Are Clinical Trials Misleading?

Written by Dr. Steve Chaney on . Posted in clinical trials

Is Most Of What You’ve Been Told About Vitamins Wrong?

Author: Dr. Stephen Chaney

 

man searching with magnifying glassI am a scientist and a professor. I taught medical students for 40 years. I believe in evidence based medicine. Why would I tell you that many of the clinical trials about the impact of individual nutrients on your health are misleading?

Let me start by sharing a story that I used to tell every new graduate student in my lab. The story goes like this: There is this drunk on the sidewalk, on his hands and knees under a lamppost, just groping around. A policeman comes up to him and says, “What are you doing?” The drunk says, “I’m looking for my housekeys.” The policeman gets down on his hands and knees and he looks too, and finally he says, “I can’t find them anywhere. Are you sure you lost them here?” To which the drunk relies, “Nope, I lost them over there, but the light’s better here.”

The point I was trying to make is that we can only do experiments where the light is good. But the questions we sometimes want to ask are over in the corner, where we can’t really shine the light on it directly. It’s often difficult to look in the right place and/or to ask the right questions.

That’s particularly the case with holistic approaches because holistic approaches, by their very nature, are multi-factorial. You have multiple variables that you’re trying to change at one time. For example, you might want to optimize weight, exercise, vitamins, minerals, and essential fatty acids if you’re trying to look at a healthy lifestyle.

But, in the 21st-century, studies generally focus on individual nutrients or individual drugs in an intervention, placebo-controlled trial. This is considered the “Gold Standard” for evidence based medicine. However, it’s very difficult to evaluate holistic approaches with that kind of study.

 

The Whole Is Greater Than The Parts

internationally renowned expert sessionOne of the examples that I love to use, because it really made an impression on me as a young scientist, occurred at an International Cancer Symposium I attended more than 30 years ago.

I attended a session in which an internationally renowned expert was giving his talk on colon cancer. He said, “I can show you, unequivocally, that colon cancer risk is significantly decreased by a lifestyle that includes a high-fiber diet, a low-fat diet, adequate calcium, adequate B-vitamins, exercise and weight control. But I can’t show you that any one of them, by themselves, is effective.”

The question that came to me as I heard him speak was: “What’s the message that a responsible scientist or responsible health professional should be giving to their patients or the people that they’re advising?” You’ve heard experts saying: “Don’t worry about the fat” “Don’t worry about calcium.” “Don’t worry about B-vitamins.” “Don’t worry about fiber.” “None of them can be shown to decrease the risk of colon cancer.”

Is that the message that we should be giving people? Or should we really be saying what that doctor said many years ago – that a lifestyle that includes all those things significantly decreases the risk of colon cancer?

 

Are Clinical Trials Misleading?

 

clinical trialsA recent paper about how to best evaluate the relationships between nutrition and disease (Shao et al, European Journal of Nutrition, DOI: 10.1007/s00394-017-1460-9) caught my attention. This paper, written by a team of 10 international experts, was a summary of key findings from a recent international meeting of the Council for Responsible Nutrition.

The paper started out by reviewing the strengths of clinical studies in which the effect of a single intervention on a health outcome is evaluated in a double-blind, placebo controlled clinical study; something they referred to as a reductionist approach.

  • A reductionist approach is ideal for evaluating the effect of drug candidates on disease outcomes. That is because:
    • Everyone in the study already has the disease.
    • The drug is meant to be used by itself.
    • It is easy to measure outcomes. The drug either has an effect on the disease, or it doesn’t.
  • A reductionist approach has also been valuable in defining the role of nutrients in preventing deficiency diseases. That is because, in the words of the authors:
    • “A simple cause-effect relationship exists between a particular nutrient and a specific deficiency disease.
    • Symptoms of a specific nutrient deficiency can be explained in terms of the role played by the respective nutrient.
    • Providing the nutrient in the diet can prevent, and in many cases, reverse, the deficiency disease.”

However, the authors went on to say that the use of the reductionist approach to study effect of nutrients on optimal health or holistic approaches to health often has led to misleading results. They characterized these studies as often “leading down a rabbit hole.”

For example, the authors said: “In an effort to uncover the magic bullet, scientists inappropriately studied nutrients in a drug-like context. Unlike drugs, nutrients do not function in isolation and have beneficial effects on multiple tissues and organ systems.”

The authors concluded by saying that if we want to truly understand the role of nutrients on health outcomes, we need to focus on holistic studies in which the effect of multiple nutrients on multiple health outcomes are evaluated.

 

Clinical Trials That Have Mislead Us

 

I realize that the report I just described is conceptual. It’s difficult to wrap your mind around. To better understand how clinical trials employing a reductionist approach can often mislead us, let’s look at some specific examples comparing holistic studies to reductionist studies.

dash dietHealthy diets: Healthy diets have a significant impact on health, but it is not possible to show that individual components of those diets are beneficial: In previous issues of “Health Tips From the Professor,” I have discussed the Mediterranean and DASH diets. I have shared studies showing that the Mediterranean diet dramatically reduces the risk of heart disease, diabetes, cognitive decline, and some forms of cancer. However, you would be hard pressed to show that individual components of the Mediterranean diet have a significant impact on these health outcomes.

Similarly, the DASH diet is as effective as drugs at controlling blood pressure (Moore et al, Hypertension, 38: 155-158, 2001 ). Other than sodium restriction, you would also be hard pressed to show that the individual components of the DASH diet exert a significant effect on blood pressure.

Supplements That Are Going to Kill You: Individual nutrients can sometimes have adverse effects on your health. Those reports generate a lot of negative press, but the adverse effects usually disappear when those nutrients are consumed along with nutrients that complement their effect on whole body metabolism.

Here are two examples of the negative press that you may have heard about the dangers of supplementation, but what the studies actually showed is that a holistic approach to supplementation was superior to supplementation with individual supplements.

For example, there was something called the Iowa Women’s Health Study that got some negative press in 2011 (Mursu et al, Archives of Internal Medicine, 171:1625-1633, 2011). This is one of those studies that led to headlines saying: “Vitamins can kill you.”

The study did show a slight increase in mortality in people who consumed high-dose vitamin B6 or high-dose folic acid by themselves. But in that same study, people who were taking high-dose B complex containing both B6 and folic acid in balance had no increase in mortality.

Another example is vitamin E and prostate cancer. You probably saw the headlines, which said: “Vitamin E increases the risk of prostate cancer.” Those headlines were based on a study published in the Journal of American Medical Association in 2011 (J Klein et al, Journal of the American Medical Association, 306: 1549-1556, 2011). However, in that same study the people who were taking vitamin E and selenium (two nutrients that work together synergistically) had no increase in cancer risk.

There is a good biochemical rationale for those results. Vitamin E converts some reactive oxygen species to peroxides, which are quite dangerous themselves. Selenium is part of an enzyme that converts peroxides to water. Together, vitamin E and selenium convert reactive oxygen species (free radicals) to something that is completely harmless. By itself, vitamin E does only half the job.

Holistic Approaches to Supplementation: The same appears to be true if you look at holistic approaches to supplementation rather than holistic approach to supplementationsupplementing with individual nutrients. A study done by Dr. Gladys Block and published in Nutrition Journal in 2007 (Block et al, Nutrition Journal 2007,6:30 doi: 10.1186/1475-2891-6-30) looked at a holistic approach to supplementation for the very first time.

She compared people who were taking multiple supplements, typically a multivitamin, extra antioxidants, extra B vitamins, carotenoids, fish oil and probiotics; people who were taking only a multivitamin; and people who were using no supplements whatsoever over a 20-year period.

The results were dramatic. The holistic supplement users had one-third the prevalence of angina, heart attacks and congestive heart failure and one-quarter the prevalence of diabetes compared to the other two groups. In contrast, reductionist studies looking at the effect of those nutrients individually have generally been inconclusive.

So just like a holistic approach to health, a holistic approach to supplementation appears to be superior to using individual supplements. This is a small study, but it is an example of the kinds of studies that need to be done in the future, if we are to truly understand the role of holistic approaches for optimizing our health.

 

The Bottom Line

Studies in which the effect of a single intervention on health outcomes is evaluated in a double-blind, placebo-controlled clinical study is considered the “Gold Standard” for evidence based medicine. A recent report has questioned the value of this kind of study in defining the impact of holistic approaches on health outcomes.

  • The authors concluded that the “Gold Standard” of clinical studies, which they referred to as a reductionist approach:
    • Was ideal for evaluating the effect of drugs on preventing or treating diseases.
    • Has been well suited for evaluating the role of individual nutrients in preventing deficiency diseases.
    • Was not well suited for evaluating the role of holistic approaches on health outcomes.
    • Was not well suited for evaluating the role of nutrients for promoting optimal health.
  • The authors concluded by saying that if we want to truly understand the role of nutrients on health outcomes, we need to focus on holistic studies in which the effect of multiple nutrients on multiple health outcomes are evaluated.
  • I shared three examples illustrating cases in which holistic approaches were more accurate than reductionist studies:
    • Healthy diets have a significant impact on health, but it is not possible to show that that individual components of those diets are beneficial.
    • Individual nutrients can sometimes have adverse effects on your health, but the adverse effects disappear when those nutrients are consumed along with nutrients that complement their effect(s) on whole body metabolism.
    • A holistic approach to supplementation can have a significant, beneficial effect on health outcomes, but it is difficult to show any benefit from individual nutrients included in that holistic approach to supplementation.
  • For more details, read the article above.

 

These statements have not been evaluated by the Food and Drug Administration. This information is not intended to diagnose, treat, cure or prevent any disease.

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Comments (2)

  • Alayne Campbell

    |

    Very informative, A good yardstick to measure by.

    How do I get a copy of your suggestions for those on kemotherapy?

    Reply

    • Dr. Steve Chaney

      |

      Dear Alayne,
      I am not a medical doctor, so I do not comment on specific medical cases. If you are talking about nutritional supplements, a general rule of thumb is to space supplements and chemotherapy drugs so that they are not present in the bloodstream at the same time. This usually involves a day or two window on either side of chemotherapy during which supplements are not taken. For more specific recommendations, consult your doctor and/or your pharmacist.
      Dr. Chaney

      Reply

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Latest Article

Should You Avoid Sugar Completely?

Posted October 24, 2017 by Dr. Steve Chaney

Is It The Sugar, Or Is It The Food?

Author: Dr. Stephen Chaney

 

Should we avoid sugar completely?  Almost every expert agrees that Americans should cut down on the amount of sugar we are consuming. However, for some people this has become a “sugar phobia”. They have sworn that “sugar shall never touch their lips”. Not only do they avoid sugar sweetened sodas and junk food, but they also have become avid label readers. They scour the label of every food they see and reject foods they find any form of sugar listed as an ingredient. Is this degree of sugar avoidance justified?

 

Should We Avoid Sugar to Keep it From Killing Us?

 

Let me add some perspective:

  • If you just take studies about the dangers of sugar at face value, sugar does, indeed, look dangerous. Excess sugar consumption is associated with increased risk of obesity, diabetes, and heart disease. However, when you look a little closer, you find that most of these studies have been done by looking at the correlation of each of these conditions with sugar sweetened beverage consumption (sodas and fruit juices).

A few studies have looked at the correlation of obesity and disease with total “added sugar” consumption. However, 71.6% of added sugar in the American diet comes from sugar sweetened beverages and junk food. None of the studies have looked at the sugar from healthy foods like fruits, vegetables, and whole grains. That’s because there is ample evidence that these foods decrease the risk of obesity, diabetes, and heart disease.

  • For example, if apples had a nutrition label, it would list 16 grams of sugar in a medium 80 calorie apple, which corresponds to about 80% of the calories in that apple. The sugar in an apple is about the same proportion of fructose and glucose found in high fructose corn syrup. Apples are not unique. The nutrition label would read about the same on most other fruits. Does that mean you should avoid sugar from all fruits? I think not.

Avoid Sugar or Avoid Certain Foods

 

avoid sugar from junk foodsThe obvious question is: “Why are the same sugars, in about the same amounts, unhealthy in sodas and healthy in fruits?” Let’s go back to those studies I just mentioned—the ones that are often used to vilify sugars. They are all association studies, the association of sugar intake with obesity and various diseases.

The weakness of association studies is the association could be with something else that is tightly correlated with the variable (sugar intake) that you are measuring. Could it be the food that is the problem, not the sugar?

If we look at healthy foods (fruits, vegetables, whole grains) they are chock full of vitamins, minerals, phytonutrients, fiber, and (sometimes) protein. Fiber and protein slow the absorption of sugar into the bloodstream. As a result, blood sugar levels rise slowly and are sustained at relatively low levels for a substantial period of time.

In sodas there is nothing to slow the absorption of blood sugar. You get rapid rise in blood sugar followed by an equally rapid fall. The same is true of junk foods consisting primarily of sugar, refined flour and/or fat.  Avoid sugar from those types of foods.

Another consideration is something called caloric density. Here is a simple analogy. I used to explain the concept of caloric density to medical students in my teaching days. There are about the same number of calories in a 2-ounce candy bar and a pound of apples (around 278 in the 2-ounce candy bar and 237 in a pound of apples). You can eat a 2-ounce candy bar and still be hungry. If you eat a pound of apples you are done for a while. In this example, the 2-ounce candy bar had a high caloric density (a lot of calories in a small package). Perhaps a more familiar terminology would be the candy bar was just empty calories.

Are Sodas and Junk Foods Killing Us?

avoid sugar from candyPutting all that together, you can start to understand why the foods the sugars are in are more important than the sugars themselves. When you consume sugars in the form of sugar sweetened beverages or sugary junk foods, your appetite increases. We don’t know for sure whether it is the intense sweetness of those foods, the rapid increase and fall in blood sugar, or the high caloric density (lots of calories ina small package) that makes us hungrier. It doesn’t matter. We crave more food, and it isn’t usually fruits, vegetables, and complex carbohydrates we crave. It’s more junk. That sets in motion a predictable sequence of events.

  • We overeat. Those excess calories are stored as fat and we become obese. [Note: The low carb enthusiasts will tell you our fat stores come from carbohydrates alone. That is incorrect. All excess calories, whether from protein, fat, or carbohydrate, are stored as fat.]
  • It’s not just the fat you can see (belly fat) that is the problem. Some of that fat builds up in our liver and muscles. This sets up an unfortunate sequence of metabolic events.
  • The fat stores release inflammatory cytokines into our bloodstream. That causes inflammation. Inflammation increases the risk of many diseases including heart disease and cancer.
  • The fat stores also cause our cells to become resistant to insulin. That reduces the ability of our cells to take up glucose, which leads to hyperglycemia and type 2 diabetes. [Note: The low carb enthusiasts will tell you carbohydrates cause type 2 diabetes. That is also incorrect. It is our fat stores that cause insulin resistance and type 2 diabetes. Our fat stores come from all excess calories, not just excess calories from carbohydrates.]
  • Insulin resistance also causes the liver to overproduce cholesterol and triglycerides and pump them into the bloodstream. That increases the risk of heart disease.
  • Sugar sweetened beverages and sugary junk foods also displace healthier foods from our diet. That leads to potential nutrient shortfalls that can increase our risk of many diseases.

However, none of this has to happen. The one thing that every successful diet has in common is the elimination of sodas, junk foods, fast foods and convenience foods. You should avoid sugar from those foods as much as possible. Once you eliminate those from your diet,you significantly enhance your chances of being at a healthy weight and being healthy long term.

 

What About Protein Supplements And Similar Foods?

Of course, the dilemma is what you, as an intrepid label reader, should do about protein supplements, meal replacement bars, or snack bars. They are supposed to be healthy, but the label lists one or more sugars. Even worse, the sugar content is higher than your favorite health guru recommends.  So, should you avoid sugar from supplements and the like?

In this case, a more useful concept is glycemic index, which is a measure of the effect of the food on your blood sugar levels. Healthy foods like apples may have a high sugar content, but they havea low glycemic index.

avoid sugar and consume protein to slow absorbptionThe same is true for the protein supplements and bars you are considering. Rather than looking at the sugar content, you should be looking for the term “low glycemic” on the label. That means there is enough fiber and protein in the food to slow the absorption of sugar into the bloodstream and stabilize your blood sugar levels.

What Does This Mean For You?

Don’t misunderstand me. I am not advocating for unlimited consumption of sugar. We should work on ways to avoid sugar or reduce the amount of sugar in our diet. On the other hand, we don’t need to become so strict that we and our family need to eat foods that taste like cardboard. We also don’t want to replace natural sugars with artificial sweeteners. I have warned about the dangers of artificial sweeteners previously.

We can go a long way towards reducing sugar by just eliminating sodas, other sugar sweetened beverages, junk foods, fast foods, convenience foods, and pastries from our diet. When considering fast foods and convenience foods, we should check the label for hidden sugar. For example, some Starbucks drinks are mostly sugar. When considering foods that are supposed to be healthy, we should look for the term “low glycemic” on the label.

So we don’t have to avoid sugar completely, but we should reduce sugar from sugar sweetened beverages and junk food.

 

The Bottom Line

 

We need to keep warnings about the dangers of sugar in perspective:

  • The studies showing that sugar consumption leads to obesity, diabetes, and heart disease have all been done with sodas and junk foods.
  • Many fruits have just as much sugar as a soda. They also contain about the same proportion of fructose and glucose as high fructose corn syrup. Yet we know fruits are good for us.
  • Diets rich in fruits, vegetables and whole grains decrease our risk of obesity, diabetes, and heart disease.
  • That is because the sugar in whole foods is generally present along with fiber and protein, which slows the absorption of sugar and prevents the blood sugar spikes we get with sodas and junk foods.
  • In the case of prepared foods like protein supplements, you should look for “low glycemic” on the label rather than sugar content. Low glycemic means that there is enough fiber and protein in the product to slow the absorption of sugar and prevent blood sugar spikes.
  • Don’t misunderstand me. I am not advocating for unlimited consumption of sugar. We should all work on ways to avoid sugar from junk foods or to reduce the amount of sugar in our diet. On the other hand, we don’t need to become so strict that we and our family need to eat foods that taste like cardboard. We also don’t want to replace natural sugars with artificial sweeteners.
  • We can go a long way towards reducing sugar by just eliminating sodas, other sugar sweetened beverages, junk foods, fast foods, convenience foods, and pastries from our diet. When considering fast foods and convenience foods, we should check the label for hidden sugar. When considering foods that are supposed to be healthy, we should look for the term “low glycemic” on the label.

For more details, read the article above.

 

These statements have not been evaluated by the Food and Drug Administration. This information is not intended to diagnose, treat, cure or prevent any disease.

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