Study suggests that popular diet regimen may have adverse effect on body's restorative capacity
Even as low-carbohydrate/high-protein diets have proven successful at helping individuals rapidly lose weight, little is known about the diets' long-term effects on vascular health.
Now, a study led by a scientific team at Beth Israel Deaconess Medical Center (BIDMC) provides some of the first data on this subject, demonstrating that mice placed on a 12-week low carbohydrate/high-protein diet showed a significant increase in atherosclerosis, a buildup of plaque in the heart's arteries and 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, as might occur during a heart attack.
Described in today's Online Version of the Proceedings of the National Academy of Sciences (PNAS), the study also found that standard markers of cardiovascular risk, including cholesterol, were not changed in the animals fed the low-carb diet, despite the clear evidence of increased vascular disease.
"It's very difficult to know in clinical studies how diets affect vascular health," says senior author Anthony Rosenzweig, MD, Director of Cardiovascular Research in BIDMC's CardioVascular Institute and Professor of Medicine at Harvard Medical School. "We, therefore, tend to rely on easily measured serum markers [such as cholesterol], which have been surprisingly reassuring in individuals on low-carbohydrate/high-protein diets, who do typically lose weight. But our research suggests that, at least in animals, these diets could be having adverse cardiovascular effects that are not reflected in simple serum markers."
Rosenzweig and his coauthors found that the increase in plaque build-up in the blood vessels and the impaired ability to form new vessels were associated with a reduction in vascular progenitor cells, which some hypothesize could play a protective role in maintaining vascular health.
"A causal role for these cells has not yet been proven, but this new data is consistent with the idea that injurious stimuli may be counterbalanced by the body's restorative capacity," he explains. "This may be the mechanism behind the adverse vascular effects we found in mice that were fed the low-carb diets."
The study's first author Shi Yin Foo, MD, PhD, a clinical cardiologist in the Rosenzweig laboratory at BIDMC, first embarked on this investigation after seeing heart-attack patients who were on these diets - and after observing Rosenzweig himself following a low-carbohydrate regimen.
"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 Foo. "Tony would counter by noting that there were no controls for my observations."
"Finally," adds 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."
The investigators proceeded to study a mouse model of atherosclerosis. These "ApoE" mice were fed one of three diets: a standard diet of mouse "chow" (65 percent carbohydrate; 15 percent fat; 20 percent protein); a "Western diet" in keeping with the average human diet (43 percent carbohydrate; 42 percent fat; 15 percent protein; and 0.15 percent cholesterol); or a low-carb/high-protein diet (12 percent carbohydrate; 43 percent fat; 45 percent protein; and 0.15 percent cholesterol).
"We had a diet specially made that would mimic a typical low-carb diet," explains Foo. "In order to keep the calorie count the same in all three diets, we had to substitute a nutrient to replace the carbohydrates. We decided to substitute protein because that is what people typically do when they are on these diets."
The scientists then observed the mice after six weeks, and again at 12 weeks. Consistent with experience in humans, the mice fed the low-carb diet gained 28 percent less weight than the mice fed the Western diet. However, further probing revealed that the animals' blood vessels exhibited a significantly greater degree of atherosclerosis, as measured by plaque accumulation: 15.3 percent compared with 8.8 percent among the Western diet group. (As expected, the mice on the chow diet showed minimal evidence of atherosclerosis compared with either of the other two groups.)