Interview with Richard J. Johnson, MD, about his recently published book

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In this month’s issue, ASN Kidney News editorial board member Edgar Lerma interviewed Richard J. Johnson, MD, Temple Hoyne Buell and NKF of Colorado Endowed Professor of Medicine, and chief, division of renal diseases and hypertension at the University of Colorado, Denver, about his recently published book “The Sugar Fix: The High-Fructose Fallout That’s Making you Fat and Sick.”

Your book, “The Sugar Fix: The High-Fructose Fallout That’s Making You Fat and Sick,” was recently published. It appears that your book is intended for a lay audience. Do you think that it would still be useful for health care providers, especially nephrologists?

Yes, it is written scientifically and quotes lots of studies, but it is geared for a lay audience that does not know medical language. I think there is something there for everyone.

How did you develop this interest in fructose?

We were aware that the administration of fructose could cause metabolic syndrome in rats. We also knew that mice lacking endothelial nitric oxide also develop features of metabolic syndrome. Finally, we knew that fructose raises uric acid levels, and that raising uric acid in the rat could induce endothelial dysfunction. Thus, we decided to test whether or not uric acid might have a role in fructose-induced metabolic syndrome.

What is the link between fructose and kidney disease, hypertension, and diabetes?

Fructose appears to induce kidney disease, hypertension, and metabolic syndrome via specific metabolic effects that are independent of energy intake, as these syndromes are not observed in rats fed the same amount of glucose. We believe this is due to the unique ability of fructose to cause ATP depletion and uric acid generation within the cell. In turn, raising intracellular uric acid results in a rise in serum uric acid and also induces intracellular oxidative stress, inhibits nitric oxide, and activates inflammatory and vasoconstrictive pathways.

Aside from what we already know about the link between uric acid and kidney disease (gouty nephropathy, chronic tubulointerstitial nephritis, etc.), what new associations has your research discovered?

There are more than 3500 articles to date showing a strong relationship between uric acid and obesity, heart disease, hypertension, stroke, kidney disease, and other conditions. In fact, a number of studies have confirmed that people with elevated serum uric acid are at risk for high blood pressure, even if they otherwise appear to be perfectly healthy.

Uric acid levels among Americans have risen significantly since the early half of the 20th century. In the 1920s, average uric acid levels were about 3.5 mL/dL. By 1980, average uric acid levels had climbed into the range of 6.0 to 6.5 mL/dL and are probably much higher now.

Our new work is opening new roles for uric acid in metabolic syndrome, obesity, and hypertension. We have also found that fructose ingestion can induce all features of metabolic syndrome, including fatty liver and leptin resistance. Our studies suggest that the metabolic syndrome may be an actual disease.

What are the most common sources of fructose?

The most common sources of fructose are from added sweeteners such as sucrose (which contains 50 percent fructose and 50 percent glucose bound as a disaccharide) and high fructose corn syrup (HFCS) (containing 55 percent fructose and 45 percent glucose as monosaccharides). The major sources of these sweeteners are soft drinks, but certainly desserts, pastries, jellies, fruit drinks, etc., often are loaded with sugar. HFCS is also added to many foods one would not naturally consider sweet, but the amounts added are just enough to provide a slightly sweet taste. Fruits and honey also contain fructose. Most fruits have approximately 8 g of fructose and hence are a relatively minor source; they also contain many good nutrients including vitamin C, antioxidants, potassium, and fiber (Figure 1). Hence, natural fruit ingestion does not increase the risk for metabolic syndrome, whereas this is not true for added sugars and fruit drinks and fruit juices, where the concentration and amount of fructose is higher.

Figure 1.
Figure 1.

Amount of fructose in various fruits

Citation: Kidney News 2, 10

So, is fructose just as bad as glucose? Please discuss the “glycemic index” and “fructose index.”

Glucose is not bad unless you are diabetic or severely insulin-resistant, as it is elevations in blood glucose and not dietary glucose that appear to drive obesity and diabetes and its complications. While ingesting glucose or starch stimulates insulin, it is not insulin stimulation that is bad, but rather insulin resistance. Fructose induces insulin resistance, but glucose does not. We have suggested the use of a fructose index, which is much more informative than a glycemic index. The reason the glycemic index correlates with obesity is because one of the principal foods with a high glycemic index is sugar. However, it is the glucose component driving the glycemic index of sugar, but it is the fructose component that is responsible for its metabolic effects.

I commonly encounter this question in my CKD patients: “Is soda bad for my kidneys?” What is your take on recent studies that have focused on this subject matter that have provided contradictory findings?

Today, 55 percent of sweeteners used in food and beverage manufacturing are made from corn, and the number one source of calories in America is soda, in the form of high fructose corn syrup.

Food and beverage manufacturers began switching their sweeteners from sucrose to corn syrup in the 1970s when they discovered that HFCS was not only far cheaper to make, it’s about 20 percent sweeter than conventional table sugar that has sucrose.

HFCS contains the same two sugars as sucrose but is more metabolically risky to you, due to its chemical form.

The fructose and the glucose are not bound together in HFCS, as they are in table sugar, so your body doesn’t have to break it down. Therefore, the fructose is absorbed immediately, going straight to your liver.

Soda will put on weight, induce fatty liver, and cause insulin resistance. This is normally not a good thing. However, some dialysis patients are cachectic, and stimulating and increasing fat stores in these patients may not be a bad thing. Clearly, for an otherwise healthy individual, avoid excess sugar!

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