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Low-Carb, High-Protein Diet Blues

These Diets May Be Bad for Vascular Health

Low-carbohydrate, high-protein diets may help people to lose weight quickly, but little is known about the diets' long-term effects on vascular health.

A study in mice led by a BIDMC scientific team sheds some light on this subject.

The study's first author, Shi Yin Foo, MD, PhD, a clinical cardiologist in the laboratory of Anthony Rosenzweig, MD, began the research after seeing heart-attack patients on low-carb diets.

She also noticed that Dr. Rosenzweig, who is director of cardiovascular research at BIDMC's CardioVascular Institute, following a low-carb, high-protein diet.

"Over lunch, I'd ask Tony how he could eat that food and would tell him about the last low-carb patient I'd admitted to the hospital," says Dr. Foo. "Tony would counter by noting that there were no controls for my observations."

"Finally," adds Dr. Rosenzweig, "I asked Shi Yin to do the mouse experiment-so that we could know what happens in the blood vessels and so that I could eat in peace!"

Controlled Experiment

Mice placed on a 12-week, low-carbohydrate, high-protein diet showed a significant increase in atherosclerosis, which causes a buildup of plaque in the heart's arteries and is a leading cause of heart attack and stroke.

The findings also showed that the diet led to an impaired ability to form new blood vessels in tissues deprived of blood flow, which can occur during a heart attack.

Surprisingly, the study found that more common signs of cardiovascular risk, including cholesterol, were unchanged in the animals on the low-carb, high-protein diet, despite clear evidence of increased vascular disease.

The study involved mice that were fed one of three diets:

  • Mouse chow diet (65% carbs, 15% fat and 20% protein)
  • Western or average human diet (43% carbs, 42% fat, 15% protein and 0.15% cholesterol)
  • Low-carb/high-protein diet (12% carbs, 43% fat, 45% protein and 0.15% cholesterol)

After 12 weeks, the mice on the low-carb, high-protein diet gained 28% less weight than the mice on the Western diet, but they showed more signs of atherosclerosis: 15.3% compared with 8.8% among the Western diet group. As expected, the mice on the chow diet showed little evidence of atherosclerosis compared with the other two groups.

"Our next question was, 'Why do the low-carb, high-protein mice have such an increase in atherosclerosis?' " says Dr. Foo.

Reasons for the Results

She and her coauthors measured the usual signs of vascular disease, including the animals' cholesterol and triglyceride levels, oxidative stress, insulin and glucose, as well as levels of some inflammatory cytokines. But there was little or no difference in measurements for the mice on all three diets.

Dr. Foo then wondered whether the animals' ability to heal could be contributing to the difference. So the researchers looked at the animals' counts for EPC (endothelial or vascular progenitor) cells. These cells, which come from bone marrow, can help vessel regrowth and repair following injury.

According to Dr. Rosenzweig, the researchers found that, after only two weeks, measures of EPC cells dropped by 40% among the mice on the low-carb, high-protein diet.

"Understanding the mechanisms responsible for these effects, as well as the potential restorative capacity that may counteract vascular disease, could ultimately help guide doctors in advising their patients," explains Dr. Rosenzweig. "This issue is particularly important given the growing epidemic of obesity and its adverse consequences. For now, it appears that a moderate and balanced diet, coupled with regular exercise, is probably best for most people."

While Dr. Rosenzweig cautions that this research is still in its infancy, he did report on one definitive outcome: "These results succeeded in getting me off the low-carb diet."

In addition to Rosenzweig and Foo, study coauthors include BIDMC investigators Joanna Wykrzykowska and Christopher J. Sullivan, and Massachusetts General Hospital investigators Eric R. Heller, Jennifer J. Manning-Tobin, Kathryn J. Moore and Robert E. Gerszten. The study was published in the online version of the Proceedings of the National Academy of Sciences (PNAS) in August 2009.

Contact Information

CardioVascular Institute at
Beth Israel Deaconess Medical Center
330 Brookline Avenue
Boston, MA 02215