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Nutritional Supplement Program Halts Progression of Early Coronary Atherosclerosis Documented by Ultrafast Computed Tomography

  • Dr. Rath Health Foundation

Abstract and Figures

The aim of this study was to determine the effect of a defined nutritional supplement program on the natural progression of coronary artery disease. This nutritional supplement program was composed of vitamins, amino acids, minerals, and trace elements, including a combination of essential nutrients patented for use in the prevention and reversal of cardiovascular disease. The study was designed as a prospective intervention before-after trial over a 12 month period and included 55 patients (age 44-67) with various stages of coronary heart disease. Changes in the progression of coronary artery calcification before and during the nutritional supplement intervention were determined by Ultrafast Computed Tomography (Ultrafast CT). The natural progression rate of coronary artery calcification before the intervention averaged 44% per year. The progression of coronary artery calcification decreased on average 15% over the course of one year of nutritional supplementation. In a sub-group of patients with early stages of coronary artery disease, a statistically significant decrease occurred, and no further progression of coronary calcification was observed. In individual cases, reversal and complete disappearance of previously existing coronary calcifications were documented. This is the first clinical study documenting the effectiveness of a defined nutritional supplement program in halting early forms of coronary artery disease within one year. The nutritional supplement program tested here should be considered an effective and safe approach to prevention and adjunct therapy of cardiovascular disease.
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Nutritional Supplement Program Halts Progression of
Early Coronary Atherosclerosis Documented by Ultrafast
Computed Tomography
Aleksandra Niedzwiecki Ph.D. and Matthias Rath M.D.
Published in Journal of Applied Nutrition, 1996. Vol. 48 (pp 68-78)
According to the World-Health Organization, over 12 million people die every year from heart attacks, strokes
and other forms of cardiovascular disease.1
Current concepts of the pathogenesis of cardiovascular
disease focus on elevated plasma risk factors damaging the vascular wall and thereby initiating
atherogenesis and cardiovascular disease.2-4 Accordingly, drugs lowering cholesterol and modulating
other plasma risk factors have become a predominant therapeutic approach in the prevention of
cardiovascular disease.
A new scientific rationale about the initiation of atherosclerosis and cardiovascular disease was
proposed by one of us5,6. It can be summarized as follows: cardiovascular disease is primarily caused
by chronic deficiencies of vitamins and other essential nutrients with defined biochemical properties,
such as coenzymes, cellular energy carriers, and antioxidants.7,8 Chronic depletion of these essential
nutrients in endothelial and vascular smooth muscle cells impairs their physiological function. For
example, chronic ascorbate deficiency, similar to early scurvy, leads to morphological impairment of
the vascular wall and endothelial microlesions, histological hallmarks of early atherosclerosis. 9-11
Consequently, atherosclerotic plaques develop as the result of an overcompensating repair mechanism
comprising deposition of systemic plasma factors as well local cellular responses in the vascular
wall.5,6 This repair mechanism is primarily exacerbated at sites of hemodynamic stress, explaining
the predominantly local development of atherosclerotic plaques in coronary arteries and myocardial
infarction as the most frequent clinical manifestation of cardiovascular disease.
Animal studies have confirmed this scientific rationale for the combination of ascorbate with other
essential nutrients in the prevention and treatment of cardiovascular disease.12
Subjects and Methods
A total of 55 patients, 50 men and 5 women, with documented coronary artery disease assessed by
Ultrafast CT, were recruited for the study. The inclusion criterion was the availability of a high quality
Ultrafast CT scan from a previous visit to the Heart Scan facility in South San Francisco. At the
beginning of the study each patient completed a comprehensive questionnaire, which was updated
after six months and after 12 months. This questionnaire included medical history, previous cardiac
events, and cardiovascular risk factors, as well as individual life style data. Specific questions related
to the patientsÕ regular diet, such as strictly vegetarian diet, predominantly fruits and vegetables,
predominantly meat, fish or poultry; the daily intake of different vitamins and other essential
nutrients; and the frequency of physical exercise by the patient. The laboratory tests available
documented a heterogeneous population with respect to plasma cholesterol and triglycerides. About
half of the patients were taking different types of prescription medication, including calcium
antagonists, nitrates, betablockers, and cholesterol-lowering drugs. Before entering the study, the
patients were instructed not to change their diet or lifestyle other than adding the nutritional
supplement program tested. Any changes were to be documented in their questionnaires. Compliance
with the nutritional supplement program was monitored in the questionnaires, through telephone calls
and during the control visits.
Composition and Administration of Nutritional Supplement Program
The following daily dosages of nutritional supplements were taken for a period of one year: Vitamins:
Vitamin C 2700 mg, Vitamin E(d-Alpha-Tocopherol) 600 IU, Vitamin A (as Beta-Carotene) 7,500
IU, Vitamin B-1 (Thiamine) 30 mg, Vitamin B-2 (Riboflavin) 30 mg, Vitamin B-3 (as Niacin and
Niacinamide) 195 mg, Vitamin B-5 (Pantothenate) 180 mg, Vitamin B-6 (Pyridoxine) 45 mg, Vitamin
B-12 (Cyanocobalamin) 90 mcg, Vitamin D (Cholecalciferol) 600 IU. Minerals: Calcium 150 mg,
Magnesium 180 mg, Potassium 90 mg, Phosphate 60 mg, Zinc 30 mg, Manganese 6 mg, Copper 1500
mcg, Selenium 90 mcg, Chromium 45 mcg, Molybdenum 18 mcg. Amino acids: L-Proline 450 mg, L-
Lysine 450 mg, L-Carnitine 150 mg, L-Arginine 150 mg, L-Cysteine 150 mg. Coenzymes and other
nutrients: Folic Acid 390 mcg, Biotin 300 mcg, Inositol 150 mg, Coenzyme Q-10 30 mg, Pycnogenol
30 mg, and Citrus Bioflavonoids 450 mg.
Monitoring of Coronary Artery Disease
The extent of coronary calcification was measured non-invasively with an Imatron C-100 Ultrafast CT
scanner in the high-resolution volume mode, using a 100- millisecond exposure time. ECG triggering
was used so that each image was obtained at the same point in the diastole, corresponding to 80% of
the RR interval. In each scan, 30 consecutive images were obtained at 3-mm intervals beginning 1 cm
below the carina and progressing caudally to include the entire length of the coronary arteries. The
scans at study entry and after 6 and 12 months of the study included a second scan sequence of 30
images at 3 mm intervals across the entire heart. The 30 images of the second scan were taken
between the 3 mm intervals of the first scan resulting in a scanning of the heart at an interval of 1.5
mm. Total radiation exposure using this technique was <1rad per patient (<.01Gy).
The scan threshold was set at 130 Hounsfield units (Hu) for identification of calcified lesions. The
minimum area to differentiate calcified lesions from CT artifact was 0.68 mm2. The lesion score, also
designated Coronary Artery Scanning (CAS) score, was calculated by multiplying the lesion area by a
density factor derived from the maximal Hounsfield unit within this area.13 The density factor was
assigned in the following way: 1 for lesions with a maximal density with 130-199 Hu, 2 for lesions
with 200-299 Hu, 3 for lesions with 300-399 Hu and 4 for lesions > 400 Hu. The total calcium areas
and CAS scores of each Ultrafast CT scan were determined by summing individual lesion areas or
scores from the left main, left anterior descending, circumflex, and right coronary artery.
Several studies have confirmed an excellent correlation of the extent of coronary artery disease as
assessed by Ultrafast CT scanning when compared to angiographic and histomorphometric
methods.13-15 Considering the accuracy and the non-invasive approach, Ultrafast CT was the method
of choice for an intervention study that included early, asymptomatic stages of coronary artery
Statistical Analysis
The growth rate of coronary calcifications was calculated as the quotient of the differences in the
calcification areas or CAS scores between two scans divided by the months between these scans
according to the formula (Area2-Area1):(Date2-Date1), or (CAS score2-CAS score1):(Date2-Date1)
respectively. The data were analyzed using standard formulas for means, medians, and standard error
of the means (SEM). PearsonÕs correlation coefficient was used to determine the association between
continuous variables. One tailed Student t-test was used to analyze differences between mean values,
with a significance defined at <0.5. Progression of calcification was predicted by linear extrapolation.
The distribution of the growth rate of CAS scores was described by a smooth curve resulting from a
third order polynominal fit (y=a + bx3, where a = 0.9352959, b = 8.8235 x 10-5).
The aim of this study was to determine the effect of a defined nutritional supplement program on the
natural progression of coronary artery calcification particularly in its initial stages as measured by
Ultrafast CT. We therefore evaluated the results of the entire study group (n=55) and of a subgroup of
21 patients with early coronary artery calcification, as defined by a CAS score of <100.
Table 2 separately lists the characteristics of the study population assessed by the questionnaire for all
patients and for a subgroup with early coronary artery disease.
Table 1.
Figure 1.
This is the first intervention study using Imatron's Ultrafast CT technology. One of the first aims of
this study was to determine the rate of natural progression of coronary calcium deposits in situ ,
without the intervention of the nutritional supplement program. Figure 1 shows the distribution of the
monthly progression of calcifications in the coronary arteries of all 55 patients in relation to their CAS
score at study entry.
We found that the higher the CAS score was initially, without intervention, the faster the coronary
calcification progressed. Accordingly, the average monthly growth rate of coronary calcifications
ranged from 1 CAS score per month in patients with early coronary heart disease to more than 15
CAS score per month in patients with advanced stages of coronary calcifications. The growth pattern
of coronary calcifications can be described as a third order polynomial fit curve. The exponential
shape of this curve signifies a first quantification of the aggressive nature of coronary atherosclerosis
and emphasizes the importance of early intervention.
The changes in the natural progression rate of coronary artery calcification before the nutritional
supplement program (-NS) and after one year on this program (+NS) are shown in Figure 2. The
results are presented separately for the calcified area and the CAS score.
As presented in Figure 2.a. the average monthly growth of calcified areas for all 55 patients decreased
from 1.24 mm2/month (SEM +/- 0.3) before the nutritional supplement program (-NS) to 1.05
mm2/month (+/- 0.2) after one year on this program (+NS).For patients with early coronary artery
disease (Figure 2b), the average monthly growth of the calcified area decreased from 0.49 mm2/month
(+/- 0.16) before taking the nutritional supplements (-NS) to 0.28 mm2/month (+/- 0.09) after one year
on this program (+NS).
Figure 2.
As shown in Figure 2.c the average monthly changes in the total CAS score (calcified area X density
of calcium deposits) for all 55 patients had decreased after one year on the nutritional supplement
program by 11%, from 4.8 CAS score/month (SEM +/-0.97) before the program (-NS) to 4.27 CAS
score /month(+/- 0.87) (+NS). In patients with early coronary artery disease (Figure 2.d) the average
monthly growth of the total CAS score decreased during the same time by as much as 65%, from 1.85
CAS score /month (+/-0.49) before the nutritional supplement program (-NS) to 0.65 CAS score
/month (+/- 0.36) on this program (+NS). The slow-down of the progression of coronary calcification
during this nutritional supplement intervention for CAS scores of patients with early coronary artery
disease was statistically significant (p<0.05)(Figure 2.d). For the other three sets of data the decrease
of coronary calcifications with the nutritional supplement program was evident; however, largely due
to the wide range of calcification values at study entry reflecting the different stages of coronary artery
disease, it did not reach statistical significance.
It is noteworthy that the decrease in the CAS scores during intervention with nutritional supplements
were more pronounced than for the calcified areas. This indicates a decrease in the density of calcium
in addition to a reduction in the area of coronary calcium deposits during nutritional supplement
Ultrafast CT scans at the beginning of the study and after 12 months on the nutritional supplement
program, were complemented by a control scan after 6 month, allowing for additional insight into the
time required for the nutritional supplements to exert their therapeutic effect. This additional
evaluation was particularly important for early forms of coronary artery disease, because any
therapeutic approach that can halt progression of early coronary calcification would ultimately prevent
myocardial infarctions.
Figure 3 shows the average coronary calcification areas (Figure 3.a) and total CAS scores (Figure 3.b)
for patients with early coronary artery disease measured during different scanning dates before and
during the course of the study. The actual coronary calcification values for areas and total CAS scores
during nutritional supplement intervention are compared to the predicted values obtained from linear
extrapolation of the growth rate without intervention. The letters A to D mark the different time points
at which Ultrafast CT scans were performed. AB represents the changes in coronary calcification
before intervention with nutritional supplement for the areas (Figure 3.a) and CAS scores (Figure 3.b).
Accordingly, BC represents calcification changes during the first six months on the nutritional
supplement program and CD changes during the second six months on the program. The calculated
progression rate for coronary calcifications without therapeutic intervention by the nutritional
supplement program is marked by a dotted line (B through F).
As seen in Figure 3.a without the nutritional supplement program, the average area of coronary
calcifications in patients with early coronary artery disease increased from 17.62 mm2 (+/- 1.0) at
time point A to 23.05 mm2 (+/- 1.8) at time point B. Thus, the annual extension of calcified areas
without intervention was assessed with 31 %. At this progression rate, the average calcified area
would reach 26.3 mm2 after six months (point E) and 29.8 mm2 after twelve months (point F). The
nutritional supplement intervention, resulted in an average calcified area of 25.2 mm2 (+/-2.2) after
six months and of 27.0 mm2 (+/-1.7) after 12 months, reflecting a 10% decrease compared to the
predicted value.
Figure 3.
Analogous observations were made for the total CAS before and during the nutritional supplement
program. Figure 3.b shows that the CAS score before the nutritional supplement program increased by
44% per year, from 45.8 (+/- 3.2) (point A) to 65.9 mm2 (+/- 5.2) (point B). At this progression rate
the total CAS score, without the nutritional supplement program, would reach an average of 77.9 after
six months (point E) and of 91 (point F) after twelve months. In contrast to this trend the actual CAS
score values measured with the nutritional supplement program were 75.8 (+/-6.2) after 6 months
(point C) and 78.1 (+/-5.1) after 12 months (point D). Thus, the progression of coronary calcification
as determined by the total CAS scores decreased significantly during the second six months of
nutritional supplement intervention (CD). The total score after twelve months on the nutritional
supplement program was only 3% higher than after six months (CD), as compared to the projected
increase of 17% (EF), indicating that during the second six months on the nutritional supplement
program the process of coronary calcification has practically stopped.
Figure 4 shows the actual Ultrafast CT scans of a 51 year old patient with early, asymptomatic,
coronary artery disease. The patientsÕ first Ultrafast CT scan was performed in 1993 as part of an
annual routine check-up. The scan film revealed small calcifications in the left anterior descendent
coronary artery as well as in the right coronary artery. The second CT scan was performed one year
later at which time the initial calcium deposits had further increased. Figure 4.a shows two Ultrafast
CT scan images taken before the nutritional supplement program. Subsequently, the patient started on
the nutritional supplement program. About one year later the patient received a control scan. At this
time point, coronary calcifications were not found (Figure 4b), indicating the natural reversal of
coronary artery disease.
Figure 4.
This is the first study that provides quantifiable data from in situ measurements about the natural
progression rate of coronary artery disease. Although atherosclerotic plaques have a complex
histomorphological composition, calcium dispersion within these plaques has been shown to be an
excellent marker for their advancement.11,13 Our study determined that the calcified vascular areas
expand at a rate between 5 mm2 (early atherosclerotic lesions) and 40 mm2 (advanced atherosclerotic
lesions). Before the nutritional supplement program the average annual increase of total coronary
calcification was 44% (Figure 1). Considering the exponential increase of coronary calcification, it is
evident that the control of cardiovascular disease has to focus on early diagnosis and early
Today, the diagnostic assessment of individual cardiovascular risk is largely confined to the
measurement of plasma cholesterol and other risk factors with little correlation to the extent of
atherosclerotic plaques. More accurate methods, such as coronary angiography, are confined to
advanced, symptomatic, stages of coronary artery disease. Ultrafast CT provides the diagnostic option
to quantify coronary artery disease non-invasively in its early stages.14,15
The most important finding of this study is that coronary artery disease can be effectively prevented
and treated by natural means. This nutritional supplement program was able to decrease the
progression of coronary artery disease within the relatively short time of one year, irrespective of the
stage of this disease. Most significantly, in patients with early coronary calcifications this nutritional
supplement program was able to essentially stop its further progression. In individual cases with small
calcified deposits, nutritional supplement intervention led to their complete disappearance (Figure 4).
We postulate that the nutritional supplement program tested in this study initiates the reconstitution of
the vascular wall. Restructuring of the vascular matrix is facilitated by several nutrients tested, such as
ascorbate (vitamin C), pyridoxine (vitamin B-6), L-lysine, and L-proline, as well as the trace element
copper. Ascorbate is essential for the synthesis and hydroxylation of collagen and other matrix
components,16-18 and can be directly and indirectly involved in a variety of regulatory mechanisms
in the vascular wall from cell differentiation to distribution of growth factors.19,20 Pyridoxine and
copper are essential for the proper cross-linking of matrix components.8 L-lysine and L-proline are
important substrates for the biosynthesis of matrix proteins; they also competitively inhibit the binding
of lipoprotein(a) to the vascular matrix, facilitating the release of lipoprotein(a) and other lipoproteins
from the vascular wall.5,12,21 Ascorbate and -tocopherol have been shown to inhibit the proliferation
of vascular smooth muscle cells.22-24 Moreover, tocopherols, beta-carotene, ascorbate, selenium and
other antioxidants scavenge free radicals and protect plasma constituents, as well as vascular tissue,
from oxidative damage.25,26 In addition, nicotinate, riboflavin, pantothenate, carnitine, coenzyme Q-
10, as well as many minerals and trace elements, function as cellular cofactors in form of NADH,
NADPH, FADH, Coenzyme A and other cellular energy carriers.8 The results of this study confirm
that maintaining the integrity and physiological function of the vascular wall is the key therapeutic
target in controlling cardiovascular disease. This also corroborates early angiographic findings that
supplemental vitamin C may halt the progression of atherosclerosis in femoral arteries.27
These conclusions are even more relevant since deficiencies of essential nutrients are common.28,29
Moreover, many epidemiological and clinical studies have already documented the benefits of
individual nutrients in the prevention of cardiovascular disease.30-35 Compared to the high dosages
of vitamins used in some of these studies the amounts of nutrients used in this study are moderate,
indicating the synergistic effect of this program.
In this context, it seems appropriate to critically review some of the approaches currently used in the
primary and secondary prevention of cardiovascular disease, including the extensive use of
cholesterol-lowering drugs. An intervention study including lovastatin was performed with a highly
selected group of hyperlipidemic patients, representing only an extremely narrow fraction of a normal
population.36 More recently, the reduction of myocardial infarctions and other cardiac events in
patients taking simvastatin, led to recommendations for its long-term use even by normolipidemic
patients.37 However, because of their potential side-effects, the recommended use of these drugs has
now been restricted to patients at high short term risk for coronary heart disease.38
Similarly, certain natural approaches to prevention of cardiovascular disease deserve a critical review.
A program of rigorous diet and exercise program claims to be able to reverse coronary heart
disease.39 However, the published study does not provide compelling evidence documenting the
regression of coronary atherosclerosis. Thus, the improved myocardial perfusion shown in that study,
was likely the result of the physical training program, leading to an increased ventricular ejection
fraction and an increased coronary perfusion pressure.
Considering the urgent need for effective and safe public health measures towards the control of
cardiovascular disease, the validity of this study is of particular importance. In light of this, the
following study elements are noteworthy.
1 The patients in this study served as their own controls before and during nutritional supplement
intervention, thereby minimizing undesired co-variables such as age, gender, genetic predisposition,
diet or medication.
2 Ultrafast CT has been extensively validated to assess the degree of coronary atherosclerosis, and it
allowed quantification of coronary atherosclerotic plaques in situ.13-15 This diagnostic technique also
minimizes errors as they occur in angiography studies in which vasospasms, formation or lysis of
thrombi, and other events cannot be differentiated from progression or regression of atherosclerotic
plaques. Moreover, Ultrafast CT provides valuable information about the morphological changes
during progression and regression of atherosclerotic plaques, by quantifying not only the area of
coronary calcifications but also their density. Furthermore, the automatic CT measurements of
coronary calcifications eliminates human error in the evaluation of the data.
In summary, the results of this study imply that coronary heart disease is a preventable and essentially
reversible condition. This study documents that coronary artery disease could be halted in its early
stages by following this nutritional supplement program. These results were achieved within one year,
suggesting that additional therapeutic benefits in patients with advanced coronary artery disease can
be obtained by an extended use of this program. The continuation of this study is currently under way
to document these effects. This nutritional supplement program signifies an effective and safe
approach for the prevention and adjunct therapy of cardiovascular disease.
We are grateful to Jeffrey Kamradt for his help in coordinating this study. Douglas Boyd Ph.D., Lew
Meyer Ph.D. from Imatron/HeartScan., South San Francisco, for helping to plan the study and
providing the HeartScan facility; Lauranne Cox, Susan Brody, and Tom Caruso for their collaboration
in conducting the heart scans. Dr. Roger Barth and Bernard Murphy for their assistance in planning
the study, as well as to Martha Best for her secretarial assistance.
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... In a pilot clinical study involving patients with elevated plasma Lp(a) levels, vitamin C was found to lower its levels in 9 out 11 patients on average by 27%, with a median value also of 27% [76]. On the basis of an improved understanding on the pathogenesis of CVD, Rath proceeded to define a new therapeutic approach for reducing the risk of CVD with nutritional supplements. ...
... Both amino acids could facilitate a release of deposited Lp(a) and also other atherogenic lipoproteins from the vas-cular wall. The therapeutic implication is the non-invasive reversal of existing CVD with nutritional supplements[72].Following this, Rath and Niedzwiecki[76] conducted a clinical trial to determine the effect of a defined nutritional supplement program on the natural progression of coronary artery disease. This nutritional supplement program was comprised of vitamins, amino acids, minerals and trace minerals, and other essential nutrients. ...
Full-text available
Atherosclerosis is the precedent to ischemic heart disease, which may lead to angina, myocardial infarct, or heart failure; or to ischemic cerebrovascular disease, which may lead to stroke. The prevailing belief underlying conventional approaches to treatment of atherosclerosis and its sequel is that a diet high in cholesterol and saturated fat is the main contributory factor, triggering cholesterol build up in the intima of the blood vessels. Over the last 60 years, the blame has shifted from fats, to saturated fats, to low-density lipoprotein (LDL), and finally to oxidized LDL (Ox-LDL). Therapy has been predominantly aimed at lowering cholesterol and control of risk factors. However, there is an alternative hypothesis about the cause of heart disease linking it to the weakening of the vascular collagen matrix at the sites of high hemodynamic stress (coronary arteries) which triggers the infiltration of lipoprotein(apo) [Lp(a)] and plaque development. Accordingly, the vascular deposition of large molecules such as Lp(a) and atherosclerosis is the result of the body’s endogenous protective mechanism to reinforce the weakened artery walls. Understanding this mechanism may guide the natural prevention of this disease and form the basis for developing effective therapeutic strategies aiming at natural reversal of atherosclerosis through the reinforcement of the vascular wall structure as its primary goal. This reappraisal of atherosclerosis and the cholesterol theory looked at the historical development of the theory, and the Rath and Pauling unified theory of cardiovascular disease.
... Also, dietary vitamin C is essential in preventing the deposition of lipoproteins in the vascular wall and atherosclerosis in genetically engineered mice, mimicking human metabolism in relation to their inability to produce vitamin C and their expression of human lipoprotein(a) [14]. In a clinical study, a daily micronutrient supplement, including about 4 grams of vitamin C, was able to halt the progression of coronary calcifications in patients diagnosed with early coronary artery disease [15]. ...
Vascular calcification is a pathophysiological process that is associated with coronary atherosclerosis, and is a prognostic marker of cardiovascular morbidity and mortality. The process of arterial wall calcification is triggered and accompanied by pro-osteogenic phenotypical modifications of resident smooth muscle cells (SMC). Vitamin C (ascorbic acid) is an essential nutrient required to support the production of extracellular matrix components and maintain healthy connective tissue. In this study we investigated the effects of ascorbic acid on cultured human aortic SMC calcification process in vitro. Our results demonstrate that supplementation of SMC cultures with ascorbic acid significantly decreases calcium accumulation in SMC-produced and -deposited extracellular matrix. These effects were accompanied by a reduction in cell-associated alkaline phosphatase activity. Significantly, treatment of cultured SMC with HMG-CoA reductase inhibitors, simvastatin and mevastatin, resulted in increased calcium accumulation in cultured SMC. These effects were blocked by ascorbic acid. The effects of ascorbic acid supplementation on pro-osteogenic modification were compared in different cell types. Analysis of the expression of osteogenic markers in cultured human aortic SMC, human dermal fibroblasts and immortalized human osteoblasts (hFOB) revealed cell type-specific responses to ascorbate supplementation. We conclude that ascorbic acid supplementation can actively and beneficially interfere with the process of arterial wall calcification, with potential implications for human health.
... The concept of nutrient synergy means that the end result is better than the sum of the results using individual nutrients. This concept that produced positive effects with the micronutrient combination, has been demonstrated in previous studies [24,25,26]. As HIV and AIDS are very chronic conditions that indicate the destruction of the immune system, using a single micronutrient may not be as ideal as using a micronutrient combination to boost the immune system. ...
... The result of this study corroborates with the findings of Rath and Niedzwiecki [16] whereby a similar nutritional supplement program halted the progression of early coronary artery disease. A recent study on the effect of vitamin C on transgenic mice that mimic human pathophysiology [17] lends credence to the hypothesis of Rath and Pauling that the ...
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Heart failure is a progressive cardiovascular disorder and, in most cases, begins with atherosclerosis and ischemic heart disease. The prognosis of patients with heart failure is poor, even with improvement on the management of all forms of ischemic heart disease. There have been studies on heart failure using a single nutrient or a combination of multiple nutrients. Results are mixed. The aim of this study was to assess the influence of multiple micronutrient supplementation using the quality of life measure on patients with heart failure secondary to ischemic heart disease. This prospective case series followed 12 patients for a period between 3 to 8 months, using the Minnesota Living with Heart Failure Questionnaire (MLHFQ) as the sole outcome measure. The primary outcome was a score change over time between the start and endpoint of treatment. Change in MLHFQ mean total score was 27.08 ± 20.43 and mean symptoms score was 4.67 ± 3.34. Paired t-test showed a difference between baseline and endpoint of treatment (P < 0.001), which was statistically significant. A high dose of multiple micronutrients may have beneficial effects on cardiac function in patients with symptomatic heart failure. This study indicates the need for long-term controlled studies to test the efficacy and safety of this economic approach in managing heart failure.
... Rath and Niedzwiecki [86] demonstrated the effect of nutritional supplements (a combination of vitamins, minerals, and coenzymes) on progression of CAC in 55 persons. Patients treated with the nutritional supplements demonstrated an annual progression of 15%, while untreated patients progressed at a rate of 44%. ...
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Cardiovascular disease remains the leading cause of mortality in the US and worldwide, and no widespread screening for this number one killer has been implemented. Traditional risk factor assessment does not fully account for the coronary risk and underestimates the prediction of risk even in patients with established risk factors for atherosclerosis. Coronary artery calcium (CAC) represents calcified atherosclerosis in the coronary arteries. It has been shown to be the strongest predictor of adverse future cardiovascular events and provides incremental information to the traditional risk factors. CAC consistently outperforms traditional risk factors, including models such as Framingham risk to predict future CV events. It has been incorporated into both the European and American guidelines for risk assessment. CAC is the most robust test today to reclassify individuals based on traditional risk factor assessment and provides the opportunity to better strategize the treatments for these subjects (converting patients from intermediate to high or low risk). CAC progression has also been identified as a risk for future cardiovascular events, with markedly increased events occurring in those patients exhibiting increases in calcifications over time. The exact intervals for rescanning is still being evaluated.
Coronary heart disease (CHD) is the most common cause of morbidity and mortality in western nations and the majority of acute events occur unexpectedly in patients unaware of any underlying risk. Unfortunately, a large number of these asymptomatic patients fall outside of the known categories of risk as defined by the current clinical guidelines. Therefore, investigators have turned their attention to novel noninvasive methodologies to detect CHD in its preclinical stages. Electron beam tomography (EBT) is a radiological technology that permits noninvasive acquisition of high-resolution images of the coronary arteries without injection of contrast. Coronary atherosclerosis is vicariously identified via the presence of calcific deposits in the vessel wall. Although the relevance of the information collected with EBT imaging has been the source of considerable debate for several years, the medical community has recently shown an increasing interest in its potential applications. This chapter reviews the current state of the art of the technology, its clinical applications, current limitations, and future directions.
Coronary artery calcium is a marker of sub-clinical atherosclerosis and it is deposited via an active process similar to bone formation. Sequential non-contrast CT has been proposed as a method to accurately quantify and monitor progression of calcification. While interventions have generally failed to slow progression of calcification, it has become apparent that continued progression of CAC is associated with an increased risk of myocardial infarction and cardiac death. As a consequence, researchers have implemented sequential cardiac CT to follow the progression of coronary artery calcium in a variety of clinical settings and in some cases have reported encouraging results.
In the past years many different kinds of new foods have appeared on the German market. Two groups of them, functional foods and dietary supplements, are of special interest, as they are generally offered in order to improve health, performance or wellbeing. The initiatives which pushed forward functional foods as a group started in Japan, where special “health products” are developed and approved by the government as foods for special health use (FOSHU's). For these foods also special claims are allowed. In the USA, legislation was changed to enable the food industry to inform consumers in more detail about the possible health benefit of a certain food. Also so-called “health claims” were allowed, in which consumers learn about the suitability of special foods helping to reduce the risk of several diseases. Tentatively, functional foods can be regarded as a concept to design foods in order to provide an additional, scientifically proven benefit beyond that of meeting basic nutritional needs. In contrast dietary supplements are not ordinary foods, but pills or capsules. They offer substances or ingredients in concentrated form, and they are advertised to supplement an increased need of the human body for these substances. However, the great diversity of substances and the variance of concentrations and dosages, which can be found in dietary supplements suggest that there is no clear health promoting concept behind this particular kind of foods. One of the main problems with these new foods is the lack of transparency, i.e. the absence of an obligatory definition. By this, a straightforward discussion about advantages and disadvantages of these novelties is prohibited and the development of prudent products may be hindered. Moreover questions of effectiveness and safety of functional foods and dietary supplements have to be answered in a very specific way.
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Context.-In a previous study, we found that masking success was higher at a journal that masked reviewers to author identity. We hypothesized that masking policy or other factors could be associated with masking success. Objectives.-To evaluate differences in success of masking reviewers to author identity at 7 biomedical journals and to identify factors associated with these differences. Design.-Written questionnaire. Participants.-Reviewers at 3 journals with a long-standing policy of masking author identity (Annals of Emergency Medicine, Epidemiology, and Journal of the American Geriatrics Society) and 4 journals without a policy of masking author identity (Annals of Infernal Medicine, JAMA, Obstetrics & Gynecology, and Ophthalmology). Main Outcome Measures.-Masking success (percentage of reviewers successfully masked) and reviewer characteristics associated with masking. Results.-There was no significant difference in masking success between journals with a policy of masking (60%) and those without (58%) (P=.92). We found no association between masking success and a policy of masking when adjusted for the reviewer characteristics of age, sex, years of reviewing experience, number of articles published, number of articles reviewed, percentage of time spent in research, editorial experience, or academic rank (odds ratio [OR], 1.3; 95% confidence interval [CI], 0.64-2.8; P=.43). In multivariable analysis of reviewer characteristics, reviewers spending a greater percentage of time in research, the only significant predictor of masking success, were less likely to be successfully masked (OR, 1.01;95% CI, 1.00-1.02) (P=.04). Conclusions.-Masking success appears unrelated to a journal policy of masking, but is associated with reviewers' research experience and could be affected by other characteristics. Using reviewers with less research and reviewing experience might increase masking success, but the effect on review quality is unknown.
The data presented in this chapter provide evidence that non-invasive CT imaging can be used to monitor the effectiveness of medical therapy by following changes in burden of calcified plaque. Nonetheless, there are some limitations inherent with the technology currently available. There is a strong need to standardize the scoring methods and assess the equivalence of the existing CT equipment. Additionally, the rigid application of a density threshold of 130 HU to define the presence of vascular or valvular calcification in all patients limits our ability to identify more recent, less densely calcified and therefore softer plaques. Though further prospective studies will be necessary to confirm the clinical significance of the findings herein summarized, it is quite evident that the effectiveness of anti-atherosclerotic therapy can be gauged with sequential CT imaging. The application of this technology will greatly facilitate primary and secondary prevention studies by allowing a great reduction in the number of patients needed to show effectiveness of therapy. Simultaneously, a physician’s effort to implement preventive measures could be gratified by the ability to measure the effectiveness of the applied remedies. Interventions directed at modifying risk factors associated with atherosclerosis besides LDL such as small-density LDL, Lp(a), low HDL, elevated homocysteine levels, and use of anti-viral and anti-bacterial agents will likely be the focus of future research. With continued improvements in CT technology and expanded clinical experience, it is hoped that the role of coronary calcium in primary and secondary prevention will be further defined and become more readily accepted by a wider circle of physician users.
In Reply. —Dr Braun is correct in indicating the RR for coronary heart disease for the lowest folate level studied was statistically significant (P=.04) for women, but not for men. However, the test for trend was statistically significant for both men and women. Although stratum-specific RRs were higher for women compared with men, the 95% CIs around the point estimates for men and women overlapped. Moreover, a comparison of the sex-specific rate ratios is not the most appropriate means to assess interaction. To formally test the interaction of sex, folate, and coronary heart disease, we compared the goodness-of-fit of a model that incorporated this interaction with one that did not. The deviances were 581.76 and 584.53 for the "interaction" and "no-interaction" models, respectively. This difference can be assumed to follow a X2 distribution with degrees of freedom equal to the difference in the number of independent parameters in the 2
Objective: To review the findings and implications of studies of rodent carcinogenicity of lipid-lowering drugs. Data sources: Summaries of carcinogenicity studies published in the 1992 and 1994 Physicians' Desk Reference (PDR), additional information obtained from the US Food and Drug Administration, and published articles identified by computer searching, bibliographies, and consultation with experts. Study sample: We tabulated rodent carcinogenicity data from the 1994 PDR for all drugs listed as "hypolipidemics." For comparison, we selected a stratified random sample of antihypertensive drugs. We also reviewed methods and interpretation of carcinogenicity studies in rodents and results of clinical trials in humans. Data synthesis: All members of the two most popular classes of lipid-lowering drugs (the fibrates and the statins) cause cancer in rodents, in some cases at levels of animal exposure close to those prescribed to humans. In contrast, few of the antihypertensive drugs have been found to be carcinogenic in rodents. Evidence of carcinogenicity of lipid-lowering drugs from clinical trials in humans is inconclusive because of inconsistent results and insufficient duration of follow-up. Conclusions: Extrapolation of this evidence of carcinogenesis from rodents to humans is an uncertain process. Longer-term clinical trials and careful postmarketing surveillance during the next several decades are needed to determine whether cholesterol-lowering drugs cause cancer in humans. In the meantime, the results of experiments in animals and humans suggest that lipid-lowering drug treatment, especially with the fibrates and statins, should be avoided except in patients at high short-term risk of coronary heart disease.
Drug therapy for hypercholesterolaemia has remained controversial mainly because of insufficient clinical trial evidence for improved survival. The present trial was designed to evaluate the effect of cholesterol lowering with simvastatin on mortality and morbidity in patients with coronary heart disease (CHD). 4444 patients with angina pectoris or previous myocardial infarction and serum cholesterol 5·5-8·0 mmol/L on a lipid-lowering diet were randomised to double-blind treatment with simvastatin or placebo.Over the 5·4 years median follow-up period, simvastatin produced mean changes in total cholesterol, low-density-lipoprotein cholesterol, and high-density-lipoprotein cholesterol of -25%, -35%, and +8%, respectively, with few adverse effects. 256 patients (12%) in the placebo group died, compared with 182 (8%) in the simvastatin group. The relative risk of death in the simvastatin group was 0·70 (95% Cl 0·58-0·85, p=0·0003). The 6-year· probabilities of survival in the placebo and simvastatin groups were 87·6% and 91·3%, respectively. There were 189 coronary deaths in the placebo group and 111 in the simvastatin group (relative risk 0·58, 95% Cl 0·46-0·73), while noncardiovascular causes accounted for 49 and 46 deaths, respectively. 622 patients (28%) in the placebo group and 431 (19%) in the simvastatin group had one or more major coronary events. The relative risk was 0·66 (95% Cl 0·59-0·75, p<0·00001), and the respective probabilities of escaping such events were 70·5% and 79·6%. This risk was also significantly reduced in subgroups consisting of women and patients of both sexes aged 60 or more. Other benefits of treatment included a 37% reduction (p<0·00001) in the risk of undergoing myocardial revascularisation procedures.This study shows that long-term treatment with simvastatin is safe and improves survival in CHD patients.
Human cardiovascular disease (CVD) is the result of the accumulation of lipopro-tein(a), Lp(a), rather than of low density lipoprotein (LDL), in the vascular wall. It
Reducing the risk for cardiovascular disease (CVD) is a primary goal of any health care system in the industrialized world. The success of this world-wide effort will largely depend on the proper understanding of the mechanisms responsible for development of this disease. This paper marshals the scientific evidence for the predominant pathome-chanisms of CVD and presents new therapeutic approaches. Human atherosclerotic lesions are primarily composed of lipoprotein-a. The extracellular deposition of this lipoprotein directly parallels the extent of the atherosclerotic lesion. The frequency of this pathomechanism today is directly related to its efficacy as a defense mechanism during the evolution of man, particularly in stabilizing the vascular wall during ascorbate deficiency. The deposition of lipoprotein-a in form of largely intact particles implies the reversibility of this mechanism. On the basis of an improved understanding about the pathogenesis of CVD new therapeutic approaches are defined. Certain vitamins and amino acids are of particular importance for these approaches. Ascorbate is essential for preserving and restoring the integrity and stability of the vascular wall. Niacin and ascorbate were reported to lower lipoprotein-a plasma levels. It is proposed that this effect is mediated by NADPH. The amino acids L-lysine and L-proline competitively interfere with the binding of lipoprotein-a to constituents of the vascular wall and atherosclerotic lesions. The therapeutic use of these amino acids could prevent further buildup of lipoprotein-a accumulation in the vascular wall. More importantly, optimum concentrations of L-lysine and L-proline could release deposited lipoprotein-a but also other atherogenic lipoproteins from the vascular wall. This paper defines a new therapeutic goal: The pharmaceutical, non-invasive reversal of existing CVD with nutritional supplements.
Until now therapeutic concepts for human cardiovascular disease (CVD) were targeting individual pathomechanisms or specific risk factors. On the basis of genetic, metabolic, evolutionary, and clinical evidence we present here a unified pathogenetic and therapeutic approach. Ascorbate deficiency is the precon- dition and common denominator of human CVD. Ascorbate deficiency is the result of the inability of man to synthesize ascorbate endogenously in combination with insufficient dietary intake. The invariable morphological consequences of chronic ascorbate deficiency in the vascular wall are the loosening of the connective tissue and the loss of the endothelial barrier function. Thus human CVD is a form of pre-scurvy. The multitude of pathomechanisms that lead to the clinical manifestation of CVD are primarily defense mechanisms aiming at the stabilization of the vascular wall. After the loss of endogenous ascor- bate production during the evolution of man these defense mechanisms became life-saving. They counteracted the fatal consequences of scurvy and particularly of blood loss through the scorbutic vascular wall. These countermeasures constitute a genetic and a metabolic level. The genetic level is characterized by the evolutionary advantage of inherited features that lead to a thickening of the vascular wall, including a multitude of inherited diseases.
Chondrocytes enzymatically dissociated from 13-day-old mouse embryo tibia grow in monolayer culture with a fibroblast-like phenotype and express high levels of type I collagen. Chondrogenesis can be induced by transferring the adherent cells in suspension culture and maintaining them in the constant presence of mouse embryo extract. Round shaping of the cells and formation of multicellular aggregates rapidly follow the passage in anchorage-independent conditions. Cell differentiation is evidenced by a marked decrease in the level of type I collagen and by the induction of type II collagen which accumulates when ascorbic acid is included in the culture medium. The addition of the vitamin also triggers the aggregated chondrocytes to organize their extracellular matrix giving rise to a structure closely resembling the in vivo developing cartilage.
Tocopherols and tocotrienols (vitamin E) and ascorbic acid (vitamin C) as well as the carotenoids react with free radicals, notably peroxyl radicals, and with singlet molecular oxygen (1O2), this being the basis of their function as antioxidants. RRR-alpha-tocopherol is the major peroxyl radical scavenger in biological lipid phases such as membranes or low-density lipoproteins (LDL). L-Ascorbate is present in aqueous compartments (e.g. cytosol, plasma, and other body fluids) and can reduce the tocopheroxyl radical; it also has a number of metabolically important cofactor functions in enzyme reactions, notably hydroxylations. Upon oxidation, these micronutrients need to be regenerated in the biological setting, hence the need for further coupling to nonradical reducing systems such as glutathione/glutathione disulfide, dihydrolipoate/lipoate, or NADPH/NADP+ and NADH/NAD+. Carotenoids, notably beta-carotene and lycopene as well as oxycarotenoids (e.g. zeaxanthin and lutein), exert antioxidant functions in lipid phases by free-radical or 1O2 quenching. There are pronounced differences in tissue carotenoid patterns, extending also to the distribution between the all-trans and various cis isomers of the respective carotenoids. Antioxidant functions are associated with lowering DNA damage, malignant transformation, and other parameters of cell damage in vitro as well as epidemiologically with lowered incidence of certain types of cancer and degenerative diseases, such as ischemic heart disease and cataract. They are of importance in the process of aging. Reactive oxygen species occur in tissues and cells and can damage DNA, proteins, carbohydrates, and lipids. These potentially deleterious reactions are controlled in part by antioxidants that eliminate prooxidants and scavenge free radicals. Their ability as antioxidants to quench radicals and 1O2 may explain some anticancer properties of the carotenoids independent of their provitamin A activity, but other functions may play a role as well. Tocopherols are the most abundant and efficient scavengers of peroxyl radicals in biological membranes. The water-soluble antioxidant vitamin C can reduce tocopheroxyl radicals directly or indirectly and thus support the antioxidant activity of vitamin E; such functions can be performed also by other appropriate reducing compounds such as glutathione (GSH) or dihydrolipoate. The biological efficacy of the antioxidants is also determined by their biokinetics.