| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||
Discussion |
Cardiology Section, Department of Internal Medicine, Michigan State University College of Osteopathic Medicine and Heart Disease Prevention Program, Thoracic and Cardiovascular Institute, East Lansing, Michigan
Dr. David J. Strobl.
Part of the reason that the role of nutrition is not seriously investigated with regard to disease prevention may relate to conflicting information in the media, which leads to consumer confusion. A few years ago nutritionists were emphasizing the importance of polyunsaturated fats. Today, health professionals are telling people to include more monounsaturated fats in their diet. At one time, headlines warned that shrimp and shellfish were detrimental to health. Later, dietary intake of shrimp and shellfish was encouraged. Likewise, the low-fat, high-carbohydrate diet was replaced by the so-called Mediterranean diet as the diet of choice. Even supplements such as beta-carotene have come in and out of favor. The public doesn’t know what to do with this conflicting information. This situation creates a challenge for health professionals to ensure that the general public receives accurate, scientifically based information on which to make informed decisions.
Another issue is distinguishing between a marker for a disease and a target for intervention. For example, male pattern baldness is a marker for coronary disease, not a target for intervention. Likewise, novel risk factors such as homocysteine and C-reactive protein are markers for coronary heart disease. Another example of a marker is the increase in uric acid in people with syndrome X. In contrast, elevated low-density lipoprotein (LDL) cholesterol level is a target for intervention. Clinical trials are needed to differentiate markers for disease from targets of intervention.
Dr. Robert P. Heaney.
Dr. Zemel, why do you think the "Calcium for Pre-eclampsia Prevention" (C-PEP) trial in this country failed? Does it reflect a threshold effect?
Dr. Michael B. Zemel.
Yes. The failure to find a significant beneficial effect of calcium on pregnancy outcome in this study is likely explained by the women’s already relatively high calcium intake of 1100 mg/day.
Dr. Kenneth D.R. Setchell.
What is the role of sunshine in 1,25 vitamin D status and what is the role of the latter in obesity?
Dr. Zemel.
Sunshine reduces, to some degree, 25-hydroxy vitamin D stores. It does not really have much influence on 1,25 dihydroxy vitamin D.
Dr. Heaney.
Sunshine has no effect on the 1,25 dihydroxy vitamin D level in otherwise healthy people. It raises the level of 25-hydroxy level, which is a precursor of 1,25 dihydroxy vitamin D. Primitive humans would have had very low 1,25 dihydroxy vitamin D levels but high 25-hydroxy vitamin D levels. This is exactly the opposite of what we see in African Americans in North America who have high 1,25 dihydroxy vitamin D levels, consistent with their propensity for obesity and hypertension, and low 25 hydroxy D levels. We do not understand the role of 25-hydroxy D as a precursor of paracrine function of 1,25 in a whole variety of tissues. We are focusing on 1,25 dihydroxy vitamin D as an endocrine hormone at the moment, but it clearly has other functions as well.
Dr. Bahram H. Arjmandi.
Dr. Zemel, you said low dietary calcium increases parathyroid hormone as well as 1,25 dihydroxy vitamin D, which increases the influx of calcium. If that is the case, how do you explain the phenomenon that during aging, as blood pressure increases, our cells become less responsive to agonists, such as epinephrine, in moving calcium?
Dr. Zemel.
You can see age-related increases in intracellular calcium. I think you have to separate the agonists in terms of the movement of calcium. There are multiple calcium channels, including passive calcium channels and voltage and receptor operated calcium channels. Then, there is a novel 1,25 vitamin D channel operated by a unique membrane vitamin D receptor. I don’t have any evidence that the responsiveness of this receptor changes with aging. Hypertension studies from the 1980s examined the efficacy on a whole range of both dihydropuridine and nondihydropuridine calcium channel intactness. In these studies, efficacy increased in the elderly, indicating fairly good preservation of voltage operated calcium channels, at least in the vasculature.
Dr. Keith B. Wheeler.
Dr. Zemel, with regard to your study showing that dairy foods were more effective than calcium supplements in regulating body fat, why didn’t dairy components such as conjugated linoleic acid (CLA) contributed to the beneficial effect of these foods, as opposed to the availability of the calcium?
Dr. Zemel.
I don’t believe that it is the availability of calcium because we equalized the calcium. It’s certainly not CLA because there was no CLA in our preparations. As to what other component in dairy foods might contribute to their beneficial effect on body fat, we are not quite sure yet. We just completed a study using a calcium-fortified cereal and a non-calcium-fortified cereal as the control. When we increased calcium to 1.2%, as in our high-calcium diet, by using a calcium-fortified cereal, we saw positive effects. But when we added just enough milk to increase the calcium from 1.2% to 1.3% percent (i.e., a trivial amount of milk), the extra 0.1% percent had a profound, synergistic effect on body fat reduction. I think that something other than simply the source, form, or bioavailability of calcium is involved. Perhaps the matrix effects of food components play a role. This would support the use of food as medicine rather than using surrogate nutrients as medicine.
Dr. Bridget Barrett-Reis.
What was the form of calcium in the cereal?
Dr. Zemel.
Calcium carbonate.
Dr. Marc L. Masor.
In infant nutrition, we note an interaction between fat and calcium. Human milk is very high in palmitic acid, and a number of our competitors have added palm olein oil. In palm olein oil, the palmitate tends to be in the 1 and 3 positions; consequently it releases a free fatty acid, which binds with calcium. There is a 10% difference in fat absorption and a 20% difference in calcium absorption between formulas that do and do not contain palm olein oil. Did you look at the fatty acid content of your diets and its effect on calcium?
Dr. Zemel.
Our experiments show that there is no difference in fecal energy, so we are not dealing with fat malabsorption.
Dr. Reis.
Dr. Keen, do you know what oils are in chocolate? Do different forms of chocolate have different types of oils that could be effective in platelet aggregation?
Dr. Carl L. Keen.
The principal fat in chocolate is stearic acid, which tends to have a relatively neutral effect on blood cholesterol levels. Despite chocolate’s reputation as a high fat food, long-term feeding trials consistently show that chocolate does not raise blood cholesterol levels. Some reports show that chocolate, at very high concentrations, affects the P-selectin in the plasma, but we have not seen that same effect. Also, we have used cocoa beverages, as opposed to typical chocolate product, which has a lot of butterfat. Cocoa beverage has little fat and, in fact, is relatively low in calories.
Dr. Strobl.
Doesn’t the butterfat in chocolate, which is high in saturated fat, raise LDL cholesterol levels?
Dr. Keen.
It is worth noting that a couple of long-term feeding trials of chocolate have not led to elevated LDL cholesterol levels. Perhaps the best study was by Kris-Etherton, who found no increase in LDL cholesterol and actually a small increase in high-density lipoprotein (HDL) cholesterol. At a recent symposium at the European cardiology meeting in Amsterdam, the consensus was that, although chocolate bars might not be advocated for heart patients, one should not feel guilty about eating chocolate. Chocolate may be one of those flavonoid-rich foods that has a bad reputation because of its fat content. Cocoa beverages may be another story. A cocoa beverage can contain 800 mg polyphenols and have about 50 calories per serving.
Dr. Vladimir Vuksan.
In our recently published study with cocoa (not chocolate) cereals, we found a beneficial effect on blood lipids and on the bowel. The effect on the bowel was comparable to that found with wheat bran.
Dr. Robert J. Nicolosi.
Weren’t these acute effects of the intervention trials?
Dr. Keen.
Yes. In contrast, the study by Kris-Etherton reported chronic effects, specifically reductions in LDL oxidation susceptibility.
Dr. Nicolosi.
I worry that clinical trials of antioxidants in a population that’s already consuming so many other antioxidants will not find additional benefits.
Dr. Keen.
I should have stressed that in all of our trials, we asked people to refrain from taking flavonoid-rich foods for at least 24 hours, and in one case for 3 days, before the study.
An interesting question relates to the amount of polyphenols needed to attain a benefit. A typical diet contains between 10 and 1000 mg of polyphenols. Some epidemiologic studies indicate that polyphenol intake is more than 200 to 300 mg/day.
Dr. Arjmandi.
Dr. Nicolosi, why are total cholesterol and vitamin E elevated in ovariectomized rats or hamsters?
Dr. Nicolosi.
It is well established that if animals are ovariectomized, LDL cholesterol increases. Because LDL cholesterol carries vitamin E, vitamin E also increases.
Dr. Setchell.
I’m amazed by the tremendous similarity between the flavonoids and the isoflavones in soy. We know that they both affect platelet-derived growth factors, clotting, and vascular reactivity, as well as exhibit antioxidant properties. Yet there are some striking differences in the overall behavior of these compounds, for example, in their absorption and bioavailability. Most of the absorption of flavonoids occurs in the stomach, which is not the case for isoflavones. If the bioavailability of flavonoids is about 10%, where does the remaining 90% of flavonoid intake go? In our kinetic studies of isoflavones, we can account for no more than 40% to 50% maximum of isoflavone intake. Is this also true for flavonoids? To increase the bioavailability of flavonoids from 10%, dietary matrix effects must be considered. For example, grapefruit juice markedly reduces the bioavailability of many things, including oral contraceptives. Dietary matrix is tremendously important in improving or interfering with the bioavailability of nutrients or food components.
Dr. Keen.
We estimate that the bioavailability of isoflavones is approximately 10%, which is strikingly higher than the percentage indicated in the literature. Peak absorption typically occurs at approximately 1 to 2 hours. We are doing experiments to learn more about the digestion and absorption of isoflavones and flavonoids. The rat is not a good model for studying polyphenols because its metabolism is quite different from that of humans.
Dr. Fabrizis Suarez.
Dr. Nicolosi, several dietary components influence plasma cholesterol levels. Some people are hyperresponders to diet and others are hyporesponders. Is there a specific dietary component that most people will be able to respond to?
Dr. Nicolosi.
Some individuals will respond with a change in blood cholesterol level to one nutrient and not to another, perhaps because of differences in metabolism. For example, individuals who respond more successfully to statins may be better able to inhibit cholesterol synthesis. For years, we have been looking for indices to help identify or define cholesterol responders and nonresponders in the population. In general, blood cholesterol-lowering neutraceuticals or drugs work best in individuals with initial or baseline high blood cholesterol levels. In terms of which neutraceuticals work best, plant sterols show consistent, hypocholesterolemic effects. In more than 30 trials, plant sterols have led to a consistent 10% to 15% reduction in LDL cholesterol levels. In contrast, more variability occurs with dietary fiber and soy protein. The dietary matrix or the population being studied may explain the inconsistent hypocholesterolemic effects of some dietary components. In general, the stanols seem to be the most consistent, effective compounds to lower blood cholesterol levels, which may be explained by the manner in which they are presented to the population.
| ||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
