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The Quagmire of Nutritional Studies

Want to boost nitrate intake? Set aside your academic journals and try a big salad made from arugula, spinach and romaine lettuce.

This article was first published in


There are roughly 9,000 research papers published annually in the 75 or so journals dedicated to nutrition. That translates to about two dozen a day. Why is this staggering amount of nutritional research carried out by scientists around the world? The simple answer is so that we can determine what to eat and what not to eat for a healthier, longer life.

The amount of data produced is overwhelming, as is the challenge of filtering out information of practical use. Papers may describe high quality research that comfortably passes peer-review but has dubious real-world application. That raises questions about which studies merit increasingly scarce research funds. A look at two papers, both published in proper peer-reviewed journals, illustrates this point.

The titles of these papers may be off-putting even to people comfortable with science: “ alters phenotypic expression in skeletal muscle of aged male and female mice” may sound as undecipherable as “ nitric oxide bioavailability and vascular responses to dietary nitrate supplementation.” Let’s try to demystify.

Both studies deal with aging, which is of interest to everyone because we all do it. Reluctantly. Any help in slowing the process is welcome.

As pointed out in the introduction of the first paper, extensive evidence backs the high consumption of fruits and vegetables to lower the risk of an early death, but what components in these foods are specifically responsible is not clear. Grapes, for example, contain at least 1,600 compounds! One of these, resveratrol, has been hypothesized to have an anti-aging effect based on its ability to neutralize free radicals associated with aging. But that is in cell culture. In animal models, doses that are potentially beneficial far exceed those that can be realistically achieved in the human diet. That’s why researchers decided to focus not on individual components but on a whole food. Well, almost a whole food. In this case, they decided on freeze-dried grape powder.

The focus was on muscle function, since it is known that aging is associated with sarcopenia, a progressive loss of muscle mass. Since all voluntary movements as well as the involuntary movements that control cardiac and digestive systems rely on skeletal muscle, an investigation of how a specific food such as grapes may affect muscle function is of interest.

That is why researchers fed male and female mice grape powder comparable to one and a half cups of grapes every day for 2.5 years, which is the approximate human equivalent of 80 years. They then looked for any changes in the expression of the 25 genes known to be associated with muscle strength. The conclusion was that changes in gene expression were indicative of beneficial effects especially in females whose muscle tissue began to resemble the male phenotype. An individual’s observable traits are referred to as their phenotype.

This was an elegant study to be sure and well carried out. But what are we to make of it?

First item to note is that humans are not giant mice and rodent data cannot be assumed to apply to people. And the researchers did not actually measure muscle strength; they just looked at gene expression that may be associated with muscle strength. Then there is the extreme improbability that a person will consume a cup and a half of grapes every day for 80 years, and furthermore, freeze-dried grapes may not be chemically equivalent to whole grapes.

What we are left with is a study of academic interest but no practical value except for supporting the well-established notion that fruit consumption is beneficial.

Let’s now turn to the second study. First item to note is that this was carried out not with mice but with human subjects. That right away puts it in a different category. Like the grape study, it explored the potential effects of a plant product, in this case beets. Not in a freeze-dried version, but as a juice consumed in realistic amounts.

Before elaborating further, we need to get acquainted with nitric oxide, an important neurotransmitter that makes blood vessels more flexible and allows for easier dilation that in turn lowers blood pressure. Reducing blood pressure is an important factor in reducing the risk of premature death. Nitric oxide is produced in the body from the amino acid arginine — but with age, the body’s ability to convert arginine to nitric oxide slows and there is greater reliance on an alternative pathway. This involves bacteria in saliva that convert nitrates into nitrites that in turn can be converted into nitric oxide in the stomach. From here nitric oxide can enter the bloodstream and relax blood vessels. Beetroot is high in nitrates — hence the interest in its effect on blood pressure.

Researchers enlisted 39 adults in the 18-30 age group and 36 in the 67-79 category. In terms of nutritional studies, these are numbers that can yield statistically significant results. In sequential two-week periods the subjects consumed either beetroot juice or beetroot juice from which nitrates had been removed. Then for another two weeks they used a mouthwash that reduces oral bacteria.

The regular juice resulted in an increase in blood levels of nitrate and nitrite, but interestingly the increase was substantially greater in the older age group! Somehow, their body sensed reduced production of nitrite from arginine and compensated by altering the microbiome in the mouth in favour of bacteria that convert nitrate to nitrite. The result was a reduction in blood pressure, an effect not seen with the “placebo” beetroot juice devoid of nitrates. Rinsing the mouth with the antiseptic mouthwash altered the diversity of the oral microbiome that in turn resulted in a reduction of how well blood vessels can expand and relax.

This time we have a study that is more than just of academic interest. Seniors can benefit from the dietary consumption of nitrates!

But before diving into the beetroot juice, let’s have a look at numbers. In this study, the subjects consumed two cups of the juice a day, furnishing 750 mg of nitrates. Unfortunately, that amount of juice also contains 40-50 grams of sugar. Way too much! Beetroot powders that contain less sugar are available, but they do not list their nitrate content, so as with most supplements, the consumer is at a loss.

Better to boost nitrate intake from vegetables. A big salad made from arugula, spinach and romaine lettuce can net about 400 mg of nitrate. That can have some impact on blood pressure and in addition supplies a range of antioxidants, vitamins and minerals.

Although the first study is interesting and well done, in my view, it produces very little bang for the buck. The second one does provide a bit of useful information about the effect of nitrates and oral bacteria on health. Frankly, I doubt that any of the thousands of nutritional papers published in the coming year will add significantly to what we already know about nutrition.


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