is reproduced to within 10-20% a month later in a second measurement, is this high CRP indicating some inflammatory condition which might have no direct connection to the risk of cardiovascular disease in this isolated case, or is any sustained source of inflammation significant, in the context of CVD, for anyone? Unfortunately, while much research has and is being done, and some answers have been proposed to these questions, these answers are really incomplete, hypothetical or so-called hypothesis generating. These questions in fact define a significant portion of the research frontier in this field, and the absence of evidence-based answers has caused some experts to take a position of "wait and see" in connection with the use of CRP for general screening. Studies that attempt to define the distribution of CRP in the "normal, healthy" population appear to contain a hidden variable, i.e. age. Kushner [12] has pointed out that a presumably non-inflammatory cause of CRP elevation is simply biologic aging. Wu et al [25], in a small study of 171 females and 183 males, found mean CRP levels of approximately 0.6 and 0.32 mg/L for males and females, respectively, in the age range of 20- 29, whereas in the age range of 70-79, the comparative mean values were approximately 1.3 and 1.7 mg/L. As a function of age, the values were roughly constant between 20 and 49 (mean 0.43 ± 0.42) and then jumped dramatically at about 50 years to give the much higher values (mean 1.3 ± 1.27), with women now higher than men, on average. There is considerable additional evidence that a minimal acute phase response may be a marker of biologic aging [12]. If only one CRP measurement is made, a reasonable question to ask regards the variation one might expect if instead, a series of measurements were made over an extended period. Clearly, the ideal test would give a set of values with, hopefully, a small enough variation so that one would remain in a given quintile, or at least show a variation of less than the average width of the lower quintiles. Because the measurement of CRP is being seriously proposed as a component of risk assessment for CVD, there have been several studies that address this obvious and important question [26,27,28,29,30,31]. In one study [27] of 10 men and 10 women, deemed healthy, aged 24-58, a series of CRP measurement over six months showed substantial intra-individual variations. If we use Rifai and Ridker's [19] quintiles, then 20/20 individuals exhibited a variation that covered two quintiles, and 17/20 covered three quintiles. Six individuals had a variation that spanned all five quintiles (approximate values taken from figures, references [27,28]. In a recent study by Ockene et al [26], of 113 individuals studied over a year, the within-subject standard deviation was 1.2 mg/L. Thus, if one had an average of say 2.0 mg/L, then just one standard deviation up or down would yield values of 0.8 and 3.2 mg/L, which covers three Rifai-Ridker quintiles. It does not seem practical to base a risk assessment protocol intended for general use on a large number of repeated tests. Two tests, spaced a month or two apart, would seem to be the practical limit in the normal clinical setting. The study by Ockene et al [26] also looked at the agreement between just two measurements three months apart. They observed that while about 63% of the participants remained in the same quartile (note, not quintile), 28% moved up or down a quartile, and 7% moved up or down two quartiles. These results are disturbing from the standpoint of using CRP as a tool for risk assessment, although if a patient tests in the lowest or highest quintile or quartile, this information can be used with more confidence than if the result was in a middle quartile or quintile, where the intra-individual variation could conceal the fact that the patient could possibly be in fact at high risk or low risk. Intra-individual variation may prove to be a major stumbling block in the use of CRP for CVD risk assessment, and highlights the difference between looking at the general picture presented by studies involving a large number of subjects and the problem of interpreting the casual, single measurement for a given individual. The intra-individual variation also underscores the fact that CRP is a non-specific marker of inflammation and that a high value can be caused by an inflammatory condition that may be transitory or asymptomatic. The key question, however seems to be--is elevated CRP from any cause a risk factor for CVD? While a direct pro-inflammatory effect of CRP on human endothelial cells has been observed in the laboratory [32], and while CRP has been found to mediate LDL uptake of macrophages implicated in atherosclerosis [33], studies like these and others [34,35,36] represent just the initial stages of research in this area, and no one knows the final answer. A number of other papers, short communications and editorials that have appeared in the medical-scientific literature in the past several years have expressed concerns regarding the proposed use of CRP as a screening tool for CVD [37,38,39,40]. The consensus, aside from the problems discussed above, concerns the absence of a detailed understanding of the role of CRP on a biologic or mechanistic level, especially in the context of the action of CRP per se in the initiation and promotion of CVD and whether inflammation unrelated directly to atherosclerosis, as compared to actual arterial inflammation, is relevant. PROS & CONS OF TESTING Is there enough evidence to justify requesting or agreeing to a CRP test? There does not appear to be a simple answer. However, in view of the large number of consistent studies indicating that it is an independent risk marker for CVD, and in view of the significantly elevated risk associated with high CRP and LDL on the one hand or elevated CRP and a high TC/HDL ratio on the other, it is difficult to dismiss or ignore the potential importance of this test. Consider two extreme situations:
REDUCTION OF CRP It is natural to conclude that since CRP appears to be a strong and significant risk factor for CVD, then reducing the blood level of this protein is obviously beneficial, but this is a fallacious line of reasoning. In fact there are no large intervention studies specifically linking CRP reduction with adverse cardiovascular events as endpoints, where there are no questions regarding other actions associated with the intervention that might reduce events independent of the reduction of CRP. For example, the statin class of cholesterol lowering drugs reduces CRP, but this does not prove that the reduction in observed adverse cardiovascular events is thus directly due even in part to this reduction in CRP. In fact, it is thought that the statin drugs have a multiplicity of effects, both good and bad (the various side effects, some of which can be serious or life-threatening). The actual direct benefit derived specifically from lowering the circulating level of CRP is presumably unknown, since the drug in question could produce the observed reduction in adverse events by a mechanism independent of CRP lowering. Nevertheless, it can be argued that there is nothing to loose and perhaps much to be gained by reducing elevated CRP levels, provided the actions have little or no risk or side effects. There are a number of non-pharmaceutical interventions or actions with the potential for reducing CRP levels. Several studies indicate regular exercise can lower levels [41,42], and that in fact there is an inverse correlation between fitness, as measured with treadmill tests, and CRP levels in both men and women [43,44]. Since CRP levels correlate with body mass index [6] ( BMI--weight in kg divided by the square of height in meters), a program of weight reduction, especially for those with BMI over 26, would be indicated. Smoking is strongly correlated with CRP, which provides one of many reasons for smoking cessation. Large daily doses of vitamin E (1200 IU) have been found to dramatically reduce CRP levels [45]. In fact, the percentage decrease observed with vitamin E exceeds that obtained by most pharmaceutical interventions [46]. Unfortunately, the study quoted did not investigate dose dependence, and some would view 1200 IU/day as high. The omega-3 essential fatty acids have been found to be both anti-inflammatory and to decrease serum CRP [47,48,49]. Dietary sources of omega-3 fats include fish, fish oil, canola oil, various nuts—especially walnuts, and ground flax seeds or flax seed oil. Alcohol and possibly other constituents of alcoholic drinks have an anti-inflammatory effect when consumed in moderation. Both non-drinkers and heavy drinkers have been found to have higher CRP levels than moderate drinkers, who in fact derived cardiovascular protection from alcohol along with the reduction in CRP levels [50]. Avoiding stress and taking action to resolve causes of depression are important, since there is a significant link with both [12,13,51]. The connection of CVD risk (and thus frequently elevated CRP) with infections is complex and the subject of much current research [52]. It can be argued that it may be wise to deal with dental infections, although the link between CHD and periodontal disease is far from clear [53,54]. However, research just published [55] based on an analysis of data derived from the Health Professionals' Follow-Up Study, found an increased risk of ischemic stroke to be associated with periodontal disease and tooth loss. In general, suspected chronic infections should be brought to the attention of the individual's physician and treatment discussed, at least in part, in the context of the potential for an enhanced CVD risk, even though the strength of the link between infections and CVD risk is still very much the subject of debate and research. Finally, in one large study aspirin was found effective in reducing both CRP and adverse cardiovascular events, especially for men with the highest CRP levels [18]. This observation in fact suggests that aspirin may have benefits over and above its well known anti-platelet effect, which involves interference with thrombus formation by platelets, and is the rationale for its widespread promotion and use in preventive medicine, in spite of the small but significant risk of adverse gastrointestinal bleeding and hemorrhagic stroke. Unfortunately, the effect of aspirin on CRP levels is uncertain, since the data from available studies are in fact inconsistent [56,57]. In addition, the current U.S. consensus on the use of aspirin for primary prevention of cardiovascular events [58] concludes that the balance of benefit vs. harm is most favorable in patients at high risk of CHD (those with a 10-year risk equal to or greater than 6%, presumably calculated from the Framingham study data [17] ). Dr. Stephen Sinatra, a practicing cardiologist, faculty member of the University of Connecticut Medical School and author of the recent book "Heart Sense for Women" [59], recommends a natural approach to reducing CRP which is described on his web site [60]. Sinatra was one of the early advocates of measuring CRP as part of the blood work-up for both heart patients and individuals presumed disease free [59]. CONCLUSIONS High CRP levels have been associated with an increased risk of future heart attacks, ischemic stroke, and peripheral arterial disease. However, there is no clear consensus as to whether a single screening test for CRP is useful as a diagnostic tool. The diagnostic value of CRP screening can be improved by performing two tests a month or so apart and by including both CRP and the cholesterol level ratio (TC/HDL) in the final risk assessment, perhaps in conjunction with a Framingham risk calculation. The lifestyle modifications that favorably impact CRP levels will be recognized by many readers as those that have also been widely discussed and advocated as part of a general approach to good health [61] and to decreasing the risk of cardiovascular disease. Some as well are frequently recommended as part of a non-pharmaceutical approach to reducing the risk associated with an unfavorable lipid profile [59,61]. It is common knowledge that about half of all individuals experiencing heart attacks have normal blood lipid profiles. A good example was described above [16]. It has been frequently suggested in the literature that one of the missing pieces in the puzzle is in fact CRP, independent of whether or not it acts as merely a marker, or is active per se, or both. Closely related to this hypothesis is the growing evidence that atherosclerosis is, at least in part, an infectious, inflammatory and autoimmune disease [1,62]. Research now in progress will almost certainly help clarify the picture.
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International Health News is published monthly by Hans R. Larsen MSc ChE 1320 Point Street, Victoria, BC, Canada V8S 1A5 Phone: (250) 384-2524 E-mail: health@pinc.com URL: http://www.yourhealthbase.com ISSN 1203-1933.....Copyright © 2003 by Hans R. Larsen International Health News does not provide medical advice. Do not attempt self- diagnosis or self-medication based on our reports. Please consult your health-care provider if you wish to follow up on the information presented. |